Risk of severe illness of COVID‐19 patients with NAFLD and increased NAFLD fibrosis scores

BackgroundThere is still little knowledge about the association of liver fibrosis with the clinical outcomes of COVID‐19 patients with non‐alcoholic fatty liver disease (NAFLD). The aim of the study was to determine the association of NAFLD fibrosis score (NFS)–determined liver fibrosis with clinical outcomes of COVID‐19 patients with NAFLD.MethodsThe NAFLD was diagnosed by the Hepatic Steatosis Index (HSI) in the absence of other causes of chronic liver diseases. NFS was used to evaluate the severity of liver fibrosis.ResultsA total of 86 COVID‐19 patients with NAFLD were included. The median age was 43.5 years, and 58.1% of patients were male. Thirty‐eight (44.2%) patients had advanced liver fibrosis according to the NFS. Multivariate analysis indicated that concurrent diabetes (odds ratio [OR] 8.264, 95% confidence interval [CI] 1.202–56.830, p = 0.032) and advanced liver fibrosis (OR 11.057, 95% CI 1.193–102.439, p = 0.034) were independent risk factors of severe illness in COVID‐19 patients with NAFLD.ConclusionNAFLD patients with NFS‐determined advanced liver fibrosis are at higher risk of severe COVID‐19.     

The association between non‐alcoholic fatty liver disease and serum ferritin levels in American adults

BackgroundElevated serum ferritin levels (SFLs) was previously reported to be related with hepatic histologic severity and advanced liver fibrosis among non‐alcoholic fatty liver disease (NAFLD) patients. However, whether NAFLD influences SFLs remains uncertain and needs more clinical evidences. This study explored the differences of SFLs in US adults with or without NAFLD.MethodsWe conducted a cross‐sectional study of 3689 participants aged 18–80 years using the National Health and Nutrition Examination Survey (NHANES) 2017–2018 cycle. NAFLD status was confirmed based on controlled attenuation parameter (CAP) values ≥274 dB/m through vibration controlled and transient elastography (VCTE). We performed weighted multivariable logistic regression models to evaluate the associations between NAFLD and SFLs in different age and gender.ResultsThere was a positive association between NAFLD and SFLs in all three models (model 1:β = 23.07, 95% CI: 10.32, 35.81; model 2:β = 23.68, 95% CI: 10.86, 36.50; model 3:β = 13.86, 95% CI: 0.29, 27.43). After adjusting for the covariates, this positive association persisted in females (β = 16.22, 95% CI: 2.81, 29.62). Further, relationships between NAFLD and SFLs were significantly different in various age groups. In the subgroup stratified by gender, their associations further differed. In males, the positive association was more prominent in 50–64 age group (β = 70.89, 95% CI: 25.14, 116.64). In females, this positive association was more prominent in 18–34 age group (β = 20.72, 95% CI: 7.45, 33.99). However, no correlations between severe steatosis, significant fibrosis, advanced fibrosis, cirrhosis, and SFLs in adults with NAFLD were found.ConclusionThis study indicated that US adults suffered with NAFLD had significantly higher SFLs compared with their counterparts in non‐NAFLD group. Moreover, the associations between NAFLD and SFLs further differed by age and gender.     

Relationship between non-alcoholic fatty liver disease and cardiac arrhythmia: a systematic review and meta-analysis

ObjectiveWe performed a meta-analysis to create a quantitative estimate of the association between non-alcoholic fatty liver disease (NAFLD) and the risk of cardiac arrhythmia (including atrial fibrillation (AF), prolonged QT interval, premature atrial/ventricular contraction [PAC/PVC] and heart block).MethodsA literature review was conducted using PubMed, Embase, Web of Science and the Cochrane Library database to identify observational studies of the link between NAFLD and cardiac arrhythmia. Effect sizes were expressed as odds ratios (ORs) or hazard ratios (HRs) with 95% confidence intervals (CIs). The method of analysis of AF was also analysed separately, according to the effect estimate (OR or HR).ResultsNineteen studies of 7,012,960 individuals were included. NAFLD was independently associated with higher risks of AF (OR 1.71, 95% CI: 1.14–2.57; HR 1.12, 95% CI: 1.11–1.13), prolonged QT interval (OR 2.86, 95% CI: 1.64–4.99), PAC/PVC (OR 2.53, 95% CI: 1.70–3.78) and heart block (OR 2.65, 95% CI: 1.88–3.72). The heterogeneity of the data with respect to AF and prolonged QT was moderate on sensitivity analysis.ConclusionsWe found a significantly higher risk of cardiac arrhythmia in patients with NAFLD, but the observational design of the studies does not permit conclusions regarding causality.     

