Effectiveness of digital health interventions for telemedicine/telehealth for managing blood pressure in adults: a systematic review and meta-analysis.

This systematic review and meta-analysis included randomized controlled trials or observational studies that compare digital health interventions (DHIs) for telemedicine/telehealth versus usual care for managing blood pressure (BP) in adults. We searched PubMed, Cochrane CENTRAL, and IchuShi-Web, and used a random-effects meta-analysis of the weighted mean difference (MD) between the comparison groups to pool data from the included studies. The outcome included the pooled MD of office BP from baseline to each follow-up period. This meta-analysis considered 117 studies with 68677 participants as eligible. The 3-month intervention period reduced office systolic BP (SBP) compared with usual care in 38 studies (MD: -3.21 mmHg [95% confidence interval: -4.51 to -1.90]), with evidence of heterogeneity. Office SBP across intervention periods demonstrated comparable effects (3-, 6- [54 studies], 12- [43 studies], and >12-month periods [9 studies]). The benefits for office diastolic BP were similar to those for office SBP. Additionally, the interventions significantly reduced the office SBP compared with the control, regardless of the mode of intervention delivery (smartphone apps [38 studies], text messages [35 studies], and websites [34 studies]) or type of facility (medical [74 studies] vs. non-medical [33 studies]). The interventions were more effective in 41 hypertension cohorts compared with 66 non-hypertension cohorts (-4.81 mmHg [-6.33, -3.29] vs. -2.17 mmHg [-3.15, -1.19], P = 0.006 for heterogeneity). In conclusion, DHIs for telemedicine/telehealth improved BP management compared with usual care. The effectiveness with heterogeneity should be considered, as prudent for implementing evidence-based medicine. This meta-analysis considered 117 studies with 68677 participants eligible. The DHIs for telemedicine/telehealth reduced office BP compared with usual care, regardless of intervention duration, intervention delivery mode, facility type, and cohort type. Additionally, the DHIs reduced the risk of uncontrolled BP compared with usual care, regardless of intervention duration, intervention delivery mode, and facility type. BP blood pressure, DHI digital health intervention, MD mean difference, RR risk ratio, SBP systolic blood pressure.

Favorable changes in the eGFR slope after dapagliflozin treatment and its association with the initial dip.

BACKGROUND: Renoprotective effects of sodium glucose transporter 2 (SGLT2) inhibitors, including dapagliflozin, were observed in randomized controlled trials (RCTs). The suspected underlying mechanism is a correction of hyperfiltration, observed as an "initial dip". Whether SGLT2 inhibitors can attenuate the rate of decline in the estimated glomerular filtration rate (eGFR) in clinical settings, even when considering the pre-treatment decline rate, is unknown. Although several RCTs identified an association between the initial dip and long-term renal prognoses, a conclusion has not been reached. METHODS: We collected the eGFR data of patients for whom dapagliflozin was initiated in our hospital and then calculated their eGFR slopes before and after the start of the treatment. We investigated the changes in the eGFR slopes (ΔeGFR slope) and the association between the ΔeGFR slope and the initial dip. Risks for rapid eGFR decliners (eGFR slope < - 3 mL/min/1.73 m2/year) were also examined. RESULTS: The eGFR slope was significantly milder after dapagliflozin treatment (p < 0.01). A deeper initial dip was associated with a milder rate of eGFR decline (adjusted beta: - 0.29, p < 0.001). Dapagliflozin treatment reduced the proportion of rapid eGFR decliners from 52.9 to 14.7%, and a smaller initial dip was identified as a significant risk for post-treatment rapid eGFR decline (adjusted odds ratio: 1.73, p < 0.05). CONCLUSIONS: Compared to before the administration of dapagliflozin, the rate of eGFR decline was significantly milder after its administration. The initial dip was significantly associated with long-term renoprotective effects and may be a useful predictor of treatment response.

Early, Intensive and Persistent Lipid-Lowering Therapy for Secondary Prevention of Acute Coronary Syndrome.

