The First Generation of Asian American Pediatric Surgical Trainees in North America.

INTRODUCTION: Pediatric surgical trainees come from diverse races and ethnicities. However, Asian-Americans (AAs) including West, South, and East Asians may represent a unique group of individuals. We sought to identify any unique challenges and experiences. METHODS: Pediatric surgical trainees were identified from, "The Genealogy of North American Pediatric Surgery: From Ladd to Now" and "Celebrating 50 Years: Canadian Association of Paediatric Surgeons/Association Canadienne de Chirurgie Pediatrique". A database was compiled, and AAs identified who completed their pediatric surgical training on or before 1980. Personal interviews and online sources provided further information. RESULTS: Of 635 pediatric surgical trainees in North America (NA) there were 49 AA trainees (7.7%). There was insufficient information for seven, thus leaving 42 (41 male, one female) for review. The region of Asia of origin included 16 East, 16 West, and 10 South. Thirty-seven (88.0%) had moved to NA for training. The most frequent training programs included seven from Toronto and four each at Buffalo, Detroit, Pittsburgh, and Chicago (Children's Memorial). Thirty-five (83%) trainees spent most of their careers in NA while 7 (17%) practiced in their home country. CONCLUSIONS: The first AA pediatric surgical trainees voiced few examples of discrimination but indicated needs to adjust to the NA culture and often confusion over non-Western names. Mentorship was valued and gratitude expressed over the opportunity offered to train in NA. While some had intended to return to their home countries, plans changed due to meeting spouses or political turmoil. Many of those reviewed sought each other out at national meetings.

Contrast Challenge Algorithms for Adhesive Small Bowel Obstructions Are Safe in Children: A Multi-Institutional Study.

OBJECTIVE: The purpose of this study was to evaluate the safety of a water-soluble contrast challenge as part of a nonoperative management algorithm in children with an adhesive small bowel obstruction (ASBO). BACKGROUND: Predicting which children will successfully resolve their ASBO with non-operative management at the time of admission remains difficult. Additionally, the safety of a water-soluble contrast challenge for children with ASBO has not been established in the literature. METHODS: A retrospective review was performed of patients who underwent non-operative management for an ASBO and received a contrast challenge across 5 children's hospitals between 2012 and 2020. Safety was assessed by comparing the complication rate associated with a contrast challenge against a pre-specified maximum acceptable level of 5%. Sensitivity, specificity, negative (NPV) and positive (PPV) predictive values of a contrast challenge to identify successful nonoperative management were calculated. RESULTS: Of 82 children who received a contrast challenge, 65% were successfully managed nonoperatively. The most common surgical indications were failure of the contrast challenge or failure to progress after initially passing the contrast challenge. There were no complications related to contrast administration (0%; 95% confidence interval: 0-3.6%, P = 0.03). The contrast challenge was highly reliable in determining which patients would require surgery and which could be successfully managed non-operatively (sensitivity 100%, specificity 86%, NPV 100%, PPV 93%). CONCLUSION: A contrast challenge is safe in children with ASBO and has a high predictive value to assist in clinical decision-making.

Reducing Unnecessary Oophorectomies for Benign Ovarian Neoplasms in Pediatric Patients.

