Genome-wide association study identifies novel susceptible loci and evaluation of polygenic risk score for chronic obstructive pulmonary disease in a Taiwanese population.

BACKGROUND: Chronic Obstructive Pulmonary Disease (COPD) describes a group of progressive lung diseases causing breathing difficulties. While COPD development typically involves a complex interplay between genetic and environmental factors, genetics play a role in disease susceptibility. This study used genome-wide association studies (GWAS) and polygenic risk score (PRS) to elucidate the genetic basis for COPD in Taiwanese patients. RESULTS: GWAS was performed on a Taiwanese COPD case-control cohort with a sample size of 5,442 cases and 17,681 controls. Additionally, the PRS was calculated and assessed in our target groups. GWAS results indicate that although there were no single nucleotide polymorphisms (SNPs) of genome-wide significance, prominent COPD susceptibility loci on or nearby genes such as WWTR1, EXT1, INTU, MAP3K7CL, MAMDC2, BZW1/CLK1, LINC01197, LINC01894, and CFAP95 (C9orf135) were identified, which had not been reported in previous studies. Thirteen susceptibility loci, such as CHRNA4, AFAP1, and DTWD1, previously reported in other populations were replicated and confirmed to be associated with COPD in Taiwanese populations. The PRS was determined in the target groups using the summary statistics from our base group, yielding an effective association with COPD (odds ratio [OR] 1.09, 95% confidence interval [CI] 1.02-1.17, p = 0.011). Furthermore, replication a previous lung function trait PRS model in our target group, showed a significant association of COPD susceptibility with PRS of Forced Expiratory Volume in one second (FEV1)/Forced Vital Capacity (FCV) (OR 0.89, 95% CI 0.83-0.95, p = 0.001). CONCLUSIONS: Novel COPD-related genes were identified in the studied Taiwanese population. The PRS model, based on COPD or lung function traits, enables disease risk estimation and enhances prediction before suffering. These results offer new perspectives on the genetics of COPD and serve as a basis for future research.

Ultralow-Energy-Consumption Photosynaptic Transistor Utilizing Conjugated Polymers/Perovskite Quantum Dots Nanocomposites With Ligand Density Optimization.

The photosynaptic transistor stands as a promising contender for overcoming the von Neumann bottleneck in the realm of photo-communication. In this context, photonic synaptic transistors is developed through a straightforward solution process, employing an organic semiconducting polymer with pendant-naphthalene-containing side chains (PDPPNA) in combination with ligand-density-engineered CsPbBr3 perovskite quantum dots (PQDs). This fabrication approach allows the devices to emulate fundamental synaptic behaviors, encompassing excitatory postsynaptic current, paired-pulse facilitation, the transition from short-to-long-term memory, and the concept of "learning experience." Notably, the phototransistor, incorporating the blend of the PDPPNA and CsPbBr3 PQDs washed with ethyl acetate, achieved an exceptional memory ratio of 104. Simultaneously, the same device exhibited an impressive paired-pulse facilitation ratio of 223% at a moderate operating voltage of -4 V and an extraordinarily low energy consumption of 0.215 aJ at an ultralow operating voltage of -0.1 mV. Consequently, these low-voltage synaptic devices, constructed with a pendant side-chain engineering of organic semiconductors and a ligand density engineering of PQDs through a simple fabrication process, exhibit substantial potential for replicating the visual memory capabilities of the human brain.

Rate of graft retear is higher in over-the-top superior capsular reconstruction for massive posterosuperior rotator cuff tears with subscapularis tear.

