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Huang Y, Wang N, Ji X, Luo S, Gong L, Zhao C, Zheng G, Liu R, Zhang T. Apigenin ameliorates inflamed ulcerative colitis by regulating mast cell degranulation via the PAMP-MRGPRX2 feedback loop. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2025; 140:156564. [PMID: 40054174 DOI: 10.1016/j.phymed.2025.156564] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/08/2024] [Revised: 02/10/2025] [Accepted: 02/23/2025] [Indexed: 03/25/2025]
Abstract
PURPOSE The aim of this study was to investigate the therapeutic effect of API on UC via the regulation of PAMP-MRGPRX2-mediated mast cells (MCs) degranulation. BACKGROUND The pro-inflammatory positive feedback loop mediated by Mas-related G-protein-coupled receptor X2 (MRGPRX2) and its endogenous ligand, PAMP-12, is associated with ulcerative colitis (UC) progression. However, the therapeutic strategies that target MRGPRX2 in the treatment of UC are less reported. Apigenin (API), a natural flavonoid, can relieve inflammation. METHOD A dextran sodium sulfate (DSS)-induced mouse UC model was used to elucidate the therapeutic effects of API. Animal behavior assessment, serological assays, and histological analysis were performed in wild-type (WT) and MC MrgprB2-conditional knockout (CKO) mouse model. mRNA sequencing analysis, PCR, ELISA, and western blotting were performed in vitro and in vivo to elucidate the mechanism underlying the effect of API by a PAMP-12 triggered MC degranulation model. RESULTS MC degranulation via MrgprB2 was critical for the persistence of inflammation in colitis. API attenuated colonic tissue damage, splenomegaly, and myeloperoxidase (MPO) activity in the colonic tissues. It also ameliorated colonic crypt structure damage and inflammatory cell infiltration. Moreover, API suppressed MCs degranulation, and the level of carboxypeptidases A3 (CPA3), in DSS-induced colitis, thereby blocking the pro-inflammatory positive feedback loop induced by PAMP-MrgprB2. Lastly, API effectively inhibited PAMP-12-triggered mast cell degranulation by regulating Akt1/XBP-1S/CHOP/TXNIP and NF-κB/IL-1β signaling pathways. CONCLUSION API alleviates inflammatory symptoms in UC by suppressing PAMP-MRGPRX2/B2 mediated MC sustained degranulation feedback loop.
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MESH Headings
- Animals
- Mast Cells/drug effects
- Colitis, Ulcerative/drug therapy
- Colitis, Ulcerative/chemically induced
- Colitis, Ulcerative/metabolism
- Receptors, G-Protein-Coupled/metabolism
- Receptors, G-Protein-Coupled/genetics
- Apigenin/pharmacology
- Cell Degranulation/drug effects
- Mice
- Mice, Knockout
- Mice, Inbred C57BL
- Disease Models, Animal
- Male
- Dextran Sulfate
- Receptors, Neuropeptide/metabolism
- Feedback, Physiological/drug effects
- Nerve Tissue Proteins/metabolism
- Signal Transduction/drug effects
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Affiliation(s)
- Yihan Huang
- School of Pharmacy, Health Science Center, Xi'an Jiaotong University, Xi'an 710061, China
| | - Na Wang
- Department of Otolaryngology, Affiliated Hospital of North China University of Science and Technology, Tangshan 063000, China
| | - Xiaolan Ji
- School of Pharmacy, Health Science Center, Xi'an Jiaotong University, Xi'an 710061, China
| | - Shiqiong Luo
- School of Pharmacy, Health Science Center, Xi'an Jiaotong University, Xi'an 710061, China
| | - Ling Gong
- School of Pharmacy, Health Science Center, Xi'an Jiaotong University, Xi'an 710061, China
| | - Chenrui Zhao
- School of Pharmacy, Health Science Center, Xi'an Jiaotong University, Xi'an 710061, China
| | - Guodong Zheng
- School of Pharmacy, Health Science Center, Xi'an Jiaotong University, Xi'an 710061, China
| | - Rui Liu
- School of Pharmacy, Health Science Center, Xi'an Jiaotong University, Xi'an 710061, China.
| | - Tao Zhang
- School of Pharmacy, Health Science Center, Xi'an Jiaotong University, Xi'an 710061, China.
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2
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Li N, Shang X, Shi L, Li Y, Mao T, Wang Q, Li J, Peng G. Effects of three Chinese herbal therapies on gut microbiota and short-chain fatty acid metabolism in patients with mild, moderate, and severe ulcerative colitis: Multi-center, randomized, controlled trials. Int Immunopharmacol 2025; 152:114444. [PMID: 40088871 DOI: 10.1016/j.intimp.2025.114444] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2024] [Revised: 02/24/2025] [Accepted: 03/05/2025] [Indexed: 03/17/2025]
Abstract
BACKGROUND Traditional Chinese medicines, as a burgeoning field of medication, significantly alleviate ulcerative colitis (UC) by improving intestinal microbiota-metabolism. Our previous studies demonstrated the significant efficacy of Hudi Enteric-coated capsules (HDEC), Qingchang Wenzhong decoction (QCWZ), and Modified Wumei pill (MWMP) using a mouse model of colitis. However, the mechanism of these therapies through the modulation of microbiota-metabolism remains uncertain. OBJECTIVE Three multicenter randomized controlled trials were designed to explore the effects of three therapies on the microbiota-metabolism of UC patients with different severity. METHODS A total of 143 patients with different severities of UC were recruited from 10 hospitals. The clinical efficacy of HDEC for mild UC, QCWZ for moderate UC, and MWMP for severe UC (SUCs) was evaluated by colorectal Mayo scores and systemic inflammatory indicators. The 16S rRNA sequencing and metabolomics were used to analyze intestinal microbiota and metabolite profiles. RESULTS Three therapies used alone or combined with mesalazine (MS) were comparable to MS alone in improving Mayo scores and hematic inflammatory parameters. Microbial diversities and architectures of SUCs showed the greatest response to MWMP+MS than other medications, as reflected by the enriched Ruminococcus and Anaerostipes together with the reduced Enterococcus, Streptococcus, and Streptococcus anginosus. Furthermore, MWMP+MS boosted the production of the microbiota-derived short-chain fatty acids (SCFAs) of SUCs. These differential microbes and metabolites further displayed significant statistical relationships with clinical parameters. CONCLUSION Herbal therapies, especially MWMP+MS, effectively improve microbiota composition and SCFA metabolism, which correlates with the improvements of serum inflammatory markers and endoscopic findings in patients.
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Affiliation(s)
- Na Li
- Department of Immunology and Microbiology, School of Life Sciences, Beijing University of Chinese Medicine, Beijing, China
| | - Xuekai Shang
- Department of Immunology and Microbiology, School of Life Sciences, Beijing University of Chinese Medicine, Beijing, China
| | - Lei Shi
- Department of Gastroenterology, Dong Fang Hospital, Beijing University of Chinese Medicine, Beijing, China
| | - Yalan Li
- Department of Immunology and Microbiology, School of Life Sciences, Beijing University of Chinese Medicine, Beijing, China
| | - Tangyou Mao
- Department of Gastroenterology, Dong Fang Hospital, Beijing University of Chinese Medicine, Beijing, China
| | - Qing Wang
- Department of Immunology and Microbiology, School of Life Sciences, Beijing University of Chinese Medicine, Beijing, China
| | - Junxiang Li
- Department of Gastroenterology, Dong Fang Hospital, Beijing University of Chinese Medicine, Beijing, China.
| | - Guiying Peng
- Department of Immunology and Microbiology, School of Life Sciences, Beijing University of Chinese Medicine, Beijing, China.
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3
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Kakati N, Paul N, Dubey S, Mahanta J, Lakshmi AR, Banerjee T, Bandyopadhyay D. Microrheology of Ionic Liquid Doped Mucus for an Efficient Delivery of Protein-Based Oral Drugs. SMALL (WEINHEIM AN DER BERGSTRASSE, GERMANY) 2025; 21:e2500403. [PMID: 40033884 DOI: 10.1002/smll.202500403] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/10/2025] [Revised: 02/20/2025] [Indexed: 03/05/2025]
Abstract
Developing protein-based drugs for oral administration is one of the most challenging aspects of research due to their low stability and inability to permeate through intestinal mucus barrier. Recent studies suggest that the ionic liquids (ILs) can combine with protein-based drugs to improve stability and mucus-penetration capabilities. However, the interactions among protein-based drugs, ILs, and mucin are rather unknown, which can play a pivotal role in such drug delivery. The present work unveils the molecular mechanisms of the delivery of protein-based drugs, with the help of microrheology experiments and density functional theory (DFT) simulations. The study employs a model mesoscale drug delivery system composed of an IL, mucin, and bovine serum albumin (BSA) as a model drug. In particular, following the microrheological changes of such drug formulations helps in tracing the molecular interactions such as electrostatic, van der Waals, steric, and hydrogen bonds, at the various stages of BSA, mucin, and IL assemblage. The results are corroborated by the morphological studies using atomic force microscopy supplemented by microrheological studies using diffusing-wave-spectroscopy. A human intestine has also been simulated as a biomimetic in-vitro prototype to demonstrate stability and penetration of BSA through mucin in the presence of IL.
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Affiliation(s)
- Nayanjyoti Kakati
- Department of Chemical Engineering, Indian Institute of Technology Guwahati, Guwahati, Assam, 781039, India
| | - Nabendu Paul
- Department of Chemical Engineering, Maulana Azad National Institute of Technology, Bhopal, Madhya Pradesh, 462003, India
| | - Saurabh Dubey
- Centre for Nanotechnology, Indian Institute of Technology Guwahati, Guwahati, Assam, 781039, India
| | - Jiwajyoti Mahanta
- Department of Chemical Engineering, Indian Institute of Technology Guwahati, Guwahati, Assam, 781039, India
| | - Anushka Raj Lakshmi
- Department of Chemical Engineering, Indian Institute of Technology Guwahati, Guwahati, Assam, 781039, India
| | - Tamal Banerjee
- Department of Chemical Engineering, Indian Institute of Technology Guwahati, Guwahati, Assam, 781039, India
- Centre for the Environment, Indian Institute of Technology Guwahati, Guwahati, Assam, 781039, India
| | - Dipankar Bandyopadhyay
- Department of Chemical Engineering, Indian Institute of Technology Guwahati, Guwahati, Assam, 781039, India
- Centre for Nanotechnology, Indian Institute of Technology Guwahati, Guwahati, Assam, 781039, India
- Jyoti and Bhupat Mehta School of Health Sciences and Technology, Indian Institute of Technology Guwahati, Guwahati, Assam, 781039, India
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Westfall KM, Charles R, Steinhagen E. Diagnosis and Differentiation of Inflammatory Bowel Disease. Surg Clin North Am 2025; 105:217-232. [PMID: 40015813 DOI: 10.1016/j.suc.2024.09.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/01/2025]
Abstract
Differentiating Crohn's disease from ulcerative colitis may be a diagnostic challenge for clinicians due to overlapping features. However, the correct diagnosis may guide treatment options and considerations regarding surgery. This study reviews the common components of diagnostic evaluation of inflammatory bowel disease. Additionally, this article provides a basis of understanding for the more complex aspects of the disease to be discussed in subsequent studies.
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Affiliation(s)
- Kristen M Westfall
- Department of Surgery, Division of Colorectal Surgery, University Hospitals Cleveland Medical Center, 11100 Euclid Avenue, Cleveland, OH 44106, USA
| | - Ronald Charles
- Department of Surgery, Division of Colorectal Surgery, University Hospitals Cleveland Medical Center, 11100 Euclid Avenue, Cleveland, OH 44106, USA
| | - Emily Steinhagen
- Department of Surgery, Division of Colorectal Surgery, University Hospitals Cleveland Medical Center, 11100 Euclid Avenue, Cleveland, OH 44106, USA.
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5
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Qu YT, Ding JY, Pan W, Liu FR, Dong AL. Perspectives in clinical research on Azathioprine for steroid-dependent ulcerative colitis. Front Med (Lausanne) 2025; 12:1551906. [PMID: 40201324 PMCID: PMC11975918 DOI: 10.3389/fmed.2025.1551906] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/26/2024] [Accepted: 03/11/2025] [Indexed: 04/10/2025] Open
Abstract
This study explores the application of Azathioprine in the treatment of ulcerative colitis (UC) and the challenges associated with its long-term use. While short-term studies demonstrate the efficacy of Azathioprine in steroid-dependent UC, long-term data on its risks, including malignancies, infections, and chronic toxicity, remain insufficient. Furthermore, the impact of Azathioprine on patients' quality of life over extended periods is still unclear. The research highlights the importance of optimizing Azathioprine dosing based on genomic data, particularly through TPMT and NUDT15 genotyping, to minimize adverse effects. However, further research is needed to develop individualized treatment strategies that can improve efficacy and reduce toxicity. The identification of predictive biomarkers, through genomics and proteomics, is likely to play a crucial role in improving treatment precision by identifying patients who are most likely to benefit from Azathioprine therapy. Additionally, combining Azathioprine with biologic therapies (such as anti-TNF agents or integrin inhibitors) and interventions targeting the gut microbiome may enhance the drug's effectiveness while reducing reliance on steroids. Overall, large-scale clinical trials are urgently needed to evaluate the benefits and risks of these emerging therapies, ultimately supporting more personalized treatment approaches for steroid-dependent UC patients.
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Affiliation(s)
- Yuan-Ting Qu
- Department of Gastroenterology, Hongqi Hospital Affiliated to Mudanjiang Medical University, Mudanjiang, China
| | - Jia-Yuan Ding
- Department of Gastroenterology, Hongqi Hospital Affiliated to Mudanjiang Medical University, Mudanjiang, China
| | - Wei Pan
- Department of Gastroenterology, Hongqi Hospital Affiliated to Mudanjiang Medical University, Mudanjiang, China
| | - Fang-Rui Liu
- Department of Gastroenterology, Mudanjiang First People’s Hospital, Mudanjiang, China
| | - Ai-Lian Dong
- Department of Gastroenterology, Hongqi Hospital Affiliated to Mudanjiang Medical University, Mudanjiang, China
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6
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Biskup L, Semeradt J, Rogowska J, Chort W, Durko Ł, Małecka-Wojciesko E. New Interleukin-23 Antagonists' Use in Crohn's Disease. Pharmaceuticals (Basel) 2025; 18:447. [PMID: 40283885 PMCID: PMC12030181 DOI: 10.3390/ph18040447] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2025] [Revised: 03/10/2025] [Accepted: 03/19/2025] [Indexed: 04/29/2025] Open
Abstract
Crohn's disease (CD) is a chronic inflammatory condition of the digestive tract, driven by an imbalance in immune system regulation, where proinflammatory interleukin-23 (IL-23) plays an essential role. Selective new IL-23 inhibitors, including risankizumab, guselkumab, and mirikizumab, block the IL-23p19 subunit to inhibit the Il-23 action and alleviate inflammation in CD. This review explores the effectiveness, safety, and therapeutic potential of anti-IL-23 treatment in CD management. Risankizumab, guselkumab, and mirikizumab demonstrated considerable effectiveness in inducing clinical remission and promoting endoscopic healing in patients with moderately to severely active CD, including those refractory to anti-TNF therapies. Risankizumab showed favorable results in pivotal trials like ADVANCE, MOTIVATE, and FORTIFY, achieving remission rates of up to 45% and sustained inflammatory biomarkers normalization. Guselkumab and mirikizumab similarly demonstrated substantial efficacy in the induction and maintenance phases, with promising long-term results. The safety profiles of IL-23 inhibitors were favorable, with low rates of serious adverse events, including infections and malignancies. Selective new IL-23 inhibitors represent a targeted and effective therapeutic class for moderately to severely active CD, offering high clinical and endoscopic remission rates, and favorable safety outcomes. Continued research, particularly on long-term efficacy and the selection of patients based on inflammatory biomarkers, will help optimize their role in personalized treatment strategies for refractory CD.
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Affiliation(s)
| | | | | | | | | | - Ewa Małecka-Wojciesko
- Department of Digestive Tract Diseases, Medical University of Lodz, 90-419 Lodz, Poland
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7
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Moreau LA, Ford AC, Brookes MJ, Graca S, Guthrie E, Hartley S, Houghton L, Kemp K, Kennedy NA, McKenzie Y, Muir D, Loo Ow P, Probert C, Pryde E, Taylor C, Willis TA, Wright-Hughes A, Farrin AJ. Management of diarrhoea in patients with stable ulcerative colitis with low FODMAP diet, amitriptyline, ondansetron or loperamide: the MODULATE RCT. Health Technol Assess 2025:1-30. [PMID: 40079650 PMCID: PMC11931405 DOI: 10.3310/ghfe4871] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/15/2025] Open
Abstract
Background Many patients with ulcerative colitis report ongoing diarrhoea even when their disease is stable and in remission. Design MODULATE was a pragmatic, multicentre, seamless, adaptive, phase 2/3 open-label, parallel-group, multiarm multistage randomised controlled trial. Setting and participants People aged over 18 years with stable ulcerative colitis who had diarrhoea, recruited from secondary care sites in the United Kingdom. Interventions The control arm consisted of modified first-line dietary advice given to all patients with irritable bowel syndrome; the first interventional arm was amitriptyline, a tricyclic antidepressant, which at low doses slows colonic transit; the second intervention was loperamide, an antidiarrhoeal drug also thought to slow colonic transit; the third was ondansetron, an antiemetic thought to slow colonic transit; and the fourth was a diet low in fermentable oligo-, di-, and mono-saccharides and polyols, which is thought to reduce bloating and gas within the small intestine. All patients randomised to an interventional arm were to receive treatment for 6 months. Main outcome measures: Primary outcome measures Phase 2: Improvement in diarrhoea measured using the Gastrointestinal Symptom Rating Scale-irritable bowel syndrome questionnaire at 8 weeks post randomisation: improvement defined as those reporting minor discomfort from diarrhoea or less (scoring ≤ 2 on the diarrhoea subscale). Secondary outcome measures Phases 2 and 3: Measured at both 8 weeks and 6 months: Improvement in diarrhoea measured using the Gastrointestinal Symptom Rating Scale-irritable bowel syndrome. Blood for C-reactive protein, stool for faecal calprotectin at 6 months only, reviewing case notes for escalation of medical therapy for ulcerative colitis. Anxiety and depression, via the Hospital Anxiety and Depression Scale. Results The MODULATE trial opened in December 2021 and closed in January 2023. Of the eight secondary care sites that completed contracting, only four opened to recruitment during this time, and one person was randomised. Trial timelines coincided with the start of the COVID-19 pandemic, causing substantial delays and, ultimately, its early closure. During this time, the trial underwent two major redesign phases, enabling a fully remote participant pathway incorporating electronic consent, remote data capture, posted blood and stool sample kits for eligibility screening, delivery of the dietary intervention via telephone or video call platform, postage of trial investigational medicinal products directly to participants' homes and all trial follow-up appointments conducted via telephone. The second phase of redesign pushed the trial towards a fully decentralised model. However, this stage was not implemented due to the decision to close the trial early. Limitations The study was unable to recruit the necessary sample size, preventing the trial from progressing. The trial met with several challenges. The Trial Steering Committee's root cause analysis concluded that the pandemic was the leading factor in trial closure, especially regarding our ability to recruit both sites and participants. Conclusions Although the trial closed early and with insufficient participants to proceed with full statistical analysis, lessons were learnt that could potentially inform future remote trial design and decentralised participant pathways. Future work MODULATE was a commissioned call in response to a priority question identified by people living with ulcerative colitis. The question remains important and unanswered; trials to address it are needed. Given the recruitment difficulties we experienced, consideration should be given to conducting these in both primary and secondary care. Funding This synopsis presents independent research funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme as award number 17/33/03.
