Germline mutations in cancer predisposition genes among pediatric patients with cancer and congenital anomalies.

BACKGROUND: Childhood cancer has a poorly known etiology, and investigating the underlying genetic background may provide novel insights. A recognized association exists between non-chromosomal birth defects and childhood cancer susceptibility. METHODS: We performed whole-exome sequencing and chromosomal microarray analysis in a cohort of childhood cancer (22 individuals, 50% with congenital anomalies) to unravel deleterious germline variants. RESULTS: A diagnostic yield of 14% was found, encompassing heterozygous variants in bona fide dominant Cancer Predisposition Genes (CPGs). Considering candidate and recessive CPGs harboring monoallelic variants, which were also deemed to play a role in the phenotype, the yield escalated to 45%. Most of the deleterious variants were mapped in genes not conventionally linked to the patient's tumor type. Relevant findings were detected in 55% of the syndromic individuals, mostly variants potentially underlying both phenotypes. CONCLUSION: We uncovered a remarkable prevalence of germline deleterious CPG variants, highlighting the significance of a comprehensive genetic analysis in pediatric cancer, especially when coupled with additional clinical signs. Moreover, our findings emphasized the potential for oligogenic inheritance, wherein multiple genes synergistically increase cancer risk. Lastly, our investigation unveiled potentially novel genotype-phenotype associations, such as SETD5 in neuroblastoma, KAT6A in gliomas, JAG1 in hepatoblastomas, and TNFRSF13B in Langerhans cell histiocytosis. IMPACT: Novel gene-phenotype associations and candidate genes for pediatric cancer were unraveled, such as KAT6A in gliomas, SETD5 in neuroblastoma, JAG1 in hepatoblastomas, and TNFRSF13B in Langerhans cell histiocytosis. Our analysis revealed a high frequency of deleterious germline variants, particularly in cases accompanied by additional clinical signs, highlighting the importance of a comprehensive genetic evaluation in childhood cancer. Our findings also underscored the potential for oligogenic inheritance in pediatric cancer risk. Understanding the cancer etiology is crucial for genetic counseling, often influencing therapeutic decisions and offering valuable insights into molecular targets for the development of oncological therapies.

Beyond Clinical Trials: Understanding Neurotrophic Tropomyosin Receptor Kinase Inhibitor Challenges and Efficacy in Real-World Pediatric Oncology.

PURPOSE: Our study aimed to explore real-world treatment scenarios for children and adolescents with neurotrophic tropomyosin receptor kinase (NTRK)-fused tumors, emphasizing access, responses, side effects, and outcomes. PATIENTS AND METHODS: Pooled clinical data from 17 pediatric cases (11 soft-tissue sarcomas, five brain tumors, and one neuroblastoma) treated with larotrectinib and radiologic images for 14 patients were centrally reviewed. Testing for gene fusions was prompted by poor response to treatment, tumor progression, or aggressiveness. RESULTS: Six different NTRK fusion subtypes were detected, and various payment sources for testing and medication were reported. Radiologic review revealed objective tumor responses (OR) in 11 of 14 patients: Complete responses: two; partial responses: nine; and stable disease: three cases. Grades 1 or 2 Common Terminology Criteria for Adverse Events adverse effects were reported in five patients. Regarding the entire cohort's clinical information, 15 of 17 patients remain alive (median observation time: 25 months): four with no evidence of disease and 11 alive with disease (10 without progression). One patient developed resistance to the NTRK inhibitor and died from disease progression while another patient died due to an unrelated cause. CONCLUSION: This real-world study confirms favorable agnostic tumor OR rates to larotrectinib in children with NTRK-fused tumors. Better coordination to facilitate access to medication remains a challenge, particularly in middle-income countries like Brazil.

Acute promyelocytic leukemia in childhood and adolescence: treatment results of a modified AIDA protocol at a Brazilian center.

