The safety and efficacy of durvalumab consolidation therapy in the management of patients with stage III non-small-cell lung cancer and preexisting interstitial lung disease

BackgroundSome lung cancer patients have preexisting interstitial lung disease (ILD), which is considered a risk factor for lung cancer treatment. This study investigated the safety and efficacy of durvalumab consolidation therapy for patients with stage III non-small-cell lung cancer (NSCLC) and preexisting ILD.MethodsFifty consecutive patients who were judged to be tolerable to concurrent chemoradiotherapy (CCRT) for stage III NSCLC were enrolled. Differences in the incidence rate of radiation pneumonitis (RP) and progression-free survival (PFS) were assessed in patients with or without ILD of which CT showed non-usual interstitial pneumonia pattern between the durvalumab consolidation group and chemotherapy (combination of carboplatin and paclitaxel [CP]) consolidation group.ResultsThe incidence of RP was higher in patients with preexisting ILD (40% and 20% in the durvalumab and CP groups, respectively) than in those without ILD (26% and 8% in the durvalumab and CP groups, respectively). Univariate analysis showed that durvalumab therapy tended to increase the incidence of RP; however, preexisting ILD did not significantly increase the incidence of RP. The condition of all patients who developed RP improved with the administration of oral prednisolone. Among patients without ILD, the median PFS was 17 and 16 months in the durvalumab and CP groups, respectively. Among patients with preexisting ILD, median PFS was not achieved in the durvalumab group and was 8 months in the CP group.ConclusionsAlthough durvalumab consolidation therapy tended to increase the incidence of RP, it might be tolerable in stage III NSCLC patients with preexisting ILD.     

Correlation between eosinophil count,its genetic background and body mass index: The Nagahama Study

BackgroundObesity affects the pathogenesis of various chronic diseases, including asthma. Research on correlations between obesity/BMI and eosinophilic inflammation in asthma has yielded contradictory results, which could be partly ascribed to the absence of epidemiological data on the correlations. We aimed to elucidate the correlations between blood eosinophil count, its genetic backgrounds, and BMI in the general population.MethodsThis community-based Nagahama study in Japan enrolled 9789 inhabitants. We conducted self-reporting questionnaires, lung function tests, and blood tests in the baseline and 5-year follow-up studies. A genome-wide association study (GWAS) was performed in 4650 subjects at the baseline and in 4206 of these at the follow-up to determine single-nucleotide polymorphisms for elevated blood eosinophil counts. We assessed the correlations between BMI and eosinophil counts using a multifaceted approach, including the cluster analysis.ResultsEosinophil counts positively correlated with BMI, observed upon the interchange of an explanatory variable, except for subjects with the highest quartile of eosinophils (≥200/μL), in whom BMI negatively correlated with eosinophil counts. GWAS and human leukocyte antigen (HLA) imputation identified rs4713354 variant (MDC1 on chromosome 6p21) for elevated eosinophil counts, independent of BMI and IgE. Rs4713354 was accumulated in a cluster characterized by elevated eosinophil counts (mean, 498 ± 178/μL) but normal BMI.ConclusionsEpidemiologically, there may be a positive association between blood eosinophil counts and BMI in general, but there was a negative correlation in the population with high eosinophil counts. Factors other than BMI, particularly genetic backgrounds, may contribute to elevated eosinophil counts in such populations.     

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.     

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.     

Trunk muscle quality and quantity predict the development of metabolic syndrome and the increase in the number of its components in individuals without metabolic syndrome

