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Na JE, Jung SH, Choi A, Kim S, Kim TO. Nationwide study on clinical impact of early tumor necrosis factor-α inhibitors following first intestinal resection in biologics-naïve Crohn's disease patients. Sci Rep 2025; 15:12532. [PMID: 40216839 PMCID: PMC11992071 DOI: 10.1038/s41598-025-88364-y] [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: 05/31/2024] [Accepted: 01/28/2025] [Indexed: 04/14/2025] Open
Abstract
In Crohn's disease (CD) patients who have undergone surgery, postoperative recurrence remains a challenge, and there is a lack of investigation into the impact of early anti-tumor necrosis factor (TNF) therapy following surgery on clinical outcomes compared to late use of anti-TNF agents. Utilizing the Health Insurance Review and Assessment database, we conducted a retrospective cohort study comprising 481 CD patients who underwent their first intestinal resection and were naïve to preoperative biological therapy from 2010 to 2018. Patients initiating anti-TNF agents early (within one year post-surgery) were compared to those starting later for prognosis. Clinical outcomes, including biologics switching and surgical recurrence, were assessed. The late start group (n = 290) exhibited a higher surgical recurrence rate (27.9% vs. 18.3%, p-value = 0.021), while biologics switching rates did not significantly differ (8.3% vs. 12.6%, p-value = 0.167) compared to the early start group (n = 191). Kaplan-Meier curves revealed no significant differences in the risk of biologics switching (p-value = 0.319) or surgical recurrence (p-value = 0.380) between the early and late start groups. This study investigated the potential role of early anti-TNF therapy after first intestinal resection in biologics-naïve CD patients compared to late initiation. Further refined prospective research is warranted to validate these comparisons.
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Affiliation(s)
- Ji Eun Na
- Division of Gastroenterology, Department of Internal Medicine, Haeundae Paik Hospital, Inje University College of Medicine, 875 Haeundae-ro, Haeundae-gu, Busan, 48108, Korea
| | - Sung Hoon Jung
- Division of Gastroenterology, Department of Internal Medicine, Eunpyeong St. Mary's Hospital, College of Medicine, The Catholic University of Korea, 1021, Tongil-ro, Eunpyeong-gu, Seoul, 03312, Republic of Korea.
| | - Arum Choi
- Department of Preventive Medicine and Public Health, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Sukil Kim
- Department of Preventive Medicine and Public Health, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Tae-Oh Kim
- Division of Gastroenterology, Department of Internal Medicine, Haeundae Paik Hospital, Inje University College of Medicine, 875 Haeundae-ro, Haeundae-gu, Busan, 48108, Korea.
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2
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Fansiwala K, Spartz EJ, Roney AR, Kwaan MR, Sauk JS, Chen PH, Limketkai BN. Increasing Rates of Bowel Resection Surgery for Stricturing Crohn's Disease in the Biologic Era. Inflamm Bowel Dis 2025; 31:935-943. [PMID: 38795051 PMCID: PMC11985397 DOI: 10.1093/ibd/izae113] [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: 02/08/2024] [Indexed: 05/27/2024]
Abstract
BACKGROUND The era of biologics is associated with declining rates of surgery for Crohn's disease (CD), but the impact on surgery for stricturing CD is unknown. Our study aimed to assess nationwide trends in bowel resection surgery for obstruction in CD since the introduction of infliximab for CD in 1998. METHODS Using the Nationwide Inpatient Sample, we performed a nationwide analysis, identifying patients hospitalized for CD who underwent bowel resection for an indication of obstruction between 1998 and 2020 (era of biologics). Longitudinal trends in all CD-related resections and resection for obstruction were evaluated. Multivariable logistic regression identified patient and hospital characteristics associated with bowel resection surgery for obstruction. RESULTS Hospitalizations for all CD-related resections decreased from 12.0% of all hospitalizations in 1998 to 6.9% in 2020, while hospitalizations for CD-related resection for obstructive indication increased from 1.3% to 2.0%. The proportion of resections for obstructive indication amongst all CD-related bowel resections increased from 10.8% in 1998 to 29.1% in 2020. In the multivariable models stratified by elective admission, the increasing year was associated with risk of resection for obstructive indication regardless of urgency (nonelective model: odds ratio, 1.01; 95% CI, 1.00-1.02; elective model: odds ratio, 1.06; 95% CI, 1.04-1.08). CONCLUSIONS In the era of biologics, our findings demonstrate a decreasing annual rate of CD-related bowel resections but an increase in resection for obstructive indication. Our findings highlight the effect of medical therapy on surgical rates overall but suggest limited impact of current medical therapy on need of resection for stricturing disease.
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Affiliation(s)
- Kush Fansiwala
- Vatche and Tamar Manoukian Division of Digestive Diseases, Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA
| | - Ellen J Spartz
- Department of Surgery, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA
| | - Andrew R Roney
- Vatche and Tamar Manoukian Division of Digestive Diseases, Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA
| | - Mary R Kwaan
- Department of Surgery, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA
| | - Jenny S Sauk
- Vatche and Tamar Manoukian Division of Digestive Diseases, Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA
| | - Po-Hung Chen
- Division of Gastroenterology and Hepatology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Berkeley N Limketkai
- Vatche and Tamar Manoukian Division of Digestive Diseases, Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA
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3
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Newton C, Fichera A. Anastomosis after Bowel Resection for Crohn's Disease: State of the Art Review. Clin Colon Rectal Surg 2025; 38:104-112. [PMID: 39944304 PMCID: PMC11813605 DOI: 10.1055/s-0044-1786534] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/04/2025]
Abstract
Recurrence after surgically induced remission in Crohn's disease remains a topic of research and debate with significant clinical implications for overall quality of life and intestinal and defecatory functions. While the surgeon continues to play a critical role in surgical prophylaxis of recurrence, optimal results will only be obtained in the setting of a true multidisciplinary team approach, following the principles of "the right surgery, on the right patient, at the right time, performed by the right surgeon, supported by the right team." The centerpiece of surgical prophylaxis is the intestinal anastomosis. The ideal anastomosis after resection for Crohn's disease should be safe and reliable, as postoperative septic complications have been shown to increase the risk of recurrence; result in a wide lumen and a configuration that would not impede enteric flow; exclude or excise the mesentery, a known culprit in primary and recurrent disease; and preserve vascularization and innervation. This article will review the evidence supporting the above-mentioned surgical principles and the long-term results of the different anastomotic configurations.
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Affiliation(s)
- Carla Newton
- Division of Colon and Rectal Surgery, Department of Surgery, Baylor Scott & White Medical Center, Baylor College of Medicine, Temple, Texas
| | - Alessandro Fichera
- Division of Colon and Rectal Surgery, Baylor University Medical Center, Texas A&M University, Dallas, Texas
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4
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Bouwknegt DG, van der Weide AHC, Dijkstra G, Goetgebuer RL, Oldenburg L, van Dop WA, Hirdes MMC, Prins JR, Hoogenboom FJ, van der Woude CJ, Visschedijk MC. Pregnancy With a Stoma is Feasible, Though Associated With Manageable Complications. Inflamm Bowel Dis 2025:izae301. [PMID: 39756433 DOI: 10.1093/ibd/izae301] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/19/2024] [Indexed: 01/07/2025]
Abstract
BACKGROUND Inflammatory bowel disease (IBD) is often diagnosed in young adults, and therefore frequently coincides with pregnancy. Patients may require surgery that includes (temporary) stoma placement. Literature on the occurrence of stoma-complications during pregnancy and the effect on pregnancy outcomes is limited. To evaluate stoma- complications peri- and postpartum, a retrospective study was performed in women who were pregnant while having a stoma. METHODS This multicentre cohort and survey study included all pregnant patients with IBD and a stoma who delivered between 2016 and 2023 from 5 Dutch university hospitals. Stoma-complications and pregnancy outcomes were retrospectively collected from electronic patient files. A questionnaire assessed patient-reported complications and long-term stoma-related complaints. RESULTS In total, 50 patients were included (median age at conception 31.0 years; 55.2% Crohn's disease and 44.8% ulcerative colitis), comprising 67 pregnancies, 5 of which ended in pregnancy loss. Stoma complications occurred in 44 full-term pregnancies (71.0%), most commonly obstruction (35.5%) and decreased output (29.0%). Surgery was required in four pregnancies due to obstruction (n = 3) and prolapse (n = 2). In the first-year postpartum, 7 patients required surgery for stoma-complications. Amongst 29 women who completed the questionnaire, 10 (34.5%) reported unresolved complications 6 months postpartum. Cesarean sections were performed in 31 (50.0%) pregnancies. Adverse pregnancy outcomes included prematurity (n = 9, 14.5%), low birth weight (n = 9, 14.5%), and dysmaturity (n = 5, 8.1%). CONCLUSIONS Pregnancy with a stoma is feasible, though manageable complications often occur. Counseling before pregnancy and close monitoring of symptoms during pregnancy and postpartum are essential for women with IBD and a stoma.
