Independent risk factor of drug eruption in immune checkpoint inhibitors treated liver cancer patients: high systemic immune-inflammation index.

PURPOSE: The clinical application of immune checkpoint inhibitors (ICIs) has significantly improved the prognosis of liver cancer patients. However, drug eruption associated with ICI monotherapy or combination therapy not only impacts the quality of life and treatment progress of liver cancer patients but also poses a potential threat to their lives. The study aims to investigate the risk factors of drug eruption in liver cancer patients undergoing ICIs in real-world settings. METHODS: We retrospectively collected data from liver cancer patients who underwent ICI therapies at the Third Affiliated Hospital of Sun Yat-sen University between 2021 and 2022. A propensity score matching (PSM) method was employed to match 31 liver cancer patients with ICI-related drug eruption (drug eruption group) to 228 liver cancer patients without immune-related adverse reactions (control group) in a 1:2 ratio, creating two groups of patients with comparable baseline characteristics. Subsequently, logistic regression analysis was then conducted to analyze the clinical risk factors associated with drug eruption caused by ICIs. RESULTS: Before PSM, there were statistically significant differences between the drug eruption group (31 cases) and the control group (228 cases) in two variables: Child-Pugh liver function classification and presence of vascular invasion (both p < 0.05). However, after PSM, no statistically significant differences were found in the clinical variables between the drug eruption group (28 cases) and the control group (52 cases). Univariate analysis revealed significantly higher levels of aspartate amino-transferase, alanine aminotransferase, glutamyl transpeptidase, and systemic immune-inflammation index (SII) and a significantly lower rate of liver cancer resection surgery before immunotherapy in liver cancer patients with drug eruption compared to the control group (p < 0.05). Multivariate analysis indicated that an elevated SII level before immunotherapy was significantly associated with the occurrence of drug eruption in liver cancer patients treated with ICIs (p < 0.05). The predictive performance of SII before immunotherapy in liver cancer patients for ICI-related drug eruption yielded an area under the receiver operator characteristic curve of 0.852, with a critical value of 749.189. Sensitivity and specificity were determined as 85.7% and 75%, respectively (p < 0.05). CONCLUSIONS: Elevated systemic immune-inflammation index is identified as a risk factor for drug eruption occurrence in liver cancer patients treated with ICI therapies.

Gut microbiota modulates COPD pathogenesis: role of anti-inflammatory Parabacteroides goldsteinii lipopolysaccharide.

OBJECTIVE: Chronic obstructive pulmonary disease (COPD) is a global disease characterised by chronic obstruction of lung airflow interfering with normal breathing. Although the microbiota of respiratory tract is established to be associated with COPD, the causality of gut microbiota in COPD development is not yet established. We aimed to address the connection between gut microbiota composition and lung COPD development, and characterise bacteria and their derived active components for COPD amelioration. DESIGN: A murine cigarette smoking (CS)-based model of COPD and strategies evaluating causal effects of microbiota were performed. Gut microbiota structure was analysed, followed by isolation of target bacterium. Single cell RNA sequencing, together with sera metabolomics analyses were performed to identify host responsive molecules. Bacteria derived active component was isolated, followed by functional assays. RESULTS: Gut microbiota composition significantly affects CS-induced COPD development, and faecal microbiota transplantation restores COPD pathogenesis. A commensal bacterium Parabacteroides goldsteinii was isolated and shown to ameliorate COPD. Reduction of intestinal inflammation and enhancement of cellular mitochondrial and ribosomal activities in colon, systematic restoration of aberrant host amino acids metabolism in sera, and inhibition of lung inflammations act as the important COPD ameliorative mechanisms. Besides, the lipopolysaccharide derived from P. goldsteinii is anti-inflammatory, and significantly ameliorates COPD by acting as an antagonist of toll-like receptor 4 signalling pathway. CONCLUSION: The gut microbiota-lung COPD axis was connected. A potentially benefial bacterial strain and its functional component may be developed and used as alternative agents for COPD prevention or treatment.

