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Background: The predictive ability of neonatal illness severity scores for mortality or morbidity in extremely premature infants has not been extensively studied. We aimed to evaluate the ability of neonatal illness severity scores [Clinical Risk Index for Babies II (CRIB II), Score for Neonatal Acute Physiology II (SNAP-II), and SNAP-Perinatal Extension II (SNAPPE-II)] in predicting mortality and short-term morbidity of extremely premature infants., Methods: This retrospective study involved 171 infants with gestational age (GA) between 22 and 27 weeks who were admitted to the NICU during 2010-2017. Predictive ability of neonatal illness severity scores for mortality and short-term morbidity (bronchopulmonary dysplasia, retinopathy of prematurity, intraventricular hemorrhage, necrotizing enterocolitis, and gastrointestinal perforation) was assessed by comparing their area under the receiver operating characteristic curve., Results: The overall mortality rate was 11.1%. Mortality at 23 weeks' gestation was higher than that at 24-27 weeks' gestation ( p  < .01, adjusted residual 4.5). Neonatal illness severity scores were significantly higher in infants who died than in those who survived ( p  < .01). CRIB II (AUC 0.93, 95% CI 0.85-1.00), SNAP-II (AUC 0.90, 95% CI 0.76-1.00), and SNAPPE-II (AUC 0.95, 95% CI 0.91-0.99) appeared to be excellent predictors and were superior to birth weight (AUC 0.88, 95% CI 0.80-0.95) or GA (AUC 0.84, 95% CI 0.72-0.96) alone in predicting early death (died on <28th postnatal day). CRIB II, SNAP-II, and SNAPPE-II were better predictors of early death than mortality in extremely premature infants. Neonatal illness severity score and short-term morbidity were not strongly associated., Conclusions: The neonatal illness severity scores were excellent predictors of early death in extremely premature infants and might be useful for selecting extremely preterm infants who need intervention.

Background and Aim: Few studies have evaluated risk factors for short-term re-bleeding in patients with colonic diverticular bleeding (CDB). We aimed to reveal risk factors for re-bleeding within a month in patients with CDB., Methods: We retrospectively analyzed clinical course of patients with CDB diagnosed at 10 institutions between 2015 and 2019. Risk factors for re-bleeding within a month were assessed by Cox proportional hazards models., Results: Among 370 patients, 173 (47%) patients had been under the use of antithrombotic agents (ATs) and 34 (9%) experienced re-bleeding within a month. Multivariate analysis revealed that the use of ATs was an independent risk factor for re-bleeding within a month (HR 2.38, 95% CI 1.10-5.50, p =  .028). Furthermore, use of multiple ATs and continuation of ATs were found to be independent risk factors for re-bleeding within a month (HR 3.88, 95% CI 1.49-10.00, p =  .007 and HR 3.30, 95% CI 1.23-8.63, p =  .019, respectively). Two of 370 patients, who discontinued ATs, developed thromboembolic event., Conclusions: Use of ATs was an independent risk factor for short-term re-bleeding within a month in patients with CDB. This was especially the case for the use of multiple ATs and continuation of ATs. However, discontinuation of ATs may increase the thromboembolic events those patients.

Objectives: Both potassium-competitive acid blockers (P-CABs) and proton pump inhibitors (PPIs) are known to be protective against bleeding after gastric endoscopic dissection (ESD) for early gastric cancers. The aim was to compare the effect of PPI and P-CAB treatment against bleeding after gastric ESD., Materials and Methods: This was a single-center, retrospective analysis. Among 541 patients who underwent gastric ESD during the period from 2014 to 2019, we recruited subjects who were treated with PPIs (intravenous lansoprazole followed by oral esomeprazole) or a P-CAB before and after ESD. The incidence of post-ESD bleeding was compared between treatment groups. The risks associated with post-ESD bleeding were examined by univariate and multivariate analyses after propensity score-matching., Results: The overall incidence of post-ESD bleeding was not significantly different between patients treated with PPIs ( n  = 362) and those treated with a P-CAB ( n  = 156) (3.0% vs 2.6%, respectively; p  = .77). Even after propensity score matching ( n  = 153 in each group), the incidence was not significantly different between groups (2.6% vs 2.6%, respectively; p  = 1.00). A multivariate analysis revealed that antithrombotic therapy (OR 4.85, 95% CI 1.14-20.57) was an independent factor associated with post-ESD bleeding., Conclusions: The incidence of post gastric ESD bleeding is not different between patients treated with PPI and patients treated with P-CAB. Antithrombotic therapy is an independent risk factor associated with post-ESD bleeding.

