Glomerular crescents are associated with the risk of type 2 diabetic kidney disease progression: a retrospective cohort study.

BACKGROUND: Diabetic kidney disease (DKD) stands as the predominant cause of chronic kidney disease and end-stage kidney disease. Its diverse range of manifestations complicates the treatment approach for patients. Although kidney biopsy is considered the gold standard for diagnosis, it lacks precision in predicting the progression of kidney dysfunction. Herein, we addressed whether the presence of glomerular crescents is linked to the outcomes in patients with biopsy-confirmed type 2 DKD. METHODS: We performed a retrospective evaluation, involving 327 patients diagnosed with biopsy-confirmed DKD in the context of type 2 diabetes, excluding cases with other glomerular diseases, from nine tertiary hospitals. Hazard ratios (HRs) were calculated using a Cox regression model to assess the risk of kidney disease progression, defined as either ≥ 50% decrease in estimated glomerular filtration rates or the development of end-stage kidney disease, based on the presence of glomerular crescents. RESULTS: Out of the 327 patients selected, ten patients had glomerular crescents observed in their biopsied tissues. Over the follow-up period (median of 19 months, with a maximum of 18 years), the crescent group exhibited a higher risk of kidney disease progression than the no crescent group, with an adjusted HR of 2.82 (1.32-6.06) (P = 0.008). The presence of heavy proteinuria was associated with an increased risk of developing glomerular crescents. CONCLUSION: The presence of glomerular crescents is indeed linked to the progression of type 2 DKD. Therefore, it is important to determine whether there is an additional immune-mediated glomerulonephritis requiring immunomodulation, and it may be prudent to monitor the histology and repeat a biopsy.

Prognostic factors for clinical outcomes after arthroscopic treatment of traumatic central tears of the triangular fibrocartilage complex.

Aims: The study aimed to assess the clinical outcomes of arthroscopic debridement and partial excision in patients with traumatic central tears of the triangular fibrocartilage complex (TFCC), and to identify prognostic factors associated with unfavourable clinical outcomes. Methods: A retrospective analysis was conducted on patients arthroscopically diagnosed with Palmer 1 A lesions who underwent arthroscopic debridement and partial excision from March 2009 to February 2021, with a minimum follow-up of 24 months. Patients were assessed using the Disabilities of the Arm, Shoulder and Hand (DASH) questionnaire, Mayo Wrist Score (MWS), and visual analogue scale (VAS) for pain. The poor outcome group was defined as patients whose preoperative and last follow-up clinical score difference was less than the minimal clinically important difference of the DASH score (10.83). Baseline characteristics, arthroscopic findings, and radiological factors (ulnar variance, MRI, or arthrography) were evaluated to predict poor clinical outcomes. Results: A total of 114 patients were enrolled in this study, with a mean follow-up period of 29.8 months (SD 14.4). The mean DASH score improved from 36.5 (SD 21.5) to 16.7 (SD 14.3), the mean MWS from 59.7 (SD 17.9) to 79.3 (SD 14.3), and the mean VAS pain score improved from 5.9 (SD 1.8) to 2.2 (SD 2.0) at the last follow-up (all p < 0.001). Among the 114 patients, 16 (14%) experienced poor clinical outcomes and ten (8.8%) required secondary ulnar shortening osteotomy. Positive ulnar variance was the only factor significantly associated with poor clinical outcomes (p < 0.001). Positive ulnar variance was present in 38 patients (33%); among them, eight patients (21%) required additional operations. Conclusion: Arthroscopic debridement alone appears to be an effective and safe initial treatment for patients with traumatic central TFCC tears. The presence of positive ulnar variance was associated with poor clinical outcomes, but close observation after arthroscopic debridement is more likely to be recommended than ulnar shortening osteotomy as a primary treatment.

A deep learning segmentation method to assess dose to organs at risk during breast radiotherapy.

