Rituximab or Cyclosporine in the Treatment of Membranous Nephropathy.

BACKGROUND: B-cell anomalies play a role in the pathogenesis of membranous nephropathy. B-cell depletion with rituximab may therefore be noninferior to treatment with cyclosporine for inducing and maintaining a complete or partial remission of proteinuria in patients with this condition. METHODS: We randomly assigned patients who had membranous nephropathy, proteinuria of at least 5 g per 24 hours, and a quantified creatinine clearance of at least 40 ml per minute per 1.73 m2 of body-surface area and had been receiving angiotensin-system blockade for at least 3 months to receive intravenous rituximab (two infusions, 1000 mg each, administered 14 days apart; repeated at 6 months in case of partial response) or oral cyclosporine (starting at a dose of 3.5 mg per kilogram of body weight per day for 12 months). Patients were followed for 24 months. The primary outcome was a composite of complete or partial remission of proteinuria at 24 months. Laboratory variables and safety were also assessed. RESULTS: A total of 130 patients underwent randomization. At 12 months, 39 of 65 patients (60%) in the rituximab group and 34 of 65 (52%) in the cyclosporine group had a complete or partial remission (risk difference, 8 percentage points; 95% confidence interval [CI], -9 to 25; P = 0.004 for noninferiority). At 24 months, 39 patients (60%) in the rituximab group and 13 (20%) in the cyclosporine group had a complete or partial remission (risk difference, 40 percentage points; 95% CI, 25 to 55; P<0.001 for both noninferiority and superiority). Among patients in remission who tested positive for anti-phospholipase A2 receptor (PLA2R) antibodies, the decline in autoantibodies to anti-PLA2R was faster and of greater magnitude and duration in the rituximab group than in the cyclosporine group. Serious adverse events occurred in 11 patients (17%) in the rituximab group and in 20 (31%) in the cyclosporine group (P = 0.06). CONCLUSIONS: Rituximab was noninferior to cyclosporine in inducing complete or partial remission of proteinuria at 12 months and was superior in maintaining proteinuria remission up to 24 months. (Funded by Genentech and the Fulk Family Foundation; MENTOR ClinicalTrials.gov number, NCT01180036.).

Very long-term follow-up of autologous pubovaginal fascia slings in women with stress urinary incontinence.

INTRODUCTION AND HYPOTHESIS: The objective was to report on the very long-term outcome of a published series of autologous pubovaginal slings (PVS) in women with stress urinary incontinence (SUI). METHODS: Following institutional review board approval, a cohort of well characterized, non-neurogenic women who underwent an autologous PVS (primary [PVS1] and secondary [PVS2]) for SUI was re-evaluated for their very long-term outcome status. Data collected included demographics, validated questionnaires (Urogenital Distress Inventory - short form [UDI-6], Incontinence Impact Questionnaire - short form 7, quality of life), SUI retreatment/operations, and subjective patient-reported SUI improvement (%) and symptom recurrence. The primary outcome was success defined as UDI-6 question 3 (SUI) ≤ 1 and no SUI retreatment/operation. Patients not seen in clinic for 2 years were contacted via a standardized phone interview. RESULTS: From 83 patients with 7-year intermediate follow-up data, 34 (PVS1 = 18, PVS2 = 16) had very long-term follow-up based on clinic visit (7) or phone interviews (27). Those lost to follow-up (49), including 5 deceased, did not differ in demographics and intermediate outcomes from the followed cohort, but lived further away (>75 miles). At a mean age of 74 years, and with a median follow-up of 14.5 years, 53% met the success criteria (PVS1 = 44%, PVS2 = 63%). Mean postoperative questionnaire scores did not differ significantly between intermediate and very long-term follow-ups, and long-term outcomes between PVS1 and PVS2 remained similar. CONCLUSIONS: A majority of women with long-term follow-up after PVS for primary and secondary SUI remained successful more than 14 years after their surgery. Both groups, PVS1 and PVS2, fared equally well, confirming the durability of PVS as a treatment alternative for SUI.

Differentiation of renal masses with multi-parametric MRI: the de Silva St George classification scheme.

