Concomitant Augmentation Research Articles

Comparative assessment of adherence measures and resource use in SSRI/SNRI-treated patients with depression using second-generation antipsychotics or L-methylfolate as adjunctive therapy.

Antidepressant monotherapy is effective in achieving treatment remission in only approximately one third of patients with depression, and even switching to a second antidepressant brings the cumulative remission rate to only 50%-55%. This has led to an interest in augmentation therapy for the management of treatment-resistant depression. To assess (a) selective serotonin reuptake inhibitor/selective norepinephrine reuptake inhibitor (SSRI/SNRI) adherence when augmented with second-generation atypical antipsychotics (SGAs) or L-methylfolate using a modified application of the Healthcare Effectiveness Data and Information Set (HEDIS) acute medication management (AMM) measures at the time of augmentation, and (b) the depression-specific and total health care cost, comparing the 2 forms of augmentation therapy in the treatment of depressive disorder. Patients with a diagnosis of depression and a pharmacy claim for an SSRI/SNRI between January 1, 2006, and December 31, 2009 (index date), and receiving concomitant augmentation therapy with either an SGA or L-methylfolate (augmentation date), were identified in the MarketScan database and followed for 231 days (follow-up). Patients were excluded for having any pharmacy claim for an antidepressant or SGA 90 days pre-index; having an L-methylfolate claim 6 months pre-index; age < 18 years on the index date; or a diagnosis of pregnancy, dementia, psychotic-related mental disorders, Alzheimer's disease, or Parkinson's disease in the 12-month pre-index period. Propensity score matching (3:1 ratio, atypical antipsychotic to L-methylfolate) was used to select the final study cohorts, using covariates of age, gender, comorbidities, index SSRI/SNRI, and index SSRI/SNRI dose. Adherence to antidepressant therapy was measured from the augmentation date and included a modified application of the HEDIS (mHEDIS) AMM acute and chronic phase measures as well as the 6-month medication possession ratio. Health care utilization and cost were measured for the 6-month postaugmentation period and included both total as well as depression-related utilization/cost. Comparisons between the closely matched SGA and L-methylfolate-augmented cohorts were made using chi-square tests for binary measures and t-tests for continuous measures. Following propensity score matching, 4,053 SGA and 1,351 L-methylfolate patients were found to have augmentation of the index SSRI/SNRI within 12 months of the index date. The comparison groups were well matched on age, gender, comorbidities, and the type and dose of the SSRI/SNRI being augmented. The most common antidepressants augmented in both groups were escitalopram, duloxetine, and venlafaxine. Mean (standard deviation [SD]) time from index to augmentation was 73.5 [96.7] days for SGA and 105.9 [108.7] days for L-methylfolate (P < 0.001). The most common SGAs utilized for augmentation were quetiapine, aripiprazole, and risperidone. L-methylfolate was primarily dosed at 7.5 mg/day. The mHEDIS AMM acute phase measure was met by 68.7% of the SGA cohort and 78.7% of the L-methylfolate cohort (P < 0.001). The mHEDIS continuation phase measure was met by 50.3% of the SGA cohort and 62.1% of the L-methylfolate cohort (P < 0.001) following augmentation. Medical utilization (inpatient, emergency department, and outpatient) was significantly higher for the SGA group, while total prescription utilization was significantly higher in the L-methylfolate group. Mean [SD] total 6-month postaugmentation costs for the SGA group was $8,499 [$13,585] and $7,371 [$12,404] for the L-methylfolate group (P = 0.005), and 6-month depression-related costs were $2,688 [$4,201] for the SGA group and $1,613 [$2,315] for the L-methylfolate group (P < 0.001). Patients who augmented SSRI/SNRI therapy with SGA or L-methylfolate achieved mHEDIS AMM acute phase and continuation phase adherence scores of 69%-79% and 50%-62%, respectively. These modified scores exceeded the 2012 national median benchmarks for unmodified HEDIS AMM measures for commercial health plans. In this study, augmentation with L-methylfolate was associated with significantly higher adherence measures compared with augmentation with SGA. In addition, health care utilization and total health care costs, as well as depression-related costs, were significantly lower in the L-methylfolate augmentation group compared with augmentation with SGA.

MicroRNA miR-27b Rescues Bone Marrow–Derived Angiogenic Cell Function and Accelerates Wound Healing in Type 2 Diabetes Mellitus

Vascular precursor cells with angiogenic potentials are important for tissue repair, which is impaired in diabetes mellitus. MicroRNAs are recently discovered key regulators of gene expression, but their role in vascular precursor cell-mediated angiogenesis in diabetes mellitus is unknown. We tested the hypothesis that the microRNA miR-27b rescues impaired bone marrow-derived angiogenic cell (BMAC) function in vitro and in vivo in type 2 diabetic mice. BMACs from adult male type 2 diabetic db/db and from normal littermate db/+ mice were used. miR-27b expression was decreased in db/db BMACs. miR-27b mimic improved db/db BMAC function, including proliferation, adhesion, tube formation, and delayed apoptosis, but it did not affect migration. Elevated thrombospondin-1 (TSP-1) protein in db/db BMACs was suppressed on miR-27b mimic transfection. Inhibition of miR-27b in db/+ BMACs reduced angiogenesis, which was reversed by TSP-1 small interfering RNA (siRNA). miR-27b suppressed the pro-oxidant protein p66(shc) and mitochondrial oxidative stress, contributing to its protection of BMAC function. miR-27b also suppressed semaphorin 6A to improve BMAC function in diabetes mellitus. Luciferase binding assay suggested that miR-27b directly targeted TSP-1, TSP-2, p66(shc), and semaphorin 6A. miR-27b improved topical cell therapy of diabetic BMACs on diabetic skin wound closure, with a concomitant augmentation of wound perfusion and capillary formation. Normal BMAC therapy with miR-27b inhibition demonstrated reduced efficacy in wound closure, perfusion, and capillary formation. Local miR-27b delivery partly improved wound healing in diabetic mice. miR-27b rescues impaired BMAC angiogenesis via TSP-1 suppression, semaphorin 6A expression, and p66shc-dependent mitochondrial oxidative stress and improves BMAC therapy in wound healing in type 2 diabetic mice.

