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Background Endothelial activation and stress index (EASIX) reflects endothelial dysfunction or damage. Because endothelial dysfunction is one of the key mechanisms, a few studies have shown the clinical usefulness of original and age-adjusted EASIX (age-EASIX) in patients with coronavirus disease 2019 (COVID-19). We aimed to evaluate the clinical utility of age-EASIX in predicting intensive care unit (ICU) mortality in critically ill patients with COVID-19 in South Korea. Methods Secondary analysis was performed using clinical data retrospectively collected from 22 nationwide hospitals in South Korea between January 1, 2020, and August 31, 2021. Patients were at least 19 years old and admitted to the ICU for severe COVID-19, demanding at least high-flow nasal cannula oxygen therapy. EASIX [lactate dehydrogenase (U/L)×creatinine (mg/dL)/platelet count (109 cells/L)] and age-EASIX (EASIX×age) were calculated and log2-transformed. Results The mean age of 908 critically ill patients with COVID-19 was 67.4 years with 59.7% male sex. The mean log2 age-EASIX was 7.38±1.45. Non-survivors (n=222, 24.4%) in the ICU had a significantly higher log2 age-EASIX than of survivors (8.2±1.52 vs. 7.1±1.32, p

Noise reduction in low-dose positron emission tomography (PET) is a well-researched topic aimed at reducing patient radiation doses and improving diagnosis. Software-based noise reduction mainly improves the contrast between regions by reducing the variation of the acquired image. However, it should be performed under appropriate parameters to reduce discrimination. We propose a method that derives optimal noise-reduction parameters using the multi-scale structural similarity index measure and visual information fidelity, which are metrics for image quality assessment. Simulation and experimental studies demonstrated the viability of the proposed algorithm. The contrast-to-noise ratio value of the denoised reconstruction slice, which was used as the optimal parameter, increased approximately three times compared to that of the low-dose slice while preserving the resolution. The results indicate that the proposed method successfully predicted the parameters according to the noise-reduction algorithm and PET system conditions in the sinogram domain. The proposed algorithm should help prevent misdiagnosis and provide standardized medical images for clinical application by performing appropriate noise reduction.

Background/Aims Intensive care unit (ICU) quality is largely determined by the mortality rate. Therefore, we aimed to develop and validate a novel prognostic model for predicting mortality in Korean ICUs, using national insurance claims data. Methods Data were obtained from the health insurance claims database maintained by the Health Insurance Review and Assessment Service of South Korea. From patients who underwent the third ICU adequacy evaluation, 42,489 cases were enrolled and randomly divided into the derivation and validation cohorts. Using the models derived from the derivation cohort, we analyzed whether they accurately predicted death in the validation cohort. The models were verified using data from one general and two tertiary hospitals. Results Two severity correction models were created from the derivation cohort data, by applying variables selected through statistical analysis, through clinical consensus, and from performing multiple logistic regression analysis. Model 1 included six categorical variables (age, sex, Charlson comorbidity index, ventilator use, hemodialysis or continuous renal replacement therapy, and vasopressor use). Model 2 additionally included presence/absence of ICU specialists and nursing grades. In external validation, the performance of models 1 and 2 for predicting in-hospital and ICU mortality was not inferior to that of pre-existing scoring systems. Conclusions The novel and simple models could predict in-hospital and ICU mortality and were not inferior compared to the pre-existing scoring systems.

Abstract N 6-adenosine methylation (m6A) is critical for controlling cancer cell growth and tumorigenesis. However, the function and detailed mechanism of how m6A methyltransferases modulate m6A levels on specific targets remain unknown. In the current study, we identified significantly elevated levels of RBM15, an m6A writer, in basal-like breast cancer (BC) patients compared to nonbasal-like BC patients and linked this increase to worse clinical outcomes. Gene expression profiling revealed correlations between RBM15 and serine and glycine metabolic genes, including PHGDH, PSAT1, PSPH, and SHMT2. RBM15 influences m6A levels and, specifically, the m6A levels of serine and glycine metabolic genes via direct binding to target RNA. The effects of RBM15 on cell growth were largely dependent on serine and glycine metabolism. Thus, RBM15 coordinates cancer cell growth through altered serine and glycine metabolism, suggesting that RBM15 is a new therapeutic target in BC.

Esophageal perforation can lead to serious complications, and rapid diagnosis and treatment significantly affect the prognosis. Endoscopic vacuum-assisted closure (EndoVAC) therapy is widely accepted as a safe, well-tolerated, effective, versatile and practical procedure for the management of esophageal perforation in selected patients. We report the successful use of EndoVAC therapy for management of an esophageal perforation secondary to foreign body removal. A 56-year-old man presented to the emergency department for evaluation of chest pain after swallowing the plastic shell of a pill. Emergency endoscopy revealed an esophageal wall laceration (approximately 3 cm) and microperforation. The esophageal laceration and microperforation were limited to the mid-esophagus. The patient underwent EndoVAC therapy, which was repeated every 3–4 days for a total of six sessions over a period of 21 days. We observed improvement in the esophageal injury with granulation tissue formation during the fifth session. Subsequent follow-up evaluation, including esophagography and chest computed tomography confirmed complete healing of the esophageal injury. Following resumption of diet, the patienton a was discharged without any complications.

Refrigerators account for 20–30 % of household electricity consumption, with the compressor contributing to 80 % of the total consumption. Therefore, it is essential to increase the compressor efficiency. One approach to enhance compressor performance involves increasing heat dissipation to lower the temperature of the suction system and boost the refrigerant density entering the suction chamber. To achieve that innovatively, we harnessed the waste vibration of the linear compressor body to create a gap flow between the body and the housing, enhancing compressor performance by augmenting heat dissipation. Measurements of gap flow temperature, cylinder surface temperature, and heat flux on the cylinder surface were conducted, varying the RPM, gap size, and the shape of the gap flow path. We also observed variations in the gap flow rate with RPM and stroke. The results revealed that gap temperature and heat flux increased with higher RPM and smaller gap size, and the application of ribs to the gap flow path proved to be more effective in enhancing temperature and heat flux. Additionally, it is anticipated that heat flux will further increase with a longer stroke as the flow rate increases. Therefore, to optimize heat dissipation through gap flow using the waste vibration of the compressor body, it is advantageous to employ a smaller gap size, higher RPM, longer stroke, and apply ribs to the gap flow path. Future research should focus on verifying the effectiveness of increased heat dissipation and improved Energy Efficiency Ratio (EER) through actual compressor experiments.

OBJECTIVES:. Anemia has been associated with an increased risk of both cardiac arrest and stroke, frequent complications of COVID-19. The effect of hemoglobin level at ICU admission on a composite outcome of cardiac arrest or stroke in an international cohort of COVID-19 patients was investigated. DESIGN:. Retrospective analysis of prospectively collected database. SETTING:. A registry of COVID-19 patients admitted to ICUs at over 370 international sites was reviewed for patients diagnosed with cardiac arrest or stroke up to 30 days after ICU admission. Anemia was defined as: normal (hemoglobin ≥ 12.0 g/dL for women, ≥ 13.5 g/dL for men), mild (hemoglobin 10.0–11.9 g/dL for women, 10.0–13.4 g/dL for men), moderate (hemoglobin ≥ 8.0 and < 10.0 g/dL for women and men), and severe (hemoglobin < 8.0 g/dL for women and men). PATIENTS:. Patients older than 18 years with acute COVID-19 infection in the ICU. INTERVENTIONS:. None. MEASUREMENTS AND MAIN RESULTS:. Of 6926 patients (median age = 59 yr, male = 65%), 760 patients (11.0%) experienced stroke (2.0%) and/or cardiac arrest (9.4%). Cardiac arrest or stroke was more common in patients with low hemoglobin, occurring in 12.8% of patients with normal hemoglobin, 13.3% of patients with mild anemia, and 16.7% of patients with moderate/severe anemia. Time to stroke or cardiac arrest by anemia status was analyzed using Cox proportional hazards regression with death as a competing risk. Covariates selected through clinical knowledge were age, sex, comorbidities (diabetes, hypertension, obesity, and cardiac or neurologic conditions), pandemic era, country income, mechanical ventilation, and extracorporeal membrane oxygenation. Moderate/severe anemia was associated with a higher risk of cardiac arrest or stroke (hazard ratio, 1.32; 95% CI, 1.05–1.67). CONCLUSIONS:. In an international registry of ICU patients with COVID-19, moderate/severe anemia was associated with increased hazard of cardiac arrest or stroke.

