Renal effects of sodium glucose co-transporter 2 inhibitors in Japanese type 2 diabetes mellitus patients with home blood pressure monitoring.

Decrease in blood pressure contributes to the reno-protective effects of sodium-glucose cotransporter 2 inhibitors; however, its relationship with home monitoring of blood pressure is unclear. We retrospectively analyzed 101 visiting members of the Kanagawa Physicians Association with type 2 diabetes mellitus and chronic kidney disease who were taking sodium-glucose cotransporter 2 inhibitors and who monitored blood pressure at home for a median treatment period of 14 months. At baseline, the mean value of HbA1c was 59.3 mmol/mol (7.6%) and the median value of albumin-creatinine ratio was 30.9 mg/gCr that was evaluated in 88 patients. The mean blood pressure both at office and home significantly decreased, and there was a significant positive correlation between the change in albumin-creatinine ratio and both blood pressures. Controlled hypertension, masked hypertension, white coat hypertension, and sustained hypertension were observed in 10.9%, 13.9%, 12.9%, and 62.4% of patients at the initiation of therapy, which changed to 10.9%, 16.8%, 17.8%, and 54.5% at the time of the survey, respectively. In conclusion, management of blood pressure both at office and home was found to be important for the reno-protective effects of sodium-glucose cotransporter 2 inhibitors along with strict blood pressure management.

Shape-Controlled Syntheses of Magnetite Microparticles and Their Magnetorheology.

Magnetic microspheres in a concentrated suspension can be self-assembled to form chain structures under a magnetic field, resulting in an enhanced viscosity and elasticity of the suspension (i.e., the magnetorheological (MR) effect). Recently, interest has been raised about the relationship between nonspherical particles, such as octahedral particles and the MR effect. However, experimental studies have not made much progress toward clarifying this issue due to the difficulty associated with synthesizing microparticles with well-defined shapes and sizes. Here, we presented a method for the shape-controlled synthesis of magnetite (Fe3O4) microparticles and investigated the MR effects of two suspensions prepared from the two shape-controlled samples of Fe3O4 microparticles. Our method, which was based on the polyol method, enabled the preparation of spherical and octahedral Fe3O4 microparticles with similar sizes and magnetic properties, through a reduction of α-FeOOH in a mixed solvent of ethylene glycol (a polyol) and water. The water played an important role in both the phase transition (α-FeOOH to Fe3O4) and the shape control. No substantial difference in the MR effect was observed between an octahedral-particle-based suspension and a spherical-particle-based one. Therefore, in this study, the shape of the microparticles did not strongly influence the MR effect, i.e., the properties of the chain structures.

A questionnaire survey of general practitioners in Japan's Kanagawa Prefecture for the Japanese Society of Hypertension Guidelines for the Management of Hypertension 2014.

To evaluate the Japanese Society of Hypertension Guidelines for the Management of Hypertension 2014 (JSH2014) among Japanese general practitioners (GPs), we used a questionnaire survey with 209 GPs from the Kanagawa Physicians Society. Overall, 93.6% of GPs felt that the contents of the JSH2014 were useful. Based on the results showing that 81.8% of GPs instructed the measurement of blood pressure (BP) in the early morning at home to most patients, GP's acceptance of home BP methods and their penetration among patients with hypertension were considerably high. Regarding the number of home BP measurements, percentages for "one time," "two times," "three times," and "as many times as the patient decides," were 20.2%, 44.9%, 12.2%, and 22.9%, respectively; as such, no consensus was reached. Overall, 80.6% of GPs instructed most patients on sodium restriction; however, the content and method of restriction varied. Furthermore, 14.7% collected spot urine to assess salt intake. Many GPs respected the JSH2014 and faithfully adopted the guidelines during medical care. However, GPs did not necessarily agree with all guidelines. GPs sometimes selected the appropriate method for the individual patients and careful observations of how the guidelines affect actual clinical practice may lead to better medical care.

