Adaptive Nutrition Intervention Stabilizes Serum Phosphorus Levels in Hemodialysis Patients: A Multicenter Decentralized Clinical Trial Using Real-World Data.

OBJECTIVE: This study aims to evaluate the effect of an adaptive nutritional and educational intervention for patients on hemodialysis (HD) in a routine care setting, using real-world data from electronic health records. METHODS: Decentralized clinical trial of seven HD facilities recruited patients who have been on HD for over 3 months (N = 153) for an 8-week adaptive intervention protocol. Patients were divided into four groups: (1) control (2) education intervention (3) meal intervention (4) education and meal interventions. Educational contents were digitally delivered via mobile phones and premade meals tailored on laboratory findings were home-delivered. Changes in serum electrolytes and malnutrition inflammation score (MIS) were analyzed. RESULTS: Meal intervention statistically significantly stabilized serum phosphorus level (ß = -0.81 mg/dL, 95% confidence interval = [-1.40, -0.22]) at week 8, with increased likelihood of being within target serum value range (odds ratio = 1.21, 95% confidence interval = [1.04, 1.40]). Meal group showed better nutritional status (MIS = 3.65) than the education group (MIS = 5.10) at week 8 (adjusted p < .05). No significant changes were observed in serum potassium level, depression, and self-efficacy. CONCLUSION: It was demonstrated that an adaptive meal intervention in a real-world care setting may benefit serum phosphorus control and nutritional status of patients on HD, without negative effect on depression levels or self-efficacy. More work is needed to develop an effective educational intervention.

Nurse Caseload and Patient Survival in Hemodialysis Units: A Korean Nationwide Cohort Study.

INTRODUCTION: The patient-to-nurse ratio is highly variable among dialysis facilities. However, there is little known about the association between nurse caseload and hemodialysis (HD) patient outcomes. We evaluated the association between patient-to-nurse ratio and mortality in the Korean patients undergoing HD. METHODS: We used HD quality assessment data and National Health Insurance Service claim data from the year of 2013 for collecting demographic and clinical data. Altogether, 21,817 patients who participated in the HD quality assessment in 2013 were included in the study. Nurse caseload was defined as the number of HD sessions performed by a nurse per working day. The patients were divided into two groups according to the nurse caseload as follows: low nurse caseload group (≤6.0) and high nurse caseload group (>6.0). We analyzed mortality risk based on nurse caseload using the Cox proportional hazard model. RESULTS: The mean age was 59.1 years, and males accounted for 58.5%. The mean hemoglobin was 10.6 g/dL and albumin was 3.99 g/dL. At the mean follow-up duration of 51.7 (20.6) months, the ratio between low and high groups was 69.6% (15,184 patients) versus 30.4% (6,633 patients). The patients in the high nurse caseload group were older and showed lower levels of hemoglobin, albumin, calcium, and iron saturation and higher levels of phosphorus than those in the low nurse caseload group. A high nurse caseload was associated with a lower survival rate. In the adjusted Cox analysis, a high nurse caseload was an independent risk factor for all-cause mortality (hazard ratio 1.08; 95% confidence interval, 1.02-1.14; p = 0.01). CONCLUSION: High nurse caseload was associated with an increased mortality risk among the patients undergoing HD. Further prospective studies are needed to determine whether a caseload of nursing staff can improve the prognosis of HD patients.

Relationship Between Arteriovenous Fistula Stenosis and Circulating Levels of Neutrophil Granule Proteins in Chronic Hemodialysis Patients.

