ColabSeg: An interactive tool for editing, processing, and visualizing membrane segmentations from cryo-ET data.

Cellular cryo-electron tomography (cryo-ET) has emerged as a key method to unravel the spatial and structural complexity of cells in their near-native state at unprecedented molecular resolution. To enable quantitative analysis of the complex shapes and morphologies of lipid membranes, the noisy three-dimensional (3D) volumes must be segmented. Despite recent advances, this task often requires considerable user intervention to curate the resulting segmentations. Here, we present ColabSeg, a Python-based tool for processing, visualizing, editing, and fitting membrane segmentations from cryo-ET data for downstream analysis. ColabSeg makes many well-established algorithms for point-cloud processing easily available to the broad community of structural biologists for applications in cryo-ET through its graphical user interface (GUI). We demonstrate the usefulness of the tool with a range of use cases and biological examples. Finally, for a large Mycoplasma pneumoniae dataset of 50 tomograms, we show how ColabSeg enables high-throughput membrane segmentation, which can be used as valuable training data for fully automated convolutional neural network (CNN)-based segmentation.

Anesthetic Technique (Spinal vs. General Anesthesia) in Holmium Laser Enucleation of the Prostate: Retrospective Analysis of Procedural and Functional Outcomes among 1,159 Patients.

OBJECTIVE: The aim of the study was to compare procedural efficacy, early and late functional outcomes in holmium laser enucleation of the prostate (HoLEP) under spinal anesthesia (SA) versus general anesthesia (GA). METHODS: We retrospectively reviewed patients undergoing HoLEP at our institution between 2012 and 2017. Standard pre-, peri-, and postoperative characteristics were compared according to anesthetic technique. Multivariable logistic regression analyses (MVAs) were employed to study the impact of SA on procedural efficacy and postoperative complications. RESULTS: Our study cohort consisted of 1,159 patients, of whom 374 (32%) underwent HoLEP under SA. While a medical history of any anticoagulation/antiplatelet therapy except low-dose acetylsalicylic acid was significantly more common among patients undergoing GA (16% vs. 10%, p = 0.001), no other significant differences in preoperative characteristics were noted including age, body mass index, American Society of Anesthesiologists Classification (ASA), prostate size, or International Prostate Symptom Score (IPSS), and quality of life scores. Patients under SA exhibited shorter times of enucleation 42 min (interquartile range [IQR]:27-59 vs. 45 min [IQR: 31-68], p = 0.002), and combined time of enucleation/morcellation/coagulation (57 min [IQR: 38-85] vs. 64 min [IQR: 43-93], p = 0.002), as well as fewer complications (Clavien-Dindo ≥3) (12 [3.2%] vs. 55 [7%], p = 0.013). These associations were confirmed in MVA. Patients did not differ significantly with regard to early micturition including post-void residual volume and maximum flow-rate improvement. At a median follow-up of 33 months (IQR: 32-44), patients with SA had a lower IPSS score (median 3 [IQR: 1-6] vs. 4 [IQR: 2-7], p = 0.039). However, no significant differences were observed with respect to any urinary incontinence, urge symptoms, and postoperative pain. CONCLUSION: In this large retrospective series, HoLEP under SA was a safe and efficacious procedure with comparable early and long-term functional outcomes.

Learning benefits of live surgery and semi-live surgery in urology-informing the debate with results from the International Meeting of Reconstructive Urology (IMORU) VIII.

PURPOSE: To analyze the perceived learning opportunities of participants of the International Meeting on Reconstructive Urology (IMORU) VIII for both live surgery demonstrations (LSD) and semi-live surgery demonstrations (SLSD). Safety and educational efficacy of LSD and SLSD at live surgery events (LSE) have been debated extensively, however, objective data comparing learning benefits are missing. METHODS: We conducted a detailed survey, which employed the Kirkpatrick model, a well-established assessment method of training models, to investigate participants preferences as well as the learning benefit of LSE. Furthermore, we employed an audience response system and the Objective Structured Assessment of Technical Skills (OSATS), a well-established assessment method of surgery skills, to let our participants rate the perceived learning opportunity of LSD and SLSD. RESULTS: Of 229 participants at the IMORU VIII, 39.7% returned our questionnaires. 90% stated that they prefer LSD. On all levels of Kirkpatrick's training evaluation model, the IMORU received high ratings, suggesting a high learning benefit. For the assessment of OSATS, a total of 23 surgical cases were evaluable. For all six utilized items, LSD scored significantly better ratings than SLSD. CONCLUSION: Our study suggests that there is still a rationale for LSD, as participants attributed a statistically significant higher learning benefit to LSD over SLDS. Evaluation of the survey showed that for LSE such as the IMORU VIII, a high learning benefit can be expected. Considering that most of our participants are active surgeons with high caseloads, their opinion on the educational value of LSE is of high relevance.