Importance: Although most ovarian masses in children and adolescents are benign, many are managed with oophorectomy, which may be unnecessary and can have lifelong negative effects on health. Objective: To evaluate the ability of a consensus-based preoperative risk stratification algorithm to discriminate between benign and malignant ovarian pathology and decrease unnecessary oophorectomies. Design, Setting, and Participants: Pre/post interventional study of a risk stratification algorithm in patients aged 6 to 21 years undergoing surgery for an ovarian mass in an inpatient setting in 11 children's hospitals in the United States between August 2018 and January 2021, with 1-year follow-up. Intervention: Implementation of a consensus-based, preoperative risk stratification algorithm with 6 months of preintervention assessment, 6 months of intervention adoption, and 18 months of intervention. The intervention adoption cohort was excluded from statistical comparisons. Main Outcomes and Measures: Unnecessary oophorectomies, defined as oophorectomy for a benign ovarian neoplasm based on final pathology or mass resolution. Results: A total of 519 patients with a median age of 15.1 (IQR, 13.0-16.8) years were included in 3 phases: 96 in the preintervention phase (median age, 15.4 [IQR, 13.4-17.2] years; 11.5% non-Hispanic Black; 68.8% non-Hispanic White); 105 in the adoption phase; and 318 in the intervention phase (median age, 15.0 [IQR, 12.9-16.6)] years; 13.8% non-Hispanic Black; 53.5% non-Hispanic White). Benign disease was present in 93 (96.9%) in the preintervention cohort and 298 (93.7%) in the intervention cohort. The percentage of unnecessary oophorectomies decreased from 16.1% (15/93) preintervention to 8.4% (25/298) during the intervention (absolute reduction, 7.7% [95% CI, 0.4%-15.9%]; P = .03). Algorithm test performance for identifying benign lesions in the intervention cohort resulted in a sensitivity of 91.6% (95% CI, 88.5%-94.8%), a specificity of 90.0% (95% CI, 76.9%-100%), a positive predictive value of 99.3% (95% CI, 98.3%-100%), and a negative predictive value of 41.9% (95% CI, 27.1%-56.6%). The proportion of misclassification in the intervention phase (malignant disease treated with ovary-sparing surgery) was 0.7%. Algorithm adherence during the intervention phase was 95.0%, with fidelity of 81.8%. Conclusions and Relevance: Unnecessary oophorectomies decreased with use of a preoperative risk stratification algorithm to identify lesions with a high likelihood of benign pathology that are appropriate for ovary-sparing surgery. Adoption of this algorithm might prevent unnecessary oophorectomy during adolescence and its lifelong consequences. Further studies are needed to determine barriers to algorithm adherence.

Disparities in the Management of Pediatric Breast Masses.

INTRODUCTION: Disparities in surgical management have been documented across a range of disease processes. The objective of this study was to investigate sociodemographic disparities in young females undergoing excision of a breast mass. METHODS: A retrospective study of females aged 10-21 y who underwent surgery for a breast lesion across eleven pediatric hospitals from 2011 to 2016 was performed. Differences in patient characteristics, workup, management, and pathology by race/ethnicity, insurance status, median neighborhood income, and urbanicity were evaluated with bivariate and multivariable regression analyses. RESULTS: A total of 454 females were included, with a median age of 16 y interquartile range (IQR: 3). 44% of patients were nonHispanic (NH) Black, 40% were NH White, and 7% were Hispanic. 50% of patients had private insurance, 39% had public insurance, and 9% had other/unknown insurance status. Median neighborhood income was $49,974, and 88% of patients resided in a metropolitan area. NH Whites have 4.5 times the odds of undergoing preoperative fine needle aspiration or core needle biopsy compared to NH Blacks (CI: 2.0, 10.0). No differences in time to surgery from the initial imaging study, size of the lesion, or pathology were observed on multivariable analysis. CONCLUSIONS: We found no significant differences by race/ethnicity, insurance status, household income, or urbanicity in the time to surgery after the initial imaging study. The only significant disparity noted on multivariable analysis was NH White patients were more likely to undergo preoperative biopsy than were NH Black patients; however, the utility of biopsy in pediatric breast masses is not well established.

Management of Pediatric Breast Masses: A Multi-institutional Retrospective Cohort Study.

BACKGROUND: The objective of our study was to describe the workup, management, and outcomes of pediatric patients with breast masses undergoing operative intervention. MATERIALS AND METHODS: A retrospective cohort study was conducted of girls 10-21 y of age who underwent surgery for a breast mass across 11 children's hospitals from 2011 to 2016. Demographic and clinical characteristics were summarized. RESULTS: Four hundred and fifty-three female patients with a median age of 16 y (IQR: 3) underwent surgery for a breast mass during the study period. The most common preoperative imaging was breast ultrasound (95%); 28% reported the Breast Imaging Reporting and Data System (BI-RADS) classification. Preoperative core biopsy was performed in 12%. All patients underwent lumpectomy, most commonly due to mass size (45%) or growth (29%). The median maximum dimension of a mass on preoperative ultrasound was 2.8 cm (IQR: 1.9). Most operations were performed by pediatric surgeons (65%) and breast surgeons (25%). The most frequent pathology was fibroadenoma (75%); 3% were phyllodes. BI-RADS scoring ≥4 on breast ultrasound had a sensitivity of 0% and a negative predictive value of 93% for identifying phyllodes tumors. CONCLUSIONS: Most pediatric breast masses are self-identified and benign. BI-RADS classification based on ultrasound was not consistently assigned and had little clinical utility for identifying phyllodes.

