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Background: Osmotic Demyelination Syndrome (ODS) encompasses Central Pontine Myelinolysis and Extrapontine Myelinolysis, both of which are serious neurological conditions linked to the overly rapid correction of hyponatremia. Despite growing evidence, the exact etiology of ODS remains incompletely understood. The present paper describes two case studies, aiming to provide a comprehensive overview of the pathological findings and clinical outcomes associated with ODS., Case Presentation: Case #1. A 74-year-old woman was admitted to the emergency department following a head trauma caused by a loss of consciousness. Initial laboratory tests revealed severe hyponatremia (sodium level of 101 mmol/L) and hypokalemia (potassium level of 2.9 mmol/L). The patient underwent corrective therapy with saline and potassium chloride. Despite the correction of electrolyte imbalances, the patient developed a hyperintense lesion in the median portion of the pons on T2-fluid-attenuated inversion recovery (FLAIR) MRI sequence 14 days post-treatment, consistent with ODS. The patient's condition deteriorated, leading to irreversible coma and status epilepticus, culminating in death 32 days after admission. Case #2. An 81-year-old woman with a medical history of hypothyroidism, hypertension, major depression, and stage 3 chronic kidney disease presented with mild gait disturbances. Subsequent testing revealed severe hyponatremia (sodium level of 100 mmol/L). Following an initial clinical improvement due to sodium correction, the patient's condition worsened, with symptoms progressing to confusion, lethargy, and eventually, ODS. Dermatological manifestations, including blistering lesions and facial edema, appeared as the condition advanced. The patient succumbed to irreversible coma 47 days after admission., Conclusion: ODS traditionally carried a poor prognosis, with high mortality rates and diagnoses often made postmortem. However, recent advances in understanding the pathophysiology, along with improvements in diagnostic techniques such as MRI and intensive care treatments, have led to earlier identification, treatment, and recognition of milder forms of the syndrome. Despite these advancements, ODS remains a critical condition with significant risks, particularly following the rapid correction of severe hyponatremia., (© 2024. The Author(s).)

Osmotic demyelination syndrome (ODS) occurs in patients with diabetes and hyponatremia. We herein report a case of ODS with chorea detected on serial magnetic resonance imaging (MRI), despite no prompt hyponatremia correction. A 74-year-old man with cirrhosis and uncontrolled type 2 diabetes developed an altered mental status and chorea during treatment for diabetic ketoacidosis (DKA). Despite no rapid sodium correction and normal initial brain MRI findings, serial MRI revealed ODS-related abnormalities. Clinicians should consider ODS in patients with DKA and a hyperosmolar hyperglycemic state displaying unconsciousness and neurological manifestations, including chorea, even without substantial changes in serum sodium levels. An MRI re-examination can help capture missing ODS complications.

Afferent baroreflex failure (ABF) is a rare disease. It refers to the clinical syndrome caused by the impairment of the afferent limb of the baroreflex or its central connections at the level of the medulla. The recognized causes include trauma, surgery in related areas (radical neck tumor surgery, carotid endarterectomy), neck radiotherapy, brain stem stroke, tumor growth paraganglioma and hereditary diseases, among which the most common cause is extensive neck surgery or radiotherapy for neck cancer. The main manifestations are fluctuating hypertension, orthostatic hypotension, paroxysmal tachycardia and bradycardia. This case is a young man, whose main feature is blood pressure fluctuation, accom-panied by neurogenic orthostatic hypotension (nOH). After examination, the common causes of hypertension and nOH were ruled out. Combined with the previous neck radiotherapy and neck lymph node dissection, it was considered that the blood pressure regulation was abnormal due to the damage of carotid sinus baroreceptor after radiotherapy for nasopharyngeal carcinoma and neck lymph node dissection, which was called ABF. At the same time, the patient was complicated with chronic hyponatremia. Combined with clinical and laboratory examination, the final consideration was caused by syndrome of in- appropriate antidiuretic hormone (SIADH). Baroreceptors controlled the secretion of heart rate, blood pressure and antidiuretic hormone through the mandatory "inhibition" signal. We speculate that the carotid sinus baroreceptor was damaged after neck radiotherapy and surgery, which leads to abnormal blood pressure regulation and nOH, while the function of inhibiting ADH secretion was weakened, resulting in higher ADH than normal level and mild hyponatremia. The goal of treating ABF patients was to reduce the frequency and amplitude of sudden changes in blood pressure and heart rate, and to alleviate the onset of symptomatic hypotension. At present, drug treatment is still controversial, and non-drug treatment may alleviate some patients' symptoms, but long-term effective treatment still needs further study. The incidence of ABF is not high, but it may lead to serious cardiovascular and cerebrovascular events, and the mechanism involved is extremely complicated, and there are few related studies. The reports of relevant medical records warn that patients undergoing neck radiotherapy or surgery should minimize the da-mage to the baroreceptor in the carotid sinus in order to reduce the adverse prognosis caused by complications.

A man in his 60s presented to the clinic due to night sweats and weight loss following pneumonia. He was found to have hyponatraemia due to a syndrome of inappropriate antidiuretic hormone (SIADH). CT of the thorax was concerning for pulmonary nodules. He was ultimately diagnosed with pulmonary coccidioidomycosis (CM) and started on fluconazole 400 mg daily with improvement in symptoms. Due to the report of headaches, head MRI was conducted which suggested central nervous system (CNS) involvement. Cerebrospinal fluid analysis was consistent with CNS CM and head magnetic resonance angiography confirmed the presence of CNS vasculitis. Fluconazole dose was increased to 800 mg daily which the patient continued to tolerate and showed improvement. This report depicts a case of SIADH associated with CNS CM with vasculitis and demonstrates the importance of high clinical suspicion for SIADH secondary to CNS CM in the setting of hyponatraemia and headache., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Rationale: Cyclophosphamide (CTX) is widely used in the treatment of malignancies and autoimmune diseases. Although severe hyponatremia caused by low-dose CTX chemotherapy is uncommon, it can lead to serious complications and even death., Patient Concerns: A 44-year-old woman with left-sided breast cancer suddenly experienced headaches, disorientation and weakness after receiving low-dose neoadjuvant chemotherapy combined with CTX and doxorubicin., Diagnoses: The patient pathology showed invasive breast carcinoma. She developed severe hyponatremia and a generalized seizure after completing the first cycle of neoadjuvant chemotherapy with CTX and doxorubicin. Laboratory tests showed a serum sodium of 118 mmol/L (normal range 135-145 mmol/L) and potassium sodium 3.16 mmol/L (normal range 3.5-5.5 mmol/L). Subsequently, the patient developed secondary diabetes insipidus 4 hours after sodium supplementation, her 24-hour urine volume was 4730 mL (normal range 1000-2000 mL/24 hours), and the urine specific gravity decreased to 1.005., Interventions: The patient was given intravenous sodium chloride (500 mL of 3%NaCl, 100 mL/hour) and potassium chloride (500 mL of 0.3%KCl, 250 mL/hour). Meanwhile, she was advised to reduce her water intake, and pituitrin was administered to prevent dehydration caused by diabetes insipidus., Outcomes: The patient completely recovered after correcting of the serum sodium concentration (137 mmol/L) without any neurological deficits. After discontinuing pituitrin, her 24-hour urine volume was 2060 mL and the urine specific gravity was 1.015., Lessons: This is a typical case of severe hyponatremia induced by low-dose CTX. Clinicians and healthcare providers should be aware of this potential toxicity, and appropriate monitoring should be implemented., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Coronavirus disease 2019 (COVID-19) due to a severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection can include various systemic organ disorders including endocrinopathies and neurological manifestations. We report the case of a 65-year-old Japanese man who developed isolated adrenocorticotropic hormone (ACTH) deficiency and encephalopathy following SARS-CoV-2 infection. Two weeks after his COVID-19 diagnosis, he was emergently admitted to our hospital because of subacute-onset delirium. On admission, he presented hyponatremia (128 mEq/L) and secondary adrenal insufficiency (ACTH <1.5 pg/mL, cortisol 0.53 μg/dL). Brain imaging and laboratory examinations including SARS-CoV-2 polymerase chain reaction testing in the cerebrospinal fluid revealed no abnormalities. His consciousness level worsened despite the amelioration of hyponatremia by intravenous hydrocortisone (100 mg/day), but his neurological presentations completely resolved after three consecutive days of high-dose (400 mg/day) hydrocortisone. His encephalopathy did not deteriorate during hydrocortisone tapering. He continued 15 mg/day hydrocortisone after discharge. His encephalopathy might have developed via a disturbance of the autoimmune system, or a metabolic effect associated with adrenal insufficiency, although the time lag between the hyponatremia's improvement and the patient's neurological response to the steroid was incompatible with common cases of delirium concurrent with adrenal insufficiency. At 13 months after his hospitalization, the patient's neurological symptoms have not recurred and he has no endocrinological dysfunctions other than the remaining ACTH deficiency. A thorough consideration of the immunological and metabolic characteristics of SARS-CoV-2 is advisable when clinicians treat patients during and even after their COVID-19 disease period.

