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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.
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BACKGROUND: Infections frequently complicate hospital admission among patients with cirrhosis and are associated with adverse outcomes. In specific settings, administration of prophylactic antibiotics has been shown to improve outcomes. In this pilot study, we aimed to assess the feasibility of a randomized study of whether prophylactic ceftriaxone (CTX), administered to hospitalized patients with advanced cirrhosis (Model for End-Stage Liver Disease-Sodium ≥ 18) without known infection, could reduce the incidence of infection. We also sought to determine whether we could identify patients most likely to benefit through the use of clinical and laboratory parameters. METHODS: Hospitalized patients with cirrhosis, with Model for End-Stage Liver Disease-Sodium ≥ 18 and no known infection after evaluation, were randomly assigned in a double-blinded fashion to receive either CTX 1 gr/day or placebo for up to 7 days. Subjects were monitored for incident infection and other outcomes of interest, including adverse reactions such as the development of C. difficile infection. Biomarkers of interest, including C-reactive protein and procalcitonin, were measured before initiation of treatment. RESULTS: Thirty subjects were enrolled and received CTX or placebo (15 subjects each) per protocol. There were no observed statistically significant differences between groups in incidence of infection, mortality, length of stay, or key laboratory parameters, including C-reactive protein and procalcitonin. Adverse events related to treatment were rare and clinically of minor significance. CONCLUSIONS: Overall, enrollment of subjects proved feasible, and results from this pilot study, while inadequate for confirmation of the potential efficacy of CTX, provide evidence of study feasibility for future, more definitive clinical trials.
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Clostridioides difficile , Enfermedad Hepática en Estado Terminal , Humanos , Proteína C-Reactiva , Ceftriaxona/efectos adversos , Cirrosis Hepática/complicaciones , Cirrosis Hepática/tratamiento farmacológico , Proyectos Piloto , Polipéptido alfa Relacionado con Calcitonina , Índice de Severidad de la Enfermedad , Sodio , Estudios de FactibilidadRESUMEN
Background Chronic disease, such as heart failure, influences cellular metabolism and shapes circulating metabolites. The relationships between key energy metabolites and chronic diseases in aging are not well understood. This study aims to determine the relationship between main components of energy metabolism with all-cause mortality and incident heart failure. Methods and Results We analyzed the association between plasma metabolite levels with all-cause mortality and incident heart failure among US older adults in the CHS (Cardiovascular Health Study). We followed 1758 participants without heart failure at baseline with hazard ratios (HRs) of analyte levels and metabolic profiles characterized by high levels of ketone bodies for all-cause mortality and incident heart failure. Multivariable Cox analyses revealed a dose-response relationship of 50% increase in all-cause mortality between lowest and highest quintiles of ketone body concentrations (HR, 1.5 [95% CI, 1.0-1.9]; P=0.007). Ketone body levels remained associated with incident heart failure after adjusting for cardiovascular disease confounders (HR, 1.2 [95% CI, 1.0-1.3]; P=0.02). Using K-means cluster analysis, we identified a cluster with higher levels of ketone bodies, citrate, interleukin-6, and B-type natriuretic peptide but lower levels of pyruvate, body mass index, and estimated glomerular filtration rate. The cluster with elevated ketone body levels was associated with higher all-cause mortality (HR, 1.7 [95% CI, 1.1-2.7]; P=0.01). Conclusions Higher concentrations of ketone bodies predict incident heart failure and all-cause mortality in an older US population, independent of metabolic and cardiovascular confounders. This association suggests a potentially important relationship between ketone body metabolism and aging.