INTRODUCTION: Acute promyelocytic leukemia currently presents an excellent chance of cure with protocols based on all-trans-retinoic acid (ATRA) and anthracycline or only differentiation agents. However, high early mortality rates continue to be reported METHODS: Between 2000 and 2018, patients were enrolled and retrospectively analyzed by medical records. A modified AIDA protocol, with a 1-year shortening of the treatment duration, reduction in the number of drugs and a strategy to reduce early mortality by the postponement of the initiation of anthracyclines were employed. Overall and event-free survival rates and toxicity were analyzed RESULTS: Thirty-two patients were enrolled, of whom 56% were female, with a median age of 12 years and 34% belonged to the high-risk group. Two patients had the hypogranular variant and three had another cytogenetic alteration, in addition to the t(15;17). The median start of the first anthracycline dose was 7 days. There were two early deaths (6%) due to central nervous system (CNS) bleeding. All patients achieved molecular remission after the consolidation phase. Two children relapsed and were rescued by arsenic trioxide and hematopoietic stem cell transplantation. The presence of disseminated intravascular coagulation (DIC) at diagnosis (p = 0.03) was the only factor with survival impact. The five-year event-free survival (EFS) was 84% and 5-year overall survival (OS) was 90% CONCLUSION: The survival results were comparable to those found in the AIDA protocol, with a low rate of early mortality in relation to the Brazilian reality.

Perceptions of Health Professionals on the Implementation of Integrative and Complementary Practices at a University Pediatric Hospital in Brazil: A Qualitative Interview Study.

BACKGROUND: Despite an increase in use of pediatric complementary and integrative health (PCIH), many healthcare professionals still have an inadequate understanding of such practices and consider their use inappropriate, which might thwart implementation processes. In a qualitative interview study we examined the feedback of conventional healthcare professionals about the integrative practices provided to pediatric patients by an integrative team in a pediatric oncological hospital. METHODS: Fifteen semi-structured interviews were carried out with various conventional healthcare professionals in an university pediatric hospital in São Paulo, Brazil. The interviews were audio-recorded, transcribed and pseudonymized. DSCsoft® and MAXQDA® software assisted in a profound qualitative analysis using the collective subject discourse and thematic analysis method in order to display participants' perspectives on PCIH and the project in their hospital. RESULTS: Interviewees acknowledged their lack of knowledge about PCIH practices and reflected on the limits of their care as well as on new possibilities PCIH could offer. PCIH was perceived by interviewees as an effective supportive tool of care to promote patients' wellbeing, assist overall compliance, strengthen cooperation between professionals, children and their relatives and hence facilitated general patient care. Since PCIH was implemented in their clinic, perceptions led interviewees to wish for increased PCIH offering and a more profound integration of its therapists into the standard of care. DISCUSSION: The coexistence of integrative and conventional practices in the conventional healthcare setting is important to give visibility to the possibilities offered by the integrative pediatrics field. Regular and constant encounters with integrative practices, as well as information access seem crucial to reach a wider openness for PCIH and subsequently a broader application and dissemination of it.

LHX6 promoter hypermethylation in oncological pediatric patients conceived by IVF.

The multifactorial etiology of pediatric cancer is poorly understood. Environmental factors occurring during embryogenesis can disrupt epigenetic signaling, resulting in several diseases after birth, including cancer. Associations between assisted reproductive technologies (ART), such as in vitro fertilization (IVF), and birth defects, imprinting disorders and other perinatal adverse events have been reported. IVF can result in methylation changes in the offspring, and a link with pediatric cancer has been suggested. In this study, we investigated the peripheral blood methylomes of 11 patients conceived by IVF who developed cancer in childhood. Methylation data of patients and paired sex/aged controls were obtained using the Infinium MethylationEPIC Kit (Illumina). We identified 25 differentially methylated regions (DMRs), 17 of them hypermethylated, and 8 hypomethylated in patients. The most significant DMR was a hypermethylated genomic segment located in the promoter region of LHX6, a transcription factor involved in the forebrain development and interneuron migration during embryogenesis. An additional control group was included to verify the LHX6 methylation status in children with similar cancers who were not conceived by ART. The higher LHX6 methylation levels in IVF patients compared to both control groups (healthy children and children conceived naturally who developed similar pediatric cancers), suggested that hypermethylation at the LHX6 promoter could be due to the IVF process and not secondary to the cancer itself. Further studies are required to evaluate this association and the potential role of LHX6 promoter hypermethylation for tumorigenesis.

