Recommendations and guidelines for the diagnosis and management of Coronavirus Disease-19 (COVID-19) associated bacterial and fungal infections in Taiwan.

Coronavirus disease-19 (COVID-19) is an emerging infectious disease caused by SARS-CoV-2 that has rapidly evolved into a pandemic to cause over 600 million infections and more than 6.6 million deaths up to Nov 25, 2022. COVID-19 carries a high mortality rate in severe cases. Co-infections and secondary infections with other micro-organisms, such as bacterial and fungus, further increases the mortality and complicates the diagnosis and management of COVID-19. The current guideline provides guidance to physicians for the management and treatment of patients with COVID-19 associated bacterial and fungal infections, including COVID-19 associated bacterial infections (CABI), pulmonary aspergillosis (CAPA), candidiasis (CAC) and mucormycosis (CAM). Recommendations were drafted by the 7th Guidelines Recommendations for Evidence-based Antimicrobial agents use Taiwan (GREAT) working group after review of the current evidence, using the grading of recommendations assessment, development, and evaluation (GRADE) methodology. A nationwide expert panel reviewed the recommendations in March 2022, and the guideline was endorsed by the Infectious Diseases Society of Taiwan (IDST). This guideline includes the epidemiology, diagnostic methods and treatment recommendations for COVID-19 associated infections. The aim of this guideline is to provide guidance to physicians who are involved in the medical care for patients with COVID-19 during the ongoing COVID-19 pandemic.

COVID-19 associated mold infections: Review of COVID-19 associated pulmonary aspergillosis and mucormycosis.

COVID-19-associated mold infection (CAMI) is defined as development of mold infections in COVID-19 patients. Co-pathogenesis of viral and fungal infections include the disruption of tissue barrier following SARS CoV-2 infection with the damage in the alveolar space, respiratory epithelium and endothelium injury and overwhelming inflammation and immune dysregulation during severe COVID-19. Other predisposing risk factors permissive to fungal infections during COVID-19 include the administration of immune modulators such as corticosteroids and IL-6 antagonist. COVID-19-associated pulmonary aspergillosis (CAPA) and COVID-19-associated mucormycosis (CAM) is increasingly reported during the COVID-19 pandemic. CAPA usually developed within the first month of COVID infection, and CAM frequently arose 10-15 days post diagnosis of COVID-19. Diagnosis is challenging and often indistinguishable during the cytokine storm in COVID-19, and several diagnostic criteria have been proposed. Development of CAPA and CAM is associated with a high mortality despiteappropriate anti-mold therapy. Both isavuconazole and amphotericin B can be used for treatment of CAPA and CAM; voriconazole is the primary agent for CAPA and posaconazole is an alternative for CAM. Aggressive surgery is recommended for CAM to improve patient survival. A high index of suspicion and timely and appropriate treatment is crucial to improve patient outcome.

STRESS granule-associated RNA-binding protein CAPRIN1 drives cancer progression and regulates treatment response in nasopharyngeal carcinoma.

Nasopharyngeal carcinoma (NPC) is a common malignancy of the head and neck that is mainly diagnosed in southern China and Southeast Asia, with a strong etiological link to Epstein‒Barr virus infection. Those with advanced-stage disease have a significantly worse prognosis. There is an urgent need to identify novel therapeutic targets for the recurrent or metastatic nasopharyngeal carcinoma. With a particular focus on Cell Cycle Associated Protein 1 (CAPRIN1), one of the important RNA-binding proteints associated with stress granule formation, we used RT‒qPCR and immunohistochemistry to validate CAPRIN1 expression in NPC tissues and cell lines. Further, CAPRIN1 expression was knocked down using siRNA, and the effect on cell proliferation and migration was systematically assessed by in vitro assays. As a result, we demonstrated that CAPRIN1 was elevated in NPC compared to adjacent normal tissues. Knockdown of CAPRIN1 in NPC cells inhibited proliferation and migration, involving the regulation of cell cycle protein CCND2 and EMT signaling, respectively. Notably, we found that CAPRIN1 knockdown promoted cell apoptosis by regulation of the expression of apoptosis-related proteins cleaved-PARP and cleaved-Caspase3. Knockdown of CAPRIN1 increased NPC cell sensitivity to rapamycin, and increased NPC cell sensitivity to cisplatin and to X-rays. In conclusion, CAPRIN1 might drive NPC proliferation, regulate cell cycle and apoptosis, and affect tumor cell response to anti-cancer agents and X-ray irradiation. CAPRIN1 might serve as a potential target for NPC.