Background and purpose: Contouring of organs at risk is important for studying health effects following breast radiotherapy. However, manual contouring is time-consuming and subject to variability. The purpose of this study was to develop a deep learning-based method to automatically segment multiple structures on breast radiotherapy planning computed tomography (CT) images. Materials and methods: We used data from 118 patients, including 90 diagnostic CT scans with expert structure delineations for training and 28 breast radiotherapy planning CT images for testing. The radiotherapy CT images also had expert delineations for evaluating performance. We targeted a total of eleven organs at risk including five heart substructures. Segmentation performance was evaluated using the metrics of Dice similarity coefficient (DSC), overlap fraction, volume similarity, Hausdorff distance, mean surface distance, and dose. Results: The average DSC achieved on the radiotherapy planning images was 0.94 ± 0.02 for the whole heart, 0.96 ± 0.02 and 0.97 ± 0.01 for the left and right lung, 0.61 ± 0.10 for the esophagus, 0.81 ± 0.04 and 0.86 ± 0.04 for left and right atrium, 0.91 ± 0.02 and 0.84 ± 0.04 for left and right ventricle, and 0.21 ± 0.11 for the left anterior descending artery (LAD), respectively. Except for the LAD, the median difference in mean dose to these structures was small with absolute (relative) differences < 0.1 Gy (6 %). Conclusions: Except for the LAD, our method demonstrated excellent performance and can be generalized to segment additional structures of interest.

CD5 Expression Dynamically Changes During the Differentiation of Human CD8+ T Cells Predicting Clinical Response to Immunotherapy.

Defining the molecular dynamics associated with T cell differentiation enhances our understanding of T cell biology and opens up new possibilities for clinical implications. In this study, we investigated the dynamics of CD5 expression in CD8+ T cell differentiation and explored its potential clinical uses. Using PBMCs from 29 healthy donors, we observed a stepwise decrease in CD5 expression as CD8+ T cells progressed through the differentiation stages. Interestingly, we found that CD5 expression was initially upregulated in response to T cell receptor stimulation, but diminished as the cells underwent proliferation, potentially explaining the differentiation-associated CD5 downregulation. Based on the proliferation-dependent downregulation of CD5, we hypothesized that relative CD5 expression could serve as a marker to distinguish the heterogeneous CD8+ T cell population based on their proliferation history. In support of this, we demonstrated that effector memory CD8+ T cells with higher CD5 expression exhibited phenotypic and functional characteristics resembling less differentiated cells compared to those with lower CD5 expression. Furthermore, in the retrospective analysis of PBMCs from 30 non-small cell lung cancer patients, we found that patients with higher CD5 expression in effector memory T cells displayed CD8+ T cells with a phenotype closer to the less differentiated cells, leading to favorable clinical outcomes in response to immune checkpoint inhibitor (ICI) therapy. These findings highlight the dynamics of CD5 expression as an indicator of CD8+ T cell differentiation status, and have implications for the development of predictive biomarker for ICI therapy.

ATF6 is a critical regulator of cadmium-mediated apoptosis in spermatocytes.

In this study, we examined the mechanisms of cadmium exposure-induced endoplasmic reticulum (ER) stress response and apoptosis in spermatocytes. Responses to cadmium toxicity were investigated using spermatocytes overexpressing p50ATF6, ATF4, and spliced XBP1s, belonging to the 3 unfolded protein response pathways. The ER stress and apoptosis response to cadmium were most strongly stimulated through the activating transcription factor 6 (ATF6) pathway; in contrast, siRNA-induced inhibition of protein expression could reduce apoptosis under stressful conditions. An in vivo experiment using mice confirmed that upregulation of p50ATF6 in the testis increased apoptosis in response to cadmium exposure. Further, when confirming the correlation between ER stress and MAPK in cadmium toxicity, p38 MAPK phosphorylation was strongly regulated by p50ATF6; p-p38 also mediated the activity of p50ATF6. Overall, these findings suggest that modulating the activity of p38 MAPK and p50ATF6 in cadmium exposure-induced toxicity can be considered a potential strategy to treat infertility.

Blood-Based Biomarker Analysis for Predicting Efficacy of Chemoradiotherapy and Durvalumab in Patients with Unresectable Stage III Non-Small Cell Lung Cancer.