Background: The carotid bulb has a high density of baroreceptors that play an important role in maintaining blood pressure. We hypothesized that atherosclerosis of the carotid bulb would reflect the severity of orthostatic hypotension more accurately than would atherosclerosis of other carotid artery segments., Methods: This cross-sectional study included 198 non-diabetic adults. We measured the cardio-vascular ankle index as an index of arterial stiffness, intima-media thickness in each carotid artery segment (internal carotid artery, carotid bulb, distal and proximal portions, respectively, of the common carotid artery) as a measure of atherosclerosis, and heart rate variability as a measure of cardiac autonomic function. The sit-to-stand test was used to assess severity of orthostatic hypotension., Results: Intima-media thickness of the carotid bulb was correlated with orthostatic systolic blood pressure change (r = -0.218, p = 0.002), cardio-ankle vascular index (r = 0.365, p < 0.001) and heart rate variability parameters. Multivariate regression analysis revealed that among all of the segments, only intima-media thickness of the carotid bulb was an independent predictor of orthostatic systolic blood pressure change (p = 0.022)., Conclusion: Atherosclerosis of the carotid bulb was associated with severity of orthostatic hypotension, arterial stiffening and cardiac autonomic dysfunction than that of other carotid artery segments.

As there may be an association between within-visit blood pressure (BP) variability and cardiovascular disease (CVD), we investigated the clinical significance of this BP variability in non-dialysis chronic kidney disease (CKD) patients., Materials and Methods: According to the median of coefficient of variation (CV) of three systolic BP (SBP) readings within a single visit, we divided hypertensive patients with stage G1-4 CKD already treated with antihypertensive therapy into the high SBP-CV group and the low SBP-CV group. Univariate and multivariate linear regression analyses were also performed to explore the contributing factors to within-visit BP variability., Results: In the high SBP-CV group, the clinic BP, total cholesterol level, dyslipidemia, and past history of CVD were significantly greater, while α 1 -blockers and renin-angiotensin system (RAS) inhibitors usage were significantly reduced compared with the lower SBP-CV group. Within-visit BP variability was significantly and positively correlated with total cholesterol (R = 0.392, P < 0.001) and low-density lipoprotein cholesterol (R = 0.284, P = 0.013). Total cholesterol (β = 0.269, P = 0.024), α 1 -blockers usage (β = -0.260, P = 0.015), and RAS inhibitors usage (β = -0.266, P = 0.017) were shown to independently contribute to the within-visit BP variability after adjustment for age, sex, presence of diabetes, CVD history, statins usage, and clinic SBP., Conclusions: We show that within-visit BP variability may be a clinically relevant factor of CVD risk, and lipid lowering and/or anti-hypertensive therapies using RAS inhibitors and α 1 -blockers may be associated with the improved within-visit BP variability observed in non-dialysis CKD patients.

Diuretics or calcium channel blockers (CCBs) are used concomitantly with an angiotensin II receptor blocker (ARB). However, it is not established which ARB-based combination therapy is the most effective and safe. This prospective randomized open-label study compared the efficacy and safety of a fixed-dose tablet of losartan (LST)-hydrochlorothiazide (HCTZ) (n = 99) and LST-amlodipine (AML) (n = 77) in Japanese patients whose hypertension was uncontrolled by ARB monotherapy. Blood pressure changed similarly over the 12-month study period. Only LST-HCTZ significantly increased serum uric acid (SUA) in patients with low baseline SUA (<5.6 mg/dL) but not in patients with high baseline SUA.

