Aqueous extract of Descuraniae Semen attenuates lipopolysaccharide-induced inflammation by inhibiting ER stress and WNK4-SPAK-NKCC1 pathway.

Sepsis causes systemic inflammatory responses and acute lung injury (ALI). Despite modern treatments, sepsis-related ALI mortality remains high. Aqueous extract of Descuraniae Semen (AEDS) exerts anti-endoplasmic reticulum (ER) stress, antioxidant and anti-inflammatory effects. AEDS alleviates inflammation and oedema in ALI. Sodium-potassium-chloride co-transporter isoform 1 (NKCC1) is essential for regulating alveolar fluid and is important in ALI. The NKCC1 activity is regulated by upstream with-no-lysine kinase-4 (WNK4) and STE20/SPS1-related proline/alanine-rich kinase (SPAK). This study aimed to investigate the effects of AEDS on lipopolysaccharide (LPS)-induced ALI model in A549 cells, considering the regulation of ER stress, WNK4-SPAK-NKCC1 cascades, inflammation and apoptosis. Cell viability was investigated by the CCK-8 assay. The expressions of the proteins were assessed by immunoblotting analysis assays. The levels of pro-inflammatory cytokines were determined by ELISA. The expression of cytoplasmic Ca2+ in A549 cells was determined using Fluo-4 AM. AEDS attenuates LPS-induced inflammation, which is associated with increased pro-inflammatory cytokine expression and activation of the WNK4-SPAK-NKCC1 pathway. AEDS inhibits the WNK4-SPAK-NKCC1 pathway by regulating of Bcl-2, IP3R and intracellular Ca2+. WNK4 expression levels are significantly higher in the WNK4-overexpressed transfected A549 cells and significantly decrease after AEDS treatment. AEDS attenuates LPS-induced inflammation by inhibiting the WNK4-SPAK-NKCC1 cascade. Therefore, AEDS is regarded as a potential therapeutic agent for ALI.

Microbiome signatures associated with clinical stages of gastric Cancer: whole metagenome shotgun sequencing study.

BACKGROUND: Gastric cancer is one of the global health concerns. A series of studies on the stomach have confirmed the role of the microbiome in shaping gastrointestinal diseases. Delineation of microbiome signatures to distinguish chronic gastritis from gastric cancer will provide a non-invasive preventative and treatment strategy. In this study, we performed whole metagenome shotgun sequencing of fecal samples to enhance the detection of rare bacterial species and increase genome sequence coverage. Additionally, we employed multiple bioinformatics approaches to investigate the potential targets of the microbiome as an indicator of differentiating gastric cancer from chronic gastritis. RESULTS: A total of 65 patients were enrolled, comprising 33 individuals with chronic gastritis and 32 with gastric cancer. Within each group, the chronic gastritis group was sub-grouped into intestinal metaplasia (n = 15) and non-intestinal metaplasia (n = 18); the gastric cancer group, early stage (stages 1 and 2, n = 13) and late stage (stages 3 and 4, n = 19) cancer. No significant differences in alpha and beta diversities were detected among the patient groups. However, in a two-group univariate comparison, higher Fusobacteria abundance was identified in phylum; Fusobacteria presented higher abundance in gastric cancer (LDA scored 4.27, q = 0.041 in LEfSe). Age and sex-adjusted MaAsLin and Random Forest variable of importance (VIMP) analysis in species provided meaningful features; Bacteria_caccae was the most contributing species toward gastric cancer and late-stage cancer (beta:2.43, se:0.891, p:0.008, VIMP score:2.543). In contrast, Bifidobacterium_longum significantly contributed to chronic gastritis (beta:-1.8, se:0.699, p:0.009, VIMP score:1.988). Age, sex, and BMI-adjusted MasAsLin on metabolic pathway analysis showed that GLCMANNANAUT-PWY degradation was higher in gastric cancer and one of the contributing species was Fusobacterium_varium. CONCLUSION: Microbiomes belonging to the pathogenic phylum Fusobacteria and species Bacteroides_caccae and Streptococcus_anginosus can be significant targets for monitoring the progression of gastric cancer. Whereas Bifidobacterium_longum and Lachnospiraceae_bacterium_5_1_63FAA might be protection biomarkers against gastric cancer.

Pulmonary rehabilitation improves exercise capacity, health-related quality of life, and cardiopulmonary function in patients with non-small cell lung cancer.

