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Background: The NAFLD decompensation risk score (the Iowa Model) was recently developed to identify patients with nonalcoholic fatty liver disease (NAFLD) at highest risk of developing hepatic events using three variables-age, platelet count, and diabetes., Aims: We performed an external validation of the Iowa Model and compared it to existing non-invasive models., Methods: We included 249 patients with NAFLD at Boston Medical Center, Boston, Massachusetts, in the external validation cohort and 949 patients in the combined internal/external validation cohort. The primary outcome was the development of hepatic events (ascites, hepatic encephalopathy, esophageal or gastric varices, or hepatocellular carcinoma). We used Cox proportional hazards to analyze the ability of the Iowa Model to predict hepatic events in the external validation (https://uihc.org/non-alcoholic-fatty-liver-disease-decompensation-risk-score-calculator). We compared the performance of the Iowa Model to the AST-to-platelet ratio index (APRI), NAFLD fibrosis score (NFS), and the FIB-4 index in the combined cohort., Results: The Iowa Model significantly predicted the development of hepatic events with hazard ratio of 2.5 [95% confidence interval (CI) 1.7-3.9, P < 0.001] and area under the receiver operating characteristic curve (AUROC) of 0.87 (CI 0.83-0.91). The AUROC of the Iowa Model (0.88, CI: 0.85-0.92) was comparable to the FIB-4 index (0.87, CI: 0.83-0.91) and higher than NFS (0.66, CI: 0.63-0.69) and APRI (0.76, CI: 0.73-0.79)., Conclusions: In an urban, racially and ethnically diverse population, the Iowa Model performed well to identify NAFLD patients at higher risk for liver-related complications. The model provides the individual probability of developing hepatic events and identifies patients in need of early intervention., (© 2022 Indian National Association for Study of the Liver. Published by Elsevier B.V. All rights reserved.)

After three years with no confirmed cholera cases in Haiti, an outbreak of Vibrio cholerae O1 emerged in October 2022. Levels of pre-existing antibodies provide an estimate of prior immunologic exposure, reveal potentially relevant immune responses, and set a baseline for future serosurveillance. We analyzed dried blood spots collected in 2021 from a population-weighted representative cross-sectional serosurvey in two communes in the Ouest Department of Haiti. We found lower levels of circulating IgG and IgA antibodies against V. cholerae lipopolysaccharide (LPS, IgG and IgA p<0.0001) in those below 5 years of age compared to those five years and older. Among a subset of patients with higher titers of antibodies, we were unable to detect any functional (vibriocidal) antibodies. In conclusion, the lack of detectable functional antibodies, and age-discordant levels of V. cholerae LPS IgG, suggest that populations in Haiti may be highly susceptible to cholera disease, especially among young children., Competing Interests: Conflict of Interest Disclosures. The authors declare that they have no competing interests.

Cardiothoracic surgical critical care medicine (CT-CCM) is a medical discipline centered on the perioperative care of diverse groups of patients. With an aging demographic and an increase in burden of chronic diseases the utilization of cardiothoracic surgical critical care units is likely to escalate in the coming decades. Given these projections, it is important to assess the state of cardiothoracic surgical intensive care, to develop goals and objectives for the future, and to identify knowledge gaps in need of scientific inquiry. This two-part review concentrates on CT-CCM as its own subspeciality of critical care and cardiothoracic surgery and provides aspirational goals for its practitioners and scientists. In part one, a list of guiding principles and a call-to-action agenda geared towards growth and promotion of CT-CCM are offered. In part two, an evaluation of selected scientific data is performed, identifying gaps in CT-CCM knowledge, and recommending direction to future scientific endeavors.

Cardiothoracic surgical critical care medicine is practiced by a diverse group of physicians including surgeons, anesthesiologists, pulmonologists, and cardiologists. With a wide array of specialties involved, the training of cardiothoracic surgical intensivists lacks standardization, creating significant variation in practice. Additionally, it results in siloed physicians who are less likely to collaborate and advocate for the cardiothoracic surgical critical care subspeciality. Moreover, the current model creates credentialing dilemmas, as experienced by some cardiothoracic surgeons. Through the lens of critical care anesthesiologists, this article addresses the shortcomings of the contemporary cardiothoracic surgical intensivist training standards. First, we describe the present state of practice, summarize past initiatives concerning specific training, outline why standardized education is needed, provide goals of such training standardization, and offer a list of desirable competencies that a trainee should develop to become a successful cardiothoracic surgical intensivist.

Everglades virus (EVEV) is a subtype (II) of Venezuelan equine encephalitis virus (VEEV), endemic in southern Florida, USA. EVEV has caused clinical encephalitis in humans, and antibodies have been found in a variety of wild and domesticated mammals. Over 29,000 Culex cedecei females, the main vector of EVEV, were collected in 2017 from Big Cypress and Fakahatchee Strand Preserves in Florida and pool-screened for the presence of EVEV using reverse transcription real-time polymerase chain reaction. The entire 1 E1 protein gene was successfully sequenced from fifteen positive pools. Phylogenetic analysis showed that isolates clustered, based on the location of sampling, into two monophyletic clades that diverged in 2009. Structural analyses revealed two mutations of interest, A116V and H441R, which were shared among all isolates obtained after its first isolation of EVEV in 1963, possibly reflecting adaptation to a new host. Alterations of the Everglades ecosystem may have contributed to the evolution of EVEV and its geographic compartmentalization. This is the first report that shows in detail the evolution of EVEV in South Florida. This zoonotic pathogen warrants inclusion into routine surveillance given the high natural infection rate in the vectors. Invasive species, increasing urbanization, the Everglades restoration, and modifications to the ecosystem due to climate change and habitat fragmentation in South Florida may increase rates of EVEV spillover to the human population., (© The Author(s) 2022. Published by Oxford University Press.)

The rates of survival with functional recovery for out of hospital cardiac arrest remain unacceptably low. Extracorporeal cardiopulmonary resuscitation (ECPR) quickly resolves the low-flow state of conventional cardiopulmonary resuscitation (CCPR) providing valuable perfusion to end organs. Observational studies have shown an association with the use of ECPR and improved survivability. Two recent randomized controlled studies have demonstrated improved survival with functional neurologic recovery when compared to CCPR. Substantial resources and coordination amongst different specialties and departments are crucial for the successful implementation of ECPR. Standardized protocols, simulation based training, and constant communication are invaluable to the sustainability of a program. Currently there is no standardized protocol for the post-cannulation management of these ECPR patients and, ideally, upcoming studies should aim to evaluate these protocols.

