The risk of open angle glaucoma in young adults with allergic diseases: a Nationwide cohort study.

This study investigated the potential associations between allergic diseases (asthma, allergic rhinitis, and atopic dermatitis) and the development of primary open-angle glaucoma. We utilized authorized data from the Korean National Health Information Database (KNHID), which provides comprehensive medical claims data and information from the National Health Screening Program. We compared the baseline characteristics of subjects with and without allergic diseases and calculated the incidence and risk of glaucoma development. Cox proportional hazard regression analysis was used to determine the risk of glaucoma development in subjects with allergic diseases. A total of 171,129 subjects aged 20-39 with or without allergic diseases who underwent a general health examination between 2009 and 2015 were included. Subjects with allergic diseases exhibited a higher incidence of glaucoma compared to the control group. The hazard ratio (HR) of glaucoma onset was 1.49 and 1.39 in subjects with at least one allergic disease before and after adjusting for potential confounding factors, respectively. Among allergic diseases, atopic dermatitis showed the highest risk for glaucoma development (aHR 1.73) after adjusting for confounders. Allergic rhinitis showed an increased risk for incident glaucoma after adjustment (aHR 1.38). Asthma showed the lowest but still increased risk for glaucoma (aHR 1.22). The associations were consistent in all subgroup analyses stratified by sex, smoking, drinking, exercise, diabetes, hypertension, dyslipidemia, or history of steroid. In conclusion, allergic diseases are associated with increased risk of glaucoma development. Among allergic diseases, atopic dermatitis showed the highest risk for glaucoma development followed by allergic rhinitis and asthma.

Importance of multimodal resident education curriculum for general surgeons: perspectives of trainers and trainees.

PURPOSE: Satisfaction should be prioritized to maximize the value of education for trainees. This study was conducted with professors, fellows, and surgical residents in the Department of general surgery (GS) to evaluate the importance of various educational modules to surgical residents. METHODS: A questionnaire was administered to professors (n = 28), fellows (n = 8), and surgical residents (n = 14), and the responses of the three groups were compared. Four different categories of educational curricula were considered: instructor-led training, clinical education, self-paced learning, and hands-on training. RESULTS: The majority of surgeons regarded attending scrubs as the most important educational module in the training of surgical residents. However, while professors identified assisting operators by participating in surgery as the most important, residents assessed the laparoscopic training module with animal models as the most beneficial. CONCLUSIONS: The best educational training course for surgical residents was hands-on training, which would provide them with several opportunities to operate and perform surgical procedures themselves.

Genomic insights into inherited bone marrow failure syndromes in a Korean population.

Inherited bone marrow failure syndromes (IBMFS) pose significant diagnostic challenges due to overlapping symptoms and variable expressivity, despite evolving genomic insights. The study aimed to elucidate the genomic landscape among 130 Korean patients with IBMFS. We conducted targeted next-generation sequencing (NGS) and clinical exome sequencing (CES) across the cohort, complemented by whole genome sequencing (WGS) and chromosomal microarray (CMA) in 12 and 47 cases, respectively, with negative initial results. Notably, 50% (n = 65) of our cohort achieved a genomic diagnosis. Among these, 35 patients exhibited mutations associated with classic IBMFSs (n = 33) and the recently defined IBMFS, aplastic anaemia, mental retardation and dwarfism syndrome (AmeDS, n = 2). Classic IBMFSs were predominantly detected via targeted NGS (85%, n = 28) and CES (88%, n = 29), whereas AMeDS was exclusively identified through CES. Both CMA and WGS aided in identifying copy number variations (n = 2) and mutations in previously unexplored regions (n = 2). Additionally, 30 patients were diagnosed with other congenital diseases, encompassing 13 distinct entities including inherited thrombocytopenia (n = 12), myeloid neoplasms with germline predisposition (n = 8), congenital immune disorders (n = 7) and miscellaneous genomic conditions (n = 3). CES was particularly effective in revealing these diverse diagnoses. Our findings underscore the significance of comprehensive genomic analysis in IBMFS, highlighting the need for ongoing exploration in this complex field.

Tuberculosis and osteoporotic fracture risk: development of individualized fracture risk estimation prediction model using a nationwide cohort study.

