Serum gasdermin D levels are associated with the chest computed tomography findings and severity of COVID-19

BackgroundThe role of programmed cell death, especially pyroptosis and apoptosis, in unfavorable immune responses in COVID-19 remains to be elucidated.MethodsWe conducted a cross-sectional analysis to investigate the association between the serum gasdermin D (GSDMD) levels, a pyroptotic marker, and caspase-cleaved cytokeratin 18 fragment (M30), an apoptotic marker, and the clinical status and abnormal chest computed tomography (CT) findings in patients with COVID-19.ResultsIn this study, 46 patients diagnosed with COVID-19 were divided into the following three groups according to the disease severity: mild to moderate group (n = 10), severe group (n = 14), and critical group (n = 22). The serum GSDMD levels were higher in the critical group than in the mild to moderate group (P = 0.016). In contrast, serum M30 levels were lower in the critical group than in the severe group (P = 0.048). Patients who required mechanical ventilation or died had higher serum GSDMD levels than those who did not (P = 0.007). Area of consolidation only and of ground glass opacity plus consolidation positively correlated with serum GSDMD levels (r = 0.56, P < 0.001 and r = 0.53, P < 0.001, respectively).ConclusionHigher serum GSDMD levels are associated with critical respiratory status and the consolidation area on chest CT in patients with COVID-19, suggesting that excessive activation of pyroptosis may affect the clinical manifestations in patients with COVID-19.     

Predictive factors for the long-term use of pirfenidone in patients with fibrosing interstitial lung disease

BackgroundPirfenidone is an anti-fibrotic agent approved for idiopathic pulmonary fibrosis (IPF), and long-term treatment data and the effect of continuation after disease progression have been reported. The efficacy and safety of pirfenidone in fibrosing interstitial lung disease (ILD) patients without IPF have been recently reported in clinical trials; therefore, the benefits of long-term treatment are also expected. This study aims to analyze the long-term treatment data of pirfenidone and clarify the predictive factors for long-term use of pirfenidone in non-IPF patients.MethodsWe retrospectively reviewed the records of consecutive fibrosing ILD patients who started using pirfenidone between 2008 and 2014.ResultsOf the 266 fibrosing ILD patients, 167 patients had IPF, and 99 had non-IPF. Despite the non-significant differences in body size and pulmonary function between IPF and non-IPF patients, the non-IPF patients had better overall survival than the IPF patients (median 4.06 years vs. 2.09 years, p < 0.0001). In addition, the non-IPF patients had a significantly longer time to treatment discontinuation than the IPF patients (median 2.20 years vs. 1.20 years, p = 0.002). Multivariate logistic regression analysis for ≥2 years of use of pirfenidone showed that the percent predicted forced vital capacity (%FVC) and age were predictive factors common to both IPF and non-IPF patients.ConclusionsOur results indicate that non-IPF patients can continue using pirfenidone for longer durations than IPF patients. Initiation of pirfenidone for fibrosing ILD patients with higher %FVC and younger age would lead to long-term use of pirfenidone.     

Clinical features of chronic summer-type hypersensitivity pneumonitis and proposition of diagnostic criteria

BackgroundTrichosporon asahii (T. asahii) causes chronic summer-type hypersensitivity pneumonitis (C-SHP); however, little is known about the clinical features of this condition. We aimed to elucidate the clinical features of C-SHP and propose practical diagnostic criteria for C-SHP based on the presence of serum anti-T. asahii antibody (TaAb).MethodsPatients diagnosed with C-SHP and idiopathic pulmonary fibrosis (IPF) between January 2010 and May 2017 were reviewed retrospectively. Clinical findings were compared between the two groups. Criteria for C-SHP were proposed on the basis of significant characteristics and applied to the development and validation cohorts.ResultsThirty-one patients with C-SHP and 26 with TaAb-negative IPF were identified. C-SHP patients were more likely to live in wooden houses; their serum Krebs von den Lungen-6 (KL-6) and serum surfactant protein-D (SP-D) levels were higher than those of IPF patients. C-SHP patients were more likely to have subpleural consolidation, micronodules, and extensive ground-glass opacification on high-resolution computed tomography (HRCT). The following 3 items were considered to have diagnostic value: I) TaAb positivity; II) an HRCT pattern consistent with chronic hypersensitivity pneumonitis, including mosaic attenuation or micronodules; and III) elevated serum biomarker levels (KL-6 > 1500 U/mL or SP-D > 250 ng/mL). We defined cases satisfying I) and II) as “probable C-SHP” and those satisfying all 3 criteria as “confident clinical diagnosis of C-SHP”. The areas under the receiver-operating curve were 0.965 and 0.993 in the development and validation cohorts, respectively, which suggested that these criteria had good discriminative ability in clinical evaluations.ConclusionsClinical features could be useful for distinguishing C-SHP from IPF and other etiologies of ILDs.     

