Variability in methodology of erectile dysfunction regenerative therapy trials on ClinicalTrials.gov.

OBJECTIVES: To evaluate the variability in the criteria of erectile dysfunction (ED) regenerative therapy trials registered on ClinicalTrials.gov. METHODS: Interventional trials on ClinicalTrials.gov with the keywords "erectile dysfunction" and variations of "shockwave," "platelet rich plasma," "stem cell," "regenerative," and "restorative" were examined. Inclusion/exclusion criteria and primary/secondary outcomes were compared between extracorporeal shockwave therapy (ESWT), platelet rich plasma and stem cell injections (PRP/SC), and other regenerative therapies (ORT) groups. RESULTS: Of the 92 trials analyzed, International Index of Erectile Function (IIEF) score was the most common primary outcome (72%), with a higher prevalence in ESWT trials than PRP/SC or ORT trials (89% vs 44% and 58%, p<.001). Safety/tolerability was a primary outcome for 44% of PRP/SC trials and 25% of ORT trials but no ESWT trials (p<.001). ESWT trials more frequently had sexual/romantic relationship-based inclusion criteria and cancer treatment-related exclusion criteria than PRP/SC and ORT trials. CONCLUSIONS: There is substantial variability in the inclusion/exclusion criteria and outcome measures among ED regenerative therapy trials. ESWT trials most frequently utilized IIEF and had the strictest inclusion/exclusion criteria, suggesting more rigorous and functional outcome-based studies. Conversely, PRP/SC and ORT trials, but not ESWT trials, had safety/tolerability as a primary outcome, likely due to the experimental nature of these therapies. The variability in inclusion/exclusion criteria and outcome measures limits comparison of the various ED regenerative therapies.

Short-term revision rate of Rigicon Testi10TM testicular prosthesis in adolescents and adults: a retrospective chart review.

Testicular prosthesis implantation is a valuable solution for the physical, cosmetic, and psychological challenges associated with testicular loss which may affect males of any age. We evaluated the safety and reliability of the new Rigicon Testi10TM testicular prosthesis in adults and adolescents by performing an IRB-approved retrospective study of data drawn from Patient Information Forms (PIFs). A total of 427 patients (382 adults and 45 adolescents) had at least one testicular prosthesis implanted. Only one adult patient required revision surgery due to rupture of the Rigicon Testi10 TM saline-filled prosthesis. A 40-year-old patient was found to have a leaking prosthesis approximately one week postoperatively, which was suspected to be due to inadvertently punctured by the surgeon during the sterile saline filling process. There were no post-implantation revisions required for adolescent patients. According to our results, Kaplan-Meier calculation of survival from removal or revision was 99.8% for all patients at 54 months (99.7% for adults and 100% for adolescents). The complication rates among patients in this study are lower than those reported in previous published studies. Our study underscores the generally safe nature of testicular prosthesis implantation, as well as the very rare incidence of revision surgery for this new device.

Penoscrotal inflatable penile prosthesis recipients often fully recover from pain at two weeks following placement.

The symptoms and duration of pain following inflatable penile prosthesis (IPP) surgery remains poorly understood. We characterize postoperative pain following penoscrotal 3-piece inflatable penile prosthesis placement in patients managed with a standardized pain management protocol. This is a single-center prospective analysis of 96 virginal penoscrotal 3-piece IPP recipients (9/2019 to 9/2021) excluding patients with chronic pain, IPPs performed with alternative approaches or concomitantly with other surgeries and those with infections. Standardized pain questionnaire was performed by phone on post-operative day (POD) 2, 7, 14, and 30. The primary outcome was self-reported pain scores, measured by pain score 0-10 (0 = no pain, 10 = unbearable, "worst pain you have ever felt") at various locations (incision, penile, scrotal, abdominal) over the first 30 days postoperatively. A majority of pain reported was outside the scrotal area with 67.6% of complaints in the shaft, glans, abdomen and incision. From POD2 to POD30, there was a significant decrease in severe pain from 46.2 to 11.1% (p = 0.05) with an increase in mild pain from 23.1 to 62.4% (p = 0.05). Roughly half of the participants (47.9%, n = 46) reported no pain by POD14. Penoscrotal IPP recipients often fully recover from pain at the two-week period following surgery and those with lingering discomfort predominantly complain of penile shaft and glans pain.