Factors Associated with Torsion in Pediatric Patients with Ovarian Masses.

BACKGROUND: Management of ovarian torsion has evolved toward ovarian preservation regardless of ovarian appearance during surgery. However, patients with torsion and an ovarian neoplasm undergo a disproportionately high rate of oophorectomy. Our objectives were to identify factors associated with ovarian torsion among females with an ovarian mass and to determine if torsion is associated with malignancy. METHODS: A retrospective review of females aged 2-21 y who underwent an operation for an ovarian cyst or neoplasm between 2010 and 2016 at 10 children's hospitals was performed. Multivariate logistic regression was used to assess factors associated with torsion. Imaging data were assessed for sensitivity, specificity, and predictive value in identifying ovarian torsion. RESULTS: Of 814 girls with an ovarian neoplasm, 180 (22%) had torsion. In risk-adjusted analyses, patients with a younger age, mass size >5 cm, abdominal pain, and vomiting had an increased likelihood of torsion (P < 0.01 for all). Patients with a mass >5 cm had two times the odds of torsion (odds ratio: 2.1; confidence interval: 1.2, 3.6). Imaging was not reliable at identifying torsion (sensitivity 34%, positive predictive value 49%) or excluding torsion (specificity 72%, negative predictive value 87%). The rates of malignancy were lower in those with an ovarian mass and torsion than those without torsion (10% versus 17%, P = 0.01). Among the 180 girls with torsion and a mass, 48% underwent oophorectomy of which 14% (n = 12) had a malignancy. CONCLUSIONS: In females with an ovarian neoplasm, torsion is not associated with an increased risk of malignancy and ovarian preservation should be considered.

Inter-rater Reliability of Sacral Ratio Measurements in Patients with Anorectal Malformations.

BACKGROUND: Anorectal malformations (ARMs) are a spectrum of congenital anomalies with varying prognosis for fecal continence. The sacral ratio (SR) is a measure of sacral development that has been proposed as a method to predict future fecal continence in children with ARM. The aim of this study was to quantify the inter-rater reliability (IRR) of SR calculations by radiologists at different institutions. MATERIALS AND METHODS: x-Rays in the anteroposterior (AP) and lateral planes were reviewed by a pediatric radiologist at each of six different institutions. Subsequently, images were reviewed by a single, central radiologist. The IRR was assessed by calculating Pearson correlation coefficients and intraclass correlation coefficients from linear mixed models with patient and rater-level random intercepts. RESULTS: Imaging from 263 patients was included in the study. The mean inter-rater absolute difference in the AP SR was 0.05 (interquartile range, 0.02-0.10), and in the lateral SR was 0.16 (interquartile range, 0.06-0.25). Overall, the IRR was excellent for AP SRs (intraclass correlation coefficient [ICC], 81.5%; 95% confidence interval, 75.1%-86.0%) and poor for lateral SRs (ICC, 44.0%; 95% CI, 29.5%-59.2%). For both AP and lateral SRs, ICCs were similar when examined by the type of radiograph used for calculation, severity of the ARM, presence of sacral or spinal anomalies, and age at imaging. CONCLUSIONS: Across radiologists, the reliability of SR calculations was excellent for the AP plane but poor for the lateral plane. These results suggest that better standardization of lateral SR measurements is needed if they are going to be used to counsel families of children with ARM.

Association of Nonoperative Management Using Antibiotic Therapy vs Laparoscopic Appendectomy With Treatment Success and Disability Days in Children With Uncomplicated Appendicitis.