BACKGROUND: Lung cancer significantly impairs exercise capacity and health-related quality of life (HRQL). Pulmonary rehabilitation (PR) has demonstrated positive effects on exercise capacity and HRQL in lung cancer patients. However, its impact on cardiopulmonary function needs further exploration. The aim of this study was to explore the effects of PR on cardiopulmonary function, exercise capacity and HRQL in patients with lung cancer. METHODS: Patients with lung cancer were enrolled in a 12-week PR program. Each participant underwent a thorough evaluation, which included spirometry, cardiopulmonary exercise testing, respiratory muscle strength test, and evaluation of HRQL using the Chronic Obstructive Pulmonary Disease Assessment Test (CAT). RESULTS: Fifty-six patients completed the PR program. Following PR, exercise capacity significantly improved, as evidenced by increased peak oxygen uptake and work rate (both p < 0.05). Exertional symptoms were notably reduced, including leg soreness and dyspnea at peak exercise, accompanied by a decrease in the CAT score (all p < 0.05). Furthermore, improvements in cardiopulmonary function were observed, encompassing respiratory muscle strength, ventilatory equivalent, tidal volume, stroke volume index, and cardiac index at peak exercise (all p < 0.05). CONCLUSIONS: PR demonstrated notable enhancements in cardiopulmonary function, exertional symptoms, exercise capacity, and HRQL in patients with lung cancer.

Validating the Baveno Elastography Criteria of Advanced Liver Fibrosis in Two-Dimensional Shear Wave Elastography: A Prospective Pathology-Based Study.

INTRODUCTION: The Baveno criteria for assessing advanced liver fibrosis were mainly determined by transient elastography (TE), and its pathology-based validation studies in two-dimensional shear wave elastography (2D-SWE) remain limited. We aimed to validate the Baveno criteria through use of 2D-SWE. METHOD: Consecutive patients who underwent liver biopsies for various benign liver diseases were prospectively recruited. Liver stiffness measurement (LSM) was simultaneously evaluated by TE and 2D-SWE. The optimal cutoff value to predict advanced liver fibrosis was determined by the Youden Index, and the diagnostic performance was estimated using area under the receiver operating characteristic (AUROC) analysis. RESULTS: A total of 101 patients were enrolled having a median age of 55.0 (IQR: 46.0-63.5) years, with 53 (52.48%) of them being male. Using <9 and >14 kPa as the optimal dual cutoffs, the AUROC values in TE and 2D-SWE were 0.92 (95% CI: 0.83-0.97) and 0.93 (95% CI: 0.84-0.98), respectively (p = 0.61). The sensitivity and specificity of LSM by TE/2D-SWE achieved rates of 94.44%/94.44% and 86.00%/88.00%, respectively. However, using the Baveno criteria, the AUROC values in TE and 2D-SWE could remain achieving 0.91 (95% CI: 0.82-0.97) and 0.93 (95% CI: 0.84-0.98), respectively (p = 0.36). The sensitivity and specificity in TE/2D-SWE were 88.24%/88.24% and 86.79%/90.57%, respectively. CONCLUSION: This study establishes the compatibility of the Baveno dual cutoff criteria with 2D-SWE, positioning it as an easily used criteria in clinical practice and research.

The effectiveness of a virtual reality teaching module on advance care planning and advance decision for medical professionals.

BACKGROUND: The concepts of advance care planning (ACP) and advance decisions/directives (ADs) are widely recognized around the world. The Patient Right to Autonomy Act in Taiwan, the first of its kind in Asia, went into effect in 2019. However, a lack of knowledge and confidence regarding ACP and ADs is a barrier for medical professionals in discussing ACP and ADs with their patients. In addition, in Asian countries, physicians tend to make family-centered decisions, which influence how they can implement ADs. METHODS: Virtual reality (VR) is known for its immersive and interactive simulation experience and can upgrade medical education. We developed a VR teaching module to help medical professionals better understand ACP and ADs, with assessment tools integrated into the module. The participants were asked to answer seven knowledge items embedded in the module and fill out the surveys regarding attitudes toward ACP and ADs and confidence in implementing ADs before and after the module. They also reported behaviors related to ADs before and three months after the VR experience. RESULTS: From July 2020 to June 2022, 30 physicians and 59 nurses joined the study, and 78.7% of them had no prior experience in hospice care. After learning from the VR module, all 89 participants were able to answer all seven items correctly. The results showed a slightly more positive attitude toward ACP and ADs (scores: 32.29 ± 3.80 versus 33.06 ± 3.96, p < .05) and more confidence in implementing ADs (scores: 13.96 ± 2.68 versus 16.24 ± 2.67, p < .001) after the VR module. Changes in AD-related behaviors (scores: 11.23 ± 4.01 versus 13.87 ± 4.11, p < .001) were also noted three months after the VR experience. CONCLUSIONS: This study found that medical professionals may have better knowledge of ACP and ADs, slightly improved attitudes toward ACP and ADs, and greater confidence in implementing ADs after experiencing the VR module. Most importantly, the findings suggested that using a VR format may help motivate medical professionals to perform essential behaviors related to ADs, including introducing ADs to their patients and discussing ADs with their own family.

