Esaxerenone: blood pressure reduction and cardiorenal protection without reflex sympathetic activation in salt-loaded stroke-prone spontaneously hypertensive rats.

Mineralocorticoid receptor (MR) is involved in the mechanisms of blood pressure elevation, organ fibrosis, and inflammation. MR antagonists have been used in patients with hypertension, heart failure, or chronic kidney disease. Esaxerenone, a recently approved MR blocker with a nonsteroidal structure, has demonstrated a strong blood pressure-lowering effect. However, blood pressure reduction may lead to sympathetic activation through the baroreflex. The effect of esaxerenone on the sympathetic nervous system remains unclear. We investigated the effect of esaxerenone on organ damage and the sympathetic nervous system in salt-loaded stroke-prone spontaneously hypertensive rats (SHRSP), a well-established model of essential hypertension with sympathoexcitation and organ damage. Three-week administration of esaxerenone or hydralazine successfully attenuated the blood pressure elevation. Both esaxerenone and hydralazine comparably suppressed left ventricular hypertrophy and urinary albumin excretion. However, renal fibrosis and glomerular sclerosis were suppressed by esaxerenone but not hydralazine. Furthermore, plasma norepinephrine level, a parameter of systemic sympathetic activity, was significantly increased by hydralazine but not by esaxerenone. Consistent with these findings, the activity of the control centers of sympathetic nervous system, the parvocellular region of the paraventricular nucleus in the hypothalamus and the rostral ventrolateral medulla, was enhanced by hydralazine but remained unaffected by esaxerenone. These results suggest that esaxerenone effectively lowers blood pressure without inducing reflex sympathetic nervous system activation. Moreover, the organ-protective effects of esaxerenone appear to be partially independent of its blood pressure-lowering effect. In conclusion, esaxerenone demonstrates a blood pressure-lowering effect without concurrent sympathetic activation and exerts organ-protective effects in salt-loaded SHRSP. Esaxerenone has antihypertensive and cardiorenal protective effects without reflex sympathetic activation in salt-loaded stroke-prone spontaneously hypertensive rats.

Medical care costs according to the stage and subtype of breast cancer in a municipal setting: a case study of Hachioji City, Japan.

BACKGROUND: It is important to assess whether the early detection of breast cancer affects medical care costs. However, research remains scant on the actual medical care costs associated with breast cancer treatment in Japan. This study aimed to determine the medical care costs of breast cancer treatment based on its stage using national health insurance claims data. METHODS: This was an observational study including patients with breast cancer who had undergone breast cancer treatment, as defined by the disease name and related treatment codes. Between August 2013 and June 2016, patients who underwent surgical treatment without axillary lymph node dissection and other radical treatment were classified as the curable group, while those who underwent palliative treatment were classified as the non-curable group. Patients were further stratified by subtype. The total and treatment-specific medical care costs for the five years were calculated using the national health insurance claims data of Hachioji City between August 2013 and May 2021. RESULTS: The mean total medical care costs for the curable and non-curable groups for the 5 years were JPY 3958 thousand (standard deviation 2664) and JPY 8289 thousand (8482), respectively. The mean medical care costs for specific breast cancer treatment for the curable and non-curable groups were JPY 1142 (728) thousand and JPY 3651 thousand (5337), respectively. Further, human epidermal growth factor receptor 2 + , Hormone + patients had the highest mean cost over the 5 years. CONCLUSIONS: The results suggest that the early detection of breast cancer may reduce medical care costs at the patient level.

Contribution of afferent renal nerve signals to acute and chronic blood pressure regulation in stroke-prone spontaneously hypertensive rats.

The activation of sympathetic nervous system plays a critical role in the development of hypertension. The input from afferent renal nerves may affect central sympathetic outflow; however, its contribution to the development of hypertension remains unclear. We investigated the role of afferent renal nerves in acute and chronic blood pressure regulation using normotensive Wistar-Kyoto rats (WKY) and stroke-prone spontaneously hypertensive rats (SHRSP). Acute chemical stimulation of afferent renal nerves elicited larger increases in blood pressure and renal sympathetic nerve activity in young 9-week-old SHRSP compared to WKY. Selective afferent renal denervation (ARDN) and conventional total renal denervation (TRDN) ablating both afferent and efferent nerves in young SHRSP revealed that only TRDN, but not ARDN, chronically attenuated blood pressure elevation. ARDN did not affect plasma renin activity or plasma angiotensin II levels, whereas TRDN decreased both. Neither TRDN nor ARDN affected central sympathetic outflow and systemic sympathetic activity determined by neuronal activity in the parvocellular region of hypothalamic paraventricular nucleus and rostral ventrolateral medulla and by plasma and urinary norepinephrine levels, respectively. Renal injury was not apparent in young SHRSP compared with WKY, suggesting that renal afferent input might not be activated in young SHRSP. In conclusion, the chronic input from afferent renal nerves does not contribute to the development of hypertension in SHRSP despite the increased blood pressure response to the acute stimulation of afferent renal nerves. Efferent renal nerves may be involved in the development of hypertension via activation of the renin-angiotensin system in SHRSP.

Transient receptor potential vanilloid 1-expressing cardiac afferent nerves may contribute to cardiac hypertrophy in accompany with an increased expression of brain-derived neurotrophic factor within nucleus tractus solitarius in a pressure overload model.

