A Retrospective Study About the Effectiveness of Anastomosis With a Polyglycolic Acid Sheet in Colorectal Cancer.

Introduction Anastomotic leakage is a serious complication in colon and rectal cancer surgeries, contributing to increased mortality rates and extended hospital stays. Despite various preventive measures, including intraoperative assessments and transanal drains, the incidence of anastomotic leakage remains a significant concern. This study investigates the potential efficacy of polyglycolic acid (PGA) sheets in reducing anastomotic leakage rates in gastrointestinal surgeries. Materials & methods A retrospective cohort study was conducted between January 2021 and January 2023 at Nagoya Tokushukai General Hospital, Ogaki Tokushukai Hospital, and Haibara General Hospital. A total of 239 patients undergoing colon or rectal cancer surgery were included. Anastomoses were performed with or without PGA sheets, and groups were compared using statistical analyses, including t-tests, Mann-Whitney U tests, and chi-square tests. The primary endpoint was the incidence of anastomotic leakage. Results Of the 239 patients, anastomotic leakage occurred in 14 (6%). The PGA use group (52 patients) showed no instances of anastomotic leakage while the PGA non-use group (187 patients) had 14 cases. Comparisons revealed significant differences in anastomotic leakage rates (p=0.04) between the two groups. Univariate analysis demonstrated a lower incidence of anastomotic leakage associated with PGA use (p=0.04). However, no significant differences were observed for transanal drainage (p=0.66), smoking (p=0.76), steroid use (p=1), and preoperative chemotherapy (p=0.07). Conclusion This study suggests that the use of PGA sheets in gastrointestinal anastomosis may contribute to a lower incidence of anastomotic leakage. The findings highlight the need for further prospective studies with a larger sample size, distinguishing between colon and rectum surgeries. Despite the limitations of this retrospective study, the observed reduction in anastomotic leakage frequency with PGA sheet use is noteworthy, emphasizing the potential significance of this approach in preventing a critical complication in colorectal surgeries.

Efficacy and safety of drug therapy for the prevention and treatment of chemotherapy-induced peripheral neuropathy: a protocol for a systematic review and network meta-analysis.

INTRODUCTION: Chemotherapy-induced peripheral neuropathy (CIPN) is one of the most common dose-limiting side effects of chemotherapeutic drugs. Numerous clinical trials of various targeted drugs for the prevention or treatment of CIPN have been conducted; however, previous systematic reviews with direct comparisons have failed to demonstrate the efficacy of these drugs in the prevention or treatment of CIPN. In addition, no systematic reviews have indirectly compared CIPN prevention and treatment. This article describes a protocol for evaluating the efficacy and safety of drug therapy for the prevention and treatment of CIPN. The results of the proposed systematic review with network meta-analysis (NMA) will provide new insights into the prevention and treatment of CIPN. METHODS AND ANALYSIS: We will conduct a literature search in MEDLINE, PubMed, Embase, Cochrane Central Register of Controlled Trials and ClinicalTrials.gov to find relevant articles published through January 2023. We will include studies that investigated the efficacy and safety of vitamin B12, goshajinkigan, non-steroidal anti-inflammatory analgesics, opioids, calcium and magnesium, antidepressants and anticonvulsants on CIPN. Two authors will individually screen the retrieved reports and review the full text based on the selection criteria. The primary outcome is the incidence and severity of CIPN. The risk of bias will be assessed using V.2.0 of the Cochrane risk-of-bias tool. We will apply a frequentist random-effects NMA model to pool effect sizes across trials using risk ratios and mean differences with their 95% CIs. Competing interventions will be ranked using the surface under cumulative ranking probabilities. Heterogeneity will be assessed using the heterogeneity variance τ2, Cochran's Q test and I² statistic. ETHICS AND DISSEMINATION: This review does not require ethical approval. The research will be published in a peer-reviewed journal. PROSPERO REGISTRATION NUMBER: CRD42022371829.

Identifying high-grade serous ovarian carcinoma-specific extracellular vesicles by polyketone-coated nanowires.

