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Ralston MR, McCreath G, Lees ZJ, Salt IP, Sim MA, Watson MJ, Freeman DJ. Beyond body mass index: exploring the role of visceral adipose tissue in intensive care unit outcomes. BJA OPEN 2025; 14:100391. [PMID: 40223920 PMCID: PMC11986990 DOI: 10.1016/j.bjao.2025.100391] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/20/2024] [Accepted: 02/11/2025] [Indexed: 04/15/2025]
Abstract
Obesity is a worldwide health crisis and poses significant challenges in critical care. Many studies suggest an 'obesity paradox', in which obesity, defined by body mass index (BMI), is associated with better outcomes. However, the inability of BMI to discriminate between fat and muscle or between visceral adipose tissue and subcutaneous adipose tissue, limits its prediction of metabolic ill health. We suggest that the 'obesity paradox' may be more reflective of the limitations of BMI than the protective effect of obesity. We explore the biological processes leading to visceral fat accumulation, and the evidence linking it to outcomes in critical illness. In the 'spillover' hypothesis of adipose tissue expansion, caloric excess and impaired expansion of storage capacity in the subcutaneous adipose tissue lead to accumulation of visceral adipose tissue. This is associated with a chronic inflammatory state, which is integral to the link between visceral adiposity, type 2 diabetes mellitus, and ischaemic heart disease. We review the current evidence on visceral adiposity and critical illness outcomes. In COVID-19, increased visceral adipose tissue, irrespective of BMI, is associated with more severe disease. This is mirrored in acute pancreatitis, suggesting visceral adiposity is linked to poorer outcomes in some hyperinflammatory conditions. We suggest that visceral adiposity's chronic inflammatory state may potentiate acute inflammation in conditions such as COVID-19 and acute pancreatitis. Further work is required to investigate other critical illnesses, especially sepsis and acute respiratory distress syndrome, in which current evidence is scarce. This may give further insights into pathophysiology and inform tailored treatment and nutrition strategies based on body fat distribution.
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Affiliation(s)
- Maximilian R. Ralston
- School of Cardiovascular & Metabolic Health, University of Glasgow, Glasgow, UK
- Academic Unit of Anaesthesia, Critical Care & Perioperative Medicine, University of Glasgow, Glasgow, UK
| | - Gordan McCreath
- Academic Unit of Anaesthesia, Critical Care & Perioperative Medicine, University of Glasgow, Glasgow, UK
| | - Zoe J. Lees
- School of Cardiovascular & Metabolic Health, University of Glasgow, Glasgow, UK
| | - Ian P. Salt
- School of Molecular Biosciences, University of Glasgow, Glasgow, UK
| | - Malcolm A.B. Sim
- Academic Unit of Anaesthesia, Critical Care & Perioperative Medicine, University of Glasgow, Glasgow, UK
- Department of Critical Care, Queen Elizabeth University Hospital, Glasgow, UK
| | - Malcolm J. Watson
- School of Medicine, Dentistry & Nursing, University of Glasgow, Glasgow, UK
- Department of Anaesthesia, Queen Elizabeth University Hospital, Glasgow, UK
| | - Dilys J. Freeman
- School of Cardiovascular & Metabolic Health, University of Glasgow, Glasgow, UK
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Ratajczak-Pawłowska AE, Szymczak-Tomczak A, Hryhorowicz S, Zawada A, Skoracka K, Rychter AM, Skrzypczak-Zielińska M, Słomski R, Dobrowolska A, Krela-Kaźmierczak I. Relationship of visfatin with obesity and osteoporosis in patients with inflammatory bowel disease: a narrative review. Front Immunol 2025; 16:1533955. [PMID: 40170859 PMCID: PMC11959099 DOI: 10.3389/fimmu.2025.1533955] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2024] [Accepted: 02/21/2025] [Indexed: 04/03/2025] Open
Abstract
Background Inflammatory bowel disease (IBD) is an increasingly prevalent condition in developed countries. Alongside the growing number of patients, there is a rising incidence of disease-related complications, including osteoporosis. While well-established risk factors for low bone mineral density in IBD-such as low body mass or steroid therapy-are widely recognized, other contributing factors warrant further investigation. One such factor is visfatin, a proinflammatory adipokine encoded by the NAMPT gene. Objectives This review aimed to explore the association between visfatin level, bone health, and obesity among patients with inflammatory bowel disease. Key findings Although visfatin is primarily associated with metabolic syndrome, it may also influence bone mineral density by affecting osteoblast and osteoclast differentiation and function. Additionally, some studies have identified a correlation between visfatin levels and bone mineral density. A deeper understanding of visfatin's role in osteoporosis development may contribute to the identification of novel therapeutic strategies. Therefore, lower bone mineral density in inflammatory bowel disease may be associated with obesity and visfatin levels. However, visfatin concentrations depend on many factors, including genetics, immunology, and nutritional factors, which may affect visfatin levels. Implications Current research highlights visfatin as both a potential biomarker and a therapeutic target for osteoporosis treatment. Nevertheless, limited studies have specifically examined the relationship between visfatin and bone mineral density in IBD. Further research is required to clarify this association and to explore how variations in visfatin levels impact bone density in IBD patients.
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Affiliation(s)
- Alicja Ewa Ratajczak-Pawłowska
- Department of Gastroenterology, Dietetics and Internal Diseases, Poznan University of Medical Sciences, Poznan, Poland
- Laboratory of Nutrigenetics, Department of Gastroenterology, Dietetics and Internal Diseases, Poznan University of Medical Sciences, Poznan, Poland
| | - Aleksandra Szymczak-Tomczak
- Department of Gastroenterology, Dietetics and Internal Diseases, Poznan University of Medical Sciences, Poznan, Poland
| | - Szymon Hryhorowicz
- Institute of Human Genetics, Polish Academy of Sciences Poznan, Poznan, Poland
| | - Agnieszka Zawada
- Department of Gastroenterology, Dietetics and Internal Diseases, Poznan University of Medical Sciences, Poznan, Poland
| | - Kinga Skoracka
- Department of Gastroenterology, Dietetics and Internal Diseases, Poznan University of Medical Sciences, Poznan, Poland
- Doctoral School, Poznan University of Medical Sciences, Poznan, Poland
| | - Anna Maria Rychter
- Department of Gastroenterology, Dietetics and Internal Diseases, Poznan University of Medical Sciences, Poznan, Poland
- Laboratory of Nutrigenetics, Department of Gastroenterology, Dietetics and Internal Diseases, Poznan University of Medical Sciences, Poznan, Poland
| | | | - Ryszard Słomski
- Institute of Medical Sciences, College of Social and Media Culture in Torun, Torun, Poland
- Laboratory of Molecular Genetics, Poznan, Poland
| | - Agnieszka Dobrowolska
- Department of Gastroenterology, Dietetics and Internal Diseases, Poznan University of Medical Sciences, Poznan, Poland
| | - Iwona Krela-Kaźmierczak
- Department of Gastroenterology, Dietetics and Internal Diseases, Poznan University of Medical Sciences, Poznan, Poland
- Laboratory of Nutrigenetics, Department of Gastroenterology, Dietetics and Internal Diseases, Poznan University of Medical Sciences, Poznan, Poland
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Li X, Hu C, Wang H, Lin Y, Li J, Cui E, Zhuang X, Li J, Lu J, Zhang R, Wang Y, Peng Z, Sun C, Li Z, Chen M, Shi L, Mao R, Huang B, Feng ST. AI-based fingerprint index of visceral adipose tissue for the prediction of bowel damage in patients with Crohn's disease. iScience 2024; 27:111022. [PMID: 39635135 PMCID: PMC11615179 DOI: 10.1016/j.isci.2024.111022] [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: 04/22/2024] [Revised: 06/30/2024] [Accepted: 09/20/2024] [Indexed: 12/07/2024] Open
Abstract
The fingerprint features of visceral adipose tissue (VAT) are intricately linked to bowel damage (BD) in patients with Crohn's disease (CD). We aimed to develop a VAT fingerprint index (VAT-FI) using radiomics and deep learning features extracted from computed tomography (CT) images of 1,135 CD patients across six hospitals (training cohort, n = 600; testing cohort, n = 535) for predicting BD, and to compare it with a subcutaneous adipose tissue (SAT)-FI. VAT-FI exhibited greater predictive accuracy than SAT-FI in both training (area under the receiver operating characteristic curve [AUC] = 0.822 vs. AUC = 0.745, p = 0.019) and testing (AUC = 0.791 vs. AUC = 0.687, p = 0.019) cohorts. Multivariate logistic regression analysis highlighted VAT-FI as the sole significant predictor (training cohort: hazard ratio [HR] = 1.684, p = 0.012; testing cohort: HR = 2.649, p < 0.001). Through Shapley additive explanation (SHAP) analysis, we further quantitatively elucidated the predictive relationship between VAT-FI and BD, highlighting potential connections such as Radio479 (wavelet-HLH-first-order standard deviation)-Frequency loose stools-BD severity. VAT-FI offers an accurate means for characterizing BD, minimizing the need for extensive clinical data.
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Affiliation(s)
- Xuehua Li
- Department of Radiology, The First Affiliated Hospital, Sun Yat-Sen University, 58 Zhongshan II Road, Guangzhou 510080, People's Republic of China
| | - Cicong Hu
- Department of Radiology, The First Affiliated Hospital, Sun Yat-Sen University, 58 Zhongshan II Road, Guangzhou 510080, People's Republic of China
- Department of Radiology, The First Affiliated Hospital of Wenzhou Medical University, Nanbaixiang, Ouhai District, Wenzhou 325000, People's Republic of China
| | - Haipeng Wang
- Medical AI Lab, School of Biomedical Engineering, Medical School, Shenzhen University, Block A2, Lihu Campus of Shenzhen University, 1066 Xueyuan Avenue, Shenzhen 518000, People's Republic of China
| | - Yuqin Lin
- Department of Radiology, The First Affiliated Hospital of Shantou University Medical College, 57 Changping Road, Shantou 515000, People's Republic of China
| | - Jiaqiang Li
- Department of Radiology, The First People's Hospital of Foshan, No.81, Lingnan Dadao north, Foshan 528000, People's Republic of China
| | - Enming Cui
- Department of Radiology, Jiangmen Central Hospital, Guangdong Medical University, 23 Beijie Haibang Street, Jiangmen 529030, People's Republic of China
| | - Xiaozhao Zhuang
- Department of Radiology, Hainan General Hospital (Hainan Affiliated Hospital of Hainan Medical University), No.19 Xiuhua Road, Xiuying District, Haikou 570311, People's Republic of China
| | - Jianpeng Li
- Department of Radiology, Affiliated Dongguan People's Hospital, Southern Medical University, No. 78 Wandao Road, Dongguan 523000, People's Republic of China
| | - Jiahang Lu
- Medical Imaging Department, The First Affiliated Hospital, Kunming Medical University, Xi Chang Road 295th, Kunming 650000, People's Republic of China
| | - Ruonan Zhang
- Department of Radiology, The First Affiliated Hospital, Sun Yat-Sen University, 58 Zhongshan II Road, Guangzhou 510080, People's Republic of China
| | - Yangdi Wang
- Department of Radiology, The First Affiliated Hospital, Sun Yat-Sen University, 58 Zhongshan II Road, Guangzhou 510080, People's Republic of China
| | - Zhenpeng Peng
- Department of Radiology, The First Affiliated Hospital, Sun Yat-Sen University, 58 Zhongshan II Road, Guangzhou 510080, People's Republic of China
| | - Canhui Sun
- Department of Radiology, The First Affiliated Hospital, Sun Yat-Sen University, 58 Zhongshan II Road, Guangzhou 510080, People's Republic of China
| | - Ziping Li
- Department of Radiology, The First Affiliated Hospital, Sun Yat-Sen University, 58 Zhongshan II Road, Guangzhou 510080, People's Republic of China
| | - Minhu Chen
- Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-Sen University, 58 Zhongshan II Road, Guangzhou 510080, People's Republic of China
| | - Li Shi
- Department of Radiology, The Third Affiliated Hospital of Guangzhou Medical University, 63 Duobao Road, Guangzhou 510150, People's Republic of China
| | - Ren Mao
- Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-Sen University, 58 Zhongshan II Road, Guangzhou 510080, People's Republic of China
| | - Bingsheng Huang
- Medical AI Lab, School of Biomedical Engineering, Medical School, Shenzhen University, Block A2, Lihu Campus of Shenzhen University, 1066 Xueyuan Avenue, Shenzhen 518000, People's Republic of China
| | - Shi-Ting Feng
- Department of Radiology, The First Affiliated Hospital, Sun Yat-Sen University, 58 Zhongshan II Road, Guangzhou 510080, People's Republic of China
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Zhou M, Niu Z, Ma L, Li W, Xiao M, He Y, Qin J, Jiang Y, Liu W, Zhu Q. Detecting and characterizing creeping fat in Crohn's disease: agreement between intestinal ultrasound and computed tomography enterography. Insights Imaging 2024; 15:229. [PMID: 39312060 PMCID: PMC11420403 DOI: 10.1186/s13244-024-01807-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2024] [Accepted: 09/01/2024] [Indexed: 09/26/2024] Open
Abstract
OBJECTIVES Creeping fat (CF) is associated with stricture formation in Crohn's disease (CD). This study evaluated the feasibility of intestinal ultrasound (IUS) for semiquantitative analysis of CF and compared the agreement between IUS and computed tomography enterography (CTE). METHODS In this retrospective study, we recruited consecutive CD patients who underwent IUS and CTE. CF wrapping angle was analyzed on the most affected bowel segment and was independently evaluated by IUS and CTE. We evaluated the wrapping angle of CF in the cross- and vertical sections of the diseased bowel. CF wrapping angle was divided into < 180° and ≥ 180°. IUS performance was assessed using CTE as a reference standard, and IUS interobserver consistency was evaluated. RESULTS We enrolled 96 patients. CTE showed that CF wrapping angle was < 180° in 35 patients and ≥ 180° in 61 patients. We excluded three cases in which the observation positions were inconsistent between the IUS and CTE. Excellent agreement was shown between US and CTE (82/93, 88.2%). The eleven remaining cases showed inconsistencies mostly in the terminal ileum (n = 5) and small intestine (n = 4). Total agreement between IUS observers was 89.6% (86/96, κ = 0.839, p = 0.000), with perfect agreement for the ileocecal and colonic segments (35/37, 94.6% and 20/21, 95.2%, respectively) and moderate agreement for small intestinal segments (16/21, 76.2%). CONCLUSIONS IUS could be of value and complementary to CTE for assessing CF, particularly in patients with affected terminal ileum and colon. IUS is a non-invasive technique for monitoring CD patients. CRITICAL RELEVANCE STATEMENT In our study, excellent agreement was shown between intestinal US observers as well as between US and CT enterography (CTE) for assessing creeping fat (CF), which showed that ultrasound could be of value and complementary to CTE. KEY POINTS Creeping fat (CF) is a potential therapeutic target in Crohn's disease. Excellent agreement was shown between US and CT Enterography (CTE) for assessing CF. Ultrasound could be complementary to CTE for assessing CF.
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Affiliation(s)
- Mengyuan Zhou
- Department of Ultrasound, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 100730, Beijing, China
| | - Zihan Niu
- Department of Ultrasound, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 100730, Beijing, China
| | - Li Ma
- Department of Ultrasound, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 100730, Beijing, China
| | - Wenbo Li
- Department of Ultrasound, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 100730, Beijing, China
| | - Mengsu Xiao
- Department of Ultrasound, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 100730, Beijing, China
| | - Yudi He
- Department of Ultrasound, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 100730, Beijing, China
| | - Jing Qin
- Department of Ultrasound, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 100730, Beijing, China
| | - Yuxin Jiang
- Department of Ultrasound, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 100730, Beijing, China
| | - Wei Liu
- Department of Radiology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 100730, Beijing, China.
| | - Qingli Zhu
- Department of Ultrasound, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 100730, Beijing, China.
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Bak MTJ, Demers K, Hammoudi N, Allez M, Silverberg MS, Fuhler GM, Parikh K, Pierik MJ, Stassen LPS, van der Woude CJ, Doukas M, van Ruler O, de Vries AC. Systematic review: Patient-related, microbial, surgical, and histopathological risk factors for endoscopic post-operative recurrence in patients with Crohn's disease. Aliment Pharmacol Ther 2024; 60:310-326. [PMID: 38887827 DOI: 10.1111/apt.18040] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/29/2024] [Revised: 03/20/2024] [Accepted: 04/30/2024] [Indexed: 06/20/2024]
Abstract
BACKGROUND Risk stratification for endoscopic post-operative recurrence (ePOR) in Crohn's disease (CD) is required to identify patients who would benefit most from initiation of prophylactic medication and intensive monitoring of recurrence. AIMS To assess the current evidence on patient-related, microbial, surgical and histopathological risk factors for ePOR in patients with CD after ileocolic (re-)resection. METHODS Multiple online databases (Embase, MEDLINE, Web of Science and Cochrane Library) were searched up to March 2024. Studies with reported associations of patient-related, microbial, surgical and/or histopathological factors for ePOR (i.e., Rutgeerts' score ≥i2 or modified Rutgeerts' score ≥i2a) were included. The risk of bias was assessed with the Newcastle-Ottawa Scale for observational cohort studies and case-control studies. RESULTS In total, 47 studies were included (four RCTs, 29 cohort studies, 12 case-control studies, one cross-sectional study and one individual participant data meta-analysis) including 6006 patients (median sample size 87 patients [interquartile range 46-170]). Risk of bias assessment revealed a poor quality in 41% of the studies. An association was reported in multiple studies of ePOR with active smoking at and post-surgery, male sex and prior bowel resection. A heterogeneous association with ePOR was reported for other risk factors included in the current guidelines (penetrating disease, perianal disease, younger age, extensive small bowel disease and presence of granulomas in the resection specimen or myenteric plexitis in the resection margin), and other patient-related, microbial, surgical and histopathological factors. CONCLUSION Risk factors for ePOR in international guidelines are not consistently reported as risk factors in current literature except for active smoking and prior bowel resection. To develop evidence-based, personalised strategies, large prospective studies are warranted to identify risk factors for ePOR. Validation studies of promising (bio)markers are also required.
