Pregnancy and birth outcomes after SARS-CoV-2 vaccination in pregnancy.

BACKGROUND: SARS-CoV-2 infection during pregnancy is associated with significant maternal morbidity and increased rates of preterm birth. For this reason, COVID-19 vaccination in pregnancy has been endorsed by multiple professional societies, including the American College of Obstetricians and Gynecologists and the Society for Maternal-Fetal Medicine, despite the exclusion of pregnant women from initial clinical trials of vaccine safety and efficacy. However, to date, little data exist regarding the outcomes of pregnant patients after COVID-19 vaccination. OBJECTIVE: To assess the safety and efficacy of COVID-19 vaccines in pregnant patients. STUDY DESIGN: A comprehensive vaccine registry was combined with a delivery database for an integrated healthcare system to create a delivery cohort that included vaccinated patients. Maternal sociodemographic data were examined to identify factors associated with COVID-19 vaccination. Pregnancy and birth outcomes were analyzed, including a composite measure of maternal and neonatal pregnancy complications, the Adverse Outcome Index. RESULTS: Of 2002 patients in the delivery cohort, 140 (7.0%) received a COVID-19 vaccine during pregnancy, and 212 (10.6%) experienced a COVID-19 infection during pregnancy. The median gestational age at first vaccination was 32 weeks (range, 13 6/7-40 4/7 weeks), and patients vaccinated during pregnancy were less likely than unvaccinated patients to experience COVID-19 infection before delivery (2/140 [1.4%] vs 210/1862 [11.3%]; P<.001). No maternal COVID-19 infection occurred after the vaccination of pregnant patients. Factors significantly associated with increased likelihood of vaccination in a multivariable logistic regression model included older age, higher level of maternal education, being a nonsmoker, use of infertility treatment for the current pregnancy, and lower gravidity. Compared with unvaccinated patients, no significant difference in the composite adverse outcome (7/140 [5.0%] vs 91/1862 [4.9%]; P=.95) or other maternal or neonatal complications, including thromboembolic events and preterm birth, was observed in vaccinated patients. CONCLUSION: In this birth cohort, vaccinated pregnant women were less likely than unvaccinated pregnant patients to experience COVID-19 infection, and COVID-19 vaccination during pregnancy was not associated with increased pregnancy or delivery complications. The cohort was skewed toward late pregnancy vaccination, and thus, findings may not be generalizable to vaccination during early pregnancy.

Factors influencing the adoption of the sentinel lymph node technique for endometrial cancer staging: an international survey of gynecologic oncologists.

OBJECTIVE: To explore the factors influencing adoption of the sentinel lymph node (SLN) technique for endometrial cancer staging among gynecologic oncologists. METHODS: A self-administered, web-based survey was sent via email (April 20 through May 21, 2017) to all members of European Society of Gynecologic Oncologists, International Gynecologic Cancer Society, and Society of Gynecologic Oncologists. Surgical and pathologic practices related to SLN and reasons for not adopting this technique were investigated. RESULTS: Overall, 489 attending physicians or consultants in gynecologic oncology from 69 countries responded: 201 (41.1%), 118 (24.1%), and 117 (23.9%) from Europe, the USA, and other countries, respectively (10.8% did not report a country). SLN was adopted by 246 (50.3%) respondents, with 93.1% injecting the cervix and 62.6 % using indocyanine green dye. The National Comprehensive Cancer Network SLN algorithm was followed by 160 (65.0%) respondents (USA 74.4%, Europe 55.4%, other countries 71.4%). However, 66.7% completed a backup lymphadenectomy in high-risk patients. When SLN biopsy revealed isolated tumor cells, 13.8% of respondents recommended adjuvant therapy. This percentage increased to 52% if micrometastases were detected. Among the 243 not adopting SLN, 50.2% cited lack of evidence and 45.3% stated that inadequate instrumentation fueled their decisions. CONCLUSIONS: SLN with a cervical injection is gaining widespread acceptance for staging of endometrial cancer among gynecologic oncologists worldwide. Standardization of the surgical approach with the National Comprehensive Care Network algorithm is applied by most users. Management of isolated tumor cells and the role of backup lymphadenectomy for 'high-risk' cases remain areas of investigation.

Prospective Outcomes of a Pelvic Floor Rehabilitation Program Including Vaginal Electrogalvanic Stimulation for Urinary, Defecatory, and Pelvic Pain Symptoms.

