Sleep disturbances in chronic liver disease.

Sleep disturbances are common in chronic liver disease and significantly impact patient outcomes and quality of life. The severity and nature of sleep disturbances vary by liver disease etiology and severity. While there is ongoing research into the association between liver disease and sleep-wake dysfunction, the underlying pathophysiology varies and, in many cases, is poorly understood. Liver disease is associated with alterations in thermoregulation, inflammation, and physical activity, and is associated with disease-specific complications, such as HE, that may directly affect sleep. In this article, we review the relevant pathophysiologic processes, disease-specific sleep-wake disturbances, and clinical management of CLD-associated sleep-wake disturbances.

Obesity: A Review of Pathophysiology and Classification.

Obesity is a chronic, multifactorial, and morbid disease. In the United States, 69% of adults are overweight or have obesity, and the global prevalence of obesity is increasing. Obesity is influenced by genetic, neurologic, metabolic, enteric, and behavioral processes. It remains a key modifiable risk factor for many comorbid diseases, including cardiovascular disease, diabetes mellitus, and cancer. Whereas there are recent and significant advances in obesity therapy, including diets, lifestyle modifications, pharmacotherapies, endoscopic procedures, and bariatric surgeries, there is an immense need for a better understanding of the heterogeneity in the pathophysiologic process of obesity and outcomes. Here we review salient pathophysiologic mechanisms underlying the development and morbidity of obesity as well as pathophysiologically based classification systems that inform current obesity management and may inform improved and individualized management in the future.

Hemosuccus Pancreaticus: Diagnostic Pitfalls of a Rare Condition.

The combination of cirrhosis and chronic pancreatitis is rare and poses increased risk of hemorrhage requiring close clinical monitoring. We present a patient with history of alcohol-associated cirrhosis and chronic pancreatitis who was admitted to the intensive care unit with clinical hemorrhage believed secondary to epistaxis. After initial delay, esophagogastroduodenoscopy ultimately found blood and clots evacuating through the ampulla consistent with hemosuccus pancreaticus confirmed with computed tomography angiography. The patient ultimately improved with coil and gel foam vascular embolization. This case highlights the dangers of early diagnostic closure and presents a rare finding of hemosuccus without pseudoaneurysm formation.

Effects of Heterozygous Variants in the Leptin-Melanocortin Pathway on Roux-en-Y Gastric Bypass Outcomes: a 15-Year Case-Control Study.

INTRODUCTION: Heterozygous variants in the leptin-melanocortin pathway are associated with obesity. However, their effect on the long-term outcomes after Roux-en-Y gastric bypass (RYGB) is still unknown. METHODS: In this matched case-control study, 701 participants from the Mayo Clinic Biobank with a history of RYGB were genotyped. Sixty-three patients had a heterozygous variant in the leptin-melanocortin pathway. After excluding patients with potential confounders, carriers were randomly matched (on sex, age, body mass index [BMI], and years since surgery) with two non-carrier controls. The electronic medical record of carriers and matched non-carriers was reviewed for up to 15 years after RYGB. RESULTS: A total of 50 carriers and 100 matched non-carriers with a history of RYGB were included in the study. Seven different genes (LEPR, PCSK1, POMC, SH2B1, SRC1, MC4R, and SIM1) in the leptin-melanocortin pathway were identified. At the time of surgery, the mean age was 50.8 ± 10.6 years, BMI 45.6 ± 7.3 kg/m2, and 79% women. There were no differences in postoperative years of follow-up, Roux limb length, or gastric pouch size between groups. Fifteen years after RYGB, the percentage of total body weight loss (%TBWL) in carriers was - 16.6 ± 10.7 compared with - 28.7 ± 12.9 in non-carriers (diff = 12.1%; 95% CI, 4.8 to 19.3) and the percentage of weight regain after maximum weight loss was 52.7 ± 29.7 in carriers compared with 29.8 ± 20.7 in non-carriers (diff = 22.9%; 95% CI, 5.3 to 40.5). The nadir %TBWL was lower - 32.1 ± 8.1 in carriers compared with - 36.8 ± 10.4 in non-carriers (diff = 4.8%; 95% CI 1.8 to 7.8). CONCLUSIONS: Carriers of a heterozygous variant in the leptin-melanocortin pathway have a progressive and significant weight regain in the mid- and long-term after RYGB. Genotyping patients experiencing significant weight regain after RYGB could help implement multidisciplinary and individualized weight loss interventions to improve weight maintenance after surgery.