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Affiliation(s)
- Michiel T J Bak
- Department of Gastroenterology and Hepatology, Erasmus University Medical Center Rotterdam, Rotterdam, the Netherlands
| | - Karlijn Demers
- Research Institute for Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University, Maastricht, the Netherlands
- Department of Gastroenterology and Hepatology, Maastricht University Medical Center+, Maastricht, the Netherlands
- Department of Surgery, Maastricht University Medical Center+, Maastricht, the Netherlands
| | - Nassim Hammoudi
- Gastroenterology Department, Hôpital Saint-Louis - APHP, Université Paris Cité, INSERM U1160, Paris, France
| | - Matthieu Allez
- Gastroenterology Department, Hôpital Saint-Louis - APHP, Université Paris Cité, INSERM U1160, Paris, France
| | - Mark S Silverberg
- Inflammatory Bowel Disease Centre, Mount Sinai Hospital, Toronto, Ontario, Canada
| | - Gwenny M Fuhler
- Department of Gastroenterology and Hepatology, Erasmus University Medical Center Rotterdam, Rotterdam, the Netherlands
| | - Kaushal Parikh
- Department of Gastroenterology and Hepatology, Erasmus University Medical Center Rotterdam, Rotterdam, the Netherlands
| | - Marieke J Pierik
- Research Institute for Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University, Maastricht, the Netherlands
- Department of Gastroenterology and Hepatology, Maastricht University Medical Center+, Maastricht, the Netherlands
| | - Laurents P S Stassen
- Research Institute for Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University, Maastricht, the Netherlands
- Department of Surgery, Maastricht University Medical Center+, Maastricht, the Netherlands
| | - C Janneke van der Woude
- Department of Gastroenterology and Hepatology, Erasmus University Medical Center Rotterdam, Rotterdam, the Netherlands
| | - Michail Doukas
- Department of Pathology, Erasmus University Medical Center Rotterdam, Rotterdam, the Netherlands
| | - Oddeke van Ruler
- Department of Surgery, IJsselland Hospital, Capelle aan den IJssel, the Netherlands
- Department of Surgery, Erasmus University Medical Center Rotterdam, Rotterdam, the Netherlands
| | - Annemarie C de Vries
- Department of Gastroenterology and Hepatology, Erasmus University Medical Center Rotterdam, Rotterdam, the Netherlands
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Xiong Z, Wu P, Zhang Y, Chen J, Shen Y, Kamel I, Wu B, Zheng X, Li Z. Radiological biomarkers reflecting visceral fat distribution help distinguish inflammatory bowel disease subtypes: a multicenter cross-sectional study. Insights Imaging 2024; 15:70. [PMID: 38472526 DOI: 10.1186/s13244-024-01640-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2023] [Accepted: 02/09/2024] [Indexed: 03/14/2024] Open
Abstract
OBJECTIVES To achieve automated quantification of visceral adipose tissue (VAT) distribution in CT images and screen out parameters with discriminative value for inflammatory bowel disease (IBD) subtypes. METHODS This retrospective multicenter study included Crohn's disease (CD) and ulcerative colitis (UC) patients from three institutions between 2012 and 2021, with patients with acute appendicitis as controls. An automatic VAT segmentation algorithm was developed using abdominal CT scans. The VAT volume, as well as the coefficient of variation (CV) of areas within the lumbar region, was calculated. Binary logistic regression and receiver operating characteristic analysis was performed to evaluate the potential of indicators to distinguish between IBD subtypes. RESULTS The study included 772 patients (365 CDs, median age [inter-quartile range] = 31.0. (25.0, 42.0) years, 255 males; 241 UCs, 46.0 (34.0, 55.5) years, 138 males; 166 controls, 40.0 (29.0, 53.0) years, 80 males). CD patients had lower VAT volume (CD = 1584.95 ± 1128.31 cm3, UC = 1855.30 ± 1326.12 cm3, controls = 2470.91 ± 1646.42 cm3) but a higher CV (CD = 29.42 ± 15.54 %, p = 0.006 and p ˂ 0.001) compared to UC and controls (25.69 ± 12.61 % vs. 23.42 ± 15.62 %, p = 0.11). Multivariate analysis showed CV was a significant predictor for CD (odds ratio = 6.05 (1.17, 31.12), p = 0.03). The inclusion of CV improved diagnostic efficiency (AUC = 0.811 (0.774, 0.844) vs. 0.803 (0.766, 0.836), p = 0.08). CONCLUSION CT-based VAT distribution can serve as a potential biomarker for distinguishing IBD subtypes. CRITICAL RELEVANCE STATEMENT Visceral fat distribution features extracted from CT images using an automated segmentation algorithm (1.14 min) show differences between Crohn's disease and ulcerative colitis and are promising for practical radiological screening. KEY POINTS • Radiological parameters reflecting visceral fat distribution were extracted for the discrimination of Crohn's disease (CD) and ulcerative colitis (UC). • In CD, visceral fat was concentrated in the lower lumbar vertebrae, and the coefficient of variation was a significant predictor (OR = 6.05 (1.17, 31.12), p = 0.03). • The differences between CD, UC, and controls are promising for practical radiological screening.
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Affiliation(s)
- Ziman Xiong
- Department of Radiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Qiaokou District, Wuhan, 430030, Hubei, China
| | - Peili Wu
- Department of Radiology, The First Affiliated Hospital of Fujian Medical University, Fuzhou, 350005, Fujian, China
| | - Yan Zhang
- Department of Radiology, West China Hospital, Sichuan University, No. 37, Guoxue Alley, Chengdu, 610041, Sichuan, China
| | - Jun Chen
- GE Healthcare, Wuhan, 430030, Hubei, China
| | - Yaqi Shen
- Department of Radiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Qiaokou District, Wuhan, 430030, Hubei, China.
| | - Ihab Kamel
- Department of Radiology, University of Colorado Denver Anschutz Medical Campus, Aurora, MD, 80045, USA
| | - Bing Wu
- Department of Radiology, West China Hospital, Sichuan University, No. 37, Guoxue Alley, Chengdu, 610041, Sichuan, China.
| | - Xianying Zheng
- Department of Radiology, Fujian Maternity and Child Health Hospital, Fuzhou, 350005, Fujian, China.
| | - Zhen Li
- Department of Radiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Qiaokou District, Wuhan, 430030, Hubei, China
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Tuma ISM, Cambi MPC, Moraes TPD, Magro DO, Kotze PG. BODY FAT COMPOSITION IN PATIENTS WITH INFLAMMATORY BOWEL DISEASES: A COMPARATIVE STUDY BETWEEN SKINFOLDS AND ULTRASONOGRAPHY. ARQUIVOS DE GASTROENTEROLOGIA 2024; 61:e23088. [PMID: 38451660 DOI: 10.1590/s0004-2803.246102023-88] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/13/2023] [Accepted: 10/23/2023] [Indexed: 03/08/2024]
Abstract
BACKGROUND Inflammatory bowel diseases (IBD) are associated with important changes in nutritional status. OBJECTIVE The aim of the study was to compare body fat composition between two anthropometric methods: skinfolds and ultrasonography, in patients with IBD. METHODS Single-center cross-sectional study with IBD patients in remission or active disease. For the agreement analysis between the body fat assessment methods, the Bland Altman method was used. RESULTS A total of 101 patients with IBD were included, 75 with Crohn's disease and 26 with ulcerative colitis. Approximately 56% of the patients with Crohn's disease and 65.4% of those with ulcerative colitis had a body fat composition above normal levels, with no significant difference between the diseases (P=0.63). The Bland-Altman concordance analysis showed that the methods for assessing the percentage of fat by the adipometer and ultrasound were not in full agreement (P=0.001), despite both presented good correlation (CC 0.961; P=0.000). CONCLUSION The analysis of body fat percentage in patients with IBD was different between the skinfolds and ultrasound. Both methods can be used to assess the of body fat percentage of patients with IBD. However, monitoring of body fat sequentially and longitudinally should always be performed using the same method throughout the disease course. Prospective longitudinal studies are warranted to precisely define the role of these two methods of measuring body composition in patients with IBD. BACKGROUND • Inflammatory bowel diseases are associated with changes in nutritional status. BACKGROUND • Skinfolds measurements and ultrasound are valid methods for assessing body composition and body fat. BACKGROUND • These methods despite comparable are not identical and are useful in clinical nutritional practices in IBD.
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Affiliation(s)
- Isadora Sayuri Macedo Tuma
- Pontifícia Universidade Católica do Paraná, Unidade de Cirurgia Colorretal, Ambulatório de DII, Curitiba, PR, Brasil
| | - Maria Paula Carlin Cambi
- Pontifícia Universidade Católica do Paraná, Unidade de Cirurgia Colorretal, Ambulatório de DII, Curitiba, PR, Brasil
| | - Thyago Proença de Moraes
- Pontifícia Universidade Católica do Paraná, Unidade de Cirurgia Colorretal, Ambulatório de DII, Curitiba, PR, Brasil
| | - Daniéla Oliveira Magro
- Faculdade de Ciências Médicas da Universidade Estadual de Campinas, Departamento de Cirurgia, Campinas, SP, Brasil
| | - Paulo Gustavo Kotze
- Pontifícia Universidade Católica do Paraná, Unidade de Cirurgia Colorretal, Ambulatório de DII, Curitiba, PR, Brasil
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Li X, Wu W, Yuan Y, Zhu Z, Liu X, Xiao D, Long X. CT energy spectral parameters of creeping fat in Crohn's disease and correlation with inflammatory activity. Insights Imaging 2024; 15:10. [PMID: 38228821 DOI: 10.1186/s13244-023-01592-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2023] [Accepted: 12/09/2023] [Indexed: 01/18/2024] Open
Abstract
OBJECTIVES Creeping fat is a kind of unique abnormal mesenteric tissue at the sites of diseased bowel of Crohn's disease. By using dual-energy CT enterography, this study aimed to evaluate the feasibility of spectral parameters in the quantitative analysis of mesenteric adipose tissue or creeping fat. METHODS In this study, patients with known or suspected Crohn's disease who underwent dual-energy CT enterography from March 1, 2019, to March 31, 2021, were enrolled. Among them, 40 patients with surgery and pathology-proven creeping fat were selected as the creeping fat Crohn's disease group, and 40 normal patients were selected as the control group. The quantitative spectral parameters including the slope of the Hounsfield unit curve, normalised fat-water concentration, normalised fat-iodine concentration, and normalised fat volume fraction at the enteric phases were obtained. Mann-Whitney U test, Kruskal-Wallis H test, and receiver operating characteristic curve analysis were applied to compare quantitative parameters among various groups. RESULTS A significant difference was observed in the slope of the Hounsfield unit curve, normalised fat-water concentration, normalised fat-iodine concentration, and normalised fat volume fraction between mesenteric adipose tissue and creeping fat with Crohn's disease at the enteric phase (all p < 0.001). The slope of the Hounsfield unit curve of creeping fat at the enteric phase had a better capability to distinguish inactive and active Crohn's disease (AUC = 0.93, p < 0.001). CONCLUSION Dual-energy CT enterography with quantitative spectral parameters is a potentially novel noninvasive tool for evaluating creeping fat in Crohn's disease. CRITICAL RELEVANCE STATEMENT Energy spectral parameters of creeping fat in Crohn's disease are significantly different from normal mesenteric adipose tissues and are correlated with inflammatory activity. KEY POINTS • Dual-energy CT enterography allows quantitatively assessing creeping fat with spectral parameters. • The creeping fat has distinct spectral parameters to normal mesenteric adipose. • The spectral parameters accurately differentiate active and inactive Crohn's disease.
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Affiliation(s)
- Xianchu Li
- Department of Radiology, The Second Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, China
- Department of Radiology, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, 410008, China
| | - Wei Wu
- Department of General Surgery, Xiangya Hospital, Central South University, Changsha, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China
| | - Yan Yuan
- Department of Radiology, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, 410008, China
| | - Zhiming Zhu
- Department of Radiology, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, 410008, China
| | - Xiaowei Liu
- Department of Gastroenterology, Xiangya Hospital, Central South University, Changsha, China
| | - Desheng Xiao
- Department of Pathology, Xiangya Hospital, Central South University, Changsha, China
| | - Xueying Long
- Department of Radiology, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, 410008, China.
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China.
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9
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Li Y, Xiong Z, Jiang Y, Shen Y, Hu X, Hu D, Li Z. Enhancing the Differentiation between Intestinal Behçet's Disease and Crohn's Disease through Quantitative Computed Tomography Analysis. Bioengineering (Basel) 2023; 10:1211. [PMID: 37892941 PMCID: PMC10604024 DOI: 10.3390/bioengineering10101211] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2023] [Revised: 10/13/2023] [Accepted: 10/13/2023] [Indexed: 10/29/2023] Open
Abstract
Behçet's disease (BD) behaves similarly to Crohn's disease (CD) when the bowel is involved. Computed tomography enterography (CTE) can accurately show intestinal involvement and obtain body composition data. The objective of this study was to evaluate whether CTE could improve the ability to distinguish between intestinal BD and CD. This study evaluated clinical, laboratory, endoscopic, and CTE features on first admission. Body composition analysis was based on the CTE arterial phase. The middle layers of the L1-L5 vertebral body were selected. The indicators assessed included: the area ratio of visceral adipose tissue (VAT)/subcutaneous adipose tissue (SAT) (VSR) in each layer, the total volume ratio of VAT/SAT, the quartile of VAT attenuation in each layer and the coefficient of variation (CV) of the VAT area for each patient was also calculated. Two models were developed based on the above indicators: one was a traditional model (age, gender, ulcer distribution) and the other was a comprehensive model (age, gender, ulcer distribution, proximal ileum involvement, asymmetrical thickening of bowel wall, intestinal stenosis, VSRL4, and CV). The areas under the receiver operating characteristic (ROC) curve of the traditional (sensitivity: 80.0%, specificity: 81.0%) and comprehensive (sensitivity: 95.0%, specificity: 87.2%) models were 0.862 and 0.941, respectively (p = 0.005).
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Affiliation(s)
| | | | | | - Yaqi Shen
- Department of Radiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China; (Y.L.); (Z.X.); (Y.J.); (X.H.); (D.H.); (Z.L.)
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10
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Weidinger C, Siegmund B. Deciphering Cellular Networks in Creeping Fat. Inflamm Bowel Dis 2023; 29:1670-1672. [PMID: 36916523 DOI: 10.1093/ibd/izad046] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/22/2022] [Indexed: 03/16/2023]
Affiliation(s)
- Carl Weidinger
- From the Division of Gastroenterology, Infectiology and Rheumatology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
| | - Britta Siegmund
- From the Division of Gastroenterology, Infectiology and Rheumatology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
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11
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van Schelt AS, Beek KJ, Wassenaar NPM, Schrauben EM, Runge JH, Gecse KB, van der Bilt JDW, Neefjes-Borst EA, Buskens CJ, Nederveen AJ, Stoker J. Viscoelastic properties of small bowel mesentery at MR elastography in Crohn's disease: a prospective cross-sectional exploratory study. Eur Radiol Exp 2023; 7:53. [PMID: 37718360 PMCID: PMC10505604 DOI: 10.1186/s41747-023-00366-5] [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: 04/13/2023] [Accepted: 06/22/2023] [Indexed: 09/19/2023] Open
Abstract
BACKGROUND Creeping fat is a pathological feature of small bowel Crohn's disease (CD), with literature suggesting that bowel resection with extended mesenteric resection is related to less postoperative recurrences. Conventional imaging is unable to accurately quantify the disease involvement (i.e., fibrosis) of creeping fat. Quantification of disease involvement could be useful in decision-making for additional extended mesenteric resection. We investigated the feasibility of magnetic resonance elastography (MRE) of the mesentery and if MRE is capable to detect fibrotic disease involvement of mesentery in active CD. METHODS Multifrequency MRE yielded spatial stiffness (shear wave speed, SWS, |G*|) and fluidity maps (φ). Viscoelastic properties of seven CD patients' mesentery were compared to age- and sex-matched healthy volunteers (HV) (Mann-Whitney U-test). Within CD patients, the affected and "presumably" unaffected mesentery were compared (Wilcoxon-signed rank test). Repeatability was tested in 15 HVs (Bland-Altman analysis, coefficient of variation [CoV]). Spearman rank correlations were used to investigate the relation between microscopically scored amount of mesenteric fibrosis and viscoelastic parameters. RESULTS SWS, |G*|, and φ of affected mesentery in CD were higher compared to HV (p = 0.017, p = 0.001, p = 0.017). Strong correlations were found between percentage of area of mesenteric fibrosis and SWS and |G*| (p < 0.010). No differences were found within CD between affected and presumably unaffected mesentery. Repeatability of SWS showed 95% limits of agreement of (-0.09, 0.13 m/s) and within-subject CoV of 5.3%. CONCLUSION MRE may have the potential to measure fibrotic disease involvement of the mesentery in CD, possibly guiding clinical decision-making with respect to extended mesenteric resection. TRIAL REGISTRATION Dutch trial register, NL9105 , registered 7 December 2020. RELEVANCE STATEMENT MRE may have the potential to measure the amount of mesenteric fibrosis of the affected mesenteric fat in active Crohn's disease, giving more insight into disease progression and could potentially play a role in clinical decision-making for extended mesenteric resection. KEY POINTS • MRE of the mesentery in patients with active CD is feasible. • Fluidity and stiffness of the mesentery increase in active CD, while stiffness correlates with the histopathological amount of mesenteric fibrosis. • MRE provides biomarkers to quantify mesenteric disease activity in active CD.
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Affiliation(s)
- Anne-Sophie van Schelt
- Department of Radiology and Nuclear Medicine, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
- Cancer Center Amsterdam, Imaging and Biomarkers, Amsterdam, The Netherlands
| | - Kim Johanna Beek
- Department of Radiology and Nuclear Medicine, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.
- Amsterdam Gastroenterology, Endocrinology, Metabolism, Amsterdam, The Netherlands.
| | - Nienke Petronella Maria Wassenaar
- Department of Radiology and Nuclear Medicine, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
- Cancer Center Amsterdam, Imaging and Biomarkers, Amsterdam, The Netherlands
| | - Eric M Schrauben
- Department of Radiology and Nuclear Medicine, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
| | - Jurgen H Runge
- Department of Radiology and Nuclear Medicine, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
- Department of Radiology, Netherlands Cancer Institute, Amsterdam, The Netherlands
| | - Krisztina Barbara Gecse
- Amsterdam Gastroenterology, Endocrinology, Metabolism, Amsterdam, The Netherlands
- Department of Gastroenterology and Hepatology, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
| | - Jarmila D W van der Bilt
- Amsterdam Gastroenterology, Endocrinology, Metabolism, Amsterdam, The Netherlands
- Department of Surgery, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
| | - E Andra Neefjes-Borst
- Amsterdam Gastroenterology, Endocrinology, Metabolism, Amsterdam, The Netherlands
- Department of Pathology, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
| | - Christianne Johanna Buskens
- Amsterdam Gastroenterology, Endocrinology, Metabolism, Amsterdam, The Netherlands
- Department of Surgery, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
| | - Aart J Nederveen
- Department of Radiology and Nuclear Medicine, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
| | - Jaap Stoker
- Department of Radiology and Nuclear Medicine, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
- Cancer Center Amsterdam, Imaging and Biomarkers, Amsterdam, The Netherlands
- Amsterdam Gastroenterology, Endocrinology, Metabolism, Amsterdam, The Netherlands
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12
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Tang W, Xie G, Li J, Tan W, Yi R, Yang L, Zhang L, Deng J, Zhang Y, Li K. Body composition parameters correlate with the endoscopic severity in Crohn's disease patients treated with infliximab. Front Nutr 2023; 10:1251448. [PMID: 37674885 PMCID: PMC10478258 DOI: 10.3389/fnut.2023.1251448] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2023] [Accepted: 08/07/2023] [Indexed: 09/08/2023] Open
Abstract
Background The disease activity status and behavior of Crohn's disease (CD) can reflect the severity of the disease, and changes in body composition are common in CD patients. Aims The aim of this study was to investigate the relationship between body composition parameters and disease severity in CD patients treated with infliximab (IFX). Methods Patients with CD assessed with the simple endoscopic score (SES-CD) and were treated with IFX were retrospectively collected, and body composition parameters at the level of the 3rd lumbar vertebrae were calculated from computed tomography (CT) scans of the patients. The correlation of patients' body composition parameters with disease activity status and disease behavior was analyzed, and the diagnostic value of the relevant parameters was assessed using receiver operating characteristic (ROC) curves. Results A total of 106 patients were included in this study. There were significant differences in the subcutaneous adiposity index (SAI) (p = 0.010), the visceral adiposity index (VAI) (p < 0.001), the skeletal muscle mass index (SMI) (p < 0.001), and decreased skeletal muscle mass (p < 0.001) among patients with different activity status. After Spearman and multivariate regression analysis, SAI (p = 0.006 and p = 0.001), VAI (p < 0.001 and p < 0.001), and SMI (p < 0.001and p = 0.007) were identified as independent correlates of disease activity status (both disease activity and moderate-to-severe activity), with disease activity status independently positively correlated with SAI and SMI and independently negatively correlated with VAI. In determining the disease activity and moderate-to-severe activity status, SMI performed best relative to SAI and VAI, with areas under the ROC curve of 0.865 and 0.801, respectively. SAI (p = 0.015), SMI (p = 0.011) and decreased skeletal muscle mass (p = 0.027) were significantly different between different disease behavior groups (inflammatory disease behavior group, complex disease behavior group) but were not independent correlates (p > 0.05). Conclusion Body composition parameters of CD patients treated with IFX correlate with the endoscopic disease severity, and SMI can be used as a reliable indicator of disease activity status.
