Sepsis Alert Systems, Mortality, and Adherence in Emergency Departments: A Systematic Review and Meta-Analysis.

Importance: Early detection and management of sepsis are crucial for patient survival. Emergency departments (EDs) play a key role in sepsis management but face challenges in timely response due to high patient volumes. Sepsis alert systems are proposed to expedite diagnosis and treatment initiation per the Surviving Sepsis Campaign guidelines. Objective: To review and analyze the association of sepsis alert systems in EDs with patient outcomes. Data Sources: A thorough search was conducted in PubMed, EMBASE, Web of Science, and the Cochrane Library from January 1, 2004, to November 19, 2023. Study Selection: Studies that evaluated sepsis alert systems specifically designed for adult ED patients were evaluated. Inclusion criteria focused on peer-reviewed, full-text articles in English that reported on mortality, ICU admissions, hospital stay duration, and sepsis management adherence. Exclusion criteria included studies that lacked a control group or quantitative reports. Data Extraction and Synthesis: The review followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline. Two independent reviewers conducted the data extraction using a standardized form. Any disagreements were resolved through discussion. The data were synthesized using a random-effects model due to the expected heterogeneity among the included studies. Main Outcomes and Measures: Key outcomes included mortality, intensive care unit admissions, hospital stay duration, and adherence to the sepsis bundle. Results: Of 3281 initially identified studies, 22 (0.67%) met inclusion criteria, encompassing 19 580 patients. Sepsis alert systems were associated with reduced mortality risk (risk ratio [RR], 0.81; 95% CI, 0.71 to 0.91) and length of hospital stay (standardized mean difference [SMD], -0.15; 95% CI, -0.20 to -0.11). These systems were also associated with better adherence to sepsis bundle elements, notably in terms of shorter time to fluid administration (SMD, -0.42; 95% CI, -0.52 to -0.32), blood culture (SMD, -0.31; 95% CI, -0.40 to -0.21), antibiotic administration (SMD, -0.34; 95% CI, -0.39 to -0.29), and lactate measurement (SMD, -0.15; 95% CI, -0.22 to -0.08). Electronic alerts were particularly associated with reduced mortality (RR, 0.78; 95% CI, 0.67 to 0.92) and adherence with blood culture guidelines (RR, 1.14; 95% CI, 1.03 to 1.27). Conclusions and Relevance: These findings suggest that sepsis alert systems in EDs were associated with better patient outcomes along with better adherence to sepsis management protocols. These systems hold promise for enhancing ED responses to sepsis, potentially leading to better patient outcomes.

Implications of TP-positive CAFs in the Bone Invasion of Oral Squamous Cell Carcinoma.

BACKGROUND/AIM: Cancer-associated fibroblasts (CAFs) have recently been suggested as critical cellular components of bone invasion in oral squamous cell carcinoma (OSCC). However, the underlying molecular mechanisms and subtypes related to their bone-invasive function are unclear. This study investigated the implications of thymidine phosphorylase (TP)-positive CAFs (TP+CAFs) in OSCC bone invasion. MATERIALS AND METHODS: TP expression was determined in 116 patients with OSCC using immunohistochemistry. The influence of TP expression on the biological behavior of CAFs was investigated in vitro. The possible impact of TP+CAFs on bone invasion in OSCC was further evaluated using patient-derived xenograft (PDX) mouse models. RESULTS: In bone-invasive OSCC tissues, TP+CAFs were mainly distributed on the surface of resorbed bone tissue rather than on the tumor side. High levels of TP+CAFs were significantly associated with higher T-stage, bone invasion, and worse overall survival and recurrence-free survival in our study cohort. Recombinant human TP promoted the proliferative and invasive abilities of CAFs and increased matrix metalloproteinase-9 mRNA expression in vitro, related to bone resorption. In the PDX mouse models, TP+CAFs were found in early bone resorption on the surface of resorbed bony tissues. Bone resorption occurred more frequently in the PDX models with TP+CAFs than in those without. CONCLUSION: TP+CAFs were significantly associated with bone invasion and the prognosis of OSCC. This study provides insights into cellular and molecular targets for the early diagnosis and treatment of bone-invasive OSCC.

