Nocturnal Urine Research Articles

The impact of nocturnal polyuria in older people with nocturnal LUTS.

Bladder dysfunctions often express the presence of lower urinary tract symptoms (LUTS) and are common in older people. The aim of this study was to analyze the micturition, incontinence and residual in older subjects, evaluating the role of nocturnal polyuria. Eighty-six patients aged 65 or older with invalidating LUTS were hospitalized for 24 hours. The maximum bladder capacity, mean micturition volume, post voiding residual and incontinence volume were recorded and analyzed day-time and night-time. Three groups were defined, i.e. nocturia, nocturnal incontinence and nocturnal polyuria (NP), and patients with or without NP were analyzed. With a majority of female patients 85% and a mean age of 74.3±5.96 years, a high incidence of nocturia (76%) was observed. NP was associated with nocturia in 56 patients (86%). In the three groups, the maximum bladder capacity and mean micturition volume were statistically higher during the night. Patients with nocturia or nocturnal incontinence associated to NP presented with a higher nocturnal maximum bladder capacity and mean micturition volume. A higher nocturnal post-void residual (PVR) was observed in patients with Nocturnal Incontinence associated with NP (P=0.03). Patients without NP presented significantly higher diurnal results. Nocturnal LUTS in older people is the result of a high nocturnal urine production related to NP with a higher nocturnal bladder capacity. The analyses of micturition, incontinence and PVR, and the accurate evaluation of the presence or absence of NP seems to be the key point for a better therapeutic choice in patients suffering by Nocturnal LUTS.

Association of Increased Nocturnal Urine Volume with a Gonadotropin- Independent Reduction of Nighttime Serum Testosterone Level in Male Nocturia Patients

Nocturia is common in the aging male. One factor is an increased nocturnal urine volume. However, the reasons for the increased urine amount in the night remain unclear. Sex steroid hormone has been found to play a role in the regulation of water/solute excretion. It would be valuable to know whether there is any correlation between androgen status and nocturnal urine production in men with nocturia. The study included 22 male patients (mean age 75.6 ± 6.2) with nocturia (＞2 micturition per night). All of them maintained a voiding diary and collected urine for 3 successive days. Samples of urine collected separately at daytime and nighttime were sent for assay of sodium and calcium. Serum samples at 7 am and midnight were collected for determination of testosterone, luteinizing hormone (LH), atrial natriuretic peptide (ANP) and aldosterone with radioimmunoassay. We correlated the ratio of nocturnal urine volume over 24 h urine volume (N/W) with various parameters using Pearson's correlation test. Patients void 4.6 ± 2.1 (range 2.0-9.5) times per night. The ratio of nocturnal urine volume ranges from 0.22 to 0.69, with a mean of 0.43. There is a significant positive correlation between nighttime sodium excretion and the ratio of nocturnal urine volume, while excretion of calcium, either in daytime or in nighttime, does not have significant correlation. Interestingly, patients with higher ratio of nocturnal urine volume have lower serum testosterone level in the midnight, while it does not have significant correlation in the morning. Serum LH level, either at 7 am or at midnight, shows no significant correlation with the ratio of nocturnal urine volume. Increased ANP and aldosterone were seen associated with increased N/W. This study shows that the increased nocturnal urine excretion is mainly due to an increased nighttime sodium excretion and is associated with a gonadotropin-independent reduction of serum testosterone level. Future studies are required to determine the significance of and causes for the decreased nighttime serum androgen level in male patients with nocturnal polyuria.

Efficacy and Safety of Desmopressin Add-On Therapy for Men with Persistent Nocturia on α-Blocker Monotherapy for Lower Urinary Tract Symptoms: A Randomized, Double-Blind, Placebo Controlled Study

