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Background Glucocorticoids are used for a variety of purposes in veterinary medicine but often are associated with clinically important adverse effects. Polyuria and polydipsia are the most frustrating adverse effects noted by owners. Objective To determine whether administration of desmopressin ameliorates polyuria and polydipsia associated with prednisolone administration. Animals Seven healthy adult Walker Hounds. Methods Prospective hypothesis testing study. Daily water intake and urine specific gravity (USG) were measured in dogs under 4 separate sequential conditions: no medications (C), prednisolone only (P), prednisolone and desmopressin (PD), and prednisolone after discontinuation of desmopressin (PAD). Results When compared to baseline, 6 of 7 dogs became polydipsic after administration of prednisolone (0.5 mg/kg PO q12h). When desmopressin (5 μg/dog SC q12h) was administered to dogs receiving prednisolone, significant decreases in water intake and serum sodium concentration occurred, and USG increased significantly. Conclusions and Clinical Importance Administration of desmopressin to dogs receiving prednisolone significantly decreased water intake and serum sodium concentration, and increased USG. Our results suggest that, in some dogs, desmopressin ameliorates the most important adverse effect of prednisolone noted by owners, but that hyponatremia is an important complication associated with desmopressin use.

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Urinary uromodulin, secreted by renal tubular cells, protects against urinary tract infections and kidney stones. In contrast, the intracellular accumulation of uromodulin is associated with hypertension and chronic kidney disease. However, the physiological stimuli for urinary uromodulin secretion remain largely unknown. Here, we showed that desmopressin, a vasopressin type 2 receptor agonist, dramatically increased short-term tubular uromodulin secretion in mice. Immunofluorescence studies and ultracentrifugation-based polymerization assay suggested that desmopressin induced intraluminal polymeric filaments of uromodulin, indicating physiologically functional secretion. As a result of increased excretion, uromodulin abundance in the murine kidney was clearly reduced by desmopressin. We investigated kidney epithelial cells stably expressing uromodulin to clarify the molecular mechanism. Apical uromodulin secretion was clearly increased in response to vasopressin/cAMP signaling, consistent with in vivo experiments. We also demonstrated that the response was dependent on epithelial cell polarity and cyclic AMP-dependent PKA (protein kinase A) signaling pathway. cAMP-mediated activation of proteases was suggested to be involved. In contrast, basolateral secretion of uromodulin was independent of cAMP signaling. Our work revealed vasopressin/cAMP/PKA signaling as a physiological stimulus of urinary uromodulin secretion. This finding may provide the basis for novel treatment strategies for urinary tract infections, kidney stones, and potentially hypertension and chronic kidney disease.

There is inconsistency in the amount of oral desmopressin that children with central diabetes insipidus require. We investigated whether clinical characteristics influenced desmopressin dose requirements in 100 children with central diabetes insipidus. Extremely large doses were associated with acquired etiology (P = .04), greater body mass index z score, intact thirst, and additional pituitary hormone deficiencies (P .001).

Background\ud \ud Central diabetes insipidus is a rare neuroendocrine condition. Data on treatment-associated side-effects, psychological comorbidities, and incorrect management are scarce. The aim of this study was to investigate patients’ perspectives on their disease.\ud \ud \ud \ud Methods\ud \ud This study used a cross-sectional, web-based, anonymous survey, developed by endocrinologists and patient representatives, to collect the opinions of patients with central diabetes insipidus on management and complications of their disease, psychological comorbidities, degree of knowledge and awareness of the condition among health-care professionals, and renaming the disease to avoid confusion with diabetes mellitus (diabetes).\ud \ud \ud \ud Findings\ud \ud Between Aug 23, 2021, and Feb 7, 2022, 1034 patients with central diabetes insipidus participated in the survey. 91 (9%) participants were children and adolescents (37 [41%] girls and 54 [59%] boys; median age 10 years [IQR 6–15]) and 943 (91%) were adults (757 [80%] women and 186 [20%] men]; median age 44 years [34–54]). 488 (47%) participants had isolated posterior pituitary dysfunction and 546 (53%) had combined anterior and posterior pituitary dysfunction. Main aetiologies were idiopathic (315 [30%] of 1034 participants) and tumours and cysts (pre-surgical 217 [21%]; post-surgical 254 [25%]). 260 (26%; 95% CI [0·23–0·29]) of 994 patients on desmopressin therapy had hyponatraemia leading to hospitalisation. Patients who routinely omitted or delayed desmopressin to allow intermittent aquaresis had a significantly lower prevalence of hyponatraemia compared with those not aware of this approach (odds ratio 0·55 [95% CI 0·39–0·77]; p=0·0006). Of patients who had to be hospitalised for any medical reason, 71 (13%; 95% CI 0·10–0·16) of 535 patients did not receive desmopressin while in a fasting state (nil by mouth) without intravenous fluid replacement and reported symptoms of dehydration. 660 (64%; 0·61–0·67) participants reported lower quality of life, and 369 (36%; 0·33–0·39) had psychological changes subjectively associated with their central diabetes insipidus. 823 (80%; 0·77–0·82) participants encountered a situation where central diabetes insipidus was confused with diabetes mellitus (diabetes) by health-care professionals. 884 (85%; 0·83–0·88) participants supported renaming the disease; the most favoured alternative names were vasopressin deficiency and arginine vasopressin deficiency.\ud \ud \ud \ud Interpretation\ud \ud This is the largest survey of patients with central diabetes insipidus, reporting a high prevalence of treatment-associated side-effects, mismanagement during hospitalisation, psychological comorbidities, and a clear support for renaming the disease. Our data are the first to indicate the value of routinely omitting or delaying desmopressin.\ud \ud \ud \ud Funding\ud \ud Swiss National Science Foundation, Swiss Academy of Medical Sciences, and G&J Bangerter-Rhyner-Foundation.

Purpose To determine the association between urine osmolality (Uosm) in patients with primary monosymptomatic enuresis (PMNE) and response to desmopressin (dDAVP) lyophilisate. Methods This was a prospective cohort study that included 419 children with enuresis seen in outpatient clinic between October 2017 and October 2019. Patient workup included symptom checklist, 48 h frequency/volume chart, kidney and bladder ultrasound, uroflow, urinalysis and culture, spot urine Ca/creatinine, and first-morning Uosm. Patients < 5 years, with secondary enuresis, or loss of follow-up were excluded. Oral dDAVP lyophilisate was recommended to all with PMNE and normal bladder capacity. After 1 month of therapy, initial success was assessed according to ICCS. Significant predictor variables for complete response were identified and analyzed using correlation coefficients and binary logistic regression. Results There were 48 patients with PMNE who received dDAVP and were followed for treatment success. Partial and complete responses were achieved for 14 (29.2%) and 20 cases (41.7%), respectively. Older age and lower Uosm were found to be significantly in favor of complete response to dDAVP lyophilisate, P = 0.007 and 0.033, respectively. ROC analysis determined the Uosm of 814 mOsm/kg) might be suggestive of an alternative treatment to dDAVP lyophilisate in PMNE because of the higher risk of treatment failure.

