Long-Term Evaluation of Post-transplant Lymphoproliferative Disorders in Paediatric Heart Transplantation in Sao Paulo, Brazil.

We sought to better define the demographics and characteristics of post-transplant lymphoproliferative disorders (PTLD) in a cohort of paediatric OHT patients from a developing country. Data were collected from the Heart Institute, Sao Paulo, for all paediatric OHT recipients from October 1992 to October 2018. Group differences between the PTLD and non-PTLD cohorts were assessed by Fisher exact and Mann-Whitney U tests. Kaplan-Meier curves analysed the survival in each group. Data were reviewed for 202 paediatric OHT recipients. Overall 1-, 5- and 10-year survival for the entire cohort was 76.5%, 68.3% and 62.9%; 24 patients (11.9%) developed PTLD at a median 3.1 years (IQR 0.8-9.0) after OHT. Cases were evenly spread over the follow-up period, with PTLD diagnosed in 9.8% (n = 137) of patients who were alive at 3 years, 15.3% (n = 78) of patients who were alive at 5 years and 29.3% (n = 41) of patients who were alive at 10 years. The commonest form of PTLD was diffuse large B cell lymphoma (n = 9), and most patients received rituximab with immunosuppression and chemotherapy as treatment (n = 15). We identified no increased risk in mortality amongst the PTLD vs. non-PTLD cohorts in multivariate analysis (P = 0.365). PTLD after paediatric OHT had acceptable outcomes. However, risk factors for PTLD were not identified and warrant further investigation.

A longitudinal study of the peripheral and central auditory pathways in individuals with acute lymphoid leukemia.

OBJECTIVE: To characterize the peripheral and central auditory pathways in individuals with Acute Lymphoid Leukemia (ALL) and compare assessment results before and during chemotherapy. METHOD: The study included 17 subjects with ALL, divided into two age groups: 3 to 6 (11 individuals) and 7 to 16 years old (6 individuals). Each subject was evaluated twice (before and 3 to 6 months after chemotherapy treatment) with the following procedures: medical history survey, otoscopy, Pure-Tone Threshold (PTA) and speech audiometry, acoustic immittance measures, Brainstem Auditory Evoked Potentials (BAEP) and Long-Latency Auditory Evoked Potentials (LLAEP). RESULTS: PTA was normal. Tympanometry was abnormal in the second assessment in 2 individuals aged 3 to 6 years. One subject in each age group had absent ipsilateral acoustic reflexes. In high-frequency audiometry, 1 individual had abnormal results. BAEP was abnormal in 5 (first assessment) and 7 individuals (second assessment) aged 3 to 6 years and 2 (first assessment) and 1 individual (second assessment) aged 7 to 16 years. As for LLAEP, P1 latency was increased in 5 (first assessment) and 7 individuals (second assessment) aged 3 to 6 years. CONCLUSION: No hearing loss was identified in the behavioral audiological assessment. BAEP was more affected in the 3-to-6-year-old group, with greater impairment in the lower brainstem in the first and second assessments. In LLAEP, P1 was the most impaired component in children aged 3 to 6 years, and P2 and N2 were so for those 7 to 16 years old, especially in the second assessment.

Effects of a combined aerobic and strength training program in youth patients with acute lymphoblastic leukemia.

Cure rates of youth with Acute Lymphoblastic Leukemia (ALL) have increased in the past decades, but survivor's quality of life and physical fitness has become a growing concern. Although previous reports showed that resistance training is feasible and effective, we hypothesized that a more intense exercise program would also be feasible, but more beneficial than low- to moderate-intensity training programs. We aimed to examine the effects of an exercise program combining high-intensity resistance exercises and moderate-intensity aerobic exercises in young patients undergoing treatment for ALL. A quasi-experimental study was conducted. The patients (n = 6; 5-16 years of age) underwent a 12-week intra-hospital training program involving high-intensity strength exercises and aerobic exercise at 70% of the peak oxygen consumption. At baseline and after 12 weeks, we assessed sub-maximal strength (10 repetition-maximum), quality of life and possible adverse effects. A significant improvement was observed in the sub maximal strength for bench press (71%), lat pull down (50%), leg press (73%) and leg extension (64%) as a result of the training (p < 0.01). The parents' evaluations of their children's quality of life revealed an improvement in fatigue and general quality of life, but the children's self-reported quality of life was not changed. No adverse effects occurred. A 12-week in-hospital training program including high-intensity resistance exercises promotes marked strength improvements in patients during the maintenance phase of the treatment for Acute Lymphoblastic Leukemia without side-effects. Parents' evaluations of their children revealed an improvement in the quality of life. Key pointsPatients with ALL present low muscle strength and poor quality of life.High-intensity resistance exercises combined with moderate-intensity aerobic exercise improved muscle strength and quality of life during the maintenance phase of ALL treatment.The exercise training program seemed to be tolerable and safe in ALL patients.

