Invasive pulmonary aspergillosis among patients with severe community-acquired pneumonia and influenza in ICUs: a retrospective cohort study.

RATIONALE: The prevalence, clinical characteristics, and outcomes of invasive pulmonary aspergillosis in patients with severe community-acquired pneumonia (CAP) in intensive care units remain underestimated because of the lack of a disease-recognition scheme and the inadequacy of diagnostic tests. OBJECTIVES: To identify the prevalence, risk factors, and outcomes of severe CAP complicated with invasive pulmonary aspergillosis (IPA) in intensive care units (ICUs). METHODS: We conducted a retrospective cohort study including recruited 311 ICU-hospitalized patients with severe CAP without influenza or with influenza. Bronchoalveolar lavage fluid (BALF) samples were from all patients and subjected to mycological testing. Patients were categorized as having proven or probable Aspergillus infection using a modified form of the AspICU algorithm comprising clinical, radiological, and mycological criteria. MEASUREMENTS AND MAIN RESULTS: Of the 252 patients with severe CAP and 59 influenza patients evaluated, 24 met the diagnostic criteria for proven or probable Aspergillus infection in the CAP group and 9 patients in the influenza group, giving estimated prevalence values of 9.5% and 15.3%, respectively. COPD and the use of inhaled corticosteroids were independent risk factors for IPA. IPA in patients with severe CAP was significantly associated with the duration of mechanical support, the length of ICU stay, and the 28-day mortality. CONCLUSIONS: An aggressive diagnostic approach for IPA patients with severe CAP and not only influenza or COVID-19 should be pursued. Further randomized controlled trials need to evaluate the timing, safety, and efficacy of antifungal therapy in reducing IPA incidence and improving clinical outcomes.

Arrayed Pt Single Atoms via Phosphotungstic Acids Intercalated in Silicate Nanochannels for Efficient Hydrogen Evolution Reactions.

Single-atom catalysts, known for their high activity, have garnered significant interest. Currently, single-atom catalysts were prepared mainly on 2D substrates with random distribution. Here, we report a strategy for preparing arrayed single Pt (Pt1) atoms, which are templated through coordination with phosphotungstic acids (PTA) intercalated inside hexagonally packed silicate nanochannels for a high single Pt-atom loading of ca. 3.0 wt %. X-ray absorption spectroscopy, high-angle annular dark-field scanning transmission electron microscopy, and energy-dispersive X-ray spectroscopy, in conjunction with the density-functional theory calculation, collectively indicate that the Pt single atoms are stabilized via a four-oxygen coordination on the PTA within the nanochannels' inner walls. The critical reduction in the Pt-adsorption energy to nearly the cohesive energy of Pt clustering is attributed to the interaction between PTA and the silicate substrate. Consequently, the transition from single-atom dispersion to clustering of Pt atoms can be controlled by adjusting the number density of PTA intercalated within the silicate nanochannels, specifically when the number ratio of Pt atoms to PTA changes from 3.7 to 18. The 3D organized Pt1-PTA pairs, facilitated by the arrayed silicate nanochannels, demonstrate high and stable efficiency with a hydrogen production rate of ca. 300 mmol/h/gPt─approximately twice that of the best-reported Pt efficiency in polyoxometalate-based photocatalytic systems.

Effect of oil extraction methods on walnut oil quality characteristics and the functional properties of walnut protein isolate.

Walnut oils were obtained by supercritical carbon dioxide extraction (SCB), cold-pressing (CP), hexane extraction (HE), and subcritical butane extraction (SBE), and walnut protein isolates (WPI) from the walnut cakes were performed. The results indicate that SCB has the highest oil yield for walnut oil, which was 62.72%, and the total content of trace nutrients (total tocopherols, total phytosterols, and total phenolic compounds) in SCB-walnut oil was also the highest at 2186.75 mg/kg, approximately 1.05 times higher than CP-walnut oil and 1.21 times higher than SBE-walnut oil. Meanwhile, the treatment of WPI with SCB results in a decrease in ß-Sheet and α-Helix structures and an increase in ß-Turn and Random coil structures. Thereby increasing its oil-holding capacity (OHC) and solubility by approximately 1.16 times and 1.27 times compared to CP, respectively. Interestingly, SCB as a green oil production technology, also has good prospects for retaining WPI functionality characteristics.