About 35% of all broiler flocks in the United States receive an anticoccidial vaccine, but it is not possible to easily differentiate Eimeria vaccine strains from Eimeria field isolates. Being able to do that would allow using vaccines in a more targeted way. The objective of this study was to collect Eimeria maxima isolates from broiler flocks that received anticoccidial feed additives and flocks that had been vaccinated against coccidia and then test them with a multilocus sequencing typing (MLST) scheme developed for this study. Fecal samples were obtained from commercial broiler flocks in Alabama and Tennessee. Oocyst counts in samples tended to be lower in flocks receiving anticoccidial feed additives and higher in vaccinated flocks. Selected samples were screened for presence of E. maxima by quantitative PCR, and Eimeria spp. composition was investigated by next-generation amplicon sequencing (NGAS) in 37 E. maxima positive samples. Other detected Eimeria spp. besides E. maxima were Eimeria acervulina in 35 samples, Eimeria praecox in 23 samples, Eimeria mitis or Eimeria mivati in 17 samples, and Eimeria necatrix or Eimeria tenella in 10 samples. Six partial E. maxima genes (dnaJ domain containing protein, 70-kDa heat shock protein, prolyl endopeptidase, regulator of chromosome condensation domain containing protein, serine carboxypeptidase, and vacuolar proton-translocating ATPase subunit) of 46 samples were sequenced. The MLST scheme was able to differentiate two vaccines from each other. Three of 17 samples from vaccinated flocks differed from the vaccine used in the flock, while 16 of 29 samples from unvaccinated flocks differed from the vaccine. However, there was also a large number of low-quality, ambiguous chromatograms and negative PCRs for the selected genes. If and when more advanced, possibly next-generation sequencing-based methods will be developed, the genes should be considered as targets.

Background & Aims: Nonalcoholic fatty liver disease (NAFLD) is associated with sugar-sweetened beverage (SSB) consumption in cross-sectional studies. In a prospective cohort, we examined the association of beverage consumption (SSB and diet soda) with incident NAFLD and changes in hepatic fat in the Framingham Heart Study (FHS)., Methods: We conducted a prospective observational study of participants from the FHS Third Generation and Offspring cohorts who participated in computed tomography sub-studies. Participants were classified according to their average SSB or diet soda consumption, which was derived from baseline and follow-up food frequency questionnaires: non-consumers (0-&lt;1/month), occasional consumers (1/month-&lt;1/week), and frequent consumers (≥1/week-≥1/day). Hepatic fat was quantified by the liver fat attenuation measurements on computed tomography scan. The primary dependent variable was incident NAFLD; secondarily, we investigated change in liver fat., Results: The cohorts included 691 Offspring (mean age, 62.8 ± 8.2 years; 57.7% women) and 945 Third Generation participants (mean age, 48.4 ± 6.3 years; 46.6% women). In the Offspring cohort, there was a dose-response relationship with SSB consumption and incident NAFLD. Frequent SSB consumers had 2.53 times increased odds of incident NAFLD compared with non-consumers (95% confidence interval, 1.36-4.7) after multivariable analysis. For Offspring cohort participants, occasional and frequent consumers of SSB had a more adverse increase in liver fat compared with non-consumers., Conclusions: Higher average SSB intake is associated with increase in liver fat over 6 years of follow-up and increased odds of incident NAFLD especially among the older cohort, whereas no consistent association was observed for the younger Third Generation cohort., (Copyright © 2022. Published by Elsevier Inc.)

Background: Studies evaluating alcohol consumption and cardiovascular diseases have shown inconsistent results., Methods: We performed a systematic review of peer-reviewed publications from an extensive query of Ovid MEDLINE, Ovid Embase, Ovid Cochrane Database of Systematic Reviews, Scopus, and Web of Science from database inception to March 2022 for all studies that reported the association between alcohol consumption in terms of quantity (daily or weekly amounts) and type of beverage (wine, beer or spirit) and cardiovascular disease events., Results: The study population included a total of 1,579,435 individuals based on 56 cohorts from several countries. We found that moderate wine consumption defined as 1-4 drinks per week was associated with a reduction in risk for cardiovascular mortality when compared with beer or spirits. However, higher risk for cardiovascular disease mortality was typically seen with heavier daily or weekly alcohol consumption across all types of beverages., Conclusions: It is possible that the observational studies may overestimate the benefits of alcohol for cardiovascular disease outcomes. Although moderate wine consumption is probably associated with low cardiovascular disease events, there are many confounding factors, in particular, lifestyle, genetic, and socioeconomic associations with wine drinking, which likely explain much of the association with wine and reduced cardiovascular disease events. Further prospective study of alcohol and all-cause mortality, including cancer, is needed., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objectives: To provide a standard for total abdominal muscle mass (TAM) quantification on computed tomography (CT) and investigate its association with cardiovascular risk in a primary prevention setting., Methods: We included 3016 Framingham Heart Study participants free of cardiovascular disease (CVD) who underwent abdominal CT between 2002 and 2005. On a single CT slice at the level of L3/L4, we segmented (1) TAM-Area, (2) TAM-Index (= TAM-Area/height) and, (3) TAM-Fraction (= TAM-Area/total cross-sectional CT-area). We tested the association of these muscle mass measures with prevalent and incident cardiometabolic risk factors and incident CVD events during a follow-up of 11.0 ± 2.7 years., Results: In this community-based sample (49% women, mean age: 50.0 ± 10.0 years), all muscle quantity measures were significantly associated with prevalent and incident cardiometabolic risk factors and CVD events. However, only TAM-Fraction remained significantly associated with key outcomes (e.g., adj. OR 0.68 [0.55, 0.84] and HR 0.73 [0.57, 0.92] for incident hypertension and CVD events, respectively) after adjustment for age, sex, body mass index, and waist circumference. Moreover, only higher TAM-Fraction was associated with a lower risk (e.g., adj. OR: 0.56 [0.36-0.89] for incident diabetes versus TAM-Area: adj. OR 1.26 [0.79-2.01] and TAM-Index: 1.09 [0.75-1.58])., Conclusion: TAM-Fraction on a single CT slice at L3/L4 is a novel body composition marker of cardiometabolic risk in a primary prevention setting that has the potential to improve risk stratification beyond traditional measures of obesity., Key Points: • In this analysis of the Framingham Heart Study (n = 3016), TAM-F on a single slice CT was more closely associated with prevalent and incident cardiometabolic risk factors as compared to TAM alone or TAM indexed to body surface area. • TAM-F on a single abdominal CT slice at the level of L3/L4 could serve as a standard measure of muscle mass and improve risk prediction., (© 2022. The Author(s).)