Background and aimsThe metabolic syndrome has been reported by cross-sectional studies to have an association with skeletal muscle quality and quantity. Using a longitudinal study design, this study aimed to explicate the association between muscle characteristics assessed with computed tomography (CT) and the incidence and progression of metabolic syndrome.Methods and resultsIn this retrospective study on a cohort of employees undergoing annual physical examinations, we evaluated data from 554 participants without metabolic syndrome. The cross-sectional skeletal muscle area was determined based on CT data at the level of the third lumbar vertebra, and the skeletal muscle density (SMD) and skeletal muscle index (SMI) were measured. The participants were divided into four study groups according to the sex-specific median values for SMI and SMD. We followed the participants for a mean period of 3.1 years. In the sex- and age-adjusted model, SMI and SMD had an interaction effect on the longitudinal change in number of metabolic syndrome components (β = −0.074, p = 0.0727). Multiple regression analyses revealed that both low SMI and SMD was significantly associated with the change (β = 0.131, p = 0.0281), whereas the low SMI and high SMD, and high SMI and low SMD were not. Both low SMI and SMD (hazard ratio (HR), 2.42; 95% confidence interval, 1.28–4.78) showed an increased adjusted HR for incident metabolic syndrome.ConclusionThe participants with both low quality and quantity of skeletal muscles were associated with the incidence and progression of metabolic syndrome, whereas those with only low quantity or quality of skeletal muscles were not.     

Evolution of Myocardial Tissue Injury: A CMR Study Over a Decade After STEMI

BackgroundIn patients with a first ST-segment elevation myocardial infarction (STEMI), the multi-annual evolution of myocardial tissue injury parameters, as assessed by cardiac magnetic resonance (CMR), has not yet been described.ObjectivesThis study examined myocardial tissue injury dynamics over a decade after STEMI.MethodsSequential CMR examinations (within the first week after STEMI, and at 4, 12, months, and 9 years thereafter) were conducted in 74 patients with STEMI treated with primary percutaneous coronary intervention. Left ventricular function, infarct size (IS), and microvascular obstruction (MVO) were assessed at all time points. T21, T2, and T1 mapping (n = 59) were added at 9-year scan to evaluate the presence of iron and edema within the infarct core, respectively.ResultsIS decreased progressively and significantly between all CMR time points (all P < 0.001), with an average reduction rate of 5.8% per year (IQR: 3.5%-8.8%) and a relative reduction of 49% (IQR: 39%-76%) over a decade. MVO was present in 61% of patients at baseline, but was not present at the follow-up examinations. At 9-year CMR, 17 of 59 (29%) patients showed iron deposition within the infarct core, whereas 82% had persistent edema. Persistent iron and edema were associated with greater IS on any occasion (all P < 0.001), as well as the presence of MVO (P < 0.001). Patients with persistent iron and edema showed a lower relative regression of IS (P = 0.005 and P = 0.032, respectively) and greater end-systolic volumes over a decade (all P < 0.012 and P > 0.023, respectively). A T1 hypointense infarct core without evidence of T21 iron deposition (14 of 59 [24%] patients) was attributed to lipomatous metaplasia of the infarct.ConclusionsThe evolution of IS is a dynamic process that extends well beyond the first few months after STEMI. Persistence of iron and edema within the infarct core occurs up to a decade after STEMI and is associated with initial infarct severity and poor infarct healing.     

Clinical,radiological, and pathological features of anti-asparaginyl tRNA synthetase antibody-related interstitial lung disease

BackgroundMyositis and interstitial lung disease (ILD) frequently occur in patients with anti-aminoacyl-tRNA synthetase (ARS) antibodies. Nearly half of ARS-ILD patients have the acute or subacute form of the disease, and one-third of these patients show a deterioration in pulmonary function over the long-term course because of frequent recurrences and refractoriness to therapy. Several reports recently described different characteristics depending on the individual anti-ARS antibodies, and the anti-asparaginyl tRNA synthetase (KS) antibody was strongly linked to ILD rather than to myositis. We therefore hypothesized that KS-ILD may have clinical characteristics that differ from those of other ARS-ILDs. The aim of this study was to clarify the clinical, radiological, and pathological features of KS antibody-positive ILD.MethodsWe retrospectively analyzed 19 consecutive patients with KS-ILD who underwent initial clinical measurements and high-resolution computed tomography and pathological assessments. We also analyzed disease behavior based on pulmonary function test results during the follow-up period.ResultsOur KS-ILD cohort included patients with dermatomyositis (10.5%), primary Sjögren syndrome (5.3%), and idiopathic ILD (84.2%). Most patients presented with chronic onset (89.5%) and a nonspecific pattern of interstitial pneumonia at each radiological and pathological assessment (89.4% and 85.7%, respectively). The pulmonary function test results showed that the mean changes from the initial %forced vital capacity and %diffusing capacity of the lung for carbon monoxide at 3 years were 3.7% ± 2.9% and 9.35% ± 3.0%, respectively.ConclusionsMost KS-ILD patients showed a tendency for chronic disease onset and long-term stabilization of pulmonary function.     