Continence and Complication Rates of Artificial Urinary Sphincter Devices (AMS 800) for Parkinson and Stroke Patients with Incontinence after Prostate Surgery: Retrospective Analysis of a Prospective Database.

OBJECTIVES: The artificial urinary sphincter (AUS) is the gold standard treatment for severe stress urinary incontinence (SUI). According to the literature, patients suffering from Parkinson's disease (PD) or stroke (ST) show adverse continence outcomes after prostate surgery and, therefore, constitute a challenging cohort for continence surgery. However, little is known with respect to the results of AUS surgery in these patients. A retrospective analysis of our institutional, prospectively maintained AUS database aims to address this aspect with a focus on surgical and functional outcomes. METHODS AND PATIENTS: All data of patients with an AUS implantation were prospectively collected in our database since 2009. The AUS was implanted according to a standardized protocol and activated at 6 weeks postoperatively at our institution. Further follow-up (FU) consisted of pad-test, uroflowmetry, residual urine, and radiography as well as a standardized questionnaire including the Incontinence Quality of Life questionnaire (I-Quol) and International Consultation on Incontinence questionnaire (ICIQ-SF) and is scheduled at 6 and 24 months and every 2 years thereafter. Patients received a preoperative urodynamic evaluation (UD). Patients with normal voiding and storage function were considered for AUS implantation. All patients performed a preoperative test for manual dexterity. Patients with a history of ST or PD were grouped and compared to nonneurological patients. Primary/secondary endpoints of the study were complications/continence. RESULTS: 234 patients were available for analysis. The median FU was 24 months (interquartile range 7-36). Twenty-four patients (10%) had a neurological history (PD and ST). Neurological patients showed significantly worse outcomes regarding continence (objective/subjective/social continence; p = 0.04/p = 0.02/p = 0.1). Significant differences concerning explantation rates were not observed (p = 1). Kaplan-Meier analysis showed no significant difference regarding explantation-free survival (log-rank p = 0.53). CONCLUSION: AUS implantation shows significantly worse continence rates for neurological patients, despite the fact that all patients showed normal UD results and sufficient manual dexterity. Although neurological patients showed worse outcomes for continence, AUS implantation seems to be a safe and viable treatment for patients with a history of neurological disease.

A critical outcome analysis of Asopa single-stage dorsal inlay substitution urethroplasty for penile urethral stricture.

PURPOSE: To critically report outcomes from a contemporary series of patients undergoing single-stage Asopa dorsal inlay urethroplasty for penile stricture. METHODS: First, we retrospectively evaluated patients who underwent Asopa urethroplasty for penile stricture between 2009 and 2016 at our department. Clinical and surgical characteristics were compared across treatment groups (proximal penile, mid-penile, distal penile). Recurrence-free survival was plotted using Kaplan-Meier curves. Treatment satisfaction was assessed using a validated outcome measurement tool. Second, a literature review was performed through Medline to summarize the available evidence on Asopa urethroplasty and put our own results into context. RESULTS: Of 125 patients, 38 (30%), 74 (59%), and 13 (10%) had distal penile, mid-penile, and proximal penile stricture, respectively. Patients with distal strictures were younger and graft length was shorter compared to other groups (P ≤ 0.009). The majority of strictures were iatrogenic (38%), followed by hypospadias related (24%), congenital (17%), traumatic (10%), inflammatory (9%), and post-infectious strictures (2.4%). At a median follow-up of 36 months, overall success rate was 70%. In sensitivity analyses, success rates were only marginally improved to 71% after exclusion of hypospadias- and lichen sclerosus-associated strictures. Patients with mid-penile strictures were significantly more satisfied compared to other groups. Overall, 272 patients from 9 studies in the literature review underwent Asopa urethroplasty and success rates ranged from 73 to 100%. CONCLUSIONS: Success rates of Asopa urethroplasty in penile strictures are lower than previously reported. This is most likely due to both complex stricture etiology and surgical history and last resort single-stage surgery in many cases. Pre-operative counseling must consider high recurrence risk and staged urethroplasty should be discussed in selective cases to optimize patient satisfaction.

