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Data curation for a hospital-based cancer registry heavily relies on the labor-intensive manual abstraction process by cancer registrars to identify cancer-related information from free-text electronic health records. To streamline this process, a natural language processing system incorporating a hybrid of deep learning-based and rule-based approaches for identifying lung cancer registry-related concepts, along with a symbolic expert system that generates registry coding based on weighted rules, was developed. The system is integrated with the hospital information system at a medical center to provide cancer registrars with a patient journey visualization platform. The embedded system offers a comprehensive view of patient reports annotated with significant registry concepts to facilitate the manual coding process and elevate overall quality. Extensive evaluations, including comparisons with state-of-the-art methods, were conducted using a lung cancer dataset comprising 1428 patients from the medical center. The experimental results illustrate the effectiveness of the developed system, consistently achieving F1-scores of 0.85 and 1.00 across 30 coding items. Registrar feedback highlights the system’s reliability as a tool for assisting and auditing the abstraction. By presenting key registry items along the timeline of a patient’s reports with accurate code predictions, the system improves the quality of registrar outcomes and reduces the labor resources and time required for data abstraction. Our study highlights advancements in cancer registry coding practices, demonstrating that the proposed hybrid weighted neural-symbolic cancer registry system is reliable and efficient for assisting cancer registrars in the coding workflow and contributing to clinical outcomes.

Abstract Combining epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) with an anti‐ vascular endothelial growth factor (VEGF) agent, bevacizumab or ramucirumab, is indicated for advanced lung adenocarcinoma harboring EGFR mutation. This study aimed to show the real‐world data of combination therapy and compare the effectiveness between bevacizumab and ramucirumab in combination with an EGFR‐TKI. This retrospective study enrolled 47 patients diagnosed of stage IV lung adenocarcinoma with exon 19 deletion or L858R point mutation, receiving a first‐line EGFR‐TKI with anti‐VEGF agent, including 34 (72%) and 13 (28%) patients receiving bevacizumab and ramucirumab, respectively. The response rate was similar in both groups (p = 0.38). Patients receiving bevacizumab had similar progression free survival (PFS) as those receiving ramucirumab (median PFS: 21.9 vs. 24.2 months, p = 0.4871); similar finding was noted in overall survival (OS) (median OS: 33.5 months vs. not reached, p = 0.4618). Patients receiving ramucirumab experienced a significantly high‐grade hypertension compared to those receiving bevacizumab (p = 0.0351). Multivariable Cox regression analysis found independent risk factors for worse PFS included poorer ECOG performance status, multiple (≥3) metastatic sites, brain metastasis, and pleural metastasis/effusion, while the type of anti‐VEGF agent was not a risk factor. Pericardial metastasis/effusion was the only one independent risk factor for worse OS. In summary, ramucirumab may have similar effectiveness as bevacizumab in combination with an EGFR‐TKI as first line therapy for advanced lung adenocarcinoma harboring susceptible EGFR mutation. Further large‐scale registry‐based cohort studies may be needed to validate our findings.

Abstract 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.

BackgroundInternational Classification of Diseases codes are widely used to describe diagnosis information, but manual coding relies heavily on human interpretation, which can be expensive, time consuming, and prone to errors. With the transition from the International Classification of Diseases, Ninth Revision, to the International Classification of Diseases, Tenth Revision (ICD-10), the coding process has become more complex, highlighting the need for automated approaches to enhance coding efficiency and accuracy. Inaccurate coding can result in substantial financial losses for hospitals, and a precise assessment of outcomes generated by a natural language processing (NLP)–driven autocoding system thus assumes a critical role in safeguarding the accuracy of the Taiwan diagnosis related groups (Tw-DRGs). ObjectiveThis study aims to evaluate the feasibility of applying an International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM), autocoding system that can automatically determine diagnoses and codes based on free-text discharge summaries to facilitate the assessment of Tw-DRGs, specifically principal diagnosis and major diagnostic categories (MDCs). MethodsBy using the patient discharge summaries from Kaohsiung Medical University Chung-Ho Memorial Hospital (KMUCHH) from April 2019 to December 2020 as a reference data set we developed artificial intelligence (AI)–assisted ICD-10-CM coding systems based on deep learning models. We constructed a web-based user interface for the AI-assisted coding system and deployed the system to the workflow of the certified coding specialists (CCSs) of KMUCHH. The data used for the assessment of Tw-DRGs were manually curated by a CCS with the principal diagnosis and MDC was determined from discharge summaries collected at KMUCHH from February 2023 to April 2023. ResultsBoth the reference data set and real hospital data were used to assess performance in determining ICD-10-CM coding, principal diagnosis, and MDC for Tw-DRGs. Among all methods, the GPT-2 (OpenAI)-based model achieved the highest F1-score, 0.667 (F1-score 0.851 for the top 50 codes), on the KMUCHH test set and a slightly lower F1-score, 0.621, in real hospital data. Cohen κ evaluation for the agreement of MDC between the models and the CCS revealed that the overall average κ value for GPT-2 (κ=0.714) was approximately 12.2 percentage points higher than that of the hierarchy attention network (κ=0.592). GPT-2 demonstrated superior agreement with the CCS across 6 categories of MDC, with an average κ value of approximately 0.869 (SD 0.033), underscoring the effectiveness of the developed AI-assisted coding system in supporting the work of CCSs. ConclusionsAn NLP-driven AI-assisted coding system can assist CCSs in ICD-10-CM coding by offering coding references via a user interface, demonstrating the potential to reduce the manual workload and expedite Tw-DRG assessment. Consistency in performance affirmed the effectiveness of the system in supporting CCSs in ICD-10-CM coding and the judgment of Tw-DRGs.