Background: While extensive studies have elucidated the relationships between exposure to air pollution and chronic diseases, such as cardiovascular disorders and diabetes, the intricate effects on specific kidney diseases, notably primary glomerulonephritis (GN)—an immune-mediated kidney ailment—are less well understood. Considering the escalating incidence of GN and conspicuous lack of investigative focus on its association with air quality, investigation is dedicated to examining the long-term effects of air pollutants on renal function in individuals diagnosed with primary GN. Methods: This retrospective cohort analysis was conducted on 1394 primary GN patients who were diagnosed at Seoul National University Bundang Hospital and Seoul National University Hospital. Utilizing time-varying Cox regression and linear mixed models (LMM), we examined the effect of yearly average air pollution levels on renal function deterioration (RFD) and change in estimated glomerular filtration rate (eGFR). In this context, RFD is defined as sustained eGFR of less than 60 mL/min per 1.73 m2. Results: During a mean observation period of 5.1 years, 350 participants developed RFD. Significantly, elevated interquartile range (IQR) levels of air pollutants—including PM10 (particles ≤10 micrometers, HR 1.389, 95 % CI 1.2–1.606), PM2.5 (particles ≤2.5 micrometers, HR 1.353, 95 % CI 1.162–1.575), CO (carbon monoxide, HR 1.264, 95 % CI 1.102–1.451), and NO2 (nitrogen dioxide, HR 1.179, 95 % CI 1.021–1.361)—were significantly associated with an increased risk of RFD, after factoring in demographic and health variables. Moreover, exposure to PM10 and PM2.5 was associated with decreased eGFR. Conclusions: This study demonstrates a substantial link between air pollution exposure and renal function impairment in primary GN, accentuating the significance of environmental determinants in the pathology of immune-mediated kidney diseases.

Abstract Background Given the rising awareness of health-related lifestyle modifications, the impact of changes in body weight (BW) on cognitive function and dementia generates significant concern. This study aimed to investigate the association between BW changes and dementia in a middle-aged Korean population. Methods A retrospective, population-based longitudinal study was conducted utilizing data from the National Health Insurance Service (NHIS) database. Participants aged 40 years or older in 2011 who underwent at least five health checkups between 2002 and 2011 were followed-up for dementia until 2020. A total of 3,635,988 dementia-free Korean aged

Background Results of studies investigating the association between body mass index (BMI) and mortality in patients with coronavirus disease-2019 (COVID-19) have been conflicting. Methods This multicenter, retrospective observational study, conducted between January 2020 and August 2021, evaluated the impact of obesity on outcomes in patients with severe COVID-19 in a Korean national cohort. A total of 1,114 patients were enrolled from 22 tertiary referral hospitals or university-affiliated hospitals, of whom 1,099 were included in the analysis, excluding 15 with unavailable height and weight information. The effect(s) of BMI on patients with severe COVID-19 were analyzed. Results According to the World Health Organization BMI classification, 59 patients were underweight, 541 were normal, 389 were overweight, and 110 were obese. The overall 28-day mortality rate was 15.3%, and there was no significant difference according to BMI. Univariate Cox analysis revealed that BMI was associated with 28-day mortality (hazard ratio, 0.96; p=0.045), but not in the multivariate analysis. Additionally, patients were divided into two groups based on BMI ≥25 kg/m2 and underwent propensity score matching analysis, in which the two groups exhibited no significant difference in mortality at 28 days. The median (interquartile range) clinical frailty scale score at discharge was higher in nonobese patients (3 [3 to 5] vs. 4 [3 to 6], p

Abstract This study aims to propose a generative deep learning model (GDLM) based on a variational autoencoder that predicts macular optical coherence tomography (OCT) images following full-thickness macular hole (FTMH) surgery and evaluate its clinical accuracy. Preoperative and 6-month postoperative swept-source OCT data were collected from 150 patients with successfully closed FTMH using 6 × 6 mm2 macular volume scan datasets. Randomly selected and augmented 120,000 training and 5000 validation pairs of OCT images were used to train the GDLM. We assessed the accuracy and F1 score of concordance for neurosensory retinal areas, performed Bland–Altman analysis of foveolar height (FH) and mean foveal thickness (MFT), and predicted postoperative external limiting membrane (ELM) and ellipsoid zone (EZ) restoration accuracy between artificial intelligence (AI)-OCT and ground truth (GT)-OCT images. Accuracy and F1 scores were 94.7% and 0.891, respectively. Average FH (228.2 vs. 233.4 μm, P = 0.587) and MFT (271.4 vs. 273.3 μm, P = 0.819) were similar between AI- and GT-OCT images, within 30.0% differences of 95% limits of agreement. ELM and EZ recovery prediction accuracy was 88.0% and 92.0%, respectively. The proposed GDLM accurately predicted macular OCT images following FTMH surgery, aiding patient and surgeon understanding of postoperative macular features.

Abstract Background Whether COVID-19-induced acute respiratory distress syndrome (ARDS) should be approached differently in terms of mechanical ventilation therapy compared to other virus-induced ARDS is debatable. Therefore, we aimed to ascertain whether the respiratory mechanical characteristics of COVID-19-induced ARDS differ from those of influenza A induced ARDS, in order to establish a rationale for mechanical ventilation therapy in COVID-19-induced ARDS. Methods This was a retrospective cohort study comparing patients with COVID-19-induced ARDS and influenza A induced ARDS. We included intensive care unit (ICU) patients with COVID-19 or Influenza A aged ≥ 19, who were diagnosed with ARDS according to the Berlin definition between January 2015 and July 2021. Ventilation parameters for respiratory mechanics were collected at specific times on days one, three, and seven after intubation. Results The median age of the 87 participants was 71.0 (62.0–78.0) years old, and 63.2% were male. The ratio of partial pressure of oxygen in arterial blood to the fractional of inspiratory oxygen concentration in COVID-19-induced ARDS was lower than that in influenza A induced ARDS during the initial stages of mechanical ventilation (influenza A induced ARDS 216.1 vs. COVID-19-induced ARDS 167.9, p = 0.009, day 1). The positive end expiratory pressure remained consistently higher in the COVID-19 group throughout the follow-up period (7.0 vs. 10.0, p

Background Individuals increasingly turn to the Internet for health information, with YouTube being a prominent source. However, the quality and reliability of the health information vary widely, potentially affecting health literacy and behavioural intentions. Methods To analyse the impact of health information quality on health literacy and behavioural intention, we conducted a randomized controlled trial using a quality-controlled YouTube intervention. Health information quality on YouTube was evaluated using the Global Quality Score and DISCERN. We randomly allocated (1 : 1) to the intervention group to watch the highest quality-evaluated content and to the control group to watch the lowest quality-evaluated content. Health literacy and health behavioural intention were assessed before and after watching YouTube. The trial was set for two different topics: interpreting laboratory test results from health check-up and information about inflammatory bowel disease (IBD). Results From 8 April 2022 to 15 April 2022, 505 participants were randomly assigned to watch either high-quality content (intervention group, n = 255) or low-quality content (control group, n = 250). Health literacy significantly improved in the intervention group (28.1 before and 31.8 after; p

Background: COVID-19 is primarily known as a respiratory illness; however, many patients present to hospital without respiratory symptoms. The association between non-respiratory presentations of COVID-19 and outcomes remains unclear. We investigated risk factors and clinical outcomes in patients with no respiratory symptoms (NRS) and respiratory symptoms (RS) at hospital admission. Methods: This study describes clinical features, physiological parameters, and outcomes of hospitalised COVID-19 patients, stratified by the presence or absence of respiratory symptoms at hospital admission. RS patients had one or more of: cough, shortness of breath, sore throat, runny nose or wheezing; while NRS patients did not. Results: Of 178,640 patients in the study, 86.4 % presented with RS, while 13.6 % had NRS. NRS patients were older (median age: NRS: 74 vs RS: 65) and less likely to be admitted to the ICU (NRS: 36.7 % vs RS: 37.5 %). NRS patients had a higher crude in-hospital case-fatality ratio (NRS 41.1 % vs. RS 32.0 %), but a lower risk of death after adjusting for confounders (HR 0.88 [0.83–0.93]). Conclusion: Approximately one in seven COVID-19 patients presented at hospital admission without respiratory symptoms. These patients were older, had lower ICU admission rates, and had a lower risk of in-hospital mortality after adjusting for confounders.