An Easy and Reliable Approach to Nipple Reduction

INTRODUCTION: The purpose of this abstract is to illustrate an easy and flexible operative approach to nipple hypertrophy. Patients with this condition often seek a more natural and harmonious appearance of their breast; this can include concomitant augmentation mammoplasty and nipple reduction. Several authors in the past have described complicated geometric designs and operations that improved only nipple height or width.1–3 This operation involves the removal of the inferior half of the nipple in a V-shape. The base is narrowed by direct closure and the superior flap is rotated inferiorly decreasing nipple height. By adjusting the amount of resection, the surgeon can easily adjust the height and width. Surgical risks are minimal and sensation is preserved. METHODS: A total of 53 female patients underwent nipple reduction from March 2005 through December 2012 by the senior author. Forty-two patients had primary augmentation with nipple reduction. Eleven patients were previously augmented and had nipple reduction as a staged procedure. Operative Technique: The incision is designed to remove the inferior half of the nipple and the base of the nipple in a V-shaped wedge. (Figures 1 and 2) The incision needs to extend into the areola 5 mm or so to achieve satisfactory reduction in nipple diameter. After removal, hemostasis is obtained, and the base of the nipple is closed using 4-0 chromic sutures. The base of the nipple is thereby reduced. If one finds the reduction is not adequate, more tissue can be removed by widening the V of the incision. The superior flap is turned down and sutured with chromic sutures, thereby reducing its projection. Postoperatively, local antibiotic ointment is applied and the patient is instructed to keep the area clean. Complete healing is accomplished in 2 weeks.Figure 1: Figure 1.Figure 2: Figure 2.RESULTS: There have been no serious complications within this cohort of patients. One patient experienced a minor dehiscence at the T portion of the nipple closure. This was treated with local wound care. Another patient requested further reduction. Patient satisfaction is high and the procedure carries very little operative risks. CONCLUSION: This procedure is safe, simple and effective for nipple hypertrophy. It can be performed concomitantly with breast augmentation procedures and sensation is preserved.

Abundance, Activity, and Diversity of Archaeal and Bacterial Communities in Both Uncontaminated and Highly Copper-Contaminated Marine Sediments

We analyzed the impact of copper mine tailing discharges on benthic Archaea and Bacteria around the city of Chanaral in northern Chile. Quantitative PCR (Q-PCR) showed that the bacteria dominated the prokaryotic community at both sites, but only the bacteria showed a decrease in abundance in the copper-contaminated site. Q-PCR on reverse transcripts indicated a higher activity of both bacterial and archaeal communities in the contaminated site, suggesting an adaptation of the two communities to copper. This hypothesis was reinforced by the concomitant augmentation of the copper-resistant copA gene coding for a P-type ATP-ase pump in the contaminated site. The metabolically active bacterial community of the contaminated site was dominated by Gammaproteobacteria related to Ectothiorhodospiraceae and Chromatiaceae and by Alphaproteobacteria phylum related to Rhodobacteraceae. The metabolically active archaeal community was dominated by one lineage belonging to unclassified Euryarchaeota and to methanogenic Archaea.

Laparoscopic and robot‐assisted continent urinary diversions (Mitrofanoff and Yang‐Monti conduits) in a consecutive series of 15 adult patients: the Saint Augustin technique

To present a series of 15 laparoscopic and robot-assisted Mitrofanoff and Yang-Monti vesicostomies in an adult population, and to assess the feasibility and safety of these minimally invasive approaches. Between 2009 and 2012, 15 patients underwent laparoscopic (n = 11) or robot-assisted (n = 4) construction of vesicostomy by a single surgeon (D.R.): Mitrofanoff appendicovesicostomy (n = 11) or double Yang-Monti ileal conduit (n = 4). Fourteen patients underwent concomitant augmentation enterocystoplasty. Indications for surgery included neurogenic bladder (n = 11) and urethral dysfunction (n = 4). The patients were evaluated postoperatively using cystography. Quality of life (QoL) was evaluated using an internally developed questionnaire. All surgeries were successfully completed with no conversions. Operating time was always <5 h. The mean estimated blood loss was 150 mL and the mean follow-up was 22 months. Early postoperative complications included deep retrovesical abscess (n = 2) and upper urinary tract infections (n = 4), and one patient had peri-operative cardiac failure. Late postoperative complications included stomal stenosis (n = 2), persistent low-pressure bladder incontinence (n = 1) and recurrent infections (n = 1). Surgical excision of the conduit was necessary in one patient. Postoperatively, patients showed complete bladder emptying and no leak on follow-up cystography. According to our QoL questionnaire, 13/15 patients did not regret the surgery. While a longer follow-up is needed to assess the durability of our results, this series shows that the laparoscopic and robot-assisted approaches for the construction of continent urinary diversions are feasible and safe in an adult population.