PURPOSE: To develop a system for multi-parametric MRI to differentiate benign from malignant solid renal masses and assess its accuracy compared to the gold standard of histopathological diagnosis. METHODS: This is a retrospective analysis of patients who underwent 3 Tesla mpMRI for further assessment of small renal tumours with specific scanning and reporting protocol incorporating T2 HASTE signal intensity, contrast enhancement ratios, apparent diffusion coefficient and presence of microscopic/macroscopic fat. All MRIs were reported prior to comparison with histopathologic diagnosis and a reporting scheme was developed. 2 × 2 contingency table analysis (sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV)), Fisher Exact test were used to assess the association between suspicion of malignancy on mpMRI and histopathology, and descriptive statistics were performed. RESULTS: 67 patients were included over a 5-year period with a total of 75 renal masses. 70 masses were confirmed on histopathology (five had pathognomonic findings for angiomyolipomas; biopsy was therefore considered unethical, so these were included without histopathology). Three patients were excluded due to a non-diagnostic result, non-standardised imaging and one found to be an organising haematoma rather than a mass. Therefore 72 cases were included in analysis (in 64 patients, with seven patients having multiple tumours). Unless otherwise specified, all further statistics refer to individual tumours rather than patients. 52 (72.2%) were deemed 'suspicious or malignant' and 20 (27.8%) were deemed 'benign' on mpMRI. 51 cases (70.8%) had renal cell carcinoma confirmed. The sensitivity, NPV, specificity and PPV for MRI for detecting malignancy were 96.1%, 90%, 85.7% and 94.2% respectively, Fisher's exact test demonstrated p < 0.0001 for the association between suspicion of malignancy on MRI and histopathology. CONCLUSION: The de Silva St George classification scheme performed well in differentiating benign from malignant solid renal masses, and may be useful in predicting the likelihood of malignancy to determine the need for biopsy/excision. Further validation is required before this reporting system can  be recommended for clinical use.

The diagnostic utility of diffusion weighted MRI imaging and ADC ratio to distinguish benign from malignant renal masses: sorting the kittens from the tigers.

BACKGROUND: MRI is playing an increasing role in risk stratification and non-invasive diagnosis of the undifferentiated small renal mass. This study was designed to assess the reliability of MRI in diagnostic evaluation of renal masses, specifically characterising lesions with diffusion weighted imaging (DWI) and apparent diffusion coefficient (ADC) values. METHODS: This is a retrospective analysis of patients undergoing MRI as part of their clinical workup for a renal mass suspicious for renal cell carcinoma (RCC) on CT or ultrasound followed by biopsy and/or surgical excision. All cases were conducted on 3 Tesla MRI, with conventional breath-held sequences, DWI and dynamic contrast enhanced phases. Tumour regions of interest were evaluated on ADC maps and compared with T2 weighted and post-contrast images. RESULTS: Of the 66 renal tumours included, 33 (50.0%) were Clear Cell RCC, 11 (16.7%) were Oncocytoma, nine (13.6%) were Angiomyolipoma (AML), nine (13.6%) were Papillary RCC and four (6.1%) were Chromophobe RCC. Oncocytoma had the largest ADC values, significantly larger than AMLs and all RCC subtypes (p < 0.001). The average ADC value was also significantly larger in Clear Cell RCCs compared to AMLs, and other RCC subtypes (p < 0.001). CONCLUSIONS: MRI with DWI/ADC imaging may aid the differentiation of oncocytomas from RCCs and stratify RCC subtypes, Further studies are required to validate these findings. TRIAL REGISTRATION: Not applicable/retrospective study.

Robust CTCF-Based Chromatin Architecture Underpins Epigenetic Changes in the Heart Failure Stress-Gene Response.

BACKGROUND: The human genome folds in 3 dimensions to form thousands of chromatin loops inside the nucleus, encasing genes and cis-regulatory elements for accurate gene expression control. Physical tethers of loops are anchored by the DNA-binding protein CTCF and the cohesin ring complex. Because heart failure is characterized by hallmark gene expression changes, it was recently reported that substantial CTCF-related chromatin reorganization underpins the myocardial stress-gene response, paralleled by chromatin domain boundary changes observed in CTCF knockout. METHODS: We undertook an independent and orthogonal analysis of chromatin organization with mouse pressure-overload model of myocardial stress (transverse aortic constriction) and cardiomyocyte-specific knockout of Ctcf. We also downloaded published data sets of similar cardiac mouse models and subjected them to independent reanalysis. RESULTS: We found that the cardiomyocyte chromatin architecture remains broadly stable in transverse aortic constriction hearts, whereas Ctcf knockout resulted in ≈99% abolition of global chromatin loops. Disease gene expression changes correlated instead with differential histone H3K27-acetylation enrichment at their respective proximal and distal interacting genomic enhancers confined within these static chromatin structures. Moreover, coregulated genes were mapped out as interconnected gene sets on the basis of their multigene 3D interactions. CONCLUSIONS: This work reveals a more stable genome-wide chromatin framework than previously described. Myocardial stress-gene transcription responds instead through H3K27-acetylation enhancer enrichment dynamics and gene networks of coregulation. Robust and intact CTCF looping is required for the induction of a rapid and accurate stress response.

