Useful Prognostic Information In Patients Research Articles

#3437 THE ASSOCIATION OF INTERLEUKIN-6 TO ALBUMIN RATIO WITH MORTALITY IN PATIENTS WITH KIDNEY FAILURE

Abstract Background and Aims Systemic inflammation - characterized by high interleukin-6 (IL-6) and low albumin circulating concentrations - associates with worse outcomes in patients with kidney failure (KF). We examined the value of IL-6 to albumin ratio (IAR) to stratify risk of death in KF patients. Method In 435 incident dialysis patients (median age 56 years, 61.8% male, 31% diabetes mellitus (DM), 38.4% cardiovascular (CV) disease (CVD)), plasma IL-6 and albumin were measured at baseline to calculate IAR. We performed receiver operating characteristic curve (ROC) to compare the discriminatory performance of albumin, IL-6 and IAR for predicting all-cause and CV mortality. We divided patients into IAR tertiles and analysed: 1) cumulative incidence of all-cause mortality and CV mortality censored for renal transplantation during follow up of up to 60 months; 2) the association of IAR and all-cause and CV mortality risk according to Fine-Gray analysis taking renal transplantation as competing risk; and 3) the restricted mean survival time (RMST) and differences of RMST (∆RMST) between IAR tertiles to describe quantitative differences of survival time. Results Among 435 patients, 146 patients (33.6%) died, and 175 (40.2%) patients underwent renal transplantation during median 24.9 months of follow-up; 83 (56.8%) of the 146 deaths were due to CVD. The area under the ROC curve (AUC) of IAR (0.696 for all-cause mortality; 0.657 for CV mortality) was higher than that of both albumin and IL-6. As shown in Fig. 1 A and B: 1) the cumulative incidence of all-cause and CV mortality of patients in middle and high IAR tertiles was significantly higher than in low IAR tertile; 2) higher IAR associated with higher risk of all-cause (sub-hazard ratio (sHR) 1.93, 95% confidence interval (CI) 1.22-3.06 for high IAR tertile) and CV mortality (sHR 1.99, 95% CI 1.03-3.87 for middle IAR tertile) risk after adjusting for age, sex, DM, CVD, and smoking; and 3) ∆RMST at 59 months showed shorter survival time in middle and high IAR tertiles compared with low IAR tertile for all-cause (∆RMST -6.21 months for middle vs low tertile; ∆RMST -11.4 months for high vs low tertile) and CV mortality (∆RMST -4.73 months for middle vs low tertile; ∆RMST -7.49 months for high vs low tertile). Conclusion Higher IAR was independently associated with significantly higher all-cause and CV mortality risk in KF patients. These results suggest that IAR may provide useful prognostic information in patients with KF.

Interleukin-6-to-Albumin Ratio as a Superior Predictor of Mortality in End-Stage Kidney Disease Patients

Introduction: In patients with chronic kidney disease (CKD), high interleukin-6 (IL-6) and low albumin circulating concentrations are associated with worse outcomes. We examined the IL-6-to-albumin ratio (IAR) as a predictor of risk of death in incident dialysis patients. Methods: In 428 incident dialysis patients (median age 56 years, 62% men, 31% diabetes mellitus, 38% cardiovascular disease [CVD]), plasma IL-6 and albumin were measured at baseline to calculate IAR. We compared the discrimination of IAR with other risk factors for predicting 60-month mortality using receiver operating characteristic curve (ROC) and analyzed the association of IAR with mortality using Cox regression analysis. We divided patients into IAR tertiles and analyzed: (1) cumulative incidence of mortality and the association of IAR with mortality risk in Fine-Gray analysis, taking kidney transplantation as competing risk and (2) the restricted mean survival time (RMST) to 60-month mortality and differences of RMST (∆RMST) between IAR tertiles to describe quantitative differences of survival time. Results: For all-cause mortality, the area under the ROC curve (AUC) for IAR was 0.700, which was greater than for IL-6 and albumin separately, while for CV mortality, the AUC for IAR (0.658) showed negligible improvement over IL-6 and albumin separately. In Cox regression analysis, IAR was significantly associated with all-cause mortality but not with CV mortality. Both high versus low and middle versus low tertiles of IAR associated with higher risk of all-cause mortality, subdistribution hazard ratio of 2.22 (95% CI 1.40–3.52) and 1.85 (95% CI 1.16–2.95), respectively, after adjusting for age, sex, diabetes mellitus, CVD, smoking, and estimated glomerular filtration rate. ∆RMST at 60 months showed significantly shorter survival time in middle and high IAR tertiles compared with low IAR tertile for all-cause mortality. Conclusions: Higher IAR was independently associated with significantly higher all-cause mortality risk in incident dialysis patients. These results suggest that IAR may provide useful prognostic information in patients with CKD.

