• abnormal sodium burden
• heart failure with preserved ejection fraction
• prognosis

• Humans
• Cardiovascular Diseases
• Heart Failure
• Hospitalization
• Mineralocorticoid Receptor Antagonists/therapeutic use
• Prognosis
• Sodium
• Spironolactone/therapeutic use
• Stroke Volume
• Clinical Trials as Topic

• 202201011014 Guangzhou Municipal Science and Technology Project
• 82100387 National Natural Science Foundation of China
• 82200415 National Natural Science Foundation of China
• 82270399 National Natural Science Foundation of China
• 2022A1515010227 Science Fund for Distinguished Young Scholars of Guangdong Province
• 2022A1515010785 Science Fund for Distinguished Young Scholars of Guangdong Province
• 2022A1515012161 Science Fund for Distinguished Young Scholars of Guangdong Province
• 2021A1515010114 Basic and Applied Basic Research Foundation of Guangdong Province

• Ejection fraction
• Heart failure
• Hospitalization
• MELD
• Prognosis

• Humans
• Heart-Assist Devices/adverse effects
• Hyponatremia/etiology
• Heart Failure/complications
• Heart Failure/surgery
• Prognosis
• Sodium
• Retrospective Studies
• Treatment Outcome

• K12 HS026385 AHRQ HHS
• K23 HL155970 NHLBI NIH HHS

• Heart failure
• Hypernatremia
• Hyponatremia
• Sodium levels
• Survival
• Trajectory

• Fluid overload
• Hemodialysis
• Hyperglycemia
• Hyponatremia
• Major adverse cardiovascular events
• Malnutrition
• Mortality

Sodium level is an important clinical predictor of complex biliary disease. Hyponatremia has been observed in conjunction with biliary disease, however the nature of this association remains unclear.

To investigate the association between serum sodium and severe biliary disease.

Of 920 patients with gallstone disease treated at the SFVA Hospital from 1989-2019 were studied. We conducted multivariate analyses of correlation between sodium level and biliary disease severity, the presence/location of biliary bacteria, and other factors. Minimum sodium level pre-intervention was collected. Gallstones, bile, and blood (as relevant) were cultured. Illness severity was characterized: (1) None (no infectious manifestations); (2) Systemic inflammatory response syndrome; (3) Severe illness (gangrenous cholecystitis, cholangitis, necrotizing pancreatitis); and (4) Multiple organ dysfunction syndrome (bacteremia, hypotension, organ failure). Comorbidity was defined using the Charlson Comorbidity Index (CCI).

Decreased sodium level significantly correlated with worsening illness severity, ascending bacterial infection, gangrenous changes, elevated CCI score, increasing age, male sex, and glucose. On multivariate analysis, all factors, except age, gender and glucose, independently correlated with sodium level and factors were additive.

This unique study is the first to explore, with such granularity, the relationship between biliary disease and sodium. No prior studies have examined specific culture and clinical data. It illustrates an inverse, independent correlation between illness severity and sodium. Culture data demonstrate that sodium decreases as infection ascends from gallstone colonization to bactibilia to bacteremia. Patient comorbidity and gangrenous changes also independently correlate with sodium on multivariate analysis. Sodium level is an important clinical indicator of disease severity for patients with biliary disease.

• Hyponatremia
• Biliary disease
• Cholecystitis
• Cholangitis
• Sodium
• Sepsis

• heart failure
• hyponatremia
• stemi

• Adult
• Aged
• Cohort Studies
• Ethiopia/epidemiology
• Female
• Heart Failure/blood
• Heart Failure/complications
• Heart Failure/mortality
• Humans
• Hyponatremia/blood
• Hyponatremia/complications
• Hyponatremia/epidemiology
• Kaplan-Meier Estimate
• Male
• Middle Aged
• Prevalence
• Prognosis
• Retrospective Studies
• Sodium/blood

• Hyponatremia
• fluid restriction
• heart failure
• hospital cost
• hospital length of stay
• tolvaptan

• echocardiography
• heart failure

• Arginine vasopressin
• Copeptin
• Heart failure
• Vasopressin receptor antagonist

• Heart failure
• Mortality
• Patient readmission
• Risk factors
• Sodium

• Aged
• Female
• Heart Failure/complications
• Heart Failure/mortality
• Hospitalization
• Humans
• Hyponatremia/complications
• Hyponatremia/mortality
• Hyponatremia/therapy
• Male
• Patient Readmission/statistics & numerical data
• Prognosis
• Retrospective Studies
• Risk Factors

Hyponatremia is a common electrolyte abnormality in patients with heart failure (HF). It is independently associated with increased short-term and long-term morbidity and mortality. The main objective of this study was to assess patterns of hyponatremia and its association with discharge outcomes in patients with HF admitted to a teaching hospital in Ethiopia.

