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Introduction: Severe hypernatremia is a critical situation, and when coupled with intravascular depletion and hypotension can create a treatment dilemma.Case Report: We present the case of a medically complex patient who had gradually worsening alteration of mental status and mean arterial pressures in the 50s on presentation to the emergency department.Conclusion: Final diagnoses included severe hypernatremia and hypovolemic shock secondary to poor oral intake. We used judicious fluid repletion with gradual improvement in sodium levels and permissive hypotension to avoid rapid osmotic shifts. Balancing reperfusion and the risk for osmotic effects of aggressive fluid resuscitation can be a challenging situation for the multidisciplinary team.

In hyperglycemia, the serum sodium concentration ([Na]S) receives influences from (a) the fluid exit from the intracellular compartment and thirst, which cause [Na]S decreases; (b) osmotic diuresis with sums of the urinary sodium plus potassium concentration lower than the baseline euglycemic [Na]S, which results in a [Na]S increase; and (c), in some cases, gains or losses of fluid, sodium, and potassium through the gastrointestinal tract, the respiratory tract, and the skin. Hyperglycemic patients with hypernatremia have large deficits of body water and usually hypovolemia and develop severe clinical manifestations and significant mortality. To assist with the correction of both the severe dehydration and the hypovolemia, we developed formulas computing the fractional losses of the body water and monovalent cations in hyperglycemia. The formulas estimate varying losses between patients with the same serum glucose concentration ([Glu]S) and [Na]S but with different sums of monovalent cation concentrations in the lost fluids. Among subjects with the same [Glu]S and [Na]S, those with higher monovalent cation concentrations in the fluids lost have higher fractional losses of body water. The sum of the monovalent cation concentrations in the lost fluids should be considered when computing the volume and composition of the fluid replacement for hyperglycemic syndromes.

A 9‐month‐old male presented with vomiting and dehydration with mild hypernatremia in the context of failure to thrive. He was later diagnosed with nephrogenic diabetes insipidus (NDI) during this hospitalisation and was also found to have eosinophilic esophagitis (EoE). He has since been growing well after EoE and NDI were properly managed. Molecular genetic testing revealed an unreported deletion in AQP2 which was deemed pathogenic and of autosomal dominant inheritance when correlated with his clinical findings and family history. This case report describes the clinical course of this patient in comparison to his family members and reviews current literature on autosomal dominant NDI caused by AQP2 mutations. [ABSTRACT FROM AUTHOR]

Hypernatremia is an increase in serum sodium concentration above 145 mmol/L. There are many causes of elevated sodium levels in the blood serum. One is incorrect actions performed by medical staff. The symptoms of excessively high serum sodium levels depend on the severity of hypernatremia, the rate of its increase and the accompanying volume disorders. Severe symptoms include altered consciousness, increased muscle tone and reflexes, convulsions, psychomotor hyperactivity or drowsiness (up to coma), respiratory failure, and even death. We present the case of a 45‐year‐old man who took seven tablets of a blood pressure‐lowering drug, and paramedics subsequently administered a concentrated solution of table salt to induce vomiting. However, vomiting did not occur, leading to hypernatremia. Ultimately, the man survived but developed persistent cognitive dysfunction, including disordered short‐term memory and encoding and retrieval of information from long‐term memory, weakening of attention function and fatigue, and disorders in abstract thinking. The patient's family went to the prosecutor's office to investigate the possibility of medical malpractice. Experts found that the paramedics' actions were incorrect. Although it has been known for many years that table salt solutions should not be used to induce vomiting, unfortunately, both laypeople and medical professionals are still using this technique. Iatrogenic salt poisoning may end not only in serious health complications but also in legal consequences. [ABSTRACT FROM AUTHOR]

Regional citrate anticoagulation (RCA) is a preferred method for continuous renal replacement therapy (CRRT) due to its benefits of extended filter lifespan and reduced bleeding complications. However, RCA can cause metabolic side effects such as alkalosis, acidosis, hypotension, and electrolyte imbalances. Optimal anticoagulation requires careful adjustment of citrate infusion based on blood flow rate. Citrate accumulation can occur in certain conditions, leading to adverse effects. Strategies for adapting citrate anticoagulation include adjusting the dose based on the patient's condition. The Cori cycle has been proposed as an alternative pathway for citrate metabolism outside the liver mitochondria. Establishing thresholds for citrate initiation is important, and lactate levels can be used as an indicator of impaired citrate metabolism. The proposed hypothesis of an alternative inducible citrate metabolism pathway requires further research, including an animal model, to validate its effectiveness. Overall, RCA is a viable option for patients with liver failure, and further research is needed to optimize its application and improve anticoagulation strategies in various clinical contexts. [Extracted from the article]

Dysnatremia is common in donors and recipients of liver transplantation (LT). However, the influence of dysnatremia on LT prognosis remains controversial. This study aimed to investigate effects of donors' and recipients' serum sodium on LT prognosis. We retrospectively reviewed 248 recipients who underwent orthotopic LT at our center between January 2016 and December 2018. Donors and recipients perioperative and 3-year postoperative clinical data were included. Delta serum sodium was defined as the donors' serum sodium minus the paired recipients' serum sodium. Donors with serum sodium > 145 mmol/L had significantly higher preoperative blood urea nitrogen (BUN) (P < 0.01) and creatinine (Cr) (P < 0.01) than others. Preoperative total bilirubin (TBIL) (P < 0.01), direct bilirubin (DBIL) (P < 0.01), BUN (P < 0.01), Cr (P < 0.01) were significantly higher in the hyponatremia group of recipients than the other groups, but both of donors' and recipients' serum sodium had no effect on the LT prognosis. In the delta serum sodium < 0 mmol/L group, TBIL (P < 0.01) and DBIL (P < 0.01) were significantly higher in postoperative 1 week than the other groups, but delta serum sodium had no effect on the postoperative survival rates. Dysnatremia in donors and recipients of LT have no effect on postoperative survival rates, hepatic and renal function, but recipients with higher serum sodium than donors have significantly higher TBIL and DBIL at 1 week postoperatively. [ABSTRACT FROM AUTHOR]

