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Background: To date, inconsistent evidence exists on the role of hypernatremia in patients with aneurysmal subarachnoid hemorrhage (aSAH) who underwent surgical clipping. We aimed to investigate the association between serum sodium and mortality in these patients., Methods: A cohort study was performed to include adult patients with aSAH who underwent surgical clipping in a university hospital. The primary outcome was follow-up mortality. Propensity score matching (PSM) was used for matching patients' baseline characteristics. Net reclassification improvement (NRI), and integrated discrimination improvement (IDI) were calculated to assess and compare the reclassification and discrimination capacity of different models. Trends in serum sodium over time were detected by the ordinary least squares model., Results: Of 618 aSAH patients with surgical clipping during the study period, normal serum sodium was observed in 467 patients (75.6 %), and admission hypernatremia was noted in 151 patients (24.4 %). After adjustment with multivariate regression analysis, patients with hypernatremia had significantly higher odds for follow-up mortality (aOR: 2.86, 95 % CI: 1.54 to 5.30; P = 0.001). PSM analysis observed similar results (aOR: 2.38, 95 % CI: 1.29 to 4.55; P = 0.009). The incorporation of serum sodium during hospitalization markedly enhanced the IDI (P < 0.001) and NRI (P < 0.001) for the prediction of mortality., Conclusions: In conclusion, the findings from this cohort study of aSAH patients with surgical clipping indicated that serum sodium can be an independent predictive factor of all-cause mortality, and inferior sequelae in aSAH patients. These findings endorsed the importance of managing hypernatremia and monitoring serum sodium in patients with aSAH., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Previous studies have shown that hyponatremia was strongly associated with a poor prognosis of type 1 pulmonary hypertension, and our team's antecedent studies found that low serum sodium was associated with the severity and the length of hospitalization of pulmonary hypertension associated with left ventricular disease (PH-LHD). However, the relationship between serum sodium and the prognosis of PH-LHD remains unclear. This study aims to determine the clinical value of serum sodium in evaluating poor prognosis in patients with PH-LHD., Methods: We successfully followed 716 patients with PH-LHD. Kaplan-Meier was used to plot survival in PH-LHD patients with different serum sodium levels. The effect of serum sodium on poor prognosis was analyzed using a Cox proportional risk model. The trends between patients serum sodium and survival were visualized by restricted cubic spline (RCS)., Results: The survival rates at 1, 2, 3 and 4 years were 52%, 41%, 31% and 31% for the patients with hyponatremia associated with PH-LHD and 71%, 71%, 71% and 54% for the patients with hypernatremia, respectively. The observed mortality rate in the hyponatremia and hypernatremia groups surpassed that of the normonatremic group. The adjusted risks of death (risk ratio) for patients with hyponatremia and hypernatremia were found to be 2.044 and 1.877. Furthermore, the restricted cubic spline demonstrated an L-shaped correlation between serum sodium and all-cause mortality in patients with PH-LHD., Conclusions: Abnormal serum sodium level is strongly associated with poor prognosis in PH-LHD. Serum sodium may play an important pathogenic role in PH-LHD occurrence and could be used as a marker to assess the survival in patients., Competing Interests: Declaration of competing interest The author reports no conflicts of interest in this work., (Copyright © 2024 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.)

Hyponatremia is the most common electrolyte abnormality encountered in critically ill patients and is linked to heightened morbidity, mortality, and healthcare resource utilization. However, its causal role in these poor outcomes and the impact of treatment remain unclear. Plasma sodium is the main determinant of plasma tonicity; consequently, hyponatremia commonly indicates hypotonicity but can also occur in conjunction with isotonicity and hypertonicity. Plasma sodium is a function of total body exchangeable sodium and potassium and total body water. Hypotonic hyponatremia arises when total body water is proportionally greater than the sum of total body exchangeable cations, that is, electrolyte-free water excess; the latter is the result of increased intake or decreased (kidney) excretion. Hypotonic hyponatremia leads to water movement into brain cells resulting in cerebral edema. Brain cells adapt by eliminating solutes, a process that is largely completed by 48 h. Clinical manifestations of hyponatremia depend on its biochemical severity and duration. Symptoms of hyponatremia are more pronounced with acute hyponatremia where brain adaptation is incomplete while they are less prominent in chronic hyponatremia. The authors recommend a physiological approach to determine if hyponatremia is hypotonic, if it is mediated by arginine vasopressin, and if arginine vasopressin secretion is physiologically appropriate. The treatment of hyponatremia depends on the presence and severity of symptoms. Brain herniation is a concern when severe symptoms are present, and current guidelines recommend immediate treatment with hypertonic saline. In the absence of significant symptoms, the concern is neurologic sequelae resulting from rapid correction of hyponatremia which is usually the result of a large water diuresis. Some studies have found desmopressin useful to effectively curtail the water diuresis responsible for rapid correction., Competing Interests: Declaration of Conflicting InterestsThe author declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

A 72-year-old female experienced severe hyponatremia, leading to a serum sodium level of 102.5 mEq/L. Sodium levels were rapidly increased, resulting in osmotic demyelination syndrome (ODS). Magnetic resonance imaging is the most appropriate diagnostic tool for ODS, with the classic trident-shaped appearance formed by the hyperintense central pontine signal. Patients with ODS often require intensive supportive care and relowering of sodium levels., (© Journal of the Association of Physicians of India 2024.)

Background and Objective: Hypernatremia is a possible side effect of intravenous fosfomycin. The aim of this study was to investigate the effects of changes in sodium (Na) levels on hospital stay and survival in patients hospitalized in the intensive care unit receiving fosfomycin., Subjects and Methods: This study was conducted retrospectively on the files of patients over the age of 60, who were admitted to the Internal Medicine Intensive Care Unit. Plasma sodium levels were observed and documented over a period of 14 days. The patients were divided into two groups (Hypernatremia group Na > 145 mEq/L vs normonatremia group 135-145 mEq/L). In addition, daily sodium changes were noted for 14 days in patients., Results: The mean age of the patients was 75 years. Hospitalization days were longer for hypernatremia patients (31.5 days vs 41 days, p = 0.003). Patients with hypernatremia had an extended duration of stay in the intensive care unit. (21 days vs 31 days p = 0.002). The 1-month survival rate was 61.4% in patients with hypernatremia and 24.9% in patients without hypernatremia (p = 0.004). The absence of hypernatremia increases mortality by 2.09 times (95% CI 1.35-3.23). When discharge and mortality rates were analyzed according to sodium fluctuation, discharged patients exhibited a lower sodium fluctuation (4 min/max (-10/19) vs 6 min/max (-16/32) p < 0.001)., Conclusion: In conclusion, the strength of our study is that it specifically focuses on the consequences of the sodium fluctuation on patient management and provides results., (© 2024. The Author(s), under exclusive licence to Royal Academy of Medicine in Ireland.)