Purpose: Tuberculosis (TB) is linked to sustained inflammation even after treatment, and fracture risk is higher in TB survivors than in the general population. However, no individualized fracture risk prediction model exists for TB survivors. We aimed to estimate fracture risk, identify fracture-related factors, and develop an individualized risk prediction model for TB survivors. Methods: TB survivors (n = 44,453) between 2010 and 2017 and 1:1 age- and sex-matched controls were enrolled. One year after TB diagnosis, the participants were followed-up until the date of fracture, death, or end of the study period (December 2018). Cox proportional hazard regression analyses were performed to compare the fracture risk between TB survivors and controls and to identify fracture-related factors among TB survivors. Results: During median 3.4 (interquartile range, 1.6-5.3) follow-up years, the incident fracture rate was significantly higher in TB survivors than in the matched controls (19.3 vs. 14.6 per 1,000 person-years, p < 0.001). Even after adjusting for potential confounders, TB survivors had a higher risk for all fractures (adjusted hazard ratio 1.27 [95% confidence interval 1.20-1.34]), including hip (1.65 [1.39-1.96]) and vertebral (1.35 [1.25-1.46]) fractures, than matched controls. Fracture-related factors included pulmonary TB, female sex, older age, heavy alcohol consumption, reduced exercise, and a higher Charlson Comorbidity Index (p < 0.05). The individualized fracture risk model showed good discrimination (concordance statistic = 0.678). Conclusion: TB survivors have a higher fracture risk than matched controls. An individualized prediction model may help prevent fractures in TB survivors, especially in high-risk groups.

Attenuating mitochondrial dysfunction and morphological disruption with PT320 delays dopamine degeneration in MitoPark mice.

BACKGROUND: Mitochondria are essential organelles involved in cellular energy production. Changes in mitochondrial function can lead to dysfunction and cell death in aging and age-related disorders. Recent research suggests that mitochondrial dysfunction is closely linked to neurodegenerative diseases. Glucagon-like peptide-1 receptor (GLP-1R) agonist has gained interest as a potential treatment for Parkinson's disease (PD). However, the exact mechanisms responsible for the therapeutic effects of GLP-1R-related agonists are not yet fully understood. METHODS: In this study, we explores the effects of early treatment with PT320, a sustained release formulation of the GLP-1R agonist Exenatide, on mitochondrial functions and morphology in a progressive PD mouse model, the MitoPark (MP) mouse. RESULTS: Our findings demonstrate that administration of a clinically translatable dose of PT320 ameliorates the reduction in tyrosine hydroxylase expression, lowers reactive oxygen species (ROS) levels, and inhibits mitochondrial cytochrome c release during nigrostriatal dopaminergic denervation in MP mice. PT320 treatment significantly preserved mitochondrial function and morphology but did not influence the reduction in mitochondria numbers during PD progression in MP mice. Genetic analysis indicated that the cytoprotective effect of PT320 is attributed to a reduction in the expression of mitochondrial fission protein 1 (Fis1) and an increase in the expression of optic atrophy type 1 (Opa1), which is known to play a role in maintaining mitochondrial homeostasis and decreasing cytochrome c release through remodeling of the cristae. CONCLUSION: Our findings suggest that the early administration of PT320 shows potential as a neuroprotective treatment for PD, as it can preserve mitochondrial function. Through enhancing mitochondrial health by regulating Opa1 and Fis1, PT320 presents a new neuroprotective therapy in PD.

ERBB2 Targeting Reveals a Significant Suppression of Tumorigenesis in Murine Endometrial Cancer with Pten Mutation.

Endometrial cancer is the most common gynecologic malignancy. PTEN is a negative regulator of PI3K signaling and is deficient in > 50% of primary human endometrial cancer. Amplification of ERBB2 promotes tumorigenesis and pathogenesis of several human cancers. However, the effect of ERBB2 targeting has not been studied in endometrial cancer with PTEN mutations. The murine model Pgrcre/+Erbb2f/fPtenf/f (Erbb2d/d Ptend/d) was developed to evaluate the effect of ERBB2 targeted therapy in endometrial cancer with PTEN deficiency. Histopathological and molecular analysis was performed for Ptend/d and Erbb2d/dPtend/d mice. Histopathological analysis revealed that Erbb2d/dPtend/d mice significantly reduced development and progression of endometrial cancer compared to Ptend/d mice. Furthermore, percentage of proliferative cells in Erbb2d/dPtend/d mice revealed anti-tumorigenic effect of Erbb2 ablation compared to Ptend/d mice. Our results demonstrate that Erbb2 ablation reveals a significant suppression of tumorigenesis on endometrial cancer of Ptend/d mice. Our results suggest that Erbb2 functions as an oncogene in endometrial cancer of Ptend/d mice implying that Erbb2 targeting can be used as an effective therapeutic approach for treatment of endometrial cancer with PTEN deficiency to hinder cancer development.

