Dibutyl phthalate released by solitary female locusts mediates sexual communication at low density.

Sex pheromones play a crucial role in mate location and reproductive success. Insects face challenges in finding mates in low-density environments. The population dynamics of locusts vary greatly, ranging from solitary individuals to high-density swarms, leading to multiple-trait divergence between solitary and gregarious phases. However, differences in sexual communication between solitary and gregarious locusts have not been sufficiently explored. Herein, we found that solitary locusts but not gregarious ones heavily rely on a single compound, dibutyl phthalate (DBP), for sexual communication. DBP is abundantly released by solitary female locusts and elicits strong attraction of male solitary and gregarious locusts. Solitary adult males display much higher electrophysiological responses to DBP than adult females. Additionally, LmigOr13 was identified as the DBP-specific odorant receptor expressed in neurons housed in basiconic sensilla. Male LmigOr13-/- mutants generated by CRISPR/Cas9 have low electrophysiological responses and behavioral attraction to DBP in both laboratory and field cage experiments. Notably, the attractiveness of DBP to male locusts becomes more evident at lower population densities imposed by controlling the cage size. This finding sheds light on the utilization of a sex pheromone to promote reproductive success in extremely low-density conditions and provides important insights into alternative approaches for population monitoring of locusts.

Development of a liver disease-specific large language model chat interface using retrieval-augmented generation.

BACKGROUND AND AIMS: Large language models (LLMs) have significant capabilities in clinical information processing tasks. Commercially available LLMs, however, are not optimized for clinical uses and are prone to generating hallucinatory information. Retrieval-augmented generation (RAG) is an enterprise architecture that allows the embedding of customized data into LLMs. This approach "specializes" the LLMs and is thought to reduce hallucinations. APPROACH AND RESULTS: We developed "LiVersa," a liver disease-specific LLM, by using our institution's protected health information-complaint text embedding and LLM platform, "Versa." We conducted RAG on 30 publicly available American Association for the Study of Liver Diseases guidance documents to be incorporated into LiVersa. We evaluated LiVersa's performance by conducting 2 rounds of testing. First, we compared LiVersa's outputs versus those of trainees from a previously published knowledge assessment. LiVersa answered all 10 questions correctly. Second, we asked 15 hepatologists to evaluate the outputs of 10 hepatology topic questions generated by LiVersa, OpenAI's ChatGPT 4, and Meta's Large Language Model Meta AI 2. LiVersa's outputs were more accurate but were rated less comprehensive and safe compared to those of ChatGPT 4. RESULTS: We evaluated LiVersa's performance by conducting 2 rounds of testing. First, we compared LiVersa's outputs versus those of trainees from a previously published knowledge assessment. LiVersa answered all 10 questions correctly. Second, we asked 15 hepatologists to evaluate the outputs of 10 hepatology topic questions generated by LiVersa, OpenAI's ChatGPT 4, and Meta's Large Language Model Meta AI 2. LiVersa's outputs were more accurate but were rated less comprehensive and safe compared to those of ChatGPT 4. CONCLUSIONS: In this demonstration, we built disease-specific and protected health information-compliant LLMs using RAG. While LiVersa demonstrated higher accuracy in answering questions related to hepatology, there were some deficiencies due to limitations set by the number of documents used for RAG. LiVersa will likely require further refinement before potential live deployment. The LiVersa prototype, however, is a proof of concept for utilizing RAG to customize LLMs for clinical use cases.

The association between mean arterial pressure and acute kidney injury reversal among patients with decompensated cirrhosis.