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Affiliation(s)
- Wuli Tang
- Chongqing Medical University, Chongqing, China
- Chongqing Institute of Green and Intelligent Technology, Chinese Academy of Sciences, Chongqing, China
- Chongqing School, University of Chinese Academy of Science, Chongqing, China
- Department of Radiology, Chongqing General Hospital, Chongqing, China
| | - Gang Xie
- Department of Radiology, The Third People’s Hospital of Chengdu, Chengdu, China
| | - Junlin Li
- Department of Radiology, Chongqing General Hospital, Chongqing, China
| | - Wei Tan
- Department of Gastroenterology, Chongqing General Hospital, Chongqing, China
| | - Rongqi Yi
- Department of Radiology, Chongqing General Hospital, Chongqing, China
| | - Ling Yang
- Department of Radiology, Chongqing General Hospital, Chongqing, China
| | - Lingqin Zhang
- Department of Radiology, Chongqing General Hospital, Chongqing, China
| | - Jiaxing Deng
- Department of General Medicine, Chongqing General Hospital, Chongqing, China
| | - Yue Zhang
- Department of Radiology, Chongqing General Hospital, Chongqing, China
| | - Kang Li
- Chongqing Medical University, Chongqing, China
- Chongqing Institute of Green and Intelligent Technology, Chinese Academy of Sciences, Chongqing, China
- Chongqing School, University of Chinese Academy of Science, Chongqing, China
- Department of Radiology, Chongqing General Hospital, Chongqing, China
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Surdea-Blaga T, Ismaiel A, Jaaouani A, Leucuta DC, Elsayed A, Ismaiel M, Ben Ameur I, Al Srouji N, Popa SL, Grad S, Ensar D, Dumitrascu DL. Adiponectin Levels in Inflammatory Bowel Disease: A Systematic Review and Meta-Analysis. Dig Dis 2023; 41:860-871. [PMID: 37385235 DOI: 10.1159/000531614] [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: 01/23/2023] [Accepted: 06/12/2023] [Indexed: 07/01/2023]
Abstract
INTRODUCTION Adipose tissue plays an important role in the pathogenesis of inflammatory conditions. The role of adipokines in inflammatory bowel disease (IBD) has been evaluated in the current literature with conflicting results. The aim of this study was to evaluate adiponectin levels in IBD patients, including Crohn's disease (CD) and ulcerative colitis (UC), compared to controls, as well as further subgroup analyses. Hence, assessing the potential role of adiponectin as a surrogate marker. METHODS We performed a systematic electronic search on PubMed, Embase, Scopus, and Cochrane Library, including observational or interventional studies evaluating serum or plasma adiponectin levels in IBD patients in humans. The primary summary outcome was the mean difference (MD) in serum or plasma adiponectin levels between IBD patients versus controls. Subgroup analyses were conducted involving adiponectin levels in CD and UC compared to controls, as well as CD compared to UC. RESULTS A total of 20 studies were included in our qualitative synthesis and 14 studies in our quantitative synthesis, with a total population sample of 2,085 subjects. No significant MD in serum adiponectin levels was observed between IBD patients versus controls {-1.331 (95% confidence interval [CI]: -3.135-0.472)}, UC patients versus controls (-0.213 [95% CI: -1.898-1.472]), and CD patients versus controls (-0.851 [95% CI: -2.263-0.561]). Nevertheless, a significant MD was found between UC patients versus CD patients (0.859 [95% CI: 0.097-1.622]). CONCLUSIONS Serum adiponectin levels were not able to differentiate between IBD, UC, and CD patients compared to controls. However, significantly higher serum adiponectin levels were observed in UC compared to CD patients.
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Affiliation(s)
- Teodora Surdea-Blaga
- 2nd Department of Internal Medicine, "Iuliu Hatieganu" University of Medicine and Pharmacy, Cluj-Napoca, Romania
| | - Abdulrahman Ismaiel
- 2nd Department of Internal Medicine, "Iuliu Hatieganu" University of Medicine and Pharmacy, Cluj-Napoca, Romania
| | - Ayman Jaaouani
- Faculty of Medicine, "Iuliu Hatieganu" University of Medicine and Pharmacy, Cluj-Napoca, Romania
| | - Daniel-Corneliu Leucuta
- Department of Medical Informatics and Biostatistics, "Iuliu Hatieganu" University of Medicine and Pharmacy, Cluj-Napoca, Romania
| | - Abdalla Elsayed
- Department of Internal Medicine, County Emergency Hospital Ilfov, Bucharest, Romania
| | - Mohamed Ismaiel
- Department of General Surgery, Connolly Hospital Blanchardstown, Dublin, Ireland
| | - Inès Ben Ameur
- Faculty of Medicine, "Iuliu Hatieganu" University of Medicine and Pharmacy, Cluj-Napoca, Romania
| | - Nahlah Al Srouji
- 2nd Department of Internal Medicine, "Iuliu Hatieganu" University of Medicine and Pharmacy, Cluj-Napoca, Romania
| | - Stefan-Lucian Popa
- 2nd Department of Internal Medicine, "Iuliu Hatieganu" University of Medicine and Pharmacy, Cluj-Napoca, Romania
| | - Simona Grad
- 2nd Department of Internal Medicine, "Iuliu Hatieganu" University of Medicine and Pharmacy, Cluj-Napoca, Romania
| | - Dilara Ensar
- Department of Medicine, Tallaght University Hospital, Dublin, Ireland
| | - Dan L Dumitrascu
- 2nd Department of Internal Medicine, "Iuliu Hatieganu" University of Medicine and Pharmacy, Cluj-Napoca, Romania
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Aggeletopoulou I, Tsounis EP, Mouzaki A, Triantos C. Creeping Fat in Crohn's Disease-Surgical, Histological, and Radiological Approaches. J Pers Med 2023; 13:1029. [PMID: 37511642 PMCID: PMC10381426 DOI: 10.3390/jpm13071029] [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: 05/23/2023] [Revised: 06/16/2023] [Accepted: 06/19/2023] [Indexed: 07/30/2023] Open
Abstract
During the course of Crohn's disease, the response of mesenteric adipose tissue to the production of inflammatory mediators and bacterial invasion through the intestinal mucosa results in the formation of creeping fat. Creeping fat describes the arresting finger-like projections that surround the inflamed bowel. In this review, the microscopic and macroscopic features of creeping fat and histological evidence for the importance of this tissue are discussed. Moreover, the most recent insights into the radiological assessment of creeping fat in patients with Crohn's disease are reported. Advances in imaging techniques have revolutionized the possibility of visualization and quantification of adipose tissue depots with excellent accuracy. Visceral fat has been significantly correlated with various Crohn's-disease-related outcomes. Despite the difficulties in distinguishing physiologic perienteric fat from creeping fat, the growing interest in fat-wrapping in Crohn's disease has rejuvenated radiologic research. With regard to the noninvasive fat-wrapping assessment, a novel CT enterography-based mesenteric creeping fat index has been developed for the mitigation of the confounding effect of normal retroperitoneal and perienteric adipose tissue. Research on machine learning algorithms and computational radiomics in conjunction with mechanistic studies may be the key for the elucidation of the complex role of creeping fat in Crohn's disease.
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Affiliation(s)
- Ioanna Aggeletopoulou
- Division of Gastroenterology, Department of Internal Medicine, University Hospital of Patras, 26504 Patras, Greece; (I.A.); (E.P.T.)
- Division of Hematology, Department of Internal Medicine, Medical School, University of Patras, 26504 Patras, Greece;
| | - Efthymios P. Tsounis
- Division of Gastroenterology, Department of Internal Medicine, University Hospital of Patras, 26504 Patras, Greece; (I.A.); (E.P.T.)
| | - Athanasia Mouzaki
- Division of Hematology, Department of Internal Medicine, Medical School, University of Patras, 26504 Patras, Greece;
| | - Christos Triantos
- Division of Gastroenterology, Department of Internal Medicine, University Hospital of Patras, 26504 Patras, Greece; (I.A.); (E.P.T.)
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15
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Tang W, Xie G, Wang D, Li T, Ren Y, Li J, Deng J, Li K. Imaging-based assessment of body composition in patients with Crohn's disease: a systematic review. Int J Colorectal Dis 2023; 38:126. [PMID: 37171498 DOI: 10.1007/s00384-023-04413-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 04/25/2023] [Indexed: 05/13/2023]
Abstract
BACKGROUND AND AIMS Body composition changes in patients with Crohn's disease (CD) have received increasing attention in recent years. This review aims to describe the changes in body composition in patients with CD on imaging and to analyze and summarize the prognostic value of body composition. METHODS We systematically searched Web of Science, PubMed, Embase, Cochrane Library, and Medline via OVID for literature published before November 2022, and two researchers independently evaluated the quality of the retrieved literature. RESULTS A total of 39 publications (32 cohort studies and 7 cross-sectional studies) involving 4219 patients with CD were retrieved. Imaging methods for body composition assessment, including dual-energy X-ray absorptiometry (DXA), computed tomography (CT) and magnetic resonance imaging (MRI), were included in this review. The study found that patients with CD typically have more visceral adipose tissue and less skeletal muscle mass, and the prevalence of sarcopenia and visceral obesity was significantly different in different studies (sarcopenia: 16-100%; visceral obesity: 5.3-30.5%). Available studies suggest that changes in the body composition of CD patients are significantly related to inflammatory status, disease behavior, poor outcomes, and drug efficacy. CONCLUSION Altered body composition can be a significant predictor of poor outcomes for CD patients. Therefore, the body composition of CD patients may serve as a potential therapeutic target to help optimize disease management strategies in clinical practice.
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Affiliation(s)
- Wuli Tang
- Chongqing Medical University, Chongqing, China
- Chongqing Institute of Green and Intelligent Technology, Chinese Academy of Sciences, Chongqing, China
- Chongqing School, University of Chinese Academy of Science, Chongqing, China
- Department of Radiology, Chongqing General Hospital, Chongqing, China
| | - Gang Xie
- Department of Radiology, Chongqing General Hospital, Chongqing, China
| | - Danni Wang
- Department of Radiology, Chongqing General Hospital, Chongqing, China
| | - Ting Li
- Department of Radiology, Chongqing General Hospital, Chongqing, China
| | - Yitao Ren
- Department of Radiology, Chongqing General Hospital, Chongqing, China
| | - Junlin Li
- Department of Radiology, Chongqing General Hospital, Chongqing, China
| | - Jiaxing Deng
- Department of Radiology, Chongqing General Hospital, Chongqing, China
| | - Kang Li
- Chongqing Medical University, Chongqing, China.
- Department of Radiology, Chongqing General Hospital, Chongqing, China.
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Barajas Ordonez F, Melekh B, Rodríguez-Feria P, Damm R, Thormann M, March C, Omari J, Pech M, Surov A. Parameters of body composition and creeping fat are associated with activity of Crohn's disease. Magn Reson Imaging 2023; 98:1-6. [PMID: 36634829 DOI: 10.1016/j.mri.2023.01.005] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2022] [Accepted: 01/06/2023] [Indexed: 01/11/2023]
Abstract
AIM This study aimed at assessing body composition parameters, creeping fat (CrF), and Crohn's disease's (CD) activity based on the Magnetic Resonance Index of Activity (MaRIA). METHODS 114 CD patients who underwent magnetic resonance enterography (MRE) between June 2010 and April 2020 were retrospectively assessed. The semi-automated body composition segmentation, the qualitative evaluation of CrF, and MaRIA were performed. Based on their MaRIA score, patients were divided into two groups: mild-to-moderate disease (MaRIA <11, n = 50) and severe disease (MaRIA ≥11, n = 64). MRE parameters were analyzed between both groups. Patients were dichotomized according to body composition categories and the presence of CrF. Univariate regression analyses were performed to investigate the association between dichotomized variables and severe disease. Significant variables were incorporated into the multivariate logistic regression model. RESULTS The severe disease group exhibited higher serum C-reactive protein (CRP) levels compared to the mild-to-moderate disease group (p ≤0.001). In the mild-to-moderate disease group, a higher proportion of patients had a body mass index (BMI) ≥ 25 (kg/m2) (32.0%) compared to the severe disease group (16.5%) (p = 0.04). The subcutaneous adipose tissue index (SATI) was significantly higher in the mild-to-moderate disease group (p = 0.04). The visceral to subcutaneous adipose tissue (VAT/SAT) ratio tended to be higher in the severe disease group (p = 0.09). There was no significant difference between both groups regarding total adipose tissue index (TATI) (p = 0.10), visceral adipose tissue index (VATI) (p = 0.51), intramuscular adipose tissue index (IMATI) (p = 0.38), skeletal muscle index (SMI) (p = 0.83), and sarcopenia (p = 0.75). In the multivariate analysis, CrF was significantly associated with severe disease (odds ratio [OR] 11.50, 95% confidence interval [CI] 3.13-42.17; p ≤0.001). Additionally, a BMI ≥ 25 (kg/m2) was protective against severe disease (OR: 0.34, 95% CI 0.12-0.95; p = 0.04). CONCLUSION CrF is significantly associated with CD activity.
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Affiliation(s)
- Felix Barajas Ordonez
- University Clinic for Radiology and Nuclear Medicine, University Hospital Magdeburg, Magdeburg, Germany.
| | - Bohdan Melekh
- University Clinic for Radiology and Nuclear Medicine, University Hospital Magdeburg, Magdeburg, Germany.
| | - Pablo Rodríguez-Feria
- Department of International Health, CAPHRI - Care and Public Health Research Institute, Maastricht University, the Netherlands.
| | - Robert Damm
- University Clinic for Radiology and Nuclear Medicine, University Hospital Magdeburg, Magdeburg, Germany.
| | - Maximilian Thormann
- University Clinic for Radiology and Nuclear Medicine, University Hospital Magdeburg, Magdeburg, Germany.
| | - Christine March
- University Clinic for Radiology and Nuclear Medicine, University Hospital Magdeburg, Magdeburg, Germany.
| | - Jazan Omari
- University Clinic for Radiology and Nuclear Medicine, University Hospital Magdeburg, Magdeburg, Germany.
| | - Maciej Pech
- University Clinic for Radiology and Nuclear Medicine, University Hospital Magdeburg, Magdeburg, Germany.
| | - Alexey Surov
- University Clinic for Radiology and Nuclear Medicine, University Hospital Magdeburg, Magdeburg, Germany.
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Jabłońska B, Mrowiec S. Nutritional Status and Its Detection in Patients with Inflammatory Bowel Diseases. Nutrients 2023; 15:1991. [PMID: 37111210 PMCID: PMC10143611 DOI: 10.3390/nu15081991] [Citation(s) in RCA: 31] [Impact Index Per Article: 15.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2023] [Revised: 04/15/2023] [Accepted: 04/19/2023] [Indexed: 04/29/2023] Open
Abstract
Malnutrition is an important issue in patients with inflammatory bowel diseases (IBDs) including Crohn's disease (CD) and ulcerative colitis (UC). It is caused by altered digestion and absorption within the small bowel, inadequate food intake, and drug-nutrient interactions in patients. Malnutrition is an essential problem because it is related to an increased risk of infections and poor prognosis in patients. It is known that malnutrition is also related to an increased risk of postsurgery complications in IBD patients. Basic nutritional screening involves anthropometric parameters with body mass index (BMI) and others (fat mass, waist-to-hip ratio, muscle strength), medical history concerning weight loss, and biochemical parameters (including the Prognostic Nutritional Index). Besides standard nutritional screening tools, including the Subjective Global Assessment (SGA), Nutritional Risk Score 2002 (NRS 2002), and Malnutrition Universal Screening Tool (MUST), specific nutritional screening tools are used in IBD patients, such as the Saskatchewan Inflammatory Bowel Disease-Nutrition Risk Tool (SaskIBD-NR Tool and IBD-specific Nutritional Screening Tool). There is a higher risk of nutrient deficiencies (including iron, zinc, magnesium) and vitamin deficiencies (including folic acid, vitamin B12 and D) in IBD patients. Therefore, regular evaluation of nutritional status is important in IBD patients because many of them are undernourished. An association between plasma ghrelin and leptin and nutritional status in IBD patients has been observed. According to some authors, anti-tumor necrosis factor (anti-TNFα) therapy (infliximab) can improve nutritional status in IBD patients. On the other hand, improvement in nutritional status may increase the response rate to infliximab therapy in CD patients. Optimization of nutritional parameters is necessary to improve results of conservative and surgical treatment and to prevent postoperative complications in patients with IBDs. This review presents basic nutritional screening tools, anthropometric and laboratory parameters, dietary risk factors for IBDs, common nutrient deficiencies, associations between anti-TNFα therapy and nutritional status, selected features regarding the influence of nutritional status, and surgical outcome in IBD patients.
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Affiliation(s)
- Beata Jabłońska
- Department of Digestive Tract Surgery, Medical University of Silesia, 40-752 Katowice, Poland
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18
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Khan N, Mahmud N, Patel M, Sundararajan R, Reinisch W. Risk of severe and opportunistic infections and the impact of SARS-COV-2 on this risk in a nationwide cohort of patients with inflammatory bowel disease. Aliment Pharmacol Ther 2023; 57:800-807. [PMID: 36645110 PMCID: PMC10023400 DOI: 10.1111/apt.17393] [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: 10/20/2022] [Revised: 11/27/2022] [Accepted: 01/04/2023] [Indexed: 01/17/2023]
Abstract
BACKGROUND The Inflammatory Bowel Disease (IBD) patients have adopted lifestyle modifications to prevent infection via SARS COV-2. AIMS This study aims to examine rate of serious infections and opportunistic infections in the pre-pandemic and pandemic period, and to analyse if the risk associated with medications used to treat IBD were potentially modified by associated change in lifestyle. METHODS We conducted a retrospective cohort study of patients from the US national Veteran Affairs Healthcare System (VAHS). Patients were stratified into two groups: pre-pandemic (prior to SARS COV-2 pandemic) and pandemic (during SARS COV-2 pandemic) and outcomes were measured in these groups. Primary outcome was occurrence of any serious infection. Secondary outcome was occurrence of any opportunistic infection. RESULTS There were 17,202 IBD patients in the pre-pandemic era and 15,903 patients in the pandemic era. The pre-pandemic era had a significantly higher proportion of serious infections relative to the pandemic era (5.1% vs. 4.4%, p = 0.002). The proportion of opportunistic infections were similar between pre-pandemic and pandemic eras (0.3% vs. 0.3%, p = 0.82). Relative to 5-ASA, patients taking anti-TNF (HR = 1.50 (1.31-1.72)), anti-TNF+TP (HR = 1.56 (1.24-1.95)) or vedolizumab (HR = 1.81 (1.49-2.20)) had an increased hazard of serious infection (p > 0.001). CONCLUSION In a nationwide cohort of IBD patients, we found that risk of serious infections could possibly be affected by behavioural modifications due to SARS-COV-2 pandemic.
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Affiliation(s)
- Nabeel Khan
- Department of Gastroenterology, Corporal Michael J Crescenz
VA Medical Center, Philadelphia, Pennsylvania, USA
- Division of Gastroenterology, University of Pennsylvania,
Perelman School of Medicine, Philadelphia, Pennsylvania, USA
| | - Nadim Mahmud
- Department of Gastroenterology, Corporal Michael J Crescenz
VA Medical Center, Philadelphia, Pennsylvania, USA
- Division of Gastroenterology, University of Pennsylvania,
Perelman School of Medicine, Philadelphia, Pennsylvania, USA
| | - Manthankumar Patel
- Department of Gastroenterology, Corporal Michael J Crescenz
VA Medical Center, Philadelphia, Pennsylvania, USA
| | - Ramaswamy Sundararajan
- Department of Gastroenterology, Corporal Michael J Crescenz
VA Medical Center, Philadelphia, Pennsylvania, USA
| | - Walter Reinisch
- Division of Gastroenterology and Hepatology, Medical
University of Vienna, Vienna, Austria
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19
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Sun X, Yuan Y, Chen L, Ye M, Zheng L. Genetically predicted visceral adipose tissue and risk of nine non-tumour gastrointestinal diseases: evidence from a Mendelian randomization study. Int J Obes (Lond) 2023; 47:406-412. [PMID: 36934207 DOI: 10.1038/s41366-023-01279-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/18/2022] [Revised: 02/09/2023] [Accepted: 02/09/2023] [Indexed: 03/20/2023]
Abstract
BACKGROUND Numerous studies have linked visceral adipose tissue (VAT) to gastrointestinal diseases. However, it remains unclear whether these associations reflect causal relationships. METHODS We used a two-sample Mendelian randomization (MR) approach to elucidate the causal effect of VAT on nine non-tumour gastrointestinal diseases. The inverse-variance weighted method was used to perform the MR analyses. Complementary and multivariable MR analyses were performed to confirm the results. RESULTS Genetically predicted higher VAT was associated with an increased risk of gastro-oesophageal reflux disease (GORD) (odds ratio [OR], 1.21; 95% confidence interval [CI], 1.09-1.34; P = 3.06 × 10-4), duodenal ulcer (DU) (OR, 1.40; 95% CI, 1.10-1.77; P = 0.005), cholelithiasis (OR, 1.75; 95% CI, 1.53-2.00; P = 1.14 × 10-16), and non-alcoholic fatty liver disease (NAFLD) (OR, 2.68; 95% CI, 1.87-3.82; P = 6.26 × 10-8). There were suggestive associations between VAT and gastric ulcer (GU) (OR, 1.22; 95% CI, 1.01-1.48; P = 0.035) and acute pancreatitis (AP) (OR, 1.26; 95% CI, 1.05-1.52; P = 0.013). However, there was little evidence to support the associations between VAT and inflammatory bowel disease, irritable bowel syndrome, or chronic pancreatitis. The associations with GORD, GU, and NAFLD remained in the multivariable MR analyses with adjustment for body mass index (BMI). CONCLUSIONS This study provided evidence in support of causal associations between VAT and GORD, GU, DU, cholelithiasis, AP, and NAFLD. Moreover, the associations between GORD, GU, and NAFLD were independent of the effect of BMI.