Hydrothermal Synthesis of Yttria-Stabilized Zirconia Nanocrystals with Controlled Yttria Content.

In this study, we demonstrate for the first time the hydrothermal synthesis of yttria-stabilized zirconia (YSZ) nanocrystals with controlled yttria content (x = 3-12 mol %; xYSZ) with negligible aggregation from aqueous solution. The nanocrystals were grown via the hydrothermal treatment of basic Zr(IV) and Y(III) carbonate complex aqueous solutions in the presence of a cationic ligand, N(CH3)4(+). The nanocrystals were characterized in detail by dynamic light scattering, ζ-potential measurement, X-ray diffraction, specific surface area measurement based on the Brunauer-Emmett-Teller theory, transmission electron microscopy, energy dispersive X-ray spectroscopy, and Raman spectroscopy. Shorter reaction times and higher Y2O3 content produce aqueous solutions with higher transparencies containing nanocrystals with sizes of 10 nm or less. Nanocrystals with the target composition were obtained by hydrothermal reaction for longer than 3 h, regardless of the Y2O3 content. The main phase is tetragonal for (3-6)YSZ and cubic with disordered oxygen vacancies for (8-12)YSZ. The characteristics of the nanocrystalline material synthesized are consistent with those of bulk YSZ crystals, indicating the growth of high-quality nanocrystals.

Surface capping-assisted hydrothermal growth of gadolinium-doped CeO2 nanocrystals dispersible in aqueous solutions.

Nanocrystals of 20 mol % Gd(3+)-doped CeO2 dispersible in basic aqueous solutions were grown via hydrothermal treatment of anionic Ce(IV) and Gd(III) carbonate complexes at 125-150 °C for 6-24 h with N(CH3)4(+) as a capping agent. The nanocrystals were characterized in detail using dynamic light scattering (DLS), ζ-potential measurements, X-ray diffraction (XRD), specific surface area measurements based on the Brunauer-Emmett-Teller theory (SSA(BET)), transmission electron microscopy (TEM), energy dispersive X-ray spectroscopy, and Raman spectroscopy. DLS analysis revealed that the highly transparent product solution consisted of nanocrystals approximately 10-20 nm of hydrodynamic diameter with a very narrow size distribution, while the ζ-potential analysis results strongly suggested that the N(CH3)4(+) capped negatively charged sites on the nanocrystals' surface and provided sufficient repulsive steric effect to prevent agglomeration. Moreover, the crystallite size (d(XRD)) estimated from the XRD patterns and the equivalent particle size (d(BET)) estimated from the SSA(BET) data were in the range between 5-6 and 4-4.5 nm, respectively, and nearly constant independent of reaction time, indicating suppressed Ostwald ripening due to capping. Good agreement between the values obtained from the d(XRD) and d(BET) analyses with the size of the primary nanocrystals observed in the TEM image also confirmed that the primary nanocrystals were single crystals and nearly free from aggregation. Furthermore, the gadolinium content in the as-prepared nanocrystals was determined to be very close to 20 mol % and remained unchanged after HCl treatment, indicating successful doping of stoichiometric amount of Gd(3+) into CeO2 lattices. Finally, the Raman analysis suggested that only a slightly Gd(3+)-rich phase was present in the nanocrystals grown for shorter reaction times. By increasing the reaction time, even at 125 °C, the Gd(3+) was homogeneously distributed into the CeO2 lattices via solid state diffusion.

Pretreatment body mass index affects achievement of target blood pressure with sodium-glucose cotransporter 2 inhibitors in patients with type 2 diabetes mellitus and chronic kidney disease.