Does climate impact inflatable penile prosthesis infection (IPP) risk? Assessment of temperature and dew point on IPP infections.

BACKGROUND: Variations in climate have been associated with a greater risk of surgical site infections, urinary tract infections, and changes in the skin microbiome; however, limited data exist on the impact of climate on inflatable penile prosthesis (IPP) infections. AIM: We sought to evaluate the impact of climate on the risk of IPP infections in a large international, multicenter cohort. METHODS: We performed a multi-institutional, retrospective study of patients undergoing IPP surgery. We then evaluated whether the month or season, during which surgery was performed, affected device infections. Implant infections were defined as infections requiring device explantation. A univariate logistic regression analysis was undertaken. OUTCOMES: Our primary outcome was implant infection. RESULTS: A total of 5289 patients with a mean age of 62.2 ± 10.8 years received IPP placement. There was a fairly even distribution of implants performed in each season. A total of 103 (1.9%) infections were recorded. There were 32 (31.1%) IPP infections in patients who underwent surgery in the summer, followed by 28 (27.2%) in the winter, 26 (25.2%) in the spring, and 17 (16.5%) in the fall. No statistically significant differences were recorded in terms of season (P = .19) and month (P = .29). The mean daily temperature (P = .43), dew point (P = .43), and humidity (P = .92) at the time of IPP placement was not associated with infection. CLINICAL IMPLICATIONS: These findings provide reassurance to prosthetic urologists that infection reduction strategies do not need to be tailored to local climate. STRENGTHS AND LIMITATIONS: Climate data were not directly recorded for each hospital, but rather based on the monthly averages in the city where the surgery was performed. CONCLUSION: The climate at time of IPP placement and time of year of surgery is not associated with IPP infection risk.

5qSMA: standardised retrospective natural history assessment in 268 patients with four copies of SMN2.

Newborn screening for 5qSMA offers the potential for early, ideally pre-symptomatic, therapeutic intervention. However, limited data exist on the outcomes of individuals with 4 copies of SMN2, and there is no consensus within the SMA treatment community regarding early treatment initiation in this subgroup. To provide evidence-based insights into disease progression, we performed a retrospective analysis of 268 patients with 4 copies of SMN2 from the SMArtCARE registry in Germany, Austria and Switzerland. Inclusion criteria required comprehensive baseline data and diagnosis outside of newborn screening. Only data prior to initiation of disease-modifying treatment were included. The median age at disease onset was 3.0 years, with a mean of 6.4 years. Significantly, 55% of patients experienced symptoms before the age of 36 months. 3% never learned to sit unaided, a further 13% never gained the ability to walk independently and 33% of ambulatory patients lost this ability during the course of the disease. 43% developed scoliosis, 6.3% required non-invasive ventilation and 1.1% required tube feeding. In conclusion, our study, in line with previous observations, highlights the substantial phenotypic heterogeneity in SMA. Importantly, this study provides novel insights: the median age of disease onset in patients with 4 SMN2 copies typically occurs before school age, and in half of the patients even before the age of three years. These findings support a proactive approach, particularly early treatment initiation, in this subset of SMA patients diagnosed pre-symptomatically. However, it is important to recognize that the register will not include asymptomatic individuals.

Long-term efficacy and safety of nusinersen in adults with 5q spinal muscular atrophy: a prospective European multinational observational study.