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Enfermedades Cardiovasculares , Insuficiencia Cardíaca , Humanos , Anciano , Incidencia , Insuficiencia Cardíaca/diagnóstico , Insuficiencia Cardíaca/epidemiología , Envejecimiento , Cuerpos CetónicosRESUMEN
The molecular underpinnings of organ dysfunction in acute COVID-19 and its potential long-term sequelae are under intense investigation. To shed light on these in the context of liver function, we performed single-nucleus RNA-seq and spatial transcriptomic profiling of livers from 17 COVID-19 decedents. We identified hepatocytes positive for SARS-CoV-2 RNA with an expression phenotype resembling infected lung epithelial cells. Integrated analysis and comparisons with healthy controls revealed extensive changes in the cellular composition and expression states in COVID-19 liver, reflecting hepatocellular injury, ductular reaction, pathologic vascular expansion, and fibrogenesis. We also observed Kupffer cell proliferation and erythrocyte progenitors for the first time in a human liver single-cell atlas, resembling similar responses in liver injury in mice and in sepsis, respectively. Despite the absence of a clinical acute liver injury phenotype, endothelial cell composition was dramatically impacted in COVID-19, concomitantly with extensive alterations and profibrogenic activation of reactive cholangiocytes and mesenchymal cells. Our atlas provides novel insights into liver physiology and pathology in COVID-19 and forms a foundational resource for its investigation and understanding.
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BACKGROUND & AIM: Liver fibrosis is associated with poor patient-reported outcomes (PROs), but the impact of steatosis is unknown. We aimed to evaluate the impact of steatosis on PROs independent of liver fibrosis. METHODS: We evaluated the impact of steatosis, measured by Controlled-Attenuation Parameter (CAP) on transient elastography, and PROs using the 2017-2018 National Health and Nutrition Examination Survey (NHANES) database. We used univariate and multivariate logistic and ordinal regression to evaluate categorical CAP score with PROs measuring physical disability, general health and depression. RESULTS: Of 4,509 participants included, 38% had severe steatosis (> 280 dB/m). Those with severe steatosis were older and more likely to be male (56% vs. 43% and 51%). On univariate analysis, severe steatosis was associated with more difficulty walking (P = 0.01), dressing (P = 0.005), lifting objects (P = 0.02), bending (P < 0.001), and moving large objects (P = 0.0006). After multivariate adjustment, severe steatosis remained associated with difficulty lifting objects (odds ratio [OR]: 1.7, 95% confidence interval [CI]: 1.2-2.4, P = 0.01) and difficulty bending (OR: 1.8, 95% CI: 1.2-2.7, P = 0.006). Severe steatosis increased risk of having any of the disabilities (OR: 1.7, 95% CI: 1.2-2.4, P = 0.008) and had higher ordinal disability index (OR: 1.6, 95% CI: 1.2-2.2, P = 0.007). Lastly, severe steatosis was also associated with worse self-perceived health status (OR: 1.5, 95% CI: 1.2-1.9, P = 0.002), while general health compared to one year ago and depression trended toward significance. CONCLUSION: Patients with severe steatosis are at increased risk of physical disability and have worse self-perceived health status independent of liver fibrosis.
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Diagnóstico por Imagen de Elasticidad , Hígado Graso , Enfermedad del Hígado Graso no Alcohólico , Hígado Graso/patología , Femenino , Humanos , Hígado/patología , Cirrosis Hepática/patología , Masculino , Enfermedad del Hígado Graso no Alcohólico/patología , Encuestas Nutricionales , Calidad de VidaRESUMEN
BACKGROUND & AIMS: Coffee is associated with a reduced risk of liver disease. This association is limited by important sources of confounding such as recall bias, healthy user bias, and indirect measures of liver outcomes or health. We aimed to examine the impact of coffee consumption with liver fibrosis and steatosis in a nationally representative sample. METHODS: We evaluated 4510 subjects 20 years and older from the 2017 to 2018 National Health and Nutrition Examination Survey study who underwent both transient elastography and two 24-hour dietary recall examinations. We tested the associations between liver stiffness measurements (LSM) of 9.5 kpa or greater or controlled attenuation parameter (CAP) and coffee consumption. We used decaffeinated coffee and tea consumption as controls. As a sensitivity analysis, we included all drinks in 1 model, examined the impact of caffeine consumption, and adjusted for the Healthy Eating Index-2015 and sugar-sweetened beverage consumption as separate models. RESULTS: The study sample described was aged 48 ± 0.6 years, 73% were overweight or obese, 10.6% had diabetes, 47.5% reported participation in vigorous physical activity, and 23% drank 2 or more alcoholic drinks per day. After multivariate adjustment, there was no association between coffee and controls with CAP. Subjects who drank more than 3 cups of coffee, but not other drinks, had a 0.9 lower kPa (95% CI, -1.6 to -0.1; P = .03). More than 3 cups of coffee were protective for LSM of 9.5 kpa or higher (odds ratio, 0.4; 95% CI, 0.2-1.0; P = .05). Accounting for all beverages in the same model, only consuming more than 3 cups of coffee remained independently associated with LSM (odds ratio, 0.5; 95% CI, 0.2-0.9; P = .03). Caffeine was not associated significantly with LSM at any dose. Finally, adjusting for sugar-sweetened beverage consumption and Healthy Eating Index-2015, coffee consumption remained associated with a lower LSM. The protective nature of coffee consumption therefore is not attributable to caffeine and persists in participants regardless of their diet quality. CONCLUSIONS: Coffee is associated with lower liver stiffness, but not steatosis, as measured by CAP among US adults.