Combined surgical therapy of advanced peri‐implantitis lesions with concomitant soft tissue volume augmentation. A case series

Mucosal recessions are a common finding following surgical treatment of peri-implantitis, thus compromising the overall esthetic outcome of implant therapy. This case series aimed at evaluating the clinical outcome of a combined surgical therapy of advanced peri-implantitis lesions with concomitant soft tissue volume augmentation. Ten patients (n = 13 implants exhibiting combined supra- and intrabony defects) underwent access flap surgery, implantoplasty at bucally and supracrestally exposed implant parts, and augmentation of the intrabony components using a natural bone mineral and a native collagen membrane after surface decontamination. A subepithelial connective tissue graft was harvested from the palate and adapted to the wound area to support transmucosal healing. Clinical parameters (i.e. bleeding on probing--BOP; probing depths--PD; mucosal recession--MR; clinical attachment level--CAL) were recorded at baseline and after 6 months. At 6 months, the combined surgical procedure was associated with a significant reduction in mean BOP (74.39 ± 28.52%), PD (2.53 ± 1.80 mm), and CAL (2.07 ± 1.93 mm) values. Site-level analysis has pointed to a slight increase in mean mucosal height (0.07 ± 0.5 mm) at the buccal aspects (i.e. mb, b, db). The combined surgical procedure investigated may be effective in controlling advanced peri-implantitis lesions without compromising the overall esthetic outcome in the short term.

Abstract 19517: Pro-Angiogenic MicroRNA-27b Retards EPC Apoptosis and Accelerates Wound Healing in Type 2 Diabetes via Suppressing p53 and Bax/Bcl-2 Ratio

Introduction: Endothelial progenitor cells (EPCs) are promising candidates for autologous cell therapy of diabetic wound repair because of their high angiogenic potentials. However, increased EPC apoptosis in diabetes directly limits its clinical success. MicroRNAs are endogenous non-coding RNAs that regulate gene expression at the post-transcriptional level, but their roles in EPC-mediated angiogenesis in diabetes are incompletely understood. We hypothesized that the pro-angiogenic miR-27b inhibits EPC apoptosis and improves wound healing in type 2 diabetes. Methods and Results: Bone marrow-derived EPCs from adult male type 2 diabetic db/db mice and their normal littermates db/+ mice were used. MiR-27b expression (real-time PCR) in EPCs was decreased by &gt;66% in db/db vs. db/+ mice (n=4, p&lt;0.05). The impaired EPC angiogenesis of &gt;70% (Matrigel tube formation, n=4, vs. db/+) and increased EPC apoptosis (TUNEL staining, n=3, p&lt;0.05 vs. db/+) in diabetes were rescued following miR-27b mimic transfection (n=3, p&lt;0.05 vs. db/db + scramble). p53 and Bax/Bcl-2 ratio in EPCs (Western blot analyses) were significantly higher in db/db mice (by 23% and 58%, respectively, vs. db/+), which were suppressed by miR-27b mimic (n=3, p&lt;0.05 vs. db/db + scramble). Excisional wound (6-mm diameter) closure was markedly delayed in db/db vs. db/+ mice (n=5, p&lt;0.05), accompanied by poorer wound angiogenesis (Laser Doppler detection, n=5, p&lt;0.05) and elevated expression of p53 (&gt; 72%) and Bax/Bcl-2 ratio (&gt; 55%) (both n=5 vs. db/+). Local delivery of miR-27b mimic or cell therapy using diabetic EPCs (10 6 ) with miR-27b mimic transfection significantly accelerated wound closure rates (n=5, p&lt;0.05), with a concomitant augmentation of wound perfusion in db/db mice (n=5, p&lt;0.05). Conclusion: miR-27b retards EPC apoptosis and accelerates wound healing in type 2 diabetic mice, at least in part, via suppressing p53 and Bax/Bcl-2 ratio. These findings may provide a mechanistic basis for rescuing EPC dysfunction in diabetes for successful autologous cell therapy.

Posterior Leaflet Augmentation in Ischemic Mitral Regurgitation Increases Leaflet Coaptation and Mobility

Restoring leaflet coaptation is the primary objective in repair of ischemic mitral regurgitation (IMR). The common practice of placing an undersized annuloplasty ring partially achieves this goal by correcting annular dilation; however, annular reduction has been demonstrated to exacerbate posterior leaflet tethering. Using a sheep model of IMR, we tested the hypothesis that posterior leaflet augmentation (PLA) combined with standard annuloplasty sizing increases leaflet coaptation more effectively than undersized annuloplasty alone. Eight weeks after posterobasal myocardial infarction, 15 sheep with 2+ or greater IMR underwent annuloplasty with either a 24-mm annuloplasty ring (24-mm group, n = 5), 30-mm ring (30-mm group, n = 5), or 30-mm ring with concomitant augmentation of the posterior leaflet (PLA group, n = 5). Using three-dimensional echocardiography, postrepair coaptation zone and posterior leaflet mobility were assessed. Leaflet coaptation length after repair was greater in the PLA group (4.1 ± 0.3 mm) and the 24-mm group (3.8 ± 0.5 mm) as compared with the 30-mm group (2.7 ± 0.6 mm, p < 0.01). Leaflet coaptation area was significantly greater in the PLA group (121.5 ± 6.6 mm(2)) as compared with the 30-mm group (77.5 ± 17.0 mm(2)) or the 24-mm group (92.5 ± 17.9 mm(2), p < 0.01). Posterior leaflet mobility was significantly greater in the PLA group as compared with the 30-mm group or the 24-mm group. Posterior leaflet augmentation combined with standard-sized annuloplasty enhances leaflet coaptation more effectively than either standard-sized annuloplasty or undersized annuloplasty alone. Increased leaflet coaptation after PLA provides redundancy to IMR repair, and may decrease incidence of both recurrent IMR and mitral stenosis.

