Background: Worldwide, sepsis is the leading cause of death in hospitals. If mortality rates in patients with sepsis can be predicted early, medical resources can be allocated efficiently. We constructed machine learning (ML) models to predict the mortality of patients with sepsis in a hospital emergency department. Methods: This study prospectively collected nationwide data from an ongoing multicenter cohort of patients with sepsis identified in the emergency department. Patients were enrolled from 19 hospitals between September 2019 and December 2020. For acquired data from 3,657 survivors and 1,455 deaths, six ML models (logistic regression, support vector machine, random forest, extreme gradient boosting [XGBoost], light gradient boosting machine, and categorical boosting [CatBoost]) were constructed using fivefold cross-validation to predict mortality. Through these models, 44 clinical variables measured on the day of admission were compared with six sequential organ failure assessment (SOFA) components (PaO 2 /FIO 2 [PF], platelets (PLT), bilirubin, cardiovascular, Glasgow Coma Scale score, and creatinine).The confidence interval (CI) was obtained by performing 10,000 repeated measurements via random sampling of the test dataset. All results were explained and interpreted using Shapley’s additive explanations (SHAP). Results: Of the 5,112 participants, CatBoost exhibited the highest area under the curve (AUC) of 0.800 (95% CI, 0.756–0.840) using clinical variables. Using the SOFA components for the same patient, XGBoost exhibited the highest AUC of 0.678 (95% CI, 0.626–0.730). As interpreted by SHAP, albumin, lactate, blood urea nitrogen, and international normalization ratio were determined to significantly affect the results. Additionally, PF and PLTs in the SOFA component significantly influenced the prediction results. Conclusion Newly established ML-based models achieved good prediction of mortality in patients with sepsis. Using several clinical variables acquired at the baseline can provide more accurate results for early predictions than using SOFA components. Additionally, the impact of each variable was identified.

Purpose: Although osimertinib is the standard-of-care treatment of epidermal growth factor receptor (EGFR) T790M mutation–positive non–small cell lung cancer, real-world evidence on the efficacy of osimertinib is not enough to reflect the complexity of the entire course of treatment. Herein, we report on the use of osimertinib in patients with EGFR T790M mutation–positive non–small cell lung cancer who had previously received EGFR tyrosine kinase inhibitor (TKI) treatment in Korea. Materials and Methods: Patients with confirmed EGFR T790M after disease progression of prior EGFR-TKI were enrolled and administered osimertinib 80 mg daily. The primary effectiveness outcome was progression-free survival, with time-to-treatment discontinuation, treatment and adverse effects leading to treatment discontinuation, and overall survival being the secondary endpoints. Results: A total of 558 individuals were enrolled, and 55.2% had investigator-assessed responses. The median progression-free survival was 14.2 months (95% confidence interval [CI], 13.0 to 16.4), and the median time-to-treatment discontinuation was 15.0 months (95% CI, 14.1 to 15.9). The median overall survival was 36.7 months (95% CI, 30.9 to not reached). The benefit with osimertinib was consistent regardless of the age, sex, smoking history, and primary EGFR mutation subtype. However, hepatic metastases at the time of diagnosis, the presence of plasma EGFR T790M, and the shorter duration of prior EGFR-TKI treatment were poor predictors of osimertinib treatment. Ten patients (1.8%), including three with pneumonitis, had to discontinue osimertinib due to severe adverse effects. Conclusion Osimertinib demonstrated its clinical effectiveness and survival benefit for EGFR T790M mutation–positive in Korean patients with no new safety signals.

OBJECTIVES: We examined the associations of socioeconomic factors, health behaviors, and comorbidities with early-onset lung cancer. METHODS: The study included 6,794,287 individuals aged 20-39 years who participated in a Korean national health check-up program from 2009 to 2012. During the follow-up period, 4,684 participants developed lung cancer. Multivariable Cox regression analysis was used to estimate the independent associations of potential risk factors with incident lung cancer. RESULTS: Older age (multivariable hazard ratio [mHR], 1.13; 95% confidence interval [CI], 1.12 to 1.14) and female sex (mHR, 1.62; 95% CI, 1.49 to 1.75) were associated with increased lung cancer risk. Current smoking was also associated with elevated risk (<10 pack-years: mHR, 1.12; 95% CI, 1.01 to 1.24; ≥10 pack-years: mHR, 1.30; 95% CI, 1.18 to 1.45), but past smoking was not. Although mild alcohol consumption (<10 g/day) was associated with lower lung cancer risk (mHR, 0.92; 95% CI, 0.86 to 0.99), heavier alcohol consumption (≥10 g/day) was not. Higher income (highest vs. lowest quartile: mHR, 0.86; 95% CI, 0.78 to 0.94), physical activity for at least 1,500 metabolic equivalent of task-min/wk (vs. non-exercisers: mHR, 0.83; 95% CI, 0.69 to 0.99) and obesity (vs. normal weight: mHR, 0.89; 95% CI, 0.83 to 0.96) were associated with lower lung cancer risk, whereas metabolic syndrome was associated with increased risk (mHR, 1.13; 95% CI, 1.03 to 1.24). CONCLUSIONS In young adults, age, female sex, smoking, and metabolic syndrome were risk factors for early-onset lung cancer, while high income, physical activity, and obesity displayed protective effects.