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Affiliation(s)
- Lauren A Moreau
- Clinical Trials Research Unit, University of Leeds, Leeds, UK
| | - Alexander Charles Ford
- Leeds Institute of Medical Research at St James's, Leeds Teaching Hospitals NHS Trust, Leeds, UK
| | | | - Sandra Graca
- Clinical Trials Research Unit, University of Leeds, Leeds, UK
| | - Elspeth Guthrie
- Leeds Institute of Health Sciences, University of Leeds, Leeds, UK
| | | | - Lesley Houghton
- Division of Gastroenterology and Surgical Sciences, Leeds Institute of Medical Research at St James's, University of Leeds, Leeds, UK
| | - Karen Kemp
- Manchester University NHS Foundation Trust, Manchester, UK
| | - Nicholas A Kennedy
- Royal Devon University Healthcare NHS Foundation Trust, UK/University of Exeter, Exeter, UK
| | | | - Delia Muir
- Clinical Trials Research Unit, University of Leeds, Leeds, UK
| | - Pei Loo Ow
- Clinical Trials Research Unit, University of Leeds, Leeds, UK
| | - Christopher Probert
- Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, UK
| | - Emma Pryde
- Patient and Public Engagement, UK/Crohn's and Colitis UK Research Champion, Leeds, UK
| | | | - Thomas A Willis
- Clinical Trials Research Unit, University of Leeds, Leeds, UK
| | | | - Amanda J Farrin
- Clinical Trials Research Unit, University of Leeds, Leeds, UK
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8
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Simeone S, Spagnuolo R, Cosco C, Tino E, Pagnotta R, Doldo P. Lived Experiences of Patients With Inflammatory Bowel Disease in Italy: A Phenomenological Investigation. Gastroenterol Nurs 2025; 48:116-127. [PMID: 40192751 DOI: 10.1097/sga.0000000000000853] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/15/2022] [Accepted: 06/13/2024] [Indexed: 05/17/2025] Open
Abstract
Inflammatory bowel disease is a type of chronic gastrointestinal inflammatory disease. The chronic nature of the disease, the severity of its symptoms, and its unpredictability make it comparable to cancers regarding both its influence on quality of life and the direct and indirect health costs. The impact of inflammatory bowel disease on daily life is well documented; however, despite the notable increase in the incidence of inflammatory bowel disease in recent years, the international literature still does not adequately take into account the perspective of patients and how they experience the disease in their daily lives. With Cohen's phenomenology method, we investigate the lived experience of people suffering from inflammatory bowel disease. Our sample included 21 participants with an average age of 47 years. Three main themes and related subthemes emerged: A "deep life change" with the subtheme of "self-isolation," being "invisibly sick," and "receiving the diagnosis" with the subtheme of "trust in health professionals." Understanding the lived experiences of people living with inflammatory bowel disease will aid in the development of educational programs and effective interventions.
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Affiliation(s)
- Silvio Simeone
- Silvio Simeone, PhD, RN is Assistant Professor, Department of Clinical and Experimental Medicine, Magna Graecia, University of Catanzaro, Catanzaro, Italy
- Rocco Spagnuolo, PhD, MD is Assistant Professor, Department of Health Sciences, Magna Graecia, University of Catanzaro, Catanzaro, Italy
- Cristina Cosco, MD, Department of Clinical and Experimental Medicine, Magna Graecia, University of Catanzaro, Catanzaro, Italy
- Elena Tino MD, Department of Clinical and Experimental Medicine, Magna Graecia, University of Catanzaro, Catanzaro, Italy
- Raffaele Pagnotta, RN, Department of Clinical and Experimental Medicine, Magna Graecia, University of Catanzaro, Catanzaro, Italy
- Patrizia Doldo, PhD, MD is Professor, Department of Clinical and Experimental Medicine, Magna Graecia, University of Catanzaro, Catanzaro, Italy
| | - Rocco Spagnuolo
- Silvio Simeone, PhD, RN is Assistant Professor, Department of Clinical and Experimental Medicine, Magna Graecia, University of Catanzaro, Catanzaro, Italy
- Rocco Spagnuolo, PhD, MD is Assistant Professor, Department of Health Sciences, Magna Graecia, University of Catanzaro, Catanzaro, Italy
- Cristina Cosco, MD, Department of Clinical and Experimental Medicine, Magna Graecia, University of Catanzaro, Catanzaro, Italy
- Elena Tino MD, Department of Clinical and Experimental Medicine, Magna Graecia, University of Catanzaro, Catanzaro, Italy
- Raffaele Pagnotta, RN, Department of Clinical and Experimental Medicine, Magna Graecia, University of Catanzaro, Catanzaro, Italy
- Patrizia Doldo, PhD, MD is Professor, Department of Clinical and Experimental Medicine, Magna Graecia, University of Catanzaro, Catanzaro, Italy
| | - Cristina Cosco
- Silvio Simeone, PhD, RN is Assistant Professor, Department of Clinical and Experimental Medicine, Magna Graecia, University of Catanzaro, Catanzaro, Italy
- Rocco Spagnuolo, PhD, MD is Assistant Professor, Department of Health Sciences, Magna Graecia, University of Catanzaro, Catanzaro, Italy
- Cristina Cosco, MD, Department of Clinical and Experimental Medicine, Magna Graecia, University of Catanzaro, Catanzaro, Italy
- Elena Tino MD, Department of Clinical and Experimental Medicine, Magna Graecia, University of Catanzaro, Catanzaro, Italy
- Raffaele Pagnotta, RN, Department of Clinical and Experimental Medicine, Magna Graecia, University of Catanzaro, Catanzaro, Italy
- Patrizia Doldo, PhD, MD is Professor, Department of Clinical and Experimental Medicine, Magna Graecia, University of Catanzaro, Catanzaro, Italy
| | - Elena Tino
- Silvio Simeone, PhD, RN is Assistant Professor, Department of Clinical and Experimental Medicine, Magna Graecia, University of Catanzaro, Catanzaro, Italy
- Rocco Spagnuolo, PhD, MD is Assistant Professor, Department of Health Sciences, Magna Graecia, University of Catanzaro, Catanzaro, Italy
- Cristina Cosco, MD, Department of Clinical and Experimental Medicine, Magna Graecia, University of Catanzaro, Catanzaro, Italy
- Elena Tino MD, Department of Clinical and Experimental Medicine, Magna Graecia, University of Catanzaro, Catanzaro, Italy
- Raffaele Pagnotta, RN, Department of Clinical and Experimental Medicine, Magna Graecia, University of Catanzaro, Catanzaro, Italy
- Patrizia Doldo, PhD, MD is Professor, Department of Clinical and Experimental Medicine, Magna Graecia, University of Catanzaro, Catanzaro, Italy
| | - Raffaele Pagnotta
- Silvio Simeone, PhD, RN is Assistant Professor, Department of Clinical and Experimental Medicine, Magna Graecia, University of Catanzaro, Catanzaro, Italy
- Rocco Spagnuolo, PhD, MD is Assistant Professor, Department of Health Sciences, Magna Graecia, University of Catanzaro, Catanzaro, Italy
- Cristina Cosco, MD, Department of Clinical and Experimental Medicine, Magna Graecia, University of Catanzaro, Catanzaro, Italy
- Elena Tino MD, Department of Clinical and Experimental Medicine, Magna Graecia, University of Catanzaro, Catanzaro, Italy
- Raffaele Pagnotta, RN, Department of Clinical and Experimental Medicine, Magna Graecia, University of Catanzaro, Catanzaro, Italy
- Patrizia Doldo, PhD, MD is Professor, Department of Clinical and Experimental Medicine, Magna Graecia, University of Catanzaro, Catanzaro, Italy
| | - Patrizia Doldo
- Silvio Simeone, PhD, RN is Assistant Professor, Department of Clinical and Experimental Medicine, Magna Graecia, University of Catanzaro, Catanzaro, Italy
- Rocco Spagnuolo, PhD, MD is Assistant Professor, Department of Health Sciences, Magna Graecia, University of Catanzaro, Catanzaro, Italy
- Cristina Cosco, MD, Department of Clinical and Experimental Medicine, Magna Graecia, University of Catanzaro, Catanzaro, Italy
- Elena Tino MD, Department of Clinical and Experimental Medicine, Magna Graecia, University of Catanzaro, Catanzaro, Italy
- Raffaele Pagnotta, RN, Department of Clinical and Experimental Medicine, Magna Graecia, University of Catanzaro, Catanzaro, Italy
- Patrizia Doldo, PhD, MD is Professor, Department of Clinical and Experimental Medicine, Magna Graecia, University of Catanzaro, Catanzaro, Italy
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9
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Aoyama Y, Hiraoka S, Yasutomi E, Inokuchi T, Tanaka T, Takei K, Igawa S, Takeuchi K, Takahara M, Toyosawa J, Yamasaki Y, Kinugasa H, Kato J, Okada H, Otsuka M. Changes of leucine-rich alpha 2 glycoprotein could be a marker of changes of endoscopic and histologic activity of ulcerative colitis. Sci Rep 2025; 15:5248. [PMID: 39939376 PMCID: PMC11822068 DOI: 10.1038/s41598-025-89615-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2024] [Accepted: 02/06/2025] [Indexed: 02/14/2025] Open
Abstract
Leucine-rich alpha 2 glycoprotein (LRG) is one of the serum biomarkers for disease activity of ulcerative colitis (UC). We focused on the correlation between the changes of LRG and the changes of endoscopic and histologic activity of UC, in comparison to the changes of fecal calprotectin (Fcal), fecal immunochemical test (FIT), and C-reactive protein (CRP). Seventy-nine patients with two or more colonoscopies were enrolled, and 123 paired colonoscopies and 121 paired biopsies were examined. With regard to the change of endoscopic/histologic activity between the preceding and subsequent colonoscopy, there was improvement (n = 29/45), unchanging (n = 63/36), and worsening (n = 31/40). The correlations between the changes of marker levels and endoscopic/histologic activity were Fcal; r = 0.50/0.39 and FIT; r = 0.41/0.40, LRG; r = 0.42/0.40 and CRP; r = 0.22/0.17. Furthermore, when the correlation between the changes of LRG levels and the changes of endoscopic/histological activity was compared with those of other markers, the correlation of LRG tended to be superior to those of CRP (CRP vs. LRG; p = 0.08/0.01). LRG is equivalent to fecal markers and superior to CRP, when inferring changes in disease activity of UC based on changes in its level.
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Affiliation(s)
- Yuki Aoyama
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, 2-5-1 Shikata-cho, Kita-ku, Okayama, 700-8558, Japan
| | - Sakiko Hiraoka
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, 2-5-1 Shikata-cho, Kita-ku, Okayama, 700-8558, Japan.
| | - Eriko Yasutomi
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, 2-5-1 Shikata-cho, Kita-ku, Okayama, 700-8558, Japan
| | - Toshihiro Inokuchi
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, 2-5-1 Shikata-cho, Kita-ku, Okayama, 700-8558, Japan
| | - Takehiro Tanaka
- Department of Pathology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine, Okayama, Japan
| | - Kensuke Takei
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, 2-5-1 Shikata-cho, Kita-ku, Okayama, 700-8558, Japan
| | - Shoko Igawa
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, 2-5-1 Shikata-cho, Kita-ku, Okayama, 700-8558, Japan
| | - Keiko Takeuchi
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, 2-5-1 Shikata-cho, Kita-ku, Okayama, 700-8558, Japan
| | - Masahiro Takahara
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, 2-5-1 Shikata-cho, Kita-ku, Okayama, 700-8558, Japan
| | - Junki Toyosawa
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, 2-5-1 Shikata-cho, Kita-ku, Okayama, 700-8558, Japan
| | - Yasushi Yamasaki
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, 2-5-1 Shikata-cho, Kita-ku, Okayama, 700-8558, Japan
| | - Hideaki Kinugasa
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, 2-5-1 Shikata-cho, Kita-ku, Okayama, 700-8558, Japan
| | - Jun Kato
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba, Japan
| | - Hiroyuki Okada
- Department of Gastroenterology, Japanese Red Cross Society Himeji Hospital, Himeji, Japan
| | - Motoyuki Otsuka
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, 2-5-1 Shikata-cho, Kita-ku, Okayama, 700-8558, Japan
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10
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Wang S, Wang P, Wang D, Shen S, Wang S, Li Y, Chen H. Postbiotics in inflammatory bowel disease: efficacy, mechanism, and therapeutic implications. JOURNAL OF THE SCIENCE OF FOOD AND AGRICULTURE 2025; 105:721-734. [PMID: 39007163 DOI: 10.1002/jsfa.13721] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/27/2024] [Revised: 05/29/2024] [Accepted: 06/19/2024] [Indexed: 07/16/2024]
Abstract
Inflammatory bowel disease (IBD) is one of the most challenging diseases in the 21st century, and more than 10 million people around the world suffer from IBD. Because of the limitations and adverse effects associated with conventional IBD therapies, there has been increased scientific interest in microbial-derived biomolecules, known as postbiotics. Postbiotics are defined as the preparation of inanimate microorganisms and/or their components that confer a health benefit on the host, comprising inactivated microbial cells, cell fractions, metabolites, etc. Postbiotics have shown potential in enhancing IBD treatment by reducing inflammation, modulating the immune system, stabilizing intestinal flora and maintaining the integrity of intestinal barriers. Consequently, they are considered promising adjunctive therapies for IBD. Recent studies indicate that postbiotics offer distinctive advantages, including spanning clinical (safe origin), technological (easy for storage and transportation) and economic (reduced production costs) dimensions, rendering them suitable for widespread applications in functional food/pharmaceutical. This review offers a comprehensive overview of the definition, classification and applications of postbiotics, with an emphasis on their biological activity in both the prevention and treatment of IBD. © 2024 Society of Chemical Industry.
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Affiliation(s)
- Shuxin Wang
- Marine College, Shandong University, Weihai, China
| | - Pu Wang
- Marine College, Shandong University, Weihai, China
| | - Donghui Wang
- Marine College, Shandong University, Weihai, China
| | | | - Shiqi Wang
- Marine College, Shandong University, Weihai, China
| | - Yuanyuan Li
- Department of Food Science, Cornell University, Ithaca, NY, USA
| | - Hao Chen
- Marine College, Shandong University, Weihai, China
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11
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Liu WH, Xiong M, Chen GQ, Long Z, Xu C, Zhu L, Wu JS. Laparoscopic intracorporeal anastomosis vs open anastomosis for ileostomy reversal in Crohn's disease: A single center retrospective study. World J Gastrointest Surg 2025; 17:98269. [PMID: 39872758 PMCID: PMC11757179 DOI: 10.4240/wjgs.v17.i1.98269] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/22/2024] [Revised: 10/24/2024] [Accepted: 11/12/2024] [Indexed: 12/27/2024] Open
Abstract
BACKGROUND There is an increased maturation of laparoscopic intracorporeal anastomosis techniques. However, research on its application for small bowel stoma reversal in patients with Crohn's disease (CD) is limited. Therefore, in this study, we compared the perioperative outcomes between laparoscopic intracorporeal ileostomy reversal (LIIR) and open ileostomy reversal (OIR). AIM To compare the safety, feasibility, bowel function recovery, and short- and long-term LIIR and OIR outcomes in patients with CD. METHODS This study included patients who underwent ileal reversal for CD between January 2021 and January 2023 at our institution. The baseline data, postoperative recovery, and complication indicators were retrospectively analyzed. Logistic regression analysis was conducted to explore factors that significantly influenced the development of enteral nutrition intolerance-related symptoms. RESULTS Notably, 15 of the 45 patients in this study underwent OIR, and the remaining 30 received LIIR. Notably, no statistically significant differences were found between the two groups regarding clinical baseline characteristics, operation time, intraoperative hemorrhage, anastomotic site, enterolysis range, first postoperative flatus, postoperative complications, reoperation rate, or incidence of postoperative enteral nutrition intolerance. Compared with the OIR group, the LIIR group had a shorter postoperative hospital stay (P = 0.045), lower incidence of enteral nutrition intolerance symptoms (P = 0.019), and earlier postoperative total enteral nutrition initiation (P = 0.033); however, it incurred higher total hospital costs (P = 0.038). Furthermore, multivariate logistic regression analysis revealed that the duration of surgery and anastomotic technique were independent risk factors for postoperative symptoms of enteral nutrition intolerance (P < 0.05). CONCLUSION Laparoscopic intracorporeal anastomosis for ileostomy reversal is safe and feasible. Patients who underwent this technique demonstrated improved tolerance to postoperative enteral nutrition and quicker resumption of total enteral nutrition.
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Affiliation(s)
- Wei-Hang Liu
- Department of General Surgery, Chongqing General Hospital, Chongqing 401120, China
| | - Mao Xiong
- Department of General Surgery, Chongqing General Hospital, Chongqing 401120, China
| | - Guo-Qing Chen
- Department of General Surgery, Chongqing General Hospital, Chongqing 401120, China
| | - Zhui Long
- Department of General Surgery, Chongqing General Hospital, Chongqing 401120, China
| | - Chao Xu
- Department of General Surgery, Chongqing General Hospital, Chongqing 401120, China
| | - Li Zhu
- Department of General Surgery, Chongqing General Hospital, Chongqing 401120, China
| | - Jing-Song Wu
- Department of General Surgery, Chongqing General Hospital, Chongqing 401120, China
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12
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Zeng C, Zhu Q, Peng W, Huang C, Chen H, Huang H, Zhou Y, Zhao C. The protective effect of amitriptyline on experimental colitis through inhibiting TLR-4/MD-2 signaling pathway. J Pharmacol Exp Ther 2025; 392:100024. [PMID: 39892990 DOI: 10.1124/jpet.124.002207] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2024] [Revised: 08/23/2024] [Accepted: 08/26/2024] [Indexed: 10/10/2024] Open
Abstract
Amitriptyline, a pleiotropic tricyclic antidepressant, possesses antioxidant and anti-inflammatory properties. Despite its diverse benefits, the specific effects of amitriptyline on inflammatory bowel disease (IBD) are not yet well defined. To explore this, we used a dextran sulfate sodium (DSS)-induced colitis model to examine the anti-inflammatory effects of amitriptyline and the underlying mechanisms by which it operates. Our research revealed that amitriptyline is effective in alleviating several pathological manifestations associated with colitis. This includes improving body weight retention, reducing disease activity index, lessening of colon length shortening, and repairing of colonic mucosal damage. Treatment with amitriptyline significantly protected mucosal injury by preserving the population of goblet cells and increasing the expression of tight junction proteins. Furthermore, we observed that amitriptyline effectively countered immune cell infiltration, specifically neutrophils and macrophages, while simultaneously lowering the levels of inflammatory cytokines such as tumor necrosis factor α, interleukin (IL)-1β, and IL-6. Additionally, RNA sequencing analysis pointed to the potential involvement of the Toll-like receptor (TLR) pathway in the anticolitic effects induced by amitriptyline. Subsequent Western blot analysis indicated that amitriptyline significantly inhibited the TLR-4-mediated nuclear factor (NF)-κB signaling pathway. To bolster our findings, in vitro studies demonstrated that amitriptyline downregulated the TLR-4/NF-κB/mitogen-activated protein kinase signaling cascades in mouse macrophages stimulated with lipopolysaccharide. Further molecular investigations revealed that amitriptyline was able to suppress the elevated expression of myeloid differentiation factor 2 that lipopolysaccharide stimulation typically induces. In summary, our findings suggest that amitriptyline effectively mitigates DSS-induced colitis in mice through the inhibition of TLR-4/myeloid differentiation 2 pathway signaling, indicating its potential repurposing for IBD treatment. SIGNIFICANCE STATEMENT: The potential of using amitriptyline in treating inflammatory bowel disease appears promising, leveraging its established safety and dosing profile as an antidepressant. The study results show that amitriptyline can alleviate pathological symptoms, inflammation, and intestinal mucosal damage in mice with colitis induced by DSS. The protective effect observed appears to be linked to the inhibition of TLR-4/myeloid differentiation 2 signaling pathway. By exploring novel applications for existing medications, we can optimize amitriptyline's efficacy and broaden its impact in both medical and commercial contexts.
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Affiliation(s)
- Chengcheng Zeng
- Department of Gastroenterology, The Second Affiliated Hospital, School of Medical, South China University of Technology, Guangzhou, Guangdong, China; Department of Gastroenterology, Guangzhou Digestive Disease Center, Guangzhou First People's Hospital, Guangzhou, China
| | - Qingqing Zhu
- Department of Gastroenterology, The Second Affiliated Hospital, School of Medical, South China University of Technology, Guangzhou, Guangdong, China; Department of Gastroenterology, Guangzhou Digestive Disease Center, Guangzhou First People's Hospital, Guangzhou, China
| | - Wu Peng
- Department of Gastroenterology, The Second Affiliated Hospital, School of Medical, South China University of Technology, Guangzhou, Guangdong, China; Department of Gastroenterology, Guangzhou Digestive Disease Center, Guangzhou First People's Hospital, Guangzhou, China
| | - Chen Huang
- Department of Gastroenterology, The Second Affiliated Hospital, School of Medical, South China University of Technology, Guangzhou, Guangdong, China; Department of Gastroenterology, Guangzhou Digestive Disease Center, Guangzhou First People's Hospital, Guangzhou, China
| | - Huiting Chen
- Department of Gastroenterology, The Second Affiliated Hospital, School of Medical, South China University of Technology, Guangzhou, Guangdong, China; Department of Gastroenterology, Guangzhou Digestive Disease Center, Guangzhou First People's Hospital, Guangzhou, China
| | - Hongli Huang
- Department of Gastroenterology, The Second Affiliated Hospital, School of Medical, South China University of Technology, Guangzhou, Guangdong, China; Department of Gastroenterology, Guangzhou Digestive Disease Center, Guangzhou First People's Hospital, Guangzhou, China
| | - Yongjian Zhou
- Department of Gastroenterology, The Second Affiliated Hospital, School of Medical, South China University of Technology, Guangzhou, Guangdong, China; Department of Gastroenterology, Guangzhou Digestive Disease Center, Guangzhou First People's Hospital, Guangzhou, China
| | - Chong Zhao
- Department of Gastroenterology, The Second Affiliated Hospital, School of Medical, South China University of Technology, Guangzhou, Guangdong, China; Department of Gastroenterology, Guangzhou Digestive Disease Center, Guangzhou First People's Hospital, Guangzhou, China.
