Neuron deficit in the white matter and subplate in periventricular leukomalacia.

OBJECTIVE: The cellular basis of cognitive abnormalities in preterm infants with periventricular leukomalacia (PVL) is uncertain. One important possibility is that damage to white matter and subplate neurons that are critical to the formation of the cerebral cortex occurs in conjunction with oligodendrocyte and axonal injury in PVL. We tested the hypothesis that the overall density of neurons in the white matter and subplate region is significantly lower in PVL cases compared to non-PVL controls. METHODS: We used a computer-based method for the determination of the density of microtubule-associated protein 2-immunolabeled neurons in the ventricular/subventricular region, periventricular white matter, central white matter, and subplate region in PVL cases and controls. RESULTS: There were 5 subtypes of subcortical neurons: granular, unipolar, bipolar, inverted pyramidal, and multipolar. The neuronal density of the granular neurons in each of the 4 regions was 54 to 80% lower (p≤0.01) in the PVL cases (n=15) compared to controls adjusted for age and postmortem interval (n=10). The overall densities of unipolar, bipolar, multipolar, and inverted pyramidal neurons did not differ significantly between the PVL cases and controls. No granular neurons expressed markers of neuronal and glial immaturity (Tuj1, doublecortin, or NG2). INTERPRETATION: These data suggest that quantitative deficits in susceptible granular neurons occur in the white matter distant from periventricular foci, including the subplate region, in PVL, and may contribute to abnormal cortical formation and cognitive dysfunction in preterm survivors.

Surgical Complications and Hospital Costs in Robot-Assisted Versus Conventional Laparoscopic Hysterectomy With Concurrent Sacrocolpopexy: Analysis of the Nationwide Readmissions Database.

OBJECTIVES: Despite increasing use of robotic technology for minimally invasive hysterectomy with sacrocolpopexy, evidence supporting the benefits of these costly procedures remains inconclusive. This study aimed to compare differences in perioperative complications, 30-day readmissions, and costs between robot-assisted and conventional laparoscopic hysterectomy with concurrent sacrocolpopexy using a large national database. METHODS: Using the 2009-2015 Nationwide Readmissions Database and procedure codes, we identified patients who underwent a robot-assisted or conventional laparoscopic hysterectomy with sacrocolpopexy. We measured in-hospital perioperative complications using diagnosis and procedure codes and measured 30-day readmissions based on patient linkages across hospitalizations. Hospital costs were estimated using charges and cost-to-charge ratios. These outcomes were compared between robot-assisted and conventional laparoscopic procedures using bivariate and multivariable regression analysis. RESULTS: Our weighted sample included a total of 7,675 patients. Major perioperative complications occurred in 6.7% of robot-assisted and 11.2% of conventional laparoscopic procedures (unadjusted P < 0.001; adjusted odds ratio, 0.69; 95% confidence interval, 0.51-0.93; P = 0.02). Hospital costs were higher in robot-assisted than in conventional laparoscopic procedures (respective median costs, $16,367 vs $13,898; P < 0.001), with an adjusted cost ratio of 1.24 (95% confidence interval, 1.17-1.31; P < 0.001). The risk of 30-day readmission was similar between robot-assisted and conventional laparoscopic procedures. CONCLUSIONS: Nationally representative data suggest that, in laparoscopic hysterectomy with sacrocolpopexy, the robot-assisted approach is associated with a lower risk of perioperative complications, despite higher costs, compared with the conventional one. The risk of 30-day readmission was similar between the robot-assisted and conventional laparoscopic approaches.

Success of Concomitant Versus Interval Slings for Prevention and Treatment of Bothersome de Novo Stress Urinary Incontinence.