Importance: Nonoperative management with antibiotics alone has the potential to treat uncomplicated pediatric appendicitis with fewer disability days than surgery. Objective: To determine the success rate of nonoperative management and compare differences in treatment-related disability, satisfaction, health-related quality of life, and complications between nonoperative management and surgery in children with uncomplicated appendicitis. Design, Setting, and Participants: Multi-institutional nonrandomized controlled intervention study of 1068 children aged 7 through 17 years with uncomplicated appendicitis treated at 10 tertiary children's hospitals across 7 US states between May 2015 and October 2018 with 1-year follow-up through October 2019. Of the 1209 eligible patients approached, 1068 enrolled in the study. Interventions: Patient and family selection of nonoperative management with antibiotics alone (nonoperative group, n = 370) or urgent (≤12 hours of admission) laparoscopic appendectomy (surgery group, n = 698). Main Outcomes and Measures: The 2 primary outcomes assessed at 1 year were disability days, defined as the total number of days the child was not able to participate in all of his/her normal activities secondary to appendicitis-related care (expected difference, 5 days), and success rate of nonoperative management, defined as the proportion of patients initially managed nonoperatively who did not undergo appendectomy by 1 year (lowest acceptable success rate, ≥70%). Inverse probability of treatment weighting (IPTW) was used to adjust for differences between treatment groups for all outcome assessments. Results: Among 1068 patients who were enrolled (median age, 12.4 years; 38% girls), 370 (35%) chose nonoperative management and 698 (65%) chose surgery. A total of 806 (75%) had complete follow-up: 284 (77%) in the nonoperative group; 522 (75%) in the surgery group. Patients in the nonoperative group were more often younger (median age, 12.3 years vs 12.5 years), Black (9.6% vs 4.9%) or other race (14.6% vs 8.7%), had caregivers with a bachelor's degree (29.8% vs 23.5%), and underwent diagnostic ultrasound (79.7% vs 74.5%). After IPTW, the success rate of nonoperative management at 1 year was 67.1% (96% CI, 61.5%-72.31%; P = .86). Nonoperative management was associated with significantly fewer patient disability days at 1 year than did surgery (adjusted mean, 6.6 vs 10.9 days; mean difference, -4.3 days (99% CI, -6.17 to -2.43; P < .001). Of 16 other prespecified secondary end points, 10 showed no significant difference. Conclusion and Relevance: Among children with uncomplicated appendicitis, an initial nonoperative management strategy with antibiotics alone had a success rate of 67.1% and, compared with urgent surgery, was associated with statistically significantly fewer disability days at 1 year. However, there was substantial loss to follow-up, the comparison with the prespecified threshold for an acceptable success rate of nonoperative management was not statistically significant, and the hypothesized difference in disability days was not met. Trial Registration: ClinicalTrials.gov Identifier: NCT02271932.

The impact of psychiatric comorbidities on patient-reported surgical outcomes in adults treated for the median arcuate ligament syndrome.

OBJECTIVE: Median arcuate ligament syndrome (MALS) is an often overlooked, surgically correctable condition that mimics functional chronic abdominal pain. Patient-reported surgical outcomes are unpredictable in MALS. The objective of this study was to define the psychiatric comorbidities in a cohort of adults undergoing surgery for MALS and to determine whether these comorbidities are predictive of patient-reported quality of life (QOL) outcomes. METHODS: A prospective observational trial was conducted between April 1, 2010, and December 31, 2015, at a single tertiary care hospital. Adults with a diagnosis of chronic abdominal pain in the setting of celiac artery compression were enrolled in a prospective Institutional Review Board-approved observational trial. Patients completed psychological assessments before surgery for MALS and at 6 months after surgery. The primary outcome was patient-reported health-related QOL (young adult version of the Pediatric Quality of Life Inventory). RESULTS: A total of 51 patients (80% female; n = 41) with a mean age of 30.5 (±12.4) years were enrolled. Surgery significantly improved celiac artery hemodynamics in the entire cohort (P < .0001) as well as overall QOL (67.8 ± 14.6 [before surgery] vs 80.3 ± 13.7 [after surgery]; P < .001). Psychiatric diagnoses were common in this cohort, with 14 of 51 (28%) patients meeting criteria for a psychiatric diagnosis. There were no differences in the number of patients with psychiatric diagnoses between presurgical and postsurgical evaluations (14 [28%] vs 13 [26%]; P = .8). Exploratory analyses suggest that having a psychiatric diagnosis at the presurgical evaluation may predict significantly lower postsurgical QOL (R2 = 0.009; P = .01). CONCLUSIONS: Surgery improves patient-reported QOL in adults treated for MALS. Psychiatric diagnoses are common in adults with MALS and predict worse patient-reported QOL outcomes.

Psychological Factors and Outcomes in the Surgical Treatment of Pediatric Patients With Median Arcuate Ligament Syndrome.

