SUMMARY Clonal evolution and intratumoral heterogeneity drive cancer progression through unknown molecular mechanisms. To address this issue, functional differences between single T-cell acute lymphoblastic leukemia (T-ALL) clones were assessed using a zebrafish transgenic model. Functional variation was observed within individual clones, with a minority of clones enhancing growth rate and leukemia propagating potential with time. Akt pathway activation was acquired in a subset of these evolved clones, which increased the number of leukemia propagating cells through activating mTORC1, elevated growth rate likely by stabilizing the Myc protein, and rendered cells resistant to dexamethasone, which was reversed by combined treatment with an Akt inhibitor. Thus, T-ALL clones spontaneously and continuously evolve to drive leukemia progression even in the absence of therapy-induced selection.

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Protein sequences are expected not to be random but selected in order to form a stable native structure that is kinetically accessible. Therefore our model contains a selective temperature in sequence space (see [S. Ramanathan and E. Shakhnovich, Phys. Rev. E 50, 1303 (1994)] ) to optimize the sequence for the target conformation statistically. Replica calculations, which go beyond quadratic approximations in the field-theoretical Hamiltonian, are presented. A phase diagram indicating the temperatures and selective temperatures at which transitions to a frozen globule, i.e., the native state, occur is obtained. It is shown that going beyond the quadratic approximation in the field Hamiltonian is very important, since it results in a significant change of the phase diagram. Moreover, we suggest that a one-step replica permutation symmetry scheme is sufficient to solve the model. In addition to this we present a result for the sequence correlation function along the chain in the case of a short-ranged potential between the monomers. A correlation function between monomers that form a contact in the native state is given depending on the temperature and the interaction parameter.

BACKGROUND: Although pediatric health care use declined during the coronavirus disease 2019 (COVID-19) pandemic, the impact on children with complex chronic conditions (CCCs) has not been well reported. OBJECTIVE: To describe the impact of the pandemic on inpatient use and outcomes for children with CCCs. METHODS: This multicenter cross-sectional study used data from the Pediatric Health Information System. We examined trends in admissions between January 2020 through March 2021, comparing them to the same timeframe in the previous 3 years (pre-COVID-19). We used generalized linear mixed models to examine the association of the COVID-19 period and outcomes for children with CCCs presenting between March 16, 2020 to March 15, 2021 (COVID-19 period) to the same timeframe in the previous 3 years (pre-COVID-19). RESULTS: Children with CCCs experienced a 19.5% overall decline in admissions during the COVID-19 pandemic. Declines began in the second week of March of 2020, reaching a nadir in early April 2020. Changes in admissions varied over time and by admission indication. Children with CCCs hospitalized for pneumonia and bronchiolitis experienced overall declines in admissions of 49.7% to 57.7%, whereas children with CCCs hospitalized for diabetes experienced overall increases in admissions of 21.2%. Total and index length of stay, costs, and ICU use, although statistically higher during the COVID-19 period, were similar overall to the pre-COVID-19 period. CONCLUSIONS: Total admissions for children with CCCs declined nearly 20% during the pandemic. Among prevalent conditions, the greatest declines were observed for children with CCCs hospitalized with respiratory illnesses. Despite declines in admissions, overall hospital-level outcomes remained similar.