BACKGROUND: Arteriovenous fistula (AVF) stenosis leading to its failure is a major cause of morbidity in hemodialysis patients; however, detailed pathogenesis of AVF stenosis is still under investigation. To date, monocytes/macrophages have been considered pivotal players in chronic inflammation of vascular disease including atherosclerosis and AVF stenosis. However, recent evidence strongly suggests that neutrophils and neutrophil granule proteins are important contributors to vascular disease. The aim of the present study was to evaluate the relationship between AVF stenosis and neutrophil activation by measuring circulating levels of neutrophil elastase (NE) and lactoferrin, enzymes released on neutrophil activation, as well as other inflammation markers including neutrophil counts. METHODS: This was a single-center, prospective observational study conducted on 83 prevalent hemodialysis patients with AVF. Blood levels of biomarkers and sonography (US) measurement were assessed at baseline and 1 year after enrollment. Clinical follow-up continued for one more year (a total of 2 years for each patient) to observe any AVF events. RESULTS: Circulating levels of both NE and lactoferrin positively correlated with the degree of AVF stenosis. Patients with significant AVF stenosis had older AVFs, higher neutrophil-to-lymphocyte ratio (NLR), and higher circulating levels of NE and lactoferrin. On multivariate logistic regression analysis, both circulating levels of NE and NLR remained independent predictors of significant AVF stenosis. CONCLUSIONS: Circulating levels of NE and the NLR were identified as independent predictors of at-risk AVF with significant stenosis. Our data suggest the potential role of neutrophil and innate immunity activation on the development of AVF stenosis.

Characteristics of bioimpedance-determined fluid shifts according to intradialytic blood pressure difference.

This study was designed to identify the fluid spaces that are most changed during ultrafiltration (UF) according to intradialytic blood pressure (BP) difference. BP data were collected five times (before hemodialysis [HD] and 1-4 h of HD). Intradialytic BP difference was calculated as the highest minus lowest of these BP measurements. Intradialytic systolic BP (SBP) difference over 20 mm Hg and diastolic BP (DBP) difference over 10 mm Hg were defined as wide intradialytic SBP difference (SYS-W) and DBP difference (DIA-W), respectively. We measured the various fluid spaces before HD and 1-4 h of HD, and 30 min after HD using a portable, whole-body bioimpedance spectroscopy (BIS). In this study, 85 prevalent patients aged over 18 years with a fixed dry weight (65.38 ± 12.45 years, 54.18% men, 52.50% patients with diabetes), undergoing HD had participated. 1) Mean relative reduction of extracellular water (ECW) was significantly higher in SYS-W than in narrow intradialytic SBP difference (SYS-N) patients from 1 h to 30 min after HD. 2) Mean relative reduction of intracellular water (ICW) was significantly lower in DIA-W than in narrow intradialytic DBP difference (DIA-N) patients from 1 h to 30 min after HD. 3) ECW of patients with SYS-W was significantly lower than that of patients with SYS-N. Patients with SYS-W have the characteristics of fluid shifts in which reduction of ECW was steeper than patients with SYS-N whereas fluid shifts of ICW were lower in patients with DIA-W than patients with DIA-N.

Health Insurance Status Is Related to Risk of Mortality and Hospitalization in Korean Maintenance Hemodialysis Patients: A Longitudinal Cohort Study.

BACKGROUND: There has been an increasing incidence of hemodialysis (HD) due to old age and comorbid condition such as diabetes. In general, socioeconomic status (SES) is known as one of the most important risk factors for patient mortality and morbidity. Whether low SES is associated with poorer outcome in HD patients is controversial. This study was performed to evaluate the association of health insurance status as a proxy indicator for SES upon mortality and hospitalization in maintenance HD patients. METHODS: We used HD-quality assessment data from the year of 2015 for collecting demographic and clinical data. The subjects were classified into Medical Aid (MA) recipients (low SES) and National Health Insurance (NHI) beneficiary (high SES). We analyzed mortality and hospitalization risk based on health insurance status using Cox proportional hazard model. A total of 35,454 adult HD patients ≥18 years old who received HD treatment more than twice weekly were included in the analysis. RESULTS: The ratio between MA recipient and NHI beneficiary was 76.7 versus 23.3%. The MA recipient group demonstrated younger age and lower proportion of female, diabetes, hypertension, and cerebrovascular accidents compared to the NHI beneficiary group. After adjusting for age, gender, comorbidity, and laboratory parameters, the MA recipient group showed a significantly higher mortality risk compared to the NHI beneficiary group (hazard ratio 1.073 [1.009-1.14], p = 0.025). The MA recipient group was also an independent risk factor for hospitalization after adjusting for age, gender, comorbidities, and laboratory parameters (hazard ratio 1.142 [1.108-1.178], p < 0.001). CONCLUSION: Low SES as measured by health insurance status was associated with an increased risk of patient mortality and hospitalization in Korean maintenance HD patients.

