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ObjectiveIn individuals with epiglottitis, chronic obstructive pulmonary disease (COPD) is a common comorbidity; however, the impact of COPD under such circumstances is not well documented. Therefore, we performed this population-based study to determine whether, in adults, COPD is a risk factor for epiglottitis.MethodsIn this retrospective matched-cohort study, data obtained from the Taiwan National Health Insurance Research Database were analyzed. We identified all patients newly diagnosed as having COPD in 2000-2011 and performed frequency matching and propensity-score matching for every patient with COPD individually to another patient without a COPD diagnosis. We used epiglottitis occurrence as the study endpoint, and we investigated the hazard ratio of epiglottitis by using the Cox proportional hazards model after adjustment for potential confounders.ResultsIn the frequency matching, the cumulative epiglottitis incidence was significantly higher (p = 0.005) in the COPD cohort. According to the adjusted Cox proportional hazard model, COPD exhibited a significant association with elevated epiglottitis incidence (adjusted hazard ratio: 1.76; 95% confidence interval: 1.15-2.70, p = 0.009). Similar trend was observed in the propensity-score matching analysis (adjusted hazard ratio: 1.50; 95% confidence interval: 0.99-2.29, p = 0.057). Our subgroup analysis revealed COPD to be an epiglottitis risk factor in male patients and those aged 40-64 years.ConclusionsThis is the first nationwide matched-cohort research to examine the association of COPD with epiglottitis. Our results revealed that COPD may be a potential risk factor for epiglottitis; thus, clinicians should be mindful of the potential increased risk of epiglottitis following COPD.

OBJECTIVE:Studies have revealed that 3.5%-26.6% of patients with epiglottitis have comorbid diabetes mellitus (DM). However, whether preexisting DM is a risk factor for acute epiglottitis remains unclear. In this study, our aim was to explore the relationship between preexisting DM and acute epiglottitis in different age and sex groups by using population-based data in Taiwan. METHODS:We analyzed data between January 2000 and December 2013 obtained from the Taiwan National Health Insurance Research Database. The case group consisted of 2,393 patients with acute epiglottitis. The control group comprised 9,572 individuals without epiglottitis, frequency matched by sex, age, urbanization level, and income. Underlying DM was retrospectively assessed in the cases and controls. Univariate and multivariate logistic regression analyses were used to investigate the associations between underlying DM and acute epiglottitis. RESULTS:Of the 2,393 patients, 180 (7.5%) had preexisting DM, whereas only 530 (5.5%) of the 9,572 controls had preexisting DM. Multivariate logistic regression analyses indicated that preexisting DM was significantly associated with acute epiglottitis (adjusted odds ratio [aOR] = 1.42, 95% confidence interval [CI] = 1.15-1.75, P = 0.004). Subgroup analysis showed that the association between DM and epiglottitis remained significant for men (aOR = 1.57, 95% CI: 1.19-2.08, p = 0.002) but not for women. Age-stratified analysis revealed a significant association between DM and acute epiglottitis in patients aged 35-64 years. Use of anti-diabetic agents was not significantly associated with the development of acute epiglottitis among diabetic patients, including oral hypoglycemic agents (OHA) alone (aOR = 0.88, 95% CI = 0.53-1.46, p = 0.616), and OHA combined with insulin/ insulin alone (aOR = 1.30, 95% CI = 0.76-2.22, p = 0.339). The association between presence of diabetes complications and the occurrence of acute epiglottitis was also not significant among diabetic patients in this study setting (aOR = 0.86, 95% CI = 0.59-1.26, p = 0.439). CONCLUSIONS:The results of our large-scale population-based case-control study indicate that preexisting DM is one of the possible factors associated with the development of acute epiglottitis. Physicians should pay attention to the symptoms and signs of acute epiglottitis in DM patients, particularly in men aged 35-64 years.