Intravenous fluids are commonly prescribed to children in hospitals. However, there are risks associated with their use. In order to safely prescribe these clinicians should understand the indications for their use, the principles underpinning their use and know the likely complications associated with intravenous fluid administration in children. Intravenous fluids should be prescribed depending on individual needs of each child and with careful monitoring and re-assessment. This review aims to provide a general approach to fluid prescription in children, providing some background of different physiological principles, different fluid composition, and the role of anti-diuretic hormone in fluid homeostasis. Fluid prescription is discussed, with an approach taking into consideration resuscitation boluses, dehydration, replacing ongoing losses and maintenance requirements. Case examples are provided to further facilitate readers' comprehension. Electrolyte abnormalities and an approach to the management of deranged electrolytes is addressed. Complications associated with fluid administration are highlighted, in particular, emphasizing the assessment and emergency management of the child with suspected cerebral oedema or hyponatraemic encephalopathy. Special consideration and discussion is given to the differing approach to fluid management of children in the setting of burns or diabetic ketoacidosis. [ABSTRACT FROM AUTHOR]

This article provides a comprehensive overview of electrolyte and water homeostasis in pediatric patients, focusing on some of the common serum electrolyte abnormalities encountered in clinical practice. Understanding pathophysiology, taking a detailed history, performing comprehensive physical examinations, and ordering basic laboratory investigations are essential for the timely proper management of these conditions. We will discuss the pathophysiology, clinical manifestations, diagnostic approaches, and treatment strategies for each electrolyte disorder. This article aims to enhance the clinical approach to pediatric patients with electrolyte imbalance-related emergencies, ultimately improving patient outcomes. Trial registration This manuscript does not include a clinical trial; instead, it provides an updated review of literature. [ABSTRACT FROM AUTHOR]

Pathogenic variants in hnRNPA1 have been reported in amyotrophic lateral sclerosis (ALS) patients. However, studies on hnRNPA1 mutant spectrum and pathogenicity of variants were rare. We performed whole exome sequencing of ALS-associated genes and subsequent verification of rare variants in hnRNPA1 in our ALS patients. The hnRNPA1 mutations reported in literature were reviewed and combined with our results to determine the genotype-phenotype relationship. Functional analysis of the novel variant p.G195A was performed in vitro by transfection of mutant hnRNPA1 into 293T cell. Among 207 ALS patients recruited, 3 rare hnRNPA1 variants were identified (mutant frequency 1.45%), including two recurrent mutations (p.P340S and p.G283R), and a novel rare variant p.G195A. In combination with previous reports, there are 27 ALS patients with 15 hnRNPA1 mutations identified. Disease onset age was 47.90 ± 1.52 years with predominant limb onset. The p.P340S mutation caused flail arm syndrome (FAS) in two independent families with extended life expectancy. The newly identified p.G195A mutation, lying at the start of the PrLD ("prion-like" domain)/LCD (low-complexity domain), causes local structural changes in 3D protein prediction. Upon sodium arsenite exposure, mutant hnRNPA1 retained in the nucleus but deficit of cytoplasmic G3BP1-positive stress granule clearance was observed. This is different from the p.P340S mutation which caused both cytoplasmic translocation and stress granule formation. No cytoplasmic TDP-43 translocation was observed. Mutations in hnRNPA1 are overall minor in ALS patients. The p.P340S mutation is associated with manifestation of FAS. Mutations in LCD of hnRNPA1 cause stress granule misprocessing. [ABSTRACT FROM AUTHOR]

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Background: Immune-checkpoint inhibitors (ICIs) have significantly improved metastatic renal cell carcinoma (mRCC) prognosis, although their efficacy in patients with bone metastases (BMs) remains poorly understood. We investigated the prognostic role of natremia in pretreated RCC patients with BMs receiving immunotherapy. Materials and Methods: This retrospective multicenter study included RCC patients with BMs receiving nivolumab as second-line therapy or beyond. Inclusion criteria involved baseline sodium levels (pre-ICI) and sodium levels after 4 weeks of nivolumab initiation (post-ICI). The population was divided into two groups based on the median value, and response rates, progression-free survival (PFS), and overall survival (OS) were assessed. Results: Among 120 eligible patients, those with pre-treatment sodium levels =140 mEq/L showed longer OS (18.7 vs. 12.0 months, p=0.04). Pre-treatment sodium levels =140 mEq/L were associated with better OS compared to levels <140 mE/L (18.7 vs. 12.0, p=0.04). Post-treatment sodium levels =140mEq/L were associated with improved PFS (9.6 vs. 3.2 months) and OS (25.1 vs. 8.8 months) (p=0.05 and p<0.01, respectively). Patients with consistent sodium levels =140 mEq/L at both time points exhibited the best outcomes compared to those with lower values (PFS 11.5 vs. 3.3 months and OS 42.2 vs. 9.0 months, respectively, p<0.01). Disease control rate was significantly higher in the latter group (p<0.01). Multivariate analysis confirmed the prognostic significance of sodium levels. Conclusion: Elevated sodium levels (=140 mEq/L) pre- and post-ICI treatment correlate with better survival outcomes in mRCC patients with BMs. This finding suggests sodium level assessment as a potential prognostic factor in these patients and warrants further investigation, particularly in combination immunotherapy settings. [ABSTRACT FROM AUTHOR]

