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Annals of Medicine and Surgery (2012) Aug 2023Osmotic demyelination syndrome (ODS) is a neurological disorder usually after rapid correction of hyponatremia. Only few cases of ODS with hypernatremia and diabetes...
UNLABELLED
Osmotic demyelination syndrome (ODS) is a neurological disorder usually after rapid correction of hyponatremia. Only few cases of ODS with hypernatremia and diabetes insipidus (DI) in postpartum state is reported. Postpartum hypernatremia is described as severe hypernatremia in postpartum period and presents as an encephalopathy with rhabdomyolysis with diffuse white matter hyperintensities suggestive of osmotic demyelination.
CASE PRESENTATION
The authors present a case of 29-year-old female who presented with chief complaint of altered sensorium and quadriparesis. Two days prior to onset of symptoms, she underwent caesarean section, was kept on nil per oral and free fluid restriction, after which she had confusion, altered sensorium, and weakness in all four limbs. Sodium level was 170 mEq/l. Urine osmolality and plasma osmolality was 150 and 410 mOsm/kg of water, respectively. MRI showed high signal intensity lesion in pons suggestive of demyelination. She was diagnosed ODS with transient DI and quadriparesis, in postpartum period due to further rise in sodium after free fluid restriction and nil per oral. She was treated with desmopressin, 5% dextrose and 0.9% normal saline, her quadriparesis recovered and desmopressin was tapered and stopped over 45 days and discharged at stable state.
CLINICAL DISCUSSION
ODS can rarely be associated with hypernatremia in postpartum female presenting as quadriparesis and altered sensorium.
CONCLUSION
Clinicians should be familiar of ODS with hypernatremia with transient DI in postpartum period, which is reversible and can be managed by desmopressin and fluid replacement.
PubMed: 37554876
DOI: 10.1097/MS9.0000000000000987 -
Journal of Thrombosis and Haemostasis :... Jul 2024In many patients referred with significant bleeding phenotype, laboratory testing fails to define any hemostatic abnormalities. Clinical practice with respect to... (Review)
Review
In many patients referred with significant bleeding phenotype, laboratory testing fails to define any hemostatic abnormalities. Clinical practice with respect to diagnosis and management of this patient cohort poses significant clinical challenges. We recommend that bleeding history in these patients should be objectively assessed using the International Society on Thrombosis and Haemostasis (ISTH) bleeding assessment tool. Patients with increased bleeding assessment tool scores should progress to hemostasis laboratory testing. To diagnose bleeding disorder of unknown cause (BDUC), normal complete blood count, prothrombin time, activated partial thromboplastin time, thrombin time, von Willebrand factor antigen, von Willebrand factor function, coagulation factors VIII, IX, and XI, and platelet light transmission aggregometry should be the minimum laboratory assessment. In some laboratories, additional specialized hemostasis testing may be performed to identify other rare causes of bleeding. We recommend that patients with a significant bleeding phenotype but normal laboratory investigations should be registered with a diagnosis of BDUC in preference to other terminology. Global hemostatic tests and markers of fibrinolysis demonstrate variable abnormalities, and their clinical significance remains uncertain. Targeted genomic sequencing examining candidate hemostatic genes has a low diagnostic yield. Underlying BDUC should be considered in patients with heavy menstrual bleeding since delays in diagnosis often extend to many years and negatively impact quality of life. Treatment options for BDUC patients include tranexamic acid, desmopressin, and platelet transfusions.
Topics: Humans; Hemostasis; Blood Coagulation Tests; Hemorrhage; Phenotype; Terminology as Topic; Blood Coagulation; Predictive Value of Tests; Hemorrhagic Disorders
PubMed: 38518896
DOI: 10.1016/j.jtha.2024.03.005 -
Endocrine Connections Dec 2023We aimed to describe and predict the risk of severe hypernatremia after surgical resection of craniopharyngioma and to identify the association of water intake, urine...
PURPOSE
We aimed to describe and predict the risk of severe hypernatremia after surgical resection of craniopharyngioma and to identify the association of water intake, urine output, and sodium level change in the patients.
METHOD
The outcome was postoperative severe hypernatremia. We identified risk factors associated with hypernatremia using multivariable regression. We trained machine learning models to predict the outcome. We compared serum sodium change, intravenous input, oral input, total input, urine output, and net fluid balance according to different nurse shifts.
RESULTS
Among 234 included patients, 125 developed severe hypernatremia after surgery. The peak incidence occurred during day 0 and day 6 after surgery. The risk was increased in patients with gross total resection (odds ratio (OR) 2.41, P < 0.001), high Puget classification (OR 4.44, P = 0.026), preoperative adrenal insufficiency (OR 2.01, P = 0.040), and preoperative hypernatremia (OR 5.55, P < 0.001). The random forest algorithm had the highest area under the receiver operating characteristic curve (0.770, 95% CI, 0.727-0.813) in predicting the outcome and was validated in the prospective validation cohort. Overnight shifts were associated with the highest serum sodium increase (P = 0.010), less intravenous input (P < 0.001), and less desmopressin use (P < 0.001).