Background: Evidence for the efficacy of nusinersen in adults with 5q-associated spinal muscular atrophy (SMA) has been demonstrated up to a period of 16 months in relatively large cohorts but whereas patients reach a plateau over time is still to be demonstrated. We investigated the efficacy and safety of nusinersen in adults with SMA over 38 months, the longest time period to date in a large cohort of patients from multiple clinical sites. Methods: Our prospective, observational study included adult patients with SMA from Germany, Switzerland, and Austria (July 2017 to May 2022). All participants had genetically-confirmed, 5q-associated SMA and were treated with nusinersen according to the label. The total Hammersmith Functional Motor Scale Expanded (HFMSE) and Revised Upper Limb Module (RULM) scores, and 6-min walk test (6 MWT; metres), were recorded at baseline and 14, 26, and 38 months after treatment initiation, and pre and post values were compared. Adverse events were also recorded. Findings: Overall, 389 patients were screened for eligibility and 237 were included. There were significant increases in all outcome measures compared with baseline, including mean HFMSE scores at 14 months (mean difference 1.72 [95% CI 1.19-2.25]), 26 months (1.20 [95% CI 0.48-1.91]), and 38 months (1.52 [95% CI 0.74-2.30]); mean RULM scores at 14 months (mean difference 0.75 [95% CI 0.43-1.07]), 26 months (mean difference 0.65 [95% CI 0.27-1.03]), and 38 months (mean difference 0.72 [95% CI 0.25-1.18]), and 6 MWT at 14 months (mean difference 30.86 m [95% CI 18.34-43.38]), 26 months (mean difference 29.26 m [95% CI 14.87-43.65]), and 38 months (mean difference 32.20 m [95% CI 10.32-54.09]). No new safety signals were identified. Interpretation: Our prospective, observational, long-term (38 months) data provides further real-world evidence for the continuous efficacy and safety of nusinersen in a large proportion of adult patients with SMA. Funding: Financial support for the registry from Biogen, Novartis and Roche.

[Certification by the German Society for Neurorehabiliation, DGNR : Performance and quality of the "Centers for weaning from a ventilator in early neurological and neurosurgical rehabilitation"]. / Zertifizierung der Deutschen Gesellschaft für Neurorehabilitation e. V., DGNR : Leistung und Qualität der "Zentren für Beatmungsentwöhnung in der neurologisch-neurochirurgischen Frührehabilitation".

BACKGROUND: Certification of centers for weaning from a ventilator in neurological neurosurgical early rehabilitation (NNER) by the German Society for Neurorehabilitation (DGNR) is possible since 1 October 2021. OBJECTIVE: The results of certification of facilities in the first year after starting the procedure are presented. MATERIAL AND METHODS: As part of the certification process 28 criteria are assessed including a set of mandatory characteristics of the facility. The criteria are divided into structural criteria (i = 7), diagnostic criteria (i = 6), personnel criteria (i = 3), internal organization criteria (i = 7), and quality management criteria (i = 5). RESULTS: A total of 13 centers were certified in the first year, with a combined total of 283 beds for weaning from a ventilator in the NNER and served 2278 persons to be weaned from a ventilator in the year before certification, with a median of 134 per facility (range 44-414). Only rarely was weaning unsuccessful, requiring conversion to home mechanical ventilation before discharge (invasive home mechanical ventilation median per facility 10 persons, range 2-25; non-invasive home mechanical ventilation median 0 persons, range 0-57). A high level of process and structural quality was documented for the certified centers: across all areas of assessment, the individual certification criteria were met in the vast majority of cases (median degree of complete fulfilment 86%) or met with improvement potentials documented by the auditors (median 11%). CONCLUSION: Successful weaning in NNER and a high level of process and structural quality can be demonstrated by the certification results of centers that follow this integrative approach to weaning from a ventilator in a NNER setting.

Isolation of phosphorus-hyperaccumulating microalgae from revolving algal biofilm (RAB) wastewater treatment systems.

