Snapshots of the Reaction Coordinate of a Thermophilic 2'-Deoxyribonucleoside/ribonucleoside Transferase.

Nucleosides are ubiquitous to life and are required for the synthesis of DNA, RNA, and other molecules crucial for cell survival. Despite the notoriously difficult organic synthesis of nucleosides, 2'-deoxynucleoside analogues can interfere with natural DNA replication and repair and are successfully employed as anticancer, antiviral, and antimicrobial compounds. Nucleoside 2'-deoxyribosyltransferase (dNDT) enzymes catalyze transglycosylation via a covalent 2'-deoxyribosylated enzyme intermediate with retention of configuration, having applications in the biocatalytic synthesis of 2'-deoxynucleoside analogues in a single step. Here, we characterize the structure and function of a thermophilic dNDT, the protein from Chroococcidiopsis thermalis (CtNDT). We combined enzyme kinetics with structural and biophysical studies to dissect mechanistic features in the reaction coordinate, leading to product formation. Bell-shaped pH-rate profiles demonstrate activity in a broad pH range of 5.5-9.5, with two very distinct pKa values. A pronounced viscosity effect on the turnover rate indicates a diffusional step, likely product (nucleobase1) release, to be rate-limiting. Temperature studies revealed an extremely curved profile, suggesting a large negative activation heat capacity. We trapped a 2'-fluoro-2'-deoxyarabinosyl-enzyme intermediate by mass spectrometry and determined high-resolution structures of the protein in its unliganded, substrate-bound, ribosylated, 2'-difluoro-2'-deoxyribosylated, and in complex with probable transition-state analogues. We reveal key features underlying (2'-deoxy)ribonucleoside selection, as CtNDT can also use ribonucleosides as substrates, albeit with a lower efficiency. Ribonucleosides are the building blocks of RNA and other key intracellular metabolites participating in energy and metabolism, expanding the scope of use of CtNDT in biocatalysis.

Unveiling the Catalytic Mechanism of a Processive Metalloaminopeptidase.

Intracellular leucine aminopeptidases (PepA) are metalloproteases from the family M17. These enzymes catalyze peptide bond cleavage, removing N-terminal residues from peptide and protein substrates, with consequences for protein homeostasis and quality control. While general mechanistic studies using model substrates have been conducted on PepA enzymes from various organisms, specific information about their substrate preferences and promiscuity, choice of metal, activation mechanisms, and the steps that limit steady-state turnover remain unexplored. Here, we dissected the catalytic and chemical mechanisms of PaPepA: a leucine aminopeptidase from Pseudomonas aeruginosa. Cleavage assays using peptides and small-molecule substrate mimics allowed us to propose a mechanism for catalysis. Steady-state and pre-steady-state kinetics, pH rate profiles, solvent kinetic isotope effects, and biophysical techniques were used to evaluate metal binding and activation. This revealed that metal binding to a tight affinity site is insufficient for enzyme activity; binding to a weaker affinity site is essential for catalysis. Progress curves for peptide hydrolysis and crystal structures of free and inhibitor-bound PaPepA revealed that PaPepA cleaves peptide substrates in a processive manner. We propose three distinct modes for activity regulation: tight packing of PaPepA in a hexameric assembly controls substrate length and reaction processivity; the product leucine acts as an inhibitor, and the high concentration of metal ions required for activation limits catalytic turnover. Our work uncovers catalysis by a metalloaminopeptidase, revealing the intricacies of metal activation and substrate selection. This will pave the way for a deeper understanding of metalloenzymes and processive peptidases/proteases.

Evasion of toll-like receptor recognition by Escherichia coli is mediated via population level regulation of flagellin production.