This is a descriptive, prospective, hospital-based cohort study of patients with HF admitted to Jimma University Hospital, Ethiopia, between November 1, 2013 and July 31, 2014. A structured questionnaire was used to collect information on sociodemographic characteristics, clinical profile at admission, and outcomes at discharge. Plasma sodium concentration was analyzed at admission for all patients. The relationship between hyponatremia at admission and in-hospital mortality, as well as length of hospital stay, was assessed using both bivariate analysis and multivariable logistic regressions. The level of statistical significance was set at P<0.05.

Of 152 participants admitted with HF, 44 (28.9%) had hyponatremia, which is defined as serum sodium level <135 mmol/L. Patients on salt restriction, on chronic diuretic treatment (furosemide and spironolactone), and with impaired renal function at admission were found to be highly affected. Hyponatremia was found to be associated with increased in-hospital mortality (P=0.008) and longer hospital stay (16.6 vs 12 days, P<0.001). Patients with hyponatremia also had lower blood pressure and poor functional status at discharge.

This study demonstrates that hyponatremia is highly prevalent in patients hospitalized with HF and is associated with increased in-hospital mortality and longer hospital stay. Thus, great emphasis should be given to identify high-risk patients, and prevention and early detection of hyponatremia to prevent its deleterious effects. Large-scale national studies are also needed to complement our findings.

• Africa
• Ethiopia
• heart failure
• hyponatremia
• outcome

• AVP
• Biomarker
• Copeptin
• Heart failure
• Hyponatremia
• Neurohormonal activation
• Osmoregulation
• Vasopressin

• Peritoneal dialysis
• cardiorenal
• elderly
• heart failure
• ultrafiltration

Heart failure is a disease predominantly caused by an energy metabolic disorder in cardiomyocytes. The present study investigated the inhibitory effects of fenofibrate (FF) on isoproterenol (ISO)-induced hear failure in rats, and examined the underlying mechanisms. The rats were divided into CON, ISO (HF model), FF and FF+ISO (HF animals pretreated with FF) groups. The cardiac structure and function of the rats were assessed, and contents of free fatty acids and glucose metabolic products were determined. In addition, myocardial cells were isolated from neonatal rats and used in vitro to investigate the mechanisms by which FF relieves heart failure. Western blot analysis was performed to quantify the expression levels of peroxisome proliferator-activated receptor (PPAR)α and uncoupling protein 2 (UCP2). FF effectively alleviated the ISO-induced cardiac structural damage, functional decline, and fatty acid and carbohydrate metabolic abnormalities. Compared with the ISO group, the serum levels of brain natriuretic peptide (BNP), free fatty acids, lactic acid and pyruvic acid were decreased in the FF animals. In the cultured myocardial cells, lactic acid and pyruvic acid contents were lower in the supernatants obtained from the FF animals, with lower levels of mitochondrial ROS production and cell necrosis, compared with the ISO group, whereas PPARα upregulation and UCP2 downregulation occurred in the FF+ISO group. The results demonstrated that FF efficiently alleviated heart failure in the ISO-induced rat model, possibly via promoting fatty acid oxidation.

To date, the majority of studies on hyponatremia focussed on hyponatremia at admission, and came from developed countries. This study aimed to identify the prevalence of hyponatremia during hospitalization in patients hospitalized for HF and its association with in-hospital mortality.

This was an observational study using retrospective data from patients’ records between 2010–2013. It focused on those patients carrying an ICD-10 code of 150.0(Congestive Heart Failure) as their primary diagnosis.

Hyponatremia during hospitalization was defined as serum sodium level lower than 135 mEq/L obtained from a blood chemistry measurement on the next days after admission. Patients’ characteristics were examined and the association between hyponatremia during hospitalization and in-hospital mortality was analyzed.

Among 464 patients hospitalized for HF, hyponatremia during hospitalization was observed in 22 % of patients with 44 % of this group had normal serum sodium level on admission.