Recent guidelines recommend combination antihypertensive therapy to achieve the target blood pressure (BP) and to suppress target organ damage. This study aimed to examine the beneficial effects of combination therapy with candesartan and amlodipine on BP control and markers of target organ function in Japanese essential hypertensive patients (N = 20) who did not achieve the target BP level during the monotherapy period with either candesartan or amlodipine. After the monotherapy period, for patients already being treated with amlodipine, a once-daily 8 mg dose of candesartan was added on during the combination therapy period (angiotensin II receptor blocker [ARB] add-on group, N = 10), and a once-daily 5 mg dose of amlodipine was added on for those already being treated with candesartan (calcium channel blocker [CCB] add-on group, N = 10). Combination therapy with candesartan and amlodipine for 12 weeks significantly decreased clinic and home systolic blood pressure (SBP) and diastolic blood pressure (DBP). In addition, the combination therapy was able to significantly reduce urine albumin excretion without decrease in estimated glomerular filtration ratio and resulted in significant improvements in brachial-ankle pulse wave velocity, central SBP, and insulin sensitivity. Furthermore, the CCB add-on group showed a significantly greater decrease in clinic and home DBP than the ARB add-on group. The calcium channel blocker add-on group also exhibited better improvements in vascular functional parameters than the ARB add-on group. These results suggest that combination therapy with candesartan and amlodipine is an efficient therapeutic strategy for hypertension with pleiotropic benefits.

Strict blood pressure (BP) control is reportedly important for the management of hypertensive patients with chronic kidney disease (CKD). The purpose of this cross-sectional study was to examine whether the variables of ambulatory BP and the heart rate (HR) profile, central hemodynamics, and arterial stiffness were closely related to the renal function parameters (urine albumin excretion rate [UACR] and estimated glomerular filtration rate [eGFR]) observed in 25 consecutive hospitalized hypertensive patients with CKD. There were significant positive relationships between UACR and 24-hour, daytime, and nighttime ambulatory systolic BP. In addition, there were significant negative relationships between UACR and 24-hour and daytime HR variability. The circulating B-type natriuretic peptide level and hemoglobin A1c were also positively related to UACR. With respect to eGFR, although the 24-hour and nighttime HR variability were positively associated with eGFR, the circulating pentosidine and nighttime HR had a negative relationship with eGFR. On the other hand, central hemodynamics and arterial stiffness did not exhibit any significant association with renal function parameters. These results indicate that ambulatory BP and the HR profile are closely modulated by renal function deterioration. Further studies are needed to investigate the causal relationship between ambulatory BP and the HR profile and renal function parameters in hypertensive patients with CKD.

Blood pressure (BP) variability is calculated as the standard deviation of ambulatory BP. Blood pressure variability is associated with the cardiovascular morbidity; however whether it is related to target organ damage is controversial. In this study we examined a possible relationship between the BP variability and left ventricular hypertrophy (LVH), and between BP variability and brachial-ankle pulse wave velocity (baPWV). The present study was conducted on 111 consecutive Japanese hypertensive patients who were hospitalized for the educational program in our hospital under stable sodium chloride intake (6 g/day). Blood pressure measurements were at 30-minute intervals all day. In a multivariable analysis adjusted with confounding factor, LVH was associated with 24-hour systolic BP (SBP), 24 hour diastolic BP (DBP), daytime SBP, daytime DBP, nighttime SBP, and nighttime DBP. Additionally, nighttime DBP variability was related to LVH. By the same method, baPWV as a dependent variable was related to 24-hour SBP and nighttime SBP. Furthermore, nighttime SBP variability was concerned with baPWV. The LVH was associated with not only BP level but also with nighttime DBP variability. The baPWV was also related not only to BP level but also to nighttime SBP variability.

