Economic impact of advanced pediatric cancer on families

Despite emerging evidence of substantial financial distress in families of children with complex illness, little is known about economic hardship in families of children with advanced cancer.

Disparities in pediatric leukemia early survival in Argentina: a population-based study

To identify disparities-using recursive partitioning (RP)-in early survival for children with leukemias treated in Argentina, and to depict the main characteristics of the most vulnerable groups.

Epigenetic deregulation in pediatric acute lymphoblastic leukemia

Similar to most cancers, genome-wide DNA methylation profiles are commonly altered in pediatric acute lymphoblastic leukemia (ALL); however, recent observations highlight that a large portion of malignancy-associated DNA methylation alterations are not accompanied by related gene expression changes. By analyzing and integrating the methylome and transcriptome profiles of pediatric B-cell ALL cases and primary tissue controls, we report 325 genes hypermethylated and downregulated and 45 genes hypomethylated and upregulated in pediatric B-cell ALL, irrespective of subtype. Repressed cation channel subunits and cAMP signaling activators and transducers are overrepresented, potentially indicating a reduced cellular potential to receive and propagate apoptotic signals. Furthermore, we report specific DNA methylation alterations with concurrent gene expression changes within individual ALL subtypes. The ETV6-RUNX1 translocation was associated with downregulation of ASNS and upregulation of the EPO-receptor, while Hyperdiploid patients (> 50 chr) displayed upregulation of B-cell lymphoma (BCL) members and repression of PTPRG and FHIT. In combination, these data indicate genetically distinct B-cell ALL subtypes contain cooperative epimutations and genome-wide epigenetic deregulation is common across all B-cell ALL subtypes.

Social competence following pediatric stroke: contributions of brain insult and family environment

Limited information is available regarding predictors of psychosocial difficulties in children following stroke. This study aimed to (i) compare social competence of children with arterial ischemic stroke (AIS) to those with chronic illness and healthy controls and (ii) investigate the contribution of stroke pathology, neurological outcome and environment. Thirty-six children with AIS > 12 months prior to recruitment were compared with children with chronic illness (asthma) (n = 15) and healthy controls (n = 43). Children underwent intellectual assessment, and children and parents completed questionnaires to assess social competence. Children with AIS underwent MRI scan and neurological evaluation. Child AIS was associated with poorer social adjustment and participation, and children with AIS were rated as having more social problems than controls. Lesion volume was not associated with social outcome, but subcortical stroke was linked to reduced social participation and younger stroke onset predicted better social interaction and higher self-esteem. Family function was the sole predictor of social adjustment. Findings highlight the risk of social impairment following pediatric stroke, with both stroke and environmental factors influencing children's social competence in the chronic stages of recovery. They indicate the potential for intervention targeting support at the family level.

Environmental contributions to social and mental health outcomes following pediatric stroke

Mental health and social outcomes following acquired brain injury (ABI) in children are often considered to be due to brain insult, but other factors, such as environment, may also play a role. We assessed mental health and social function in children with chronic illness, with and without stroke (a form of ABI), and typically developing (TD) controls to examine environmental influences on these outcomes. We recruited 36 children diagnosed with stroke, 15 with chronic asthma, and 43 TD controls. Children and parents completed questionnaires rating child mental health and social function and distal and proximal environment. TD children had significantly less internalizing and social problems than stroke and asthma groups, and engaged in more social activities than children with stroke. Poorer parent mental health predicted more internalizing and social problems and lower social participation. Family dysfunction was associated with internalizing problems. Lower parent education contributed to children's social function. Children with chronic illness are at elevated risk of poorer mental health and social function. Addition of brain insult leads to poorer social participation. Quality of home environment contributes to children's outcomes, suggesting that supporting parent and family function provides an opportunity to optimize child mental health and social outcomes.