Ultrasound Renal Score to Predict the Renal Disease Prognosis in Patients with Diabetic Kidney Disease: An Investigative Study.

Renal disease associated with type 2 diabetes mellitus (T2DM) has become the leading cause of chronic kidney disease (CKD). Renal ultrasonography is an imaging examination required in the work-up of renal disease. This study aimed to identify the differences in renal ultrasonographic findings between patients with and without DM, and to evaluate the relationship between renal ultrasound findings and renal prognosis in patients with DM. A total of 252 patients who underwent renal ultrasonography at Chungnam National University Hospital were included. Kidney disease progression was defined as a ≥10% decline in the annual estimated glomerular filtration rate (eGFR), which, in this paper, is referred to as ΔeGFR/year, or the initiation of renal replacement therapy after follow-up. The renal scoring system was evaluated by summing up the following items: the value of renal parenchymal echogenicity (0: normal; 1: mildly increased; and 2: increased) and the shape of the cortical margin (0: normal and 1: irregular; right kidney length/height (RH-0 or 1), mean cortical thickness/renal length/height (CKH-0 or 1), and cortical thickness/parenchymal thickness (CK/PK-0 or 1) based on the median: 0-above median, and 1-below median). Patients with DM had thicker renal PKH than those without, despite having lower eGFRs (0.91 ± 0.15, 0.86 ± 0.14, p = 0.006). In the progression group, the renal scores were significantly higher than those from the non-progression group. In the multivariate logistic regression analysis, the higher renal scores, presence of DM, and younger age were independently predicted for renal disease progression after adjusting for confounding variables, such as the presence of hypertension, serum hemoglobin and albumin levels, and UPCR. In conclusion, patients with high renal scores were significantly associated with renal disease progression. Our results suggest that renal ultrasonography at the time of diagnosis provides useful prognostic information in patients with kidney disease.

The clinical relevance of quality of life in patients with acute decompensated heart failure with preserved ejection fraction: insights from the PURSUIT-HFpEF Registry

Abstract Background Improvement of quality of life (QOL) is one of the most important therapeutic goals for patients with heart failure with preserved ejection fraction (HFpEF). It is, therefore, clinically relevant to comprehensively identify aggravating factors among cardiac factors, non-cardiac comorbidities, and social factors. The aim of this study was to elucidate determinant factors of impaired QOL and clarify the association between QOL and prognosis in patients with HFpEF. Methods and results Patient data were extracted from The Prospective mUlticenteR obServational stUdy of patIenTs with Heart Failure with Preserved Ejection Fraction (PURSUIT HFpEF) study. EuroQol 5 dimensions 5-level (EQ-5D-5L) data were obtained at discharge to evaluate patients' health-related QOL. A total of 864 patients were enrolled in this study. Multivariable logistic regression analysis revealed that only non-cardiac factors such as age, female sex, frailty, malnutrition and inflammation were significantly associated with low EQ-5D-5L score, whereas cardiac factors showed no significant association after multivariable adjustment. A total of 206 patients died over a mean follow-up period of 2.0±1.2 years. Kaplan–Meier survival curve analysis demonstrated a significant increase in risk of mortality stratified by tertiles of EQ-5D-5L score (p<0.0001). Cox multivariable analysis revealed that patients with low EQ-5D-5L score had a significantly greater risk of mortality than those with high EQ-5D-5L score (adjusted hazard ratio: 2.20 (1.40–3.45), p=0.001). Conclusion Among patients with HFpEF, non-cardiac factors such as age, female sex, frailty, malnutrition and inflammation are significantly associated with impaired QOL. The QOL score itself also offers useful prognostic information in patients with HFpEF. Funding Acknowledgement Type of funding sources: None.