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Café , Hígado Graso , Adulto , Bebidas , Cafeína , Humanos , Encuestas Nutricionales , TéRESUMEN
Cirrhosis, a rising cause of death in the United States, has an extended preclinical phase characterized by progressive liver fibrosis. Despite the developments in noninvasive fibrosis measurement, there is no recommended screening, in part due to an incomplete understanding of the disease epidemiology on a national scale. Herein, we aim to define the prevalence of liver fibrosis and compare strategies to identify the at-risk population. We analyzed 4,510 US adults with complete liver stiffness measurement (LSM) by vibration-controlled transient elastography (VCTE) in the 2017-2018 National Health and Nutrition Examination Survey to estimate the disease burden of increased liver stiffness. An estimated 11.6 million (95% confidence interval [C.I.], 8.1-15.0 million) US adults had LSM ≥9.5 kPa, indicating advanced fibrosis and representing 1 in every 18 adults. Among them, 7.1 million (95% CI, 5.0-9.1 million) had LSM ≥12.5 kPa, which is concerning for cirrhosis. LSM ≥9.5 kPa is associated with male sex (S), history of other liver diseases (O), diabetes (D), advanced age (A), and an elevated BMI (B). A simple SODA-2B score had a sensitivity of 96.4% in identifying individuals at risk for advanced cirrhosis (LSM ≥9.5 kPa) and a negative predictive value of 99.3% in stratifying more than half of the adult population. When the liver function test (LFT) is available, the inclusion of abnormal LFT and elevated fibrosis-4 index can further increase screening efficiency. Conclusion: Elevated liver stiffness is prevalent among US adults. A SODA-2B score can risk stratify adults for VCTE-based fibrosis screening.
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Diagnóstico por Imagen de Elasticidad , Adulto , Humanos , Cirrosis Hepática/diagnóstico , Masculino , Encuestas Nutricionales , PrevalenciaRESUMEN
BACKGROUND AND AIMS: Lipoprotein Z (LP-Z) is an abnormal free cholesterol (FC)-enriched LDL-like particle discovered from patients with cholestatic liver disease. This study aims to define the diagnostic value of LP-Z in alcohol-associated hepatitis (AH) and interrogate the biology behind its formation. APPROACH AND RESULTS: We measured serum levels of LP-Z using nuclear magnetic resonance spectroscopy, a well-established clinical assay. Serum levels of LP-Z were significantly elevated in four AH cohorts compared with control groups, including heavy drinkers and patients with cirrhosis. We defined a Z-index, calculated by the ratio of LP-Z to total apolipoprotein B-containing lipoproteins, representing the degree of deviation from normal VLDL metabolism. A high Z-index was associated with 90-day mortality independent from the Model for End-Stage Liver Disease (MELD) and provided added prognosticative value. Both a Z-index ≤ 0.6 and a decline of Z-index by ≥0.1 in 2 weeks predicted 90-day survival. RNA-sequencing analyses of liver tissues demonstrated an inverse association in the expression of enzymes responsible for the extrahepatic conversion of VLDL to LDL and AH disease severity, which was further confirmed by the measurement of serum enzyme activity. To evaluate whether the FC in LP-Z could contribute to the pathogenesis of AH, we found significantly altered FC levels in liver explant of patients with AH. Furthermore, FC in reconstituted LP-Z particles caused direct toxicity to human hepatocytes in a concentration-dependent manner, supporting a pathogenic role of FC in LP-Z. CONCLUSIONS: Impaired lipoprotein metabolism in AH leads to the accumulation of LP-Z in the circulation, which is hepatotoxic from excessive FC. A Z-index ≤ 0.6 predicts 90-day survival independent from conventional biomarkers for disease prognostication.
