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Background: Single-agent immune checkpoint inhibitors (ICIs) have demonstrated limited responses in recurrent ovarian cancer; however, 30%-40% of patients achieve stable disease. The primary objective was to estimate progression-free survival (PFS) after sequential versus combination cytotoxic T-lymphocyte antigen 4 and programmed death ligand 1 ICIs in patients with platinum-resistant high-grade serous ovarian cancer (HGSOC)., Methods: Patients were randomized to a sequential arm (tremelimumab followed by durvalumab on progression) or a combination arm (tremelimumab plus durvalumab, followed by durvalumab) via a Bayesian adaptive design that made it more likely for patients to be randomized to the more effective arm. The primary end point was immune-related PFS (irPFS)., Results: Sixty-one subjects were randomized to sequential (n = 38) or combination therapy (n = 23). Thirteen patients (34.2%) in the sequential arm received durvalumab. There was no difference in PFS in the sequential arm (1.84 months; 95% CI, 1.77-2.17 months) compared with the combination arm (1.87 months; 95% CI, 1.77-2.43 months) (p = .402). In the sequential arm, no responses were observed, although 12 patients (31.6%) demonstrated stable disease. In the combination arm, two patients (8.7%) had partial response, whereas one patient (4.4%) had stable disease. Adverse events were consistent with those previously reported for ICIs. Patient-reported outcomes were similar in both arms., Conclusions: There was no difference in irPFS for combination tremelimumab plus durvalumab compared to tremelimumab alone (administered as part of a sequential treatment strategy) in a heavily pretreated population of patients with platinum-resistant HGSOC. Response rates were comparable to prior reports, although the combination regimen did not add significant benefit, as has been previously described., (© 2023 American Cancer Society.)

Introduction: Children exposed to parental intimate partner violence and abuse, mental illness, and substance use experience a range of problems which may persist into adulthood. These risks often co-occur and interact with structural factors such as poverty. Despite increasing evidence, it remains unclear how best to improve outcomes for children and families experiencing these adversities and address the complex issues they face., Aims and Methods: Systematic review of systematic reviews. We searched international literature databases for systematic reviews, from inception to 2021, to provide an evidence overview of the range and effectiveness of interventions to support children and families where these parental risk factors had been identified., Results: Sixty-two systematic reviews were included. The majority ( n  = 59) focused on interventions designed to address single risk factors. Reviews mostly focused on parental mental health ( n  = 38) and included psychological interventions or parenting-training for mothers. Only two reviews assessed interventions to address all three risk factors in combination and assessed structural interventions. Evidence indicates that families affected by parental mental health problems may be best served by integrated interventions combining therapeutic interventions for parents with parent skills training. Upstream interventions such as income supplementation and welfare reform were demonstrated to reduce the impacts of family adversity., Conclusion: Most intervention approaches focus on mitigating individual psychological harms and seek to address risk factors in isolation, which presents potentially significant gaps in intervention evidence. These interventions may not address the cumulative impacts of co-occurring risks, or social factors that may compound adversities., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objective: To determine whether peak estradiol (E 2 ) levels above the usual physiologic range (300-500 pg/mL) will impact programmed frozen embryo transfer (FET) outcomes in an ideal study population of those using good-quality single euploid blastocysts., Design: Retrospective cohort study., Setting: University-based clinic., Patients: Single euploid-programmed FET done at a single academic institution from January 2016 to December 2019. The population was divided into three groups on the basis of peak serum E 2 levels during endometrial preparation: group A (E 2 <300 pg/mL), group B (300-500 pg/mL), and group C (>500 pg/mL). Group B was used as the reference range for statistical analysis., Intervention: Frozen embryo transfer cycles., Main Outcome Measures: The primary outcome was the live birth rate (LBR). Secondary outcomes included implantation, biochemical, ectopic, and miscarriage rates., Results: A total of 750 FET cycles were included in this study. Poisson regression analysis showed a negative impact of higher peak E 2 on the LBR. A decrease in LBR was noted between group C and referent group B (50.2% vs. 63.4%, risk ratio 0.79 [0.68-0.91]) and group A and referent group B (42.5% vs. 63.4%, risk ratio 0.67 [0.46-0.98]). Secondary outcomes were notable for a lower implantation rate when groups A and C were compared with group B and a higher biochemical rate between group C and group B. There was no notable difference between groups in ectopic or miscarriage rates., Conclusion: Limiting peak serum E 2 levels to 300-500 pg/mL during programmed FET cycles is associated with improved LBRs compared with cycles with peak E 2 levels of <300 pg/mL or >500 pg/mL in an ideal study population., Competing Interests: Declaration of interests N.V. has nothing to disclose. N.A. has nothing to disclose. S.D.S. has nothing to disclose., (Copyright © 2023 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: Due to previously reported trastuzumab safety concerns and the scant data available in endometrial cancer patients, we sought to assess the safety, tolerability and toxicity profile of trastuzumab in patients with advanced/recurrent uterine serous carcinoma (USC) that overexpress HER2/neu in our multicenter randomized phase II trial., Methods: Patients were randomized 1:1 to receive carboplatin/paclitaxel (C/P) for 6 cycles ± trastuzumab (T) with the experimental arm continuing to receive single agent trastuzumab maintenance treatment until disease progression/toxicity. Progression-free-survival was the primary endpoint; overall-survival and toxicity were secondary endpoints. Adverse events (AEs) were compared between treatment arms., Results: There were 28 patients in the C/P arm and 32 patients in the experimental (C/P + T) arm. Fifty-eight patients (97%) experienced 977 treatment-related AEs of which 875 (89.6%) were low-grade (grade 1-2) and 102 (10.4%) were high-grade (grade 3-5). The mean ± standard deviation of AEs per patient was 15.5 ± 16.3 in the C/P arm and 17.0 ± 16.0 in the C/P + T arm. Gastrointestinal AEs were the most common in both arms (n = 155, 15.7%) of which 94.2% were low-grade (n = 146). Importantly, no significant difference between treatment arms was detected in any system-organ class of AE including cardiac AE. Five (17%) of 29 patients who received prolonged trastuzumab maintenance therapy had no sign of cumulative toxicity after an average (range) of 5.1 (4.2-6.3) years., Conclusions: Trastuzumab appears to be safe and has a manageable toxicity profile both when used in combination with chemotherapy and when used for single agent maintenance in patients with HER2/neu positive USC. This safety profile is reassuring given the proven efficacy of trastuzumab in advanced/recurrent HER2/neu positive USC., Competing Interests: Declaration of Competing Interest All authors fulfill the conditions required for authorship., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background and Objectives: Risky sexual behavior among adolescents is a public health crisis. We describe a novel approach to sexual health education where medical students manage a curriculum for an entire seventh grade in one Rhode Island city to better equip students with comprehensive knowledge about sexual health., Methods: Medical students were trained to teach 12 sessions to seventh-grade students under the supervision of the classroom teacher using a curriculum designed by medical students and faculty (modeled on the Family Life and Sexual Health [FLASH] curriculum but tailored to meet the community's needs). Pre- and postassessment surveys were conducted during the 2015-2016 academic year. We analyzed survey data collected pre- and postprogram using IBM SPSS Statistics., Results: Pre and postassessments were completed by 62% of students (74/120). Students completing the curriculum scored 8% higher on the postassessment vs the preassessment, (70.4% vs 62.32%, absolute difference=8.11%, P<0.001). Student knowledge improved in domains of pregnancy prevention, reproductive system/anatomy, general knowledge and prevention of sexually transmitted infections (STIs), safe sex practices, sexual assault, and sexual decision making. Respondents' perception of the importance of school-based sexual health lessons as well as their willingness to discuss sexual issues with an adult increased after completing the program., Conclusions: A year-long, middle school-based sexual health program taught by medical students showed significant improvements in sexual health knowledge and increased willingness to engage in dialogue about sex with trusted adults. Adolescents may benefit from long-term interaction and instruction about sexual education from medical students.

