Plasma Sodium Research Articles

Hyponatremia Associated with the Use of Common Antidepressants in the All of Us Research Program.

Selective serotonin reuptake inhibitor (SSRI), serotonin-norepinephrine reuptake inhibitor (SNRI), and norepinephrine-dopamine reuptake inhibitor (NRI) antidepressants can cause hyponatremia through syndrome of inappropriate antidiuretic hormone secretion (SIADH). This study assesses the differential risks of hyponatremia associated with commonly prescribed SSRIs (fluoxetine, paroxetine, sertraline, citalopram, escitalopram), SNRIs (duloxetine, venlafaxine) and NRI (bupropion), as well as omeprazole as a reference, with a retrospective observational cohort study in the All of Us Research Program, a national multicenter research cohort containing de-identified electronic health records (EHR). Participants who had been prescribed monotherapy with any of eight common antidepressants were included, with each drug considered as a separate arm indexed with a start date. Events were defined as the first occurrence of a low plasma sodium measurement or a clinical diagnosis recorded for either hyponatremia or SIADH. Those who did not have events were censored at their last plasma sodium measurement. A total of 17,439 individuals were exposed to one of the eight antidepressants as monotherapy. The overall incidences for hyponatremia were 0.87% in the first 30 days and 10.5% in the first 3 years in the antidepressant arms. Compared to sertraline, duloxetine (hazard ratio [HR] = 1.37 [1.19-1.58]) and escitalopram (HR = 1.16 [1.01-1.33]) were associated with the highest overall risk of hyponatremia, and bupropion (HR = 0.83 [0.73-0.94]) and paroxetine (HR = 0.78 [0.65-0.93]) were associated with the lowest risk. The risks were unchanged after adjusting for comorbidity and polypharmacy. Such information could help guide providers in managing patients and their risks of hyponatremia when on common antidepressants.

Oxytocin and the Role of Fluid Restriction in MDMA-Induced Hyponatremia: A Secondary Analysis of 4 Randomized Clinical Trials.

3,4-Methylenedioxymethamphetamine (MDMA, or ecstasy) is a recreational drug being investigated for the treatment of posttraumatic stress disorder. Acute hyponatremia is a potentially serious complication after even a single dose of MDMA. The assumed etiology has been a vasopressin release inducing the syndrome of inappropriate antidiuresis combined with increased thirst, causing polydipsia and water intoxication. To investigate the incidence and severity of hyponatremia after a single dose of MDMA, underlying neuroendocrine mechanisms of action, and the potential effect of fluid restriction on lowering the incidence of hyponatremia. This ad hoc secondary analysis pooled data from 4 placebo-controlled crossover randomized clinical trials conducted at the University Hospital Basel, Basel, Switzerland. The 96 participants received experimental doses of MDMA between March 1, 2017, and August 31, 2022. A single oral 100- or 125-mg dose of MDMA. Fluid intake was not restricted in 81 participants; it was restricted in 15. Plasma oxytocin, copeptin (marker of vasopressin), and sodium levels were measured repeatedly within 360 minutes after MDMA intake. The association of plasma oxytocin or copeptin levels with plasma sodium level at 180 minutes (peak concentration of MDMA) was determined. Among the 96 participants, the mean (SD) age was 29 (7) years, and 62 (65%) were men. A total of 39 participants (41%) received a 100-mg dose of MDMA, and 57 (59%) received a 125-mg dose. At baseline, the mean (SD) plasma sodium level was 140 (3) mEq/L and decreased in response to MDMA by 3 (3) mEq/L. Hyponatremia occurred in 30 participants (31%) with a mean (SD) sodium level of 133 (2) mEq/L. In 15 participants with restricted fluid intake, no hyponatremia occurred, while in the 81 participants with unrestricted fluid intake, hyponatremia occurred in 30 (37%) (P = .002) with a difference in plasma sodium of 4 (95% CI, 2-5) mEq/L (P < .001) between both groups, suggesting that fluid restriction may mitigate the risk of hyponatremia. At baseline, the mean (SD) plasma oxytocin level was 87 (45) pg/mL and increased in response to MDMA by 388 (297) pg/mL (ie, a mean [SD] 433% [431%] increase at 180 minutes), while the mean (SD) copeptin level was 4.9 (3.8) pmol/L and slightly decreased, by 0.8 (3.0) pmol/L. Change in plasma sodium level from baseline to 180 minutes demonstrated a negative correlation with the changes in oxytocin (R = -0.4; P < .001) and MDMA (R = -0.4; P < .001) levels while showing no correlation with the change in copeptin level. In this secondary analysis of 4 randomized clinical trials, a high incidence of acute hyponatremia was observed in response to MDMA, which may be mitigated by fluid restriction. Hyponatremia was associated with acute oxytocin but not copeptin release. This challenges the current hypothesis of direct vasopressin release and rather indicates that oxytocin mimics the effect of vasopressin in the kidneys due to structural homology.