ATP7B Genotype and Chronic Liver Disease Treatment Outcomes in Wilson Disease: Worse Survival With Loss-of-Function Variants

Background and AimsAlthough a good genotype-phenotype correlation has not been established in Wilson disease (WD), patients with loss-of-function (LOF) ATP7B variants demonstrate different clinical and biochemical characteristics. We aim to describe long-term treatment outcomes in the chronic liver disease (CLD) phenotype and evaluate an association with LOF variants. MethodsThis was a single-center retrospective review of WD patients with at least 1 variant in ATP7B. Demographic, biochemical, genetic, and clinical parameters were obtained. The composite clinical endpoint of liver transplantation or death was used for probands with CLD phenotype on chelators. ResultsOf 117 patients with hepatic WD: 71 had CLD, 27 had fulminant hepatic failure requiring urgent liver transplantation, and 19 were diagnosed through family screening. Median age at diagnosis was 13.1 (interquartile range, 9.7–17.6) years. In total, 91 variants in ATP7B were identified in the study population. At least 1 LOF variant was present in 60 (51.3%) patients. During median follow-up of 10.7 (interquartile range, 6.7–18.9) years, 10 (14.1%) of the probands with CLD reached the composite endpoint. There was a worse transplant-free survival for patients prescribed chelation therapy in patients with at least 1 LOF variant (P = .03). ConclusionsPatients with WD and CLD phenotype on chelators, who have at least 1 LOF variant in ATP7B, have a worse prognosis during long-term follow up. This subgroup of patients requires close monitoring for signs of progressive liver disease. Sequencing of ATP7B may be used in the diagnosis of WD, and in addition, it may provide useful prognostic information for patients with hepatic WD.

A Need for More Molecular Profiling in Brain Metastases.

As local disease control improves, the public health impact of brain metastases (BrM) continues to grow. Molecular features are frequently different between primary and metastatic tumors as a result of clonal evolution during neoplasm migration, selective pressures imposed by systemic treatments, and differences in the local microenvironment. However, biomarker information in BrM is not routinely obtained despite emerging evidence of its clinical value. We review evidence of discordance in clinically actionable biomarkers between primary tumors, extracranial metastases, and BrM. Although BrM biopsy/resection imposes clinical risks, these risks must be weighed against the potential benefits of assessing biomarkers in BrM. First, new treatment targets unique to a patient’s BrM may be identified. Second, as BrM may occur late in a patient’s disease course, resistance to initial targeted therapies and/or loss of previously identified biomarkers can occur by the time of occult BrM, rendering initial and other targeted therapies ineffective. Thus, current biomarker data can inform real-time treatment options. Third, biomarker information in BrM may provide useful prognostic information for patients. Appreciating the importance of biomarker analyses in BrM tissue, including how it may identify specific drivers of BrM, is critical for the development of more effective treatment strategies to improve outcomes for this growing patient population.

Roles of Morris Index on Poor Outcomes in Patients with Non-ST Segment Elevation Acute Coronary Syndrome

BackgroundThis study aimed to assess the roles of the Morris index in predicting poor outcomes in patients with non-ST segment elevation acute coronary syndrome (NSTE-ACS).Material/MethodsThis study included 905 patients with newly diagnosed NSTE-ACS. The Morris index, also known as P wave terminal force in lead V1 (PTFV1), was recorded at admission and discharge. PTVF1 (+) was defined as an absolute value >0.04 mm·s, while PTFV1 (−) was defined as an absolute value <0.04 mm·s. Based on their PTFV1 values at admission/discharge, patients were divided into 4 groups: PTFV1 (−)/(−), PTFV1 (+)/(−), PTFV1 (−)/(+), and PTFV1 (+)/(+). Univariate and multivariate regression analyses were utilized to identify the variables that could contribute to NSTE-ACS risk.ResultsCompared with the PTFV1 (−)/(−) group, the incidence of poor outcomes was significantly higher in the PTFV1 (−)/(+) (hazard ratio [HR], 3.548; 95% confidence interval [95% CI], 2.024–6.219) and PTFV1 (+)/(+) (HR, 2.133; 95% CI, 1.141–3.986) groups, but not statistically different in the PTFV1 (+)/(−) group (risk ratio, 0.983; 95% CI, 0.424–2.277).ConclusionsPrimary PTFV1 (+) at discharge and PTFV1 (+) during hospitalization were independent risk factors for poor outcomes, which may provide useful prognostic information for patients with NSTE-ACS.