A modified GAP model for East-Asian populations with idiopathic pulmonary fibrosis

BackgroundThe easy-to-calculate gender, age, and lung physiology (GAP) model shows good predictive and discriminative performance in the prognosis of idiopathic pulmonary fibrosis (IPF). However, the GAP model was not effective in predicting the prognosis accurately in previous Japanese and Korean IPF cohort studies. Therefore, we developed a modified GAP model for the East-Asian populations by weighing the GAP variables. The validity of the modified GAP model was subsequently evaluated in East-Asian IPF patients.MethodsThe derivation cohort comprised 326 patients with IPF. Weights of the variables were adjusted on the basis of coefficients derived from Cox regression models. The total points were distributed to the three stages of the disease so that the number of patients included in each stage was appropriate. The validity of the modified model was analyzed in another Japanese cohort of 117 patients with IPF and a nationwide cohort of Korean patients with IPF.ResultsPredicted survival rates differed significantly in the derivation cohort using the modified GAP model for each stage of IPF (log-rank test: stage I vs. stage II, p < 0.001; stage II vs. stage III, p < 0.001). Model performance improved according to Harrell's C-index (at three years: 0.696 in the original GAP model to 0.738 in the modified model). The performance of the modified model was validated in the Japanese validation and Korean national cohorts.ConclusionsOur modification of the original GAP model showed improved performance in East-Asian IPF patient populations.     

Serum uric acid is associated with incident metabolic syndrome independent of body shape index and body roundness index in healthy individuals

Background and aimsElevated serum uric acid (SUA) levels, body shape index (BSI) and body roundness index (BRI) were associated with incident metabolic syndrome (MetS). We aimed to investigate the relationship among the SUA level, BSI, and BRI on the incidence of MetS.Methods and resultsWe retrospectively included 6221 healthy individuals from annual health exams at our hospital between 2016/1/1 and 2016/12/31. We defined hyperuricemia as SUA levels greater than 7 mg/dl in men and 6 mg/dl in women and MetS according to the contemporary definition. The study cohort included 6221 healthy individuals with an overall incidence rate of MetS of 9.8%. Compared with the normouricemic group, the hyperuricemic group had a greater incidence of MetS (17.2% vs. 9.6%, P < 0.001). After full adjustment for confounders, the SUA level was significantly associated with incident MetS in addition to body mass index (BMI) (adjusted OR [aOR]: 1.161, 95% CI: 1.071–1.259, P < 0.001), BRI (aOR: 1.196, 95% CI: 1.104–1.296, P < 0.001), and BSI (aOR: 1.297, 95% CI: 1.200–1.403, P < 0.001). Regarding the anthropometric indices, BMI and BRI were independent predictors of incident MetS, but the BSI lost its significant association in multivariate logistic regression analyses. In sensitivity analyses, various thresholds of elevated SUA levels remained associated with incident MetS.ConclusionWe showed a dose-response effect of SUA on incident MetS independent of BMI, BRI and BSI in healthy individuals. Future studies can use SUA levels to stratify cardiometabolic risk in healthy individuals.Clinical trialsClinicalTrials.gov with the identification number NCT03473951.     

Incidence and changes in treatment of acute exacerbation of idiopathic pulmonary fibrosis in Japan: A claims-based retrospective study