Is immediate dental implant in fibula free flap beneficial for implant survival and osteoradionecrosis in jaw reconstruction?

OBJECTIVES: This study aimed to compare the risk of osteoradionecrosis and implant survival in oral cancer patients undergoing immediate dental implants during jaw reconstruction, termed "Jaw in a Day" (JIAD), with those receiving no implants or delayed implants (non-JIAD). PATIENTS & METHODS: Clinicopathologic data were collected from prospectively enrolled JIAD patients (n = 10, 29 implants) and retrospectively from non-JIAD patients (n = 117, 86 implants). Survival analyses were performed to assess implant survival and osteoradionecrosis-free survival. RESULTS: Osteoradionecrosis occurred in 0 % of JIAD cases compared to 19.3 % in non-JIAD cases without implants and 71.4 % in non-JIAD cases with delayed implants (p = 0.008). Osteoradionecrosis-free survival was significantly better in the JIAD group than the non-JIAD group (p = 0.0059). Implants in the JIAD group all survived regardless of radiation therapy (29/29, 100 %) and 95.1 % (58/61) of implants survived in delayed implants in non-irradiated fibula without radiotherapy. Meanwhile, only 11 of 25 implants placed in irradiated fibula flaps survived, even when the implants were placed after a median time interval of 624 days after radiotherapy, and none of them were earlier than 360 days. The survival analysis revealed a significant difference (p < 0.0001). CONCLUSION: JIAD appears to offer superior outcomes in terms of implant survival and osteoradionecrosis prevention compared to delayed implant placement. Placing implants in irradiated fibula, even after years, significantly poses high risk of implant failure and osteoradionecrosis. JIAD represents a promising approach for optimal rehabilitation, particularly in oral cancer patients requiring postoperative radiotherapy. Proper positioning and orientation of implants and flaps are crucial for implant survival.

Occupational and environmental risk factors for idiopathic pulmonary fibrosis: A case-control study.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung disease of unknown etiology. The aim of this study was to evaluate the environmental and occupational risk factors of IPF. METHODS: This hospital-based, case-control study included 206 patients with IPF selected from the Seoul National University Bundang Hospital Interstitial Lung Disease registry and 167 controls without lung disease. Data on occupation, lifestyle, transportation, and types of environmental and occupational dust exposure were obtained using a questionnaire. IPF diagnosis was confirmed based on the recent guidelines, and the possibility of hypersensitivity pneumonitis was excluded. Multiple logistic regression was performed to determine the risk factors for IPF. RESULTS: After adjusting for age and sex, ever-smokers (odds ratio [OR], 2.35; 95 % confidence interval [CI]: 1.51-3.68) and individuals who smoked more than 30 pack-years (OR, 2.79; 95%CI: 1.70-4.68) showed an increased risk for IPF. Any occupational dust exposure (adjusted OR, 2.08; 95%CI: 1.19-3.72), especially exposure to chemicals (adjusted OR, 3.52; 99%CI: 1.56-9.05), was associated with IPF after adjusting for age, sex, and smoking. CONCLUSIONS: Smoking and occupational dust exposure are associated with an increased risk for IPF. Both factors have dose and duration-dependent relationships with the risk for IPF.

Consecutive assessment of recovery after peripheral nerve injury of the sciatic nerve within the same rat using PET/MRI.

BACKGROUND: Positron emission tomography (PET) has been reported as effective in diagnosing peripheral nerve injury (PNI). However, there is a lack of studies evaluating different degrees of PNI using PET within the same individual to reduce errors due to interindividual differences. PURPOSE: To evaluate the recovery process in the same rat after sciatic nerve injury using PET/magnetic resonance imaging (MRI). MATERIAL AND METHODS: Crushing nerve injuries were induced in the left sciatic nerves of six male rats, preserving the right ones. The degree of nerve damage was measured at one, two, three, four, and five weeks postoperatively using three assessment methods: paw withdrawal threshold test (RevWT); PET (SUVR); and MRI (MRSIR). All the representing values of each method are presented as ratio values of the right and left sides in each rat. RESULTS: Significant gradual recovery of all rats was observed over time in all the methods. No significant differences in RevWT and MRSIR were observed between before and more than four weeks after injury, whereas a significant difference in SUVR was still observed between before and five weeks after injury (P = 0.0007). The parameters of all methods decreased significantly over time (P = 0.000, all), and the explanatory power was significant in RevWT, SUVR, and MRSIR. CONCLUSION: PET and MRI could be valuable non-invasive techniques for diagnosing neuropathic pain resulting from PNI. PET/MRI would be expected to be a more accurate and informative diagnostic tool for PNI than MRI alone.