We examined risk factors for coronary heart disease (CHD) by ambulatory blood pressure (BP) monitoring in 72 diabetic hypertensives who were hospitalized for the educational program. The patients were divided into two groups (CHD group, 19 subjects; and non-CHD group, 53 subjects) along with or without co-existing CHD. On ambulatory BP monitoring, no significant differences were found between the groups regarding BP values through the day. However, the CHD group had a significantly greater BP variability than non-CHD group. The result of logistic regression analysis demonstrated that nighttime systolic BP variability was an independent risk factor for CHD.

The purpose of this study was to examine a possible difference in the 24-h blood pressure (BP) profile between hypertensives with diabetic nephropathy (DN) and those with non-diabetic glomerulopathy (non-DN). We measured 24-h ambulatory BP in 34 type 2 DN and 34 non-DN patients who were hospitalized for the educational program in our hospital. There were no significant differences in 24-h and daytime systolic BP between DN (143 vs. 136 mmHg, NS for 24-h systolic BP) and non-DN (143 vs. 138 mmHg, NS for daytime systolic BP). Although both groups disclosed blunted nocturnal decrease in BP and were classified as "non-dipper" type, DN patients had a significantly higher nighttime systolic BP than patients with non-DN (142 vs. 132 mmHg, p = 0.0217). BP and heart rate (HR) variabilities were also estimated, and patients with DN showed a reduced nighttime HR variability than those with non-DN (4.8 vs. 6.6 beats/min, p = 0.0115). DN patients had an increase in urinary protein excretion (3.0 vs. 1.4 g/day, p = 0.0095) and a decrease in serum albumin concentration (3.1 vs. 3.7 mg/dl, p < 0.0001). Furthermore, urinary protein excretion was significantly correlated with nighttime systolic BP (r = 0.480, p = 0.0031) but not with nighttime HR variability. Taken together, these results demonstrate that the circadian rhythms of BP and HR are affected by underlying diseases and suggest that an elevated nighttime BP level may contribute to the enhanced urinary protein excretion in hypertensives with DN.

Evidence suggests a relationship between short-term blood pressure (BP) variability and cardiovascular target-organ damage. Although a blunted nocturnal decrease in BP and reduced heart rate variability have been shown to be associated with cardiovascular morbidity in diabetic patients, little information is available on short-term BP variability. In this study, short-term BP variability was assessed in 36 subjects with type 2 diabetes and overt nephropathy who underwent ambulatory BP monitoring, and the factors that correlated with short-term BP variability were examined. The incidence of coronary artery disease (CAD) was significantly greater in the patients with increased 24-h systolic BP variability (67% versus 11%; p < 0.0005), while that of cerebrovascular disease was not significantly affected (61% versus 50%). Multiple stepwise regression analysis revealed that serum cholesterol (cholesterol) and plasma norepinephrine (p-NE) were significant and independent contributors to nighttime systolic BP variability (partial R2 = 0.490, p < 0.001; partial R2 = 0.470, p < 0.001) and demonstrated that body mass index and p-NE were primary determinants of nighttime diastolic BP variability (partial R2 = 0.539, p < 0.0005; partial R2 = 0.304, p < 0.05). Diabetic nephropathy patients with CAD had significantly increased daytime systolic (17.8 mmHg versus 13.1 mmHg, p < 0.0005), nighttime systolic (17.4 mmHg versus 10.5 mmHg, p < 0.0001), and nighttime diastolic (10.4 mmHg versus 7.2 mmHg, p < 0.05) BP variability. Furthermore, logistic regression analysis demonstrated that nighttime systolic BP variability was an independent risk factor for CAD (odds ratio 3.13 [95% CI 1.02-9.61]; p < 0.05). The increase in nighttime BP variability is associated with a proportional sympathetic activation in diabetic nephropathy. Elevated short-term BP variability combined with relative sympathetic prevalence during the night might represent an important risk factor for cardiovascular events in the diabetic population.