Current pet ownership modifies the adverse association between long‐term ambient air pollution exposure and childhood asthma

BackgroundRecent studies suggest that household endotoxin and allergens can modify the impact of air pollutants on development of asthma; however, epidemiological evidence is limited and conflicting.ObjectivesTo investigate whether pet ownership modified the association between ambient air pollution and asthma in children.MethodsWe conducted a population‐based cross‐sectional study, the Seven Northeast Cities Study in China and recruited a total of 59,754 children from 94 schools during 2012–2013. Long‐term air pollutant concentrations, including airborne particulate matter with a diameter of 1 μm or less (PM₁), PM_2.5, PM₁₀, and nitrogen dioxide (NO₂) from 2009 to 2012 were estimated using a random forest model. We collected information of respiratory health in children using the Epidemiologic Standardization Project Questionnaire of the American Thoracic Society (ATS‐DLD‐78‐A). Regression models were used to evaluate associations between pet ownership and air pollution on asthma after adjusting for potential covariates.ResultsExposure to increasing levels of air pollutants was associated with higher prevalence of asthma, but associations were significantly attenuated in children who owned pets. For example, compared to children without pets, those who owned pets did not have an increased risk of symptoms of asthma (odds ratio, 1.01, 95% confidence interval: 0.78, 1.30), wheeze (0.96, 95% confidence interval [CI]: 0.76, 1.21), and cough (1.01, 95% CI: 0.87, 1.18) for each 10 µg/m³ increase in PM₁ (P _‐int < 0.05). Similar trends were observed for other air pollutants. Dog and bird ownership decreased the associations of asthma and cough with air pollutant exposure. The main findings were consistent with a series of sensitivity analyses.ConclusionCurrent pet ownership may reduce the adverse impact of long‐term air pollution on childhood asthma. Longitudinal studies are needed to confirm this finding which could have important implications for public health.     

Predictive value of lymphocyte‐to‐monocyte ratio in critically Ill patients with atrial fibrillation: A propensity score matching analysis

BackgroundInflammation plays a key role in the initiation and progression of atrial fibrillation (AF). Lymphocyte‐to‐monocyte ratio (LMR) has been proved to be a reliable predictor of many inflammation‐associated diseases, but little data are available on the relationship between LMR and AF. We aimed to evaluate the predictive value of LMR in predicting all‐cause mortality among AF patients.MethodsData of patients diagnosed with AF were retrieved from the Medical Information Mart for Intensive Care‐III (MIMIC‐III) database. X‐tile analysis was used to calculate the optimal cutoff value for LMR. The Cox regression model was used to assess the association of LMR and 28‐day, 90‐day, and 1‐year mortality. Additionally, a propensity score matching (PSM) method was performed to minimize the impact of potential confounders.ResultsA total of 3567 patients hospitalized with AF were enrolled in this study. The X‐tile software indicated that the optimal cutoff value of LMR was 2.67. A total of 1127 pairs were generated, and all the covariates were well balanced after PSM. The Cox proportional‐hazards model showed that patients with the low LMR (≤2.67) had a higher 1‐year all‐cause mortality than those with the high LMR (>2.67) in the study cohort before PSM (HR = 1.640, 95% CI: 1.437–1.872, p < 0.001) and after PSM (HR = 1.279, 95% CI: 1.094–1.495, p = 0.002). The multivariable Cox regression analysis for 28‐day and 90‐day mortality yielded similar results.ConclusionsThe lower LMR (≤2.67) was associated with a higher risk of 28‐day, 90‐day, and 1‐year all‐cause mortality, which might serve as an independent predictor in AF patients.     

Combined fibrinogen‐to‐pre‐albumin ratio and carbohydrate antigen 19–9 score is a promising metric to predict progression of metastatic colorectal mucinous adenocarcinoma

BackgroundChronic inflammation is a hallmark of colorectal mucinous adenocarcinoma (CMA). Albumin‐to‐fibrinogen ratio (AFR) and fibrinogen‐to‐pre‐albumin ratio (FPR) were independent prognostic factors for many kinds of solid malignancies. However, the association between the inflammatory scores and progression of metastatic CMA remains unknown.MethodsPeripheral blood neutrophil count and circulating fibrinogen, albumin, and pre‐albumin levels were detected, and neutrophil‐to‐albumin ratio (NAR), neutrophil‐to‐pre‐albumin ratio(NPAR), AFR, and FPR were calculated in 42 metastatic MCA patients. Kaplan‐Meier curve, Cox regression, time‐dependent receiver operating characteristic curve (tdROC) were selected to investigate the prognostic utility of them in the patients.ResultsMetastatic CMA patients commonly occurred in middle‐younger patients (80.95%). NPAR (adjusted hazard ratio (HR)=2.405, 95% confidence interval (CI)=1.195–4.842) and FPR (p _log‐rank=0.007, adjusted HR=2.364, 95% CI=1.203–4.645) were significantly associated with poor progression‐free survival in these patients. The prognostic prediction area under tdROC (AUROC) of FPR was significantly higher than that of NPAR(0.703 versus 0.537). Moreover, the patients with a high CA19‐9‐FPR score showed worse outcomes than those with the low score (p _log‐rank<0.001, adjusted HR=7.273, 95% CI=2.721–19.435 for the score 1 versus 0). The prediction AUROC, sensitivity, and specificity of the score were 0.892 (0.788–0.996), 76.32%, and 100.00%, respectively, and its predicted efficacy was better than that of the single biomarkers.ConclusionThe combined CA19‐9‐FPR score is an economical, simple, effective, and independent prognostic factor for metastatic MCA.     

