Prevalence of Steatotic Liver Disease Among US Adults with Rheumatoid Arthritis.

BACKGROUND: The prevalence of steatotic liver disease (SLD) among patients with rheumatoid arthritis (RA) remains largely unknown. AIMS: To investigate the prevalence of SLD and liver fibrosis among patients with RA. METHODS: We utilized data from the United States (US)-based National Health and Nutrition Examination Survey (NHANES) 2017-2020 cycle. After applying established sample weights, we estimated the age-adjusted prevalence of SLD and its subclassifications (CAP ≥ 285 dB/m), high-risk NASH (FAST score) and liver fibrosis (LSM) among participants with self-reported RA. Multivariable logistic regression was performed to identify independent risk factors for metabolic dysfunction associated SLD (MASLD), high-risk NASH and fibrosis, respectively, among participants with RA. We present adjusted odds ratios (aORs) and 95% confidence intervals (CIs). RESULTS: Age-adjusted prevalence of MASLD among US adults with RA was 34.91% (95% CI: 24.02-47.65%). We also found that the age-adjusted prevalence of high-risk NASH (FAST score > 0.35) and significant fibrosis (LSM > 8.6 kPa) was 12.97% (95% CI: 6.89-23.07%) and 10.35% (95% CI: 5.55-18.48%), respectively. BMI ≥ 30 kg/m2, (aOR 6.23; 95% CI: 1.95-19.88), diabetes (aOR 5.90; 95% CI: 1.94-17.94), and dyslipidemia (aOR 2.83; 95% CI: 1.12-7.11) were independently associated with higher odds of MASLD among participants with RA. Diabetes (aOR 19.34; 95% CI: 4.69-79.70) was also independently associated with high-risk NASH. CONCLUSIONS: The prevalence of MASLD, high-risk NASH, and liver fibrosis among patients with RA is equal or higher than the general population. Future studies of large cohorts are needed to substantiate the role of systemic inflammation in the pathophysiology of MASLD.

Prevalence of Steatotic Liver Disease (MASLD, MetALD, and ALD) in the United States: NHANES 2017-2020.

Following the Delphi consensus process, the term steatotic liver disease (SLD) was introduced to replace fatty liver disease, while the term metabolic dysfunction-associated steatotic liver disease (MASLD) emerged as the successor to the term nonalcoholic fatty liver disease (NAFLD).1 This revised nomenclature aims to enhance precision and mitigate negative connotations and potential stigmatization, while refining comprehension and disease categorization. Concurrently, a novel category was introduced to capture individuals whose alcohol consumption exceeded the previously defined thresholds of NAFLD but remained unclassified within the existing system. This category, termed MetALD, now delineates a spectrum of conditions and is defined as a daily intake of 20 to 50 g of alcohol (or weekly 140-350 g) for females and 30 to 60 g daily for males (or weekly 210-420 g).1 Within the MetALD spectrum, some individuals might predominantly exhibit MASLD characteristics, whereas others might be more inclined toward alcoholic liver disease (ALD).1 In the present study, we used a US nationally representative data set to calculate the prevalence of SLD and its subcategories in the United States.

Prevalence and Characteristics of Nonalcoholic Fatty Liver Disease and Fibrosis in People Living With HIV Monoinfection: A Systematic Review and Meta-analysis.

BACKGROUND AND AIMS: Liver disease remains a leading cause of morbidity and mortality among people living with HIV (PLWH). Emerging data suggest that PLWH are at high risk for developing nonalcoholic fatty liver disease (NAFLD). The aim of this review is to examine the current literature and provide an accurate estimate of the prevalence of NAFLD, nonalcoholic steatohepatitis (NASH), and fibrosis, and identify potential risk factors for NAFLD in PLWH. METHODS: We searched PubMed and Embase databases to identify studies reporting the prevalence of NAFLD and/or fibrosis in PLWH monoinfection. We performed a random effects meta-analysis of proportions to estimate the pooled prevalence of NAFLD, NASH, and fibrosis among PLWH monoinfection. We also examined potential risk factors for NAFLD by comparing characteristics of PLWH monoinfection with and without NAFLD. RESULTS: A total of 43 studies, reporting data for 8230 patients, met our eligibility criteria and were included in the meta-analysis. Based on imaging studies the overall pooled prevalence of NAFLD and moderate liver fibrosis (METAVIR ≥ F2) among PLWH monoinfection was 33.9% (95% confidence interval [CI], 29.67%-38.39%), and 12.00% (95% CI, 10.02%-14.12%), respectively. Based on biopsy studies, prevalence of NASH and significant liver fibrosis (stage ≥F2 on histology) was 48.77% (95% CI, 34.30%-63.34%) and 23.34% (95% CI, 14.98%-32.75%), respectively. Traditional metabolic syndrome and HIV-related factors were associated with NAFLD in PLWH. CONCLUSIONS: Our study confirms that the burden of NAFLD, NASH, and fibrosis is high among PLWH monoinfection. Prospective longitudinal studies are needed to delineate NAFLD, NASH, and fibrosis risk factors, and identify early interventions and new therapies for NAFLD in this population.