Association of plasma level of growth differentiation factor-15 and clinical outcome after intraarterial thrombectomy

Background and purposeAs intraarterial thrombectomy (IAT) has been actively practiced, blood biomarkers that can predict outcomes after IAT have drawn attention. Growth differentiation factor-15 (GDF-15) is a stress-responsive cytokine and the levels are increased during inflammation or other pathological conditions of various tissues, including the brain. However, GDF-15 levels have not been reported as a biomarker for IAT outcomes. This study was performed to evaluate whether GDF-15 was related to the extent of brain damage and whether it could predict patient prognosis after IAT. MethodsPatients who showed large arterial occlusion and significant diffusion-perfusion mismatch on imaging underwent IAT. A total of 62 patients who underwent IAT and had blood samples for GDF-15 measurements were enrolled from July 2013 to May 2015. We assessed the infarct severity by consecutive changes on the National Institutes of Health Stroke Scale (NIHSS) during admission and the size of the infarction on brain imaging. Modified Rankin Scale scores (mRS) from 0 to 2 were considered good outcomes, representing functional independence at discharge and three months later. ResultsThe levels of GDF-15 at the time of admission were significantly correlated with the NIHSS scored at 24 hours (r = 0.306, p = 0.016), three days after IAT (r = 0.261, p = 0.041), and at discharge (r = 0.266, p = 0.037), as well as the infarct size on diffusion-weighted image taken 24 h after IAT (r = 0.452, p = 0.001), but the levels were not correlated with the initial NIHSS or the infarct size before IAT. Multiple logistic regression showed that GDF-15 levels were an independent predictor of functional independence (mRS 0 – 2) at discharge (p = 0.028) and three months after IAT (p = 0.019). Other factors that could predict prognosis were good collateral status on the initial brain angiography and rapid recanalization within six hours from symptom onset. ConclusionThe GDF-15 level at the time of admission showed a significant positive correlation with the severity of cerebral damage and clinical outcome after IAT. This suggests that GDF-15 can provide useful prognostic information for patients who successfully underwent IAT in an emergency setting.

Evaluation of pulse pressure and proportional pulse pressure as predictors of severity among patients having heart failure with reduced ejection fraction.

Introduction:Proportional Pulse Pressure (PPP) is a significant risk indicator in heart failure. PPP is a simple, inexpensive and easily measurable clinical index. This non-invasive test provides useful prognostic information for patients with heart failure with reduced ejection fraction (EF) particularly in those with an EF < 30% where lower proportional pulse pressure independently predicts mortality.Methods:A prospective observational study involving 150 patients with reduced ejection fraction was done. Detailed history, clinical examination and parameters like pulse pressure, proportional pulse pressure were evaluated and correlated with ejection fraction.Results:The mean age of the patients was 58.99 ± 11.03 years and the majority of the study participants (57.33 %) were between 45 and 65 years of age. The most common etiology of heart failure (HF) was coronary heart disease in this study (76%). Proportional Pulse pressure showed significant association with ejection fraction. The specificity for detecting heart failure was more for proportional pulse pressure and systolic blood pressure (95 % each).Conclusion:Proportional Pulse Pressure may help to identify HF patients who present with low cardiac output, low ejection fraction, and worse prognosis. Our current observations reinforce the importance of clinically based skills that must not be forgotten when managing HF.

SUN-022 SERUM GDF15 AS A PROGNOSTIC MARKER OF MEMBRANOUS GLOMERULONEPHRITIS

Idiopathic membranous nephropathy (IMN) is a major cause of nephrotic syndrome. Growth differentiation factor-15 (GDF-15) is a member of the transforming growth factor-β superfamily and has been associated with chronic inflammatory disease. It has the potential to be a useful prognostic marker in patients with renal diseases, such as diabetic nephropathy and IgA nephropathy. This study examined whether GDF-15 is associated with the clinical parameters in IMN and showed that GDF-15 can predict IMN disease progression. A total of 35 patients with biopsy-proven IMN, treated at Chungnam National University Hospital from January 2010 to December 2015, were included. Patients younger than 18 years, those with secondary membranous nephropathy, and those lost to follow-up before 12 months were excluded. Levels of GDF-15 at the time of biopsy were measured using enzymelinked immunosorbent assays. Disease progression was defined as a ≥30% decline in estimated glomerular filtration rate (eGFR) or the development of end-stage renal disease. The mean follow-up was 44.1 months (range: 16–72 months). Using receiver operating curve analysis, the best serum GDF-15 cut-off value for predicting disease progression was 2.15 ng/ml (sensitivity: 75.0%, specificity: 82.1%, p = 0 007). GDF-15 was significantly related to age and initial renal function. In the Kaplan-Meier analysis, the risk of disease progression increased in patients with GDF-15 ≥ 2.15 ng/ml when compared with those with GDF-15 < 2.15 ng/ml (50.0% versus 9.7%) (p = 0 012). In the multivariate Cox regression analysis adjusted for potential confounders, only GDF-15 was significantly associated with disease progression in IMN (p = 0 032). The GDF-15 level at the time of diagnosis has a significant negative correlation with initial renal function and is associated with a poor prognosis in IMN. Our results suggest that GDF-15 provides useful prognostic information in patients with IMN.

