Twelve-month observational study of children with cancer in 41 countries during the COVID-19 pandemic

Introduction Childhood cancer is a leading cause of death. It is unclear whether the COVID-19 pandemic has impacted childhood cancer mortality. In this study, we aimed to establish all-cause mortality rates for childhood cancers during the COVID-19 pandemic and determine the factors associated with mortality. Methods Prospective cohort study in 109 institutions in 41 countries. Inclusion criteria: children <18 years who were newly diagnosed with or undergoing active treatment for acute lymphoblastic leukaemia, non-Hodgkin's lymphoma, Hodgkin lymphoma, retinoblastoma, Wilms tumour, glioma, osteosarcoma, Ewing sarcoma, rhabdomyosarcoma, medulloblastoma and neuroblastoma. Of 2327 cases, 2118 patients were included in the study. The primary outcome measure was all-cause mortality at 30 days, 90 days and 12 months. Results All-cause mortality was 3.4% (n=71/2084) at 30-day follow-up, 5.7% (n=113/1969) at 90-day follow-up and 13.0% (n=206/1581) at 12-month follow-up. The median time from diagnosis to multidisciplinary team (MDT) plan was longest in low-income countries (7 days, IQR 3-11). Multivariable analysis revealed several factors associated with 12-month mortality, including low-income (OR 6.99 (95% CI 2.49 to 19.68); p<0.001), lower middle income (OR 3.32 (95% CI 1.96 to 5.61); p<0.001) and upper middle income (OR 3.49 (95% CI 2.02 to 6.03); p<0.001) country status and chemotherapy (OR 0.55 (95% CI 0.36 to 0.86); p=0.008) and immunotherapy (OR 0.27 (95% CI 0.08 to 0.91); p=0.035) within 30 days from MDT plan. Multivariable analysis revealed laboratory-confirmed SARS-CoV-2 infection (OR 5.33 (95% CI 1.19 to 23.84); p=0.029) was associated with 30-day mortality. Conclusions Children with cancer are more likely to die within 30 days if infected with SARS-CoV-2. However, timely treatment reduced odds of death. This report provides crucial information to balance the benefits of providing anticancer therapy against the risks of SARS-CoV-2 infection in children with cancer

NTRK fusion oncogenes in pediatric papillary thyroid carcinoma in northeast United States

BACKGROUND An increase in thyroid cancers, predominantly papillary thyroid carcinoma (PTC), has been recently reported in children. METHODS The histopathology of 28 consecutive PTCs from the northeast United States was reviewed. None of the patients (ages 6-18 years; 20 females, 8 males) had significant exposure to radiation. Nucleic acid from tumors was tested for genetic abnormalities (n = 27). Negative results were reevaluated by targeted next-generation sequencing. RESULTS Seven of 27 PTCs (26%) had neurotrophic tyrosine kinase receptor (NTRK) fusion oncogenes (NTRK type 3/ets variant 6 [NTRK3/ETV6], n =5; NTRK3/unknown, n = 1; and NTRK type 1/translocated promoter region, nuclear basket protein [NTRK1/TPR], n = 1), including 5 tumors that measured >2 cm and 3 that diffusely involved the entire thyroid or lobe. All 7 tumors had lymphatic invasion, and 5 had vascular invasion. Six of 27 PTCs (22%) had ret proto-oncogene (RET) fusions (RET/PTC1, n = 5; RET/PTC3, n = 1); 2 tumors measured >2 cm and diffusely involved the thyroid, and 5 had lymphatic invasion, with vascular invasion in 2. Thirteen PTCs had the B-Raf proto-oncogene, serine/threonine kinase (BRAF) valine-to-glutamic acid mutation at position 600 (BRAFV600E) (13 of 27 tumors; 48%), 11 measured <2 cm, and 6 had lymphatic invasion (46%), with vascular invasion in 3. Fusion oncogene tumors, compared with BRAFV600E PTCs, were associated with large size (mean, 2.2 cm vs 1.5 cm, respectively; P =.05), solid and diffuse variants (11 of 13 vs 0 of 13 tumors, respectively; P <.001), and lymphovascular invasion (12 of 13 vs 6 of 13 tumors, respectively; P =.02); BRAFV600E PTCs were predominantly the classic variant (12 of 13 vs 1 of 13 tumors). Two tumors metastasized to the lung, and both had fusion oncogenes (NTRK1/TPR, n = 1; RET/PTC1, n = 1). CONCLUSIONS Fusion oncogene PTC presents with more extensive disease and aggressive pathology than BRAFV600E PTC in the pediatric population. The high prevalence of the NTRK1/NTRK3 fusion oncogene PTCs in the United States is unusual and needs further investigation. Cancer 2016;122:1097-1107

