Purpose: EBV-positive smooth muscle tumor (EBV+SMT) is a rare disease with no established therapy. We describe the largest single institution analysis in renal transplant recipients. It aims to define its clinical features and determine the expression of EBV latent genes as well as key molecular pathways. Experimental Design: Patients with EBV+SMT were identified from the Singapore General Hospital Renal Transplant Registry database. These tumors were investigated for expression of EBV latent genes with Southern blots, EBV latent antigens, mammalian target of rapamycin (mTOR), Akt, p70 S6 kinase, and vascular endothelial growth factor using immunohistochemistry, as well as methylation status of cancer-related genes using methylation-specific PCR. Results: Eight were found to be EBV+SMT in 1,123 transplant patients. All displayed indolent clinical courses and were unresponsive to immunosuppression reduction. Complete tumor regression was seen in one patient following administration of sirolimus. These tumors display the full range of known EBV latent genes. Immunohistochemistry with total and phosphorylated mTOR and Akt were positive for all patients, and vascular endothelial growth factor was positive in 25% of patients, suggesting activation of the mTOR/Akt pathway. Methylation of RASSF1A was found in all tissue samples, whereas promoter hypermethylation of RARβ, GSTP1, DAPK, and p14 was observed in some samples. Conclusions: Our results suggest that these tumors display a EBV type III latency pattern. The mTOR pathway is also activated. EBV may play a role in silencing RASSF1A. EBV-specific immunotherapy, mTOR inhibitors, and demethylating agents are possible therapeutic options in this disease. (Clin Cancer Res 2009;15(17):5350-8)
Surgical resection in combination with decreasing immunosuppression or conversion to sirolimus appears to be effective in the treatment of EBV SMT in KTR.
Creating a vascular access in the presence of a cardiovascular implantable electronic device (CIED) in a patient with or approaching end-stage renal disease can be challenging. In this study, we aimed to evaluate the impact of a CIED on the outcomes of vascular access creation in hemodialysis patients and determine their effects on vascular access patency. This is a single-center retrospective review of hemodialysis patients who underwent vascular access creation after CIED placement. Outcomes of vascular access creation and need for endovascular interventions were compared between patients with vascular access created ipsilateral and contralateral to the site of CIED. Comparing patients with arteriovenous (AV) access created ipsilateral to CIED placement (n=19) versus the contralateral side (n=17), the primary failure rate was 78.9% versus 35.3% (p=0.02). For AV accesses that were matured, the median primary patency durations for AV accesses created ipsilateral to the CIED was 11.2 months compared to 7.8 months for AV accesses created contralateral to the CIED (p=1.00). AV accesses created ipsilateral to a CIED have a higher primary failure rate compared with the contralateral arm and should be avoided as much as possible.
BackgroundWarfarin related nephropathy is one of the potential complications of warfarin therapy. Despite the well described histological entity, the clinical course and approach to warfarin related nephropathy in patients requiring life-long anticoagulation is however not well described in the literature.Case presentationWe report the clinical course of a 56 years old Chinese lady who presented with over anti-coagulation and acute kidney injury while on warfarin therapy for permanent atrial fibrillation and mechanical valve replacement. Renal biopsy was performed as the acute kidney injury was persistent despite normalization of the International Normalized Ratio and the diagnosis of warfarin related nephropathy was made. Temporary interruption of anti-coagulation, in combination with oral N-acetylcysteine resulted in subsequent stabilization of renal function.ConclusionThe diagnosis of warfarin induced nephropathy should be considered in patients presenting with unexplained acute kidney injury and over anti-coagulation. Awareness of this clinical entity is important for clinician managing anti-coagulation therapy and renal function should be monitored regularly in patients who are on warfarin therapy.
With the exponential surge in patients with coronavirus disease 2019 (COVID-19) worldwide, the resources needed to provide continuous kidney replacement therapy (CKRT) for patients with acute kidney injury or kidney failure may be threatened. This article summarizes subsisting strategies that can be implemented immediately. Pre-emptive weekly multicenter projections of CKRT demand based on evolving COVID-19 epidemiology and routine workload should be made. Corresponding consumables should be quantified and acquired, with diversification of sources from multiple vendors. Supply procurement should be stepped up accordingly so that a several-week stock is amassed, with administrative oversight to prevent disproportionate hoarding by institutions. Consumption of CKRT resources can be made more efficient by optimizing circuit anticoagulation to preserve filters, extending use of each vascular access, lowering blood flows to reduce citrate consumption, moderating the CKRT intensity to conserve fluids, or running accelerated KRT at higher clearance to treat more patients per machine. If logistically feasible, earlier transition to intermittent hemodialysis with online-generated dialysate, or urgent peritoneal dialysis in selected patients, may help reduce CKRT dependency. These measures, coupled to multicenter collaboration and a corresponding increase in trained medical and nursing staffing levels, may avoid downstream rationing of care and save lives during the peak of the pandemic. Complete author and article information provided before references.
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