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Affiliation(s)
- Dianne Gelien Bouwknegt
- Department of Gastroenterology and Hepatology, University Medical Center Groningen, University of Groningen, 9713GZ, Groningen, The Netherlands
| | | | - Gerard Dijkstra
- Department of Gastroenterology and Hepatology, University Medical Center Groningen, University of Groningen, 9713GZ, Groningen, The Netherlands
| | - Rogier Leon Goetgebuer
- Department of Gastroenterology and Hepatology, Amsterdam University Medical Center, 1105AZ, Amsterdam, The Netherlands
| | - Lotte Oldenburg
- Department of Gastroenterology and Hepatology, Amsterdam University Medical Center, 1105AZ, Amsterdam, The Netherlands
| | - Willemijn Alexandra van Dop
- Department of Gastroenterology and Hepatology, Radboud University Medical Center, 6525GA, Nijmegen, The Netherlands
| | | | - Jelmer Riemer Prins
- Department of Obstetrics and Gynaecology, University Medical Center Groningen, University of Groningen, 9713GZ, Groningen, The Netherlands
| | - Froukje Jantien Hoogenboom
- Department of Colorectal Surgery, University Medical Center Groningen, University of Groningen, 9713GZ, Groningen, The Netherlands
| | | | - Marijn Caroline Visschedijk
- Department of Gastroenterology and Hepatology, University Medical Center Groningen, University of Groningen, 9713GZ, Groningen, The Netherlands
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Nasasra A, Morrison TEM, Luberto A, Carvello M, Williams KJ, Davies J, Spinelli A, Mehta AM, Warusavitarne JH. Recurrence rates after strictureplasty for small bowel Crohn's disease remain high in the era of biologics. Colorectal Dis 2024. [PMID: 39515997 DOI: 10.1111/codi.17224] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/20/2024] [Revised: 07/28/2024] [Accepted: 09/11/2024] [Indexed: 11/16/2024]
Abstract
AIM Despite advancements in therapeutic options for Crohn's disease (CD), strictureplasty is a mainstay bowel-preserving technique for small bowel CD. We sought to audit international practice across three high-volume centres since the widespread use of biologic medication. METHODS A retrospective audit was performed for all strictureplasties undertaken for small bowel CD, over a 15-year period (2006-2021), in three high-volume centres in the United Kingdom and Italy. Primary endpoints were clinical recurrence and reoperation for recurrence. RESULTS In all, 123 patients were included; 58% were men, 25% smoked and 60% had previous abdominal surgery for CD. Median age was 40 years (interquartile range 30-52 years), mean body mass index 22 (15-31) and median disease duration 138 months (81-255 months). 42% had been treated with biologics preoperatively. In total 338 strictureplasties were performed in 123 patients, with a median of two per patient (interquartile range 1-3). Complications occurred in 35%, with 8% scoring Clavien-Dindo Grade 3. There were no Grade 4/5 complications. Postoperative biologic treatment was administered to 84/123 patients (68.3%). Median follow-up was 54 months. 41/123 patients (33.3%) developed clinical recurrence. Reoperation for recurrent stricturing was performed in 26/123 patients (21%). Clinical recurrence and reoperation rates were significantly higher in patients who continued to smoke after their index surgery. CONCLUSION Strictureplasty remains a safe and effective surgical treatment for small bowel CD. Recurrence and reoperation rates remain high, regardless of postoperative biologic therapy. Smoking significantly increases the risk of recurrence.
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Affiliation(s)
- A Nasasra
- Department of Colorectal Surgery, St Mark's Hospital, London North West University Hospitals NHS Trust, London, UK
| | - T E M Morrison
- Cambridge Colorectal Unit, Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
| | - A Luberto
- Division of Colon and Rectal Surgery, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy
| | - M Carvello
- Division of Colon and Rectal Surgery, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy
| | - K J Williams
- Department of Colorectal Surgery, Frimley Health NHS Foundation Trust, Frimley, UK
| | - J Davies
- Cambridge Colorectal Unit, Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
- University of Cambridge, Cambridge, UK
| | - A Spinelli
- Division of Colon and Rectal Surgery, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy
| | - A M Mehta
- Department of Colorectal Surgery, St Mark's Hospital, London North West University Hospitals NHS Trust, London, UK
| | - J H Warusavitarne
- Department of Colorectal Surgery, St Mark's Hospital, London North West University Hospitals NHS Trust, London, UK
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Silva ACV, Tumelero TJ, Yamamoto DR, Truppel SK, da Silva GS, Ribeiro LBM, Zacharias P, Olandoski M, Magro DO, Vieira MC, Kotze PG. Biological therapy, surgery, and hospitalization rates for inflammatory bowel disease: An observational Latin American comparative study between adults and pediatric patients. GASTROENTEROLOGIA Y HEPATOLOGIA 2024; 47:813-820. [PMID: 37890582 DOI: 10.1016/j.gastrohep.2023.10.006] [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: 08/23/2023] [Revised: 10/07/2023] [Accepted: 10/09/2023] [Indexed: 10/29/2023]
Abstract
OBJECTIVE Compare the proportions of use of biological therapy, surgeries, and hospitalizations between adults and pediatric inflammatory bowel disease (IBD)-Crohn's disease (CD) and ulcerative colitis (UC)-patients. PATIENTS AND METHODS Observational, retrospective, and multicenter study. Data were collected from all consecutive IBD patients seen as outpatients or admitted to hospital, during 2015-2021, in two IBD tertiary centers in a South Brazilian capital. Patients with unclassified colitis diagnosis were excluded from this study. Patients were classified as having CD or UC and sub-categorized as adult or pediatric according to age. Data were analyzed using frequency, proportion, Fisher's exact test, and Chi-square test. RESULTS A total of 829 patients were included: 509 with CD (378 adults/131 pediatric) and 320 with UC (225/95). Among patients with CD, no differences were observed for proportions of use of biological therapy (80.2% in pediatric vs. 73.3% in adults; P=0.129), surgery (46.6% vs. 50.8%; P=0.419), or hospitalization (64.9% vs. 56.9%; P=0.122). In UC, significant differences were observed for biological therapy (40.0% vs. 28.0%; P=0.048) and hospitalization (47.4% vs. 24.0%; P<0.001). No significant difference was observed in surgery rates (17.9% vs. 12.4%; P=0.219). CONCLUSIONS Biological therapy and incidence of hospitalization were greater among pediatric patients with UC, compared with adults; no difference was observed in the need for abdominal surgery. In CD, no significant difference was observed in the three main outcomes between the age groups.