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Affiliation(s)
- Xingang Sun
- Department of Cardiology and Atrial Fibrillation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310003, Zhejiang, China
| | - Yifan Yuan
- Department of Gastroenterology, Zhongnan Hospital, Wuhan University, Wuhan, 430071, Hubei, China.,Hubei Clinical Centre and Key Laboratory of Intestinal and Colorectal Diseases, Zhongnan Hospital, Wuhan University, Wuhan, 430071, Hubei, China
| | - Lu Chen
- Department of Cardiology and Atrial Fibrillation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310003, Zhejiang, China
| | - Mei Ye
- Department of Gastroenterology, Zhongnan Hospital, Wuhan University, Wuhan, 430071, Hubei, China. .,Hubei Clinical Centre and Key Laboratory of Intestinal and Colorectal Diseases, Zhongnan Hospital, Wuhan University, Wuhan, 430071, Hubei, China.
| | - Liangrong Zheng
- Department of Cardiology and Atrial Fibrillation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310003, Zhejiang, China.
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20
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Volumetric visceral fat machine learning phenotype on CT for differential diagnosis of inflammatory bowel disease. Eur Radiol 2023; 33:1862-1872. [PMID: 36255487 DOI: 10.1007/s00330-022-09171-x] [Citation(s) in RCA: 13] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2022] [Revised: 08/17/2022] [Accepted: 09/15/2022] [Indexed: 11/04/2022]
Abstract
OBJECTIVES To investigate whether volumetric visceral adipose tissue (VAT) features extracted using radiomics and three-dimensional convolutional neural network (3D-CNN) approach are effective in differentiating Crohn's disease (CD) and ulcerative colitis (UC). METHODS This retrospective study enrolled 316 patients (mean age, 36.25 ± 13.58 [standard deviation]; 219 men) with confirmed diagnosis of CD and UC who underwent CT enterography between 2012 and 2021. Volumetric VAT was semi-automatically segmented on the arterial phase images. Radiomics analysis was performed using principal component analysis (PCA) and the least absolute shrinkage and selection operator (LASSO) logistic regression algorithm. We developed a 3D-CNN model using VAT imaging data from the training cohort. Clinical covariates including age, sex, modified body mass index, and disease duration that impact VAT were added to the machine learning model for adjustment. The model's performance was evaluated on the testing cohort separating from the model's development process by its discrimination and clinical utility. RESULTS Volumetric VAT radiomics analysis with LASSO had the highest AUC value of 0.717 (95% CI, 0.614-0.820), though difference of diagnostic performance among the 3D-CNN model (AUC = 0.693; 95% CI, 0.587-0.798) and radiomics analysis with PCA (AUC = 0.662; 95% CI, 0.548-0.776) and LASSO have not reached statistical significance (all p > 0.05). The radiomics score was higher in UC than in CD on the testing cohort (mean ± SD, UC 0.29 ± 1.05 versus CD -0.60 ± 1.25; p < 0.001). The LASSO model with adjustment of clinical covariates reached an AUC of 0.775 (95%CI, 0.683-0.868). CONCLUSION The developed volumetric VAT-based radiomics and 3D-CNN models provided comparable and effective performance for the characterization of CD from UC. KEY POINTS • High-output feature data extracted from volumetric visceral adipose tissue on CT enterography had an effective diagnostic performance for differentiating Crohn's disease from ulcerative colitis. • With adjustment of clinical covariates that cause difference in volumetric visceral adipose tissue, adjusted clinical machine learning model reached stronger performance when distinguishing Crohn's disease patients from ulcerative colitis patients.
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21
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Gu P, Dube S, McGovern DPB. Medical and Surgical Implications of Mesenteric Adipose Tissue in Crohn's Disease: A Review of the Literature. Inflamm Bowel Dis 2023; 29:458-469. [PMID: 35731568 DOI: 10.1093/ibd/izac120] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/17/2022] [Indexed: 12/09/2022]
Abstract
Mesenteric adipose tissue (MAT) has gained substantial attention as an active player in Crohn's disease (CD), but its clinical significance is poorly understood and likely reflects, in part, difficulties assessing MAT noninvasively. Recent radiologic studies have identified candidate surrogate markers that may reflect inflammatory alterations of MAT in CD and have found that certain features including visceral adipose tissue may inform risk of complicated disease behavior, risk for surgery, and postoperative outcomes. Additionally, emerging surgical data have suggested MAT may even be a therapeutic target to mitigate postoperative recurrence of CD. However, the current studies have variable results, reduced sample sizes, and methodological limitations that preclude incorporating the radiologic and surgical findings into clinical practice. Nonetheless, the results are promising and potentially have important implications for the medical and surgical management of CD, which merits that additional studies are warranted. Thus, we have reviewed the available literature on the medical and surgical implications of MAT in CD to summarize our current understanding and identify gaps in knowledge to inform future investigations.
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Affiliation(s)
- Phillip Gu
- Karsh Division of Gastroenterology, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA
| | - Shishir Dube
- Karsh Division of Gastroenterology, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA
| | - Dermot P B McGovern
- Karsh Division of Gastroenterology, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA
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22
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Lomer MCE, Wilson B, Wall CL. British Dietetic Association consensus guidelines on the nutritional assessment and dietary management of patients with inflammatory bowel disease. J Hum Nutr Diet 2023; 36:336-377. [PMID: 35735908 PMCID: PMC10084145 DOI: 10.1111/jhn.13054] [Citation(s) in RCA: 19] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2021] [Accepted: 06/07/2022] [Indexed: 01/19/2023]
Abstract
BACKGROUND Despite increased awareness of diet and nutrition being integral to the management of patients with inflammatory bowel disease (IBD), there are gaps in the knowledge of IBD healthcare providers regarding nutrition. Furthermore, high quality evidence on nutritional assessment and dietary management of IBD is limited. A Delphi consensus from a panel of experts allows for best-practice guidelines to be developed, especially where high quality evidence is limited. The aim was to develop guidelines for the nutritional assessment and dietary management of IBD using an eDelphi online consensus agreement platform. METHODS Seventeen research topics related to IBD and nutrition were systematically reviewed. Searches in Cochrane, Embase®, Medline® and Scopus® electronic databases were performed. GRADE was used to develop recommendations. Experts from the IBD community (healthcare professionals and patients with IBD) were invited to vote anonymously on the recommendations in a custom-built online platform. Three rounds of voting were carried out with updated iterations of the recommendations and evaluative text based on feedback from the previous round. RESULTS From 23,824 non-duplicated papers, 167 were critically appraised. Fifty-five participants completed three rounds of voting and 14 GRADE statements and 42 practice statements achieved 80% consensus. Comprehensive guidance related to nutrition assessment, nutrition screening and dietary management is provided. CONCLUSIONS Guidelines on the nutritional assessment and dietary management of IBD have been developed using evidence-based consensus to improve equality of care. The statements and practice statements developed demonstrate the level of agreement and the quality and strength of the guidelines.
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Affiliation(s)
- Miranda C E Lomer
- Department of Nutrition and Dietetics, Guy's and St Thomas' NHS Foundation Trust, London, UK.,Department of Nutritional Sciences, King's College London, London, UK
| | - Bridgette Wilson
- Department of Nutrition and Dietetics, Guy's and St Thomas' NHS Foundation Trust, London, UK.,Department of Nutritional Sciences, King's College London, London, UK
| | - Catherine L Wall
- Department of Nutritional Sciences, King's College London, London, UK.,Department of Medicine, University of Otago, Christchurch, New Zealand
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23
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Kakkar C, Singh A, Mahajan R, Midha V, Goyal S, Narang V, Gupta K, Singh D, Bansal N, Saggar K, Sood A. Correlation between magnetic resonance enterography and ileo-colonoscopy for assessment of disease activity in terminal ileal Crohn's disease. Indian J Gastroenterol 2022; 41:465-474. [PMID: 36357600 DOI: 10.1007/s12664-022-01242-7] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/04/2021] [Accepted: 01/13/2022] [Indexed: 11/13/2022]
Abstract
BACKGROUND Magnetic resonance enterography (MRE) has emerged as a novel tool for the assessment of disease activity in Crohn's disease (CD). Real world data from Indian subcontinent on performance of MRE in terminal ileal CD are lacking. METHODS Retrospective analysis of patients with terminal ileal CD who underwent both ileo-colonoscopy and MRE was performed. Ileo-colonoscopy was considered the gold standard for assessment of disease activity. On ileo-colonoscopy, a simple endoscopic score for Crohn's disease (SES-CD) ≥2 was considered active disease; presence of ulcers indicated severe disease. MRE scoring of the disease activity was performed using magnetic resonance index of activity (MARIA) and simplified MARIA (MARIAs). The measure of agreement between ileo-colonoscopy and MRE and comparison of MARIA and MARIAs for assessment of disease activity and sensitivity of MRE to detect mucosal ulcerations were calculated. RESULTS Seventy patients with terminal ileal CD (mean age 40.74±15.56 years; 71.4% males [n=50]) were evaluated. The sensitivities of MARIA and MARIAs scores to detect active disease were 0.76 and 0.84, respectively. The area under the receiver operating characteristic curve (AUROC) for detecting severe disease was 0.836 (p<0.0001) for MARIA and 0.861 (p<0.0001) for MARIAs. For mild active disease, there was no agreement between SES-CD and MARIA or MARIAs; however, for severe disease, the agreement was fair and moderate for MARIA and MARIAs, respectively. MARIA and MARIAs were comparable for identification of active and severe disease (κ 0.759, p<0.0001 and κ 0.840, p<0.0001, respectively). MRE was 68.18% sensitive to detect mucosal ulcers. CONCLUSION MRE is a reliable and sensitive tool for detection of endoscopically severe, but not mild, terminal ileal CD.
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Affiliation(s)
- Chandan Kakkar
- Department of Radiology and Radiodiagnosis, Dayanand Medical College, Ludhiana, 141 001, India
| | - Arshdeep Singh
- Department of Gastroenterology, Dayanand Medical College, Ludhiana, 141 001, India
| | - Ramit Mahajan
- Department of Gastroenterology, Dayanand Medical College, Ludhiana, 141 001, India
| | - Vandana Midha
- Department of Internal Medicine, Dayanand Medical College, Ludhiana, 141 001, India
| | - Shriya Goyal
- Mayo Clinic, 200 First St. SW, Rochester, MN, 55905, USA
| | - Vikram Narang
- Department of Pathology, Dayanand Medical College, Ludhiana, 141 001, India
| | - Kamini Gupta
- Department of Radiology and Radiodiagnosis, Dayanand Medical College, Ludhiana, 141 001, India
| | - Dharmatma Singh
- Department of Gastroenterology, Dayanand Medical College, Ludhiana, 141 001, India
| | - Namita Bansal
- Research and Development Center, Dayanand Medical College, Ludhiana, 141 001, India
| | - Kavita Saggar
- Department of Radiology and Radiodiagnosis, Dayanand Medical College, Ludhiana, 141 001, India
| | - Ajit Sood
- Department of Gastroenterology, Dayanand Medical College, Ludhiana, 141 001, India.
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24
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Gu P, Luo J, Kim J, Paul P, Limketkai B, Sauk JS, Park S, Parekh N, Zheng K, Rudrapatna V, Syal G, Ha C, McGovern DP, Melmed GY, Fleshner P, Eisenstein S, Ramamoorthy S, Dulai PS, Boland BS, Grunvald E, Mahadevan U, Ohno-Machado L, Sandborn WJ, Singh S. Effect of Obesity on Risk of Hospitalization, Surgery, and Serious Infection in Biologic-Treated Patients With Inflammatory Bowel Diseases: A CA-IBD Cohort Study. Am J Gastroenterol 2022; 117:1639-1647. [PMID: 35973139 DOI: 10.14309/ajg.0000000000001855] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/16/2022] [Accepted: 04/22/2022] [Indexed: 12/11/2022]
Abstract
INTRODUCTION Obesity is variably associated with treatment response in biologic-treated patients with inflammatory bowel diseases (IBD). We evaluated the association between obesity and risk of hospitalization, surgery, or serious infections in patients with IBD in new users of biologic agents in a large, multicenter, electronic health record (EHR)-based cohort (CA-IBD). METHODS We created an EHR-based cohort of adult patients with IBD who were new users of biologic agents (tumor necrosis factor [TNF-α] antagonists, ustekinumab, and vedolizumab) between January 1, 2010, and June 30, 2017, from 5 health systems in California. Patients were classified as those with normal body mass index (BMI), overweight, or obese based on the World Health Organization classification. We compared the risk of all-cause hospitalization, IBD-related surgery, or serious infections among patients with obesity vs those overweight vs those with normal BMI, using Cox proportional hazard analyses, adjusting for baseline demographic, disease, and treatment characteristics. RESULTS Of 3,038 biologic-treated patients with IBD (69% with Crohn's disease and 76% on TNF-α antagonists), 28.2% (n = 858) were overweight, and 13.7% (n = 416) were obese. On a follow-up after biologic initiation, obesity was not associated with an increased risk of hospitalization (adjusted hazard ratio [aHR] vs normal BMI, 0.90; [95% confidence interval, 0.72-1.13]); IBD-related surgery (aHR, 0.62 [0.31-1.22]); or serious infection (aHR, 1.11 [0.73-1.71]). Similar results were observed on stratified analysis by disease phenotype (Crohn's disease vs ulcerative colitis) and index biologic therapy (TNF-α antagonists vs non-TNF-α antagonists). DISCUSSION In a multicenter, EHR-based cohort of biologic-treated patients with IBD, obesity was not associated with hospitalization, surgery, or serious infections. Further studies examining the effect of visceral obesity on patient-reported and endoscopic outcomes are needed.
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Affiliation(s)
- Phillip Gu
- Karsh Division of Gastroenterology and Hepatology, Department of Medicine, Cedars-Sinai Medical System, Los Angeles, California, USA
| | - Jiyu Luo
- Division of Biostatistics and Bioinformatics, Department of Family Medicine and Public Health, UC San Diego, La Jolla, California, USA
| | - Jihoon Kim
- Division of Biomedical Informatics, Department of Medicine, UC San Diego, La Jolla, California, USA
| | - Paulina Paul
- Division of Biomedical Informatics, Department of Medicine, UC San Diego, La Jolla, California, USA
| | - Berkeley Limketkai
- Vatche and Tamar Manoukian Division of Digestive Diseases, Department of Medicine, UC Los Angeles, Los Angeles, California, USA
| | - Jenny S Sauk
- Vatche and Tamar Manoukian Division of Digestive Diseases, Department of Medicine, UC Los Angeles, Los Angeles, California, USA
| | - Sunhee Park
- Division of Gastroenterology, Department of Medicine, UC Irvine, Orange, California, USA
| | - Nimisha Parekh
- Division of Gastroenterology, Department of Medicine, UC Irvine, Orange, California, USA
| | - Kai Zheng
- Department of Informatics, Donald Bren School of Information and Computer Sciences, UC Irvine, Orange, California, USA
| | - Vivek Rudrapatna
- Division of Gastroenterology, Department of Medicine, UC San Francisco, California, USA
| | - Gaurav Syal
- Karsh Division of Gastroenterology and Hepatology, Department of Medicine, Cedars-Sinai Medical System, Los Angeles, California, USA
| | - Christina Ha
- Karsh Division of Gastroenterology and Hepatology, Department of Medicine, Cedars-Sinai Medical System, Los Angeles, California, USA
| | - Dermot P McGovern
- Karsh Division of Gastroenterology and Hepatology, Department of Medicine, Cedars-Sinai Medical System, Los Angeles, California, USA
| | - Gil Y Melmed
- Karsh Division of Gastroenterology and Hepatology, Department of Medicine, Cedars-Sinai Medical System, Los Angeles, California, USA
| | - Phillip Fleshner
- Division of Colorectal Surgery, Department of Surgery, Cedars-Sinai Medical System, Los Angeles, California, USA
| | - Samuel Eisenstein
- Division of Colon and Rectal Surgery, Department of Surgery, UC San Diego, La Jolla, California, USA
| | - Sonia Ramamoorthy
- Division of Colon and Rectal Surgery, Department of Surgery, UC San Diego, La Jolla, California, USA
| | - Parambir S Dulai
- Division of Gastroenterology, Department of Medicine, UC San Diego, La Jolla, California, USA
| | - Brigid S Boland
- Division of Gastroenterology, Department of Medicine, UC San Diego, La Jolla, California, USA
| | - Eduardo Grunvald
- Division of General Internal Medicine, Department of Medicine, UC San Diego, La Jolla, California, USA
| | - Uma Mahadevan
- Division of Gastroenterology, Department of Medicine, UC San Francisco, California, USA
| | - Lucila Ohno-Machado
- Division of Biomedical Informatics, Department of Medicine, UC San Diego, La Jolla, California, USA
| | - William J Sandborn
- Division of Gastroenterology, Department of Medicine, UC San Diego, La Jolla, California, USA
| | - Siddharth Singh
- Division of Biomedical Informatics, Department of Medicine, UC San Diego, La Jolla, California, USA
- Division of Gastroenterology, Department of Medicine, UC San Diego, La Jolla, California, USA
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25
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Xiong Z, Zhou Z, Hao L, Li Y, Hu X, Hu D, Luo Y, Wang Y, Shen Y, Li Z. The relationship between perianal fistula activity and abdominal adipose tissue in Crohn’s disease: an observational study. Insights Imaging 2022; 13:156. [PMID: 36153465 PMCID: PMC9509502 DOI: 10.1186/s13244-022-01293-6] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2022] [Accepted: 09/04/2022] [Indexed: 11/10/2022] Open
Abstract
Abstract
Objective
The aim of this study was to analyze the relationship between abdominal adipose tissue and perianal fistula activity in patients with Crohn's disease (CD) using cross-sectional imaging.
Methods
Patients with perianal fistulizing CD who underwent pelvic magnetic resonance imaging (MRI) and abdominal computed tomography (CT) were retrospectively enrolled. We scored the fistulas in each patient's MRI images based on Van Assche's classification. The area and density of subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) (at the third, fourth, and fifth lumbar (L3, L4, and L5) levels were measured by averaging five slices of measurements at each vertebral level in CT images, and areas were further standardized by the lumbar height2 (heightL1-5). The VAT/SAT ratio (VSR) and VAT/Total adipose tissue (VA/TA) index were calculated. Based on MRI scores, patients were divided into two groups with low and high activity, and their clinical, MRI features, and CT parameters were compared. We evaluated patients with follow-up MRI and compared the differences in clinical and radiological indicators among patients with different outcomes.
Results
Overall, 136 patients were included, 77 in the low-activity group and 59 in the high-activity group. Patients in the high activity group had lower subcutaneous adipose index (all levels, p < 0.05) and visceral adipose index (L3 level, p < 0.01), but higher SAT and VAT density (all levels, p < 0.01), VSR (L5 level, p = 0.07) and VA/TA index (L5 level, p < 0.05).
Conclusion
There were differences in adipose tissue composition among CD patients with different active perianal fistulas.
