Academic performance in moderately and late preterm children in the United States: are they catching up?

OBJECTIVE: To determine whether preterm birth of 32-36 6/7 weeks gestation affected school performance from kindergarten through fifth grade. STUDY DESIGN: We assessed 14350 term infants and 1195 32-36 6/7 weeks gestation infants followed in the Early Childhood Longitudinal Study Kindergarten 2011 cohort for classroom performance in kindergarten-fifth grade. Multivariable regression was performed for comparisons, and data were weighted to be representative of the US population. RESULTS: Children born 35-36 6/7 weeks gestation had no significant difference in their academic scores or performance, while 32-34 6/7 weeks' children had lower academic scores and teacher performance scores when compared to term children. Children born between 32 and 36 6/7 weeks gestation had higher odds of individualized education plan needs and had learning disability diagnoses compared to term children. CONCLUSIONS: Children born between 32 and 34 6/7 weeks gestation have poor school performance compared to term children. Children born between 32 and 36 6/7 weeks gestation are at risk for learning disabilities and likely benefit from continued support and services to improve achievement throughout school.

A Case of an Obstructed Delivery by a Large, Lower Uterine Segment Fibroid Interlocked with a Fetal Mentum.

Uterine leiomyomata are associated with many pregnancy complications and will likely become increasingly common as the average age of childbearing increases. We describe a case of an obstructed delivery by a large fibroid. A 37-year-old G2P1001 with a 10-cm anterior, lower uterine segment fibroid presented for labor induction. Labor was complicated by arrest of descent due to suspected obstruction of the fetal body by the fibroid after descent of the fetal head, and delivery during cesarean section was complicated by apparent interlocking of the fetal mentum with the fibroid. Large, anterior lower uterine segment fibroids have the potential to obstruct delivery of the fetal head or of the fetal body, and these patients should be counseled regarding the potential for complications via both vaginal and cesarean deliveries.

Red Blood Cell Transfusion in Patients With Placenta Accreta Spectrum: A Systematic Review and Meta-analysis.

OBJECTIVE: To evaluate red blood cell use during delivery in patients with placenta accreta spectrum. DATA SOURCES: We searched MEDLINE, EMBASE, CINAHL, Cochrane Central, ClinicalTrials.gov, and Scopus for clinical trials and observational studies published between 2000 and 2021 in countries with developed economies. METHODS OF STUDY SELECTION: Abstracts (n=4,275) and full-text studies (n=599) were identified and reviewed by two independent reviewers. Data on transfused red blood cells were included from studies reporting means and SDs, medians with interquartile ranges, or individual patient data. The primary outcome was the weighted mean number of units of red blood cells transfused per patient. Between-study heterogeneity was assessed with an I2 statistic. Secondary analyses included red blood cell usage by placenta accreta subtype. TABULATION, INTEGRATION, AND RESULTS: Of the 599 full-text studies identified, 20 met criteria for inclusion in the systematic review, comprising 1,091 cases of placenta accreta spectrum. The number of units of red blood cells transfused was inconsistently described across studies, with five studies (25.0%) reporting means, 11 (55.0%) reporting medians, and four (20.0%) reporting individual patient data. The weighted mean number of units transfused was 5.19 (95% CI 4.12-6.26) per patient. Heterogeneity was high across studies (I2=91%). In a sensitivity analysis of five studies reporting mean data, the mean number of units transfused was 6.61 (95% CI 4.73-8.48; n=220 patients). Further quantification of units transfused by placenta accreta subtype was limited due to methodologic inconsistencies between studies and small cohort sizes. CONCLUSION: Based on the upper limit of the CI in our main analysis and the high study heterogeneity, we recommend that a minimum of 6 units of red blood cells be available before delivery for patients with placenta accreta spectrum. These findings may inform future guidelines for predelivery blood ordering and transfusion support. SYSTEMATIC REVIEW REGISTRATION: PROSPERO, CRD42021240993.

Fasting Compared With Fed and Oral Intake Before the 1-Hour Oral Glucose Tolerance Test: A Randomized Controlled Trial.