Changes in FGF-23, Neutrophil/Platelet Activation Markers, and Angiogenin in Advanced Chronic Kidney Disease and Their Effect on Arterial Stiffness.

AIMS: The aims of this study were to measure changes in fibroblast growth factor 23 (FGF-23), neutrophil (elastase, lactoferrin)/platelet activation marker (mean platelet volume-to-platelet count ratio [MPR]), and angiogenin according to the stage of chronic kidney disease (CKD), and to evaluate the association of FGF-23, elastase, lactoferrin, MPR, and angiogenin with arterial stiffness using brachial-ankle pulse wave velocity (ba-PWV) in CKD patients. METHODS: According to the estimated glomerular filtration rate (eGFR) calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation, the patients were allocated to five groups: (1) normal controls (eGFR ≥90 mL/min/1.73 m2 without pathologic, urine [proteinuria], blood [electrolyte], and imaging abnormalities; n = 22); (2) CKD stage 2 (eGFR 60-89 mL/min/1.73 m2; n = 17); (3) CKD stage 3 (eGFR 30-59 mL/min/1.73 m2; n = 22); (4) CKD stage 4 (eGFR 15-30 mL/min/1.73 m2; n = 17); and (5) CKD stage 5-hemodialysis (HD) (n = 30). All the patients were free of clinically apparent cardiovascular disease. Serum FGF-23, elastase, lactoferrin, and angiogenin concentrations and the MPR were measured to study the association of the above parameters with the clinical (age, sex, presence of diabetes mellitus, and blood pressure), biochemical (calcium, phosphorus, uric acid, intact parathyroid hormone [PTH], low-density lipoprotein cholesterol, and high-sensitivity C-reactive protein), and ba-PWV values of the CKD patients. RESULTS: (1) The mean ba-PWV values were 1,497.2 ± 206.4 cm/s in the controls, 1,649.0 ± 247.9 cm/s in the CKD stage 2 group (p < 0.05 vs. controls), 1,655.8 ± 260.3 cm/s in the CKD stage 3 group (p < 0.05 vs. controls), 1,823.0 ± 402.4 cm/s in the CKD stage 4 group (p < 0.05 vs. controls and CKD stages 2 and 3), and 1,905.2 ± 374.1 cm/s in the CKD stage 5-HD group (p < 0.05 vs. controls and CKD stage 2). (2) The mean log10(FGF-23) concentration values were 0.77 ± 0.27, 0.97 ± 0.48, 1.10 ± 0.35 (p < 0.05 vs. controls and CKD stage 2), 1.35 ± 0.48 (p < 0.05 vs. controls and CKD stages 2 and 3), and 2.12 ± 0.82 (p < 0.05 vs. controls and CKD stages 2-4); the mean angiogenin levels were 230.6 ± 70.5 pg/mL, 283.0 ± 53.5 pg/mL (p < 0.05 vs. controls), 347.3 ± 76.9 pg/mL (p < 0.05 vs. controls and CKD stage 2), 445.9 ± 90.6 pg/mL (p < 0.05 vs. controls and CKD stages 2 and 3), and 370.9 ± 142.4 pg/mL (p < 0.05 vs. controls and CKD stages 2 and 3). (3) In the stage 3-4 CKD/HD patients, the mean elastase-to-neutrophil and lactoferrin-to-neutrophil ratios were significantly lower than in the controls and the stage 2 CKD patients. (4) Our multivariate linear regression analyses showed that age, pulse pressure, mean arterial pressure, PTH, and FGF-23 were independently associated with ba-PWV values. CONCLUSIONS: Circulating FGF-23 and angiogenin concentrations gradually increased as CKD advanced, whereas neutrophil activation markers were significantly lower in the stage 3-4 CKD/HD patients than in the controls and stage 2 CKD patients. FGF-23 was weakly associated with ba-PWV values in patients with CKD/HD and no previous cardiovascular disease.

