Rehabilitation of People With Chronic Spinal Cord Injury Using a Laparoscopically Implanted Neurostimulator: Impact on Mobility and Urinary, Anorectal, and Sexual Functions.

OBJECTIVES: This study aimed to assess the impact of the laparoscopic implantation of neuromodulation electrodes (Possover-LION procedure) on mobility and on sexual, urinary, and anorectal functions of people with chronic spinal cord injury (SCI). MATERIAL AND METHODS: Longitudinal analysis of 30 patients with chronic SCI (21 ASIA impairment scale (AIS) A, eight AIS B, and one AIS C) submitted to the Possover-LION procedure for bilateral neuromodulation of femoral, sciatic, and pudendal nerves. Assessments were performed before the surgical procedure and at 3, 6, and 12 months postoperatively. The primary outcome was evolution in walking, measured by the Walking Index for Spinal Cord Injury score, preoperatively and at 12 months. Secondary outcomes were changes in overall mobility (Mobility Assessment Tool for Evaluation of Rehabilitation score), urinary function and quality of life (Qualiveen questionnaire), and bowel (time for bowel emptying proceedings and Wexner's Fecal Incontinence Severity Index [FISI]) and sexual functions (International Index of Erectile Function for men and Female Sexual Function Index for women). Surgical time, intraoperative bleeding, and perioperative complications were also recorded. RESULTS: Qualitatively, 18 of 25 (72%) patients with thoracic injury and 3 of 5 (60%) patients with cervical injury managed to establish a walker-assisted gait at one-year follow-up (p < 0.0001). A total of 11 (47.8%) have improved in their urinary incontinence (p < 0.0001), and seven (30.4%) improved their enuresis (p = 0.0156). The FISI improved from a median of 9 points preoperatively to 5.5 at 12 months (p = 0.0056). Of note, 20 of 28 (71.4%) patients reported an improvement on genital sensitivity at 12 months postoperatively (p < 0.0001), but this was not reflected in sexual quality-of-life questionnaires. CONCLUSIONS: Patients experienced improved mobility and genital sensitivity and a reduction in the number of urinary and fecal incontinence episodes. By demonstrating reproducible outcomes and safety, this study helps establish the Possover-LION procedure as an addition to the therapeutic armamentarium for the rehabilitation of patients with chronic SCI. CLINICAL TRIAL REGISTRATION: This study was registered at the WHO Clinical Trials Database through the Brazilian Registry of Clinical Trials-REBEC (Universal Tracking Number: U1111-1261-4428).

CO2 Laser and radiofrequency compared to a sham control group in treatment of stress urinary incontinence (LARF study arm 3). A randomized controlled trial.

INTRODUCTION AND HYPOTHESIS: Female stress urinary incontinence (SUI) is a prevalent condition, and conservative treatment options are needed. Were evaluated CO2 laser and radiofrequency as treatment for SUI. METHODS: One hundred thirty-nine women with SUI were eligible and randomized in a three-arm double-blind randomized controlled trial into radiofrequency (RF), laser (LS) and sham control (SCT) groups, with 3-monthly outpatient treatment sessions. One hundred fourteen women were included, 38 in each group, during a 12-month follow-up. The primary outcomes were: subjective improvement of SUI, evaluated on a Likert scale, and objective cure, which was a composite outcome defined according to negative stress tests, voiding diary and pad test. Questionnaires were also applied. The sample size was calculated to provide 80% power to identify a 20% difference between groups, p < 0.05. RESULTS: Subjective improvement and objective cure of SUI were identified respectively in 72.6% and 45.2% in LS and in 61.7% and 44.7% in RF, both significantly higher than the 30.0% and 14.0% in SCT. Considering only mild cases (pad test < 10 g), objective cure was achieved in 66.7% in LS, 63.6% in RF and 22.2% in SCT. Significant reduction in the number of episodes of urinary incontinence was found according to voiding diaries (p = 0.029) and pad weight (p = 0.021). A significant reduction in urgency and urinary loss during sexual intercourse was observed only with LS and RF. Improvement in quality of life was also verified by the I-QoL and ICIQ-SF in favor of the energy-treated groups. CONCLUSIONS: CO2 laser and radiofrequency are outpatient options for SUI treatment, with no major complications. They had similar results and presented better results than in the sham control group.

