Uterus-Sparing Surgery: Outcomes of Transvaginal Uterosacral Ligament Hysteropexy.

STUDY OBJECTIVE: Recently, there has been a paradigm shift toward uterine conservation during the surgical management of pelvic organ prolapse (POP), specifically uterine prolapse. There are few reports on transvaginal uterosacral ligament hysteropexy (TULH). This study aimed to describe our surgical technique and outcomes. DESIGN: Retrospective review and description of surgical technique. Anatomic outcome has been reported using the POP quantification system. Complications were segregated. A comparison of parametric continuous variables was performed using paired t test. Categoric variables were evaluated using the Pearson χ2 test and the Fisher exact test. A p-value <.05 was considered significant. SETTING: Teaching hospital. PATIENTS: Forty patients who underwent TULH from 2009 to 2017. INTERVENTIONS: TULH. MEASUREMENTS AND MAIN RESULTS: A total of 40 patients met the inclusion criteria. Of these, 56.1% had preoperative stage 3 prolapse. The median operative time was 116 minutes. The mean estimated blood loss was 158.5 mL. Transient ureteral obstruction occurred in 2 patients. The mean follow-up time was 17.2 months, and all patients had significant improvement of prolapse (p <.001). There was also an improvement in urinary incontinence and bladder storage symptoms (p <.001). None of the patients were reoperated on for recurrent POP. CONCLUSION: TULH is an effective uterus-preserving surgical alternative for the treatment of uterovaginal prolapse and provides good apical support. It is also associated with a low short-term recurrence and incidence of reoperation. TULH is a viable option for suitable patients with uterovaginal prolapse who desire uterine conservation.

Site Selective Antibody-Oligonucleotide Conjugation via Microbial Transglutaminase.

Nucleic Acid Therapeutics (NATs), including siRNAs and AntiSense Oligonucleotides (ASOs), have great potential to drug the undruggable genome. Targeting siRNAs and ASOs to specific cell types of interest has driven dramatic improvement in efficacy and reduction in toxicity. Indeed, conjugation of tris-GalNAc to siRNAs and ASOs has shown clinical efficacy in targeting diseases driven by liver hepatocytes. However, targeting non-hepatic diseases with oligonucleotide therapeutics has remained problematic for several reasons, including targeting specific cell types and endosomal escape. Monoclonal antibody (mAb) targeting of siRNAs and ASOs has the potential to deliver these drugs to a variety of specific cell and tissue types. However, most conjugation strategies rely on random chemical conjugation through lysine or cysteine residues resulting in conjugate heterogeneity and a distribution of Drug:Antibody Ratios (DAR). To produce homogeneous DAR-2 conjugates with two siRNAs per mAb, we developed a novel two-step conjugation procedure involving microbial transglutaminase (MTGase) tagging of the antibody C-terminus with an azide-functionalized linker peptide that can be subsequently conjugated to dibenzylcyclooctyne (DBCO) bearing oligonucleotides through azide-alkyne cycloaddition. Antibody-siRNA (and ASO) conjugates (ARCs) produced using this strategy are soluble, chemically defined targeted oligonucleotide therapeutics that have the potential to greatly increase the number of targetable cell types.

Total vaginectomy and urethral lengthening at time of neourethral prelamination in transgender men.

INTRODUCTION AND HYPOTHESIS: For transgender men (TGM), gender-affirmation surgery (GAS) is often the final stage of their gender transition. GAS involves creating a neophallus, typically using tissue remote from the genital region, such as radial forearm free-flap phalloplasty. Essential to this process is vaginectomy. Complexity of vaginal fascial attachments, atrophy due to testosterone use, and need to preserve integrity of the vaginal epithelium for tissue rearrangement add to the intricacy of the procedure during GAS. We designed the technique presented here to minimize complications and contribute to overall success of the phalloplasty procedure. METHODS: After obtaining approval from the Institutional Review Board, our transgender (TG) database at the University of Miami Hospital was reviewed to identify cases with vaginectomy and urethral elongation performed at the time of radial forearm free-flap phalloplasty prelamination. Surgical technique for posterior vaginectomy and anterior vaginal wall-flap harvest with subsequent urethral lengthening is detailed. RESULTS: Six patients underwent total vaginectomy and urethral elongation at the time of radial forearm free-flap phalloplasty prelamination. Mean estimated blood loss (EBL) was 290 ± 199.4 ml for the vaginectomy and urethral elongation, and no one required transfusion. There were no intraoperative complications (cystotomy, ureteral obstruction, enterotomy, proctotomy, or neurological injury). One patient had a urologic complication (urethral stricture) in the neobulbar urethra. CONCLUSIONS: Total vaginectomy and urethral lengthening procedures at the time of GAS are relatively safe procedures, and using the described technique provides excellent tissue for urethral prelamination and a low complication rate in both the short and long term.