Background: Cellular senescence is a specialized form of growth arrest that is generally irreversible. Upregulated p16, p53, and p21 expression and silencing of E2F target genes have been characterized to promote the establishment of senescence. It can be further aided by the transcriptional repression of proliferation-associated genes by the action of HP1γ, HMGA, and DNMT proteins to produce a repressive chromatin environment. Therefore, senescence has been suggested to functions as a natural brake for tumor development and plays a critical role in tumor suppression and aging. Methodology/Principal Findings: An in vitro senescence model has been established by using K562 cells treated with 50 nM doxorubicin (DOX). Since p53 and p16 are homozygously deleted in the K562 cells, the DOX-induced senescence in K562 cells ought to be independent of p53 and p16-pRb pathways. Indeed, no change in the expression of the typical senescence-associated premalignant cell markers in the DOX-induced senescent K562 cells was found. MicroRNA profiling revealed upregulated miR-375 in DOX-induced senescent K562 cells. Treatment with miR-375 inhibitor was able to reverse the proliferation ability suppressed by DOX (p<0.05) and overexpression of miR-375 suppressed the normal proliferation of K562 cells. Upregulated miR-375 expression was associated with downregulated expression of 14-3-3zeta and SP1 genes. Autophagy was also investigated since DOX treatment was able to induce cells entering senescence and eventually lead to cell death. Among the 24 human autophagy-related genes examined, a 12-fold increase of ATG9B at day 4 and a 20-fold increase of ATG18 at day 2 after DOX treatment were noted. Conclusions/Significance: This study has demonstrated that in the absence of p53 and p16, the induction of senescence by DOX was associated with upregulation of miR-375 and autophagy initiation. The anti-proliferative function of miR-375 is possibly exerted, at least in part, by targeting 14-3-3zeta and SP1 genes. [ABSTRACT FROM AUTHOR]

[This corrects the article DOI: 10.1371/journal.pone.0251455.].

Atherosclerosis is the main cause of cardiac and peripheral vessel infarction in developed countries. Recent studies have established that gut microbiota and their metabolites play important roles in the development and progression of cardiovascular disease; however, the underlying mechanisms remain unclear. The present study aimed to investigate endothelium plaque lesion formation in ApoE-deficient rats fed a normal chow diet under germ-free (GF) and specific-pathogen-free (SPF) conditions at various time points. There was no difference in serum cholesterol and triglyceride levels between SPF-rats and GF-rats. Histological studies revealed that the GF-rats developed endothelium plaques in the aorta from 26 to 52 weeks, but this was not observed in SPF-rats. GF-rat coronary arteries had moderate-to-severe endothelium lesions during this time period, but SPF-rat coronary arteries had only mild lesion formation. Immunohistochemical staining showed higher accumulation of CD68-positive and arginase-negative foamy-like macrophages on the arterial walls of GF-rats, and expression of TNF-α and IL-6 in foam cells was only observed in GF-rats. In addition, microbial metabolites, including equol derivatives, enterolactone derivatives, indole-3-propionate, indole-3-acrylic acid, cholic acid, hippuric acid, and isoquinolone, were significantly higher in the SPF group than in the GF group. In conclusion, our results indicate that gut microbiota may attenuate atherosclerosis development.

Background/aimsUndetectable HCV RNA 12 weeks after the end of treatment (SVR12) has been the valid efficacy endpoint in the era of direct-acting antivirals (DAAs). Its concordance with SVR4 and SVR24 and long-term durability is unknown in Taiwanese chronic hepatitis C (CHC) patients.MethodsA total of 1080 CHC patients who received all-oral DAAs and an achieved end-of-treatment virological response (EOTVR), defined as undetectable HCV RNA at the end of therapy, were consecutively enrolled. HCV RNA was monitored 4, 12, and 24 weeks after EOT. Patients who achieved SVR24, defined as undetectable HCV RNA 24 weeks after EOT, were followed annually for assessing SVR durability.ResultsEleven (1.02%) patients experienced HCV RNA reappearance after EOT. The most frequent timing of RNA reappearance was observed at SVR4 (n = 7), followed by SVR12 (n = 3) and SVR 24 (n = 1). The positive predictive value (PPV) and negative predictive value (NPV) of SVR4 in predicting SVR12 were 99.7% and 100%, respectively, whereas the PPV and NPV of SVR12 in predicting SVR24 were 99.9% and 100%, respectively. Pyrosequencing confirmed delayed relapse rather than reinfection for the patient who had detectable HCV RNA at SVR24. Among 978 patients who achieved SVR24, after a median follow-up period of 17.3±8.2 months, the SVR durability is 100% up to a 4-year follow-up.ConclusionAchievement of SVR12 provides excellent durability of HCV seroclearance after DAA therapy. On-demand HCV RNA beyond SVR12 should be recommended for patients with unexplainable abnormal liver function or high-risk behaviors.