Treatment for vaginal agenesis: A prospective and comparative study between vaginal dilation and surgical neovaginoplasty.

OBJECTIVE: To compare, in terms of anatomical, functional, and sexual aspects, two types of treatment for women with vaginal agenesis: progressive dilation or surgical neovaginoplasty. METHODS: Women with vaginal agenesis underwent either dilation treatment using the Frank method or surgical treatment using the modified Abbé-McIndoe technique with oxidized cellulose. Patients were evaluated 3-6 months after treatment for a follow-up including medical history, physical examination, general satisfaction, clinical aspect of the vagina, Female Sexual Function Index, and three-dimensional pelvic floor ultrasound. RESULTS: In total, 20 women with vaginal agenesis were included in the present study; nine in the dilation group and 11 in the surgical group. A comparison between the groups (vaginal dilation and surgical neovaginoplasty) showed efficacy in neovagina formation after both treatments, with a statistically significant difference between the pre- and post-treatment periods (P value pre- × post-dilation group <0.0001 and P value pre- × post-surgical group <0.0001). There were no statistical differences in total vaginal length measurements (P value post-dilation × post-surgical = 0.09) or Female Sexual Function Index scores (P = 0.72) after both treatments. CONCLUSION: Both treatments had satisfactory efficacy and positive outcomes for patients with vaginal agenesis concerning anatomical, functional, and sexual aspects, with minimum complications in the surgical group. Dilation treatment can remain the first-line therapy.

A Single Dose of a Hybrid hAdV5-Based Anti-COVID-19 Vaccine Induces a Long-Lasting Immune Response and Broad Coverage against VOC.

Most approved vaccines against COVID-19 have to be administered in a prime/boost regimen. We engineered a novel vaccine based on a chimeric human adenovirus 5 (hAdV5) vector. The vaccine (named CoroVaxG.3) is based on three pillars: (i) high expression of Spike to enhance its immunodominance by using a potent promoter and an mRNA stabilizer; (ii) enhanced infection of muscle and dendritic cells by replacing the fiber knob domain of hAdV5 by hAdV3; (iii) use of Spike stabilized in a prefusion conformation. The transduction with CoroVaxG.3-expressing Spike (D614G) dramatically enhanced the Spike expression in human muscle cells, monocytes and dendritic cells compared to CoroVaxG.5 that expressed the native fiber knob domain. A single dose of CoroVaxG.3 induced a potent humoral immunity with a balanced Th1/Th2 ratio and potent T-cell immunity, both lasting for at least 5 months. Sera from CoroVaxG.3-vaccinated mice was able to neutralize pseudoviruses expressing B.1 (wild type D614G), B.1.117 (alpha), P.1 (gamma) and B.1.617.2 (delta) Spikes, as well as an authentic P.1 SARS-CoV-2 isolate. Neutralizing antibodies did not wane even after 5 months, making this kind of vaccine a likely candidate to enter clinical trials.

Lumbosacral plexus MR tractography: A novel diagnostic tool for extraspinal sciatica and pudendal neuralgia?