We recruited 50 patients with unresectable stage III NSCLC who received CCRT between March 2020 and March 2021. Durvalumab consolidation (DC) was administered to patients (n = 23) without progression after CCRT and programmed death-ligand 1 (PD-L1) ≥ 1%. Blood samples were collected before (C0) and after CCRT (C1) to calculate PBC counts and analyze CTCs. CTCs, isolated by the CD-PRIMETM system, exhibited EpCAM/CK+/CD45- phenotype in BioViewCCBSTM. At median follow-up of 27.4 months, patients with residual CTC clusters at C1 had worse median PFS than those without a detectable CTC cluster (11.0 vs. 27.8 months, p = 0.032), and this trend was noted only in the DC group (p = 0.034). Patients with high platelets at C1 (PLThi, >252 × 103/µL) had worse median PFS than those with low platelets (PLTlo) (5.9 vs. 17.1 months, p < 0.001). In multivariable analysis, PLThi and residual CTC clusters at C1 were independent risk factors for PFS, and DC group with PLThi and residual CTC clusters at C1 showed the worst median PFS (2.6 months, HR 45.16, p = 0.001), even worse than that of the CCRT alone group with PLThi (5.9 months, HR 15.39, p = 0.001). The comprehensive analysis of CTCs and PBCs before and after CCRT revealed that the clearance of CTC clusters and platelet counts at C1 might be potential biomarkers for predicting survival.

Self-rated health and the risk of incident chronic kidney disease: a community-based Korean study.

BACKGROUND: The relationship between self-rated health (SRH) and the development of incident chronic kidney disease (CKD) has not been explored in the general population. METHODS: We reviewed the data of 7027 participants in the Ansung-Ansan cohort study. SRH was categorized as poor, fair, or good, and the outcome was the development of CKD, defined as the first event of an estimated glomerular filtration rate < 60 mL/min/1.73 m2, at least twice during the follow-up period. Hazard ratios (HRs) and confidence intervals (CIs) were calculated using Cox proportional hazards regression analysis. RESULTS: Over a mean follow-up duration of 11.9 years, 951 participants (13.5%) developed CKD. Compared with poor self-rated health, the HR (95% CI) of fair self-rated health for incident CKD development was 0.771 (0.657-0.905; P = 0.001), whereas that of good self-rated health was 0.795 (0.676-0.935; P = 0.006). However, the renal hazard of good self-rated health did not differ from that of fair self-rated health. In the fully adjusted model, the HR (95% CI) of poor self-rated health compared to non-poor self-rated health for incident CKD was 1.278 (1.114-1.465, P < 0.001). Old age, smoking, cardiovascular disease, diabetes, hypertension, impaired sleep, and high levels of C-reactive protein and white blood cell counts were associated with increased odds of poor self-rated health, whereas male sex, college graduate level of education, and alcohol consumption were associated with decreased odds of poor self-rated health. CONCLUSION: Poor self-rated health is independently associated with CKD development. Therefore, the early detection of potential CKD patients through a brief questionnaire assessment may help control the incidence of CKD.

Peroxiredoxin 2 Ameliorates AßO-Mediated Autophagy by Inhibiting ROS via the ROS-NRF2-p62 Pathway in N2a-APP Swedish Cells.

In Alzheimer's disease, reactive oxygen species (ROS) are generated by the deposition of amyloid-beta oligomers (AßOs), which represent one of the important causes of neuronal cell death. Additionally, AßOs are known to induce autophagy via ROS induction. Previous studies have shown that autophagy upregulation aggravates neuronal cell death. In this study, the effects of peroxiredoxin 2 (Prx2), a member of the peroxidase family of antioxidant enzymes, on regulating AßO-mediated autophagy were investigated. Prx2 decreased AßO-mediated oxidative stress and autophagy in N2a-APPswe cells. Further, we examined the relationship between the neuronal protective effect of Prx2 and a decrease in autophagy. Similar to the effects of N-acetyl cysteine, Prx2 decreased AßO-induced ROS and inhibited p62 protein expression levels by downregulating the activation of NRF2 and its translocation to the nucleus. In addition, treatment with 3-methyladenine, an autophagy inhibitor, ameliorates neuronal cell death. Overall, these results demonstrate that the Prx2-induced decrease in autophagy was associated with the inhibition of ROS via the ROS-NRF2-p62 pathway in N2a-APPswe cells. Therefore, our results revealed that Prx2 is a potential therapeutic target in anti-Alzheimer therapy.