Increased CD69 expression on activated eosinophils in eosinophilic chronic rhinosinusitis correlates with clinical findings

BackgroundEosinophilic chronic rhinosinusitis (ECRS) is a subtype of chronic rhinosinusitis associated with asthma. CD69 is an important marker of activation for eosinophils. But, whether a correlation exist between the CD69 expression on eosinophils and clinical findings is unclear.MethodsWe performed quantitative PCR and/or flow cytometry using tissue and purified eosinophils from the blood and nasal polyps of 12 patients with ECRS and from 8 patients without ECRS (controls). We assessed clinical findings including nasal polyp (NP) scores, sinus CT findings, and pulmonary function test results, and examined their possible association with the CD69 expression. We also performed CD69 cross-linking experiments in mouse eosinophils to investigate the functional role of CD69.ResultsLevels of cytokine mRNAs (IL-4, -5, -10, and -13) were significantly higher in purified NP eosinophils and tissues from patients with ECRS than the levels of those in controls. The expressions of major basic protein (MBP), eosinophilic cationic protein (ECP), eosinophilic-derived neurotoxin (EDN), eosinophil peroxidase (EPX) in cytotoxic granules, and CD69 mRNA were significantly higher in purified eosinophils from NPs than in those from blood. We also found a correlation between expression of CD69 and clinical findings. Moreover, we found EPX release from mouse eosinophils following CD69 cross-linking.ConclusionsThese data suggest that increased CD69 expression by eosinophils is not only a biomarker for nasal obstruction and pulmonary dysfunction, but also a potential therapeutic target for patients with ECRS and asthma.     

Wall Shear Stress Predicts Aortic Dilation in Patients With Bicuspid Aortic Valve

ObjectivesThis study sought to assess the predictive value of wall shear stress (WSS) for colocalized ascending aorta (AAo) growth rate (GR) in patients with bicuspid aortic valve (BAV).BackgroundBAV is associated with AAo dilation, but there is limited knowledge about possible predictors of aortic dilation in patients with BAV. An increased WSS has been related to aortic wall damage in patients with BAV, but no previous prospective study tested its predictive value for dilation rate. Recently, a registration-based technique for the semiautomatic mapping of aortic GR has been presented and validated.MethodsForty-seven patients with BAV free from valvular dysfunction prospectively underwent 4-dimensional flow cardiac magnetic resonance to compute WSS and subsequent follow-up with 2 electrocardiogram-gated high-resolution contrast-enhanced computed tomography angiograms for GR assessment.ResultsDuring a median follow-up duration of 43 months, mid AAo GR was 0.24 mm/year. WSS and its circumferential component showed statistically significant association with mid AAo GR in bivariate (P = 0.049 and P = 0.014, respectively) and in multivariate analysis corrected for stroke volume and either baseline AAo diameter (P = 0.046 and P = 0.014, respectively) or z-score (P = 0.036 and P = 0.012, respectively). GR mapping further detailed that GR was heterogeneous in the AAo and that circumferential WSS, but not WSS magnitude, showed statistically significant positive associations with GR in the regions with the fastest growth.Conclusions4D flow cardiac magnetic resonance–derived WSS and, in particular, its circumferential component predict progressive dilation of the ascending aorta in patients with BAV. Thus, the assessment of WSS may be considered in the follow-up of these patients.     

