Pulmonary Complications of Everolimus in Liver Transplant Patients: A 10-Year Experience.

This retrospective study aims to evaluate the safety of everolimus when used as part of the immunosuppression regimen in patients who underwent liver transplant from 2009 to 2019 at a tertiary liver transplant center. Patients were divided into two groups: those who received everolimus as part of the post-transplant regimen and those who did not. The primary safety outcome measured was the development of new pulmonary complications that had been associated with everolimus use in prior studies. Lung function was determined by pulmonary function tests if available or CT scans of the chest. Secondary outcomes measured included everolimus discontinuation rates and survival rates. During the study period, 450 patients underwent liver transplant; 35% of patients received everolimus (n=156) and 65% of patients did not receive everolimus (n=292). Primary safety outcome of pulmonary complications was seen in 3.9% of patients who received everolimus (n=6) and 6.3% of the control group patients who did not receive everolimus (n=19). The association between everolimus use and new pulmonary complications was not significant with a chi-square statistic of 1.33 (p=0.249). Overall, 51.3% of patients who received everolimus during their post-transplant course discontinued the medication (n=80). Everolimus is safe from a pulmonary toxicity standpoint in liver transplant immunosuppression regimens as there was no significant difference found in pulmonary complications between patients who received the medication and those who did not.

The Health Care Burden of Hepatic Encephalopathy.

Hepatic encephalopathy-a common and debilitating complication of cirrhosis-results in major health care burden on both patients and caregivers through direct and indirect costs. In addition to risk of falls, inability to work and drive, patients with hepatic encephalopathy often require hospital admission (and often readmission), and many require subacute care following hospitalization. The costs and psychological impact of liver transplantation often ensue. As the prevalence of chronic liver disease increases throughout the United States, the health care burden of hepatic encephalopathy will continue to grow.

Nutrient Drink Test to Assess Gastric Accommodation in Cyclic Vomiting Syndrome: Single-blinded Parallel Grouped Prospective Study.

Background/Aims: Cyclic vomiting syndrome (CVS) is characterized by episodes of nausea and vomiting, separated by symptom-free intervals. The pathogenesis of CVS is poorly understood. Limited data exist on evaluating impaired gastric accommodation as a mechanistic means for symptoms. We aim to determine if CVS patients demonstrate impaired gastric accommodation applying a nutrient drink test (NDT) protocol. Methods: Through this single-blinded pilot clinical trial, patients with CVS per Rome IV critera and healthy controls were assessed for presence of impaired gastric accommodation by administering an established NDT protocol. Statistical analysis was performed, with data presented as medians and interquartile range. Results: Eleven CVS patients and 15 healthy controls participated in the study between January 2018 and October 2018. Median age was 42.0 years and 37.0 years; majority of subjects were female, 72.7% and 73.3%, respectively. Demographics were similar between CVS and healthy controls. Almost all healthy controls (93.3%) ingested the complete 500 mL protocol, whereas a smaller proportion (72.7%) were able to complete all 4 doses in the CVS group (P = 0.188). Post-prandial visual analogue scale scores of nausea and abdominal pain were found to be significantly higher in CVS patients compared to healthy controls. Conclusions: To our knowledge, this is the first NDT protocol in CVS evaluating the role of impaired gastric accommodation and hypersensitivity as a possible pathophysiologic mechanism. Findings from this study suggest the presence of gastric hypersensitivity in a subset of CVS patients. These results provide the foundational data necessary for future larger testing of NDT and diagnostic accuracy in CVS.

An Unusual Case of a Pharyngeal Fistula to the Cervical Spine Causing Osteomyelitis.

SIGNIFICANCE STATEMENT: Pharyngeal fistulas to the cervical spine resulting in vertebral osteomyelitis are a rare, yet clinically important, complication of total laryngectomy performed in conjunction with chemoradiotherapy or radiation therapy. This complication is likely underdiagnosed and can have a high mortality rate. It is very important that clinicians are aware of this complication as early diagnosis and management may improve patient outcomes.

Video Consent for Colonoscopy Improves Knowledge Retention and Patient Satisfaction: A Randomized Controlled Study.

