Hyponatremia and Congestive Heart Failure: A Marker of Increased Mortality and a Target for Therapy

Heart failure is one of the most common chronic medical conditions in the developed world. It is characterized by neurohormonal activation of multiple systems that can lead to clinical deterioration and significant morbidity and mortality. In this regard, hyponatremia is due to inappropriate and continued vasopressin activity despite hypoosmolality and volume overload. Hyponatremia is also due to diuretic use in an attempt to manage volume overload. When hyponatremia occurs, it is a marker of heart failure severity and identifies patients with increased mortality. The recent introduction of specific vasopressin-receptor antagonists offers a targeted pharmacological approach to these pathophysiological derangements. Thus far, clinical trials with vasopressin-receptor antagonists have demonstrated an increase in free-water excretion, improvement in serum sodium, modest improvements in dyspnea but no improvement in mortality. Continued clinical trials with these agents are needed to determine their specific role in the treatment of both chronic and decompensated heart failure

Clinical adjudication in acute kidney injury studies: findings from the pivotal TIMP-2*IGFBP7 biomarker study

Background The NEPROCHECK test (Astute Medical, San Diego, CA, USA) combines urinary tissue inhibitor of metalloproteinases-2 (TIMP-2) and insulin-like growth factor binding protein 7 (IGFBP7) to identify patients at high risk for acute kidney injury (AKI). In a US Food and Drug Administration registration trial (NCT01573962), AKI was determined by a three-member clinical adjudication committee. The objectives were to examine agreement among adjudicators as well as between adjudicators and consensus criteria for AKI and to determine the relationship of biomarker concentrations and adjudicator agreement. Methods Subjects were classified as AKI 3/3, 2/3, 1/3 or 0/3 according to the proportion of adjudicators classifying the case as AKI. Subjects were classified as Kidney Disease: Improving Global Outcomes (KDIGO) AKI(+) when stage 2 or 3 AKI criteria were met. Results Concordance between adjudicators and between adjudicators and KDIGO criteria were lower for AKI than non-AKI subjects [78.9 versus 97.3% (P \u3c 0.001) and 91.5 versus 97.9% (P = 0.01)]. Subjects who were AKI 3/3 or 2/3 but KDIGO AKI(−) had higher median [TIMP-2]•[IGFBP7] compared with those who were AKI-1/3 or 0/3 but KDIGO AKI(+) {2.78 [interquartile range (IQR) 2.33–3.56] versus 0.52 [IQR 0.26–1.64]; P = 0.008}. [TIMP-2]•[IGFBP7] levels were highest in patients with AKI 3/3 and lowest in AKI 0/3, whereas AKI 2/3 and 1/3 exhibited intermediate values. Conclusions In this analysis, urine [TIMP-2]•[IGFBP7] levels correlated to clinically adjudicated AKI better than to KDIGO criteria. Furthermore, in difficult cases where adjudicators overruled KDIGO criteria, the biomarker test discriminated well. This study highlights the importance of clinical adjudication of AKI for biomarker studies and lends further support for the value of urine [TIMP-2]•[IGFBP7]

Statement of the Third International Exercise-Associated Hyponatremia Consensus Development Conference, Carlsbad, California, 2015

The third International Exercise-Associated Hyponatremia (EAH) Consensus Development Conference convened in Carlsbad, California in February 2015 with a panel of 17 international experts. The delegates represented 4 countries and 9 medical and scientific sub-specialties pertaining to athletic training, exercise physiology, sports medicine, water/sodium metabolism, and body fluid homeostasis. The primary goal of the panel was to review the existing data on EAH and update the 2008 Consensus Statement.1 This document serves to replace the second International EAH Consensus Development Conference Statement and launch an educational campaign designed to address the morbidity and mortality associated with a preventable and treatable fluid imbalance. The following statement is a summary of the data synthesized by the 2015 EAH Consensus Panel and represents an evolution of the most current knowledge on EAH. This document will summarize the most current information on the prevalence, etiology, diagnosis, treatment and prevention of EAH for medical personnel, athletes, athletic trainers, and the greater public. The EAH Consensus Panel strove to clearly articulate what we agreed upon, did not agree upon, and did not know, including minority viewpoints that were supported by clinical experience and experimental data. Further updates will be necessary to both: (1) remain current with our understanding and (2) critically assess the effectiveness of our present recommendations. Suggestions for future research and educational strategies to reduce the incidence and prevalence of EAH are provided at the end of the document as well as areas of controversy that remain in this topic. [excerpt

