The 2007 Banff working classification of skin-containing Tissue Allograft Pathology addressed only acute T cell-mediated rejection in skin. We report the longitudinal long-term histological follow-up of six face transplant recipients, focusing on chronic and mucosal rejection. We identified three patterns suggestive of chronic rejection (lichen planus-like, vitiligo-like and scleroderma-like). Four patients presented lichen planus-like and vitiligo-like chronic rejection at 52 ± 17 months posttransplant with severe concomitant acute T cell-mediated rejection. After lichen planus-like rejection, two patients developed scleroderma-like alterations. Graft vasculopathy with C4d deposits and de novo DSA led to subsequent graft loss in one patient. Chronic active rejection was frequent and similar patterns were noted in mucosae.  https://www.selleckchem.com/products/Pomalidomide(CC-4047).html  Concordance between 124 paired skin and mucosal biopsies acute rejection grades was low (κ = 0.2, p = .005) but most grade 0/I mucosal rejections were associated with grade 0/I skin rejections. We defined discordant (grade≥II mucosal rejection and grade 0/I skin rejection) (n = 55 [70%]) and concordant (grade≥II rejection in both biopsies) groups. Mucosal biopsies of the discordant group displayed lower intra-epithelial GranzymeB/FoxP3 ratios suggesting a less aggressive phenotype (p = .08). The grading system for acute rejection in mucosa may require phenotyping. Whether discordant infiltrates reflect a latent allo-immune reaction leading to chronic rejection remains an open question.
  The optimal treatment for gastric varices (GVs) is a topic that remains open for study. This study compared the efficacy and safety of endoscopic cyanoacrylate injection and balloon-occluded retrograde transvenous obliteration (BRTO) to prevent rebleeding in patients with cirrhosis and GVs after primary hemostasis.
 
  Patients with cirrhosis and history of bleeding from gastroesophageal varices type 2 or isolated gastric varices type 1 were randomized to cyanoacrylate injection (n=32) or BRTO treatment (n=32). Primary outcomes were gastric variceal rebleeding or all-cause rebleeding. Patient characteristics were well balanced between two groups. Mean follow-up time was 27.1±12.0months in a cyanoacrylate injection group and 27.6±14.3months in a BRTO group. Probability of gastric variceal rebleeding was higher in the cyanoacrylate injection group than in the BRTO group (P=0.024). Probability of remaining free of all-cause rebleeding at 1 and 2years for cyanoacrylate injection versus BRTO was 77% versus 96.3% and 65.2% versus 92.6% (P=0.004). Survival rates, frequency of complications, and worsening of esophageal varices were similar in both groups. BRTO resulted in fewer hospitalizations, inpatient stays, and lower medical costs.
 
  BRTO is more effective than cyanoacrylate injection in preventing rebleeding from GVs, with similar frequencies of complications and mortalities.
 BRTO is more effective than cyanoacrylate injection in preventing rebleeding from GVs, with similar frequencies of complications and mortalities.The thermotolerant methylotrophic yeast Ogataea thermomethanolica TBRC656 is a potential host for heterologous protein production. However, overproduction of heterologous protein can induce cellular stress and limit the level of its secretion. To improve the secretion of heterologous protein, we identified the candidate proteins with altered production during production of heterologous protein in O. thermomethanolica by using a label-free comparative proteomic approach. Four hundred sixty-four proteins with various biological functions showed differential abundance between O. thermomethanolica expressing fungal xylanase (OT + Xyl) and a control strain. The induction of proteins in transport and proteasomal proteolysis was prominently observed. Eight candidate proteins involved in cell wall biosynthesis (Chs3, Gas4), chaperone (Sgt2, Pex19), glycan metabolism (Csf1), protein transport (Ypt35), and vacuole and protein sorting (Cof1, Npr2) were mutated by a CRISPR/Cas9 approach. An Sgt2 mutant showed higher phytase and xylanase activity compared with the control strain (13%-20%), whereas mutants of other genes including Cof1, Pex19, Gas4, and Ypt35 showed lower xylanase activity compared with the control strain (15%-25%). In addition, an Npr2 mutant showed defective growth, while overproduction of Npr2 enhanced xylanase activity. These results reveal genes that can be mutated to modulate heterologous protein production and growth of O. thermomethanolica TBRC656.
  To investigate the relationship between obesity and sarcopenia in relation to overall survival (OS) and disease-specific survival (DSS) in high-grade endometrial cancer patients.
 
  We conducted a retrospective study in women diagnosed with high-grade endometrial cancer (EC) between February 2006 and August 2017 in the Royal Cornwall Hospital who had abdominal computerized tomography (CT)-scan as part of routine staging work-up. Sarcopenia was assessed by measuring psoas-, paraspinal- and abdominal wall muscles on CT and defined by skeletal muscle index ≤41cm
  /m
  . Sarcopenic obesity was defined as sarcopenia combined with body mass index (BMI) ≥30kg/m
  .
 
  A total of 176 patients with median age of 70years and median BMI of 29.4kg/m
  were included in the study. The majority of patients (38%) had endometrioid type histology. Sarcopenia was not associated with OS (P=0.951) or DSS (P=0.545) However, in multivariate analysis, sarcopenic obesity was associated with reduced OS in endometrioid endometrial cancer (EEC) patients (P=0.048).
 
  Sarcopenic obesity is associated with OS in high-grade EEC patients, while sarcopenia without obesity is not related to OS or DSS in high-grade EC. In non-endometrioid endometrial cancer, there is no association between sarcopenic obesity and survival.
 Sarcopenic obesity is associated with OS in high-grade EEC patients, while sarcopenia without obesity is not related to OS or DSS in high-grade EC. In non-endometrioid endometrial cancer, there is no association between sarcopenic obesity and survival.We aimed to assess whether the presence of atypical mitotic figures (AMF) in smooth muscle tumors of uncertain malignant potential (STUMP) of the uterus and uterine adnexa is associated with increased risk of recurrence, and the association of AMF with the Stanford criteria, that is, significant cytologic atypia, mitotic index ≥ 10/10HPF, and coagulative tumor cell necrosis (CTCN). A systematic review was performed to identify all studies reporting the presence of AMF and oncologic outcomes in STUMP series. Fisher's exact test was used to assess the association of AMF with the three Stanford parameters. Kaplan-Meier and Cox regression survival analyses with hazard ratio (HR) calculation were performed to assess the association between AMF and STUMP recurrence. A p-value less then 0.05 was considered significant. Five studies with 80 STUMPs were included, out of which 23.8% had AMF. AMF were significantly associated with the presence of significant atypia (p = 0.023), but not with the presence of a mitotic index ≥ 10/10HPF (p = 0.