Hyponatremia and risk of new-onset heart failure in patients with type 2 diabetes - a real-world study of 70,000 patients

Abstract Background Hyponatremia is common in patients with heart failure and in patients with type 2 diabetes (T2D), and is a risk marker for increased morbidity and mortality. However, it is unclear whether hyponatremia in patients with T2D is associated with an increased risk of new-onset heart failure. Purpose To investigate whether hyponatremia is associated with an increased risk of new-onset heart failure in patients with T2D. Methods From Danish nationwide registers, all patients with T2D with no history of heart failure were identified from 2013-2021. Patients with at least two samples of plasma sodium measured (at least one month apart), during the first six months following their T2D diagnosis, were included with follow-up start six months after T2D diagnosis as well. Patients were categorized in two groups according to the mean plasma sodium concentration at baseline: 1) sodium &amp;gt;137 mmol/L; and 2) sodium &amp;lt;137mmol/L. Cumulative incidence curves and Cox proportional hazards models (crude and adjusted for age, sex, comorbidities, and potential hyponatremia-inducing medications including diuretics, anticonvulsants, and antidepressants) were used to investigate the association of sodium concentration with the incidence of heart failure during follow-up. Incidence rates of heart failure per 1000 person-years were calculated across the spectrum of the measured sodium levels. Results We included 69,750 patients where 57% were male and the median age was 63 (interquartile range: 54-71). At index, 57,723 (83%) patients had a mean sodium concentration of &amp;gt;137 mmol/L and 12,027 (17%) patients had a mean sodium concentration &amp;lt;137 mmol/L (hyponatremia). Patients with a sodium level &amp;lt;137 mmol/L were associated with a significantly higher hazard rate of heart failure compared to patients with sodium concentrations &amp;gt;137 mmol: adjusted hazard ratio (HR) 1.27 (95% confidence interval 1.15-1.41, p-value &amp;lt;0.001). In analyses where sodium concentration was considered a continuous variable, increasing concentration of 1 mmol/L was associated with a decreasing hazard rate of heart failure: adjusted HR 0.96 (0.94-0.97, p-value &amp;lt;0.001). Conclusions Hyponatremia was common and associated with a significantly higher risk of new-onset heart failure in patients newly diagnosed with T2D. Whether hyponatremia could be a new treatment target to prevent heart failure in T2D remains to be determined.Cumulative incidence of heart failureIncident heart failure

Hyponatremia in Critically Ill Patients Due to Continuous Venovenous Hemofiltration With Diluted Sodium Citrate.

Continuous venovenous hemofiltration (CVVH) is frequently performed in critically ill patients using diluted citrate for regional anticoagulation. The impact of this renal replacement strategy on plasma sodium has not been evaluated yet. Our aim was therefore to assess the period prevalence of hyponatremia (sodium <135 mmol/L) during CVVH and discuss possible underlying mechanisms. After 48 hours of treatment, 70% of the 27 oligo-anuric critically ill patients were hyponatremic, despite the use of dialysis fluid bags (Regiocit 18/0, Phoxilium by Baxter, Deerfield, IL, and Multibic K2 by Fresenius Medical Care AG & Co. KGaA, Bad Homburg, Germany) with sodium content of 140 mmol/L. Indeed, sodium decreased from 142 ± 7 to 135 ± 3 mmol/L, p < 0.001. Sodium concentrations of employed dialysis bags were confirmed using ion chromatography. However, ionized sodium of Regiocit measured with a direct-ion selective electrode (ISE) resulted lower (~118 mmol/L), suggesting the presence of sodium-to-citrate complexes. Possible mechanisms explaining the hyponatremia development could therefore include: i) plasma water dilution; ii) a reduced Gibbs-Donnan effect, given the low albumin concentration (2.6 ± 0.8 g/dl) of our critically ill patients; iii) a negative sodium balance due to the loss of sodium-to-citrate complexes across the filter. The clinical implications of the described hyponatremia and the different contributions of the hypothesized mechanisms need to be addressed in future studies.

