A Pilot Study of Functional Brain Magnetic Resonance Imaging in BPS/IC Patients: Evidence of Central Sensitization.

Bladder pain syndrome/Interstitial cystitis (BPS/IC) is characterized by increased activity in bladder afferent pathways, recruitment of silent nociceptive neurons, and sensitization of the brain areas responsible for pain amplification. Default mode network (DMN) is a set of regions activated during the resting state, which reflect the brain's intrinsic activity. Conversely, the sensorimotor network (SMN) plays a key role in structural neuroplasticity. This study aimed to evaluate DMN and SMN activity in BPS/IC patients, both with and without bladder noxious stimulus, using functional brain magnetic resonance imaging (MRI). Six BPS/IC female patients underwent 3 Tesla fMRI brain scanners. Acquisitions consisted of 10-minute blood oxygen level-dependent echo-planar imaging. The first acquisition was with an empty bladder, painless, and the second was with suprapubic pain. Data were processed using the independent component analysis method with the MELODIC tool from the functional brain MRI of the Brain Software Library (FSL). A semi-quantitative analysis was performed afterward. The patients' age was 42.6 ± 5 years, pain intensity was 7 ± 0.7 (0-10), day and night frequency were 9.2 ± 2.2 and 2.8 ± 1.0, and maximal bladder capacity was 260 ± 54 mL. One patient was unable to complete the study. All patients showed a comparable DMN activation in both empty and full bladder states, and all presented high SMN activation whether the bladder was empty or full. The activation of DMN at both bladder states, empty and full, and constant SMN activation without and with pain supports the role of these networks in BPS/IC. Similar findings have been reported in other chronic pain syndromes.

Symptom flares in women with chronic pelvic pain: Questionnaire study within a cohort study (translational research in pelvic pain (TRiPP)).

OBJECTIVE: To quantify the variation, triggers and impact on quality of life of symptom flares in women with chronic pelvic pain (CPP). DESIGN: Cross-sectional questionnaire within the Translational Research in Pelvic Pain clinical cohort study. SETTING: Women with CPP, with subgroups of women with endometriosis (EAP), interstitial cystitis/bladder pain syndrome (BPS), comorbid endometriosis and interstitial cystitis/bladder pain syndrome (EABP), and those with pelvic pain without endometriosis or interstitial cystitis/bladder pain syndrome (PP). POPULATION OR SAMPLE: A total of 100 participants. METHODS: Descriptive and comparative analysis from flares questionnaire. MAIN OUTCOME MEASURES: The prevalence, characteristics and triggers of short, medium and long symptom flares in CPP. RESULTS: We received 100 responses of 104 questionnaires sent. Seventy-six per cent of women with CPP have ever experienced symptom flares of at least one length (short, medium and/or long). Flares are associated with painful and non-painful symptoms. There is large variation for the frequency, duration, symptoms and triggers for flares. Over 60% of participants reported flares as stopping them from doing things they would usually do, >80% reported thinking about symptoms of flares and >80% reported flares being bothersome. CONCLUSIONS: Flares are prevalent and clinically very important in CPP. More research is needed to elucidate the mechanisms and characteristics underlying flares. Clinical practice should include an enquiry into flares with the aim of finding strategies to lessen their burden.

The Benefits and Harms of Pharmacological Treatment for Postradiation Pelvic Pain: A Systematic Review by the European Association of Urology Chronic Pelvic Pain Panel with Recommendations for Clinical Practice.

