Abstract Background Less postoperative pain is typically associated with a minimally invasive hysterectomy compared to a laparotomy approach but poor pain control can still be an issues. Multiple ...guidelines exist for managing postoperative pain yet most are not specialty-specific and are based on procedures bearing little relevance to a minimally invasive hysterectomy. Objective To determine if there is enough quality evidence within the benign gynecology literature to make non-opioid pain control recommendations for women undergoing a benign minimally invasive hysterectomy. Study Design We queried PubMed, ClinicalTrials.gov and Cochrane databases using MeSH terms: “postoperative pain,” “perioperative pain,” “postoperative analgesia,” “pain management,” “pain control,” “minimally invasive gynecologic surgery” and “hysterectomy”. A manual examination of references from identified studies was also performed. All PubMed published studies involving minimally invasive hysterectomies through November 9, 2016 were included. This systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Studies were restricted to benign minimally invasive hysterectomies evaluating non-opioid pharmacologic therapies. Primary outcomes included amount of postoperative analgesics consumed and postoperative pain scores. Two reviewers independently completed an in-depth evaluation of each study for characteristics and results using an Excel database according to inclusion/exclusion criteria. A risk assessment was performed and a quality rating assigned using the Cochrane Collaboration’s Grades of Recommendation, Assessment, Development and Evaluation (GRADE) approach. Results Initially 1,155 studies were identified, 24 met all inclusion criteria. Based on limited data of varying quality, intravenous (IV) acetaminophen, anticonvulsants and dexamethasone demonstrate opioid-sparing benefits while ketorolac shows mixed results in laparoscopic hysterectomies. Paracervical blocks provide pain-reducing benefits in vaginal hysterectomies. Conclusions Convincing conclusions are difficult to draw because of the heterogeneous and contradictory nature of the literature. There is a clear need for more high-quality research evaluating each medication type for post-hysterectomy pain control.
Objective We sought to evaluate candidate mechanisms underlying the pelvic floor dysfunction in women with chronic pelvic pain (CPP) and/or painful bladder syndrome (PBS)/interstitial cystitis. ...Notably, prior studies have not consistently controlled for potential confounding by psychological or anatomical factors. Study Design As part of a larger study on pelvic floor pain dysfunction and bladder pain sensitivity, we compared a measure of mechanical pain sensitivity, pressure pain thresholds (PPTs), between women with pelvic pain and pain-free controls. We also assessed a novel pain measure using degree and duration of postexam pain aftersensation, and conducted structural and functional assessments of the pelvic floor to account for any potential confounding. Phenotypic specificity of pelvic floor measures was assessed with receiver operator characteristic curves adjusted for prevalence. Results A total of 23 women with CPP, 23 women with PBS, and 42 pain-free controls completed the study. Women with CPP or PBS exhibited enhanced pain sensitivity with lower PPTs (1.18 interquartile range, 0.87–1.41 kg/cm2 ) than pain-free participants (1.48 1.11-1.76 kg/cm2 ; P < .001) and prolonged pain aftersensation (3.5 0-9 vs 0 0-1 minutes; P < .001). Although genital hiatus ( P < .01) was wider in women with CPP there were no consistently observed group differences in pelvic floor anatomy, muscle tone, or strength. The combination of PPTs and aftersensation duration correlated with severity of pelvic floor tenderness (R2 , 41-51; P < .01). Even after adjustment for prevalence, the combined metrics discriminated pain-free controls from women with CPP or PBS (area under the curve, 0.87). Conclusion Both experimental assessment of pelvic floor pain thresholds and measurement of sustained pain are independently associated with pelvic pain phenotypes. These findings suggest systematic clinical assessment of the time course of provoked pain symptoms, which occurs over seconds for mechanical pain thresholds vs minutes for aftersensation pain, would be helpful in identifying the fundamental mechanisms of pelvic floor pain. Longitudinal studies of therapies differentially targeting these discrete mechanisms are needed to confirm their clinical significance.
Mitotic yeast cells express five septins (Cdc3, Cdc10, Cdc11, Cdc12, and Shs1/Sep7). Only Shs1 is nonessential. The four essential septins form a complex containing two copies of each, but their ...arrangement was not known. Single-particle analysis by EM confirmed that the heterooligomer is octameric and revealed that the subunits are arrayed in a linear rod. Identity of each subunit was determined by examining complexes lacking a given septin, by antibody decoration, and by fusion to marker proteins (GFP or maltose binding protein). The rod has the order Cdc11-Cdc12-Cdc3-Cdc10-Cdc10-Cdc3-Cdc12-Cdc11 and, hence, lacks polarity. At low ionic strength, rods assemble end-to-end to form filaments but not when Cdc11 is absent or its N terminus is altered. Filaments invariably pair into long parallel "railroad tracks." Lateral association seems to be mediated by heterotetrameric coiled coils between the paired C-terminal extensions of Cdc3 and Cdc12 projecting orthogonally from each filament. Shs1 may be able to replace Cdc11 at the end of the rod. Our findings provide insights into the molecular mechanisms underlying the function and regulation of cellular septin structures.