In‐hospital mortality in SARS‐CoV‐2 stratified by gamma‐glutamyl transferase levels

BackgroundThis study investigates in‐hospital mortality amongst patients with severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) and its relation to serum levels of gamma‐glutamyl transferase (GGT).MethodsPatients were stratified according to serum levels of gamma‐glutamyl transferase (GGT) (GGT<50 IU/L or GGT≥50 IU/L).ResultsA total of 802 participants were considered, amongst whom 486 had GGT<50 IU/L and a mean age of 48.1 (16.5) years, whilst 316 had GGT≥50 IU/L and a mean age of 53.8 (14.7) years. The chief sources of SARS‐CoV‐2 transmission were contact (366, 45.7%) and community (320, 40%). Most patients with GGT≥50 IU/L had either pneumonia (247, 78.2%) or acute respiratory distress syndrome (ARDS) (85, 26.9%), whilst those with GGT<50 IU/L had hypertension (141, 29%) or diabetes mellitus (DM) (147, 30.2%). Mortality was higher amongst patients with GGT≥50 IU/L (54, 17.1%) than amongst those with GGT<50 IU/L (29, 5.9%). More patients with GGT≥50 required high (83, 27.6%) or low (104, 34.6%) levels of oxygen, whereas most of those with GGT<50 had no requirement of oxygen (306, 71.2%). Multivariable logistic regression analysis indicated that GGT≥50 IU/L (odds ratio [OR]: 2.02, 95% confidence interval [CI]: 1.20–3.45, p=0.009), age (OR: 1.05, 95% CI: 1.03–1.07, p<0.001), hypertension (OR: 2.06, 95% CI: 1.19–3.63, p=0.011), methylprednisolone (OR: 2.96, 95% CI: 1.74–5.01, p<0.001) and fever (OR: 2.03, 95% CI: 1.15–3.68, p=0.016) were significant predictors of all‐cause cumulative mortality. A Cox proportional hazards regression model (B = −0.68, SE =0.24, HR =0.51, p = 0.004) showed that patients with GGT<50 IU/L had a 0.51‐times lower risk of all‐cause cumulative mortality than patients with GGT≥50 IU/L.ConclusionHigher levels of serum GGT were found to be an independent predictor of in‐hospital mortality.     

Malnutrition on admission increases the in‐hospital mortality and length of stay in elder adults with acute ischemic stroke

PurposeMalnutrition, as determined by the Controlling Nutritional Status (CONUT), has an effect on the 3‐month and long‐term prognosis of stroke patients. The association between malnutrition and in‐hospital mortality has not been well established. We aimed to investigate the relationship between the CONUT score on admission and in‐hospital mortality and length of stay (LOS) in elderly patients with acute ischemic stroke (AIS).MethodsThis study analyzed controls and patients with AIS. Malnutrition was determined using the CONUT score. A CONUT score of 5–12 was defined as undernutrition status. Based on the CONUT scores, the patients were divided into the low CONUT (0–4) and high CONUT (5–12) groups.ResultsIn total, 1079 participants were recruited, comprising 288 controls and 791 AIS patients. Among the 791 patients, 64 (8.1%) had malnutrition and 63 (7.9%) had an in‐hospital death. Compared to the controls, the AIS patients presented higher CONUT scores, higher proportion of in‐hospital mortality (8.0%), and longer length of stay. Malnutrition was independently associated with in‐hospital mortality in the AIS patients (adjusted odds ratio: 3.77, 95% confidence interval [CI]: 1.55–9.15; p = 0.003). The general linear models showed an association between the CONUT score and LOS (β = 0.574, 95% CI: 0.208–0.934; p = 0.002). Furthermore, the effect of the interaction between infection and nutrition status on in‐hospital mortality showed borderline statistical significance (p = 0.06).ConclusionsMalnutrition estimated by the CONUT score on admission can be a predictor of in‐hospital mortality and increased LOS in elderly AIS patients.     