Uropathogenic Escherichia coli is a major cause of urinary tract infections. Analysis of the innate immune response in immortalized urothelial cells suggests that the bacterial flagellar subunit, flagellin, is key in inducing host defenses. A panel of 48 clinical uro-associated E. coli isolates recovered from either cystitis, pyelonephritis asymptomatic bacteriuria (ABU) or UTI-associated bacteraemia infections were characterized for motility and their ability to induce an innate response in urothelial cells stably transfected with a NF-κB luciferase reporter. Thirty-two isolates (67%) were identified as motile with strains recovered from cystitis patients exhibiting an uneven motility distribution pattern; seven of the cystitis isolates were associated with a > 5-fold increase in NF-κB signaling. To explore whether the NF-κB signaling response reflected antigenic variation, flagellin was purified from 14 different isolates. Purified flagellin filaments generated comparable NF-κB signaling responses, irrespective of either the source of the isolate or H-serotype. These data argued against any variability between isolates being related to flagellin itself. Investigations also argued that neither TLR4 dependent recognition of bacterial lipopolysaccharide nor growth fitness of the isolates played key roles in leading to the variable host response. To determine the roles, if any, of flagellar abundance in inducing these variable responses, flagellar hook numbers of a range of cystitis and ABU isolates were quantified. Images suggested that up to 60% of the isolate population exhibited flagella with the numbers averaging between 1 and 2 flagella per bacterial cell. These data suggest that selective pressures exist in the urinary tract that allow uro-associated E. coli strains to maintain motility, but exploit population heterogeneity, which together function to prevent host TLR5 recognition and bacterial killing.

Active site remodelling of a cyclodipeptide synthase redefines substrate scope.

Cyclodipeptide synthases (CDPSs) generate a wide range of cyclic dipeptides using aminoacylated tRNAs as substrates. Histidine-containing cyclic dipeptides have important biological activities as anticancer and neuroprotective molecules. Out of the 120 experimentally validated CDPS members, only two are known to accept histidine as a substrate yielding cyclo(His-Phe) and cyclo(His-Pro) as products. It is not fully understood how CDPSs select their substrates, and we must rely on bioprospecting to find new enzymes and novel bioactive cyclic dipeptides. Here, we developed an in vitro system to generate an extensive library of molecules using canonical and non-canonical amino acids as substrates, expanding the chemical space of histidine-containing cyclic dipeptide analogues. To investigate substrate selection we determined the structure of a cyclo(His-Pro)-producing CDPS. Three consecutive generations harbouring single, double and triple residue substitutions elucidated the histidine selection mechanism. Moreover, substrate selection was redefined, yielding enzyme variants that became capable of utilising phenylalanine and leucine. Our work successfully engineered a CDPS to yield different products, paving the way to direct the promiscuity of these enzymes to produce molecules of our choosing.

A Systematic Review and Meta-analysis of Adjuncts to Minimally Invasive Treatment of Urethral Stricture in Men.

