As the number of SOTR increases, so does the incidence of fungal infections in that population. Surgery, along with antifungal therapy and a reduction in immunosuppression, are the cornerstones of treatment.

Reduction of immunosuppression is considered a reasonable adjuvant management strategy for transplant recipients with numerous or life-threatening skin cancers. Proposed guidelines are presented for the graduated reduction of immunosuppression coincident with the increasing skin cancer risks.

Background Hepatocellular carcinoma (HCC) is the leading cause of death in patients with cirrhosis, primarily due to failed early detection. HCC screening is recommended among individuals with cirrhosis using biannual abdominal ultrasound, for earlier tumor detection, administration of curative treatment, and improved survival. Surveillance by imaging with or without biomarkers such as alpha-fetoprotein (AFP) remains suboptimal for early stage HCC detection. Here we report on the development and assessment of methylation biomarkers from liquid biopsies for HCC surveillance in cirrhotic patients. Methods DNA methylation markers including the HCCBloodTest (Epigenomics AG) and a DNA-methylation panel established by next generation sequencing (NGS) were assessed using a training/testing design. The NGS panel algorithm was established in a training study (41 HCC patients; 46 cirrhotic non-HCC controls). For testing, plasma samples were obtained from cirrhotic patients (Child class A or B) with (60) or without (103) early stage HCC (BCLC stage 0, A, B). The assays were then tested using blinded sample sets and analyzed by preset algorithms. Results The HCCBloodTest and the NGS panel exhibited 76.7% and 57% sensitivities at 64.1% and 97% specificity, respectively. In a post-hoc analysis, a combination of the NGS panel with AFP (20 ng/mL) achieved 68% sensitivity at 97% specificity (AUC = 0.9). Conclusions Methylation biomarkers in cell free plasma DNA provide a new alternative for HCC surveillance. Multiomic panels comprising DNA methylation markers with other biological markers, such as AFP, provide an option to further increase the overall clinical performance of surveillance via minimally invasive blood samples. Trial Registration: Test set study—ClinicalTrials.gov (NCT03804593) January 11, 2019, retrospectively registered.

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Antibody-mediated rejection (ABMR) is implicated in 45% of renal allograft failure and 57% of late allograft dysfunction. Peritubular capillary C4d is a specific but insensitive marker of ABMR. The 2013 Banff Conference ABMR revised criteria included C4d-negative ABMR with evidence of endothelial-antibody interaction. We hypothesized that endothelial activation and lymphangiogenesis are increased with C4d-negative ABMR, and correlate with intra-graft T-regulatory cells (Tregs) and T-helper 17 (Th17). Seventy-four renal transplant biopsies were selected to include: a) ABMR with C4d Banff scores ≥2 (n=35); b) variable microvascular injury (MI) and C4d score <2 (n=24); c) variable MI and C4d score=0 (n=15). Controls included normal pre-implantation donor kidneys (n=5). Immunohistochemistry for endothelial activation [P- and E- selectins (SEL)], lymphangiogenesis (D2-40), Tregs (FOXP3), and Th17 (STAT3) was performed. Microvessel and inflammatory infiltrate density was assessed morphometrically in interstitium and peritubular capillaries. All transplants had significantly higher microvessel and lymph vessel density compared to normal. Increased expression of markers of endothelial activation predicted transplant glomerulopathy (P-SEL, p=0.003). Increased P-SEL and D2-40 were associated with longer interval from transplant to biopsy (p=0.005). All three markers were associated with increased interstitial fibrosis, tubular atrophy and graft failure (P-SEL, p<0.001; E-SEL, p=0.0011; D2-40, p=0.012). There was no association with the intragraft FOXP3/STAT3 ratio. We conclude that endothelial activation and lymphangiogenesis could represent a late response to injury leading to fibrosis and progression of kidney damage, and are independent of the intragraft FOXP3/STAT3 ratio. Our findings support the therapeutic potential of specifically targeting endothelial activation.

We present four patients who underwent simultaneous liver-kidney transplantation (SLK) and were diagnosed with calciphylaxis, also known as calcific uremic arteriolopathy (CUA). Common characteristics included high MELD scores (mean 35.2 AE 4.8) and advanced renal disease (duration range 6-44 weeks). CUA was diagnosed within the first 2 months post-SLK based on clinical features. Severe morbidity and prolonged hospital stay were observed and one of the patients died secondary to sepsis. Treatment included metabolic support, wound care, calcium level correction and use of sodium thiosulphate. CUA should be considered in the presence of painful dermatologic changes in patients status post SLK.

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