Incidence of anaphylaxis and accidental peanut exposure: A systematic review

BackgroundPeanut allergy (PA), a common food allergy, is increasing in prevalence and is associated with high rates of anaphylaxis. Prevalence of food‐related anaphylaxis is higher in children and adolescents than in adults, and the pediatric incidence is increasing. We conducted a systematic literature review and meta‐analysis to determine the incidence of peanut‐induced anaphylaxis in children and/or adolescents with PA.MethodsLiterature searches were conducted using the PubMed database and through supplemental methods. Eligible articles for inclusion were peer‐reviewed studies published in English that reported the incidence of anaphylaxis in pediatric PA using the 2006 National Institute of Allergy and Infectious Disease/Food Allergy and Anaphylaxis Network criteria, sample size, and follow‐up duration. Incidence rates were calculated as person‐years at risk or a crude incidence rate was calculated. Meta‐analyses of pooled data were conducted using the I ² statistic as the measure of heterogeneity.ResultsA total of 830 citations were screened; 8 met the study inclusion criteria and were selected for review. Pooled meta‐analysis estimates of the incidence of (1) anaphylaxis among children/adolescents with food allergies, (2) anaphylaxis among children/adolescents with PA, and (3) accidental exposure to peanuts among children/adolescents with PA were 3.72 cases per 100 person‐years (95% confidence interval [CI] = 2.35, 5.10), 2.74 cases per 100 person‐years (95% CI = 1.42, 4.05), and 12.28 cases per 100 person‐years (95% CI = 11.51, 13.05), respectively.ConclusionsThe risks of anaphylaxis among children with food allergies and those with PA contribute to the serious overall burden of PA and food allergy for children and their families.     

Risk factors for prolonged virus shedding of respiratory tract and fecal in adults with severe acute respiratory syndrome coronavirus‐2 infection

BackgroundThe dynamic alteration and comparative study of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) RNA shedding pattern during treatment are limited. This study explores the potential risk factors influencing prolonged viral shedding in COVID‐19.MethodsA total of 126 COVID‐19 patients were enrolled in this retrospective longitudinal study. A multivariate logistic regression analysis was carried out to estimate the potential risk factors.Results38.1% (48/126) cases presented prolonged respiratory tract viral shedding, and 30 (23.8%) cases presented prolonged rectal swab viral shedding. Obesity (OR, 3.31; 95% CI, 1.08–10.09), positive rectal swab (OR, 3.43; 95% CI, 1.53–7.7), treatment by lopinavir/ritonavir with chloroquine phosphate (OR, 2.5; 95% CI, 1.04–6.03), the interval from onset to antiviral treatment more than 7 days (OR, 2.26; 95% CI, 1.04–4.93), lower CD4+ T cell (OR, 0.92; 95% CI, 0.86–0.99) and higher NK cells (OR, 1.11; 95% CI, 1.02–1.20) were significantly associated with prolonged respiratory tract viral shedding. CD3−CD56+ NK cells (OR, 0.87; 95% CI, 0.76–0.99) were related with prolonged fecal shedding.ConclusionsObesity, delayed antiviral treatment, and positive SARS‐CoV‐2 for stool were independent risk factors for prolonged SARS‐CoV‐2 RNA shedding of the respiratory tract. A combination of LPV/r and abidol as the initial antiviral regimen was effective in shortening the duration of viral shedding compared with LPV/r combined with chloroquine phosphate. CD4+ T cell and NK cells were significantly associated with prolonged viral shedding, and further studies are to be warranted to determine the mechanism of immunomodulatory response in virus clearance.     

Association between the liver fat score (LFS) and cardiovascular diseases in the national health and nutrition examination survey 1999–2016

BackgroundThe liver fat score (LFS) has been proposed to be a simple non-invasive marker of non-alcoholic fatty liver disease (NAFLD), which is highly prevalent in the general population. We tested its association with cardiovascular diseases (CVDs) and prognosis.Methods17,244 adult participants from the National Health and Nutrition Examination Survey 1999–2016 were included. LFS is calculated from variables including serum aspartate transaminase/alanine transaminase (AST/ALT) ratio, fasting serum aspartate transaminase (AST) level, fasting serum insulin level, presence of metabolic syndrome and diabetes mellitus. In cross-sectional analysis, logistic regression was used to examine the association of the LFS with coronary heart disease (CHD), myocardial infarction (MI), congestive heart failure (CHF), stroke and angina pectoris. Mortality during follow-up was analysed using Cox proportional hazard regression.ResultsLFS was associated with CHD (adjusted odds ratio [OR]: 1.09 per standard deviation [SD], 95% confidence interval [95% CI]: 1.03–1.15) (p = .003), CHF (1.11, 1.04–1.18) (p = .003) and angina pectoris (1.08, 1.02–1.13) (p = .005). LFS was not associated with MI or stroke, but was associated with increased all-cause and cardiovascular mortality with hazard ratios (HRs) of 1.10 (95% CI: 1.07–1.13) (p < .001) and 1.12 (95% CI: 1.06–1.17) (p < .001), respectively.ConclusionsNAFLD is usually asymptomatic, but this large study of a large general population shows that LFS is associated with CHD, CHF, angina pectoris, cardiovascular and all-cause mortality. Determining the LFS is worthwhile, as it identifies people with NAFLD, who may also be at increased cardiovascular risk.

Key Messages

• Liver fat score (LFS), a non-invasive marker of non-alcoholic fatty liver disease (NAFLD), is associated with coronary heart disease (CHD), congestive heart failure (CHF) and angina.
• LFS is also associated with increased cardiovascular and all-cause mortality.
• Determining the LFS is worthwhile as it identifies people with NAFLD as well as increased cardiovascular risk.