Ceftazidime/avibactam (CAZ/AVI) is a combination of a well‐known third‐generation, broad‐spectrum cephalosporin with a new beta‐lactamase inhibitor that has been approved for the treatment of various infectious diseases (especially multidrug‐resistant Gram‐negative bacterial infections) by the Food and Drug Administration (FDA). The current study extensively assessed CAZ/AVI‐related adverse events (AEs) in the real world through data mining of the FDA Adverse Event Reporting System (FAERS) database to better understand toxicities. The signals of CAZ/AVI‐related AEs were quantified using disproportionality analyses, including the reporting odds ratio, the proportional reporting ratio, the Bayesian confidence propagation neural network, and the multi‐item gamma Poisson shrinker algorithms. Out of 10,114,815 records retrieved from the FAERS database, 628 cases were identified, where CAZ/AVI was implicated as the primary suspect drug. A total of 61 preferred terms with significant disproportionality that simultaneously met the criteria of all four algorithms were retained. Several unexpected safety signals may also occur, including melena, hypernatremia, depressed level of consciousness, brain edema, petechiae, delirium, and shock hemorrhagic. The median onset time for AEs associated with CAZ/AVI was 4 days, with most cases occurring within 3 days after CAZ/AVI initiation. [ABSTRACT FROM AUTHOR]

Treatment of severely hyponatremic patients with continuous renal replacement therapy (CRRT) presents a unique challenge given the lack of commercial options for hypotonic replacement solutions or dialysate. We report the case of a 55‐year‐old male who presented with profound, symptomatic hyponatremia in the setting of acute kidney injury (AKI). The patient was found to have a serum sodium concentration of 97 mEq/L because of free water retention that occurred during severe AKI from viral gastroenteritis and rhabdomyolysis. Continuous veno‐venous hemofiltration (CVVH) was required for AKI complicated by hyperkalemia, metabolic acidosis, and uremia. To prevent overcorrection of serum sodium, replacement fluids customized to natremic status had to be prepared. Conventional replacement fluid was modified on a daily basis to create hypotonic solutions with successively higher sodium concentrations. Over the course of a week, serum sodium successfully improved in a controlled and safe fashion. This case incorporates and reviews the variety of methods that have been used to safely manage severe hyponatremia with CRRT. [ABSTRACT FROM AUTHOR]

Background and Objectives: The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection may cause acute respiratory failure, but also remains responsible for many other pathologies, including electrolyte disorders. SARS-CoV-2 infection causes disorders in many systems and can disrupt water homeostasis with thirst and appetite abnormalities. Dysnatremia affects prognosis, and may be associated with mortality in patients admitted to an intensive care unit (ICU) diagnosed with SARS-CoV-2. Materials and Methods: The study included 209 patients admitted to the ICU between 12 April 2021 and 1 March 2022 who were over 18 years old and diagnosed with SARS-CoV-2 infection by clinical and thoracic tomography findings or with a positive reverse transcription polymerase chain reaction (RT-PCR) test result. The laboratory markers, treatment modalities, nutritional, and respiratory support also for outcome evaluation, length of stay in the ICU, total hospitalization duration, and mortality in the ICU were recorded. The laboratory marker comparison was made using admission with the final assessment performed before the time of mortality in the ICU or after discharge. Results: Inotropic requirements among patients were high, which reflected mortality in the ICU. Hypernatremia presence was associated with an increase in enteral support, the inotropic support requirement, and mortality. Hypernatremia was correlated with diabetes mellitus, chronic renal failure, and a longer duration under mechanical ventilation. Conclusions: Hypernatremia was an important risk factor in ICU patients hospitalized for SARS-CoV-2 infection, which was also affected by the treatment regimens given themselves. This complex relationship underlies the importance of proper electrolyte management, especially in patients who were under severe stress and organ failure. [ABSTRACT FROM AUTHOR]

Abstract Dysnatremia is common in donors and recipients of liver transplantation (LT). However, the influence of dysnatremia on LT prognosis remains controversial. This study aimed to investigate effects of donors’ and recipients’ serum sodium on LT prognosis. We retrospectively reviewed 248 recipients who underwent orthotopic LT at our center between January 2016 and December 2018. Donors and recipients perioperative and 3-year postoperative clinical data were included. Delta serum sodium was defined as the donors’ serum sodium minus the paired recipients’ serum sodium. Donors with serum sodium > 145 mmol/L had significantly higher preoperative blood urea nitrogen (BUN) (P

Abstract This article provides a comprehensive overview of electrolyte and water homeostasis in pediatric patients, focusing on some of the common serum electrolyte abnormalities encountered in clinical practice. Understanding pathophysiology, taking a detailed history, performing comprehensive physical examinations, and ordering basic laboratory investigations are essential for the timely proper management of these conditions. We will discuss the pathophysiology, clinical manifestations, diagnostic approaches, and treatment strategies for each electrolyte disorder. This article aims to enhance the clinical approach to pediatric patients with electrolyte imbalance-related emergencies, ultimately improving patient outcomes. Trial registration This manuscript does not include a clinical trial; instead, it provides an updated review of literature.

Background: Intravenous fosfomycin (IVFOF) is gaining interest in severe infections. Its use may be limited by adverse events (AEs). Little experience exists on IVFOF therapeutic drug monitoring (TDM) in real-life setting. Patients and methods: Retrospective study of patients receiving IVFOF for > 48 h at Policlinico Hospital (Milan, Italy) from 01/01/2019 to 01/01/2023. AEs associated to IVFOF graded CTCAE ≥ II were considered. Demographic and clinical risk factors for IVFOF-related AEs were analysed with simple and multivariable regression models. The determination of IVFOF TDM was made by a rapid ultraperformance liquid chromatography mass spectrometry method (LC-MS/MS) on plasma samples. The performance of TDM (trough levels (Cmin) in intermittent infusion, steady state levels (Css) in continuous infusion) in predicting AEs ≤ 5 days after its assessment was evaluated. Results: Two hundred and twenty-four patients were included. At IVFOF initiation, 81/224 (36.2%) patients were in ICU and 35/224 (15.7%) had septic shock. The most frequent infection site was the low respiratory tract (124/224, 55.4%). Ninety-five patients (42.4%) experienced ≥ 1AEs, with median time of 4.0 (2.0–7.0) days from IVFOF initiation. Hypernatremia was the most frequent AE (53/224, 23.7%). Therapy discontinuation due to AEs occurred in 38/224 (17.0%). ICU setting, low respiratory tract infections and septic shock resulted associated with AEs (RRadjusted 1.59 (95%CI:1.09–2.31), 1.46 (95%CI:1.03–2.07) and 1.73 (95%CI:1.27–2.37), respectively), while IVFOF daily dose did not. Of the 68 patients undergone IVFOF TDM, TDM values predicted overall AEs and hypernatremia with AUROC of 0.65 (95%CI:0.44–0.86) and 0.91 (95%CI:0.79-1.0) respectively for Cmin, 0.67 (95%CI:0.39–0.95) and 0.76 (95%CI:0.52-1.0) respectively for Css. Conclusions: We provided real world data on the use of IVFOF-based regimens and associated AEs. IVFOF TDM deserves further research as it may represent a valid tool to predict AEs. Key points: Real world data on intravenous fosfomycin for severe bacterial infections. AEs occurred in over 40% (therapy discontinuation in 17%) and were related to baseline clinical severity but not to fosfomycin dose. TDM showed promising results in predicting AEs. [ABSTRACT FROM AUTHOR]

