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Objectives: Chronic liver disease is often associated with testosterone deficiency. However, testosterone replacement does not improve hepatic function or survival with diseased liver. So far, to our knowledge, testosterone replacement therapy after successful livertransplantforfunctional sarcopenia has not been studied. We had 3 goals: (1) define postoperative functional sarcopenia afterlivertransplant with serum testosterone level; (2) examine the role of short-term testosterone replacement therapy with active in-bed exercise of upper and lower extremity joints; and (3) correlate functional sarcopenia with skeletal muscle index and skeletal muscle density in relation to ascites, pleural effusion subtracted body mass index., Materials and Methods: We evaluated 16 liver transplant recipients who had been receiving posttransplanttestosterone replacementtherapy with functional sarcopenia. Preoperative and postoperative demographics and laboratory and radiological data were retrieved; body mass index, skeletal muscle index, and skeletal muscle density were calculated. For this retrospective study, institutional review board approval was obtained before the electronic database was reviewed and analyzed., Results: Mean testosterone level was 28.3 ng/dL (<5% of expected). Twelve patients received 1 dose, and the remaining 4 patients received >1 dose oftestosterone cypionate, 200 mg. Mean hospital stay was 26 days. Seven patients were discharged home, with the remaining patients to a rehabilitation facility or nursing home. One patient died from a cardiac event, and another patient died from recurrent metastatic malignancy. The 1-year and 5-year actuarial patient and graft survival rates were 93.8% and 87.5%, respectively. Overall, 5 patients were sarcopenic by skeletal muscle index, and 6 patients had poor muscle quality by skeletal muscle density., Conclusions: Testosterone deficiency after liver transplant exists with functional sarcopenia. Two- thirds of such recipients have low skeletal muscle index and/or have low skeletal muscle density. Short- term testosterone replacement therapy with in-bed active exercise provides 5-year patient and graft survival of 87.5%.

Background: Hepatopulmonary syndrome affects 10-30% of patients with cirrhosis and portal hypertension. We evaluated the serum angiogenic profile of hepatopulmonary syndrome and assessed the clinical impact of hepatopulmonary syndrome in patients evaluated for liver transplantation., Methods: The Pulmonary Vascular Complications of Liver Disease 2 study was a multicentre, prospective cohort study of adults undergoing their first liver transplantation evaluation. Hepatopulmonary syndrome was defined as an alveolar-arterial oxygen gradient ≥15 mmHg (≥20 mmHg if age >64 years), positive contrast-enhanced transthoracic echocardiography and absence of lung disease., Results: We included 85 patients with hepatopulmonary syndrome and 146 patients without hepatopulmonary syndrome. Patients with hepatopulmonary syndrome had more complications of portal hypertension and slightly higher Model for End-Stage Liver Disease-Na score compared to those without hepatopulmonary syndrome (median (interquartile range) 15 (12-19) versus 14 (10-17), p=0.006). Hepatopulmonary syndrome patients had significantly lower 6-min walk distance and worse functional class. Hepatopulmonary syndrome patients had higher circulating angiopoietin 2, Tie2, tenascin C, tyrosine protein kinase Kit (c-Kit), vascular cell adhesion molecule 1 and von Willebrand factor levels, and lower E-selectin levels. Patients with hepatopulmonary syndrome had an increased risk of death (hazard ratio 1.80, 95% CI 1.03-3.16, p=0.04), which persisted despite adjustment for covariates (hazard ratio 1.79, 95% CI 1.02-3.15, p=0.04). This association did not vary based on levels of oxygenation, reflecting the severity of hepatopulmonary syndrome., Conclusion: Hepatopulmonary syndrome was associated with a profile of abnormal systemic angiogenesis, worse exercise and functional capacity, and an overall increased risk of death., Competing Interests: Conflict of interest: None declared., (Copyright ©The authors 2022. For reproduction rights and permissions contact permissions@ersnet.org.)

