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The global prevalence and impact of steatotic liver disease and viral infections: A systematic review and meta-analysis
Get PDFBackground: Steatotic liver disease (SLD) affects ~30% of adults worldwide. The global population is continuously threatened by epidemic and endemic viral diseases. This study aims to thoroughly examine the interaction between SLD and major viral diseases.
Methods: We systematically searched databases from inception to April 2, 2024, for observational studies recording viral-infected adult patients with eligible data on the presence of hepatic steatosis.
Results: Six hundred thirty-six eligible studies were included in the analysis of SLD prevalence. Among patients with monoinfections, the highest SLD prevalence was observed in those infected with HCV at 49% (95% CI: 47%-51%), followed by SARS-CoV-2 (39%, 95% CI [34%-44%]), HIV (39%, 95% CI [33%-44%]), and HBV (36%, 95% CI [32%-40%]). Additionally, co-infections, such as HCV-HIV and HBV-HCV, exhibit even higher SLD prevalence. The prevalence of steatohepatitis is particularly high in HIV-infected (24%, 95% CI: 17%-30%) and HCV-infected (18%, 95% CI: 13%-24%) populations. The co-existence of SLD with viral infections was associated not only with the progression of liver disease but also with more severe outcomes of the infections and poorer responses to antiviral treatment. The combination of cardiometabolic risk factors and viral-associated and host factors contributes to the higher risk of SLD in viral-infected populations.
Conclusions: SLD is highly prevalent in viral-infected populations, and the reciprocal interactions between SLD and viral diseases exacerbate both conditions, leading to poorer patient outcomes in general
Efficient transduction of pancreas tissue slices with genetically encoded calcium integrators
No full textThis study combines live pancreas tissue slices with adenoviral transduction of the Calcium Modulated Photoactivatable Ratiometric Integrator 2 (CaMPARI2) biosensor for high-throughput analysis of islet calcium responses. Pancreas slices preserve islets within their native microenvironment, adding tissue context to the study of islet function and pathology. A key challenge of the pancreas slice model has been efficient transgene delivery while maintaining viability and function. Here, we demonstrate a robust adenoviral gene delivery approach using targeted and universal promoters. By transducing slices with CaMPARI2 and applying 405 nm photoconverting light, we permanently marked glucose-induced calcium activity across entire islet populations while preserving the in situ tissue context. Applied to nPOD donor tissues, including from individuals with type 1 diabetes, type 2 diabetes, and non-diabetic controls, this approach demonstrated glucose responsive CaMPARI2 labeling that correlated with insulin secretion. Integrating CaMPARI2 with pancreas slices enables multiplexed analyses, linking a functional readout with spatial context through immunostaining or gene expression to advance understanding of human islet behavior
Randomized Phase II Study of Nab-Paclitaxel and Gemcitabine With or Without Tocilizumab as First-Line Treatment in Advanced Pancreatic Cancer: Survival and Cachexia
No full textPurpose: This randomized phase-II trial (ClinicalTrials.gov identifier: NCT02767557) compared efficacy of gemcitabine/nab-paclitaxel (Gem/Nab) with or without the anti-interleukin-6 (IL-6) receptor antibody tocilizumab (Toc) for advanced pancreatic cancer (PC).
Methods: A safety cohort received Gem 1,000 mg/m2 and Nab 125 mg/m2 on days 1, 8, and 15, and Toc 8 mg/kg on day 1 for each 28-day cycle. Participants with modified Glasgow prognostic scores of 1 or 2 were randomly assigned 1:1 to receive Gem/Nab/Toc or Gem/Nab. The primary end point was the overall survival (OS) rate at 6 months (OS6). Secondary end points were progression-free survival (PFS), overall response rate (ORR), and safety. Exploratory end points were cachexia, quality of life, and biomarkers, including the cachexia-promoting protein, growth differentiation factor 15 (GDF15).