OBJECTIVE: To evaluate the effect of fasting compared with eating before the 1-hour oral glucose tolerance test (OGTT) on gestational diabetes mellitus (GDM) screening results. METHODS: In a single-center, prospective randomized trial, participants were randomized to: 1) fasting for 6 or more hours or 2) oral intake ("fed") within 2 hours of the 50-g, 1-hour OGTT. The 1-hour OGTT was administered after 24 weeks of gestation. A positive screen result was defined as a serum glucose level of 140 mg/dL or higher. Protocol adherence was assessed by a survey administered immediately after the OGTT. We planned to enroll 100 participants in each group to detect an absolute difference of 20 percentage points or more on the 1-hour OGTT screen-positive rate using Fisher exact test, assuming an estimated screen-positive rate of 45% in the fasting and 25% in the fed group and 10% attrition, with a two-sided α=0.05, power=0.8. The primary outcome was the 1-hour OGTT screen-positive rate. Secondary outcomes included mean 1-hour OGTT glucose values, GDM diagnosis, maternal and neonatal outcomes, and patient perceptions regarding the 1-hour OGTT. RESULTS: From November 2020 through April 2021, 200 participants were randomized. One hundred ninety-five completed the 1-hour OGTT (97 fasting, 98 fed). Participant surveys confirmed 97.9% (n=95) adherence to the fasting and 91.8% (n=90) adherence to the fed groups. The screen-positive rate was significantly higher in the fasting than the fed group (32.0% vs 13.3%, respectively, P=.002), as was the mean glucose value (127.7 mg/dL vs 113.3 mg/dL, P=.002). The incidence of GDM in the fasting group was 12.4% (n=12) and in the fed group was 5.1% (n=5) (P=.08). There were no significant differences in maternal or neonatal outcomes. CONCLUSION: Fasting for 6 or more hours doubled the incidence of a positive 1-hour OGTT result when compared with eating within 2 hours of the test. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT04547023.

Clinical factors associated with a positive postpartum depression screen in people with cardiac disease during pregnancy.

Background: While people with cardiac disease are known to be at increased lifetime risk of depression, little is known about postpartum depression rates in this population. Describing rates of positive postpartum depression screens and identifying risk factors that are unique to cardiac patients may help inform risk reduction strategies. Methods: This retrospective cohort study included pregnant patients with congenital and/or acquired cardiac disease who delivered at a single institution between 2014 and 2020. The primary outcome was a positive postpartum depression screen, defined as Edinburgh Postpartum Depression Score (EPDS) ≥10. Potential exposures were selected a priori and compared between patients with and without a positive postpartum depression screen using Wilcoxon rank-sum and Fisher's exact tests. Secondary outcomes were responses to a longitudinal follow-up survey sent to English-speaking patients evaluating cardiac status, mental health, and infant development. Results: Of 126 eligible cardiac patients, 23 (18.3%) had a positive postpartum depression screen. Patients with a positive postpartum depression screen were more likely to have had antepartum anticoagulation with heparin or enoxaparin (56.5% versus 26.2%, p=0.007), blood transfusion during delivery (8.7% versus 0%, p=0.032), and maternal-infant separation postpartum (52.2% versus 28.2%, p=0.047) compared to patients with a negative screen. Among 29 patients with a positive screen who responded to the follow up survey, 50% reported being formally diagnosed with anxiety or depression and 33.3% reported child development problems. Conclusions: Our results highlight the importance of screening for postpartum depression in patients with cardiac disease, especially those requiring antepartum anticoagulation or maternal-infant separation postpartum.

Genome Characterization of Gordonia Phage Amore2.

Novel Gordonia phage Amore2 was isolated from Pittsburgh, Pennsylvania and infects Gordonia terrae 3612. Amore2 was placed into Actinobacteria cluster CS1. Its genome is 73,842 bp with 105 predicted open reading frames and 56.6% GC content. The closest similarity of Amore2 is Gordonia phage Austin, with a 98% nucleotide identity.

Combined Perioperative Lapatinib and Trastuzumab in Early HER2-Positive Breast Cancer Identifies Early Responders: Randomized UK EPHOS-B Trial Long-Term Results.