BACKGROUND AND AIM: Informed consent for endoscopy is variable across institutions and remains understudied in gastrointestinal endoscopy. This study aims to standardize informed consent for screening and diagnostic colonoscopies with a supplemental video tool that includes the key components of informed consent. METHODS: A video tool was developed that incorporated the key components of informed consent for colonoscopy. In addition, a 7-question survey was developed to query patients on core aspects of informed consent and satisfaction with the informed consent process. Patients undergoing elective outpatient colonoscopy with conscious sedation were randomized to traditional consent or consent with the addition of a video tool. A pilot study determined the sample size. Traditional consent was standard of practice before the procedure. Patients in the video tool group watched the video tool in the preprocedure area followed by traditional consent. Both groups had the opportunity to address questions with the attending physician before the procedure. All patients were contacted 1 to 2 days following the colonoscopy to answer the question survey. RESULTS: A total of 110 patients were eligible for participation, and 91 were included in the final data analysis. Subjects in the video tool group demonstrated significantly higher recall of key aspects of informed consent and higher satisfaction with the informed consent process versus the traditional consent group. The history of prior colonoscopy was similar between both groups. Mean endoscopy operation metrics were not negatively impacted by the inclusion of the video tool. CONCLUSION: Patients undergoing screening and diagnostic colonoscopies who received informed consent supplemented by a video tool had a higher recall of core aspects of informed consent and higher satisfaction with the process, with no impact on procedural times.

A Rare Case of Takotsubo Cardiomyopathy-Induced Acute Liver Failure

Hypoxic hepatitis is a common cause of abnormal liver biochemistries in hospitalized patients. It is important clinicians maintain a high index of suspicion for diagnosis so that appropriate supportive therapies may be implemented in a timely manner. We present a rare case of takotsubo cardiomyopathy-induced hypoxic hepatitis and resultant acute liver failure in a patient after an intentional drug overdose. Once competing etiologies of acute liver failure were excluded and the diagnosis of hypoxic hepatitis was established, therapy was focused on the patient's cardiomyopathy in an effort to simultaneously improve her liver function.

Correction to: Takotsubo Cardiomyopathy Causing Induced Acute Liver Failure.

[This corrects the article DOI: 10.14309/crj.0000000000000413.].

CMV coinfection in treatment refractory immune checkpoint inhibitor colitis.

As immune checkpoint inhibitors (ICIs) are increasingly used, clinicians are more frequently encountering the side effects of these therapies. ICIs have been implicated in numerous adverse effects against healthy tissues. We present a case of a patient who developed treatment refractory checkpoint inhibitor colitis. Following colonoscopy, it was discovered that this patient had cytomegalovirus (CMV) coinfection. This case report highlights the importance of undertaking an appropriate assessment, including endoscopic and histologic investigation, of patients with presumed ICI colitis. Accurately diagnosing a superimposed CMV colitis changes clinical management and can improve patient outcomes.

Students as catalysts for curricular innovation: A change management framework.

Introduction: The role of medical students in catalyzing and leading curricular change in US medical schools is not well described. Here, American Medical Association student and physician leaders in the Accelerating Change in Medical Education initiative use qualitative methods to better define student leadership in curricular change.Methods: The authors developed case studies describing student leadership in curricular change efforts. Case studies were presented at a national medical education workshop; participants provided worksheet reflections and were surveyed, and responses were transcribed. Kotter's change management framework was used to categorize reported student roles in curricular change. Thematic analysis was used to identify barriers to student engagement and activators to overcome these barriers.Results: Student roles spanned all eight steps of Kotter's change management framework. Barriers to student engagement were related to faculty (e.g. view student roles narrowly), students (e.g. fear change or expect faculty-led curricula), or both (e.g. lack leadership training). Activators were: (1) recruiting collaborative faculty, staff, and students; (2) broadening student leadership roles; (3) empowering student leaders; and (4) recognizing student successes.Conclusions: By applying these activators, medical schools can build robust student-faculty partnerships that maximize collaboration, moving students beyond passive educational consumption to change agency and curricular co-creation.

A Single-Institution Analysis of 126 Patients Treated with Stereotactic Radiosurgery for Brain Metastases.