5042 The Prevalence of Primary Aldosteronism in Incidentally Discovered Adrenocortical Adenomas Irrespective of Blood Pressure: A Prospective Cohort Study

Abstract Disclosure: T. Uslar: None. A. Burnier: None. B. Sanfuentes: None. P. Böhm: None. M. Orellana: None. F.J. Guarda: None. R.I. Olmos: None. Á. Huete: None. N. Mertens: None. C. Besa: None. A. Majerson: None. J. Cartes: None. C.E. Fardella: None. F. Allende: None. S. Solari: None. A. Vaidya: Consulting Fee; Self; Corcept Therapeutics, HRA Pharmaceuticals. R. Baudrand: None. Background: Incidental adrenocortical adenomas are commonly found on imaging. Guidelines recommend screening for primary aldosteronism (PA) only when adrenocortical adenomas are accompanied by hypertension or unexplained hypokalemia. Objective: To prospectively evaluate the prevalence of PA in consecutive patients with incidentally discovered adrenocortical adenomas. Design: Prospective, longitudinal, single-center study. Methods: 254 consecutive patients with incidentally discovered adrenocortical adenomas were studied, without any evidence of autonomous cortisol secretion, excluded via 1mg dexamethasone suppression test. A structured protocol was followed, which involved measurement of plasma aldosterone (PAC), 24h-urinary aldosterone and sodium, plasma renin activity (PRA) and/or direct renin (DRC). Samples were collected in the morning, in a seated posture, after withdrawing interfering medications. Possible PA was defined across a continuum by having a low renin (DRC &amp;lt;10 uIU/mL or PRA &amp;lt; 1ng/mL/hr) in addition to one of the following 3 criteria reflecting the severity of PA: 1) overt PA: aldosterone/renin ratio (ARR) &amp;gt;30, PA &amp;gt;15 ng/dL, and/or 24h urinary aldosterone &amp;gt;10 ug/24h; 2) moderate PA: ARR 20-30 and PAC 10-15 ng/dL; 3) mild PA: ARR &amp;lt;20 and PAC 5-10ng/dL. Adjusted linear regressions were performed. Patients were followed longitudinally to evaluate treatment outcomes with paired T-test. Results: Among patients with incidentally discovered adrenocortical adenomas, 35% (n=89/254) had possible PA. Overt, moderate, and mild PA were identified in 10%, 12%, and 13% of the overall sample, respectively. Notably, one in five of these individuals (20%) were normotensive. There were trends across the 3 phenotypes of PA indicating a continuum of severity, including: systolic blood pressure (152 ±19, 144 ±13, 142 ±16 mmHg, p-trend=0.02), resistant hypertension (56%, 38%, 33% p-trend=0.034), daily defined dose of antihypertensives (DDD) (2.9 ±1.8, 2.1 ±1.5, 1.0 ±0.8 p-trend=0.001), higher PAC (30.7 ±29.4, 10.3 ± 2.7, 7.9 ±2.5ng/dL p-trend&amp;lt;0.001) and urinary aldosterone (18.2 ±12, 5.6 ±3.6, 5.5 ±3.9 ug/24h p-trend&amp;lt;0.001). In longitudinal treatment follow-up (mean 28-months), 83% had a favorable response to treatment (84% medical, 16% adrenalectomy). After treatment, there was a decrease in SBP of -31.3 ±23 mmHg in overt PA, -13.2 ±19 mmHg in moderate PA, and -9.4 ±18 mmHg in mild PA (p&amp;lt;0.001 in all groups). Similar trends were observed for DDD, with a significant increase in renin in all groups. Conclusions: Overt PA, as well as a continuum of PA, was frequently seen in up to 35% of incidentally discovered adrenocortical adenomas. These findings underscore the importance of screening for PA in all patients with adrenocortical adenomas, irrespective of blood pressure and/or hypokalemia. Presentation: 6/1/2024

B-127 The Effect of Hemolysis on Potassium Measurement in a Community Setting: The Marching Error