Tumor characteristics, oncological and functional outcomes after radical prostatectomy in very young men ≤ 45 years of age.

PURPOSE: Age is an important prognostic factor for functional and oncological outcomes after radical prostatectomy (RP). Considering the long life-expectancy of young patients (≤ 45 years), it remains important to examine their outcomes. METHODS: Of 16.049 patients who underwent RP between 01/2006 and 12/2014 at the Martini-Klinik Prostate Cancer Center, 119 (0.7%) were ≤ 45. Known prognosticators were compared according to patient age at RP (categorical as ≤ 45, > 45 and ≤ 65, > 65 years). Kaplan-Meier plots and Cox-regressions analyzed oncological outcomes [biochemical recurrence (BCR)-free survival and metastasis-free survival (MFS)]. Logistic regressions were used for functional outcome. Urinary continence (UC) was defined as the use of 0 or 1 safety pad/day and potency as an IIEF-5 score of ≥ 18. RESULTS: Compared to their older counterparts, patients ≤ 45 years had more favorable tumor characteristics. Of all patients aged ≤ 45 years, 89% underwent bilateral and 9.3% unilateral nerve-sparing procedure. Five year BCR-free survival and MFS were 80.2% and 98.7% for patients ≤ 45 years, 72.8% and 95.0% for patients > 45 and ≤ 65 years and 70.5% and 94.9% for patients > 65 years. For the same groups, 1-year UC-rates were 97.4%, 89.4%, and 84.7% while 1.3%, 8.2%, and 11.6% used 1-2 pads/24 h. At 1-year, 75.6%, 58.6%, and 45.3% of preoperatively potent patients who underwent bilateral nerve-sparing were considered potent. Younger age was an independent predictor of favorable functional outcome also in multivariable analysis. CONCLUSIONS: Patients aged ≤ 45 years had more favorable tumor characteristics and oncological outcomes. Moreover, younger patients should be counseled about the excellent postoperative continence and potency rates.

The impact of surgical sequence on outcome rates of artificial urinary sphincter implantation: comparative effectiveness of primary, secondary and repeat implantation.

PURPOSE: To determine whether salvage artificial urinary sphincter (AUS) implantation after prior incontinence surgery achieves outcomes comparable to primary AUS implantation. METHODS: We retrospectively evaluated data of patients undergoing AUS implantation from 2009 to 2014. Functional outcome was objectified by 1-h stress pad test, uroflowmetry, post-void residual urine measurement, clinical examination, and chart review. Complications were categorized according to Clavien-Dindo classification system. Kaplan-Meier analysis determined explantation-free survival. RESULTS: A total of 235 patients were included of whom 165 (70.2%) underwent primary AUS. In 70 patients, salvage incontinence surgery was performed, with 24 (10.2%) patients undergoing AUS reimplantation after prior AUS surgery (repeat AUS) and 46 (19.6%) patients undergoing AUS surgery after any other type of incontinence surgery (secondary AUS). There were no significant differences in rates of continence among primary AUS and repeat AUS patients. Patients undergoing secondary AUS had significantly better continence rates than primary and repeat AUS patients. Three-year explantation-free survival rates after AUS insertion were 82.3% (primary AUS), 78.6% (repeat AUS) and 81.5% (secondary AUS). There were no differences in complication rates among the groups. CONCLUSION: AUS is a safe option in the treatment of severe incontinence even after prior AUS or any other prior incontinence surgery and can still achieve satisfactory outcomes as salvage treatment.

Single-stage buccal mucosal graft urethroplasty for meatal stenoses and fossa navicularis strictures: a monocentric outcome analysis and literature review on alternative treatment options.

OBJECTIVES: To describe the operative technique and report outcomes from the largest series of patients who underwent single-stage dorsal inlay buccal mucosal graft urethroplasty (BMGU) for isolated meatal stenoses and fossa navicularis strictures. PATIENTS AND METHODS: First, we evaluated patients who underwent single-stage BMGU for distal urethral strictures (meatus and fossa navicularis) between 2009 and 2016 at our department. Clinical and surgical characteristics were prospectively collected in an institutional database. Recurrence was defined as symptomatic need of any instrumentation during follow-up, was retrospectively assessed by patient interview, and recurrence-free survival was plotted using Kaplan-Meier curves. Second, a systematic literature review was performed through Medline to summarize the available evidence on distal urethroplasty using flaps or grafts. RESULTS: Of 32 patients, 16 (50%) presented with a hypospadias-associated stricture, followed by seven (22%), five (16%), and four (13%) patients with iatrogenic, inflammatory, and congenital strictures, respectively. At a median follow-up of 42 months (IQR 23-65), single-stage dorsal inlay BMGU was successful in 22 patients (69%), and estimated recurrence-free survival rates were 79% and 74% at 12 and 24 months, respectively. Overall, 62 patients from five studies in the literature review underwent BMGU for isolated distal strictures and success rates ranged from 56 to 100%. CONCLUSION: Recurrent meatal stenoses and fossa navicularis strictures represent some of the most complex uro-reconstructive challenges. Inlay BMGU proves to be a valid and efficient last-resort single-stage technique. However, higher recurrence risk must be considered and staged urethroplasty should be discussed individually. Prospective randomized controlled trials are needed to prove the superiority of flaps, grafts or staged approaches over each other in this context.

