Prevalence of Sleep CALM nocturia factors in a male veteran population.

INTRODUCTION: Nocturia is a complex and multifactorial condition, associated with several genitourinary abnormalities as well as a host of conditions beyond the urinary tract, and thus often poses a significant diagnostic challenge in real-world practice. Sleep Disorders, Comorbidities, Actions, Lower Urinary Tract Dysfunction, and Medications, the so-called "Sleep C.A.L.M." factors, are five common causes of nocturia requiring judicious evaluation according to current consensus guidelines. This study aims to assess the prevalence of the Sleep C.A.L.M. factors in a nocturia clinical population. METHODS: Retrospective analysis of frequency-volume charts from men with ≥2 nocturnal voids as well as concurrent demographic, clinical, and medical history data to identify patients with each of the Sleep C.A.L.M. FACTORS: Comorbidities and medications were classified as a single group. RESULTS: A total of 213 subjects met the criteria for inclusion (median age 68.0 [63.5-75.5] years). The prevalence of 1) sleep disorders, 2) comorbidities and/or medication use, 3) actions (i.e., modifiable behaviors/lifestyle factors), and 4) lower urinary tract dysfunction was 31%, 31%, 19%, and 41%, respectively. Among included participants, 73% were found to have at least 1 Sleep C.A.L.M. factor, and 33% had multiple Sleep C.A.L.M. FACTORS: Results were similar upon stratification by age and nocturnal polyuria status. CONCLUSIONS: The Sleep C.A.L.M. factors are highly common among nocturia patients in the clinical urology setting. Although many of these factors are strongly associated with advanced age in community-based nocturia study samples, they appear common even among younger men in a nocturia patient population; the differential effect of age and individual Sleep C.A.L.M. factors on nocturia pathophysiology requires further investigation.

How do we make progress in phenotyping patients with lower urinary tract such as overactive bladder and underactive detrusor, including using urine markers and microbiome data, to personalize therapy? ICI-RS 2023-Part 2.

INTRODUCTION: Overactive bladder (OAB) and underactive bladder (UAB) could be associated with metabolic syndrome, affective disorders, sex hormone deficiency, changes in urinary microbiota, functional gastrointestinal disorders, or autonomic nervous system dysfunction. OBJECTIVES: The aim of this Think Tank was to provide a guide on how to investigate OAB and/or detrusor underactivity (DU) patients to better clarify the underlying pathophysiology and possibly personalize the treatment. METHODS: A compendium of discussion based on the current evidence related to phenotyping patients with OAB or DU using urodynamic tests, functional neuro-imaging, urinary markers, and microbiome. RESULTS AND CONCLUSIONS: The article emphasizes the critical significance of adopting a comprehensive yet tailored approach to phenotyping patients with lower urinary tract (LUT) symptoms, such as OAB and UAB. The intricate interplay between the LUT and various factors, metabolic, neurological, psychological, and gastrointestinal can define unique LUT profiles, enabling personalized therapies to replace the one-size-fits-all approach.

How do we make progress in phenotyping patients with LUT such as OAB and underactive detrusor, including using urine markers and microbiome data, in order to personalize therapy? ICI-RS 2023: Part 1.

INTRODUCTION: Overactive bladder (OAB) and Underactive bladder (UAB) could be associated with metabolic syndrome, affective disorders, sex hormone deficiency, changes in urinary microbiota, functional gastrointestinal disorders, or autonomic nervous system dysfunction. OBJECTIVES: The aim of this Think Tank was to provide a guide on how to investigate OAB and/or detrusor underactivity (DU) patients to better clarify the underlying pathophysiology and possibly personalize the treatment. METHODS: A compendium of discussion based on the current evidence related to phenotyping patients with OAB or DU investigating metabolic, neurogical, psychological and gastrointestinal aspects with the aim to personalize the treatment. RESULTS AND CONCLUSIONS: The article emphasizes the critical significance of adopting a comprehensive yet tailored approach to phenotyping patients with lower urinary tract symptoms, such as OAB and UAB. The intricate interplay between the lower urinary tract and various factors, metabolic, neurological, psychological, and gastrointestinal can define unique LUT profiles, enabling personalized therapies to replace the one-size-fits-all approach.

Introductory editorial: Lifelong LUTS, a matter of transition?