Low-dose CT screening among never-smokers with or without a family history of lung cancer in Taiwan: a prospective cohort study.

BACKGROUND: In Taiwan, lung cancers occur predominantly in never-smokers, of whom nearly 60% have stage IV disease at diagnosis. We aimed to assess the efficacy of low-dose CT (LDCT) screening among never-smokers, who had other risk factors for lung cancer. METHODS: The Taiwan Lung Cancer Screening in Never-Smoker Trial (TALENT) was a nationwide, multicentre, prospective cohort study done at 17 tertiary medical centres in Taiwan. Eligible individuals had negative chest radiography, were aged 55-75 years, had never smoked or had smoked fewer than 10 pack-years and stopped smoking for more than 15 years (self-report), and had one of the following risk factors: a family history of lung cancer; passive smoke exposure; a history of pulmonary tuberculosis or chronic obstructive pulmonary disorders; a cooking index of 110 or higher; or cooking without using ventilation. Eligible participants underwent LDCT at baseline, then annually for 2 years, and then every 2 years up to 6 years thereafter, with follow-up assessments at each LDCT scan (ie, total follow-up of 8 years). A positive scan was defined as a solid or part-solid nodule larger than 6 mm in mean diameter or a pure ground-glass nodule larger than 5 mm in mean diameter. Lung cancer was diagnosed through invasive procedures, such as image-guided aspiration or biopsy or surgery. Here, we report the results of 1-year follow-up after LDCT screening at baseline. The primary outcome was lung cancer detection rate. The p value for detection rates was estimated by the χ2 test. Univariate and multivariable logistic regression analyses were used to assess the association between lung cancer incidence and each risk factor. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of LDCT screening were also assessed. This study is registered with ClinicalTrials.gov, NCT02611570, and is ongoing. FINDINGS: Between Dec 1, 2015, and July 31, 2019, 12 011 participants (8868 females) were enrolled, of whom 6009 had a family history of lung cancer. Among 12 011 LDCT scans done at baseline, 2094 (17·4%) were positive. Lung cancer was diagnosed in 318 (2·6%) of 12 011 participants (257 [2·1%] participants had invasive lung cancer and 61 [0·5%] had adenocarcinomas in situ). 317 of 318 participants had adenocarcinoma and 246 (77·4%) of 318 had stage I disease. The prevalence of invasive lung cancer was higher among participants with a family history of lung cancer (161 [2·7%] of 6009 participants) than in those without (96 [1·6%] of 6002 participants). In participants with a family history of lung cancer, the detection rate of invasive lung cancer increased significantly with age, whereas the detection rate of adenocarcinoma in situ remained stable. In multivariable analysis, female sex, a family history of lung cancer, and age older than 60 years were associated with an increased risk of lung cancer and invasive lung cancer; passive smoke exposure, cumulative exposure to cooking, cooking without ventilation, and a previous history of chronic lung diseases were not associated with lung cancer, even after stratification by family history of lung cancer. In participants with a family history of lung cancer, the higher the number of first-degree relatives affected, the higher the risk of lung cancer; participants whose mother or sibling had lung cancer were also at an increased risk. A positive LDCT scan had 92·1% sensitivity, 84·6% specificity, a PPV of 14·0%, and a NPV of 99·7% for lung cancer diagnosis. INTERPRETATION: TALENT had a high invasive lung cancer detection rate at 1 year after baseline LDCT scan. Overdiagnosis could have occurred, especially in participants diagnosed with adenocarcinoma in situ. In individuals who do not smoke, our findings suggest that a family history of lung cancer among first-degree relatives significantly increases the risk of lung cancer as well as the rate of invasive lung cancer with increasing age. Further research on risk factors for lung cancer in this population is needed, particularly for those without a family history of lung cancer. FUNDING: Ministry of Health and Welfare of Taiwan.

Polygenic Risk Score, Environmental Tobacco Smoke, and Risk of Lung Adenocarcinoma in Never-Smoking Women in Taiwan.

