Lung matrix and vascular remodeling in mechanically ventilated elastin haploinsufficient newborn mice.

Elastin plays a pivotal role in lung development. We therefore queried if elastin haploinsufficient newborn mice (Eln(+/-)) would exhibit abnormal lung structure and function related to modified extracellular matrix (ECM) composition. Because mechanical ventilation (MV) has been linked to dysregulated elastic fiber formation in the newborn lung, we also asked if elastin haploinsufficiency would accentuate lung growth arrest seen after prolonged MV of neonatal mice. We studied 5-day-old wild-type (Eln(+/+)) and Eln(+/-) littermates at baseline and after MV with air for 8-24 h. Lungs of unventilated Eln(+/-) mice contained ∼50% less elastin and ∼100% more collagen-1 and lysyl oxidase compared with Eln(+/+) pups. Eln(+/-) lungs contained fewer capillaries than Eln(+/+) lungs, without discernible differences in alveolar structure. In response to MV, lung tropoelastin and elastase activity increased in Eln(+/+) neonates, whereas tropoelastin decreased and elastase activity was unchanged in Eln(+/-) mice. Fibrillin-1 protein increased in lungs of both groups during MV, more in Eln(+/-) than in Eln(+/+) pups. In both groups, MV caused capillary loss, with larger and fewer alveoli compared with unventilated controls. Respiratory system elastance, which was less in unventilated Eln(+/-) compared with Eln(+/+) mice, was similar in both groups after MV. These results suggest that elastin haploinsufficiency adversely impacts pulmonary angiogenesis and that MV dysregulates elastic fiber integrity, with further loss of lung capillaries, lung growth arrest, and impaired respiratory function in both Eln(+/+) and Eln(+/-) mice. Paucity of lung capillaries in Eln(+/-) newborns might help explain subsequent development of pulmonary hypertension previously reported in adult Eln(+/-) mice.

Three-year outcomes of vaginal mesh for prolapse: a randomized controlled trial.

OBJECTIVE: To present the 3-year outcomes of a double-blind, multicenter, randomized trial comparing vaginal prolapse repair with and without mesh. METHODS: This was a planned final analysis of women with Pelvic Organ Prolapse Quantification (POP-Q) stage 2-4 prolapse randomized to traditional vaginal prolapse surgery without mesh and vaginal colpopexy repair with mesh. We evaluated anatomic, symptomatic, and combined cure rates for those with at least 3-year validated quality-of-life questionnaires and 2- or 3-year postoperative blinded POP-Q examination. Participants undergoing reoperation for recurrent prolapse were removed for anatomic and subjective outcomes analysis and considered failures for combined outcomes analysis. RESULTS: Sixty-five women were enrolled (33 mesh, 32 no mesh) before the study was prematurely halted as a result of a 15.6% mesh exposure rate. At 3 years, 51 of 65 (78%) had quality-of-life questionnaires (25 mesh, 26 no mesh) and 41 (63%) had examinations. Three participants died, three required reoperation for recurrent prolapse (all in mesh group), and eight were lost to follow-up. No differences were observed between groups at 3 years for prolapse stage or individual prolapse points. Stage improved for each group (90% and 86%) from baseline to 3 years (P<.01). Symptomatic improvement was observed with no differences in scores between groups. Cure rates did not differ between groups using a variety of definitions, and anatomic cure was lowest for the anterior compartment. CONCLUSION: There was no difference in 3-year cure rates when comparing patients undergoing traditional vaginal prolapse surgery without mesh with those undergoing vaginal colpopexy repair with mesh. CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov, www.clinicaltrials.gov, NCT00475540. LEVEL OF EVIDENCE: : I.

Vaginal dilators for prevention of dyspareunia after prolapse surgery: a randomized controlled trial.

