Immune checkpoint inhibitors and anti-vascular endothelial growth factor antibody/tyrosine kinase inhibitors with or without transarterial chemoembolization as first-line treatment for advanced hepatocellular carcinoma (CHANCE2201): a target trial emulation study.

Background: The role of transarterial chemoembolization (TACE) in the treatment of advanced hepatocellular carcinoma (HCC) is unconfirmed. This study aimed to assess the efficacy and safety of immune checkpoint inhibitors (ICIs) plus anti-vascular endothelial growth factor (anti-VEGF) antibody/tyrosine kinase inhibitors (TKIs) with or without TACE as first-line treatment for advanced HCC. Methods: This nationwide, multicenter, retrospective cohort study included advanced HCC patients receiving either TACE with ICIs plus anti-VEGF antibody/TKIs (TACE-ICI-VEGF) or only ICIs plus anti-VEGF antibody/TKIs (ICI-VEGF) from January 2018 to December 2022. The study design followed the target trial emulation framework with stabilized inverse probability of treatment weighting (sIPTW) to minimize biases. The primary outcome was overall survival (OS). Secondary outcomes included progression-free survival (PFS), objective response rate (ORR), and safety. The study is registered with ClinicalTrials.gov, NCT05332821. Findings: Among 1244 patients included in the analysis, 802 (64.5%) patients received TACE-ICI-VEGF treatment, and 442 (35.5%) patients received ICI-VEGF treatment. The median follow-up time was 21.1 months and 20.6 months, respectively. Post-application of sIPTW, baseline characteristics were well-balanced between the two groups. TACE-ICI-VEGF group exhibited a significantly improved median OS (22.6 months [95% CI: 21.2-23.9] vs 15.9 months [14.9-17.8]; P < 0.0001; adjusted hazard ratio [aHR] 0.63 [95% CI: 0.53-0.75]). Median PFS was also longer in TACE-ICI-VEGF group (9.9 months [9.1-10.6] vs 7.4 months [6.7-8.5]; P < 0.0001; aHR 0.74 [0.65-0.85]) per Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1. A higher ORR was observed in TACE-ICI-VEGF group, by either RECIST v1.1 or modified RECIST (41.2% vs 22.9%, P < 0.0001; 47.3% vs 29.7%, P < 0.0001). Grade ≥3 adverse events occurred in 178 patients (22.2%) in TACE-ICI-VEGF group and 80 patients (18.1%) in ICI-VEGF group. Interpretation: This multicenter study supports the use of TACE combined with ICIs and anti-VEGF antibody/TKIs as first-line treatment for advanced HCC, demonstrating an acceptable safety profile. Funding: National Natural Science Foundation of China, National Key Research and Development Program of China, Jiangsu Provincial Medical Innovation Center, Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, and Nanjing Life Health Science and Technology Project.

Neurological manifestations and risk factors associated with poor prognosis in hospitalized children with Omicron variant infection.

There are increasing reports of neurological manifestation in children with coronavirus disease 2019 (COVID-19). However, the frequency and clinical outcomes of in hospitalized children infected with the Omicron variant are unknown. The aim of this study was to describe the clinical characteristics, neurological manifestations, and risk factor associated with poor prognosis of hospitalized children suffering from COVID-19 due to the Omicron variant. Participants included children older than 28 days and younger than 18 years. Patients were recruited from December 10, 2022 through January 5, 2023. They were followed up for 30 days. A total of 509 pediatric patients hospitalized with the Omicron variant infection were recruited into the study. Among them, 167 (32.81%) patients had neurological manifestations. The most common manifestations were febrile convulsions (n = 90, 53.89%), viral encephalitis (n = 34, 20.36%), epilepsy (n = 23, 13.77%), hypoxic-ischemic encephalopathy (n = 9, 5.39%), and acute necrotizing encephalopathy (n = 6, 3.59%). At discharge, 92.81% of patients had a good prognosis according to the Glasgow Outcome Scale (scores ≥ 4). However, 7.19% had a poor prognosis. Eight patients died during the follow-up period with a cumulative 30-day mortality rate of 4.8% (95% confidence interval (CI) 1.5-8.1). Multivariate analysis revealed that albumin (odds ratio 0.711, 95% CI 0.556-0.910) and creatine kinase MB (CK-MB) levels (odds ratio 1.033, 95% CI 1.004-1.063) were independent risk factors of poor prognosis due to neurological manifestations. The area under the curve for the prediction of poor prognosis with albumin and CK-MB was 0.915 (95%CI 0.799-1.000), indicating that these factors can accurately predict a poor prognosis.          Conclusion: In this study, 32.8% of hospitalized children suffering from COVID-19 due to the Omicron variant infection experienced neurological manifestations. Baseline albumin and CK-MB levels could accurately predict poor prognosis in this patient population. What is Known: • Neurological injury has been reported in SARS-CoV-2 infection; compared with other strains, the Omicron strain is more likely to cause neurological manifestations in adults. • Neurologic injury in adults such as cerebral hemorrhage and epilepsy has been reported in patients with Omicron variant infection. What is New: • One-third hospitalized children with Omicron infection experience neurological manifestations, including central nervous system manifestations and peripheral nervous system manifestations. • Albumin and CK-MB combined can accurately predict poor prognosis (AUC 0.915), and the 30-day mortality rate of children with Omicron variant infection and neurological manifestations was 4.8%.