Cancer cell-derived extracellular vesicles (EVs) have unique protein profiles, making them promising targets as disease biomarkers. High-grade serous ovarian carcinoma (HGSOC) is the deadly subtype of epithelial ovarian cancer, and we aimed to identify HGSOC-specific membrane proteins. Small EVs (sEVs) and medium/large EVs (m/lEVs) from cell lines or patient serum and ascites were analyzed by LC-MS/MS, revealing that both EV subtypes had unique proteomic characteristics. Multivalidation steps identified FRα, Claudin-3, and TACSTD2 as HGSOC-specific sEV proteins, but m/lEV-associated candidates were not identified. In addition, for using a simple-to-use microfluidic device for EV isolation, polyketone-coated nanowires (pNWs) were developed, which efficiently purify sEVs from biofluids. Multiplexed array assays of sEVs isolated by pNW showed specific detectability in cancer patients and predicted clinical status. In summary, the HGSOC-specific marker detection by pNW are a promising platform as clinical biomarkers, and these insights provide detailed proteomic aspects of diverse EVs in HGSOC patients.

Mutation detection of urinary cell-free DNA via catch-and-release isolation on nanowires for liquid biopsy.

Cell-free DNA (cfDNA) and extracellular vesicles (EVs) are molecular biomarkers in liquid biopsies that can be applied for cancer detection, which are known to carry information on the necessary conditions for oncogenesis and cancer cell-specific activities after oncogenesis, respectively. Analyses for both cfDNA and EVs from the same body fluid can provide insights into screening and identifying the molecular subtypes of cancer; however, a major bottleneck is the lack of efficient and standardized techniques for the isolation of cfDNA and EVs from clinical specimens. Here, we achieved catch-and-release isolation by hydrogen bond-mediated binding of cfDNA in urine to zinc oxide (ZnO) nanowires, which also capture EVs by surface charge, and subsequently we identified genetic mutations in urinary cfDNA. The binding strength of hydrogen bonds between single-crystal ZnO nanowires and DNA was found to be equal to or larger than that of conventional hydrophobic interactions, suggesting the possibility of isolating trace amounts of cfDNA. Our results demonstrated that nanowire-based cancer screening assay can screen cancer and can identify the molecular subtypes of cancer in urine from brain tumor patients through EV analysis and cfDNA mutation analysis. We anticipate our method to be a starting point for more sophisticated diagnostic models of cancer screening and identification.

Association between serum iron markers, iron supplementation and cardiovascular morbidity in pre-dialysis chronic kidney disease.

BACKGROUND: The optimal range of serum iron markers and usefulness of iron supplementation are uncertain in patients with pre-dialysis chronic kidney disease (CKD). We investigated the association between serum iron indices and risk of cardiovascular disease (CVD) events and the effectiveness of iron supplementation using Chronic Kidney Disease Japan Cohort data. METHODS: We included 1416 patients ages 20-75 years with pre-dialysis CKD. The tested exposures were serum transferrin saturation and serum ferritin levels and the outcome measures were any cardiovascular event. Fine-Gray subdistribution hazard models were used to examine the association between serum iron indices and time to events. The multivariable fractional polynomial interaction approach was used to evaluate whether serum iron indices were effect modifiers of the association between iron supplementation and cardiovascular events. RESULTS: The overall incidence rate of CVD events for a median of 4.12 years was 26.7 events/1000 person-years. Patients with serum transferrin saturation <20% demonstrated an increased risk of CVD [subdistribution hazard ratio (HR) 2.13] and congestive heart failure (subdistribution HR 2.42). The magnitude of reduction in CVD risk with iron supplementation was greater in patients with lower transferrin saturations (P = .042). CONCLUSIONS: Maintaining transferrin saturation >20% and adequate iron supplementation may effectively reduce the risk of CVD events in patients with pre-dialysis CKD.

Biopsy-proven CKD etiology and outcomes: the Chronic Kidney Disease Japan Cohort (CKD-JAC) study.