Management of Pelvic Organ Prolapse After Radical Cystectomy.

PURPOSE OF REVIEW: This article explores the anatomy, management options, and outcomes of pelvic organ prolapse with a female cystectomy patient. RECENT FINDINGS: There is a lack of data on surgical management outcomes for prolapse following radical cystectomy. However, most case series from tertiary referral centers show reasonable results irrespective of route of repair. As expected, the surgical planes and the reorientation of the bowel loop for urinary diversion makes any pelvic reconstruction a potential hazard and requires a high level of expertise and counseling to the patient in regard to the management of expectations. Pelvic organ prolapse following radical cystectomy is uncommon but presents a significant challenge to the reconstructive surgeon.

Position statement: a clinical approach to the management of adult non-neurogenic overactive bladder.

INTRODUCTION: Overactive bladder (OAB) is a highly prevalent medical condition that has an adverse impact on various health-related quality-of-life domains, including a significant psychosocial and financial burden. This position statement, formulated by members of the Urological Society of Australia and New Zealand and the UroGynaecological Society of Australasia, summarises the current recommendations for clinical diagnosis and treatment strategies in patients with non-neurogenic OAB, and guides clinicians in the decision-making process for managing the condition using evidence-based medicine. Main recommendations: Diagnosis and initial management should be based on thorough clinical history, examination and basic investigations to exclude underlying treatable causes such as urinary tract infection and urological malignancy. Initial treatment strategies for OAB involve conservative management with behavioural modification and bladder retraining. Second-line management involves medical therapy using anticholinergic or ß3 agonist drugs provided there is adequate assessment of bladder emptying. If medical therapy is unsuccessful, further investigations with urodynamic studies and cystourethroscopy are recommended to guide further treatment. Intravesical botulinum toxin and sacral neuromodulation should be considered in medical refractory OAB. Changes in management as a result of this statement: OAB is a constellation of urinary symptoms and is a chronic condition with a low likelihood of cure; managing patient expectations is essential because OAB is challenging to treat. At present, the exact pathogenesis of OAB remains unclear and it is likely that there are multiple factors involved in this disease complex. Current medical treatment remains far from ideal, although minimally invasive surgery can be effective. Further research into the pathophysiology of this common condition will hopefully guide future developments in disease management.

Single Molecule Trapping and Sensing Using Dual Nanopores Separated by a Zeptoliter Nanobridge.

There is a growing realization, especially within the diagnostic and therapeutic community, that the amount of information enclosed in a single molecule can not only enable a better understanding of biophysical pathways, but also offer exceptional value for early stage biomarker detection of disease onset. To this end, numerous single molecule strategies have been proposed, and in terms of label-free routes, nanopore sensing has emerged as one of the most promising methods. However, being able to finely control molecular transport in terms of transport rate, resolution, and signal-to-noise ratio (SNR) is essential to take full advantage of the technology benefits. Here we propose a novel solution to these challenges based on a method that allows biomolecules to be individually confined into a zeptoliter nanoscale droplet bridging two adjacent nanopores (nanobridge) with a 20 nm separation. Molecules that undergo confinement in the nanobridge are slowed down by up to 3 orders of magnitude compared to conventional nanopores. This leads to a dramatic improvement in the SNR, resolution, sensitivity, and limit of detection. The strategy implemented is universal and as highlighted in this manuscript can be used for the detection of dsDNA, RNA, ssDNA, and proteins.

Long-term functional outcomes following non-radiated urethrovaginal fistula repair.