OBJECTIVES: Hypernatremia may facilitate the diffusion of bilirubin through the blood-brain barrier and increase the risk of bilirubin encephalopathy. This study was conducted to compare the prognosis of jaundice infants with those with jaundice and hypernatremia. METHODS: A total of 615 term infants with idiopathic jaundice with or without hypernatremia were enrolled in this cohort study with 24-months follow-up at Ghaem Hospital, Mashhad, Iran, between 2010 and 2022. An in-house questionnaire including the laboratory evaluation and neonatal characteristics was used as the data collection tool. The follow-up of neonatal development status was performed using the Denver test II at 6, 12, 18, and 24 months after discharging from hospital. RESULTS: Normal outcomes were seen in 555 (90.2%) out of 615 studied infants, while 60 cases (9.8%) showed abnormal outcomes. Serum levels of sodium (P = 0.017), bilirubin (P = 0.001), urea (P = 0.024), and creatinine (P = 0.011) as well as hyperthermia (P = 0.046) and unconsciousness (P = 0.005) showed significant differences between the two groups. Approximately 16% of the newborns with both jaundice and hypernatremia, and 9% of those with only jaundice had unfavorable prognoses. Also, bilirubin level had the most predictive power (91.3%). CONCLUSIONS: Our results suggest that hypernatremia or jaundice alone, may affect the prognosis of infants aged 2 years; but jaundice and hypernatremia together, will intensify the developmental problems in jaundice infants. However, the role of hyperbilirubinemia in the incidence of complications is more than hypernatremia. [ABSTRACT FROM AUTHOR]

Aim: This study aimed to investigate the diagnostic and prognostic value of optic nerve sheath diameter (ONSD) measurement in patients with dysnatremia. Material and methods: This prospective clinical study included patients aged ≥18 years who were diagnosed with dysnatremia on admission to the emergency department. Results: The present study included 65 patients (35 with hypernatremia [hypernatremia group] and 30 with hyponatremia [hyponatremia group]) and 14 healthy volunteers (control group). Comparison of these groups in terms of ONSD revealed that the right and left ONSDs were significantly higher in the hypernatremia and hyponatremia groups comparing to the control group (p<0.001). According to the optimal cutoff values determined, the right ONSD detected hypernatremia with 91.4% sensitivity and 92.9% specificity and the left ONSD detected the condition with 88.6% sensitivity and 85.7% specificity. Furthermore, the right ONSD detected hyponatremia with 83.3% sensitivity and 92.9% specificity, and the left ONSD detected it with 93.0% sensitivity and 86.0% specificity. Finally, ONSD was found to be an independent predictor of mortality in patients with hypernatremia. Conclusion: ONSD is a noninvasive, easy, cheap, and reproducible measurement and can be used as an effective and powerful tool for the diagnosis of patients with dysnatremia and the prognosis of patients with hypernatremia. [ABSTRACT FROM AUTHOR]

This article discusses a case of osmotic demyelination syndrome (ODS) associated with uremia and elevated serum osmolality. The patient presented with a swollen and proptotic eye, and imaging revealed gas in the neck, skull base, and orbits. The patient developed acute tubular necrosis and hypernatremia, which contributed to the development of ODS. The article emphasizes the importance of monitoring both serum sodium and blood urea nitrogen levels to prevent neurological complications. [Extracted from the article]

Objective: Both hyponatremia and hypernatremia have been reported to occur more frequently with higher ambient temperatures, although the underlying mechanisms are not well understood. Global temperatures are rising due to climate change, which may impact the incidence of dysnatremia worldwide. We aimed to identify, collate and critically appraise studies analyzing the relationship between climate measures (outdoor temperature, humidity) and serum sodium concentrations. Design: Systematic review, reported in accordance with PRISMA guidelines. Methods: MEDLINE and Embase were searched with relevant key terms. Studies assessing the effect on serum sodium measurement of elevated temperature or humidity versus a comparator were included. Results: Of 1466 potentially relevant studies, 34 met inclusion criteria, originating from 23 countries spanning all inhabited continents. The majority (30 of 34, 88%) reported a significant association between outdoor temperature and dysnatremia, predominantly lower serum sodium with increased ambient temperature. Humidity had a less consistent effect. Individuals aged above 65 years, children, those taking diuretics and antidepressants, those with chronic renal impairment or those undertaking physical exertion had increased vulnerability to heat‐associated dysnatremia. The risk of bias was assessed to be high in all but four studies. Conclusions: Higher ambient temperature is consistently associated with an increased incidence of hyponatremia. We infer that hyponatremia presentations are likely to rise with increasing global temperatures and the frequency of extreme heat events secondary to climate change. Evidence‐based public health messages, clinician education and reduction in fossil fuel consumption are necessary to reduce the expected burden on healthcare services worldwide. [ABSTRACT FROM AUTHOR]