Sodium-glucose cotransporter 2 inhibitor (SGLT2-I) shows excellent antihypertensive effects in addition to its hypoglycemic effects. However, whether body mass index (BMI) affects the antihypertensive effect of SGLT2-I remains unknown. We investigated the impact of baseline BMI on the achievement of target blood pressure (BP) with SGLT2-I treatment in Japanese patients with type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD). We retrospectively evaluated 447 Japanese patients with T2DM and CKD treated with SGLT2-I for at least 1 year. The primary outcome was achieving the target BP (<130/80 mmHg) after SGLT2-I treatment. Patients were divided into two groups according to a baseline BMI of 29.1 determined by receiver operating characteristic analysis and analyzed in a cohort model with propensity score matching. In each group, 130 patients were compared by propensity score matching. The target BP achievement rate was significantly higher in the BMI < 29.1 group than in the BMI ≥ 29.1 group (34% and 21%, respectively, p = 0.03). The odds ratio for achieving the target BP in the BMI ≥ 29.1 group was 0.50 (95% confidence interval, 0.28-0.90, p = 0.02). The BMI < 29.1 group had significantly lower systolic and diastolic BPs after SGLT2-I treatment than the BMI ≥ 29.1 group. Only the BMI < 29.1 group was showed a significant decrease in the logarithmic albumin-to-creatinine ratio from baseline after SGLT2-I treatment. In patients with T2DM and CKD, baseline BMI was associated with the antihypertensive effects of SGLT2-I. Patients in the lower baseline BMI group were more likely to achieve the target BP after SGLT2-I treatment. Pretreatment BMI affects the antihypertensice effect of SGLT2 inhibirors in patients with T2DM and CKD.

Defective multi-element hydroxides nanosheets for rapid removal of anionic organic dyes from water and oxygen evolution reaction.

Water pollution by dyes is one of the biggest environmental problems. Adsorption technology has been widely used in wastewater treatment. In this work, high-entropy concept is used to design surface defective hydroxides realizing the rapid removal of dyes from water. Multi-element hydroxides (MEHs) containing three (CoMnNi, MEH-Ternary), four (CoMnNiZn, MEH-Quaternary), and five (CoMnNiZnFe, MEH-Quinary) metal elements are successfully synthesized through a polyol process. These as-synthesized MEHs are composed of nanosheets with a brucite-like structure. Along with the increase in compositional complexity (i.e., configurational entropy), the thickness of the nanosheets in these MEHs decreases, while the degree of surface defects increase. These surface defects are probably the active sites for anionic dyes adsorption, suggesting rapid adsorption kinetics with shortened diffusion path length. For MEH-Quinary in 0.2 mM Congo red (CR) and MEH-Ternary in 0.4 mM methyl orange (MO) aqueous solutions, respectively, high removal efficiency > 99.0% is achieved in the first 30 s. Their pseudo-second-order rate constants are two orders of magnitude higher than that of activated carbon and hydrotalcite. MEH-Quinary has maximum CR and MO adsorption quantity of 546.4 and 404.9 mg g-1, respectively, by Langmuir model. The MEH-Quinary is also a potential electrocatalyst for oxygen evolution reaction.

Primary cardiac myxofibrosarcoma of the left atrium and pericardium: a case report.

BACKGROUND: Primary cardiac myxofibrosarcoma is rare and commonly occurs in the left atrium. Myxofibrosarcoma is aggressive and has a high mortality rate due to its high rate of recurrence. Complete surgical resection is considered important; however, effective treatment options have not been established. CASE PRESENTATION: We report the case of a 75-year-old woman who developed a myxofibrosarcoma spreading to the left atrium and pericardium. We performed surgical resection of the tumor to prevent sudden death due to mitral valve obstruction or cerebral infarction due to embolism of the scattered mass. However, we were unable to complete the resection of the tumors. The patient developed brain metastasis 2 months after surgery and eventually died due to brain hemorrhage 3 months after surgery. CONCLUSIONS: In this report, we described a rare case of primary cardiac myxofibrosarcoma located not only in the left atrium but also in the pericardium. Considering preoperative laboratory findings, surgical and adjuvant therapy, and the patient's wishes are important for the best therapeutic course for an individual.

Cross-sectional survey of hypertension management in clinical practice in Japan: the Kanagawa Hypertension Study 2021 conducted in collaboration with Japan Medical Association Database of Clinical Medicine.