We investigated the efficacy and safety of desmopressin add-on therapy for men with persistent nocturia on α-blocker for lower urinary tract symptoms in this placebo controlled study. The study included men 40 to 65 years old with lower urinary tract symptoms and persistent nocturia despite α-blocker therapy for at least 8 weeks. Patients were randomized to once daily placebo or desmopressin 0.2 mg for 8 weeks. The primary end point was to assess changes in the mean number of nocturia episodes from baseline to the final assessment. Other secondary end points and adverse events were evaluated. A total of 86 patients were randomized to treatment, including placebo in 39 and desmopressin 0.2 mg in 47. Baseline characteristics were similar in the 2 groups. The desmopressin add-on group was significantly superior to placebo in terms of the change from baseline in the mean number of nocturia episodes (-1.13 ± 0.92 vs -0.68 ± 0.79, p = 0.034), the changes in nocturnal urine volume (p <0.001), total I-PSS (International Prostate Symptom Score) (p = 0.041), the nocturnal polyuria index (p = 0.001) and ICIQ-N (International Consultation on Incontinence Questionnaire-Nocturia) (p = 0.001), and the willingness to continue (p = 0.025). The incidence of adverse events in the desmopressin add-on group was similar to that in the placebo group. Most adverse events were mild. Desmopressin add-on therapy in men 40 to 65 years old with persistent nocturia on α-blocker monotherapy for lower urinary tract symptoms is effective and well tolerated.

Effect of naftopidil on brain noradrenaline-induced decrease in arginine-vasopressin secretion in rats

Naftopidil, an α1-adrenoceptor antagonist, has been shown to inhibit nocturnal polyuria in patients with lower urinary tract symptom. However, it remains unclear how naftopidil decreases nocturnal urine production. Here, we investigated the effects of naftopidil on arginine-vasopressin (AVP) plasma level and urine production and osmolality in rats centrally administered with noradrenaline (NA). NA (3 or 30 μg/kg) was administered into the left ventricle (i.c.v.) of male Wistar rats 3 h after naftopidil pretreatment (10 or 30 mg/kg, i.p.). Blood samples were collected from the inferior vena cava 1 h after NA administration or 4 h after peritoneal administration of naftopidil; plasma levels of AVP were assessed by ELISA. Voiding behaviors of naftopidil (30 mg/kg, i.p.)-administered male Wistar rats were observed during separate light- and dark cycles. Administration of NA decreased plasma AVP levels and elevated urine volume, which were suppressed by systemic pretreatment with naftopidil (30 mg/kg, i.p.). Urine osmolality decreased 1 h after NA administration. However, naftopidil by itself had no effect on plasma AVP levels or urodynamic parameters during light- and dark cycles. Our findings suggest that systemic administration of naftopidil could prevent central noradrenergic nervous system-mediated decline in AVP secretion and increase in urine production in rats.

Prognostic Features for Objectively Defined Urinary Continence after Radical Cystectomy and Ileal Orthotopic Neobladder in a Contemporary Cohort

We objectively quantified daytime and nocturnal continence rates, anddefined predictive features for favorable continence outcomes after radical cystectomy and orthotopic ileal neobladder creation. At 1 institution 1,012 cystectomies were performed between 2004 and 2015. Questionnaires evaluating the continence status were sent to 244 patients. To objectify postoperative urine loss daytime and nocturnal pad tests were performed. Continence was defined as the need for up to 1 safety pad and urine loss 10 gm or less per test. Predefined associative features were tested for an influence on continence outcomes. Statistical analysis was done with the Fisher exact and Mann-Whitney U tests, and linear logistic regression models. Significance was considered at p <0.05. A total of 188 patients (77.0%) returned the questionnaires. Median followup was 61 months. Median daytime pad use was 1 pad per day (range 0 to 9). Median daily urine loss based on standardized pad testing was 8 gm (range 0 to 2,400). During the night a median of 1 pad (range 0 to 7) was used and median nocturnal urine loss was 28.5 gm (range 0 to 1,220). The continence rate was 54.3% during the day and 36.3% at night. On multivariate analysis good preoperative ECOG (Eastern Cooperative Oncology Group) status (OR 2.987, p=0.010), retained sensation of bladder filling (OR 6.462, p = 0.003) and preoperative coronary heart disease (OR 0.036, p = 0.002) were independent predictors of daytime success. Based on preoperative risk factors a simple predictive score for daytime continence was created (AUC 0.725, p <0.001). Continence rates after orthotopic ileal neobladder creation are lower than previously described when objective continence definitions are applied. Patients with good performance status, without coronary heart disease and with retained sensation of orthotopic ileal neobladder filling have better daytime continence outcomes.