Readiness for Radiation Treatment Continuity: Survey on Contingency Plans Against Cyberattacks.

Purpose: Cyberattacks on health care systems have been on the rise over the past 5 years. Formulation and implementation of a robust postattack business continuity plan and/or contingency plan (CP) is essential for minimal disruption to patient care. The level of awareness and planning within the radiation oncology community for cyberattacks is not clear. This study was undertaken to survey and assess cyberattack CP awareness and preparedness. Methods and Materials: A survey instrument comprising 5 questions on awareness and preparedness of cyberattack CPs was e-mailed to 150 radiation oncology departments. Recipients included 105 institutions with residency programs in therapeutic medical physics, as listed by the Commission on Accreditation of Medical Physics Education Program (usually either school-based or large institutional settings), and 45 additional smaller settings within the United States, representing community practices. Results: Forty-three responses were deemed evaluable for analysis. Forty-two percent (18 respondents) of respondents responded that they are well-aware of the concept of a cyberattack CP. A large discrepancy in awareness exists between larger hospitals (LH) that have 5 or more treatment machines and smaller hospitals (SH) that have 4 or fewer, 54% versus 24 % (P < .05). Fifty-eight percent of respondents considered it "essential" to have such a plan in place, and 28% considered it "desirable" to do so but not practical. Nine percent regarded a cyberattack CP as unnecessary. No significant differences in responses were noted among different types or sizes of institutions on this issue. Sixty-two percent of LH responded that they were either preparing or evaluating a CP, compared with only 29% of SH (P = .03). However, no respondents explicitly replied that they already had a CP in place in their practices. Conclusions: The importance of cyberattack preparedness and implementation does not seem to be well-recognized in radiation oncology. Both the awareness and the preparedness of SH are substantially less than those of LH. Specific and ongoing education efforts in parallel with development of appropriate programs are needed to counter the increasingly pervasive and complex threat of cyberattacks.

Is a weekly qualitative picket fence test sufficient? A proposed alternate EPID-based weekly MLC QA program.

PURPOSE: Well-designed routine multileaf collimator (MLC) quality assurance (QA) is important to assure external-beam radiation treatment delivery accuracy. This study evaluates the clinical necessity of a comprehensive weekly (C-Weekly) MLC QA program compared to the American Association of Physics in Medicinerecommended weekly picket fence test (PF-Weekly), based on our seven-year experience with weekly MLC QA. METHODS: The C-Weekly MLC QA program used in this study includes 5 tests to analyze: (1) absolute MLC leaf position; (2) interdigitation MLC leaf position; (3) picket fence MLC leaf positions at static gantry angle; (4) minimum leaf-gap setting; and (5) volumetric-modulated arc therapy delivery. A total of 20,226 QA images from 16,855 tests (3,371 tests × 5) for 11 linacs at 5 photon clinical sites from May 2014 to June 2021 were analyzed. Failure mode and effects analysis was performed with 5 failure modes related to the 5 tests. For each failure mode, a risk probability number (RPN) was calculated for a C-Weekly and a PF-Weekly MLC QA program. The probability of occurrence was evaluated from statistical analyses of the C-Weekly MLC QA. RESULTS: The total number of failures for these 16,855 tests was 143 (0.9%): 39 (27.3%) for absolute MLC leaf position, 13 (9.1%) for interdigitation position, 9 (6.3%) for static gantry picket fence, 2 (1.4%) for minimum leaf-gap setting, and 80 (55.9%) for VMAT delivery. RPN scores for PF-Weekly MLC QA ranged from 60 to 192 and from 48 to 96 for C-Weekly MLC QA. CONCLUSION: RPNs for the 5 failure modes of MLC QA tests were quantitatively determined and analyzed. A comprehensive weekly MLC QA is imperative to lower the RPNs of the 5 failure modes to the desired level (<125); those from the PF-Weekly MLC QA program were found to be higher (>125). This supports the clinical necessity for comprehensive weekly MLC QA.