Association of physical activity with fractures in kidney transplant recipients: A Korean nationwide cohort study.

Kidney transplant recipients are at high risk for fractures, primarily due to post-transplant bone disease. This retrospective cohort study analyzed data from the Korean National Health Insurance Service, including 10 083 kidney transplant recipients examined from 2009 to 2017. We assessed fracture incidence, emphasizing vertebral and hip fractures, and the association of physical activity and traditional risk factors with fracture risk. Kidney transplant recipients were categorized into three groups according to physical activity levels: non-activity, metabolic equivalent of task (MET) 1-499, and MET ≥500. Physical activity was associated with a decreased risk of all types of fractures: any (MET 1-499: adjusted hazard ratio (aHR) .75; 95% confidence interval (CI) .62-.92, MET ≥500: aHR .84; 95% CI .70-1.00), vertebral (MET 1-499: aHR .69; 95% CI .49-.98, MET ≥500: aHR .67; 95% CI .49-.91), and hip (MET 1-499: aHR .43; 95% CI .23-.81) fractures. Additionally, older age, female sex, and diabetes were associated with an increased fracture risk. The assessment of physical activity and traditional risk factors could improve fracture risk prediction. Our findings emphasize the need for further research to establish optimal physical activity recommendations for fracture prevention in kidney transplant recipients.

Impact of Smoking and Alcohol Consumption on Early-Onset Gastric Cancer Development in Young Koreans: A Population-Based Study.

PURPOSE: Although smoking and alcohol consumption are known risk factors for gastric cancer (GC), studies assessing their effects on early-onset GC are limited. In this nationwide, population-based, prospective cohort study, we assessed the effects of smoking and alcohol consumption on early-onset GC in patients aged <50 years. MATERIALS AND METHODS: We analyzed data of patients aged 20-39 years who underwent cancer and general health screening in the Korean National Health Screening Program between 2009 and 2012. We calculated the adjusted hazard ratios (aHR) and 95% confidence intervals (CI) for GC incidence until December 2020. RESULTS: We enrolled 6,793,699 individuals (men:women=4,077,292:2,716,407) in this cohort. The mean duration of follow-up was 9.4 years. During follow-up, 9,893 cases of GC (men:women=6,304:3,589) were reported. Compared with the aHRs (95% CI) of never-smokers, those of former and current-smokers were 1.121 (1.044-1.205) and 1.282 (1.212-1.355), respectively. Compared with the aHRs (95% CI) of non-consumers, those of low-moderate- and high-risk alcohol consumers were 1.095 (1.046-1.146) and 1.212 (1.113-1.321), respectively. GC risk was the highest in current-smokers and high-risk alcohol consumers (1.447 [1.297-1.615]). Interestingly, alcohol consumption and smoking additively increased the GC risk in men but not in women (Pinteraction=0.002). CONCLUSION: Smoking and alcohol consumption are significant risk factors for early-onset GC in young Koreans. Further studies are needed to investigate sex-based impact of alcohol consumption and smoking on GC incidence in young individuals.

Effects of Transcutaneous Electrical Nerve Stimulation with Taping on Wrist Spasticity, Strength, and Upper Extremity Function in Patients with Stroke: A Randomized Control Trial.

