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The article presents a study on the use of recombinant activated factor VII (rFVIIa) for refractory hemorrhage in pediatric patients on extracorporeal membrane oxygenation (ECMO). The study aims to add safety and efficacy data to existing literature. The result of the study suggests the limited efficacy for rFVIIa use for refractory hemorrhage in pediatric patients on ECMO support.

Background and Aims: The prevalence of Metabolic Dysfunction-Associated Steatotic Liver Disease has increased in parallel with a rise in consumption of ultra-processed foods (UPF), but little is known about their association., Methods: We cross-sectionally examined associations of UPF with hepatic steatosis and fibrosis in 2458 (mean age 54 years; 55.9 % women) community-dwelling adults who completed vibration-controlled transient elastography and a food frequency questionnaire. Dietary intake was categorized into levels of food processing via the NOVA system. We used multivariable-adjusted logistic regression models to evaluate the association of energy-adjusted UPF intake (per 1-SD unit and by quintile) with clinical hepatic steatosis (Controlled Attenuation Parameter [CAP]≥ 290 dB/m) and fibrosis (Liver Stiffness Measurement [LSM] ≥ 8.2 kPa) and tested for linear trends of UPF intake with CAP and LSM. We adjusted for age, sex, smoking, alcohol intake, physical activity, and intake of minimally processed foods. Additional models adjusted for diet quality index or body mass index (BMI)., Results: Higher intake of UPF was directly associated with higher odds of hepatic steatosis (Odds Ratio 1.33 [95 % Confidence Interval 1.21, 1.46] per standard deviation increase). UPF intake and CAP had a dose-response relation (P trend <0.001). There were 2.50 times higher odds of hepatic steatosis (Confidence Interval 1.81, 3.45) with a 19.49 (standard error: 3.73) unit increase in CAP (P < 0.001) when comparing quintile 5 to quintile 1 of UPF consumption. Higher UPF was not significantly associated with hepatic fibrosis. Adjustment for BMI attenuated the strength of all UPF-hepatic associations., Conclusions: UPF consumption was positively associated with hepatic steatosis. Longitudinal studies are needed to assess whether lowering consumption of UPF can decrease odds of hepatic fibrosis., Competing Interests: Declaration of competing interest Michelle T. Long is employed full time by Novo Nordisk A/S. All other authors have no relevant conflicts of interest., (Copyright © 2025 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.)

Objectives: Diabetes mellitus has been associated with greater difficulty of tracheal intubation in the operating room. This relationship has not been examined for tracheal intubation of critically ill adults. We examined whether diabetes mellitus was independently associated with the time from induction of anesthesia to intubation of the trachea among critically ill adults., Design: A secondary analysis of data from five randomized trials completed by the Pragmatic Critical Care Research Group (PCCRG)., Setting: Emergency departments (EDs) or ICUs at 11 centers across the United States that enrolled in randomized trials of a pre-intubation checklist, fluid bolus administration, bag-mask ventilation between induction and laryngoscopy, and intubation using a bougie vs. stylet., Patients: Critically ill adults undergoing tracheal intubation with a laryngoscope in an ED or an ICU., Interventions: None., Measurements and Main Results: A total of 2654 patients were included in this analysis, of whom 638 (24.0%) had diabetes mellitus. The mean time from induction of anesthesia to intubation of the trachea was 169 seconds (sd, 137s). Complications occurred during intubation in 1007 patients (37.9%). Diabetes mellitus was not associated with the time from induction of anesthesia to intubation of the trachea (-4.4 s compared with nondiabetes; 95% CI, -17.2 to 8.3 s; p = 0.50). Use of a video vs. direct laryngoscope did not modify the association between diabetes mellitus and the time from induction to intubation (p for interaction = 0.064). Diabetes mellitus was not associated with the probability of successful intubation on the first attempt (85.6% vs. 84.3%; p = 0.46) or complications during intubation (39.8% vs. 37.4%; p = 0.52)., Conclusions: Among 2654 critically ill patients undergoing tracheal intubation in an ED or an ICU, diabetes mellitus was not independently associated with the time from induction to intubation, the probability of successful intubation on the first attempt, or the rate of complications during intubation., Competing Interests: Dr. Krause was supported in part by grants from the National Institutes of Health (NIH)/National Institute on Deafness and Other Communication Disorders and NIH/National Institute of Neurological Disorders and Stroke. Dr. de Jong reports receiving remuneration for presentations from Medtronic, Sedana, Drager, Viatris, Sanofi, and Fisher & Paykel. Dr. Casey was supported in part by grants from the NIH/National Center for Advancing Translational Sciences (NCATS), the NIH/National Heart, Lung, and Blood Institute (NHLBI), the Department of Defense, and the Patient-Centered Outcomes Research Institute. Dr. Casey reported having received a travel grant from Fischer and Paykel. Dr. Ginde was supported by grants from the Department of Defense related to the current work, and grants from NIH and Centers for Disease Control and Prevention and consulting fees from Seastar and Biomeme, unrelated to the current work. Dr. Hughes was supported in part by the NIH (AG061161, AG080420, AG053582, GM120484, HL151951, and HL164909). Dr. Hughes has received consulting fees from Sedana Medical as members of their U.S. Trials Steering Committee. Dr. Khan has received grant support from Dompe Pharmaceuticals, 4D Medical, Eli Lilly, United Therapeutics, and NIH/NHLBI. Dr. Mitchell received travel-related funding support for a research trial from Sharpmed. Dr. Semler was support in part by grants from the NIH/NCATS, the NIH/NHLBI, the Department of Defense, and the Patient-Centered Outcomes Research Institute. Dr. Semler reported having received compensation from Baxter Healthcare Corporation for having delivered a virtual lecture at a conference and for having served on a medical advisory board. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2024 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)

Background and Aims: Individuals with steatotic liver disease (SLD) are at high cardiovascular disease (CVD) risk, but approaches to characterise and mitigate this risk are limited. By investigating relations, and shared metabolic pathways, of hepatic steatosis/fibrosis and cardiorespiratory fitness (CRF), we sought to identify new avenues for CVD risk reduction in SLD., Methods: In Framingham Heart Study (FHS) participants (N = 2722, age 54 ± 9 years, 53% women), vibration-controlled transient elastography (VCTE) was performed between 2016-2019 to assess hepatic steatosis (continuous attenuation parameter [CAP]) and fibrosis (liver fibrosis measure [LSM]). Concurrently, participants underwent maximum effort cardiopulmonary exercise testing (CPET), and metabolomic profiling (201 circulating metabolites) was performed in a subsample (N = 1268)., Results: Mean BMI was 28.0 ± 5.3, 27% had hepatic steatosis, 7.6% had fibrosis, and peak oxygen uptake (VO 2 ) was 26.2 ± 6.8 mL/kg/min in men and 20.7 ± 6.0 mL/kg/min in women (95% predicted overall). In linear models adjusted for cardiometabolic risk factors, greater CAP and LSM were associated with lower peak VO 2 (p ≤ 0.002 for all), and the CAP association remained significant after BMI adjustment (p < 0.0001). We observed shared metabolic architecture of CAP, LSM, and peak VO 2 , with metabolites mediating up to 35% (for CAP) and 74% (for LSM) of the association with peak VO 2 . Metabolite mediators included amino acids and derivatives implicated in cardiometabolic risk and both protective and deleterious lipid species., Conclusions: Hepatic steatosis and fibrosis are associated with CRF impairment in the community, and these relations are partly mediated by pathways of altered lipid metabolism and general cardiometabolic risk., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been detected in multiple animal species, including white-tailed deer (WTD), raising concerns about zoonotic transmission, particularly in environments with frequent human interactions. To understand how human exposure influences SARS-CoV-2 infection in WTD, we compared infection and exposure prevalence between farmed and free-ranging deer populations in Florida. We also examined the timing and viral variants in WTD relative to those in Florida's human population. Between 2020 and 2022, we collected respiratory swabs (N = 366), lung tissue (N = 245), retropharyngeal lymph nodes (N = 491), and serum specimens (N = 381) from 410 farmed and 524 free-ranging WTD. Specimens were analyzed using RT-qPCR for infection and serological assays for exposure. SARS-CoV-2 infection was detected in less than 1% of both northern Florida farmed (0.85%) and free-ranging (0.76%) WTD. No farmed deer possessed virus-neutralizing antibodies, while one free-ranging WTD tested positive for SARS-CoV-2 antibodies (3.45%). Viral sequences in infected WTD matched peaks in human cases and circulating variants, indicating human-to-deer spillover but at a lower frequency than reported elsewhere. Our findings suggest a reduced risk of SARS-CoV-2 spillover to WTD in northern Florida compared to other regions, highlighting the need for further research on transmission dynamics across North America.