Background: Reports on COVID-19 in peritoneal dialysis (PD) patients are scarce in China. This study aimed to describe the characteristics and outcomes of PD patients with COVID-19 after China abandoned the 'zero-COVID' policy., Methods: This single-centre retrospective study included patients receiving PD who underwent testing for COVID-19 infections between 7 December 2022 and 7 January 2023. Outcomes of interest included factors associated with positive COVID-19 testing result and clinical outcomes including COVID-19-related hospitalisation and severe COVID-19, which were analysed using logistic regression analyses., Results: A total of 349 PD patients (male 53.6%, age 49 ± 13 years old) were included, and 235 patients (67.3%) were infected. There were no significant differences between COVID-19 and non-COVID-19 patients other than higher proportion of vaccinated patients and slow transporters in the patients who tested positive for COVID-19 (44.7% vs. 28.1%, p = 0.003; 8.7% vs. 1.8%, p = 0.03, respectively). Multivariate analysis showed COVID-19 was associated with vaccination (odds ratio (OR): 1.71, 95% confidence interval (CI): 1.02-2.86) and slow transport type (compared with average transport type, OR: 4.52, 95% CI: 1.01-20.21). Among the patients with infection, 38 (16.2%) patients were hospitalised, 18 (7.7%) patients had severe disease and 9 (3.8%) patients died. In multivariate logistic analysis, both age (OR: 1.04, 95% CI: 1.01-1.07; OR: 1.06, 95% CI: 1.02-1.11) and hyponatremia (OR: 5.44, 95% CI: 1.63-18.13; OR: 6.50, 95% CI: 1.77-23.85) were independent risk factors for COVID-19-related hospitalisation and severe disease., Conclusions: Although vaccinated patients were more likely to have tested positive for COVID-19 infection, they appeared to have less severe infection and less need for hospitalisation. Patients who were older with a history of hyponatremia were more likely to experience adverse outcomes from COVID-19., 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.

Objectives: This study investigated the association between hyponatremia and falls in elderly hospitalized patients, focusing on mild hyponatremia as a potential risk factor., Materials and Methods: A retrospective analysis of 16,952 patients admitted to Kochi Medical School Hospital from 2012 to 2021 was performed. Serum sodium levels were categorized, and falls during a 30-day observation period were recorded. A Cox proportional hazards model and a machine learning model were used to estimate risk and explore interactions., Results: Mild hyponatremia (130-134 mEq/L) was identified as an independent risk factor for falls (hazard ratio: 1.42, 95 % confidence interval 1.16-1.74), especially in patients with higher activities of daily living. The fall prediction model showed an area under the curve (AUC) of 0.780 (95 % confidence interval 0.751-0.806)., Conclusion: A significant association between mild hyponatremia and falls in elderly hospitalized patients was found. The findings highlight the need for targeted fall prevention and further research into the underlying mechanisms. Mild hyponatremia may serve as a clinical marker for fall risk, especially in patients with independent activities of daily living., Competing Interests: Declaration of Competing Interest None declared., (Copyright © 2023. Published by Elsevier B.V.)

Objective: Almost two thirds of the world's aneurysmal subarachnoid hemorrhage (aSAH) are in low- and middle-income countries. Herein, we aimed to evaluate the impact of complications on the outcome of aSAH in a middle-income country., Methods: Baseline data (age, sex, World Federation of Neurosurgical Society, time ictus-treatment, treatment modality) and medical and neurologic complications from a cohort in Brazil (2016-2019) were evaluated: delayed cerebral ischemia; hydrocephalus; meningitis; seizures; intracranial hypertension; infections (pneumonia, bloodstream, urinary tract infection infection of undetermined source); sodium disturbances; acute kidney injury; and cardiac and pulmonary complications. The primary outcome was the modified Rankin scale (mRS) at hospital discharge. Univariate and multivariate models were employed., Results: From 212 patients (71.7% female, age 52.7 ± 12.8), 92% developed at least 1 complication (any infection-43.9%, hydrocephalus-34.4%, intracranial hypertension-33%, infection of undetermined source-20.8%, hypernatremia-20.8%, hyponatremia-19.8%, delayed cerebral ischemia-related infarction-18.7%, pneumonia-18.4%, acute kidney injury-16.5%, and seizures-11.8%). In unadjusted analysis, all but hyponatremia and urinary tract infection were associated with mRS 3-6 at discharge; however, complications explained only 12% of the variation in functional outcome (mRS). Most patients were treated by clipping (66.5%), and 15.6% (33 patients) did not receive a definitive treatment. The median time ictus-admission and ictus-treatment were 5 and 9 days, respectively., Conclusions: While medical and neurologic complications are a recognized opportunity to improve aSAH care, low- and middle-income countries comprise 70% of the world population and still encounter difficulties concerning early definitive aneurysm treatment, rebleeding, and human and material resources., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background and Purpose: In patients with acute ischemic stroke, hyponatremia (plasma sodium < 136 mmol/L) is common and associated with unfavorable outcomes. However, data are limited for patients who underwent intravenous thrombolysis (IVT) and/or endovascular thrombectomy (EVT). Therefore, our aim was to assess the impact of hyponatremia on postreperfusion outcomes., Methods: We analyzed data of consecutive patients who presented with acute ischemic stroke and were treated with IVT and/or EVT at Isala Hospital, the Netherlands, in 2019 and 2020. The primary outcome measure was the adjusted common odds ratio (acOR) for a worse modified Rankin Scale (mRS) score at 3-month follow-up. Secondary outcomes included symptomatic intracranial hemorrhage, in-hospital mortality, infarct core, and penumbra volumes., Results: Of the 680 patients (median age = 73 years, 49% female, median National Institutes of Health Stroke Scale = 5), 430 patients (63%) were treated with IVT, 120 patients (18%) with EVT, and 130 patients (19%) with both. Ninety-two patients (14%) were hyponatremic on admission. Hyponatremia was associated with a worse mRS score at 3 months (acOR = 1.76, 95% confidence interval [CI] = 1.12-2.76) and in-hospital mortality (aOR = 2.39, 95% CI = 1.23-4.67), but not with symptomatic intracranial hemorrhage (OR = 1.17, 95% CI = 0.39-3.47). Hyponatremia was also associated with a larger core (17.2 mL, 95% CI = 2.9-31.5) and core to penumbra ratio (55.0%, 95% CI = 7.1-102.9)., Conclusions: Admission hyponatremia in patients with acute ischemic stroke treated with IVT and/or EVT was independently associated with unfavorable postreperfusion outcomes, a larger infarct core, and a larger core to penumbra ratio. Future studies should address whether correction of hyponatremia improves the prognosis., (© 2023 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Purpose: To investigate the clinical characteristics of the syndrome of inappropriate antidiuretic hormone (SIADH) associated with nasal and paranasal malignant tumors., Methods: Patients with locally advanced or recurrence/metastatic malignant tumors of the nasal and paranasal sinuses were included. The SIADH was diagnosed according to the diagnostic criteria. The clinical characteristics of SIADH patients were retrospectively analyzed., Results: Six patients (6/188, 3.2%) met the diagnostic criteria of SIADH, including four olfactory neuroblastoma (4/26, 15.4%), one neuroendocrine carcinoma (1/9, 11.1%), and one squamous cell carcinoma (1/63, 1.6%). Five patients (83.3%) had severe hyponatremia; however, the hyponatremia could be improved by fluid restriction or tolvaptan. Three patients' SIADH were recovered during the chemotherapy and the other three were recovered after the surgery., Conclusion: The incidence of SIADH associated with nasal and paranasal malignant tumors is relatively more common in olfactory neuroblastoma and neuroendocrine carcinoma. The hyponatremia caused by SIADH may be corrected by fluid restriction or tolvaptan, and the SIADH may be recovered through anti-tumor therapy., (© 2023. The Author(s).)