Background Surgical techniques for small kidney tumors have been developed for decades, from open to robotic surgery. There are two approaches for partial nephrectomy: transperitoneal and retroperitoneal. We divided robotic partial nephrectomy cases into transperitoneal robotic partial nephrectomy (TRPN) and retroperitoneal robotic partial nephrectomy (RRPN) and compared the outcomes. Methods We retrospectively evaluated patients who underwent robotic partial nephrectomy at our hospital between November 2019 and May 2022. We reviewed patients’ demographic and perioperative data. Results Seventy robotic partial nephrectomies were performed (35 TRPN and 35 RRPN). There were significant differences in operation time, estimated blood loss (EBL), tumor size, and the RENAL Nephrometry Score (RNS) between those who underwent TRPN and those who underwent RRPN. Larger tumors were noted in the TRPN group, and the RNS was higher. In contrast, the operation time was shorter, EBL was lower, and tumors were more likely to be located in the posterior and lower portions in the RRPN group than in the TRPN group. Conclusions In our study, RRPN had advantages over TRPN in terms of operation time and EBL. However, TRPN tended to be performed rather than RRPN for tumors that were more complex in terms of size or RNS. Although the choice between RRPN and TRPN depends on the surgeon's preference, RRPN seems effective for treating small kidney tumors if selected appropriately.

Background Retzius-sparing robot-assisted radical prostatectomy (rsRARP) is a surgical procedure that can minimize the resection of surrounding prostate tissue by enabling access through the anterior surface of the Douglas pouch. We reported our initial experiences with rsRARP compared to conventional robot-assisted radical prostatectomy (RARP). Methods Retrospective data were collected from March 2019 to June 2022, including 69 patients who underwent robotic radical prostatectomy for localized prostate cancer. The operations were performed at a single center, and we alternated between the two methods. Perioperative characteristics and oncologic and functional outcomes were analyzed. Results In total, 35 patients underwent RARP and 34 patients underwent rsRARP. The preoperative characteristics of the patients were similar. Oncologic and functional parameters were analyzed postoperatively. Except for early recovery of urinary incontinence (immediate, 1 month, 3 months, 6 months: p

Abstract Background In the global trend of population aging, age is one of the significant factors to be considered in critically ill patients. However, the impact of age on clinical outcomes and long-term prognosis in this population varies across different studies. Methods We conducted a retrospective cohort analysis for patients admitted to the medical intensive care unit (ICU) (30 beds) between January 2017 and December 2020 at the tertiary referral hospital in Korea. Patients were classified into three groups according to age:

Abstract Background Cancer cells undergo cellular adaptation through metabolic reprogramming to sustain survival and rapid growth under various stress conditions. However, how brain tumors modulate their metabolic flexibility in the naturally serine/glycine (S/G)-deficient brain microenvironment remain unknown. Methods We used a range of primary/stem-like and established glioblastoma (GBM) cell models in vitro and in vivo. To identify the regulatory mechanisms of S/G deprivation-induced metabolic flexibility, we employed high-throughput RNA-sequencing, transcriptomic analysis, metabolic flux analysis, metabolites analysis, chromatin immunoprecipitation (ChIP), luciferase reporter, nuclear fractionation, cycloheximide-chase, and glucose consumption. The clinical significances were analyzed in the genomic database (GSE4290) and in human GBM specimens. Results The high-throughput RNA-sequencing and transcriptomic analysis demonstrate that the de novo serine synthesis pathway (SSP) and glycolysis are highly activated in GBM cells under S/G deprivation conditions. Mechanistically, S/G deprivation rapidly induces reactive oxygen species (ROS)-mediated AMP-activated protein kinase (AMPK) activation and AMPK-dependent hypoxia-inducible factor (HIF)-1α stabilization and transactivation. Activated HIF-1α in turn promotes the expression of SSP enzymes phosphoglycerate dehydrogenase (PHGDH), phosphoserine aminotransferase 1 (PSAT1), and phosphoserine phosphatase (PSPH). In addition, the HIF-1α-induced expression of glycolytic genes (GLUT1, GLUT3, HK2, and PFKFB2) promotes glucose uptake, glycolysis, and glycolytic flux to fuel SSP, leading to elevated de novo serine and glycine biosynthesis, NADPH/NADP+ ratio, and the proliferation and survival of GBM cells. Analyses of human GBM specimens reveal that the levels of overexpressed PHGDH, PSAT1, and PSPH are positively correlated with levels of AMPK T172 phosphorylation and HIF-1α expression and the poor prognosis of GBM patients. Conclusion Our findings reveal that metabolic stress-enhanced glucose-derived de novo serine biosynthesis is a critical metabolic feature of GBM cells, and highlight the potential to target SSP for treating human GBM.

AbstractBackground Systemic sclerosis (SSc) is a heterogeneous autoimmune disease characterized by dysregulation of fibroblast function, which often involves the lungs. Interstitial lung disease (ILD) associated with SSc (SSc-ILD) is a major cause of death among patients with SSc. Our study aimed to identify risk factors for mortality and compare the clinical characteristics of patients with SSc-ILD.Patients and methods Patients were retrospectively enrolled between 2010 and 2018 in a tertiary hospital in Korea. Patients with SSc-ILD were classified depending on the first pulmonary function test or radiologic findings: extensive (n = 46, >20% disease extent on computed tomography (CT) or forced vital capacity [FVC]

The BiFeO3-BaTiO3 (BF-BT) ceramics were here prepared through the solid-state reaction of Bi2O3, Fe2O3 and nano-sized BT powders. The crystal structures and piezoelectric properties were investigated in both quenched (AQ) and slowly cooled (SC) 0.7BF-0.3BT ceramics. Prior work has shown that rhombohedral and pseudo-cubic phases coexist in 0.7BF-0.3BT ceramics. In this work, the crystal structure of the pseudo-cubic phase was refined as a non-polar orthorhombic Pbnm phase in the SC sample and as a polar orthorhombic Pmc21 phase in the AQ sample. In addition to a sharp dielectric peak at about 620 °C, corresponding to the Curie temperature of the rhombohedral phase, a broad dielectric peak with strong frequency dispersion and a sharp frequency-independent dielectric peak were observed at around 500 °C in the SC and AQ samples, respectively. We determine that the dielectric anomalies around 500 °C were caused by a relaxor phase transition of the non-polar orthorhombic phase in the SC sample and a ferroelectric–paraelectric phase transition of the polar orthorhombic phase in the AQ sample. The AQ sample showed better ferroelectric and piezoelectric properties than the SC sample. The 0.7BF-0.3BT ceramic slowly cooled in a nitrogen atmosphere showed a well-saturated P-E curve and a similar temperature-dependent dielectric constant as the AQ sample. Our results indicate that large concentrations of oxygen vacancies produce a more distorted polar orthorhombic phase and better piezoelectric properties in the AQ sample than in the SC sample.