Context: Radiotherapy of the pelvis is a widely used method for the treatment of malignancies, and local complications including pain following pelvic radiation therapy are acknowledged complications. Objective: The primary objective is to assess the clinical effectiveness and safety of pharmacological therapies on postradiation pelvic pain. Evidence acquisition: A systematic review of the use of different pharmacological treatments in the management of post-radiation pelvic pain was conducted (PROSPERO-ID: CRD42021249026). Comprehensive searches of EMBASE, Medline, and Cochrane library were performed for publications between January 1980 and April 2021. The primary outcomes were improvement in pain and adverse events following treatment. The secondary outcomes included quality of life, bowel function, and urinary function. Evidence synthesis: After screening 1514 abstracts, four randomised controlled trials were identified, enrolling 355 patients with bladder and anorectal subtypes of postradiotherapy chronic pelvic pain (CPP). A narrative synthesis was performed as heterogeneity of included studies precluded a meta-analysis. A single study reported a significant reduction in pain after 6 mo in patients with bladder pain syndrome treated with hyaluronic acid or hyperbaric oxygen. Anorectal pain was reported to be reduced by the application of 4% formalin, but the use of hyperbaric oxygen in postradiotherapy anorectal pain remains controversial. Adverse event reporting was generally poor. Studies looking at medications used routinely in guidelines for neuropathic pain, such as gabapentin, pregabalin, amitriptyline, and duloxetine, were absent or of poor quality when it came to postradiation pelvic pain. Conclusions: Beneficial effects of hyperbaric oxygen or formalin on pain, quality of life, and functional symptoms were seen in patients with certain CPP subtypes, but the current evidence level is too weak to allow recommendations about the use of any pharmacological treatment for postradiation pelvic pain. Patient summary: Different pharmacological treatments are used to treat pain after radiotherapy, but current studies are of insufficient quality to determine whether these should be recommended and many chronic pelvic pain subtypes are not covered. Further research is needed.

Clinical profiling of specific diagnostic subgroups of women with chronic pelvic pain.

Introduction: Chronic pelvic pain (CPP) is a common condition affecting up to 26.6% of women, with many suffering for several years before diagnosis and/or treatment. Its clinical presentation is varied and there are frequently comorbid conditions both within and outside the pelvis. We aim to explore whether specific subgroups of women with CPP report different clinical symptoms and differing impact of pain on their quality of life (QoL). Methods: The study is part of the Translational Research in Pelvic Pain (TRiPP) project which is a cross-sectional observational cohort study. The study includes 769 female participants of reproductive age who completed an extensive set of questions derived from standardised WERF EPHect questionnaires. Within this population we defined a control group (reporting no pelvic pain, no bladder pain syndrome, and no endometriosis diagnosis, N = 230) and four pain groups: endometriosis-associated pain (EAP, N = 237), interstitial cystitis/bladder pain syndrome (BPS, N = 72), comorbid endometriosis-associated pain and BPS (EABP, N = 120), and pelvic pain only (PP, N = 127). Results: Clinical profiles of women with CPP (13-50 years old) show variability of clinical symptoms. The EAP and EABP groups scored higher than the PP group (p < 0.001) on the pain intensity scales for non-cyclical pelvic pain and higher than both the BPS and PP groups (p < 0.001) on the dysmenorrhoea scale. The EABP group also had significantly higher scores for dyspareunia (p < 0.001), even though more than 50% of sexually active participants in each pain group reported interrupting and/or avoiding sexual intercourse due to pain in the last 12 months. Scores for the QoL questionnaire (SF-36) reveal that CPP patients had significantly lower QoL across all SF-36 subscales (p < 0.001). Significant effects were also observed between the pain groups for pain interference with their work (p < 0.001) and daily lives (p < 0.001), with the EABP suffering more compared to the EAP and PP groups (p < 0.001). Discussion: Our results demonstrate the negative impact that chronic pain has on CPP patients' QoL and reveal an increased negative impact of pain on the comorbid EABP group. Furthermore, it demonstrates the importance of dyspareunia in women with CPP. Overall, our results demonstrate the need for further exploration of interventions targeting QoL more broadly and suggest that novel approaches to classifying women with CPP are needed.

Comprehensive quantitative sensory testing shows altered sensory function in women with chronic pelvic pain: results from the Translational Research in Pelvic Pain (TRiPP) Study.