Evaluation and surgery for stress urinary incontinence: A FIGO working group report.

AIMS: To review available evidence regarding evaluation and treatment of stress urinary incontinence (SUI) and provide recommendations for management of urinary incontinence under specific conditions determined by the International Federation of Gynecology and Obstetrics (FIGO) Working Group. METHODS: The FIGO Working Group discussed the management of SUI during meetings and assessed the evidence. The search of evidence was performed using MEDLINE® and Cochrane databases as well as additional searches from societies and major organizations for additional guidelines and recommendations and hand searches from bibliographies. Initial searches from 1985 to December 31, 2012 extended until July 15, 2015. After review, recommendations are made based on levels of evidence according to the recommendations from Oxford EBM Center. RESULTS: Initial evaluation of SUI consists of history and physical examination; cough stress test, evaluation for urinary tract infections (UTI), assessment of urethral mobility, and post-void residual volumes (LOE 5). Urodynamic studies are not necessary to evaluate patients with uncomplicated SUI (LOE 1a). Conservative treatment should be tried prior to surgery and more importantly in areas of low resources (LOE 5). Midurethral slings (MUS), pubovaginal (traditional suburethral) slings (PVS), and Burch colposuspension are effective in treating SUI (LOE 1a). Patients with SUI with ISD or UUI appear to have lower cure rates than patients without (LOE 2-4). There are limited data on surgical outcomes under limited resources (LOE 5). CONCLUSIONS: MUS, PVS, and Burch colposuspension are effective treatments for SUI. Evidence for recommendations to treat patients in underserved low resource areas is lacking. Neurourol. Urodynam. 36:518-528, 2017. © 2016 Wiley Periodicals, Inc.

MACULAR HOLE AFTER PARS PLANA VITRECTOMY FOR RHEGMATOGENOUS RETINAL DETACHMENT.

PURPOSE: To report the clinical features, possible associations and treatment outcomes of patients with macular hole after pars plana vitrectomy (PPV) (single or multiple) for rhegmatogenous retinal detachment (RD). METHODS: Retrospective consecutive case series from July 2009 to July 2014. RESULTS: In the 15 study patients, the average time from RD surgery to macular hole diagnosis was 119 days (range: 41-398 months). Possible associations include epiretinal membrane (73%, 11/15 patients), macula-off RD (60%, 9/15 patients), recurrent RD (47%, 7/15 patients), and high myopia (56%, 5/9 patients). Single surgery was successful in hole closure in 8/15 patients (Group A) while 7/15 patients underwent multiple surgeries (Group B). Macular hole closure was achieved in 7/8 (87.5%) patients in Group A compared to 4/7 (57.1%) patients in Group B. Improvement of at least two lines of Snellen's visual acuity was achieved in 4/8 (50.0%) and 4/7 (57.1%) patients in Group A and B, respectively. CONCLUSION: In patients with macular hole formation after pars plana vitrectomy for RD, possible associations were epiretinal membrane, macula-off RD, recurrent RD, and high myopia. Even when macular hole closure was achieved, limited visual improvement occurred.

Diagnostic Cytologic Features of Uveal Melanoma.