Novel FERMT3 and PTPRQ Mutations Associated with Leukocyte Adhesion Deficiency-III and Sensorineural Hearing Loss.

Leukocyte adhesion deficiency-III (LAD-III) is a rare genetic disease caused by defective integrin activation in hematopoietic cells due to mutations in the FERMT3 gene. The PTPRQ gene encodes the protein tyrosine phosphatase receptor Q and is essential for the normal maturation and function of hair bundle in the cochlea. Homozygous PTPRQ mutations impair the stereocilia in hair cells which lead to nonsyndromic sensorineural hearing loss (SNHL) with vestibular dysfunction. Here, we report two novel pathogenic homozygous mutations found in two genes, FERMT3 and PTPRQ , in a Brazilian patient with LAD-III and SNHL, which may develop our understanding of the phenotype-genotype correlation and prognosis of patients with these rare diseases.

Major discrepancy between clinical diagnosis of death and anatomopathological findings in adolescents with chronic diseases during 18-years.

OBJECTIVES: To evaluate the inconsistency between clinical diagnosis of death and autopsy findings in adolescents with chronic diseases. METHODS: A cross-sectional study including a sample of adolescents' autopsies who died in a pediatric and adolescent tertiary hospital over 18 consecutive years. During this period, there were n = 2912 deaths, and n = 581/2912(20%) occurred in adolescents. Of these, n = 85/581(15%) underwent autopsies and were analyzed. Further results were divided into two groups: Goldman classes I or II (high disagreement between main clinical diagnosis of death and anatomopathological findings, n = 26) and Goldman classes III, IV or V (low or no disagreement between these two parameters, n = 59). RESULTS: Median age at death (13.5 [10‒19] vs. 13 [10‒19] years, p = 0.495) and disease duration (22 [0‒164] vs. 20 [0‒200] months, p = 0.931), and frequencies for males (58% vs. 44%, p = 0.247) were similar between class I/II vs. class III/IV/V. The frequency of pneumonia (73% vs. 48%, p = 0.029), pulmonary abscess (12% vs. 0%, p = 0.026), as well as isolation of yeast (27% vs. 5%, p = 0.008), and virus (15% vs. 2%, p = 0.029) identified in the autopsy, were significantly higher in adolescents with Goldman class I/II compared to those with Goldman class III/IV/V. In contrast, cerebral edema was significantly lower in adolescents of the first group (4% vs. 25%, p = 0.018). CONCLUSION: This study showed that 30% of the adolescents with chronic diseases had major discrepancies between clinical diagnosis of death and autopsy findings. Pneumonia, pulmonary abscess, as well as isolation of yeast and virus were more frequently identified at autopsy findings in the groups with major discrepancies.

Health-related quality of life and functionality in primary caregiver of surviving pediatric COVID-19.

Objectives: To prospectively assess health-related quality of life (HRQoL), global functionality, and disability in primary caregivers of surviving children and adolescents after COVID-19. Methods: A longitudinal observational study was carried out on primary caregivers of surviving pediatric post-COVID-19 patients (n = 51) and subjects without COVID-19 (n = 60). EuroQol five-dimension five-level questionnaire (EQ-5D-5L) and 12-question WHO Disability Assessment Schedule 2.0 (WHODAS 2.0) were answered for both groups. The univariate regression analysis was carried out using SPSS (v 20) and significance was established at 5%. Results: The median duration between COVID-19 diagnosis in children and adolescents and longitudinal follow-up visits was 4.4 months (0.8-10.7). The median age of children and adolescents caregivers with laboratory-confirmed COVID-19 was similar to primary caregivers of subjects without laboratory-confirmed COVID-19 [43.2 (31.6-60.9) vs. 41.5 (21.6-54.8) years, p = 0.08], as well as similar female sex (p = 1.00), level of schooling (p = 0.11), social assistance program (p = 0.28), family income/month U$ (p = 0.25) and the number of household's members in the residence (p = 0.68). The frequency of slight to extreme problems (level ≥ 2) of the pain/discomfort domain according to EQ-5D-5L score was significantly higher in the former group [74% vs. 52.5%, p = 0.03, OR = 2.57 (1.14-5.96)]. The frequency of disability according to WHODAS 2.0 total score was similar to those without disability and unknown (p = 0.79); however, with a very high disability in both groups (72.5% and 78.3%). Further analysis of primary caregivers of children and adolescents with post-COVID-19 condition (PCC) [n = 12/51 (23%)] compared to those without PCC [n = 39/51(77%)] revealed no differences between demographic data, EQ-5D-5L and WHODAS 2.0 scores in both groups (p > 0.05). Conclusion: We longitudinally demonstrated that pain/discomfort were predominantly reported in approximately 75% of primary caregiver of COVID-19 patients, with high disability in approximately three-quarters of both caregiver groups. These data emphasized the prospective and systematic caregiver burden evaluation relevance of pediatric COVID-19.