This article introduces an innovative teaching and learning tool called "Edelman Gamblegrams" that aims to help medical learners better understand disorders related to water/plasma tonicity homeostasis, i.e., hyponatremia and hypernatremia. Gamblegrams, named after physician James L. Gamble, are bar diagrams displaying the relative abundance of extracellular anions and cations and are commonly used in the analysis of acid-base disorders. The Edelman equation represents the physiological variables that determine plasma sodium concentration, namely, total body sodium mass, total body potassium mass, and total body water volume. Edelman Gamblegrams inspired by traditional Gamblegrams but using the components of the Edelman equation, visually demonstrate how sodium, potassium, and water contribute to plasma sodium concentration under normal and pathological conditions. Scenarios that lead to hypotonic hyponatremia and hypernatremia in Edelman Gamblegrams are also discussed. Furthermore, examples of how these visual aids can enhance understanding of the pathogenesis of dysnatremias are also presented. Overall, the use of Edelman Gamblegrams has the potential to improve comprehension and retention of concepts related to water/plasma tonicity homeostasis. NEW & NOTEWORTHY: This article introduces a new teaching tool called "Edelman Gamblegrams," modeled after the conventional Gamblegrams used in acid-base disorder analysis and using the independent physiological variables that determine the plasma sodium concentration (Edelman equation), that aims to help medical learners understand disorders related to water/plasma tonicity homeostasis. [ABSTRACT FROM AUTHOR]

Background: Clinical and experimental data on the cardiac effects of acute hypernatremia are scarce and inconsistent. We aimed to determine and understand the effects of different levels of acute hypernatremia on the human ventricular action potential. Methods: We performed computer simulations using two different, very comprehensive models of the electrical activity of a single human ventricular cardiomyocyte, i.e., the Tomek-Rodriguez model following the O'Hara-Rudy dynamic (ORd) model and the Bartolucci-Passini-Severi model as published in 2020 (known as the ToR-ORd and BPS2020 models, respectively). Mild to extreme levels of hypernatremia were introduced into each model based on experimental data on the effects of hypernatremia on cell volume and individual ion currents. Results: In both models, we observed an increase in the intracellular sodium and potassium concentrations, an increase in the peak amplitude of the intracellular calcium concentration, a hyperpolarization of the resting membrane potential, a prolongation of the action potential, an increase in the maximum upstroke velocity, and an increase in the threshold stimulus current at all levels of hypernatremia and all stimulus rates tested. The magnitude of all of these effects was relatively small in the case of mild to severe hypernatremia but substantial in the case of extreme hypernatremia. The effects on the action potential were related to an increase in the sodium-potassium pump current, an increase in the sodium-calcium exchange current, a decrease in the rapid and slow delayed rectifier potassium currents, and an increase in the fast and late sodium currents. Conclusions: The effects of mild to severe hypernatremia on the electrical activity of human ventricular cardiomyocytes are relatively small. In the case of extreme hypernatremia, the effects are more pronounced, especially regarding the increase in threshold stimulus current. [ABSTRACT FROM AUTHOR]

OBJECTIVES: To perform a detailed examination of sodium levels, hyponatremia and sodium fluctuations, and their association with delayed cerebral ischemia (DCI) and poor outcome after aneurysmal subarachnoid hemorrhage (aSAH). DESIGN: An observational cohort study from a prospective SAH Registry. SETTING: Tertiary referral center focused on SAH treatment in the Amsterdam metropolitan area. PATIENTS: A total of 964 adult patients with confirmed aSAH were included between 2011 and 2021. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 277 (29%) developed DCI. Hyponatremia occurred significantly more often in DCI patients compared with no-DCI patients (77% vs. 48%). Sodium levels, hyponatremia, hypernatremia, and sodium fluctuations did not predict DCI. However, higher sodium levels were significantly associated with poor outcome in DCI patients (DCI onset –7, DCI +0, +1, +2, +4, +5, +8, +9 d), and in no-DCI patients (postbleed day 6–10 and 12–14). Also, hypernatremia and greater sodium fluctuations were significantly associated with poor outcome in both DCI and no-DCI patients. CONCLUSIONS: Sodium levels, hyponatremia, and sodium fluctuations were not associated with the occurrence of DCI. However, higher sodium levels, hypernatremia, and greater sodium fluctuations were associated with poor outcome after aSAH irrespective of the presence of DCI. Therefore, sodium levels, even with mild changes in levels, warrant close attention. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate clinical indicators in order to examine the intensity of diabetes ketoacidosis (DKA) episodes in children and adolescents diagnosed with type 1 diabetes mellitus (T1DM). Methods: Data from 156 T1DM patients aged 6 months to 14 years, who presented with DKA to the emergency room, were retrospectively reviewed from 2018 to 2022. Data on demographic characteristics, economic status, initial clinical presentation, glycemic control, DKA severity, and laboratory evaluations were also collected. Results: Diabetes ketoacidosis episodes were more prevalent among male patients during the middle childhood age group. Notably, these episodes displayed seasonal patterns. The severity was found to be inversely associated with economic status and positively correlated with early adolescence. Newly diagnosed T1DM patients constituted 52.9%, with a statistically significant connection observed between severe DKA and this subgroup. Furthermore, there was a significant escalation in poor glycemic control with episode severity. Prolonged episode duration also exhibited a statistically significant association with more severity. Gastrointestinal symptoms were commonly reported during the presentation. Moreover, several clinical signs and symptoms, including decreased consciousness, reduced activity, drowsiness, Kussmaul breathing, shortness of breath, vomiting, tachycardia, and severe dehydration, were significantly correlated with the severity of DKA (p<0.05). Hypernatremia was more frequent among children with severe DKA. Conclusion: Diabetes ketoacidosis was observed to occur more frequently among males in middle childhood with seasonal variations. Furthermore, the severity of DKA was associated with lower economic status, early adolescence, and the presence of hypernatremia. [ABSTRACT FROM AUTHOR]