We aim to assess the data of patients with hypertension in Kanagawa Prefecture, Japan, collected in 2021 that were provided by the Japan Medical Association Database of Clinical Medicine. Data collected in 2011 and 2014 by the Kanagawa Physicians Association were used for comparative analysis. The target blood pressure (BP) achievement rates for patients whose target office and home BP were <140/90 mmHg and <135/85 mmHg, respectively, were 72.5% and 75.8% in 2011, 66.0% and 68.5% in 2014, and 46.7% and 83.3% in 2021, respectively. The target office BP achievement rate in 2021 was significantly lower than those in 2011 and 2014 (p ≤ 0.009). In contrast, there was no significant difference and improvement of the achievement rates for patients whose target office and home BP were <130/80 mmHg and <125/75 mmHg, respectively, among the three surveys. After the Japanese Society of Hypertension 2019 Guidelines were released, the achievement rates for patients whose target BP was tightened were significantly lower than those for patients with unchanged target BP (office/home, p < 0.001/0.04). The proportion of the patients who achieved their office and home target BP using more than three drugs was 38.5% and 20.0%, respectively. In the present analysis, we unveiled the current problems encountered in the clinical management of hypertension in Japan. In particular, efforts should be focused on the management of patients that require strict BP control.

The concomitant use of sodium-glucose co-transporter 2 inhibitors improved the renal outcome of Japanese patients with type 2 diabetes treated with glucagon-like peptide 1 receptor agonists.

Aims: This study aimed to clarify the renal influence of glucagon-like peptide 1 receptor agonists (GLP1Ras) with or without sodium-glucose co-transporter 2 inhibitors (SGLT2is) on Japanese patients with type 2 diabetes mellitus (T2DM). Methods: We retrospectively extracted 547 patients with T2DM who visited the clinics of members of Kanagawa Physicians Association. The progression of albuminuria status and/or a ≥ 15% decrease in the estimated glomerular filtration rate (eGFR) per year was set as the renal composite outcome. Propensity score matching was performed to compare GLP1Ra-treated patients with and without SGLT2i. Results: After matching, 186 patients in each group were compared. There was no significant difference of the incidence of the renal composite outcomes (17% vs. 20%, P = 0.50); however, the annual decrease in the eGFR was significantly smaller and the decrease in the urine albumin-to-creatinine ratio was larger in GLP1Ra-treated patients with the concomitant use of SGLT2is than in those without it (-1.1 ±â€…5.0 vs. -2.8 ±â€…5.1 mL/min/1.73 m2, P = 0.001; and -0.08 ±â€…0.61 vs. 0.05 ±â€…0.52, P = 0.03, respectively). Conclusion: The concomitant use of SGLT2i with GLP1Ra improved the annual decrease in the eGFR and the urine albumin-to-creatinine ratio in Japanese patients with T2DM.

Concomitant treatment with insulin and sodium-glucose cotransporter 2 inhibitors was associated with the renal composite outcome in Japanese patients with type 2 diabetes and chronic kidney disease: A propensity score-matched analysis.