Clinical Value of Serum Mitochondria-Inhibiting Substances in Assessing Renal Hazards: A Community-Based Prospective Study in Korea.

BACKGROUND: Mitochondrial dysfunction is strongly associated with several kidney diseases. However, no studies have evaluated the potential renal hazards of serum mitochondria-inhibiting substance (MIS) and aryl hydrocarbon receptor ligand (AhRL) levels. METHODS: We used serum level of MIS and AhRL and clinical renal outcomes from 1,511 participants of a prospective community-based cohort in Ansung. MIS was evaluated based on intracellular adenosine triphosphate (MIS-ATP) or reactive oxygen species (MIS-ROS) generation measured using cell-based assays. RESULTS: During a mean 6.9-year follow-up, 84 participants (5.6%) developed a rapid decline in kidney function. In the lowest quartile group of MIS-ATP, patients were older and had metabolically deleterious parameters. In multivariate logistic regression analysis, higher MIS-ATP was associated with decreased odds for rapid decline: the odds ratio (OR) of 1% increase was 0.977 (95% confidence interval [CI], 0.957 to 0.998; P=0.031), while higher MIS-ROS was marginally associated with increased odds for rapid decline (OR, 1.014; 95% CI, 0.999 to 1.028; P=0.055). However, serum AhRL was not associated with the rapid decline in kidney function. In subgroup analysis, the renal hazard of MIS was particularly evident in people with hypertension and low baseline kidney function. CONCLUSION: Serum MIS was independently associated with a rapid decline in kidney function, while serum AhRL was not. The clinical implication of renal hazard on serum MIS requires further evaluation in future studies.

CD8+ TILs in NSCLC differentiate into TEMRA via a bifurcated trajectory: deciphering immunogenicity of tumor antigens.

BACKGROUND: CD8+ tumor-infiltrating lymphocytes (TILs) comprise phenotypically and functionally heterogeneous subpopulations. Of these, effector memory CD45RA re-expressing CD8+ T cells (Temra) have been discovered and characterized as the most terminally differentiated subset. However, their exact ontogeny and physiological importance in association with tumor progression remain poorly understood. METHODS: We analyzed primary tumors and peripheral blood samples from 26 patients with non-small cell lung cancer and analyzed their phenotypes and functional characteristics using flow cytometry, RNA-sequencing, and bioinformatics. RESULTS: We found that tumor-infiltrating Temra (tilTemra) cells largely differ from peripheral blood Temra (pTemra), with distinct transcriptomes and functional properties. Notably, although majority of the pTemra was CD27-CD28- double-negative (DN), a large fraction of tilTemra population was CD27+CD28+ double-positive (DP), a characteristic of early-stage, less differentiated effector cells. Trajectory analysis revealed that CD8+ TILs undergo a divergent sequence of events for differentiation into either DP or DN tilTemra. Such a differentiation toward DP tilTemra relied on persistent expression of CD27 and CD28 and was associated with weak T cell receptor engagement. Thus, a higher proportion of DP Temra was correlated with lower immunogenicity of tumor antigens and consequently lower accumulation of CD8+ TILs. CONCLUSIONS: These data suggest a complex interplay between CD8+ T cells and tumors and define DP Temra as a unique subset of tumor-specific CD8+ TILs that are produced in patients with relatively low immunogenic cancer types, predicting immunogenicity of tumor antigens and CD8+ TIL counts, a reliable biomarker for successful cancer immunotherapy.

Polypharmacy and the Progression of Chronic Kidney Disease: Korean Cohort Study for Outcome in Patients with Chronic Kidney Disease.