Hyponatremia during hospitalization was associated with lower blood pressure on admission, both systolic and diastolic, peripheral oedema, ascites and fatigue. Patients having history of hospitalization for cardiac diseases and renal failure were higher in patients developing hyponatremia during hospitalization. In this group, amiodarone, heparin, insulin and antibiotics were administered more frequently. Factors potentially increase the risk of hyponatremia during hospitalization include history of fatigue (OR = 3.23, 95 % CI 1.79–5.82), presence of ascites (4.14, 1.84–9.31), and administration of heparin (3.85, 1.78–8.31) and antibiotics (3.08, 1.71–5.53). Length of hospital stay was significantly longer in patients with hyponatremia during hospitalization and in-hospital mortality was also higher compared to non-hyponatremic patients, 7.7 % and 29.1 %, respectively.

This study found that the prevalence of hyponatremia during hospitalization in patients hospitalized for HF was almost the same as hyponatremia on admission and administration of heparin and antibiotics can potentially worsen hyponatremia during hospitalization. In this study population, hyponatremia during hospitalization was found to be associated with in-hospital mortality.

Cardiovascular (CV) disease is the leading cause of morbidity and mortality in patients on peritoneal dialysis (PD). Hyponatremia was recently shown to be a modifiable factor that is strongly associated with increased mortality in PD patients. However, the clinical impact of hyponatremia on CV outcomes in these patients is unclear.

To determine whether a low serum sodium level predicts the development of CV disease, we carried out a prospective observational study of 441 incident patients who started PD between January 2000 and December 2005. Time-averaged serum sodium (TA-Na) levels were determined to investigate the ability of hyponatremia to predict newly developed CV events in these patients.

During a mean follow-up of 43.2 months, 106 (24.0%) patients developed new CV events. The cumulative incidence of new-onset CV events after the initiation of PD was significantly higher in patients with TA-Na levels ≤ 138 mEq/L than in those with a TA-Na > 138 mEq/L. After adjustment for multiple potentially confounding covariates, an increase in TA-Na level was found to be associated with a significantly lower risk of CV events (subdistribution hazard ratio per 1 mEq/L increase, 0.90; 95% confidence interval, 0.83–0.96; p = 0.003). Patients with a TA-Na ≤ 138 mEq/L had a 2.31-fold higher risk of suffering a CV event.

These results provide evidence of a clear association between low serum sodium and new-onset CV events after dialysis initiation in PD patients. Whether the correction of hyponatremia for this indication provides additional protection for the development of CV disease in these patients remains to be addressed in interventional studies.

• Cardiovascular Diseases/etiology
• Humans
• Hyponatremia/complications
• Incidence
• Multivariate Analysis
• Peritoneal Dialysis
• Proportional Hazards Models
• Risk Factors

Organisms across the tree of life use a variety of mechanisms to respond to stress-inducing fluctuations in osmotic conditions. Cellular response mechanisms and phenotypes associated with osmoadaptation also play important roles in bacterial virulence, human health, agricultural production and many other biological systems. To improve understanding of osmoadaptive strategies, we have generated 59 high-quality draft genomes for the haloarchaea (a euryarchaeal clade whose members thrive in hypersaline environments and routinely experience drastic changes in environmental salinity) and analyzed these new genomes in combination with those from 21 previously sequenced haloarchaeal isolates. We propose a generalized model for haloarchaeal management of cytoplasmic osmolarity in response to osmotic shifts, where potassium accumulation and sodium expulsion during osmotic upshock are accomplished via secondary transport using the proton gradient as an energy source, and potassium loss during downshock is via a combination of secondary transport and non-specific ion loss through mechanosensitive channels. We also propose new mechanisms for magnesium and chloride accumulation. We describe the expansion and differentiation of haloarchaeal general transcription factor families, including two novel expansions of the TATA-binding protein family, and discuss their potential for enabling rapid adaptation to environmental fluxes. We challenge a recent high-profile proposal regarding the evolutionary origins of the haloarchaea by showing that inclusion of additional genomes significantly reduces support for a proposed large-scale horizontal gene transfer into the ancestral haloarchaeon from the bacterial domain. The combination of broad (17 genera) and deep (≥5 species in four genera) sampling of a phenotypically unified clade has enabled us to uncover both highly conserved and specialized features of osmoadaptation. Finally, we demonstrate the broad utility of such datasets, for metagenomics, improvements to automated gene annotation and investigations of evolutionary processes.