PURPOSE: To compare side-to-side superior capsular reconstruction (SCR) with over-the-top SCR in terms of functional outcomes, pain relief and allograft survival rates. METHODS: Patients who had undergone arthroscopic dermal allograft SCR for massive irreparable rotator cuff tears and clinical follow-up for ≥2 years were recruited. All patients underwent postoperative assessment with routine radiographic analysis for acromiohumeral distances, ultrasound imaging 1 and 3 months after SCR and magnetic resonance imaging (MRI) at least 12 months after SCR. The outcome measures were visual analogue scale (VAS), American Shoulder and Elbow Surgeons (ASES), Constant and Single Assessment Numeric Evaluation (SANE) scores. RESULTS: SCR was performed in 56 patients including side-to-side SCR in 32 and over-the-top SCR in 24. Postoperative MRI showed that the grafts were intact in 46 patients (82.1%; 26 who underwent side-to-side SCR and 20 who underwent over-the-top SCR). The proportion of nonhealing grafts in the over-the-top group was significantly higher with concomitant subscapularis tears (60% vs. 5.3%; p = 0.02). VAS scores and functional outcomes improved postoperatively in both groups and postoperative VAS (1.4 vs. 1.7; n.s.), Constant (74.8 vs. 76.0; n.s.), mean ASES (87.4 vs. 89.1; n.s.) and mean SANE (81.7 vs. 84.3; n.s.) scores did not differ significantly. CONCLUSION: For massive rotator cuff tears, over-the-top and side-to-side SCR achieve similar pain relief and functional improvement, and the rate of healing allografts is high. However, over-the-top SCR is not recommended for massive posterosuperior rotator cuff tears with repairable subscapularis tendon tears due to a higher nonhealing rate. LEVEL OF EVIDENCE: Level III.

Design and Implementation of an Intensive Care Unit Command Center for Medical Data Fusion.

The rapid advancements in Artificial Intelligence of Things (AIoT) are pivotal for the healthcare sector, especially as the world approaches an aging society which will be reached by 2050. This paper presents an innovative AIoT-enabled data fusion system implemented at the CMUH Respiratory Intensive Care Unit (RICU) to address the high incidence of medical errors in ICUs, which are among the top three causes of mortality in healthcare facilities. ICU patients are particularly vulnerable to medical errors due to the complexity of their conditions and the critical nature of their care. We introduce a four-layer AIoT architecture designed to manage and deliver both real-time and non-real-time medical data within the CMUH-RICU. Our system demonstrates the capability to handle 22 TB of medical data annually with an average delay of 1.72 ms and a bandwidth of 65.66 Mbps. Additionally, we ensure the uninterrupted operation of the CMUH-RICU with a three-node streaming cluster (called Kafka), provided a failed node is repaired within 9 h, assuming a one-year node lifespan. A case study is presented where the AI application of acute respiratory distress syndrome (ARDS), leveraging our AIoT data fusion approach, significantly improved the medical diagnosis rate from 52.2% to 93.3% and reduced mortality from 56.5% to 39.5%. The results underscore the potential of AIoT in enhancing patient outcomes and operational efficiency in the ICU setting.

Ring-Embedded Finger Over Proximal Interphalangeal Joint with Preserved Neurovascularization: A Case Report and Literature Review.

CASE: We present a unique case of a 45-year-old man with his right middle finger embedded with rings. Limited finger flexion was noted because of flexor tendon injury caused by the dorsal migration of the embedded ring through joint. The rings were removed under anesthesia, resulting in the resolution of swelling and recover of osseous structure. Follow-up examinations revealed no residual edema or numbness, indicating preserved neurovascularization, despite the dorsal migration of the ring. CONCLUSION: Our unique case reveals continuous finger ring migration without compromising neurovascular bundles, with review of 30 cases emphasizing the importance of psychiatric consultation. Timely intervention yielded nearly half of patients achieving full recovery.

Impact of unplanned second debridement, antibiotics and implant retention on long-term outcomes in knee exchange arthroplasty: Elevated risk of failure and reinfection.