Excess phosphorus (P) in wastewater effluent poses a serious threat to aquatic ecosystems and can spur harmful algal blooms. Revolving algal biofilm (RAB) systems are an emerging technology to recover P from wastewater before discharge into aquatic ecosystems. In RAB systems, a community of microalgae take up and store wastewater P as polyphosphate as they grow in a partially submerged revolving biofilm, which may then be harvested and dried for use as fertilizer in lieu of mined phosphate rock. In this work, we isolated and characterized a total of 101 microalgae strains from active RAB systems across the US Midwest, including 82 green algae, 9 diatoms, and 10 cyanobacteria. Strains were identified by microscopy and 16S/18S ribosomal DNA sequencing, cryopreserved, and screened for elevated P content (as polyphosphate). Seven isolated strains possessed at least 50% more polyphosphate by cell dry weight than a microalgae consortium from a RAB system, with the top strain accumulating nearly threefold more polyphosphate. These top P-hyperaccumulating strains include the green alga Chlamydomonas pulvinata TCF-48 g and the diatoms Eolimna minima TCF-3d and Craticula molestiformis TCF-8d, possessing 11.4, 12.7, and 14.0% polyphosphate by cell dry weight, respectively. As a preliminary test of strain application for recovering P, Chlamydomonas pulvinata TCF-48 g was reinoculated into a bench-scale RAB system containing Bold basal medium. The strain successfully recolonized the system and recovered twofold more P from the medium than a microalgae consortium from a RAB system treating municipal wastewater. These isolated P-hyperaccumulating microalgae may have broad applications in resource recovery from various waste streams, including improving P removal from wastewater.

Single Dilation in Primary Inflatable Penile Prosthesis Placement Is Associated With Fewer Corporal Complications Than Sequential Dilation.

OBJECTIVE: To assess the difference in outcomes between single dilation (SingD) and sequential dilation (SeqD) in primary penile implantation, hypothesizing that patients who undergo SeqD had higher rates of noninfectious complications. METHODS: We performed a multicenter, retrospective study of men undergoing primary inflatable penile prosthesis placement. Intraoperative complications and postoperative noninfectious outcomes were assessed between the two groups. Multivariable analysis was performed to identify predictors of complications. RESULTS: A total of 3293 patients met inclusion criteria. After matching, there were 379 patients who underwent SingD and 379 patients who underwent SeqD. There was no significant difference in intraoperative complications between patients who underwent SingD vs SeqD, nor was there any difference in cylinder length (20 cm with interquartile range [IQR] 18-21 cm vs 20 cm with IQR 18-20 cm respectively, P = .4). On multivariable analysis, SeqD (OR 5.23 with IQR 2.74-10, P < .001) and older age (OR 1.04 with IQR 1.01-1.06, P = .007) were predictive of postoperative noninfectious complications. There was no significant difference in intraoperative complications between patients who underwent SingD vs SeqD, nor was there any difference in cylinder length. SeqD and older age were predictive of postoperative noninfectious complications. CONCLUSION: During inflatable penile prosthesis placement in the uncomplicated patient without fibrosis, SingD is a safe technique to utilize during implantation that will minimize postoperative adverse events, and promote device longevity without loss of cylinder length.

Survival From Revision Surgery for New Rigicon Infla10 Three-piece Inflatable Penile Prosthesis Is Comparable to Preceding Devices.

OBJECTIVE: To report the incidence of the reoperation surgeries of nearly all the Rigicon Infla10 implants performed since device introduction in 1/2019. Inflatable penile prosthesis has some of the highest survival from revision surgery of any medical device implanted in humans [1]. We expand on previous Rigicon Infla10 research, adding more patients and increasing follow-up duration [2]. MATERIALS AND METHODS: 535 patients had Rigicon Infla10 devices implanted from 1/2019 to 8/2022. 103 surgeons from 26 centers in 15 countries participated in the study. Patient information forms were analyzed from virtually all implantations. Explantation or revision surgery for mechanical failure, infection, other medical reasons, and patient dissatisfaction were cataloged. SPSS 25.0 (IBM) was used for the statistical analysis of Kaplan Meier survival statistics. RESULTS: Mean follow-up was 24.2months (7-43months). Mean patient age was 56years. Reoperation was necessary for 3.5% of subjects. Revision for mechanical failure occurred in 2.24% (12/535). The rate of explant for patient dissatisfaction was 0.56% (3/535). Revision for component out of place was 0.37% (2/535) with an infection rate and unsuccessful Peyronie's correction being 0.19% (1/535). Survival from requiring another corrective surgery at 1, 2, and 3years was 96.4%, 95.0%, and 94.0%, respectively. These initial survival rates compare favorably to devices currently available, which have been repeatedly enhanced to improve reliability. CONCLUSION: In its first 2-3years of availability, The Rigicon Infla10 inflatable penile prosthesis shows freedom from revision comparable to existing enhanced devices that have been on the market for decades.