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26
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Boronat-Toscano A, Monfort-Ferré D, Menacho M, Caro A, Bosch R, Espina B, Algaba-Chueca F, Saera-Vila A, Moliné A, Marti M, Espin E, Millan M, Serena C. Anti-TNF Therapies Suppress Adipose Tissue Inflammation in Crohn’s Disease. Int J Mol Sci 2022; 23:ijms231911170. [PMID: 36232469 PMCID: PMC9570367 DOI: 10.3390/ijms231911170] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2022] [Revised: 09/19/2022] [Accepted: 09/19/2022] [Indexed: 11/16/2022] Open
Abstract
Anti-TNF biologics have been shown to markedly improve the quality of life for patients with Crohn’s disease (CD), yet one-third of patients fail to benefit from this treatment. Patients with CD develop a characteristic wrapping of visceral adipose tissue (VAT) in the inflamed intestinal area, termed creeping fat, and it is known that adipose tissue expansion influences the efficacy of anti-TNF drugs. We questioned whether anti-TNF therapies impact the creeping fat in CD, which might affect the outcome of the disease. Adipose tissue biopsies were obtained from a cohort of 14 patients with CD that received anti-TNF drugs and from 29 non-anti-TNF-treated patients (control group) matched by sex, age, and body mass index undergoing surgical interventions for symptomatic complications. We found that anti-TNF therapies restored adipose tissue morphology and suppressed immune cell infiltration in the creeping fat. Additionally, anti-TNF treatments appeared to markedly improve the pro-inflammatory phenotype of adipose-tissue macrophages and adipose-tissue-derived stem cells. Our study provides evidence that anti-TNF medications influence immune cells and progenitor cells in the creeping of patients with CD, suppressing inflammation. We propose that perilesional VAT should be considered when administering anti-TNF therapy in patients with CD.
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Affiliation(s)
- Albert Boronat-Toscano
- Institut d’Investigació Sanitària Pere Virgili, Hospital Universitari Joan XXIII, Universitat Rovira i Virgili, 43007 Tarragona, Spain
| | - Diandra Monfort-Ferré
- Institut d’Investigació Sanitària Pere Virgili, Hospital Universitari Joan XXIII, Universitat Rovira i Virgili, 43007 Tarragona, Spain
| | - Margarita Menacho
- Digestive Unit, Hospital Universitari Joan XXIII, 43007 Tarragona, Spain
| | - Aleidis Caro
- Colorectal Surgery Unit, Hospital Universitari Joan XXIII, 43007 Tarragona, Spain
| | - Ramon Bosch
- Department of Pathology, Oncological Pathology and Bioinformatics Research Group, Hospital de Tortosa Verge de la Cinta—IISPV, 43500 Tortosa, Spain
| | - Beatriz Espina
- Colorectal Surgery Unit, Hospital Universitari Joan XXIII, 43007 Tarragona, Spain
| | - Francisco Algaba-Chueca
- Institut d’Investigació Sanitària Pere Virgili, Hospital Universitari Joan XXIII, Universitat Rovira i Virgili, 43007 Tarragona, Spain
| | | | - Alicia Moliné
- Digestive Unit, Hospital Universitari Joan XXIII, 43007 Tarragona, Spain
| | - Marc Marti
- Colorectal Surgery Unit, General Surgery Service, Hospital Valle de Hebron, Universitat Autonoma de Barcelona, 08035 Barcelona, Spain
| | - Eloy Espin
- Colorectal Surgery Unit, General Surgery Service, Hospital Valle de Hebron, Universitat Autonoma de Barcelona, 08035 Barcelona, Spain
| | - Mónica Millan
- Colorectal Surgery Unit, General Surgery Service, Hospital La Fe, 46026 Valencia, Spain
| | - Carolina Serena
- Institut d’Investigació Sanitària Pere Virgili, Hospital Universitari Joan XXIII, Universitat Rovira i Virgili, 43007 Tarragona, Spain
- Correspondence: or
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Chen D, Lu MM, Wang JH, Ren Y, Xu LL, Cheng WX, Wang SS, Li XL, Cheng XF, Gao JG, Kalyani FS, Jin X. High-fat diet aggravates colitis via mesenteric adipose tissue derived exosome metastasis-associated lung adenocarcinoma transcript 1. World J Gastroenterol 2022; 28:3838-3853. [PMID: 36157545 PMCID: PMC9367221 DOI: 10.3748/wjg.v28.i29.3838] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/04/2021] [Revised: 04/28/2022] [Accepted: 07/06/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Obesity is associated with an increased risk of developing Crohn's disease (CD), higher disease activity, and comparatively worse clinical outcomes. AIM To investigate the role of mesenteric adipose tissue-derived exosomes in the pathogenesis of CD aggravation in obese individuals. METHODS First, we induced colitis in mice initiated on high-fat and normal diets and compared the severity of colitis. We then extracted and identified exosomes from mesenteric adipose tissue and determined the levels of metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) in mesenteric adipose tissue-derived exosomes and the colon. Next, we demonstrated an interaction between MALAT1 and the miR-15a-5p/activating transcription factor 6 (ATF6) axis. Finally, we explored the effects of mesenteric adipose tissue-derived exosomes extracted from mice fed a high-fat or normal diet on the severity of 2,4,6-trinitrobe-nzenesulfonic acid (TNBS)-induced colitis and ATF6-related endoplasmic reticulum stress pathways. RESULTS High-fat diet was found to aggravate TNBS-induced colitis in mice. The expression of MALAT1 in mesenteric adipose tissue-derived exosomes of high-fat diet-fed mice increased. The increased expression of MALAT1 in colon tissue exacerbated TNBS-induced colitis and activated the ATF6 endoplasmic reticulum stress pathway. This effect was partially reversed by the reduced expression of MALAT1 and overexpression of miR-15a-5p. CONCLUSION Mesenteric adipose tissue-derived exosome-encapsulated long noncoding RNAs MALAT1 targets the colon and aggravates TNBS-induced colitis in obese mice, which may potentially act on the miR-15a-5p/ATF6 axis and activate endoplasmic reticulum stress.
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Affiliation(s)
- Dong Chen
- Department of Colorectal Surgery, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, Zhejiang Province, China
| | - Miao-Miao Lu
- Department of Medicine, Zhejiang University School of Medicine, Hangzhou 310003, Zhejiang Province, China
| | - Jin-Hai Wang
- Department of Colorectal Surgery, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, Zhejiang Province, China
| | - Yue Ren
- Department of Medicine, Zhejiang University School of Medicine, Hangzhou 310003, Zhejiang Province, China
| | - Ling-Ling Xu
- Department of Medicine, Zhejiang University School of Medicine, Hangzhou 310003, Zhejiang Province, China
| | - Wei-Xin Cheng
- Department of Medicine, Zhejiang University School of Medicine, Hangzhou 310003, Zhejiang Province, China
| | - Sai-Sai Wang
- Department of Colorectal Surgery, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, Zhejiang Province, China
| | - Xiao-Lin Li
- Department of Emergency, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, Zhejiang Province, China
| | - Xiao-Fei Cheng
- Department of Colorectal Surgery, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, Zhejiang Province, China
| | - Jian-Guo Gao
- Department of Gastroenterology, The First affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, Zhejiang Province, China
| | - Farhin Shaheed Kalyani
- Department of Medicine, Zhejiang University School of Medicine, Hangzhou 310003, Zhejiang Province, China
| | - Xi Jin
- Department of Gastroenterology, The First affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, Zhejiang Province, China
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28
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Zhang Z, Yu X, Fang N, Long X, Ruan X, Qiu J, Tao S, Gong P, Nie K, Li A, Wang X, Tian L. Can visceral adipose tissue and skeletal muscle predict recurrence of newly diagnosed Crohn's disease in different treatments. BMC Gastroenterol 2022; 22:250. [PMID: 35585617 PMCID: PMC9116006 DOI: 10.1186/s12876-022-02327-5] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/08/2021] [Accepted: 05/06/2022] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND AND AIMS It is crucial to manage the recurrence of Crohn's disease (CD). This study is aimed to explore whether visceral adipose tissue (VAT) and skeletal muscle (SM) are associated with the recurrence of CD upon different treatments. METHODS All patients with a definite diagnosis of CD were retrospectively divided into three groups according to distinct treatment regimens: 5-amino salicylic acid group (Group A), steroids + azathioprine (Group B) and biologics (Group C). The pretreatment computerized tomography (CT) images and clinical data were collected. The VAT area, mesenteric fat index (MFI), the ratio of VAT area to fat mass (VAT area/FM) were assessed. The primary end point was the recurrence of CD within 1 year of follow-up. RESULTS A total of 171 CD patients were enrolled, including 57 (33.33%) patients in Group A, 70 (40.94%) patients in Group B and 44 (25.73%) patients in Group C. Patients with 1-year recurrence had higher MFI (P = 0.011) and VAT area/FM (P = 0.000). ROC curve demonstrated that patients with the ratio of VAT area/FM and MFI higher than 0.578 and 1.394 tended to have recurrence with the AUC of 0.707 and 0.709. Similar results could be observed in Group A & B but not in Group C. CONCLUSIONS High VAT area/FM and MFI are related to recurrence within 1 year for newly diagnosed CD patients treated by 5-amino salicylic or azathioprine + steroids rather than biologics. We could not observe any radiological data associated with the recurrence of CD patients under biological treatment.
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Affiliation(s)
- Zinan Zhang
- Department of Gastroenterology, The Third Xiangya Hospital of Central South University, 138 Tongzipo Road, Changsha, 410013, Hunan, China
| | - Xiaoyu Yu
- Department of Gastroenterology, The Third Xiangya Hospital of Central South University, 138 Tongzipo Road, Changsha, 410013, Hunan, China
| | - Ning Fang
- Department of Gastroenterology, The Third Xiangya Hospital of Central South University, 138 Tongzipo Road, Changsha, 410013, Hunan, China
| | - Xiuyan Long
- Department of Gastroenterology, The Third Xiangya Hospital of Central South University, 138 Tongzipo Road, Changsha, 410013, Hunan, China
| | - Xixian Ruan
- Department of Gastroenterology, The Third Xiangya Hospital of Central South University, 138 Tongzipo Road, Changsha, 410013, Hunan, China
| | - Jianing Qiu
- Department of Gastroenterology, The Third Xiangya Hospital of Central South University, 138 Tongzipo Road, Changsha, 410013, Hunan, China
| | - Sifan Tao
- Department of Gastroenterology, The Third Xiangya Hospital of Central South University, 138 Tongzipo Road, Changsha, 410013, Hunan, China
| | - Pan Gong
- Department of Gastroenterology, The Third Xiangya Hospital of Central South University, 138 Tongzipo Road, Changsha, 410013, Hunan, China
| | - Kai Nie
- Department of Gastroenterology, The Third Xiangya Hospital of Central South University, 138 Tongzipo Road, Changsha, 410013, Hunan, China
| | - An Li
- Department of Gastroenterology, The Third Xiangya Hospital of Central South University, 138 Tongzipo Road, Changsha, 410013, Hunan, China
| | - Xiaoyan Wang
- Department of Gastroenterology, The Third Xiangya Hospital of Central South University, 138 Tongzipo Road, Changsha, 410013, Hunan, China.
| | - Li Tian
- Department of Gastroenterology, The Third Xiangya Hospital of Central South University, 138 Tongzipo Road, Changsha, 410013, Hunan, China.
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29
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Gu P, Chhabra A, Chittajallu P, Chang C, Mendez D, Gilman A, Fudman DI, Xi Y, Feagins LA. Visceral Adipose Tissue Volumetrics Inform Odds of Treatment Response and Risk of Subsequent Surgery in IBD Patients Starting Antitumor Necrosis Factor Therapy. Inflamm Bowel Dis 2022; 28:657-666. [PMID: 34291800 DOI: 10.1093/ibd/izab167] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/05/2021] [Indexed: 12/12/2022]
Abstract
BACKGROUND Data describing the effect of obesity on antitumor necrosis factor (anti-TNF) treatment response are inconsistent. Visceral adipose tissue (VAT) is a superior marker of adiposity to body mass index. However, its effect on treatment response is unclear. We aimed to evaluate the effect of VAT on anti-TNF treatment response. METHODS Inflammatory bowel disease (IBD) patients starting anti-TNF agents between January 1, 2009, and July 31, 2019, were included. 3-dimensional measurements of VAT volume and visceral fat index (visceral:subcutaneous adipose tissue ratio; VFI) were obtained from computed tomography (CT) scans. Subjects were categorized by predefined volume cutoffs (<1500cm3, 1500-2999cm3, ≥3000cm3) and VFI (<0.33, 0.33-0.66, ≥0.67). Primary outcomes included a composite treatment response end point at 6 and 12 months. Secondary outcomes were surgery at 6 and 12 months. Multivariable logistic regression was used to calculate adjusted odds ratio (aOR) and 95% confidence interval (CI). RESULTS The final cohort included 176 patients. No significant differences in treatment response at 6 months was observed. At 12 months, compared with volume <1500cm3, patients with volume 1500-2999cm3 had higher odds of response (aOR, 3.52; 95% CI, 1.16-10.71; P = .023), whereas volume ≥3000cm3 did not. Compared with VFI<0.33, VFI ≥0.67 had higher odds of surgery at 6 (aOR, 48.22; 95% CI, 4.73-491.57; P = .023) and 12 months (aOR, 20.94; 95% CI, 3.14-139.67; P = .004). Post hoc analysis suggested VAT may affect drug pharmacokinetics. CONCLUSIONS We found VAT volume is associated with anti-TNF treatment response in a nondose dependent manner, and VFI may inform risk of surgery after anti-TNF initiation. If confirmed by prospective studies, VAT volumetrics are potentially useful biomarkers to inform IBD treatment decisions.
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Affiliation(s)
- Phillip Gu
- Division of Digestive and Liver Diseases, UT Southwestern, Dallas,TX, USA.,Department of Internal Medicine, UT Southwestern, Dallas,TX, USA
| | - Avneesh Chhabra
- Division of Musculoskeletal Radiology, Department of Radiology, UT Southwestern, Dallas,TX, USA
| | | | | | - Denisse Mendez
- Department of Internal Medicine, UT Southwestern, Dallas,TX, USA
| | - Andrew Gilman
- Division of Digestive and Liver Diseases, UT Southwestern, Dallas,TX, USA.,Department of Internal Medicine, UT Southwestern, Dallas,TX, USA
| | - David I Fudman
- Division of Digestive and Liver Diseases, UT Southwestern, Dallas,TX, USA.,Department of Internal Medicine, UT Southwestern, Dallas,TX, USA
| | - Yin Xi
- Division of Musculoskeletal Radiology, Department of Radiology, UT Southwestern, Dallas,TX, USA.,Department of Population and Data Sciences, UT Southwestern, Dallas,TX, USA
| | - Linda A Feagins
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of Texas at Austin Dell Medical School, Austin,TX, USA
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30
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Chan SSM, Chen Y, Casey K, Olen O, Ludvigsson JF, Carbonnel F, Oldenburg B, Gunter MJ, Tjønneland A, Grip O, Lochhead P, Chan AT, Wolk A, Khalili H. Obesity is Associated With Increased Risk of Crohn's disease, but not Ulcerative Colitis: A Pooled Analysis of Five Prospective Cohort Studies. Clin Gastroenterol Hepatol 2022; 20:1048-1058. [PMID: 34242756 DOI: 10.1016/j.cgh.2021.06.049] [Citation(s) in RCA: 41] [Impact Index Per Article: 13.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/19/2021] [Revised: 06/24/2021] [Accepted: 06/25/2021] [Indexed: 12/12/2022]
Abstract
BACKGROUND AND AIMS It is unclear whether obesity is associated with the development of inflammatory bowel disease despite compelling data from basic science studies. We therefore examined the association between obesity and risk of Crohn's disease (CD) and ulcerative colitis (UC). METHODS We conducted pooled analyses of 5 prospective cohorts with validated anthropometric measurements for body mass index (BMI) and waist-hip ratio and other lifestyle factors. Diagnoses of CD and UC were confirmed through medical records or ascertained using validated definitions. We used Cox proportional hazards modeling to calculate pooled multivariable-adjusted HRs (aHRs) and 95% confidence intervals (CIs). RESULTS Among 601,009 participants (age range, 18-98 years) with 10,110,018 person-years of follow-up, we confirmed 563 incident cases of CD and 1047 incident cases of UC. Obesity (baseline BMI ≥30 kg/m2) was associated with an increased risk of CD (pooled aHR, 1.34; 95% CI, 1.05-1.71, I2 = 0%) compared with normal BMI (18.5 to <25 kg/m2). Each 5 kg/m2 increment in baseline BMI was associated with a 16% increase in risk of CD (pooled aHR, 1.16; 95% CI, 1.05-1.22; I2 = 0%). Similarly, with each 5 kg/m2 increment in early adulthood BMI (age, 18-20 years), there was a 22% increase in risk of CD (pooled aHR, 1.22; 95% CI, 1.05-1.40; I2 = 13.6%). An increase in waist-hip ratio was associated with an increased risk of CD that did not reach statistical significance (pooled aHR across quartiles, 1.08; 95% CI, 0.97-1.19; I2 = 0%). No associations were observed between measures of obesity and risk of UC. CONCLUSIONS In an adult population, obesity as measured by BMI was associated with an increased risk of older-onset CD but not UC.
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Affiliation(s)
- Simon S M Chan
- Department of Gastroenterology, Norfolk and Norwich University Hospital NHS Trust, Norwich, United Kingdom; Department of Medicine, Bob Champion Research and Education Building, Norwich Medical School, University of East Anglia, Norwich, United Kingdom.
| | - Ye Chen
- Clinical and Translational Epidemiology Unit, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts
| | - Kevin Casey
- Clinical and Translational Epidemiology Unit, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts
| | - Ola Olen
- Clinical Epidemiology Division, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden; Department of Clinical Science and Education, Södersjukhuset, Karolinska Institutet, Stockholm, Sweden; Department of Pediatric Gastroenterology and Nutrition, Sachs' Children and Youth Hospital, Stockholm, Sweden
| | - Jonas F Ludvigsson
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Department of Paediatrics, Örebro University Hospital, Örebro, Sweden
| | - Franck Carbonnel
- Service de Gastroentérologie, Centre hospitalier Universitaire de Bicêtre, Assistance Publique Hôpitaux de Paris, Université Paris Saclay, Le Kremlin Bicêtre, France; INSERM U1018, Villejuif, France
| | - Bas Oldenburg
- Department of Gastroenterology and Hepatology, University Medical Centre Utrecht, Utrecht, The Netherlands
| | - Marc J Gunter
- Section of Nutrition and Metabolism, International Agency for Research on Cancer - WHO, Lyon, France
| | - Anne Tjønneland
- Danish Cancer Society Research Center, Copenhagen, Denmark; Department of Public Health, University of Copenhagen, Denmark
| | - Olof Grip
- Department of Gastroenterology, Skåne University Hospital, Malmö, Sweden
| | - Paul Lochhead
- Clinical and Translational Epidemiology Unit, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts; Gastroenterology Unit, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts
| | - Andrew T Chan
- Clinical and Translational Epidemiology Unit, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts; Gastroenterology Unit, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts
| | - Alicia Wolk
- Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden; Department of Surgical Sciences, Uppsala University, Uppsala, Sweden
| | - Hamed Khalili
- Clinical and Translational Epidemiology Unit, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts; Gastroenterology Unit, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts; Broad Institute of MIT and Harvard, Cambridge, Massachusetts
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31
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Yang Z, Xu W, Zhai R, Li T, Ning Z, Pawitan Y, Shen X. Integration of Distinct Analysis Strategies Improves Tissue-Trait Association Identification. Front Genet 2022; 13:798269. [PMID: 35444688 PMCID: PMC9014299 DOI: 10.3389/fgene.2022.798269] [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: 10/19/2021] [Accepted: 02/07/2022] [Indexed: 11/14/2022] Open
Abstract
Integrating genome-wide association studies (GWAS) with transcriptomic data, human complex traits and diseases have been linked to relevant tissues and cell types using different methods. However, different results from these methods generated confusion while no gold standard is currently accepted, making it difficult to evaluate the discoveries. Here, applying three methods on the same data source, we estimated the sensitivity and specificity of these methods in the absence of a gold standard. We established a more specific tissue-trait association atlas by combining the information captured by different methods. Our triangulation strategy improves the performance of existing methods in establishing tissue-trait associations. The results provide better etiological and functional insights for the tissues underlying different human complex traits and diseases.