INTRODUCTION: Increased sympathetic output contributes to cardiac hypertrophy. Sympathoexcitation is induced by activating the cardiac sympathetic afferent nerves through transient receptor potential vanilloid 1 (TRPV1) in cardiac afferent endings. Brainstem nucleus tractus solitarius (NTS) receives the sensory cardiac afferent inputs. Brain-derived neurotrophic factor (BDNF) is released within NTS from sensory neurons in an activity-dependent manner. Additionally, BDNF in NTS tonically regulates sympathetic activity. Therefore, we hypothesized that TRPV1-expressing cardiac afferent nerves contribute to cardiac hypertrophy in accompany with an increased BDNF expression in NTS. METHODS AND RESULTS: Abdominal aortic banding (AB) or sham operation was conducted in wild-type C57BL/6 J (WT-AB) and TRPV1 knockout mice (TRPV1 KO-AB). At 8 weeks post-operation, echocardiographic left ventricular wall thickness and heart weight/body weight ratio were significantly greater in WT-AB than WT-Sham mice, and these hypertrophic indexes were attenuated in TRPV1 KO-AB mice. Among the groups, left ventricular fractional shortening was not different. The protein levels of TRPV1 in heart and BDNF in NTS were significantly increased in WT-AB compared to WT-Sham mice, whereas BDNF expression in NTS was not increased by AB in TRPV1-KO mice. Chemical ablation of TRPV1-expressing cardiac afferents attenuated the AB-induced cardiac hypertrophy and increase in BDNF in NTS. Sympathetic activity analyzed using heart rate variability, and sympathoexcitatory responses to the stimulation of cardiac afferents were increased in WT-AB compared to WT-Sham mice. CONCLUSION: TRPV1-expressing cardiac afferent nerves may contribute to pressure overload-induced cardiac hypertrophy in accompany with the increased BDNF within NTS.

Medical costs according to the stages of colorectal cancer: an analysis of health insurance claims in Hachioji, Japan.

BACKGROUND: Although the effect of the early detection of colorectal cancer (CRC) on medical costs needs to be clarified, there are few reports on the actual medical costs of CRC patients in Japan. We aimed to identify medical costs according to CRC stage, using health insurance claims. METHODS: This observational study included CRC patients who had received specific treatment for CRC, which was defined by the procedure code and the claim computer processing system code associated with the treatment of CRC. CRC patients who underwent endoscopic or radical surgical treatment were defined as the curable group and those with palliative treatment, including palliative chemotherapy, as the non-curable group. Total medical costs and medical costs of specific treatments for CRC for 3 years were measured using the claims held by Hachioji City from May 2014 to July 2019. RESULTS: This study included 442 patients in the curable group, including 267 patients who underwent endoscopic treatment, and 175 patients who underwent radical surgical treatment, and 161 patients in the non-curable group. The mean (standard deviation) total medical costs in the curable and non-curable groups were 2,130 (2,494) and 8,279 (5,600) thousand Japanese Yen (JPY), respectively. The mean (standard deviation) medical costs for the specific treatment of CRC in the curable and non-curable groups were 408 (352) and 3,685 (3,479) thousand JPY, respectively. CONCLUSIONS: We clarified the actual medical costs of CRC in curable and non-curable groups. These results suggest the effect of early detection of CRC in reducing medical costs.

Increasing hepatitis virus screening uptake at worksites in Japan using nudge theory and full subsidies.

BACKGROUND: Despite the importance of hepatitis screening for decreasing liver cancer mortality, screening rates remain low in Japan. Previous studies show that full subsidies increase screening uptake, but full subsidies are costly and difficult to implement in low-resource settings. Alternatively, applying nudge theory to the message design could increase screening at lower costs. This study examined the effects of both methods in increasing hepatitis virus screening rates at worksites. METHODS: 1496 employees from a Japanese transportation company received client reminders for an optional hepatitis virus screening before their general health checkups. Groups A and B received a client reminder designed based on the principles of "Easy" and "Attractive," while the control group received a client reminder not developed using nudge theory. Additionally, hepatitis virus screening was offered to the control group and group A for a co-payment of JPY 612, but was fully subsidized for group B. The hepatitis virus screening rates among the groups were compared using a Chi-square test with Bonferroni correction, and the risk ratios of group A and group B to the control group were also calculated. To adjust for unobservable heterogeneity per cluster, the regression analysis was performed using generalized linear mixed models. RESULTS: The screening rate was 21.2%, 37.1%, and 86.3% for the control group, group A, and group B, respectively. And the risk ratio for group A was 1.75 (95% confidence interval [CI] 1.45-2.12) and that of group B was 4.08 (95% CI 3.44-4.83). The parameters of group A and group B also were significant when estimated using generalized linear mixed models. However, the cost-effectiveness (incremental cost-effectiveness ratio (ICER)) of the nudge-based reminder with the full subsidies was lower than that of only the nudge-based reminder. CONCLUSIONS: While fully subsidized screening led to the highest hepatitis screening rates, modifying client reminders using nudge theory significantly increased hepatitis screening uptake at lower costs per person.

A Rare Manifestation of Right Ventricular Dysfunction in an Adult Patient With Mucolipidosis Type III α/ß.

Mucolipidosis type III α/ß is an autosomal recessive lysosomal storage disease, caused by the deficient activity of UDP-N-acetyl glucosamine-1-phosphotransferase. The resultant intralysosomal accumulation of partly degraded mucopolysaccharides and sphingolipids causes multiple-organ damage, including the heart. The most documented cardiac manifestation is the thickening and insufficiency of mitral and aortic valves, but there are very few reports about the myocardial involvement. We report a case with mucolipidosis type III α/ß complicated by marked dilatation and dysfunction of the right ventricle, which is quite rare and further broadens the clinical spectrum of the disease.

Marked ST-segment elevation during permanent pacemaker implantation.

Some acute complications are known during permanent pacemaker implantation such as pneumothorax, lead perforation, lead dislodgement, and hemorrhage. ST-segment elevation in electrocardiogram during implantation is rare, but it might indicate critical complication like myocardial ischemia or ventricular perforation. Physicians should pay attention about ST-segment change during pacemaker implantation.