INTRODUCTION: The EPIC study has highlighted the prominence of nocturia as a crucial symptom of overactive bladder (OAB), intertwining OAB and nocturia with bladder, kidney, and brain functions. METHODS: Expert opinion, review. RESULTS: To truly comprehend lower urinary tract symptoms (LUTS), we must delve into the interactions among these three systems, alongside their circadian rhythms. CONCLUSION: The perception of LUTS is a result of the intricate interplay between bladder, brain, and kidney function, which may evolve across a lifetime due to the (dys)functionality of these organs.

Exploring lifelong overactive bladder: Transitions, evidence, and clinical implications; A modified Delphi process.

INTRODUCTION: Overactive bladder (OAB) is a prevalent urological condition characterized by urinary urgency, with or without urgency urinary incontinence, accompanied by increased daytime frequency and nocturia. However, the current definition of OAB lacks a specified time frame, hindering our understanding of the temporal aspects and transitions that occur within the OAB spectrum. METHODS: A modified Delphi study was conducted in three rounds, involving a panel of international experts in functional urology, urogynaecology, geriatrics, transitional medicine, and pediatric urology. The study took place between February 2023 and June 2023 and employed two sequential rounds of online surveys, followed by a final hybrid group discussion session in June 2023. RESULTS: The Delphi process resulted in a consensus definition of lifelong OAB as a persistent and continuous condition that may manifest differently from birth and evolve over time, with varying levels of clinical perception. The course of its progression is influenced by transition periods and modifying factors, mainly anatomical, hormonal, and psychosocial/stressors. Three main transition periods were identified: achievement of daytime continence, adulthood to elderly, and transition to frail elderly. The panel also considered the therapeutic and diagnostic implications of lifelong OAB, as well as future research prospects in terms of importance and feasibility. CONCLUSIONS: Future longitudinal research is needed to develop this concept and further identify transitions and temporal dynamics.

Is the insomnia phenotype the common denominator in LUTS during transition periods? An expert NOPIA research group review.

AIMS: As people age, sleep stages and characteristics transition over time, but sleep deficits can profoundly impact health and cognitive functioning. Chronic sleep deprivation is linked to impaired attention and productivity, weakened immunity, increased risk of cardiovascular disease, obesity, and mental health disorders. Insomnia, obstructive sleep apnea syndrome, hormonal changes, nocturia, neurological disorders, and life events interfere with sleep patterns and some are linked to lower urinary tract symptoms (LUTS). This NOPIA symposium on Lifelong LUTS aimed to analyze the literature on associations between sleep and LUTS, generate ideas for future research, and explore whether there is support for the concept of lifelong LUTS in relation to changes in sleep throughout the lifespan. METHODS: An international panel of experts took part in an online meeting addressing the role of lifelong LUTS in relationship to sleep and the brain organized by the NOPIA research group. The manuscript summarizes existing literature, hypotheses, future research ideas, and clinical recommendations. RESULTS: Insomnia, sleep fragmentation, hyperarousal, and sensory processing disorders emerged as potential factors in the relationship between sleep and LUTS. Insomnia is often a persistent factor and may have been the initial symptom; however, it is often unrecognized and/or unaddressed in healthcare settings. By recognizing insomnia as a primary driver of various health issues, including nocturia, transitional care aims to address root causes and underlying problems earlier to initiate appropriate treatment. CONCLUSIONS: A multidisciplinary approach with collaboration between healthcare professionals from various disciplines, such as urology, sleep medicine, gynecology, pediatrics, and geriatrics, is needed and should include validated measurements such as the insomnia severity index and sleep and voiding diaries. Ensuring ongoing follow-up and monitoring through transitional care is crucial for individuals with persistent sleep problems and LUTS, allowing issues that arise or fluctuate over the lifespan to be addressed.

The role of renal circadian biorhythms in lifelong LUTS.