Risk Prediction for Breast, Endometrial, and Ovarian Cancer in White Women Aged 50 y or Older: Derivation and Validation from Population-Based Cohort Studies

Background: Breast, endometrial, and ovarian cancers share some hormonal and epidemiologic risk factors. While several models predict absolute risk of breast cancer, there are few models for ovarian cancer in the general population, and none for endometrial cancer. Methods and Findings: Using data on white, non-Hispanic women aged 50+ y from two large population-based cohorts (the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial [PLCO] and the National Institutes of Health–AARP Diet and Health Study [NIH-AARP]), we estimated relative and attributable risks and combined them with age-specific US-population incidence and competing mortality rates. All models included parity. The breast cancer model additionally included estrogen and progestin menopausal hormone therapy (MHT) use, other MHT use, age at first live birth, menopausal status, age at menopause, family history of breast or ovarian cancer, benign breast disease/biopsies, alcohol consumption, and body mass index (BMI); the endometrial model included menopausal status, age at menopause, BMI, smoking, oral contraceptive use, MHT use, and an interaction term between BMI and MHT use; the ovarian model included oral contraceptive use, MHT use, and family history or breast or ovarian cancer. In independent validation data (Nurses' Health Study cohort) the breast and ovarian cancer models were well calibrated; expected to observed cancer ratios were 1.00 (95% confidence interval [CI]: 0.96–1.04) for breast cancer and 1.08 (95% CI: 0.97–1.19) for ovarian cancer. The number of endometrial cancers was significantly overestimated, expected/observed = 1.20 (95% CI: 1.11–1.29). The areas under the receiver operating characteristic curves (AUCs; discriminatory power) were 0.58 (95% CI: 0.57–0.59), 0.59 (95% CI: 0.56–0.63), and 0.68 (95% CI: 0.66–0.70) for the breast, ovarian, and endometrial models, respectively. Conclusions: These models predict absolute risks for breast, endometrial, and ovarian cancers from easily obtainable risk factors and may assist in clinical decision-making. Limitations are the modest discriminatory ability of the breast and ovarian models and that these models may not generalize to women of other races. Please see later in the article for the Editors' Summar

B-Type Natriuretic Peptide in the Critically Ill with Acute Kidney Injury

Introduction. Acute kidney injury (AKI) is common in the intensive care unit (ICU) and associated with poor outcome. Plasma B-type natriuretic peptide (BNP) is a biomarker related to myocardial overload, and is elevated in some ICU patients. There is a high prevalence of both cardiac and renal dysfunction in ICU patients. Aims. To investigate whether plasma BNP levels in the first 48 hours were associated with AKI in ICU patients. Methods. We studied a cohort of 34 consecutive ICU patients. Primary outcome was presence of AKI on presentation, or during ICU stay. Results. For patients with AKI on presentation, BNP was statistically higher at 24 and 48 hours than No-AKI patients (865 versus 148 pg/mL; 1380 versus 131 pg/mL). For patients developing AKI during 48 hours, BNP was statistically higher at 0, 24 and 48 hours than No-AKI patients (510 versus 197 pg/mL; 552 versus 124 pg/mL; 949 versus 104 pg/mL). Conclusion. Critically ill patients with AKI on presentation or during ICU stay have higher levels of the cardiac biomarker BNP relative to No-AKI patients. Elevated levels of plasma BNP may help identify patients with elevated risk of AKI in the ICU setting. The mechanism for this cardiorenal connection requires further investigation

The role of an electronic alert system to detect acute kidney injury in hospitalized patients: DETECT-H Project