OBJECTIVE: To review long-term functional outcomes after urethrovaginal fistula (UVF) repair. MATERIALS AND METHODS: Following IRB approval, women who underwent transvaginal non-irradiated UVF repair with minimum 6-month follow-up were reviewed. Surgical outcomes were assessed by validated questionnaires: UDI-6, IIQ-7, FSFI and visual analogue scale for QoL. Two groups were compared: (1) synthetic sling-related versus (2) non-sling-related UVF. Descriptive statistics were applied with p < 0.05 for significance. RESULTS: From 1996 to 2013, 18 patients underwent UVF repair, with a mean age of 46 years (range 20-66), BMI 29 (range 21-42) and mean follow-up at 52 months (range 9-142). Overall repair success rate was 95%. Prior failed UVF repair was recorded in 11 women (61%). Statistical differences noted for Q4: 1.9 versus 0.8 (p = 0.03) and Q5: 1.3 versus 0 (p = 0.02) and VAS between the two groups, favoring the non-sling group; 1.5 (0.6) versus 5 (4) (p = 0.05). No differences in IIQ-7 were noted between the two groups (p = 0.09). Of the 18 patients, 5 remained sexually active and of those, 2 responded to FSFI (40%) with low scores. Reoperation rate was 33% (6 women) with 3 requiring periurethral-bulking agent for recurrent SUI, 2 transurethral laser for residual urethral sling mesh strands and 1 urethral dilation. CONCLUSION: This large contemporary series of non-radiated UVF indicates a satisfactory outcome in UVF closure repair at a mean 4- to 5-year long-term follow-up, with the synthetic sling-related group performing worse.

Algorithms that eliminate the effects of calibration artefact and trial-imposed offsets of Masimo oximeter in BOOST-NZ trial.

The displayed readings of Masimo pulse oximeters used in the Benefits Of Oxygen Saturation Targeting (BOOST) II and related trials in very preterm babies were influenced by trial-imposed offsets and an artefact in the calibration software. A study was undertaken to implement new algorithms that eliminate the effects of offsets and artefact. In the BOOST-New Zealand trial, oxygen saturations were averaged and stored every 10 s up to 36 weeks' post-menstrual age. Two-hundred and fifty-seven of 340 babies enrolled in the trial had at least two weeks of stored data. Oxygen saturation distribution patterns corresponding with a +3 % or -3 % offset in the 85-95 % range were identified together with that due to the calibration artefact. Algorithms involving linear and quadratic interpolations were developed, implemented on each baby of the dataset and validated using the data of a UK preterm baby, as recorded from Masimo oximeters with the original software and a non-offset Siemens oximeter. Saturation distributions obtained were compared for both groups. There were a flat region at saturations 85-87 % and a peak at 96 % from the lower saturation target oximeters, and at 93-95 and 84 % respectively from the higher saturation target oximeters. The algorithms lowered the peaks and redistributed the accumulated frequencies to the flat regions and artefact at 87-90 %. The resulting distributions were very close to those obtained from the Siemens oximeter. The artefact and offsets of the Masimo oximeter's software had been addressed to determine the true saturation readings through the use of novel algorithms. The implementation would enable New Zealand data be included in the meta-analysis of BOOST II trials, and be used in neonatal oxygen studies.

Abdominal mesh sacrocolpopexy without promontory fixation: initial results of the peritoneocolpopexy technique.

PURPOSE: We present our experience and early outcomes using a new technique for mesh anchorage during open sacrocolpopexy called peritoneocolpopexy. MATERIALS AND METHODS: A prospective review of patients from an institutional review board approved sacrocolpopexy database who underwent mesh peritoneocolpopexy was performed. Data included complications, validated questionnaires, pelvic organ prolapse quantification examination and associated outcomes. After placement of a Marlex® mesh anteriorly and posteriorly to the vaginal apex, the tail of the mesh is positioned in a peritoneal groove extending toward the promontory. The mesh is secured to surrounding tissues (peritoneum and fat underneath) with 2 running 2-zero V-Loc™ 180 (unidirectional barbed delayed absorbable) sutures placed on either side of the mesh tail well below the promontory. RESULTS: Fourteen patients were identified from our prospective database. Mean age and followup were 60.5 years (range 28 to 82) and 19.6 months (range 7 to 38.3), respectively. Mean preoperative C-point was -2.7 (range 2 to -10) compared to -9.5 (range -8 to -12) postoperatively (p <0.003). No prolapse recurrence was noted. Mean operative time, blood loss and postoperative hospital stay were 238 minutes (range 160 to 300), 129 ml (range 20 to 900) and 3 days (range 1 to 6), respectively. Functional outcome improvement was statistically significant for total UDI-6-6 to 3 (p = 0.04), quality of life-4.1 to 2.1 (p <0.27) and IIQ-7-6 to 2 (p = 0.3), respectively. CONCLUSIONS: Peritoneocolpopexy performed reliably to correct symptomatic pelvic organ prolapse with satisfactory anatomical outcomes for apical support. Longer term followup is required to fully assess durability of repair.

