Allopurinol use leading to xanthine nephrolithiasis in pediatric tumor lysis syndrome: a case series.

Tumor lysis syndrome (TLS) is a life-threatening metabolic disorder caused by massive tumor lysis. Allopurinol, a xanthine oxidase inhibitor, is initiated during chemotherapy to prevent hyperuricemia and subsequent acute kidney injury (AKI). We report two cases of xanthine nephrolithiasis during TLS in newly diagnosed hematologic malignancy patients receiving prophylactic allopurinol. Allopurinol use likely promoted xanthine crystallization, stone formation, and AKI.

High variability in cardiac education and experiences during United States paediatric critical care fellowships.

BACKGROUND: Paediatric cardiac critical care continues to become more sub-specialised, and many institutions have transitioned to dedicated cardiac ICUs. Literature regarding the effects of these changes on paediatric critical care medicine fellowship training is limited. OBJECTIVE: To describe the current landscape of cardiac critical care education during paediatric critical care medicine fellowship in the United States and demonstrate its variability. METHODS: A review of publicly available information in 2021 was completed. A supplemental REDCap survey focusing on cardiac ICU experiences during paediatric critical care medicine fellowships was e-mailed to all United States Accreditation Council of Graduate Medical Education-accredited paediatric critical care medicine fellowship programme coordinators/directors. Results are reported using inferential statistics. RESULTS: Data from 71 paediatric critical care medicine fellowship programme websites and 41 leadership responses were included. Median fellow complement was 8 (interquartile range: 6, 12). The majority (76%, 31/41) of programmes had a designated cardiac ICU. Median percentage of paediatric critical care medicine attending physicians with cardiac training was 25% (interquartile range: 0%, 69%). Mandatory cardiac ICU time was 16 weeks (interquartile range: 13, 20) with variability in night coverage and number of other learners present. A minority of programmes (29%, 12/41) mandated other cardiac experiences. Median CHD surgical cases per year were 215 (interquartile range: 132, 338). When considering the number of annual cases per fellow, programmes with higher case volume were not always associated with the highest case number per fellow. CONCLUSIONS: There is a continued trend toward dedicated cardiac ICUs in the United States, with significant variability in cardiac training during paediatric critical care medicine fellowship. As the trend toward dedicated cardiac ICUs continues and practices become more standardised, so should the education.

Decline in Pediatric Shelf Examination Performance During COVID-19.

Background Medical student education has been impacted by the ongoing coronavirus 2019 (COVID-19) pandemic. Medical students were removed from clinical settings, and the censuses in pediatric hospitals decreased. While there have been studies starting to evaluate these effects on medical students training in surgical subspecialties, the literature in pediatrics is limited. Objective This study analyzed third-year medical students' National Board of Medical Examiners (NBME) Clinical Science Pediatrics Shelf Exam scores at the conclusion of their core pediatric clerkship. We compared the exam scores before COVID-19 pandemic to those during the pandemic. We hypothesized that the ongoing COVID-19 pandemic would have a negative impact on NBME shelf exam scores and that shelf exam failure rates would increase. Methods Institutional Review Board approval was obtained prior to initiation of this study. We conducted a retrospective review of medical student pediatric shelf exam scores from June 2017 to December 2020 from one large, single institution. We adjusted scores for block schedule timing and standardized them based on national norms published for the year prior. We compared two groups: those who completed their pediatric clerkship experiences before pandemic (predominantly in-person learning) vs. those who completed it during the pandemic (predominantly virtual learning). Groups were compared using chi-square and analysis-of-variance testing. Results We included 991 medical students, 772 before COVID-19 and 219 during COVID-19. Of these, 19 of 772 (2.5%) students failed the exam prior to COVID-19 compared to 19 of 219 (8.7%) during COVID-19 (p < 0.001). Students who completed their pediatric clerkship during COVID-19 were 3.77 times more likely to fail their end-of-clerkship NBME shelf exam (p < 0.001). Conclusions Students who completed their core pediatric clerkship in a predominantly virtual platform during the COVID-19 pandemic were significantly more likely to fail their end-of-clerkship NBME shelf exam. Increased failure rates may suggest issues with acquisition and retainment of pediatric medical knowledge throughout the clerkship, creating knowledge gaps in the foundation of their pediatric experience. Long-term effects of virtual learning platforms will need to be studied further.