Objectives: Midodrine, an oral α-1-adrenergic receptor agonist, counters arterial hypovolemia and reduces complications in adult patients with cirrhosis. This randomized controlled trial (RCT) aimed to assess the efficacy and safety of midodrine in preventing complications and improving survival in children with cirrhosis and ascites who are awaiting liver transplantation (LT)., Methods: This open-label RCT conducted from January 2022 to May 2023 included children under 18 years with cirrhosis and ascites. Patients were randomized to receive either midodrine plus standard medical therapies (SMTs) or SMT alone. The primary outcome measure was the incidence of cirrhosis-related complications within 6 months., Results: Thirty-five subjects were enrolled and randomized. Patients in the midodrine arm had a lower incidence of new-onset acute kidney injury (AKI) compared with the SMT arm (11.1% vs. 41.2%). Patients in the midodrine arm showed a decline in serum creatinine and improvement in glomerular filtration rate, whereas no changes were observed in the SMT arm. There was a lower incidence of new-onset hyponatremia in the midodrine arm (20% vs. 56%). Midodrine led to reduction in plasma rennin activity (PRA) and improvement in systemic hemodynamics. There was no difference in the rate of resolution of ascites, recurrence of ascites, requirement of therapeutic paracentesis, cumulative albumin infusion requirement, episodes of spontaneous bacterial peritonitis, and hepatic encephalopathy between the two arms., Conclusion: Midodrine, when added to SMT, was effective in reducing the incidence of new-onset AKI and hyponatremia in pediatric cirrhotics awaiting LT. It also improved systemic hemodynamics and showed a trend towards reducing PRA., (© 2023 European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Aim: To identify the symptoms and relevant factors associated with acute adrenal insufficiency of early-onset Sheehan syndrome., Methods: We retrospectively reviewed the charts of 125 women admitted to our intensive care unit because of postpartum hemorrhage between January 2011 and December 2021. Three women developed acute adrenal insufficiency. We investigated the total blood loss, shock status, consciousness level upon arrival, and intensive care provided to the women. We also analyzed the symptoms and laboratory data that led to the diagnosis of acute adrenal insufficiency. Continuous variables were presented by median (minimum-maximum)., Results: The medians and ranges of age, total blood loss, and shock index [heart rate/systolic blood pressure] on admission were 33.1 (17.2-45.3) years, 3351 (595-20 260) g, and 0.94 (0.55-2.94), respectively. Seven women were older than 40 years, 28 experienced >5000 g blood loss, 17 had shock index >1.5, 27 had impaired consciousness upon arrival, and 15 underwent hysterectomy. Women who developed acute adrenal insufficiency were <40 years old and had a bleeding volume of over 5000 g, impaired consciousness upon arrival, and had undergone hysterectomy. They had experienced lactation failure, presented with hyponatremia-related symptoms on postpartum days 8-9, experienced general malaise, headache, and impaired consciousness, and showed severe hyponatremia., Conclusions: Massive postpartum hemorrhage over 5000 g, impaired consciousness upon arrival, and hysterectomy as a hemostatic measure were relevant factors associated with acute adrenal insufficiency of early-onset Sheehan syndrome. Hyponatremia-related symptoms occurring after lactation failure are indicative of the onset of acute adrenal insufficiency., (© 2023 Japan Society of Obstetrics and Gynecology.)

Background: The prognostic association between dysnatremia and outcomes in out-of-hospital cardiac arrest (OHCA) is not well understood. Given hypernatremia is associated with poor outcomes in critical illness and hyponatremia may exacerbate cerebral edema, we hypothesized that dysnatremia on OHCA hospital admission would be associated with worse neurological outcomes., Methods: We studied adults (≥19 years) with non-traumatic OHCA between 2009 and 2016 who were enrolled in the British Columbia Cardiac Arrest Registry and survived to hospital admission at 2 quaternary urban hospitals. We stratified cases by admission serum sodium into hyponatremic (<135 mmol/L), normonatremic (135-145 mmol/L), and hypernatremic (>145 mmol/L) groups. We used logistic regression models, adjusted for age, sex, shockable rhythm, admission serum lactate, and witnessed arrest, to estimate the association between admission sodium and favorable neurological outcome (cerebral performance category 1-2 or modified Rankin scale 0-3)., Results: Of 414 included patients, 63 were hyponatremic, 330 normonatremic, and 21 hypernatremic. In each respective group, 21 (33.3%), 159 (48.2%), and 3 (14.3%) experienced good neurological outcomes. In univariable models, hyponatremia (OR 0.53, 95% CI 0.30-0.93) and hypernatremia (OR 0.19, 95% CI 0.05-0.65) were associated with lower odds of good neurological outcomes compared to the normonatremia group. After adjustment, only hypernatremia was associated with lower odds of good neurological outcomes (OR 0.22, 95% CI 0.05-0.98)., Conclusions: Hypernatremia at admission was independently associated with decreased probability of good neurological outcomes at discharge post-OHCA. Future studies should focus on elucidating the pathophysiology of dysnatremia following OHCA., (Crown Copyright © 2023. Published by Elsevier Inc. All rights reserved.)

Aim: To investigate the value of hyponatremia as a predictive marker for complicated appendicitis. Methods: PubMed, Embase, Web of Science and Scopus databases were searched for studies published up to 5 June 2024. Studies reporting serum sodium levels in patients with complicated and non-complicated appendicitis and studies reporting the association between baseline hyponatremia and complicated appendicitis were included. A random-effects meta-analysis was performed. Results: Twenty-two studies met the eligibility criteria. Serum sodium levels were measured at arrival or preoperatively in all included studies. Meta-analysis of data from 17 studies showed that preoperative sodium levels were significantly lower in patients with complicated appendicitis vs uncomplicated appendicitis [Mean Difference (MD): -2.58 95% confidence intervals (CI): -3.51, -1.66 I 2  = 98%]. A pooled analysis of 18 studies demonstrated a statistically significant association between preoperative hyponatremia and complicated appendicitis [Odds Ratio (OR): 4.11 95% CI: 3.07, 5.51 I 2  = 93%]. Results remained significant on subgroup analysis for adult and pediatric populations. However, the MD was higher and the OR was higher in the subgroup of pediatric patients. Conclusion: Hyponatremia was identified as a potential predictor for complicated appendicitis. The association between hyponatremia and complicated appendicitis seems to be stronger in pediatric patients as compared with adults.

Hyponatremia is a common electrolyte abnormality with important prognostic and therapeutic implications. It might exert detrimental effects on various organ systems including the central nervous system (CNS), bone, and heart along with its potential association with poor quality of life. These adverse effects might be largely mediated through a variety of mechanisms including osmotic stress, dysfunctional transmembrane exchangers, and enhanced oxidative stress.Interestingly, hyponatremia might also have an important association with takotsubo syndrome (TTS) that has been universally considered as a reversible form of cardiomyopathy usually emerging in response to various stressors. In this context, severe hyponatremia was previously reported to serve as a direct trigger of TTS evolution largely through its potential impact on CNS and heart. However, pathogenetic and clinical implications of hyponatremia still need to be thoroughly evaluated in patients with TTS. This paper aims to analyze the clinical features of published cases with TTS primarily triggered by hyponatremia and also aims to discuss the association between hyponatremia and TTS from a broader perspective., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Rare mutations in NADH:ubiquinone oxidoreductase complex assembly factor 5 (NDUFAF5) are linked to Leigh syndrome., Objective: We aimed to describe clinical characteristics and functional findings in a patient cohort with NDUFAF5 mutations., Methods: Patients with biallelic NDUFAF5 mutations were recruited from multi-centers in Taiwan. Clinical, laboratory, radiological, and follow-up features were recorded and mitochondrial assays were performed in patients' skin fibroblasts., Results: Nine patients from seven unrelated pedigrees were enrolled, eight homozygous for c.836 T > G (p.Met279Arg) in NDUFAF5 and one compound heterozygous for p.Met279Arg. Onset age had a bimodal distribution. The early-onset group (age <3 years) presented with psychomotor delay, seizure, respiratory failure, and hyponatremia. The late-onset group (age ≥5 years) presented with normal development, but slowly progressive dystonia. Combing 25 previously described patients, the p.Met279Arg variant was exclusively identified in Chinese ancestry. Compared with other groups, patients with late-onset homozygous p.Met279Arg were older at onset (P = 0.008), had less developmental delay (P = 0.01), less hyponatremia (P = 0.01), and better prognosis with preserved ambulatory function into early adulthood (P = 0.01). Bilateral basal ganglia necrosis was a common radiological feature, but brainstem and spinal cord involvement was more common with early-onset patients (P = 0.02). A modifier gene analysis showed higher concomitant mutation burden in early-versus late-onset p.Met279Arg homozygous cases (P = 0.04), consistent with more impaired mitochondrial function in fibroblasts from an early-onset case than a late-onset patient., Conclusions: The p.Met279Arg variant is a common mutation in our population with phenotypic heterogeneity and divergent prognosis based on age at onset. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society., (© 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.)