BackgroundTo date, studies investigating the association between pre-biologic biomarker levels and post-biologic outcomes have been limited to single biomarkers and assessment of biologic efficacy from structured clinical trials.AimTo elucidate the associations of pre-biologic individual biomarker levels or their combinations with pre-to-post biologic changes in asthma outcomes in real-life.MethodsThis was a registry-based, cohort study using data from 23 countries, which shared data with the International Severe Asthma Registry (May 2017-February 2023). The investigated biomarkers (highest pre-biologic levels) were immunoglobulin E (IgE), blood eosinophil count (BEC) and fractional exhaled nitric oxide (FeNO). Pre- to approximately 12-month post-biologic change for each of three asthma outcome domains (i.e. exacerbation rate, symptom control and lung function), and the association of this change with pre-biologic biomarkers was investigated for individual and combined biomarkers.ResultsOverall, 3751 patients initiated biologics and were included in the analysis. No association was found between pre-biologic BEC and pre-to-post biologic change in exacerbation rate for any biologic class. However, higher pre-biologic BEC and FeNO were both associated with greater post-biologic improvement in FEV1 for both anti-IgE and anti-IL5/5R, with a trend for anti-IL4Rα. Mean FEV1 improved by 27-178 mL post-anti-IgE as pre-biologic BEC increased (250 to 1000 cells/µL), and by 43-216 mL and 129-250 mL post-anti-IL5/5R and -anti-IL4Rα, respectively along the same BEC gradient. Corresponding improvements along a FeNO gradient (25-100 ppb) were 41-274 mL, 69-207 mL and 148-224 mL for anti-IgE, anti-IL5/5R, and anti-IL4Rα, respectively. Higher baseline BEC was also associated with lower probability of uncontrolled asthma (OR 0.392; p=0.001) post-biologic for anti-IL5/5R. Pre-biologic IgE was a poor predictor of subsequent pre-to-post-biologic change for all outcomes assessed for all biologics. The combination of BEC + FeNO marginally improved the prediction of post-biologic FEV1 increase (adjusted R2: 0.751), compared to BEC (adjusted R2: 0.747) or FeNO alone (adjusted R2: 0.743) (p=0.005 and

Background: Malposition may occur during peripherally inserted central catheter insertion. Accurately measuring the length of a peripherally inserted central catheter is crucial to preventing malposition, including “long peripherally inserted central catheter placement,” in which the tip of a peripherally inserted central catheter is deeper than the target position. The traditional method of measuring peripherally inserted central catheter length involves measuring from the insertion site to the parasternal notch and down to the third or fourth intercostal space, which may result in overestimation because of the thickness of the pectoralis major and anterior chest wall. To avoid this overestimation, the authors developed and tested a modified method for reducing long peripherally inserted central catheter placement. Methods: This study employed a retrospective design. Chest X-rays were used to examine the peripherally inserted central catheter tip positions in 48 patients in the medical intensive care unit who had undergone peripherally inserted central catheter insertion. The traditional and modified measurement methods were used to measure the peripherally inserted central catheter length in 17 and 31 patients, respectively. Fisher’s exact test was used to examine between-group differences in the incidence of different types of peripherally inserted central catheter malposition. Results: The peripherally inserted central catheter tip position was near the target position in five patients (29.41%) in the traditional measurement group and 17 patients (54.84%) in the modified measurement group ( p = 0.132), whereas long peripherally inserted central catheter placement occurred in six patients (35.29%) in the traditional measurement group and one patient (3.23%) in the modified measurement group ( p = 0.006). However, the incidence of other types of peripherally inserted central catheter malposition did not differ significantly between the groups. Conclusions: The results of this study that the proposed modified measurement method may be able to reduce the incidence of long peripherally inserted central catheter placement among medical intensive care unit patients. The method must be further evaluated in prospective studies and studies with larger sample sizes in the future.

Background/Purpose: The Accreditation Council for Graduate Medical Education (ACGME) milestones have been implemented in residency training worldwide. We investigated the development of individual competency in first-year residents (R1) and second-year postgraduate students (PGY2) who received internal medicine training in Taiwan. Methods: A multicenter observational cohort study was conducted to evaluate the competency-based milestone evaluation designed by the Taiwan Society of Internal Medicine in 2019. The evaluation was based on the ACGME-accredited milestone ratings. Periodic evaluation of milestone achievements of R1 and PGY2, who entered the internal medicine residency training at six medical centers, was performed. Each resident was evaluated every 3 months. Results: Among the 98 R1 enrolled in 2019, substantial improvement in sub-competencies, including skill in performing procedures (Patient Care 4), clinical knowledge (Medical Knowledge 1), knowledge of diagnostic testing and procedures (Medical Knowledge 2), and identify impact the cost of health care and practices cost-effective care (Systems Based Practice 3) during the two years of training. Among the 107 R1 and 46 PGY2 enrolled in 2020, no significant difference in baseline milestone ratings was observed. However, the milestone assessments of R1 in 2020 showed improvement in nearly all sub-competencies compared with the stationary status of PGY2 in 2020. Conclusion: We demonstrate the application of ACGME-based accredited milestone ratings to target the educational goals of internal medicine residency training in Taiwan. Differences in milestone ratings between different PGY training systems exist. The long-term impact of performance among different PGY training systems requires further investigation.