PURPOSE: EPHOS-B aimed to determine whether perioperative anti-HER2 therapy inhibited proliferation and/or increased apoptosis in HER2-positive breast cancer. PATIENTS AND METHODS: This randomized phase II, two-part, multicenter trial included newly diagnosed women with HER2-positive invasive breast cancer due to undergo surgery. Patients were randomized to: part 1 (1:2:2), no treatment (control), trastuzumab or lapatinib; part 2 (1:1:2) control, trastuzumab, or lapatinib and trastuzumab combination. Treatment was given for 11 days presurgery. Coprimary endpoints were change in Ki67 and apoptosis between baseline and surgery tumor samples (biologic response: ≥30% change). Central pathology review scored residual cancer burden (RCB). Relapse-free survival (RFS) explored long-term effects. RESULTS: Between November 2010 and September 2015, 257 patients were randomized (part 1: control 22, trastuzumab 57, lapatinib 51; part 2: control 29, trastuzumab 32, combination 66). Ki67 response was evaluable for 223 patients: in part 1 Ki67 response occurred in 29/44 (66%) lapatinib versus 18/49 (37%) trastuzumab (P = 0.007) and 1/22 (5%) control (P < 0.0001); in part 2 in 36/49 (74%) combination versus 14/31 (45%) trastuzumab (P = 0.02) and 2/28 (7%) control (P < 0.0001). No significant increase in apoptosis after 11 days was seen in treatment groups. Six patients achieved complete pathologic response (pCR, RCB0) and 13 RCB1, all but two in the combination group. After 6 years median follow-up, 28 (11%) had recurrence and 19 (7%) died. No recurrences or deaths were observed among patients who achieved a pCR. Ki67% falls ≥50% associated with fewer recurrences (P = 0.002). CONCLUSIONS: Early response after short duration anti-HER2 dual therapy identifies cancers dependent on the HER2 pathway providing a strategy for exploring risk-adapted individualized treatment de-escalation.

Safety and efficacy of a home nasogastric monitoring program for premature infants.

BACKGROUND: A novel home monitoring program, in which premature infants are cared for at home with a nasogastric tube in place prior to achievement of full oral feeding, was evaluated. The program combines a digital, fully EMR-integrated, virtual daily rounding platform with direct provider video and telephone contact. METHODS: A case-control study was performed evaluating infants < 34 weeks' gestation who were followed in our program. A historical control group, was created by matching 2 : 1 based on gestational age±6 days, retroactively. RESULT: 15 patients discharged in the program were compared with 30 controls. The home cohort gained an average of 30 g/day compared with the in-hospital group at 27g/day (p = 0.325). The home group required a mean of 5.9±2.9 days to full oral feeding once discharged, not different from the control group at 5.4±3.7 days (p = 0.606). The percentage of oral feeds for the home cohort, however, increased at a rate of 12.2%before discharge compared to rising 57%at home (p < 0.001). The control group spent an additional 8.1±3.9 days in the hospital after reaching criteria. There were no reported adverse events or readmissions. CONCLUSION: Premature infants can safely advance oral feeds using a home monitoring program. While at home, infants gained weight similarly to their inpatient controls, yet gained full oral skills at a significantly faster rate compared to when they were in the hospital.

Study protocol: Minimum effective low dose: anti-human thymocyte globulin (MELD-ATG): phase II, dose ranging, efficacy study of antithymocyte globulin (ATG) within 6 weeks of diagnosis of type 1 diabetes.

INTRODUCTION: Type 1 diabetes (T1D) is a chronic autoimmune disease, characterised by progressive destruction of the insulin-producing ß cells of the pancreas. One immunosuppressive agent that has recently shown promise in the treatment of new-onset T1D subjects aged 12-45 years is antithymocyte globulin (ATG), Thymoglobuline, encouraging further exploration in lower age groups. METHODS AND ANALYSIS: Minimal effective low dose (MELD)-ATG is a phase 2, multicentre, randomised, double-blind, placebo-controlled, multiarm parallel-group trial in participants 5-25 years diagnosed with T1D within 3-9 weeks of planned treatment day 1. A total of 114 participants will be recruited sequentially into seven different cohorts with the first cohort of 30 participants being randomised to placebo, 2.5 mg/kg, 1.5 mg/kg, 0.5 mg/kg and 0.1 mg/kg ATG total dose in a 1:1:1:1:1 allocation ratio. The next six cohorts of 12-15 participants will be randomised to placebo, 2.5 mg/kg, and one or two selected middle ATG total doses in a 1:1:1:1 or 1:1:1 allocation ratio, as dependent on the number of middle doses, given intravenously over two consecutive days. The primary objective will be to determine the changes in stimulated C-peptide response over the first 2 hours of a mixed meal tolerance test at 12 months for 2.5 mg/kg ATG arm vs the placebo. Conditional on finding a significant difference at 2.5 mg/kg, a minimally effective dose will be sought. Secondary objectives include the determination of the effects of a particular ATG treatment dose on (1) stimulated C-peptide, (2) glycated haemoglobin, (3) daily insulin dose, (4) time in range by intermittent continuous glucose monitoring measures, (5) fasting and stimulated dry blood spot (DBS) C-peptide measurements. ETHICS AND DISSEMINATION: MELD-ATG received first regulatory and ethical approvals in Belgium in September 2020 and from the German and UK regulators as of February 2021. The publication policy is set in the INNODIA (An innovative approach towards understanding and arresting Type 1 diabetes consortium) grant agreement (www.innodia.eu). TRIAL REGISTRATION NUMBER: NCT03936634; Pre-results.