BackgroundA typical assessment for sarcopenia involves the use of abdominal computed tomography (CT) for calculating the skeletal muscle index (SMI) at the level of the third lumbar vertebra (L3). However, abdominal CT is not regularly performed on patients with head and neck cancer (HNC). We investigated whether masticatory SMI (M-SMI) measurements based on head and neck CT scans can be used to conduct sarcopenia assessments by evaluating whether M-SMI is correlated with L3-SMI.MethodsAbdominal and head and neck CT images of patients with trauma (n = 50) and HNC (n = 52) were analyzed retrospectively. Both manual delineation and threshold selection methods were used to measure cross-sectional areas of masticatory muscles and those of muscles at the L3 level on CT images. Muscle cross-sectional areas were normalized to height squared to calculate SMI, and a multivariate linear regression model was established to evaluate the correlation between the M-SMI and L3-SMI. Receiver operating characteristic curve analysis was used to assess the ability of the M-SMI to identify sarcopenia, and Cox logistic regression was used to identify predictors of sarcopenia.ResultsPatients with HNC had significantly lower M-SMI and L3-SMI than did patients with trauma (p = 0.011 and 0.03, respectively). M-SMI and L3-SMI were strongly correlated (r = 0.901, p < 0.001); in the multivariate model that included sex, the correlation was stronger (r = 0.913, p < 0.001). The associations of sarcopenia with a lower M-SMI (p < 0.001), male sex (p = 0.028), and advanced age (p = 0.011) were significant, and multivariate logistic analysis demonstrated that an M-SMI of ConclusionsM-SMI assessment in routine head and neck CT scans is feasible and can be an alternative for detecting sarcopenia in patients with HNC.

BACKGROUND:The mortality rate of patients on extracorporeal membrane oxygenation (ECMO), especially those patients that develop acute kidney injury (AKI) is high. Acute kidney disease (AKD) is a term used to describe the continuum from AKI to chronic kidney disease. However, the role of AKD in predicting the prognosis of patients on ECMO support is unclear. METHODS:A total of 168 patients who received ECMO support and survived for more than 7 days at a single hospital from 2003 to 2008 were enrolled for this study and followed up for 10 years or till mortality. Kaplan-Meier analysis and Cox proportional hazards model were used to determine the prognostic factors associated with survival. RESULTS:The median survival times of patients with stage 0, stage 1, stage 2 and stage 3 AKD were ≥ 10 years, 43.9 months, 1 month, and half a month, respectively. There were statistically significant differences in cumulative survival rate between patients with stage 3 AKD and those with stage 0, 1, and 2 AKD (Cox-Mantel log rank test, p

Daily urine protein (UP) loss is a cumbersome but important measurement to guide diagnosis and treatment of renal disease. Spot urine protein-creatinine ratio (UPCR) can been applied to estimate daily proteinuria. However, the correlations between spot and 24h proteinuria remain controversial. In this cross-sectional study, simultaneous collection of 24h and spot urines were performed from 1,039 (derivation cohort) and 204 CKD patients (validation cohort) of Chang Gung Memorial Hospital, from 2007 to 2017. The correlations between spot UPCR and 24h proteinuria were compared. The mean age of patients of derivation and validation cohort was 63 and 55 years and the mean estimated glomerular filtration rate was 62 ± 35 and 59 ± 36 mL/min/m2, respectively. The correlation coefficient was 0.819 between UPCR and 24hUP. Prediction equation was derived as: Log1024hUP (g) = 0.814 x Log10UPCR (mg/mg) + 0.110 x Gender- 0.004 x Age + 0.004 x Body weight (kg) + 0.002 x CKD stage coefficient- 0.018, where CKD stage coefficient: CKD stage G1 = 1, G2 = 2, G3a = 3.1, G3b = 3.2, G4 = 4, G5 = 5. Correlation coefficient between measured and predicted 24hUP among derivation group and validation group is 0.866 and 0.915, respectively. However, the agreement of spot and daily estimates was less pronounced with proteinuria > 3g than lower values in Bland-Altman analysis. Spot UPCR can accurately predict 24hUP in patients with daily proteinuria below 3g. The development of this equation may facilitate estimation of 24hUP in the clinical practice.