Emergence agitation in pediatric anesthesia: current features

Objective: Postoperative agitation in children is a well-documented clinical phenomenon with incidence ranging from 10% to 67%. There is no definitive explanation for this agitation. Possible causes include rapid awakening in unfamiliar settings, pain (wounds, sore throat, bladder distension, etc.), stress during induction, hypoxemia, airway obstruction, noisy environment, anesthesia duration, child's personality, premedication and type of anesthesia. The purpose of this paper is to discuss the possible causes of postoperative agitation in children, providing a foundation for better methods of identifying and preventing this problem.Sources: MEDLINE and PubMed were searched using the following words: emergence, agitation, incidence, etiology, diagnosis, treatment, children, pediatric, anesthesia.Summary of the findings: This study includes a review of potential agitation trigger factors and a proposal for a standardized diagnostic score system, in addition to measures to improve prevention and treatment.Conclusion: No single factor can identified as the cause of postoperative agitation, which should therefore be considered a syndrome made up of biological, pharmacological, psychological and social components, and which anesthesiologists and pediatric intensive care specialists should be prepared to identify, prevent and intervene appropriately as necessary.

Intraoperative lactate levels and postoperative complications of pediatric cardiac surgery

Objectives: Correlate arterial lactate levels during the intraoperative period of children undergoing cardiac surgery and the occurrence of complications in the postoperative period. Aim: Arterial lactate levels can indicate hypoperfusion states, serving as prognostic markers of morbidity and mortality in this population. Background: Anesthesia for cardiac pediatric surgery is frequently performed on patients with serious abnormal physiological conditions. During the intraoperative period, there are significant variations of blood volume, body temperature, plasma composition, and tissue blood flow, as well as the activation of inflammation, with important pathophysiological consequences. Methods/Materials: Chart data relating to the procedures and perioperative conditions of the patients were collected on a standardized form. Comparisons of arterial lactate values at the end of the intraoperative period of the patients that presented, or not, with postoperative complications and frequencies related to perioperative conditions were established by odds ratio and nonparametric univariate analysis. Results: After surgeries without cardiopulmonary bypass (CPB), higher levels of arterial lactate upon ICU admission were observed in patients who had renal complications (2.96 vs 1.31 mm) and those who died (2.93 vs 1.40 mm). For surgeries with CPB, the same association was observed for cardiovascular (2.90 mm x 2.06 mm), renal (3.34 vs 2.33 mm), respiratory (2.98 vs 2.12 mm) and hematological complications (2.99 vs 1.95 mm), and death (3.38 vs 2.40 mm). Conclusion: Elevated intraoperative arterial lactate levels are associated with a higher morbidity and mortality in low- and medium-risk procedures, with or without CPB, in pediatric cardiac surgery.

Anesthesia-related mortality in pediatric patients: a systematic review

This systematic review of the Brazilian and worldwide literature aimed to evaluate the incidence and causes of perioperative and anesthesia-related mortality in pediatric patients. Studies were identified by searching EMBASE (1951-2011), PubMed (1966-2011), LILACS (1986-2011), and SciElo (1995-2011). Each paper was revised to identify the author(s), the data source, the time period, the number of patients, the time of death, and the perioperative and anesthesia-related mortality rates. Twenty trials were assessed. Studies from Brazil and developed countries worldwide documented similar total anesthesia-related mortality rates (<1 death per 10,000 anesthetics) and declines in anesthesia-related mortality rates in the past decade. Higher anesthesia-related mortality rates (2.4-3.3 per 10,000 anesthetics) were found in studies from developing countries over the same time period. Interestingly, pediatric perioperative mortality rates have increased over the past decade, and the rates are higher in Brazil (9.8 per 10,000 anesthetics) and other developing countries (10.7-15.9 per 10,000 anesthetics) compared with developed countries (0.41-6.8 per 10,000 anesthetics), with the exception of Australia (13.4 per 10,000 anesthetics). The major risk factors are being newborn or less than 1 year old, ASA III or worse physical status, and undergoing emergency surgery, general anesthesia, or cardiac surgery. The main causes of mortality were problems with airway management and cardiocirculatory events. Our systematic review of the literature shows that the pediatric anesthesia-related mortality rates in Brazil and in developed countries are similar, whereas the pediatric perioperative mortality rates are higher in Brazil compared with developed countries. Most cases of anesthesiarelated mortality are associated with airway and cardiocirculatory events. The data regarding anesthesia-related and perioperative mortality rates may be useful in developing prevention strategies.

