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Dolu S, Arayici ME, Onem S, Dongelli H, Akarsu M. Diagnostic and Clinical Impact of Double-Balloon Enteroscopy in Small-Bowel Inflammatory Lesions: A Retrospective Cohort Study in a Turkish Population. Diagnostics (Basel) 2025; 15:661. [PMID: 40150004 PMCID: PMC11941567 DOI: 10.3390/diagnostics15060661] [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: 02/20/2025] [Revised: 03/06/2025] [Accepted: 03/07/2025] [Indexed: 03/29/2025] Open
Abstract
Background/Objectives: Small-bowel inflammatory lesions are challenging to diagnose thanks to their anatomical complexity and the limitations of conventional imaging. Double-balloon enteroscopy (DBE) allows for direct visualization, biopsy, and therapeutic intervention. This study evaluated the diagnostic yield and clinical impact of DBE in small-bowel inflammatory lesions, particularly in differentiating Crohn's disease (CD) from other etiologies. Methods: This retrospective study included 258 patients who underwent DBE for suspected small-bowel inflammatory lesions at Dokuz Eylül University Hospital (2010-2024). Patients were categorized into the CD and non-CD groups. The clinical, radiological, and endoscopic findings were also analyzed. Statistical comparisons were performed to assess the differences in presentation and DBE findings between the groups. Results: The mean patient age was 48.2 ± 17.3 years. Abdominal pain (47.7%) and diarrhea (31.8%) were the most common symptoms. The DBE findings included ulcers (45.0%), superficial mucosal changes (23.3%), and strictures (9.7%). The ileum was the most commonly affected site (31.7%). CD was diagnosed in 27.5% of the patients, while other etiologies included non-steroidal anti-inflammatory drug-induced (NSAID) enteropathy (12.0%) and malignancies (15.9%). Ulcers were significantly more frequent in patients with CD than in those without (60.3% vs. 39.0%, p = 0.002). Conclusions: DBE plays a crucial role in diagnosing small-bowel inflammatory lesions, distinguishing CD from other conditions, and guiding clinical management. It remains essential for cases requiring histopathological confirmation, offering superior diagnostic accuracy compared to noninvasive imaging.
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Affiliation(s)
- Suleyman Dolu
- Department of Gastroenterology, Faculty of Medicine, Dokuz Eylul University, 15 July Medicine and Art Campus, Inciralti-Balcova, Izmir 35340, Turkey
| | - Mehmet Emin Arayici
- Department of Biostatistics and Medical Informatics, Faculty of Medicine, Dokuz Eylul University, Izmir 35340, Turkey;
- Department of Public Health, Faculty of Medicine, Dokuz Eylul University, Izmir 35340, Turkey
| | - Soner Onem
- Department of Gastroenterology, Samsun Training and Research Hospital, Samsun 55090, Turkey
| | - Huseyin Dongelli
- Department of Internal Medicine, Faculty of Medicine, Dokuz Eylul University, Izmir 35340, Turkey
| | - Mesut Akarsu
- Private Gastroenterology Clinic, Izmir 35000, Turkey
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Chan BS, Bosco AA, Buckley NA. Navigating methotrexate toxicity: Examining the therapeutic roles of folinic acid and glucarpidase. Br J Clin Pharmacol 2025; 91:628-635. [PMID: 38889902 PMCID: PMC11862796 DOI: 10.1111/bcp.16096] [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: 02/02/2024] [Revised: 04/01/2024] [Accepted: 04/04/2024] [Indexed: 06/20/2024] Open
Abstract
Methotrexate (MTX) toxicity varies depending on factors such as dosing frequency (acute or repeated), dosage (low or high) and the administration route (oral, parenteral or intrathecal). Renal impairment can trigger or exacerbate MTX toxicity. Acute oral low-dose MTX (LDMTX) overdoses seldom lead to toxicity due to the saturable maximal bioavailable dose, but toxicity risks increase with repeated low doses (>3 days), high-dose MTX (HDMTX) or intrathecal poisoning. Folinic acid shares MTX transporters in the gut and cells and bypasses the MTX-induced dihydrofolate reductase inhibition. The required folinic acid dosage differs for low-dose and high-dose MTX toxicities. Acute LDMTX poisoning rarely requires folinic acid, while chronic LDMTX poisoning needs low-dose folinic acid until cellular function is restored. In HDMTX toxicities, early intravenous folinic acid administration is recommended, with dose and duration being guided by MTX concentrations and clinical improvement. In intrathecal MTX poisoning, folinic acid should be administered intravenously. Glucarpidase, a recombinant bacterial enzyme, has a high affinity for MTX and folate analogues in the intravascular or intrathecal systems. It decreases serum MTX concentrations by 90%-95% within 15 min. Its primary indication is for intrathecal MTX poisoning. It is rarely indicated in HDMTX toxicity unless patients have renal injury. However, there is no literature evidence supporting its use in HDMTX poisoning. Its use is limited by its significant cost and lack of availability. Haemodialysis can be potentially useful for MTX removal in cases where glucarpidase is not available. Additionally, fluid hydration, renal support and urine alkalinization are important adjunctive therapies for managing MTX toxicities.
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Affiliation(s)
- Betty S. Chan
- School of MedicineUniversity of New South WalesSydneyNew South WalesAustralia
- Department of Clinical Toxicology, Department of Emergency MedicinePrince of Wales HospitalRandwickNew South WalesAustralia
| | - Annmarie A. Bosco
- Haematology DepartmentPrince of Wales HospitalRandwickNew South WalesAustralia
| | - Nicholas A. Buckley
- Faculty of Medicine and HealthUniversity of SydneySydneyNew South WalesAustralia
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Alghamdi A, Alahmari M, Aljohani K, Alanazi A, Al Ibrahim B, Alshowair M, Tawfik M, Alghamdi W, Alanazi S, Alzayed F, Alghamdi AS, Bawazir A, Alhamidi H. Prevalence and clinical implications of anti-drug antibody formation and serum drug levels among patients with IBD receiving anti-TNF therapy: A cross-sectional study. Saudi J Gastroenterol 2025; 31:82-92. [PMID: 39849820 DOI: 10.4103/sjg.sjg_245_24] [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: 07/08/2024] [Accepted: 12/09/2024] [Indexed: 01/25/2025] Open
Abstract
BACKGROUND The emergence of tumor necrosis factor inhibitors (anti-TNF) has considerably changed the management of inflammatory bowel disease (IBD) in patients who do not respond to traditional therapies. This study assesses the prevalence of anti-TNF drug levels (DLs) and antibodies (ATAbs) in patients with IBD in Saudi Arabia and explores their associations with IBD type and prior anti-TNF failure. METHODS This cross-sectional study included patients aged 14-75 years diagnosed with Crohn's disease (CD) or ulcerative colitis (UC), treated with anti-TNF medications at King Fahad Medical City over January 2016 to December 2022. Data were analyzed using descriptive statistics, Mann-Whitney U test, Kruskal-Wallis test, Pearson's Chi-squared test, and multinomial logistic regression. RESULTS Among 392 patients with IBD (median age, 31 years), 75.8% were diagnosed with CD and 24.2% with UC. Anti-TNF levels were subtherapeutic in 27.0% patients, therapeutic in 21.5%, and supratherapeutic in 51.5%. ATAbs were negative in 73.1% patients, weakly positive in 9.8%, and positive in 17.1%. Subtherapeutic anti-TNF levels were significantly associated with positive ATAbs ( P < 0.001). Prior anti-TNF therapy failure was observed in 37.2% cases, with 15.3% showing immunogenicity. No significant demographic differences were noted across ATAbs groups. CONCLUSION We highlight the prevalence of subtherapeutic and supratherapeutic anti-TNF levels among patients with IBD in Saudi Arabia and their association with ATAbs. The findings underscore the importance of monitoring anti-TNF DLs and ATAbs to optimize treatment outcomes in IBD management. Future research should focus on the longitudinal impact of these factors and explore genetic predictors of treatment response.
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Affiliation(s)
- Ahmed Alghamdi
- Department of Gastroenterology and Hepatology, King Fahad Medical City, Riyadh, Saudi Arabia
- Department of Internal Medicine, College of Medicine, Dar Al Uloom University, Riyadh, Saudi Arabia
| | - Mohammed Alahmari
- Department of Gastroenterology and Hepatology, King Fahad Medical City, Riyadh, Saudi Arabia
| | - Khulood Aljohani
- Department of Gastroenterology and Hepatology, King Fahad Medical City, Riyadh, Saudi Arabia
| | - Aisha Alanazi
- Department of Gastroenterology and Hepatology, King Fahad Medical City, Riyadh, Saudi Arabia
| | - Bashaar Al Ibrahim
- Department of Gastroenterology and Hepatology, King Fahad Medical City, Riyadh, Saudi Arabia
| | - Mishal Alshowair
- Department of Gastroenterology and Hepatology, King Fahad Medical City, Riyadh, Saudi Arabia
| | - Marwa Tawfik
- Department of Gastroenterology and Hepatology, King Fahad Medical City, Riyadh, Saudi Arabia
- Internal Medicine Department, Hepatobiliary Unit, Alexandria Faculty of Medicine, Alexandria University, Alexandria, Egypt
| | - Waleed Alghamdi
- Department of Internal Medicine, King Fahad Medical City, Riyadh, Saudi Arabia
| | - Salman Alanazi
- Department of Internal Medicine, King Fahad Medical City, Riyadh, Saudi Arabia
| | - Faisal Alzayed
- Department of Internal Medicine, King Fahad Medical City, Riyadh, Saudi Arabia
| | - Abdullah S Alghamdi
- Department of Gastroenterology and Hepatology, King Fahad Medical City, Riyadh, Saudi Arabia
| | - Abdullah Bawazir
- Department of Internal Medicine, King Fahad Medical City, Riyadh, Saudi Arabia
| | - Hussam Alhamidi
- Department of Gastroenterology and Hepatology, King Fahad Medical City, Riyadh, Saudi Arabia
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Soler-Silva A, Sánchez-Guillén L, Blanco-Antona F, Barber X, Millán M. Patterns and predictors of postoperative complications and recurrence after ileocecal resection for Crohn's disease: a national multicenter longitudinal study. Tech Coloproctol 2025; 29:61. [PMID: 39921815 DOI: 10.1007/s10151-024-03054-7] [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: 08/04/2024] [Accepted: 11/06/2024] [Indexed: 02/10/2025]
Abstract
BACKGROUND Crohn's disease (CD) negatively impacts quality of life, and a high percentage of patients will need surgery. Ileocecal resection (ICR) is the most common abdominal procedure performed in CD. Postoperative complications are frequent, and recurrence is common. The main objectives of this study were to analyze risk factors (RF) for anastomotic leakage (AL) and recurrence after ICR, as well as quality of life (QoL) in CD in a sample of the Spanish population. METHODS A prospective, multicenter, observational study was designed, including all types of hospitals in Spain from 2018 to 2021. Demographic and medical-surgical characteristics, postoperative complications, hospital types by annual ICR volume, and quality of life (IBDQ-9) up to 1 year follow-up (OYF) were recorded and analyzed. RESULTS A total of 386 ICRs were recorded. At 60 days, there were 134 (36.4%) complications, 46 (11.91%) of which were major. A total of 23 (5.9%) AL were registered, and RF were Montreal A3 [OR 14.2, 95% CI (2.70-126), p = 0.005], Montreal p [OR 7.29, 95% CI (1.14-44.4), p = 0.029], and intensified adalimumab treatment [3.8, 95% CI (1.2-13.1), p = 0.026]. Recurrences at OYF were 67 (19%), and RF were history of neoplasia [OR 7.14, p = 0.01], Montreal B3 [OR 2.12, p = 0.02], and minimally invasive surgery (MIS) [OR 2.63, p = 0.02]. The mean difference in IBDQ-9 from baseline to 60 days was +1.72 (n = 177, p < 0.001) and to OYF +2.12 (n = 140, p < 0.001). CONCLUSIONS The AL rate was 5.9%. Montreal A3, perianal disease, and intensified adalimumab were associated with a higher rate of AL. The recurrence rate was 17.6% (OYF). Prior neoplasia, Montreal B3, and MIS were associated with higher risk of recurrence. ICR improves quality of life at 60 days and is maintained 1 year after surgery.
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Affiliation(s)
| | - L Sánchez-Guillén
- Elche University General Hospital, Elche, Spain.
- Miguel Hernández University of Elche ES, Salamanca, Spain.
| | - F Blanco-Antona
- Complejo Hospitalario de Salamanca, University of Salamanca, Salamanca, Spain
| | - X Barber
- Miguel Hernández University of Elche ES, Salamanca, Spain
- Center of Operation Research (CIO), Department of Statistics, Mathematics and Information Technology, Universidad Miguel Hernández de Elche, Elche, Spain
| | - M Millán
- Hospital Universitari i Politècnic La Fe, Valencia, Spain
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5
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Vieujean S, Jairath V, Peyrin-Biroulet L, Dubinsky M, Iacucci M, Magro F, Danese S. Understanding the therapeutic toolkit for inflammatory bowel disease. Nat Rev Gastroenterol Hepatol 2025:10.1038/s41575-024-01035-7. [PMID: 39891014 DOI: 10.1038/s41575-024-01035-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 12/19/2024] [Indexed: 02/03/2025]
Abstract
Inflammatory bowel disease (IBD), encompassing ulcerative colitis and Crohn's disease, is a group of chronic, immune-mediated disorders of the gastrointestinal tract that present substantial clinical challenges owing to their complex pathophysiology and tendency to relapse. A treat-to-target approach is recommended, involving iterative treatment adjustments to achieve clinical response, reduce inflammatory markers and achieve long-term goals such as mucosal healing. Lifelong medication is often necessary to manage the disease, maintain remission and prevent complications. The therapeutic landscape for IBD has evolved substantially; however, a ceiling on therapeutic efficacy remains and surgery is sometimes required (owing to uncontrolled disease activity or complications). Effective IBD management involves comprehensive care, including medication adherence and a collaborative clinician-patient relationship. This Review discusses current therapeutic options for IBD, detailing mechanisms of action, efficacy, safety profiles and guidelines for use of each drug class. We also explore emerging therapies and the role of surgery. Additionally, the importance of a multidisciplinary team and personalized care in managing IBD is emphasized, advocating for patient empowerment and involvement in treatment decisions. By synthesizing current knowledge and emerging trends, this Review aims to equip healthcare professionals with a thorough understanding of therapeutic options for IBD, enhancing informed, evidence-based decisions in clinical practice.
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Affiliation(s)
- Sophie Vieujean
- Hepato-Gastroenterology and Digestive Oncology, University Hospital CHU of Liège, Liège, Belgium
- Department of Gastroenterology, INFINY Institute, CHRU Nancy, Vandœuvre-lès-Nancy, France
| | - Vipul Jairath
- Division of Gastroenterology, Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada
| | - Laurent Peyrin-Biroulet
- Department of Gastroenterology, INFINY Institute, CHRU Nancy, Vandœuvre-lès-Nancy, France
- Division of Gastroenterology and Hepatology, McGill University Health Centre, Montreal, Quebec, Canada
| | - Marla Dubinsky
- Department of Paediatrics, Susan and Leonard Feinstein IBD Center, Icahn School of Medicine, Mount Sinai, New York, NY, USA
| | - Marietta Iacucci
- APC Microbiome Ireland, College of Medicine and Health, University College of Cork, Cork, Ireland
| | - Fernando Magro
- CINTESIS@RISE, Faculty of Medicine, University of Porto, Porto, Portugal
| | - Silvio Danese
- Gastroenterology and Endoscopy, IRCCS Ospedale San Raffaele and University Vita-Salute San Raffaele, Milano, Italy.
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Abhishek A, Nakafero G, Card T, Taal MW, Grainge MJ, Aithal GP, Mallen CD, Stevenson MD, Riley RD. Monitoring for 5-aminosalicylate nephrotoxicity in adults with inflammatory bowel disease: prognostic model development and validation using data from the Clinical Practice Research Datalink. BMJ Open Gastroenterol 2025; 12:e001627. [PMID: 39863289 PMCID: PMC11784381 DOI: 10.1136/bmjgast-2024-001627] [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: 10/08/2024] [Accepted: 01/07/2025] [Indexed: 01/27/2025] Open
Abstract
OBJECTIVE To develop and validate a prognostic model for risk-stratified monitoring of 5-aminosalicylate nephrotoxicity. METHODS This UK retrospective cohort study used data from the Clinical Practice Research Datalink Aurum and Gold for model development and validation respectively. It included adults newly diagnosed with inflammatory bowel disease and established on 5-aminosalicylic acid (5-ASA) treatment between 1 January 2007 and 31 December 2019. Drug discontinuation associated with 5-ASA nephrotoxicity defined as a prescription gap of ≥90 days with decline in kidney function was the outcome. Patients prescribed 5-ASAs for ≥6 months were followed-up for up to 5 years. Penalised Cox regression was used to develop the risk equation with bootstrapping for internal validation and optimism adjustment. Model performance was assessed in terms of calibration and discrimination. RESULTS 13 728 and 7318 participants who contributed 40 378 and 20 679 person-years follow-up formed the development and validation cohorts with 170 (1.2%) and 98 (1.3%) outcome events respectively. Nine predictors were included in the final model, including chronic kidney disease stage 3 and hazardous alcohol use as strong predictors. Age and Body Mass Index were weak predictors. The optimism-adjusted calibration slope, C and D statistics in the development and validation data were 0.90, 0.64 and 0.98, and 1.01, 0.66 and 0.94 respectively. CONCLUSION This prognostic model used information from routine clinical care and performed well in an independent validation cohort. It can be used to risk-stratify blood test monitoring during established 5-ASA treatment. A key limitation is that the decline in kidney function could have been due to factors other than 5-ASA nephrotoxicity.