BACKGROUND: The Kidney Disease: Improving Global Outcomes guidelines advocate the cause-glomerular filtration rate (GFR)-albuminuria (CGA) classification for predicting outcomes. However, there is a dearth of data supporting the use of the cause of chronic kidney disease. This study aimed to address how to incorporate a prior biopsy-proven diagnosis in outcome prediction. METHODS: We examined the association of biopsy-proven kidney disease diagnoses with kidney failure with replacement therapy (KFRT) and all-cause death before KFRT in patients with various biopsy-proven diagnoses (n = 778, analysis A) and patients with diabetes mellitus labeled with biopsy-proven diabetic nephropathy (DN), other biopsy-proven diseases and no biopsy (n = 1117, analysis B). RESULTS: In analysis A, adding biopsy-proven diagnoses to the GFR-albuminuria (GA) classification improved the prediction of 8-year incidence of KFRT and all-cause death significantly regarding integrated discrimination improvement and net reclassification index. Fine-Gray (FG) models with KFRT as a competing event showed significantly higher subdistribution hazard ratios (SHRs) for all-cause death in nephrosclerosis {4.12 [95% confidence interval (CI) 1.11-15.2)], focal segmental glomerulosclerosis [3.77 (95% CI 1.09-13.1)]} and membranous nephropathy (MN) [2.91 (95% CI 1.02-8.30)] than in immunoglobulin A nephropathy (IgAN), while the Cox model failed to show significant associations. Crescentic glomerulonephritis had the highest risk of all-cause death [SHR 5.90 (95% CI 2.05-17.0)]. MN had a significantly lower risk of KFRT than IgAN [SHR 0.45 (95% CI 0.24-0.84)]. In analysis B, other biopsy-proven diseases had a lower risk of KFRT than biopsy-proven DN in the FG model, with death as a competing event [SHR 0.62 (95% CI 0.39-0.97)]. CONCLUSIONS: The CGA classification is of greater value in predicting outcomes than the GA classification.

Granulocyte colony-stimulating factor-associated aortitis in a woman with breast cancer: a case report.

BACKGROUND: Granulocyte colony-stimulating factor (G-CSF) is increasingly used to prevent chemotherapy-associated febrile neutropenia. Generally, aortitis is not considered a side effect of G-CSF and is thought to be extremely rare. Aortitis is an inflammation of the aorta and occurs mainly in connective tissue diseases (Takayasu arteritis, giant cell arteritis, etc.) and infectious diseases (bacterial endocarditis, syphilis, etc.). We report herein a rare case of G-CSF associated with aortitis in a woman with breast cancer. CASE PRESENTATION: Here, we present a case involving a 63-year-old woman with luminal type stage IIa breast cancer. The patient's treatment was initiated with docetaxel and cyclophosphamide, with pegfilgrastim (PEG-G) as support. After PEG-G administration on day 3, the patient developed an intermittent fever of up to 39.4 °C on day 10 and visited our outpatient clinic on day 13 with persistent high fever. Laboratory tests revealed a high neutrophil count (14,000/µL) and a high C-reactive protein (CRP) level (42.8 mg/dL) without any other abnormalities. Contrast-enhanced computed tomography scanning revealed soft tissue thickening with weak enhancement around the wall of the thoraco-abdominal aorta, aortic arch and left subclavian artery. The patient did not respond to antimicrobial agents. On the basis of these observations, the patient was diagnosed with PEG-G-induced aortitis, and her condition rapidly improved without corticosteroids. CONCLUSIONS: Clinicians should be aware of aortitis as a potential complication in patients undergoing G-CSF chemotherapy. In cases with persistent high fever after PEG-G administration, and in the absence of infection, aortitis should be suspected.

Chronic Volume Overload Caused by Abdominal Aorto-Venocaval Shunt Provides Arrhythmogenic Substrates in the Rat Atrium.

Atrial enlargement is thought to provide arrhythmogenic substrates, leading to the induction of atrial fibrillation (AF). In this study, we investigated the anatomical, molecular biological, and electrophysiological characteristics of remodeled atria in an animal model with chronic volume overload. We used rats that underwent abdominal aorto-venocaval shunt (AVS) surgery. In the in vivo studies, marked changes in electrocardiogram parameters, such as the P-wave duration, PR interval, and QRS width, as well as prolongation of the atrial effective refractory period were observed 12 weeks after the creation of AVS (AVS-12W), which were undetected at 8 weeks postoperative (AVS-8W) despite obvious atrial and ventricular enlargement. Moreover, the duration of AF induced by burst pacing in the AVS-12W rats was significantly longer than that in the Sham and AVS-8W rats. In the isolated atria, a longer action potential duration at 90% repolarization was detected in the AVS-12W rats compared with that in the Sham group. The mRNA levels of the Kv and Kir channels in the right atrium were mostly upregulated in the AVS-8W rats but were downregulated in the AVS-12W rats. These results show that chronic volume overload caused by abdominal AVS provides arrhythmogenic substrates in the rat atrium. The difference in gene expression in the right atrium between the AVS-8W and AVS-12W rats may partly explain the acquisition of arrhythmogenicity.

Determine both the conformation and orientation of a specific residue in α-synuclein(61-95) even in monolayer by 13C isotopic label and p-polarized multiple-angle incidence resolution spectrometry (pMAIRS).