The implementation of an online mindfulness-based program for pediatric patients at a tertiary hospital in South America: a feasibility study protocol.

BACKGROUND: The prevalence of chronic and complex pediatric health conditions has quickly risen over the last decades. Chronic and complex health conditions make pediatric patients and their families more susceptible to many distressing events during their lifespan. Mindfulness-based interventions have become a popular intervention for individuals living with chronic illnesses and have been adapted for pediatric populations with good results, including online versions. This study intends to report an implementation protocol of an online mindfulness-based program for adolescents to address an important gap in stress relief and health promotion for pediatric patients. METHODS: In this article, we describe the rationale and design of an implementation study of an online mindfulness-based program for pediatric patients at a tertiary pediatric hospital in South America. Participants will be recruited during one year to participate in an eight-session online mindfulness-based program. To assess our primary aim of feasibility, we will exam recruitment, retention and participation rates. Participants will also complete a symptomatology evaluation (i.e., depression, anxiety, and stress symptoms) at baseline and immediately at post-treatment and fidelity will be evaluated by a structured questionnaire. DISCUSSION: This study will be the first known to assess the implementation of an online mindfulness-based program for a pediatric population at a tertiary pediatric center in South America under real-life conditions. This study will establish the feasibility of a novel intervention aimed at promoting mental health and positive coping strategies among pediatric patients with chronic and complex health conditions. Evidence from this study would be useful to patients, families, clinicians, and policymakers and will help to devise strategies of health promotion for the pediatric population, as well as serve as a model for a future trial to examine efficacy of the proposed intervention. TRIAL REGISTRATION: This research has been registered at Ensaiosclinicos.gov.br , identifier RBR-23trp87 . Registered 25 February 2022-retrospectively registered.

Novel pathogenic variants and quantitative phenotypic analyses of Robinow syndrome: WNT signaling perturbation and phenotypic variability.

Robinow syndrome (RS) is a genetically heterogeneous disorder with six genes that converge on the WNT/planar cell polarity (PCP) signaling pathway implicated (DVL1, DVL3, FZD2, NXN, ROR2, and WNT5A). RS is characterized by skeletal dysplasia and distinctive facial and physical characteristics. To further explore the genetic heterogeneity, paralog contribution, and phenotypic variability of RS, we investigated a cohort of 22 individuals clinically diagnosed with RS from 18 unrelated families. Pathogenic or likely pathogenic variants in genes associated with RS or RS phenocopies were identified in all 22 individuals, including the first variant to be reported in DVL2. We retrospectively collected medical records of 16 individuals from this cohort and extracted clinical descriptions from 52 previously published cases. We performed Human Phenotype Ontology (HPO) based quantitative phenotypic analyses to dissect allele-specific phenotypic differences. Individuals with FZD2 variants clustered into two groups with demonstrable phenotypic differences between those with missense and truncating alleles. Probands with biallelic NXN variants clustered together with the majority of probands carrying DVL1, DVL2, and DVL3 variants, demonstrating no phenotypic distinction between the NXN-autosomal recessive and dominant forms of RS. While phenotypically similar diseases on the RS differential matched through HPO analysis, clustering using phenotype similarity score placed RS-associated phenotypes in a unique cluster containing WNT5A, FZD2, and ROR2 apart from non-RS-associated paralogs. Through human phenotype analyses of this RS cohort and OMIM clinical synopses of Mendelian disease, this study begins to tease apart specific biologic roles for non-canonical WNT-pathway proteins.

Nutritional status at diagnosis among children with cancer referred to a nutritional service in Brazil.