A LACK OF DELAYED INTRAOCULAR PRESSURE ELEVATION IN PATIENTS TREATED WITH INTRAVITREAL INJECTION OF BEVACIZUMAB AND RANIBIZUMAB

The purpose of this study was to report the rate of intraocular pressure (IOP) elevation after intravitreal injections of anti-vascular endothelial growth factor agents for exudative age-related macular degeneration. Retrospective chart review of all patients receiving intravitreal ranibizumab and/or bevacizumab injections for exudative age-related macular degeneration from November 2005 to June 2010. Delayed ocular hypertension (OHT) was defined as either an IOP ≥22 mmHg on 2 consecutive visits (with an increase from baseline >6 mmHg) or an IOP >26 mmHg on a single visit with a concomitant initiation or augmentation of IOP-lowering treatment. Noninjected fellow eyes served as controls. Incidence of delayed OHT was analyzed using survival analyses, with risk assessed by Cox proportional hazards regression models. Eyes with glaucoma were evaluated separately. Three hundred and two treated eyes and 226 control eyes met inclusion criteria. In eyes with exudative age-related macular degeneration without glaucoma, 3 of 270 injected eyes (0.51% incidence per eye-year) developed delayed OHT compared with 4 of 195 control eyes (1.00% incidence per eye-year), a difference that was not statistically significant (hazard ratio = 0.48; 95% confidence interval: 0.11-2.23). In eyes with exudative age-related macular degeneration and glaucoma, 2 of 32 injected eyes developed delayed OHT (3.1% incidence per eye-year) compared with 3 of 31 control eyes (5.7% incidence per eye-year), a difference that was not statistically significant (hazard ratio = 0.59; 95% confidence interval: 0.10-3.60). The incidence of delayed OHT after intravitreal anti-vascular endothelial growth factor injections was low and did not differ between injected and control eyes, including eyes with glaucoma. These results argue against a significant risk of IOP elevation because of repeated anti-vascular endothelial growth factor therapy.

608 BLADDER DECOMPENSATION AFTER CONTINENT URINARY RECONSTRUCTION IN CHILDREN WITH NEUROGENIC BLADDER

You have accessJournal of UrologyPediatrics: Bladder Dysfunction - Myelodysplasia, Voiding Dysfnction, Enuresis1 Apr 2012608 BLADDER DECOMPENSATION AFTER CONTINENT URINARY RECONSTRUCTION IN CHILDREN WITH NEUROGENIC BLADDER William DeFoor, Bezalel Sivan, Pramod Reddy, Eugene Minevich, Curtis Sheldon, and Shumyle Alam William DeFoorWilliam DeFoor Cincinnati, OH More articles by this author , Bezalel SivanBezalel Sivan Cincinnati, OH More articles by this author , Pramod ReddyPramod Reddy Cincinnati, OH More articles by this author , Eugene MinevichEugene Minevich Cincinnati, OH More articles by this author , Curtis SheldonCurtis Sheldon Cincinnati, OH More articles by this author , and Shumyle AlamShumyle Alam Cincinnati, OH More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2012.02.685AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Continent urinary reconstruction in children with neurogenic bladder often includes bladder outlet procedures to provide urinary incontinence as well as a Mitrofanoff neo-urethra to facilitate clean intermittent catheterization. Medical management is maximized pre-operatively to avoid the need for concomitant bladder augmentation. It has been suggested by some investigators that enterocystoplasty should be avoided at all cost. The purpose of this study is to report outcomes in children who developed bladder decompensation after this course of treatment. METHODS A retrospective cohort study was performed of all children with neurogenic bladder who underwent continent lower urinary reconstruction without bladder augmentation at a single institution from 2006 to 2010. Inclusion criteria included those patients who developed bladder deterioration post-operatively Surgical details, urodynamic data, and imaging results were abstracted from the medical record. Comparisons between continuous variables were performed with a t-test. RESULTS A total of 5 patients were identified (3 males and 2 females). The mean age was 9.3 years with a mean follow-up of 3 years. All patients had a diagnosis of myelomeningocele or tethered cord. All patients had a Young-Dees-Leadbetter bladder neck reconstruction as well as a urethral sling but no bladder augmentation. Pre-operatively, all patients had a smooth-walled, low-pressure bladder, with no vesico-ureteral reflux. The mean maximal capacity was 329 ml. At a mean time of 7.6 months post-operatively, all patients had developed a towering, trabeculated bladder with a thickened detrusor muscle. The mean maximal capacity decreased to 184 ml (p = 0.01). All patients were found to have higher filling detrusor pressures. Three patients developed hydronephrosis and two were found to have new vesico-ureteral reflux with renal injury. Four had urinary incontinence. Two were found to have re-tethering of their spinal cord. Despite maximal doses of anti-cholinergic medication, 3 patients were recommended to undergo bladder augmentation. One patient underwent injection of Botulinum A toxin. CONCLUSIONS Despite recent reports that bladder augmentation is not necessary in children with neurogenic bladder, some patients do develop hostile bladder dynamics after continence procedures that can lead to upper tract deterioration. Further studies are needed to help determine patients who are at risk of bladder decompensation that may be better served with initial enterocystoplasty. © 2012 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 187Issue 4SApril 2012Page: e247-e248 Advertisement Copyright & Permissions© 2012 by American Urological Association Education and Research, Inc.MetricsAuthor Information William DeFoor Cincinnati, OH More articles by this author Bezalel Sivan Cincinnati, OH More articles by this author Pramod Reddy Cincinnati, OH More articles by this author Eugene Minevich Cincinnati, OH More articles by this author Curtis Sheldon Cincinnati, OH More articles by this author Shumyle Alam Cincinnati, OH More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