Objective: Six months after the onset of stroke, over 60% of patients experience upper limb dysfunction, with spasticity being a major contributor alongside muscle weakness. This study investigated the effect of transcutaneous electrical nerve stimulation (TENS) with taping on wrist spasticity, strength, and upper extremity function in patients with stroke. Methods: In total, 40 patients with stroke were included and randomly divided into two groups: the TENS + taping (n = 20, age 52.4 ± 9.3 (range: 39 to 70)) and TENS (n = 20, age 53.5 ± 10.8 (range: 39 to 74)) groups. All subjects performed 30 sessions of task-related training, which included 10 min of postural control training and 20 min of task performance. Additionally, all subjects received TENS on the spastic muscle belly for 30 min before task-related training. In the TENS + taping group, taping was additionally applied to the forearm and wrist but not in the TENS group. The Modified Ashworth Scale was used to measure spasticity, and a handheld dynamometer was used to measure muscle strength. The Fugl-Meyer Assessment of Upper Extremity was used to evaluate the functional ability of the upper extremity. Results: In the TENS + taping group, spasticity and upper extremity function were significantly improved as compared to those in the TENS group (p < 0.05). However, no significant difference in muscle strength was observed between the two groups (p > 0.05). Conclusions: This study demonstrated that the combination of TENS and taping for spasticity and function of the upper extremity was more effective in relieving the spasticity than TENS alone. Therefore, we suggest this combination as an additional treatment for spasticity and function of the upper extremity.

Incidentally found parotid gland lesion in 18F-FDG PET/CT for staging evaluation of patients with hepatocellular carcinoma: remote possibility of metastatic tumor or second primary salivary gland malignancy.

OBJECTIVES: We primarily aimed to evaluate whether parotid incidental lesion (PIL) in 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) for staging evaluation of patients with hepatocellular carcinoma (HCC) would represent a possibility of extrahepatic metastasis or second primary malignancy (SPM). Additionally, we explored the incidence of PIL in HCC patients and examined any associated risk factors. METHODS: We retrospectively analyzed patients with HCC who underwent 18F-FDG PET/CT at our institution from 2010 to 2022. The pathological findings of PILs in HCC patients were investigated for confirmatory identification of the risk of HCC metastasis or SPM in parotid gland. Healthy controls received 18F-FDG PET/CT for health screening were also enrolled to compare the incidence of PILs with HCC patients. Various parameters associated with patient demographics and characteristics of HCC were analyzed to find the related factors of PILs. RESULTS: A total of 17,674 patients with HCC and 2,090 healthy individuals who had undergone 18F-FDG PET/CT scans were enrolled in the analyses. Among the 54 HCC patients who underwent pathological confirmation for PILs, benign primary parotid tumor was most commonly observed (n = 43 [79.6%]); however, no malignant lesions were detected, including HCC metastasis. The incidence of PILs was higher in patients diagnosed with HCC compared with the control group (485 [2.7%] vs. 23 [1.1%], p = 0.002). Analysis for the risk factors for PILs revealed that patient age, sex, and positive viral markers were significantly associated with the incidence of PILs in patients with HCC (all p < 0.001). CONCLUSIONS: Our study demonstrates that PILs are more frequently identified in patients with HCC on 18F-FDG PET/CT. However, no malignant PIL, including extrahepatic metastasis of HCC, was identified. Therefore, the presence of PIL should not impede or delay the treatment process for patients with HCC. Additionally, we suggested that for future swift and straightforward differential diagnoses of PIL, the development of additional protocols within the PET/CT imaging could be beneficial.

Direct Oral Anticoagulant Use Early After Cardiac Surgery: A Retrospective Cohort Study.

Background: There is limited literature guiding the prescribing of direct oral anticoagulants (DOACs) early after cardiac surgery as this population has been excluded from landmark randomized controlled trials. This study aims to determine the rate of in-hospital DOAC use compared with warfarin early after cardiac surgery, evaluate factors associated with DOAC use, determine difference in postoperative length of stay, and characterize bleeding events. Methods: A retrospective cohort study was conducted in adult patients with indications for anticoagulation and receiving either a DOAC or warfarin after cardiac surgery during their index hospitalization. Patients were excluded if they had any contraindications to DOAC use. The primary outcome was the proportion of patients discharged on a DOAC compared with warfarin. Results: Of included 210 patients, 30% received DOACs and 70% received warfarin on discharge. The most common DOAC used was apixaban (74.6%), and median postoperative day of initiation was 5 days. Patients receiving DOACs were older (70.8 vs 68.0 years), had less valvular heart disease (38.1% vs 63.9%), were more likely to be on DOACs preoperatively (50.8% vs 31.3%), and were more likely to have undergone coronary artery bypass graft alone (54.0% vs 24.5%) compared with those on warfarin. Postoperative length of stay (7 vs 9 days; P = 0.59) and in-hospital bleeding (1.6% vs 2.0%; P = 1.00) did not differ between DOAC and warfarin groups. Conclusions: At a quaternary referral centre for cardiac surgery, DOACs were used in approximately one-third of patients with an indication for anticoagulation early after cardiac surgery.