AIM: Early and intensive low-density lipoprotein (LDL-C)-lowering therapy plays important roles in secondary prevention of acute coronary syndrome (ACS), but the treatment period for further clinical benefit remains undefined. This single-center, retrospective study explored LDL-C trajectory after ACS and its associations with subsequent cardiovascular events (CVE). METHODS: In 831 patients with ACS, we evaluated LDL-C reduction during the first 2 months post-ACS as an index of early intervention and the area over the curve for LDL-C using 70 mg/dl as the threshold in the next 6 months (AOC-70) as a persistent intensity index. Patients were followed for a median of 3.0 (1.1-5.2) years for CVE, defined as the composite of cardiovascular death, non-fatal myocardial infarction, angina pectoris requiring revascularization, cerebral infarction, and coronary bypass grafting. RESULTS: LDL-C decreased from baseline to 2 months post-ACS (107±38 mg/dl to 78±25 mg/dl, p＜0.001) through high-intensity statin prescription (91.8%), while achieving rates of LDL-C ＜70 mg/dl at 2 months remained only 40.2% with no significant changes thereafter. During the follow-up period, CVE occurred in 200 patients. LDL-C reduction during the first 2 months and AOC-70 in the next 6 months were both associated with subsequent CVE risk (sub-HR [hazard ratio] [95% confidence interval]: 1.48 [1.16-1.89] and 1.22 [1.05-1.44]). Furthermore, early intervention followed by persistently intensive LDL-C-lowering therapy resulted in further CVE risk reduction. CONCLUSIONS: The present study observed that achieving early and intensive LDL-C reduction within the first two months after ACS and maintaining it for the next six months suppressed subsequent CVE risk, suggesting the importance of early, intensive, and persistent LDL-C-lowering therapy in the secondary prevention of ACS.

Impact of compliance with salt management guidelines before dialysis introduction on peritoneal dialysis technique survival: The importance of pre-dialysis care and education.

INTRODUCTION: Peritoneal dialysis (PD) is a mode of therapy in which the patients themselves actively participate in the care of their own disease. We examined a possible association of salt reduction before starting dialysis with PD technique survival. METHODS: This retrospective cohort study included 42 patients who started PD between April 2014 and March 2018. Participants were allocated to two groups based on their estimated daily salt intake before the initiation of dialysis: patients with an estimated daily salt intake <6 g/day were allocated to the appropriate salt intake group (AS group), while the rest were assigned to the high salt intake group (HS group). RESULTS: During a median follow-up of 47 months, PD technique survival, defined by death or transition to hemodialysis, was significantly lower in the HS group compared to the AS group. CONCLUSION: Successful salt reduction before dialysis introduction is associated with better PD technique survival.

ATP2B1 gene polymorphisms associated with resistant hypertension in the Japanese population.

Single-nucleotide polymorphisms (SNP) of ATP2B1 gene are associated with essential hypertension but their association with resistant hypertension (RHT) remains unexplored. The authors examined the relationship between ATP2B1 SNPs and RHT by genotyping 12 SNPs in ATP2B1 gene of 1124 Japanese individuals with lifestyle-related diseases. Patients with RHT had inadequate blood pressure (BP) control using three antihypertensive drugs or used ≥4 antihypertensive drugs. Patients with controlled hypertension had BP controlled using ≤3 antihypertensive drugs. The association between each SNP and RHT was analyzed by logistic regression. The final cohort had 888 (79.0%) and 43 (3.8%) patients with controlled hypertension and RHT, respectively. Compared with patients homozygous for the minor allele of each SNP in ATP2B1, a significantly higher number of patients carrying the major allele at 10 SNPs exhibited RHT (most significant at rs1401982: 5.8% vs. 0.8%, p = .014; least significant at rs11105378: 5.7% vs. 0.9%, p = .035; most nonsignificant at rs12817819: 5.1% vs. 10%, p = .413). After multivariate adjustment for age, sex, systolic BP, and other confounders, the association remained significant for rs2681472 and rs1401982 (OR: 7.60, p < .05 and OR: 7.62, p = .049, respectively). Additionally, rs2681472 and rs1401982 were in linkage disequilibrium with rs11105378. This study identified two ATP2B1 SNPs associated with RHT in the Japanese population. rs1401982 was most closely associated with RHT, and major allele carriers of rs1401982 required significantly more antihypertensive medications. Analysis of ATP2B1 SNPs in patients with hypertension can help in early prediction of RHT and identification of high-risk patients who are more likely to require more antihypertensive medications.

