A DNA methylation atlas of normal human cell types.

DNA methylation is a fundamental epigenetic mark that governs gene expression and chromatin organization, thus providing a window into cellular identity and developmental processes1. Current datasets typically include only a fraction of methylation sites and are often based either on cell lines that underwent massive changes in culture or on tissues containing unspecified mixtures of cells2-5. Here we describe a human methylome atlas, based on deep whole-genome bisulfite sequencing, allowing fragment-level analysis across thousands of unique markers for 39 cell types sorted from 205 healthy tissue samples. Replicates of the same cell type are more than 99.5% identical, demonstrating the robustness of cell identity programmes to environmental perturbation. Unsupervised clustering of the atlas recapitulates key elements of tissue ontogeny and identifies methylation patterns retained since embryonic development. Loci uniquely unmethylated in an individual cell type often reside in transcriptional enhancers and contain DNA binding sites for tissue-specific transcriptional regulators. Uniquely hypermethylated loci are rare and are enriched for CpG islands, Polycomb targets and CTCF binding sites, suggesting a new role in shaping cell-type-specific chromatin looping. The atlas provides an essential resource for study of gene regulation and disease-associated genetic variants, and a wealth of potential tissue-specific biomarkers for use in liquid biopsies.

Factors Associated with Obstetric Anal Sphincter Injury During Vacuum-Assisted Vaginal Delivery.

INTRODUCTION AND HYPOTHESIS: Obstetric anal sphincter injury (OASI) is a major complication associated with vacuum-assisted vaginal delivery (VAVD). The aim of this study was to evaluate risk factors related to vacuum extraction that are associated with OASI. METHODS: This was a case-control study performed at a tertiary university teaching hospital. Included were patients aged 18-45 years who had a singleton pregnancy resulting in a live, term, VAVD. The study group consisted of women diagnosed with OASI following vacuum extraction. The control group included women following VAVD without OASI. Matching at a ratio of 1:2 was performed. Groups were compared regarding demographic, obstetric. and labor-related parameters, specifically focusing on variables related to the vacuum procedure itself. RESULTS: One hundred and ten patients within the study group and 212 within the control group were included in the final analysis. Patients in the OASI group were more likely to undergo induction of labor, use of oxytocin during labor, increased second stage of labor, higher likelihood of the operator being a resident, increased number of pulls, procedure lasting under 10 min, occipito-posterior head position at vacuum initiation, episiotomy, increased neonatal head circumference, and birthweight. Multivariate logistic regression analysis revealed that increased week of gestation (OR 1.67, 95% CI 1.25-2.22, p < 0.001), unsupervised resident performing the procedure (OR 4.63, 95% CI 2.17-9.90), p < 0.001), indication of VAVD being fetal distress (OR 2.72, 95% CI 1.04-7.10, p = 0.041), and length of procedure under 10 min (OR 4.75, 95% CI 1.53-14.68, p = 0.007) were associated with OASI. Increased maternal age was associated with lower risk of OASI (OR 0.9, 95% CI 0.84-0.98, p = 0.012). CONCLUSIONS: When performing VAVD, increased week of gestation, unsupervised resident performing the procedure, fetal distress as vacuum indication, and vacuum procedure under 10 min were associated with OASI. In contrast, increased maternal age was shown to be a protective factor.

Transplantation of Mesenchymal Stem Cells Derived from Old Rats Improves Healing and Biomechanical Properties of Vaginal Tissue Following Surgical Incision in Aged Rats.

Pelvic floor dysfunction encompasses a group of disorders that negatively affect the quality of women's lives. These include pelvic organ prolapse (POP), urinary incontinence, and sexual dysfunction. The greatest risk factors for prolapse are increased parity and older age, with the largest group requiring surgical intervention being post-menopausal women over 65. Prolapse recurrence rates following surgery were reported to be as high as 30%. This may be attributed to ineffective healing in the elderly. Autologous stem cell transplantation during surgery may improve surgical results. In our previous studies, we showed that the transplantation of bone marrow-derived mesenchymal stem cells (MSCs) from young donor rats improved the healing of full-thickness vaginal surgical incision in the vaginal wall of old rats, demonstrated by both histological and functional analysis. In order to translate these results into the clinical reality of autologous MSC transplantation in elderly women, we sought to study whether stem cells derived from old donor animals would provide the same effect. In this study, we demonstrate that MSC transplantation attenuated the inflammatory response, increased angiogenesis, and exhibited a time-dependent impact on MMP9 localization. Most importantly, transplantation improved the restoration of the biomechanical properties of the vagina, resulting in stronger healed vaginal tissue. These results may pave the way for further translational studies focusing on the potential clinical autologous adjuvant transplantation of MSCs for POP repair for the improvement of surgical outcomes.

