Fitness checklist model for spontaneous breathing tests in pediatrics.

OBJECTIVE: To evaluate whether a model of a daily fitness checklist for spontaneous breathing tests is able to identify predictive variables of extubation failure in pediatric patients admitted to a Brazilian intensive care unit. METHODS: This was a single-center, cross-sectional study with prospective data collection. The checklist model comprised 20 items and was applied to assess the ability to perform spontaneous breathing tests. RESULTS: The sample consisted of 126 pediatric patients (85 males (67.5%)) on invasive mechanical ventilation, for whom 1,217 daily assessments were applied at the bedside. The weighted total score of the prediction model showed the highest discriminatory power for the spontaneous breathing test, with sensitivity and specificity indices for fitness failure of 89.7% or success of 84.6%. The cutoff point suggested by the checklist was 8, with a probability of extubation failure less than 5%. Failure increased progressively with increasing score, with a maximum probability of predicting extubation failure of 85%. CONCLUSION: The extubation failure rate with the use of this model was within what is acceptable in the literature. The daily checklist model for the spontaneous breathing test was able to identify predictive variables of failure in the extubation process in pediatric patients.

Hematopoietic cell transplantation for telomere biology diseases: A retrospective single-center cohort study.

BACKGROUND: Telomere biology diseases (TBD) result from defective telomere maintenance, leading to bone marrow failure. The only curative treatment for aplastic anemia related to TBD is a hematopoietic cell transplant (HCT). Although reduced-intensity conditioning (RIC) regimens decrease transplant-related mortality, non-hematological phenotypes represent a major challenge and are associated with poor long-term follow-up outcomes. OBJECTIVE: To describe the outcome of TBD patients transplanted for marrow failure. STUDY DESIGN: This is a retrospective, single-center study describing the outcomes of 32 consecutive transplants on 29 patients between 1993 and 2019. RESULTS: The median age at transplantation was 14 years (range, 3-30 years). Most patients received a RIC regimen (n = 28) and bone marrow (BM) from an unrelated donor (n = 16). Four patients received a haploidentical transplant. Chimerism was available for 27 patients with a median time to neutrophil recovery of 20 days (13-36 days). Primary graft failure occurred in one patient, whereas second graft failure occurred in two. Acute GVHD grade II-IV and moderate to severe chronic GVHD occurred in 22% of patients at risk. Fourteen patients were alive after HCT at the last follow-up (median, 6 years; 1.4-19 years). The 5-year overall survival was better after matched sibling donor (MSD) transplantation compared to other hematopoietic stem cell sources (88.9% vs. 47.7%; p = .05; CI = 95%). Overall, 15 patients died after HCT, most of them (n = 11) after the first year of transplant, due to non-hematological disease progression or complication of chronic GVHD. CONCLUSIONS: Hematopoietic cell transplantation is a potentially curative treatment option for TBD, nonetheless the poor outcome reflects the progression of non-hematologic disease manifestations, which should be considered when transplantation is indicated.

Pediatric unplanned extubation risk score: A predictive model for risk assessment.

BACKGROUND: Unplanned extubation is one of the most common preventable adverse events associated with invasive mechanical ventilation. OBJECTIVE: This research study aimed to develop a predictive model to identify the risk of unplanned extubation in a pediatric intensive care unit (PICU). METHODS: This single-center, observational study was conducted at the PICU of the Hospital de Clínicas. Patients were included based on the following criteria: aged between 28 days and 14 years, intubated, and using invasive mechanical ventilation. RESULTS: Over 2 years, 2,153 observations were made using the Pediatric Unplanned Extubation Risk Score predictive model. Unplanned extubation occurred in 73 of 2,153 observations. A total of 286 children participated in the application of the Risk Score. This predictive model was created to categorize the following significant risk factors: 1) inadequate placement and fixation of the endotracheal tube (odds ratio 2.00 [95%CI,1.16-3.36]), 2) Insufficient level of sedation (odds ratio 3.00 [95%CI,1.57-4.37]), 3) age ≤ 12 months (odds ratio 1.27 [95%CI,1.14-1.41]), 4) presence of airway hypersecretion (odds ratio 11.00 [95%CI,2,58-45.26]) inadequate family orientation and/or nurse to patient ratio (odds ratio 5.00 [95%CI,2.64-7.99]), and 6) weaning period from mechanical ventilation (odds ratio 3.00 [95%CI,1.67-4.79]) and 5 risk enhancement factors. CONCLUSIONS: The scoring system demonstrated effective sensitivity for estimating the risk of UE with the observation of six aspects, which overlap as an isolated risk factor or are associated with a risk enhancement factors.

