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Background: Diuresis is a major therapy for the reduction of congestive symptoms in acute decompensated heart failure (ADHF) patients. We previously reported the efficacy and safety of tolvaptan compared to carperitide in hospitalized patients with ADHF. There were some reports of cardio- and renal-protective effects in carperitide; therefore, the purpose of this study was to compare the long-term effects of tolvaptan and carperitide on cardiorenal function and prognosis., Methods and Results: One hundred and five ADHF patients treated with either tolvaptan or carperitide were followed after hospital discharge. Levels of plasma B-type natriuretic peptide, serum sodium, potassium, creatinine, and estimated glomerular filtration rate were measured before administration of tolvaptan or carperitide at baseline, the time of discharge, and one year after discharge. These data between tolvaptan and carperitide groups were not different one year after discharge. Kaplan-Meier survival curves demonstrated that the event-free rate regarding all events, cardiac events, all cause deaths, and rehospitalization due to worsening heart failure was not significantly different between tolvaptan and carperitide groups., Conclusions: We demonstrated that tolvaptan had similar effects on cardiac and renal function and led to a similar prognosis in the long term, compared to carperitide.

Targeting the unique glioma immune microenvironment is a promising approach in developing breakthrough immunotherapy treatments. However, recent advances in immunotherapy, including the development of immune checkpoint inhibitors, have not improved the outcomes of patients with glioma. A way of monitoring biological activity of immune cells in neural tissues affected by glioma should be developed to address this lack of sensitivity to immunotherapy. Thus, in this study, we sought to examine the feasibility of non-invasive monitoring of glioma-associated microglia/macrophages (GAM) by utilizing our previously developed induced microglia-like (iMG) cells. Primary microglia (pMG) were isolated from surgically obtained brain tissues of 22 patients with neurological diseases. iMG cells were produced from monocytes extracted from the patients peripheral blood. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) revealed a significant correlation of the expression levels of representative markers for M1 and M2 microglia phenotypes between pMG and the corresponding iMG cells in each patient (Spearmans correlation coefficient = 0.5225, P

Study Design: Retrospective cohort study. Objectives: Intraspinal solitary fibrous tumor (SFT)/hemangiopericytoma (HPC) is often misdiagnosed preoperatively as schwannoma or meningioma because its imaging characteristics are not well understood. As postoperative prognosis differs among the 3 lesions, predicting the probability of SFT/HPC preoperatively is essential. Thus, this study investigates the imaging characteristics of SFT/HPC compared with those of schwannoma or meningioma and evaluates surgical outcomes. Methods: The preoperative imaging findings, tumor resection extent, recurrence and regrowth rates, and neurological improvement were compared between 10 patients with SFT/HPC and 42 patients with schwannoma or 40 patients with meningioma. Results: Most patients with SFT/HPC showed isointensity on both T1- and T2-weighted images compared with patients with schwannoma (P = 0.011 and 0.029, respectively) and no significant difference compared with patients with meningioma (P = 0.575 and 0.845, respectively). Almost all patients with SFT/HPC showed highly uniformizing enhancement patterns, similar to those with meningioma (P = 0.496). Compared with meningioma, SFT/HPC lacked the dural tail sign and intratumoral calcification and exhibited irregular shape. Of the 5 patients who underwent partial resection, 60% exhibited tumor recurrence and regrowth following surgery. Conclusions: Complete en bloc surgical resection should be attempted in patients with intraspinal SFT/HPC to prevent postoperative recurrence or regrowth. As this tumor is often preoperatively misdiagnosed, we recommend that the imaging findings exhibited in this study should be used to positively suspect SFT/HPC. This will enhance patient outcomes by enabling more appropriate preoperative surgical planning. [ABSTRACT FROM AUTHOR]

Background: The nationwide registry of the Japanese Gastric Cancer Association collected data of surgically resected cases of gastric cancer between 2001 and 2013. These retrospective analyses aimed to delineate tumor characteristics, surgical history, and survival distribution. Methods: Data from 254,706 patients with primary gastric cancer were included. The 5-year survival rates were calculated for various subsets of prognostic factors. Results: The number of patients over 70 years old increased from 2001 to 2013. The frequency with which laparoscopic gastrectomy was opted for increased dramatically (from 3.5 to 40.8%) in 13 years. We focused on the patients registered between 2010 and 2013, for whom data collection was based on the 3rd edition of the Japanese classification and guidelines. Five-year overall survival (OS) rate among 92,305 patients with resected tumors was 70.6%. The 5-year OS rates of patients with pathological stage IA, IB, IIA, IIB, IIIA, IIIB, IIIC, and IV disease were 89.6%, 83.2%, 77.6%, 68.1%, 59.3%, 45.6%, 29.9%, and 14.0%, respectively. Conclusion: Our detailed analysis highlights the historical changes in outcomes of surgically treated gastric malignancies in Japan, and provides robust dataset for future analysis. [ABSTRACT FROM AUTHOR]

Although intravenous diuretics is a cornerstone of acute heart failure treatment (AHF), its optimal initial dose is unclear. This is a post-hoc analysis of the REALITY-AHF, a prospective multicentre observational registry of AHF. The initial intravenous diuretic dose used in each patient was categorised into below, standard, or above the recommended dose groups according to guideline-recommended initial intravenous diuretic dose. The recommended dose was individualised based on the oral diuretic dose taken at admission. We compared the study endpoints, including 60-day mortality, diuretics response within six hours, and length of hospital stay (HS). Of 1093 patients, 429, 558, and 106 were assigned to the Below, Standard, and Above groups, respectively. The diuretics response and HS were significantly greater in the Below group than in the Standard group after adjusting for covariates. Kaplan–Meier analysis indicated a significantly higher incidence of 60-day mortality in the Above group than the Standard group. This difference was retained after adjusting for other prognostic factors. Treatment with a lower than guideline-recommended intravenous diuretic dose was associated with longer HS, whereas above the guideline-recommended dose was associated with a higher 60-day mortality rate. Our results reconfirm that the guideline-recommended initial intravenous diuretic dose is feasible for AHF. [ABSTRACT FROM AUTHOR]