Surgical outcomes in patients aged 70 years and older following uterosacral ligament suspension: a comparative study.

PURPOSE: The number of elderly patients bothered by pelvic organ prolapse symptoms is growing rapidly. The aim of this study was to evaluate the relationship between age and surgical outcomes in women undergoing uterosacral ligament suspension for treatment of apical prolapse. METHODS: We performed a retrospective cohort study including women who underwent uterosacral ligament suspension between 2010 and 2020. The cohort was divided into two groups: (1) Patients 70 years or older; (2) Patients under the age of 70. Outcome measures included clinical, anatomical, and composite outcomes as well as patient satisfaction. RESULTS: A total of 271 patients were included in the final analysis. Of them 209 patients were under age 70 and 62 patients 70 years or older. Mean age was 59 ± 6 vs. 73 ± 3 for the young and elderly age groups, respectively. Clinical success was high for both groups, reaching 94% vs. 89% for elderly and young patients, respectively (p = 0.34). Anatomical and composite outcome success were higher in the young age group (76% vs. 56%, p < 0.01 and 70% vs. 54%, p = 0.02, respectively); however, following multivariate analysis these differences were no longer statistically significant. Following multivariate logistic regression analysis for the dependent parameter of anatomical success, increased pre-operative genital hiatus and vaginal surgical route were associated with anatomical failure while performing a concomitant posterior colporrhaphy increased likelihood for anatomical success. CONCLUSION: Women over the age of 70 undergoing uterosacral ligament suspension for treatment of apical prolapse have comparable outcomes to younger patients.

Birthweight difference between deliveries and the risk of obstetric anal sphincter injury in parous women.

INTRODUCTION AND HYPOTHESIS: While obstetric anal sphincter injury (OASI) is less frequent in parous compared to nulliparous women, it remains a major concern affecting quality of life of women worldwide. The aim of this study was to evaluate the association between birthweight (BW) difference between deliveries and risk of OASI in parous women. METHODS: We performed a retrospective case-control study including parous women with at least one previous vaginal delivery who were diagnosed with OASI. The control group consisted of parous women who did not have OASI during vaginal delivery. Controls were matched in a 1:2 ratio by year of birth, maternal age, and parity. Medical history, obstetric background, and current labor-related data were compared. Further univariate and multivariable analyses were performed, assessing for risk factors for OASI. RESULTS: One hundred eight parous women who had a diagnosis of OASI and a control group of 216 parturients who delivered without OASI were included in the final analysis. Differences between the current BW and the preceding and maximal previous BW were evaluated. There were significantly higher rates of women who had a larger neonate with > 500 g difference between the current and previous BW in the OASI group than in those with no OASI (28.7% vs. 12.30%, respectively; p < 0.001). Following a multivariable analysis for the dependent parameter of OASI, the following parameters were found to be independently associated with OASI outcome: previous operative vaginal delivery, BW ≥ 90th percentile, and current BW ≥ 500 g compared to previous maximal BW. CONCLUSIONS: In parous women, neonatal BW increase between deliveries of > 500 g is associated with OASI.

Absorbable versus Permanent Suture for Vaginal Uterosacral Ligament Suspension for Treatment of Apical Prolapse.