This 42-d study evaluated the effects of phytase, calcium butyrate (CB), and bacitracin methylene disalicylate 50 (BMD) on broiler performance, processing yields, and nutrient digestibility. Ross YPM x 708 male broilers (2,880 total) were distributed in 72 floor pens and assigned to 1 of 9 treatments (8 replicates/treatment) on d of hatch. This experiment was a 2 × 4 + 1 factorial arrangement, including 2 phytase concentrations (500 or 1,500 FTU/kg), 4 microbiota modulating feed additive groups (MMFA; none, CB (0.5 g/kg of diet), BMD (55 mg/kg of diet), or both CB and BMD), and a negative control without feed additives. Broiler performance (d 14, 28, and 42), apparent ileal nutrient digestibility (d 28 and 42), and processing yields (d 43) were determined. Day 14 BW increased with BMD inclusion compared to CB and no MMFA in the 1,500 FTU/kg group but BW were similar between all MMFA combined with 500 FTU/kg (P ≤ 0.05). Supplementing BMD increased d 28 BW and reduced d 1 to 28 feed conversion ratio compared to CB and no MMFA (main effect, P ≤ 0.05). Day 42 BW varied depending on dietary phytase concentrations. When diets contained 500 FTU/kg, broilers fed both CB and BMD had a higher BW than broilers fed only CB. Whereas when the inclusion of phytase was increased to 1,500 FTU/kg, broilers fed diets with only BMD or both CB and BMD had higher BW than broilers fed diets with no MMFA (P ≤ 0.05). Phytase concentrations at 1,500 FTU/kg increased (P ≤ 0.05) digestibility of fat (main effect, d 42), phosphorus (d 28 and 42), and apparent ileal digestible energy (main effect, d 42) compared to 500 FTU/kg. In this study, dietary BMD improved broiler growth compared to CB and no MMFA. However, these observed differences between CB and BMD were dependent on dietary phytase concentrations., Competing Interests: DISCLOSURES The authors declare no conflicts of interest., (Published by Elsevier Inc.)

Recent updates in nomenclature and diagnostic criteria encompass the diverse phenotypes associated with steatotic liver disease (SLD). 1 These updates aim to reflect the current understanding of SLD, promote disease awareness and research, and reduce stigma. Notably, the term metabolic dysfunction-associated steatotic liver disease (MASLD) is defined as hepatic steatosis with at least 1 of 5 cardiometabolic criteria without any other cause of steatosis. A new category, MetALD, includes those with MASLD and high alcohol intake. 1 We aimed to characterize SLD using this nomenclature in the Framingham Heart Study (FHS) and to quantify its association with cardiometabolic risk factors., (Copyright © 2024 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background: Eggs are rich in bioactive compounds, including choline and carotenoids that may benefit cardiometabolic outcomes. However, little is known about their relationship with nonalcoholic fatty liver disease (NAFLD)., Objectives: We investigated the association between intakes of eggs and selected egg-rich nutrients (choline, lutein, and zeaxanthin) and NAFLD risk and changes in liver fat over ∼6 y of follow-up in the Framingham Offspring and Third Generation cohorts., Methods: On 2 separate occasions (2002-2005 and 2008-2011), liver fat was assessed using a computed tomography scan to estimate the average liver fat attenuation relative to a control phantom to create the liver phantom ratio (LPR). In 2008-2011, cases of incident NAFLD were identified as an LPR ≤0.33 in the absence of heavy alcohol use, after excluding prevalent NAFLD (LPR ≤0.33) in 2002-2005. Food frequency questionnaires were used to estimate egg intakes (classified as <1, 1, and ≥2 per week), dietary choline (adjusted for body weight using the residual method), and the combined intakes of lutein and zeaxanthin. Multivariable modified Poisson regression and general linear models were used to compute incident risk ratios (RR) of NAFLD and adjusted mean annualized liver fat change., Results: NAFLD cumulative incidence was 19% among a total of 1414 participants. We observed no associations between egg intake or the combined intakes of lutein and zeaxanthin with an incident NAFLD risk or liver fat change. Other diet and cardiometabolic risk factors did not modify the association between egg intake and NAFLD risk. However, dietary choline intakes were inversely associated with NAFLD risk (RR for tertile 3 compared with tertile 1: 0.69, 95% CI: 0.51, 0.94)., Conclusions: Although egg intake was not directly associated with NAFLD risk, eggs are a major source of dietary choline, which was strongly inversely associated with NAFLD risk in this community-based cohort., Competing Interests: Conflict of interest statement The authors report no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Importance: In-hospital cardiac arrest (IHCA) is a significant public health burden. Rates of return of spontaneous circulation (ROSC) have been improving, but the best way to care for patients after the initial resuscitation remains poorly understood, and improvements in survival to discharge are stagnant. Existing North American cardiac arrest databases lack comprehensive data on the post-resuscitation period, and we do not know current post-IHCA practice patterns. To address this gap, we developed the Discover In-Hospital Cardiac Arrest (Discover IHCA) study, which will thoroughly evaluate current post-IHCA care practices across a diverse cohort., Objectives: Our study collects granular data on post-IHCA treatment practices, focusing on temperature control and prognostication, with the objective of describing variation in current post-IHCA practice., Design, Setting, and Participants: This is a multicenter, prospectively collected, observational cohort study of patients who have suffered IHCA and have been successfully resuscitated (achieved ROSC). There are 24 enrolling hospital systems (23 in the United States) with 69 individual enrolling hospitals (39 in the United States). We developed a standardized data dictionary, and data collection began in October 2023, with a projected 1000 total enrollments. Discover IHCA is endorsed by the Society of Critical Care Medicine., Interventions, Outcomes, and Analysis: The study collects data on patient characteristics including pre-arrest frailty, arrest characteristics, and detailed information on post-arrest practices and outcomes. Data collection on post-IHCA practice was structured around current American Heart Association and European Resuscitation Council guidelines. Among other data elements, the study captures post-arrest temperature control interventions and post-arrest prognostication methods. Analysis will evaluate variations in practice and their association with mortality and neurologic function., Conclusions: We expect this study, Discover IHCA, to identify variability in practice and outcomes following IHCA, and be a vital resource for future investigations into best-practice for managing patients after IHCA., Competing Interests: The authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2024 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine.)

