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Tempia Valenta S, Ventura S, Benuzzi F, Rizzello F, Gionchetti P, De Ronchi D, Atti AR, Agostini A, Filippini N. A Heavy Feeling in the Stomach: Neural Correlates of Anxiety in Crohn's Disease. Neurogastroenterol Motil 2025:e70029. [PMID: 40125714 DOI: 10.1111/nmo.70029] [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: 12/02/2024] [Revised: 03/06/2025] [Accepted: 03/11/2025] [Indexed: 03/25/2025]
Abstract
INTRODUCTION Crohn's disease (CD) is a chronic inflammatory condition associated with psychological stress and anxiety. Functional magnetic resonance imaging (fMRI) studies have shown differences in brain function between patients with CD and healthy controls (HC). This study aimed to compare the neural correlates of anxiety inindividuals with CD relative to HC, using resting-state fMRI data. METHODS Participants filled in the State-Trait Anxiety Inventory (STAI), a validated tool for measuring anxiety, and underwent an MRI acquisition, including both structural and functional sequences, to identify brain regions associated with anxiety scores. RESULTS Seventeen patients with CD and eighteen HC matched for age, education, and sex participated in the study. No significant group differences emerged in the STAI scores. However, resting-state fMRI analysis revealed distinct patterns of functional connectivity associated with anxiety scores for the two study groups. Among CD group, greater STAI scores correlated with increased functional connectivity, whereas, in HC, they correlated with decreased functional connectivity. Significant clusters were found in brain regions belonging to specific resting-state networks (RSNs): (a) Posterior Cingulate Cortex (PCC, within the Default Mode Network), (b) left Middle Frontal Gyrus (within the Left Fronto-Parietal Network), and (c) PCC and right Superior Temporal Gyrus (within the Dorsal Attention Network). CONCLUSION The differential association between functional connectivity and STAI scores observed for CD and HC participants was located in areas within self-referential (Default Mode Network) and cognitive (Left Fronto-Parietal Network and Dorsal Attention Network) RSNs. Our findings suggest that maladaptive/dysfunctional processing of negative emotions and visceral sensitivity may occur in patients with CD.
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Affiliation(s)
- Silvia Tempia Valenta
- Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy
- Doctoral Program of Global Health, Humanitarian Aid and Disaster Medicine, Vrije Universiteit Brussel, Bruxelles, Belgium
| | - Sara Ventura
- Department of Clinical and Surgical Sciences, IRCCS Sant'Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy
| | - Francesca Benuzzi
- Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Modena, Italy
| | - Fernando Rizzello
- Department of Clinical and Surgical Sciences, IRCCS Sant'Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy
| | - Paolo Gionchetti
- Department of Clinical and Surgical Sciences, IRCCS Sant'Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy
| | - Diana De Ronchi
- Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy
| | - Anna Rita Atti
- Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy
| | - Alessandro Agostini
- Department of Clinical and Surgical Sciences, IRCCS Sant'Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy
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Wang FT, Lin Y, Gao RY, Wu XC, Wu TQ, Jiao YR, Li JY, Yin L, Chen CQ. Machine learning for temporary stoma after intestinal resection in surgical decision-making of Crohn's disease. BMC Gastroenterol 2025; 25:117. [PMID: 40000985 PMCID: PMC11863836 DOI: 10.1186/s12876-025-03668-7] [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: 10/07/2023] [Accepted: 02/05/2025] [Indexed: 02/27/2025] Open
Abstract
BACKGROUND Crohn's disease (CD) often necessitates surgical intervention, with temporary stoma creation after intestinal resection (IR) being a crucial decision. This study aimed to construct novel models based on machine learning (ML) to predict temporary stoma formation after IR for CD. METHODS Patient data who underwent IR for CD at our center between July 2017 and March 2023 were collected for inclusion in this retrospective study. Eligible CD patients were randomly divided into training and validation cohorts. Feature selection was executed using the least absolute shrinkage and selection operator. We employed three ML algorithms including traditional logistic regression, novel random forest and XG-Boost to create prediction models. The area under the curve (AUC), accuracy, sensitivity, specificity, precision, recall, and F1 score were used to evaluate these models. SHapley Additive exPlanation (SHAP) approach was used to assess feature importance. RESULTS A total of 252 patients with CD were included in the study, 150 of whom underwent temporary stoma creation after IR. Eight independent predictors emerged as the most valuable features. An AUC between 0.886 and 0.998 was noted among the three ML algorithms. The random forest (RF) algorithms demonstrated the most optimal performance (0.998 in the training cohort and 0.780 in the validation cohort). By employing the SHAP method, we identified the variables that contributed to the model and their correlation with temporary stoma formation after IR for CD. CONCLUSIONS The proposed RF model showed a good predictive ability for identifying patients at high risk for temporary stoma formation after IR for CD, which can assist in surgical decision-making in CD management, provide personalized guidance for temporary stoma formation, and improve patient outcomes.
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Affiliation(s)
- Fang-Tao Wang
- Department of Abdominal Surgery, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, 200072, China
| | - Yin Lin
- Department of General Surgery, Yangpu Hospital, Tongji University School of Medicine, Shanghai, 200090, China
| | - Ren-Yuan Gao
- Department of Abdominal Surgery, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, 200072, China
| | - Xiao-Cai Wu
- Department of Abdominal Surgery, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, 200072, China
| | - Tian-Qi Wu
- Department of Abdominal Surgery, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, 200072, China
| | - Yi-Ran Jiao
- Department of Abdominal Surgery, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, 200072, China
| | - Ji-Yuan Li
- Department of Abdominal Surgery, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, 200072, China
| | - Lu Yin
- Department of Abdominal Surgery, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, 200072, China
| | - Chun-Qiu Chen
- Department of Abdominal Surgery, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, 200072, China.
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Albshesh A, Abend A, Yehuda RM, Mahajna H, Ungar B, Ben-Horin S, Kopylov U, Carter D. Intestinal ultrasound accurately predicts future therapy failure in Crohn's disease patients in a biologics-induced remission. Eur J Gastroenterol Hepatol 2025; 37:184-189. [PMID: 39514257 DOI: 10.1097/meg.0000000000002883] [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] [Indexed: 11/16/2024]
Abstract
BACKGROUND Intestinal ultrasound (IUS) is used to assess disease activity, complications, and treatment follow-up in Crohn's disease (CD). Less is known about the association of disease activity on IUS with the risk of future disease relapse during biologically sustained clinical remission in CD. AIM The study aimed to investigate the association between IUS activity parameters and subsequent therapy failure in asymptomatic biologically treated patients with CD. METHODS A retrospective cohort study examined the association between IUS parameters and forthcoming therapy failure (drug discontinuation, dose escalation, corticosteroid use, hospitalization, or surgery) in CD patients on biological therapy in remission. RESULTS A total of 57 patients with ileal (65%) or ileocolonic (35%) CD on biological therapy were included in the study. Therapy failure occurred in 50.8% [defined as need for dose escalation (31%), drug discontinuation (51.7%), steroid use (10.5%), and hospitalization (6.8%)] during a median follow-up of 5 (SD + 9.5) months after IUS. On univariate analysis, a bowel wall thickness (BWT) of 2.5 vs. 4 mm ( P = 0.005), the existence of an enlarged lymph node ( P = 0.02), and the loss of bowel wall stratification ( P = 0.01) were correlated with therapy failure. On multivariable analysis, only BWT ≥ 4 mm was associated with the risk of future treatment failure (hazard ratio, 3.7; 95% confidence interval, 0.6-15; P = 0.02). CONCLUSION Our findings suggest that BWT ≥4 mm during clinical remission is associated with subsequent treatment failure in patients with CD treated with biologics. Our results support the use of IUS for monitoring CD during remission and may point to a novel threshold for predicting disease reactivation.
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Affiliation(s)
- Ahmad Albshesh
- Department of Gastroenterology, Sheba Medical Center Israel, Tel Hashomer
- Faculty of Medical and Health Sciences, Tel-Aviv University, Tel-Aviv
| | - Alon Abend
- Department of Internal Medicine F, Sheba Medical Center Israel, Tel Hashomer, Israel
| | | | - Hussein Mahajna
- Department of Gastroenterology, Sheba Medical Center Israel, Tel Hashomer
- Faculty of Medical and Health Sciences, Tel-Aviv University, Tel-Aviv
| | - Bella Ungar
- Department of Gastroenterology, Sheba Medical Center Israel, Tel Hashomer
- Faculty of Medical and Health Sciences, Tel-Aviv University, Tel-Aviv
| | - Shomron Ben-Horin
- Department of Gastroenterology, Sheba Medical Center Israel, Tel Hashomer
- Faculty of Medical and Health Sciences, Tel-Aviv University, Tel-Aviv
| | - Uri Kopylov
- Department of Gastroenterology, Sheba Medical Center Israel, Tel Hashomer
- Faculty of Medical and Health Sciences, Tel-Aviv University, Tel-Aviv
| | - Dan Carter
- Department of Gastroenterology, Sheba Medical Center Israel, Tel Hashomer
- Faculty of Medical and Health Sciences, Tel-Aviv University, Tel-Aviv
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Mazzawi T, Yadk A, Alghneimin N, Hmeimat S, Saleem Al-Essa M, Abed Alghafer H, Haneyah F, Alkhawaldeh H, Samara E, Ghazal B. Introducing the Arabic inflammatory bowel disease disk as a tool for assessing disability in patients with inflammatory bowel disease in Jordan. Arab J Gastroenterol 2025; 26:26-32. [PMID: 39277517 DOI: 10.1016/j.ajg.2024.01.011] [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: 01/09/2023] [Revised: 10/09/2023] [Accepted: 01/26/2024] [Indexed: 09/17/2024]
Abstract
BACKGROUND AND STUDY AIM Inflammatory bowel diseases (IBD) are chronic relapsing-remitting disorders of the gastrointestinal tract. IBD causes significant impairment in the patient's quality of life that should be assessed and monitored in a flexible and easy way. The IBD-Disability Index (IBD-DI) is the only validated tool to assess disability in IBD patients, but it is difficult to use in clinical practice. The IBD Disk is a new shortened, self-administering version of the IBD-DI that allows quick assessment of IBD patients and tracks changes in disease burden over time. However, the IBD Disk has not been used yet in clinical practice in Jordan. The aim of the study was to translate the IBD Disk to Arabic language and introduce it in clinical practice in Jordan. PATIENTS AND METHODS After translating the original IBD Disk to Arabic language, IBD patients referred to outpatient clinic or admitted to the medical department at the new Al-Hussein hospital, Al-Salt, Jordan, from September 2021 until March 2022, filled the translated IBD Disk. RESULTS A total of 50 IBD patients (52 % males) were included in the study and filled the IBD Disk. The IBD Disk was easy to complete by the patients. Energy, regulating defecation, and emotions were the most disabling domains for relapsing patients. Polygonal shape area of the mean for IBD Disk scores decreased during remission. Education & work and energy had the strongest correlation at relapse. CONCLUSION The IBD Disk is a reliable visual representation of IBD disability. In this study, a translated version of IBD Disk to Arabic language was introduced for the first time in clinical practice in Jordan. The reduction in the polygonal shape area of the scores' mean represents decreased disease burden.
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Affiliation(s)
- Tarek Mazzawi
- Department of Internal Medicine, Faculty of Medicine, Al-Balqa Applied University, Al-Salt, Jordan.
| | - Ahmad Yadk
- Department of Internal Medicine, Faculty of Medicine, Al-Balqa Applied University, Al-Salt, Jordan.
| | - Nayef Alghneimin
- Department of Internal Medicine, Faculty of Medicine, Al-Balqa Applied University, Al-Salt, Jordan.
| | - Saad Hmeimat
- Department of Internal Medicine, Faculty of Medicine, Al-Balqa Applied University, Al-Salt, Jordan.
| | - Mohammad Saleem Al-Essa
- Department of Internal Medicine, Faculty of Medicine, Al-Balqa Applied University, Al-Salt, Jordan.
| | - Haneen Abed Alghafer
- Department of Internal Medicine, Faculty of Medicine, Al-Balqa Applied University, Al-Salt, Jordan.
| | - Farah Haneyah
- Department of Internal Medicine, Faculty of Medicine, Al-Balqa Applied University, Al-Salt, Jordan.
| | - Hanan Alkhawaldeh
- Department of Internal Medicine, Faculty of Medicine, Al-Balqa Applied University, Al-Salt, Jordan.
| | - Eid Samara
- Department of Internal Medicine, Faculty of Medicine, Al-Balqa Applied University, Al-Salt, Jordan.
| | - Bandar Ghazal
- Department of Internal Medicine, Faculty of Medicine, Al-Balqa Applied University, Al-Salt, Jordan.
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Odufalu FD, Gonzalez S, Hurtado ACM, Hsiao J, Xu M, Elbuluk N. A Review of Cutaneous Extraintestinal Manifestations of Inflammatory Bowel Disease in Skin of Color. Inflamm Bowel Dis 2024:izae222. [PMID: 39340819 DOI: 10.1093/ibd/izae222] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/11/2024] [Indexed: 09/30/2024]
Abstract
The incidence of inflammatory bowel disease (IBD) is increasing in racial and ethnic minority groups. Cutaneous extraintestinal manifestations (EIMs) of IBD are well-known comorbid conditions that can occur in both active and quiescent IBD. Historically, cutaneous EIMs of IBD are described in White skin with a lack of literature describing these conditions in darker skin tones. This potentially creates a knowledge gap and awareness among providers in recognizing these conditions and offering therapy in a timely manner to non-White patients. This review aims to describe the cutaneous manifestations of IBD in a wide range of skin tones with several examples to improve awareness. With further awareness, this review will enable to provide equitable care to IBD patients with cutaneous EIMs.
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Affiliation(s)
- Florence-Damilola Odufalu
- Division of Gastroenterology & Liver Diseases, Department of Medicine, University of Southern California, Los Angeles, CA, USA
| | - Sarah Gonzalez
- School of Medicine, Wayne State University, Detroit, MI, USA
| | | | - Jennifer Hsiao
- Department of Dermatology, University of Southern California, Keck School of Medicine, Los Angeles, CA, USA
| | - Mimi Xu
- Department of Medicine, University of Southern California, Keck School of Medicine, Los Angeles, CA, USA
| | - Nada Elbuluk
- Department of Dermatology, University of Southern California, Keck School of Medicine, Los Angeles, CA, USA
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Bhol NK, Bhanjadeo MM, Singh AK, Dash UC, Ojha RR, Majhi S, Duttaroy AK, Jena AB. The interplay between cytokines, inflammation, and antioxidants: mechanistic insights and therapeutic potentials of various antioxidants and anti-cytokine compounds. Biomed Pharmacother 2024; 178:117177. [PMID: 39053423 DOI: 10.1016/j.biopha.2024.117177] [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: 05/17/2024] [Revised: 07/03/2024] [Accepted: 07/22/2024] [Indexed: 07/27/2024] Open
Abstract
Cytokines regulate immune responses essential for maintaining immune homeostasis, as deregulated cytokine signaling can lead to detrimental outcomes, including inflammatory disorders. The antioxidants emerge as promising therapeutic agents because they mitigate oxidative stress and modulate inflammatory pathways. Antioxidants can potentially ameliorate inflammation-related disorders by counteracting excessive cytokine-mediated inflammatory responses. A comprehensive understanding of cytokine-mediated inflammatory pathways and the interplay with antioxidants is paramount for developing natural therapeutic agents targeting inflammation-related disorders and helping to improve clinical outcomes and enhance the quality of life for patients. Among these antioxidants, curcumin, vitamin C, vitamin D, propolis, allicin, and cinnamaldehyde have garnered attention for their anti-inflammatory properties and potential therapeutic benefits. This review highlights the interrelationship between cytokines-mediated disorders in various diseases and therapeutic approaches involving antioxidants.
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Affiliation(s)
- Nitish Kumar Bhol
- Post Graduate Department of Biotechnology, Utkal University, Bhubaneswar, Odisha 751004, India
| | | | - Anup Kumar Singh
- National Centre for Cell Science, Savitribai Phule Pune University Campus, Ganeshkhind, Pune, India
| | - Umesh Chandra Dash
- Environmental Biotechnology Laboratory, KIIT School of Biotechnology, KIIT Deemed to be University, Bhubaneswar, Odisha, India
| | - Rakesh Ranjan Ojha
- Department of Bioinformatics, BJB (A) College, Bhubaneswar, Odisha-751014, India
| | - Sanatan Majhi
- Post Graduate Department of Biotechnology, Utkal University, Bhubaneswar, Odisha 751004, India
| | - Asim K Duttaroy
- Department of Nutrition, Institute of Medical Sciences, Faculty of Medicine, University of Oslo, Norway.
| | - Atala Bihari Jena
- National Centre for Cell Science, Savitribai Phule Pune University Campus, Ganeshkhind, Pune, India.