Purpose: This study investigates the outcomes of two-stage exchange arthroplasty (EA) for periprosthetic joint infection (PJI) following initial or unplanned repeat debridement antibiotics, and implant retention (DAIR). Methods: We retrospectively reviewed cases of knee arthroplasty infection treated with two-stage EA after DAIR, spanning from January 1994 to December 2010. A total of 138 patients were included, comprising 112 with initial DAIR and 26 with an unplanned second DAIR. Data on demographics, comorbidities, infection characteristics and causative organisms were analyzed. The primary outcome was implant failure or reinfection, observed over a minimum follow-up of 10 years. Results: The overall success rate for two-stage EA was 87% (119/138 patients). Factors identified for treatment failure included reinfection with the same pathogen for unplanned second DAIR (hazard ratio [HR] = 3.41; 95% confidence interval [CI] = 1.35-4.38; p = 0.004), higher reinfection rates in patients undergoing EA after an unplanned second DAIR, especially with a prior history of PJI within 2 years (HR = 4.23; 95% CI = 2.39-5.31; p = 0.002), pre-first DAIR C-reactive protein (CRP) levels over 100 mg/dL (HR = 2.52; 95% CI = 1.98-3.42; p = 0.003) and recurrence with the same pathogen (HR = 2.35; 95% CI = 1.32-4.24; p = 0.007). Additional factors such as male gender (HR = 3.92; 95% CI = 1.21-5.25; p = 0.007) and osteoporosis (T score < -2.5; HR = 3.27; 95% CI = 1.23-5.28; p = 0.005) were identified as risk factors for implant failure in all EA cases. Conclusions: This study identifies key risk factors for worse knee EA outcomes following DAIR, including a pre-first DAIR CRP level over 100 mg/L, same pathogen recurrence, and PJI history within 2 years. It shows implant failure rates remain constant across EA cases, regardless of DAIR sequence, particularly with risk factors like male gender and severe osteoporosis (T score < -2.5). These results underscore the need for careful evaluation before an unplanned second DAIR, given its significant impact on EA success. Level of Evidence: Level III.

Reduced mortality with antimicrobial stewardship guided by BioFire FilmArray Blood Culture Identification 2 panel in critically ill patients with bloodstream infection: a retrospective propensity score-matched study.

OBJECTIVES: To investigate whether using the BioFire® FilmArray® Blood Culture Identification 2 panel (BCID2) leads to timely antimicrobial therapy and improves patient outcomes in critically ill patients with bloodstream infections (BSIs). METHODS: This retrospective observational study included patients with BSIs admitted to the intensive care unit from July 1, 2021, to August 31, 2023. Patients were divided into groups receiving appropriate or inappropriate antimicrobial therapy. Those receiving inappropriate therapy underwent adjustments using standard-of-care (SOC) testing or BCID2. Propensity score matching (PSM) was performed on the original cohort (Model 1) and a time-window bias-adjusted cohort (Model 2). Clinical impact of BCID2-guided antimicrobial adjustment was analyzed in both models. RESULTS: A total of 181 patients received inappropriate antimicrobial therapy, with 33 undergoing BCID2 testing and 148 undergoing SOC testing. Following PSM and time-window bias adjustment, 66 patients were analyzed in Model 1 and 46 patients in Model 2. BCID2 significantly reduced the median time to appropriate antimicrobial therapy (40.8 vs. 74.0 h in Model 1; 42.8 vs. 68.9 h in Model 2) and the day-28 mortality rate (27.8% vs. 77.1%, p < 0.001 in Model 1; 23.5% vs. 58.6%, p = 0.021 in Model 2). In multivariate regression analysis, BCID2-guided antimicrobial adjustment was an independent prognostic factor for day-28 mortality (adjusted odds ratio [aOR] 0.07 in Model 1 and aOR 0.12 in Model 2). CONCLUSION: BCID2-guided antimicrobial stewardship was associated with a shorter time to appropriate antimicrobial therapy and reduced day-28 mortality in critically ill patients with BSIs receiving inappropriate antimicrobial therapy.

Reversible Molecular Conformation Transitions of Smectic Liquid Crystals for Light/Bias-Gated Transistor Memory.

