A Narrative Review of Current Understanding of the Pathophysiology of Polycystic Ovary Syndrome: Focus on Plausible Relevance of Vitamin D.

Polycystic ovarian syndrome (PCOS) is the most prevalent endocrinopathy of reproductive years. Salient features in presentation of patients PCOS include menstrual dysfunction, hyperandrogenism and/or polycystic appearance of ovaries on ultrasound. While the diagnosis of PCOS depends on presence of specified criteria, misdiagnoses are common. Despite years of extensive research, the exact aetiology of PCOS remains largely unknown. In the past decade, apart from insulin resistance and hyperandrogenemia, anti-mullerian hormone (AMH), an important marker of ovarian reserve, and vascular endothelial growth factor (VEGF), a crucial factor in angiogenesis, have been examined as plausible players of causative relevance for PCOS. Vitamin D, a sex-steroid hormone that is universally known for its relevance for skeletal health, has received increasing attention due to growing evidence supporting its pivotal in reproductive physiology and in PCOS. In this review we summarize our current understanding of the mechanisms relevant to the pathophysiology of PCOS and examine the role of vitamin D signalling in this context.

Risk of venous thromboembolism for ovarian cancer patients during first-line therapy after implementation of an Enhanced Recovery After Surgery (ERAS) protocol.

OBJECTIVE: To determine incidence and risk factors for VTE for patients with advanced epithelial ovarian cancer undergoing first-line therapy, including cytoreductive surgery, on an Enhanced Recovery After Surgery (ERAS) protocol. METHODS: Medical records were reviewed for patients with FIGO stage IIIA-IVB epithelial ovarian, fallopian tube, or primary peritoneal cancer undergoing primary or interval cytoreductive surgery from March 2017 through September 2019. All patients were enrolled on an ERAS protocol, including 28-day postoperative VTE prophylaxis. Demographic information, medical history, perioperative characteristics, and ERAS compliance were evaluated using univariate and multivariate models. RESULTS: Of 230 patients undergoing cytoreductive surgery via laparotomy, 155 received neoadjuvant chemotherapy and 75 received primary cytoreduction. 38 patients had a VTE during the study period. 13 events (5.7%) were identified at time of diagnosis, 6 (3.9%) during neoadjuvant chemotherapy, 5 (2.2%) within 30 days after surgery, 5 (2.2%) between 30 days and 6 months after surgery, and 9 (3.9%) after the 6-month window. The cumulative incidence of VTE was 6.1% (95% CI, 4.3-8.8%) within 6 months after diagnosis and 8.5% (6.2-11.4%) within 1 year after diagnosis. Estimated blood loss (adjusted HR 1.22 [95% CI, 1.09-1.36], p = 0.001) and history of VTE (7.06 [2.34-21.29], p = 0.001) were independently associated with VTE. CONCLUSION: With implementation of an ERAS protocol, only 1 in 46 patients experienced a VTE within 30 days after surgery. However, overall VTE occurred in 1 in 16 patients during first-line therapy. Strategies to further reduce VTE risk, especially during neoadjuvant chemotherapy and surveillance, should be investigated.

Randomized controlled trial of single-use negative-pressure wound therapy dressings in morbidly obese patients undergoing cesarean delivery.

BACKGROUND: The single-use negative-pressure wound therapy dressings are designed to use over a closed surgical wound. Early prospective studies suggested that these dressings may be of potential benefit in reducing cesarean wound complications. OBJECTIVE: This study aimed to test the hypothesis that incisional negative-pressure wound therapy decreases postoperative wound morbidity compared with standard surgical dressing in patients with class III obesity undergoing cesarean delivery. STUDY DESIGN: In a single-site, parallel, randomized controlled trial, participants with class III obesity (body mass index ≥40 kg/m2) were recruited to participate in the study. Patients were consented in the ambulatory obstetrical units, on admission to the antepartum service, and on labor and delivery before active labor. Patients who had a cesarean delivery were randomized to either the standard surgical dressing or a prophylactic negative-pressure wound therapy device. The randomization was achieved using permuted blocks of 4, 6, and 8 in a 1:1 allocation ratio. The primary outcome was a composite outcome of wound complications. The planned enrollment of 242 subjects was based on the power to detect a 50% decrease in the composite wound outcome, assuming a 30% baseline wound morbidity rate for this population. The outcomes were assessed by study staff blinded to the patient's treatment arm. RESULTS: An unplanned interim analysis was performed because of the slow enrollment and publication of larger trials showing no benefit of the negative-pressure wound therapy. Of 411 eligible patients during the study period, 212 participants with class III obesity were enrolled. Of these, 110 underwent cesarean delivery and were subsequently randomized (55 to standard dressing and 55 to prophylactic negative-pressure wound therapy device). The primary outcome occurred in 29.1% in the standard surgical dressing compared with 20% in the negative-pressure wound therapy group (risk difference, 9.1%; 95% confidence interval, -8.3 to 25.8%; P=.38). The study was stopped early because of a low enrollment rate and lower likelihood of seeing a clinically significant benefit. CONCLUSION: The trial was stopped after an unplanned, interim analysis showed the use of a prophylactic negative-pressure wound therapy device used for cesarean delivery did not reduce wound complications compared with a standard surgical dressing.

