The occurrence of hyponatremia and its importance as a prognostic factor in a cross-section of cancer patients

BACKGROUND: Hyponatremia is prognostic of higher mortality in some cancers but has not been well studied in others. We used a longitudinal design to determine the incidence and prognostic importance of euvolemic and hypervolemic hyponatremia in patients following diagnosis with lymphoma, breast (BC), colorectal (CRC), small cell lung (SCLC), or non-small cell lung cancer (NSCLC). METHODS: Medical record and tumor registry data from two large integrated delivery networks were combined for patients diagnosed with lymphoma, BC, CRC, or lung cancers (2002-2010) who had ≥1 administration of radiation/chemotherapy within 6 months of diagnosis and no evidence of hypovolemic hyponatremia. Hyponatremia incidence was measured per 1000 person-years (PY). Cox proportional hazard models assessed the prognostic value of hyponatremia as a time-varying covariate on overall survival (OS) and progression-free survival (PFS). RESULTS: Hyponatremia incidence (%, rate) was 76 % each, 1193 and 2311 per 1000 PY, among NSCLC and SCLC patients, respectively; 37 %, 169 in BC; 64 %, 637 in CRC, and 60 %, 395 in lymphoma. Hyponatremia was negatively associated with OS in BC (HR 3.7; P = \u3c.01), CRC (HR 2.4; P \u3c .01), lung cancer (HR 2.4; P \u3c .01), and lymphoma (HR 4.5; P \u3c .01). Hyponatremia was marginally associated with shorter PFS (HR 1.3, P = .07) across cancer types. CONCLUSIONS: The incidence of hyponatremia is higher than previously reported in lung cancer, is high in lymphoma, BC, and CRC and is a negative prognostic indicator for survival. Hyponatremia incidence in malignancy may be underestimated. The effects of hyponatremia correction on survival in cancer patients require further study

Analysis of Synthetic Monodisperse Polysaccharides by Wide Mass Range Ultrahigh-Resolution MALDI Mass Spectrometry

Carbohydrates, such as oligo- and polysaccharides, are highly abundant biopolymers that are involved in numerous processes. The study of their structure and functions is commonly based on a material that is isolated from complex natural sources. However, a more precise analysis requires pure compounds with well-defined structures that can be obtained from chemical or enzymatic syntheses. Novel synthetic strategies have increased the accessibility of larger monodisperse polysaccharides, posing a challenge to the analytical methods used for their molecular characterization. Here, we present wide mass range ultrahigh-resolution matrix-assisted laser desorption/ionization (MALDI) Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometry (MS) as a powerful platform for the analysis of synthetic oligo- and polysaccharides. Synthetic carbohydrates 16-, 64-, 100-, and 151-mers were mass analyzed and characterized by MALDI in-source decay FT-ICR MS. Detection of fragment ions generated from glycosidic bond cleavage (or cross-ring cleavage) provided information of the monosaccharide content and the linkage type, allowing for the corroboration of the carbohydrate compositions and structures

Analysis of synthetic monodisperse polysaccharides by wide mass range ultrahigh-resolution MALDI mass spectrometry

Carbohydrates, such as oligo- and polysaccharides, are highly abundant biopolymers that are involved in numerous processes. The study of their structure and functions is commonly based on a material that is isolated from complex natural sources. However, a more precise analysis requires pure compounds with well-defined structures that can be obtained from chemical or enzymatic syntheses. Novel synthetic strategies have increased the accessibility of larger monodisperse polysaccharides, posing a challenge to the analytical methods used for their molecular characterization. Here, we present wide mass range ultrahigh-resolution matrix-assisted laser desorption/ionization (MALDI) Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometry (MS) as a powerful platform for the analysis of synthetic oligo- and polysaccharides. Synthetic carbohydrates 16-, 64-, 100-, and 151-mers were mass analyzed and characterized by MALDI in-source decay FT-ICR MS. Detection of fragment ions generated from glycosidic bond cleavage (or cross-ring cleavage) provided information of the monosaccharide content and the linkage type, allowing for the corroboration of the carbohydrate compositions and structures.Proteomic

Role of Kv1 Potassium Channels in Regulating Dopamine Release and Presynaptic D2 Receptor Function

Dopamine (DA) release in the CNS is critical for motor control and motivated behaviors. Dysfunction of its regulation is thought to be implicated in drug abuse and in diseases such as schizophrenia and Parkinson's. Although various potassium channels located in the somatodendritic compartment of DA neurons such as G-protein-gated inward rectifying potassium channels (GIRK) have been shown to regulate cell firing and DA release, little is presently known about the role of potassium channels localized in the axon terminals of these neurons. Here we used fast-scan cyclic voltammetry to study electrically-evoked DA release in rat dorsal striatal brain slices. We find that although G-protein-gated inward rectifying (GIRK) and ATP-gated (KATP) potassium channels play only a minor role, voltage-gated potassium channels of the Kv1 family play a major role in regulating DA release. The use of Kv subtype-selective blockers confirmed a role for Kv1.2, 1.3 and 1.6, but not Kv1.1, 3.1, 3.2, 3.4 and 4.2. Interestingly, Kv1 blockers also reduced the ability of quinpirole, a D2 receptor agonist, to inhibit evoked DA overflow, thus suggesting that Kv1 channels also regulate presynaptic D2 receptor function. Our work identifies Kv1 potassium channels as key regulators of DA release in the striatum