OBJECTIVE: To compare rates of de novo dyspareunia in women with and without vaginal dilator use after posterior colporrhaphy. METHODS: This randomized controlled trial included sexually active patients with prolapse and no bothersome baseline dyspareunia undergoing posterior colporrhaphy. Patients were randomized to daily vaginal dilator use from postoperative weeks 4 through 8 or to no dilator use. Pelvic organ prolapse quantification examination and vaginal caliber were measured at baseline, 8 weeks, and 6 months postoperatively. Sexual function was evaluated at baseline, 3 months, and 6 months postoperatively using the Pelvic Organ Prolapse/Urinary Incontinence Sexual Function Questionnaire-12. Participants completed a Patient Global Impression of Improvement at 3 months and 6 months postoperatively. RESULTS: Sixty patients were randomized: 30 in the dilator group and 30 in the control group. There were no differences in baseline characteristics and postoperative vaginal caliber between groups. At 3 months, 9.5% of patients reported de novo dyspareunia in the dilator group compared with 19.2% of control patients (P=.44). At 6 months, 12.5% of patients in the dilator group reported de novo dyspareunia compared with 3.8% of control patients (P=.34). There was a 13% loss-to-follow-up rate, and therefore we did not meet appropriate power to detect a difference. There were no differences in overall sexual function or Patient Global Impression of Improvement scores between groups at 3 months and 6 months. CONCLUSION: There were no significant differences in de novo dyspareunia rates, overall postoperative sexual function scores, or global improvement scores between those using vaginal dilators compared with control patients.

The effect of uterine fibroid embolization on lower urinary tract symptoms.

INTRODUCTION AND HYPOTHESIS: The objective was to determine the effect of uterine fibroid embolization (UFE) on lower urinary tract symptoms (LUTS) and quality of life (QoL). METHODS: This prospective study included women with symptomatic fibroids and LUTS who underwent UFE between March 2008 and May 2010. Subjects underwent pre-procedural pelvic magnetic resonance imaging (MRI) and completed the Urogenital Distress Inventory (UDI-6), Incontinence Impact Questionnaire (IIQ-7), Prolapse and Incontinence Sexual Questionnaire (PISQ-12), Uterine Fibroid Symptom Quality of Life questionnaire (UFS-QoL), and a standardized 48-h bladder diary at baseline and 3 months after the procedure. Patient Global Impression of Improvement (PGI-I) assessed post-procedural patient satisfaction. The primary outcome was subjective improvement in LUTS at 3 months, as measured by a decrease in UDI-6 score. Univariate analysis, paired t test and a stepwise regression analysis were appropriately conducted. RESULTS: Fifty-seven patients underwent UFE and completed bladder diaries and questionnaires. At 3 months after UFE, patients reported a significant decrease in UDI-6, IIQ-7, and UFS-QoL, indicating an improvement in urinary symptoms and QoL. Bladder diaries showed a significant reduction in daytime and night-time voids. No difference was found in incontinence episodes. Uterine volume, dominant fibroid size, fibroid location, and MRI-confirmed bladder compression did not affect the difference in UDI-6 scores. In a stepwise regression model, BMI had a significant impact on the change in UDI-6 score, with a decrease of 1.18 points for each 1 unit increase in BMI. CONCLUSION: Uterine fibroid embolization significantly improves LUTS and urinary-related QoL. Obesity seems to attenuate this effect.

Inhibiting lung elastase activity enables lung growth in mechanically ventilated newborn mice.

RATIONALE: Mechanical ventilation with O2-rich gas (MV-O2) offers life-saving treatment for respiratory failure, but also promotes lung injury. We previously reported that MV-O2 of newborn mice increased lung elastase activity, causing elastin degradation and redistribution of elastic fibers from septal tips to alveolar walls. These changes were associated with transforming growth factor (TGF)-ß activation and increased apoptosis leading to defective alveolarization and lung growth arrest, as seen in neonatal chronic lung disease. OBJECTIVES: To determine if intratracheal treatment of newborn mice with the serine elastase inhibitor elafin would prevent MV-O2-induced lung elastin degradation and the ensuing cascade of events causing lung growth arrest. METHODS: Five-day-old mice were treated via tracheotomy with recombinant human elafin or vehicle (lactated-Ringer solution), followed by MV with 40% O2 for 8-24 hours; control animals breathed 40% O2 without MV. At study's end, lungs were harvested to assess key variables noted below. MEASUREMENTS AND MAIN RESULTS: MV-O2 of vehicle-treated pups increased lung elastase and matrix metalloproteinase-9 activity when compared with unventilated control animals, causing elastin degradation (urine desmosine doubled), TGF-ß activation (pSmad-2 tripled), and apoptosis (cleaved-caspase-3 increased 10-fold). Quantitative lung histology showed larger and fewer alveoli, greater inflammation, and scattered elastic fibers. Elafin blocked these MV-O2-induced changes. CONCLUSIONS: Intratracheal elafin, by blocking lung protease activity, prevented MV-O2-induced elastin degradation, TGF-ß activation, apoptosis, and dispersion of matrix elastin, and attenuated lung structural abnormalities noted in vehicle-treated mice after 24 hours of MV-O2. These findings suggest that elastin breakdown contributes to defective lung growth in response to MV-O2 and might be targeted therapeutically to prevent MV-O2-induced lung injury.