Background: Nocturnal enuresis is a common disease of childhood. It can be classified into monosymptomatic nocturnal enuresis (MNE) or nonmonosymptomatic nocturnal enuresis (NMNE). Imipramine is a tricyclic antidepressant used to treat enuresis with initial success rates are high as 50% but some studies record a high relapse rate and it has a cardiotoxic effect when overdosed. Anticholinergics may be effective in the treatment of children with bladder storage dysfunction, including daytime incontinence. However, anticholinergics monotherapy is not effective in treating MNE. In our study, we used a low dose (25 mg) of imipramine in order to avoid its potential side effects and combined it with the synergistic anticholinergic action of solifenacin. Our objective was to evaluate the efficacy and safety of the combination of solifenacin and imipramine compared with placebo in the treatment of desmopressin refractory MNE. Methods: One hundred children aged 6 years or more with primary MNE unresponsive to desmopressin treatment were included. The children were randomly divided into two equal groups. Group A received imipramine 25 mg and solifenacin 5–10 mg oral tablets and group B received placebo once 1 h before bedtime for 3 months. The primary end point was to investigate the efficacy of the combined treatment of solifenacin and imipramine and the secondary end point was the safety of the drugs. Results: Our study showed that the mean post treatment wet nights per month was significantly lesser in the treatment group than placebo group ( p Conclusion: The combination treatment of solifenacin and imipramine is a useful and safe treatment for nocturnal enuresis after failure of everything else.

Bilateral inferior petrosal sinus sampling (BIPSS) is the current gold standard test for differentially diagnosing ACTH-dependent Cushing's syndrome (CS). However, BIPSS is an invasive procedure, and its availability is limited. We retrospectively analysed the 24-hour urinary free cortisol (UFC) level during the high-dose dexamethasone suppression test (HDDST) and plasma ACTH/cortisol levels after the desmopressin stimulation test (DDAVP test) in subjects with confirmed Cushing's disease (CD) (n = 92) and ectopic ACTH-dependent CS (EAS) (n = 16), and evaluated the positive predictive value (PPV) of the two combined-tests in the aetiological diagnosis of ACTH-dependent CS. The percent changes in UFC levels after the HDDST and in ACTH/cortisol levels after DDAVP administration relative to the corresponding basal levels and the area under the receiver operating characteristic (ROC) curve (AUC) were analysed. UFC suppression below 62.7% suggested a pituitary origin with a sensitivity (SE) of 80% (95% CI: 70-88) and a specificity (SP) of 80% (95% CI: 52-96). A threshold increase in the ACTH level after DDAVP stimulation of 44.6% identified CD with an SE of 91% (95% CI: 83-97) and an SP of 75% (95% CI: 48-93). The combination of both tests yielded an SE of 95.5% and PPV of 98.4% for CD, and significantly improved the efficiency of the differential diagnosis between CD and EAS. These dual non-invasive endocrine tests may substantially reduce the need for BIPSS in the etiological investigation of ACTH-dependent CS.

Initiation of desmopressin acetate (DDAVP) for untreated diabetes insipidus (DI) in Wolfram syndrome (WS) causes abrupt volume expansion resulting in particularly high secretion of Atrial Natriuretic Peptide (ANP) and/or Brain Natriuretic Peptide (BNP), which in turn blocks all stimulators of zona glomerulosa steroidogenesis, resulting in secondary mineralocorticoid deficiency and acute hyponatremia, causing renal salt wasting (RSW). Two sisters, a 19-y-old girl (A) and a 7-y-old girl (B) with WS, presented with severe polyuria-polydipsia due to never treated DI. Both had neurogenic bladder and "B" had severe hydronephrosis secondary to untreated grade III bilateral vesicoureteral reflux. They initiated therapy with oral melt DDAVP which resulted in RSW. ANP was found ×50 and BNP ×2-4 fold elevated. Fludrocortisone 100-200 × 2 μg/d controlled natriuresis and restored electrolytes to normal within 48 h. Fludrocortisone treatment rescues otherwise potentially life-threatening hyponatremia due to RSW and the secondary mineralocorticoid deficiency driven by elevated ANP and/or BNP, caused by sudden volume expansion following DDAVP initiation.

We herein report a rare case of advanced lung adenocarcinoma with central diabetes insipidus due to pituitary metastasis. Although treatment with gefitinib was dramatically effective, the symptoms of diabetes insipidus did not improve. Radiotherapy for pituitary metastasis was effective to control diabetes insipidus; however, we could not cease the administration of 1-deamino-8-D-arginine vasopressin (DDAVP). It is important for physicians to positively consider radiotherapy for pituitary metastases even if favorable tumor control is achieved with chemotherapy when diabetes insipidus becomes clinically overt. Furthermore, continuous DDAVP administration may be needed to treat central diabetes insipidus.

Objective Most von Willebrand disease (VWD) patients can be treated with desmopressin during bleeding or surgery. Large interpatient variability is observed in von Willebrand factor (VWF) activity levels after desmopressin administration. The aim of this study was to develop a pharmacokinetic (PK) model to describe, quantify, and explain this variability. Methods Patients with either VWD or low VWF, receiving an intravenous desmopressin test dose of 0.3 µg kg−1, were included. A PK model was derived on the basis of the individual time profiles of VWF activity. Since no VWF was administered, the VWF dose was arbitrarily set to unity. Interpatient variability in bioavailability (F), volume of distribution (V), and clearance (Cl) was estimated. Results The PK model was developed using 951 VWF activity level measurements from 207 patients diagnosed with a VWD type. Median age was 28 years (range: 5–76), median predose VWF activity was 0.37 IU/mL (range: 0.06–1.13), and median VWF activity response at peak level was 0.64 IU/mL (range: 0.04–4.04). The observed PK profiles were best described using a one-compartment model with allometric scaling. While F increased with age, Cl was dependent on VWD type and sex. Inclusion resulted in a drop in interpatient variability in F and Cl of 81.7 to 60.5% and 92.8 to 76.5%, respectively. Conclusion A PK model was developed, describing VWF activity versus time profile after desmopressin administration in patients with VWD or low VWF. Interpatient variability in response was quantified and partially explained. This model is a starting point toward more accurate prediction of desmopressin dosing effects in VWD.

Introduction Central diabetes insipidus is a heterogeneous condition characterized by decreased release of antidiuretic hormone by the neurohypophysis resulting in a urine concentration deficit with variable degrees of polyuria. The most common causes include idiopathic diabetes insipidus, tumors or infiltrative diseases, neurosurgery and trauma. Temozolomide is an oral DNA-alkylating agent capable of crossing the blood-brain barrier and used as chemotherapy primarily to treat glioblastoma and other brain cancers. Cases Two men (aged 38 and 54 years) suddenly developed polyuria and polydispsia approximately four weeks after the initiation of temozolomide for a glioblastoma. Plasma and urine parameters demonstrated the presence of a urinary concentration defect. Management The clinical and laboratory abnormalities completely resolved with intranasal desmopressin therapy, allowing the continuation of temozolomide. The disorder did not relapse after cessation of temozolomide and desmopressin and relapsed in one patient after rechallenge with temozolomide. Discussion Our report highlights the importance of a quick recognition of this exceptional complication, in order to initiate promptly treatment with desmopressin and to maintain therapy with temozolomide.

