Analysis of fellowship program director opinions of entrustable professional activities in adolescent medicine fellowship.

OBJECTIVES: This study aimed to explore the minimum entrustable professional activity (EPA) supervision levels at which pediatric fellowship program directors (FPDs) would be willing to graduate fellows and the levels deemed necessary for safe and effective practice for each of the common pediatric subspecialty and the four adolescent medicine-specific EPAs. METHODS: This cross-sectional study utilized survey data from pediatric FPDs in 2017. FPDs indicated the minimum level of supervision (LOS) for fellows at graduation and for safe and effective practice. RESULTS: 82 percent (23/28) of adolescent medicine FPDs completed the survey. For each EPA, there were differences (p<0.05) between LOS expected for graduation and for safe and effective practice. There was also variability in the level at which FPDs would graduate fellows. CONCLUSIONS: This study summarizes pediatric FPD opinions regarding the minimum levels of supervision required for fellows at the time of graduation as well as the levels deemed necessary for safe and effective practice. The difference between the minimum LOS at which FPDs would graduate a fellow and that deemed appropriate for safe and effective practice, along with variability in minimum LOS for graduation, highlight the need for clearer standards for fellowship graduation as well as more structured early career support for ongoing learning. These data highlight variability in FPD opinion regarding such expectations and both the need to better define desired training outcomes and potential need for post-graduation supervision in clinical practice.

Differentiating Eosinophilic Esophagitis and Eating/Feeding Disorders.

Eosinophilic esophagitis (EoE) is an inflammatory condition of the esophagus that causes symptoms of esophageal dysmotility. Patients with feeding or eating disorders (ED) can have similar symptoms, and there is a paucity of literature exploring these similarities. Furthermore, EoE can occur in addition to an ED, requiring clinicians to obtain a thorough history, make accurate diagnoses, and adequately treat all underlying conditions. We present 4 pediatric cases highlighting the similarities between EoE and ED symptomatology. Patients 1 to 3 were presumed to have an ED and were subsequently diagnosed with EoE. Patient 4 had a history of previously diagnosed and inadequately treated EoE, but was later found to also have a longstanding ED. The patients presented to the University of Rochester Pediatric Ambulatory Clinics in 2020. This series demonstrates that symptoms of EoE can overlap with those of an ED, such as anorexia nervosa or avoidant restrictive food intake disorder. Therefore, assessment for either EoE or an ED should include questions related to both diagnoses. Symptoms that may raise suspicion of EoE are indigestion, acute (versus chronic) weight loss, and dysphagia, including the inability to swallow pills, particularly in the presence of personal or family history of atopy. Patients with known EoE should be periodically evaluated for the presence of an ED. This case series illustrates that EoE can either present as an ED or complicate the diagnosis and/or treatment of an ED, making prompt diagnosis and treatment essential for successful management of all conditions.

T24 HRAS transformed NIH/3T3 mouse cells (GhrasT-NIH/3T3) in serial tumorigenic in vitro/in vivo passages give rise to increasingly aggressive tumorigenic cell lines T1-A and T2-A and metastatic cell lines T3-HA and T4-PA.

Cancer cells often arise progressively from "normal" to "pre-cancer" to "transformed" to "local metastasis" to "metastatic disease" to "aggressive metastatic disease". Recent whole genome sequencing (WGS) and spectral karyotyping (SKY) of cancer cells and tumorigenic models have shown this progression involves three major types of genome rearrangements: ordered small step-wise changes, more dramatic "punctuated evolution" (chromoplexy), and large catastrophic steps (chromothripsis) which all occur in random combinations to generate near infinite numbers of stochastically rearranged metastatic cancer cell genomes. This paper describes a series of mouse cell lines developed sequentially to mimic this type of progression. This starts with the new GhrasT-NIH/Swiss cell line that was produced from the NIH/3T3 cell line that had been transformed by transfection with HRAS oncogene DNA from the T24 human bladder carcinoma. These GhrasT-NIH/Swiss cells were injected s.c. into NIH/Swiss mice to produce primary tumors from which one was used to establish the T1-A cell line. T1-A cells injected i.v. into the tail vein of a NIH/Swiss mouse produced a local metastatic tumor near the base of the tail from which the T2-A cell line was established. T2-A cells injected i.v. into the tail vein of a nude NIH/Swiss mouse produced metastases in the liver and one lung from which the T3-HA (H=hepatic) and T3-PA (P=pulmonary) cell lines were developed, respectively. T3-HA cells injected i.v. into a nude mouse produced a metastasis in the lung from which the T4-PA cell line was established. PCR analysis indicated the human T24 HRAS oncogene was carried along with each in vitro/in vivo transfer step and found in the T2-A and T4-PA cell lines. Light photomicrographs indicate that all transformed cells are morphologically similar. GhrasT-NIH/Swiss cells injected s.c. produced tumors in 4% of NIH/Swiss mice in 6-10 weeks; T1-A cells injected s.c. produced tumors in 100% of NIH/Swiss mice in 7-10 days. T1-A, T-2A, T3-HA and T4-PA cells when injected i.v. into the tail produced local metastasis in non-nude or nude NIH/Swiss mice. T4-PA cells were more widely metastatic than T3-HA cells when injected i.v. into nude mice. Evaluation of the injected mice indicated a general increase in metastatic potential of each cell line in the progression as compared to the GhrasT-NIH/3T3 transformed cells. A new photomicrographic technique to follow growth rates within six preselected 2×2mm(2) grids per plate is described. Average doubling times of the transformed cells GhrasT-NIH/3T3 (17h), T1A (17.5h), T2A (15.5h), T3-HA (17.5h) and T4-PA (18.5h) (average 17.2h) were significantly faster (P=0.006) than NIH Swiss primary embryonic cells and NIH/3T3 cells (22 h each). This cell series is currently used in this lab for studies of cancer cell inhibitors, mitochondrial biogenesis and gene expression and is available for further study by other investigators for intra- and inter-laboratory comparisons of WGS, transcriptome sequencing, SKY and other analyses. The genome rearrangements in these cells together with their phenotypic properties may help provide more insights into how one tumorigenic progression occurred to produce the various cell lines that led to the highly metastatic T4-PA cell line.