Objective: To evaluate the association between enteral sodium supplementation on growth and hypertension (HTN) in preterm infants., Study Design: A retrospective cohort study of infants born between 22-32 weeks and weighing 450-1500 grams (N = 821). Enteral sodium supplementation amounts, systolic blood pressures (SBP), weight gain, and other infant and maternal risk factors for HTN were electronically extracted., Results: Infants receiving sodium supplementation were smaller and less mature. Sodium supplementation improved serum sodium levels, weight gain, and head circumference growth without causing hypernatremia. There was no correlation between urine and serum sodium or urine sodium and weight gain. Although infants receiving sodium had higher average SBP and rates of HTN, analysis demonstrated sodium supplementation did not increase odds of hypertension (OR ADJ 1.02;0.64-1.64). Postnatal steroids were associated with HTN., Conclusions: In preterm infants with poor weight gain, enteral sodium supplementation improved growth without increasing hypertension or hypernatremia., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Human red blood cells (RBCs) undergo ionic leakage through passive diffusion during refrigerated storage, affecting their quality and health. We investigated the dynamics of ionic leakage in human RBCs over a 20-day refrigerated storage period using extracellular ion quantification and dielectrophoresis (DEP). Four type O- human blood donors were examined to assess the relationship between extracellular ion concentrations (Na + , K + , Mg 2+ , Ca 2+ , and Fe 2+ ), RBC cytoplasm conductivity, and membrane conductance. A consistent negative correlation between RBC cytoplasm conductivity and membrane conductance, termed the "ionic leakage profile" (ILP), was observed across the 20-day storage period. Specifically, we noted a gradual decline in DEP-measured RBC cytoplasm conductivity alongside an increase in membrane conductance. Further examination of the electrical origins of this ILP using inductively coupled plasma mass spectrometry revealed a relative decrease in extracellular Na + concentration and an increase in K + concentration over the storage period. Correlation of these extracellular ion concentrations with DEP-measured RBC electrical properties demonstrated a direct link between changes in the cytoplasmic and membrane domains and the leakage and transport of K + and Na + ions across the cell membrane. Our analysis suggests that the inverse correlation between RBC cytoplasm and membrane conductance is primarily driven by the passive diffusion of K + from the cytoplasm and the concurrent diffusion of Na + from the extracellular buffer into the membrane, resulting in a conductive reduction in the cytoplasmic domain and a subsequent increase in the membrane. The ILP's consistent negative trend across all donors suggests that it could serve as a metric for quantifying blood bank storage age, predicting the quality and health of refrigerated RBCs., (© 2024 The Author(s). ELECTROPHORESIS published by Wiley‐VCH GmbH.)

Introduction: The 2021 American Association for the Study of Liver Disease (AASLD) Practice Guidance recommends albumin infusion when removing ≥5 L of ascites to prevent post-paracentesis circulatory dysfunction. However, the optimal criteria and scenarios for initiating albumin infusion subsequent to therapeutic paracentesis (TP) have been subject to limited scientific inquiry., Methods: We conducted a retrospective cohort study at a US academic healthcare center. Participants received elective, outpatient TP between July 2019 and December 2022. Patients with spontaneous bacterial peritonitis, post-TP clinical adjustments, and/or hospitalization were excluded. The institution strictly followed the AASLD Guidance. We used a sharp regression discontinuity (RD) design to estimate the effect of albumin infusion at the AASLD Guidance-recommended cutoff of 5 L on serum creatinine and sodium trajectory after TP., Results: Over the study period, 1,457 elective TPs were performed on 235 unique patients. Albumin infusion at the threshold of 5 L of ascites removal reduced serum creatinine levels by 0.046 mg/dL/d (95% confidence interval 0.003-0.116, P = 0.037) and increased serum sodium levels by 0.35 mEq/L/d (95% confidence interval 0.15-0.55, P = 0.001) compared with those who did not receive albumin infusion. The RD plots indicated worsened serum creatine/sodium levels after draining 3 L of fluid, approaching levels similar to or worse than with albumin infusion at 5 L or more., Discussion: Our RD models supported the 2021 AASLD Guidance with robust estimation of causal effect sizes at the cutoff level of 5 L. Nevertheless, the findings also highlight the need to further evaluate the efficacy of albumin infusion in patients who undergo elective TP and have 3-5 L of ascites removed., (Copyright © 2024 by The American College of Gastroenterology.)

Sodium serves as one of the primary cations in the central nervous system, playing a crucial role in maintaining normal brain function. In this study, we investigated alterations in sodium concentrations in the brain and/or cerebrospinal fluid across multiple models, including an aging model, a stroke model, a nitroglycerin (NTG)-induced rat migraine model, a familial hemiplegic migraine type 2 (FHM2) mouse model, and a transgenic mouse model of Alzheimer's disease (AD). Our results reveal that older rats exhibited higher sodium concentrations in cerebrospinal fluid (CSF), plasma, and various brain regions compared to their younger counterparts. Additionally, findings from the stroke model demonstrated a significant increase in sodium in the ischemic/reperfused region, accompanied by a decrease in potassium and an elevated sodium/potassium ratio. However, we did not detect significant changes in sodium in the NTG-induced rat migraine model or the FHM2 mouse model. Furthermore, AD transgenic mice showed no significant differences in sodium levels compared to wild-type mice in CSF, plasma, or the hippocampus. These results underscore the nuanced regulation of sodium homeostasis in various neurological conditions and aging, providing valuable insights into potential mechanisms underlying these alterations., (© 2024. The Author(s).)

Context: Thiazide-induced hyponatremia is one of the most common forms of hyponatremia, but its pathogenesis is incompletely understood. Recent clinical data suggest links with prostaglandin E2 (PGE2) and a single nucleotide polymorphism (SNP) in the prostaglandin transporter gene (SLCO2A1), but it is unknown if these findings also apply to the general population., Objective: To study the associations between serum sodium, thiazide diuretics, urinary excretions of PGE2, and its metabolite (PGEM), and the rs34550074 SNP in SLCO2A1 in the general population., Design: Prospective population-based cohort study (Rotterdam Study)., Setting: General population., Participants: 2178 participants (65% female, age 64 ± 8 years)., Intervention(s): None., Main Outcome Measure(s): Serum sodium levels., Results: Higher urinary PGE2 excretion was associated with lower serum sodium: difference in serum sodium for each 2-fold higher PGE2 -0.19 mmol/L [95% confidence interval (CI) -0.31 to -0.06], PGEM -0.29 mmol/L (95% CI -0.41 to -0.17). This association was stronger in thiazide users (per 2-fold higher PGE2 -0.73 vs -0.12 mmol/L and PGEM -0.6 vs -0.25 mmol/L, P for interaction <.05 for both). A propensity score matching analysis of thiazide vs non-thiazide users yielded similar results. The SNP rs34550074 was not associated with lower serum sodium or higher urinary PGE2 or PGEM excretion in thiazide or non-thiazide users., Conclusion: Serum sodium is lower in people with higher urinary PGE2 and PGEM excretion, and this association is stronger in thiazide users. This suggests that PGE2-mediated water reabsorption regulates serum sodium, which is relevant for the pathogenesis of hyponatremia in general and thiazide-induced hyponatremia specifically., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society.)

Background and Objectives: Emerging research suggests that hyperammonemia may enhance the probability of hepatic encephalopathy (HE), a condition associated with elevated levels of circulating ammonia in patients with cirrhosis. However, some studies indicate that blood ammonia levels may not consistently correlate with the severity of HE, highlighting the complex pathophysiology of this condition., Methods: A systematic review and meta-analysis through PubMed, Scopus, Embase, Web of Science, and Virtual Health Library were conducted to address this complexity, analyzing and comparing published data on various laboratory parameters, including circulating ammonia, blood creatinine, albumin, sodium, and inflammation markers in cirrhotic patients, both with and without HE., Results: This comprehensive review, which included 81 studies from five reputable databases until June 2024, revealed a significant increase in circulating ammonia levels in cirrhotic patients with HE, particularly those with overt HE. Notably, significant alterations were observed in the circulating creatinine, albumin, sodium, interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNFα) in HE patients., Conclusions: These findings suggest an association between ammonia and HE and underscore the importance of considering other blood parameters such as creatinine, albumin, sodium, and pro-inflammatory cytokines when devising new treatment strategies for HE., Competing Interests: The authors have declared that no competing interests exist, (Copyright: © 2024 Sepehrinezhad et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Hyponatremia is a common electrolyte disturbance among hospitalized patients and is linked to increased mortality as well as poor outcomes., Objectives: Study the prevalence of hyponatremia among medically admitted patients and the outcomes associated with hyponatremia., Design: Retrospective cohort., Setting: Medical ward at tertiary hospital setting., Patients and Methods: The study included adult (≥18 years) hospitalized patients in general medical wards. Three readings of serum sodium level were taken (initial sodium level, nadir during admission, and before discharge)., Sample Size and Basis: The sample size of 350 was determined based on a presumed 35% incidence of hyponatremia among hospitalized patients, with a 5% error margin., Main Outcome Measures: The prevalence of hyponatremia among medically hospitalized patients and association with health outcomes including length of hospital stay, inpatient mortality, 90-days readmission and 1-year mortality., Results: In this study, 736 patients met the inclusion criteria. Of these, 377 (51.2%) had hyponatremia on admission, increasing to 562 (76.35%) during hospitalization. Mild hyponatremia was observed in 49.6% (n=365), moderate in 13.6% (n=100), and severe in 13.2% (n=97). Severe hyponatremia patients were significantly older ( P <.01), predominantly female ( P =.014), and had lower serum magnesium and albumin levels ( P <.01). Hypertension, ischemic heart disease, heart failure, and diabetes were more prevalent in severe hyponatremia cases ( P <.01, P <.01, P =.045, P <.01, respectively). Hospital stays were significantly shorter for patients with normal sodium levels ( P <.01). Patients with severe hyponatremia had a shorter time for first hospital readmission (HR=0.80, P <.01 [95% CI; 0.69-0.94])., Conclusion: Hyponatremia was prevalent among medically hospitalized patients and more common among old patients, women, and patients with comorbidities. Hyponatremia was associated with increased length of stay in hospital and increased risk of 90-day re-admission., Limitations: Single-centre design and retrospective nature.