Results: Overall, 147 patients were treated, including six safety cohort participants. The median follow-up period was 8.1 months (IQR, 4.2-13.9). OS6 was 68.6% (95% CI, 56.3 to 78.1) for the Gem/Nab/Toc group and 62.0% (49.6-72.1) for the Gem/Nab group (P = .409). OS for Gem/Nab/Toc versus Gem/Nab improved at 18 months (27.1% v 7.0%, P = .001). No differences in median OS, PFS, or ORR were observed. Incidence of grade-3+ treatment-related adverse events (TrAEs) was 88.1% for Gem/Nab/Toc and 63.4% for Gem/Nab (P < .001). Gem/Nab/Toc decreased muscle loss versus Gem/Nab, with median change +0.1013% versus -3.430% (P = .0012) at 2 months and +0.7044 versus -3.353% (P = .036) at 4 months. Incidence of muscle loss was 43.48% on Gem/Nab/Toc versus 73.52% on Gem/Nab at 2 months (P = .0045) and 41.82% versus 68.75% (P = .0062) at 4 months. GDF15 was not changed by Gem/Nab or Gem/Nab/Toc.
Conclusion: Although the primary end point was not met and TrAEs were increased by Toc, increased survival at 18 months and reduced muscle wasting support an anticachexia effect of IL-6 blockade independent of GDF15. Further studies could leverage these findings for precision anticachexia therapy
An Erroneous Argument for Error Theory
No full textIn Cowie’s “Why Moral Paradoxes Support Error Theory,” he argues that recent work in moral theory shows that error theory fares no worse than other metaethical theories when it comes to ordinary moral judgment, and he argues that this suffices to answer the fundamental challenge for error theory. This article shows that Cowie’s argument does not work. More specifically, it is shown that the counterintuitive implications of error theory dominate those of realism, in both a technical, quantitative sense, and in a non-technical, qualitative sense. If Cowie is correct that, in the absence of an answer to the fundamental challenge, error theory should be rejected out of hand, then this constitutes a serious setback to the error theorist’s program
Impact of mirikizumab treatment on fatigue in patients with moderately to severely active Crohn's disease: results from the phase 3 VIVID-1 study
No full textBackground: Fatigue is a debilitating multifactorial symptom experienced by patients with Crohn's disease (CD). Mirikizumab, an anti-interleukin-23p19 antibody, demonstrated significant efficacy and safety in the patients with moderately to severely active CD. This analysis investigated the impact of mirikizumab on fatigue and the association between changes in clinical, endoscopic, and patient-reported outcomes with improvement in fatigue from baseline in the Phase 3 VIVID-1 study.
Methods: Adult patients with moderately to severely active CD that failed at least 1 biologic agent or conventional therapy were randomized to receive mirikizumab or placebo. Fatigue was assessed via the validated Functional Assessment of Chronic Illness Therapy-Fatigue questionnaire. Fatigue associations with patient-reported outcomes, endoscopic, and clinical measures were assessed via Pearson correlation analysis.
Results: At Week 12, 43% and 33%, and at Week 52, 46% and 36% of mirikizumab-treated patients achieved ≥ 6 and ≥ 9 fatigue score improvements vs placebo (Week 12, 31%, 22%; Week 52, 20%, 16%), respectively. Baseline fatigue scores were strongly associated with depressive symptoms and moderately associated with quality of life (QoL) at baseline. Improvements in fatigue at Weeks 12 and 52 were strongly associated with QoL and patient-reported outcomes and weakly with objective markers of inflammation and disease activity.
Conclusions: Mirikizumab-treated patients with CD achieved higher rates of clinically meaningful improvement in fatigue vs placebo at Weeks 12 and 52, which correlated with improvement in clinical and patient-reported outcomes. Baseline fatigue severity was strongly associated with depressive symptoms in VIVID-1 (NCT03926130)
Vitamin D Deficiency and Driveline Infections in Patients With Left Ventricular Assist Devices
No full textBackground: Despite major advancements in the field of durable left ventricular assist devices (LVADs), driveline infection is a major source of morbidity and mortality. Risk factors have been proposed, but few are modifiable. We evaluated vitamin D deficiency as a potential modifiable risk factor for driveline infection.