Fitness checklist model for spontaneous breathing tests in pediatrics / Modelo de checklist de, aptidão para teste de respiração espontânea em pediatria

ABSTRACT Objective: To evaluate whether a model of a daily fitness checklist for spontaneous breathing tests is able to identify predictive variables of extubation failure in pediatric patients admitted to a Brazilian intensive care unit. Methods: This was a single-center, cross-sectional study with prospective data collection. The checklist model comprised 20 items and was applied to assess the ability to perform spontaneous breathing tests. Results: The sample consisted of 126 pediatric patients (85 males (67.5%)) on invasive mechanical ventilation, for whom 1,217 daily assessments were applied at the bedside. The weighted total score of the prediction model showed the highest discriminatory power for the spontaneous breathing test, with sensitivity and specificity indices for fitness failure of 89.7% or success of 84.6%. The cutoff point suggested by the checklist was 8, with a probability of extubation failure less than 5%. Failure increased progressively with increasing score, with a maximum probability of predicting extubation failure of 85%. Conclusion: The extubation failure rate with the use of this model was within what is acceptable in the literature. The daily checklist model for the spontaneous breathing test was able to identify predictive variables of failure in the extubation process in pediatric patients.

RESUMO Objetivo: Avaliar se um modelo de checklist diário de aptidão para o teste de respiração espontânea é capaz de identificar variáveis preditivas de falha no processo de extubação em pacientes pediátricos internados em uma unidade de terapia intensiva brasileira. Métodos: Estudo unicêntricotransversal, com coleta prospectiva de dados. O modelo de checklist foi elaborado com 20 itens e aplicado para avaliação de aptidão para o teste de respiração espontânea. Resultados: A amostra foi composta de 126 pacientes pediátricos em ventilação mecânica invasiva, 85 do sexo masculino (67,5%), para os quais foram aplicadas 1.217 avaliações diárias à beira do leito. A pontuação total ponderada do modelo de predição apresentou o maior poder de discriminação para a realização do teste de respiração espontânea, com índices de sensibilidade e especificidade para a falha de aptidão de 89,7% ou sucesso de 84,6%. O ponto de corte sugerido pelo checklist foi 8, com probabilidade de falha de extubação inferior a 5%. Observou-se que a falha aumentou progressivamente com o aumento da pontuação obtida, com probabilidade máxima de predição de falha de extubação de 85%. Conclusão: A taxa de falha de extubação com a utilização desse modelo ficou dentro do que é aceitável na literatura. O modelo de checklist diário para aptidão do teste de respiração espontânea foi capaz de identificar variáveis preditivas de falha no processo de extubação em pacientes pediátricos.

Mental Health and Emotional Disorders During the COVID-19 Pandemics: Prevalence and Extent in PICU Staff.

OBJECTIVES: To assess the prevalence of burnout, anxiety and depression symptoms, and posttraumatic stress disorder (PTSD) in PICU workers in Brazil during the first peak of the COVID-19 pandemic. To compare the results of subgroups stratified by age, gender, professional category, health system, and previous mental health disorders. DESIGN: Multicenter, cross-sectional study using an electronic survey. SETTING: Twenty-nine public and private Brazilian PICUs. SUBJECTS: Multidisciplinary PICU workers. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Self-reported questionnaires were used to measure burnout (Maslach Burnout Inventory), anxiety and depression (Hospital Anxiety and Depression Scale), and PTSD (Posttraumatic Stress Disorder Checklist for Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition [PCL-5]) in 1,084 respondents. Subjects were mainly young (37.1 ± 8.4 yr old) and females (85%), with a median workload of 50 hours per week. The prevalence of anxiety and depression was 33% and 19%, respectively, whereas PTSD was 13%. The overall median burnout scores were high in the emotional exhaustion and personal accomplishment dimensions (16 [interquartile range (IQR), 8-24] and 40 [IQR, 33-44], respectively) whereas low in the depersonalization one (2 [IQR, 0-5]), suggesting a profile of overextended professionals, with a burnout prevalence of 24%. Professionals reporting prior mental health disorders had higher prevalence of burnout (30% vs 22%; p = 0.02), anxiety (51% vs 29%; p < 0.001), and depression symptoms (32.5% vs 15%; p < 0.001), with superior PCL-5 scores for PTSD ( p < 0.001). Public hospital workers presented more burnout (29% vs 18.6%, p < 0.001) and more PTSD levels (14.8% vs 10%, p = 0.03). Younger professionals were also more burned out ( p < 0.05 in all three dimensions). CONCLUSIONS: The prevalence of mental health disorders in Brazilian PICU workers during the first 2020 peak of COVID-19 was as high as those described in adult ICU workers. Some subgroups, particularly those reporting previous mental disorders and younger professionals, should receive special attention to prevent future crises.