Objectives To investigate the long-term efficacy, quality of life (QoL), and safety of desmopressin orally disintegrating tablets (ODTs) in Japanese patients with nocturia. Methods A long-term, multicenter phase 3 study was conducted that enrolled Japanese male and female patients with nocturia (NCT03051009). Male patients received desmopressin 25- or 50-μg ODTs, and female patients received desmopressin 25-μg ODTs for up to 1 year. The primary endpoint was safety. Secondary endpoints included change from baseline in number of nocturnal voids, time to first awakening to void, and QoL assessments (nocturia-specific zQoL [N-QoL], Insomnia Severity Index [ISI], and Hsu bother score). Results Overall, 503 patients were enrolled. Reductions from baseline in mean number of nocturnal voids were observed in all treatment groups from week 1 (-0.62 to -1.00), with improvements continuing through week 52 (-1.39 to -1.71). Changes from baseline above or approximating a clinically meaningful improvement were seen by week 52 in the disease-specific N-QoL total score (improved by 11.5-22.6), ISI (improved by -3.9 to -7.1), and Hsu bother scores (improved by -1.5 to -2.0). Adverse events (AEs) were reported in 54.9% of desmopressin-treated patients. Most AEs were mild or moderate in severity. Conclusions Desmopressin ODTs (25 and 50 μg) demonstrated long-term efficacy, improved QoL, and were well tolerated in Japanese male and female patients with nocturia treated for up to 1 year. Clinically meaningful improvements in patients' QoL, assessed by N-QoL, sleep quality, and bother, occur later than objective symptom improvements, such as voids.

Background Patients with type 1 von Willebrand disease (VWD) undergo a desmopressin (DDAVP) responsiveness challenge at diagnosis to assess whether DDAVP reverses their coagulation deficits. Current practice assumes DDAVP responsiveness remains constant over the lifetime. In patients with type 1 VWD, VWF‐related parameters increase with age. This study explores whether DDAVP responsiveness also differs with age in this population. Methods We conducted a retrospective chart review of 106 patients enrolled at our center since 1990. Our primary outcome was DDAVP responsiveness at 1 hour after DDAVP challenge. Locally weighted scatterplot smoothing fit and Spearman correlation coefficients were used to study the relationship between age and DDAVP responsiveness. For female participants, we used the Kruskal‐Wallis test to compare absolute and relative changes in DDAVP responsiveness at various ages. Results We had 79 patients (56 female) with type 1 VWD with at least 1 DDAVP challenge. In women with type 1 VWD, the absolute change in DDAVP responsiveness did not vary significantly with age (VWF:antigen [Ag], −0.08, P = .56; VWF:ristocetin cofactor [RCo], −0.16, P = .26; low‐molecular‐weight component of factor VIII [FVIII:C], −0.01, P = .93), nor did the relative change in DDAVP responsiveness (VWF:Ag, −0.03, P = .86; VWF:RCo, −0.25, P = .09; FVIII:C, −0.14, P = .34). The data plot suggested a relationship. Conclusion In women with type 1 VWD, DDAVP responsiveness may vary over the life cycle. Our exploratory findings are limited by our retrospective data, cross‐sectional design, and small sample. Future studies should investigate the relationship between age and DDAVP responsiveness prospectively to evaluate whether there is clinical utility in rechallenging postpubertal female patients with type 1 VWD.

Background The most profound effect of vasopressin on the kidney is to increase water reabsorption through V2-receptor (V2R) stimulation, but there are also data suggesting effects on calcium transport. To address this issue, we have established an isolated perfused kidney model with accurate pressure control, to directly study the effects of V2R stimulation on kidney function, isolated from systemic effects. Methods The role of V2R in renal calcium handling was studied in isolated rat kidneys using a new pressure control system that uses a calibration curve to compensate for the internal pressure drop up to the tip of the perfusion cannula. Results Kidneys subjected to V2R stimulation using desmopressin (DDAVP) displayed stable osmolality and calcium reabsorption throughout the experiment, whereas kidneys not administered DDAVP exhibited a simultaneous fall in urine osmolality and calcium reabsorption. Epithelial sodium channel (ENaC) inhibition using amiloride resulted in a marked increase in potassium reabsorption along with decreased sodium reabsorption. Conclusions A stable isolated perfused kidney model with computer-controlled pressure regulation was developed, which retained key physiological functions. The preparation responds to pharmacological inhibition of ENaC channels and activation of V2R. Using the model, the dynamic effects of V2R stimulation on calcium handling and urine osmolality could be visualised. The study thereby provides evidence for a stimulatory role of V2R in renal calcium reabsorption.

Osteoprotegerin (OPG) regulates bone metabolism by reducing the activation of osteoclasts, but may also be involved in blood vessel calcification and atherosclerosis. Within endothelial cells OPG is stored in Weibel–Palade bodies (WPBs). Blood kinetics of OPG are essentially unknown. We aimed to assess these using two distinct in vivo models; one after stimulation with desmopressin (DDAVP) and another after stimulation with lipopolysaccharide (LPS). Both clinical trials were conducted at the Department of Clinical Pharmacology at the Medical University of Vienna, Austria. Participants received desmopressin (0.3 µg/kg), LPS (2 ng/kg), or placebo (sodium chloride 0.9%) with subsequent blood sampling at time points up to 24 hours after administration. The primary objective of this study was to investigate the plasma kinetics of OPG after stimulation with desmopressin and LPS. Secondary analyses included the release of other WPB contents including von Willebrand factor (vWF). This analysis included 31 healthy volunteers (n = 16 for desmopressin and placebo, n = 15 for LPS). Infusion of desmopressin did not increase OPG concentrations compared with placebo, while LPS infusion significantly increased OPG levels, both compared with desmopressin (p

Background Renal transplant biopsies are essential in nephrology; however, they are invasive and complications can occur. Purpose To explore the risk of transplant kidney biopsy (TxB) complications in relation to possible preventive effects of desmopressin prophylaxis. Material and Methods A total of 515 consecutive TxB (375 patients, median age 53 years) were analyzed. In 252 TxB, the Resistive Index (RI) was measured right before the biopsy. A total of 282 patients had serum creatinine >150 µmol/L. In one of the six hospitals 39/282 patients consecutively received desmopressin (dose 0.3 µg/kg subcutaneously) as prophylaxis within 1 h before the biopsy. Fisher’s exact and χ2 test were used (odds ratio [OR], 95% confidence interval [CI]). Univariate and multiple binary logistic regression analyses were performed. A two-sided P value Results RI ≥ 0.8 was a risk factor for major TxB complications (OR 4.2, 95% CI 1.13–15.76). The risk for minor complications decreased with mean arterial blood pressure (MAP) (97.9 vs. 89.5 mmHg, OR 0.97, 95% CI 0.95–0.997). In a multiple regression analysis for overall biopsy complications, the risk remained increased for patients with RI ≥ 0.8 (OR 4.45, 95% CI 1.32–15.04). No patients (0/39) with desmopressin prophylaxis had a major complication versus 8/243 in the other group. In patients with serum creatinine >150 µmol/L, those with a higher MAP had more overall TxB complications (104.5 vs. 98.2 mmHg, OR 1.05, 95% CI 1.004–1.1). Conclusion RI ≥ 0.8 was a risk factor for major and overall complications and a lower MAP for minor biopsy complications. Desmopressin prophylaxis showed yet no verified benefit as prophylaxis in TxB.