INTRODUCTION: This article delves into the intricate relationship between kidney function, diuresis, and lower urinary tract symptoms (LUTS) throughout the transitions of the human lifespan. It explores circadian regulation of urine production, maturation of renal function from birth to adulthood, and effects of aging on kidney function and LUTS. The complex connections between these factors are highlighted, offering insights into potential interventions and personalized management strategies. METHODS: An international panel of seven experts engaged in online discussions, focusing on kidney function, diuresis, and LUTS throughout life. This manuscript summarizes expert insights, literature reviews, and findings presented during a webinar and subsequent discussions. RESULTS: Renal function undergoes significant maturation from birth to adulthood, with changes in glomerular filtration rate, diuresis, and tubular function. A circadian rhythm in urine production is established during childhood. Adolescents and young adults can experience persistent enuresis due to lifestyle factors, comorbidities, and complex physiological changes. In older adults, age-related alterations in kidney function disrupt the circadian rhythm of diuresis, contributing to nocturnal polyuria and LUTS. CONCLUSION: The interplay between kidney function, diuresis, and LUTS is crucial in understanding lifelong urinary health. Bridging the gap between pediatric and adult care is essential to address enuresis in adolescents and young adults effectively. For older adults, recognizing the impact of aging on renal function and fluid balance is vital in managing nocturia. This holistic approach provides a foundation for developing innovative interventions and personalized treatments to enhance quality of life for individuals with LUTS across all stages of life.

Urinary bladder phantom mimicking mechanical properties and pressure during filling.

Objective.Phantoms that mimic healthy or diseased organ properties can complement animal models for surgical planning, training, and medical device development. If urodynamic studies rely on pressure-volume curves to assess lower urinary tract symptoms, there is an unsatisfied need for a bladder phantom that accurately mimics the bladder stretching capabilities and compliant behaviour during physiological filling.Approach.We demonstrate the suitability of water-soluble 3D-printed moulds as a versatile method to fabricate accurate phantoms with anatomical structures reconstructed from medical images. We report a phantom fabricated with silicone rubber. A wire net limits the silicone expansion to model the cystometric capacity. A mathematical model describes the pressure increase due to passive hyperelastic properties.Main results.The phantom reproduces the bladder's mechanical properties during filling. The pressure-volume curve measured on the phantom is typical of cystometric studies, with a compliance of 25.2 ± 1mlcmH2O-1.The root-mean-square error between the theoretical model and experimental data is 2.7cmH2O.The compliance, bladder wall thickness, cystometric capacity and pressure near the cystometric capacity of the phantom can be tuned to mimic various pathologies or human variability.Significance.The manufacturing method is suitable for fabricating bladder and other soft and hollow organ phantoms. The mathematical model provides a method to determine design parameters to model healthy or diseased bladders. Soft hollow organ phantoms can be used to complement animal experimentations for developing and validating medical devices aiming to be anchored on these organs or monitor their activity through pressure and strain measurement.

'Nocturomics': transition to omics-driven biomarkers of nocturia, a systematic review and future prospects.

OBJECTIVE: To systematically review studies that investigated different biomarkers of nocturia, including omics-driven biomarkers or 'Nocturomics'. MATERIALS AND METHODS: PubMed® , Scopus® , and Embase® were searched systematically in May 2022 for research papers on biomarkers in physiological fluids and tissues from patients with nocturia. A distinction was made between biomarkers or candidates discovered by omics techniques, referred to as omics-driven biomarkers, and classical biomarkers, measured by standard laboratory techniques and mostly thought from pathophysiological hypothesis. RESULTS: A total of 13 studies with 18 881 patients in total were included, eight of which focused on classical biomarkers including: atrial natriuretic peptide (ANP), B-type natriuretic peptide (BNP), C-reactive protein (CRP), aldosterone, and melatonin. Five were 'Nocturomics', including one that assessed the microbiome and identified 27 faecal and eight urinary bacteria correlated with nocturia; and four studies that identified candidate metabolomic biomarkers, including fatty acid metabolites, serotonin, glycerol, lauric acid, thiaproline, and imidazolelactic acid among others. To date, no biomarker is recommended in clinical practice. Nocturomics are in an embryonic phase of conception but are developing quickly. Although candidate biomarkers are being identified, none of them are yet validated on a large sample, although some preclinical studies have shown a probable role of fatty acid metabolites as a possible biomarker of circadian rhythm and chronotherapy. CONCLUSION: Further research is needed to validate biomarkers for nocturia within the framework of a diagnostic and therapeutic precision medicine perspective. We hope this study provides a summary of the current biomarker discoveries associated with nocturia and details future prospects for omics-driven biomarkers.

CAR-T Cell Therapy for Solid Tumors: Are we Still That Far? a Systematic Review of Literature.