Self-reported mental health status of pregnant women in Sweden during the COVID-19 pandemic: a cross-sectional survey.

BACKGROUND: The COVID-19 pandemic has contributed to unprecedented worries and challenges for pregnant women due to social restrictions and changes in maternity care provision. We aimed to investigate the mental health impact of COVID-19 pandemic on pregnant women in Sweden and explore factors associated with poor perinatal mental health in this specific context. METHOD: This was a nation-wide cross-sectional survey of pregnant women living in Sweden. Validated questionnaires were distributed through non-profit organizations´ websites and social media channels from May 2020 to February 2021. Perinatal depression, anxiety, and acute stress reaction were assessed using the Edinburgh Postnatal Depression Scale (EPDS), Generalized Anxiety Disorder-7 (GAD-7) and Impact Event Scale (Revised) (IES-R), respectively. Sociodemographic characteristics and self-perceived mental well-being were also obtained. Factors associated with mental health outcomes were analyzed using multivariate logistic regression model. RESULTS: Among a total of 470 participants, 43.2% (n = 203) reported depression (EPDS ≥13), 25.7% (n = 121) moderate to severe anxiety (GAD-7 score ≥ 10), and 23.7% (n = 110) moderate to severe acute stress reaction (IES-R ≥ 33). 27.4% participants (n = 129) expressed concerns regarding their mental well-being during the pandemic. Pregnant mothers who had sick family members reported poorer mental health outcomes than those who did not (median [Interquartile range (IQR)] EPDS scores: 14.0 [8.75-18.0] vs 11.0 [6.25-15.0], p < .001; median (IQR) GAD7 scores: 7.0 [4.0-12.25] vs 6.0 [3.0-9.0], p = .003); median (IQR) IES-R scores: 20.0 [9.0-38.0] vs 15.0 [7.0-30.0], p = .048). Logistic regression analyses revealed that risk factors for poor mental health outcomes were having a sick family member with any illness, unemployment, and experiencing a substantially stressful life event. Having a higher educational level and a younger age during the pandemic were protective. CONCLUSION: Depression and anxiety were highly prevalent among pregnant women in Sweden during the COVID-19 pandemic, indicating a need for professional mental health support for this vulnerable group of population. Unemployment was an associated risk factor whereas younger age and higher educational level were protective suggesting an important role of socio-economic factors in modulating the impact of COVID-19 pandemic on perinatal mental health.

Revealing the effects of molecular orientations on the azo-coupling reaction of nitro compounds driven by surface plasmonic resonances.

A recent report on the azo coupling of 4-nitrobenzo-15-crown-ether (4NB15C) and 4-nitrothiophenol (4NTP) indicated that the reaction barrier could be reduced greatly with surface plasmonic effects on silver dendritic nanostructures in aqueous solution. Accordingly, an azo coupling reaction mechanism was proposed based on one or two SERS peaks. Toward a profound understanding of this azo coupling reaction mechanism, it is crucial to scrutinize the origin of the full SERS spectrum. Here, we construct a molecular model consisting of 4NTP and 4NB15C on an Ag7 cluster that simulates a silver dendritic nanostructure, and investigate the SERS spectra of the azo coupling of these two molecules. We propose five different adsorption sites and 13 different orientations of 4NTP on the Ag7 cluster and optimize the geometries of the five configurations. With each optimized configuration of 4NTP adsorbed on Ag7, we further consider the azo coupling product with a 4NB15C molecule and simulate the corresponding Raman spectra. Comparing the measured Raman spectra and model analysis, we conclude that the azo coupling reaction depends decisively on a parallel molecular orientation of the adsorbed 4NTP relative to the facets of Ag7, the orientation of which further directs the subsequent reaction for the product of 4NB15C-4NTP.

Artificial neural networks improve LDCT lung cancer screening: a comparative validation study.