V544 SIMULTANEOUS ROBOTIC ASSISTED LAPAROSCOPIC CONTINENT CATHETERIZABLE CHANNELS: THE SPLIT APPENDIX TECHNIQUE

You have accessJournal of UrologyPediatrics1 Apr 2012V544 SIMULTANEOUS ROBOTIC ASSISTED LAPAROSCOPIC CONTINENT CATHETERIZABLE CHANNELS: THE SPLIT APPENDIX TECHNIQUE Dennis Liu, Marcelo Orvieto, and Mohan Gundeti Dennis LiuDennis Liu Chicago, IL More articles by this author , Marcelo OrvietoMarcelo Orvieto Chicago, IL More articles by this author , and Mohan GundetiMohan Gundeti Chicago, IL More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2012.02.618AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Creation of continent catheterizable channels with and without augmentation is often necessary for children with neurogenic bladders to obtain fecal [Malone Antegrade Continent Enema (MACE)] and urinary continence (Mitrofanoff Appendicovesicostomy). Traditionally, these channels have been created with open surgery, often requiring creation of a Monti channel and/or a cecal flap. We present our experience with simultaneous robotic assisted laparoscopic Mitrofanoff Appendicovesicostomy (RALMA) and robotic assisted laparoscopic MACE (RALMACE) using the split appendix technique, enabling creation of both channels using solely the appendix. METHODS The patient is positioned in a modified 25° trendelenburg position with legs positioned in Allen stirrups. A 12 mm camera port is placed 12 cm superior to the pubic symphysis and 2 8 mm robotic ports are placed on either side of the camera port. An assistant port is placed in the left upper quadrant. The appendix is isolated and split into a 5 cm distal segment for use as the Mitrofanoff and the proximal 2 cm for use as the MACE. The appendicovesicostomy is created by formation of an anti-refluxing tunnel in the anterior wall of the bladder. When concomitant augmentation cystoplasty is performed, the appendicovesicostomy is tunneled intravesically in the posterior wall of the bladder. The appendicovesicostomy is brought out to the skin at the umbilicus. The MACE is brought out in the right lower quadrant without imbrication. Stomas are matured using the V-flap technique. RESULTS We have performed the RAL split appendix technique in three patients. Two of the patients also required augmentation cystoplasty while one did not. Fecal and urinary continence has been obtained in all patients and no complications have been encountered. CONCLUSIONS Simultaneous RAL creation of the Mitrofanoff appendicovesicostomy and MACE using the split appendix is an effective minimally invasive surgical technique that avoids the need for a Monti channel. Longer follow-up and comparison with open surgery are needed to confirm the utility of this approach. © 2012 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 187Issue 4SApril 2012Page: e223 Advertisement Copyright & Permissions© 2012 by American Urological Association Education and Research, Inc.MetricsAuthor Information Dennis Liu Chicago, IL More articles by this author Marcelo Orvieto Chicago, IL More articles by this author Mohan Gundeti Chicago, IL More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Combined Method of Bladder Neck Closure and Concomitant Augmentation Cystoplasty in the Setting of Refractory Urinary Incontinence

To describe the technique of concomitant bladder neck closure and augmentation cystoplasty in a 22-year-old woman with a history of bladder exstrophy and refractory urinary incontinence. This patient had prior augmentation cystoplasty and circumferential fascial urethral sling placement with continued incontinence. During closure of the bladder neck, the bladder neck was incorporated into the augmentation cystoplasty to help prevent failure of bladder neck closure. The patient had previously undergone augmentation cystoplasty, circumferential fascial urethral sling placement, and antegrade collagen injection of the bladder neck. Despite these interventions, she continued to have refractory urinary incontinence. Her bladder neck was closed by incorporating the bladder neck into the cystotomy and using the bladder neck as an edge of anastomosis during augmentation cystoplasty. The patient tolerated the procedure well. She catheterizes easily through her appendicovesicostomy and has remained continent. She has no leakage from her closed bladder neck 30 months after closure. Incorporating the bladder neck into the cystotomy during a planned augmentation cystoplasty and bladder neck closure should be considered as an alternative to separate bladder neck closure, which can fail and can result in continued urinary incontinence.

