Investigation and management of hypotonic polyura is a common challenge in clinical endocrinology. The three main causes, recently renamed to arginine vasopressin deficiency (AVP-D, formerly central diabetes insipidus), AVP-resistance (AVP-R, formerly nephrogenic diabetes insipidus), and primary polydipsia (PP) require accurate diagnosis as management differs for each. This new nomenclature more accurately reflects pathophysiology, and has now been adopted by the Systemised Nomenclature of Medicine (SNOMED). Advances in diagnosis over the last few years have centered around the use of copeptin measurement. Here, we use three patient case histories to highlight the use of this approach, and to demonstrate how it can succeed where other approaches, such as the water deprivation test, sometimes fail. We discuss the overall approach to each type of patient and the strengths and limitations of diagnostic strategies, illustrating the use of the new nomenclature.

Vaginal drug delivery is often preferred over systemic delivery to reduce side effects and increase efficacy in treating diseases and conditions of the female reproductive tract (FRT). Current vaginal products have drawbacks, including spontaneous ejection of drug-eluting rings and unpleasant discharge from vaginal creams. Here, we describe the development and characterization of a hypotonic, gel-forming, Pluronic-based delivery system for vaginal drug administration. The rheological properties were characterized with and without common hydrogel polymers to demonstrate the versatility. Both qualitative and quantitative approaches were used to determine the Pluronic F127 concentration below the critical gel concentration (CGC) that was sufficient to achieve gelation when formulated to be hypotonic to the mouse vagina. The hypotonic, gel-forming formulation was found to form a thin, uniform gel layer along the vaginal epithelium in mice, in contrast to the rapidly forming conventional gelling formulation containing polymer above the CGC. When the hypotonic, gel-forming vehicle was formulated in combination with a progesterone nanosuspension (ProGel), equivalent efficacy was observed in the prevention of chemically-induced preterm birth (PTB) compared to commercial Crinone® vaginal cream. Further, ProGel showed marked benefits in reducing unpleasant discharge, reducing product-related toxicity, and improving compatibility with vaginal bacteria in vitro. A hypotonic, gel-forming delivery system may be a viable option for therapeutic delivery to the FRT.

OBJECTIVE: Hyponatremia is the most common electrolyte abnormality encountered in a hospital setting, and the data regarding the contribution of hyponatremia to overall mortality are conflicting. The study objective was to determine patients\' clinical profiles and outcomes with hyponatremia.
METHODS:  This prospective cross-sectional study was conducted at Dayanand Medical College and Hospital, Ludhiana, and included 375 adult patients aged more than 18 years with a confirmed diagnosis of hyponatremia. Patients were subdivided into three groups based on the severity of hyponatremia: mild (130-135 mmol/L), moderate (125-129 mmol/L), and profound (<125 mmol/L).
RESULTS: The most common symptom was confusion (57.3%) followed by deep somnolence (40%) and nausea (36.8%). The most common cause of hyponatremia was diuretics (30.7%), followed by the syndrome of inappropriate antidiuretic hormone secretion (SIADH) (17.8%) and chronic liver disease (CLD) (14.1%). The severity of hyponatremia did not significantly influence the outcome. Patients with CLD and chronic kidney disease (CKD) as the etiology of hyponatremia had significantly worse outcomes compared to other causes of hyponatremia. The most common type was hypovolemic hypotonic followed by euvolemic hypotonic and hypervolemia hypotonic hyponatremia. Nearly half of the total deaths were observed in the hypervolemic hyponatremia group and were significantly higher compared to the other two groups (p=0.001). Correction of hyponatremia (i.e., serum sodium >135 mmol/L) was significantly linked with good outcomes (p=0.003).
CONCLUSIONS: Our study showed that the etiology of hyponatremia was a more important prognostic indicator rather than the severity of hyponatremia. Normalization of serum sodium was associated with improved survival.