Impact of prior HBV, HAV, and HEV infection on non-alcoholic fatty liver disease.

Non-alcoholic fatty liver disease (NAFLD) is a leading cause of chronic liver disease. The association between prior hepatitis B virus (HBV), hepatitis A virus (HAV), hepatitis E virus (HEV) infection and NAFLD remains unclear. We utilized the 2017-2020 National Health and Nutrition Examination Survey (NHANES) and performed multivariable logistic regression analyses to examine the association of prior HBV, HAV and HEV infection with NAFLD, as well as high risk non-alcoholic steatohepatitis (NASH) and liver fibrosis. Our analysis included 2565 participants with available anti-HBc serology results, 1480 unvaccinated participants with anti-HAV results, and 2561 participants with anti-HEV results. Among participants with NAFLD, the age-adjusted prevalence of prior HBV, HAV and HEV infection was 3.48%, 32.08% and 7.45%, respectively. Prior infection with HBV, HAV and HEV was not associated with NAFLD (cut-off 285 dB/m) [aOR: 0.99 (95% CI, 0.77-1.29), 1.29 (95% CI, 0.95-1.75), and 0.94 (95% CI, 0.70-1.27), respectively] or high-risk NASH [aOR 0.72 (95% CI, 0.45-1.17), 0.92 (95% CI, 0.55-1.52), and 0.89 (95% CI, 0.41-1.94), respectively]. Participants with anti-HBc and anti-HAV seropositivity were more likely to have significant fibrosis [aOR: 1.53 (95% CI, 1.05-2.23) and 1.69 (95% CI, 1.16-2.47), respectively]. The odds of significant fibrosis are 53%, and 69% greater for participants with prior history of HBV and HAV infection. Healthcare providers should prioritize vaccination efforts and employ a tailored approach to NAFLD in patients with prior viral hepatitis and especially HBV or HAV infection to limit disease-related outcomes.

Outcomes of endoscopic retrograde cholangiopancreatography in patients with inflammatory bowel disease: a nationwide study.

PURPOSE: Endoscopic retrograde cholangiopancreatography (ERCP) has become a commonly utilized procedure for both diagnostic and therapeutic purposes. There is a paucity of data for patients with inflammatory bowel disease (IBD) who undergo ERCP. The aim of this study is to examine the indications, complications, and inpatient outcomes of patients with IBD undergoing ERCP. METHODS: For this retrospective cohort study, we utilized the National Inpatient Sample database for the years 2018-2019. We compared potential indications, outcomes, ERCP-related procedures, and resource utilization in patients who underwent ERCP and had a diagnosis of IBD to that of patients who underwent ERCP without a diagnosis of IBD. We utilized a multivariate regression model that accounted for several potential confounders. RESULTS: We identified 318,590 ERCP procedures. Among them, 3625 ERCP procedures were performed in patients with an associated diagnosis of IBD. Patients with IBD who underwent ERCP had higher odds of acute kidney injury (aOR 1.27; 95% CI: 1.01-1.60) and sepsis (aOR 1.33; 95% CI: 1.07-1.67) compared to patients without IBD. However, inpatient mortality and other complications were not statistically different between the two groups. Patients with IBD were also less likely to undergo biliary sphincterotomy (aOR 0.75; 95% CI: 0.62-0.88) but there were no other differences in performance of ERCP-related therapeutic interventions between the two groups. Adjusted costs and charges were not statistically different between the two groups. CONCLUSION: Our study shows that ERCP is, overall, a safe procedure in patients with IBD, as inpatient morbidity and mortality are similar to patients without IBD.