Importance: Estimating absolute risk of lung cancer for never-smoking individuals is important to inform lung cancer screening programs. Objectives: To integrate data on environmental tobacco smoke (ETS), a known lung cancer risk factor, with a polygenic risk score (PRS) that captures overall genetic susceptibility, to estimate the absolute risk of lung adenocarcinoma (LUAD) among never-smokers in Taiwan. Design, Setting, and Participants: The analyses were conducted in never-smoking women in the Taiwan Genetic Epidemiology Study of Lung Adenocarcinoma, a case-control study. Participants were recruited between September 17, 2002, and March 30, 2011. Data analysis was performed from January 17 to July 15, 2022. Exposures: A PRS was derived using 25 genetic variants that achieved genome-wide significance (P < 5 × 10-8) in a recent genome-wide association study, and ETS was defined as never exposed, exposed at home or at work, and exposed at home and at work. Main Outcomes and Measures: The Individualized Coherent Absolute Risk Estimator software was used to estimate the lifetime absolute risk of LUAD in never-smoking women aged 40 years over a projected 40-year span among the controls by using the relative risk estimates for the PRS and ETS exposures, as well as age-specific lung cancer incidence rates for never-smokers in Taiwan. Likelihood ratio tests were conducted to assess an additive interaction between the PRS and ETS exposure. Results: Data were obtained on 1024 women with LUAD (mean [SD] age, 59.6 [11.4] years, 47.9% ever exposed to ETS at home, and 19.5% ever exposed to ETS at work) and 1024 controls (mean [SD] age, 58.9 [11.0] years, 37.0% ever exposed to ETS at home, and 14.3% ever exposed to ETS at work). The overall average lifetime 40-year absolute risk of LUAD estimated using PRS alone was 2.5% (range, 0.6%-10.3%) among women never exposed to ETS. When integrating both ETS and PRS data, the estimated absolute risk was 3.7% (range, 0.6%-14.5%) for women exposed to ETS at home or work and 5.3% (range, 1.2%-12.1%) for women exposed to ETS at home and work. A super-additive interaction between ETS and the PRS (P = 6.5 × 10-4 for interaction) was identified. Conclusions and Relevance: This study found differences in absolute risk of LUAD attributed to genetic susceptibility according to levels of ETS exposure in never-smoking women. Future studies are warranted to integrate these findings in expanded risk models for LUAD.

Vancomycin associated acute kidney injury in patients with infectious endocarditis: a large retrospective cohort study.

Background: Vancomycin remains the cornerstone antibiotic for the treatment of infective endocarditis (IE). Vancomycin has been associated with significant nephrotoxicity. However, vancomycin associated acute kidney injury (AKI) has not been evaluated in patients with IE. We conducted this large retrospective cohort study to reveal the incidence, risk factors, and prognosis of vancomycin-associated acute kidney injury (VA-AKI) in patients with IE. Methods: Adult patients diagnosed with IE and receiving vancomycin were included. The primary outcome was VA-AKI. Results: In total, 435 of the 600 patients were enrolled. Of these, 73.6% were male, and the median age was 52 years. The incidence of VA-AKI was 17.01% (74). Only 37.2% (162) of the patients received therapeutic monitoring of vancomycin, and 30 (18.5%) patients had reached the target vancomycin trough concentration. Multiple logistic regression analysis revealed that body mass index [odds ratio (OR) 1.088, 95% CI 1.004, 1.179], duration of vancomycin therapy (OR 1.030, 95% CI 1.003, 1.058), preexisting chronic kidney disease (OR 2.291, 95% CI 1.018, 5.516), admission to the intensive care unit (OR 2.291, 95% CI 1.289, 3.963) and concomitant radiocontrast agents (OR 2.085, 95% CI 1.093, 3.978) were independent risk factors for VA-AKI. Vancomycin variety (Lai Kexin vs. Wen Kexin, OR 0.498, 95% CI 0.281, 0.885) were determined to be an independent protective factor for VI-AKI. Receiver operator characteristic curve analysis revealed that duration of therapy longer than 10.75 days was associated with a significantly increased risk of VA-AKI (HR 1.927). Kidney function was fully or partially recovered in 73.0% (54) of patients with VA-AKI. Conclusion: The incidence of VA-AKI in patients with IE was slightly higher than in general adult patients. Concomitant contrast agents were the most alarmingly nephrotoxic in patients with IE, adding a 2-fold risk of VA-AKI. In patients with IE, a course of vancomycin therapy longer than 10.75 days was associated with a significantly increased risk of AKI. Thus, closer monitoring of kidney function and vancomycin trough concentrations was recommended in patients with concurrent contrast or courses of vancomycin longer than 10.75 days.