BACKGROUND Diffusion tensor imaging (DTI) is an advanced magnetic resonance imaging (MRI) method used to identify changes in microstructures in the brain's white matter. Severe brain injuries after trauma are associated with disorders of consciousness (DOC) and may result in hyponatremia due to damage to the hypothalamus. This case-control study aimed to use DTI to evaluate the hypothalamus in 36 patients with hyponatremia and DOC due to severe brain injuries. MATERIAL AND METHODS Thirty-six patients with DOC after traumatic brain injury (TBI) and 36 healthy control subjects were enrolled in this study. The diagnosis of DOC was based on the coma recovery scale-revised (CRS-R). The 36 patients were divided into 2 groups: Group A (18 with hyponatremia, serum sodium level <135 mmol/L) and group B (18 without hyponatremia). The DTI scans were conducted using a 6-channel head coil on a 1.5T Philips Gyroscan Intera scanner. Among the DTI data, fractional anisotropy (FA) and the apparent diffusion coefficient (ADC) of the hypothalamus were analyzed. RESULTS Patient group A had a lower FA value (P=0.044) and higher ADC value (P=0.004) of the hypothalamus and showed a longer length of hospital stay (P=0.03), lower CRS-R score at discharge (P=0.01), and less change in CRS-R score (P=0.004) compared to patient group B. The improvements in the CRS-R score revealed a moderate negative correlation (r=-0.467) with the severity of the hyponatremia (P=0.004). CONCLUSIONS Post-traumatic hyponatremia was associated with hypothalamic injury and the presence and severity of hyponatremia were associated with poor clinical outcomes in DOC patients.

Rationale: Neuromyelitis optica spectrum disorder (NMOSD) is a demyelinating disease that causes lesions in areas with abundant aquaporin-4 (AQP4) channels, including the hypothalamus. Hypothalamic lesions can disrupt antidiuretic hormone regulation, resulting in hyponatremia due to syndrome of inappropriate antidiuretic hormone (SIADH). Various factors can trigger NMOSD, including viral infections. We report the case of a young female patient who presented with hyponatremia due to SIADH and was found to have bilateral hypothalamic lesions along with positive serum herpes simplex virus immunoglobulin M., Patient Concerns: An 18-year old female patient presented with fever and nausea that had persisted for 5 days. Three days after hospitalization, the patient complained of blurred vision, hiccups, and excessive daytime sleepiness., Diagnosis: The patient hyponatremia was attributed to SIADH. Magnetic resonance imaging revealed bilateral lesions in the hypothalamus, and serum laboratory tests were positive for herpes simplex virus immunoglobulin M. On the 15th day of admission, the anti-AQP4 antibody test result was positive, leading to the diagnosis of NMOSD., Interventions: On the initial suspicion of herpes encephalitis, treatment with acyclovir was initiated. However, upon the confirmation of after anti-AQP4 antibody, the patient was additionally treated with a high-dose intravenous steroid for 5 days., Outcomes: The patient fever, nausea, visual disturbances, and other complaints improved within 1 week of initiating steroid treatment., Lessons: In young patients presenting with hyponatremia and suspected SIADH accompanied by neurological abnormalities, it is crucial to differentiate central nervous system diseases, including NMOSD, which can involve lesions in AQP4-abundant areas, such as the hypothalamus., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Introduction: Appendicolithiasis is a risk factor for perforated acute appendicitis. There is limited inpatient data on predictors of progression in appendicolithiasis-associated non-perforated acute appendicitis., Methods: We identified adults presenting with appendicolithiasis-associated non-perforated acute appendicitis (on computed tomography) who underwent appendectomy. Logistic regression was used to investigate predictors of in-hospital perforation (on histopathology)., Results: 296 patients with appendicolithiasis-associated non-perforated acute appendicitis were identified; 48 (16.2%) had perforation on histopathology. Mean (standard deviation [SD]) age was 39 (14.9) years. The mean (SD) length of stay (LOS) was 1.5 (1.8) days. LOS was significantly longer with perforated (mean [SD]: 3.0 [3.1] days) vs. non-perforated (mean [SD]: 1.2 [1.2] days) appendicitis (p < 0.001). On multivariate analysis, in-hospital perforation was associated with age > 65 years (OR 5.4, 95% CI: 1.4- 22.2; p = 0.015), BMI > 30 kg/m2 (OR 3.5, 95% CI: 1.3-8.9; p = 0.011), hyponatremia (OR 3.6, 95% CI: 1.3-9.8; p = 0.012). There was no significant association with age 25-65 years, gender, race, steroids, time-to- surgery, neutrophil percentage, or leukocyte count., Conclusion: Geriatric age, obesity, and hyponatremia are associated with progression to perforation in appendicolithiasis-associated non-perforated acute appendicitis., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: Early and accurate preoperative diagnosis of complicated appendicitis mandates the identification of new markers. The aim of this study is to determine whether preoperative serum sodium levels are useful for predicting the severity of acute appendicitis., Methods: We retrospectively analyzed 475 patients who underwent emergency appendectomies between January 2018 and February 2023 in a general hospital in Brazil. The patients were divided into 2 groups: complicated (n = 254) and uncomplicated (n = 221). Hyponatremia was defined as serum sodium levels < 136 mEq/L. The primary outcome was to evaluate if hyponatremia is associated with complicated appendicitis., Results: The patients had a median age of 22 years, and the median serum sodium level was 137 mEq/L in patients with complicated appendicitis and 139 mEq/L in uncomplicated appendicitis (P < 0.001). The analysis of the receiver operating characteristic curve used as the best cutoff value of serum sodium of 136 mEq/L with a sensitivity of 45.7%, specificity of 86.4%, positive predictive value of 79.5%, and negative predictive value of 58.1% for the diagnosis of complicated AA. Of the 254 patients with complicated appendicitis, 84 (33.1%) had serum sodium levels below 136 mEq/L, while only 12 (5.4%) patients with uncomplicated appendicitis had values ​​below this cutoff. Patients with hyponatremia were 5 times more likely to develop complicated appendicitis. (odds ratio: 5.35; 95% confidence interval: 3.39-8.45) CONCLUSIONS: Preoperative serum sodium levels are a useful tool for predicting the severity of acute appendicitis. Due to its low cost and wide availability, it has become an extremely relevant marker., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Purpose: Distinguishing between perforated/gangrenous from uncomplicated appendicitis in children helps management. We evaluated hyponatremia as a new diagnostic marker for perforated/gangrenous appendicitis in children., Methods: A prospective study including all children with acute appendicitis who underwent appendectomy at our institution from May 2021 to May 2023. Medical history and clinical criteria were analyzed. All blood samples were taken upon admission including serum inflammatory markers and electrolytes. Patients were divided into two groups (Group I: uncomplicated and Group II: perforated/gangrenous), and data between both groups were compared., Results: The study included 153 patients [Group I: 111 (73%), Group II: 42 (27%)]. Mean serum sodium concentration in children with perforated/gangrenous appendicitis was significantly lower compared to children with uncomplicated appendicitis (131.8 mmol/L vs. 138.7 mmol/L; p < 0.001). The ROC curve of preoperative sodium level to differentiate between perforated/gangrenous and uncomplicated appendicitis revealed an AUC of 0.981. The cut-off-value of sodium level < 135 mmol/L identified perforated/gangrenous appendicitis with a sensitivity of 94% and a specificity of 91% (p < 0.001). Predictive factors of perforated/gangrenous appendicitis were: age less than 5 years (12% vs. 3%; p = 0.02), experiencing symptoms for more than 24 h (100% vs. 58%; p < 0.001), body temperature more than 38.5 °C (52% vs. 13%; p < 0.001), a serum sodium level less than 135 mmol/L (90% vs. 6%; p < 0.001), and a CRP serum level more than 50 mg/L (71% vs. 17%; p < 0.001)., Conclusions: Hyponatremia, upon admission, is a novel, objective biochemical marker that can identify perforated/gangrenous appendicitis in children. We advocate that the assessment of serum sodium level should be added to the diagnostic algorithm in children with suspected acute appendicitis. Surgical intervention in patients with hyponatremia should not be delayed, and non-operative management should be avoided., (© 2023. The Author(s).)

