Mouchli, Mohamad

With longer survival of patients with primary sclerosing cholangitis (PSC) undergoing liver transplantation (LT), the frequency and risk factors associated with vascular and biliary complications in the allograft and the impact on long-term outcomes are poorly understood. To assess frequency and risk factors for long-term outcomes in patients after LT for PSC, all recipients of LT for advanced stage PSC for a non-cholangiocarcinoma indication from 1984 to 2012, with follow-up through March 2022 (>10+ y follow-up), were identified. One-, 5-, and 10-year cumulative risks of complications were estimated using the Aalen-Johansen method, where death was considered a competing risk. Two hundred ninety-three patients (mean age, 47.3 ± 12 y) formed our study cohort. One hundred and thirty-four patients received LT before 1995, and 159 were transplanted after 1995. Over a median (IQR) follow-up of 15.0 (10.3–22.1) years, LT was complicated by hepatic artery thrombosis (N = 30), portal vein stenosis/thrombosis (N = 48), biliary leak (N = 47), biliary strictures (N = 87), recurrent PSC (N=107), and graft failure (N=70). The 1-, 5-, 10-, and 15-year cumulative incidence of recurrent PSC was 1.0%, 8.0%, 23.5%, and 34.3%, respectively. The type of donor and older donor age were associated with an increased risk of biliary strictures. Donor age >60 years was associated with an increased risk of recurrent PSC. Long-term patient and graft survival have not changed significantly for patients transplanted for PSC. Controlling transplant-related factors, such as donor age, prompt identification of vascular and biliary complications early, and long-term rigorous follow-up, is recommended to continue to improve on these outcomes.

AbstractBackgroundNeostigmine, an acetyl cholinesterase inhibitor, stimulates colonic motor activity and may induce vagally mediated cardiovascular effects. Our aim was to evaluate effects of i.v. neostigmine on colonic compliance and its safety in patients with chronic constipation.MethodsWe retrospectively reviewed medical records of a selected group of 144 outpatients with chronic constipation who were refractory to treatment. These patients had undergone intracolonic motility and compliance measurements with an infinitely compliant balloon linked to a barostat. Data abstracted included barostat balloon mean volumes with increases in pressure (4 mmHg steps from 0 to 44 mmHg) before and after i.v. neostigmine. Vital signs and oxygen saturation before and after neostigmine were recorded.Key ResultsOf the 144 patients, 133 were female, mean age was 41.0 ± 15.4 years (SD), and duration of constipation was 12.9 ± 13.8 years. Among patients who had undergone colonic transit measurement by scintigraphy, the overall colonic transit at 24 h (geometric center, GC24 [n = 115]) was 1.5 ± 0.7 (normal >1.3), and at 48 h (GC48 [n = 75]) it was 2.3 ± 0.9 (normal >1.9). Neostigmine decreased colonic compliance at lower distension pressures (e.g., 12 and 20 mmHg [both p < 0.001]), but not at 40 mmHg. There were expected minor changes in vital signs in response to neostigmine in 144 patients; however, one patient developed unresponsiveness, significant bradycardia, hypotension, and muscular rigidity that responded to 400 mcg i.v. atropine.Conclusions & InferencesNeostigmine significantly decreases colonic compliance in patients with refractory chronic constipation. Symptomatic bradycardia in response to neostigmine should be promptly reversed with atropine.

Abstract Background Gastrointestinal ( GI ) manifestations are found in Ehlers Danlos syndrome ( EDS ) hypermobility subtype ( HM ). We aimed to assess associations between EDS HM and other EDS subtypes with GI manifestations. Methods We reviewed medical records of EDS patients evaluated at Mayo Clinic's Medical Genetics Clinic 1994–2013. We extracted information regarding EDS subtypes, GI manifestations, and treatments. Key Results We identified 687 patients; 378 (56%) had associated GI manifestations (female 86.8%, diagnosis mean age 29.6 years). Of the patients identified, 58.9% (43/73) had EDS classic, 57.5% (271/471) EDS HM , 47.3% (27/57) EDS vascular subtypes. In addition, 86 patients had EDS that could not be classified in any of those three subtypes. Commonest GI symptoms were: abdominal pain (56.1%), nausea (42.3%), constipation (38.6%), heartburn (37.6%), and irritable bowel syndrome‐like symptoms (27.5%). Many GI symptoms were commoner in EDS HM than the other subtypes together. Among 37.8% of the 378 patients who underwent esophagogastroduodenoscopy, the commonest abnormalities were gastritis, hiatal hernia and reflux esophagitis. Abnormal gastric emptying was observed in 22.3% (17/76): 11.8% delayed and 10.5% accelerated. Colonic transit was abnormal in 28.3% (13/46): 19.6% delayed and 8.7% accelerated. Rectal evacuation disorder was confirmed in 18/30 patients who underwent anorectal manometry. Angiography showed aneurysms in abdominal vessels in EDS vascular type. Proton pump inhibitors (38%) and drugs for constipation (23%) were the most commonly used medications. A minority underwent colectomy (2.9%) or small bowel surgery (4%). Conclusions & Inferences EDS HM and other subtypes should be considered in patients with chronic functional GI symptoms and abdominal vascular lesions.