Low lymphocyte monocyte ratio after neoadjuvant therapy predicts poor survival after pancreatectomy in patients with borderline resectable pancreatic cancer

BackgroundThe impact of systemic immune inflammatory markers to predict survival in patients receiving neoadjuvant therapy for borderline resectable pancreatic cancer has not been sufficiently investigated. This study aims to evaluate whether systemic immune inflammatory markers after neoadjuvant therapy followed by pancreatectomy become preoperative prognostic factors to predict survival in patients with borderline resectable pancreatic cancer. MethodsWe retrospectively reviewed 67 borderline resectable pancreatic cancer patients receiving neoadjuvant therapy and 58 borderline resectable pancreatic cancer patients undergoing upfront surgery between 2010 and 2016. The association between survival and systemic immune inflammatory markers was evaluated by univariate and multivariate analysis. The neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, lymphocyte-to-monocyte ratio, and prognostic nutrition index were assessed as systemic immune inflammatory markers. ResultsIn univariate analysis, the postneoadjuvant neutrophil-to-lymphocyte ratio, lymphocyte-to-monocyte ratio, and prognostic nutrition index are significantly associated with survival as systemic immune inflammatory markers. The optimal cutoff value of the postneoadjuvant neutrophil-to-lymphocyte ratio, lymphocyte-to-monocyte ratio, and prognostic nutrition index were 2.5, 3.0, and 45, respectively. Patients with a lymphocyte-to-monocyte ratio <3.0 had significantly poor survival compared with those who had a lymphocyte-to-monocyte ratio ≥3.0 (14.9 months vs 31.7 months, P = .006). The multivariate analysis identified the following as predictors of poor prognosis: postneoadjuvant lymphocyte-to-monocyte ratio <3.0 (HR 2.59; 95% CI 1.02–6.58; P = .045), T4 (HR 1.82; 95% CI 1.11–3.01; P = .029), lymph node status (HR 2.62; 95% CI 1.24–5.51; P = .012), and no completion of adjuvant therapy (HR 7.09; 95% CI 3.08–16.4; P < .001). ConclusionA low lymphocyte-to-monocyte ratio after neoadjuvant therapy is useful prognostic information for patients with borderline resectable pancreatic cancer. This result might indicate a potential role of lymphocyte-to-monocyte ratios in stratification of treatment strategy in borderline resectable pancreatic cancer patients.

Prognostic Impact of Nutritional Status Assessed by the Controlling Nutritional Status (CONUT) Score in Patients with Surgically Treated Renal Cell Carcinoma

Purpose: The prognostic role of the controlling nutritional status (CONUT) score in renal cell carcinoma (RCC) has not been evaluated. The aim of the current study was to clarify the prognostic significance of the CONUT score in Korean patients with surgically treated RCC.Materials and methods: A database of 1,881 patients with surgically treated RCC from a multiinstitutional Korean collaboration between 1999 and 2015 was analyzed. The preoperative CONUT score was calculated from serum albumin, total cholesterol concentrations, and total lymphocyte count. Clinicopathological variables and survival rates were compared between the CONUT score groups.Results: A high CONUT score was associated with older age, lower body mass index, lower preoperative prognostic nutritional index, and presence of diabetes or hypertension (each P < 0.001). Regarding pathologic features, a high CONUT score was associated with aggressive tumor characteristics including large tumor size, advanced stage, high nuclear grade, lymphovascular invasion, and sarcomatous differentiation (each P < 0.001). Multivariate Cox regression analysis indicated that a high CONUT score (≥ 2) was an independent predictor of cancer-specific mortality (hazard ratio, 1.892; 95% CI: 1.118–3.201; P = 0.018).Conclusion: The CONUT score, an easily measurable immune-nutritional biomarker, may provide useful prognostic information in patients with surgically treated RCC.

Growth Differentiation Factor-15 as a Predictor of Idiopathic Membranous Nephropathy Progression: A Retrospective Study.