CONTEXT: Urethral stricture disease (USD) is initially managed with minimally invasive techniques such as urethrotomy and urethral dilatation. Minimally invasive techniques are associated with a high recurrence rate, especially in recurrent USD. Adjunctive measures, such as local drug injection, have been used in an attempt to reduce recurrence rates. OBJECTIVE: To systematically review evidence for the efficacy and safety of adjuncts used alongside minimally invasive treatment of USD. EVIDENCE ACQUISITION: A systematic review of the literature published between 1990 and 2020 was conducted in accordance with the PRISMA checklist. EVIDENCE SYNTHESIS: A total of 26 studies were included in the systematic review, from which 13 different adjuncts were identified, including intralesional injection (triamcinolone, n = 135; prednisolone, n = 58; mitomycin C, n = 142; steroid-mitomycin C-hyaluronidase, n = 103, triamcinolone-mitomycin C-N-acetyl cysteine, n = 50; platelet-rich plasma, n = 44), intraluminal instillation (mitomycin C, n = 20; hyaluronic acid and carboxymethylcellulose, n = 70; captopril, n = 37; 192-iridium brachytherapy, n = 10), application via a lubricated catheter (triamcinolone, n = 124), application via a coated balloon (paclitaxel, n = 106), and enteral application (tamoxifen, n = 30; deflazacort, n = 36). Overall, 13 randomised controlled trials were included in the meta-analysis. Use of any adjunct was associated with a lower rate of USD recurrence (odds ratio [OR] 0.37, 95% confidence interval [CI] 0.27-0.50; p <  0.001) compared to no adjunct use. Of all the adjuncts, mitomycin C was associated with the lowest rate of USD recurrence (intralesional injection: OR 0.23, 95% CI 0.11-0.48; p <  0.001; intraluminal injection: OR 0.11, 95% CI 0.02-0.61; p =  0.01). Urinary tract infection (2.9-14%), bleeding (8.8%), and extravasation (5.8%) were associated with steroid injection; pruritis of the urethra (61%) occurred after instillation of captopril; mild gynaecomastia (6.7%) and gastrointestinal side effects (6.7%) were associated with oral tamoxifen. CONCLUSIONS: Adjuncts to minimally invasive treatment of USD appear to lower the recurrence rate and are associated with a low adjunct-specific complication rate. However, the studies included were at high risk of bias. Mitomycin C is the adjunct supported by the highest level of evidence. PATIENT SUMMARY: We reviewed studies on additional therapies (called adjuncts) to minimally invasive treatments for narrowing of the urethra in men. Adjuncts such as mitomycin C injection result in a lower recurrence rate compared to no adjunct use. The use of adjuncts appeared to be safe and complications are uncommon; however, the studies were small and of low quality.

British Association of Urological Surgeons (BAUS) consensus document: management of bladder and ureteric injury.

Injuries to the bladder and ureter are uncommon but usually require prompt urological management. Due to their infrequent nature, Urologists maybe unfamiliar with managing these acute problems and may not work in specialist centres with readily available expertise in open and abdominal surgery. We aim to provide advice in the form of a consensus statement led by the Female, Neurological and Urodynamic Urology (FNUU) Section of the British Association of Urological Surgeons (BAUS), in consultation with BAUS members and consultants working in units throughout the UK, to create a comprehensive management pathway and a series of statements to aid clinicians.

Current process and outcomes of the surgical management of LUTS due to benign prostatic enlargement: how consistent are we? - results from the multi-institutional audit of surgical management of BPE (AuSuM BPE) in the United Kingdom.

OBJECTIVE: In view of changing landscape of surgical treatment for LUTS secondary to BPE, this audit was undertaken to assess key aspects of the processes and outcomes of the current interventional treatments for BPE, across different units in the UK. MATERIALS AND METHOD: A multi-institutional snapshot audit was conducted for patients undergoing interventions for LUTS/BPE over 8-week period. Using Delphi process two-part proforma was designed to capture data. RESULTS: 529 patients were included across 20 NHS trusts in England and Wales. Median age was 73 years. Indications for surgery were acute retention (47%) and LUTS (45%). 80% of patients had prior medical therapy. TURP formed the commonest procedure. 27% patients had <23 hour hospital stay. Immediate (21%) and delayed (18%) complications were Clavien-Dindo <2 category. High proportion of patients reported residual symptoms. Type and indication of surgery were significant predictor of complications, length of stay and failure of TWOC outcomes, on multivariate analyses. There were variations in departmental processes, 50% centres used PROMs. CONCLUSION: Monopolar TURP still remains the commonest intervention for BPE. Most departments are adopting newer technologies. The audit identified opportunities for development of consistent, effective and patient centric practices as well as need for large-scale focused studies.

Complications of synthetic mesh inserted for stress urinary incontinence.