Objective Digital voice assistant technology provides unique opportunities to enhance clinical practice. We aimed to understand factors influencing pediatric providers' current and potential use of this technology in clinical practice. Methods We surveyed pediatric providers regarding current use and interest in voice technology in the workplace. Regression analyses evaluated provider characteristics associated with voice technology use. Among respondents not interested in voice technology, we elicited individual concerns. Results Among 114 respondents, 19 (16.7%) indicated current use of voice technology in clinical practice, and 51 (44.7%) indicated use of voice technology for nonclinical purposes. Fifty-four (47.4%) reported willingness to try digital voice assistant technology in the clinical setting. Providers who had longer clinic visits (odds ratio [OR], 3.11, 95% confidence interval [CI], 1.04, 9.33, p = 0.04), fewer patient encounters per day (p = 0.02), and worked in hospital-based practices (OR, 2.95, 95% CI, 1.08, 8.07, p = 0.03) were more likely to currently use voice technology in the office. Younger providers (p = 0.02) and those confident in the accuracy of voice technology (OR, 3.05, 95% CI, 1.38, 6.74, p = 0.005) were more willing to trial digital voice assistants in the clinical setting. Among respondents unwilling or unsure about trying voice assistant technology, the most common reasons elicited were concerns related to its accuracy (35%), efficiency (33%), and privacy (28%). Conclusion This national survey evaluating use and attitudes toward digital voice assistant technology by pediatric providers found that while only one-eighth of pediatric providers currently use digital voice assistant technology in the clinical setting, almost half are interested in trying it in the future. Younger provider age and confidence in the accuracy of voice technology are associated with provider interest in using voice technology in the clinical setting. Future development of voice technology for clinical use will need to consider accuracy of information, efficiency of use, and patient privacy for successful integration into the workplace.

OBJECTIVES The demands of residency training may impact trainees’ decision to have children. We examined characteristics of pediatric residents’ decisions regarding childbearing, determinants of resident parental leave, and associations with well-being. METHODS A survey of 845 pediatric residents at 13 programs was conducted between October 2019 and May 2020. Survey items included demographics, desire for future children, and logistics of parental leave. Outcomes included parental leave length, burnout and depression screening results, satisfaction with duration of breastfeeding, and satisfaction with parental leave and parenthood decisions. RESULTS Seventy-six percent (639 of 845) of residents responded to the survey. Fifty-two percent (330) of respondents reported delaying having children during residency, and 29% (97) of those were dissatisfied with their decision to do so. Busy work schedule (89.7%), finances (50.9%), and a desire not to extend residency (41.2%) were the most common reasons for delay. Of respondents, 16% were parents and 4% were pregnant or had pregnant partners. Sixty-one parental leaves were reported, and 67% of parents reported dissatisfaction with leave length. The most frequently self-reported determinant of leave duration was the desire not to extend residency training (74%). Program mean leave length was negatively associated with burnout, measured as a dichotomous outcome (odds ratio = 0.81 [95% confidence interval 0.68–0.98]; P = .02). CONCLUSIONS Many pediatric trainees delay parenthood during residency and are not satisfied with their decision to do so. Pediatric resident parental leave remains short and variable in duration, despite the positive association between longer leaves and overall well-being.

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Background Penicillin allergy is the most commonly reported drug allergy, affecting approximately 10% of patients. Although historically there has been concern about administering cephalosporins to patients allergic to penicillin, the rates of cross-reactivity are only approximately 2%. As cephalosporins are the first-line and safest treatment for many infections, unnecessary avoidance of cephalosporins places patients at risk of poor disease outcomes and antibiotic-associated harms. We assessed the relationship between penicillin allergy label and antibiotic selection in pediatric patients with acute osteomyelitis. Methods We performed a retrospective review of inpatients at our quaternary children’s hospital diagnosed with osteomyelitis between 2011 and 2021. During this period, the institutional osteomyelitis clinical pathway recommended clindamycin for patients with cephalosporin but not penicillin allergy. We compared rates of antibiotics used as definitive therapy between patients with and without documented penicillin allergy. Results Of 365 patients hospitalized with a diagnosis of osteomyelitis, 41 (11.2%) had a documented penicillin allergy. First-generation cephalosporins were administered less frequently to penicillin-allergic patients compared with those without documented penicillin allergy (37% vs. 58%, p=.009), while clindamycin was administered more frequently (22% vs. 10%, p=.02). There was no significant difference in vancomycin use (2% vs. 9%, p=.17). Conclusion Patients with osteomyelitis and a penicillin allergy label were significantly less likely to receive a first-generation cephalosporin and significantly more likely to receive clindamycin. Given higher regional resistance rates and more frequent adverse effects, including Clostridioides difficile infection, of clindamycin relative to first-generation cephalosporins, these data support the need for quality improvement work to increase cephalosporin use in patients with penicillin allergy labels. Disclosures Mari M. Nakamura, MD, MPH, Gilead: Grant/Research Support.