Functional outcomes of artificial urinary sphincter implantation with distal bulbar double cuff in men with and without a history of external beam radiotherapy: an analysis of a prospective database.

OBJECTIVES: To analyse functional outcomes and complication rates of artificial urinary sphincter (AUS) implantation with a distal bulbar double cuff (DC) for the treatment of stress urinary incontinence (SUI) in men with and without a history of external beam radiotherapy (RT). PATIENTS AND METHODS: Data of all patients undergoing AUS implantation with a distal bulbar DC (DC-AUS) were collected prospectively from 2009 to 2015. Indications for DC implantation were based on urethral risk factors in terms of RT and previous proximal bulbar urethral interventions including, endoscopic or open surgery for urethral stricture or SUI. Implantation was carried out to a standardised protocol. Activation of the AUS was performed 6 weeks after implantation. Further follow-up (FU) included pad test, uroflowmetry, post-void residual urine measurements, radiography, and a standardised questionnaire. Continence and complication rates were compared between patients with a history of RT and non-RT patients. Explantation-free survival was estimated using Kaplan-Meier curves and the log-rank test. Firth's penalized Cox-regression analyses were performed to analyse proportional hazard ratios for explantation. RESULTS: In all, 150 men (median age 70 years, interquartile range [IQR] 66-74) after DC-AUS implantation were available for analysis. Overall, 73 men (48.7%) had a history of RT. The median (IQR) FU was 24 (7.25-36) months. Baseline clinical characteristics only differed regarding previous open SUI surgery (P = 0.016). Social and objective continence was achieved in 94.8% and 84.3% of all patients treated by implantation of a DC-AUS, respectively. Between the RT and non-RT patients there were no statistically significant differences in continence rates [social continence: 100% vs 90.2% (P = 0.194); objective continence: 87% vs 82% (P = 0.877)]. For complications rates there were no significant differences between RT and non-RT patients after DC-AUS implantation [infection (P = 0.09), erosion (P = 0.31), mechanical failures (P = 0.14)]. According to Kaplan-Meier analysis explantation rates in patients with a history of RT (26.0%) vs non-RT patients (20.8%), estimated explantation-free survival, and AUS durability, did not differ significantly (log-rank P = 0.219). CONCLUSION: Our data from a large institutional series indicate DC-AUS implantation to be an effective and safe treatment strategy in men with SUI and a history of RT.

Prospective analysis of artificial urinary sphincter AMS 800 implantation after buccal mucosa graft urethroplasty.

OBJECTIVES: To analyze functional outcomes and complication rates of artificial urinary sphincter (AUS) implantation in patients who had undergone buccal mucosa graft urethroplasty (BMGU) beforehand. PATIENTS AND METHODS: This prospectively maintained single-center database comprises data from 236 patients from 2009 to 2015 who underwent AUS implantation. A total of 17 patients after BMGU were available for analysis. Primary endpoints consisted of continence and complication rates. Continence was defined as no use of safety pads, social continence as < 2 pads per day. Stricture recurrence was defined as a decrease in uroflowmetry, a maximum flow rate < 10 ml/s or residual urine volume (> 100 ml). Kaplan-Meier analysis determined explantation-free survival. RESULTS: Median follow-up was 24 months (interquartile range [IQR] 6-31 months). Indication for AUS implantation was severe urinary incontinence with a history of radical prostatectomy (RRP) in 8 (47.1%), trauma in 1 (5.9%) and TUR-P in 8 (47.1%) patients. Pelvic irradiation was reported in 13 (76.5%) cases. The median length of buccal mucosa graft for urethroplasty was 4 cm (3-5 cm). A double cuff was implanted in 14 patients (82.4%), 3 patients received a single cuff. Complete and social continence was achieved in 76.5% and 100% of the patients, respectively. There was no significant difference in complications and explantation-free survival (log-rank, p = 0.191) between patients who had undergone BMGU before AUS compared to patients with no history of BMGU. CONCLUSIONS: According to the prospective follow-up data in a homogenous cohort, AUS implantation seems to be a viable, safe and effective therapeutic strategy for incontinence treatment despite previous BMGU.