BACKGROUND AND AIMS: This study informs how mean arterial pressure (MAP) impacts acute kidney injury (AKI) recovery among all patients hospitalized with cirrhosis, regardless of etiology. APPROACH AND RESULTS: We identified incident AKI episodes among subjects in our cohort of patients with decompensated cirrhosis. AKI was defined as a ≥50% increase in creatinine from an outpatient baseline (≥7 days prior) that required hospitalization. Linear mixed effects models were completed to determine the impact between AKI recovery, MAP, and time. To determine the impact of MAP on AKI reversal, we completed time-dependent Cox regression models with time beginning at the time of peak creatinine and ending at death, discharge, or AKI reversal, among those hospitalized with AKI and those with persistent AKI (≥48 h) We identified 702 hospitalized patients with cirrhosis with AKI. We found those with AKI reversal had, on average, higher MAP (2.1 mm Hg, p <0.05) and a greater increase in MAP over time (0.1 mm Hg per hour, p <0.001). Among all 702 hospitalized patients with AKI and adjusted for confounders, each 5 mm Hg increase in MAP was associated with 1.07× the hazard of AKI reversal ( p <0.01). Similarly, among those with persistent AKI after adjusting for confounders, each 5 mm Hg increase in MAP was associated with a 1.19× greater likelihood of AKI reversal ( p <0.001). DISCUSSION: Our data demonstrate that MAP significantly increases the likelihood of AKI recovery regardless of severity or injury or AKI phenotype. We believe these data highlight the importance of MAP as a clinical tool to promote kidney function recovery among patients with cirrhosis hospitalized with AKI.

Outpatient mean arterial pressure: A potentially modifiable risk for acute kidney injury and death among patients with cirrhosis.

Mean arterial blood pressure (MAP), which decreases as portal hypertension progresses, may be a modifiable risk factor among patients with cirrhosis. We included adults enrolled in the Functional Assessment in Liver Transplantation study. We completed latent class trajectory analyses to define MAP trajectories. We completed time-dependent Cox-regression analyses to test the association between outpatient MAP and 3 cirrhosis-related outcomes: (1) stage 2 acute kidney injury (AKI), defined as a ≥200% increase in serum creatinine from baseline; (2) a 5-point increase in the MELD-Na score, defined as the incidence of increase from initial MELD-Na; (3) waitlist mortality, defined as death on the waitlist. For each outcome, we defined MAP cut points by determining the maximally selected Log-rank statistic after univariable Cox-regression analyses. Among the 1786 patients included in this analysis, our latent class trajectory analyses identified 3 specific outpatient MAP trajectories: "stable-low," "stable-high," and "increasing-to-decreasing." However, >80% of patients were in a "stable-low" trajectory. We found in adjusted analyses that outpatient MAP was associated with each of our outcomes: Stage 2 AKI (adjusted hazard ratio 0.88 per 10 mm Hg increase in MAP [95% CI: 0.79-0.99]); 5-point increase in MELD-Na (adjusted hazard ratio: 0.91 [95% CI: 0.86-0.96]; waitlist mortality (adjusted hazard ratio: 0.89 [95% CI: 0.81-0.96]). For each outcome, we found that an outpatient MAP of 82 mm Hg was most associated with outcomes ( p <0.05 for all). Our study informs the association between outpatient MAP and cirrhosis-related outcomes. These findings, coupled with the identification of specific thresholds, lay the foundation for the trial of targeted outpatient MAP modulation in patients with cirrhosis.

Clinical decision support and electronic interventions to improve care quality in chronic liver diseases and cirrhosis.

Significant quality gaps exist in the management of chronic liver diseases and cirrhosis. Clinical decision support systems-information-driven tools based in and launched from the electronic health record-are attractive and potentially scalable prospective interventions that could help standardize clinical care in hepatology. Yet, clinical decision support systems have had a mixed record in clinical medicine due to issues with interoperability and compatibility with clinical workflows. In this review, we discuss the conceptual origins of clinical decision support systems, existing applications in liver diseases, issues and challenges with implementation, and emerging strategies to improve their integration in hepatology care.

Breakthrough SARS-CoV-2 infection outcomes in vaccinated patients with chronic liver disease and cirrhosis: A National COVID Cohort Collaborative study.