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Enfermedad Hepática en Estado Terminal , Hepatitis Alcohólica , Apolipoproteínas B , Colesterol , Humanos , Lipoproteína(a) , Lipoproteínas , Índice de Severidad de la EnfermedadRESUMEN
Despite being widely recognized as a common cause of fatty liver, the exact impact of alcohol consumption on hepatic steatosis in the general population is elusive. The recent National Health and Nutrition Examination Survey (NHANES) allowed us to examine this relationship among US adults. Herein, we extracted data on detailed alcohol consumption and controlled attenuation parameter (CAP) by FibroScan from 4509 participants in NHANES 2017-2018. Compared to metabolic risk factors such as diabetes and obesity, the association between alcohol consumption and CAP was less significant. In multivariable analysis, only those drinking 5-7 times per week showed significant increases in CAP scores. Although both frequency and quantity of drinking were positively associated with CAP score, only frequency remained significant after adjustment for quantity and binge drinking. These epidemiological observations suggested that the impact of alcohol on hepatic steatosis was much smaller than metabolic factors and dependent upon the frequency of drinking.
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Diagnóstico por Imagen de Elasticidad , Hígado Graso , Enfermedad del Hígado Graso no Alcohólico , Adulto , Consumo de Bebidas Alcohólicas/efectos adversos , Consumo de Bebidas Alcohólicas/epidemiología , Hígado Graso/diagnóstico por imagen , Hígado Graso/epidemiología , Hígado Graso/etiología , Humanos , Encuestas Nutricionales , Obesidad/complicaciones , Obesidad/epidemiología , Estados Unidos/epidemiologíaRESUMEN
COVID-19, which is caused by SARS-CoV-2, can result in acute respiratory distress syndrome and multiple organ failure1-4, but little is known about its pathophysiology. Here we generated single-cell atlases of 24 lung, 16 kidney, 16 liver and 19 heart autopsy tissue samples and spatial atlases of 14 lung samples from donors who died of COVID-19. Integrated computational analysis uncovered substantial remodelling in the lung epithelial, immune and stromal compartments, with evidence of multiple paths of failed tissue regeneration, including defective alveolar type 2 differentiation and expansion of fibroblasts and putative TP63+ intrapulmonary basal-like progenitor cells. Viral RNAs were enriched in mononuclear phagocytic and endothelial lung cells, which induced specific host programs. Spatial analysis in lung distinguished inflammatory host responses in lung regions with and without viral RNA. Analysis of the other tissue atlases showed transcriptional alterations in multiple cell types in heart tissue from donors with COVID-19, and mapped cell types and genes implicated with disease severity based on COVID-19 genome-wide association studies. Our foundational dataset elucidates the biological effect of severe SARS-CoV-2 infection across the body, a key step towards new treatments.
