Neratinib and Ado-Trastuzumab-Emtansine for Pre-treated and Untreated HER2-positive Breast Cancer Brain Metastases: Translational Breast Cancer Research Consortium Trial 022.

PURPOSE: Treatment options for HER2-positive breast cancer brain metastases (BCBM) remain limited. We previously reported central nervous system (CNS) activity for neratinib and neratinib-capecitabine. Preclinical data suggest that neratinib may overcome resistance to ado-trastuzumab-emtansine (T-DM1) when given in combination. In TBCRC 022's cohort 4, we examined the efficacy of neratinib plus T-DM1 in patients with HER2-positive BCBM. PATIENTS AND METHODS: In this multicenter, phase II study, patients with measurable HER2-positive BCBM received neratinib 160 mg daily plus T-DM1 3.6 mg/kg intravenously every 21 days in three parallel-enrolling cohorts (cohort 4A-previously untreated BCBM, cohorts 4B and 4C- BCBM progressing after local CNS-directed therapy without [4B] and with [4C] prior exposure to T-DM1). Cycle 1 diarrheal prophylaxis was required. The primary endpoint was the Response Assessment in Neuro-Oncology-Brain Metastases (RANO-BM) by cohort. Overall survival (OS) and toxicity were also assessed. RESULTS: Between 2018-2021, 6, 17, and 21 patients enrolled to cohorts 4A, 4B, and 4C. Enrollment was stopped prematurely for slow accrual. The CNS objective response rate in cohorts 4A, 4B, and 4C was 33.3% (95% confidence interval [CI]: 4.3-77.7%), 35.3% (95% CI: 14.2-61.7%), and 28.6% (95% CI: 11.3-52.2%), respectively; 38.1-50% experienced stable disease for ≥6 months or response. Diarrhea was the most common grade 3 toxicity (22.7%). Median OS was 30.2 months (cohort 4A; 95% CI: 21.9, not reached [NR]), 23.3 months (cohort 4B; 95% CI: 17.6, NR), and 20.9 months (cohort 4C; 95% CI: 14.9, NR). CONCLUSION: We observed Intracranial activity for neratinib plus T-DM1, including those with prior T-DM1 exposure, suggesting synergistic effects with neratinib. Our data provide additional evidence for neratinib-based combinations in patients with HER2-positive BCBM, even those who are heavily pre-treated.

A social-ecological examination of sleep among Airmen in technical training.

Inadequate sleep is an on-going risk to the health and mission readiness of U.S. Armed Forces, with estimates of sleep problems high above U.S. civilian populations. Intervening early in the career of active duty Air Force personnel (or "Airmen") with education and the establishment of healthy behaviors may prevent short and long term-detriments of sleep problems. This paper describes the results of a qualitative study seeking to understand the facilitators and barriers to achieving good sleep in a technical training school during the first year of entry into the United States Air Force. Using the social ecological framework and content analysis, three focus groups with Airmen were conducted to explore themes at the individual, social, environmental, and organizational/policy level. Overall, results indicated a cohort motivated to achieve good sleep, and also struggling with a number of barriers across each level. This paper highlights opportunities for population health interventions during technical training aimed at supporting Airmen in developing healthy sleep behaviors early in the course of their career.

The golden tickets: impact of preference signaling on obstetrics and gynecology residency applicants.