Facile Synthesis of 3-Substituted Thiazolo[2,3-α]tetrahydroisoquinolines.

It was found that 4-hydroxy-2-butenoic ester (11) could not react with 3,4-dihydro-isoquinoline (4a). Individual addition reactions of γ-mercapto-α,ß-unsaturated esters (18) and -unsaturated amide (19) with 3,4-dihydroisoquinolines (4) were carried out under appropriate conditions to provide the corresponding thiazolo[2,3-α]isoquinoline derivatives with good yields (up to 87%) and significant diastereomeric selectivity. The mechanism of the crucial reaction was discussed.

Clinical features of tuberculosis and Bacillus Calmette-Guérin (BCG) -associated adverse effects in children: A 12-year study.

PURPOSE: To investigate the clinical feature of tuberculosis and BCG adverse effects in children and to examine whether delayed BCG vaccination changes the incidence of BCG osteomyelitis. METHODS: We analyzed patients younger than 18 years with tuberculosis or BCG-associated adverse effects from 2008 to 2019. We compared their clinical features, laboratory tests and outcomes. RESULTS: Totally 137 patients were collected, with 27% of pulmonary tuberculosis (PTB), 31% of extrapulmonary tuberculosis (EPTB) and 42% of BCG-associated adverse effects. The median age was older in PTB than EPTB group (17.1 vs 15.4 years; p = 0.015). More patients in EPTB group had fever than PTB group (55% vs 25%; p = 0.008). Compared with exclusively EPTB, more patients in EPTB plus PTB group had fever (78% vs 38%; p = 0.009), and had more systemic symptoms (67% vs 25%; p = 0.007), lower absolute lymphocyte count (1230 vs 1850/µL; p = 0.033), higher CRP level (5.62 vs 2.21 mg/dL; p = 0.024) and longer hospital stay (20 vs 11 days; p = 0.031). In BCG osteomyelitis group, the median time interval from vaccination to diagnosis was 16.4 months (IQR 15.0-20.2). Age at vaccination, either at birth or 5-8 month-old, did not affect the proportion of BCG osteomyelitis among children with BCG-associated adverse effects. CONCLUSION: Children with EPTB plus PTB had more fever, lower lymphocyte count and higher CRP. The median time interval from vaccination to diagnosis of BCG osteomyelitis was 16.4 months and the proportion of BCG osteomyelitis among children with BCG-associated adverse effects was not affected by delayed vaccination in this study.

Severe Mycoplasma pneumoniae pneumonia requiring intensive care in children, 2010-2019.

BACKGROUND/PURPOSE: Despite the high prevalence of Mycoplasma pneumoniae infections, reports on severe life-threatening M. pneumoniae pneumonia (MPP) in children are limited. METHODS: We retrospectively enrolled pediatric patients with PCR-positive MPP requiring ICU admission in a children's hospital in Taipei, Taiwan from Jun 2010 to October 2019. Clinical manifestations and laboratory data of severe MPP were analyzed. Macrolide susceptibility was determined by genotyping, and its relationship with clinical manifestations was also analyzed. RESULTS: Approximately 5% (34/658) children hospitalized for MPP required ICU admission. Compared with non-ICU cases (n = 291), ICU cases (n = 34) were associated with more underlying conditions, more pleural effusion, longer fever duration, longer hospital stay, the requirement of second-line antibiotic treatment, and delayed effective and second-line antibiotic treatment. Macrolide resistance was similar in ICU and non-ICU groups (53% vs 53%; p = 0.986). In severe MPP, patients requiring endotracheal intubation were associated with more septic shock, empyema, ARDS, prolonged fever after effective antibiotic treatment, delayed second-line and effective antibiotic treatment. In 18 of the 22 patients with pleural fluid analysis, the pleural effusion was alkaline (pH > 7.7) and lymphocyte-predominant. CONCLUSION: M. pneumoniae infection can cause severe life-threatening pneumonia in children. Delayed effective and second-line antibiotic treatments are associated with severe life-threatening MPP.

