Prevalence of post-liver transplant complications and NASH-related cirrhosis in postmenopausal women.

INTRODUCTION AND OBJECTIVES: Compared to premenopausal women, postmenopausal women are at greater risk of developing NAFLD and NASH, two common indications for liver transplantation (LT). We aim to determine the prevalence of NASH-related cirrhosis in postmenopausal women from a cohort of LT patients and investigate their post-LT complications. MATERIALS AND METHODS: Chart review of 1200 LT patients from 2002-2020 was performed. Postmenopausal women were defined as women over 51 and compared to a control group of men over 51. Prevalence of LT indications was determined. Subgroup analysis assessed cardiovascular disease risk. BMI and ASCVD risk scores were calculated at the time of LT and after 1 year. RESULTS: 510 patients met the inclusion criteria: 189 (37.1%) women and 321 (62.9%) men. The most common indication was NASH for women (26.5%, p<0.001) and alcohol-related cirrhosis for men (23.1%). 53 men and 46 women underwent subgroup analysis. There was no significant difference in BMI or ASCVD 10-year risk post-LT between sexes. MI occurred more in men (n=9.17%) than women (n=1, 2%, p=0.015), with no significant differences in CAD, CHF, or stroke. LT complications occurred less in men (n=5.9%) than women (n=20, 43%, p=0.0001). CONCLUSIONS: Postmenopausal women were significantly more likely to have NASH as an indication for LT than men. Postmenopausal women had greater weight gain and more noncardiac complications than men. Women did not have increased cardiovascular outcomes, ASCVD risk, or mortality. Diet education and weight control in postmenopausal women with existing risk factors for NASH should be encouraged to modulate health outcomes.

Hemorrhage Sites and Mitigation Strategies After Pancreaticoduodenectomy.

Importance: Postpancreatectomy hemorrhage is an uncommon but highly morbid complication of pancreaticoduodenectomy. Clinical evidence often draws suspicion to the gastroduodenal artery stump, even without a clear source. Objective: To determine the frequency of gastroduodenal artery bleeding compared to other sites and the results of mitigation strategies. Design, Setting, and Participants: This cohort study involved a retrospective analysis of data for consecutive patients who had pancreaticoduodenectomy from 2011 to 2021 at Memorial Sloan Kettering Cancer Center (MSK) and Thomas Jefferson University Hospital (TJUH). Exposures: Demographic, perioperative, and disease-related variables. Main Outcomes and Measures: The incidence, location, treatment, and outcomes of primary (initial) and secondary (recurrent) hemorrhage requiring invasive intervention were analyzed. Imaging studies were re-reviewed by interventional radiologists to confirm sites. Results: Inclusion criteria were met by 3040 patients (n = 1761 MSK, n = 1279 TJUH). Patients from both institutions were similar in age (median [IQR] age at MSK, 67 [59-74] years, and at TJUH, 68 [60-75] years) and sex (at MSK, 814 female [46.5%] and 947 male [53.8%], and at TJUH, 623 [48.7%] and 623 male [51.3%]). Primary hemorrhage occurred in 90 patients (3.0%), of which the gastroduodenal artery was the source in 15 (16.7%), unidentified sites in 24 (26.7%), and non-gastroduodenal artery sites in 51 (56.7%). Secondary hemorrhage occurred in 23 patients; in 4 (17.4%), the gastroduodenal artery was the source. Of all hemorrhage events (n = 117), the gastroduodenal artery was the source in 19 (16.2%, 0.63% incidence in all pancreaticoduodenectomies). Gastroduodenal artery hemorrhage was more often associated with soft gland texture (14 [93.3%] vs 41 [62.1%]; P = .02) and later presentation (median [IQR], 21 [15-26] vs 10 days [5-18]; P = .002). Twenty-three patients underwent empirical gastroduodenal artery embolization or stent placement, 7 (30.4%) of whom subsequently experienced secondary hemorrhage. Twenty percent of all gastroduodenal artery embolizations/stents (8/40 patients), including 13% (3/13 patients) of empirical treatments, were associated with significant morbidity (7 hepatic infarction, 4 biliary stricture), with a 90-day mortality rate of 38.5% (n = 5) for patients with these complications vs 7.8% without (n = 6; P = .008). Ninety-day mortality was 12.2% (n = 11) for patients with hemorrhage (3 patients [20%] with primary gastroduodenal vs 8 [10.7%] for all others; P = .38) compared with 2% (n = 59) for patients without hemorrhage. Conclusions and Relevance: In this study, postpancreatectomy hemorrhage was uncommon and the spectrum was broad, with the gastroduodenal artery responsible for a minority of bleeding events. Empirical gastroduodenal artery embolization/stent without obvious sequelae of recent hemorrhage was associated with significant morbidity and rebleeding and should not be routine practice. Successful treatment of postpancreatectomy hemorrhage requires careful assessment of all potential sources, even after gastroduodenal artery mitigation.