Antiproliferative Effect of Above-Label Doses of Somatostatin Analogs for the Management of Gastroenteropancreatic Neuroendocrine Tumors.

BACKGROUND: Above-label doses of somatostatin analogs (SSAs) are increasingly utilized in the management of inoperable/metastatic gastroenteropancreatic neuroendocrine tumors (GEP-NETs), progressing on standard 4-weekly regimens. OBJECTIVE: To evaluate the antiproliferative effect of 3-weekly SSA administration in a retrospective GEP-NET cohort. METHODS: Patients with advanced GEP-NET, treated with long-acting release (LAR) octreotide 30 mg or lanreotide Autogel 120 mg at a 3-weekly interval, after disease progression on standard 4-weekly doses, were retrospectively identified. Clinicopathologic and treatment response data were collected. Progression-free survival (PFS; dose escalation to radiographic progression or death) was estimated with the Kaplan-Meier method. Factors associated with PFS were identified with the Cox proportional-hazards model. RESULTS: The inclusion criteria were fulfilled by 105 patients. Octreotide LAR was administered to 60 (57%) and lanreotide Autogel to 45 (43%). Indications for dose escalation were breakthrough carcinoid symptoms (58%), radiographic progression (35%) and/or increasing biomarkers (11%). Diarrheal and/or flushing symptomatic improvement was identified in 37/67 cases (55%) and 30/55 cases (55%) with available data, respectively. The disease control rate (radiographic partial response or stable disease) was achieved in 53 patients (50%). Median PFS was 25.0 months (95% CI 16.9-33.1). Patients with radiographic progression <12 months from 4-weekly SSA initiation had worse PFS after dose escalation (7.0 vs. 17.0 months, p = 0.002). In multivariate analysis, pancreatic NETs, a Ki-67 index ≥5% and multiple extrahepatic metastases were independently associated with inferior PFS. CONCLUSIONS: Above-label doses of SSAs may offer a considerable prolongation of PFS and could be utilized as a bridge to other more toxic treatments. Patients with small bowel/colorectal primaries, a Ki-67 index <5% and absence of/limited extrahepatic metastases are more likely to benefit from this approach.

Readmissions among patients with COVID-19.

BACKGROUND: Hospital readmissions are associated with poor patient outcomes and increased health resource utilisation. The need to study readmission patterns is even bigger during a pandemic because the burden is further stretching the healthcare system. METHODS: We reviewed the initial hospitalisation and subsequent readmission for 19 patients with confirmed COVID-19 in the largest statewide hospital network in Rhode Island, US, from March 1st through April 19th, 2020. We also compared the characteristics and clinical outcomes between readmitted and non-readmitted patients. RESULTS: Of the 339 hospitalised patients with COVID-19, 279 discharged alive. Among them, 19/279 were readmitted (6.8%) after a median of 5 days. There was a significantly higher rate of hypertension, diabetes, chronic pulmonary disease, liver disease, cancer and substance abuse among the readmitted compared with non-readmitted patients. The most common reasons of readmissions happening within 12 days from discharge included respiratory distress and thrombotic episodes, while those happening at a later time included psychiatric illness exacerbations and falls. The length of stay during readmission was longer than during index admission and more demanding on healthcare resources. CONCLUSION: Among hospitalised patients with COVID-19, those readmitted had a higher burden of comorbidities than the non-readmitted. Within the first 12 days from discharge, readmission reasons were more likely to be associated with COVID-19, while those happening later were related to other reasons. Readmissions characterisation may help in defining optimal timing for patient discharge and ensuring safe care transition.

Real-Time Spatiotemporal Analysis of Microepidemics of Influenza and COVID-19 Based on Hospital Network Data: Colocalization of Neighborhood-Level Hotspots.