OBJECTIVE: To provide an update on the literature regarding the management of complications secondary to synthetic mesh placed to treat stress urinary incontinence (SUI). METHODS: We performed a systematic review of the literature using a multi-database structured search within OVID, the Medical Literature Analysis and Retrieval System Online (MEDLINE), the Excerpta Medica dataBASE (EMBASE) and Cochrane library databases; using the keywords: urology, incontinence, mesh and surgery. RESULTS: Several million synthetic polypropylene meshes have been inserted into women worldwide to manage SUI. Unfortunately, a significant number of women have now reported life-changing complications. We found a paucity of studies, heterogeneity of cohorts, poor long-term follow-up, and lack of evidence on the effective management of mesh-related complications. CONCLUSIONS: The contemporary evidence is low-level and often contradictory, which prevents robust recommendations regarding treatment. A prospective registry will be required to generate meaningful outcome data and help in the complex management of patients who have mesh-related complications.

Do we need better information to advise women with stress incontinence on their choice of surgery? Report from the ICI-RS 2018.

AIMS: The regulatory warnings about the safety of the synthetic midurethral slings (MUS) had a significant effect on how patients and physicians approach surgical management of stress urinary incontinence (SUI). In this changing landscape, the purpose of this research Think Tank (TT) was to provide an update of the current knowledge about the safety and efficacy of SUI surgery, to review patient goals and expectations and to identify factors affecting the decision making for surgery. METHODS: This is a consensus report of the proceedings of TT3: "Do we need better information to advise women with stress incontinence on their choice of surgery?" from the annual International Consultation on Incontinence-Research Society (ICI-RS), June 2018. RESULTS: Despite the body of evidence supporting the continued use of MUS, the short follow-up of most of the studies and the lack of "real life" data regarding pain and sexual dysfunction make the development of recommendations challenging. Women with SUI are often happy to "trade" efficacy for a procedure with less associated morbidity and therefore it is not always the procedure with the highest success rate that is ultimately chosen. However, a number of factors influence treatment decision and there is limited evidence about what level of all these factors women are willing to tolerate for a given success rate, or how much success they are willing to trade for a lower complication rate. CONCLUSIONS: The ICI-RS proposed research questions which may be able to assist in improving the counseling and management of women with SUI.

Patient-reported outcomes and urodynamic findings in men with persistent lower urinary tract symptoms following robot-assisted radical prostatectomy.

AIMS: To evaluate the patient-reported outcome measures (PROMs) and urodynamic findings in men seeking intervention for lower urinary tract symptoms (LUTS) after robotic-assisted radical prostatectomy (RARP) in a regional referral center for continence surgery. METHODS: Consecutive men with post-RARP LUTS, who were referred for specialist evaluation and urodynamics between December 2012 and October 2017, were evaluated. Men were invited to complete the International Consultation on Incontinence Questionnaire on Male Lower Urinary Tract Symptoms Long Form (ICIQ-MLUTS) pre-operatively and at 6, 12 and 18 months post-RARP. RESULTS: In total 64/860 (7.4%) men post-RARP were referred for specialist evaluation. There was a significant increase in total ICIQ-MLUTS and bother scores at 6, 12 and 18 months compared with the baseline in these men (P < 0.001 and P < 0.05, respectively). Urodynamics identified 41/64 (64%) had urodynamic stress incontinence (USI) only, 2/64 (3%) had detrusor overactivity (DO) only and 11/64 (17%) had a combination of USI and DO. Of those referred to a continence specialist 29/64 (45%) underwent a continence procedure. CONCLUSIONS: Patients with bothersome LUTS post-RARP have higher baseline ICIQ-MLUTs scores and significant worsening of total scores at all time points compared with the baseline. Routine use of PROMs may identify patients at risk of bothersome symptoms after RARP and prompt earlier referral for further management of their LUTS. Urodynamic evaluation revealed that the most common finding was pure stress incontinence but the range of urodynamic diagnoses highlights the need to perform urodynamics before making treatment decisions for men with LUTS post-RARP.

Detailed analysis of patient-reported lower urinary tract symptoms and effect on quality of life after robotic radical prostatectomy.

