Purpose: The aim of this study was to examine whether a combined exercise (EX), including aerobic, resistance, and inspiratory muscle training, reduces fatigue and dyspnea, improves physical fitness, and if increased physical fitness after exercise is associated with attenuating symptoms in young adults with mild long coronavirus disease (COVID) symptoms. Methods: Twenty-eight young adults (aged 23±4 years) with long COVID were randomly assigned to either the EX group (n=14), which underwent aerobic, resistance, and inspiratory muscle training three times per week for 8 weeks, or the control (CON) group (n=14). Symptoms of dyspnea and fatigue were assessed using self-report questionnaires.Cardiorespiratory fitness was directly measured during cardiopulmonary exercise testing, while muscle strength was measured by isokinetic muscle testing. These variables were measured before and after the exercise intervention. Results: Compared to the CON group, the EX group showed improvements in symptoms of fatigue and dyspnea, maximal oxygen consumption (VO2peak ), and peak torque, with significant interaction effects observed (p＜ 0.05). The EX group exhibited a mean difference of 2.9 mL/kg/min in VO2peak (95% confidence interval [CI], 1.8−4.0) and 13.0 Nm (95% CI, 6.1−19.8) in peak torque compared to the CON group (p＜0.05). Improvements in VO2peak were negatively associated with attenuations in both fatigue and dyspnea after the exercise intervention (p＜0.05). Conclusion These findings indicate that EX training can effectively alleviate symptoms and improve physical fitness in young adults with mild long COVID. Structured exercise training may serve as an effective intervention to improve the health of those with long COVID.

Purpose: This study elucidates the mechanism of the physiological effect of cannabidiol (CBD) by assessing its impact on lipopolysaccharide (LPS)-induced inflammation in RWPE-1 cells and prostatitis-induced by 17β-estradiol and dihydrotestosterone in a rat model, focusing on its therapeutic potential for chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). Materials and Methods: RWPE-1 cells were stratified in vitro into three groups: (1) controls, (2) cells with LPS-induced inflammation, and (3) cells with LPS-induced inflammation and treated with CBD. Enzyme-linked immunosorbent assays and western blots were performed on cellular components and supernatants after administration of CBD. Five groups of six Sprague–Dawley male rats were assigned: (1) control, (2) CP/CPPS, (3) CP/CPPS and treated with 50 mg/kg CBD, (4) CP/CPPS and treated with 100 mg/kg CBD, and (5) CP/CPPS and treated with 150 mg/kg CBD. Prostatitis was induced through administration of 17β-estradiol and dihydrotestosterone. After four weeks of CBD treatment, a pain index was evaluated, and prostate tissue was collected for subsequent histologic examination and western blot analysis. Results: CBD demonstrated efficacy in vivo for CP/CPPS and in vitro for inflammation. It inhibited the toll-like receptor 4 (TLR4)uclear factor-kappa B (NF-κB) pathway by activating the CB2 receptor, reducing expression of interleukin-6, tumor necrosis factor-alpha, and cyclooxygenase-2 (COX2) (p<0.01). CBD exhibited analgesic effects by activating and desensitizing the TRPV1 receptor. Conclusions CBD inhibits the TLR4/NF-κB pathway by activating the CB2 receptor, desensitizes the TRPV1 receptor, and decreases the release of COX2. This results in relief of inflammation and pain in patients with CP/CPPS, indicating CBD as a potential treatment for CP/CPPS.

Connective tissue disease (CTD), comprising a range of autoimmune disorders, is often accompanied by lung involvement, which can lead to life-threatening complications. The primary types of CTDs that manifest as interstitial lung disease (ILD) include rheumatoid arthritis, systemic sclerosis, Sjögren’s syndrome, mixed CTD, idiopathic inflammatory myopathies, and systemic lupus erythematosus. CTD-ILD presents a significant challenge in clinical diagnosis and management due to its heterogeneous nature and variable prognosis. Early diagnosis through clinical, serological, and radiographic assessments is crucial for distinguishing CTD-ILD from idiopathic forms and for implementing appropriate therapeutic strategies. Hence, we have reviewed the multiple clinical manifestations and diagnostic approaches for each type of CTD-ILD, acknowledging the diversity and complexity of the disease. The importance of a multidisciplinary approach in optimizing the management of CTD-ILD is emphasized by recent therapeutic advancements, which include immunosuppressive agents, antifibrotic therapies, and newer biological agents targeting specific pathways involved in the pathogenesis. Therapeutic strategies should be customized according to the type of CTD, the extent of lung involvement, and the presence of extrapulmonary manifestations. Additionally, we aimed to provide clinical guidance, including therapeutic recommendations, for the effective management of CTD-ILD, based on patient, intervention, comparison, outcome (PICO) analysis.