Reyanning mixture inhibits M1 macrophage polarization through the glycogen synthesis pathway to improve lipopolysaccharide-induced acute lung injury.

ETHNOPHARMACOLOGICAL RELEVANCE: Reyanning (RYN) mixture is a traditional Chinese medicine composed of Taraxacum, Polygonum cuspidatum, Scutellariae Barbatae and Patrinia villosa and is used for the treatment of acute respiratory system diseases with significant clinical efficacy. AIM OF THE STUDY: Acute lung injury (ALI) is a common clinical disease characterized by acute respiratory failure. This study was conducted to evaluate the therapeutic effects of RYN on ALI and to explore its mechanism of action. MATERIALS AND METHODS: Ultra-high-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was used to analyze the chemical components of RYN. 7.5 mg/kg LPS was administered to induce ALI in rats. RYN was administered by gavage at doses of 2 ml/kg, 4 ml/kg or 8 ml/kg every 8 h for a total of 6 doses. Observations included lung histomorphology, lung wet/dry (W/D) weight ratio, lung permeability index (LPI), HE staining, Wright-Giemsa staining. ELISA was performed to detect the levels of TNF-α, IL-6, IL-10, Arg-1,UDPG. Immunohistochemical staining detected IL-6, F4/80 expression. ROS, MDA, SOD, GSH/GSSG were detected in liver tissues. Multiple omics techniques were used to predict the potential mechanism of action of RYN, which was verified by in vivo closure experiments. Immunofluorescence staining detected the co-expression of CD86 and CD206, CD86 and P2Y14, CD86 and UGP2 in liver tissues. qRT-PCR detected the mRNA levels of UGP2, P2Y14 and STAT1, and immunoblotting detected the protein expression of UGP2, P2Y14, STAT1, p-STAT1. RESULTS: RYN was detected to contain 1366 metabolites, some of the metabolites with high levels have anti-inflammatory, antibacterial, antiviral and antioxidant properties. RYN (2, 4, and 8 ml/kg) exerted dose-dependent therapeutic effects on the ALI rats, by reducing inflammatory cell infiltration and oxidative stress damage, inhibiting CD86 expression, decreasing TNF-α and IL-6 levels, and increasing IL-10 and Arg-1 levels. Transcriptomics and proteomics showed that glucose metabolism provided the pathway for the anti-ALI properties of RYN and that RYN inhibited lung glycogen production and distribution. Immunofluorescence co-staining showed that RYN inhibited CD86 and UGP2 expressions. In vivo blocking experiments revealed that blocking glycogen synthesis reduced UDPG content, inhibited P2Y14 and CD86 expressions, decreased P2Y14 and STAT1 mRNA and protein expressions, reduced STAT1 protein phosphorylation expression, and had the same therapeutic effect as RYN. CONCLUSION: RYN inhibits M1 macrophage polarization to alleviate ALI. Blocking glycogen synthesis and inhibiting the UDPG/P2Y14/STAT1 signaling pathway may be its molecular mechanism.

Superbinder based phosphoproteomic landscape revealed PRKCD_pY313 mediates the activation of Src and p38 MAPK to promote TNBC progression.