     

High NAFLD fibrosis score in non-alcoholic fatty liver disease as a predictor of carotid plaque development: a retrospective cohort study based on regular health check-up data in China

PurposesThere is increasing concern regarding cardiovascular risk in non-alcoholic fatty liver disease (NAFLD) patients with liver fibrosis. This study aims: (1) to assess the association between NAFLD and liver fibrosis status and the development of carotid plaque (CP), and (2) to identify CP risk factors among general population with different baseline NAFLD and liver fibrosis status.MethodsThis retrospective cohort study included 14,288 adult participants who went for regular health check-ups between 2014 and 2019, in one hospital in Zhejiang, China. NAFLD was diagnosed by abdominal ultrasound and the NAFLD fibrosis score (NFS) was calculated to reflect the extent of liver fibrosis. Cox proportional hazards analyses were applied to assess the risk of CP development across groups with different baseline NAFLD and NFS status.ResultsNAFLD participants with high NFS had higher risk of CP compared to non-NAFLD participants (adjusted hazard ratio 1.68, 95% confidence interval [CI] 1.43–1.96, p < .001). Progression from NAFLD free and NAFLD with low NFS to NAFLD with high NFS are associated with 1.56-fold (95% CI 1.21–2.01, p = .001) and 1.43-fold (95% CI 1.11-1.84, p = .006) increased risk of CP, respectively. Risk factors associated with CP vary based on baseline NAFLD and NFS status. Among NAFLD participants with high NFS, hypertension is the only significant risk factor after adjustment for other potential influencing factors.ConclusionsNAFLD and liver fibrosis status can be an independent predictor for CP development regardless of metabolic abnormalities. Hypertension is a major risk factor for CP development among NAFLD patients with high NFS.

KEY MESSAGES

• Non-alcoholic fatty liver disease (NAFLD) and liver fibrosis status can be an independent predictor for development of carotid plaque.
• Progression from NAFLD free and NAFLD with low NAFLD fibrosis score (NFS) to NAFLD with high NFS are associated with increased risk of carotid plaque.
• Risk factors associated with carotid plaque vary based on baseline NAFLD and NFS status, and hypertension plays the most important role among patients with NAFLD and high NFS.

     

Potential value of circulatory microRNA10b gene expression and its target E‐cadherin as a prognostic and metastatic prediction marker for breast cancer

BackgroundBreast cancer (BC) is the leading cause of cancer death in women worldwide. Most BC studies on candidate microRNAs were tissue specimen based. Recently, there has been a focus on the study of cell‐free circulating miRNAs as promising biomarkers in (BC) diagnosis and prognosis. Therefore, we aimed to investigate the circulating levels of miR‐10b and its target soluble E‐ cadherin as potentially easily accessible biomarkers for breast cancer.MethodsSixty‐one breast cancer patients and forty‐eight age‐ and sex‐matched healthy volunteers serving as a control group were enrolled in the present study. Serum samples were used to assess miRNA10b expression by TaqMan miRNA assay technique. In addition, soluble E‐cadherin expression level in serum was determined using ELISA technique.ResultCirculating miR‐10b expression level and serum sE‐cadherin was significantly upregulated in patients with BC compared to controls. Moreover, serum miR‐10b displayed progressive up‐regulation in advanced stages with higher level in metastatic compared to non‐metastatic BC. Additionally, the combined use of both serum miR‐10b and sE‐cadherin revealed the highest sensitivity and specificity for detection of BC metastasis (92.9% and 97.9% respectively) with an area under curve (AUC) of 0.98, 95% CI (0.958–1.00).ConclusionOur data suggest that circulating miR‐10b could be utilized as a potential non‐invasive serum biomarker for diagnosis and prognosis of breast cancer with better performance to predict BC metastasis achieved on measuring it simultaneously with serum sE‐cadherin. Further studies with a large cohort of patients are warranted to validate the serum biomarker for breast cancer management.     

Critical need for pharmacologic treatment options in NAFLD: A pediatric perspective

Nonalcoholic fatty liver disease (NAFLD) affects up to 70% of children with obesity and has become the number one etiology for liver transplant in the United States. Early, effective intervention is critical to prevent disease progression into adulthood. Yet, it is seldom achieved through lifestyle modification alone. Thus, children must be included in NAFLD pharmacology trials, which, to date, continue to focus primarily on adult populations. This commentary serves as a call to action.

