ObjectiveGenome-wide association studies have uncovered a large number of genetic variants associated with type 2 diabetes or related phenotypes. In many cases the causal gene or polymorphism has not been identified, and its impact on response to anti-hyperglycemic medications is unknown. The Study to Understand the Genetics of the Acute Response to Metformin and Glipizide in Humans (SUGAR-MGH, NCT01762046) is a novel resource of genetic and biochemical data following glipizide and metformin administration. We describe recruitment, enrollment, and phenotyping procedures and preliminary results for the first 668 of our planned 1,000 participants enriched for individuals at risk of requiring anti-diabetic therapy in the future.MethodsAll individuals are challenged with 5 mg glipizide × 1; twice daily 500 mg metformin × 2 days; and 75-g oral glucose tolerance test following metformin. Genetic variants associated with glycemic traits and blood glucose, insulin, and other hormones at baseline and following each intervention are measured.ResultsApproximately 50% of the cohort is female and 30% belong to an ethnic minority group. Following glipizide administration, peak insulin occurred at 60 minutes and trough glucose at 120 minutes. Thirty percent of participants experienced non-severe symptomatic hypoglycemia and required rescue with oral glucose. Following metformin administration, fasting glucose and insulin were reduced. Common genetic variants were associated with fasting glucose levels.ConclusionsSUGAR-MGH represents a viable pharmacogenetic resource which, when completed, will serve to characterize genetic influences on pharmacological perturbations, and help establish the functional relevance of newly discovered genetic loci to therapy of type 2 diabetes.Trial RegistrationClinicalTrials.gov NCT01762046
Chronic liver disease has been associated with pulmonary dysfunction both before and after liver transplantation. Post-liver transplantation pulmonary complications can affect both morbidity and mortality often necessitating intensive care during the immediate postoperative period. The major pulmonary complications include pneumonia, pleural effusions, pulmonary edema, and atelectasis. Poor clinical outcomes have been known to be associated with age, severity of liver dysfunction, and preexisting lung disease as well as perioperative events related to fluid balance, particularly transfusion and fluid volumes. Delineating each and every one of these pulmonary complications and their associated risk factors becomes paramount in guiding specific therapeutic strategies.
Kratom is an herbal supplement used to relieve chronic pain or opioid withdrawal symptoms. Recent news articles covering adverse effects associated with kratom use have brought attention to its organ toxicities. Reports of kratom-induced hepatic toxicity are limited and only three case reports of kratom-induced liver injury with histopathologic examination of the liver biopsies are available. A 40-year-old female presented with symptoms of mixed cholestatic and hepatocellular liver injury without clear etiology. The laboratory and imaging workup suggested possibilities of autoimmune hepatitis, autoimmune hepatitis-primary biliary cholangitis (PBC) overlap syndrome, or drug-induced liver injury. Autoantibodies including anti-mitochondrial antibody (AMA) were negative. Liver biopsy showed granulomatous hepatitis with prominent duct injury, suggestive of AMA-negative PBC. She subsequently was referred to a hepatologist and a history of recent kratom use was finally revealed. Kratom was discontinued and the symptoms improved. Kratom-induced hepatic toxicity may manifest with variable biochemical and clinical abnormalities. Histologically, it may mimic AMA-negative PBC. Our case highlights the importance of thorough history taking, interdisciplinary approach and communication for optimal patient care.
Introduction: This was a single-center retrospective study to evaluate incidence, prognosis, and risk factors in patients with postoperative pleural effusions, a common pulmonary complication following liver transplantation. Methods: A retrospective review was performed on 374 liver transplantation cases through a database within the timeframe of January 1, 2009 through December 31, 2015. Demographics, pulmonary and cardiac function testing, laboratory studies, intraoperative transfusion/infusion volumes, postoperative management, and outcomes were analyzed. Results: In the immediate postoperative period, 189 (50.5%) developed pleural effusions following liver transplantation of which 145 (76.7%) resolved within 3 months. Those who developed pleural effusions demonstrated a lower fibrinogen (149.6 ± 66.3 mg/dL vs 178.4 ± 87.3 mg/dL; P = .009), total protein (5.8 ± 1.0 mg/dL vs 6.1 ± 1.2 mg/dL; P = .04), and hemoglobin (9.8 ± 1.8 mg/dL vs 10.3 ± 1.9 mg/dL; P = .004). There was not a statistically significant difference in 1-year all-cause mortality and in-hospital mortality between liver transplant recipients with and without pleural effusions. Liver transplant recipients who developed pleural effusions had a longer hospital length of stay (16.4 ± 10.9 days vs 14.0 ± 16.5 days; P = .1), but the differences were not statistically significant. However, there was a significant difference in tracheostomy rates (11.6% vs 5.4%; P = .03) in recipients who developed pleural effusions compared to recipients who did not. Conclusions: In summary, pleural effusions are common after liver transplantation and are associated with increased morbidity. Pre- and intraoperative risk factors can offer both predictive and prognostic value for post-transplantation pleural effusions. Further prospective studies will be needed to further evaluate the relevance of these findings to limit instances of postoperative pleural effusions.
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