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Affiliation(s)
- Abhishek Abhishek
- Academic Rheumatology, University of Nottingham, Nottingham, East Midlands, UK
- Nottingham NIHR BRC, Nottingham, UK
| | - Georgina Nakafero
- Academic Rheumatology, University of Nottingham, Nottingham, East Midlands, UK
- Nottingham NIHR BRC, Nottingham, UK
| | - Tim Card
- Lifespan and Population Health, School of Medicine, University of Nottingham, Nottingham, UK
| | - Maarten W Taal
- Centre for Kidney Research and Innovation, Translational Medical Sciences, University of Nottingham, Nottingham, UK
| | - Matthew J Grainge
- Lifespan and Population Health, School of Medicine, University of Nottingham, Nottingham, UK
| | - Guruprasad P Aithal
- Nottingham NIHR BRC, Nottingham, UK
- Nottingham Digestive Diseases Centre, Translational Medical Sciences, School of Medicine, University of Nottingham, Nottingham, UK
| | | | - Matthew D Stevenson
- School of Health and Related Research, University of Sheffield, Sheffield, UK
| | - Richard D Riley
- Institute of Applied Health Research, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK
- NIHR, Birmingham Biomedical Research Centre, Birmingham, UK
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Wu TH, Brandt CF, Scheike T, Burisch J, Jeppesen PB. The Natural History of Crohn's Disease Leading to Intestinal Failure: A Longitudinal Cohort Study from 1973 to 2018. J Crohns Colitis 2025; 19:jjae114. [PMID: 39039902 DOI: 10.1093/ecco-jcc/jjae114] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/20/2024] [Indexed: 07/24/2024]
Abstract
BACKGROUND AND AIMS The natural history of Crohn's disease leading to intestinal failure is not well characterised. This study aims to describe the clinical course of Crohn's disease preceding intestinal failure and to compare disease course and burden between Crohn's disease patients with and without intestinal failure. METHODS Patients with Crohn's disease complicated by intestinal failure from Rigshospitalet, Copenhagen [n = 182] and a nationwide Danish Crohn's disease cohort without intestinal failure [n = 22,845] were included. Using nationwide registries in Denmark, disease course was determined from hospitalisations, surgeries, and outpatient medications, and disease burden was determined from employment and mortality data. RESULTS The 10-year cumulative incidence of intestinal failure following Crohn's disease diagnosis declined from 2.7% prior to 1980 to 0.2% after 2000. Compared with Crohn's disease patients without intestinal failure, those with intestinal failure experienced significantly longer duration of severe disease [50 vs 19 years per 100 patient-years, p < 0.01], secondary to greater corticosteroid use [71% vs 60%, p = 0.02], inpatient contacts [98% vs 55%, p < 0.01], and abdominal surgeries [99% vs 48%, p < 0.01]. However, exposure to biologics was not different between the two groups [20.4% vs 21%, p = 0.95], and duration on biologics was shorter in Crohn's disease patients with intestinal failure [2068 vs 4126 days per 100 patient-years, p = 0.02]. Standard mortality ratio in Crohn's disease patients with intestinal failure was 3.66 (97.5% confidence interval [CI] 2.79, 4.72]. CONCLUSION Patients with Crohn's disease complicated by intestinal failure experienced a more persistently severe preceding course of Crohn's disease but were not more likely to be treated with biological therapy.
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Affiliation(s)
- Tian Hong Wu
- Department of Intestinal Failure and Liver Diseases, Rigshospitalet, Copenhagen, Denmark
| | | | - Thomas Scheike
- Department of Public Health, Section of Biostatistics, University of Copenhagen, Copenhagen, Denmark
| | - Johan Burisch
- Copenhagen Center for Inflammatory Bowel Disease in Children, Adolescents and Adults, Copenhagen University Hospital - Amager and Hvidovre, Hvidovre, Denmark
- Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark
| | - Palle Bekker Jeppesen
- Department of Intestinal Failure and Liver Diseases, Rigshospitalet, Copenhagen, Denmark
- Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark
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Fischer A, Mac S, Freiman ES, Marshall JK, Rand K, Ramos-Goñi JM. Cost Effectiveness of Sequencing Vedolizumab as First-Line Biologic in Ulcerative Colitis and Crohn's Disease in Canada: An Analysis Using Real-World Evidence from the EVOLVE Study. PHARMACOECONOMICS - OPEN 2025; 9:41-56. [PMID: 39377864 PMCID: PMC11718032 DOI: 10.1007/s41669-024-00523-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Accepted: 08/22/2024] [Indexed: 10/09/2024]
Abstract
INTRODUCTION Vedolizumab is a gut-selective anti-lymphocyte trafficking biologic indicated for the treatment of adult patients with moderately to severely active ulcerative colitis (UC) and Crohn's disease (CD) in Canada. OBJECTIVE The objective of this study was to evaluate the cost effectiveness of treatment sequencing for UC and CD from a public healthcare payer perspective, leveraging new real-world evidence from the literature and the EVOLVE study, a retrospective chart review. METHODS Using separate decision tree/Markov models to assess cost effectiveness for UC and CD, two sequencing approaches were estimated for adult patients (≥ 18 years) diagnosed with UC or CD who were biologic-naïve: vedolizumab as first-line biologic followed by anti-tumor necrosis factor (TNF)-α versus first-line anti-TNFα followed by vedolizumab. Treatment effectiveness (response and remission), surgery rates, dose escalation and regain of response and safety inputs were estimated from EVOLVE, a retrospective chart review of real-world data, and evidence synthesis from the literature, whereas costs and utilities were estimated from health technology assessment reports, clinical trials, and the literature. Biosimilar costs were used for anti-TNFα. Both models simulated a 5-year time horizon and discounted costs and outcomes at 1.5%. Probabilistic base-case analyses (n = 10,000) reported total costs (2023 Canadian dollars) and quality-adjusted life-years (QALYs). Several scenario analyses were conducted to explore robustness of results. RESULTS In UC, vedolizumab as a first-line biologic followed by anti-TNFα resulted in an incremental gain of 0.09 QALYs (2.46 vs. 2.55) and saved $7179 ($134,028 vs. $126,848), making this a dominant strategy compared with first-line anti-TNFα followed by vedolizumab. In CD, use of vedolizumab as a first-line biologic resulted in an incremental gain of 0.04 QALYs (3.35 vs. 3.39) at an incremental cost of $50,631 ($89,850 vs. $140,381) versus first-line anti-TNFα followed by vedolizumab (incremental cost-effectiveness ratio of $1,265,775 per QALY). CONCLUSIONS Based on this analysis, sequencing vedolizumab as a first-line biologic prior to anti-TNFα in UC and CD provided additional clinical benefit to patients. In UC, vedolizumab as a first-line biologic also saved healthcare system costs compared with anti-TNFα, whereas in CD, vedolizumab provided incremental benefit at an incremental cost, which was not considered cost effective at a threshold of $50,000/QALY.
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Affiliation(s)
- Aren Fischer
- Takeda Canada Inc., Toronto, ON, Canada
- Alexion Pharmaceuticals, Mississauga, ON, Canada
| | | | | | - John K Marshall
- Department of Medicine (Division of Gastroenterology) and Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, ON, Canada
| | - Kim Rand
- Maths in Health B.V., Amsterdam, The Netherlands
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Kameli N, Becker HEF, Jonkers DM, Penders J, Savelkoul P, Stassen F. Investigating the Immunomodulatory Impact of Fecal Bacterial Membrane Vesicles and Their IgA Coating Patterns in Crohn's Disease Patients. Int J Mol Sci 2024; 25:13194. [PMID: 39684904 DOI: 10.3390/ijms252313194] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2024] [Revised: 11/20/2024] [Accepted: 11/22/2024] [Indexed: 12/18/2024] Open
Abstract
The human intestinal tract contains trillions of bacteria that coexist in a symbiotic relationship with human cells. Imbalances in this interaction can lead to disorders such as Crohn's disease (CD). Bacteria membrane vesicles (MVs), which are released by almost all bacteria, have been demonstrated to play a crucial role in bacteria-host interactions. In this study, we assessed the physical characterizations, immunomodulatory effects, and IgA interactions of MVs derived from fecal samples of CD patients and healthy controls (HCs). MVs were isolated from the frozen fecal samples using a combination of ultrafiltration and size-exclusion chromatography. Using nanoparticle tracking analysis, we found that the MVs of the CD patients showed a significantly lower concentration compared to those of the HCs. Cryo-transmission electron microscopy revealed the larger size of the MVs in active CD (Ac-CD) compared to the MVs of remission CD (Re-CD) and HCs. Differentiated monocyte THP-1 cells released more TNF-a when exposed to MVs from the HCs compared to the CD patients. On the other hand, the MVs from the HCs and Re-CD patients but not the Ac-CD patients induced more anti-inflammatory IL-10. Intriguingly, bead-based flow cytometry analysis showed that the MVs of the HCs and Re-CD patients were more coated with IgA compared to those of the Ac-CD patients. These results suggest the potential role of MVs in the immunomodulatory impact on the pathophysiology of CD. Moreover, IgA seems to regulate these effects by direct binding, which was not the case for the Ac-CD patients. Finally, the IgA coating patterns of the MVs could be used as an additional disease biomarker, as they can clearly identify the exacerbation status of CD.
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Affiliation(s)
- Nader Kameli
- Department of Medical Microbiology, College of Nursing and Health Sciences, Jazan University, Jazan 6809, Saudi Arabia
- Health Research Center, Jazan Univesiry, Jazan 6809, Saudi Arabia
- Department of Medical Microbiology, Institute of Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University Medical Center+, 6229 HX Maastricht, The Netherlands
| | - Heike E F Becker
- Department of Medical Microbiology, Institute of Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University Medical Center+, 6229 HX Maastricht, The Netherlands
- Department of Gastroenterology/Hepatology, Institute of Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University Medical Center+, 6229 HX Maastricht, The Netherlands
| | - Daisy M Jonkers
- Department of Gastroenterology/Hepatology, Institute of Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University Medical Center+, 6229 HX Maastricht, The Netherlands
| | - John Penders
- Department of Medical Microbiology, Institute of Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University Medical Center+, 6229 HX Maastricht, The Netherlands
| | - Paul Savelkoul
- Department of Medical Microbiology, Institute of Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University Medical Center+, 6229 HX Maastricht, The Netherlands
- Department of Medical Microbiology and Infection Control, VU University Medical Center, 1081 HV Amsterdam, The Netherlands
| | - Frank Stassen
- Department of Gastroenterology/Hepatology, Institute of Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University Medical Center+, 6229 HX Maastricht, The Netherlands
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Cavalcanti E, Marra A, Mileti A, Donghia R, Curlo M, Mastronardi M. Nutritional Management in Stricturing Crohn's Disease: A Pilot Study. Nutrients 2024; 16:4153. [PMID: 39683547 PMCID: PMC11644502 DOI: 10.3390/nu16234153] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2024] [Revised: 11/20/2024] [Accepted: 11/29/2024] [Indexed: 12/18/2024] Open
Abstract
BACKGROUND More than half of patients with Crohn's disease develop intestinal fibrosis induced intestinal obstruction with debilitating symptoms throughout their disease course. The incidence of stricture formation in CD has remained unchanged over the last several decades. Factors promoting intestinal fibrosis are currently unclear, but diet may represent an underestimated risk factor for intestinal fibrosis by modification of both the host immune response and intestinal microbial composition. Evaluating the impact of diet on the course of IBD is very complex. Sarcopenia is a common problem in IBD patients and correlates with an increased rate of disease. Skeletal muscle index (SMI) is an important parameter to measure sarcopenia and is an easily accessible tool for evaluating the likelihood of complications in individuals with CD. METHODS Using a randomized and controlled pilot design, we aimed to investigate the efficacy of 12 months of short-term dietary intervention based on essential amino acid (EAA) and sodium butyrate (NaB) supplementation in the management of stricturing Crohn's disease patients. RESULTS After the treatment in the diet EAA/NaB group, we revealed a statistically significant improvement of muscle mass (61.49 ± 5.47 vs. control 86 ± 10.70, p = 0.01) and SMI index (9.97 ± 1.79 vs. control 7.60 ± 2.29, p = 0.02). In addition, the measurement of skeletal muscle mass in CD patients has been suggested to be crucial for predicting the disease course. Indeed, after one year, surgery was required in 4/10 control group patients (40%) and 1/10 study group (10%) patients, underlining the importance of body composition alterations and adequate dietary intake in the management of these patients. CONCLUSIONS Further prospective studies are needed to confirm these results; nonetheless this nutritional approach could become an integral part in the treatment of stricturing CD patients to improve disease outcomes and increase the quality of life in these patients.
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Affiliation(s)
- Elisabetta Cavalcanti
- IBD Unit, National Institute of Gastroenterology-IRCCS, 70013 Castellana Grotte, Italy; (A.M.); (A.M.); (M.C.); (M.M.)
| | - Antonella Marra
- IBD Unit, National Institute of Gastroenterology-IRCCS, 70013 Castellana Grotte, Italy; (A.M.); (A.M.); (M.C.); (M.M.)
| | - Alessia Mileti
- IBD Unit, National Institute of Gastroenterology-IRCCS, 70013 Castellana Grotte, Italy; (A.M.); (A.M.); (M.C.); (M.M.)
| | - Rossella Donghia
- Data Science Unit, National Institute of Gastroenterology-IRCCS, 70013 Castellana Grotte, Italy;
| | - Margherita Curlo
- IBD Unit, National Institute of Gastroenterology-IRCCS, 70013 Castellana Grotte, Italy; (A.M.); (A.M.); (M.C.); (M.M.)
| | - Mauro Mastronardi
- IBD Unit, National Institute of Gastroenterology-IRCCS, 70013 Castellana Grotte, Italy; (A.M.); (A.M.); (M.C.); (M.M.)
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Matsumoto H, Sasahira M, Go TT, Yo S, Ninomiya T, Osawa M, Handa O, Umegami E, Inoue R, Shiotani A. Characteristics of Mucosa-Associated Microbiota in Ulcerative Colitis Patients with 5-Aminosalicylic Acid Intolerance. Biomedicines 2024; 12:2125. [PMID: 39335641 PMCID: PMC11428711 DOI: 10.3390/biomedicines12092125] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2024] [Revised: 09/15/2024] [Accepted: 09/16/2024] [Indexed: 09/30/2024] Open
Abstract
BACKGROUND/OBJECTIVES 5-Aminosalicylic acid (5-ASA) is a first-line therapy for ulcerative colitis (UC). This study examined the mucosa-associated microbiota (MAM) in UC patients, distinguishing between those who were 5-ASA tolerant and intolerant. METHODS Brushing samples were collected from the sigmoid and ileal end of patients with UC during endoscopic procedures. The samples were profiled by using the Illumina MiSeq platform. The V3-V4 regions of the 16S rRNA gene (460 bp) were amplified by using tailed PCR. RESULTS A total of 15 patients with 5-ASA intolerance, 38 patients with 5-ASA tolerance, and 19 healthy controls were recruited in this study. The α-diversity indices were remarkably different among the three groups in the ileum mucosa but not in the sigmoid colon. In the ileum mucosa, Alistipes, Ruminococcaceae, and Odoribacter were less abundant in the 5-ASA-intolerant group than in the control and 5-ASA-tolerant groups. On the contrary, Merdibacter, Brevundimonas, and Porphyromonas were more abundant in the 5-ASA-intolerant group than in other groups. CONCLUSIONS The present study showed that the changes in MAM were characterized by a decrease in mucoprotective bacteria rather than an increase in harmful bacteria.
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Affiliation(s)
- Hiroshi Matsumoto
- Department of Gastroenterology, Kawasaki Medical School, Okayama 701-0192, Japan; (M.S.); (T.T.G.); (S.Y.); (T.N.); (M.O.); (O.H.); (E.U.); (A.S.)
| | - Momoyo Sasahira
- Department of Gastroenterology, Kawasaki Medical School, Okayama 701-0192, Japan; (M.S.); (T.T.G.); (S.Y.); (T.N.); (M.O.); (O.H.); (E.U.); (A.S.)
| | - Tei Tei Go
- Department of Gastroenterology, Kawasaki Medical School, Okayama 701-0192, Japan; (M.S.); (T.T.G.); (S.Y.); (T.N.); (M.O.); (O.H.); (E.U.); (A.S.)
| | - Shogen Yo
- Department of Gastroenterology, Kawasaki Medical School, Okayama 701-0192, Japan; (M.S.); (T.T.G.); (S.Y.); (T.N.); (M.O.); (O.H.); (E.U.); (A.S.)
| | - Takehiro Ninomiya
- Department of Gastroenterology, Kawasaki Medical School, Okayama 701-0192, Japan; (M.S.); (T.T.G.); (S.Y.); (T.N.); (M.O.); (O.H.); (E.U.); (A.S.)
| | - Motoyasu Osawa
- Department of Gastroenterology, Kawasaki Medical School, Okayama 701-0192, Japan; (M.S.); (T.T.G.); (S.Y.); (T.N.); (M.O.); (O.H.); (E.U.); (A.S.)
| | - Osamu Handa
- Department of Gastroenterology, Kawasaki Medical School, Okayama 701-0192, Japan; (M.S.); (T.T.G.); (S.Y.); (T.N.); (M.O.); (O.H.); (E.U.); (A.S.)
| | - Eiji Umegami
- Department of Gastroenterology, Kawasaki Medical School, Okayama 701-0192, Japan; (M.S.); (T.T.G.); (S.Y.); (T.N.); (M.O.); (O.H.); (E.U.); (A.S.)
| | - Ryo Inoue
- Faculty of Agriculture, Setsunan University, 45-1 Nagaotoge-cho, Hirakata 573-0101, Japan;
| | - Akiko Shiotani
- Department of Gastroenterology, Kawasaki Medical School, Okayama 701-0192, Japan; (M.S.); (T.T.G.); (S.Y.); (T.N.); (M.O.); (O.H.); (E.U.); (A.S.)