Background: Chemonucleolysis with condoliase, which degrades chondroitin sulfate, could be a new, minimally invasive therapeutic option for patients with lumbar disc herniation (LDH). The purpose of this study was to analyze prognostic factors for clinical outcomes in LDH patients subjected to chemonucleolysis with condoliase.Methods: Inclusion criteria for this procedure were 1) 18-70 years of age; 2) unilateral leg pain and positive straight leg raise (SLR) (<70°) or femoral nerve stretching test; 3) subligamentous extrusion verified on magnetic resonance imaging; 4) neurological symptoms consistent with a compressed nerve root on magnetic resonance imaging (MRI) images; and 5) minimum six months of follow-up. In total, 82 patients (55 men, 27 women; mean age, 47.2 ± 15.5 years; mean follow-up, 9.1 ± 3.0 months) who underwent chemonucleolysis with condoliase for painful LDH were included. An improvement of 50% or more in the Visual analogue scale (VAS) of leg pain was classified as effective.Results: Seventy patients (85.4%) were classified into the effective (E) group and 12 patients (14.6%) into the less-effective (L) group. Surgical treatment was required in four patients. No severe adverse complications were reported; 41.3% of the patients developed disc degeneration of Pfirrmann grade 1 or more at the injected disc level. Univariate analysis revealed that young age (p = 0.036), without history of epidural or nerve root block (p = 0.024), and injection into the central portion of the intervertebral disc (p = 0.014) were significantly associated with clinical effectiveness. A logistic regression analysis revealed that injection into the central portion of the intervertebral disc (p = 0.049; odds ratio, 4.913; 95% confidence interval, 1.006-26.204) was significantly associated with clinical effectiveness.Conclusions: Chemonucleolysis with condoliase is a safe and effective treatment for painful LDH; 85.4% of the patients showed improvement after the treatment without severe adverse events. To obtain the best outcome, condoliase should be injected into the center of the intervertebral disc. [ABSTRACT FROM AUTHOR]

Aim: Total lymphocyte count in preoperative peripheral blood is associated with prognosis in various cancers. The predictive value of preoperative total lymphocyte count for survival was assessed in older gastric cancer patients after gastrectomy. Methods: A total of 200 gastric cancer patients aged ≥75 years who underwent curative resection from 2000 to 2014 were included in this retrospective study. The cut‐off value of total lymphocyte count in preoperative peripheral blood was determined using receiver operating characteristic curve analysis, and the association with prognosis was examined. Results: The cut‐off value of total lymphocyte count was 1462/μL, and 94 patients were classified as low total lymphocyte count patients and 106 patients were classified as high total lymphocyte count patients. In univariate analysis, American Society of Anesthesiologists score ≥3, Charlson Comorbidity Index ≥3, total lymphocyte count <1462/μL, stage III, open approach, total gastrectomy, splenectomy and infectious complication were significantly associated with overall survival. In multivariate analysis, total lymphocyte count <1462/μL (P = 0.003), American Society of Anesthesiologists score ≥3 (P = 0.01) and stage III (P = 0.017) were independent prognostic factors. Low total lymphocyte count significantly reduced overall survival in stage I (P = 0.037) and II (P = 0.009) patients, but not stage III patients (P = 0.29). Conclusion: Total lymphocyte count in preoperative peripheral blood can predict postoperative survival of older patients with relatively early‐stage gastric cancer. Geriatr Gerontol Int 2019; 19: 1215–1219. [ABSTRACT FROM AUTHOR]

Background: Prognostication of patients discharged after acute heart failure (AHF) hospitalization remains challenging. Body weight (BW) reduction is often used as a surrogate marker of decongestion despite the paucity of evidence. We thought to test the hypothesis that B-type natriuretic peptide (BNP) reduction during hospitalization has independent prognostic value in AHF.Methods and Results: We studied the prognostic predictability of percentage BNP reduction achieved during hospitalization in patients from the REALITY-AHF study. Percentage BNP reduction was defined as (BNP on admission - BNP at discharge) / BNP on admission × 100. The primary endpoint was 1-year all-cause death. In 1028 patients (age, 77 ± 13 years; 57% male; left ventricular ejection fraction, 47 ± 16%) with AHF, median BNP level at admission was 747 ng/L (interquartile range, 439-1367 ng/L) and median percentage BNP reduction was 62.5% (interquartile range, 36.5-78.5%). The smallest percentage BNP reduction quartile had more than 2-fold higher risk of all-cause death than the greatest quartile (23.0% vs 9.7%, P< .001). After adjusting for covariates including BNP at discharge, the percentage BNP reduction was significantly associated with all-cause death (hazard ratio 0.96, 95% confidence interval 0.93-0.99, P= .032), whereas percentage BW reduction was not. Percentage BNP reduction was more predictive in patients with heart failure with reduced ejection fraction than in those with preserved ejection fraction.Conclusions: The prognostic value of percentage BNP reduction during hospitalization was superior to that of percentage BW reduction and was independent of other risk markers, including BNP at discharge. [ABSTRACT FROM AUTHOR]

Background: In hospitalized heart failure patients, a poor diuretic response (DR) during the first days of hospital admission is associated with worse outcomes. However, it remains unknown whether DR in the first hours has similar prognostic value. Moreover, data on the sequential change in DR during hospital admission are lacking.Methods and Results: DR (urine output per 40-mg furosemide-equivalent diuretics dose) was measured from 0 to 6 hours (DR6), 6 to 48 hours (DR6-48), and 0 to 48 hours (DR48) of the patient's emergency department (ED) arrival in 1551 patients with acute heart failure (AHF; mean age 78 years, 56% male, and 48% de novo patients with heart failure). Patients with a poor DR within the first 6 hours were older age, had worse renal function, and were already on diuretic treatment before admission. DR6 was only weakly correlated with DR6-48 (Spearman's rho = 0.273; P < .001). DR6, DR6-48, and DR48 were all significantly associated with 60-day mortality independent of other prognostic factors. DR6 and DR48 showed comparable prognostic ability. However, the model combining DR6 with DR6-48 significantly exceeded both DR6 (net reclassification improvement 0.249; P = .032) and DR48 (net reclassification improvement 0.287; P = 0.025) with regard to 60-day mortality prediction.Conclusions: DR measured within the first 6 hours of ED arrival and DR measured during the first 48 hours in patients with AHF have similar prognostic value, although they were moderately correlated. Changes in DR over time provide additional prognostic information. [ABSTRACT FROM AUTHOR]