Lower dose of ethambutol may reduce ocular toxicity without radiological deterioration for Mycobacterium avium complex pulmonary disease

BackgroundEthambutol ocular toxicity is a major problem during combination chemotherapy for Mycobacterium avium complex (MAC) pulmonary disease (MAC-PD) due to years-long therapy for MAC.ObjectivesThis study aimed to identify the lower dose of daily ethambutol that can reduce ocular toxicity.MethodsWe retrospectively reviewed the medical records of 312 patients who visited The University of Tokyo Hospital between January 2007 and December 2017 for nontuberculous mycobacterial pulmonary disease. Seventy-six patients with MAC-PD who were treated with combination chemotherapy for the first time were analyzed in this study.ResultsEthambutol was discontinued because of visual symptoms in 13 patients (17%), 7 of whom were diagnosed with ethambutol ocular neuropathy. The dose per body weight was significantly higher in patients who developed ocular neuropathy than in those who did not (15.4 mg/kg/d vs. 12.5 mg/kg/d, respectively; p = 0.048). We assigned patients to higher or lower dose groups according to the median dose of 12.5 mg/kg/d. Although ocular neuropathy developed in 6 out of 38 patients in the higher dose group, ocular neuropathy developed in 1 out of 38 patients in the lower dose group (16% vs. 3%, respectively; p = 0.038). The failures of sputum culture conversion and radiological improvement were not significantly different between the two groups (p = 0.638 and 0.305, respectively). Macrolide resistance developed in one patient per group during follow-up (3% per group, p = 0.945).ConclusionsA lower dose of ethambutol may reduce ocular toxicity without radiological deterioration for pulmonary MAC infection.     

Positive association between body fat percentage and hyperuricemia in patients with hypertension: The China H-type hypertension registry study

Background and aimsThe relationship between the body fat percentage (BFP) and hyperuricemia is still unknown in different gender subjects. The purpose of this study was to determine the magnitude of the association between the BFP and the presence of hyperuricemia in the sex-specific group among hypertensive patients.Methods and resultsWe conducted a cross-sectional study enrolling 14,234 hypertensive participates from the Chinese Hypertension Registry Study. Body fat percentage (BFP) was calculated by simple anthropometric parameters. Hyperuricemia was defined as serum uric acid (SUA) level 420 umol/L in men and 360 umol/L in women. The mean BFP was 24.5% in men and 37.1% in women. Multiple logistic analyses showed that the relationship between BFP with the risk of hyperuricemia in a dose-dependent manner among both men (odds ratio [OR] 1.07, 95% CI 1.06, 1.09) and women (OR 1.08, 95% CI 1.06, 1.09) in the fully adjusted model. Subgroup analyses showed the positive association between BFP and the risk of hyperuricemia was consistent in all stratification subgroups (all P for interaction >0.05).ConclusionFor patients with hypertension, BFP was positively associated with an increased risk of hyperuricemia among both men and women.     

Interleukin-37 gene polymorphism and susceptibility to pulmonary tuberculosis among Iraqi patients

BackgroundControl of tuberculosis (TB) depends on a balance between host's immune factors and bacterial evasion strategies. Interleukin-37 (IL-37) is among the immunomodulatory factors that have been proposed to influence susceptibility to tuberculosis.MethodsA case–control study was conducted on 105 patients with pulmonary TB (37 active, 41 multi-drug resistant and 27 relapse) and 79 healthy controls to determine serum levels and single nucleotide polymorphisms (SNPs) of IL-37. The IL-37 level was assessed with an enzyme-linked immunosorbent kit, while DNA-sequencing was used to detect SNPs in the promoter region of IL37 gene.Results: Median level of IL-37 was markedly increased in serum of TB patients compared to controls (325.0 vs. 169.1 pg/mL; p < 0.001). This increase was universally determined in subgroups of patients distributed according to gender, age groups, and clinical type of disease, while no significant differences were found between the subgroups in patients or controls. Analysis of receiver operating characteristic curve confirmed these findings and IL-37 occupied a very good area under the curve, which was 0.816 (95% CI = 0.744–0.888; p < 0.001). At a cut-off value of 185.6 pg/mL, the sensitivity and specificity of IL-37 were 81.0 and 82.3%, respectively. Of the nine detected SNPs (rs2466449 G/A, rs2466450 A/G, rs2723168 G/A, rs3811042 G/A, rs3811045 T/C, rs3811046 G/T, rs3811047 A/G, rs3811048 G/A and rs200782323 G/A), only rs3811048 showed a significant association with TB; the G allele showed a significantly decreased frequency in TB patients compared to controls (25.2 vs. 44.9%; OR = 0.41; p < 0.001). It was possible to assign five haplotypes, and three showed significant differences between patients and controls. Frequency of haplotype A-A-G-A-C-T-G-A-G (0.331 vs. 0.213; OR = 2.10; p = 0.015) was significantly increased in TB patients compared to controls. On the contrary, frequencies of haplotypes A-A-G-A-C-T-G-G-G (0.029 vs. 0.116; OR = 0.24; p = 0.01) and A-A-G-G-T-G-A-G-G (0.140 vs. 0.275; OR = 0.45; p = 0.015) were significantly decreased in patients.ConclusionsIL-37 was up-regulated in the serum of TB patients irrespective of their gender, age or clinical type of disease. SNPs in the promoter region of IL37 gene were proposed to be associated with susceptibility to TB.     