BACKGROUND: Iatrogenic hyponatremia is a common complication following intravenous maintenance fluid therapy (IV-MFT) in hospitalized children. Despite the American Academy of Pediatrics\' 2018 recommendations, IV-MFT prescribing practices still vary considerably.
OBJECTIVE: This meta-analysis aimed to compare the safety and efficacy of isotonic versus hypotonic IV-MFT in hospitalized children.
METHODS: We searched PubMed, Scopus, Web of Science, and Cochrane Central from inception to October 1, 2022.
METHODS: We included randomized controlled trials (RCTs) comparing isotonic versus hypotonic IV-MFT in hospitalized children, either with medical or surgical conditions. Our primary outcome was hyponatremia following IV-MFT. Secondary outcomes included hypernatremia, serum sodium, serum potassium, serum osmolarity, blood pH, blood sugar, serum creatinine, serum chloride, urinary sodium, length of hospital stay, and adverse outcomes.
METHODS: Random-effects models were used to pool the extracted data. We performed our analysis based on the duration of fluid administration (i.e., ≤ 24 and > 24 h). The Grades of Recommendations Assessment Development and Evaluation (GRADE) scale was used to evaluate the strength and level of evidence for recommendations.
RESULTS: A total of 33 RCTs, comprising 5049 patients were included. Isotonic IV-MFT significantly reduced the risk of mild hyponatremia at both ≤ 24 h (RR = 0.38, 95% CI [0.30, 0.48], P < 0.00001; high quality of evidence) and > 24 h (RR = 0.47, 95% CI [0.37, 0.62], P < 0.00001; high quality of evidence). This protective effect of isotonic fluid was maintained in most examined subgroups. Isotonic IV-MFT significantly increased the risk of hypernatremia in neonates (RR = 3.74, 95% CI [1.42, 9.85], P = 0.008). In addition, it significantly increased serum creatinine at ≤ 24 h (MD = 0.89, 95% CI [0.84, 0.94], P < 0.00001) and decreased blood pH (MD = -0.05, 95% CI [-0.08 to -0.02], P = 0.0006). Mean serum sodium, serum osmolarity, and serum chloride were lower in the hypotonic group at ≤ 24 h. The two fluids were comparable in terms of serum potassium, length of hospital stay, blood sugar, and the risk of adverse outcomes.
CONCLUSIONS: The main limitation of our study was the heterogeneity of the included studies.
CONCLUSIONS: Isotonic IV-MFT was superior to the hypotonic one in reducing the risk of iatrogenic hyponatremia in hospitalized children. However, it increases the risk of hypernatremia in neonates and may lead to renal dysfunction. Given that the risk of hypernatremia is not important even in the neonates, we propose to use balanced isotonic IV-MFT in hospitalized children as it is better tolerated by the kidneys than 0.9% saline.
UNASSIGNED: CRD42022372359. Graphical abstract A higher resolution version of the Graphical abstract is available as Supplementary information.

暂无摘要。

Hyponatraemia is a known complication in hospitalised children receiving maintenance intravenous fluid. Several studies have been published to investigate the efficacy and safety of intravenous fluids in children. However, there is still an ongoing debate regarding the ideal solution to be used in the paediatric population. Therefore, the aim of this meta-analysis was to investigate the safety and efficacy of administering isotonic versus hypotonic intravenous maintenance fluid in hospitalised children. An extensive search was undertaken on PubMed, Web of Science, Scopus, ScienceDirect, Google Scholar and Cochrane Library on 28 December 2020. Only randomised controlled trials (RCTs) were included. We used the random-effects model for all analyses. Risk ratio (RR) and mean difference with 95% confidence intervals (CIs) were used for dichotomous and continuous outcomes, respectively. The quality of each study was assessed using the Joanna Briggs Institute critical appraisal tool for RCTs. This study is registered with PROSPERO (CRD42021229067). Twenty-two RCTs with a total of 3795 participants were included. The studies encompassed surgical and medical patients admitted to intensive care unit as well as to general wards. We found that hypotonic fluid significantly increases the risk of hyponatremia at both ≤24 h (RR 0.34; 95% CI: 0.26-0.43, p < 0.00001) and >24 h (RR 0.48; 95% CI: 0.36-0.64, p < 0.00001). Isotonic fluid increases the risk of hypernatraemia at ≤24 h (RR 2.15; 95% CI: 1.24-3.73, p = 0.006). The prevalence of hyponatraemia was also higher in the hypotonic group at both ≤24 h (5.7% vs. 23.3%) and >24 h (6.0% vs. 26.3%). There was no statistically significant difference in the risk of developing adverse outcomes between the two groups. Mean serum and urine sodium as well as serum osmolality/osmolarity was lower in the hypotonic group. Isotonic solution is protective against the development of hyponatraemia while hypotonic solution increases the risk of hyponatraemia.

Continuous flow enteral fluid therapy with isotonic and hypotonic enteral electrolyte solutions are as safe and effective as intravenous fluid therapy. The aim of this study was to carry out a comparative assessment between continuous flow enteral and intravenous (IV) fluid therapy in adult experimentally dehydrated horses. Six experimentally dehydrated adult mares were used in a study carried out in a 6 × 3 crossover design, which each animal received three different treatments (isotonic enteral fluid therapy-EsISO, hypotonic enteral fluid therapy-EsHYPO and intravenous fluid therapy with Lactate Ringer Solution-LR IV, all in continuous flow). Solutions were administered at a rate of 15 mL-1.kg-1.h-1 for 8 h, after 36 h of water and food deprivation. Serum and urinary biochemical assessment; urinary volume, pH and specific gravity; and blood gas analysis were measured at -36, 0, 2, 4, 6, and 8 h. The dehydration period (DP) caused discrete hydroelectrolytic and acid base imbalances. The EsISO, EsHYPO and LR IV increased blood volume. Enteral solutions restored the imbalances yielded by the DP and all treatments increased urine volume. Also, the EsHYPO and LR IV showed no effects in acid base balance, while EsISO showed slightly acidifying effect. The present study certifies the efficacy and safety of isotonic and hypotonic continuous flow enteral fluid therapy in comparison to IV fluid therapy in dehydrated horses.