Introduction: Serum sodium levels <135 mmol/L are known as hyponatremia. The syndrome of inappropriate antidiuresis (SIAD), which is described by a drop in the effective arterial blood volume (EABV), is the most common cause of hyponatremia. This study was carried out to categorize hyponatremia based on volume status and on parameters like fractional excretion of uric acid (FE-UA), fractional excretion of sodium (FE-Na), urine uric acid (U-UA), and serum uric acid (SR-UA) values., Materials and Methods: Sixty-one patients admitted to the Department of Medicine at Rajendra Institute of Medical Sciences (RIMS), Ranchi, with hyponatremia were included in the study by applying random sampling. Routine urine and blood samples were collected for biochemical tests. Institutional ethical clearance was obtained for this study. Data were analyzed using Statistical Package for the Social Sciences (SPSS) (version 21). Frequency, central tendency, receiver operating characteristic (ROC), and nonparametric Mann-Whitney U test analysis tools were utilized for analysis., Results: Syndrome of inappropriate antidiuretic hormone secretion (SIADH) was found in nearly 50.82% of hyponatremic patients. Approximately, 70% of non-SIADH patients were hypovolemic. When compared to the non-SIADH group, patients in the SIADH group had significantly higher systolic blood pressure (SBP) and diastolic blood pressure (DBP), lower pulse rates, and lower urine creatinine levels and urine creatinine to serum creatinine ratio. The non-SIADH group had significantly higher SR-UA levels ( p < 0.0001), but the SIADH group had significantly higher U-UA levels and significantly lower SR-UA levels. Among the studied parameters, FE-UA was the most accurate in diagnosing SIADH. FE-UA (>12%) is a better diagnostic marker for distinguishing SIADH patients from non-SIADH patients., Conclusion: FE-uric acid was found to be the most superior in diagnosing SIADH, followed by FE-Na., (© Journal of the Association of Physicians of India 2024.)

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., (© 2024. The Author(s).)

Background & Aims: Athletes are commonly exposed to exercise-induced dehydration. However, the best method to detect dehydration under this circumstance is not clear. This study aimed to analyze pre- and post-dehydration measurements of biomarkers, including saliva osmolality (SOsm), urine osmolality (UOsm), urine-specific gravity (USG), urine color (Ucolor), serum osmolality (SeOsm), serum arginine vasopressin (AVP), serum sodium (Na + ), and thirst sensation in underhydrated athletes, using the body mass loss (BML) as the reference method., Methods: In this clinical trial (NCT05380089), a total of 38 athletes (17 females) with a regular low water intake (<35 mL/kg/day) were submitted to exercise-induced dehydration with a heat index of 29.8 ± 3.1 °C and an individualized running intensity (80-90% of first ventilatory threshold)., Results: ROC curve analysis revealed significant discriminative abilities of SOsm, with AUC values of 0.76 at 1.5% BML, 0.75 at 1.75% BML, and 0.87 at 2% BML, while Na + and SeOsm showed the highest AUC of 0.87 and 0.91 at 2% BML, respectively. SOsm showed high sensitivity at 1.5% of BML, while SeOsm and Na + demonstrated high sensitivity at 2% of BML., Conclusion: This study highlights SOsm as a potential indicator of hydration status across different levels of BML. Additionally, Na + and SeOsm emerged as accurate dehydration predictors at 1.75% and 2% of BML. Notably, the accuracy of urinary indices and thirst sensation for detecting hydration may be limited., Competing Interests: Conflict of interest The authors declare no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Introduction: Hyponatremia is a well-documented adverse effect of oxcarbazepine treatment, but no clinical trial has yet been conducted to explore any intervention for reducing the incidence of hyponatremia., Materials and Methods: This open-label trial evaluated the efficacy of add-on daily oral sodium chloride supplementation of 1-2 g/day for 12 weeks in reducing the incidence of hyponatremia in children receiving oxcarbazepine monotherapy aged 1-18 years. Apart from comparing the incidence of symptomatic and severe hyponatremia, serum and urine sodium levels, serum and urine osmolality, changes in behavior and cognition, and the number of participants with recurrence of seizures and requiring additional antiseizure medication (ASM) were also compared., Results: A total of 120 children (60 in each group) were enrolled. The serum sodium level at 12 weeks in the intervention group was higher than that of the control group (136.5 ± 2.6 vs 135.4 ± 2.5 mEq/L, p = 0.01). The number of patients with hyponatremia was significantly lower in the intervention group (4/60vs14/60, p = 0.01). However, the incidence of symptomatic and severe hyponatremia (0/60vs1/60, p = 0.67 for both), changes in social quotient and child behavior checklist total score (0.6 ± 0.8 vs 0.7 ± 0.5, p = 0.41 and 0.9 ± 1.2 vs 1.1 ± 0.9, p = 0.30 respectively), the number of patients with breakthrough seizures (9/60vs10/60, p = 0.89), and the number of patients requiring additional ASMs (8/60vs10/60, p = 0.79) were comparable in both groups., Conclusions: Daily oral sodium chloride supplementation is safe and efficacious in reducing the incidence of hyponatremia in children with epilepsy receiving oxcarbazepine monotherapy. However, sodium chloride supplementation does not significantly reduce more clinically meaningful outcome measures like symptomatic and severe hyponatremia. Trial registry No. CTRI/2021/12/038388., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Introduction: Hypernatremia is a common problem among patients with severe burn injuries and seems to be associated with an unfavorable clinical outcome. The current study was designed to evaluate the impact of antibiotics with a high proportion of sodium on this phenomenon., Methods: All admissions to our burn center from 01/2017 till 06/2023 were retrospectively screened. All patients aged >18 years which suffered from at least 20 % total body surface burned area (TBSA) 2nd degree burn injuries or more than 10 % TBSA when including areas of 3rd degree burn injuries were included. The course of the serum Na-level was analyzed from two days before till two days after the start of the antibiotic treatment. Ampicillin/sulbactam, cefazoline and piperacillin/tazobactam were classified as high-dose sodium antibiotics (HPS), meropenem and vancomycin as low-dose sodium antibiotics (LPS)., Results: 120 patients met the inclusion criteria. A significant increase of the serum Na was detectable in the HPS group on day 1 and 2 after initiating the antibiotic treatment (n = 64, day 1: 2,1 (SD 4,18) mmol/l, p < 0,001; day 2: 2,44 (SD 5,26) mmol/l, p < 0,001) while no significant changes were detectable in the LPS group (n = 21, day 1: 0,18 (SD 7,45) mmol/l, p = 0,91; day 2: -0,27 (SD 7,44) mmol/l, p = 0,87). This effect was further aggravated when analyzing only the HPS patients with a TBSA ≥30 % (n = 33; day 1: 2,93 (SD 4,68) mmol/l, p = 0,002; day 2: 3,41 (SD 5,9) mmol/l, p = 0,003)., Conclusion: The amount of sodium in antibiotics seems to have a relevant impact on the serum Na during the early stages of severe burn injury. Therefore, this aspect should be taken into account when searching for the most appropriate antibiotic treatment for patients with severe burn injury, especially when being at acute risk for a clinical relevant hypernatremia., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Whether blood laboratory analyses differ in patients who later suffer in-hospital cardiac arrest (IHCA) compared to other hospitalised patients remains unknown. The aim of this study was to describe pre-arrest sampling frequencies, results, and trends in blood laboratory analyses in patients with IHCA compared to controls., Methods: This study was a matched case-control study using national registries in Denmark. Cases were defined as patients with IHCA from 2017 to 2021. Controls were defined as hospitalised patients and were matched on age, sex, and date and length of admission. Data on a total of 51 different blood laboratory analyses were obtained. The laboratory analyses of primary interest were lactate, sodium, potassium, and haemoglobin. The index time for cases was defined as the time of cardiac arrest, and a corresponding index time was defined for controls based on the time to cardiac arrest for their corresponding case. Blood sampling frequencies were reported for blood laboratory analyses obtained either within the last 24 h before the index time or between the time of hospital admission and the index time. Blood sampling results were reported for blood laboratory analyses obtained within the last 24 h before the index time., Results: A total of 9268 cases and 92,395 controls were included in this study. Cases underwent more frequent sampling of all blood laboratory analyses compared to controls. This higher sampling frequency was more pronounced for lactate compared to sodium, potassium, or haemoglobin. The last measured lactate was higher in cases (median [IQR]: 2.3 [1.3, 4.9]) compared to controls (median [IQR]: 1.3 [0.9, 2.0]). Differences in sodium, potassium, and haemoglobin were negligible. The proportion of abnormally elevated levels of lactate and potassium increased as time to cardiac arrest decreased; no such effect was seen in controls. No temporal trend was evident for sodium or haemoglobin., Conclusions: Patients with IHCA undergo more frequent blood sampling prior to IHCA and have higher levels of lactate compared to matched controls., (© 2024 The Author(s). Acta Anaesthesiologica Scandinavica published by John Wiley & Sons Ltd on behalf of Acta Anaesthesiologica Scandinavica Foundation.)