Association between positivity of serum autoantibodies and liver disease severity in patients with biopsy-proven NAFLD

Background and aimsSome previous studies reported serum autoantibody positivity in patients with nonalcoholic fatty liver disease (NAFLD). The clinical significance of these findings remains uncertain. We aimed to investigate the association between the presence of serum autoantibodies and liver disease severity in NAFLD.Methods and resultsA total of 388 consecutive patients with biopsy-proven NAFLD were included in the study. Various serum autoantibodies (including also anti-nuclear antibodies [ANA]) were detected by indirect immunofluorescent or immunoblotting assays. Overall, 84 (21.6%) patients with biopsy-confirmed NAFLD had positivity for at least one of the measured serum autoantibodies. ANA positivity was present in 50 (12.9%) patients, whereas anti-U1RNP or pANCA antibodies were detectable in 9 (2.3%) and 6 (1.5%) patients, respectively. Multivariate logistic regression analysis showed that ANA positivity (adjusted-odds ratio: 4.51, 95%CI: 1.77–11.5; P = 0.002) or positivity of any serum autoantibodies (adjusted-odds ratio: 3.14, 95%CI: 1.30–7.62; P = 0.01) were independently associated with advanced liver fibrosis (stages F3–F4). In serum autoantibody/ANA-positive patients, the proportion of those with advanced fibrosis was also greater among carriers of PNPLA3 rs738409 GG or CG than among those carrying PNPLA3 rs738409 CC genotype.ConclusionsSerum autoantibody positivity was independently associated with advanced liver fibrosis in patients with biopsy-proven NAFLD. The presence of serum autoantibodies in patients with advanced fibrosis occurred more frequently amongst those carrying PNPLA3 rs738409 GG or CG genotypes.     

Mean platelet volume modifies the contribution of homocysteine to cardiovascular disease: A real-world study

Background and aimsThe effect of reductions in homocysteine (Hcy) on cardiovascular disease (CVD) was suggested to be modified by platelet activation, but the interaction between Hcy and platelet activation on CVD events is not well studied. Here, we aimed to examine the interaction between Hcy and platelet activation on CVD in a large, real-world population.Methods and resultsA total of 27,234 patients with hypertension (mean 63 years, 48% male) who were registered in Taicang city and free of CVD were prospectively followed up for new CVD events from 2017 to 2020. Hcy and platelet indices including mean platelet volume (MPV) were assayed at baseline. A total of 1063 CVD events were recorded during follow-up. Hcy at baseline was significantly associated with a higher risk of CVD (HR = 1.85, P < 0.001 for log-transformed Hcy). MPV showed a significant interaction effect with Hcy on CVD (HR = 1.20, P = 0.030 for the interaction term). The association between Hcy and CVD was significantly stronger in participants with a large (vs. small) MPV (HR = 2.71 vs. 1.32, P = 0.029 for log-transformed Hcy). For participants with both elevated Hcy and a large MPV, the attributable proportion of CVD events due to their interaction was 0.26 (95% CI: 0.06–0.45).ConclusionsThe association between Hcy and CVD was significantly stronger in patients with hypertension with a larger MPV. MPV may modify the contribution of Hcy to CVD events through synergistic interactions with Hcy. These findings suggest that MPV could be monitored and controlled in the prevention of CVD.     