A ventilator central monitoring system (VCMS) that can efficiently respond to and treat patients’ respiratory issues in intensive care units (ICUs) is critical. Using Internet of Things (IoT) technology without loss or delay in patient monitoring data, clinical staff can overcome spatial constraints in patient respiratory management by integrated monitoring of multiple ventilators and providing real-time information through remote mobile applications. This study aimed to establish a VCMS and assess its effectiveness in an ICU setting. A VCMS comprises central monitoring and mobile applications, with significant real-time information from multiple patient monitors and ventilator devices stored and managed through the VCMS server, establishing an integrated monitoring environment on a web-based platform. The developed VCMS was analyzed in terms of real-time display and data transmission. Twenty-one respiratory physicians and staff members participated in usability and satisfaction surveys on the developed VCMS. The data transfer capacity derived an error of approximately 10−7, and the difference in data transmission capacity was approximately 1.99×10−7±9.97×10−6 with a 95% confidence interval of −1.16×10−7 to 5.13×10−7 among 18 ventilators and patient monitors. The proposed VCMS could transmit data from various devices without loss of information within the ICU. The medical software validation, consisting of 37 tasks and 9 scenarios, showed a task completion rate of approximately 92%, with a 95% confidence interval of 88.81–90.43. The satisfaction survey consisted of 23 items and showed results of approximately 4.66 points out of 5. These results demonstrated that the VCMS can be readily used by clinical ICU staff, confirming its clinical utility and applicability. The proposed VCMS can help clinical staff quickly respond to the alarm of abnormal events and diagnose and treat based on longitudinal patient data. The mobile applications overcame space constraints, such as isolation to prevent respiratory infection transmission of clinical staff for continuous monitoring of respiratory patients and enabled rapid consultation, ensuring consistent care.

Objectives: Little is known about the disparities in underweight prevalence among the general population in high-income countries. We investigated the trends in underweight prevalence and disparities across sociodemographic groups among Korean adults and older adults. Setting and participants: A series of cross-sectional data on Korean national health checkups for adults aged ≥20 years were analyzed from 2005 to 2016. Measurements: Based on body mass index (kg/m2), underweight was graded as mild (17.0–18.49), moderate (16.0–16.9), and severe (

BackgroundDuring the height of the COVID-19 pandemic, the Korean government temporarily allowed full scale telehealth care for safety and usability. However, limited studies have evaluated the impact of telehealth by analyzing the physical and/or mental health data of patients with COVID-19 diagnosis collected through telehealth targeting Korean population.ObjectiveThis study aimed to identify subgroup of depressive symptom trajectories in patients with clinically mild COVID-19 using collected longitudinal data from a telehealth-based contactless clinical trial.MethodsA total of 199 patients with COVID-19 were accrued for contactless clinical trial using telehealth from March 23 to July 20, 2022. Depressive symptoms were measured using the patient health questionnaire-9 on the start day of quarantine, on the final day of quarantine, and 1 month after release from quarantine. Additionally, acute COVID-19 symptoms were assessed every day during quarantine. This study used a latent class mixed model to differentiate subgroups of depressive symptom trajectories and a logistic regression model with Firth’s correction to identify associations between acute COVID-19 symptoms and the subgroups.ResultsTwo latent classes were identified: class 1 with declining linearity at a slow rate and class 2 with increasing linearity. Among COVID-19 symptoms, fever, chest pain, and brain fog 1 month after release from quarantine showed strong associations with class 2 (fever: OR, 19.43, 95% CI, 2.30–165.42; chest pain: OR, 6.55, 95% CI, 1.15–34.61; brain fog: OR, 7.03, 95% CI 2.57–20.95). Sleeping difficulty and gastrointestinal symptoms were also associated with class 2 (gastrointestinal symptoms: OR, 4.76, 95% CI, 1.71–14.21; sleeping difficulty: OR, 3.12, 95% CI, 1.71–14.21).ConclusionThese findings emphasize the need for the early detection of depressive symptoms in patients in the acute phase of COVID-19 using telemedicine. Active intervention, including digital therapeutics, may help patients with aggravated depressive symptoms.

BackgroundFew studies have used standardized nursing records with Systematized Nomenclature of Medicine–Clinical Terms (SNOMED CT) to identify predictors of clinical deterioration. ObjectiveThis study aims to standardize the nursing documentation records of patients with COVID-19 using SNOMED CT and identify predictive factors of clinical deterioration in patients with COVID-19 via standardized nursing records. MethodsIn this study, 57,558 nursing statements from 226 patients with COVID-19 were analyzed. Among these, 45,852 statements were from 207 patients in the stable (control) group and 11,706 from 19 patients in the exacerbated (case) group who were transferred to the intensive care unit within 7 days. The data were collected between December 2019 and June 2022. These nursing statements were standardized using the SNOMED CT International Edition released on November 30, 2022. The 260 unique nursing statements that accounted for the top 90% of 57,558 statements were selected as the mapping source and mapped into SNOMED CT concepts based on their meaning by 2 experts with more than 5 years of SNOMED CT mapping experience. To identify the main features of nursing statements associated with the exacerbation of patient condition, random forest algorithms were used, and optimal hyperparameters were selected for nursing problems or outcomes and nursing procedure–related statements. Additionally, logistic regression analysis was conducted to identify features that determine clinical deterioration in patients with COVID-19. ResultsAll nursing statements were semantically mapped to SNOMED CT concepts for “clinical finding,” “situation with explicit context,” and “procedure” hierarchies. The interrater reliability of the mapping results was 87.7%. The most important features calculated by random forest were “oxygen saturation below reference range,” “dyspnea,” “tachypnea,” and “cough” in “clinical finding,” and “oxygen therapy,” “pulse oximetry monitoring,” “temperature taking,” “notification of physician,” and “education about isolation for infection control” in “procedure.” Among these, “dyspnea” and “inadequate food diet” in “clinical finding” increased clinical deterioration risk (dyspnea: odds ratio [OR] 5.99, 95% CI 2.25-20.29; inadequate food diet: OR 10.0, 95% CI 2.71-40.84), and “oxygen therapy” and “notification of physician” in “procedure” also increased the risk of clinical deterioration in patients with COVID-19 (oxygen therapy: OR 1.89, 95% CI 1.25-3.05; notification of physician: OR 1.72, 95% CI 1.02-2.97). ConclusionsThe study used SNOMED CT to express and standardize nursing statements. Further, it revealed the importance of standardized nursing records as predictive variables for clinical deterioration in patients.

BackgroundMeasurement of sodium intake in hospitalized patients is critical for their care. In this study, artificial intelligence (AI)–based imaging was performed to determine sodium intake in these patients. ObjectiveThe applicability of a diet management system was evaluated using AI-based imaging to assess the sodium content of diets prescribed for hospitalized patients. MethodsBased on the information on the already investigated nutrients and quantity of food, consumed sodium was analyzed through photographs obtained before and after a meal. We used a hybrid model that first leveraged the capabilities of the You Only Look Once, version 4 (YOLOv4) architecture for the detection of food and dish areas in images. Following this initial detection, 2 distinct approaches were adopted for further classification: a custom ResNet-101 model and a hyperspectral imaging-based technique. These methodologies focused on accurate classification and estimation of the food quantity and sodium amount, respectively. The 24-hour urine sodium (UNa) value was measured as a reference for evaluating the sodium intake. ResultsResults were analyzed using complete data from 25 participants out of the total 54 enrolled individuals. The median sodium intake calculated by the AI algorithm (AI-Na) was determined to be 2022.7 mg per day/person (adjusted by administered fluids). A significant correlation was observed between AI-Na and 24-hour UNa, while there was a notable disparity between them. A regression analysis, considering patient characteristics (eg, gender, age, renal function, the use of diuretics, and administered fluids) yielded a formula accounting for the interaction between AI-Na and 24-hour UNa. Consequently, it was concluded that AI-Na holds clinical significance in estimating salt intake for hospitalized patients using images without the need for 24-hour UNa measurements. The degree of correlation between AI-Na and 24-hour UNa was found to vary depending on the use of diuretics. ConclusionsThis study highlights the potential of AI-based imaging for determining sodium intake in hospitalized patients.