PURPOSE: To report the cytologic characteristics of uveal melanoma. DESIGN: This is a prospective, single-center study of consecutive patients. SUBJECTS: All patients with a clinical diagnosis of uveal melanoma from May 2009 to July 2013 who underwent prognostication fine-needle aspiration biopsy (FNAB) were included. METHODS: The cytologic characteristics of uveal melanoma were analyzed for 150 consecutive patients with a clinical diagnosis of uveal melanoma who were treated at the Cleveland Clinic Cole Eye Institute between May 2009 and August 2012. MAIN OUTCOME MEASURES: Cellular features of all cases were analyzed for cell type, presence of melanin, nuclear grade, tumor-infiltrating lymphocytes, and necrosis. Cytology was then correlated with histopathology in enucleated eyes. RESULTS: A total of 150 patients were included. Seven samples of tumor resections were excluded from the study because they were studied by impression smears. A total of 143 FNAB samples of 143 patients formed the basis for analysis. Fifty-three percent of the patients were male, and the average age for all patients was 60 years. Transcorneal (n = 8), transscleral (n = 71), and transvitreal (n = 64) approaches were used. Of 143 samples, 131 were adequate. Among these, spindle cells were observed in 98% (63% mixed and 35% spindle only), whereas only epithelioid cells were observed in 2 samples. Melanin granules were observed in 80% of samples. Tumor nuclear grade (atypia) increased with tumor height and by tumor location (least atypia with iris tumors). CONCLUSIONS: Cytologic features such as spindle cells and melanin granules, present in 98% and 80% of samples, respectively, are important cytologic diagnostic features. Tumor nuclear grade (atypia) increased with tumor height. Iris melanoma has bland features compared with ciliary and choroidal melanoma.

28-day intraocular pressure reduction with a single dose of brimonidine tartrate-loaded microspheres.

Treatment of glaucoma by intraocular pressure (IOP) reduction is typically accomplished through the administration of eye drops, the difficult and frequent nature of which contributes to extremely low adherence rates. Poor adherence to topical treatment regimens in glaucoma patients can lead to irreversible vision loss and increased treatment costs. Currently there are no approved treatments for glaucoma that address the inherent inefficiencies in drug delivery and patient adherence. Brimonidine tartrate (BT), a common glaucoma medication, requires dosing every 8-12 h, with up to 97% of patients not taking it as prescribed. This study provides proof-of-principle testing of a controlled release BT formulation. BT was encapsulated in poly(lactic-co-glycolic) acid microspheres and drug release was quantified using UV-Vis spectroscopy. For in vivo studies, rabbits were randomized to receive a single subconjunctival injection of blank (no drug) or BT-loaded microspheres or twice daily topical 0.2% BT drops. The microspheres released an average of 2.1 ± 0.37 µg BT/mg microspheres/day in vitro. In vivo, the percent decrease in IOP from baseline was significantly greater in the treated eye for both topical drug and drug-loaded microspheres versus blank microspheres throughout the 4-week study, with no evidence of migration or foreign body response. IOP measurements in the contralateral, untreated eyes also suggested a highly localized effect from the experimental treatment. A treatment designed using the release systems described in this study would represent a vast improvement over the current clinical standard of 56-84 topical doses over 28 days.

Orbital and intraocular myofibroblastoma.

A 66-year-old woman presented with a blind, painful, hypertensive, and proptotic left eye. Computed tomographic imaging revealed a well-circumscribed mass involving the left orbit and globe. Metastatic work-up failed to reveal extraorbital lesions and the tumor was removed in toto via an evisceration approach orbitotomy. Histopathology and immunohistochemistry were most consistent with mammary-type myofibroblastoma with fascicles of bland, uniform spindle cells that stained positive for desmin and CD34. We are not aware of previous reports of orbital or ocular myofibroblastoma. This neoplasm has not been shown to recur, undergo malignant transformation, or metastasize. Familiarity with its clinical, histopathologic, and immunohistochemical features may improve diagnostic accuracy and treatment decisions for patients presenting with similar findings.

What are the Andean Colombian anurans? Empirical regionalization proposals vs. observed patterns of compositional dissimilarity.