This systematic review aims to assess all the prospective studies published to date on the efficacy of CAR-T cell therapy in solid tumors. Databases searched were PubMed and Google Scholar from inception through May 1st 2021. Search query was (Chimeric antigen receptor) or (CAR-T) or (T-CAR). Twenty-nine prospective studies (265 patients) were included. Most published clinical trials are phase I. Clinical benefit was 100% in epithelial ovarian cancer, 70-82% in gastrointestinal tumors, 79% in mesothelioma, 63% in small-cell lung cancer, 24-67% in sarcoma, 50-62% in prostate cancer, and 45-50% in central nervous system tumors. No serious CAR-T cell specific serious toxicities were noted.

Intra-Cavernosal Injection of Botulinum Toxin in the Treatment of Erectile Dysfunction: a Systematic Review and Meta-Analysis.

OBJECTIVE: To evaluate the role of botulinum toxin in treating erectile dysfunction as a novel treatment strategy avoiding morbid and irreversible surgeries. METHODS: A systematic review of literature was conducted from January 1990 through July 31, 2021. Search engines used included PubMed, Embase and Medline databases, to identify studies investigating botulinum toxin in erectile dysfunction, published in English. Seven studies in total were included in our review including two pre-clinical studies. A meta-analysis was performed on three outcomes included commonly in at least two studies. Among the different parameters assessed were, Erection Hardness Score (EHS), Peak Systolic Velocity in cavernosal artery (PSV) and the Sexual Health Inventory for Men (SHIM) score. RESULTS: A clear benefit was noted for intracavernosal injection (ICI) of botulinum toxin (BoNT-A) on PSV with a mean difference (MD) of 10.82 [4.99, 16.65] and a heterogeneity of I2=61%. EHS results favored BoNT-A as well over placebo with a MD of 0.7 [0.47, 0.93] and heterogeneity of I2=94%. As for SHIM score, with a heterogeneity of I2=85%, no statistically significant difference was found (MD 0.58 [-0.03, 1.20]). CONCLUSION: Our review and meta-analysis have shown statistical significance for the benefit of BoNT-A in terms of EHS and PSV. However, this statistical significance should be interpreted in light of the given limitations: small sample size, heterogeneity in data collection, patient selection bias, and clinical significance of the measured differences. ICI of BoNT-A should currently be limited to clinical studies to further elucidate its clinical benefit.

OAB supraspinal control network, transition with age, and effect of treatment: A systematic review.

OBJECTIVE: In light of a better understanding of supraspinal control of nonneurogenic overactive bladder (OAB), the prevalence of which increases with age, functional imaging has gained significant momentum. The objective of this study was to perform a systematic review on the transition of supraspinal control of OAB with age, the effect of therapeutic modalities, and a coordinate-based meta-analysis of all neuroimaging evidence on supraspinal OAB control in response to bladder filling. METHODOLOGY: We performed a systematic literature search of all relevant libraries in November 2021. The coordinates of brain activity were extracted from eligible neuroimaging studies to perform an activation likelihood estimation (ALE) meta-analysis. RESULTS: A total of 16 studies out of 241 were selected for our systematic review. Coordinates were extracted from five experiments involving 70 patients. ALE meta-analysis showed activation of the insula, supplementary motor area, dorsolateral prefrontal cortex, anterior cingulate gyrus, and temporal gyrus with a transition of activation patterns with age, using a threshold of uncorrected p < 0.001. Among young patients, neuroplasticity allows the activation of accessory circuits to maintain continence, as in the cerebellum and temporoparietal lobes. Anticholinergics, pelvic floor muscle training, sacral neuromodulation, and hypnotherapy are correlated with supraspinal changes attributed to adaptability and possibly a substratum of an intrinsic supraspinal component. The latter is better demonstrated by a resting-state functional connectivity analysis, a promising tool to phenotype OAB with recent successful models of predicting severity and response to behavioral treatments. CONCLUSION: Future neuroimaging studies are necessary to better define an OAB neurosignature to allocate patients to successful treatments.

Uncovering the role of urinary microbiota in urological tumors: a systematic review of literature.