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Affiliation(s)
| | - Tainá Júlia Tumelero
- Health Sciences Postgraduate Program, Pontifícia Universidade Católica do Paraná (PUCPR), Curitiba, Brazil
| | | | | | | | | | - Patricia Zacharias
- Health Sciences Postgraduate Program, Pontifícia Universidade Católica do Paraná (PUCPR), Curitiba, Brazil
| | - Marcia Olandoski
- Biostatistics, Pontifícia Universidade Católica do Paraná (PUCPR), Curitiba, Brazil
| | | | - Mário César Vieira
- Pediatric Gastroenterology Unit, Pequeno Príncipe Hospital, Curitiba, Brazil
| | - Paulo Gustavo Kotze
- Health Sciences Postgraduate Program, Pontifícia Universidade Católica do Paraná (PUCPR), Curitiba, Brazil
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7
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Sun Z, Cao L, Chen Y, Zhu W, Li Y. Long-term outcomes of intestinal penetrating Crohn's disease following successful nonoperative management. Eur J Gastroenterol Hepatol 2024; 36:867-874. [PMID: 38625818 DOI: 10.1097/meg.0000000000002775] [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: 04/18/2024]
Abstract
There is a paucity of data on the surgical or medical treatment for abscess/fistula complicating Crohn's disease after successful nonsurgical management. We conducted a cohort study to investigate the long-term outcomes and the risk factors for the requirement of subsequent surgical intervention in Crohn's disease patients with complicating fistulas/abscess following successful nonsurgical management. Data were collected on penetrating Crohn's disease experiencing successful nonsurgical treatment between December 2012 and December 2021. Long-term outcomes and risk factors of surgery were assessed by univariate and multivariate analysis, and subgroup analysis was performed based on penetrating phenotype including abscess, fistula, and phlegmon. A total of 523 penetrating Crohn's disease patients; there were 390, 125, and 60 patients complicated with fistulas, abscess, and phlegmon, respectively. Long-term outcomes showed that BMI < 18.5 (kg/m 2 ), the recurrent abscess, and stricture were independent risk factors of surgery. Biologics and resolution of abscess were independent protective factors of surgery. Furthermore, in 399 patients undergoing early surgery, stricture and BMI < 18.5 (kg/m 2 ) were independent risk factors, and biologics and abscess resolution were protective of the early surgery. Subgroup analysis based on fistula, abscess, and phlegmon phenotype also demonstrated that concomitant stricture was an independent risk factor and the use of biologics was protective of surgical resection. Our data indicate that biologics can delay the requirement of surgery and may be given to patients with penetrating complicating Crohn's disease who have been successfully treated nonoperatively, but surgical resection should be considered in the setting of malnutrition and stenosis formation.
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Affiliation(s)
- Zhenya Sun
- Department of General Surgery, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University
| | - Lei Cao
- Department of General Surgery, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University
| | - Yusheng Chen
- Department of General Surgery, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University
| | - Weiming Zhu
- Department of Anorectal Surgery, IBD Therapeutic Center, Nanjing University of Chinese Medicine, Nanjing, PR China
| | - Yi Li
- Department of General Surgery, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University
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8
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Sinclair J, Brooks-Warburton J, Bottoms L. Perceptions, behaviours and barriers towards exercise practices in inflammatory bowel disease. PLoS One 2024; 19:e0299228. [PMID: 38578737 PMCID: PMC10997097 DOI: 10.1371/journal.pone.0299228] [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: 10/11/2023] [Accepted: 02/04/2024] [Indexed: 04/07/2024] Open
Abstract
Inflammatory bowel disease (IBD), a chronic disease affecting the digestive tract, has a significant impact on health-related quality of life. Pharmaceutical treatment is typically adopted, yet exercise is increasingly becoming recognized as an adjunct therapy. This study aimed to explore the perspectives, behaviours, and barriers of IBD patients in terms of their exercise habits. A 16-item closed-ended questionnaire was completed by 463 adult IBD patients (Ulcerative colitis = 57.02%, Crohn's dis-ease = 40.60% and Other = 2.38%) (Female = 76.67%, Male = 22.46 and Non-binary = 0.86%). The questionnaire was divided into three sections: baseline/demographic characteristics, disease characteristics, and exercise perceptions, beliefs, and behaviours. Significantly (P<0.001) more participants (63.07%) reported that they engage regularly with exercise compared to those who do not; however, engagement was significantly lower in female patients (59.72%) compared to males (74.04%). Respondents also rated significantly (P<0.001) that a combination of factors prevents engagement in exercise (74.30%). Moderate intensity exercise was the predominant (P<0.001) aerobic modality (39.04%), the majority (P<0.001) response was that patients undertake no resistance training (27.74%), and significantly more (P<0.001) patients indicated that they don't know whether resistance training can influence IBD either positively (57.53%) or negatively (62.33%). Whilst it is encouraging that IBD patients are engaging regularly with exercise, the reduced levels of engagement in females and lack of knowledge/ engagement with resistance training, indicate that future implementation and educational developments are necessary to enhance exercise in females and resistance training engagement in all IBD patients.
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Affiliation(s)
- Jonathan Sinclair
- Research Centre for Applied Sport, Physical Activity and Performance, School of Sport & Health Sciences, Faculty of Allied Health and Wellbeing, University of Central Lancashire, Lancashire, United Kingdom
| | | | - Lindsay Bottoms
- Centre for Research in Psychology and Sport Sciences, School of Life and Medical Sciences, University of Hertfordshire, Hertfordshire, United Kingdom
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Ng AP, Chervu N, Porter G, Mallick S, Le N, Benharash P, Lee H. Cost variation of nonelective surgery for ulcerative colitis across the United States. J Gastrointest Surg 2024; 28:488-493. [PMID: 38583900 DOI: 10.1016/j.gassur.2024.01.036] [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: 12/13/2023] [Revised: 01/07/2024] [Accepted: 01/27/2024] [Indexed: 04/09/2024]
Abstract
BACKGROUND Although clinical outcomes of surgery for ulcerative colitis (UC) have improved in the modern biologic era, expenditures continue to increase. A contemporary cost analysis of UC operative care is lacking. The present study aimed to characterize risk factors and center-level variation in hospitalization costs after nonelective resection for UC. METHODS All adults with UC in the 2016-2020 Nationwide Readmissions Database undergoing nonelective colectomy or rectal resection were identified. Mixed-effects models were developed to evaluate patient and hospital factors associated with costs. Random effects were estimated and used to rank hospitals by increasing risk-adjusted center-level costs. High-cost hospitals (HCHs) in the top decile of expenditure were identified, and their association with select outcomes was subsequently assessed. RESULTS An estimated 10,280 patients met study criteria with median index hospitalization costs of $40,300 (IQR, $26,400-$65,000). Increased time to surgery was significantly associated with a +$2500 increment in costs per day. Compared with low-volume hospitals, medium- and high-volume centers demonstrated a -$5900 and -$8200 reduction in costs, respectively. Approximately 19.2% of variability in costs was attributable to interhospital differences rather than patient factors. Although mortality and readmission rates were similar, HCH status was significantly associated with increased complications (adjusted odds ratio [AOR], 1.39), length of stay (+10.1 days), and nonhome discharge (AOR, 1.78). CONCLUSION The present work identified significant hospital-level variation in the costs of nonelective operations for UC. Further efforts to optimize time to surgery and regionalize care to higher-volume centers may improve the value of UC surgical care in the United States.
