24-Hour Compared With 12-Hour Mifepristone-Misoprostol Interval for Second-Trimester Abortion: A Randomized Controlled Trial.

OBJECTIVE: To compare 24-hour and 12-hour mifepristone-to-misoprostol intervals for second-trimester medication abortion. METHODS: We conducted a prospective randomized controlled trial. Participants were allocated to receive mifepristone either 24 hours or 12 hours before misoprostol administration. The primary outcome was the time from the first misoprostol administration to abortion (induction time). Secondary outcomes included the time from mifepristone to abortion (total abortion time); fetal expulsion percentages at 12, 24, and 48 hours after the first misoprostol dose; side effects proportion; and pain and satisfaction scores. A sample size of 40 per group (N=80) was planned to compare the 24- and 12-hour regimens. RESULTS: Eighty patients were enrolled between July 2020 and June 2023, with 40 patients per group. Baseline characteristics were comparable between groups. Median induction time was 9.5 hours (95% CI, 10.3-17.8 hours) and 12.5 hours (95% CI, 13.5-20.2 hours) in the 24- and 12-hour interval arms, respectively ( P =.028). Median total abortion time was 33.0 hours (95% CI, 34.2-41.9 hours) and 24.5 hours (95% CI, 25.7-32.4 hours) in the 24- and 12-hour interval groups, respectively ( P <.001). At 12 hours from misoprostol administration, 25 patients (62.5%) in the 24-hour arm and 18 patients (45.0%) in the 12-hour arm completed abortion ( P =.178). At 24 hours from misoprostol administration, 36 patients (90.0%) in the 24-hour arm and 30 patients (75.0%) in the 12-hour arm had complete abortion ( P =.139). The need for additional medication or surgical treatment for uterine evacuation, pain scores, side effects, and satisfaction levels were not different between groups. CONCLUSION: A 24-hour mifepristone-to-misoprostol regimen for medication abortion in the second trimester provides a median 3-hour shorter induction time compared with the 12-hour interval. However, the median total abortion time was 8.5-hours longer in the 24-hour interval regimen. These findings can aid in shared decision making before medication abortion in the second trimester. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT04160221.

Obstetric and Early Neonatal Outcomes Following Second and Third COVID-19 Vaccination in Pregnancy.

BACKGROUND: Pregnant women are at higher risk for severe coronavirus disease 2019 (COVID-19). Since the release of the BNT162b2 messenger RNA vaccine (Pfizer/BioNTech), there has been accumulated data about the three vaccine doses. However, information regarding obstetric and neonatal outcomes of pregnant women vaccinated with the third (booster) vaccine is limited and primarily retrospective. OBJECTIVES: To evaluate the obstetric and early neonatal outcomes of pregnant women vaccinated during pregnancy with the COVID-19 booster vaccine compared to pregnant women vaccinated only by the first two doses. METHODS: We conducted a cross-sectional study of pregnant women who received the BNT162b2 vaccine during pregnancy. Obstetric and neonatal outcomes were compared between pregnant women who received only the first two doses of the vaccine to those who also received the booster dose. RESULTS: Overall, 139 pregnant women were vaccinated during pregnancy with the first two doses of the vaccine and 84 with the third dose. The third dose group received the vaccine earlier during their pregnancy compared to the two doses group (212 vs. 315 weeks, respectively, P < 0.001). No differences in obstetric and early neonatal outcomes between the groups were found except for lower rates of urgent cesarean delivery in the third dose group (adjusted odds ratio 0.21; 95% confidence interval 0.048-0.926, P = 0.039). CONCLUSIONS: Compared to the first two doses of the BNT162b2 vaccine given in pregnancy, the booster vaccination is safe and not associated with an increased rate of adverse obstetric and early neonatal outcomes.

Transient osteoporosis of the hip in pregnancy - a case series.