ABSTRACT: Chronic pelvic pain (CPP), despite its high prevalence, is still relatively poorly understood mechanistically. This study, as part of the Translational Research in Pelvic Pain (TRiPP) project, has used a full quantitative sensory testing (QST) paradigm to profile n = 85 women with and without CPP (endometriosis or bladder pain specifically). We used the foot as a control site and abdomen as the test site. Across 5 diagnostically determined subgroups, we found features which are common across different aetiologies, eg, gain of function in pressure pain threshold (PPT) when assessing responses from the lower abdomen or pelvis (referred pain site). However, disease-specific phenotypes were also identified, eg, greater mechanical allodynia in endometriosis, despite there being large heterogeneities within diagnostic groups. The most common QST sensory phenotype was mechanical hyperalgesia (>50% across all the groups). A "healthy' sensory phenotype was seen in <7% of CPP participants. Specific QST measures correlated with sensory symptoms assessed by the painDETECT questionnaire (pressure-evoked pain [painDETECT] and PPT [QST] [ r = 0.47, P < 0.001]; mechanical hyperalgesia (painDETECT) and mechanical pain sensitivity [MPS from QST] [ r = 0.38, P = 0.009]). The data suggest that participants with CPP are sensitive to both deep tissue and cutaneous inputs, suggesting that central mechanisms may be important in this cohort. We also see phenotypes such as thermal hyperalgesia, which may be the result of peripheral mechanisms, such as irritable nociceptors. This highlights the importance of stratifying patients into clinically meaningful phenotypes, which may have implications for the development of better therapeutic strategies for CPP.

The Unmet Needs for Studying Chronic Pelvic/Visceral Pain Using Animal Models.

The different definitions of chronic pelvic/visceral pain used by international societies have changed over the years. These differences have a great impact on the way researchers study chronic pelvic/visceral pain. Recently, the role of systemic changes, including the role of the central nervous system, in the perpetuation and chronification of pelvic/visceral pain has gained weight. Consequently, researchers are using animal models that resemble those systemic changes rather than using models that are organ- or tissue-specific. In this review, we discuss the advantages and disadvantages of using bladder-centric and systemic models, enumerating some of the central nervous system changes and pain-related behaviors occurring in each model. We also present some drawbacks when using animal models and pain-related behavior tests and raise questions about possible, yet to be demonstrated, investigator-related bias. We also suggest new approaches to study chronic pelvic/visceral pain by refining existing animal models or using new ones.

Myofascial Pelvic Pain: Best Orientation and Clinical Practice. Position of the European Association of Urology Guidelines Panel on Chronic Pelvic Pain.

CONTEXT: Despite the high prevalence of a myofascial pain component in chronic pelvic pain (CPP) syndromes, awareness and management of this component are lacking among health care providers. OBJECTIVE: To summarize the current state of the art for the management of myofascial pain in chronic primary pelvic pain syndromes (CPPPS) according to scientific research and input from experts from the European Association of Urology (EAU) guidelines panel on CPP. EVIDENCE ACQUISITION: A narrative review was undertaken using three sources: (1) information in the EAU guidelines on CPP; (2) information retrieved from the literature on research published in the past 3 yr on myofascial pelvic pain; and (3) expert opinion from panel members. EVIDENCE SYNTHESIS: Studies confirm a high prevalence of a myofascial pain component in CPPPS. Examination of the pelvic floor muscles should follow published recommendations to standardize findings and disseminate the procedure. Treatment of pelvic floor muscle dysfunction and pain in the context of CPP was found to contribute to CPP control and is feasible via different physiotherapy techniques. A multidisciplinary approach is the most effective. CONCLUSIONS: Despite its high prevalence, the myofascial component of CPP has been underevaluated and undertreated to date. Myofascial pain must be assessed in all patients with CPPPS. Treatment of the myofascial pain component is relevant for global treatment success. Further studies are imperative to reinforce and better define the role of each physiotherapy technique in CPPPS. PATIENT SUMMARY: Pain and inflammation of the body's muscle and soft tissues (myofascial pain) frequently occurs in pelvic pain syndromes. Its presence must be evaluated to optimize management for each patient. If diagnosed, myofascial pain should be treated.

Quality-of-life reporting in randomized controlled trials shaping the EAU Renal Cell Carcinoma Guidelines.