Comparison of therapeutic outcomes in esophageal squamous cell carcinoma following neoadjuvant chemoradiotherapy: A prospective observational cohort study.

BACKGROUND: Patients with locally advanced esophageal squamous cell carcinoma (ESCC) following neoadjuvant chemoradiotherapy (nCRT) may not always receive resection despite the possible achievement of a pathologic complete response (pCR) being associated with superior survival benefit. We aimed to compare outcomes among ESCC patients with or without pCR and those refusing surgery. METHODS: In total, 111 medically operable, non-cervical ESCC patients after the same protocol of nCRT (platinum/5-fluorouracil plus radiation 50Gy) were prospectively enrolled between 2011 and 2021. Eighty-three of them underwent esophagectomy comprising pCR (n = 32) and non-pCR (n = 51), while 28 operable patients declined surgery (refusal-of-surgery group). Predictors and survival data were analyzed. RESULTS: In terms of esophagectomy, 38.5% (32/83) patients achieved pCR. The pCR group exhibited better pretreatment performance status than the non-pCR group (adjusted odds ratio: 0.11, 95% confidence interval: 0.03-0.58; p = 0.01). Among pCR, non-pCR, and refusal-of-surgery groups, the 5-year overall survival (OS) rates were 56%, 29% and 50% (p = 0.08) and progression-free survival (PFS) rates were 52%, 28% and 36% (p = 0.07) respectively. The pCR group had significantly better OS and PFS than the non-PCR group (adjusted hazard ratio: 2.33 and 1.93, p = 0.02 and 0.049 respectively) but not the refusal-of-surgery group. CONCLUSION: Better pretreatment performance status is associated with higher chance of pCR. Consistent with previous studies, we found attainment of pCR confers the best OS and PFS. Suboptimal OS in the refusal-of-surgery group reflects some of them would have residual disease in addition to complete remission. Further studies are needed to identify prognostic factors of pCR to select candidates who could validly decline esophagectomy.

A real-world study of Afatinib plus ramucirumab in treatment-naïve, EGFR-mutated, non-small cell lung cancer.

BACKGROUND: Recent reports suggested combining ramucirumab with epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) to overcome EGFR resistance in non-small cell lung cancer (NSCLC). Nonetheless, evidence supporting the activity of afatinib and ramucirumab is lacking. This study investigated the survival benefits and safety profile of afatinib plus ramucirumab in patients with treatment-naïve, EGFR-mutated, metastatic NSCLC. MATERIALS AND METHODS: The medical records of patients with EGFR-mutated NSCLC were retrospectively retrieved. Patients who received first-line sequential afatinib followed by ramucirumab and the first-line combination of afatinib plus ramucirumab were included. The Kaplan-Meier was used to estimate the progression-free survival (PFS) of all included patients, patients on sequential afatinib followed by ramucirumab (PFS1), and patients on the up-front combination of afatinib and ramucirumab (PFS2). RESULTS: Thirty-three patients were included (25 women; median age: 63 [45-82] years). The median follow-up of the included patients was 17 months (range 6-89 months). the median PFS for the whole cohort was 71 months (95% CI 67.2-74.8) with eight events during the follow-up. The median PFS1 and PFS2 were 71 months (95 CI not defined) and 26 months (95% CI 18.6-33.4), respectively. In terms of OS, the median OS for all patients and patients on sequential treatment was not defined, while the median OS for patients on upfront combination was 30 months (95% CI 20.9-39.1). There was no significant association between EGFR mutation type and PFS1 or PFS2. CONCLUSIONS: Afatinib plus ramucirumab could improve the PFS of patients with EGFR-positive NSCLC at a predictable safety profile. Our data also suggest a survival benefit of adding ramucirumab to afatinib in patients with uncommon mutations, which should be investigated further.