CONCLUSION
The overall incidence of severe hypernatremia after surgical resection of craniopharyngioma was significant, especially in patients with gross total resection, hypothalamus distortion, preoperative adrenal insufficiency, and preoperative severe hypernatremia. Less intravenous input and less desmopressin use were associated with serum sodium increases, especially during overnight shifts.
PubMed: 37855388
DOI: 10.1530/EC-23-0149 -
Science Translational Medicine Sep 2023Biopharmaceuticals, including proteins and peptides, have revolutionized the treatment of a wide range of diseases, from diabetes and cardiovascular disorders to virus...
Biopharmaceuticals, including proteins and peptides, have revolutionized the treatment of a wide range of diseases, from diabetes and cardiovascular disorders to virus infections and cancer. Despite their efficacy, most of these macromolecular drugs require parenteral administration because of their high molecular weight and relative instability. Over the past 40 years, only a few oral peptide drugs have entered clinical trials, even when formulated with substantial amounts of permeation enhancers. To overcome the epithelial barrier, devices that inject drugs directly into the gastrointestinal mucosa have been proposed recently. However, the robustness and safety of those complex systems are yet to be assessed. In this study, we introduced an innovative technology to boost drug absorption by synergistically combining noninvasive stretching of the buccal mucosa with permeation enhancers. Inspired by the unique structural features of octopus suckers, a self-applicable suction patch was engineered, enabling strong adhesion to and effective mechanical deformation of the mucosal tissue. In dogs, this suction patch achieved bioavailability up to two orders of magnitude higher than those of the commercial tablet formulation of desmopressin, a peptide drug known for its poor oral absorption. Moreover, systemic exposure comparable to that of the approved oral semaglutide tablet was achieved without further optimization. Last, a first-in-human study involving 40 healthy participants confirmed the dosage form's acceptability, thereby supporting the clinical translatability of this simple yet effective platform technology.
Topics: Humans; Animals; Dogs; Drug Delivery Systems; Administration, Buccal; Peptides; Mouth Mucosa; Absorption, Physiological; Tablets; Administration, Oral
PubMed: 37756378
DOI: 10.1126/scitranslmed.abq1887 -
Cureus Aug 2023Von Willebrand disease (VWD) and hemophilia A are the most common inherited bleeding disorders. Quantitative or qualitative von Willebrand factor (VWF) anomalies cause... (Review)
Review
Von Willebrand disease (VWD) and hemophilia A are the most common inherited bleeding disorders. Quantitative or qualitative von Willebrand factor (VWF) anomalies cause this disorder in men and women. VWF, a plasma glycoprotein, relies on platelets for primary hemostasis. It also carries and stabilizes factor VIII in the blood. VWD has several categories. Types 1 and 3 have partial or total VWF quantitative deficiencies. However, type 2 and its subtypes have VWF quality issues. The major treatment is desmopressin (DDAVP), which replaces endogenous VWF and factor VIII (FVIII). Plasma-derived VWF/FVIII products may also be substituted exogenously. Treatment with plasma-derived or recombinant VWF concentrates without FVIII is also possible. The purpose of this retrospective, single-center research was to evaluate DDAVP's efficacy in treating VWD based on many criteria established in the current literature. We looked at the results on Google Scholar, the Cochrane Library, and PubMed/Medline. There were a total of 10 papers found, evaluated, and accepted for inclusion in this study. A comprehensive analysis of DDVAP's role in VWD was compiled from the aforementioned papers. Various aspects of DDVAP were captured by including an analysis of complementary treatments used in surgical and clinical settings. We also describe the treatment's intended impact on the different variations of the disease. Given these results, further investigation is required to determine the most effective method for managing VWD so that it may be included in standard clinical practice.
PubMed: 37649925
DOI: 10.7759/cureus.44310 -
Neurourology and Urodynamics Jan 2024This pooled analysis aims to demonstrate the clinical efficacy and safety of combined desmopressin and anticholinergic therapy in the treatment of pediatric nocturnal... (Review)
Review
OBJECTIVE
This pooled analysis aims to demonstrate the clinical efficacy and safety of combined desmopressin and anticholinergic therapy in the treatment of pediatric nocturnal enuresis (NE).
METHODS
A systematic search was conducted through PubMed, MEDLINE, EMBASE, ResearchGate, and Cochrane Library to identify all randomized controlled trials (RCTs) comparing monotherapy with desmopressin versus combined therapy with desmopressin and anticholinergic agents for the treatment of NE. Data analysis was performed using RevMan version 5.4.1.