Circadian Rhythms in Water and Solute Handling in Adults with a Spinal Cord Injury

We evaluated nocturnal urine production and circadian rhythms of renal function (glomerular filtration, and water and solute diuresis) in adults with spinal cord injury compared to controls. This prospective observational study was done at Ghent University Hospital, Belgium. Participants were asked to perform a 24-hour urine collection. A blood sample was taken to calculate the diuresis rate and the renal clearance of creatinine, free water, solutes, sodium and urea. A total of 119 patients were divided into 32 with spinal cord injury, and 68 controls with and 19 without nocturnal polyuria. Spinal cord injured patients showed no circadian rhythms in the diuresis rate or in the renal clearance of creatinine, free water, solutes, sodium or urea. Controls without nocturnal polyuria reported a lower nighttime diuresis rate and lower nighttime clearance of creatinine, solutes, sodium and urea compared to daytime levels. Controls with nocturnal polyuria had no circadian rhythms in the diuresis rate or creatinine clearance and a significant increase in nocturnal free water clearance compared to daytime levels. Comparing the mechanisms underlying nocturnal urine production between patients with spinal cord injury and controls revealed important differences. Spinal cord injured patients showed absent circadian rhythms in the renal clearance of creatinine (glomerular filtration), free water (water diuresis) and solutes such as sodium and urea (solute diuresis). Future research must be done to evaluate the role of patient stratification to find the most effective and safe treatment or combination of treatments for spinal cord injured patients with complaints or complications related to nocturnal polyuria.

Urinary incontinence after high-dose-rate brachytherapy boost treatment for prostate cancer

PurposeTo evaluate urinary incontinence (UI) and to elucidate potential risk factors important for the appearance or deterioration of pre-existing UI after high-dose-rate boost treatment of prostate cancer. Methods and MaterialsThe change in grade of UI regarding the state at the start of treatment was assessed in 88 patients, consecutively treated from October 2006 through April 2011 with high-dose-rate brachytherapy of 3 × 6–7 Gy to 50–50.4 Gy of external-beam radiation. Increase in UI grade was defined as deterioration of UI (DUI). The impact of patients and treatment characteristics on third year prevalence of DUI was analyzed by using binary logistic regression method. ResultsAt third year, DUI of followup was evidenced in 17/81 (20.9%) patients. It significantly impacted micturition quality (p = 0.015) and was associated with D2ccbladdervolume (odds ratio [OR]: 1.14; 95% confidence interval [CI]: 1.03–1.26; p = 0.010), diabetes (OR: 6.73; 95% CI: 1.17–38.56; p = 0.032), and initial nocturnal micturition frequency (OR: 3.72; 95% CI: 1.03–13.04; p = 0.045). Based on a multivariate model, a range of “safe” D2ccbladdervolume(EQD2) doses is suggested (no risk factor: 21.9 Gy, frequent initial nocturnal micturition only: 12.0 Gy, diabetes only: 7.6 Gy, both risk factors: no safe dose). ConclusionsThe study featured on urinary bladder base as a risk structure for UI. By taking account of the dose to urinary bladder base in conjunction with diabetes and initial nocturnal micturition frequency, the risk of UI could be reduced.

Assessment of Blood Pressure in Primary Monosymptomatic Nocturnal Enuresis

Introduction: Enuresis is defined as the repeated voiding of urine into bed at least twice a week for at least 3 consecutive months in a child who is at least 5 years of age. Primary enuresis occurs in children who have never been consistently dry through the night. Monosymptomatic enuresis has no associated daytime symptoms. Increased nocturnal urine production in primary nocturnal enuretic patients could possibly be associated with autonomic nervous system dysfunction. The aim of this study was to investigate autonomic nervous system function in enuretic children. Materials and Methods : In this study, children with monosymptomatic primary nocturnal enuresis (MPNE) and healthy children without MPNE were enrolled and their blood pressure was measured twice a day (in the morning and afternoon). Urinalysis, urine electrolyte levels, urinary culture, and urinary system ultrasound were performed in all the children. They were also requested to have a diary about daily fluid intake and the volume of daily urine. Results: The MPNE group comprised 100 children (M/F: 58/42) and the control group included 100 healthy children (M/F: 51/49). The mean age of the children was 8.1±2.3 and (8.9±2.53 years in MPNE and control groups, respectively. The mean diastolic blood pressure (DBP) during the nighttime and daytime did not differ between the groups (p-value>0.05); however, the mean systolic blood pressure (SBP) was significantly higher in the nighttime in the MPNE group (p-value 0.05). Conclusions: Nighttime SBP was significantly higher in children with MPNE. These subtle abnormalities of the circadian blood pressure regulation may reflect autonomic nervous system dysfunction and contribute to the pathogenesis of MPNE. Keywords : Child; Enuresis; Blood pressure; Autonomic dysfunction