Background: Defining Andean anurans through their altitudinal limits has been a common practice in species lists, studies of responses to climate change among others, especially in the northern Andes. At least three proposals to differentiate Andean anurans from lowland anurans through elevation and at least one to differentiate Andean anurans from high mountain anurans have been formulated. However, the most frequently used altitudinal limits are not based on theoretical or numerical support, but on observations or practical definitions. Additionally, these proposals have been applied equally to different portions of the Andes, ignoring the fact that even between slopes of the same mountain, environmental conditions (and therefore the distribution of species) may differ. The objective of this work was to evaluate the concordance between the altitudinal distribution of anurans in the Colombian Andes and four different altitudinal delimitation proposals. Methods: We constructed our study area in a manner that allowed us to include species from the Andean region (as traditionally defined) and adjacent lowlands, because if the boundaries criteria were applied they would separate the species of the latter by themselves. We divided the study area into eight entities according to the watershed and the course of the most important rivers. We conducted a bibliographic search for all anurans in the cordilleras and inter-Andean valleys of Colombia and complemented the search with information on anurans for the region available in the GBIF. After curing the species distribution points, we generated elevation bands of 200 m amplitude for both the study area and for each Andean entity. Subsequently, we performed a cluster analysis to evaluate the grouping of the elevation bands according to their species composition. Results: In none of the cases (neither for the entire study area nor for any of the entities) we found a correspondence of any of the traditionally used boundaries and the altitudinal distribution of Anurans in the Andean region of Colombia. Instead, on average, the altitudinal delimitation proposals arbitrarily spanned the altitudinal distribution of about one third of the species distributed in the study area. Conclusions: We suggest that, although, based on our results, some Andean entities can be divided according to the altitudinal composition of the species that occur in them, we did not find any results that support the idea of a generalizable altitudinal limit for the Colombian Andes. Thus, to avoid biases in studies that may later be used by decision makers, the selection of anuran species in studies in the Colombian Andes should be based on biogeographic, phylogenetic or natural history criteria and not on altitudinal limits as they have been used.

Do habitat fragmentation and degradation influence the strength of fine-scale spatial genetic structure in plants? A global meta-analysis.

As primarily sessile organisms, plants often show a non-random spatial distribution of genotypes over distance. This process known as fine-scale spatial genetic structure (FSGS) has been suggested through systematic reviews to depend on life form, mating system, and pollen and seed dispersal vectors, while there is no consensus on its behaviour due to external factors, such as anthropogenic habitat changes. By conducting a systematic review and global meta-analysis of empirical FSGS studies, we aimed to evaluate how anthropogenic habitat fragmentation and degradation influence the strength of FSGS in plant populations by means of the Sp statistic. Moreover, we tested how pollination and seed dispersal vectors contribute to the variation of the Sp statistic. We retrieved 243 FSGS studies from 1960 to 2020 of which only 65 were informative for the systematic review. Most empirical studies comprised outcrossers (84%) and trees (67%), with few herbs (23%) and scarce annual species (2%). In weighted meta-analyses for 116 plant populations (31 studies), we did not detect significant effects in the magnitude of effect sizes for the Sp statistic among undisturbed, degraded and fragmented habitats. Results showed significant effects for seed dispersal vectors, but not for pollination. Overall, we observed high variation among the effect sizes (not related to the goodness-of-fit of mixed models) of habitat status, pollination and seed dispersal categories, which precludes identifying biological trends on the Sp statistic. More empirical studies are needed that contrast multiple plant populations in disturbed versus undisturbed habitats, and by increasing the taxonomic groups, such as herbs and annual plants.

Xicotli Data: a project to retrieve plant-bee interactions from citizen science.

Background: Xicotli data is the short name given to the dataset generated within the project framework "Integration of Biodiversity Data for the Management and Conservation of Wild Bee-Plant Interactions in Mexico (2021-2023)", as xicotli is the generic word for a bee in Nahuatl. The team comprised eco-informaticians, ecologists and taxonomists of both native bees and flora. The generated dataset contains so far 4,532 curated records of the plants, which are potential hosts of species of three focal families of bees native to Mexico: Apidae, Halictidae and Megachilidae and morphological and ecological data of the plant-bee interactions. This dataset was integrated and mobilised from citizen observations available at naturalista.mx (iNat), which were compiled through the iNaturalist project. New information: The new information obtained with the Xicotli data project was: Taxonomic information about bee species curated by taxonomists based on the information contained in iNaturalist;Taxonomic identification of the host plants by a botanist from the photos compiled by the Xicotli Data project;Data on the ecomorphological traits of bees and plants based on expert knowledge and literature. All the data were integrated into the Xicotli Data Project via the creation of new "observation fields". The visibility of the information originally contained in iNaturalist was maximized and can be consulted directly on the iNaturalist platform.

Effects of PPAR-delta agonist and zinc on vaginal smooth muscle cells collagen and tropoelastin production.