Editor's Choice - Infective Native Aortic Aneurysms: A Delphi Consensus Document on Terminology, Definition, Classification, Diagnosis, and Reporting Standards.

OBJECTIVE: There is no consensus regarding the terminology, definition, classification, diagnostic criteria, and algorithm, or reporting standards for the disease of infective native aortic aneurysm (INAA), previously known as mycotic aneurysm. The aim of this study was to establish this by performing a consensus study. METHODS: The Delphi methodology was used. Thirty-seven international experts were invited via mail to participate. Four two week Delphi rounds were performed, using an online questionnaire, initially with 22 statements and nine reporting items. The panellists rated the statements on a five point Likert scale. Comments on statements were analysed, statements revised, and results presented in iterative rounds. Consensus was defined as ≥ 75% of the panel selecting "strongly agree" or "agree" on the Likert scale, and consensus on the final assessment was defined as Cronbach's alpha coefficient > .80. RESULTS: All 38 panellists completed all four rounds, resulting in 100% participation and agreement that this study was necessary, and the term INAA was agreed to be optimal. Three more statements were added based on the results and comments of the panel, resulting in a final 25 statements and nine reporting items. All 25 statements reached an agreement of ≥ 87%, and all nine reporting items reached an agreement of 100%. The Cronbach's alpha increased for each consecutive round (round 1 = .84, round 2 = .87, round 3 = .90, and round 4 = .92). Thus, consensus was reached for all statements and reporting items. CONCLUSION: This Delphi study established the first consensus document on INAA regarding terminology, definition, classification, diagnostic criteria, and algorithm, as well as reporting standards. The results of this study create essential conditions for scientific research on this disease. The presented consensus will need future amendments in accordance with newly acquired knowledge.

Predictive role of neutrophil-percentage-to-albumin, neutrophil-to-lymphocyte and eosinophil-to-lymphocyte ratios for mortality in patients with COPD: Evidence from NHANES 2011-2018.

BACKGROUND AND OBJECTIVE: This study evaluated the predictive roles of hematologic inflammatory biomarkers including neutrophil-percentage-to-albumin ratio (NPAR), neutrophil-to-lymphocyte ratio (NLR) and eosinophil-to-lymphocyte ratio (ELR) for mortality in community-dwelling individuals with chronic obstructive pulmonary disease (COPD). METHODS: This longitudinal study extracted data of adults 40-79 years who had physician-diagnosed COPD from the United States (US) National Health and Nutrition Examination Survey (NHANES) 1999-2018. Cox regressions determined the associations between NPAR, NLR, ELR and their components, with all-cause mortality, cardiovascular disease (CVD) mortality and mortality from chronic lower respiratory disease (CLRD). Receiver operating characteristic (ROC) curve analysis estimated the predictive performances of these biomarkers for 5-year all-cause mortality. RESULTS: Data of 1158 subjects were analysed. After adjustment, higher NPAR was significantly associated with increased all-cause and CVD mortality, and mortality from CLRD (adjusted hazard ratio [aHR] = 1.14, 1.15 and 1.16). Higher NLR was associated with an increased all-cause and CVD mortality (aHR = 1.16 and 1.29). Higher neutrophil was associated with increased all-cause mortality and mortality from CLRD (aHR = 1.13 and 1.34). Albumin was associated with decreased all-cause and CVD mortality (aHR = 0.91 and 0.86). ELR, eosinophil or lymphocyte was not significantly associated with either mortality outcomes. Adjusted AUC of NPAR and NLR in predicting 5-year all-cause mortality were 0.808 (95% CI: 0.722-0.845) and 0.799 (95% CI: 0.763-0.835), respectively. CONCLUSION: In community-dwelling US adults with COPD, increased NPAR and NLR are associated with mortality risks. NPAR outperforms the other hematologic inflammatory biomarkers in predicting 5-year all-cause mortality.

The COVIDTW study: Clinical predictors of COVID-19 mortality and a novel AI prognostic model using chest X-ray.