OBJECTIVE: Median arcuate ligament syndrome (MALS) is a frequently overlooked cause of chronic abdominal pain (CAP), and results in many symptoms that mimic other gastrointestinal conditions that result in CAP. A small, but growing body of literature indicates that surgery improves quality of life (QOL) in patients with MALS. The purpose of the current study was to examine the psychological characteristics of pediatric patients with MALS to determine their prevalence and impact on surgical outcomes. METHODS: Thirty-two pediatric patients completed psychological assessments before surgery, and 6 months postsurgical intervention. Descriptive analyses and t tests were conducted to characterize the sample and compare psychosocial and QOL items. To explore possible associations between coping and ultimate changes in QOL, exploratory multiple regressions were conducted. RESULTS: Comorbid psychological conditions were common, occurring in about half the sample before and after surgery. Current pain significantly improved, as well as patient and parent-reported QOL constructs (Ps < 0.05). Parent-reported observations of patients using catastrophizing or helpless strategies to cope with pain before surgery was significantly associated with changes in patient and parent-reported QOL following surgery (Ps = 0.04). CONCLUSIONS: Comorbid psychological conditions are common in pediatric patients with MALS, and are maintained following surgery. While surgery improved pain and QOL, the need for presurgical psychological interventions for MALS is implicated.

Characterisation of CCT271850, a selective, oral and potent MPS1 inhibitor, used to directly measure in vivo MPS1 inhibition vs therapeutic efficacy.

BACKGROUND: The main role of the cell cycle is to enable error-free DNA replication, chromosome segregation and cytokinesis. One of the best characterised checkpoint pathways is the spindle assembly checkpoint, which prevents anaphase onset until the appropriate attachment and tension across kinetochores is achieved. MPS1 kinase activity is essential for the activation of the spindle assembly checkpoint and has been shown to be deregulated in human tumours with chromosomal instability and aneuploidy. Therefore, MPS1 inhibition represents an attractive strategy to target cancers. METHODS: To evaluate CCT271850 cellular potency, two specific antibodies that recognise the activation sites of MPS1 were used and its antiproliferative activity was determined in 91 human cancer cell lines. DLD1 cells with induced GFP-MPS1 and HCT116 cells were used in in vivo studies to directly measure MPS1 inhibition and efficacy of CCT271850 treatment. RESULTS: CCT271850 selectively and potently inhibits MPS1 kinase activity in biochemical and cellular assays and in in vivo models. Mechanistically, tumour cells treated with CCT271850 acquire aberrant numbers of chromosomes and the majority of cells divide their chromosomes without proper alignment because of abrogation of the mitotic checkpoint, leading to cell death. We demonstrated a moderate level of efficacy of CCT271850 as a single agent in a human colorectal carcinoma xenograft model. CONCLUSIONS: CCT271850 is a potent, selective and orally bioavailable MPS1 kinase inhibitor. On the basis of in vivo pharmacodynamic vs efficacy relationships, we predict that more than 80% inhibition of MPS1 activity for at least 24 h is required to achieve tumour stasis or regression by CCT271850.

Diagnostic Performance of Magnetic Resonance Imaging for Pediatric Ovarian Neoplasms: A Multi-Institutional Review.

STUDY OBJECTIVE: To assess the diagnostic performance of MRI to predict ovarian malignancy alone and compared with other diagnostic studies. METHODS: A retrospective analysis was conducted of patients aged 2-21 years who underwent ovarian mass resection between 2009 and 2021 at 11 pediatric hospitals. Sociodemographic information, clinical and imaging findings, tumor markers, and operative and pathology details were collected. Diagnostic performance for detecting malignancy was assessed by calculating sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for MRI with other diagnostic modalities. RESULTS: One thousand and fifty-three patients, with a median age of 14.6 years, underwent resection of an ovarian mass; 10% (110/1053) had malignant disease on pathology, and 13% (136/1053) underwent preoperative MRI. MRI sensitivity, specificity, PPV, and NPV were 60%, 94%, 60%, and 94%. Ultrasound sensitivity, specificity, PPV, and NPV were 31%, 99%, 73%, and 95%. Tumor marker sensitivity, specificity, PPV, and NPV were 90%, 46%, 22%, and 96%. MRI and ultrasound concordance was 88%, with sensitivity, specificity, PPV, and NPV of 33%, 99%, 75%, and 94%. MRI sensitivity in ultrasound-discordant cases was 100%. MRI and tumor marker concordance was 88% with sensitivity, specificity, PPV, and NPV of 100%, 86%, 64%, and 100%. MRI specificity in tumor marker-discordant cases was 100%. CONCLUSION: Diagnostic modalities used to assess ovarian neoplasms in pediatric patients typically agree. In cases of disagreement, MRI is more sensitive for malignancy than ultrasound and more specific than tumor markers. Selective use of MRI with preoperative ultrasound and tumor markers may be beneficial when the risk of malignancy is uncertain. CONCISE ABSTRACT: This retrospective review of 1053 patients aged 2-21 years who underwent ovarian mass resection between 2009 and 2021 at 11 pediatric hospitals found that ultrasound, tumor markers, and MRI tend to agree on benign vs malignant, but in cases of disagreement, MRI is more sensitive for malignancy than ultrasound.