Simultaneous occurrence of biphenotypic T cell/myeloid lesions involving t(12;13)(p13;q14) in a pediatric patient.

This paper chronicles a 2-year-old girl who presented with acute leukemia/lymphoma syndrome of the T cell immunophenotype. At this time, the cytogenetic analysis of her bone marrow cells showed a reciprocal translocation between the short arm of chromosome 12 and the long arm of chromosome 13, t(12;13)(p13;q14). The immunophenotyping of bone marrow blast cells by flow cytometry revealed a population of cells positive for CD56, CD117, CD45, partial CD33, partial HLA-DR, CD13, CD7, CD2 and CD5. Therefore, a diagnosis of acute leukemia with a mixed T cell/myeloid phenotype was made. The patient had a poor response to classic T cell acute lymphocytic leukemia/lymphoma therapy; thus, her treatment was changed to a myeloid leukemia protocol, which produced a good response. She underwent a successful cord blood transplantation from an unrelated HLA partially matched donor. The coexistence of these two phenotypes prompts questions about the existence of clonal instability, which might influence the choice of therapy. The rarity of the t(12;13)(p13;q14) and the coexistence of T cell/myeloid markers suggest a nonrandom association. To the best of our knowledge, this is the first reported case in which a cell clone bearing a t(12;13)(p13;q14) translocation in a mixed T cell/myeloid lesion was detected.

Does adjunctive chemotherapy reduce remission rates compared to cortisone alone in unifocal or multifocal histiocytosis of bone?

BACKGROUND: Langerhans cell histiocytosis (LCH) is a rare disorder that can affect almost any organ, including bone. Treatment options include local corticosteroid infiltration in isolated bone lesions and oral corticosteroids and chemotherapy in multifocal bone lesions. Several studies show local corticosteroid injection in unifocal bone lesions heal in more than 75% of patients with minimal side effects. Therefore, it is unclear whether chemotherapy adds materially to the healing rate. QUESTIONS/PURPOSES: We therefore compared overall survival, remission rate, and recurrence rate in patients with bone LCH treated with chemotherapy and corticosteroids or corticosteroids alone. METHODS: We retrospectively reviewed the records of 198 patients with LCH since 1950. Median age at diagnosis was 5 years, male-to-female ratio was 1.33, and the most frequent symptom was local pain (95%). We recorded the disease presentation, demographics, treatment, and clinical evolution of each patient. Minimum followup was 4 months (median, 24 months; range, 4-360 months). RESULTS: The survival rate of the systemic disease group was 76.5% (65 of 85) while the survival rate in the unifocal and multifocal bone involvement groups was 100% at a median 5-year followup. All patients with unifocal bone involvement and 40 of 43 (93%) with multifocal bone involvement had complete remission. One of 30 patients with multifocal bone involvement treated with chemotherapy and oral corticosteroids did not achieve remission whereas two of six receiving only corticosteroids did not achieve remission. CONCLUSIONS: Our observations suggest intralesional corticosteroid injection without adjunctive chemotherapy achieves remission in unifocal bone LCH but may not do so in multifocal single-system bone involvement. Larger series would be required to confirm this observation. LEVEL OF EVIDENCE: Level IV, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence.