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12
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Angriman I, Sampietro GM. Ileocaecal Crohn's disease. To resect or not to resect, is that the question? Dig Liver Dis 2024; 56:1298-1300. [PMID: 38734567 DOI: 10.1016/j.dld.2024.04.029] [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: 04/24/2024] [Accepted: 04/26/2024] [Indexed: 05/13/2024]
Affiliation(s)
- Imerio Angriman
- General Surgery Unit 3, Padua University Hospital, Padua, Italy
| | - Gianluca M Sampietro
- Division of General and HPB Surgery, Rho Memorial Hospital, ASST Rhodense, Rho Milano, Italy.
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Cicerone C, D’Amico F, Allocca M, Zilli A, Parigi TL, Danese S, Furfaro F. A Comprehensive Multidisciplinary Approach to Diagnosing Chronic Inflammatory Bowel Diseases: Integration of Clinical, Endoscopic, and Imaging Modalities. Diagnostics (Basel) 2024; 14:1530. [PMID: 39061667 PMCID: PMC11275644 DOI: 10.3390/diagnostics14141530] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2024] [Revised: 07/12/2024] [Accepted: 07/13/2024] [Indexed: 07/28/2024] Open
Abstract
Chronic inflammatory bowel diseases, such as Crohn's disease and ulcerative colitis, present diagnostic challenges due to their complex and heterogeneous nature. While histology remains fundamental for accurate diagnosis, a multidisciplinary approach incorporating clinical, endoscopic, and imaging modalities is increasingly recognized as essential for comprehensive evaluation. This article delves into the importance of integrating various diagnostic techniques in the assessment of IBD. Colonoscopy and histology, with its ability to directly visualize the intestinal mucosa, play a central role in the diagnostic process. However, histological analysis alone may not suffice, necessitating the inclusion of advanced imaging techniques, such as magnetic resonance enterography (MRE), computed tomography enterography (CTE), and intestinal ultrasound (IUS). These techniques provide valuable insights into the disease's extent, severity, and complications, and should be used in conjunction with biochemical parameters. These modalities complement traditional endoscopic and histological findings, offering a more holistic understanding of the disease process. A multidisciplinary approach that incorporates clinical, endoscopic, histological, serological, and imaging assessments enables clinicians to achieve a more accurate and timely diagnosis of IBD. Moreover, this integrated approach facilitates personalized treatment strategies tailored to individual patient needs, ultimately improving clinical outcomes and quality of life for those affected by chronic inflammatory bowel diseases.
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Affiliation(s)
- Clelia Cicerone
- Department of Gastroenterology and Endoscopy, IRCCS San Raffaele Hospital, 20132 Milan, Italy; (C.C.); (F.D.); (M.A.); (A.Z.); (T.L.P.); (S.D.)
| | - Ferdinando D’Amico
- Department of Gastroenterology and Endoscopy, IRCCS San Raffaele Hospital, 20132 Milan, Italy; (C.C.); (F.D.); (M.A.); (A.Z.); (T.L.P.); (S.D.)
| | - Mariangela Allocca
- Department of Gastroenterology and Endoscopy, IRCCS San Raffaele Hospital, 20132 Milan, Italy; (C.C.); (F.D.); (M.A.); (A.Z.); (T.L.P.); (S.D.)
| | - Alessandra Zilli
- Department of Gastroenterology and Endoscopy, IRCCS San Raffaele Hospital, 20132 Milan, Italy; (C.C.); (F.D.); (M.A.); (A.Z.); (T.L.P.); (S.D.)
| | - Tommaso Lorenzo Parigi
- Department of Gastroenterology and Endoscopy, IRCCS San Raffaele Hospital, 20132 Milan, Italy; (C.C.); (F.D.); (M.A.); (A.Z.); (T.L.P.); (S.D.)
- Department of Gastroenterology and Endoscopy, Vita-Salute San Raffaele University, 20132 Milan, Italy
| | - Silvio Danese
- Department of Gastroenterology and Endoscopy, IRCCS San Raffaele Hospital, 20132 Milan, Italy; (C.C.); (F.D.); (M.A.); (A.Z.); (T.L.P.); (S.D.)
- Department of Gastroenterology and Endoscopy, Vita-Salute San Raffaele University, 20132 Milan, Italy
| | - Federica Furfaro
- Department of Gastroenterology and Endoscopy, IRCCS San Raffaele Hospital, 20132 Milan, Italy; (C.C.); (F.D.); (M.A.); (A.Z.); (T.L.P.); (S.D.)
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14
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Ozturk O, Celebi G, Duman UG, Kupcuk E, Uyanik M, Sertoglu E. Short-chain fatty acid levels in stools of patients with inflammatory bowel disease are lower than those in healthy subjects. Eur J Gastroenterol Hepatol 2024; 36:890-896. [PMID: 38829943 DOI: 10.1097/meg.0000000000002789] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 06/05/2024]
Abstract
OBJECTIVE Short-chain fatty acids (SCFAs) are produced when the microbiota in the large intestine cause fermentation of dietary carbohydrates and fibers. These fatty acids constitute the primary energy source of colon mucosa cells and have a protective effect in patients suffering from inflammatory bowel disease (IBD). This study aimed to compare the SCFA levels in the stools of patients with IBD and healthy controls. METHOD Healthy controls and patients with IBD aged 18 and over were included in the study. Stool samples from all patients and healthy controls were collected, and stool acetic acid, propionic acid, and butyric acid levels were measured using a gas chromatography-mass spectrometry measurement method. RESULTS In this study, 64 participants were divided into two groups: 34 were in IBD (Crohn disease and ulcerative colitis) and 30 were in healthy control group. When fecal SCFA concentrations of IBD and healthy control groups were compared, a statistically significant difference was observed between them. When the fecal SCFA concentrations of Crohn's disease and ulcerative colitis patients in the IBD group were compared, however, no statistically significant difference was observed between them. Furthermore, when the participants' diet type (carbohydrate-based, vegetable-protein-based and mixed diet) and the number of meals were compared with fecal SCFA concentrations, no statistically significant difference was observed between them. CONCLUSION In general, fecal SCFA levels in patients with IBD were lower than those in healthy controls. Moreover, diet type and the number of meals had no effect on stool SCFA levels in patients with IBD and healthy individuals.
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Affiliation(s)
| | - Gurkan Celebi
- Department of Gastroenterology, Gulhane School of Medicine, University of Health Sciences, Ankara
| | | | | | - Metin Uyanik
- Department of Biochemistry, Çorlu State Hospital, Tekirdag, Turkey
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15
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Jarmakiewicz-Czaja S, Gruszecka J, Filip R. The Diagnosis of Intestinal Fibrosis in Crohn's Disease-Present and Future. Int J Mol Sci 2024; 25:6935. [PMID: 39000043 PMCID: PMC11241173 DOI: 10.3390/ijms25136935] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2024] [Revised: 06/17/2024] [Accepted: 06/20/2024] [Indexed: 07/14/2024] Open
Abstract
Crohn's disease (CD) progresses with periods of remission and exacerbations. During exacerbations, chronic inflammation leads to tissue destruction. As a result, intestinal fibrosis may develop in response to the ongoing inflammatory process. Fibrosis in CD should be considered the result of the response of the intestinal wall (over) to the presence of inflammation in the deep structures of the intestinal wall. In the absence of ideal noninvasive methods, endoscopic evaluation in combination with biopsy, histopathological analysis, stool analysis, and blood analysis remains the gold standard for assessing both inflammation and fibrosis in CD. On the contrary, the ability to identify markers of intestinal fibrosis would help to develop new diagnostic and therapeutic methods to detect early stages of fibrosis. It is speculated that miRNAs may, in the future, become biomarkers for early noninvasive diagnosis in the treatment of intestinal fibrosis. The purpose of this review is to summarise existing diagnostic methods for Crohn's disease and present recent scientific reports on molecular testing.
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Affiliation(s)
| | - Jolanta Gruszecka
- Institute of Health Sciences, Medical College of Rzeszow University, 35-959 Rzeszow, Poland
- Department of Clinical Microbiology, Clinical Hospital No. 2, 35-301 Rzeszow, Poland
| | - Rafał Filip
- Institute of Medicine, Medical College of Rzeszow University, 35-959 Rzeszow, Poland
- Department of Gastroenterology with IBD Unit, Clinical Hospital No. 2, 35-301 Rzeszow, Poland
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16
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Fiorindi C, Giudici F, Testa GD, Foti L, Romanazzo S, Tognozzi C, Mansueto G, Scaringi S, Cuffaro F, Nannoni A, Soop M, Baldini G. Multimodal Prehabilitation for Patients with Crohn's Disease Scheduled for Major Surgery: A Narrative Review. Nutrients 2024; 16:1783. [PMID: 38892714 PMCID: PMC11174506 DOI: 10.3390/nu16111783] [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: 04/29/2024] [Revised: 05/25/2024] [Accepted: 06/05/2024] [Indexed: 06/21/2024] Open
Abstract
Approximately 15-50% of patients with Crohn's disease (CD) will require surgery within ten years following the diagnosis. The management of modifiable risk factors before surgery is essential to reduce postoperative complications and to promote a better postoperative recovery. Preoperative malnutrition reduced functional capacity, sarcopenia, immunosuppressive medications, anemia, and psychological distress are frequently present in CD patients. Multimodal prehabilitation consists of nutritional, functional, medical, and psychological interventions implemented before surgery, aiming at optimizing preoperative status and improve postoperative recovery. Currently, studies evaluating the effect of multimodal prehabilitation on postoperative outcomes specifically in CD are lacking. Some studies have investigated the effect of a single prehabilitation intervention, of which nutritional optimization is the most investigated. The aim of this narrative review is to present the physiologic rationale supporting multimodal surgical prehabilitation in CD patients waiting for surgery, and to describe its main components to facilitate their adoption in the preoperative standard of care.
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Affiliation(s)
- Camilla Fiorindi
- Department of Health Science, University of Firenze, Azienda Ospedaliero Universitaria Careggi, Largo Brambilla 3, 50139 Florence, Italy; (S.R.); (C.T.); (G.M.); (F.C.); (A.N.); (G.B.)
- Multimodal Prehabilitation Center, Azienda Ospedaliera Universitaria Careggi, Largo Brambilla 6, 50135 Florence, Italy; (G.D.T.); (L.F.)
| | - Francesco Giudici
- Department of Experimental and Clinical Medicine, University of Florence, Largo Brambilla 6, 50135 Florence, Italy; (F.G.); (S.S.)
| | - Giuseppe Dario Testa
- Multimodal Prehabilitation Center, Azienda Ospedaliera Universitaria Careggi, Largo Brambilla 6, 50135 Florence, Italy; (G.D.T.); (L.F.)
- Division of Geriatric and Intensive Care Medicine, University of Florence, Azienda Ospedaliero Universitaria Careggi, Largo Brambilla 3, 50139 Florence, Italy
| | - Lorenzo Foti
- Multimodal Prehabilitation Center, Azienda Ospedaliera Universitaria Careggi, Largo Brambilla 6, 50135 Florence, Italy; (G.D.T.); (L.F.)
- Section of Anesthesiology and Intensive Care, University of Florence, Largo Brambilla 3, 50139 Florence, Italy
| | - Sara Romanazzo
- Department of Health Science, University of Firenze, Azienda Ospedaliero Universitaria Careggi, Largo Brambilla 3, 50139 Florence, Italy; (S.R.); (C.T.); (G.M.); (F.C.); (A.N.); (G.B.)
- Multimodal Prehabilitation Center, Azienda Ospedaliera Universitaria Careggi, Largo Brambilla 6, 50135 Florence, Italy; (G.D.T.); (L.F.)
| | - Cristina Tognozzi
- Department of Health Science, University of Firenze, Azienda Ospedaliero Universitaria Careggi, Largo Brambilla 3, 50139 Florence, Italy; (S.R.); (C.T.); (G.M.); (F.C.); (A.N.); (G.B.)
- Multimodal Prehabilitation Center, Azienda Ospedaliera Universitaria Careggi, Largo Brambilla 6, 50135 Florence, Italy; (G.D.T.); (L.F.)
| | - Giovanni Mansueto
- Department of Health Science, University of Firenze, Azienda Ospedaliero Universitaria Careggi, Largo Brambilla 3, 50139 Florence, Italy; (S.R.); (C.T.); (G.M.); (F.C.); (A.N.); (G.B.)
- Multimodal Prehabilitation Center, Azienda Ospedaliera Universitaria Careggi, Largo Brambilla 6, 50135 Florence, Italy; (G.D.T.); (L.F.)
| | - Stefano Scaringi
- Department of Experimental and Clinical Medicine, University of Florence, Largo Brambilla 6, 50135 Florence, Italy; (F.G.); (S.S.)
| | - Francesca Cuffaro
- Department of Health Science, University of Firenze, Azienda Ospedaliero Universitaria Careggi, Largo Brambilla 3, 50139 Florence, Italy; (S.R.); (C.T.); (G.M.); (F.C.); (A.N.); (G.B.)
| | - Anita Nannoni
- Department of Health Science, University of Firenze, Azienda Ospedaliero Universitaria Careggi, Largo Brambilla 3, 50139 Florence, Italy; (S.R.); (C.T.); (G.M.); (F.C.); (A.N.); (G.B.)
| | - Mattias Soop
- Department for IBD and Intestinal Failure Surgery, Karolinska University Hospital, SE 177 76 Stockholm, Sweden;
| | - Gabriele Baldini
- Department of Health Science, University of Firenze, Azienda Ospedaliero Universitaria Careggi, Largo Brambilla 3, 50139 Florence, Italy; (S.R.); (C.T.); (G.M.); (F.C.); (A.N.); (G.B.)
- Multimodal Prehabilitation Center, Azienda Ospedaliera Universitaria Careggi, Largo Brambilla 6, 50135 Florence, Italy; (G.D.T.); (L.F.)
- Section of Anesthesiology and Intensive Care, University of Florence, Largo Brambilla 3, 50139 Florence, Italy
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Jun YK, Ji E, Yang HR, Choi Y, Shin CM, Park YS, Kim N, Lee DH, Yoon H. Differences in the risk of clinical failure between thiopurine and methotrexate in bio-naïve patients with Crohn's disease: a Korean nationwide population-based study. Therap Adv Gastroenterol 2024; 17:17562848241248321. [PMID: 38741927 PMCID: PMC11089848 DOI: 10.1177/17562848241248321] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/11/2023] [Accepted: 03/31/2024] [Indexed: 05/16/2024] Open
Abstract
Background Although immunomodulators are widely prescribed in patients with Crohn's disease (CD), it is unclear whether there is a difference in treatment outcomes between thiopurines and methotrexate (MTX). Objective To compare the risk of clinical failure between thiopurines and MTX in bio-naïve patients with CD. Design Nationwide, population-based study. Methods We used claims data from the Korean National Health Insurance Service. After inverse probability of treatment weighting, logistic regression and Cox proportional hazard analyses were used to evaluate the risk of clinical failure in bio-naïve patients with CD treated with thiopurine (thiopurine group) or MTX (MTX group). Results Overall, 10,296 adult and pediatric patients with CD [9912 (96.3%) and 384 (3.7%) in the thiopurine and MTX groups, respectively] were included. The odds ratios (ORs) of failure to induce remission were significantly higher in the MTX group than in the thiopurine group [adjusted OR (aOR), 1.115; 95% confidence interval (CI), 1.045-1.190; p = 0.001]. However, the opposite result was observed only in patients without concomitant steroid use: the MTX group had a lower risk of induction failure than the thiopurine group (aOR, 0.740; 95% CI, 0.673-0.813; p < 0.001). The risk of overall maintenance failure was higher in the MTX group than in the thiopurine group [adjusted hazard ratio (aHR), 1.117; 95% CI, 1.047-1.191; p = 0.001]. The risk of overall maintenance failure was higher in the standard-dose MTX group than in the low-dose MTX group (aHR, 1.296; 95% CI, 1.134-1.480; p < 0.001). There was no significant difference in the risk of maintenance failure according to the administration route of MTX. Conclusion Thiopurine is more effective than MTX in inducing and maintaining remission in bio-naïve patients with CD; however, the concomitant use of steroids influences inducing remission.
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Affiliation(s)
- Yu Kyung Jun
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, South Korea
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, South Korea
| | - Eunjeong Ji
- Medical Research Collaborating Center, Seoul National University Bundang Hospital, Seongnam, South Korea
| | - Hye Ran Yang
- Department of Pediatrics, Seoul National University Bundang Hospital, Seongnam, South Korea
| | - Yonghoon Choi
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, South Korea
| | - Cheol Min Shin
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, South Korea
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, South Korea
| | - Young Soo Park
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, South Korea
| | - Nayoung Kim
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, South Korea
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, South Korea
| | - Dong Ho Lee
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, South Korea
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, South Korea
| | - Hyuk Yoon
- Department of Internal Medicine, Seoul National University Bundang Hospital, 173-82, Gumi-ro, Bundang-gu, Seongnam, Gyeonggi-do 463-707, South Korea
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, South Korea
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18
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Dipasquale V, Milone E, Nigro S, Alibrandi A, Antonelli E, Di Fabrizio D, Romeo C, Navarra G, Romano C. Risk Factors for Complications and Disease Recurrence after Ileocecal Resection for Crohn's Disease in Children and Adults. Biomedicines 2024; 12:862. [PMID: 38672216 PMCID: PMC11047859 DOI: 10.3390/biomedicines12040862] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2024] [Revised: 04/08/2024] [Accepted: 04/11/2024] [Indexed: 04/28/2024] Open
Abstract
This study reports the complication and disease recurrence rates for ileocecal resection for pediatric and adult Crohn's disease (CD) and identifies perioperative risk factors for these adverse outcomes in the two groups. Patients who underwent ileocecal resection for CD in a tertiary hospital in Italy (2010-2021) were included. Risk factors for postoperative complications and clinical and surgical disease recurrences were investigated with multivariate models. A total of 96 patients were included (children, 25%). There were no intraoperative complications. Thirty-one (32.3%) patients experienced 35 (36.5%) postoperative complications, and five (5.2%) were severe (Clavien-Dindo III-IV-V), with no intergroup difference for either overall postoperative complication rate (p = 0.257) or severe postoperative complication rate (p = 0.097). Most of these (77.1%) occurred within 30 days after surgery, especially in adults (p = 0.013). The multivariate analysis did not show risk factors for postoperative complications. Clinical and surgical recurrence rates after 5 years were 46.8% and 14.6%, respectively, with no intergroup rate differences. Clinical disease recurrence was positively correlated with previous abdominal surgery (p = 0.047) and negatively correlated with preoperative Hb levels (p = 0.046). A positive correlation was found between perianal disease and both clinical (p = 0.045) and surgical disease recurrences (p = 0.045). Urgent surgery was positively associated with surgical disease recurrence (p = 0.045). Notably, no children underwent urgent surgery in this study. In conclusion, the risk of postoperative complications among CD patients receiving ileocecal resection remains high, but most of them are nonserious. Some factors, such as urgent surgery, may increase the risk of disease recurrences.