BackgroundAcute exacerbation is an essential prognostic factor in idiopathic pulmonary fibrosis (IPF) and is the leading cause of death in Japanese patients with IPF. Its epidemiology, treatment status, and effect on IPF progression have been insufficiently investigated. We examined the incidence of acute exacerbation and treatment status before and after the onset of acute exacerbation in Japanese patients with IPF to provide basic information for treatment strategies.MethodsA Japanese claims database (April 2008–March 2019) from acute-care hospitals was analyzed. Incidence of acute exacerbation, time to the next event, and percentages of patients who received each treatment by the year before and after the onset of acute exacerbation were examined in patients diagnosed with IPF at least once. Acute exacerbation was defined according to the use of steroid pulse therapy.ResultsWe identified 9961 patients with IPF and 2629 acute exacerbations (average age at the time of acute exacerbation: 74.8 years, percentage of men: 79%). The annual incidence of acute exacerbation was approximately 10% between 2010 and 2018. The time to the next acute exacerbation shortened with increasing number of these events. The percentage of patients receiving antifibrotic drugs remained constant (30%–40%) throughout the period. The percentages of patients receiving steroid therapy, immunosuppressive drugs, and oxygen therapy increased after the onset of acute exacerbation compared with before the onset.ConclusionsThe annual incidence of acute exacerbation was approximately 10% in recent years. It is suggested that acute exacerbation worsens respiratory function in patients with IPF.     

Metabolic abnormalities,but not obesity per se,associated with chronic kidney disease in a Taiwanese population

Background and aimsIt is inconclusive whether obesity itself or metabolic abnormalities are linked to chronic kidney disease (CKD). The aim of this study was to examine the association between different subtypes of obesity and metabolic abnormalities with CKD in adults.Methods and resultsThis study enrolled 14,983 eligible subjects stratified into metabolically healthy normal weight (MHNW), metabolically healthy overweight (MHOW), metabolically healthy obesity (MHO), metabolically unhealthy normal weight (MUNW), metabolically unhealthy overweight (MUOW), and metabolically unhealthy obesity (MUO) according to body mass index and metabolic syndrome status (ATP-III criteria). The metabolic healthy phenotype was defined as the absence of both metabolic syndrome and any known diabetes, coronary artery disease, stroke, hypertension or dyslipidemia. Early and advanced CKD were defined as eGFR<60, proteinuria, or structural abnormalities as detected by renal sonography. The prevalence of CKD was 2.5, 3.0, 4.0, 10.6, 9.5, and 10.5% in subjects with MHNW, MHOW, MHO, MUNW, MUOW, and MUO, respectively. In the multivariate analysis, the MUNW (OR:2.22, P < 0.001), MUOW (OR:2.22, P < 0.001), and MUO (OR:2.45, P < 0.001) groups were associated with early CKD. For advanced CKD, the OR was 2.56 (P < 0.001), 2.31 (P < 0.001), and 3.49 (P < 0.001) in the MUNW, MUOW, and MUO groups, respectively. The associated risks of early and advanced CKD were not significant in the MHOW and MHO group. MUOW and MUO were associated with higher risk of CKD compared with MHOW and MHO after adjusting other variables.ConclusionsMetabolic abnormalities, but neither overweight nor obesity, were associated with a higher risk of CKD in adults.     

Abundant TNF-LIGHT expression in the airways of patients with asthma with persistent airflow limitation: Association with nitrative and inflammatory profiles

BackgroundThe role of the inflammatory secretory protein TNF-LIGHT (LIGHT) in the molecular mechanisms underlying persistent airflow limitation (PAL) in asthma remains unclear. We hypothesized that high airway LIGHT expression may be a feature of asthma with PAL associated with specific expression patterns of inflammatory molecules.MethodsThis hypothesis was tested in 16 patients with asthma on inhaled corticosteroid treatment. Induced sputum was collected, the expression of LIGHT and 3-nitrotyrosine (NT), which reflects the footprint of reactive nitrogen species content, was measured using immunohistochemical staining, and the inflammatory molecules in the sputum supernatant were analyzed using a magnetic bead array.ResultsLIGHT staining in the cells had a significantly higher intensity in participants with PAL than in participants without PAL (47.9 × 10⁴/ml vs. 5.4 × 10⁴/ml; p < 0.05). The array analysis indicated that IL-8, IL-19, matrix metalloproteinase 2, and osteopontin, were associated with high LIGHT immunoreactivity. The fractionation of 3-NT-positive cells was positively correlated with that of LIGHT-positive cells (r = 0.57, p < 0.05) and the TGF-β1 level (r = 0.61, p < 0.05). LIGHT- and 3-NT-positive cells showed significant positive correlation with the differential cell counts of neutrophils, macrophages, and eosinophils in the induced sputum. Intense immunoreactivities of LIGHT (r = −0.54, p < 0.05) and 3-NT (r = −0.42, p = 0.1) were negatively associated with decreased forced expiratory volume in 1/forced vital capacity ratio.ConclusionsThe findings suggest that LIGHT is a key component in the association between airway inflammation and airflow limitation in patients with asthma, and its expression may be persistently correlated with the abundance of inflammatory cells and inflammatory and profibrogenic radical/molecules.     