BACKGROUND: The objective of this study was to report our institutional experience with Gamma Knife® Radiosurgery (GKRS) in the treatment of patients with brain metastases. METHODS: Retrospectively collected demographic and clinical data on 126 patients with intracranial metastases were reviewed. The patients in our study underwent GKRS at Vidant Medical Center between 2009 and 2014. Kaplan-Meier curves were used to compare survival based on clinical characteristics for univariate analysis, and a Cox proportional hazards model was used for multivariate analysis. RESULTS: The median age of the patient population was 62 years. Medicare patients constituted 51% of our patient cohort and Medicaid patients 15%. The most common tumor histologies were non-small cell lung cancer (50%), breast cancer (12.7%), and melanoma (11.9%). The median overall survival time for all patients was 5.8 months. Patients with breast cancer had the longest median survival time of 9.15 months, while patients with melanoma had the shortest median survival time of 2.86 months. On univariate analysis, the following factors were predictors for improved overall survival, ECOG score 0 or 1 vs. 2 or greater (17.0 vs. 1.8 months, p < 0.001), controlled extracranial disease vs. progressive extracranial disease (17.4 vs. 4.6 months, p = 0.0001), recursive partitioning analysis Stage I vs. II-III (18.2 vs. 6.2 months, p < 0.007), multiple GKRS treatments (p = 0.002), prior brain metastasectomy (p = 0.012), and prior chemotherapy (p = 0.021). Age, ethnicity, gender, previous external beam radiation therapy, number of brain metastases, and hemorrhagic vs. non-hemorrhagic tumors were not predictors of longer median survival time. Number of metastatic brain lesions of 1-3 vs. ≥4 (p = 0.051) and insurance status of Medicare/Medicaid vs. commercial insurance approached significance (13.7 vs. 6.8 months, p = 0.08). On multivariate analysis, ECOG performance status 0-1 (p < 0.001), multiple GKRS treatments (p = 0.003), and control of extracranial disease (p = 0.001) remained significant predictors of survival. CONCLUSION: ECOG score, control of extracranial disease, and multiple GKRS treatments are predictors of longer median survival following GKRS in our patient population. GKRS is an effective treatment for brain metastases, but these factors may be considered in patient selection for GKRS.

Determination of intracellular unbound concentrations and subcellular localization of drugs in rat sandwich-cultured hepatocytes compared with liver tissue.

Prediction of clinical efficacy, toxicity, and drug-drug interactions may be improved by accounting for the intracellular unbound drug concentration (C(unbound)) in vitro and in vivo. Furthermore, subcellular drug distribution may aid in predicting efficacy, toxicity, and risk assessment. The present study was designed to quantify the intracellular C(unbound) and subcellular localization of drugs in rat sandwich-cultured hepatocytes (SCH) compared with rat isolated perfused liver (IPL) tissue. Probe drugs with distinct mechanisms of hepatocellular uptake and accumulation were selected for investigation. Following drug treatment, SCH and IPL tissues were homogenized and fractionated by differential centrifugation to enrich for subcellular compartments. Binding in crude lysate and cytosol was determined by equilibrium dialysis; the C(unbound) and intracellular-to-extracellular C(unbound) ratio (K(pu,u)) were used to describe accumulation of unbound drug. Total accumulation (K(pobserved)) in whole tissue was well predicted by the SCH model (within 2- to 3-fold) for the selected drugs. Ritonavir (K(pu,u) ∼1) was evenly distributed among cellular compartments, but highly bound, which explained the observed accumulation within liver tissue. Rosuvastatin was recovered primarily in the cytosolic fraction, but did not exhibit extensive binding, resulting in a K(pu,u) >1 in liver tissue and SCH, consistent with efficient hepatic uptake. Despite extensive binding and sequestration of furamidine within liver tissue, a significant portion of cellular accumulation was attributed to unbound drug (K(pu,u) >16), as expected for a charged, hepatically derived metabolite. Data demonstrate the utility of SCH to predict quantitatively total tissue accumulation and elucidate mechanisms of hepatocellular drug accumulation such as active uptake versus binding/sequestration.