INTRODUCTION: Children and adolescents with cancer are particularly vulnerable to malnutrition and require special attention on nutritional assessment. An adequate nutritional status during treatment is essential in reducing morbidity and mortality, being a modifiable risk factor for clinical outcomes. This study aims to determine the nutritional status of pediatric patients with cancer assessed by the nutrition team at diagnosis and evaluate its association with the overall survival. METHOD: This is a retrospective cross-sectional study of patients at the time of cancer diagnosis who had nutritional assessments when hospitalized or referred to the nutrition outpatient clinic. Nutritional status was classified by the mid-upper arm circumference (MUAC) and body mass index for age z-score (zBMI/A). The Cox regression analysis was used to determine the association between the nutritional status and overall survival, adjusting for gender, tumor group and age. RESULTS: The study included 366 patients. The prevalence of undernutrition varied from 8 to 23% and overweight, from 5 to 20%. The MUAC identified more children as undernourished than the zBMI/A in patients with solid and hematological tumors. There was no significant difference in the overall survival by malnutrition classified by the zBMI/A (p =  0.1507) or MUAC (p =  0.8135). When adjusted for gender, tumor group and age, the nutritional status classification by the zBMI/A (hazard ratio [HR], 1.27; 95% confidence interval [CI], 0.88-1.83; p =  0.209) and MUAC (HR, 0.94; 95% CI, 0.61-1.44; p =  0.773) did not impact overall survival. CONCLUSION: The nutritional status at diagnosis did not significantly impact the overall survival, which suggests there may have been a protective effect by successful nutritional intervention during the subsequent care.

MUSIC INTERVENTIONS IN PEDIATRIC ONCOLOGY: Systematic review and meta-analysis.

BACKGROUND: Pain is a disagreeable and distressing feeling that affects human beings in multi-dimensional ways. A number of non-pharmacological interventions have had varying degrees of success in treating cancer-related pain, such as breathing and relaxation techniques, and music therapy, which have been identified as beneficial therapies for alleviating pain and anxiety. OBJECTIVE: Identify the therapeutic effects of music interventions in psychological and physiological terms and on the quality of life of children undergoing cancer treatment. METHOD: Systematic review of effectiveness based on the methodology of the Joanna Briggs Institute. RESULTS: Eleven articles were included with a total of 429 children, whose ages ranged from 0 to 18 years. The mean duration of the music intervention was 30.6 (±SD 9.8) min. In a combined estimate of five studies for pain and anxiety outcomes, there were benefits to using music when compared with the control group (SMD -1.05; CI 95 % -1.70 - 0.40 N = 453 I2 = 90 %). A combined analysis of five studies to assess quality of life showed that the use of music was favorable when compared with the control (SMD -0.80; CI 95 % -1.17-0.43 N = 457= I2 = 71 %). CONCLUSION: After completing this review, it was determined that there is evidence to support the use of music to reduce pain and anxiety and improve the quality of life of children undergoing cancer treatment.

Partnership of the Sociedade Brasileira de Oncologia Pediátrica and International Society of Pediatric Oncology to improve nutritional care for children with cancer in Brazil.

The authors present a proposal of a partnership between the Sociedade Brasileira de Oncologia Pediátrica (SOBOPE) and the International Society of Pediatric Oncology (SIOP) to promote the standardization and improvement of nutritional care of kids under cancer treatment in Brazil. The results of the first meeting in Brazil as well as plans for future meetings are described.

Development of a pilot telemedicine network for paediatric oncology in Brazil.

We established a pilot telemedicine network for paediatric oncology in Brazil, linking the School of Medicine at the University of Sao Paulo in Sao Paulo City to the 'Hospital de Base' in Porto Velho, Rondonia, located in the Amazon region, 3,000 km away. The videoconferencing link used ISDN transmission at 384 kbit/s. The network was used for patient screening, follow-up, treatment monitoring and other activities. Between March 2000 and 2002, 69 videoconferences were held for 33 patients, 29 with cancer. During this period, 16 patients required transfer, 18 patients died and 11 achieved cancer remission. The main cause for patient mortality (infection) was not one that could be addressed directly by telemedicine. Using the School of Medicine as a benchmark, the average mortality rate for paediatric cancer patients in the pilot was higher. However, it was lower than previous levels observed at Rondonia (62% versus 80%).

Establishment of the Brazilian telehealth network for paediatric oncology.

A telemedicine network has been established in Brazil to support distance medical practice in paediatric oncology. ONCONET comprises a national network of universities, research institutes and medical institutions. The system is Web-based and hosted on a high-performance computing infrastructure based on clusters of computers. It is based on open-source software, designed to provide high performance, fault tolerance and high availability. The ONCONET began operation in 2004. Currently, 30 hospitals affiliated to the Brazilian Society for Paediatric Oncology are users of the ONCONET. Six hospitals are connected by broadband access through the National Education and Research Network and 24 by conventional Internet access. The Multimedia Patients Registry also became operational in 2004, and its database contains information on 3,200 patients from the 30 hospitals. The technological platform was notable for its low production cost. It thus appears to be a sustainable solution to the problem of delivering continuing medical education in a large country with widely dispersed health professionals.