Phosphorylation proteomics is the basis for the study of abnormally activated kinase signaling pathways in breast cancer, which facilitates the discovery of new oncogenic agents and drives the discovery of potential targets for early diagnosis and therapy of breast cancer. In this study, we have explored the aberrantly active kinases in breast cancer development and to elucidate the role of PRKCD_pY313 in triple negative breast cancer (TNBC) progression. We collected 47 pairs of breast cancer and paired far-cancer normal tissues and analyzed phosphorylated tyrosine (pY) peptides by Superbinder resin and further enriched the phosphorylated serine/threonine (pS/pT) peptides using TiO2 columns. We mapped the kinases activity of different subtypes of breast cancer and identified PRKCD_pY313 was upregulated in TNBC cell lines. Gain-of-function assay revealed that PRKCD_pY313 facilitated the proliferation, enhanced invasion, accelerated metastasis, increased the mitochondrial membrane potential and reduced ROS level of TNBC cell lines, while Y313F mutation and low PRKCD_pY313 reversed these effects. Furthermore, PRKCD_pY313 significantly upregulated Src_pY419 and p38_pT180/pY182, while low PRKCD_pY313 and PRKCD_Y313F had opposite effects. Dasatinib significantly inhibited the growth of PRKCD_pY313 overexpression cells, and this effect could be enhanced by Adezmapimod. In nude mice xenograft model, PRKCD_pY313 significantly promoted tumor progression, accompanied by increased levels of Ki-67, Bcl-xl and Vimentin, and decreased levels of Bad, cleaved caspase 3 and ZO1, which was opposite to the trend of Y313F group. Collectively, the heterogeneity of phosphorylation exists in different molecular subtypes of breast cancer. PRKCD_pY313 activates Src and accelerates TNBC progression, which could be inhibited by Dasatinib.

Trends in gynaecologic cancer mortality and the impact of the COVID-19 pandemic in the United States.

OBJECTIVES: Our aim was to assess the trend in gynaecologic cancer (GC) mortality in the period from 2010 to 2022 in the United States, with focus on the impact of the pandemic on increased deaths. METHODS: GC mortality data were extracted from the Center for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research (CDC WONDER) platform. We analysed mortality trends and evaluated observed vs. predicted mortality for the period from 2020 to 2022 with joinpoint regression and prediction modelling analyses. RESULTS: A total of 334,382 deaths among adults aged 25 years and older with gynaecologic cancer were documented from 2010 to 2022. The overall age-standardised mortality rate (ASMR, per 100,000 persons) for ovarian cancer-related death decreased gradually from 7.189 in 2010 to 5.517 in 2019, yielding an APC (annual percentage change) of -2.8%. However, the decrease in ovarian cancer-related mortality slowed down by more than 4-fold during the pandemic. Cervical cancer -related mortality decreased slightly prior to the pandemic and increased during the pandemic with an APC of 0.6%, resulting in excess mortality of 4.92%, 9.73% and 2.03% in 2020, 2021 and 2022, respectively. For uterine corpus cancer, the ASMR increased from 1.905 in 2010 to 2.787 in 2019, and increased sharply to 3.079 in 2021 and 3.211 in 2022. The ASMR rose steadily between 2013 and 2022, yielding an APC of 6.9%. CONCLUSIONS: Overall, we found that GC-related mortality increased during the COVID-19 pandemic, and this increase was not specific to age, race, or ethnicity.

Machine learning versus multivariate logistic regression for predicting severe COVID-19 in hospitalized children with Omicron variant infection.

With the emergence of the Omicron variant, the number of pediatric Coronavirus Disease 2019 (COVID-19) cases requiring hospitalization and developing severe or critical illness has significantly increased. Machine learning and multivariate logistic regression analysis were used to predict risk factors and develop prognostic models for severe COVID-19 in hospitalized children with the Omicron variant in this study. Of the 544 hospitalized children including 243 and 301 in the mild and severe groups, respectively. Fever (92.3%) was the most common symptom, followed by cough (79.4%), convulsions (36.8%), and vomiting (23.2%). The multivariate logistic regression analysis showed that age (1-3 years old, odds ratio (OR): 3.193, 95% confidence interval (CI): 1.778-5.733], comorbidity (OR: 1.993, 95% CI:1.154-3.443), cough (OR: 0.409, 95% CI:0.236-0.709), and baseline neutrophil-to-lymphocyte ratio (OR: 1.108, 95% CI: 1.023-1.200), lactate dehydrogenase (OR: 1.993, 95% CI: 1.154-3.443), blood urea nitrogen (OR: 1.002, 95% CI: 1.000-1.003) and total bilirubin (OR: 1.178, 95% CI: 1.005-3.381) were independent risk factors for severe COVID-19. The area under the curve (AUC) of the prediction models constructed by multivariate logistic regression analysis and machine learning (RandomForest + TomekLinks) were 0.7770 and 0.8590, respectively. The top 10 most important variables of random forest variables were selected to build a prediction model, with an AUC of 0.8210. Compared with multivariate logistic regression, machine learning models could more accurately predict severe COVID-19 in children with Omicron variant infection.