INTRODUCTION: The renal hazard of polypharmacy has never been evaluated in predialysis chronic kidney disease (CKD) patients. OBJECTIVE: We aimed to analyze the renal hazard of polypharmacy in predialysis CKD patients with stage 1-5. METHOD: The data of 2,238 patients from a large-scale multicenter prospective Korean study (2011-2016), excluding 325 patients with various missing data, were reviewed. Polypharmacy was defined as taking 6 or more medications at the time of enrollment; renal events were defined as a ≥50% decrease in kidney function from baseline values, doubling of the serum creatinine levels, or initiation of renal replacement treatment. Hazard ratio (HR) and 95% confidence interval (CI) were calculated using Cox proportional-hazard regression analysis. RESULTS: Of the 1,913 patients, the mean estimated glomerular filtration rate was 53.6 mL/min/1.73 m2. The mean medication count was 4.1, and the prevalence of polypharmacy was 27.1%. During the average period of 3.6 years, 520 patients developed renal events (27.2%). Although increased medication counts were associated with increased renal hazard with HR (95% CI) of 1.056 (1.007-1.107, p = 0.025), even after adjusting for various confounders, adding comorbidity score and kidney function nullified the statistical significance. In mediation analysis, 55.6% (p = 0.016) of renal hazard in increased medication counts was mediated by the kidney function, and there was no direct effect of medication counts on renal event development. In subgroup analysis, the renal hazard of the medication counts was evident only in stage 1-3 of CKD patients (p for interaction = 0.014). CONCLUSIONS: We cannot identify the direct renal hazard of multiple medications, and most of the potential renal hazard was derived from intimate relationship with disease burden and kidney function.

Emergency Department as the Entry Point to Inpatient Care: A Nationwide, Population-Based Study in South Korea, 2016-2018.

(1) Background: The emergency department provides lifesaving treatment and has become an entry point to hospital admission. The purpose of our study was to describe the characteristics and outcomes of patients who were admitted through the emergency department to the intensive care unit or general ward. (2) Methods: We performed a retrospective, cross-sectional, descriptive analysis using the National Emergency Department Information System, analyzing patient data including disease category, diagnosis, and mortality from 1 January 2016, to 31 December 2018. (3) Results: During the study period, about 13.6% were admitted through the emergency department. Of these, the overall in-hospital mortality was 4.6%. The frequent disease class for the intensive care unit admissions was the cardiovascular system, and the classes for the general ward admissions were as follows: injury and toxicology, digestive system, and respiratory system. Cardiovascular system-related emergencies were the predominant cause of death among patients admitted to the intensive care unit; however, oncologic complications were the leading cause of death in the general ward. (4) Conclusions: Emergency departments are incrementally utilized as the entry point for hospital admission. Health care providers need to understand emergency department admission epidemiology and prepare for managing patients with certain common diagnoses.

Toward automation of initial chart check for photon/electron EBRT: the clinical implementation of new AAPM task group reports and automation techniques.

PURPOSE: The recently published AAPM TG-275 and the public review version of TG-315 list new recommendations for comprehensive and minimum physics initial chart checks, respectively. This article addresses the potential development and benefit of initial chart check automation when these recommendations are implemented for clinical photon/electron EBRT. METHODS: Eight board-certified physicists with 2-20 years of clinical experience performed initial chart checks using checklists from TG-275 and TG-315. Manual check times were estimated for three types of plans (IMRT/VMAT, 3D, and 2D) and for prostate, whole pelvis, lung, breast, head and neck, and brain cancers. An expert development team of three physicists re-evaluated the automation feasibility of TG-275 checklist based on their experience of developing and implementing the in-house and the commercial automation tools in our institution. Three levels of initial chart check automation were simulated: (1) Auto_UMMS_tool (which consists of in-house program and commercially available software); (2) Auto_TG275 (with full and partial automation as indicated in TG-275); and (3) Auto_UMMS_exp (with full and partial automation as determined by our experts' re-evaluation). RESULTS: With no automation of initial chart checks, the ranges of manual check times were 29-56 min (full TG-315 list) and 102-163 min (full TG-275 list), which varied significantly with physicists but varied little at different tumor sites. The 69 of 71 checks which were considered as "not fully automated" in TG-275 were re-evaluated with more automation feasibility. Compared to no automation, the higher levels of automation yielded a great reduction in both manual check times (by 44%-98%) and potentially residual detectable errors (by 15-85%). CONCLUSION: The initial chart check automation greatly improves the practicality and efficiency of implementing the new TG recommendations. Revisiting the TG reports with new technology/practice updates may help develop and utilize more automation clinically.