BACKGROUND AND AIMS: Outcomes of breakthrough SARS-CoV-2 infections have not been well characterized in non-veteran vaccinated patients with chronic liver diseases (CLD). We used the National COVID Cohort Collaborative (N3C) to describe these outcomes. APPROACH AND RESULTS: We identified all CLD patients with or without cirrhosis who had SARS-CoV-2 testing in the N3C Data Enclave as of January 15, 2022. We used Poisson regression to estimate incidence rates of breakthrough infections and Cox survival analyses to associate vaccination status with all-cause mortality at 30 days among infected CLD patients. We isolated 278,457 total CLD patients: 43,079 (15%) vaccinated and 235,378 (85%) unvaccinated. Of 43,079 vaccinated patients, 32,838 (76%) were without cirrhosis and 10,441 (24%) with cirrhosis. Breakthrough infection incidences were 5.4 and 4.9 per 1000 person-months for fully vaccinated CLD patients without cirrhosis and with cirrhosis, respectively. Of the 68,048 unvaccinated and 10,441 vaccinated CLD patients with cirrhosis, 15% and 3.7%, respectively, developed SARS-CoV-2 infection. The 30-day outcome of mechanical ventilation or death after SARS-CoV-2 infection for unvaccinated and vaccinated CLD patients with cirrhosis were 15.2% and 7.7%, respectively. Compared to unvaccinated patients with cirrhosis, full vaccination was associated with a 0.34-times adjusted hazard of death at 30 days. CONCLUSIONS: In this N3C study, breakthrough infection rates were similar among CLD patients with and without cirrhosis. Full vaccination was associated with a 66% reduction in risk of all-cause mortality for breakthrough infection among CLD patients with cirrhosis. These results provide an additional impetus for increasing vaccination uptake in CLD populations.

Association between neighborhood-based material deprivation and liver transplant waitlist registrants demographics and mortality.

BACKGROUND & AIMS: Liver transplantation for alcohol-related liver disease (ARLD) has increased. We examined temporal trends in ARLD listing practices by neighborhood deprivation and evaluated the impact of neighborhood deprivation on waitlist mortality. METHODS: We included all adults > 18 years listed 2008-2019 in the UNOS registry. Our primary exposure was the neighborhood socioeconomic deprivation index based on patients' listing zip codes. We determined temporal trends in an ARLD listing diagnosis. We modeled ARLD listing diagnosis using logistic regression and waitlist mortality using Cox proportional hazards models. RESULTS: The waitlist contained an increasing proportion of patients listed with ARLD over the study period; however, this rate increased the least for patients from the most deprived tertile (p < .001). Patients from the most deprived tertile were the least likely to be listed with ARLD (OR: .97, 95CI: .95-.98). In our adjusted model, patients from the most deprived tertile had an increased hazard of waitlist mortality (OR: 1.10, 95CI: 1.06-1.14). CONCLUSION: Neighborhood deprivation was associated with a decreased likelihood of being listed with ARLD, suggesting that transplant for ARLD is inequitably available. The increased mortality associated with neighborhood deprivation demands future work to uncover the underlying reasons for this disparity.

Clinical Characteristics Associated With Posttransplant Survival Among Adults 70 Years Old or Older Undergoing Liver Transplantation.

GOALS: We sought to identify pre-liver transplantation (LT) characteristics among older adults associated with post-LT survival. BACKGROUND: The proportion of older patients undergoing deceased-donor liver transplantation (DDLT) has increased over time. STUDY: We analyzed adult DDLT recipients in the United Network for Organ Sharing registry from 2016 through 2020, excluding patients listed as status 1 or with a model of end-stage liver disease exceptions for hepatocellular carcinoma. Kaplan-Meier methods were used to estimate post-LT survival probabilities among older recipients (age ≥70 y). Associations between clinical covariates and post-LT mortality were assessed using Cox regressions. RESULTS: Of 22,862 DDLT recipients, 897 (4%) were 70 years old or older. Compared with younger recipients, older recipients had worse overall survival ( P < 0.01) (1 y: 88% vs 92%, 3 y: 77% vs 86%, and 5 y: 67% vs 78%). Among older adults, in univariate Cox regressions, dialysis [hazards ratio (HR): 1.96, 95% CI: 1.38-2.77] and poor functional status [defined as Karnofsky Performance Score (KPS) <40] (HR: 1.82, 95% CI: 1.31-2.53) were each associated with mortality, remaining significant on multivariable Cox regressions. The effect of dialysis and KPS <40 at LT on post-LT survival (HR: 2.67, 95% CI: 1.77-4.01) was worse than the effects of either KPS <40 (HR: 1.52, 95% CI: 1.03-2.23) or dialysis alone (HR: 1.44, 95% CI: 0.62-3.36). Older recipients with KPS >40 without dialysis had comparable survival rates compared with younger recipients ( P = 0.30). CONCLUSIONS: While older DDLT recipients had worse overall post-LT survival compared with younger recipients, favorable survival rates were observed among older adults who did not require dialysis and had poor functional status. Poor functional status and dialysis at LT may be useful to stratify older adults at higher risk for poor post-LT outcomes.