The ability to adjust to changing osmotic conditions (osmoadaptation) is crucial to the survival of organisms across the tree of life. However, significant gaps still exist in our understanding of this important phenomenon. To help fill some of these gaps, we have produced high-quality draft genomes for 59 osmoadaptation “experts” (extreme halophiles of the euryarchaeal family Halobacteriaceae). We describe the dispersal of osmoadaptive protein families across the haloarchaeal evolutionary tree. We use this data to suggest a generalized model for haloarchaeal ion transport in response to changing osmotic conditions, including proposed new mechanisms for magnesium and chloride accumulation. We describe the evolutionary expansion and differentiation of haloarchaeal general transcription factor families and discuss their potential for enabling rapid adaptation to environmental fluxes. Lastly, we challenge a recent high-profile proposal regarding the evolutionary origins of the haloarchaea by showing that inclusion of additional genomes significantly reduces support for a proposed large-scale horizontal gene transfer into the ancestral haloarchaeon from the bacterial domain. This result highlights the power of our dataset for making evolutionary inferences, a feature which will make it useful to the broader evolutionary community. We distribute our genomic dataset through a user-friendly graphical interface.

• Aged
• Cause of Death
• Female
• Follow-Up Studies
• Heart Failure/complications
• Heart Failure/mortality
• Heart Failure/physiopathology
• Hospitalization/trends
• Humans
• Hyponatremia/blood
• Hyponatremia/epidemiology
• Hyponatremia/etiology
• Incidence
• Male
• Outpatients
• Prevalence
• Prognosis
• Proportional Hazards Models
• Retrospective Studies
• Risk Factors
• Sodium/blood
• Stroke Volume/physiology
• Survival Rate/trends
• Time Factors
• United States/epidemiology
• Ventricular Function, Left/physiology
• Veterans

• Hospitalised patients
• Hyponatraemia
• In-hospital mortality
• Internal department

• Adult
• Age Factors
• Aged
• Aged, 80 and over
• Female
• Hospital Mortality
• Humans
• Hyponatremia/mortality
• Male
• Middle Aged
• Multivariate Analysis
• Retrospective Studies
• Risk Factors
• Young Adult

Twenty-one non-peptide substituted desloratadine class compounds were synthesized as novel arginine vasopressin receptor antagonists from desloratadine via successive acylation, reduction and acylation reactions. Their structures were characterized by ¹H-NMR and HRMS, their biological activity was evaluated by in vitro and in vivo studies. The in vitro binding assay and cAMP accumulation assay indicated that these compounds are potent selective V2 receptor antagonists. Among them compounds 1n, 1t and 1v exhibited both high affinity and promising selectivity for V2 receptors. The in vivo diuretic assay demonstrated that 1t presented remarkable diuretic activity. In conclusion, 1t is a potent novel AVP V2 receptor antagonist candidate.

• Antidiuretic hormone
• Aquaretics
• Hypo-osmolality
• Natriuresis
• Syndrome of inappropriate antidiuretic hormone secretion
• Vasopressin
• Volume regulation

The present review analyses the mechanisms relating heart failure and hyponatremia, describes the association of hyponatremia with the progress of disease and morbidity/mortality in heart failure patients and presents treatment options focusing on the role of arginine vasopressin (AVP)-receptor antagonists. Hyponatremia is the most common electrolyte disorder in the clinical setting and in hospitalized patients. Patients with hyponatremia may have neurologic symptoms since low sodium concentration produces brain edema, but the rapid correction of hyponatremia is also associated with major neurologic complications. Patients with heart failure often develop hyponatremia owing to the activation of many neurohormonal systems leading to decrease of sodium levels. A large number of clinical studies have associated hyponatremia with increased morbidity and mortality in patients hospitalized for heart failure or outpatients with chronic heart failure. Treatment options for hyponatremia in heart failure, such as water restriction or the use of hypertonic saline with loop diuretics, have limited efficacy. AVP-receptor antagonists increase sodium levels effectively and their use seems promising in patients with hyponatremia. However, the effects of AVP-receptor antagonists on hard outcomes in patients with heart failure and hyponatremia have not been thoroughly examined.

• Heart failure
• Hyponatremia
• Sodium
• Vasopressin
• Vasopressin-receptor antagonists
• Tolvaptan
• Conivaptan
• Lixivaptan

• Heart failure
• Hyponatremia
• Outcomes
• Prognosis
• Sodium