Donor genetic variants as risk factors for thrombosis after liver transplantation: A genome-wide association study

Thrombosis after liver transplantation substantially impairs graft- and patient survival. Inevitably, heritable disorders of coagulation originating in the donor liver are transmitted by transplantation. We hypothesized that genetic variants in donor thrombophilia genes are associated with increased risk of posttransplant thrombosis. We genotyped 775 donors for adult recipients and 310 donors for pediatric recipients transplanted between 1993 and 2018. We determined the association between known donor thrombophilia gene variants and recipient posttransplant thrombosis. In addition, we performed a genome-wide association study (GWAS) and meta-analyzed 1085 liver transplantations. In our donor cohort, known thrombosis risk loci were not associated with posttransplant thrombosis, suggesting that it is unnecessary to exclude liver donors based on thrombosis-susceptible polymorphisms. By performing a meta-GWAS from children and adults, we identified 280 variants in 55 loci at suggestive genetic significance threshold. Downstream prioritization strategies identified biologically plausible candidate genes, among which were AK4 (rs11208611-T, p = 4.22 × 10⁻⁰⁵) which encodes a protein that regulates cellular ATP levels and concurrent activation of AMPK and mTOR, and RGS5 (rs10917696-C, p = 2.62 × 10⁻⁰⁵) which is involved in vascular development. We provide evidence that common genetic variants in the donor, but not previously known thrombophilia-related variants, are associated with increased risk of thrombosis after liver transplantation.     

Patient Satisfaction and Quality of Life Among Adult Women with Androgenetic Alopecia Using 5% Topical Minoxidil

BACKGROUND: Androgenetic alopecia (AGA) is a common, genetically predisposed condition that begins after puberty and whose frequency increases with age; although biologically benign, AGA can impact patients both psychologically and socially, contributing to an impairment on their quality of life. OBJECTIVE: We sought to evaluate the psychological, social, and quality of life impairments inherent in women with AGA using 5% minoxidil daily for at least six months. DESIGN: Thirty-one women with diffuse central hair thinning and shaft miniaturization who were using 5% minoxidil daily for at least six months responded to a clinical questionnaire and underwent trichoscopy. RESULTS: 83.9 percent (n=26) of the participants reported they were satisfied with the 5% minoxidil treatment and its convenience. Hair loss influenced social life in 54.8 percent (n=17) of the respondents and choice of hair cut/hairstyle in 87.1 percent (n=27) of respondents. For 51.6 percent (n=16) hair loss was slightly increased, although it did not increase after beginning treatment. A frontoparietal pattern (74.2%, n=23), very low capillary density (61.3%, n=19), trichodynia (32.3%, n=10), and negative traction test (100%, n=31) were also observed. Miniaturization occurred in 100 percent (n=31) of patients, frontal/occipital hair thickness was reduced in 83.9 percent (n=26), and more than 10 percent of velus hair in the frontal area was observed in 83.9 percent (n=26) of patients. The number of hair shafts per follicular unit was reduced in 67.7 percent (n=21), and a higher frontal to occipital ratio of follicular units with one hair shaft was seen in 74.2 percent (n=23) of patients. Empty follicles, large numbers of peripillar brownish halo, scalp pigmentation, mild Ludwig''s baldness degree, and quality of life scores of 4±3.5 points were observed. CONCLUSION: Our results indicate that patient satisfaction and quality of life of women with AGA on 5% topical minoxidil are high, although hair loss influences daily habits and social life.     

Pseudoangiosarcomatous squamous cell carcinoma: first case report on penis

Pseudoangiosarcomatous squamous cell carcinoma, also called pseudovascular, pseudoangiomatoid or adenoid pseudovascular carcinoma, is an uncommon and highly aggressive variant of squamous cell carcinoma. Histologically, it is characterized by proliferation of atypical keratinocytes with acantholysis and formation of pseudovascular spaces, forming anastomosed channels lined with neoplastic cells that invade the dermis. These cells are positive for cytokeratin and negative for vascular markers such as CD31 and CD34. There are few reports of this variant in the literature. Skin, breast, lung and vulva involvement have been described, but to the best of our knowledge, no cases involving the penis has been described. This study aims to describe the first case of angiosarcomatous squamous cell carcinoma of the penis. The patient presented with a painful lesion in the penis associated with urinary retention. Macroscopic findings exhibited an ulcerative vegetating lesion that involving the entire glans and part of the penile body, as well as infiltration of penile structures and scrotal skin. Microscopy shows atypical proliferation of sarcomatous keratinocyte pattern mimicking vascular spaces. Human papilloma virus (HPV) biomarkers and polymerase chain reaction (PCR) were all negative. Advanced penile squamous cell carcinoma with aggressive lymph node metastasis. This report presents the first case of penile pseudoangiosarcomatous squamous cell carcinoma, as an important differential diagnosis.