Objectives: To demonstrate the role of inferior vena cava (IVC) collapsibility in the assessment of volume status in hyponatremic critically ill patients in the emergency department (ED) with bedside IVC imaging and to predict volume status with response to fluid therapy., Methods: A prospective 110 hypotonic hyponatremic patients aged >18 years with a serum sodium level under 125 mEq/L and at least one symptom of hyponatremia, who presented or referred to the ED was conducted. Demographical, clinical, and laboratory characteristics with bedside measurement of IVC diameter of patients were recorded. Volume status was divided into 3 subgroups: hypovolemic-G1, euvolemic-G2, and hypervolemic-G3. An ED trainee with a certification to perform basic and advanced ultrasonography (USG) training carried out the USG examinations. A diagnostic algorithm approach was made according to the results., Results: Symptom severity was significantly greater in the hypervolemic group than the other groups (P = .009 and P = .034, respectively). Systolic blood pressure (SBP) and mean arterial pressure (MAP) were significantly lower in the hypovolemic group compared with the other groups (P < .001 and P = .003, respectively). There was a significant difference between the ultrasonographically measured IVC min, IVC max, and mean IVC values across the three volume-based groups (P < .001)., Conclusion: Considering the diversity of physical examination (PE) findings, with the highly heterogenous nature of hyponatremia, a new measurable algorithm can be developed on the basis of contemporary hyponatremic patient management guidelines., (© 2023 American Institute of Ultrasound in Medicine.)

Background: hyponatremia represents one of the most commonly encountered conditions in hospitalized patients, multiple mechanisms being cited so far, neoplastic syndromes being an important cause. The aim of the current paper is to analyse the presence and influence of the short- and long-term outcomes of hyponatremia on ovarian cancer patients submitted to surgery for advanced stage ovarian cancer. Method: 57 patients diagnosed with advanced stage ovarian cancer were submitted to surgery between 2014-2020. The patients were further classified according to the preoperative value of sodium into two groups. Results: there were 21 cases with preoperative normal values of sodium and respectively 36 cases with hyponatremia. Patients with preoperative hyponatremia associated a significantly higher rate of early postoperative complications and a significantly poorer long-term outcome. Therefore, cases with hyponatremia reported a mean disease-free survival of 10.8 months and respectively a mean overall survival of 18.5 months while cases with normal natrium levels reported a mean disease-free survival of 31.4 months and respectively a mean overall survival of 49.7 months (p=0.0001 and p 0.001). Conclusions: patients with lower preoperative values of sodium have a higher risk of developing postoperative complications and a significantly poorer outcome when compared to cases presenting normal levels of sodium preoperatively., (Celsius.)

Hyponatremia is a common clinical problem in older people. The aging process is usually accompanied by various maladaptations to stress in different organs and physiologic functions. Medications are often the cause of hyponatremia such as thiazide diuretics, antidepressants, antiepileptic and antipsychotics. Antipsychotics can lead to severe hyponatremia by the mechanism of the development of the syndrome of inappropriate antidiuretic hormone secretion (SIADH). We report a patient who presented with severe hyponatremia due to Chlorpromazine and improved after receiving corrective hyponatremia.

Background: Hyponatremia is a common electrolyte disorder in patients with chronic kidney disease. In addition, hyponatremia is associated with mortality in patients with chronic kidney disease, including those on dialysis. However, few studies have examined this relationship in patients with incident dialysis., Methods: We used a database of multicenter prospective cohort studies that included 1520 incident dialysis patients. The baseline was set at the time of dialysis initiation. The enrolled patients were classified into five groups according to their serum sodium levels (< 130 mEq/L, 130-134 mEq/L, 135-139 mEq/L, 140-144 mEq/L, and ≥ 145 mEq/L). Multivariate Cox proportional hazards analysis was conducted to determine factors associated with all-cause mortality., Results: A total of 392 all-cause deaths occurred during the follow-up period. The ultrafiltration volume per body weight during the first dialysis session was more significant in the groups with the lowest and highest sodium levels. The percentage of patients using loop diuretics and thiazide was higher in the group with lower sodium levels (< 130 mEq/L and 130-134 mEq/L). All-cause mortality was significantly different among the five groups (p = 0.025). Multivariate analysis indicated that all-cause mortality was significantly higher in the group with the lowest sodium level compared to the group with a serum sodium level of 135-139 mEq/L (hazard ratio: 1.61, 95% confidence interval: 1.04-2.49)., Conclusion: Hyponatremia of < 130 mEq/L at dialysis initiation was significantly associated with all-cause mortality. We considered the results relevant to underlying conditions, including cardiovascular disease and medications., (© 2023. The Author(s), under exclusive licence to The Japanese Society of Nephrology.)

The syndrome of inappropriate ADH-secretion (SIADH) is a common cause of low sodium levels with diverse aetiology. Here, we report a case of a 41 years old male patient diagnosed with SIADH and a good response to Tolvaptan therapy. Of interest, as a potential unique cause, magnetic resonance imaging revealed a micronodular structure in the posterior pituitary, while no other common cause of SIADH could be identified. Hence, to the best of our knowledge, this is the first case of a Tolvaptan-responsive SIADH associated with a pituitary micronodular structure., Competing Interests: The authors declare that they have no conflict of interest., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

Aims: To comprehensively assess hyponatraemia in acute heart failure (AHF) regarding prevalence, associations, hospital course, and post-discharge outcomes., Methods and Results: Of 8298 patients in the European Society of Cardiology Heart Failure Long-Term Registry hospitalized for AHF with any ejection fraction, 20% presented with hyponatraemia (serum sodium <135 mmol/L). Independent predictors included lower systolic blood pressure, estimated glomerular filtration rate (eGFR) and haemoglobin, along with diabetes, hepatic disease, use of thiazide diuretics, mineralocorticoid receptor antagonists, digoxin, higher doses of loop diuretics, and non-use of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers and beta-blockers. In-hospital death occurred in 3.3%. The prevalence of hyponatraemia and in-hospital mortality with different combinations were: 9% hyponatraemia both at admission and discharge (hyponatraemia Yes/Yes, in-hospital mortality 6.9%), 11% Yes/No (in-hospital mortality 4.9%), 8% No/Yes (in-hospital mortality 4.7%), and 72% No/No (in-hospital mortality 2.4%). Correction of hyponatraemia was associated with improvement in eGFR. In-hospital development of hyponatraemia was associated with greater diuretic use and worsening eGFR but also more effective decongestion. Among hospital survivors, 12-month mortality was 19% and adjusted hazard ratios (95% confidence intervals) were for hyponatraemia Yes/Yes 1.60 (1.35-1.89), Yes/No 1.35 (1.14-1.59), and No/Yes 1.18 (0.96-1.45). For death or heart failure hospitalization they were 1.38 (1.21-1.58), 1.17 (1.02-1.33), and 1.09 (0.93-1.27), respectively., Conclusion: Among patients with AHF, 20% had hyponatraemia at admission, which was associated with more advanced heart failure and normalized in half of patients during hospitalization. Admission hyponatraemia (possibly dilutional), especially if it did not resolve, was associated with worse in-hospital and post-discharge outcomes. Hyponatraemia developing during hospitalization (possibly depletional) was associated with lower risk., (© 2023 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Objective: To assess the demographic and clinical characteristics, laboratory findings, and economic burden of patients with a diagnosis of complicated skin and soft tissue infection (cSSTI)., Method: The demographic and clinical characteristics, laboratory findings, surgical interventions, cost of treatment, and outcome of patients diagnosed with cSSTIs between January 2017 and December 2019 were retrospectively analysed., Results: A total of 24 patients with cSSTIs were included in the study. The median age was 53 (22-85) years, and 14 (58%) were female. The most common comorbidity was diabetes (54%). On admission, 75% of patients presented with sepsis, and 70% had a high-grade Laboratory Risk Indicator for Necrotising Fasciitis (LRINEC) score. The causative microorganism was isolated from 21 (87%) patients, and the multidrug resistance rate of Gram-negative bacteria was 50%. The median number of debridements was 3 (1-12). In all, 11 patients were followed up in the intensive care unit, and the mortality rate was 29%. The presence of confusion (p=0.025), causative Gram-negative microorganisms (p=0.009), hyponatraemia (p=0.034), the need for intensive care (p=0.001), anti-meticillin-resistant Staphylococcus aureus antibiotics (p=0.023) and the rate of antibiotic changes during treatment (p=0.019) were significantly higher in the non-survival patient group. Hyponatraemia was a significant independent risk factor for mortality (p=0.048). The median cost of per-patient treatment was $9453 USD in the non-surviving and $1536 in the surviving group., Conclusion: It is important to know possible factors and local resistance rates at the beginning of empirical antibacterial and surgical treatment. The presence of hyponatraemia, sepsis and a high LRINEC score can be considered to be the mortality predictors.