BACKGROUND: Despite large trials designed to guide management on whether to perform a prophylactic continence procedure at the time of pelvic organ prolapse (POP) repair, it remains unclear if a staged or interval approach confers advantages in treatment of bothersome stress urinary incontinence (SUI) in women without bothersome SUI before their POP repair. OBJECTIVE: The objective of this study was to compare success of concomitant versus interval slings for the prevention/treatment of de novo bothersome SUI after POP repair. STUDY DESIGN: This multicenter retrospective cohort with prospective follow-up enrolled women with minimal or no SUI symptoms who underwent minimally invasive apical surgery for stage 2 or higher POP between 2011 and 2018 and had a concomitant sling placed at the time of POP surgery or an interval sling placed. Prospectively, all patients were administered the Urogenital Distress Inventory Short-Form 6, the Patient Global Impression of Improvement, and questions on reoperation/retreatment and complications. RESULTS: A total of 120 patients had concomitant slings, and 60 had interval slings. There were no differences in the proportion of patients who had intrinsic sphincter deficiency (22% vs 20%), although the concomitant sling group was more likely to have a positive cough stress test result (30% vs 8%, P = 0.006). The interval sling group was more likely to report "yes" to SUI symptoms on Urogenital Distress Inventory Short-Form 6 (3% vs 30%, P = 0.0006) and during their postoperative visit (0% vs 24%, P < 0.0001). There were no differences in surgical complications. CONCLUSIONS: Among women with minimal or no SUI symptoms undergoing prolapse repair, concomitant slings resulted in lower rates of bothersome SUI compared with similar women undergoing interval sling placement.

Unanticipated Uterine and Cervical Malignancy in Women Undergoing Hysterectomy for Uterovaginal Prolapse.

OBJECTIVE: This study aimed to determine the prevalence of unanticipated uterine cancer and cervical cancer in women undergoing hysterectomy for uterovaginal prolapse. METHODS: Using data from the 2015-2018 American College of Surgeons National Surgical Quality Improvement Program, we identified adult women who underwent a hysterectomy with a concurrent procedure for uterovaginal prolapse. Patients who underwent a radical hysterectomy or had other procedures or diagnoses suggestive of preoperatively suspected or known gynecologic cancer were excluded. Our outcome measures were pathology-confirmed diagnoses of uterine cancer and cervical cancer. Bivariate statistical tests and multivariable logistic regression were used to identify patient characteristics associated with the likelihood of having unanticipated uterine cancer. RESULTS: Among 9,687 patients meeting the sample eligibility criteria (median age, 60 years), 51 (0.53%; 95% confidence interval, 0.39%-0.69%) had a diagnosis of uterine cancer. Forty-three (84.3%) were stage I-IB. Multivariable logistic regression showed that older age (adjusted odds ratio, 2.75; 95% confidence interval, 1.47-5.51, for age >60 vs 41-60 years) and uterine weight greater than 250 g (adjusted odds ratio, 4.34; 95% confidence interval, 1.48-10.79) were associated with a significantly higher likelihood of having unexpected uterine malignancy. In addition, in a subsample of 7,908 patients who underwent a total hysterectomy, 7 (0.09%; 95% confidence interval, 0.04%-0.18%) had a diagnosis of cervical cancer. CONCLUSIONS: The risk of unexpected uterine cancer and cervical cancer in women undergoing hysterectomy for uterovaginal prolapse was relatively low but should be appropriately considered when counseling patients desiring uterine- or cervix-sparing procedures.

Virtual Interviews During COVID-19: Perspectives of Female Pelvic Medicine and Reconstructive Surgery Program Directors.

OBJECTIVE: The aim of the study was to evaluate female pelvic medicine and reconstructive surgery (FPMRS) fellowship program directors' opinions regarding the effectiveness of virtual interviews for selecting fellows and their future interview mode preferences. METHODS: This was a cross-sectional online survey of all FPMRS program directors in the United States conducted from April 29, 2020, to May 30, 2020. At the time of this study, there were 73 program directors and 69 obstetrics and gynecology and urology-accredited FPMRS programs nationwide. The primary outcome was to subjectively assess the effectiveness of virtual interviews as compared with in-person interviews for evaluating applicants. RESULTS: Fifty seven (82.6%) of the program directors completed the survey. A total of 80.7% (46/57) of the respondents had participated in interviews for the active match cycle. Of the programs that participated in the interview process, almost all conducted interviews using virtual platforms (97.8%, 45/46). Program directors who conducted interviews virtually found them effective in evaluating applicants (88.9%, 40/45) and were satisfied with the virtual interview process (86.7%, 39/45). A total of 31.1% of respondents (14/45) preferred a virtual platform to an in-person setting for future interviews, and 60% (27/45) reported that they will likely perform future interviews virtually. CONCLUSIONS: Although the pandemic resulted in a sudden reformatting of FPMRS fellowship interviews, most program directors nationally were satisfied with the process and found virtual interviews effective for assessing applicants. More than 50% of FPMRS program directors are likely to consider the virtual format for future interviews.