Objectives. To identify spatiotemporal patterns of epidemic spread at the community level.Methods. We extracted influenza cases reported between 2016 and 2019 and COVID-19 cases reported in March and April 2020 from a hospital network in Rhode Island. We performed a spatiotemporal hotspot analysis to simulate a real-time surveillance scenario.Results. We analyzed 6527 laboratory-confirmed influenza cases and identified microepidemics in more than 1100 neighborhoods, and more than half of the neighborhoods that had hotspots in a season became hotspots in the next season. We used data from 731 COVID-19 cases, and we found that a neighborhood was 1.90 times more likely to become a COVID-19 hotspot if it had been an influenza hotspot in 2018 to 2019.Conclusions. The use of readily available hospital data allows the real-time identification of spatiotemporal trends and hotspots of microepidemics.Public Health Implications. As local governments move to reopen the economy and ease physical distancing, the use of historic influenza hotspots could guide early prevention interventions, while the real-time identification of hotspots would enable the implementation of interventions that focus on small-area containment and mitigation.

In-depth analysis of T2Bacteria positive results in patients with concurrent negative blood culture: a case series.

BACKGROUND: T2Bacteria assay uses T2 magnetic resonance (T2MR) technology for the rapid diagnosis of bacterial bloodstream infections (BSIs). This FDA cleared technology can detect 5 of the most prevalent pathogens causing bacteremia (Escherichia coli, Staphylococcus aureus, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Enterococcus faecium). Because the significance of discordant results between the T2Bacteria assay and blood culture (BC) remains a challenge, in this case series we reviewed the medical records of patients who had a positive T2Bacteria test and a concurrent negative BC. METHODS: Among 233 participants, we identified 20 patients with 21 (9%) discordant T2Bacteria-positive/BC-negative (T2+/BC-) results. We classified these results based on clinical cultures and clinical evidence. RESULTS: When we analyzed these 21 discordant results in-depth, 11 (52.5%) fulfilled criteria for probable BSI, 4 (19%) for possible BSI, and 6 (28.5%) were presumptive false positives. Among the probable/possible BSIs, discordant results were often associated with patients diagnosed with closed space and localized infections [pyelonephritis (n = 7), abscess (n = 4), pneumonia (n = 1), infected hematoma (n = 1), and osteomyelitis (n = 1)]. Also, within the preceding 2 days of the T2+/BC- blood sample, 80% (16/20) of the patients had received at least one dose of an antimicrobial agent which was active against the T2Bacteria-detected pathogen. CONCLUSIONS: In the majority of discrepant results, the T2Bacteria assay detected a plausible pathogen that was supported by clinical and/or microbiologic data. Discrepancies appear to be associated with closed space and localized infections and the recent use of effective antibacterial agents. The clinical significance and potential implications of such discordant results should be further investigated.

The association of acute kidney injury with the concomitant use of vancomycin and piperacillin/tazobactam in children: A systematic review and meta-analysis.

Concomitant use of vancomycin plus piperacillin/tazobactam (TZP) has been associated with increased risk of acute kidney injury (AKI) in hospitalized adults. In this systematic review and meta-analysis, we searched PubMed and EMBASE for pediatric studies examining this hypothesis, with reference to vancomycin monotherapy or in combination with another beta-lactam antibiotic. Out of 1381 non-duplicate studies, 10 met our inclusion criteria. We performed a random effects meta-analysis, based on crude odds ratios, and we accounted for both quality of included studies and publication bias. In primary analysis, concomitant vancomycin and TZP use yielded a statistically significant association with the development of AKI. More specifically, children with AKI had higher odds to have been exposed to vancomycin plus TZP, in comparison with vancomycin monotherapy (OR 8.15; 95% CI: 3.49-18.99), or vancomycin plus any other beta-lactam antibiotic (OR 3.48; 95% CI: 2.71-4.46). Based on the results of the Newcastle Ottawa Scale quality assessment, a secondary analysis including only higher quality studies (6 out of 10 studies) yielded again higher odds of exposure to vancomycin plus TZP, compared to vancomycin plus another beta-lactam antibiotic (OR 3.76; 95% CI: 2.56-5.51). Notably, even after controlling for possible publication bias our results remained statistically significant (OR 3.09; 95% CI: 2.30-4.14). In conclusion, the concomitant use of vancomycin and TZP could be associated with AKI development and the clinical significance of this potential association needs to be studied further in the pediatric population.

Metabolic dysfunction-associated steatotic liver disease and its link to cancer.

