Association between ezetimibe usage and hepatitis C RNA levels in uninfected kidney transplant recipients who received hepatitis C infected kidneys.

Kidney transplantation (KT) from hepatitis C virus infected (HCV+) donors to HCV negative recipients achieve excellent graft function but have relatively higher rates of post-KT co-infections presumably due to prolonged HCV viremia in transmission-and-treat approach. Ezetimibe acts as an antagonist of Niemann-Pick C1-Like 1 receptor required for HCV entry and theoretically can reduce HCV viremia. However, no data is available to examine the role of ezetimibe as a bridge therapy between KT surgery and direct acting antiviral (DAA) initiation. A retrospective cohort study including 70 HCV+ to HCV negative KT recipients from Methodist University Hospital and Vanderbilt University Medical Center was performed to determine the association between ezetimibe usage and HCV viremia. Twenty patients received ezetimibe daily while 50 patients did not. Primary outcome of study was mean HCV RNA level at 1-2 weeks post-KT and before initiation of DAA. Median (IQR) viral load (VL) in log copies/ml was one log lower in ezetimibe group versus non-ezetimibe group (4.1 [3.7-5.3] vs. 5.1 [4.4-5.5], P = .01), and highest VL was also lower in ezetimibe group (4.2 [3.7-5.4] vs. 5.4 [4.7-5.9], P = .006). We concluded that ezetimibe bridge therapy might be associated with reduction in HCV VL while waiting for DAA initiation in HCV+ to HCV negative KT recipients.

Safety of Baricitinib 4 mg for the Treatment of Moderate to Severe Rheumatoid Arthritis.

OBJECTIVE: We evaluated the safety of baricitinib 4 mg at 24 weeks for the treatment of moderate to severe rheumatoid arthritis (RA). METHODS: Multiple databases were searched from inception up to November 26, 2019 for randomized controlled trials comparing baricitinib 4 mg with placebo for the treatment of moderate to severe RA. The safety outcomes of interest were the incidence of serious adverse events, adverse events leading to study discontinuation, all infections, and serious infections. Adjusted risk ratios (RRs) with 95% confidence intervals (CIs) were pooled for safety outcomes. The Cochrane tool was used to assess the risk of bias. RESULTS: This analysis included four randomized controlled trials with 3106 patients. For serious adverse events, the pooled RR (95% CI) was 1.09 (0.76-1.57). For adverse events leading to study discontinuation, the pooled RR (95% CI) was 1.41 (0.94-2.11). For all reported infections, the pooled RR (95% CI) was 1.24 (1.10-1.40), For serious infections, pooled RR (95% CI) was 0.97 (0.51-2.57). CONCLUSIONS: Patients with RA taking 4 mg baricitinib daily did have an increased risk of infections; however, the incidence of serious adverse events, adverse events leading to study discontinuation, or serious infections were not significantly different in patients treated with baricitinib 4 mg compared with placebo.

Association of Pretransplant Renal Function With Liver Graft and Patient Survival After Liver Transplantation in Patients With Nonalcoholic Steatohepatitis.

Nonalcoholic steatohepatitis (NASH) is one of the top 3 indications for liver transplantation (LT) in Western countries. It is unknown whether renal dysfunction at the time of LT has any effect on post-LT outcomes in recipients with NASH. From the United Network for Organ Sharing-Standard Transplant Analysis and Research data set, we identified 4088 NASH recipients who received deceased donor LT. We divided our recipients a priori into 3 categories: group 1 with estimated glomerular filtration rate (eGFR) <30 mL/minute/1.73 m2 at the time of LT and/or received dialysis within 2 weeks preceding LT (n = 937); group 2 with recipients who had eGFR ≥30 mL/minute/1.73 m2 and who did not receive renal replacement therapy prior to LT (n = 2812); and group 3 with recipients who underwent simultaneous liver-kidney transplantation (n = 339). We examined the association of pretransplant renal dysfunction with death with a functioning graft, all-cause mortality, and graft loss using competing risk regression and Cox proportional hazards models. The mean ± standard deviation age of the cohort at baseline was 58 ± 8 years, 55% were male, 80% were Caucasian, and average exception Model for End-Stage Liver Disease score was 24 ± 9. The median follow-up period was 5 years (median, 1816 days; interquartile range, 1090-2723 days). Compared with group 1 recipients, group 2 recipients had 19% reduced trend for risk for death with a functioning graft (subhazard ratio [SHR], 0.81; 95% confidence interval [CI], 0.64-1.02) and similar risk for graft loss (SHR, 1.25; 95% CI, 0.59-2.62), whereas group 3 recipients had similar risk for death with a functioning graft (SHR, 1.23; 95% CI, 0.96-1.57) and graft loss (SHR, 0.18; 95% CI, 0.02-1.37) using an adjusted competing risk regression model. In conclusion, recipients with preserved renal function before LT showed a trend toward lower risk of death with a functioning graft compared with SLKT recipients and those with pretransplant severe renal dysfunction in patients with NASH.