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Affiliation(s)
- Zhijian Yang
- Biostatistics Group, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, China.,Center for Intelligent Medicine Research, Greater Bay Area Institute of Precision Medicine (Guangzhou), Fudan University, Guangzhou, China
| | - Wenzheng Xu
- Biostatistics Group, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, China
| | - Ranran Zhai
- Biostatistics Group, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, China.,Center for Intelligent Medicine Research, Greater Bay Area Institute of Precision Medicine (Guangzhou), Fudan University, Guangzhou, China
| | - Ting Li
- Biostatistics Group, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, China.,Center for Intelligent Medicine Research, Greater Bay Area Institute of Precision Medicine (Guangzhou), Fudan University, Guangzhou, China
| | - Zheng Ning
- Biostatistics Group, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, China.,Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
| | - Yudi Pawitan
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
| | - Xia Shen
- Biostatistics Group, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, China.,Center for Intelligent Medicine Research, Greater Bay Area Institute of Precision Medicine (Guangzhou), Fudan University, Guangzhou, China.,Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.,State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, China.,Centre for Global Health Research, Usher Institute, University of Edinburgh, Edinburgh, United Kingdom
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32
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Ando K, Uehara K, Sugiyama Y, Kobayashi Y, Murakami Y, Sato H, Kunogi T, Sasaki T, Takahashi K, Ueno N, Kashima S, Moriichi K, Tanabe H, Okumura T, Fujiya M. Correlation Among Body Composition Parameters and Long-Term Outcomes in Crohn's Disease After Anti-TNF Therapy. Front Nutr 2022; 9:765209. [PMID: 35433773 PMCID: PMC9010511 DOI: 10.3389/fnut.2022.765209] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2021] [Accepted: 01/26/2022] [Indexed: 11/28/2022] Open
Abstract
BACKGROUND The impact of the body composition on the pathophysiology and clinical course of Crohn's disease (CD) has not been fully elucidated. AIMS To reveal the correlations among body composition and long-term outcomes in CD after anti-TNF therapy. METHODS Ninety-one patients who received anti-TNF therapy as their first biologic treatment were enrolled. The skeletal muscle index (SMI), visceral and subcutaneous fat area (VFA, SFA), and the ratio of the VFA to SFA (mesenteric fat index; MFI) at the 3rd lumbar level were measured using computed tomography (CT) imaging before the induction. The correlation among the body composition and outcomes were retrospectively analyzed. RESULTS The 5-year cumulative secondary failure- and resection-free rates in patients with a low SMI (39.1% and 64.8%) were significantly lower than those with a high SMI (67.5% and 92.7%; p = 0.0071 and 0.0022, respectively). The 5-year cumulative secondary failure-free rate in the patients with low VF (45.0%) was significantly lower than that in those with high VF (77.6%; p = 0.016), and the 5-year cumulative resection-free rate in patients with a high MFI (68.9%) was significantly lower than that in those with a low MFI (83.0%; p = 0.031). Additionally, patients with low age and BMI had significantly lower cumulative secondary failure- and resection-free rates than those with high age and BMI (low age: 37.4% and 71.2%; high age: 70.7% and 88.9%; p = 0.0083 and 0.027, respectively) (low BMI: 27.2% and 64.8%; high BMI: 68.3% and 87.9%; p = 0.014 and 0.030, respectively), respectively. In the multivariate analyses, a low SMI was the only independent risk factor for secondary failure (hazard ratio [HR] 2.15, 95% confidence interval [CI] 1.04-4.44), while low age (HR 4.06, 95% CI 1.07-15.4), a low SMI (HR 4.19, 95% CI 1.01-17.3) and high MFI were risk factors for bowel resection (HR 4.31, 95% CI 1.36-13.7). CONCLUSION The skeletal muscle mass and ratio of visceral to subcutaneous fat were suggested to reflect the long-term clinical outcome and may be helpful as prognostic markers after anti-TNF therapy in CD.
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Affiliation(s)
- Katsuyoshi Ando
- Gastroenterology and Endoscopy, Division of Metabolism and Biosystemic Science, Gastroenterology and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, Asahikawa, Japan
| | - Kyoko Uehara
- Gastroenterology and Endoscopy, Division of Metabolism and Biosystemic Science, Gastroenterology and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, Asahikawa, Japan
| | - Yuya Sugiyama
- Gastroenterology and Endoscopy, Division of Metabolism and Biosystemic Science, Gastroenterology and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, Asahikawa, Japan
| | - Yu Kobayashi
- Gastroenterology and Endoscopy, Division of Metabolism and Biosystemic Science, Gastroenterology and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, Asahikawa, Japan
| | - Yuki Murakami
- Gastroenterology and Endoscopy, Division of Metabolism and Biosystemic Science, Gastroenterology and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, Asahikawa, Japan
| | - Hiroki Sato
- Gastroenterology and Endoscopy, Division of Metabolism and Biosystemic Science, Gastroenterology and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, Asahikawa, Japan
| | - Takehito Kunogi
- Gastroenterology and Endoscopy, Division of Metabolism and Biosystemic Science, Gastroenterology and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, Asahikawa, Japan
| | - Takahiro Sasaki
- Gastroenterology and Endoscopy, Division of Metabolism and Biosystemic Science, Gastroenterology and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, Asahikawa, Japan
| | - Keitaro Takahashi
- Gastroenterology and Endoscopy, Division of Metabolism and Biosystemic Science, Gastroenterology and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, Asahikawa, Japan
| | - Nobuhiro Ueno
- Gastroenterology and Endoscopy, Division of Metabolism and Biosystemic Science, Gastroenterology and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, Asahikawa, Japan
| | - Shin Kashima
- Gastroenterology and Endoscopy, Division of Metabolism and Biosystemic Science, Gastroenterology and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, Asahikawa, Japan
| | - Kentaro Moriichi
- Gastroenterology and Endoscopy, Division of Metabolism and Biosystemic Science, Gastroenterology and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, Asahikawa, Japan
| | - Hiroki Tanabe
- Cancer Genome, Division of Metabolism and Biosystemic Science, Gastroenterology and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, Asahikawa, Japan
| | - Toshikatsu Okumura
- Division of Metabolism and Biosystemic Science, Gastroenterology and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, Asahikawa, Japan
| | - Mikihiro Fujiya
- Gastroenterology and Endoscopy, Division of Metabolism and Biosystemic Science, Gastroenterology and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, Asahikawa, Japan
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33
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Suau R, Pardina E, Domènech E, Lorén V, Manyé J. The Complex Relationship Between Microbiota, Immune Response and Creeping Fat in Crohn's Disease. J Crohns Colitis 2022; 16:472-489. [PMID: 34528668 DOI: 10.1093/ecco-jcc/jjab159] [Citation(s) in RCA: 31] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
In the last decade, there has been growing interest in the pathological involvement of hypertrophic mesenteric fat attached to the serosa of the inflamed intestinal segments involved in Crohn's disease [CD], known as creeping fat. In spite of its protective nature, creeping fat harbours an aberrant inflammatory activity which, in an already inflamed intestine, may explain why creeping fat is associated with a greater severity of CD. The transmural inflammation of CD facilitates the interaction of mesenteric fat with translocated intestinal microorganisms, contributing to activation of the immune response. This may be not the only way in which microorganisms alter the homeostasis of this fatty tissue: intestinal dysbiosis may also impair xenobiotic metabolism. All these CD-related alterations have a functional impact on nuclear receptors such as the farnesoid X receptor or the peroxisome proliferator-activated receptor γ, which are implicated in regulation of the immune response, adipogenesis and the maintenance of barrier function, as well as on creeping fat production of inflammatory-associated cells such as adipokines. The dysfunction of creeping fat worsens the inflammatory course of CD and may favour intestinal fibrosis and fistulizing complications. However, our current knowledge of the pathophysiology and pathogenic role of creeping fat is controversial and a better understanding might provide new therapeutic targets for CD. Here we aim to review and update the key cellular and molecular alterations involved in this inflammatory process that link the pathological components of CD with the development of creeping fat.
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Affiliation(s)
- Roger Suau
- IBD Research Group, 'Germans Trias i Pujol' Research Institute (IGTP), Badalona (Catalonia), Spain.,Centro de Investigación Biomédica en Red (CIBER), Madrid, Spain
| | - Eva Pardina
- Biochemistry and Molecular Biomedicine Department, University of Barcelona, Barcelona (Catalonia), Spain
| | - Eugeni Domènech
- IBD Research Group, 'Germans Trias i Pujol' Research Institute (IGTP), Badalona (Catalonia), Spain.,Centro de Investigación Biomédica en Red (CIBER), Madrid, Spain.,Gastroenterology Department, 'Germans Trias i Pujol' University Hospital, Badalona (Catalonia), Spain
| | - Violeta Lorén
- IBD Research Group, 'Germans Trias i Pujol' Research Institute (IGTP), Badalona (Catalonia), Spain.,Centro de Investigación Biomédica en Red (CIBER), Madrid, Spain
| | - Josep Manyé
- IBD Research Group, 'Germans Trias i Pujol' Research Institute (IGTP), Badalona (Catalonia), Spain.,Centro de Investigación Biomédica en Red (CIBER), Madrid, Spain
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Islam MR, Arthur S, Haynes J, Butts MR, Nepal N, Sundaram U. The Role of Gut Microbiota and Metabolites in Obesity-Associated Chronic Gastrointestinal Disorders. Nutrients 2022; 14:624. [PMID: 35276983 PMCID: PMC8838694 DOI: 10.3390/nu14030624] [Citation(s) in RCA: 23] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2021] [Revised: 01/13/2022] [Accepted: 01/28/2022] [Indexed: 11/16/2022] Open
Abstract
The gut microbiota is a complex community of microorganisms that has become a new focus of attention due to its association with numerous human diseases. Research over the last few decades has shown that the gut microbiota plays a considerable role in regulating intestinal homeostasis, and disruption to the microbial community has been linked to chronic disease conditions such as inflammatory bowel disease (IBD), colorectal cancer (CRC), and obesity. Obesity has become a global pandemic, and its prevalence is increasing worldwide mostly in Western countries due to a sedentary lifestyle and consumption of high-fat/high-sugar diets. Obesity-mediated gut microbiota alterations have been associated with the development of IBD and IBD-induced CRC. This review highlights how obesity-associated dysbiosis can lead to the pathogenesis of IBD and CRC with a special focus on mechanisms of altered absorption of short-chain fatty acids (SCFAs).
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Affiliation(s)
| | | | | | | | | | - Uma Sundaram
- Department of Clinical and Translational Sciences, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV 25701, USA; (M.R.I.); (S.A.); (J.H.); (M.R.B.); (N.N.)
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Zhou Z, Xiong Z, Shen Y, Li Z, Hu X, Hu D. Magnetic resonance imaging-based body composition is associated with nutritional and inflammatory status: a longitudinal study in patients with Crohn's disease. Insights Imaging 2021; 12:178. [PMID: 34862942 PMCID: PMC8643393 DOI: 10.1186/s13244-021-01121-3] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2021] [Accepted: 11/01/2021] [Indexed: 12/21/2022] Open
Abstract
Objective To evaluate the changes in magnetic resonance imaging-based body composition parameters during follow-ups in patients with Crohn's disease (CD). Methods Between November 1, 2017, and June 30, 2021, patients diagnosed with CD, who underwent two or more magnetic resonance enterography (MRE) scans at our institution were retrospectively reviewed. The baseline and one subsequent follow-up scan for each patient were paired to form longitudinal comparisons. Skeletal muscle, visceral adipose tissue (VAT), and subcutaneous adipose tissue (SAT) indexes were calculated from tissue areas measured at the third lumbar vertebra level per scan, standardized by dividing the height2 and lumbar height2 (heightL1–L5). We also assessed the correlation between changes in VAT to total adipose tissue ratio (VA/TA index) and CD activity scores (5-point MRE classification) using Spearman’s correlation analysis. A multivariate linear regression model was used to adjust for the follow-up duration and treatment type. Results Overall, 49 patients (with 49 paired scans) were enrolled. VA/TA index changes were negatively correlated with changes in skeletal muscle index (SMI; r = − 0.339, p < 0.05). The VA/TA index (52.69 ± 10.66% vs. 49.18 ± 10.80%, p < 0.001) and the total MRE score (8.0 ± 3.9 vs. 5.7 ± 3.4, p < 0.001) decreased significantly during follow-up, regardless of follow-up duration and treatment type (both p > 0.05). Changes in total MRE score were negatively correlated with SMI changes (r = − 0.408, p < 0.01) but positively correlated with VA/TA index changes (r = 0.479, p < 0.01). Conclusion An increase in SMI and a decrease in VA/TA index could reflect improved nutritional and inflammatory status. Supplementary Information The online version contains supplementary material available at 10.1186/s13244-021-01121-3.
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Affiliation(s)
- Ziling Zhou
- Department of Radiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Qiaokou District, Wuhan, 430030, Hubei, China.,Biomedical Engineering Department, College of Life Sciences and Technology, Huazhong University of Science and Technology, Wuhan, China
| | - Ziman Xiong
- Department of Radiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Qiaokou District, Wuhan, 430030, Hubei, China
| | - Yaqi Shen
- Department of Radiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Qiaokou District, Wuhan, 430030, Hubei, China.
| | - Zhen Li
- Department of Radiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Qiaokou District, Wuhan, 430030, Hubei, China
| | - Xuemei Hu
- Department of Radiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Qiaokou District, Wuhan, 430030, Hubei, China
| | - Daoyu Hu
- Department of Radiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Qiaokou District, Wuhan, 430030, Hubei, China
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Abstract
BACKGROUND Rates of obesity are increasing worldwide, as is the incidence of inflammatory bowel disease (IBD). Obesity is now considered an inflammatory state. Visceral adiposity in particular may be associated with a more severe inflammatory phenotype in IBD. AIM The aim of this review article is to summarise the current literature on the association between visceral adiposity and outcomes in inflammatory bowel disease METHODS: To collect relevant articles, PubMed/MEDLINE and Embase searches were performed using Boolean search phrases. Grey literature and manual searches were also performed. Abstracts were selected by two independent reviewers based on pre-determined criteria. Full text articles were reviewed, and data extracted and assessed. RESULTS One hundred twenty-seven abstracts were obtained through the initial search, with 85 abstracts reviewed and 22 full text articles included. Characteristics are included in Table 1. Most of these were retrospective studies and of moderate or weak quality. Studies suggested visceral fat content is higher in Crohn's disease than in healthy controls. Visceral adiposity was associated with an increased risk of complex Crohn's disease phenotype (OR 26.1 95% CI 2-75.4; p = 0.02). Post-operative recurrence was higher in patients with higher visceral fat indices (RR 2.1; CI 1.5-3; p = 0.012). There were conflicting data regarding the effect of visceral adiposity on post-operative complications and the efficacy of medical therapy. Table 1 Study characteristics Author Year Country Study type Study numbers Control group Disease type Methodology e.g. CT Body composition measurements Results Argeny [24] 2018 Austria Retrospective cohort N = 95 N/A Crohn's disease CT; L3 level Visceral fat area (cm2) Visceral fat index (VFA/m2) No association between VFA or VFI and short-term post-operative outcomes Bryant [30] 2018 Australia Prospective cohort N = 110 N/A Crohn's disease and UC DXA Visceral adipose tissue (VAT) (cm3) Visceral adipose tissue (grams) VAT/height index (cm3/m2) VAT:subcutaneous adipose tissue ratio Fat mass index (kg/m2) VAT and VHI increased significantly over 24 months Bryant [13] 2018 Australia Prospective cohort N = 72 N/A Crohn's disease; female DXA Visceral adipose tissue (VAT) (cm3) Visceral adipose tissue (grams) VAT/height index (cm3/m2) VAT:subcutaneous adipose tissue ratio VAT:SAT positively associated with stricturing disease Adiposity not associated with fistulising disease phenotype VAT:SAT significantly associated with faecal calprotectin in L3 phenotype VAT:SAT significantly negatively associated with VHI and QoL over 24 months Buning [25] 2015 Germany Case control N = 50 N = 19 healthy controls Crohn's disease MRI US VAT Thickness of abdominal fat Distance to posterior wall of aorta Area of inferior part of perirenal fat VAT accumulation was higher in CD patients vs healthy controls VAT and VAT/fat mass ratio higher in patients in short-term remission vs long-term remission VAT/FM higher in stricturing/fistulising disease vs inflammatory subtype No association between VAT/FM and CDAI, HBI or anti-TNF treatment Connolly [26] 2014 US Retrospective cohort N = 143 N/A Crohn's disease CT (L1-L5 level) Visceral/intra-abdominal adiposity (VA) Subcutaneous adiposity (SA) VA not associated with post-operative morbidity Decreased SA and increased visceral/subcutaneous ratio were predictive of post-op complications. (p = 0.02; p < 0.001) Cravo [27] 2017 Portugal Retrospective cohort N = 71 N/A Crohn's disease CT (L3 level) Smooth muscle area (cm2) Visceral fat area (cm2) Subcutaneous fat area (cm2) Visceral fat index Muscle radiation attenuation L2 phenotype associated with lower muscle attenuation and higher visceral fat index (non-significant) B2/B3/surgery - significantly lower muscle attenuation. VFI associated with increased risk of complicated phenotype. (OR 26.1; 95% CI 1-75; p = 0.02) Ding [17] 2016 US Retrospective cohort N = 164 N/A Crohn's disease CT (L3 level) Visceral fat area (cm2) Subcutaneous fat area Total fat area Visceral obesity associated with longer duration of surgery, increased intra-operative blood loss and longer length of bowel resected Higher complication rates in patients with visceral obesity (p < 0.001) VFA independent risk factor of adverse post-op outcomes Ding [14] 2017 Retrospective cohort N = 106 N/A Crohn's disease CT (L3 level) Visceral fat area Subcutaneous fat area Skeletal muscle area Skeletal muscle index Visceral obesity and myopenic obesity not significantly associated with risk of primary non-response Body composition factors not associated with secondary loss of response Erhayiem [18] 2011 UK Retrospective cohort N = 50 N/A Crohn's disease CT (L4 level) Mesenteric fat index (visceral:subcutaneous area ratio)N = 50 Mesenteric fat index was significantly higher in complicated Crohn's disease. ROC analysis for MFI in identifying complicated Crohn's disease: AUC = 0.95 (95% CI 0.89-1.0) Feng [28] 2018 China Retrospective cohort N = 80 Non-IBD GI patients Crohn's disease CT-energy spectral Visceral fat area (cm2) Subcutaneous fat area (cm2) Mesenteric fat index No significant difference in VFA between Crohn's disease cohort and control group. (p = 0.669). ROC analysis: detection of disease based on VFA and MFI: AUC 0.776 Sensitivity 77.5% Specificity 67.5% Hafraoui [16] 1998 France/Belgium Prospective N = 43 Healthy volunteers n = 13 Intestinal resection n = 9 Crohn's disease MRI (umbilicus) Total abdominal fat (cm2) Intra-abdominal fat (cm2) Subcutaneous fat (cm2) Ratio of intra-abdominal:total fat area was significantly higher in patients with Crohn's vs controls. (p = 0.012) No correlation between abdominal fat tissue and disease activity, duration or steroid therapy Holt [29] 2017 Australia/New Zealand RCT N = 44 N = 11 placebo group Crohn's disease CT/MRI (L3, L4-5 levels) Visceral adipose tissue area Subcutaneous adipose tissue area Skeletal muscle area Visceral adipose tissue/height index VHI > 1.5 times gender mean was specific for endoscopic recurrence (100%) with sensitivity of 29%. PPV = 1 (0.59-1.00) There was no significant difference in disease activity at 18 months post-resection based on VHI > 1.5 gender mean Li [31] 2015 China Retrospective cohort N = 72 N/A Crohn's disease CT (umbilicus) Visceral fat area (cm2) Subcutaneous fat area (cm2) Mesenteric fat index Post-op recurrence was more frequent with high VFA values. (p = 0.019) VFA and MFI were independent risk factors for post-operative recurrence. (p = 0.013 and p = 0.028, respectively) High VFA and high MFI were significantly higher in patients with endoscopic activity (p = 0.023) Liu [32] 2016 Retrospective case-control N = 59 N = 30 (< 15% increase VFA) IBD with IPAA CT (L3) Visceral fat area Subcutaneous fat area No difference in pouchitis, pouch sinus formation and composite adverse pouch outcomes between the 2 groups with and without VFA increase > 15%. Excessive VAT gain was an independent risk factor for the composite adverse pouch outcomes. (OR 12.6 (95% CI 1.19-133.5) Magro [33] 2018 Brazil Cross-sectional study N = 78 N = 28 Health control Crohn's disease DEXA Fat and lean masses Visceral fat (kg) Visceral fat/BMI Visceral fat per %body fat VF was higher in Crohn's disease group (p = 0.004) compared to controls Parmentier-Decrucq [34] 2009 Prospective study N = 132 N/A Crohn's disease MRI Subcutaneous fat Visceral fat Total abdominal fat increased 18% in Crohn's disease patients treated with infliximab induction therapy Shen [35] 2018 China Retrospective N = 97 N/A Crohn's disease CT (umbilicus) Subcutaneous fat area Visceral fat area Mesenteric fat index VFA and MFI were significantly lower in patients with mucosal healing (post-infliximab). (p < 0.0001) SFA was not significantly different VFA correlated with CDAI (p < 0.001) and was an independent predictive factor for mucosal healing Stidham [15] 2015 Retrospective N = 269 N/A Crohn's disease CT(T10-L5) Subcutaneous fat volume Visceral fat volume No significant difference in visceral fat volume between patients with surgical complications Thiberge [36] 2018 France Retrospective N = 149 N/A Crohn's disease CT (L3 level) Skeletal muscle index Visceral adiposity index Subcutaneous adiposity index SAI and VAI were significantly lower in patients who underwent surgery or who died in 6 months post-CT(p = 0.009 and p < 0.001) VanDerSloot [37] 2017 Cohort study N/A Crohn's disease CT (T11-S5) Visceral adipose tissue volume Non-significant trend toward increased risk of surgery and penetrating disease with increasing VAT Wei [38] 2018 China Retrospective N = 86 N/A IBD post-resection CT (L3 level) Visceral adipose volume Subcutaneous adipose volume Increased visceral:subcutaneous fat ratio was associated with increased procalcitonin levels on post-op days 1, 3 and 5 Yadav [39] 2017 India Prospective N = 97 N/A IBD CT (L4 level) Visceral fat area Subcutaneous fat area No statistically significant correlation between visceral fat and disease behaviour in Crohn's disease N/A not applicable, VFA visceral fat area, VFI visceral fat index, VAT visceral adipose tissue, VHI visceral adipose tissue to height index, SAT subcutaneous adipose tissue, DXA dual-energy X-ray absorptiometry, CT computer tomography, MRI magnetic resonance imaging, US ultrasound, CDAI Crohn's disease activity index, HBI Harvey-Bradshaw Index, anti-TNF anti-tumour necrosis factor, SA subcutaneous adiposity, ROC receiver operating curve, AUC area under the curve, MFI mesenteric fat index, SAI subcutaneous adiposity index, PPV positive predictive value CONCLUSION: Visceral adiposity appears to be increased in Crohn's disease with some evidence that it is also associated with more complex disease phenotypes. There is also a signal that post-operative recurrence rates are affected by increasing mesenteric adiposity. There is a relative lack of data in UC patients and further high-quality studies are necessary to elucidate the relationship between visceral adiposity and IBD and the implications for patient outcomes.