INTRODUCTION: Quality-of-life (QoL) metrics' importance in patient care has been increasingly recognized and has led oncological societies to issue clinical guidances on their collection. We aim to describe how current RCTs shaping the EAU RCC Guidelines collect QoL metrics and how long they report them. MATERIALS AND METHODS: We searched EAU Renal Cell Carcinoma Guidelines' references for phase 3 clinical trials. Data related to if, for how long and how QoL metrics were collected and/or reported were obtained. RESULTS: Over 35 identified trials, with 16 (46 %) having complete information, being included on our study. Among the analyzed studies, 11 (69 %) were on metastasized/advanced disease setting and 5 (31 %) in adjuvant therapy after surgery; none included QoL as a primary outcome, and 13 (81 %) reported positive QoL results. Regarding timings, all (100 %) studies reported QoL during intervention, and at end of treatment, 9 (56 %) until progression and none (0 %) until death. Median OS was reached in 11 (69 %) studies. Across all studies, the median QoL reporting time was of 7.6 (5.0-12.0) months and the median observation time of 27.1 (22.5-53.1) months. As such, trials reported QoL metrics for a of 28.0 % of the possible time at time of their publications. CONCLUSIONS: We found that only 46 % of RCTs reported on QoL metrics and most of these evaluated QoL during an insufficient timeframe. Most studies in this field are not adequately informing on QoL metrics, even when they are reported.

Review of 175 Cases of Tuberculosis Infections Affecting the Urogenital System.

OBJECTIVE: Urogenital tuberculosis and disseminated tuberculosis affecting urogenital system are more fre quent in developing countries but are often overlooked in developed ones. We aimed to compare clinical characteristics and outcomes of urogenital tuberculosis and disseminated tuberculosis affecting the urogeni tal system. MATERIAL AND METHODS: We retrospectively reviewed data from patients with tuberculosis in the urogenital system, diagnosed in a tertiary center in a European country, from 2008 to 2018. Cases were divided into urogenital tuberculosis and disseminated tuberculosis affecting the urogenital system and compared. RESULTS: We included 172 patients, 31 with urogenital tuberculosis and 141 with disseminated tuberculosis affecting urogenital system. Patients with disseminated tuberculosis affecting the urogenital system were younger (median 45 vs. 64 years, P=.001), more likely to be male (80 vs. 55%, P=.005), or having risk fac tors for the disease (84 vs. 23%, P=.005) than patients with urogenital tuberculosis. Patients with urogenital tuberculosis presented most commonly with symptoms related to the urinary tract, with 52% complaining of lower urinary tract symptoms attributed to urinary tract infections and 48% of dysuria, while patients with disseminated tuberculosis affecting the urogenital system presented mainly with systemic symptoms, with 89% complaining of malaise, 62% of fever, and 57% of anorexia. Patients with urogenital tuberculosis were more likely to need urological surgery as part of their treatment (71 vs. 5%, P < .001) and patients with dis seminated tuberculosis affecting the urogenital system were more likely to die due to tuberculosis (10 vs. 21%, P < .001). CONCLUSION: Tuberculosis of the urogenital system can have multiple clinical presentations, and a simple diagnostic algorithm does not exist. In the presence of urogenital tuberculosis in injected drug users, immu nosuppressed individuals, or patients with systemic symptoms, we should think of disseminated tuberculosis affecting the urogenital system and remember these patients less frequently need surgery but entail a worst outcome.

Effect of Intratrigonal Botulinum Toxin in Patients with Bladder Pain Syndrome/Interstitial Cystitis: A Long-Term, Single-Center Study in Real-Life Conditions.

The high percentage of treatment failures seen in patients with bladder pain syndrome/interstitial cystitis (BPS/IC) managed conservatively frequently demands invasive treatment options. We aimed to evaluate the long-term efficacy and adverse events of intratrigonal botulinum toxin injection in such circumstances, as well as to determine possible predictors of response to toxin treatment. A retrospective cohort study included 47 female BPS/IC patients treated with onabotulinum toxin A (OnabotA) in a tertiary hospital between the years 2009 and 2022. All patients received 100 U of OnabotA in ten injections limited to the trigonal area. Patients were divided into three groups based on their treatment response as responders, non-responders and lost to follow-up due to non-medical reasons. The clinical and surgical records of the individuals were retrieved, including the 10-point visual analogue scale (VAS), the number of treatments, the time between injections, and the age at the first injection. A total of 25 patients (>50% of the cohort) were long-term responders, but none of the evaluated parameters was a predictor for this circumstance: age, pain intensity, or duration of improvement following the injection. The time between injections was stable (around 1 year). No severe adverse events were registered. The intratrigonal injection of botulinum toxin in patients with BPS/IC was an effective and safe long-term treatment for patients' refractory to conservative forms of treatment. Age, basal pain intensity, and time to injection request did not predict long-term response to OnaBotA.