Global incidence of adverse clinical events in non-alcoholic fatty liver disease: A systematic review and meta-analysis.

BACKGROUND/AIMS: Nonalcoholic fatty liver disease (NAFLD) is associated with a multitude of adverse outcomes. We aimed to estimate the pooled incidence of NAFLD-related adverse events. METHODS: We performed a systematic review and meta-analysis of cohort studies of adults with NAFLD to evaluate the pooled incidence of adverse events. RESULTS: 19,406 articles were screened, 409 full-text articles reviewed, and 79 eligible studies (1,377,466 persons) were included. Mean age was 51.47 years and body mass index 28.90 kg/m2. Baseline comorbidities included metabolic syndrome (41.73%), cardiovascular disease (CVD) (16.83%), cirrhosis (21.97%), and nonalcoholic steatohepatitis (NASH) (58.85%). Incidence rate per 1,000 person-years for mortality included: all-cause (14.6), CVD-related (4.53), non-liver cancer-related (4.53), and liver-related (3.10). Incidence for liver-related events included overall (24.3), fibrosis progression (49.0), cirrhosis (10.9), liver transplant (12.0), and hepatocellular carcinoma (HCC) (3.39). Incidence for non-liver events included metabolic syndrome (25.4), hypertension (25.8), dyslipidemia (26.4), diabetes (19.0), CVD (24.77), renal impairment (30.3), depression/anxiety (29.1), and non-liver cancer (10.5). Biopsy-proven NASH had higher incidence of HCC (P=0.043) compared to non-NASH. Higher rates of CVD and mortality were observed in North America and Europe, hypertension and non-liver cancer in North America, and HCC in Western Pacific/Southeast Asia (P<0.05). No significant differences were observed by sex. Time-period analyses showed decreasing rates of cardiovascular and non-liver cancer mortality and increasing rates of decompensated cirrhosis (P<0.05). CONCLUSION: People with NAFLD have high incidence of liver and non-liver adverse clinical events, varying by NASH, geographic region, and time-period, but not sex.

Prevalence of and associated factors for sarcopenia in patients with liver cirrhosis: A systematic review and meta-analysis.

BACKGROUND: Sarcopenia is associated with poor outcomes in patients with cirrhosis. However, the prevalence of and associated factors for developing sarcopenia in this population remain to be determined. OBJECTIVES: This study aimed to summarize the prevalence, characteristics, and associated factors of sarcopenia in patients with cirrhosis. METHODS: Electronic searches were performed from inception to June 9, 2022 to identify the eligible studies. We meta-analyzed the prevalence of sarcopenia in overall patients with cirrhosis and subgroups. Both crude and adjusted odds ratios (ORs) were pooled using the random effects model. RESULTS: A total of 55 studies involving 13,158 patients from 17 countries were included. The overall prevalence of sarcopenia was 40.1 % (95 % CI 35.4%-44.9 %) in patients with cirrhosis. The pooled prevalence was higher in males, Child-Pugh class C cirrhosis, decompensated stage, ascites, subjective global assessment class C cirrhosis, and when sarcopenia was defined by L3-SMI (third lumbar-skeletal muscle index) at a higher cutoff. In multivariate analysis, older age (adjusted OR 1.04, 95 % CI 1.00-1.07), male (adjusted OR 4.75, 95 % CI 2.72-8.28), lower body mass index (BMI) (adjusted OR 0.78, 95 % CI 0.73-0.83), alcoholic liver disease (ALD) (adjusted OR 1.43, 95 % CI 1.19-1.72), but not ascites and hepatic encephalopathy, were significantly associated with an increased risk of sarcopenia in patients with cirrhosis. CONCLUSION: Sarcopenia is a prevalent complication, and older age, male patients, lower BMI, and patients with ALD are associated with an increased risk of sarcopenia in patients with cirrhosis.