Counseling for opioids prescribed at discharge of hospitalized adolescent trauma patients

Abstract Background Expert consensus recommends prescription opioid safety counseling be provided when prescribing an opioid. This may be especially important for youth with preexistent alcohol and other drug (AOD) use who are at higher risk of developing opioid use disorder. This study examined the frequency that adolescent trauma patients prescribed opioids at hospital discharge received counseling and if this differed by adolescents’ AOD use. Method This study was embedded within a larger prospective stepped-wedge type III hybrid implementation study of AOD screening across a national cohort of pediatric trauma centers. Data were collected during 2018–2021 from admitted adolescent trauma patients (12–17 yo) at seven centers. Patient data were extracted from the electronic health record (EHR) on any prescribed discharged opioids, documentation of counseling delivered on prescribed opioid, who delivered counseling, and patients’ AOD screening results. Additionally, adolescents received an online survey within 30 days of hospital discharge that included asking about hospital discussions on safe use of prescription pain medication. Results Of the 247 adolescent trauma patients enrolled, 158 completed the 30-day survey. AOD screening results were documented in the EHR for 139 patients (88%), with 69 (44.1%) screening AOD-positive. Opioids at discharge were prescribed to 86 (54.4%) adolescent patients, with no significant difference between those screened AOD-positive and AOD-negative (42.4% vs. 46.3%, p = 0.89). Counseling was documented in the EHR for 30 (34.9%) of those prescribed an opioid and was not significantly different by sex, age, race, ethnicity or between adolescent patients with documentation of AOD use (29.3%) versus those who did not (33.3%, p = 0.71). According to the adolescent survey, among those prescribed an opioid, 61.2% reported someone had talked with them about safe use of newly prescribed pain medications with again no difference between AOD-positive and AOD-negative screening results (p = 0.34). Conclusions Although adolescent trauma patients recalled discussions on safe use of prescribed pain medication more often than was documented in the EHR, these discussions were not universal and did not differ if adolescents had screened positive or negative for AOD use as documented in the EHR. Trial Registry: clinicaltrials.gov NCT03297060

Fatores preditivos de complicações graves em cirurgia neonatal

OBJETIVO: investigar a incidência e gravidade das complicações pós-operatórias precoces e identificar fatores de risco para o seu desenvolvimento em recém-nascidos submetidos ao tratamento cirúrgico, sob anestesia geral. MÉTODOS: análise retrospectiva dos dados de 437 neonatos com doença crítica submetidos à cirurgia neonatal num centro cirúrgico pediátrico terciário, entre janeiro de 2000 e dezembro de 2010. A gravidade das complicações ocorridas nos primeiros 30 dias de pós-operatório foi classificada utilizando o sistema de Clavien-Dindo para complicações cirúrgicas, sendo considerados graves os graus III a V. Por análise estatística uni e multivariada avaliaram-se variáveis pré e intraoperatórias com potencial preditivo de complicações pós-operatórias graves. RESULTADOS: a incidência de, pelo menos, uma complicação grave foi 23%, com uma mediana de uma complicação por paciente 1:3. Ao todo, ocorreram 121 complicações graves. Destas, 86 necessitaram de intervenção cirúrgica, endoscópica ou radiológica (grau III), 25 puseram em risco a vida, com disfunção uni ou multi-órgão (grau IV) e dez resultaram na morte do paciente (grau V). As principais complicações foram técnicas (25%), gastrointestinais (22%) e respiratórias (21%). Foram identificados quatro fatores de risco independentes para complicações pós-operatórias graves: reoperação, operação por hérnia diafragmática congênita, prematuridade menor que 32 semanas de idade gestacional e cirurgia abdominal. CONCLUSÃO: a incidência de complicações pós-operatórias graves após cirurgias neonatais, sob anestesia geral, permaneceu elevada. As condições consideradas fatores de risco independentes para complicações graves após a cirurgia neonatal podem ajudar a definir o prognóstico pós-operatório em neonatos com doença cirúrgica e orientar as intervenções para melhoria de resultados