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Greywoode R, Larson J, Peraza J, Clark R, Allison MA, Chaudhry NA, Schnatz PF, Shadyab AH, Wallace RB, Wassertheil-Smoller S. Risk of Adverse Cardiovascular Outcomes in Postmenopausal Women with Inflammatory Bowel Disease. Dig Dis Sci 2024; 69:2586-2594. [PMID: 38684633 PMCID: PMC11258184 DOI: 10.1007/s10620-024-08348-2] [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: 06/28/2023] [Accepted: 02/08/2024] [Indexed: 05/02/2024]
Abstract
BACKGROUND Individuals with inflammatory bowel disease (IBD) who lack traditional cardiovascular disease (CVD) risk factors, such as young females, are observed to experience adverse CVD outcomes. Whether women with IBD have increased CVD risk after the menopause transition is unclear. METHODS We conducted a survival analysis of Women's Health Initiative (WHI) participants and excluded those with missing IBD diagnosis, model covariate data, follow-up data, or a baseline history of the following CVD outcomes: coronary heart disease (CHD), ischemic stroke, venous thromboembolism (VTE), peripheral arterial disease (PAD). Risk of outcomes between IBD and non-IBD women was performed using Cox proportional hazard models, stratified by WHI trial and follow-up. Models were adjusted for age, socio-demographics, comorbidities (e.g., hypertension, diabetes, hypercholesterolemia, etc.), family history, and lifestyle factors (e.g., smoking, alcohol, physical activity, body mass index, etc.). RESULTS Of 134,022 WHI participants meeting inclusion criteria, 1367 (1.0%) reported IBD at baseline. Mean baseline age was 63.4 years. After adjusting for age and other confounders, no significant difference was observed between IBD and non-IBD women for the risk of CHD (HR 0.96, 95% CI 0.73-1.24), VTE (HR 1.11, 95% CI 0.81-1.52) or PAD (HR 0.64, 95% CI 0.28-1.42). After adjusting for age, risk of ischemic stroke was significantly higher (HR 1.41, 95% CI 1.06-1.88) in IBD than non-IBD women. With further adjustment, the excess risk of ischemic stroke among IBD women was attenuated and no longer statistically significant (HR 1.31, 95% CI 0.98-1.76). CONCLUSIONS Among postmenopausal women with IBD, risk of ischemic stroke may be higher than in non-IBD women.
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Affiliation(s)
- Ruby Greywoode
- Division of Gastroenterology, Montefiore Medical Center/Albert Einstein College of Medicine, 111 East 210th St, Bronx, NY, 10467, USA.
| | - Joseph Larson
- Fred Hutchinson Cancer Research Center, Seattle, WA, USA
| | - Jellyana Peraza
- Department of Medicine, Montefiore Medical Center/Albert Einstein College of Medicine, Bronx, NY, USA
| | - Rachel Clark
- Department of Medicine, Montefiore Medical Center/Albert Einstein College of Medicine, Bronx, NY, USA
| | - Matthew A Allison
- Department of Family Medicine, University of California San Diego, La Jolla, CA, USA
| | | | - Peter F Schnatz
- Department of Obstetrics Gynecology & Internal Medicine, Reading Hospital / Tower Health & Drexel University, West Reading, PA, USA
| | - Aladdin H Shadyab
- Herbert Wertheim School of Public Health and Human Longevity Science, University of California, San Diego, La Jolla, CA, USA
| | - Robert B Wallace
- Professor Emeritus of Epidemiology and Internal Medicine, University of Iowa, Iowa City, IA, USA
| | - Sylvia Wassertheil-Smoller
- Distinguished University Professor Emerita, Department of Epidemiology & Population Health Montefiore Medical Center/Albert Einstein College of Medicine, Bronx, NY, USA
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Ma D, Li Y, Li L, Yang L. Risk factors for endoscopic postoperative recurrence in patients with Crohn's Disease: a protocol for systematic review and meta-analysis. BMC Gastroenterol 2024; 24:211. [PMID: 38918740 PMCID: PMC11197377 DOI: 10.1186/s12876-024-03301-z] [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: 01/15/2024] [Accepted: 06/20/2024] [Indexed: 06/27/2024] Open
Abstract
BACKGROUND Crohn's disease (CD) is a chronic condition characterized by a high recurrence rate after surgery, which seriously affects the quality of life of patients. Many studies have explored the risk factors for the recurrence of CD after surgery, there is a lack of meta-analysis focusing on endoscopic postoperative recurrence (ePOR) as a clinical outcome. Therefore, this paper aims to identify the risk factors for ePOR in CD patients through systematic review and meta-analysis. METHODS PubMed, Embase, Cochrane Library, and Web of Science databases were searched for related literature from inception to 17th October 2023. Two researchers independently screened the literature and extracted information. Data analysis was performed using Stata18.0. RESULTS Twenty-three papers were included, with 5 case-control studies and 18 cohort studies. The National Institutes of Health quality assessment tool rated 17 studies as good and 6 studies as fair. The sample size of the 23 studies ranged from 40 to 346, and the number of patients with ePOR ranged from 23 to 169. The results of multivariate meta-analysis showed that smoking [OR = 2.06, 95% CI (1.65, 2.57), P = 0.0001], previous ileocolonic resection [OR = 1.71, 95% CI (1.23, 2.38), P = 0.002], disease localization at ileocolic resection [OR = 2.68, 95% CI (1.38, 5.22), P = 0.004], perianal disease [OR = 1.47, 95% CI (1.07, 2.03), P = 0.017], and anastomotic scattered ulcer [OR = 3.39, 95% CI (1.83, 6.28), P = 0.001] were risk factors for ePOR in CD patients. Postoperative prophylactic medication [OR = 0.53, 95% CI (0.38,0.75), P = 0.0001] was a protective factor for ePOR in CD patients. CONCLUSIONS This systematic review identified multiple factors for ePOR in CD patients, as well as a protective factor. However, the number of articles included was limited. More high-quality clinical studies are required to further validate the conclusions. TRIAL REGISTRATION This study was registered in the International Prospective Register of Systematic Reviews (PROSPERO) (CRD42023483671).
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Affiliation(s)
- Dongchi Ma
- School of nursing, Zhejiang Chinese Medical University, 548 Bin-wen Road, Hangzhou, Zhejiang, 310053, PR China
| | - Yu Li
- School of nursing, Zhejiang Chinese Medical University, 548 Bin-wen Road, Hangzhou, Zhejiang, 310053, PR China
| | - Ling Li
- School of nursing, Zhejiang Shuren University, 8 Shuren Road, Hangzhou, Zhejiang, 310015, PR China
| | - Lili Yang
- School of nursing, Zhejiang Chinese Medical University, 548 Bin-wen Road, Hangzhou, Zhejiang, 310053, PR China.
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Mao N, Yu Y, He J, Yang Y, Liu Z, Lu Y, Wang D. Matrine Ameliorates DSS-Induced Colitis by Suppressing Inflammation, Modulating Oxidative Stress and Remodeling the Gut Microbiota. Int J Mol Sci 2024; 25:6613. [PMID: 38928319 PMCID: PMC11204106 DOI: 10.3390/ijms25126613] [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: 06/05/2024] [Revised: 06/13/2024] [Accepted: 06/14/2024] [Indexed: 06/28/2024] Open
Abstract
Matrine (MT) possesses anti-inflammatory, anti-allergic and antioxidative properties. However, the impact and underlying mechanisms of matrine on colitis are unclear. The purpose of this research was to examine the protective impact and regulatory mechanism of matrine on dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) in mice. MT alleviated DSS-induced UC by inhibiting weight loss, relieving colon shortening and reducing the disease activity index (DAI). Moreover, DSS-induced intestinal injury and the number of goblet cells were reversed by MT, as were alterations in the expression of zonula occludens-1 (ZO-1) and occludin in colon. Simultaneously, matrine not only effectively restored DSS-induced oxidative stress in colonic tissues but also reduced the production of inflammatory cytokines. Furthermore, MT could treat colitis mice by regulating the regulatory T cell (Treg)/T helper 17 (Th17) cell imbalance. We observed further evidence that MT alleviated the decrease in intestinal flora diversity, reduced the proportion of Firmicutes and Bacteroidetes, decreased the proportion of Proteobacteria and increased the relative abundance of Lactobacillus and Akkermansia in colitis mice. In conclusion, these results suggest that MT may mitigate DSS-induced colitis by enhancing the colon barrier integrity, reducing the Treg/Th17 cell imbalance, inhibiting intestinal inflammation, modulating oxidative stress and regulating the gut microbiota. These findings provide strong evidence for the development and application of MT as a dietary treatment for UC.
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MESH Headings
- Animals
- Alkaloids/pharmacology
- Gastrointestinal Microbiome/drug effects
- Oxidative Stress/drug effects
- Quinolizines/pharmacology
- Quinolizines/therapeutic use
- Dextran Sulfate
- Matrines
- Mice
- T-Lymphocytes, Regulatory/metabolism
- T-Lymphocytes, Regulatory/drug effects
- T-Lymphocytes, Regulatory/immunology
- Male
- Colitis/chemically induced
- Colitis/drug therapy
- Colitis/metabolism
- Colitis/microbiology
- Inflammation/drug therapy
- Inflammation/metabolism
- Inflammation/pathology
- Zonula Occludens-1 Protein/metabolism
- Colon/pathology
- Colon/metabolism
- Colon/drug effects
- Colon/microbiology
- Th17 Cells/drug effects
- Th17 Cells/metabolism
- Th17 Cells/immunology
- Disease Models, Animal
- Cytokines/metabolism
- Mice, Inbred C57BL
- Anti-Inflammatory Agents/pharmacology
- Anti-Inflammatory Agents/therapeutic use
- Colitis, Ulcerative/drug therapy
- Colitis, Ulcerative/chemically induced
- Colitis, Ulcerative/microbiology
- Colitis, Ulcerative/metabolism
- Colitis, Ulcerative/pathology
- Occludin/metabolism
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Affiliation(s)
- Ningning Mao
- Institute of Traditional Chinese Veterinary Medicine, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China; (N.M.); (Y.Y.); (J.H.)
- MOE Joint International Research Laboratory of Animal Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China
| | - Yaming Yu
- Institute of Traditional Chinese Veterinary Medicine, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China; (N.M.); (Y.Y.); (J.H.)
- MOE Joint International Research Laboratory of Animal Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China
| | - Jin He
- Institute of Traditional Chinese Veterinary Medicine, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China; (N.M.); (Y.Y.); (J.H.)
- MOE Joint International Research Laboratory of Animal Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China
| | - Yang Yang
- Institute of Traditional Chinese Veterinary Medicine, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China; (N.M.); (Y.Y.); (J.H.)
- MOE Joint International Research Laboratory of Animal Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China
| | - Zhenguang Liu
- Institute of Traditional Chinese Veterinary Medicine, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China; (N.M.); (Y.Y.); (J.H.)
- MOE Joint International Research Laboratory of Animal Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China
| | - Yu Lu
- Institute of Veterinary Immunology & Engineering, Jiangsu Academy of Agricultural Sciences, Nanjing 210014, China
| | - Deyun Wang
- Institute of Traditional Chinese Veterinary Medicine, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China; (N.M.); (Y.Y.); (J.H.)
- MOE Joint International Research Laboratory of Animal Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China
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10
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Bohra A, Lewis D, Segal JP, Vasudevan A, Van Langenberg DR, Niewiadomski O. Utility of panenteric capsule endoscopy for the detection of small-bowel Crohn's disease in patients with a normal magnetic resonance enterography: A prospective observational pilot study. JGH Open 2023; 7:966-973. [PMID: 38162838 PMCID: PMC10757497 DOI: 10.1002/jgh3.13013] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2023] [Revised: 11/09/2023] [Accepted: 11/12/2023] [Indexed: 01/03/2024]
Abstract
Background and Aim Capsule endoscopy allows the direct visualization of the small bowel. We examined the diagnostic utility of a new modality, namely panenteric Crohn's capsule endoscopy (CE), in detecting active small-bowel Crohn's disease (CD) in those with normal magnetic resonance enterography (MRE). Methods We prospectively recruited patients with a diagnosis of CD or suspected small-bowel CD in whom the MRE was normal. Inclusion criteria included abdominal symptoms and abnormal serum or fecal biomarkers. The primary outcome was the detection of active small-bowel CD (measured through the Lewis score [LS]). Secondary outcomes included change in Montreal classification for those with a pre-existing CD diagnosis, change in medical therapy, clinical activity, and biomarkers at baseline and 6 months, and quality-of-life measures. Results A total of 22 patients with a diagnosis of CD or suspected new diagnosis were recruited, with CE complete to the caecum in 21 and 18/21 (86%) showing evidence of active small-bowel CD (LS > 135). Of the patients with a pre-existing diagnosis of CD, 9/11 (82%) had a change in Montreal classification. At 6 months following CE, 17/18 (94%) had clinician-directed change in therapy. This correlated with an improvement in the quality of life (P < 0.05 as per the Short Inflammatory Bowel Disease Questionnaire), a reduction in the Harvey Bradshaw index (median: 7-4, P < 0.001), and favorable CRP and albumin response. Conclusion Crohn's CE is a useful diagnostic test for assessing active small-bowel CD when imaging is normal but clinical suspicion is high. Crohn's CE should be integrated into the diagnostic algorithm for small-bowel CD.
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Affiliation(s)
- Anuj Bohra
- Department of GastroenterologyBox Hill HospitalBox HillVictoriaAustralia
- Department of GastroenterologyNorthern HospitalEppingVictoriaAustralia
- Eastern Health Clinical SchoolMonash UniversityBox HillVictoriaAustralia
| | - Diana Lewis
- Department of GastroenterologyNorthern HospitalEppingVictoriaAustralia
| | - Jonathan P Segal
- Department of GastroenterologyRoyal Melbourne HospitalParkvilleVictoriaAustralia
| | - Abhinav Vasudevan
- Department of GastroenterologyBox Hill HospitalBox HillVictoriaAustralia
- Eastern Health Clinical SchoolMonash UniversityBox HillVictoriaAustralia
| | - Daniel R Van Langenberg
- Department of GastroenterologyBox Hill HospitalBox HillVictoriaAustralia
- Eastern Health Clinical SchoolMonash UniversityBox HillVictoriaAustralia
| | - Olga Niewiadomski
- Department of GastroenterologyBox Hill HospitalBox HillVictoriaAustralia
- Eastern Health Clinical SchoolMonash UniversityBox HillVictoriaAustralia
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11
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Evaristo G, Szczepanski J, Farag MS, Rubin DT, Campbell LK, Marcus VA, Lamps LW, Hart J. Crohn's Disease Features in Anastomotic Biopsies from Patients With and Without Crohn's Disease: Diagnostic and Prognostic Value. Mod Pathol 2023; 36:100325. [PMID: 37660927 DOI: 10.1016/j.modpat.2023.100325] [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: 04/30/2023] [Revised: 08/14/2023] [Accepted: 08/29/2023] [Indexed: 09/05/2023]
Abstract
Endoscopic evidence of disease activity is a critical predictor of clinical relapse in patients with Crohn's disease (CD), and histologic disease activity is evolving as a similarly important end point for patient management. However, classical morphologic features of CD may overlap with postoperative inflammatory changes, confounding the evaluation of anastomotic biopsies. There is a clear unmet need for better characterization of diagnostic and clinically significant histologic features of CD in these surgically altered sites. We evaluated ileocolonic and colocolonic/rectal anastomotic biopsies performed at 3 academic institutions in patients with and without CD. The biopsies were blindly assessed for CD histologic features and correlated to clinical and endoscopic characteristics. In CD patients, the presence of each feature was correlated with the subsequent clinical exacerbation or relapse. We obtained anastomotic biopsies from 208 patients, of which 109 were operated on for CD and 99 for another indication (neoplasia [80%], diverticular disease (11%), and other [9%]). Mean time since surgery was 10 years (0-59; 14 years for CD [1-59], 6 years for non-CD [0-33]). Endoscopic inflammation was noted in 52% of cases (68% for CD and 35% for non-CD). Microscopic inflammation was present in 74% of cases (82% for CD and 67% for non-CD). Only discontinuous lymphoplasmacytosis (P < .001) and pyloric gland metaplasia (P = .04) occurred significantly more often in CD patients. However, none of the histologic features predicted clinical disease progression. In subset analysis, the presence of histologic features of CD in nonanastomotic biopsies obtained concurrently in CD patients was significantly associated with relapse (P = .03). Due to extensive morphologic overlap between CD and postoperative changes and the lack of specific histologic features of relapse, biopsies from anastomotic sites are of no value in predicting clinical CD progression. Instead, CD activity in biopsies obtained away from anastomotic sites should be used for guiding endoscopic sampling and clinical management.