Background: Disorders of serum sodium are common among general patients and are associated with poor outcomes. The prognostic value of serum sodium disorders in patients with acute pancreatitis (AP) has not been studied. We conducted this retrospective study to explore the association between serum sodium levels and the outcomes of patients with AP., Materials and Methods: Patients with AP from the Medical Information Mart for Intensive Care III (MIMIC-III) were screened for this study. The laboratory variables, including serum sodium levels, were obtained by analyzing the first blood sample on the first day after admission. Univariate logistic regression was performed to discover potential factors for mortality of AP. The unadjusted and adjusted association between serum sodium level and mortality of AP was shown by the restricted cubic spline (RCS). The categorical cutoff for the detrimental effect of serum sodium level on the prognosis of AP was also confirmed by stepwise logistic regression after adjusting for con-founding effects of significant factors in the univariate logistic regression., Results: A total of 869 patients with AP in the MIMIC-III were included with a mortality of 13.1%. Unadjusted logistic regression showed that age (p < 0.001), simplified acute physiological score (SAPS) (p < 0.001), systolic blood pressure (p < 0.001), diastolic blood pressure (p < 0.001), hemoglobin (p = 0.040), serum creatinine (p = 0.046), and serum phosphorus (p < 0.001) were significantly associated with the mortality of AP. The RCS showed that the serum sodium level was negatively and linearly associated with mortality of AP after adjusting for confounding effects of significant factors in the univariate logistic regression. Serum sodium < 133 mmol/L, which indicated hyponatremia, was significantly correlated with a higher mortality risk than serum sodium ≥ 133 mmol/L (p = 0.013)., Conclusions: Hyponatremia is widely developed among patients with AP and correlates with a higher mortality risk of AP. Physicians should pay more attention to managing patients with AP with hyponatremia., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction: Disturbances in plasma sodium levels are a major complication following recent resections of craniopharyngiomas in children. They must be properly managed to avoid neurological sequelae. We aimed to describe the variations and characteristics of postoperative natremia in children who had undergone a first craniopharyngioma resection with a particular focus on the frequency of triphasic syndrome in these patients., Methods: Paediatric patients with craniopharyngiomas who underwent a first surgical resection in the neurosurgery department of the Hôpital Femme Mère Enfant (Lyon, France) between January 2010 and September 2021 were included in the present study and the medical records were analysed retrospectively., Results: A total of 26 patients were included. Of these, 17 (65.4%) had a postoperative course characterised by the occurrence of both initial diabetes insipidus (DI) and hyponatremia a few days later. Eight patients (30.8%) presented then with isolated and persistent DI. Patients with the triphasic syndrome had a significantly higher grade of Puget classification on MRI (1 and 2), compared to the other patients., Conclusion: Dysnatremia is common after craniopharyngioma resections in children. This immediate postoperative complication is particularly difficult to manage and requires rapid diagnosis and prompt initiation of medical treatment to minimize fluctuations in sodium levels and avoid neurological sequelae., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Hyponatremia, a prevalent electrolyte imbalance among tumor patients, has often been overlooked regarding its prognostic significance for immunotherapy. In this study, we delved into the prognostic ramifications of hyponatremia in advanced gastric cancer (AGC) patients undergoing immunotherapy. Enrolling AGC patients diagnosed between December 2014 and May 2021, we extracted pertinent data from electronic medical records, with a median follow-up of 35.8 months. Kaplan-Meier curves illuminated patients' progression-free survival (PFS) and overall survival (OS), while survival disparities were tested using the Mantel-Haenszel log rank test. COX and logistic regressions were employed to scrutinize the correlation between serum sodium levels and prognosis in 268 AGC patients, both at baseline and during treatment. Notably, patients with hyponatremia exhibited shorter PFS (4.7 vs 2.1 months, p = .001*) and OS (12.5 vs 3.9 months, p  < .001*). Serum sodium emerged as an independent prognostic factor for both PFS (HR = 1.773; 95% CI 1.067-2.945; p  = .001*) and OS (HR = 1.773; 95% CI 1.067-2.945; p = .003*). Subgroup analysis revealed that AGC patients with hyponatremia derived no benefit from immunotherapy in terms of PFS and OS. Strikingly, a decrease in serum sodium during immunotherapy was associated with early relapse and mortality. Based on these findings, we hypothesize that hyponatremia portends poor prognostic outcomes in AGC patients treated with immunotherapy and may serve as a valuable prognostic biomarker. However, further large-scale prospective studies are warranted to validate these observations.