Background: Zinc is an essential cofactor for energy transfer and physiological heart function, has antioxidant properties, and is involved in multiple signaling pathways. We aimed to investigate the associations between serum zinc levels with prognosis, as well as underlying cardiac function and exercise capacity, in patients with heart failure (HF).Methods and Results: We measured serum zinc levels in 968 consecutive hospitalized patients with decompensated HF, who were divided into 3 groups based on serum zinc levels (µg/dL): first (zinc ≥75, n = 323), second (62≤ zinc <75, n = 322), and third (zinc <62, n = 323) tertiles. We examined cardiac function and exercise capacity and followed up on all patients. Although cardiac function did not differ among the 3 groups, peak oxygen consumption was significantly lower in the third tertile than in the first and second tertiles (peak oxygen consumption, 14.2 vs 15.9 and 15.2 mL/kg/min, P = .010). In the Kaplan-Meier analysis (mean duration of follow-up 1103 days), cardiac and all-cause mortality was highest in the third tertile compared with the first and second tertiles. In the Cox proportional hazard analysis, serum zinc level was a predictor of cardiac and all-cause mortality. In the subgroup analysis, there were no interactions concerning associations between serum zinc levels with prognosis and other important variables, including age, gender, comorbidities, medications, other micronutrient levels, B-type natriuretic peptide, and left ventricular ejection fraction. The associations between zinc levels with mortality were consistent in all subgroups.Conclusion: Decreased serum zinc levels are associated with high mortality, accompanied by impaired exercise capacity. [ABSTRACT FROM AUTHOR]

Isocitrate dehydrogenase ( IDH) mutation is a good prognostic marker for glioblastoma (GBM). Although it is infrequent in primary tumors, it is found in most lower-grade gliomas. Thus, it is unclear whether IDH mutation is a marker for a specific phenotype of apparently primary de novo GBMs (pGBMs), or a marker for secondary tumors (sGBMs). We addressed this issue by analyzing clinical, radiographic and molecular findings in our institutional case series. Our cases included 92 pGBMs, with five cases of IDH1 mutations at R132 and no IDH2 mutations. The median overall survival of these five patients was 29 months (range: 4 to >40 months), which is considered good prognoses. Clinical and radiographic characteristics were distinct from IDH-wildtype ( IDH-wt) pGBMs. IDH-mutant ( IDH-mut) tumors consistently involved insular lesions and were subdivided into: (i) the two cases of elderly patients with long clinical histories and features implying multistep tumor development; and (ii) the three cases of younger patients with diffusely swelling insular tumors, slight contrast enhancement and no necrosis. Genetic and expression analyses of IDH-mut pGBMs were similar to those of sGBMs, suggesting that they are indeed distinct from their IDH-wt counterparts. TERT promoter mutation, a genetic marker of oligodendroglial derivation, was detected in one long-surviving case, but genetic alterations in the astrocyte-sGBM pathway were generally prevalent in IDH-mut pGBMs. Our results present a unique phenotype of IDH-mut pGBMs arising from insular cortex region, the molecular backgrounds of which are similar to sGBMs. [ABSTRACT FROM AUTHOR]

Background: Effective treatments in heart failure (HF) patients with ischemic etiology have not been fully established. Nicorandil, combination of nitrate component and sarcolemmal adenosine triphosphate-sensitive potassium channel opener, is a potent vasodilator of coronary and peripheral vessels and has been used as an antianginal agent. Therefore, we examined impacts of nicorandil on cardiac mortality in ischemic HF patients.Methods: Consecutive 334 HF patients with ischemic etiology were retrospectively registered and divided into 2 groups based on oral administration of nicorandil: nicorandil group (n = 116) and non-nicorandil group (n = 218). We retrospectively examined cardiac mortality.Results: In the Kaplan-Meier analysis (mean follow-up period 963 days), cardiac mortality was significantly lower in the nicorandil group than in the non-nicorandil group (11.2% vs. 19.7%, P = 0.032). In the Cox proportional hazard analysis, usage of nicorandil was a suppressor of cardiac mortality (hazard ratio 0.512, 95% confidence interval 0.275-0.953, P = 0.035), and this result was consistent in several subgroup analyses, such as left ventricular ejection fraction, percutaneous coronary intervention, coronary artery bypass graft, diabetes, β-blockers, and statins.Conclusion: Nicorandil is potentially effective for reducing mortality in patients with ischemic heart failure.Trial Registration: This was a retrospective study. [ABSTRACT FROM AUTHOR]

Background: The feasibility and efficacy of adjuvant hepatic arterial infusion (HAI) in preventing the development of liver metastases in patients with advanced colon carcinoma have not been validated. The aim of this randomized controlled study was to compare the feasibility of HAI and the protective effect against liver metastasis after curative resection to those of systemic chemotherapy.Methods: Between July 2000 and June 2003, 91 patients were enrolled. Patients were randomly assigned to receive 5-fluorouracil (5-FU) via continuous venous infusion (CVI) or intra-hepatic arterial weekly high-dose 5-FU (WHF). The primary endpoint was overall survival (OS).Results: In the WHF group, the cumulative failure rate of hepatic arterial catheterization was 16.7% at 6 months. The occurrence of grade 3 adverse events was comparable between the groups. The 5-year OS rates were 59.0% in the CVI group and 34.9% in the WHF group (P = 0.164). CVI tended to show a protective effect against liver metastasis regarding the 5-year liver-specific cumulative recurrence rate: CVI, 45.0% vs. WHF, 68.3%; P = 0.037).Conclusion: HAI therapy has a certain protective effect against liver metastasis after curative resection in patients with colorectal cancer. However, this therapy did not contribute to any marked improvement in their overall survival. [ABSTRACT FROM AUTHOR]