Protein's magic function stems from its structure and various analytical techniques have been developed for it. Among proteins, membrane proteins are encoded 20-30% of genomes, whereas cause challenges for many analytical techniques. For example, lots of membrane proteins cannot form single crystal structure required by X-ray crystallography. As for NMR, the measurements were hindered by the low tumbling rates of membrane (i.e., phospholipid bilayers) where membrane proteins exist. In addition, membrane proteins usually lay parallel to the surface of phospholipid bilayers or form transmembrane structure. No matter parallel or perpendicular to phospholipid bilayers surface, membrane proteins form monolayer structure which is also difficult for X-ray and NMR to provide high-resolution results. Because NMR and X-ray crystallography are the two major analytical techniques to address protein's structure, membrane proteins only contribute 2.4% to the solved protein databank. Surface FT-IR techniques can evaluate the conformation and orientation of membrane proteins by amide I band. Specifically for α-helical peptides/proteins, the orientation of the axis is critical to decide whether proteins form transmembrane structure. Notice that the traditional FT-IR can only provide "low-resolution" results. Here, 13C isotope was introduced into the nonamyloid component (NAC), which spans residues 61-95 of α-synuclein (α-syn). Then, p-polarized multiple-angle incidence resolution spectrometry (pMAIRS) was used to determine the orientation of a specific residue of α-helical NAC in monolayer. In general, pMAIRS is a novel technique to work complementary with X-ray and NMR to address membrane peptides/proteins structure with high resolution even in monolayer.

Effect of systemic bisphosphonate administration on patients with periodontal disease: a systematic review and meta-analysis protocol.

INTRODUCTION: Periodontal disease is a chronic oral infectious disease affecting adults worldwide as well as a lifestyle-related disease related to diabetes. Bisphosphonate is a drug often taken by patients with osteoporosis; however, it reportedly can cause jawbone necrosis. Due to its mechanism of action on bone tissue, bisphosphonate has been used topically on periodontal tissue to treat periodontal disease. However, the long-term systemic effects of bisphosphonates on periodontal tissues are unclear. This paper describes a protocol evaluating the effects of systemic bisphosphonate administration to prevent periodontal tissue destruction in patients with periodontal disease. No systematic review has attempted to summarise the evidence for systemic bisphosphonates in periodontal therapy. The results of the proposed systematic review will inform the practice and design of future clinical trials. METHODS AND ANALYSIS: This paper describes a protocol for a systematic review of the relevant published analytic research using an aggregative thematic approach according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols guidelines. Two authors will perform a comprehensive search for studies on Medline/PubMed, Scopus, Embase, LILACS and the Cochrane Central Register of Controlled Trials databases. Abstract screening, full-text screening and data extraction will be performed independently by two authors. A meta-analysis will be conducted as appropriate. ETHICS AND DISSEMINATION: The protocol of this systematic review will be provided in a peer-reviewed journal. Formal ethics approval is not necessary because researchers will not identify individuals in the report. PROSPERO REGISTRATION NUMBER: CRD42020212698 (http://www.crd.york.ac.uk/PROSPERO/).

Association between Dipeptidyl Peptidase-4 Inhibitor Prescription and Erythropoiesis-Stimulating Agent Hyporesponsiveness in Hemodialysis Patients with Diabetes Mellitus.

INTRODUCTION: Dipeptidyl peptidase-4 (DPP-4) has been hypothesized to improve responsiveness to erythropoiesis-stimulating agent (ESA). We aimed to describe the trend in DPP-4 inhibitor prescription patterns and assess the association between DPP-4 inhibitor prescription and ESA hyporesponsiveness (eHypo) in Japanese hemodialysis (HD) patients with diabetes mellitus (DM). METHODS: We analyzed data from the Japan Dialysis Outcomes and Practice Patterns Study phase 4-6 (2009-2017) on patients with DM who underwent HD thrice per week for at least 4 months. The primary exposure of interest was having a DPP-4 inhibitor prescription. The primary analysis outcomes were a binary indicator of eHypo (mean hemoglobin <10 and mean ESA dose >6,000 units/week over 4 months) and the natural log-transformed ESA resistance index (ERI). We used conditional logistic regression to compare within-patient changes in eHypo before and after initial DPP-4 inhibitor prescription. We used linear generalized estimating equation models to compare continuous ERI outcomes while accounting for within-patient repeated measurements with an exchangeable correlation structure. RESULTS: There was a monotonic increase in DPP-4 inhibitor prescription according to study year up to 20% in 2017. Moreover, 12.8% of patients with a DPP-4 inhibitor prescription were ESA hyporesponsive before the initial DPP-4 inhibitor prescription. After DPP-4 inhibitor prescription, the odds of eHypo and mean log-ERI remained unchanged in the whole cohort of our study. The interaction analysis of DPP-4 inhibitor and sideropenia showed that DPP-4 inhibitors attenuated eHypo in the patients without iron deficiency. CONCLUSION: Our findings indicate a recent increase in DPP-4 inhibitor prescription among Japanese HD patients with DM. DPP-4 inhibitors could improve ERI in patients undergoing HD without iron deficiency.