BACKGROUND: Diagnosing extraspinal sciatica and pudendal neuralgia remains a clinical challenge. MRI and MR Neurography (MRN) are currently the standard techniques used to support the diagnosis of extraspinal lumbosacral plexus entrapments; however, for the intrapelvic portions of the lumbosacral plexus their accuracy is still limited. MR Tractography (MRT) feasibility to image the lumbosacral plexus has been demosntrated, but its clinical applications have yet to be determined. PURPOSE: To correlate MRT with intraoperative findings in patients undergoing laparoscopic treatment of intrapelvic entrapments of the lumbosacral plexus and compare its accuracy with Neuropelveological clinical assessment and MRN. MATERIALS AND METHODS: This is a retrospective analysis of MRT reconstructions of diffusion tensor imaging (DTI) sequences acquired for the MRN collected from a cohort of 13 patients undergoing laparoscopic detrapment of the lumbosacral plexus. The primary outcome of this study was the correlation of MRT reconstruction with intraoperative findings. Secondary outcomes included the correlation of MRN, preoperative Neuropelveological clinical diagnoses and the diffusion-weighted imaging (DWI) fractional anisotropy (FA) and Apparent Diffusion Coefficient (ADC) in patients undergoing pelvic MRI and MRN for the investigation of intrapelvic nerve entrapments. RESULTS: MRT correlated with intraoperative findings in 11 of 13 patients (85%). Neuropelveological clinical assessment was able to accurately diagnose a pelvic nerve entrapment in 12/13 patients (92%) and MRN agreed with surgical findings in only 2/13 (15%) patients. MRT was significantly superior to MRN (p < 0.001). FA and ADC did not correlate with the identification of a nerve entrapment, likely due to limitations regarding the placement of the seedpoints. CONCLUSIONS: This initial, retrospective analysis, suggests that MRT is superior to MRN at diagnosing intrapelvic entrapments of the lumbosacral plexus. A prospective, double-blinded study is underway to validate this data, but these initial findings show great potential for MRT as a diagnostic tool for extraspinal sciatica and pudendal neuralgia. Clinical Trials Registry: U1111-1261-4910 (REBEC - Brazilian Registry for Clinical Trials).

Progesterone's role in deep infiltrating endometriosis: Progesterone receptor and estrogen metabolism enzymes expression and physiological changes in primary endometrial stromal cell culture.

To study progesterone signaling activation, we measured changes in extracellular pH as a reflection of Na+/H+ exchange (NHE) using a cytosensor microphysiometer and assessed progesterone receptor (PR) and estrogen metabolism enzymes mRNA expression in cultured endometrial cells from women with deep infiltrating endometriosis and healthy controls using real-time quantitative PCR. This study was conducted at a University hospital and included patients with and without deep infiltrating endometriosis (DIE). Primary endometrial stromal cells (ECs) from women with DIE and controls were treated with 17ß-estradiol and progesterone prior to microphysiometer measurements and qPCR evaluations. Decreased progesterone responsiveness and decreased total nuclear PR and HSD17B1 mRNA expression were observed in cultured ECs from women with deep infiltrating endometriosis relative to those from control samples before and after hormone treatment. These cells also showed increased 17ß-hydroxysteroid dehydrogenases types 2 (HSD17B2) relative to control group and increased expression of aromatase (CYP19) after exposure to progesterone. These physiological and expression patterns observed in ECs cultures from women with DIE reinforces previous findings in the literature supporting the progesterone resistance hypothesis in the pathogenesis of endometriosis.

Superior gluteal vein syndrome: an intrapelvic cause of sciatica.

The role of malformed or dilated branches of iliac vessels in causing pelvic pain is not well understood. Such vessels may entrap nerves of the lumbosacral (LS) plexus against the pelvic sidewalls, producing symptoms not typically encountered in gynecological practice, including sciatica and refractory urinary and/or anorectal dysfunction. We describe cases of sciatica in which laparoscopy revealed compression of the LS plexus by variant superior gluteal veins (SGVs). In demonstrating an improvement in patient symptoms after decompression, we identify this neurovascular conflict as a potential intrapelvic cause of sciatica. This study is a retrospective case series (Canadian Task Force Classification II-3). Nerve decompression laparoscopies were performed in São Paulo, Brazil. Thirteen female patients undergoing laparoscopy for sciatica with no clear spinal or musculoskeletal causes were included in this study. In all cases, we identified LS entrapment by aberrant SGVs, and performed decompression by vessel ligation. The average preoperative visual analog scale score of 9.62 ± 0.77 decreased significantly to 2.54 ± 2.88 post-operatively (P < 0.001). The success rate (defined as ≥ 50% improvement in visual analog scale score) was 92.3%, over a follow-up of 13.2 ± 10.6 months. Our case series demonstrates a high success rate and significant decrease in pain scores after laparoscopic intrapelvic decompression, thereby identifying pelvic nerve entrapment by aberrant SGVs as a potential yet previously unrecognized cause of sciatica. This intrapelvic neurovascular conflict-the SGV syndrome-should be considered in cases of sciatica with no identifiable spinal or musculoskeletal etiology.

Pelvic floor muscle training is better than hypopressive exercises in pelvic organ prolapse treatment: An assessor-blinded randomized controlled trial.