Background: Intake of n-3 polyunsaturated fatty acids (n-3 PUFAs) lowers the risk of atherosclerotic cardiovascular events, particularly ischemic heart disease. In addition, the ratio of eicosapentaenoic acid (EPA; n-3 PUFA) to arachidonic acid (AA; n-6 PUFA) has recently been recognized as a risk marker of cardiovascular disease. In contrast, the prognostic impact of the EPA/AA ratio on patients with heart failure (HF) remains unclear.Methods and Results: A total of 577 consecutive patients admitted for HF were divided into 2 groups based on median of the EPA/AA ratio: low EPA/AA (EPA/AA <0.32 mg/dl, n = 291) and high EPA/AA (EPA/AA ≥0.32, n = 286) groups. We compared laboratory data and echocardiographic findings and followed cardiac mortality. Although body mass index, blood pressure, B-type natriuretic peptide, hemoglobin, estimated glomerular filtration rate, total protein, albumin, sodium, C-reactive protein, and left ventricular ejection fraction did not differ between the 2 groups, cardiac mortality was significantly higher in the low EPA/AA group than in the high EPA/AA group (12.7 vs 5.9%, log-rank P = .004). Multivariate Cox proportional hazard analysis revealed that the EPA/AA ratio was an independent predictor of cardiac mortality (hazard ratio 0.677, 95% confidence interval 0.453-0.983, P = .041) in patients with HF.Conclusion: The EPA/AA ratio was an independent predictor of cardiac mortality in patients with HF; therefore, the prognosis of patients with HF may be improved by taking appropriate management to control the EPA/AA balance. [ABSTRACT FROM AUTHOR]

Background: Preoperative chemoradiotherapy (CRT) is widely used in the treatment of locally advanced rectal cancer (LARC). Pathological response to CRT has been shown to be a potential prognostic predictor in rectal cancer patients. The aim of this study was to determine the prognostic significance of pathological response to preoperative CRT in LARC patients. Methods: Thirty-two patients with LARC were retrospectively analyzed to determine the relationships of pathological response and clinicopathological characteristics to survival outcomes. Patients received CRT with tegafur/uracil and leucovorin. Radiotherapy was administered in fractions of 1.8 Gy/day and 5 days per week. The total dose of radiation delivered was 45 Gy. Results: All patients underwent total mesorectal excision with lymph node dissections after CRT, and resected specimens were examined pathologically. Four patients showed pathological complete response, 14 showed good response, and 14 showed poor response. Pathological complete or good response was associated with longer survival ( P = 0.041). Clinicopathological factors excluding gender were not correlated with outcome. No factor was associated with recurrence. Conclusion: Pathological response to preoperative CRT may be a useful prognostic predictor in patients with LARC. [ABSTRACT FROM AUTHOR]

The inflammation-based modified Glasgow prognostic score ( mGPS) has been shown to be a prognostic factor for esophageal cancer, but its changes in relation to neoadjuvant chemotherapy ( NAC) have never been discussed. The purpose of this study was to evaluate the potential prognostic role of mGPS with regard to NAC. mGPS was evaluated on the basis of admission blood samples taken before chemotherapy and before surgery. Patients with elevated C-reactive protein ( CRP) serum levels (>10 mg/L) and hypoalbuminemia (<35 g/L) were allocated a score of 2, patients with elevated CRP serum levels without hypoalbuminemia were allocated a score of 1, and patients with normal CRP serum levels with or without hypoalbuminemia were allocated a score of 0. A total of 100 patients with clinical stage II/ III squamous cell esophageal cancer, who underwent NAC and esophagectomy between January 2007 and August 2012, were investigated. From the multivariate analysis, the grade of response to chemotherapy and post- NAC mGPS level was found to be independent prognostic factors. The overall survival rate was significantly higher in the conserved mGPS group than in the worse mGPS group ( P = 0.030). Changes in mGPS during chemotherapy affected the prognosis of patients, and post- NAC mGPS is an independent prognostic factor in patients with clinical stage II/ III thoracic esophageal squamous cell cancer. [ABSTRACT FROM AUTHOR]

Background Chronic kidney disease–mineral and bone disorders (CKD-MBD) are associated with vascular calcification and abnormal electrolytes that lead to cardiovascular disease and mortality. CKD-MBD is identified by imbalances in serum calcium (Ca), phosphate, and parathyroid hormone (PTH). Although the relation of phosphate and PTH with the prognosis of HF patients has been reported, the association of Ca with prognosis in patients with heart failure (HF) and CKD remains unclear. Methods and Results We examined 191 patients admitted for HF and CKD (estimated glomerular filtration rate <60 mL min −1 1.73 m −2 ), and they were divided into 2 groups based on levels of corrected Ca: low Ca (Ca <8.4 mg/dL; n = 32) and normal-high Ca (8.4 ≤Ca; n = 159). We compared laboratory and echocardiographic findings, as well as followed cardiac and all-cause mortality. The low-Ca group had 1) higher levels of alkaline phosphatase (308.9 vs 261.0 U/L; P = .026), 2) lower levels of 1,25-dihydroxy vitamin D (26.1 vs 45.0 pg/mL; P = .011) and hydrogen carbonate (22.4 vs 24.5 mmol/L; P = .031), and 3) a tendency to have a higher PTH level (87.5 vs 58.6 pg/mL; P = .084). In contrast, left and right ventricular systolic function, estimated glomerular filtration rate, urine protein, phosphate, sodium, potassium, magnesium, and zinc did not differ between the 2 groups. In the Kaplan-Meier analysis, cardiac and all-cause mortality were significantly higher in the low-Ca group than in the normal-high–Ca group ( P < .05). In the multivariable Cox proportional hazard analyses, hypocalcemia was an independent predictor of all-cause mortality in HF and CKD patients ( P < .05). Conclusions Hypocalcemia was an independent predictor of all-cause mortality in HF and CKD patients. [ABSTRACT FROM AUTHOR]