Methods and results: This single-center, retrospective study included 134 LVAD recipients between 2010 and 2022. Patients were divided into two groups based on their pre-implant vitamin D levels: the vitamin D sufficient group (≥ 30 ng/mL) and the vitamin D deficient group (< 30 ng/mL). The Kaplan-Meier method estimated 18-month freedom from driveline infection. The Cox proportional hazards model estimated the effect of vitamin D deficiency on driveline infections. Kaplan-Meier estimates for infection-free survival were significantly higher in the sufficient group (90.5% vs. 69.6%, p = 0.014). Vitamin D deficiency (HR: 3.644, 95% CI: 1.271-10.448, p = 0.016) and obesity (HR: 3.190, 95% CI: 1.464-7.400, p = 0.004) were found to be independent risk factors for driveline infection.
Conclusion: Our findings support vitamin D deficiency as a potential modifiable risk factor for driveline infection. Obesity was also noted as a significant risk factor for infection. Further research is warranted to establish causality and assess the impact of vitamin D repletion on infection rates
The complexities of pain in heart failure: locations, comorbid conditions, medications, subtypes, and limitations with activities
No full textPreventing Meningococcal Disease in US Adolescents and Young Adults Through Vaccination
No full textIn 2022, experts convened under the name Advancing Strategies to Prevent Meningococcal Disease (ARTEMIS) to gather insights on issues related to invasive meningococcal disease (IMD) and meningococcal vaccination in the US. Discussions regarding successes, challenges, and future directions for the US meningococcal vaccination program are summarized. Current vaccination recommendations target adolescents/young adults (AYA), who are at increased risk of IMD. Suboptimal vaccination rates, particularly for meningococcal serogroup B disease, may stem from gaps in knowledge surrounding IMD and meningococcal vaccination among healthcare providers (HCPs), parents, and AYA; confusion among HCPs regarding the shared clinical decision-making recommendation for serogroup B vaccinations; demographic variables; and lack of preventive healthcare visits. ARTEMIS proposed strategies to address knowledge gaps and access barriers at the HCP, parent/AYA, and educational institution/policymaker levels. Alternative vaccination schedules using a recently approved MenABCWY vaccine that provides protection against all five major serogroups may simplify meningococcal vaccination and increase coverage
Attention-Deficit/Hyperactivity Disorder as a Mediating Variable for Invalid Baseline Profiles on the ImPACT
No full textBackground: Individuals with ADHD may perform poorly on tasks targeting executive functioning skills such as the ImPACT, which requires the test-taker to employ judgement in non-routine situations Objective: To determine whether ADHD serves as a mediating variable for increasing the likelihood of an invalid score.
Materials and methods: A total of 39,140 collegiate athletes and United States military cadets consented to the Concussion Assessment, Research, and Education (CARE) Consortium study. Participants completed the CARE Baseline Packet which included various sections through which study participants provide self-report data, including demographic, personal, and family history sections. The personal history portion of the CARE Baseline Packet addressed the participant's neurological history, including self-reported diagnosis of ADHD and history of traumatic brain injury. Variables utilized for the current study included age, gender, race, ethnicity, the participant's primary college sport, use of mouthguards for athletes competing in sports requiring them, and the presence of an ADHD diagnosis. Participants responded to a question, inquiring if they had ever been diagnosed by a medical professional with ADHD, ultimately producing a dichotomous yes/no response.
Results: We found that participants with ADHD were more likely to produce invalid baseline scores (ß = -0.884; p < 0.001). Similar results were found when controlling for sex, race, age, sport played, mouthguard use, and number of previous concussions (ß = -0.786; p < 0.001). Sex, race, sport played, and mouthguard use each played a significant role in determining profile validity, independent of ADHD diagnosis. With ADHD removed from the model, age negatively affected the likelihood of a valid score (ß = -0.052; p = 0.048).
Conclusions: Our study suggests that the relationship between age and ImPACT validity is explained by the presence of ADHD. Results support adjusting ImPACT's validity thresholds for individuals with ADHD