Abstract Lung squamous cell carcinoma (LUSC) represents a minor proportion of nonsmall cell lung cancer (NSCLC) harboring a poor prognosis. Herein, retrospective medical record research was performed to investigate real‐world treatment patterns and identify the prognostic factors among LUSC patients. A total of 173 patients with a median age of 68 years were enrolled for analysis. Males were predominant (n = 143, 83%) and current or ex‐smokers contributed to 78% of the entire cohort. Pleura and lung were the most common metastatic sites, whereas brain metastasis was only 7%. After diagnosis, however, only 107 patients (62%) had received first‐line chemotherapy. In the chemotherapy cohort, median progression‐free survival (PFS) and overall survival (OS) were 3.9 and 11.1 months, respectively. After multivariable analysis, bone metastasis and the use of first‐line single‐agent chemotherapy independently predicted shorter PFS. For baseline characteristics, male sex, metastasis to lung, pleura, liver, and bone independently predicted worse OS. Regarding the treatment pattern, patients who had undergone standard first‐line doublet therapy and employed targeted therapies after disease progression linked to longer OS. In the real world, even those who underwent chemotherapy still had poor outcome. The findings may help clinicians to orchestrate the treatment strategies for LUSC patients and provide further direction of large‐scale studies.

Summary: The ability to detect cancer at an early stage in patients who would benefit from effective therapy is a key factor in increasing survivability. This work proposes an evolutionary supervised learning method called CancerSig to identify cancer stage-specific microRNA (miRNA) signatures for early cancer predictions. CancerSig established a compact panel of miRNA signatures as potential markers from 4,667 patients with 15 different types of cancers for the cancer stage prediction, and achieved a mean performance: 10-fold cross-validation accuracy, sensitivity, specificity, and area under the receiver operating characteristic curve of 84.27% ± 6.31%, 0.81 ± 0.12, 0.80 ± 0.10, and 0.80 ± 0.06, respectively. The pan-cancer analysis of miRNA signatures suggested that three miRNAs, hsa-let-7i-3p, hsa-miR-362-3p, and hsa-miR-3651, contributed significantly toward stage prediction across 8 cancers, and each of the 67 miRNAs of the panel was a biomarker of stage prediction in more than one cancer. CancerSig may serve as the basis for cancer screening and therapeutic selection..

Abstract Gefitinib and erlotinib are the first-line tyrosine kinase inhibitors (TKI) for advanced non-small-cell lung cancer. However, co-administration of either drug with proton pump inhibitors (PPI) or histamine-2 receptor antagonists (H2RA) may reduce TKI’s bioavailability. Therefore, we aimed to investigate the effects of these drug–drug interactions. We surveyed nationwide population-based databases between Jan 1, 2010, and Dec 30, 2018. Newly diagnosed patients with advanced lung adenocarcinoma who received first-line gefitinib or erlotinib were identified. Effects on overall survival (OS) and time to next treatment (TTNT) association between PPIs or H2RAs and co-administrated gefitinib or erlotinib were evaluated. PPIs or H2RAs users were defined if the period overlapped with TKIs by ≥ 20%. A total of 4340 gefitinib and 1635 erlotinib users were included. PPI group had the shortest median OS and TTNT compared to the H2RA and non-user groups (in gefitinib cohort: OS: 14.35 vs. 17.67 vs. 21.87 months; P

Abstract Bladder urothelial carcinoma (BLC) is one of the most common cancers in men, and its heterogeneity challenges the treatment to cure this disease. Recently, microRNAs (miRNAs) gained promising attention as biomarkers due to their potential roles in cancer biology. Identifying survival-associated miRNAs may help identify targets for therapeutic interventions in BLC. This work aims to identify a miRNA signature that could estimate the survival in patients with BLC. We developed a survival estimation method called BLC-SVR based on support vector regression incorporated with an optimal feature selection algorithm to select a robust set of miRNAs as a signature to estimate the survival in patients with BLC. BLC-SVR identified a miRNA signature consisting of 29 miRNAs and obtained a mean squared correlation coefficient and mean absolute error of 0.79 ± 0.02 and 0.52 ± 0.32 year between actual and estimated survival times, respectively. The prediction performance of BLC-SVR had a better estimation capability than other standard regression methods. In the identified miRNA signature, 14 miRNAs, hsa-miR-432-5p, hsa-let-7e-3p, hsa-miR-652-3p, hsa-miR-629-5p, and hsa-miR-203a-3p, hsa-miR-129-5p, hsa-miR-769-3p, hsa-miR-570-3p, hsa-miR-320c, hsa-miR-642a-5p, hsa-miR-496, hsa-miR-5480-3p, hsa-miR-221-5p, and hsa-miR-7-1-3p, were found to be good biomarkers for BLC diagnosis; and the six miRNAs, hsa-miR-652-5p, hsa-miR-193b-5p, hsa-miR-129-5p, hsa-miR-143-5p, hsa-miR-496, and hsa-miR-7-1-3p, were found to be good biomarkers of prognosis. Further bioinformatics analysis of this miRNA signature demonstrated its importance in various biological pathways and gene ontology annotation. The identified miRNA signature would further help in understanding of BLC diagnosis and prognosis in the development of novel miRNA-target based therapeutics in BLC.