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13
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dos Reis Guerra JA, Magro DO, Rodrigues Coy CS, Valverde DA, de Oliveira ES, Quaresma AB, Kotze PG. Temporal Trends in Surgery and Hospitalization Rates for Crohn's Disease in Brazil: A Population-Based Study. CROHN'S & COLITIS 360 2025; 7:otae082. [PMID: 40207073 PMCID: PMC11979744 DOI: 10.1093/crocol/otae082] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/16/2024] [Indexed: 04/11/2025] Open
Abstract
Introduction Biological therapy has transformed the natural course of inflammatory bowel disease, but there are still controversies regarding its potential to reduce surgical rates for Crohn's disease (CD). This study, conducted with the support of the Brazilian National Healthcare System, aimed to analyze temporal trends in surgery and hospitalization rates among patients with CD and to correlate these data with the dispensing of azathioprine (AZA), infliximab (IFX), and adalimumab (ADA). Methodology This retrospective observational study used data from the National Public Healthcare Department of Informatics through the TT Disease Explorer® platform from 2012 to 2022. Demographic data, medications used, and the prevalence of surgical procedures and hospitalizations associated with the International Classification of Diseases codes for CD were analyzed. Annual average percent changes (AAPCs) were calculated to assess temporal trends. Results Between 2012 and 2022, there was a significant increase of 288.07% in the diagnoses of CD, rising from 27 551 to 106 917 cases. Concurrently, there was an increase in the absolute number of patients treated with AZA, IFX, and ADA, with increasing rates of 65.79%, 251.09%, and 242.48%, respectively. However, the proportion of patients receiving AZA per CD patients decreased by 57.28%, from 44.79% to 19.13% (AAPC = -7.94%, 95% CI, -8.05 to -7.83; P < .001). The use of IFX remained relatively stable, with a slight change from 13.82% to 12.50% (AAPC = 0.01%, 95% CI, -0.20 to 0.22; P = .935), while the use of ADA decreased by 11.75%, from 11.65% to 10.28% (AAPC = -1.74%, 95% CI, -2.48 to -1.82; P < .001). The absolute number of hospitalizations related to CD increased by 57.71%. Despite the rise in the number of cases and the greater availability of biological treatments, the proportion of hospitalized patients decreased by 59.29%, from 6.19% to 2.52% (AAPC = -7.04%, 95% CI, -7.42 to -6.66; P < .001). Similarly, the proportion of surgical procedures relative to the total number of cases decreased by 55.08%, from 1.09% to 0.49% (AAPC = -5.73%, 95% CI, -6.68 to -4.77; P < .001). Conclusions Despite the cumulative increase in the prevalence of CD cases in the country and the absolute increase in the dispensing of biologics, the proportion of hospitalizations and surgical procedures among CD patients treated in the public health system in Brazil decreased.
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Affiliation(s)
| | | | | | | | | | - Abel Botelho Quaresma
- Health Sciences Postgraduate Program, Pontifícia Universidade Católica do Paraná (PUCPR), Curitiba, Brazil
- IBD Outpatient Clinic, Colorectal Surgery Unit, Universidade do Oeste de Santa Catarina, UNOESC, Brazil
| | - Paulo Gustavo Kotze
- Colorectal Surgery Unit, Catholic University of Paraná, IBD Outpatient Clinics, Curitiba, Brazil
- Health Sciences Postgraduate Program, Pontifícia Universidade Católica do Paraná (PUCPR), Curitiba, Brazil
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Mona R, Göldi A, Schneider T, Panne I, Egger A, Niess JH, Hrúz P. Fatigue Is Strongly Associated with Depressive Symptoms in Patients with Inflammatory Bowel Disease. Inflamm Intest Dis 2025; 10:90-103. [PMID: 40337726 PMCID: PMC12058115 DOI: 10.1159/000545572] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/04/2024] [Accepted: 03/21/2025] [Indexed: 05/09/2025] Open
Abstract
Introduction Fatigue is an extraintestinal manifestation in patients with inflammatory bowel disease (IBD), such as Crohn's disease (CD) and ulcerative colitis (UC), with limited information on the underlying factors. This study aimed to determine the prevalence of fatigue and associated factors in IBD patients. Methods This prospective observational study assessed 216 IBD patients treated with intravenous infliximab or vedolizumab. Clinically meaningful fatigue was defined using a visual analog scale with a score ≥4 (VAS-F, range 0-10). Further assessments included the patient health questionnaire (PHQ-8) for depressive symptoms, the IBD-control-8 questionnaire to evaluate subjective disease control and the fatigue impact scale (FIS) for patients' quality of life (QoL). Demographic, clinical and laboratory data of the study population were collected and compared to identify fatigue-associated factors. Results Overall, 53.2% (n = 115) of the IBD patients reported clinically meaningful fatigue with a higher prevalence in UC (63.0%) versus CD (47.4%). Among patients with CD, disease activity was significantly associated with fatigue symptoms (p < 0.001), whereas no such correlation was observed in UC patients (p = 0.85). Clinically meaningful fatigue symptoms were reported in 90.9% of patients with depressive symptoms (PHQ-8 ≥10). Furthermore, patients with fatigue were younger (40 vs. 42 years, p = 0.04), reported more frequent use of concomitant psychoactive and/or sedative medication (p = 0.03) and had lower IBD-control-8 scores (median 12 vs. 16 points, p < 0.001). Only minor differences were observed when comparing serum and fecal laboratory values of patients with fatigue symptoms to those without. Conclusion Fatigue is highly prevalent among IBD patients treated with vedolizumab or infliximab and has a substantial impact on patients' QoL. Fatigue and depressive symptoms were strongly associated, suggesting closer monitoring for depression and the use of psychoactive medication in patients with IBD.
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Affiliation(s)
- Robin Mona
- Department of Gastroenterology and Hepatology, University Digestive Health Care Center, Clarunis, Basel, Switzerland
| | - Andreas Göldi
- Department of Gastroenterology and Hepatology, University Digestive Health Care Center, Clarunis, Basel, Switzerland
| | - Tobias Schneider
- Department of Gastroenterology and Hepatology, University Digestive Health Care Center, Clarunis, Basel, Switzerland
| | - Isabelle Panne
- Department of Gastroenterology and Hepatology, University Digestive Health Care Center, Clarunis, Basel, Switzerland
| | - Andrea Egger
- Division of Endocrinology, Department of Internal Medicine, St. Claraspital, Basel, Switzerland
| | - Jan Hendrik Niess
- Department of Gastroenterology and Hepatology, University Digestive Health Care Center, Clarunis, Basel, Switzerland
- Gastroenterology Group, Department of Biomedicine, University of Basel, Basel, Switzerland
| | - Petr Hrúz
- Department of Gastroenterology and Hepatology, University Digestive Health Care Center, Clarunis, Basel, Switzerland
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15
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Zhang T, Li X, Li J, Sun F, Duan L. Gut microbiome-targeted therapies as adjuvant treatments in inflammatory bowel diseases: a systematic review and network meta-analysis. J Gastroenterol Hepatol 2025; 40:78-88. [PMID: 39482823 DOI: 10.1111/jgh.16795] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/17/2024] [Revised: 09/10/2024] [Accepted: 10/15/2024] [Indexed: 11/03/2024]
Abstract
BACKGROUND AND AIM Gut microbiome-targeted therapies (MTTs), including prebiotics, probiotics, synbiotics, and fecal microbiota transplantation (FMT), have been widely used in inflammatory bowel diseases (IBD), but the best MTTs has not yet been confirmed. We performed a network meta-analysis (NMA) to examine this in ulcerative colitis (UC) and Crohn's disease (CD). METHODS We searched for randomized controlled trials (RCTs) on the efficacy and safety of MTTs as adjuvant therapies for IBD until December 10, 2023. Data were pooled using a random effects model, with efficacy reported as pooled relative risks with 95% CIs, and interventions ranked according to means of surfaces under cumulative ranking values. RESULTS Thirty-eight RCTs met the inclusion criteria. Firstly, we compared the efficacy of MTTs in IBD patients. Only FMT and probiotics were superior to placebo in all outcomes, but FMT ranked best in improving clinical response rate and clinical and endoscopic remission rate, and probiotics ranked second in reducing clinical relapse rate showed significant efficacy, while prebiotics ranked first showed nonsignificant efficacy. Subsequently, we conducted NMA for specific MTT formulations in UC and CD separately, which revealed that FMT, especially combined FMT via colonoscopy and enema, showed significant efficacy and was superior in improving clinical response and remission rate of active UC patients. As for endoscopic remission and clinical relapse, multistrain probiotics based on specific genera of Lactobacillus and Bifidobacterium showed significant efficacy and ranked best in UC. In CD, we found that no MTTs were significantly better than placebo, but synbiotics comprising Bifidobacterium and fructo-oligosaccharide/inulin mix and Saccharomyces ranked best in improving clinical remission and reducing clinical relapse, respectively. Moreover, FMT was safe in both UC and CD. CONCLUSIONS FMT and multistrain probiotics showed superior efficacy in UC. However, the efficacy of MTTs varies among different IBD subtypes and disease stages; thus, the personalized treatment strategies of MTTs are necessary.
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Affiliation(s)
- Tao Zhang
- Department of Gastroenterology, Peking University Third Hospital, Beijing, China
| | - Xiaoang Li
- Department of Gastroenterology, Peking University Third Hospital, Beijing, China
| | - Jun Li
- Department of Gastroenterology, Peking University Third Hospital, Beijing, China
| | - Feng Sun
- China Center for Evidence Based Medical and Clinical Research, Peking University, Beijing, China
- Institute of Public Health, Peking University, Beijing, China
| | - Liping Duan
- Department of Gastroenterology, Peking University Third Hospital, Beijing, China
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16
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Yi L, Han Y, Shen P, Du H, Guo X, Zhou Z, Xiao H. Dietary Porphyra tenera ameliorated dextran sodium sulfate-induced colitis in mice via modulating gut microbiota dysbiosis. Food Chem 2024; 461:140832. [PMID: 39181047 DOI: 10.1016/j.foodchem.2024.140832] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2024] [Revised: 07/31/2024] [Accepted: 08/09/2024] [Indexed: 08/27/2024]
Abstract
Bioactive components from Porphyra tenera (PT) have been reported to confer various health benefits. The role of PT in inflammatory bowel disease (IBD) has not been fully investigated. This study aimed to explore the anti-inflammatory properties of PT on dextran sodium sulfate (DSS)-treated mice. PT supplementation attenuated the severity of colitis in DSS-treated mice, evidenced by the reduction of disease activity index (DAI), restoration of colonic histological damage and suppression of abnormal inflammatory response. Sequencing analysis indicated that intake of PT alleviated DSS-induced gut microbiota dysbiosis, accompanied by reversing the generation of short-chain fatty acids (SCFAs) and bile acids (BAs). Overall, our findings demonstrated that supplementation of PT attenuated the severity of intestinal inflammation and ameliorated gut microbiota dysbiosis in a murine colitis model, which provided a rationale for further application of edible seaweeds for preventing inflammation-related disorders in humans.
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Affiliation(s)
- Lingxiao Yi
- Department of Food Science, University of Massachusetts, Amherst, MA 01003, USA
| | - Yanhui Han
- Department of Food Science, University of Massachusetts, Amherst, MA 01003, USA
| | - Peiyi Shen
- Department of Food Science, University of Massachusetts, Amherst, MA 01003, USA
| | - Hengjun Du
- Department of Food Science, University of Massachusetts, Amherst, MA 01003, USA
| | - Xiaojing Guo
- Department of Food Science, University of Massachusetts, Amherst, MA 01003, USA
| | - Zhihao Zhou
- Department of Food Science, University of Massachusetts, Amherst, MA 01003, USA
| | - Hang Xiao
- Department of Food Science, University of Massachusetts, Amherst, MA 01003, USA.
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17
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Khan ZM, Ball C, Saeed D, Tai G, Chandran S, Vashista A, Davey S, Lee MJ, Brown SR, Hind D, Sayers AE. Appraisal of current surgical guidelines for inflammatory bowel disease using the AGREE-S instrument: A scoping review. Colorectal Dis 2024. [PMID: 39658521 DOI: 10.1111/codi.17258] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/08/2024] [Revised: 10/14/2024] [Accepted: 11/18/2024] [Indexed: 12/12/2024]
Abstract
AIM Guidelines play a crucial role in improving patient care by providing clinicians with up to date evidence-based recommendations. A vast number of guidelines exist on the surgical management of inflammatory bowel disease (IBD). The aim of this scoping review was to identify current surgical IBD guidelines, assess their quality and identify areas of variation between the existing guidelines. METHOD A systematic search of the literature from January 2008 to September 2023 was conducted. After identifying eligible guidelines, they were assessed for quality using the Appraisal of Guidelines for Research and Evaluation for Surgical Interventions (AGREE-S) instrument. Data were extracted on descriptive guideline characteristics and recommendations. RESULTS Fifteen guidelines were identified globally. Most guidelines were published between 2011 and 2023, with six focusing solely on Crohn's disease, five on ulcerative colitis and four on both. Six guidelines focused exclusively on surgical management, while nine contained both medical and surgical recommendations. The overall mean AGREE-S score was 59%, with more recent guidelines scoring higher. CONCLUSIONS The quality of IBD surgical guidelines varies considerably. High-quality, collaborative, international guidelines are needed to reduce duplication and ensure consistent, evidence-based surgical care for IBD patients worldwide. Future guideline development should adhere to the AGREE-S criteria to enhance methodological rigour and transparency.
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Affiliation(s)
- Zarnigar Mussarat Khan
- The Medical School, University of Sheffield, Sheffield, UK
- Academic Directorate of General Surgery, Sheffield Teaching Hospitals, Sheffield, UK
| | - Camille Ball
- The Medical School, University of Sheffield, Sheffield, UK
| | - Dalha Saeed
- The Medical School, University of Sheffield, Sheffield, UK
| | - Grace Tai
- The Medical School, University of Sheffield, Sheffield, UK
| | | | | | - Simon Davey
- Academic Directorate of General Surgery, Sheffield Teaching Hospitals, Sheffield, UK
| | - Matthew James Lee
- Institute of Applied Health Research, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK
| | - Steven R Brown
- The Medical School, University of Sheffield, Sheffield, UK
- Academic Directorate of General Surgery, Sheffield Teaching Hospitals, Sheffield, UK
| | - Daniel Hind
- School of Medicine and Population Health, University of Sheffield, Sheffield, UK
| | - Adele Elizabeth Sayers
- The Medical School, University of Sheffield, Sheffield, UK
- Academic Directorate of General Surgery, Sheffield Teaching Hospitals, Sheffield, UK
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18
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Alipour S, Owrang M, Rajabnia M, Olfatifar M, Kazemian H, Houri H. Prevalence of Plasmid-Mediated Quinolone Resistance Genes in Escherichia coli Isolates From Colonic Biopsies of Iranian Patients With Inflammatory Bowel Diseases: A Cross-Sectional Study. Health Sci Rep 2024; 7:e70204. [PMID: 39698518 PMCID: PMC11652390 DOI: 10.1002/hsr2.70204] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2024] [Revised: 10/29/2024] [Accepted: 11/04/2024] [Indexed: 12/20/2024] Open
Abstract
Background and Aims Emerging evidence suggests that ciprofloxacin and other quinolones can be effectively used as adjuncts to immunosuppressive therapy in managing inflammatory bowel disease (IBD). Clinical isolates of Enterobacterales frequently exhibit quinolone resistance. Additionally, increased IBD severity has been linked to the proliferation of Enterobacterales in the gut. This study aimed to explore the frequency of fluoroquinolone resistance and the presence of associated resistance genes in Escherichia coli isolates obtained from intestinal biopsies of patients with IBD in Iran. Methods In this research, we conducted a study that involved the isolation and examination of E. coli bacteria from inflamed ileal and/or colonic tissues of patients diagnosed with IBD, specifically ulcerative colitis (UC) and Crohn's disease (CD), during colonoscopy procedures. We collected demographic and clinical information from the patients. To identify E. coli strains that were resistant to quinolone antibiotics, we performed both phenotypic and molecular analyses. Results From the colonic and ileal biopsies of 121 patients with IBD, we isolated 107 unique strains of E. coli. Among these strains, 18 (16.8%) were derived from patients with CD, and 89 (83.2%) came from those with UC. Antimicrobial susceptibility tests revealed that 61 out of 107 isolates (57%) of the isolates showed phenotypic resistance to at least one type of quinolone. Additionally, plasmid-mediated quinolone resistance (PMQR) genes, specifically oqxA, oqxB, and qnrS were detected in the E. coli strains linked to both UC and CD. Notably, there was a significant positive correlation observed between intestinal colonization by ciprofloxacin-resistant E. coli and the patients' history of extended ciprofloxacin antibiotic therapy. Conclusion Our results reveal that a significant number of patients with IBD carry quinolone-resistant E. coli. This colonization may pose a risk factor that could affect disease progression and contribute to potential complications.
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Affiliation(s)
- Samira Alipour
- Foodborne and Waterborne Diseases Research Center, Research Institute for Gastroenterology and Liver DiseasesShahid Beheshti University of Medical SciencesTehranIran
| | - Mina Owrang
- Faculty of Medical Science, Sari BranchIslamic Azad UniversitySariIran
| | - Mohsen Rajabnia
- Non‐Communicable Diseases Research CenterAlborz University of Medical SciencesKarajIran
| | - Meysam Olfatifar
- Gastroenterology and Hepatology Diseases Research CenterQom University of Medical SciencesQomIran
| | - Hossein Kazemian
- Clinical Microbiology Research CenterIlam University of Medical SciencesIlamIran
| | - Hamidreza Houri
- Foodborne and Waterborne Diseases Research Center, Research Institute for Gastroenterology and Liver DiseasesShahid Beheshti University of Medical SciencesTehranIran
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19
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Ye YM, Wei MH, Lv KN, Xue XH, Shen R, Liu JH. Effects of an anti-inflammatory diet (AID) on maternal and neonatal health outcomes in pregnant Chinese patients with inflammatory bowel disease treated with infliximab (IFX). Scand J Gastroenterol 2024; 59:1297-1305. [PMID: 39520284 DOI: 10.1080/00365521.2024.2423828] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/28/2024] [Revised: 10/23/2024] [Accepted: 10/27/2024] [Indexed: 11/16/2024]
Abstract
OBJECTIVE This study aimed to evaluate the effects of an anti-inflammatory diet (AID) combined with Infliximab (IFX) therapy on maternal and neonatal health outcomes in pregnant Chinese patients with inflammatory bowel disease (IBD). METHODS IBD patients treated with steady IFX maintenance therapy at the time of conception were randomly assigned to either the IBD-AID group (n = 49), which received an anti-inflammatory diet intervention during the third trimester, or the habitual diet group (n = 49). Primary outcomes included assessments of disease activity, inflammatory markers, and neonatal health. Secondary outcomes included health-related quality of life (HRQoL) in patients and functional gastrointestinal disorders (FGIDs) in infants. RESULTS The IBD-AID intervention significantly reduced disease activity scores in IBD patients at 4 weeks post-intervention and 1 month postpartum compared to the habitual diet group, and also improved HRQoL. Serum C-reactive protein (CRP) and fecal calprotectin (FC) levels were significantly lower in the IBD-AID group at these times, with a trend towards lower levels at 6 months postpartum. Birth weight and Apgar scores were higher in the IBD-AID group but did not reach statistical significance. The incidence of at least one FGID in infants was significantly lower in the IBD-AID group (24.5%) compared to the habitual diet group (46.9%, p = 0.034). CONCLUSION The IBD-AID intervention combined with IFX therapy significantly improved disease activity, inflammatory markers, and QoL in maternal IBD patients, and was associated with a lower incidence of FGIDs in infants, indicating benefits for both maternal and neonatal health.
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Affiliation(s)
- Yong-Mei Ye
- Nursing Department, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Mei-Hao Wei
- Nursing Department, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Kai-Ni Lv
- Nursing Department, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Xiao-Hui Xue
- Nursing Department, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Rui Shen
- Nursing Department, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Jing-Han Liu
- Nursing Department, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China
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20
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Yue Y, Ai J, Chi W, Zhao X, Huo F, Yin C. Biomedical-Optical-Window Tailored Cyanines for Steerable Inflammatory Bowel Disease Theranostic. ADVANCED MATERIALS (DEERFIELD BEACH, FLA.) 2024; 36:e2408450. [PMID: 39240024 DOI: 10.1002/adma.202408450] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/14/2024] [Revised: 08/23/2024] [Indexed: 09/07/2024]
Abstract
Tailored photophysical properties and chemical activity is the ultimate pursuit of functional dyes for in vivo biomedical theranostics. In this work, the independent regulation of the absorption and fluorescence emission wavelengths of heptamethine cyanines is reported. These dyes retain near-infrared fluorescence emission (except a nitro-modified dye) while feature variable absorption wavelengths ranging from 590 to 860 nm. This enables to obtain customized functional dyes that meet the excitation and fluorescence wavelength requirements defined by the optical properties of tissues for in vivo biomedical applications. Typically, a nitro-modified photothermal active derivative Cy-Mu-7-9 is used, which features strong absorption at 810 nm in PBS, a wavelength that balanced the tissue penetration depth and non-specific photothermal effect, to realize non-destructive inflammatory bowel disease (IBD) therapy via photothermal induced up-regulation of heat shock protein 70 in the intestinal epithelial cells. The corresponding amino-modified dye Cy-Mu-7-9-NH2, which can be formed in health enteric cavity by Cy-Mu-7-9 after oral administration, is a fluorescence compound with the emission of 800 nm in PBS. Based on the IBD sensitive transformation of Cy-Mu-7-9 and Cy-Mu-7-9-NH2, in vivo IBD theranostic and therapeutic effect evaluation is realized via the synergy of fluorescence imaging and photothermal therapy for the first time.