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Affiliation(s)
- Valeria Dipasquale
- Pediatric Gastroenterology and Cystic Fibrosis Unit, Department of Human Pathology in Adulthood and Childhood “G. Barresi”, University Hospital “G. Martino”, 98122 Messina, Italy
| | - Erica Milone
- Surgical Oncology Division, Department of Human Pathology in Adulthood and Childhood “G. Barresi”, University Hospital “G. Martino”, 98122 Messina, Italy (S.N.)
| | - Stefania Nigro
- Surgical Oncology Division, Department of Human Pathology in Adulthood and Childhood “G. Barresi”, University Hospital “G. Martino”, 98122 Messina, Italy (S.N.)
| | - Angela Alibrandi
- Statistical and Mathematical Sciences Unit, Department of Economics, University of Messina, 98122 Messina, Italy
| | - Enrica Antonelli
- Pediatric Surgery Unit, Department of Human Pathology in Adulthood and Childhood “G. Barresi”, University Hospital “G. Martino”, 98122 Messina, Italy; (E.A.); (D.D.F.); (C.R.)
| | - Donatella Di Fabrizio
- Pediatric Surgery Unit, Department of Human Pathology in Adulthood and Childhood “G. Barresi”, University Hospital “G. Martino”, 98122 Messina, Italy; (E.A.); (D.D.F.); (C.R.)
| | - Carmelo Romeo
- Pediatric Surgery Unit, Department of Human Pathology in Adulthood and Childhood “G. Barresi”, University Hospital “G. Martino”, 98122 Messina, Italy; (E.A.); (D.D.F.); (C.R.)
| | - Giuseppe Navarra
- Surgical Oncology Division, Department of Human Pathology in Adulthood and Childhood “G. Barresi”, University Hospital “G. Martino”, 98122 Messina, Italy (S.N.)
| | - Claudio Romano
- Pediatric Gastroenterology and Cystic Fibrosis Unit, Department of Human Pathology in Adulthood and Childhood “G. Barresi”, University Hospital “G. Martino”, 98122 Messina, Italy
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19
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Rošić Despalatović B, Babić M, Bratanić A, Tonkić A, Ardalić Ž, Vilović K. The Impact of Phenotype of Inflammatory Bowel Diseases, Inflammation Activity and Therapy on Mucosal Mature Cd83 + Dendritic Cell. J Clin Med 2024; 13:2070. [PMID: 38610835 PMCID: PMC11012704 DOI: 10.3390/jcm13072070] [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: 01/31/2024] [Revised: 03/08/2024] [Accepted: 04/02/2024] [Indexed: 04/14/2024] Open
Abstract
Background: Crohn's disease (CD) and ulcerative colitis (UC) are well-defined phenotypes of chronic inflammatory bowel diseases (IBDs). A mechanism of inflammation in these diseases is partially controlled by the intestinal dendritic cell (DC). In this study, we observed a mature CD83+ DC in colonic bioptic samples, and its correlation with disease phenotype and activity. Methods: The study included 219 subjects: 100 with UC, 44 with CD and 75 healthy subjects. Colonic biopsy specimens were incubated with the primary antibody Anti-CD83. Intraepithelial CD83+ DCs were counted per 100 enterocytes. The presence of CD83+ DC was analysed according to the type of IBD, histopathologic inflammation activity and treatment outcome. Results: The presence of mature CD83+ DCs (0, ≥1) differed according to disease types of IBD (p = 0.001), histologic inflammation activity (p = 0.049) and applied therapy (p = 0.001). The odds for CD83+ DC presence were 5.2 times higher in the CD group than in the control/UC group. The odds for CD83+ DC presence were 2.6 times higher in subjects without inflammation or chronic inflammation than with acute inflammation. They were also 3.7 times higher in subjects without therapy. The cut-off value 0.5 CD83+ DC (Rock analysis area = 0.699; SE 0.046; p < 0.001; 95% CI: 0.609-0.788) had been assessed as a differentiation marker between UC and CD. Conclusion: Presence of CD83+ DC could be used as a possible parameter in distinction between UC and CD, as well as a predictor of inflammation activity and treatment outcome.
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Affiliation(s)
| | - Marija Babić
- Medical School, University of Split, 21000 Split, Croatia;
| | - Andre Bratanić
- Department of Gastroenterology and Hepatology, University Hospital Split, 21000 Split, Croatia; (A.T.); (Ž.A.)
| | - Ante Tonkić
- Department of Gastroenterology and Hepatology, University Hospital Split, 21000 Split, Croatia; (A.T.); (Ž.A.)
| | - Žarko Ardalić
- Department of Gastroenterology and Hepatology, University Hospital Split, 21000 Split, Croatia; (A.T.); (Ž.A.)
| | - Katarina Vilović
- Department of Pathology, University Hospital Split, 21000 Split, Croatia;
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20
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Yamamoto-Furusho J, López-Gómez J, Bosques-Padilla F, Martínez-Vázquez M, De-León-Rendón J. Primer consenso mexicano de la enfermedad de Crohn. REVISTA DE GASTROENTEROLOGÍA DE MÉXICO 2024; 89:280-311. [DOI: 10.1016/j.rgmx.2024.03.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/26/2024]
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21
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Yamamoto-Furusho JK, López-Gómez JG, Bosques-Padilla FJ, Martínez-Vázquez MA, De-León-Rendón JL. First Mexican Consensus on Crohn's disease. REVISTA DE GASTROENTEROLOGIA DE MEXICO (ENGLISH) 2024; 89:280-311. [PMID: 38762431 DOI: 10.1016/j.rgmxen.2024.03.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/11/2023] [Accepted: 03/19/2024] [Indexed: 05/20/2024]
Abstract
INTRODUCTION Crohn's disease (CD) is a subtype of chronic and incurable inflammatory bowel disease. It can affect the entire gastrointestinal tract and its etiology is unknown. OBJECTIVE The aim of this consensus was to establish the most relevant aspects related to definitions, diagnosis, follow-up, medical treatment, and surgical treatment of Crohn's disease in Mexico. MATERIAL AND METHODS Mexican specialists in the areas of gastroenterology and inflammatory bowel disease were summoned. The consensus was divided into five modules, with 69 statements. Applying the Delphi panel method, the pre-meeting questions were sent to the participants, to be edited and weighted. At the face-to-face meeting, all the selected articles were shown, underlining their level of clinical evidence; all the statements were discussed, and a final vote was carried out, determining the percentage of agreement for each statement. RESULTS The first Mexican consensus on Crohn's disease was produced, in which recommendations for definitions, classifications, diagnostic aspects, follow-up, medical treatment, and surgical treatment were established. CONCLUSIONS Updated recommendations are provided that focus on definitions, classifications, diagnostic criteria, follow-up, and guidelines for conventional medical treatment, biologic therapy, and small molecule treatment, as well as surgical management.
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Affiliation(s)
- J K Yamamoto-Furusho
- Clínica de Enfermedad Inflamatoria Intestinal, Departamento de Gastroenterología, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico.
| | - J G López-Gómez
- Clínica de Enfermedad Inflamatoria Intestinal, Servicio de Gastroenterología, Centro Médico Nacional 20 de Noviembre, Instituto de Seguridad y Servicios Sociales de los Trabajadores del Estado (ISSSTE), Mexico City, Mexico
| | - F J Bosques-Padilla
- Departamento de Gastroenterología, Hospital Universitario de la Universidad Autónoma de Nuevo León, Monterrey, Mexico
| | | | - J L De-León-Rendón
- Clínica de Enfermedad Inflamatoria Intestinal, Servicio de Coloproctología, Hospital General de México, Mexico City, Mexico
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22
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Correia I, Oliveira PA, Antunes ML, Raimundo MDG, Moreira AC. Is There Evidence of Crohn's Disease Exclusion Diet (CDED) in Remission of Active Disease in Children and Adults? A Systematic Review. Nutrients 2024; 16:987. [PMID: 38613020 PMCID: PMC11013840 DOI: 10.3390/nu16070987] [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: 02/26/2024] [Revised: 03/18/2024] [Accepted: 03/22/2024] [Indexed: 04/14/2024] Open
Abstract
Crohn's disease (CD) is an inflammatory bowel disease. Previous research has explored the impact of diet on CD, as specific dietary components can influence gut microbiota and immune responses, contributing to damage in the gastrointestinal tract. The Crohn's Disease Exclusion Diet (CDED) is based on an exclusion diet; it is a recent dietary approach that is often used alongside partial enteral nutrition (PEN) and aims to induce disease remission by excluding certain dietary components. This study assesses the current evidence for the effectiveness of the CDED + PEN in achieving remission in both children and adults with active CD. Our systematic review followed PRISMA recommendations and was registered in PROSPERO with CRD number 42022335076. The searched databases were PubMed/MEDLINE, Cochrane Library, Scopus, and Web of Science. The included studies were analyzed using Rayyan software, and the risk of bias was assessed with Cochrane RevMan 5.0 software. The primary assessed outcome was clinical remission, evaluated with validated questionnaire scores such as PCDAI, CDAI, or HBI. All analyzed papers yielded promising results. Notably, the CDED + PEN demonstrated better tolerance than exclusive enteral nutrition (EEN), resulting in higher adherence rates. Therefore, the CDED + PEN appears to be a viable alternative for induction remission in active disease for both children and adults with CD.
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Affiliation(s)
- Inês Correia
- ESTeSL—Escola Superior de Tecnologia da Saúde de Lisboa, Instituto Politécnico de Lisboa, 1990-096 Lisboa, Portugal; (P.A.O.); (M.L.A.); (M.d.G.R.); (A.C.M.)
- Faculdade de Medicina, Universidade de Lisboa, 1649-028 Lisboa, Portugal
- Hospital do Espírito Santo de Évora, EPE, 7000-811 Évora, Portugal
- H&TRC—Health & Technology Research Center, ESTeSL—Escola Superior de Tecnologia da Saúde, Instituto Politécnico de Lisboa, 1990-096 Lisboa, Portugal
| | - Patrícia Almeida Oliveira
- ESTeSL—Escola Superior de Tecnologia da Saúde de Lisboa, Instituto Politécnico de Lisboa, 1990-096 Lisboa, Portugal; (P.A.O.); (M.L.A.); (M.d.G.R.); (A.C.M.)
| | - Maria Luz Antunes
- ESTeSL—Escola Superior de Tecnologia da Saúde de Lisboa, Instituto Politécnico de Lisboa, 1990-096 Lisboa, Portugal; (P.A.O.); (M.L.A.); (M.d.G.R.); (A.C.M.)
- APPsyCI—Applied Psychology Research Center Capabilities & Inclusion, ISPA—Instituto Universitário, 1149-041 Lisboa, Portugal
| | - Maria da Graça Raimundo
- ESTeSL—Escola Superior de Tecnologia da Saúde de Lisboa, Instituto Politécnico de Lisboa, 1990-096 Lisboa, Portugal; (P.A.O.); (M.L.A.); (M.d.G.R.); (A.C.M.)
- Hospital do Espírito Santo de Évora, EPE, 7000-811 Évora, Portugal
| | - Ana Catarina Moreira
- ESTeSL—Escola Superior de Tecnologia da Saúde de Lisboa, Instituto Politécnico de Lisboa, 1990-096 Lisboa, Portugal; (P.A.O.); (M.L.A.); (M.d.G.R.); (A.C.M.)
- H&TRC—Health & Technology Research Center, ESTeSL—Escola Superior de Tecnologia da Saúde, Instituto Politécnico de Lisboa, 1990-096 Lisboa, Portugal
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23
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Yuan Z, Ye J, Liu B, Zhang L. Unraveling the role of autophagy regulation in Crohn's disease: from genetic mechanisms to potential therapeutics. ADVANCED BIOTECHNOLOGY 2024; 2:14. [PMID: 39883213 PMCID: PMC11740883 DOI: 10.1007/s44307-024-00021-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/27/2024] [Revised: 02/29/2024] [Accepted: 03/10/2024] [Indexed: 01/31/2025]
Abstract
Autophagy serves as the primary intracellular degradation mechanism in which damaged organelles and self-cytoplasmic proteins are transported to the lysosome for degradation. Crohn's disease, an idiopathic chronic inflammatory disorder of the gastrointestinal tract, manifests in diverse regions of the digestive system. Recent research suggests that autophagy modulation may be a new avenue for treating Crohn's disease, and several promising small-molecule modulators of autophagy have been reported as therapeutic options. In this review, we discuss in detail how mutations in autophagy-related genes function in Crohn's disease and summarize the modulatory effects on autophagy of small-molecule drugs currently used for Crohn's disease treatment. Furthermore, we delve into the therapeutic potential of small-molecule autophagy inducers on Crohn's disease, emphasizing the prospects for development in this field. We aim to highlight the significance of autophagy modulation in Crohn's disease, with the aspiration of contributing to the development of more efficacious treatments that can alleviate their suffering, and improve their quality of life.
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Affiliation(s)
- Ziyue Yuan
- Sichuan Engineering Research Center for Biomimetic Synthesis of Natural Drugs, School of Life Science and Engineering, Southwest Jiaotong University, Chengdu, 610031, China
| | - Jing Ye
- Department of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, China
| | - Bo Liu
- Department of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, China.
| | - Lan Zhang
- Sichuan Engineering Research Center for Biomimetic Synthesis of Natural Drugs, School of Life Science and Engineering, Southwest Jiaotong University, Chengdu, 610031, China.
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24
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Dignass A, Esters P, Flauaus C. Upadacitinib in Crohn's disease. Expert Opin Pharmacother 2024; 25:359-370. [PMID: 38512115 DOI: 10.1080/14656566.2024.2333964] [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: 01/17/2024] [Accepted: 03/19/2024] [Indexed: 03/22/2024]
Abstract
INTRODUCTION The small molecule and oral selective and reversible Janus kinase (JAK) inhibitor upadacitinib has been approved for the treatment of moderate to severe active Crohn's disease (CD) in adult patients since April 2023 by EMA/FDA. AREAS COVERED The approval is based on the two induction studies a maintenance study showing that upadacitinib induction and maintenance therapy was superior to placebo. The approval of upadacitinib in CD expands the therapeutic armamentarium for the management of inflammatory bowel diseases (IBD). Upadacitinib is the first and only JAK inhibitor approved in patients with CD and provides a novel mechanism of action and the first advanced oral treatment option for patients with CD. Upadacitinib is approved for the treatment of other immunologically mediated disorders, including ulcerative colitis, rheumatoid arthritis, psoriasis arthritis, axial spondylarthritis, ankylosing spondylitis, and atopic dermatitis. Treatment of atopic dermatitis has been approved from the age of 12 years. EXPERT OPINION Upadacitinib may cause relevant changes of our current treatment algorithms for Crohn's disease. Further real-world studies and head-to-head comparisons are needed to position upadacitinib in our current treatment algorithms for CD.
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Affiliation(s)
- Axel Dignass
- Department of Medicine I, Agaplesion Markus Hospital, Frankfurt/Main, Germany
| | - Philip Esters
- Department of Medicine I, Agaplesion Markus Hospital, Frankfurt/Main, Germany
| | - Cathrin Flauaus
- AbbVie Deutschland GmbH & Co. KG, Medical Immunology, Wiesbaden, Germany
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25
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James JP, Riis LB, Søkilde R, Malham M, Høgdall E, Langholz E, Nielsen BS. Short noncoding RNAs as predictive biomarkers for the development from inflammatory bowel disease unclassified to Crohn's disease or ulcerative colitis. PLoS One 2024; 19:e0297353. [PMID: 38408066 PMCID: PMC10896517 DOI: 10.1371/journal.pone.0297353] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2023] [Accepted: 12/22/2023] [Indexed: 02/28/2024] Open
Abstract
Numerous pathogenic processes are mediated by short noncoding RNAs (sncRNA). Twenty percent of inflammatory bowel disease (IBD) patients are labelled as IBD unclassified (IBDU) at disease onset. Most IBDU patients are reclassified as Crohn's disease (CD) or ulcerative colitis (UC) within few years. Since the therapeutic methods for CD and UC differ, biomarkers that can forecast the categorization of IBDU into CD or UC are highly desired. Here, we investigated whether sncRNAs can predict CD or UC among IBDU patients. 35 IBDU patients who were initially diagnosed with IBDU were included in this retrospective investigation; of them, 12, 15, and 8 were reclassified into CD (IBDU-CD), UC (IBDU-UC), or remained as IBDU (IBDU-IBDU), respectively. Eight IBD patients, were included as references. SncRNA profiling on RNA from mucosal biopsies were performed using Affymetrix miRNA 4.0 array. Selected probe sets were validated using RT-qPCR. Among all patients and only adults, 306 and 499 probe sets respectively were differentially expressed between IBDU-CD and IBDU-UC. Six of the probe sets were evaluated by RT-qPCR, of which miR-182-5p, miR-451a and ENSG00000239080 (snoU13) together with age and sex resulted in an AUC of 78.6% (95% CI: 60-97) in discriminating IBDU-CD from IBDU-UC. Based on the three sncRNAs profile it is possible to predict if IBDU patients within 3 years will be reclassified as CD or UC. We showed that the expression profile of IBDU patients differ from that of definite CD or UC, suggesting that a subgroup of IBDU patients may compose a third unique IBD subtype.
