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.

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.

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.

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.

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.

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.

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.

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.

Outcome of Atezolizumab Plus Bevacizumab Combination Therapy in High-Risk Patients with Advanced Hepatocellular Carcinoma.

Real-world data regarding treatment with atezolizumab plus bevacizumab in high-risk patients with advanced HCC are lacking. In this multicenter retrospective cohort study, a total of 215 patients with advanced HCC received atezolizumab plus bevacizumab treatment at four tertiary hospitals. High-risk patients were those with grade Vp4 portal vein thrombus, bile duct invasion, or more than 50% liver infiltration. In total, 98 (45.6%) were the high-risk population, 186 (86.5%) were considered to be Child-Pugh class A, and 128 (59.5%) had previously received neoadjuvant or concomitant radiation treatment. Median overall survival (OS) was 11.25 months (95% CI, 9.50-13.10), and the median progression-free survival (PFS) was 8.00 months (95% CI, 6.82-9.18). In the high-risk population, the median OS was 10 months (95% CI, 8.19-11.82) and the median PFS was 6.50 months (95% CI, 3.93-9.08). In the high-risk population, multivariate analysis indicated that radiation therapy and lower ALBI grade were associated with better OS and PFS. A total of 177 (82.3%) patients experienced adverse events of any grade, the most common being proteinuria (23.7%). Atezolizumab plus bevacizumab treatment showed consistent efficacy and tolerability in both the total and high-risk population. Radiation therapy combined with atezolizumab plus bevacizumab treatment might be helpful to improve PFS and OS in high-risk populations.

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.

Evaluation of peripheral nerve injury according to the severity of damage using 18F-FDG PET/MRI in a rat Model of sciatic nerve injury.

OBJECTIVES: We ascertained that the PET scan may be a valuable imaging modality for the noninvasive, objective diagnosis of neuropathic pain caused by peripheral nerve injury through the previous study. This study aimed to assess peripheral nerve damage according to severity using18F-FDG PET/MRI of the rat sciatic nerve. METHODS: Eighteen rats were divided into three groups: 30-second (G1), 2-minute (G2), and 5-minute (G3) crushing injuries. The severity of nerve damage was measured in the third week after the crushing injury using three methods: the paw withdrawal threshold test (RevWT), standardized uptake values on PET (SUVR), and intensity analysis on immunohistochemistry (IntR). RESULTS: There were significant differences between G1 and G3 in both SUVR and IntR (p = 0.012 and 0.029, respectively), and no significant differences in RevWT among the three groups (p = 0.438). There was a significant difference in SUVR (p = 0.012), but no significant difference in IntR between G1 and G2 (p = 0.202). There was no significant difference between G2 and G3 in SUVR and IntR (p = 0.810 and 0.544, respectively). DISCUSSION: Although PET did not show results consistent with those of immunohistochemistry in all respects, this study demonstrated that PET uptake tended to increase with severe nerve damage. If this research is supplemented by further experiments, PET/MRI can be used as an effective diagnostic modality.

Understanding the effects of Haemophilus influenzae colonization on bronchiectasis: a retrospective cohort study.

BACKGROUND: Bacterial colonization is an essential aspect of bronchiectasis. Although Haemophilus influenzae is a frequent colonizer in some regions, its clinical impacts are poorly understood. This study aimed to elucidate the impact of H. influenzae colonization in patients with bronchiectasis. METHODS: This retrospective study screened adult patients diagnosed with bronchiectasis at a tertiary referral center between April 1, 2003, and May 16, 2021, in South Korea. Propensity score matching was used to match patients with and without H. influenzae colonization. We assessed the severity of bronchiectasis as per the bronchiectasis severity index, the incidence of exacerbation, differences in lung function, and all-cause mortality. RESULTS: Out of the 4,453 patients with bronchiectasis, 79 (1.8%) were colonized by H. influenzae. After 1:2 propensity score matching, 78 and 154 patients were selected from the H. influenzae colonizer and non-colonizer groups, respectively. Although there were no significant differences between the groups regarding baseline demographics, patients colonized with H. influenzae had a higher bronchiectasis severity index (median 6 [interquartile range 4-8] vs. 4 [2-7], p = 0.002), associated with extensive radiographic involvement (52.2% vs. 37.2%, p = 0.045) and mild exacerbation without hospitalization (adjusted incidence rate ratio 0.15; 95% confidence interval 0.12-0.24). Lung function and mortality rates did not reveal significant differences, regardless of H. influenzae colonization. CONCLUSION: H. influenzae colonization in bronchiectasis was associated with more severe disease and greater incidence of mild exacerbation, but not lung function and mortality. Attention should be paid to patients with bronchiectasis with H. influenzae colonization.