Network Meta-Analysis of C5 Palsy After Anterior Cervical Decompression of Three to Six Levels: Comparing Three Different Procedures.

STUDY DESIGN: Systematic review and meta-analysis. OBJECTIVE: Using a network meta-analysis (NMA), this study aimed to compare the risks of C5 palsy after three different procedures of anterior cervical decompression. SUMMARY OF BACKGROUND DATA: C5 palsy is a well-known complication affecting the quality of life after anterior procedures. Due to the limited evidence on the various procedures available, we evaluate the basis for selection to prevent palsy and achieve maximal decompression in cases spanning 3-6 levels. MATERIALS AND METHODS: We conducted a comprehensive search for C5 palsy and complications after 3representative procedures, including anterior cervical discectomy and fusion (ACDF), anterior cervical corpectomy and fusion (ACCF), and their combination (hybrid), involving 3 to 6 intervertebral levels. The incidence of C5 palsy was compared using a NMA. RESULTS: We identified 1655 patients in 11 studies who met inclusion criteria. Sixty-nine patients (4.2%) developed delayed C5 palsies. The incidences among ACDF, ACCF, and hybrid cases were 2.3% (16/684, 95% CI: 1.4% to 3.8%), 6.4% (39/613, 95% CI: 4.7% to 8.6%), and 3.9% (14/358, 95% CI: 2.3% to 6.5%), respectively ( P < 0.01). A NMA was performed for 15 pairwise comparisons across the 3 procedure arms: ACDF versus hybrid, 7/232 (3.0%) versus 11/234 (4.7%); hybrid versus ACCF, 14/301 (4.3%) versus 18/224 (8.0%); ACCF versus ACDF, 38/523 (7.8%) versus 16/619 (2.6%). Compared with ACDF, the risk of C5 palsy was significantly higher in ACCF (odds ratio: 2.72, 95% CI: 1.47 to 5.01), whereas ACDF versus hybrid did not significantly differ in risk (odds ratio: 1.56, 95% CI: 0.68 to 3.60). CONCLUSION: We determined that ACCF was associated with a higher risk of postoperative C5 palsy than ACDF in cases spanning 3 to 6 intervertebral levels. If practicable, ACDF surgery may be an appropriate choice for cases requiring anterior decompression of 3 to 6 levels. LEVEL OF EVIDENCE: Level III.

Influence on the accuracy in ChatGPT: Differences in the amount of information per medical field.

OBJECTIVES: Although ChatGPT was not developed for medical use, there is growing interest in its use in medical fields. Understanding its capabilities and precautions for its use in the medical field is an urgent matter. We hypothesized that differences in the amounts of information published in different medical fields would be proportionate to the amounts of training ChatGPT receives in those fields, and hence its accuracy in providing answers. STUDY DESIGN: A non-clinical experimental study. METHODS: We administered the Japanese National Medical Examination to GPT-3.5 and GPT-4 to examine the rates of accuracy and consistency in their responses. We counted the total number of documents in the Web of Science Core Collection per medical field and assessed the relationship with ChatGPT's accuracy. We also performed multivariate-adjusted models to investigate the risk factors for incorrect answers. RESULTS: For GPT-4, we confirmed an accuracy rate of 81.0 % and a consistency rate of 88.8 % on the exam; both showed improvement compared to those for GPT-3.5. A positive correlation was observed between the accuracy rate and consistency rate (R = 0.51, P < 0.001). The number of documents per medical field was significantly correlated with the accuracy rate in that medical field (R = 0.44, P < 0.05), with relatively few publications being an independent risk factor for incorrect answers. CONCLUSIONS: Checking consistency may help identify incorrect answers when using ChatGPT. Users should be aware that the accuracy of the answers by ChatGPT may decrease when it is asked about topics with limited published information, such as new drugs and diseases.