Description: Nonalcoholic fatty liver disease (NAFLD) is well recognized as a leading etiology for chronic liver disease, affecting >25% of the US and global populations. Up to 1 in 4 individuals with NAFLD have nonalcoholic steatohepatitis, which is associated with significant morbidity and mortality due to complications of liver cirrhosis, hepatic decompensation, and hepatocellular carcinoma. Although NAFLD is observed predominantly in persons with obesity and/or type 2 diabetes mellitus, an estimated 7%-20% of individuals with NAFLD have lean body habitus. Limited guidance is available to clinicians on appropriate clinical evaluation in lean individuals with NAFLD, such as for inherited/genetic disorders, lipodystrophy, drug-induced NAFLD, and inflammatory disorders. Emerging data now provide more robust evidence to define the epidemiology, natural history, prognosis, and mortality of lean individuals with NAFLD. Multiple studies have found that NAFLD among lean individuals is associated with increased cardiovascular, liver, and all-cause mortality relative to those without NAFLD. This American Gastroenterological Association Clinical Practice Update provides Best Practice Advice to assist clinicians in evidence-based approaches to the diagnosis, staging, and management of NAFLD in lean individuals., Methods: This expert review was commissioned and approved by the American Gastroenterological Association (AGA) Institute Clinical Practice Updates Committee and the AGA Governing Board to provide timely guidance on a topic of high clinical importance to the AGA membership and underwent internal peer review by the Clinical Practice Updates Committee and external peer review through standard procedures of Gastroenterology. Best Practice Advice Statements BEST PRACTICE ADVICE 1: Lean NAFLD should be diagnosed in individuals with NAFLD and body mass index <25 kg/m 2 (non-Asian race) or body mass index <23 kg/m 2 (Asian race). BEST PRACTICE ADVICE 2: Lean individuals with NAFLD should be evaluated routinely for comorbid conditions, such as type 2 diabetes mellitus, dyslipidemia, and hypertension. BEST PRACTICE ADVICE 3: Lean individuals with NAFLD should be risk stratified for hepatic fibrosis to identify those with advanced fibrosis or cirrhosis. BEST PRACTICE ADVICE 4: Lean individuals in the general population should not undergo routine screening for NAFLD; however, screening should be considered for individuals older than 40 years with type 2 diabetes mellitus. BEST PRACTICE ADVICE 5: NAFLD should be considered in lean individuals with metabolic diseases (such as type 2 diabetes mellitus, dyslipidemia, and hypertension), elevated liver biochemical tests, or incidentally noted hepatic steatosis. BEST PRACTICE ADVICE 6: Clinicians should query patients routinely regarding alcohol consumption patterns in all patients with lean NAFLD. BEST PRACTICE ADVICE 7: In patients with lean NAFLD, other causes of liver disease should be ruled out, including other causes of fatty liver, such as HIV, lipodystrophy, lysosomal acid lipase deficiency, familial hypobetalipoproteinemia, and medication-induced hepatic steatosis (methotrexate, amiodarone, tamoxifen, and steroids). BEST PRACTICE ADVICE 8: Current evidence is inadequate to support routine testing for genetic variants in patients with lean NAFLD. BEST PRACTICE ADVICE 9: Liver biopsy, as the reference standard, should be considered if there is uncertainty regarding contributing causes of liver injury and/or the stage of liver fibrosis. BEST PRACTICE ADVICE 10: Serum indices (NAFLD fibrosis score and Fibrosis-4 score) and imaging techniques (transient elastography and magnetic resonance elastography) may be used as alternatives to liver biopsy for fibrosis staging and patient follow-up. These tests can be performed at the time of diagnosis and repeated at intervals of 6 months to 2 years, depending on fibrosis stage and the patient's response to intervention. BEST PRACTICE ADVICE 11: If noninvasive tests (eg, Fibrosis-4 and NAFLD fibrosis score) are indeterminate, a second noninvasive test (eg, transient elastography or magnetic resonance elastography) should be performed to confirm the stage and prognosis of NAFLD. BEST PRACTICE ADVICE 12: In lean patients with NAFLD, lifestyle intervention, including exercise, diet modification, and avoidance of fructose- and sugar-sweetened drinks, to target a modest weight loss of 3%-5% is suggested. BEST PRACTICE ADVICE 13: Administration of vitamin E may be considered in lean persons with biopsy-confirmed nonalcoholic steatohepatitis, but without type 2 diabetes mellitus or cirrhosis. Oral pioglitazone 30 mg daily may be considered in lean persons with biopsy-confirmed nonalcoholic steatohepatitis without cirrhosis. BEST PRACTICE ADVICE 14: The therapeutic role of glucagon-like peptide-1 agonists and sodium-glucose cotransporter-2 inhibitors in the management of lean NAFLD is not fully defined and requires further investigation. BEST PRACTICE ADVICE 15: Hepatocellular carcinoma surveillance with abdominal ultrasound with or without serum α-fetoprotein twice per year is suggested in patients with lean NAFLD and clinical markers compatible with liver cirrhosis., (Copyright © 2022 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Few data are available on frequency of SARS-CoV-2 infection among very young children in low- to middle-income countries (LMIC), with the studies that are available biased towards higher income countries with low reported infection and seroconversion rates. Between February 2019 and March 2021, 388 dried blood spot (DBS) samples were obtained from 257 children less than 30 months of age as part of a prospective observational cohort study of pregnant women and their infants in Haiti; longitudinal samples were available for 107 children. In a subsequent retrospective analysis, DBS samples were tested by ELISA for antibody targeting the receptor binding domain of the SARS-CoV-2 S1 protein. Over the course of the study, 16·7% of the infants became seropositive. All seropositive samples were collected after March 19, 2020 (the date of the first reported COVID-19 case in Haiti) with the highest hazards measured in August 2020. Sampling date was the only covariate associated with the hazard of seroconversion. Our data provide an estimate of SARS-CoV-2 infection rates among very young children without prior SARS-CoV-2 exposure during the initial pandemic waves in Haiti, and demonstrate that these children mount a detectable serological response which is independent of patient age., Competing Interests: The authors have declared that no competing interests exist.