Extent of pulmonary fibrosis on high-resolution computed tomography is a prognostic factor in patients with pleuroparenchymal fibroelastosis

BackgroundSeveral prognostic factors for pleuroparenchymal fibroelastosis (PPFE) have recently been reported. However, detailed high-resolution computed tomography (HRCT) findings have not yet been evaluated as prognostic factors. This study retrospectively investigated whether HRCT findings are prognostic factors in patients with PPFE compared to those with idiopathic pulmonary fibrosis (IPF).MethodsPatients with PPFE and IPF diagnosed at our hospital between January 2008 and December 2016 were enrolled. Clinical and HRCT characteristics were obtained. In addition to our patients, we also analyzed data of PPFE patients whose cause of death had been identified in previous studies.ResultsWe enrolled 15 patients with PPFE and 75 patients with IPF. Consolidation and maximum pleural thickening were significantly higher in patients with PPFE than in those with IPF (both P < .001). Fibrosis score, honeycomb area, and traction bronchiectasis were not significantly different between these patient groups but were significant prognostic factors in patients with PPFE in univariate analysis (P = .021, P = .017, and P = .014, respectively). The proportions of deaths by acute exacerbation or lung cancer were significantly lower in patients with PPFE than in those with IPF (P < .001 and P = .001, respectively), whereas death by respiratory failure was significantly more frequent in PPFE patients (P < .001).ConclusionsHRCT findings, such as fibrosis score, honeycomb area, and traction bronchiectasis, were independent prognostic factors in patients with PPFE. Respiratory failure, but not acute exacerbation and lung cancer, was the main cause of death in patients with PPFE.     

Identification of genetic loci simultaneously associated with multiple cardiometabolic traits

Background and aimsCardiometabolic disorders (CMD) arise from a constellation of features such as increased adiposity, hyperlipidemia, hypertension and compromised glucose control. Many genetic loci have shown associations with individual CMD-related traits, but no investigations have focused on simultaneously identifying loci showing associations across all domains. We therefore sought to identify loci associated with risk across seven continuous CMD-related traits.Methods and resultsWe conducted separate genome-wide association studies (GWAS) for systolic and diastolic blood pressure (SBP/DBP), hemoglobin A1c (HbA1c), low- and high- density lipoprotein cholesterol (LDL-C/HDL-C), waist-to-hip-ratio (WHR), and triglycerides (TGs) in the UK Biobank (N = 356,574–456,823). Multiple loci reached genome-wide levels of significance (N = 145–333) for each trait, but only four loci (in/near VEGFA, GRB14-COBLL1, KLF14, and RGS19-OPRL1) were associated with risk across all seven traits (P < 5 × 10^?8). We sought replication of these four loci in an independent set of seven trait-specific GWAS meta-analyses. GRB14-COBLL1 showed the most consistent replication, revealing nominally significant associations (P < 0.05) with all traits except DBP.ConclusionsOur analyses suggest that very few loci are associated in the same direction of risk with traits representing the full spectrum of CMD features. We identified four such loci, and an understanding of the pathways between these loci and CMD risk may eventually identify factors that can be used to identify pathologic disturbances that represent broadly beneficial therapeutic targets.     

Treatment efficacy of LAMA versus placebo for stable chronic obstructive pulmonary disease: A systematic review and meta-analysis