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Affiliation(s)
| | | | - Mina S Farag
- Department of Pathology, McGill University, Montreal, Quebec, Canada
| | - David T Rubin
- Inflammatory Bowel Disease Center, University of Chicago Medicine, Chicago, Ilinois
| | | | - Victoria A Marcus
- Department of Pathology, McGill University, Montreal, Quebec, Canada
| | - Laura W Lamps
- Department of Pathology, University of Michigan, Ann Arbor, Michigan
| | - John Hart
- Department of Pathology, University of Chicago, Chicago, Illinois.
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12
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Li D, Gu W, Xu H, Zhang Z, Zhao C, He C, Zhu X, Li Y. Inflammation in the peripheral blood system of Crohn's Disease. Clin Exp Med 2023; 23:2805-2812. [PMID: 36842094 DOI: 10.1007/s10238-023-01030-3] [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: 10/19/2022] [Accepted: 02/14/2023] [Indexed: 02/27/2023]
Abstract
Crohn's disease (CD) is an inflammatory bowel disease that is characterized by chronic inflammation of digestive system and has a nickname "green cancer" because of its sustained alternation of periods of flares and remissions. Here, we investigated the inflammation changes in peripheral blood system of CD patients, which are less reported in China. Peripheral blood samples of 167 CD patients and 30 healthy people, as well as their clinical information, were collected at the Second Affiliated Hospital of Soochow University. Flow cytometry was performed to analyze the ratio of CD4 T cells to CD8 T cells. Cytometric Bead Array kit was used to detect the cytokines in peripheral blood in CD patients. Moreover, the expression of inflammasomes was also detected by RT-PCR. The percentage and cell number of lymphocytes in CD patients' peripheral blood system decreased significantly, while monocytes increased remarkably. Interestingly, there was an inversion of the CD4 T cells/CD8 T cells ratio in peripheral blood of CD patients. The levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) increased significantly in CD patients' peripheral blood, and lipopolysaccharide (LPS) stimulation aggravate inflammatory response. In addition, the expression of nucleotide-binding oligomerization domain-like receptor family, pyrin domain-containing 1 (NLRP1) and NLRP3 in peripheral blood mononuclear cells (PBMC) of CD patients increased significantly after LPS stimulation. The inflammation in peripheral blood of CD patients had significant changes, including PBMC, cytokines and inflammasomes. These results are helpful to get a deeper understanding of CD and improve the efficiency of diagnosis and treatment in China.
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Affiliation(s)
- Dan Li
- Department of Clinical Laboratory, The Second Affiliated Hospital of Soochow University, Suzhou, 215004, Jiangsu, People's Republic of China
| | - Wenyong Gu
- Department of Ultrasound, The Second Affiliated Hospital of Soochow University, Suzhou, 215004, Jiangsu, People's Republic of China
| | - Han Xu
- Department of Gastroenterology, The Second Affiliated Hospital of Soochow University, Suzhou, 215004, Jiangsu, People's Republic of China
| | - Zhiru Zhang
- Department of Clinical Laboratory, The Second Affiliated Hospital of Soochow University, Suzhou, 215004, Jiangsu, People's Republic of China
| | - Chenhao Zhao
- Department of Clinical Laboratory, The Second Affiliated Hospital of Soochow University, Suzhou, 215004, Jiangsu, People's Republic of China
| | - Chunyan He
- Department of Clinical Laboratory, The Second Affiliated Hospital of Soochow University, Suzhou, 215004, Jiangsu, People's Republic of China
- Institute of Laboratory Medicine, The Second Affiliated Hospital of Soochow University, 1055 San-Xiang Road, Suzhou, 215004, Jiangsu, People's Republic of China
| | - Xueming Zhu
- Department of Clinical Laboratory, The Second Affiliated Hospital of Soochow University, Suzhou, 215004, Jiangsu, People's Republic of China.
- Institute of Laboratory Medicine, The Second Affiliated Hospital of Soochow University, 1055 San-Xiang Road, Suzhou, 215004, Jiangsu, People's Republic of China.
| | - Yang Li
- Institute of Laboratory Medicine, The Second Affiliated Hospital of Soochow University, 1055 San-Xiang Road, Suzhou, 215004, Jiangsu, People's Republic of China.
- Department of Clinical Laboratory, Children's Hospital of Soochow University, Suzhou, 215025, Jiangsu, People's Republic of China.
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13
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Asante K, Racsa P, Bloomfield A, Cornett D, Schwab P. Comparison of a second TNFi vs other biologic or targeted synthetic DMARD following an initial TNFi. J Manag Care Spec Pharm 2023; 29:1109-1118. [PMID: 37776118 PMCID: PMC10541628 DOI: 10.18553/jmcp.2023.29.10.1109] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/01/2023]
Abstract
BACKGROUND: Patients with rheumatoid arthritis, psoriasis, psoriatic arthritis, ankylosing spondylitis, Crohn's disease, or ulcerative colitis may require treatment with a biologic or targeted synthetic disease-modifying antirheumatic drug (b/tsDMARD). Often, a tumor necrosis factor inhibitor (TNFi) is the initial b/tsDMARD. The TNFi may not be effective or may not be well tolerated, so patients will opt for a different TNFi or switch to a non-TNFi b/tsDMARD. No preference for a TNFi or non-TNFi has been established and guidelines are unclear. OBJECTIVE: To evaluate effectiveness by comparing patients using a second TNFi vs a non-TNFi after initial use of TNFi based on treatment patterns and health care utilization. METHODS: This retrospective analysis used Medicare Advantage prescription drug (MAPD) plan, Medicaid, and commercial plan claims data from Humana's Research Database (Louisville, KY). The first claim for TNFi or non-TNFi (July 1, 2016, to June 30, 2018) following earlier TNFi was the index date. Patients were required to have pre-index enrollment of 6 months and 12 months post-index along with diagnosis of rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, Crohn's disease, ulcerative colitis, or psoriasis. During the 12-month follow-up, persistence to the index TNFi or non-TNFi was measured as continued therapy without a gap exceeding 45 days (81 days for intravenous infusions). Adherence was proportion of days covered at least 0.8. Addition of a nonbiologic DMARD or corticosteroid was also identified. Inpatient admissions and emergency department visits were observed. Inverse probability of treatment weights was used to balance cohorts. Logistic regression models were fit to TNFi vs non-TNFI on treatment and utilization measures. RESULTS: Of identified patients, 1,022 were indexed to a second TNFi and 1,024 were indexed to non-TNFi. Weighted cohorts were balanced, with mean age 56.5 vs 56.4 years, 70.5% vs 70.7% female sex, and 68.0% vs 67.9% MAPD plan. No differences were observed on persistence or adherence, with adjusted odds ratios (OR) of 1.05 (95% CI = 0.91-1.20) and 1.04 (0.91-1.20), respectively. No differences were observed for changes in therapy via switching to another TNFi/non-TNFi (OR = 0.93; 95% CI = 0.54-1.62), via nonbiologic DMARD addition (OR = 0.95; 95% CI = 0.83-1.11), or corticosteroid addition (OR = 1.09; 95% CI = 0.92-1.88). No differences were observed for hospitalization (OR = 1.16; 95% CI = 0.99-1.37) or emergency department visits (OR = 1.02; 95% CI = 0.89-1.18). CONCLUSIONS: No differences were found between a second TNFi vs a non-TNFi. As a result, choice of TNFi or non-TNFi following an initial TNFi may be driven by relevant patient-specific considerations. At the population level, policies that prefer either TNFi or non-TNFi appear reasonable. DISCLOSURES: The study was funded by Humana Inc. Mr Racsa is an employee of Humana Healthcare Research, Inc., a subsidiary of Humana Inc. Drs Asante and Bloomfield are employees of Humana Inc. Dr Schwab was an employee of Humana Healthcare Research, Inc., a subsidiary of Humana Inc., and is now an employee of RTI Health Solutions. Dr Cornett was an employee of Humana Inc. and is now an employee of ImmunoGen Inc.
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Affiliation(s)
- Kori Asante
- Humana Pharmacy Solutions, Humana, Louisville, KY
| | | | | | | | - Phil Schwab
- Humana Healthcare Research, Humana, Louisville, KY
- RTI Health Solutions, Research Triangle Park, NC
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14
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Bertani L, D’Alessandro C, Fornili M, Coppini F, Zanzi F, Carmisciano L, Geri F, Svizzero GB, Rosi EM, De Bernardi A, Ceccarelli L, Mumolo MG, Baglietto L, Bellini M, De Bortoli N, Costa F. Response to Ustekinumab Therapy Is Associated with an Improvement of Nutritional Status in Patients with Crohn's Disease. J Clin Med 2023; 12:6118. [PMID: 37834762 PMCID: PMC10573723 DOI: 10.3390/jcm12196118] [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: 08/15/2023] [Revised: 09/15/2023] [Accepted: 09/18/2023] [Indexed: 10/15/2023] Open
Abstract
The presence of sarcopenia has been associated with the worst outcome of Crohn's disease (CD). At present, no studies have evaluated the impact of ustekinumab (UST) in terms of its effects on body composition. The aim of this prospective study was to evaluate whether UST treatment could modify the parameters of body composition as assessed by bioelectrical impedance assay (BIA) in patients with CD. We prospectively enrolled consecutive patients with CD treated with UST, evaluating the therapeutic outcome at week 48 in terms of clinical remission and mucosal healing. BIA was performed at baseline and at week 48, assessing body cellular mass, total body water, phase angle, and body mass index. Out of 44 patients enrolled, 26 (59%) were in clinical remission and 22 (50%) achieved mucosal healing at the end of follow up. No significant differences were observed at baseline in all the BIA parameters between responders and non-responders. Phase angle increased over time in responders, while this was not observed in non-responders (test for the interaction between time and outcome, p-value = 0.009 and 0.007 for clinical remission and mucosal healing, respectively). The same differential increase was observed for body cellular mass (test for the interaction between time and outcome, p-value = 0.03 and 0.05 for clinical remission and mucosal healing, respectively). Total body water and BMI increased homogenously over time regardless of the outcomes (tests for the association with time, p-values of 0.01). To conclude, responsiveness to UST therapy seems to be associated with body composition modifications in patients with CD. In particular, the increase in phase angle in responders suggests that a significant improvement of nutritional status occurred in these patients.
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Affiliation(s)
- Lorenzo Bertani
- Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Via Roma, 67, 56100 Pisa, Italy; (C.D.); (F.C.); (F.Z.); (F.G.); (E.M.R.); (A.D.B.); (M.B.); (N.D.B.)
- Tuscany North West ASL, Department of General Surgery and Gastroenterology, Pontedera Hospital, Via Roma, 147, 56025 Pontedera, Italy
| | - Claudia D’Alessandro
- Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Via Roma, 67, 56100 Pisa, Italy; (C.D.); (F.C.); (F.Z.); (F.G.); (E.M.R.); (A.D.B.); (M.B.); (N.D.B.)
| | - Marco Fornili
- Department of Clinical and Experimental Medicine, University of Pisa, Via Roma, 67, 56100 Pisa, Italy; (M.F.); (L.C.); (L.B.)
| | - Francesca Coppini
- Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Via Roma, 67, 56100 Pisa, Italy; (C.D.); (F.C.); (F.Z.); (F.G.); (E.M.R.); (A.D.B.); (M.B.); (N.D.B.)
| | - Federico Zanzi
- Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Via Roma, 67, 56100 Pisa, Italy; (C.D.); (F.C.); (F.Z.); (F.G.); (E.M.R.); (A.D.B.); (M.B.); (N.D.B.)
| | - Luca Carmisciano
- Department of Clinical and Experimental Medicine, University of Pisa, Via Roma, 67, 56100 Pisa, Italy; (M.F.); (L.C.); (L.B.)
| | - Francesca Geri
- Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Via Roma, 67, 56100 Pisa, Italy; (C.D.); (F.C.); (F.Z.); (F.G.); (E.M.R.); (A.D.B.); (M.B.); (N.D.B.)
| | - Giovanni Baiano Svizzero
- Department of General Surgery and Gastroenterology, IBD Unit, Pisa University Hospital, Via Paradisa, 2, 56124 Pisa, Italy; (G.B.S.); (L.C.); (M.G.M.); (F.C.)
| | - Emma Maria Rosi
- Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Via Roma, 67, 56100 Pisa, Italy; (C.D.); (F.C.); (F.Z.); (F.G.); (E.M.R.); (A.D.B.); (M.B.); (N.D.B.)
| | - Alice De Bernardi
- Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Via Roma, 67, 56100 Pisa, Italy; (C.D.); (F.C.); (F.Z.); (F.G.); (E.M.R.); (A.D.B.); (M.B.); (N.D.B.)
| | - Linda Ceccarelli
- Department of General Surgery and Gastroenterology, IBD Unit, Pisa University Hospital, Via Paradisa, 2, 56124 Pisa, Italy; (G.B.S.); (L.C.); (M.G.M.); (F.C.)
| | - Maria Gloria Mumolo
- Department of General Surgery and Gastroenterology, IBD Unit, Pisa University Hospital, Via Paradisa, 2, 56124 Pisa, Italy; (G.B.S.); (L.C.); (M.G.M.); (F.C.)
| | - Laura Baglietto
- Department of Clinical and Experimental Medicine, University of Pisa, Via Roma, 67, 56100 Pisa, Italy; (M.F.); (L.C.); (L.B.)
| | - Massimo Bellini
- Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Via Roma, 67, 56100 Pisa, Italy; (C.D.); (F.C.); (F.Z.); (F.G.); (E.M.R.); (A.D.B.); (M.B.); (N.D.B.)
| | - Nicola De Bortoli
- Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Via Roma, 67, 56100 Pisa, Italy; (C.D.); (F.C.); (F.Z.); (F.G.); (E.M.R.); (A.D.B.); (M.B.); (N.D.B.)
| | - Francesco Costa
- Department of General Surgery and Gastroenterology, IBD Unit, Pisa University Hospital, Via Paradisa, 2, 56124 Pisa, Italy; (G.B.S.); (L.C.); (M.G.M.); (F.C.)
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15
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Bohra A, Mohamed G, Vasudevan A, Lewis D, Van Langenberg DR, Segal JP. The Utility of Faecal Calprotectin, Lactoferrin and Other Faecal Biomarkers in Discriminating Endoscopic Activity in Crohn's Disease: A Systematic Review and Meta-Analysis. Biomedicines 2023; 11:1408. [PMID: 37239079 PMCID: PMC10216423 DOI: 10.3390/biomedicines11051408] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2023] [Revised: 05/01/2023] [Accepted: 05/03/2023] [Indexed: 05/28/2023] Open
Abstract
INTRODUCTION Currently, faecal calprotectin (FC) is the predominate faecal biomarker utilised in clinical practice to monitor Crohn's disease (CD) activity. However, there are several potential faecal biomarkers described in the literature. We performed a meta-analysis to determine the accuracy of faecal biomarkers in discriminating endoscopic activity and mucosal healing in CD. METHODS We searched the medical literature using MEDLINE, EMBASE, and PubMed from 1978 to 8 August 2022. Descriptive statistics, including sensitivity, specificity of the primary studies, their positive and negative likelihood ratios, and their diagnostic odds ratio (DOR), were calculated. The methodological quality of the included studies was evaluated using the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS) criteria. RESULTS The search found 2382 studies, of which 33 were included for analysis after screening. FC was found to have a pooled sensitivity and specificity, DOR, and negative predictive value (NPV) in discriminating active endoscopic disease (versus inactive) of 81%, 74%, 13.93, and 0.27, respectively. Faecal lactoferrin (FL) had a pooled sensitivity and specificity, DOR, and NPV in discriminating active endoscopic disease of 75%, 80%, 13.41, and 0.34, respectively. FC demonstrated a pooled sensitivity and specificity, DOR, and NPV of 88%, 72%, 18.17, and 0.19 in predicting mucosal healing. CONCLUSION FC remains an accurate faecal biomarker. Further evaluation of the utility of novel faecal biomarkers is needed.