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Affiliation(s)
- Ayesha P Ng
- Cardiovascular Outcomes Research Laboratories, David Geffen School of Medicine at UCLA, Los Angeles, California, United States
| | - Nikhil Chervu
- Cardiovascular Outcomes Research Laboratories, David Geffen School of Medicine at UCLA, Los Angeles, California, United States
| | - Giselle Porter
- Cardiovascular Outcomes Research Laboratories, David Geffen School of Medicine at UCLA, Los Angeles, California, United States
| | - Saad Mallick
- Cardiovascular Outcomes Research Laboratories, David Geffen School of Medicine at UCLA, Los Angeles, California, United States
| | - Nguyen Le
- Cardiovascular Outcomes Research Laboratories, David Geffen School of Medicine at UCLA, Los Angeles, California, United States
| | - Peyman Benharash
- Cardiovascular Outcomes Research Laboratories, David Geffen School of Medicine at UCLA, Los Angeles, California, United States; Division of Cardiac Surgery, Department of Surgery, David Geffen School of Medicine at UCLA, Los Angeles, California, United States
| | - Hanjoo Lee
- Division of Colon and Rectal Surgery, Department of Surgery, Harbor-UCLA Medical Center, Torrance, California, United States.
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10
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Fanizza J, D'Amico F, Lauri G, Martinez-Dominguez SJ, Allocca M, Furfaro F, Zilli A, Fiorino G, Parigi TL, Radice S, Peyrin-Biroulet L, Danese S. The role of filgotinib in ulcerative colitis and Crohn's disease. Immunotherapy 2024; 16:59-74. [PMID: 38009327 DOI: 10.2217/imt-2023-0116] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2023] [Accepted: 10/09/2023] [Indexed: 11/28/2023] Open
Abstract
Filgotinib is an oral small molecule that selectively inhibits JAK1. It is already approved for the treatment of moderately to severely active ulcerative colitis (UC). Ongoing studies are evaluating the efficacy and safety of filgotinib in Crohn's disease (CD). The purpose of this review is to summarize the available data regarding filgotinib in the management of UC and CD. We used Pubmed, Embase and clinicaltrials.gov websites to search all available data and currently ongoing studies regarding the efficacy and safety of filgotinib in inflammatory bowel diseases. Filgotinib is an effective and safe drug for the management of biologic-naive and biologic-experienced patients with moderate-to-severe UC. The same efficacy results have not been achieved in CD.
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Affiliation(s)
- Jacopo Fanizza
- Department of Gastroenterology & Endoscopy, IRCCS San Raffaele Hospital & Vita-Salute San Raffaele University, Milan, Italy
| | - Ferdinando D'Amico
- Department of Gastroenterology & Endoscopy, IRCCS San Raffaele Hospital & Vita-Salute San Raffaele University, Milan, Italy
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy
| | - Gaetano Lauri
- Department of Gastroenterology & Endoscopy, IRCCS San Raffaele Hospital & Vita-Salute San Raffaele University, Milan, Italy
| | - Samuel J Martinez-Dominguez
- Department of Gastroenterology, Hospital Clínico Universitario Lozano Blesa, Zaragoza, Spain; Aragón Health Research Institute, Zaragoza, Spain; School of Medicine, University of Zaragoza, Spain
| | - Mariangela Allocca
- Department of Gastroenterology & Endoscopy, IRCCS San Raffaele Hospital & Vita-Salute San Raffaele University, Milan, Italy
| | - Federica Furfaro
- Department of Gastroenterology & Endoscopy, IRCCS San Raffaele Hospital & Vita-Salute San Raffaele University, Milan, Italy
| | - Alessandra Zilli
- Department of Gastroenterology & Endoscopy, IRCCS San Raffaele Hospital & Vita-Salute San Raffaele University, Milan, Italy
| | - Gionata Fiorino
- Department of Gastroenterology & Endoscopy, IRCCS San Raffaele Hospital & Vita-Salute San Raffaele University, Milan, Italy
| | - Tommaso Lorenzo Parigi
- Department of Gastroenterology & Endoscopy, IRCCS San Raffaele Hospital & Vita-Salute San Raffaele University, Milan, Italy
| | - Simona Radice
- Department of Gastroenterology & Endoscopy, IRCCS San Raffaele Hospital & Vita-Salute San Raffaele University, Milan, Italy
| | - Laurent Peyrin-Biroulet
- University of Lorraine, Inserm, NGERE, F-54000 Nancy, France
- Department of Gastroenterology, Nancy University Hospital, F-54500 Vandœuvre-lès-Nancy, France
| | - Silvio Danese
- Department of Gastroenterology & Endoscopy, IRCCS San Raffaele Hospital & Vita-Salute San Raffaele University, Milan, Italy
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Yoshida S, Imai S, Fushimi K. Changes in surgery rates among hospitalized patients with inflammatory bowel disease in Japan from 2015 to 2019: A nationwide administrative database analysis. J Gastroenterol Hepatol 2024; 39:272-279. [PMID: 37961024 DOI: 10.1111/jgh.16387] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/11/2023] [Revised: 09/17/2023] [Accepted: 10/10/2023] [Indexed: 11/15/2023]
Abstract
BACKGROUND AND AIM Treatment of inflammatory bowel disease (IBD), consisting of ulcerative colitis (UC) and Crohn's disease (CD), has advanced with the application of biologics or Janus kinase inhibitor (JAKi); however, some patients still need surgery. We assessed time trends of surgery and biologics or JAKi variety in Japan. METHODS Patients hospitalized due to IBD were analyzed using Diagnosis Procedure Combination data between 2015 and 2019. Longitudinal trend analysis was performed for demographics, and interrupted time-series analysis was performed to examine the association between surgery rates and an increase in the types of biologics or JAKi. RESULTS Totally, 37 867 cases with UC and 35 493 cases with CD were analyzed. Over 5 years, the surgery rate decreased in both UC and CD. The proportion of biologics and JAKi usage increased in UC and stabilized in CD. Between decreasing surgery and expanding treatment options of biologic or JAKi, interrupted time-series analysis results showed no significant correlation (level change in UC, -1.13, 95% confidence interval [CI]: -2.11 to -0.16, P = 0.0235; slope change in UC, -0.05, 95% CI: -0.26 to 0.16, P = 0.6372; level change in CD, -0.55, 95% CI: -1.82 to 0.71, P = 0.3815; slope change in CD, -0.22, 95% CI: -0.63 to 0.19, P = 0.2892). CONCLUSIONS In Japan, from 2015 to 2019, the use of biologics or JAKi increased for UC and slightly decreased for CD, while the number of surgeries decreased in both. Our findings suggest that more widespread use of biologics or JAKi therapy could reduce surgeries in patients with IBD.