Background The underlying causes of vulvar pain in women with vulvodynia remain poorly understood. Catechol- O -methyltransferase, an enzyme that metabolizes catecholamines, is a neuromodulator that ...is involved with perception and sensitivity to pain. The catechol- O -methyltransferase gene is polymorphic, and a single nucleotide polymorphism is associated with low activity and heightened pain sensitivity. The variant allele that encodes this polymorphism commonly is called the “L allele” because of its low enzyme activity as opposed to the normal H (high activity) allele. Objective The methionine-containing catechol- O -methyltransferase protein coded by the L allele results in elevated catecholamine levels, reduced inactivation of the dopaminergic and adrenergic systems, and increased sensitivity to pain. This polymorphism not only may decrease the pain threshold in response to acute pain but also may facilitate the development of chronic pain. Therefore, the objective of our study was to assess whether a variation in the catechol- O -methyltransferase genotype is involved in increased pain sensitivity in women with vulvodynia. Study Design We conducted a prospective cohort study. Methods Buccal swabs were collected from 167 white women with vulvodynia and 107 control subjects; the DNA was tested for a single nucleotide polymorphism at position 158 (rs4680) in the catechol- O -methyltransferase gene. Results Women with vulvodynia had a marginally increased, yet not significant, prevalence of the catechol- O -methyltransferase genotype that is associated with high activity of the coded protein: 32.9% in the women with vulvodynia, as opposed to 21.5% in the control subjects (odds ratio, 1.80; 95% confidence interval, 1.02–3.15). Subgrouping the cases based on pain frequency revealed that the elevated occurrence of this catechol- O -methyltransferase genotype was present in 40.6% of the subset of women who experienced pain only with sexual intercourse vs only 21.5% of control subjects (odds ratio, 2.50; 95% confidence interval, 1.27–4.93). Also, women with primary vulvodynia had a significantly higher prevalence of the H allele than did the control subjects (62.9% vs 48.1%; odds ratio, 1.82; 95% confidence interval, 1.05–3.17). Conclusion Increased pain sensitivity in women with vulvodynia is not due to a genetically determined low catechol- O -methyltransferase enzyme activity. Other mechanisms may account for alterations in catechol- O -methyltransferase activity in women with pain that is limited to intercourse or primary vulvodynia that contributes to pain sensitivity.
Our objective was to assess the sensitivity and specificity of human papillomavirus (HPV) testing for cervical cancer screening in randomized trials. We conducted a systematic literature search of ...the following databases: MEDLINE, CINAHL, EMBASE, and Cochrane. Eligible studies were randomized trials comparing HPV-based to cytology-based screening strategies, with disease status determined by colposcopy/biopsy for participants with positive results. Disease rates (cervical intraepithelial neoplasia CIN2 or greater and CIN3 or greater), sensitivity, and positive predictive value were abstracted or calculated from the articles. Six studies met inclusion criteria. Relative sensitivities for detecting CIN3 or greater of HPV testing-based strategies vs cytology ranged from 0.8 to 2.1. The main limitation of our study was that testing methodologies and screening/management protocols were highly variable across studies. Screening strategies in which a single initial HPV-positive test led to colposcopy were more sensitive than cytology but resulted in higher colposcopy rates. These results have implications for cotesting with HPV and cytology as recommended in the United States.
To evaluate if preincision infiltration with extended-release liposomal bupivacaine provides improved overall pain relief compared with 0.25% bupivacaine after laparoscopic or robotic-assisted ...hysterectomy.
A single-center double-masked randomized controlled trial (Canadian Task Force Classification I).
A tertiary-care community hospital.
Patients recruited from July 2015 through January 2016. Sixty-four patients were randomized, and 59 were analyzed for the primary outcome.
Women scheduled to undergo multiport laparoscopic or robotic-assisted total hysterectomy for benign indications were randomized to receive preincision infiltration with undiluted liposomal bupivacaine or 0.25% bupivacaine.