Therapeutic effect of decellularized extracellular matrix-based hydrogel for radiation esophagitis by 3D printed esophageal stent.

Radiation esophagitis, the most common acute adverse effect of radiation therapy, leads to unwanted consequences including discomfort, pain, an even death. However, no direct cure exists for patients suffering from this condition, with the harmful effect of ingestion and acid reflux on the damaged esophageal mucosa remaining an unresolved problem. Through the delivery of the hydrogel with stent platform, we aimed to evaluate the regenerative capacity of a tissue-specific decellularized extracellular matrix (dECM) hydrogel on damaged tissues. For this, an esophagus-derived dECM (EdECM) was developed and shown to have superior biofunctionality and rheological properties, as well as physical stability, potentially providing a better microenvironment for tissue development. An EdECM hydrogel-loaded stent was sequentially fabricated using a rotating rod combined 3D printing system that showed structural stability and protected a loaded hydrogel during delivery. Finally, following stent implantation, the therapeutic effect of EdECM was examined in a radiation esophagitis rat model. Our findings demonstrate that EdECM hydrogel delivery via a stent platform can rapidly resolve an inflammatory response, thus promoting a pro-regenerative microenvironment. The results suggest a promising therapeutic strategy for the treatment of radiation esophagitis.

Current findings of kidney biopsy including nephropathy associated with hypertension and diabetes mellitus in Korea.

BACKGROUND/AIMS: This study aimed to investigate long-term temporal trends and outcomes of biopsy-proven kidney diseases in a multicenter kidney biopsy cohort, focusing on hypertension and diabetes, the leading causes of end-stage kidney disease (ESKD). METHODS: The study included a total of 21,426 patients who underwent kidney biopsy from 1979 to 2018 in 18 hospitals in Korea. We selected subgroups of adults with diabetes (n = 2,813) or clinically presumed hypertensive nephrosclerosis (HT-N, n = 2,917). Clinical, demographic, and laboratory data were collected in conjunction with pathologic findings. The prevalence of pathologically confirmed kidney diseases over time and their associations with clinical outcomes were evaluated. RESULTS: The prevalence of biopsy-proven diabetic nephropathy (DN) has increased significantly from 2.5% to 6.0% in the total cohort in the recent 30 years with an increase in the prevalence of diabetes. Approximately 68% of total diabetic patients had non-diabetic renal disease (NDRD); the proportion was retained since 2000s. DN showed a significantly higher risk of ESKD than NDRD (hazard ratio [HR], 1.59; 95% confidence interval [CI], 1.35 to 1.88). The prevalence of biopsy-proven HT-N remained < 2% in the total cohort for several decades. There was no difference in risks of ESKD between patients with or without biopsy-proven HT-N (HR, 0.93; 95% CI, 0.54 to 1.59). CONCLUSION: In recent decades, the prevalence of diabetes and DN has significantly increased in the kidney biopsy cohort, showing an increased risk of ESKD. Despite the large numbers of patients meeting the clinical criteria of HT-N, most of those were diagnosed with pathologic diagnoses other than HT-N.

The Association between Pulmonary Functions and Incident Diabetes: Longitudinal Analysis from the Ansung Cohort in Korea.