Clinical features and risk factors associated with bacteremia of nontyphoidal salmonellosis in pediatric patients, 2010-2018.

BACKGROUND/PURPOSE(S): This study aimed to investigate clinical features and antimicrobial susceptibility of inpatient children with nontyphoidal salmonellosis from 2010 to 2018. METHODS: We retrospectively collected pediatric patients with nontyphoidal Salmonella infection confirmed by positive cultures in a tertiary medical center in Taiwan from 2010 to 2018. Patients' characteristics, clinical manifestations, and laboratory data were collected. Serogroup category and antimicrobial susceptibility were also analyzed. RESULTS: Of total 569 isolates, ampicillin resistant rate was 53% in average, third-generation cephalosporin resistant rate was 6.7%, ciprofloxacin resistant rate was 9% and trimethoprim-sulfamethoxazole resistant rate was 30%. Compared to the resistant rates in 2010, the resistance rate of third generation cephalosporin was significantly higher (3.4% vs. 11%, p = 0.003) but that of ciprofloxacin was significantly lower (20% vs. 11%, p < 0.001) in 2018. Among 297 inpatients with nontyphoidal salmonellosis, Group D (38%) was the most common in the bacteremia patients whereas Group B (48%) was the most common in the non-bacteremia patients. Among 244 immunocompetent inpatients with community-acquired salmonellosis, the bacteremia patients had significantly longer fever duration and diarrhea duration before hospitalization (p < 0.001), and significant higher rate of anemia (p = 0.028) due to either thalassemia trait or prolonged disease course than the non-bacteremia patients. CONCLUSION: Third-generation cephalosporin was still the drug of choice for nontyphoidal Salmonella infection in children though the resistant rate increased progressively. Significant risk factors associated with bacteremia were longer fever and diarrhea duration and anemia due to either thalassemia trait or prolonged disease course in immunocompetent children.

Dengzhan Shengmai capsules and their active component scutellarin prevent cognitive decline in APP/PS1 mice by accelerating Aß aggregation and reducing oligomers formation.

There is currently no effective treatment to prevent the progress of Alzheimer's disease (AD). The traditional Chinese herbs Dengzhan Shengmai (DZSM) capsules and their active component scutellarin possess multiple effects and are clinically used for the treatment of cerebrovascular diseases. Scutellarin has been reported to affect Aß aggregation. However, the effects of DZSM capsules on AD remain unknown. Through in vivo experiments, our study proved that the alleviating effects of DZSM capsules on cognitive deficits of AD mice were due to the role of scutellarin, which up-regulated low toxic amyloid plaques and down-regulated highly toxic soluble Aß42 and Aß40 levels in cortex. In vitro, we confirmed scutellarin's role in accelerating transforming Aß42 monomers into high-molecular-mass aggregates by biochemical assays, which supported the results observed in drug-treated APP/PS1 mice. In detail, the 1:10 ratio of scutellarin/Aß42 mixtures promoted production of large ß-sheet-rich fibrils whereas the 1:1 ratio promoted production of protofibrils. In addition, the binding between scutellarin and Aß monomers was quantified by microscale thermophoresis test and the apparent dissociation constant (Kd) was 1284.4 ±â€¯238.8 µM. What's more, binding regions between scutellarin and Aß fibrils were predicted by computational docking models and scutellarin might bind parallel to the long axis of Aß42 fibrils targeting hydrophobic grooves at residues 35-36 or 39. In conclusion, DZSM capsules protected against cognitive defects of AD through scutellarin-mediated acceleration of Aß aggregation into fibrils or protofibrils and reduction of soluble Aß oligomers, thus suggesting potential clinical applications of DZSM capsules and scutellarin in the treatment of AD.