BACKGROUND: With the residency selection process becoming more competitive and programs receiving unprecedented numbers of applications, some specialties have introduced preference signaling in an attempt to help applicants target programs of interest. In the 2022-2023 application cycle, obstetrics and gynecology also introduced a 2-tiered system with a limited number of gold signals (n=3) and silver signals (n=15). OBJECTIVE: Given the novelty of preference signaling in the obstetrics and gynecology residency application process, this study aimed to (1) assess the effect of signals on interview offers and match and (2) discuss applicant attitudes toward this preference signaling system. STUDY DESIGN: This was a voluntary cross-sectional survey study conducted in April 2023 that was open to all fourth-year medical students who applied to an obstetrics and gynecology residency in the United States. Self-reported demographics, signaling, interview, and match data were collected. In addition, students were asked about attitudes toward signaling on a 5-point Likert scale. RESULTS: Of the 1507 applicants who entered an obstetrics and gynecology residency via match or Supplemental Offer and Acceptance Program process, 969 (64.3%) completed the survey. Moreover, an additional 22 applicants who did not match responded to the survey. More respondents used all 3 gold tokens (98.3%) and all 15 silver tokens (94.3%). The mean number of applications sent was 74.3±35.1, and the mean number of interviews received per applicant was 12.8±6.6. The interviews or token yields were 64.0%±31.5% for gold tokens, 43.8%±23.1% for silver tokens, and 9.8%±10.0% for no token. Of the survey respondents, 340/951 (35.8%) matched to a gold token program, 338/951 (35.5%) matched to a silver token program, and 244/951 (25.7%) matched to a nontoken program. Furthermore, 499/951 applicants (52.5%) reported feeling slightly positive or very positive about signaling. CONCLUSION: Most obstetrics and gynecology applicants in this survey participated in preference signaling. Gold and silver tokens were associated with high ratios of interview invitations compared with no token. However, the overall number of applications did not decrease in the 2022-2023 cycle, and only half of survey respondents reported feeling positive about the signaling process. These results can inform program directors and students about application number and strategy in upcoming cycles.

Does the Degree Matter? MD and DO Students Who Match Into OB/GYN Report Different Experiences in US Undergraduate Medical Education.

Background: Although allopathic (MD) and osteopathic (DO) students have similar curricular requirements, little is known about differences in MD and DO preparedness for obstetrics and gynecology (OB/GYN) residency. Objective: To assess differences in experiences and confidence of MD vs DO students who matched to OB/GYN. Methods: This cross-sectional survey study was open to all fourth-year medical students who matched to OB/GYN in the United States in April 2021. The survey included demographic data, clinical experiences, confidence (5-point sliding scale), and a 11-item knowledge test. Survey responses were compared to assess for disparities in experiences and confidence. Results: Survey response rate was 72.0% (1057 of 1469) students matched to OB/GYN postgraduate year 1 positions. Of the 871 MD and 175 DO responding students, MDs were more likely to have clerkships ≥6 weeks (78.1% vs 15.4%; P<.001) and a home sub-internship (92.0% vs 53.4%; P<.001). DOs reported more hands-on experiences with procedures (MD median=35 [20-35] vs DO median=40 [25-65]; P=.002). There was no difference in self-reported confidence in knowledge, technical skills, or having a realistic sense of internship, and no difference in baseline knowledge test scores. DOs felt less confident about their medical school preparation (aOR 0.40; 95% CI 0.25-0.66; P<.001) and were more likely to perceive inequity of residency preparation (aOR 1.88; 95% CI 1.18-3.00; P=.002). Conclusions: MD students matched to US OB/GYN residency programs reported longer clerkship and more home sub-internships, while DO students reported more hands-on experiences. Despite reporting similar confidence in knowledge and skills, DO students felt less prepared for internship.

The #ObGynInternChallenge: Reach, Adoption, Implementation, and Effectiveness of a Microlearning SMS-Distributed Curriculum.

PROBLEM: While many medical schools have implemented bootcamps or specialized curricula to prepare medical students for residency, these programs are neither universal nor consistent in their content. APPROACH: The authors created an electronic, multimodal, short messaging service (SMS)-distributed curriculum, called the #ObGynInternChallenge, to improve learners' medical knowledge, based on the Council on Resident Education in Obstetrics and Gynecology educational objectives. The curriculum was open to all fourth-year medical students who matched into obstetrics and gynecology (Ob/Gyn). Daily messages were delivered to participants' mobile devices via SMS for 25 consecutive weekdays, May 3-June 4, 2021. Each day's message included an introduction with key facts, an infographic, a website link with a podcast and additional reference materials, and at least one question. The authors assessed its reach, adoption, implementation, and effectiveness. OUTCOMES: For reach and adoption, total enrollment for the curriculum was 1,057 (72.0%) of 1,469 filled Ob/Gyn residency positions in the 2021 Match. The total cost of the intervention was $2,503.20 or $2.37 per participant. For implementation, all participants who signed up for the course received the daily messages, and 858/1,057 (81.2%) completed the course. Participants felt the curriculum was an excellent resource for studying (391/426, 91.8%) and the course was enjoyable to use (395/424, 93.2%). For effectiveness, mean score improvement was 11.6% (pre-test: 62.4%, post-test: 74.0%; P < .001). In the multivariate linear regression analysis, high podcast ( P = .02) and website use ( P = .002) were associated with greater score improvement. High social media use was associated with less improvement ( P = .02). NEXT STEPS: This study suggests promise for a low-cost, largely satisfying SMS-distributed curriculum in terms of offering some benefit for short-term knowledge gain. Next steps include expanding such a curriculum to meet standard learning objectives for all fourth-year medical students entering residency.