Thorax ultrasound in the management of pediatric pneumonias complicated with empyema

The aim of this work is to prospectively study the value of thoracic ultrasound (US) before pleural drainage in children with parapneumonic effusion (PPE). All children hospitalized for PPE, identified by thoracic radiography, underwent US to assess pleural loculation, echogenicity, and pleural fluid quantity. From August 2001 to July 2003, 52 children were examined. US was performed on 48 of these children, of whom 35 received chest tube drainage and 13 only received clinical treatment. US identified 38 patients with free flowing and 10 with loculated pleural fluid. About 25 of the free flowing (65.8%) and 10 (100%) of the loculated patients received chest tube drainage. Echogenicity was anechoic in 13, echoic without septations in 17 and echoic with septations in 18. Chest tube drainage was required in 6 anechoic (46.15%), 14 echoic without septations (82.35%), and 15 echoic with septations (83.33%). Quantity of fluid estimated by US varied from 20 to 860 ml. Effusion volume was higher in patients that were echoic with septations and loculated effusions. Pleural glucose and pH were lower, and LDH was higher in loculated PPE patients. In conclusion, US is an auxiliary exam for determining whether thoracic drainage is needed in parapneumonic effusion; loculated or echoic effusion should be drained, and free anechoic fluid needs further investigation.

Cytogenetic studies of Brazilian pediatric myelodysplastic syndrome cases: challenges and difficulties in a large and emerging country

Myelodysplastic syndromes (MDS) and juvenile myelomonocytic leukemia (JMML) are rare hematopoietic stem cell diseases affecting children. Cytogenetics plays an important role in the diagnosis of these diseases. We report here the experience of the Cytogenetic Subcommittee of the Brazilian Cooperative Group on Pediatric Myelodysplastic Syndromes (BCG-MDS-PED). We analyzed 168 cytogenetic studies performed in 23 different cytogenetic centers; 84 of these studies were performed in patients with confirmed MDS (primary MDS, secondary MDS, JMML, and acute myeloid leukemia/MDS+Down syndrome). Clonal abnormalities were found in 36.9% of the MDS cases and cytogenetic studies were important for the detection of constitutional diseases and for differential diagnosis with other myeloid neoplasms. These data show the importance of the Cooperative Group for continuing education in order to avoid a late or wrong diagnosis.

Mitochondrial Alterations in Nonalcoholic Fatty Liver Disease. Pediatric Case Description of Three Submitted Sequential Biopsies

Nonalcoholic fatty liver disease (NAFLD) is a clinical-pathological syndrome that encompasses a wide spectrum of morphologic alterations, ranging from simple hepatic steatosis to a more severe stage, known as nonalcoholic steatohepatitis (NASH). The purpose of this clinical report was to contribute to the understanding of mitochondrial alterations in NAFLD. The child (13-month-old) underwent initial biopsy in the year 2000 and was diagnosed with diffuse macro and microvesicular steatosis. Two additional biopsies were performed in 2001 and 2004. A high percentage of microvesicular steatosis was observed in the biopsies performed in 2000 and 2001. Mitochondrial size was slightly increased in the biopsy performed in the year 2000, significantly increased in 2001 and decreased in 2004. The presence of "mitochondrial hypertrophy" in the hepatocytes of an asymptomatic pediatric patient whose disease presentation was typical of NAFLD, excluding other pathological processes, allowed us to suspect that such a defect was considered the primary mitochondrial disorder.

Steatosis of indeterminate cause in a pediatric group: is it a primary mitochondrial hepatopathy?

CONTEXTO E OBJETIVO: em crianças, a esteatose hepática pode se relacionar a erros inatos do metabolismo (EIMs) ou à doença hepática gordurosa não-alcoólica (DHGNA). O objetivo deste estudo foi avaliar e caracterizar esteatose de causa indeterminada por meio de análises morfológica e morfométrica em tecido hepático. TIPO DE ESTUDO E LOCAL: Estudo transversal nos Departamentos de Patologia da Faculdade de Ciências Médicas da Universidade Estadual de Campinas (FCM-Unicamp) e Faculdade de Medicina de Botucatu da Universidade Estadual Paulista (FMB-Unesp). MÉTODOS: Foram utilizadas 18 biópsias hepáticas consecutivas obtidas de 16 pacientes com idade variando de 3 meses a 12 anos e 9 meses, inseridas num banco de dados no período do estudo, que foram analisadas por microscopia óptica e eletrônica. Na microscopia eletrônica, foi realizada determinação da densidade mitocondrial e da área superficial média das mitocôndrias nos hepatócitos. Dez pacientes com idade variando de 1 a 14 anos foram usados como grupo controle. RESULTADOS: Foi detectada esteatose pura, não acompanhada por fibrose ou outra alteração histológica. Foi verificado que, na predominância de esteatose microvesicular, houve aumento significativo da área mitocondrial média. CONCLUSÃO: A esteatose microvesicular pode estar relacionada à hepatopatia mitocondrial primária, principalmente devido à redução na β-oxidação ou parcial estagnação da fosforilação oxidativa. Por essas razões, esta forma de esteatose (que não pode ser chamada de pura) possivelmente represente uma fase inicial no amplo espectro da DHGNA. Chamamos a atenção para casos de esteatose no grupo pediátrico com predomínio da forma microvesicular, uma vez que pode haver associação com desordens mitocondriais.