Treatment rates and factors associated with direct-acting antiviral therapy for insured patients with hepatitis C-related hepatocellular carcinoma - A real-world nationwide study.

BACKGROUND: Since the inception of the interferon-free direct-acting antiviral agents (DAAs) for hepatitis C virus (HCV) infection, guidelines as to who should receive this potentially curative treatment have evolved. Treatment with DAAs is now considered for all patients except for those considered moribund. AIM: To determine the DAA treatment rate for patients with HCV-related hepatocellular carcinoma (HCC). METHODS: This was a retrospective study from January 2015 to March 2021 of a national sample of privately insured patients with HCV-related HCC using Optum's Clinformatics® Data Mart (CDM) Database - a large, de-identified, adjudicated claims database. RESULTS: We identified 3922 patients with HCV-related HCC: 922 (23.5%) received DAA. Compared to untreated patients, DAA-treated patients were younger (65.2 ± 7.5 vs. 66.4 ± 7.5 years, p < 0.001), more frequently saw a gastroenterology/infectious disease (GI/ID) physician (41.2% vs. 34.2%), and had decompensated cirrhosis (56% vs. 53%, p = 0.001). In multivariable analysis, younger age (HR: 0.98, 95% CI: 0.97-0.99, p < 0.001), GI/ID care (HR: 3.06, 95% CI: 2.13-4.51, p < 0.001), and having cirrhosis (compensated: HR: 1.60, 95% CI: 1.18-2.21, p = 0.003; decompensated: HR: 1.45, 95% CI: 1.07-1.98, p = 0.02) were associated with receiving DAA treatment, but not sex, race, or ethnicity. DAA-treated patients had significantly higher 5-year survival than untreated patients (47.2% vs. 35.2%, p < 0.001). Following adjustment for age, sex, race/ethnicity, Charlson Comorbidity Index, and HCC treatment, receiving DAA treatment was associated with lower mortality (aHR: 0.61, 95% CI: 0.53-0.69, p < 0.001). CONCLUSION: DAA treatment remains underutilised in insured patients with HCV-related HCC; fewer than one in four patients received treatment. Seeing a specialist and having decompensated cirrhosis were predictors for DAA treatment; additional efforts are needed to increase awareness of HCV treatment.

Immune Checkpoint Inhibitors for Child-Pugh Class B Advanced Hepatocellular Carcinoma: A Systematic Review and Meta-Analysis.

Importance: Immune checkpoint inhibitors (ICIs) are increasingly used in patients with advanced hepatocellular carcinoma (HCC). However, data on ICI therapy in patients with advanced HCC and impaired liver function are scarce. Objective: To conduct a systematic review and meta-analysis to determine the efficacy and safety of ICI treatment for advanced HCC with Child-Pugh B liver function. Data Sources: PubMed, Embase, Web of Science, and Cochrane Library were searched for relevant studies from inception through June 15, 2022. Study Selection: Randomized clinical trials, cohort studies, or single-group studies that investigated the efficacy or safety of ICI therapy for Child-Pugh B advanced HCC were included. Data Extraction and Synthesis: The Preferred Reporting Items for Systematic Reviews and Meta-Analysis guideline was followed to extract data. A random-effects model was adopted if the heterogeneity was significant (I2 > 50%); otherwise, a fixed-effect model was used. Main Outcomes and Measures: The objective response rate (ORR) and overall survival (OS) were considered to be the primary efficacy outcomes of ICI treatment for Child-Pugh B advanced HCC, and the incidence of treatment-related adverse events (trAEs) was set as the primary measure for the safety outcome. Results: A total of 22 studies including 699 patients with Child-Pugh B and 2114 with Child-Pugh A advanced HCC comprised the analytic sample (median age range, 53-73 years). Upon pooled analysis, patients treated with ICIs in the Child-Pugh B group had an ORR of 14% (95% CI, 11%-17%) and disease control rate (DCR) of 46% (95% CI, 36%-56%), with a median OS of 5.49 (95% CI, 3.57-7.42) months and median progression-free survival of 2.68 (95% CI, 1.85-3.52) months. The rate of any grade trAEs in the Child-Pugh B group was 40% (95% CI, 34%-47%) and of grade 3 or higher trAEs was 12% (95% CI, 6%-23%). Compared with the Child-Pugh A group, the ORR (odds ratio, 0.59; 95% CI, 0.43-0.81; P < .001) and DCR (odds ratio, 0.64; 95% CI, 0.50-0.81; P < .001) were lower in the Child-Pugh B group. Child-Pugh B was independently associated with worse OS in patients with advanced HCC treated with ICIs (hazard ratio, 2.72 [95% CI, 2.34-3.16]; adjusted hazard ratio, 2.33 [95% CI, 1.81-2.99]). However, ICIs were not associated with increased trAEs in the Child-Pugh B group. Conclusions and Relevance: The findings of this systematic review and meta-analysis suggest that although the safety of ICI treatment was comparable between patients with HCC with vs without advanced liver disease and the treatment resulted in a significant number of radiologic responses, survival outcomes are still inferior in patients with worse liver function. More study is needed to determine the effectiveness of ICI treatment in this population.

