Kidney and cardiovascular outcomes in older population with mildly to moderately decreased kidney function - A nationwide cohort study.

INTRODUCTION: Although the prevalence of chronic kidney disease (CKD) is increasing in the aging population, the clinical relevance of the CKD definition (glomerular filtration rate [GFR] < 60 ml/min/1.73 m2) in older populations remains debatable. We investigated the clinical outcomes in older populations with mildly to moderately decreased GFR (45-59 ml/min/1.73 m2, CKD stage 3A). METHODS: A total of 7,789,242 participants aged ≥ 40 years with estimated GFR (eGFR) ≥ 45 ml/min/1.73 m2 in national health screening examination from 2012 to 2017 were included in this retrospective cohort study using the Korean National Health Insurance Service database. The main outcomes included kidney failure, cardiovascular disease (CVD), and all-cause death. Cox regression hazard models were used to estimate the hazard ratios. RESULTS: The proportion of participants with eGFR 45-59 ml/min/1.73 m2 was 10.0% and 16.3% in the old (65-74 years) and very old (75 ≥ years) groups, respectively. Mildly to moderately decreased eGFR was associated with a higher risk of kidney failure, CVD, and all-cause death compared with eGFR 60-89 ml/min/1.73 m2 in the old and very old groups, regardless of proteinuria (adjusted hazard ratio [95% confidence interval] in the very old group without proteinuria: kidney failure 3.048 [2.495-3.722], CVD 1.103 [1.066-1.142], and all-cause death 1.172 [1.144-1.201]). CONCLUSION: Mildly to moderately decreased eGFR was associated with an increased risk of kidney failure, CVD, and all-cause death in the older population, regardless of proteinuria, suggesting the importance of appropriate monitoring and management in this population.

Natural Products and Their Neuroprotective Effects in Degenerative Brain Diseases: A Comprehensive Review.

As the global population ages, the incidence of neurodegenerative diseases such as Alzheimer's and Parkinson's is rapidly rising. These diseases present a significant public health challenge, as they severely impair cognitive and motor functions, ultimately leading to a substantial reduction in quality of life and placing a heavy burden on healthcare systems worldwide. Although several therapeutic agents have been developed to manage the symptoms of these diseases, their effectiveness is often limited, and there remains an urgent need for preventive strategies. Growing evidence indicates that bioactive compounds from natural products possess neuroprotective properties through antioxidant and anti-inflammatory effects, modulating key pathways such as phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) and brain-derived neurotrophic factor-tropomyosin receptor kinase B-cAMP response element-binding protein (BDNF-TrkB-CREB), which are crucial for neuronal survival. These compounds may also reduce amyloid-beta and tau pathology, as well as enhance cholinergic neurotransmission by inhibiting acetylcholinesterase activity. By targeting oxidative stress, neuroinflammation, and neurodegeneration, natural products offer a promising approach for both prevention and treatment. These findings suggest that natural products may be promising for preventing and treating neurodegenerative diseases. This review aims to explore the pathogenesis of neurodegenerative diseases, the limitations of current therapies, and the potential role of natural products as therapeutic agents.

Age at menarche by birth cohort: A pooled analysis of half a million women in Asia.

OBJECTIVES: To evaluate changes in the age at menarche in Asian populations. STUDY DESIGN: Retrospective cohort study. METHODS: We included 548,830 women from six countries in Asia. The data were sourced from 20 cohorts participating in the Asia Cohort Consortium (ACC) and two additional cohort studies: Japan Multi-institutional Collaborative Cohorts (J-MICC), and Japan Nurse Health Study (JNHS) with data on age at menarche. Joinpoint regression was used to evaluate changes in age at menarche by birth year and by country. RESULTS: The study includes data from cohorts in six Asian countries namely, China, Iran, Japan, Korea, Malaysia and Singapore. Birth cohorts ranged from 1873 to 1995. The mean age of menarche was 14.0 years with a standard deviation (SD) of 1.4 years, ranged from 12.6 to 15.5 years. Over 100 years age at menarche showed an overall decrease in all six countries. China showed a mixed pattern of decrease, increase, and subsequent decrease from 1926 to 1960. Iran and Malaysia experienced a sharp decline between about 1985 and 1990, with APC values of -4.48 and -1.24, respectively, while Japan, South Korea, and Singapore exhibited a nearly linear decline since the 1980s, notably with an APC of -3.41 in Singapore from 1993 to 1995. CONCLUSIONS: Overall, we observed a declining age at menarche, while the pace of the change differed by country. Additional long-term observation is needed to examine the contributing factors of differences in trend across Asian countries. The study could serve as a tool to strengthen global health campaigns.