Three hundred forty million children worldwide are affected by overweight/obesity (https://www.who.int/end‐childhood‐obesity/publications/taking‐action‐childhood‐obesity‐report/en/). Without intervention, > 75% of these children will continue to gain excessive weight and become adults with obesity. ¹ Alarmingly, almost all adults with obesity (90%) develop comorbid nonalcoholic fatty liver disease (NAFLD), the leading etiology for liver transplant in the United States. ² Thus, effective, early life intervention is critical for children with obesity, up to 70% of whom already have comorbid NALFD by adolescence. ² Lifestyle modifications (e.g., diet and exercise) resulting in weight loss of as little as one kilogram can improve NAFLD in children. ³ However, overall adherence to lifestyle modification is low, with the exception of a few pediatric research studies that offer intense follow‐up ³ , ⁴ or comprehensive in‐home services. ⁴ As such, bariatric surgery is increasingly recognized as an option for weight reduction in children, but it is invasive and there is an unpredictable subset of patients who experience worsening liver fibrosis and NAFLD progression postsurgery. ⁵ This leaves a critical, unmet need for effective pharmacologic interventions in pediatric NAFLD.Currently, there are no approved medications for NAFLD; however, the landscape of potential therapeutic agents is evolving rapidly and showing promise, as highlighted in a comprehensive review by Attia et al. published in Clinical and Translational Science. ⁶ In addition to the many novel therapeutic agents discussed (e.g., obeticholic acid, fibroblast growth factor 19 and 21 analogues, thyroid hormone receptor‐β agonists, etc.), the authors briefly mention past therapeutic experiences with medications already on the market for other clinical indications. Although the adult experience with some of these medications was equivocal, it is important to note that some agents show promise for repurposing in pediatric NAFLD.One example is metformin, a drug already approved for the treatment of type 2 diabetes in children > 10 years of age. In a study of lifestyle modifications combined with either metformin or placebo in children with obesity and insulin resistance ± NAFLD, the metformin group demonstrated a significant decrease in NAFLD scores and NAFLD prevalence, whereas the placebo group experienced an increase from baseline for both. ⁷ Interestingly, when metformin was administered at lower doses in other pediatric trials, it demonstrated isolated improvement in histopathology features (e.g., hepatic ballooning), ⁸ but not in the overall histopathology NAFLD score, suggesting that metformin’s effect on NAFLD may be dose dependent. Therefore, further studies of metformin in the setting of pediatric NAFLD are indicated.Other drugs already approved for obesity‐related comorbidities may also be of interest for repurposing in pediatric NAFLD. Statins, cholesterol‐lowering agents prescribed to patients with obesity and hypercholesterolemia, have been shown to significantly improve hepatic function in patients with obesity and NAFLD ⁹ —presumably through anti‐inflammatory mechanisms in the liver. Although no data are available in pediatrics, in adults with NAFLD, statin therapy is well‐tolerated, with low frequency of hepatotoxicity similar to placebo, ⁹ making statins intriguing drug candidates to consider for the treatment of pediatric NAFLD. Secondary analyses of off‐target treatment effects of medications already prescribed to children with obesity (e.g., statins and metformin) may be helpful in uncovering important insights into therapeutic options for pediatric NAFLD treatment. Especially while best practices for expanding novel NAFLD therapeutics trials to pediatrics remain under development, as referenced in a recent draft guidance from the US Food and Drug Administration (https://www.fda.gov/media/119044/download).In our opinion, and the opinion of other experts, ¹⁰ inclusion of pediatric populations in adult NAFLD pharmacology trials is important and represents a strategy that has been successfully implemented in oncology trials. Yet, the majority of new NAFLD agents continue to be pursued more aggressively for adults than children. As illustrated in the review by Attia et al., ⁶ only 2 of the 17 therapeutic trials discussed included children. By excluding children, we are missing a critical opportunity for early intervention to prevent NAFLD progression from simple hepatic steatosis to more advanced disease (i.e., steatohepatitis, fibrosis, cirrhosis, hepatocellular carcinoma, and end‐stage liver failure). Our hope is that increased awareness of pediatric NAFLD prevalence, coupled with the National Institutes of Health policy for inclusion of research subjects across the lifespan (https://grants.nih.gov/policy/inclusion/lifespan.html), will encourage investigators to include pediatric patients in clinical trials of NAFLD therapeutics.Inclusion of children in pharmacology trials comes with its own set of unique challenges and nuances (e.g., ontogeny, age‐appropriate outcome measures, parental informed consent and informed assent of minors, etc.), beyond the scope of this commentary and as comprehensively reviewed in a pediatric tutorial guide by Shakhnovich et al. ¹¹ In addition, to facilitate inclusion of children specifically in pharmacology trials for NAFLD, NAFLD‐specific noninvasive biomarkers are urgently needed. The majority of studies reviewed by Attia et al. ⁶ relied on histopathology‐based assessment of NAFLD as a therapeutic outcome measure. However, liver biopsy is invasive and histopathology assessment is not always feasible or ethical in children, especially in the context of research. Alanine aminotransferase, the most commonly utilized clinical serum biomarker of liver injury is nonspecific for NAFLD. Therefore, several more‐specific biomarkers are currently under investigation; among them, serum bile acids. Total fasting and postprandial bile acids, and the ratios of conjugated and secondary bile acids, are consistently higher in the sera of adults with nonalcoholic hepatic steatosis, compared with healthy controls. ¹² Pediatric studies of bile acids lag behind, are sparse and inconsistent, and are needed to establish minimally invasive biomarkers of NAFLD for children.Recently, noninvasive liver imaging biomarkers have become more widely available, and it is encouraging to see these modalities incorporated into NAFLD therapeutics research, including four trials discussed by Attia et al. ⁶ Both ultrasound elastography and magnetic resonance elastography can quantify liver stiffness as a noninvasive surrogate for liver fibrosis. However, NAFLD presents a challenge to both techniques because elastography values are affected by both fat and fibrosis. Magnetic resonance proton density fat fraction (MR‐PDFF) can directly estimate hepatic fat content and allows clinicians and researchers to separate the individual contributions from fat vs. fibrosis to liver stiffness. However, MR‐PDFF is only available in specialized tertiary care centers and is expensive. Ultrasound techniques for fat quantification could offer a cheaper, more readily available alternative to MR‐PDFF and these techniques are likely to become widely available in the near future.Thus, the landscape of therapeutic pharmacology trials for NAFLD is rapidly evolving. The advent of noninvasive biomarkers for monitoring NAFLD treatment response offers promise and opportunity, especially for inclusion of pediatric patients in research. A concerted effort must be made to include children in NAFLD pharmacology trials, as NAFLD affects up to 70% of children with obesity, ² and early childhood intervention is key to minimize/reverse disease progression to end‐stage liver disease in adulthood.     