Idiopathic membranous nephropathy (IMN) is a major cause of nephrotic syndrome. No biomarker to predict the long-term prognosis of IMN is currently available. Growth differentiation factor-15 (GDF-15) is a member of the transforming growth factor-β superfamily and has been associated with chronic inflammatory disease. It has the potential to be a useful prognostic marker in patients with renal diseases, such as diabetic nephropathy and IgA nephropathy. This study examined whether GDF-15 is associated with the clinical parameters in IMN and showed that GDF-15 can predict IMN disease progression. A total of 35 patients with biopsy-proven IMN, treated at Chungnam National University Hospital from January 2010 to December 2015, were included. Patients younger than 18 years, those with secondary membranous nephropathy, and those lost to follow-up before 12 months were excluded. Levels of GDF-15 at the time of biopsy were measured using enzyme-linked immunosorbent assays. Disease progression was defined as a ≥30% decline in estimated glomerular filtration rate (eGFR) or the development of end-stage renal disease. The mean follow-up was 44.1 months (range: 16–72 months). Using receiver operating curve analysis, the best serum GDF-15 cut-off value for predicting disease progression was 2.15 ng/ml (sensitivity: 75.0%, specificity: 82.1%, p = 0.007). GDF-15 was significantly related to age and initial renal function. In the Kaplan-Meier analysis, the risk of disease progression increased in patients with GDF-15 ≥ 2.15 ng/ml when compared with those with GDF-15 < 2.15 ng/ml (50.0% versus 9.7%) (p = 0.012). In the multivariate Cox regression analysis adjusted for potential confounders, only GDF-15 was significantly associated with disease progression in IMN (p = 0.032). In conclusion, the GDF-15 level at the time of diagnosis has a significant negative correlation with initial renal function and is associated with a poor prognosis in IMN. Our results suggest that GDF-15 provides useful prognostic information in patients with IMN.

Role of positron emission tomography in thyroid and neuroendocrine tumors.

Positron emission tomography (PET) is an established imaging method in oncology. PET/computed tomography (PET/CT) and PET/magnetic resonance imaging (PET/MRI) are hybrid techniques which combine morphological information obtained by CT and MRI with functional data provided by PET. Several PET radiotracers evaluating different metabolic pathways or receptor status can be used to assess endocrine tumors such as thyroid tumors or neuroendocrine neoplasms (NENs). This review is focused to describe the role of PET imaging using different radiotracers in patients with thyroid tumors and NENs. The role of PET imaging with different radiotracers in several endocrine tumors including thyroid tumors, gastroenteropancreatic neoplasms, lung neuroendocrine neoplasms, pheochromocytomas and paragangliomas, and multiple endocrine neoplasia syndromes has been described. Fluorine-18 fluorodeoxyglucose (18F-FDG) PET evaluating the glucose metabolism provides useful diagnostic and prognostic information in patients with thyroid tumors. Iodine-124 (124I) assessing the iodine metabolism may be used for dosimetry and diagnostic purposes in thyroid tumors. In patients with NENs specific radiotracers can be used for diagnostic purposes such as somatostatin analogues labeled with gallium-68 (68Ga-DOTA-peptides) evaluating somatostatin receptor expression and fluorine-18 fluorodihydroxyphenylalanine (18F-FDOPA) assessing the uptake, decarboxylation and storage of amine precursors. One advantage of 68Ga-DOTA-peptides PET is to select patients with well-differentiated and inoperable NENs for peptide receptor radionuclide therapy. 18F-FDG PET may provide useful prognostic information in patients with high-grade NENs. PET imaging with different radiotracers is a useful functional imaging technique in the work-up of several endocrine tumors.

Development and validation of multivariable models to predict mortality and hospitalization in patients with heart failure.

From a prospective multicentre multicountry clinical trial, we developed and validated risk models to predict prospective all-cause mortality and hospitalizations because of heart failure (HF) in patients with HF. BIOSTAT-CHF is a research programme designed to develop and externally validate risk models to predict all-cause mortality and HF hospitalizations. The index cohort consisted of 2516 patients with HF from 69 centres in 11 European countries. The external validation cohort consisted of 1738 comparable patients from six centres in Scotland, UK. Patients from the index cohort had a mean age of 69 years, 27% were female, 83% were in New York Heart Association (NYHA) class II-III and the mean left ventricular ejection fraction (LVEF) was 31%. The full prediction models for mortality, hospitalization owing to HF, and the combined outcome, yielded c-statistic values of 0.73, 0.69, and 0.71, respectively. Predictors of mortality and hospitalization owing to HF were remarkably different. The five strongest predictors of mortality were more advanced age, higher blood urea nitrogen and N-terminal pro-B-type natriuretic peptide, lower haemoglobin, and failure to prescribe a beta-blocker. The five strongest predictors of hospitalization owing to HF were more advanced age, previous hospitalization owing to HF, presence of oedema, lower systolic blood pressure and lower estimated glomerular filtration rate. Patients from the validation cohort were aged 74 years, 34% were female, 85% were in NYHA class II-III, and mean LVEF was 41%; c-statistic values for the full and compact model were comparable to the index cohort. A small number of variables, which are usually readily available in the routine clinical setting, provide useful prognostic information for patients with HF. Predictors of mortality were remarkably different from predictors of hospitalization owing to HF.