Clinical impact of diastolic dysfunction and atrial fibrillation before and after initiating hemodialysis in patients with end-stage kidney disease.

BACKGROUND: Diastolic dysfunction with left ventricular hypertrophy and myocardial fibrosis is an important characteristic of uremic cardiomyopathy in end-stage kidney disease (ESKD). Few studies explored the relationship between changes in diastolic dysfunction and the risk of mortality or cardiovascular outcome in patients with ESKD. We investigated the clinical impact of diastolic dysfunction and atrial fibrillation (AF) on patients starting hemodialysis (HD). METHODS: A total of 718 patients who started HD between 2010 and 2020 were included. We classified patients according to the pre- and post-HD diastolic dysfunction grades (DDG) evaluated by echocardiography. Patients with AF were classified separately. The primary outcome was a composite outcome of all-cause mortality and cardiac complication. RESULTS: The median age was 63 years, and 61.4% were male. Patients were divided into four groups based on pre-HD echocardiography findings. After initiating HD, the patients were classified according to changes in DDG and AF. Composite outcomes were significantly higher in the pre-HD AF groups. However, after adjusting for age and history of ischemic heart disease, pre-HD AF did not affect the composite outcomes. Patients with normal post-HD diastolic function had better outcomes than those with diastolic dysfunction or AF. Furthermore, the deterioration of diastolic dysfunction after HD was associated with an increased risk of composite outcomes. CONCLUSIONS: The deterioration of diastolic dysfunction and newly development of AF after initiating HD were identified as risk factors for mortality and cardiac complications, supporting the clinical importance of the appropriate management of diastolic dysfunction and AF in patients with ESKD.

Fish and meat intake in relation to colorectal adenoma in asymptomatic Korean adults.

Introduction: Colorectal adenomas are recognized as precursors to colorectal cancer through the adenoma-carcinoma sequence. Identifying modifiable dietary factors that may inhibit cancer progression is critical, but epidemiologic studies in Asian populations are scarce. Methods: This study explored the impact of fish and meat intake on colorectal adenoma risk among Koreans. The study enrolled asymptomatic adults who visited Seoul National University Hospital Healthcare System Gangnam Center for health check-ups from May to December 2011. All participants underwent screening colonoscopy and completed a validated food frequency questionnaire. The study included 536 adenoma patients, 135 high-risk adenoma patients and 1,122 adenoma-free controls. Using multivariate logistic regression, we calculated odds ratios (ORs) and 95% confidence intervals (CIs) for fish and meat intake related to colorectal adenoma status, significant at p < 0.05. Results: The intake of total fish, meat, red meat, chicken or processed meat showed no clear association with the prevalence of colorectal adenoma after adjusting for age, education, smoking status, alcohol intake, physical activity, body mass index, metabolic syndrome, colorectal cancer family history, total energy intake, and total fruit and vegetable intake. However, higher fish intake was associated with lower odds of high-risk colorectal adenoma, with a significant trend observed across quartiles (P for trend = 0.04). This trend was more pronounced among men than women (P for trend = 0.01). Conclusion: In conclusion, we observed a significant inverse association between high fish intake and the prevalence of high-risk adenoma, but there were no clear associations between red and processed meat or chicken in the Korean population.

Safety and impact of the Mediterranean diet in patients with chronic kidney disease: a pilot randomized crossover trial.