Delta neutrophil index is an independent predictor of mortality in septic acute kidney injury patients treated with continuous renal replacement therapy.

BACKGROUND: Delta neutrophil index (DNI), representing an elevated fraction of circulating immature granulocytes in acute infection, has been reported as a useful marker for predicting mortality in patients with sepsis. The aim of this study was to evaluate the prognostic value of DNI in predicting mortality in septic acute kidney injury (S-AKI) patients treated with continuous renal replacement therapy (CRRT). METHOD: This is a retrospective analysis of consecutively CRRT treated patients. We enrolled 286 S-AKI patients who underwent CRRT and divided them into three groups based on the tertiles of DNI at CRRT initiation (high, DNI > 12.0%; intermediate, 3.6-12.0%; low, < 3.6%). Patient survival was estimated with the Kaplan-Meier method and Cox proportional hazards models to determine the effect of DNI on the mortality of S-AKI patients. RESULTS: Patients in the highest tertile of DNI showed higher Acute Physiology and Chronic Health Evaluation II score (highest tertile, 27.9 ± 7.0; lowest tertile, 24.6 ± 8.3; P = 0.003) and Sequential Organ Failure Assessment score (highest tertile, 14.1 ± 3.0; lowest tertile, 12.1 ± 4.0; P = 0.001). The 28-day mortality rate was significantly higher in the highest tertile group than in the lower two tertile groups (P < 0.001). In the multiple Cox proportional hazard model, DNI was an independent predictor for mortality after adjusting multiple confounding factors (hazard ratio, 1.010; 95% confidence interval, 1.001-1.019; P = 0.036). CONCLUSION: This study suggests that DNI is independently associated with mortality of S-AKI patients on CRRT.

Normal body mass index with central obesity has increased risk of coronary artery calcification in Korean patients with chronic kidney disease.

In chronic kidney disease (CKD), overweight and mild obesity have shown the lowest cardiovascular (CV) risk. However, central obesity has been directly associated with CV risk in these patients. This bidirectional relationship of body mass index (BMI) and central obesity prompted us to evaluate CV risk based on a combination of BMI and waist-to-hip ratio (WHR) in nondialysis CKD patients. We included 1078 patients with CKD stage 2 through 5 (nondialysis) enrolled in a nationwide prospective cohort of Korea. Patients were divided into 3 groups by BMI (normal BMI, 18.5-22.9; overweight, 23.0-27.4; and obese, 27.5 and over kg/m2) and were dichotomized by a sex-specific median WHR (0.92 in males and 0.88 in females). Coronary artery calcification (CAC) was determined by multislice computed tomography. CAC (score above 10 Agatston units) was found in 477 patients. Multivariate logistic regression analysis indicated that BMI was not independently associated with CAC. However, WHR showed an independent linear and significant association with CAC (odds ratio, 1.036; 95% confidence interval, 1.007-1.065 per 0.01 increase). Furthermore, when patients were categorized into 6 groups according to a combination of BMI and WHR, normal BMI but higher WHR had the highest risk of CAC compared with the normal BMI with lower WHR group (2.104; 1.074-4.121). Thus, a normal BMI with central obesity was associated with the highest risk of CAC, suggesting that considering BMI and WHR, 2 surrogates of obesity, can help to discriminate CV risk in Korean nondialysis CKD patients.

Glomerular IgG deposition predicts renal outcome in patients with IgA nephropathy.