BACKGROUND: This study proposes a prediction model for the automatic assessment of lung cancer risk based on an artificial neural network (ANN) with a data-driven approach to the low-dose computed tomography (LDCT) standardized structure report. METHODS: This comparative validation study analysed a prospective cohort from Chiayi Chang Gung Memorial Hospital, Taiwan. In total, 836 asymptomatic patients who had undergone LDCT scans between February 2017 and August 2018 were included, comprising 27 lung cancer cases and 809 controls. A derivation cohort of 602 participants (19 lung cancer cases and 583 controls) was collected to construct the ANN prediction model. A comparative validation of the ANN and Lung-RADS was conducted with a prospective cohort of 234 participants (8 lung cancer cases and 226 controls). The areas under the curves (AUCs) of the receiver operating characteristic (ROC) curves were used to compare the prediction models. RESULTS: At the cut-off of category 3, the Lung-RADS had a sensitivity of 12.5%, specificity of 96.0%, positive predictive value of 10.0%, and negative predictive value of 96.9%. At its optimal cut-off value, the ANN had a sensitivity of 75.0%, specificity of 85.0%, positive predictive value of 15.0%, and negative predictive value of 99.0%. The area under the ROC curve was 0.764 for the Lung-RADS and 0.873 for the ANN (P = 0.01). The two most important predictors used by the ANN for predicting lung cancer were the documented sizes of partially solid nodules and ground-glass nodules. CONCLUSIONS: Compared to the Lung-RADS, the ANN provided better sensitivity for the detection of lung cancer in an Asian population. In addition, the ANN provided a more refined discriminative ability than the Lung-RADS for lung cancer risk stratification with population-specific demographic characteristics. When lung nodules are detected and documented in a standardized structured report, ANNs may better provide important insights for lung cancer prediction than conventional rule-based criteria.

Improved appropriateness of anti-tuberculosis prescription by the expert prescription review program in Taiwan.

BACKGROUND: A nationwide program initiated by Taiwan CDC was conducted by the Taiwan Society of Tuberculosis and Lung Disease to improve the appropriateness of anti-TB prescriptions in Taiwan. METHODS: All anti-TB prescriptions from 12 hospitals across Taiwan were reviewed by experienced pulmonologists, according to the 2011 Taiwan TB treatment guidelines, between May and October 2013. The investigation period was divided into three stages: May to June, July to August, and September to October. The concordance rates between anti-TB prescriptions and the guidelines were compared among the three stages and between medical centers and regional hospitals. RESULTS: A total of 2574 new anti-TB prescriptions were reviewed. The appropriateness of anti-TB prescriptions was 82.0%. The most dominant error was inappropriate dosage of anti-TB medications. The appropriateness improved significantly with prescription review, and the concordance rates were 78.7%, 80.6%, and 87.6% in stages 1, 2, and 3, respectively (P < 0.001). The inappropriateness of medication dosage also improved significantly, with the rates of inappropriate dosage dropping from 10.2% in stage 1-5.4% in stage 3 (Odds ratio 0.491, P < 0.001). The appropriateness rates showed no significant difference between regional hospitals and medical centers (82.5% vs. 81.3%, Odds ratio 0.915, P = 0.393), but the improvement of prescription appropriateness was significant in regional hospitals but not in medical centers. CONCLUSION: Prescription review by TB experts is an effective approach to improve the appropriateness of anti-TB prescriptions.

Virtual Screening and In Vitro Evaluation of PD-1 Dimer Stabilizers for Uncoupling PD-1/PD-L1 Interaction from Natural Products.