Recent advances in the synthesis of trifluoromethyl-containing heterocyclic compounds via trifluoromethyl building blocks.

Trifluoromethylated heterocyclic compounds have played an increasingly significant role in pharmaceuticals, agrochemicals, and materials. This is because the introduction of trifluoromethyl could enhance the lipophilicity, metabolic stability, and pharmacokinetic properties of heterocyclic drug molecules. Therefore, the synthesis of trifluoromethylated heterocyclics has become a major subject of research. The construction of trifluoromethylated heterocyclics via the annulation of trifluoromethyl building blocks with suitable partners has been proved to be a powerful strategy. In this review, we systematically summarize and discuss recent advances in the preparation of trifluoromethyl-containing heterocyclics via trifluoromethyl building block strategies over the period from 2019 to the present.

Risk factors for severe outcomes of coronavirus disease 2019 through the waves of the pandemic: Comparing patients with and without solid organ transplantation.

BACKGROUND: While coronavirus disease 2019 (COVID-19) is no longer a public health emergency, certain patients remain at risk of severe outcomes. To better understand changing risk profiles, we studied the risk factors for patients with and without solid organ transplantation (SOT) through the various waves of the pandemic. METHODS: Using the National COVID Cohort Collaborative we studied a cohort of adult patients testing positive for COVID-19 between January 1, 2020, and May 2, 2022. We separated the data into waves of COVID-19 as defined by the Centers for Disease Control. In our primary outcome, we used multivariable survival analysis to look at various risk factors for hospitalization in those with and without SOT. RESULTS: A total of 3,570,032 patients were captured. We found an overall risk attenuation of adverse COVID-19-associated outcomes over time. In both non-SOT and SOT populations, diabetes, chronic kidney disease, and congestive heart failure were risk factors for hospitalization. For SOT specifically, longer time periods between transplant and COVID-19 were protective and age was a risk factor. Notably, asthma was not a risk factor for major adverse renal cardiovascular events, hospitalization, or mortality in either group. CONCLUSIONS: Our study provides a longitudinal view of the risks associated with adverse COVID-related outcomes amongst SOT and non-SOT patients, and how these risk factors evolved over time. Our work will help inform providers and policymakers to better target high-risk patients.

Pharmacokinetics and tissue distribution of vigabatrin enantiomers in rats.

Purpose: To investigate the pharmacokinetics and tissue distribution of VGB racemate and its single enantiomers, and explore the potential of clinic development for single enantiomer S-VGB. Methods: In the pharmacokinetics study, male Sprague-Dawley rats were gavaged with VGB racemate or its single enantiomers dosing 50, 100 or 200 mg/kg, and the blood samples were collected during 12 h at regular intervals. In the experiment of tissue distribution, VGB and its single enantiomers were administered intravenously dosing 200 mg/kg, and the tissues including heart, liver, spleen, lung and kidney, eyes, hippocampus, and prefrontal cortex were separated at different times. The concentrations of R-VGB and S-VGB in the plasma and tissues were measured using HPLC. Results: Both S-VGB and R-VGB could be detected in the plasma of rats administered with VGB racemate, reaching Cmax at approximately 0.5 h with t1/2 2-3 h. There was no significant pharmacokinetic difference between the two enantiomers when VGB racemate was given 200 mg/kg and 100 mg/kg. However, when given at the dose of 50 mg/kg, S-VGB presented a shorter t1/2 and a higher Cl/F than R-VGB, indicating a faster metabolism of S-VGB. Furthermore, when single enantiomer was administered respectively, S-VGB presented a slower metabolism than R-VGB, as indicated by a longer t1/2 and MRT but a lower Cmax. Moreover, compared with the VGB racemate, the single enantiomers S-VGB and R-VGB had shorter t1/2 and MRT, higher Cmax and AUC/D, and lower Vz/F and Cl/F, indicating the stronger oral absorption and faster metabolism of single enantiomer. In addition, regardless of VGB racemate administration or single enantiomer administration, S-VGB and R-VGB had similar characteristics in tissue distribution, and the content of S-VGB in hippocampus, prefrontal cortex and liver was much higher than that of R-VGB. Conclusions: Although there is no transformation between S-VGB and R-VGB in vivo, those two enantiomers display certain disparities in the pharmacokinetics and tissue distribution, and interact with each other. These findings might be a possible interpretation for the pharmacological and toxic effects of VGB and a potential direction for the development and optimization of the single enantiomer S-VGB.