Assessment of Blood Pressure in Primary Monosymptomatic Nocturnal Enuresis

Introduction: Enuresis is defined as the repeated voiding of urine into bed at least twice a week for at least 3 consecutive months in a child who is at least 5 years of age. Primary enuresis occurs in children who have never been consistently dry through the night. Monosymptomatic enuresis has no associated daytime symptoms. Increased nocturnal urine production in primary nocturnal enuretic patients could possibly be associated with autonomic nervous system dysfunction. The aim of this study was to investigate autonomic nervous system function in enuretic children.Materials and Methods: In this study, children with monosymptomatic primary nocturnal enuresis (MPNE) and healthy children without MPNE were enrolled and their blood pressure was measured twice a day (in the morning and afternoon). Urinalysis, urine electrolyte levels, urinary culture, and urinary system ultrasound were performed in all the children. They were also requested to have a diary about daily fluid intake and the volume of daily urine.Results: The MPNE group comprised 100 children (M/F: 58/42) and the control group included 100 healthy children (M/F: 51/49). The mean age of the children was 8.1±2.3 and (8.9±2.53 years in MPNE and control groups, respectively. The mean diastolic blood pressure (DBP) during the nighttime and daytime did not differ between the groups (p-value&gt;0.05); however, the mean systolic blood pressure (SBP) was significantly higher in the nighttime in the MPNE group (p-value&lt;0.05) but did not differ between the groups during the daytime (p-value&gt;0.05).Conclusions: Nighttime SBP was significantly higher in children with MPNE. These subtle abnormalities of the circadian blood pressure regulation may reflect autonomic nervous system dysfunction and contribute to the pathogenesis of MPNE.Keywords: Child; Enuresis; Blood pressure; Autonomic dysfunction

Efficacy of Desmopressin to Treat Nocturnal Polyuria in Elderly Men: Effects on Sleep Quality

Background: We investigated the efficacy of desmopressin in elderly patients with nocturnal polyuria (NP) to evaluate its effects on sleep quality. Methods: Patients with NP (defined as the nighttime urine production >33% of total 24-hour urine volume determined from a frequency-volume chart) were recruited. Desmopressin (0.2 mg) was treated orally at bedtime for 12 weeks. The participants completed the Medical Outcomes Study (MOS) Sleep Scale. Results: The mean patient age was 62.7 ± 13.0 (range 42-78 years). The mean symptom duration was 42.2 ± 39.7 months. The number of nocturia episodes (from 3.49 ± 1.83 to 2.03 ± 1.35, p = 0.01), nocturnal urine volume (p = 0.01), NP index (p = 0.01), and nocturia index (p = 0.01) decreased significantly after treatment with desmopressin. Among the MOS Sleep Scale categories, hours slept/night (p = 0.042), shortness of breath (p = 0.019), and adequacy of sleep (p = 0.001) changed significantly with a decrease in the number of nocturia episodes. Adverse events were mild. Conclusions: Desmopressin is an effective treatment for NP and improved sleep quality in elderly men.

Reference values for frequency volume chart and uroflowmetry parameters in adolescent and adult enuresis patients