Effect of mechanical insufflation-exsufflation for ineffective cough on weaning duration in diseases of the peripheral or central nervous system (MEDINE): study protocol for a randomised controlled trial in a neurological weaning centre.

INTRODUCTION: Patients with neurological or neurosurgical disease can suffer from impaired cough, which may result in life-threatening retention of tracheobronchial secretions, atelectasis, pneumonia and finally death. Due to a lack of alternatives and pathophysiological plausibility, the application of mechanical insufflation-exsufflation (MI-E) has already become international standard care in neuromuscular disease and spinal cord injury although a lack of evidence for efficacy. High-quality studies to support the use of MI-E in neurological and neurosurgical patients during weaning from mechanical ventilation are missing. The goal of this exploratory study is to display the effect size of MI-E intervention on the duration of mechanical ventilation and additional outcomes. METHODS AND ANALYSIS: One hundred adult patients with a cough deficiency or retention of secretion admitted to a neurological intensive care unit (ICU) are planned to be recruited for this randomised controlled trial. Patients are randomised 1:1 to receive either MI-E or best standard care. Observation will take place until discharge from the hospital, death or end of the study period. The primary endpoint of this trial is the duration of mechanical ventilation from randomisation until successful weaning. The outcome will be analysed with Kaplan-Meier estimation and competing risks analyses. Secondary endpoint is the proportion of patients with successful weaning. Further outcomes will include the incidence of hospital-acquired pneumonia, mortality, decannulation rate, length of stay on the ICU and the total score of the Glasgow Coma Scale. ETHICS AND DISSEMINATION: The study was approved by the Medical Ethics Committee of the University of Oldenburg. The findings of this study will be submitted for publication in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: DRKS00020981.

Delayed placement of an inflatable penile prosthesis is associated with a high complication rate in men with a history of ischemic priapism.

BACKGROUND: Corporal fibrosis is known to result from prolonged priapism; however, the impact of the timing of penile prosthesis placement after priapism on complication rates is poorly understood. AIM: We sought to evaluate the impact of timing of inflatable penile prosthesis (IPP) placement on complications in men with a history of ischemic priapism. METHODS: We performed a multicenter, retrospective cohort study of patients with a history of priapism undergoing IPP placement by 10 experienced implantation surgeons. We defined early placement as ≤6 months from priapism to IPP. We identified a 1:1 propensity-matched group of men without a history of priapism and compared complication rates between men who had early placement, late placement, and no history of priapism. OUTCOMES: Our primary outcome was postoperative noninfectious complications, and secondary outcomes included intraoperative complications and postoperative infection. RESULTS: A total of 124 men were included in the study with a mean age of 50.3 ± 12.7 years. A total of 62 had a history of priapism and 62 were matched control subjects. The median duration of priapism was 37 (range, 3-168) hours and the median time from ischemic priapism to IPP placement was 15 months (range, 3 days to 23 years). Fifteen (24%) men underwent early (≤6 months) IPP placement at a median time of 2 months (range, 3 days to 6 months) following the ischemic priapism event. The remaining 47 (76%) underwent placement >6 months following priapism at a median time of 31.5 months (range, 7 months to 23 years). The complication rate in the delayed placement group was 40.5% compared with 0% in the early placement group and control group. Cylinder-related complications such as migration or leak accounted for 8 (57%) of 14 of the postoperative noninfectious complications. Full-sized cylinders were used in all patients who had a cylinder related complication. CLINICAL IMPLICATIONS: Priapism patients should be referred to prosthetic experts early to decrease complication rates in those needing an IPP. STRENGTHS AND LIMITATIONS: This is a multicenter study from experienced prosthetic urologists but is limited by the retrospective nature and small number of patients in the early placement group. CONCLUSION: IPP complication rates are high in men with a history of ischemic priapism, especially when implantation is delayed beyond 6 months.