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Affiliation(s)
- Yongkang Yue
- Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education, Institute of Molecular Science, Shanxi University, Taiyuan, 030006, P. R. China
| | - Jiahong Ai
- Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education, Institute of Molecular Science, Shanxi University, Taiyuan, 030006, P. R. China
| | - Weijie Chi
- School of Chemistry and Chemical Engineering, Hainan University, Haikou, 570228, China
| | - Xiaoni Zhao
- Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education, Institute of Molecular Science, Shanxi University, Taiyuan, 030006, P. R. China
| | - Fangjun Huo
- Research Institute of Applied Chemistry, Shanxi University, Taiyuan, 030006, P. R. China
| | - Caixia Yin
- Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education, Institute of Molecular Science, Shanxi University, Taiyuan, 030006, P. R. China
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21
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Campos TADM, Anjos LAD, Wady MTB, Wahrlich V. Measured and predicted resting metabolic rate in patients with inflammatory bowel disease. Nutrition 2024; 127:112552. [PMID: 39236524 DOI: 10.1016/j.nut.2024.112552] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2024] [Revised: 07/31/2024] [Accepted: 08/01/2024] [Indexed: 09/07/2024]
Abstract
OBJECTIVE The present study aimed to compare measured and estimated resting metabolic rate (RMR) predicted by selected equations in patients with nonactive inflammatory bowel disease (IBD) on an outpatient university clinic regimen. RESEARCH METHODS & PROCEDURES Seventy-two adult (≥20 years) IBD patients (45 with Crohn's disease-CD) had RMR measured (mRMR) by indirect calorimetry and also estimated by predictive equations (Cunningham, Henry, Anjos et al., and Marra et al.). Body composition was assessed by DXA. Absolute Bias (estimated - mRMR) and % Bias (Bias/mRMR) were calculated. Agreement was assessed as the limit of agreement (LoA) in the Bland & Altman approach. RESULTS There was no difference in age, body composition and mRMR between individuals with CD (5414.2 ± 1023.7 kJ/day) and ulcerative colitis (5443.9 ± 1008.9 kJ/day). Among the equations, only the Anjos et al.'s population-specific equation (-52.1 [642.0] kJ/day, P = 0.493; LoA: -1311; 1206 kJ/d) accurately estimated RMR. The equations of Marra et al. produced the highest % Bias (24.1 ± 14.8%). The Bland & Altman plots showed that the range of the LoA was relatively similar for all equations. In the simple regression analysis, the model with FFM resulted in a higher coefficient of determination (R2 = 0.51 for DC 0.74 for UC) compared to the model that included BM (R2 = 0.35 for DC and 0.65 for UC). CONCLUSIONS Among the equations analyzed, only Anjos et al.'s accurately estimated RMR in outpatients with nonactive IBD. However, caution is advised when applying it at the individual level, due to the wide observed LoA.
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Affiliation(s)
| | - Luiz Antonio Dos Anjos
- Programa de Pós-Graduação em Ciências da Nutrição da Universidade Federal Fluminense, Niterói, Rio de Janeiro, Brazil; Faculdade de Nutrição Emília de Jesus Ferreiro, Universidade Federal Fluminense, Niterói, Rio de Janeiro, Brazil
| | - Maria Thereza Baptista Wady
- Faculdade de Nutrição Emília de Jesus Ferreiro, Universidade Federal Fluminense, Niterói, Rio de Janeiro, Brazil
| | - Vivian Wahrlich
- Programa de Pós-Graduação em Ciências da Nutrição da Universidade Federal Fluminense, Niterói, Rio de Janeiro, Brazil; Faculdade de Nutrição Emília de Jesus Ferreiro, Universidade Federal Fluminense, Niterói, Rio de Janeiro, Brazil
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22
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Feakins RM. Inflammatory disorders of the large intestine. MORSON AND DAWSON'S GASTROINTESTINAL PATHOLOGY 2024:709-857. [DOI: 10.1002/9781119423195.ch35] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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23
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Xie X, Wang Y, Deng B, Blatchley MR, Lan D, Xie Y, Lei M, Liu N, Xu F, Wei Z. Matrix metalloproteinase-responsive hydrogels with tunable retention for on-demand therapy of inflammatory bowel disease. Acta Biomater 2024; 186:354-368. [PMID: 39117116 DOI: 10.1016/j.actbio.2024.07.054] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2024] [Revised: 07/02/2024] [Accepted: 07/29/2024] [Indexed: 08/10/2024]
Abstract
Therapeutic options for addressing inflammatory bowel disease (IBD) include the administration of an enema to reduce intestinal inflammation and alleviate associated symptoms. However, uncontrollable retention of enemas in the intestinal tract has posed a long-term challenge for improving their therapeutic efficacy and safety. Herein we have developed a protease-labile hydrogel system as an on-demand enema vehicle with tunable degradation and drug release rates in response to varying matrix metalloproteinase-9 (MMP-9) expression. The system, composed of three tailored hydrogel networks, is crosslinked by poly (ethylene glycol) (PEG) with 2-, 4- and 8-arms through dynamic hydrazone bonds to confer injectability and generate varying network connectivity. The retention time of the hydrogels can be tuned from 12 to 36 h in the intestine due to their different degradation behaviors induced by MMP-9. The drug-releasing rate of the hydrogels can be controlled from 0.0003 mg/h to 0.278 mg/h. In addition, injection of such hydrogels in vivo resulted in significant differences in therapeutic effects including MMP-9 consumption, colon tissue repair, reduced collagen deposition, and decreased macrophage cells, for treating a mouse model of acute colitis. Among them, GP-8/5-ASA exhibits the best performance. This study validates the effectiveness of the tailored design of hydrogel architecture in response to pathological microenvironment cues, representing a promising strategy for on-demand therapy of IBD. STATEMENT OF SIGNIFICANCE: The uncontrollable retention of enemas at the delivery site poses a long-term challenge for improving therapeutic efficacy in IBD patients. MMP-9 is highly expressed in IBD and correlates with disease severity. Therefore, an MMP-9-responsive GP hydrogel system was developed as an enema by linking multi-armed PEG and gelatin through hydrazone bonds. This forms a dynamic hydrogel characterized by in situ gelation, injectability, enhanced bio-adhesion, biocompatibility, controlled retention time, and regulated drug release. GP hydrogels encapsulating 5-ASA significantly improved the intestinal phenotype of acute IBD and demonstrated notable therapeutic differences with increasing PEG arms. This method represents a promising on-demand IBD therapy strategy and provides insights into treating diseases of varying severities using endogenous stimulus-responsive drug delivery systems.
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Affiliation(s)
- Xueyong Xie
- The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an 710049, PR China; Bioinspired Engineering and Biomechanics Center (BEBC), Xi'an Jiaotong University, Xi'an 710049, PR China
| | - Yaohui Wang
- The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an 710049, PR China; Bioinspired Engineering and Biomechanics Center (BEBC), Xi'an Jiaotong University, Xi'an 710049, PR China
| | - Bo Deng
- The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an 710049, PR China; Bioinspired Engineering and Biomechanics Center (BEBC), Xi'an Jiaotong University, Xi'an 710049, PR China
| | - Michael R Blatchley
- Department of Chemical and Biological Engineering, University of Colorado Boulder 3415 Colorado Ave, Boulder, CO 80303, USA
| | - Dongwei Lan
- The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an 710049, PR China; Bioinspired Engineering and Biomechanics Center (BEBC), Xi'an Jiaotong University, Xi'an 710049, PR China
| | - Yizhou Xie
- The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an 710049, PR China; Bioinspired Engineering and Biomechanics Center (BEBC), Xi'an Jiaotong University, Xi'an 710049, PR China
| | - Meng Lei
- The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an 710049, PR China; Bioinspired Engineering and Biomechanics Center (BEBC), Xi'an Jiaotong University, Xi'an 710049, PR China
| | - Na Liu
- Department of Gastroenterology, Hainan General Hospital (Hainan Affiliated Hospital of Hainan Medical University), Haikou, PR China
| | - Feng Xu
- The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an 710049, PR China; Bioinspired Engineering and Biomechanics Center (BEBC), Xi'an Jiaotong University, Xi'an 710049, PR China
| | - Zhao Wei
- The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an 710049, PR China; Bioinspired Engineering and Biomechanics Center (BEBC), Xi'an Jiaotong University, Xi'an 710049, PR China.
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24
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Zhang JL, Vootukuru N, Niewiadomski O. The effect of solid food diet therapies on the induction and maintenance of remission in Crohn's disease: a systematic review. BMC Gastroenterol 2024; 24:250. [PMID: 39107691 PMCID: PMC11302831 DOI: 10.1186/s12876-024-03315-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/12/2024] [Accepted: 07/03/2024] [Indexed: 08/10/2024] Open
Abstract
BACKGROUND The efficacy of highly restrictive dietary therapies such as exclusive enteral nutrition (EEN) in the induction of remission in Crohn's disease (CD) are well established, however, ongoing issues exist with its poor palatability, restrictions, and adherence. The primary aim of this review is to evaluate the current evidence for the efficacy of exclusively solid food diets on the induction and maintenance of clinical and biochemical remission in CD. Secondary aims include impact on endoscopic healing and quality of life. METHODS A systematic review of all randomised controlled trials (RCTs), open-label randomised trials and head-to-head clinical trials assessing solid food diet intervention in patients with active or inactive Crohn's disease was conducted. Studies included adult and paediatric patients with a verified disease activity index at baseline and follow up (Harvey Bradshaw Index, HBI; Crohn's disease activity index, CDAI and paediatric CDAI, PCDAI). Additional secondary endpoints varied between studies, including endoscopic and biochemical responses, as well as quality of life measures. Two authors independently performed critical appraisals of the studies, including study selection and risk of bias assessments. RESULTS 14 studies were included for review, with several studies suggesting clinically significant findings. Clinical remission was achieved in a paediatric population undertaking the Mediterranean diet (MD) (moderate risk of bias). In adults, the Crohn's disease exclusion diet (CDED) was comparable to the CDED with partial enteral nutrition (PEN) diet in induction of remission (moderate risk of bias). A low fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAP) diet was also shown to decrease symptoms in patients with quiescent or mildly active CD (high risk of bias), however, this was not corroborated by other low FODMAP diet studies. CONCLUSIONS There are promising outcomes for the MD and CDED in inducing clinical remission in mild to moderate CD. The results need to be interpreted with caution due to design limitations, including issues with combining outcomes among CD and UC patients, and small sample size. The current evidence for solid food dietary therapy in CD is limited by the lack of high quality studies and moderate to high bias. Future well designed studies are needed to confirm their efficacy.
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Affiliation(s)
- Jennifer Li Zhang
- Department of Gastroenterology, Eastern Health, Melbourne, VIC, Australia.
| | - Nikil Vootukuru
- Department of Gastroenterology, Eastern Health, Melbourne, VIC, Australia
| | - Olga Niewiadomski
- Department of Gastroenterology, Eastern Health, Melbourne, VIC, Australia
- Monash University, Melbourne, VIC, Australia
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25
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Sturm A, Atreya R, Bettenworth D, Bokemeyer B, Dignass A, Ehehalt R, Germer CT, Grunert PC, Helwig U, Horisberger K, Herrlinger K, Kienle P, Kucharzik T, Langhorst J, Maaser C, Ockenga J, Ott C, Siegmund B, Zeißig S, Stallmach A. Aktualisierte S3-Leitlinie „Diagnostik und Therapie des Morbus Crohn“ der Deutschen Gesellschaft für Gastroenterologie, Verdauungs- und Stoffwechselkrankheiten (DGVS) (Version 4.1) – living guideline. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2024; 62:1229-1318. [PMID: 39111333 DOI: 10.1055/a-2309-6123] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/02/2024]
Affiliation(s)
- Andreas Sturm
- Klinik für Innere Medizin mit Schwerpunkt Gastroenterologie, DRK Kliniken Berlin Westend, Berlin, Deutschland
| | - Raja Atreya
- Medizinische Klinik 1, Universitätsklinikum Erlangen, Erlangen, Deutschland
| | | | - Bernd Bokemeyer
- Gastroenterologische Gemeinschaftspraxis Minden, Minden, Deutschland
| | - Axel Dignass
- Medizinische Klinik I, Agaplesion Markus Krankenhaus, Frankfurt am Main, Deutschland
| | | | | | - P C Grunert
- Klinik für Innere Medizin IV (Gastroenterologie, Hepatologie und Infektiologie), Universitätsklinikum Jena, Deutschland
| | - Ulf Helwig
- Internistische Praxengemeinschaft, Oldenburg, Deutschland
| | - Karoline Horisberger
- Universitätsmedizin Johannes Gutenberg, Universität Klinik f. Allgemein-,Visceral- und Transplantationschirurgie, Mainz, Deutschland
| | | | - Peter Kienle
- Allgemein- und Viszeralchirurgie, Theresienkrankenhaus und Sankt Hedwig-Klinik GmbH, Mannheim, Deutschland
| | - Torsten Kucharzik
- Klinik für Allgemeine Innere Medizin und Gastroenterologie, Klinikum Lüneburg, Lüneburg, Deutschland
| | - Jost Langhorst
- Klinik für Integrative Medizin und Naturheilkunde, Klinikum am Bruderwald, Bamberg, Deutschland
| | - Christian Maaser
- Gastroenterologie, Ambulanzzentrum Lüneburg, Lüneburg, Deutschland
| | - Johann Ockenga
- Medizinische Klinik II, Klinikum Bremen Mitte - Gesundheit Nord, Bremen, Deutschland
| | - Claudia Ott
- Gastroenterologie Facharztzentrum, Regensburg, Deutschland
| | - Britta Siegmund
- Medizinische Klinik I, Charité Universitätsmedizin Berlin, Campus Benjamin Franklin, Deutschland
| | - Sebastian Zeißig
- Medizinische Klinik und Poliklinik I, Universitätsklinikum Dresden, Deutschland
| | - Andreas Stallmach
- Klinik für Innere Medizin IV (Gastroenterologie, Hepatologie und Infektiologie), Universitätsklinikum Jena, Deutschland
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26
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Ke BJ, Abdurahiman S, Biscu F, Zanella G, Dragoni G, Santhosh S, De Simone V, Zouzaf A, van Baarle L, Stakenborg M, Bosáková V, Van Rymenant Y, Verhulst E, Verstockt S, Klein E, Bislenghi G, Wolthuis A, Frič J, Breynaert C, D’Hoore A, Van der Veken P, De Meester I, Lovisa S, Hawinkels LJ, Verstockt B, De Hertogh G, Vermeire S, Matteoli G. Intercellular interaction between FAP+ fibroblasts and CD150+ inflammatory monocytes mediates fibrostenosis in Crohn's disease. J Clin Invest 2024; 134:e173835. [PMID: 39042469 PMCID: PMC11324301 DOI: 10.1172/jci173835] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2023] [Accepted: 06/14/2024] [Indexed: 07/25/2024] Open
Abstract
Crohn's disease (CD) is marked by recurring intestinal inflammation and tissue injury, often resulting in fibrostenosis and bowel obstruction, necessitating surgical intervention with high recurrence rates. To elucidate the mechanisms underlying fibrostenosis in CD, we analyzed the transcriptome of cells isolated from the transmural ileum of patients with CD, including a trio of lesions from each patient: non-affected, inflamed, and stenotic ileum samples, and compared them with samples from patients without CD. Our computational analysis revealed that profibrotic signals from a subset of monocyte-derived cells expressing CD150 induced a disease-specific fibroblast population, resulting in chronic inflammation and tissue fibrosis. The transcription factor TWIST1 was identified as a key modulator of fibroblast activation and extracellular matrix (ECM) deposition. Genetic and pharmacological inhibition of TWIST1 prevents fibroblast activation, reducing ECM production and collagen deposition. Our findings suggest that the myeloid-stromal axis may offer a promising therapeutic target to prevent fibrostenosis in CD.
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Affiliation(s)
- Bo-Jun Ke
- Translational Research Center for Gastrointestinal Disorders (TARGID), Department of Chronic Diseases and Metabolism, KU Leuven, Leuven, Belgium
| | - Saeed Abdurahiman
- Translational Research Center for Gastrointestinal Disorders (TARGID), Department of Chronic Diseases and Metabolism, KU Leuven, Leuven, Belgium
| | - Francesca Biscu
- Translational Research Center for Gastrointestinal Disorders (TARGID), Department of Chronic Diseases and Metabolism, KU Leuven, Leuven, Belgium
- Centre for Inflammation Research, University of Edinburgh, Edinburgh, United Kingdom
| | - Gaia Zanella
- Translational Research Center for Gastrointestinal Disorders (TARGID), Department of Chronic Diseases and Metabolism, KU Leuven, Leuven, Belgium
| | - Gabriele Dragoni
- Translational Research Center for Gastrointestinal Disorders (TARGID), Department of Chronic Diseases and Metabolism, KU Leuven, Leuven, Belgium
- Gastroenterology Research Unit, Department of Experimental and Clinical Biomedical Sciences, University of Florence, Florence, Italy
| | - Sneha Santhosh
- Translational Research Center for Gastrointestinal Disorders (TARGID), Department of Chronic Diseases and Metabolism, KU Leuven, Leuven, Belgium
| | - Veronica De Simone
- Translational Research Center for Gastrointestinal Disorders (TARGID), Department of Chronic Diseases and Metabolism, KU Leuven, Leuven, Belgium
| | - Anissa Zouzaf
- Translational Research Center for Gastrointestinal Disorders (TARGID), Department of Chronic Diseases and Metabolism, KU Leuven, Leuven, Belgium
| | - Lies van Baarle
- Translational Research Center for Gastrointestinal Disorders (TARGID), Department of Chronic Diseases and Metabolism, KU Leuven, Leuven, Belgium
| | - Michelle Stakenborg
- Translational Research Center for Gastrointestinal Disorders (TARGID), Department of Chronic Diseases and Metabolism, KU Leuven, Leuven, Belgium
| | - Veronika Bosáková
- Department of Biology, Faculty of Medicine, Masaryk University, Brno, Czech Republic
- International Clinical Research Center, St. Anne’s University Hospital Brno, Brno, Czech Republic
| | - Yentl Van Rymenant
- Department of Pharmaceutical Sciences, University of Antwerp, Antwerp, Belgium
| | - Emile Verhulst
- Department of Pharmaceutical Sciences, University of Antwerp, Antwerp, Belgium
| | - Sare Verstockt
- Translational Research Center for Gastrointestinal Disorders (TARGID), Department of Chronic Diseases and Metabolism, KU Leuven, Leuven, Belgium
| | - Elliott Klein
- Department of Immunology and Respiratory Research, Boehringer Ingelheim Pharmaceuticals Inc., Ridgefield, Connecticut, USA
| | - Gabriele Bislenghi
- Department of Abdominal Surgery, University Hospitals Leuven, Leuven, Belgium
| | - Albert Wolthuis
- Department of Abdominal Surgery, University Hospitals Leuven, Leuven, Belgium
| | - Jan Frič
- International Clinical Research Center, St. Anne’s University Hospital Brno, Brno, Czech Republic
- International Clinical Research Center, Faculty of Medicine, Masaryk University, Brno, Czech Republic
- Institute of Hematology and Blood Transfusion, Prague, Czech Republic
| | - Christine Breynaert
- Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium
| | - Andre D’Hoore
- Department of Abdominal Surgery, University Hospitals Leuven, Leuven, Belgium
| | | | - Ingrid De Meester
- Department of Pharmaceutical Sciences, University of Antwerp, Antwerp, Belgium
| | - Sara Lovisa
- Department of Biomedical Sciences, Humanitas University, Milan, Italy
| | - Lukas J.A.C. Hawinkels
- Department of Gastroenterology-Hepatology, Leiden University Medical Center, Leiden, Netherlands
| | - Bram Verstockt
- Translational Research Center for Gastrointestinal Disorders (TARGID), Department of Chronic Diseases and Metabolism, KU Leuven, Leuven, Belgium
- Department of Gastroenterology and Hepatology, University Hospitals Leuven, Leuven, Belgium
| | - Gert De Hertogh
- Laboratory of Pathology, University Hospitals Leuven, Leuven, Belgium
- Laboratory of Translational Cell and Tissue Research, Department of Imaging and Pathology, KU Leuven, Leuven, Belgium
| | - Séverine Vermeire
- Translational Research Center for Gastrointestinal Disorders (TARGID), Department of Chronic Diseases and Metabolism, KU Leuven, Leuven, Belgium
- Department of Gastroenterology and Hepatology, University Hospitals Leuven, Leuven, Belgium
| | - Gianluca Matteoli
- Translational Research Center for Gastrointestinal Disorders (TARGID), Department of Chronic Diseases and Metabolism, KU Leuven, Leuven, Belgium
- Leuven Institute for Single Cell Omics (LISCO), KU Leuven, Leuven, Belgium
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Cicerone C, D’Amico F, Allocca M, Zilli A, Parigi TL, Danese S, Furfaro F. A Comprehensive Multidisciplinary Approach to Diagnosing Chronic Inflammatory Bowel Diseases: Integration of Clinical, Endoscopic, and Imaging Modalities. Diagnostics (Basel) 2024; 14:1530. [PMID: 39061667 PMCID: PMC11275644 DOI: 10.3390/diagnostics14141530] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2024] [Revised: 07/12/2024] [Accepted: 07/13/2024] [Indexed: 07/28/2024] Open
Abstract
Chronic inflammatory bowel diseases, such as Crohn's disease and ulcerative colitis, present diagnostic challenges due to their complex and heterogeneous nature. While histology remains fundamental for accurate diagnosis, a multidisciplinary approach incorporating clinical, endoscopic, and imaging modalities is increasingly recognized as essential for comprehensive evaluation. This article delves into the importance of integrating various diagnostic techniques in the assessment of IBD. Colonoscopy and histology, with its ability to directly visualize the intestinal mucosa, play a central role in the diagnostic process. However, histological analysis alone may not suffice, necessitating the inclusion of advanced imaging techniques, such as magnetic resonance enterography (MRE), computed tomography enterography (CTE), and intestinal ultrasound (IUS). These techniques provide valuable insights into the disease's extent, severity, and complications, and should be used in conjunction with biochemical parameters. These modalities complement traditional endoscopic and histological findings, offering a more holistic understanding of the disease process. A multidisciplinary approach that incorporates clinical, endoscopic, histological, serological, and imaging assessments enables clinicians to achieve a more accurate and timely diagnosis of IBD. Moreover, this integrated approach facilitates personalized treatment strategies tailored to individual patient needs, ultimately improving clinical outcomes and quality of life for those affected by chronic inflammatory bowel diseases.