ObjectiveWhether dysrhythmia is a risk factor of sudden sensorineural hearing loss (SSNHL) remains unclear. In this study, we aimed to investigate the risk of developing SSNHL among patients with dysrhythmia in different age and gender groups by using population-based data in Taiwan.MethodsWe conducted a matched cohort study by analyzing data between January 2000 and December 2013 obtained from the Taiwan National Health Insurance Research Database. 41,842 newly diagnosed dysrhythmia patients and 83,684 comparison subjects without dysrhythmia were selected from claims. The incidence of sudden sensorineural hearing loss at the end of 2013 was determined in both groups. Univariate and multivariate logistic regression analyses were used to investigate the risk of SSNHL among patients with dysrhythmia.ResultsThe incidence of SSNHL was 1.30-fold higher in the dysrhythmia group compared with the control group (53.2 versus 40.9 per 100,000 person-years), and using Cox proportional hazard regressions, the adjusted hazard ratio (HR) was 1.40 (95% confidence interval [CI], 1.15-1.70). Gender-stratified analysis revealed a significantly higher risk of SSNHL in patients with dysrhythmia than in those without dysrhythmia for both men and women (HR = 1.34, 95% CI = 1.02-1.76, P = 0.039, HR = 1.35, 95% CI = 1.02-1.78, P = 0.035, respectively). Age-stratified analysis revealed remarkable associations between dysrhythmia and SSNHL among those aged less than 40 years and more than 65 years (HR = 2.18, 95% CI = 1.03-4.64, P = 0.043 and HR = 1.54, 95% CI = 1.14-2.09, P = 0.006, respectively).ConclusionsOur findings support dysrhythmia as an independent risk factor for SSNHL. Based on the study results, clinicians managing patients with dysrhythmia should be aware of the increased risk of developing SSNHL, especially among patients aged 65 years, and counsel patients to seek medical advice immediately if they experience any acute change in their hearing ability.

ObjectiveThis study aims to investigate the association of serum vitamin D (VD) levels with the severity of liver fibrosis (LF) in post Kasai's portoenterostomy biliary atresia (PKBA) patients living with their native liver.MethodsIn this cross-sectional study, carried out in a tertiary Children's Hospital in Taipei, Taiwan, PKBA patients living with their native liver were enrolled. Liver biochemistry data, serum 25-hydroxyvitamin D (25-OHVD), acoustic radiation force impulse (ARFI), and scores of Pediatric Quality of Life questionnaire (PedsQL) were collected.ResultsAll the enrolled 33 PKBA patients (36.4% males), aged 1-23 years, possessed 25-OHVD less than 30ng/ml. An inverse correlation was detected between serum 25-OHVD and ARFI (r2 = 0.175; p = 0.024). We selected a cutoff value of 23ng/mL to divide PKBA patients into two groups, as the p-value was the most significant at this point when comparing the median ARFI of two groups (p = 0.003). Ten (30.3%) had 25-OHVD≥23ng/ml (HVD group), whereas 23(69.7%) had 25-OHVDConclusionVD levels are inversely associated with severity of LF in PKBA patients with native liver.