The value of surgeon's perception during transurethral resection of bladder tumors: can we trust in our eyes and experience to predict grade and staging?

Transurethral resection of newly diagnosed bladder tumors (TURBT) is a hallmark ¡n the treatment of bladder cancer. We evaluated the surgeon capacity to predict bladder tumor stage (T), grade, and presence of muscular layer based upon cystoscopic characteristics during primary TURBT. Methods: Prospective study enrolling 100 consecutive patients undergoing primary TURBT for newly diagnosed bladder cancers. Cystoscop¡c tumor characteristics at the time of TURBT was evaluated by an urology senior and a resident regarding histological grade, invasion (T stage), and presence of muscular layer in the specimen. We analyzed the surgeon's accuracy in predicting these parameters using the final histology as gold standard. In addition, the predictive capacity between seniors and residents was compared. Results: The resident's arm correctly predicted tumor invasiveness in 76% of cases, while seniors correctly predicted 87% of cases. Regarding tumor grade, high grade cancer was reported in 78% of the specimens and 75% and 77% of them were correctly predicted by residents and seniors, respectively. Finally, 80% of the TURBT specimens had muscle representativeness. In nearly 75% of the cases, both resident and senior correctly predicted the TURBT resection depth (presence of detrusor muscle in the specimen). The positive predictive value for this parameter was 79% for the resident, and 81% for the senior, and the negative predictive value was 25% and 40%, respectively. Conclusion: The surgeon's naked eye analysis showed a good, but limited predictive ability to detect non-muscle invasive and high-grade bladder tumors in TURBT specimens. Positive predictive value for muscle representativeness is around 80%, which reinforces the need of carrying out a careful and extensive TURBT, irrespective of the surgeon experience.

Silodosin Improves Pain and Urinary Frequency in Bladder Pain Syndrome/Interstitial Cystitis Patients.

Purpose: Bladder Pain Syndrome/Interstitial Cystitis (BPS/IC) is a bladder-related chronic inflammatory disease. Data indicate that stress enhances the excitability of bladder nociceptors through the stimulation of alpha1A-adrenoceptors. Stress is known to play a crucial role in BPS/IC patients. We aimed to assess the efficacy and safety of daily silodosin in refractory BPS/IC female patients and its correlation with stress coping. Materials and Methods: An open-label trial was conducted with 20 refractory BPS/IC patients. Evaluations occurred at baseline and the 8th and 12th weeks. Primary endpoint was bladder pain evaluated by visual analogue scale (VAS). Secondary endpoints included daily frequency, nocturia and maximum voided volume obtained from a 3-day bladder diary, the O'Leary−Sant Symptom Score, and two questions accessing stress coping. Patients initiated daily doses of 8 mg silodosin, which could be titrated to 16 mg. Median values with percentiles 25 and 75 (25; 75) were used. Wilcoxon signed-rank test was used for comparisons. A minimally important difference of 3 points for pain was established to define clinically relevant improvement. Results: Median age was 56 years. Median pain score decreased from 8.00 (6.00; 8.00) at baseline to 4.00 (2.00; 5.50) (p < 0.001), meaning that the primary endpoint was reached. Total urinary frequency decreased from 14.00 (13.00; 21.00) to 9.00 (7.50; 11.00) (p < 0.05), and all the other secondary endpoints also showed a statistically significant improvement. Eleven patients improved by ≥3 pain points in VAS, meaning that 65% of patients that ended the study protocol achieved clinical significant improvement or, in the full analysis set, that 55% of the 20 initial patients improved significantly. Fourteen (82%) decreased by ≥2 micturitions/day. Overall, the cohort's stress coping was low. Conclusions: Silodosin can be an effective and well-tolerated treatment for refractory BPS/IC female patients.

Analysis of benign prostatic obstruction surgery: A long-term evaluation in a real-life context.