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Affiliation(s)
- Clelia Cicerone
- Department of Gastroenterology and Endoscopy, IRCCS San Raffaele Hospital, 20132 Milan, Italy; (C.C.); (F.D.); (M.A.); (A.Z.); (T.L.P.); (S.D.)
| | - Ferdinando D’Amico
- Department of Gastroenterology and Endoscopy, IRCCS San Raffaele Hospital, 20132 Milan, Italy; (C.C.); (F.D.); (M.A.); (A.Z.); (T.L.P.); (S.D.)
| | - Mariangela Allocca
- Department of Gastroenterology and Endoscopy, IRCCS San Raffaele Hospital, 20132 Milan, Italy; (C.C.); (F.D.); (M.A.); (A.Z.); (T.L.P.); (S.D.)
| | - Alessandra Zilli
- Department of Gastroenterology and Endoscopy, IRCCS San Raffaele Hospital, 20132 Milan, Italy; (C.C.); (F.D.); (M.A.); (A.Z.); (T.L.P.); (S.D.)
| | - Tommaso Lorenzo Parigi
- Department of Gastroenterology and Endoscopy, IRCCS San Raffaele Hospital, 20132 Milan, Italy; (C.C.); (F.D.); (M.A.); (A.Z.); (T.L.P.); (S.D.)
- Department of Gastroenterology and Endoscopy, Vita-Salute San Raffaele University, 20132 Milan, Italy
| | - Silvio Danese
- Department of Gastroenterology and Endoscopy, IRCCS San Raffaele Hospital, 20132 Milan, Italy; (C.C.); (F.D.); (M.A.); (A.Z.); (T.L.P.); (S.D.)
- Department of Gastroenterology and Endoscopy, Vita-Salute San Raffaele University, 20132 Milan, Italy
| | - Federica Furfaro
- Department of Gastroenterology and Endoscopy, IRCCS San Raffaele Hospital, 20132 Milan, Italy; (C.C.); (F.D.); (M.A.); (A.Z.); (T.L.P.); (S.D.)
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28
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Yen HH, Wu JF, Wang HY, Chang TA, Chang CH, Chang CW, Chao TH, Chou JW, Chou YH, Chuang CH, Hsu WH, Hsu TC, Huang TY, Hung TI, Le PH, Lin CC, Lin CC, Lin CP, Lin JK, Lin WC, Ni YH, Shieh MJ, Shih IL, Shun CT, Tsai TJ, Wang CY, Weng MT, Wong JM, Wu DC, Wei SC. Management of ulcerative colitis in Taiwan: consensus guideline of the Taiwan Society of Inflammatory Bowel Disease updated in 2023. Intest Res 2024; 22:213-249. [PMID: 39099217 PMCID: PMC11309818 DOI: 10.5217/ir.2023.00050] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/03/2024] [Revised: 04/25/2024] [Accepted: 04/29/2024] [Indexed: 08/06/2024] Open
Abstract
Ulcerative colitis (UC) is a chronic inflammation of the gastrointestinal tract and is characterized by alternating periods of inflammation and remission. Although UC incidence is lower in Taiwan than in Western countries, its impact remains considerable, demanding updated guidelines for addressing local healthcare challenges and patient needs. The revised guidelines employ international standards and recent research, emphasizing practical implementation within the Taiwanese healthcare system. Since the inception of the guidelines in 2017, the Taiwan Society of Inflammatory Bowel Disease has acknowledged the need for ongoing revisions to incorporate emerging therapeutic options and evolving disease management practices. This updated guideline aims to align UC management with local contexts, ensuring comprehensive and context-specific recommendations, thereby raising the standard of care for UC patients in Taiwan. By adapting and optimizing international protocols for local relevance, these efforts seek to enhance health outcomes for patients with UC.
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Affiliation(s)
- Hsu-Heng Yen
- Department of Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing University, Taichung, Taiwan
- Division of Gastroenterology, Changhua Christian Hospital, Changhua, Taiwan
| | - Jia-Feng Wu
- Department of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan
| | - Horng-Yuan Wang
- Division of Gastroenterology, Department of Internal Medicine, MacKay Memorial Hospital, Taipei, Taiwan
- MacKay Junior College of Medicine, Nursing and Management, Taipei, Taiwan
- MacKay Medical College, Taipei, Taiwan
| | - Ting-An Chang
- Department of Pathology, Taipei City Hospital, Renai-Branch, Taipei, Taiwan
| | - Chung-Hsin Chang
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan
| | - Chen-Wang Chang
- Division of Gastroenterology, Department of Internal Medicine, MacKay Memorial Hospital, Taipei, Taiwan
- MacKay Junior College of Medicine, Nursing and Management, Taipei, Taiwan
- MacKay Medical College, Taipei, Taiwan
| | - Te-Hsin Chao
- Division of Colon and Rectal Surgery, Department of Surgery, Chiayi and Wangiao Branch, Taichung Veterans General Hospital, Taichung, Taiwan
| | - Jen-Wei Chou
- Center for Digestive Medicine, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan
- School of Chinese Medicine, China Medical University, Taichung, Taiwan
| | - Yenn-Hwei Chou
- Division of General Surgery, Department of Surgery, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan
| | - Chiao-Hsiung Chuang
- Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Wen-Hung Hsu
- Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- Department of Internal Medicine, Kaohsiung Municipal Siaogang Hospital, Kaohsiung, Taiwan
| | - Tzu-Chi Hsu
- Division of Colon and Rectal Surgery, Department of Surgery, MacKay Memorial Hospital, MacKay Medical College, Taipei, Taiwan
| | - Tien-Yu Huang
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
| | - Tsung-I Hung
- Division of General Surgery, Department of Surgery, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan
| | - Puo-Hsien Le
- Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Linkou Branch, Taoyuan, Taiwan
- Chang Gung Microbiota Therapy Center, Linkou Chang Gung Memorial Hospital, Linkou Branch, Taoyuan, Taiwan
- Inflammatory Bowel Disease Center, Chang Gung Memorial Hospital, Linkou Branch, Taoyuan, Taiwan
| | - Chun-Che Lin
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Chung Shan Medical University Hospital, Taichung, Taiwan
- Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan
- School of Medicine, Chung Shan Medical University, Taichung, Taiwan
| | - Chun-Chi Lin
- Division of Colon and Rectal Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan
- Department of Surgery, Faculty of Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Ching-Pin Lin
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Chung Shan Medical University Hospital, Taichung, Taiwan
- Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan
- School of Medicine, Chung Shan Medical University, Taichung, Taiwan
| | - Jen-Kou Lin
- Division of Colon and Rectal Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan
- Department of Surgery, Faculty of Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Wei-Chen Lin
- Division of Gastroenterology, Department of Internal Medicine, MacKay Memorial Hospital, Taipei, Taiwan
| | - Yen-Hsuan Ni
- Department of Pediatrics, National Taiwan University College of Medicine and Children’s Hospital, Taipei, Taiwan
| | - Ming-Jium Shieh
- Department of Oncology, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan
| | - I-Lun Shih
- Department of Medical Imaging, National Taiwan University Hospital, Taipei, Taiwan
| | - Chia-Tung Shun
- Department of Forensic Medicine and Pathology, National Taiwan University Hospital, Taipei, Taiwan
- Department of Pathology, Good Liver Clinic, Taipei, Taiwan
| | - Tzung-Jiun Tsai
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
- School of Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Cheng-Yi Wang
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Meng-Tzu Weng
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Department of Medical Research, National Taiwan University Hospital, Hsin-Chu Branch, Hsin-Chu, Taiwan
| | - Jau-Min Wong
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Deng-Chyang Wu
- Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Medical University Gangshan Hospital, Kaohsiung, Taiwan
- Department of Medicine, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- Regenerative Medicine and Cell Therapy Research Center, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Shu-Chen Wei
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
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Melton SL, Day AS, Bryant RV, Halmos EP. Revolution in diet therapy for inflammatory bowel disease. JGH Open 2024; 8:e13097. [PMID: 38957480 PMCID: PMC11217770 DOI: 10.1002/jgh3.13097] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2024] [Revised: 03/24/2024] [Accepted: 05/08/2024] [Indexed: 07/04/2024]
Abstract
Until recently, diet as a therapeutic tool to treat inflammatory bowel disease (IBD) has not been proven effective. Nearly a century in the making we are in the grips of a revolution in diet therapies for IBD, driven by emerging data revealing diet as a key environmental factor associated with IBD susceptibility, and observational studies suggesting that dietary intake may play a role in the disease course of established IBD. This review summarizes the current evidence for diets trialed as induction and maintenance therapy for IBD. For Crohn's disease, exclusive enteral nutrition and the Crohn's disease exclusion diet with partial enteral nutrition are supported by emerging high-quality evidence as induction therapy, but are short-term approaches that are not feasible for prolonged use. Data on diet as maintenance therapy for Crohn's disease are conflicting, with some studies supporting fortification, and others suppression, of certain food components. For ulcerative colitis, data are not as robust for diet as induction and maintenance therapy; however, consistent themes are emerging, suggesting benefits for diets that are plant-based, high in fiber and low in animal protein. Further studies for both Crohn's disease and ulcerative colitis are eagerly awaited, which will allow specific recommendations to be made. Until this time, recommendations default to population based healthy eating guidelines.
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Affiliation(s)
- Sarah L. Melton
- Department of GastroenterologyMonash University & Alfred HealthMelbourneVictoriaAustralia
- Nutrition DepartmentAlfred HealthMelbourneVictoriaAustralia
| | - Alice S. Day
- Inflammatory Bowel Disease Services, Department of Gastroenterology and HepatologyThe Queen Elizabeth HospitalAdelaideSouth AustraliaAustralia
- Faculty of Health Sciences, School of MedicineUniversity of AdelaideAdelaideSouth AustraliaAustralia
- Basil Hetzel Research InstituteWoodville SouthAdelaideSouth AustraliaAustralia
| | - Robert V. Bryant
- Inflammatory Bowel Disease Services, Department of Gastroenterology and HepatologyThe Queen Elizabeth HospitalAdelaideSouth AustraliaAustralia
- Faculty of Health Sciences, School of MedicineUniversity of AdelaideAdelaideSouth AustraliaAustralia
- Basil Hetzel Research InstituteWoodville SouthAdelaideSouth AustraliaAustralia
| | - Emma P. Halmos
- Department of GastroenterologyMonash University & Alfred HealthMelbourneVictoriaAustralia
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30
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Salazar J, Riera P, Gordillo J, Altès A, Martínez M, Serès M, Llaó J, Giordano A, Garcia-Planella E. Predictive role of ITPA genetic variants in thiopurine-related myelotoxicity in Crohn's disease patients. THE PHARMACOGENOMICS JOURNAL 2024; 24:20. [PMID: 38906864 DOI: 10.1038/s41397-024-00341-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/04/2023] [Revised: 06/13/2024] [Accepted: 06/17/2024] [Indexed: 06/23/2024]
Abstract
Thiopurines, an effective therapy for Crohn's disease (CD), often lead to adverse events (AEs). Gene polymorphisms affecting thiopurine metabolism may predict AEs. This retrospective study in CD patients (n = 114) with TPMT activity > 5 Units/Red Blood Cells analyzed TPMT (c.238 G > C, c.460 G > A, c.719 A > G), ITPA (c.94 C > A, IVS2 + 21 A > C), and NUDT15 (c.415 C > T) polymorphisms. All patients received azathioprine (median dose 2.2 mg/kg) with 41.2% experiencing AEs, mainly myelotoxicity (28.1%). No NUDT15 polymorphisms were found, 7% had TPMT, and 31.6% had ITPA polymorphisms. AEs led to therapy modifications in 41.2% of patients. Multivariate analysis identified advanced age (OR 1.046, p = 0.007) and ITPA IVS2 + 21 A > C (OR 3.622, p = 0.015) as independent predictors of AEs. IVS2 + 21 A > C was also associated with myelotoxicity (OR 2.863, p = 0.021). These findings suggest that ITPA IVS2 + 21 A > C polymorphism and advanced age predict AEs during thiopurine therapy for CD with intermediate-normal TPMT activity.
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Affiliation(s)
- Juliana Salazar
- Translational Medical Oncology Laboratory, Institut de Recerca Biomèdica Sant Pau (IIB-Sant Pau), Barcelona, Spain
| | - Pau Riera
- Pharmacy Department, Hospital de la Santa Creu I Sant Pau, Barcelona, Spain
- CIBERER U-705, Barcelona, Spain
| | - Jordi Gordillo
- IBD Unit Gastroenterology Department, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
- Institut de Recerca Biomèdica Sant Pau (IIB-Sant Pau), Barcelona, Spain
| | - Albert Altès
- Hematology Department, Fundació Althaia, Manresa, Barcelona, Spain
| | - Miguel Martínez
- IBD Unit Gastroenterology Department, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
| | - Montserrat Serès
- Emergency Department, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
| | - Jordina Llaó
- IBD Unit Gastroenterology Department, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
| | - Antonio Giordano
- IBD Unit Gastroenterology Department, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
- Institut de Recerca Biomèdica Sant Pau (IIB-Sant Pau), Barcelona, Spain.
| | - Esther Garcia-Planella
- IBD Unit Gastroenterology Department, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
- Institut de Recerca Biomèdica Sant Pau (IIB-Sant Pau), Barcelona, Spain
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31
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Gao H, Peng K, Shi Y, Zhu S, Sun R, Xu C, Liu P, Pang Z, Zhu L, Chen W, Feng B, Wu H, Zhou G, Li M, Li J, Ding B, Liu Z. Development and validation of a novel criterion of histologic healing in ulcerative colitis defined by inflammatory cell enumeration in lamina propria mucosa: A multicenter retrospective cohort in China. Chin Med J (Engl) 2024; 137:1316-1323. [PMID: 38738696 PMCID: PMC11191007 DOI: 10.1097/cm9.0000000000003154] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2023] [Indexed: 05/14/2024] Open
Abstract
BACKGROUND Histological healing is closely associated with improved long-term clinical outcomes and lowered relapses in patients with ulcerative colitis (UC). Here, we developed a novel diagnostic criterion for assessing histological healing in UC patients. METHODS We conducted a retrospective cohort study in UC patients, whose treatment was iteratively optimized to achieve mucosal healing at Shanghai Tenth People's Hospital of Tongji University from January 2017 to May 2022. We identified an inflammatory cell enumeration index (ICEI) for assessing histological healing based on the proportions of eosinophils, CD177 + neutrophils, and CD40L + T cells in the colonic lamina propria under high power field (HPF), and the outcomes (risks of symptomatic relapses) of achieving histological remission vs . persistent histological inflammation using Kaplan-Meier curves. Intrareader reliability and inter-reader reliability were evaluated by each reader. The relationships to the changes in the Nancy index and the Geboes score were also assessed for responsiveness. The ICEI was further validated in a new cohort of UC patients from other nine university hospitals. RESULTS We developed an ICEI for clinical diagnosis of histological healing, i.e., Y = 1.701X 1 + 0.758X 2 + 1.347X 3 - 7.745 (X 1 , X 2 , and X 3 represent the proportions of CD177 + neutrophils, eosinophils, and CD40L + T cells, respectively, in the colonic lamina propria under HPF). The receiver operating characteristics curve (ROC) analysis revealed that Y <-0.391 was the cutoff value for the diagnosis of histological healing and that an area under the curve (AUC) was 0.942 (95% confidence interval [CI]: 0.905-0.979) with a sensitivity of 92.5% and a specificity of 83.6% ( P <0.001). The intraclass correlation coefficient (ICC) for the intrareader reliability was 0.855 (95% CI: 0.781-0.909), and ICEI had good inter-reader reliability of 0.832 (95% CI: 0.748-0.894). During an 18-month follow-up, patients with histological healing had a substantially better outcome compared with those with unachieved histological healing ( P <0.001) using ICEI. During a 12-month follow-up from other nine hospitals, patients with histological healing also had a lower risk of relapse than patients with unachieved histological healing. CONCLUSIONS ICEI can be used to predict histological healing and identify patients with a risk of relapse 12 months and 18 months after clinical therapy. Therefore, ICEI provides a promising, simplified approach to monitor histological healing and to predict the prognosis of UC. REGISTRATION Chinese Clinical Trial Registry, No. ChiCTR2300077792.
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Affiliation(s)
- Han Gao
- Center for IBD Research and Department of Gastroenterology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai 200085, China
| | - Kangsheng Peng
- Center for IBD Research and Department of Gastroenterology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai 200085, China
| | - Yadi Shi
- Clinical Medicine, Sanquan College of Xinxiang Medical University, Xinxiang, Henan 453003, China
| | - Shenshen Zhu
- Center for IBD Research and Department of Gastroenterology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai 200085, China
| | - Ruicong Sun
- Center for IBD Research and Department of Gastroenterology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai 200085, China
| | - Chunjin Xu
- Department of Gastroenterology, The First People’s Hospital of Shangqiu City Affiliated to Xinxiang Medical University, Shangqiu, Henan 476100, China
| | - Ping Liu
- Department of Gastroenterology, Wuhu First People’s Hospital, Wuhu, Anhui 241000, China
| | - Zhi Pang
- Department of Gastroenterology, Suzhou Municipal Hospital Affiliated to Nanjing Medical University, Suzhou, Jiangsu 215008, China
| | - Lanxiang Zhu
- Department of Gastroenterology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 251006, China
| | - Weichang Chen
- Department of Gastroenterology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 251006, China
| | - Baisui Feng
- Department of Gastroenterology, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450014, China
| | - Huili Wu
- Department of Gastroenterology, Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou, Henan 450000, China
| | - Guangxi Zhou
- Department of Gastroenterology, The Affiliated Hospital of Jining Medical College, Jining, Shandong 272004, China
| | - Mingsong Li
- Department of Gastroenterology, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510140, China
| | - Junxiang Li
- Department of Gastroenterology, Dongfang Hospital of Beijing University of Chinese Medicine, Beijing 100078, China
| | - Baijing Ding
- Department of Gastroenterology, Wuhu First People’s Hospital, Wuhu, Anhui 241000, China
| | - Zhanju Liu
- Center for IBD Research and Department of Gastroenterology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai 200085, China
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Aljilani B, Tsintzas K, Siervo M, Moran GW. Association between body mass index and age of disease onset with clinical outcomes in paediatric-onset Crohn's Disease (CD): a UK nation-wide analyses using the NIHR-IBD BioResource. Eur J Clin Nutr 2024; 78:534-540. [PMID: 38472359 PMCID: PMC11182742 DOI: 10.1038/s41430-024-01425-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2023] [Revised: 02/15/2024] [Accepted: 02/27/2024] [Indexed: 03/14/2024]
Abstract
BACKGROUND The evidence on the relationship between adiposity and disease outcomes in paediatric Crohn's disease (CD) is limited and lacks consensus. AIM To investigate the relationship between (a) body mass index (BMI) and clinical CD outcomes (hospitalisation, surgery, disease behaviour, biologic use, extra-intestinal manifestations (EIMs)) and (b) the age of CD onset with clinical outcomes. DESIGN Clinical outcomes were examined in CD patients diagnosed at age <17 years and enroled in the National Institute for Health Research IBD-UK BioResource at a median age of 24 years. All outcomes and BMI were recorded at the time of enrolment. Participants were categorised into normal (<25 kg/m2) and high (≥25 kg/m2) BMI. Age at disease diagnosis was categorised into pre-puberty/early puberty (<11 years), puberty (11-14 years) and post-puberty (15-17 years). Spearman rank correlation was used to test the associations between continuous variables and chi-square test to compare categorical variables. RESULTS 848 participants with CD were included (51.8% males) and median age at diagnosis was 14 years. Participants with high BMI experienced a greater frequency of EIMs (P = 0.05) than those with low BMI (1 type of EIM: 18.5% vs. 13.2%, respectively; ≥2 types of EIMs: 7.8% vs. 5.6%, respectively). Age at diagnosis and BMI showed weak correlations with corticosteroid use (ρ = 0.08, P = 0.03 and ρ = -0.09, P = 0.01; respectively). An early diagnosis (<11 years) was associated with higher occurrence of stenosing and penetrating disease behaviour (P = 0.01) and hospitalisations (P < 0.001). CONCLUSIONS A higher BMI and an earlier age of disease onset are associated with worse CD clinical presentation.