BackgroundTolvaptan poses a significant risk to patient safety due to its risk of overcorrection of hyponatremia, and its cost-effectiveness is not well established. Kettering Health implemented order questions into Epic in 2019 to drive appropriate use of tolvaptan. Objective: The primary objective was to determine the impact of implementing order questions on appropriate use of tolvaptan. The secondary objectives were to determine if providers are adhering to the order questions meant to ensure appropriate use, to identify if there is provider variance across the network constituting a higher proportion of use outside of network recommendations, and to look at patients with multiple orders for tolvaptan and discern if dose titration was appropriate based on sodium levels. Methods: This study was a retrospective chart review of all patients who received a dose of tolvaptan from 7/3/2019 to 10/15/2020. Results: From July 2019 to October 2020, 211 patients received tolvaptan for hyponatremia, resulting in 598 administrations. Use of urea powder or fluid restriction preceded 248/586 (42.3%) tolvaptan administrations and the patient's sodium level was < 125 mEq/L or 125-135 mEq/L with documentation of symptoms for 261/586 (44.5%) of the administrations. Medication safety concerns related to monitoring sodium levels were also identified. Conclusions: While tolvaptan use did significantly decrease in Kettering Health since the implementation of order questions, the answers to the questions displayed substantial variability. Further opportunity exists for directing appropriate use of tolvaptan within Kettering Health and additional emphasis should be placed on safe use of this medication.

Background: Dysnatremia is a common disorder in critically ill surgical children. The study's aim is to determine the prevalence of dysnatremia and its association with outcomes after surgery for congenital heart disease (CHD)., Methods: This is a single-center retrospective cohort study of children <18 years of age undergoing surgery for CHD between January 2012 and December 2014. Multivariable logistic regression analysis was used to evaluate the relationship between dysnatremia and outcomes during the perioperative period. A total of 1345 encounters met the inclusion criteria., Results: The prevalence of pre- and post-operative dysnatremia were 10.2% and 47.1%, respectively. Hyponatremia occurred in 19.1%, hypernatremia in 25.6%. Hypernatremia at 24, 48, and 72 h post-operative was associated with increased hospital mortality (odds ratios (OR) [95% confidence intervals (CI)] 3.08 [1.16-8.17], p = 0.024; 4.35 [1.58-12], p = 0.0045; 4.14 [1.32-12.97], p = 0.0148, respectively. Hypernatremia was associated with adverse neurological events 3.39 [1.12-10.23], p = 0.0302 at 48 h post-operative. Hyponatremia was not associated with any adverse outcome in our secondary analysis., Conclusions: Post-operative dysnatremia is a common finding in this heterogeneous cohort of pediatric cardiac-surgical patients. Hypernatremia was more prevalent than hyponatremia and was associated with adverse early post-operative outcomes., Impact: Our study has shown that dysnatremia was highly prevalent in children after congenital heart surgery with hypernatremia associated with adverse outcomes including mortality. It is important to understand fluid and sodium regulation in the post-operative period in children with congenital heart disease to better address fluid overload and associated electrolyte imbalances and acute kidney injury. While clinicians are generally very aware of the importance of hyponatremia in critically ill children, similar attention should be given to hypernatremia in this population., (© 2023. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)

Hyponatremia is a well-established marker of adverse outcomes in chronic heart failure (HF) but not well studied in patients with left ventricular assist device (LVAD). This is a retrospective study, single center study of HM3 [Abbott, USA] LVAD implants. We divided our population based on their sodium prior to LVAD implantation - hyponatremia if <135 mEq/L and normal sodium if 135-145 mEq/L. We compared postoperative and long-term outcomes. A total of 195 patients were included, preimplant hyponatremia was present in 40% with a sodium of 132.1 ± 2.1 vs 137.8 ± 1.9 mEq/L in the normal sodium group. No differences were observed in the postoperative or long-term outcomes. Preimplant hyponatremia was not associated with mortality or HF admissions, likely due to adequate left ventricular unloading and resolution of the mechanisms that lead to hyponatremia. These results suggest that optimization of mild hyponatremia may not be critical and should not delay LVAD placement., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Hyponatremia is the most common electrolyte disorder in lung cancer, and it particularly occurs in small cell lung cancer (SCLC) patients. The prognostic significance of hyponatremia has been reported in several studies with controversial results., Aims: We aimed in this study to investigate hyponatremia and evaluate its prognostic value in SCLC patients., Methods: The data of 373 SCLC patients were analyzed retrospectively. Serum sodium concentrations were measured from blood samples taken from all patients before treatment. Hyponatremia was defined as a serum sodium concentration below 135 mmol/L and then assigned into two groups: mild (130 to 134 mmol/L) and severe (below ≤ 129 mmol/L) hyponatremia., Results: Hyponatremia was detected in 85 (22.8%) patients (mild hyponatremia in 51 (13.7%) and severe hyponatremia in 34 (9.1%) patients). Furthermore, 26% (63 of 242) of ED-SCLC patients and 16.8% (22 of 131) of LD-SCLC patients had hyponatremia. While no clinical parameter was statistically associated with serum sodium concentrations in LD-SCLC patients, hyponatremic ED-SCLC patients were more frequently associated with weight loss (p = 0.04) and liver metastasis (p = 0.04). In LD-SCLC, the overall survival (OS) rates of patients with hyponatremia were similar to those with normonatremia (p = 0.6). Likewise, hyponatremic and normonatremic ED-SCLC patients had similar life expectancies (p = 0.1). Moreover, the severity of hyponatremia did not affect OS in either LD-SCLC (p = 0.3) or ED-SCLC (p = 0.1)., Conclusion: Serum sodium concentration did not have an impact on survival in SCLC patients; thus, we concluded that neither the presence nor the severity of hyponatremia affected the outcome of these patients., (© 2022. The Author(s), under exclusive licence to Royal Academy of Medicine in Ireland.)

While it was previously believed that neuromyelitis optic spectrum disorder (NMOSD) mostly affected the optic nerves and the spinal cord, it is increasingly recognized that NMOSD can involve any area of the CNS where aquaporin-4 is highly expressed. These other areas can include the hypothalamus and the circumventricular organs that surround the third and fourth ventricles, serving as osmoregulators. The syndrome of inappropriate antidiuretic hormone secretion (SIADH) is one of the most common causes of hyponatremia and has been associated with NMOSD due to these lesions. In this report, we present a case of a patient with known NMOSD, who presented with dizziness, fatigue, and generalized weakness and whose workup revealed hyponatremia in the setting of SIADH and hypothalamic demyelinating lesions. This case illustrates an atypical presentation of NMOSD and the importance of looking for syndromes, such as SIADH. This can guide diagnostic testing, such as getting thin MRI cuts through the hypothalamus and brainstem, as well as advanced management techniques such as immunotherapy., (© 2023 American Academy of Neurology.)