Summary: Background: Diabetes is a major public health concern. We aimed to evaluate the long-term risk of incident type 2 diabetes in a non-diabetic population using a deep learning model (DLM) detecting prevalent type 2 diabetes using electrocardiogram (ECG). Methods: In this retrospective study, participants who underwent health checkups at two tertiary hospitals in Seoul, South Korea, between Jan 1, 2001 and Dec 31, 2022 were included. Type 2 diabetes was defined as glucose ≥126 mg/dL or glycated haemoglobin (HbA1c) ≥ 6.5%. For survival analysis on incident type 2 diabetes, we introduced an additional variable, diabetic ECG, which is determined by the DLM trained on ECG and corresponding prevalent diabetes. It was assumed that non-diabetic individuals with diabetic ECG had a higher risk of incident type 2 diabetes than those with non-diabetic ECG. The one-dimensional ResNet-based model was adopted for the DLM, and the Guided Grad-CAM was used to localise important regions of ECG. We divided the non-diabetic group into the diabetic ECG group (false positive) and the non-diabetic ECG (true negative) group according to the DLM decision, and performed a Cox proportional hazard model, considering the occurrence of type 2 diabetes more than six months after the visit. Findings: 190,581 individuals were included in the study with a median follow-up period of 11.84 years. The areas under the receiver operating characteristic curve for prevalent type 2 diabetes detection were 0.816 (0.807–0.825) and 0.762 (0.754–0.770) for the internal and external validations, respectively. The model primarily focused on the QRS duration and, occasionally, P or T waves. The diabetic ECG group exhibited an increased risk of incident type 2 diabetes compared with the non-diabetic ECG group, with hazard ratios of 2.15 (1.82–2.53) and 1.92 (1.74–2.11) for internal and external validation, respectively. Interpretation: In the non-diabetic group, those whose ECG was classified as diabetes by the DLM were at a higher risk of incident type 2 diabetes than those whose ECG was not. Additional clinical research on the relationship between the phenotype of ECG and diabetes to support the results and further investigation with tracked data and various ECG recording systems are suggested for future works. Funding: National Research Foundation of Korea.

Abstract Purpose To evaluate the clinical patterns of retinopathy in patients who received cardiopulmonary resuscitation (CPR) using wide-field fundus photography and slit-lamp fundus examination. Methods The medical records of patients aged ≥ 18 years who survived after receiving CPR and underwent wide-field fundus photography and slit-lamp fundus examination within 3 months were retrospectively analyzed. Fundus findings, including retinal hemorrhage and cotton wool spots, were investigated. The subjects were categorized into the retinopathy and non-retinopathy groups based on the presence of fundus findings. Systemic and CPR-related factors were analyzed to compare the two groups. Results Twenty eyes (10 patients) and 28 eyes (14 patients) were included in the retinopathy and non-retinopathy groups, respectively. The retinopathy group had longer CPR time than the non-retinopathy group (15 ± 11 min vs. 6 ± 5 min, p = 0.027). In the retinopathy group, retinal nerve fiber layer hemorrhage was observed in all eyes, and intraretinal hemorrhage was observed in 55% of the eyes. 80% of hemorrhages were located in the peripapillary or posterior pole. There were no interval changes in visual acuity, intraocular pressure, and central retinal thickness for 6 months. The average remission periods of retinal hemorrhage and cotton wool spots were 6.8 ± 2.6 month and 5.6 ± 2.1 months, respectively. No retinopathy progression was observed. Conclusion The signs of retinopathy, such as retinal hemorrhages and cotton wool spots, which are found after CPR, mainly occur in patients who receive longer time of CPR and improve over time.

Background The metastatic brain tumor is the most common brain tumor. The aim of this study was to demonstrate the clinicopathological and molecular pathologic features of brain metastases (BM). Methods A total of 269 patients were diagnosed with BM through surgical resection at Seoul St. Mary’s Hospital from January 2010 to March 2020. We reviewed the clinicopathological features and molecular status of primary and metastatic brain tissues using immunohistochemistry and molecular pathology results. Results Among 269 patients, 139 males and 130 females were included. The median age of primary tumor was 58 years (range, 13 to 87 years) and 86 patients (32.0%) had BM at initial presentation. Median BM free interval was 28.0 months (range, 1 to 286 months). The most frequent primary site was lung 46.5% (125/269), and followed by breast 15.6% (42/269), colorectum 10.0% (27/269). Epidermal growth factor receptor (EGFR) mutation was found in 50.8% (32/63) and 58.0% (40/69) of lung primary and BM, respectively. In both breast primary and breast cancer with BM, luminal B was the most frequent subtype at 37.9% (11/29) and 42.9% (18/42), respectively, followed by human epidermal growth factor receptor 2 with 31.0% (9/29) and 33.3% (14/42). Triple-negative was 20.7% (6/29) and 16.7% (7/42), and luminal A was 10.3% (3/29) and 7.1% (3/42) of breast primary and BM, respectively. In colorectal primary and colorectal cancer with BM, KRAS mutation was found in 76.9% (10/13) and 66.7% (2/3), respectively. Conclusions We report the clinicopathological and molecular pathologic features of BM that can provide useful information for understanding the pathogenesis of metastasis and for clinical trials based on the tumor’s molecular pathology.

Coronavirus disease 2019 (COVID-19) has strained healthcare systems worldwide. Predicting COVID-19 severity could optimize resource allocation, like oxygen devices and intensive care. If machine learning model could forecast the severity of COVID-19 patients, hospital resource allocation would be more comfortable. This study evaluated machine learning models using electronic records from 3,996 COVID-19 patients to forecast mild, moderate, or severe disease up to 2 days in advance. A deep neural network (DNN) model achieved 91.8% accuracy, 0.96 AUROC, and 0.90 AUPRC for 2-day predictions, regardless of disease phase. Tree-based models like random forest achieved slightly better metrics (random forest: 94.1% of accuracy, 0.98 AUROC, 0.95 AUPRC; Gradient boost: 94.1% of accuracy, 0.98 AUROC, 0.94 AUPRC), prioritizing treatment factors like steroid use. However, the DNN relied more on fixed patient factors like demographics and symptoms in aspect to SHAP value importance. Since treatment patterns vary between hospitals, the DNN may be more generalizable than tree-based models (random forest, gradient boost model). The results demonstrate accurate short-term forecasting of COVID-19 severity using routine clinical data. DNN models may balance predictive performance and generalizability better than other methods. Severity predictions by machine learning model could facilitate resource planning, like ICU arrangement and oxygen devices.

BackgroundThe coronavirus disease (COVID-19) pandemic has significantly strained global healthcare, particularly in the management of patients requiring mechanical ventilation (MV) and continuous renal replacement therapy (CRRT). This study investigated the characteristics and prognoses of these patients.MethodsThis multicenter retrospective cohort study gathered data from patients with COVID-19 across 26 medical centers. Logistic analysis was used to identify the factors associated with CRRT implementation.ResultsOf the 640 patients with COVID-19 who required MV, 123 (19.2%) underwent CRRT. Compared to the non-CRRT group, the CRRT group was older and exhibited higher sequential organ failure assessment scores. The incidence of hypertension, diabetes, cardiovascular disease, chronic neurological disease, and chronic kidney disease was also higher in the CRRT group. Moreover, the CRRT group had higher intensive care unit (ICU) (75.6% vs. 26.9%, p < 0.001) and in-hospital (79.7% vs. 29.6%, p < 0.001) mortality rates. CRRT implementation was identified as an independent risk factor for both ICU mortality (hazard ratio [HR]:1.833, 95% confidence interval [CI]:1.342-2.505, p < 0.001) and in-hospital mortality (HR: 2.228, 95% CI: 1.648-3.014, p < 0.001). Refractory respiratory failure (n = 99, 19.1%) was the most common cause of death in the non-CRRT death group, and shock with multi-organ failure (n = 50, 40.7%) was the most common cause of death in the CRRT death group. Shock with multi-organ failure and cardiac death were significantly more common in the CRRT death group, compared to non-CRRT death group.ConclusionThis study indicates that CRRT is associated with higher ICU and in-hospital mortality rates in patients with COVID-19 who require MV. Notably, the primary cause of death in the CRRT group was shock with multi-organ failure, emphasizing the severe clinical course for these patients, while refractory respiratory failure was most common in non-CRRT patients.