Shared-care models are highly effective and cost-effective for managing chronic hepatitis B in China: reinterpreting the primary care and specialty divide.

Background: We evaluate the impact and cost-effectiveness of shared primary-specialty chronic hepatitis B (CHB) care models in China. Methods: We constructed a decision-tree Markov model to simulate hepatitis B virus (HBV) disease progression in a cohort of 100,000 CHB individuals aged ≥18 years over their lifetime (aged 80). We evaluated the population impacts and cost-effectiveness in three scenarios: (1) status quo; (2) shared-care model with HBV testing and routine CHB follow-ups in primary care and antiviral treatment initiation in specialty care; and (3) shared-care model with HBV testing, treatment initiation and routine CHB follow-up in primary care and treatment for predetermined conditions in specialty care. We evaluated from a healthcare provider's perspective with 3% discounting rate and a willingness-to-pay (WTP) threshold of 1-time China's GDP. Findings: Compared with status quo, scenario 2 would result in an incremental cost of US$5.79-132.43m but a net gain of 328-16,993 quality-adjusted life years (QALYs) and prevention of 39-1935 HBV-related deaths over cohort's lifetime. Scenario 2 was not cost-effective with a WTP of 1-time GDP per capita, but became cost-effective when treatment initiation rate increased to 70%. In contrast, compared with status quo, secnario 3 would save US$144.59-192.93m in investment and achieve a net gain of 23,814-30,476 QALYs and prevention of 3074-3802 HBV-related deaths. Improving HBV antiviral treatment initiation among eligible CHB individuals substantially improved the cost-effectiveness of the shared-care models. Interpretation: Shared-care models with HBV testing, follow up and referring of predetermined conditions to specialty care at an appropriate time, especially antiviral treatment initiation in primary care, are highly effective and cost-effective in China. Funding: National Natural Science Foundation of China.

Real-world treatment outcome with protease inhibitor direct-acting antiviral in advanced hepatitis C cirrhosis: a REAL-C study.

INTRODUCTION: Current guidelines discourage the use of direct-acting antiviral (DAA) containing protease-inhibitor (PI) in advanced HCV cirrhosis. We aimed to compare the real-world tolerability of PI vs. non-PI DAA regimens in this population. METHODS: We identified advanced cirrhosis patients treated with DAA from the REAL-C registry. The primary outcome was significant worsening or improvement in CPT or MELD scores following DAA treatment. RESULTS: From the REAL-C registry of 15,837 patients, we included 1077 advanced HCV cirrhosis patients from 27 sites. 42% received PI-based DAA. Compared to non-PI group, the PI group was older, had higher MELD and higher percentage with kidney disease. Inverse probability of treatment weighting (IPTW; matching on age, sex, history of clinical decompensation, MELD, platelet, albumin, Asia site, Asian ethnicity, hypertension, hemoglobin, genotype, liver cancer, ribavirin) was used to balance the two groups. In the IPTW-matched cohorts, the PI and non-PI groups had similar SVR12 (92.9% vs. 90.7%, p = 0.30), similar percentages of significant worsening in CTP or MELD scores at posttreatment week 12 and 24 (23.9% vs. 13.1%, p = 0.07 and 16.5% vs. 14.6%, p = 0.77), and similar frequency of new HCC, decompensating event, and death by posttreatment week 24. In multivariable analysis, PI-based DAA was not associated with significant worsening (adjusted odds ratio = 0.82, 95% CI 0.38-1.77). CONCLUSION: Tolerability and treatment outcomes were not significantly different in advanced HCV cirrhosis treated with PI-based (vs. non-PI) DAA up to CTP-B or MELD score of 15. Safety of PI-based DAA in those with CTP-C or MELD beyond 15 awaits further data.