Renin-angiotensin-aldosterone system inhibitors as a risk factor for chronic subdural hematoma recurrence: A matter of debate.

OBJECTIVES: Chronic subdural hematoma (cSDH) is a common central nervous system condition. Recent reports indicate that cSDH affects long-term prognosis; however, its definitive risk factors remain unknown. An antihypertensive drug, renin-angiotensin-aldosterone system inhibitors (RAASi), can affect vascular permeability and cell proliferation processes, which may suppress the recurrence of cSDH. However, several studies have reported negative results to this effect. Therefore, we aimed to evaluate antihypertensive drugs, including RAASi, as risk factors for recurrent cSDH. MATERIALS AND METHODS: A total of 203 consecutive cases of surgically treated cSDH were retrospectively reviewed. Clinical and radiological parameters were compared between the groups with and without cSDH recurrence to identify risk factors. RESULTS: Of the included cases, 68 (33.5%) used RAASi and 37 (18.2%) developed recurrence within 60 days of surgery. In the multiple logistic regression analysis adjusted by composite risk score, the odds ratios (95% confidence interval) of RAASi, calcium channel blockers, diuretics, ß and α blockers, for the recurrent risk of cSDH after surgery were 2.49 (1.16, 5.42), 1.79 (0.84, 3.82), 1.83 (0.62, 4.87), 0.90 (0.28, 2.44), and 0.96 (0.21, 3.20), respectively. The Cox proportional hazard model also demonstrated that RAASi-use was an independent risk factor for cSDH recurrence. CONCLUSIONS: Present series suggests RAASi-use as a risk factor for cSDH recurrence, although the role of RAASi-use in cSDH remains debatable. Further studies for deeper understanding of the microenvironment of hematoma and the surroundings are preferable. (235 words).

High plasma aldosterone concentration is associated with worse 24-h ambulatory blood pressure profile in patients with primary aldosteronism.

Patients with primary aldosteronism (PA) have a higher risk of cardiovascular disease (CVD) than essential hypertension due to underlying hyperaldosteronism. However, the association between high plasma aldosterone concentrations (PACs) and diurnal blood pressure (BP) variation has not been fully elucidated. Because abnormal ambulatory blood pressure monitoring (ABPM) profiles are associated with increased CVD risk, we investigated the association between PACs and the ABPM profile in 36 patients with PA diagnosed by confirmatory tests who underwent adrenal venous sampling (AVS). The clinical parameters were measured during hospitalization for AVS. The dietary salt intake of hospitalized patients was controlled at 6 g/day. During AVS, blood samples were collected from the inferior vena cava before and 1 h after adrenocorticotropic hormone (ACTH) stimulation to measure the PACs. The post-stimulation PAC had a significant negative correlation with nocturnal BP dipping rates (R = -0.387, p = 0.020), whereas pre-stimulation PAC did not (R = -0.217, p = 0.204). The nocturnal BP dipping rates were significantly lower in the high PAC group (PAC higher than the median) than low PAC group (PAC lower than the median) (p = 0.009). Multiple regression analysis revealed that high PAC was an independent factor contributing to low nocturnal BP dipping rates (ß = -0.316, p = 0.038). In conclusion, in patients with PA, hyperaldosteronism is associated with nocturnal hypertension, which is an important risk factor for CVD. Additionally, ACTH stimulation may improve the sensitivity of PACs as a clinical indicator of nocturnal hypertension.

Blunted humoral immune response to the fourth dose of BNT162b2 COVID-19 vaccine in patients undergoing hemodialysis.