BackgroundFour long-acting muscarinic antagonists (LAMAs), tiotropium, glycopyrronium, aclidinium, and umeclidinium, are currently available for the treatment of stable chronic obstructive pulmonary disease (COPD). However, no integrated analysis has sought to determine the effectiveness of these LAMAs. Thus, we conducted a systematic review and meta-analysis to evaluate the efficacy and safety of LAMA versus placebo in patients with stable COPD.MethodsA literature search of relevant randomized control trials that administered LAMA to stable COPD patients was conducted, and the exacerbations, quality of life (QoL), dyspnea score, lung function, and adverse event of patients were evaluated.ResultsA total of 33 studies were included in this meta-analysis. LAMA significantly decreased the frequency of exacerbations compared to the placebo (OR 0.75; 95% CI 0.66 to 0.85; P < 0.001). The mean changes in the St George's Respiratory Questionnaire score (mean difference, ?3.61; 95% CI, ?4.27 to ?2.95; P < 0.00001), transitional dyspnea index score (mean difference 1.00; 95% CI 0.83 to 1.17; P < 0.00001), and trough FEV₁ (mean difference 0.12; 95% CI 0.11 to 0.13; P < 0.0001) indicated significantly greater improvement in the LAMA group than the placebo group. The number of withdrawals due to adverse events in the LAMA group was significantly fewer than that in the placebo group (OR -0.02; 95% CI -0.03 to ?0.01; P = 0.002).ConclusionLAMA is superior to placebo due to lower frequency of exacerbations and adverse events, as well as higher trough FEV₁, QoL, and dyspnea score for stable COPD.     

Differential Relapse Patterns After Discontinuation of Entecavir vs Tenofovir Disoproxil Fumarate in Chronic Hepatitis B

Background and AimsWhether entecavir (ETV) and tenofovir disoproxil fumarate (TDF) differentially affect relapse and outcomes following treatment discontinuation across different patient subpopulations remains unclear. We aimed to compare rates of off-therapy hepatitis B surface antigen (HBsAg) loss, virological and clinical relapse, and retreatment between chronic hepatitis B (CHB) patients who discontinued TDF or ETV therapy.MethodsThis study included 1402 virally suppressed CHB patients who stopped either ETV (n = 981) or TDF (n = 421) therapy between 2001 and 2020 from 13 participating centers across North America, Europe, and Asia. All patients were hepatitis B e antigen–negative at treatment discontinuation. Inverse probability of treatment weighting was used to balance the treatment groups. Outcomes were analyzed using survival methods.ResultsDuring a median off-treatment follow-up of 18 months, HBsAg loss occurred in 96 (6.8%) patients overall. Compared with ETV, TDF was associated with a higher rate of HBsAg loss (P = .03); however, the association was no longer significant after statistical adjustment (P = .61). Virological relapse occurred earlier among TDF-treated patients (P < .01); nonetheless, rates became comparable after the first year off therapy (P = .49). TDF was significantly associated with a higher clinical relapse rate than ETV throughout follow-up (P < .01). The development of a virological or clinical relapse did not affect the rate of HBsAg loss. Retreatment rates were not significantly different between the treatment groups.ConclusionsTDF and ETV have differential relapse patterns but are associated with similar rates of HBsAg loss and retreatment following discontinuation. Finite therapy can be considered for CHB patients on either TDF or ETV therapy.     

First-Phase Ejection Fraction Predicts Response to Cardiac Resynchronization Therapy and Adverse Outcomes

ObjectivesThe aim of this study was to examine the value of first-phase ejection fraction (EF1), to predict response to cardiac resynchronization therapy (CRT) and clinical outcomes after CRT.BackgroundCRT is an important treatment for patients with chronic heart failure. However, even in carefully selected cases, up to 40% of patients fail to respond. EF1, the ejection fraction up to the time of maximal ventricular contraction, is a novel sensitive echocardiographic measure of early systolic function and might relate to response to CRT.MethodsAn initial retrospective study was performed in 197 patients who underwent CRT between 2009 and 2018 and were followed to determine clinical outcomes at King’s Health Partners in London. A validation study (n = 100) was performed in patients undergoing CRT at Barts Heart Centre in London.ResultsVolumetric response rate (reduction in end-systolic volume ≥15%) was 92.3% and 12.1% for those with EF1 in the highest and lowest tertiles (P < 0.001). A cutoff value of 11.9% for EF1 had >85% sensitivity and specificity for prediction of response to CRT; on multivariate binary logistic regression analysis incorporating previously defined predictors, EF1 was the strongest predictor of response (odds ratio [OR]: 1.56 per 1% change in EF1; 95% CI: 1.37-1.78; P < 0.001). EF1 was also the strongest predictor of improvement in clinical composite score (OR: 1.11; 95% CI: 1.04-1.19; P = 0.001). Improvement in EF1 at 6 months after CRT implantation (6.5% ± 5.8% vs 1.8% ± 4.3% in responders vs nonresponders; P < 0.001) was the best predictor of heart failure rehospitalization and death after median follow-up period of 20.3 months (HR: 0.81; 95% CI: 0.73-0.90; P < 0.001). In the validation cohort, EF1 was a similarly 1strong predictor of response (OR: 1.45; 95% CI: 1.23-1.70; P < 0.001) as in the original cohort.ConclusionsEF1 is a promising marker to identify patients likely to respond to CRT.     