Congenital myopathies, such as nemaline myopathy, may present with hypotonia and respiratory failure in the neonatal period. Respiratory function can be further compromised in affected infants by the development of chylous effusions. We present the case of a preterm male infant born at 32 6/7 weeks\' gestation, who was profoundly hypotonic and required intubation at birth. His clinical course progressed from acute to chronic respiratory failure with mechanical ventilation dependence. He developed bilateral chylous pleural effusions during the newborn period. Whole exome sequencing identified an ACTA1 gene mutation leading to the presumed diagnosis of nemaline myopathy. This case highlights the need to include congenital myopathies in the differential for a preterm newborn with hypotonia and respiratory failure.

Persistent hypotonic and inflammatory conditions in the joint cavity can lead to the loss of cartilage matrix and cell death, which are the important mechanisms of osteoarthritis (OA) onset. Previous studies have confirmed that the existence of a hypotonic environment is a red flag for inflammation, as hypotonic environment induces the opening of the chloride channel of the cell and promotes chloride ion efflux, which prompts the cell volume to increase. Chloride channels play an important role in the regulation of mineralization and chondrocyte death. Here, we reported that OA chondrocytes showed a significant increase of cell death rate and the imbalance of cartilage matrix catabolism. We found that the distribution of skeleton protein F-actin was disordered. In addition, the volume-sensitive chloride current of OA chondrocytes decreased significantly with the increase of the expression levels of inflammation-related proteins caspase-1, caspase-3, and NLRP3. Moreover, interleukin-1β (IL-1β) showed a potential to activate the chloride current of normal chondrocytes. These results indicate that IL-1β-induced chloride channel opening in chondrocytes may be closely related to the occurrence of OA. This chloride channel opening process may therefore be a potential target for the treatment of OA.

OBJECTIVE: Hypotonic fluids have been traditionally used in newborns. National Institute for Health and Clinical Excellence-2015 (NICE) fluid therapy guideline recommends the use of isotonic fluids as maintenance fluid therapy in term newborns. However, there is no clear evidence supporting this recommendation. This study aims to compare isotonic (5% dextrose in 0.9% sodium chloride (NaCl)) and hypotonic (5% dextrose in 0.45% NaCl) parenteral fluid therapies in hospitalized term newborns with regard to changes in plasma Na (pNa) and complications related with fluid therapy.
METHODS: This was a retrospective cohort study performed in a tertiary university hospital NICU between January 2016 and April 2018. Term newborns who were initially isonatremic or mildly dysnatremic (pNa <130 or >155 meq/L) and receiving fluid therapy for maintenance or replacement therapy after 48th postnatal hours were eligible for the study. Infants having specific diagnoses requiring extraordinary fluids were excluded. The primary outcome evaluated was the change in mean plasma Na (ΔpNa meq/L/h) at 24 h or at the end of intravenous (i.v.) fluid therapy. Secondary outcomes evaluated were the risk of hyponatremia, hypernatremia, and adverse events attributable to fluid administration.
RESULTS: Among the 108 included newborns, 57 received hypotonic fluid (5% dextrose solution in 0.45% NaCl) and the remaining received isotonic fluid (5% dextrose solution in 0.9% NaCl) therapy. The hypotonic fluid group showed a greater ΔpNa compared to the isotonic group (0.48 ± 0.28 vs. 0.27 ± 0.21 meq/L/h, p = .001). The risk of experiencing unsafe plasma Na decrease in the hypotonic fluid group (ΔpNa >0.5 meq/L/h) was higher than the isotonic fluid group (odd ratio: 8.46; 95% confidence interval (CI): 2.3-30.06). Six mildly hypernatremic babies between 48 and 72 h of postnatal age showed insufficient Na reduction despite the appropriate amount of fluid. No significant difference was found between the two groups in terms of other outcomes.
CONCLUSIONS: The results of this study suggested that as maintenance or replacement fluid therapy in the newborn, hypotonic fluids, even 5% dextrose in 0.45% NaCl, can lead to unsafe plasma Na decreases in term newborns, while isotonic fluids are safe when started after the first few days of life. Although the results parallel NICE guidelines, before making recommendations regarding the removal of hypotonic fluids entirely from clinical practice in term newborns following the renal adaptation period; larger randomized controlled studies involving a wide range of babies are needed.