Evaluation of the United Kingdom-Primary Biliary Cholangitis and Global Primary Biliary Cholangitis Group Prognostic Models for Primary Biliary Cholangitis Patients Treated with Ursodeoxycholic Acid in the U.S. Population

JGH Open: An open access journal of gastroenterology and hepatology published by Journal of Gastroenterology and Hepatology Foundation and John Wiley and Sons Australia, Ltd. Background and Aim: The United Kingdom-primary biliary cholangitis (UK-PBC) and global primary biliary cholangitis group (GLOBE) prognostic models have been recently developed to predict long-term outcomes in primary biliary cholangitis (PBC). However, these predictive scores have not yet been well evaluated in the U.S. population. Methods: We retrospectively reviewed newly diagnosed PBC patients at the Cleveland Clinic between November 1998 and February 2017. Adverse events were defined as liver transplantation, liver-related mortality, and all-cause mortality. Transplant-free survival (TFS) was estimated using the Kaplan–Meier method. Predictive performances of all prognostic models were evaluated using the C-statistic. Results: We identified 352 patients who used ursodeoxycholic acid therapy. Of them, 311 (88.4%) only had PBC, while 41 (11.6%) were diagnosed with PBC-autoimmune hepatitis overlap. A total of 22 (6%), 47 (13%), and 55 (16%) patients had adverse events within 5, 10, and 15 years after diagnosis, respectively. In patients with PBC only, the C-statistic in predicting 15-year adverse events was 0.75 per GLOBE compared to 0.74 per UK-PBC (P = 0.94), 0.73 per Rotterdam (P = 0.44), 0.66 per Barcelona (P = 0.004), 0.65 per Paris 1 (P = 0.005), 0.62 per Paris 2 (P \u3c 0.0001), 0.60 per Toronto (P \u3c 0.0001), and 0.60 per Mayo (P \u3c 0.0001) scores. Median follow-up was 9.2 years. Ten-year TFS for patients who had optimal versus suboptimal treatment response was 92 versus 74% per Paris 1 (P \u3c 0.0001), 95 versus 79% per Paris 2 (P = 0.0002), 93 versus 65% per Barcelona (P \u3c 0.0001), and 96 versus 68% per Rotterdam (P \u3c 0.0001) risk scores, respectively. Conclusion: In our cohort of PBC patients, the UK-PBC and GLOBE scores were both accurate and reasonably valid prognostic models in the U.S. population

Duvelisib for critically ill patients with coronavirus disease 2019: An investigator-initiated, randomized, placebo-controlled, double-blind pilot trial

BACKGROUND: Despite improvements in prevention and treatment, severe coronavirus disease 2019 (COVID-19) is associated with high mortality. Phosphoinositide 3-kinase (PI3K) pathways contribute to cytokine and cell-mediated lung inflammation. We conducted a randomized, placebo-controlled, double-blind pilot trial to determine the feasibility, safety, and preliminary activity of duvelisib, a PI3Kδγ inhibitor, for the treatment of COVID-19 critical illness. METHODS: We enrolled adults aged ≥18 years with a primary diagnosis of COVID-19 with hypoxic respiratory failure, shock, and/or new cardiac disease, without improvement after at least 48 hours of corticosteroid. Participants received duvelisib (25 mg) or placebo for up to 10 days. Participants had daily semi-quantitative viral load measurements performed. Dose modifications were protocol driven due to adverse events (AEs) or logarithmic change in viral load. The primary endpoint was 28-day overall survival (OS). Secondary endpoints included hospital and intensive care unit length of stay, 60-day OS, and duration of critical care interventions. Safety endpoints included viral kinetics and AEs. Exploratory endpoints included serial cytokine measurements and cytometric analysis. RESULTS: Fifteen patients were treated in the duvelisib cohort, and 13 in the placebo cohort. OS at 28 days was 67% (95% confidence interval [CI], 38%-88%) compared to 62% (95% CI, 32%-86%) for placebo ( CONCLUSIONS: In this pilot study, duvelisib did not significantly improve 28-day OS compared to placebo for severe COVID-19. Duvelisib appeared safe in this critically ill population and was associated with reduction in cytokines implicated in COVID-19 and acute respiratory distress syndrome, supporting further investigation. CLINICAL TRIALS REGISTRATION: NCT04372602

Etiology of and Predictive Factors for Chronic Intestinal Failure Requiring Long Term Parenteral Support in the Last Two Decades: A Retrospective Study

Background and aims: Chronic intestinal failure (CIF) has been long-recognized, however the underlying etiology and risk factors have not been historically well-studied. We aim to study the underlying etiologies of CIF and predictive factors for long-term parenteral support (PS). Methods: We retrospectively identified patients with newly diagnosed CIF who received PS to maintain nutrition at the Cleveland Clinic between 2000 and 2017. Long-term PS was defined as a duration of more than 3 months. Univariable and multivariable logistic regression analyses were performed to identify the predictors of the need for long-term PS. Results: We identified 350 patients with CIF, 150 (43%) and 200 (57%) were diagnosed before and after 2010, respectively. The most common etiology was Crohn\u27s disease (CD) in both cohorts (34.7% versus 30.5%, p = 0.41). Graft-versus-host-disease (GVHD) was a less frequent cause of CIF after 2010 (12.7% versus 2.5%, p = 0.0002). The type of PS was mostly total parenteral nutrition before and after 2010, 95% and 96%, respectively (p = 0.55). On univariable analysis, absence of ileocecal valve (p \u3c 0.0001), ischemic bowel disease (p = 0.009), and whole colon resection (p = 0.033) were associated with the need for long-term PS. On multivariable analysis, absence of ileocecal valve (OR 2.19, p = 0.011) and ischemic bowel disease (OR 3.04, p = 0.003) remained statistically significant predictors of long-term PS. Conclusion: In our cohort of patients with CIF, CD remains the leading etiology over the last 20 years, whereas GVHD is less common after 2010. The absence of ileocecal valve and ischemic bowel disease were reliable predictive factors for requiring long-term PS