Dioscin attenuates oxLDL uptake and the inflammatory reaction of dendritic cells under high glucose conditions by blocking p38 MAPK.

Dioscin has been shown to affect the regulation of metabolic diseases, including diabetes; however, the mechanism of action is still unclear. Under high glucose (HG) conditions, the expression of scavenger receptors and the uptake of oxidized low­density lipoprotein (oxLDL) are upregulated in dendritic cells (DCs), which are critical steps in atherogenesis and inflammation. In this study, the focus was on the impact of dioscin on the function of DCs. Immature DCs were cultured with: 5.5 mM glucose medium (control group); 30 mM glucose medium (HG group); HG + 10 mM dioscin; HG + 20 mM dioscin; HG + 30 mM dioscin; and HG + 40 mM dioscin. For subsequent experiments, 30 mM dioscin was used as the experimental concentration. Dichlorodihydrofluorescein fluorescence was used to measure the intracellular production of reactive oxygen species (ROS) in DCs. The expression levels of the scavenger receptors, including class A scavenger receptors (SR­A), CD36 and lectin­like oxidized low­density lipoprotein receptor­1 (LOX­1) were determined via quantitative PCR. The protein expression of p38 mitogen­activated protein kinase (MAPK) was determined by western blotting. Furthermore, ELISA was used to detect the levels of interleukin (IL)­6, IL­10 and IL­12. Finally, DCs were incubated with diOlistic (Dil)­labeled oxLDL, and flow cytometry analysis was used to investigate the Dil­oxLDL­incorporated fraction. The incubation of DCs with dioscin inhibited the induction of ROS production, in a dose­dependent manner, under HG conditions. The upregulation of SR­A, CD36 and LOX­1 genes was partially abolished by dioscin, which also partially reversed p38 MAPK protein upregulation. Furthermore, increased secretion of IL­6 and IL­12, and decreased secretion of IL­10 in DCs, induced by HG, was also reversed by dioscin. To conclude, dioscin could attenuate the production of ROS, inflammatory cytokine secretion and oxLDL uptake by DCs in HG conditions by preventing the expression of scavenger receptors and p38 MAPK, thus playing a positive role in preventing atherogenesis.

MicroRNA-18a promotes cancer progression through SMG1 suppression and mTOR pathway activation in nasopharyngeal carcinoma.

miR-18a has been reported to be upregulated in nasopharyngeal carcinoma (NPC) tissues by microarray assays. However, the roles and the underlying mechanisms of miR-18a in NPC remain poorly understood. Here we demonstrated by real-time RT-PCR that miR-18a expression is upregulated in NPC tissues, and positively correlated with tumor size and TNM stage. Moreover, miR-18a expression could be upregulated by NF-κB activation or Epstein-Barr virus encoded latent membrane protein 1 expression. The ectopic expression of miR-18a promoted NPC cell proliferation, migration and invasion, while the repression of miR-18a had opposite effects. Candidate genes under regulation by miR-18a were screened out through a whole-genome microarray assay, further identified by a reporter assay and verified in clinical samples. SMG1, a member of the phosphoinositide 3-kinase-related kinases family and an mTOR antagonist, was identified as functional target of miR-18a. Our results confirmed that miR-18a exerts its oncogenic role through suppression of SMG1 and activation of mTOR pathway in NPC cells. Importantly, in vivo xenograft tumor growth in nude mice was effectively inhibited by intratumor injection of miR-18a antagomir. Our data support an oncogenic role of miR-18a through a novel miR-18a/SMG1/mTOR axis and suggest that the antitumor effects of antagomir-18a may make it suitable for NPC therapy.

Identification of RRAS gene related to nasopharyngeal carcinoma based on pathway and network-based analyses.