Introduction: Emerging evidence highlights the potential advantages of the Mediterranean diet (MD) in preserving kidney function and slowing chronic kidney disease (CKD) progression. However, interventional studies on the MD are scarce in East Asian populations. Methods: This randomized crossover trial aimed to assess the safety and short-term impact of the Mediterranean Proper Optimal Balance (MEDi-POB) diet in Korean patients with stage 3-4 CKD. Kidney function was assessed using the estimated glomerular filtration rate, which was calculated using the CKD Epidemiology Collaboration equation. Fifty patients with CKD were randomly assigned to two groups, each starting with a different 4-week intervention, followed by a 4-week washout period, followed by a switch to the other 4-week intervention. During the MEDi-POB intervention, patients received home delivery of meals twice daily, 5 days a week, while the control intervention comprised a conventional diet. Forty-six patients successfully completed the entire 12-week trial. Paired t-tests were conducted to assess mean differences between the two groups. A linear mixed model was used to adjust for sequence and period. Results: Dietary fat, fiber, and niacin intake were significantly higher following the MEDi-POB diet than following the control diet (p = 0.001 for fat, p < 0.001 for fiber, and p = 0.007 for niacin). The MEDi-POB diet also yielded slightly increased total CO2 levels (p = 0.043), indicating effective management of metabolic acidosis. Conversely, sodium and copper intake were significantly lower with the MEDi-POB diet (p = 0.032 and p = 0.037, respectively). Caloric intake increased, but body mass index slightly decreased from baseline after consuming the MEDi-POB diet. Dietary potassium intake exhibited a non-significant increase (p = 0.053), and no significant changes in serum (p = 0.883) and urine potassium levels (p = 0.087) occurred. Kidney function remained well-preserved following the MEDi-POB diet. Conclusion: These results indicate that the MEDi-POB diet is safe even in patients with advanced CKD, as it does not adversely affect serum and urine potassium levels and helps maintain kidney function.

Endometrial E-cadherin and N-cadherin Expression during the Mid-Secretory Phase of Women with Ovarian Endometrioma or Uterine Fibroids.

BACKGROUND: Endometriosis and uterine fibroids are benign conditions frequently linked to subfertility/infertility. Recent research has highlighted the importance of epithelial-mesenchymal transition between embryonic and endometrial cells in the context of embryo implantation. Additionally, the adverse endometrial environment during implantation has been proposed as a mechanism contributing to infertility in endometriosis. Nevertheless, the role of cadherin molecule alterations in relation to endometrial receptivity and embryo invasion remains a subject of controversy. METHODS: We investigated the expression patterns of E-cadherin and N-cadherin in the endometria of women with ovarian endometrioma or uterine fibroids and assessed whether they differed from those of healthy women. We enrolled 17 women with ovarian endometrioma, 16 with uterine fibroids, and 6 healthy women. Endometrial tissues were obtained at the mid-secretory phase on days 19-24 of the menstrual cycle. The E-cadherin and N-cadherin mRNA and protein expression levels were measured using quantitative reverse transcriptase polymerase chain reaction and Western blot analysis, respectively. RESULTS: The E-cadherin and N-cadherin mRNA expression levels were higher and lower, respectively, in the endometrium of women with ovarian endometrioma than in those of the controls. In the endometrium of women with uterine fibroids, similar patterns with higher E-cadherin and lower N-cadherin levels were observed compared with that of the controls. Protein expression showed similar patterns. CONCLUSIONS: Our findings revealed higher E-cadherin expression and lower N-cadherin expression in the endometria of women with infertility-related diseases than in those of healthy women in the mid-secretory phase. This suggests a resistance to endometrial receptivity, potentially reflecting mesenchymal-epithelial transition properties.

Lifestyle Factors, Sociodemographic Characteristics and Incident Hypertension: A Prospective Analysis of the Korean National Health Insurance Service Sample Cohort.