Effects of Probiotics on Intestinal Failure–Associated Liver Disease in Adult Patients Receiving Prolonged Parenteral Support: A Tertiary Care Center Experience

Background: It has been hypothesized that dysbiosis plays a significant role in the pathogenesis of intestinal failure–associated liver disease (IFALD). Therefore, we aimed to investigate the effect of probiotics on IFALD in patients receiving parenteral support, namely home parenteral nutrition (HPN) and home intravenous fluids (HIVFs). Methods: We retrospectively reviewed charts of patients with intestinal failure who received HPN or HIVF for \u3e2 weeks at our tertiary center between January 2005 and August 2016. We excluded patients \u3c18 years of age, patients with other causes of liver disease, patients who used probiotics for \u3c30 days, patients with \u3c6 months\u27 follow-up, and those who had long-term antibiotic use (\u3e30 days). Bivariable and multivariable logistic regression analyses were used in this study. Results: A total of 282 patients who received parenteral support were included. Eighty-five percent of our sample received PN. A total of 78 (27.7%) patients used probiotics. The prevalence of IFALD in patients who used probiotics was 35.9% vs 54.4% in patients who did not use probiotics, P =.005. In multivariable analysis, only small-bowel length of 10-90 cm and HPN use showed a significant impact on IFALD, odds ratio (OR) = 4.394 (95% confidence interval [CI], 1.635-11.814; P =.003) and OR = 4.502 (95% CI 1.412-14.351; P =.011), respectively. Conclusion: Our study revealed that the prevalence of IFALD was comparable among the probiotic users and nonusers. Only small bowel length of 1090 cm and HPN use showed a significant impact on IFALD

Effects of Probiotics on Intestinal Failure–Associated Liver Disease in Adult Patients Receiving Prolonged Parenteral Support: A Tertiary Care Center Experience

Background: It has been hypothesized that dysbiosis plays a significant role in the pathogenesis of intestinal failure–associated liver disease (IFALD). Therefore, we aimed to investigate the effect of probiotics on IFALD in patients receiving parenteral support, namely home parenteral nutrition (HPN) and home intravenous fluids (HIVFs). Methods: We retrospectively reviewed charts of patients with intestinal failure who received HPN or HIVF for \u3e2 weeks at our tertiary center between January 2005 and August 2016. We excluded patients \u3c18 years of age, patients with other causes of liver disease, patients who used probiotics for \u3c30 days, patients with \u3c6 months\u27 follow-up, and those who had long-term antibiotic use (\u3e30 days). Bivariable and multivariable logistic regression analyses were used in this study. Results: A total of 282 patients who received parenteral support were included. Eighty-five percent of our sample received PN. A total of 78 (27.7%) patients used probiotics. The prevalence of IFALD in patients who used probiotics was 35.9% vs 54.4% in patients who did not use probiotics, P =.005. In multivariable analysis, only small-bowel length of 10-90 cm and HPN use showed a significant impact on IFALD, odds ratio (OR) = 4.394 (95% confidence interval [CI], 1.635-11.814; P =.003) and OR = 4.502 (95% CI 1.412-14.351; P =.011), respectively. Conclusion: Our study revealed that the prevalence of IFALD was comparable among the probiotic users and nonusers. Only small bowel length of 1090 cm and HPN use showed a significant impact on IFALD

Prevalence and Predictors of Gastrointestinal Dysmotility in Patients with Hypermobile Ehlers-Danlos Syndrome: A Tertiary Care Center Experience

Introduction Ehlers-Danlos syndrome (EDS), specifically the hypermobility type (hEDS), is associated with a variety of gastrointestinal (GI) conditions. This study aims to evaluate the prevalence of and factors associated with gut dysmotility in patients with hEDS. Methods This is a retrospective study of hEDS patients conducted at the Cleveland Clinic\u27s Center for Personalized Genetic Healthcare between January 2007 and December 2017. Demographics, GI motility testing, endoscopic, and imaging data were extracted from the patients\u27 charts. Results A total of 218 patients with hEDS were identified. Among them, 136 (62.3%) patients had at least one GI symptom at the time of EDS diagnosis. Motility testing was performed and reported in 42 (19.2%) patients. Out of them, five (11.9%) had esophageal dysmotility, 18 (42.8%) had gastroparesis, five (11.9%) had small bowel/colon altered transit time, and four (9.5%) had global dysmotility. In univariable analysis, patients with postural orthostatic tachycardia syndrome (POTS) [odds ratio (OR): 8.88, 95% CI: 3.69-24.9, p\u3c0.0001], fibromyalgia (OR: 4.43, 95% CI: 2.04-10.1, p=0.0002), history of irritable bowel syndrome (OR: 5.01, 95% CI: 2.31-11.2, p\u3c0.0001), and gastroesophageal reflux disease (OR: 3.33, 95% CI: 1.55-7.44, p=0.002) were more likely to be diagnosed with GI dysmotility. On multivariable analysis, only POTS (OR: 5.74, 95% CI: 2.25-16.7, p=0.0005) was significantly associated with an increased likelihood of GI dysmotility. Conclusions This study suggests that GI symptoms are relatively common among patients with hEDS. Of the patients tested for dysmotility, 76.2% were found to have some form of dysmotility. POTS was found to be an independent predictive factor for GI dysmotility