BACKGROUND: Nasopharyngeal carcinoma (NPC) is a highly aggressive neoplasm mainly distributed in the eastern and southeastern parts of Asia. NPC has a poor prognosis among head and neck cancers, and molecular-targeted therapies showed limited clinical efficacy. METHODS: We reviewed publications in the PubMed database and extracted genes associated with NPC. The online tool WebGestalt was used to perform Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis for these genes. Next, the two parameters, Jaccard Coefficient (JC) and Overlap Coefficient (OC), were used to analyze the crosstalk of each pair of selected pathways. The new NPC-related genes were predicted by protein-protein interaction (PPI) network combined with hub genes extraction. Western blotting, qRT-PCR, and immunohistochemistry (IHC) were used to detect the expression of candidate genes in NPC cells and tissues, and cellular function assays were used to explore the effects of genes on NPC cells. RESULTS: A total of 552 genes were identified and used to build an NPC-related gene set (NPCgset). Pathways enriched in KEGG pathway analysis were further used for crosstalk analysis and were grouped into two modules: one was related to the carcinogenesis process, and the other was correlated with the immune response. Eight genes from the NPCgset were selected to build a PPI network, and two hub genes PIK3CA and AKT1 were chosen. Proteins interacting with PIK3CA were analyzed; among them, the expression of RRAS was down-regulated in NPC and associated with poor prognosis of NPC patients. Furthermore, RRAS suppressed proliferation, invasion and the epithelial-mesenchymal transformation (EMT) of the HK1 and 5-8F cell lines. CONCLUSIONS: Our study may help to explore the biological processes underlying NPCgset and suggests that RRAS may act as a tumor suppressor gene in NPC.

Total Synthesis of (+)-Antrocin and Its Diastereomer and Clarification of the Absolute Stereochemistry of (-)-Antrocin.

Using 2,2-dimethyl cyclohexanone as the starting compound, (+)-antrocin and its diastereomer have been synthesized. The absolute stereochemistry of (-)-antrocin, a natural sesqui-terpenoid and an antagonist in some types of cancer cells, was clarified using the character data of (+)-antrocin. The synthetic procedure involved two key steps: (1) the reaction of vinyl magnesium bromide with 2,2-dimethyl-6-t-butyl-dimethyl-silyoxy-methyl-1-cyclo-hexanone to give a vinyl cyclohexanol derivative and (2) a highly stereoselective intramolecular Diels-Alder (IMDA) reaction of the camphanate-containing triene intermediate. The relative energy levels of the possible transition states of the IMDA reaction of the camphanate-containing triene were obtained from density functional theory calculations, proving the stereospecific formation of the target molecule.

Inhibition of pentraxin 3 in glioma cells impairs proliferation and invasion in vitro and in vivo.

Pentraxin 3 (PTX3) is an inflammatory molecule that is involved in immune responses, inflammation, and cancer. Recent evidence suggests that PTX3 plays a critical role in tumor progression; however, its impact on the biological function of gliomas remains unknown. In the present study, immunohistochemical staining showed that patients with high-grade gliomas exhibited increased expression levels of PTX3 compared to those with low-grade gliomas (P < 0.001). Furthermore, knockdown of PTX3 in GBM8401 cells inhibits proliferation, increases p21 protein levels, and decreases cyclin D1 protein levels, resulting in cell cycle arrest at the G0/G1 phase. In addition, knockdown of PTX3 significantly decreases GBM8401 cell migration and invasion through the downregulation of matrix metalloproteinase-1 and -2 (MMP-1 and MMP-2) expression. In a GBM8401 xenograft animal model, PTX3 knockdown decreases tumor growth in vivo. In conclusion, PTX3 plays an important role in glioma cell proliferation and invasion, and may thus serve as a novel potential therapeutic target in the treatment of gliomas.

Correlation of ovalbumin of egg white components with allergic diseases in children.