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Affiliation(s)
- Shoko Yoshida
- Department of Health Policy and Informatics, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan
- Inflammation and Immunology Medical Affairs, Pfizer Japan Inc, Tokyo, Japan
| | - Shinobu Imai
- Department of Health Policy and Informatics, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan
- Department of Healthcare and Regulatory Sciences, Division of Pharmacoepidemiology, Showa University School of Pharmacy, Tokyo, Japan
| | - Kiyohide Fushimi
- Department of Health Policy and Informatics, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan
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12
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Jin R, Kruppert S, Scholz F, Bardoulat I, Karzazi K, Kricorian G, O’Kelly JL, Reinisch W. Treatment persistence and switching patterns of ABP 501 in European patients with inflammatory bowel disease. Therap Adv Gastroenterol 2024; 17:17562848231222332. [PMID: 38221908 PMCID: PMC10787526 DOI: 10.1177/17562848231222332] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/31/2023] [Accepted: 12/06/2023] [Indexed: 01/16/2024] Open
Abstract
Background Approval of the adalimumab (ADA) biosimilar ABP 501 for inflammatory bowel disease (IBD) indications was based on the principle of extrapolation, without indication-specific clinical trial data. Objectives To evaluate the real-world treatment patterns of ABP 501 in patients with IBD. Design Retrospective analysis of pharmacy claims data from Germany and France. Methods Continuously insured adult IBD patients who initiated ABP 501 between October 2018 and March 2020 were included. Treatment persistence, adherence, and post-ABP 501 switching patterns were evaluated for two mutually exclusive groups: ADA-naïve patients (i.e. no baseline use of ADA products) and ADA-experienced patients (i.e. previously treated with ADA products). Results A total of 3362 German patients and 733 French patients were included, with 54.4% and 65.3% being ADA-naïve patients, respectively. Median persistence (95% CI) on ABP 501 was 10.9 months (9.8-11.6) in ADA-naïve patients and 14.2 months (12.7-15.2) in ADA-experienced patients in Germany; for the French cohort, ADA-naïve and -experienced patients had median persistence of 12.8 months (10.2-14.7) and 11.5 months (8.8-14.4), respectively. During the first 12 months of ABP 501 initiation, 53.7% of German patients and 51.0% of French patients were adherent to the therapy. About 20% of patients in both countries switched from ABP 501 to another targeted therapy. In the German cohort, ADA-naïve patients most frequently switched to non-tumor necrosis factor inhibitor biologics, but ADA-experienced patients most commonly switched to reference product (RP); in the French cohort, patients most often switched to RP regardless of prior exposure to ADA products. Conclusion About 50% of patients persisted on and were adherent to ABP 501 therapy during the first 12 months after treatment initiation in two large European countries. Post-ABP 501, switching patterns varied between countries, indicating diversified treatment practices warranting further research on reason(s) for switching and potential overall treatment outcomes.
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Affiliation(s)
- Ran Jin
- Amgen Inc., 1 Amgen Center Dr, Thousand Oaks, CA 91320, USA
| | | | | | | | | | | | | | - Walter Reinisch
- Division of Gastroenterology and Hepatology, Medical University of Vienna, Vienna, Austria
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13
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Maev IV, Bakulin IG, Skalinskaya MI, Skazyvaeva EV. [Inflammatory bowel diseases: Transformation of representations. A review]. TERAPEVT ARKH 2023; 95:1064-1074. [PMID: 38158940 DOI: 10.26442/00403660.2023.12.202507] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/26/2023] [Indexed: 01/03/2024]
Abstract
The global burden of inflammatory bowel disease (IBD) is currently significant and continues to grow due to the increasing prevalence of ulcerative colitis (UC) and Crohn's disease (CD), the increasing costs of diagnosis and treatment, and the high level of disability in patients with this disease. Categories, which leads to the search for risk factors and predictors of aggressive course and extraintestinal manifestations. According to the latest data, the prevalence of UC in Russia is 16.6 per 100 000 population, the annual registered increase is 11.3%; the prevalence of CD is 5.6 per 100 000 population, and the increase is 13.7%. In the Russian population of patients with IBD, the average age of disease onset is 35.3 years for UC and 31.2 years for CD. Moreover, in 89.3% of patients with UC, it took at least 2 years to verify the diagnosis, and in CD, within 2 years from the onset of clinical symptoms, the diagnosis was established in only 72.6% of patients. One of the dominant characteristics of IBD is its multisystem nature, which leads to the development of extraintestinal manifestations (ECM), which can be observed in 50-60% of patients, while up to 25% of patients with IBD have several EMC and the most common variants are joint lesions. A higher frequency of extraintestinal manifestations is observed in CD (up to 45% of patients), in female patients, in smokers and with a longer duration of the disease. To predict clinical remission, the level of fecal calprotectin and CRP, the need for glucocorticosteroids are important, to predict endoscopic remission - the level of fecal calprotectin, and to predict histological remission, an endoscopic Schroeder index value of ≤1 is important. The absolute risk of developing colorectal cancer in IBD remains relatively low, ranging from 1.1 to 5.4% after 20 years of disease. The main risk factors for IBD are total intestinal damage, high inflammatory activity, the stricturing phenotype of CD and the presence of primary sclerosing cholangitis.
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Affiliation(s)
- I V Maev
- Yevdokimov Moscow State University of Medicine and Dentistry
| | - I G Bakulin
- Mechnikov North-Western State Medical University
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14
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Ananthakrishnan AN, Adler J, Chachu KA, Nguyen NH, Siddique SM, Weiss JM, Sultan S, Velayos FS, Cohen BL, Singh S. AGA Clinical Practice Guideline on the Role of Biomarkers for the Management of Crohn's Disease. Gastroenterology 2023; 165:1367-1399. [PMID: 37981354 DOI: 10.1053/j.gastro.2023.09.029] [Citation(s) in RCA: 18] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/21/2023]
Abstract
BACKGROUND & AIMS Biomarkers are used frequently for evaluation and monitoring of patients with Crohn's disease (CD). This American Gastroenterological Association (AGA) guideline is intended to support practitioners in decisions about the use of biomarkers for the management of CD. METHODS A multidisciplinary panel of content experts and guideline methodologists used the Grading of Recommendations Assessment, Development and Evaluation framework to formulate patient-centered clinical questions and review evidence on the performance of fecal calprotectin, serum C-reactive protein (CRP), and Endoscopic Healing Index in patients with established CD who were asymptomatic, had symptoms of varying severity, or were in surgically induced remission. Biomarker performance was assessed against the gold standard of endoscopic activity, defined as a Simple Endoscopic Score for Crohn's Disease ≥3. The panel used the Grading of Recommendations Assessment, Development and Evaluation Evidence-to-Decision framework to develop recommendations for use of biomarkers in various settings. Implementation considerations were formulated for each recommendation to inform clinical practice. RESULTS The guideline panel made 11 conditional recommendations. In patients with CD in symptomatic remission, the panel suggests use of a biomarker- and symptom-based monitoring strategy over symptoms alone. In patients in symptomatic remission, a fecal calprotectin <150 μg/g and normal CRP rules out active inflammation, avoiding endoscopic evaluation for assessment of disease activity. However, elevated biomarkers in this setting merit confirmation with endoscopy before treatment adjustment. In patients with CD with mild symptoms, neither normal nor elevated biomarkers alone are sufficiently accurate to determine endoscopic activity. In patients with CD with moderate to severe symptoms, elevated fecal calprotectin or serum CRP suggests endoscopic activity, precluding routine endoscopic assessment for disease activity. In patients with CD in surgically induced remission in low-risk patients on pharmacologic prophylaxis, a normal fecal calprotectin reliably rules out endoscopic recurrence. In other postoperative settings, the panel suggests endoscopic assessment for establishing postoperative recurrence. CONCLUSIONS In patients with CD, fecal calprotectin and serum CRP can inform disease management in both asymptomatic and symptomatic disease. Discordance between symptom assessment and biomarker value may merit endoscopic evaluation for confirmation of status of disease activity.