BACKGROUND: Hypertension is a significant chronic disease globally, and lifestyle modifications are crucial for the prevention of this disease. We conducted a longitudinal analysis of the associations between lifestyle factors and the incidence of hypertension, stratified by sociodemographic characteristics. METHODS: We analyzed 113,022 adults (65,315 men), aged 20 years or older from the Korean National Health Insurance Service-National Sample Cohort 2.0 who participated in health screening between 2002 and 2003. Lifestyle factors (smoking, drinking, physical activity) were assessed at baseline using self reports, and incident hypertension was defined based on physician diagnoses. Cox proportional hazards regression models were used to assess associations. RESULTS: During an 11.6-year follow-up, 26,812 new cases of hypertension were identified. The risk of hypertension was high among men and women who smoked over 20 cigarettes daily (men: hazard ratio [HR]: 1.15; 95% confidence interval [CI], 1.08-1.21; women: HR: 1.62; 95% CI 1.17-2.25) and those who drank over 1.5 bottles of alcohol daily (men, HR: 1.18; 95% CI, 1.12-1.24; women, HR: 1.23; 95% CI 1.02-1.47). These associations tended to be high in high-income men (HR: 1.09; 95% CI, 1.04-1.14), low-income women (HR: 1.19; 95% CI, 1.05-1.35) and non-obese women (HR: 1.13; 95% CI, 1.01-1.27) who currently smoked. Physical activity was inversely associated with incident hypertension in men (HR: 0.96; 95% CI, 0.93-0.99). CONCLUSIONS: Unhealthy lifestyle factors, such as heavy smoking and drinking, was associated with an increased risk of hypertension, with variations by income, BMI, and sex. These findings underscore the importance of tailored, population-specific prevention strategies to address hypertension disparities.

Effect of intravenous methylprednisolone on serum antibody levels in thyroid eye disease.

BACKGROUND/AIMS: We evaluated longitudinal autoantibody changes after intravenous methylprednisolone (IVMP), compared them with those in untreated patients and identified prognostic factors for treatment response. METHODS: In this single-centre, retrospective, observational study, a total of 163 individuals diagnosed with moderate-to-severe thyroid eye disease were enrolled and followed for 12 months. Depending on whether IVMP was administered, we divided the patients into treatment and control groups. Based on the effect of IVMP on TSH receptor (TSH Rc) antibody level, we divided the patients into Ab declined and Ab not declined groups.We evaluated the time, group and interaction associations with the longitudinal autoantibody titres over 12 months using generalised estimating equations. Using multivariable logistic regression, we investigated the prognostic factors for a poor response to IVMP. RESULTS: In the IVMP group, the TSH Rc antibody (Ab) titre decreased rapidly for 6 months and then decreased slowly until 12 months, becoming similar to the control group at 12 months. This suggests a difference in the decreasing pattern over time between the IVMP and control groups (group and time interaction p=0.029). Total cholesterol (OR 1.0217 (95% CI 1.0068 to 1.0370), p=0.0043) was a significant prognostic factor for the steroid response. The threshold total cholesterol value to distinguish between Ab declined and Ab not declined was 186 mg/dL. CONCLUSION: IVMP significantly decreased the TSH Rc Ab level for the 3 months after treatment, compared with the no-treatment group, but the groups did not differ significantly after 12 months. Patients with high total cholesterol levels generally showed a poor response to IVMP.

Symptoms and Health-Related Quality of Life Among Older Adults Living With HIV.

BACKGROUND: As individuals living with HIV age, they often experience both physical and psychological symptoms-along with potential reductions in social support-which can significantly affect their health-related quality of life (HRQOL)-a crucial measure in HIV care. However, research exploring the potential predictive roles of social support and symptom experiences in HRQOL among older people living with HIV (PLWH) is limited. OBJECTIVES: This cross-sectional study aimed to investigate relationships between social support, symptom experiences, and HRQOL in older adults with HIV. METHODS: Older adults with HIV aged ≥50 years completed surveys on demographic and HIV-related characteristics, social support, four symptoms, and HRQOL. Hierarchical multiple linear regression analyses were used to determine predictors for six HRQOL domains. RESULTS: Among the 141 PLWH, significant associations were found between fatigue and health perceptions, physical functioning, and role functioning. Sleep disturbance was a significant predictor of health perceptions and social functioning. Anxiety displayed associations with physical functioning, role functioning, mental health, and pain. Depression was linked to health perceptions and mental health aspects of HRQOL. Notably, social support was not associated with any HRQOL domains. DISCUSSION: These findings underscore the importance of assessing a range of common symptoms to enhance HRQOL among older adults living with HIV, necessitating tailored symptom management strategies for this growing population.