Background: Gestational diabetes mellitus (GDM) is the most common metabolic complication of pregnancy. To define the altered pathway in GDM placenta, we investigated the transcriptomic profiles from human placenta between GDM and controls. Methods: Clinical parameters and postpartum complications were reviewed in all participants.Differentially expressed canonical pathways were analyzed between the GDM and control groups based on transcriptomic analysis. CD4 + T, CD8 + T, and senescent T cell subsets were determined by flow cytometry based on staining for specific intracellular cytokines. Results: Gene ontology analysis revealed that the placenta of GDM revealed upregulation of diverse mitochondria or DNA replication related pathways and downregulation of T-cell immunity related pathways. The maternal placenta of the GDM group had a higher proportion of CD4 + T and CD8 + T cells than the control group. Interestingly, senescent CD4 + T cells tended to increase and CD8 + T cells were significantly increased in GDM compared to controls, along with increased programmed cell death-1 (CD274 + ) expression. Programmed death-ligand 1 expression in syncytotrophoblasts was also significantly increased in patients with GDM. Conclusion This study demonstrated increased proinflammatory T cells, senescent T cells and immune-check point molecules in GDM placentas, suggesting that changes in senescent T cells and immune-escape signaling might be related to the pathophysiology of GDM.

Background: Decreased heart rate variability (HRV) has been reported to be associated with cardiac autonomic dysfunction. Hypopituitarism in nonfunctioning pituitary adenoma (NFPA) is often linked to increased cardiovascular mortality. We therefore hypothesized that postoperative NFPA patients with hormone deficiency have an elevated risk of HRV alterations indicating cardiac autonomic dysfunction. Methods: A total of 22 patients with NFPA were enrolled in the study. Between 3 and 6 months after surgery, a combined pituitary function test (CPFT) was performed, and HRV was measured. The period of sleep before the CPFT was deemed the most stable period, and the hypoglycemic period that occurred during the CPFT was defined as the most unstable period. Changes in HRV parameters in stable and unstable periods were observed and compared depending on the status of hormone deficiencies. Results: In patients with adrenocorticotropic hormone (ACTH) deficiency with other pituitary hormone deficiencies, the low frequency to high frequency ratio, which represents overall autonomic function and is increased in the disease state, was higher (P=0.005). Additionally, the standard deviation of the normal-to-normal interval, which decreases in the autonomic dysfunction state, was lower (P=0.030) during the hypoglycemic period. In panhypopituitarism, the low frequency to high frequency ratio during the hypoglycemic period was increased (P=0.007). Conclusion HRV analysis during CPFT enables estimation of cardiac autonomic dysfunction in patients with NFPA who develop ACTH deficiency with other pituitary hormone deficiencies or panhypopituitarism after surgery. These patients may require a preemptive assessment of cardiovascular risk.

Purpose: Various intervention strategies are needed to reduce the suicide rate among late adolescents. Therefore, we aimed to investigate the factors that can help overcome suicidal tendencies in late adolescents from the perspective of case managers. Methods: This qualitative study explored the reinforcing factors that can help overcome suicidal behaviors in late adolescents, by conducting focus group interviews with case managers from the local community. Interviews with 10 case managers were recorded and transcribed, and the data were analyzed using the content analysis method. Results: The main theme of this study was “a step in a new direction”. Three categories were derived: “inner changes”, “another possibility opened up by the interest of significant others”, and “connecting with community resources to help overcome”. Each category had subcategories that influenced the intention and course of action of behaviors to overcome the suicide crises. Conclusion Our findings, from the exploration of the experiences of case managers, provide an in-depth understanding of the reinforcing factors for overcoming suicide among late adolescents. They provide useful preliminary data for the development of effective suicide prevention programs for the adolescents.

