A Comparison of Sacrospinous Hysteropexy Augmented With Polypropylene Mesh Versus Human Dermis at 12-Month Follow-up: An Ambidirectional Study.

BACKGROUND: Suture-based hysteropexy is performed for pelvic organ prolapse with varying results. Graft augmentation may improve outcomes. OBJECTIVE: The aim of this study was to determine whether vaginal hysteropexy with mesh reduces recurrence at 1-year postoperative examination compared with hysteropexy with allograft. METHODS: Data were collected for patients who underwent vaginal hysteropexy with either mesh "Uphold" (referred to as "mesh") or a cadaveric allograft "Axis or Repliform" (referred to as "dermal"). The primary outcome was anatomic success defined as no prolapse Pelvic Organ Prolapse Quantification System stage II or less at 12 months postoperative. The secondary outcomes were recurrence to the hymen and a composite score (any positive response to the 20-item Pelvic Floor Distress Inventory question 3 and cervix ≥ -1/2 total vaginal length at rest or as reference point 3 cm proximal to or above the hymenal ring anteriorly [Ba] ≥0) measured at 12 months. RESULTS: Two hundred seventy-four patients returned for their 1-year postoperative examination: 93.5% of the mesh group (231/247 subjects) and 95.5% of the dermal group (43/45 subjects). The mesh group had fewer recurrences to or beyond Pelvic Organ Prolapse Quantification System stage II (mesh 18% vs dermal 29%, P = 0.03), to the hymen (2.6% vs 9.3%, P = 0.007), or based on composite score (19 vs 33%, P = 0.007). Questionnaire data improved more in the mesh group (P < 0.0001). The exposure rate was 5.75% (13/247) in the mesh group. Reoperation rate was greater in the dermal group (mesh 4.3%vs dermal 7.3%, P = 02). CONCLUSIONS: Hysteropexy augmented with mesh reduced the recurrence at 1 year compared with hysteropexy with allograft. Fewer patients in the mesh group felt a bulge at 1 year (4.5% vs 20.9%, P < 0.0001). These findings need to be weighed against the mesh exposure rate of 5.75%.

Anterior Colporrhaphy With and Without Dermal Allograft: A Randomized Control Trial With Long-Term Follow-Up.

OBJECTIVE: The objective of this study was to determine whether anterior colporrhaphy plus insertion of anterior dermal allograft reduces anterior prolapse recurrence at 1 and 7 to 10 years postoperatively compared with anterior colporrhaphy alone. METHODS: We present a nonblinded randomized controlled trial with 1- and 7- to 10-year follow-up. Subjects were randomized between 2005 and 2008 to anterior colporrhaphy or ultralateral anterior colporrhaphy plus insertion of a dermal allograft spanning the anterior compartment between the arcus tendineus fascia pelvis on each side. Eligible subjects had anterior prolapse to the hymen or beyond, were bothered by their prolapse, and were planning to undergo surgical correction. Subjects completed a pelvic organ prolapse quantification system (POPQ) examination and Pelvic Floor Distress Inventory (PFDI)/PFDI-20 before surgery; a POPQ, PFDI, and Pelvic Organ Prolapse/Incontinence Sexual Questionnaire at 1 year postoperatively; and a POPQ, PFDI-20, Pelvic Organ Prolapse/Incontinence Sexual Questionnaire, Revised, and Patient-reported Global Impression of Improvement Inventory at 7 to 10 years postoperatively. Our primary outcome was anatomic anterior prolapse recurrence at 1 or 7 to 10 years defined as Aa or Ba greater than or equal to -1. Our secondary outcome was a composite score of anterior prolapse recurrence at 1 or 7 to 10 years defined as anatomic recurrence (Aa or Ba ≥ 0), retreatment for cystocele, or answering yes to PFDI-20 question 3 (subjective report of vaginal bulge). RESULTS: A total of 114 subjects were randomized, 70 to anterior colporrhaphy and 44 to anterior colporrhaphy plus dermal allograft. About 92% of subjects underwent concomitant apical suspension, 98% in the graft group and 89% in the nongraft group. Eighty-nine subjects (32 graft [73%], 57 nongraft [81%]) returned for 1-year follow-up. Fifty-three patients (19 graft [48%], 34 nongraft [49%]) returned for 7- to 10-year follow-up. The primary outcome was met by 8 (18%) graft and 22 (31%) nongraft subjects at 1 year postoperatively (P = 0.26) and by 10 (23%) graft and 24 (34%) nongraft subjects at 7 to 10 years postoperatively (P = 0.37). The secondary outcome was met by 8 (18%) graft and 15 (21%) nongraft subjects at 1 year postoperatively (P = 0.74) and by 13 (30%) graft and 21 (30.0%) nongraft subjects at 7 to 10 years postoperatively (P = 0.99). CONCLUSIONS: We cannot conclude whether there is a difference in anterior recurrence for anterior colporrhaphy with and without dermal allograft and do not recommend changes in clinical practice based on these results.