In recent years, organic photonic field-effect transistors have made remarkable progress with the rapid development of conjugated polycrystalline materials. Liquid crystals, with their smooth surface, defined layer thickness, and crystalline structures, are commonly used for these advantages. In this work, a series of smectic liquid crystalline molecules, 2,9-didecyl-dinaphtho-thienothiophene (C10-DNTT), 2,7-didecyl-benzothieno-benzothiopene (C10-BTBT), 3,9-didecyl-dinaphtho-thiophene (C10-DNT), and didecyl-sexithiophene (C10-6T), have been used in photonic transistor memory, functioning as both hole-transport channels and electron traps to investigate systematically the reasons and mechanisms behind the memory behavior of smectic liquid crystals. After thermal annealing, C10-BTBT and C10-6T/C10-DNTT are homeotropically aligned from the smectic A and smectic X phases, respectively. The 3D-ordered structure of these smectic-aligned crystals contributed to efficient photowriting and electrical erasing processes. Among them, the device performance of C10-BTBT was particularly significant, with a memory window of 21 V. The memory ratio could reach 1.5 × 106 and maintain a memory ratio of over 3 orders after 10,000 s, contributing to its smectic A structure. Through the research, we confirmed the memory and light/bias-gated behaviors of these smectic liquid crystalline molecules, attributing them to reversible molecular conformation transitions and the inherent structural inhomogeneity inside the polycrystalline channel layer.

High mortality of patients with severe pneumonia caused by respiratory syncytial virus, August 2021-June 2023, Taiwan.

Among the 14 patients with respiratory syncytial virus pneumonia, the majority (n = 8, 57.1 %) were older than 65 years and had health care-associated pneumonia (57.1 %). Over 70 % (n = 10) of them exhibited bacterial co-infection, with a high proportion (64.3 %) requiring mechanical ventilation. The hospital mortality rate was 50 %.

Application of a multiplex molecular pneumonia panel and real-world impact on antimicrobial stewardship among patients with hospital-acquired and ventilator-associated pneumonia in intensive care units.

BACKGROUND: The optimal timing for applying the BioFire FilmArray Pneumonia Panel (FAPP) in intensive care unit (ICU) patients with hospital-acquired pneumonia (HAP) or ventilator-associated pneumonia (VAP) remains undefined, and there are limited data on its impact on antimicrobial stewardship. METHODS: This retrospective study was conducted at a referral hospital in Taiwan from November 2019 to October 2022. Adult ICU patients with HAP/VAP who underwent FAPP testing were enrolled. Patient data, FAPP results, conventional microbiological testing results, and the real-world impact of FAPP results on antimicrobial therapy adjustments were assessed. Logistic regression was used to determine the predictive factors for bacterial detection by FAPP. RESULTS: Among 592 respiratory specimens, including 564 (95.3%) endotracheal aspirate specimens, 19 (3.2%) expectorated sputum specimens and 9 (1.5%) bronchoalveolar lavage specimens, from 467 patients with HAP/VAP, FAPP testing yielded 368 (62.2%) positive results. Independent predictors for positive bacterial detection by FAPP included prolonged hospital stay (odds ratio [OR], 3.14), recent admissions (OR, 1.59), elevated C-reactive protein levels (OR, 1.85), Acute Physiology and Chronic Health Evaluation II scores (OR, 1.58), and septic shock (OR, 1.79). Approximately 50% of antimicrobial therapy for infections caused by Gram-negative bacteria and 58.4% for Gram-positive bacteria were adjusted or confirmed after obtaining FAPP results. CONCLUSIONS: This study identified several factors predicting bacterial detection by FAPP in critically ill patients with HAP/VAP. More than 50% real-world clinical practices were adjusted or confirmed based on the FAPP results. Clinical algorithms for the use of FAPP and antimicrobial stewardship guidelines may further enhance its benefits.

The real-world impact of the BioFire FilmArray blood culture identification 2 panel on antimicrobial stewardship among patients with bloodstream infections in intensive care units with a high burden of drug-resistant pathogens.