AIMS/INTRODUCTION: We previously reported that sodium-glucose cotransporter 2 inhibitor (SGLT2i) treatment was associated with an improvement of the albumin-to-creatinine ratio in Japanese patients with type 2 diabetes mellitus and chronic kidney disease. The present study clarified how concomitant insulin treatment (IT) with SGLT2i therapy influences the renal composite outcome (RCO). MATERIALS AND METHODS: We retrospectively evaluated 624 Japanese patients with type 2 diabetes mellitus and chronic kidney disease who underwent SGLT2i treatment. The renal composite outcome was set as progression of the stage of albuminuria or a ≥15% decrease in the estimated glomerular filtration rate per year. We developed a cohort model of patients managed with and without IT (Ins [+], Ins [-]) using propensity score matching methods. Furthermore, all patients in our study population were stratified into quintiles according to their propensity score. RESULTS: The incidence of the RCO was in Ins (+) patients significantly higher than that in Ins (-) (P = 0.033). The estimated hazard ratio for the RCO was 1.55 (P = 0.035) in Ins (+) patients. The change in the estimated glomerular filtration rate and albumin-to-creatinine ratio in the groups was not statistically significant. The analysis, which was based on the quintiles, showed a statistically significant difference between the Ins (+) and Ins (-) groups (P = 0.01); the odds ratio for the RCO in patients managed with IT was 2.20 (P = 0.01). CONCLUSIONS: Concomitant administration of IT with SGLT2is influenced the RCO in Japanese patients with type 2 diabetes mellitus and chronic kidney disease. We might need to consider the influence of concomitant agents on the renoprotective effects of SGLT2i therapy.

Polypharmacy influences the renal composite outcome in patients treated with sodium-glucose cotransporter 2 inhibitors.

Polypharmacy is a serious concern in general practice, especially among elder patients; however, the evidence showing significantly poor renal outcomes is not sufficient. This survey was performed to evaluate the effect of polypharmacy on the incidence of the renal composite outcome among a sample of patients with sodium-glucose cotransporter 2 inhibitor (SGLT2i) treatment. We assessed 624 Japanese patients with type 2 diabetes mellitus (T2DM) and chronic kidney disease who received SGLT2i treatment for greater than 1 year. The patients were classified as those with concomitant treatment, that was limited to the medications for hypertension, T2DM, and dyslipidemia, with greater than or equal to seven medications (n = 110) and those with less than seven medications (n = 514). Evaluation of the renal composite outcome was performed by propensity score matching and stratification into quintiles. A subgroup analysis of patients of greater than or equal to 62 years of age and less than 62 years of age was also performed. The incidence of the renal composite outcome was larger in patients with greater than or equal to seven medications than in those with less than seven medications in the propensity score-matched cohort model (6% vs. 17%, respectively, p = 0.007) and also in the quintile-stratified analysis (odds ratio [OR], 2.23, 95% confidence interval [CI, 1.21-4.12, p = 0.01). The quintile-stratified analysis of patients of less than 62 years of age-but not those of greater than or equal to 62 years of age-also showed a significant difference (OR, 3.29, 95% CI, 1.41-7.69, p = 0.006). Polypharmacy appears to be associated to the incidence of the renal composite outcome, especially in young patients.

Comparison of the blood pressure management between sodium-glucose cotransporter 2 inhibitors and glucagon-like peptide 1 receptor agonists.

The cardiovascular and renal protective effects of sodium-glucose cotransporter 2 inhibitors (SGLT-2is) and glucagon-like peptide 1 receptor agonists (GLP-1Ras) are enhanced by low/controlled blood pressure (BP). However, the BP-lowering efficacy of SGLT-2is and GLP-1Ras have not been compared directly. We compared the rates of achieving target BP with SGLT-2i and GLP-1Ra treatments in Japanese patients with type 2 diabetes mellitus (T2DM). This retrospective study included 384 SGLT-2i- and 160 GLP-1Ra-treated patients with BP > 130/80 mmHg before treatment. Inverse probability weighting methods using propensity scores were used in this study. The integrated odds ratios (OR) for BP control rates were calculated and clinical changes were analyzed using a generalized linear model. SGLT-2i treatment resulted in significantly higher BP control rates than that in the GLP-1Ra treatment (integrated OR = 2.09 [1.80, 2.43]). Compared with GLP-1Ra, SGLT-2i treatment demonstrated significantly larger decreases in diastolic BP, mean arterial pressure, and body weight (- 3.8 mmHg, P = 0.006; - 4.1 mmHg, P = 0.01; and - 1.5 kg, P = 0.008, respectively) and increased annual estimated glomerular filtration rate (eGFR; 1.5 mL/min/1.73 m2/year, P = 0.04). In T2DM patients with poorly controlled BP, compared with GLP-1Ra, SGLT-2i treatment significantly improved BP management and increased eGFR.