BACKGROUND: There is a lack of published research on the impact of the first wave of the COVID-19 pandemic in Taiwan. We investigated the mortality risk factors among critically ill patients with COVID-19 in Taiwan during the initial wave. Furthermore, we aim to develop a novel AI mortality prediction model using chest X-ray (CXR) alone. METHOD: We retrospectively reviewed the medical records of patients with COVID-19 at Taipei Tzu Chi Hospital from May 15 to July 15 2021. We enrolled adult patients who received invasive mechanical ventilation. The CXR images of each enrolled patient were divided into 4 categories (1st, pre-ETT, ETT, and WORST). To establish a prediction model, we used the MobilenetV3-Small model with "Imagenet" pretrained weights, followed by high Dropout regularization layers. We trained the model with these data with Five-Fold Cross-Validation to evaluate model performance. RESULT: A total of 64 patients were enrolled. The overall mortality rate was 45%. The median time from symptom onset to intubation was 8 days. Vasopressor use and a higher BRIXIA score on the WORST CXR were associated with an increased risk of mortality. The areas under the curve of the 1st, pre-ETT, ETT, and WORST CXRs by the AI model were 0.87, 0.92, 0.96, and 0.93 respectively. CONCLUSION: The mortality rate of COVID-19 patients who receive invasive mechanical ventilation was high. Septic shock and high BRIXIA score were clinical predictors of mortality. The novel AI mortality prediction model using CXR alone exhibited a high performance.

Survival of Four Conical Implant Abutment Connections After Removal of the Abutment Screw and Simulated Cyclic Loading: An In Vitro Comparative Study.

This in vitro study evaluated the mechanical behavior of different conical connection implant systems after abutment screw withdrawal. Four conical connection systems were selected based on different conical half-angles: Ankylos (5.7°), Cowell (7.0°), Straumann (7.5°), and Astra (11.0°). In each system, 5 implants and abutments were used (n = 5). According to the recommended value, each abutment screw was torqued to settle the abutment and then withdrawn through a predesigned hole of the cemented crown. The retentiveness of the abutment was evaluated by the following mechanical testing. All specimens were subjected to cyclic loading of 20-200 N, 30°, and 4-mm off-axis to the implant axis, for 106 cycles. The pullout forces and axial displacements of the abutments were measured. The data of the Cowell system was obtained from our previous work. All groups other than Astra group, in which abutment loosened after abutment screw withdrawal, passed the cyclic loading test. Straumann group demonstrated a significantly lower pullout force (27.4 ± 21.1 N) than Ankylos (160.1 ± 41.4 N) and Cowell (183.7 ± 30.5 N) groups. All groups showed abutment rebound after screw withdrawal except Straumann group. In addition, Ankylos, Cowell, and Straumann groups demonstrated axial displacement after cyclic loading. In terms of the retentiveness of the abutment after abutment screw withdrawal examined in this study, Ankylos and Cowell groups had much higher retentiveness than Straumann group, while Astra group had none. Conical angle could be a key design parameter to make abutment screw withdrawal after conical abutment settlement feasible, but more studies must be conducted for clinical application.

Pseudomonas aeruginosa Infections Are Associated with Infection Recurrence in Arteriovenous Grafts Treated with Revision.

Background and Objectives: This study was conducted to investigate whether Pseudomonas aeruginosa (PA) infections of arteriovenous grafts (AVGs) recur more frequently than other bacterial infections following treatment with revision. Materials and Methods: Operative procedures, including total excision, subtotal excision, and revision, were performed on 60 patients to treat 65 AVG infections. Final outcomes were classified as no infection recurrence, infection recurrence, and death without prior recurrence. In the competing risk setting, the cumulative incidence was estimated using the cumulative incidence function and Gray's test, and the associations between outcomes and different variables were estimated using a subdistribution hazard (SDH) model. Results: Comparing AVG infections with and without recurrence, PA infection was not associated with a higher risk of infection recurrence (p = 0.13); however, the first operative procedure type was associated with infection recurrence (p = 0.04). AVGs with PA infection were associated with a higher total number of surgical interventions (p < 0.05) than AVGs without PA infection. Regarding the cumulative incidences of outcomes, for AVGs treated with subtotal excision or revision, the cumulative incidence of recurrent infection was 3.3-fold higher for those with PA infection than without one year after the first surgery. However, when AVGs were treated with revision alone, the cumulative incidence was 4.1-fold. After excluding AVGs treated with total excision, the SDH model was applied, obtaining a hazard ratio for infection recurrence of 16.05 (p = 0.02) for AVGs with PA infection compared with AVGs without PA infection. No other variables were significantly associated with infection recurrence. Conclusions: For subtotal resection and revision, AVGs infected with PA had a higher recurrence rate than those infected with other species. However, revision surgery may aggravate the recurrence rate.

Higher pre-treatment skin sympathetic nerve activity and elevated resting heart rate after chemoradiotherapy predict worse esophageal cancer outcomes.