Background: Sodium fluctuation is independently associated with clinical deterioration. We developed and validated a prognostic index based on sodium fluctuation for risk stratification and in-hospital monitoring. Methods: This study included 33,323 adult patients hospitalized at a tertiary care hospital in 2014. The first 28,279 hospitalizations were analyzed to develop the model and then the validity of the model was tested using data from 5044 subsequent hospitalizations. We predict in-hospital mortality using age, comorbidity, range of sodium fluctuation, and duration of sodium fluctuation, abbreviated as CARDS. Results: In-hospital mortality was similar in the derivation (0.6%) and validation (0.4%) cohorts. In the derivation cohort, four independent risk factors for mortality were identified using logistic regression: age (66–75, 2 points; >75, 3 points); Charlson comorbidity index (>2, 5 points); range of sodium fluctuation (7–10, 4 points; >10, 10 points); and duration of fluctuation (≤3, 3 points). The AUC was 0.907 (95% CI: 0.885–0.928) in the derivation cohort and 0.932 (95% CI: 0.895–0.970) in the validation cohort. In the derivation cohort, in-hospital mortality was 0.106% in the low-risk group (0–7 points), 1.076% in the intermediate-risk group (8–14 points), and 8.463% in the high-risk group (15–21 points). In the validation cohort, in-hospital mortality was 0.049% in the low-risk group, 1.064% in the intermediate-risk group, and 8.403% in the high-risk group. Conclusions: These results suggest that patients at low, intermediate, and high risk for in-hospital mortality may be identified by CARDS mainly based on sodium fluctuation. [ABSTRACT FROM AUTHOR]

Objectives: To determine all‐cause in‐hospital mortality associated with severe hypernatraemia and the causes, comorbidities, time to treatment, discharge destination and postdischarge mortality. Design: Retrospective observational cohort study. Patients: Severe hypernatraemia, (sodium concentration ≥ 155 mmol/L), at any time during a tertiary hospital admission in Melbourne, Australia, 1 January 2019 to 31 December 2019 (pre‐COVID19). Measurements: Deaths, Charlson Comorbidity Index (CCI), hypernatraemia causes, time to treatment, discharge destination. Results: One hundred and one inpatients: 64 community‐acquired, 37 hospital‐acquired. In‐hospital mortality was 38%, but cumulative mortality was 65% by 1 month after discharge, with only a minor further increase at 6 and 12 months. After adjusting for peak sodium concentration, the community acquired group had significantly reduced odds of in‐hospital mortality (odds ratio 0.15, 95% confidence interval [0.04−0.54], p =.003). Iatrogenic factors were present in 57% (21/37) of the hospital‐acquired group. Only 55% of all cases received active sodium directed treatment. Time to start treatment did not affect outcomes. High levels of comorbidity were present, median CCI (IQR) was 6 (5−8) in the community and 5 (4−7) in the hospital group. Dementia prevalence was higher in the community group, 66% (42/64) versus 19% (7/37) (p =.001). Infection was the most common precipitant with 52% (33/64) in the community and 32% (12/37) in the hospital group. Of the survivors, 32% who had been living independently required residential care after discharge. Conclusions: Mortality was high and loss of independence in survivors common. To potentially improve outcomes, hypernatraemia‐specific guidelines should be formulated and efforts made to reduce system and iatrogenic factors. [ABSTRACT FROM AUTHOR]

Feeding disorders of infancy are common in paediatric practice. Among rare causes of this disturbance is diabetes insipidus (DI), which is a clinical syndrome characterized by polyuria, polydypsia and dehydration with hypernatraemia. Central diabetes insipidus (CDI, vasopressin deficiency) is more common in children than nephrogenic diabetes insipidus (NDI, an inability to respond adequately to vasopressin). Regardless of the type of DI, the main goal of treatment is to decrease thirst and urine output and achieve proper ion and fluid balance. We present three cases of infants with feeding difficulties. The first two cases concerned patients with semilobar holoprosencephaly (HPE). Their stories show the importance of knowing the most common abnormalities associated with HPE, such as CDI. The third child had similar problems with feeding which resembled a defect of the central nervous system, but was finally diagnosed as NDI. The diagnostic and therapeutic approach is demonstrated in the paper with special regards to safe management of hypernatraemic dehydration. [ABSTRACT FROM AUTHOR]

Background: An association between prognosis and high sodium levels in Traumatic Brain Injury (TBI) patients in Intensive Care Units (ICUs) has been noted, but limited research exists on the ideal sodium level in these patients or the impact on early mortality, using the MIMIC-IV database. Methods: A retrospective survey was conducted on TBI patients from the MIMICIV database. Patients were divided into two categories based on their highest serum sodium level within 24 h of admission exceeding 145 mmol/L: those with hypernatremia, and those with moderate-to-low sodium levels. Collected covariates encompasses demographic, clinical, laboratory, and intervention variables. A multivariate logistic regression model was implemented to forecast in-hospital mortality. Results: The study included 1749 TBI patients, with 209 (11.5%) experiencing in-hospital deaths. A non-linear test exposed an L-shaped correlation between sodium level and in-hospital mortality, with mortality rates increasing after a turning point at 144.1 mmol/L. Compared to the moderate-to-low group's 9.3% mortality rate, the hypernatremia group had a significantly higher mortality rate of 25.3% (crude odds ratio = 3.32, 95% confidence interval: 2.37 ~ 4.64, p < 0.001). After adjusting for all covariates, the hypernatremia group continued to show a significant correlation with higher mortality risk (adjusted odds ratio = 2.19, 95% confidence interval: 1.38 ~ 3.47, p = 0.001). This trend remained consistent regardless of the analyses stratification. Conclusion: The study reveals an L-shaped relationship between sodium levels and in-hospital deaths, with a pivotal point at 144.1 mmol/L. TBI patients displaying hypernatremia were independently linked to higher in-hospital mortality, underlining the need for further studies into targeted management of sodium levels in these patients. [ABSTRACT FROM AUTHOR]