Prognostic Impact of Placental Growth Factor on Mortality and Cardiovascular Events in Dialysis Patients

Background: Placental growth factor (PlGF), a member of the vascular endothelial growth factor (VEGF) family, has recently emerged as a predictor of survival and cardiovascular risk. Along with others, we have shown an independent association between PlGF and cardiovascular events in CKD patients, but not much is known about patients receiving dialysis. Methods: We studied 205 dialysis patients undergoing cardiac catheterization at the Nara Medical University between April 1, 2004, and December 31, 2012. Serum levels of PlGF and VEGF were measured with ELISA in all the patients. Results: During a median follow-up of 20 months, 121 participants died from any cause or experienced a cardiovascular event. In the fully adjusted analysis, having an above-median PlGF or VEGF level was associated with a hazards ratio for adverse outcomes of 2.55 (1.72-3.83) and 1.39 (0.95-2.04), respectively. Using a multimarker strategy in a model with age, serum albumin, history of coronary artery disease, brain natriuretic peptide and PlGF, patients with 2, 3 and 4 positive markers had a 3.82-, 5.77- and 6.59-fold higher risk of mortality or a cardiovascular event, respectively, compared to those with no positive markers. The model with PlGF had a significantly higher c-statistic, integrated discrimination improvement index and category-free net reclassification improvement index than the model without PlGF. Conclusion: PlGF is independently associated with mortality and cardiovascular events, but the association between VEGF and adverse events was attenuated with covariate adjustment. The addition of PlGF to models with established clinical predictors provides additional useful prognostic information in patients receiving dialysis.

ST Elevation in Lead aVR and In-Hospital and Mid-Term Adverse Events in Patients with Medically Treated ST Elevation Myocardial Infarction

Background: ST segment elevation and deviation in lead aVR can provide useful prognostic information in patients with ST elevation myocardial infarction (STEMI). The aim of the present study was evaluation of the effect of aVR ST elevation (aVR-STE) and aVR ST deviation (aVR-STD) the in-hospital and sixmonth prognosis of patients with STEMI. Methods: The study was a cohort of medically treated patients with acute STEMI. The patients were categorized as aVR ST elevation (aVR-STE) or aVR ST deviation (aVR-STD) if there was > 0.05 mv ST elevation or ST deviation in lead aVR, respectively; otherwise, they were categorized as control groups. Results: 334 patients [49 patients (14.67%) with aVR-STE and 159 patients (47.60%) with aVR-STD] were included. The mean age of the study group was 59.62 ± 13.03 years and 75.4% were male. In-hospital mortality was not significantly different in patients with or without aVR-STE or aVR-STD. Pulmonary edema or overt decompensated heart failure was seen more in patients with aVRSTE [Relative risk (RR): 3.393, 95% confidence interval: 1.405-8.192, P = 0.012] and it trended more in patients with aVR-STD (P = 0.06). 6-month follow up: Mortality was not significantly different among patients with or without aVR-STE or aVR-STD. Pulmonary edema or overt decompensated heart failure occurred more in patients with aVR-STE and aVR-STD (RR: 3.190, 95% confidence interval: 1.684-6.046, P < 0.0001, RR: 1.937, 95% confidence interval: 0.987-3.800, P = 0.049).