[This corrects the article DOI: 10.1371/journal.pone.0161231.].

Purpose: Pegfilgrastim is a widely used long-acting granulocyte colony-stimulating factor (G-CSF) that prevents febrile neutropenia (FN) in patients with breast cancer receiving chemotherapy. This study aimed to evaluate the incidence of chemotherapy-related FN events and other adverse events (AEs) during chemotherapy in Korean patients with breast cancer treated with pegfilgrastim as secondary prophylactic support. Materials and methods: This was a multicenter, open-label, prospective, observational study. A total of 1255 patients were enrolled from 43 institutions. The incidence of FN was evaluated as the primary endpoint. The secondary endpoints included (1) incidence of bone pain, (2) proportion of patients with a relative dose intensity (RDI) of ≥85%, and (3) proportion of patients with AE. Results: Pegfilgrastim administration reduced FN by 11.8–1.6%. The highest incidence of bone pain was observed at the time point of the 1st day after the administration and mild bone pain was the most common of all bone pain severity. The mean RDI was 98.5 ± 7.3%, and the proportion of the patients with and RDI≥85% was 96.9% (1169/1233). AEs were reported in 52.6% of the patients, and serious drug reactions occurred in only 0.7%. Conclusion: The use of pegfilgrastim as secondary prophylaxis was effective and safe for preventing FN in patients with breast cancer who were treated with chemotherapy.

Background Benign bladder tumors are rare disease entities, and insufficient studies have assessed their epidemiological characteristics. The authors investigated the prevalence of benign bladder tumors by retrospectively investigating pathology reports of transurethral resection of bladder tumor (TURBT) procedures over the past 20 years. Methods We analyzed 1,674 pathology reports of TURBT conducted in 1,160 patients from January 1, 2000, to April 30, 2022. The prevalence of benign tumors and histological classification according to the presence of primary (group 1) and recurrent (group 2) bladder lesions were retrospectively investigated. Results The mean age of patients was 65.2±11.5 years, and 1,284 cases (79.1%) were in men. Benign bladder tumors comprised 278 cases (248 patients) accounting for about 17.1% of the total TURBT cases (278/1,624). Furthermore, 184 patients (16.0%, 184/1,147) belonged to group 1 and 78 patients (27.4%, 78/285) belonged to group 2. Among all benign lesions that underwent TURBT, cystitis was the most common (41.0%, 114/278), and this rate was higher in group 2 (64/184 [34.8%] vs. 50/94 [53.2%], p

Abstract Background During the novel coronavirus disease-2019 pandemic, a considerable number of pneumothorax (PNX)/pneumomediastinum (PNM) associated with COVID-19 have been reported, and the incidence is higher in critically ill patients. Despite using a protective ventilation strategy, PNX/PNM still occurs in patients on invasive mechanical ventilation (IMV). This matched case–control study aims to identify the risk factors and clinical characteristics of PNX/PNM in COVID-19. Methods This retrospective study enrolled adult patients with COVID-19, admitted to a critical care unit from March 1, 2020, to January 31, 2022. COVID-19 patients with PNX/PNM were compared, in a 1–2 ratio, to COVID-19 patients without PNX/PNM, matched for age, gender, and worst National Institute of Allergy and Infectious Diseases ordinal scale. Conditional logistic regression analysis was performed to assess the risk factors for PNX/PNM in COVID-19. Results 427 patients with COVID-19 were admitted during the period, and 24 patients were diagnosed with PNX/PNM. Body mass index (BMI) was significantly lower in the case group (22.8 kg/m2 and 24.7 kg/m2; P = 0.048). BMI was statistically significant risk factor for PNX/PNM in univariate conditional logistic regression analysis [odds ratio (OR), 0.85; confidence interval (CI), 0.72–0.996; P = 0.044]. For patients on IMV support, univariate conditional logistic regression analysis showed the statistical significance of the duration from symptom onset to intubation (OR, 1.14; CI, 1.006–1.293; P = 0.041). Conclusions Higher BMI tended to show a protective effect against PNX/PNM due to COVID-19 and delayed application of IMV might be a contributive factor for this complication.

Abstract Although the association of nonalcoholic fatty liver disease (NAFLD) with obesity or sarcopenia is known, few studies have investigated the combined effect of various body composition parameters on the risk of NAFLD. Thus, the aim of this study was to evaluate effects of interactions between various body composition parameters, including obesity, visceral adiposity, and sarcopenia, on NAFLD. Data of subjects who underwent health checkups between 2010 and December 2020 were retrospectively analyzed. Body composition parameters including appendicular skeletal muscle mass (ASM) and visceral adiposity were assessed using bioelectrical impedance analysis. Sarcopenia was defined as ASM/weight beyond two standard deviations below the gender-specific mean for healthy young adults. NAFLD was diagnosed using hepatic ultrasonography. Interaction analyses, including relative excess risk due to interaction (RERI), synergy index (SI), and attributable proportion due to interaction (AP), were performed. Among a total of 17,540 subjects (mean age: 46.7 years, 49.4% males), the prevalence of NAFLD was 35.9%. The odds ratio (OR) of interaction between obesity and visceral adiposity affecting NAFLD was 9.14 (95% CI: 8.29–10.07). The RERI was 2.63 (95% CI: 1.71–3.55), SI was 1.48 (95% CI: 1.29–1.69) and AP was 29%. The OR of interaction between obesity and sarcopenia affecting NAFLD was 8.46 (95% CI: 7.01–10.21). The RERI was 2.21 (95% CI: 0.51–3.90). SI was 1.42(95% CI: 1.11–1.82) and AP was 26%. The OR of interaction between sarcopenia and visceral adiposity affecting NAFLD was 7.25 (95% CI: 6.04–8.71), however, there was no significant additive interaction with RERI = 0.87 (95% CI: −0.76 to 2.51). Obesity, visceral adiposity, and sarcopenia were found to be positively associated with NAFLD. Obesity, visceral adiposity, and sarcopenia were found to have additive interaction effects on NAFLD.

Background/Aims There have been little research on the cancer risks of patients with Peutz-Jeghers syndrome (PJS) in Korea. We aimed to investigate the clinical features of PJS patients and their cancer incidence rate. Methods Patients with PJS from nine medical centers were enrolled. In those patients diagnosed with cancer, data obtained included the date of cancer diagnosis, the tumor location, and the cancer stage. The cumulative risks of gastrointestinal cancers and extra-gastrointestinal cancers were calculated using the Kaplan-Meier method. Results A total of 96 PJS patients were included. The median age at diagnosis of PJS was 23.4 years. Cancer developed in 21 of the 96 patients (21.9%). The age of PJS diagnosis was widely distributed (0.9 to 72.4 years). The most common cancers were gastrointestinal cancer (n = 12) followed by breast cancer (n = 6). The cumulative lifetime cancer risk was calculated to be 62.1% at age 60. The cumulative lifetime gastrointestinal cancer risk was 47.1% at age 70. The cumulative lifetime extra-gastrointestinal cancer risk was 40.3% at age 60. Conclusions PJS onset may occur at any age and the risks of gastrointestinal and extra-gastrointestinal cancer are high. Thorough surveillance of PJS patients for malignancies is vital.