AIMS: To verify if hypopressive exercises (HEs) can improve pelvic organ prolapse (POP) symptoms equally or better than pelvic floor muscle training (PFMT). METHODS: Randomized controlled trial. Symptomatic women with untreated stage II POP according to the Pelvic Organ Prolapse Quantification System (POP-Q) having the ability to contract their pelvic floor muscles were invited. The outcome measures were POP symptoms as measured by specific questions and Prolapse Quality of Life (P-QoL); POP severity as measured by POP-Q; and PFM function. Intervention consisted by 12 weeks of PFMT or an HE home exercise program with bimonthly sessions with a physiotherapist. The protocol consisted of three initial sessions to learn how to perform the exercises correctly, followed by 3 months of exercise with monthly progression. Volunteers filled out exercise diaries to record their compliance. RESULTS: PFMT presented better results in terms of the following symptoms: a bulge/lump from or in the vagina, heaviness or dragging on the lower abdomen, and stress incontinence. PFMT also presented better results regarding the Prolapse impact and role, social and personal limitations of P-QoL. Regarding the total number of symptoms at the end, the PFMT group presented a mean of 1.7 (±1.2), and the HE group presented a mean of 2.8 (±1,1); the effect size was 1.01 in favor of the PFMT group (95%CI = 1.002-1.021). CONCLUSION: Both groups exhibited improvements in POP symptoms, quality of life, prolapse severity, and PFM function. PFMT was superior to HE for all outcomes.

Laparoscopic implantation of electrodes for bilateral neuromodulation of the pudendal nerves and S3 nerve roots for treating pelvic pain and voiding dysfunction.

INTRODUCTION AND HYPOTHESIS: The objective of this video is to describe the technique for laparoscopic implantation of electrodes for bilateral neuromodulation of S3 and pudendal nerves. We report a successful case of a 48-year-old woman with spina bifida occulta referred with a 14-year history of intense acyclic pelvic pain, urinary hesitancy, and intermittent flow refractory to various conservative measures. METHODS: The procedure began with the removal of two previously placed InterStims. A quadripolar electrode was then laparoscopically inserted into Alcock's canal and attached to the pelvic pectineal line. Another lead was placed juxtaneurally to S3. Lead contacts were then exteriorized, and the peritoneum closed. The same procedure was then performed on the contralateral side. The leads were connected to a 16-pole rechargeable pulse generator. Postoperatively, the patient developed an acute dissection and partial thrombosis of the external iliac artery, which was treated endovascularly. RESULTS: Complete pain resolution was observed with simultaneous S3 and pudendal stimulation, with pudendal stimulation turned off for voiding. CONCLUSIONS: We conclude that laparoscopic implantation of neuromodulation electrodes allows simultaneous stimulation of S3 and pudendal nerves, providing more programming options and possibly increasing success rates in complex pelvic floor dysfunction cases.

Female double incontinence: prevalence, incidence, and risk factors from the SABE (Health, Wellbeing and Aging) study.

INTRODUCTION AND HYPOTHESIS: Double Incontinence (DI) is incontinence of urine and stool and is an extreme manifestation of pelvic floor dysfunction. The objective of this study was to estimate the prevalence and incidence of DI and the risk factors in elderly women in São Paulo, Brazil. METHODS: This was a prospective study in women aged 65 years or older evaluated in 2006 and re-evaluated in 2010. The sample was selected by two-phase stratified sampling with replacement and probability proportional to size. The likelihood ratio test was performed and Cox regression curves were generated to evaluate the equality of survival. Poisson's regression was used to evaluate risk factors. RESULTS: This is the first study on the incidence of DI in elderly women. A total of 864 elderly women were interviewed in 2006. The prevalence rate of DI was 4.9%. The incidence rate of DI in the period between 2006 and 2010 was 13.8/1,000 person-years. Associated factors were the presence of chronic obstructive pulmonary disease, hypertension, difficulty with basic activities of daily living (BADL) and instrumental activities of daily living (IADL), polypharmacy and falls in the last year. Poisson's regression analysis showed that falls in the last year and difficulty with at least three IADL were risk factors for DI. CONCLUSIONS: The incidence of DI seems to be high in this population. Falls in the last year and difficulty with at least three IADL were identified as risk factors. Preventive measures must be implemented with public health policies to prevent increases in DI.