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COVID-19/patología , COVID-19/virología , Riñón/patología , Hígado/patología , Pulmón/patología , Miocardio/patología , SARS-CoV-2/patogenicidad , Adulto , Anciano , Anciano de 80 o más Años , Atlas como Asunto , Autopsia , Bancos de Muestras Biológicas , COVID-19/genética , COVID-19/inmunología , Células Endoteliales , Células Epiteliales/patología , Células Epiteliales/virología , Femenino , Fibroblastos , Estudio de Asociación del Genoma Completo , Corazón/virología , Humanos , Inflamación/patología , Inflamación/virología , Riñón/virología , Hígado/virología , Pulmón/virología , Masculino , Persona de Mediana Edad , Especificidad de Órganos , Fagocitos , Alveolos Pulmonares/patología , Alveolos Pulmonares/virología , ARN Viral/análisis , Regeneración , SARS-CoV-2/inmunología , Análisis de la Célula Individual , Carga ViralRESUMEN
The SARS-CoV-2 pandemic has caused over 1 million deaths globally, mostly due to acute lung injury and acute respiratory distress syndrome, or direct complications resulting in multiple-organ failures. Little is known about the host tissue immune and cellular responses associated with COVID-19 infection, symptoms, and lethality. To address this, we collected tissues from 11 organs during the clinical autopsy of 17 individuals who succumbed to COVID-19, resulting in a tissue bank of approximately 420 specimens. We generated comprehensive cellular maps capturing COVID-19 biology related to patients' demise through single-cell and single-nucleus RNA-Seq of lung, kidney, liver and heart tissues, and further contextualized our findings through spatial RNA profiling of distinct lung regions. We developed a computational framework that incorporates removal of ambient RNA and automated cell type annotation to facilitate comparison with other healthy and diseased tissue atlases. In the lung, we uncovered significantly altered transcriptional programs within the epithelial, immune, and stromal compartments and cell intrinsic changes in multiple cell types relative to lung tissue from healthy controls. We observed evidence of: alveolar type 2 (AT2) differentiation replacing depleted alveolar type 1 (AT1) lung epithelial cells, as previously seen in fibrosis; a concomitant increase in myofibroblasts reflective of defective tissue repair; and, putative TP63+ intrapulmonary basal-like progenitor (IPBLP) cells, similar to cells identified in H1N1 influenza, that may serve as an emergency cellular reserve for severely damaged alveoli. Together, these findings suggest the activation and failure of multiple avenues for regeneration of the epithelium in these terminal lungs. SARS-CoV-2 RNA reads were enriched in lung mononuclear phagocytic cells and endothelial cells, and these cells expressed distinct host response transcriptional programs. We corroborated the compositional and transcriptional changes in lung tissue through spatial analysis of RNA profiles in situ and distinguished unique tissue host responses between regions with and without viral RNA, and in COVID-19 donor tissues relative to healthy lung. Finally, we analyzed genetic regions implicated in COVID-19 GWAS with transcriptomic data to implicate specific cell types and genes associated with disease severity. Overall, our COVID-19 cell atlas is a foundational dataset to better understand the biological impact of SARS-CoV-2 infection across the human body and empowers the identification of new therapeutic interventions and prevention strategies.
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Background and study aims Colonoscopy is an effective tool to prevent colorectal cancer. Social media has emerged as a source of medical information for patients.YouTube (a video sharing website) is the most popular video informative source. Therefore, we aimed to assess the educational quality of colonoscopy videos available on YouTube. Methods We performed a YouTube search using the keyword "colonoscopy" yielded 429 videos, of which 255 met the inclusion criteria. Colonoscopy Data Quality Score (C-DQS) was created to rate the quality of the videos (-10 to +40 points) based on a colonoscopy education video available on the Ameican Society of Gastrointestinal Endoscopy (ASGE) website. Each video was scored by six blinded reviewers independently using C-DQS.âThe Global Quality Score (GQS) was used for score validation. The intraclass correlation coefficient (ICC) was used to assess the similarity of the scores among reviewers. Results Professional societies had the highest number of videos (44.3â%). Videos from professional societies (6.94) and media (6.87) had significantly higher mean C-DQS compared to those from alternative medicine providers (1.19), companies (1.16), and patients (2.60) ( P â<â0.05). Mean C-DQS score of videos from healthcare providers (4.40) was not statistically different than other sources. There was a high degree of agreement among reviewers for the videos from all sources (ICCâ=â0.934; P â<â0.001). Discussion YouTube videos are a poor source of information on colonoscopy. Professional societies and media are better sources of quality information for patient education on colonoscopy. The medical community may need to engage actively in enriching the quality of educational material available on YouTube.
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Diabetic kidney disease (DKD) is the major contributor to the mortality and the financial burden of diabetes, accounting for approximately 50% of the cases of end-stage renal disease (ESRD) in the developed world. Several studies have already demonstrated that achieving blood pressure targets in DKD with agents blocking the renin-angiotensin system confer superior renoprotection when compared to other agents. However, the effects on renal outcomes of antihyperglycaemic agents in these patients have not been reported or studied broadly until recent years. The intent of this article is to review the available data on safety, efficacy, impact on renal outcomes and pathophysiology implications of the most utilized antihyperglycaemic agents in DKD/ESRD.