OBJECTIVE: Surgery is the treatment for male lower urinary tract symptoms (LUTS) relat-ed to benign prostatic obstruction (BPO) refractory to pharma-cological treatment or with complications. This study aimed to assess factors associated with the need for surgical reinterven-tion and/or continuation of pharmacological treatment. MATERIALS AND METHODS: A retrospective analysis of patients who underwent prostatic surgery for male LUTS associated with BPO between 1 May 2015 and 1 May 2016, with a minimum follow-up of five years, in an academic tertiary hospital.  The type of surgery, preoperative, postoperative and follow-up analysis were collected in a database. RESULTS: A total of 212 patients were included with a mean age of 70 ± 8.66 years at five years follow-up. At 5 years, a total of 86.9% of patients do not need pharmacological treatment and 12% required surgical reintervention. Of the preoperative parameters, it was found a relationship between prior prostatitis and the need for second surgery with an odds ratio of 4.6. CONCLUSIONS: Patients should be informed of the potential need for pharmacological treatment following surgery, or even of the need for reintervention. History of prostatitis seems to be a risk factor for reintervention.

The Role of Urinary VEGF in Observational Studies of BPS/IC Patients: A Systematic Review.

BACKGROUND: Bladder pain syndrome/interstitial cystitis (BPS/IC) is a chronic pain condition, often underdiagnosed, with an important impact on patient quality of life. More recently, an association between VEGF and its receptors has been suggested in BPS/IC pathophysiology, due to their role in promoting angiogenesis and inflammation, which can enhance bladder pain. Eventually, VEGF may be used as a biomarker for the diagnosis and prognostication of BPS/IC. To further clarify this issue, this review aims to critically summarize the available information, giving rise to a solid starting point for future studies. METHODS: We systematically searched PubMed and Embase, using the queries "urinary VEGF", "urinary VEGF" AND "pain", "urinary VEGF" AND "lower urinary tract symptoms" and "urinary VEGF" AND "LUTS" from January 2016 to February 2022. RESULTS: A total of 1026 papers were identified from which 7 articles were included in this study, which assessed 1036 participants. Regarding VEGF levels, overactive bladder (OAB) and healthy patients were used for comparison with BPS/IC patients. VEGF concentration seems to be higher when compared to healthy patients and overactive bladder (OAB) patients. Higher levels of VEGF were associated with pain severity, while a decrease in VEGF concentration was associated with pain and symptom improvement in women. However, these findings were not constant in all studies. CONCLUSIONS: There is a trend toward a relevant association between increased VEGF levels and pain or symptom severity in BPS/IC patients. Although there are some discrepancies among the studies and the number of patients included is small, VEGF and its receptors should be considered for future studies regarding its use in BPS/IC pathophysiology, diagnosis and prognostication.

Management of chronic primary pelvic pain syndromes.

Management of chronic pelvic pain (CPP) remains a huge challenge for care providers and a major burden for healthcare systems. Treating chronic pain that has no obvious cause warrants an understanding of the difficulties in managing these conditions. Chronic pain has recently been accepted as a disease in its own right by the World Health Organization, with chronic pain without obvious cause being classified as chronic primary pain. Despite innumerable treatments that have been proposed and tried to date for CPP, unimodal therapeutic options are mostly unsuccessful, especially in unselected individuals. In contrast, individualised multimodal management of CPP seems the most promising approach and may lead to an acceptable situation for a large proportion of patients. In the present review, the interdisciplinary and interprofessional European Association of Urology Chronic Pelvic Pain Guideline Group gives a contemporary overview of the most important concepts to successfully diagnose and treat this challenging disease.

Treatment of idiopathic overactive bladder with botulinum toxin: real-life results and patients' expectations.

Background: Overactive bladder (OAB) is a prevalent syndrome affecting 11% to 16% of the adult population. When first-line pharmacological therapy is not effective, intradetrusorial injections of onabotulinumtoxinA (BTX-A) might have an important role in controlling symptoms. The main aim of this study was to access both the efficacy and safety of intradetrusor injections of 100U BTX-A in real clinical practice, among women with idiopathic OAB (iOAB). Methods: Retrospective study, based on clinical diaries in 136 iOAB female patients, with or without urinary incontinence, submitted to BTX-A injections, between 2005 and 2018 in a tertiary university hospital. Positive response was considered only when the patient mentioned she had great improvement after the injection, otherwise, it was considered negative. Results: A positive response was obtained in 90 patients (66%) after the first injection. Women with a positive response after the first treatment had 7.5 times more chances to improve with the second (P = .01). Discontinuation of the therapy after the first injection was neither dependent on the presence of incontinence at baseline (P = .73) nor it was related to age (P = .6). On univariate analyses, none of the parameters evaluated was useful of predicting successful response, although there was a trend in women who had had a previous midurethral sling surgery for stress urinary incontinence, to have a lower chance of having a positive response after the first injection (P = .06).Thirty-nine women (29%) had at least 1 adverse event, urinary tract infection, and straining to void were the most frequent. Women above 65 years old had less risk of developing a urinary tract infection (P = .04). Conclusion: In real clinical practice, BTX-A injection is an effective (66%) and safe treatment, capable of improving quality of life. Moreover, responding to the first injection seems to predict good clinical outcomes in the second treatment. This procedure can be done with minimal restrictions.