Association between SP‐A rs1965708 gene polymorphism and allergic rhinitis risk in Chinese population

BackgroundPulmonary surfactant protein A (SP‐A) in the respiratory tract plays an important role in host. In the present, we assessed the association between SP‐A gene polymorphism and allergic rhinitis.MethodsUsing a case–control design, we compared the genotype frequencies of SP‐A rs1965708 between allergic rhinitis patients and healthy control group. Genotyping was performed using real‐time quantitative PCR‐based molecular identification methods. Univariate and multivariate logistic regression were performed to quantitatively assess the association between rs1965708 polymorphism and allergic rhinitis, and the odds ratio (OR) and 95% confidence interval (CI) were also calculated.Results500 patients with allergic rhinitis and 500 healthy controls were included in the study. Compared with the CC genotype, we found that AA genotype of rs1965708 could increase the allergic rhinitis risk in the univariate analysis (OR = 2.63, 95% CI: 1.56–4.54, p = 0.000). For dominant model, we found no significant difference in the dominant model (OR = 1.14, 95% CI: 0.86–1.52, p = 0.367). In the recessive model, the CC genotype could elevate the risk of allergic rhinitis compared with CC + AA genotype (OR = 2.70, 95% CI: 1.61–4.54, p = 0.000). Similar results were also found in the allele model (OR = 1.28, 95% CI: 1.07–1.54, p = 0.008). Interactions between rs1965708 AA or AC and smoking increased the allergic rhinitis risk.ConclusionsThe rs1965708 variants of SP‐A gene polymorphism are associated with allergic rhinitis, and the A allele could increase the allergic rhinitis risk. The AA SNP variants that interact with smoking may alter the susceptibility to allergic rhinitis.     

Metabolic Syndrome and COVID-19 Mortality Among Adult Black Patients in New Orleans

OBJECTIVECoronavirus disease 2019 (COVID-19) mortality is high in patients with hypertension, obesity, and diabetes. We examined the association between hypertension, obesity, and diabetes, individually and clustered as metabolic syndrome (MetS), and COVID-19 outcomes in patients hospitalized in New Orleans during the peak of the outbreak.RESEARCH DESIGN AND METHODSData were collected from 287 consecutive patients with COVID-19 hospitalized at two hospitals in New Orleans, LA, from 30 March to 5 April 2020. MetS was identified per World Health Organization criteria.RESULTSAmong 287 patients (mean age 61.5 years; female, 56.8%; non-Hispanic Black, 85.4%), MetS was present in 188 (66%). MetS was significantly associated with mortality (adjusted odds ratio [aOR] 3.42 [95% CI 1.52–7.69]), intensive care unit requirement (ICU) (aOR 4.59 [CI 2.53–8.32]), invasive mechanical ventilation (IMV) (aOR 4.71 [95% CI 2.50–8.87]), and acute respiratory distress syndrome (ARDS) (aOR 4.70 [95% CI 2.25–9.82]) compared with non-MetS. Multivariable analyses of hypertension, obesity, and diabetes individually showed no association with mortality. Obesity was associated with ICU (aOR 2.18 [95% CI 1.25–3.81]), ARDS (aOR 2.44 [95% CI 1.28–4.65]), and IMV (aOR 2.36 [95% CI 1.33–4.21]). Diabetes was associated with ICU (aOR 2.22 [95% CI 1.24–3.98]) and IMV (aOR 2.12 [95% CI 1.16–3.89]). Hypertension was not significantly associated with any outcome. Inflammatory biomarkers associated with MetS, CRP and lactate dehydrogenase (LDH), were associated with mortality (CRP [aOR 3.66] [95% CI 1.22–10.97] and LDH [aOR 3.49] [95% CI 1.78–6.83]).CONCLUSIONSIn predominantly Black patients hospitalized for COVID-19, the clustering of hypertension, obesity, and diabetes as MetS increased the odds of mortality compared with these comorbidities individually.     