Effect of Culture Temperature on 2-Methylisoborneol Production and Gene Expression in Two Strains of Pseudanabaena sp.

The presence of the odorant 2-methylisoborneol (2-MIB) in drinking water sources is undesirable. Although 2-MIB production is known to be influenced by temperature, its regulation at the gene level and its relationship with Chlorophyll-a (Chl-a) at different temperatures remain unclear. This study investigates the impact of temperature on 2-MIB production and related gene expression in Pseudanabaena strains PD34 and PD35 isolated from Lake Paldang, South Korea. The strains were cultured at three temperatures (15, 25, and 30 °C) to examine cell growth, 2-MIB production, and mic gene expression levels. 2-MIB production per cell increased with higher temperatures, whereas mic gene expression levels were higher at lower temperatures, indicating a complex regulatory mechanism involving post-transcriptional and enzyme kinetics factors. Additionally, the relationship between Chl-a and 2-MIB involved in metabolic competition was analyzed, suggesting that high temperatures appear to favor 2-MIB synthesis more than Chl-a synthesis. The distinct difference in the total amount of the two products and the proportion of 2-MIB between the two strains partially explains the variations in 2-MIB production. These findings highlight the significant effect of temperature on 2-MIB biosynthesis in Pseudanabaena and provide a valuable background for gene data-based approaches to manage issues regarding 2-MIB in aquatic environments.

Gastric and colorectal cancer incidence attributable to dietary factors in Korea.

Background: Dietary factors play a role in the etiology of gastrointestinal cancer. We aimed to estimate the burden of gastric and colorectal cancer that can be attributable to dietary factors in adults aged 20 years and older in Korea in 2018. Methods: Dietary intakes in 2000 were estimated using data from the 2001, 2005, and 2007-2018 Korea National Health and Nutrition Examination Survey (KNHANES). For counterfactual scenarios, the optimal level of intake suggested by the Global Burden of Disease (GBD) study was used if it was available. Otherwise, the average intake values of reference groups among published studies globally were used. Relative risks (RRs) were pooled through dose-response meta-analyses of Korean studies. Results: In Korea in 2018, an estimated 18.6% of gastric cancer cases and 34.9% of colorectal cancer cases were attributed to the combined effect of evaluated dietary factors. High intake of salted vegetables accounted for 16.0% of gastric cancer cases, followed by salted fish at 2.4%. Low intakes of whole grains (16.6%) and milk (13.7%) were leading contributors to colorectal cancer cases, followed by high intakes of processed meat (3.1%) and red meat (5.9%), and a low intake of dietary fiber (0.5%). Conclusions: These results suggest that a considerable proportion of gastric and colorectal cancer incidence might be preventable by healthy dietary habits in Korea. However, further research is needed to confirm the associations between dietary factors and gastric and colorectal cancers in Korea and to formulate and apply effective cancer prevention strategies to Koreans.

Improving Direct Yaw-Moment Control via Neural-Network-Based Non-Singular Fast Terminal Sliding Mode Control for Electric Vehicles.