Metabolic-dysfunction associated steatotic liver disease (MASLD), formerly known as nonalcoholic fatty liver disease (NAFLD), is a growing global health concern with significant implications for oncogenesis. This review synthesizes current evidence on the association between MASLD and cancer risk, highlighting its role as a risk factor for both intrahepatic and extrahepatic malignancies. MASLD is increasingly recognized as a major cause of hepatocellular carcinoma (HCC), with its incidence rising in parallel with the prevalence of metabolic dysfunction. Furthermore, MASLD is associated with an elevated risk of various gastrointestinal cancers, including colorectal, esophageal, stomach, and pancreatic cancers. Beyond the digestive tract, evidence suggests that MASLD may also contribute to an increased risk of other cancers such as breast, prostate, thyroid, gynecological, renal and lung cancers. Understanding the mechanisms underlying these associations and the impact of MASLD on cancer risk is crucial for developing targeted screening and prevention strategies.

Epidemiology of Metabolic Dysfunction-Associated Steatotic Liver Disease

As the rates of obesity and type 2 diabetes (T2D) continue to increase globally, so does the prevalence of metabolic dysfunction associated steatotic liver disease (MASLD). Currently, 38% of all adults and 7-14% of children and adolescents have MASLD. By 2040, the MASLD prevalence rate for adults is projected to increase to over 55%. Although many with MASLD will not develop progressive liver disease, given the vast number of patients with MASLD, it has now become the top indication for liver transplant in the United States for those with hepatocellular carcinoma (HCC) and women. However, the most common cause of mortality among patients with MASLD remains death cardiovascular diseases. In addition to liver outcomes (cirrhosis and HCC), MASLD is associated with increased risk for the developing de-novo T2D, chronic kidney disease, sarcopenia and extrahepatic cancers. Furthermore, MASLD is associated with decreased health related quality of life, decreased work productivity, fatigue and increased healthcare resource utilization and substantial economic burden. Similar to other metabolic disease, lifestyle interventions with heathy diet and increased physical activity remain the cornerstone of managing these patients. Although a number of obesity and T2D drugs are available to treat co-morbid disease, Resmetirom is the only MASH-targeted medication that was recently approved by the Federal Drug Administration for use in the United States for those with stage 2-3 fibrosis. The following review provides an overview of MASLD epidemiology, its related risk factors and outcomes and demonstrates that without further global initiatives, MASLD may continue to increase.

Risk of infection in patients with hidradenitis suppurativa on biologics or other immunomodulators: a systematic review and meta-analysis.

Hidradenitis suppurativa (HS) is a painful skin condition that significantly affects patients' quality of life. Biologic agents, including anti-TNF agents and IL-17 inhibitors, have shown promise as treatment options for HS. However, there is concern about the increased risk of infections associated with these therapies. We conducted a systematic review and meta-analysis following PRISMA and MOOSE guidelines. We searched PubMed and Embase until February 1, 2023. The primary outcome of interest was the incidence of any infectious complications. Secondary outcomes included serious and opportunistic infections in HS patients treated with biologics or other immunomodulators. Twenty-four studies met our inclusion criteria, comprising 1,696 patients. The pooled incidence rate for any infection was 24.2%, primarily consisting of mild respiratory and skin infections. Subgroup analysis based on the mechanism of action (MOA) showed a pooled incidence of 7.77% for anti-IL1, 14.24% for anti-PDE4, and 21.96% for anti-TNF. Notably, patients receiving anti-IL17 had the highest incidence rate of infection at 33.6%, but the relative risk compared to placebo was not significantly elevated (0.99, 95% CI: 0.86-1.14). Serious infections were rare, with pooled incidences of 0.39% for anti-IL17 and 0.03% for anti-TNF. Opportunistic infections were infrequent, with 10 reported cases, including eight oral candidiasis, one cryptosporidiosis, and one Blastocystis hominis infection. The use of biologic therapies in HS patients does not significantly increase the risk of infectious complications. Additionally, the occurrence of serious or opportunistic infections in HS patients treated with biologics appears to be minimal.

Machine learning-assisted high-throughput screening for Anti-MRSA compounds.