Purpose of Review: Vitamin C can be a potential adjunctive treatment option for critically ill individuals due to its pleiotropic effects as electron donor in many enzymatic reactions throughout the body. Recently, several important randomized controlled trials (RCTs) investigating vitamin C in critically ill patients have been published., Recent Findings: Two recent large RCTs administering high-dose vitamin C to patients with sepsis and COVID-19 showed signs of harm. Though performed at high standard, these trials had several limitations. Recent studies in cardiac surgery and burns showed decreased cardiac enzymes and improved clinical outcomes after cardiac surgery, and decreased fluid requirements, reduced wound healing time and in-hospital mortality after burns. Vitamin C may hold benefit in the management of other ischemia/reperfusion injury populations, including postcardiac arrest patients and after solid organ transplantation. Currently, covering basal vitamin C requirements during critical illness is recommended, though the exact dose remains to be determined., Summary: Future work should address optimal vitamin C timing, since early versus late drug administration are likely distinct, and duration of therapy, where withdrawal-induced injury is possible. Additionally accurate assessment of body stores with determination of individual vitamin requirements is crucial to ascertain patient and subgroups most likely to benefit from vitamin C., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Arterial stiffening may contribute to the pathogenesis of metabolic dysfunction-associated steatotic liver disease. We aimed to assess relations of vascular hemodynamic measures with measures of hepatic steatosis and fibrosis in the community., Methods: Our sample was drawn from the Framingham Offspring, New Offspring Spouse, Third Generation, Omni-1, and Omni-2 cohorts (N=3875; mean age, 56 years; 54% women). We used vibration-controlled transient elastography to assess controlled attenuation parameter and liver stiffness measurements as measures of liver steatosis and liver fibrosis, respectively. We assessed noninvasive vascular hemodynamics using arterial tonometry. We assessed cross-sectional relations of vascular hemodynamic measures with continuous and dichotomous measures of hepatic steatosis and fibrosis using multivariable linear and logistic regression., Results: In multivariable models adjusting for cardiometabolic risk factors, higher carotid-femoral pulse wave velocity (estimated β per SD, 0.05 [95% CI, 0.01-0.09]; P =0.003), but not forward pressure wave amplitude and central pulse pressure, was associated with more liver steatosis (higher controlled attenuation parameter). Additionally, higher carotid-femoral pulse wave velocity (β=0.11 [95% CI, 0.07-0.15]; P <0.001), forward pressure wave amplitude (β=0.05 [95% CI, 0.01-0.09]; P =0.01), and central pulse pressure (β=0.05 [95% CI, 0.01-0.09]; P =0.01) were associated with more hepatic fibrosis (higher liver stiffness measurement). Associations were more prominent among men and among participants with obesity, diabetes, and metabolic syndrome (interaction P values, <0.001-0.04). Higher carotid-femoral pulse wave velocity, but not forward pressure wave amplitude and central pulse pressure, was associated with higher odds of hepatic steatosis (odds ratio, 1.16 [95% CI, 1.02-1.31]; P =0.02) and fibrosis (odds ratio, 1.40 [95% CI, 1.19-1.64]; P <0.001)., Conclusions: Elevated aortic stiffness and pressure pulsatility may contribute to hepatic steatosis and fibrosis., Competing Interests: Disclosures G.F. Mitchell is the owner of Cardiovascular Engineering, Inc, a company that designs and manufactures devices that measure vascular stiffness. The company uses these devices in clinical trials that evaluate the effects of diseases and interventions on vascular stiffness. G.F. Mitchell also serves as a consultant to and receives grants and honoraria from Novartis, Merck, Bayer, Servier, Philips, and deCODE genetics and is an inventor on a pending patent application that discloses a method for estimating carotid-femoral pulse wave velocity and vascular age by using a convolutional neural network. M.T. Long is a full-time employee of Novo Nordisk A/S; the data collection and primary analysis were completed while she was employed at Boston University. The other authors report no conflicts.

Background: Among critically ill adults undergoing tracheal intubation, hypoxemia increases the risk of cardiac arrest and death. The effect of preoxygenation with noninvasive ventilation, as compared with preoxygenation with an oxygen mask, on the incidence of hypoxemia during tracheal intubation is uncertain., Methods: In a multicenter, randomized trial conducted at 24 emergency departments and intensive care units in the United States, we randomly assigned critically ill adults (age, ≥18 years) undergoing tracheal intubation to receive preoxygenation with either noninvasive ventilation or an oxygen mask. The primary outcome was hypoxemia during intubation, defined by an oxygen saturation of less than 85% during the interval between induction of anesthesia and 2 minutes after tracheal intubation., Results: Among the 1301 patients enrolled, hypoxemia occurred in 57 of 624 patients (9.1%) in the noninvasive-ventilation group and in 118 of 637 patients (18.5%) in the oxygen-mask group (difference, -9.4 percentage points; 95% confidence interval [CI], -13.2 to -5.6; P<0.001). Cardiac arrest occurred in 1 patient (0.2%) in the noninvasive-ventilation group and in 7 patients (1.1%) in the oxygen-mask group (difference, -0.9 percentage points; 95% CI, -1.8 to -0.1). Aspiration occurred in 6 patients (0.9%) in the noninvasive-ventilation group and in 9 patients (1.4%) in the oxygen-mask group (difference, -0.4 percentage points; 95% CI, -1.6 to 0.7)., Conclusions: Among critically ill adults undergoing tracheal intubation, preoxygenation with noninvasive ventilation resulted in a lower incidence of hypoxemia during intubation than preoxygenation with an oxygen mask. (Funded by the U.S. Department of Defense; PREOXI ClinicalTrials.gov number, NCT05267652.)., (Copyright © 2024 Massachusetts Medical Society.)

Background: The prevalence of many chronic conditions has increased among US adults. Many adults with hypertension have other chronic conditions., Methods: We estimated changes in the age-adjusted prevalence of multiple (≥3) chronic conditions, not including hypertension, using data from the National Health and Nutrition Examination Survey, from 1999-2000 to 2017-2020, among US adults with (n = 24,851) and without (n = 24,337 hypertension. Hypertension included systolic blood pressure (BP) ≥130 mm Hg, diastolic BP ≥80 mm Hg, or antihypertensive medication use. We studied 14 chronic conditions: arthritis, asthma, cancer, coronary heart disease, chronic kidney disease, depression, diabetes, dyslipidemia, hepatitis B, hepatitis C, heart failure, lung disease, obesity, and stroke., Results: From 1999-2000 to 2017-2020, the age-adjusted mean number of chronic conditions increased more among US adults with vs. without hypertension (2.2 to 2.8 vs. 1.7 to 2.0; P-interaction <0.001). Also, the age-adjusted prevalence of multiple chronic conditions increased from 39.0% to 52.0% among US adults with hypertension and from 26.0% to 30.0% among US adults without hypertension (P-interaction = 0.022). In 2017-2020, after age, gender, and race/ethnicity adjustment, US adults with hypertension were 1.94 (95% confidence interval: 1.72-2.18) times as likely to have multiple chronic conditions compared to those without hypertension. In 2017-2020, dyslipidemia, obesity, and arthritis were the most common 3 co-occurring chronic conditions among US adults with and without hypertension (age-adjusted prevalence 16.5% and 3.1%, respectively)., Conclusions: In 2017-2020, more than half of US adults with hypertension had ≥3 additional chronic conditions, a substantial increase from 20 years ago., (© The Author(s) 2024. Published by Oxford University Press on behalf of American Journal of Hypertension, Ltd. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Rheumatoid arthritis(RA) is a condition in which the joints are in a weakly acidic environment. In RA, RA fibroblastlike synoviocytes( RAFLS) in the joints become abnormally activated and secrete a large amount of matrix metalloproteinases(MMPs), and the receptor protein CD44 on the cell membrane is specifically upregulated. Xuetongsu(XTS), an active ingredient in the Tujia ethnomedicine Xuetong, is known to inhibit the proliferation of RAFLS. However, its development and utilization have been limited due to poor targeting ability. A biomimetic XTS-Prussian blue nanoparticles(PB NPs) drug delivery system called THMPX NPs which can target CD44 was constructed in this study. The surface of THMPX NPs was modified with hyaluronic acid(HA) and a long chain of triglycerol monostearate(TGMS) and 3-aminobenzeneboronic acid(PBA)(PBA-TGMS). The overexpressed MMPs and H+ in inflammatory RAFLS can synergistically cleave the PBA-TGMS on the surface of the nanoparticles, exposing HA to interact with CD44. This allows THMPX NPs to accumulate highly in RAFLS, and upon near-infrared light irradiation, generate heat and release XTS, thereby inhibiting the proliferation and migration of RAFLS. Characterization revealed that THMPX NPs were uniform cubes with a diameter of(190. 3±4. 7) nm and an average potential of(-15. 3± 2. 3) m V. Upon near-infrared light irradiation for 5 min, the temperature of THMPX NPs reached 41. 5 ℃, indicating MMPs and H+-triggered drug release. Safety assessments showed that THMPX NPs had a hemolysis rate of less than 4% and exhibited no cytotoxicity against normal RAW264. 7 and human fibroblast-like synoviocytes(HFLS). In vitro uptake experiments demonstrated the significant targeting ability of THMPX NPs to RAFLS. Free radical scavenging experiments revealed excellent free radical clearance capacity of THMPX NPs, capable of removing reactive oxygen species in RAFLS. Cell counting kit-8 and scratch assays demonstrated that THMPX NPs significantly suppressed the viability and migratory ability of RAFLS. This study provides insights into the development of innovative nanoscale targeted drugs from traditional ethnic medicines for RA treatment.