Comparison of renal outcomes between sodium glucose co-transporter 2 inhibitors and glucagon-like peptide 1 receptor agonists.

AIMS: This study aimed to clarify the differences in how sodium glucose co-transporter 2 inhibitors (SGLT2i) and glucagon-like peptide 1 receptor agonists (GLP1Ra) influence kidney function in Japanese patients with type 2 diabetes mellitus (T2DM). METHODS: We retrospectively built two databases of patients with T2DM who visited the clinics of members of Kanagawa Physicians Association. We defined the renal composite outcome as either progression of albuminuria status and/or > 15% deterioration in estimated glomerular filtration rate (eGFR) per year. We used propensity score matching to compare patient outcomes after SGLT2i and GLP1Ra treatments. RESULTS: The incidence of renal composite outcomes was significantly lower in SGLT2i-treated patients than in GLP1Ra-treated patients (n = 15[11%] and n = 27[20%], respectively, P = 0.001). Annual eGFR changes (mL/min/1.73 m2/year) between the two groups differed significantly (-1.8 [95 %CI, -2.7, -0.9] in SGLT2i-treated patients and - 3.4 [95 %CI, -4.6, -2.2] in GLP1Ra-treated patients, P = 0.0049). The urine albumin-to-creatinine ratio changed owing to a significant interaction between the presence or absence of a decrease in systolic blood pressure and the difference in treatments (P < 0.04). CONCLUSION: Renal composite outcome incidence was lower in SGLT2i-treated patients than in GLP1Ra-treated patients.

The Comparison of the Kidney Effects of Dipeptidyl Peptidase 4 Inhibitors and Glucagon-Like Peptide 1 Agonist-Administered Concomitant with Sodium-Glucose Cotransporter 2 Inhibitors in Japanese Patients with Type 2 Diabetes Mellitus and Chronic Kidney Disease.

METHODS: We retrospectively constructed database of 763 Japanese patients with T2DM and CKD who received sSGLT2is for more than 1 year. Among these SGLT2i-treated patients, 338 were receiving concomitant DPP4i (DPP4i group), and 99 were receiving concomitant GLP1Ra (GLP1Ra group). The two groups were compared using the propensity score matching method. RESULTS: In the matched model including 86 cases per group, the decrease in the logarithmic value of the ACR and rate of reduction in the estimated glomerular filtration rate (eGFR; mL/min/1.73 m2) of the GLP1Ra group showed no significant difference from those in the DPP4i group (-0.12 ± 0.48 vs. -0.13 ± 0.45 and -2.3 ± 18.5 vs. -6.2 ± 13.8, respectively, P = 0.10). However, the incidence of a >6.4% decrease in the eGFR was significantly lower in the GLP1Ra group than in the DPP4i group (35% vs. 52%, respectively, P = 0.03). The level of hemoglobin A1c (mmol/mol) after SGLT2i treatment was significantly lower in the DPP4i group than in the GLP1Ra group in the matched model (58.3 ± 11.8 and 62.7 ± 14.8, respectively, P = 0.02). CONCLUSION: Among the SGLT2i-treated patients with T2DM and CKD, concomitant treatment with GLP1Ra has a marked improving effect on the change in the eGFR.

The evaluation of noninferiority for renal composite outcomes between sodium-glucose cotransporter inhibitors in Japan.