Impact of isolation method on cellular activation and presence of specific tendon cell subpopulations during in vitro culture.

Tendon injuries are common and heal poorly, due in part to a lack of understanding of fundamental tendon cell biology. A major impediment to the study of tendon cells is the absence of robust, well-characterized in vitro models. Unlike other tissue systems, current tendon cell models do not account for how differences in isolation methodology may affect the activation state of tendon cells or the presence of various tendon cell subpopulations. The objective of this study was to characterize how common isolation methods affect the behavior, fate, and lineage composition of tendon cell cultures. Tendon cells isolated by explant exhibited reduced proliferative capacity, decreased expression of tendon marker genes, and increased expression of genes associated with fibroblast activation compared to digested cells. Consistently, explanted cells also displayed an increased propensity to differentiate to myofibroblasts compared to digested cells. Explanted cultures from multiple different tendons were substantially enriched for the presence of scleraxis-lineage (Scx-lin+) cells compared to digested cultures, while the overall percentage of S100a4-lineage (S100a4-lin+) cells was dependent on both isolation method and tendon of origin. Neither isolation methods preserved the ratios of Scx-lin+ or S100a4-lin+ to non-lineage cells seen in tendons in vivo. Combined, these data indicate that further refinement of in vitro cultures models is required in order to more accurately understand the effects of various stimuli on tendon cell behavior. Statement of clinical significance: The development of informed in vitro tendon cell models will facilitate enhanced screening of potential therapeutic candidates to improve tendon healing.

The impact of the COVID-19 pandemic on postpartum contraception planning.