Aim The purpose in the present study was to compare prognostic risk factors between older and younger chronic heart failure ( CHF) patients. Methods We examined 598 consecutive CHF patients (476 men and 122 women, mean age 61.4 ± 14.3 years) who underwent cardiopulmonary exercise testing, echocardiography and blood examination. We divided the 598 patients into two groups: the elderly group (age ≥75 years, n = 123) and the young group (age <75, n = 475). We compared blood testing data, exercise capacity, cardiac function and prognosis between the two groups. Patients were followed up (median 782 days) to register cardiac deaths or rehospitalization as a result of worsening heart failure. Results Patients in the elderly group were associated with higher frequencies of atrial fibrillation and diuretic use than those in the young group. Patients in the elderly group had lower hemoglobin concentration, more impaired renal function, higher plasma B-type natriuretic peptide ( BNP) levels, smaller left ventricular volume, longer deceleration time of early mitral wave and lower exercise capacity than those in the young group. There were 199 cardiac events during follow-up periods. As expected, Kaplan- Meier analysis showed that patients in the elderly group had higher cardiac event rates than those in the young group. In the young group, multivariable Cox hazard analysis showed that hemoglobin concentration, log BNP and peak VO2 were independent predictors related to cardiac events. In contrast, in the elderly group, estimated glomerular filtration rate, atrial fibrillation and peak VO2 were independent factors to predict adverse clinical outcomes. Conclusions Prognostic factors were different between the elderly and young patients in CHF. Geriatr Gerontol Int 2015; 15: 435-442. [ABSTRACT FROM AUTHOR]

Aims: Liver dysfunction due to heart failure (HF) is often referred to as cardiac or congestive hepatopathy. The composite Model for End-Stage Liver Disease excluding INR (MELD-XI) is a robust scoring system of liver function, and a high score is associated with poor prognosis in advanced HF patients with a heart transplantation and/or ventricular assist device. However, the impact of MELD-XI on the prognosis of HF patients in general remains unclear. Methods and Results: We retrospectively analyzed 562 patients who were admitted to our hospital for the treatment of decompensated HF. A MELD-XI score was graded, and patients were divided into two groups based on the median value of MELD-XI score: Group L (MELD-XI <10, n = 289) and Group H (MELD-XI ≥10, n = 273). We compared all-cause mortality and echocardiographic findings between the two groups. In the follow-up period (mean 471 days), 104 deaths (62 cardiac deaths and 42 non-cardiac deaths) were observed. The event (cardiac death, non-cardiac death, all-cause death)-free rate was significantly higher in group L than in group H (logrank P<0.05, respectively). In the Cox proportional hazard analysis, a high MELD-XI score was found to be an independent predictor of cardiac deaths and all-cause mortality in HF patients. Regarding echocardiographic parameters, right atrial and ventricular areas, inferior vena cava diameter, and systolic pulmonary artery pressure were higher in group H than in group L (P<0.05, respectively). Conclusions: The MELD-XI scoring system, a marker of liver function, can identify high-risk patients with right heart volume overload, higher pulmonary arterial pressure and multiple organ failure associated with HF. [ABSTRACT FROM AUTHOR]

Sleep-disordered breathing (SDB) deteriorates the prognosis of patients with chronic heart failure (CHF). Adaptive servo ventilation (ASV) is a new therapeutic modality to treat SDB including Cheyne–Stokes respiration associated with central sleep apnea. Renal function plays critical roles in the progression of CHF and is a strong predictor of clinical outcomes. Cystatin C is a marker of renal function, and more sensitive than serum creatinine. The purpose of the present study was to examine whether ASV is effective for cardiac overload and renal dysfunction in CHF patients with SDB. Fifty patients with CHF and SDB (mean left ventricular ejection fraction 34.0 %, estimated glomerular filtration rate (eGFR) 62.8 ml/min/1.73 cm 2) were examined. We performed polysomnography for two consecutive days (baseline and on ASV), and measured levels of serum N terminal-pro B-type natriuretic peptide (NT-pro BNP), cystatin C, and estimated glomerular filtration rate based on cystatin C (eGFR Cyst C). ASV significantly improved the apnea hypopnea index, central apnea index, obstructive apnea index, arousal index, mean SPO 2, and lowest SPO 2 compared to baseline. ASV decreased NT-pro BNP (1,109.0 (2,173.2) to 912.8 (1,576.7) pg/ml, p < 0.05), cystatin C (1.391 ± 0.550–1.348 ± 0.489 mg/l, p < 0.05), and increased eGFR Cyst C (61.9 ± 30.8–65.7 ± 33.8 ml/min/1.73 cm 2, p < 0.01). ASV improved SDB, reduced cardiac overload, and ameliorated renal function in CHF patients with SDB. ASV has short-term beneficial effects on not only SDB but also cardio-renal function. ASV might be a promising useful tool for CHF as an important non-pharmacotherapy with cardio-renal protection. [ABSTRACT FROM AUTHOR]

Aims Effective pharmacotherapy for heart failure with preserved left ventricular ejection fraction (HFpEF) is still unclear. Sleep-disordered breathing (SDB) causes cardiovascular dysfunction, giving rise to factors involved in HFpEF. However, it remains unclear whether adaptive servo-ventilation (ASV) improves cardiovascular function and long-term prognosis of patients with HFpEF and SDB. Methods and results Thirty-six patients with HFpEF (LVEF >50%) and moderate to severe SDB (apnoea–hypopnoea index >15/h) were enrolled. Study subjects (LVEF 56.0%, apnoea–hypopnoea index 36.5/h) were randomly assigned to two groups: 18 patients treated with medications and ASV (ASV group) and 18 patients not treated with ASV (non-ASV group). NYHA class, cardiac function including LVEF, left atrial volume index (LAVI), E/E', vascular function including flow-mediated dilatation (FMD) and cardio-ankle vascular index (CAVI), and levels of BNP and troponin T were determined at baseline and 6 months later. Patients were followed to register cardiac events after enrolment (follow-up 543 days). ASV therapy improved cardiac diastolic function and decreased CAVI and BNP (NYHA class, 2.3 to 1.5; LAVI, 48.6 to 42.6 mL/m2; E/E', 12.8 to 7.1; CAVI, 9.0 to 7.7; BNP, 121.5 to 58.1 pg/mL, P < 0.0125, respectively). LVEF, FMD, and troponin T did not change significantly in either group. Importantly, the event-free rate was significantly higher in the ASV group than in the non-ASV group (94.4% vs. 61.1%, log-rank P < 0.05). Conclusion ASV may improve the prognosis of HFpEF patients with SDB, with favourable effects such as improvement of symptoms, cardiac diastolic function, and arterial stiffness. ASV may be a useful therapeutic tool for HFpEF patients with SDB. [ABSTRACT FROM PUBLISHER]