PURPOSE: Urinary microbiota has been found to play a key role in numerous urological diseases. The aim of this systematic review is to depict the role of urinary microbiota in the pathogenesis, diagnosis, prognosis, and treatment of urological tumors, including bladder cancer (BCa), prostate cancer (PCa) and renal cell carcinoma (RCC). METHODS: A systematic PubMed and Scopus search was undergone from inception through June 2021 for studies investigating urinary microbiota alterations in urological tumors. Study selection followed the PRISMA statement. Phylum, family, genus and species of each bacterium in cancer patients and controls were recorded. RESULTS: Twenty-one studies with 1194 patients (748 cancer patients and 446 controls) were included in our final analysis. Certain bacterial phylum, family, genus, and species were more predominant in each of BCa, PCa and RCC patients compared to controls. Abundance and specificity of urinary microbiota were prognosticators for: (1) recurrence, distinguishing recurrent from non-recurrent BCa, (2) disease stage, distinguishing non-muscle invasive from muscle invasive BCa, and (3) disease grade, distinguishing high- vs. low-grade PCa and BCa. Dietary, environmental and geographic patterns influenced urinary microbiota. Urinary microbiota of benign prostatic hyperplasia was different from PCa. CONCLUSION: Urological cancer patients have an altered urinary microbiota compared to controls. This may predict recurrence, disease stage and disease grade of these tumors. Further prospective studies are needed to depict a potential influence on therapeutic outcomes.

A dynamic online nomogram predicting severe vitamin D deficiency at ICU admission.

INTRODUCTION: Although prevalent and associated with worsened outcomes, vitamin D severe deficiency is not systematically searched among intensive care unit (ICU) admissions and waiting time for measurement results range from hours to few days. Hence, we developed and internally validated a simple nomogram for predicting severe vitamin D deficiency at ICU admission. PATIENTS AND METHODS: Data of 3338 ICU admissions from an observational prospective cohort registered between January 2017 and December 2019 were analyzed. Demographic data as well as severity scores and season of admission were obtained. After splitting the population into training and test sets, a least absolute shrinkage (LASSO) regression model was used to select factors and construct the nomogram. Calibration and discrimination were used to assess the nomogram performance. Clinical use was evaluated by a decision curve analysis. RESULTS: Age, gender, Sequential Organ Failure Assessment (SOFA), Simplified Acute Physiology Score III (SAPS3) and season of admission were identified by the LASSO regression analysis as significant predictors of vitamin D severe deficiency at ICU admission. The nomogram model showed good discrimination with a 1000 bootstrap analysis and good calibration with a C-index of 0.64. The decision curve analysis showed that at a threshold probability between 30% and 50%, using the nomogram adds more benefit that considering that all patients are severely deficient or non-severely deficient. CONCLUSIONS: This easy-to-use dynamic nomogram can help physicians to select patients that could benefit the most from vitamin D supplementation at ICU admission. External validation is needed to verify the generalizability of this nomogram.

A systematic review of imaging-guided metastasis-directed therapy for oligorecurrent prostate cancer: revolution or devolution?

INTRODUCTION: Metastasis directed therapy (MDT) is increasingly being implemented in recurring prostate cancer (PCa), although its role in PCa management has yet been fully defined. Aim of the current systematic review is to analyze current knowledge of MDT in the setting of recurrent PCa and highlight future trials which will continue to shed a light on a controversial aspect of current PCa management. EVIDENCE ACQUISITION: The National Library of Medicine Database was searched for relevant articles published between January 2014 and August 2019. A wide search was performed including the combination of following words: ([metastasis AND directed AND therapy] AND prostate AND cancer). The selection procedure followed the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) principles. EVIDENCE SYNTHESIS: Biologic studies support the use of MDT in oligometastatic PCa. Modern imaging techniques as PSMA PET/CT, Fuciclovine PET/CT and whole-body MRI are fundamental to implement such an approach given the high diagnostic yield at low PSA values. The majority of data available on MDT concerns retrospective trials, although three prospective randomized trials (STOMP, ORIOLE and POPSTAR) have assessed the safety and feasibility of MDT. Overall, it appears that MDT delays significantly PCa progression and time to systemic therapy. CONCLUSIONS: MDT is highly appealing given its potential to delay disease progression and adverse events of systemic therapy. Nonetheless, data remains immature to recommend MDT on a large scale and the selection criteria for patients have yet been defined. Today, MDT should be administered within a clinical trial and results of future research are eagerly awaited.