Rapid-onset obesity with hypoventilation, hypothalamic dysfunction, and autonomic dysregulation (ROHHAD) is an exceptionally rare condition. This case report highlights a child diagnosed with ROHHAD syndrome, presenting with a mediastinal tumor. ROHHAD syndrome is characterized by early onset obesity, hypothalamic dysfunction, autonomic dysfunction, inadequate ventilation, suspected seizures, and abnormal behavior. The presence of a mediastinal tumor necessitated surgical intervention. Key considerations during surgery included hypernatremia due to hypothalamic dysfunction, potential airway challenges, preoperative anemia, and hemodynamic fluctuations during the removal of the sizable mediastinal tumor. Comprehensive preparations ensured a safe operation. Notably, some children with this syndrome may exhibit symptoms such as decreased gastrointestinal function, polyuria, and thermoregulatory disturbances. Vigilance is essential during anesthesia assessment in these patients. Anesthesiologists should enhance their knowledge of this condition and tailor their management strategies based on individual clinical presentations and the specific planned surgical procedures.

Background Methods Discussion Hypernatremia is a common electrolyte disturbance in hospitalised patients associated with adverse outcomes. The aetiology is diverse but often related to fluid therapy and sodium‐containing medicaments. We aim to outline the evidence base on hypernatremia in adult hospitalised patients.We will conduct a scoping review and adhere to the preferred reporting items for systematic and meta‐analysis extension for scoping reviews (PRISMA‐ScR). We will systematically search the Cochrane Library, Medline, Pubmed, and Embase from inception with no limitations to language, and include all study designs. We will use the population, exposure, comparator, and outcome‐based approach to define eligibility criteria. The population: adult hospitalised patients; exposure: hypernatremia; comparator: no hypernatremia or all types of treatments of hypernatremia; and outcomes: all reported outcomes. Two authors will independently screen and select studies followed by full‐text assessment and data extraction in duplicate. All outcome measures will be reported, and descriptive analyses will be performed. The certainty of evidence will be assessed according to an adapted grading of recommendations assessment, development, and evaluation (GRADE) approach.This scoping review will provide an overview of the current evidence regarding the incidence of hypernatremia, treatment modalities, and outcomes reported for hospitalised adult patients with hypernatremia. [ABSTRACT FROM AUTHOR]

Abstract Background Diabetes insipidus is a syndrome characterized by polyuria, which is almost always associated with polydipsia. The most frequent cause is central diabetes insipidus, which is the result of an inadequate secretion of the antidiuretic hormone, and diagnosis involves differentiating it from other causes of polyuria and polydipsia. Case presentation Here, we present a clinical case of a previously healthy 13-year-old Nepali boy, who, in December 2022, was found to have intense polydipsia accompanied by polyuria. He had bilateral lower limb weakness at the time of presentation. Biochemical evaluation demonstrated raised serum sodium (181 mEq/L), serum creatinine (78 μmol/L), and serum uric acid (560 μmol/L) with suppressed serum potassium (2.7 mEq/L), which was the major concern to the clinicians. Further laboratory workup revealed an increased serum osmolarity (393.6 mOsm/kg) with reduced urine osmolarity (222.7 mOsm/kg). On contrast magnetic resonance imaging of the brain, a thick-walled third ventricular cyst with bilateral foramen obstruction, thin membrane-like structure at top of aqueduct of Sylvius with gross obstructive hydrocephalus (inactive), and compressed and thinned pituitary gland with no bright spot was observed. The laboratory findings, radiological findings, and case presentation provided the provisional diagnosis of diabetes insipidus due to hydrocephalus and third ventricular cyst. Conclusions Central diabetes insipidus due to hydrocephalus, though rare, can have serious complications including the predilection to develop a deficit of other pituitary hormones. Thus, even if hydrocephalus is dormant with normal intracranial pressure, it must be addressed during investigations of central diabetes insipidus.

BackgroundEmerging data suggest that sodium disarrays including hyponatremia are potential risk factors for infection ensuing from impairments in host immunity, which may be exacerbated by coexisting conditions (i.e. mucosal membrane and cellular edema leading to breakdown of microbial barrier function). While dysnatremia and infection-related mortality are common in dialysis patients, little is known about the association between serum sodium levels and the risk of bloodstream infection in this population.MethodsAmong 823 dialysis patients from the national Biospecimen Registry Grant Program who underwent serum sodium testing over the period January 2008-December 2014, we examined the relationship between baseline serum sodium levels and subsequent rate of bloodstream infection. Bloodstream infection events were directly ascertained using laboratory blood culture data. Associations between serum sodium level and the incidence of bloodstream infection were estimated using expanded case mix-adjusted Poisson regression models.ResultsIn the overall cohort, ∼10% of all patients experienced one or more bloodstream infection events during the follow-up period. Patients with both lower sodium levels

Background: Diabetes insipidus is a syndrome characterized by polyuria, which is almost always associated with polydipsia. The most frequent cause is central diabetes insipidus, which is the result of an inadequate secretion of the antidiuretic hormone, and diagnosis involves differentiating it from other causes of polyuria and polydipsia. Case presentation: Here, we present a clinical case of a previously healthy 13-year-old Nepali boy, who, in December 2022, was found to have intense polydipsia accompanied by polyuria. He had bilateral lower limb weakness at the time of presentation. Biochemical evaluation demonstrated raised serum sodium (181 mEq/L), serum creatinine (78 μmol/L), and serum uric acid (560 μmol/L) with suppressed serum potassium (2.7 mEq/L), which was the major concern to the clinicians. Further laboratory workup revealed an increased serum osmolarity (393.6 mOsm/kg) with reduced urine osmolarity (222.7 mOsm/kg). On contrast magnetic resonance imaging of the brain, a thick-walled third ventricular cyst with bilateral foramen obstruction, thin membrane-like structure at top of aqueduct of Sylvius with gross obstructive hydrocephalus (inactive), and compressed and thinned pituitary gland with no bright spot was observed. The laboratory findings, radiological findings, and case presentation provided the provisional diagnosis of diabetes insipidus due to hydrocephalus and third ventricular cyst. Conclusions: Central diabetes insipidus due to hydrocephalus, though rare, can have serious complications including the predilection to develop a deficit of other pituitary hormones. Thus, even if hydrocephalus is dormant with normal intracranial pressure, it must be addressed during investigations of central diabetes insipidus. [ABSTRACT FROM AUTHOR]