Clinical Efficacy and Safety of an Automatic Closed-Suction System in Mechanically Ventilated Patients with Pneumonia: A Multicenter, Prospective, Randomized, Non-Inferiority, Investigator-Initiated Trial.

Endotracheal suctioning is an essential but labor-intensive procedure, with the risk of serious complications. A brand new automatic closed-suction device was developed to alleviate the workload of healthcare providers and minimize those complications. We evaluated the clinical efficacy and safety of the automatic suction system in mechanically ventilated patients with pneumonia. In this multicenter, randomized, non-inferiority, investigator-initiated trial, mechanically ventilated patients with pneumonia were randomized to the automatic device (intervention) or conventional manual suctioning (control). The primary efficacy outcome was the change in the modified clinical pulmonary infection score (CPIS) in 3 days. Secondary outcomes were the frequency of additional suctioning and the amount of secretion. Safety outcomes included adverse events or complications. A total of 54 participants, less than the pre-determined number of 102, were enrolled. There was no significant difference in the change in the CPIS over 72 h (-0.13 ± 1.58 in the intervention group, -0.58 ± 1.18 in the control group, p = 0.866), but the non-inferiority margin was not satisfied. There were no significant differences in the secondary outcomes and safety outcomes, with a tendency for more patients with improved tracheal mucosal injury in the intervention group. The novel automatic closed-suction system showed comparable efficacy and safety compared with conventional manual suctioning in mechanically ventilated patients with pneumonia.

Comparing the safety and effectiveness of overlapping stents with flow diverters for unruptured vertebral artery dissecting aneurysms.

BACKGROUND: Endovascular treatment for vertebral artery dissecting aneurysms (VADAs) includes overlapping stents and flow diverters. This study compared the safety and effectiveness of overlapping stents and flow diverters for unruptured VADAs. METHODS: We retrospectively enrolled patients with unruptured VADAs who underwent overlapping stents or flow diverters at two tertiary hospitals in South Korea. The primary clinical outcome was the occurrence of stroke. The primary angiographic outcomes (>12 months) were categorized as regression, no decrease in size, recanalization, or stent occlusion, of which only regression was defined as a favorable angiographic outcomes. RESULTS: Of the 146 patients with VADAs, 25 (17.1%) had flow diverters and 121 (82.9%) had overlapping stents. For the primary angiographic outcomes over 12 months, the rate of favorable angiographic outcomes for flow diverters was 81.8% and for overlapping stents (triple stents) was 98.8% (P=0.006). In the multivariale analysis, after adjusting for partially thrombosed aneurysms, aneurysm shape, non-dominant vessel, posterior inferior cerebellar artery involvement, and procedure type, overlapping stents (triple stents) was not associated with favorable angiographic outcomes compared with flow diverters (OR 7.040, 95% CI 0.549 to 90.294; P=0.134), but partially thrombosed aneurysms was inversely associated with favorable angiographic outcomes (OR 0.056, 95% CI 0.005 to 0.589; P=0.016). The primary clinical outcome followed up to the last angiography did not occur in all patients. CONCLUSION: There was no difference in safety and effectiveness between overlapping stents and flow diverters in unruptured VADAs. Further endovascular treatment studies are needed regarding the association of partially thrombosed aneurysms with unfavorable angiographic outcomes.

Artificial intelligence-based radiographic extent analysis to predict tuberculosis treatment outcomes: a multicenter cohort study.