Pelvic Floor 3D Ultrasound of Women with a TVT, TVT-O, or TVT-S for Stress Urinary Incontinence at the Three-year Follow-up / Ultrassonografia tridimensional do assoalho pélvico após 3 anos de correção cirúrgica de incontinência urinária de esforço por sling retropúbico, transobturador, ou de incisão única

Abstract Objective Using three-dimensional ultrasound (3D-US), we aimed to compare the tape position and the angle formed by the sling arms in different techniques of midurethral sling insertion for the surgical treatment of stress urinary incontinence, three years after surgery. In addition, we examined the correlations between the US findings and the clinical late postoperative results. Methods A prospective cross-sectional cohort study of 170 patients who underwent a sling procedure between May 2009 and December 2011 was performed. The final sample, with US images of sufficient quality, included 26 retropubic slings (tension-free vaginal tape, TVT), 42 transobturator slings (tension-free vaginal tape-obturator, TVTO), and 37 single-incision slings (tension-free vaginal tape-Secur, TVT-S). The images (at rest, during the Valsalva maneuver, and during pelvic floor contraction) were analyzed offline by 2 different observers blinded against the surgical and urinary continence status. Group comparisons were performed using the Student t-test, the chi-squared and the Kruskal-Wallis tests, and analyses of variance with Tukey multiple comparisons. Results Differences among the groups were found in themean angle of the tape arms (TVT = 119.94°, TVT-O = 141.93°, TVT-S = 121.06°; p < 0.001) and in the distance between the bladder neck and the tape at rest (TVT = 1.65 cm, TVT-O = 1.93 cm, TVTS = 1.95 cm; p = 0.010). The global objective cure rate was of 87.8% (TVT = 88.5%, TVT-O = 90.5%, TVT-S = 83.8%; p = 0.701). The overall subjective cure rate was of 83.8% (TVT = 88.5%, TVT-O = 88.5% and TVT-S = 78.4%; p = 0.514). The slings were located in the mid-urethra in 85.7% of the patients (TVT = 100%, TVT-O = 73.8%, TVTS = 89.2%; p = 0.001), with a more distal location associated with obesity (distal: 66.7% obese; mid-urethra: 34% obese; p = 0.003). Urgency-related symptoms were observed in 23.8% of the patients (TVT = 30.8%, TVT-O = 21.4%, TVT-S = 21.6%; p = 0.630). Conclusions The angle formed by the arms of the sling tape was more obtuse for the transobturator slings compared with the angles for the retropubic or single-incision slings. Retropubic slings were more frequently located in the mid-urethra compared with the other slings, regardless of obesity. However, the analyzed sonographic measures did not correlate with the urinary symptoms three years after the surgery.