RESULTS
This study included 8 RCTs involving a total of 659 patients. The frequencies of complete response (CR), partial response (PR), and nonresponse (NR) were computed for both short-term treatment (1 month) and long-term treatment (3 months). Additionally, alterations in the mean number of NE episodes, adverse events, and relapse were assessed. Our analysis indicates that, in comparison to the monotherapy group, the combination therapy group plays a pivotal role in augmenting the CR odds and diminishing the NR ratios in both short-term and long-term treatments (1 month CR ratio [risk ratio (RR): 1.84; 95% confidence interval (CI): 1.22-2.76; p = 0.003, I = 72%]; 3 months CR ratio [RR: 1.48; 95% CI: 1.25-1.76; p < 0.00001, I = 0%]; 1 month NR ratio [RR: 0.67; 95% CI: 0.55-0.82; p = 0.0001, I = 0%]; 3 months CR ratio [RR: 0.37; 95% CI: 0.19-0.73; p = 0.004, I = 0%]). Furthermore, in both short-term and long-term treatment, the combined therapy group exhibits a greater magnitude of change in the average number of NE episodes compared to patients receiving monotherapy (1 month, mean difference [MD] = -2.97; 95% CI: -4.23 to -1.71, p < 0.0001; 3 months, MD = -4.30; 95% CI: -7.18 to -1.43, p = 0.003). Moreover, the combination therapy group exhibits a significant reduction in the recurrence rate (RR: 0.36; 95% CI: 0.15-0.86; p = 0.02). There is no significant difference in the incidence of adverse events between the two groups (RR: 1.16; 95% CI: 0.58-2.31; p = 0.67).
CONCLUSION
Combining desmopressin with anticholinergic medications is more effective for NE than desmopressin alone, with lower recurrence and minimal adverse effects.
Topics: Child; Humans; Cholinergic Antagonists; Combined Modality Therapy; Deamino Arginine Vasopressin; Drug Therapy, Combination; Nocturnal Enuresis; Pathologic Complete Response
PubMed: 37787540
DOI: 10.1002/nau.25295 -
Pediatric Nephrology (Berlin, Germany) Oct 2023Nocturnal enuresis (NE) is a common disease with multiple pathogenic mechanisms. This study aimed to compare levels of metabolites and proteins between wet and dry...
BACKGROUND
Nocturnal enuresis (NE) is a common disease with multiple pathogenic mechanisms. This study aimed to compare levels of metabolites and proteins between wet and dry nights in urine samples from children with monosymptomatic NE (MNE).
METHODS
Ten boys with MNE and nocturnal polyuria (age: 7.6 ± 1.3 years) collected their total nighttime urine production during a wet and a dry night. Untargeted metabolomics and proteomics were performed on the urine samples by liquid chromatography coupled with high-mass accuracy tandem mass spectrometry (LC-MS/MS).
RESULTS
On wet nights, we found reduced urine osmolality (P = 0.025) and increased excretion of urinary potassium and sodium by a factor of, respectively, 2.1 (P = 0.038) and 1.9 (P = 0.19) compared with dry nights. LC-MS identified 59 metabolites and 84 proteins with significantly different levels between wet and dry nights (fold change (FC) < 0.67 or > 1.5, P < 0.05). Some compounds were validated by different methodologies. During wet nights, levels of compounds related to oxidative stress and blood pressure, including adrenalin, were increased. We found reduced levels of aquaporin-2 on wet nights. The FCs in the 59 metabolites were positively correlated to the FCs in the same metabolites identified in urine samples obtained during the evening preceding wet and dry nights.
CONCLUSIONS
Oxidative stress, which in the literature has been associated with nocturia and disturbances in sleep, might be increased during wet nights in children with MNE. We further found evidence of increased sympathetic activity. The mechanisms related to having wet nights in children with MNE seem complex, and both free water and solute handling appear to be important. A higher resolution version of the Graphical abstract is available as Supplementary information.
Topics: Male; Humans; Child; Nocturnal Enuresis; Polyuria; Proteome; Nocturia; Chromatography, Liquid; Tandem Mass Spectrometry; Metabolome; Deamino Arginine Vasopressin
PubMed: 37140712
DOI: 10.1007/s00467-023-05963-5 -
Neurourology and Urodynamics Nov 2023The link between nocturia and cardiovascular disease (CVD) is frequently discussed in literature, yet the precise nature of this relationship remains poorly... (Review)
Review
AIMS
The link between nocturia and cardiovascular disease (CVD) is frequently discussed in literature, yet the precise nature of this relationship remains poorly characterized. The existing literature was reviewed in order to address issues concerning the origin, diagnosis, management, and implications of the co-occurrence of CVD and nocturia.