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Affiliation(s)
- Bayan Aljilani
- Department of Clinical Nutrition, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, Saudi Arabia
- Translational Medical Sciences, School of Medicine, The University of Nottingham Medical School, Queen's Medical Centre, Nottingham, UK
| | - Kostas Tsintzas
- School of Life Sciences, The University of Nottingham Medical School, Queen's Medical Centre, Nottingham, UK
| | - Mario Siervo
- School of Life Sciences, The University of Nottingham Medical School, Queen's Medical Centre, Nottingham, UK
| | - Gordon W Moran
- Translational Medical Sciences, School of Medicine, The University of Nottingham Medical School, Queen's Medical Centre, Nottingham, UK.
- National Institute of Health Research Nottingham Biomedical Research Centre, University of Nottingham and Nottingham University Hospitals, Nottingham, UK.
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Li L, Cheng R, Wu Y, Lin H, Gan H, Zhang H. Diagnosis and management of inflammatory bowel disease. J Evid Based Med 2024; 17:409-433. [PMID: 38934234 DOI: 10.1111/jebm.12626] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/01/2024] [Revised: 06/10/2024] [Accepted: 06/13/2024] [Indexed: 06/28/2024]
Abstract
Inflammatory bowel disease (IBD) is a chronic and relapsing immune-mediated disease of the gastrointestinal tract with a gradually increasing global incidence and prevalence. A prolonged course of IBD leads to a decline in patient quality of life and the creation of a substantial economic burden on society. Owing to the lack of specific diagnostic markers, the diagnosis of IBD still needs a gold standard based on a combination of clinical manifestations, imaging, laboratory, and endoscopic results. Accordingly, the current goals of IBD treatment are to alleviate clinical symptoms and reduce recurrence rates. Therefore, it is imperative to develop a standard set of procedures to diagnose and treat IBD. In this review, we summarize prominent and emerging studies, outline classical and contemporary approaches to diagnosing and managing IBD, and integrate multiple guidelines. Furthermore, we propose the possibility of establishing an early and comprehensive diagnostic workflow and personalized management strategy in the future. We aim to enhance the quality and standardization of diagnostic and treatment procedures for IBD.
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Affiliation(s)
- Lili Li
- Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu, China
- Centre for Inflammatory Bowel Disease, West China Hospital, Sichuan University, Chengdu, China
- Lab of Inflammatory Bowel Disease, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, China
| | - Rui Cheng
- Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu, China
- Centre for Inflammatory Bowel Disease, West China Hospital, Sichuan University, Chengdu, China
- Lab of Inflammatory Bowel Disease, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, China
| | - Yushan Wu
- Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu, China
- Centre for Inflammatory Bowel Disease, West China Hospital, Sichuan University, Chengdu, China
- Lab of Inflammatory Bowel Disease, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, China
| | - Hao Lin
- Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu, China
- Centre for Inflammatory Bowel Disease, West China Hospital, Sichuan University, Chengdu, China
- Lab of Inflammatory Bowel Disease, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, China
| | - Huatian Gan
- Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu, China
- Centre for Inflammatory Bowel Disease, West China Hospital, Sichuan University, Chengdu, China
- Lab of Inflammatory Bowel Disease, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, China
- The Center of Gerontology and Geriatrics, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, China
| | - Hu Zhang
- Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu, China
- Centre for Inflammatory Bowel Disease, West China Hospital, Sichuan University, Chengdu, China
- Lab of Inflammatory Bowel Disease, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, China
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Khan IU, Rehman EP, Haq MU, Nayab DE, Shaheen S, Khan S, Hamid M, Godil MS. Causal Effects of Inflammatory Bowel Diseases on the Risk of Kidney Stone Disease. Cureus 2024; 16:e63230. [PMID: 39070306 PMCID: PMC11281688 DOI: 10.7759/cureus.63230] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/25/2024] [Indexed: 07/30/2024] Open
Abstract
BACKGROUND Inflammatory bowel diseases (IBDs), including Crohn's disease and ulcerative colitis, have been increasingly associated with kidney stone disease, posing significant health challenges globally. OBJECTIVE This research sought to determine the causal relationship between kidney stone disease risk and inflammatory bowel disorders. METHODOLOGY This retrospective cohort study included patients with IBDs, such as ulcerative colitis or Crohn's disease, who were diagnosed at least 18 years of age. Information was gathered with an emphasis on patients having comprehensive medical histories and confirmed cases of kidney stone disease from January to December 2022. Medical records were retrospectively evaluated by trained staff to extract treatment information and clinical, radiological, and demographic data. To evaluate relationships, statistical analysis was carried out in SPSS software version 23 using Chi-square tests and descriptive statistics. RESULTS The study included 320 patients diagnosed with IBDs, among which 198 (61.87%) had Crohn's disease, and 122 (38.13%) were diagnosed with ulcerative colitis. The cohort consisted of 140 females (43.75%) and 180 men (56.25%), with a mean age of 45.5 years. Regarding smoking, 113 people (35.31%) reported being smokers, whereas 207 people (64.69%) did not smoke. Additionally, 18 (5.62%) of the population had an underweight BMI, 136 (42.50%) had a normal BMI, 119 (37.19%) had an overweight BMI, and 47 (14.69%) had an obese BMI. Of the patients, 86 (26.88%) had a prior history of kidney stone disease, while 194 (60.62%) did not. Aminosalicylates were the most often used therapy modality for IBD in 189 (58.97%) of cases, followed by corticosteroids in 117 (36.56%) and immunomodulators in 93 (28.94%). Radiological examinations showed that renal calculi were present in 60 (18.75%) of patients, and kidney stones occurred in 40 (12.50%) of patients throughout the research period. The smoking status (p=0.006) and prior history of kidney stones (p<0.001) were the corresponding p-values for the significant results. CONCLUSION The study highlights an increased risk of kidney stone disease in IBD patients, particularly among smokers and those with a recurrent history of kidney stones. Of the 320 patients, 198 (61.87%) had Crohn's disease and 122 (38.13%) had ulcerative colitis, with a significant relationship found between kidney stones and both smoking (113 patients, 35.31%, p=0.006) and a prior history of kidney stones (86 patients, 26.88%, p<0.001). The findings emphasize the need for targeted preventive measures and close monitoring of these high-risk groups.
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Affiliation(s)
| | - Emad Pir Rehman
- General Medicine, Chinar Hospital and Dialysis Center, Abbottabad, PAK
| | - Moeen Ul Haq
- Gastroenterology, Mufti Mahmood Memorial Teaching Hospital and Gomal Medical College, Dera Ismail Khan, PAK
| | - Dur E Nayab
- Gastroenterology, Mufti Mahmood Memorial Teaching Hospital and Gomal Medical College, Dera Ismail Khan, PAK
| | - Seema Shaheen
- General Medicine, Mufti Mahmood Memorial Teaching Hospital, Dera Ismail Khan, PAK
| | - Salman Khan
- Medicine, District Head Quarter Teaching Hospital/Gomal Medical College, Dera Ismail Khan, PAK
| | - Mashhood Hamid
- Family Medicine, King Saud University Medical City, Riyadh, SAU
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Song C, Wu J, Wu J, Wang F. MnO 2 and roflumilast-loaded probiotic membrane vesicles mitigate experimental colitis by synergistically augmenting cAMP in macrophage. J Nanobiotechnology 2024; 22:294. [PMID: 38807127 PMCID: PMC11131305 DOI: 10.1186/s12951-024-02558-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2024] [Accepted: 05/16/2024] [Indexed: 05/30/2024] Open
Abstract
BACKGROUND Ulcerative colitis (UC) is one chronic and relapsing inflammatory bowel disease. Macrophage has been reputed as one trigger for UC. Recently, phosphodiesterase 4 (PDE4) inhibitors, for instance roflumilast, have been regarded as one latent approach to modulating macrophage in UC treatment. Roflumilast can decelerate cyclic adenosine monophosphate (cAMP) degradation, which impedes TNF-α synthesis in macrophage. However, roflumilast is devoid of macrophage-target and consequently causes some unavoidable adverse reactions, which restrict the utilization in UC. RESULTS Membrane vesicles (MVs) from probiotic Escherichia coli Nissle 1917 (EcN 1917) served as a drug delivery platform for targeting macrophage. As model drugs, roflumilast and MnO2 were encapsulated in MVs (Rof&MnO2@MVs). Roflumilast inhibited cAMP degradation via PDE4 deactivation and MnO2 boosted cAMP generation by activating adenylate cyclase (AC). Compared with roflumilast, co-delivery of roflumilast and MnO2 apparently produced more cAMP and less TNF-α in macrophage. Besides, Rof&MnO2@MVs could ameliorate colitis in mouse model and regulate gut microbe such as mitigating pathogenic Escherichia-Shigella and elevating probiotic Akkermansia. CONCLUSIONS A probiotic-based nanoparticle was prepared for precise codelivery of roflumilast and MnO2 into macrophage. This biomimetic nanoparticle could synergistically modulate cAMP in macrophage and ameliorate experimental colitis.
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Affiliation(s)
- Chengjun Song
- State Key Laboratory of Pharmaceutical Biotechnology, Medical School, Nanjing University, Nanjing, 210093, China
| | - Jiamin Wu
- State Key Laboratory of Pharmaceutical Biotechnology, Medical School, Nanjing University, Nanjing, 210093, China
| | - Jinhui Wu
- State Key Laboratory of Pharmaceutical Biotechnology, Medical School, Nanjing University, Nanjing, 210093, China
- Institution of Drug R&D, Nanjing University, Nanjing, 210093, China
- Chemistry and Biomedicine Innovation Center, Nanjing University, Nanjing, 210093, China
| | - Fangyu Wang
- State Key Laboratory of Pharmaceutical Biotechnology, Medical School, Nanjing University, Nanjing, 210093, China.
- Department of Gastroenterology and Hepatology, Nanjing Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, 210002, China.
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Maurud S, Lunde L, Moen A, Opheim R. Exploring the foundations of a digital health information service for patients with inflammatory bowel disease: a mixed method study in Gravitate-Health. BMC Gastroenterol 2024; 24:184. [PMID: 38789953 PMCID: PMC11127442 DOI: 10.1186/s12876-024-03272-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/05/2023] [Accepted: 05/21/2024] [Indexed: 05/26/2024] Open
Abstract
BACKGROUND Providing relevant digital health information of high quality may promote treatment adherence and self-management for patients with inflammatory bowel disease. The development of digital health services is optimised by considering end users' needs. AIM To identify key aspects required for digital promotion of inflammatory bowel disease patients' self-management by exploring their health information needs and the preferences of both patients and healthcare professionals in relation to the digital provision of inflammatory bowel disease health services. METHODS Data from an audit of 1,481 electronic health record summaries from an inflammatory bowel disease help line, 17 semi-structured interviews with inflammatory bowel disease patients and 2 focus group interviews with 11 healthcare professionals were analysed. RESULTS Patients primarily contacted the hospital due to concerns about symptoms, examinations and tests, and medicines. Their concerns appeared to vary according to diagnosis, gender, age and disease duration. The interviews identified two overarching themes: (1) the available health information and patients' health information needs, and (2) whishes, thoughts and preferences for a digital solution in IBD care with relevant and individualised information. CONCLUSIONS The findings delineate key aspects for developing a suitable digital health information service. Patients seek information from healthcare professionals about treatment; however, in a digital solution, they want access to relevant and practical information about the disease, treatment and self-management. Both patients and healthcare professionals saw opportunities for increasing health data availability to patients. However, healthcare professionals expressed concerns about adapting, maintaining and ensuring the relevance of patient health information without increasing their workload and, thus, reducing quality of care.
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Affiliation(s)
- Sigurd Maurud
- Department of Public Health Science, Institute of Health and Society, Faculty of Medicine, University of Oslo, Oslo, Norway.
| | - Lene Lunde
- Department of Public Health Science, Institute of Health and Society, Faculty of Medicine, University of Oslo, Oslo, Norway
| | - Anne Moen
- Department of Public Health Science, Institute of Health and Society, Faculty of Medicine, University of Oslo, Oslo, Norway
| | - Randi Opheim
- Department of Public Health Science, Institute of Health and Society, Faculty of Medicine, University of Oslo, Oslo, Norway
- Department of Gastroenterology, Oslo University Hospital, P.O. Box 1089, Blindern, Oslo, 0318, Norway
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Guo H, Xie W, Ji Z, Wang B, Ren W, Gao W, Yuan B. Oyster Peptides Ameliorate Dextran Sulfate Sodium-Induced Ulcerative Colitis via Modulating the Gut Microbiota and Inhibiting the TLR4/NF-κB Pathway. Nutrients 2024; 16:1591. [PMID: 38892524 PMCID: PMC11175164 DOI: 10.3390/nu16111591] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2024] [Revised: 05/20/2024] [Accepted: 05/21/2024] [Indexed: 06/21/2024] Open
Abstract
Ulcerative colitis (UC) is an inflammatory bowel disease with an increasing prevalence year over year, and the medications used to treat patients with UC clinically have severe side effects. Oyster peptides (OPs) have anti-inflammatory and antioxidant properties as functional foods that can alleviate a wide range of inflammatory conditions. However, the application of oyster peptides in ulcerative colitis is not well studied. In this work, an animal model of acute colitis was established using 3% dextran sulfate sodium (DSS), and the impact of OP therapy on colitis in mice was examined. Supplementing with OPs prevented DSS-induced colitis from worsening, reduced the expression of oxidative stress and inflammatory markers, and restored the intestinal barrier damage caused by DSS-induced colitis in mice. The 16S rDNA results showed that the OP treatment improved the gut microbiota structure of the UC mice, including increasing microbial diversity, increasing beneficial bacteria, and decreasing harmful bacteria. In the UC mice, the OP therapy decreased the relative abundance of Family_XIII_AD3011_group and Prevotella_9 and increased the relative abundance of Alistipes. In conclusion, OP treatment can inhibit the TLR4/NF-κB pathway and improve the intestinal microbiota in UC mice, which in turn alleviates DSS-induced colitis, providing a reference for the treatment of clinical UC patients.
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Affiliation(s)
- Haixiang Guo
- Department of Laboratory Animals, College of Animal Sciences, Jilin University, Changchun 130062, China; (H.G.); (W.X.); (Z.J.); (B.W.); (W.R.)
| | - Wenyin Xie
- Department of Laboratory Animals, College of Animal Sciences, Jilin University, Changchun 130062, China; (H.G.); (W.X.); (Z.J.); (B.W.); (W.R.)
| | - Zhonghao Ji
- Department of Laboratory Animals, College of Animal Sciences, Jilin University, Changchun 130062, China; (H.G.); (W.X.); (Z.J.); (B.W.); (W.R.)
- Department of Basic Medicine, Changzhi Medical College, Changzhi 046000, China
| | - Bingbing Wang
- Department of Laboratory Animals, College of Animal Sciences, Jilin University, Changchun 130062, China; (H.G.); (W.X.); (Z.J.); (B.W.); (W.R.)
| | - Wenzhi Ren
- Department of Laboratory Animals, College of Animal Sciences, Jilin University, Changchun 130062, China; (H.G.); (W.X.); (Z.J.); (B.W.); (W.R.)
| | - Wei Gao
- Department of Laboratory Animals, College of Animal Sciences, Jilin University, Changchun 130062, China; (H.G.); (W.X.); (Z.J.); (B.W.); (W.R.)
| | - Bao Yuan
- Department of Laboratory Animals, College of Animal Sciences, Jilin University, Changchun 130062, China; (H.G.); (W.X.); (Z.J.); (B.W.); (W.R.)
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Yoon J, Hong SW, Han KD, Lee SW, Shin CM, Park YS, Kim N, Lee DH, Kim JS, Yoon H. Risk Factors of Pneumocystis jirovecii Pneumonia in Patients with Inflammatory Bowel Disease: A Nationwide Population-Based Study. Gut Liver 2024; 18:489-497. [PMID: 37867439 PMCID: PMC11096914 DOI: 10.5009/gnl230152] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/24/2023] [Revised: 08/21/2023] [Accepted: 08/22/2023] [Indexed: 10/24/2023] Open
Abstract
Background/Aims : Pneumocystis jirovecii pneumonia (PJP) is a rare but potentially fatal infection. This study was conducted to investigate the risk factors for PJP in inflammatory bowel disease (IBD) patients. Methods : This nationwide, population-based study was conducted in Korea using claims data. Cases of PJP were identified in patients diagnosed with ulcerative colitis (UC) or Crohn's disease (CD) between 2010 and 2017, and the clinical data of each patient was analyzed. Dual and triple therapy was defined as the simultaneous prescription of two or three of the following drugs: steroids, calcineurin inhibitors, immunomodulators, and biologics. Results : During the mean follow-up period (4.6±2.3 years), 84 cases of PJP were identified in 39,462 IBD patients (31 CD and 53 UC). For CD patients, only age at diagnosis >40 years (hazard ratio [HR], 6.12; 95% confidence interval [CI], 1.58 to 23.80) was significantly associated with the risk of PJP, whereas in UC patients, diagnoses of diabetes (HR, 2.51; 95% CI, 1.19 to 5.31) and chronic obstructive pulmonary disease (HR, 3.41; 95% CI, 1.78 to 6.52) showed significant associations with PJP risk. Triple therapy increased PJP risk in both UC (HR, 3.90; 95% CI, 1.54 to 9.88) and CD patients (HR, 5.69; 95% CI, 2.32 to 14.48). However, dual therapy increased PJP risk only in UC patients (HR, 2.53; 95% CI, 1.36 to 4.70). Additionally, 23 patients (27%) received intensive care treatment, and 10 (12%) died within 30 days. Conclusions : PJP risk factors differ in CD and UC patients. Considering the potential fatality of PJP, prophylaxis should be considered for at-risk IBD patients.
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Affiliation(s)
- Jiyoung Yoon
- Department of Internal Medicine, Kangdong Sacred Heart Hospital, Hallym University College of Medicine, Seoul, Korea
| | - Seung Wook Hong
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Kyung-Do Han
- Department of Statistics and Actuarial Science, Soongsil University, Seoul, Korea
| | - Seung-Woo Lee
- Department of Medical Statistics, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Cheol Min Shin
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Young Soo Park
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Nayoung Kim
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Dong Ho Lee
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Joo Sung Kim
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Hyuk Yoon
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
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Nancey S, Hébuterne X, Gilletta C, Hacques E, Roblin X. Prevalence of the Oral Corticosteroid Exposure and Excessive Use in Patients with Inflammatory Bowel Disease: Data from Four French Referral Centers of the International DICE Study. J Clin Med 2024; 13:2652. [PMID: 38731182 PMCID: PMC11084465 DOI: 10.3390/jcm13092652] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2024] [Revised: 04/23/2024] [Accepted: 04/26/2024] [Indexed: 05/13/2024] Open
Abstract
Background: Corticosteroids used to induce a response in Crohn's disease (CD) and ulcerative colitis (UC) may cause adverse reactions. The DICE study aimed to quantify and investigate factors associated with their use. Methods: This cross-sectional, non-interventional study conducted in seven countries allowed us to collect data on oral corticosteroid exposure and excessive use (cf. British Society of Gastroenterology) over the past 12 months in adult patients with CD or UC for more than a year. The factors associated with these practices were investigated using marginal logistic models. We present the results from the four participating French expert centers. Results: Corticosteroid exposure over the past 12 months was observed in 20.1% of 324 CD patients and 30.2% of 205 UC patients. Excessive use was reported in 13.3% and 17.1% of patients, respectively. Corticosteroid exposure and excessive use were less frequently observed in CD than in UC (OR: 0.56, p < 0.0001, and 0.69, p = 0.0042). A disease activity assessment at patient's last visit was the main factor (p < 0.01) associated with the risk of corticosteroid exposure and excessive use in CD (OR: 3.41 and 3.44) and UC (OR: 7.29 and 6.90). Conclusions: Corticosteroid exposure and excessive use continue to be frequently observed in CD and UC in France.