Increased resting heart rate (HR) and increased sympathetic nervous activity are independent risk factors for cardiovascular disease. Recently, base heart rate (HRo: minimum stable HR during sleep) has been reported to relate to cardiac stroke volume and age. However, little is known about the relevance of HRo. The aim of our study was to evaluate how HRo is associated with HR variability (HRV), blood pressure and health-related quality of life (HRQOL) in healthy subjects. A total of 139 volunteers participated in this study that measured 24-hr HR, HRV, and blood pressure. HRo was estimated from the trendgram and the histogram of HR during the nighttime (sleep) period, and calculated as the 1% lowest value of its integral. HRQOL was assessed by Medical Outcome Study Short-Forum 36-Item Health Survey. Sympathetic nervous activity (ratio of low frequency to high frequency component: LF/HF) and parasympathetic nervous activity (high frequency component: HF) were calculated by ECG monitoring. HRo was positively correlated with 24-hr LF/HF and nighttime LF/HF. HRo was negatively correlated with 24-hr HF and nighttime HF. Moreover, HRo was positively correlated with the scores of social functioning and role-physical. Using multivariate analysis, HRo is related to LF/HF, body mass index, and the score of social functioning (HRQOL). HRo may be a useful indicator for assessing sympathetic nervous activity and HRQOL in normotensive healthy subjects.

Recent reports suggest the relationship of short-term blood pressure (BP) variability to cardiovascular target organ damage. In this study, short-term BP variability was assessed as the standard deviation of daytime and nighttime BP in 36 hospitalized patients with chronic renal failure (CRF) who underwent ambulatory BP monitoring. Positive correlations were observed between body mass index (BMI) and daytime systolic and diastolic BP variability, BMI and nighttime diastolic BP variability, cholesterol and daytime systolic BP variability, cholesterol and nighttime systolic and diastolic BP variability, nocturnal decline in BP and nighttime diastolic BP variability, and plasma concentration of norepinephrine (p-NE) and nighttime systolic BP variability. In multivariate linear regression analyses, BMI showed the strongest association with daytime and nighttime diastolic BP variability (p < .005 and p < .05). On the other hand, cholesterol and p-NE were the primary determinants of daytime and nighttime systolic BP variability, respectively (p < .01 and p < .0005). Interestingly, CRF patients with ischemic heart disease (IHD) had significantly increased daytime systolic and diastolic BP variability and nighttime systolic BP variability (p < .05 or less). Furthermore, logistic regression analysis demonstrated that nighttime systolic BP variability was an independent risk factor of IHD in patients with CRF (odds ratio 1.50 [95% confidence interval 1.01 to 2.25]; p < .05). Taken together, short-term BP variability is suggested to be affected by BMI, cholesterol, and p-NE in CRF patients. Furthermore, sympathetic nerve overactivity may be involved in cardiovascular complications in CRF patients through the increase in nighttime systolic BP variability.

The aim of this study is to clarify the associations between diurnal blood pressure variation, physical activity and health-related quality of life (HRQOL). Ninety-seven volunteers, including 52 hypertensive patients and 45 healthy subjects (average age, 48 years) participated in this study. Twenty-four hour ambulatory blood pressure and heart rate variability were measured using TM2425 (A&D Co). Physical activity was measured using actigraphy, and HRQOL was assessed by a Medical Outcome Study Short-Forum 36-Item Health Survey (SF-36). Awake mean physical activity positively correlated with the nocturnal dip in systolic blood pressure (SBP) (r = 0.242, p < 0.02) and diastolic blood pressure (DBP) (r = 0.219, p < 0.04). The score of physical functioning positively correlated with awake mean physical activity (r = 0.265, p < 0.02). The score of role-emotional also correlated with awake mean physical activity (r = 0.269, p = 0.01). Using multiple regression analysis, the nocturnal dip in SBP was found to be correlated with awake and sleep mean physical activities (p < 0.05, p < 0.05, respectively). In conclusion, physical activity is associated with the nocturnal dip in blood pressure. Moreover, physical activity correlates with some of the factors of HRQOL.