Background: School-based programs are important in addressing risky teenage sexual behavior. We implemented a sex education program using trained medical student volunteers., Methods: Medical students (n=30) implemented a seven-session curriculum, designed by medical students and faculty, to 7th and 8th grade students (n=310) at a local school. Middle school students completed pre- and post-assessments. Teachers and medical students completed questionnaires relating their perceptions of students' attitudes and understanding of sexual health., Results: Students completing the curriculum scored 5% higher on post- versus pre-assessment (84% vs 78.7%, p<0.001). Statistically significant gains were noted in knowledge of reproductive system anatomy, community resources, and sexual decision making. Sixty percent of middle school teachers compared to only 16.7% of medical student volunteers reported discomfort teaching sexual health., Discussion: Sexual education delivered by trained medical student volunteers may improve middle schoolers' understanding of sexual health. [Full article available at http://rimed.org/rimedicaljournal-2017-01.asp].

It is important for surgeons to understand patients' expectations for surgery. We asked whether patient factors and preoperative functional outcome scores reflect the degree of expectations patients have for posterior spinal surgery. Second, we asked whether patients' expectations for surgery predict improvements in functional outcome scores after surgery. We prospectively enrolled 155 consecutive surgical patients with greater than 90% followup. Patients' expectations were evaluated preoperatively along with SF-36 and Oswestry disability questionnaires. Postoperatively (6 months for decompression; 1 year for fusions), we quantified patient-derived satisfaction regarding whether expectations were met and by patient-derived functional outcome scores. In patients undergoing decompression, gender, SF-36 general health domain, and SF-36 physical component score predicted patients with high expectations for surgery. Patients with high expectations also reported greater postoperative improvements in SF-36 role physical domain scores after surgery. Expectations for surgery were met in 81% of patients. In a subset of patients (21 of 143), expectations were not met. These patients reported lower mean preoperative SF-36 general health, vitality, and mean mental component scores.

Objective: Functional outcomes of neurologically intact patients with burst fractures may be dependent on final kyphosis at the end of treatment. Conservative treatment is indicated if an acceptable sagittal alignment of the spine can be anticipated. Thoracolumbar burst fractures are often grouped as a single entity where, in fact, anatomically distinct areas of the spine may behave differently owing to different biomechanical factors. The goal of this work was to evaluate differential behavior in terms of final kyphosis in anatomically distinct regions of the spine following stable burst fractures., Methods: Prospective analysis of kyphosis in 60 patients treated conservatively for traumatic thoracolumbar burst fracture was conducted. Initial trauma supine radiographs were measured for initial kyphosis (Ki). Final kyphosis (Kf) in the upright patient was measured at the end of treatment. The Ki and Kf were plotted on a scatter graph; with use of linear regression analysis, a mathematical model was created to define a relationship between Ki and Kf based on anatomic level of the spine., Results: The thoracolumbar spine behaved in two independent patterns with respect to Kf. Kf at the thoracolumbar junction (T11-L1) had a collapse pattern that could be approximated most accurately with the equation Kf = Ki + 0.5 Ki. At the midlumbar spine, L2-L3 level, a best-fit model for collapse was Kf = Ki + 4 degrees ., Conclusion: In this cohort of patients, fractures that were categorized as "stable" and not requiring surgery were studied for the purpose of determining differential collapse patterns in anatomically distinct areas of the lumbar spine. We have demonstrated that the thoracolumbar junction and the midlumbar spine behave differently biomechanically and recommend that these two anatomic levels be studied independently for research purposes.