Genetic mutations accumulated overtime could generate many growth and survival advantages for cancer cells, but these mutations also mark cancer cells as targets to be eliminated by the immune system. To evade immune surveillance, cancer cells adopted different intrinsic molecules to suppress immune response. PD-L1 is frequently overexpressed in many cancer cells, and its engagement with PD-1 on T cells diminishes the extent of cytotoxicity from the immune system. To resume immunity for fighting cancer, several therapeutic antibodies disrupting the PD-1/PD-L1 interaction have been introduced in clinical practice. However, their immunogenicity, low tissue penetrance, and high production costs rendered these antibodies beneficial to only a limited number of patients. PD-L1 dimer formation shields the interaction interface for PD-1 binding; hence, screening for small molecule compounds stabilizing the PD-L1 dimer may make immune therapy more effective and widely affordable. In the current study, 111 candidates were selected from over 180,000 natural compound structures through virtual screening, contact fingerprint analysis, and pharmacological property prediction. Twenty-two representative candidates were further evaluated in vitro. Two compounds were found capable of inhibiting the PD-1/PD-L1 interaction and promoting PD-L1 dimer formation. Further structure optimization and clinical development of these lead inhibitors will eventually lead to more effective and affordable immunotherapeutic drugs for cancer patients.

Meta-analysis of genome-wide association studies identifies multiple lung cancer susceptibility loci in never-smoking Asian women.

Genome-wide association studies (GWAS) of lung cancer in Asian never-smoking women have previously identified six susceptibility loci associated with lung cancer risk. To further discover new susceptibility loci, we imputed data from four GWAS of Asian non-smoking female lung cancer (6877 cases and 6277 controls) using the 1000 Genomes Project (Phase 1 Release 3) data as the reference and genotyped additional samples (5878 cases and 7046 controls) for possible replication. In our meta-analysis, three new loci achieved genome-wide significance, marked by single nucleotide polymorphism (SNP) rs7741164 at 6p21.1 (per-allele odds ratio (OR) = 1.17; P = 5.8 × 10(-13)), rs72658409 at 9p21.3 (per-allele OR = 0.77; P = 1.41 × 10(-10)) and rs11610143 at 12q13.13 (per-allele OR = 0.89; P = 4.96 × 10(-9)). These findings identified new genetic susceptibility alleles for lung cancer in never-smoking women in Asia and merit follow-up to understand their biological underpinnings.

Accuracy of Presurgical Functional MR Imaging for Language Mapping of Brain Tumors: A Systematic Review and Meta-Analysis.

Purpose To compare functional magnetic resonance (MR) imaging for language mapping (hereafter, language functional MR imaging) with direct cortical stimulation (DCS) in patients with brain tumors and to assess factors associated with its accuracy. Materials and Methods PubMed/MEDLINE and related databases were searched for research articles published between January 2000 and September 2016. Findings were pooled by using bivariate random-effects and hierarchic summary receiver operating characteristic curve models. Meta-regression and subgroup analyses were performed to evaluate whether publication year, functional MR imaging paradigm, magnetic field strength, statistical threshold, and analysis software affected classification accuracy. Results Ten articles with a total of 214 patients were included in the analysis. On a per-patient basis, the pooled sensitivity and specificity of functional MR imaging was 44% (95% confidence interval [CI]: 14%, 78%) and 80% (95% CI: 54%, 93%), respectively. On a per-tag basis (ie, each DCS stimulation site or "tag" was considered a separate data point across all patients), the pooled sensitivity and specificity were 67% (95% CI: 51%, 80%) and 55% (95% CI: 25%, 82%), respectively. The per-tag analysis showed significantly higher sensitivity for studies with shorter functional MR imaging session times (P = .03) and relaxed statistical threshold (P = .05). Significantly higher specificity was found when expressive language task (P = .02), longer functional MR imaging session times (P < .01), visual presentation of stimuli (P = .04), and stringent statistical threshold (P = .01) were used. Conclusion Results of this study showed moderate accuracy of language functional MR imaging when compared with intraoperative DCS, and the included studies displayed significant methodologic heterogeneity. © RSNA, 2017 Online supplemental material is available for this article.

Multi-layer silicon nitride-on-silicon polarization-independent grating couplers.

A polarization-independent grating coupler is proposed and demonstrated in a 3-layer silicon nitride-on-silicon photonic platform. Polarization independent coupling was made possible by the supermodes and added degrees of geometric freedom unique to the 3-layer photonic platform. The grating was designed via optimization algorithms, and the simulated peak coupling efficiency was -2.1 dB with a 1 dB polarization dependent loss (PDL) bandwidth of 69 nm. The fabricated grating couplers had a peak coupling efficiency of -4.8 dB with 1 dB PDL bandwidth of over 100 nm.