Glomerular IgG deposition is frequently observed in patients with IgA nephropathy. However, the association between glomerular IgG deposition and progression of IgA nephropathy is uncertain. Six hundred and twenty-seven patients with biopsy-proven IgA nephropathy were recruited. Histological variables of the Oxford classification (Oxford-MEST) and the presence of glomerular IgG deposits were assessed. Renal progression defined as end-stage renal disease or 50% reduction in estimated glomerular filtration rate was analyzed using Kaplan-Meier methods and Cox regression analysis. Of the study population, 200 patients (31.9%) had glomerular IgG deposition on immunofluorescence staining. During a mean follow-up of 56.8±37.5 months, the rate of renal progression was significantly higher in the IgA nephropathy patients with glomerular IgG deposition compared with the IgA nephropathy patients without glomerular IgG deposition (39.8 vs 12.3 per 1000 patient-years; P<0.001). Of patients with IgG deposition, 178 (28.3%), 20 (3.2%), and 2 (0.3%) patients had mild, moderate, and marked glomerular IgG deposits, receptively. Kaplan-Meier analysis revealed that cumulative renal survival was significantly lower in IgA nephropathy patients with the higher intensity of glomerular IgG deposits (P<0.001). In addition, Cox regression analysis revealed that moderate and marked glomerular IgG deposits significantly predicted renal outcome independent of Oxford-MEST and clinical variables (HR, 2.97; 95% CI, 1.01-8.77; P=0.04). This study showed that that glomerular IgG deposition was independently associated with poor renal outcome in patient with IgA nephropathy.

Identification of candidate domestication regions in the radish genome based on high-depth resequencing analysis of 17 genotypes.

KEY MESSAGE: This study provides high-quality variation data of diverse radish genotypes. Genome-wide SNP comparison along with RNA-seq analysis identified candidate genes related to domestication that have potential as trait-related markers for genetics and breeding of radish. Radish (Raphanus sativus L.) is an annual root vegetable crop that also encompasses diverse wild species. Radish has a long history of domestication, but the origins and selective sweep of cultivated radishes remain controversial. Here, we present comprehensive whole-genome resequencing analysis of radish to explore genomic variation between the radish genotypes and to identify genetic bottlenecks due to domestication in Asian cultivars. High-depth resequencing and multi-sample genotyping analysis of ten cultivated and seven wild accessions obtained 4.0 million high-quality homozygous single-nucleotide polymorphisms (SNPs)/insertions or deletions. Variation analysis revealed that Asian cultivated radish types are closely related to wild Asian accessions, but are distinct from European/American cultivated radishes, supporting the notion that Asian cultivars were domesticated from wild Asian genotypes. SNP comparison between Asian genotypes identified 153 candidate domestication regions (CDRs) containing 512 genes. Network analysis of the genes in CDRs functioning in plant signaling pathways and biochemical processes identified group of genes related to root architecture, cell wall, sugar metabolism, and glucosinolate biosynthesis. Expression profiling of the genes during root development suggested that domestication-related selective advantages included a main taproot with few branched lateral roots, reduced cell wall rigidity and favorable taste. Overall, this study provides evolutionary insights into domestication-related genetic selection in radish as well as identification of gene candidates with the potential to act as trait-related markers for background selection of elite lines in molecular breeding.

Serum Ferritin Predicts Mortality Regardless of Inflammatory and Nutritional Status in Patients Starting Dialysis: A Prospective Cohort Study.

BACKGROUND: The impact of serum ferritin on prognosis in patients starting hemodialysis (HD) is not fully elucidated. METHODS: A prospective cohort of 946 incident HD patients from 26 dialysis centers in Korea was selected for this study. Patients were divided into tertiles according to natural logarithm (Ln) ferritin concentrations. RESULTS: During a median follow-up of 39 months, 88 (9.3%) patients died. Multivariate Cox proportional hazard analysis demonstrated that Ln ferritin was independently associated with an increase in cardiovascular mortality risk (hazard ratio (HR) 1.604, 95% CI 1.040-2.474, p = 0.033), infection-related mortality risk (HR 1.916, 95% CI 1.056-3.476, p = 0.032), and all-cause mortality risk (HR 1.547, 95% CI 1.156-2.069, p = 0.003). CONCLUSION: Serum ferritin levels at the time of HD commencement were a significant independent risk factor for mortality regardless of systemic inflammation and nutritional status. Therefore, elevated serum ferritin levels could be an effective indicator for prognosis.