Does physician specialty affect persistence to pharmacotherapy among patients with overactive bladder syndrome?

INTRODUCTION AND HYPOTHESIS: We compared persistence on overactive bladder (OAB) pharmacotherapy in patients treated in the Female Pelvic Medicine and Reconstructive Surgery (FPMRS) department compared with patients treated in the Internal Medicine (IM) and General Urology (GU) departments within an integrated health-care system. We hypothesized that persistence would be higher among FPMRS patients. METHODS: This was a retrospective cohort study. Patients with at least one prescription for OAB between January 2003 and July 2014 were identified. Demographic, prescription and treatment specialty data and data on the use of third-line therapies were collected. The primary outcome was persistence, defined as days on continuous pharmacotherapy. Discontinuation was defined as a treatment gap of ≥45 days. Discontinuation-free probabilities were calculated using the Kaplan-Meier method and compared among the specialties. Predictors of persistence were estimated using logistic regression with adjustment for covariates. Pearson correlation coefficients were calculated to identify risk associations. RESULTS: A total of 252 subjects were identified. At 12 weeks, 6 months and 1 year, FPMRS patients had the highest persistence rates of 93 %, 87 % and 79 % in contrast to 72 %, 68 % and 50 % in GU patients, and 83 %, 71 % and 63 % in IM patients (p = 0.006, p = 0.007, p = 0.001, respectively). The median persistence in FPMRS patients was 738 days, in GU patients 313 days and in IM patients 486 days (p = 0.006). Of the FPMRS patients, 61 % switched to at least a second medication, as compared to 27 % of IM patients and 14 % of GU patients (p < 0.0001). CONCLUSIONS: Persistence on OAB pharmacotherapy was higher among FPMRS patients than among GU and IM patients in this community setting. These results suggest that persistence is higher under subspecialist supervision.

Squalene hopene cyclases: highly promiscuous and evolvable catalysts for stereoselective CC and CX bond formation.

We review here how the inherent promiscuous nature, as well as the evolvability of terpene cyclase enzymes enables new applications in chemistry. We mainly focus on squalene hopene cyclases, class II triterpene synthases that use a proton-initiated cationic polycyclization cascade to form carbopolycyclic products. We highlight recent findings to demonstrate that these enzymes are capable of activating different functionalities other than the traditional terminal isoprene C=C-group as well as being compatible with a wide range of nucleophiles beyond the 'ene-functionality'. Thus, squalene hopene cyclases demonstrate a great potential to be used as a toolbox for general Brønsted acid catalysis.

Synthesis of heterocyclic terpenoids by promiscuous squalene-hopene cyclases.

PROMISCUOUS ENZYMES: The substrate promiscuity of squalene-hopene cyclases has been explored and applied in the enzyme-catalyzed synthesis of heterocyclic terpenoids. Features of this work include cyclization reactions without pyrophosphate activation, and stereospecific ring closure of substrates of varying chain length and terminal nucleophile. This provides a biocatalytic alternative to traditional chemical catalysts.

Activation-independent cyclization of monoterpenoids.

The biosynthesis of cyclic monoterpenes (C(10)) generally requires the cyclization of an activated linear precursor (geranyldiphosphate) by specific terpene cyclases. Cyclic triterpenes (C(30)), on the other hand, originate from the linear precursor squalene by the action of squalene-hopene cyclases (SHCs) or oxidosqualene cyclases (OSCs). Here, we report a novel terpene cyclase from Zymomonas mobilis (ZMO1548-Shc) with the unique capability to cyclize citronellal to isopulegol. To our knowledge, ZMO1548-Shc is the first biocatalyst with diphosphate-independent monoterpenoid cyclase activity. A combinatorial approach using site-directed mutagenesis and modeling of the active site with a bound substrate revealed that the cyclization of citronellal proceeds via a different mechanism than that of the cyclization of squalene.