Context: Obesity is a state of relative growth hormone (GH) deficiency, and GH has been identified as a candidate disease-modifying target in nonalcoholic fatty liver disease (NAFLD) because of its lipolytic and anti-inflammatory properties. However, the GH/IGF-1 axis has not been well characterized in NAFLD., Objective: We aimed to investigate serum GH and IGF-1 levels in relation to intrahepatic lipid content (IHL) and markers of hepatocellular damage and fibrosis in NAFLD., Methods: This cross-sectional study included 102 adults (43% women; age 19-67; BMI ≥ 25 kg/m2) without type 2 diabetes. IHL was measured by magnetic resonance spectroscopy; NAFLD was defined by ≥ 5% IHL. Peak-stimulated GH in response to GH releasing hormone and arginine was assessed as was serum IGF-1 (LC/MS)., Results: There was no difference in mean age, BMI, or sex distribution in NAFLD vs controls. Mean (± SD) IHL was higher in NAFLD vs controls (21.8 ± 13.3% vs 2.9 ± 1.1%, P < 0.0001). Mean peak-stimulated GH was lower in NAFLD vs controls (9.0 ± 6.3 vs 15.4 ± 11.2 ng/mL, P = 0.003), including after controlling for age, sex, visceral adipose tissue, and fasting glucose. In a stepwise model, peak-stimulated GH predicted 14.6% of the variability in IHL (P = 0.004). Higher peak-stimulated GH was also associated with lower ALT. Higher serum IGF-1 levels were associated with lower risk of liver fibrosis by Fibrosis-4 scores., Conclusion: Individuals with NAFLD have lower peak-stimulated GH levels but similar IGF-1 levels as compared to controls. Higher peak-stimulated GH levels are associated with lower IHL and less hepatocellular damage. Higher IGF-1 levels are associated with more favorable fibrosis risk scores. These data implicate GH and IGF-1 as potential disease modifiers in the development and progression of NAFLD., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Hyperammonemia occurs frequently in the critically ill but is largely confined to patients with hepatic dysfunction or failure. Non-hepatic hyperammonemia (NHHA) is far less common but can be a harbinger of life-threatening diagnoses that warrant timely identification and, sometimes, empiric therapy to prevent seizures, status epilepticus, cerebral edema, coma and death; in children, permanent cognitive impairment can result. Subsets of patients are at particular risk for developing NHHA, including the organ transplant recipient. Unique etiologies include rare infections, such as with Ureaplasma species, and unmasked inborn errors of metabolism, like urea cycle disorders, must be considered in the critically ill. Early recognition and empiric therapy, including directed therapies towards these rare etiologies, is crucial to prevent catastrophic demise. We review the etiologies of NHHA and highlight the first presentation of it associated with a concurrent Ureaplasma urealyticum and Mycoplasma hominis infection in a previously healthy individual with polytrauma. Based on this clinical review, a diagnostic and treatment algorithm to identify and manage NHHA is proposed., Competing Interests: Declaration of Competing Interest None., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Because of the trend of cage-free egg production, infections with the nematode Ascaridia galli are receiving increased attention. The aim of this study was to establish a timeline for the influence of A. galli on the expression of key cytokines related to a parasitic immune response, and on the composition of the jejunal microbiota. Twenty-eight male layer-type birds were challenged at 24, 25, and 26 days of age. An additional 28 birds were kept as uninfected controls. Starting on Day 31, three birds of each group were euthanized every week until 8 wk postinfection (PI). The number of larvae isolated from the intestinal wall decreased over time, until no larvae were seen at 7 and 8 wk PI. At 5 wk PI, there was a numerical upregulation of all cytokines (TGF-β, IFN-γ, IL-4, IL-8, IL-10, IL-13) in the infected group, but this change was only statistically significant for IL-13. At this time point, larvae were expected to have developed into adults that would have shed eggs in the feces. However, no adult worms were seen and there was no egg shedding. For the microbiota analysis, there were significant differences in the alpha diversity (Faith's phylogenetic diversity) between challenge and control groups, and the beta diversity analysis showed slight differences between samples, suggesting that the age of the birds was the main reason for the separation of groups. These findings suggest that the upregulation of all cytokines evaluated in Week 5 might be the reason for resolution of the infection. Possible explanations are that a high infection dose and the fact that birds were fed with a more nutritionally dense feed might have contributed to the birds' immune system clearing the infection before the worms were able to reach maturity.

Nonalcoholic fatty liver disease (NAFLD) is a growing cause of chronic liver disease. Using a proxy NAFLD definition of chronic elevation of alanine aminotransferase (cALT) levels without other liver diseases, we performed a multiancestry genome-wide association study (GWAS) in the Million Veteran Program (MVP) including 90,408 cALT cases and 128,187 controls. Seventy-seven loci exceeded genome-wide significance, including 25 without prior NAFLD or alanine aminotransferase associations, with one additional locus identified in European American-only and two in African American-only analyses (P < 5 × 10 -8 ). External replication in histology-defined NAFLD cohorts (7,397 cases and 56,785 controls) or radiologic imaging cohorts (n = 44,289) replicated 17 single-nucleotide polymorphisms (SNPs) (P < 6.5 × 10 -4 ), of which 9 were new (TRIB1, PPARG, MTTP, SERPINA1, FTO, IL1RN, COBLL1, APOH and IFI30). Pleiotropy analysis showed that 61 of 77 multiancestry and all 17 replicated SNPs were jointly associated with metabolic and/or inflammatory traits, revealing a complex model of genetic architecture. Our approach integrating cALT, histology and imaging reveals new insights into genetic liability to NAFLD., (© 2022. This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.)

Objective: The infant lumbar puncture (LP) can be a technically challenging procedure. Understanding the anatomical lumbar dimensions may optimize LP conditions. Data from preterm neonates, older children, and adults indicate measurements of the lumbar spine in the seated LP position may be superior when compared with the lateral position. We use point-of-care ultrasound (US) to determine if the seated position, when compared with the lateral decubitus position, significantly affected the lumbar dimensions of infants 12 months or younger presenting to the pediatric emergency department., Methods: We conducted a prospective observational study of a convenience sample of patients 12 months or younger. We used US to obtain 3 still images oriented longitudinally in the midline over the L3 to L4 interspace in the lateral decubitus and seated positions. A US fellowship-trained emergency physician, blinded to patient position, measured interspinous space, subarachnoid space width, and spinal canal depth. We then compared the means of all 3 dimensions in the lateral and seated positions., Results: From 50 subjects, 49 subjects provided 46 evaluable sets of images for each measure. Interspinous space, spinal canal depth, and subarachnoid space width did not differ significantly between positions. Mean differences did not exceed 0.02 cm for any of the measured dimensions. We report no significant differences in the 3 lumbar dimensions at the seated position when compared with the lateral decubitus position., Conclusions: For infants younger than 12 months, sonographic measurements of lumbar dimensions did not differ between the positions commonly used for LP., Competing Interests: Disclosure: The authors declare no conflict of interest., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

A young adult female presented with hypotension and depressed mental status after intentional overdose of Amlodipine. After intubation and institution of lung-protective mechanical ventilation, initial management focused on maintenance of a mean arterial blood pressure over 65 mmHg and included fluid resuscitation (eight liters of crystalloid), Insulin and dextrose, intravenous calcium and, finally, vasopressor support. Her course was complicated by hypoxia due to non-cardiogenic pulmonary edema requiring diuresis. She was extubated soon thereafter but developed severe hypoxia within 72 hours requiring re-intubation. A subsequent bronchoscopy demonstrated diffuse alveolar hemorrhage (DAH). This is the first report of DAH complicating amlodipine overdose., Competing Interests: There are no conflicts of interest., (Copyright: © 2022 Saudi Journal of Anesthesia.)

