A retrospective study of the prevalence of isolated prolongation of activated partial thromboplastin time in the preoperative setting.

BACKGROUND: Isolated prolongation of activated partial thromboplastin time (APTT) has various causes including inheritable bleeding disorders, and has medical significance as it can lead to the cancelation of surgery. However, even an emergency surgery can be conducted in a patient presenting with severe APTT prolongation, provided careful evaluation and appropriate measures are taken. Hence, the identification of the underlying etiology of the prolonged APTT is crucial. To date, little evidence exists regarding the prevalence of isolated APTT prolongation in Japanese patients undergoing surgery. Herein, we aimed to clarify the prevalence of isolated prolongation of APTT in the preoperative setting and to identify the reasons underlying isolated, severely prolonged APTT. METHODS: Preoperative coagulation data of all elective and emergent patients who presented to the anesthetic department between January 1, 2020, and June 30, 2023, were retrospectively collected. Isolated prolongation of APTT was defined as an APTT ≥ 37 s with an international normalized ratio of prothrombin time < 1.2. The underlying etiology of the patient with isolated, severely prolonged APTT (≥ 46 s) was investigated, and canceled surgical procedures in relation to the isolated APTT prolongation were searched. RESULTS: Overall, 10,684 measurements from 9413 patients were included, of which 725 (6.8%) were identified as having isolated APTT prolongation. The reasons for the severely prolonged APTT (n = 60) were miscellaneous, with the most frequently detected etiology being antiphospholipid antibody positivity. Preoperative isolated APTT prolongation contributed to the cancellation of surgery in elective five cases. CONCLUSIONS: We clarified the prevalence of preoperative isolated prolongation of APTT. The presence of antiphospholipid antibody was the most frequently detected etiology of the patient with isolated, severely prolonged APTT. The present study provides an important dataset regarding the isolated prolongation of APTT in East Asian patients undergoing surgery.

Relationship between Lipoprotein Lipase Derived from Subcutaneous Adipose Tissue and Cardio-Ankle Vascular Index in Japanese Patients with Severe Obesity.

INTRODUCTION: Cardio-ankle vascular index (CAVI) is an arterial stiffness index that correlates inversely with body mass index (BMI) and subcutaneous fat area. Lipoprotein lipase (LPL) that catalyzes the hydrolysis of serum triglycerides is produced mainly in adipocytes. Serum LPL mass reflects LPL expression in adipose tissue, and its changes correlate inversely with changes in CAVI. We hypothesized that LPL derived from subcutaneous adipose tissue (SAT) suppresses the progression of arteriosclerosis and examined the relationship of LPL gene expression in different adipose tissues and serum LPL mass with CAVI in Japanese patients with severe obesity undergoing laparoscopic sleeve gastrectomy (LSG). METHODS: This study was a single-center retrospective database analysis. Fifty Japanese patients who underwent LSG and had 1-year postoperative follow-up data were enrolled (mean age 47.5 years, baseline BMI 46.6 kg/m2, baseline HbA1c 6.7%). SAT and visceral adipose tissue (VAT) samples were obtained during LSG surgery. LPL gene expression was analyzed by real-time PCR. Serum LPL mass was measured by ELISA using a specific monoclonal antibody against LPL. RESULTS: At baseline, LPL mRNA expression in SAT correlated positively with serum LPL mass, but LPL mRNA expression in VAT did not. LPL mRNA expression in SAT was correlated, and serum LPL mass tended to correlate inversely with the number of metabolic syndrome symptoms, but LPL mRNA expression in VAT did not. LPL mRNA expression in SAT and CAVI tended to correlate inversely in the group with visceral-to-subcutaneous fat ratio of 0.4 or higher, which is considered metabolically severe. Serum LPL mass increased 1 year after LSG. Change in serum LPL mass at 1 year after LSG tended to be an independent factor inversely associated with change in CAVI. CONCLUSIONS: Serum LPL mass reflected LPL mRNA expression in SAT in Japanese patients with severe obesity, and LPL mRNA expression in SAT was associated with CAVI in patients with visceral obesity. The change in serum LPL mass after LSG tended to independently contribute inversely to the change in CAVI. This study suggests that LPL derived from SAT may suppress the progression of arteriosclerosis.

Relationship of Serum Uric Acid with Kidney Function Decline Mediated by Systemic Arterial Stiffness: A Retrospective Cohort Study in Japan.