Aldosterone antagonists for people with chronic kidney disease requiring dialysis.

BACKGROUND: People with chronic kidney disease (CKD) requiring dialysis are at a particularly high risk of cardiovascular death and morbidity. Several clinical studies suggested that aldosterone antagonists would be a promising treatment option for people undergoing dialysis. However, the clinical efficacy and potential harm of aldosterone antagonists for people with CKD on dialysis has yet to be determined. OBJECTIVES: This review aimed to evaluate the benefits and harms of aldosterone antagonists, both non-selective (spironolactone) and selective (eplerenone), in comparison to control (placebo or standard care) in people with CKD requiring haemodialysis (HD) or peritoneal dialysis (PD). SEARCH METHODS: We searched the Cochrane Kidney and Transplant Register of Studies up to 5 August 2020 using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov. SELECTION CRITERIA: We included parallel randomised controlled trials (RCTs), cross-over RCTs, and quasi-RCTs (where group allocation is by a method that is not truly random, such as alternation, assignment based on alternate medical records, date of birth, case record number, or other predictable methods) that compared aldosterone antagonists with placebo or standard care in people with CKD requiring dialysis. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data and assessed risk of bias for included studies. We used a random-effects model meta-analysis to perform a quantitative synthesis of the data. We used the I² statistic to measure heterogeneity among the studies in each analysis. We indicated summary estimates as a risk ratio (RR) for dichotomous outcomes, mean difference (MD) for continuous outcomes, or standardised mean differences (SMD) if different scales were used, with their 95% confidence interval (CI). We assessed the certainty of the evidence for each of the main outcomes using the GRADE (Grades of Recommendation, Assessment, Development, and Evaluation) approach. MAIN RESULTS: We included 16 studies (14 parallel RCTs and two cross-over RCTs) involving a total of 1446 participants. Thirteen studies compared spironolactone to placebo or standard care and one study compared eplerenone to a placebo. Most included studies had an unclear or high risk of bias. Compared to control, aldosterone antagonists probably reduced the risk of death (any cause) for people with CKD requiring dialysis (9 studies, 1119 participants: RR 0.45, 95% CI 0.30 to 0.67; I² = 0%; moderate certainty of evidence). Aldosterone antagonist probably decreased the risk of death due to cardiovascular disease (6 studies, 908 participants: RR 0.37, 95% CI 0.22 to 0.64; I² = 0%; moderate certainty of evidence) and cardiovascular and cerebrovascular morbidity (3 studies, 328 participants: RR 0.38, 95% CI 0.18 to 0.76; I² = 0%; moderate certainty of evidence). While aldosterone antagonists probably increased risk of gynaecomastia compared with control (4 studies, 768 participants: RR 5.95, 95% CI 1.93 to 18.3; I² = 0%; moderate certainty of evidence), aldosterone antagonists may make little or no difference to the risk of hyperkalaemia (9 studies, 981 participants: RR 1.41, 95% CI 0.72 to 2.78; I² = 47%; low certainty of evidence). Aldosterone antagonists had a marginal effect on left ventricular mass among participants undergoing dialysis (8 studies, 633 participants: SMD -0.42, 95% CI -0.78 to 0.05; I² = 77%). In people with CKD requiring dialysis received aldosterone antagonists compared to control, there were 72 fewer deaths from all causes per 1000 participants (95% CI 47 to 98) with a number needed to treat for an additional beneficial outcome (NNTB) of 14 (95% CI 10 to 21) and for gynaecomastia were 26 events per 1000 participants (95% CI 15 to 39) with a number need to treat for an additional harmful outcome (NNTH) of 38 (95% CI 26 to 68). AUTHORS' CONCLUSIONS: Based on moderate certainty of the evidence, aldosterone antagonists probably reduces the risk of all-cause and cardiovascular death and probably reduces morbidity due to cardiovascular and cerebrovascular disease in people with CKD requiring dialysis. For the adverse effect of gynaecomastia, the risk was increased compared to control. For this outcome, the absolute risk was lower than the absolute risk of death. It is hoped the three large ongoing studies will provide better certainty of evidence.