Treatment of Non-neurogenic Lower Urinary Tract Symptoms-A Review of Key Publications from 2018 Onward.

CONTEXT: A considerable number of studies addressing the management of lower urinary tract symptoms (LUTS) have been published since 2018. OBJECTIVE: To review the key studies involving pharmacological and neuromodulation treatment of LUTS published from 2018 onward. EVIDENCE ACQUISITION: We followed the Preferred Reporting Items for Systematic Review and Meta-analyses (PRISMA) statement. We conducted an Embase/PubMed search of English literature with the words "OAB" or "LUTS" matched with several different treatment modalities. The search ranged between January 2018 and January 2020. All retrieved papers were first reviewed by title and abstract, yielding a total of 236 papers. Additional manuscripts, such as those presented at major meetings, were also included. After revision, 46 publications were included. EVIDENCE SYNTHESIS: Papers on ß3-adrenoreceptor agonists were most abundant. The efficacy and safety of mirabegron in monotherapy and combination therapy were further confirmed by large observational studies and randomized control trials, including one carried out in elderly patients. The use of vibegron for overactive bladder (OAB) was effective and safe in pivotal clinical trials. More database analyses confirm the risk of dementia associated with long-term use of anticholinergics. Onabotulinum toxinA (OnabotA) and sacral neuromodulation provided similar improvement for incontinence in OAB patients at a 2-yr follow-up. Retrospective studies show that OnabotA is effective in men with OAB. New subcutaneous or transcutaneous devices for tibial nerve stimulation were investigated. The potential role of gene therapy in LUTS was assessed in a pilot study. CONCLUSIONS: Important progresses occurred in the pharmacological and neuromodulation treatments of LUTS, which may change clinical practice. Inoculation of gene vectors was investigated for the first time. PATIENT SUMMARY: The investigation in the therapeutic field of lower urinary tract symptoms is active. The search for the best option for each patient continues. This systematic review summarizes the findings of the most recent and relevant studies in the field.

Pharmacology of the lower urinary tract: update on LUTS treatment.

The number of compounds used in the pharmacological treatment of lower urinary tract symptoms (LUTS) of patients who do not respond to conservative measures has been relatively stable during the last decade, with the exception of the introduction of the new class of ß3 adrenoceptor agonists. However, different combinations have been investigated, and the long-term use of these compounds has raised new concerns about adherence and safety. This review summarizes the current state of pharmacology for LUTS, and presents a thorough discussion of the possible challenges concerning their future use. In this narrative review, we analyze the most recent articles related to LUTS pharmacotherapy, after an initial review of mechanisms of bladder function relevant in present clinical practice. The main problems with pharmacotherapy in LUTS are associated with its moderate efficacy, low persistence on treatment, and the incidence of short- and long-term adverse events (AE) associated with some compounds. The long-term AE, such as cognitive impairment in the elderly vulnerable patients associated with antimuscarinic drugs or persistent erectile dysfunction in sexually active men after treatment with 5-α-reductase inhibitors (5-ARI), are some of the problems addressed in this review. Combination therapy taking advantage of the synergistic mechanisms of action between some classes of compounds may overcome AE associated with dose escalation. LUTS pharmacotherapy offers moderate results to most patients but not a full cure. The use of combination drugs to achieve better clinical results, reduce AE and improve both efficacy and adherence, will be used more frequently in the future. The recently raised concern on potential long-term irreversible AE associated with some of these drugs, like antimuscarinics and 5-ARI, are critically important and require further investigation.