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Affiliation(s)
- Ashwin N Ananthakrishnan
- Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts
| | - Jeremy Adler
- Division of Pediatric Gastroenterology, C.S. Mott Children's Hospital, Michigan Medicine, University of Michigan, Ann Arbor, Michigan; Susan B. Meister Child Health Evaluation and Research Center, University of Michigan, Ann Arbor, Michigan
| | - Karen A Chachu
- Division of Gastroenterology, Department of Medicine, Duke University, Durham, North Carolina
| | - Nghia H Nguyen
- Division of Gastroenterology, Kaiser Permanente Medical Group, Riverside, California
| | - Shazia M Siddique
- Division of Gastroenterology, Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania; Center for Evidence-Based Practice, University of Pennsylvania Health System, Philadelphia, Pennsylvania
| | - Jennifer M Weiss
- Division of Gastroenterology and Hepatology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin
| | - Shahnaz Sultan
- Division of Gastroenterology, Hepatology, and Nutrition, University of Minnesota, Minneapolis, Minnesota, and Veterans Affairs Healthcare System, Minneapolis, Minnesota
| | - Fernando S Velayos
- Division of Gastroenterology, Kaiser Permanente Medical Group, San Francisco, California
| | - Benjamin L Cohen
- Division of Gastroenterology, Hepatology, and Nutrition, Digestive Disease Institute, Cleveland Clinic, Cleveland, Ohio
| | - Siddharth Singh
- Division of Gastroenterology and Hepatology, University of California San Diego, La Jolla, California; Division of Biomedical Informatics, Department of Medicine, University of California San Diego, La Jolla, California
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15
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Mak JWY, Ho AHY, Ng SC. IBD barriers across the continents - East Asia. Therap Adv Gastroenterol 2023; 16:17562848231212089. [PMID: 38026101 PMCID: PMC10666695 DOI: 10.1177/17562848231212089] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/24/2023] [Accepted: 10/18/2023] [Indexed: 12/01/2023] Open
Abstract
Inflammatory bowel diseases (IBDs) are chronic illnesses with significant morbidities and impact on patients' quality of life. There has been a rapid increase in the incidence of IBD in East Asia in recent decades. However, there is a huge unmet need in the diagnosis and management of IBD in this region. With the increasing awareness of IBD in East Asia and a persistently high rate of tuberculosis in this region, this poses a significant challenge in the diagnosis and management of IBD. In this review, we will explore the barriers to the diagnosis and management of IBD in the East Asia, hoping to provide an insight on how to improve the healthcare system in the management of this complex disease.
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Affiliation(s)
- Joyce Wing Yan Mak
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Shatin, Hong Kong
| | - Agnes Hiu Yan Ho
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Shatin, Hong Kong
| | - Siew Chien Ng
- Department of Medicine and Therapeutics, Microbiota I-Center (MagIC), Center for Gut Microbiota Research, The Chinese University of Hong Kong, Shatin, Hong Kong
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16
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Long XQ, Liu MZ, Liu ZH, Xia LZ, Lu SP, Xu XP, Wu MH. Bile acids and their receptors: Potential therapeutic targets in inflammatory bowel disease. World J Gastroenterol 2023; 29:4252-4270. [PMID: 37545642 PMCID: PMC10401658 DOI: 10.3748/wjg.v29.i27.4252] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/08/2023] [Revised: 05/19/2023] [Accepted: 06/21/2023] [Indexed: 07/13/2023] Open
Abstract
Chronic and recurrent inflammatory disorders of the gastrointestinal tract caused by a complex interplay between genetics and intestinal dysbiosis are called inflammatory bowel disease. As a result of the interaction between the liver and the gut microbiota, bile acids are an atypical class of steroids produced in mammals and traditionally known for their function in food absorption. With the development of genomics and metabolomics, more and more data suggest that the pathophysiological mechanisms of inflammatory bowel disease are regulated by bile acids and their receptors. Bile acids operate as signalling molecules by activating a variety of bile acid receptors that impact intestinal flora, epithelial barrier function, and intestinal immunology. Inflammatory bowel disease can be treated in new ways by using these potential molecules. This paper mainly discusses the increasing function of bile acids and their receptors in inflammatory bowel disease and their prospective therapeutic applications. In addition, we explore bile acid metabolism and the interaction of bile acids and the gut microbiota.
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Affiliation(s)
- Xiong-Quan Long
- Department of Gastroenterology, The First Affiliated Hospital of Hunan Normal University (Hunan Provincial People's Hospital), Changsha 410005, Hunan Province, China
| | - Ming-Zhu Liu
- Department of Gastroenterology, The First Affiliated Hospital of Hunan Normal University (Hunan Provincial People's Hospital), Changsha 410005, Hunan Province, China
| | - Zi-Hao Liu
- Department of Gastroenterology, The First Affiliated Hospital of Hunan Normal University (Hunan Provincial People's Hospital), Changsha 410005, Hunan Province, China
| | - Lv-Zhou Xia
- Department of Gastroenterology, The First Affiliated Hospital of Hunan Normal University (Hunan Provincial People's Hospital), Changsha 410005, Hunan Province, China
| | - Shi-Peng Lu
- Department of Gastroenterology, The First Affiliated Hospital of Hunan Normal University (Hunan Provincial People's Hospital), Changsha 410005, Hunan Province, China
| | - Xiao-Ping Xu
- Department of Gastroenterology, The First Affiliated Hospital of Hunan Normal University (Hunan Provincial People's Hospital), Changsha 410005, Hunan Province, China
| | - Ming-Hao Wu
- Department of Gastroenterology, The First Affiliated Hospital of Hunan Normal University (Hunan Provincial People's Hospital), Changsha 410005, Hunan Province, China
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17
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Kamperidis N, Shah M, Young S, Galimov E, Sweeney S, Arebi N. Use of real-world data to assess the effectiveness of ustekinumab in treating IBD patients: a retrospective linked database study in northwest London. Expert Opin Biol Ther 2023; 23:1317-1329. [PMID: 38009339 DOI: 10.1080/14712598.2023.2279650] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2023] [Accepted: 11/01/2023] [Indexed: 11/28/2023]
Abstract
BACKGROUND Data on the optimum positioning of biologics in the treatment of inflammatory bowel disease (IBD) are limited. RESEARCH DESIGN AND METHODS This was a longitudinal retrospective study of linked health-care data from northwest London, UK, for adults who started ustekinumab for IBD from 1 April 20161 April 2016 to 1 April 20211 April 2021. We compared outcomes by line of therapy (1 vs. 2 or 3+) and age group (18‒59 years or ≥ 60 years). In an analysis of CD patients, we calculated risks of IBD-related hospitalization, IBD-related abdominal surgery, ustekinumab persistence, and switching by line of therapy. RESULTS Of 163 patients screened, 149 were eligible. Age had no effect on outcomes. Elective all-cause hospital admissions were significantly higher when ustekinumab was used as second-line or third-line therapy compared with first-line treatment (p = 0.0048 and p = 0.001, respectively). In CD patients the numbers of hospital admissions were also higher with second-line or third-line therapy (p = 0.040 and p = 0.018, respectively). Use of ustekinumab as third-line therapy significantly increased the risk of IBD-related hospitalization (hazard ratio 2.5, 95% CI 1.1‒5.6, p = 0.029), IBD-related abdominal surgery (9.45, 1.2‒75.7, p = 0.03), and switching (14.6, 1.6‒131.0, p = 0.02). Drug persistence risks did not differ. CONCLUSIONS These findings support the use of ustekinumab as first-line therapy.
