Adrenergic Innervation of the Mesenteric Arteries in Wistar-Kyoto Rats, Spontaneously Hypertensive Rats and Rats Treated with Monosodium Glutamate.

The adrenergic innervation of the mesenteric arteries in Wistar- Kyoto rats, spontaneously hypertensive rats (SHR) and rats neonatally treated with monosodium glutamate (MSG rats) was examined by using glyoxylic acid fluorescence histochemistry with quantitative analysis, by assaying tissue catecholamines with high performance liquid chromatography, and partly by electron microscopy. In the mesenteric arteries of SHR, fluorescence histochemistry study revealed that the plexus density of fluorescent nerve fibers was significantly higher, and tissue norepinephrine was increased as compared to control WKY. On the contrary, in the mesenteric arteries of MSG rats, the plexus density was reduced, through no significant difference was observed in catecholamine contents. Electron microscopic examination revealed that many axon bundles were adjacent to the external elastic lamina, and that occasionally the basement membranes of axon and smooth muscle cell were fused together for an at least 130 nm neuromuscular distance. The present study suggests that the adrenergic nerves of the mesenteric artery of SHR have an increase in activity and that those of MSG rats may be accompanied by a reduction in the sympathetic nerve activity

Gastric Acid Secretion of Rats with Alterative Autonomic Nervous System

The role of the autonomic nervous system in the generation mechanism of gastric stress ulcers has long been attracting attention. We have been investigating the ulcer formation in the spontaneously hypertensive rat (SHR) thought to have a functionally facilitated sympathetic nervous system and in the MGS rat in which the function of the sympathetic nervous system may be attenuated. In the present study, we studied the state of gastric acid secretion under a pyloric ligation condition in these rat species, using WKY rats as the control. The pylorus was ligated for 4 hrs, and the volume and pH of gastric juice and the volume of gastric acid secreted were measured. Both SHRs and MSG rats showed higher pH values and smaller volume of secreted acid than WKY rats. Ulcer formation in SHRs was milder than in control rats as reported previously, and this was thought to be related to the high pH value and the low gastric acid secretion observed in the present study. Although ulcer formation in MSG rats was more frequent than in control animals, factors such as mucosal blood flow etc. were suggested to be rather responsible because of the high pH value and low acid secretion in this species

A Genetic Variant in the IL-17 Promoter Is Functionally Associated with Acute Graft-Versus-Host Disease after Unrelated Bone Marrow Transplantation

Interleukin IL-17 is a proinflammatory cytokine that has been implicated in the pathogenesis of various autoimmune diseases. The single nucleotide polymorphism (SNP), rs2275913, in the promoter region of the IL-17 gene is associated with susceptibility to ulcerative colitis. When we examined the impact of rs2275913 in a cohort consisting of 438 pairs of patients and their unrelated donors transplanted through the Japan Marrow Donor Program, the donor IL-17 197A allele was found to be associated with a higher risk of acute graft-versus-host disease (GVHD; hazard ratio [HR], 1.46; 95% confidence interval [CI], 1.00 to 2.13; P = 0.05). Next, we investigated the functional relevance of the rs2275913 SNP. In vitro stimulated T cells from healthy individuals possessing the 197A allele produced significantly more IL-17 than those without the 197A allele. In a gene reporter assay, the 197A allele construct induced higher luciferase activity than the 197G allele, and the difference was higher in the presence of T cell receptor activation and was abrogated by cyclosporine treatment. Moreover, the 197A allele displayed a higher affinity for the nuclear factor activated T cells (NFAT), a critical transcription factor involved in IL-17 regulation. These findings substantiate the functional relevance of the rs2275913 polymorphism and indicate that the higher IL-17 secretion by individuals with the 197A allele likely accounts for their increased risk for acute GVHD and certain autoimmune diseases

AN AUTOPSY CASE OF PARATHYROID CARCINOMA

A case of hyperfunctioning parathyroid carcinoma was found in a 78-year-old female who had suffered from hypercalcemia for 5 years. She died of renal failure and pulmonary edema. Autopsy revealed an encapsulated tumor arising from the left upper parathyroid gland. Histologically, fibrous trabeculae, capsular invasion and blood vessel invasion were occasionally present in this tumor, suggesting that this tumor was malignant. However, mitotic figures were rarely observed. We reviewed reported cases of parathyroid carcinoma and discussed about the significance of mitosis for diagnosis