P-glycoprotein expression, tumor weight, age, and relapse in patients with stage I and II favorable-histology Wilms' tumor.

Fifteen percent of patients with Wilms' tumor (WT) experience relapse. It has been suggested that weight and age may affect the chances of relapse. Few studies have investigated the role, if any, between P-glycoprotein (P-gp) and relapse. The authors assessed the prognostic value of tumor weight and age at diagnosis and asked whether some other potential biological markers, specifically P-gp protein expression, had a prognostic value in favorable-histology WT. No association between age and relapse could be found. Patients with tumor weight ≥550 g were 6 times more likely to relapse, whereas P-gp expression was positive in 18/40 (45%) of the patients, of which 10/12 (83.3%) relapsed and 8/28 (28.6%) did not. Further studies are necessary to elucidate whether or not P-gp is related to relapse in patients with histologically favorable Wilms' tumor. If confirmed, the protein may be used in the future as a target for new drugs and treatments for this group of patients.

PEDIATRICIANS AFTER RESIDENCY: A SURVEY OF PERSONAL/PROFESSIONAL DATA AND ISSUES.

OBJECTIVE: To assess personal, professional, medical, and scientific educational characteristics and issues reported by pediatricians. METHODS: Cross-sectional study based on an online survey including 614 pediatricians who graduated in the last 15 years at a University Pediatric Department in Brazil. RESULTS: The response rate was 331/614(54%). The majority were females (82%), the median age was 33 years (27-40) and median years of pediatric practice was 5 (1-13). High workload (>60 hours/week) occurred in 25% and 47% earned ≥15 minimum wages/month. The most work-related issues reported were long working hours, poor social life and a sedentary lifestyle (>50%). Pediatricians were further divided into two groups, according to years of pediatric clinical practice: group 1 (≤5 years) and group 2 (>5 years). The median of overall satisfaction with pediatric residency [8(0-10) vs. 9 (4-10); p=0.002] was significantly reduced in group 1. The frequencies of workload >60 hours, work on pediatric ward and pediatric intensive care were significantly higher in the first group (p<0.05). Regarding main issues related to clinical practice in the last year, long working hours (73 vs. 53%; p<0.001), poor social life (75 vs. 62%; p=0.018) and harassment (23 vs. 4%; p=0.003) were significantly higher in the first group. CONCLUSIONS: Very early career pediatricians (≤5 years) reported higher workload, lower income, work-related issues and different location of pediatric practice compared to early career pediatricians (>5 years). The overall satisfaction with pediatric residency was good, however, reduced in very early career pediatricians.

Differences in children and adolescents with SARS-CoV-2 infection: a cohort study in a Brazilian tertiary referral hospital.

OBJECTIVES: To compare demographic/clinical/laboratory/treatments and outcomes among children and adolescents with laboratory-confirmed coronavirus disease 2019 (COVID-19). METHODS: This was a cross-sectional study that included patients diagnosed with pediatric COVID-19 (aged <18 years) between April 11, 2020 and April 22, 2021. During this period, 102/5,951 (1.7%) of all admissions occurred in neonates, children, and adolescents. Furthermore, 3,962 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) detection samples were processed in patients aged <18 years, and laboratory-confirmed COVID-19 occurred in 155 (4%) inpatients and outpatients. Six/155 pediatric patients were excluded from the study. Therefore, the final group included 149 children and adolescents (n=97 inpatients and 52 outpatients) with positive SARS-CoV-2 results. RESULTS: The frequencies of sore throat, anosmia, dysgeusia, headache, myalgia, nausea, lymphopenia, pre-existing chronic conditions, immunosuppressive conditions, and autoimmune diseases were significantly reduced in children and adolescents (p<0.05). Likewise, the frequencies of enoxaparin use (p=0.037), current immunosuppressant use (p=0.008), vasoactive agents (p=0.045), arterial hypotension (p<0.001), and shock (p=0.024) were significantly lower in children than in adolescents. Logistic regression analysis showed that adolescents with laboratory-confirmed COVID-19 had increased odds ratios (ORs) for sore throat (OR 13.054; 95% confidence interval [CI] 2.750-61.977; p=0.001), nausea (OR 8.875; 95% CI 1.660-47.446; p=0.011), and lymphopenia (OR 3.575; 95% CI 1.355-9.430; p=0.010), but also had less hospitalizations (OR 0.355; 95% CI 0.138-0.916; p=0.032). The additional logistic regression analysis on patients with preexisting chronic conditions (n=108) showed that death as an outcome was significantly associated with pediatric severe acute respiratory syndrome (SARS) (OR 22.300; 95% CI 2.341-212.421; p=0.007) and multisystem inflammatory syndrome in children (MIS-C) (OR 11.261; 95% CI 1.189-106. 581; p=0.035). CONCLUSIONS: Half of the laboratory-confirmed COVID-19 cases occurred in adolescents. Individuals belonging to this age group had an acute systemic involvement of SARS-CoV-2 infection. Pediatric SARS and MIS-C were the most important factors associated with the mortality rate in pediatric chronic conditions with COVID-19.