Background: Lung ultrasound (LUS) has proven valuable in the initial assessment of coronavirus disease 2019 (COVID-19), but its role in detecting pulmonary fibrosis following intensive care remains unclear. This study aims to assess the presence of pulmonary sequelae and fibrosis-like changes using LUS in survivors of severe COVID-19 pneumonia one month after discharge. Methods: We prospectively enrolled patients with severe COVID-19 who required mechanical ventilation in the intensive care unit (ICU) and conducted LUS assessments from admission to the outpatient visit after discharge. We tracked changes in key LUS findings and applied our proprietary LUS scoring system. To evaluate LUS accuracy, we correlated measured LUS values with computed tomography scores. Results: We evaluated B-line presence, pleural thickness, and consolidation in 14 eligible patients. The LUS scores exhibited minimal changes, with values of 19.1, 19.2, and 17.5 at admission, discharge, and the outpatient visit, respectively. Notably, the number of B-lines decreased significantly, from 1.92 at admission to 0.56 at the outpatient visit (p<0.05), while pleural thickness increased significantly, from 2.05 at admission to 2.48 at the outpatient visit (p≤0.05). Conclusion This study demonstrates that LUS can track changes in lung abnormalities in severe COVID-19 patients from ICU admission through to outpatient follow-up. While pleural thickening and B-line patterns showed significant changes, no correlation was found between LUS and high-resolution computed tomography fibrosis scores. These findings suggest that LUS may serve as a supplementary tool for assessing pulmonary recovery in severe COVID-19 cases.

Purpose: Emphysematous pyelonephritis (EPN) is a life-threatening disease requiring immediate treatment. This multicenter retrospective cohort study aimed to analyze the mortality rate and risk factors associated with EPN. Materials and Methods: Between January 2011 and February 2021, 217 patients diagnosed with EPN via computed tomography who visited 14 teaching hospitals were retrospectively analyzed. Clinical data, including age, sex, comorbidities, Huang and Tseng classification, hydronephrosis, acute kidney injury, blood and urine tests, surgical interventions, percutaneous drainage, and conservative treatments, were compared between the survival and death groups. Risk factors for mortality due to EPN were analyzed using univariate and multivariate methods. Results: The mean age of survivors and deceased patients was 67.8 and 69.0 years, respectively (p=0.136). The sex distribution (male/female) was 48/146 and 8/15, respectively (p=0.298). Of the 217 patients, 23 died, resulting in a mortality rate of 10.6%. In univariate analysis, the Huang and Tseng classification (p=0.004), platelet count (p=0.005), and acute kidney injury (p=0.007) were significantly associated with mortality from EPN. In multivariate analysis, only the Huang and Tseng classification (p=0.029) was identified as a risk factor. Mortality rates according to the Huang and Tseng classification were as follows: class I (5.88%), class II (7.50%), class IIIa (14.28%), class IIIb (25.00%), and class IV (23.07%). Conclusions EPN is associated with a high mortality rate. Among various clinical factors, the Huang and Tseng classification was the most significant indicator for predicting mortality.

Purpose: Cognitive behavioral therapy (CBT) has long been recognized as an effective treatment for depression and suicidality.Virtual reality (VR) technology is widely used for cognitive training for conditions such as anxiety disorder and post-traumatic stress disorder, but little research has considered VR-based CBT for depressive symptoms and suicidality. We tested the effectiveness and safety of a VR-based CBT program for depressive disorders. Materials and Methods: We recruited 57 participants from May 2022 through February 2023 using online advertisements. This multi-center, assessor-blinded, randomized, controlled exploratory trial used two groups: VR treatment group and treat as usual (TAU) group. VR treatment group received a VR mental health training/education program. TAU group received standard pharmacotherapy. Assessments were conducted at baseline, immediately after the 6-week treatment period, and 4 weeks after the end of the treatment period in each group. Results: Depression scores decreased significantly over time in both VR treatment and TAU groups, with no differences between the two groups. The suicidality score decreased significantly only in VR group. No group differences were found in the remission or response rate for depression, perceived stress, or clinical severity. No adverse events or motion sickness occurred during the VR treatment program. Conclusion VR CBT treatment for major depressive disorder has the potential to be equivalent to the gold-standard pharmacotherapy in reducing depressive symptoms, suicidality, and related clinical symptoms, with no difference in improvement found in this study. Thus, VR-based CBT might be an effective alternative to pharmacotherapy for depressive disorders.

Purpose: Rare diseases occur in <50 per 100000 people and require lifelong management. However, essential epidemiological data on such diseases are lacking, and a consecutive monitoring system across time and regions remains to be established. Standardized digital phenotypes are required to leverage an international data network for research on rare endocrine diseases. We developed digital phenotypes for rare endocrine diseases using the observational medical outcome partnership common data model. Materials and Methods: Digital phenotypes of three rare endocrine diseases (medullary thyroid cancer, hypoparathyroidism, pheochromocytoma/paraganglioma) were validated across three databases that use different vocabularies: Severance Hospital’s electronic health record from South Korea; IQVIA’s United Kingdom (UK) database for general practitioners; and IQVIA’s United States (US) hospital database for general hospitals. We estimated the performance of different digital phenotyping methods based on International Classification of Diseases (ICD)-10 in the UK and the US or systematized nomenclature of medicine clinical terms (SNOMED CT) in Korea. Results: The positive predictive value of digital phenotyping was higher using SNOMED CT-based phenotyping than ICD-10-based phenotyping for all three diseases in Korea (e.g., pheochromocytoma/paraganglioma: ICD-10, 58%–62%; SNOMED CT, 89%). Estimated incidence rates by digital phenotyping were as follows: medullary thyroid cancer, 0.34–2.07 (Korea), 0.13–0.30 (US); hypoparathyroidism, 0.40–1.20 (Korea), 0.59–1.01 (US), 0.00–1.78 (UK); and pheochromocytoma/paraganglioma, 0.95–1.67 (Korea), 0.35–0.77 (US), 0.00–0.49 (UK). Conclusion Our findings demonstrate the feasibility of developing digital phenotyping of rare endocrine diseases and highlight the importance of implementing SNOMED CT in routine clinical practice to provide granularity for research.