INTRODUCTION AND HYPOTHESIS: The objective was to measure the effects of peroxisome proliferator-activated receptor delta (PPAR-delta) agonist and zinc sulfate (ZS) on vaginal smooth muscle cell (SMC) proliferation, tropoelastin production, and collagen production. METHODS: SMC cultures were performed from vaginal wall biopsies and were incubated with ZS and PPAR-delta agonist GW501516 (GW). Cell proliferation was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Supernatants and cell lysates were collected. Tropoelastin production was measured by Fastin Elastin Assay and collagen was measured with Sircol Collagen Assay. RESULTS: SMC proliferation was similar with 20 µM ZS or 10 nM GW compared to control. Tropoelastin production was significantly increased by 20 µM ZS and by 10 nM GW. Cell culture surface deposited elastin production was significantly increased by 20 µM ZS and by the combination of 20 µM ZS with 10 nM GW, and collagen production was significantly increased by 10 nM GW and by the combination of 20 µM ZS with 10 nM GW. CONCLUSIONS: PPAR-delta agonist and ZS increases vaginal SMC tropoelastin and collagen production.

Estrogen inhibits vaginal tropoelastin and TGF-ß1 production.

INTRODUCTION AND HYPOTHESIS: The aim of this study was to quantify the effects of estrogen on vaginal smooth muscle cell (SMC) tropoelastin and transforming growth factor (TGF)-ß1 production. METHODS: Primary SMC were incubated with estradiol, and cell proliferation was assessed by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) assay at 48 h. Supernatants were collected and tropoelastin and TGF-ß1 levels measured. RESULTS: SMC proliferation was significantly increased by estradiol [relative cell number, mean ± standard error (SE), estradiol 0.1 µM 116 ± 19 % of control (P = NS), 1 µM 127 ± 13 % of control (P < 0.05), 10 µM 153 ± 26 % of control, (P < 0.05)]. Tropoelastin production was significantly decreased by estrogen [mean ± SE, estradiol 0.1 µM 78 ± 2 % of control (P < 0.05), 1 µM 76 ± 4 % of control (P < 0.05), 10 µM 67 ± 3 % of control, (P < 0.05)]. In addition, TGF-ß1 production was significantly decreased [mean ± SE, estradiol 0.1 µM 96 ± 4 % of control (P = NS), 1 µM 84 ± 6 % of control (P < 0.05), 10 µM 70 ± 6 % of control, (P < 0.05)]. CONCLUSION: Estrogen increases vaginal SMC proliferation and inhibits tropoelastin and TGF-ß1 production.

TGF-beta 1 is a potential regulator of vaginal tropoelastin production.

INTRODUCTION AND HYPOTHESIS: Our aims were to correlate transforming growth factor (TGF)-ß1 and elastin mRNA expression in the vagina of women and to measure the effects of TGF-ß1 on vaginal smooth muscle cell (SMC) proliferation and tropoelastin production. METHODS: Vaginal walls were sampled in women (n = 20). TGF-ß1 and elastin mRNA expression was assessed by RT-PCR. SMC cultures were performed from vaginal wall biopsies. SMC were incubated with TGF-ß1, and cell proliferation was assessed by MTT-assay. Tropoelastin production was measured by the Fastin Elastin Assay. RESULTS: There was a significant positive correlation between TGF-ß1 and elastin mRNA (r = 0.784, P < 0.01). SMC proliferation was significantly increased by 10 ng/mL TGF-ß1 [relative cell number, mean ± SD, 198% ± 32% of control (P = 0.01)]. Tropoelastin production was significantly increased by TGF-ß1 [mean ± SD, 645% ± 180% of control (P = 0.01)]. CONCLUSIONS: There is a positive correlation between TGF-ß1 and elastin mRNA expression in the vaginal wall. In vitro, TGF-ß1 increases vaginal tropoelastin production in vaginal SMC.

Enlargement of the genital hiatus is associated with prolapse recurrence in patients undergoing sacrospinous ligament fixation.