OBJECTIVE: To prospectively evaluate short- to medium-term patient-reported lower urinary tract symptoms (LUTS) and their effect on health-related quality of life (HRQoL) using validated questionnaires in a large cohort of patients following robotic-assisted radical prostatectomy (RARP) for prostate cancer. MATERIALS AND METHODS: HRQoL and LUTS outcomes were prospectively assessed in 357 consecutive men undergoing RARP at a single center from 2012 to 2015 using the functional assessment of cancer therapy-prostate (FACT-P) and the international consultation on incontinence modular questionnaire-male LUTS (ICIQ-MLUTS). Questionnaires were administered at baseline, 6, 12, and 18 months. Data were analyzed using paired t-tests and ANOVA. RESULTS: Questionnaire completion rates were high (over 60% of eligible men completed 18-month follow-up). Mean Total FACT-P did not significantly change after RARP: 125.95 (standard deviation [SD] = 19.82) at baseline and 125.86 (SD = 21.14) at 18-months (P = 0.55). Mean total ICIQ-MLUTS also remained unchanged: 18.69 (SD = 10.70) at baseline and 18.76 (SD = 11.33) at 18-months (P = 0.11). Mean voiding score significantly reduced from 10.34 (SD = 5.78) at baseline to 6.33 (SD = 3.99) at 6 months after RARP (P<0.001). A reciprocal significant increase in storage score was observed: 5.34 (SD = 4.26) at baseline, 9.65 (SD = 5.71) at 6 months (P<0.001). Subanalyses of ICIQ-MLUTS scores revealed increases in storage symptoms were exclusively within urinary incontinence domains and included significant increases in both urge and stress urinary incontinence scores. CONCLUSION: Overall, patient-reported outcome measures evaluating HRQoL and LUTS do not significantly change after RARP. Detailed analysis reveals significant changes within LUTS domains do occur after surgery which could be overlooked if only total LUTS scores are reported.

Can filling phase urodynamic parameters predict the success of the bulbar artificial urinary sphincter in treating post-prostatectomy incontinence?

OBJECTIVE: To evaluate whether filling phase urodynamic parameters can predict the success of the artificial urinary sphincter (AUS) in treating post-prostatectomy incontinence (PPI). MATERIALS AND METHODS: We reviewed the pre-AUS urodynamics of 99 patients with PPI at two tertiary referral centers. We documented the peak DO pressure (Pdet ), capacity, and compliance (C). We defined success as patient-reported continence or only using one safety pad. Patients' perception of improvement was assessed using the PGI-I score. RESULTS: Sixty-eight percent (n = 68) of patients had a successful outcome. The mean compliance for the "success" and "failure" group was 112.3 mL/cmH2 O (±119.7) and 34.1 mL/cmH2 O (±36.2), respectively. Fifty-five percent (17/31) of patients in the "failure" group demonstrated DO(Pdet = 36.2 ± 18.2 cmH2 O) compared to 18% (12/68) in the success group. The differences between the two groups in Pdet and compliance were statistically significant (all P < 0.01). There was, however, no statistical difference between the mean cystometric capacities of patients in the two outcome groups. Thirteen out of 18 (72%) patients who had radiotherapy had a poor outcome ("success" group only 15% [9/59]). These results were used to develop a nomogram for the probability of AUS success. A good inverse correlation (r = -0.65) was demonstrated between the probability of AUS success as deduced from the nomogram and PGI-I score post-AUS implantation CONCLUSION: Compliance and Pdet are predictors of outcome following AUS implantation for PPI. We have developed and internally validated a nomogram that may be used to determine an individualized likelihood of AUS success. This nomogram may be used as a counseling tool to objectively set realistic expectations of continence post-AUS implantation.

Regional Isolation Drives Bacterial Diversification within Cystic Fibrosis Lungs.