Achieving Sustained Virological Response in Liver Transplant Recipients With Hepatitis C Decreases Risk of Decline in Renal Function.

The effect of antiviral therapy (AVT) on kidney function in liver transplantation (LT) recipients has not been well described despite known association of hepatitis C virus (HCV) infection with chronic kidney disease (CKD). We compared the incidence of CKD and end-stage renal disease (ESRD) in 204 LT recipients with HCV based on treatment response to AVT. The mean estimated glomerular filtration rate (eGFR) at baseline (3 months after LT) was similar in the sustained virological response (SVR; n = 145) and non-SVR group (n = 59; 69 ± 21 versus 65 ± 33 mL/minute/1.73 m2 ; P = 0.27). In the unadjusted Cox proportional regression analysis, the presence of SVR was associated with an 88% lower risk of CKD (hazard ratio, 0.12; 95% confidence interval [CI], 0.05-0.31) and 86% lower risk of ESRD (odds ratio, 0.14; 95% CI, 0.05-0.35). Similar results were found after adjusting for propensity score and time-dependent Cox regression analyses. The estimated slopes of eGFR based on a 2-stage mixed model of eGFR were calculated. Patients with SVR had a less steep slope in eGFR (-0.60 mL/minute/1.73 m2 /year; 95% CI, -1.50 to 0.30; P = 0.190) than recipients without SVR (-2.53 mL/minute/1.73 m2 /year; 95% CI, -3.99 to -1.07; P = 0.001), and the differences in the slopes were statistically significant (P = 0.026). In conclusion, in LT recipients with chronic HCV infection, achieving SVR significantly lowers the risk of decline in renal function and progression to ESRD independent of the AVT therapy used.

History of psychosis and mania, and outcomes after kidney transplantation - a retrospective study.

History of psychosis or mania, if uncontrolled, both represent relative contraindications for kidney transplantation. We examined 3680 US veterans who underwent kidney transplantation. The diagnosis of history of psychosis/mania was based on a validated algorithm. Measured confounders were used to create a propensity score-matched cohort (n = 442). Associations between pretransplantation psychosis/mania and death with functioning graft, all-cause death, graft loss, and rejection were examined in survival models and logistic regression models. Post-transplant medication nonadherence was assessed using proportion of days covered (PDC) for tacrolimus and mycophenolic acid in both groups. The mean ± SD age of the cohort at baseline was 61 ± 11 years, 92% were male, and 66% and 27% of patients were white and African-American, respectively. Compared to patients without history of psychosis/mania, patients with a history of psychosis/mania had similar risk of death with functioning graft [subhazard ratio (SHR) (95% confidence interval (CI)): 0.94(0.42-2.09)], all-cause death [hazard ratio (95% CI): 1.04 (0.51-2.14)], graft loss [SHR (95% CI): 1.07 (0.45-2.57)], and rejection [odds ratio(95% CI): 1.23(0.60-2.53)]. Moreover, there was no difference in immunosuppressive drug PDC in patients with and without history of psychosis/mania (PDC: 76 ± 21% vs. 78 ± 19%, P = 0.529 for tacrolimus; PDC: 78 ± 17% vs. 79 ± 18%, P = 0.666 for mycophenolic acid). After careful selection, pretransplantation psychosis/mania is not associated with adverse outcomes in kidney transplant recipients.