Introduction: The Hispanic population in the US faces a higher risk of nonalcoholic fatty liver disease (NAFLD). Multiple factors influence this risk, including genetics, environmental factors, and socioeconomic statuses. Inadequate access to nutritious foods, or food insecurity, is prevalent among Hispanic individuals and poses a metabolic risk for both the onset and development of NAFLD. Materials and Methods: We utilized the National Health and Nutrition Examination Survey (NHANES) 2017-2020 pre-pandemic data to analyze the association between Hispanic ethnicity, hepatic steatosis, fibrosis, and food insecurity. Vibration-controlled transient elastography (VCTE) was employed to assess liver stiffness (LSM) and controlled attenuation parameter (CAP) scores to determine fibrosis and steatosis, respectively. Linear and ordinal logistic regression models were applied to their continuous, log-transformed, and categorical forms, adjusting for demographics, metabolic comorbidities, and socioeconomic factors. Models were subsequently stratified based on food security statuses. Results: A total of 7396 Hispanic participants were included in the study. Under multivariable analysis, Hispanic individuals had higher CAP scores (Beta-coefficient: 10.2 dB/m, 95% CI: 6.1-14.4 dB/m, p = 0.001)) vs. non-Hispanic individuals, without statistically significant differences in fibrosis. Food-insecure participants exhibited higher CAP scores than their food-secure counterparts. After stratification, a stronger association between Hispanic ethnicity and CAP scores was evident in the food-insecure group (Beta-coefficient: 11.8 dB/m, 95% CI: 4.4-19.3 dB/m, p = 0.003). Discussion: This study demonstrates the heightened risk of hepatic steatosis among individuals with Hispanic ancestry in the US. The risk is exacerbated by food insecurity, particularly for Hispanic individuals. The contribution is linked to the dietary habits in this population that lead to metabolic risk factors associated with hepatic steatosis. Considering the rising prevalence of NAFLD and food insecurity, interventions focusing on nutritional support and healthcare access among this population could mitigate these burdens., Competing Interests: Long and Trivedi have consulted for Novo Nordisk A/S. Long is employed by Novo Nordisk A/S. There are no other conflicts of interest and no other financial disclosures. The sponsors had no role in the design, execution, interpretation, or writing of the study.

Competing Interests: Dr. Umpierrez’s institution received funding from Dexcom, Abbott, Bayer, and Astra Zeneca. Dr. Sirimaturos’ institution received funding from Grifols; he received funding from Astra Zeneca. Dr. Mechanick received funding from Abbott Nutrition, Aveta.Life, and Twin Health. Dr. Irving disclosed that she is an American Society of Parenteral and Enteral Nutrition (ASPEN) board member and author on Society of Critical Care Medicine/ASPEN guidelines for pediatric nutrition support. Dr. Preiser received funding from Edwards, Glysure, Medtronic, and Optiscan. Dr. Krinsley received funding from Dexcom. Dr. Sands received funding from BioXcel Therapeutics. Dr. Jacobi disclosed that she is an Advisory Board Member of the Pfizer Hospital Business Unit. Dr. Agus’ institution received funding from the National Institutes of Health; he disclosed that Dexcom is providing in kind support with continuous glucose monitors for a clinical trial in children. The remaining authors have disclosed that they do not have any potential conflicts of interest.

Objective: Clinical guidelines have expanded the indications for nonalcoholic fatty liver disease (NAFLD) screening to type 2 diabetes mellitus and obesity, which are conditions common in populations who receive care in urban safety-net settings. This study aimed to evaluate safety-net primary care and endocrinology clinicians' knowledge of NAFLD, determine barriers and facilitators to screening, and examine perspectives on the use of electronic health record tools for risk assessment., Methods: Sequential explanatory mixed methods using survey and qualitative interviews with primary care, primary care subspecialty, and endocrinology clinicians in an urban safety-net health care system., Results: A total of 109 participants completed the survey (36.5% response rate), and 13 participated in interviews. Most respondents underestimated or did not know the prevalence of NAFLD (68%), did not use the recommended noninvasive tests for risk stratification (65%), and few were comfortable with screening for (27%) or managing (17%) NAFLD. Endocrinologists had greater knowledge of risk factors but lower rates of comfort and more often felt that screening was not their responsibility. The qualitative themes included the following: (1) lack of knowledge about screening, (2) concern for underdiagnosing NAFLD, (3) perception of severity impacts beliefs about screening, (4) screening should occur in primary care but is not normative practice, (5) concerns exist about benefit, (6) competing demands with a complex population hinder screening, and (7) a need for easier ways to integrate screening into practice., Conclusion: Knowledge gaps may hamper uptake of new guidelines for NAFLD screening in primary care and endocrinology clinics in an urban safety-net health care system. Implementation strategies focused on training and educating clinicians and informed by behavioral economics may increase screening., Competing Interests: Disclosure M.T.L. is a full-time employee of Novo Nordisk but at the time of study completion was not employed by this company. A.M. has received research grants from Gilead Sciences and NASHNET (paid to Boston Medical Center) and has served on an advisory board for Gilead Sciences. The other authors have no conflicts of interest to disclose., (Copyright © 2024 AACE. Published by Elsevier Inc. All rights reserved.)

Purpose of Review: Urea cycle disorders (UCDs) cause elevations in ammonia which, when severe, cause irreversible neurologic injury. Most patients with UCDs are diagnosed as neonates, though mild UCDs can present later - even into adulthood - during windows of high physiologic stress, like critical illness. It is crucial for clinicians to understand when to screen for UCDs and appreciate how to manage these disorders in order to prevent devastating neurologic injury or death., Recent Findings: Hyperammonemia, particularly if severe, causes time- and concentration-dependent neurologic injury. Mild UCDs presenting in adulthood are increasingly recognized, so broader screening in adults is recommended. For patients with UCDs, a comprehensive, multitiered approach to management is needed to prevent progression and irreversible injury. Earlier exogenous clearance is increasingly recognized as an important complement to other therapies., Summary: UCDs alter the core pathway for ammonia metabolism. Screening for mild UCDs in adults with unexplained neurologic symptoms can direct care and prevent deterioration. Management of UCDs emphasizes decreasing ongoing ammonia production, avoiding catabolism, and supporting endogenous and exogenous ammonia clearance. Core neuroprotective and supportive critical care supplements this focused therapy., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

We investigated the interaction between the insect-specific virus, Piura virus (PIUV), and the arbovirus Zika virus (ZIKV) in Aedes albopictus cells. We performed coinfection experiments in C6/36 cells. Piura virus (Cor 33 strain, Colombia) and ZIKV (PRVABC58 strain, Puerto Rico) were co-inoculated into C6/36 cells using two multiplicity of infection (MOI) combinations: 0.1 for both viruses and 1.0 for ZIKV, 0.1 for PIUV. Wells were infected in triplicate with either PIUV and ZIKV coinfection, ZIKV-only, or PIUV-only. Mock infected cells served as control wells. The cell suspension was collected daily 7 days post-infection. Zika virus load was titrated by TCID 50 on Vero 76 cells. The ZIKV-only infection and PIUV and ZIKV coinfection experiments were also quantified by RT-qPCR. We also investigated whether ZIKV interfered in the PIUV replication. PIUV suppressed the replication of ZIKV, resulting in a 10,000-fold reduction in ZIKV titers within 3 days post-infection. PIUV viral loads were not reduced in the presence of ZIKV. We conclude that, when concurrently infected, PIUV suppresses ZIKV in C6/36 cells while ZIKV does not interfere in PIUV replication.