BACKGROUND: We aimed to investigate the impact of a fourth dose of BNT162b2 vaccine (Comirnaty®, Pfizer-BioNTech) on anti-SARS-CoV-2 (anti-S IgG) antibody titers in patients receiving hemodialysis (HD) and healthcare workers (HCWs). METHODS: A multi-institutional retrospective study at five dialysis clinics in Japan was conducted using 238 HD patients and 58 HCW controls who received four doses of the BNT162b2 mRNA vaccine. Anti-S IgG titers were measured at 1, 3, and 6 months after the second dose, at 1 and 5/6 months after the third dose, and at 1 month after the fourth dose of vaccine. RESULTS: The log anti-S IgG titers of the HD patients after the second vaccination were significantly lower than those of the control group, but equalized 1 month after the third vaccination: 9.94 (95% CI 9.82-10.10) vs. 9.81 (95% CI 9.66-9.96), (P = 0.32). In both groups, the fold-increase in anti-S IgG titers was significantly lower after the fourth dose than after the third dose of vaccine. In addition, there was a strong negative correlation between antibody titers 1 month after the fourth vaccination and antibody titers immediately before the vaccination. In both groups, the waning rate of anti-S IgG titers from the post-vaccination peak level after the third vaccine dose was significantly slower than that after the second dose. CONCLUSIONS: These findings suggest that the humoral immune response was blunted after the fourth dose of the conventional BNT162b2 vaccine. However, multiple vaccinations could extend the window of humoral immune protection.

Effect of the interaction between the visceral-to-subcutaneous fat ratio and aldosterone on cardiac function in patients with primary aldosteronism.

Primary aldosteronism is the most frequent secondary hypertensive disease and is characterized by an elevated risk for cardiovascular disease. The current standard treatments are adrenalectomy and/or administration of mineralocorticoid receptor blockers, both of which are effective at ameliorating hypertension via intervention for hyperaldosteronism. However, both of these approaches have side effects and contraindications, and mineralocorticoid receptor blockers also have limited preventive efficacy against cardiovascular events. Recently, in vitro experiments have shown that aldosterone regulation is closely related to abdominal fat accumulation and that there is crosstalk between aldosterone and visceral fat tissue accumulation. We previously reported that this interaction was clinically significant in renal dysfunction; however, its effects on the heart remain unclear. Here, we analyzed data from 49 patients with primary aldosteronism and 29 patients with essential hypertension to examine the potential effect of the interaction between the ratio of visceral-to-subcutaneous fat tissue volume and the plasma aldosterone concentration on echocardiographic indices, including the tissue Doppler-derived E/e' ratio. A significant interaction was found in patients with primary aldosteronism (p < 0.05), indicating that patients with the combination of a high plasma aldosterone concentration and high visceral-to-subcutaneous fat ratio show an increased E/e' ratio, which is a well-known risk factor for future cardiovascular events. Our results confirm the clinical importance of the interaction between aldosterone and abdominal fat tissue, suggesting that an improvement in the visceral-to-subcutaneous fat ratio may be synergistically and complementarily effective in reducing the elevated risk of cardiovascular disease in patients with primary aldosteronism when combined with conventional therapies for reducing aldosterone activity. A significant effect of the interaction between plasma aldosterone concentration and the visceral-to-subcutaneous fat ratio on the tissue Doppler-derived E/e' ratio in patients with primary aldosteronism.

The implication of calf circumference and grip strength in osteoporosis and bone mineral density among hemodialysis patients.