Abstract Background Potassium is one of the most sensitive analytes to in-vitro hemolysis. To detect this error, modern clinical chemistry analyzers calculate the hemolysis index (HI) to estimate the degree of specimen hemolysis. Recently, Roche Diagnostics lowered the acceptable potassium HI limit from 100 to 20 and recommended laboratories avoid using specimens with an HI&amp;gt;20. The goal of this study was to determine a clinically acceptable HI cut-off for potassium at our community reference laboratory, relying on patient data from routine laboratory operation. Methods Plasma venous potassium, sodium, and HI test results from community patients measured on Roche cobas 8000 ISE and c701 modules between September 2022 to December 2023 were extracted from the Roche Infinity Middleware (n=1,101,897). Data was divided into groups based on HI which ranged from 0 to 300. The sample pool with the lowest level of hemolysis (HI≤10) was defined as the base group. Mean and standard deviation of potassium for each HI group was calculated and the difference in the mean between each group compared to the base group was calculated as both absolute and percent ΔK. Percent changes in critical values for both potassium and sodium as a function of hemolysis were calculated for each HI group. Measurement uncertainty (MU) for potassium was calculated using a top-down approach. Data were analyzed in Rstudio and Microsoft Excel. Results The vast majority of potassium specimens (83.8%) were stratified into the HI base group (HI ≤10) and 96.8 % had an HI ≤ 20, the cut-off recommended by Roche. The mean potassium level for each HI group increased as the degree of hemolysis in the specimens became more elevated. A MU-derived analytically significant shift of ΔK&amp;gt;0.1 mmol/L was observed for the bin HI 21-30. Depending on the employed total allowable error limit, clinically significant shifts in mean potassium levels were observed at HI bin 41-50 (RCPA: ΔK&amp;gt;0.2 mmol/L) or HI bin 101-150 (EFLM-derived reference change value: ΔK&amp;gt;10.1% and CLIA: ΔK&amp;gt;0.5mmol/L. The shift in patient potassium values seen as HI increased led to a change in critical results reporting frequencies. In the base group (HI≤10), 0.06% and 0.07% of results had low (&amp;lt;2.6 mmol/L) or high (&amp;gt;6.2 mmol/L) critical potassium values, respectively. When HI was 101-300, 0.00 and 15.7% of results had low or high critical potassium values. A similar comparison performed with sodium did not show the same shift in reported critical values. Linear regression of ΔK plotted vs HI produced the equation ΔK=0.0051xHI, validating the equation of Martinez-Morillo and Alvarez published previously using paired hemolyzed/non-hemolyzed potassium laboratory data. Conclusions In community patients, in-vitro hemolysis produced analytically significant errors at an HI of 20. Clinically significant errors occurred between an HI of 40-100. Past HI 100, mean ΔKs of 0.5-1.20 mmol/L were seen in our population. This shift in patient values as a function of hemolysis led to a change in critical result reporting, suggesting the generation of both factious critically high potassium results and the masking of critically low potassium results in our patient population.

Plasma Sodium Correction Rates in Patients with Severe Hyponatremia Treated with Hypertonic Saline with and without Desmopressin

Plasma Sodium Correction Rates in Patients with Severe Hyponatremia Treated with Hypertonic Saline with and without Desmopressin

A Comparative Study of Sodium Alginate and Plasma Thrombin Cell Block in Diagnostic Cytopathology.

Background: Cell block is an indispensable supplement in the practice of cytopathology. The diagnostic utility of cytology specimens is significantly impacted by the capacity to generate sufficient cell blocks obtained from concentrated fluid samples or fine-needle aspiration specimens after routine processing. This routine processing involves getting directed passes to produce a cell block, especially if the cytopathologist believes additional immunocytochemical stains and/or molecular studies would be required. Objective: This study compared two methods of cell block preparation: the sodium alginate (SA) method and the plasma thrombin (PT) method. A comparison was made regarding overall cellularity, morphological preservation, and concealed artifacts. Methodology: This cross-sectional study evaluated 104 serous fluid samples and fine-needle aspirates. Cell blocks were prepared for each sample using the plasma thrombin and sodium alginate technique. The formalin-fixed, paraffin-embedded cell blocks were subjected to histochemical staining with hematoxylin and eosin, and slides were assessed for cellularity, artifacts, and morphological preservation. Results: The study utilized chi-square tests to analyze cellularity, morphology, and artifact presence, demonstrating significant differences in cellularity and artifacts between the two methods, with the sodium alginate method showing more cellularity and more artifacts, while morphologically, there was no significantdifference between the two methods. Conclusion: Our study's findings have practical implications for cytopathologists. We conclude that, compared to plasma thrombin methodology, the sodium alginate cell block technique yields higher cellularity, while there was no difference in morphology. Even though artifacts were more prevalent in sodium alginate cell blocks than in plasma thrombin cell blocks, our study suggests that the former can be a better alternative for cell block examination.

Sterile water and regional citrate anticoagulation: A simple CRRT strategy for safe correction of severe hyponatraemia.

Hyponatraemia is a prevalent electrolyte disturbance observed in critically ill patients. The rapid correction of low plasma sodium levels by continuous renal replacement therapy (CRRT) carries the risk of developing osmotic demyelination syndrome (ODS), which can be prevented by implementing an individualized CRRT method. This study aims to introduce a CRRT protocol for the safe and gradual correction of severe hyponatraemia. This retrospective case series study was conducted in an intensive care unit (ICU). All four patients with severe hyponatraemia (<125 mmol/L) and renal failure between October 1, 2022, and September 30, 2023, were treated by CRRT with sterile water and regional citrate anticoagulation (RCA). Data on patient demographics, laboratory biochemical parameters, urine outputs and CRRT-related adverse events were collected. Laboratory parameters and urine outputs were compared by paired t-tests before and after CRRT. After CRRT, sodium levels were significantly increased (112.7 ± 6.7 vs. 141.9 ± 2.8 mmol/L, p = .005). Abnormal urine outputs, potassium, creatinine and bicarbonate were corrected (p for all <.05). Safe and gradual correction of hyponatraemia and internal environmental dysregulation was achieved in all patients without any complications related to CRRT, particularly ODS. It is a novel and simple strategy to correct severe hyponatraemia effectively while ensuring the safety of patients that can be easily implemented by experienced nurse staff. The sterile water-based protocol for postfilter dilution is safe to correct severe hyponatraemia with RCA and can be easily performed by experienced critical care nurses according to the precalculated formula. CRRT-trained, experienced ICU nurses are competent to initiate and adjust sterile water infusion discretely to prevent overcorrection of hyponatraemia.