[Effect of Naotaifang on microglial polarization and glial scar following cerebral ischemia reperfusion injury].

This study aims to investigate the effect of Naotaifang(NTF) on the proteins associated with microglial polarization and glial scar in the rat model of cerebral ischemia reperfusion injury(CIRI). The CIRI model was established by middle cerebral artery occlusion/reperfusion. The 48 successfully modeled rats were randomized into model 7 d, model 14 d, NTF 7 d, and NTF 14 d groups(n=12). In addition, 12 SD rats were selected as the sham group. The NTF group was administrated with NTF suspension at 27 g·kg~(-1)·d~(-1) by gavage, and the sham, model 7 d, and model 14 d groups were administrated with the same volume of normal saline every day by gavage for 7 and 14 days, respectively. After the intervention, Longa score was evaluated. The infarct volume was measured by 2,3,5-triphenyl-2H-tetrazolium chloride(TTC) staining. Morris water maze and open field tests were carried out to evaluate the spatial learning, memory, cognitive function, and anxiety degree of rats. Hematoxylin-eosin(HE) staining was employed to observe the morphological structure and damage of the brain tissue. The immunofluorescence assay was employed to measure the expression of glial fibrillary acidic protein(GFAP) and glial scar. Western blot was employed to determine the protein levels of GFAP, neurocan, phosphacan, CD206, arginase-1(Arg-1), interleukin(IL)-1ß, IL-6, and IL-4. Compared with the sham, model 7 d and model 14 d groups showed cerebral infarction of different degrees, severe pathological injury of cerebral cortex and hippocampus, neurological impairment, reduced spatial learning and memory, cognitive dysfunction, severe anxiety, astrocyte hyperplasia, thickening penumbra glial scar, and up-regulated protein levels of IL-1ß, IL-6, GFAP, neurocan, phosphacan, CD206, and Arg-1(P<0.01). Compared with the model group, NTF 7 d and NTF 14 d groups improved spatial learning, memory, and cognitive function, reduced anxiety, improved nerve function, reduced cerebral infarction volume, reduced astrocyte hyperplasia, thinned penumbra glial scar, down-regulated the protein levels of GFAP, neurocan, phosphacan, IL-6, and IL-1ß, and up-regulated the protein levels of IL-4, CD206, and Arg-1(P<0.05 or P<0.01). NTF exerts a neuroprotective effect on CIRI by inducing the M2 polarization of microglia, inhibiting inflammatory response, and reducing the formation of glial scar.

Solvent-Controlled Enantiodivergent Construction of P(V)-Stereogenic Molecules via Palladium-Catalyzed Annulation of Prochiral N-Aryl Phosphonamides with Aromatic Iodides.

In this work, we describe an efficient and modular method for enantiodivergent accessing P(V)-stereogenic molecules by utilizing the catalytic atroposelective Catellani-type C-H arylation/desymmetric intramolecular N-arylation cascade reaction. The enantioselectivity of this protocol was proved to be tuned by the polarity of the solvent, thus providing a wide range of both chiral P(V)-stereogenic enantiomers in moderate to good yields with good to excellent enantiomeric excesses. Noteworthy is that the strategy developed herein represents an unprecedented example of solvent-dictated inversion of the enantioselectivity of P(V)-stereogenic compounds.

Predicting post-liver transplant outcomes in patients with acute-on-chronic liver failure using Expert-Augmented Machine Learning.