Persistent symptoms and decreased health-related quality of life after symptomatic pediatric COVID-19: A prospective study in a Latin American tertiary hospital.

OBJECTIVES: To prospectively evaluate demographic, anthropometric and health-related quality of life (HRQoL) in pediatric patients with laboratory-confirmed coronavirus disease 2019 (COVID-19). METHODS: This was a longitudinal observational study of surviving pediatric post-COVID-19 patients (n=53) and pediatric subjects without laboratory-confirmed COVID-19 included as controls (n=52) was performed. RESULTS: The median duration between COVID-19 diagnosis (n=53) and follow-up was 4.4 months (0.8-10.7). Twenty-three of 53 (43%) patients reported at least one persistent symptom at the longitudinal follow-up visit and 12/53 (23%) had long COVID-19, with at least one symptom lasting for >12 weeks. The most frequently reported symptoms at the longitudinal follow-up visit were headache (19%), severe recurrent headache (9%), tiredness (9%), dyspnea (8%), and concentration difficulty (4%). At the longitudinal follow-up visit, the frequencies of anemia (11% versus 0%, p=0.030), lymphopenia (42% versus 18%, p=0.020), C-reactive protein level of >30 mg/L (35% versus 0%, p=0.0001), and D-dimer level of >1000 ng/mL (43% versus 6%, p=0.0004) significantly reduced compared with baseline values. Chest X-ray abnormalities (11% versus 2%, p=0.178) and cardiac alterations on echocardiogram (33% versus 22%, p=0.462) were similar at both visits. Comparison of characteristic data between patients with COVID-19 at the longitudinal follow-up visit and controls showed similar age (p=0.962), proportion of male sex (p=0.907), ethnicity (p=0.566), family minimum monthly wage (p=0.664), body mass index (p=0.601), and pediatric pre-existing chronic conditions (p=1.000). The Pediatric Quality of Live Inventory 4.0 scores, median physical score (69 [0-100] versus 81 [34-100], p=0.012), and school score (60 [15-100] versus 70 [15-95], p=0.028) were significantly lower in pediatric patients with COVID-19 at the longitudinal follow-up visit than in controls. CONCLUSIONS: Pediatric patients with COVID-19 showed a longitudinal impact on HRQoL parameters, particularly in physical/school domains, reinforcing the need for a prospective multidisciplinary approach for these patients. These data highlight the importance of closer monitoring of children and adolescents by the clinical team after COVID-19.

Impact of Pediatric Hematopoietic Stem-Cell Transplantation on Craniofacial Growth.