[Prevalence Survey of Functional Dyspepsia and Irritable Bowel Syndrome in Chinese College Students Based on Rome â £ Diagnostic Criteria].

Objective: To investigate the prevalence and risk factors of functional dyspepsia (FD) and irritable bowel syndrome (IBS) among college students in China. Methods: An online questionnaire survey of college students aged 17-35 from across China was conducted. The online questionnaire survey was supplemented by an offline survey. A total of 2025 valid samples were included for statistical analysis. χ 2 test and logistic regression were performed for statistical analysis. Results: The prevalence of FD among college students who met the Rome Ⅳ diagnostic criteria was 5.5% (112/2025), with most of them, or 66.1% (74/112), suffering from postprandial discomfort syndrome (PDS). Smoking (odds ratio [ OR]=2.334, 95% confidence interval [ CI]: 1.187-4.589, P=0.014), depression ( OR=2.447, 95% CI: 1.421-4.214, P=0.001), and insomnia ( OR=1.947, 95% CI: 1.291-2.937, P=0.001) were positively correlated with the prevalence of FD. The prevalence of IBS was 1.9% (38/2025), with IBS-diarrhea dominant (IBS-D) being the most important subtype that accounted for 44.7%. Anxiety ( OR=3.63, 95% CI: 1.34-9.88, P=0.012) and insomnia ( OR=2.35, 95% CI: 1.18-4.68, P=0.015) were positively correlated with the prevalence of IBS. Conclusion: Based on Rome Ⅳ criteria, IBS and FD are not uncommon among Chinese university students. Psychological disorders and some related lifestyle factors may be related to the development of the disease. In the future, more series of studies based on different diagnostic criteria, different regions, and multiple factors should be conducted in China.

Sarcopenia in cirrhosis: epidemiology, diagnosis, management and prognosis.

PURPOSE OF REVIEW: With the development of many international guidelines, research on sarcopenia has increased rapidly, showing that sarcopenia is predictive of adverse outcomes, including increased mortality and impaired mobility, in patients with cirrhosis. The purpose of this article is to review the current evidence concerning the epidemiology, diagnosis, management and predictive value of sarcopenia on the prognosis of patients with cirrhosis. RECENT FINDINGS: Sarcopenia is a frequent and lethal complication of cirrhosis. Currently, abdominal computed tomography imaging is the most commonly used method to diagnose sarcopenia. In clinical practice, assessing muscle strength and physical performance, such as by measuring handgrip strength and gait speed, is of increasing interest. In addition to the necessary pharmacological therapy, adequate intake of protein, energy and micronutrients, as well as regular moderate-intensity exercise, can help to minimize sarcopenia. Sarcopenia has been shown to be a strong predictor of prognosis in patients with severe liver disease. SUMMARY: A global consensus is needed on the definition and operational parameters for the diagnosis of sarcopenia. Further research should focus on developing standardized screening, management and treatment protocols for sarcopenia. Adding sarcopenia to existing models may better exploit the effect of sarcopenia on prognosis in patients with cirrhosis, which should be investigated further.

Associations of psychological wellbeing with COVID-19 hospitalization and mortality in adults aged 50 years or older from 25 European countries and Israel.

Background: Lower psychological wellbeing is associated with poor outcomes in a variety of diseases and healthy populations. However, no study has investigated whether psychological wellbeing is associated with the outcomes of COVID-19. This study aimed to determine whether individuals with lower psychological wellbeing are more at risk for poor outcomes of COVID-19. Methods: Data were from the Survey of Health, Aging, and Retirement in Europe (SHARE) in 2017 and SHARE's two COVID-19 surveys in June-September 2020 and June-August 2021. Psychological wellbeing was measured using the CASP-12 scale in 2017. The associations of the CASP-12 score with COVID-19 hospitalization and mortality were assessed using logistic models adjusted for age, sex, body mass index, smoking, physical activity, household income, education level, and chronic conditions. Sensitivity analyses were performed by imputing missing data or excluding cases whose diagnosis of COVID-19 was solely based on symptoms. A confirmatory analysis was conducted using data from the English Longitudinal Study of Aging (ELSA). Data analysis took place in October 2022. Results: In total, 3,886 individuals of 50 years of age or older with COVID-19 were included from 25 European countries and Israel, with 580 hospitalized (14.9%) and 100 deaths (2.6%). Compared with individuals in tertile 3 (highest) of the CASP-12 score, the adjusted odds ratios (ORs) of COVID-19 hospitalization were 1.81 (95% CI, 1.41-2.31) for those in tertile 1 (lowest) and 1.37 (95% CI, 1.07-1.75) for those in tertile 2. As for COVID-19 mortality, the adjusted ORs were 2.05 (95% CI, 1.12-3.77) for tertile 1 and 1.78 (95% CI, 0.98-3.23) for tertile 2, compared with tertile 3. The results were relatively robust to missing data or the exclusion of cases solely based on symptoms. This inverse association of the CASP-12 score with COVID-19 hospitalization risk was also observed in ELSA. Conclusion: This study shows that lower psychological wellbeing is independently associated with increased risks of COVID-19 hospitalization and mortality in European adults aged 50 years or older. Further study is needed to validate these associations in recent and future waves of the COVID-19 pandemic and other populations.