Predicting outcomes in pulmonary tuberculosis is challenging despite effective treatments. This study aimed to identify factors influencing treatment success and culture conversion, focusing on artificial intelligence (AI)-based chest X-ray analysis and Xpert MTB/RIF assay cycle threshold (Ct) values. In this retrospective study across six South Korean referral centers (January 1 to December 31, 2019), we included adults with rifampicin-susceptible pulmonary tuberculosis confirmed by Xpert assay from sputum samples. We analyzed patient characteristics, AI-based tuberculosis extent scores from chest X-rays, and Xpert Ct values. Of 230 patients, 206 (89.6%) achieved treatment success. The median age was 61 years, predominantly male (76.1%). AI-based radiographic tuberculosis extent scores (median 7.5) significantly correlated with treatment success (odds ratio [OR] 0.938, 95% confidence interval [CI] 0.895-0.983) and culture conversion at 8 weeks (liquid medium: OR 0.911, 95% CI 0.853-0.973; solid medium: OR 0.910, 95% CI 0.850-0.973). Sputum smear positivity was 49.6%, with a median Ct of 26.2. However, Ct values did not significantly correlate with major treatment outcomes. AI-based radiographic scoring at diagnosis is a significant predictor of treatment success and culture conversion in pulmonary tuberculosis, underscoring its potential in personalized patient management.

Machine Learning-Based Etiologic Subtyping of Ischemic Stroke Using Circulating Exosomal microRNAs.

Ischemic stroke is a major cause of mortality worldwide. Proper etiological subtyping of ischemic stroke is crucial for tailoring treatment strategies. This study explored the utility of circulating microRNAs encapsulated in extracellular vesicles (EV-miRNAs) to distinguish the following ischemic stroke subtypes: large artery atherosclerosis (LAA), cardioembolic stroke (CES), and small artery occlusion (SAO). Using next-generation sequencing (NGS) and machine-learning techniques, we identified differentially expressed miRNAs (DEMs) associated with each subtype. Through patient selection and diagnostic evaluation, a cohort of 70 patients with acute ischemic stroke was classified: 24 in the LAA group, 24 in the SAO group, and 22 in the CES group. Our findings revealed distinct EV-miRNA profiles among the groups, suggesting their potential as diagnostic markers. Machine-learning models, particularly logistic regression models, exhibited a high diagnostic accuracy of 92% for subtype discrimination. The collective influence of multiple miRNAs was more crucial than that of individual miRNAs. Additionally, bioinformatics analyses have elucidated the functional implications of DEMs in stroke pathophysiology, offering insights into the underlying mechanisms. Despite limitations like sample size constraints and retrospective design, our study underscores the promise of EV-miRNAs coupled with machine learning for ischemic stroke subtype classification. Further investigations are warranted to validate the clinical utility of the identified EV-miRNA biomarkers in stroke patients.

Assessment of traumatic mandibular nerve using MR neurography sequence: a preliminary study.

BACKGROUND: Iatrogenic mandibular nerve damage resulting from oral surgeries and dental procedures is painful and a formidable challenge for patients and oral surgeons alike, mainly because the absence of objective and quantitative methods for diagnosing nerve damage renders treatment and compensation ambiguous while often leading to medico-legal disputes. The aim of this study was to examine discriminating factors of traumatic mandibular nerve within a specific magnetic resonance imaging (MRI) protocol and to suggest tangible diagnostic criteria for peripheral trigeminal nerve injury. METHODS: Twenty-six patients with ipsilateral mandibular nerve trauma underwent T2 Flex water, 3D short tau inversion recovery (STIR), and diffusion-weighted imaging (DWI) acquired by periodically rotating overlapping parallel lines with enhanced reconstruction (PROPELLER) pulse sequences; 26 injured nerves were thus compared with contra-lateral healthy nerves at anatomically corresponding sites. T2 Flex apparent signal to noise ratio (FSNR), T2 Flex apparent nerve-muscle contrast to noise ratio (FNMCNR) 3D STIR apparent signal to noise ratio (SSNR), 3D STIR apparent nerve-muscle contrast to noise ratio (SNMCNR), apparent diffusion coefficient (ADC) and area of cross-sectional nerve (Area) were evaluated. RESULTS: Mixed model analysis revealed FSNR and FNMCNR to be the dual discriminators for traumatized mandibular nerve (p < 0.05). Diagnostic performance of both parameters was also determined with area under the receiver operating characteristic curve (AUC for FSNR = 0.712; 95% confidence interval [CI]: 0.5660, 0.8571 / AUC for FNMCNR = 0.7056; 95% confidence interval [CI]: 1.011, 1.112). CONCLUSIONS: An increase in FSNR and FNMCNR within our MRI sequence seems to be accurate indicators of the presence of traumatic nerve. This prospective study may serve as a foundation for sophisticated model diagnosing trigeminal nerve trauma within large patient cohorts.