Web-based patient records and treatment guidelines in paediatric oncology.

We have established a Web-based system in Brazil offering health information in childhood cancer and services such as electronic patient records and treatment protocols. The system was based on open-source software. The database has records for about 3,200 patients from 30 Brazilian hospitals. An evaluation by doctors from the six hospitals comprising the Neuroblastoma Cooperative Group was positive, mainly because the system allows easy online access, but also because the electronic register performs data validation when information is inserted. Our experience shows that it is possible to use a Web-based system to provide paediatric cancer services at a distance.

Wilms tumor: a retrospective study of 32 patients using videolaparoscopic and open approaches.

OBJECTIVE: To compare videolaparoscopic nephrectomy and the open technique as treatments for Wilms tumor, specifically the surgical results, immediate and long-term complications, and patient survival. METHODS: A review of charts of children with unilateral Wilms tumor was performed. There were 2 surgical groups: (1) only open surgery and (2) videolaparoscopy. Complications, transfusion, ruptures, margins, conversions, lymph nodes, and relapse were analyzed. RESULTS: Seventeen children underwent laparoscopic nephrectomy and 15 underwent open nephrectomy. Mean surgical time was 164.71±26.07 minutes for the laparoscopic group, and there were no conversions or ruptures. The mean specimen weight was 145.01±105.85 g for the laparoscopic group and 257.40±162.70 g for the open surgery group. There was 1 preoperative rupture in the open surgery group. Transfusions were not required in either group. The surgical margins were positive in 1 of 17 cases (5.9%) in the laparoscopic group and in 3 of 15 cases (20%) in the open surgery group. One of the 17 (5.9%) laparoscopy-treated patients and 2 of the 15 open surgery-treated patients (13.3%) presented with local tumor relapse. The 5-year event-free survival rate was 93.3% (95% confidence interval, 0.61-0.99) for the laparoscopic group and 79.6% (95% confidence interval, 0.37-0.95] for the open surgery group (P=.446). CONCLUSION: Both techniques showed similar immediate and long-term results.

Minimally invasive adenocarcinoma of the lung in a young patient treated for osteosarcoma.

Although children with osteosarcoma have a higher incidence of a 2nd malignancy than the general population, its development in the lung is rare. The few reported cases belong to examples of carcinomas. Here we present the case of a 13-year-old boy with a primary pulmonary adenocarcinoma diagnosed 3 years after the osteosarcoma diagnosis and present a review of the literature.

Exposure to magnetic fields and childhood acute lymphocytic leukemia in São Paulo, Brazil.

BACKGROUND: Epidemiological studies have identified increased risks of leukemia in children living near power lines and exposed to relatively high levels of magnetic fields. Results have been remarkably consistent, but there is still no explanation for this increase. In this study we evaluated the effect of 60 Hz magnetic fields on acute lymphocytic leukemia (ALL) in the State of São Paulo, Brazil. METHODS: This case-control study included ALL cases (n=162) recruited from eight hospitals between January 2003 and February 2009. Controls (n=565) matched on gender, age, and city of birth were selected from the São Paulo Birth Registry. Exposure to extremely low frequency magnetic fields (ELF MF) was based on measurements inside home and distance to power lines. RESULTS: For 24h measurements in children rooms, levels of ELF MF equal to or greater than 0.3microtesla (µT), compared to children exposed to levels below 0.1 µT showed no increased risk of ALL (odds ratio [OR] 1.09; 95% confidence interval [95% CI] 0.33-3.61). When only nighttime measurements were considered, a risk (OR 1.52; 95% CI 0.46-5.01) was observed. Children living within 200 m of power lines presented an increased risk of ALL (OR 1.67; 95% CI 0.49-5.75), compared to children living at 600 m or more of power lines. For those living within 50 m of power lines the OR was 3.57 (95% CI 0.41-31.44). CONCLUSIONS: Even though our results are consistent with the small risks reported in other studies on ELF MF and leukemia in children, overall our results do not provide support for an association between magnetic fields and childhood leukemia, but small numbers and likely biases weaken the strength of this conclusion.