Size distribution of salbutamol/ipratropium aerosols produced by different nebulizers in the absence and presence of heat and humidification.

BACKGROUND: Few studies have evaluated the size distribution of inhaled and exhaled aerosolized drugs, or the effect of heated humidification on particle size and lung deposition. The present study evaluated these aspects of bronchodilator (salbutamol/ipratropium) delivery using a lung model in the absence and presence of heat and humidification. METHODS: We positioned filters to collect and measure the initial drug, inhaled drug, and exhaled drug. Particle size distribution was evaluated using an 8-stage Marple personal cascade impactor with 0.2-µm polycarbonate filters. RESULTS: A greater inhaled drug mass was delivered using a vibrating mesh nebulizer (VMN) than by using a small volume nebulizer (SVN), when heated humidifiers were not employed. When heated and humidified medical gas was used, there was no significant difference between the inhaled drug mass delivered by the VMN and that delivered by the SVN. A significantly greater mass of inhaled 1.55-µm drug particles was produced by the VMN than with the SVN, under heated and humidified conditions. However, the mass median aerodynamic diameters (MMADs) of the aerosolized drug produced by the SVN and VMN did not differ significantly under the same conditions. CONCLUSIONS: The VMN produced more fine particles of salbutamol/ipratropium, and the drug particle size clearly increased in the presence of heat and humidification.

Peroral Endoscopic Myotomy in Children With Achalasia: A Relatively Long-term Single-center Study.

BACKGROUND: Achalasia is a disease caused by neuromuscular dysfunction in the esophagogastric junction, with a relatively low incidence among children. Peroral endoscopic myotomy (POEM) is a new endoscopic procedure for the treatment of achalasia; however, it is rarely applied in children. OBJECTIVES: We aim to study the feasibility, safety, and effectiveness of POEM as a treatment for pediatric achalasia. METHODS: A total of 21 pediatric patients (ages from 11 months to 18 years) diagnosed as having achalasia and treated with POEM from October of 2014 to October of 2016 in our hospital were included in our study. Indices such as clinical manifestations, nutritional status, Eckardt scores, high-resolution esophageal manometric measurements, gastroduodenoscopic findings, and upper gastroenterographic findings after treatment were respectively compared with those before treatment to analyze the effectiveness and safety of POEM. RESULTS: All of the 21 children successfully received POEM. The patients were followed up for duration ranged from 3 to 24 months. Among these children, symptoms such as vomiting and dysphagia were significantly alleviated or resolved. The Eckardt scores had an average drop of 7 points after treatment compared with those before treatment. Postoperative gastroduodenoscopy and upper gastroenterography showed that the opening of the cardiac orifice was significantly enlarged and obstruction at the lower esophagus was significantly relieved. CONCLUSIONS: POEM is a mini-invasive technique and a promising new treatment for pediatric patients, making it worthy of further clinical research and application.

Genetic Modifiers of Progression-Free Survival in Never-Smoking Lung Adenocarcinoma Patients Treated with First-Line Tyrosine Kinase Inhibitors.

