Effect of Add-On Therapy of Sodium-Glucose Cotransporter 2 Inhibitors and Dipeptidyl Peptidase 4 Inhibitors on Adipokines in Type 2 Diabetes Mellitus.

BACKGROUND: Excess adiposity is associated with an increased risk of cardiovascular disease due to metabolic changes in the body. Visceral obesity increases the risk of diabetes mellitus through adipocytokines and hence the effective targeting therapies are essential to control obesity in high-risk individuals. The study's main objective was to evaluate the effect of add-on therapy of sodium-glucose cotransporter 2 (SGLT2) inhibitors and dipeptidyl peptidase 4 (DPP4) inhibitors on visceral fat-associated serum adipokines. METHODS: The study included 90 subjects diagnosed with type 2 diabetes mellitus. The blood samples were taken before starting first-line therapy with metformin, 12 weeks after starting metformin therapy and 12 weeks after starting add-on therapy. Serum adipokines were analyzed with enzyme-linked immunosorbent assay (ELISA). Hemoglobin A1c (HbA1c) level was estimated with high-performance liquid chromatography (HPLC). The biochemical variables were measured using Cobas® 6000 analyzer. RESULTS: The mean adiponectin level was significantly elevated with add-on therapy using SGLT2 inhibitors and DPP4 inhibitors (P < 0.001). The mean retinol binding protein 4 (RBP4), fatty acid binding protein 4 (FABP4) and visfatin levels were reduced considerably (P < 0.001). The SGLT2 inhibitors are more effective on serum FABP4 in patients with type 2 diabetes (P = 0.038). The mean fasting plasma glucose (FPG), postprandial blood glucose (PPBG) and HbA1c levels were reduced significantly with add-on therapy (P < 0.001). Lipid profile was also altered significantly with this add-on therapy (P < 0.001). CONCLUSIONS: The results indicate that add-on therapy exerts a beneficial effect in type 2 diabetic patients insufficiently controlled with metformin only by altering the visceral fat-associated adipokine levels and controlling the metabolic activities.

Early liver transplantation after COVID-19 infection: The first report.

COVID-19 (coronavirus disease 2019) has impacted solid organ transplantation (SOT) in many ways. Transplant centers have initiated SOT despite the COVID-19 pandemic. Although it is suggested to wait for 4 weeks after COVID-19 infection, there are no data to support or refute the timing of liver transplant after COVID-19 infection. Here we describe the course and outcomes of COVID-19-infected candidates and healthy living liver donors who underwent transplantation. A total of 38 candidates and 33 potential living donors were evaluated from May 20, 2020 until October 30, 2020. Ten candidates and five donors were reverse transcriptase-polymerase chain reaction (RT-PCR) positive for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pretransplant. Four candidates succumbed preoperatively. Given the worsening of liver disease, four candidates underwent liver transplant after 2 weeks due to the worsening of liver disease and the other two candidates after 4 weeks. Only one recipient died due to sepsis posttransplant. Three donors underwent successful liver donation surgery after 4 weeks of COVID-19 infection without any postoperative complications, and the other two were delisted (as the candidates expired). This report is the first to demonstrate the feasibility of elective liver transplant early after COVID-19 infection.

Rapid Reversal of Liver Steatosis With Life Style Modification in Highly Motivated Liver Donors.

BACKGROUND: Liver steatosis is the leading cause of donor rejection in living donor liver transplantation. Rapid weight loss is difficult to achieve in a short period of time, moreover it has been thought to worsen liver histology. METHODS: Donors who had significant steatosis based on liver biopsy were recommended 1200 Kcal/day and a minimum of 60 min/day moderate cardio training. Two patients were advised statins for dyslipidemia. None of the donors had metabolic syndrome. A second ultrasound guided liver biopsy was done at 28 ± 10 days. Donors with nonalcoholic steatohepatitis/fibrosis or >30% steatosis were not included. RESULTS: From July 2010 to January 2015, 16 donors were advised aggressive life style modification after initial biopsy; 15 (10 males, age 27.5 ± 6.5 years, baseline body mass index 28.4 ± 2.1 Kg/M(2)) successfully reduced weight and 14 underwent donation after favorable second biopsy. Mean weight loss was 7 ± 4.3 kg (8.4 ± 4.6%). Second liver biopsy was done at 28 ± 10 days, there was decrease in steatosis in all but one including normalization of liver biopsy in 7 donors. Three donors had mild inflammation on first biopsy and they had improvement in second biopsy. All the donors and their recipients had an uneventful post-operative course. CONCLUSION: Steatosis can be reversed in a short duration by aggressive life style modifications in highly motivated liver donors.