Synchronous occurrence of oral squamous cell carcinoma and Warthin's tumor: systematic review and case report.

We systematically reviewed the literature on the co-occurrence of squamous cell carcinoma (SCC) and Warthin's tumor (WT), thought to be quite rare, to help reduce misdiagnosis and improve treatment planning. For this systematic review, we searched for articles in the Web of Science and PubMed databases, analyzed relevant studies for forward and backward citations, and identified only articles reporting on the "co-occurrence" of WT and SCC. Of the 237 studies identified, 12 comprising 18 patients met the inclusion criteria, to which we added one study from our institution. Most WTs were associated with SCC in the parotid gland or cervical lymph nodes. Most patients (89.5%) underwent selective or radical neck dissection due to identification of lesions separate from the primary SCC. Despite its frequent co-occurrence with other neoplasms, WT in the parotid or cervical lymph nodes tends to be misdiagnosed as a metastatic node when SCC is observed as the primary tumor. Factors to consider in diagnosis and neck management include identification of an association other than growth or development by lymphangiogenesis and whether the patient is a smoker, a strong risk factor.

Association of Body Composition Changes with the Development of Diabetes Mellitus: A Nation-Wide Population Study.

Background: We investigated the association between body composition changes and new-onset diabetes mellitus (DM) development according to the body mass index (BMI) in a longitudinal setting in the general Korean population. Methods: From 2010 to 2011 (1st) and 2012 to 2013 (2nd), we included 1,607,508 stratified random sample participants without DM from the National Health Insurance Service-Health Screening dataset of Korean. The predicted appendicular skeletal muscle mass index (pASMMI), body fat mass index (pBFMI), and lean body mass index (pLBMI) were calculated using pre-validated anthropometric prediction equations. A prediction equation was constructed by combining age, weight, height, waist circumference, serum creatinine levels, alcohol consumption status, physical activity, and smoking history as variables affecting body composition. Results: Decreased pASMMI (men: hazard ratio [HR], 0.866; 95% confidence interval [CI], 0.830 to 0.903; P<0.001; women: HR, 0.748; 95% CI, 0.635 to 0.881; P<0.001), decreased pLBMI (men: HR, 0.931; 95% CI, 0.912 to 0.952; P<0.001; women: HR, 0.906; 95% CI, 0.856 to 0.959; P=0.007), and increased pBFMI (men: HR, 1.073; 95% CI, 1.050 to 1.096; P<0.001; women: HR, 1.114; 95% CI, 1.047 to 1.186; P=0.007) correlated with the development of new-onset DM. Notably, only in the overweight and obese BMI categories, decreases in pASMMI and pLBMI and increases in pBFMI associated with new-onset DM, regardless of gender. Conclusion: Decreased pASMMI and pLBMI, and increased pBFMI with excess fat accumulation may enhance the risk of newonset DM. Therefore, appropriate changes in body composition can help prevent new-onset DM.

Global intracranial arterial tortuosity is associated with intracranial atherosclerotic burden.