The role of RNA binding proteins in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is one of the leading causes of overall cancer deaths worldwide with limited therapeutic options. Due to the heterogeneity of HCC pathogenesis, the molecular mechanisms underlying HCC development are not fully understood. Emerging evidence indicates that RNA-binding proteins (RBPs) play a vital role throughout hepatocarcinogenesis. Thus, a deeper understanding of how RBPs contribute to HCC progression will provide new tools for early diagnosis and prognosis of this devastating disease. In this review, we summarize the tumor suppressive and oncogenic roles of RBPs and their roles in hepatocarcinogenesis. The diagnostic and therapeutic potential of RBPs in HCC, including their limitations, are also discussed.

Comprehensive Review of Cardiovascular Disease Risk in Nonalcoholic Fatty Liver Disease.

Nonalcoholic Fatty Liver Disease (NAFLD) is a growing global phenomenon, and its damaging effects in terms of cardiovascular disease (CVD) risk are becoming more apparent. NAFLD is estimated to affect around one quarter of the world population and is often comorbid with other metabolic disorders including diabetes mellitus, hypertension, coronary artery disease, and metabolic syndrome. In this review, we examine the current evidence describing the many ways that NAFLD itself increases CVD risk. We also discuss the emerging and complex biochemical relationship between NAFLD and its common comorbid conditions, and how they coalesce to increase CVD risk. With NAFLD's rising prevalence and deleterious effects on the cardiovascular system, a complete understanding of the disease must be undertaken, as well as effective strategies to prevent and treat its common comorbid conditions.

New Populations of Sclerotinia sclerotiorum from Lettuce in California and Peas and Lentils in Washington.

ABSTRACT Four populations of Sclerotinia sclerotiorum in North America were inferred previously, based on analyses of both rapidly evolving markers (DNA fingerprint and mycelial compatiblity), and multilocus DNA sequence spanning the range between fast and slow evolution. Each population was defined as an interbreeding unit of conspecific individuals sharing a common recent ancestor and arising in a unique evolutionary event. The present study applies this standard to extend characterization of S. sclerotiorum populations to the Western United States. Isolates of S. sclerotiorum (N = 294) were determined to represent three genetically differentiated populations: California (CA, lettuce), Washington (WA, pea/lentil), and Ontario (ON, lettuce). CA was the most diverse population yet sampled in North America. Clonality was detected in ON and WA. No DNA fingerprints were common among the populations. The index of association (I(A)), based on fingerprint, was closer to zero (0) for CA than it was for the other populations. High diversity and lack of association of markers in California are consistent either with genetic exchange and recombination, or with large population size and high standing genetic variation. Intra- and interlocus conflict among three DNA sequence loci was consistent with recombination. The coalescent IGS genealogy confirmed subdivision and showed CA to be older than WA or ON. The Nearest Neighbor statistic on combined data confirmed subdivision among all present and previously defined populations. All isolates had both MAT1-1 and MAT1-2, consistent with uniform homothallism.

An optimized method for mycelial compatibility testing in Sclerotinia sclerotiorum.

Classification of isolates into mycelial compatibility groups (MCGs) is used routinely in many laboratories as a quick marker for genotyping Sclerotinia sclerotiorum within populations. Scoring each new sample requires optimization of standardized conditions to support adequate growth of all paired isolates. Appropriate conditions for growth are especially important because diverse compatibility reactions are difficult to categorize and score (e.g., in samples from populations with high genetic diversity, such as those that receive immigration from genetically diverse sources or those that deviate from strict clonality). The current standard medium for MCG testing can be inhibitory to isolates from some samples, confounding scoring of compatibility. We identified two foci for optimization: (i) choice of medium, in this experiment, Patterson's medium amended with red food coloring (termed modified Patterson's medium, MPM, the current standard medium) versus potato dextrose agar (PDA) and (ii) amount of McCormick's red food coloring amended to the growth medium. The red food coloring often yields a red reaction line in incompatible interactions; alternative incompatible reactions are a line of thick or thin hyphae. Based on results to date, self-self pairings of S. sclerotiorum are compatible and are a reliable standard for scoring compatible self-nonself mycelial interactions. PDA amended with 75 microl/L of McCormick's red food coloring was identified as optimal for isolates inhibited by MPM from a highly diverse, recombining population sample. This precisely amended PDA was also suitable for isolates from highly clonal populations that were not inhibited by MPM or by higher concentrations of red food coloring. Under the optimized, standardized conditions all paired isolates grew together and produced interactions that could be scored in repeatedly identifiable categories, compatible or incompatible. Workers are advised to optimize conditions before screening a new population sample.