Kidney complications in 107 Fanconi anemia patients submitted to hematopoietic cell transplantation.

Fanconi anemia (FA) is a rare disease characterized by progressive bone marrow failure, cancer predisposition, and multiple systemic malformations, including congenital abnormalities of the kidney and urinary tract (CAKUT). Hematopoietic cell transplantation (HCT), the only potentially curative treatment for the hematological complications of FA, may precipitate acute kidney injury (AKI) and hypertension. We retrospectively investigated 107 FA patients who underwent HCT between 2009 and 2017. We investigated the incidence and risk factors of AKI within 100 days after HCT in a cohort of FA patients, and kidney function and hypertension over 2-year follow-up.The incidence of AKI (mainly stage I) was 18.7%. Patients aged ≥ 11 years at transplantation showed a higher risk of AKI (OR 3.53). The eGFR was 60-90 mL/min/1.73 m2 in 53 (49.5%), 55 (51.4%), 50 (50.5%), 50 (51%), and 46 (59.7%) patients before HCT, at 100 days, 6 months, 1 year, and 2 years. Within the first 100 days after HCT, hypertension was observed in 72% of the patients and was associated with cyclosporine therapy. Most (62.3%) patients had stage 2 hypertension. CAKUT was observed in 33.7% of the patients and was associated with both hypertension (86%) and diminished kidney function but not with AKI.Conlusion: Although AKI, a commonly known HCT complication, was mild in this study, the prevalence of chronic kidney disease (CKD), as well as the high incidence of hypertension, specially associated with CAKUT point out the importance of kidney care in short and long-term follow up of FA patients. What is Known: • Fanconi anemia (FA) is the most frequent inherited bone marrow failure in children, and 30% of cases have congenital anomalies of kidney (CAKUT). • Acute kidney injury and hypertension after hematopoietic cell transplantation (HCT) may impact the outcomes.. What is New: • Despite the presence of CAKUT and stage 2 CKD in 33.7% and 50% of the patients, respectively, AKI was mild and transitory after HCT in FA patients. • CAKUT in FA patients was associated with lower kidney function and hypertension after HCT.

High flow nasal cannula in asthmatic children with suspected COVID-19 / Cânula nasal de alto fluxo em crianças asmáticas com suspeita de COVID-19

Abstract Introduction: The use of a high-flow nasal cannula as an alternative treatment for acute respiratory failure can reduce the need for invasive mechanical ventilation and the duration of hospital stays. Objective: The present study aimed to describe the use of a high-flow nasal cannula in pediatric asthmatic patients with acute respiratory failure and suspected COVID-19. Methods: To carry out this research, data were collected from medical records, including three patients with asthma diagnoses. The variables studied were: personal data (name, age in months, sex, weight, and color), clinical data (physical examination, PRAM score, respiratory rate, heart rate, and peripheral oxygen saturation), diagnosis, history of the current disease, chest, and laboratory radiography (arterial blood gases and reverse-transcriptase polymerase chain reaction). Clinical data were compared before and after using a high-flow nasal cannula. Results: After the application of the therapy, a gradual improvement in heart, respiratory rate, PaO2/FiO2 ratio, and the Pediatric Respiratory Assessment Measure score was observed. Conclusion: The simple and quick use of a high-flow nasal cannula in pediatric patients with asthma can be safe and efficient in improving their respiratory condition and reducing the need for intubation.

Resumo Introdução: A utilização da cânula nasal de alto fluxo como alternativa de tratamento para a insuficiência respiratória aguda pode diminuir a necessidade de utilização de ventilação mecânica invasiva e reduzir os dias de internamento. Objetivo: Descrever a utilização da cânula nasal de alto fluxo em pacientes pediátricos asmáticos com insuficiência respiratória aguda e suspeita de COVID-19. Métodos: Para a realização dessa pesquisa foram coletados dados de prontuários, sendo três pacientes com diagnóstico de asma incluídos. As variáveis estudadas foram: dados pessoais (nome, idade em meses, sexo, peso e cor) e clínicos (exame físico, PRAM Escore, frequência respiratória, frequência cardíaca, e saturação periférica de oxigênio), diagnóstico, história da moléstia atual, radiografia de tórax e exames laboratoriais (gasometria arterial e Reverse-Transcriptase Polymerase Chain Reaction). Foram comparados dados clínicos antes e após a utilização da cânula nasal de alto fluxo. Resultados: Após a aplicação da terapia foi possível observar melhora gradativa da frequência cardíaca e respiratória, relação PaO2/FiO2 e do escore Pediatric Respiratory Assessment Measure. Conclusão: A utilização simples e rápida da cânula nasal de alto fluxo em pacientes pediátricos com asma pode ser segura e eficiente para melhora do quadro respiratório, diminuindo a necessidade de intubação.