Introduction: Percutaneous renal biopsy remains critical for the workup of renal allograft dysfunction but is associated with the risk of bleeding. Prophylactic intravenous desmopressin has been proposed to reduce bleeding risk in native renal biopsies, but its efficacy in the renal transplant population is unclear and adverse events such as severe hyponatraemia have been reported. Materials and Methods: We conducted a single-centre retrospective cohort study involving adult (≥21 years old) renal transplant recipients with impaired renal function (serum creatinine ≥150 μmol/L) who underwent ultrasound-guided renal allograft biopsies from 2011‒2015 to investigate the effect of prebiopsy desmopressin on the risk of bleeding and adverse events. Results: Desmopressin was administered to 98 of 195 cases who had lower renal function, lower haemoglobin and more diuretic use.Postbiopsy bleeding was not significantly different between the 2 groups (adjusted odds ratio [OR] 0.79, 95% confidence interval [CI] 0.26‒2.43, P = 0.68) but desmopressin increased the risk of postbiopsy hyponatraemia (sodium [Na]

COVID-19 has changed the nature of medical consultations, emphasizing virtual patient counseling, with relevance for patients with diabetes insipidus (DI) or hyponatraemia. The main complication of desmopressin treatment in DI is dilutional hyponatraemia. Since plasma sodium monitoring is not always possible in times of COVID-19, we recommend to delay the desmopressin dose once a week until aquaresis occurs allowing excess retained water to be excreted. Patients should measure their body weight daily. Patients with DI admitted to the hospital with COVID-19 have a high risk for mortality due to volume depletion. Specialists must supervise fluid replacement and dosing of desmopressin. Patients after pituitary surgery should drink to thirst and measure their body weight daily to early recognize the development of the postoperative syndrome of inappropriate antidiuresis (SIAD). They should know hyponatraemia symptoms. The prevalence of hyponatraemia in patients with pneumonia due to COVID-19 is not yet known, but seems to be low. In contrast, hypernatraemia may develop in COVID-19 patients in ICU, from different multifactorial reasons, for example, due to insensible water losses from pyrexia, increased respiration rate and use of diuretics. Hypernatraemic dehydration may contribute to the high risk of acute kidney injury in COVID-19. IV fluid replacement should be administered with caution in severe cases of COVID-19 because of the risk of pulmonary oedema.

Introduction Diagnosis, treatment monitoring and assessment of desmopressin effect in haemophilia A patients are performed by measurement of factor VIII activity (FVIII). The two assays commonly applied are the one‐stage assay and the chromogenic assay. Especially in non‐severe haemophilia A, discrepancies between these assays are common. It is still unestablished which assay corresponds best with bleeding phenotype and desmopressin effect. Aim To correlate FVIII levels measured by the one‐stage assay and by the chromogenic assay with bleeding phenotype and, additionally, to compare FVIII assay discrepancies before and after desmopressin administration. Method Factor VIII was measured in 130 non‐severe haemophilia A patients during routine visits to the outpatient clinic and/or during desmopressin testing. FVIII was measured by both the one‐stage assay and the chromogenic assay. Discrepancies between assays were defined as at least a twofold difference of FVIII or an absolute FVIII difference between measurements of ≥0.10 IU/mL. Bleeding phenotype was defined as annual number of treated bleedings (adjusted ABR). Results Hundred and thirty non‐severe haemophilia A patients were included. In 31/130 patients, assay results were discrepant. However, FVIII measurements with both assays correlated adequately with adjusted ABR. In addition, in 27/130 patients FVIII measurements at baseline and after desmopressin administration were analysed. In 13/27 patients, all measurements were either equivalent or discrepant when results were compared. In 14/27 patients, this was not the case as both equivalent measurements and discrepant measurements at different time points within one patient were observed. Conclusion Neither the one‐stage assay nor the chromogenic assay is superior in predicting bleeding phenotype. In addition, equivalent or discrepant FVIII results measured before desmopressin do not always predict FVIII assay results after desmopressin administration.

Modulating PD-1 expression can constrain tumor growth. Hodgkin's lymphoma patients commonly express PD-L1 on tumor cells. We report the case of a 60-year-old male patient with relapsed classical Hodgkin's lymphoma who suffered from immediate-onset chill, hyperthermia and polyuria following initial treatment with sintilimab, an anti-PD-1 monoclonal antibody. The results revealed central diabetes insipidus (cDI). After 3 months of treatment with glucocorticoids and desmopressin acetate, his symptoms and the results were consistent with the resolution of cDI and the treatment course was discontinued. Diabetes insipidus is a rare complication of immunotherapeutic treatment, and this is the first case report to our knowledge to have described immediate-onset cDI caused by anti-PD-1 treatment.Lay abstract For relapsed classical Hodgkin's lymphoma, anti-PD-1 monoclonal antibodies have been related to potent safety profiles and efficacy. Reported here is a case of a 60-year-old man diagnosed as having relapsed classical Hodgkin's lymphoma. He achieved a durable response over 4 months with four rounds of traditional chemotherapy, and then the disease relapsed. Sintilimab, an anti-PD-1 monoclonal antibody, was executed for salvage therapy. In spite of the patient-acquired durable response, central diabetes insipidus was detected after the first application of sintilimab. According to our knowledge this is the first case to report immediate-onset central diabetes insipidus caused by the treatment of anti-PD-1. In the present study, we discussed and analyzed the types and clinical causes of diabetes insipidus for this patient.

Purpose: To describe the otorhinolaryngological adverse effects of the main drugs used in urological practice. Materials and Methods: A review of the scientific literature was performed using a combination of specific descriptors (side effect, adverse effect, scopolamine, sildenafil, tadalafil, vardenafil, oxybutynin, tolterodine, spironolactone, furosemide, hydrochlorothiazide, doxazosin, alfuzosin, terazosin, prazosin, tamsulosin, desmopressin) contained in publications until April 2020. Manuscripts written in English, Portuguese, and Spanish were manually selected from the title and abstract. The main drugs used in Urology were divided into five groups to describe their possible adverse effects: alpha-blockers, anticholinergics, diuretics, hormones, and phosphodiesterase inhibitors. Results: The main drugs used in Urology may cause several otorhinolaryngological adverse effects. Dizziness was most common, but dry mouth, rhinitis, nasal congestion, epistaxis, hearing loss, tinnitus, and rhinorrhea were also reported and varies among drug classes. Conclusions: Most of the drugs used in urological practice have otorhinolaryngological adverse effects. Dizziness was most common, but dry mouth, rhinitis, nasal congestion, epistaxis, hearing loss, tinnitus, and rhinorrhea were also reported. Therefore, doctors must be aware of these adverse effects to improve adherence to the treatment and to minimize damage to the health of patients.