Identifying a miRNA signature associated with survival will open a new window for developing miRNA-targeted treatment strategies in stomach and esophageal cancers (STEC). Here, using data from The Cancer Genome Atlas on 516 patients with STEC, we developed a Genetic Algorithm-based Survival Estimation method, GASE, to identify a miRNA signature that could estimate survival in patients with STEC. GASE identified 27 miRNAs as a survival miRNA signature and estimated the survival time with a mean squared correlation coefficient of 0.80 ± 0.01 and a mean absolute error of 0.44 ± 0.25 years between actual and estimated survival times, and showed a good estimation capability on an independent test cohort. The miRNAs of the signature were prioritized and analyzed to explore their roles in STEC. The diagnostic ability of the identified miRNA signature was analyzed, and identified some critical miRNAs in STEC. Further, miRNA-gene target enrichment analysis revealed the involvement of these miRNAs in various pathways, including the somatotrophic axis in mammals that involves the growth hormone and transforming growth factor beta signaling pathways, and gene ontology annotations. The identified miRNA signature provides evidence for survival-related miRNAs and their involvement in STEC, which would aid in developing miRNA-target based therapeutics.

Background/purpose: Three first-line epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are widely available to treat advanced lung adenocarcinoma harboring EGFR mutation. However, studies comparing efficacy or effectiveness of these EGFR TKIs came out with inconclusive results. Methods: In this real-world data analysis with a nationwide retrospective cohort design, adult patients with newly diagnosed advanced lung adenocarcinoma with EGFR mutation between 2011 and 2016, who received a first-line EGFR TKI, were included. Overall survival (OS) and time to next treatment (TTNT) were compared between patients receiving different EGFR TKIs after overlap weighting. Results: We enrolled 10,431 patients, including 6,230, 2,359, and 1842 in gefitinib, erlotinib, and afatinib groups, respectively. The median (95% confidence interval [CI]) OS were 24.2 (22.9–26.2), 25.7 (24.0–27.9), and 29.1 (25.8–32.1) months for those receiving gefitinib, erlotinib, and afatinib, respectively (p = 0.001). The hazard ratios (95% CI) for the afatinib group were 0.85 (0.74–0.98) and 0.91 (0.79–1.05) comparing with the gefitinib and erlotinib groups, respectively. The median (95% CI) TTNT were 10.9 (10.4–11.2), 11.7 (11.3–12.1), 13.4 (12.5–14.3) months for those receiving gefitinib, erlotinib, and afatinib, respectively (p

Abstract Background In adults with primary spontaneous pneumothorax (PSP), contralateral recurrence occurs in about 25–28% when there are asymptomatic blebs. How to treat contralateral recurrence of PSP in pediatric populations remains controversial. This study evaluated the outcomes of excising contralateral blebs to prevent recurrence in adolescents being operated on for PSP under the same anesthesia. Methods One hundred thirty-two male PSP patients under age 19 were surgically treated in a single institution between January 2008 and December 2016. Thoracoscopic blebectomies with pleurodesis were performed in all patients. The patients were categorized into those with contralateral blebs receiving one-stage bilateral surgeries (32 patients), those with contralateral blebs only receiving unilateral surgeries (40 patients), and those without contralateral blebs only receiving unilateral surgeries (60 patients). Perioperative details and outcomes were retrospectively analyzed. Results Significant differences in contralateral recurrence rate were found among the three groups (0%, 30%, and 1%, respectively; P

Summary: We describe a protocol to identify physicochemical properties using amino acid sequences of spike (S) proteins of SARS-CoV-2. We present an S protein prediction technique named SPIKES, incorporating an inheritable bi-objective combinatorial genetic algorithm to determine the host species specificity. This protocol addresses the S protein amino acid sequence data collection, preprocessing, methodology, and analysis.For complete details on the use and execution of this protocol, please refer to Yerukala Sathipati et al. (2022). : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

Abstract Background Afatinib has shown favorable response rates (RRs) and longer progression free survival (PFS) in lung cancer patients harboring EGFR mutations compared with standard platinum-based chemotherapy. However, serious adverse drug reactions (ADRs) limit the clinical application of afatinib. Methods We designed a retrospective study, enrolling all patients with metastatic lung adenocarcinoma who were diagnosed and treated with 30 or 40 mg daily afatinib as their initial treatment in three Kaohsiung Medical University-affiliated hospitals in Taiwan. Results A total of 179 patients were enrolled in the study, of which 102 (57%) and 77 (43%) received 30 mg and 40 mg afatinib daily as their initial treatment, respectively. The patients initially using 30 mg afatinib daily had a similar RR (75% vs. 83%, p = 0.1672), median PFS (14.5 vs. 14.8 months, log-rank p = 0.4649), and median OS (34.0 vs. 25.2 months, log-rank p = 0.5982) compared with those initially using 40 mg afatinib daily. Patients initially receiving 30 mg afatinib daily had fewer ADRs compared with those using 40 mg daily. The overall incidence of moderate and severe ADRs was significantly lower in patients receiving 30 mg afatinib daily compared with those using 40 mg daily (49% vs. 77%, p = 0.002); similar findings was observed in terms of severe ADRs (7% vs. 24%, p

Abstract The association between sleep apnea (SA) and depression had been reported in a few previous studies. However, whether SA increases the risk of major depressive disorder (MDD) has not been studied comprehensively in a large-scale study. We performed this population-based cohort study to assess the association between SA and MDD. We identified adult patients having SA from the Taiwan National Health Insurance Research Database and excluded those having MDD before SA diagnosis. Thirty control subjects were randomly selected to match to each SA patient by age and sex. Totally, 10,259 SA patients were matched to 102,590 control subjects. The incidence rate and cumulative incidence of MDD were significantly higher in SA patients than in the control subjects (both p

Abstract The World Health Organization announced the coronavirus disease 2019 (COVID‐19) outbreak a pandemic on 12 March 2020. Although being in proximity to China, the original epicenter of the COVID‐19 outbreak, Taiwan has maintained a low number of COVID‐19 cases despite its close social ties and heavy traffic between Taiwan and China. Containment strategies executed by the Taiwanese government have attracted global attention. Similarly, in‐hospital settings, high alertness and swift responses to the changing outbreak situation are necessary to ensure hospital staff members' safety so they can continue to save patients' lives. Herein, we present infection control measures that can be adopted in hospital settings that were executed in a Taiwanese hospital to confront the COVID‐19 pandemic, including emergency preparedness and responses from the hospital administration, education, surveillance, patient flow arrangement, the partition of hospital zones, and the prevention of a systemic shutdown by using the “divided cabin, divided flow” strategy. The measures implemented by a Taiwan hospital during the COVID‐19 pandemic may not be universally applicable in every hospital. Nonetheless, the presented infection control methods have been practically executed and can be referenced or modified to fit each hospital's unique condition.