OBJECTIVE: The COVID-19 pandemic necessitated rapid adjustment of obstetrical delivery models including fewer antenatal appointments and increased use of telehealth. We hypothesized that an increase in telemedicine and a decrease in antepartum visits owing to the COVID-19 pandemic led to a decreased proportion of people with a postpartum contraception plan at the time of the birth-hospitalization admission and a reduced uptake of top-tier forms of contraception at birth-hospitalization admission and discharge, and the routine postpartum visit, which has otherwise been increasing in recent years.1,2 STUDY DESIGN: A retrospective cohort study comparing a randomly selected sample of people giving birth at a large, tertiary referral center during a regional "shelter in place" order, March 16, 2020, to July 31, 2020, with a previously abstracted random sample of people delivering between November 1, 2017, and April 30, 2018, was conducted. This study was reviewed and approved by the Stanford University Institutional Review Board before its initiation. The study was powered to detect a 10% difference in the proportion of those arriving at birth-hospitalization with a contraceptive plan (power 80%, alpha 0.05). The final sample size included 586 people (318 in the pre-COVID cohort and 268 in the COVID cohort). Multivariable modified Poisson regression model was used to estimate the relative risk of arriving at birth-hospitalization with a contraceptive plan in pre-COVID vs COVID cohorts, adjusting for age, parity, insurance status, and delivery mode. Secondary outcomes included tier of contraception plan at admission, discharge, and 6 weeks postpartum (classified by World Health Organization Tiered-Effectiveness3), attendance at postpartum visit, and whether the postpartum visit was conducted via telehealth. Tiered effectiveness was used for this study's purposes because it was hypothesized that telehealth would mostly affect the provision of top-tier forms of contraception that require in-person initiation. Fisher exact test was used to compare the secondary outcomes. RESULTS: For the 2 cohorts, the median age was 32 years (range, 17-48 years) and median parity was 1 (range, 0-6). The majority (78%) had private insurance and most commonly identified as non-Hispanic White (38%) and Asian (36%). Baseline demographics did not differ between the cohorts. At birth-hospitalization admission, a smaller proportion of people had a postpartum contraceptive plan in the COVID cohort than in the pre-COVID cohort (73.9% vs 99.4%, adjusted risk ratio, 0.87; 95% confidence interval, 0.84-0.91, P<.001). A smaller proportion of people had a plan for top-tier contraception among the COVID cohort compared with the pre-COVID cohort at both admission and discharge (46.0% vs 71.0%, P<.01 and 31.0% vs 37.9%, P=.05) (Figure). More than 80% of the people attended a routine postpartum visit in both cohorts (P=.30) with 17.7% being telehealth visits in the COVID cohort compared with telehealth not being offered pre-COVID. Among those who attended their postpartum visit, the proportion discharged with a plan for interval top-tier contraception that was fulfilled was high in both groups (76.3% pre-COVID vs 71.2% post-COVID, P=.56). CONCLUSION: The study found a significant decrease in people arriving at birth-hospitalization with a contraception plan in the months following a COVID-19 "shelter in place" order when compared with the pre-COVID cohort. It is suspected that changes in the obstetrical service models indirectly deprioritized the most effective forms of postpartum contraception because sterilization requires a signed consent before birth-hospitalization and postplacental intrauterine devices require consent before delivery.4,5 Current state legislation requiring in-person signature to consent for federally funded sterilization remains a barrier. We found that fewer individuals left with top-tier contraception than with plan on admission, especially within the COVID cohort. In addition to clinical contraindications that arise during labor, which preclude placement of an intrauterine device in the postpartum setting, many patients requested an expedited discharge during the peak of the COVID-19 pandemic. As the prenatal care model continues, this transition to adopt virtual visits, reduce visit schedules, and expedite postpartum discharge, actualizing patients' contraceptive plans is increasingly more dependent on early inpatient provision. Maternity care providers should consider initiating postpartum contraception counseling and completing mandatory consents earlier in the antenatal period. This study is inherently limited by its retrospective nature of review and additional qualitative studies may better characterize this trend in contraceptive uptake. In the meantime, obstetrical care providers should carefully evaluate institutional barriers to postpartum contraception during this movement to telehealth.

A Generalizable Multimodal Scrub Training Curriculum in Surgical Sterile Technique.

Introduction: Recent endeavors from governing bodies such as the AAMC have formally recognized the importance of aseptic technique. AAMC guidelines include activities that all graduating physicians should be able to perform with minimum indirect supervision and were developed to recognize these needs. For example, the skills necessary for aseptic technique include daily safety habits and general physician procedures. Methods: We developed a scrub training curriculum and evaluated the program through a quasi-experimental study with a pre- and posttest design. Questions were developed to examine students' perceived knowledge and skills as related to the objectives of the course and to their anxieties, concerns, and future training needs. Results: Between February 2020 and March 2020, 44 students completed the curriculum. Students indicated that self-efficacy significantly increased in all aspects of the curricular goals following curriculum completion. Students identified understanding OR etiquette as the most anxiety-provoking element associated with scrub training. They felt that more time could be spent elucidating this etiquette. On the other hand, tasks such as surgical hand hygiene were the least anxiety-inducing. Discussion: We share this multimodal scrub training curriculum, mapped to the AAMC's guidelines, to reduce variability in teaching strategies and skills acquisition through a standardized curriculum. Also, we effectively imparted these skills and instilled a sense of confidence in learners as they worked to provide their best in patient care and safety.

Executive Functions and Academic Outcomes of Low Birthweight Infants: A Prospective Longitudinal U.S. Cohort.