BACKGROUND: Antimicrobial resistance is a major public health threat, and new agents are needed. Computational approaches have been proposed to reduce the cost and time needed for compound screening. AIMS: A machine learning (ML) model was developed for the in silico screening of low molecular weight molecules. METHODS: We used the results of a high-throughput Caenorhabditis elegans methicillin-resistant Staphylococcus aureus (MRSA) liquid infection assay to develop ML models for compound prioritization and quality control. RESULTS: The compound prioritization model achieved an AUC of 0.795 with a sensitivity of 81% and a specificity of 70%. When applied to a validation set of 22,768 compounds, the model identified 81% of the active compounds identified by high-throughput screening (HTS) among only 30.6% of the total 22,768 compounds, resulting in a 2.67-fold increase in hit rate. When we retrained the model on all the compounds of the HTS dataset, it further identified 45 discordant molecules classified as non-hits by the HTS, with 42/45 (93%) having known antimicrobial activity. CONCLUSION: Our ML approach can be used to increase HTS efficiency by reducing the number of compounds that need to be physically screened and identifying potential missed hits, making HTS more accessible and reducing barriers to entry.

Risk of Infection in Patients With Inflammatory Bowel Disease Treated With Interleukin-Targeting Agents: A Systematic Review and Meta-Analysis.

BACKGROUND: Patients with inflammatory bowel disease (IBD) are at increased risk of infection. The aim of this study was to assess the cumulative incidence and risk of infection in patients with IBD treated with interleukin (IL)-targeting agents. METHODS: We searched PubMed, EMBASE, and Web of Science for randomized controlled trials including patients with IBD receiving IL-targeting agents compared with patients receiving placebo or treatment that only differed from the intervention arm in the absence of an IL-targeting agent. The primary outcome of interest was the relative risk (RR) of any-grade and severe infection during the induction phase. RESULTS: There was no difference in risk of any-grade (RR, 0.98; 95% confidence interval [CI], 0.89-1.09) or severe (RR, 0.64; 95% CI, 0.38-1.10) infection in patients receiving any IL-targeting agent compared with the control group. During the maintenance period, the cumulative incidence of any-grade infection in patients receiving IL-12/23p40-targeting agents (mean follow-up 29 weeks) was 34.82% (95% CI, 26.78%-43.32%), while the cumulative incidence of severe infection was 3.07% (95% CI, 0.93%-6.21%). The cumulative incidence of any-grade infection in patients receiving IL-23p19-targeting agents (mean follow-up 40.9 weeks) was 32.16% (95% CI, 20.63%-44.88%), while the cumulative incidence of severe infection was 1.75% (95% CI, 0.60%-3.36%). During the maintenance phase of the included studies, the incidence of infection was 30.66% (95% CI, 22.12%-39.90%) for any-grade and 1.59% (95% CI, 0.76%-2.63%) for severe infection in patients in the control group. CONCLUSIONS: There was no difference in risk of infection between patients with IBD who received IL-targeting agents compared with the control group. Case registries and randomized controlled trials reporting the safety of IL inhibitors should provide detailed information about the risk of specific infectious complications in patients with IBD receiving IL-targeting agents.

Patients with inflammatory bowel disease treated with interleukin-targeting agents are not more likely to develop any-grade or severe infection compared with patients with inflammatory bowel disease receiving placebo or treatment that only differs in the absence of an interleukin-targeting agent.

Changes in the epidemiological trends of primary liver cancer in the Asia-Pacific region.

Primary liver cancer is the third leading cause of cancer-related mortality. The increasing prevalence of metabolic syndrome and alcohol consumption, along with the existing burden of viral hepatitis, could significantly heighten the impact of primary liver cancer. However, the specific effects of these factors in the Asia-Pacific region, which comprises more than half of the global population, remain largely unexplored. This study aims to analyze the epidemiology of primary liver cancer in the Asia-Pacific region. We evaluated regional and national data from the Global Burden of Disease study spanning 2010 to 2019 to assess the age-standardized incidence, mortality, and disability-adjusted life years associated with primary liver cancer in the Asia-Pacific region. During the study period, there were an estimated 364,700 new cases of primary liver cancer and 324,100 deaths, accounting for 68 and 67% of the global totals, respectively. Upward trends were observed in the age-standardized incidence rates of primary liver cancer due to metabolic dysfunction-associated fatty liver disease (MASLD) and alcohol-associated liver disease (ALD) in the Asia-Pacific region, as well as an increase in primary liver cancer from Hepatitis B virus infection in the Western Pacific region. Notably, approximately 17% of new cases occurred in individuals aged 15-49 years. Despite an overall decline in the burden of primary liver cancer in the Asia-Pacific region over the past decade, increases in incidence were noted for several etiologies, including MASLD and ALD. However, viral hepatitis remains the leading cause, responsible for over 60% of the total burden. These findings underscore the urgent need for comprehensive strategies to address the rising burden of primary liver cancer in the Asia-Pacific region.