Abstract Background Corticosteroid treatment has been widely used in the treatment of septic shock, influenza, and ARDS, although some previous studies discourage its use in severe influenza patients. This multicenter retrospective cohort study conducted in the intensive care units (ICUs) of eight medical centers across Taiwan aims to determine the real-world status of corticosteroid treatment in patients with influenza-associated acute respiratory distress syndrome (ARDS) and its impact on clinical outcomes. Between October 2015 and March 2016, consecutive ICU patients with virology-proven influenza infections who fulfilled ARDS and received invasive mechanical ventilation were enrolled. The impact of early corticosteroid treatment (≥ 200 mg hydrocortisone equivalent dose within 3 days after ICU admission, determined by a sensitivity analysis) on hospital mortality (the primary outcome) was assessed by multivariable logistic regression analysis, and further confirmed in a propensity score-matched cohort. Results Among the 241 patients with influenza-associated ARDS, 85 (35.3%) patients receiving early corticosteroid treatment had similar baseline characteristics, but a significantly higher hospital mortality rate than those without early corticosteroid treatment [43.5% (37/85) vs. 19.2% (30/156), p

Objectives This study was conducted to explore the association between pneumoconiosis and pneumothorax.Design Retrospective cohort study.Setting Nationwide population-based study using the Taiwan National Health Insurance Database.Participants A total of 2333 pneumoconiosis patients were identified (1935 patients for propensity score (PS)-matched cohort) and matched to 23 330 control subjects by age and sex (7740 subjects for PS-matched cohort).Primary and secondary outcome measures The incidence and the cumulative incidence of pneumothorax.Results Both incidence and the cumulative incidence of pneumothorax were significantly higher in the pneumoconiosis patients as compared with the control subjects (p

Background: Patients with severe influenza-related acute respiratory distress syndrome (ARDS) have high morbidity and mortality. Moreover, nosocomial lower respiratory tract infection (NLRTI) complicates their clinical management and possibly worsens their outcomes. This study aimed to explore the clinical features and impact of NLRTI in patients with severe influenza-related ARDS. Methods: This was an institutional review board approved, retrospective, observational study conducted in eight medical centers in Taiwan. From January 1 to March 31 in 2016, subjects were enrolled from intensive care units (ICUs) with virology-proven influenza pneumonia, while all of those patients with ARDS requiring invasive mechanical ventilation and without bacterial community-acquired pneumonia (CAP) were analyzed. Baseline characteristics, critical-illness data and clinical outcomes were recorded. Results: Among the 316 screened patients with severe influenza pneumonia, 250 with acute respiratory failure requiring intubation met the criteria of ARDS, without having bacterial CAP. Among them, 72 patients developed NLRTI. The independent risk factors for NLRTI included immunosuppressant use before influenza infection [odds ratio (OR), 5.669; 95% confidence interval (CI), 1.770–18.154], extracorporeal membrane oxygenation (ECMO) use after ARDS (OR, 2.440; 95% CI, 1.214–4.904) and larger corticosteroid dosage after ARDS (OR, 1.209; 95% CI, 1.038–1.407). Patients with NLRTI had higher in-hospital mortality and longer ICU stay, hospitalization and duration on mechanical ventilation. Conclusion: We found that immunosuppressant use before influenza infection, ECMO use, and larger steroid dosage after ARDS independently predict NLRTI in influenza-related ARDS. Moreover, NLRTI results in poorer outcomes in patients with severe influenza. The reviews of this paper are available via the supplemental material section.

Abstract Background Patients with influenza complicated with pneumonia are at high risk of rapid progression to acute respiratory distress syndrome (ARDS). Prone positioning with longer duration and lung-protective strategies might reduce the mortality level in ARDS. The aim of this study is to investigate the survival predictors of prone positioning in patients with ARDS caused by influenza pneumonia. Methods This retrospective study was conducted by eight tertiary referral centers in Taiwan. From January 1 to March 31 in 2016, all of the patients in intensive care units with virology-proven influenza pneumonia were collected, while all of those patients with ARDS and receiving prone positioning were enrolled. Demographic data, laboratory examinations, management records, ventilator settings and clinical outcomes were collected for analysis. Results During the study period, 336 patients with severe influenza pneumonia were screened and 263 patients met the diagnosis of ARDS. Totally, 65 patients receiving prone positioning were included for analysis. The 60-day survivors had lower Acute Physiology and Chronic Health Evaluation (APACHE) II score, pneumonia severity index (PSI), creatinine level and lower rate of receiving renal replacement therapy than non-survivors (22.4 ± 8.5 vs. 29.2 ± 7.4, p = 0.003; 106.6 ± 40.9 vs. 135.3 ± 48.6, p = 0.019; 1.2 ± 0.9 mg/dL vs. 3.1 ± 3.6 mg/dL, p = 0.040; and 4% vs. 42%, p