The efficacy and safety of isotonic and hypotonic fluids in intravenous maintenance fluid therapy in term newborns: national multicenter observational "neofluid" study.

The objective of this study was to evaluate the efficacy and safety of isotonic and hypotonic intravenous fluids in maintenance fluid therapy for term infants. This was a multi-centre, prospective, observational study conducted in 21 participating centres from December 30, 2020, to June 30, 2023. The study included term newborns requiring parenteral fluid therapy for maintenance (NCT04781361). The fluid treatment was divided into two groups based on the concentration of sodium in the parenteral fluid, designated as hypotonic (NaCl <130 mmol/L) and isotonic (NaCl = 130-154 mmol/L). The primary outcomes were the change in mean plasma sodium (pNa) levels per hour (∆pNa mmol/L/h), the incidence of hyponatremia (pNa <135 mmol/L) and hypernatremia (pNa >145 mmol/L), and the occurrence of clinically significant changes in sodium levels (∆pNa >0.5 mmol/L/h). A total of 420 patients from 21 centers were included. The ∆pNa was negative in the hypotonic fluid group and positive in the isotonic fluid group, with a significant difference between the groups [respectively -0.07 ± 0.03 (95% CI: -0.13 to -0.02); 0.04 ± 0.03 (95%CI: -0.02 to 0.09), p = 0.04]. There was no difference between the groups in terms of the development of hypernatremia or a clinically meaningful pNa increase. The hypotonic fluid group had a higher incidence of hyponatremia and a clinically meaningful sodium decrease compared to the isotonic fluid group [7.9% vs. 1.2% (OR:6.5, p:0.03)] and [12.2% vs.4.2% (OR:2.9, p = 0.03)]. Contrary to current understanding, this large-scale study is the first to demonstrate that the use of hypotonic fluids in maintenance fluid therapy for newborns poses a risk of hyponatremia development, whereas isotonic fluid therapy appears safe.

Associations of abnormal fluid status, plasma sodium disorders, and low dialysate sodium with mortality in hemodialysis patients.

Abnormal fluid and plasma sodium concentrations are established prognostic factors for hemodialysis patients. However, the cumulative effects of abnormal salt and water and potential effect modifications and the effect of dialysate sodium remain incompletely understood. The study followed 68,196 incident hemodialysis patients from 875 dialysis clinics in 25 countries over 10 years (2010-2020) investigating dose-response patterns between cumulative exposure time of fluid overload/depletion (measured by bioimpedance spectroscopy using the Fresenius Body Composition Monitor [BCM]), abnormal plasma sodium levels, low dialysate sodium, and all-cause mortality. We calculated time-varying cumulative exposure (in months) of relative fluid overload (any degree; >7% or severe; >13 or >15% in women or men, respectively) and fluid depletion (<-7%), hypo- or hypernatremia (sodium <135 or >145 mmol/L, respectively), low dialysate sodium (≤138 mmol/L), and estimated hazard ratios (HRs) for all-cause mortality using a multivariable Cox model. Of 2,123,957 patient-months, 61% were spent in any degree of fluid overload, 4% in fluid depletion, 11% in hyponatremia, and 1% in hypernatremia. Any degree of fluid overload was associated with higher all-cause mortality (HR peak at 3.42 (95% confidence intervals: 3.12-3.75) relative to no exposure), and this association with all-cause mortality appeared to be stronger with severe fluid overload. The risk pattern associated with hyponatremia was approximately linear in the first four patient-months and then plateaued after the fourth patient-month. We did not observe effect modification between fluid overload and hyponatremia. Even mild fluid overload was associated with higher mortality in hemodialysis patients. Whether a more stringent fluid management results in clinical improvement requires further investigation.