OBJECTIVE: To correlate genital hiatus (GH) size with surgical failures in patients undergoing sacrospinous ligament fixation (SSLF) and compare anatomic outcomes after classification based on GH size. METHODS: A retrospective review of 81 patients who underwent SSLF for apical prolapse from 2010 to 2016 at a teaching hospital. Anatomical outcome is reported using the Pelvic Organ Prolapse Quantifications System. A comparison of parametric continuous variables was performed using unpaired Student t test. Categorical variables were evaluated using Pearson's χ2 test and Fisher's exact test. A P value <0.05 was considered significant. RESULTS: Among the 81 patients, no difference in age, parity, body mass index, preoperative prolapse stage or follow-up time was noted between those whose surgery succeeded and those with failed surgery. Postoperatively, a widened GH was significantly associated with recurrent prolapse (P < 0.001). When the preoperative size of the GH was dichotomized into widened (≥4 cm) or normal (<4 cm), there was a non-significant (P = 0.444) trend of more failures in the widened GH group. A posterior colporrhaphy did not improve success. CONCLUSION: Both preoperative and postoperative widened GH correlated with having more surgical failures following SSLF. Importantly, postoperatively a normal size GH was significantly associated with more surgical success.

The effect of biological and synthetic meshes on vaginal smooth muscle cell proliferation.

AIMS: To compare the effects of polypropylene mesh or porcine dermal acellular collagen matrix mesh with and without estradiol supplementation on vaginal smooth muscle cells (VaSMC) proliferation. RESULTS: Under in vitro culture conditions, VaSMC proliferation was significantly higher in the porcine dermal acellular collagen matrix mesh exposed cells compared to the type I polypropylene mesh exposed cells (relative cell number, mean ± SD, 0.27 ± 0.03 vs. 0.21 ± 0.01, P = 0.03). Under estradiol supplementation cell proliferation in the porcine mesh exposed cells remained significantly higher compared to the polypropylene mesh exposed cells (relative cell number, mean ± SD, 0.27 ± 0.04 vs. 0.15 ± 0.03, P < 0.01). CONCLUSION: The decreased rate of erosion found with the utilization of biological absorbable mesh in vaginal reconstructive surgery may partially be explained by the significantly increased VaSMC proliferation with porcine dermal acellular collagen mesh compared to polypropylene mesh.

Cellular proliferation in female pelvic organ prolapse: a pilot study.

PURPOSE: To assess cell proliferation in pelvic organ prolapse (POP). METHODS: Tissue samples of the anterior vaginal wall and uterosacral ligaments (USLs) were obtained from eight women with combined anterior vaginal wall and uterine prolapse and from eight women without POP in a standardized fashion. Immunohistochemistry against Ki-67 was used to assess cell proliferation in vaginal and USL biopsies. RESULTS: There were no significant differences in age, parity, menopausal status or hormone replacement therapy between the two groups. The POP-Q stage of uterine and anterior vaginal wall prolapse was significantly higher in the group of women with prolapse compared to the group without prolapse [median (range) 3 (3-4) vs. 0 (0), <0.01]. There was no significant difference between Ki-67 expressions in women with or without prolapse. CONCLUSION: There were no significant differences in cell proliferation between samples from women with or without POP.

RETINOCYTOMA WITH VITREOUS SEEDING: NEW INSIGHTS FROM ENHANCED DEPTH IMAGING OPTICAL COHERENCE TOMOGRAPHY AND HIGH-RESOLUTION POSTERIOR SEGMENT ULTRASONOGRAPHY.

PURPOSE: To report an atypical case of a patient with symptomatic retinocytoma associated with diffuse calcified vitreous seeds. METHODS: Retrospective chart review. RESULTS: A 46-year-old healthy woman presented with a history of floaters in the right eye for several months. She had been referred for abnormal findings in the retina and vitreous on routine examination. Visual acuity was 20/20. An incidental retinocytoma associated with extensive calcified vitreous seeding was observed. Enhanced depth optical coherence tomography showed an absence of normal retinal layers with numerous cystoid cavities throughout the lesion. High-resolution 20-MHz posterior B-scan ultrasonography demonstrated that the calcified vitreous seeds emanated from the peaked portion of the retinal tumor. CONCLUSION: Calcified vitreous seeding is a rare finding associated with retinocytomas. Enhanced depth imaging optical coherence tomography and high-resolution B-scan ultrasonography may be useful tools in the diagnosis of this uncommon retinal tumor.