OBJECTIVE: Executive functions such as working memory and cognitive flexibility are key to lifelong learning. Our hypothesis was that children born low birthweight (LBW), defined as weight < 2,500 g, would have lower cognitive outcomes than those born normal weight, and children with poor executive functioning would be at risk for poor academic outcomes. STUDY DESIGN: We evaluated data from 12,656 children followed prospectively in the Early Childhood Longitudinal Study, Kindergarten Class 2010-2011, assessing outcomes from kindergarten, first grade, and second grade. Multivariable linear and logistic regressions were run evaluating the relationship between birthweight and cognitive outcomes, and the odds of infants with poor executive functioning having poor academic outcomes. RESULTS: Compared with children with normal birthweight, those born LBW had lower mean z-scores for academic and directly assessed executive functions from kindergarten through second grade. LBW children were at an increased risk of scoring in the bottom 20% of children at all time points: second-grade reading odds ratio (OR) = 1.60 (95% confidence interval [CI:] 1.23-2.09), math OR = 1.49 (95% CI: 1.21-1.84), science OR = 1.41 (95% CI: 1.11-1.81), cognitive flexibility OR = 1.61 (95% CI: 1.27-2.02), and working memory OR = 1.40 (95% CI: 1.10-1.77). CONCLUSION: LBW infants remain at risk of poor cognitive outcomes in second grade. Early difficulties with executive functioning can increase the risk of a child's academic performance years later.

Preclinical Surgical Preparatory Course and the NRMP Match: Early Exposure and Surgical Recruitment a 10-Year Follow-Up.

OBJECTIVE: Many medical students mentally commit to specialties prior to entering clerkships. This is why early preclinical interactions with surgical specialties, through mentorship and/or interest groups, increases the opportunity to nurture enthusiasm for surgery. In 2007, a course providing preclinical medical students with introductory surgical skills training and preparation for the surgical environment ("SURG205") was established at our institution. The course underwent a major revision in 2016, increasing intraoperative mentorship by matching students to surgical attendings and requiring students to scrub into operative cases together. We anticipate that the positive surgical experiences created by the course will lead to further development and enhancement of student interest in surgical specialties-interest that we hypothesized would reflect in their National Resident Matching Program (NRMP) Match outcomes. DESIGN: NRMP results from 2010 to 2019 were cross-referenced with a database of students who participated in the SURG205 course from 2007 to 2016. With this, we examined the correlation between student participation in SURG205 and surgical specialty match. Descriptive statistics were used to review the trends of the NRMP results, and Pearson's correlation was used to determine the relationship and its significance. SETTING: This study was conducted in a single private medical school in California. PARTICIPANTS: Specialties considered "surgical" included: General Surgery, integrated programs-such as Plastic, Thoracic, or Vascular surgery, Obstetrics and Gynecology, Orthopedic Surgery, Otolaryngology, Neurosurgery, and Urology. All other specialties were considered nonsurgical. Students identified as having participated in SURG205 and who then also took part in the NRMP. RESULTS: Seven hundred eighty students underwent the Match process from 2010 to 2019. 144 (18.5%) of these students participated in SURG205 between 2007 and 2016. Each Match class ranged in size from 62 to 91 (median = 77.5, IQR = 14.5) students. (Table 1) Two-hundred and nineteen students (28.1%) matched into a surgical specialty, of which 34 (15.5%) selected general surgery. From 2010 to 2019 the rate of students who matched into surgical specialties averaged 28.1% per year with a slight nonstatistically significantly increasing trend over that time period R2 = 0.30 (p = 0.09; Fig. 1). There was a significant increase in trend in proportion of students who took the course and matched into any specialty between 2010 and 2019 (R2 = 0.85, p = 0.0002; Fig. 2). And, there was a statistically significant positive relationship between students taking the course and matching into a surgical specialty (R2 = 0.63, p = 0.01; Fig. 3). CONCLUSION: Our results highlight the increasing tendency of students who pursue surgical specialties having previously participated in this early exposure courses. Not only is student interest created and encouraged through positive mentorship experiences, but that interest may be associated with increases in application rates and eventual match into the specialty. General surgery training programs might consider these trends when designing courses to ease transitions into first-year residency positions-such as fourth-year surgical boot camps, surgical procedure-based anatomy courses, and mentorship frameworks. This information further justifies the cost and time commitment required to administer these programs for students.

Validity Evidence for a Knowledge Assessment Tool for a Mastery Learning Scrub Training Curriculum.