Chest CT severity score and radiological patterns as predictors of disease severity,ICU admission,and viral positivity in COVID-19 patients

BackgroundChest computed tomography (CT) is a useful tool for the diagnosis of coronavirus disease-2019 (COVID-19), although its exact value for predicting critical illness remains unclear. This study evaluated the efficacy of chest CT to predict disease progression, pulmonary complications, and viral positivity duration.MethodsA single-center cohort study was conducted by consecutively including hospitalized patients with confirmed COVID-19. The chest CT patterns were described and a total severity score was calculated. The predictive accuracy of the severity score was evaluated using the receiver operating characteristic analysis, while a Cox proportional hazards regression model was implemented to identify the radiological features that are linked to prolonged duration of viral positivity.ResultsOverall, 42 patients were included with 10 of them requiring intensive care unit admission. The most common lesions were ground glass opacities (92.9%), consolidation (66.7%), and crazy-paving patterns (61.9%). The total severity score significantly correlated with inflammatory and respiratory distress markers, as well as with admission CURB-65 and PSI/PORT scores. It was estimated to predict critical illness with a sensitivity and specificity of 75% and 70%, respectively. Time-to-event analysis indicated that patients without ground-glass opacities presented significantly shorter median viral positivity (16 vs. 27 days).ConclusionsChest CT severity score positively correlates with markers of COVID-19 severity and presents promising efficacy in predicting critical illness. It is suggested that ground-glass opacities are linked to prolonged viral positivity. Further studies should confirm the efficacy of the severity score and elucidate the long-term pulmonary effects of COVID-19.     

Does a high intake of green leafy vegetables protect from NAFLD? Evidence from a large population study

Background and aimsResults of in vitro and in vivo studies showed that green leafy vegetables (GLV) could attenuate liver steatosis. However, little is known regarding the association between GLV intake and nonalcoholic fatty liver disease (NAFLD) in human. We examined the association of GLV intake with NAFLD in a large-scale adult population.Methods and resultsThis cross-sectional study investigated 26,891 adults in China who participated in health examinations from 2013 to 2017. Newly diagnosed NAFLD was detected by liver ultrasonography. Dietary intake was assessed by using a validated and standardized food frequency questionnaire. Multivariable logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) across categories of GLV intake. After adjustment for sociodemographic characteristics, lifestyle factors, and other dietary intakes, the OR (95% CI) for comparing the highest vs. lowest GLV intake categories (≥7 times/week vs. almost never) was 0.72 (0.59, 0.90) (P < 0.0001). In addition, a linear inverse association was demonstrated between GLV intake and NAFLD in women (P for trend = 0.04), but ORs for any intake category did not reach significance. Stratified analyses suggested a potential effect modification by obesity status; the ORs (95% CIs) for comparing the highest vs. lowest GLV intake categories was 0.72 (0.54, 0.97) in normal/overweight individuals and 1.04 (0.65, 1.65) in obese individuals (P-interaction < 0.0001).ConclusionThis large population-based study shows that high GLV intake is inversely associated with NAFLD, particularly in women and non-obese participants.     