BACKGROUND: The increasing prevalence of drug-resistant pathogens leads to delays in adequate antimicrobial treatment in intensive care units (ICU). The real-world influence of the BioFire FilmArray Blood Culture Identification 2 (BCID2) panel on pathogen identification, diagnostic concordance with conventional culture methods, and antimicrobial stewardship in the ICU remains unexplored. METHODS: This retrospective observational study, conducted from July 2021 to August 2023, involved adult ICU patients with positive blood cultures who underwent BCID2 testing. The concordance between BCID2 and conventional culture results was examined, and its impact on antimicrobial stewardship was assessed through a comprehensive retrospective review of patient records by intensivists. RESULTS: A total of 129 blood specimens from 113 patients were analysed. Among these patients, a high proportion of drug-resistant strains were noted, including carbapenem-resistant Klebsiella pneumoniae (CRKP) (57.1%), carbapenem-resistant Acinetobacter calcoaceticus-baumannii complex (100%), methicillin-resistant Staphylococcus aureus (MRSA) (70%), and vancomycin-resistant Enterococcus faecium (VRE) (100%). The time from blood culture collection to obtaining BCID2 results was significantly shorter than conventional culture (46.2 h vs. 86.9 h, p < 0.001). BCID2 demonstrated 100% concordance in genotype-phenotype correlation in antimicrobial resistance (AMR) for CRKP, carbapenem-resistant Escherichia coli, MRSA, and VRE. A total of 40.5% of patients received inadequate empirical antimicrobial treatment. The antimicrobial regimen was adjusted or confirmed in 55.4% of patients following the BCID2 results. CONCLUSIONS: In the context of a high burden of drug-resistant pathogens, BCID2 demonstrated rapid pathogen and AMR detection, with a noticeable impact on antimicrobial stewardship in BSI in the ICU.

Comparison of continuous 24-hour and 14-day ECG monitoring for the detection of cardiac arrhythmias in patients with ischemic stroke or syncope.

BACKGROUND: Previous studies show that using 12-lead electrocardiogram (ECG) or 24-h ECG monitor for the detection of cardiac arrhythmia events in patients with stroke or syncope is ineffective. HYPOTHESIS: The 14-day continuous ECG patch has higher detection rates of arrhythmias compared with conventional 24-h ECG monitoring in patients with ischemic stroke or syncope. METHODS: This cross-sectional study of patients with newly diagnosed ischemic stroke or syncope received a 24-h ECG monitoring and 14-day continuous cardiac monitoring patch and the arrhythmia events were measured. RESULTS: This study enrolled 83 patients with ischemic stroke or syncope. The detection rate of composite cardiac arrhythmias was significantly higher for the 14-day ECG patch than 24-h Holter monitor (69.9% vs. 21.7%, p = .006). In patients with ischemic stroke, the detection rates of cardiac arrhythmias were 63.4% for supraventricular tachycardia (SVT), 7% for ventricular tachycardia (VT), 5.6% for atrial fibrillation (AF), 4.2% for atrioventricular block (AVB), and 1.4% for pause by 14-day ECG patch, respectively. The significant difference in arrhythmic detection rates were found for SVT (45.8%), AF (6%), pause (1.2%), AVB (2.4%), and VT (9.6%) by 14-day ECG patch but not by 24-h Holter monitor in patients with ischemic stroke or syncope. CONCLUSIONS: A 14-day ECG patch can be used on patients with ischemic stroke or syncope for the early detection of AF or other cardiac arrhythmia events. The patch can be helpful for physicians in planning medical or mechanical interventions of patients with ischemic stroke and occult AF.

Clinical characteristics and treatment outcomes among the hospitalized elderly patients with COVID-19 during the late pandemic phase in central Taiwan.