STUDY OBJECTIVE: The aim of this study was to compare surgical outcomes in women undergoing vaginal uterosacral ligament suspension using permanent as opposed to absorbable sutures. We also aimed to assess for specific risk factors for suture complications. DESIGN: Retrospective cohort study. SETTING: Female pelvic medicine and reconstructive surgery unit at a university-affiliated tertiary medical center. PATIENTS: Women with apical prolapse who underwent vaginal hysterectomy with uterosacral ligament suspension during the study period. INTERVENTIONS: none. MEASUREMENTS AND MAIN RESULTS: A total of 197 women were included in the study. Of them, 118 (59.9%) underwent the procedure using a permanent suture and 79 (40.1%) using an absorbable suture. Women in the permanent suture group were less sexually active and had less prolapse of point C on pre-operative exam. With regard to intra-operative and postoperative data, women in the permanent suture group had increased frequency of concomitant procedures, regional anesthesia, surgical time, duration of hospital stay, and change in hemoglobin. Clinical, anatomical, and composite success did not differ between groups. Patient satisfaction recorded using the Patient Global of Improvement Questionnaire was similar as well. Women in the permanent suture group had a higher frequency of suture exposure compared with the absorbable suture group (9.3% vs 0.0%, p = .006). In order to assess for risk factors leading to suture complications, a comparison was performed between women who had suture exposure or granulation tissue and those who did not. Increasing parity by 1 increased the odds of having suture exposure or granulation tissue by a factor of approximately 1.2 (adjusted odds ratio = 1.24; Confidence interval, 1.05-1.47). Women with stage IV prolapse had 3.4 times the odds of suture complication compared with women with stage III prolapse (adjusted odds ratio = 3.4; Confidence interval, 1.1-10.6). CONCLUSION: Use of an absorbable suture affords comparable success and lower frequency of suture exposure compared with permanent sutures in women undergoing vaginal uterosacral ligament suspension for treatment of apical prolapse.

The Effect of Age on Surgical Outcomes Following Uterine Preserving Surgery for Treatment of Apical Prolapse.

STUDY OBJECTIVE: The aim of this study was to evaluate the effect of age on outcomes after uterine-preserving surgical treatment for apical prolapse. DESIGN: Retrospective cohort study. SETTING: Female pelvic medicine and reconstructive surgery unit at a tertiary, university-affiliated teaching medical center. PATIENTS: Women who underwent surgical management of apical prolapse with uterine preservation between 2010 and 2020. Excluded were women who had ≤1 month of follow-up and those for whom medical records were substantially incomplete. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Included in the study were 140 women who underwent apical prolapse repair with uterine preservation and who met the inclusion criteria. The cohort was divided into 2 groups: (1) women aged 65 years and older (≥65 group) and (2) women younger than 65 years of age (<65 group). Pre-, intra-, and postoperative data were compared between the groups. A total of 103 women (73.6%) were in the <65 group and 37 women (26.4%) in the ≥65 group. Mean age for the entire cohort was 58 ± 9.8 years, body mass index 25.9 ± 4.8 kg/m2, and duration of follow-up was 25.9 ± 21.0 months. Women in the ≥65 group had more comorbidities, were less sexually active, and were less likely to have a midurethral sling performed during their surgery. Clinical and anatomical success rates were somewhat higher in the ≥65 group; however, these differences did not reach statistical significance (97.3% vs 85.4%, p = .069 and 89.2% vs 81.2%, p = .264, respectively). Composite outcome success was higher in the ≥65 group (89.2% vs 72.5%, p = .039). Patient satisfaction recorded using the Patient Global Impression of Improvement questionnaire was high for both groups. A multivariable logistic regression analysis for the dependent parameter of composite outcome success was performed, during which none of the parameters investigated reached statistical significance. Subgroup analysis was performed including only women who were postmenopausal. This was done to address the possible confounding effect that menopausal status may have had on our results. No differences were found between the groups with regard to clinical, anatomical, and composite outcomes. CONCLUSION: Uterine-preserving surgery is a safe and effective surgical treatment for women aged ≥65 years.

Urinary bladder injury during cesarean delivery: risk factors and the role of retrograde bladder filling.

INTRODUCTION AND HYPOTHESIS: Urinary bladder injury during cesarean delivery is an uncommon complication with substantial maternal morbidity. The aim of this study was to identify possible risk factors for bladder injury during cesarean delivery and to describe the role of retrograde bladder filling in the assessment of bladder wall integrity. METHODS: A retrospective cohort study at a large tertiary referral center. Women who underwent cesarean delivery between 2003 and 2017 were included. Women diagnosed with urinary bladder injury were compared to women who did not have such injuries. Data retrieved included demographic characteristics, general medical history, obstetric history and intra-partum and intra-operative data. Information regarding use of retrograde bladder filling intra-operatively was retrieved as well. RESULTS: During the study period, 21,177 cesarean deliveries were performed of which 68 (0.3%) cases of urinary bladder injury were identified. Two-thirds of injuries were located at the urinary bladder dome with the remaining third located at the posterior bladder wall. Most injuries were formed during uterine incision extension (60.0%) followed by peritoneal entry (22.0%). Following uni- and multivariate analyses, three parameters remained independent risk factors for bladder injury: urinary bladder adhesions, failed vacuum attempt prior to cesarean delivery and size of the uterine incision extension. In 15.4% of cases in which retrograde bladder filling was utilized following bladder repair, leakage of fluid was evident. CONCLUSION: Urinary bladder adhesions, failed vacuum attempt prior to cesarean delivery and size of uterine incision extension are independent risk factors for urinary bladder injury during cesarean delivery.