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Affiliation(s)
- Anuj Bohra
- Department of Gastroenterology, Eastern Health, Box Hill, Melbourne, VIC 3128, Australia
- Department of Gastroenterology, Northern Health, Epping, Melbourne, VIC 3076, Australia
| | - Ghada Mohamed
- Department of Gastroenterology, Duke University Health System, Durham, NC 27710, USA
| | - Abhinav Vasudevan
- Department of Gastroenterology, Eastern Health, Box Hill, Melbourne, VIC 3128, Australia
| | - Diana Lewis
- Department of Gastroenterology, Northern Health, Epping, Melbourne, VIC 3076, Australia
- Northern Health Clinical School, University of Melbourne, Epping, Melbourne, VIC 3076, Australia
| | | | - Jonathan P. Segal
- Department of Gastroenterology, Royal Melbourne Hospital, Parkville, Melbourne, VIC 3050, Australia
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16
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Cohen NA, Steinberg JM, Silfen A, Traboulsi C, Rodriguez TG, Singer JM, Patel S, Cohen RD, Dalal SR, Sakuraba A, Pekow J, Micic D, Rubin DT. Endo-histologic Normalization Is Achievable with Tofacitinib and Is Associated with Improved Clinical Outcomes. Dig Dis Sci 2023; 68:1464-1472. [PMID: 36242686 DOI: 10.1007/s10620-022-07716-0] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/30/2022] [Accepted: 10/05/2022] [Indexed: 12/09/2022]
Abstract
BACKGROUND Recent real-world effectiveness studies investigating tofacitinib have been encouraging. Questions remain regarding the long-term effectiveness and safety of tofacitinib, effect on endoscopic remission rates, histologic changes, and alterations in fecal calprotectin levels. METHODS This retrospective study includes consecutive patients with inflammatory bowel disease (IBD) who initiated tofacitinib therapy. We reviewed electronic medical records for demographic and clinical data, as well as all adverse events and hospitalizations. All patients receiving tofacitinib were included in the safety analysis and only patients with ulcerative colitis (UC) were included in the effectiveness analysis. RESULTS 119 patients with IBD (97 UC, 12 CD, and 10 pouchitis) seen at our center between 2014 and 2020 were included in this study. Median follow-up was 32 weeks (interquartile range (IQR) 3-252). Clinical response and remission were observed in 70% and 21%, 59% and 33%, and 49%, and 37% at weeks 8, 24, and 52, respectively. Endo-histologic healing was achieved by 11%, 25%, and 37.5% of patients at weeks 8, 24, and 52, respectively. Histologic normalization occurred as early as 24 weeks in this cohort and was achieved by 26% of patients in endoscopic remission. Overall, there were 27 (25%) adverse events with 6 (5%) resulting in treatment discontinuation. There were 11 (10%) infections, none required treatment discontinuation. Ten (10.3%) patients underwent colectomy during the follow-up period. There were no cardiovascular adverse events in the cohort during follow-up. CONCLUSION This study demonstrates the effectiveness and long-term safety of tofacitinib in patients with UC. Importantly, we show that the endpoint of endo-histologic healing is achievable with tofacitinib and can occur as early as week 8 of therapy.
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Affiliation(s)
- Nathaniel A Cohen
- University of Chicago Medicine Inflammatory Bowel Disease Center, 5841 S. Maryland Avenue, MC 4076, Chicago, IL, 60637, USA
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Joshua M Steinberg
- University of Chicago Medicine Inflammatory Bowel Disease Center, 5841 S. Maryland Avenue, MC 4076, Chicago, IL, 60637, USA
| | - Alexa Silfen
- University of Chicago Medicine Inflammatory Bowel Disease Center, 5841 S. Maryland Avenue, MC 4076, Chicago, IL, 60637, USA
| | - Cindy Traboulsi
- University of Chicago Medicine Inflammatory Bowel Disease Center, 5841 S. Maryland Avenue, MC 4076, Chicago, IL, 60637, USA
| | - Tina G Rodriguez
- University of Chicago Medicine Inflammatory Bowel Disease Center, 5841 S. Maryland Avenue, MC 4076, Chicago, IL, 60637, USA
| | - Jorie M Singer
- University of Chicago Medicine Inflammatory Bowel Disease Center, 5841 S. Maryland Avenue, MC 4076, Chicago, IL, 60637, USA
| | - Shivani Patel
- University of Chicago Medicine Inflammatory Bowel Disease Center, 5841 S. Maryland Avenue, MC 4076, Chicago, IL, 60637, USA
| | - Russell D Cohen
- University of Chicago Medicine Inflammatory Bowel Disease Center, 5841 S. Maryland Avenue, MC 4076, Chicago, IL, 60637, USA
| | - Sushila R Dalal
- University of Chicago Medicine Inflammatory Bowel Disease Center, 5841 S. Maryland Avenue, MC 4076, Chicago, IL, 60637, USA
| | - Atsushi Sakuraba
- University of Chicago Medicine Inflammatory Bowel Disease Center, 5841 S. Maryland Avenue, MC 4076, Chicago, IL, 60637, USA
| | - Joel Pekow
- University of Chicago Medicine Inflammatory Bowel Disease Center, 5841 S. Maryland Avenue, MC 4076, Chicago, IL, 60637, USA
| | - Dejan Micic
- University of Chicago Medicine Inflammatory Bowel Disease Center, 5841 S. Maryland Avenue, MC 4076, Chicago, IL, 60637, USA
| | - David T Rubin
- University of Chicago Medicine Inflammatory Bowel Disease Center, 5841 S. Maryland Avenue, MC 4076, Chicago, IL, 60637, USA.
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17
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Replacing Endoscopy with Magnetic Resonance Enterography for Mucosal Activity Assessment in Terminal Ileal Crohn’s Disease: Are We There Yet? Diagnostics (Basel) 2023; 13:diagnostics13061061. [PMID: 36980368 PMCID: PMC10046927 DOI: 10.3390/diagnostics13061061] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2023] [Revised: 02/28/2023] [Accepted: 03/07/2023] [Indexed: 03/18/2023] Open
Abstract
Crohn’s disease (CD) is a chronic immune mediated disorder that most commonly affects the small bowel and/or the large bowel. Treatment targets in CD include mucosal healing assessed via ileocolonoscopy and transmural healing assessed through cross-sectional imaging modalities such as magnetic resonance enterography (MRE). More recently, histological healing in CD has emerged as a treatment target, though it is made cumbersome given its reliance on frequent endoscopic examinations. With expert guidelines now recommending regular objective assessments as part of a treat-to-target approach, accurate non-invasive assessment will become increasingly critical. MRE has an established role in the assessment of small bowel CD, with growing data supportive of its ability in detecting disease activity at mucosal and histological levels. This could therefore potentially reduce the need for serial endoscopic assessment. Thus, this review will assess the capacity of individual MRE parameters and MRE indices for detecting mucosal and histological small bowel CD activity. Furthermore, challenging scenarios, such as CD activity detection in post-operative clinical scenarios and abnormal findings in the context of a normal ileocolonoscopy, will be explored.
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Neurath L, D'Amico F, Danese S. Emerging drugs for the treatment of moderately to severely active ulcerative colitis: review of phase II and III clinical trials. Expert Opin Emerg Drugs 2023; 28:27-42. [PMID: 36876333 DOI: 10.1080/14728214.2023.2186399] [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: 03/07/2023]
Abstract
INTRODUCTION Current therapeutic options for patients with ulcerative colitis comprise monoclonal antibodies against tumor necrosis factor (TNF), alpha4/beta7 integrin, and interleukin (IL)12/23 as well as small molecules such as tofacitinib, upadacitinib, ozanimod, and filgotinib. However, many patients fail to respond to these agents or have loss of response over time. Therefore, there is a large unmet clinical need for new therapeutic agents. AREAS COVERED Here, we review recent phase 2/3 studies in active ulcerative colitis and discuss preliminary data on the efficacy (clinical, endoscopic, and histologic remission) and safety of novel drugs including Janus kinase (JAK) inhibitors, IL23 blockers, integrin inhibitors, and S1P1R modulators. EXPERT OPINION We highlight the potential impact of these agents for the future therapeutic landscape of this disease with special emphasis on clinical impact, unmet needs, safety aspects, and advanced combination therapy.
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Affiliation(s)
- Laura Neurath
- Gastroenterology and Endoscopy, IRCCS Ospedale San Raffaele and Vita-Salute San Raffaele University, Milan, Italy
| | - Ferdinando D'Amico
- Gastroenterology and Endoscopy, IRCCS Ospedale San Raffaele and Vita-Salute San Raffaele University, Milan, Italy.,Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Italy
| | - Silvio Danese
- Gastroenterology and Endoscopy, IRCCS Ospedale San Raffaele and Vita-Salute San Raffaele University, Milan, Italy
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Zeng R, Wang J, Jiang R, Yang J, Zheng C, Wu H, Zhuo Z, Yang Q, Li J, Leung FW, Sha W, Chen H. Investigating Causality and Shared Genetic Architecture between Neurodegenerative Disorders and Inflammatory Bowel Disease. Aging Dis 2022:AD.2022.12209. [PMID: 37163440 PMCID: PMC10389839 DOI: 10.14336/ad.2022.12209] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2022] [Accepted: 12/09/2022] [Indexed: 05/12/2023] Open
Abstract
Published observational studies have revealed the connection between neurodegenerative disorders and inflammatory bowel disease (IBD), whereas the causal association remains largely unclear. Our study aims to assess the causality and identify the shared genetic architecture between neurodegenerative disorders and IBD. Two-sample Mendelian randomization analyses were performed to assess the causality between IBD and neurodegenerative disorders (amyotrophic lateral sclerosis [ALS], Alzheimer's disease [AD], Parkinson's disease [PD], and multiple sclerosis [MS]). Shared genetic loci, functional interpretation, and transcriptomic profiles were further investigated in ALS and IBD. We identified that genetic predisposition to IBD was suggestively associated with lower odds of ALS (odds ratio [OR] 0.96, 95% confidence interval [CI] 0.94 to 0.99). In contrast, IBD was not genetically associated with an increased risk of AD, PD, or MS (and vice versa). Two shared genetic loci (rs6571361 and rs7154847) were derived, and SCFD1, G2E3, and HEATR5A were further identified as novel risk genes with enriched functions related to membrane trafficking. G2E3 was differentially expressed and significantly correlated with SCFD1 in patients with ALS or IBD. Our study reveals the suggestively protective role of IBD on ALS, and does not support the causality of AD, PD, or MS on IBD (and vice versa). Our findings indicate possible shared genetic architecture and pathways between ALS and IBD. These results provide insights into the pathogenesis and therapeutics of IBD and neurodegenerative disorders.
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Affiliation(s)
- Ruijie Zeng
- Department of Gastroenterology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, China
| | - Jinghua Wang
- The Second School of Clinical Medicine, Southern Medical University, Guangzhou 510515, China
- Department of Hematology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, China
| | - Rui Jiang
- Department of Gastroenterology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, China
- School of Medicine, South China University of Technology, Guangzhou 510006, China
| | - Jie Yang
- Department of Gastroenterology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, China
| | - Chunwen Zheng
- Department of Ophthalmology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, China
| | - Huihuan Wu
- Department of Gastroenterology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, China
- School of Medicine, South China University of Technology, Guangzhou 510006, China
| | - Zewei Zhuo
- Department of Gastroenterology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, China
- School of Bioscience and Bioengineering, South China University of Technology, Guangzhou 510006, China
| | - Qi Yang
- Department of Gastroenterology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, China
| | - Jingwei Li
- Department of Gastroenterology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, China
| | - Felix W Leung
- David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, USA
- Sepulveda Ambulatory Care Center, Veterans Affairs Greater Los Angeles Healthcare System, North Hills, California, USA
| | - Weihong Sha
- Department of Gastroenterology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, China
- The Second School of Clinical Medicine, Southern Medical University, Guangzhou 510515, China
- School of Medicine, South China University of Technology, Guangzhou 510006, China
- School of Bioscience and Bioengineering, South China University of Technology, Guangzhou 510006, China
| | - Hao Chen
- Department of Gastroenterology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, China
- The Second School of Clinical Medicine, Southern Medical University, Guangzhou 510515, China
- School of Medicine, South China University of Technology, Guangzhou 510006, China
- School of Bioscience and Bioengineering, South China University of Technology, Guangzhou 510006, China
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González Delgado S, Garza-Veloz I, Trejo-Vazquez F, Martinez-Fierro ML. Interplay between Serotonin, Immune Response, and Intestinal Dysbiosis in Inflammatory Bowel Disease. Int J Mol Sci 2022; 23:ijms232415632. [PMID: 36555276 PMCID: PMC9779345 DOI: 10.3390/ijms232415632] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2022] [Revised: 12/05/2022] [Accepted: 12/06/2022] [Indexed: 12/14/2022] Open
Abstract
Inflammatory Bowel Disease (IBD) is a chronic gastrointestinal disorder characterized by periods of activity and remission. IBD includes Crohn's disease (CD) and ulcerative colitis (UC), and even though IBD has not been considered as a heritable disease, there are genetic variants associated with increased risk for the disease. 5-Hydroxytriptamine (5-HT), or serotonin, exerts a wide range of gastrointestinal effects under both normal and pathological conditions. Furthermore, Serotonin Transporter (SERT) coded by Solute Carrier Family 6 Member 4 (SLC6A4) gene (located in the 17q11.1-q12 chromosome), possesses genetic variants, such as Serotonin Transporter Gene Variable Number Tandem Repeat in Intron 2 (STin2-VNTR) and Serotonin-Transporter-linked promoter region (5-HTTLPR), which have an influence over the functionality of SERT in the re-uptake and bioavailability of serotonin. The intestinal microbiota is a crucial actor in normal human gut physiology, exerting effects on serotonin, SERT function, and inflammatory processes. As a consequence of abnormal serotonin signaling and SERT function under these inflammatory processes, the use of selective serotonin re-uptake inhibitors (SSRIs) has been seen to improve disease activity and extraintestinal manifestations, such as depression and anxiety. The aim of this study is to integrate scientific data linking the intestinal microbiota as a regulator of gut serotonin signaling and re-uptake, as well as its role in the pathogenesis of IBD. We performed a narrative review, including a literature search in the PubMed database of both review and original articles (no date restriction), as well as information about the SLC6A4 gene and its genetic variants obtained from the Ensembl website. Scientific evidence from in vitro, in vivo, and clinical trials regarding the use of selective serotonin reuptake inhibitors as an adjuvant therapy in patients with IBD is also discussed. A total of 194 articles were used between reviews, in vivo, in vitro studies, and clinical trials.
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Polilli E, Frattari A, Esposito JE, Angelini G, Di Risio A, Mazzotta E, Coladonato S, Di Iorio G, Parruti G, Tocco P. SOX-1 antibodies in a patient with Crohn's disease: a case report. BMC Neurol 2022; 22:404. [PMID: 36324062 PMCID: PMC9628059 DOI: 10.1186/s12883-022-02923-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2022] [Accepted: 10/18/2022] [Indexed: 11/22/2022] Open
Abstract
BACKGROUND The anti-SOX-1 antibodies have been mainly associated with Lambert-Eaton Myasthenic Syndrome (LETMS) and Small-Cell Lung Cancer (SCLC). In this report, we describe the interesting case of a patient with serum anti-SOX-1 antibodies and Crohn's Disease (CD) with ensuing neurological symptoms. CASE PRESENTATION A Caucasian 67-year-old female was admitted to the Emergency Department with seizures, vertigo, emesis, nausea, postural instability and recurrent falls, over a period of 10 days. She had been affected by Crohn's Disease since 1991. A CT scan failed to detect any ischemic or haemorrhagic lesion. A brain MRI revealed signs of leukoencephalopathy. Western blot analysis of her serum revealed a high titre of the onconeural antibody anti-SOX1, consistent with a neurological, cerebellar type, paraneoplastic syndrome. In spite of multiple efforts to unmask a possible underlying malignancy, no neoplastic lesion cropped up during hospitalization. Her clinical conditions progressively deteriorated, up to respiratory failure; a few days later she died, due to ensuing septic shock and Multiple Organ Failure. CONCLUSIONS Our experience may usher and reveal a new role of anti-neural antibodies, so far reckoned an early indicator of associated malignancy, suggesting that neurological syndromes associated with such antibodies may complicate also chronic Gastrointestinal (GI) diseases. As of now, testing for anti-neuronal antibodies appeared unnecessary within the diagnostic assessment of gastroenterological disorders, which may lead to overlooking incident neurologic autoimmune diseases. Further exploration of such research hypothesis in clinical grounds appears intriguing.