Hyperuricemia is associated with kidney function decline (KFD), although whether hyperuricemia directly causes nephrotoxicity or is indirectly mediated by systemic arterial stiffening remains unclear. We examined the detailed relationship of serum uric acid (SUA) with KFD and potential mediation by arterial stiffness. Study population was 27,648 urban residents with an estimated glomerular filtration rate (eGFR) of ≥60 mL/min/1.73 m2 at baseline, and they participated in a median of three consecutive annual health examinations. Arterial stiffness was assessed using cardio-ankle vascular index (CAVI). KFD was defined as a decrease in eGFR to below 60. Multivariate analysis showed an association between baseline SUA and CAVI independent of eGFR. During the study period, 6.6% of participants developed KFD. Stratified analysis revealed a linear relationship between the contribution of CAVI or SUA and KFD. ROC analysis determined a cutoff CAVI of 8.0 (males) or 7.9 (females) and a cutoff SUA of 6.3 (males) or 4.5 mg/dL (females) for predicting KFD. The linkage between SUA and CAVI was associated with a greater increase in the hazard ratio for KFD with an increase in SUA. CAVI showed the mediating effect on the relationship of SUA with KFD after an adjustment for confounders. SUA was associated positively with CAVI-mediated KFD. Further studies should verify whether intensive SUA-lowering treatment prevents KFD via improving vascular function.

Effects of Vildagliptin, a Dipeptidyl Peptidase-4 Inhibitor, on the Parameters of Glucose Metabolism and the Cardio-Ankle Vascular Index in Individuals with Type 2 Diabetes.

DPP-4 inhibitors are frequently used as first-line agents for the treatment of type 2 diabetes in Japan. This study aimed to examine the effects of vildagliptin on glucose metabolism and arterial stiffness. Twenty treatment-naïve patients with type 2 diabetes (8 males and 12 females) received vildagliptin 50 mg twice daily for 6 months. Self-monitored blood glucose measurements and a 75 g OGTT were performed. Arterial stiffness was assessed using the CAVI. After the vildagliptin treatment, a significant decrease in the median HbA1c (from 8.3 to 6.4%) and fasting HOMA-ß (from 26.1 to 34.5%), and a marginally significant decrease in the CAVI (from 8.9 to 8.4, p = 0.087) were observed. The glycemic variability parameters also improved, whereas the insulin sensitivity and oxidative stress remained unchanged. Participants with a lower glycemic variability on the 75 g OGTT after vildagliptin treatment showed a significant decrease in their CAVI. The baseline BMI was significantly higher for the participants with a decreased CAVI than in those with no change in their CAVI (24.5 vs. 20.8 kg/m2). After vildagliptin treatment, a decrease in the CAVI was observed, especially in the individuals with improved glycemic variability on the 75 g OGTT. Vildagliptin may be suitable for vascular protection in individuals with high glycemic variability and/or an elevated BMI.

Once-weekly semaglutide administered after laparoscopic sleeve gastrectomy: Effects on body weight, glycemic control, and measured nutritional metrics in Japanese patients having both obesity and type 2 diabetes.

Background: Glucagon-like peptide (GLP)-1 analogue may be useful for controlling weight recurrence and diabetes relapse after bariatric surgery, but may also adversely affect the measured nutritional metrics. This study aimed to investigate the effect of treatment with once-weekly semaglutide after laparoscopic sleeve gastrectomy (LSG) in patients with type 2 diabetes (T2D). We also examined the effects of combined use with a low-energy, high-protein formula diet (FD). Methods: This study was a single-center retrospective database analysis. We enrolled 29 Japanese patients with T2D who underwent LSG, and more than 12 months later received semaglutide. The patients were divided retrospectively into a FD group (=6) and a conventional diet (CD) group (n = 23). Results: BMI and HbA1c decreased significantly by 10.7 kg/m2 and 1.1 %, respectively, 12 months after LSG, and decreased by an additional 1.6 kg/m2 and 0.6 % after 12-months of treatment with semaglutide. Decreases in serum albumin, vitamin B12 and zinc were observed only after semaglutide administration. A ratio of energy from protein, fat and carbohydrates changed from 13:31:56 before to 19:30:50 after LSG, and from 17:32:51 before to 15:29:56 after semaglutide. Skeletal muscle ratio, which is the ratio of skeletal muscle mass to body weight, increased after LSG, but did not change after semaglutide. FD group showed a significant increase in skeletal muscle mass per 1 % body weight compared to CD group during semaglutide treatment. Conclusion: Semaglutide after LSG in patients with obesity and T2D resulted in additional weight reduction and improved glycemic control, but worsened measured nutritional metrics. Administration of a low-energy, high protein formula diet may ameliorate adverse nutritional effects of semaglutide in patients with T2D after LSG. (Ethics Committee of Toho University Sakura Medical Center approval number S18061).