Association between the emotional status of family caregivers and length of stay in a palliative care unit: A retrospective study.

OBJECTIVE: Several factors associated with referral time to hospice and/or palliative care services have been identified, but there is no literature on the association between these services and the emotional status of the family caregivers (FCs). This article is intended to address that issue. METHOD: A semistructured interview was employed to collect data for a retrospective cohort study. The primary FCs of terminally ill cancer patients were interviewed at the time of the patient's referral to the palliative care unit. Interview data were combined with patients' medical record data for our analysis. The emotional status of the FCs was categorized into one of three groups according to their responses to the anticipated death of their family member: acceptance, anxious/depressed, and denial/angry. A Cox proportional hazard model was used to examine and identify the factors related to the length of stay (LOS) in the palliative care unit. RESULTS: A total of 198 patient-FC pairs were identified. The median LOS was 18 days. A multivariate analysis with adjustment for potential variables revealed significant differences in LOS according to cancer type and time since cancer diagnosis. The denial/angry FC category was independently associated with a shorter LOS (vs. acceptance, adjusted hazard ratio (aHR) 2.11; 95% confidence interval (CI), 1.11-4.03). SIGNIFICANCE OF RESULTS: We found that terminally ill cancer patients who were referred late had FCs who were in denial or were angry about the anticipated death of their loved one. The emotional status of FCs should be considered when patients with terminal cancer are referred to palliative care.

Using the Oxford classification of IgA nephropathy to predict long-term outcomes of Henoch-Schönlein purpura nephritis in adults.

Recently, there has been emerging concern that crescents, the main histologic feature of Henoch-Schönlein purpura nephritis, merely reflect active inflammation, and may not be useful in predicting long-term outcomes. We therefore conducted a single-center retrospective study to evaluate whether the new Oxford classification of immunoglobulin A nephropathy can be used to predict long-term outcome in patients with Henoch-Schönlein purpura nephritis. We included 61 biopsy-proven patients with Henoch-Schönlein purpura nephritis between January 1991 and August 2010. In addition to the International Study of Kidney Disease in Children classification, pathologic findings were also evaluated by the Oxford classification. Primary outcomes were defined as either the onset of estimated glomerular filtration rate <60 ml/min per 1.73 m(2) with ≥30% decrease in estimated glomerular filtration rate from baseline or end-stage renal disease. During a median follow-up of 49.3 months, 13 (21%) patients reached the primary end point. A Kaplan-Meier plot showed that renal event-free survival was significantly longer in patients with <50% crescents than in those with crescents in ≥50% of glomeruli (P=0.003). Among the components of the Oxford classification, patients with endocapillary hypercellularity (E1; P=0.016) and tubular atrophy/interstitial fibrosis (T1/T2; P=0.018) had lower renal survival rates than those with E0 and T0. In a multivariate Cox model adjusted for clinical and pathologic factors, E1 (hazard ratio=8.91; 95% confidence interval=1.47-53.88; P=0.017) and T1/T2 (hazard ratio=8.74; 95% confidence interval=1.40-54.38; P=0.020) were independently associated with reaching a primary outcome, whereas the extent of crescentic lesions was not. Our findings suggest that the Oxford classification can be used in predicting long-term outcomes of Henoch-Schönlein purpura nephritis.

LDL cholesterol affects clinical outcomes in incident hemodialysis patients during the early stages of dialysis.