1-Year Outcomes of Cardioband Tricuspid Valve Reconstruction System Early Feasibility Study

BackgroundTricuspid regurgitation (TR) is prevalent and undertreated, with mortality and morbidity increasing with TR severity. Given poor outcomes with medical therapy and high in-hospital mortality for isolated tricuspid valve surgery, emerging transcatheter repair devices offer a promising alternative.ObjectivesThe Edwards Cardioband Tricuspid Valve Reconstruction System Early Feasibility study (NCT03382457) evaluates the treatment of functional TR via annular reduction with the Cardioband Tricuspid Valve Reconstruction System (Edwards Lifesciences).MethodsPatients with ≥ moderate functional TR were eligible for this prospective, single-arm multicenter study. At 1 year, patients were evaluated for echocardiographic parameters, clinical and quality-of-life measures, and major adverse events.ResultsThe 37 patients enrolled had a mean age of 78 years; 76% were female; and they had ≥ severe functional (97.3%) or mixed (2.7%) TR, atrial flutter/fibrillation (97%), and New York Heart Association functional class III/IV (65%). At 1 year, 73.0% achieved ≤ moderate TR (P < 0.0001), and 73.1% had ≥2 grade reductions. Echocardiography showed significant reductions in the tricuspid annulus diameter (P < 0.0001), mean vena contracta (P < 0.0001), proximal isovelocity surface area effective regurgitant orifice area (P < 0.0001), right ventricular end-diastolic diameter (P < 0.0001), and inferior vena contracta (P = 0.0006). New York Heart Association functional class improved significantly (P < 0.0001), with 92.3% achieving class I/II, and Kansas City Cardiomyopathy Questionnaire scores improved by 19.0 points (P < 0.0001). One-year cardiovascular mortality was 8.1%, reinterventions were necessary in 5.4%, major access site complications occurred in 8.1%, and severe bleeding was noted in 35.1% of patients. Kaplan-Meier estimates of survival and freedom from heart failure rehospitalization were 85.9% and 88.7%, respectively.ConclusionsOne-year experience using the Cardioband system for tricuspid valve repair shows high survival and low rehospitalization rates with durable outcomes in TR reduction and echocardiographic, clinical, and quality-of-life outcomes.     

Serial 6-month change in forced vital capacity predicts subsequent decline and mortality in Japanese patients with newly diagnosed idiopathic pulmonary fibrosis

BackgroundThe clinical course of idiopathic pulmonary fibrosis (IPF) is characterized by a progressive decline in lung function; however, predicting changes in lung function is difficult. We sought to determine whether the prior 6-month trend in forced vital capacity (FVC) could predict mortality and the subsequent 6-month trend in FVC.MethodsWe retrospectively analyzed consecutive patients with newly diagnosed IPF who underwent serial pulmonary function tests. The immediate two years after the initial evaluation were divided into four terms of six months each and stratified on the basis of presence or absence of a ≥10% relative decline in FVC at six months (declined and stable groups, respectively).ResultsWe included 107 patients with %predicted FVC of 80.8% and %predicted diffusing capacity of the lung for carbon monoxide of 58.9%. In multivariate analysis, a decline in %predicted FVC in the initial six months was found to be an independent prognostic factor (hazard ratio 4.45, 95% confidence interval 2.62–7.56, p < 0.01). Among the 46 terms in which the FVC declined during the initial 1.5-year study period, a decline in FVC was exhibited in 23 (50.0%) of the subsequent terms. Among 231 terms in which FVC remained stable, a decline was observed in 32 (13.9%) of the subsequent terms (relative risk 3.61, p < 0.01). The frequency of FVC decline in each term was 16–27%. FVC was stable or declined in all four terms in 50.5% and 15.9% of cases, respectively.ConclusionsSix-month decline in FVC predicts subsequent FVC change and mortality in IPF patients in the era of antifibrotic agents.     