Resumo Objetivo Comparar por meio de ultrassom tridimensional (US-3D) a posição e o ângulo entre os braços da faixa, em diferentes técnicas de inserção de sling de uretra média, para tratamento de incontinência urinária de esforço, 3 anos após a cirurgia, correlacionando os achados ultrassonográficos aos resultados clínicos pós-operatórios. Métodos Este é umestudo de coorte transversal prospectivo de 170 pacientes que se submeteram a um procedimento de sling entremaio de 2009 e dezembro de 2011. Foi possível avaliar as imagens de US em 105 pacientes: 26 com tension-free vaginal tape (TVT), 42 com tension-free vaginal tape-obturator (TVT-O) e 37 com tension-free vaginal tape-Secur (TVT-S). As imagens (em repouso, em manobra de Valsalva e em contração perineal) foram analisadas por dois observadores diferentes, que desconheciam o tipo de sling utilizado na cirurgia, assimcomo as queixas da paciente. A análise estatística foi realizada por meio dos testes t de Student, qui-quadrado, Kruskal-Wallis, e análise de variância com comparações múltiplas de Tukey. Resultados As médias dos ângulos entre os braços da faixa foram: TVT = 119,94°, TVT-O = 141,93°, TVT-S = 121,06° (p < 0,001). As médias das distâncias entre o colo vesical e a faixa, em repouso, foram: TVT = 1,65 cm, TVT-O = 1,93 cm, TVTS = 1,95 cm (p = 0,010). A taxa de cura objetiva dos slings foi de 87,8% (TVT = 88,5%, TVT-O = 90,5% e TVT-S = 83,8%; p = 0,701). A taxa de cura subjetiva foi de 83,8% (TVT = 88,5%, TVT-O = 88,5% e TVT-S = 78,4%; p = 0,514). Os slings estavam na uretra média em 85,7% (TVT = 100%, TVT-O = 73,8% e TVT-S = 89,2%; p = 0,001) dos pacientes, e a localização mais distal foi associada a obesidade (distal: 66,7% obesas; uretra média: 34% obesas; p = 0.003). Os sintomas de urgência foram observados em 23,8% das pacientes (TVT = 30,8%, TVT-O = 21,4%, TVT-S = 21,6%; p = 0,630). Não houve diferenças significativas quando se comparam os achados ultrassonográficos e os grupos de pacientes com sintomas de urgência, cura subjetiva e objetiva. Conclusão O ângulo formado pelos braços da faixa foi mais obtuso noTVT-Oquando comparado com o TVT ou o TVT-S. Os TVTs foram localizados mais frequentemente na uretra média quando comparados com os outros dois grupos, mesmo em pacientes obesas. Entretanto, as medidas ultrassonográficas não tiveram correlação com os sintomas urinários três anos após a cirurgia.

Hysteropreservation versus hysterectomy in the surgical treatment of uterine prolapse: systematic review and meta-analysis.

INTRODUCTION AND HYPOTHESIS: The efficacy and safety of removing or preserving the uterus during reconstructive pelvic surgery is a matter of debate. METHODS: We performed a systematic review and meta-analysis of studies that compared hysteropreservation and hysterectomy in the management of uterine prolapse. PubMed, Medline, SciELO and LILACS databases were searched from inception until January 2017. We selected only randomized controlled trials and observational cohort prospective comparative studies. Primary outcomes were recurrence and reoperation rates. Secondary outcomes were: operative time, blood loss, visceral injury, voiding dysfunction, duration of catheterization, length of hospital stay, mesh exposure, dyspareunia, malignant neoplasia and quality of life. RESULTS: Eleven studies (six randomized and five non-randomized) were included involving 910 patients (462 in the hysteropreservation group and 448 in the hysterectomy group). Pooled data including all surgical techniques showed no difference between the groups regarding recurrence of uterine prolapse (RR 1.65, 95% CI 0.88-3.10; p = 0.12), but the risk of recurrence following hysterectomy was lower when the vaginal route was used with native tissue repair (RR 10.61; 95% CI 1.26-88.94; p = 0.03). Hysterectomy was associated with a lower reoperation rate for any prolapse compartment than hysteropreservation (RR 2.05; 95% CI 1.13-3.74; p = 0.02). Hysteropreservation was associated with a shorter operative time (mean difference -12.43 min; 95% CI -14.11 to -10.74 ; p < 0.00001) and less blood loss (mean difference -60.42 ml; 95% CI -71.31 to -49.53 ml; p < 0.00001). Other variables were similar between the groups. CONCLUSIONS: Overall, the rate of recurrence of uterine prolapse was not lower but the rate of reoperation for prolapse was lower following hysterectomy, while operative time was shorter and blood loss was less with hysteropreservation. The limitations of this analysis were the inclusion of nonrandomized studies and the variety of surgical techniques. The results should be interpreted with caution due to potential biases.

Pelvic Floor 3D Ultrasound of Women with a TVT, TVT-O, or TVT-S for Stress Urinary Incontinence at the Three-year Follow-up.