BACKGROUND/AIMS: Using a cohort of incident hemodialysis (HD) patients, this study investigated the impact of lipid profiles on clinical outcomes, especially in the early period of dialysis. METHODS: A prospective cohort of 867 incident HD patients was selected. In order to determine the impact of cholesterol level on primary outcome, Cox regression analyses were performed for LDL and non-HDL (NHDL) variables. RESULTS: Univariate analysis revealed an increase in primary outcome risk with an LDL cholesterol level of 100 mg/dl or higher compared to an LDL cholesterol level lower than 100 mg/dl. High LDL cholesterol remained a significant independent predictor of the composite outcome, even after adjusting for age, gender, diabetes mellitus, preexisting CV disease, albumin, and hs-CRP. CONCLUSION: Serum LDL cholesterol at the time of HD commencement was a significant independent risk factor for the composite outcome of all-cause mortality and CV events in incident HD patients during the early stages of dialysis.

Clinical features and outcomes of focal segmental glomerulosclerosis pathologic variants in Korean adult patients.

BACKGROUND: Many studies have shown that clinical characteristics and outcomes differ depending on pathologic variants of focal segmental glomerulosclerosis (FSGS). However, these are not well defined in Asian populations. METHODS: This retrospective study evaluated clinical features and outcomes of pathologic FSGS variants in 111 adult patients between January 2004 and December 2012. Primary outcome was the composite of doubling of baseline serum creatinine concentrations (D-SCr) or onset of end-stage renal disease (ESRD). Secondary outcome included complete (CR) or partial remission (PR). RESULTS: There were 70 (63.1%), 20 (18.0%), 17 (15.3%), 3 (2.7%), and 1 (0.9%) patients with not-otherwise specified (NOS), tip, perihilar, cellular, and collapsing variants, respectively. At presentation, nephrotic-range proteinuria occurred more commonly in tip lesion than in other variants. The overall 5-year renal survival rate was 76.8%. During a median follow-up of 34.5 months, only 1 (5.0%) patient with a tip lesion reached the composite end point compared to 2 (11.8%) and 12 (17.1%) patients in perihilar and NOS variants, but this difference was not statistically significant in an adjusted Cox model. However, tip lesion was associated with a significantly increased probability of achieving CR (P = 0.044). CONCLUSION: Similar to other populations, Korean adult patients with FSGS have distinct clinical features with the exception of a rare frequency of cellular and collapsing variants. Although pathologic variants were not associated with overall outcome, the tip variant exhibited favorable outcome in terms of achieving remission. Further studies are required to delineate long-term outcome and response to treatment of the pathologic variants.

CHFR is negatively regulated by SUMOylation-mediated ubiquitylation.

CHFR ubiquitin ligase plays an important role in cell cycle progression and tumorigenesis. CHFR tumor suppressor function is highly associated with its protein level. We recently reported that CHFR protein levels are negatively regulated by SUMOylation-mediated proteasomal degradation. In the present study, we uncover a detailed molecular mechanism how SUMOylation promotes CHFR destabilization. We demonstrate that SUMO modification of CHFR promotes its ubiquitylation and subsequent proteasomal degradation. However, SUMOylation of CHFR does not affect its auto-ubiquitylation, which generally serves as a maintenance mechanism for most ubiquitin ligases. Moreover, the E3 ubiquitin ligase activity of CHFR is dispensable for this SUMOylation-mediated ubiquitylation and degradation. Conversely, SENP2 deSUMOylating enzyme reduces SUMOylation-induced ubiquitylation of CHFR, leading to elevated CHFR protein levels. Taken together, our results present a new regulatory mechanism for CHFR that sequential post-translational modifications of CHFR by SUMO and ubiquitin coordinately regulates its stability.

SUMOylation negatively regulates the stability of CHFR tumor suppressor.