Reference values of Frequency Volume Chart (FVC) and uroflowmetry parameters for adolescent and adult enuresis patients are lacking. In this study, we aim to describe those parameters, in order to interpret findings from FVCs and uroflowmetries in those patients. Retrospective, descriptive cohort study, concerning 907 patients aged 11 years and older, suffering from enuresis of at least one wet night per fortnight, treated in a secondary/tertiary centre, between 2003 and 2013. The main FVC parameters of interest were: maximum voided volume (MVV), 24 hr urine production and nocturnal urine volume (NUV) including first morning void (FMV). Nocturnal polyuria (NP) was defined based on both International Children's Continence Society (ICCS, 2014) and International Continence Society (ICS, 2002) definitions. Data of all patients were collected from the medical files. Age had an impact on diurnal and nocturnal FVC parameters. Median MVV excluding FMV was 250 ml in the youngest, 11-year-old males and 363 ml in the eldest, ≥18-yr-old males. For females, these values were 230 ml and 310 ml. Median 24 hr urine production increased from 1,025 ml to 1,502 ml (males) and from 1,007 ml to 1,557 ml (females). Median NUV showed an increase from 387 ml to 519 ml (males) and from 393 ml to 525 (females). Forty-two percent of men and 30% of women had a small MVV (for age). Prevalence of NP differed when assessed by the ICS or the ICCS definition: following ICS guidelines, NP was present in 96% of our male and 93% of our female population, compared to 27% and 41%, respectively, following ICCS guidelines. Both small MVV and NP were found frequently in our adolescent and adult enuresis patients, which is in line with the current thoughts on causal factors. NP prevalence is quite different when using ICS or ICCS definitions, respectively. We would like to encourage the development of an unambiguous definition of NP to use both in pediatric and adult urology. Neurourol. Urodynam. 36:463-468, 2017. © 2016 Wiley Periodicals, Inc.

Clinical efficacy and safety of doxazosin combined with desmopressin in treatment of nocturia in patients with benign prostatic hyperplasia

Thirty six patients aged 50-70 years with benign prostatic hyperplasia (BPH) received doxazosin and desmopressin treatment for 4 weeks. After treatment the International Prostate Symptom Scores (IPSS)and Quality of Life (QoL) scores of patients were significantly improved (17.4±2.5 vs. 11.8±1.1 and 3.9±0.6 vs. 1.8±1.3, respectively; both P<0.01). The nocturia frequency was decreased from 4.6±1.5 to 2.1±1.6 (P<0.01); nocturnal urine output from (564±73) to (348±45) ml (P<0.05); the hours of undisturbed sleep increased from (88.6±17.5)min to (146.2±12.8)min (P<0.05). There were no significant differences in serum levels of sodium, potassium and chlorine, and osmoticpressure before and after treatment. The results indicate that doxazosin combined with desmopressin is safe and effective for treatment of nocturia in patients with BPH. Key words: Deamino arginine vasopressin; Nocturia; Prostatic hyperplasia

Prevalence of Sleep Disordered Breathing among Patients with Nocturia at a Urology Clinic.

We assessed the prevalence of sleep disordered breathing (SDB) and characteristics among patients who visited a urology clinic complaining of nocturia (URO group) and those who visited a sleep apnea (SA) clinic complaining of excessive daytime sleepiness (EDS) (SA group). Additionally, we evaluated the effects of continuous positive airway pressure (CPAP) therapy in the URO group patients with nocturia and SDB resistant to conventional therapy for nocturia. Questionnaires were used to assess EDS, nocturia and lower urinary tract symptoms in 34 URO group patients and 49 age-matched SA group patients. We also compared these factors in the male patients in both groups and the male and female patients in the SA group. Significant SDB was diagnosed as a 3% oxygen desaturation index (3%ODI) on pulse oximeter of >5/h. The treatment response was analyzed in six URO group patients treated with CPAP after not responding to the conventional medical treatment. SDB was found in 91.8% of the SA group patients and 70.6% of the URO group patients. The level of EDS and lower urinary tract symptoms were similar in both groups. The SA group showed higher 3%ODI values, while the frequency of urination during bedtime was higher in the URO group. The frequency of nocturnal urination was reduced after CPAP in the subjects resistant to conventional therapy. SDB is as prevalent in patients who visit a urology clinic complaining of nocturia as in those who visit a sleep apnea clinic. Patients who complains of nocturia must be assessed for SDB before starting therapy for nocturia.

An Exploratory Analysis of the Role of Cue-Induced Urinary Urges in Nocturia

ABSTRACTObjective: The present study assessed the relationship between nocturia and cue-induced urinary urges.Methods: Three hundred and six participants (201 females) ranging from 24 to 88 years of age, median age 53 years old participated in an online survey about bladder symptoms and cues related to urinary urge and urgency incontinence.Results: We found that individuals who experience more instances of cue-related urges have more nocturnal urination, F (4. 504) = 3.106, p < .001, when controlling for age, day time urination frequency, and gender. Our findings suggest that awakening from sleep may be the cause rather than the consequence of urinary urgency.Conclusion: These results add to previous research by offering support that psychological contributors are primary or secondary predictors of urological disorders.