Background The way by which 1-deamino-8-D-arginine vasopressin (DDAVP) acts on platelets remains unclear. Data from the literature tend to show that there is no definite effect on platelet activation, but recent work has suggested that a subtype of platelets, activated by the combined action of collagen and thrombin, was triggered by DDAVP. Moreover, platelet microparticles (PMPs), which have been shown to be procoagulant, have rarely been studied in this context. The goal of this study was to analyze the effects of DDAVP on PMPs' release through platelet activation. Methods Fifteen out of 18 consecutive patients undergoing a therapeutic test with DDAVP were included. They were suffering from factor VIII deficiency or from von Willebrand disease. The expression of P-selectin and PAC-1 binding on platelets and the numbers of circulating PMPs were evaluated ex vivo before and after DDAVP infusion. Peripheral blood was collected on CTAD to limit artifactual platelet activation. Results DDAVP induced a significant decrease of platelet counts and volume. Only small changes of P-selectin expression and PAC-1 binding were observed. Considering PMPs, two populations of patients could be defined, respectively, with (120%, n = 6) or without (21%, n = 7) an increase of PMPs after DDAVP. The decrease in platelet counts and volume remained significant in the group of responders. Conclusion This study shows that DDAVP induces the generation/release of PMPs in some patients with factor VIII deficiency and von Willebrand disease 1 hour after DDAVP infusion.

INTRODUCTION There is an unmet need to characterize the diagnosis and management of patients with an unclassified bleeding disorder (UBD). METHODS Retrospective review of registered patients with UBD at our centre. Assessment including rotational thromboelastometry (ROTEM) and thrombin generation (TG) were used. RESULTS A total of 124 patients were identified; 91% female. Mean age of presentation was 38.3 years. Mean bleeding score was 8.8 (standard deviation [SD] 3.8); 6.6 in men (SD 1.4) and 9.7 in women (SD 3.3), which was significantly different (P

The bioequivalence of two formulations of desmopressin (dDAVP), a vasopressin analogue prescribed for nocturnal enuresis treatment in children, has been previously confirmed in adults but not in children. In this study, we aimed to study the pharmacokinetics (PK) and pharmacodynamics (PD) of these two formulations, in both fasted and fed children, including patients younger than 6 years of age. Previously published data from one PK study and one PK/PD study in children aged between 6 and 16 years were combined with a new PK/PD study in children aged between 6 months and 8 years, and analysed using population PK/PD modelling. Simulations were performed to further explore the relative bioavailability of both formulations and evaluate current dosing strategies. The complex absorption behaviour of the lyophilizate was modelled using a double input, linked to a one-compartmental model with linear elimination and an indirect response model linking dDAVP concentration to produced urine volume and osmolality. The final model described the observed data well and elucidated the complexity of bioequivalence and therapeutic equivalence of the two formulations. Simulations showed that current dosing regimens using a fixed dose of lyophilizate 120 μg is not adequate for children, assuming children to be in the fed state when taking dDAVP. A new age- and weight-based dosing regimen was suggested and was shown to lead to improved, better tailored effects. Bioequivalence and therapeutic equivalence data of two formulations of the same drug in adults cannot be readily extrapolated to children. This study shows the importance of well-designed paediatric clinical trials and how they can be analysed using mixed-effects modelling to make clinically relevant inferences. A follow-up clinical trial testing the proposed dDAVP dosing regimen should be performed. This trial has been registered at www.clinicaltrials.gov (identifier NCT02584231; EudraCT 2014-005200-13).

A 41-year-old man was diagnosed with hypogonadotropic hypogonadism managed with gonadotropins after routine fertility review. Eight months later he presented with new polydipsia and polyuria, lethargy and easy bruising. A full blood count showed 28% circulating blasts. A bone marrow biopsy confirmed a diagnosis of acute myeloid leukaemia with inv(3)(q21.3q26.2) with additional monosomy 7. Central diabetes insipidus (DI) was diagnosed following a water deprivation test. Pituitary magnetic resonance imaging showed a slightly thickened pituitary stalk, stable Rathke's cyst, and new absence of the pituitary bright spot. The patient was commenced on desmopressin and induction chemotherapy, subsequently requiring a bone marrow transplant. Bone marrow examination at 100 days post-transplant revealed cytogenetic remission. All symptoms of DI resolved and magnetic resonance imaging showed return of the posterior bright spot and a pituitary stalk of normal thickness. Biochemical hypogonadotropic hypogonadism persisted but was uninterpretable in the context of systemic illness and recent chemotherapy. DI is a rare complication of haematological malignancies, and the prevalence and pathophysiology of DI in this context are poorly understood. Pathogenic mechanisms proposed include leukaemic infiltration of the pituitary, interference with antidiuretic hormone synthesis, and abnormal thrombopoiesis influencing hormone levels. Particular cytogenetic abnormalities such as inv(3)(q21.3q26.2) and monosomy 7 appear to be more commonly associated with DI and also appear to confer worse outcomes. Aetiologies in the literature remain elusive but as DI is a recognised association of haematological malignancies it should be considered in a patient presenting with polydipsia and polyuria.

The transcription factor RAX is a paired-type homeoprotein that plays a critical role in eye and forebrain development of vertebrate species. RAX knockout mice have anophthalmia, cleft palate, abnormal hypothalamus, and display perinatal lethality. In humans, homozygous or compound heterozygous RAX mutations are reported to cause bilateral micro/anophthalmia without consistent associated features.Congenital Hypopituitarism can be associated with various eye or craniofacial anomalies but the co-occurrence of Congenital Hypopituitarism, anophthalmia, cleft palate and diabetes insipidus is very rare., SCOPUS: ar.j, info:eu-repo/semantics/published

Aims To systematically assess all available evidence on efficacy and safety of desmopressin for treating nocturia in patients with multiple sclerosis (MS). Methods This systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Studies were identified by electronic search of Cochrane register, Embase, Medline, Scopus (last search March 3, 2018) and by screening of reference lists and reviews. Results After screening of 7015 abstracts, 8 prospective, and 1 retrospective studies were included enrolling a total of 178 patients. The mean patient age ranged between 43 and 51 years. A significant decrease in the number of micturitions per night was reported in 5 studies. An increase in the maximum hours of uninterrupted sleep was only found in two studies. A significant reduction of the volume of nocturnal incontinence was described in one study. The patient satisfaction rates ranged from 56% to 82%. The rate of adverse events was between 0% and 57.9%. The rate of hyponatremia ranged from 0% to 23.5% and other commonly reported adverse events were headache, nausea, fluid retention, rhinitis/epistaxis, malaise, and swollen ankles. Risk of bias and confounding was relevant in all studies. Conclusions Preliminary data suggest that desmopressin might be effective for treating nocturia in patients with MS. However, adverse events are relatively common, the overall quality of evidence is low and the number of studied patients is very limited. Further studies with newer formulations of desmopressin are highly warranted.