Abstract: Background: Chronic kidney disease (CKD) and sleep-disordered breathing (SDB) play critical roles in the progression of chronic heart failure (CHF). However, it still remains unclear whether adaptive servoventilation (ASV) improves cardiorenal function and the prognosis of CHF patients with CKD and SDB. Methods and Results: Eighty CHF patients with CKD (estimated glomerular filtration rate of <60 mL min−1 1.73 cm−2) and SDB (apnea-hypopnea index >15/h) were enrolled and divided into 2 groups: 36 patients were treated with usual care plus ASV (ASV group) and 44 patients were treated with usual care alone (Non-ASV group). Levels of B-type natriuretic peptide, glomerular filtration rate, cystatin C, C-reactive protein, noradrenaline, and left ventricular ejection fraction were measured before treatment and 6 months after treatment. Patients were followed to register cardiac events occurring after enrollment. Six months of ASV therapy reduced levels of B-type natriuretic peptide, cystatin C, C-reactive protein, and noradrenaline and improved the glomerular filtration rate and ejection fraction (all P < .05). However, none of these parameters changed in the Non-ASV group. Thirty-two events (14 deaths and 18 rehospitalizations) occurred during the follow-up period (mean 513 days). Importantly, the event-free rate was significantly higher in the ASV group than in the Non-ASV group (77.8% vs 45.5%; log rank P < .01). Conclusions: ASV improves the prognosis of CHF patients with CKD and SDB, with favorable effects such as the improvement of cardiorenal function and attenuation of inflammation and sympathetic nervous activity. [Copyright &y& Elsevier]

Background: Cheyne-Stokes respiration (CSR-CSA) is often observed in patients with chronic heart failure (CHF). Although cardiac resynchronization therapy (CRT) is effective for CHF patients with left ventricular dyssynchrony, it is still unclear whether adaptive servo ventilation (ASV) improves cardiac function and prognosis of CHF patients with CSR-CSA after CRT. Methods and results: Twenty two patients with CHF and CSR-CSA after CRT defibrillator (CRTD) implantation were enrolled in the present study and randomly assigned into two groups: 11 patients treated with ASV (ASV group) and 11 patients treated without ASV (non-ASV group). Measurement of plasma B-type natriuretic peptide (BNP) levels (before 3, and 6 months later) and echocardiography (before and 6 months) were performed in each group. Patients were followed up to register cardiac events (cardiac death and re-hospitalization) after discharge. In the ASV group, indices for apnea-hypopnea, central apnea, and oxyhemoglobin saturation were improved on ASV. BNP levels, cardiac systolic and diastolic function were improved with ASV treatment for 6 months. Importantly, the event-free rate was significantly higher in the ASV group than in the non-ASV group. Conclusions: ASV improves CSR-CSA, cardiac function, and prognosis in CHF patients with CRTD. Patients with CSR-CSA and post CRTD implantation would get benefits by treatment with ASV. [ABSTRACT FROM AUTHOR]

Background DNA in the nucleus is one of the major targets of reactive oxygen species (ROS), and oxidative DNA damage has been implicated in the pathogenesis of chronic heart failure. 8-Hydroxy-2'-deoxyguanosine (8-OHdG) is produced from deoxyguanosine in DNA by ROS. The purpose of this present study was to examine the clinical significance of serum 8-OHdG levels in patients with heart failure. Methods We measured serum 8-OHdG levels in 230 patients with chronic heart failure and 42 control subjects without heart failure by sandwich enzyme-linked immunosorbent assay. Patients were prospectively followed during a median follow-up period of 472 days with the end points of cardiac death or progressive heart failure requiring re-hospitalization. Results Serum 8-OHdG concentrations were higher in patients with heart failure than in control subjects (P < 0·001) and increased with advancing New York Heart Association (NYHA) functional class (P < 0·001). Normal upper limit of 8-OHdG level was determined as mean ± 2SD value from 42 control subjects (0·40 ng mL-1). Abnormally high serum 8-OHdG levels (> 0·40 ng mL-1) were observed in 21·2%, 43·1%, 42·6% and 69·4% through NYHA I to IV (P < 0·001). A total of 66 cardiac events occurred during a follow-up period, and Kaplan- Meier survival curves demonstrated that cardiac event rate was markedly higher in patients with high 8-OHdG levels than in those with normal 8-OHdG levels (62·4% vs. 29·6%, P = 0·0007). Conclusions Serum 8-OHdG levels provide important prognostic information for the risk stratification of patients with heart failure. [ABSTRACT FROM AUTHOR]

Abstract: Background: Human cartilage glycoprotein-39 (YKL-40), a novel inflammatory marker, is secreted into circulation by macrophages, neutrophils, chondrocytes, vascular smooth muscle cells and cancer cells. Circulating levels of YKL-40 are related to the degree of inflammation, tissue remodeling, fibrosis, and cancer progression. Methods and Results: We examined serum YKL-40 levels in 121 patients with chronic heart failure (CHF) and 39 control subjects. The patients were followed up to register cardiac events for a mean of 720 days. Serum YKL-40 levels were measured by sandwich enzyme-linked immunoassay. Serum YKL-40 was significantly higher in New York Heart Association (NYHA) Class III/IV patients than control subjects and NYHA Class I/II patients (P < .0001). Serum YKL-40 was also higher in patients with cardiac events than in event-free patients (P = .0023). Cutoff value of YKL-40 was determined by receiver operating characteristic curve analysis. Kaplan-Meier analysis demonstrated that high level of YKL-40 was associated with higher rates of cardiac events than low levels of YKL-40 (P = .003). The multivariate Cox hazard analysis demonstrated that serum YKL-40 level was an independent prognostic factor of cardiac events (hazard ratio 2.085, 95% confidence interval 1.233-3.499, P < .0048). Conclusions: Serum YKL-40, a new marker of inflammation, was increased in CHF, and YKL-40 detected high risk patients for adverse outcomes in CHF. [Copyright &y& Elsevier]