METHODS
This review summarizes literature and recommendations regarding the link between CVD and nocturia discussed during a think-tank meeting held at the 2023 International Consultation on Incontinence-Research Society.
RESULTS
Cardiovascular disorders are often underestimated contributors to nocturia, with various potential mechanisms influencing nighttime urination, such as impact on fluid retention, atrial natriuretic peptide, and glomerular filtration rate. The redistribution of fluid from leg edema in supine position can lead nocturnal polyuria (NP). Additionally, sleep disturbances due to nocturia in itself may lead to CVD through an increase in blood pressure, insulin resistance, and inflammation. Disrupted circadian rhythms (e.g., in sleep pattern and urine production) were identified as critical factors in most etiologies of nocturia, and their contribution is deemed imperative in future research and treatment approaches, particularly in the aging population. NP can be detected through a simple bladder diary and can even be used to distinguish cardiac from noncardiac causes of nocturia. For the treatment of NP, desmopressin can be effective in select patients, however, caution and close monitoring is warranted for those with CVD due to increased risk of side effects.
CONCLUSIONS
Gaps were identified in the available evidence and clear cut recommendations were put forth for future research. It is essential to gain a deeper understanding of the mechanisms linking nocturia and CVD to develop optimal management strategies.
PubMed: 37942826
DOI: 10.1002/nau.25331 -
The Journal of Physiology Dec 2023Aquaporin-2 (AQP2) water channels are proteins that are recycled between intracellular vesicles and the apical plasma membrane in renal collecting ducts....
Aquaporin-2 (AQP2) water channels are proteins that are recycled between intracellular vesicles and the apical plasma membrane in renal collecting ducts. Lipopolysaccharide-responsive beige-like anchor protein (LRBA) is a protein kinase A (PKA) anchoring protein that creates compartmentalized PKA signalling responsible for AQP2 phosphorylation. In response to increased plasma osmolality, vasopressin/cyclic adenosine monophosphate (cAMP)/PKA signalling phosphorylates AQP2, promoting AQP2 trafficking into the apical plasma membrane and increasing water reabsorption from urine. However, the molecular mechanisms by which LRBA mediates vasopressin-induced AQP2 phosphorylation remain unknown. To investigate AQP2 intracellular localization and phosphorylation status in vivo, a density gradient ultracentrifugation technique was combined with an in situ proximity ligation assay, super-resolution structured illumination microscopy and immunoelectron microscopy. Most of the AQP2 was localized on the recycling endosome in the presence of tolvaptan, a vasopressin type 2 receptor (V2R) antagonist. Desmopressin, a V2R agonist, phosphorylated AQP2, translocating it from the recycling endosome to the apical plasma membrane. In contrast, LRBA was constitutively localized at the recycling endosome. Therefore, LRBA and AQP2 were well colocalized in the absence of vasopressin stimulation. The loss of LRBA/PKA signalling by Lrba knockout impaired vasopressin-induced AQP2 phosphorylation, resulting in AQP2 retention at the recycling endosome. Defective AQP2 trafficking caused low urinary concentrating ability in Lrba mice. The LRBA-PKA complex created compartmentalized PKA signalling at the recycling endosome, which facilitated AQP2 phosphorylation in response to vasopressin. KEY POINTS: Membrane proteins are continuously internalized into the endosomal system via endocytosis, after which they are either recycled back to the plasma membrane or degraded at the lysosome. In T cells, lipopolysaccharide-responsive beige-like anchor protein (LRBA) binds directly to the cytotoxic T lymphocyte antigen 4 (CTLA-4), a checkpoint immune molecule, to prevent CTLA-4 lysosomal degradation and promote its vesicle recycling. LRBA has different physiological functions in renal collecting ducts. LRBA and aquaporin-2 (AQP2) water channels were colocalized on the recycling endosome in vivo in the absence of the anti-diuretic hormone vasopressin. LRBA promoted vasopressin-induced AQP2 trafficking, increasing water reabsorption from urine via AQP2. LRBA determined renal responsiveness to vasopressin at recycling endosomes. LRBA is a ubiquitously expressed anchor protein. LRBA signalosomes might regulate membrane trafficking of several constitutively recycled proteins at recycling endosomes.
Topics: Mice; Animals; Aquaporin 2; CTLA-4 Antigen; Lipopolysaccharides; Protein Transport; Vasopressins; Endosomes; Antidiuretic Hormone Receptor Antagonists; Cyclic AMP-Dependent Protein Kinases; Water; Phosphorylation; Kidney Tubules, Collecting
PubMed: 37860942
DOI: 10.1113/JP285188