Background: Chloride has prognostic implications in heart failure (HF). The sodium:chloride (Na:Cl) ratio gathers information of both ions., Objectives: To study the prognostic impact of Na:Cl ratio in acute HF., Methods: We retrospectively analysed patients included in an acute HF cohort in 2009-2010., Primary Endpoint: all-cause mortality., Follow-Up: 1-year from admission to study the impact of admission Na:Cl ratio; 1-year post-discharge to study the discharge ratio impact. ROC curves of the association of Na, Cl, and the Na:Cl ratio with 1-year mortality were determined and the AUC compared. The association of Na:Cl ratio with mortality was assessed in multivariate analyses., Results: We studied 616 patients. Median admission Na:Cl ratio = 1.34 (1.31-1.38). During 1-year since admission, 229 patients died, AUC for death-association of admission Na, Cl and Na:Cl ratio = 0.42 (0.38-0.47), 0.39 (0.35-0.44) and 0.58 (0.53-0.63), respectively, with significant difference between Na:Cl ratio curve and the others. When admission Na:Cl ratio ≥ 1.34, the multivariate-adjusted death-risk was 1.41 (1.04-1.89); 1.32 (1.04-1.68), per each 0.1 increase in ratio. In-hospital death rate was 4.1 %, median discharge Na:Cl ratio = 1.40 (1.37-1.45). During 1-year post-discharge, 205 patients (34.9 %) died; AUC for Na, Cl and Na:Cl ratio: 0.45 (0.40-0.50), 0.41 (0.36-0.46) and 0.57 (0.52-0.62), with differences between Na:Cl ratio curve and the others. When discharge Na:Cl ratio ≥ 1.43 (percentile 66.7), the adjusted-HR of death was 1.43 (1.04-1.97), p = 0.03, 1.54 (1.23-1.92) per 0.1 increase., Conclusions: Elevated Na:Cl ratio is independently associated with all-cause death. Per each 0.1 increase in Na:Cl ratio at admission and discharged, there was a 32 % and 54 % higher risk, respectively., Competing Interests: Declaration of competing interest None declared., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objective and Design: Glucocorticoids (GCs) have been widely used in symptomatic patients for the treatment of COVID-19. The risk for adrenal insufficiency must be considered after GC withdrawal given that it is a life-threatening condition if left unrecognized and untreated. Our study aimed to diagnose adrenal insufficiency early on through a GC reduction schedule in patients with COVID-19 infection., Patients and Measurements: From November 2021 to May 2022, 233 patients were admitted to the Geriatric Division of the University Hospital of Padova with COVID-19 infection. A total of 122 patients were treated with dexamethasone, after which the GC tapering was performed according to a structured schedule. It consists of step-by-step GC tapering with prednisone, from 25 mg to 2.5 mg over 2 weeks. Morning serum sodium, potassium, and cortisol levels were assessed 3 days after the last dose of prednisone., Results: At the end of GC withdrawal, no adrenal crisis or signs/symptoms of acute adrenal insufficiency were reported. Median serum cortisol, sodium, and potassium levels after GC discontinuation were, respectively, 427 nmol/L, 140 nmol/L, and 4 nmol/L (interquartile range 395-479, 138-142, and 3.7-4.3). A morning serum cortisol level below the selected threshold of 270 nmol/L was observed in two asymptomatic cases (respectively, 173 and 239 nmol/L, reference range 138-690 nmol/L). Mild hyponatremia (serum sodium 132 to 134 nmol/L, reference range 135-145 nmol/L) was detected in five patients, without being related to cortisol levels., Conclusions: A structured schedule for the tapering of GC treatment used in patients with severe COVID-19 can reduce the risk of adrenal crisis and acute adrenal insufficiency., (© 2024. The Author(s).)

Nephrotic syndrome is a common condition characterized by filtration of large amounts of protein, hypoalbuminemia, reduced plasma oncotic pressure, sodium retention, and edema. The mechanism responsible for sodium retention in this condition is still controversial. Two different pathophysiological pathways have been proposed to explain edema formation: activation of neurohumoral effector mechanisms, including the renin-angiotensin-aldosterone system, or abnormal intrinsic/primary renal sodium retention. A 5-year-old boy with X-linked adrenoleukodystrophy presented with bilateral leg swelling, massive proteinuria, and hypoalbuminemia. Minimal change disease was diagnosed. The patient was initially treated with corticosteroids and experienced several relapses. The progression of fractional excretion of sodium correlated with proteinuria and undetectable aldosterone levels. This unusual finding suggests that the mechanism of tubular sodium avidity in this child with mineralocorticoid insufficiency was independent of the renin-angiotensin-aldosterone system., (© 2024. The Author(s), under exclusive licence to International Pediatric Nephrology Association.)

Background: The optimal management of euvolemic and hypervolemic hyponatremia remains controversial. The effectiveness of the vasopressin receptor antagonist tolvaptan on serum sodium normalization has been well described in the literature, although the associated risk of serum sodium overcorrection limits its use. Urea has been proposed as an alternative treatment option due to its milder serum sodium raising effects and adverse event profile. Objective: This study aimed to compare urea and tolvaptan for their serum sodium raising effects and potential for overcorrection. Methods: In a multicenter retrospective review, 46 hospitalized patients who received either urea or tolvaptan for the management of hyponatremia were evaluated for the rate of serum sodium normalization and overcorrection. Results: Mean serum sodium concentrations at baseline were 125.91 mEq/L and 123.83 mEq/L for patients treated with urea and tolvaptan, respectively. After 12 hours, tolvaptan was associated with a significantly higher rate of serum sodium increase compared with urea (5.05 mEq/L vs 1.10 mEq/L; P = .001). However, no statistically significant differences were observed in the mean change in serum sodium concentrations at 24 hours, 48 hours, or with the proportion of patients who reached a serum sodium concentration of 135 mEq/L. Overcorrection rates were significantly higher with tolvaptan compared with urea at 43% and 9%, respectively. Conclusion: The results of this study suggest that urea has a comparable effectiveness profile to tolvaptan for the management of hyponatremia with a significantly reduced risk of overcorrection., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Abnormal serum Na (SNa) levels are common in patients with chronic kidney disease (CKD) which is associated with increased morbidity and mortality. There are relatively few studies on the effect of SNa indicators on the prognosis of patients undergoing maintenance hemodialysis (MHD). We aim to investigate the effect of long-term SNa levels on the survival and prognosis of patients undergoing hemodialysis (HD). Newly entered HD patients in the registration system of Zhejiang Provincial Dialysis Quality Control Center between January 1, 2010 and December 31, 2019 were included and followed up until December 31, 2020. Multiple sodium levels were collected from patients, defining long-term SNa as the mean of multiple SNa, according to which patients were grouped, with the prognostic differences between subgroups compared by Kaplan-Meier modeling and multifactorial Cox regression modeling. Finally, a total of 21,701 patients were included in this study and Cox regression showed that decreased SNa levels (Na < 135 mmol/L, HR = 1.704, 95% CI 1.408-2.063, p  < 0.001; 135≦Na≦137.5 mmol/L, HR = 1.127,95% CI 1.016-1.250, p  = 0.024) and elevated SNa levels (142.5 < Na≦145mmol/L, HR = 1.198, 95% CI 1.063-1.350, p  = 0.003; Na > 145mmol/L, HR = 2.150, 95% CI 1.615-2.863, p  < 0.001) were all independent risk factors for all-cause mortality in MHD patients.

Background and Subject: Hyponatraemia is a common electrolyte disorder. For patients with severe hyponatraemia, intensive care unit (ICU) admission may be required. This will enable close monitoring and allow safe management of sodium levels effectively. While severe hyponatraemia may be associated with significant symptoms, rapid overcorrection of hyponatraemia can lead to complications. We aimed to describe the management and outcomes of severe hyponatraemia in our ICU and identify risk factors for overcorrection. Materials and Methods: This was a retrospective single-centre cohort that included consecutive adults admitted to the ICU with serum sodium < 120 mmol/L between 1 January 2017 and 8 March 2023. Anonymised data were collected from electronic records. We included 181 patients (median age 67 years, 51% male). Results: Median admission serum sodium was 113 mmol/L (IQR: 108-117), with an average rate of improvement over the first 48 h of 10 mmol/L/day (IQR: 5-15 mmol/L). A total of 62 patients (34%) met the criteria for overcorrection at 48 h, and they were younger, presented with severe symptoms (seizures/arrythmias), and had lower admission sodium concentration. They were more likely to be treated with hypertonic saline infusions. Lower admission sodium was an independent risk factor for overcorrection within 48 h, whereas the presence of liver cirrhosis and fluid restriction was associated with normal correction. No difference was identified between the normal and overcorrected cohorts for ICU/hospital length of stay or mortality. Conclusions: In some patients with severe hyponatraemia, overcorrection is inevitable to avoid symptoms such as seizures and arrhythmias, and consequently, we highlight the key factors associated with overcorrection. Overall, we identified that overcorrection was common and concordant with the current literature.