Introduction: Il existe peu de documentation sur la prescription des anticoagulants oraux directs (AOC) peu de temps après la chirurgie cardiaque puisque cette population a été exclue des essais cliniques novateurs à répartition aléatoire. La présente étude vise à déterminer le taux d'utilisation des AOC à l'hôpital par rapport au taux d'utilisation de la warfarine peu de temps après la chirurgie cardiaque, à évaluer les facteurs associés à l'utilisation des AOC, à déterminer l'écart de la durée du séjour et à caractériser les événements hémorragiques. Méthodes: Nous avons réalisé une étude de cohorte rétrospective auprès de patients adultes qui avaient des indications d'anticoagulation et qui recevaient des AOC ou de la warfarine après la chirurgie cardiaque durant l'hospitalisation de référence. Les patients étaient exclus s'ils avaient des contre-indications à l'utilisation des AOC. Le critère d'évaluation principal était la proportion de patients sortis de l'hôpital sous AOC par rapport à celle des patients sortis de l'hôpital sous warfarine. Résultats: Parmi les 210 patients inclus, 30 % ont reçu des AOC et 70 % ont reçu de la warfarine à la sortie de l'hôpital. L'AOC le plus fréquemment utilisé était l'apixaban (74,6 %), et le nombre médian de jours après l'intervention chirurgicale du début du traitement était 5 jours. Les patients qui recevaient les AOC étaient plus âgés (70,8 vs 68,0 ans), avaient moins de cardiopathies valvulaires (38,1 % vs 63,9 %), étaient plus susceptibles de recevoir des AOC avant l'opération (50,8 % vs 31,3 %) et étaient plus susceptibles d'avoir seulement subi un pontage aorto-coronarien (54,0 % vs 24,5 %) que ceux sous warfarine. La durée du séjour postopératoire (7 vs 9 jours ; P = 0,59) et les événements hémorragiques à l'hôpital (1,6 % vs 2,0 % ; P = 1,00) ne différaient pas entre les groupes qui recevaient les AOC et les groupes qui recevaient la warfarine. Conclusions: Dans un centre d'aiguillage de soins quaternaires en chirurgie cardiaque, les AOC ont été utilisés chez environ un tiers des patients qui avaient une indication d'anticoagulation peu de temps après la chirurgie cardiaque.

Long non-coding RNA SOX2OT in tamoxifen-resistant breast cancer.

Hormone receptor (HR)-positive breast cancer can become aggressive after developing hormone-treatment resistance. This study elucidated the role of long non-coding RNA (lncRNA) SOX2OT in tamoxifen-resistant (TAMR) breast cancer and its potential interplay with the tumor microenvironment (TME). TAMR breast cancer cell lines TAMR-V and TAMR-H were compared with the luminal type A cell line (MCF-7). LncRNA expression was assessed via next-generation sequencing, RNA extraction, lncRNA profiling, and quantitative RT-qPCR. SOX2OT overexpression effects on cell proliferation, migration, and invasion were evaluated using various assays. SOX2OT was consistently downregulated in TAMR cell lines and TAMR breast cancer tissue. Overexpression of SOX2OT in TAMR cells increased cell proliferation and cell invasion. However, SOX2OT overexpression did not significantly alter SOX2 levels, suggesting an independent interaction within TAMR cells. Kaplan-Meier plot analysis revealed an inverse relationship between SOX2OT expression and prognosis in luminal A and B breast cancers. Our findings highlight the potential role of SOX2OT in TAMR breast cancer progression. The downregulation of SOX2OT in TAMR breast cancer indicates its involvement in resistance mechanisms. Further studies should explore the intricate interactions between SOX2OT, SOX2, and TME in breast cancer subtypes.