Abstract Cyclic AMP receptor protein (CRP), a global regulator in Escherichia coli, regulates more than 180 genes via two roles: activation and repression. Few methods are available for predicting the regulatory roles from the binding sites of transcription factors. This work proposes an accurate method PredCRP to derive an optimised model (named PredCRP-model) and a set of four interpretable rules (named PredCRP-ruleset) for predicting and analysing the regulatory roles of CRP from sequences of CRP-binding sites. A dataset consisting of 169 CRP-binding sites with regulatory roles strongly supported by evidence was compiled. The PredCRP-model, using 12 informative features of CRP-binding sites, and cooperating with a support vector machine achieved a training and test accuracy of 0.98 and 0.93, respectively. PredCRP-ruleset has two activation rules and two repression rules derived using the 12 features and the decision tree method C4.5. This work further screened and identified 23 previously unobserved regulatory interactions in Escherichia coli. Using quantitative PCR for validation, PredCRP-model and PredCRP-ruleset achieved a test accuracy of 0.96 (=22/23) and 0.91 (=21/23), respectively. The proposed method is suitable for designing predictors for regulatory roles of all global regulators in Escherichia coli. PredCRP can be accessed at https://github.com/NctuICLab/PredCRP .

Abstract Background Afatinib is a second-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI). Compared to cytotoxic chemotherapy, afatinib has been shown to have better efficacy in the treatment of non-small cell lung cancer harboring EGFR mutations. However, 40 mg daily as the initial dose is often accompanied by serious adverse drug reactions (ADRs) and 28 to 53.3% of patients required a dose reduction. No previous study has compared the clinical efficacy and ADRs of different initial doses (40 mg vs. 30 mg daily) of afatinib in lung cancer treatment. Methods Patients with stage IV lung adenocarcinoma diagnosed and treated in two Kaohsiung Medical University-affiliated hospitals in Taiwan between May 2014 and August 2016 were identified and followed until December 2016. Demographic characteristics, responses, progression-free survival (PFS), overall survival (OS), and ADRs were recorded. Result A total of 48 patients with stage IV lung adenocarcinoma harboring susceptible EGFR mutations who received afatinib as their first-line therapy were enrolled. Patients using 30 mg daily as the initial dose tended to be older and female and have a smaller body size. The patients using 30 mg of afatinib daily as their initial dose had a similar response rate to those receiving 40 mg daily (76% vs. 95%, p = 0.0862) and the same disease control rate (100% vs. 100%, p = 0.1486). The PFS was similar between the patients receiving 30 mg or 40 mg of afatinib daily (median PFS: 469 vs. 443 days, log-rank p = 0.8418). Patients receiving 30 mg daily had a significantly lower incidence of diarrhea than those using 40 mg daily (41% vs. 100%, p

Abstract Background Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) such as gefitinib can provide better efficacy and prolonged progression free survival (PFS) than cytotoxic chemotherapy for metastatic lung non-squamous cell carcinoma harboring susceptible EGFR mutations when used as first-line therapy. Cytotoxic chemotherapy is regarded as being the standard therapy to overcome acquired resistance to an initial EGFR TKI. However, there is currently no consensus on how best to treat patients who develop resistance to both an initial EGFR TKI and chemotherapy. Methods We enrolled stage IV lung adenocarcinoma patients with an EGFR mutation and who had developed acquired resistance to gefitinib and cytotoxic chemotherapy from two university-affiliated hospitals in Taiwan from June 2011 to December 2014. Basic demographic data, included Eastern Cooperative Oncology Group (ECOG) performance status were collected, and the response rate, progression-free survival (PFS) and overall survival (OS) were analyzed. Result Two hundred and nine patients with mutated EGFR and who took gefitinib as the first-line therapy were identified in the study period, of whom 86 received second-line cytotoxic chemotherapy, and 60 who received third-line therapy were eligible for this study. The patients who received cytotoxic chemotherapy had a significantly higher disease control rate than those who received erlotinib (73% vs. 46%, p = 0.0363), however there were no significant differences in PFS (2.9 months vs. 3.1 months, p = 0.9049) and OS (8.9 months vs. 7.9 months, p = 0.4956). Platinum- or pemetrexed-based chemotherapy provided similar PFS and OS as others did. The only significant poor prognostic factors for OS were old age (≥65 years) (HR = 5.97 [2.65–13.44], p

Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive interstitial lung disease. Currently, therapeutic options are limited for this fatal disease. Curcumin, with its pleiotropic effects, has been studied for its potential therapeutic utilities in various diseases, including pulmonary fibrosis. However, the detailed mechanisms have not been studied comprehensively. We conducted a next-generation sequencing and bioinformatics study to investigate changes in the profiles of mRNA and microRNA after curcumin treatment in IPF fibroblasts. We identified 23 downregulated and 8 upregulated protein-coding genes in curcumin-treated IPF fibroblasts. Using STRING and IPA, we identified that suppression of cell cycle progression was the main cellular function associated with these differentially expressed genes. We also identified 13 downregulated and 57 upregulated microRNAs in curcumin-treated IPF fibroblasts. Further analysis identified a potential microRNA-mediated gene expression alteration in curcumin-treated IPF fibroblasts, namely, downregulated hsa-miR-6724-5p and upregulated KLF10. Therefore, curcumin might decrease the level of hsa-miR-6724-5p, leading to increased KLF10 expression, resulting in cell cycle arrest in curcumin-treated IPF fibroblasts. In conclusion, our findings might support the potential role of curcumin in the treatment of IPF, but further in-depth study is warranted to confirm our findings.