A 78-year-old man was admitted to the hospital with a 4-day history of fever and confusion. Physical examination revealed oral dryness and decreased skin turgor. Blood tests showed hyponatremia (121.5 ‍mEq/l), and cerebrospinal fluid examination revealed positivity for herpes simplex virus 1 (HSV-1) via polymerase chain reaction. He was diagnosed with herpes simplex encephalitis and initiated acyclovir treatment. The hyponatremia was diagnosed as cerebral salt wasting syndrome (CSWS) and treated with hypertonic saline infusion and fludrocortisone. The cerebrospinal fluid HSV-1 DNA became negative, and the serum sodium levels normalized. Hyponatremia complicated with encephalitis is often caused by the syndrome of inappropriate secretion of antidiuretic hormone (SIADH), whereas CSWS is rare, mostly observed in tuberculous meningitis. Differentiating between the SIADH and CSWS is important as they require distinct therapeutic strategies.

Sodium is crucial for maintaining cardiovascular health, especially in relation to heart failure. The impact of baseline serum sodium concentrations on the outcomes of newly diagnosed coronary heart disease (CHD) without heart failure remains unclear. This prospective cohort study included 681 patients who were newly diagnosed with CHD. Cox proportional hazards models and restricted cubic spline (RCS) analysis were used to assess the relationship between serum sodium concentrations and major adverse cardiovascular events. The improvement in traditional prediction models by the addition of serum sodium concentrations was assessed using changes in the C-statistic, net reclassification improvement (NRI), and integrated discrimination improvement (IDI). During a median follow-up of 51.04 months (IQR: 40.88-53.80 months), 131 events were recorded. Multivariate Cox proportional hazards models showed that the L2 group (136-138.9 mmol/L) had the highest MACE risk. Compared to L2, the hazard ratios (HRs) and 95% confidence intervals (CIs) for the L1 (130-135.9 mmol/L), L3 (139-140.9 mmol/L), L4 (141-142.9 mmol/L), and L5 (143-147.0 mmol/L) groups were 0.31 (0.14-0.70, P = 0.005), 0.48 (030-0.78, P = 0.003), 0.56 (0.34-0.92, P = 0.022), and 0.37 (0.22-0.64, P < 0.001), respectively. Including serum sodium concentrations in the prediction model significantly improved the C-statistic from 0.647 to 0.679 (P = 0.022), with an NRI of 0.338 (P < 0.001) and an IDI of 0.026 (P < 0.001). RCS analysis showed a nonlinear relationship: within the 130-138 mmol/L sodium range, MACE risk gradually increased with higher sodium levels (HR 1.39, 95% CI 1.09-1.76, P = 0.008); whereas within the 138-147 mmol/L range, the risk gradually decreased (HR 0.88, 95% CI 0.80-0.98, P = 0.014). Baseline serum sodium concentrations are significantly associated with long-term cardiovascular risk in newly diagnosed CHD patients, showing an inverted U-shaped relationship, whereas low serum sodium may be specifically linked to higher risks of death and nonfatal myocardial infarction. Further research is needed to explore the impact of long-term changes in serum sodium concentrations on disease prognosis., (© 2024. The Author(s).)

Background: This study aimed to compare the effect of two methods of maintenance intravenous fluid therapy on hyponatremia in hospitalized infants with sepsis., Methods: In a double-blinded randomized clinical trial, 60 term infants with sepsis were enrolled. Blood samples were taken to determine sodium, potassium, Creatinine, and BUN levels before the initiation of treatment. Urine samples were taken to assess specific gravity and urinary output. Infants in the intervention group received half saline in 10% dextrose and infants in the control group were assigned to receive the conventional solution as maintenance. The above indicators were re-evaluated 24 and 48 h after the initiation of treatment. Two groups were compared concerning the incidence of hyponatremia, and other criteria such as urinary output and urinary specific gravity, blood urea nitrogen (BUN), and creatinine levels., Results: Hyponatremia was more common in the control group. Sodium levels were significantly higher in half saline recipients 24 h (137.83 ± 2.86 vs. 134.37 ± 1.91 mmol/L), and 48 h (138.10 ± 2.41 vs. 133.66 ± 1.98 mmol/L) after treatment (P < 0.001). Although BUN in the intervention group was significantly higher in comparison to the control group, the difference in urinary output, urine specific gravity, potassium, and Creatinine levels were not significant in the two groups., Conclusions: The use of a half-saline solution as maintenance fluid reduces the risk of hyponatremia after 48 h when compared to 0.18%NaCl., Trial Registration: This has been registered at Iranian Registry of Clinical Trials (Retrospectively registered, Registration date: 2017-10-12, identifier: IRCT2017053034223N1, https://irct.behdasht.gov.ir/trial/26204 )., (© 2024. The Author(s).)

Objective: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) target the reabsorption of sodium and glucose in the kidney proximal tubules to reduce blood sugar levels. However, clinical randomized controlled trials on SGLT2i have yielded inconsistent results, necessitating further research into their efficacy and safety for specific cardiac and renal diseases., Methods: "Sodium in urine" was selected as a downstream biomarker of SGLT2i. Single nucleotide polymorphisms were extracted from genome-wide association study data as instrumental variables. Mendelian randomization analysis was then conducted for cardiac and renal diseases and potential adverse events. The causal effects of SGLT2i on these diseases were determined based on inverse variance weighted results, followed by sensitivity and pleiotropy tests., Results: SGLT2i had a significant protective effect against nephrotic syndrome (odds ratio [OR] 0.0011, 95% confidence interval [CI] 0.000-0.237), chronic glomerulonephritis (OR 0.0002, 95% CI 0.000-0.21), and hypertensive nephropathy (OR 0.0003, 95% CI 0.000-0.785). No causal effects were observed between SGLT2i and cardiac diseases or potential adverse events., Conclusions: SGLT2i can act as protective factors against nephrotic syndrome, chronic glomerulonephritis, and hypertensive nephropathy., Competing Interests: Declaration of conflicting interestThe authors declare that there is no conflict of interest.

Purpose: This study investigates the association between preoperative serum sodium levels and 30-day postoperative complications following aseptic revision total shoulder arthroplasty (TSA)., Methods: The American College of Surgeons National Surgical Quality Improvement Program database was queried for all patients who underwent aseptic revision TSA from 2015 to 2022. The study population was divided into two groups based on preoperative serum sodium levels: eunatremia (135-144 mEq/L) and hyponatremia (< 135 mEq/L). Logistic regression analysis was performed to investigate the relationship between hyponatremia and early postoperative complications., Results: Compared to eunatremia, hyponatremia was independently associated with a significantly greater likelihood of experiencing any complication (odds ratio [OR] 1.65, 95% confidence interval [CI] 1.14-2.40; P = .008), blood transfusions (OR 2.45, 95% CI 1.24-4.83; P = .010), unplanned reoperation (OR 2.27, 95% CI 1.07-4.79; P = .032), and length of stay > 2 days (OR 1.63, 95% CI 1.09-2.45; P = .017)., Conclusion: Hyponatremia was associated with a greater rate of early postoperative complications following noninfectious revision TSA. This study sheds light on the role of preoperative hyponatremia as a risk factor for postoperative complications and may help surgeons better select surgical candidates and improve surgical outcomes in the setting of revision TSA., (© 2024. The Author(s).)