Defining the incidence and management of postoperative scrotal hematoma after primary and complex three-piece inflatable penile prosthesis surgery.

Scrotal hematoma is a challenging complication of penile prosthesis surgery. We characterize the risk of hematoma formation with implementation of standardized techniques to mitigate hematomas and assess for any associated factors in a large multi-institutional penile implant cohort. This was a retrospective review from February 2018 to December 2020 of all patients who underwent inflatable penile prosthesis implantation at 2 high volume implant centers. Cases were defined as "complex" if they involved revision, salvage with removal/replacement, or were performed with concurrent penile, scrotal or intra-abdominal surgeries. The incidence of scrotal hematoma among primary and complex IPP recipients was measured and modifiable and innate risk factors associated with hematoma formation within the two cohorts were tracked. Of 246 men who underwent penile prosthesis surgery, 194 (78.9%) patients underwent primary implantation and 52 (21.1%) were complex. Although hematoma formers in the complex group had comparable drain outputs to primary patients on postoperative day 0 (66.8cc ± 32.5 vs 48.4 ± 27.7, p = 0.470) and postoperative day 1 (40.3cc ± 20.8vs 21.8 ± 11.3 p = 0.125), hematomas in the complex group had a higher propensity for OR evacuation (p = 0.03). Difference in duration of temporary device inflation between 2 (64, 26%) and 4 weeks (182, 74%) did not contribute to hematoma formation (p = 0.562). The incidence of postoperative hematoma formation in complex cases was 9.6% (5/52) and 3.6% in primary cases (7/194) (HR = 2.61, p = 0.072). Complex IPP surgery performed for revision or with ancillary procedures are more likely to result in clinically significant hematomas that require surgical management, suggesting a need for heightened caution in managing these individuals.

Partner Involvement Reduces Postoperative Care Burden Following Penile Prosthesis Placement.

OBJECTIVE: To determine whether preoperative partner involvement at clinic appointments is associated with deviation from a standardized postoperative care pathway for patients undergoing an inflatable penile prosthesis placement. METHODS: This is a retrospective study of 170 patients undergoing primary inflatable penile prosthesis placement performed by a single surgeon between 2017 and 2020. A standardized postoperative clinical pathway was used, including planned follow-up visits at 2 weeks (for wound check and device deflation) and 6 weeks (for device teaching). Patient characteristics, including demographics, partner involvement, and the number of follow-up visits were obtained from the medical record. Logistic regression modeling was performed to determine whether partner involvement was associated with unanticipated follow-up visits. RESULTS: Partners were involved in preoperative visits for 92 patients (54%). Additional unplanned follow-up visits were observed for 58 patients (34%) between 0 and 6 weeks and for 28 patients (16%) after 6 weeks from surgery. Partner involvement was associated with reduced odds of unanticipated follow-up visits, both between 0 and 6 weeks (odds ratios 0.37, 95% CI 0.18-0.75) and after 6 weeks (odds ratios 0.33, 95% CI 0.13-0.81) in adjusted models. CONCLUSION: Having a patient's partner involved during the preoperative period is associated with a significant reduction in unanticipated follow-up. We would recommend that urologists routinely encourage patients considering the insertion of a penile prosthesis to involve their partners in perioperative visits. Further research needed is needed to determine how to best support patients during surgical decision-making and through the postoperative period.