Median arcuate ligament syndrome: a cost analysis to determine the economic burden of a rarely diagnosed disease.

Background: Chronic abdominal pain (CAP) is a medical condition resulting in enormous economic burden and healthcare utilization costs. One understudied source of CAP is the median arcuate ligament syndrome (MALS). MALS is often not diagnosed and treated for a variety of reasons, including the fact that MALS is highly comorbid with psychological symptoms and psychiatric disorders similar to CAP. To better inform future work on the study of MALS, we undertook a pilot study to estimate the economic impact and public health burden of this condition. We hypothesized that MALS imposes a significant public health burden. Methods: Pediatric and adult patients enrolled in a prospective study undergoing multidisciplinary evaluation and treatment for MALS at a tertiary care facility were invited to participate in a brief self-report survey, the Direct and Indirect Medical Care Impact of MALS Form, to capture health care resources including procedures, surgeries, health care visits, and absenteeism (school and work). To estimate costs from the Direct and Indirect Medical Care Impact of MALS Form, the medical care usage data self-reported by patients were converted to dollar value utilizing FSC-93 billing data and corresponding current procedural terminology (CPT) codes for procedures and provider visits one year prior to surgery and then following surgery. Descriptive analyses were conducted to characterize the sample in terms of demographics and reported absences from school and work. Results: One hundred and nineteen patients (mean age = 30.9 ± 13.0) completed the questionnaires, yielding a 57% response rate. 82.4% (n = 98) of the participants were female and 90.8% (n = 108) were non-Hispanic/Latine white. The mean and median surgical follow-up periods were 5.3 and 5.4 years, respectively. Overall, median cost of provider and ancillary healthcare provider visits for each patient was (US)$19,119 including the pre-operative and post-operative visits. The mean cost for providers alone was (US)$28,908. Wilcoxon signed-ranks tests indicated that the postoperative missed number of days of school were significantly lower than the pre-surgical number of missed school days (Z = -3.36, p = 0.001). Similarly, there were significantly less missed work-days following surgery than before for the entire sample (Z = -2.86, p = 0.004). Conclusion: Median arcuate ligament syndrome imposes a large economic burden on patients and the healthcare system. The current findings, although reflective of a homogenous population, are adding to a growing body of literature suggesting that healthcare disparities play a role in the low rates of diagnosis and treatment of MALS.

Discovery of 2-(3-Benzamidopropanamido)thiazole-5-carboxylate Inhibitors of the Kinesin HSET (KIFC1) and the Development of Cellular Target Engagement Probes.

The existence of multiple centrosomes in some cancer cells can lead to cell death through the formation of multipolar mitotic spindles and consequent aberrant cell division. Many cancer cells rely on HSET (KIFC1) to cluster the extra centrosomes into two groups to mimic the bipolar spindle formation of non-centrosome-amplified cells and ensure their survival. Here, we report the discovery of a novel 2-(3-benzamidopropanamido)thiazole-5-carboxylate with micromolar in vitro inhibition of HSET (KIFC1) through high-throughput screening and its progression to ATP-competitive compounds with nanomolar biochemical potency and high selectivity against the opposing mitotic kinesin Eg5. Induction of the multipolar phenotype was shown in centrosome-amplified human cancer cells treated with these inhibitors. In addition, a suitable linker position was identified to allow the synthesis of both fluorescent- and trans-cyclooctene (TCO)-tagged probes, which demonstrated direct compound binding to the HSET protein and confirmed target engagement in cells, through a click-chemistry approach.

Natural history and consequence of patent processus vaginalis: An interim analysis from a multi-institutional prospective observational study.