Live surgery in reconstructive urology: evaluation of the surgical outcome and educational benefit of the international meeting on reconstructive urology (IMORU).

PURPOSE: The international meeting on reconstructive Urology (IMORU) is a live surgery event (LSE) where expert surgeons perform various reconstructive surgeries. To evaluate patient safety, an extended follow-up of the complications of two subsequent IMORU meetings were gathered. Also, a detailed survey concerning the participant's assessment of the educational benefit was performed. METHODS: All patients that were operated during the IMORU V and VI were included. Primary endpoint was the analysis of complications. Outcome was reviewed 36 months postoperatively via telephone survey and clinical database assessment, registrating any complications. At IMORU VII all participants were able to participate in a survey using a standardized, not-validated questionnaire concerning the learning effect and the quality of the surgeries. RESULTS: 57 operations by 32 different surgeons were reviewed. The total number of any complications (peri- or postoperative) was n = 9 (15.8%) with three major complications. Four (7%) perioperative complications and five (8.8%) postoperative complications were noted. The Charlson score proved to be the only significant recorded predictor of the incidence of any complication (p = 0.019; univariate logistic regression analysis). Participant survey showed that the surgeons, surgical technique, and surgical presentation were perceived as excellent. Improvement of knowledge and of the surgical armamentarium both received positive ratings. CONCLUSIONS: This is to our knowledge the first follow-up of LSE in the field of reconstructive urology. Rate of complications in general was acceptable. The performed survey showed participants value the quality and the educational benefit. Further studies are needed to improve learning possibilities.

The T-plasty as therapy for recurrent bladder neck stenosis: success rate, functional outcome, and patient satisfaction.

PURPOSE: To determine success rate (SR), functional outcome, and patient satisfaction of a modified YV-plasty for reconstruction of the bladder neck in case of recurrent bladder neck stenosis (BNS) after transurethral surgery of the prostate: the T-plasty. PATIENTS AND METHODS: We identified all patients who underwent T-plasty at our center between December 2008 and July 2016. Patients' charts were reviewed. Patients were queried by telephone and by mail at time of follow-up (FU). Primary endpoint was SR. Secondary endpoints were complications, continence, satisfaction, and changes in quality of life measured by validated questionnaires. RESULTS: Thirty patients underwent the T-plasty. Median age at surgery was 69 (IQR 62-73) years. Most patients had BNS due to TUR-P [n = 25 (83.3%)]. No severe blood loss or severe complications occurred perioperatively. Median FU was 45 (IQR 18-64) months. Three patients were lost to FU. Success rate was 100%. Compared to pre-OP Q max, mean Q max post-OP improved significantly [pre-OP 6.79 (SD ± 4.76) ml/s vs post-OP was 24.42 (SD ± 12.61) ml/s; (t(5) = 4.12, p = 0.009)]. Mean post-void residual urine decreased significantly [pre-OP 140.77 (SD ± 105.41) ml vs post-OP 14.5 (SD ± 22.42) ml; (t(9) = -3.86, p = 0.004)]. One patient developed a de-novo-incontinence post-OP. Mean ICIQ-SF Score was 1.2 (SD ± 2.27). 88.5% of patients were pleased or delighted by surgery. 75% of patients claimed their quality of life has been (strongly) improved. CONCLUSIONS: The T-plasty is a valuable option as treatment of recurrent BNS. SR, rates of continence, and high patient satisfaction are very encouraging.

Dissociation of pentameric to monomeric C-reactive protein localizes and aggravates inflammation: in vivo proof of a powerful proinflammatory mechanism and a new anti-inflammatory strategy.