Low-Dose Computed Tomography Screening in Relatives With a Family History of Lung Cancer.

INTRODUCTION: The role of a family history of lung cancer (LCFH) in screening using low-dose computed tomography (LDCT) has not been prospectively investigated with long-term follow-up. METHODS: A multicenter prospective study with up to three rounds of annual LDCT screening was conducted to determine the detection rate of lung cancer (LC) in asymptomatic first- or second-degree relatives of LCFH. RESULTS: From 2007 to 2011, there were 1102 participants enrolled, including 805 and 297 from simplex and multiplex families (MFs), respectively (54.2% women and 70.0% never-smokers). The last follow-up date was May 5, 2021. The overall LC detection rate was 4.5% (50 of 1102). The detection rate in MF was 9.4% (19 of 202) and 4.4% (4 of 91) in never-smokers and in those who smoked, respectively. The corresponding rates for simplex families were 3.7% (21 of 569) and 2.7% (6 of 223), respectively. Of these, 68.0% and 22.0% of cases with stage I and IV diseases, respectively. LC diagnoses within a 3-year interval from the initial screening tend to be younger, have a higher detection rate, and have stage I disease; thereafter, more stage III-IV disease and 66.7% (16 of 24) with negative or semipositive nodules in initial computed tomography scans. Within the 6-year interval, only maternal (modified rate ratio = 4.46, 95% confidence interval: 2.32-8.56) or maternal relative history of LC (modified rate ratio = 5.41, 95% confidence interval: 2.84-10.30) increased the risk of LC. CONCLUSIONS: LCFH is a risk factor for LC and is increased with MF history, among never-smokers, younger adults, and those with maternal relatives with LC. Randomized controlled trials are needed to confirm the mortality benefit of LDCT screening in those with LCFH.

Serum vascular endothelial growth factor affects tissue fluid accumulation and is associated with deteriorating tissue perfusion and oxygenation in severe sepsis: a prospective observational study.

BACKGROUND: Positive fluid balance and tissue fluid accumulation are associated with adverse outcomes in sepsis. Vascular endothelial growth factor (VEGF) increases in sepsis, promotes vascular permeability, and may affect tissue fluid accumulation and oxygenation. We used near-infrared spectroscopy (NIRS) to estimate tissue hemoglobin (Hb) oxygenation and water (H2O) levels to investigate their relationship with serum VEGF levels. MATERIAL AND METHODS: New-onset severe sepsis patients admitted to the intensive care unit were enrolled. Relative tissue concentrations of oxy-Hb ([HbO2]), deoxy-Hb ([HbR]), total Hb ([HbT]), and H2O ([H2O]) were estimated by near-infrared spectroscopy (NIRS) for three consecutive days and serum VEGF levels were measured. Comparisons between oliguric and non-oliguric patients were conducted and the correlations between variables were analyzed. RESULTS: Among 75 eligible patients, compared with non-oliguric patients, oliguric patients were administrated more intravascular fluids (median [IQR], 1926.00 [1348.50-3092.00] mL/day vs. 1069.00 [722.00-1486.75] mL/day, p < 0.001) and had more positive daily net intake and output (mean [SD], 1,235.06 [1303.14] mL/day vs. 313.17 [744.75] mL/day, p = 0.012), lower [HbO2] and [HbT] over the three-day measurement (analyzed by GEE p = 0.01 and 0.043, respectively) and significantly higher [H2O] on the third day than on the first two days (analyzed by GEE p = 0.034 and 0.018, respectively). Overall, serum VEGF levels were significantly negatively correlated with [HbO2] and [HbT] (rho = - 0.246 and - 0.266, p = 0.042 and 0.027, respectively) but positively correlated with [H2O] (rho = 0.449, p < 0.001). Subgroup analysis revealed a significant correlation between serum VEGF and [H2O] in oliguric patients (rho = 0.532, p = 0.003). Multiple regression analysis determined the independent effect of serum VEGF on [H2O] (standardized coefficient = 0.281, p = 0.038). CONCLUSIONS: In severe sepsis, oliguria relates to higher positive fluid balance, lower tissue perfusion and oxygenation, and progressive tissue fluid accumulation. Elevated serum VEGF is associated with worsening tissue perfusion and oxygenation and independently affects tissue fluid accumulation.