BACKGROUND: The prevalence and natural history of patent processus vaginalis (PPV) are unknown. An interim analysis was performed of a multi-institutional, prospective, observational study in neonates undergoing laparoscopic pyloromyotomy during which bilateral inguinal canals were evaluated. METHODS: Infants under 4 months undergoing laparoscopic pyloromyotomy were enrolled at 8 children's hospitals. The presence of a PPV was evaluated and measurements recorded. Patients with a PPV are undergoing annual phone follow-up to 18 years of age. Interim analysis was performed. RESULTS: In a cohort of 610 patient, 80 did not have a PPV examined, 4 had consent issues and were excluded, leaving 526 patients. Of these, 433 (82%) were male, median age 1.2 months (IQR 0.9, 1.6), median weight 3.89 kg (IQR 3.4, 4.46), and EGA 39 weeks (IQR 37, 40). There were 283 PPVs, 132 bilateral (47%), 116 right (41%), and 35 left (12%). Patients with a PPV were significantly younger (1.1 months (IQR 0.9, 1.5) vs 1.3 months (IQR 0.9, 1.7), p=0.02), weighed less (3.76kg (IQR 3.35, 4.26) vs 3.9kg (IQR 3.4, 4.5) p=0.03) and had a significantly lower EGA at birth (38 weeks (IQR 37, 40) vs 39 weeks (IQR 38, 40) p=0.003). Of 246 eligible infants, 208 (85%) responded to at least one annual follow-up. Two patients had an inguinal hernia repair for a symptomatic hernia, 49- and 51-days post pyloromyotomy. One had an orchiopexy and incidental inguinal hernia repair 120 days post pyloromyotomy; for a total of 3 (1.2%) hernia repairs. No additional hernias were identified in 116 patients with the PPV patients who have been followed for > 1 year. CONCLUSIONS: The presence of a PPV at the time of pyloromyotomy is common but the need for hernia repair is rare within the first year of life. Continued long-term longitudinal follow-up of this cohort is needed. LEVEL OF EVIDENCE: II.

The First Two Years of the Association of Pediatric Surgery Training Program Directors (APSTPD) Transition to Fellowship Course: Lessons Learned and Future Directions.

OBJECTIVE: The first transition to fellowship course for incoming pediatric surgery fellows was held in the US in 2018 and the second in 2019. The course aimed to facilitate a successful transition in to fellowship by introduction of the professional, patient care, and technical aspects unique to pediatric surgery training. The purpose of this study was to evaluate the feasibility and effectiveness of the first two years of this course in the US and discuss subsequent evolution of this endeavor. DESIGN: This is a descriptive and qualitative analysis of two years' experience with the Association of Pediatric Surgery Training Program Directors' (APSTPD) Transition to Fellowship course. Course development and curriculum, including clinical knowledge, soft skills, and hands-on skills labs, are presented. Participating incoming fellows completed multiple choice, boards-style pre- and post-tests. Scores were compared to determine if knowledge was effectively transferred. Participants also completed post-course evaluations and subsequent 3- or 12-month surveys inquiring on the lasting impact of the course on their transition into fellowship. Standard univariate statistics were used to present results. SETTING: The first APSTPD Transition to Fellowship course was held at the Johns Hopkins Hospital in Baltimore, Maryland in 2018, and the second course was held at the Oregon Health and Science University in Portland, Oregon in 2019. PARTICIPANTS: All fellows entering ACGME-certified Pediatric Surgery fellowships in the United States were invited to participate. Twenty fellows accepted and attended in 2018, and fourteen fellows participated in 2019. RESULTS: There were 34 incoming pediatric surgery fellow participants over 2 years. Faculty represented more than 10 institutions each year. Pre- and post-test scores were similar between years, with a significant improvement of scores after completion of the course (67±10% vs 79±8%, p < 0.001). Feedback from participants was overwhelmingly positive, with skills labs being attendees' favorite component. When asked about usefulness of individual course sessions, more attendees found clinical sessions more useful than soft skills (93% vs 73%, p = 0.011). Almost all (90%) of participants reported the course met its stated purpose and would recommend the course to future fellows. This was further reflected on 3 and 12 month follow up surveys wherein 85% stated they found the course helpful during the first few months of fellowship and 90% would still recommend it. CONCLUSIONS: A transition to fellowship course in the US for incoming pediatric surgery fellows is logistically feasible, effective in transfer of knowledge, and highly regarded among attendees. Feedback from each course has been used to improve the subsequent courses, ensuring that it remains a valuable addition to pediatric surgical training in the US.