Sarcopenia is associated with NAFLD. It is unknown if the association is explained by shared risk factors. Our study sought to investigate the association between liver fat and sarcopenia in our cohort. Liver fat was measured on CT between 2008 and 2011. We excluded heavy alcohol use and missing covariates. Muscle mass in a subset (n = 485) was measured by 24 h urinary creatinine. Physical function was defined by h strength and walking speed. Sarcopenia was defined as low muscle mass and/or low physical function. We created multivariable-adjusted regression models to evaluate cross-sectional associations between liver fat and low muscle mass, grip strength, and walking speed. The prevalence of hepatic steatosis was 30% (n = 1073; 58.1% women; mean age 65.8 ± 8.6 years). There was a significant positive association between liver fat and muscle mass in linear regression models. The association was not significant after adjusting for BMI. The odds of sarcopenia increased by 28% for each SD in liver fat (OR 1.28; 95% CI 1.02, 1.60) and persisted after accounting for confounders in multivariable-adjusted models (OR 1.30, 95% CI 1.02, 1.67). Further studies are needed to determine if there is a causal relationship between liver fat and sarcopenia and whether treatment of sarcopenia improves liver fat.

Context: Overweight and obesity are associated with relative growth hormone (GH) deficiency, which has been implicated in the development of nonalcoholic fatty liver disease (NAFLD). NAFLD is a progressive disease without effective treatments., Objective: We hypothesized that GH administration would reduce hepatic steatosis in individuals with overweight/obesity and NAFLD., Methods: In this 6-month randomized, double-blind, placebo-controlled trial of low-dose GH administration, 53 adults aged 18 to 65 years with BMI ≥25 kg/m2 and NAFLD without diabetes were randomized to daily subcutaneous GH or placebo, targeting insulin-like growth factor 1 (IGF-1) to the upper normal quartile. The primary endpoint was intrahepatic lipid content (IHL) by proton magnetic resonance spectroscopy (1H-MRS) assessed before treatment and at 6 months., Results: Subjects were randomly assigned to a treatment group (27 GH; 26 placebo), with 41 completers (20 GH and 21 placebo) at 6 months. Reduction in absolute % IHL by 1H-MRS was significantly greater in the GH vs placebo group (mean ± SD: -5.2 ± 10.5% vs 3.8 ± 6.9%; P = .009), resulting in a net mean treatment effect of -8.9% (95% CI, -14.5 to -3.3%). All side effects were similar between groups, except for non-clinically significant lower extremity edema, which was more frequent in the GH vs placebo group (21% vs 0%, P = .02). There were no study discontinuations due to worsening of glycemic status, and there were no significant differences in change in glycemic measures or insulin resistance between the GH and placebo groups., Conclusion: GH administration reduces hepatic steatosis in adults with overweight/obesity and NAFLD without worsening glycemic measures. The GH/IGF-1 axis may lead to future therapeutic targets for NAFLD., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Vitamin C levels are known rapidly decrease in adult critical illness. Vitamin C scavenges free radicals, provides critical protection of the endothelial barrier, and improves endothelial responsiveness to catecholamines. Children with congenital heart disease and undergoing cardiac surgery might be at increased risk for low circulating vitamin C levels. A prospective single-center observational study investigated perioperative changes in vitamin C levels in critically ill Children who underwent congenital heart surgery using CPB. Vitamin C serum levels were collected preoperatively and postoperatively (upon admission to the ICU, 24 and 72 h). Linear mixed-effect model was used to estimate mean circulating concentration of vitamin C and to estimate changes in concentration over time. Primary outcome was change in circulating levels of vitamin C before and after CPB. Secondary outcomes were hospital length of stay (LOS), acute kidney injury (AKI), and illness severity. Forty-one patients with a median age of 4.5 [interquartile range (IQR) 2.6-65.6] months at the time of surgery were consented and enrolled. Median CPB duration was 130 [90-175] minutes, and hospital LOS was 9.1 [5.2-19] days. Mean vitamin C levels (μmol/L) before CPB, at PICU admission, 24 h, and 72 h were 82.0 (95% CI 73.4-90.7), 53.4 (95% CI 44.6,62.0), 55.1 (95% CI 46.3,63.8), and 59.2 (95% CI 50.3,68.1), respectively. Upon postoperative admission to the PICU, vitamin C levels decreased by 28.7 (95% CI 20.6-36.8; p < 0.001) μmol/L, whereas levels at 24 and 72 h recovered and did not differ substantially from concentrations reported upon PICU admission (p > 0.15). Changes in vitamin C concentration were not associated with CPB time, STAT mortality category, age, or PIM3. Three patients had post-CPB hypovitaminosis C or vitamin C deficiency. Reduction in vitamin C levels was not associated with hospital LOS (p = 0.673). A 25 μmol/L decrease in vitamin C levels upon PICU admission was associated with developing AKI (aOR = 3.65; 95% CI 1.01-18.0, p = 0.049). Pediatric patients undergoing cardiac surgery with CPB showed decreased vitamin C levels during the immediate postoperative period. Effects of hypovitaminosis C and vitamin C deficiency in this population remain unclear., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Despite significant advancements in critical care medicine, limited attention has been given to sex and gender disparities in management and outcomes of patients admitted to the intensive care unit (ICU). While "sex" pertains to biological and physiological characteristics, such as reproductive organs, chromosomes and sex hormones, "gender" refers more to sociocultural roles and human behavior. Unfortunately, data on gender-related topics in the ICU are lacking. Consequently, data on sex and gender-related differences in admission to the ICU, clinical course, length of stay, mortality, and post-ICU burdens, are often inconsistent. Moreover, when examining specific diagnoses in the ICU, variations can be observed in epidemiology, pathophysiology, presentation, severity, and treatment response due to the distinct impact of sex hormones on the immune and cardiovascular systems. In this narrative review, we highlight the influence of sex and gender on the clinical course, management, and outcomes of the most encountered intensive care conditions, in addition to the potential co-existence of unconscious biases which may also impact critical illness. Diagnoses with a known sex predilection will be discussed within the context of underlying sex differences in physiology, anatomy, and pharmacology with the goal of identifying areas where clinical improvement is needed. To optimize patient care and outcomes, it is crucial to comprehend and address sex and gender differences in the ICU setting and personalize management accordingly to ensure equitable, patient-centered care. Future research should focus on elucidating the underlying mechanisms driving sex and gender disparities, as well as exploring targeted interventions to mitigate these disparities and improve outcomes for all critically ill patients., (© 2023. The Author(s).)

Background and Aims: While heavy alcohol use consistently associates with liver disease, the effects of nonheavy alcohol consumption are less understood. We aimed to investigate the relationship between nonheavy alcohol use and chronic liver disease., Methods: This cross-sectional study included 2629 current drinkers in the Framingham Heart Study who completed alcohol use questionnaires and transient elastography. We defined fibrosis as liver stiffness measurement (LSM) ≥8.2 kPa. We defined at-risk nonalcoholic steatohepatitis (NASH) as FibroScan-aspartate aminotransferase (FAST) score >0.35 (90% sensitivity) or ≥0.67 (90% specificity). We performed logistic regression to investigate associations of alcohol use measures with fibrosis and NASH, adjusting for sociodemographic and metabolic factors. Subgroup analysis excluded heavy drinkers (>14 drinks per week for women or >21 for men)., Results: In this sample (mean age 54.4 ± 8.9 years, 53.3% women), mean LSM was 5.6 ± 3.4 kPa, 8.2% had fibrosis, 1.9% had NASH by FAST ≥0.67, and 12.4% had NASH by FAST >0.35. Participants drank 6.2 ± 7.4 drinks per week. Total drinks per week and frequency of drinking associated with increased odds of fibrosis (adjusted odds ratio [aOR], 1.18; 95% confidence interval [CI], 1.04-1.33; and aOR, 1.08; 95% CI, 1.01-1.16, respectively). Risky weekly drinking, present in 17.4%, also associated with fibrosis (aOR, 1.49; 95% CI, 1.03-2.14). After excluding 158 heavy drinkers, total drinks per week remained associated with fibrosis (aOR, 1.16; 95% CI, 1.001-1.35). Multiple alcohol use measures positively associated with FAST >0.35., Conclusions: In this community cohort, we demonstrate that nonheavy alcohol use associates with fibrosis and NASH, after adjustment for metabolic factors. Longitudinal studies are needed to determine the benefits of moderating alcohol use to reduce liver-related morbidity and mortality., (Copyright © 2023 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Abstract: Although physical activity (PA) is crucial in the prevention and clinical management of nonalcoholic fatty liver disease, most individuals with this chronic disease are inactive and do not achieve recommended amounts of PA. There is a robust and consistent body of evidence highlighting the benefit of participating in regular PA, including a reduction in liver fat and improvement in body composition, cardiorespiratory fitness, vascular biology, and health-related quality of life. Importantly, the benefits of regular PA can be seen without clinically significant weight loss. At least 150 min of moderate or 75 min of vigorous intensity PA are recommended weekly for all patients with nonalcoholic fatty liver disease, including those with compensated cirrhosis. If a formal exercise training program is prescribed, aerobic exercise with the addition of resistance training is preferred. In this roundtable document, the benefits of PA are discussed, along with recommendations for 1) PA assessment and screening; 2) how best to advise, counsel, and prescribe regular PA; and 3) when to refer to an exercise specialist., (Copyright © 2023 by the American College of Sports Medicine.)