Comparison of different types of cardiac amyloidosis by cardiac magnetic resonance imaging

Objectives: We sought to determine cardiac morphological and functional differences between light-chain (AL), mutant-type transthyretin (ATTRmt) and wild-type TTR (ATTRwt) amyloidosis using contrast-enhancement cardiac magnetic resonance imaging (CE-CMR). Finally, we attempted to establish the diagnostic and prognostic impact of these findings. Introduction: The most common forms of cardiac amyloid are AL and ATTR amyloidosis, but the clinical courses of these variants are quite heterogeneous. While CE-CMR is used to evaluate patients with cardiac amyloidosis, its ability to predict prognosis in these patients is debatable.Methods: About 130 patients with cardiac amyloidosis (AL, n = 62; ATTRmt, n = 30, ATTRwt, n = 33) were assessed by CE-CMR (cardiac morphology, cardiac function, late gadolinium enhancement).Results: Left ventricular (LV) mass, basal and mid-ventricular maximal wall thickness, and thickness of the inter-atrial septum were higher in ATTRwt when compared to AL and ATTRmt amyloidosis. Tricuspid annular excursion was lower in ATTRwt amyloidosis than in AL amyloidosis. CE was observed in 94.6% of the patients (AL 80.6%; ATTRmt 90%; ATTRwt 87.9%) with significant differences in quality and intensity between the groups. Differentiation of amyloid types was achieved by combination of age, number of organs, the presence of inferolateral CE-CMR, thickness of inter-atrial septum and troponin T. Overall 1-year-survival rates were 93.3, 93.9 and 70.5% in ATTRwt, ATTRmt and AL amyloidosis, respectively. LV mass, mitral annular excursion and NT-proBNP in AL amyloidosis, LV mass maximal apical wall thickness and troponin T in ATTRwt amyloidosis, and finally NT-proBNP and renal function in ATTRmt amyloidosis were independent predictors of outcome.Conclusions: This study demonstrates that CE-CMR can highlight morphological and functional differences between different types of cardiac amyloidosis. In addition, CE-CMR and cardiac biomarkers provide useful prognostic information in patients with cardiac amyloidosis.

Assessment of transthyretin combined with mini nutritional assessment on admission provides useful prognostic information in patients with acute decompensated heart failure.

Decreased Transthyretin (TTR) can be observed in heart failure patients with malnutrition evaluated by the Mini Nutritional Assessment (MNA). This study investigated whether a combination of different nutritional assessment methods would be useful for assessing prognosis in patients with acute decompensated heart failure (ADHF).This prospective study included 52 patients with ADHF (mean age, 71.1 ± 14.7 years; men 55.8%) who were admitted to our hospital between June 2012 and August 2013. On admission, nutritional status was evaluated according to levels of TTR and the MNA. Of 52 patients, 28 (53.8%) had TTR < 15 mg/dL, 39 (75.0%) had malnutrition or were at risk of malnutrition (MNA score ≤ 23.5), and 21 (40.4%) were categorized into group L (MNA score ≤ 23.5 and TTR < 15 mg/dL). Readmission due to worsening heart failure occurred in 12 patients (23.1%), and there were 4 (7.7%) allcause deaths. The 1-year event-free survival rates in group L and the remaining patients (group O) were 27.7% and 85.6%, respectively (P = 0.001). Using Cox multivariate analysis, group L also had a poorer prognosis (hazard ratio 4.35, 95% confidence interval 1.26-17.74, P = 0.020).MNA revealed that 75% of patients with ADHF had malnutrition or were at risk of malnutrition. The combination of low MNA and low TTR on admission can predict the prognosis of patients with ADHF.

Ki-67 proliferation index and clinicopathological patterns in colorectal carcinomas

Background: Tumour, node, metastasis (TNM) staging system provides useful prognostic information in patients with colorectal carcinoma (CRC). An improved prognostication and patient survival may be achieved by employing immunohistochemistry studies with proliferation markers like Ki-67. Material and methods: We prospectively studied 51 patients with CRC and evaluated the clinicopathological patterns of CRC and the relationship of with the clinicopathological variables Results: Their mean age was 48 (range 17-75) years; majority (64.7%) were males. Rectum was the most common subsite affected (45.1%). Histopathologically most of the tumours (86.3%) were usual type adenocarcinomas and were of grade 1 morphology (51%). The Ki-67 proliferation index (PI) ranged from 8.4% to 84.4%. The mean PI was greater in patients aged less than or equal to 50 years than in those aged above 50 years, in males than females, in rectal cancers than colonic cancers. It was greater in mucinous carcinomas than usual type adenocarcinomas, in grade 3 tumours than lower grade tumours (grades 1 and 2) and in T4 than T3 and T2 tumours. There was a significant positive correlation between the PI values and grade of the tumour. Conclusion: We concluded that Ki-67 proliferation marker may be useful as an additional tool to assess the tumour aggressiveness with respect to certain clinicopathological parameters in colorectal carcinomas.