BACKGROUND: Chronic kidney disease-mineral and bone disorder (CKD-MBD), nutritional status, and uremia management have been emphasized for bone management in hemodialysis patients. Nevertheless, valuable data on the importance of muscle mass in bone management are limited, including whether conventional management alone can prevent osteoporosis. Thus, the importance of muscle mass and strength, independent of the conventional management in osteoporosis prevention among hemodialysis patients, was evaluated. METHODS: Patients with a history of hemodialysis 6 months or longer were selected. We assessed the risk for osteoporosis associated with calf circumference or grip strength using multivariable adjustment for indices of CKD-MBD, nutrition, and dialysis adequacy. Moreover, the associations between bone mineral density (BMD), calf circumference, grip strength, and bone metabolic markers were also evaluated. RESULTS: A total of 136 patients were included. The odds ratios (95% confidence interval) for osteoporosis at the femoral neck were 1.25 (1.04-1.54, P < 0.05) and 1.08 (1.00-1.18, P < 0.05) per 1 cm shorter calf circumference or 1 kg weaker grip strength, respectively. Shorter calf circumference was significantly associated with a lower BMD at the femoral neck and lumbar spine (P < 0.001). Weaker grip strength was also associated with lower BMD at the femoral neck (P < 0.01). Calf circumference or grip strength was negatively correlated with bone metabolic marker values. CONCLUSION: Shorter calf circumference or weaker grip strength was associated with osteoporosis risk and lower BMD among hemodialysis patients, independent of the conventional therapies.

Omega-3 Fatty Acids Reduce Remnant-like Lipoprotein Cholesterol and Improve the Ankle-Brachial Index of Hemodialysis Patients with Dyslipidemia: A Pilot Study.

Background and Objectives: Omega-3 fatty acids have potent lipid-lowering and antiplatelet effects; however, randomized controlled trials have yet to examine the effect of high-dose omega-3 fatty acid administration on peripheral artery disease (PAD) in hemodialysis patients with dyslipidemia. Therefore, this study aimed to evaluate the effects of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on the ankle-brachial index (ABI) and remnant-like lipoprotein cholesterol (RLP-C) levels, which are indicators of PAD severity. Materials and Methods: Thirty-eight participants (mean age: 73.6 ± 12.7 years) were randomly assigned using stratified block randomization to either conventional therapy alone or conventional therapy supplemented with high-dose EPA/DHA (EPA: 1860 mg; DHA: 1500 mg) for a three-month intervention period. Patients in the conventional therapy alone group who opted to continue were provided with a low-dose EPA/DHA regimen (EPA: 930 mg; DHA: 750 mg) for an additional three months. The baseline and 3-month values for RLP-C, an atherogenic lipid parameter, and the ABI were recorded. Results: The results of the 3-month assessments revealed that the mean RLP-C changes were -3.25 ± 3.15 mg/dL and 0.44 ± 2.53 mg/dL in the EPA/DHA and control groups, respectively (p < 0.001), whereas the changes in the mean ABI values were 0.07 ± 0.11 and -0.02 ± 0.09 in the EPA/DHA and control groups, respectively (p = 0.007). In the EPA/DHA group, a significant negative correlation was found between the changes in RLP-C levels and the ABI (r = -0.475, p = 0.04). Additionally, the change in the RLP-C levels independently influenced the change in the ABI in the EPA/DHA group, even after adjusting for age, sex, and statin use (p = 0.042). Conclusions: Add-on EPA/DHA treatment improved the effectiveness of conventional therapy (such as statin treatment) for improving the ABI in hemodialysis patients with dyslipidemia by lowering RLP-C levels. Therefore, clinicians involved in dialysis should focus on RLP-C when considering residual cardiovascular disease risk in hemodialysis patients and should consider screening patients with elevated levels.

SARS-CoV-2 spike protein antibody titers 6 months after SARS-CoV-2 mRNA vaccination among patients undergoing hemodialysis in Japan.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination is shown to prevent severe illness and death in hemodialysis (HD) patients, but the immune response to vaccines is reduced in this population. This study compared SARS-CoV-2 spike protein antibody titers between HD patients and healthy controls in Japan for up to 6 months following vaccination. METHODS: A multi-institutional retrospective study at five clinics in Japan was conducted using 412 HD patients and 156 healthy controls who received two doses of the BNT162b2 (Pfizer-BioNTech) mRNA vaccine. Anti-SARS-CoV-2 spike protein S1 IgG antibody titers were measured at 1, 3, and 6 months after the second dose. The attenuation speed was calculated as slope (i.e., -ß) using a linear mixed-effects model toward the log-transformed antibody titers. RESULTS: The HD group had significantly lower month 1 antibody titers (Ab-titer-1) than the controls, and these remained lower through month 6 (95% CI: 2617.1 (1296.7, 5240.8) vs. 7285.4 (4403.9, 11,000.0) AU/mL at Ab-titer-1, and 353.4 (178.4, 656.3) vs. 812.0 (498.3, 1342.7) AU/mL at Ab-titer-6 (p < 0.001, respectively)). Lower log Ab-titer-1 levels in the HD group were significantly associated with a lower log Ab-titer-6 (0.90 [0.83, 0.97], p < 0.001). The -ß values in the HD patients and healthy controls were -4.7 ± 1.1 and -4.7 ± 1.4 (year-1), respectively. CONCLUSION: SARS-CoV-2 spike protein antibody titers were significantly lower in HD patients than in healthy controls at 1 (peak) and 6 months after the second vaccination. Low peak antibody titers contributed to low 6-month antibody titers.