Management of complications of mesh surgery.

PURPOSE OF REVIEW: Transvaginal placements of synthetic mid-urethral slings and vaginal meshes have largely superseded traditional tissue repairs in the current era because of presumed efficacy and ease of implant with device 'kits'. The use of synthetic material has generated novel complications including mesh extrusion, pelvic and vaginal pain and mesh contraction. In this review, our aim is to discuss the management, surgical techniques and outcomes associated with mesh removal. RECENT FINDINGS: Recent publications have seen an increase in presentation of these mesh-related complications, and reports from multiple tertiary centers have suggested that not all patients benefit from surgical intervention. SUMMARY: Although the true incidence of mesh complications is unknown, recent publications can serve to guide physicians and inform patients of the surgical outcomes from mesh-related complications. In addition, the literature highlights the growing need for a registry to account for a more accurate reporting of these events and to counsel patients on the risk and benefits before proceeding with mesh surgeries.

Optically transparent and environmentally durable superhydrophobic coating based on functionalized SiO2 nanoparticles.

Optical surfaces such as mirrors and windows that are exposed to outdoor environmental conditions are susceptible to dust buildup and water condensation. The application of transparent superhydrophobic coatings on optical surfaces can improve outdoor performance via a 'self-cleaning' effect similar to the Lotus effect. The contact angle (CA) of water droplets on a typical hydrophobic flat surface varies from 100° to 120°. Adding roughness or microtexture to a hydrophobic surface leads to an enhancement of hydrophobicity and the CA can be increased to a value in the range of 160°-175°. This result is remarkable because such behavior cannot be explained using surface chemistry alone. When surface features are on the order of 100 nm or smaller, they exhibit superhydrophobic behavior and maintain their optical transparency. In this work we discuss our results on transparent superhydrophobic coatings that can be applied across large surface areas. We have used functionalized silica nanoparticles to coat various optical elements and have measured the CA and optical transmission between 190 and 1100 nm on these elements. The functionalized silica nanoparticles were dissolved in a solution of the solvents, while the binder used was a polyurethane clearcoat. This solution was spin-coated onto a variety of test glass substrates, and following a curing period of about 30 min, these coatings exhibited superhydrophobic behavior with a static CA ≥ 160°.

Long-term outcomes of autologous pubovaginal fascia slings: is there a difference between primary and secondary slings?

INTRODUCTION: To report our long-term pubovaginal slings (PVS) outcomes between primary (PVS1) and secondary (PVS2) autologous fascia PVS, with the hypothesis that outcomes in PVS1 will be better than in PVS2. MATERIALS AND METHODS: IRB approved retrospective study of women undergoing PVS between 1996 and 2011 with minimum 6 months follow-up. Data reviewed included demographics, questionnaires that is, UDI-6, IIQ-7, QOL, prior anti-incontinence procedure, associated repairs, urodynamic findings and repeat procedures. Primary outcome and surgical success defined by: (1) QOL ≤ 3, (2) UDI question 3 on SUI ≤ 1, and (3) no SUI re-treatment/operation. Secondary outcomes included all other patient reported outcome measures (PROM). RESULTS: Of 110 patients, 84 had follow-up. Mean age was 61 years (38-88) and median follow-up was 89 months (7-189). Demographic findings and type of fascia used were similar between the two groups. Mean postoperative scores were not statistically significant for total UDI-6 score (P = 0.62), IIQ-7 (P = 0.30) and QOL (P = 0.35) between groups, but was statistically significant compared to baseline (P = 0.001) as expected. Twelve patients, 3 in PVS1 and 9 in PVS2 underwent subsequent procedures. Surgical success rate was 76% in PVS1 and 52% in PVS2 for those with completed questionnaires. Overall, 78% (28) in PVS1 and 69% (33) in PVS 2 required no further surgical intervention at last follow-up. CONCLUSION: At long-term follow-up of average 7.4 years, primary and secondary PVS patients had comparable favourable functional outcomes with low morbidity. However, secondary PVS patients had lower success rates as per our definition with higher rate of additional procedures.