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Affiliation(s)
- Ennio Polilli
- grid.461844.bClinical Pathology Unit, Pescara General Hospital, Via Fonte Romana, 8, 65124 Pescara PE, Pescara, Italy
| | - Antonella Frattari
- grid.461844.bIntensive Care Unit, Pescara General Hospital, Pescara, Italy
| | - Jessica Elisabetta Esposito
- grid.461844.bClinical Pathology Unit, Pescara General Hospital, Via Fonte Romana, 8, 65124 Pescara PE, Pescara, Italy
| | - Gilda Angelini
- grid.461844.bClinical Pathology Unit, Pescara General Hospital, Via Fonte Romana, 8, 65124 Pescara PE, Pescara, Italy
| | - Annalisa Di Risio
- grid.461844.bClinical Pathology Unit, Pescara General Hospital, Via Fonte Romana, 8, 65124 Pescara PE, Pescara, Italy
| | - Elena Mazzotta
- grid.461844.bInfectious Diseases Unit, Pescara General Hospital, Pescara, Italy
| | - Simona Coladonato
- grid.461844.bInfectious Diseases Unit, Pescara General Hospital, Pescara, Italy
| | - Giancarlo Di Iorio
- grid.461844.bClinical Pathology Unit, Pescara General Hospital, Via Fonte Romana, 8, 65124 Pescara PE, Pescara, Italy
| | - Giustino Parruti
- grid.461844.bInfectious Diseases Unit, Pescara General Hospital, Pescara, Italy
| | - Pierluigi Tocco
- grid.461844.bNeurology and Stroke Unit, Pescara General Hospital, Pescara, Italy
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Impact of Endoscopic and Histologic Activity on Disease Relapse in Ulcerative Colitis. Am J Gastroenterol 2022; 117:1632-1638. [PMID: 35862833 DOI: 10.14309/ajg.0000000000001912] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/03/2022] [Accepted: 06/10/2022] [Indexed: 12/11/2022]
Abstract
INTRODUCTION Endoscopic healing is currently considered the main target in the management of ulcerative colitis (UC). There are conflicting data about the role of histology as a stricter treatment objective. We aim at evaluating the additional benefit of histologic remission over endoscopic remission. METHODS We performed a prospective observational study at the McGill University Health Center. We enrolled adult patients with UC in clinical remission for at least 3 months undergoing a colonoscopy. Endoscopic disease activity was based on the Mayo endoscopic score. Rectal biopsies were obtained, and the histologic activity was evaluated using the Geboes score (active disease defined as Geboes score ≥ 3.1) with the addition of assessing the presence of basal plasmacytosis. Patients were followed up for 12 months for disease relapse defined as a partial Mayo score of > 2. At the time of relapse or end of follow-up, all patients underwent repeat endoscopic evaluation. The primary end point was clinical relapse. RESULTS Two hundred fifty-three patients were included. The presence of basal plasmacytosis was associated with relapse (adjusted odd ratio = 2.07, 95% confidence interval [CI] 1.06-4.18, P = 0.042). Time to clinical relapse was significantly higher for patients with Mayo endoscopic score > 0 with adjusted hazard ratio = 2.65, 95% CI 1.31-5.39, and P = 0.007. Time to clinical relapse was not significantly higher for Geboes score ≥ 3.1 with adjusted hazard ratio = 1.29, 95% CI 0.67-2.49, and P = 0.45. DISCUSSION Active histologic disease did not affect time to clinical relapse in patients with UC who achieved endoscopic remission while the presence of basal plasmacytosis is associated with relapse.
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Normal gastrointestinal mucosa at biopsy and subsequent cancer risk: nationwide population-based, sibling-controlled cohort study. BMC Cancer 2022; 22:890. [PMID: 35964121 PMCID: PMC9375922 DOI: 10.1186/s12885-022-09992-5] [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: 06/14/2022] [Accepted: 08/10/2022] [Indexed: 11/10/2022] Open
Abstract
Background While individuals with normal gastrointestinal (GI) mucosa on endoscopy have a lower risk of colorectal cancer, risks of other cancers remain unexplored. Methods Through Sweden’s 28 pathology departments, we identified 415,092 individuals with a first GI biopsy with histologically normal mucosa during 1965–2016 and no prior cancer. These individuals were compared to 1,939,215 matched reference individuals from the general population. Follow-up began 6 months after biopsy, and incident cancer data were retrieved from the Swedish Cancer Register. Flexible parametric model was applied to estimate cumulative incidences and hazard ratios (HRs) for cancers. We also used full siblings (n = 441,534) as a secondary comparison group. Results During a median follow-up of 10.9 years, 40,935 individuals with normal mucosa (incidence rate: 82.74 per 10,000 person-years) and 177,350 reference individuals (incidence rate: 75.26) developed cancer. Restricting the data to individuals where follow-up revealed no cancer in the first 6 months, we still observed an increased risk of any cancer in those with a histologically normal mucosa (average HR = 1.07; 95%CI = 1.06–1.09). Although the HR for any and specific cancers decreased shortly after biopsy, we observed a long-term excess risk of any cancer, with an HR of 1.08 (95%CI = 1.05–1.12) and a cumulative incidence difference of 0.93% (95%CI = 0.61%-1.25%) at 30 years after biopsy. An elevated risk of gastric cancer, lung cancer, and hematological malignancy (including lymphoproliferative malignancy) was also observed at 20 or 30 years since biopsy. Sibling analyses confirmed the above findings. Conclusion Individuals with a histologically normal mucosa at biopsy and where follow-up revealed no cancer in the first 6 months, may still be at increased risk of cancer, although excess risks are small. Supplementary Information The online version contains supplementary material available at 10.1186/s12885-022-09992-5.
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Gelmez E, Lehr K, Kershaw O, Frentzel S, Vilchez-Vargas R, Bank U, Link A, Schüler T, Jeron A, Bruder D. Characterization of Maladaptive Processes in Acute, Chronic and Remission Phases of Experimental Colitis in C57BL/6 Mice. Biomedicines 2022; 10:biomedicines10081903. [PMID: 36009449 PMCID: PMC9405850 DOI: 10.3390/biomedicines10081903] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2022] [Revised: 08/01/2022] [Accepted: 08/02/2022] [Indexed: 11/20/2022] Open
Abstract
Inflammatory bowel disease (IBD) is a chronic recurrent inflammatory disease with unknown etiology. Dextran sulfate sodium (DSS) induced colitis is a widely used mouse model in IBD research. DSS colitis involves activation of the submucosal immune system and can be used to study IBD-like disease characteristics in acute, chronic, remission and transition phases. Insight into colon inflammatory parameters is needed to understand potentially irreversible adaptations to the chronification of colitis, determining the baseline and impact of further inflammatory episodes. We performed analyses of non-invasive and invasive colitis parameters in acute, chronic and remission phases of the DSS colitis in C57BL/6 mice. Non-invasive colitis parameters poorly reflected inflammatory aspects of colitis in chronic remission phase. We found invasive inflammatory parameters, positively linked to repeated DSS-episodes, such as specific colon weight, inflamed colon area, spleen weight, absolute cell numbers of CD4+ and CD8+ T cells as well as B cells, blood IFN-γ level, colonic chemokines BLC and MDC as well as the prevalence of Turicibacter species in feces. Moreover, microbial Lactobacillus species decreased with chronification of disease. Our data point out indicative parameters of recurrent gut inflammation in context of DSS colitis.
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Affiliation(s)
- Elif Gelmez
- Infection Immunology Group, Institute of Medical Microbiology and Hospital Hygiene, Otto-von-Guericke University, 39120 Magdeburg, Germany
| | - Konrad Lehr
- Department of Gastroenterology, Hepatology and Infectious Diseases, Section of Molecular Gastroenterology and Microbiota-Associated Diseases, Otto-von-Guericke University, 39120 Magdeburg, Germany
| | - Olivia Kershaw
- Institute of Veterinary Pathology, Freie Universität Berlin, 14163 Berlin, Germany
| | - Sarah Frentzel
- Infection Immunology Group, Institute of Medical Microbiology and Hospital Hygiene, Otto-von-Guericke University, 39120 Magdeburg, Germany
| | - Ramiro Vilchez-Vargas
- Department of Gastroenterology, Hepatology and Infectious Diseases, Section of Molecular Gastroenterology and Microbiota-Associated Diseases, Otto-von-Guericke University, 39120 Magdeburg, Germany
| | - Ute Bank
- Institute of Molecular and Clinical Immunology, Medical Faculty, Otto-von-Guericke University, 39120 Magdeburg, Germany
| | - Alexander Link
- Department of Gastroenterology, Hepatology and Infectious Diseases, Section of Molecular Gastroenterology and Microbiota-Associated Diseases, Otto-von-Guericke University, 39120 Magdeburg, Germany
| | - Thomas Schüler
- Institute of Molecular and Clinical Immunology, Medical Faculty, Otto-von-Guericke University, 39120 Magdeburg, Germany
| | - Andreas Jeron
- Infection Immunology Group, Institute of Medical Microbiology and Hospital Hygiene, Otto-von-Guericke University, 39120 Magdeburg, Germany
- Immune Regulation Group, Helmholtz Centre for Infection Research, 38124 Braunschweig, Germany
| | - Dunja Bruder
- Infection Immunology Group, Institute of Medical Microbiology and Hospital Hygiene, Otto-von-Guericke University, 39120 Magdeburg, Germany
- Immune Regulation Group, Helmholtz Centre for Infection Research, 38124 Braunschweig, Germany
- Correspondence: ; Tel.: +49-391-67-13374
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Castiglione F, Imperatore N, Testa A, de Sire R, Nardone OM, Ricciolino S, Di Luna I, Patturelli M, Villani GD, Olmo O, Rispo A. Exploring the concept of deep remission in Crohn's disease: correlation between transmural healing and biomarkers. Therap Adv Gastroenterol 2022; 15:17562848221110643. [PMID: 35898191 PMCID: PMC9310328 DOI: 10.1177/17562848221110643] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/16/2022] [Accepted: 06/14/2022] [Indexed: 02/04/2023] Open
Abstract
BACKGROUND While mucosal healing (MH) and transmural healing (TH) predict relevant clinical outcomes in Crohn's disease (CD), little is known about the real significance and clinical impact of deep remission (DR). OBJECTIVES To better explore the concept of DR, toward a direct correlation between MH, TH, and biomarkers. DESIGN Real-world observational longitudinal study to evaluate the rate of clinical remission (CR), MH and TH, and the fecal calprotectin (FC)/C-reactive protein (CRP) levels in all consecutive CD patients on biologics. METHODS A receiver operating characteristic (ROC) curve was constructed to define the best FC and CRP cut-offs associated with MH and TH. Finally, patients achieving CR, MH, and TH, in association with the target FC/CRP values, were considered in DR. RESULTS Among 118 CD patients, CR, MH, and TH were achieved in 62.7, 44.1, and 32.2%, respectively. After 2 years, the mean FC levels decreased from 494 ± 15.4 μg/g to 260 ± 354.9 μg/g (p < 0.01). Using the ROC curve analysis, an FC cut-off value of 94 μg/g was associated with both MH [sensitivity: 94.2%, specificity: 84.8%, positive predictive value (PPV): 83.05%, negative predictive value (NPV): 94.92%, area under the curve (AUC): 0.95] and TH (sensitivity: 92.1%, specificity: 70%, PPV: 64.4%, NPV: 94.9%, AUC: 0.88). CRP < 5 mg/L was associated with both MH (sensitivity: 96.1%, specificity: 62.1%, PPV: 66.7%, NPV: 95.35%, AUC: 0.85) and TH (sensitivity: 97.4%, specificity: 52.5%, PPV: 52%, NPV: 95.35%, AUC: 0.78). When considering CD patients with concomitant CR, MH, and TH associated with an FC < 94 μg/g and CRP < 5 mg/L, this association was found identified in 33 patients (27.9%). CONCLUSION An FC < 94 μg/g and a normal CRP are associated with CR, MH, and TH and could be included in the definition of DR in association. So by definition, DR could be achieved in approximately 30% of CD patients during maintenance treatment with biologics.
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Affiliation(s)
| | - Nicola Imperatore
- Gastroenterology and Endoscopy Unit, AORN Antonio Cardarelli, Naples, Italy
| | - Anna Testa
- Gastroenterology Unit, Department of Clinical Medicine and Surgery, ‘Federico II’ School of Medicine, Naples, Italy
| | - Roberto de Sire
- Gastroenterology Unit, Department of Clinical Medicine and Surgery, ‘Federico II’ School of Medicine, Naples, Italy
| | - Olga Maria Nardone
- Gastroenterology Unit, Department of Clinical Medicine and Surgery, ‘Federico II’ School of Medicine, Naples, Italy
| | - Simona Ricciolino
- Gastroenterology Unit, Department of Clinical Medicine and Surgery, ‘Federico II’ School of Medicine, Naples, Italy
| | - Imma Di Luna
- Gastroenterology Unit, Department of Clinical Medicine and Surgery, ‘Federico II’ School of Medicine, Naples, Italy
| | - Marta Patturelli
- Gastroenterology Unit, Department of Clinical Medicine and Surgery, ‘Federico II’ School of Medicine, Naples, Italy
| | - Guido Daniele Villani
- Gastroenterology Unit, Department of Clinical Medicine and Surgery, ‘Federico II’ School of Medicine, Naples, Italy
| | - Oriana Olmo
- Gastroenterology Unit, Department of Clinical Medicine and Surgery, ‘Federico II’ School of Medicine, Naples, Italy
| | - Antonio Rispo
- Gastroenterology Unit, Department of Clinical Medicine and Surgery, ‘Federico II’ School of Medicine, Naples, Italy
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Gupta S, Allegretti JR. Mimics of Crohn's Disease. Gastroenterol Clin North Am 2022; 51:241-269. [PMID: 35595413 DOI: 10.1016/j.gtc.2021.12.006] [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] [Indexed: 02/21/2023]
Abstract
Crohn's disease is a chronic inflammatory disease that can affect any portion of the gastrointestinal tract. Associated symptoms can vary based on the severity of disease, extent of involvement, presence of extraintestinal manifestations, and development of complications. Diagnosis is based on a constellation of findings. Many diseases can mimic Crohn's disease and lead to diagnostic conundrums. These include entities associated with the gastrointestinal luminal tract, vascular disease, autoimmune processes, various infections, malignancies and complications, drug- or treatment-induced conditions, and genetic diseases. Careful consideration of possible causes is necessary to establish the correct diagnosis.
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Affiliation(s)
- Sanchit Gupta
- Division of Gastroenterology, Hepatology, and Endoscopy, Brigham and Women's Hospital, 850 Boyslton Street, Suite 201, Chestnut Hill, MA 02467, USA; Harvard Medical School, 25 Shattuck Street, Boston, MA 02115, USA
| | - Jessica R Allegretti
- Division of Gastroenterology, Hepatology, and Endoscopy, Brigham and Women's Hospital, 850 Boyslton Street, Suite 201, Chestnut Hill, MA 02467, USA; Harvard Medical School, 25 Shattuck Street, Boston, MA 02115, USA.
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Dell'Avalle C, D'Amico F, Gabbiadini R, Dal Buono A, Pugliese N, Zilli A, Furfaro F, Fiorino G, Allocca M, Peyrin-Biroulet L, Danese S. JAK inhibitors in crohn's disease: ready to go? Expert Opin Investig Drugs 2022; 31:145-161. [PMID: 35164629 DOI: 10.1080/13543784.2022.2032639] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022]
Abstract
INTRODUCTION Crohn's disease (CD) is a chronic, relapsing inflammatory bowel disease that can lead to significant organ damage and impaired quality of life. To date, a considerable proportion of patients does not respond to biologic compounds. It is, therefore, necessary to find alternative options with adequate efficacy and safety profiles in order to increase the chances of obtaining an enduring remission of disease. Janus kinase (JAK) inhibitors are a new class of compounds that might well serve this purpose. The aim of our review is to report the available data from clinical trials testing these new drugs in patients suffering from CD. AREAS COVERED PubMed database and ClinicalTrials.gov website were consulted in order to find the clinical trials evaluating the efficacy and safety profiles of JAK-inhibitors in CD patients, including the following compounds: tofacitinib, filgotinib, upadacitinib, TD-1473, and Pf-06651600/Pf-06700841. EXPERT OPINION JAK-inhibitors are a promising class of oral compounds in moderate-severe CD. Further clinical trials are necessary in order to implement the available knowledge, especially on their long-term safety issues.