Prediction model for obstetric anal sphincter injury using machine learning.

INTRODUCTION AND HYPOTHESIS: Obstetric anal sphincter injury (OASI) is a complication with substantial maternal morbidity. The aim of this study was to develop a machine learning model that would allow a personalized prediction algorithm for OASI, based on maternal and fetal variables collected at admission to labor. MATERIALS AND METHODS: We performed a retrospective cohort study at a tertiary university hospital. Included were term deliveries (live, singleton, vertex). A comparison was made between women diagnosed with OASI and those without such injury. For formation of a machine learning-based model, a gradient boosting machine learning algorithm was implemented. Evaluation of the performance model was achieved using the area under the receiver-operating characteristic curve (AUC). RESULTS: Our cohort comprised 98,463 deliveries, of which 323 (0.3%) were diagnosed with OASI. Applying a machine learning model to data recorded during admission to labor allowed for individualized risk assessment with an AUC of 0.756 (95% CI 0.732-0.780). According to this model, a lower number of previous births, fewer pregnancies, decreased maternal weight and advanced gestational week elevated the risk for OASI. With regard to parity, women with one previous delivery had approximately 1/3 of the risk for OASI compared to nulliparous women (OR = 0.3 (0.23-0.39), p < 0.001), and women with two previous deliveries had 1/3 of the risk compared to women with one previous delivery (OR = 0.35 (0.21-0.60), p < 0.001). CONCLUSION: Our machine learning-based model stratified births to high or low risk for OASI, making it an applicable tool for personalized decision-making upon admission to labor.

Obstetric anal sphincter injury following previous vaginal delivery.

INTRODUCTION AND HYPOTHESIS: Obstetric anal sphincter injury (OASI) is a debilitating complication of vaginal delivery. The aim of this study was to identify risk factors for OASI in women with a previous vaginal delivery. We further attempted to detect specific risk factors for severe OASI in this subgroup. METHODS: We conducted a retrospective cohort study between 2003 and 2019. The study group included women who had a singleton, live, vertex, vaginal delivery at term and who also had at least one previous vaginal delivery. The control group included women with at least one previous vaginal delivery without OASI. General medical history, obstetric history, and ante-, intra- and post-partum data were collected and compared between groups. RESULTS: Following implementation of the inclusion criteria, 79,176 women were included. Allocation to study groups was according to OASI occurrence: 135 patients (0.2%) had a third- or fourth-degree perineal tear, while 79,041 patients (99.8%) had no such injury. Multivariate analysis revealed that one previous vaginal delivery, birthweight ≥ 3900 g (90th percentile), vacuum-assisted vaginal delivery and episiotomy were associated with increased risk of OASI. Comparison of more severe OASI (3C and 4th-degree) cases to the control group showed similar results with the addition of prolonged second stage and younger age to risk factors associated with severe OASI while episiotomy was no longer significant. CONCLUSION: In women with a previous vaginal delivery, one vs. two or more previous vaginal deliveries, increased birthweight, vacuum-assisted vaginal delivery and episiotomy are risk factors for OASI.

Laparoscopic uterosacral ligament suspension versus vaginal colposuspension using the Uphold Lite™ mesh system: clinical outcome and patient satisfaction.