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Böhm SK. Excessive Body Weight and Diverticular Disease. Visc Med 2021; 37:372-382. [PMID: 34722720 PMCID: PMC8543333 DOI: 10.1159/000518674] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2021] [Accepted: 07/23/2021] [Indexed: 01/17/2023] Open
Abstract
BACKGROUND The worldwide proportion of overweight adults almost doubled from 22% in 1975 to 39% in 2016. Comparably, for the USA and Germany in 2016, the proportion was 68 and 56.8%, respectively. In Olmsted County, Minnesota, the prevalence of diverticulitis also doubled between 1980 and 2007, from 19 to 40%. Obesity substantially increases the risk of multiple gastrointestinal (GI) diseases and non-GI diseases. In a narrative review, we examined the evidence on whether obesity also increases the risk for the development of diverticulosis or diverticular disease and its outcome. SUMMARY Evidence suggests that being overweight (body mass index ≥25 kg/m2) or obese (≥30 kg/m2), especially viscerally obese, is a risk factor for diverticulosis, diverticular disease and diverticulitis, diverticular bleeding, more severe or complicated disease, recurrent disease, and for worse outcomes after surgery. KEY MESSAGES There is a well-founded association between overweight and diverticular disease as well as diverticulosis. It is not clear whether overweight per se or confounders linked with it are responsible for the association. However, means to fight the overweight and obesity epidemic might also help to reduce the prevalence of morbidity and mortality from diverticular disease.
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Affiliation(s)
- Stephan K. Böhm
- Klinik Innere Medizin/Gastroenterologie, Spital Bülach, Bülach, Switzerland
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38
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Zhou Z, Xiong Z, Xie Q, Xiao P, Zhang Q, Gu J, Li J, Hu D, Hu X, Shen Y, Li Z. Computed tomography-based multiple body composition parameters predict outcomes in Crohn's disease. Insights Imaging 2021; 12:135. [PMID: 34564786 PMCID: PMC8464641 DOI: 10.1186/s13244-021-01083-6] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2021] [Accepted: 08/16/2021] [Indexed: 01/04/2023] Open
Abstract
Background The efficacy of computed tomography-based multiple body composition parameters in assessing disease behavior and prognosis has not been comprehensively evaluated in Crohn’s disease. This study aimed to assess the association of body composition parameters with disease behavior and outcomes in Crohn’s disease and to compare the efficacies of indexes derived from body and lumbar spinal heights in body composition analysis. Results One hundred twenty-two patients with confirmed Crohn’s disease diagnoses and abdominal computed tomography scans were retrospectively included in this study. Skeletal muscle, visceral, and subcutaneous fat indexes were calculated by dividing each type of tissue area by height2 and lumbar spinal height2. Parameters reflecting the distribution of adiposity were also assessed. Principal component analysis was used to deal with parameters with multicollinearity. Patients were grouped according to their disease behavior (inflammatory vs. structuring/penetrating) and outcomes. Adverse outcome included need for intestinal surgery or anti-TNF therapy. Predictors of disease course from multiple parameters were evaluated using multivariate analysis. Indexes derived from body and lumbar spinal heights were strongly correlated (r, 0.934–0.995; p < 0.001). Low skeletal muscle-related parameters were significantly associated with complicated disease behavior in multivariate analysis (p = 0.048). Complicated disease behavior (p < 0.001) and adipose tissue parameters-related first principal component (p = 0.029) were independent biomarkers for predicting adverse outcomes. Conclusions Skeletal muscle and adipose tissue principle component were associated with complicated Crohn’s disease behavior and adverse outcome, respectively. Indexes derived from body and lumbar spinal heights have similar efficacies in body composition analysis. Supplementary Information The online version contains supplementary material available at 10.1186/s13244-021-01083-6.
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Affiliation(s)
- Ziling Zhou
- Department of Radiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, 430030, Hubei, China.,Biomedical Engineering Department, College of Life Sciences and Technology, Huazhong University of Science and Technology, Wuhan, China
| | - Ziman Xiong
- Department of Radiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, 430030, Hubei, China
| | - Qingguo Xie
- Biomedical Engineering Department, College of Life Sciences and Technology, Huazhong University of Science and Technology, Wuhan, China
| | - Peng Xiao
- Biomedical Engineering Department, College of Life Sciences and Technology, Huazhong University of Science and Technology, Wuhan, China
| | - Qingpeng Zhang
- School of Data Science, City University of Hong Kong, Kowloon, Hong Kong, China
| | - Jian Gu
- Department of Anesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Jing Li
- Biomedical Engineering Department, College of Life Sciences and Technology, Huazhong University of Science and Technology, Wuhan, China
| | - Daoyu Hu
- Department of Radiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, 430030, Hubei, China
| | - Xuemei Hu
- Department of Radiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, 430030, Hubei, China
| | - Yaqi Shen
- Department of Radiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, 430030, Hubei, China.
| | - Zhen Li
- Department of Radiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, 430030, Hubei, China
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Crohn's Disease Increases the Mesothelial Properties of Adipocyte Progenitors in the Creeping Fat. Int J Mol Sci 2021; 22:ijms22084292. [PMID: 33924264 PMCID: PMC8074767 DOI: 10.3390/ijms22084292] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2021] [Revised: 04/13/2021] [Accepted: 04/16/2021] [Indexed: 12/14/2022] Open
Abstract
Our understanding of the interplay between human adipose tissue and the immune system is limited. The mesothelium, an immunologically active structure, emerged as a source of visceral adipose tissue. After investigating the mesothelial properties of human visceral and subcutaneous adipose tissue and their progenitors, we explored whether the dysfunctional obese and Crohn's disease environments influence the mesothelial/mesenchymal properties of their adipocyte precursors, as well as their ability to mount an immune response. Using a tandem transcriptomic/proteomic approach, we evaluated the mesothelial and mesenchymal expression profiles in adipose tissue, both in subjects covering a wide range of body-mass indexes and in Crohn's disease patients. We also isolated adipose tissue precursors (adipose-derived stem cells, ASCs) to assess their mesothelial/mesenchymal properties, as well as their antigen-presenting features. Human visceral tissue presented a mesothelial phenotype not detected in the subcutaneous fat. Only ASCs from mesenteric adipose tissue, named creeping fat, had a significantly higher expression of the hallmark mesothelial genes mesothelin (MSLN) and Wilms' tumor suppressor gene 1 (WT1), supporting a mesothelial nature of these cells. Both lean and Crohn's disease visceral ASCs expressed equivalent surface percentages of the antigen-presenting molecules human leucocyte antigen-DR isotype (HLA-DR) and CD86. However, lean-derived ASCs were predominantly HLA-DR dim, whereas in Crohn's disease, the HLA-DR bright subpopulation was increased 3.2-fold. Importantly, the mesothelial-enriched Crohn's disease precursors activated CD4+ T-lymphocytes. Our study evidences a mesothelial signature in the creeping fat of Crohn's disease patients and its progenitor cells, the latter being able to present antigens and orchestrate an immune response.
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Basson AR, Chen C, Sagl F, Trotter A, Bederman I, Gomez-Nguyen A, Sundrud MS, Ilic S, Cominelli F, Rodriguez-Palacios A. Regulation of Intestinal Inflammation by Dietary Fats. Front Immunol 2021; 11:604989. [PMID: 33603741 PMCID: PMC7884479 DOI: 10.3389/fimmu.2020.604989] [Citation(s) in RCA: 32] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2020] [Accepted: 12/11/2020] [Indexed: 12/12/2022] Open
Abstract
With the epidemic of human obesity, dietary fats have increasingly become a focal point of biomedical research. Epidemiological studies indicate that high-fat diets (HFDs), especially those rich in long-chain saturated fatty acids (e.g., Western Diet, National Health Examination survey; NHANES 'What We Eat in America' report) have multi-organ pro-inflammatory effects. Experimental studies have confirmed some of these disease associations, and have begun to elaborate mechanisms of disease induction. However, many of the observed effects from epidemiological studies appear to be an over-simplification of the mechanistic complexity that depends on dynamic interactions between the host, the particular fatty acid, and the rather personalized genetics and variability of the gut microbiota. Of interest, experimental studies have shown that certain saturated fats (e.g., lauric and myristic fatty acid-rich coconut oil) could exert the opposite effect; that is, desirable anti-inflammatory and protective mechanisms promoting gut health by unanticipated pathways. Owing to the experimental advantages of laboratory animals for the study of mechanisms under well-controlled dietary settings, we focus this review on the current understanding of how dietary fatty acids impact intestinal biology. We center this discussion on studies from mice and rats, with validation in cell culture systems or human studies. We provide a scoping overview of the most studied diseases mechanisms associated with the induction or prevention of Inflammatory Bowel Disease in rodent models relevant to Crohn's Disease and Ulcerative Colitis after feeding either high-fat diet (HFD) or feed containing specific fatty acid or other target dietary molecule. Finally, we provide a general outlook on areas that have been largely or scarcely studied, and assess the effects of HFDs on acute and chronic forms of intestinal inflammation.
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Affiliation(s)
- Abigail R. Basson
- Division of Gastroenterology and Liver Diseases, School of Medicine, Case Western Reserve University School of Medicine, Cleveland, OH, United States
- Digestive Health Research Institute, School of Medicine, Case Western Reserve University, Cleveland, OH, United States
- Cleveland Digestive Diseases Research Core, School of Medicine, Case Western Reserve University, Cleveland, OH, United States
- Digestive Health Institute, University Hospitals Cleveland Medical Center, Cleveland, OH, United States
| | - Christy Chen
- Digestive Health Research Institute, School of Medicine, Case Western Reserve University, Cleveland, OH, United States
| | - Filip Sagl
- Digestive Health Research Institute, School of Medicine, Case Western Reserve University, Cleveland, OH, United States
| | - Ashley Trotter
- Division of Gastroenterology and Liver Diseases, School of Medicine, Case Western Reserve University School of Medicine, Cleveland, OH, United States
- Digestive Health Research Institute, School of Medicine, Case Western Reserve University, Cleveland, OH, United States
- Department of Hospital Medicine, Pritzker School of Medicine, NorthShore University Health System, Chicago, IL, United States
| | - Ilya Bederman
- Department of Genetics and Genome Sciences, Case Western Reserve University, Cleveland, OH, United States
| | - Adrian Gomez-Nguyen
- Division of Gastroenterology and Liver Diseases, School of Medicine, Case Western Reserve University School of Medicine, Cleveland, OH, United States
- Digestive Health Research Institute, School of Medicine, Case Western Reserve University, Cleveland, OH, United States
- Cleveland Digestive Diseases Research Core, School of Medicine, Case Western Reserve University, Cleveland, OH, United States
| | - Mark S. Sundrud
- Department of Immunology and Microbiology, The Scripps Research Institute, Jupiter, FL, United States
| | - Sanja Ilic
- Department of Human Sciences, Human Nutrition, College of Education and Human Ecology, The Ohio State University, Columbus, OH, United States
| | - Fabio Cominelli
- Division of Gastroenterology and Liver Diseases, School of Medicine, Case Western Reserve University School of Medicine, Cleveland, OH, United States
- Digestive Health Research Institute, School of Medicine, Case Western Reserve University, Cleveland, OH, United States
- Cleveland Digestive Diseases Research Core, School of Medicine, Case Western Reserve University, Cleveland, OH, United States
- Digestive Health Institute, University Hospitals Cleveland Medical Center, Cleveland, OH, United States
| | - Alex Rodriguez-Palacios
- Division of Gastroenterology and Liver Diseases, School of Medicine, Case Western Reserve University School of Medicine, Cleveland, OH, United States
- Digestive Health Research Institute, School of Medicine, Case Western Reserve University, Cleveland, OH, United States
- Cleveland Digestive Diseases Research Core, School of Medicine, Case Western Reserve University, Cleveland, OH, United States
- Digestive Health Institute, University Hospitals Cleveland Medical Center, Cleveland, OH, United States
- University Hospitals Research and Education Institute, University Hospitals Cleveland Medical Center, Cleveland, OH, United States
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de Carvalho LGF, Lima WG, Coelho LGV, Cardoso VN, Fernandes SOA. Circulating Leptin Levels as a Potential Biomarker in Inflammatory Bowel Diseases: A Systematic Review and Meta-Analysis. Inflamm Bowel Dis 2021; 27:169-181. [PMID: 32095814 DOI: 10.1093/ibd/izaa037] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/23/2019] [Indexed: 12/20/2022]
Abstract
BACKGROUND The differential diagnosis of inflammatory bowel diseases (IBDs) between Crohn's disease (CD) and ulcerative colitis (UC) is important for designing an effective therapeutic regimen. However, without any adequate gold standard method for differential diagnosis currently, therapeutic design remains a major challenge in clinical practice. In this context, recent studies have showed that circulating leptin stands out as a potential biomarker for the categorization of IBDs. Thus, we aimed to summarize the current understanding of the prognostic and diagnostic value of serum leptin in patients with IBDs. METHODS A systematic search was performed in PubMed/MEDLINE, Scopus, Cochrane Library, and Web of Science databases. Articles that aimed to study the relationship between circulating levels of leptin and IBDs were included. Finally, the meta-analysis was performed with the mean serum leptin levels in patients with IBDs and healthy controls using RevMan 5.3 software, with I2 > 50% as a criterion for substantial heterogeneity. RESULTS Nineteen studies were included. Serum leptin levels among patients with IBDs and healthy controls did not show a significant difference (95% CI, -2.15 to 0.57; I2, 86%, P ≤ 0.00001). Similarly, there was no association of leptin levels with the activity of IBDs (95% CI, -0.24 to 0.06; I2, 50%; P = 0.13). However, serum leptin levels were significantly higher in patients with CD than those in patients with UC (95% CI, -2.09 to -0.37; I2, 7%; P ≤ 0.36). CONCLUSION This review suggested that serum leptin levels might be a promising biomarker to help in the differentiation between CD and UC.
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Affiliation(s)
- Larissa Gabriela Ferreira de Carvalho
- Laboratório de radioisótopos, Departamento de Análises Clínicas e Toxicológicas, Faculdade de Farmácia, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil
| | - William Gustavo Lima
- Laboratório de radioisótopos, Departamento de Análises Clínicas e Toxicológicas, Faculdade de Farmácia, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil
| | - Luiz Gonzaga Vaz Coelho
- Instituto ALFA de Gastrenterologia, Hospital das Clínicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil
| | - Valbert Nascimento Cardoso
- Laboratório de radioisótopos, Departamento de Análises Clínicas e Toxicológicas, Faculdade de Farmácia, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil
| | - Simone Odília Antunes Fernandes
- Laboratório de radioisótopos, Departamento de Análises Clínicas e Toxicológicas, Faculdade de Farmácia, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil
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Li XH, Feng ST, Cao QH, Coffey JC, Baker ME, Huang L, Fang ZN, Qiu Y, Lu BL, Chen ZH, Li Y, Bettenworth D, Iacucci M, Sun CH, Ghosh S, Rieder F, Chen MH, Li ZP, Mao R. Degree of Creeping Fat Assessed by Computed Tomography Enterography is Associated with Intestinal Fibrotic Stricture in Patients with Crohn's Disease: A Potentially Novel Mesenteric Creeping Fat Index. J Crohns Colitis 2021; 15:1161-1173. [PMID: 33411893 PMCID: PMC8427713 DOI: 10.1093/ecco-jcc/jjab005] [Citation(s) in RCA: 49] [Impact Index Per Article: 12.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
BACKGROUND AND AIMS Emerging evidence points to a link between creeping fat and the pathogenesis of Crohn's disease [CD]. Non-invasive assessment of the severity of creeping fat on cross-sectional imaging modality has seldom been investigated. This study aimed to develop and characterize a novel mesenteric creeping fat index [MCFI] based on computed tomography [CT] in CD patients. METHODS MCFI was developed based on vascular findings on CT in a retrospective cohort [n = 91] and validated in a prospective cohort [n = 30]. The severity of creeping fat was graded based on the extent to which mesenteric fat extended around the intestinal circumference using the vessels in the fat as a marker. The accuracy of MCFI was assessed by comparing it with the degree of creeping fat observed in surgical specimens. The relationship between MCFI and fibrostenosis was characterized by determining if these correlated. The accuracy of MCFI was compared with other radiographic indices [i.e. visceral to subcutaneous fat area ratio and fibrofatty proliferation score]. RESULTS In the retrospective cohort, MCFI had moderate accuracy in differentiating moderate-severe from mild fibrostenosis (area under the receiver operating characteristic [ROC] curve [AUC] = 0.799; p = 0.000). ROC analysis in the retrospective cohort identified a threshold MCFI of > 3 which accurately differentiated fibrostenosis severity in the prospective cohort [AUC = 0.756; p = 0.018]. An excellent correlation was shown between MCFI and the extent of fat wrapping in specimens in the prospective cohort [r = 0.840, p = 0.000]. Neither visceral to subcutaneous fat area ratio nor fibrofatty proliferation score correlated well with the degree of intestinal fibrosis. CONCLUSIONS MCFI can accurately characterize the extent of mesenteric fat wrapping in surgical specimens. It may become another non-invasive measure of CD fibrostenosis.