Background Alternative complement pathway dysregulation plays a key role in glomerulonephritis (GN) and is associated with C3 deposition. Herein, we examined pathological and clinical differences between cases of primary GN with C3-dominant (C3D-GN) and nondominant (C3ND-GN) deposition. Methods We extracted primary GN data from the Korean GlomeruloNEphritis sTudy (KoGNET). C3D-GN was defined as C3 staining two grades greater than C1q, C4, and immunoglobulin via immunofluorescence analysis. To overcome a large difference in the number of patients between the C3D-GN and C3ND-GN groups (31 vs. 9,689), permutation testing was used for analysis. Results The C3D-GN group exhibited higher serum creatinine (p ≤ 0.001), a greater prevalence of estimated glomerular filtration rate of

Abstract Background Women from Asian and western countries have vastly different ages of onset of breast cancer, with the disease tending to occur at an older age in the West. Through an investigation of the patterns of old-onset breast cancer (OBC) in Korean women, we aimed to identify the characteristics of Korean OBC and evaluate whether these patterns are changing in relation to increasing westernization. Methods This study retrospectively evaluated 102,379 patients who underwent surgical treatment of primary breast cancer between January 1, 2000 and December 31, 2013 in Korea. We used hospital -based breast cancer registry and analyzed data from these patients using multiple linear regression analysis to compare the characteristics and chronologically changing patterns between OBC (70 years of age or older) and non-OBC (40–69 years of age) patients in Korea. Results A total of 6% of the 102,379 patients had OBC. Overall, OBC had more favorable biological features, such as a higher incidence of luminal A subtype, than did non-OBC, except for a higher incidence rate of triple-negative breast cancer (TNBC). However, OBC also presented with a higher overall disease stage, including higher T and M stages. Although the incidence rates of both OBC and non-OBC have increased overtime, the relative proportion of OBC patients has slightly increased, whereas that of non-OBC has slightly decreased. The increase in the incidence of both OBC and non-OBC was primarily due to the luminal A subtype. Conclusions Based on a hospital-based registry, overall, Korean OBC had favorable biological features but showed a higher rate of TNBC and advanced cancer stages. The incidence trend of breast cancer in Korea is slowly shifting toward an older age at onset, largely due to the luminal A subtype. Our results may provide novel insights into OBC in Asia, and aid in the development of optimal management of the disease in Asia. Trial registration Retrospectively registered.

Abstract Glioblastoma (GBM) is a highly vascular malignant brain tumor that overexpresses vascular endothelial growth factor (VEGF) and phosphofructokinase 1 platelet isoform (PFKP), which catalyzes a rate-limiting reaction in glycolysis. However, whether PFKP and VEGF are reciprocally regulated during GBM tumor growth remains unknown. Here, we show that PFKP can promote EGFR activation-induced VEGF expression in HIF-1α-dependent and -independent manners in GBM cells. Importantly, we demonstrate that EGFR-phosphorylated PFKP Y64 has critical roles in both AKT/SP1-mediated transcriptional expression of HIF-1α and in the AKT-mediated β-catenin S552 phosphorylation, to fully enhance VEGF transcription, subsequently promoting blood vessel formation and brain tumor growth. Levels of PFKP Y64 phosphorylation in human GBM specimens are positively correlated with HIF-1α expression, β-catenin S552 phosphorylation, and VEGF expression. Conversely, VEGF upregulates PFKP expression in a PFKP S386 phosphorylation-dependent manner, leading to increased PFK enzyme activity, aerobic glycolysis, and proliferation in GBM cells. These findings highlight a novel mechanism underlying the mutual regulation that occurs between PFKP and VEGF for promoting GBM tumor growth and also suggest that targeting the PFKP/VEGF regulatory loop might show therapeutic potential for treating GBM patients.

The oral sulfate tablet (OST), commercially available as Orafang® (Pharmbio Korea Co., Seoul, Korea) in Korea, is being used increasingly because of its bowel-cleansing efficacy, safety, and tolerability in adults undergoing colonoscopy. Other bowel cleansing agents, such as polyethylene glycol and sodium picosulfate/magnesium citrate, can cause plasma volume depletion and electrolyte disturbances, such as hyponatremia. On the other hand, the OST has never been reported to cause hyponatremia in Korea. To our knowledge, the authors experienced the first case of hyponatremic seizure in an 81-year-old woman to whom an OST was administered for bowel preparation before a colonoscopy. After ingesting the OST, she presented with seizure, confusion, and dyspnea. Upon arrival, her serum sodium level was 120 mEq/L, and the urine osmolality and sodium levels were 449 mOsm/kg and 253 mOsm/kg, respectively; chest imaging suggested pulmonary edema. The associated symptoms disappeared following treatment with an intravenous injection of normal saline and 3% NaCl to normalize the sodium level. This case shows that the OST can cause hyponatremia and other severe complications related to hyponatremia.

Abstract Existing data for the association between late-life body mass index (BMI) and the risk of Alzheimer’s disease (AD) in the underweight population are limited with conflicting results. A large population-based cohort study of 148,534 individuals aged ≥ 65 years who participated in the national health screening program from 2002 to 2005 was performed using the Korean National Health Insurance Service-Senior cohort database 2006–2015. The risk of AD according to BMI category (kg/m2) in Asians was evaluated using a multivariable Cox regression model, after adjustments for age, sex, lifestyle, low-income status, and comorbidities. To evaluate the association between BMI and AD risk, the underweight population was further subdivided according to the degree of thinness. During the 10-year follow-up period, 22,279 individuals developed AD. Relative to the normal-weight population, the estimated adjusted hazard ratio (HR) for incident AD in the underweight, overweight, and obese populations was 1.17 (95% confidence interval [CI], 1.09–1.24), 0.90 (0.87–0.93), and 0.83 (0.80–0.85), respectively. In the underweight population, AD risk increased as the degree of thinness increased (p for the trend,

Abstract In studies evaluating the association between body mass index (BMI) and risk of tuberculosis (TB), the data for the underweight population has been limited and results were conflicting. Our study aimed to evaluate whether being underweight increases the risk of TB using a nationwide representative sample from the Republic of Korea. A large population-based cohort study of over ten million subjects who participated in the health screening in 2010 was performed using the Korean National Health Insurance database 2010–2017. We evaluated the incidence and risk of TB by BMI category (kg/m2) for Asians using a multivariable Cox regression model, adjusting for age, sex, smoking, alcohol consumption, regular exercise, low-income state, and underlying hypertension, diabetes mellitus, and dyslipidemia. To evaluate the association between BMI and TB risk, the underweight population was further subdivided according to the degree of thinness. During 70,063,154.3 person-years of follow-up, 52,615 of 11,135,332 individuals developed active TB with an incidence of 0.75 per 1000 person-years. Overall, there was a log-linear inverse relationship between TB incidence and BMI, within the BMI range of 15–30 kg/m2 (R2 = 0.95). The estimated adjusted hazard ratio (HR) for incident TB in the underweight population (BMI

Abstract Background Papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer, and its incidence has increased. Lateral lymph node metastasis (LLNM) implies a worse prognosis than central lymph node metastasis, with a higher recurrence rate and decreased disease-free survival. The 2015 American Thyroid Association guidelines recommend compartmental node dissection in patients with LLNM to reduce the risk of recurrence and mortality. The purpose of this study was to identify the risk factors for level V lymph node (LN) metastasis in patients with N1b papillary thyroid cancer (PTC). Methods A total of 110 consecutive patients who underwent total thyroidectomy with lateral neck dissection for PTC between April 2016 and April 2022 were retrospectively enrolled. Based on level V metastasis, 94 patients were divided into two groups, and their clinicopathological characteristics were compared. Univariable analysis were used to assess the factors associated with level V metastasis. Spearman correlation analysis were used to assess the correlation between tumors and LN. The receiver operating characteristic (ROC) curve was used to determine the optimal cutoff value for the number of metastatic LNs at each level for level V metastasis. Results The number of metastatic LNs and lymph node ratio (LNR) in level II were significantly associated with level V metastasis (P = 0.011 and 0.001, respectively). The number of metastatic LNs in level II and those in the total number of levels correlated with the number of metastatic LNs in level V (rho = 0.331, 0.325, and P = 0.001, 0.001, respectively). The cutoff value for the number of metastatic LNs in level II was defined as 2.5 (area under the curve = 0.757, sensitivity = 50%, specificity = 82.5%, 95% confidence interval [CI] 0.626–0.889, P = 0.002). Simultaneous 3-level metastasis (level II, III, and IV) and 3-level with ≥ 2.5 metastatic LNs in level II were significantly associated with level V metastasis (P = 0.003 and 0.002). Conclusions The number of metastatic LNs and LNR in level II, simultaneous 3-level metastasis (level II, III, and IV), and 3-level with ≥ 2.5 metastatic LNs in level II were significantly associated with level V metastasis. (P = 0.011, 0.001, 0.003, and 0.002, respectively). In the future, larger-scale multi-institutional studies were needed to find out predictors for level V metastasis.