Appraisal of lung cancer survival in patients with end-stage renal disease.

Introduction: The survival outcome of lung cancer patients with end-stage renal disease has been poorly studied in the literature. In this study, we evaluated the effect of end-stage renal disease on lung cancer survival. Material and methods: A retrospective, multicenter, matched-cohort study of lung cancer patients with end-stage renal disease under renal replacement therapy (WITH-ESRD) and without end-stage renal disease (WITHOUT-ESRD) was performed. One WITH-ESRD patient was matched to four WITHOUT-ESRD patients. Results: Baseline clinical characteristics did not differ statistically significantly after matching between the WITH-ESRD and WITHOUT-ESRD groups. WITH-ESRD included 133 patients and WITHOUT-ESRD included 532 patients. Kaplan-Meier survival analysis demonstrated no significant difference in median overall survival between WITH-ESRD patients and WITHOUT-ESRD patients (7.36 months versus 12.25 months, respectively, p = 0.133). Lung cancer WITH-ESRD patients receiving medical treatment had a median overall survival of 5.98 months (95% CI: 4.34-11.76) compared to 14.13 months (95% CI: 11.30-16.43) for WITHOUT-ESRD patients, p = 0.019. Although patients receiving surgical treatment compared to those receiving medical treatment had an improvement of survival by 46% (HR = 0.54, 95% CI: 0.19-1.53, p = 0.243), the difference did not reach statistical significance. Cox regression analysis revealed that male gender and stage IIIA-IV were independent factors associated with poor outcome for WITH-ESRD patients. Conclusions: In our limited experience, the survival for lung cancer with ESRD is not inferior to lung cancer patients without ESRD. The reasons for poor survival for the WITH-ESRD medical treatment group and late diagnosis despite frequent medical visits merit further investigation.

The impacts of bacterial co-infections and secondary bacterial infections on patients with severe influenza pneumonitis admitted to the intensive care units.

PURPOSES: This study investigated the prevalence and clinical outcomes of pulmonary bacterial co-infections and secondary bacterial infections in patients with severe influenza pneumonitis. METHODS: We retrospectively analyzed the data of adult patients with severe influenza pneumonitis admitted to medical ICUs. Bacterial co-infections and secondary bacterial infections were identified. The risk factors of bacterial infection were evaluated. The outcomes of patients regarding co-infection or secondary bacterial infection were analyzed. RESULTS: We identified 117 critically ill patients with laboratory-confirmed influenza pneumonitis admitted to the medical ICUs. Klebsiella pneumoniae (31.4%) and Staphylococcus aureus (22.8%) were the most identified bacteria in patients with bacterial co-infection. A high proportion of methicillin-resistant Staphylococcus aureus (17.1%) was noted. Liver cirrhosis and diabetes mellitus were the independent risk factors for bacterial co-infection. Acinetobacter baumannii (30.7%) and S. aureus (23.1%) were the most often identified bacteria in patients with secondary bacterial pneumonia. Patients with secondary bacterial infections had a longer duration of mechanical ventilation, and longer ICU and hospital stay. CONCLUSIONS: High rates of drug-resistant bacterial co-infections and secondary bacterial infections were identified in patients with severe influenza pneumonitis requiring ICU care and were associated with more morbidity in these patients.

Increased tissue water in patients with severe sepsis affects tissue oxygenation measured by near-infrared spectroscopy: a prospective, observational case-control study.