Abstract 17288: GTP Cyclohydrolase I Rescues microRNA-34a Impairment of Endothelial Progenitor Cell Angiogenesis in Aging

Introduction: Endothelial progenitor cells (EPCs) are critically regulated by eNOS for their angiogenic functions. eNOS and its essential cofactor tetrahydrobiopterin (BH4) are reduced during aging, and aged EPCs exhibit decreased proliferation, migration and survival. We recently reported that microRNA 34a (miR-34a) induces EPC senescence and inhibits its angiogenesis by targeting silent information regulator 1 (SIRT1). However, whether miR-34a regulation of EPC angiogenesis involves eNOS and BH4 in aging is unknown. We hypothesized that miR-34a promotes impairment of EPC angiogenesis in aging, which could be rescued by GTP cyclohydrolase I (GTPCH I, the rate-limiting enzyme for BH4 biosynthesis). Methods: Bone marrow-derived EPCs from young (8-10 weeks) C57BL/6 (wild type, WT), GTPCH I transgenic (Tg-GCH, endothelial-specific GTPCH I overexpression), hph-1 (BH4-deficient), aged (18-20 months) C57BL/6 (WT) and eNOS/GCH double-transgenic (Tg-eNOS/GCH) mice (all males) were used. Results: Aged WT mice showed significantly impaired recovery of hindlimb ischemia, compared with young WT mice (0.40±0.13 vs. 0.68±0.12, n=3, p&lt;0.05). Consistently, EPCs from aged WT mice showed impaired Matrigel angiogenesis (0.46±0.03 vs. 1.00±0.04, n=4, p&lt;0.01). Reactive oxygen species (ROS) level was significantly elevated in EPCs from aged WT mice (~1.6 folds vs. young WT mice, n=3, p&lt;0.05), accompanied by reduced GTPCH I expression (0.63±0.07 vs. 1.00±0.08, n=3, p&lt;0.05). Suppression of miR-34a in EPCs from aged WT mice rescued their impaired angiogenesis, while overexpression of miR-34a in EPCs from young WT mice impaired their angiogenesis in vitro. Moreover, miR-34a expression was decreased in EPCs from aged Tg-eNOS/GCH double-transgenic mice vs. aged WT mice (0.83±0.07 vs. 1.91±0.07, n=3, p&lt;0.01), with a concomitant augmentation of SIRT1 level (1.14±0.02 vs. 0.54±0.06, n=3, p&lt;0.01). Finally, miR-34a expression was down-regulated in EPCs from Tg-GCH mice with an increase in SIRT1 level, and was up-regulated in EPCs from BH4-deficient hph-1 mice with a decrease in SIRT1 level vs. WT mice. Conclusion: These findings demonstrate, for the first time, that miR-34a promotes impairment of EPC angiogenesis in aging, which could be rescued by GTPCH I/BH4.

Microbial dechlorination of chloroorganics and simultaneous decolorization of pulp–paper mill effluent by Pseudomonas putida MTCC 10510 augmentation

The physicochemical analyses of pulp-paper mill effluent revealed that it was dark brown with 1761 ± 2.3 color PtCo units having slightly alkaline pH, high biological oxygen demand and chemical oxygen demand values, and contained large quantities of organic and inorganic constituents, well above the prescribed standards. The bacterial growth, color reduction, and dechlorination were evident in all the four sets of experiments with different possible combinations of nutrient supplementation and Pseudomonas putida augmentation. A high degree of decolorization at 29.7% and 27.4% was observed by the effluent native microflora during 48 and 24 h, in unaugmented effluent supplemented with glucose + yeast extract and glucose + peptone, respectively. The extent of decolorization in glucose + yeast extract unaugmented effluent also corresponded with high degree of dechlorination (59.3%) during 60-h incubation (SET III). An appreciable level of growth, decolorization, and dechlorination was evident in nutrient unsupplemented P. putida augmented effluent as well as in the control natural effluent. However, a maximum level of growth response (OD 1.641-1.902) during 36-48 h, removal of color (39.72-48.2%) during 24-36 h, and chloride ions (80.1-83.5%) during 36 h was achieved in P. putida augmented effluent supplemented with glucose + yeast extract or peptone. Therefore, supplementation of effluent with glucose and yeast extract or peptone and concomitant augmentation with P. putida is required for efficient effluent decolorization and detoxification.

Posterior leaflet augmentation improves leaflet tethering in repair of ischemic mitral regurgitation