A Vibrio cholerae O1 outbreak emerged in Haiti in October 2022 after years of cholera absence. In samples from a 2021 serosurvey, we found lower circulating antibodies against V. cholerae lipopolysaccharide in children <5 years of age and no vibriocidal antibodies, suggesting high susceptibility to cholera, especially among young children.

Background: With the rising global prevalence of fatty liver disease related to metabolic dysfunction, the association of this common liver condition with chronic kidney disease (CKD) has become increasingly evident. In 2020, the more inclusive term metabolic dysfunction-associated fatty liver disease (MAFLD) was proposed to replace the term non-alcoholic fatty liver disease (NAFLD). The observed association between MAFLD and CKD and our understanding that CKD can be a consequence of underlying metabolic dysfunction support the notion that individuals with MAFLD are at higher risk of having and developing CKD compared with those without MAFLD. However, to date, there is no appropriate guidance on CKD in individuals with MAFLD. Furthermore, there has been little attention paid to the link between MAFLD and CKD in the Nephrology community., Methods and Results: Using a Delphi-based approach, a multidisciplinary panel of 50 international experts from 26 countries reached a consensus on some of the open research questions regarding the link between MAFLD and CKD., Conclusions: This Delphi-based consensus statement provided guidance on the epidemiology, mechanisms, management and treatment of MAFLD and CKD, as well as the relationship between the severity of MAFLD and risk of CKD, which establish a framework for the early prevention and management of these two common and interconnected diseases., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://hbsn.amegroups.com/article/view/10.21037/hbsn-22-421/coif). DCW reports honoraria from Amgen, Astellas, AstraZeneca, Bayer, Boehringer Ingelheim, GlaxoSmithKline, Gilead, Janssen, Mundipharma, Merck Sharp and Dohme, Tricida, Vifor and Zydus. VWSW reports grants from Gilead Sciences; consulting fees from AbbVie, Boehringer Ingelheim, Echosens, Gilead Sciences, Intercept, Inventiva, Novo Nordisk, Pfizer, TARGET PharmaSolutions; honoraria for lectures from Abbott, AbbVie, Gilead Sciences, Novo Nordisk and he is Chairman of Subspecialty Board of Gastroenterology and Hepatology, Hong Kong College of Physicians and Co-founder of Illuminatio Medical Technology Limited. CW reports consulting fees from AstraZeneca, Bayer, Boehringer Ingelheim, Gilead, GSK, MSD, Sanofi; honoraria for lectures from AstraZeneca, Bayer, Boehringer Ingelheim, Eli Lilly. MTL reports research grants from Gilead Sciences and Echosens and he is on Advisory Board of Novo Nordisk. MHN reports research support from Pfizer, Enanta, Gilead, Exact Sciences, Vir Biotech, Helio Health, National Cancer Institute, Glycotest, B.K. Kee Foundation, CurveBio and he is on consulting/advisory Board of Intercept, Exact Science, Gilead, GSK, Eli Lilly, Laboratory of Advanced Medicine. SDN reports consulting fees from ACI clinical, Bayer, Lily, Vifor, Vertex and DSMB: AstraZeneca. JB reports grants from Echosens, Intercept, Inventiva, Siemens; consulting fees from Diafir, Echosens, Intercept, Siemens, BMS, Gilead, Intercept, Pfizer, MSD, Novo Nordisk; honoraria from Echosens, Gilead, Intercept, Siemens. LV reports consulting fees from Gilead, Pfizer, Astra Zeneca, Novo Nordisk, Intercept pharmaceuticals, Diatech Pharmacogenetics, IONIS, Viatris; honoraria from MSD, Gilead, AlfaSigma, AbbVie. YJW reports honoraria from AbbVie and Gilead Science. MEK reports honoraria from AstraZeneca, Roche, MSD, AbbVie, Eva, Mash Premier, Takeda, Organon, AUG, Inspire, HSO, Gilead, Janssen, Intercept, Rameda, Ipsen, Onxeo, MinaPharm, Pharco, Zeta, Alfa Cure, Bayer, Oncoustics, PDC, and Spimaco. SS serves as the unpaid editorial board member of Hepatobiliary Surgery and Nutrition. MP reports he is a shareholder in Perspectum Ltd. AGH reports grants from Novo Nordisk, Gilead, Co-lead PI LEGEND trial Inventiva; consulting fees from Novo Nordisk, Gilead, Echosens and Norgine and Julius Clinical. WKC reports consulting fees from Abbvie, Boehringer Ingelheim and Novo Nordisk; honoraria form Viatris and Hisky Medical. HCP reports honoraria from Intercept, Orphalan, Novo Nordisk, Roche Portugal and EISAI. MHZ reports honoraria from Hisky Medical and serves as an unpaid editorial board member of Hepatobiliary Surgery and Nutrition. The other authors have no conflicts of interest to declare., (2023 Hepatobiliary Surgery and Nutrition. All rights reserved.)

Background and Aims: NAFLD strongly associates with cardiovascular disease (CVD) risk factors; however, the association between NAFLD and incident CVD, CVD-related mortality, incident cancer, and all-cause mortality is unclear., Approach and Results: We included 10,040 participants from the Framingham Heart Study, the Coronary Artery Risk Development in Young Adults Study, and the Multi-ethnic Study of Atherosclerosis to assess the longitudinal association between liver fat (defined on CT) and incident CVD, CVD-related mortality, incident cancer, and all-cause mortality. We performed multivariable-adjusted Cox regression models including age, sex, diabetes, systolic blood pressure, alcohol use, smoking, HDL, triglycerides, and body mass index at baseline or time-varying covariates. The average age was 51.3±3.3 years and 50.6% were women. Hepatic steatosis was associated with all-cause mortality after 12.7 years of mean follow-up when adjusting for baseline CVD risk factors, including body mass index (HR: 1.21, 1.04-1.40); however, the results were attenuated when utilizing time-varying covariates. The association between hepatic steatosis and incident CVD was not statistically significant after we accounted for body mass index in models considering baseline covariates or time-varying covariates. We observed no association between hepatic steatosis and CVD-related mortality or incident cancer., Conclusions: In this large, multicohort study of participants with CT-defined hepatic steatosis, accounting for change in CVD risk factors over time attenuated associations between liver fat and overall mortality or incident CVD. Our work highlights the need to consider concurrent cardiometabolic disease when determining associations between NAFLD and CVD and mortality outcomes., (Copyright © 2023 American Association for the Study of Liver Diseases.)