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Affiliation(s)
- Xue-Hua Li
- Department of Radiology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, People’s Republic of China
| | - Shi-Ting Feng
- Department of Radiology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, People’s Republic of China
| | - Qing-Hua Cao
- Department of Pathology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, People’s Republic of China
| | - J Calvin Coffey
- Department of Surgery, University Hospital Group Limerick and School of Medicine, University of Limerick, Limerick, Ireland
| | - Mark E Baker
- Section of Abdominal Imaging, Imaging Institute, Digestive Disease Institute and Cancer Institute, Cleveland Clinic, Cleveland, Ohio, USA
| | - Li Huang
- Department of Radiology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, People’s Republic of China
| | - Zhuang-Nian Fang
- Department of Radiology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, People’s Republic of China
| | - Yun Qiu
- Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, People’s Republic of China
| | - Bao-Lan Lu
- Department of Radiology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, People’s Republic of China
| | - Zhi-Hui Chen
- Department of Gastrointestinal and Pancreatic Surgery, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, People’s Republic of China
| | - Yi Li
- Center for Inflammatory Bowel Diseases, Department of General Surgery, Jinling Hospital, Medical School of Nanjing University, Nanjing, Jiangsu, People’s Republic of China
| | - Dominik Bettenworth
- Department of Medicine B for Gastroenterology and Hepatology, University Hospital Münster, Münster, Germany
| | - Marietta Iacucci
- NIHR Biomedical Research Institute, Institute of Translational Medicine, University of Birmingham and University Hospitals Birmingham NHS Foundation Trust, UK
| | - Can-Hui Sun
- Department of Radiology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, People’s Republic of China
| | - Subrata Ghosh
- NIHR Biomedical Research Institute, Institute of Translational Medicine, University of Birmingham and University Hospitals Birmingham NHS Foundation Trust, UK
| | - Florian Rieder
- Department of Gastroenterology, Hepatology and Nutrition, Digestive Diseases and Surgery Institute, Cleveland Clinic, Cleveland, Ohio, USA
| | - Min-Hu Chen
- Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, People’s Republic of China
| | - Zi-Ping Li
- Department of Radiology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, People’s Republic of China
| | - Ren Mao
- Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, People’s Republic of China,Department of Gastroenterology, Hepatology and Nutrition, Digestive Diseases and Surgery Institute, Cleveland Clinic, Cleveland, Ohio, USA,Corresponding author: Ren Mao, The First Affiliated Hospital, Sun Yat-Sen University, 58 Zhongshan Road 2nd, Guangzhou 510080, People’s Republic of China; Department of Gastroenterology, Hepatology and Nutrition, Digestive Diseases and Surgery Institute, Cleveland Clinic, Cleveland, Ohio, USA. Tel: 86-20-87755766-8471; Fax: 86-20-87615805;
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Serum adipokines as non-invasive biomarkers in Crohn's disease. Sci Rep 2020; 10:18027. [PMID: 33093517 PMCID: PMC7582883 DOI: 10.1038/s41598-020-74999-6] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2020] [Accepted: 09/23/2020] [Indexed: 12/30/2022] Open
Abstract
Adipose tissue secretes molecules that can promote activity in Crohn’s disease. We aimed to evaluate the role of serum adipokines as possible biomarkers in Crohn’s disease. Serum samples were obtained from 40 patients with endoscopically active or quiescent Crohn’s disease and 36 healthy controls. Serum leptin, ghrelin, resistin and adiponectin levels were analysed by Multiplex in a Luminex 200 system technology. Receiver Operating Characteristic curves were performed to evaluate the adipokines discriminatory capacity. A logistic regression adjusted by possible confounders (i.e. gender, age, BMI) was performed for those adipokines that showed an area under the curve > 0.7. No differences were found in age, gender or BMI among groups. Distribution for serum resistin was different among the three groups of study, and only this adipokine showed an area under the curve of 0.75 comparing actives patients and healthy control groups. Resistin median concentration was selected as a cut-off for a logistic regression analysis; odds ratio along its 95% confidence interval adjusted by gender, age, and BMI yielded a value of 5.46 (1.34–22.14) comparing actives patients and healthy controls. High concentration of serum resistin is probably associated to activity, being this association independent of gender, age or BMI.
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Kurowski JA, Achkar JP, Gupta R, Barbur I, Bonfield TL, Worley S, Remer EM, Fiocchi C, Viswanath SE, Kay MH. Adipokine Resistin Levels at Time of Pediatric Crohn Disease Diagnosis Predict Escalation to Biologic Therapy. Inflamm Bowel Dis 2020; 27:1088-1095. [PMID: 32978938 PMCID: PMC8355503 DOI: 10.1093/ibd/izaa250] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/20/2020] [Indexed: 12/09/2022]
Abstract
BACKGROUND Hypertrophy of visceral adipose tissue (VAT) is a hallmark of Crohn disease (CD). The VAT produces a wide range of adipokines, biologically active factors that contribute to metabolic disorders in addition to CD pathogenesis. The study aim was to concomitantly evaluate serum adipokine profiles and VAT volumes as predictors of disease outcomes and treatment course in newly diagnosed pediatric patients with CD. METHODS Pediatric patients ages 6 to 20 years were enrolled, and their clinical data and anthropometric measurements were obtained. Adipokine levels were measured at 0, 6, and 12 months after CD diagnosis and baseline in control patients (CP). The VAT volumes were measured by magnetic resonance imaging or computed tomography imaging within 3 months of diagnosis. RESULTS One hundred four patients undergoing colonoscopy were prospectively enrolled: 36 diagnosed with CD and 68 CP. The serum adipokine resistin and plasminogen activator inhibitor (PAI)-1 levels were significantly higher in patients with CD at diagnosis than in CP. The VAT volume was similar between CD and CP. Baseline resistin levels at the time of diagnosis in patients with CD who were escalated to biologics was significantly higher than in those not treated using biologic therapy by 12 months (29.8 ng/mL vs 13.8 ng/mL; P = 0.004). A resistin level of ≥29.8 ng/mL at the time of diagnosis predicted escalation to biologic therapy in the first year after diagnosis with a specificity of 95% (sensitivity = 53%; area under the curve = 0.82; P = 0.015 for model with log-scale). There was a significantly greater reduction in resistin (P = 0.002) and PAI-1 (P = 0.010) at the 12-month follow-up in patients on biologics compared with patients who were not treated using biologics. CONCLUSIONS Serum resistin levels at diagnosis of pediatric CD predict the escalation to biologic therapy at 12 months, independent of VAT volumes. Resistin and PAI-1 levels significantly improved in patients with CD after treatment using biologics compared with those not on biologics. These results suggest the utility of resistin as a predictive biomarker in pediatric CD.
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Affiliation(s)
- Jacob A Kurowski
- Pediatric Gastroenterology, Hepatology, and Nutrition, Cleveland Clinic, Cleveland, Ohio, United States,Address correspondence to: Jacob A. Kurowski, MD, Cleveland Clinic, Pediatric Gastroenterology, Hepatology, and Nutrition, 9500 Euclid Avenue, Desk R3, Cleveland, OH 44195 ()
| | - Jean-Paul Achkar
- Gastroenterology, Hepatology, and Nutrition, Cleveland Clinic, Cleveland, Ohio, United States
| | - Rishi Gupta
- Pediatric Gastroenterology, University of Rochester, Rochester, New York, United States
| | - Iulia Barbur
- Biomedical Engineering, Case Western Reserve University, Cleveland, Ohio, United States
| | - Tracey L Bonfield
- Pediatrics, Case Western Reserve University, Cleveland, Ohio, United States
| | - Sarah Worley
- Quantitative Health Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, United States
| | - Erick M Remer
- Imaging Institute, Cleveland Clinic, Cleveland, Ohio, United States
| | - Claudio Fiocchi
- Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, United States
| | - Satish E Viswanath
- Biomedical Engineering, Case Western Reserve University, Cleveland, Ohio, United States
| | - Marsha H Kay
- Pediatric Gastroenterology, Hepatology, and Nutrition, Cleveland Clinic, Cleveland, Ohio, United States
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Magnetic resonance imaging assessment of body composition parameters in Crohn's disease. Dig Liver Dis 2020; 52:878-884. [PMID: 32622612 DOI: 10.1016/j.dld.2020.06.024] [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] [Received: 12/09/2019] [Revised: 05/27/2020] [Accepted: 06/08/2020] [Indexed: 12/11/2022]
Abstract
BACKGROUND Body composition, currently evaluated by computed tomography scan, is related to poor evolution and severity of Crohn's disease (CD). Few MRI studies have been performed, yet it is the most commonly used imaging modality for the surveillance of the disease. AIM Evaluate the feasibility of MRI body composition measurement and compare the variation according to the activity of the disease. METHODS A cohort of 132 consecutive patients was studied. The visceral adiposity index (VAI), subcutaneous adiposity index (SAI) and skeletal muscle index (SMI) were measured. Patients were divided into 2 groups according to disease activity. Sarcopenic status was defined according to the cut off value (SMI < 38.9 cm2/m2 in women and < 54.4 cm2/m2 in men). RESULTS MRI measurements of body composition parameters were feasible and reproducible. After adjustment, sarcopenia was more common (2.07 [1.02; 4.27], p = 0.046), and the SMI (-4.90 [-9.36; -0.431], p = 0.032) was lower in active disease. The SAI was lower (-14.7 [-29.8; 0.258], p = 0.054) in active disease. The VAI tended to be higher with active disease (3.91 [-3.50; 11.9], p = 0.34), and the VAI/SAI+VAI ratio was higher (9.40 [4.72; 14.1], p<0.001). CONCLUSION Assessment of body composition is feasible and reproducible in routine MR and parameters are related to disease activity.
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Microbial Signature in Adipose Tissue of Crohn's Disease Patients. J Clin Med 2020; 9:jcm9082448. [PMID: 32751800 PMCID: PMC7465250 DOI: 10.3390/jcm9082448] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2020] [Revised: 07/28/2020] [Accepted: 07/29/2020] [Indexed: 02/08/2023] Open
Abstract
Crohn’s disease (CD) is characterized by compromised immune tolerance to the intestinal commensal microbiota, intestinal barrier inflammation, and hyperplasia of creeping fat (CF) and mesenteric adipose tissue (AT), which seems to be directly related to disease activity. Gut microbiota dysbiosis might be a determining factor in CD etiology, manifesting as a low microbial diversity and a high abundance of potentially pathogenic bacteria. We tested the hypothesis that CF is a reservoir of bacteria through 16S-rRNA sequencing of several AT depots of patients with active and inactive disease and controls. We found a microbiome signature within CF and mesenteric AT from patients, but not in subcutaneous fat. We failed to detect bacterial DNA in any fat depot of controls. Proteobacteria was the most abundant phylum in both CF and mesenteric AT, and positively correlated with fecal calprotectin/C-reactive protein. Notably, the clinical status of patients seemed to be related to the microbiome signature, as those with the inactive disease showed a reduction in the abundance of pathogenic bacteria. Predictive functional profiling revealed many metabolic pathways including lipopolysaccharide biosynthesis and sulfur metabolism overrepresented in active CD relative to that in inactive CD. Our findings demonstrate that microbiota dysbiosis associated with CD pathophysiology is reflected in AT and might contribute to disease severity.
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High circulating elafin levels are associated with Crohn's disease-associated intestinal strictures. PLoS One 2020; 15:e0231796. [PMID: 32287314 PMCID: PMC7156098 DOI: 10.1371/journal.pone.0231796] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2020] [Accepted: 03/31/2020] [Indexed: 12/22/2022] Open
Abstract
Background Antimicrobial peptide expression is associated with disease activity in inflammatory bowel disease (IBD) patients. IBD patients have abnormal expression of elafin, a human elastase-specific protease inhibitor and antimicrobial peptide. We determined elafin expression in blood, intestine, and mesenteric fat of IBD and non-IBD patients. Methods Serum samples from normal and IBD patients were collected from two UCLA cohorts. Surgical resection samples of human colonic and mesenteric fat tissues from IBD and non-IBD (colon cancer) patients were collected from Cedars-Sinai Medical Center. Results High serum elafin levels were associated with a significantly elevated risk of intestinal stricture in Crohn’s disease (CD) patients. Microsoft Azure Machine learning algorithm using serum elafin levels and clinical data identified stricturing CD patients with high accuracy. Serum elafin levels had weak positive correlations with clinical disease activity (Partial Mayo Score and Harvey Bradshaw Index), but not endoscopic disease activity (Mayo Endoscopic Subscore and Simple Endoscopic Index for CD) in IBD patients. Ulcerative colitis (UC) patients had high serum elafin levels. Colonic elafin mRNA and protein expression were not associated with clinical disease activity and histological injury in IBD patients, but stricturing CD patients had lower colonic elafin expression than non-stricturing CD patients. Mesenteric fat in stricturing CD patients had significantly increased elafin mRNA and protein expression, which may contribute to high circulating elafin levels. Human mesenteric fat adipocytes secrete elafin protein. Conclusions High circulating elafin levels are associated with the presence of stricture in CD patients. Serum elafin levels may help identify intestinal strictures in CD patients.
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Serena C, Millan M, Ejarque M, Saera-Vila A, Maymó-Masip E, Núñez-Roa C, Monfort-Ferré D, Terrón-Puig M, Bautista M, Menacho M, Martí M, Espin E, Vendrell J, Fernández-Veledo S. Adipose stem cells from patients with Crohn's disease show a distinctive DNA methylation pattern. Clin Epigenetics 2020; 12:53. [PMID: 32252817 PMCID: PMC7137346 DOI: 10.1186/s13148-020-00843-3] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2019] [Accepted: 03/24/2020] [Indexed: 12/22/2022] Open
Abstract
Background Crohn’s disease (CD) is characterized by persistent inflammation and ulceration of the small or large bowel, and expansion of mesenteric adipose tissue, termed creeping fat (CF). We previously demonstrated that human adipose-derived stem cells (hASCs) from CF of patients with CD exhibit dysfunctional phenotypes, including a pro-inflammatory profile, high phagocytic capacity, and weak immunosuppressive properties. Importantly, these phenotypes persist in patients in remission and are found in all adipose depots explored including subcutaneous fat. We hypothesized that changes in hASCs are a consequence of epigenetic modifications. Methods We applied epigenome-wide profiling with a methylation array (Illumina EPIC/850k array) and gene expression analysis to explore the impact of CD on the methylation signature of hASCs isolated from the subcutaneous fat of patients with CD and healthy controls (n = 7 and 5, respectively; cohort I). Differentially methylated positions (p value cutoff < 1 × 10−4 and ten or more DMPs per gene) and regions (inclusion threshold 0.2, p value cutoff < 1 × 10−2 and more than 2 DMRs per gene) were identified using dmpfinder and Bumphunter (minfi), respectively. Changes in the expression of differentially methylated genes in hASCs were validated in a second cohort (n = 10/10 inactive and active CD and 10 controls; including patients from cohort I) and also in peripheral blood mononuclear cells (PBMCs) of patients with active/inactive CD and of healthy controls (cohort III; n = 30 independent subjects). Results We found a distinct DNA methylation landscape in hASCs from patients with CD, leading to changes in the expression of differentially methylated genes involved in immune response, metabolic, cell differentiation, and development processes. Notably, the expression of several of these genes in hASCs and PBMCs such as tumor necrosis factor alpha (TNFA) and PR domain zinc finger protein 16 (PRDM16) were not restored to normal (healthy) levels after disease remission. Conclusions hASCs of patients with CD exhibit a unique DNA methylation and gene expression profile, but the expression of several genes are only partially restored in patients with inactive CD, both in hASCs and PBMCs. Understanding how CD shapes the functionality of hASCs is critical for investigating the complex pathophysiology of this disease, as well as for the success of cell-based therapies. Graphical abstract Human adipose-stem cells isolated from subcutaneous fat of patients with Crohn’s disease exhibit an altered DNA methylation pattern and gene expression profile compared with those isolated from healthy individuals, with immune system, cell differentiation, metabolic and development processes identified as the main pathways affected. Interestingly, the gene expression of several genes involved in these pathways is only partially restored to control levels in patients with inactive Crohn’s disease, both in human adipose-stem cells and peripheral blood mononuclear cells. Understanding how Crohn’s disease shapes the functionality of human adipose-stem cells is critical for investigating the complex pathophysiology of this disease, as well as for the success of cell-based therapies.
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Affiliation(s)
- Carolina Serena
- Institut d´Investigació Sanitària Pere Virgili, Hospital Universitari Joan XXIII, Dr Mallafré Guasch, 4, 43007, Tarragona, Spain.,CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III, 28014, Madrid, Spain
| | - Monica Millan
- Colorectal Surgery Unit, Hospital Universitari Joan XXIII, 43007, Tarragona, Spain.,Colorectal Surgery Unit, Hospital Universitari La Fe, Valencia, Spain
| | - Miriam Ejarque
- Institut d´Investigació Sanitària Pere Virgili, Hospital Universitari Joan XXIII, Dr Mallafré Guasch, 4, 43007, Tarragona, Spain.,CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III, 28014, Madrid, Spain
| | - Alfonso Saera-Vila
- Institut d´Investigació Sanitària Pere Virgili, Hospital Universitari Joan XXIII, Dr Mallafré Guasch, 4, 43007, Tarragona, Spain
| | - Elsa Maymó-Masip
- Institut d´Investigació Sanitària Pere Virgili, Hospital Universitari Joan XXIII, Dr Mallafré Guasch, 4, 43007, Tarragona, Spain.,CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III, 28014, Madrid, Spain
| | - Catalina Núñez-Roa
- Institut d´Investigació Sanitària Pere Virgili, Hospital Universitari Joan XXIII, Dr Mallafré Guasch, 4, 43007, Tarragona, Spain.,CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III, 28014, Madrid, Spain
| | - Diandra Monfort-Ferré
- Institut d´Investigació Sanitària Pere Virgili, Hospital Universitari Joan XXIII, Dr Mallafré Guasch, 4, 43007, Tarragona, Spain
| | - Margarida Terrón-Puig
- Institut d´Investigació Sanitària Pere Virgili, Hospital Universitari Joan XXIII, Dr Mallafré Guasch, 4, 43007, Tarragona, Spain.,CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III, 28014, Madrid, Spain
| | - Michelle Bautista
- Digestive Unit, Hospital Universitari Joan XXIII, 43007, Tarragona, Spain
| | - Margarita Menacho
- Digestive Unit, Hospital Universitari Joan XXIII, 43007, Tarragona, Spain
| | - Marc Martí
- Colorectal Surgery Unit, General Surgery Service, Hospital Valle de Hebron, Universitat Autonoma de Barcelona, 08035, Barcelona, Spain
| | - Eloy Espin
- Colorectal Surgery Unit, General Surgery Service, Hospital Valle de Hebron, Universitat Autonoma de Barcelona, 08035, Barcelona, Spain
| | - Joan Vendrell
- Institut d´Investigació Sanitària Pere Virgili, Hospital Universitari Joan XXIII, Dr Mallafré Guasch, 4, 43007, Tarragona, Spain. .,CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III, 28014, Madrid, Spain. .,Universitat Rovira i Virgili, Tarragona, Spain.
| | - Sonia Fernández-Veledo
- Institut d´Investigació Sanitària Pere Virgili, Hospital Universitari Joan XXIII, Dr Mallafré Guasch, 4, 43007, Tarragona, Spain. .,CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III, 28014, Madrid, Spain.
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Nutrition Assessment in Crohn’s Disease using Anthropometric, Biochemical, and Dietary Indexes: A Narrative Review. J Acad Nutr Diet 2020; 120:624-640. [DOI: 10.1016/j.jand.2019.04.013] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2018] [Revised: 04/10/2019] [Accepted: 04/17/2019] [Indexed: 12/25/2022]
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Clinical assessment of risk factors for infection in inflammatory bowel disease patients. Int J Colorectal Dis 2020; 35:491-500. [PMID: 31915983 DOI: 10.1007/s00384-019-03501-0] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 12/26/2019] [Indexed: 02/04/2023]
Abstract
PURPOSE Recognizing patients with inflammatory bowel disease who are prone to infection would enable the adjustment of the type and intensity of immunosuppressive treatment. The aim of this study was to identify a clinical profile of risk for infections in IBD patients, based on the interaction of immunosuppressive treatment with factors inherent to the patient. METHODS A case-control study was performed among patients older than 18 years. Patients with any significant infection (any kind of severe or recurrent infection according to standard clinical criteria or a critical enough infection according to the patient) were defined as cases. Both cases and controls were randomly selected in a 1:3 ratio. All the period from diagnosis to the end of recruitment (June 2016) was analyzed. Risk factors for infection were identified by logistic regression analysis; the strength of association was reported by odds ratio (OR) with 95% confidence interval (95%CI). RESULTS A total of 112 cases and 270 controls were included. The independent risk factors for significant infection are the number of immunosuppressants (one drug: OR 1.28, 95% CI 0.53-3.11, two drugs: OR 2.37, 95% CI 1.01-5,56, and three drugs: OR 5.84, 95% CI 1.57-21.72), body mass index (OR 1.08; 95 %CI 1,01-1,16), the degree of comorbidity (OR 1.52; 95% CI 1.04-2.21), and the intensity of inflammatory activity (OR 1.43; 95% CI 1.19-1.71). CONCLUSIONS Regardless of immunosuppression, several patient factors such as comorbidity, body mass index, or the inflammatory activity of the disease determine the individual risk of infectious complications and should be considered for an adequate risk assessment.
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