Bacterial lineages that chronically infect cystic fibrosis (CF) patients genetically diversify during infection. However, the mechanisms driving diversification are unknown. By dissecting ten CF lung pairs and studying ∼12,000 regional isolates, we were able to investigate whether clonally related Pseudomonas aeruginosa inhabiting different lung regions evolve independently and differ functionally. Phylogenetic analysis of genome sequences showed that regional isolation of P. aeruginosa drives divergent evolution. We investigated the consequences of regional evolution by studying isolates from mildly and severely diseased lung regions and found evolved differences in bacterial nutritional requirements, host defense and antibiotic resistance, and virulence due to hyperactivity of the type 3 secretion system. These findings suggest that bacterial intermixing is limited in CF lungs and that regional selective pressures may markedly differ. The findings also may explain how specialized bacterial variants arise during infection and raise the possibility that pathogen diversification occurs in other chronic infections characterized by spatially heterogeneous conditions.

Differences in urodynamic voiding variables recorded by conventional cystometry and ambulatory monitoring in symptomatic women.

OBJECTIVES: To determine whether there are differences in pressure and flow measurements between conventional cystometry (CONV) and ambulatory urodynamic monitoring (AMB) in women with overactive bladder syndrome and urinary incontinence. MATERIALS AND METHODS: Retrospective study which included female subjects who underwent both CONV (with saline filling medium) and AMB, separated by less than 24 months, not using medication active on the lower urinary tract and without history of prior pelvic surgery. Both tests were carried out in compliance with the International Continence Society standards. The paired Student's t test was used to compare continuous variables. Bland-Altman statistics were used to assess the agreement of each variable between both studies. RESULTS: Thirty women with a median (range) age of 50 (14 - 73) years met the inclusion criteria. AMB was carried out at a mean (SD) of 11 (6) months after CONV. Measurements of pves and pabd at the end of filling, and Qmax were significantly higher from AMB recordings. There were no differences in pdet at the end of filling, pdetQmax or pdetmax during voiding, nor significant difference in Vvoid. CONCLUSIONS: We provide previously undocumented comparative voiding data between CONV and AMB for patients who most commonly require both investigations. Our findings show higher values of Qmax but similar values of pdetQmax measured by AMB which may partly reflect an overall lower catheter caliber, physiological filling but perhaps also more 'normal' voiding conditions.

Differences in urodynamic voiding variables recorded by conventional cystometry and ambulatory monitoring in symptomatic women

Objectives To determine whether there are differences in pressure and flow measurements between conventional cystometry (CONV) and ambulatory urodynamic monitoring (AMB) in women with overactive bladder syndrome and urinary incontinence. Materials and Methods Retrospective study which included female subjects who underwent both CONV (with saline filling medium) and AMB, separated by less than 24 months, not using medication active on the lower urinary tract and without history of prior pelvic surgery. Both tests were carried out in compliance with the International Continence Society standards. The paired Student’s t test was used to compare continuous variables. Bland-Altman statistics were used to assess the agreement of each variable between both studies. Results Thirty women with a median (range) age of 50 (14 - 73) years met the inclusion criteria. AMB was carried out at a mean (SD) of 11 (6) months after CONV. Measurements of pves and pabd at the end of filling, and Qmax were significantly higher from AMB recordings. There were no differences in pdet at the end of filling, pdetQmax or pdetmax during voiding, nor significant difference in Vvoid. Conclusions We provide previously undocumented comparative voiding data between CONV and AMB for patients who most commonly require both investigations. Our findings show higher values of Qmax but similar values of pdetQmax measured by AMB which may partly reflect an overall lower catheter caliber, physiological filling but perhaps also more ‘normal’ voiding conditions. .

Auricular acupuncture: a novel treatment for vasomotor symptoms associated with luteinizing-hormone releasing hormone agonist treatment for prostate cancer.