Liver transplantation (LT) is a treatment for acute-on-chronic liver failure (ACLF), but high post-LT mortality has been reported. Existing post-LT models in ACLF have been limited. We developed an Expert-Augmented Machine Learning (EAML) model to predict post-LT outcomes. We identified ACLF patients who underwent LT in the University of California Health Data Warehouse. We applied the RuleFit machine learning (ML) algorithm to extract rules from decision trees and create intermediate models. We asked human experts to rate the rules generated by RuleFit and incorporated these ratings to generate final EAML models. We identified 1384 ACLF patients. For death at 1 year, areas under the receiver-operating characteristic curve were 0.707 (confidence interval [CI] 0.625-0.793) for EAML and 0.719 (CI 0.640-0.800) for RuleFit. For death at 90 days, areas under the receiver-operating characteristic curve were 0.678 (CI 0.581-0.776) for EAML and 0.707 (CI 0.615-0.800) for RuleFit. In pairwise comparisons, both EAML and RuleFit models outperformed cross-sectional models. Significant discrepancies between experts and ML occurred in rankings of biomarkers used in clinical practice. EAML may serve as a method for ML-guided hypothesis generation in further ACLF research.

Racial/ethnic disparities in wait-list outcomes are only partly explained by socioeconomic deprivation among children awaiting liver transplantation.

BACKGROUND AND AIMS: Racial/ethnic minority children have worse liver transplant (LT) outcomes. We evaluated whether neighborhood socioeconomic deprivation affected associations between race/ethnicity and wait-list mortality. APPROACH AND RESULTS: We included children (age <18) listed 2005-2015 in the Scientific Registry of Transplant Recipients. We categorized patients as non-Hispanic White, Black, Hispanic, and other. We matched patient ZIP codes to a neighborhood socioeconomic deprivation index (range, 0-1; higher values indicate worse deprivation). Primary outcomes were wait-list mortality, defined as death/delisting for too sick, and receipt of living donor liver transplant (LDLT). Competing risk analyses modeled the association between race/ethnicity and wait-list mortality, with deceased donor liver transplant (DDLT) and LDLT as competing risks, and race/ethnicity and LDLT, with wait-list mortality and DDLT as competing risks. Of 7716 children, 17% and 24% identified as Black and Hispanic, respectively. Compared to White children, Black and Hispanic children had increased unadjusted hazard of wait-list mortality (subhazard ratio [sHR], 1.44; 95% CI, 1.18, 1.75 and sHR, 1.48; 95% CI, 1.25, 1.76, respectively). After adjusting for neighborhood deprivation, insurance, and listing laboratory Model for End-Stage Liver Disease/Pediatric End-Stage Liver Disease, Black and Hispanic children did not have increased hazard of wait-list mortality (sHR, 1.12; 95% CI, 0.91, 1.39 and sHR, 1.21; 95% CI, 1.00, 1.47, respectively). Similarly, Black and Hispanic children had a decreased likelihood of LDLT (sHR, 0.58; 95% CI, 0.45, 0.75 and sHR, 0.61; 95% CI, 0.49, 0.75, respectively). Adjustment attenuated the effect of Black and Hispanic race/ethnicity on likelihood of LDLT (sHR, 0.79; 95% CI, 0.60, 1.02 and sHR, 0.89; 95% CI, 0.70, 1.11, respectively). CONCLUSIONS: Household and neighborhood socioeconomic factors and disease severity at wait-list entry help explain racial/ethnic disparities for children awaiting transplant. A nuanced understanding of how social adversity contributes to wait-list outcomes may inform strategies to improve outcomes.

Associations between COVID-19 therapies and inpatient gastrointestinal bleeding: A multisite retrospective study.

