Production of haploid gametes from diploid progenitor cells is mediated by a specialized cell division, meiosis, where two divisions, meiosis I and II, follow a single S phase. Errors in progression from meiosis I to meiosis II lead to aneuploid and polyploid gametes, but the regulatory mechanisms controlling this transition are poorly understood. Here, we demonstrate that the conserved kinase Ime2 regulates the timing and order of the meiotic divisions by controlling translation. Ime2 coordinates translational activation of a cluster of genes at the meiosis I-meiosis II transition, including the critical determinant of the meiotic chromosome segregation pattern CLB3. We further show that Ime2 mediates translational control through the meiosis-specific RNA-binding protein Rim4. Rim4 inhibits translation of CLB3 during meiosis I by interacting with the 59 untranslated region (UTR) of CLB3. At the onset of meiosis II, Ime2 kinase activity rises and triggers a decrease in Rim4 protein levels, thereby alleviating translational repression. Our results elucidate a novel developmentally regulated translational control pathway that establishes the meiotic chromosome segregation pattern.

In the United States, there are significant geographic disparities in the time to transplantation for patients with hepatocellular carcinoma (HCC); it is possible that rapid transplantation contributes to higher rates of posttransplant HCC recurrence because there is insufficient time for the tumor biology to manifest. In this study, we compared HCC recurrence in rapid transplant patients and their slower transplant counterparts. We identified adult liver transplantation (LT) candidates in the Organ Procurement and Transplantation Network/United Network for Organ Sharing (UNOS) data set who were granted an initial exception for an HCC diagnosis between January 1, 2006 and September 30, 2010 and underwent transplantation in the same time window. Patients were followed until HCC recurrence, non–HCC-related death, or last follow-up. The cumulative incidence of HCC recurrence was compared for patients waiting ≤120 days and patients waiting >120 days from an HCC exception to LT. The association between the risk of posttransplant recurrence and the wait time was further evaluated via competing risks regression with the Fine and Gray model. For 5002 LT recipients with HCC, the median wait time from an exception to LT was 77 days, and it varied from 30 to 169 days by UNOS region. The cumulative incidence of posttransplant HCC recurrence was 3.3% [95% confidence interval (CI) = 2.8%–3.8%] and 5.6% (95% CI = 5.0%–6.3%) within 1 and 2 years, respectively. The rate of observed recurrence within 1 year of transplantation was significantly lower for patients waiting >120 days versus patients waiting ≤120 days (2.2% versus 3.9%, P = 0.002); however, the difference did not persist at 2 years (5.0% versus 5.9%, P = 0.09). After we accounted for clinical factors, the HCC recurrence risk was reduced by 40% for patients waiting >120 days (subhazard ratio = 0.6, P = 0.005). In conclusion, the risk of HCC recurrence within the first year after transplantation may be lessened by the institution of a mandatory waiting time after an exception is granted.

Current guidelines recommend ultrasound (US) for hepatocellular carcinoma (HCC) surveillance in cirrhosis. We assess predictors of decreased US sensitivity for detecting HCC. At a single center in the United States, all HCC patients evaluated for liver transplantation (LT) received an abdominal US. From 2007-2015, consecutive patients presenting for untreated lesions found on computed tomography (CT) or magnetic resonance imaging (MRI) within 3 months of US were compared with US findings. Multivariate logistic regression models compared US sensitivities by patient characteristics. Of 1007 patients completing LT evaluation, 47.5% had indeterminate or previously treated nodules and were excluded; 10.4% had imaging that was too far apart or nondiagnostic. Median Model for End-Stage Liver Disease (MELD) of the cohort (n= 352) was 11 (interquartile range [IQR], 9-14), median body mass index (BMI) was 28 kg/m (IQR, 25-32 kg/m ), 39% had received locoregional therapy, and 10% had moderate/large ascites. Per-patient sensitivity of US compared with CT/MRI was 0.82 (95% confidence interval, 0.76-0.86). Patients with BMI ≥ 30 kg/m had a US sensitivity of 0.76 versus 0.87 for BMI < 30 kg/m (P = 0.01). MELD and ascites did not affect sensitivity. US sensitivity was decreased in patients with nonalcoholic steatohepatitis (NASH) versus other etiologies (0.59 versus 0.84; P = 0.02). Relative to CT/MRI, US is significantly less sensitive in patients with NASH or BMI ≥ 30 kg/m . Further study is necessary to examine the added value of cross-sectional imaging for patients with NASH or obesity.

Background Textbook outcome (TO) is an emerging concept within multiple surgical domains, which represents a novel effort to define a standardized, composite quality benchmark based on multiple postoperative endpoints that represent the ideal ''textbook'' hospitalization. We sought to define TO for liver transplantation (LT) using a cohort from a high procedural volume center. Methods Patients who underwent LT at our institution between 2014 and 2017 were eligible for the study. The definition of TO was determined by clinician consensus at our institution to include freedom from: mortality within 90 days, primary allograft non-function, early allograft dysfunction (EAD), rejection within 30 days, readmission with 30 days, readmission to the ICU during index hospitalization, hospital length of stay [ 75th percentile of all liver transplant patients, red blood cell (RBC) transfusion requirement greater than the 75th percentile for all liver transplant patients, Clavien-Dindo Grade III complication (re-intervention), and major intraoperative complication.Results Two hundred and thirty-one liver transplants with complete data were performed within the study period. Of those, 71 (31%) achieved a TO. Overall, the most likely event to lead to failure to achieve TO was readmission within 30 days (n = 57, 37%) or reoperation (n = 49, 32%). Overall and rejection-free survival did not differ significantly between the 2 groups. Interestingly, patients who achieved TO incurred approximately $60,000 less in total charges than those who did not. When we limit this to charges specifically attributable to the transplant episode, the difference was approximately $50,000 and remained significantly less for those that achieved TO. Conclusions Here, we present the first definition of TO in LT. Though not associated with long-term outcomes, TO in LT is associated with a significantly lower charges and costs of the initial hospitalization. A multi-institutional study to validate this definition of TO is warranted.