OBJECTIVE: Transient Osteoporosis of the Hip is a self-limiting disorder of severe hip joint pain presenting in pregnancy or postpartum, of which magnetic resonance imaging (MRI) is the modality of choice for diagnosis. Clinical data regarding transient osteoporosis of the hip is limited, precluding evidence-based decision-making such as recommended mode of delivery. In this case-series retrospective study, we aim to describe the natural course of transient osteoporosis of the hip during pregnancy and the postpartum period including implications of the mode of delivery. METHODS: All women diagnosed with unilateral/bilateral transient osteoporosis of the hip by MRI during pregnancy or postpartum between 2010 and 2019 at a single tertiary medical center were retrospectively studied. All MRI scans were reviewed by an experienced radiologist at the same single tertiary medical center. Data obtained from patients' electronic medical records and telephone questionnaires included maternal baseline characteristics, obstetric history, and current pregnancy obstetric and clinical outcome characteristics. Outcomes of normal vaginal delivery (NVD) and cesarean delivery (CD) were compared and analyzed. RESULTS: Thirty-four women were diagnosed with unilateral or bilateral transient osteoporosis of the hip during pregnancy (17 women) and postpartum (17 women). The mean maternal age was 34.18 ± 4.75 years. A family history of osteoporosis was reported in a rate of 29.4%. The rate of smokers was 47.1%, 32.4% of pregnancies were conceived by in-vitro fertilization (IVF), pre-pregnancy and term body mass index (BMI) were 22.03 and 27.6, respectively. No significant differences were found between NVD and CD in all parameters evaluated. Of 15 women with a sequential pregnancy, two were diagnosed with transient osteoporosis of the hip (13.3%). CONCLUSION: Women diagnosed with transient osteoporosis of the hip had advanced maternal age, low BMI, family history of osteoporosis, prevalent smoking and IVF pregnancies. Transient osteoporosis of the hip was bilateral in 25% and presented postpartum in 50% of cases. There was no significant difference in maternal outcomes between NVD and CD. Higher awareness of this potential diagnosis during pregnancy and postpartum may improve patient management and outcomes.

Predictive accuracy of the ABCD progression display among patients with keratoconus: A historic cohort analysis.

OBJECTIVE: To evaluate the accuracy of the ABCD Progression Display and the ABCD grading system in a population of adult patients with keratoconus. METHODS: A retrospective cohort analysis of all adult patients with keratoconus followed at the Shamir Medical Center between 2012 and 2017. A recommendation by the cornea specialist to undergo corneal crosslinking (CXL) was used as a surrogate of ectasia progression. The ABCD grading was not available to the treating physician and was computed post-hoc. Sensitivity and specificity of the ABCD Progression Display was calculated, and multivariate regression was used to estimate the risk to undergo CXL when the ABCD Progression Display indicated progression. The ABCD grading was compared between patients who required CXL to those who did not. A single eye of each patient was included. Sensitivity and specificity of the ABCD Progression Display were 82% and 73%, respectively. A multivariable model adjusted for possible confounders, found that ABCD Progression was associated with a 7-fold risk of undergoing CXL compared to a patient in whom progression was not recorded in the ABCD Progression Display (OR = 7.55; 95% CI = 3.82-14.93, p < 0.001). RESULTS: 293 eyes of 293 patients were analysed. Mean age at presentation was 26.92 ± 6.12 years. In 68 eyes, progression of keratoconus was recorded and CXL was performed (CXL-group). CONCLUSION: The ABCD Progression Display demonstrated adequate sensitivity and specificity and high predictive capabilities of keratoconus progression. It can be effectively utilized as an initial screening test in adults with keratoconus.

Maternal and Neonatal Immune Responses Following COVID-19 Infection and Vaccinations in Pregnancy.

The objective of the study was to compare the maternal and neonatal humoral immune responses among different groups of women, namely those vaccinated by the BNT162b2 vaccine, not vaccinated, and COVID-19-recovered parturient women at the time of delivery. This is a prospective cohort study of pregnant women, divided into four groups: Group A "Recovered"-recovered and not vaccinated. Group B "Second Vaccination"-first and second doses only. Group C "Third Vaccination"-third dose. Group D "No Third Vaccination"-women eligible for the third dose of the vaccine but did not receive it. Maternal and umbilical cord blood were sampled and tested for SARS-CoV-2 IgG antibodies on admittance to labor and immediately postpartum, respectively. Maternal serum SARS-CoV-2 IgG levels were significantly higher among Group C compared to Group B (741.6 (514.5-1069) vs. 333.5 (327-340.2), respectively). Both groups had higher antibody levels compared to Groups A and D (113.5 (61.62-209.1) and 57.99 (32.93-102.1), respectively). Similarly, umbilical cord blood SARS-CoV-2 IgG levels were also highest among Group C compared to the other three groups (1269 (953.4-1690) vs. Group B, 322.6 (305.6-340.5), Group A, 109 (49.01-242.6), and Group D, 103.9 (48.59-222), respectively). In conclusion, pregnant women who were fully vaccinated with three dosages before delivery generated the highest levels of maternal and neonatal SARS-CoV-2 IgG antibodies.