Objective Using three-dimensional ultrasound (3D-US), we aimed to compare the tape position and the angle formed by the sling arms in different techniques of mid-urethral sling insertion for the surgical treatment of stress urinary incontinence, three years after surgery. In addition, we examined the correlations between the US findings and the clinical late postoperative results. Methods A prospective cross-sectional cohort study of 170 patients who underwent a sling procedure between May 2009 and December 2011 was performed. The final sample, with US images of sufficient quality, included 26 retropubic slings (tension-free vaginal tape, TVT), 42 transobturator slings (tension-free vaginal tape-obturator, TVT-O), and 37 single-incision slings (tension-free vaginal tape-Secur, TVT-S). The images (at rest, during the Valsalva maneuver, and during pelvic floor contraction) were analyzed offline by 2 different observers blinded against the surgical and urinary continence status. Group comparisons were performed using the Student t-test, the chi-squared and the Kruskal-Wallis tests, and analyses of variance with Tukey multiple comparisons. Results Differences among the groups were found in the mean angle of the tape arms (TVT = 119.94°, TVT-O = 141.93°, TVT-S = 121.06°; p < 0.001) and in the distance between the bladder neck and the tape at rest (TVT = 1.65 cm, TVT-O = 1.93 cm, TVT-S = 1.95 cm; p = 0.010). The global objective cure rate was of 87.8% (TVT = 88.5%, TVT-O = 90.5%, TVT-S = 83.8%; p = 0.701). The overall subjective cure rate was of 83.8% (TVT = 88.5%, TVT-O = 88.5% and TVT-S = 78.4%; p = 0.514). The slings were located in the mid-urethra in 85.7% of the patients (TVT = 100%, TVT-O = 73.8%, TVT-S = 89.2%; p = 0.001), with a more distal location associated with obesity (distal: 66.7% obese; mid-urethra: 34% obese; p = 0.003). Urgency-related symptoms were observed in 23.8% of the patients (TVT = 30.8%, TVT-O = 21.4%, TVT-S = 21.6%; p = 0.630). Conclusions The angle formed by the arms of the sling tape was more obtuse for the transobturator slings compared with the angles for the retropubic or single-incision slings. Retropubic slings were more frequently located in the mid-urethra compared with the other slings, regardless of obesity. However, the analyzed sonographic measures did not correlate with the urinary symptoms three years after the surgery.

Objetivo Comparar por meio de ultrassom tridimensional (US-3D) a posição e o ângulo entre os braços da faixa, em diferentes técnicas de inserção de sling de uretra média, para tratamento de incontinência urinária de esforço, 3 anos após a cirurgia, correlacionando os achados ultrassonográficos aos resultados clínicos pós-operatórios. Métodos Este é um estudo de coorte transversal prospectivo de 170 pacientes que se submeteram a um procedimento de sling entre maio de 2009 e dezembro de 2011. Foi possível avaliar as imagens de US em 105 pacientes: 26 com tension-free vaginal tape (TVT), 42 com tension-free vaginal tape-obturator (TVT-O) e 37 com tension-free vaginal tape-Secur (TVT-S). As imagens (em repouso, em manobra de Valsalva e em contração perineal) foram analisadas por dois observadores diferentes, que desconheciam o tipo de sling utilizado na cirurgia, assim como as queixas da paciente. A análise estatística foi realizada por meio dos testes t de Student, qui-quadrado, Kruskal-Wallis, e análise de variância com comparações múltiplas de Tukey. Resultados As médias dos ângulos entre os braços da faixa foram: TVT = 119,94°, TVT-O = 141,93°, TVT-S = 121,06° (p < 0,001). As médias das distâncias entre o colo vesical e a faixa, em repouso, foram: TVT = 1,65 cm, TVT-O = 1,93 cm, TVT-S = 1,95 cm (p = 0,010). A taxa de cura objetiva dos slings foi de 87,8% (TVT = 88,5%, TVT-O = 90,5% e TVT-S = 83,8%; p = 0,701). A taxa de cura subjetiva foi de 83,8% (TVT = 88,5%, TVT-O = 88,5% e TVT-S = 78,4%; p = 0,514). Os slings estavam na uretra média em 85,7% (TVT = 100%, TVT-O = 73,8% e TVT-S = 89,2%; p = 0,001) dos pacientes, e a localização mais distal foi associada a obesidade (distal: 66,7% obesas; uretra média: 34% obesas; p = 0.003). Os sintomas de urgência foram observados em 23,8% das pacientes (TVT = 30,8%, TVT-O = 21,4%, TVT-S = 21,6%; p = 0,630). Não houve diferenças significativas quando se comparam os achados ultrassonográficos e os grupos de pacientes com sintomas de urgência, cura subjetiva e objetiva. Conclusão O ângulo formado pelos braços da faixa foi mais obtuso no TVT-O quando comparado com o TVT ou o TVT-S. Os TVTs foram localizados mais frequentemente na uretra média quando comparados com os outros dois grupos, mesmo em pacientes obesas. Entretanto, as medidas ultrassonográficas não tiveram correlação com os sintomas urinários três anos após a cirurgia.