Quadricuspid aortic valve infective endocarditis.

Infective endocarditis complicating a quadricuspid aortic valve (QAV) is rare. Previous reports highlight the increased risk for complications, including progressive aortic regurgitation, decompensated heart failure, and valve perforation. Thus, cardiologists must be able to quickly identify QAVs to guide rapid evaluation and treatment. We report a case of infective endocarditis in a QAV identified on echocardiography and effectively managed with medical therapy alone without complications over an 8-year follow-up period. © 2017 Wiley Periodicals, Inc. J Clin Ultrasound 46:145-148, 2018.

Pre-ESRD Dementia and Post-ESRD Mortality in a Large Cohort of Incident Dialysis Patients.

BACKGROUND: Conservative management may be a desirable option for elderly, fragile, or demented patients who reach end-stage renal disease (ESRD), yet some patients with dementia are placed on renal replacement therapy nonetheless. METHODS: From a nationwide cohort of 45,076 US veterans who transitioned to ESRD over 4 contemporary years (October 1, 2007 to September 30, 2011), we identified 1,336 (3.0%) patients with International Classification of Diseases, Ninth Revision, Clinical Modification code-based dementia diagnosis during the prelude (predialysis) period. We examined the association of prelude dementia with all-cause mortality within the first 6 months following transition to dialysis, using a propensity-matched cohort and Cox proportional hazards models. RESULTS: In the entire cohort, the overall mean ± standard deviation age at baseline was 72 ± 11 years, 95% were male, 23% were African-American, and 66% were diabetic. There were 8,080 (18.5%) deaths (mortality rate, 412; 95% confidence interval [CI], 403-421/1,000 patient-years) in the dementia-negative group, and 396 (29.6%) deaths (mortality rate, 708; 95% CI, 642-782/1,000 patient-years) in the dementia-positive group in the entire cohort in the first 6 months after dialysis initiation. Presence of dementia was associated with higher risk of all-cause mortality (adjusted hazard ratio, 1.25; 95% CI, 1.12-1.38) compared to dementia-free patients in the first 6 months after dialysis initiation. CONCLUSION: Pre-ESRD dementia is associated with increased risk of early post-ESRD mortality in veterans transitioning to dialysis.

Bilateral nonpitting edema and xerotic skin.

When treatment for cellulitis and a suspected exacerbation of congestive heart failure failed, we ordered a biopsy. The pathology report made the diagnosis clear.

Hold the Gaba: A Case of Gabapentin-induced Hepatotoxicity.

A drug-induced liver injury is one of the most common causes of acute liver failure. While acetaminophen is the most common etiology, other offending medications include amoxicillin-clavulanic acid, amiodarone, isoniazid, and fluoroquinolones to name a few. Gabapentin, a gamma-aminobutyric acid (GABA) analogue, has infrequently been reported to cause liver injury; however, the causality in the previous reports is contested. Herein, we report a gabapentin-induced hepatocellular injury in a patient without another identifiable cause for acute liver injury. Discontinuing gabapentin resulted in rapid reversal improvement in hepatocellular injury.

Do we really need more evidence to use hepatitis C positive donor kidney more liberally?

The number of patients listed active for kidney transplantation has continued to rise over the last 10 years, leading to significantly increased wait-list time for patients awaiting kidney transplantation in the USA. This increased demand has led to a supply-demand mismatch and should prompt clinicians to seek timely solutions to improve access to available organs. Hepatitis C virus positive [HCV(+)] kidneys continue to be discarded without clear evidence that they lead to poor outcomes in the current era of highly efficacious HCV treatment with direct-acting antiviral agents (DAAs). Increased utilization of HCV(+) donor kidneys will decrease wait-list time and improve availability of donor organs. Emerging data suggests that HCV can be successfully treated with DAAs after kidney transplantation with 100% sustained virologic response rates and no significant changes from baseline kidney function. Utilization of HCV(+) donor kidneys should be considered more liberally in the era of highly effective HCV treatment. Further studies are warranted to assess the long-term effect of HCV(+) donor kidneys in transplant recipients in the new era of DAAs.