INTRODUCTION AND HYPOTHESIS: The objective was to compare clinical and anatomical outcomes between laparoscopic uterosacral ligament suspension (LUSLS) and vaginal colposuspension using the Uphold Lite™ mesh system for the treatment of apical prolapse. METHODS: We performed a comparative, retrospective cohort study. All women who underwent either vaginal colposuspension with the Uphold Lite™ System or LUSLS for treatment of apical prolapse between 2010 and 2019 were included. The groups were compared with regard to demographic, pre-operative, intra-operative, and post-operative data. Outcome measures included clinical and anatomical cure, as well as a composite outcome. The PGI-I questionnaire was used to determine patient satisfaction. RESULTS: One-hundred and nineteen women met the inclusion criteria, including 70 women who underwent LUSLS and 49 women who underwent vaginal colposuspension with the Uphold Lite™ mesh system. At a mean follow-up of 31.7 (SD = 18.1) months, the clinical cure rate was high for both groups, reaching 98.6% in the LUSLS group compared with 89.8% in the Uphold group (NS). Anatomical cure rate was 83.6% in the LUSLS group compared with 69.7% for the Uphold group (NS). With regard to the composite outcome, no difference was found, although a trend towards a higher success rate was noted in the LUSLS group (83.6% vs 66.7%, p = 0.055). Patient satisfaction measured using the PGI-I questionnaire was high, at 98.6% in the LUSLS group and 87.8% in the Uphold group (NS). CONCLUSION: Laparoscopic uterosacral ligament suspension and vaginal colposuspension using the Uphold Lite™ mesh system both have high clinical cure rates.

Obstetric anal sphincter injury in adolescent mothers.

BACKGROUND: Obstetric anal sphincter injury (OASI) is a debilitating complication of vaginal delivery which has yet to receive ample attention in adolescents. The aim of this study was to describe risk for OASI in adolescent mothers compared to adults. We further attempted to compare risk factors for OASI between these two age groups. METHODS: We performed a retrospective cohort study between 2003 and 2019. Primiparous women who delivered vaginally, 21 years and younger were compared to women ages 26-35. Excluded were preterm, multifetal, non-vertex, cesarean deliveries as well as intrauterine fetal death. Rate of OASI as well as obstetric and labor characteristics of women with OASI, were compared between groups. Finally, risk factors were assessed for each group separately. Univariate and multivariate logistic regression model were performed. RESULTS: Final analysis was performed on 5113 nulliparous adolescents and 13,845 nulliparous in the 26-35 age group. Allocation to study groups was according to OASI - Sixty-seven adolescents (1.3%) had a 3rd or 4th degree perineal tear and were defined as the OASI group, while 5046 patients (98.7%) did not have such a tear. In the adult group, 199 out of 13,845 patients (1.4%) were diagnosed with OASI. Occurrence of OASI did not differ between groups (p = 0.510). Comparison of women with OASI in the adolescent group vs. adult group found differences with regard to operative vaginal delivery, (20.9% vs. 36.2%, respectively; p = 0.023) and meconium stained amniotic fluid (9.1% vs. 21.3%, respectively; p = 0.027). Following multivariate analysis the only parameter independently associated with OASI in the adolescent age group was head circumference ≥ 90th percentile with an adjusted odds ratio of 3.08 (CI 1.48-6.38, p = 0.003). In the adult group the similar analysis revealed operative vaginal delivery (OR = 2.44, CI 1.72-3.47, p < 0.001) and a birthweight≥90th percentile (OR = 2.23, CI 1.19-4.18, p = 0.012) to be independent risk factors for OASI. CONCLUSION: Adolescents have similar risk for OASI compared to adults but differ in risk factors leading to OASI. Head circumference ≥ 90th percentile was found to be associated with OASI in this age group.

Urinary dysfunction in women following total mesorectal excision versus partial mesorectal excision for treatment of rectal cancer.

BACKGROUND: Colorectal cancer is a condition which is associated with substantial morbidity and mortality. The aim of this study was to assess urinary dysfunction and its effect on quality of life in women who underwent total mesorectal excision compared to women treated by partial mesorectal excision for treatment of rectal cancer. METHODS: We performed a retrospective cohort study at a tertiary university hospital between January 2014 and December 2019. A comparison was performed between women who underwent total mesorectal excision as opposed to partial mesorectal excision for treatment of rectal cancer. Pre-operative, intra-operative and post-operative data were compared between groups. Data regarding radiation therapy was recorded and compared as well. Urinary dysfunction and its impact on quality of life were assessed using UDI-6 and USIQ questionnaires. Further univariate and multivariate analyses were performed in the attempt of assessing risk factors for urinary dysfunction. RESULTS: A total of 107 women were included in the study, 73 women underwent partial mesorectal excision as opposed to 34 women who were treated by total mesorectal excision. Twenty-five women in the TME group underwent radiation therapy prior to surgery as opposed to none in the PME group (p < 0.001). Urinary dysfunction following surgery as assessed using the UDI-6 questionnaire did not differ between groups. Similar findings were recorded with regard to the impact of urinary dysfunction on quality of life as assessed using the USIQ questionnaire. Following multivariate analysis longer hospital stay was associated with increased risk of some degree of urinary dysfunction. CONCLUSIONS: Women undergoing total mesorectal excision have comparable results to partial mesorectal excision with regard to urinary dysfunction.