RATIONALE: Patients with non-small cell lung cancer (NSCLC) with mutated epidermal growth factor receptor (EGFR) are relatively sensitive to EGFR-tyrosine kinase inhibitor (TKI) treatment and have longer progression-free survival (PFS) when treated with EGFR-TKI compared with platinum-based chemotherapy. However, many patients with advanced NSCLC who have mutated EGFR do not respond to first-line EGFR-TKI treatment and still have shorter PFS. OBJECTIVES: The aim of this study was to identify genetic variants associated with PFS among patients with lung adenocarcinoma who were treated with first-line EGFR-TKIs. METHODS: A genome-wide association study on PFS was performed in never-smoking women diagnosed with lung adenocarcinoma and who were treated with first-line EGFR-TKIs (n = 128). Significant single-nucleotide polymorphisms (SNPs) were selected for follow-up association analysis (n = 198) and for replication assay in another independent cohort (n = 153). MEASUREMENTS AND MAIN RESULTS: We identified SNPs at 4q12 associated with PFS at genome-wide significance (P < 10-8) and with an estimated hazard ratio of more than 4. This association was also replicated in a larger but similar cohort and in an independent NSCLC cohort. Follow-up functional analyses showed that these SNPs were associated with the expression of EGFR, which encodes the TKI target, and with a nearby gene neuromedin-U, which encodes a G protein-coupled receptor ligand known to be involved in the progression of NSCLC. Considering these as possible prognostic biomarkers for the treatment of patients with late-stage lung cancer, we found that these SNPs were not associated with EGFR mutation status or with polymorphism of the Bcl2-interacting mediator of cell death gene. CONCLUSIONS: Genetic variants in 4q12 merit further investigation to assess their potential as pharmacogenomic predictors for and to understand the biology underlying its influence on PFS in patients treated with TKI therapy.

Comparative efficacy and tolerability of beclomethasone/formoterol and fluticasone/salmeterol fixed combination in Taiwanese asthmatic patients.

BACKGROUND: The study was designed to compare the efficacy and tolerability of a fixed combination of extra-fine beclomethasone and formoterol, with the fixed combination fluticasone and salmeterol in Taiwanese asthmatic patients. METHODS: This was a phase III, multicentre, randomized, two-arm parallel groups, controlled study. Patients with moderate to severe asthma were randomized to a 12-week treatment with either beclomethasone 100 mcg plus formoterol 6 mcg (BDP/F) or fluticasone 125 mcg plus salmeterol 25 mcg (FP/S), both delivered 2 inhalations twice daily. The efficacy and tolerability of these two combinations were compared. RESULTS: Among the 253 randomized subjects, 244 patients were evaluable (119 in the BDP/F group and 125 in the FP/S group). A significant improvement from baseline to the end of treatment period was observed in both BDP/F and FP/S groups in forced expiratory volume in the first second (FEV1), forced vital capacity (FVC), morning and evening peak expiratory flow (PEF), Asthma Control Test (ACT) score and the use of rescue medication. FVC increase from pre-dose was significant after 5 min post inhalation in the BDP/F group only, while statistically significant within group improvement was not achieved until 30 min post inhalation in the FP/S group. CONCLUSION: The BDP/F combination is comparable in efficacy and tolerability to FP/S combination in Taiwanese asthmatic patients, with the advantage of rapid onset of improvement of FVC, consistent with the faster improvement of pulmonary hyperinflation with BDP/F.

Pay attention to treating a subgroup of positional obstructive sleep apnea patients.

BACKGROUND/PURPOSE: Positional obstructive sleep apnea (OSA) is defined as an apnea hypopnea index at least twice as high in the supine position as in the lateral position. Whether a positional OSA patient persistently has positional OSA in the follow-up period is unknown. This study was conducted to investigate the maintenance of the positional effect on OSA patients and the predictors of changing from positional OSA to nonpositional OSA. METHODS: Patients who were diagnosed to have positional OSA were screened for a follow-up polysomnography (PSG), which evaluated the effect of the same lateral position as baseline PSG on the severity of OSA. Those who met the criteria of positional OSA in both PSGs were classified as the unchanged group, the others were classified as the changed group. RESULTS: Seventy-eight positional OSA patients were enrolled in the final analyses. Twenty-seven of the enrolled patients (35%) were changed to nonpositional OSA patients in the second PSG. A higher apnea index in the lateral position was found in the changed group compared with that in the unchanged group (p = 0.02). Logistic regression also showed that the apnea index in the lateral position was the only independent predictor of changing from positional OSA to nonpositional OSA in the follow-up PSG (odds ratio = 1.13, p = 0.004). CONCLUSION: One-third of positional OSA patients who had a high apnea index in the lateral position tends to become nonpositional OSA patients in the follow-up PSG and must be closely monitored if receiving positional therapy only.