BACKGROUND: Chemoradiotherapy (CRT), which might affect the autonomic system, is the mainstay therapy for advanced esophageal squamous cell carcinoma (ESCC). Autonomic dysfunction has been found to possibly lead to cancer mortality in those with elevated resting heart rates (RHR). Skin sympathetic nerve activity (SKNA) is a new method of stimulating electrical signals in skin to evaluate autonomic function from sympathetic tone. In this study, we investigated the association between changes in RHR and autonomic function and ESCC mortality. METHODS: Thirty-nine stage II-IV ESCC patients receiving CRT between March 2019 and November 2020 were prospectively enrolled and carefully selected, followed up and received the same meticulous supportive care. Serial RHR was recorded every two weeks from before CRT to eight weeks after CRT and average SKNA were recorded before and four weeks after CRT. All-cause mortality was defined as primary outcome. RESULTS: We found the RHR of ESCC patients to be significantly elevated and peaking at four weeks after CRT (p < 0.001) and then to gradually decrease. Those with an elevated RHR above the cutoff level (18 beat-per-minute) at eight weeks after CRT had worse overall survival. In addition, those with higher baseline sympathetic tone (average SKNA ≥ 0.86 µV) also had poor outcome. CONCLUSIONS: Increased pre-treatment sympathetic tone and elevated RHR after CRT are alarm signs of poor ESCC outcome. Further exploration of the mechanisms underlying these associations could potentially lead to intervention strategies for reducing mortality. TRIAL REGISTRATION: This study is registered with ClinicalTrials.gov, identifier: NCT03243448.

Deep Learning-based Artificial Intelligence Improves Accuracy of Error-prone Lung Nodules.

Introduction: Early detection of lung cancer is one way to improve outcomes. Improving the detection of nodules on chest CT scans is important. Previous artificial intelligence (AI) modules show rapid advantages, which improves the performance of detecting lung nodules in some datasets. However, they have a high false-positive (FP) rate. Its effectiveness in clinical practice has not yet been fully proven. We aimed to use AI assistance in CT scans to decrease FP. Materials and methods: CT images of 60 patients were obtained. Five senior doctors who were blinded to these cases participated in this study for the detection of lung nodules. Two doctors performed manual detection and labeling of lung nodules without AI assistance. Another three doctors used AI assistance to detect and label lung nodules before manual interpretation. The AI program is based on a deep learning framework. Results: In total, 266 nodules were identified. For doctors without AI assistance, the FP was 0.617-0.650/scan and the sensitivity was 59.2-67.0%. For doctors with AI assistance, the FP was 0.067 to 0.2/scan and the sensitivity was 59.2-77.3% This AI-assisted program significantly reduced FP. The error-prone characteristics of lung nodules were central locations, ground-glass appearances, and small sizes. The AI-assisted program improved the detection of error-prone nodules. Conclusions: Detection of lung nodules is important for lung cancer treatment. When facing a large number of CT scans, error-prone nodules are a great challenge for doctors. The AI-assisted program improved the performance of detecting lung nodules, especially for error-prone nodules.

Transcriptome analysis in patients with asthma after inhaled combination therapy with long-acting ß2-agonists and corticosteroids.

Introduction: Asthma is one of the major public health problems that imposes a great burden on societal, financial, and healthcare around the world. Asthma poorly affects the health-related quality of life and daily activities of patients. Treatment of asthma, including inhaled corticosteroids (ICS) and long-acting beta-agonists (LABAs), mainly aims to improve the lung function and reduce symptoms and exacerbations. Current treatment regimens are symptom-based strategies, and the status of airway inflammation after treatment is yet unknown. We conducted this study to understand the comprehensive inflammation or airway remodeling status of patients after ICS-LABA treatment through RNA transcriptome analysis. Materials and methods: Eight newly diagnosed asthmatic patients and two healthy subjects were recruited in this study. Asthmatic patients underwent blood tests, lung function test, and RNA transcriptome analysis before and after ICS-LABA treatment. Results: In comparison with healthy subjects, pretreatment asthmatic patients had higher expression of protein tyrosine kinase and related signaling pathways. After ICS-LABA treatment, the expression of nuclear receptor transcription coactivator, N-acetyltransferase, protein tyrosine kinase, nuclear receptor, and RNA polymerase II-activating transcription factor were downregulated. However, the post-treatment asthmatic patients still had higher expression of cysteine-type endopeptidase, endodeoxyribonuclease, apolipoprotein, and unfolded protein was still upregulated than healthy subjects. Conclusions: The combination of ICS/LABAs decreased airway inflammatory and remodeling pathways. However, allergen stimulation-related pathways were still upregulated in patients after ICS/LABA treatment. The combination of medication and allergen removal is a complete strategy for asthma.