Which way up? Recognition of homologous DNA segments in parallel and antiparallel alignments.

Homologous gene shuffling between DNA molecules promotes genetic diversity and is an important pathway for DNA repair. For this to occur, homologous genes need to find and recognize each other. However, despite its central role in homologous recombination, the mechanism of homology recognition has remained an unsolved puzzle of molecular biology. While specific proteins are known to play a role at later stages of recombination, an initial coarse grained recognition step has, however, been proposed. This relies on the sequence dependence of the DNA structural parameters, such as twist and rise, mediated by intermolecular interactions, in particular, electrostatic ones. In this proposed mechanism, sequences that have the same base pair text, or are homologous, have lower interaction energy than those sequences with uncorrelated base pair texts. The difference between the two energies is termed the "recognition energy." Here, we probe how the recognition energy changes when one DNA fragment slides past another, and consider, for the first time, homologous sequences in antiparallel alignment. This dependence on sliding is termed the "recognition well." We find there is a recognition well for anti-parallel, homologous DNA tracts, but only a very shallow one, so that their interaction will differ little from the interaction between two nonhomologous tracts. This fact may be utilized in single molecule experiments specially targeted to test the theory. As well as this, we test previous theoretical approximations in calculating the recognition well for parallel molecules against MC simulations and consider more rigorously the optimization of the orientations of the fragments about their long axes upon calculating these recognition energies. The more rigorous treatment affects the recognition energy a little, when the molecules are considered rigid. When torsional flexibility of the DNA molecules is introduced, we find excellent agreement between the analytical approximation and simulations.

Long-term functional outcomes following nonradiated vesicovaginal repair.

PURPOSE: We investigated the long-term impact on bladder and sexual symptoms in women with prior vesicovaginal fistula repair, particularly those previously treated before referral. MATERIALS AND METHODS: After receiving institutional review board approval we reviewed the charts of women who underwent nonradiated vesicovaginal fistula repair for demographics, surgical approach (vaginal or abdominal) and functional outcomes with a minimum 6-month followup. Patients lost to followup were reached by a structured phone interview and/or mailed validated lower urinary tract questionnaires, including the UDI-6 (Urogenital Distress Inventory-6), IIQ-7 (Incontinence Impact Questionnaire-7) and FSFI (Female Sexual Function Index). Three surgical groups were compared, including naïve-no prior repair, recurrent-1 prior repair and other-more than 2 repairs with the hypothesis of worse outcomes with more repairs. RESULTS: From 1996 to 2011 vesicovaginal fistula repair was performed in 66 patients, including in 42 as primary treatment (vaginal vs abdominal approach in 31 vs 11), in 14 as secondary treatment, and in 10 who underwent more than 2 repairs. Mean patient age was 45 years (range 24 to 87), mean body mass index was 29 kg/m(2) (range 19 to 43) and mean followup was 55 months (range 6 to 198). The overall repair success rate was 97%. There was no difference in functional outcomes in questionnaire responders among the 3 groups for lower urinary tract symptoms (62% on UDI-6/IIQ-7). However, for FSFI (33% of patients) there was female sexual dysfunction in patients who underwent transabdominal repair and in women with 2 repairs. CONCLUSIONS: Long-term followup of patients with vesicovaginal fistula repair indicated no differences in lower urinary tract outcomes at a mean 7-year followup between primary and recurrent repairs. There was a difference in sexual function, although it was not statistically significant. Sexual activity among responders was low.

Overcoming the challenges of characterizing normal urodynamic parameters in middle-aged and older women.

INTRODUCTION: To describe urodynamic study (UDS) findings in middle-aged and older women with various lower urinary tract symptoms (LUTS) who were found to have a normal study interpretation. MATERIALS AND METHODS: Following institutional review board approval, UDS tracings of non-neurogenic women who were tested for various LUTS and whose study was interpreted as normal were reviewed. Demographic data, indications for UDS, and UDS parameter findings were extracted. UDS was conducted according to an established protocol using a 6F dual-lumen catheter (ICS guidelines) with a Laborie system and interpreted with a pre-existing template to standardize each reading. The fill-void study was frequently repeated during the same UDS session to confirm normal findings. Study interpretation was done by a neutral reviewer with UDS expertise. RESULTS: From 2000-2012, 42 middle-aged women, who had been coded as having a normal study, were retrospectively reviewed from a database of over 2200 studies. The majority were Caucasian, with mean age 63 (range 42-85), mean body mass index 24.5 (20-37), mean parity 2 (0-4), and 67% were post-menopausal. Of the 42 patients, 28 underwent a second fill-void study. UDS findings were reported based on clinical indication for UDS: 1) incontinence, 2) pelvic organ prolapse, or 3) other LUTS symptoms. UDS findings were consistent between first and second studies. CONCLUSIONS: UDS parameters from a cohort of middle-aged and older women with normal findings could serve as reference values when interpreting urodynamic studies or for designing an age-comparable nomogram.

