Background: This study aims to compare the effects of short- and intermediate-acting erythropoiesis-stimulating agents (ESAs) on hemoglobin (Hb) variability in patients undergoing maintenance hemodialysis. Methods: This retrospective cohort study included 119 patients who were classified into two groups based on ESA type: short-acting ESA (epoetin alfa/beta [EPO], n=48) and intermediate-acting ESA (darbepoetin alfa [DPO], n=71). Hb levels were measured 11 times at 4-week intervals from ESA therapy initiation to 40 weeks of follow-up. This study used established metrics from previous research, including standard deviation (SD), coefficient of variation (CV), and residual SD, to quantify Hb variability. Results: Over the 40-week study period with 4-week measurement intervals, mean Hb levels were comparable between the two ESA groups. In the EPO and DPO groups, SD was 0.67±0.19 g/dL and 0.69±0.22 g/dL, respectively (p=0.516), CV was 0.06±0.02 and 0.07±0.02, respectively (p=0.480), and residual SD was 0.73±0.21 g/dL and 0.76±0.26 g/dL, respectively (p=0.463). No significant differences in Hb variability were observed between the groups over 40 weeks using SD, CV, and residual SD. Conclusion This retrospective cohort study showed comparable mean Hb levels and Hb variability indices between groups. With respect to Hb variability, the findings reveal no clear basis for prioritizing either short-acting or intermediate-acting ESA.

Background: Obesity is a well-known risk factor for chronic kidney disease and its progression. However, the impact of obesity on the renal function of the elderly population is uncertain. We investigated the association between obesity and renal outcomes in the elderly. Methods: We analyzed 130,504 participants from the Korean National Health Insurance Service-Senior cohort. Obesity was classified according to body mass index (BMI), sex-specific waist circumference (WC), and the presence of metabolic syndrome. The primary outcome was renal function decline, defined as a decline in the estimated glomerular filtration rate (eGFR) of at least 50% from baseline or new-onset end-stage renal disease. Results: During a follow-up period of 559,531.1 person-years (median, 4.3 years), 2,486 participants (19.0%; incidence rate of 4.44 per 1,000 person-years) showed renal function decline. A multivariate Cox proportional hazards model revealed that BMI/WC was not associated with renal function decline. However, the group with metabolic syndrome had a significantly increased risk of renal function decline compared to the group without metabolic syndrome (adjusted hazard ratio [HR], 1.24; 95% confidence interval [CI], 1.13–1.36). Compared with the non-metabolic syndrome group, the adjusted HRs (95% CI) for participants with one through five components were 0.96 (0.84–1.11), 1.10 (0.96–1.27), 1.24 (1.06–1.45), 1.37 (1.12–1.66), and 1.99 (1.42–2.79), respectively (p for trend < 0.001). Conclusion In elderly Korean adults, metabolic syndrome and the number of its components were associated with a higher risk of renal function decline, but BMI or WC was not significant.

Purpose: Adjuvant chemotherapy (AC) is recommended for muscle-invasive or lymph node-positive upper urinary tract urothelial carcinoma (UTUC) after radical nephroureterectomy (RNU). However, disease recurrences are frequently observed in pT1 disease, and AC may increase the risk of overtreatment in pT2 UTUC patients. This study aimed to validate a risk-adapted scoring model for selecting UTUC patients with ≤pT2 disease who would benefit from AC. Materials and Methods: We retrospectively analyzed 443 ≤pT2 UTUC patients who underwent RNU. A risk-adapted scoring model was applied, categorizing patients into low- or high-risk groups. Recurrence-free survival (RFS) and cancer-specific survival (CSS) were analyzed according to risk group. Results: Overall, 355 patients (80.1%) and 88 patients (19.9%) were categorized into the low- and high-risk groups, respectively, with the latter having higher pathological stages, concurrent carcinoma in situ, and synchronous bladder tumors. Disease recurrence occurred in 45 patients (10.2%), among whom 19 (5.4%) and 26 (29.5%) belonged to the low- and high-risk groups, respectively (p<0.001). High-risk patients had significantly shorter RFS (64.3% vs. 93.6% at 60 months; hazard ratio [HR] 13.66; p<0.001) and worse CSS (80.7% vs. 91.5% at 60 months; HR 4.25; p=0.002). Multivariate analysis confirmed that pT2 stage and the high-risk group were independent predictors of recurrence and cancer-specific death (p<0.001). Decision curve analysis for RFS showed larger net benefits with our model than with the T stage model. Conclusions The risk-adapted scoring model effectively predicts recurrence and identifies optimal candidates for AC post RNU in non-metastatic UTUC.