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Affiliation(s)
- Nik Kamperidis
- Department of Gastroenterology, St Marks Hospital, London, UK
| | | | | | | | | | - Naila Arebi
- Department of Gastroenterology, St Marks Hospital, London, UK
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18
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Selenized Polymer-Lipid Hybrid Nanoparticles for Oral Delivery of Tripterine with Ameliorative Oral Anti-Enteritis Activity and Bioavailability. Pharmaceutics 2023; 15:pharmaceutics15030821. [PMID: 36986681 PMCID: PMC10059782 DOI: 10.3390/pharmaceutics15030821] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2023] [Revised: 02/15/2023] [Accepted: 03/01/2023] [Indexed: 03/06/2023] Open
Abstract
The oral delivery of insoluble and enterotoxic drugs has been largely plagued by gastrointestinal irritation, side effects, and limited bioavailability. Tripterine (Tri) ranks as the hotspot of anti-inflammatory research other than inferior water-solubility and biocompatibility. This study was intended to develop selenized polymer-lipid hybrid nanoparticles loading Tri (Se@Tri-PLNs) for enteritis intervention by improving its cellular uptake and bioavailability. Se@Tri-PLNs were fabricated by a solvent diffusion-in situ reduction technique and characterized by particle size, ζ potential, morphology, and entrapment efficiency (EE). The cytotoxicity, cellular uptake, oral pharmacokinetics, and in vivo anti-inflammatory effect were evaluated. The resultant Se@Tri-PLNs were 123 nm around in particle size, with a PDI of 0.183, ζ potential of −29.70 mV, and EE of 98.95%. Se@Tri-PLNs exhibited retardant drug release and better stability in the digestive fluids compared with the unmodified counterpart (Tri-PLNs). Moreover, Se@Tri-PLNs manifested higher cellular uptake in Caco-2 cells as evidenced by flow cytometry and confocal microscopy. The oral bioavailability of Tri-PLNs and Se@Tri-PLNs was up to 280% and 397% relative to Tri suspensions, respectively. Furthermore, Se@Tri-PLNs demonstrated more potent in vivo anti-enteritis activity, which resulted in a marked resolution of ulcerative colitis. Polymer-lipid hybrid nanoparticles (PLNs) enabled drug supersaturation in the gut and the sustained release of Tri to facilitate absorption, while selenium surface engineering reinforced the formulation performance and in vivo anti-inflammatory efficacy. The present work provides a proof-of-concept for the combined therapy of inflammatory bowel disease (IBD) using phytomedicine and Se in an integrated nanosystem. Selenized PLNs loading anti-inflammatory phytomedicine may be valuable for the treatment of intractable inflammatory diseases.
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19
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Pavel C, Diculescu M, Constantinescu G, Plotogea OM, Sandru V, Meianu C, Dina I, Pop I, Butuc A, Mihaila M, Stan-Ilie M. Surgery for Inflammatory Bowel Disease in the Era of Biologic Therapy: A Multicenter Experience from Romania. MEDICINA (KAUNAS, LITHUANIA) 2023; 59:337. [PMID: 36837538 PMCID: PMC9963331 DOI: 10.3390/medicina59020337] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/11/2022] [Revised: 02/02/2023] [Accepted: 02/08/2023] [Indexed: 02/12/2023]
Abstract
Background and Objectives: Biologic therapy has fundamentally changed the opportunity of medical treatment to induce and maintain remission in inflammatory bowel disease (IBD). Nevertheless, the rate of surgery is still at a very high rate, profoundly affecting the quality of life. We aimed to analyze surgical cases at three major IBD units in order to identify the main risk factors and the impact of biologic therapy on pre- and postsurgical outcomes. Material and Methods: This was a multicenter retrospective cohort study that included 56 patients with IBD-related surgical interventions from 3 tertiary care hospitals in Bucharest, Romania. The study was conducted between January 2017 and June 2021. All data were retrospectively collected from the medical records of the patients and included the age at diagnosis, age at the time of surgery, IBD type and phenotype, biologic therapy before or/and after surgery, timing of biologic therapy initiation, extraintestinal manifestations, type of surgery (elective/emergency), early and long-term postoperative complications and a history of smoking. Results: A low rate of surgical interventions was noted in our cohort (10.3%), but half of these occurred in the first year after the IBD diagnosis. A total of 48% of the surgical interventions had been performed in an emergency setting, which seemed to be associated with a high rate of long-term postoperative complications. We found no statistically significant differences between IBD patients undergoing treatments with biologics before surgery and patients who did not receive biologics before the surgical intervention in terms of the IBD phenotype, type of surgery and postoperative complications. Conclusion: Our study showed that biologics initiated before the surgical intervention did not influence the postoperative complications. Moreover, we demonstrated that patients with Crohn's disease and no biologics were the most susceptible to having to undergo surgery. Conclusion: In conclusion, the management of patients with IBD requires a multidisciplinary approach that considers an unpredictable evolution.
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Affiliation(s)
- Christopher Pavel
- Department 5, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania
- Department of Gastroenterology, Clinical Emergency Hospital of Bucharest, 014461 Bucharest, Romania
| | - Mircea Diculescu
- Department 5, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania
- Department of Gastroenterology, Fundeni Clinical Institute, 022328 Bucharest, Romania
| | - Gabriel Constantinescu
- Department 5, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania
- Department of Gastroenterology, Clinical Emergency Hospital of Bucharest, 014461 Bucharest, Romania
| | - Oana-Mihaela Plotogea
- Department 5, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania
- Department of Gastroenterology, Clinical Emergency Hospital of Bucharest, 014461 Bucharest, Romania
| | - Vasile Sandru
- Department of Gastroenterology, Clinical Emergency Hospital of Bucharest, 014461 Bucharest, Romania
| | - Corina Meianu
- Department 5, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania
- Department of Gastroenterology, Fundeni Clinical Institute, 022328 Bucharest, Romania
| | - Ion Dina
- Department 5, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania
- Department of Gastroenterology, Sf. Ioan Clinical Emergency Hospital, 042122 Bucharest, Romania
| | - Ioana Pop
- Department of Gastroenterology, Sf. Ioan Clinical Emergency Hospital, 042122 Bucharest, Romania
| | - Andreea Butuc
- Department of Gastroenterology, Clinical Emergency Hospital of Bucharest, 014461 Bucharest, Romania
| | - Mariana Mihaila
- Department of Gastroenterology, Fundeni Clinical Institute, 022328 Bucharest, Romania
| | - Madalina Stan-Ilie
- Department 5, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania
- Department of Gastroenterology, Clinical Emergency Hospital of Bucharest, 014461 Bucharest, Romania
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Pellino G, Armuzzi A. Colectomy rates for ulcerative colitis over time: Navigating the evidence in the era of precision medicine and individualised treatment. Dig Liver Dis 2023; 55:1-2. [DOI: 10.1016/j.dld.2022.09.017] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/12/2022]
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21
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Mannucci A, D'Amico F, El Saadi A, Peyrin-Biroulet L, Danese S. Filgotinib for moderately to severely active ulcerative colitis. Expert Rev Gastroenterol Hepatol 2022; 16:927-940. [PMID: 36278878 DOI: 10.1080/17474124.2022.2138857] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/04/2022]
Abstract
INTRODUCTION Filgotinib is an oral Janus kinase type 1 (JAK1) selective inhibitor with demonstrated efficacy and safety in ulcerative colitis (UC). The aim of this review is to summarize the available evidence on pharmacological characteristics, efficacy, and safety of filgotinib in UC. AREAS COVERED Pubmed, Scopus, and Embase databases were searched for all relevant studies reporting the efficacy and safety of filgotinib in patients with moderate to severe UC. We particularly focused on the risk of zoster infection and venous thromboembolism compared to other JAK inhibitors. EXPERT OPINION Filgotinib has remarkable efficacy, safety, and tolerability profiles in the treatment of moderate-to-severe active UC. It can be used in both biologic-naïve and biologic-experienced patients. The rapid mechanism of action and its oral administration route make it a reliable therapeutic option.