In this segment of the emergency department (ED) palliative care case series, we present a patient who arrives to the ED after a fall resulting in a hip fracture. He is also found to have hypernatremia and an acute kidney injury and develops delirium while in the ED awaiting an inpatient bed. The ED-based integrated geriatric palliative care program is consulted and performs a multidimensional assessment. The geriatric palliative care clinician facilitates discussion with his daughter about surgical intervention based on the patient's goals and values, diagnoses delirium, and worsening depression, creates a plan for delirium and pain management, and accelerates postdischarge planning. [ABSTRACT FROM AUTHOR]

Although protein reabsorption in the renal proximal tubules is concurrent with ion and water transport, little is known about the dependence of receptor-mediated protein endocytosis on changes in water and salt balance. The aim of the study was to investigate tubular reabsorption and intracellular vesicular transport of various proteins in a lake frog (Pelophylax ridibundus) model of hypernatremia. The frogs were injected with hypertonic sodium chloride solution (0.75 M NaCl) 1 h before the administration of green or yellow fluorescent proteins (GFP or YFP), as well as lysozyme. Fluorescent immunohistochemistry and confocal microscopy were used to detect lysozyme and the endocytic receptor megalin in the epithelial cells of proximal tubules. The endocytosis dynamics was assessed by automated quantification of colocalized fluorescent signals of megalin and injected proteins. We found a statistically significant decrease in the reabsorption of GFP, YFP, and lysozyme in proximal tubules after NaCl injection. The accumulation of proteins in early endosomes and the decrease in their entry into late endosomes and lysosomes suggest a delay in the intracellular vesicular transport of proteins under hypernatremia. The data obtained are analyzed as related to changes in blood parameters and kidney activity during osmoregulation, as well as to the role of chloride channels in receptor-mediated protein endocytosis. We assume that increased ion transport in proximal tubular epitheliocytes under hypernatremia conditions leads to a decreased protein reabsorption capacity of these cells and delayed intracellular transport of proteins. [ABSTRACT FROM AUTHOR]

Background: Craniopharyngiomas are low‐grade malignancies (WHO I) in the sellar region. Most cases of childhood‐onset craniopharyngioma are adamantinomatous craniopharyngioma, and neurosurgery is the treatment of choice. Affected patients have postoperative complications, including water and electrolyte disturbances, because these malignancies develop near the hypothalamus and pituitary gland. Determining postoperative serum sodium fluctuation patterns in these patients can reduce postoperative mortality and improve prognosis. Objective: To measure changes in serum sodium levels in pediatric patients who underwent craniopharyngioma surgery and identify influencing factors. Methods: This retrospective study measured the serum sodium levels of 202 patients aged 0–18 years who underwent craniopharyngioma resection in Beijing Tiantan Hospital and Beijing Children's Hospital and identified predictors of severe hyponatremia and hypernatremia. Results: The mean age of the cohort was 8.35 ± 4.35 years. The prevalence of hypernatremia, hyponatremia, and their severe forms (serum Na+ > 150 mmol/L and serum Na+ < 130 mmol/L) within 14 days after surgery was 66.3%, 72.8%, 37.1%, and 40.6%, respectively. The mean postoperative serum sodium level showed a triphasic pattern, characterized by two peaks separated by a nadir. Sodium levels peaked on days 2 (143.6 ± 7.6 mmol/L) and 14 (143.2 ± 6.7 mmol/L) and reached their lowest on day 6 (135.5 ± 7.5 mmol/L). A total of 31 (15.3%) patients met the diagnostic threshold for hyponatremia and hypernatremia of the triphase response, whereas 116 (57.4%) patients presented this pattern, regardless of met the diagnostic criteria or not. The prevalence of severe hyponatremia varied depending on preoperative endocrine hormone deficiency, tumor status (primary or recurrent), and surgical approach. Conclusions: Serum sodium levels after craniopharyngioma resection in children showed a triphasic pattern in most cases. The risk of postoperative hyponatremia varied depending on preoperative endocrine hormone deficiency, tumor status (primary or recurrent), and surgical approach. [ABSTRACT FROM AUTHOR]

Background/Aim: The current study was designed to evaluate the etiologies of hypernatremic episodes in patients with severe burn injuries in comparison to critically ill non-burn patients. Patients and Methods: The retrospective data acquisition was limited to the first 14 days and to patients with at least 20% total body surface area (TBSA) 2nd degree burn injuries or more than 10% TBSA when including areas of 3rd degree burn injuries. The results were compared to the results of a previously published study that analyzed the risk factors for hypernatremia in 390 nonburn intensive care unit patients. Results: In total, 120 patients with a total of 50 hypernatremic episodes were included. Compared to non-burn injury patients, no significant differences were detectable except for a lower rate of hypokalemia and a higher rate of mechanical ventilation. The main trigger for hypernatremic episodes was the loss of free water, while 24% of the hypernatremic episodes seemed to be at least partly triggered by a surplus sodium influx. Patients with hypernatremic episodes had a significantly higher mortality rate. However, in none of the cases was hypernatremia the decisive cause of death. Conclusion: Besides the unique phenomenon of high volume internal and external volume shifts, the overall risk factors and etiologies of hypernatremia in patients with severe burn injury do not seem to significantly differ from other ICU patient collectives. Remarkably, a surplus of sodium influx and therefore a modifiable factor besides the specific burn injury volume resuscitation had an impact on the hypernatremic episodes in 24% of cases. [ABSTRACT FROM AUTHOR]