Abstract: Background: Midkine, a heparin-binding growth factor, has various functions such as migration of inflammatory cell and anti-apoptotic effect. Invasion of inflammatory cell and cardiomyocyte apoptosis are involved in development and progression of heart failure (HF). However, the relationship between midkine and HF has not been previously examined. Therefore, we examined clinical significance of serum midkine levels to determine the prognosis of HF patients. Methods and Results: Serum levels of midkine were measured at admission in 216 consecutive patients hospitalized for HF and 60 control subjects. Patients were prospectively followed during a mean follow-up period of 653 ± 375 days with the end points of cardiac death and progressive HF requiring rehospitalization. Serum concentrations of midkine were significantly higher in patients with HF than in controls. Patients with cardiac events had significantly higher concentrations of midkine than those without cardiac events. Kaplan-Meier analysis revealed that cardiac event rates increased markedly as midkine levels rose. Furthermore in the multivariate analysis, after adjustment for age, gender ,and complications, midkine was the independent predictor of cardiac events. Conclusion: Serum midkine levels are increased in HF patients, and midkine is a novel marker for risk stratifying HF patients. [Copyright &y& Elsevier]

Summary: Background: Although there is substantial interest in the use of newer biomarkers to identify patients with chronic heart failure (CHF), recently few investigations have evaluated the incremental usefulness of multiple conventional biomarkers. Combination of several biomarkers simultaneously could enhance risk stratification in CHF. Methods and results: We analyzed 7 biomarkers (brain natriuretic peptide, uric acid, sodium, hemoglobin, creatinine, creatinine clearance, high-sensitivity C-reactive protein), which were known as established prognostic markers for CHF, in 154 consecutive CHF patients, and patients were prospectively followed with endpoints of cardiac death or re-hospitalization. When there was an abnormal value, we scored it for one point to calculate multimarker score. Patients were categorized into 3 strata according to multimarker score. There were 83 cardiac events during the follow-up period. A Cox proportional hazard model showed that patients in the high stratum were associated with the highest risk of cardiac events among the 3 strata. Kaplan–Meier analysis revealed that patients in the high stratum had a significantly higher cardiac event rate compared with lower strata. Conclusion: The combination of conventional biomarkers could potentially improve the risk stratification of CHF patients for the prediction of cardiac events with low cost and wide availability. [Copyright &y& Elsevier]

The article focuses on prognosis-predicting equations using histological scores contribute to the choice of steroid therapy in IgA nephropathy. An applicability of steroid therapy (ST) can be judged by comparing the probability from each predicting equation for PUP as well as for RFI in the group of ST with the correspondence in the group without ST. Multivariate logistic regression analysis was used to provide adjusted relative estimates for association between histological predictor variables and proteinuric progression.

Background: Although liver dysfunction is one of the common complications in patients with acute heart failure (AHF), no integrated marker has been defined. The albumin-bilirubin (ALBI) score has recently been proposed as a novel, clinically-applicable scoring system for liver dysfunction. We investigated the utility of the ALBI score in patients with AHF compared to that for a preexisting liver dysfunction score, the Model of End-Stage Liver Disease Excluding prothrombin time (MELD XI) score.Methods: We evaluated ALBI and MELD XI scores in 1,190 AHF patients enrolled in the prospective, multicentre Registry Focused on Very Early Presentation and Treatment in Emergency Department of Acute Heart Failure study. The associations between the two scores and the clinical profile and prognostic predictive ability for 1-year mortality were evaluated.Results: The mean MELD XI and ALBI scores were 13.4±4.8 and -2.25±0.48, respectively. A higher ALBI score, but not higher MELD XI score, was associated with findings of fluid overload. After adjusting for pre-existing prognostic factors, the ALBI score (HR 2.11, 95% CI: 1.60-2.79, p<0.001), but not the MELD XI score (HR 1.02, 95% CI: 0.99-1.06, p=0.242), was associated with 1-year mortality. Likewise, area under the receiver-operator-characteristic curves for 1-year mortality significantly increased when the ALBI score (0.71 vs. 0.74, p=0.020), but not the MELD XI score (0.71 vs. 0.72, p=0.448), was added to the pre-existing risk factors.Conclusions: The ALBI score is potentially a suitable liver dysfunction marker that incorporates information on fluid overload and prognosis in patients with AHF. These results provide new insights into heart-liver interactions in AHF patients. [ABSTRACT FROM AUTHOR]

The LHFRS is a simple score derived from three factors (history of hypertension, history of coronary artery disease/myocardial infarction, and red blood cell distribution width) deployed for the risk stratification of AHF in Greek population. This study aimed to validate the Larissa Heart Failure Risk Score (LHFRS) in patients with acute heart failure (AHF) in a Japanese population. We performed post-hoc analysis of 1670 consecutive patients enrolled in the REALITY-AHF. In all, 964 patients were finally enrolled. Exclusion criteria included patients with anemia, malignancies and sepsis. The primary outcome was defined as a composite of all-cause mortality and/or heart failure readmission, and the secondary outcome was defined as all-cause mortality. The median admission LHFRS value was 1 (interquartile range [IQR]: 0–2). During a median follow-up of 365 (IQR: 161–365) days, the primary and secondary outcomes were observed in 321 and 157 patients, respectively. LHFRS was an independent predictor of both the primary (adjusted hazard ratio per 1-point increase, 95% confidence interval: 1.17 [1.04–1.32], p = 0.011), and the secondary outcomes (1.31 [1.12–1.55], p = 0.001). Patients with higher LHFRS scores (≥2) exhibited significantly worse outcomes than those with lower scores (<2) both for the primary outcome (1.40 [1.07–1.83], p = 0.014) and the secondary outcome (1.60 [1.09–2.34], p = 0.015). Additionally, LHFRS revealed an excellent goodness of fit (observed versus predicted outcomes) for predicting both the primary and the secondary outcomes (p > 0.99 and p = 0.99, respectively). The simple LHFRS was proved as a reliable predictor of outcomes in patients with AHF. • Risk stratification is important during hospitalization for acute heart failure (AHF). • The Larissa Heart Failure Risk Score (LHFRS) is a simple score that easily and reliably risk stratifies AHF patients. • Close monitoring of high risk AHF patients is warranted. [ABSTRACT FROM AUTHOR]