OBJECTIVES: To evaluate the role of auricular acupuncture (AA) in men receiving luteinizing-hormone releasing hormone (LHRH) analogues for carcinoma of the prostate, as vasomotor symptoms can affect the quality of life in such men, and similar symptoms in postmenopausal women have been successfully treated with AA. PATIENTS AND METHODS: In all, 60 consecutive patients with prostate cancer and on LHRH agonist treatment (median age 74 years, range 58-83) consented to weekly AA for 10 weeks. The validated 'Measure Yourself Concerns and Well-Being' questionnaire (a six-point scale to assess symptom severity) was used to assess concerns and well-being before and after treatment. RESULTS: All men completed the treatment with no adverse events recorded, apart from transient exacerbation of symptoms in two men; 95% of patients reported a decrease in the severity of symptoms, from a mean 5.0 to 2.1 (Student's t-test, P < 0.01). CONCLUSIONS: The symptomatic improvement was at levels comparable with that from pharmacotherapy, and cost analysis showed AA to be a viable alternative. Larger randomized studies are needed to fully evaluate AA against more conventional treatments, and these are planned.

Categorization of obstruction using noninvasive pressure flow measurements: sensitivity to change following prostatectomy.

PURPOSE: We determined whether categorizing men with lower urinary tract symptoms using a noninvasive pressure flow nomogram is sensitive to change following the removal of obstruction. MATERIALS AND METHODS: A prospective cohort of men undergoing transurethral prostate resection was recruited, of whom 143 (69%) underwent noninvasive pressure flow study using the penile cuff technique before and 4 months following surgery. Cuff pressure required to interrupt voiding, estimated isovolumetric bladder pressure and maximum flow rate were recorded during a single void. Values were plotted on a nomogram categorizing cases as obstructed (upper left quadrant), not obstructed (lower right quadrant) or diagnosis uncertain (upper right and lower left quadrants). Changes in maximum flow rate, cuff pressure required to interrupt voiding and nomogram position following transurethral prostate resection were then analyzed. RESULTS: Transurethral prostate resection resulted in an improved flow rate for all diagnostic groups, which was highest for obstructed cases with a mean +/- SD increase of 11 +/- 6 ml second(-1) (p <0.01). Men categorized with obstruction and those placed in the upper right quadrant showed significant decreases in cuff pressure required to interrupt voiding following transurethral prostate resection with a mean decrease of -45 +/- 35 and -48 +/- 32 cm H(2)O, respectively (p <0.01). The number of cases classified as not obstructed increased from 28 (19%) preoperatively to 114 (80%) after transurethral prostate resection. CONCLUSIONS: Sensitivity to change following the removal of obstruction further validates the usefulness of noninvasive measurement of bladder pressure by the penile cuff test and the categorization of obstruction by the noninvasive nomogram. Decreased isovolumetric bladder pressure following transurethral prostate resection may reflect a return to normal detrusor contraction strength.

Predicting the outcome of prostatectomy using noninvasive bladder pressure and urine flow measurements.

OBJECTIVES: To determine whether categorisation of bladder outlet obstruction (BOO) using measurements of bladder pressure and urine flow obtained by a novel noninvasive medical device (the penile cuff test) improves prediction of outcome from endoscopic prostatectomy (TURP). METHODS: A consecutive cohort of 208 men undergoing TURP following standard assessment in our institution was recruited, and 179 (86%) completed the protocol. Each subject underwent a penile cuff test prior to surgery; outcome was assessed by change in IPSS at 4 mo. The proportion of men with good outcome (>50% reduction in IPSS) was compared according to categorisation by noninvasive bladder pressure and urine flow measurements. RESULTS: The cuff test was completed by 93% of men with 2% experiencing an adverse event. Men categorised as having BOO by the test (37% of total) had an 87% chance of a good outcome from TURP (p<0.01), whilst of those deemed not obstructed (19% of total) 56% experienced good outcome (p<0.01). For the remaining men not categorised in these two groups, 77% had good outcome, which was identical to the result of the cohort as a whole (77%, p=NS). CONCLUSIONS: Urodynamic categorisation using measurements obtained by the noninvasive penile cuff test improves prediction of outcome for men with LUTS undergoing TURP. This finding together with the ease and acceptability of the test suggest its suitability for office-based clinical use to assist men and their physicians in the selection for surgical treatment for relief of LUTS.