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Affiliation(s)
- Alessandro Mannucci
- Gastroenterology and Gastrointestinal Endoscopy Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy.,Vita-Salute San Raffaele University, Milan, Italy
| | - Ferdinando D'Amico
- Gastroenterology and Gastrointestinal Endoscopy Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy.,Vita-Salute San Raffaele University, Milan, Italy.,Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy
| | | | - Laurent Peyrin-Biroulet
- Department of Gastroenterology, University of Lorraine, CHRU-Nancy, F-54000, Nancy, France.,Department of Gastroenterology, University of Lorraine, Inserm, NGERE, F-54000, Nancy, France
| | - Silvio Danese
- Gastroenterology and Gastrointestinal Endoscopy Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy.,Vita-Salute San Raffaele University, Milan, Italy
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22
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Abstract
Short bowel syndrome (SBS) is a rare disorder characterized by severe intestinal dysfunction leading to malabsorption of macronutrients and micronutrients that often results in permanent need of parenteral nutrition support. Patients can develop SBS because of massive intestinal resection or loss of intestinal function and consequently experience significant morbidity and increased healthcare utilization. The remaining anatomy and length of bowel after intestinal resection have important prognostic and therapeutic implications. Because patients with SBS constitute a heterogenous group, management is complex and multifaceted, involving nutrition support, fluid and electrolyte management, and pharmacologic therapies in particular to control diarrhea. Surgical interventions including intestinal transplantation may be considered in selected individuals. Successful care of these patients is best accomplished by a multidisciplinary team that is experienced in the management of this syndrome.
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Cai Z, Wang S, Li J. Treatment of Inflammatory Bowel Disease: A Comprehensive Review. Front Med (Lausanne) 2021; 8:765474. [PMID: 34988090 PMCID: PMC8720971 DOI: 10.3389/fmed.2021.765474] [Citation(s) in RCA: 248] [Impact Index Per Article: 62.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2021] [Accepted: 11/29/2021] [Indexed: 12/14/2022] Open
Abstract
Inflammatory bowel disease (IBD), as a global disease, has attracted much research interest. Constant research has led to a better understanding of the disease condition and further promoted its management. We here reviewed the conventional and the novel drugs and therapies, as well as the potential ones, which have shown promise in preclinical studies and are likely to be effective future therapies. The conventional treatments aim at controlling symptoms through pharmacotherapy, including aminosalicylates, corticosteroids, immunomodulators, and biologics, with other general measures and/or surgical resection if necessary. However, a considerable fraction of patients do not respond to available treatments or lose response, which calls for new therapeutic strategies. Diverse therapeutic options are emerging, involving small molecules, apheresis therapy, improved intestinal microecology, cell therapy, and exosome therapy. In addition, patient education partly upgrades the efficacy of IBD treatment. Recent advances in the management of IBD have led to a paradigm shift in the treatment goals, from targeting symptom-free daily life to shooting for mucosal healing. In this review, the latest progress in IBD treatment is summarized to understand the advantages, pitfalls, and research prospects of different drugs and therapies and to provide a basis for the clinical decision and further research of IBD.
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Affiliation(s)
- Zhaobei Cai
- Department of General Surgery, The Second Hospital of Jilin University, Changchun, China
- Department of Gastroenterology and Hepatology, Chinese People's Liberation Army General Hospital, Beijing, China
| | - Shu Wang
- Department of Radiotherapy, The Second Hospital of Jilin University, Changchun, China
| | - Jiannan Li
- Department of General Surgery, The Second Hospital of Jilin University, Changchun, China
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Klang E, Barash Y, Soffer S, Shachar E, Lahat A. Trends in inflammatory bowel disease treatment in the past two decades-a high-level text mining analysis of PubMed publications. United European Gastroenterol J 2021; 9:1019-1026. [PMID: 34431607 PMCID: PMC8598961 DOI: 10.1002/ueg2.12138] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/15/2021] [Accepted: 07/04/2021] [Indexed: 12/13/2022] Open
Abstract
AIM Many therapeutic options for inflammatory bowel disease (IBD) emerged during the last 2 decades, along with the rise in disease prevalence and incidence. We aimed at assessing the published literature on different treatment options in that period. Special attention was attributed to specific medication mechanisms and geographic diversity. MATERIALS AND METHODS We have queried PubMed for all available IBD-related entries published during 2000-2020. The following data were extracted for each entry: PubMed unique article ID (PMID), title, publishing journal, abstract text, keywords (if any), and authors' affiliations. Two gastrointestinal specialists decided in consensus on a list of terms to classify entries. The terms belonged to five treatment groups: medical, surgical, dietary, microbiome manipulation, and complementary medicine. The medical and complementary medicine groups were further sub-classified. Annual trends of publications for the years 2000-2020 were plotted for different treatment types. The slopes of publication trends were calculated by fitting regression lines to the annual number of publications. RESULTS Overall, 77,505 IBD entries were published between 2000 and 2020. Medical treatment showed the highest number of total publications 21,540/77,505 (27.8%), followed by surgical 7605/77,505 (9.8%), microbiome research 5260/77,505 (6.8%), dietary 4819/77,505 (6.2%), and complementary medicine treatment 762/77,505 (1.0%). Interestingly, since 2012 there is a steep rise in microbiome publications that outnumbered surgery in the last 2 years. Trend analysis of medical treatment showed that biologics had the steepest slope (57.5, p < 0.001), followed by immunomodulators (4.9, p < 0.001), small molecules (3.9, p < 0.001), and 5-ASA (3.8, p < 0.001). CONCLUSION According to our high-level publications trend analysis, the past 2 decades certainly deserve the reference as the "biologic era", as publications regarding biological therapy outnumbered all other treatment options. Interestingly, though very popular among patients, complementary medicine was not studied with correlation to its' acceptance among patients.
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Affiliation(s)
- Eyal Klang
- Department of Diagnostic ImagingSheba Medical CenterTel HashomerIsrael
- Sackler Medical SchoolTel Aviv UniversityTel AvivIsrael
- DeepVision LabSheba Medical CenterTel HashomerIsrael
| | - Yiftach Barash
- Department of Diagnostic ImagingSheba Medical CenterTel HashomerIsrael
- Sackler Medical SchoolTel Aviv UniversityTel AvivIsrael
- DeepVision LabSheba Medical CenterTel HashomerIsrael
| | - Shelly Soffer
- DeepVision LabSheba Medical CenterTel HashomerIsrael
- Internal Medicine BAssuta Medical CenterAshdodIsrael
- Ben‐Gurion University of the NegevBe'er ShevaIsrael
| | - Eyal Shachar
- Sackler Medical SchoolTel Aviv UniversityTel AvivIsrael
- Department of GastroenterologySheba Medical CenterTel HashomerIsrael
| | - Adi Lahat
- Sackler Medical SchoolTel Aviv UniversityTel AvivIsrael
- Department of GastroenterologySheba Medical CenterTel HashomerIsrael
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25
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Soriano CR, Powell CR, Chiorean MV, Simianu VV. Role of hospitalization for inflammatory bowel disease in the post-biologic era. World J Clin Cases 2021; 9:7632-7642. [PMID: 34621815 PMCID: PMC8462259 DOI: 10.12998/wjcc.v9.i26.7632] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/19/2021] [Revised: 05/17/2021] [Accepted: 08/12/2021] [Indexed: 02/06/2023] Open
Abstract
Treatment for inflammatory bowel disease (IBD) often requires specialized care. While much of IBD care has shifted to the outpatient setting, hospitalizations remain a major site of healthcare utilization and a sizable proportion of patients with inflammatory bowel disease require hospitalization or surgery during their lifetime. In this review, we approach IBD care from the population-level with a specific focus on hospitalization for IBD, including the shifts from inpatient to outpatient care, the balance of emergency and elective hospitalizations, regionalization of specialty IBD care, and contribution of surgery and endoscopy to hospitalized care.
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Affiliation(s)
- Celine R Soriano
- Department of Surgery, Virginia Mason Franciscan Health, Seattle, WA 98101, United States
| | - Charleston R Powell
- Department of Internal Medicine, Madigan Army Medical Center, Tacoma, WA 98431, United States
| | - Michael V Chiorean
- Department of Gastroenterology, Swedish Medical Center, Seattle, WA 98109, United States
| | - Vlad V Simianu
- Department of Surgery, Virginia Mason Franciscan Health, Seattle, WA 98101, United States
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