Introduction: This systematic review and meta-analysis examined the relationship between hyponatremia and worse outcomes in patients undergoing maintenance hemodialysis., Methods: The MEDLINE, EMBASE, CENTRAL, and Web of Science databases were used to search for relevant articles. The target population was patients on maintenance hemodialysis (those undergoing hemodialysis for ≥60 days). The defined outcomes were death, cardiovascular disease, cognitive decline, and falls. Meta-analysis was performed with a random-effects model of pairwise comparisons of normonatremia and hyponatremia defined for each study, 1-mmol/L increment of sodium analysis, and dose-response analysis using the sodium concentration defined for each study. This study was registered with PROSPERO (registration number CRD42018087667)., Results: Thirteen articles were included. The pairwise analysis revealed that the hazard ratio for all-cause mortality was 1.45 (95% confidence interval, 1.31-1.61). The analysis of 1-mmol/L increment of sodium included six studies with a hazard ratio for all-cause mortality of 0.94 (95% confidence interval, 0.91-0.97) for each 1-mmol/L increase in the serum sodium concentration. In the dose-response analysis, assuming a linear relationship, a sodium increment of 1 mmol/L revealed a hazard ratio for all-cause mortality of 0.97 (95% confidence interval, 0.96-0.98). Other outcomes could not be integrated., Conclusions: Hyponatremia is associated with all-cause mortality in patients undergoing maintenance hemodialysis. Healthcare providers should pay special attention to even the slightest indication of hyponatremia., (© 2023 Wiley Periodicals LLC.)

Fructose has recently been proposed to stimulate vasopressin secretion in humans. Fructose-induced vasopressin secretion is not only postulated to result from ingestion of fructose-containing drinks but may also occur from endogenous fructose production via activation of the polyol pathway. This raises the question of whether fructose might be involved in some cases of vasopressin-induced hyponatremia, especially in situations where the cause is not fully known such as in the syndrome of inappropriate secretion of diuretic hormone (SIADH) and exercise-associated hyponatremia, which has been observed in marathon runners. Here we discuss the new science of fructose and vasopressin, and how it may play a role in some of these conditions, as well as in the complications associated with rapid treatment (such as the osmotic demyelination syndrome). Studies to test the role of fructose could provide new pathophysiologic insights as well as novel potential treatment strategies for these common conditions., (Published by Elsevier Inc.)

A man in his late 40s with no significant medical history presented with 2 weeks of lethargy, nausea and dizziness, alongside worsening headaches. Initial assessment revealed severe hyponatraemia and secondary hypothyroidism; urgent MRI pituitary was requested with a clinical suspicion of pituitary apoplexy. This demonstrated a likely cystic pituitary adenoma, with further testing revealing pituitary gland suppression, leading to a diagnosis of chronic secondary hypopituitarism. Initiating hormone replacement allowed substantial reported improvements in this patient's quality of life.A review of the patient's work-up revealed areas in which best practice was not followed. Cortisol measurements and paired urinary and serum osmolalities were initially not sent, nor results appropriately chased. A subsequent literature review identified that conformation with national and local guidelines on hyponatraemia management is poor. This patient's case, when combined with the literature review, provides evidence to support methods to increase educational awareness of an appropriate work-up of hyponatraemia among clinicians., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Competing Interests: Conflict of interest: None declared.

Amiodarone is an antiarrhythmic drug belonging to Vaughan-Williams Class III with additional Class IV effects, which is known to cause many adverse drug reactions (ADRs) necessitating close monitoring. In about 20% of patients, their therapy is discontinued due to adverse effects such as hepatic impairment, thyroid dysfunction, and several pulmonary complications. Although dyselectrolytemia is a common adverse reaction reported with many cardiac medications, the incidence of hyponatremia associated with amiodarone intake is not reported widely in the literature. We are reporting a case of a 73-year-old female patient, with hypertension and ischemic heart disease (IHD) receiving oral amiodarone, presenting with severe hyponatremia, requiring recurrent hospitalization. Amiodarone was found to be responsible after evaluating for the possible causes of hyponatremia. As the incidence of amiodarone-associated hyponatremia is unknown, and not many cases are reported, this case report serves to sensitize the clinician to consider amiodarone-induced hyponatremia as one of the differential diagnoses in cases of unexplained hyponatremia.

Background: Patients with cirrhosis are at high risk of mortality after organ failure that requires ICU care. There have been attempts to predict which patients are at highest risk, with some success found in adapting liver disease-specific scoring systems with clinical variables commonly associated with critical illness. However, the clinical factors predictive of which patients with cirrhosis are most at-risk of needing ICU level care are unknown., Aims: Our study set out to better understand which clinical variables were associated with need for ICU care in patients with cirrhosis., Methods: Retrospective analysis of admitted patients with cirrhosis at single tertiary care center., Results: Patients with cirrhosis admitted to our center were categorized into three groups: those without ICU transfer, those admitted to the ICU directly from the emergency department (ED), and those admitted to the ICU from the medicine floor. These groups differed in mortality at 30 days (3.5% vs. 15% vs. 25%, P < 0.001) and at subsequent intervals up to 1 year. These groups differed in indication for ICU transfer, with GI bleed, hemorrhagic shock, hepatic encephalopathy, and hyponatremia occurring more in the ED-to-ICU group, while respiratory failure was more common in the floor-to-ICU group. In multivariable analysis, factors associated with ICU transfer included worsened kidney function, anemia, hyponatremia, leukocytosis, and the decision to obtain a lactate level. Similar analysis with only floor-to-ICU patients found that ICU transfer was associated with hypoalbuminemia, hyponatremia, hypotension, and SIRS score., Conclusion: Our study found significant differences in mortality among three distinct groups of patients with cirrhosis. A risk factor model for ICU transfer found that variables both specific and nonspecific to liver disease were associated with ICU transfer, with between-group differences supporting the idea of different clinical phenotypes and suggesting factors that should be considered in early triage and assessment of hospitalized patients with cirrhosis., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Aim: To explore the relationship between the serum sodium level on admission and all-cause mortality in HF patients., Design: A single-center retrospective cohort study., Methods: Patients hospitalized with HF at the Heart Failure Center, Fuwai Hospital, from November 2008 to November 2018 were enrolled., Results: A total of 3649 patients were included, and the mean sodium level was 137.19 ± 4.36 mmol/L, with a range from 115.6 to 160.9 mmol/L. During a median follow-up of 1101 days, mortality occurred in 1413 (38.7%) hospital survivors. After adjustment for age, sex, and other potential confounders, patients with sodium levels <135 mmol/L (hazard ratio [HR]: 1.67; 95% confidence interval [CI]: 1.29-2.16) and 135-137 mmol/L (HR: 1.34; 95% CI: 1.01-1.78) had an increased risk of all-cause mortality compared to those with sodium levels of 139-141 mmol/L., (© 2023 The Authors. Nursing Open published by John Wiley & Sons Ltd.)