Effect of continuous positive airway pressure on nocturnal urine production in patients with obstructive sleep apnea syndrome.

The aim of this study was to identify the clinical features of patients with obstructive sleep apnea syndrome (OSAS) and investigate the impact of continuous positive airway pressure (CPAP) treatment on nocturnal urine volume. This study enrolled 53 patients with moderate-to-severe OSAS and an apnea-hypoxia index of >20/hr. Data were collected on serum brain natriuretic peptide (BNP) level, International Prostate Symptom Score-Quality of Life (IPSS-QOL) score, Overactive Bladder Symptom Score (OABSS), International Consultation on Incontinence Modular Questionnaire-Nocturia QOL (ICIQ-NQOL) score, Epworth Sleepiness Scale (ESS) score, and the frequency volume chart. Only patients who continued CPAP treatment for 3 months were included in the analysis. In total, 40 patients (33 men and 7 women) completed the study (75.5%). The mean age was 56.9 years. The night-time frequency to void was significantly decreased from 2.1 to 1.2 after CPAP treatment (P < 0.01). The mean scores as assessed by ESS, IPSS-QOL, OABSS, and ICIQ-NQOL significantly improved after CPAP (P < 0.01). The mean diastolic blood pressure significantly decreased after CPAP treatment. However, there was no significant change in the BNP level before and after CPAP treatment. In the frequency volume chart, hours of undisturbed sleep, total nocturnal voided volume, and nocturnal polyuria index significantly improved after CPAP treatment (P < 0.05). However, 24-hr voided volume and mean voided volume during night-time did not change after CPAP treatment. CPAP treatment decreases night-time urinary frequency by reducing nocturnal urine production and improves QOL in patients with OSAS. Neurourol. Urodynam. 36:376-379, 2017. © 2015 Wiley Periodicals, Inc.

Spatiotemporal Regulation of Hematopoietic Stem Cell Niches By Dual Cholinergic Signaling

Hematopoietic stem cells (HSCs) are known to be heterogeneous, but it is unclear whether, or how, different bone marrow (BM) microenvironments can imprint distinct HSC states. In the BM, quiescent HSCs have been found enriched in endosteal niches, whereas activated HSCs traffic in and out the BM through sinusoids localized further from bone. However, how these separate niches are integrally regulated to maintain BM homeostasis remains largely unknown. We have shown previously that sympathetic adrenergic nerve terminals innervating nestin+ mesenchymal stem cells (MSCs) regulate HSC egress from BM to circulation (Méndez-Ferrer S et al, Nature 2008 and 2010). This regulatory network is required to control HSC proliferation and migration, since its damage caused by mutated HSCs can lead to the manifestation of diseases such as myeloproliferative neoplasms and its protection can block the progression of these disorders (Arranz L et al, Nature 2014). Here we aimed to study the possible cooperation of both branches of the autonomic nervous system, the parasympathetic and the sympathetic nervous systems, which have antagonistic actions in other systems, in HSC regulation in endosteal and sinusoidal niches. We describe for the first time different cholinergic neural signals derived from both autonomic branches that regulate spatially and temporally distinct BM HSC niches. We used mice deficient in cholinergic nerve fibers (secreting acethylcholine, the main postsynaptic neurotransmitter of the parasympathetic nervous system), due to the lack of the neurturin receptor Gfrα2, a member of the glial-cell-derived family of neurotrophic factors (Rossi J et al. Neuron 1999). We found that Gfrα2-/- mice exhibited a circadian-specific defect in HSC traffic. Parasympathetic deficiency caused exacerbated sympathetic tone, manifested by ~2-fold increased BM sympathetic adrenergic fibers and nocturnal urine norepinephrine. Circulating HSCs, measured by long-term competitive repopulating assays, were 3-fold higher in Gfrα2-/- mice only during the resting period, and this was rescued by deletion of the β3-adrenergic-receptor. Therefore, systemic parasympathetic cholinergic signals antagonize BM sympathetic adrenergic activity during the resting phase, contributing to β3-adrenergic-receptor-orchestrated circadian HSC traffic through sinusoidal niches. On the other hand, sympathetic cholinergic nerve fibers, described here for the first time in the BM and running along Haversian canals of bone, regulate HSC maintenance and quiescence in endosteal niches. In neonatal mice, we found that some endosteal sympathetic nerve fibers, sensitive to chemical sympathectomy by 6-hydroxydopamine, switch from catecholaminergic to cholinergic fate and help direct developmental HSC migration to BM. This migration, dependent in perinatal life on Cxcl12 produced by BM nestin+ MSCs (Isern et al, eLife 2014), was impaired in Gfrα2-/- mice, which exhibited one week after birth a reversible ~40% reduction in BM HSCs, associated with the lack of BM sympathetic cholinergic fibers. In adult mice, these sympathetic cholinergic fibers activate nicotinic receptors and induce Cxcl12 expression in bone-associated nestin+ MSCs, an effect reproduced in vitro with the MS-5 stromal cell line. Cxcl12 expression was 2.5-fold higher in Nes-GFP+ cells associated with the bone, compared with those that were not, and was 4-fold lower in Gfrα2-/- Nes-GFP+ cells localized only in the endosteal BM. Concomitantly, Gfrα2-/- mice exhibited reduced allocation of quiescent HSPCs in the endosteal BM, compared with control mice, in which the HSPC fraction in the G0 cell cycle phase was 2-fold higher in the endosteal than in non-endosteal BM. Moreover, HSCs from Gfrα2-/- mice showed increased proliferation, even 6 months after transplantation into secondary wild-type recipients. As a result, Gfrα2-/- mice exhibit accelerated hematopoietic recovery after myeloablation, a phenotype mimicked by mice deficient in the α7-nicotinic receptor. Increased HSC proliferation was associated with loss of self-renewal, since bone-associated HSCs from Gfrα2-/- mice exhibited 50% reduced reconstituting capacity and myeloid potential 24 weeks after competitive transplantation into wild-type recipients. Thus, both branches of the autonomic nervous system regulate HSC maintenance and function in temporally and spatially separate niches. DisclosuresNo relevant conflicts of interest to declare.