Given the increased significance of electric vehicles in recent years, this study aimed to develop a novel form of direct yaw-moment control (DYC) to enhance the driving stability of four-wheel independent drive (4WID) electric vehicles. Specifically, this study developed an innovative non-singular fast terminal sliding mode control (NFTSMC) method that integrates NFTSM and a fast-reaching control law. Moreover, this study employed a radial basis function neural network (RBFNN) to approximate both the entire system model and uncertain components, thereby reducing the computational load associated with a complex system model and augmenting the overall control performance. Using the aforementioned factors, the optimal additional yaw moment to ensure the lateral stability of a vehicle is determined. To generate the additional yaw moment, we introduce a real-time optimal torque distribution method based on the vertical load ratio. The stability of the proposed approach is comprehensively verified using the Lyapunov theory. Lastly, the validity of the proposed DYC system is confirmed by simulation tests involving step and sinusoidal inputs conducted using Matlab/Simulink and CarSim software. Compared to conventional sliding mode control (SMC) and NFTSMC methods, the proposed approach showed improvements in yaw rate tracking accuracy for all scenarios, along with a significant reduction in the chattering phenomenon in control torques.

Prediction of post-donation renal function using machine learning techniques and conventional regression models in living kidney donors.

BACKGROUND: Accurate prediction of renal function following kidney donation and careful selection of living donors are essential for living-kidney donation programs. We aimed to develop a prediction model for post-donation renal function following living kidney donation using machine learning. METHODS: This retrospective cohort study was conducted with 823 living kidney donors between 2009 and 2020. The dataset was randomly split into training (80%) and test sets (20%). The main outcome was the post-donation estimated glomerular filtration rate (eGFR) 12 months after nephrectomy. We compared the performance of machine learning techniques, traditional regression models, and models from previous studies. The best-performing model was selected based on the mean absolute error (MAE) and root mean square error (RMSE). RESULTS: The mean age of the participants was 45.2 ± 12.3 years, and 48.4% were males. The mean pre-donation and post-donation eGFRs were 101.3 ± 13.0 and 68.8 ± 12.7 mL/min/1.73 m2, respectively. The XGBoost model with the eGFR, age, serum creatinine, 24-h urine creatinine, 24-h urine sodium, creatinine clearance, cystatin C, cystatin C-based eGFR, computed tomography volume of the remaining kidney/body weight, normalized GFR of the remaining kidney measured through a diethylenetriaminepentaacetic acid scan, and sex, showed the best performance with a mean absolute error of 6.23 and root mean square error of 8.06. An easy-to-use web application titled Kidney Donation with Nephrologic Intelligence (KDNI) was developed. CONCLUSIONS: The prediction model using XGBoost accurately predicted the post-donation eGFR after living kidney donation. This model can be applied in clinical practice using KDNI, the developed web application.

Eight-Year Prevalence Trends of Lumbar Spondylolysis and Isthmic Spondylolisthesis in Adolescent Males: A Population-Based Study from a Nationwide Military Draft Medical Examination Database in South Korea.

OBJECTIVE: To assess the national and regional trend in the prevalence of lumbar spondylolysis and isthmic spondylolisthesis for adolescent males in South Korea from 2015 to 2022. METHODS: A total of 2,666,277 Korean adolescent males were routinely examined at regional Military Manpower Administration offices. The data gathered from Military Manpower Administration were retrospectively collected to measure the prevalence and 95% confidence interval of lumbar spondylolysis and isthmic spondylolisthesis according to the year and region in South Korea. The Spearman correlation analysis was performed to assess the correlation between lumbar spondylolysis, isthmic spondylolisthesis, and several factors including height, weight, current smoking rate, and occasional and high-risk alcohol consumption. RESULTS: The prevalence of spondylolysis per 10,000 individuals showed a gradual increasing trend from 2015 to 2022 On the contrary, the prevalence of isthmic spondylolisthesis per 10,000 individuals decreased over a consecutive 8-year period. There were no statistical differences in the prevalence of spondylolysis and isthmic spondylolisthesis between Greater Seoul and the countryside. The prevalence of isthmic spondylolisthesis was significantly correlated with occasional (r=0.81, P=0.015) and high-risk alcohol consumption (r=0.86, P=0.007). CONCLUSIONS: The prevalence of lumbar spondylolysis among adolescent men has increased, whereas isthmic spondylolisthesis has shown a decline over a consecutive 8-year period. The trends in prevalence for both lumbar spondylosis and isthmic spondylolisthesis were similar across the regions in South Korea. Notably, there was a significant correlation between the prevalence of isthmic spondylolisthesis and the rate of alcohol consumption in adolescent men.