The primary outcome was overall average pain intensity by numeric rating scale (0-10) using the Brief Pain Inventory (BPI) via telephone survey on postoperative day (POD) 3. A sample size of 28 per group (N = 56) was planned to detect a 30% change in pain scores. Secondary outcomes were overall average and worst numeric pain scores on PODs 1, 2, and 14; pain scores in hospital; BPI pain interference scores; and total opioid use. There were no demographic differences between the 2 groups. For the primary outcome, we found a decrease in the average (p = .02) pain scores on POD 3 in the liposomal bupivacaine group. We also found a decrease in worst pain scores on POD 2 (p = .03) and POD 3 (p = .01). There were no differences in pain scores while in the hospital or on POD 1 or POD 14. There were no differences in BPI pain interference scores, opioid use, or reported adverse effects.
For laparoscopic and robotic-assisted multiport hysterectomies, there is evidence of decreased average postoperative pain with liposomal bupivacaine compared with 0.25% bupivacaine for port-site analgesia on POD 3, but no difference in opioid use or measures of functioning.
The use of porcine cells and organs as a source of xenografts for human patients would vastly increase the donor pool; however, both humans and Old World primates vigorously reject pig tissues due to ...xenoantibodies that react with the polysaccharide galactose alpha (1,3) galactose (alphaGal) present on the surface of many porcine cells. We previously examined the xenoantibody response in patients exposed to porcine hepatocytes via treatment(s) with bioartficial liver devices (BALs), composed of porcine cells in a support matrix. We determined that xenoantibodies in BAL-treated patients are predominantly directed at porcine alphaGal carbohydrate epitopes, and are encoded by a small number of germline heavy chain variable region (VH) immunoglobulin genes. The studies described in this manuscript were designed to identify whether the xenoantibody responses and the IgVH genes encoding antibodies to porcine hepatocytes in non-human primates used as preclinical models are similar to those in humans. Adult non-immunosuppressed rhesus monkeys (Macaca mulatta) were injected intra-portally with porcine hepatocytes or heterotopically transplanted with a porcine liver lobe. Peripheral blood leukocytes and serum were obtained prior to and at multiple time points after exposure, and the immune response was characterized, using ELISA to evaluate the levels and specificities of circulating xenoantibodies, and the production of cDNA libraries to determine the genes used by B cells to encode those antibodies.
Xenoantibodies produced following exposure to isolated hepatocytes and solid organ liver grafts were predominantly encoded by genes in the VH3 family, with a minor contribution from the VH4 family. Immunoglobulin heavy-chain gene (VH) cDNA library screening and gene sequencing of IgM libraries identified the genes as most closely-related to the IGHV3-11 and IGHV4-59 germline progenitors. One of the genes most similar to IGHV3-11, VH3-11cyno, has not been previously identified, and encodes xenoantibodies at later time points post-transplant. Sequencing of IgG clones revealed increased usage of the monkey germline progenitor most similar to human IGHV3-11 and the onset of mutations.
The small number of IGVH genes encoding xenoantibodies to porcine hepatocytes in non-human primates and humans is highly conserved. Rhesus monkeys are an appropriate preclinical model for testing novel reagents such as those developed using structure-based drug design to target and deplete antibodies to porcine xenografts.
Objective:
The primary objective of this study is to assess whether the degree of religiosity or certain moral teachings are associated with dyspareunia.
Methods:
A cross-sectional survey with 24 ...questions was designed that incorporated the previously validated Duke Religiosity Index questionnaire, medical and sexual history, and demographic information. The index measures organizational, non-organizational, and intrinsic religiosity. Participants were recruited from Ob/Gyn and Family Medicine clinics and from a large university in our community.
Results:
A total of 901 surveys were included in final analysis. Among our study population, the prevalence of dyspareunia was 19.4%. Participants were categorized by the presence or absence of the primary outcome, dyspareunia. There were no differences in the scores of organized religiosity, p = 0.73 (2.98 ± 0.47 vs 3.04 ± 1.55), non-organized religiosity, p = 0.57 (2.62 ± 1.71 vs 2.82 ± 1.82), or intrinsic religiosity p = 0.64 (10.53 ± 3.63 vs 10.47 ± 4.06) in women with and without dyspareunia, respectively. No associations were found between dyspareunia and a participant’s current or childhood religious affiliation. However, women who were taught “sex is bad” while growing up had a higher rate of dyspareunia compared to those who were not taught this belief, (27.0% vs 15.3%, p < 0.001). Similar results were found in women who were taught to “wait until marriage to have sex”; 21.6% experienced dyspareunia while only 13.2% of those who were not taught to wait experienced dyspareunia (p = 0.005).
Conclusions:
While degree of religiosity was not shown to be associated with dyspareunia, women who learned certain restrictive sexual values were at higher risk of experiencing painful intercourse.
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