BACKGROUND: Immunoglobulin E (IgE)-mediated food allergy, such as egg white allergy, is common in young children (<3 years old), but not all young children sensitive to egg white present with allergic symptoms. This study investigated the relationship between sensitization to egg white component allergens and clinical manifestations of allergic diseases in young children. METHODS: From March to December 2010, 2256 children with physician-diagnosed allergic diseases were tested for serum levels of egg white, ovalbumin, and ovomucoid-specific IgE in the Pediatric Allergy and Asthma Center of Chang Gung Memorial Hospital. Serum was analyzed for specific IgE antibodies to egg white, ovalbumin, and ovomucoid by ImmunoCAP (Phadia, Uppsala, Sweden). Allergen-specific IgE levels ≥0.35 kUA/L were defined as positive. RESULTS: There was a significantly higher sensitization rate to egg white and its components in children aged 2-4 years old. The sensitization rate to egg white, ovalbumin, and ovomucoid in this age group was 53.5%, 48.3%, and 37.2%, respectively, and the trend of the sensitization decreased with age (p < 0.001). After adjusting for age, sensitization to egg white and ovalbumin was associated with children with dermatitis [egg white: odds ratio (OR) = 1.28, 95% confidence intervals (CI) = 1.03-1.58, p < 0.05; ovalbumin: OR = 1.30, 95% CI = 1.04-1.62, p < 0.05]. Children with ovomucoid sensitization had no statistically significant risk among different groups in the current study. CONCLUSION: Children aged 2-4 years old have higher sensitivity to egg white, ovalbumin, and ovomucoid. Children with egg white and ovalbumin sensitization have a higher risk for atopic dermatitis, and ovalbumin has a more important contribution. Furthermore, we suggested that in children with atopic dermatitis, if they are aged 2-4 years old and are having egg white and ovalbumin sensitization, avoiding eating raw or slightly heated eggs might have a beneficial effect.

End Stage Renal Disease as a Potential Risk Factor for Retinal Vein Occlusion.

End stage renal disease (ESRD) has been reported to be an important risk factor for systemic vascular disease. Retinal vein occlusion (RVO) is closely related with cardiovascular diseases; however, its association with ESRD had not been reported. The aim of the study was to investigate whether ESRD is a risk factor for RVO, including central retinal vein occlusion (CRVO) and branch retinal vein occlusion (BRVO). This population-based study is based on the longitudinal data from Taiwan National Health Insurance Research Database. The study cohort comprised 5344 patients with diagnosis of ESRD on hemodialysis or peritoneal dialysis during the period from January 1996 to December 2011. For each ESRD patient, we selected 20 non-ESRD patients matched on age and sex. Each ESRD patient and his/her controls were followed from the initiation of renal dialysis until either the diagnosis of RVO or censorship. Kaplan-Meier method was used to compare the hazard of RVO between cohorts. Stratified Cox proportional hazard models were applied to estimate the hazard ratio (HR) adjusted by the comorbidities of RVO including diabetes mellitus (DM), hypertension, hypercholesteremia, and hypertriglyceridemia. After stratifying by DM status, the statistics were applied again to examine the associations among the DM cohort and non-DM cohort.The 16-year RVO cumulative incidence for ESRD cohort was 2-fold to the non-ESRD (1.01% vs 0.46%). After matching with age, sex, hypertension, and hypercholesteremia, the adjusted HR was 1.46 (95% confidence interval = 1.07-2.01, P value = 0.018). By further excluding patients with DM, the adjusted HR escalated to 2.43 (95% confidence interval = 1.54-3.83, P < 0.001). In contrast, there was no significant risk of ESRD on RVO in the DM patients (HR = 1.03). We conclude that among the non-DM patients, ESRD cases had significantly higher RVO rate than the non-ESRD, which indicates that ESRD maybe a potential risk factor for the development of RVO in nondiabetic patients.

Pyromellitic dithioimides: thionation improves air-stability and electron mobility of N-type organic field-effect transistors.

Thionation and fluorination of pyromellitic diimides (PyDIs) increased the electron mobility and on/off ratio of the original diimides by two orders of magnitude and improved the threshold voltage and air-stability of diimide compounds.

Linear oligoarylamines: electrochemical, EPR, and computational studies of their oxidative states.