Trends in Surgical Exposure and Experience in Female Pelvic Medicine and Reconstructive Surgery Fellowship Programs.

OBJECTIVES: This study aimed to characterize variations in female pelvic medicine and reconstructive surgery (FPMRS) fellows' surgical experiences, concurrence with Accreditation Council for Graduate Medical Education (ACGME) proposed procedural volume guidelines, and to explore how these factors affect self-assessed preparedness to practice independently upon graduation. METHODS: An electronic survey was sent to 166 fellows enrolled in ACGME-approved FPMRS fellowship programs during the 2017-2018 academic year. The survey included questions on demographics, program specifics, desires for future practice, case volume, and self-assessed ability to independently perform selected procedures. RESULTS: A total of 99 fellows responded, yielding a 59.6% (99/166) response rate. Procedures assessed as "core" urogynecologic surgeries were midurethral sling, sacral nerve stimulator placement, abdominal sacrocolpopexy, laparoscopic sacrocolpopexy, extraperitoneal colpopexy, intraperitoneal colpopexy, anterior colporrhaphy, posterior colporrhaphy, colpocleisis, rectovaginal fistula repair, vesicovaginal fistula repair, and urethral diverticulectomy. The percentage of third-year respondents meeting proposed ACGME guidelines varied from 56.3% (18/32; sling procedures) to 96.9% (31/32; intraperitoneal colpopexy and rectovaginal fistula repair). Although 67.7% (67/99) of all respondents reported that they did not expect to feel qualified to perform at least one of these procedures independently upon graduation from fellowship, 99.0% (98/99) predicted that they would be adequately trained overall to practice independently upon graduation. CONCLUSIONS: Surgical experience varied among FMPRS surgical fellows. Case volume was somewhat but not completely associated with self-perceived ability to practice a procedure independently.

Neuronal cell death in the arcuate nucleus of the medulla oblongata in stillbirth.

The hypothesis that unexplained stillbirth arises in a similar manner as the sudden infant death syndrome (SIDS) is based in part on shared neuropathologic features between the two entities, including hypoxic-ischemic lesions such as white matter and brainstem gliosis, as well as aplasia or hypoplasia of the arcuate nucleus on the ventral surface of the medulla. The arcuate nucleus is the putative homologue of the respiratory chemosensory region at the ventral medullary surface in animals that is involved in central chemosensitivity. To determine arcuate nucleus pathology in stillbirth, and its co-occurrence with evidence of hypoxia-ischemia, we reviewed brain specimens from the archives of our hospitals from 22 consecutive stillbirths from 22 to 41 gestational weeks. Explained causes of death (n=17) included nuchal cord, acute chorioamnionitis, placental abruption, and fetal glomerulosclerosis; 5 cases were unexplained. In 12 brains, we observed nuclear karyorrhexis and/or pyknosis with cytoplasmic hypereosinophilia in neurons in the arcuate nucleus in both explained (n=8) and unexplained (n=4) cases (54.5% of total cases). Three additional cases had arcuate aplasia (n=1) or hypoplasia (n=2) (13.6% of total cases); one of the latter cases also had neuronal necrosis in the hypoplastic arcuate. The degree of gliosis in the region of the arcuate nucleus was variable across all cases, without statistically significant differences between groups with and without arcuate nucleus necrosis. Other lesions in association with (n=14) and without (n=8) arcuate nucleus abnormalities were diffuse cerebral white matter gliosis, periventricular leukomalacia (PVL), and neuronal necrosis in the hippocampus, basal ganglia, thalamus, basis pontis, and brainstem tegmentum. In 16/20 (80.0%) cases (with or without histologic necrosis of the arcuate), immunostaining with caspase-3 demonstrated positive neurons. Our findings suggest that neuronal pathology in the arcuate nucleus may be both developmental (13.6%) and acquired (54.5%). The association of neuronal necrosis and apoptosis in the arcuate nucleus with systemic entities involving fetal ischemia, and with other brain lesions consistent with ischemia, e.g., cerebral white matter gliosis, suggests that ischemia plays a role in the arcuate nucleus damage as well. Thus, the underpopulation of arcuate neurons detected postnatally in some SIDS infants may be secondary to an acquired insult in mid- or late gestation, and in other cases, a primary developmental lesion in early gestation, or both. The role of arcuate nucleus pathology in the pathogenesis of fetal demise remains to be determined.