Aims To evaluate the impact of compliance on the therapeutic effects of Desmopressin, as well as the importance of establishing the voiding school for low-compliance children in primary monosymptomatic enuresis treatment. Methods Eighty-nine patients with primary monosymptomatic enuresis treated with Desmopressin were observed during the 2017–2020 at University Children’s Hospital Belgrade, Serbia. The average patients age was 7.7 ± 2.4 years; 65 (73%) were boys and 24 (27%) % were girls. After the 3 months of Desmopressin treatment, the effect of therapy was evaluated according to the compliance. After the treatment, low-compliance patients and their parents were suggested to visit a voiding school. Results A significant decrease in the median enuresis frequency was noticed during the Desmopressin treatment (25.0 (20.0–26.0) vs 10.0 (2.0–17.0) per month, before vs after treatment, respectively) (p p p p Conclusion Compliance considerably influences the beneficial effects of Desmopressin. Patients with poor therapeutic effects should be evaluated for compliance and introduced to voiding school.

PURPOSE: The goal of this study was to determine if the US adult population with nocturia (waking from sleep at night to void) can easily take medications (desmopressin acetate) approved by the US Food and Drug Administration for nocturia. The study examined: (1) the prevalence of comorbid conditions, laboratory abnormalities, and concomitant medications that increase risk of desmopressin use; and (2) whether these factors are associated with age or nocturia frequency. METHODS: Using a cross-sectional analysis of four US National Health and Nutrition Examination Survey (NHANES) waves (2005–2012), a total of 4111 participants aged ≥50 years who reported ≥2 nightly episodes of nocturia were identified. The main outcome was frequency of contraindications and drug interactions as described in US Food and Drug Administration–approved prescribing information. These prescribing concerns were matched to examination findings, medical conditions, concomitant medications, and laboratory results of NHANES participants. The associations between prescribing concerns and nocturia severity and age groups were examined. FINDINGS: The mean participant age was 65.7 years (95% CI, 65.3–66.1), and 45.5% were male. Desmopressin prescribing concerns were present in 80.5% (95% CI, 78.0–82.9) of those ≥50 years of age with nocturia; 50.0% (95% CI, 47.0–53.0) had contraindications, and 41.6% (95% CI, 39.3–44.0) took a concomitant drug that could increase risk of low serum sodium. Desmopressin contraindications were higher with older age (P < 0.001) and present in 73.2% (95% CI, 69.3–77.1) of those ≥80 years of age. IMPLICATIONS: Using NHANES data, this study showed that older US adults with nocturia have a high prevalence of medical conditions, concomitant medications, and baseline laboratory abnormalities that likely increase the risk of potentially severe adverse side effects from desmopressin use. A medication designed and approved for a clinical symptom that is most common in older adults could not be taken by most of the older adults with the symptom.

Rathke's cleft cyst (RCC) is a common incidental tumor in the hypothalamic-pituitary region. Some reports have shown that the clinical symptoms and endocrine functions of symptomatic RCCs are temporarily improved by glucocorticoid administration. However, it is still unknown whether glucocorticoid treatment is effective for symptomatic RCCs according to long-term observations. In this study, we describe the long-term clinical outcomes of two cases of glucocorticoid-treated biopsy-proven secondary hypophysitis caused by RCCs. We summarize the symptoms, imaging findings, and endocrine evaluations of two symptomatic RCC patients with concomitant hypophysitis before and after prednisolone treatment. In both evaluated cases, visual impairments and altered endocrine parameters were present due to chiasm and stalk compression; these outcomes improved after shrinkage of RCCs in response to prednisolone administration, and partial recovery of anterior pituitary hormone secretion was observed. However, in both cases, the deficits in anterior pituitary hormone secretion recurred, possibly due to persistent inflammatory infiltration in the RCCs and pituitary glands. After relapse of hypophysitis, anterior hormone secretion did not fully recover. In our cases of secondary hypophysitis caused by RCCs, prednisolone administration had an early effect of cyst shrinkage, followed by partial improvements in clinical symptoms and pituitary functions. However, long-term observation showed that prednisolone treatment did not contribute to complete improvement in anterior pituitary hormone dysfunction.

BACKGROUND Monosymptomatic enuresis nocturna patients are shown to have disrupted blood-pressure regulation accompanying polyuria. In our study, we aimed to research the desmopressin response of enuresis patients with blood-pressure regulation problems. METHODS The study included 175 patients, aged from 6-15 years, with a diagnosis of monosymptomatic enuresis nocturna. Before treatment, 24 h ambulatory blood-pressure monitoring (ABPM) was used to identify 52 non-dipper patients and 73 patients with normal results. The responses to desmopressin treatment and clinical and demographic characteristics affecting response were compared. RESULTS The response to desmopressin treatment was found to be significantly low in the patients who were non-dippers on 24 h ABPM before treatment compared to those with normal ABPM results (P < 0.05). Similarly, the waking problems in the non-dipper group were found to be high by a significant degree (P < 0.05). In the non-dipper group, the systolic non-dipping rate was higher. CONCLUSIONS Before desmopressin use, assessment of patients with a 24 h ABPM may be beneficial to select the method to be used for treatment.

Transsphenoidal surgery (TSS) is the treatment of choice in Cushing’s disease. However, recurrence rates are substantial and currently there are no robust predictors of late prognosis. As accumulating evidence challenge the accuracy of the traditionally used early postoperative cortisol values, alternative tests are required. The study of Cambos et al., published in a recent issue of the European Journal of Endocrinology, adds to the existing data that support a role of the desmopressin test as an early and reliable predictive marker in successfully TSS-treated patients. However, despite these promising data, the use of this test is hampered by the fact that it can be applied only in patients with a documented preoperative positive test. Moreover, the lack of robust criteria to define positive postoperative responses represents another major limitation.