Background: Reference change values (RCV) are used to indicate a change in analyte concentration that is unlikely to be due to random variation in the patient or the measurement. Current theory describes RCV relative to a first measurement result (X1). We investigate an alternative view predicting the starting point for RCV calculations from X1 and its location in the reference interval., Methods: Data for serum sodium, calcium, and total protein from the European Biological Variation study and from routine clinical collections were analyzed for the effect of the position of X1 within the reference interval on the following result from the same patient. A model to describe the effect was determined, and an equation to predict the RCV for a sample in a population was developed., Results: For all data sets, the midpoints of the RCVs were dependent on the position of X1 in the population. Values for X1 below the population mean were more likely to be followed by a higher result, and X1 results above the mean were more likely to be followed by lower results. A model using population mean, reference interval dispersion, and result diagnostic variation provided a good fit with the data sets, and the derived equation predicted the changes seen., Conclusions: We have demonstrated that the position of X1 within the reference interval creates an asymmetrical RCV. This can be described as a regression to the population mean. Adding this concept to the theory of RCVs will be an important consideration in many cases., (© Association for Diagnostics & Laboratory Medicine 2024. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Several studies reported that exposure to higher levels of fine particulate matter (PM 2.5 ) was associated with deteriorated lipid profiles in children and adolescents. However, whether a sodium-rich diet could modify the associations remains unknown. We aimed to examine the associations of long-term exposure to PM 2.5 with blood lipids in children and adolescents, and further examine the effect modification by dietary and urinary sodium levels based on a multi-community population in China., Methods: The 3711 study participants were from a cross-sectional study, which interviewed children and adolescents aged 6 to 17 years across Sichuan Province, China between 2015 and 2017. Blood lipid outcomes including blood total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglycerides (TG) were assessed. Information on daily dietary sodium consumption was estimated with a semi-quantitative food frequency questionnaire (FFQ), and urinary sodium was used as an internal exposure biomarker. A linear regression model was applied to estimate the associations of prior 2-years' average exposure to ambient PM 2.5 with blood lipids. The effect modification by dietary and urinary sodium was examined by stratified analyses., Results: The participants from rural areas had higher levels of daily sodium consumptions. The results of multivariable regression analysis indicated that per 10 μg/m 3 incremental change in PM 2.5 was associated with a 1.56% (95% confidence interval 0.90%-2.23%) and a 2.26% (1.15%-3.38%) higher blood TC and LDL-C levels, respectively. Among the study participants with higher levels of dietary sodium or urinary sodium, exposure to higher levels of PM 2.5 was significantly associated with deteriorated lipid profiles. For example, each 10 μg/m 3 incremental change in exposure to PM 2.5 was correlated with a 2.83 (-4.65 to -0.97) lower percentage decrease in blood HDL-C levels among the participants who were from the highest quartile of urinary sodium levels. While, these associations changed to be nonsignificant in the participants who were from the lowest quartile of dietary sodium levels., Conclusion: Exposure to higher levels of PM 2.5 was associated with deteriorated blood lipid levels in children and adolescents. It is noteworthy that these associations might be ameliorated through the adoption of a low-sodium dietary regimen., (© 2024. The Author(s).)

Hyponatremia, though common in women with preeclampsia, has not been well studied. Our primary objectives are to assess the clinical characteristics and emergency therapy applied to subjects diagnosed with preeclampsia. We hypothesize that hyponatremia present in preeclamptic patients with severe features is associated with greater use of emergency hypertensives, antenatal steroids, and cesarean delivery. This is a retrospective descriptive study utilizing an electronic health record database (TriNetX ®). We collected and evaluated the following data of subjects aged 15 to 54 years with preeclampsia with severe features diagnosis: demographics, diagnostic codes, medication codes, procedure codes, deaths, and laboratory results. A total of 2,901 subjects [215 (7.4%)] with a sodium level below 134 mEq/L and [2686 (92.6%)] with a sodium level above 135 mEq/L were included. A higher proportion of subjects in the below 134 sodium group received emergency antihypertensives [165 (76.7%) versus 1811 (67.4%), p = 0.01], antenatal steroids [103 (47.9%) versus 953 (35.5%), p = 0.001], and cesarean section [27 (12.6%) versus 97 (3.6%), p = <0.001]. We found that hyponatremia may be associated with emergency antihypertensive use, antenatal steroid use, and cesarean section in patients with preeclampsia with severe features. Future research is needed to determine if routine sodium levels assessed in preeclamptic subjects with severe features identify subjects at risk of receiving these treatments., Competing Interests: Conrad Krawiec receives funding from the New England Journal of Medicine and Elsevier © Osmosis for educational materials and content. The other author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2024 Endres et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

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 ≥140 mEq/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., Competing Interests: GB: Speaker bureau: Astellas, Astrazeneca, Amgen. Patents: n. 4 patents with ST Microelectronics. Travel, Accommodations for scientific conferences: Merck, Janssen. UG: services as advisory/board member of Astellas, Bayer, BMS, IPSEN, Janssen, Merck, Pfizer, Sanofi, received research grant/funding to the institution from AstraZeneca, Roche, Sanofi and travel/accommodations/expenses from BMS BMS, IPSEN, Janssen, Pfizer. LC: has received honoraria for advisory boards, speaker engagements and scientific consultancy for educational purposes from AstraZeneca, EISAI, MSD, Ipsen, BMS, A.A.A.; past MSD employee in Medical Affairs. MS: honoraria as consultant or advisory role from Janssen; grant for participation at scientific events: Astellas Pharma, Sanofi, Roche Novartis, Ipsen, Janssen, Bristol Myers Squibb, Pfizer; research funding: Roche, Merck, Janssen. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Catalano, Rebuzzi, Maruzzo, De Giorgi, Buti, Galli, Fornarini, Zucali, Claps, Chiellino, Zampiva, Pipitone, Ricotta, Sorarù, Mollica, Tudini, Fratino, Prati, Caffo, Atzori, Morelli, Prati, Nolè, Vignani, Cavo, Di Napoli, Malgeri, Naglieri, Signori, Banna, Rescigno, Cerbone, Antonuzzo and Roviello.)

The present study investigated the prevalence of blood chloride (Cl) abnormalities in diarrheic neonatal calves with metabolic acidosis and attempted to identify the most relevant electrolyte abnormality to these abnormalities. A retrospective analysis was conducted on the medical records of 157 diarrheic neonatal calves aged 10.3 ± 4.2 days old with metabolic acidosis. Hypochloremia, normochloremia, and hyperchloremia were observed in 8.9% (14/157), 43.3% (68/157), and 47.8% (68/157), respectively, of diarrheic calves with metabolic acidosis. This distribution remained similar regardless of age (under 8 days or 8 days and older). Furthermore, a multiple logistic regression analysis showed that variations in values for blood sodium [Na (regression coefficients 0.877; 95% confidence interval (CI) 13.977-134.195; P<0.01)], pH (regression coefficients -10.719; 95% CI -19.076- -2.362; P<0.05), and bicarbonate [HCO 3 - (regression coefficients -0.555; 95% CI -0.820- -0.290; P<0.01)] were associated with blood Cl abnormalities. The present results revealed that blood Na concentrations were more strongly associated with blood Cl concentrations than blood pH and HCO 3 - values. In the present study, diarrheic calves with hyperchloremia were characterized by normonatremia and extremely severe metabolic acidosis.

We report a Native American male in his 50s with a complex medical history including alcohol use disorder and seizure disorder who presented with complaints of generalized weakness and multiple falls. The patient was admitted for altered mental status, community acquired pneumonia, sepsis, and bacteremia. On hospital day 23, the patient reported a sudden onset of sensation of food stuck in his upper chest. Brain MRI confirmed osmotic demyelination syndrome (ODS) within the central pons. Further workup revealed this finding was likely due to malnutrition, alcoholism, hypoalbuminemia, and vitamin B6 deficiency. However, the patient presented with normonatremia throughout his entire hospital stay. After acute onset of ODS, the patient was transferred to the ICU where he continued to decline. After 68 days from initial presentation, the patient died in hospice care from myelinolysis complications. This case demonstrates a case of ODS of the central pons in a patient with normonatremia, hypoalbuminemia, and severe vitamin B6 deficiency., (Copyright© South Dakota State Medical Association.)