Fluid balance is a fundamental management of patients with sepsis, and this study aimed to investigate the impact of cumulative fluid balance on critically ill patients with influenza admitted to an intensive care unit (ICU).This multicenter retrospective cohort study was conducted by the Taiwan Severe Influenza Research Consortium (TSIRC) which includes eight medical centers. Patients with virology-proven influenza infection admitted to ICUs between October 2015 and March 2016 were included for analysis.A total of 296 patients were enrolled (mean age: 61.4±15.6 years; 62.8% men), and 92.2% (273/296) of them required mechanical ventilation. In the survivors, the daily fluid balance was positive from day 1 to day 3, and then gradually became negative from day 4 to day 7, whereas daily fluid balance was continuously positive in the non-survivors. Using the cumulative fluid balance from day 1-4 as a cut-off point, we found that a negative cumulative day 1-4 fluid balance was associated with a lower 30-day mortality rate (log-rank test, P = 0.003). To evaluate the impact of shock on this association, we divided the patients into shock and non-shock groups. The positive correlation between negative day 1-4 fluid balance and mortality was significant in the non-shock group (log-rank test, P = 0.008), but not in the shock group (log-rank test, P = 0.396). In a multivariate Cox proportional hazard regression model adjusted for age, sex, cerebrovascular disease, and PaO2/FiO2, day 1-4 fluid balance was independently associated with a higher 30-day mortality rate (aHR 1.088, 95% CI: 1.007-1.174).A negative day 1-4 cumulative fluid balance was associated with a lower mortality rate in critically ill patients with influenza. Our findings indicate the critical role of conservative fluid strategy in the management of patients with complicated influenza.

Although many studies show that the experience level of physicians is significantly associated with the outcomes of their patients, little evidence exists to show whether junior residents provide worse care than senior residents. This study was conducted to analyze whether the experience level of residents may affect the outcomes of patients cared for in a well-organized setting. We conducted a 7-year retrospective study utilizing statistical data from a respiratory care center (RCC) in a medical center between October 2004 and September 2011. In addition to the two medical residents who had been trained in the intensive care unit (ICU), the RCC team also included attending physicians in charge, a nurse practitioner, a case manager, a dietitian, a pharmacist, a social worker, registered respiratory therapists, and nursing staff. Weaning from mechanical ventilation was done according to an established weaning protocol. The 84 months analyzed were classified into five groups according to the levels of the two residents working in the RCC: R2 + R1, R2 + R2, R3 + R1, R3 + R2, and R3 + R3. The monthly weaning rate and mortality rate were the major outcomes, while the mean ventilator days, rate of return to the ICU, and nosocomial infection incidence rate were the minor outcomes. The groups did not differ significantly in the monthly weaning rate, mortality rate, mean ventilator days, rate of return to the ICU, or nosocomial infection incidence rate (p > 0.1). Further analysis showed no significant difference in the monthly weaning rate and mortality rate between months with a first-year resident (R1) and those with two senior residents (p > 0.2). Although the weaning rate in the RCC gradually improved over time (p 0.7). Thus, we concluded that in a well-organized setting, the levels (experiences) of residents did not significantly affect patient outcomes. This result may be attributed to the well-developed weaning protocol and teamwork processes in place, which avoid a large effect from any single factor and provide stable and high-quality care to the patients.

In this report, we describe a 31-year-old man in whom acute pancreatitis was the initial feature of a subsequently diagnosed pancreatic adenocarcinoma with multiple metastases. He initially presented at our hospital with acute pancreatitis. Abdominal ultrasonography revealed a mildly dilated pancreatic duct and an enlarged pancreatic head. Although a follow-up abdominal ultrasonography revealed a progressively dilated pancreatic duct and a progressively enlarged pancreatic head, he refused further investigation and was lost to follow-up. Four months later, he returned to our hospital with relapsed acute pancreatitis. Obstructive jaundice was noted and drainage was performed. Because choledochoplasty with multiple balloon catheters was not fully effective, biliary tract bypass surgery was carried out. Intraoperative biopsy confirmed pancreatic adenocarcinoma with multiple metastases. The patient died of massive gastrointestinal bleeding a few weeks later. To our knowledge, this is the youngest case of pancreatic cancer with the uncommon initial presentation of acute pancreatitis reported in the literature. For a patient with acute pancreatitis, particularly recurrent episodes, but with no known risk factors for pancreatitis, a pancreatic neoplasm should be considered as a potential underlying cause, even in a young man.

Self-contained underwater breathing apparatus (scuba) diving is increasingly popular in Taiwan. There are few references in the literature regarding pulmonary hemorrhage as the sole manifestation of pulmonary barotrauma in scuba divers, and no study from Taiwan was found in the literature. We present the case of a 25-year-old man who suffered alveolar hemorrhage related to pulmonary barotrauma as a complication of scuba diving. To our knowledge, this is the first case report describing a Taiwanese subject suffering from non-fatal pulmonary hemorrhage after scuba diving.