Effects of desmopressin for the treatment of nocturnal polyuria in elderly women: impact on related sleep quality.

We investigated the efficacy, safety, and impact of desmopressin on quality of sleep in treating nocturnal polyuria in elderly women. We recruited 60 women over 60 years old with lower urinary tract symptoms (LUTS), including nocturia, and with nocturnal polyuria. Nocturnal polyuria was defined as nighttime urine production exceeding 33% of the 24-hour total urine volume determined by a frequency volume (FV) chart. All patients failed to respond to treatment of their underlying disease and evening fluid restriction. Desmopressin 0.1 mg was administered orally at bedtime for 12 weeks. The participants completed a series of questionnaires on the Medical Outcomes Study (MOS) sleep scale and FV chart before and after treatment. The patient population had a mean age of 69.2 ± 9.4 years (range: 61-81). The mean duration of symptoms was 61.2 ± 45.1 months. Significant decreases were evident after desmopressin treatment in the number of nocturia episodes (3.63 ± 1.61 to 2.00 ± 1.13, p = 0.01), nocturnal urine volume (p = 0.01), nocturnal polyuria index (NPI) (p = 0.01), and nocturia index (NI) p = 0.01). Among the categories of the MOS sleep scale, sleep index (p = 0.003), sleep disturbance (p = 0.001), snoring (p = 0.028), and shortness of breath (p = 0.036) significantly changed, with a decreased number of nocturia episodes. Adverse events were mild. Desmopressin is an effective treatment for nocturnal polyuria in elderly women, where conservative treatment has failed. Sleep quality is also improved.

Impact of multicomponent, nonpharmacologic interventions on perioperative cortisol and melatonin levels and postoperative delirium in elderly oral cancer patients