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Affiliation(s)
- Stéphane Nancey
- Hépato-Gastro-Entérologie, CHU de Lyon Sud, 165 Chemin du Grand Revoyet, 69495 Pierre-Bénite, France;
- Faculté de Médecine, Université Claude Bernard Lyon 1, 43 Boulevard du 11 Novembre 1918, 69622 Villeurbanne cedex, France
| | - Xavier Hébuterne
- Gastro-Entérologie et Nutrition Clinique, CHU Hôpital Archet 2, 151 Route St Antoine, 06200 Nice, France;
- Faculté de Médecine, Université Côte d’Azur, Avenue Valrose, 06000 Nice, France
| | - Cyrielle Gilletta
- Gastroentérologie et Pancréatologie, CHU de Toulouse, Hôpital de Rangueil, 1 Avenue Pr Jean Poulhes, 31059 Toulouse, France;
| | - Evguenia Hacques
- Affaires Médicales, AbbVie, 10 rue d’Arcueil, 94528 Rungis cedex, France
| | - Xavier Roblin
- Gastro-Entérologie et Hépatologie Maladies Inflammatoires, CHU de Saint Etienne, Hôpital Bellevue, 25 Boulevard Pasteur, 42100 Saint Etienne, France;
- Faculté de Médecine, Université Jean Monnet, 10 Rue Tréfilerie, 42100 Saint Etienne, France
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Sun Q, Li S, Lin R, Zhao G, Lu J, Liu B, Hu M, Wang W, Yang X, Wei Y, Jia W, Hu Y, Zhang W, Zhu J, Cui D, Zhong L. hUC-MSCs therapy for Crohn's disease: efficacy in TNBS-induced colitis in rats and pilot clinical study. EBioMedicine 2024; 103:105128. [PMID: 38653187 PMCID: PMC11063396 DOI: 10.1016/j.ebiom.2024.105128] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2023] [Revised: 04/03/2024] [Accepted: 04/06/2024] [Indexed: 04/25/2024] Open
Abstract
BACKGROUND The use of mesenchymal stem cells (MSCs) has recently emerged as a promising new therapeutic strategy for many diseases including perianal fistulizing Crohn's disease (CD). Whether hUC-MSCs can promote the healing of luminal ulcer in CD has not been studied so far. METHODS The model of TNBS-induced colitis in rats was used to confirm the efficacy of hUC-MSCs in the treatment of CD. Then, seventeen CD patients refractory to or unsuitable for currently available therapies were enrolled and received once submucosal local injection through colonoscopy combined with once intravenous drip on the next day. All patients received a 24-week follow-up. Clinical and laboratory assessments were monitored at baseline, week 4, 8, 12, and 24. Endoscopic evaluations were conducted at baseline and week 12. Mucosal specimens were obtained at the margin of lesions by endoscopy biopsies and used for RNA sequencing. Two hUC-MSCs co-culture systems were established in vitro, one with the mucosa specimens and the other with M1 macrophages induced from THP1. The expressions of genes representing inflammation (TNFα, IL-6, and IL-1β) and intestinal barrier function (ZO1, CLAUDIN1, and CDH1) were tested by RT-PCR. FINDINGS hUC-MSCs treatment increased body weight and decreased disease activity index (DAI), colon macroscopic damage index (CMDI), and histopathological score (HPS) of rats with TNBS-induced colitis. The results of the clinical study also showed that this mode of hUC-MSCs application was associated with regression of intestinal ulceration. Eight patients (47%) got endoscopic responses (SES-CD improvement of ≥50% from baseline) and three patients (17.65%) got mucosal healing (SES-CD is zero), with a parallel improvement of clinical and laboratory parameters without serious adverse events. RNA sequencing showed hUC-MSCs therapy was associated with an upregulation of transcripts linked to intestinal epithelial barrier integrity and a downregulation of inflammatory signaling pathways in the intestinal mucosa, especially the TNF signaling pathway, IL-17 signaling pathway, and TLR signaling pathway. RNA expression of intestinal epithelial tight junction protein (ZO1, CLAUDIN1, and CDH1), and the RNA expression of major intestinal inflammatory factors in CD (IL-1β, IL-6, and TNFα, p < 0.001 for all) were improved significantly. Moreover, hUC-MSCs could attenuate the polarization of M1 macrophage induced from THP1, thereby decreasing the mRNA expression of IL-1β, IL-6, and TNFα significantly (p < 0.05 for all). TSG-6 expression was evaluated in hUC-MSCs culture supernatant after treatment with TNFα, IFNγ, and LPS for 48 h. And hUC-MSCs could inhibit the phosphorylation of JAK/STAT1 in the intestinal mucosa of CD patients. INTERPRETATION hUC-MSCs transplantation alleviated TNBS-induced colitis in rats. In this pilot clinical study, preliminary data suggested that this approach to administering hUC-MSCs might have potential for clinical efficacy and manageable safety in treating refractory CD, potentially providing hope for better outcomes. No serious adverse events were observed. FUNDING This work was funded by General Program of National Natural Science Foundation of China (Grant No. 82270639), the Scientific research project of Shanghai Municipal Health Committee (Grant No. 202240001), Specialty Feature Construction Project of Shanghai Pudong New Area Health Commission (Grant No. PWZzb2022-05), Shanghai East Hospital Youth Research and Cultivation Foundation program (Grant No. DFPY2022015), Peak Disciplines (Type IV) of Institutions of Higher Learning in Shanghai and Technology Development Project of Pudong Science, Technology and Economic Commission of Shanghai (Grant No. PKJ2021-Y08).
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Affiliation(s)
- Qinjuan Sun
- Department of Gastroenterology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, China
| | - Shan Li
- Department of Gastroenterology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, China
| | - Ritian Lin
- Department of Gastroenterology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, China
| | - Guangxi Zhao
- Department of Gastroenterology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, China
| | - Jinlai Lu
- Department of Gastroenterology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, China
| | - Bin Liu
- Department of Instrument Science and Engineering, School of Electronic Information and Electrical Engineering, Shanghai Jiao Tong University, Shanghai 200240, China; National Engineering Research Center for Nanotechnology, Shanghai 200241, China
| | - Miao Hu
- Department of Gastroenterology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, China
| | - Wei Wang
- Department of Gastroenterology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, China
| | - Xiaoqing Yang
- Department of Gastroenterology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, China
| | - Yushuang Wei
- GMP Laboratory of Translational Medical Center for Stem Cell Therapy & Institute for Regenerative Medicine, National Stem Cell Translational Resource Center, Shanghai East Hospital, School of Life Sciences and Technology, Tongji University, Shanghai 200092, China
| | - Wenwen Jia
- GMP Laboratory of Translational Medical Center for Stem Cell Therapy & Institute for Regenerative Medicine, National Stem Cell Translational Resource Center, Shanghai East Hospital, School of Life Sciences and Technology, Tongji University, Shanghai 200092, China
| | - Yanni Hu
- Department of Gastroenterology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, China
| | - Wei Zhang
- Department of Gastroenterology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, China
| | - Jiawen Zhu
- Department of Gastroenterology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, China
| | - Daxiang Cui
- Department of Instrument Science and Engineering, School of Electronic Information and Electrical Engineering, Shanghai Jiao Tong University, Shanghai 200240, China; National Engineering Research Center for Nanotechnology, Shanghai 200241, China.
| | - Lan Zhong
- Department of Gastroenterology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, China; Shanghai Institute of Stem Cell Research and Clinical Translation, Shanghai 200120, China.
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Alotaibi A, Alhubayshi A, Allehibi A, Almtawa A, Alotaibi N, Alghamdi A, Alrajhi S, Alqutub A, Aleid A, Alamr A, Ibrahim B, Alahmari M, Alhamidi H, Ahmad S, AlBayyat H, Alshaya O, Altannir Y, Alghamdi A. Prevalence of Classical Extraintestinal Manifestations among Inflammatory Bowel Disease Patients in Saudi Arabia: A Single Tertiary Center Experience. SAUDI JOURNAL OF MEDICINE & MEDICAL SCIENCES 2024; 12:169-174. [PMID: 38764558 PMCID: PMC11098265 DOI: 10.4103/sjmms.sjmms_139_23] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 03/27/2023] [Revised: 07/26/2023] [Accepted: 02/07/2024] [Indexed: 05/21/2024]
Abstract
Background Patients with inflammatory bowel disease (IBD) may also experience extraintestinal manifestations (EIMs), which can affect various organ systems, and their occurrence is based on disease activity. Objectives To determine the prevalence of EIMs and their most common types among IBD patients from Saudi Arabia. Materials and Methods This retrospective study included all IBD patients aged 14-80 years who visited the Gastroenterology and Hepatology clinics at King Fahad Medical City, Riyadh, between February 2017 and December 2022. The collected data included demographic characteristics, disease characteristics, EIMs, and treatment. Results The study included 578 IBD patients, of which 65 (11.2%) had at least one EIM, with primary sclerosing cholangitis (46.2%) and sacroiliitis (16.9%) being the most common. Patients with ulcerative colitis were more likely to have EIMs than those with Crohn's disease (15.1% vs. 9%; P = 0.026). Patients with ileocolonic (L3) Crohn's disease reported a higher prevalence of EIMs (7.5%) than those with other disease locations (P = 0.012), while in patients with ulcerative colitis, those with extensive colitis (E3) reported higher prevalence of EIMs (19.2%) (P = 0.001). Patients receiving 6 MP had a significantly high prevalence of EIMs (P = 0.014). Conclusion The prevalence of extraintestinal manifestations among IBD patients in Saudi Arabia is 11.2%. These findings suggest the need for clinicians to screen for EIMs and manage them early. Further research is needed to understand the mechanisms underlying EIMs for the development of more effective treatments.
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Affiliation(s)
| | - Abrar Alhubayshi
- Department of Internal Medicine, King Fahad Medical City, Riyadh, Saudi Arabia
| | - Abed Allehibi
- Department of Gastroenterology and Hepatology, Riyadh, Saudi Arabia
| | - Abdullah Almtawa
- Department of Gastroenterology and Hepatology, Riyadh, Saudi Arabia
| | - Nawaf Alotaibi
- Department of Gastroenterology and Hepatology, Riyadh, Saudi Arabia
| | - Adel Alghamdi
- Department of Gastroenterology and Hepatology, Riyadh, Saudi Arabia
| | - Saad Alrajhi
- Department of Gastroenterology and Hepatology, Riyadh, Saudi Arabia
| | - Adel Alqutub
- Department of Gastroenterology and Hepatology, Riyadh, Saudi Arabia
| | - Ahmad Aleid
- Department of Gastroenterology and Hepatology, Riyadh, Saudi Arabia
| | - Abdulrhman Alamr
- Department of Gastroenterology and Hepatology, Riyadh, Saudi Arabia
| | - Bashaar Ibrahim
- Department of Gastroenterology and Hepatology, Riyadh, Saudi Arabia
| | | | - Hussam Alhamidi
- Department of Gastroenterology and Hepatology, Riyadh, Saudi Arabia
| | - Shameem Ahmad
- Department of Gastroenterology and Hepatology, Riyadh, Saudi Arabia
| | - Hadeel AlBayyat
- Department of Internal Medicine, King Fahad Medical City, Riyadh, Saudi Arabia
| | - Osama Alshaya
- Department of Internal Medicine, King Fahad Medical City, Riyadh, Saudi Arabia
| | | | - Ahmed Alghamdi
- Department of Gastroenterology and Hepatology, Riyadh, Saudi Arabia
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Zhang J, Liu C, An P, Chen M, Wei Y, Li J, Zeng S, Xiang D, Cai Y, Li J, Chen B, Cui L, Qian J, Liu Z, Jiang C, Shi J, Wu K, Dong W, Psychology Club of Inflammatory Bowel Disease Group, Chinese Society of Gastroenterology, Chinese Medical Association; Chinese Association for Mental Hygiene. Psychological symptoms and quality of life in patients with inflammatory bowel disease in China: A multicenter study. United European Gastroenterol J 2024; 12:374-389. [PMID: 38315582 PMCID: PMC11017770 DOI: 10.1002/ueg2.12532] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/26/2023] [Accepted: 11/21/2023] [Indexed: 02/07/2024] Open
Abstract
AIMS To investigate the current situation of mental psychology and quality of life (QoL) in patients with inflammatory bowel disease (IBD) in China, and analyze the influencing factors. METHODS A unified questionnaire was developed to collect clinical data on IBD patients from 42 hospitals in 22 provinces from September 2021 to May 2022. Multivariate Logistic regression analysis was conducted, and independent influencing factors were screened out to construct nomogram. The consistency index (C-index), receiver operating characteristic (ROC) curve, area under the ROC curve (AUC), calibration curve, and decision curve analysis (DCA) were used to evaluate the discrimination, accuracy, and clinical utility of the nomogram model. RESULTS A total of 2478 IBD patients were surveyed, including 1371 patients with ulcerative colitis (UC) and 1107 patients with Crohn's disease (CD). Among them, 25.5%, 29.7%, 60.2%, and 37.7% of IBD patients had anxiety, depression, sleep disturbance and poor QoL, respectively. The proportion of anxiety, depression, and poor QoL in UC patients was significantly higher than that in CD patients (all p < 0.05), but there was no difference in sleep disturbance between them (p = 0.737). Female, higher disease activity and the first visit were independent risk factors for anxiety, depression and sleep disturbance in IBD patients (all p < 0.05). The first visit, higher disease activity, abdominal pain and diarrhea symptoms, anxiety, depression and sleep disturbance were independent risk factors for the poor QoL of patients (all p < 0.05). The AUC value of the nomogram prediction model for predicting poor QoL was 0.773 (95% CI: 0.754-0.792). The calibration diagram of the model showed that the calibration curve fit well with the ideal curve, and DCA showed that the nomogram model could bring clinical benefits. CONCLUSION IBD patients have higher anxiety, depression, and sleep disturbance, which affect their QoL. The nomogram prediction model we constructed has high accuracy and performance when predicting QoL.
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Affiliation(s)
- Jixiang Zhang
- Department of GastroenterologyRenmin Hospital of Wuhan UniversityWuhanChina
| | - Chuan Liu
- Department of GastroenterologyRenmin Hospital of Wuhan UniversityWuhanChina
| | - Ping An
- Department of GastroenterologyRenmin Hospital of Wuhan UniversityWuhanChina
| | - Min Chen
- Department of GastroenterologyXijing HospitalAir Force Medical UniversityXi'anChina
| | - Yuping Wei
- Department of GastroenterologyRenmin Hospital of Wuhan UniversityWuhanChina
| | - Jinting Li
- Department of GastroenterologyRenmin Hospital of Wuhan UniversityWuhanChina
| | - Suqi Zeng
- Department of GastroenterologyRenmin Hospital of Wuhan UniversityWuhanChina
| | - Dan Xiang
- Center for Mental HealthRenmin Hospital of Wuhan UniversityWuhanChina
| | - Yanhui Cai
- Department of PsychiatryXijing HospitalAir Force Medical UniversityXi'anChina
| | - Jun Li
- Department of GastroenterologyPeking University Third HospitalBeijingChina
| | - Baili Chen
- Department of GastroenterologyThe First Affiliated Hospital of Sun Yat‐sen UniversityGuangzhouChina
| | - Liqian Cui
- Department of Clinical PsychologyThe First Affiliated Hospital of Sun Yat‐sen UniversityGuangzhouChina
| | - Jiaming Qian
- Department of GastroenterologyPeking Union Medical College HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina
| | - Zhongchun Liu
- Center for Mental HealthRenmin Hospital of Wuhan UniversityWuhanChina
| | - Changqing Jiang
- Department of Clinical PsychologyBeijing Anding HospitalCapital Medical UniversityBeijingChina
| | - Jie Shi
- Department of Medical PsychologyChinese People's Liberation Army Rocket Army Characteristic Medical CenterBeijingChina
| | - Kaichun Wu
- Department of GastroenterologyXijing HospitalAir Force Medical UniversityXi'anChina
| | - Weiguo Dong
- Department of GastroenterologyRenmin Hospital of Wuhan UniversityWuhanChina
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Sumida K, Shrestha P, Mallisetty Y, Thomas F, Gyamlani G, Streja E, Kalantar-Zadeh K, Kovesdy CP. Anti-Tumor Necrosis Factor Therapy and Risk of Kidney Function Decline and Mortality in Inflammatory Bowel Disease. JAMA Netw Open 2024; 7:e246822. [PMID: 38625700 PMCID: PMC11022116 DOI: 10.1001/jamanetworkopen.2024.6822] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/13/2023] [Accepted: 02/16/2024] [Indexed: 04/17/2024] Open
Abstract
Importance Inflammatory bowel disease (IBD) is associated with adverse clinical outcomes, including chronic kidney disease and mortality, due in part to chronic inflammation. Little is known about the effects of anti-tumor necrosis factor (TNF) therapy on kidney disease progression and mortality among patients with new-onset IBD. Objective To examine the association of incident use of TNF inhibitors with subsequent decline in kidney function and risk of all-cause mortality. Design, Setting, and Participants This retrospective cohort study used data from the US Department of Veterans Affairs health care system. Participants were US veterans with new-onset IBD enrolled from October 1, 2004, through September 30, 2019. Data were analyzed from December 2022 to February 2024. Exposures Incident use of TNF inhibitors. Main Outcomes and Measures The main outcomes were at least 30% decline in estimated glomerular filtration rate (eGFR) and all-cause mortality. Results Among 10 689 patients (mean [SD] age, 67.4 [12.3] years; 9999 [93.5%] male) with incident IBD, 3353 (31.4%) had diabetes, the mean (SD) baseline eGFR was 77.2 (19.2) mL/min/1.73 m2, and 1515 (14.2%) were newly initiated on anti-TNF therapy. During a median (IQR) follow-up of 4.1 (1.9-7.0) years, 3367 patients experienced at least 30% decline in eGFR, and over a median (IQR) follow-up of 5.0 (2.5-8.0) years, 2502 patients died. After multivariable adjustments, incident use (vs nonuse) of TNF inhibitors was significantly associated with higher risk of decline in eGFR (adjusted hazard ratio [HR], 1.34 [95% CI, 1.18-1.52]) but was not associated with risk of all-cause mortality (adjusted HR, 1.02 [95% CI, 0.86-1.21]). Similar results were observed in sensitivity analyses. Conclusions and Relevance In this cohort study of US veterans with incident IBD, incident use (vs nonuse) of TNF inhibitors was independently associated with higher risk of progressive eGFR decline but was not associated with risk of all-cause mortality. Further studies are needed to elucidate potentially distinct pathophysiologic contributions of TNF inhibitor use to kidney and nonkidney outcomes in patients with IBD.
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Affiliation(s)
- Keiichi Sumida
- Division of Nephrology, Department of Medicine, University of Tennessee Health Science Center, Memphis
| | - Prabin Shrestha
- Division of Nephrology, Department of Medicine, University of Tennessee Health Science Center, Memphis
| | - Yamini Mallisetty
- Division of Nephrology, Department of Medicine, University of Tennessee Health Science Center, Memphis
| | - Fridtjof Thomas
- Division of Biostatistics, Department of Preventive Medicine, College of Medicine, University of Tennessee Health Science Center, Memphis
| | - Geeta Gyamlani
- Division of Nephrology, Department of Medicine, University of Tennessee Health Science Center, Memphis
- Nephrology Section, Memphis VA Medical Center, Memphis, Tennessee
| | - Elani Streja
- Division of Nephrology, Hypertension, and Kidney Transplantation, Department of Medicine, University of California Irvine School of Medicine, Orange
- Tibor Rubin Veterans Affairs Medical Center, Long Beach, California
| | - Kamyar Kalantar-Zadeh
- Division of Nephrology, Hypertension, and Kidney Transplantation, Department of Medicine, University of California Irvine School of Medicine, Orange
- Tibor Rubin Veterans Affairs Medical Center, Long Beach, California
| | - Csaba P. Kovesdy
- Division of Nephrology, Department of Medicine, University of Tennessee Health Science Center, Memphis
- Nephrology Section, Memphis VA Medical Center, Memphis, Tennessee
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Alqudah A, Qnais E, Gammoh O, Bseiso Y, Wedyan M, Alqudah M, Hatahet T. Cirsimaritin Alleviates Dextran Sodium Sulfate-Induced Acute Colitis in Experimental Animals: A Therapeutic Approach for Inflammatory Bowel Disease. Prev Nutr Food Sci 2024; 29:31-39. [PMID: 38576881 PMCID: PMC10987388 DOI: 10.3746/pnf.2024.29.1.31] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2024] [Revised: 03/06/2024] [Accepted: 03/07/2024] [Indexed: 04/06/2024] Open
Abstract
Inflammatory bowel disease (IBD) is a chronic disease that affects the entire digestive tract. IBD can be classified as ulcerative colitis or Crohn's disease. The key symptoms of IBD include the emergence of abscesses or pustules, pronounced abdominal discomfort, diarrhea, fistulas, and intestinal narrowing, all of which can greatly affect a patient's daily well-being. Several factors, including bacterial infections, immune response irregularities, and changes in the intestinal milieu, can contribute to the onset of IBD. The aim of this study was investigating the role of cirsimaritin in reducing the severity of colitis in animal model. To induce colitis in laboratory Swiss albino mice, a 4% dextran sulfate sodium (DSS) concoction was provided in their hydration source for a duration of six days. Before the onset of colitis, mice were treated with cirsimaritin (10 mg/kg) once daily to evaluate its potential treatment effects against DSS-induced inflammation. The results showed that 10 mg/kg of cirsimaritin decreased colitis severity (P<0.05). Moreover, cirsimaritin successfully reversed the detrimental effects induced by DSS, including weight reduction, colon truncation, tissue-related damage, increased levels of inflammatory cells in the affected region, and secretion of proinflammatory cytokines. Our findings suggest that cirsimaritin can effectively alleviate acute colitis triggered by DSS.