Enhanced recovery after surgery protocols improve time to return to intended oncology treatment following interval cytoreductive surgery for advanced gynecologic cancers.

OBJECTIVE: The objective of this study was to determine whether the implementation of an enhanced recovery after surgery (ERAS) protocol is associated with earlier return to intended oncology treatment following interval cytoreductive surgery for advanced gynecologic cancers. METHODS: Participants comprised consecutive patients (n=278) with a preoperative diagnosis of stage IIIC or IV ovarian cancer, divided into those that received treatment before versus after implementation of an ERAS protocol at our institution. All patients received at least three cycles of neoadjuvant chemotherapy with a platinum based regimen and underwent interval cytoreduction via laparotomy with the intent to deliver additional cycles of chemotherapy postoperatively. The primary outcome was defined as the timely return to intended oncologic treatment, defined as the percentage of patients initiating adjuvant chemotherapy within 28 days postoperatively. RESULTS: The study cohorts included 150 pre-ERAS patients and 128 post-ERAS patients. Median age was 65 years (range 58-71). Most patients (211; 75.9%) had an American Society of Anesthesiologists score of 3, and the median operative time was 174 min (range 137-219). Median length of stay was 4 days (range 3-5 days) in the pre-ERAS cohort versus 3 days (range 3-4) in the post-ERAS cohort (p<0.0001). At 28 days after operation, 80% of patients had resumed chemotherapy in the post-ERAS cohort compared with 64% in the pre-ERAS cohort (odds ratio (OR) 2.29, 95% confidence interval (CI) 1.36 to 3.84; p=0.002). In multivariate logistic regression analysis, the ERAS protocol was the strongest predictor of timely return to intended oncology treatment (OR 10.18, 95% CI 5.35 to 20.32). CONCLUSION: An ERAS protocol for gynecologic oncology patients undergoing interval cytoreductive surgery is associated with earlier resumption of adjuvant chemotherapy.

Triaging abnormal cervical cancer screening tests using p16INK4a detection by ELISA on fresh cervical samples.

PROBLEM: Cervical cancer screening strategies in the United States include cotesting (human papillomavirus (HPV) with cytology), primary HPV with genotyping and reflex cytology, and cytology alone. An ongoing challenge is the appropriate triage of patients to colposcopy to those at highest risk. We investigated whether incorporation of p16INK4a immunodetection by enzyme-linked immunosorbent assay (ELISA) on fresh cervical samples obtained at the time of screening could improve appropriate referral to colposcopy. METHOD OF STUDY: A derivation group comprised of cervical swabs collected from subjects with high-grade dysplasia or cancer (positive control) and from subjects with negative screening history (negative control). Samples collected from colposcopy were used to evaluate the existing screening strategies individually and with incorporation of p16INK4a ELISA. Histology was used as the gold standard. RESULTS: Among 163 subjects recruited, 138 were included. In the derivation group, mean p16INK4a level was 2.86 ng/mL (n = 31) and 0.58 ng/mL (n = 20) among positive and negative controls respectively (p = 0.002) with an area under the receiver operator characteristic curve of 0.79 (p < 0.001). Among colposcopy subjects, sensitivity/specificity for cotesting, primary HPV, and cytology were 94%/42%, 88%/45%, and 88%/49%, respectively. Incorporation of p16INK4a resulted in similar sensitivity and improved specificity (cotesting+p16 88%/58%, primary HPV+p16 88%/57%, cytology+p16 81%/62%; p = 0.23/p = 0.008) with decrease in colposcopy referrals by 15% to 22% (p = 0.01). CONCLUSIONS: These results demonstrate the feasibility of quantifying p16INK4a by ELISA in fresh cervical samples, and its potential as an adjunct to existing screening strategies in the identification of high grade-dysplasia while reducing the number of colposcopic referrals.

Determining the Health State Utility Value of Urinary Tract Infection in Women.

OBJECTIVES: Health state utility values are a unique representation of an individual's valuation for being in a particular health state. Depending on the method of evaluation, group of patients, and setting, these values vary significantly. To date, majority of the available estimates for the health-related state utility values for urinary tract infection (UTI) has been in men with comorbid conditions such as benign prostatic hyperplasia and bladder cancer or with spinal cord abnormalities. The utility values in these studies ranged between 0.3 and 0.9. The purpose of this study was to determine and compare the health state utility value for UTI in women derived from EuroQol 5 dimensions (EQ-5D) questionnaire and visual analog scale (VAS) with the Standard Gamble (SG) interview in a tertiary medical center. METHODS: Healthy volunteers at least 18 years of age with no history of UTI were approached for study participation. Twenty-five subjects were given a standard sheet describing UTI and its symptoms and were asked to complete the EQ-5D and VAS followed by SG conversation. RESULTS: The median utility (interquartile range) for UTI varied based on the methods: EQ-5D, 1.00 (0.124); VAS, 0.98 (0.10); and SG, 0.90 (0.15). Spearman correlation showed that these values were weakly correlated. CONCLUSIONS: Our data suggest a value of 0.90 to represent the health state utility value of UTI in women older than 18 years. The EQ-5D is not sensitive to impact of UTI in women, and we would not recommend using it for that purpose based on our findings.