OBJECTIVES: To assess the craniofacial skeletal growth in pediatric hematopoietic stem-cell transplantation (HSCT) survivors in comparison with age-sex matched-paired controls. METHODS: A case-controlled retrospective comparison of the craniofacial growth in 25 HSCT children and 25 matched-paired controls was conducted. Craniofacial growth was quantitatively assessed by linear and angular measurements in panoramic radiographic images using ImageJ¯. Stature growth and body weight were obtained through physical examination. Cancer diagnosis, myeloablative conditioning, and HSCT were retrieved from medical records. RESULTS: Patients aged 12.2 years (±3.8; 16 male, 9 female). Radiographic images were obtained on an average of 2.43 (±2.0) years after HSCT. The main malignant diagnosis was acute lymphoblastic leukemia (56%), followed by acute myeloid leukemia (36%) and myelodysplastic syndromes (8%). Total body irradiation was associated with chemotherapy at 80%. Mean age at transplantation was 10 (±4.7) years. HSCT survivors showed reduced a vertical growth of the mandibular ramus (p=0.003). This persisted among individuals below 12 years of age (p=0.017). The HSCT group showed delayed dental eruption, though there was no statistically significant difference (p=0.3668). The HSCT group showed stature deficit, increased weight, and body mass index (Z-score stature: -0.28; Z-score weight: 0.38, respectively). CONCLUSIONS: Pediatric HSCT has decreased vertical craniofacial growth compared to their matched controls. There might be an association between reduced craniofacial vertical growth and reduced estature growth. Further studies to quantitatively investigate the impact of different myeloablative regimens in craniofacial skeletal growth and development.

Brainstem auditory pathway of children with acute lymphoid leukemia on chemotherapy with methotrexate.

OBJECTIVE: Investigate the auditory pathway in the brainstem of children with acute lymphoblastic leukemia submitted to chemotherapy (by intravenous or intrathecal infusion). METHODS: Fourteen children aged between 2 and 12 years with diagnosis of acute lymphoid leukemia were evaluated. The following procedures were used: meatoscopy, acoustic immitance measurements, tonal audiometry, vocal audiometry, transient otoacoustic emissions, and auditory brainstem response. RESULTS: From the 14 children with normal auditory thresholds, 35.71% showed an alteration in auditory brainstem response, with a predominance of hearing impairment in the lower brainstem. It was found that 80% of the children with alteration had used intrathecal methotrexate less than 30 days and that 40% had the highest cumulative intravenous methotrexate doses. CONCLUSION: Children with acute lymphoblastic leukemia submitted to chemotherapy, present auditory pathway impairment in the brainstem, with a predominance of a low brainstem.

Profile of health professionals who completed a master's, doctoral, or post-doctoral degree in one Brazilian pediatric program.

OBJECTIVE: This study aimed to determine the personal and professional characteristics, and the physical, psychiatric/psychological, and professional issues that exist among master's-, doctoral-, and post-doctoral-level health professionals. METHODS: A cross-sectional, online, self-reported survey of 452 postgraduates who completed master's, doctoral, or post-doctoral degrees in one graduate program in pediatrics in São Paulo, Brazil, was conducted. RESULTS: The response rate was 47% (211/453). The majority of participants were women (78%) and physicians (74%), and the median age was 47 years (28-71). Master's, doctoral, and post-doctoral degrees were reported by 73%, 53%, and 3%, respectively. High workload (>40 hours/week) occurred in 59%, and 45% earned ≥15 minimum wages/month. At least one participation in scientific meeting in the past year was reported by 91%, and 79% had published their research. Thirty-nine percent served as a member of a faculty of an institution of higher learning. The data were analyzed by two age groups: participants aged ≤48 years (group 1) and participants aged >48 years (group 2). The median rating of overall satisfaction with the profession in the past year [8 (0-10) vs. 9 (1-10), p=0.0113]; workload >40 hours/week (53% vs. 68%, p=0.034); and ≥15 minimum wages/month (37% vs. 56%, p=0.0083) were significantly lower in group 1. Further analysis by gender revealed that the median rating of overall satisfaction with the profession in the past year [8 (0-10) vs. 9 (3-10), p=0.0015], workload >40 hours/week (53% vs. 83%, p=0.0002), and ≥15 minimum wages/month (37% vs. 74%, p=0.0001) were significantly lower in women compared with men. The median rating of overall satisfaction with the mentorship supervision provided was significantly higher among the women 10 (5-10) vs. 10 (2-10), p=0.0324]. CONCLUSIONS: The majority of master's-, doctoral-, and post-doctoral-level health professionals were women and physicians, and had published their thesis. Younger postgraduates and women reported low salaries, less likelihood of working >40 hours/week, and less overall satisfaction with their profession. Further longitudinal and qualitative studies are warranted to assess career trajectories after graduation.