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Affiliation(s)
| | - Ferdinando D'Amico
- Department of Biomedical Sciences, Humanitas University, Milan, Italy.,Department of Gastroenterology and Endoscopy, IRCCS Ospedale San Raffaele and Vita-Salute San Raffaele University, Milan, Italy
| | | | - Arianna Dal Buono
- Department of Biomedical Sciences, Humanitas University, Milan, Italy
| | - Nicola Pugliese
- Department of Biomedical Sciences, Humanitas University, Milan, Italy
| | - Alessandra Zilli
- Department of Gastroenterology and Endoscopy, IRCCS Ospedale San Raffaele and Vita-Salute San Raffaele University, Milan, Italy
| | | | - Gionata Fiorino
- Department of Gastroenterology and Endoscopy, IRCCS Ospedale San Raffaele and Vita-Salute San Raffaele University, Milan, Italy
| | - Mariangela Allocca
- Department of Gastroenterology and Endoscopy, IRCCS Ospedale San Raffaele and Vita-Salute San Raffaele University, Milan, Italy
| | - Laurent Peyrin-Biroulet
- Department of Gastroenterology and Inserm Ngere U1256, University Hospital of Nancy, University of Lorraine, France
| | - Silvio Danese
- Department of Gastroenterology and Endoscopy, IRCCS Ospedale San Raffaele and Vita-Salute San Raffaele University, Milan, Italy
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Medical Treatment of Intestinal Crohn's disease. SEMINARS IN COLON AND RECTAL SURGERY 2022. [DOI: 10.1016/j.scrs.2022.100862] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
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Kwon Y, Kim ES, Choe YH, Kim MJ. Increased Demand for Therapeutic Drugs in Pediatric Ulcerative Colitis Patients With Extraintestinal Manifestations. Front Pediatr 2022; 10:853019. [PMID: 35676896 PMCID: PMC9170076 DOI: 10.3389/fped.2022.853019] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/12/2022] [Accepted: 04/21/2022] [Indexed: 11/13/2022] Open
Abstract
BACKGROUND Ulcerative colitis (UC) is a systemic inflammatory disease with a gut predominance, which may involve other organs. The presence of extraintestinal manifestation (EIM) is an important symptom for clinicians as it alters the treatment decisions. In this study, we aimed to evaluate the initial clinical presentation and disease severity of pediatric UC patients with EIMs. METHODS One hundred forty-two patients under the age of 18 years who were diagnosed with UC from January 2003 to November 2021 were included in this study. Forty-seven patients with confirmed EIMs and 95 patients without EIMs were divided into two groups and their differences were analyzed. RESULTS The most common EIM was peripheral arthritis. The disease extent at the time of diagnosis shows a higher rate of pancolitis in the EIM-positive group (65.9%) than that of the EIM-negative group (33.7%) (p < 0.001). More than 90% of EIM-positive patients had moderate to severe disease activity on the Mayo endoscopic subscore. In the EIM-positive group, the cumulative use of systemic steroids, immunosuppressants, and biological agents from diagnosis to 1 year follow-up were significantly higher than those of the EIM-negative group (p = 0.009, 0.001, and < 0.001, respectively). About 80% of patients in the EIM-negative group reached remission, but only about 50% of the EIM-positive patients reached remission (p = 0.005). The relapse occurred more frequently in the EIM-positive group than in the EIM-negative group with statistical significance (p < 0.001). CONCLUSION Pediatric UC with EIMs had higher disease severity and often manifested upper gastrointestinal tract involvement. Despite EIMs treatment, the occurrence of new EIMs was observed repeatedly. Cumulative drug demand (steroids, immunosuppressants, and biological agents) for the treatment increased steadily over time, and frequent relapses occurred despite the combinatory use of therapeutic drugs.
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Affiliation(s)
- Yiyoung Kwon
- Department of Pediatrics, Samsung Medical Center, School of Medicine, Sungkyunkwan University, Seoul, South Korea
| | - Eun Sil Kim
- Department of Pediatrics, Samsung Medical Center, School of Medicine, Sungkyunkwan University, Seoul, South Korea
| | - Yon Ho Choe
- Department of Pediatrics, Samsung Medical Center, School of Medicine, Sungkyunkwan University, Seoul, South Korea
| | - Mi Jin Kim
- Department of Pediatrics, Samsung Medical Center, School of Medicine, Sungkyunkwan University, Seoul, South Korea
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Aloi M, Cucchiara S. Crohn’s Disease. TEXTBOOK OF PEDIATRIC GASTROENTEROLOGY, HEPATOLOGY AND NUTRITION 2022:379-391. [DOI: 10.1007/978-3-030-80068-0_28] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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Lakatos PL, Kaplan GG, Bressler B, Khanna R, Targownik L, Jones J, Rahal Y, McHugh K, Panaccione R. OUP accepted manuscript. J Can Assoc Gastroenterol 2022; 5:169-176. [PMID: 35919766 PMCID: PMC9340647 DOI: 10.1093/jcag/gwac001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/12/2022] Open
Abstract
Crohn’s disease (CD) is associated with reduced quality of life, increased absenteeism and high direct medical costs resulting from frequent hospitalizations and surgeries. Tumor necrosis factor–alpha inhibitors (TNFi’s) have transformed the therapeutic landscape and enabled a shift from a symptom control to a treat-to-target strategy. The Effect of Tight Control Management on Crohn’s Disease (CALM) trial demonstrated tight control (TC), with TNFi dose changes informed by biochemical markers of inflammation, achieved higher mucosal healing rates compared with conventional management (CM) based on symptoms. A Markov model compared TC and CM strategies from the perspective of the Canadian public payer using patient-observation data from the CALM trial. A regression model estimated weekly CD Activity Index–based transition matrices over a 5-year horizon and included covariates to improve extrapolation of outcomes beyond the 48-week trial assessment period. Costs of CD-related hospitalizations, biomarker tests and adalimumab injections were sourced from public data. Other direct medical costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs) were calculated. Absenteeism was monetized and included in a sensitivity analysis. Over the 5-year time horizon, TC reduced hospitalization costs by 64% compared with CM. Other direct medical costs were reduced by 22%; adalimumab costs increased by 38%, generating an ICER of $35,168 per QALY gained. Absenteeism costs were reduced by 54%, and, when that was included in the model, TC became dominant compared with CM. Management of CD with TC is cost-effective compared with CM in Canada and is dominant if indirect costs associated with absenteeism are included. Trial registration number: NCT01235689.
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Affiliation(s)
- Peter L Lakatos
- Department of Medicine, Division of Gastroenterology, McGill University, Montreal, Quebec, Canada
| | - Gilaad G Kaplan
- Department of Medicine, Division of Gastroenterology and Hepatology, University of Calgary, Calgary, Alberta, Canada
| | - Brian Bressler
- Department of Medicine, Division of Gastroenterology, University of British Columbia, Vancouver, British Columbia, Canada
| | - Reena Khanna
- London Health Sciences Centre—University Campus, London, Ontario, Canada
| | - Laura Targownik
- Mount Sinai Hospital, Joseph and Wolf Lebovic Health Complex, Toronto, Ontario, Canada
| | | | | | - Kevin McHugh
- AbbVie Corporation, Saint-Laurent, Quebec, Canada
| | - Remo Panaccione
- Correspondence: Remo Panaccione, MD, FRCPC, Department of Medicine, Snyder Institute for Chronic Diseases and Institute of Public Health, TRW 6D32, 3280 Hospital Drive NW, Calgary, AB, T2N 4Z6, Canada, e-mail:
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Elamin S, Cohen J. Telenutrition for Inflammatory Bowel Disease: A Tipping Point for Dietary Wellness. CROHNS & COLITIS 360 2021; 3:otab017. [PMID: 34485904 PMCID: PMC8394826 DOI: 10.1093/crocol/otab017] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
Inflammatory bowel disease (IBD), Crohn’s disease and ulcerative colitis,
cause inflammation of the digestive tract. It is estimated that about three
million Americans and, globally, over six million individuals, suffer from IBD.
While most physicians, especially gastroenterologists, are experts in the
function and pathology of the gastrointestinal tract, factors such as nutrition
science education and training, bandwidth, culture, language, and the
longitudinal nature of dietary care, represent some of the barriers to receiving
optimal nutritional guidance. Remote dietary expert counseling, an emerging
solution that has been further highlighted by the COVID-19 pandemic, can improve
IBD patients’ nutritional status, avoid food triggers, and reduce the
frequency and severity of exacerbations. Inflammatory bowel disease (IBD), Crohn’s disease and ulcerative colitis,
causes inflammation of the digestive tract. Remote nutritional expert care can
improve IBD patients’ nutritional status, avoid food triggers, and reduce
the frequency and severity of exacerbations.
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Affiliation(s)
- Sami Elamin
- Hospital Medicine Unit, Department of General Internal Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA.,Harvard Medical School, Boston, Massachusetts, USA
| | - Jonah Cohen
- Harvard Medical School, Boston, Massachusetts, USA.,Center for Advanced Endoscopy, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA
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Li Y, Pan J, Zhou N, Fu D, Lian G, Yi J, Peng Y, Liu X. A random forest model predicts responses to infliximab in Crohn's disease based on clinical and serological parameters. Scand J Gastroenterol 2021; 56:1030-1039. [PMID: 34304688 DOI: 10.1080/00365521.2021.1939411] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
BACKGROUND Infliximab (IFX) has revolutionised the treatment for Crohn's disease (CD) recently, while a part of patients show no response to it at the end of the induction period. We developed a random forest-based prediction tool to predict the response to IFX in CD patients. METHODS This observational study retrospectively enrolled the patients diagnosed with active CD and received IFX treatment at the Gastroenterology Department in Xiangya Hospital of Central South University between January 2017 and December 2019. The baseline data were recorded in the beginning and were used as predictor variables to construct models to forecast the outcome of the response to IFX. RESULTS Our cohort identified a total of 174 patients finally with a response rate of 29.3% (51/174). The area under the receiver operating characteristic curve (AUC) for the model, based on the random forest was 0.90 (95%CI: 0.82-0.98), compared to the logistic regression model with AUC of 0.68 (95%CI: 0.52-0.85). The optimal cut-off value of the random forest model was 0.34 with the specificity of 0.94, the sensitivity of 0.81 and the accuracy of 0.85. We demonstrated a strong association of IFX response with the levels of complement C3 (C3), high density lipoprotein, serum albumin, Controlling Nutritional Status (CONUT) score and visceral fat area/subcutaneous fat area ratio (VSR). CONCLUSION A novel random forest model using the clinical and serological parameters of baseline data was established to identify CD patients with baseline inflammation to achieve IFX response. This model could be valuable for physicians, patients and insurers, which allows individualised therapy.
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Affiliation(s)
- Yong Li
- Department of Gastroenterology, Xiangya Hospital, Central South University, Changsha, China
| | - Jianfeng Pan
- Department of Gastroenterology, Xiangya Hospital, Central South University, Changsha, China
| | - Nan Zhou
- Department of Gastroenterology, Xiangya Hospital, Central South University, Changsha, China
| | - Dongni Fu
- Department of Gastroenterology, Xiangya Hospital, Central South University, Changsha, China
| | - Guanghui Lian
- Department of Gastroenterology, Xiangya Hospital, Central South University, Changsha, China
| | - Jun Yi
- Department of Gastroenterology, Xiangya Hospital, Central South University, Changsha, China
| | - Yu Peng
- Department of Gastroenterology, Xiangya Hospital, Central South University, Changsha, China
| | - Xiaowei Liu
- Department of Gastroenterology, Xiangya Hospital, Central South University, Changsha, China.,Hunan International Scientific and Technological Cooperation Base of Artificial Intelligence Computer Aided Diagnosis and Treatment for Digestive Disease, Xiangya Hospital, Central South University, Changsha, China
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Breitrück A, Weigel M, Hofrichter J, Sempert K, Kerkhoff C, Mohebali N, Mitzner S, Hain T, Kreikemeyer B. Smectite as a Preventive Oral Treatment to Reduce Clinical Symptoms of DSS Induced Colitis in Balb/c Mice. Int J Mol Sci 2021; 22:8699. [PMID: 34445403 PMCID: PMC8395406 DOI: 10.3390/ijms22168699] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2021] [Revised: 08/06/2021] [Accepted: 08/07/2021] [Indexed: 11/16/2022] Open
Abstract
Natural smectites have demonstrated efficacy in the treatment of diarrhea. The present study evaluated the prophylactic effect of a diosmectite (FI5pp) on the clinical course, colon damage, expression of tight junction (TJ) proteins and the composition of the gut microbiota in dextran sulfate sodium (DSS) colitis. Diosmectite was administered daily to Balb/c mice from day 1 to 7 by oral gavage, followed by induction of acute DSS-colitis from day 8 to 14 ("Control", n = 6; "DSS", n = 10; "FI5pp + DSS", n = 11). Mice were sacrificed on day 21. Clinical symptoms (body weight, stool consistency and occult blood) were checked daily after colitis induction. Colon tissue was collected for histological damage scoring and quantification of tight junction protein expression. Stool samples were collected for microbiome analysis. Our study revealed prophylactic diosmectite treatment attenuated the severity of DSS colitis, which was apparent by significantly reduced weight loss (p = 0.022 vs. DSS), disease activity index (p = 0.0025 vs. DSS) and histological damage score (p = 0.023 vs. DSS). No significant effects were obtained for the expression of TJ proteins (claudin-2 and claudin-3) after diosmectite treatment. Characterization of the microbial composition by 16S amplicon NGS showed that diosmectite treatment modified the DSS-associated dysbiosis. Thus, diosmectites are promising candidates for therapeutic approaches to target intestinal inflammation and to identify possible underlying mechanisms of diosmectites in further studies.
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Affiliation(s)
- Anne Breitrück
- Extracorporeal Immunomodulation Unit (EXIM), Fraunhofer Institute for Cell Therapy and Immunology (IZI), 18057 Rostock, Germany; (J.H.); (S.M.)
- Division of Nephrology, Department of Internal Medicine, University Medicine Rostock, 18057 Rostock, Germany
| | - Markus Weigel
- Institute of Medical Microbiology, Justus Liebig University, 35392 Giessen, Germany;
| | - Jacqueline Hofrichter
- Extracorporeal Immunomodulation Unit (EXIM), Fraunhofer Institute for Cell Therapy and Immunology (IZI), 18057 Rostock, Germany; (J.H.); (S.M.)
| | - Kai Sempert
- Queensland Brain Institute, The University of Queensland, 4072 St Lucia, Brisbane 4000, Australia;
| | - Claus Kerkhoff
- Department of Human Sciences, School of Human Sciences, University of Osnabrück, 49076 Osnabrück, Germany;
| | - Nooshin Mohebali
- Institute of Medical Microbiology, Virology and Hygiene, University Medicine Rostock, 18057 Rostock, Germany;
| | - Steffen Mitzner
- Extracorporeal Immunomodulation Unit (EXIM), Fraunhofer Institute for Cell Therapy and Immunology (IZI), 18057 Rostock, Germany; (J.H.); (S.M.)
- Division of Nephrology, Department of Internal Medicine, University Medicine Rostock, 18057 Rostock, Germany
| | - Torsten Hain
- Institute of Medical Microbiology, Justus Liebig University, 35392 Giessen, Germany;
- German Center for Infection Research (DZIF), Partner Site Giessen-Marburg-Langen, 35392 Giessen, Germany
| | - Bernd Kreikemeyer
- Institute of Medical Microbiology, Virology and Hygiene, University Medicine Rostock, 18057 Rostock, Germany;
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Caprioli F, Daperno M, Bravatà I, Brigido A, Frigerio D, Secchi O, Rispo A. Who are the patients with Crohn's disease unsuitable to receive an anti-TNFα therapy? Results from a survey of Italian physicians and literature review. Eur J Gastroenterol Hepatol 2021; 33:1082-1090. [PMID: 34213505 DOI: 10.1097/meg.0000000000002183] [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] [Indexed: 12/11/2022]
Abstract
OBJECTIVES Anti-TNFα agents have been a staple of Crohn's disease treatment for 20 years, but they have weaknesses. New treatments have more recently become available. The aim of this paper is to examine the Crohn's disease patient population for whom anti-TNF treatments are not preferred and where new mechanisms of action should be considered. METHODS A representative sample of 100 Italian physicians with documented expertise with biological treatment of moderate-to-severe Crohn's disease were interviewed. A literature review on Crohn's disease treatment was also conducted to identify patient populations for whom anti-TNFs are unsuitable. RESULTS On the basis of the interviewed physicians, about 9% of moderate-to-severe Crohn's disease patients were noneligible to anti-TNFα due to contraindication or possible risk of intolerance, while 11% had discontinued anti-TNFα treatment due to complications or intolerance/hypersensitivity. Patients with severe heart disease and at high risk of infections were more frequently considered unsuitable. The proportion of patients considered unsuitable among elderly patients and in those with recurrent infections, cancer, and other comorbidities ranged between 40 and 60%. CONCLUSIONS We provided additional quantitative and qualitative information to help identify patients who are less suitable to anti-TNF agents, who could benefit from newer biologic agents with different mechanisms of action.
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Affiliation(s)
- Flavio Caprioli
- Department of Pathophysiology and Transplantation, Università degli Studi di Milano and Gastroenterology and Endoscopy Unit, Fondazione IRCCS Cà Granda, Ospedale Policlinico di Milano, Milan
| | - Marco Daperno
- Division of Gastroenterology, Ospedale Ordine Mauriziano di Torino, Turin
| | | | | | | | | | - Antonio Rispo
- Department of Clinical Medicine and Surgery, University of Naples 'Federico II,' Naples, Italy
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Assessing adherence to objective disease monitoring and outcomes with adalimumab in a real-world IBD cohort. Dig Liver Dis 2021; 53:980-986. [PMID: 33640302 DOI: 10.1016/j.dld.2021.02.006] [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: 11/26/2020] [Revised: 02/01/2021] [Accepted: 02/02/2021] [Indexed: 12/11/2022]
Abstract
BACKGROUND Data suggests that tight objective monitoring may improve clinical outcomes in IBD. AIM To assess the adherence to serial tight objective monitoring(clinical and biomarkers) and its effect on clinical outcomes. METHODS We retrospectively reviewed the chart of 428 consecutive IBD patients started on adalimumab between January 1,2015-January 1,2019 [338 Crohn's disease(CD), 90 ulcerative colitis(UC)]. Clinical symptoms(assessed by Harvey-Bradshaw-Index,partial Mayo),C-Reactive Protein(CRP), and fecal calprotectin(FCAL) assessments were captured at treatment initiation and at 3,6,9, and12 months. Dose optimization and drug sustainability curves were plotted by Kaplan-Meier method. RESULTS Clinical evaluation was available in nearly all patients at 3(CD-UC:95-94%), 6(90-83%), 9(86-85%) and 12(96-89%) months. CRP testing frequency decreased in CD patients over time. Compliance to serial FCAL testing was low. Clinical remission at one-year was higher in patients adherent to early assessment visit at 3 months(p = 0.001 for CD and UC). Adherence to early follow-up resulted in earlier dose optimization in CD and UC patients(pLogrank=0.026 for UC & p = 0.09 for CD). Overall drug sustainability did not differ. CONCLUSION Clinical & CRP, but not FCAL, were frequently assessed in patients starting adalimumab. Adherence to early objective combined follow-up visits resulted in earlier dose optimization, improved one-year clinical outcomes but did not change drug sustainability.