Risk of depression and anxiety in multiple sclerosis and neuromyelitis optica spectrum disorder: A nationwide cohort study in South Korea.

BACKGROUND: We investigated the risks of depression/anxiety in patients with multiple sclerosis (pwMS) or patients with neuromyelitis optica spectrum disorder (pwNMOSD). OBJECTIVES: MS/NMOSD cohorts were collected from Korean National Health Insurance Service, using the International Classification of Diseases-10th and information on Rare Intractable Disease program. Patients who were younger than 20 years, had a previous depression/anxiety, or died in the index year were excluded. METHODS: Hazard ratios (HRs) of depression/anxiety in pwMS and pwNMOSD from controls matched 1:5 for age, sex, hypertension, diabetes, and dyslipidemia were calculated using Cox regressions with a 1-year lag period and estimated over time. RESULTS: During a mean follow-up of 4.1 years, adjusted hazard ratios (aHR) for depression were 3.25 (95% confidence interval (CI) = 2.59-4.07) in MS and 2.17 (1.70-2.76) in NMOSD, and aHRs for anxiety were 1.83 (1.49-2.23) in MS and 1.56 (1.26-1.91) in NMOSD. The risks of anxiety/depression did not differ between MS and NMOSD and were highest in the second year after diagnosis of MS/NMOSD. The relative risk of depression was higher in younger pwMS/pwNMOSD, and the relative risk of anxiety was higher in pwMS who was male, had low income, or lived in a non-urban area. CONCLUSION: The risk of depression and anxiety was increased in pwMS/pwNMOSD.

Evaluation of Long-Term Adaptive Immune Responses Specific to SARS-CoV-2: Effect of Various Vaccination and Omicron Exposure.

The immune response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) becomes increasingly complex as individuals receive different combinations of vaccine doses and encounter breakthrough infections. Our study focused on the immunogenicity observed over a two-year period in healthy individuals who completed a two-dose series and then experienced booster and/or Omicron infection. In June 2023, we recruited 78 healthcare workers who had previously participated in clinical research initiated in March 2021 at a single medical center in South Korea. At 1, 5, 11, and 25 months after a second dose, we assessed SARS-CoV-2-specific humoral and cellular immune responses. Longitudinal monitoring revealed a significant decline in humoral immunity levels after the second vaccine dose, followed by a substantial increase post-third vaccination or breakthrough infection. In contrast, stable cellular immune responses were consistently observed, with peak humoral and cellular immune measures reached at 25 months after the second dose. Among infection-naïve participants, three-dose vaccinated individuals had decreased neutralizing activity against wild-type (WT) and negative activities against Omicron subvariants BA.2 and BA.4/5, whereas those who received a fourth dose of bivalent BNT had significantly increased neutralizing activity (p < 0.05). All immune metrics tended to increase as the number of vaccine doses increased. Among participants with 4-exposure, homologous vaccination (mRNA × 4) led to higher humoral immunity, whereas heterologous vaccination (ChAd × 2/mRNA × 2) induced stronger cellular responses against multiple SARS-CoV-2 variants by enzyme-linked immunospot assays (p < 0.05). Immune responses from bivalent vaccines or Omicron infection did not show statistically significant differences among exposure number-matched participants (p > 0.05). Omicron exposure significantly increased cross-neutralizing activity, but magnitude of cellular immunity was not significantly altered by Omicron exposure. Our longitudinal study highlights the evolving complexity of SARS-CoV-2 immune responses, showing enhanced immunity with multiple vaccine doses and robust cellular responses from heterologous vaccination. These findings emphasize the need for ongoing surveillance to optimize vaccination strategies against emerging variants.

Targeting the receptor tyrosine kinase MerTK shows therapeutic value in gastric adenocarcinoma.