Aneurysmal subarachnoid hemorrhage (aSAH) is a devastating neurological condition. Endovascular coiling or surgical clipping have equivocal success rates, but relatively little is known regarding the health economics and complications of these procedures at the population level. We aimed to analyze the complication profiles and healthcare resource utilization (HRCU) associated with the treatment of aSAH in the USA. We performed a retrospective analysis utilizing the IBM MarketScan database between 2008 and 2015. Primary outcomes included economic analysis stratified by post-operative complication; determination of the effect of several factors on total cost by multivariable regression; and analysis of the incidence, timing, and associated HCRU of aSAH-related post-operative complications. Of the 2374 patients meeting inclusion criteria for economic analysis, 1783 (75.1%) patients had at least one of the ten complications. The most common complications included hydrocephalus (43.8%), transient cerebral ischemia (including vasospasm) (30.6%), ischemic stroke (29.1%), syndrome of inappropriate antidiuretic hormone (SIADH)/hyposmolarity/hyponatremia (22.1%), and seizures (14.9%). Patients who experienced complications had higher median 90-day total costs [$161,127 (Q1 to Q3, $101,411 to $257,662)] than those who did not [$97,376 (Q1 to Q3, $55,692 to $147,447)]. Length of stay was longest for those with pulmonary embolism and pneumonia (27 days) and shortest for those with SIADH/hyposmolarity/hyponatremia (16 days). Brain compression/herniation had the highest mortality rate (19.5%). In total, 14.6% of all patients experienced a readmission within 30 days. In conclusion, patients with aSAH have high post-operative complication rates and costs. Development of novel interventions to reduce complications and improve outcomes is crucial., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Pulmonary complications are the most common adverse event after lung resection, yet few large-scale studies have examined pertinent risk factors after video-assisted thoracoscopic surgery (VATS) lobectomy. Veterans, older and less healthy compared with nonveterans, represent a cohort that requires further investigation. Our objective is to determine predictors of pulmonary complications after VATS lobectomy in veterans., Methods: A retrospective review was conducted on patients who underwent VATS lobectomy from 2008 to 2018 using the Veterans Affairs Surgical Quality Improvement Program database. Patients were divided into two cohorts based on development of a pulmonary complication within 30 days. Patient characteristics were compared via multivariable analysis to determine clinical predictors associated with pulmonary complication and reported as adjusted odds ratios (aORs) with 95% confidence intervals. Patients with preoperative pneumonia, ventilator dependence, and emergent cases were excluded., Results: In 4,216 VATS lobectomy cases, 480 (11.3%) cases had ≥1 pulmonary complication. Preoperative factors independently associated with pulmonary complication included chronic obstructive pulmonary disease (COPD) (aOR = 1.37 [1.12-1.69]; p  = 0.003), hyponatremia (aOR = 1.50 [1.06-2.11]; p  = 0.021), and dyspnea (aOR = 1.33 [1.06-1.66]; p  = 0.013). Unhealthy alcohol consumption was associated with pulmonary complication via univariable analysis (17.1 vs. 13.0%; p  = 0.016). Cases with pulmonary complication were associated with increased mortality (12.1 vs. 0.8%; p  < 0.001) and longer length of stay (12.0 vs. 6.8 days; p  < 0.001)., Conclusion: This analysis revealed several preoperative factors associated with development of pulmonary complications. It is imperative to optimize pulmonary-specific comorbidities such as COPD or dyspnea prior to VATS lobectomy. However, unhealthy alcohol consumption and hyponatremia were linked with development of pulmonary complication in our analysis and should be addressed prior to VATS lobectomy. Future studies should explore long-term consequences of pulmonary complications., Competing Interests: None declared., (Thieme. All rights reserved.)

Background: A recent study reported the effect of preoperative hyponatremia on postoperative outcomes of patients with non-small cell lung cancer. However, the influence of postoperative hyponatremia on postoperative outcomes has not been completely investigated., Methods: We retrospectively studied 75 octogenarians who underwent pulmonary surgery for non-small cell lung cancer between 2009 and 2018. We divided them into hyponatremic and non-hyponatremic groups, depending on preoperative and immediate postoperative serum sodium levels, and investigated their clinicopathological characteristics and outcomes. Disease-specific survival and cumulative incidence of relapse rates between the two groups were calculated and compared using the stratified Kaplan-Meier method. Univariable and multivariable analyses were performed to identify prognostic factors., Results: Preoperative hyponatremia was associated with 66.7% of postoperative respiratory and 88.9% of non-cardiovascular complications. The long-term prognosis of the postoperative hyponatremic group was significantly worse than that of their counterpart. The 3-year disease-specific survival and 3-year cumulative incidence of relapse rate were 55.9% and 46.2%, respectively, and the median observation period after surgery was 37.4 (interquartile range, 23.7-51.0) months for the entire cohort. Kaplan-Meier curves showed that hyponatremia was associated with worse disease-specific survival and cumulative incidence of relapse. Multivariable analysis identified hyponatremia as a factor that predicted unfavorable disease-specific survival and cumulative incidence of relapse., Conclusions: Immediate postoperative hyponatremia is an independent predictor of non-small cell lung cancer outcomes among octogenarians. Preoperative hyponatremia was associated with a high frequency of postoperative respiratory and non-cardiovascular complications. Surgical indications in older patients with hyponatremia should be carefully considered with follow-up., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Hyponatremia is frequent in older age; whether it is a key player, a surrogate marker, or an innocent bystander in age-related diseases is still unclear., Objective: To understand the role of hyponatremia in falls, osteoporosis, fractures, and cognitive impairment in old patients., Method: Eligibility criteria for study inclusions were: written in English, peer-reviewed observational and intervention studies, clinical trial, prospective and retrospective controlled cohort studies, and case-controlled studies without limitations regarding the date of publication., Information Sources: Protocol available on the International Prospective Register of Systematic Reviews (PROSPERO, CRD42021218389). MEDLINE, Embase, and PsycINFO were searched. Final search done on August 8, 2021. Risk-of-bias assessment: Risk-of-Bias Assessment tool for Non-randomized Studies (RoBANS) and the Bradford Hill's criteria for causality., Results: Includes studies: One-hundred thirty-five articles retained for the revision. Synthesis of results - Falls: Eleven studies were included. Strong association between hyponatremia and falls in all the studies was found. Osteoporosis and fractures: nineteen articles were included. The association between hyponatremia and osteoporosis is unclear. Cognitive impairment: Five articles were included. No association between hyponatremia and cognitive impairment was found., Discussion: Interpretation: Falls, osteoporosis, and fractures are multifactorial. Hyponatremia is not temporally related with the outcomes; we suggest that hyponatremia may be regarded as a marker of unhealthy aging and a confounder instead of a causal factor or an innocent bystander for falls and fractures. Concerning cognitive impairment, there are no evidence supporting a real role of hyponatremia to be regarded as an innocent bystander in neurodegeneration., (© 2023. The Author(s).)

Objective: There is no consistent opinion on the optimal initial dose of desmopressin for patients with nocturnal polyuria. Over a period of 12 weeks, we investigated the safety and efficacy of an initial dose of 50 μg of desmopressin for elderly men., Methods: Eighty patients (mean age: 78.8 years) were started on an initial dose of 50 μg of desmopressin for nocturia associated with nocturnal polyuria. Safety and efficacy were evaluated after 1, 4, and 12 weeks using a frequency-volume chart, Athens Insomnia Scale, Patient Global Impression of Improvement scale, physical examination, blood tests, and a body composition analyzer., Results: Along with reduction in the frequency and volume of night-time urination, improvements in hours of undisturbed sleep, nocturnal polyuria index, and International Prostate Symptom Score, and Overactive Bladder Symptom Scores on quality of life measures were also observed. Hyponatremia was observed in 15 patients (18.7%). However, only 5.0% of patients had hyponatremia after the dose was reduced to 25 μg, and the continuation rate at 12 weeks was high at 87.5%. Age and other physical factors, such as body mass index, body water content, body fat mass, and muscle mass were not significant predictors of adverse events., Conclusions: Our study suggests that an initial dose of 50 μg is more effective than a uniformly minimum dose based on factors such as age and physique. Furthermore, a high continuation rate can be achieved by appropriately reducing the dose, if adverse events occur., (© 2023 John Wiley & Sons Australia, Ltd.)

Background: Disturbances in serum sodium concentration (dysnatremia) are common following aneurysmal subarachnoid hemorrhage (aSAH), but its direct impact on outcomes is not well understood. This study aimed to examine the association between dysnatremia following aSAH and patient outcomes., Methods: A retrospective cohort study of consecutive patients with aSAH who were admitted to an academic referral center between 2015 and 2021 was performed. Multivariate logistic regression was used to test the association of dysnatremia and outcomes including modified Rankin Scale score at 3 months after discharge and vasospasm. Multiple linear regression was used to test the association of hospital length of stay and dysnatremia., Results: We included 320 patients with confirmed aneurysmal etiology (mean [SD] age = 57.8 [14.3] years; 61% female; 70% White). No independent associations were found between hyponatremia or hypernatremia and functional outcome or vasospasm. However, hospital length of stay was longer in patients with hypernatremia (7 more days; 95% confidence interval = 4.4-9.6, P < 0.001) independent of age, Hunt and Hess grade, modified Fisher score, delayed cerebral ischemia, and other hospital complications., Conclusions: Although dysnatremia may not directly impact functional outcome or vasospasm risk, hypernatremia may prolong hospital length of stay. Judicious use of hypertonic saline solutions and avoidance of unnecessary dysnatremia in patients with aSAH should be considered., (Copyright © 2023 Elsevier Inc. All rights reserved.)