Association of erythropoietin resistance and fibroblast growth factor 23 in dialysis patients: Results from the Japanese Dialysis Outcomes and Practice Patterns Study.

BACKGROUND: Fibroblast growth factor 23 (FGF23) plays an important role in chronic kidney disease (CKD)-related mineral and bone disorders. High FGF23 levels are associated with increased risk of anaemia in non-haemodialysis CKD patients. FGF23 also negatively regulates erythropoiesis in mice. We hypothesized that higher FGF23 levels are associated with increased erythropoietin hyporesponsiveness among haemodialysis patients. METHODS: The study included 1044 patients from the Japanese Dialysis Outcomes and Practice Patterns Study (J-DOPPS) phase 5 (2012-2015). The outcome was erythropoiesis-stimulating agent hyporesponsiveness (ESA-hypo), defined as mean Hgb <10 g/dL and standardized mean ESA dose >6000 u/week over 4 months following FGF23 measurement. The association between ESA-hypo and FGF23 was estimated using multivariable-adjusted logistic generalized estimating equation regression models. RESULTS: Patients with higher levels of FGF23 were younger and had higher levels of serum albumin, creatinine, albumin-corrected calcium, phosphorus, PTH, 25(OH)-vitamin D, and had higher percentages of intravenous (IV) iron, IV vitamin D and cinacalcet use. ESA-hypo was present in 144 patients (13.8%). Compared with the third quintile of FGF23 levels, the odds ratio (95% CI) of ESA-hypo was 2.14 (0.99, 4.62) and 1.74 (0.74, 4.11) for the first and fifth quintiles, respectively. CONCLUSION: The lowest and highest levels of FGF23 were associated with higher odds of ESA-hypo in patients on maintenance haemodialysis, although the associations were not statistically significant. The relationship between FGF23 and anaemia, and particularly the increased risks of ESA-hypo at low FGF23 levels which might be the result of energy saving, must be confirmed in larger clinical studies.

Glycated albumin and hemoglobin A1c levels and cause-specific mortality by patients' conditions among hemodialysis patients with diabetes: a 3-year nationwide cohort study.

INTRODUCTION: Differences in mortality and cause-specific mortality rates according to glycated albumin (GA) and hemoglobin A1c (HbA1c) levels among dialysis patients with diabetes based on hypoglycemic agent use and malnutrition status remain unclear. Here, we examine these associations using a nationwide cohort. RESEARCH DESIGN AND METHODS: We examined 40 417 dialysis patients with diabetes who met our inclusion criteria (female, 30.8%; mean age, 67.3±11.2 years; mean dialysis duration, 5.4±4.6 years). The Global Leadership Initiative on Malnutrition criteria were used to assess malnutrition. Adjusted HRs and 95% confidence limits were calculated for 3-year mortality after adjustment for 18 potential confounders. HRs and subdistribution HRs were used to explore cause-specific mortality. RESULTS: We found a linear association between 3-year mortality and GA levels only in patients with GA ≥18% and not in patients with low GA levels, with a U-shaped association between HbA1c levels and the lowest morality at an HbA1c 6.0%-6.3%. This association differed based on patient conditions and hypoglycemic agent use. If patients using hypoglycemic agents were malnourished, mortality was increased with GA ≥24% and HbA1c ≥8%. In addition, patients with GA ≥22% and HbA1c ≥7.6% had significantly higher infectious or cardiovascular mortality rates. On the other hand, an inverse association was found between GA or HbA1c levels and cancer mortality. Patients with GA ≤15.8% had a higher risk of cancer mortality, especially those not using hypoglycemic agents (HR 1.63 (1.00-2.66)). CONCLUSIONS: Target GA and HbA1c levels in dialysis patients may differ according to hypoglycemic agent use, nutritional status, and the presence of cancer. The levels may be higher in malnourished patients than in other patients, and a very low GA level in dialysis patients not taking hypoglycemic agents may be associated with a risk of cancer. TRIAL REGISTRATION NUMBER: UMIN000018641.

Screening tool for identifying adults with excessive salt intake among community-dwelling adults: a population-based cohort study.