Effectiveness of the pomegranate extract in improving hepatokines and serum biomarkers of non-alcoholic fatty liver disease: A randomized double blind clinical trial

Background and aimPomegranate as a functional food has various properties and effects on health. The aim of the study was to evaluate the effect of pomegranate extract on serum levels of liver enzymes, hepatokines, interleukin-6 (IL-6), and total antioxidant capacity in non-alcoholic fatty liver disease (NAFLD).MethodsIn this double-blind randomized clinical trial, 44 patients with NAFLD were divided into two groups: pomegranate extract tablets and placebo. The intervention period was 12 weeks. At the beginning and end of the study, serum levels of alanine transaminase (ALT), aspartate transaminase (AST), gamma-glutamyl transferase (GGT), alkaline phosphatase (ALP), fetuin-A, fibroblast growth factor 21 (FGF-21), interleukin-6 (IL-6), and total antioxidant capacity were assessed in both groups.ResultsPomegranate extract reduced the level of ALT (P < 0.001), AST (P < 0.001), GGT (P < 0.001), fetuin-A (P < 0.001), FGF-21(P < 0.001) and IL-6 (P = 0.04) compared to the placebo. Pomegranate extract also led to an increase in total antioxidant capacity (P?0.001) but had no effect on ALP.ConclusionIt seems that the pomegranate extract improves several markers of NAFLD, and can be useful as a treatment supplement.The clinical trial approved by Nutrition and Metabolic Diseases Research Center, Ahvaz Jundishapur University of Medical Sciences (grant No. NRC-9811).Trial registrationIranian Registry of Clinical Trials (IRCT), IRCT20140107016123N14, https://www.irct.ir/trial/42739.     

The prognostic value of the COPD Assessment Test in fibrotic interstitial lung disease

BackgroundThe COPD Assessment Test (CAT) has been studied as a measure of health status in idiopathic pulmonary fibrosis (IPF) and interstitial lung disease associated with connective tissue disease. However, its prognostic value is unknown. The present study explored the association between CAT score and mortality in fibrotic interstitial lung disease (FILD), including IPF and other forms of ILD.MethodsWe retrospectively analyzed 501 consecutive patients with FILD who underwent clinical assessment, including pulmonary function test and CAT. The association between CAT score and 3-year mortality was assessed using Cox proportional hazard analysis, Kaplan–Meier plots, and the log-rank test for trend. To handle missing data, the imputed method was used.ResultsThe patients’ median age was 68 years, and 320 were male (63.9%). Regarding CAT severity, 203 patients had a low impact level (score <10), 195 had a medium level (10–20), 80 had a high level (21–30), and 23 had a very high level (31–40). During the 3-year study period, 118 patients died. After adjusting for age, sex, forced vital capacity, diffusion capacity for carbon monoxide, IPF diagnosis, and usual interstitial pneumonia pattern on high-resolution computed tomography, the CAT score was significantly associated with 3-year mortality (hazard ratio in increments of 10 points: 1.458, 95% confidence interval 1.161–1.830; p < 0.001). In addition, patients with high and very high impact levels had twofold and threefold higher mortality risk than those with low levels, respectively.ConclusionThe CAT has prognostic value in FILD.     

Constructing a metabolic integral score model for the quantification of metabolic dysfunction and tendency

Background and aimsThe binary nature of metabolic syndrome (MetS) cannot quantitatively describe the severity of metabolic abnormalities. We aim to establish a metabolic integral score (MIS) model to quantify the severity and polarity of metabolic disorders and their relationship with insulin sensitivity and secretion.Methods and resultsWe performed factor analysis on 9950 participants from a cross-sectional study conducted in China. The MIS model was established using 10 variables including body mass index (BMI), waist circumference, hip circumference, glycosylated hemoglobin (HbA1c), fasting and 2-h plasma glucose (FPG, 2h-PG), systolic blood pressure (SBP), diastolic blood pressure (DBP), high-density lipoprotein (HDL) and triglyceride (TG) levels. Four common factors were identified as “glucose factor,” “obesity factor,” “blood pressure factor,” and “lipid factor,” respectively, in MIS model (KMO = 0.755, P < 0.001). MIS = 0.433 × Factor 1 + 0.267 × Factor 2 + 0.172 × Factor 3 + 0.128 × Factor 4. Insulin sensitivity and β-cell function decreased with the increase of MIS (P < 0.001). We classified four metabolic tendencies according to factor quartiles. Individuals in Tendency 1 (severe hyperglycemia) had the worst β-cell function. Tendency 3 (severe hypertension) had the best insulin sensitivity. Tendency 4 (severe dyslipidemia) had preferable β-cell function (P < 0.05).ConclusionsOur MIS model provides a quantitative scoring system to assess various patterns of metabolic abnormality that indicate different underlying pathophysiology.     