Abstract Background C-reactive protein (CRP) has been reported to be associated with poorer prognosis in various malignancies. However, the relationship between CRP and differentiated thyroid carcinoma (DTC) remains to be elucidated. Methods A total of 45 patients, including 32 patients with preoperative DTC and 13 DTC patients with metastatic disease, were included in the study. The relationships between CRP levels and clinicopathological features were retrospectively analyzed. Results Analysis using a receiver operating characteristic curve revealed a preoperative CRP cutoff value of 0.155 mg/dL. Patients with preoperative CRP ≥ 0.155 mg/dL, those with T3 + T4, those with extrathyroidal invasion, or those with stage II, showed a statistically shorter recurrent-free survival than those with preoperative CRP < 0.155 mg/dL, those with T1 + T2, those without extrathyroidal invasion, or those with stage I (P = 0.001, P = 0.004, P = 0.024, and P = 0.025, respectively). Preoperative CRP ≥ 0.155 mg/dL was an independent prognostic factor for recurrent-free survival in the DTC patients (hazard ratio = 6.334, 95% confidence interval: 1.023-39.234, P = 0.037). The proportion of patients aged ≥55 y, and those with T3 + T4, was statistically higher in those with preoperative CRP ≥ 0.155 mg/dL than in those with preoperative CRP < 0.155 mg/dL (P = 0.037 and P = 0.038, respectively). Conclusions Higher preoperative CRP levels have a robust prognostic impact on recurrence-free survival in DTC patients. In addition, higher preoperative CRP levels were associated with age ≥ 55 y and T3 + T4. [ABSTRACT FROM AUTHOR]

Background: Acute heart failure (AHF) is a life-threatening disease requiring urgent treatment, including a recommendation for immediate initiation of loop diuretics.Objectives: The authors prospectively evaluated the association between time-to-diuretic treatment and clinical outcome.Methods: REALITY-AHF (Registry Focused on Very Early Presentation and Treatment in Emergency Department of Acute Heart Failure) was a prospective, multicenter, observational cohort study that primarily aimed to assess the association between time to loop diuretic treatment and clinical outcome in patients with AHF admitted through the emergency department (ED). Door-to-furosemide (D2F) time was defined as the time from patient arrival at the ED to the first intravenous furosemide injection. Patients with a D2F time <60 min were pre-defined as the early treatment group. Primary outcome was all-cause in-hospital mortality.Results: Among 1,291 AHF patients treated with intravenous furosemide within 24 h of ED arrival, the median D2F time was 90 min (IQR: 36 to 186 min), and 481 patients (37.3%) were categorized as the early treatment group. These patients were more likely to arrive by ambulance and had more signs of congestion compared with the nonearly treatment group. In-hospital mortality was significantly lower in the early treatment group (2.3% vs. 6.0% in the nonearly treatment group; p = 0.002). In multivariate analysis, earlier treatment remained significantly associated with lower in-hospital mortality (odds ratio: 0.39; 95% confidence interval: 0.20 to 0.76; p = 0.006).Conclusions: In this prospective multicenter, observational cohort study of patients presenting at the ED for AHF, early treatment with intravenous loop diuretics was associated with lower in-hospital mortality. (Registry focused on very early presentation and treatment in emergency department of acute heart failure syndrome; UMIN000014105). [ABSTRACT FROM AUTHOR]

Abstract: Serum neopterin concentration was measured in 198 patients with chronic heart failure (CHF) and 62 control subjects by ELISA. Patients were prospectively followed during a median follow-up period of 745days with end points of cardiac death or re-hospitalization due to progressive heart failure. Serum concentration of neopterin increased with advancing New York Heart Association (NYHA) functional class (P <0.001). High neopterin group had a significantly higher incidence of cardiac events than low neopterin group (P <0.0001). In the multivariate Cox analysis, serum neopterin concentration was an independent risk factor for cardiac events (hazard ratio 1.70, 95%CI 1.16–2.50, P =0.0068). Serum neopterin concentration is a novel prognostic marker for CHF. [ABSTRACT FROM AUTHOR]

Clinicopathological significances of heparanase activity in non-small cell lung cancer (NSCLC) were investigated by analyzing 76 resected specimens of NSCLC. Heparanase activities in NSCLC were significantly higher than non-cancerous lung tissues (P<0.0001). The heparanase activities of NSCLC were significantly higher in larger diameter tumors (P=0.0141) or with metastasis to ipsilateral mediastinal lymph nodes (P=0.0004). The activities of heparanase in primary tumors were increased significantly according to the pathological stage of the progression of the disease (P=0.0009). Among the clinicopathological parameters, histological cell type and evidence of ipsilateral lymph node metastasis showed a significant association with elevated heparanase activities, whereas age, degree of differentiation and tumor diameter did not. Kaplan–Meier curves for overall and disease-free survival demonstrated a significant difference between patients with elevated and non-elevated heparanase activity by log–rank test (P=0.0145 and 0.0002, respectively). Multivariate analysis showed heparanase activity was an independent factor to influence disease-free survival in our study. These results suggest that heparanase activity could be used as a prognostic indicator for postoperative patients with NSCLC and heparanase might be a promising molecular target for treatment of NSCLC. [Copyright &y& Elsevier]