Vaginal Colposuspension Using the Uphold Lite Mesh System versus Transvaginal Hysterectomy with Uterosacral Ligament Suspension for Treatment of Apical Prolapse: A Comparative Study.

STUDY OBJECTIVE: To compare clinical and anatomic outcomes as well as patient satisfaction in women undergoing vaginal colposuspension using the Uphold Lite system (Boston Scientific Corporation, Marlborough, MA) and transvaginal hysterectomy with uterosacral ligament suspension (VUSLS) for the treatment of apical prolapse. DESIGN: Retrospective cohort study. SETTING: Female pelvic medicine and reconstructive surgery unit at a university-affiliated tertiary medical center. PATIENTS: Women with apical prolapse who underwent either vaginal colposuspension using the Uphold Lite system (uterine-preserving as well as after previous hysterectomy) or VUSLS from 2010 to 2019. Excluded were women with 1 month or less of follow-up. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 164 women were included in the study: 112 women underwent VUSLS, and 52 underwent colposuspension using the Uphold Lite mesh system. Age, body mass index, maximal birth weight, comorbidity rates, and pelvic organ prolapse severity were similar between the groups. The clinical cure rate was similarly high in both groups, with 91.1% in the women who underwent VUSLS and 88.5% in those in the Uphold Lite group (p = .60). No differences were noted between the groups with regard to anatomic cure rate or composite outcome success rate (73.9% vs 76.0%, p = .77 and 70.3% vs 74.0%, p = .63, in the VUSLS and Uphold Lite groups, respectively). An advantage was noted in the VUSLS group with regard to patient satisfaction with 98.1% of the women stating that their condition was very much better (Patient Global Impression of Improvement questionnaire: A) or much better (Patient Global Impression of Improvement questionnaire: B) compared with 83.9% of the women in the Uphold Lite group (p = .023). In an attempt to assess the association between different variables and the composite outcome, a multivariate analysis was performed in which increased body mass index, menopausal status, and increased preoperative genital hiatus were found to decrease composite outcome success. CONCLUSION: Vaginal colposuspension using the Uphold Lite system and VUSLS for the treatment of apical prolapse have comparable results with high clinical success rates.

Age-associated differences in macrophage response in a vaginal wound healing rat model.

INTRODUCTION AND HYPOTHESIS: Surgical treatment of pelvic organ prolapse often includes the use of patients' vaginal connective tissue. Wound healing appears to play an important part in the success of such procedures. The aim of this study was to describe the effect of age on inflammatory processes, specifically macrophage response, involved in vaginal wound healing. METHODS: Twenty-five young (12 weeks old) and 25 old (12 months old) virgin female Fischer rats underwent a standardized 9-mm posterior midline vaginal incision. Tissue samples were taken for histological analysis on days 1, 3, 7, 14 and 30 post-injury. Parameters evaluated included wound area, macrophage number and expression of inflammatory markers including tumor necrosis factor alpha (TNFa), inducible nitric oxide synthase (iNOS), CCR7/CD197, arginase I and CD163/M130. RESULTS: Microscopic examination of the vaginal wounds over time demonstrated a clear difference between young and old rats in spontaneous healing capacity. The average wound area in young rats 1 day after injury was significantly smaller than in old rats (16.5 ± 1.7 vs. 23.8 ± 1.5 mm2, P < 0.05). At 3 days post-injury, wounds were closed in young rats but still open in old rats (wound area: 13.5 ± 1.5 mm2). Old rats demonstrated a more excessive and sustained macrophage response compared with young rats. They also demonstrated a disordered pattern of macrophage expression over time, with a prolonged expression of TNFa and iNOS in the tissue and a disordered M2 macrophage response. CONCLUSION: Excessive and prolonged macrophage response in older rats may contribute to poor wound healing in the vagina.

Age-associated impairments in tissue strength and immune response in a rat vaginal injury model.