Reconsidering Race Adjustment in Prenatal Alpha-Fetoprotein Screening.

OBJECTIVE: Black racial designation is the only race for which adjustment is recommended for maternal prenatal serum alpha-fetoprotein (AFP) screening. The objective of this study is to reevaluate the relationship between maternal race and maternal serum AFP values in prenatal analyte screening. METHODS: This was a single-center retrospective analysis of patients who underwent prenatal analyte screening between January 2007 and December 2020. Nomograms for raw maternal serum AFP values by gestational age were created and compared between patients identified as "Black" and "non-Black" on the laboratory requisition. Multivariable linear regression models were created to evaluate the relationship among gestational age, maternal weight, and maternal race on maternal serum AFP levels. The new models were compared with the laboratory-derived calculations, which used historically determined race adjustments. RESULTS: A total of 43,997 patients underwent analyte screening, and 27,710 patients had complete data for analysis. Of these, 6% were identified as Black. Black patients had laboratory blood draws at a mean gestational age of 123 days, compared with 120 days in non-Black patients ( P <.001), and had higher maternal weight (mean 170 vs 161 lbs, P <.001). Nomograms for raw maternal serum AFP values did not differ between Black and non-Black patients ( P =.065). When adjusted for gestational age and maternal weight, no difference in maternal serum AFP values was identified between Black and non-Black individuals ( P =.81). CONCLUSION: No difference in maternal serum AFP values was identified between Black and non-Black pregnant individuals when adjusted by maternal weight and gestational age at blood draw. These findings suggest that routine race-based adjustment of maternal serum AFP screening should be discontinued.

Volume, Distribution, and Inequities by Race and Gender of Clinical Experiences Reported by Medical Students Entering Obstetrics and Gynecology Residencies.

OBJECTIVE: To assess for inequities by race and gender of fourth year medical students' (MS4s) self-reported clinical experience in obstetrics and gynecology (Ob/Gyn). DESIGN: This was a voluntary, cross-sectional survey. Participants provided demographic data, information regarding their preparation for residency, and self-reported numbers of hands-on clinical experiences. Responses were compared across demographic categories to assess for disparity in pre-residency experiences. SETTING: The survey was open to all MS4s matched to Ob/Gyn internships in the United States in 2021. PARTICIPANTS: The survey was distributed primarily via social media. Eligibility was verified by participants supplying the names of their medical school of origin and their matched residency program prior to completing the survey. 1057/1469 (71.9%) MS4s entering Ob/Gyn residencies participated. Respondent characteristics were not different from nationally available data. RESULTS: Median clinical experience numbers were calculated for hysterectomies (10; IQR 5-20), suturing opportunities (15; IQR 8-30), and vaginal deliveries (5.5; IQR 2-12). Non-White students had fewer hands-on experiences with hysterectomy, suturing, and cumulative clinical experiences when compared to White MS4s (p values <0.001). Female students had fewer hands-on experiences with hysterectomies (p < 0.04), vaginal delivery (p < 0.03), and cumulative experiences (p < 0.002) than male students. When assessed by quartiles, non-White students and female students were less likely to be in the top quartile for experience and more likely to be in the bottom quartile for experience than their White and male counterparts, respectively. CONCLUSIONS: A significant number of medical students entering Ob/Gyn residency have minimal hands-on clinical experience with foundational procedures. Additionally, there are racial and gender disparities in clinical experiences of MS4s matching to Ob/Gyn internships. Future work should identify how biases in medical education may affect the access to clinical experience in medical school, and potential interventions to mitigate inequities in procedures and confidence prior to residency.

Modeling gait score of broiler chicken via production and behavioral data.