Low serum level of apolipoprotein A1 may predict the severity of COVID‐19: A retrospective study

BackgroundDyslipidemia has been observed in patients with coronavirus disease 2019 (COVID‐19). This study aimed to investigate blood lipid profiles in patients with COVID‐19 and to explore their predictive values for COVID‐19 severity.MethodsA total of 142 consecutive patients with COVID‐19 were included in this single‐center retrospective study. Blood lipid profile characteristics were investigated in patients with COVID‐19 in comparison with 77 age‐ and gender‐matched healthy subjects, their predictive values for COVID‐19 severity were analyzed by using multivariable logistic regression analysis, and their prediction efficiencies were evaluated by using receiver operator characteristic (ROC) curves.ResultsThere were 125 and 17 cases in the non‐severe and severe groups, respectively. Total cholesterol (TC), high‐density lipoprotein cholesterol (HDL‐C), low‐density lipoprotein cholesterol (LDL‐C), and apolipoprotein A1 (ApoA1) gradually decreased across the groups in the following order: healthy controls, non‐severe group, and severe group. ApoA1 was identified as an independent risk factor for COVID‐19 severity (adjusted odds ratio [OR]: 0.865, 95% confidence interval [CI]: 0.800–0.935, p < 0.001), along with interleukin‐6 (IL‐6) (adjusted OR: 1.097, 95% CI: 1.034–1.165, p = 0.002). ApoA1 exhibited the highest area under the ROC curve (AUC) among all single markers (AUC: 0.896, 95% CI: 0.834–0.941); moreover, the risk model established using ApoA1 and IL‐6 enhanced prediction efficiency (AUC: 0.977, 95% CI: 0.932–0.995).ConclusionBlood lipid profiles in patients with COVID‐19 are quite abnormal compared with those in healthy subjects, especially in severe cases. Serum ApoA1 may represent a good indicator for predicting the severity of COVID‐19.     

A trauma‐related survival predictive model of acute respiratory distress syndrome

PurposeThe purpose of this study was to construct and validate a simple model for the prediction of survival in patients with trauma‐related ARDS.MethodsThis is a single‐center, retrospective cohort study using MIMIC‐III Clinical Database.Results842 patients were included in this study. 175 (20.8%) died in‐hospital, whereas 215 (25.5%) died within 90 days. The deceased group had higher Acute Physiology Score (APS III), Sequential Organ Failure Assessment (SOFA), and Simplified Acute Physiology Score II (SAPS II). In multivariate logistic regression model, independent risk factors for mortality in ARDS patients included age ([odds ratio] OR, 1.035; 95% confidence interval [CI], 1.020–1.049), body mass index (OR, 0.957; 95% CI, 0.926–0.989), red blood cell distribution width (OR, 1.283; 95% CI, 1.141–1.443), hematocrit (OR, 1.055; 95% CI, 1.017–1.095), lactate (OR, 1.226; 95% CI, 1.127–1.334), blood urea nitrogen (OR, 1.025; 95% CI, 1.007–1.044), acute kidney failure (OR, 1.875; 95% CI, 1.188–2.959), sepsis (OR, 1.917; 95% CI, 1.165–3.153), type of admission (emergency vs. elective [OR, 2.822; 95% CI, 1.647–4.837], and urgent vs. elective [OR, 5.156; 95% CI, 1.896–14.027]). The area under the curve (AUC) of the model was 0.826, which was superior than the SAPS II (0.776), APS III (0.718), and SOFA (0.692). In the cross‐validation model, the accuracy of the test set was 0.823, the precision was 0.643, and the AUC was 0.813.ConclusionsWe established a prediction model using data commonly used in the clinic, which has high accuracy and precision and is worthy of use in clinical practice.     

Associations of CYP2B6 genetic polymorphisms with Hirschsprung’s disease in a southern Chinese population

BackgroundHirschsprung’s disease (HSCR) is an enteric nervous system birth defect partially caused by a genetic disorder. Single‐nucleotide polymorphisms (SNPs) of the cytochrome P450 family 2 subfamily B member 6 (CYP2B6) gene are reported to be associated with HSCR.MethodsWe evaluated the association of rs2054675, rs707265, and rs1042389 with HSCR susceptibility in southern Chinese children including 1470 HSCR patients and 1473 controls using the TaqMan SNP Genotyping Assay.Resultsrs2054675 C allele and the rs707265 G allele were risk SNPs for total colonic aganglionosis (OR = 1.82, 95% CI 1.29 ~ 2.55, P_adj < 0.001 and OR = 0.68, 95% CI 0.48 ~ 0.97, P_adj = 0.034). These results suggested that CYP2B6 rs2054675 and rs707265 polymorphisms were associated with increased susceptibility to the severe HSCR subtype in southern Chinese children.ConclusionWe suggest that CYP2B6 rs2054675 and rs707265 polymorphisms are associated with increased susceptibility to the severe HSCR subtype in southern Chinese children.