BACKGROUND: Excessive salt intake is widely known to be a cause of hypertension, cardiovascular events, and so on. However, simple tools for screening excessive salt intake are lacking. OBJECTIVE: We aimed to develop a simple screening tool to identify community-dwelling adults with excessive salt intake. METHODS: The present study involved participants who received health check-ups in Fukushima, Japan, in 2016 and 2017. We defined data from the 2016 check-up as the derivation set, and data from those who received check-ups in 2017 but not 2016 as the validation set. The outcome measure was excessive salt intake, defined as the estimated daily salt intake of 1 SD or more. Candidate predictors associated with the outcome were extracted using the Delphi method by an expert panel and narrowed down with clinical expertise and stepwise backward selection. The screening tool was developed using a coefficient-based multivariable scoring method and externally validated. RESULTS: A total of 1101 participants were included in the derivation set and 249 in the validation set. At the conclusion of the deviation process, 8 predictors were selected and scored. The areas under the receiver operating characteristic curve for derivation and external validation were 0.70 (95% CI: 0.67, 0.74) and 0.71 (95% CI: 0.62, 0.80), respectively. The calibration slope and intercept for external validation were 1.16 and -0.03, respectively. CONCLUSION: We developed a screening tool to identify adults with excessive salt intake. By extracting groups with excessive salt intake, target populations needing intervention for salt reduction can be highlighted efficiently.

Long-Term Evaluation of Low-Dose Betamethasone for Ataxia Telangiectasia.

BACKGROUND: Ataxia telangiectasia is an autosomal recessive disorder characterized by cerebellar ataxia, telangiectases, immune defects, and a predisposition to malignancy. Quality of life is severely impaired by neurological symptoms. However, curative options for the neurological symptoms are limited. Recent studies have demonstrated short-term improvement in neurological symptoms with betamethasone therapy. However, the long-term and adverse effects of betamethasone are unclear. The aim of this study was to evaluate the long-term effects, benefits, and adverse effects of low-dose betamethasone in ataxia telangiectasia. METHODS: Six patients with ataxia telangiectasia received betamethasone at 0.02 mg/kg/day for two years. After cessation of betamethasone, the patients were observed for two additional years. Neurological assessments were performed, and adverse effects were monitored every three months throughout the four-year study period. RESULTS: Transient improvement of neurological symptom was observed in five of the six patients. However, after two years betamethasone treatment, only one of the six patients showed a slight improvement in the neurological score, one patient showed no change, and the neurological scores of the remaining four patients deteriorated. After the cessation of betamethasone treatment, neurological symptoms worsened in all patients. As an adverse effect of betamethasone, transient adrenal dysfunction was observed in all cases. CONCLUSIONS: Although these findings are in agreement with previous studies suggesting that short-term betamethasone treatment transiently benefits patients with ataxia telangiectasia, the long-term benefits and risks should be carefully considered.

Rational Method of Monitoring Molecular Transformations on Metal-Oxide Nanowire Surfaces.

Metal-oxide nanowires have demonstrated excellent capability in the electrical detection of various molecules based on their material robustness in liquid and air environments. Although the surface structure of the nanowires essentially determines their interaction with adsorbed molecules, understanding the correlation between an oxide nanowire surface and an adsorbed molecule is still a major challenge. Herein, we propose a rational methodology to obtain this information for low-density molecules adsorbed on metal oxide nanowire surfaces by employing infrared p-polarized multiple-angle incidence resolution spectroscopy and temperature-programmed desorption/gas chromatography-mass spectrometry. As a model system, we studied the surface chemical transformation of an aldehyde (nonanal, a cancer biomarker in breath) on single-crystalline ZnO nanowires. We found that a slight surface reconstruction, induced by the thermal pretreatment, determines the surface chemical reactivity of nonanal. The present results show that the observed surface reaction trend can be interpreted in terms of the density of Zn ions exposed on the nanowire surface and of their corresponding spatial arrangement on the surface, which promotes the reaction between neighboring adsorbed molecules. The proposed methodology will support a better understanding of complex molecular transformations on various nanostructured metal-oxide surfaces.

Clinical prediction models for progression of chronic kidney disease to end-stage kidney failure under pre-dialysis nephrology care: results from the Chronic Kidney Disease Japan Cohort Study.