Morphometrical Study on the Sclerotic Inferior Vena Cava in Chronic Lung Disease

The purpose of this study is to determine the relationship between chronic lung disease (CLD) and morphological changes in the inferior vena cava (IVC) from postmortem materials. The IVC and pulmonary truncus were obtained from 70 cases with CLD and/or cor pulmonale and from 23 controls. The tissues were processed for light and electron microscopic studies. The adventitia was by far the thickest component of the IVC wall. The total wall, intimal, and adventitial thicknesses were all significantly greater in the CLD cases than in the controls (p<0.001), but there was no significant difference in the ratio of adventitia thickness to wall thickness. The incidence of intimal thickening was 13.0% and 37.3% in controls and in CLD respectively. Electron microscopic examination of the IVC from the CLD cases revealeda marked increase in the amount of extracellular matrix including collagen, elastic fibers and ground substances in the adventitia as compared with the controls. No foam cells were detected in the thickened intima of the IVC. PA, right ventricular thickness and RV/LV ratio were greater in CLD than in controls. The blood gas levels of the CLD cases indicated obvious hypoxia (PaO2 54.2 mmHg). This study suggests that increased venous pressure and hypoxia might be implicated in the pathogenesis of phlebosclerosis in patients with CLD

Lower In-Hospital Mortality With Beta-Blocker Use at Admission in Patients With Acute Decompensated Heart Failure

[Background] It remains unclear whether beta‐blocker use at hospital admission is associated with better in‐hospital outcomes in patients with acute decompensated heart failure. [Methods and Results] We evaluated the factors independently associated with beta‐blocker use at admission, and the effect of beta‐blocker use at admission on in‐hospital mortality in 3817 patients with acute decompensated heart failure enrolled in the Kyoto Congestive Heart Failure registry. There were 1512 patients (39.7%) receiving, and 2305 patients (60.3%) not receiving beta‐blockers at admission for the index acute decompensated heart failure hospitalization. Factors independently associated with beta‐blocker use at admission were previous heart failure hospitalization, history of myocardial infarction, atrial fibrillation, cardiomyopathy, and estimated glomerular filtration rate <30 mL/min per 1.73 m2. Factors independently associated with no beta‐blocker use were asthma, chronic obstructive pulmonary disease, lower body mass index, dementia, older age, and left ventricular ejection fraction <40%. Patients on beta‐blockers had significantly lower in‐hospital mortality rates (4.4% versus 7.6%, P<0.001). Even after adjusting for confounders, beta‐blocker use at admission remained significantly associated with lower in‐hospital mortality risk (odds ratio, 0.41; 95% CI, 0.27–0.60, P<0.001). Furthermore, beta‐blocker use at admission was significantly associated with both lower cardiovascular mortality risk and lower noncardiovascular mortality risk. The association of beta‐blocker use with lower in‐hospital mortality risk was relatively more prominent in patients receiving high dose beta‐blockers. The magnitude of the effect of beta‐blocker use was greater in patients with previous heart failure hospitalization than in patients without (P for interaction 0.04). [Conclusions] Beta‐blocker use at admission was associated with lower in‐hospital mortality in patients with acute decompensated heart failure

Sex differences in patients with acute decompensated heart failure in Japan: observation from the KCHF registry