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Affiliation(s)
- Jaslin P. James
- Department of Pathology, Herlev University Hospital, Herlev, Denmark
| | - Lene Buhl Riis
- Department of Pathology, Herlev University Hospital, Herlev, Denmark
- Institute of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark
| | - Rolf Søkilde
- Bioneer A/S, Hørsholm, Kogle Allé 2, Hørsholm, Denmark
| | - Mikkel Malham
- The Pediatric Department, Copenhagen University Hospital—Amager and Hvidovre, Hvidovre, Denmark
- Copenhagen Center for Inflammatory Bowel Disease in Children, Adolescents and Adults, Hvidovre Hospital, University of Copenhagen, Hvidovre, Denmark
| | - Estrid Høgdall
- Department of Pathology, Herlev University Hospital, Herlev, Denmark
- Institute of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark
| | - Ebbe Langholz
- Institute of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark
- Gastroenheden, Herlev University Hospital, Herlev, Denmark
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26
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Kwon S, Judson MA. Clinical Pharmacology in Sarcoidosis: How to Use and Monitor Sarcoidosis Medications. J Clin Med 2024; 13:1250. [PMID: 38592130 PMCID: PMC10932410 DOI: 10.3390/jcm13051250] [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: 01/15/2024] [Revised: 02/11/2024] [Accepted: 02/13/2024] [Indexed: 04/10/2024] Open
Abstract
When sarcoidosis needs treatment, pharmacotherapy is usually required. Although glucocorticoids work reliably and relatively quickly for sarcoidosis, these drugs are associated with numerous significant side effects. Such side effects are common in sarcoidosis patients, as the disease frequently has a chronic course and glucocorticoid treatment courses are often prolonged. For these reasons, corticosteroid-sparing and corticosteroid-replacing therapies are often required for sarcoidosis. Unfortunately, many healthcare providers who care for sarcoidosis patients are not familiar with the use of these agents. In this manuscript, we provide a review of the pharmacotherapy of sarcoidosis. We discuss the mechanism of action, dosing, side-effect profile, approach to monitoring and patient counselling concerning glucocorticoids, and the common alternative drugs recommended for use in the recent European Respiratory Society (Lausanne, Switzerland) Sarcoidosis Treatment Guidelines. We also discuss the use of these agents in special situations including hepatic insufficiency, renal insufficiency, pregnancy, breastfeeding, vaccination, and drug-drug interactions. It is hoped that this manuscript will provide valuable practical guidance to clinicians who care for sarcoidosis patients.
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Affiliation(s)
- Sooyeon Kwon
- Samuel S. Stratton Veterans Affairs Medical Center, Albany, NY 12208, USA
| | - Marc A. Judson
- Division of Pulmonary and Critical Care Medicine, Albany Medical College, Albany, NY 12208, USA;
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27
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Vălean D, Zaharie R, Țaulean R, Usatiuc L, Zaharie F. Recent Trends in Non-Invasive Methods of Diagnosis and Evaluation of Inflammatory Bowel Disease: A Short Review. Int J Mol Sci 2024; 25:2077. [PMID: 38396754 PMCID: PMC10889152 DOI: 10.3390/ijms25042077] [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: 01/16/2024] [Revised: 02/04/2024] [Accepted: 02/06/2024] [Indexed: 02/25/2024] Open
Abstract
Inflammatory bowel diseases are a conglomerate of disorders causing inflammation of the gastrointestinal tract, which have gained a significant increase in prevalence in the 21st century. As they present a challenge in the terms of diagnosis as well as treatment, IBDs can present an overwhelming impact on the individual and can take a toll on healthcare costs. Thus, a quick and precise diagnosis is required in order to prevent the high number of complications that can arise from a late diagnosis as well as a misdiagnosis. Although endoscopy remains the primary method of evaluation for IBD, recent trends have highlighted various non-invasive methods of diagnosis as well as reevaluating previous ones. This review focused on the current non-invasive methods in the diagnosis of IBD, exploring their possible implementation in the near future, with the goal of achieving earlier, feasible, and cheap methods of diagnosis as well as prognosis in IBD.
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Affiliation(s)
- Dan Vălean
- Regional Institute of Gastroenterology and Hepatology “Octavian Fodor”, 400162 Cluj-Napoca, Romania; (D.V.); (R.Ț.); (F.Z.)
- Department of General Surgery, University of Medicine and Pharmacy “Iuliu Hațieganu”, 400347 Cluj-Napoca, Romania
| | - Roxana Zaharie
- Regional Institute of Gastroenterology and Hepatology “Octavian Fodor”, 400162 Cluj-Napoca, Romania; (D.V.); (R.Ț.); (F.Z.)
- Department of Gastroenterology, University of Medicine and Pharmacy “Iuliu Hațieganu”, 400347 Cluj-Napoca, Romania
| | - Roman Țaulean
- Regional Institute of Gastroenterology and Hepatology “Octavian Fodor”, 400162 Cluj-Napoca, Romania; (D.V.); (R.Ț.); (F.Z.)
- Department of General Surgery, University of Medicine and Pharmacy “Iuliu Hațieganu”, 400347 Cluj-Napoca, Romania
| | - Lia Usatiuc
- Department of Patophysiology, University of Medicine and Pharmacy “Iuliu Hațieganu”, 400347 Cluj-Napoca, Romania;
| | - Florin Zaharie
- Regional Institute of Gastroenterology and Hepatology “Octavian Fodor”, 400162 Cluj-Napoca, Romania; (D.V.); (R.Ț.); (F.Z.)
- Department of General Surgery, University of Medicine and Pharmacy “Iuliu Hațieganu”, 400347 Cluj-Napoca, Romania
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28
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Klemenak M, Zupan M, Riznik P, Krencnik T, Dolinsek J. Evolving Landscape of Paediatric Inflammatory Bowel Disease: Insights from a Decade-Long Study in North-East Slovenia on Incidence, Management, Diagnostic Delays, and Early Biologic Intervention. Diagnostics (Basel) 2024; 14:188. [PMID: 38248065 PMCID: PMC10813920 DOI: 10.3390/diagnostics14020188] [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: 12/15/2023] [Revised: 01/10/2024] [Accepted: 01/11/2024] [Indexed: 01/23/2024] Open
Abstract
BACKGROUND In the past decade, significant progress has been achieved in the care of children with inflammatory bowel disease (IBD). Our study concentrated on assessing the incidence and management of IBD in children in North-Eastern Slovenia over a 10-year period. METHODS Medical data from children and adolescents diagnosed with IBD in North-Eastern Slovenia (2014-2023) was analysed. Disease incidence and management of children were assessed. Findings were compared between two periods (2014-2019 and 2020-2023, coinciding with the COVID-19 pandemic). RESULTS 87 patients (median age 15.5 year; 50.6% male) with IBD (43.7% Crohn's disease (CD)), diagnosed between 2014 and 2023 were included. Extraintestinal manifestations were more common in CD than ulcerative colitis (UC) (15.8% vs. 2.4%, p < 0.05). Median delay from symptom onset to diagnosis was 2 months, lower in UC than CD (NS). Mean annual IBD incidence per 100,000 children aged 0 to 19 years was 6.4 (95% CI 4.4-8.3), slightly lower for CD than UC (2.8/100,000 vs. 3.1/100,000). In the second period, IBD incidence significantly rose (9.1 vs. 4.6, p < 0.05). During this period, 53% of CD patients transitioned to biological treatment within three months of diagnosis. CONCLUSION IBD incidence rose among children in North-Eastern Slovenia over the past decade. Additionally, more children with CD underwent biological therapy in the second period.
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Affiliation(s)
- Martina Klemenak
- Department of Gastroenterology, Hepatology and Nutrition, Pediatric Clinic, University Medical Centre Maribor, 2000 Maribor, Slovenia (J.D.)
| | - Manca Zupan
- Faculty of Medicine, University of Maribor, 2000 Maribor, Slovenia
| | - Petra Riznik
- Department of Gastroenterology, Hepatology and Nutrition, Pediatric Clinic, University Medical Centre Maribor, 2000 Maribor, Slovenia (J.D.)
| | - Tomaz Krencnik
- Department of Gastroenterology, Hepatology and Nutrition, Pediatric Clinic, University Medical Centre Maribor, 2000 Maribor, Slovenia (J.D.)
| | - Jernej Dolinsek
- Department of Gastroenterology, Hepatology and Nutrition, Pediatric Clinic, University Medical Centre Maribor, 2000 Maribor, Slovenia (J.D.)
- Faculty of Medicine, University of Maribor, 2000 Maribor, Slovenia
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29
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Liu RX, Li H, Towbin AJ, Ata NA, Smith EA, Tkach JA, Denson LA, He L, Dillman JR. Machine Learning Diagnosis of Small-Bowel Crohn Disease Using T2-Weighted MRI Radiomic and Clinical Data. AJR Am J Roentgenol 2024; 222:e2329812. [PMID: 37530398 DOI: 10.2214/ajr.23.29812] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/03/2023]
Abstract
BACKGROUND. Radiologists have variable diagnostic performance and considerable interreader variability when interpreting MR enterography (MRE) examinations for suspected Crohn disease (CD). OBJECTIVE. The purposes of this study were to develop a machine learning method for predicting ileal CD by use of radiomic features of ileal wall and mesenteric fat from noncontrast T2-weighted MRI and to compare the performance of the method with that of expert radiologists. METHODS. This single-institution study included retrospectively identified patients who underwent MRE for suspected ileal CD from January 1, 2020, to January 31, 2021, and prospectively enrolled participants (patients with newly diagnosed ileal CD or healthy control participants) from December 2018 to October 2021. Using axial T2-weighted SSFSE images, a radiologist selected two slices showing greatest terminal ileal wall thickening. Four ROIs were segmented, and radiomic features were extracted from each ROI. After feature selection, support-vector machine models were trained to classify the presence of ileal CD. Three fellowship-trained pediatric abdominal radiologists independently classified the presence of ileal CD on SSFSE images. The reference standard was clinical diagnosis of ileal CD based on endoscopy and biopsy results. Radiomic-only, clinical-only, and radiomic-clinical ensemble models were trained and evaluated by nested cross-validation. RESULTS. The study included 135 participants (67 female, 68 male; mean age, 15.2 ± 3.2 years); 70 were diagnosed with ileal CD. The three radiologists had accuracies of 83.7% (113/135), 88.1% (119/135), and 86.7% (117/135) for diagnosing CD; consensus accuracy was 88.1%. Interradiologist agreement was substantial (κ = 0.78). The best-performing ROI was bowel core (AUC, 0.95; accuracy, 89.6%); other ROIs had worse performance (whole-bowel AUC, 0.86; fat-core AUC, 0.70; whole-fat AUC, 0.73). For the clinical-only model, AUC was 0.85 and accuracy was 80.0%. The ensemble model combining bowel-core radiomic and clinical models had AUC of 0.98 and accuracy of 93.5%. The bowel-core radiomic-only model had significantly greater accuracy than radiologist 1 (p = .009) and radiologist 2 (p = .02) but not radiologist 3 (p > .99) or the radiologists in consensus (p = .05). The ensemble model had greater accuracy than the radiologists in consensus (p = .02). CONCLUSION. A radiomic machine learning model predicted CD diagnosis with better performance than two of three expert radiologists. Model performance improved when radiomic data were ensembled with clinical data. CLINICAL IMPACT. Deployment of a radiomic-based model including T2-weighted MRI data could decrease interradiologist variability and increase diagnostic accuracy for pediatric CD.
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Affiliation(s)
- Richard X Liu
- Department of Radiology, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, 3333 Burnet Ave, Cincinnati, OH 45229
| | - Hailong Li
- Department of Radiology, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, 3333 Burnet Ave, Cincinnati, OH 45229
- Imaging Research Center, Cincinnati Children's Hospital Medical Center, Cincinnati, OH
| | - Alexander J Towbin
- Department of Radiology, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, 3333 Burnet Ave, Cincinnati, OH 45229
| | - Nadeen Abu Ata
- Department of Radiology, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, 3333 Burnet Ave, Cincinnati, OH 45229
| | - Ethan A Smith
- Department of Radiology, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, 3333 Burnet Ave, Cincinnati, OH 45229
| | - Jean A Tkach
- Department of Radiology, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, 3333 Burnet Ave, Cincinnati, OH 45229
| | - Lee A Denson
- Department of Pediatrics, Division of Gastroenterology, Hepatology, and Nutrition, Cincinnati Children's Hospital Medical Center, Cincinnati, OH
| | - Lili He
- Department of Radiology, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, 3333 Burnet Ave, Cincinnati, OH 45229
- Imaging Research Center, Cincinnati Children's Hospital Medical Center, Cincinnati, OH
| | - Jonathan R Dillman
- Department of Radiology, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, 3333 Burnet Ave, Cincinnati, OH 45229
- Imaging Research Center, Cincinnati Children's Hospital Medical Center, Cincinnati, OH
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Iaquinto G, Aufiero VR, Mazzarella G, Lucariello A, Panico L, Melina R, Iaquinto S, De Luca A, Sellitto C. Pathogens in Crohn's Disease: The Role of Adherent Invasive Escherichia coli. Crit Rev Eukaryot Gene Expr 2024; 34:83-99. [PMID: 38305291 DOI: 10.1615/critreveukaryotgeneexpr.2023050088] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/03/2024]
Abstract
In Crohn's disease (CD), gut dysbiosis is marked by the prevalence of pathogenic bacterial species. Although several microbes have been reported as risk factors or causative agents of CD, it is not yet clear which is the real trigger of the disease. Thirty years ago, a new pathovar of Escherichia coli strain was isolated in the ileal mucosa of CD patients. This strain, called adherent invasive E. coli (AIEC), for its ability to invade the intestinal mucosa, could represent the causative agent of the disease. Several authors studied the mechanisms by which the AIEC penetrate and replicate within macrophages, and release inflammatory cytokines sustaining inflammation. In this review we will discuss about the role of AIEC in the pathogenesis of CD, the virulence factors mediating adhesion and invasion of AIEC in mucosal tissue, the environmental conditions improving AIEC survival and replication within macrophages. Finally, we will also give an overview of the new strategies developed to limit AIEC overgrowth.
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Affiliation(s)
- Gaetano Iaquinto
- Gastroenterology Division, S. Rita Hospital, Atripalda, Avellino, Italy
| | - Vera Rotondi Aufiero
- Institute of Food Sciences, CNR, Avellino, Italy and Department of Translational Medical Science and E.L.F.I.D, University "Federico II" Napoli, Italy
| | - Giuseppe Mazzarella
- Institute of Food Sciences, CNR, Avellino, Italy and Department of Translational Medical Science and E.L.F.I.D, University "Federico II" Napoli, Italy
| | - Angela Lucariello
- Department of Sport Sciences and Wellness, University of Naples "Parthenope," 80100, Naples, Italy
| | - Luigi Panico
- Pathological Anatomy and Histology Unit, Monaldi Hospital, Napoli, Italy
| | - Raffaele Melina
- Department of Gastroenterology, San G. Moscati Hospital, Avellino, Italy
| | | | - Antonio De Luca
- Department of Mental Health and Physics, Preventive Medicine, University of Campania "Luigi Vanvitelli," Naples, Italy
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Dhaliwal G, Patrone MV, Bickston SJ. Venous Thromboembolism in Patients with Inflammatory Bowel Disease. J Clin Med 2023; 13:251. [PMID: 38202258 PMCID: PMC10780135 DOI: 10.3390/jcm13010251] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2023] [Revised: 12/16/2023] [Accepted: 12/21/2023] [Indexed: 01/12/2024] Open
Abstract
Patients diagnosed with inflammatory bowel disease (IBD), which encompasses Crohn's disease and ulcerative colitis, experience chronic inflammation of the gastrointestinal tract. Those with IBD face a higher risk of developing venous thromboembolism (VTE) compared to individuals without IBD. This escalated risk is associated with various factors, some modifiable and others non-modifiable, with disease activity being the primary concern. Interestingly, Janus Kinase inhibitors approved for the treatment of IBD may be associated with an increased risk of VTE but only in patients that have other underlying risk factors leading to an overall increased VTE risk. Several recognized medical societies have recommended the use of VTE prophylaxis for hospitalized individuals with IBD. The association between VTE and IBD and the need for pharmacologic prophylaxis remains under-recognized. Increased awareness of this complication can hopefully protect patients from a potentially deadly complication.
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Affiliation(s)
- Galvin Dhaliwal
- Division of Gastroenterology, Hepatology and Nutrition, Virginia Commonwealth University, Richmond, VA 23219, USA; (M.V.P.); (S.J.B.)
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Clinton JW, Cross RK. Personalized Treatment for Crohn's Disease: Current Approaches and Future Directions. Clin Exp Gastroenterol 2023; 16:249-276. [PMID: 38111516 PMCID: PMC10726957 DOI: 10.2147/ceg.s360248] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/30/2023] [Accepted: 12/04/2023] [Indexed: 12/20/2023] Open
Abstract
Crohn's disease is a complex, relapsing and remitting inflammatory disorder of the gastrointestinal tract with a variable disease course. While the treatment options for Crohn's disease have dramatically increased over the past two decades, predicting individual patient response to treatment remains a challenge. As a result, patients often cycle through multiple different therapies before finding an effective treatment which can lead to disease complications, increased costs, and decreased quality of life. Recently, there has been increased emphasis on personalized medicine in Crohn's disease to identify individual patients who require early advanced therapy to prevent complications of their disease. In this review, we summarize our current approach to management of Crohn's disease by identifying risk factors for severe or disabling disease and tailoring individual treatments to patient-specific goals. Lastly, we outline our knowledge gaps in implementing personalized Crohn's disease treatment and describe the future directions in precision medicine.