Background: Frailty is an important contributor to morbidity and mortality in chronic liver disease. Understanding the contributors to frailty has the potential to identify individuals at risk for frailty and may potentially provide targets for frailty-modifying interventions. We evaluated the relationship among cognitive function, inflammation, and sarcopenia and frailty., Methods: Using cohorts from the Framingham Heart Study (2011-2014), we evaluated for factors associated with frailty. Exposures included cognitive tests (combined Trails A/B test, Animal Naming Test, and combined Digit Span Forward/Backward test), inflammation (interleukin-6 and tumor necrosis factor receptor II), and sarcopenia (creatinine-to-cystatin C ratio). We performed linear and logistic regression to identify the relationship between these exposures and the Liver Frailty Index (LFI)., Results: The study population (N = 1208) had a median age of 70 years, was 56% female, and 48.5% had evidence of liver disease. The combined Trails A/B test (β 0.05, P < .001), creatinine-to-cystatin C (β -0.17, P = .006), and both inflammatory markers, interleukin-6 levels (β 0.16, P = .002) and tumor necrosis factor receptor II (β 0.21, P = .04), were independently associated with the LFI. Using an LFI cutoff of ≥4.5 to define frailty, Trails A/B (odds ratio [OR] 1.21, 95% confidence interval [CI] 1.07-1.37), Animal Naming Test (OR 0.64, 95% CI 0.42-0.97), sarcopenia (OR 0.10, 95% CI 0.01-0.73), and interleukin-6 (OR 4.99, 95% CI 1.03-15.53) were all associated with frailty. Although liver disease did not modify the relationship between the LFI and the Trails A/B test, interleukin-6 was significantly associated with the LFI only in the presence of liver disease., Conclusions: Cognitive performance, inflammation, and sarcopenia, each highly prevalent in cirrhosis, are associated with the LFI in this population-based study of persons without cirrhosis. Further research is warranted for interventions aiming to prevent frailty by tailoring their approach to the patient's underlying risk factors., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Estimation of the postmortem interval (PMI) is a poorly studied field in veterinary pathology. The development of field-applicable methods is needed given that animal cruelty investigations are increasing continually. We evaluated various histologic criteria in equine brain, liver, and muscle tissue to aid the estimation of PMI in horses, which is central to forensic investigations of suspicious death. After death, autolysis proceeds predictably, depending on environmental conditions. Currently, no field-applied methods exist that accurately estimate the PMI using histology in animals or humans through quantification of autolysis. Brain, liver, and skeletal muscle from 12 freshly euthanized horses were held at 22°C and 8°C for 72 h. Tissues were sampled at T0h, T1h, T2h, T4h, T6h, T12h, T24h, T36h, T48h, T60h, and T72h. For each tissue, we quantified 5 to 7 criteria associated with autolysis, based on the percentage of microscopic field involved. Each criterion was modeled, with temperature and time as independent variables. Changes were most predictable in liver and muscle over the first 72 h postmortem. The criteria for autolysis that were present most extensively at both temperatures were hepatocyte individualization and the separation of bile duct epithelium from the basement membrane. The changes that were present next most extensively were disruption of myofiber continuity, hypereosinophilia, and loss of striation. Brain changes were highly variable. The high statistical correlation between the parameter "autolysis" and the variables "time/temperature", indicates that autolysis is progressive and predictable. Further investigation of these criteria is needed to establish histologic algorithms for PMI.

Long MT, Grate J, Bradley KV. Postoperative Hemidiaphragmatic Paralysis and Platypnea-Orthodeoxia Syndrome. Indian J Crit Care Med 2021;25(8):951-953., Competing Interests: Source of support: Nil Conflict of interest: None, (Copyright © 2021; Jaypee Brothers Medical Publishers (P) Ltd.)

Background Obesity may be associated with a range of cardiometabolic manifestations. We hypothesized that proteomic profiling may provide insights into the biological pathways that contribute to various obesity-associated cardiometabolic traits. We sought to identify proteomic signatures of obesity and examine overlap with related cardiometabolic traits, including abdominal adiposity, insulin resistance, and adipose depots. Methods and Results We measured 71 circulating cardiovascular disease protein biomarkers in 6981 participants (54% women; mean age, 49 years). We examined the associations of obesity, computed tomography measures of adiposity, cardiometabolic traits, and incident metabolic syndrome with biomarkers using multivariable regression models. Of the 71 biomarkers examined, 45 were significantly associated with obesity, of which 32 were positively associated and 13 were negatively associated with obesity (false discovery rate q <0.05 for all). There was significant overlap of biomarker profiles of obesity and cardiometabolic traits, but 23 biomarkers, including melanoma cell adhesion molecule (MCAM), growth differentiation factor-15 (GDF15), and lipoprotein(a) (LPA) were unique to metabolic traits only. Using hierarchical clustering, we found that the protein biomarkers clustered along 3 main trait axes: adipose, metabolic, and lipid traits. In longitudinal analyses, 6 biomarkers were significantly associated with incident metabolic syndrome: apolipoprotein B (apoB), insulin-like growth factor-binding protein 2 (IGFBP2), plasma kallikrein (KLKB1), complement C2 (C2), fibrinogen (FBN), and N-terminal pro-B-type natriuretic peptide (NT-proBNP); false discovery rate q <0.05 for all. Conclusions We found that the proteomic architecture of obesity overlaps considerably with associated cardiometabolic traits, implying shared pathways. Despite overlap, hierarchical clustering of proteomic profiles identified 3 distinct clusters of cardiometabolic traits: adipose, metabolic, and lipid. Further exploration of these novel protein targets and associated pathways may provide insight into the mechanisms responsible for the progression from obesity to cardiometabolic disease.

Background and Aims: Electronic health record (EHR)-based research allows the capture of large amounts of data, which is necessary in NAFLD, where the risk of clinical liver outcomes is generally low. The lack of consensus on which International Classification of Diseases (ICD) codes should be used as exposures and outcomes limits comparability and generalizability of results across studies. We aimed to establish consensus among a panel of experts on ICD codes that could become the reference standard and provide guidance around common methodological issues., Approach and Results: Researchers with an interest in EHR-based NAFLD research were invited to collectively define which administrative codes are most appropriate for documenting exposures and outcomes. We used a modified Delphi approach to reach consensus on several commonly encountered methodological challenges in the field. After two rounds of revision, a high level of agreement (>67%) was reached on all items considered. Full consensus was achieved on a comprehensive list of administrative codes to be considered for inclusion and exclusion criteria in defining exposures and outcomes in EHR-based NAFLD research. We also provide suggestions on how to approach commonly encountered methodological issues and identify areas for future research., Conclusions: This expert panel consensus statement can help harmonize and improve generalizability of EHR-based NAFLD research., (© 2021 The Authors. HEPATOLOGY published by Wiley Periodicals LLC on behalf of American Association for the Study of Liver Diseases.)

