Nocturia (>2 per night) is the most frequent cause of disturbed sleep in older people. Poor sleep results in reduced health related QoL, and is linked to the development of cognitive impairment. Nocturia can result in an increase risk of falls and fractures, and is also an independent risk factor for mortality. The prevalence of norturia is high in the elderly, and it has been reported to be around 77.1% in elderly women and 93% in men. Historically, this bothersome symptom is thought to be mainly a result of bladder outflow obstruction due to prostatic hypertrophy or overactive bladder. More recently, nocturia has been associated witsh nocturnal polyuria (NPu) and obstructive sleep apnoea (OSA). The relationship between OSA and NPu is not fully understood but it is thought that the negative intrathoracic pressure generated by OSA causes an increase in Atrial Natriuretic Peptide (ANP) secretion, resulting in NPu. Nocturia is highly prevalent in patients with severe OSA. However, patients are usually unaware that they have sleep apnoea, and are therefore more likely to present to urology or geriatric services. It is important that OSA is not overlooked in these clinics as intervention with CPAP is highly effective in reducing symptoms. Here, we present the result of using the STOP-Bang questionnaire in 71 consecutive patients presenting to our urology service with nocturia. The average age was 73 years (range 34-88), male-to-female ratio 14:1 and median nocturia frequency of 4. 42 patients were at risk of undiagnosed sleep apnoea (median STOP-Bang Score of 5)—35 were referred for sleep studies, 4 patients declined and 3 patients were not referred. Overall, 31 out of 35 sleep studies (88.6%) demonstrated the presence of OSA; of these 23 (74.2%) confirmed moderate or severe OSA. All patients with OSA were seen and treated by the respiratory service. Overall, median nocturia frequency decreased from 4 to 1 across the whole cohort, from a combination of CPAP therapy, bladder outlet procedures and desmopressin. Conclusion At least a third of patients (32%) with bothersome nocturia have an undiagnosed clinically-significant OSA. Identification of OSA improves outcomes across the whole cohort, because nocturia in patients without OSA is more likely to respond to bladder outlet procedures and desmopressin.
Objective: COVID-19 has challenged diagnostic and surveillance pathways for suspected and known bladder transitional cell cancer (TCC). Exclusion of high-grade/invasive TCC by molecular urine testing could risk stratify patients for priority flexible cystoscopy and transurethral resection (TUR). We evaluated ADXBladder (ArquerDx), which has a high negative predictive value (NPV) for high-grade and ⩾ pT1 TCC. Patients and methods: Prospective cohort study of patients referred with haematuria for diagnostics or on TCC surveillance (Dec 2020–Feb 2021). Patients underwent ADXBladder testing, flexible cystoscopy and imaging (for haematuria), followed by TUR/biopsy as necessary. Clinico-radiological/pathology findings were compared with ADXBladder results. Results: Of 117 eligible patients, 39 and 78 had positive and negative ADXBladder tests, respectively. Of 15 suspected TCC on cystoscopy, eight were confirmed on TUR/biopsy. Overall ADXBladder NPV was 96.2% (CI: 91.0–98.4). NPV for high-grade and ⩾pT1 TCC was 97.4% (CI: 94.4–98.8) and 98.7% (CI: 95.0–99.7), respectively. Conclusions: Our ‘real world’ evaluation confirmed a high NPV for high grade and ⩾pT1 TCC using ADXBladder. Further larger studies are required to determine whether a negative ADXBladder test combined with negative imaging and patient risk factors may justify patient downgrading on timed diagnostic pathways. Level of evidence: IV
341 Ex vivo expansion of cord blood mononuclear cells (CBMNCs) could provide a safe, flexible and ample supply of blood components for cellular therapies. Traditionally, hematopoietic cell expansion has been performed in 2D tissue culture flask or well-plate static cultures using abnormally high concentrations of cytokines which is expensive, reduces the self-renewal capacity, and skews normal differentiation. We have previously developed a 3D bone marrow biomimicry through the use of a synthetic scaffold made of polyurethane (PU) coated with collagen type I which could expand CBMNCs in a cytokine-free environment for at least 28 days ex vivo, with or without the addition of serum to the media. We hypothesised that the addition of near physiological concentrations (0.2U/mL and 1.845U/mL) of exogenous erythropoietin (EPO) to these established 3D CBMNC ex vivo cultures at day 14 in a serum-free and cytokine-free environment would be sufficient to enhance erythropoiesis. CBMNCs were separated by Ficoll-Paque density gradient and seeded onto collagen-coated PU 3D scaffolds at a cell density of 2.5×106cells per scaffold (5×5×5mm3). Cultures were established in serum-free conditions and only EPO was added at days 14–28, with full-medium exchange every 2 days. Culture output was evaluated at days 14, 21 and 28 both by physically extracting cells from the scaffolds and by in situ analysis. Over 28 days, most stages of maturation, from erythroid progenitors to enucleated erythrocytes were observed by light microscopy of cytospins and by immunophenotypic analysis of extracted cells (CD45−/CD71+/CD235+), with more maturation occurring by day 28 of culture, after the addition of EPO. Although both concentrations of EPO produced comparable erythroid differentiation of cells, even by CFU assay, the viability (75% vs. 61%, p<0.05) and proliferative capacity at day 28 of culture was enhanced in the higher concentration of EPO compared with that in the lower concentration (p<0.05). In contrast, standard 2D control cultures (without serum or cytokines) collapsed within 5 days. In situ, scanning electron microscopy showed maturation of erythrocytes within central sections of the scaffolds to enucleation by day 28 and multiphoton microscopy confirmed the presence of structures resembling erythroid islands as early as day 14 of culture, prior to the addition of EPO. In conclusion, 3D PU-collagen scaffolds may provide a good model to study erythropoiesis ex vivo, using physiological concentrations of EPO, and has the potential to expand red cells in response to higher levels of exogenous EPO in a culture system that would be suitable for clinical applications. Disclosures: No relevant conflicts of interest to declare.
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