Vaginal mesh for prolapse: a randomized controlled trial.

OBJECTIVE: To present 3-month outcomes of a double-blind, multicenter randomized controlled trial comparing traditional vaginal prolapse surgery without mesh with vaginal surgery with mesh. METHODS: Women with pelvic organ prolapse quantification prolapse stages 2-4 were randomized to vaginal colpopexy repair with mesh or traditional vaginal colpopexy without mesh. The primary outcome measure was objective treatment success (pelvic organ prolapse quantification stage 1 or lower) at 3 months. Secondary outcome measures included quality-of-life variables and complication rates. RESULTS: Sixty-five women were recruited from January 2007 to August 2009, when the study was halted due to predetermined stopping criteria for vaginal mesh erosion at a median follow-up of 9.7 months (range, 2.4-26.7 months). Thirty-two women underwent mesh colpopexy (24 anterior mesh, eight total mesh), and 33 women had vaginal colpopexies without mesh (primarily uterosacral ligament suspension) and concurrent colporrhaphy. There were no statistically significant baseline differences between the mesh and no-mesh groups with respect to demographics, menopausal status, and race. Analysis of the mesh and no-mesh women found no difference with respect to overall recurrence (mesh: 19 [59.4%] compared with no mesh: 24 [70.4%], P=.28). There were five (15.6%) vaginal mesh erosions. Two cystotomies and one blood transfusion occurred in the mesh group only. Subjective cure of bulge symptoms was noted in 93.3% of mesh patients and 100% of no-mesh patients. Furthermore, subjective quality-of-life measurements did not differ between the two groups at baseline or 3 months postoperatively. CONCLUSION: At 3 months, there is a high vaginal mesh erosion rate (15.6%) with no difference in overall objective and subjective cure rates. This study questions the value of additive synthetic polypropylene mesh for vaginal prolapse repairs. CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov, www.clinicaltrials.gov, NCT00475540. LEVEL OF EVIDENCE: I.

Effect of partial versus complete circumferential repair on flexor tendon strength in cadavers.

PURPOSE: This study investigated the strength of epitendinous repairs covering the palmar half of the tendon circumference only. METHODS: Two hundred porcine tendons were harvested from pig feet and separated into 2 equal groups. Group 1 tendons were sutured with a 2-strand core repair and group 2 tendons were sutured with a 4-strand core repair. Each group was then divided into 5 equal subgroups (n=20). Four of the subgroups were sutured with 1 of the following epitendinous repairs: 50% simple running (50SR), complete simple running (100SR), 50% Silfverskiold (50SK), or complete Silfverskiold (100SK). One sub-group (0C) had no epitendinous repair. The core suture material was 3-0 braided polyester (Tricon; Tyco Healthcare, Dominican Republic), and the circumferential suture material was 6-0 polypropylene (Prolene, Sumerville, NJ). The tendons were mechanically strained to failure, and force data were recorded. RESULTS: The 50SR and 50SK repairs significantly increased the force at 1-mm and 2-mm gap formation of both core repairs. The 50SR and 50SK repairs increased the ultimate force at failure of both core repairs by approximately 20%. Both 50% circumferential (50C) repairs increased repair strength at the points of initial gap formation more than at the point of ultimate force. The 50C repairs were approximately 50% as strong as the 100% circumferential (100C) repairs at 1-mm and 2-mm gap formation and approximately 70% as strong at the ultimate force of failure. CONCLUSIONS: The 50C repairs increased the tensile strength of 2-strand and 4-strand tendon repairs in vitro. The prevention of early gapping was more significant than the increase of strength at failure.