Relationship of serum lipid parameters with kidney function decline accompanied by systemic arterial stiffness: a retrospective cohort study.

Background: Dyslipidemia is associated with kidney function decline (KFD), although the non-linear relationship of lipid parameters to KFD has not been fully elucidated. We aimed to determine the detailed relationship of baseline lipid parameters with KFD, considering the mediation of arterial stiffness. Methods: A total of 27 864 urban residents with estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m2 at baseline, who participated in a median of three (range two to eight) consecutive annual health examinations were studied. Arterial stiffness was assessed by cardio-ankle vascular index (CAVI). KFD was defined as development of eGFR <60 mL/min/1.73 m2. Results: During the study period, 1837 participants (6.6%) developed KFD. Receiver operating characteristic analysis determined that the cutoff values independently associated with KFD are 123 mg/dL for low-density lipoprotein cholesterol (LDL-C) [area under the curve (95% confidence interval) 0.570 (0.557-0.583)], 65 mg/dL for high-density lipoprotein cholesterol (HDL-C) [0.552 (0.539-0.566)], 82 mg/dL for triglycerides (TG) [0.606 (0.593-0.618)] and 1.28 for TG/HDL-C ratio [0.600 (0.587-0.612)]. These cut-offs were independently associated with KFD in Cox analysis. Regarding the contribution of each lipid parameter to KFD, a linear relationship was observed for both TG and TG/HDL-C, and a U-shaped relationship for HDL-C. A adjusted mediating effect of CAVI on the relationship of TG or TG/HDL-C ratio with KFD was observed (mediating rate: 2.9% in TG, 2.5% in TG/HDL-C ratio). Regarding the association to KFD, a linear relationship was observed for both TG and TG/HDL-C, and a U-shaped relationship for HDL-C. A mediating effect of CAVI on the relationship of TG or TG/HDL-C ratio with KFD was observed after adjustment for confounders. Conclusions: TG and TG/HDL-C ratio related linearly to KFD and this was partially mediated by CAVI. A U-shaped relationship was observed between HDL-C and KFD risk. LDL-C showed no significant association. Further study should investigate whether intensive TG-lowering treatment prevents KFD via decreasing CAVI.

A bioinformatic investigation of proteasome and autophagy expression in the central nervous system.

The ubiquitin proteasome system (UPS) and autophagy lysosome pathway (ALP) are crucial in the control of protein quality. However, data regarding the relative significance of UPS and ALP in the central nervous system (CNS) are limited. In the present study, using publicly available data, we computed the quantitative expression status of UPS- and ALP-related genes and their products in the CNS as compared with that in other tissues and cells. We obtained human and mouse gene expression datasets from the reference expression dataset (RefEx) and Genevestigator (a tool for handling curated transcriptomic data from public repositories) as well as human proteomics data from the proteomics database (ProteomicsDB). The expression levels of genes and proteins in four categories-ubiquitin, proteasome, autophagy, and lysosome--in the cells and tissues were assessed. Perturbation of the gene expression by drugs was also analyzed for the four categories. Compared with that for ubiquitin, autophagy, and lysosome, gene expression for proteasome was consistently lower in the CNS of mice but was more pronounced in humans. Neural stem cells and neurons showed low proteasome gene expression as compared with embryonic stem cells. Proteomic analyses, however, did not show trends similar to those observed in the gene expression analyses. Perturbation analyses revealed that azithromycin and vitamin D3 upregulated the expression of both UPS and ALP. Gene and proteomic expression data could offer a fresh perspective on CNS pathophysiology. Our results indicate that disproportional expression of UPS and ALP might affect CNS disorders and that this imbalance might be redressed by several therapeutic candidates.

Anesthetic Management of a Patient With Massive Pulmonary Secretion During Cardiopulmonary Bypass Probably Due to Transfusion-Related Acute Lung Injury Type â ¡.