OBJECTIVES: This study evaluated our experience after implementing a pelvic floor rehabilitation program including behavioral modification, biofeedback, and vaginal electrogalvanic stimulation (EGS). METHODS: This prospective cohort study evaluated outcomes of patients with pelvic floor dysfunction (urinary or defecatory dysfunction, pelvic pain/dyspareunia) who underwent pelvic floor rehabilitation. Patients received 4 to 7 sessions (1 every 2 weeks) including biofeedback and concluded with 30 minutes of vaginal EGS. Surveys assessed subjective changes in symptoms; success was evaluated using a 10-point visual analog scale (VAS) at the final session (10 = most successful). Paired comparisons of responses at baseline and final treatment were evaluated. RESULTS: Ninety-four patients were followed up through therapy completion. Treatment indications included urinary (89.4%), defecatory (33.0%), and pelvic pain or dyspareunia (30.9%); 44.7% of patients had a combination of indications. Among women with urinary symptoms, the percentage reporting leakage decreased from 92.9% to 79.3% (P = 0.001), leakage at least daily decreased from 69.0% to 39.5% (P < 0.001), daily urgency with leakage decreased from 42.7% to 19.5% (P = 0.001), daily urgency without leakage decreased from 41.5% to 18.3% (P < 0.001), and median VAS rating (0 = not at all, 10 = a great deal) of daily life interference decreased from 5 to 1.5 (P < 0.001). The median success ratings were 8, 8, and 7 for treatment of urinary symptoms, pelvic pain/dyspareunia, and bowel symptoms, respectively. CONCLUSIONS: An aggressive pelvic rehabilitation program including biofeedback with vaginal EGS had a high rate of self-reported subjective success and satisfaction and should be considered a nonsurgical treatment option in patients with pelvic floor dysfunction.

Survival, Risk Factors, and Effect of Treatment in 101 Patients With Calciphylaxis.

OBJECTIVE: To report on the survival and the associations of treatments upon survival of patients with calciphylaxis seen at a single center. PATIENTS AND METHODS: Using the International Classification of Diseases, Ninth Revision diagnosis code of 275.49 and the keyword "calciphylaxis" in the dismissal narrative, we retrospectively identified 101 patients with calciphylaxis seen at our institution between January 1, 1999, through September 20, 2014, using a predefined, consensus-developed classification scheme. RESULTS: The average age of patients was 60 years: 81 (80.2%) were women; 68 (68.0%) were obese; 19 (18.8%) had stage 0 to 2 chronic kidney disease (CKD), 19 (18.9%) had stage 3 or 4 CKD; 63 (62.4%) had stage 5 or 5D (dialysis) CKD. Seventy-five patients died during follow-up. Six-month survival was 57%. Lack of surgical debridement was associated with insignificantly lower 6-month survival (hazard ratio [HR]=1.99; 95% CI, 0.96-4.15; P=.07) and significantly poorer survival for the entire duration of follow-up (HR=1.98; 95% CI, 1.15-3.41; P=.01), which was most pronounced in stage 5 or 5D CKD (HR=1.91; 95% CI, 1.03-3.56; P=.04). Among patients with stage 5/5D CKD, subtotal parathyroidectomy (performed only in patients with hyperparathyroidism) was associated with better 6-month (HR=0.12; 95% CI, 0.02-0.90; P=.04) and overall survival (HR= 0.37; 95% CI, 0.15-0.87; P=.02). CONCLUSION: Calciphylaxis is associated with a high mortality rate. Significantly effective treatments included surgical debridement and subtotal parathyroidectomy in patients with stage 5/5D CKD with hyperparathyroidism. Treatments with tissue-plasminogen activator, sodium thiosulfate, and hyperbaric oxygen therapy were not associated with higher mortality.

Cholecalciferol supplementation does not influence ß-cell function and insulin action in obese adolescents: a prospective double-blind randomized trial.