Sarcopenic obesity with metabolic syndrome: a newly recognized entity following living donor liver transplantation.

OBJECTIVE: There are limited data about sarcopenic obesity in liver transplant recipients. METHODS: Living donor liver transplant recipients with at least 12 months of follow-up were included. Metabolic syndrome (MS) was defined as ≥ 3 ATP III criteria. Body composition was assessed by bioelectrical impedance. Immunosuppression protocol included short-term steroids, mycophenolate and calcineurin inhibitors (mainly tacrolimus). Data are shown as percentage, mean ± SD, or median (25-75 IQR). RESULTS: The study comprised 82 patients (males 69), aged 50.5 ± 10.65 yr, and follow-up 24 (12-38.5) months. Etiology for cirrhosis was alcohol 29%, hepatitis C 22%, hepatitis B 17%, cryptogenic 24%, and others 7%. Post-transplant sarcopenic obesity was present in 72 (88%), and MS was present in 43 (52%) of recipients with no significant difference among etiologies. There were significant differences between pre- and post-transplant body mass index, triglycerides, high-density lipoprotein, low-density lipoprotein (p = 0.000 for all), prevalence of hypertension (18% vs. 39%), and diabetes (20% vs. 56%). Patients with sarcopenic obesity had significantly higher body mass index, waist circumference, and MS (57% vs. 20%, p = 0.041) when compared to patients without sarcopenic obesity. CONCLUSION: Despite resuming routine activities, the majority of liver transplant recipients develop sarcopenic obesity and MS. The importance and role of appropriate nutrition and exercise after transplantation merits further investigation.

Excellent outcome of living donor liver transplantation in patients with hepatopulmonary syndrome: a single centre experience.

INTRODUCTION: Hepatopulmonary syndrome (HPS) worsens the prognosis of cirrhosis and liver transplantation is only definitive treatment. There is paucity of data about role of living donor liver transplantation (LDLT) in HPS. METHODS: Fourteen patients with HPS and cirrhosis who underwent LDLT were prospectively included. HPS was defined as PaO2 < 80 mmHg in presence of demonstrable macro-aggregated albumin (MAA) scan shunt fraction >6%. RESULTS: The study group composed of 11 male and three female patients, mean age 50.3 ± 8.6 yr. Most common presentations were dyspnea (92.8%), cyanosis (78.5%) and clubbing (64.2%). Mean model for end-stage liver disease (MELD) score was 18.2 ± 4.7, mean MAA shunt fraction was 23.0 ± 13.2%, mean PaO2 was 58.7 ± 8.4 mmHg. Two patients had very severe HPS (PaO2 <50 mmHg), five had severe HPS (PaO2 >50 <60 mmHg) and seven had moderate HPS (PaO2 >60 <80 mmHg). All patients underwent right lobe LDLT. The overall time to extubation was 2 (1-32 days) and for hospital stay was 20 (17-46 days). The main complications in post-LT course were infection in 57% (cytomegalovirus or bacterial). All the patients are alive and off oxygen at a mean follow up of 29 ± 25 months. CONCLUSION: We report one of the largest series of LDLT in HPS which has shown excellent results.

A case of carcinoma rete testis: histomorphological, immunohistochemical and ultrastructural findings and review of literature.

A 72-year-old man presenting with a secondary hydrocoel underwent orchidectomy. Gross examination revealed a tumor arising in the region of the rete testis, which on histopathology proved to be a papillary adenocarcinoma. The patient did not have evidence of any other neoplasia elsewhere in the body. The lesion fulfilled the anatomic criteria elucidated by Nochomovitz et al to be labelled as adenocarcinoma of Rete testis. Electron microscopy revealed characteristic nuclear infoldings and microtubules with two different arrangements. The tubules were either seen to form concentric circles or were in irregular groups with filaments interspersed. The lesion on immunohistochemistry was negative for germ cell markers AFP and HCG, and was positive for cytokeratin and epithelial membrane antigen. A review of literature is also presented.