Pain related syndrome of inappropriate antidiuretic hormone secretion in a kitten

A 2-month-old domestic shorthair kitten was presented for evaluation of weakness, gait abnormalities, and signs of pain after trauma. On admission, the patient was found laterally recumbent with obvious gait abnormalities: difficulty rising from sitting and marked unilateral left hind limb lameness. On orthopedic examination, severe pain, crepitations, and swelling of the left hind limb were detected. Results of the first diagnostic work-up were all consistent with hyponatremia, hypochloremia and a Salter-Harris type I fracture.The kitten initially received isotonic fluids, analgesia, and antiemetic treatment. Twelve hours after admission, the analgesic plan was considered insufficient, and the general patient's condition worsened, showing severe mental depression. Blood and urine samples were collected for a more in-depth diagnostic evaluation; the patient showed worsening hyponatremia (113 mmol/L; [RR: 146,2-156,2]), severe plasma hypoosmolality (218.2 mOsm/kg; [RR: 287-307 mOsm/kg]), high natriuresis (Na: 74.9 mmol/L; [RR: <40 mmol/L]), and urinary hyperosmolality (630 mOsm/kg; [RR: <150 mOsm/kg]). Based on these new clinical findings syndrome of inappropriate antidiuretic hormone (SIADH) secretion was diagnosed.Emergency treatment with hypertonic saline was then instituted, a constant rate infusion of 3% hypertonic saline infusion to increase plasma sodium was initiated and a loop diuretic, furosemide (1 mg/kg/IV), was administered at 12-hour intervals to induce diuresis. Discharge occurred 4 days after admission as the patient was clinically stable and the hyponatremia progressively resolved. To the author's knowledge this is the first report of a kitten developing pain related SIADH associated to orthopedic trauma.

Short-Term Effects of Heat Stress on Cow Behavior, Registered by Innovative Technologies and Blood Gas Parameters.

Heat stress (HS) is one of the key factors affecting an animal's immune system and productivity, as a result of a physiological reaction combined with environmental factors. This study examined the short-term effects of heat stress on cow behavior, as recorded by innovative technologies, and its impact on blood gas parameters, using 56 of the 1070 cows clinically evaluated during the second and subsequent lactations within the first 30 days postpartum. Throughout the experiment (from 4 June 2024 until 1 July 2024), cow behavior parameters (rumination time min/d. (RT), body temperature (°C), reticulorumen pH, water consumption (L/day), cow activity (h/day)) were monitored using specialized SmaXtec boluses and employing a blood gas analyzer (Siemens Healthineers, 1200 Courtneypark Dr E Mississauga, L5T 1P2, Canada). During the study period, the temperature-humidity index (THI), based on ambient temperature and humidity, was recorded and used to calculate THI and to categorize the data into four THI classes as follows: 1-THI 60-63 (4 June 2024-12 June 2024); 2-THI 65-69 (13 June 2024-18 June 2024); 3-THI 73-75 (19 June 2024-25 June 2024); and 4-THI 73-78 (26 June 2024-1 July 2024). The results showed that heat stress significantly reduced rumination time by up to 70% in cows within the highest THI class (73 to 78) and increased body temperature by 2%. It also caused a 12.6% decrease in partial carbon dioxide pressure (pCO2) and a 32% increase in partial oxygen pressure (pO2), also decreasing plasma sodium by 1.36% and potassium by 6%, while increasing chloride by 3%. The findings underscore the critical need for continuous monitoring, early detection, and proactive management to mitigate the adverse impacts of heat stress on dairy cow health and productivity. Recommendations include the use of advanced monitoring technologies and specific blood gas parameter tracking to detect the early signs of heat stress and implement more timely interventions.

Rapidly progressive necrotizing enterocolitis: Risk factors and a predictive model.

Rapidly progressive necrotizing enterocolitis (RP-NEC) is a particular subtype of NEC known for its rapid progression and high mortality rate. The objective of this study was to establish a predictive model for RP-NEC. This was a retrospective single-center cohort study. Patients were newborn infants with NEC (Bell's stage ≥ IIB) admitted from January 1, 2016 to December 31, 2023. The primary outcome was RP-NEC defined as the need for surgical intervention and/or death within 48 hours of the onset of NEC. Totally 334 newborn infants were included, among which 82 (24.6%) were RP-NEC cases with a gestation age 34.1 (31.0, 37.0) weeks and birth weight 2100 (1413, 2800) g. Plasma sodium <135 mmol/L, C-reactive protein ≥10 mg/L, platelet count <100 × 109/L, lymphocyte count <1.5 × 109/L, pH <7.2 in blood gas, and ascites at NEC onset were identified as independent risk factors for RP-NEC. The model established presented an AUC value of 0.983 (95% CI 0.97-0.99). The calibration curve for validation was applied revealing a slope close to unity while the Hosmer-Lemeshow test yielded χ2 = 2.550 (p = 0.636). The predictive model established on the above 6 items of RP-NEC is highly promising. Currently, there is a paucity of research on this specific type of severe necrotizing enterocolitis (NEC) characterized by rapid progression. Our study was to investigate the risk factors associated with surgical intervention and/or death within 48 hours following onset in infants with NEC, establish a predictive model for infants with rapidly progressive NEC. The new data presented in this study was the ROC curve combining the above factors as well as hyponatremia.

Hyponatremia in geriatric patients.