The deficiency or abnormal activity of von Willebrand factor, a multi-adhesive protein which binds platelets to exposed subendothelium and carries factor VIII in circulation, is responsible for von Willebrand disease, the most frequent inherited bleeding disorder. Clinical symptoms are characterized by mucous membrane and soft tissue bleeding, bleeding after surgery and rarely joint and gastrointestinal bleeding. Intriguingly, also factor VIII, the protein deficient in hemophilia A, may be variably reduced because VWF stabilizes it into circulation. Treatment strategies are well designed for patients with levels of VWF activity

Metastatic disease represents a serious and often fatal development in patients with solid tumours, including women with breast cancer and dogs with mammary tumours. Therefore, preventing and treating metastatic disease has remained a priority in cancer research. Desmopressin, a synthetic derivative of vasopressin, traditionally used to treat patients with bleeding disorders, has been proposed as a potential anti-metastatic agent due to its effect on haemostasis as well as multiple other anti-proliferative and anti-angiogenic mechanisms. The purpose of this study was to retest desmopressin in dogs with mammary carcinomas. A prospective randomized study was performed. Twenty-four dogs with mammary carcinomas were enrolled; 12 dogs received perioperative desmopressin and 12 received placebo. All dogs underwent standard pre-surgical staging followed by complete resection of all tumours. Intact dogs were spayed. All tumours were graded and classified according to the published guidelines. Follow-up was performed every 4 months the first year and every 6 months thereafter. Necropsies were requested on all dogs. There was no difference in time to primary metastasis or survival between desmopressin treated dogs and the placebo arm (P = .43 and .73, respectively). The distribution of negative prognostic factors, including tumour grade, stage, and high vs low bioscore (refined flexible bioscoring) category between arms was not statistically different, even though more dogs in the placebo arm had grade 3 tumours and high bioscores. Based on the results of this study, perioperative desmopressin does not prevent metastasis in dogs with mammary carcinomas.

Objective To explore the influence of desmopressin on gonadotropin-induced spermatogenesis in patients with pituitary stalk interruption syndrome (PSIS). Methods A single-center retrospective cohort study was conducted. All patients with PSIS had both gonadotropin and growth hormone (GH) deficiency. Patients were divided into desmopressin and nondesmopressin groups. The desmopressin and nondesmopressin groups were defined by the presence or absence of central diabetes insipidus, which determined whether the patient received desmopressin or not. Results The average age of gonadotropin therapy was 24.3 and 26.1 in the desmopressin and nondesmopressin groups, respectively. The rate of successful spermatogenesis in the 2 groups was 31.58% and 77.27%, respectively. The period for first sperm appearance was 13.62 ± 5.95 and 13.48 ± 6.69 months, respectively. A multivariable Cox proportional hazards model found that the adjusted hazard ratio for desmopressin was 0.260, indicating a “possible” detrimental effect of desmopressin on spermatogenesis. Central diabetes insipidus would be expected to show a similar detrimental effect. The spermatogenesis rate decreased with increased dosage of desmopressin. In the nondesmopressin group, the rate of spermatogenesis was similar between the GH group and the non-GH subgroup. The GH group had higher sperm count and concentration than the non-GH group. Conclusion A minority of patients with PSIS had mild diabetes insipidus and received desmopressin therapy. The spermatogenesis rate decreased with increasing desmopressin dosage. In addition, GH supplementation did not affect the spermatogenesis rate.

Background Kidney biopsy is the gold standard for diagnosing kidney disease but may result in bleeding, especially in uraemia. DDAVP (1-deamino-8-d-arginine vasopressin) may reduce uraemic bleeding but guidelines on its use are lacking. Aim To evaluate whether DDAVP reduced bleeding complications after percutaneous kidney biopsies. Methods We searched CENTRAL, PubMed, Embase, LILACS, WHO Trials Registry and ClinicalTrials.gov until May 2019 for randomised controlled trials (RCT), quasi-RCT and prospective cohort studies that compared DDAVP with placebo or no intervention, prior to native or allograft kidney biopsy. The primary outcome was post-biopsy bleeding. Secondary outcome was adverse events related to DDAVP. Results Abstracts of 270 identified papers were examined and 24 selected for evaluation. Two studies, one RCT and one prospective cohort that collectively evaluated 738 native kidney biopsies, met the inclusion criteria. One enrolled individuals with serum creatinine ≤1.5 mg/dL (132 μmol/L) and/or estimated glomerular filtration rate ≥60 mL/min/1.73 m2 while the other evaluated biopsies with serum creatinine >150 μmol/L. DDAVP was administered as a single subcutaneous dose of 0.3 μg/kg in both studies. Data were not pooled for meta-analysis due to clinical heterogeneity. GRADE quality of evidence from these two studies was low for DDAVP preventing any bleeding complication after native kidney biopsy. Low quality evidence suggested that adverse effects were not increased in DDAVP therapy. No prospective studies evaluated DDAVP in transplant kidney biopsies. Conclusion Currently available prospective data are insufficient to support the routine use of DDAVP prior to percutaneous kidney biopsies hence high quality trials are required.

Gastrointestinal (GI) bleeding is distinctive of severe von Willebrand disease (VWD), generally arising in older patients; in most cases, blood transfusion and hospitalization are required. The presence of arteriovenous malformations is often described when endoscopic examinations are performed. Patients with congenital type 3, 2A, and 2B are those most frequently affected by this symptom, possibly due to the loss of high-molecular-weight multimers of von Willebrand factor (VWF). GI bleeding can also occur in patients affected by acquired von Willebrand syndrome. Endoscopic examination of the GI tract is necessary to exclude ulcers and polyps or cancer as possible causes of GI bleeding. In congenital VWD, prophylaxis with VWF/factor VIII concentrates is generally started after GI-bleeding events, but this therapy is not always successful. Iron supplementation must be prescribed to avoid chronic iron deficiency. Possible rescue therapies (high-dose statins, octreotide, thalidomide, lenalidomide, and tamoxifen) were described in a few case reports and series; however, surgery may be necessary in emergency situations or if medical treatment fails to stop bleeding. In this article, we present several clinical cases that highlight the clinical challenges of these patients and possible strategies for their long-term management.

The cause of hemophilia A carrier bleeding is not well established. Desmopressin (DDAVP), used clinically to treat or prevent bleeding, can also be used as a medical stress surrogate. This study’s objective was to compare the response to DDAVP in hemophilia A carriers with that in normal control patients. Bleeding was assessed by the International Society on Thrombosis and Hemostasis Bleeding Assessment Tool (ISTH-BAT). DDAVP (0.3 μg/kg) was administered either IV or subcutaneously (SC), and blood was drawn at baseline and 1, 2, and 4 hours postadministration. Blood was assessed for factor VIII (FVIII) level, von Willebrand factor (VWF) antigen (VWF:Ag), VWF activity (VWF:RCo or VWF:GPIbM), thromboelastography (TEG), and thrombin generation assay (TGA) at all points, and for VWF propeptide (VWFpp):Ag ratio and ABO blood type at baseline. Carriers were older than control patients (median age, 34 and 21 years, respectively; P = .003) and had higher ISTH-BAT bleeding scores (median bleeding score, 8 and 0, respectively; P = .001). Carriers had a significantly reduced FVIII response to DDAVP compared with control patients (P ≤ .0001). When only carriers with normal baseline FVIII levels (n = 10) were included, carriers maintained a reduced FVIII response (P ≤ .0001). Furthermore, participants with abnormal bleeding scores had a significantly lower FVIII response to DDAVP compared with those with normal bleeding scores (P = .036). Hemophilia A carriers have a lower and less sustained FVIII response to DDAVP, suggesting an impaired ability to respond to hemostatic stress, which contributes to bleeding.