Erinacine A-enriched Hericium erinaceus mycelium ameliorates Alzheimer's disease-related pathologies in APPswe/PS1dE9 transgenic mice.

BACKGROUND: The fruiting body of Hericium erinaceus has been demonstrated to possess anti-dementia activity in mouse model of Alzheimer's disease and people with mild cognitive impairment. However, the therapeutic potential of Hericium erinaceus mycelia on Alzheimer's disease remains unclear. In this study, the effects of erinacine A-enriched Hericium erinaceus mycelia (HE-My) on the pathological changes in APPswe/PS1dE9 transgenic mouse model of Alzheimer's disease are studied. RESULTS: After a 30 day oral administration to 5 month-old female APPswe/PS1dE9 transgenic mice, we found that HE-My and its ethanol extracts (HE-Et) attenuated cerebral Aß plaque burden. It's worth noting that the attenuated portion of a plaque is the non-compact structure. The level of insulin-degrading enzyme was elevated by both HE-My and HE-Et in cerebral cortex. On the other hand, the number of plaque-activated microglia and astrocytes in cerebral cortex and hippocampus were diminished, the ratio of nerve growth factor (NGF) to NGF precursor (proNGF) was increased and hippocampal neurogenesis was promoted after these administrations. All the mentioned benefits of these administrations may therefore improve the declined activity of daily living skill in APPswe/PS1dE9 transgenic mice. CONCLUSIONS: These results highlight the therapeutic potential of HE-My and HE-Et on Alzheimer's disease. Therefore, the effective components of HE-My and HE-Et are worth to be developed to become a therapeutic drug for Alzheimer's disease.

Fanconi anemia genes in lung adenocarcinoma- a pathway-wide study on cancer susceptibility.

BACKGROUND: Carcinogens in cigarette smoke can induce the formation of DNA-DNA cross-links, which are repaired by the Fanconi anemia (FA) pathway, and it is tempting to speculate that this pathway is involved in lung tumorigenesis. This study is to determine whether genetic polymorphism of the FA genes is associated with an elevated risk of lung adenocarcinoma, and whether the association between genotypes and risk is modified by exposure to cigarette smoke. METHODS: This case-control study genotyped 53 single-nucleotide polymorphisms (SNPs) in FA genes in 709 patients (354 males and 355 females) with lung adenocarcinoma and in 726 cancer-free individuals (339 males and 387 females). Genotypic frequencies of SNPs were compared between cases and controls to identify important FA genes associated with cancer susceptibility. Joint effects in determining cancer risk contributed by genes and smoking-related risk factors and by multiple genes involved in different FA subpathways were evaluated by multivariate regression analysis and stratified analysis. All analyses were performed on males and females separately, and the comparison of results was considered a way of examining the validity of study findings. RESULTS: Lung adenocarcinomas in both male and female patients were associated with (a) genotypic polymorphisms of FANCC and FANCD1; (b) a combined effect of harboring a higher number of high-risk genotypes and smoking/passive smoking; (c) specific interactions of multiple genes, proteins encoded by which have been known to work jointly within the FA pathway. CONCLUSIONS: Genetic polymorphism of the FA genes is associated with inter-individual susceptibility to lung adenocarcinoma.

Factors responsible for poor sleep quality in patients with chronic obstructive pulmonary disease.