A surprisingly low prevalence of demonstrable stress urinary incontinence and pelvic organ prolapse in women with multiple sclerosis followed at a tertiary neurogenic bladder clinic.

PURPOSE: We report the prevalence of stress urinary incontinence and pelvic organ prolapse in patients with multiple sclerosis referred to a tertiary care neurogenic bladder clinic. MATERIALS AND METHODS: We queried an institutional review board approved neurogenic bladder database for urodynamic and demographic data on patients with multiple sclerosis followed for lower urinary tract symptoms in a 12-year period. Demographic information included multiple sclerosis classification, age at initial visit, body mass index, parity and pelvic examination findings. Prolapse was defined as stage 2 prolapse or greater. Stress urinary incontinence was defined as urodynamic stress incontinence and/or incontinence on a supine stress test. RESULTS: Included in analysis were 280 women with a mean age of 50 years and a mean 13-year history of multiple sclerosis. Relapse remitting multiple sclerosis was noted in 40% of patients, while 45 (16%) had stress urinary incontinence. Women with stress urinary incontinence had a higher average maximum urine flow (14 vs 9 ml per second, p <0.003), higher voided volume (272 vs 194 cc, p = 0.018) and higher body mass index (30 vs 25 kg/m(2), p <0.005). Overall, 23 women (9%) had pelvic organ prolapse, including 2 (9%) with posterior prolapse only, 8 (35%) with anterior prolapse only and 13 (56%) with posterior and anterior prolapse. There was no difference in age, body mass index or multiple sclerosis subtype between women with vs without pelvic organ prolapse. CONCLUSIONS: The 14% prevalence of demonstrable stress urinary incontinence and 9% rate of pelvic organ prolapse are markedly lower than published historical data on an age matched cohort without multiple sclerosis. The surprisingly low prevalence of stress urinary incontinence and pelvic organ prolapse in women with multiple sclerosis may be attributable to decreased activity, a neurogenically enhanced vesicourethral unit or other functional or anatomical etiologies.

Intermediate outcomes after transcorporal placement of an artificial urinary sphincter.

OBJECTIVES: To report the intermediate outcomes of a transcorporally placed artificial urinary sphincter. METHODS: Medical records of 16 consecutive patients treated with transcorporal placement of artificial urinary sphincter from March 2003 to October 2008 were reviewed. The indications for surgery, operative logs, postoperative evaluations, complication rate and postoperative questionnaire assessment utilizing the International Continence Society short form for men were analyzed. RESULTS: Eight patients each underwent primary transcorporal cuff placement and revision surgery. Complete data for analysis were available in 15 patients at a median follow up of 45 months (range 23-91 months). The success rate (defined as use of 0-1 pads per day) was 80% (12/15 patients). Average voiding score was 2/20 (standard deviation 1.88), average irritative score was 3/24 (standard deviation 4.92) and the mean Quality-of-Life score was 0.66 (standard deviation 1.04). CONCLUSIONS: Transcorporal placement of an artificial urinary sphincter is both safe and efficacious in patients with a small caliber or atrophic urethra, either as a primary or salvage procedure. Efficacy and level of satisfaction in this subset of patients is equivalent to those undergoing traditional artificial urinary sphincter cuff placement.

Antibody-Oligonucleotide Conjugation Using a SPAAC Copper-Free Method Compatible with 10× Genomics' Single-Cell RNA-Seq.

Recent advances in multimodal approaches toward single-cell analyses present valuable data points that can complement standard flow cytometry data. In particular, the overlay of cell-surface proteome data with gene expression analysis presents a necessary advancement, particularly in the field of immunology. Here we describe a copper-free click chemistry method for the generation of antibody-oligonucleotide complexes and present the steps for its employment in the context of the 10× genomics droplet-based single-cell RNA-seq workflow, providing a method for coupling proteomic and transcriptomic analyses in an efficient and cost-effect manner.