Ischemic mitral regurgitation results from annular dilatation, leaflet tethering and leaflet flattening. Undersized annuloplasty corrects annular dilatation but worsens leaflet tethering and flattening. This exacerbation of abnormal leaflet geometry may contribute to poor repair results for ischemic mitral regurgitation (IMR). Using a sheep model of IMR, we hypothesized that posterior leaflet augmentation and less-extreme annular undersizing would relieve tethering and increase leaflet curvature. Eight weeks after posterolateral infarct, 10 sheep with ≥ 2+ IMR underwent either a 24-mm planar ring annuloplasty (n = 5) or a 30-mm planar ring annuloplasty with concomitant posterior leaflet augmentation (n = 5). Real-time three-dimensional echocardiography allowed measurement of indices of leaflet curvature and tethering before and after annuloplasty. Comparing pre- and post-repair values in the P1, P2, and P3 leaflet regions, undersized 24-mm ring annuloplasty made no significant difference to mean septolateral curvature (0.23-0.26, 0.33-0.29, and 0.27-0.37 cm(-1), respectively), whereas leaflet augmentation in combination with a 30-mm ring annuloplasty increased septolateral curvature (P1 0.30-1.02, P2 0.31-1.23, and P3 0.35-0.84 cm(-1), p-values<0.05). The mean tethering angle formed between the annular plane and the posterior leaflet increased in all three posterior regions for the 24-mm ring group (P1 12-23°, P2 26-31°, and P3 16-25°), but decreased in all regions for the group undergoing leaflet augmentation (P1 +5 to -6°, P2 +13 to -13°, P3 +16-15°, all p-values < 0.05). Undersized annuloplasty exacerbates leaflet tethering. Posterior leaflet augmentation with less severe annular reduction increases leaflet curvature and decreases tethering; this technique more completely addresses the pathogenic mechanism of IMR and may improve repair durability.

Total Continence Reconstruction Using the Artificial Urinary Sphincter and the Malone Antegrade Continence Enema

Surgical management of children with myelomeningocele addresses 2 aspects of the disease, neurogenic bladder and neurogenic bowel. Results of total continence reconstruction using an artificial urinary sphincter and Malone antegrade continence enema are presented. We performed a retrospective chart review of patients who underwent simultaneous artificial urinary sphincter placement and a Malone antegrade continence enema procedure. From 1997 to 2007 a total of 21 patients with myelomeningocele underwent total continence reconstruction using the artificial urinary sphincter. Mean patient age was 10.4 years (range 6 to 22) and mean followup was 4.7 years (range 0.66 to 11.7). Artificial urinary sphincter cuff was placed around the bladder neck. A Malone antegrade continence enema was performed using appendix in 19 patients and cecal based flaps in 2. Two patients underwent concomitant augmentation cystoplasty. Six patients had concomitant Mitrofanoff vesicostomy using split appendix in 4 and Monti tube in 2. Immediate postoperative complications were observed in 5 patients, including prolonged ileus (2), urinary tract infection (2) and superficial wound dehiscence (1). Seventeen patients (81%) achieved complete urinary continence and 5 were voiding with sphincter cycling. Improvement in urinary continence with dry intervals greater than 3 hours was reported in 2 patients. There were 19 patients (90%) who reported fecal continence, with 2 reporting soiling 1 to 2 times a week. Malone antegrade continence enema stoma stenosis occurred in 3 patients and 2 required revisions. Sixteen patients (76%) achieved complete continence of stool and urine. During followup 2 artificial urinary sphincters were explanted and 8 patients (38%) underwent bladder augmentation. Urinary and fecal continence in patients with myelomeningocele is achievable with a single total continence reconstruction procedure using the artificial urinary sphincter and the Malone antegrade continence enema with durable results.

747 OBJECTIVE MEASUREMENT OF QUALITY OF LIFE CHANGES AFTER ACE MALONE USING THE FICQOL SURVEY

You have accessJournal of UrologyPediatrics: Bladder Dysfunction - Myelodysplasia, Voiding Dysfunction, Enuresis1 Apr 2010747 OBJECTIVE MEASUREMENT OF QUALITY OF LIFE CHANGES AFTER ACE MALONE USING THE FICQOL SURVEY Joon-ha Ok, Hao G. Nguyen, and Eric A. Kurzrock Joon-ha OkJoon-ha Ok More articles by this author , Hao G. NguyenHao G. Nguyen More articles by this author , and Eric A. KurzrockEric A. Kurzrock More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2010.02.1273AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES The Malone antegrade continence enema (ACE) procedure has revolutionized the treatment of neuropathic bowel disorders. Despite the dramatic results in relieving constipation and fecal incontinence, there is no objective data demonstrating improved quality of life. We previously developed and published a reliable and valid instrument for measuring the impact of fecal incontinence and constipation on quality of life (FICQOL) of caregivers and their children with spina bifida. The items are divided into 7 QOL factor groupings: bowel program, dietary management, symptoms, travel and socialization, family relationships, and impact upon the caregiver emotionally and financially. This instrument was utilized in a prospective study to discriminate changes in QOL after application of the ACE procedure. METHODS Between 2002 and 2008, 75 families were evaluated prospectively with the FICQOL survey. Families of children who had an ACE procedure and completed the survey before surgery and a minimum of 6 months after surgery were included. The ACE procedure was done laparoscopically in 75% of the patients with the remaining undergoing open ACE with concomitant bladder augmentation. The items on the FICQOL before and after surgery were compared with Wilcoxon signed rank test. Statistical significance was defined at P<0.05. RESULTS We identified 20 children who met the inclusion criteria. After an ACE Malone the mean number of bowel movements (BM) per day decreased from 2 to 1.2 along with a decrease in number of BM accidents per week from 3.8 to 0.3. There was no change in the time committed to bowel care which was about 45 minutes. The percentage of patients taking oral laxatives decreased from 63% to 5%. Both parent and child were less often prevented from leaving the house due to bowel care. Caretakers' bother, anxiety and depression due to bowel care decreased. Although factors regarding the child's social issues and parent's employment improved, the changes were not statistically significant. The most dramatic score changes were in decreased worry of both parent and child about the smell of fecal incontinence. CONCLUSIONS Application of the FICQOL instrument objectively demonstrates that the ACE Malone procedure eliminates fecal incontinence and improves many quality of life factors for parents and children with neuropathic fecal incontinence and constipation. Without changing the amount of time necessary for bowel care, the ACE procedure decreases the families' worries and anxieties and allows them to leave the home with confidence. Sacramento, CA© 2010 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 183Issue 4SApril 2010Page: e292 Advertisement Copyright & Permissions© 2010 by American Urological Association Education and Research, Inc.MetricsAuthor Information Joon-ha Ok More articles by this author Hao G. Nguyen More articles by this author Eric A. Kurzrock More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Detrusor Wrap-Around Bladder Neck (DRBN) for Treatment of Urinary Incontinence Following Exstrophy Closure