A series of straight-chain oligoarylamines were synthesized and examined by electrochemical, spectroelectrochemical, electron paramagnetic resonance techniques, and density functional theory (DFT) calculation. Depending on their electrochemical characteristics, these oligoarylamines were classified into two groups: one containing an odd number and the other an even number of redox centers. In the systems with odd redox centers (N1, N3, and N5), each oxidation was associated with the loss of one electron. As for the systems with even redox centers (N2, N4, and N6), oxidation occurred by taking N2 as a unit. Absorption spectra of linear oligoarylamines at various oxidative states were obtained to investigate their charge transfer behaviors. Moreover, DFT-computed isotropic hyperfine coupling constants and spin density were in accordance with the EPR experiment, and gave a close examination of oligoarylamines at charged states.

High altitude-induced borderline pulmonary hypertension impaired cardiorespiratory fitness in healthy young men.

OBJECTIVE: High altitude exposure has been suggested to cause borderline elevation of pulmonary artery pressure (PAP) in quite a few healthy individuals. This cohort study was to investigate the impact of altitude induced borderline pulmonary hypertension (PH) on cardiorespiratory fitness in healthy subjects. METHODS: 299 healthy Chinese young men with normal PAP were consecutively studied between July 2011 and September 2013. Among these subjects 114 kept living at low altitude (450m), 91 ascended to high altitude (3700m) from low altitude within 24h (acute exposure), and 94 resided at 3700m for more than 1year (chronic exposure). Mean PAP and cardiac function were examined by echocardiography, and cardiorespiratory fitness was determined by predicted work capacity at a heart rate of 170beats per minute (PWC170). RESULTS: Mean PAP remained within normal range (<20mmHg) in 113 of 114 participants (99%) at low altitude. In contrast, the incidence of borderline PH (mPAP between 20 and 25mmHg) was 29% and 37% for respective acute and chronic exposures. Compared to the subjects with normal mPAP within each of the exposure groups, the subjects with borderline PH had increased right ventricular Tei index (RV-Tei), which correlated with the decline of PWC170 (acute exposure: r=-0.296, p=0.004; chronic exposure: r=-0.247, p=0.016). However, these changes were relatively milder than those with confirmed PH (mPAP>25mmHg). CONCLUSION: Borderline PH compromised cardiorespiratory fitness in healthy young men. The decline of cardiorespiratory fitness was related at least in part with the impaired right ventricular function, which was correlated with the elevated mPAP.

Nonapnea sleep disorders and incident chronic kidney disease: a population-based retrospective cohort study.

Nonapnea sleep disorders (NASDs) are associated with an increased risk of stroke, diabetes, and hypertension. No longitudinal study has yet examined the association between NASD and chronic kidney disease (CKD) by using epidemiologic study methods. To test this hypothesis, we examined the effect of NASD on the incidence of CKD in a large population-based retrospective cohort study. Based on a retrospective cohort study of a general population sample of 128 to 436 patients in the Taiwan National Health Insurance Research Database from January 1, 1998 to December 31, 2001, 42 to 812 NASD patients were followed up for 10.2 ±â€Š3.12 years, and additional 85 to 624 individuals had no NASD at baseline. The International Classification of Diseases, Ninth Revision, Clinical Modification was used to identify the diagnosis of disease. Cox proportional hazard regression models were used to assess the association between NASD and subsequent CKD risk. The incidence rate of CKD was significantly higher in the NASD cohort than in the comparison cohort (2.68 vs 1.88 per 1000 person-years, respectively). After we adjusted for age, sex, and comorbidities, the risk of developing CKD was significant for patients with NASD (adjusted hazard ratio [HR] = 1.13; 95% confidence interval [CI] = 1.05-1.22; P < 0.01). Among different types of NASDs, patients with sleep disturbance associated disorders had a 14% increased risk of developing CKD (95% CI = 1.03-1.26; P < 0.01), whereas patients with insomnia had a 13% increased risk of subsequent CKD (95% CI = 1.02-1.25; P < 0.05) compared with the non-NASD cohort. Kaplan-Meier survival analysis indicated that the CKD-free rate was 1% lower in the NASD cohort than in the comparison cohort (log-rank test, P < 0.0001). Our study provides evidence that patients with NASD have an increased risk of developing subsequent CKD compared with patients without NASD; men, elderly people, and patients with concomitant comorbidities are at the greatest risk.