Pathological and clinical relevance of selective recruitment of Langerhans cells in the respiratory bronchioles of smokers

BackgroundSmoking causes an influx of inflammatory cells including Langerhans cells (LCs) into the airways and lung parenchyma, thus inducing histological changes, such as emphysema and fibrosis. We examined the distribution and quantity of Langerhans cells in relation to clinical and pathological findings and explored the association between smoking and accumulation of Langerhans cells in the respiratory bronchioles.MethodsFifty-three patients who underwent lung resection for primary diseases, including lung cancer, were recruited. Histological and immunohistochemistry analyses were utilized to identify CD1a-positive Langerhans cells in peripheral lung specimens separated from primary lesions. Clinical characteristics, pathological changes, and distribution of CD1a-positive Langerhans cells distribution were assessed.ResultsOf the 53 patients, 35 were smokers and 18 were non-smokers. The number of Langerhans cells in the respiratory bronchioles was significantly increased in smokers as compared to that in non-smokers (p < 0.001). The number of Langerhans cells in smokers was significantly higher in patients with mild emphysema than in those without emphysema (p < 0.01). The high-LC group showed more frequent smoking-related histological changes, such as respiratory bronchiolitis, parenchymal fibrosis, accumulation of macrophages, and smoking-related interstitial fibrosis, than the low-LC group. However, there were no differences in the smoking indices and pulmonary functions of the groups.ConclusionsSelective accumulation of Langerhans cells in the respiratory bronchioles of smokers may lead to the development of smoking-related pathological changes.     

Decrease in hemoglobin level predicts increased risk for severe respiratory failure in COVID-19 patients with pneumonia

BackgroundIn December 2019, the coronavirus disease (COVID-19), caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), emerged in Wuhan, China, and has since spread throughout the world. This study aimed to investigate the association between the change in laboratory markers during the three days after pneumonia diagnosis and severe respiratory failure in COVID-19 patients.MethodsData of 23 COVID-19 patients with pneumonia, admitted to the Kumamoto City Hospital between February and April 2020 were retrospectively analyzed.ResultsAmong the 23 patients, eight patients received mechanical ventilation (MV) (MV group), and the remaining 15 comprised the non-MV group. The levels of hemoglobin (Hb) and albumin (Alb) decreased in the MV group during the three days after pneumonia diagnosis more than in the non-MV group (median Hb: 1.40 vs. ?0.10 g/dL, P = 0.015; median Alb: 0.85 vs. ?0.30 g/dL, P = 0.020). Univariate logistic regression analysis showed that the decrease in Hb was associated with receiving MV care (odds ratio: 0.313, 95% confidence interval: 0.100–0.976, P = 0.045). Receiver operating characteristic curve analyses showed that the optimal cut-off value for the decrease in Hb level was ?1.25 g/dL, with sensitivity and specificity values of 0.867 and 0.750, respectively.ConclusionsThe decrease in Hb level during the short period after pneumonia diagnosis might be a predictor of worsening pneumonia in COVID-19 patients.     

Monocyte to high-density lipoprotein ratio and cardiovascular events in patients on peritoneal dialysis

Background and aimsThe monocyte to high-density lipoprotein cholesterol ratio (MHR) is associated with multiple cardiovascular diseases. However, the role of the MHR in predicting cardiovascular diseases in patients on peritoneal dialysis remains unclear.Methods and resultsEight hundred and eighty incident peritoneal dialysis patients were enrolled from November 1, 2005, to February 28, 2017, and followed until May 31, 2017. Primary outcomes were cardiovascular events. Using the X-tile program, these patients were divided into three groups according to the MHR. Kaplan–Meier method and Cox regressions were used for survival analysis. During a median follow-up period of 26 months (interquartile range: 12–39 months), 139 cardiovascular events were recorded. After multiple adjustment, the high MHR group was associated with a 1.97-fold increase in the cardiovascular events hazard compared to that of the low group in the overall population (hazard ratio: 1.97; 95% CI, 1.19–3.28; P = 0.009). Subgroup analysis demonstrated that the association between the MHR and a higher risk of cardiovascular events was strongest in the subgroup of patients with diabetes (P for interaction = 0.004). In this subgroup, the high MHR group was found to be associated with a higher risk of cardiovascular events compared to the low group (hazard ratio: 7.69; 95% CI, 2.76–21.47).ConclusionThis study suggests that the MHR is independently associated with the risk of cardiovascular events in patients undergoing peritoneal dialysis, and diabetes status can influence the association between the MHR and the risk of cardiovascular events.     

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.