Background: Decreased heart rate variability (HRV) has been reported to be associated with cardiac autonomic dysfunction. Hypopituitarism in nonfunctioning pituitary adenoma (NFPA) is often linked to increased cardiovascular mortality. We therefore hypothesized that postoperative NFPA patients with hormone deficiency have an elevated risk of HRV alterations indicating cardiac autonomic dysfunction. Methods: A total of 22 patients with NFPA were enrolled in the study. Between 3 and 6 months after surgery, a combined pituitary function test (CPFT) was performed, and HRV was measured. The period of sleep before the CPFT was deemed the most stable period, and the hypoglycemic period that occurred during the CPFT was defined as the most unstable period. Changes in HRV parameters in stable and unstable periods were observed and compared depending on the status of hormone deficiencies. Results: In patients with adrenocorticotropic hormone (ACTH) deficiency with other pituitary hormone deficiencies, the low frequency to high frequency ratio, which represents overall autonomic function and is increased in the disease state, was higher (P=0.005). Additionally, the standard deviation of the normal-to-normal interval, which decreases in the autonomic dysfunction state, was lower (P=0.030) during the hypoglycemic period. In panhypopituitarism, the low frequency to high frequency ratio during the hypoglycemic period was increased (P=0.007). Conclusion HRV analysis during CPFT enables estimation of cardiac autonomic dysfunction in patients with NFPA who develop ACTH deficiency with other pituitary hormone deficiencies or panhypopituitarism after surgery. These patients may require a preemptive assessment of cardiovascular risk.

Objective: This study compared the prognostic performance of the following five injury severity scores: the Geriatric Trauma Outcome Score (GTOS), the Injury Severity Score (ISS), the New Injury Severity Score (NISS), the Revised Trauma Score (RTS), and the Trauma and Injury Severity Score (TRISS) for in-hospital mortality in severe geriatric trauma patients. Methods: A retrospective, cross-sectional, observational study was conducted using a database of severe geriatric trauma patients (age ≥65 years and ISS ≥16) who presented to a single regional trauma center between November 2016 and October 2018. We compared the baseline characteristics between the survivor and mortality groups and the predictive ability of the five scoring systems. Results: A total of 402 patients were included in the analysis; the in-hospital mortality rate was 25.6% (n=103). The TRISS had the highest area under the curve of 0.953 (95% confidence interval [CI], 0.927-0.971); followed by RTS, 0.777 (95% CI, 0.733-0.817); NISS, 0.733 (95% CI, 0.687-0.776); ISS, 0.660 (95% CI, 0.612-0.707); and GTOS, 0.660 (95% CI, 0.611-0.706) in severe geriatric trauma. The TRISS also had the highest area under the curve of 0.961 (0.919-0.985) among the injury severity scoring systems in polytrauma. The predictive ability of TRISS was significantly higher than the other four scores with respect to overall trauma and polytrauma (P<0.001). Conclusion The TRISS showed the highest prognostic performance for predicting in-hospital mortality among all the injury severity scoring systems in severe geriatric trauma.

Purpose: To evaluate the clinical usefulness of a low vision aid using a virtual reality device (LVA-VR) in patients with low vision. Methods: Forty low vision patients were enrolled in this prospective study. All subjects participated in a two-session LVA-VR training course. The binocular best-corrected distance, intermediate, and near visual acuities (BCDVA, BCIVA, and BCNVA, respectively) were measured, along with contrast sensitivity and reading performance, at baseline and after 2 weeks of LVA-VR use. All subjects also provided a self-rated functional score (SFS) and completed a satisfaction questionnaire following the study. Results: Thirty-nine subjects (mean age, 54.6 ± 22.7 years) completed the study. Significant improvements in BCDVA, BCIVA, BCNVA, and contrast sensitivity were observed after 2 weeks of LVA-VR use (p < 0.001). Reading accuracy also improved significantly (p = 0.027); however, the reading speed did not change. Subject functionality improved, as indicated by the increase in the SFS (11.8 ± 4.5 vs. 19.6 ± 5.3) (p < 0.001). Most patients were satisfied with their visual function improvement and found LVA-VR to be useful in their daily activities. No device-related adverse events were observed or indicated. Conclusions This study suggests that LVA-VR is beneficial for visual rehabilitation. Future technological advances are expected to improve LVA-VR performance and acceptability further for a better quality of life in low vision patients.

Purpose: To report the successful rehabilitation of a patient with anomalous head posture by using a virtual reality low vision aid (VRLVA).Case summary: A 75-year-old male diagnosed with age-related macular degeneration 15 years prior presented with an anomalous head posture for eccentric viewing. He had central scotoma within the central 10 degrees, and the preferred retinal locus (PRL) was localized to the inferonasal retina. The patient underwent a training session on the use of the VRLVA, which has a remapping function to remap distorted images, and those falling on the scotoma, to another location on the screen. After explaining the purpose of the VRLVA, the patient was given the device to use at home for two weeks. At two weeks after training, the patient could look straight ahead when using the VRLVA, without anomalous head posture. In addition, reading performance, including speed and accuracy, improved; moreover, he experienced no device-related adverse events. Conclusions By using the VRLVA, low-vision patients with anomalous head posture can shift images falling on the central scotoma to the PRL, thereby minimizing their anomalous head posture and improving reading performance. We expect that future technological advances, such as a wearable design and the use of lightweight material, will further improve the performance and acceptability of the VRLVA.