Background: Tissue oedema affects tissue perfusion and interferes with the monitoring of tissue oxygenation in patients with severe sepsis. However, the underlying mechanisms remain unclear. We used a wireless near-infrared spectroscopy (NIRS) device that transmits tri-wavelength light to quantify tissue haemoglobin (Hb) and water (H2O) content. We estimated tissue H2O in severe sepsis patients and healthy controls, compared their difference, and investigated the correlation of tissue H2O with systemic haemodynamics and its impact on tissue oxygenation. Methods: Seventy-seven adult patients with new-onset severe sepsis admitted to the intensive care unit within 72 h and 30 healthy volunteers (controls) were enrolled. The NIRS device was placed on the participant's leg to estimate the relative tissue concentrations of oxy-Hb ([HbO2]), deoxy-Hb ([HbR]), total Hb ([HbT]), and H2O ([H2O]) at rest for three consecutive days. Two-sample t-test or Mann-Whitney U test, chi-square test, and generalised estimating equations (GEEs) were used for comparisons. Results: In severe sepsis patients, the [H2O] in the anterior tibia was higher [mean (standard deviation, 95% confidence interval), 10.57 (3.37, 9.81-11.34) vs. 7.40 (1.89, 6.70-8.11)] and the [HbO2], [HbT], and tissue Hb oxygen saturation (StO2) were lower [0.20 (0.01, 0.20-0.20) vs. 0.22 (0.01, 0.22-0.23), 0.42 (0.02, 0.42-0.43) vs. 0.44 (0.02, 0.44-0.45), and 47.25% (1.97%, 46.80-47.70%) vs. 49.88% (1.26%, 49.41-50.35%), respectively] than in healthy controls in first-day measurements. GEE analysis revealed significant differences in [H2O], [HbO2], [HbT], and StO2 between groups over three consecutive days (all P≤0.001). In addition, [HbO2] and StO2 levels gradually decreased over time in the patient group. A negative correlation was observed between [H2O] and [HbO2] and StO2, which became more obvious over time (day 1: r=-0.51 and r=-0.42, respectively; both P<0.01; day 3: r=-0.67 and r=-0.63, respectively, both P<0.01). Systolic arterial pressure was positively related to [H2O] (r=0.51, P<0.05, on day 1) but was not associated with tissue oxygenation parameters. Conclusions: NIRS can be used to quantify tissue H2O. Severe sepsis patients have increased tissue H2O, which responds to changes in arterial blood pressure and affects tissue oxygenation.

Association between socioeconomic status and mental health among China's migrant workers: A moderated mediation model.

Mental health problems are prevalent among China's internal migrant workers. However, research on the relationship between socioeconomic status (SES) and mental health is insufficient. Therefore, this study, utilizing the China's National Dynamic Monitoring Survey data from a sample of 15,997 migrant workers aged 15-59 years to explore differences in the relationship between migrants' objective and subjective SES and mental health status in 2015. Both the mediating effect of perceived interpersonal discrimination and the moderating effect of age were examined through structural equation modeling. The results indicated that subjective SES has a stronger direct relationship with mental health than objective SES. Perceived interpersonal discrimination mediated the association between subjective SES and mental health. Furthermore, a much stronger relationship was found between subjective SES and perceived interpersonal discrimination among migrants older than 24 years of age than younger migrant groups. The results showed that, compared with traditional objective SES indicators, subjective SES could be a more sensitive index for identifying those migrant workers with a high risk of mental health problems. In addition, reducing interpersonal discrimination toward migrants can alleviate their mental health problems. And we should pay more attention to older migrant workers since they are more likely to prone to interpersonal discrimination and mental health issues.

Recalibrating Risk Prediction Models by Synthesizing Data Sources: Adapting the Lung Cancer PLCO Model for Taiwan.

BACKGROUND: Methods synthesizing multiple data sources without prospective datasets have been proposed for absolute risk model development. This study proposed methods for adapting risk models for another population without prospective cohorts, which would help alleviate the health disparities caused by advances in absolute risk models. To exemplify, we adapted the lung cancer risk model PLCOM2012, well studied in the west, for Taiwan. METHODS: Using Taiwanese multiple data sources, we formed an age-matched case-control study of ever-smokers (AMCCSE), estimated the number of ever-smoking lung cancer patients in 2011-2016 (NESLP2011), and synthesized a dataset resembling the population of cancer-free ever-smokers in 2010 regarding the PLCOM2012 risk factors (SPES2010). The AMCCSE was used to estimate the overall calibration slope, and the requirement that NESLP2011 equals the estimated total risk of individuals in SPES2010 was used to handle the calibration-in-the-large problem. RESULTS: The adapted model PLCOT-1 (PLCOT-2) had an AUC of 0.78 (0.75). They had high performance in calibration and clinical usefulness on subgroups of SPES2010 defined by age and smoking experience. Selecting the same number of individuals for low-dose computed tomography screening using PLCOT-1 (PLCOT-2) would have identified approximately 6% (8%) more lung cancers than the US Preventive Services Task Forces 2021 criteria. Smokers having 40+ pack-years had an average PLCOT-1 (PLCOT-2) risk of 3.8% (2.6%). CONCLUSIONS: The adapted PLCOT models had high predictive performance. IMPACT: The PLCOT models could be used to design lung cancer screening programs in Taiwan. The methods could be applicable to other cancer models.