COMPLEXITY OF PEDIATRIC CHRONIC DISEASE: CROSS-SECTIONAL STUDY WITH 16,237 PATIENTS FOLLOWED BY MULTIPLE MEDICAL SPECIALTIES.

OBJECTIVE: To assess demographic data and characteristics of children and adolescents with pediatric chronic diseases (PCD), according to the number of specialties/patient. METHODS: We performed a cross-sectional study with 16,237 PCD patients at outpatient clinics in one year. Data were analyzed by an electronic data system, according to the number of physician appointments for PCD. This study assessed: demographic data, follow-up characteristics, types of medical specialty, diagnosis (International Statistical Classification of Diseases and Related Health Problems - ICD-10), number of day hospital clinic visits, and acute complications. RESULTS: Patients followed by ≥3 specialties simultaneously showed a significantly higher duration of follow-up compared to those followed by ≤2 specialties [2.1 (0.4-16.4) vs. 1.4 (0.1-16.2) years; p<0.001] and a higher number of appointments in all specialties. The most prevalent medical areas in patients followed by ≥3 specialties were: Psychiatry (Odds Ratio - OR=8.0; confidence interval of 95% - 95%CI 6-10.7; p<0.001), Palliative/Pain Care (OR=7.4; 95%CI 5.7-9.7; p<0.001), Infectious Disease (OR=7.0; 95%CI 6.4-7.8; p<0.001) and Nutrology (OR=6.9; 95%CI 5.6-8.4; p<0.001). Logistic regressions demonstrated that PCD patients followed by ≥3 specialties were associated with high risk for: number of appointments/patient (OR=9.2; 95%CI 8.0-10.5; p<0.001), day hospital clinic visits (OR=4.8; 95%CI 3.8-5.9; p<0.001), emergency department visits (OR=3.2; 95%CI 2.9-3.5; p<0.001), hospitalizations (OR=3.0; 95%CI 2.7-3.3; p<0.001), intensive care admissions (OR=2.5; 95%CI 2.1-3.0; p<0.001), and deaths (OR=2.8; 95%CI 1.9-4.0; p<0.001). The diagnosis of asthma, obesity, chronic pain, and transplant was significantly higher in patients followed by ≥3 specialties. CONCLUSIONS: The present study showed that PCD patients who required simultaneous care from multiple medical specialties had complex and severe diseases, with specific diagnoses.

Caesarean sections, prenatal and postnatal conditions and childhood acute lymphoblastic leukaemia: A case-control study in the State of São Paulo, Brazil.

INTRODUCTION: Brazil has high rates of caesarean sections, which has been suggested as a risk factor for acute lymphoblastic leukaemia (ALL). In addition, some pre- and postnatal conditions have been identified as relevant in the etiology of ALL. OBJECTIVES: Investigate the association of caesarean sections, pre- and postnatal conditions with childhood ALL in the State of São Paulo. METHODS: Population-based case-control study including children that are below10 years old. Information on study variables was obtained through face to face interviews, through a questionnaire, and the State of São Paulo Declarations of Live Births database. The conditional and unconditional logistic regression approaches were used to calculate the odds ratio (OR) of the associations between caesarean sections, pre- and postnatal conditions with ALL, and 95 % confidence intervals (95 % CI). RESULTS: We observed a weak and non-statistically significant risk for ALL among children exposed to caesarean sections (unconditional logistic regression OR 1.08; 95 % CI 0.70-1.66; conditional logistic regression OR 1.21; 95 % CI 0.72-2.02), but among children under 3 years old and born through a caesarean sections, the risk of ALL was greater (unconditional logistic regression OR 1.70; 95 % CI 0.69-4.21). A negative association for ALL was observed among children with mothers who reported 12 years of schooling or more (unconditional logistic regression OR 0.34; 95 % CI 0.16-0.69). CONCLUSIONS: We found a tenuous suggestive association between caesarean sections and childhood ALL. The mother's high level of education showed an inverse association with ALL.