The effect of arterial tortuosity on intracranial atherosclerosis (ICAS) is not well understood. This study aimed to evaluate the effect of global intracranial arterial tortuosity on intracranial atherosclerotic burden in patients with ischemic stroke. We included patients with acute ischemic stroke who underwent magnetic resonance angiography (MRA) and classified them into three groups according to the ICAS burden. Global tortuosity index (GTI) was defined as the standardized mean curvature of the entire intracranial arteries, measured by in-house vessel analysis software. Of the 516 patients included, 274 patients had no ICAS, 140 patients had a low ICAS burden, and 102 patients had a high ICAS burden. GTI increased with higher ICAS burden. After adjustment for age, sex, vascular risk factors, and standardized mean arterial area, GTI was independently associated with ICAS burden (adjusted odds ratio [adjusted OR] 1.33; 95% confidence interval [CI] 1.09-1.62). The degree of association increased when the arterial tortuosity was analyzed limited to the basal arteries (adjusted OR 1.48; 95% CI 1.22-1.81). We demonstrated that GTI is associated with ICAS burden in patients with ischemic stroke, suggesting a role for global arterial tortuosity in ICAS.

Improvement in Health-Related Quality of Life Following Antibiotic Treatment in Nontuberculous Mycobacterial Pulmonary Disease: Initial Analysis of the NTM-KOREA Cohort.

BACKGROUND: Improving health-related quality of life (HRQOL) has emerged as a priority in the management of nontuberculous mycobacterial pulmonary disease (NTM-PD). We aimed to evaluate HRQOL and its changes after 6 months' treatment in patients with NTM-PD. METHODS: The NTM-KOREA is a nationwide prospective cohort enrolling patients initiating treatment for NTM-PD in 8 institutions across South Korea. We conducted the Quality of Life-Bronchiectasis (QOL-B) at 6-month intervals and evaluated baseline scores (higher scores indicate better quality of life) and changes after 6 months' treatment. Multivariate logistic regression was performed to identify factors associated with improvement in the QOL-B physical functioning and respiratory symptoms domains. RESULTS: Between February 2022 and August 2023, 411 patients were included in the analysis. Baseline scores (95% confidence interval [CI]) for physical functioning and respiratory symptoms were 66.7 (46.7-86.7) and 81.5 (70.4-92.6), respectively. Among 228 patients who completed the QOL-B after 6 months' treatment, improvements in physical functioning and respiratory symptoms were observed in 61 (26.8%) and 71 (31.1%) patients, respectively. A lower score (adjusted odds ratio; 95% CI) for physical functioning (0.93; 0.91-0.96) and respiratory symptoms (0.92; 0.89-0.95) at treatment initiation was associated with a greater likelihood of physical functioning and respiratory symptom improvement, respectively; achieving culture conversion was not associated with improvement in physical functioning (0.62; 0.28-1.39) or respiratory symptoms (1.30; 0.62-2.74). CONCLUSIONS: After 6 months of antibiotic treatment for NTM-PD, HRQOL improved in almost one-third, especially in patients with severe initial symptoms, regardless of culture conversion. CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov identifier: NCT03934034.

Uncovering the impact of UV radiation on mitochondria in dermal cells: a STED nanoscopy study.

Mitochondria are essential organelles in cellular energy metabolism and other cellular functions. Mitochondrial dysfunction is closely linked to cellular damage and can potentially contribute to the aging process. The purpose of this study was to investigate the subcellular structure of mitochondria and their activities in various cellular environments using super-resolution stimulated emission depletion (STED) nanoscopy. We examined the morphological dispersion of mitochondria below the diffraction limit in sub-cultured human primary skin fibroblasts and mouse skin tissues. Confocal microscopy provides only the overall morphology of the mitochondrial membrane and an indiscerptible location of nucleoids within the diffraction limit. Conversely, super-resolution STED nanoscopy allowed us to resolve the nanoscale distribution of translocase clusters on the mitochondrial outer membrane and accurately quantify the number of nucleoids per cell in each sample. Comparable results were obtained by analyzing the translocase distribution in the mouse tissues. Furthermore, we precisely and quantitatively analyzed biomolecular distribution in nucleoids, such as the mitochondrial transcription factor A (TFAM), using STED nanoscopy. Our findings highlight the efficacy of super-resolution fluorescence imaging in quantifying aging-related changes on the mitochondrial sub-structure in cells and tissues.

Non-pharmacological Treatment for Nontuberculous Mycobacterial Pulmonary Disease.