PURPOSE: To examine the validity evidence for a scrub training knowledge assessment tool to demonstrate the utility and robustness of a multimodal, entrustable professional activity (EPA)-aligned, mastery learning scrub training curriculum. METHOD: Validity evidence was collected for the knowledge assessment used in the scrub training curriculum at Stanford University School of Medicine from April 2017 to June 2018. The knowledge assessment had 25 selected response items that mapped to curricular objectives, EPAs, and operating room policies. A mastery passing standard was established using the Mastery Angoff and Patient-Safety approaches. Learners were assessed pre curriculum, post curriculum, and 6 months after the curriculum. RESULTS: From April 2017 to June 2018, 220 medical and physician assistant students participated in the scrub training curriculum. The mean pre- and postcurriculum knowledge scores were 74.4% (standard deviation [SD] = 15.6) and 90.1% (SD = 8.3), respectively, yielding a Cohen's d = 1.10, P < .001. The internal reliability of the assessment was 0.71. Students with previous scrub training performed significantly better on the precurriculum knowledge assessment than those without previous training (81.9% [SD = 12.6] vs 67.0% [SD = 14.9]; P < .001). The mean item difficulty was 0.74, and the mean item discrimination index was 0.35. The Mastery Angoff overall cut score was 92.0%. CONCLUSIONS: This study describes the administration of and provides validity evidence for a knowledge assessment tool for a multimodal, EPA-aligned, mastery-based curriculum for scrub training. The authors support the use of scores derived from this test for assessing scrub training knowledge among medical and physician assistant students.

Detection of visually occult metastatic lymph nodes using molecularly targeted fluorescent imaging during surgical resection of pancreatic cancer.

BACKGROUND: Although most patients with PDAC experience distant failure after resection, a significant portion still present with local recurrence. Intraoperative fluorescent imaging can potentially facilitate the visualization of involved peritumoral LNs and guide the locoregional extent of nodal dissection. Here, the efficacy of targeted intraoperative fluorescent imaging was examined in the detection of metastatic lymph nodes (LNs) during resection of pancreatic ductal adenocarcinoma (PDAC). METHODS: A dose-escalation prospective study was performed to assess feasibility of tumor detection within peripancreatic LNs using cetuximab-IRDye800 in PDAC patients. Fluorescent imaging of dissected LNs was analyzed ex vivo macroscopically and microscopically and fluorescence was correlated with histopathology. RESULTS: A total of 144 LNs (72 in the low-dose and 72 in the high-dose cohort) were evaluated. Detection of metastatic LNs by fluorescence was better in the low-dose (50 mg) cohort, where sensitivity and specificity was 100% and 78% macroscopically, and 91% and 66% microscopically. More importantly, this method was able to detect occult foci of tumor (measuring < 5 mm) with a sensitivity of 88% (15/17 LNs). CONCLUSION: This study provides proof of concept that intraoperative fluorescent imaging with cetuximab-IRDye800 can facilitate the detection of peripancreatic lymph nodes often containing subclinical foci of disease.

Recommendations for reporting on emerging optical imaging agents to promote clinical approval.

Intraoperative fluorescence imaging is particularly well-suited for surgical applications due to its inherently high sensitivity, resolution, and ability to provide images in real-time. To date, the intraoperative observation of fluorescence has largely been subjective. With the need to show objective evidence in order to demonstrate the benefit of this technique, quantitative data needs to be provided to overseeing regulatory bodies. Standardization of fluorescence imaging protocols would improve reproducibility and minimize inter- and intra-institution variance. This would allow studies to be conducted using the same injection techniques, imaging times, reconstruction methods, and analyses. Here, we provide recommendations for standardized methodologies with the goal of setting a minimum requirement for reporting fluorescence-guided surgery results based on both qualitative and (semi-) quantitative data collection. Clinical trials using fluorescence-guided surgery should present results of three critical elements; 1) intra-operative imaging, 2) specimen mapping and pathology correlation, and 3) target validation. Qualitative analyses should consist of a bright field image, black-and-white fluorescence image, pseudo-colored fluorescence overlay image, and/or heat-map whereby fluorescence signal intensity differences are displayed on a color spectrum. Quantitative analyses should include 1) intraoperative data (consisting of images or video, raw numeric values and ratios); 2) specimen mapping, for correlation of fluorescence with the presence of disease (performed using fresh tissue); and 3) target validation (designed to determine fluorescence intensity relative to receptor density of a specific area). Including the aforementioned methods of both qualitative and quantitative analyses will ensure that trial results are comparable and could be collated in future studies to expedite FDA approval.