Objective: Primary frozen shoulder causes significant pain and progressively restricts shoulder movements. Diagnosis is made clinically based on patient history and physical examination. Management is mainly non-invasive owing to its self-limiting clinical course. However, clinical practice guidelines for frozen shoulder have not yet been developed in Korea. The developed guidelines aim to provide evidence-based recommendations for the diagnosis and treatment of frozen shoulder. Methods: A guideline development committee reviewed the literature from four databases (PubMed, Embase, Cochrane Library, and KMbase). Using the Population, Intervention, Comparator, and Outcome (PICO) framework, the committee formulated two backgrounds and 16 key questions to address common clinical concerns. Recommendations were made using the Grading of Recommendations, Assessment, Development, and Evaluation framework. Results: Diabetes, thyroid disease, and dyslipidemia significantly increase the risk of developing a frozen shoulder. Although frozen shoulder is often self-limiting, some patients may experience long-term functional disabilities. Ultrasound and magnetic resonance imaging should be used as adjunctive tools alongside clinical diagnosis, and rather than as independent diagnostic methods. Noninvasive approaches, such as medications, physical modalities, exercises, electrical stimulation, and manual therapy, may reduce pain and improve shoulder function. Other noninvasive interventions have limited evidence, and their application should be based on clinical judgment. Intra-articular steroid injections are recommended for treatment, and physiotherapy or hydrodilation with steroid injections can also be beneficial. Conclusion These guidelines provide evidence-based recommendations for diagnosing and treating primary frozen shoulder.

This study investigated the molecular mechanism of phenotypic switching of vascular smooth muscle cells (VSMCs), which play a crucial role in vascular remodeling using 9H-Carbazol-3-yl 4-aminobenzoate (CAB). CAB significantly attenuated platelet-derived growth factor (PDGF)-induced VSMC proliferation and migration. CAB suppressed PDGF-induced STAT3 activation by directly binding to the SH2 domain of STAT3. Downregulation of STAT3 phosphorylation by CAB attenuated CIAPIN1/JAK2/STAT3 axis through a decrease in CIAPIN1 transcription. Furthermore, abrogated CIAPIN1 decreased KLF4-mediated VSMC dedifferentiation and increased CDKN1B-induced cell cycle arrest and MMP9 suppression. CAB inhibited intimal hyperplasia in injury-induced neointima animal models by inhibition of the CIAPIN1/JAK2/STAT3 axis. However, CIAPIN1 overexpression attenuated CAB-mediated suppression of VSMC proliferation, migration, phenotypic switching, and intimal hyperplasia. Our study clarified the molecular mechanism underlying STAT3 inhibition of VSMC phenotypic switching and vascular remodeling and identified novel active CAB. These findings demonstrated that STAT3 can be a major regulator to control CIAPIN1/JAK2/STAT3 axis that may be a therapeutic target for treating vascular proliferative diseases.

Early mortality following hemodialysis initiation hinders survival improvement in older patients. This study aimed to develop a clinical risk model for predicting 6-month mortality after dialysis initiation in older Korean hemodialysis patients. Methods: We analyzed data from incident hemodialysis patients aged >70 years from the Korean Society of Geriatric Nephrology (KSGN) database. A prediction model was developed using multivariate logistic regression analysis and externally validated with independent datasets. Results: Among 1,751 incident hemodialysis patients, the 6-month mortality rate was 15.5%. Using multivariate logistic analysis, we constructed the KSGN score as an independent risk factor for 6-month mortality, and its components and score are as follows: old age at dialysis initiation (≥85 years, score 2); hypertension and renovascular disease as a primary etiology of end-stage kidney disease (ESKD) (score 1); malignancy history (yes, score 1); low serum albumin (<3.5 g/dL, score 1); hypertension treatment (yes, score –1); prepared vascular access on maintenance dialysis (arteriovenous fistula/arteriovenous graft, score –3). In the development cohort, the area under the curve (AUC) for the KSGN score was significantly higher than the Alberta Wick’s score (0.707 vs. 0.683, p = 0.001). In the validation cohort, the KSGN score’s performance was comparable to existing models. Conclusion: The KSGN score may be a valuable tool for predicting early mortality after dialysis initiation in older patients with ESKD, aiding in decision-making and management regarding dialysis initiation.