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Affiliation(s)
- Abdelrahim Alqudah
- Department of Clinical Pharmacy and Pharmacy Practice, Faculty of Pharmaceutical Sciences, The Hashemite University, Zarqa 13133, Jordan
| | - Esam Qnais
- Department of Biology and Biotechnology, Faculty of Science, The Hashemite University, Zarqa 13133, Jordan
| | - Omar Gammoh
- Department of Clinical Pharmacy and Pharmacy Practice, Faculty of Pharmacy, Yarmouk University, Irbid 21163, Jordan
| | - Yousra Bseiso
- Department of Biology and Biotechnology, Faculty of Science, The Hashemite University, Zarqa 13133, Jordan
| | - Mohammed Wedyan
- Department of Biology and Biotechnology, Faculty of Science, The Hashemite University, Zarqa 13133, Jordan
| | - Mohammad Alqudah
- Department of Physiology and Biochemistry, Faculty of Medicine, Jordan University of Science and Technology, Irbid 22110, Jordan
- Physiology Department, School of Medicine and Biomedical Sciences, Arabian Gulf University, Manama 26671, Bahrain
| | - Taher Hatahet
- School of Pharmacy, Queen’s University Belfast, Belfast BT7 1NN, UK
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45
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Yang L, Zhang Y, Yao B, Wu Q, Peng L, Yuan L. Timing of first abdominal operation in Crohn's disease based on a diagnostic model. Sci Rep 2024; 14:6099. [PMID: 38480778 PMCID: PMC10937665 DOI: 10.1038/s41598-024-55221-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2023] [Accepted: 02/21/2024] [Indexed: 03/17/2024] Open
Abstract
This study aims to develop a clinical diagnostic model for assessing the need for initial abdominal surgery in patients diagnosed with Crohn's disease (CD) and create a nomogram to facilitate clinical decision-making. A total of 164 surgical CD patients and 230 control CD patients were included in this retrospective analysis. Least Absolute Shrinkage and Selection Operator (Lasso) regression and binomial logistic regression were employed to select clinical variables. The 394 CD patients were randomly allocated to a training set and a validation set in a 7:3 ratio. The filtered variables were used to establish a diagnostic model and nomogram in the training set, subsequently validated in the testing set. Decision Curve Analysis (DCA) and clinical impact curve were constructed to validate the clinical applicability of the model. Binomial logistic regression analysis identified seven clinical variables with a p-value less than 0.01, including Biomarker (B), Waist-to-Height Ratio (WHtR), Intestinal obstruction, Albumin (ALB), Crohn's Disease Activity Index (CDAI), Myocardial Flow Index (MFI), and C-reactive protein (CRP). These variables were utilized to establish the diagnostic model. Calibration curves showed good alignment, with a C-index of 0.996 in the training set and 0.990 in the testing set. DCA and clinical impact curve demonstrated that the diagnostic model had good clinical efficiency and could provide clinical benefits. A validated diagnostic model for determining the timing of the first abdominal operation in CD patients was established and evaluated, showing high discriminative ability, calibration, and clinical efficiency. It can be utilized by clinicians to assess the optimal timing for transitioning CD patients from medical treatment to surgical intervention, providing valuable references for individualized treatment decisions for CD patients.
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Affiliation(s)
- Lichao Yang
- Department of General Surgery, The Second Xiangya Hospital of Central South University, Changsha, 410011, China
| | - Yawei Zhang
- Department of General Surgery, The Second Xiangya Hospital of Central South University, Changsha, 410011, China
| | - Baojia Yao
- Department of General Surgery, The Second Xiangya Hospital of Central South University, Changsha, 410011, China
| | - Qiang Wu
- Department of General Surgery, The Second Xiangya Hospital of Central South University, Changsha, 410011, China
| | - Liangxin Peng
- Department of General Surgery, The Second Xiangya Hospital of Central South University, Changsha, 410011, China
| | - Lianwen Yuan
- Department of General Surgery, The Second Xiangya Hospital of Central South University, Changsha, 410011, China.
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McDonald C, Kerr H, Gibbons E, Lukose T, Cheriyan D, Harewood G, Patchett S, O’Toole A, Kelly O, Boland K. Higher Ustekinumab Levels in Maintenance Therapy are Associated with Greater Mucosal Healing and Mucosal Response in Crohn's Disease: An Experience of 2 IBD Centers. Inflamm Bowel Dis 2024; 30:423-428. [PMID: 37158577 PMCID: PMC10906356 DOI: 10.1093/ibd/izad073] [Citation(s) in RCA: 9] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/22/2022] [Indexed: 05/10/2023]
Abstract
BACKGROUND Ustekinumab (UST), a human monoclonal antibody that binds the p40 subunit of interleukin 12 (IL-12) and IL-23, is licensed for induction and maintenance therapy of moderate to severe inflammatory bowel disease (IBD). To date, there is limited data published on any potential association between ustekinumab serum trough levels and mucosal healing in order to guide treatment strategies and appropriate dosing. AIM This study aims to identify a relationship between maintenance ustekinumab serum trough levels and mucosal healing and/or response in patients with Crohn's disease in an observational cohort study. METHODS Ustekinumab serum trough levels and antibody titres were analyzed in patients on maintenance drug using an ELISA drug-tolerant assay. Mucosal response (MR) was defined as ≥50% reduction in fecal calprotectin level (FC) and/or ≥50% reduction in the Simple Endoscopic Score for Crohn's Disease (SES-CD score). Mucosal healing (MH) was defined as FC ≤150 µg/mL and/or global SES-CD score ≤5. Median trough levels were analyzed using the Kruskal-Wallis test, and logistic regression was used to determine sensitivity and specificity of levels predicting mucosal response. RESULTS Forty-seven patients on maintenance ustekinumab for Crohn's disease were included in this study. The majority were female (66%), with a median age of 40 years (21-78 years). The majority of patients were biologic-experienced (89.4%, n = 42). Patients with histologically confirmed Crohn's disease represented 100% (n = 47) of the cohort. Over one-third of patients (n = 18, 38.3%) were on higher than standard dosing of 90 mg every 8 weeks. Patients with mucosal healing (n = 30) had significantly higher mean serum ustekinumab levels (5.7 µg/mL, SD 6.4) compared with those with no response (1.1 µg/mL, SD 0.52; n = 7, P < .0001). A serum ustekinumab trough level greater than 2.3 µg/mL was associated with MH, with a sensitivity of 100% and specificity of 90.6% (likelihood ratio 10.7). Similarly, for patients with MR (n = 40), we observed a higher mean serum ustekinumab trough level (5.1 µg/mL, SD 6.1) compared with those with no response (1.1 µg/mL, SD 0.52; n = 7, P < .0001). Furthermore, a serum ustekinumab trough level greater than 2.3 µg/mL was associated with a 10-fold increased likelihood of mucosal response vs mucosal nonresponse (sensitivity 100%, specificity 90.5%, likelihood ratio 10.5). CONCLUSION This study demonstrates that higher ustekinumab serum trough levels are associated with a greater likelihood of achieving mucosal healing and mucosal response in patients with Crohn's disease regardless of prior biologic exposure. Further prospective studies are required to correlate target maintenance trough levels and the optimal time to dose-escalate in order to improve patient outcomes.
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Affiliation(s)
- Ciarán McDonald
- Department of Gastroenterology, Beaumont Hospital, RCSI Hospital Group, Dublin 9, Ireland
| | - Hilary Kerr
- Department of Gastroenterology, James Connolly Hospital, RCSI Hospital Group, Dublin 15, Ireland
| | - Eimear Gibbons
- Department of Gastroenterology, James Connolly Hospital, RCSI Hospital Group, Dublin 15, Ireland
| | - Tincymol Lukose
- Department of Gastroenterology, Beaumont Hospital, RCSI Hospital Group, Dublin 9, Ireland
| | - Danny Cheriyan
- Department of Gastroenterology, Beaumont Hospital, RCSI Hospital Group, Dublin 9, Ireland
| | - Gavin Harewood
- Department of Gastroenterology, Beaumont Hospital, RCSI Hospital Group, Dublin 9, Ireland
| | - Stephen Patchett
- Department of Gastroenterology, Beaumont Hospital, RCSI Hospital Group, Dublin 9, Ireland
| | - Aoibhlinn O’Toole
- Department of Gastroenterology, Beaumont Hospital, RCSI Hospital Group, Dublin 9, Ireland
| | - Orlaith Kelly
- Department of Gastroenterology, James Connolly Hospital, RCSI Hospital Group, Dublin 15, Ireland
| | - Karen Boland
- Department of Gastroenterology, Beaumont Hospital, RCSI Hospital Group, Dublin 9, Ireland
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Singh A, Midha V, Kaur K, Mahajan R, Singh D, Kaur R, Kohli A, Chawla A, Sood K, Bansal N, Sood A. Tofacitinib Versus Oral Prednisolone for Induction of Remission in Moderately Active Ulcerative Colitis [ORCHID]: A Prospective, Open-Label, Randomized, Pilot Study. J Crohns Colitis 2024; 18:300-307. [PMID: 37656880 DOI: 10.1093/ecco-jcc/jjad153] [Citation(s) in RCA: 14] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/13/2023] [Indexed: 09/03/2023]
Abstract
BACKGROUND Oral corticosteroids are first-line agents to induce remission in moderately active ulcerative colitis [UC], but are associated with adverse effects. We compared the efficacy and safety of tofacitinib and prednisolone for induction of remission in moderately active UC. METHODS This was a single-centre, prospective, open-label, randomized, active-controlled pilot study. Eligible patients [aged ≥18 years] had moderately active UC. Participants were randomly assigned to receive either prednisolone [40 mg daily, tapered by 5 mg every week] or tofacitinib [10 mg twice daily] for 8 weeks. The primary endpoint was composite remission [defined as total Mayo clinic score ≤2, with endoscopic sub-score of 0 and faecal calprotectin <100 µg/g] at 8 weeks. RESULTS Seventy-eight patients were randomly assigned to either of the treatment groups. At week 8, the proportion of patients achieving composite remission in the tofacitinib [7/43, 16.28%] and prednisolone groups [3/35, 8.57%] were not significantly different (odds ratio [OR] 2.07, 95% confidence interval [CI] 0.49-8.70; p = 0.31). The time to achieve symptomatic remission [normal stool frequency with absence of rectal bleeding] was similar (10 days, interquartile range [IQR 7-18.75] and 10 days [IQR 5-12.5] for tofacitinib and prednisolone, respectively; p = 0.25) in the two groups. One patient each in the tofacitinib and prednisolone group discontinued treatment due to development of pulmonary tuberculosis and pustular acne, respectively. One patient receiving tofacitinib developed herpes zoster, but did not require cessation of therapy. No serious adverse events or major adverse cardiovascular events were observed. CONCLUSION In patients with moderately active UC, there was no difference in the efficacy and safety of tofacitinib and oral prednisolone for induction of remission at 8 weeks. TRAIL REGISTRATION Clinical Trials Registry of India [CTRI/2021/10/037641].
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Affiliation(s)
- Arshdeep Singh
- Department of Gastroenterology, Dayanand Medical College, Ludhiana, Punjab, 141001, India
| | - Vandana Midha
- Department of Internal Medicine, Dayanand Medical College, Ludhiana, Punjab, 141001, India
| | - Kirandeep Kaur
- Department of Pharmacology, Dayanand Medical College, Ludhiana, Punjab, 141001, India
| | - Ramit Mahajan
- Department of Gastroenterology, Dayanand Medical College, Ludhiana, Punjab, 141001, India
| | - Dharmatma Singh
- Department of Gastroenterology, Dayanand Medical College, Ludhiana, Punjab, 141001, India
| | - Ramandeep Kaur
- Department of Gastroenterology, Dayanand Medical College, Ludhiana, Punjab, 141001, India
| | - Aditya Kohli
- Dayanand Medical College, Ludhiana, Punjab, 141001, India
| | | | - Kriti Sood
- Department of Pediatrics, Government Medical College and Rajindra Hospital, Patiala, 147001, India
| | - Namita Bansal
- Research and Development Centre, Dayanand Medical College, Ludhiana, Punjab, 141001, India
| | - Ajit Sood
- Department of Gastroenterology, Dayanand Medical College, Ludhiana, Punjab, 141001, India
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Wushouer X, Aximujiang K, Kadeer N, Aihemaiti A, Zhong L, Yunusi K. Effect of huankuile on colon injury in rats with ulcerative colitis by reducing TNF-α and MMP9. Eur J Med Res 2024; 29:102. [PMID: 38321559 PMCID: PMC10845565 DOI: 10.1186/s40001-024-01695-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2022] [Accepted: 01/24/2024] [Indexed: 02/08/2024] Open
Abstract
OBJECTIVE To explore the mechanism of huankuile (HKL) in colon injury repair in rats with ulcerative colitis (UC). METHODS Fifty SPF Wistar male rats were divided randomly into a normal group, a negative control group, an HKL intervention group ('HKL group') and a 5-aminosalicylic acid intervention group ('5-ASA group'). After 14 days of intervention with corresponding drugs, pathological scores were obtained using the results of immunohistochemical staining; morphological changes were observed by hematoxylin-eosin staining, and the mRNA expression levels of tumour necrosis factor-α (TNF-α), matrix metalloproteinase 9 (MMP9) and interleukin-13 (IL-13) were detected by real-time quantitative PCR. RESULTS After the successful construction of the rat model, it was compared with the rats in the normal group. In the negative group, it was found that the expression of TNF-α and MMP9 was significantly increased in the colonic mucosal epithelia of the rats, the pathological score was significantly increased (P < 0.05), and the mRNA expression levels of TNF-α, MMP9 and IL-13 were increased (P < 0.05). After treatment with HKL, the colonic morphology of the rats returned to normal, the expression of TNF-α and MMP9 in the colonic mucosal epithelium of the rats returned to normal, the pathological score grade was significantly reduced (P < 0.05), and the mRNA expression levels of TNF-α, MMP9 and IL-13 were reduced; these results were largely consistent with those of the normal group, with no statistically significant difference. CONCLUSION HKL effectively improved the general symptoms and tissue injury in UC rats, and the therapeutic effect was better than that of 5-ASA group. Ulcerative colitis in rats increased the expression of TNF-α, MMP9 and IL-13. HKL repaired UC-induced colonic injury in rats by decreasing the expression of TNF-α, MMP9 and IL-13.
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Affiliation(s)
- Xilinguli Wushouer
- Department of Biology, School of Basic Medical Sciences, Xinjiang Medical University, Urumqi, 830017, China
- Xinjiang key laboratory of Molecular Biology for endemic diseases, Urumqi , 830054, China
| | - Kasimujiang Aximujiang
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Xinjiang Medical University, Urumqi, 830017, China
| | - Nafeisha Kadeer
- Department of Biology, School of Basic Medical Sciences, Xinjiang Medical University, Urumqi, 830017, China
| | - Abulaiti Aihemaiti
- The Functional Center, School of Basic Medical Sciences, Xinjiang Medical University, Urumqi, 830017, China
| | - Li Zhong
- The Functional Center, School of Basic Medical Sciences, Xinjiang Medical University, Urumqi, 830017, China
| | - Kurexi Yunusi
- UygurMedical College, Xinjiang Medical University, Urumqi, 830017, China.
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49
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Chen D, Zhou C, Luo Q, Chen C, Liu G. A Mendelian randomization study on causal effects of inflammatory bowel disease on the risk of erectile dysfunction. Sci Rep 2024; 14:2137. [PMID: 38272986 PMCID: PMC10811225 DOI: 10.1038/s41598-024-52712-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2023] [Accepted: 01/23/2024] [Indexed: 01/27/2024] Open
Abstract
This study aimed to evaluate the causal effects of inflammatory bowel disease (IBD) and erectile dysfunction (ED) using Mendelian randomization (MR). All datasets were obtained from the public genome-wide association study database. In the exposure group, 12,882 IBD patients and 21,770 controls were included. A total of 1154 ED patients and 94,024 controls were included in the outcome group. Two-sample MR was conducted to estimate the causal effect of IBD on ED. Furthermore, Crohn's disease (CD) and ulcerative colitis (UC) were exposure factors in subgroup analyses. Weighted median, MR-egger, Inverse-variant weighted (IVW), weighted mode, and simple mode methods were used in MR analysis. Horizontal pleiotropy test, heterogeneity test, and leave-one-out method were utilized to evaluate the sensitivity and stability of results. After analysis, 62, 52, and 36 single nucleotide polymorphisms (SNPs) that IBD-ED, CD-ED, and UC-ED were included, respectively. The incidence of ED was increased by IBD (IVW: OR = 1.110, 95% CI = 1.017-1.211, P = 0.019; P-heterogeneity > 0.05) and, in addition, ED was affected by CD (IVW: OR = 1.085, 95% CI = 1.015-1.160, P = 0.016; P-heterogeneity > 0.05). However, there was no causal effect of UC on ED (IVW: OR = 1.018, 95% CI = 0.917-1.129, P = 0.743; P-heterogeneity < 0.05). All SNPs showed no significant horizontal pleiotropy (P > 0.05). These results indicate that IBD and CD can cause ED; However, UC did not cause ED. Additional research was required to determine causality and potential mechanisms further.
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Affiliation(s)
- Di Chen
- Department of Urology, The Frist Affiliated Hospital of Guangxi Medical University, Nanning, China
| | - Chao Zhou
- Department of Assisted Reproduction, Nanxishan Hospital of Guangxi Zhuang Autonomous Region, Guilin, China
| | - Quanhai Luo
- Department of Urology, Reproductive Hospital of Guangxi Zhuang Autonomous Region, Nanning, China
| | - Changsheng Chen
- Department of Urology, People's Hospital of Guangxi Zhuang Autonomous Region, Nanning, China
| | - Gang Liu
- Department of Urology, Reproductive Hospital of Guangxi Zhuang Autonomous Region, Nanning, China.
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Arthur P, Kalvala AK, Surapaneni SK, Singh MS. Applications of Cannabinoids in Neuropathic Pain: An Updated Review. Crit Rev Ther Drug Carrier Syst 2024; 41:1-33. [PMID: 37824417 PMCID: PMC11228808 DOI: 10.1615/critrevtherdrugcarriersyst.2022038592] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
Abstract
Neuropathic pain is experienced due to injury to the nerves, underlying disease conditions or toxicity induced by chemotherapeutics. Multiple factors can contribute to neuropathic pain such as central nervous system (CNS)-related autoimmune and metabolic disorders, nerve injury, multiple sclerosis and diabetes. Hence, development of pharmacological interventions to reduce the drawbacks of existing chemotherapeutics and counter neuropathic pain is an urgent unmet clinical need. Cannabinoid treatment has been reported to be beneficial for several disease conditions including neuropathic pain. Cannabinoids act by inhibiting the release of neurotransmitters from presynaptic nerve endings, modulating the excitation of postsynaptic neurons, activating descending inhibitory pain pathways, reducing neural inflammation and oxidative stress and also correcting autophagy defects. This review provides insights on the various preclinical and clinical therapeutic applications of cannabidiol (CBD), cannabigerol (CBG), and cannabinol (CBN) in various diseases and the ongoing clinical trials for the treatment of chronic and acute pain with cannabinoids. Pharmacological and genetic experimental strategies have well demonstrated the potential neuroprotective effects of cannabinoids and also elaborated their mechanism of action for the therapy of neuropathic pain.
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Affiliation(s)
- Peggy Arthur
- College of Pharmacy and Pharmaceutical Sciences, Florida Agricultural and Mechanical University, Tallahassee, FL 32307, USA
| | - Anil Kumar Kalvala
- College of Pharmacy and Pharmaceutical Sciences, Florida Agricultural and Mechanical University, Tallahassee, FL 32307, USA
| | - Sunil Kumar Surapaneni
- College of Pharmacy and Pharmaceutical Sciences, Florida Agricultural and Mechanical University, Tallahassee, FL 32307, USA
| | - Mandip Sachdeva Singh
- College of Pharmacy and Pharmaceutical Sciences, Florida Agricultural and Mechanical University, Tallahassee, FL 32307, USA
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