CHFR ubiquitin ligase acts as a checkpoint upon DNA damage and its functional inactivation is one of key characteristics of tumor development and metastasis. Despite the crucial role in maintaining genome integrity and cell cycle progression, little is known how CHFR stability is regulated. Here, we showed that CHFR is covalently modified by SUMO-1 at lysine 663 and subsequently destabilized by ubiquitin-proteasome system. While CHFR(K663R) substitution mutation does not alter its subcellular localization, SUMOylation-defective CHFR(K663R)-stable cells exhibit substantial growth suppression due to the increased stability of CHFR(K663R). Moreover, protein level of CHFR, not CHFR(K663R), is rapidly declined under SUMOylation-promoting conditions, and SENP2 deSUMOylating enzyme reverses its SUMO-modification. Collectively, we demonstrated that CHFR stability is regulated by SUMOylation-dependent proteasomal degradation. Therefore, our study underscores the importance of CHFR SUMOylation as a new regulatory mechanism of CHFR and highlights the emerging role of SUMOylation in modulating protein stability.

Ancient schwannoma in the parotid gland: A case report and review of the literature.

Schwannomas are uncommon neoplasms of neurologic origin that are rare in the salivary glands. A schwannoma that persists for a long time is referred to as an ancient schwannoma if it is accompanied by degenerative changes on histology. The case described herein involved a 37-year-old man with an ancient schwannoma that had persisted for 20 years in his right parotid gland. Clinically, the lesion presented with swelling and pain. Computed tomography revealed a well-defined, multilocular enhanced lesion. T2-weighted magnetic resonance images displayed multilocular hyperintensity, while T1-weighted images showed a high signal at the lobulated margin and a homogeneous low signal internally. The preoperative diagnosis, based on the lesion's location and imaging diagnosis, was Warthin's tumor. However, a biopsy conducted after surgical excision identified the lesion as a schwannoma with cystic degeneration. This report also presents a summary of the characteristics of rare cases of schwannoma in the major salivary gland based on this case and a literature review.

Impact of sarcopenia and phase angle on mortality of the very elderly.

BACKGROUND: Sarcopenia is a major component of geriatric syndrome and associated with poor clinical outcomes and mortality. However, diagnosing sarcopenia in the very elderly is difficult, and data on its epidemiology and devastating effects in this group are scarce. Phase angle (PA) is measured using bioimpedance spectroscopy and known to reflect cellular integrity and health. This study aimed to clarify the impact of sarcopenia and PA on mortality risk in very elderly people living in long-term care facilities. METHODS: This prospective cohort study enrolled elderly residents living in nine long-term care facilities. We collected the participants' data, such as body mass index (BMI), comorbidities and laboratory data, from September to October 2017 and mortality data until October 2019. Nutritional status was evaluated using the Mini Nutritional Assessment (MNA) score, and multifrequency bioimpedance spectroscopy was used to assess body composition including PA. Appendicular skeletal muscle mass was calculated using the body composition monitor-derived equation of Taiwan's researchers. Sarcopenia was diagnosed using the European Working Group on Sarcopenia in Older People 2 (EWGSOP2) definition (sarcopenia vs. normal group). We divided the participants into two groups according to the median PA value of 3.65° (high vs. low group) and performed multivariate regression analyses to verify the association with mortality risk according to sarcopenia diagnosis or PA group. RESULTS: A total of 279 elderly participants were enrolled; of them, 238 (85.3%) were diagnosed with sarcopenia according to EWGSOP2 guidelines. The median patient age was 83 years, 211 (75.6%) were female and the median BMI was 20.4 kg/m2 . The sarcopenia group was older than the normal group (84 vs. 81 years; P = 0.002), had a lower mean BMI (19.8 vs. 26.6 kg/m2 , P < 0.001) and had a lower MNA score (9 vs. 12 points, P < 0.001). Sarcopenia was associated with a higher mortality risk after the adjustment for age, sex and diabetes mellitus (hazard ratio [HR], 3.744; 95% confidence interval [CI], 1.155-12.134; P = 0.028). A low PA was associated with sarcopenia, older age, female sex, low MNA score and overhydration volume; it was also a significant predictor of mortality after the adjustment for age, sex, diabetes mellitus and MNA score (HR, 0.593; 95% CI, 0.420-0.837; P = 0.003). CONCLUSIONS: Sarcopenia is prevalent among the very elderly patients in long-term care facilities. Sarcopenia and low PA are significantly associated with higher mortality risk.