Aims: The association between sex and long‐term outcome in patients hospitalized for acute decompensated heart failure (ADHF) has not been fully studied yet in Japanese population. The aim of this study was to determine differences in baseline characteristics and management of patients with ADHF between women and men and to compare 1‐year outcomes between the sexes in a large‐scale database representing the current real‐world clinical practice in Japan. Methods and results: Kyoto Congestive Heart Failure registry is a prospective cohort study enrolling consecutive patients hospitalized for ADHF in Japan among 19 centres. Baseline characteristics, clinical presentation, management, and 1‐year outcomes were compared between men and women. A total of 3728 patients who were alive at discharge constituted the current study population. There were 1671 women (44.8%) and 2057 men. Women were older than men [median (IQR): 83 (76–88) years vs. 77 (68–84) years, P < 0.0001]. Hypertensive and valvular heart diseases were more prevalent in women than in men (28.0% vs. 22.5%, P = 0.0001; and 26.9% vs. 14.0%, P < 0.0001, respectively), whereas ischaemic aetiology was less prevalent in women than in men (20.0% vs. 32.5%, P < 0.0001). Women less often had reduced left ventricular ejection fraction (<40%) than men (27.5% vs. 45.1%, P < 0.0001). The cumulative incidence of all‐cause death or hospitalization for heart failure was not significantly different between women and men (33.6% vs. 34.3%, P = 0.71), although women were substantially older than men. After multivariable adjustment, the risk of all‐cause death or hospitalization for heart failure was significantly lower among women (adjusted hazard ratio: 0.84, 95% confidence interval: 0.74–0.96, P = 0.01). Conclusions: Women with heart failure were older and more often presented with preserved EF with a non‐ischaemic aetiology and were associated with a reduced adjusted risk of 1‐year mortality compared with men in the Japanese population

Appetite loss at discharge from acute decompensated heart failure: Observation from KCHF registry

OBJECTIVE: The complex link between nutritional status, protein and lipid synthesis, and immunity plays an important prognostic role in patients with heart failure. However, the association between appetite loss at discharge and long-term outcome remains unclear. METHODS: The Kyoto Congestive Heart Failure registry is a prospective cohort study that enrolled consecutive patients hospitalized for acute decompensated heart failure (ADHF) in Japan. We assessed 3528 patients alive at discharge, and for whom appetite and follow-up data were available. We compared one-year clinical outcomes in patients with and without appetite loss at discharge. RESULTS: In the multivariable logistic regression analysis using 19 clinical and laboratory factors with P value 1.0mg/dL (OR: 1.49, 95%CI: 1.04-2.14, P = 0.03), and presence of edema at discharge (OR: 4.30, 95%CI: 2.99-6.22, P<0.001) were associated with an increased risk of appetite loss at discharge, whereas ambulatory status (OR: 0.57, 95%CI: 0.39-0.83, P = 0.004) and the use of ACE-I/ARB (OR: 0.70, 95% CI: 0.50-0.98, P = 0.04) were related to a decreased risk in the presence of appetite loss. The cumulative 1-year incidence of all-cause death (primary outcome measure) was significantly higher in patients with appetite loss than in those without appetite loss (31.0% vs. 15.0%, P<0.001). The excess adjusted risk of appetite loss relative to no appetite loss remained significant for all-cause death (hazard ratio (HR): 1.63, 95%CI: 1.29-2.07, P<0.001). CONCLUSIONS: Loss of appetite at discharge was associated with worse 1-year mortality in patients with ADHF. Appetite is a simple, reliable, and useful subjective marker for risk stratification of patients with ADHF

Public assistance in patients with acute heart failure: a report from the KCHF registry