Background and aims: Acute kidney injury (AKI) is associated with higher mortality and length of stay (LOS) for hospitalized patients. To improve outcomes, an electronic detection system could be a useful tool for early diagnosis. Methods: A fully automated real-time system for detecting decreased glomerular filtration rate in adult patients was developed in our hospital, DETECT-H project. AKI was established according to KDIGO guidelines. Results: In six months, 1241 alerts from 11,022 admissions were issued. Overall incidence of AKI was 7.7%. Highest AKI stage reached was: stage 1 (49.8%), 2 (24.5%) and 3 (25.8%), in-hospital mortality was 10.9%, 22.7%, 33.9% respectively and 57.1% in AKI requiring dialysis; mortality in stable CKD was 4.3%. Median LOS was 8 days versus 5 days for all patients. AKI was associated with a mortality of 3.18 (95% CI 1.80–5.59) and a LOS 1.52 (1.11–2.08) times as high as that for admissions without AKI. Multivariate analysis indicated that a LOS higher than 8 days was associated with AKI. Previous CKD was noted in 31.9% and AKI in 45.3% at discharge. As compared to the use of the detect system, only one third of CKD patients and half of AKI episodes were identified. Conclusions: CKD and in-hospital AKI are under-recognized entities. Mortality and LOS are increased in-hospital patients with renal dysfunction. AKI severity was associated with higher mortality and LOS. An automated electronic detection system for identifying renal dysfunction would be a useful tool to improve renal outcomes. Resumen: Introducción y objetivos: El fracaso renal agudo (FRA) aumenta la mortalidad y la estancia hospitalarias (EH). El empleo de sistemas de detección electrónica podría ser una herramienta beneficiosa para mejorar estos resultados. Métodos: Se desarrolló un sistema de detección automático a tiempo real de pacientes ingresados con función renal alterada, denominado proyecto DETECT-H. El FRA se estableció de acuerdo con las guías KDIGO. Resultados: En 6 meses, 1.241 alertas fueron recogidas de 11.022 ingresos. La incidencia global del FRA fue del 7,7%. La distribución en función del estadio máximo del FRA alcanzado fue: estadio 1: 49,8%, estadio 2: 24,5% y estadio 3: 25,8%; con una mortalidad hospitalaria del 10,9, 22,7 y 33,9%, respectivamente. En el caso del FRA con necesidad de diálisis fue del 57,1%. La mortalidad en pacientes con enfermedad renal crónica (ERC) estable fue del 4,3%. La mediana de EH en pacientes detectados fue 8 vs. 5 días para todos los pacientes hospitalizados. El FRA se asoció con una mortalidad 3,18 (1,8-5,59) y una EH 1,52 (1,11-2,08) veces superior que aquellos ingresos sin FRA. El análisis multivariante indicó que el FRA se asociaba con la EH > 8 días.En los informes de alta, la presencia de ERC previa solo fue registrada en el 31,9% de los pacientes con ERC y el FRA hospitalario en el 45,3%. Conclusiones: La ERC y el FRA intrahospitalario son entidades infradiagnosticadas. La mortalidad y la EH están aumentadas en pacientes con disfunción renal. La gravedad del FRA se asoció con mayor mortalidad y EH. Un sistema de detección automático para identificarlos podría ser útil para mejorar estos resultados. Keywords: Acute kidney injury, Automated electronic detection system, Chronic kidney disease, Diagnosis, Health information technology, Mortality, Palabras clave: Fracaso renal agudo, Sistema de detección electrónica automática, Enfermedad renal crónica, Diagnóstico, Tecnología de información de la salud, Mortalida

Measurement of B(Ds+ -->ell+ nu) and the Decay Constant fDs From 600/pb of e+e- Annihilation Data Near 4170 MeV

We examine e+e- --> Ds^-D_s^{*+} and Ds^{*-}Ds^{+} interactions at 4170 MeV using the CLEO-c detector in order to measure the decay constant fDs with good precision. Previously our measurements were substantially higher than the most precise lattice based QCD calculation of (241 +/- 3) MeV. Here we use the D_s^+ --> ell^+ nu channel, where the ell^+ designates either a mu^+ or a tau^+, when the tau^+ --> pi^+ anti-nu. Analyzing both modes independently, we determine B(D_s^+ --> mu^+ nu)= 0.565 +/- 0.045 +/- 0.017)%, and B(D_s^+ --> mu^+ nu)= (6.42 +/- 0.81 +/- 0.18)%. We also analyze them simultaneously to find an effective value of B^{eff}(D_s^+ --> mu^+ nu)= (0.591 +/- 0.037 +/- 0.018)% and fDs=(263.3 +/- 8.2 +/- 3.9) MeV. Combining with the CLEO-c value determined independently using D_s^+ --> tau^+ nu, tau^+ --> e^+ nu anti-nu decays, we extract fDs=(259.5 +/- 6.6 +/- 3.1) MeV. Combining with our previous determination of B(D^+ --> mu^+ nu), we extract the ratio fDs/fD+=1.26 +/- 0.06 +/- 0.02. No evidence is found for a CP asymmetry between Gamma(D_s^+ --> mu^+\nu) and \Gamma(D_s^- --> mu^- nu); specifically the fractional difference in rates is measured to be (4.8 +/- 6.1)%. Finally, we find B(D_s^+ --> e^+ nu) < 1.2x10^{-4} at 90% confidence level.Comment: 26 pages, 16 figure