BACKGROUND: The relevance of the dissociation of circulating pentameric C-reactive protein (pCRP) to its monomeric subunits (mCRP) is poorly understood. We investigated the role of conformational C-reactive protein changes in vivo. METHODS AND RESULTS: We identified mCRP in inflamed human striated muscle, human atherosclerotic plaque, and infarcted myocardium (rat and human) and its colocalization with inflammatory cells, which suggests a general causal role of mCRP in inflammation. This was confirmed in rat intravital microscopy of lipopolysaccharide-induced cremasteric muscle inflammation. Intravenous pCRP administration significantly enhanced leukocyte rolling, adhesion, and transmigration via localized dissociation to mCRP in inflamed but not noninflamed cremaster muscle. This was confirmed in a rat model of myocardial infarction. Mechanistically, this process was dependent on exposure of lysophosphatidylcholine on activated cell membranes, which is generated after phospholipase A2 activation. These membrane changes could be visualized intravitally on endothelial cells, as could the colocalized mCRP generation. Blocking of phospholipase A2 abrogated C-reactive protein dissociation and thereby blunted the proinflammatory effects of C-reactive protein. Identifying the dissociation process as a therapeutic target, we stabilized pCRP using 1,6-bis(phosphocholine)-hexane, which prevented dissociation in vitro and in vivo and consequently inhibited the generation and proinflammatory activity of mCRP; notably, it also inhibited mCRP deposition and inflammation in rat myocardial infarction. CONCLUSIONS: These results provide in vivo evidence for a novel mechanism that localizes and aggravates inflammation via phospholipase A2-dependent dissociation of circulating pCRP to mCRP. mCRP is proposed as a pathogenic factor in atherosclerosis and myocardial infarction. Most importantly, the inhibition of pCRP dissociation represents a promising, novel anti-inflammatory therapeutic strategy.

What shapes template-matching performance in cryogenic electron tomography in situ?

The detection of specific biological macromolecules in cryogenic electron tomography data is frequently approached by applying cross-correlation-based 3D template matching. To reduce computational cost and noise, high binning is used to aggregate voxels before template matching. This remains a prevalent practice in both practical applications and methods development. Here, the relation between template size, shape and angular sampling is systematically evaluated to identify ribosomes in a ground-truth annotated data set. It is shown that at the commonly used binning, a detailed subtomogram average, a sphere and a heart emoji result in near-identical performance. These findings indicate that with current template-matching practices macromolecules can only be detected with high precision if their shape and size are sufficiently different from the background. Using theoretical considerations, the experimental results are rationalized and it is discussed why primarily low-frequency information remains at high binning and that template matching fails to be accurate because similarly shaped and sized macromolecules have similar low-frequency spectra. These challenges are discussed and potential enhancements for future template-matching methodologies are proposed.

Outcomes and Complication Rates of Cuff Downsizing in the Treatment of Worsening or Persistent Incontinence After Artificial Urinary Sphincter Implantation.

PURPOSE: This study investigated the functional outcomes and complication rates of cuff downsizing for the treatment of recurrent or persistent stress urinary incontinence (SUI) in men after the implantation of an artificial urinary sphincter (AUS). METHODS: Data from our institutional AUS database spanning the period from 2009 to 2020 were retrospectively analyzed. The number of pads per day was determined, a standardized quality of life (QoL) questionnaire and the International Consultation on Incontinence Questionnaire (ICIQ) were administered, and postoperative complications according to the Clavien-Dindo classification were analyzed. RESULTS: Out of 477 patients who received AUS implantation during the study period, 25 (5.2%) underwent cuff downsizing (median age, 77 years; interquartile range [IQR], 74-81 years; median follow-up, 4.4 years; IQR, 3-6.9 years). Before downsizing, SUI was very severe (ICIQ score 19-21) or severe (ICQ score 13-18) in 80% of patients, moderate (ICIQ score 6-12) in 12%, and slight (ICIQ score 1-5) in 8%. After downsizing, 52% showed an improvement of >5 out of 21 points. However, 28% still had very severe or severe SUI, 48% had moderate SUI, and 20% had slight SUI. One patient no longer had SUI. In 52% of patients, the use of pads per day was reduced by ≥50%. QoL improved by >2 out of 6 points in 56% of patients. Complications (infections/urethral erosions) requiring device explantation occurred in 36% of patients, with a median time to event of 14.5 months. CONCLUSION: Although cuff downsizing carries a risk of AUS explantation, it can be a valuable treatment option for selected patients with persistent or recurrent SUI after AUS implantation. Over half of patients experienced improvements in symptoms, satisfaction, ICIQ scores, and pad use. It is important to inform patients about the potential risks and benefits of AUS to manage their expectations and assess individual risks.

Transcroporal Artificial Urinary Sphincter Placement With Closure of Corporal Bodies-A Long-Term Analysis of Functional Outcomes.