Purpose The use of a demucosalized detrusor pedicle flap as a bladder neck wrap was described by Mitchell. The outcome of this novel technique of bladder neck reconstruction (BNR) in 28 children with bladder exstrophy is presented. Material and Methods The records of all patients who underwent bladder neck reconstruction using DWBN were reviewed. A total of 28 patients were identified and included 21 boys and 7 girls with mean age at surgery of 8.3 years. All patients had previous exstrophy closure (17 staged & 11 complete). Eight patients (29%) had previous endoscopic injection of bulking agent at the bladder neck. At time of surgery 13 patients (46%) required concomitant augmentation ilepcystoplasty and continent catheterizable outlet. Ureteral reimplantation was not performed in any patient. Continence was defined as complete dryness for a minimum of 4 hours. Results Mean follow-up duration is 31 months (range 13-48). All augmented patients were on CIC through the continent outlet. Complete dryness was achieved in 20/28 patients (71%). However, continence rate was only 47% in the non augmented group compared to 100% in the augmented group. Six of the incontinent children underwent bladder neck injection using bulking agent but dryness was achieved only in 1 (17%). Conclusions DWBN is a viable option for bladder neck reconstruction for incontinent children after exstrophy closure. However, bladder augmentation and continent outlet construction are the pillars of optimal success. Injection of bulking agent at the bladder neck for failures has poor success.

A novel signaling pathway associated with Lyn, PI 3-kinase and Akt supports the proliferation of myeloma cells

Interleukin-6 (IL-6) is a growth factor for human myeloma cells. We have recently found that in myeloma cells the activation of both signal transducer and activator of transcription (STAT) 3 and extracellular signal-regulated kinase (ERK) 1/2 is not sufficient for the IL-6-induced proliferation, which further requires the activation of the src family kinases, such as Lyn. Here we showed that the Lyn-overexpressed myeloma cell lines had the higher proliferative rate with IL-6 and the enhanced activation of the phosphatidylinositol (PI) 3-kinase and Akt. The IL-6-induced phosphorylation of STAT3 and ERK1/2 was not up-regulated in the Lyn-overexpressed cells, indicating that the Lyn-PI 3-kinase-Akt pathway is independent of these pathways. The PI 3-kinase was co-precipitated with Lyn in the Lyn-overexpressed cells of which proliferation with IL-6 was abrogated by the specific inhibitors for PI 3-kinase or Akt, suggesting that the activation of the PI 3-kinase-Akt pathway associated with Lyn is indeed related to the concomitant augmentation of myeloma cell growth. Furthermore, the decreased expression of p53 and p21 Cip1 proteins was observed in the Lyn-overexpressed cells, implicating a possible downstream target of Akt. This study identifies a novel IL-6-mediated signaling pathway that certainly plays a role in the proliferation of myeloma cells and this novel mechanism of MM tumor cell growth associated with Lyn would eventually contribute to the development of MM treatment.

Long‐term outcomes and patient satisfaction of continent catheterizable limb and augmentation cystoplasty simultaneous with salvage prostatectomy

We evaluated the long-term outcomes of augmentation cystoplasty and continent catheterizable limb formation in patients who underwent simultaneous salvage prostatectomy. Twelve men who underwent salvage prostatectomy with augmentation cystoplasty and either an appendicovesicostomy or Monti ileovesicostomy between October 2000 and February 2003 were assessed for long-term surgical complications, reoperations, continence rates, and patient satisfaction using the Incontinence Symptom Index (ISI) questionnaire and a self-designed catheterization questionnaire. In addition to bladder augmentation, six patients underwent appendicovesicostomy, four had a Monti ileovesicostomy and two a spiral Monti ileovesicostomy. There were no intraoperative complications or surgical-related deaths. Four patients required revision surgery (33%) at a mean of 39 months. Minor revisions were performed for stomal stenosis in two patients with stomal relocation in two patients. Ten of 12 patients were dry (83.3%) with a catheterization frequency of between 3 and 8 hr. At a mean follow-up of 61 months (SD = 20.51), the mean ISI severity score was 1.86 (SD = 3.54) and the mean ISI bother score was 1 (SD 0.74). The majority (86%) would choose to undergo the surgery again. Although surgically challenging and associated with significant morbidity, salvage prostatectomy with concomitant bladder augmentation and continent catheterizable reconstruction is a feasible and effective means of obtaining adequate long-term urinary continence, while preserving the native bladder. In comparison to similar historical patients with catheterizable limbs only, fewer of the augmented patients needed antimuscarinic medication and delayed augmentation was not necessary. Complications do not increase over time and the continence rates are stable.