BACKGROUND: Despite multiple therapeutic modalities, the overall survival of patients with gastric adenocarcinoma remains poor, especially for advanced tumor stages. Although the tyrosine kinase MerTK has shown therapeutic relevance in several tumor entities, its potential effects in gastric adenocarcinoma have not yet been sufficiently characterized. METHODS: MerTK expression and its influence on patient survival were evaluated by immunohistochemistry in a cohort of 140 patients with gastric adenocarcinoma. CRISPR/Cas9 knockout and siRNA knockdown of MerTK in the gastric cancer cell lines SNU1, SNU5, and MKN45 was used to analyze protein expression, growth, migration, and invasion properties in vitro and in a murine xenograft model. MerTK was pharmacologically targeted with the small molecule inhibitor UNC2025 in vitro and in vivo. RESULTS: In patients, high MerTK expression was associated with decreased overall survival (OS) and lymph node metastasis especially in patients without neoadjuvant therapy (p < 0.05). Knockout and knockdown of MerTK reduced cell proliferation and migration both in vitro and in vivo. UNC2025, a small-molecule inhibitor of MerTK, exhibited a significant therapeutic response in vitro and in vivo. Additionally, MerTK expression attenuated the response to neoadjuvant treatment, and its inhibition sensitized tumor cells to 5-Fluorouracil (5-FU)-based chemotherapy in vitro. CONCLUSIONS: Our findings demonstrate the potential value of MerTK as a prognostic biomarker for gastric adenocarcinoma. Targeting MerTK may become a new treatment option, especially for patients with advanced tumors, and may overcome resistance to established chemotherapies.

Reduced Alcohol Consumption and Major Adverse Cardiovascular Events Among Individuals With Previously High Alcohol Consumption.

Importance: Cardiovascular benefits of mild to moderate alcohol consumption need to be validated in the context of behavioral changes. The benefits of reduced alcohol consumption among people who drink heavily across different subtypes of cardiovascular disease (CVD) are unclear. Objective: To investigate the association between reduced alcohol consumption and risk of major adverse cardiovascular events (MACEs) in individuals who drink heavily across different CVD subtypes. Design, Setting, and Participants: This cohort study analyzed data from the Korean National Health Insurance Service-Health Screening database and self-reported questionnaires. The nationally representative cohort comprised Korean citizens aged 40 to 79 years who had national health insurance coverage on December 31, 2002, and were included in the 2002 to 2003 National Health Screening Program. People who drank heavily who underwent serial health examinations over 2 consecutive periods (first period: 2005-2008; second period: 2009-2012) were included and analyzed between February and May 2023. Heavy drinking was defined as more than 4 drinks (56 g) per day or more than 14 drinks (196 g) per week for males and more than 3 drinks (42 g) per day or more than 7 drinks (98 g) per week for females. Exposures: Habitual change in heavy alcohol consumption during the second health examination period. People who drank heavily at baseline were categorized into 2 groups according to changes in alcohol consumption during the second health examination period as sustained heavy drinking or reduced drinking. Main Outcomes and Measures: The primary outcome was the occurrence of MACEs, a composite of nonfatal myocardial infarction or angina undergoing revascularization, any stroke accompanied by hospitalization, and all-cause death. Results: Of the 21 011 participants with heavy alcohol consumption at baseline (18 963 males [90.3%]; mean [SD] age, 56.08 [6.16] years) included in the study, 14 220 (67.7%) sustained heavy drinking, whereas 6791 (32.2%) shifted to mild to moderate drinking. During the follow-up of 162 378 person-years, the sustained heavy drinking group experienced a significantly higher incidence of MACEs than the reduced drinking group (817 vs 675 per 100 000 person-years; log-rank P = .003). Reduced alcohol consumption was associated with a 23% lower risk of MACEs compared with sustained heavy drinking (propensity score matching hazard ratio [PSM HR], 0.77; 95% CI, 0.67-0.88). These benefits were mostly accounted for by a significant reduction in the incidence of angina (PSM HR, 0.70; 95% CI, 0.51-0.97) and ischemic stroke (PSM HR, 0.66; 95% CI, 0.51-0.86). The preventive attributes of reduced alcohol intake were consistently observed across various subgroups of participants. Conclusions and Relevance: Results of this cohort study suggest that reducing alcohol consumption is associated with a decreased risk of future CVD, with the most pronounced benefits expected for angina and ischemic stroke.

Treatment of local recurrence of esophageal cancer following Ivor-Lewis esophagectomy-Experiences of a high-volume center.