Lameness in broilers may be associated with pain and is considered a major broiler production and welfare concern. Manual gait score assessment in commercial broiler houses is discrete, time-consuming, and laborious. As such, automatic methods for broiler gait score assessment are urgently needed. The objective of this study was to identify the relation of broiler gait score with several productions and behavioral metrics (bird BW, age, activity, and distribution), and establish three gait score prediction models for automatic gait score estimations in broiler farms with automatic weighing systems, camera systems, or both. Sixteen pens were used to rear Cobb 500 and Ross 708 broilers for eight and nine weeks, respectively (eight pens/strain, 12 birds/pen). The gait scores of all birds were assessed weekly by trained assessors following a six-point (0-5) scoring protocol from the third week. The pen's average BW was measured weekly. Top-view cameras were installed to continuously record videos of broilers in all 16 pens. Images were extracted from video clips (10 min/hour) during a 16-hour light period to determine the activity index and distribution index through image processing. The gait score was positively correlated with BW (R2 = 0.97 for Cobb and R2 = 0.96 for Ross), while negatively correlated with activity (R2 = 0.78 for Cobb and R2 = 0.73 for Ross). The three models showed high accuracies in predicting broiler gait score based on variables of BW, age, activity index, and distribution index (R2 = 0.90-0.91, RMSE = 0.38-0.41). The findings of this study demonstrated the potential of estimating broiler gait score using bird BW, age, activity index, and distribution index. This information will assist in the development of automated gait score assessment systems in broiler production.

Spacecraft sample collection and subsurface excavation of asteroid (101955) Bennu.

Carbonaceous asteroids, such as (101955) Bennu, preserve material from the early Solar System, including volatile compounds and organic molecules. We report spacecraft imaging and spectral data collected during and after retrieval of a sample from Bennu's surface. The sampling event mobilized rocks and dust into a debris plume, excavating a 9-meter-long elliptical crater. This exposed material is darker, spectrally redder, and more abundant in fine particulates than the original surface. The bulk density of the displaced subsurface material was 500 to 700 kilograms per cubic meter, which is about half that of the whole asteroid. Particulates that landed on instrument optics spectrally resemble aqueously altered carbonaceous meteorites. The spacecraft stored 250 ± 101 grams of material, which will be delivered to Earth in 2023.

Immediate reinforcement increased duration of time riding the stationary bicycle in children with autism spectrum disorder: a pilot study.

The necessity of promoting physical activity in individuals with Autism Spectrum Disorder (ASD) has been emphasized for decades. One of the barriers to participate in physical activity for individuals with ASD is limited interest and motivation. Therefore, understanding the motivation to exercise in this population is important. The objective was to determine the effect of using contingent reinforcement in the form of watching a preferred DVD to increase duration of time pedalling on a stationary bicycle within their predetermined target heart rate zone (THRZ) in children with ASD. Using a crossover design, seven participants (11 2.7 years) who were diagnosed with ASD were randomly assigned to either Group A or B. Time spent pedalling on a bicycle within the THRZ was analysed using a linear mixed-effect model with Bonferroni adjustments. The results showed that the DVD intervention motivated children with ASD to exercise for more than 10 minutes in moderate to vigorous physical activity compared to when they were exercising without watching a DVD. This result is significant as number of studies have revealed that 10 minutes of exercise could bring improvements in activities of daily living such as behaviors and academic performance in school.

Intramedullary, periosteal, and extraskeletal Ewing sarcomas: retrospective study of a series of 126 cases in a reference center.

OBJECTIVE: To evaluate the proportion of extraskeletal, periosteal, and intramedullary Ewing sarcomas among musculoskeletal Ewing sarcomas. MATERIAL AND METHOD: Our single-center retrospective study included patients with musculoskeletal Ewing sarcoma diagnosed between 2005 and 2019 in our pathology center (cases from our adult bone tumor referral center and adult and pediatric cases referred for review). Recurrences, metastases, and visceral Ewing sarcomas were excluded. Intramedullary Ewing sarcomas were defined by involvement of the medullary cavity. Periosteal cases were defined by involvement of the subperiosteal area without extension to the medullary cavity. Extraskeletal cases were defined by the absence of involvement of the bone tissue and the subperiosteal area. RESULTS: Our series included 126 patients with musculoskeletal Ewing sarcoma, including 118 skeletal Ewing sarcomas (93.7%) and 8 extraskeletal Ewing sarcomas (6.3%). Of the 118 skeletal Ewing sarcomas 112 were intramedullary (88.9%) and 6 were periosteal (4.8%). Extraskeletal Ewing sarcomas were more common in women and in patients older than 40 (p < 0.05). DISCUSSION: The 6.3% proportion of extraskeletal Ewing sarcoma is lower than the median of 30% estimated from the literature. This difference could be explained by an overestimation of extraskeletal Ewing sarcomas of the chest wall (Askin tumors), an underestimation of periosteal cases confused with extraskeletal cases, and the presence of "Ewing-like" soft tissue sarcomas in previous series. Because of its prognostic and therapeutic impact, the distinction of morphologic subtypes requires the cooperation of experienced radiologists and pathologists.