Objectives: Newly developed, direct-acting antiviral therapy is effective in over 90% of cases to eradicate hepatitis C virus infection. Direct-acting antiviral therapy is also effective in liver transplant recipients with recurrent hepatitis C virus infection. However, hepatic function after sustained virologic response in transplant recipients is unknown. Here, we aimed to uncover the incidence of hepatic dysfunction in this patient group at our center., Materials and Methods: Our study included 40 consecutive (January 2014 to February 2016) and compliant posttransplant recipients who achieved sustained viral response from direct-acting antiviral therapy. Patients were investigated for incidence and causes of hepatic dysfunction., Results: In our patient group, 4 (10%) experienced hepatic dysfunction with stable baseline immunosuppression, with 2 having drastic increases in alanine aminotransferase at 15 and 32 weeks after direct-acting antiviral therapy. Biopsies showed hepatitis, and both patients were treated with hydrocortisone, which increased their baseline immunosuppression. The 3rd patient had an increase in bilirubin at 21 weeks posttherapy, with biopsy showing macrovascular steatosis. The 4th patient had a rapid increase in bilirubin at 7 weeks after direct-acting antiviral therapy, with biopsy showing significant duct loss., Conclusions: During the study period, 10% of patients experienced hepatic dysfunction after sustained viral response. Presumed causative factors included partial immune reconstitution and nonalcoholic fatty liver disease.

Background: Resident physicians' achievement of professional competencies requires reflective practice skills and faculty coaching. Graduate medical education programs, however, struggle to operationalize these activities., Objective: To (1) describe the process and strategies for implementing an Internal Medicine (IM) resident coaching program that evolved in response to challenges, (2) characterize residents' professional learning plans (PLPs) and their alignment with EPAs, and, (3) examine key lessons learned., Design: The program began in 2013 and involved all postgraduate years (PGY) residents (n = 60, 100%), and 20 faculty coaches who were all IM trained and practicing in an IM-related specialty. One coach was linked with 3-4 residents for three years. Through 1:1 meetings, resident-coach pairs identified professional challenges ('disorienting dilemmas' or 'worst days'), reviewed successes ('best days'), and co-created professional learning plans. Typed summaries were requested following meetings. Coaches met monthly for professional development and to discuss program challenges/successes, which informed programmatic improvements; additionally, a survey was distributed after three program years. Data were analyzed using quantitative and qualitative methodologies., Results: Disorienting dilemmas and professional learning plans mapped to all 16 EPAs and four additional themes: work-life balance, career planning, teaching skills, and research/scholarship. The most-frequently mapped topics included: PGY1 - leading and working within interprofessional care teams (EPA 10), research and scholarship, and work-life balance; PGY2 - improving quality of care (EPA 13), demonstrating personal habits of lifelong learning (EPA15), and research and scholarship; PGY3 - lifelong learning (EPA15); career planning was common across all years., Conclusions: Lessons learned included challenges in coordination of observations, identifying disorienting dilemmas, and creating a shared mental model between residents, faculty, and program leadership. The coaching program resulted in professional learning plans aligned with IM EPAs, in addition to other professional development topics. Operationalization of aspects of these results can inform the development of similar programs in residency education.

Introduction: Capsule endoscopy has been suggested as a potential alternative to endoscopy for detection of esophagogastric varices and severe portal hypertensive gastropathy (PHG). The aim of the study was to determine whether PillCam esophageal capsule endoscopy could replace endoscopy for screening purposes., Material and Methods: Sixty-two patients with cirrhosis with no previous variceal bleeding had PillCam capsule endoscopy and video endoscopy performed on the same day. Sensitivity, specificity, and positive and negative predictive values (PPV, NPV) of capsule endoscopy were compared to endoscopy for the presence and severity of esophageal and gastric varices, PHG and the need for primary prophylaxis. Patients' preference was assessed by a questionnaire., Results: Four (6%) patients were unable to swallow the capsule. Sensitivity, specificity, PPV and NPV of capsule endoscopy for detecting any esophageal varices (92%, 50%, 92%, 50%), large varices (55%, 91%, 75%, 80%), variceal red signs (58%, 87%, 69%, 80%), PHG (95%, 50%, 95%, 50%), and the need for primary prophylaxis (91%, 57%, 78%, 80%) were not optimal, with only moderate agreement (κ) between capsule and upper GI endoscopy. Had only a capsule endoscopy been performed, 12 (21.4%) patients would have received inappropriate treatment. Capsule endoscopy also failed to detect (0/13) gastric varices. The majority of patients ranked capsule endoscopy as more convenient (69%) and their preferred (61%) method., Conclusions: Despite the preference expressed by patients for capsule endoscopy, we believe that upper GI endoscopy should remain the preferred screening method for primary prophylaxis.