BACKGROUND: In Japan, six types of sodium-glucose cotransporter inhibitors (SGLT2Is) are currently in use. Here, we evaluated differences in renal composite outcomes between SGLT2Is with or without evidence of cardio vascular outcome trials (CVOTs). METHODS: We retrospectively surveyed 536 Japanese patients with type 2 diabetes mellitus with chronic kidney disease who received SGLT2Is for more than 1 year. Patients were classified as having received empagliflozin, canagliflozin, or dapagliflozin (n = 270, Evidence (+) group) or as having received ipragliflozin, tofogliflozin, or luseogliflozin (n = 266, Evidence (-) group). The propensity score matching method was performed. RESULT: On matched cohort model including 205 cases in each group, there were no significant differences in the incidence of renal composite outcomes (n = 28 [14%] in the Evidence (+) group, n = 21 [10%] in the Evidence (-) group for the matched model; p = 0.29) between groups. Cox hazard analyses in the matched cohort model showed that the risk ratio for renal composite outcomes in the Evidence (-) group was 0.73 (95% confidence interval: 0.40-1.32), which was greater than the noninferiority margin of 1.22. CONCLUSION: Three SGLT2Is with no CVOT's evidence did not show noninferiority compared with other SGLT2Is with evidences.

Sodium-glucose cotransporter 2 inhibitor-induced reduction in the mean arterial pressure improved renal composite outcomes in type 2 diabetes mellitus patients with chronic kidney disease: A propensity score-matched model analysis in Japan.

AIMS/INTRODUCTION: Large-scale clinical trials have reported that, in patients with type 2 diabetes mellitus, sodium-glucose cotransporter 2 (SGLT2) inhibitor treatment affords favorable renal outcomes; the underlying mechanisms, however, remain unclear. Thus, this study investigated how SGLT2 inhibitor-induced changes in the mean arterial pressure (MAP; denoted as ΔMAP) are associated with renal outcomes in type 2 diabetes mellitus patients with chronic kidney disease (CKD). MATERIALS AND METHODS: We retrospectively assessed the data of 624 Japanese type 2 diabetes mellitus patients with CKD who had been using SGLT2 inhibitors for >1 year. For propensity score matching (1:1 nearest neighbor match, with caliper value = 0.053, no replacement), patients were categorized into two groups based on the ΔMAP (>-4 mmHg [n = 329] and ≤-4.0 mmHg [n = 295]). Composite albuminuria progression or a ≥15% annual reduction in the estimated glomerular filtration rate was regarded as the end-point. RESULTS: Per group, 173 propensity-matched patients were compared. Patients with ΔMAP ≤-4 mmHg had a significantly lower incidence of composite renal outcomes than those with ΔMAP ≥-4 mmHg (5.8% [n = 10] vs 15.6% [n = 27], P = 0.003). Although the between-group differences in the estimated glomerular filtration rates were non-significant, patients with a ΔMAP ≤-4 mmHg had significantly larger reductions in the logarithmic urine albumin-to-creatinine ratio (P = 0.005). CONCLUSIONS: The degree of blood pressure reduction after SGLT2 inhibitor treatment influenced renal composite outcomes in Japanese type 2 diabetes mellitus patients with CKD, confirming the importance of blood pressure management in type 2 diabetes mellitus patients with CKD, even when they are under SGLT2 inhibitor treatment.

Comparison of questionnaire responses regarding awareness of Japanese Society of Hypertension guidelines for the management of hypertension between 2014 and 2019 in primary care.

In 2019, the Japanese Society of Hypertension guidelines for the management of hypertension (JSH) were revised. We previously reported the awareness of JSH among general practitioners in 2014, and in the current study, the same questionnaire was administered to determine their awareness of JSH 2019, and their responses were compared. We also sought to identify effective strategies to raise awareness of hypertension. The questionnaires included the same 12 questions as in 2014 and were mailed to members of two professional organizations from October to November 2019. Responses from 256 general practitioners in 2019 and 209 in 2014 were compared using the propensity score matching method to align the responders' backgrounds. Component analysis was performed to classify responders into appropriate clusters. The matched cohort of all 202 responders was analyzed. In both 2014 and 2019, >80% of responders instructed patients to perform home blood pressure monitoring (JSH 2014: 81.7% and JSH 2019: 84.6% in the matched cohort), and >70% instructed patients with hypertension to restrict their salt intake (JSH 2014: 79.7% and JSH 2019: 74.7% in the matched cohort). Regarding the clinical blood pressure measurement method, more responders answered "one time outside the consulting room" in the JSH 2019 group (p = 0.042). Fewer general practitioners responded that differential diagnosis for primary aldosteronism was performed in the JSH 2019 group (p = 0.032); however, the frequency of checking the aldosterone-renin ratio increased in the JSH 2019 group (p = 0.055). We confirmed the change in general practitioners' awareness of hypertension management. The categorized clusters may be useful for the development of effective strategies for higher-quality hypertension management in clinical practice.