Outcomes after Haploidentical Stem Cell Transplantation with Post-Transplantation Cyclophosphamide in Patients with Primary Immunodeficiency Diseases.

Allogeneic hematopoietic stem cell transplantation (HCT) can cure primary immunodeficiency diseases (PID). When a HLA-matched donor is not available, a haploidentical family donor may be considered. The use of T cell-replete haploidentical HCT with post-transplantation cyclophosphamide (haplo-PTCy) in children with PID has been reported in few case series. A donor is usually readily available, and haplo-PTCy can be used in urgent cases. We studied the outcomes of 73 patients with PID who underwent haplo-PTCy, including 55 patients who did so as a first transplantation and 18 who did so as a salvage transplantation after graft failure of previous HCT. The median patient age was 1.6 years. Most of the children were male (n = 54) and had active infection at the time of transplantation (n = 50); 10 children had severe organ damage. The diagnosis was severe combined immunodeficiency (SCID) in 34 patients and non-SCID in 39 (Wiskott-Aldrich syndrome; n = 14; chronic granulomatous disease, n = 10; other PID, n = 15). The median duration of follow-up of survivors was 2 years. The cumulative incidence of neutrophil recovery was 88% in the SCID group and 84% in non-SCID group and was 81% for first transplantations and 83% after a salvage graft. At 100 days, the cumulative incidence of acute GVHD grade II-IV and III-IV was 33% and 14%, respectively. The majority of patients reached 200/µL CD4+ and 1000/µL CD3+ cell counts between 3 and 6 months. The estimated 2-year overall survival was 66%; it was 64% for SCID patients and 65% for non-SCID patients and 63% for first HCT and 77% for salvage transplantations. Twenty-five patients died, most of them due to infection early after transplantation (before 100 days). In conclusion, haplo-PTCy is a feasible procedure, can cure two-thirds of children with PID, and can be used as rescue treatment for previous graft failure. © 2020 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc.

The challenge of long-term follow-up of survivors of childhood acute leukemia after hematopoietic stem cell transplantation in resource-limited countries: A single-center report from Brazil.

With the number of long-term HSCT survivors steadily increasing, attention needs to be focused on the late complications and quality of life. We therefore analyzed the outcome of 101 pediatric patients (<18 years old at the time of HSCT) transplanted for acute leukemia between 1981 and 2015 at Complexo Hospital de Clínicas, Federal University of Paraná, Brazil, and who survived at least two years after HSCT. The median follow-up was 5.9 years (2.0-29.0); median age at follow-up was 17.5 years (2.98-39.0). The 5-year cumulative incidence of relapse was 27.5% (95% CI 18.6%-36.4%). Two-year cumulative incidence of chronic GVHD was 21.8% (95% CI 13.7%-29.8%). Of the 101 patients, 72 patients (71.3%) presented with late effects. Those surviving longer after HSCT experienced more complications. Patients who received TBI-based regimen developed more late effects (P = .013) and more endocrinological complications (P = .024). Endocrinological complications were the most common late sequelae found in this study. For childhood survivors, quality of life was not influenced by age (at HSCT or at last visit), time from HSCT, gender, donor, or GVHD. For survivors that no longer were children, only age at last visit impacted financial domain measures, irrespective of gender, donor, or GVHD. The current study confirms the high burden late complications after pediatric HSCT have on the survivors and underlines the importance of extended follow-up.

DIABETIC KETOACIDOSIS AS THE INITIAL PRESENTATION OF TYPE 1 DIABETES IN CHILDREN AND ADOLESCENTS: EPIDEMIOLOGICAL STUDY IN SOUTHERN BRAZIL.