BACKGROUND: Sleep disturbance is a common complaint in patients with chronic obstructive lung disease (COPD). However, the factors resulting in sleep disturbance remain unclear. This retrospective, observational, multicenter study aimed to identify the factors associated with sleep disturbance in patients with COPD. METHODS: The study was a retrospective, observational, and multicenter research. Data including age, sex, body mass index, smoking status, COPD inhaler prescribed, clinical symptoms, pulmonary function tests, medical history of comorbidities, and questionnaires were collected. Parameters including demographics, symptoms, medication, severity, functional classification, and comorbidities were correlated with sleep quality scores. RESULTS: Among 377 patients with COPD, 200 (53 %) patients experienced poor sleep quality (Pittsburg Sleep Quality Index scores > 5). A significant difference in sleep quality, as measured by PSQI scores, was noted between groups based on the 2011 Global Initiatives for Chronic Obstructive Lung Disease (GOLD) classification system. The most common sleep disturbances included "getting up to use the bathroom" (70.3 %), "wake up at night or early morning" (40.3 %), and "cough and snore loudly at night" (15.9 %). The use of inhaled corticosteroids, the presence of wheezing, COPD Assessment Test (CAT) scores, and Modified Medical Research Council (mMRC) dyspnea scale scores positively correlated with poor sleep quality (odds ratio: 1.51, 1.66, 1.09, and 1.30, respectively). Upon multivariate analysis, the CAT score was an independent factor for poor sleep quality in these patients. With the exception of sleep problem items, based on the CAT questionnaire, phlegm was significantly higher in COPD patients with poor sleep quality. CONCLUSIONS: Poor sleep quality is common among patients with COPD and symptoms including wheeze, phlegm, and inhaled corticosteroid use may contribute to poor sleep quality. The CAT score is a good indicator of poor sleep quality in patients with COPD.

The development and psychometric testing of a theory-based instrument to evaluate nurses' perception of clinical reasoning competence.

AIM: The purpose of the study was to develop and psychometrically test the Nurses Clinical Reasoning Scale. BACKGROUND: Clinical reasoning is an essential skill for providing safe and quality patient care. Identifying pre-graduates' and nurses' needs and designing training courses to improve their clinical reasoning competence becomes a critical task. However, there is no instrument focusing on clinical reasoning in the nursing profession. DESIGN: Cross-sectional design was used. This study included the development of the scale, a pilot study that preliminary tested the readability and reliability of the developed scale and a main study that implemented and tested the psychometric properties of the developed scale. METHOD: The Nurses Clinical Reasoning Scale was developed based on the Clinical Reasoning Model. The scale includes 15 items using a Likert five-point scale. Data were collected from 2013-2014. Two hundred and fifty-one participants comprising clinical nurses and nursing pre-graduates completed and returned the questionnaires in the main study. The instrument was tested for internal consistency and test-retest reliability. Its validity was tested with content, construct and known-groups validity. RESULTS: One factor emerged from the factor analysis. The known-groups validity was confirmed. The Cronbach's alpha for the entire instrument was 0·9. CONCLUSION: The reliability and validity of the Nurses Clinical Reasoning Scale were supported. The scale is a useful tool and can be easily administered for the self-assessment of clinical reasoning competence of clinical nurses and future baccalaureate nursing graduates. Study limitations and further recommendations are discussed.

Nutritional supplementation in patients with chronic obstructive pulmonary disease.

Malnutrition in patients with chronic obstructive pulmonary disease (COPD) is associated with cachexia, sarcopenia, and weight loss, and may result in poorer pulmonary function, decreased exercise capacity, and increased risk of exacerbations. Providing nutritional supplementation is an important therapeutic intervention, particularly for severely ill COPD patients with malnutrition. Higher calorie intake through nutritional supplementation significantly increases body weight and muscle strength, and improves quality of life in malnourished COPD patients. Difficulties may be experienced by these COPD patients, who are struggling to breathe and eliminate CO2 from the lungs, resulting in dyspnea, hypercapnia, hypoxia, and respiratory acidosis, which exacerbates muscle loss through oxidative stress and inflammatory responses. To overcome these problems, nutritional supplements should aim to reduce metabolic CO2 production, lower respiratory quotient, and improve lung function. Several studies have shown that high-fat supplements produce less CO2 and have lower respiratory quotient value than high-carbohydrate supplements. In addition, high-fat supplements may be the most efficient means of providing a low-volume, calorie-dense supplement to COPD patients, and may be most beneficial to patients with prolonged mechanical ventilation where hypercapnia and malnutrition are most pronounced. Further studies are required to investigate the optimal nutritional supplements for COPD patients according to their disease severity.