Studies of high-membered two-dimensional Ruddlesden-Popper Cs7Pb6I19 perovskite nanosheets via kinetically controlled reactions.

Two-dimensional (2D) all-inorganic Ruddlesden-Popper (RP) perovskite Cs7Pb6I19 nanosheets (NSs) were successfully developed for the first time by employing a structural recrystallization process with additional passivation of small organic sulfide molecules. The structure of Cs7Pb6I19 NSs is confirmed by powder X-ray diffraction measurements, atomically-resolved STEM measurements and atomic force microscopy (AFM) studies. Cs7Pb6I19 NSs with a specific n value of 6 exhibits unique absorption and emission spectra with intense excitons at 560 nm due to quantum confinement effects in 2D perovskite slabs. The formation mechanisms of 2D Cs7Pb6I19 NSs and 3D γ-CsPbI3 phases were investigated by in situ photoluminescence (PL) spectroscopy and the activation energies of their formation reactions were calculated to be 151 kJ mol-1 and 95.3 kJ mol-1, respectively. The phase stability of 2D Cs7Pb6I19 NSs can be maintained at temperatures below 14 °C for more than 4 weeks. The overall results indicate that 2D Cs7Pb6I19 NSs demonstrate unique optical properties and structural stability compared with other 3D perovskite materials. We have opened a new path to the future discovery of 2D perovskite structures with metastable phases by using this recrystallization method and the assistance of sulfur-derived organic molecules.

The potential and limitation of targeted chromosomal breakpoint sequencing for the ROS1 fusion gene identification in lung cancer.

ROS1 fusion genes are rare but important driver genes in lung cancer. Owing to their rarity, many clinicopathological features and treatment responses for each ROS1 fusion variant are still largely unknown and require further investigation. RNA is the preferable template for the ROS1 fusion gene screening, but deterioration of RNA in FFPE often makes the detection challenging. To resolve the difficulty, a targeted chromosomal breakpoint sequencing method was developed for searching the ROS1 fusion gene, and was compared with fluorescence in situ hybridization, immunohistochemistry, RT-qPCR using 260 lung cancer samples of Southern Taiwan. The results showed that ROS1-altered cases were present at low frequencies, did not share distinct clinicopathological features, and often carried other driver mutations. The performance of the targeted sequencing assay was superior to the RT-qPCR in ROS1 fusion gene identification when the cDNAs were from FFPE samples, but long-read DNA sequencing and fresh-frozen samples would be better to revolve all fusion genes. Precise determination of all ROS1 fusion variants and concomitant driver mutations using both genomic DNA and RNA would be required to help improve the treatment of patients with ROS1 alterations.

Comparing Clinical Outcomes of Tiotropium/Olodaterol, Umeclidinium/Vilanterol, and Indacaterol/Glycopyrronium Fixed-Dose Combination Therapy in Patients with Chronic Obstructive Pulmonary Disease in Taiwan: A Multicenter Cohort Study.

Background: Long-acting beta-agonists (LABA) and long-acting muscarinic antagonists (LAMA) combination therapy improved lung function and health-related quality-of-life and reduced exacerbation rates and dyspnea in symptomatic chronic obstructive pulmonary disease (COPD) patients. We compared the real-world effects of three fixed-dose LABA/LAMA combinations for COPD in Taiwan. Methods: This multicenter, retrospective study evaluated 1-year outcomes after LABA/LAMA combination therapy in patients with symptomatic COPD. Exacerbations and symptoms of COPD, lung functions, and therapy escalation were compared among patients using tiotropium/olodaterol, umeclidinium/vilanterol and indacaterol/glycopyrronium. Propensity score matching (PSM) was applied to balance the baseline characteristics. Results: Data of 1,617 patients were collected. After PSM, time to first moderate-to-severe COPD exacerbation was comparable among three groups, while the annualized rates of the exacerbation (episodes/patient/year) in patients receiving tiotropium/olodaterol (0.19) or umeclidinium/vilanterol (0.17) were significantly lower than those receiving indacaterol/glycopyrronium (0.38). COPD-related symptoms were stable over the treatment period, and there was no significant difference in the changes of symptom scores including CAT and mMRC among three groups at the end of the study period. Conclusion: This study presented valuable real-world outcome in terms of exacerbation and treatment response of COPD patients treated with fixed-dose LABA/LAMA regimens in Taiwan. The annualized rates of moderate-to-severe exacerbation in patients receiving tiotropium/olodaterol or umeclidinium/vilanterol were significantly lower than those receiving indacaterol/glycopyrronium, though the time to first moderate-to-severe exacerbation was similar among different fixed-dose LABA/LAMA combinations.