BACKGROUND: There is increasing interest in the extraskeletal effects of vitamin D, particularly in the obese state with regard to the development of insulin resistance and diabetes. OBJECTIVE: The objective of the study was to determine the effect of 2 doses of cholecalciferol (vitamin D3) supplementation on insulin action (Si) and pancreatic ß-cell function in obese adolescents. METHODS: We performed a 12-wk double-blind, randomized comparison of the effect of vitamin D3 supplementation on Si and ß-cell function in obese Caucasian adolescents (body mass index > 95(th) percentile). The subjects were randomly assigned to receive either 400 IU/d (n = 25) or 2000 IU/d (n = 26) of vitamin D3. Each subject underwent a 7-sample 75 g oral glucose tolerance test, with glucose, insulin, and C-peptide measurements, to calculate Si and ß-cell function as assessed by the disposition index (DI), with use of the oral minimal model before and after supplementation. A total of 51 subjects aged 15.0 ± 1.9 y were enrolled. Included for analysis at follow-up were a total of 46 subjects (20 male and 26 female adolescents), 23 in each group. RESULTS: Initial serum 25-hydroxyvitamin D [25(OH)D] was 24.0 ± 8.1 µg/L. There was no correlation between 25(OH)D concentrations and Si or DI. There was a modest but significant increase in 25(OH)D concentration in the 2000 IU/d group (3.1 ± 6.5 µg/L, P = 0.04) but not in the 400 IU/d group (P = 0.39). There was no change in Si or DI following vitamin D3 supplementation in either of the treatment groups (all P > 0.10). CONCLUSIONS: The current study shows no effect from vitamin D3 supplementation, irrespective of its dose, on ß-cell function or insulin action in obese nondiabetic adolescents with relatively good vitamin D status. Whether obese adolescents with vitamin D deficiency and impaired glucose metabolism would respond differently to vitamin D3 supplementation remains unclear and warrants further studies. This trial was registered at clinicaltrials.gov as NCT00858247.

Dietary docosahexaenoic acid supplementation in children with autism.

OBJECTIVE: The aim of the study was to determine whether docosahexaenoic acid (DHA) supplementation improves the behavior of children with autism. METHODS: A group of 3- to 10-year-old children with autism were randomized in a double-blind fashion to receive a supplement containing 200 mg of DHA or a placebo for 6 months. The parents and the investigator completed the Clinical Global Impressions-Improvement scale to rate changes in core symptoms of autism after 3 and 6 months. The parents completed the Child Development Inventory and the Aberrant Behavior Checklist, and both parents and teachers completed the Behavior Assessment Scale for Children (BASC) at enrollment and after 6 months. RESULTS: A total of 48 children (40 [83%] boys, mean age [standard deviation] 6.1 [2.0] years) were enrolled; 24 received DHA and 24 placebo. Despite a median 431% increase in total plasma DHA levels after 6 months, the DHA group was not rated as improved in core symptoms of autism compared to the placebo group on the CGI-I. Based on the analysis of covariance models adjusted for the baseline rating scores, parents (but not teachers) provided a higher average rating of social skills on the BASC for the children in the placebo group compared to the DHA group (P = 0.04), and teachers (but not parents) provided a higher average rating of functional communication on the BASC for the children in the DHA group compared to the placebo group (P = 0.02). CONCLUSIONS: Dietary DHA supplementation of 200 mg/day for 6 months does not improve the core symptoms of autism. Our results may have been limited by inadequate sample size.

Cystathionine beta-synthase (CBS) contributes to advanced ovarian cancer progression and drug resistance.

BACKGROUND: Epithelial ovarian cancer is the leading cause of gynecologic cancer deaths. Most patients respond initially to platinum-based chemotherapy after surgical debulking, however relapse is very common and ultimately platinum resistance emerges. Understanding the mechanism of tumor growth, metastasis and drug resistant relapse will profoundly impact the therapeutic management of ovarian cancer. METHODS/PRINCIPAL FINDINGS: Using patient tissue microarray (TMA), in vitro and in vivo studies we report a role of of cystathionine-beta-synthase (CBS), a sulfur metabolism enzyme in ovarian carcinoma. We report here that the expression of cystathionine-beta-synthase (CBS), a sulfur metabolism enzyme, is common in primary serous ovarian carcinoma. The in vitro effects of CBS silencing can be reversed by exogenous supplementation with the GSH and H2S producing chemical Na2S. Silencing CBS in a cisplatin resistant orthotopic model in vivo by nanoliposomal delivery of CBS siRNA inhibits tumor growth, reduces nodule formation and sensitizes ovarian cancer cells to cisplatin. The effects were further corroborated by immunohistochemistry that demonstrates a reduction of H&E, Ki-67 and CD31 positive cells in si-RNA treated as compared to scrambled-RNA treated animals. Furthermore, CBS also regulates bioenergetics of ovarian cancer cells by regulating mitochondrial ROS production, oxygen consumption and ATP generation. This study reports an important role of CBS in promoting ovarian tumor growth and maintaining drug resistant phenotype by controlling cellular redox behavior and regulating mitochondrial bioenergetics. CONCLUSION: The present investigation highlights CBS as a potential therapeutic target in relapsed and platinum resistant ovarian cancer.