Background and Aims: Portal pressure can be used to identify patients with chronic liver disease who have progressed to cirrhosis. Portal pressure can also provide accurate prognostication for patients with cirrhosis. However, there are no practical means for assessment of portal pressure. Although it is well established that the gastric mucosal blood supply increases in patients with cirrhosis, this has been difficult to quantify reproducibly. Our group has developed a novel spectroscopic technology called spatially resolved subdiffuse reflectance spectroscopy (SRSRS), which enables quantification of mucosal microcirculation. We aim to ascertain if quantification of the gastric mucosal microcirculation with SRSRS correlates with clinical evidence of portal hypertension., Methods: Patients undergoing EGD for clinical indications had 10 measurements taken in the endoscopically normal gastric fundus via SRSRS probe to assess the microcirculation. Cases were defined as patients with cirrhosis (n = 18), and controls were those without evidence of liver disease (n = 18); this was corroborated with transient elastography., Results: The blood volume fraction (P = .06) and subdiffuse reflectance (P = .02) from a shallow depth in the gastric fundus were higher in patients with cirrhosis than those without. These markers were combined to yield an overall optical marker that can differentiate patients with cirrhosis from controls with a sensitivity of 72% and specificity of 94% (area under receiver operating curve, 0.82)., Conclusions: Spectroscopic quantification of gastric fundal mucosal microcirculation is a promising surrogate of clinical correlates of portal hypertension. This approach may represent a less-intrusive surrogate biomarker for liver disease prognostication and potentially response to therapy., (Copyright © 2021 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

The composition of wildlife communities can have strong effects on transmission of zoonotic vector-borne pathogens, with more diverse communities often supporting lower infection prevalence in vectors (dilution effect). The introduced Burmese python, Python bivittatus, is eliminating large and medium-sized mammals throughout southern Florida, USA, impacting local communities and the ecology of zoonotic pathogens. We investigated invasive predator-mediated impacts on ecology of Everglades virus (EVEV), a zoonotic pathogen endemic to Florida that circulates in mosquito-rodent cycle. Using binomial generalized linear mixed effects models of field data at areas of high and low python densities, we show that increasing diversity of dilution host (non-rodent mammals) is associated with decreasing blood meals on amplifying hosts (cotton rats), and that increasing cotton rat host use is associated with increasing EVEV infection in vector mosquitoes. The Burmese python has caused a dramatic decrease in mammal diversity in southern Florida, which has shifted vector host use towards EVEV amplifying hosts (rodents), resulting in an indirect increase in EVEV infection prevalence in vector mosquitoes, putatively elevating human transmission risk. Our results indicate that an invasive predator can impact wildlife communities in ways that indirectly affect human health, highlighting the need for conserving biological diversity and natural communities.

A 49-year-old man with cirrhosis and portal hypertension was admitted for acute respiratory distress syndrome secondary to coronavirus disease 2019 (COVID-19) pneumonia. His course was complicated by postprandial hypotension (PPH)-episodic hemodynamic collapse that occurred minutes after enteral administration of medications or fluids. Octreotide, which reduces splanchnic pooling and can treat PPH, successfully prevented ongoing events. PPH is associated with mortality in the outpatient setting, and at-risk patients include the elderly and those with autonomic dysfunction, including those with COVID-19. Portal hypertension is a likely additional risk factor that has not been previously described. Octreotide is the mainstay of PPH prophylaxis., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2021 International Anesthesia Research Society.)

Background Men and women are labeled as obese on the basis of a body mass index (BMI) using the same criterion despite known differences in their fat distributions. Subcutaneous adipose tissue and visceral adipose tissue (VAT), as measured by computed tomography, are advanced measures of obesity that closely correlate with cardiometabolic risk independent of BMI. However, it remains unknown whether prognostic significance of anthropometric measures of adiposity versus VAT varies in men versus women. Methods and Results In 3482 FHS (Framingham Heart Study) participants (48.1% women; mean age, 50.8±10.3 years), we tested the associations of computed tomography-based versus anthropometric measures of fat with cardiometabolic and cardiovascular disease (CVD) risk. Mean follow-up was 12.7±2.1 years. In men, VAT, as compared with BMI, had a similar strength of association with incident cardiometabolic risk factors (eg, adjusted odds ratio [OR], 2.36 [95% CI, 1.84-3.04] versus 2.66 [95% CI, 2.04-3.47] for diabetes mellitus) and CVD events (eg, adjusted hazard ratio [HR], 1.32 [95% CI, 0.97-1.80] versus 1.74 [95% CI, 1.14-2.65] for CVD death). In women, however, VAT, when compared with BMI, conferred a markedly greater association with incident cardiometabolic risk factors (eg, adjusted OR, 4.51 [95% CI, 3.13-6.50] versus 2.33 [95% CI, 1.88-3.04] for diabetes mellitus) as well as CVD events (eg, adjusted HR, 1.85 [95% CI, 1.26-2.71] versus 1.19 [95% CI, 1.01-1.40] for CVD death). Conclusions Anthropometric measures of obesity, including waist circumference and BMI, adequately capture VAT-associated cardiometabolic and cardiovascular risk in men but not in women. In women, abdominal computed tomography-based VAT measures permit more precise assessment of obesity-associated cardiometabolic and cardiovascular risk.

Background: Metabolic syndrome increases adverse outcomes in coronavirus disease 2019 (COVID-19) infection. Hepatic steatosis may increase risk of COVID-19 severity. Current studies evaluating steatosis lack reliable definitions. We aimed to evaluate the association of radiographic hepatic steatosis and clinical outcomes of COVID-19 severity in a diverse cohort., Methods: We retrospectively identified patients with COVID-19 infection admitted to two US academic hospitals. Outcomes were length of stay, intensive care unit use, mechanical ventilation, and in-hospital mortality. We used Mann-Whitney U-test for continuous measures and Chi-square or Fisher's exact test for categorical measures. Multivariable linear and logistic regression analyses were used to adjust for confounders., Results: Of the 319 patients, 14% had hepatic steatosis. There were no differences in length of stay (6 (4 - 16) vs. 9 (4 - 18) days, P = 0.6), intensive care unit (24% vs. 32%, P = 0.3), mechanical ventilation (28% vs. 38%, P = 0.32), or in-hospital mortality (7% vs. 17%, P = 0.12). After adjustment, there was no difference in length of stay (β: -14.37, 95% confidence interval (CI): -30.5 - 1.77, P = 0.08), intensive care unit (odds ratio (OR): 0.31, 95% CI: 0.03 - 1.09, P = 0.06), mechanical ventilation (OR: 0.13, 95% CI: 0.02 - 1.09, P = 0.06), or in-hospital mortality (OR: 0.27, 95% CI: 0.06 - 1.16, P = 0.08) among patients with hepatic steatosis., Conclusion: Radiographic hepatic steatosis was not associated with worse outcomes among patients hospitalized with COVID-19., Competing Interests: None to declare., (Copyright 2021, Trivedi et al.)