Management Strategies and Outcomes for Hyponatremia in Cirrhosis in the Hyponatremia Registry

Aim. Treatment practices and effectiveness in cirrhotic patients with hyponatremia (HN) in the HN Registry were assessed. Methods. Characteristics, treatments, and outcomes were compared between patients with HN at admission and during hospitalization. For HN at admission, serum sodium concentration [Na] response was analyzed until correction to > 130 mmol/L, switch to secondary therapy, or discharge or death with sodium ≤ 130 mmol/L. Results. Patients with HN at admission had a lower [Na] and shorter length of stay (LOS) than those who developed HN (P < 0.001). Most common initial treatments were isotonic saline (NS, 36%), fluid restriction (FR, 33%), and no specific therapy (NST, 20%). Baseline [Na] was higher in patients treated with NST, FR, or NS versus hypertonic saline (HS) and tolvaptan (Tol) (P < 0.05). Treatment success occurred in 39%, 39%, 52%, 78%, and 81% of patients with NST, FR, NS, HS, and Tol, respectively. Relapse occurred in 55% after correction and was associated with increased LOS (9 versus 6 days, P < 0.001). 34% admitted with HN were discharged with HN corrected. Conclusions. Treatment approaches for HN were variable and frequently ineffective. Success was greatest with HS and Tol. Relapse of HN is associated with increased LOS

The emerging role of obesity in short-acting hormonal contraceptive effectiveness.

This commentary summarizes the historical landscape of short-acting CHC trials as it relates to the emerging role of obesity not only as an important factor in the outcomes of contemporary CHC trials but as a key issue to be considered by potential users and prescribers seeking the most appropriate contraceptive method for each individual woman

Current Management of Hyponatremia in Acute Heart Failure: A Report From the Hyponatremia Registry for Patients With Euvolemic and Hypervolemic Hyponatremia (HN Registry)

Hyponatremia (HN) occurs commonly in patients with acute heart failure and confers a worse prognosis. Current HN treatment varies widely, with no consensus. This study recorded treatment practices currently used for patients hospitalized with acute heart failure and HN. Data were collected prospectively from 146 US sites on patients hospitalized with acute heart failure and HN (serum sodium concentration [Na+] ≤130&nbsp;mEq/L) present at admission or developing in the hospital. Baseline variables, HN treatment, and laboratory values were recorded. Of 762 patients, median [Na+] was 126&nbsp;mEq/L (interquartile range, 7) at baseline and increased to 130&nbsp;mEq/L at discharge. Fluid restriction was the most commonly prescribed therapy (44%), followed by no specific HN treatment beyond therapy for congestion (23%), isotonic saline (5%), tolvaptan (4%), and hypertonic saline (2%). Median rate of change in [Na+] varied by treatment (0.5 [interquartile range, 1.0] to 2.3 [8.0]&nbsp;mEq/L/d) and median treatment duration ranged from 1 (interquartile range, 1) to 6 (5) days. Fluid restriction and no specific HN treatment resulted in similar changes in [Na+], and were least effective in correcting HN. Few patients (19%) had [Na+] ≥135&nbsp;mEq/L at discharge. The most commonly used treatment approaches for HN (fluid restriction and no specific treatment) in acute heart failure increased [Na+] minimally, and most patients remained hyponatremic at discharge

Diagnosing and Treating the Syndrome of Inappropriate Antidiuretic Hormone Secretion

BACKGROUND: The syndrome of inappropriate antidiuretic hormone secretion is the most common cause of hyponatremia in clinical practice, but current management of hyponatremia and outcomes in patients with syndrome of inappropriate antidiuretic hormone secretion are not well understood. The objective of the Hyponatremia Registry was to assess the current state of management of hyponatremia due to syndrome of inappropriate antidiuretic hormone secretion in diverse hospital settings, specifically which diagnostic and treatment modalities are currently used and how rapidly and reliably they result in an increase in serum sodium concentration ([Na+]). A secondary objective was to determine whether treatment choices and outcomes differ across the United States and the European Union. METHODS: The Hyponatremia Registry recorded selected diagnostic measures and use, efficacy, and outcomes of therapy for euvolemic hyponatremia diagnosed clinically as syndrome of inappropriate antidiuretic hormone secretion in 1524 adult patients with [Na+] = 5 mEq/L in 55% and 64% of monotherapy treatment episodes, respectively. Appropriate laboratory tests to diagnose syndrome of inappropriate antidiuretic hormone secretion were obtained in <50% of patients; success rates in correcting hyponatremia were significantly higher when such tests were obtained. Few outcome differences were found between the United States and the European Union. A notable exception was hospital length of stay; use of tolvaptan was associated with significantly shorter length of stay in the European Union but not in the United States. Despite the availability of effective therapies, most patients with syndrome of inappropriate antidiuretic hormone secretion were discharged from the hospital still hyponatremic. (C) 2016 Elsevier Inc. All rights reserved