Abstract Background Probiotic starters can improve the flavor profile, texture, and health-promoting properties of fermented foods. Tetragenococcus halophilus is a halophilic lactic acid bacterium that is a candidate starter for high-salt fermented foods. However, the species is known to produce biogenic amines, which are associated with neurotoxicity. Here, we report a probiotic starter strain of T. halophilus, EFEL7002, that is suitable for use in high-salt fermentation. Results EFEL7002 was isolated from Korean meju (fermented soybean) and identified as T. halophilus, with 99.85% similarity. The strain is safe for use in food as it is a non-hemolytic and non-biogenic amine producer. EFEL7002 is tolerant to gastrointestinal conditions and can adhere to Caco-2 cells. This strain showed antioxidant, anti-inflammatory, and protective effects against the human gut epithelial barrier. EFEL7002 grew well in media containing 0–18% NaCl showing maximum cell densities in 6% or 12% NaCl. Conclusions T. halophilus EFEL7002 can be used as a health-promoting probiotic starter culture for various salty fermented foods.

Abstract We aimed to describe the clinical features of lymphangioleiomyomatosis (LAM) in Korean patients and identify factors associated with progressive disease (PD). Clinical features of 54 patients with definite or probable LAM from 2005 to 2018 were retrospectively analysed. Common features were pneumothorax (66.7%) and abdominal lymphadenopathy (50.0%). Twenty-three (42.6%) patients were initially treated with mechanistic target of rapamycin (mTOR) inhibitors. Lung transplantation (LT) was performed in 13 (24.1%) patients. Grouped based on the annual decline in forced expiratory volume in 1 s (FEV1) from baseline and LT, 36 (66.7%) patients exhibited stable disease (SD). All six deaths (11.1%) occurred in PD. Proportion of SD was higher in those treated initially with mTOR inhibitors than in those under observation (p = 0.043). Univariate analysis revealed sirolimus use, and baseline forced vital capacity, FEV1, and diffusing capacity of the lungs for carbon monoxide are associated with PD. Multivariate analysis showed that only sirolimus use (odds ratio 0.141, 95% confidence interval 0.021–0.949, p = 0.044) reduced PD. Kaplan–Meier analysis estimates overall survival of 92.0% and 74.7% at 5 and 10 years, respectively. A considerable proportion of LAM patients remain clinically stable without treatment. LT is an increasingly viable option for patients with severe lung function decline.

Abstract Antibiotic resistance ranks among the top threats to humanity. Due to the frequent use of antibiotics, society is facing a high prevalence of multidrug resistant pathogens, which have managed to evolve mechanisms that help them evade the last line of therapeutics. An alternative to antibiotics could involve the use of bacteriophages (phages), which are the natural predators of bacterial cells. In earlier times, phages were implemented as therapeutic agents for a century but were mainly replaced with antibiotics, and considering the menace of antimicrobial resistance, it might again become of interest due to the increasing threat of antibiotic resistance among pathogens. The current understanding of phage biology and clustered regularly interspaced short palindromic repeats (CRISPR) assisted phage genome engineering techniques have facilitated to generate phage variants with unique therapeutic values. In this review, we briefly explain strategies to engineer bacteriophages. Next, we highlight the literature supporting CRISPR‐Cas9‐assisted phage engineering for effective and more specific targeting of bacterial pathogens. Lastly, we discuss techniques that either help to increase the fitness, specificity, or lytic ability of bacteriophages to control an infection.

Background/Aims: Previous studies have reported the protective effects of tauroursodeoxycholic acid (TUDCA) on gastric epithelial cells in some animal models, but the precise mechanisms are unclear. This study examined the effects of TUDCA on NF-κB signaling in gastric epithelial cells. Moreover, the protective effects of TUDCA in experimental gastritis models induced by ethanol and NSAID were evaluated and compared with ursodeoxycholic acid (UDCA). Methods: After a pretreatment with TUDCA or UDCA, human gastric epithelial MKN-45 cells were stimulated with tumor necrosis factor (TNF)-α to activate NF-κB signaling. A real-time PCR (RT-PCR) for human interleukin (IL)-1 mRNA was performed. An electrophoretic mobility shift assay (EMSA) and immunoblot analyses were carried out. In murine models, after a pretreatment with TUDCA or UDCA, ethanol and indomethacin were administered via oral gavage. Macroscopic and microscopic assessments were performed to evaluate the preventive effects of TUDCA and UDCA on murine gastritis. Results: A pretreatment with TUDCA downregulated the IL-1α mRNA levels in MKN-45 cells stimulated with TNF-α, as assessed by RT-PCR. As determined using EMSA, a pretreatment with TUDCA reduced the TNF-α-induced NF-κB DNA binding activity. A pretreatment with TUDCA inhibited IκBα phosphorylation induced by TNF-α, as assessed by immunoblot analysis. TUDCA attenuated the ethanol-induced and NSAID-induced gastritis in murine models, as determined macroscopically and microscopically. Conclusions: TUDCA inhibited NF-κB signaling in gastric epithelial cells and ameliorated ethanol- and NSAID-induced gastritis in murine models. These results support the potential of TUDCA for the prevention of gastritis in humans.

Abstract We aimed to assess the relationship between lifestyle-related variables, metabolic syndrome, and lower urinary tract symptoms (LUTS) in men ≥ 40 years. We also assessed the impact of these variables on quality of life. From 2014 to 2020, 5355 men who underwent health check-ups with I-PSS questionnaires at our institute were included in the analysis. The impact of LUTS on sleep disorders and moderate to severe degrees of stress were assessed. Multivariate analysis was performed to determine the variables associated with LUTS and prostate volume. Moderate and severe LUTS were present in 1317 (24.6%) and 211 (3.9%) men, respectively. Moderate and severe LUTS were significantly associated with the presence of sleep disorders and stress. On multivariable analysis, age, amount of life-long smoking, marital status, income, job, and decreased HDL-cholesterol were associated with the presence of moderate to severe LUTS. Although older age and the amount of life-long smoking was associated with both voiding and storage sub-score, socioeconomic status, including marital status and income were only associated with storage sub-score. In men ≥ 40 years, stable socioeconomic status, in addition to older age, and life-long smoking amount are associated with the presence of moderate to severe LUTS, which worsens sleep quality and stress level, by worsen storage sub-score.

Abstract The programmed cell death ligand 1 (PD-L1) and its receptor programmed cell death 1 (PD-1) deliver inhibitory signals to regulate immunological tolerance during immune-mediated diseases. However, the role of PD-1 signaling and its blockade effect on human dental pulp stem cells (hDPSCs) differentiation into the osteo-/odontogenic lineage remain unknown. We show here that PD-L1 expression, but not PD-1, is downregulated during osteo-/odontogenic differentiation of hDPSCs. Importantly, PD-L1/PD-1 signaling has been shown to negatively regulate the osteo-/odontogenic differentiation of hDPSCs. Mechanistically, depletion of either PD-L1 or PD-1 expression increased ERK and AKT phosphorylation levels through the upregulation of Ras enzyme activity, which plays a pivotal role during hDPSCs osteo-/odontogenic differentiation. Treatment with nivolumab (a human anti-PD-1 monoclonal antibody), which targets PD-1 to prevent PD-L1 binding, successfully enhanced osteo-/odontogenic differentiation of hDPSCs through enhanced Ras activity-mediated phosphorylation of ERK and AKT. Our findings underscore that downregulation of PD-L1 expression accompanies during osteo-/odontogenic differentiation, and hDPSCs-intrinsic PD-1 signaling inhibits osteo-/odontogenic differentiation. These findings provide a significant basis that PD-1 blockade could be effective immunotherapeutic strategies in hDPSCs-mediated dental pulp regeneration.