Efficacy of tolvaptan on advanced chronic kidney disease with heart failure: a randomized controlled trial.

BACKGROUND: Tolvaptan (TLV) is reported to improve diuretic effects in patients with chronic kidney disease (CKD) when furosemide (FUR) is not sufficiently effective. However, it is not clear whether TLV addition is effective for advanced CKD patients with heart failure. METHODS: An open-label, parallel-group randomized trial was performed. The subjects were 33 patients with CKD stage G3-G5 who had fluid overload despite taking 20-100 mg/day FUR. They were divided into two groups: a group administered 15 mg/day TLV plus their original FUR dose for 7 days (TLV group), and a group administered 120-200 mg/day FUR (i.e., 100 mg/day over their previous dose) for 7 days (FUR group). RESULTS: The mean change in urine volume was significantly higher in the TLV group compared to the FUR group (637 ml vs 119 ml; p < 0.05). The difference was greater when the urine osmolality before treatment was high. Serum creatinine was increased only in the FUR group. The incidence of worsening renal function (WRF) was significantly lower in the TLV group (18.8% vs 58.8%; p < 0.05). Serum sodium decreased significantly in the FUR group, but did not change in the TLV group. CONCLUSIONS: In patients with advanced CKD with fluid overload, the addition of TLV achieved a significantly higher urine volume with less adverse effects on renal function compared with increasing the dose of FUR. The efficacy and safety of TLV were higher in patients who had higher urine osmolality and lower serum sodium before treatment. CLINICAL TRIAL REGISTRATION: UMIN000014763.

Japan Endocrine Society clinical practice guideline for the diagnosis and management of primary aldosteronism 2021.

Primary aldosteronism (PA) is associated with higher cardiovascular morbidity and mortality rates than essential hypertension. The Japan Endocrine Society (JES) has developed an updated guideline for PA, based on the evidence, especially from Japan. We should preferentially screen hypertensive patients with a high prevalence of PA with aldosterone to renin ratio ≥200 and plasma aldosterone concentrations (PAC) ≥60 pg/mL as a cut-off of positive results. While we should confirm excess aldosterone secretion by one positive confirmatory test, we could bypass patients with typical PA findings. Since PAC became lower due to a change in assay methods from radioimmunoassay to chemiluminescent enzyme immunoassay, borderline ranges were set for screening and confirmatory tests and provisionally designated as positive. We recommend individualized medicine for those in the borderline range for the next step. We recommend evaluating cortisol co-secretion in patients with adrenal macroadenomas. Although we recommend adrenal venous sampling for lateralization before adrenalectomy, we should carefully select patients rather than all patients, and we suggest bypassing in young patients with typical PA findings. A selectivity index ≥5 and a lateralization index >4 after adrenocorticotropic hormone stimulation defines successful catheterization and unilateral subtype diagnosis. We recommend adrenalectomy for unilateral PA and mineralocorticoid receptor antagonists for bilateral PA. Systematic as well as individualized clinical practice is always warranted. This JES guideline 2021 provides updated rational evidence and recommendations for the clinical practice of PA, leading to improved quality of the clinical practice of hypertension.