Ebina General Hospital

Introduction: Fibroblast growth factor 23 (FGF23) levels are markedly elevated in patients with kidney failure, but the mechanisms are incompletely understood. Recent evidence suggests that kidney-derived glycerol-3-phosphate (G-3-P), a glycolytic byproduct, mediates FGF23 production in response to dietary phosphate loading. However, the role of G-3-P is unknown in patients with kidney failure. Methods: Serum G-3-P levels were quantified by LC/MS in 35 healthy individuals and 650 patients undergoing hemodialysis. Association between serum phosphorus and G-3-P was examined using unadjusted and multivariable linear regression models. We next analyzed the associations of G-3-P and known regulators of FGF23 production with serum FGF23. Results: Median serum G-3-P level in patients undergoing hemodialysis was 220 ng/mL (IQR, 118–325), 2.2-fold higher than that of healthy individuals (98 ng/mL; IQR, 80–129). In patients undergoing hemodialysis, higher serum phosphorus was strongly associated with increased G-3-P in the unadjusted model; this association persisted after multivariate adjustment and when restricted to patients undergoing hemodialysis for over 10 years. In univariate analyses, higher serum phosphorus, calcium, intact PTH, G-3-P, and active vitamin D use were each significantly associated with higher FGF23. Multivariate analysis identified G-3-P as an independent predictor of FGF23. Further adjustment for transferrin saturation, ferritin, and C-reactive protein did not change these findings. Conclusion: Even in patients with kidney failure, G-3-P may rise in response to phosphate retention and act as a regulator of FGF23 production. Further studies are needed to test these hypotheses and determine whether the apparently nonfunctioning kidney retains the capacity to produce G-3-P.

Abstract Background It remains unclear which is more important for long-term secondary prevention of coronary artery disease (CAD), the glycemic control represented by the glycated hemoglobin (HbA1c) level or predominance of small dense LDL (sdLDL) that is a feature of diabetic dyslipidemia. Purpose This study was aimed to investigate how sdLDL cholesterol (sdLDL-C) and poor diabetic management could predict long-term CAD events in patients with stable CAD. Methods sdLDL-C measured using homogenous assay were evaluated in 744 male and 230 female patients with stable CAD who did not need urgent coronary revascularization. CAD events defined as sudden cardiac death, onset of acute coronary syndrome, and/or need for coronary revascularization were monitored for 12 years. According to receiver operating characteristic curves for CAD events, the most and the second most predictors were HbA1c and sdLDL-C, respectively. Cut-points of sdLDL-C were 32.1 mg/dL. Patients were classified into four groups based on HbA1c levels of 7.0% and sdLDL-C. Multivariable hazards model was used to examine the relationship between high HbA1c and high sdLDL-C for incident risk of CAD. Results HbA1c levels in 50% of 407 diabetic patients were above 6.9%. The first CAD events were observed in 238 male and 67 female patients. The Kaplan–Meier event-free survival curves showed that patients with either sdLDL-C ≥32.1 mg/dL or HbA1c ≥7.0% had an increased risk for CAD events. The multivariable-adjusted hazard ratios (HRs) were 1.901, 95% confidence interval (CI) 1.261-2.866 in patients with both high sdLDL-C and high HbA1c, These results were somewhat potentiated in 654 patients treated with lipid-lowering agents (HR 2.321, 95%CI 1.414-3.809 in patients with both high HbA1c and high sdLDL-C). Conclusions Combination of non-optimal diabetic control and high levels of sdLDL-C can predict long-term recurrence of CAD in stable CAD patients independently of other coronary risk factors.

We aimed to clarify the clinical characteristics and outcomes of patients with in-hospital onset ischemic stroke (IOS) compared with those in patients with community-onset ischemic stroke (COS). Patients from the Japan Stroke Data Bank, a hospital-based multicenter prospective registry, who were diagnosed with acute ischemic stroke (AIS) within 24 h of onset between January 2001 and December 2020 were included in this study. We assessed favorable outcomes at discharge corresponding to a modified Rankin Scale (mRS) score of 0-2, unfavorable outcomes corresponding to an mRS score of 5-6, and mortality. We also examined trends in these outcomes at 4-year intervals over a period of 20 years. Of the 100,865 patients analyzed, 2979 had IOS (1416 women, mean age 77 ± 12 years) and were older than those with COS (n = 97,886; 39,110 women, mean age 74 ± 12 years). Multivariate analysis revealed that younger age, higher premorbid mRS score, absence of stroke history, normotension, congestive heart failure, coronary artery disease, chronic kidney disease, liver disease, malignancy, tendency to bleed, and cardioembolic stroke were positively associated with IOS. Compared with COS, IOS was inversely associated with a favorable outcome (42.1% vs 64.8%, adjusted odds ratio [aOR] 0.72 [95% confidence interval (CI) 0.63-0.82]), positively associated with an unfavorable outcome (mRS 5-6 at discharge; 34.3% vs 15.5%, aOR 1.31 [95% CI 1.16-1.48]), and mortality (11.8% vs 4.6%, aOR 1.59 [95% CI 1.37-1.84]). Over 20 years, the mortality rate significantly decreased in both patients with IOS and COS (p < 0.01 both). IOS is associated with unfavorable outcomes and higher mortality rates during acute hospitalization. The mortality rates in patients with IOS decreased over time, similar to those observed in patients with COS.