Increased incidence of erectile dysfunction (ED) has been reported among patients with sleep apnea (SA). However, this association has not been confirmed in a large-scale study. We therefore performed a population-based cohort study using Taiwan National Health Insurance (NHI) database to investigate the association of SA and ED. From the database of one million representative subjects randomly sampled from individuals enrolled in the NHI system in 2010, we identified adult patients having SA and excluded those having a diagnosis of ED prior to SA. From these suspected SA patients, those having SA diagnosis after polysomnography were defined as probable SA patients. The dates of their first SA diagnosis were defined as their index dates. Each SA patient was matched to 30 randomly-selected, age-matched control subjects without any SA diagnosis. The control subjects were assigned index dates as their corresponding SA patients, and were ensured having no ED diagnosis prior to their index dates. Totally, 4,835 male patients with suspected SA (including 1,946 probable SA patients) were matched to 145,050 control subjects (including 58,380 subjects matched to probable SA patients). The incidence rate of ED was significantly higher in probable SA patients as compared with the corresponding control subjects (5.7 vs. 2.3 per 1000 patient-year; adjusted incidence rate ratio = 2.0 [95% CI: 1.8-2.2], p

The structure of high-speed roller door with water film has improved in this study. The flameproof water film system is equipped with a water circulating device to reduce the water consumption of water film system. The water film is generated at the roller box of the high-speed roller door in this study. The heating test is done with the full-scale heating furnace. Both cases of the water film on unexposed surface and water film on exposed surface passed the fire resistance test based on ISO 834, proving that the high-speed roller door with water film system has 120A fire resistance period. The main findings indicate that the water film on exposed surface shows that as the amount of water film evaporated by high temperature inside the furnace must be greater than the evaporation capacity of water film on unexposed surface, the required water supply is 660 L more than the water film on unexposed surface.

Strongyloidiasis is endemic in tropic and subtropic areas, but is currently seldom encountered in developed area like Taiwan. We present an elder man with acute respiratory distress syndrome complicating Strongyloides stercoralis hyperinfection. There was no significant clue initially for diagnosing this patient as having S. stercoralis hyperinfection. Neither peripheral eosinophilia nor significant hemoptysis was noted. Bronchoscopy played a critical role to define the unexpected cause of his progressive pulmonary infiltrates. The correct diagnosis was soon made by recognition of the worm in bronchioloalveolar lavage cytology, and specific treatment was initiated promptly. For a septic patient with progressive pulmonary infiltrates, bronchoscopic studies including cytology may be necessary for defining the cause. Hyperinfection strongyloidiasis should be considered as a cause of acute respiratory distress syndrome in immunocompromised patient, especially with the presence of chronic gastrointestinal symptoms.

Asthma is a chronic inflammatory disorder of the airway, characterized by airway hyperresponsiveness. It is a disabling disease with an increasing prevalence, resulting in heavy social and economic burdens worldwide. Humans are extensively exposed to phthalates, and many epidemiological studies have shown a relationship between phthalate exposure and asthma in recent decades. Earlier experimental studies focused on inflammatory cells, demonstrating the adjuvant effects, immunomodulatory effects, or immunosuppressive effects related to phthalate exposure. Recent studies have shown that phthalates may have a direct effect on airway epithelial cells and contribute to airway remodeling, which is the cardinal pathologic characteristic of chronic asthma, with a high correlation with disease severity. Through these efforts, phthalates have been recognized as important environmental factors in the pathogenesis of asthma, but further studies are still required to elucidate the detailed mechanism. This review discusses the current status of human exposure to phthalates in Taiwan and summarizes the epidemiological and experimental evidence related to the roles of phthalate exposure in the development of asthma and associated diseases.

Background: To date, studies investigating the association between pre-biologic biomarker levels and post-biologic outcomes have been limited to single biomarkers and assessment of biologic efficacy from structured clinical trials. Aim: To elucidate the associations of pre-biologic individual biomarker levels or their combinations with pre-to-post biologic changes in asthma outcomes in real-life. Methods: This was a registry-based, cohort study using data from 23 countries, which shared data with the International Severe Asthma Registry (May 2017-February 2023). The investigated biomarkers (highest pre-biologic levels) were immunoglobulin E (IgE), blood eosinophil count (BEC) and fractional exhaled nitric oxide (FeNO). Pre- to approximately 12-month post-biologic change for each of three asthma outcome domains (i.e. exacerbation rate, symptom control and lung function), and the association of this change with pre-biologic biomarkers was investigated for individual and combined biomarkers. Results: Overall, 3751 patients initiated biologics and were included in the analysis. No association was found between pre-biologic BEC and pre-to-post biologic change in exacerbation rate for any biologic class. However, higher prebiologic BEC and FeNO were both associated with greater post-biologic improvement in FEV1 for both anti-IgE and anti-IL5/5R, with a trend for anti-IL4Rα. Mean FEV1 improved by 27-178 mL post-anti-IgE as pre-biologic BEC increased (250 to 1000 cells/µL), and by 43-216 mL and 129-250 mL post-anti-IL5/5R and -anti-IL4Rα, respectively along the same BEC gradient. Corresponding improvements along a FeNO gradient (25-100 ppb) were 41-274 mL, 69-207 mL and 148-224 mL for anti-IgE, anti-IL5/5R, and anti-IL4Rα, respectively. Higher baseline BEC was also associated with lower probability of uncontrolled asthma (OR 0.39; p=0.001) post-biologic for anti-IL5/5R. Prebiologic IgE was a poor predictor of subsequent pre-to-post-biologic change for all outcomes assessed for all biologics. The combination of BEC + FeNO marginally improved the prediction of post-biologic FEV1 increase (adjusted R²: 0.751), compared to BEC (adjusted R²: 0.747) or FeNO alone (adjusted R²: 0.743) (p=0.005 and <0.001, respectively); however, this prediction was not improved by the addition of IgE. Conclusions: The ability of higher baseline BEC, FeNO and their combination to predict biologic-associated lung function improvement may encourage earlier intervention in patients with impaired lung function or at risk of accelerated lung function decline. [ABSTRACT FROM AUTHOR]