Early Adverse Events and Immune Response Following Second and Third COVID-19 Vaccination in Pregnancy.

(1) Background: The adverse-effect profile and short-term obstetric and neonatal outcomes among pregnant women who were vaccinated with the BNT162b2 vaccine at any stage of pregnancy do not indicate any safety concerns. The vaccine is effective in generating a humoral immune response in pregnant women. (2) Objective: To determine the vaccine-induced immunity and adverse events associated with the third (booster) dose of the BNT162b2 vaccine compared to the first and second dose of the vaccine among pregnant women. (3) Study design: A prospective cohort study in a tertiary referral center comparing pregnant women who were vaccinated by the first and second dose of the BNT162b2 (Pfizer/BioNTech) vaccine to pregnant women vaccinated by a third (booster) dose, between January and November 2021. A digital questionnaire regarding adverse events was filled by both groups 2−4 weeks after vaccination. Blood samples were collected and tested for SARS-COV-2 IgG antibodies 28−32 days after the administration of the second or third BNT162b2 dose. (4) Results: Seventy-eight pregnant women who received the first and second doses of the vaccine were compared to eighty-four pregnant women who received the third dose of the vaccine. In terms of adverse events following vaccination, local rash/pain/swelling (93.6% vs. 72.6%, p < 0.001) was significantly less common after the third vaccination compared to after the second vaccination. Other adverse events, including early obstetric complications, did not differ between the two groups. SARS-CoV-2 IgG serum levels 28−32 days after the vaccination were significantly higher after the third vaccination compared to the second vaccination (1333.75 vs. 2177.93, respectively, p < 0.001). (5) Conclusion: This study confirms the safety regarding early adverse events and immunogenicity, and the lack of early obstetric complications of the BNT162b2 second- and third-dose vaccine in pregnant women. The third (booster) dose is effective in generating a stronger humoral immune response in pregnant women compared with the second dose.

Metal Coordination Is Crucial for Geranylgeranyl Diphosphate Synthase-Bisphosphonate Interactions: A Crystallographic and Computational Analysis.

Geranylgeranyl diphosphate synthase (GGPPS) is a central metalloenzyme in the mevalonate pathway, crucial for the prenylation of small GTPases. As small GTPases are pivotal for cellular survival, GGPPS was highlighted as a potential target for treating human diseases, including solid and hematologic malignancies and parasitic infections. Most available GGPPS inhibitors are bisphosphonates, but the clinically available compounds demonstrate poor pharmacokinetic properties. Although the design of novel bisphosphonates with improved physicochemical properties is highly desirable, the structure of wild-type human GGPPS (hGGPPS) bound to a bisphosphonate has not been resolved. Moreover, various metal-bisphosphonate-binding stoichiometries were previously reported in structures of yeast GGPPS (yGGPPS), hampering computational drug design with metal-binding pharmacophores (MBP). In this study, we report the 2.2 Å crystal structure of hGGPPS in complex with ibandronate, clearly depicting the involvement of three Mg2+ ions in bisphosphonate-protein interactions. Using drug-binding assays and computational docking, we show that the assignment of three Mg2+ ions to the binding site of both hGGPPS and yGGPPS greatly improves the correlation between calculated binding energies and experimentally measured affinities. This work provides a structural basis for future rational design of additional MBP-harboring drugs targeting hGGPPS. SIGNIFICANCE STATEMENT: Bisphosphonates are inhibitors of geranylgeranyl diphosphate synthase (GGPPS), a metalloenzyme crucial for cell survival. Bisphosphonate binding depends on coordination by Mg2+ ions, but various Mg2+-bisphosphonate-binding stoichiometries were previously reported. In this study, we show that three Mg2+ ions are vital for drug binding and provide a structural basis for future computational design of GGPPS inhibitors.