Transfusion-related acute lung injury (TRALI) is potentially life-threatening adverse reaction associated with blood transfusion and can induce perioperative pulmonary secretion. TRALI that develops during cardiopulmonary bypass (CPB) may be difficult to detect; however, the pathophysiology might manifest as derangements in CPB operations. A 79-year-old man was scheduled to undergo partial replacement of the aortic arch with CPB. Two units of red blood cells were loaded into the priming solution. Although the vital signs, including oxygenation, remained stable in the prebypass period, perfusionists noticed a decreasing trend in the venous reservoir level early in the CPB operations. The trend continued even during circulatory arrest with selective cerebral perfusion, resulting in the termination of the modified hemofiltration. Surgical procedures were accomplished uneventfully; however, a large amount of fluid was required to maintain the minimal reservoir level and CPB flow. The total fluid balance during CPB was +8,233 mL, which was quite unusual in our practice. When 800 mL of massive pulmonary secretion was detected before CPB withdrawal, the etiology could not be determined simultaneously; nonetheless, systemic vascular hyperpermeability was speculated to be the underlying pathophysiology. Our therapeutic approach following the treatment of acute respiratory distress syndrome contributed to halting the deterioration of lung injury. Although the pneumothorax developed on the first postoperative day, the patient was treated with the insertion of a chest drainage tube. Subsequently, the patient had a good course and was discharged without respiratory complications. In conclusion, massive pulmonary secretion, probably due to TRALI type II, was associated with derangements in CPB operations. Prompt identification of the underlying pathophysiology and appropriate intervention is crucial.

Cumulative Cigarette Consumption is Associated with Cardio-Ankle Vascular Index (CAVI) Mediated by Abdominal Obesity Assessed by A Body Shape Index (ABSI): A Cross-Sectional Study.

AIM: To elucidate the mechanism by which cigarette smoking causes vascular damage, we examined the relationship between cumulative cigarette consumption and abdominal obesity, and the possible mediating effect of smoking on arterial stiffness. METHODS: Cross-sectional data from 19499 never smokers and 5406 current smokers receiving health screening was analyzed. Abdominal obesity was assessed by ABSI, and arterial stiffness by CAVI. High CAVI was defined as CAVI ≥ 9.0. RESULTS: Current smoker showed higher ABSI than never smokers after propensity score matching. Cumulative cigarette consumption expressed in pack-years correlated with ABSI (Rs: 0.312 in men, 0.252 in women), and was also extracted as an independent factor associated with ABSI by multiple regression analysis. A linear relationship between pack-year and CAVI was observed (Rs: 0.544 in men, 0.423 in women). Pack-year had almost equal discriminatory power in predicting high CAVI in both sexes (C-statistic: 0.774 in men, 0.747 in women), and the best cut-offs of pack-year for high CAVI were 24.5 in men and 14.7 in women. Bivariate logistic regression models revealed that the association between pack-year higher than cut-off and high CAVI was independent of traditional risks. A mediating effect of ABSI (mediation rate: 9.9% in men and 11.2% in women), but not waist circumference (WC), on the association of pack-year with CAVI was observed, after adjusting for traditional risks. CONCLUSION: Cumulative cigarette smoking in pack-years was independently associated with ABSI. ABSI partially mediates the association between pack-year and CAVI, suggesting that abdominal obesity partially mediates smoking-related vascular dysfunction.

Clinical availability of eye movement during reading.

Eyes provide valuable information for neurological diagnosis. So far, the use of diagnostic devices to analyze eye movement is limited. We explored whether the analysis of eye movements can be efficacious. Patients with Parkinson's disease (PD) (n = 29), spinocerebellar degeneration (SCD) (21), progressive supranuclear palsy (PSP) (19), and control individuals (19) participated in this study. The patients read aloud two sets of sentences displayed on a monitor: one was displayed horizontally, and the other vertically. Parameters such as eye movement speed, travel distance, and fixation/saccade ratio were extracted, and comparisons between groups were performed. Maneuvers of eye movements were also subjected to image classification using deep learning. Reading velocity and fixation/saccade ratio were altered in the PD group, and the SCD group exhibited ineffective eye movements due to dysmetria and nystagmus. Vertical gaze parameters showed aberrant values in the PSP group. Vertical written sentences were more sensitive than horizontal ones in detecting these abnormalities. In the regression analysis, vertical reading indicated a high accuracy in identifying each group. The machine learning analysis showed more than 90 % accuracy in distinguishing between the control and SCD groups and between the SCD and PSP groups. Analyzing eye movements is useful and easily applicable.