Little data is available regarding the incidence of gastrointestinal bleeding in adults hospitalized with COVID-19 infection and the influence of patient comorbidities and demographics, COVID-19 therapies, and typical medications used. In this retrospective study, we utilized the National COVID Cohort Collaborative to investigate the primary outcome of the development of gastrointestinal bleeding in 512 467 hospitalized US adults (age >18 years) within 14 days of a COVID-19 infection and the influence of demographics, comorbidities, and selected medications. Gastrointestinal bleeding developed in 0.44% of patients hospitalized with COVID-19. Comorbidities associated with gastrointestinal bleeding include peptic ulcer disease (adjusted odds ratio [aOR] 10.2), obesity (aOR 1.27), chronic kidney disease (aOR 1.20), and tobacco use disorder (aOR 1.28). Lower risk of gastrointestinal bleeding was seen among women (aOR 0.76), Latinx (aOR 0.85), and vaccinated patients (aOR 0.74). Dexamethasone alone or with remdesivir was associated with lower risk of gastrointestinal bleeding (aOR 0.69 and aOR 0.83, respectively). Remdesivir monotherapy was associated with upper gastrointestinal bleeding (aOR 1.25). Proton pump inhibitors were more often prescribed in patients with gastrointestinal bleeding, likely representing treatment for gastrointestinal bleeding rather than a risk factor for its development. In adult patients hospitalized with COVID-19, the use of dexamethasone alone or in combination with remdesivir is negatively associated with gastrointestinal bleeding. Remdesivir monotherapy is associated with increased risk of upper gastrointestinal bleeding.

Change in Platelet Count after Transjugular Intrahepatic Portosystemic Shunt Creation: An Advancing Liver Therapeutic Approaches (ALTA) Group Study.

PURPOSE: To evaluate recovery of platelet count after transjugular intrahepatic portosystemic shunt (TIPS) creation and patient factors predicting platelet recovery after TIPS creation. MATERIALS AND METHODS: Adults with cirrhosis who underwent TIPS creation at 9 U.S. hospitals from 2010 to 2015 were included in this retrospective analysis. Change in platelets from before TIPS to 4 months after TIPS creation was characterized. Logistic regression was used to assess factors associated with top quartile percentage platelet increase after TIPS. Subgroup analyses were performed among patients with a pre-TIPS platelet count of ≤50 ×109/L. RESULTS: A total of 601 patients were included. The median absolute change in platelets was 1 × 109/L (-26 × 109/L to 25 × 109/L). Patients with top quartile percent platelet increase experienced ≥32% platelet increase. In multivariable analysis, pre-TIPS platelet counts (odds ratio [OR], 0.97 per 109/L; 95% CI, 0.97-0.98), age (OR, 1.24 per 5 years; 95% CI, 1.10-1.39), and pre-TIPS model for end-stage liver disease (MELD) scores (OR, 1.06 per point; 95% CI, 1.02-1.09) were associated with top quartile (≥32%) platelet increase. Ninety-four (16%) patients had a platelet count of ≤50 × 109/L before TIPS. The median absolute platelet change was 14 × 109/L (2 × 109/L to 34 × 109/L). Fifty-four percent of patients in this subgroup were in the top quartile for platelet increase. In multivariable logistic regression, age (OR, 1.50 per 5 years; 95% CI, 1.11-2.02) was the only factor associated with top quartile platelet increase in this subgroup. CONCLUSIONS: TIPS creation did not result in significant platelet increase, except among patients with a platelet count of ≤50 × 109/L before TIPS. Lower pre-TIPS platelet counts, older age, and higher pre-TIPS MELD scores were associated with top quartile (≥32%) platelet increase in the entire cohort, whereas only older age was associated with this outcome in the patient subset with a pre-TIPS platelet count of ≤50 × 109/L.

Impacts of neoadjuvant therapy on the number of dissected lymph nodes in esophagogastric junction cancer patients.