Background: High-sodium and low-potassium intakes are associated with a higher risk of hypertension and cardiovascular disease, but there are limited data on the circulating metabolomics profiles of 24-h urinary sodium and potassium excretions in free-living individuals., Objectives: We aimed to characterize the metabolomics signatures of a high-sodium and low-potassium diet in a cross-sectional study., Methods: In 1028 healthy older adults from the Women's and Men's Lifestyle Validation Studies, we investigated the association of habitual sodium and potassium intakes measured by 2 to 4 24-h urine samples with plasma metabolites (quantified using liquid chromatography-tandem mass spectrometry) and metabolomic pathways. Our primary exposures were energy-adjusted 24-h urinary sodium excretion, potassium excretion, and sodium-to-potassium ratio, calculated based on energy expenditure derived from the doubly labeled water method. We then assessed the partial correlations of their metabolomics scores, derived from elastic net regressions, with cardiometabolic biomarkers., Results: Higher sodium excretion was associated with 38 metabolites including higher piperine, phosphatidylethanolamine, and C5:1 carnitine. In pathway analysis, higher sodium excretion was associated with enhanced biotin and propanoate metabolism and enhanced degradation of lysine and branched-chain amino acids (BCAAs). Metabolites associated with higher potassium and lower sodium-to-potassium ratio included quinic acid and proline-betaine. After adjusting for confounding factors, the metabolomics score for sodium-to-potassium ratio positively correlated with fasting insulin (Spearman's rank correlation coefficient ρ = 0.27), C-peptide (ρ = 0.30), and triglyceride (ρ = 0.46), and negatively with adiponectin (ρ = -0.40), and high-density lipoprotein cholesterol (ρ = -0.42)., Conclusions: We discovered metabolites and metabolomics pathways associated with a high-sodium diet, including metabolites related to biotin, propanoate, lysine, and BCAA pathways. The metabolomics signature for a higher sodium low-potassium diet is associated with multiple components of elevated cardiometabolic risk., (Copyright © 2024 American Society for Nutrition. Published by Elsevier Inc. All rights reserved.)

Increasing serum osmolality has recently been linked with acute stress responses, which over time can lead to increased risk for obesity, hypertension, and other chronic diseases. Salt and fructose are two major stimuli that can induce acute changes in serum osmolality. Here we investigate the early metabolic effects of sodium and fructose consumption and determine whether the effects of sodium or fructose loading can be mitigated by blocking the change in osmolality with hydration. Forty-four healthy subjects without disease and medication were recruited into four groups. After overnight fasting, subjects in Group 1 drank 500 mL of salty soup, while those in Group 2 drank 500 mL of soup without salt for 15 min. Subjects in Group 3 drank 500 mL of 100% apple juice in 5 min, while subjects in Group 4 drank 500 mL of 100% apple juice and 500 mL of water in 5 min. Blood pressure (BP), plasma sodium, and glucose levels were measured every 15 min in the first 2 h. Serum and urine osmolarity, serum uric acid, cortisol, fibroblast growth factor 21 (FGF21), aldosterone, adrenocorticotropic hormone (ACTH) level, and plasma renin activity (PRA) were measured at the baseline and 2 h. Both acute intake of salt or fructose increased serum osmolality (maximum ∼4 mOsm/L peaking at 75 min) associated with a rise in systolic and diastolic BP, PRA, aldosterone, ACTH, cortisol, plasma glucose, uric acid, and FGF21. Salt tended to cause greater activation of the renin-angiotensin-system (RAS), while fructose caused a greater rise in glucose and FGF21. In both cases, hydration could prevent the osmolality and largely block the acute stress response. Acute changes in serum osmolality can induce remarkable activation of the ACTH-cortisol, RAS, glucose metabolism, and uric acid axis that is responsive to hydration. In addition to classic dehydration, salt, and fructose-containing sugars can activate these responses. Staying well hydrated may provide benefits despite exposure to sugar and salt. More studies are needed to investigate whether hydration can block the chronic effects of sugar and salt on disease., (© 2024. The Author(s).)

Background: Nontraumatic subarachnoid hemorrhage (SAH) can lead to poor neurologic outcomes, particularly when delayed cerebral ischemia (DCI) occurs. Maintenance of euvolemia following SAH is thought to reduce the risk of DCI. However, attempts at maintaining euvolemia often err on the side of hypervolemia. In this study, we assessed the relationship between fluid balance and acute kidney injury (AKI) in SAH patients, assessing hypervolemia versus euvolemia and their impact on AKI. Methods: In a quaternary care center, neuroscience intensive care unit we conducted a retrospective longitudinal analysis in adult patients who suffered a nontraumatic SAH. Results: Out of 139 patients, 15 (10.8%) patients developed an AKI while hospitalized, with 7 stage I, 3 stage II, and 5 stage III injuries. Acute kidney injury patients had higher peak sodium (150.1 mEq/L vs 142.7 mEq/L, 95% confidence interval [CI]: [2.7-12.1 mEq/L]), higher discharge chloride (109.1 mEq/L vs 104.9 mEq/L, 95% CI: [0.7-7.6 mEq/L]), and lower hemoglobin at discharge (9.3 g/dL vs 11.3 g/dL, 95% CI: [1.0-2.9 g/dL]). At 7 days, AKI patients had a fluid balance that was 1.82 L higher ( P  = .04), and 3.38 L higher at 14 days ( P  = .02), in comparison to day 3. Acute kidney injury was associated with significant mortality increases. This increase in mortality was found at 30 days from admission with a 9.52-fold increase, and at 60 days with a 6.25-fold increase. As a secondary outcome, vasospasm (19 patients, 13.7%) showed no association with AKI. Conclusions: Acute kidney injury following SAH is correlated with clinically significant hypervolemia, elevated sodium, elevated chloride, decreased urine output, and decreased hemoglobin at discharge-risk factors for all SAH patients. This study further elucidates the harm of hypervolemia and gives greater practical evidence to physicians attempting to balance the dangers of vasospasm and AKI., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Introduction: Hyponatremia, defined as a serum sodium concentration <135 mmol/l, is a frequent electrolyte disorder in patients presenting to an emergency department (ED). In this context, appropriate diagnostic and therapeutic management is rarely performed and challenging due to complex pathophysiologic mechanisms and a variety of underlying diseases., Objective: To implement a feasible pathway of central diagnostic and therapeutic steps in the setting of an ED., Methods: We conducted a narrative review of the literature, considering current practice guidelines on diagnosis and treatment of hyponatremia. Underlying pathophysiologic mechanisms and management of adverse treatment effects are outlined. We also report four cases observed in our ED., Results: Symptoms associated with hyponatremia may appear unspecific and range from mild cognitive deficits to seizures and coma. The severity of hyponatremia-induced neurological manifestation and the risk of poor outcome is mainly driven by the rapidity of serum sodium decrease. Therefore, emergency treatment of hyponatremia should be guided by symptom severity and the assumed onset of hyponatremia development, distinguishing acute (<48 hours) versus chronic hyponatremia (>48 hours)., Conclusions: Especially in moderately or severely symptomatic patients presenting to an ED, the application of a standard management approach appears to be critical to improve overall outcome. Furthermore, an adequate work-up in the ED enables further diagnostic and therapeutic evaluation during hospitalization.

Background: Timely diagnosis and prevention of diseases require rapid and sensitive detection of biomarkers from blood samples without external interference. Abnormal electrolyte ion levels in the blood are closely linked to various physiological disorders, including hypertension. Therefore, accurate, interference-free, and precise measurement of electrolyte ion concentrations in the blood is particularly important., Results: In this work, a colorimetric sensor based on a biphasic microdroplet extraction is proposed for the detection of electrolyte ions in the blood. This sensor employs mini-pillar arrays to facilitate contact between adjacent blood microdroplets and organic microdroplets serving as sensing phases, with any color changes being monitored through a smartphone's colorimetric software. The sensor is highly resistant to interference and does not require pre-treatment of the blood samples. Remarkably, the sensor exhibits exceptional reliability and stability, allowing for rapid enrichment and detection of K + , Na + , and Cl - in the blood within 10 s (Cl - ), 15 s (K + ) and 40 s (Na + ) respectively., Significance: The colorimetric sensor based on biphasic microdroplet extraction offers portability due to its compact size and ease of operation without the need for large instruments. Additionally, it is location-independent, making it a promising tool for real-time biomarker detection in body fluids such as blood., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)