Soluble (Pro)Renin Receptor Level in Patients with Severe Obesity Is Associated with Visceral Adiposity and Is Involved with Insulin Resistance and Renal Injury.

INTRODUCTION: High soluble (pro)renin receptor (s[P]RR) level in circulation is reported in obese patients; however, it is unclear which body composition components are responsible for it. In this study, the authors examined blood s(P)RR levels and ATP6AP2 gene expression levels in visceral and subcutaneous adipose tissue (VAT, SAT) in severely obese patients who underwent laparoscopic sleeve gastrectomy (LSG), with the aim of clarifying the relationship with body composition and metabolic factors. METHODS: Seventy five cases who underwent LSG between 2011 and 2015 and were postoperatively followed-up for 12 months at the Toho University Sakura Medical Center were included in the analysis of the cross-sectional survey at baseline, and 33 cases were included in the analysis of the longitudinal survey during the 12 months after LSG. We evaluated body composition, glycolipid parameters, liver/renal function, as well as serum s(P)RR level and ATP6AP2 mRNA expression level in VAT and SAT. RESULTS: The mean serum s(P)RR level at baseline was 26.1 ng/mL, this value was considered higher than values in healthy subjects. There was no significant difference in the expression level of ATP6AP2 mRNA between VAT and SAT. At baseline, multiple regression analysis for the association between s(P)RR and variables identified that visceral fat area, HOMA2-IR, and UACR showed the independent relationships with s(P)RR. During the 12 months after LSG, body weight, serum s(P)RR level showed a significant decrease (from 30.0 ± 7.0 to 21.9 ± 4.3). Multiple regression analysis for the association between the change in s(P)RR and variables showed that changes in visceral fat area, and alanine transaminase were independently related to the change in s(P)RR. CONCLUSION: This study showed that blood s(P)RR level was high in severely obese patients, decreased with weight loss by LSG, and was associated with visceral fat area in both pre- and postoperative changes. The results suggest that blood s(P)RR levels in obese patients may reflect the involvement of visceral adipose (P)RR in insulin resistance and renal damage mechanisms associated with obesity.

Factors Associated with Relapse of Type 2 Diabetes Mellitus after Laparoscopic Sleeve Gastrectomy in Japanese Subjects: A Subgroup Analysis of J-SMART Study.

INTRODUCTION: Laparoscopic sleeve gastrectomy (LSG) for morbidly obese patients often results in remission of type 2 diabetes (T2DM), but diabetes relapses in some of those patients. The frequency of T2DM relapse in Asians and the factors involved have not been adequately investigated. METHODS: The J-SMART study was conducted on 322 Japanese subjects with body mass index (BMI) ≥32 kg/m2 who underwent LSG at 10 accredited centers in Japan between 2011 and 2014. Of these, 82 T2DM subjects with diabetes in complete or partial remission at 1 year after LSG and followed postoperatively for 5 years were included in the subgroup analysis and classified into two groups: diabetes remission-maintained and diabetes relapse. RESULTS: The mean age of all included subjects was 49.2 years, median BMI was 41.5 kg/m2, and median HbA1c was 6.7%. Compared with the diabetes remission-maintained group, the diabetes relapse group at 5 years after LSG had significantly higher preoperative HbA1c, number of antidiabetic medications, and high-density lipoprotein cholesterol level; and lower BMI and homeostasis model assessment-beta cell function (HOMA-ß). As many as 83.0% of the subjects were able to achieve HbA1c <7% at 5 years after LSG, but 26.8% of the subjects had diabetes relapse. Preoperative HbA1c significantly contributed to diabetes relapse (odds ratio 1.54, p = 0.049). In addition, the diabetes relapse group tended to have lower percentage total weight loss (%TWL) at 1 year after LSG and higher percentage weight regain (%WR) from postoperative nadir weight, compared with the diabetes remission-maintained group. The hazard ratio for diabetes relapse was 3.14-fold higher in subjects with %TWL ≥20% and %WR ≥25%, and 5.46-fold higher in those with %TWL <20% and %WR ≥25%, compared with %TWL ≥20% and %WR <25%. CONCLUSION: While LSG provides a high remission rate for T2DM, relapse is not uncommon. Preoperative HbA1c, poor weight loss, and excess weight regain after LSG contribute to diabetes relapse, suggesting the importance of treatment strategies focusing on these factors.