Migraine incidence and coffee consumption among child-bearing age women: the Korea Nurses' Health Study.

This longitudinal study aimed to identify factors that influence migraines in Korean women nurses using data from the Korea Nurses' Health Study. Among those who participated in Survey 1 (2013-2014) and the follow-up survey (2015-2019), we selected 2605 participants for Cox proportional hazard regression analysis, 521 participants who were newly diagnosed with migraine and 2084 controls using a 1:4 incidence density sampling approach. Consuming coffee (≥ 3 cups: RR = 1.666; 95% CI = 1.175-2.362, < 3 cups: RR = 1.439; 95% CI = 1.053-1.966), being obese (BMI ≥ 25: RR = 1.341, 95% CI = 1.003-1.793), and engaging in vigorous physical activity (RR = 1.010; 95% CI = 1.000-1.019) increased the risk of developing a migraine. Nurses with an annual salary greater than $3500 were less likely to develop migraines (RR = 0.786, 95% CI = 0.631-0.979). The results imply that lifestyle factors, such as the amount of coffee consumption, BMI level, and degree of physical activity could be considered when formulating treatment plans for women who have newly developed migraines.

Validation of prediction model for successful discontinuation of continuous renal replacement therapy: a multicenter cohort study.

BACKGROUND: Continuous renal replacement therapy (CRRT) has become the standard modality of renal replacement therapy (RRT) in critically ill patients. However, consensus is lacking regarding the criteria for discontinuing CRRT. Here we validated the usefulness of the prediction model for successful discontinuation of CRRT in a multicenter retrospective cohort. METHODS: One temporal cohort and four external cohorts included 1,517 patients with acute kidney injury who underwent CRRT for >2 days from 2018 to 2020. The model was composed of four variables: urine output, blood urea nitrogen, serum potassium, and mean arterial pressure. Successful discontinuation of CRRT was defined as the absence of an RRT requirement for 7 days thereafter. RESULTS: The area under the receiver operating characteristic curve (AUROC) was 0.74 (95% confidence interval, 0.71-0.76). The probabilities of successful discontinuation were approximately 17%, 35%, and 70% in the low-score, intermediate-score, and highscore groups, respectively. The model performance was good in four cohorts (AUROC, 0.73-0.75) but poor in one cohort (AUROC, 0.56). In one cohort with poor performance, attending physicians primarily controlled CRRT prescription and discontinuation, while in the other four cohorts, nephrologists determined all important steps in CRRT operation, including screening for CRRT discontinuation. CONCLUSION: The overall performance of our prediction model using four simple variables for successful discontinuation of CRRT was good, except for one cohort where nephrologists did not actively engage in CRRT operation. These results suggest the need for active engagement of nephrologists and protocolized management for CRRT discontinuation.

Free Fatty Acid 4 Receptor Activation Attenuates Collagen-Induced Arthritis by Rebalancing Th1/Th17 and Treg Cells.

Dietary supplementation with n-3 polyunsaturated fatty acids (PUFA) has been found to be beneficial in rodent rheumatoid arthritis models and human trials. However, the molecular targets of n-3 PUFAs and their beneficial effects on rheumatoid arthritis are under-researched. Free fatty acid receptor 4 (FFA4, also known as GPR120) is a receptor for n-3 PUFA. We aim to investigate whether FFA4 activation reduces collagen-induced rheumatoid arthritis (CIA) by using an FFA4 agonist, compound A (CpdA), in combination with DBA-1J Ffa4 gene wild-type (WT) and Ffa4 gene knock-out (KO) mice. CIA induced an increase in the arthritis score, foot edema, synovial hyperplasia, pannus formation, proteoglycan loss, cartilage damage, and bone erosion, whereas the administration of CpdA significantly suppressed those increases in Ffa4 WT mice but not Ffa4 gene KO mice. CIA increased mRNA expression levels of pro-inflammatory Th1/Th17 cytokines, whereas CpdA significantly suppressed those increases in Ffa4 WT mice but not Ffa4 gene KO mice. CIA induced an imbalance between Th1/Th17 and Treg cells, whereas CpdA rebalanced them in spleens from Ffa4 WT mice but not Ffa4 gene KO mice. In SW982 synovial cells, CpdA reduced the LPS-induced increase in pro-inflammatory cytokine levels. In summary, the present results suggest that the activation of FFA4 in immune and synovial cells could suppress the characteristics of rheumatoid arthritis and be an adjuvant therapy.