Does Use of a Feeding Protocol Change Outcomes in Gastroschisis? A Report from the Midwest Pediatric Surgery Consortium.

INTRODUCTION: Gastroschisis feeding practices vary. Standardized neonatal feeding protocols have been demonstrated to improve nutritional outcomes. We report outcomes of infants with gastroschisis that were fed with and without a protocol. MATERIALS AND METHODS: A retrospective study of neonates with uncomplicated gastroschisis at 11 children's hospitals from 2013 to 2016 was performed.Outcomes of infants fed via institutional-specific protocols were compared with those fed without a protocol. Subgroup analyses of protocol use with immediate versus delayed closure and with sutured versus sutureless closure were conducted. RESULTS: Among 315 neonates, protocol-based feeding was utilized in 204 (65%) while no feeding protocol was used in 111 (35%). There were less surgical site infections (SSI) in those fed with a protocol (7 vs. 16%, p = 0.019). There were no differences in TPN duration, time to initial oral intake, time to goal feeds, ventilator use, peripherally inserted central catheter line deep venous thromboses, or length of stay. Of those fed via protocol, less SSIs occurred in those who underwent sutured closure (9 vs. 19%, p = 0.026). Further analyses based on closure timing or closure method did not demonstrate any significant differences. CONCLUSION: Across this multi-institutional cohort of infants with uncomplicated gastroschisis, there were more SSIs in those fed without an institutional-based feeding protocol but no differences in other outcomes.

Immature teratoma in an adolescent with Proteus syndrome: A novel association.

Proteus syndrome (PS) is a complex disorder characterized by variable clinical findings of overgrowth and tumor susceptibility. This report presents the first known association between PS and an ovarian germ cell tumor in an adolescent with immature teratoma. A review of the diagnosis of PS and associated tumors is included.

Outcomes in gastroschisis: expectations in the postnatal period for simple vs complex gastroschisis.

OBJECTIVE: To provide generalizable estimates for expected outcomes of simple gastroschisis (SG) and complex gastroschisis (CG) patients from a large multi-institutional cohort for use during counseling. STUDY DESIGN: A retrospective study of 394 neonates with gastroschisis at 11 children's hospitals from January 2013 to March 2017 was performed. Analysis by Fisher's exact tests and Wilcoxon rank sum tests were performed. Outcomes of complex and simple gastroschisis are reported. RESULT: There were 315 (80%) SG and 79 (20%) CG. CG had increased time from birth to closure (6 vs 4.4 days), closure to goal feeds (69 vs 23 days), ventilator use (90% vs 73%), SSIs (31% vs 11%), NEC (14% vs 6%), PN use (71 vs 24 days), LOS (104.5 vs 33 days), and mortality (11% vs 0%). CONCLUSION: This study provides generalizable estimates for expected outcomes of patients with both SG and CG that can be utilized during counseling. CG has significantly worse in-hospital outcomes.

Pleuropulmonary Blastoma in Pediatric Lung Lesions.