Retrospective analysis of tissue plasminogen activator as an adjuvant treatment for calciphylaxis.

OBJECTIVE: To report our experience with low-dose tissue plasminogen activator in the treatment of calciphylaxis, a rare, usually fatal thrombotic condition that results in ischemia, necrosis, and infarction of adipose and cutaneous tissue. DESIGN: Retrospective chart review. SETTING: Tertiary care academic medical center. PATIENTS: Fifteen patients (4 men and 11 women) with calciphylaxis, treated from January 1, 2002, through December 31, 2010. INTERVENTION: Treatment with tissue plasminogen activator, concomitant wound care, and management of calcium-phosphate status. MAIN OUTCOME MEASURES: Short-term ulcer healing, long-term survival. RESULTS: Patients received daily low-dose infusions of tissue plasminogen activator (mean treatment duration, 11 days). Six patients had no adverse reactions, 3 had minor bleeding, 6 required blood transfusions, and 3 had life-threatening bleeding. No patients died of treatment-related complications. Ten patients died (median time to death, 3.6 months; range, 23 days to 4.2 years). Of the remaining 5 patients, the median duration of follow-up was 36.8 months (range, 70 days to 4.3 years). Patients treated with tissue plasminogen activator had approximately 30% greater survival than controls, but the difference was not significant (P= .14). Our results were limited by the use of concomitant therapies, referral bias for advanced disease, and retrospective case-series design. CONCLUSIONS: Thrombolytic tissue plasminogen activator may be a useful adjunctive treatment in the management of patients with calciphylaxis. However, a multidisciplinary approach that includes aggressive wound care, débridement, thrombolytic therapy, restoration of tissue oxygenation, avoidance of infection, and control of calcium-phosphate homeostasis also is essential.

Assessing adherence to evidence-based guidelines for the diagnosis and management of uncomplicated urinary tract infection.

OBJECTIVE: To assess adherence to evidence-based guidelines for the diagnosis and management of uncomplicated urinary tract infection (UTI) in a family medicine residency clinic setting. PATIENTS AND METHODS: We retrospectively reviewed the medical records of female patients seen in 2005 at the Mayo Clinic Family Medicine Center in Scottsdale, Ariz, who were identified by International Classification of Diseases, Ninth Revision code 599.0 (UTI). We assessed documentation rates, use of diagnostic studies, and antibiotic treatments. Antibiotic sensitivity patterns from outpatient urine culture and sensitivity analyses were determined. RESULTS: Of 228 patients, 68 (30%) had uncomplicated UTI. Our physicians recorded essential history and examination findings for most patients. Documentation of the risk of sexually transmitted disease differed between residents and attending physicians and was affected by patient age. Urine dipstick and urine culture and sensitivity analyses were ordered in 57 (84%) and 52 (76%) patients, respectively. Eighty percent of patients with positive results on urine dipstick analyses also had urine culture and sensitivity analyses. Sulfamethoxazole-trimethoprim (SMX-TMP) was used as initial therapy in 26 patients (38%). Sixty-one percent of SMX-TMP and ciprofloxacin prescriptions were appropriately provided for 3 days. Escherichia coil was sensitive to SMX-TMP in 33 (94%) of 35 cultures. Treatment was not changed in any patient with an uncomplicated UTI because of results of urine culture and sensitivity analyses. Antibiotic sensitivity patterns for outpatients were significantly different from those for inpatients. CONCLUSION: Only 30% of our patients had uncomplicated UTI, making their management within clinical guidelines appropriate. However, of those patients with uncomplicated UTI, less than 25% received empirical treatment as suggested. Urine culture and sensitivity analyses were performed frequently, even in patients who already had positive results on a urine dip-stick analysis. Although SMX-TMP is effective, it is underused. On the basis of these findings, we hope to provide interventions to increase SMX-TMP prescription, decrease use of urine culture and sensitivity analyses, and increase the frequency of 3-day antibiotic treatments at our institution.