Objectives: An artificial urinary sphincter (AUS) is the gold standard for postoperative stress urinary incontinence (SUI). The transcorporal AUS (TC) placement constitutes the main salvage option in high-risk patients suffering from SUI with fragile urethras. The literature analyzing long-term outcomes with respect to explantation rates, continence, and erectile function is scarce. Methods and Patients: Retrospective data collection was performed in 2011. TC was applied according to a standardized protocol. TC was implanted after bulbar urethroplasty or double-cuff (DC) explantation. After TC placement, the tunica albuginea was closed in order to minimize the risk of postoperative bleedings and erectile dysfunction. Activation was performed 6 weeks postoperatively. Further follow-up (FU) was scheduled 6/24 months postoperatively and every 2 years thereafter. Primary/secondary endpoints were explantation/objective, subjective, and social continence rates. Objective or social continence was defined as the use of 0 pads/day or <2 pads/day, respectively. Thereupon, postoperative bleedings and erectile function were analyzed. Results: A total of 39 high-risk patients were available for analysis. The median age was 72 years. In total, 84.6%, 10.3%, and 2.6% had a history of radical prostatectomy, TURP, and radical cystectomy, respectively. In total, 61.5% had a history of radiation therapy of the prostate, 41% had a history of urethral surgery, and 95% had a history of double cuff explantation. The median FU was 27 months. Objective, subjective, and social continence were 54.5%, 69.7%, and 78.8%, respectively. The median pad usage was 1 pad/day [1-2.5]. Only one patient suffered from a postoperative hematoma. In total, 15.4% of the patients were able to have an erection preoperatively, compared to 7.7% after TC placement. The estimated mean explantation-free survival of the TC was 83 months in the Kaplan-Meier analysis. Conclusions: TC AUS implantation constitutes a viable salvage approach in high-risk SUI patients with a mean device survival of almost 7 years and high social continence rates of almost 80%. An intraoperative closure of the tunica albuginea after TC placement allows for very low rates of postoperative hematoma and supports postoperative erectile rigidity.

Urethral Stricture Formation Following Cuff Erosion of AMS Artificial Urinary Sphincter Devices: Implication for a Less Invasive Explantation Approach.

OBJECTIVES: The objective of this study is to describe a standardized less invasive approach in patients with artificial urinary sphincter (AUS) explantation due to cuff erosion and analyze success and urethral stricture rates out of a prospective database. Evidence regarding complication management is sparse with heterogenous results revealing high risk of urethral stricture formation despite simultaneous urethroplasty in case of AUS explantation. PATIENTS AND METHODS: Data of all patients undergoing AUS implantation due to stress urinary incontinence (SUI) in our tertiary center were prospectively collected from 2009 to 2015. In case of cuff erosion, AUS explantation was carried out in an institutional standardized strategy without urethroplasty, urethral preparation or mobilization nor urethrorrhaphy. Transurethral and suprapubic catheters were inserted for 3 weeks followed by radiography of the urethra. Further follow-up (FU) consisted of pad test, uroflowmetry, postvoiding residual urine (PVR), and radiography. Primary endpoint was urethral stricture rate. RESULTS: Out of 235 patients after AUS implantation, 24 (10.2%) experienced cuff erosion with consecutive explantation and were available for analysis. Within a median FU of 18.7 months after AUS explantation, 2 patients (8.3%) developed a urethral stricture. The remaining 22 patients showed a median Qmax of 17 ml/s without suspicion of urethral stricture. Median time to reimplantation was 4 months (IQR 3-4). CONCLUSION: We observed a considerably low stricture formation and could not prove an indication for primary urethroplasty nor delay in salvage SUI treatment possibilities. Therefore, the presented standardized less invasive explantation strategy with consequent urinary diversion seems to be safe and effective and might be recommended in case of AUS cuff erosion.

Penile Flap Inversion Vaginoplasty in Transgender Women: Contemporary Morbidity and Learning-Curve Analysis From a High-Volume Reconstructive Center.