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Affiliation(s)
- Joseph William Clinton
- Department of Medicine, Division of Gastroenterology and Hepatology, University of Maryland School of Medicine, Baltimore, MD, USA
| | - Raymond Keith Cross
- Department of Medicine, Division of Gastroenterology and Hepatology, University of Maryland School of Medicine, Baltimore, MD, USA
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De Cristofaro E, Montesano L, Lolli E, Biancone L, Monteleone G, Calabrese E, Zorzi F. Echopattern parameter as an aid to profile Crohn's disease patients. Dig Liver Dis 2023; 55:1652-1657. [PMID: 37258331 DOI: 10.1016/j.dld.2023.05.018] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/14/2023] [Revised: 05/03/2023] [Accepted: 05/16/2023] [Indexed: 06/02/2023]
Abstract
BACKGROUND Intestinal ultrasonography (US) allows for the characterization of the intestinal lesions and provides information on transmural inflammation. The aim of the study was to assess the clinical relevance of echopattern and correlation with Crohn's disease (CD) behavior and activity. METHODS We performed a prospective study including CD patients assessed by intestinal US. The echopattern was classified as hypoechoic, hyperechoic and stratified. Color-doppler US was also performed in the thickest segment. RESULTS One hundred CD patients were enrolled. The hypoechoic echopattern was significantly correlated with penetrating behavior (r = 0.44, p<0.0001), active disease (r = 0.21, p = 0.034), C-reactive protein/Fecal Calprotectin (r = 0.31, p = 0.004; r = 0.34, p = 0.031, respectively) and steroids (r = 0.33, p = 0.0008). Hypoechoic echopattern was associated with younger age than stratified (p = 0.046) and hyperechoic (p = 0.018) echopatterns. Bowel wall thickness was greater in the hypoechoic group than in the hyperechoic/stratified groups (p = 0.011 and p<0.0001, respectively). Hypoechoic echopattern was associated with fistulas (r = 0.52, p<0.0001) and increased vascularization (r = 0.32, p = 0.001). The hyperechoic echopattern showed a significant correlation with stricturing disease and an inverse correlation with fistulas. During a follow up period of 6 months, patients with hypoechoic echopattern had an increased risk of biological therapy need or surgery. CONCLUSIONS The characterization of bowel wall echopattern allows for the identification of different CD behaviors.
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Affiliation(s)
- Elena De Cristofaro
- Unità Operativa di Gastroenterologia, Dipartimento di Medicina, Policlinico Universitario Tor Vergata, Rome, Italy
| | - Laura Montesano
- Unità Operativa di Gastroenterologia, Dipartimento di Medicina, Policlinico Universitario Tor Vergata, Rome, Italy
| | - Elisabetta Lolli
- Unità Operativa di Gastroenterologia, Dipartimento di Medicina, Policlinico Universitario Tor Vergata, Rome, Italy
| | - Livia Biancone
- Unità Operativa di Gastroenterologia, Dipartimento di Medicina, Policlinico Universitario Tor Vergata, Rome, Italy; Cattedra di Gastroenterologia, Dipartimento di Medicina dei Sistemi, Università degli studi di Roma Tor Vergata, Italy
| | - Giovanni Monteleone
- Unità Operativa di Gastroenterologia, Dipartimento di Medicina, Policlinico Universitario Tor Vergata, Rome, Italy; Cattedra di Gastroenterologia, Dipartimento di Medicina dei Sistemi, Università degli studi di Roma Tor Vergata, Italy
| | - Emma Calabrese
- Unità Operativa di Gastroenterologia, Dipartimento di Medicina, Policlinico Universitario Tor Vergata, Rome, Italy; Cattedra di Gastroenterologia, Dipartimento di Medicina dei Sistemi, Università degli studi di Roma Tor Vergata, Italy.
| | - Francesca Zorzi
- Unità Operativa di Gastroenterologia, Dipartimento di Medicina, Policlinico Universitario Tor Vergata, Rome, Italy
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Zhang N, Chan ML, Li J, Brohawn PZ, Sun B, Vainshtein I, Roskos LK, Faggioni R, Savic RM. Combining pharmacometric models with predictive and prognostic biomarkers for precision therapy in Crohn's disease: A case study of brazikumab. CPT Pharmacometrics Syst Pharmacol 2023; 12:1945-1959. [PMID: 37691451 PMCID: PMC10725267 DOI: 10.1002/psp4.13044] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2023] [Revised: 06/11/2023] [Accepted: 07/11/2023] [Indexed: 09/12/2023] Open
Abstract
Pharmacometric models were used to investigate the utility of biomarkers in predicting the efficacy (Crohn's Disease Activity Index [CDAI]) of brazikumab and provide a data-driven framework for precision therapy for Crohn's disease (CD). In a phase IIa trial in patients with moderate to severe CD, treatment with brazikumab, an anti-interleukin 23 monoclonal antibody, was associated with clinical improvement. Brazikumab treatment effect was determined to be dependent on the baseline IL-22 (BIL22) or baseline C-reactive protein (BCRP; predictive biomarkers), and placebo effect was found to be correlated with the baseline CDAI (a prognostic biomarker). A maximal total inhibition on CDAI input function of 50.6% and 42.4% was predicted for patients with extremely high BIL22 or BCRP, compared to a maximal total inhibition of 20.9% and 17.8% for patients with extremely low BIL22 or BCRP, respectively, which were mainly due to the placebo effect. We demonstrated that model-derived baseline biomarker levels that achieve 50% of maximum unbound systemic concentration of 22.8 pg/mL and 8.03 mg/L for BIL22 and BCRP as the cutoffs to select subpopulations can effectively identify high-response subgroup patients with improved separation of responders when compared to using the median values as the cutoff. This work exemplifies the utility of pharmacometrics to quantify biomarker-driven responses in biologic therapies and distinguish between predictive and prognostic biomarkers, complementing clinical efforts of identifying subpopulations with higher likelihood of response to brazikumab.
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Affiliation(s)
- Nan Zhang
- Department of Bioengineering and Therapeutic SciencesUniversity of California San FranciscoSan FranciscoCaliforniaUSA
| | - Ming Liang Chan
- Department of Bioengineering and Therapeutic SciencesUniversity of California San FranciscoSan FranciscoCaliforniaUSA
| | - Jing Li
- Clinical Pharmacology and Quantitative Pharmacology, Clinical Pharmacology & Safety Sciences (CPSS), R&D, AstraZenecaSouth San FranciscoCaliforniaUSA
| | - Philip Z. Brohawn
- Translational Science and Experimental Medicine, Research and Early Development, Respiratory and Immunology (R&I), BioPharmaceutical R&D, AstraZenecaGaithersburgMarylandUSA
| | - Bo Sun
- Clinical Pharmacology and Quantitative Pharmacology, Clinical Pharmacology & Safety Sciences (CPSS), R&D, AstraZenecaSouth San FranciscoCaliforniaUSA
| | - Inna Vainshtein
- Clinical Pharmacology and Quantitative Pharmacology, Clinical Pharmacology & Safety Sciences (CPSS), R&D, AstraZenecaSouth San FranciscoCaliforniaUSA
| | - Lorin K. Roskos
- Clinical Pharmacology and Quantitative Pharmacology, Clinical Pharmacology & Safety Sciences (CPSS), R&D, AstraZenecaSouth San FranciscoCaliforniaUSA
| | - Raffaella Faggioni
- Clinical Pharmacology and Quantitative Pharmacology, Clinical Pharmacology & Safety Sciences (CPSS), R&D, AstraZenecaSouth San FranciscoCaliforniaUSA
| | - Rada M. Savic
- Department of Bioengineering and Therapeutic SciencesUniversity of California San FranciscoSan FranciscoCaliforniaUSA
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Sipeki N, Kovats PJ, Deutschmann C, Schierack P, Roggenbuck D, Papp M. Location-based prediction model for Crohn's disease regarding a novel serological marker, anti-chitinase 3-like 1 autoantibodies. World J Gastroenterol 2023; 29:5728-5750. [PMID: 38075846 PMCID: PMC10701337 DOI: 10.3748/wjg.v29.i42.5728] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/28/2023] [Revised: 10/03/2023] [Accepted: 11/02/2023] [Indexed: 11/13/2023] Open
Abstract
BACKGROUND Defective neutrophil regulation in inflammatory bowel disease (IBD) is thought to play an important role in the onset or manifestation of IBD, as it could lead to damage of the intestinal mucosal barrier by the infiltration of neutrophils in the inflamed mucosa and the accumulation of pathogens. Like neutrophils in the context of innate immune responses, immunoglobulin A (IgA) as an acquired immune response partakes in the defense of the intestinal epithelium. Under normal conditions, IgA contributes to the elimination of microbes, but in connection with the loss of tolerance to chitinase 3-like 1 (CHI3L1) in IBD, IgA could participate in CHI3L1-mediated improved adhesion and invasion of potentially pathogenic microorganisms. The tolerance brake to CHI3L1 and the occurrence of IgA autoantibodies to this particular target, the exact role and underlying mechanisms of CHI3L1 in the pathogenesis of IBD are still unclear. AIM To determine the predictive potential of Ig subtypes of a novel serological marker, anti-CHI3L1 autoantibodies (aCHI3L1) in determining the disease phenotype, therapeutic strategy and long-term disease course in a prospective referral cohort of adult IBD patients. METHODS Sera of 257 Crohn's disease (CD) and 180 ulcerative colitis (UC) patients from a tertiary IBD referral center of Hungary (Division of Gastroenterology, Department of Internal Medicine, Faculty of Medicine, University of Debrecen) were assayed for IgG, IgA, and secretory IgA (sIgA) type aCHI3L1 by enzyme-linked immunosorbent assay using recombinant CHI3L1, along with 86 healthy controls (HCONT). RESULTS The IgA type was more prevalent in CD than in UC (29.2% vs 11.1%) or HCONT (2.83%; P < 0.0001 for both). However, sIgA subtype aCHI3L1 positivity was higher in both CD and UC patients than in HCONT (39.3% and 32.8% vs 4.65%, respectively; P < 0.0001). The presence of both IgA and sIgA aCHI3L1 antibodies was associated with colonic involvement (P < 0.0001 and P = 0.038, respectively) in patients with CD. Complicated disease behavior at sample procurement was associated with aCHI3L1 sIgA positivity (57.1% vs 36.0%, P = 0.009). IgA type aCH3L1 was more prevalent in patients with frequent relapse during the disease course in the CD group (46.9% vs 25.7%, P = 0.005). In a group of patients with concomitant presence of pure inflammatory luminal disease and colon involvement at the time of diagnosis, positivity for IgA or sIgA type aCH3L1 predicted faster progression towards a complicated disease course in time-dependent models. This association disappeared after merging subgroups of different disease locations. CONCLUSION CHI3L1 is a novel neutrophil autoantigenic target in IBD. The consideration of antibody classes along with location-based prediction may transform the future of serology in IBD.
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Affiliation(s)
- Nora Sipeki
- Division of Gastroenterology, Department of Internal Medicine, Faculty of Medicine, University of Debrecen, Debrecen H-4032, Hungary
| | - Patricia Julianna Kovats
- Division of Gastroenterology, Department of Internal Medicine, Faculty of Medicine, University of Debrecen, Debrecen H-4032, Hungary
- Kálmán Laki Doctoral School, Faculty of Medicine, University of Debrecen, Debrecen H-4032, Hungary
| | - Claudia Deutschmann
- Institute of Biotechnology, Faculty Environment and Natural Sciences, Brandenburg University of Technology Cottbus-Senftenberg, Senftenberg 01968, Germany
| | - Peter Schierack
- Institute of Biotechnology, Faculty Environment and Natural Sciences, Brandenburg University of Technology Cottbus-Senftenberg, Senftenberg 01968, Germany
- Faculty of Health Sciences Brandenburg, Brandenburg University of Technology Cottbus-Senftenberg, Senftenberg 01968, Germany
| | - Dirk Roggenbuck
- Institute of Biotechnology, Faculty Environment and Natural Sciences, Brandenburg University of Technology Cottbus-Senftenberg, Senftenberg 01968, Germany
- Faculty of Health Sciences Brandenburg, Brandenburg University of Technology Cottbus-Senftenberg, Senftenberg 01968, Germany
- Medipan GmbH & GA Generic Assays GmbH, Dahlewitz-Berlin 15827, Germany
| | - Maria Papp
- Division of Gastroenterology, Department of Internal Medicine, Faculty of Medicine, University of Debrecen, Debrecen H-4032, Hungary
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Pasternak G, Chrzanowski G, Aebisher D, Myśliwiec A, Dynarowicz K, Bartusik-Aebisher D, Sosna B, Cieślar G, Kawczyk-Krupka A, Filip R. Crohn's Disease: Basic Characteristics of the Disease, Diagnostic Methods, the Role of Biomarkers, and Analysis of Metalloproteinases: A Review. Life (Basel) 2023; 13:2062. [PMID: 37895443 PMCID: PMC10608618 DOI: 10.3390/life13102062] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2023] [Revised: 10/10/2023] [Accepted: 10/12/2023] [Indexed: 10/29/2023] Open
Abstract
Crohn's disease is a chronic inflammatory bowel disease that affects the ileum and/or large intestine. At the same time, it can also affect any other part of the human body, i.e., from the mouth to the anus. In Crohn's disease, the physiology and functioning of the epithelial barrier are inhibited due to the correlation of various factors, such as the environment, genetic susceptibility or intestinal microbiota. The symptoms are very troublesome and cause a significant reduction in quality of life, sometimes occurring with paralyzing permanent damage to the digestive tract, requiring enteral or parenteral nutrition throughout life. In order to make a proper and accurate diagnosis, an appropriately selected diagnostic path in a given clinical entity is necessary. Standard diagnostic methods are: laboratory examination, histopathological examination, endoscopic examination, X-ray, computed tomography, ultrasound examination and magnetic resonance imaging. Medical biology and the analysis of metalloproteinases have also proved helpful in diagnosing changes occurring as a result of Crohn's disease. Here we provide a thorough review of the latest reports on Crohn's disease and its genetic conditions, symptoms, morphology, diagnosis (including the analysis of Crohn's disease biomarkers, i.e., metalloproteinases) and treatment.
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Affiliation(s)
- Grzegorz Pasternak
- Department of General Surgery, Provincial Clinical Hospital No. 2 in Rzeszów, 35-301 Rzeszów, Poland;
| | - Grzegorz Chrzanowski
- Department of Biology, College of Natural Sciences, University of Rzeszów, 35-310 Rzeszów, Poland
| | - David Aebisher
- Department of Photomedicine and Physical Chemistry, Medical College, University of Rzeszów, 35-310 Rzeszów, Poland
| | - Angelika Myśliwiec
- Center for Innovative Research in Medical and Natural Sciences, Medical College, University of Rzeszów, 35-310 Rzeszów, Poland; (A.M.); (K.D.)
| | - Klaudia Dynarowicz
- Center for Innovative Research in Medical and Natural Sciences, Medical College, University of Rzeszów, 35-310 Rzeszów, Poland; (A.M.); (K.D.)
| | - Dorota Bartusik-Aebisher
- Department of Biochemistry and General Chemistry, Medical College, University of Rzeszów, 35-310 Rzeszów, Poland;
| | - Barbara Sosna
- Department of Internal Medicine, Angiology and Physical Medicine, Center for Laser Diagnostics and Therapy, Medical University of Silesia in Katowice, Batorego 15 Street, 41-902 Bytom, Poland; (B.S.); (G.C.); (A.K.-K.)
| | - Grzegorz Cieślar
- Department of Internal Medicine, Angiology and Physical Medicine, Center for Laser Diagnostics and Therapy, Medical University of Silesia in Katowice, Batorego 15 Street, 41-902 Bytom, Poland; (B.S.); (G.C.); (A.K.-K.)
| | - Aleksandra Kawczyk-Krupka
- Department of Internal Medicine, Angiology and Physical Medicine, Center for Laser Diagnostics and Therapy, Medical University of Silesia in Katowice, Batorego 15 Street, 41-902 Bytom, Poland; (B.S.); (G.C.); (A.K.-K.)
| | - Rafał Filip
- Department of Internal Medicine, Medical College, University of Rzeszów, 35-310 Rzeszów, Poland;
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Vera Chamorro JF, Sánchez Franco C, Vargas Sandoval M, Mora Quintero DV, Riveros López JP, Sarmiento Quintero F, Ortiz-Piedrahita C, Calderón-Guerrero OG, Laignelet H, Losada Gómez CL, Sánchez DP, López Panqueva RDP, Aponte Barrios W, Triana Rodríguez GA, Osorno A, Becerra Granados LM, Ortega López MC, Correa Jiménez Ó, Maradei Anaya SJ, García Acero M, Acevedo Forero AM, Prada A, Ramírez Urrego LC, Salcedo Castilla LK, Enríquez A, Suárez Fuentes MA, González Leal N, Peña Hernández S, Sotaquirá Guáqueta L, Sosa F, Fierro F, Correa S, Martín de Carpi FJ. Consenso colombiano de la enfermedad inflamatoria intestinal pediátrica. REVISTA COLOMBIANA DE GASTROENTEROLOGÍA 2023; 38:1-75. [DOI: 10.22516/25007440.943] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
Abstract
Introducción: la colitis ulcerativa pediátrica (CUP), la enfermedad de Crohn pediátrica (ECP) y la enfermedad inflamatoria intestinal pediátrica no clasificable (EIIPNC) tienen particularidades clínicas y psicosociales que las diferencian de las del adulto y pueden condicionar enfoques terapéuticos distintos por las posibles repercusiones nutricionales, crecimiento y desarrollo, lo que representa un desafío para el pediatra y el gastroenterólogo. Objetivo: desarrollar recomendaciones basadas en la evidencia por consenso de expertos para el diagnóstico y el tratamiento oportunos y seguros de la enfermedad inflamatoria intestinal pediátrica (EIIP) en menores de 18 años, para los profesionales que atienden estos pacientes y los pagadores en salud. Metodología: a través de un panel de expertos del Colegio Colombiano de Gastroenterología, Hepatología y Nutrición Pediátrica (COLGAHNP) y un grupo multidisciplinario se formularon 35 preguntas en relación con el cuadro clínico, el diagnóstico y el tratamiento de la EIIP. A través de una revisión y un análisis crítico de la literatura, con especial énfasis en las principales guías de práctica clínica (GPC), estudios clínicos aleatorizados (ECA) y metaanálisis de los últimos 10 años, los expertos plantearon 77 recomendaciones que respondían a cada una de las preguntas de investigación con sus respectivos puntos prácticos. Posteriormente, cada una de las afirmaciones se sometieron a votación dentro del grupo desarrollador, incluyendo las afirmaciones que alcanzaron > 80 %. Resultados: todas las afirmaciones alcanzaron una votación > 80 %. La EIIP tiene mayor extensión, severidad y evolución hacia la estenosis, enfermedad perianal, manifestaciones extraintestinales y retraso en el crecimiento en comparación con los pacientes adultos, por lo que su manejo debe ser realizado por grupos multidisciplinarios liderados por gastroenterólogos pediatras y prepararlos para una transición a la edad adulta. Los criterios de Porto permiten una clasificación práctica de la EIIP. En la ECP, debemos usar la clasificación de París y debemos realizar ileocolonoscopia y esofagogastroduodenoscopia, ya que el 50 % tienen un compromiso superior, usando el SES-CD (UCEIS/Mayo en CUP) y tomando múltiples biopsias. Los laboratorios iniciales deben incluir marcadores de inflamación, calprotectina fecal y descartar infecciones intestinales. El tratamiento, la inducción y el mantenimiento de la EIIP deben ser individualizados y decididos según la estratificación de riesgo. En el seguimiento se debe usar el Pediatric Crohn Disease Activity Index (PCDAI) y Pediatric Ulcerative Colitis Activity Index (PUCAI) de las últimas 48 horas. Los pacientes con EIIP temprana e infantil, deben ser valorados por inmunólogos y genetistas. Conclusión: se proporciona una guía de consenso con recomendaciones basadas en la evidencia sobre el diagnóstico y los tratamientos oportunos y seguros en los pacientes con EIIP.