Mechanisms of immune regulation for acupuncture on chronic respiratory diseases.

Chronic respiratory diseases (CRDs) are among the most common noncommunicable diseases globally, with high morbidity and mortality rates. Acupuncture, a treatment method derived from Traditional Chinese Medicine, has been shown to be effective at treating CRDs, with little risk of adverse effects. Scientific research on the mechanisms underlying the effects of acupuncture, especially, its immune regulatory function, has rapidly advanced in recent years. Herein, the diverse immune regulatory mechanisms underlying the beneficial effects of acupuncture are summarized from the perspectives of innate immunity, adaptive immunity, and neuroimmunity. A better understanding of these mechanisms will ultimately provide a scientific basis for the clinical use of acupuncture for the treatment of CRDs.

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.

18F-Fluorodeoxyglucose PET/CT for Early Prediction of Outcomes in Patients with Advanced Lung Adenocarcinomas and EGFR Mutations Treated with First-Line EGFR-TKIs.

This study aims to investigate the role of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) in early prediction of response and survival following epithelial growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) therapy in patients with advanced lung adenocarcinomas and EGFR mutations. Thirty patients with stage IIIB/IV lung adenocarcinomas and EGFR mutations receiving first-line EGFR-TKIs were prospectively evaluated between November 2012 and May 2015. EGFR mutations were quantified by delta cycle threshold (dCt). 18F-FDG PET/CT was performed before and 2 weeks after treatment initiation. PET response was assessed based on PET Response Criteria in Solid Tumors (PERCIST). Baseline and percentage changes in the summed standardized uptake value, metabolic tumor volume (bsumMTV and ΔsumMTV, respectively), and total lesion glycolysis of ≤5 target lesions/patient were calculated. The association between parameters (clinical and PET) and non-progression disease after 3 months of treatment in CT based on the Response Evaluation Criteria in Solid Tumors Version 1.1 (nPD3mo), progression-free survival (PFS), and overall survival (OS) were tested. The median follow-up time was 19.6 months. The median PFS and OS were 12.0 and 25.3 months, respectively. The PERCIST criteria was an independent predictor of nPD3mo (p = 0.009), dCt (p = 0.014) and bsumMTV (p = 0.014) were independent predictors of PFS, and dCt (p = 0.014) and ΔsumMTV (p = 0.005) were independent predictors of OS. 18F-FDG PET/CT achieved early prediction of outcomes in patients with advanced lung adenocarcinomas and EGFR mutations receiving EGFR-TKIs.

Vitrectomy with residual internal limiting membrane covering and autologous blood for a secondary macular hole: A case report.

BACKGROUND: Myopic foveoschisis (MF) is a common complication of pathological myopia. A macular hole (MH) usually results from the natural progression of MF and is a common complication of vitrectomy. Vitrectomy combined with residual internal limiting membrane (ILM) covering and autologous blood was effective for closing a secondary MH. CASE SUMMARY: A 52-year-old woman presented to our clinic with a complaint of blurred vision in the right eye for 7 years. Her best corrected visual acuity (BCVA) was 20/100, axial length was 25.79 mm and standard equivalent refractive error was -10.5 dioptres. Preoperative optical coherence tomography revealed foveoschisis in the right eye. Vitrectomy with fovea-sparing ILM peeling was performed. An MH developed and gradually expanded 5 mo after the initial vitrectomy. Vitrectomy with residual ILM covering and autologous blood was performed. The MH closed 3 wk after the second vitrectomy. CONCLUSION: Fovea-sparing ILM peeling can provide residual ILM for the treatment of MH secondary to vitrectomy for MF. Vitrectomy combined with residual ILM covering and autologous blood is effective for closing secondary MH and improving BCVA.