Safety and tolerability of bosutinib in patients with amyotrophic lateral sclerosis (iDReAM study): A multicentre, open-label, dose-escalation phase 1 trial.

Background: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease caused by the loss of motor neurons, and development of effective medicines is urgently required. Induced pluripotent stem cell (iPSC)-based drug repurposing identified the Src/c-Abl inhibitor bosutinib, which is approved for the treatment of chronic myelogenous leukemia (CML), as a candidate for the molecular targeted therapy of ALS. Methods: An open-label, multicentre, dose-escalation phase 1 study using a 3 + 3 design was conducted in 4 hospitals in Japan to evaluate the safety and tolerability of bosutinib in patients with ALS. Furthermore, the exploratory efficacy was evaluated using Revised ALS Functional Rating Scale (ALSFRS-R), predictive biomarkers including plasma neurofilament light chain (NFL) were explored, and single-cell RNA sequencing of iPSC-derived motor neurons was conducted. Patients, whose total ALSFRS-R scores decreased by 1-3 points during the 12-week, received escalating doses starting from 100 mg quaque die (QD) up to 400 mg QD based on dose-limiting toxicity (DLT) occurrence, and all participants who received one dose of the study drug were included in the primary analysis. This trial is registered with ClinicalTrials.gov, NCT04744532, as Induced pluripotent stem cell-based Drug Repurposing for Amyotrophic Lateral Sclerosis Medicine (iDReAM) study. Findings: Between March 29, 2019 and May 7, 2021, 20 patients were enrolled, 13 of whom received bosutinib treatment and 12 were included in the safety and efficacy analyses. No DLTs were observed up to 300 mg QD, but DLTs were observed in 3/3 patients of the 400 mg QD cohort. In all patients receiving 100 mg-400 mg, the prevalent adverse events (AEs) were gastrointestinal AEs in 12 patients (92.3%), liver function related AEs in 7 patients (53.8%), and rash in 3 patients (23.1%). The safety profile was consistent with that known for CML treatment, and ALS-specific AEs were not observed. A subset of patients (5/9 patients) was found to respond well to bosutinib treatment over the 12-week treatment period. It was found that the treatment-responsive patients could be distinguished by their lower levels of plasma NFL. Furthermore, single-cell RNA sequencing of iPSC-derived motor neurons revealed the pathogenesis related molecular signature in patients with ALS showing responsiveness to bosutinib. Interpretation: This is the first trial of a Src/c-Abl inhibitor, bosutinib, for patients with ALS. The safety and tolerability of bosutinib up to 300 mg, not 400 mg, in ALS were described, and responsiveness of patients on motor function was observed. Since this was an open-label trial within a short period with a limited number of patients, further clinical trials will be required. Funding: AMED and iPS Cell Research Fund.

A Body Shape Index (ABSI) as a Variant of Conicity Index Not Affected by the Obesity Paradox: A Cross-Sectional Study Using Arterial Stiffness Parameter.

A body shape index (ABSI) is an abdominal obesity index developed based on epidemiological statistics and designed to correlate minimally with body mass index (BMI). We examined the approximation between ABSI and other abdominal obesity indices based on biophysical concepts. The cross-sectional data from 62,514 Japanese urban residents were analyzed. Body adiposity indices comprising BMI, waist circumference (WC), ABSI, conicity index (CI), waist-to-height ratio (WHtR), and WC/BMI ratio were examined. ABSI and CI more strongly correlated with age and arterial stiffness assessed by cardio-ankle vascular index (CAVI) compared to the other indices. The discriminative power for high CAVI (≥9.0) was the strongest for ABSI followed by CI and other indices, in that order. The range and distribution of WC corresponding to the cutoff of ABSI (0.0801), or CI (1.23) seemed reasonable. The correlation between ABSI and CI was the strongest compared to any other combination of indices. CI correlated moderately with BMI, whereas ABSI correlated minimally with BMI. ABSI correlates strongly and approximates closely with CI. Hence, ABSI may be considered to reflect the degree of body shape change from cylindricity to conicity and is currently the only abdominal obesity index not affected by the obesity paradox.

Roles of microglia/macrophage and antibody in cell sheet transplantation in the central nervous system.