A novel allocation scheme for deceased donor kidneys to balance equity and utility.

Background: Patients with sensitization and blood type O experience increased waiting times for deceased-donor kidney transplantation (DDKT). While allocation benefits are needed to resolve inequity in DDKT opportunity, whether DDKT has comparable outcomes in this disadvantaged population requires further study. This study assessed these outcomes and developed a new allocation system that balances equity and utility. Methods: Patients from national and hospital cohorts from two centers in Korea were categorized as B1 to B4 (according to panel reactive antibody [PRA] positivity and ABO blood type) and A1 to A4 (based on the maximal PRA% and blood type), respectively. Competing risk and Cox regression analyses were performed to assess the effects of PRA and blood type on graft failure and mortality, respectively. Based on DDKT opportunities and posttransplant outcomes, a new scoring system for kidney allocation was developed. Results: The national and hospital cohorts included 3,311 and 819 patients, respectively, who underwent DDKT. Despite the disparities in DDKT opportunities, the graft failure rates and mortality did not differ among the different PRA and blood type groups. Furthermore, posttransplantation outcomes did not differ according to the categories with different DDKT opportunities. A new scoring system to provide additional points to disadvantaged populations was developed based on the hazard ratios for DDKT. Conclusion: A new allocation approach based on PRA and ABO blood types offers benefits to disadvantaged patients with fewer DDKT opportunities and could enhance equity without sacrificing utility in Korea, which has a long waiting time for DDKT.

Single-cell analysis reveals cellular and molecular factors counteracting HPV-positive oropharyngeal cancer immunotherapy outcomes.

BACKGROUND: Oropharyngeal squamous cell carcinoma (OPSCC) induced by human papillomavirus (HPV-positive) is associated with better clinical outcomes than HPV-negative OPSCC. However, the clinical benefits of immunotherapy in patients with HPV-positive OPSCC remain unclear. METHODS: To identify the cellular and molecular factors that limited the benefits associated with HPV in OPSCC immunotherapy, we performed single-cell RNA (n=20) and T-cell receptor sequencing (n=10) analyses of tonsil or base of tongue tumor biopsies prior to immunotherapy. Primary findings from our single-cell analysis were confirmed through immunofluorescence experiments, and secondary validation analysis were performed via publicly available transcriptomics data sets. RESULTS: We found significantly higher transcriptional diversity of malignant cells among non-responders to immunotherapy, regardless of HPV infection status. We also observed a significantly larger proportion of CD4+ follicular helper T cells (Tfh) in HPV-positive tumors, potentially due to enhanced Tfh differentiation. Most importantly, CD8+ resident memory T cells (Trm) with elevated KLRB1 (encoding CD161) expression showed an association with dampened antitumor activity in patients with HPV-positive OPSCC, which may explain their heterogeneous clinical outcomes. Notably, all HPV-positive patients, whose Trm presented elevated KLRB1 levels, showed low expression of CLEC2D (encoding the CD161 ligand) in B cells, which may reduce tertiary lymphoid structure activity. Immunofluorescence of HPV-positive tumors treated with immune checkpoint blockade showed an inverse correlation between the density of CD161+ Trm and changes in tumor size. CONCLUSIONS: We found that CD161+ Trm counteracts clinical benefits associated with HPV in OPSCC immunotherapy. This suggests that targeted inhibition of CD161 in Trm could enhance the efficacy of immunotherapy in HPV-positive oropharyngeal cancers. TRIAL REGISTRATION NUMBER: NCT03737968.