BACKGROUND:Technique failure secondary to peritonitis is a grave impediment to remain in peritoneal dialysis (PD) therapy leading to high mortality. Multidisciplinary predialysis education (MPE) has shown improvement in outcomes of chronic kidney disease (CKD) patients. However, the legacy effects of MPE in PD patients remain unclear. METHODS:All patients who started PD at single hospital in 2007-16 were enrolled. The incidences of peritonitis and peritonitis-related mortality were compared between MPE recipients and non-recipients. The content of the MPE was standardized in accordance with the NKF/DOQI guidelines. Kaplan-Meier analysis and Cox proportional hazards model were applied to identify the prognostic factors associated with peritonitis-free survival. RESULTS:Of 398 PD patients, 169 patients had received MPE before starting PD. The patients of MPE group had a lower peritonitis rate [median (IQR) 0 (0.29) versus 0.11 (0.69) episodes/person-year, P< 0.001] and a lower percentage of peritonitis-related deaths (3.6% versus 8.7%, P = 0.04) compared with the non-MPE group. The median time to the first episode of peritonitis in the non-MPE and MPE groups was 33.9 months and 46.7 months, respectively (Cox-Mantel log rank test, P = 0.003). Cox regression analysis revealed that MPE assignment (HR: 0.594; 95% CI: 0.434-0.813, P< 0.001) were significant independent predictors for peritonitis-free survival. CONCLUSIONS:An efficient standardized MPE program may prolong the time to the first episode of peritonitis and reduce peritonitis rate, independent of age, gender, diabetes, hypertension, educational status and PD modality. Subsequently, decreased peritonitis-related death.

White-nose syndrome (WNS) caused by the pathogenic fungus Pseudogymnoascus destructans is decimating the populations of several hibernating North American bat species. Little is known about the molecular interplay between pathogen and host in this disease. Fluorescence microscopy ambient ionization mass spectrometry was used to generate metabolic profiles from the wings of both healthy and diseased bats of the genus Myotis. Fungal siderophores, molecules that scavenge iron from the environment, were detected on the wings of bats with WNS, but not on healthy bats. This work is among the first examples in which microbial molecules are directly detected from an infected host and highlights the ability of atmospheric ionization methodologies to provide direct molecular insight into infection.

Simultaneous second primary tumors (SSPT) are not uncommon in patients with oral cavity squamous cell carcinoma (OSCC) living in areas where the habit of betel quid chewing is widespread. We sought to identify the main prognostic factors in OSCC patients with SSPT and incorporate them into a risk stratification scheme.A total of 1822 consecutive patients with primary OSCC treated between January 1996 and February 2014 were analyzed for the presence of SSPT. The 18-month and 5-year overall survival (OS) rates served as the main outcome measures.Of the 1822 patients, 77 (4%) were found to have SSPT (i.e, two malignancies identified within one month of each other). The 18-month and 5-year OS rates in patients without SSPT and with SSPT were 82% and 69%, and 72% and 53%, respectively (p = 0.0063). Patients with SSPT were further divided into patients with either esophageal cancer or hepatocellular carcinoma (eso-HCC subgroup, n = 8) and other tumors (NO eso-HCC subgroup, n = 69). After multivariate analysis, neck nodal extracapsular spread (ECS, n = 18) and the presence of eso-HCC were identified as independent adverse prognostic factors. The 18-month OS rates of SSPT patients with both eso-HCC and ECS (n = 5) vs. the remaining patients (n = 72) were 0% and 78%, respectively (p < 0.0001).OSCC patients with neck nodal ECS and esophageal cancer or hepatocellular carcinoma as SSPT have a dismal short-term prognosis.

OBJECTIVES: The aim of this cohort study was to examine the role of the chemokine (C-X-C motif) ligand 9 (CXCL9) on nasopharyngeal carcinoma (NPC). MATERIALS & METHODS: Sera from 205 NPC patients and 231 healthy individuals, and 86 NPC tumor samples were enrolled. CXCL9 expression in tissue samples was analyzed by quantitative real-time PCR and immunohistochemistry. CXCL9 serum concentrations were measured by enzyme-linked immunosorbent assay. RESULTS: CXCL9 expression was significantly higher in tumors than in normal epithelium. CXCL9 serum concentrations were also significantly higher in NPC patients compared to those in healthy individuals (516.8±617.6 vs. 170.7±375.0 pg/mL, P290 pg/mL, median) before treatment had worse prognoses for overall survival and disease-free survival (P = 0.045 and P = 0.008, respectively). Multivariate logistic regression analyses also indicated that higher CXCL9 serum levels were an independent prognostic factor for disease-free survival (P = 0.015). CONCLUSION: Our study demonstrated that CXCL9 is associated with tumor burden and aggressiveness of NPC tumors and the serum level of this ligand may be useful as a prognostic indicator.