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Qin Y, Yu Y, Yang C, Wang Z, Yang Y, Wang C, Zheng Q, Li D, Xu W. Atractylenolide I Inhibits NLRP3 Inflammasome Activation in Colitis-Associated Colorectal Cancer via Suppressing Drp1-Mediated Mitochondrial Fission. Front Pharmacol 2021; 12:674340. [PMID: 34335248 PMCID: PMC8320763 DOI: 10.3389/fphar.2021.674340] [Citation(s) in RCA: 30] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2021] [Accepted: 06/18/2021] [Indexed: 01/04/2023] Open
Abstract
Inflammatory bowel disease (IBD) is an important high-risk factor that promotes the occurrence and development of colon cancer. Research on the mechanism of regulating NLRP3 can provide potential targets for treating NLRP3 inflammasome–related diseases and changing the inflammatory potential of immune cells. In this study, the effects of atractylenolide I on colitis-associated CRC (caCRC) and inflammasome activation were investigated both in vivo and in vitro. Furthermore, the role of atractylenolide I on Drp1-mediated mitochondrial fission was analyzed via Western blotting and transmission electron microscopy (TEM). Moreover, the Drp1 overexpression lentiviral vector was used to study the role of Drp1 on the signaling mechanisms of atractylenolide I. Atractylenolide I treatment significantly reduced the cell viability of human HCT116 and SW480 cells and induced apoptosis, and effectively inhibited colon tumors in the AOM/DSS mouse model. The reduction of NLRP3 inflammasome activation and excessive fission of mitochondria mediated by Drp1 were associated with the administration of atractylenolide I. Upregulation of Drp1 reversed the inhibitory effect of atractylenolide I on the activation of NLRP3 inflammasomes. Overexpressing the Drp1 expression counteracted the restraint of atractylenolide I on the release of IL-1β of LPS/DSS-stimulated BMDMs. Atractylenolide I inhibited NLRP3 and caspase-1 expression in mice BMDMs, with no influence in the Drp1-overexpressed BMDMs. These results demonstrated that atractylenolide I inhibits NLRP3 inflammasome activation in colitis-associated colorectal cancer via suppressing Drp1-mediated mitochondrial fission.
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Affiliation(s)
- Yao Qin
- School of Integrated Traditional Chinese and Western Medicine, Binzhou Medical University, Yantai, China
| | - Yanwei Yu
- Yantai Hospital of Traditional Chinese Medicine, Yantai, China
| | - Chendong Yang
- Yantai Hospital of Traditional Chinese Medicine, Yantai, China
| | - Zhuien Wang
- School of Integrated Traditional Chinese and Western Medicine, Binzhou Medical University, Yantai, China
| | - Yi Yang
- School of Integrated Traditional Chinese and Western Medicine, Binzhou Medical University, Yantai, China
| | - Chongxu Wang
- School of Integrated Traditional Chinese and Western Medicine, Binzhou Medical University, Yantai, China
| | - Qiusheng Zheng
- School of Integrated Traditional Chinese and Western Medicine, Binzhou Medical University, Yantai, China
| | - Defang Li
- School of Integrated Traditional Chinese and Western Medicine, Binzhou Medical University, Yantai, China
| | - Wenjuan Xu
- School of Integrated Traditional Chinese and Western Medicine, Binzhou Medical University, Yantai, China
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Deep Analysis of the Peripheral Immune System in IBD Reveals New Insight in Disease Subtyping and Response to Monotherapy or Combination Therapy. Cell Mol Gastroenterol Hepatol 2021; 12:599-632. [PMID: 33813036 PMCID: PMC8263768 DOI: 10.1016/j.jcmgh.2021.03.012] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/01/2020] [Revised: 03/24/2021] [Accepted: 03/24/2021] [Indexed: 12/21/2022]
Abstract
BACKGROUND Inflammatory bowel disease (IBD) is a complex disease with variable presentation, progression, and response to therapies. Current disease classification is based on subjective clinical phenotypes. The peripheral blood immunophenome can reflect local inflammation, and thus we measured 39 circulating immune cell types in a large cohort of IBD and control subjects and performed immunotype:phenotype associations. METHODS We performed fluorescence-activated cell sorting or CyTOF analysis on blood from 728 Crohn's disease, 464 ulcerative colitis, and 334 non-IBD patients, with available demographics, endoscopic and clinical examinations and medication use. RESULTS We observed few immune cell types commonly affected in IBD (lowered natural killer cells, B cells, and CD45RA- CD8 T cells). Generally, the immunophenome was distinct between ulcerative colitis and Crohn's disease. Within disease subtype, there were further distinctions, with specific immune cell types associating with disease duration, behavior, and location. Thiopurine monotherapy altered abundance of many cell types, often in the same direction as disease association, while anti-tumor necrosis factor (anti-TNF) monotherapy demonstrated an opposing pattern. Concomitant use of an anti-TNF and thiopurine was not synergistic, but rather was additive. For example, thiopurine monotherapy use alone or in combination with anti-TNF was associated with a dramatic reduction in major subclasses of B cells. CONCLUSIONS We present a peripheral map of immune cell changes in IBD related to disease entity and therapies as a resource for hypothesis generation. We propose the changes in B cell subsets could affect antibody formation and potentially explain the mechanism behind the superiority of combination therapy through the impact of thiopurines on pharmacokinetics of anti-TNFs.
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Ferro JM, Oliveira Santos M. Neurology of inflammatory bowel disease. J Neurol Sci 2021; 424:117426. [PMID: 33810878 DOI: 10.1016/j.jns.2021.117426] [Citation(s) in RCA: 31] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2020] [Revised: 09/21/2020] [Accepted: 03/24/2021] [Indexed: 02/07/2023]
Abstract
Inflammatory bowel diseases (IBD) are chronic inflammatory conditions affecting the digestive system, comprising two main distinctive entities, ulcerative colitis (UC) and Crohn's disease (CD). Besides gastrointestinal manifestations, IBD causes extraintestinal manifestations in the central and peripheral nervous system. The incidence of neurological complications in IBD ranges from 0.25% to 47.5%. The pathophysiology of neurological manifestations of IBD is mostly immune mediated, but dysfunction of the brain-gut axis, arterial and venous thromboembolism, infections, nutritional deficiencies and side-effects of medications (steroids, metronidazole, sulfasalazine, anti-TNF-α, anti-integrin antibodies) are other contributory mechanisms. Patients with IBD have an increased risk of arterial and venous stroke, mainly during periods of exacerbations. Vasculitis is extremely rare. There is a bidirectional association between multiple sclerosis and IBD, with a relative risk for comorbidity of 1.54, being 1.53 for the risk of multiple sclerosis in IBD and 1.55 for the risk of IBD in multiple sclerosis patients. Anti-TNF-α therapy is contraindicated in the treatment of patients who have both IBD and multiple sclerosis. Demyelinating disorders can also be a rare complication of anti-TNF-α therapy. Optic neuritis, transverse myelitis, progressive myelopathy, central nervous system infections, epilepsy and encephalopathy are among other uncommon neurological complications. Peripheral nervous system manifestations include peripheral neuropathy, either demyelination and axonal, myasthenia gravis and polymyositis/dermatomyositis and localized forms of myositis.
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Affiliation(s)
- José M Ferro
- Serviço de Neurologia, Department of Neurological Sciences and Mental Health, Hospital de Santa Maria - CHULN, Lisboa, Portugal; Faculdade de Medicina, Universidade de Lisboa, Portugal; Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Portugal.
| | - Miguel Oliveira Santos
- Serviço de Neurologia, Department of Neurological Sciences and Mental Health, Hospital de Santa Maria - CHULN, Lisboa, Portugal; Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Portugal
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Mosli MH, Saadah OI. Metabolic bone disease in children and adolescent patients with ulcerative colitis. J Pediatr (Rio J) 2021; 97:242-247. [PMID: 32335076 PMCID: PMC9432293 DOI: 10.1016/j.jped.2020.03.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/22/2020] [Revised: 03/23/2020] [Accepted: 03/24/2020] [Indexed: 11/27/2022] Open
Abstract
OBJECTIVE Metabolic bone disease concerns a broad spectrum of conditions related to reduced bone density. Metabolic bone disease has been linked to chronic inflammatory diseases, such as ulcerative colitis. This study examines the prevalence of metabolic bone disease in ulcerative colitis patients and explores possible clinical predictors. METHOD The authors performed a retrospective study involving children and adolescents with confirmed ulcerative colitis between January 2013 and December 2018. Bone density was evaluated through a dual-energy X-ray absorptiometry scan of the spine and total body. Osteoporosis was defined as a bone mineral density Z-score of <-2 and osteopenia as a Z-score of between -1.0 and -2. RESULTS A total of 37 patients were included in this analysis, with a mean age of 13.4±3.9 years and a mean duration of illness of 2.1±2.4 years. Using lumbar spine Z-scores and total body Z-scores, osteoporosis and osteopenia were identified by dual-energy X-ray absorptiometry scan measurements in 11 patients (29.7%) and 15 patients (40.5%), and in ten patients (27%) and 13 patients (35%), respectively. Lumbar spine Z-scores were significantly positively associated with male gender (B=2.02; p=0.0001), and negatively associated with the presence of extraintestinal manifestations (B=-1.51, p=0.009) and the use of biologics (B=-1.33, p=0.004). However, total body Z-scores were positively associated with body mass index Z-scores (B=0.26, p=0.004) and duration of illness in years (B=0.35, p=0.003). CONCLUSIONS Metabolic bone disease is very common in this cohort of Saudi Arabian children and adolescents with ulcerative colitis and its occurrence appears to increase in female patients who suffer from extraintestinal manifestations.
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Affiliation(s)
- Mahmoud Hisham Mosli
- Inflammatory Bowel Disease Research Group, King Abdulaziz University, Jeddah, Saudi Arabia; Department of Internal Medicine, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Omar Ibrahim Saadah
- Department of Pediatrics, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia; Inflammatory Bowel Disease Research Group, King Abdulaziz University, Jeddah, Saudi Arabia.
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Association between Optic Neuritis and Inflammatory Bowel Disease: A Population-Based Study. J Clin Med 2021; 10:jcm10040688. [PMID: 33578895 PMCID: PMC7916645 DOI: 10.3390/jcm10040688] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2021] [Revised: 02/02/2021] [Accepted: 02/07/2021] [Indexed: 01/13/2023] Open
Abstract
Extraintestinal manifestations are common in patients with inflammatory bowel disease (IBD), and optic neuritis (ON) is a rare but severe one. This study aimed to evaluate possible factors associated with ON in patients with IBD. Adult patients with IBD who were not with concomitant ON on the index date identified from the Taiwan National Health Insurance Research Database (NHIRD) from the years 2000 to 2013 were included. A four-fold matched group was selected using age, sex and year of index date for comparison. All the patients were followed up until the development of ON or the end of the study period. Data of included patients were extracted and analyzed statistically. The mean follow-up time for all patients was 7.13 ± 5.21 years. At the study period conclusion, eight (0.18%) and five (0.003%) patients with and without IBD, respectively, had developed ON (p = 0.001). Adjusted HRs showed that patients with IBD aged between 30 and 39 years, with comorbidities including neuromyelitis optica (NMO), acute disseminated encephalomyelitis (ADEM), systemic lupus erythematosus (SLE) and with a higher Charlson Comorbidity Index, had a significantly higher risk of developing ON (all p < 0.005). Among the eight IBD patients who developed ON, only one patient was diagnosed with Crohn’s disease, the male gender was slightly dominant, and two (25%) patients received antitumor necrosis factor α (anti-TNF α) treatment for IBD. Patients with IBD have a higher risk of developing ON compared to patients without IBD. ON occurs more frequently in IBD patients aged between 30 and 39 years, with comorbidities including NMO, ADEM and SLE. Other factors besides anti-TNF α treatment for IBD are more likely associated with the development of ON.
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Dore MP, Fanciulli G, Manca A, Cocco V, Nieddu A, Murgia M, Pes GM. Clinically relevant thyroid disorders and inflammatory bowel disease are inversely related: a retrospective case-control study. Scand J Gastroenterol 2021; 56:171-176. [PMID: 33327797 DOI: 10.1080/00365521.2020.1861323] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
OBJECTIVES The risk of thyroid disorders (TDs) in inflammatory bowel disease (IBD) is still controversial. The aim of this retrospective, single-center, case-control study was to explore the association between clinically relevant functional TDs and IBD. METHODS Consecutive individuals for a total of 313 IBD patients [90 Crohn's disease (CD); 223 ulcerative colitis (UC)], and 833 individuals undergoing colonoscopy for screening without IBD were collected. In the study, subject's information on thyroid status were retrieved. Thyroid disorders were classified, according to the functional status, as hypothyroidism or hyperthyroidism. Patients with TDs (cases) were compared with 941 without (controls) according to IBD exposure. Unadjusted and adjusted odds ratios (ORs) and their 95% confidence interval (CI) were calculated. RESULTS Clinically relevant TDs were detected in 205 (17,9%) patients and the prevalence was significantly lower in IBD patients compared with subjects without (8.3% vs 12.9%; p = 0.029). After adjusting for potential confounders, a higher TDs risk was confirmed in female (OR 2.72; 95%CI 1.88‒3.92) and older subjects (OR 1.01; 95%CI 1.00‒1.03), and a lower risk in IBD (OR 0.51; 95%CI 0.34‒0.76), especially for hypothyroidism (OR 0.33; 95%CI 0.17‒0.66) in UC. Among four thyroid cancers, only one was detected in IBD patients. CONCLUSIONS Overall, in our study, the risk of TDs was lower in IBD patients. To assess routinely hormones and/or thyroid gland imaging in the absence of clinical signs or symptoms seems unnecessary in IBD patients, at least in our geographic area.
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Affiliation(s)
- Maria Pina Dore
- Dipartimento di Scienze Mediche, Chirurgiche e Sperimentali, University of Sassari, Sassari, Italy.,Baylor College of Medicine, Houston, TX, USA
| | - Giuseppe Fanciulli
- Dipartimento di Scienze Mediche, Chirurgiche e Sperimentali, University of Sassari, Sassari, Italy.,UOC di Endocrinologia, Malattie della Nutrizione e del Ricambio, AOU Sassari, Sassari, Italy
| | - Alessandra Manca
- Dipartimento di Scienze Mediche, Chirurgiche e Sperimentali, University of Sassari, Sassari, Italy
| | - Valentina Cocco
- Dipartimento di Scienze Mediche, Chirurgiche e Sperimentali, University of Sassari, Sassari, Italy
| | - Alessandra Nieddu
- Dipartimento di Scienze Mediche, Chirurgiche e Sperimentali, University of Sassari, Sassari, Italy
| | - Michele Murgia
- Dipartimento di Scienze Mediche, Chirurgiche e Sperimentali, University of Sassari, Sassari, Italy
| | - Giovanni Mario Pes
- Dipartimento di Scienze Mediche, Chirurgiche e Sperimentali, University of Sassari, Sassari, Italy
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Halawani H, Abduljabbar A, Wazzan M, Hashem DA, Baumann C, Luc A, Peyrin-Biroulet L, Saadah OI, Mosli M. Bowel Damage at Diagnosis Using the Lémann Index Score in Saudi Arabian Patients With Crohn's Disease. Cureus 2020; 12:e10912. [PMID: 33194479 PMCID: PMC7657373 DOI: 10.7759/cureus.10912] [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] [Indexed: 11/07/2022] Open
Abstract
Background Advanced bowel damage caused by Crohn’s disease (CD) in the form of strictures and penetrating lesions has been associated with future surgical resection. However, in general, the degree of bowel damage in patients with CD is not examined at the time of diagnosis, and the natural history of CD may differ phenotypically between patients from Arabic countries as compared to patients from Europe and North America. Thus, we aimed to assess the degree of structural bowel damage in Saudi Arabian CD patients at diagnosis. We used the Lémann Index (LI) score, an instrument that measures cumulative digestive tissue damage by magnetic resonance enterography (MRE) and endoscopy, to establish any possible association between the duration of symptoms and the degree of bowel damage. Method This retrospective study was conducted by reviewing the data of all CD patients following up at King Abdulaziz University Hospital (KAUH) that were investigated by endoscopy and MRE at baseline. MRE-LI was calculated by scoring previous surgery, disease location and extension, and intestinal complications. A LI score of >2.0 was set as the cut-off point for bowel damage. Descriptive statistics were used to provide an overview of demographic and clinical characteristics, and hypothesis testing was applied to identify associations. Result Eighty-three patients with CD were included in this study. Fifty point six percent (50.6%) of the cohort comprised females and the median age was 27 years. With regards to CD location and extension, 34.9% showed ileal disease (L1), 9.6% showed colonic CD (L2), whereas 55.4% had ileocolonic involvement (L3). Moreover, 48.2% of patients presented with non-complicated behavior (B1), 25.3% had at least one stricture (B2), and 26.5% showed a penetrating phenotype (B3). Perianal CD was observed in 2.4% of subjects and 62.7% had undergone bowel resection. Mean LI was 2.4 (±2.6) with 34 patients (39.8%) exhibiting an LI score indicative of advanced bowel damage at the time of diagnosis. The duration of symptoms did not correlate with the degree of bowel damage according to the LI score. Conclusion A significant proportion of patients with CD presented with advanced bowel damage at the time of diagnosis, suggesting that a severe form of CD may be endemic in Saudi Arabia.