BACKGROUND: Reliable prediction tools are needed to identify patients with chronic kidney disease (CKD) at greater risk of developing end-stage kidney failure (ESKF). We developed and validated clinical prediction models (CPMs) for CKD progression to ESKF under pre-dialysis nephrology care using CKD-Japan Cohort (CKD-JAC) data. METHODS: We prospectively followed up 2034 participants with CKD, defined as an estimated glomerular filtration rate (eGFR) less than 60 mL/min/1.73 m2, aged 20-75 years for a mean of 3.15 years. We randomly divided the overall analysis set into development and validation cohorts. In the development cohort, CPMs were developed using Cox proportional hazard regression, and the goodness of fit was evaluated. In the validation cohort, discrimination and calibration of the developed CPMs were evaluated. We also validated developed CPMs in the dataset with the bootstrap method. RESULTS: ESKF onset was observed in 206 and 216 patients in the development (20.3%) and validation (21.2%) cohorts, respectively. Goodness of fit, discrimination, and calibration were worse for a simple model including age, sex, and eGFR than for a complicated model (plus albuminuria, systolic blood pressure, diabetes, serum albumin, and hemoglobin). The mean absolute difference between the observed and predictive probabilities of ESKF onset at 3 years was lower for the complicated model than for the simple model (1.57 vs. 1.87%). CONCLUSIONS: CPMs employing readily available data could precisely predict progression to ESKF in patients with CKD stage G3a to G5. These developed CPMs may facilitate more appropriate clinical care and shared decision-making between clinicians and patients.

Association between serum Na-Cl level and renal function decline in chronic kidney disease: results from the chronic kidney disease Japan cohort (CKD-JAC) study.

BACKGROUND: Metabolic acidosis, which reduces serum bicarbonate levels, contributes to the progression of chronic kidney disease (CKD). The difference between sodium and chloride (Na-Cl) may theoretically predict serum bicarbonate levels. This study aimed to evaluate serum Na-Cl level as a risk factor for renal function decline among patients who participated in the chronic kidney disease Japan cohort (CKD-JAC) study. METHODS: The association between low Na-Cl concentration (< 34 mmol/L) and composite renal function decline events (any initiation of renal replacement therapy or 50% decline in estimated glomerular filtration rate) was evaluated among 2143 patients with CKD stage G3a-4. Using Cox regression analysis, hazard ratios (HRs) were estimated after adjusting for the following covariates: age, sex, diabetes mellitus, diabetic nephropathy, cardiovascular disease, anemia, angiotensin-converting enzyme inhibitors and angiotensin II receptor antagonists, loop diuretics, cigarette smoking, body mass index, serum albumin, systolic blood pressure, urine albumin-to-creatinine ratio, and CKD stage. RESULTS: Composite renal function decline events were observed in 405 patients (18.9%) over the 4-year follow-up period. Low serum Na-Cl level (< 34 mmol/L) was independently associated with a greater risk for composite renal function decline events (HR 1.384; 95% confidence interval [CI], 1.116-1.717). Subgroup analyses identified that the association between low Na-Cl level and composite renal function decline events was stronger among patients with CKD stage G4 and those with anemia. CONCLUSIONS: Our investigation suggests that Na-Cl is an independent predictor of CKD progression, especially among patients with CKD stage G4 and those with anemia.

Anemia in conventional hemodialysis: Finding the optimal treatment balance.

Renal anemia is a serious and common complication in hemodialysis (HD) patients. The introduction of erythropoiesis-stimulating agents (ESAs) has dramatically improved hemoglobin levels and outcomes. Several interventional studies reported that excessive correction of anemia and the massive use of ESA can trigger cardiovascular disease (CVD), and consequently may worsen the prognosis of patients undergoing HD. Therefore, it has been widely recognized that large doses of ESA should be used with caution. An effective use of iron preparations is required to yield the optimal effect of ESA. It is well-known that iron utilization is inhibited under pathological conditions, such as chronic inflammation, resulting in ESA resistance. It is postulated that a new class of therapeutic agents for renal anemia, hypoxia inducible factor prolyl hydroxylase (HIF-PH) inhibitors, will have beneficial treatment effects in patients on HD. HIF is induced by hypoxia and promotes erythropoietin production. In the absence of a hypoxic state, HIF is decomposed by the HIF catabolic enzyme. HIF-PH inhibitors inhibit this degrading enzyme and stimulate endogenous erythropoietin production via HIF induction. Additionally, HIF-PH inhibitors promote effective utilization of iron and raise erythropoietin to physiological concentrations. Accordingly, HIF-PH inhibitors improve anemia and iron metabolism. It appears that this effect persists irrespective of chronic inflammatory conditions. HIF-PH inhibitors do not overshoot erythropoietin above physiological concentrations like ESAs. Therefore, it is hypothesized that HIF-PH inhibitors would not increase the risk of CVD in patients undergoing HD.