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Ullah H, Deng T, Ali M, Farooqui NA, Alsholi DM, Siddiqui NZ, Rehman AU, Ali S, Ilyas M, Wang L, Xin Y. Sea Conch Peptides Hydrolysate Alleviates DSS-Induced Colitis in Mice through Immune Modulation and Gut Microbiota Restoration. Molecules 2023; 28:6849. [PMID: 37836692 PMCID: PMC10574497 DOI: 10.3390/molecules28196849] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2023] [Revised: 09/12/2023] [Accepted: 09/15/2023] [Indexed: 10/15/2023] Open
Abstract
Inflammatory bowel disease (IBD) is a persistent, lifelong inflammation of the digestive system. Dextran sulfate sodium is commonly used to induce colitis in experimental animal models, which causes epithelial damage, intestinal inflammation, mucin depletion, and dysbiosis of the gut microbiota. Various prebiotics, polysaccharides, and polypeptides are used for IBD treatment. In this study, we used a murine model utilizing BALB/c mice, with 10 mice per group, to investigate the treatment effect of sea conch peptide hydrolysate (CPH) on DSS-induced colitis mice. Colitis was induced through the administration of 2.5% DSS in drinking water over a seven-days period. Furthermore, on the eighth day of the experiment, sea conch peptide hydrolysate (CPH) at low (100 mg/kg), medium (200 mg/kg), and high (400 mg/kg) doses, which were continued for 14 days, were assessed for medicinal purposes in DSS-induced colitis mice. Our results showed that CPH treatment significantly alleviated the severity and symptoms of colitis. The epithelial integrity and histological damage were improved. Intestinal inflammation and inflammatory cell infiltration were improved. Furthermore, the expression of pro-inflammatory cytokines was reduced, and intestinal barrier integrity was restored by elevating the tight junction proteins. Moreover, 16s RNA sequencing revealed dysbiosis of the gut microbiota was observed upon DSS treatment, which was reinstated after CPH treatment. An increased level of Firmicutes and Lactobacillus was observed in the treatment groups. Finally, our results suggest that CPH would be recommended as a functional food source and also have the potential to be used as a medicinal product for different gastrointestinal disorders.
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Affiliation(s)
- Hidayat Ullah
- Department of Biotechnology, College of Basic Medical Science, Dalian Medical University, Dalian 116044, China; (H.U.); (T.D.); (M.A.); (N.A.F.); (D.M.A.); (N.Z.S.); (A.U.R.); (M.I.)
| | - Ting Deng
- Department of Biotechnology, College of Basic Medical Science, Dalian Medical University, Dalian 116044, China; (H.U.); (T.D.); (M.A.); (N.A.F.); (D.M.A.); (N.Z.S.); (A.U.R.); (M.I.)
| | - Muhsin Ali
- Department of Biotechnology, College of Basic Medical Science, Dalian Medical University, Dalian 116044, China; (H.U.); (T.D.); (M.A.); (N.A.F.); (D.M.A.); (N.Z.S.); (A.U.R.); (M.I.)
| | - Nabeel Ahmed Farooqui
- Department of Biotechnology, College of Basic Medical Science, Dalian Medical University, Dalian 116044, China; (H.U.); (T.D.); (M.A.); (N.A.F.); (D.M.A.); (N.Z.S.); (A.U.R.); (M.I.)
| | - Duaa M. Alsholi
- Department of Biotechnology, College of Basic Medical Science, Dalian Medical University, Dalian 116044, China; (H.U.); (T.D.); (M.A.); (N.A.F.); (D.M.A.); (N.Z.S.); (A.U.R.); (M.I.)
| | - Nimra Zafar Siddiqui
- Department of Biotechnology, College of Basic Medical Science, Dalian Medical University, Dalian 116044, China; (H.U.); (T.D.); (M.A.); (N.A.F.); (D.M.A.); (N.Z.S.); (A.U.R.); (M.I.)
| | - Ata Ur Rehman
- Department of Biotechnology, College of Basic Medical Science, Dalian Medical University, Dalian 116044, China; (H.U.); (T.D.); (M.A.); (N.A.F.); (D.M.A.); (N.Z.S.); (A.U.R.); (M.I.)
| | - Sharafat Ali
- Department of Biochemistry and Molecular Biology, College of Basic Medical Science, Dalian Medical University, Dalian 116044, China;
| | - Muhammad Ilyas
- Department of Biotechnology, College of Basic Medical Science, Dalian Medical University, Dalian 116044, China; (H.U.); (T.D.); (M.A.); (N.A.F.); (D.M.A.); (N.Z.S.); (A.U.R.); (M.I.)
| | - Liang Wang
- Stem Cell Clinical Research Center, National Joint Engineering Laboratory, Regenerative Medicine Center, The First Affiliated Hospital of Dalian Medical University, Dalian 116011, China
| | - Yi Xin
- Department of Biotechnology, College of Basic Medical Science, Dalian Medical University, Dalian 116044, China; (H.U.); (T.D.); (M.A.); (N.A.F.); (D.M.A.); (N.Z.S.); (A.U.R.); (M.I.)
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Shelygin YA, Ivashkin VT, Achkasov SI, Reshetov IV, Maev IV, Belousova EA, Vardanyan AV, Nanaeva BA, Adamyan LV, Drapkina OM, Namazova-Baranova LS, Razumovsky AY, Revishvili AS, Khatkov IE, Shabunin AV, Livzan MA, Sazhin AV, Timerbulatov VM, Khlynova OV, Abdulganieva DI, Abdulkhakov RA, Aleksandrov TL, Alekseeva OP, Alekseenko SA, Anosov IS, Bakulin IG, Barysheva OY, Bolikhov KV, Veselov VV, Golovenko OV, Gubonina IV, Dolgushina AI, Zhigalova TN, Kagramanova AV, Kashnikov VN, Knyazev OV, Kostenko NV, Likutov AA, Lomakina EY, Loranskaya ID, Mingazov AF, Moskalev AI, Nazarov IV, Nikitina NV, Odintsova AH, Omelyanovsky VV, Osipenko MF, Оshchepkov АV, Pavlenko VV, Poluektova EA, Rodoman GV, Segal AM, Sitkin SI, Skalinskaya MI, Surkov AN, Sushkov OI, Tarasova LV, Uspenskaya YB, Frolov SA, Chashkova EY, Shifrin OS, Shcherbakova OV, Shchukina OB, Shkurko TV, Makarchuk PA. Clinical guidelines. Crohn’s disease (К50), adults. KOLOPROKTOLOGIA 2023; 22:10-49. [DOI: 10.33878/2073-7556-2023-22-3-10-49] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 09/17/2024]
Affiliation(s)
- Yury A. Shelygin
- Ryzhikh National Medical Research Center of Coloproctology; Russian Medical Academy of Continuous Professional Education
| | | | - Sergey I. Achkasov
- Ryzhikh National Medical Research Center of Coloproctology; Russian Medical Academy of Continuous Professional Education
| | - Igor V. Reshetov
- I.M. Sechenov First Moscow State Medical University (Sechenov University)
| | - Igor V. Maev
- Moscow State University of Medicine and Dentistry named after A.I. Evdokimov
| | | | | | | | - Leila V. Adamyan
- Moscow State University of Medicine and Dentistry named after A.I. Evdokimov; Mational Medical Research Center of Obstetrics and Gynecology named after V.I. Kulakov
| | - Oksana M. Drapkina
- Moscow State University of Medicine and Dentistry named after A.I. Evdokimov; National Medical Research Center for Therapy and Preventive Medicine
| | - Leila S. Namazova-Baranova
- Reseach Instinute of Pediatrics and Child Health Protection of the Central Clinical Hospital of the Russian Academy of Sciences
| | | | - Amiran Sh. Revishvili
- A.V. Vishnevsky National Medical Research Center of Surgery; Russian Medical Academy of Continuous Professional Education
| | - Igor E. Khatkov
- Moscow Clinical/research Center named after A.S. Loginov" of the Moscow Department of Health
| | | | | | | | | | - Olga V. Khlynova
- Perm State Medical University named after Academician E.A. Wagner" of the Ministry of Health of Russia
| | | | | | | | - Olga P. Alekseeva
- Nizhny Novgorod Regional Clinical Hospital named after N.A. Semashko
| | | | - Ivan S. Anosov
- Ryzhikh National Medical Research Center of Coloproctology
| | - Igor G. Bakulin
- I.I. Mechnikov Northwestern State Medical University of the Ministry of Health of Russia
| | - Olga Yu. Barysheva
- Petrozavodsk State University of the Ministry of Education and Science of Russia
| | | | - Viktor V. Veselov
- Ryzhikh National Medical Research Center of Coloproctology; Russian Medical Academy of Continuous Professional Education
| | | | | | | | | | - Anna V. Kagramanova
- Moscow Clinical/research Center named after A.S. Loginov" of the Moscow Department of Health
| | | | - Oleg V. Knyazev
- Moscow Clinical/research Center named after A.S. Loginov" of the Moscow Department of Health
| | | | | | | | | | | | | | | | | | - Alfia H. Odintsova
- Clinical Hospital of the Ministry of Health of the Republic of Tatarstan
| | | | | | | | | | | | | | | | - Stanislav I. Sitkin
- I.I. Mechnikov Northwestern State Medical University of the Ministry of Health of Russia
| | - Maria I. Skalinskaya
- I.I. Mechnikov Northwestern State Medical University of the Ministry of Health of Russia
| | - Andrey N. Surkov
- Reseach Instinute of Pediatrics and Child Health Protection of the Central Clinical Hospital of the Russian Academy of Sciences
| | | | | | | | | | | | - Oleg S. Shifrin
- I.M. Sechenov First Moscow State Medical University (Sechenov University)
| | | | - Oksana B. Shchukina
- First St. Petersburg State Medical University named after Academician I.P. Pavlov
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Zhou S, Yu J. Crohn's disease and breast cancer: a literature review of the mechanisms and treatment. Intern Emerg Med 2023; 18:1303-1316. [PMID: 37138170 PMCID: PMC10412481 DOI: 10.1007/s11739-023-03281-0] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/20/2023] [Accepted: 04/14/2023] [Indexed: 05/05/2023]
Abstract
This is a literature review describes Crohn's disease (CD) concomitant with breast cancer and summarizes possible common pathogenic mechanisms shared by the two diseases involving the IL-17 and NF-κB signaling pathways. Inflammatory cytokines including TNF-α and Th17 cells in CD patients can induce activation of the ERK1/2, NF-κB and Bcl-2 pathways. Hub genes are involved in the generation of cancer stem cells (CSCs) and are related to inflammatory mediators, including CXCL8, IL1-β and PTGS2, which promote inflammation and breast cancer growth, metastasis, and development. CD activity is highly associated with altered intestinal microbiota processes, including secretion of complex glucose polysaccharides by Ruminococcus gnavus colonies; furthermore, γ-proteobacteria and Clostridium are associated with CD recurrence and active CD, while Ruminococcaceae, Faecococcus and Vibrio desulfuris are associated with CD remission. Intestinal microbiota disorder promotes breast cancer occurrence and development. Bacteroides fragilis can produce toxins that induce breast epithelial hyperplasia and breast cancer growth and metastasis. Gut microbiota regulation can also improve chemotherapy and immunotherapy efficacy in breast cancer treatment. Intestinal inflammation can affects the brain through the brain-gut axis, which activates the hypothalamic‒pituitary‒adrenal (HPA) axis to induce anxiety and depression in patients; these effects can inhibit the antitumor immune responses of the immune system and promote breast cancer occurrence in patients with CD. There are few studies on the treatment of patients with CD concomitant with breast cancer, but published studies show three main strategies: new biological agents combined with breast cancer treatment methods, intestinal fecal bacteria transplantation, and dietary treatment.
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Affiliation(s)
- Sisi Zhou
- Department of Gastroenterology, First Affiliated Hospital of Shantou University Medical College, Shantou, 515041, Guangdong Province, China
| | - Jing Yu
- Department of Gastroenterology, First Affiliated Hospital of Shantou University Medical College, Shantou, 515041, Guangdong Province, China.
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Lee HH, Gweon TG, Kang SG, Jung SH, Lee KM, Kang SB. Assessment of Fatigue and Associated Factors in Patients with Inflammatory Bowel Disease: A Questionnaire-Based Study. J Clin Med 2023; 12:jcm12093116. [PMID: 37176558 PMCID: PMC10179196 DOI: 10.3390/jcm12093116] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2023] [Revised: 04/16/2023] [Accepted: 04/23/2023] [Indexed: 05/15/2023] Open
Abstract
Although fatigue is common in patients with inflammatory bowel disease (IBD), it often goes unrecognized and untreated. We investigated the degree of fatigue and associated factors in patients with IBD. A multicenter study involving 147 IBD patients was conducted at five academic hospitals from August 2019 to December 2021. Fatigue was evaluated using the validated Korean version of the Multidimensional Fatigue Inventory (MFI-K). Among 97 ulcerative colitis patients and 50 Crohn's disease patients, the mean total MFI-K score was 59.0 ± 5.5, which corresponded to a moderate-to-severe level of fatigue. Moderate-to-severe disease activity was found to be significantly associated with a higher general and physical fatigue subscale MFI-K score compared to remission-to-mild disease activity (17.6 ± 1.7 vs. 16.7 ± 2.0, p = 0.009), while the use of biologics was associated with a lower total MFI-K score (57.3 ± 5.0 vs. 59.5 ± 5.5, p = 0.031). In multiple linear regression, the total MFI-K score was positively correlated with a history of surgery for IBD, while it was negatively correlated with the use of biologics. Depression was positively correlated with the reduced motivation subscale score. The degree of fatigue in patients with IBD was high. Disease activity, the use of biologics, a history of surgery for IBD, and depression were associated with fatigue.
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Affiliation(s)
- Han Hee Lee
- Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea
| | - Tae-Geun Gweon
- Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea
| | - Sung-Goo Kang
- Department of Family Medicine, St. Vincent's Hospital, College of Medicine, The Catholic University of Korea, Seoul 16247, Republic of Korea
| | - Sung Hoon Jung
- Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea
| | - Kang-Moon Lee
- Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea
| | - Sang-Bum Kang
- Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea
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Kridin K, Goral D, Shihade W, Tzur-Bitan D, Onn E, Zoller L, Cohen AD. Vitiligo and Crohn's disease form an autoimmune cluster: insights from a population-based study. Scand J Gastroenterol 2023; 58:354-359. [PMID: 36222357 DOI: 10.1080/00365521.2022.2131332] [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] [Indexed: 02/04/2023]
Abstract
BACKGROUND While the coexistence of vitiligo and Crohn's disease (CD) has been reported in individual patients, the epidemiological association between these autoimmune conditions remains inconclusive. OBJECTIVE To assess the bidirectional association between vitiligo and CD. METHODS A population-based study was performed to compare vitiligo patients (n = 20,851) with age-, sex- and ethnicity-matched control subjects (n = 102,475) regarding the incidence of new-onset and the prevalence of preexisting CD. Adjusted hazard ratios (HRs) and adjusted odds ratios (ORs) were calculated by multivariable Cox regression and logistic regression, respectively. RESULTS The incidence rate of new-onset CD was evaluated at 3.6 (95% CI, 2.7-4.9) cases per 10,000 person-years (PY) in patients with vitiligo and 2.4 (95% CI, 2.0-2.9) cases per 10,000 PY in controls. Patients with vitiligo experienced an elevated risk of CD (fully adjusted HR, 1.60; 95% CI, 1.10-2.34; p = 0.015). Congruently, a history of preexisting CD predicted elevated odds of having subsequent vitiligo (fully adjusted OR, 1.49; 95% CI, 1.15-1.93; p = 0.002). Compared to other patients with vitiligo, those with vitiligo and comorbid CD were older and had a higher prevalence of diabetes mellitus, hyperlipidemia, and hypertension but a comparable all-cause mortality rate. CONCLUSIONS The current study depicts a robust bidirectional association between vitiligo and CD. This knowledge is of clinical implication for physicians managing patients with both conditions. The diagnostic threshold for CD should be lowered in vitiligo patients with compatible symptoms.