BACKGROUND: Neoadjuvant therapy favors the prognosis of various cancers, including esophagogastric junction cancer (EGC). However, the impacts of neoadjuvant therapy on the number of dissected lymph nodes (LNs) have not yet been evaluated in EGC. METHODS: We selected EGC patients from the Surveillance, Epidemiology, and End Results (SEER) database (2006-2017). The optimal number of resected LNs was determined using X-tile software. Overall survival (OS) curves were plotted with the Kaplan-Meier method. Prognostic factors were evaluated using univariate and multivariate COX regression analyses. RESULTS: Neoadjuvant radiotherapy significantly decreased the mean number of LN examination compared to the mean number of patients without neoadjuvant therapy (12.2 vs. 17.5, P = 0.003). The mean LN number of patients with neoadjuvant chemoradiotherapy was 16.3, which was also statistically lower than 17.5 (P = 0.001). In contrast, neoadjuvant chemotherapy caused a significant increase in the number of dissected LNs (21.0, P < 0.001). For patients with neoadjuvant chemotherapy, the optimal cutoff value was 19. Patients with > 19 LNs had a better prognosis than those with 1-19 LNs (P < 0.05). For patients with neoadjuvant chemoradiotherapy, the optimal cutoff value was 9. Patients with > 9 LNs had a better prognosis than those with 1-9 LNs (P < 0.05). CONCLUSIONS: Neoadjuvant radiotherapy and chemoradiotherapy decreased the number of dissected LNs, while neoadjuvant chemotherapy increased it in EGC patients. Hence, at least 10 LNs should be dissected for neoadjuvant chemoradiotherapy and 20 for neoadjuvant chemotherapy, which could be applied in clinical practice.

Based on the IWATE criteria: to investigate the influence of different surgical approaches on the perioperative outcomes of hepatectomy.

BACKGROUND: In terms of perioperative outcomes, compared with traditional open surgery and laparoscopic surgery, studies of robotic liver resection have been limited and must be further clarified. METHODS: Clinical data from 465 patients who underwent liver resection were collected in this retrospective study, and the IWATE criteria were used to evaluate the difficulty level of each operation. We compared perioperative outcomes of open, laparoscopic, or robotic approaches for patients with uncomplicated and complex hepatectomy according to different IWATE scores. Among patients with uncomplicated hepatectomy, the median operation time was significantly longer in the robotic liver resection (RLR) group than in the open liver resection (OLR) and laparoscopic liver resection (LLR) groups; however, the RLR group had the shortest hospital stay. There were no significant differences in intraoperative blood loss, conversion rate, total complication rate, or serious complication rate among the three groups. RESULTS: Among patients with complex hepatectomy, the RLR group had the smallest intraoperative blood loss and shortest mean length of stay. The cases converted to open hepatectomy were lower in the RLR group than in the laparoscopic group, mainly based on the IWATE score of expert hepatectomy. The incidence of general and serious postoperative complications in the RLR group was significantly lower than that in the OLR and LLR groups. CONCLUSIONS: Robotic liver resection is a safe and feasible surgical method that is more advantageous than laparoscopic and open liver resection, especially in complex liver surgery.

Empirical validation of the information-motivation-behavioral skills model of gestational weight management behavior: a framework for intervention.

BACKGROUND: Unhealthy gestational weight gain is a modifiable risk factor for adverse maternal and child health. Appropriate and effective intervention strategies that focus on behavioral change or maintenance are critical in weight management during pregnancy. Our aim was to uncover the influencing factors and psychosocial mechanisms of gestational weight control behavior, and to construct a behavioral model suitable for intervention based on Information-Motivation-Behavioral skills (IMB) model. METHODS: A sample of 559 pregnant women from a municipal maternal and child healthcare facility in Jiangsu Province, China was enrolled in this cross-sectional empirical study. Partial least square structural equation modelling was used to verify the hypothesized model, and post hoc analyses was used to test the effect of parity and pre-pregnancy BMI on the model. RESULTS: The IMB model elements can predict gestational weight management (GWM) behavior well, with information being the most influential factor. As predicted, information affects GWM directly (ß = 0.325, p < 0.05) and indirectly (ß = 0.054, p < 0.05) through behavioral skills. Likewise, motivation has direct (ß = 0.461, p < 0.05) effects on GWM, and has indirect (ß = 0.071, p < 0.05) effects through behavioral skills. Behavioral skills have a direct impact (ß = 0.154, p < 0.05). The model had a goodness of fit (GOF = 0.421) and was robust when tested in subgroups of different parity or pre-pregnancy BMI. CONCLUSION: Findings from this study supported the predictions of the IMB model for GWM behavior, and identified its modifiable determinants. The tested behavior model for GWM can serve as a new validated intervention strategy in weight management among pregnant women.