Hyponatremia is the most frequent electrolyte imbalance in geriatric medicine. Causes of hyponatremia were retrospectively analyzed in all in-patients treated in 2016 (N = 2267, 1564 women, 703 men, mean age± standard deviation 81.9 ± 7.6years). Any form of hyponatremia on admission, during the stay or on discharge was noted in 308 patients (13.6%, 231 women, 77men; mean age± standard deviation 83.1 ± 7.3 years, p = 0.009 vs. age of all patients). Women had ahigher probability of developing hyponatremia compared to men (p = 0.019), 131 patients were hypovolemic, and dyspnea as an indicator of hypervolemia was noted in 71patients.Only 12patients suffering from hyponatremia (3.9%) did not receive any of the potentially sodium-lowering drugs assessed (diuretics, angiotensin-converting enzyme inhibitors, angiotensinII receptor antagonists, antidepressants, neuroleptics, nonsteroidal antirheumatics, carbamazepine, oxcarbazepine). The median number of drugs per patient potentially lowering the plasma sodium level was3 and the maximum number was7.Hypovolemic hyponatremia and the syndrome of inadequate antidiuretic hormone secretion were the most important causes of hyponatremia. Adverse drug effects were the main origins of both conditions. In patients with hyponatremia the drug load influencing plasma sodium level should be minimized, thiazide diuretics should be avoided and older individuals should receive adiet with sufficient salt content.

Outcomes and relevance of emergency percutaneous coronary angiography and intervention after resuscitated cardiac arrest: a retrospective study

BackgroundIn patients resuscitated from cardiac arrest and displaying no ST-segment elevation on initial electrocardiogram (ECG), recent randomized trials indicated no benefits from early coronary angiography. How the results of such randomized studies apply to a real-world clinical context remains to be established.MethodsWe retrospectively analyzed a clinical database including all patients 18 yo or older admitted to our tertiary University Hospital from January 2017 to August 2020 after successful resuscitation of out-of-Hospital (OHCA) or In-Hospital (IHCA) cardiac arrest of presumed cardiac origin, and undergoing immediate coronary angiography, regardless of the initial rhythm and post-resuscitation ECG. The primary outcome of the study was survival at day 90 after cardiac arrest. Demographic data, characteristics of cardiac arrest, duration of resuscitation, laboratory values at admission, angiographic data and revascularization status were collected. Comparisons were performed according to the initial ECG (ST-segment elevation or not), and between survivors and non-survivors. Variables associated with the primary outcome were evaluated by univariate and multivariate regression analyses.ResultsWe analyzed 147 patients (130 OHCA and 17 IHCA), including 67 with STEMI and 80 without STEMI (No STEMI). Immediate revascularization was performed in 65/67 (97%) STEMI and 15/80 (19%) no STEMI. Day 90 survival was significantly higher in STEMI (48/67, 72%) than no STEMI (44/80, 55%). In the latter patients, survival was not influenced by the revascularization status. In univariate and multivariate analyses, lower age, a shockable rhythm, shorter durations of no flow and low flow, and a lower initial blood lactate were associated with survival in both STEMI and no STEMI. In contrast, metabolic abnormalities, including lower initial plasma sodium and higher potassium were significantly associated with mortality only in the subgroup of no STEMI patients.ConclusionsOur results, obtained in a real-world clinical setting, indicate that an immediate coronary angiography is not associated with any survival advantage in patients resuscitated from cardiac arrest of presumed cardiac etiology without ST-segment elevation on initial ECG. Furthermore, we found that some early metabolic abnormalities may be associated with mortality in this population, which should deserve further investigation.

Podocyte cell-specific Npr1 is required for blood pressure and renal homeostasis in male and female mice: role of sex-specific differences.

Atrial and brain natriuretic peptides (ANP and BNP) bind to guanylyl cyclase A/natriuretic peptide receptor A (GC-A/NPRA), stimulating natriuresis and diuresis and reducing blood pressure (BP), but the role of ANP/NPRA signaling in podocytes (highly specialized epithelial cells covering the outer surfaces of renal glomerular capillaries) remains unclear. This study aimed to determine the effect of conditional deletion of podocyte-specific Npr1 (encoding NPRA) gene knockout (KO) in male and female mice. Tamoxifen-treated wild-type control (PD Npr1 f/f; WT), heterozygous (PD-Cre-Npr1 f/+; HT), and KO (PD-Cre-Npr1 f/-) mice were fed a normal-, low-, or high-salt diet for 4 wk. Podocytes isolated from HT and KO male and female mice showed complete absence of Npr1 mRNA and NPRA protein compared with WT mice. BP, plasma creatinine, plasma sodium, urinary protein, and albumin/creatinine ratio were significantly increased, whereas plasma total protein, albumin, creatinine clearance, and urinary sodium levels were significantly reduced in the HT and KO male and female mice compared with WT mice. These changes were significantly greater in males than in females. On a normal-salt diet, glomerular filtration rate was significantly decreased in PD Npr1 HT and KO male and female mice compared with WT mice. Immunofluorescence of podocin and synaptopodin was also significantly reduced in HT and KO mice compared with WT mice. These observations suggest that in podocytes, ANP/NPRA signaling may be crucial in the maintenance and regulation of glomerular filtration and BP and serve as a biomarker of renal function in a sex-dependent manner.NEW & NOTEWORTHY Our results demonstrate that the podocyte-specific deletion of Npr1 showed increased blood pressure (BP) and altered biomarkers of renal functions, with greater magnitudes in animals fed a high-salt diet in a sex-dependent manner. The results suggest a direct and sex-dependent effect of Npr1 ablation in podocytes on the regulation of BP and renal function and reveal that podocytes may be considered an important target for the ANP-BNP/NPRA/cGMP signaling cascade.