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Affiliation(s)
- Khalaf Kridin
- Unit of Dermatology and Skin Research Laboratory, Baruch Padeh Medical Center, Poriya, Israel
- Azrieli Faculty of Medicine, Bar-Ilan University, Safed, Israel
- Lübeck Institute of Experimental Dermatology, University of Lübeck, Lübeck, Germany
| | - Daniel Goral
- Azrieli Faculty of Medicine, Bar-Ilan University, Safed, Israel
| | - Wesal Shihade
- School of Public Health, University of Haifa, Haifa, Israel
| | - Dana Tzur-Bitan
- Department of Behavioral Sciences, Ariel University, Ariel, Israel
- Shalvata Mental Health Center, Hod Hasharon, affiliated with the Sackler School of Medicine, Tel Aviv University, Ramat Aviv, Israel
| | - Erez Onn
- Azrieli Faculty of Medicine, Bar-Ilan University, Safed, Israel
- Baruch Padeh Medical Center, Poriya, Israel
| | | | - Arnon D Cohen
- Clalit Health Services, Tel-Aviv and Haifa, Israel
- Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel
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Chappe C, Salut C, Amiot A, Gaye D, Frulio N, Lapuyade B, Vuitton L, Altwegg R, Gilletta C, Fumery M, Bouguen G, Serrero M, Nachury M, de Suray N, Caillo L, Simon M, Laharie D, Rivière P, Poullenot F. Preoperative Predictors of Neoplasia in Patients Undergoing Small Bowel Resection for Complicated Crohn’s Disease: A Multicentre Case-Control Study. Cancers (Basel) 2023; 15:cancers15072004. [PMID: 37046666 PMCID: PMC10093720 DOI: 10.3390/cancers15072004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2023] [Revised: 03/24/2023] [Accepted: 03/24/2023] [Indexed: 03/30/2023] Open
Abstract
Crohn’s disease (CD) is associated with an increased risk of small bowel neoplasia (SBN). We aimed to assess preoperative predictors of SBN in CD patients. We conducted a retrospective case-control study including CD patients who underwent surgery: cases were diagnosed with SBN on histopathological analysis and controls had no neoplasia. Preoperative cross-sectional imaging was reviewed by a panel of blinded expert radiologists. Fifty cases were matched to one hundred and fifty consecutive controls. In multivariable analysis, predictors of SBN were age ≥ 50 years (OR = 28, 95% CI = 5.05–206), median CD duration ≥ 17.5 years (OR = 4.25, 95% CI = 1.33–14.3), and surgery for stricture (OR = 5.84, 95% CI = 1.27–35.4). The predictors of small bowel adenocarcinoma were age ≥ 50 years (OR = 5.14, 95% CI = 2.12–12.7), CD duration ≥ 15 years (OR = 5.65, 95% CI = 2.33–14.3), and digestive wall thickening > 8 mm (OR = 3.79, 95% CI = 1.45–11.3). A predictive score based on the aforementioned factors was constructed. Almost 73.7% of patients with a high score had SBA. Old age, long small bowel CD duration, and stricture predicted the presence of SBN, particularly adenocarcinoma when patients have digestive wall thickening > 8 mm on preoperative imaging.
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Boronat-Toscano A, Vañó I, Monfort-Ferré D, Menacho M, Valldosera G, Caro A, Espina B, Mañas MJ, Marti M, Espin E, Saera-Vila A, Serena C. Smoking Suppresses the Therapeutic Potential of Adipose Stem Cells in Crohn’s Disease Patients through Epigenetic Changes. Cells 2023; 12:cells12071021. [PMID: 37048094 PMCID: PMC10093550 DOI: 10.3390/cells12071021] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2023] [Revised: 03/21/2023] [Accepted: 03/25/2023] [Indexed: 03/29/2023] Open
Abstract
Patients with Crohn’s disease (CD) who smoke are known to have a worse prognosis than never-smokers and a higher risk for post-surgical recurrence, whereas patients who quit smoking after surgery have significantly lower post-operative recurrence. The hypothesis was that smoking induces epigenetic changes that impair the capacity of adipose stem cells (ASCs) to suppress the immune system. It was also questioned whether this impairment remains in ex-smokers with CD. ASCs were isolated from non-smokers, smokers and ex-smokers with CD and their interactions with immune cells were studied. The ASCs from both smokers and ex-smokers promoted macrophage polarization to an M1 pro-inflammatory phenotype, were not able to inhibit T- and B-cell proliferation in vitro and enhanced the gene and protein expression of inflammatory markers including interleukin-1b. Genome-wide epigenetic analysis using two different bioinformatic approaches revealed significant changes in the methylation patterns of genes that are critical for wound healing, immune and metabolic response and p53-mediated DNA damage response in ASCs from smokers and ex-smokers with CD. In conclusion, cigarette smoking induces a pro-inflammatory epigenetic signature in ASCs that likely compromises their therapeutic potential.
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Bischoff SC, Bager P, Escher J, Forbes A, Hébuterne X, Hvas CL, Joly F, Klek S, Krznaric Z, Ockenga J, Schneider S, Shamir R, Stardelova K, Bender DV, Wierdsma N, Weimann A. ESPEN guideline on Clinical Nutrition in inflammatory bowel disease. Clin Nutr 2023; 42:352-379. [PMID: 36739756 DOI: 10.1016/j.clnu.2022.12.004] [Citation(s) in RCA: 103] [Impact Index Per Article: 51.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2022] [Accepted: 12/05/2022] [Indexed: 01/15/2023]
Abstract
The present guideline is an update and extension of the ESPEN scientific guideline on Clinical Nutrition in Inflammatory Bowel Disease published first in 2017. The guideline has been rearranged according to the ESPEN practical guideline on Clinical Nutrition in Inflammatory Bowel Disease published in 2020. All recommendations have been checked and, if needed, revised based on new literature, before they underwent the ESPEN consensus procedure. Moreover, a new chapter on microbiota modulation as a new option in IBD treatment has been added. The number of recommendations has been increased to 71 recommendations in the guideline update. The guideline is aimed at professionals working in clinical practice, either in hospitals or in outpatient medicine, and treating patients with IBD. General aspects of care in patients with IBD, and specific aspects during active disease and in remission are addressed. All recommendations are equipped with evidence grades, consensus rates, short commentaries and links to cited literature.
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Affiliation(s)
- Stephan C Bischoff
- Institute of Nutritional Medicine, University of Hohenheim, Stuttgart, Germany.
| | - Palle Bager
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark.
| | - Johanna Escher
- Erasmus Medical Center-Sophia Children's Hospital, Rotterdam, the Netherlands.
| | - Alastair Forbes
- Institute of Clinical Medicine, University of Tartu, Tartu, Estonia.
| | - Xavier Hébuterne
- Department of Gastroenterology and Clinical Nutrition, CHU of Nice, University Côte d'Azur, Nice, France.
| | - Christian Lodberg Hvas
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark.
| | - Francisca Joly
- Department of Gastroenterology and Nutrition Support, CHU de Beaujon, APHP, University of Paris, Paris, France.
| | - Stansilaw Klek
- Surgical Oncology Clinic, Maria Sklodowska-Curie National Cancer Institute, Krakow, Poland.
| | - Zeljko Krznaric
- Department of Gastroenterology, Hepatology and Nutrition, University Hospital Centre Zagreb, University of Zagreb, Croatia.
| | - Johann Ockenga
- Medizinische Klinik II, Klinikum Bremen-Mitte, Bremen FRG, Bremen, Germany.
| | - Stéphane Schneider
- Department of Gastroenterology and Clinical Nutrition, CHU de Nice, University Côte d'Azur, Nice, France.
| | - Raanan Shamir
- Institute for Gastroenterology, Nutrition and Liver Diseases, Schneider Children's Medical Center of Israel, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
| | - Kalina Stardelova
- University Clinic for Gastroenterohepatology, Clinical Campus "Mother Theresa", University St Cyrul and Methodius, Skopje, North Macedonia.
| | - Darija Vranesic Bender
- Unit of Clinical Nutrition, Department of Internal Medicine, University Hospital Centre Zagreb, Zagreb, Croatia.
| | - Nicolette Wierdsma
- Department of Nutrition and Dietetics, Amsterdam University Medical Centers, Amsterdam, the Netherlands.
| | - Arved Weimann
- Department of General, Visceral and Oncological Surgery, St. George Hospital, Leipzig, Germany.
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Percutaneous Drainage vs. Surgery as Definitive Treatment for Anastomotic Leak after Intestinal Resection in Patients with Crohn's Disease. J Clin Med 2023; 12:jcm12041392. [PMID: 36835926 PMCID: PMC9961459 DOI: 10.3390/jcm12041392] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2022] [Revised: 02/06/2023] [Accepted: 02/07/2023] [Indexed: 02/12/2023] Open
Abstract
BACKGROUND Anastomotic leak (AL) remains one of the most relevant complications after intestinal resection for Crohn's disease (CD). While surgery has always been considered the standard treatment for perianastomotic collection, percutaneous drainage (PD) has been proposed as a potential alternative. METHODS Retrospective study in consecutive patients treated with either PD or surgery for AL after intestinal resection for CD between 2004 and 2022. AL was defined as a perianastomotic fluid collection confirmed by radiological findings. Patients with generalized peritonitis or clinical instability were excluded. PRIMARY AIM To compare the success rate of PD vs. surgery. Secondary aims: To compare the outcomes at 90 days after the procedures; to identify the variables associated with the indication for PD. RESULTS A total of 47 patients were included, of which 25 (53%) underwent PD and 22 (47%) surgery. The success rate was 84% in the PD and 95% in the surgery group (p = 0.20). There were no significant differences between the PD and surgery group in postoperative medical and surgical complications, discharge, readmission or reoperation rates at 90 days. PD was more likely to be performed in patients with later diagnosis of AL (OR 1.25, 95% CI 1.03-1.53, p = 0.027), undergoing ileo-colic anastomosis alone (OR 3.72, 95% CI 2.29-12.45, p = 0.034) and treated after 2016 (OR 6.36, 95% CI 1.04-39.03, p = 0.046). CONCLUSION The present study suggests that PD is a safe and effective procedure to treat anastomotic leak and perianastomotic collection in CD patients. PD should be indicated in all eligible patients as an effective alternative to surgery.
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Han DY, You MW, Oh CH, Park SJ. Related Factors for Unfavorable Disease Course in Patients with Crohn's Disease: An Observational Retrospective Study. Diagnostics (Basel) 2023; 13:273. [PMID: 36673083 PMCID: PMC9857483 DOI: 10.3390/diagnostics13020273] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2022] [Revised: 01/08/2023] [Accepted: 01/08/2023] [Indexed: 01/12/2023] Open
Abstract
Background: Crohn’s disease (CD) manifests a heterogeneous clinical spectrum and disease course, and it is challenging to predict the disease outcome based on initial presentation. Objective: To analyze the long-term disease course and factors leading to poor prognosis of CD. Methods: In total, 112 patients with CD who were initially diagnosed and treated at our institution from January 2009 to August 2020 were included. We analyzed their clinical data, disease characteristics according to the Montreal classification, and the endoscopic and computed tomography (CT) examinations at the initial visit and at 2-year, 5-year, and last follow ups. We categorized the disease course into the following four categories: remission, stable, chronic refractory, and chronic relapsing. Significant factors associated with a poorer prognosis were analyzed. Results: The median follow-up period was 107 (range, 61−139) months. Complicated disease behavior increased slightly over the follow-up period (20.5% to 26.2%). An unfavorable disease course was defined as chronic refractory (19.6%) and relapsing (16.1%) courses. The 2-year disease characteristics were significant factors for unfavorable disease course, and the combination of 2-year perianal disease and 2-year moderate-to-severe CT activity could predict unfavorable disease course with the highest accuracy (0.722; area under the curve: 0.768; p < 0.0001). Conclusions: One-third of the patients with CD showed an unfavorable disease course (35.7%), and 2-year disease characteristics were significant factors for an unfavorable disease course.
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Affiliation(s)
- Dong Yoon Han
- Department of Radiology, Kyung Hee University College of Medicine, Kyung Hee University Hospital, Seoul 02447, Republic of Korea
| | - Myung-Won You
- Department of Radiology, Kyung Hee University College of Medicine, Kyung Hee University Hospital, Seoul 02447, Republic of Korea
| | - Chi Hyuk Oh
- Department of Internal Medicine, Kyung Hee University College of Medicine, Kyung Hee University Hospital, Seoul 02447, Republic of Korea
| | - Seong Jin Park
- Department of Radiology, Kyung Hee University College of Medicine, Kyung Hee University Hospital, Seoul 02447, Republic of Korea
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Wu EH, Guo Z, Zhu WM. Postoperative diarrhea in Crohn’s disease: Pathogenesis, diagnosis, and therapy. World J Clin Cases 2023; 11:7-16. [PMID: 36687182 PMCID: PMC9846968 DOI: 10.12998/wjcc.v11.i1.7] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/13/2022] [Revised: 12/08/2022] [Accepted: 12/23/2022] [Indexed: 01/04/2023] Open
Abstract
Diarrhea is a frequent symptom in postoperative patients with Crohn’s diseases (CD), and several different mechanisms likely account for postoperative diarrhea in CD. A targeted strategy based on a comprehensive understanding of postoperative diarrhea is helpful for better postoperative recovery.
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Affiliation(s)
- En-Hao Wu
- Department of General Surgery, Affiliated Jinling Hospital, Medical School of Nanjing University, Nanjing 210002, Jiangsu Province, China
| | - Zhen Guo
- Department of General Surgery, Affiliated Jinling Hospital, Medical School of Nanjing University, Nanjing 210002, Jiangsu Province, China
| | - Wei-Ming Zhu
- Department of General Surgery, Affiliated Jinling Hospital, Medical School of Nanjing University, Nanjing 210002, Jiangsu Province, China
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Koh SJ, Hong SN, Park SK, Ye BD, Kim KO, Shin JE, Yoon YS, Lee HS, Jung SH, Choi M, Na SY, Choi CH, Kim JS. Korean clinical practice guidelines on biologics for moderate to severe Crohn's disease. Intest Res 2023; 21:43-60. [PMID: 36245343 PMCID: PMC9911268 DOI: 10.5217/ir.2022.00029] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/21/2022] [Accepted: 04/18/2022] [Indexed: 11/05/2022] Open
Abstract
Crohn's disease (CD) is a relapsing and progressive condition characterized by diarrhea, abdominal pain, weight loss, and hematochezia that results in serious complications such as perforations, fistulas, and abscesses. Various medications, interventions, and surgical treatments have been used to treat CD. The Korean guidelines for CD management were distributed in 2012 and revised in 2017 by the Inflammatory Bowel Disease (IBD) Research Group of the Korean Association for the Study of Intestinal Diseases. Substantial progress in mucosal immunologic research has elucidated the pathophysiology of IBD, leading to development of biological agents for treatment of CD. The first developed biologic agent, tumor necrosis factor-α agents, were shown to be efficacious in CD, heralding a new era in management of CD. Subsequently, vedolizumab, a monoclonal antibody against integrin α4β7, and ustekinumab, a human monoclonal antibody that inhibits the common p40 subunit of interleukin-12 and interleukin-23, were both approved for clinical use and are efficacious and safe for both induction and maintenance of remission in moderate-to-severe CD patients. Moreover, a recent study showed the non-inferiority of CT-P13, an infliximab biosimilar, compared with infliximab in CD patients. The third Korean guidelines for CD management provide updated information regarding treatment of moderate-to-severe CD patients with biologic agents.
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Affiliation(s)
- Seong-Joon Koh
- Department of Internal Medicine, Liver Research Institute and Seoul National University College of Medicine, Seoul, Korea
| | - Sung Noh Hong
- Department of Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Soo-Kyung Park
- Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Byong Duk Ye
- Department of Gastroenterology and Inflammatory Bowel Disease Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Kyeong Ok Kim
- Department of Internal Medicine, Yeungnam University College of Medicine, Daegu, Korea
| | - Jeong Eun Shin
- Department of Internal Medicine, Dankook University College of Medicine, Cheonan, Korea
| | - Yong Sik Yoon
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Hong Sub Lee
- Department of Internal Medicine, Inje University College of Medicine, Busan, Korea
| | - Sung Hoon Jung
- Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Miyoung Choi
- National Evidence-based Healthcare Collaborating Agency (NECA), Seoul, Korea
| | - Soo-Young Na
- Department of Internal Medicine, Incheon St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Incheon, Korea
| | - Chang Hwan Choi
- Department of Internal Medicine, Chung-Ang University College of Medicine, Seoul, Korea
| | - Joo Sung Kim
- Department of Internal Medicine, Liver Research Institute and Seoul National University College of Medicine, Seoul, Korea,Correspondence to Joo Sung Kim, Department of Internal Medicine, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul 03080, Korea. Tel: +82-2-740-8112, Fax: +82-2-743-6701, E-mail:
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50
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Rintala RJ, Pakarinen MP. Inflammatory Bowel Disease. PEDIATRIC SURGERY 2023:1031-1050. [DOI: 10.1007/978-3-030-81488-5_76] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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