Variation in COVID-19 Diagnosis by Zip Code and Race and Ethnicity in Indiana.

Objectives: To describe variations in coronavirus disease 2019 (COVID-19) diagnosis by zip code race and ethnicity in Indiana. Methods: Cross-sectional evaluation of subjects with SARS-CoV-2 at Indiana University Health. We performed two separate analyses, first evaluating likelihood of COVID-19 diagnosis by race (Caucasian, African American, Asian, or other) and ethnicity (Hispanic vs. non-Hispanic) in the cohort encompassing the entire state of Indiana. Subsequently, patient data was geolocated with zip codes in Marion County and the immediate surrounding counties, and descriptive statistical analyses were used to calculate the number of COVID-19 cases per 10,000 persons for each of these zip codes. Results: Indiana had a total of 3,892 positive COVID-19 cases from January 1 to April 30, 2020. The odds of testing positive for COVID-19 were four-fold higher in African Americans than non-African Americans (OR 4.58, 95% CI 4.25-4.94, P < 0.0001). Increased COVID-19 cases per 10,000 persons were seen in zip codes with higher percentage of African American (median infection rate of 17.4 per 10,000 population in zip codes above median % African American compared to 6.7 per 10,000 population in zip codes below median % African American, with an overall median infection rate 9.9 per 10,000 population, P < 0.0001) or Hispanic residents (median infection rate of 15.9 per 10,000 population in zip codes above median % Hispanic compared to 7.0 per 10,000 population in zip codes below median % Hispanic, overall median infection rate 9.6 per 10,000 population, P < 0.0001). Conclusions: Individuals from zip codes with higher percentages of African American, Hispanic, foreign-born, and/or residents living in poverty are disproportionately affected by COVID-19. Urgent work is needed to understand and address the disproportionate burden of COVID-19 in minority communities and when economic disparities are present.

COVID-19-associated apnea and circumoral cyanosis in a 3-week-old.

BACKGROUND: Data regarding coronavirus disease 2019 (COVID-19) cases and outcomes in infants are sparse compared to older pediatric and adult populations. CASE PRESENTATION: We present a three-week-old full-term male with a history of mild hypoxic ischemic encephalopathy (HIE) who was admitted as an inpatient twice for episodes of apnea and perioral cyanosis. The patient tested positive for COVID-19 and negative for other common respiratory viruses at both admissions. CONCLUSIONS: To our knowledge, this is the first report of apnea and perioral cyanosis associated with COVID-19 in an infant. This case highlights a previously undocumented COVID-19 presentation and suggests that even mildly symptomatic infants warrant viral diagnostic testing in an effort to prevent further spread of the disease.

Chemical interactions between fibrosarcoma cancer cells and sensory neurons contribute to cancer pain.

In an experimental model of cancer pain, the hyperalgesia that occurs with osteolytic tumor growth is associated with the sensitization of nociceptors. We examined functional and molecular changes in small-diameter dorsal root ganglion (DRG) neurons to determine cellular mechanisms underlying this sensitization. The occurrence of a Ca2+ transient in response to either KCl (25 mM) or capsaicin (500 nM) increased in small neurons isolated from murine L3-L6 DRGs ipsilateral to fibrosarcoma cell tumors. The increased responses were associated with increased mRNA levels for the Ca2+ channel subunit alpha2delta1 and TRPV1 receptor. Pretreatment with gabapentin, an inhibitor of the alpha2delta1 subunit, blocked the increased response to KCl in vitro and the mechanical hyperalgesia in tumor-bearing mice in vivo. Similar increases in neuronal responsiveness occurred when DRG neurons from naive mice and fibrosarcoma cells were cocultured for 48 h. The CC chemokine ligand 2 (CCL2) may contribute to the tumor cell-induced sensitization because CCL2 immunoreactivity was present in tumors, high levels of CCL2 peptide were present in microperfusates from tumors, and treatment of DRG neurons in vitro with CCL2 increased the amount of mRNA for the alpha2delta1 subunit. Together, our data provide strong evidence that the chemical mediator CCL2 is released from tumor cells and evokes phenotypic changes in sensory neurons, including increases in voltage-gated Ca2+ channels that likely underlie the mechanical hyperalgesia in the fibrosarcoma cancer model. More broadly, this study provides a novel in vitro model to resolve the cellular and molecular mechanisms by which tumor cells drive functional changes in nociceptors.