West Nile virus (WNV) neuroinvasive disease threatens the health and well-being of horses and humans worldwide. Disease in horses and humans is remarkably similar. The occurrence of WNV disease in these mammalian hosts has geographic overlap with shared macroscale and microscale drivers of risk. Importantly, intrahost virus dynamics, the evolution of the antibody response, and clinicopathology are similar. The goal of this review is to provide a comparison of WNV infection in humans and horses and to identify similarities that can be exploited to enhance surveillance methods for the early detection of WNV neuroinvasive disease.

Veno-venous extracorporeal membrane oxygenation (VV-ECMO) is increasingly used to manage severe respiratory failure. Unfortunately, refractory hypoxemia often complicates VV-ECMO support. Both circuit- and patient-related etiologies can drive this, and a structured approach is necessary to diagnose and treat the condition. We present the case of a patient on VV-ECMO for acute respiratory distress syndrome who suffered from several distinct etiologies of refractory hypoxemia over a short timeframe. Frequent recalculation of cardiac output and oxygen delivery enabled early diagnosis and treatment of these conditions. We highlight the need for a structured and oft-repeated approach to this complex problem., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2023 International Anesthesia Research Society.)

Background: Higher diet quality is associated with a lower risk of NAFLD., Objectives: We examined the relationship between diet quality and hepatic fibrosis., Methods: We analyzed cross-sectional associations between 3 a priori diet quality scores-the Dietary Approaches to Stop Hypertension (DASH) score, the Alternative Healthy Eating Index (AHEI), and a modified Mediterranean-style Diet Score (MDS)-and hepatic fat [controlled attenuation parameter (CAP)] and fibrosis [liver stiffness measurement (LSM)] measured by vibration-controlled transient elastography (VCTE) in 2532 Framingham Heart Study (FHS) participants and 3295 participants of the National Health and Nutrition Examination Survey (NHANES)., Results: Higher diet quality scores were associated with lower LSM in both FHS and NHANES after adjustment for demographic and lifestyle factors. Additional adjustment for CAP or BMI attenuated the observed associations. Association strength was similar across all 3 diet quality scores. Fixed-effect meta-analysis demonstrated that, under CAP-adjusted models, the LSM decreases associated with 1-SD increase of the DASH, AHEI, and MDS scores were 2% (95% CI: 0.7%, 3.3%; P = 0.002), 2% (95% CI: 0.7%, 3.3%; P = 0.003), and 1.7% (95% CI: 0.7%, 2.6%; P = 0.001), respectively, whereas in the meta-analysis of BMI-adjusted models, LSM reductions associated with 1-SD increase of the DASH, AHEI, and MDS scores were 2.2% (95% CI: -0.1%, 2.2%; P = 0.07), 1.5% (95% CI: 0.3%, 2.7%; P = 0.02), and 0.9 (95% CI: -0.1%, 1.9%; P = 0.07), respectively., Conclusions: We demonstrated associations of higher diet quality with favorable hepatic fat and fibrosis measures. Our data suggest that a healthy diet may reduce the likelihood of obesity and hepatic steatosis as well as the progression of steatosis to fibrosis., (Copyright © 2023 American Society for Nutrition. All rights reserved.)

Background: Adiposity amplifies the genetic risk of non-alcoholic fatty liver disease (NAFLD)., Aim: We evaluated the association between overweight-years, a cumulative exposure based on the product of the duration and severity of excess body weight (body mass index (BMI) ≥ 25 kg/m 2 ), and genetic risk on liver fat and fibrosis., Methods: This is a longitudinal analysis derived from a prospective cohort of adults in the Framingham Heart Study who underwent genotyping and vibration-controlled-transient-elastography with controlled attenuation parameter. Univariable and multivariable linear and logistic regression analyses were used to assess the association between overweight-years and liver fat and fibrosis. The association between genetic variants of liver fat (PNPLA3, TM6SF2, GCKR) and fibrosis (PNPLA3, TM6SF2, HSD17B13) was also assessed using a polygenic risk score., Results: Our sample included 2478 participants (54% women) with mean age and BMI of 40 (±8.5) years and 26.5(±5.1) kg/m 2 , respectively. The mean follow-up was 14(±0.9) years, and each participant underwent three study visits. The prevalence of NAFLD was 28.3% (n = 700), and 207 (8.4%) had clinically significant fibrosis. In age-, sex- and diabetes-adjusted multivariable analyses, overweight-years (per SD) had a strong association with NAFLD (aOR 3.53 [95% CI: 3.10-4.02], p < 0.001), clinically significant fibrosis (aOR 1.60 [95% CI: 1.40-1.84], p < 0.001) and cirrhosis (aOR 1.81 [95% CI: 1.38-2.37], p < 0.001). High-polygenic risk was significantly associated with liver fat and clinically significant fibrosis (p < 0.05)., Conclusion: Overweight-years is strongly associated with NAFLD and clinically significant fibrosis and combined with polygenic risk may assist in defining the trajectory of NAFLD., (© 2023 John Wiley & Sons Ltd.)

Background: Immune complexing of target antigen to high affinity host antibody is recognized to impact the sensitivity of commercial heartworm antigen tests. Published information describing the effect of heat on interfering canine host antibodies is lacking. Immune complex dissociation (ICD) by heat treatment of serum for samples initially testing negative for heartworm antigen increases sensitivity of commercial antigen tests, particularly for single sex or low adult infection intensities. In this study the stability and nature of the targeted epitope and mechanism of heat ICD were examined., Methods: Canine IgG was isolated using protein-A columns from serum originating from four dogs evaluated after necropsy: one dog with evidence of previously cleared infection and three dogs with confirmed heartworm infections. These dogs were expected to have an excess of antibodies based on negative antigen test and to have no or low antigen optical density, respectively, following heat treatment. Interference of antigen detection on (non-heated) positive serum was evaluated, following 1:1 mixing of antibody/PBS solutions previously heated at 25 °C, 65 °C, 75 °C, 85 °C, 95 °C and 104 °C, compared to positive serum/PBS control measured by optical density using a commercial heartworm antigen ELISA and protein quantification. Live heartworms incubated in media for 72 h provided excretory/secretory antigen for antigen stability studies following heat, endopeptidase digestion and disulfide bond reduction., Results: Mixing antigen-positive heartworm serum with antibody solutions demonstrated a significant inhibition of antigen detection for antibody solutions previously heated at 25 °C and 65 °C relative to positive serum/PBS control. Antigen detection optical density was restored at or above the control when positive serum was mixed with solutions previously heated at 75 °C, 85 °C, 95 °C and 104 °C. Significant changes occurred in protein levels for antibody solutions heated at 75 °C, 85 °C, 95 °C and 104 °C. Relative stability of antigen from live heartworms in culture was demonstrated following heat, chemical and enzymatic treatment., Conclusions: Significant changes in protein levels and antigen binding ability occurred in IgG solutions heated above 65 °C. The findings confirm heat denaturation of antibodies as the suspected mechanism of heat ICD at 104 °C for antigen diagnosis of heartworm. No significant change occurred in antigen detection following heat, chemical or enzymatic digestions supporting a heat-stable linear nature of the epitope., (© 2023. The Author(s).)