Therapeutic plasmapheresis for hypertriglyceridemia-associated acute pancreatitis: case series and review of the literature.

BACKGROUND: Severe hypertriglyceridemia (HTG) is the third leading cause of acute pancreatitis (AP) in the United States. The current standard of care includes management of HTG using pharmacological therapy. More recently, plasmapheresis has been proposed as a therapeutic tool for decreasing triglyceride (TG) levels, especially in critically ill patients. Few studies are available to ascertain overall benefits of plasmapheresis over traditional management. OBJECTIVE: To analyze the outcomes of patients treated with plasmapheresis for severe HTG-associated pancreatitis. METHODS: We conducted a retrospective chart review of three patients with severe HTG- associated (TGs greater than 1000 mg/dl; 11.29 mmol/l) AP at the Methodist University Hospital. All the patients underwent plasmapheresis as part of their treatment. RESULTS: The average TG level before plasmapheresis was 3532 mg/dl (range: 2524-4562 mg/dl; 39.9 mmol/l; range: 28.5-51.6 mmol/l). All patients made a full recovery, with a significant improvement in TG levels after plasmapheresis. The mean number of sessions was 1.3 (range 1-2), and mean TG level after plasmapheresis was 1051 mg/dl (range: 509-1771 mg/dl; 11.9 mmol/l; range: 5.8-20 mmol/l). After the first session, the average reduction of TG level was 2481 mg/dl (range 753-3750 mg/dl; 28 mmol/l; range: 8.5-42.4 mmol/l) or approximately 70%. None of the patients developed complications related to plasmapheresis. CONCLUSIONS: Plasmapheresis can be an effective and rapid treatment option in patients with severe HTG and complications. However, further research, including randomized controlled studies, is necessary.

Disseminated Nocardia Farcinica Pneumonia with Left Adrenal Gland Abscess.

Adrenal masses pose a diagnostic challenge. The differential diagnosis includes functional adrenal tumors, incidentally found adrenal masses, metastases from an unknown primary cancer, and abscesses. Infrequently, adrenal gland abscesses have been reported in disseminated nocardiosis affecting immunocompetent and immunocompromised patients. We report a case of disseminated Nocardia farcinica pneumonia with an adrenal gland abscess in an immunocompetent patient with no identified risk factors for nocardiosis.

Metastatic Squamous Cell Carcinoma of the Pleura: A Rare Complication of Hidradenitis Suppurativa.

BACKGROUND Squamous cell carcinoma (SCC), also known as Marjolin ulcer, is a rare complication of hidradenitis suppurativa (HS). Metastatic SCC from HS typically involves the axial skeleton or abdominopelvic viscera. Metastatic disease to the lungs is a rare phenomenon with only three reported cases of lung parenchyma. We present a biopsy proven case of metastatic SCC to the pleura from gluteal HS. CASE REPORT A 46-year-old male with a history of recently diagnosed Marjolin ulcer secondary to gluteal HS was transferred to our intensive care unit for acute hypoxemic respiratory failure secondary to recurrent pleural effusion. On examination, patient was febrile (38.3 °C), normotensive (blood pressure 98/65 mm Hg), tachycardic (116 beats/minute) and tachypneic (40 breaths/minute) with oxygen saturation of 93% on room air. He was in moderate distress requiring endotracheal intubation and mechanical ventilation. Chest examination revealed decreased breath sounds bilaterally and skin examination was significant for 18 cm wide sacral lesion. CT thorax showed bilateral pleural effusions, pleural thickening, and scattered nodular densities within both lungs concerning for metastatic disease. Thoracentesis showed lymphocyte predominant exudate with negative cytology for malignant cells. A video-assisted thoracoscopic surgery (VATS) illustrated thickened pleural rind with histopathology and positive p40 stain consistent with invasive well-to-moderately differentiated keratinizing SCC.  CONCLUSIONS SCC arising from HS is rare and metastatic disease to the pleura has not been reported previously. Strong clinical suspicion for malignancy is warranted in patients with advanced HS and evolving pulmonary symptoms despite negative cytology.