PURPOSE: Patients with local recurrence of esophageal cancer have a highly decreased overall survival. There is currently no standardized treatment algorithm for this group. This retrospective cohort study aimed to evaluate the survival of patients with local recurrence, despite receiving individualized treatment options. METHODS: 241 of 1791 patients were diagnosed with a local recurrence following Ivor-Lewis esophagectomy at the University Hospital of Cologne. 59 patients, who were diagnosed only with a local recurrence of adeno- or squamous cell carcinoma and received their individualized therapy regimes at our high-volume center, were included. RESULTS: The study included 52 patients with adenocarcinoma and 7 with squamous cell carcinoma. Among these, 6 patients underwent resection, 19 received solely chemotherapy, 29 received chemoradiotherapy, and 5 were provided with best supportive care. Patients who underwent resection showed a better survival outcome compared to patients without resection (median OS: not reached vs. 15.1 months, p = 0.012). Best supportive care and palliative care were found to be independent risk factors for shorter overall survival compared to curative intended treatment options like local resection or chemoradiotherapy. CONCLUSION: In this study, different treatment strategies for patients with local recurrence of esophageal cancer were depicted. Resection as well as chemoradiotherapy could play a role in selected patients. Further prospective studies are needed to improve the selection of eligible patients.

Increased Risk of Incident Chronic Obstructive Pulmonary Disease and Related Hospitalizations in Tuberculosis Survivors: A Population-Based Matched Cohort Study.

BACKGROUND: Tuberculosis (TB) survivors have an increased risk of developing chronic obstructive pulmonary disease (COPD). This study assessed the risk of COPD development and COPD-related hospitalization in TB survivors compared to controls. METHODS: We conducted a population-based cohort study of TB survivors and 1:1 age- and sex-matched controls using data from the Korean National Health Insurance Service database collected from 2010 to 2017. We compared the risk of COPD development and COPD-related hospitalization between TB survivors and controls. RESULTS: Of the subjects, 9.6% developed COPD, and 2.8% experienced COPD-related hospitalization. TB survivors had significantly higher COPD incidence rates (36.7/1,000 vs. 18.8/1,000 person-years, P < 0.001) and COPD-related hospitalization (10.7/1,000 vs. 4.3/1,000 person-years, P < 0.001) than controls. Multivariable Cox regression analyses revealed higher risks of COPD development (adjusted hazard ratio [aHR], 1.63; 95% confidence interval [CI], 1.54-1.73) and COPD-related hospitalization (aHR, 2.03; 95% CI, 1.81-2.27) in TB survivors. Among those who developed COPD, the hospitalization rate was higher in individuals with post-TB COPD compared to those with non-TB COPD (10.7/1,000 vs. 4.9/1,000 person-years, P < 0.001), showing an increased risk of COPD-related hospitalization (aHR, 1.84; 95% CI, 1.17-2.92). CONCLUSION: TB survivors had higher risks of incident COPD and COPD-related hospitalization compared to controls. These results suggest that previous TB is an important COPD etiology associated with COPD-related hospitalization.

The Barriers to Recognizing and Reporting Child Physical Abuse by Emergency Physicians and Associated Factors.

BACKGROUND: Although the reporting rate of child abuse is increasing every year, the child abuse detection rate is 3.81% as of 2019 in Korea, which is significantly lower than that of developed countries for child rights. OBJECTIVE: We investigated the associated factors with barriers that emergency physicians face in recognizing and reporting cases of child abuse. METHODS: From May to July 2022, 240 emergency physicians working in the 15 emergency department were asked to participate in the survey via email. The questionnaire included the respondent's basic information, treatment experience for child abuse, reasons for reporting or not reporting, and opinions on measures to increase the reporting rate. We conducted a logistic regression analysis to discern the factors contributing to underreporting. RESULTS: Seventy-one individuals were included in the analysis, after excluding those who had never encountered suspected cases of child abuse. A multivariable logistic regression was performed with the above variables, and although it was not statistically significant, there was a tendency for workers to report well when working at a pediatric emergency department (odds ratio [95% confidence interval], 3.97 [0.98-16.09]). The primary reason for reporting suspected abuse was the pattern of damage suspected of abuse. The first reason for not reporting suspected abuse was because they were not sure it was child abuse. Respondents answered that to report better, a quick and appropriate response from the police and confidentiality of the reporter were needed. CONCLUSIONS: Physicians in pediatric emergency departments demonstrated a tendency for more proactive reporting suspected cases of child abuse.