BACKGROUND: We previously established a human mesenchymal stem cell (MSC) line that was modified to express trophic factors. Transplanting a cell sheet produced from this line in an amyotrophic lateral sclerosis mouse model showed a beneficial trend for mouse life spans. However, the sheet survived for less than 14 days, and numerous microglia and macrophages were observed within and adjacent to the sheet. Here, we examined the roles of microglia and macrophages as well as acquired antibodies in cell sheet transplantation. METHODS: We observed the effects of several MSC lines on macrophages in vitro, that is, phenotype polarization (M1 or M2) and migration. We then investigated how phenotypic polarization affected MSC survival using antibody-dependent cellular cytotoxicity (ADCC) and phagocytosis (ADCP). We also confirmed the role of complement on cytotoxicity. Lastly, we selectively eliminated microglia and macrophages in vivo to determine whether these cells were cytoprotective to the donor sheet. RESULTS: In vitro co-culture with MSCs induced M2 polarization in macrophages and facilitated their migration toward MSCs in vitro. There was no difference between M1 and M2 phenotypes on ADCC and ADCP. Cytotoxicity was observed even in the absence of complement. Eliminating microglia/macrophage populations in vivo resulted in increased survival of donor cells after transplantation. CONCLUSIONS: Acquired antibodies played a role in ADCC and ADCP. MSCs induced M2 polarization in macrophages and facilitated their migration toward MSCs in vitro. Despite these favorable characteristics of microglia and macrophages, deletion of these cells was advantageous for the survival of donor cells in vivo.

Characteristics of Childhood Onset and Post-Puberty Onset Obesity and Weight Regain after Laparoscopic Sleeve Gastrectomy in Japanese Subjects: A Subgroup Analysis of J-SMART.

INTRODUCTION: The psychosocial background of subjects with severe obesity developed from childhood onset obesity (CO) and their outcomes after bariatric surgery have not been fully investigated. METHODS: 305 subjects were enrolled in the J-SMART study, which examined the effects of laparoscopic sleeve gastrectomy (LSG) in Japan, and categorized into two groups: CO defined as onset up to 13 years of age (CO group) and post-puberty onset obesity defined as onset after 13 years of age (PPO group). The subjects were followed up for at least 2 years and up to 5 years after LSG. Changes in physical parameters and remission of obesity-related comorbidities were assessed at 2 years after LSG. Weight regain (WR) was also assessed by evaluating the nadir weight after LSG and maximum weight thereafter during follow-up period. RESULTS: The mean postoperative follow-up period was 3.0 ± 1.1 years. 40.0% of the subjects had CO and these subjects had higher BMI and HOMA-ß and lower age, HbA1c, HDL cholesterol, and visceral/subcutaneous fat area ratio compared to those with PPO. The CO group was also characterized by having higher rates of mental retardation, developmental disorders, and obesity in either parent and lower rate of marriage compared to the PPO group. Two years after LSG, there were no differences in total weight loss and remission rates of diabetes, dyslipidemia, and sleep apnea syndrome between the two groups, although remission rate of hypertension was higher in the CO group. The CO group also had a higher rate of WR after LSG than the PPO group, with CO, BMI, mental disorder, and binge eating contributing to WR. CONCLUSION: This study suggests that CO might be associated with genetic and psychosocial factors. CO and PPO probably differ in pathogenesis and may require different treatment strategies.

Cardio-Ankle Vascular Index is Associated with Prevalence and New-Appearance of Atrial Fibrillation in Japanese Urban Residents: A Retrospective Cross-Sectional and Cohort Study.

AIM: Physiological tests to assess systemic vascular function are not included in the risk score for atrial fibrillation (AF). We aimed to examine whether cardio-ankle vascular index (CAVI), a systemic arterial stiffness parameter, is associated with the presence of AF in Japanese general population. METHODS: A cross-sectional study (N = 47,687) and a cohort study (N = 5418, four consecutive years) in Japanese urban residents who participated in annual health screening were conducted. RESULTS: A total of 164 subjects (0.34%) had AF in the cross-sectional data. After propensity score matching for age and gender, logistic regression analysis revealed that CAVI is independently associated with AF, as are body mass index and estimated glomerular filtration rate. In a 4-year cohort study, 22 subjects (0.41%) with new-appearance of AF showed higher CAVI at baseline than those without. In the receiver-operating-characteristic curve analysis, the area under the curve, which is a measure of predictability, of CAVI for the new-appearance of AF was 0.747, and the cut-off value of CAVI was 8.0. Kaplan-Meier analysis revealed that the cumulative incidence of new-appearance of AF was higher in subjects with CAVI ≥8.0 compared to those with CAVI <8.0. In Cox-proportional hazards analysis, CAVI ≥8.0 as well as gender were identified as independent predictors for the new-appearance of AF, whereas age ≥65 years was not. CONCLUSION: Increased CAVI may represent a major modifiable risk factor for the development of AF. Studies are needed to confirm that CAVI is a predictor of AF independent of various AF risk factors and that CAVI-lowering interventions can prevent new-appearance or recurrence of AF.