Reduction of immunosuppression (RI) is commonly used to treat posttransplant lymphoproliferative disorder (PTLD) in solid organ transplant recipients. We investigated the efficacy, safety and predictors of response to RI in adult patients with PTLD. Sixty-seven patients were managed with RI alone and 30 patients were treated with surgical excision followed by adjuvant RI. The response rate to RI alone was 45% (complete response-37%, partial response-8%). The relapse rate in complete responders was 17%. Adjuvant RI resulted in a 27% relapse rate. The acute rejection rate following RI-containing strategies was 32% and a second transplant was feasible without relapse of PTLD. The median survival was 44 months in patients treated with RI alone and 9.5 months in patients who remained on full immunosuppression (p = 0.07). Bulky disease, advanced stage and older age predicted lack of response to RI. Survival analysis demonstrated predictors of poor outcome-age, dyspnea, B symptoms, LDH level, hepatitis C, bone marrow and liver involvement. Patients with none or one of these factors had a 3-year overall survival of 100% and 79%, respectively. These findings support the use of RI alone in low-risk PTLD and suggest factors that predict response and survival., (©2011 The Authors Journal compilation©2011 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Cardiovascular (CV) disease has a significant impact on post-liver transplantation (LT) survival. Finding surrogate markers for occult CV disease would improve CV assessment in the LT evaluation. This study was designed to determine the prevalence of microvascular disease (MVD) and the utility of both microalbuminuria and the homeostatic model for insulin resistance (HOMA-IR) for assessing the presence of MVD in potential LT recipients. In this study, we examined the prevalence of MVD in 72 diabetics and 71 nondiabetics; both groups were matched for age, sex, race, and etiology of cirrhosis while awaiting LT. We prospectively collected data including fasting serum insulin and glucose levels, urine creatinine and microalbumin, and macrovascular and microvascular complications. MVD was present in 58 (40.5%) patients; MVD was more common in diabetics (n = 45, 62.5%) than nondiabetics (n = 13, 18.3%). The presence of diabetes mellitus (DM; P = 0.03), insulin use (P = 0.002), and duration (months) of DM (85.3 +/- 96.1 versus 22.1 +/- 46.3, P < 0.0001), hypertension (51.3 +/- 101.5 versus 22.7 +/- 58.2, P = 0.03), and hypertriglyceridemia (7.2 +/- 17.4 versus 3.8 +/- 18.5, P = 0.04) were associated with MVD. Significant microalbuminuria had a sensitivity of 85%, a specificity of 100%, and a positive predictive value of 100% for the presence of MVD. HOMA-IR also was associated with MVD (P = 0.0001). In conclusion, at our center, 62.5% of DM patients and 18% of non-DM patients awaiting LT have MVD. Patients with DM, significant microalbuminuria, or an elevated HOMA-IR should undergo rigorous CV assessment prior to LT., ((c) 2009 AASLD.)

It has been suggested that the post-liver transplantation (LT) survival rate of patients with hepatitis C virus infection (HCV) has declined in recent years. To compare the outcome of LT in patients with HCV at various time intervals between 1991 and 2001, we used United Network for Organ Sharing data to compare the post-LT survival of adult patients (age >18 years) with HCV with those without HCV. Of the 37,101 patients who underwent LT during the study period, 28,193 patients (HCV 7,459 and 20,734 non-HCV) were eligible for the study. On the basis of the time of transplantation, patients were divided into 3 groups: 1991-1993 (period 1), 1994-1997 (period 2), and 1998-2001 (period 3). The patient and graft survival rates were adjusted for other known confounding variables that influenced outcomes. The 3-year patient survival rate was lower in HCV patients compared with non-HCV recipients (78.5% vs. 81.4%, hazard ratio 1.14, 95% confidence interval 1.05-1.23, P = 0.001). The graft (72.8%, 71.0%, and 69.8%) and patient (77.4%, 79.6%, and 78.5%) survival of HCV patients remained unchanged during study periods 1-3, respectively. However, the graft and patient survival rates of non-HCV recipients improved markedly during study periods 2 and 3 compared with period 1. The graft and patient survival has remained unchanged between 1991 and 2001 in HCV recipients, but during the same period, there was a great improvement in survival among non-HCV recipients.