Molecular Characteristics and Distribution of Virulence Genes among Staphylococcus aureus Complex Isolates Derived from Vascular Access Infections.

Staphylococcus aureus is a major human pathogen that produces various virulence factors which promote the binding of bacteria to tissues and medical devices such as vascular access devices, thereby developing a wide range of invasive infections. Vascular access serves as an entry site for S. aureus and elevates the risk of infection in the hemodialysis population. Nevertheless, the distribution of virulence genes in Staphylococcus spp. associated with vascular access infections (VAIs) has not been studied previously. In this study, we determined the relationship between the molecular characteristics and virulence profiles of S. aureus isolates obtained from VAIs. We collected isolates from patients with VAIs between August 2017 and December 2020 and further analyzed the molecular characteristics, antimicrobial resistance profiles, and virulence gene distribution in the isolates. Overall, 15 sequence types (STs), including a new ST (ST6892) and 19 spa types, were identified among the 56 isolates. Of the 53 S. aureus isolates, ST8, ST239, ST45, and ST59 were the predominant STs, whereas ST2250 was the only ST in 3 S. argenteus isolates. ST45-SCCmecIV-t026 (abbreviated as ST45-IV-t026), ST59-V-t437, and ST8-IV-t008 were the predominant clones that belonged to agr type I. All isolates harbored clfB and eno, whereas all S. aureus isolates harbored clfA. In addition, 10 Panton-Valentine leucocidin-positive isolates belonged to ST8 and ST59, with ST8-IV-t008 and ST59-V-t437 being the predominant clones. In brief, the distribution of virulence genes associated with STs may assist in the spread of molecular types of Staphylococcus spp.

The BUILT study: a single-center 5-year experience of Lung Cancer screening in Taiwan.

Background: There are no uniform guidelines on low-dose computed tomography (LDCT) follow-up in lung cancer screening. Few studies have analyzed the incidental abnormalities and role of tumor markers in lung cancer screening. The purpose of this study was to investigate the diagnostic performance of LDCT, optimal follow-up duration, incidental findings, and role of tumor markers in diagnosing lung cancer. Methods: We retrospectively analyzed subjects who underwent their first LDCT in Taipei Tzu Chi Hospital between September 1, 2015, and August 31, 2016. All chest CT scans until August 31, 2020, were recorded. A non-calcified nodule with a diameter ≥2 mm on LDCT was defined as a positive result. We extracted the data, including possible risk factors of lung cancer and follow-up outcomes. Results: A total of 1502 subjects were recruited. Of the 38 subjects who underwent biopsy, 31 had confirmed lung cancer. Lung cancer in all patients was diagnosed within 4 years. Univariate logistic regression analysis revealed that a family history of lung cancer in first-degree relatives and abnormal serum carcinoembryonic antigen (CEA) levels were the significant risk factors for lung cancer. A cumulative lung cancer incidence of 54.7 patients per 1000 person-years was determined solely via radiological follow-up. In total, 271 (18%) subjects exhibited incidental findings on baseline LDCT. Conclusion: The overall lung cancer detection rate in this study was 2.1% in the 5-year study period. A family history of lung cancer and abnormal serum CEA levels are important risk factors for lung cancer. A minimum of 4-year follow-up is required to track suspicious nodules. A purely radiological follow-up detects a high incidence of lung cancer.

The Worsening of Positional Mild Obstructive Sleep Apnea over Time Is Associated with an Increase in Body Weight: Impact on Blood Pressure and Autonomic Nervous System.