Uterine Artery Embolization and Surgical Methods for the Treatment of Symptomatic Uterine Leiomyomas: A Systemic Review and Meta-analysis Followed by Indirect Treatment Comparison.

PURPOSE: There is significant discussion and uncertainty about the optimal management of symptomatic uterine leiomyomas (SULs). Nonsurgical procedures such as uterine artery embolization (UAE) have been developed. The goal of this study was to conduct a meta-analysis and an indirect treatment comparison to examine the comparative efficacy and safety of the surgical procedures to treat SULs compared with UAE. METHODS: MEDLINE, EMBASE, Lilacs, and the Cochrane Central Register of Controlled Trials databases were searched from inception to February 2016. Ten randomized controlled trials comparing UAE versus hysterectomy, myomectomy, and laparoscopic occlusion of the uterine arteries in patients with SUL published in a peer-reviewed journal were included. Two reviewers independently selected studies, assessed quality, and extracted data. Discrepancies were resolved through consensus. FINDINGS: Data from 986 patients submitted to UEA (n = 527) or surgery (n = 459) were analyzed. UAE had a lower risk of major complications (risk ratio [RR], 0.45 [95% CI, 0.22-0.95]; P = 0.04)and a higher risk of minor complications (RR, 1.65 [95% CI, 1.32-2.06]; P < 0.00001); UAE had a higher risk of re-intervention up to 2 years (RR, 3.74 [95% CI, 1.76-7.96]; P = 0.0006) and up to 5 years (RR, 5.01 [95% CI, 1.37-18.39]; P = 0.02); UAE had a similar risk of follicle-stimulating hormone levels >40 IU/L after 6 months (RR, 1.76 [95% CI, 0.24-12.95]; P = 0.58)and of recommending the procedure to another patient up to 5 years after treatment (RR, 1.00 [95% CI, 0.87-1.14]; P = 0.94). The indirect comparison between myomectomy and hysterectomy found that the 2 procedures were similar in the studied outcomes. IMPLICATIONS: Compared with surgery, UAE had lower rates of major complications with an increased risk of re-intervention up to 2 and 5 years after the first procedure. UAE compared with surgery had a similar risk of ovarian failure and similar recommendation of the procedure to another patient. However, the number of trials was limited, and there was a high risk of bias in at least 2 domains. None of the trials blinded the participants and personnel or the outcome assessment. PROSPERO identifier: CRD42015026319.

Plasma kallikrein enhances platelet aggregation response by subthreshold doses of ADP.

Human plasma kallikrein (huPK) potentiates platelet responses to subthreshold doses of ADP, although huPK itself, does not induce platelet aggregation. In the present investigation, we observe that huPK pretreatment of platelets potentiates ADP-induced platelet activation by prior proteolysis of the G-protein-coupled receptor PAR-1. The potentiation of ADP-induced platelet activation by huPK is mediated by the integrin αIIbß3 through interactions with the KGD/KGE sequence motif in huPK. Integrin αIIbß3 is a cofactor for huPK binding to platelets to support PAR-1 hydrolysis that contributes to activation of the ADP signaling pathway. This activation pathway leads to phosphorylation of Src, AktS473, ERK1/2, and p38 MAPK, and to Ca2+ release. The effect of huPK is blocked by specific antagonists of PAR-1 (SCH 19197) and αIIbß3 (abciximab) and by synthetic peptides comprising the KGD and KGE sequence motifs of huPK. Further, recombinant plasma kallikrein inhibitor, rBbKI, also blocks this entire mechanism. These results suggest a new function for huPK. Formation of plasma kallikrein lowers the threshold for ADP-induced platelet activation. The present observations are consistent with the notion that plasma kallikrein promotes vascular disease and thrombosis in the intravascular compartment and its inhibition may ameliorate cardiovascular disease and thrombosis.