Clinical factors associated with hyponatremia correction during treatment with oral Urea.

Oral urea is being used more commonly to treat hyponatremia, but factors contributing to the correction rate are unknown. We hypothesized that clinically relevant factors can be identified to help guide hyponatremia correction with oral urea. Retrospective study in two university hospitals including hospitalized patients with hyponatremia (plasma sodium < 135mmol/L) treated with oral urea. Linear mixed-effects models were used to identify factors associated with hyponatremia correction. Rates of overcorrection, osmotic demyelination and treatment discontinuation were also assessed. We included 161 urea treatment episodes in 140 patients (median age 69 years, 46% females, 93% syndrome of inappropriate antidiuresis). Oral urea succeeded fluid restriction in 117 treatment episodes (73%), was combined with fluid restriction in 104 treatment episodes (65%) and was given as only treatment in 27 treatment episodes (17%). A median dose of 30 grams/day of urea for 4 days (interquartile range 2-7 days) increased plasma sodium from 127 to 134mmol/L and normalized hyponatremia in 47% of treatment episodes. Older age (ß 0.09, 95%CI 0.02 to 0.16), lower baseline plasma sodium (ß -0.65, 95%CI -0.78 to -0.62), and higher cumulative urea dose (ß 0.03, 95%CI -0.02 to -0.03) were independently associated with a greater rise in plasma sodium. Concurrent fluid restriction was associated with a greater rise in plasma sodium only during the first 48h of treatment (ß 1.81, 95%CI 0.40 to 3.08). Overcorrection occurred in 5 cases (3%), no cases of osmotic demyelination were identified, and oral urea was discontinued in 11 cases (11%) due to side-effects. During treatment with oral urea, older age, higher cumulative dose, lower baseline plasma sodium and initial fluid restriction are associated with a greater correction rate of hyponatremia. These factors may guide clinicians to achieve a gradual correction of hyponatremia with oral urea.

Nephrotic syndrome and adrenoleukodystrophy in a 5-year-old boy.

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.

Edible mushroom (Pleurotus cornucopiae) extract vs. glibenclamide on alloxan induced diabetes: sub-acute in vivo study of Nrf2 expression and renal toxicity.

The study aims to compare the action of Pleurotus cornucopiae and glibenclamide on alloxan-induced diabetes and ascertain how an aqueous extract of the edible mushroom regulates the expression of nuclear factor erythroid 2-related factor 2 (Nrf2), oxidative stress biomarkers and renal toxicity in a diabetic male Wistar rat model. Twenty-five adult male Wistar rats were randomly grouped into five groups with five rats per. Group 1 and those in the treatment groups received normal feed and water ad libitum. Group 2 received intraperitoneal administration of alloxan monohydrate (150 mg/kg body weight). Group 3 received alloxan monohydrate and glibenclamide (5 mg/kg body weight bwt), group 4 received alloxan monohydrate plus the extract (250 mg/kg bwt) and group 5 received alloxan monohydrate plus the extract (500 mg/kg bwt). The administration of glibenclamide plus the extract was oral for 14 days. Glibenclamide and the extract lowered blood glucose level, catalase, and glutathione peroxidase activities, increased the superoxide dismutase (SOD) activity in rats with alloxan induced diabetes. The extract at 500 mg/kg bwt reduced the plasma urea and sodium concentration in the treated rats. The extract and glibenclamide could detoxify alloxan and restore its induced renal degeneration and glomeruli atrophy, intra renal hemorrhage and inflammation and oxidative biomarkers through activation of Nrf2 expression. The drug glibenclamide and P. cornucopiae have appreciable hypoglycemic activity and potential to restore the normal renal architecture in the rats, hence they offer similar curative effects. Additionally, the extract at 500 mg/kg bwt activated SOD and Nrf2 expression more than glibenclamide in rats with alloxan-induced diabetes.