INTRODUCTION AND HYPOTHESIS: Surgical repair of pelvic organ prolapse often includes native tissue repair during which the patient's own vaginal connective tissue is used to achieve pelvic support. This method, based on plication and suspension often yields suboptimal anatomical outcomes, possibly due to inadequate healing of the vaginal connective tissue. We hypothesized that age might have a negative effect on the time course and tissue biomechanics of vaginal wound healing in a rat model. METHODS: Fifty young (12 weeks) and old (12 months) female 344BN Fischer rats were subjected to a posterior midline vaginal incision. The time course of repair was determined by measuring the size of the wound on days 1, 3, 7, and 14 post-injury. These findings correlated with the immune response to injury using a marker of impaired wound healing, the inflammatory cytokine macrophage migration inhibitory factor in the vaginal muscularis. Biomechanical properties of the healed vaginal tissue were tested 30 days post-injury. RESULTS: Wound healing was assessed on days 1, 3, 7, and 14 post-injury. On day 3 post-injury, the wounds in the young animals had all closed whereas the wounds in the old animals remained open. Furthermore, on day 7, the wound gap was still filled with granulation tissue in the old rats, whereas for the young rats, the wound area was almost indistinguishable from the non-injured area. Macrophage migration inhibitory factor was highly expressed in the vaginal epithelium and in the vaginal muscularis after injury. When compared with young animals, macrophage migration inhibitory factor levels of old rats began to rise more than 2 days later and the increased tissue expression persisted for 7 days longer. The breakpoint force of the healed vagina of old rats was almost 4-fold weaker than in young rats. At 30 days post-injury, the healed vagina in old rats regained less of the original (healthy) force at breakpoint than the young rats. CONCLUSIONS: In this rat model, age impaired vaginal wound healing, which was reflected in the altered inflammatory response to injury and reduced tissue strength.

Symptomatic pelvic hematoma following hysterectomy: risk factors, bacterial pathogens and clinical outcome.

BACKGROUND: Pelvic hematoma is a common finding following hysterectomy which at times may become infected causing substantial morbidity. The aim of this study was to describe the incidence, clinical manifestation and identify risk factors for infected pelvic hematoma. We also attempted to identify specific bacterial pathogens which may cause this phenomenon. METHODS: We conducted a retrospective cohort study at a tertiary university teaching hospital. Included were all women who underwent hysterectomy and were diagnosed with a pelvic hematoma following surgery from 2013 to 2018. In an attempt to assess possible risk factors for infected pelvic hematoma women with asymptomatic pelvic hematoma were compared to women with an infected pelvic hematoma. RESULTS: During the study period 648 women underwent hysterectomy at our medical center. Pelvic hematoma was diagnosed by imaging in 50 women (7.7%) including 41 women who underwent vaginal hysterectomy and 9 women who underwent abdominal hysterectomy. In 14 (2.2%) cases the hematoma became infected resulting in need for readmission and further treatment. Women who underwent vaginal surgery were more likely to return with infected pelvic hematoma compared to women who underwent open abdominal or laparoscopic surgery (4.5% vs. 1.1%, p < 0.05). In 8 women bacterial growth from hematoma culture was noted. Enterococcus faecalis, was the most abundant pathogen to be isolated in this sub-group. CONCLUSION: Vaginal route of hysterectomy is a risk factor for infected pelvic hematoma following hysterectomy. Most of these infections were caused by anaerobic bacteria which may not be sufficiently covered by current antibiotic prophylactic regimens.

Novel Incision-free Device for Transvaginal Apical Pelvic Organ Prolapse Repair.