BACKGROUND: There is a lack of information regarding outcomes of elderly patients hospitalized with COVID-19 following the widespread use of COVID-19 vaccines and antiviral agents. METHODS: A retrospective study was conducted between January and August 2022, enrolling patients aged 65 years or older. Patients were categorized into two groups: 'old' (65-79 years) and 'oldest-old' (80 years or more). Multivariate regression was employed to identify independent prognostic factors for in-hospital mortality. RESULTS: A total of 797 patients were enrolled, including 428 old and 369 oldest-old patients. In each subgroup, 66.6 % and 59.6 % of patients received at least one dose of the COVID-19 vaccine, respectively. Approximately 40 % of the patients received oral antiviral agents either before or upon hospital admission. A greater percentage of the oldest-old patients received remdesivir (53.4 % versus 39.7 %, p < 0.001), dexamethasone (49.3 % versus 36.7 %, p < 0.001), and tocilizumab (10.0 % versus 6.8 %, p < 0.001) than old patients. The mortality rate was comparable between the two age subgroups (14 % versus 15.2 %). Independent predictors of in-hospital mortality included disease severity and comorbidities such as end-stage renal disease (ESRD), cirrhosis, solid tumours, and haematologic malignancies. Ageing was not correlated with increased in-hospital mortality across all comorbidity subgroups. CONCLUSIONS: In the later stages of the pandemic, with widespread vaccination and advancements in COVID-19 treatments, outcomes for hospitalized elderly and oldest-old patients with COVID-19 have improved. The influence of age on in-hospital mortality has diminished, while comorbidities such as ESRD, cirrhosis, solid tumours, and hematologic malignancies have been associated with mortality.

Assessing mortality risk in Type 2 Diabetes patients with prolonged ASCVD risk factors: the inclusive Poh-Ai predictive scoring system with CAC Score integration.

PURPOSE: To enhance the predictive risk model for all-cause mortality in individuals with Type 2 Diabetes (T2DM) and prolonged Atherosclerotic Cardiovascular Disease (ASCVD) risk factors. Despite the utility of the Coronary Artery Calcium (CAC) score in assessing cardiovascular risk, its capacity to predict all-cause mortality remains limited. METHODS: A retrospective cohort study included 1929 asymptomatic T2DM patients with ASCVD risk factors, aged 40-80. Variables encompassed demographic attributes, clinical parameters, CAC scores, comorbidities, and medication usage. Factors predicting all-cause mortality were selected to create a predictive scoring system. By using stepwise selection in a multivariate Cox proportional hazards model, we divided the patients into three risk groups. RESULTS: In our analysis of all-cause mortality in T2DM patients with extended ASCVD risk factors over 5 years, we identified significant risk factors, their adjusted hazard ratios (aHR), and scores: e.g., CAC score > 1000 (aHR: 1.57, score: 2), CAC score 401-1000 (aHR: 2.05, score: 2), and more. These factors strongly predict all-cause mortality, with varying risk groups (e.g., very low-risk: 2.0%, very high-risk: 24.0%). Significant differences in 5-year overall survival rates were observed among these groups (log-rank test < 0.001). CONCLUSION: The Poh-Ai Predictive Scoring System excels in forecasting mortality and cardiovascular events in individuals with Type 2 Diabetes Mellitus and extended ASCVD risk factors.

High-Thermal Stable Epoxy Resin through Blending Nanoarchitectonics with Double-Decker-Shaped Polyhedral Silsesquioxane-Functionalized Benzoxazine Derivatives.

A series of di-functional benzoxazine (BZ) monomers was synthesized, specifically the double-decker silsesquioxane (DDSQ) cage structure (DDSQ-BZ). Comparative analyses were conducted between DDSQ-BZ monomers and the most commonly utilized bisphenol A-functionalized bifunctional benzoxazine (BPA-BZ) monomer. DDSQ-BZ compounds possess better thermal properties such as high char yield and high thermal decomposition temperature (Td10) after thermal ring-opening polymerization (ROP) because the inorganic DDSQ cage nanostructure features a nano-reinforcement effect. In addition, blending inorganic DDSQ-BZ compounds with epoxy resin was explored to form organic/inorganic hybrids with enhanced thermal and mechanical properties following thermal ROP. The improvement in mechanical properties is primarily attributed to the network structure formed by the cross-linking between DDSQ-BZ and the epoxy resin during thermal ROP, as well as hydrogen bonding interactions formed between the hydroxyl groups generated during thermal ROP and the Si-O-Si bonds in the DDSQ structure.