Incidence and potential risk factors for remdesivir-associated bradycardia in hospitalized patients with COVID-19: A retrospective cohort study.

Background: Remdesivir is widely used for the management of COVID-19 and several studies have reported bradycardia as a potential side effect associated with this agent. The aim of the present study was to evaluate the incidence rate, severity, and potential risk factors of remdesivir-associated bradycardia. Methods: We performed a retrospective cohort study among hospitalized adult patients with COVID-19 who were treated with remdesivir from March 2020 to October 2021. Our primary outcome of interest was the incidence rate and severity of bradycardia after remdesivir administration. We defined mild bradycardia as a heart rate of 51-59 beats per minute, moderate bradycardia as a heart rate of 41-50 beats per minute, and severe bradycardia as a heart rate of ≤40 beats per minute. We also performed univariable and multivariable regression analyses to determine potential bradycardia risk factors. Baseline characteristics were reported as means with standard deviations or medians with interquartile ranges (IQRs). All the statistical tests are shown as odds ratios (ORs) with 95% confidence intervals (CIs). Results: In total, 1,635 patients were included in this study. The median age with IQR was 68 (57-79) years and 51.7% of the patients were male. In total, 606 (37.1%) patients developed bradycardia. Among them, 437 patients (26.7%) developed mild bradycardia, 158 patients (9.7%) moderate bradycardia, while 11 patients (0.7%) experienced severe bradycardia. In our adjusted multivariate logistic regression, the odds of bradycardia development after remdesivir administration were higher among patients with age ≥65 years (OR 1.76, 95% CI: 1.04-2.99, p = 0.04), those with hypertension (OR 1.37, 95% CI: 1.07-1.75, p = 0.01), and obesity (OR 1.32, 95% CI: 1.02-1.68, p = 0.03). Conclusion: More than 1 out of 3 patients (37%) who received remdesivir for COVID-19 developed bradycardia with the majority of these patients developing mild or moderate bradycardia that is usually a benign manifestation not needing treatment in most cases. Age ≥65 years, hypertension, and obesity were potential risk factors for remdesivir-associated bradycardia among hospitalized COVID-19 patients. Clinicians should be aware of this adverse event and consider close clinical monitoring for patients at high risk for this adverse event.

Combination Systemic Therapies in Advanced Well-Differentiated Gastroenteropancreatic Neuroendocrine Tumors (GEP-NETs): A Comprehensive Review of Clinical Trials and Prospective Studies.

There is an evolving landscape of systemic combination regimens for patients with advanced well-differentiated gastroenteropancreatic neuroendocrine tumors (GEP-NETs). In this review, we provide a comprehensive outline of the existing clinical trials/prospective studies investigating these combinations. PubMed was searched using key relevant terms to identify articles referring to GEP-NETs and combination treatments. No systematic search of the literature or metanalysis of the data was performed, and we focused on the most recent literature results. Primarily, phase 1 and 2 clinical trials were available, with a smaller number of phase 3 trials, reporting results from combination treatments across a wide range of antiproliferative agents. We identified significant variability in the anti-tumor activity of the reported combinations, with occasional promising results, but only a very small number of practice-changing phase 3 clinical trials. Overall, the peptide receptor radionuclide therapy (PRRT)-based combinations (with chemotherapy, dual PPRT, and targeted agents) and anti-vascular endothelial growth factor (VEGF) agent combinations with standard chemotherapy were found to have favorable results and may be worth investigating in future, larger-scale trials. In contrast, the immune-checkpoint inhibitor-based combinations were found to have limited applicability in advanced, well-differentiated GEP-NETs.