Nontuberculous mycobacterial pulmonary disease (NTM-PD) arises from the exposure of susceptible hosts to a diverse group of environmental mycobacteria. The emphasis on non-pharmacological strategies is motivated by widespread presence of nontuberculous mycobacteria (NTM) in various environments and the inconsistent success rates of pharmacological treatments. Modifiable factors contributing to NTM-PD development include impaired airway clearance, low body mass index, gastroesophageal reflux disease, and exposure to NTM habitats. This suggests that lifestyle and environmental modifications could affect disease development and progression. The review highlights several modalities that can modify the risk factors. Airway clearance techniques, informed by the "gel-on-brush" model of the bronchial epithelium, aims at enhancing mucociliary clearance and have potential in alleviating symptoms and potentially improving lung function. The impact of nutritional status is also examined, with a lower body mass index linked to an increased risk and progression of NTM-PD, indicating the importance of targeted nutritional support. Additionally, the theoretical and epidemiological links between gastroesophageal reflux disease and NTM-PD advocates for careful management of reflux episodes. Understanding the risk of NTM transmission through environmental exposure to contaminated water and soil is also crucial. Strategies to mitigate this risk, including effective water management and minimizing soil contact, are presented as vital preventive measures. In conclusion, the review supports the inclusion of non-pharmacological treatments within a comprehensive NTM-PD management strategy, alongside conventional pharmacological therapies. This integrated approach seeks to improve the overall understanding and handling of NTM-PD.

High-κ Dielectric (HfO2)/2D Semiconductor (HfSe2) Gate Stack for Low-Power Steep-Switching Computing Devices.

Herein, a high-quality gate stack (native HfO2 formed on 2D HfSe2) fabricated via plasma oxidation is reported, realizing an atomically sharp interface with a suppressed interface trap density (Dit ≈ 5 × 1010 cm-2 eV-1). The chemically converted HfO2 exhibits dielectric constant, κ ≈ 23, resulting in low gate leakage current (≈10-3 A cm-2) at equivalent oxide thickness ≈0.5 nm. Density functional calculations indicate that the atomistic mechanism for achieving a high-quality interface is the possibility of O atoms replacing the Se atoms of the interfacial HfSe2 layer without a substitution energy barrier, allowing layer-by-layer oxidation to proceed. The field-effect-transistor-fabricated HfO2/HfSe2 gate stack demonstrates an almost ideal subthreshold slope (SS) of ≈61 mV dec-1 (over four orders of IDS) at room temperature (300 K), along with a high Ion/Ioff ratio of ≈108 and a small hysteresis of ≈10 mV. Furthermore, by utilizing a device architecture with separately controlled HfO2/HfSe2 gate stack and channel structures, an impact ionization field-effect transistor is fabricated that exhibits n-type steep-switching characteristics with a SS value of 3.43 mV dec-1 at room temperature, overcoming the Boltzmann limit. These results provide a significant step toward the realization of post-Si semiconducting devices for future energy-efficient data-centric computing electronics.

Edoxaban for the treatment of hypercoagulability and cerebral thromboembolism associated with cancer: A randomized clinical trial of biomarker targets.

BACKGROUND: This study aimed compare efficacy of edoxaban and enoxaparin upon biomarkers of hypercoagulability in patients with cancer-related embolic stroke of undetermined source (ESUS). METHODS: In this open-label, randomized, pilot trial, patients with cancer-related ESUS within 30 days of diagnosis were randomly assigned (1:1) to receive edoxaban (60 mg once daily) or enoxaparin (1 mg/kg twice daily) for 90 days. The primary endpoint was interval change of serum D-dimer level between days 0 and 7. The secondary endpoints were microembolic signals detected by transcranial Doppler at 7 and 90 days, the modified Rankin scale score, and stroke recurrence during 90 days. Safety outcomes included major bleeding and all-cause death at 90 days. RESULTS: Of 303 patients with ischemic stroke and cancer, 40 fully met enrollment criteria and were randomized. Baseline D-dimer levels were numerically higher in the edoxaban group (22.9 ± 15.9 µg/mL vs 16.9 ± 16.9 µg/mL). D-dimer level change (%) between days 0 and 7 was similar in the two groups (53.2 ± 25.7 vs 52.2 ± 52.0; P = 0.11). Microembolic signals were detected in 41.1% and 43.8% at baseline, 41.2% and 42.9% at day 7, and 25.0% and 28.6% at day 90 in the edoxaban and enoxaparin groups, respectively. Non-significantly higher major bleeding (35.0% vs 10.0%, P = 0.06) and 90-day mortality (40.0% vs 25.0%, P = 0.31) were noted in the edoxaban group. CONCLUSION: Edoxaban and enoxaparin were comparable with respect to the biomarkers of hypercoagulability and cerebral thromboembolism. Larger trials are warranted to compare effects of edoxaban and enoxaparin upon recurrent stroke and major bleeding in patients with cancer-related ESUS. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT03570281 (https://clinicaltrials.gov/ct2/show/NCT03570281).