Titanium oxide nano-radiosensitizers for hydrogen peroxide delivery into cancer cells.

Polyacrylic acid-modified titanium peroxide nanoparticles (PAA-TiOx NPs) are promising radiosensitizers that enhance the therapeutic effect of X-ray irradiation after local injection into tumors. However, the mechanism for this reaction has remained unclear with the exception of the involvement of hydrogen peroxide (H2O2), which is released by PAA-TiOx NPs to a liquid phase during dispersion. In the present study, a clonogenic assay was used to compare PAA-TiOx NPs with free H2O2 molecules to investigate the effect exerted on the radiosensitivity of cancer cells in vitro. A cell-free dialysis method revealed that a portion of the H2O2 adsorbed onto the PAA-TiOx NPs during synthesis could be released during a treatment regimen. The H2O2 release lasted for 7 h, which was sufficient for one radiation treatment procedure. For in vitro experiments, cultured human pancreatic cancer cells took up PAA-TiOx NPs in 10 min after administration. Interestingly, when the cells were washed with a buffer after treatment with either a PAA-TiOx NP or H2O2 solution, the intracellular H2O2 levels remained higher with PAA-TiOx NP treatment compared with the H2O2 solution treatment. Furthermore, the effects of subsequent X-ray irradiation corresponded to the intracellular H2O2 levels. These results indicate that PAA-TiOx NPs are efficient carriers of H2O2 into cancer cells and thus enhance the radiosensitivity.

Outcomes of Patients Who Undergo Transfusion of Fresh Frozen Plasma: A Prospective, Observational, Multicentre Cohort Study in Hiroshima, Japan.

PURPOSE: Given the chronic shortage of blood for transfusion in Japan, promotion of appropriate use of fresh frozen plasma (FFP) urgently needs to be addressed by the national blood project in Japan. Whether FFP transfusions are administered appropriately in Japan is currently unclear. In this study, we aimed to investigate the outcomes of patients who undergo FFP transfusion and the appropriateness of use of FFP. PATIENTS AND METHODS: This multicentre, prospective, observational cohort study was conducted from September 2017 to April 2019 at the 15 medical institutions in Hiroshima Prefecture that are the top providers of FFP. All patients who underwent FFP transfusion during the study period were included, relevant data being extracted from the medical records. The indications for FFP transfusion were classified in accordance with the Guidelines of the Ministry of Health, Labour and Welfare of Japan. Factors associated with patient outcomes at day 28 after FFP transfusion were subjected to multivariable logistic regression analysis. RESULTS: In total, data of 1299 patients were eligible for analysis. At least 63.8% of indications for FFP were in accordance with the guideline for FFP transfusions. The mortality rate at day 28 after FFP transfusion was 16.2%. Older age (65-74 years: adjusted odds ratio [AOR]=4.3, ≥75 years: AOR=4.1), non-perioperative use (AOR=4.5), coagulopathy associated with liver damage (AOR=2.7), large volume of FFP transfused (AOR=2.5), and lack of improvement in blood coagulation following FFP transfusion were independently and significantly associated with death within 28 days after FFP transfusion. CONCLUSION: Our findings do not support the simple conclusion that FFP transfusions contribute to prognosis. However, given that coagulopathy in patients with end-stage liver disease is infrequently improved by FFP transfusion, "inappropriate" use of FFP should be avoided. It is important to promote appropriate use of FFP so as not to waste blood resources.