Identification and characterization of novel ERBB4 variant associated with sporadic amyotrophic lateral sclerosis (ALS).

Amyotrophic Lateral Sclerosis (ALS) is the most common type of motor neuron disease characterized by progressive motor neuron degeneration in brain and spinal cord. Most cases are sporadic in ALS and 5-10% of cases are familiar. >50 genes are known to be associated with ALS and one of them is ERBB4. In this paper, we report the case of a 53-year-old ALS patient with progressive muscle weakness and fasciculation, but he had no cognitive decline. We performed the next generation sequencing (NGS) and in silico analysis, it predicted a highly pathogenic variant, c.2116 A > G, p.Asn706Asp (N706D) in the ERBB4 gene. The amino acid residue is highly conserved among species. ERBB4 is a member of the ERBB family of receptor tyrosine kinases. ERBB4 has multiple tyrosine phosphorylation sites, including an autophosphorylation site at tyrosine 1284 residue. Autophosphorylation of ERBB4 promotes biological activity and it associated with NRG-1/ERBB4 pathway. It is already known that tyrosine 128 phosphorylation of ERBB4 is decreased in patients who have ALS-associated ERBB4 mutations. We generated ERBB4 N706D construct using site-directed mutagenesis and checked the phosphorylation level of ERBB4 N706D in NSC-34 cells. We found that the phosphorylation of ERBB4 N706D was decreased compared to ERBB4 wild-type, indicating a loss of function mutation in ERBB4. We report a novel variant in ERBB4 gene leading to ALS through dysfunction of ERBB4.

Post-treatment Radiographic Severity and Mortality in Mycobacterium avium Complex Pulmonary Disease.

Rationale: Imaging studies are widely performed when treating Mycobacterium avium complex pulmonary disease (MAC-PD); however, the clinical significance of post-treatment radiographic change is unknown. Objectives: To determine whether a deep neural network trained with pulmonary tuberculosis could adequately score the radiographic severity of MAC-PD and then to examine relationships between post-treatment radiographic severity and its change from baseline and long-term prognosis. Methods: We retrospectively collected chest radiographs of adult patients with MAC-PD treated for ⩾6 months at baseline and at 3, 6, 9, and 12 months of treatment. We correlated the radiographic severity score generated by a deep neural network with visual and clinical severity as determined by radiologists and mycobacterial culture status, respectively. The associations between the score, improvement from baseline, and mortality were analyzed using Cox proportional hazards regression. Results: In total, 342 and 120 patients were included in the derivation and validation cohorts, respectively. The network's severity score correlated with radiologists' grading (Spearman coefficient, 0.40) and mycobacterial culture results (odds ratio, 1.02; 95% confidence interval [CI], 1.0-1.05). A significant decreasing trend in the severity score was observed over time (P < 0.001). A higher score at 12 months of treatment was independently associated with higher mortality (adjusted hazard ratio, 1.07; 95% CI, 1.03-1.10). Improvements in radiographic scores from baseline were associated with reduced mortality, regardless of culture conversion (adjusted hazard ratio, 0.42; 95% CI, 0.22-0.80). These findings were replicated in the validation cohort. Conclusions: Post-treatment radiographic severity and improvement from baseline in patients with MAC-PD were associated with long-term survival.