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Affiliation(s)
| | | | | | | | - Cedric Baumann
- Gastroenterology, University Hospital of Nancy, France, FRA
| | - Amandine Luc
- Gastroenterology, University Hospital of Nancy, France, FRA
| | | | - Omar I Saadah
- Pediatric Gastroenterology, King Abdulaziz University Hospital, Jeddah, SAU
| | - Mahmoud Mosli
- Gastroenterology, King Abdulaziz University Hospital, Jeddah, SAU
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D'Arcangelo G, Aloi M. Treat-to-Target in Pediatric Inflammatory Bowel Disease: What Does the Evidence Say? Paediatr Drugs 2020; 22:463-472. [PMID: 32572841 DOI: 10.1007/s40272-020-00406-2] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
The traditional management of inflammatory bowel disease, based on treatment intensification guided by clinical activity alone, has been revised in the last 10 years and a treat-to-target approach has been proposed and is currently under evaluation as a disease-modifying strategy. Treat-to-target focuses on objective and scheduled measures to monitor intestinal damage, with consequent therapeutic adjustments in case of failure to achieve pre-defined targets. Identification of targets has been set out by the Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE) committee in 2015. Mucosal healing is universally accepted as the main target both in Crohn's disease and ulcerative colitis, given its proven association with better long-term outcomes than clinical remission alone. Equally important is to ensure patients' clinical remission and improve patient-reported outcomes. Transmural healing (for Crohn's disease) and histological remission (for ulcerative colitis), listed as adjunctive targets, are likely to become primary targets in the near future. The ultimate goal of this approach is to modify the natural history of inflammatory bowel diseases by trying to block bowel damage progression, with interventions in the pre-clinical stage. In this review, we will discuss the current recommended therapeutic targets, as well as those that are considered adjunctive targets, with a focus on the limited pediatric literature available. Prospective long-term trials are warranted in order to identify the most appropriate target for the pediatric population and its specific issues. Identification of reliable predictors of disease course, outcome, and response to treatment will help to individually adapt each step of this monitoring algorithm and consequent therapeutic decision.
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Affiliation(s)
- Giulia D'Arcangelo
- Department of Women's and Children's Health, Pediatric Gastroenterology and Liver Unit, Sapienza University of Rome, Viale Regina Elena 324, 00161, Rome, Italy
| | - Marina Aloi
- Department of Women's and Children's Health, Pediatric Gastroenterology and Liver Unit, Sapienza University of Rome, Viale Regina Elena 324, 00161, Rome, Italy.
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Adherence to Medical Treatment in Inflammatory Bowel Disease Patients from a Referral Center in Bahia-Brazil. BIOMED RESEARCH INTERNATIONAL 2020; 2020:5269493. [PMID: 33029512 PMCID: PMC7537680 DOI: 10.1155/2020/5269493] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 07/29/2020] [Revised: 09/03/2020] [Accepted: 09/19/2020] [Indexed: 11/18/2022]
Abstract
Background/Aims. Identify the degree of adherence to drug therapy in patients with inflammatory bowel diseases followed up at a referral center in Bahia-Brazil. Methods. Observational, analytical, and cross-sectional studies carried out from June/2017 to July/2018, with questionnaire application and medical record review at a referral center in inflammatory bowel diseases in Salvador, Bahia. The Morisky Green Levine Scale was applied to assess adherence. Mean, standard deviation, and frequency analyses were performed using the statistical package SPSS, and chi-square was used to evaluate the association between categorical variables and adherence degree to treatment. Significant associations were considered with p<0.05. Results. 302 patients with inflammatory bowel diseases were included. Nonadherence was highlighted in the sample. Most part of the study population was female, declared themselves to be mixed race, claimed to be from urban areas, and married. Nonadherence was more frequent than adherence in most sociodemographic variables of the present study. Nonadherence also stood out among the clinical variables, such as disease activity, drug side effect, and use of more than two additional medications. The association between all studied variables and adherence degree to treatment, considering the general sample, did not show statistical significance. When Crohn’s disease and ulcerative colitis patients were evaluated separately, a statistically significant association between nonadherence and female patients with ulcerative colitis was observed. Conclusions. The high frequency of nonadherence was observed in the studied sample. Female gender was associated to nonadherence in the subpopulation with ulcerative colitis.
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Zheng DD, Mantis J, Gurung DO, Abrudescu A. Sustained Remission of Lupus Panniculitis Treated With Hydroxychloroquine in a Patient With Crohn’s Disease: A Case Report. Cureus 2020; 12:e10455. [PMID: 33072463 PMCID: PMC7560489 DOI: 10.7759/cureus.10455] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022] Open
Abstract
Extraintestinal manifestations (EIM) in inflammatory bowel disease (IBD) are common including cutaneous manifestations that either precede or follow manifestations of IBD. Cutaneous manifestations of IBD include erythema nodosum, pyoderma gangrenosum, oral lesions, and Sweet’s syndrome. Cutaneous manifestations of IBD tend to recur and extensive cases may require maintenance management with immunomodulators or biologics. However, the complications and adverse effects of long-term therapy with immunosuppressive agents are numerous and need to be considered before their initiation. We report a case of a Crohn’s disease patient with recurrent and debilitating cutaneous manifestation of lupus panniculitis that had sustained remission with hydroxychloroquine.
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Vajravelu RK, Copelovitch L, Osterman MT, Scott FI, Mamtani R, Lewis JD, Denburg MR. Inflammatory Bowel Diseases Are Associated With an Increased Risk for Chronic Kidney Disease, Which Decreases With Age. Clin Gastroenterol Hepatol 2020; 18:2262-2268. [PMID: 31683056 PMCID: PMC7569504 DOI: 10.1016/j.cgh.2019.10.043] [Citation(s) in RCA: 34] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/03/2019] [Revised: 10/09/2019] [Accepted: 10/21/2019] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS It is not clear what factors affect risk of chronic kidney disease (CKD) in patients with inflammatory bowel disease (IBD); increased risk has been inconsistently associated with use of 5-aminosalicylates (5-ASAs). We aimed to calculate the relative hazard of CKD among patients with IBD, adjusted for CKD risk factors, and to determine whether IBD medications are associated with change in estimated glomerular filtration rate (eGFR). METHODS We performed a retrospective cohort study of data from The Health Improvement Network. Patients with IBD (n = 17,807) were matched for age, sex, and practice to individuals without IBD (n = 63,466). The relative hazard of CKD, stages 3 through 5D, in patients with IBD was calculated using a Cox proportional hazards model adjusted for common CKD risk factors. We also evaluated the association of 5-ASAs, azathioprine, and methotrexate with change in eGFR using a longitudinal model. RESULTS After we controlled for risk factors associated with CKD, we found IBD to be associated with development of CKD in patients 16-77 years old. As patient age increased, the adjusted hazard ratio for CKD decreased monotonically, from 7.88 (95% CI, 2.56-24.19) at age 16 to 1.13 (95% CI, 1.01-1.25) at age 77. In the longitudinal analysis, exposure to 5-ASAs or methotrexate was not associated with change in eGFR, whereas azathioprine was associated with a slightly higher eGFR (0.32 mL/min/1.73 m2; 95% CI, 0.16-0.48). CONCLUSIONS In a retrospective study of more than 80,000 persons, we found that IBD is associated with increased risk of CKD, and the hazard ratio is highest among younger patients. Commonly used non-biologic therapeutic agents were not associated with lower eGFR.
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Affiliation(s)
- Ravy K Vajravelu
- Division of Gastroenterology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania; Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
| | - Lawrence Copelovitch
- Division of Nephrology, Department of Pediatrics, The Children's Hospital of Philadelphia, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania
| | - Mark T Osterman
- Division of Gastroenterology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania
| | - Frank I Scott
- Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania; Division of Gastroenterology, Department of Medicine, University of Colorado Denver School of Medicine, Aurora, Colorado
| | - Ronac Mamtani
- Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania; Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania
| | - James D Lewis
- Division of Gastroenterology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania; Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania
| | - Michelle R Denburg
- Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania; Division of Nephrology, Department of Pediatrics, The Children's Hospital of Philadelphia, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania
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Zacharopoulou E, Craviotto V, Fiorino G, Furfaro F, Zilli A, Gilardi D, Peyrin-Biroulet L, Danese S, Allocca M. Targeting the gut layers in Crohn's disease: mucosal or transmural healing? Expert Rev Gastroenterol Hepatol 2020; 14:775-787. [PMID: 32515627 DOI: 10.1080/17474124.2020.1780914] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
INTRODUCTION Although the landmark of Crohn's Disease (CD) is the transmural inflammation, mucosal healing (MH), which is assessed by colonoscopy, is currently the gold standard of CD management. Transmural healing (TH) is a new concept evaluated by cross-sectional imaging (CSI) techniques, such as bowel ultrasound (US), computed tomography enterography (CTE), and magnetic resonance enterography (MRE). Little is known about the clinical significance of persisting mural disease and the predictive value of complete TH. AREAS COVERED The authors reviewed the available literature on TH and its meaning as predictor of long-term outcomes in CD, to explore if TH may be a better target compared to MH in CD patients, in terms of disease outcome, such as medication changes, hospitalization, or surgery. EXPERT OPINION Some evidence suggests that achieving TH has a predictive value in CD management and correlates with better disease outcome than MH, although existing studies are few and with limitations. A definitive definition of TH is not yet established and the frequency or the preferred modality of TH evaluation remains unclear. Implementing TH in treat-to-target approach may enable stricter disease monitoring with noninvasive methods and finally change the disease course, preventing irreversible bowel damage.
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Affiliation(s)
| | - Vincenzo Craviotto
- IBD Centre, Humanitas Clinical and Research Centre, IRCCS , Milan, Italy
| | - Gionata Fiorino
- IBD Centre, Humanitas Clinical and Research Centre, IRCCS , Milan, Italy.,Department of Biomedical Sciences, Humanitas University , Milan, Italy
| | - Federica Furfaro
- IBD Centre, Humanitas Clinical and Research Centre, IRCCS , Milan, Italy
| | - Alessandra Zilli
- IBD Centre, Humanitas Clinical and Research Centre, IRCCS , Milan, Italy
| | - Daniela Gilardi
- IBD Centre, Humanitas Clinical and Research Centre, IRCCS , Milan, Italy
| | - Laurent Peyrin-Biroulet
- Department of Gastroenterology and Inserm U954, University Hospital of Nancy, Lorraine University , Nancy, France
| | - Silvio Danese
- IBD Centre, Humanitas Clinical and Research Centre, IRCCS , Milan, Italy.,Department of Biomedical Sciences, Humanitas University , Milan, Italy
| | - Mariangela Allocca
- IBD Centre, Humanitas Clinical and Research Centre, IRCCS , Milan, Italy.,Department of Biomedical Sciences, Humanitas University , Milan, Italy
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de Campos Silva EF, Baima JP, de Barros JR, Tanni SE, Schreck T, Saad-Hossne R, Sassaki LY. Risk factors for ulcerative colitis-associated colorectal cancer: A retrospective cohort study. Medicine (Baltimore) 2020; 99:e21686. [PMID: 32769938 PMCID: PMC7593060 DOI: 10.1097/md.0000000000021686] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023] Open
Abstract
Inflammatory bowel disease is associated with an increased risk of colorectal cancer. The study aims to identify the risk factors for ulcerative colitis-colorectal cancer and to perform a survival curve analysis of the outcome.This retrospective cohort study included 254 patients from March 2016 to October 2017. Age, age at diagnosis, follow-up time, smoking status, and family history of colorectal cancer were analyzed as risk factors for colorectal cancer.The mean patient age was 46.6 ± 16.9 years; 5.5% of the patients were smokers and 49.6% had pancolitis. Six patients (2.36%) had colorectal cancer, which was associated with age at diagnosis (odds/hazard ratio 1.059 [95% confidence interval: 1.001-1.121]; P = .04), family history of colorectal cancer (12.992 [1.611-104.7]; P = .02), and follow-up time (0.665 [0.513-0.864]; P = .002). Active smoking was the main identified risk factor, after both logistic (8.477 [1.350-53.232]; P = .02) and Cox proportional-hazards (32.484 [2.465-428.1]; P = .008) regression analysis. The risk of colorectal cancer was 3.17% at 10 years and 4.26% at 20 years of follow-up.Active smoking and family history were identified as risk factors for colorectal cancer. These findings should aid the early identification of patients who require vigorous surveillance, and prevent exposure to risk factors.
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Affiliation(s)
| | - Julio Pinheiro Baima
- Department of Internal Medicine, São Paulo State University (UNESP), Medical School, Botucatu, Brazil
| | | | - Suzana Erico Tanni
- Department of Internal Medicine, São Paulo State University (UNESP), Medical School, Botucatu, Brazil
| | - Thomas Schreck
- OTH Regensburg. Faculty of Business Studies, Regensburg, Germany
| | - Rogerio Saad-Hossne
- Department of Surgery, São Paulo State University (UNESP), Medical School, Botucatu, Brazil
| | - Ligia Yukie Sassaki
- Department of Internal Medicine, São Paulo State University (UNESP), Medical School, Botucatu, Brazil
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Akkol EK, Karpuz B, Sobarzo-Sánchez E, Khan H. A phytopharmacological overview of medicinal plants used for prophylactic and treatment of colitis. Food Chem Toxicol 2020; 144:111628. [PMID: 32738379 DOI: 10.1016/j.fct.2020.111628] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2020] [Revised: 06/26/2020] [Accepted: 07/14/2020] [Indexed: 12/26/2022]
Abstract
Inflammatory bowel diseases are chronic diseases that develop on the genetic background. They are characterized by an idiopathic, chronic course and periods of activation and remission. However, genetic and environmental factors are thought to play a role in its pathogenesis. Significant improvements in treatment strategies have been witnessed. Depending on the severity of the disease, mesalamine, immunosuppressants, anti-TNF, anti-integrin, Janus kinase inhibitors, and thiopurines can be used for treatment. However, these treatments have side effects such as headache, dizziness, nausea, loss of appetite, hair loss, gas, vomiting, rash, fever, and decreased white blood cell count. The search for treatment that may be a safer alternative, immunomodulatory, and immunosuppressive therapy has gained importance nowadays. Herbal medicine is preferred to treat a wide range of acute and chronic gastrointestinal diseases, including ulcerative colitis. Preclinical and clinical studies show that plants are promising in terms of their use in treating pathological conditions. The effectiveness of plants in treating ulcerative colitis has been determined. However, more studies are needed to explore the long-term effects of these herbal medicines. The present review presents information on medicinal plants and phytochemicals reported for use or potential of application in ulcerative colitis, a type of inflammatory bowel diseases.
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Affiliation(s)
- Esra Küpeli Akkol
- Department of Pharmacognosy, Faculty of Pharmacy, Gazi University, Etiler, 06330, Ankara, Turkey.
| | - Büşra Karpuz
- Department of Pharmacognosy, Faculty of Pharmacy, Gazi University, Etiler, 06330, Ankara, Turkey
| | - Eduardo Sobarzo-Sánchez
- Instituto de Investigación en Salud, Facultad de Ciencias de la Salud, Universidad Central de Chile, 8330507, Santiago, Chile; Department of Organic Chemistry, Faculty of Pharmacy, University of Santiago de Compostela, 15782, Santiago de Compostela, Spain.
| | - Haroon Khan
- Department of Pharmacy, Abdul Wali Khan University Mardan, 23200, Pakistan.
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