The group of Insect-specific viruses (ISVs) includes viruses apparently restricted to insects based on their inability to replicate in the vertebrates. Increasing numbers of ISVs have been discovered and characterized representing a diverse number of viral families. However, most studies have focused on those ISVs belonging to the family Flaviviridae, which highlights the importance of ISV study from other viral families, which allow a better understanding for the mechanisms of transmission and evolution used for this diverse group of viruses. Some ISVs have shown the potential to modulate arboviruses replication and vector competence of mosquitoes. Based on this, ISVs may be used as an alternative tool for biological control, development of vaccines, and diagnostic platforms for arboviruses. In this review, we provide an update of the general characteristics of ISVs and their interaction with arboviruses that infect vertebrates., (Copyright © 2021. Published by Elsevier Inc.)

Osteoporosis, a disease characterized by low bone mineral density (BMD), increases the risk for fractures. Conventional risk factors alone do not completely explain measured BMD or osteoporotic fracture risk. Metabolomics may provide additional information. We aim to identify BMD-associated metabolomic markers that are predictive of fracture risk. We assessed 209 plasma metabolites by liquid chromatography with tandem mass spectrometry (LC-MS/MS) in 1552 Framingham Offspring Study participants, and measured femoral neck (FN) and lumbar spine (LS) BMD 2 to 10 years later using dual-energy X-ray absorptiometry. We assessed osteoporotic fractures up to 27-year follow-up after metabolomic profiling. We identified 27 metabolites associated with FN-BMD or LS-BMD by LASSO regression with internal validation. Incorporating selected metabolites significantly improved the prediction and the classification of osteoporotic fracture risk beyond conventional risk factors (area under the curve [AUC] = 0.74 for the model with identified metabolites and risk factors versus AUC = 0.70 with risk factors alone, p = .001; net reclassification index = 0.07, p = .03). We replicated significant improvement in fracture prediction by incorporating selected metabolites in 634 participants from the Hong Kong Osteoporosis Study (HKOS). The glycine, serine, and threonine metabolism pathway (including four identified metabolites: creatine, dimethylglycine, glycine, and serine) was significantly enriched (false discovery rate [FDR] p value = .028). Furthermore, three causally related metabolites (glycine, phosphatidylcholine [PC], and triacylglycerol [TAG]) were negatively associated with FN-BMD, whereas PC and TAG were negatively associated with LS-BMD through Mendelian randomization analysis. In summary, metabolites associated with BMD are helpful in osteoporotic fracture risk prediction. Potential causal mechanisms explaining the three metabolites on BMD are worthy of further experimental validation. Our findings may provide novel insights into the pathogenesis of osteoporosis. © 2021 American Society for Bone and Mineral Research (ASBMR)., (© 2021 American Society for Bone and Mineral Research (ASBMR).)

Arthropod-borne viruses (arboviruses) are global pathogens circulating endemically with local explosive outbreaks and constant encroachment into new locations. Few vaccines against arboviruses exist; most for humans are in development or clinical trials. Insect-specific viruses (ISVs) offer a unique platform for expression of arbovirus proteins, through the creation of ISV/arbovirus chimeras. Studies have shown promising results of these vaccines with several advantages over their wild-type counterparts. In this review, we discuss the current status of these potential vaccines using ISVs.

Introduction: The proportion of women editorial board members and authors of editorials in major gastroenterology journals is not known., Methods: We determined the sex of editorial board members (n = 2,282) and authors of editorials (n = 1,705) across 6 journals from 1985 to 2020 at 5-year intervals., Results: The proportion of women editorial board members increased from 2.9% in 1985 to 19.8% in 2020 (P < 0.0001) and women authors of editorials increased from 0% in 1985 to 22.2% in 2020 (P < 0.0001)., Discussion: The proportion of women represented over time has improved, but opportunities likely exist to improve further., (Copyright © 2021 by The American College of Gastroenterology.)

Objective: Nonalcoholic fatty liver disease (NAFLD) is associated with low bone mineral density (BMD); however, it is not known whether early-stage NAFLD may be associated with BMD after accounting for BMI or visceral adipose tissue (VAT)., Methods: This was a cross-sectional study of 3,462 Framingham Heart Study participants who underwent computed tomographic measurement of liver fat, VAT volume, volumetric spine BMD, vertebral cross-sectional area (CSA), and vertebral compressive strength. This study excluded heavy alcohol consumers. Multivariable linear regression models were used to assess the association between NAFLD and volumetric BMD, CSA, and vertebral compressive strength after accounting for covariates, including BMI or VAT., Results: A total of 2,253 participants (mean age, 51.2  [SD 10.7] years; 51.1% women) were included. In multivariable-adjusted models, positive associations between NAFLD and integral BMD, trabecular BMD, and vertebral compressive strength were observed. However, results were attenuated and no longer significant after additionally adjusting for BMI or VAT. NAFLD was observed to be weakly associated with a lower vertebral CSA in adjusted models., Conclusions: In a community-based cohort, the associations between NAFLD and BMD and vertebral strength were confounded by BMI and VAT. However, NAFLD was associated with a reduced vertebral CSA in adjusted models., (© 2021 The Obesity Society.)

Background and Aims: NAFLD is increasing in prevalence and will soon be the most common chronic liver disease. Liver stiffness, as assessed by vibration-controlled transient elastography (VCTE), correlates with hepatic fibrosis, an important predictor of liver-related and all-cause mortality. Although liver fat is associated with cardiovascular risk factors, the association between hepatic fibrosis and cardiovascular risk factors is less clear., Approach and Results: We performed VCTE, assessing controlled attenuation parameter (CAP; measure of steatosis) and liver stiffness measurement (LSM) in 3,276 Framingham Heart Study adult participants (53.9% women, mean age 54.3 ± 9.1 years) presenting for a routine study visit. We performed multivariable-adjusted logistic regression models to determine the association between LSM and obesity-related, vascular-related, glucose-related, and cholesterol-related cardiovascular risk factors. The prevalence of hepatic steatosis (CAP ≥ 290 dB/m) was 28.8%, and 8.8% had hepatic fibrosis (LSM ≥ 8.2 kPa). Hepatic fibrosis was associated with multiple cardiovascular risk factors, including increased odds of obesity (OR, 1.82; 95% CI, 1.35-2.47), metabolic syndrome (OR, 1.49; 95% CI 1.10-2.01), diabetes (OR, 2.67; 95% CI, 1.21-3.75), hypertension (OR, 1.52; 95% CI, 1.15-1.99), and low high-density lipoprotein cholesterol (OR, 1.47; 95% CI, 1.09-1.98), after adjustment for age, sex, smoking status, alcohol drinks/week, physical activity index, aminotransferases, and CAP., Conclusions: In our community-based cohort, VCTE-defined hepatic fibrosis was associated with multiple cardiovascular risk factors, including obesity, metabolic syndrome, diabetes, hypertension, and high-density lipoprotein cholesterol, even after accounting for covariates and CAP. Additional longitudinal studies are needed to determine if hepatic fibrosis contributes to incident cardiovascular disease risk factors or events., (© 2020 by the American Association for the Study of Liver Diseases.)