Long-Term Safety and Efficacy of Abatacept in Children With Juvenile Idiopathic Arthritis

Objective. We previously documented that abatacept was effective and safe in patients with juvenile idiopathic arthritis (JIA) who had not previously achieved a satisfactory clinical response with disease-modifying antirheumatic drugs or tumor necrosis factor blockade. Here, we report results from the long-term extension (LTE) phase of that study.Methods. This report describes the long-term, open-label extension phase of a double-blind, randomized, controlled withdrawal trial in 190 patients with JIA ages 6-17 years. Children were treated with 10 mg/kg abatacept administered intravenously every 4 weeks, with or without methotrexate. Efficacy results were based on data derived from the 153 patients who entered the open-label LTE phase and reflect >= 21 months (589 days) of treatment. Safety results include all available open-label data as of May 7, 2008.Results. of the 190 enrolled patients, 153 entered the LTE. By day 589, 90%, 88%, 75%, 57%, and 39% of patients treated with abatacept during the double-blind and LTE phases achieved responses according to the American College of Rheumatology (ACR) Pediatric 30 (Pedi 30), Pedi 50, Pedi 70, Pedi 90, and Pedi 100 criteria for improvement, respectively. Similar response rates were observed by day 589 among patients previously treated with placebo. Among patients who had not achieved an ACR Pedi 30 response at the end of the open-label lead-in phase and who proceeded directly into the LTE, 73%, 64%, 46%, 18%, and 5% achieved ACR Pedi 30, Pedi 50, Pedi 70, Pedi 90, and Pedi 100 responses, respectively, by day 589 of the LTE. No cases of tuberculosis and no malignancies were reported during the LTE. Pneumonia developed in 3 patients, and multiple sclerosis developed in 1 patient.Conclusion. Abatacept provided clinically significant and durable efficacy in patients with JIA, including those who did not initially achieve an ACR Pedi 30 response during the initial 4-month open-label lead-in phase.

Preliminary Criteria for Global Flares in Childhood-Onset Systemic Lupus Erythematosus

Objective. To develop widely acceptable preliminary criteria of global flare for childhood-onset systemic lupus erythematosus (cSLE).Methods. Pediatric rheumatologists (n = 138) rated a total of 358 unique patient profiles with information about the cSLE flare descriptors from 2 consecutive visits: patient global assessment of well-being, physician global assessment of disease activity (MD-global), health-related quality of life, anti-double-stranded DNA antibodies, disease activity index scores, protein: creatinine (P:C) ratio, complement levels, and erythrocyte sedimentation rate (ESR). Based on 2,996 rater responses about the course of cSLE (baseline versus followup), the accuracy (sensitivity, specificity, and area under the receiver operating characteristic curve) of candidate flare criteria was assessed. An international consensus conference was held to rank these candidate flare criteria as per the American College of Rheumatology recommendations for the development and validation of criteria sets.Results. The highest-ranked candidate criteria considered absolute changes (Delta) of the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) or British Isles Lupus Assessment Group (BILAG), MD-global, P:C ratio, and ESR; flare scores can be calculated (0.5 x Delta SLEDAI + 0.45 x Delta P:C ratio + 0.5 x Delta MD-global + 0.02 x Delta ESR), where values of >= 1.04 are reflective of a flare. Similarly, BILAG-based flare scores (0.4 x Delta BILAG + Delta 0.65 x Delta P:C ratio + 0.5 + Delta MD-global + 0.02 x Delta ESR) of >= 1.15 were diagnostic of a flare. Flare scores increased with flare severity.Conclusion. Consensus has been reached on preliminary criteria for global flares in cSLE. Further validation studies are needed to confirm the usefulness of the cSLE flare criteria in research and for clinical care.