A systematic review and meta-analysis comparing the clinical characteristics and outcomes of COVID-19 and influenza patients on ECMO

BackgroundExtracorporeal membrane oxygenation (ECMO) is a valuable rescue therapy to treat refractory hypoxemia caused by influenza. The present meta-analysis aimed to compare the clinical characteristics and outcomes of ECMO between COVID-19 and influenza.MethodsWe searched the PubMed, Cochrane Library, SCOPUS, and Web of Science databases from inception to May 1, 2021. The included studies compared the clinical characteristics and outcomes of ECMO between adults with COVID-19 and those with influenza.ResultsThe study included four retrospective cohorts involving a total of 129 patients with COVID-19 and 140 with influenza who were treated using ECMO. Clinical characteristics were similar between the COVID-19 and influenza groups, including body mass index (BMI), diabetes mellitus, hypertension, and immunocompromised status. A higher proportion of patients with COVID-19 on ECMO were male (75.9% vs. 62.9%; P = 0.04). There was no difference between the groups in terms of illness severity based on sequential organ failure assessment (SOFA) score or serum pH. Patients with COVID-19 had a longer mean duration of mechanical ventilation before ECMO (6.63 vs. 3.38 days; P < 0.01). The pooled mortality rate was 43.8%. The mean ECMO duration (14.13 vs. 12.55 days; P = 0.25) and mortality rate (42.6% vs. 45.0%; P = 0.99) were comparable between the groups.ConclusionClinical characteristics, ECMO duration, and mortality were comparable between patients with COVID-19 and those with influenza who required ECMO to treat refractory hypoxemia. The duration of mechanical ventilation before ECMO did not influence outcomes. Patients with COVID-19 benefit from ECMO salvage therapy similarly to those with influenza.     

Structural Cardiac Remodeling in Atrial Fibrillation

ObjectivesThis study sought to evaluate preablation computed tomography angiography (CTA) for atrial and epicardial features to predict atrial fibrillation (AF) recurrence after ablation.BackgroundStructural atrial remodeling is a process associated with occurrence or persistence of AF. Different anatomical imaging features have been proposed to influence atrial remodeling both negatively and positively as substrate for AF.MethodsPatients with nonvalvular AF underwent cardiac CTA before pulmonary vein isolation at 2 high-volume centers. Left atrial (LA) and right atrial volumes, LA wall thickness (LAWT), and epicardial adipose tissue volume and attenuation were evaluated. Additional subanalyses of electroanatomical maps were made. Follow-up was performed for at least 12 months, including subanalysis of repeated cardiac CTA studies. Interrater variability was assessed.ResultsOf 732 patients, 270 (36.9%) had AF recurrence after a mean of 7 months. CT analysis revealed larger indexed LA volume (47.3 mL/m² vs 43.6 mL/m²; P = 0.0001) and higher mean anterior (1.91 mm vs 1.65 mm; P < 0.0001) and posterior (1.61 mm vs 1.39 mm; P = 0.001) LAWT in patients with AF recurrence. Epicardial adipose tissue volume in patients with AF recurrence was higher (144.5 mm³ vs 128.5 mm³; P < 0.0001) and further progressed significantly in a subset of 85 patients after 2 years (+11.8 mm² vs −3.5 mm²; P = 0.041). Attenuation levels were lower, indicating a higher lipid component associated with AF recurrence (−69.1 HU vs −67.5 HU; P = 0.001). A total of 103 atrial voltage maps were highly predictive of AF recurrence and showed good discriminatory power for patients with low voltage >50% and LAWT (1.55 ± 0.5 mm vs 1.81 ± 0.6 mm; P = 0.032). Net reclassification improvement (NRI) showed a significant incremental benefit (NRI = 0.279; P < 0.0001) when adding LAWT to established risk models.ConclusionsAtrial wall thickness, epicardial fat volume, and attenuation are associated with AF recurrence in patients undergoing ablation therapy.