Objectives: Numbers of PIV are rising. The aim of this study is to analyze the surgical learning-curve (LC) on the grounds of perioperative complications. Patients and Methods: 108 PIVs, performed by a single surgeon between 2015 and 2018 have been analyzed. Learning-curve analysis was based on three factors: operating time, vaginal depth and complications. Results: The median FU was 6.3 months. Median age at surgery was 36 years, median time of hormone treatment was 36 months. The median CI was 0.3 and the median BMI was 25 kg/cm3. Median CCI® was 8.08. 40.7% of the patients developed short-term complications, more than half of which were Clavien I. Overall only 1.9% had Clavien IIIb complications. There were no Clavien IV or V complications. 17.6% of patients had wound infections, 13% wound dehiscence, 9.3% introitus strictures, 13.9% suffered from atrophy of the neovagina, i.e. loss of depth or width, and 8.3% from meatus urethrae strictures. Duration of hormonal therapy, BMI and CI had no impact on surgical outcome. Age had a significant impact on CCI®, as younger patients had a higher risk for complications. Use of scrotal skin and surgeries performed had a significant influence. LC analysis via CUSUM analysis showed that after 32 surgeries, the PIV is performed safely. Conclusion: The PIV is a safe GAS-technique, associated with minor complications leading to low rates of revision surgery. Younger age, the use of scrotal skin and surgeon's experience has significant impact on complications. Duration of hormonal therapy, circumcision and BMI has no impact on complications.

Reference-free deconvolution, visualization and interpretation of complex DNA methylation data using DecompPipeline, MeDeCom and FactorViz.

DNA methylation profiling offers unique insights into human development and diseases. Often the analysis of complex tissues and cell mixtures is the only feasible option to study methylation changes across large patient cohorts. Since DNA methylomes are highly cell type specific, deconvolution methods can be used to recover cell type-specific information in the form of latent methylation components (LMCs) from such 'bulk' samples. Reference-free deconvolution methods retrieve these components without the need for DNA methylation profiles of purified cell types. Currently no integrated and guided procedure is available for data preparation and subsequent interpretation of deconvolution results. Here, we describe a three-stage protocol for reference-free deconvolution of DNA methylation data comprising: (i) data preprocessing, confounder adjustment using independent component analysis (ICA) and feature selection using DecompPipeline, (ii) deconvolution with multiple parameters using MeDeCom, RefFreeCellMix or EDec and (iii) guided biological inference and validation of deconvolution results with the R/Shiny graphical user interface FactorViz. Our protocol simplifies the analysis and guides the initial interpretation of DNA methylation data derived from complex samples. The harmonized approach is particularly useful to dissect and evaluate cell heterogeneity in complex systems such as tumors. We apply the protocol to lung cancer methylomes from The Cancer Genome Atlas (TCGA) and show that our approach identifies the proportions of stromal cells and tumor-infiltrating immune cells, as well as associations of the detected components with clinical parameters. The protocol takes slightly >3 d to complete and requires basic R skills.

Retrograde ejaculation after holmium laser enucleation of the prostate (HoLEP)-Impact on sexual function and evaluation of patient bother using validated questionnaires.

BACKGROUND: A vast body of literature has focused on erectile function after Holmium Laser Enucleation of the Prostate (HoLEP). Interestingly, retrograde ejaculation (RE), despite its frequency has sparsely been investigated. OBJECTIVES: To study patient perception and impact of RE on sexuality following HoLEP. MATERIALS AND METHODS: We retrospectively analyzed 2,131 patients undergoing HoLEP 2006-2015 at our institution. Patients were followed via standardized questionnaires namely International Index of Erectile Function (IIEF) as well as Male Sexual Health Questionnaire Ejaculatory Short Form (MSHQ-EjD-SF). Exclusion criteria were missing/follow-up <6 months, missing data on MSHQ-EjD-SF and IIEF score, resulting in 535 assessable patients. Multivariable logistic regression was employed to identify independent predictors of satisfaction with overall sex life (IIEF question 13). RESULTS: Median follow-up was 50 months (IQR: 30-78). Overall, 495 (92.5%) patients reported RE. Patients differed significantly with respect to age (P = .036), IPSS at follow-up (P = .01), and erectile function (P < .001), whereas no other statistically significant differences were observed. In multivariable logistic regression analyses, presence of RE was not independently associated with satisfaction with overall sex life (OR: 2.7, 95% CI: 0.70-10.5, P = .1). However, in the cohort of patients exhibiting RE, patients who stated "feeling bothered by RE" had lower satisfaction with overall sex life (OR: 0.23, 95% CI: 0.13-0.38, P < .001). Bother by RE varied according to erectile function and did not impact overall satisfaction in men with superior erectile function. CONCLUSIONS: RE is a very common event after HoLEP but in this retrospective analysis was not associated with overall satisfaction with sex life. Contrary, satisfaction with sex life is impaired in patients who feel bothered by RE. Proper patient selection will pose key to identify patients in which RE bother will offset the benefits of LUTS relief.