A comparison between weight loss outcomes with anti-obesity medications before and during Covid-19 pandemic at a tertiary weight management center.

Background: /Objectives: Obesity is a risk factor for COVID-19 infection severity and mortality. Anti-obesity medications (AOM) are effective for weight loss. However, weight loss outcomes with AOM during the COVID-19 pandemic are yet to be described. Subjects: /Methods: Between January 1, 2016, and June 30, 2021, a total of 966 patients were prescribed long-term FDA-approved AOMs at the Mayo Clinic. From these patients, 711 patients did not meet inclusion criteria. A total of 255 patients were included. Interventions/methods: We performed a retrospective systematic review of electronic medical records and included patients who started a long-term FDA-approved AOM. We excluded patients with history of bariatric procedure, AOM prescription with lorcaserin, orlistat, semaglutide (approved for weight loss after the pandemic), or phentermine (short-term AOM), those taking ≥2 AOMs, <3 months of prescribed AOM, and/or pregnancy. Analysis was divided by 1)preCOVID-19: those who started an AOM before COVID-19 restrictions, 2)COVID-19: those who started an AOM during first quarter of 2020 after the establishment of COVID-19 restrictions. Our primary endpoint was the total body weight loss percentage (%TBWL) at 3, 6, and 12 months after AOM initiation. Results: There was a statistical difference in TBWL% between the preCOVID-19 and COVID-19 group: 5.3 ± 3.5% vs 4 ± 3.0% (95% CI -2.4 to -0.2; p = 0.02) and 9.7 ± 7.2% vs 6.2 ± 4.7% (95% CI -5.7 to -1.3; p = 0.002) at 3 and 12 months, respectively. At 6 months, the TBWL% was 7.1 for the preCOVID-19 group compared to 6.2% for the COVID-19 (95% CI -2.5 to 0.7; p = 0.25). Conclusion: With the possible exception of liraglutide, this study shows that weight loss outcomes to AOMs were inferior when prescribed during the routine clinical practice throughout COVID-19 pandemic, compared to the outcomes observed prior to the COVID-19 pandemic.

Validation of choledocholithiasis predictors from the "2019 ASGE Guideline for the role of endoscopy in the evaluation and management of choledocholithiasis."

BACKGROUND AND AIMS: Identifying patients likely to have CDL is an important clinical dilemma because endoscopic retrograde cholangiopancreatography (ERCP), carries a 5-7% risk of adverse events. The purpose of this study was to compare the diagnostic test performance of the 2010 and 2019 ASGE criteria used to help risk stratify patients with suspected CDL. METHODS: Consecutive patients evaluated for possible CDL from 2013 to 2019 were identified from surgical, endoscopic, and radiologic databases at a single academic center. Inclusion criteria included all patients who underwent ERCP and/or cholecystectomy with intraoperative cholangiogram (IOC) for suspected CDL. We calculated the diagnostic test performance of criteria from both guidelines and compared their discrimination using the receiver operator curve. Univariate and multivariate analysis was used to identify the strongest component predictors. RESULTS: 1098 patients [age 57.9 ± 19.0 years, 62.8% (690) F] were included. 66.3% (728) were found to have CDL on ERCP and/or IOC. When using the 2019 guidelines, the sensitivity, specificity, PPV, NPV, and accuracy are 65.8, 78.9, 86.3, 54.1, and 70.4%, respectively. Using the 2010 guidelines, the sensitivity, specificity, PPV, NPV, and accuracy are 50.5, 78.9, 82.5, 44.8, and 60.1%, respectively. The AUC for high-risk criteria using the 2019 guidelines [0.726 (0.695, 0.758)] was greater than for the 2010 guidelines [0.647 (0.614, 0.681)]. The key difference providing the increased discrimination was the inclusion of stones on any imaging modality, which increased the sensitivity to 55.0% from 29.1%. Not including CDL on imaging or cholangitis, a dilated CBD was the strongest individual predictor of CDL on multivariate analysis (OR 3.70, CI 2.80, 4.89). CONCLUSION: Compared to 2010, the 2019 high-risk criterion improves diagnostic test performance, but still performs suboptimally. Less invasive tests, such as EUS or MRCP, should be considered in patients with suspected CDL prior to ERCP.