Preoperative Plasma Aldosterone Predicts Complete Remission of Type 2 Diabetes after Bariatric Surgery.

INTRODUCTION: Bariatric surgery (BS) has beneficial effects on body weight and type 2 diabetes. However, 44-52%, 20-40%, and 19-25% of patients with type 2 diabetes who undergo sleeve gastrectomy, sleeve gastrectomy with duodenal-jejunal bypass, and Roux-en-Y gastric bypass, respectively, show insufficient improvement 1 year after BS. It is thus important to predict the improvement in type 2 diabetes before BS. Many hormones are related to hyperglycemia. However, the relationship between hormones and improvement in type 2 diabetes after BS has not been studied. We aimed to evaluate the relationship between the improvement in type 2 diabetes and hormones in patients with obesity and type 2 diabetes who underwent BS. METHODS: We retrospectively reviewed 79 patients with obesity and type 2 diabetes who underwent BS, with a follow-up period of 12 months. We analyzed the relationship between some clinical parameters and complete remission (CR) of type 2 diabetes after BS. Patients were divided into two groups (type 2 diabetes CR and non-CR). Multiple regression analysis was performed to determine the parameters associated with type 2 diabetes resolution after BS. RESULTS: BS significantly improved body weight and glucose metabolism. Preoperative liver function, glycated hemoglobin (HbA1c), insulin secretion (homeostatic model assessment [HOMA]2-%B), renin activity, plasma aldosterone level, and duration of type 2 diabetes were significantly different between the CR and non-CR groups. Multiple regression analysis showed that preoperative HbA1c, HOMA2-%B, aldosterone concentration, and duration of type 2 diabetes were predictors of CR of type 2 diabetes after BS. Plasma aldosterone was the strongest predictor. DISCUSSION/CONCLUSION: Preoperative plasma aldosterone levels were related to the CR of type 2 diabetes after BS. Measuring plasma aldosterone levels preoperatively is useful for predicting the CR of type 2 diabetes after BS.

Issue of Waist Circumference for the Diagnosis of Metabolic Syndrome Regarding Arterial Stiffness: Possible Utility of a Body Shape Index in Middle-Aged Nonobese Japanese Urban Residents Receiving Health Screening.

INTRODUCTION: Abdominal obesity as a risk factor for diagnosing metabolic syndrome (MetS) is evaluated using waist circumference (WC), although WC does not necessarily reflect visceral adiposity. This cross-sectional study aimed to clarify whether replacing WC with "A Body Shape Index (ABSI)," an abdominal obesity index, in MetS diagnosis detects individuals with arterial stiffening assessed by cardio-ankle vascular index (CAVI). METHODS: A retrospective cross-sectional study was conducted in 46,872 Japanese urban residents (median age 40 years) who underwent health screening. Exclusion criteria were current treatments and a past history of cardiovascular disease (CVD). The Japanese, International Diabetes Federation, and NCEP-ATPIII criteria were used to diagnose MetS. High CAVI was defined as CAVI ≥9.0. RESULTS: CAVI correlated positively with ABSI (ß = 0.127), but negatively with WC (ß = -0.186), independent of age, sex, systolic blood pressure, fasting plasma glucose, and high-density lipoprotein--cholesterol. Receiver operating characteristic (ROC) analysis showed that ABSI had a stronger contribution to high CAVI (area under the ROC curve [AUC] = 0.730) than WC (AUC = 0.595) and body mass index (AUC = 0.520). ABSI ≥0.080 was defined as abdominal obesity based on the results of ROC analysis for high CAVI and estimated glomerular filtration rate <60 mL/min/1.73 m2. Logistic regression analysis revealed that replacing high WC with ABSI ≥0.080 in MetS diagnosis enhanced the detection of subjects with high CAVI. DISCUSSION/CONCLUSION: Use of ABSI can detect subjects with arterial stiffening, which may lead to efficient stratification of CVD risk. Further studies are needed to confirm whether MetS diagnosis using ABSI predicts CVD morbidity and mortality.