Association of body composition indices with cardiovascular outcomes: a nationwide cohort study.

BACKGROUND: Previous studies regarding BMI (kg/m2) and associated cardiovascular outcomes yield inconsistent results. OBJECTIVES: We aimed to investigate the association between body composition and cardiovascular outcomes according to BMI categories in the Korean general population. METHODS: A total of 2,604,401 participants were enrolled in this nationwide cohort study using the National Health Insurance Service-Health Checkup data set. Predicted lean BMI (pLBMI), body fat mass index (pBFMI), and appendicular skeletal muscle mass index (pASMMI) were calculated using validated anthropometric prediction equations. A multivariable time-dependent Cox regression analysis was conducted to assess the association with cardiovascular outcomes. The results were presented with adjusted hazard ratios (HRs) with 95% confidence intervals (CIs), considering BMI categories (BMI < 18.5, BMI 18.5-24.9, BMI 25-29.9, and BMI ≥ 30). RESULTS: Higher pLBMI and pASMMI were correlated with a reduced risk of composite cardiovascular outcomes. For pLBMI, HR was 0.910 (95% CI: 0.908, 0.913, P < 0.001) for males and 0.905 (95% CI: 0.899, 0.910, P < 0.001) for females. For pASMMI, HR was 0.825 (95% CI: 0.820, 0.829, P < 0.001) for males and 0.788 (95% CI: 0.777, 0.800, P < 0.001) for females. Conversely, a higher pBFMI was associated with an increased risk, with HR of 1.082 (95% CI: 1.071, 1.093, P < 0.001) for males and 1.181 (95% CI: 1.170, 1.192, P < 0.001) for females. Subgroup analysis based on BMI categories revealed no significant risk association for pBFMI in the BMI < 18.5 group. In the group with BMI ≥ 30, neither pLBMI nor pASMMI demonstrated a significant risk association. CONCLUSIONS: Our results highlight the value of pLBMI, pBFMI, and pASMMI as variables for assessing risk of composite cardiovascular outcomes. The significance of indicators may vary depending on BMI categories.

Investigation on Contact Properties of 2D van der Waals Semimetallic 1T-TiS2/MoS2 Heterojunctions.

Two-dimensional transition metal dichalcogenides (2D TMDCs) are considered promising alternatives to Si as channel materials because of the possibility of retaining their superior electronic transport properties even at atomic body thicknesses. However, the realization of high-performance 2D TMDC field-effect transistors remains a challenge owing to Fermi-level pinning (FLP) caused by gap states and the inherent high Schottky barrier height (SBH) within the metal contact and channel layer. This study demonstrates that high-quality van der Waals (vdW) heterojunction-based contacts can be formed by depositing semimetallic TiS2 onto monolayer (ML) MoS2. After confirming the successful formation of a TiS2/ML MoS2 heterojunction, the contact properties of vdW semimetal TiS2 were thoroughly investigated. With clean interfaces of the TiS2/ML MoS2 heterojunctions, atomic-layer-deposited TiS2 can induce gap-state saturation and suppress FLP. Consequently, compared with conventional evaporated metal electrodes, the TiS2/ML MoS2 heterojunctions exhibit a lower SBH of 8.54 meV and better contact properties. This, in turn, substantially improves the overall performance of the device, including its on-current, subthreshold swing, and threshold voltage. Furthermore, we believe that our proposed strategy for vdW-based contact formation will contribute to the development of 2D materials used in next-generation electronics.