HIV-related mortality in the United States during the COVID-19 pandemic: A population-based study.

BACKGROUND: US progress toward ending the HIV epidemic was disrupted during the COVID-19 pandemic. OBJECTIVES: To determine the impact of the pandemic on HIV-related mortality and potential disparities. METHODS: Using data from the Centers for Disease Control and Prevention and the United States (US) Census Bureau, HIV-related mortality data of decedents aged ≥25 years between 2012 and 2021 were analyzed. Excess HIV-related mortality rates were estimated by determining the difference between observed and projected mortality rates during the pandemic. The trends of mortality were quantified with joinpoint regression analysis. RESULTS: Of the 79,725 deaths documented in adults aged 25 years and older between 2012 and 2021, a significant downward trend was noted in HIV-related mortality rates before the pandemic, followed by a surge during the pandemic. The observed mortality rates were 18.8% (95% confidence interval [CI]: 13.1%-25.5%) and 25.4% (95%CI: 19.9%-30.4%) higher than the projected values in 2020 and 2021, respectively. Both of these percentages were higher than that in the general population in 2020 (16.4%, 95%CI: 14.9%-17.9%) and 2021 (19.8%, 95%CI: 18.0%-21.6%), respectively. Increased HIV-related mortality was observed across all age subgroups, but those aged 25-44 years demonstrated the greatest relative increase and the lowest COVID-19-related deaths when compared to middle- and old-aged decedents. Disparities were observed across racial/ethnic subgroups and geographic regions. CONCLUSIONS: The pandemic led to a reversal in the attainments made to reduce the prevalence of HIV. Individuals living with HIV were disproportionately affected during the pandemic. Thoughtful policies are needed to address the disparity in excess HIV-related mortality.

Trends of Cirrhosis-related Mortality in the USA during the COVID-19 Pandemic.

Immunocompromised status and interrupted routine care may render patients with cirrhosis vulnerable to the coronavirus disease 2019 (COVID-19) pandemic. A nationwide dataset that includes more than 99% of the decedents in the U.S. between April 2012 and September 2021 was used. Projected age-standardized mortality during the pandemic were estimated according to prepandemic mortality rates, stratified by season. Excess deaths were determined by estimating the difference between observed and projected mortality rates. A temporal trend analysis of observed mortality rates was also performed in 0.83 million decedents with cirrhosis between April 2012 and September 2021 was included. Following an increasing trend of cirrhosis-related mortality before the pandemic, with a semiannual percentage change (SAPC) of 0.54% [95% confidence interval (CI): (0.0-1.0%), p=0.036], a precipitous increase with seasonal variation occurred during the pandemic (SAPC 5.35, 95% CI: 1.9-8.9, p=0.005). Significantly increased mortality rates were observed in those with alcohol-associated liver disease (ALD), with a SAPC of 8.44 (95% CI: 4.3-12.8, p=0.001) during the pandemic. All-cause mortality of nonalcoholic fatty liver disease rose steadily across the entire study period with a SAPC of 6.79 (95% CI: 6.3-7.3, p<0.001). The decreasing trend of HCV-related mortality was reversed during the pandemic, while there was no significant change in HBV-related deaths. While there was significant increase in COVID-19-related deaths, more than 55% of the excess deaths were the indirect impact of the pandemic. We observed an alarming increase in cirrhosis-related deaths during the pandemic especially for ALD, with evidence in both direct and indirect impact. Our findings have implications on formulating policies for patients with cirrhosis.