Chronic liver disease is a major public health burden worldwide 1 . Although different aetiologies and mechanisms of liver injury exist, progression of chronic liver disease follows a common pathway of liver inflammation, injury and fibrosis 2 . Here we examined the association between clonal haematopoiesis of indeterminate potential (CHIP) and chronic liver disease in 214,563 individuals from 4 independent cohorts with whole-exome sequencing data (Framingham Heart Study, Atherosclerosis Risk in Communities Study, UK Biobank and Mass General Brigham Biobank). CHIP was associated with an increased risk of prevalent and incident chronic liver disease (odds ratio = 2.01, 95% confidence interval (95% CI) [1.46, 2.79]; P < 0.001). Individuals with CHIP were more likely to demonstrate liver inflammation and fibrosis detectable by magnetic resonance imaging compared to those without CHIP (odds ratio = 1.74, 95% CI [1.16, 2.60]; P = 0.007). To assess potential causality, Mendelian randomization analyses showed that genetic predisposition to CHIP was associated with a greater risk of chronic liver disease (odds ratio = 2.37, 95% CI [1.57, 3.6]; P < 0.001). In a dietary model of non-alcoholic steatohepatitis, mice transplanted with Tet2-deficient haematopoietic cells demonstrated more severe liver inflammation and fibrosis. These effects were mediated by the NLRP3 inflammasome and increased levels of expression of downstream inflammatory cytokines in Tet2-deficient macrophages. In summary, clonal haematopoiesis is associated with an elevated risk of liver inflammation and chronic liver disease progression through an aberrant inflammatory response., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Background and Aims: We present findings from the inaugural American College of Sports Medicine (ACSM) International Multidisciplinary Roundtable, which was convened to evaluate the evidence for physical activity as a means of preventing or modifying the course of NAFLD., Approach and Results: A scoping review was conducted to map the scientific literature and identify key concepts, research gaps, and evidence available to inform clinical practice, policymaking, and research. The scientific evidence demonstrated regular physical activity is associated with decreased risk of NAFLD development. Low physical activity is associated with a greater risk for disease progression and extrahepatic cancer. During routine health care visits, all patients with NAFLD should be screened for and counseled about physical activity benefits, including reduction in liver fat and improvement in body composition, fitness, and quality of life. While most physical activity benefits occur without clinically significant weight loss, evidence remains limited regarding the association between physical activity and liver fibrosis. At least 150 min/wk of moderate or 75 min/wk of vigorous-intensity physical activity are recommended for all patients with NAFLD. If a formal exercise training program is prescribed, aerobic exercise with the addition of resistance training is preferred., Conclusions: The panel found consistent and compelling evidence that regular physical activity plays an important role in preventing NAFLD and improving intermediate clinical outcomes. Health care, fitness, and public health professionals are strongly encouraged to disseminate the information in this report. Future research should prioritize determining optimal strategies for promoting physical activity among individuals at risk and in those already diagnosed with NAFLD., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Association for the Study of Liver Diseases.)

Background: Hypoxemia is a common and life-threatening complication during emergency tracheal intubation of critically ill adults. The administration of supplemental oxygen prior to the procedure ("preoxygenation") decreases the risk of hypoxemia during intubation., Research Question: Whether preoxygenation with noninvasive ventilation prevents hypoxemia during tracheal intubation of critically ill adults, compared to preoxygenation with oxygen mask, remains uncertain., Study Design and Methods: The PRagmatic trial Examining OXygenation prior to Intubation (PREOXI) is a prospective, multicenter, non-blinded randomized comparative effectiveness trial being conducted in 7 emergency departments and 17 intensive care units across the United States. The trial compares preoxygenation with noninvasive ventilation versus oxygen mask among 1300 critically ill adults undergoing emergency tracheal intubation. Eligible patients are randomized in a 1:1 ratio to receive either noninvasive ventilation or an oxygen mask prior to induction. The primary outcome is the incidence of hypoxemia, defined as a peripheral oxygen saturation <85% between induction and 2 minutes after intubation. The secondary outcome is the lowest oxygen saturation between induction and 2 minutes after intubation. Enrollment began on 10 March 2022 and is expected to conclude in 2023., Interpretation: The PREOXI trial will provide important data on the effectiveness of noninvasive ventilation and oxygen mask preoxygenation for the prevention of hypoxemia during emergency tracheal intubation. Specifying the protocol and statistical analysis plan prior to the conclusion of enrollment increases the rigor, reproducibility, and interpretability of the trial., Clinical Trial Registration Number: NCT05267652., Competing Interests: Conflicts of Interest and Financial Disclosures: Kevin W. Gibbs MD reports financial support and travel were provided by US Department of Defense. Adit. A. Ginde MD MPH reports financial support was provided by US Department of Defense. Matthew E. Prekker MD MPH reports financial support was provided by US Department of Defense. Kevin P. Seitz MD MSc reports financial support was provided by National Heart Lung and Blood Institute. Susan B. Stempek PA MBA reports financial support was provided by American College of Chest Physicians. Akram Khan MD reports financial support was provided by United Therapeutics Corporation. Akram Khan MD reports financial support was provided by 4D Medicine Ltd. Akram Khan MD reports financial support was provided by Regeneron Pharmaceuticals Inc. Akram Khan MD reports financial support was provided by Roche. Akram Khan MD reports financial support was provided by Dompé pharmaceutical. Jessica A. Palakshappa MD MS reports financial support was provided by National Institute on Aging. Joanne M. Wozniak PA MS reports was provided by American College of Chest Physicians. Matthew C. Exline MD, MPH reports financial support was provided by Abbott Laboratories. Derek W. Russell MD reports financial support was provided by National Heart Lung and Blood Institute. Shekar Ghamande MD reports financial support was provided by US Department of Defense. Ari Moskowitz MD MPH reports financial support was provided by National Heart Lung and Blood Institute. Jill Bastman BSN reports financial support was provided by US Department of Defense. Micah T. Long MD reports financial support was provided by pocket cards. Steven G. Schauer DO MS reports was provided by US Department of Defense. David Janz MD MSc reports financial support was provided by US Department of Defense. Matthew W. Semler MD MSc reports financial support was provided by US Department of Defense. Matthew W. Semler MD MSc reports financial support was provided by National Heart Lung and Blood Institute. Jonathan D. Casey MD MSc reports was provided by US Department of Defense. Jonathan D. Casey MD MSc reports was provided by National Heart Lung and Blood Institute. Jonathan D. Casey MD MSc reports travel was provided by Fisher & Paykel Healthcare Inc. Todd W Rice MD MSc reports a relationship with Cumberland Pharmaceuticals Inc that includes: consulting or advisory and equity or stocks. Derek W. Russell MD reports a relationship with Achieve Life Science Inc that includes: equity or stocks. Matthew W. Semler MD MSc reports a relationship with Baxter International Inc that includes: consulting or advisory.

Objectives: To identify risk factors associated with symptoms of anxiety, depression, and obsessive-compulsive disorder (OCD) among children during the 1st year of the COVID-19 pandemic., Methods: A longitudinal study with three cross-sectional timepoints [April 2020 ( n = 273), October 2020 ( n = 180), and April 2021 ( n = 116)] was conducted at a K-12 public school in Florida. Infection and sero-positivity for SARS-CoV-2 was determined by molecular and serologic approaches. Adjusted odds ratios using mixed effect logistic regression models for symptom-derived indicators of anxiety, depression, and OCD in children in April 2021 are presented; past infection and seropositivity were included in the models., Results: The prevalence of anxiety, depression, or OCD moved from 47.1, to 57.2, to 42.2% across the three timepoints during the study. By endline of the study, in April 2021, non-white children were at higher risk for depression and OCD. Risk for anxiety, depression, and OCD was associated with students who lost a family member due to COVID-19 and who were identified as at-risk in previous timepoints. Rates of SARS-CoV-2 infection and seropositivity were low and not statistically associated with assessed outcomes., Conclusions: In situations like the COVID-19 pandemic, targeted mental health interventions and screenings are needed in children and adolescents, especially among minority children., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 McKune, Acosta, Fujii, Joyce-Beaulieu, Sayeed, Cato, Flaherty, Creasy-Marrazzo, Pu, Kariyawasam, Arukha, Cummings, Long, Maurelli and Nelson.)

We provide here an overview of the state of applied techniques in the estimation of the early period of the postmortem interval (PMI). The biological methods included consist of body cooling, CSF potassium, body cooling combined with CSF potassium, and tissue autolysis. For each method, we present its application in human and veterinary medicine and provide current methodology, strengths, and weaknesses, as well as target areas for improvement. We examine current and future molecular methods as they pertain to DNA and primarily to messenger RNA degradation for the estimation of the PMI, as well as the use of RNA in aging wounds, aging blood stains, and the identification of body fluids. Various types of RNA have different lengths, structures, and functions in cells. These differences in RNAs determine various intrinsic properties, such as their half-lives in cells, and, hence, their decay rate as well as their unique use for specific forensic tests. Future applications and refinements of RNA-based techniques provide opportunities for the use of molecular methods in the estimation of PMI and other general forensic applications.