BACKGROUND: Most patients with mild obstructive sleep apnea (OSA) are positional dependent. Although mild OSA worsens over time, no study has assessed the natural course of positional mild OSA. OBJECTIVES: The aim of this study was to evaluate the natural course of positional mild OSA, its most valuable progression predictor, and its impact on blood pressure (BP) and the autonomic nervous system (ANS). METHODS: This retrospective observational cohort study enrolled 86 patients with positional mild OSA and 26 patients with nonpositional mild OSA, with a follow-up duration of 32.0 ± 27.6 months and 37.6 ± 27.8 months, respectively. Polysomnographic variables, BP, and ANS functions were compared between groups at baseline and after follow-up. RESULTS: In patients with positional mild OSA after follow-up, the apnea/hypopnea index (AHI) increased (9.1 ± 3.3/h vs. 22.0 ± 13.2/h, p = 0.000), as did the morning systolic BP (126.4 ± 13.3 mm Hg vs. 130.4 ± 15.9 mm Hg, p = 0.011), and the sympathetic activity (49.4 ± 12.3% vs. 55.3 ± 13.1%, p = 0.000), while the parasympathetic activity decreased (50.6 ± 12.3% vs. 44.7 ± 13.1%, p = 0.000). The body mass index changes were the most important factor associated with AHI changes among patients with positional mild OSA (Beta = 0.259, adjust R2 = 0.056, p = 0.016, 95% confidence interval 0.425 and 3.990). The positional dependency disappeared over time in 66.3% of patients with positional mild OSA while 69.2% of patients with nonpositional mild OSA retained nonpositional. CONCLUSIONS: In patients with positional mild OSA, disease severity, BP, and ANS regulation worse over time. Increased weight was the best predictor for its progression and the loss of positional dependency. Better treatments addressing weight control and consistent follow-up are needed for positional mild OSA.

The COPD-readmission (CORE) score: A novel prediction model for one-year chronic obstructive pulmonary disease readmissions.

BACKGROUND: Acute exacerbation of chronic obstructive pulmonary disease (COPD) results in deterioration of lung function and mortality. Previous prediction models have been designed for severe exacerbation of COPD, leading to readmission. However, these models lacked newly established predictors such as the eosinophil count. The present study developed a novel CO PD-re admission (CORE) score. METHODS: We retrospectively reviewed medical records of patients visiting Taipei Tzu Chi Hospital between January 1, 2014, and May 31, 2017. We analyzed all covariates by univariate and then multivariate logistic regressions. Numeric or ordinal variables showing statistical significance were transformed into dichotomous variables by cut-off values determined by the Youden Index. The CORE score was designed to predict one-year readmission rates. RESULTS: A total of 625 patients were recruited. After analysis, the CORE score included five predictors (eosinophil count, lung function, triple inhaler therapy, previous hospitalization, and neuromuscular disease). We observed a highly linear relationship between the CORE score and COPD readmission (R = 0.981; R 2 = 0.963; P < 0.001). The CORE score had a higher predictive accuracy than that for hospitalization in the previous year (area under the curve = 0.703 vs. 0.619; P < 0.001). Patients with higher CORE scores had a shorter time to first COPD readmission (P < 0.001). Using the zero point as a reference, the hazard ratios for each score from 1 to 4 were 1.209, 2.211, 3.359, and 4.510, respectively. CONCLUSION: The CORE score includes two novel predictors (eosinophil count and triple inhaler therapy). The model has a high predictive power for one-year COPD readmission.

Clinicopathological features and outcome of esophageal neuroendocrine tumor: A retrospective multicenter survey by the digestive endoscopy society of Taiwan.

BACKGROUND & AIMS: Esophageal neuroendocrine tumors (NET) are very rare and mostly carcinomic, carrying poor prognosis. There is still no guideline or consensus on the treatment for esophageal NET. METHODS: Patients with histologically-proven esophageal neuroendocrine tumor were recruited from 9 hospitals in Taiwan between 2002 and 2017. Clinical, laboratory, radiological, endoscopic, pathological data, treatment strategies, follow-up periods, and survivals were collected retrospectively. RESULTS: In total, 39 esophageal NET were analyzed and 38 were neuroendocrine carcinoma (NEC). Sixteen (41%) patients had mixed components with either adenocarcinoma (N = 9, 23%) or squamous-cell carcinoma (SCC) (N = 7, 18%). 64.1% of the patients experienced dysphagia and ulcerative mass was the most comment endoscopic finding. There was a higher proportion of drinkers (54.1%), betel chewers (21.6%) and smokers (64.9%) among the patients than in the general population in Taiwan. Five patients (12.8%) had been diagnosed with other cancers. Definite chemoradiotherapy (N = 14, 35.9%) and surgery (N = 7, 17.9%) were the major treatment. Patients with Ki-67% above the median level (50%) in the tumors tended to have worse survival (P = 0.06). However, presence of mixed component was not a significant survival predictor in our study (P = 0.56). CONCLUSION: Mixed component of an esophageal NET is commonly observed. Staged workup and the principle of treatment can follow that for the common cancer type of esophagus. The risk factors and behaviors of esophageal NEC in Taiwan seem to be similar to that of esophageal SCC.