A 66-year-old male patient underwent repair using the sutureless technique for an oozing-type cardiac rupture associated with myocardial infarction of the anterior left ventricular wall. On postoperative day 10, echocardiography revealed a thrombus in the apex region, and anticoagulation therapy was started with warfarin. The thrombus disappeared two months postoperatively. Four months after surgery, the patient came to the hospital with a chief complaint of breathlessness. The computer tomography scan showed a pseudoaneurysm in the left ventricular anterior wall. Because of breathlessness due to decreased effective cardiac output associated with the left ventricular mass and the risk of rupture of the left ventricular pseudoaneurysm, we decided that surgery was indicated. When the left ventricular pseudoaneurysm was incised under cardiac arrest using an artificial heart-lung machine, an oval-shaped communication orifice was found, which was closed directly with continuous sutures. The breathlessness disappeared and the patient was discharged 13 days after surgery.

Sampson et al. proposed a method to calculate small dense low-density lipoprotein-cholesterol (sdLDL-C) concentrations using common lipid measurements, but its accuracy remains unresolved. We examined the difference between Sampson's equation and direct measurement in patients with diabetes. sdLDL-C was measured directly by our established homogeneous assay and estimated by Sampson's equation in patients with diabetes (n=1542) and healthy control subjects (n=673). Large-buoyant (lb)LDL-C was estimated using triglycerides and LDL-C, and sdLDL-C was obtained by subtracting lbLDL-C from LDL-C. The effect of fasting/nonfasting state or lipid-lowering drug therapy on sdLDL-C values was also examined in 30 and 43 patients with diabetes, respectively. The coefficient of determination (R 2 ) between calculated sdLDL-C and direct measurement was 0.73 and 0.61 for healthy controls and patients with diabetes, respectively. The R2 between calculated sdLDL-C and nonHDL-C or apolipoprotein B was 0.64 and 0.65, respectively. Calculated sdLDL-C was 4-5 mg/dl or 17%-18% higher than the direct measurement. The lower the plasma lipids, especially sdLDL-C, the greater the dissociation between the two methods. Sampson sdLDL-C was also found to give a positive bias when calculated for the nonfasting samples. Statins and pemafibrate significantly reduced sdLDL-C, but their therapeutic effect was underestimated by 5 mg/dl (24%) via Sampson's equation. The correlation between Sampson's equation and direct measurements of sdLDL-C was reduced in patients with diabetes. Furthermore, the correlations with nonHDL-C and apolipoprotein B were even higher than those with direct sdLDL-C. The accuracy of Sampson's equation decreased with lower sdLDL-C concentrations and was also influenced by diet.

Higher heat flux than its normal criticality from high-power transistors, LIDAR (Laser Imaging Detection and Ranging), stacked CPUs, high-power transistors, and lasers must be efficiently transferred to cooling media through the metallic interface. The micro-/nano-textured aluminum and copper devices were highlighted among several approaches and fabricated to enhance the boiling heat transfer process to the subcooled water. The plasma printing was proposed to fabricate a pure aluminum device with concave micro-textures and to describe the boiling heat transfer behavior with comparison to the bare aluminum plate. A copper device was wet-plated to have convex micro-textures and to discuss the effect of micro-textures on the heat transfer characteristics under the forced water cooling by varying the Reynolds number. The boiling curve on the micro-textured interfaces was newly constructed by improving the boiling heat transfer process by micro-/nano-texturing.

The development of statins has significantly improved the prognosis of patients with coronary artery disease (CAD). Furthermore, the low-density lipoprotein (LDL)-cholesterol (C)-lowering effect of statins strongly suggests that LDL-C is the main cause of CAD. However, some patients have been reported to still develop CAD even after treatment with statin. Thus, the term "residual risk factor" has become a popular subject of discussion. Residual risk means a risk that cannot be reduced by statin therapy. It is also widely recognized as risk associated with hypertriglyceridemia and low high-density lipoprotein (HDL)-C. However, whether they really cause residual risk remains undetermined. Randomized Evaluation of Aggressive or Moderate Lipid-Lowering Therapy with Pitavastatin in Coronary Artery Disease (REAL-CAD) is a large-scale secondary intervention study, which was conducted to examine if the high-dose pitavastatin therapy (4 mg/dL) can reduce the risk of major adverse cardiovascular events (MACE) in patients with stable CAD compared with the low-dose pitavastatin therapy (1 mg/dL) 1) . The results indicated that high-intensity statin therapy was beneficial for CAD patients compared with low-intensity statin therapy. The switching from low to high doses of pitavastatin resulted in a further reduction in LDL-C. This study demonstrated a significant reduction in the occurrence of MACE in the high-dose statin group. However, it remains unclear whether the reduction was entirely due to a decrease in LDL-C and who the responder to high-dose pitavastatin is. In this issue of The Journal of Atherosclerosis and Thrombosis, Ishii et al 2) reported unexpected data in the REAL-CAD subanalysis that was conducted for a prospective casecohort substudy within the original REAL-CAD study. Their results indicated the need for further discussion on LDL-C to find out what the residual