Purpose: To develop a machine learning (ML) classifier for predicting post-induction hypotension (PIH) in non-cardiac surgeries. Materials and Methods: Preoperative data and early vital signs were obtained from 3669 cases in the VitalDB database, an opensource registry. PIH was defined as sustained mean arterial pressure (MAP) <65 mm Hg within 20 minutes since induction or from induction to incision. Six different ML algorithms were used to create binary classifiers to predict PIH. The primary outcome was the area under the receiver operating characteristic curve (AUROC) of ML classifiers. Results: A total of 2321 (63.3%) cases exhibited PIH. Among ML classifiers, the random forest regressor and extremely gradient boosting regressor showed the highest AUROC, both recording a value of 0.772. Excluding these models, the light gradient boosting machine regressor showed the second highest AUROC [0.769; 95% confidence interval (CI), 0.767–0.771], followed by the gradient boosting regressor (0.768; 95% CI, 0.763–0.772), AdaBoost regressor (0.752; 95% CI, 0.743–0.761), and automatic relevance determination regression (0.685; 95% CI, 0.669–0.701). The top three important features were mean diastolic blood pressure (DBP), minimum MAP, and minimum DBP from anesthetic induction to tracheal intubation, and these features were lower in cases with PIH (all p<0.001). Conclusion ML classifiers exhibited moderate performance in predicting PIH, and have the potential for real-time prediction.

Background: s/Aims: Hepatocellular carcinoma (HCC) is the sixth most common cancer and second leading cause of cancer-related deaths in South Korea. This study evaluated the characteristics of Korean patients newly diagnosed with HCC in 2016-2018. Methods: Data from the Korean Primary Liver Cancer Registry (KPLCR), a representative database of patients newly diagnosed with HCC in South Korea, were analyzed. This study investigated 4,462 patients with HCC registered in the KPLCR in 2016-2018. Results: The median patient age was 63 years (interquartile range, 55-72). 79.7% of patients were male. Hepatitis B infection was the most common underlying liver disease (54.5%). The Barcelona Clinic Liver Cancer (BCLC) staging system classified patients as follows: stage 0 (14.9%), A (28.8%), B (7.5%), C (39.0%), and D (9.8%). The median overall survival was 3.72 years (95% confidence interval, 3.47-4.14), with 1-, 3-, and 5-year overall survival rates of 71.3%, 54.1%, and 44.3%, respectively. In 2016-2018, there was a significant shift toward BCLC stage 0-A and Child-Turcotte-Pugh liver function class A (P<0.05), although survival rates did not differ by diagnosis year. In the treatment group (n=4,389), the most common initial treatments were transarterial therapy (31.7%), surgical resection (24.9%), best supportive care (18.9%), and local ablation therapy (10.5%). Conclusions Between 2016 and 2018, HCC tended to be diagnosed at earlier stages, with better liver function in later years. However, since approximately half of the patients remained diagnosed at an advanced stage, more rigorous and optimized HCC screening strategies should be implemented.

Background: s/Aims: Radiofrequency ablation (RFA) is widely employed for managing recurrent hepatocellular carcinoma (HCC) following transarterial chemoembolization (TACE). However, local tumor progression (LTP) after treatment remains a significant challenge. This study evaluates the efficacy of saline-perfused bipolar RFA using twin internally cooled-perfusion (TICP) electrodes in managing recurrent HCC post-TACE. Methods: Between September 2017 and January 2019, 100 patients with 105 nodules (mean diameter, 1.6±0.5 cm) were prospectively enrolled. Bipolar RFA with TICP electrodes was performed under ultrasound-computed tomography/magnetic resonance fusion guidance. The primary outcome was the 2-year cumulative incidence of LTP. Results: The technical success and technique efficacy rates were 100% and 97%, respectively. During a median follow-up period of 34.0 months (range, 3-41), the estimated LTP rates were 13.3% at 1 year and 17.7% at 2 years. Progression-free survival rates were 37.8% and 27.7% at 1 year and 2 years, respectively. Conclusions Saline-perfused bipolar RFA using TICP electrodes demonstrates promising results for recurrent HCC after TACE, achieving high technical success and effective local tumor control rates.