AIMS: There is a scarcity of data on the post-discharge prognosis in acute heart failure (AHF) patients with a low-income but receiving public assistance. The study sought to evaluate the differences in the clinical characteristics and outcomes between AHF patients receiving public assistance and those not receiving public assistance. METHODS AND RESULTS: The Kyoto Congestive Heart Failure registry was a physician-initiated, prospective, observational, multicentre cohort study enrolling 4056 consecutive patients who were hospitalized due to AHF for the first time between October 2014 and March 2016. The present study population consisted of 3728 patients who were discharged alive from the index AHF hospitalization. We divided the patients into two groups, those receiving public assistance and those not receiving public assistance. After assessing the proportional hazard assumption of public assistance as a variable, we constructed multivariable Cox proportional hazard models to estimate the risk of the public assistance group relative to the no public assistance group. There were 218 patients (5.8%) receiving public assistance and 3510 (94%) not receiving public assistance. Patients in the public assistance group were younger, more frequently had chronic coronary artery disease, previous heart failure hospitalizations, current smoking, poor medical adherence, living alone, no occupation, and a lower left ventricular ejection fraction than those in the no public assistance group. During a median follow-up of 470 days, the cumulative 1 year incidences of all-cause death and heart failure hospitalizations after discharge did not differ between the public assistance group and no public assistance group (13.3% vs. 17.4%, P = 0.10, and 28.3% vs. 23.8%, P = 0.25, respectively). After adjusting for the confounders, the risk of the public assistance group relative to the no public assistance group remained insignificant for all-cause death [hazard ratio (HR), 0.97; 95% confidence interval (CI), 0.69-1.32; P = 0.84]. Even after taking into account the competing risk of all-cause death, the adjusted risk within 180 days in the public assistance group relative to the no public assistance group remained insignificant for heart failure hospitalizations (HR, 0.93; 95% CI, 0.64-1.34; P = 0.69), while the adjusted risk beyond 180 days was significant (HR, 1.56; 95% CI, 1.07-2.29; P = 0.02). CONCLUSIONS: The AHF patients receiving public assistance as compared with those not receiving public assistance had no significant excess risk for all-cause death at 1 year after discharge or a heart failure hospitalization within 180 days after discharge, while they did have a significant excess risk for heart failure hospitalizations beyond 180 days after discharge. CLINICAL TRIAL REGISTRATION: https://clinicaltrials.gov/ct2/show/NCT02334891 (NCT02334891) and https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000017241 (UMIN000015238)

Tricuspid regurgitation in elderly patients with acute heart failure: insights from the KCHF registry

AIMS: Several studies demonstrated that tricuspid regurgitation (TR) is associated with poor clinical outcomes. However, data on patients with TR who experienced acute heart failure (AHF) remains scarce. The purpose of this study is to evaluate the association between TR and clinical outcomes in patients admitted with AHF, using a large-scale Japanese AHF registry. METHODS AND RESULTS: The current study population consisted of 3735 hospitalized patients due to AHF in the Kyoto Congestive Heart Failure (KCHF) registry. TR grades were assessed according to the routine clinical practice at each participating centre. We compared the baseline characteristics and outcomes according to the severity of TR. The primary outcome was all-cause death. The secondary outcome was hospitalization for heart failure (HF). The median age of the entire study population was 80 (interquartile range: 72-86) years. One thousand two hundred five patients (32.3%) had no TR, while mild, moderate, and severe TR was found in 1537 patients (41.2%), 776 patients (20.8%), and 217 patients (5.8%), respectively. Pulmonary hypertension, significant mitral regurgitation, and atrial fibrillation/flutter were strongly associated with the development of moderate/severe of TR, while left ventricular ejection fraction <50% was inversely associated with it. Among 993 patients with moderate/severe TR, the number of patients who underwent surgical intervention for TR within 1 year was only 13 (1.3%). The median follow-up duration was 475 (interquartile range: 365-653) days with 94.0% follow-up at 1 year. As the TR severity increased, the cumulative 1 year incidence of all-cause death and HF admission proportionally increased ([14.8%, 20.3%, 23.4%, 27.0%] and [18.9%, 23.0%, 28.5%, 28.4%] in no, mild, moderate, and severe TR, respectively). Compared with no TR, the adjusted risks of patients with mild, moderate, and severe TR were significant for all-cause death (hazard ratio [95% confidence interval]: 1.20 [1.00-1.43], P = 0.0498, 1.32 [1.07-1.62], P = 0.009, and 1.35 [1.00-1.83], P = 0.049, respectively), while those were not significant for hospitalization for HF (hazard ratio [95% confidence interval]: 1.16 [0.97-1.38], P = 0.10, 1.19 [0.96-1.46], P = 0.11, and 1.20 [0.87-1.65], P = 0.27, respectively). The higher adjusted HRs of all the TR grades relative to no TR were significant for all-cause death in patients aged <80 years, but not in patients aged ≥80 years with significant interaction. CONCLUSIONS: In a large Japanese AHF population, the grades of TR could successfully stratify the risk of all-cause death. However, the association of TR with mortality was only modest and attenuated in patients aged 80 or more. Further research is warranted to evaluate how to follow up and manage TR in this elderly population