Decreased Surgical Site Infection Rate in Hysterectomy: Effect of a Gynecology-Specific Bundle.

OBJECTIVE: We implemented a hysterectomy-specific surgical site infection prevention bundle after a higher-than-expected surgical site infection rate was identified at our institution. We evaluate how this bundle affected the surgical site infection rate, length of hospital stay, and 30-day postoperative readmission rate. METHODS: This is a quality improvement study featuring retrospective analysis of a prospectively implemented, multidisciplinary team-designed surgical site infection prevention bundle that consisted of chlorhexidine-impregnated preoperative wipes, standardized aseptic surgical preparation, standardized antibiotic dosing, perioperative normothermia, surgical dressing maintenance, and direct feedback to clinicians when the protocol was breached. RESULTS: There were 2,099 hysterectomies completed during the 33-month study period. There were 61 surgical site infections (4.51%) in the pre-full bundle implementation period and 14 (1.87%) in the post-full bundle implementation period; we found a sustained reduction in the proportion of patients experiencing surgical site infection during the last 8 months of the study period. After adjusting for clinical characteristics, patients who underwent surgery after full implementation were less likely to develop a surgical site infection (adjusted odds ratio [OR] 0.46, P=.01) than those undergoing surgery before full implementation. Multivariable regression analysis showed no statistically significant difference in postoperative days of hospital stay (adjusted mean ratio 0.95, P=.09) or rate of readmission for surgical site infection-specific indication (adjusted OR 2.65, P=.08) between the before and after full-bundle implementation periods. CONCLUSION: The multidisciplinary implementation of a gynecologic perioperative surgical site infection prevention bundle was associated with a significant reduction in surgical site infection rate in patients undergoing hysterectomy.

The cerebral cortex overlying periventricular leukomalacia: analysis of pyramidal neurons.

The role of the cerebral cortex in the cognitive deficits in preterm survivors is poorly understood. Periventricular leukomalacia (PVL), the key feature of encephalopathy of prematurity, is characterized by periventricular necrotic foci and diffuse gliosis in the surrounding cerebral white matter. Here, we tested the hypothesis that reductions in the density of layer I neurons and/or pyramidal neurons in layers III and/or V are associated with PVL, indicating cortical pathology potentially associated with cognitive deficits in long-term survivors. In controls (23 gestational weeks to 18 postnatal months) (n = 15), a lack of significant differences in pyramidal density among incipient Brodmann areas suggested that cytoarchitectonic differences across functional areas are not fully mature in the fetal and infant periods. There was a marked reduction (38%) in the density of layer V neurons in all areas sampled in the PVL cases (n = 17) compared to controls (n = 12) adjusted for postconceptional age at or greater than 30 weeks, when the six-layer cortex is visually distinct (P < 0.024). This may reflect a dying-back loss of somata complicating transection of layer V axons projecting through the necrosis in the underlying white matter. This study underscores the potential role of secondary cortical injury in the encephalopathy of prematurity.