Background: Detection of Dirofilaria immitis, or heartworm, through antigen in sera is the primary means of diagnosing infections in dogs. In recent years, the practice of heat-treating serum prior to antigen testing has demonstrated improved detection of heartworm infection. While the practice of heat-treating serum has resulted in earlier detection and improved sensitivity for heartworm infections, it has been suggested that heat treatment may cause cross reactivity with A. reconditum and intestinal helminth infections of dogs. No studies have assessed the potential cross-reactivity of these parasites with heartworm tests before and after heat treatment using blood products and an appropriate gold standard reference., Methods: Canine sera (n=163) was used to evaluate a heartworm antigen-ELISA (DiroCHEK®) and potential cross-reactivity with common parasitic infections. The heartworm status and additional parasite infections were confirmed by necropsy and adult helminth species verified morphologically or by PCR, and feces evaluated by centrifugal fecal flotation., Results: Intestinal parasites were confirmed in 140 of the dogs by necropsy, and 130 by fecal flotation. Acanthocheilonema reconditum microfilariae were confirmed in 22 dogs. Prevalence of heartworm infection confirmed by necropsy was 35.6% (58/163). In the 105 dogs without heartworms, specificity remained unchanged at 100% both before and after heat treatment despite confirmed infections with A. reconditum, Ancylostoma caninum, Ancylostoma brasiliense, Trichuris vulpis, Toxocara canis, Dipylidium caninum, Spirometra mansonoides, Macracanthorynchus ingens, Cystoisospora sp., Giardia sp., and Sarcocystis sp., Conclusions: These findings suggest that the use of heat treatment improves sensitivity of heartworm tests and is unlikely to cause false positive antigen results due to Acanthocheilonema reconditum, intestinal helminths, and protozoal parasites in dogs.

Background and Aims: The nature and outcomes of infection among patients with cirrhosis in safety-net hospitals are not well described. We aimed to characterize the rate of and risk factors for infection, both present on admission and nosocomial, in this unique population. We hypothesized that infections would be associated with adverse outcomes such as short-term mortality., Methods: We used descriptive statistics to characterize infections within a retrospective cohort characterized previously. We used multivariable logistic regression models to assess potential risk factors for infection and associations with key outcomes such as short-term mortality and length of stay., Results: The study cohort of 1112 patients included 33% women with a mean age of 56 ± 10 years. Infections were common (20%), with respiratory and urinary tract infections the most frequent. We did not observe a difference in the incidence of infection on admission based on patient demographic factors such as race/ethnicity or estimated household income. Infections on admission were associated with greater short-term mortality (12% vs 4% in-hospital and 14% vs 7% 30-day), longer length of stay (6 vs 3 days), intensive care unit admission (28% vs 18%), and acute-on-chronic liver failure (10% vs 2%) (p < 0.01 for all). Nosocomial infections were relatively uncommon (4%), but more frequent among patients admitted to the intensive care unit. Antibiotic resistance was common (38%), but not associated with negative outcomes., Conclusion: We did not identify demographic risk factors for infection, but did confirm its morbid effect among patients with cirrhosis in safety-net hospitals.

The American Heart Association (AHA) introduced Life's Simple 7 as a metric to define ideal cardiovascular health. We examined the association between cardiovascular health score (CHS) and prevalent nonalcoholic fatty liver disease (NAFLD) among Framingham Heart Study participants with varying genetic risk of NAFLD. Framingham Heart Study participants who underwent abdominal computed tomography scans were included (n = 2,773). We defined hepatic steatosis as the mean Hounsfield unit attenuation of the liver compared to a phantom control. We calculated CHS based on adherence to metrics from the AHA's Life's Simple 7 guidelines, including blood sugar, total cholesterol, blood pressure, body mass index (BMI), time spent on physical activity per week, and smoking status. We used multivariable-adjusted regression models to evaluate the association between CHS and hepatic steatosis, accounting for covariates and stratifying by NAFLD genetic risk. Overall, 12% of the sample achieved 0-1 goals and 25%, 27%, 21%, 13%, and 2.6% achieved 2, 3, 4, 5, or 6 goals, respectively. For each 1-unit increase in CHS, there was a decrease in the odds ratio (OR) of prevalent hepatic steatosis (OR, 0.54; 95% confidence interval, 0.49-0.59). Individually, BMI had the strongest association with NAFLD. Participants with high or intermediate genetic risk of NAFLD demonstrated higher relative decreases in hepatic steatosis with increased CHS compared to those at low genetic risk. Conclusion: Adhering to the AHA Life's Simple 7 metrics was associated with reduced odds of prevalent NAFLD, particularly for those at high genetic risk. Additional longitudinal studies are needed., (© 2020 The Authors. Hepatology Communications published by Wiley Periodicals LLC on behalf of the American Association for the Study of Liver Diseases.)

Background & Aims: Non-alcoholic fatty liver disease confers increased risk for cardiovascular disease, including heart failure (HF), for reasons that remain unclear. Possible pathways could involve an association of liver fat with cardiac structural or functional abnormalities even after accounting for body size., Methods: We analysed N = 2356 Framingham Heart Study participants (age 52 ± 12 years, 52% women) who underwent echocardiography and standardized computed tomography measures of liver fat., Results: In cross-sectional multivariable regression models adjusted for age, gender, cohort and cardiovascular risk factors, liver fat was positively associated with left ventricular (LV) mass (β = 1.45; 95% confidence interval (CI): 0.01, 2.88), LV wall thickness (β = 0.01; 95% CI: 0.00, 0.02), mass volume ratio (β = 0.02; 95% CI 0.01, 0.03), mitral peak velocity (E) (β = 0.83; 95% CI 0.31, 1.36) and LV filling pressure (E/e' ratio) (β = 0.16; 95% CI 0.09, 0.23); and inversely associated with global systolic longitudinal strain (β = 0.20, 95% CI 0.07, 0.33), diastolic annular velocity (e') (β = -0.12; 95% CI - 0.22, -0.03), and E/A ratio (β = -0.01; 95% CI - 0.02, -0.00). After additional adjustment for body mass index (BMI), statistical significance was attenuated for all associations except for that of greater liver fat with increased LV filling pressure, a possible precursor to HF (β = 0.11; 95% CI 0.03, 0.18)., Conclusion: Increased liver fat was associated with multiple subclinical cardiac dysfunction measures, with most of associations mediated by obesity. Interestingly, the association of liver fat and LV filling pressure was only partially mediated by BMI, suggesting a possible direct effect of liver fat on LV filling pressure. Further confirmatory studies are needed., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)