BACKGROUND: Pediatric lung lesions are a group of mostly benign pulmonary anomalies with a broad spectrum of clinical disease and histopathology. Our objective was to evaluate the characteristics of children undergoing resection of a primary lung lesion and to identify preoperative risk factors for malignancy. METHODS: A retrospective cohort study was conducted by using an operative database of 521 primary lung lesions managed at 11 children's hospitals in the United States. Multivariable logistic regression was used to examine the relationship between preoperative characteristics and risk of malignancy, including pleuropulmonary blastoma (PPB). RESULTS: None of the 344 prenatally diagnosed lesions had malignant pathology (P < .0001). Among 177 children without a history of prenatal detection, 15 (8.7%) were classified as having a malignant tumor (type 1 PPB, n = 11; other PPB, n = 3; adenocarcinoma, n = 1) at a median age of 20.7 months (interquartile range, 7.9-58.1). Malignancy was associated with the DICER1 mutation in 8 (57%) PPB cases. No malignant lesion had a systemic feeding vessel (P = .0427). The sensitivity of preoperative chest computed tomography (CT) for detecting malignant pathology was 33.3% (95% confidence interval [CI]: 15.2-58.3). Multivariable logistic regression revealed that increased suspicion of malignancy by CT and bilateral disease were significant predictors of malignant pathology (odds ratios of 42.15 [95% CI, 7.43-340.3; P < .0001] and 42.03 [95% CI, 3.51-995.6; P = .0041], respectively). CONCLUSIONS: In pediatric lung masses initially diagnosed after birth, the risk of PPB approached 10%. These results strongly caution against routine nonoperative management in this patient population. DICER1 testing may be helpful given the poor sensitivity of CT for identifying malignant pathology.

Clinical outcomes following implementation of a management bundle for esophageal atresia with distal tracheoesophageal fistula.

BACKGROUND/PURPOSE: This study evaluated compliance with a multi-institutional quality improvement management protocol for Type-C esophageal atresia with distal tracheoesophageal fistula (EA/TEF). METHODS: Compliance and outcomes before and after implementation of a perioperative protocol bundle for infants undergoing Type-C EA/TEF repair were compared across 11 children's hospitals from 1/2016-1/2019. Bundle components included elimination of prosthetic material between tracheal and esophageal suture lines during repair, not leaving a transanastomotic tube at the conclusion of repair (NO-TUBE), obtaining an esophagram by postoperative-day-5, and discontinuing prophylactic antibiotics 24 h postoperatively. RESULTS: One-hundred seventy patients were included, 40% pre-protocol and 60% post-protocol. Bundle compliance increased 2.5-fold pre- to post-protocol from 17.6% to 44.1% (p < 0.001). After stratifying by institutional compliance with all bundle components, 43.5% of patients were treated at low-compliance centers (<20%), 43% at medium-compliance centers (20-80%), and 13.5% at high-compliance centers (>80%). Rates of esophageal leak, anastomotic stricture, and time to full feeds did not differ between pre- and post-protocol cohorts, though there was an inverse correlation between NO-TUBE compliance and stricture rate over time (ρ = -0.75, p = 0.029). CONCLUSIONS: Compliance with our multi-institutional management protocol increased 2.5-fold over the study period without compromising safety or time to feeds and does not support the use of transanastomotic tubes. LEVEL OF EVIDENCE: Level II. TYPE OF STUDY: Treatment Study.

CREOGs Over Coffee: Feasibility of an Ob-Gyn Medical Education Podcast by Residents.

BACKGROUND: Podcasts and other digital resources are increasingly popular among medical learners and allow the dissemination of research to larger audiences. Little is known about the feasibility of graduate medical education trainees developing podcasts for their own and others' learning. OBJECTIVE: We described the development and implementation of a medical education podcast series by residents for obstetrics and gynecology (Ob-Gyn) resident learning, and demonstrated feasibility, sustainability, and acceptance of this series. METHODS: We used the Council on Resident Education in Obstetrics and Gynecology (CREOG) educational guidelines to create a weekly study podcast for Ob-Gyn residents over 10 months. Costs and donations (for feasibility), downloads over time (for sustainability), and number of reviews on Apple iTunes and followers on Twitter (for acceptability) were measured. RESULTS: Sixty episodes were released from September 30, 2018, to July 28, 2019 (43 weeks). Initial costs included $3,150 startup and $29 monthly. Online donations through Patreon amounted to $200 a month, which covered 58% of startup costs at 10 months and are projected to cover full costs by 1.5 years. The podcast had 173 995 downloads as recorded through Podbean (39 a month in September, increased to 31 206 a month in July). It gained 644 followers on Twitter and 147 ratings on iTunes, with an average of 4.86 out of 5 stars. CONCLUSIONS: Medical podcasts created by Ob-Gyn residents during their training appear feasible and highly acceptable over a sustained period.