ObjectiveTo investigate the impact of multicomponent, nonpharmacologic interventions (MNI) on perioperative cortisol and melatonin levels, as well as postoperative delirium (PD), in elderly oral cancer patients. MethodsA total of 160 elderly oral cancer patients who underwent tumor resection surgery and completed our investigation were included in this study. The cancer patients were randomly divided into 2 groups: Group U or Group I. During the perioperative period, Group U received usual care, while Group I received MNI, which is based on usual care and aims to decrease the risk of PD. MNI focused on general geriatric approaches and supportive nursing care. On the day before surgery and the first three postoperative days, nocturnal (20:00–8:00) urine samples were collected. The melatonin sulfate and cortisol levels in the urine samples were determined. Moreover, the RASS (Richmond Agitation Sedation Scale), CAM-ICU (Confusion Assessment Method for the Intensive Care Unit) and QoR40 (40-item quality of recovery score) scores were dynamically monitored. ResultsThere were no significant differences in the general characteristics between the 2 groups. After surgery, the melatonin sulfate levels in the nocturnal urine of Group I were higher than those in Group U. The cortisol concentrations were lower in Group I compared to those in Group U. Group I achieved better postoperative RASS and QoR40 scores than Group U. Compared to Group U, Group I also experienced less PD (incidence and duration). ConclusionsMNI ameliorated some postoperative disturbances regarding sleep and stress, decreased the incidence of PD and improved recovery quality.

Indoor cold exposure and nocturia: a cross-sectional analysis of the HEIJO-KYO study.

To investigate the association between indoor cold exposure and the prevalence of nocturia in an elderly population. The temperature in the living rooms and bedrooms of 1 065 home-dwelling elderly volunteers (aged ≥60 years) was measured for 48 h. Nocturia (≥2 voids per night) and nocturnal urine production were determined using a urination diary and nocturnal urine collection, respectively. The mean ± sd age of participants was 71.9 ± 7.1 years, and the prevalence of nocturia was 30.8%. A 1 °C decrease in daytime indoor temperature was associated with a higher odds ratio (OR) for nocturia (1.075, 95% confidence interval [CI] 1.026-1.126; P = 0.002), independently of outdoor temperature and other potential confounders such as basic characteristics (age, gender, body mass index, alcohol intake, smoking), comorbidities (diabetes, renal dysfunction), medications (calcium channel blocker, diuretics, sleeping pills), socio-economic status (education, household income), night-time dipping of ambulatory blood pressure, daytime physical activity, objectively measured sleep efficiency, and urinary 6-sulphatoxymelatonin excretion. The association remained significant after adjustment for nocturnal urine production rate (OR 1.095 [95% CI 1.042-1.150]; P < 0.001). Indoor cold exposure during the daytime was independently associated with nocturia among elderly participants. The explanation for this association may be cold-induced detrusor overactivity. The prevalence of nocturia could be reduced by modification of the indoor thermal environment.

Nocturnal Polyuria: Excess of Nocturnal Urine Production, Excess of Definitions—Influence on Renal Function Profile

This study aimed to identify important differences in renal function profile, and potential water and sodium diuresis cutoffs among participants with nocturnal polyuria according to nocturnal polyuria definitions. This post hoc analysis was based on a prospective study in which participants completed a bladder diary, collected urine and provided a blood sample. With an age dependent nocturnal polyuria index greater than 20% to 33% as the referent 4 definitions of nocturnal polyuria were compared, including 1) nocturnal polyuria index greater than 33%, 2) nocturnal urine production greater than 90 ml per hour and 3) greater than 10 ml/kg, and 4)nocturia index greater than 1.5. In 112 male and female participants significant differences in baseline characteristics and bladder diary parameters were found according to definition. Diuresis rate, free water clearance and sodium clearance had similar 24-hour courses in the subgroups with and without polyuria by each definition. The range varied more in the subgroup with vs without polyuria, especially at night for diuresis rate and free water clearance. At night the latter decreased in the polyuria subgroup based on each definition (p <0.001 to 0.045). A significant difference vs the no polyuria subgroups was found only for urine production greater than 90 ml per hour and polyuria index greater than 20% to 33%. For each definition sodium clearance remained high in the polyuria subgroup, which differed significantly from the no polyuria subgroups (p <0.001 to 0.030). Free water and sodium clearance cutoffs ranged from -0.65 to -0.85 ml per minute between 12 and 2 a.m., and 0.65 to 0.77 ml per minute between 3 and 5 a.m., respectively, with large sensitivity and specificity differences according to definition. There were important differences when comparing participants with vs without nocturnal polyuria by definition. The renal function profile indicating the pathophysiological mechanism of nocturnal polyuria did not seem to be influenced by definition but free water clearance and sodium clearance cutoff sensitivity differed substantially. These results must be confirmed in a larger homogeneous sample.