STUDY OBJECTIVE: The purpose of this study was to present the feasibility and potential clinical advantages of Apyx (Escala Medical, Israel), a minimally invasive incision-free anchoring device, for apical prolapse repair. DESIGN: An experimental prospective animal and cadaver study. SETTING: Animal facility and a cadaver laboratory of a tertiary care teaching hospital. PATIENTS: Included in this study were 7 ovine models, 2 porcine specimens, and 3 fresh unembalmed female human cadavers. INTERVENTIONS: The Apyx device for sacrospinous ligament (SSL) suspension was tested on ovine and porcine models. The pullout force needed to detach the Apyx anchor from the SSL was measured. Safety, reliability, and feasibility of this new incision-free procedure were also tested on an ovine model and human cadavers. The precision in deployment of the Apyx device to the SSL was tested via palpation by the surgeon, tissue dissection, and x-ray imaging. The efficacy was tested both by pullout forces and histologic analysis of the vaginal attachment to the SSL. MEASUREMENTS AND MAIN RESULTS: Forty-two anchors were inserted into the SSLs on ovine and porcine models and on cadaver SSLs. No abnormalities or malfunctions were noted in the functional performance of the anchors or the retrieval device. Mean pullout force for the ovine animal model was 38.64 ± 2.80 N. Pullout force in the porcine model was found to be in correlation with the values observed in the ovine model. None of the measured forces was below 20 N. Accuracy and safety tests showed good consistency when deploying the Apyx device to the SSL with no damage to surrounding organs in the ovine or the human cadaver model. Histology demonstrated biologic adhesion characterized by a gross assessment of a newly formed, firm fibrotic tissue 12 weeks after anchor deployment. CONCLUSION: The Apyx anchoring system, a novel incision-free minimally invasive prolapse repair device, demonstrated an anatomically feasible, easy-to-use procedure for suspending the vaginal apex to the SSLs. Its clinical safety, efficacy, and impact on patient symptoms and quality of life should be further studied.

Laparoscopic Uterosacral Ligament Hysteropexy vs Total Vaginal Hysterectomy with Uterosacral Ligament Suspension for Anterior and Apical Prolapse: Surgical Outcome and Patient Satisfaction.

STUDY OBJECTIVE: To compare anatomic and clinical cure rates as well as patient satisfaction between uterine-preserving laparoscopic uterosacral ligament suspension and total vaginal hysterectomy with uterosacral ligament suspension in women with apical and anterior prolapse. DESIGN: Single-center clinical comparative retrospective cohort study. SETTING: A female pelvic medicine and reconstructive surgery service at a tertiary teaching hospital. PATIENTS: Women with pelvic organ prolapse who underwent surgical treatment for their condition between July 2010 and December 2015. INTERVENTIONS: All women underwent laparoscopic uterosacral ligament suspension or total vaginal hysterectomy with uterosacral ligament suspension for apical and anterior prolapse. Concomitant procedures included anterior and posterior repair, as well as a midurethral sling when indicated. MEASUREMENTS AND MAIN RESULTS: Preoperative and postoperative Pelvic Organ Prolapse Quantification (POP-Q) measurements were obtained. The primary outcome was clinical cure rate. Secondary outcomes included anatomic cure rate and outcomes of site-specific POP-Q points Ba, C, and Bp for the whole cohort. Patient satisfaction was measured using the Patient Global Impression of Improvement questionnaire. During the study period, 106 women underwent transvaginal hysterectomy with uterosacral ligament suspension, and 53 women had laparoscopic uterosacral ligament suspension. At a mean follow-up of 14.7 ± 13.23 months for the vaginal group and 17.5 ± 15.84 months for the laparoscopic group (p = .29), there were significant improvements of POP-Q points Ba, C, and Bp (p < .0001 for all comparisons in both groups). The clinical cure rate was 96% in the vaginal group and 98% in the laparoscopic group (p = .50). The anatomic cure rate was 85.4% in the vaginal group and 93.75% in the laparoscopic group (p = .11) Patient satisfaction was high in both groups. CONCLUSION: In appropriately selected patients, laparoscopic uterosacral ligament suspension is a valid uterus-preserving option for women with anterior and apical prolapse, associated with high anatomic and clinical cure rates and patient satisfaction.

Use of multimedia during informed consent: novelty or necessity.

The process of informed consent is an integral part of the preoperative encounter. In theory, it has the potential to educate patients, enabling them to reach a true autonomous decision regarding the treatment offered. Unfortunately, in recent years informed consent has become overly complicated for the average patient. Questions have been raised regarding the ability of the process, as practiced nowadays, to actually increase knowledge and achieve its goals. In search of new ways to increase patient comprehension, researchers have suggested use of multimedia during the process of informed consent. Visualization of complex ideas, interactive learning and tailoring the procedure to fit patient needs are all advantages presented by use of multimedia during the process. Several randomized prospective trials have looked into this topic and have presented promising data in favor of multimedia use. Informed consent is a process with unfulfilled potential, and use of multimedia may be part of the solution. In our opinion, it is time to change the way we educate patients.