INTRODUCTION Desmopressin is an effective haemostatic agent for patients with non-severe haemophilia A; however, response may differ between patients of similar severity. Responsiveness is classified based on various cut-off values for plasma levels of FVIII post-desmopressin administration. Patients may be classified differently depending on the values chosen. AIM To classify desmopressin response in non-severe haemophilia A patients with respect to current test-response definitions. Also, to characterize relationships between test response and clinical outcome of desmopressin use. METHODS Current desmopressin test-response definitions were obtained from the literature. We adopted peak FVIII level (at 1 hour post-administration) ≥50 IU/dL and

Objective To establish the treatment efficacy of practitioner-assisted bell-and-pad alarm therapy in children with enuresis between the ages of 5 and 16 years by retrospective medical chart review of 2861 children in multiple clinical settings. Study design This review was conducted across 7 Australian clinical practices. The primary outcome measure was the time taken for children with either primary, secondary, monosymptomatic, or nonmonosymptomatic enuresis to be dry for 14 consecutive nights. The secondary outcome measure was to determine relapse rates, defined as 1 symptom recurrence per month post interruption of treatment. Data were analyzed by correlation and χ2 test via IBM SPSS Statistics (version 22). Results The overall success rate of the bell and pad treatment was 76%, irrespective of age. The mean treatment time to achieve dryness was 62.1 ± 30.8 days, and the relapse rate was 23%. Concurrent bowel dysfunction was associated with a slightly lower success rate (74%). Concurrent lower urinary tract symptoms were associated with a lower success rate (73%) and greater relapse (1.75 times more likely to relapse). Children with secondary enuresis had significantly greater success than those with primary enuresis (82% vs 74%). Conclusion The type of alarm therapy reported in this study is highly effective. This study will provide the basis for clinical guidelines and practice tools for clinicians, which will help to reduce variation in care pathways for alarm treatment for enuresis.

Glioblastoma is a devastating malignancy with a dismal survival rate. Currently, there are limited prognostic markers of glioblastoma including IDH1, ATRX, MGMT, PTEN, EGFRvIII, and others. Although these biomarkers for tumor prognosis are available, a surgical biopsy must be performed for these analyses, which has morbidity involved. A non-invasive and readily available biomarker is sought after which provides clinicians prognostic information. Sodium is an electrolyte that is easily and quickly obtained through analysis of a patient's serum. Hyponatremia has been shown to have a predictive and negative prognostic indication in multiple cancer types, but the role of glioblastoma patients' serum sodium at the time of diagnosis in predicting glioblastoma patient survival has not been determined. We assessed whether hyponatremia at the time of glioblastoma diagnosis correlates to patient survival and show that in our cohort of 200 glioblastoma patients, sodium, at any level, did not significantly correlate to glioblastoma survival, unlike what is seen in multiple other cancer types. We further demonstrate that inducing hyponatremia in an orthotopic murine model of glioblastoma has no effects on tumor progression and survival.

Desmopressin increases endogenous factor VIII levels in hemophilia A. Large inter-individual variation in the response to desmopressin is observed. Patients with a lower baseline factor VIII activity tend to show a reduced response, therefore, desmopressin is less frequently used in moderate hemophilia A patients (baseline factor VIII activity 1-5 international units/deciliter), even though factor VIII levels may rise substantially in some of them. We aim to describe the response to desmopressin in moderate hemophilia A patients and to identify predictors. We selected data on 169 patients with moderate hemophilia from the multicenter Response to DDAVP In non-severe hemophilia A patients: in Search for dEterminants (RISE) cohort study. Adequate response to desmopressin was defined as a peak factor VIII level ≥ 30, and excellent response as ≥ 50 international units/deciliter after desmopressin administration. We used univariate and multiple linear regression techniques to analyze predictors of the peak factor VIII level. Response was considered adequate in 68 patients (40%), of whom 25 showed excellent response (15%). Intravenous administration, age, pre-desmopressin factor VIII activity and von Willebrand factor antigen, peak von Willebrand factor activity and desmopressin-induced rise in von Willebrand factor antigen were significant predictors of peak factor VIII level and explained 65% of the inter-individual variation. In 40% of moderate hemophilia A patients, desmopressin response was adequate, thus it is important not to with-hold this group of patients from desmopressin responsiveness. Among the six predictors that we identified for desmopressin-induced factor VIII rise, factor VIII activity and desmopressin-induced rise in von Willebrand factor antigen had the strongest effect.

Background Nonsevere haemophilia A (HA) patients can be treated with desmopressin. Response of factor VIII activity (FVIII:C) differs between patients and is difficult to predict. Objectives Our aims were to describe FVIII:C response after desmopressin and its reproducibility by population pharmacokinetic (PK) modelling. Patients and Methods Retrospective data of 128 nonsevere HA patients (age 7–75 years) receiving an intravenous or intranasal dose of desmopressin were used. PK modelling of FVIII:C was performed by nonlinear mixed effect modelling. Reproducibility of FVIII:C response was defined as less than 25% difference in peak FVIII:C between administrations. Results A total of 623 FVIII:C measurements from 142 desmopressin administrations were available; 14 patients had received two administrations at different occasions. The FVIII:C time profile was best described by a two-compartment model with first-order absorption and elimination. Interindividual variability of the estimated baseline FVIII:C, central volume of distribution and clearance were 37, 43 and 50%, respectively. The most recently measured FVIII:C (FVIII-recent) was significantly associated with FVIII:C response to desmopressin (p Conclusion FVIII:C response to desmopressin in nonsevere HA patients was adequately described by a population PK model. Large variability in FVIII:C response was observed, which could only partially be explained by FVIII-recent. FVIII:C response was not reproducible in a small subset of patients. Therefore, monitoring FVIII:C around surgeries or bleeding might be considered. Research is needed to study this further.

Background People with schizophrenia and medical comorbidities are often on multiple medications to manage their symptoms. Herein we present a case of drug-drug interaction (meloxicam and desmopressin), in a patient also on clozapine, that ultimately resulted in hyponatremia and seizure. Methods The patient provided consent to have his case published. We searched PubMed and after reviewing 321 articles, 11 were chosen for relevance. Results Meloxicam enhanced the adverse effect (hyponatremia) of desmopressin and was the likely culprit. Conclusions In a patient with higher ADH levels, as in our patient taking desmopressin, the addition of an NSAID could further increase water retention and worsen hyponatremia; indeed, meloxicam was the only new medication added to the patient's regimen, and a drug interaction calculator supports the desmopressin-meloxicam drug-drug interaction as the culprit. We urge clinicians to avoid the use of desmopressin in patients with schizophrenia as this can lead to water intoxication. As meloxicam may worsen desmopressin-induced hyponatremia and could result in seizure, one should avoid using NSAIDs in patients with schizophrenia whom are also prescribed vasopressin/desmopressin. Serum sodium levels should be closely monitored in patients with schizophrenia whose regimen includes desmopressin.