Viral load and the duration of viral shedding of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are important determinants of the transmission of coronavirus disease 2019.In this study, we examined the effects of viral doses on the lung and spleen of K18-hACE2 transgenic mice by temporal histological and transcriptional analyses. Approximately, 1×105 plaque-forming units (PFU) of SARS-CoV-2 induced strong host responses in the lungs from 2 days post inoculation (dpi) which did not recover until the mice died, whereas responses to the virus were obvious at 5 days, recovering to the basal state by 14 dpi at 1×102 PFU. Further, flow cytometry showed that number of CD8+ T cells continuously increased in 1×102 PFU-virusinfected lungs from 2 dpi, but not in 1×105 PFU-virus-infected lungs. In spleens, responses to the virus were prominent from 2 dpi, and number of B cells was significantly decreased at 1×105PFU; however, 1×102 PFU of virus induced very weak responses from 2 dpi which recovered by 10 dpi. Although the defense responses returned to normal and the mice survived, lung histology showed evidence of fibrosis, suggesting sequelae of SARS-CoV-2 infection. Our findings indicate that specific effectors of the immune response in the lung and spleen were either increased or depleted in response to doses of SARS-CoV-2. This study demonstrated that the response of local and systemic immune effectors to a viral infection varies with viral dose, which either exacerbates the severity of the infection or accelerates its elimination.

Background: A decline in masticatory function may indicate brain dysfunction related to dementia, but the relationship between masticatory function and dementia risk remains unclear. This study aimed to investigate whether masticatory function is associated with the risk of cognitive decline and dementia. Methods: Data were obtained from the nationwide prospective cohort study of randomly sampled community-dwelling Koreans aged ≥ 60 years. The 5,064 non-demented participants, whose number of chewing cycles per bite was assessed by clinical interview, were followed for 8 years with biennial assessments of cognitive performance and clinical diagnoses of all-cause dementia and Alzheimer’s disease (AD). Structural brain magnetic resonance imaging was collected from a subset of cohort participants and their spouses for imaging analyses. Results: Males who chewed ≥ 30 cycles/bite had faster decline in global cognition and memory function and were at higher risk for incident all-cause dementia (hazard ratio [HR], 2.91; 95% confidence interval [CI], 1.18–7.18) and AD (HR, 3.22; 95% CI, 1.14–9.11) compared to males with less than 10 cycles/bite. Additionally, increased chewing cycles in males were associated with reduced brain volume, particularly in regions involved in compensatory cognitive control of mastication. There was no significant association between chewing cycles and the risk of dementia or brain volume in females. Conclusion Older men who frequently chew their meals could be considered a notable population at risk for dementia who should be carefully assessed for their cognitive trajectories.

Objective: The Scales for Outcomes in Parkinson’s Disease–Cognition (SCOPA-Cog) was developed to assess cognition in patients with Parkinson’s disease (PD). In this study, we aimed to evaluate the validity and reliability of the Korean version of the SCOPACog (K-SCOPA-Cog). Methods: We enrolled 129 PD patients with movement disorders from 31 clinics in South Korea. The original version of the SCOPA-Cog was translated into Korean using the translation-retranslation method. The test–retest method with an intraclass correlation coefficient (ICC) and Cronbach’s alpha coefficient were used to assess reliability. Spearman’s rank correlation analysis with the Montreal Cognitive Assessment-Korean version (MOCA-K) and the Korean Mini-Mental State Examination (K-MMSE) were used to assess concurrent validity. Results: The Cronbach’s alpha coefficient was 0.797, and the ICC was 0.887. Spearman’s rank correlation analysis revealed a significant correlation with the K-MMSE and MOCA-K scores (r = 0.546 and r = 0.683, respectively). Conclusion Our results demonstrate that the K-SCOPA-Cog has good reliability and validity.

Calcific aortic valve disease (CAVD) is an uncommon disease in young adults, unless there is a congenital anomaly in the aortic valve. We report a case of CAVD identified during the autopsy of a 26-year-old male soldier who died in his room while sitting on a chair. Macroscopic examination revealed multiple nodules in the semilunar cusps of the aortic valve, and that the commissure of semilunar valve cusps was slightly fused. Under microscopic examination, fibrotic nodules with neovascularization were identified in the fibrosa layer of the aortic valve, although neither calcification nor chronic inflammation were identified in the fibrotic nodule. Mitral valve prolapse and left ventricular hypertrophy with interstitial fibrosis were also identified. Microscopic examination of CAVD typically shows calcified nodules in the fibrosa layer of the valve, but fibrosis alone, without calcification, can be observed in the early stage of the disease. Death from CAVD is rare in young adults, so careful examination must be taken not to misdiagnose this condition with rheumatic valvular disease, which is relatively common in this population.