Background: We sought to explore whether reduced pulmonary function is an independent risk factor for incident diabetes in Koreans. Methods: We conducted a prospective cohort study of pulmonary function as a risk factor for incident diabetes using 10-year follow-up data from 3,864 middle-aged adults from the Ansung cohort study in Korea. The incidence of diabetes was assessed using both oral glucose tolerance tests and glycosylated hemoglobin levels. Results: During 37,118 person-years of follow-up, 583 participants developed diabetes (incidence rate: 15.7 per 1,000 person-years). The mean follow-up period was 8.0±3.7 years. Forced vital capacity (FVC; % predicted) and forced expiratory volume in 1 second (FEV1; % predicted) were significantly correlated with incident diabetes in a graded manner after adjustment for sex, age, smoking, exercise, and metabolic parameters. The adjusted hazard ratio (HR) and confidence interval (CI) for diabetes were 1.408 (1.106 to 1.792) and 1.469 (1.137 to 1.897) in the first quartiles of FVC and FEV1, respectively, when compared with the highest quartile. Furthermore, the FVC of the lowest first and second quartiles showed a significantly higher 10-year panel homeostasis model assessment of insulin resistance index, with differences of 0.095 (95% CI, 0.010 to 0.018; P=0.028) and 0.127 (95% CI, 0.044 to 0.210; P=0.003), respectively, when compared to the highest quartiles. Conclusion: FVC and FEV1 are independent risk factors for developing diabetes in Koreans. Pulmonary factors are possible risk factors for insulin resistance and diabetes.

Mechanistic and microkinetic study of non-oxidative methane coupling on a single-atom iron catalyst.

Non-oxidative methane coupling has promising economic potential, but the catalytic and radical reactions become complicated at high temperatures. Here, we investigate the mechanism of non-oxidative methane coupling on an iron single-atom catalyst using density functional theory, and evaluate the catalytic performance under various reaction conditions using microkinetic modelling and experiments. Under typical reaction conditions (1300 K and 1 bar), C-C coupling and subsequent dehydrogenation to produce ethylene shows comparable energetics between the gas-phase and catalytic pathways. However, the microkinetic analysis reveals that the iron single-atom catalyst converted methane to mainly CH3 and H2 at reaction temperatures above 1300 K, and acetylene production is dominant over ethylene production. The sensitivity analysis suggests that increasing the C2 hydrocarbon yield by optimising the reaction conditions is limited. The experimental results obtained at 1293 K are consistent with the theoretical estimation that acetylene is the main C2 product over the iron single-atom catalyst.

Hepcidin, iron indices and bone mineral metabolism in non-dialysis chronic kidney disease.

BACKGROUND: Few studies have examined the association between hepcidin, iron indices and bone mineral metabolism in non-dialysis chronic kidney disease (CKD) patients. METHODS: We reviewed the data of 2238 patients from a large-scale multicenter prospective Korean study (2011-16) and excluded 214 patients with missing data on markers and related medications of iron and bone mineral metabolism, hemoglobin, blood pressure and causes of CKD. Multivariate linear regression analysis was used to identify the association between iron and bone mineral metabolism. RESULTS: The proportion of CKD Stages 1-5 were 16.2, 18.7, 37.1, 21.6 and 6.4%, respectively. Per each 10% increase in transferrin saturation (TSAT), there was a 0.013 mmol/L decrease in phosphorus [95% confidence interval (CI) -0.021 to -0.004; P = 0.003] and a 0.022 nmol/L increase in logarithmic 25-hydroxyvitamin D (Ln-25OHD) levels (95% CI 0.005-0.040; P = 0.019). A 1 pmol/L increase in Ln-ferritin was associated with a 0.080 ng/L decrease in Ln-intact parathyroid hormone (Ln-iPTH; 95% CI -0.122 to -0.039; P < 0.001). Meanwhile, beta (95% CI) per 1 unit increase in phosphorus, Ln-25OHD and Ln-iPTH for the square root of the serum hepcidin were 0.594 (0.257-0.932; P = 0.001), -0.270 (-0.431 to -0.108; P = 0.001) and 0.115 (0.004-0.226; P = 0.042), respectively. In subgroup analysis, the relationship between phosphorus, 25OHD and hepcidin was strongest in the positive-inflammation group. CONCLUSIONS: Markers of bone mineral metabolism and iron status, including hepcidin, were closely correlated to each other. Potential mechanisms of the relationship warrant further studies.