OBJECTIVE: To analyze the variables associated with the presence of diabetic ketoacidosis in type 1 diabetes mellitus (T1DM) diagnosis and its impact on the progression of the disease. METHODS: We reviewed the records of 274 children and adolescents under 15 years, followed in a Pediatric Endocrinology clinic of a university hospital in Curitiba-PR. They had their first appointment between January 2005 and April 2015. RESULTS: Most patients received their T1DM diagnosis during a diabetic ketoacidosis episode. The associated factors were: lower age and greater number of visits to a physician's office prior to diagnosis; diabetic ketoacidosis was less frequent in patients who had siblings with T1DM and those diagnosed at the first appointment. Nausea and vomiting, abdominal pain, tachydyspnea, and altered level of consciousness were more common in the diabetic ketoacidosis group. There was no association with socioeconomic status, duration of symptoms before diagnosis, and length of the honeymoon period. CONCLUSIONS: Prospective studies are necessary to better define the impact of these factors on diagnosis and disease control. Campaigns to raise awareness among health professionals and the general population are essential to promote early diagnosis and proper treatment of diabetes mellitus in children and adolescents.

Diabetic ketoacidosis as the initial presentation of type 1 diabetes in children and adolescents: epidemiological study in southern brazil / Cetoacidose diabética como apresentação inicial de diabetes tipo 1 em crianças e adolescentes: estudo epidemiológico no sul do brasil

ABSTRACT Objective: To analyze the variables associated with the presence of diabetic ketoacidosis in type 1 diabetes mellitus (T1DM) diagnosis and its impact on the progression of the disease. Methods: We reviewed the records of 274 children and adolescents under 15 years, followed in a Pediatric Endocrinology clinic of a university hospital in Curitiba-PR. They had their first appointment between January 2005 and April 2015. Results: Most patients received their T1DM diagnosis during a diabetic ketoacidosis episode. The associated factors were: lower age and greater number of visits to a physician's office prior to diagnosis; diabetic ketoacidosis was less frequent in patients who had siblings with T1DM and those diagnosed at the first appointment. Nausea and vomiting, abdominal pain, tachydyspnea, and altered level of consciousness were more common in the diabetic ketoacidosis group. There was no association with socioeconomic status, duration of symptoms before diagnosis, and length of the honeymoon period. Conclusions: Prospective studies are necessary to better define the impact of these factors on diagnosis and disease control. Campaigns to raise awareness among health professionals and the general population are essential to promote early diagnosis and proper treatment of diabetes mellitus in children and adolescents.

RESUMO Objetivo: Avaliar as variáveis associadas ao diagnóstico de diabetes melito tipo 1 (DM1) na vigência de cetoacidose diabética e seu impacto na evolução da doença. Métodos: Foram avaliadas 274 crianças e adolescentes com idade até 15 anos acompanhados em um ambulatório de endocrinologia pediátrica de um hospital universitário de Curitiba, Paraná, cuja primeira consulta ocorreu entre janeiro de 2005 e abril de 2015. Resultados: A maioria dos pacientes teve diagnóstico de DM1 na vigência de cetoacidose diabética. Os fatores associados foram: menor idade e maior número de consultas prévias ao diagnóstico; a cetoacidose diabética foi menos frequente quando havia um irmão com DM1 e quando o diagnóstico foi feito na primeira consulta médica. Náuseas ou vômitos, dor abdominal, taquidispneia e alteração do nível de consciência foram mais frequentes no grupo com cetoacidose diabética ao diagnóstico. Não se observou associação com nível socioeconômico, tempo de sintomas antes do diagnóstico e duração do período de lua de mel. Conclusões: São necessários estudos prospectivos para definir melhor o impacto desses fatores no diagnóstico e no controle da doença. Campanhas de conscientização dos profissionais de saúde e da população são necessárias para que haja diagnóstico precoce e tratamento adequado do diabetes melito em crianças e adolescentes.

Complicações relacionadas ao uso de soluções hipotônicas e isotônicas / Complications related to the use of hypotonic and isotonic solutions

OBJETIVO: Comparar a incidência de hiponatremia e complicações relacionadas nas crianças internadas na UTI Pediátrica tratadas com solução isotônica e hipotônica. MÉTODOS: Estudo prospectivo, randomizado, tipo caso-controle. Grupo controle com manutenção de fluido hipotônico e grupo estudo com fluido isotônico. Incluído crianças admitidas na UTI Pediátrica do Hospital de Clínicas de Curitiba. Excluídos diabetes mellitus, diabetes insípidos, hepatopatia crônica e menos de quatro horas de hidratação. RESULTADOS: Assim como a osmolaridade, apesar de não observarmos significância estatística, o sódio sérico do grupo hipotônico teve uma queda principalmente nas primeiras 12 horas enquanto o sódio sérico do grupo isotônico teve aumento progressivo nas primeira 48 horas. Não houve hipernatremia nos pacientes que hidrataram com solução isotônica. CONCLUSÃO: Observado uma tendência a hiponatremia no grupo controle de solução hipotônica. Complicações como alterações neurológicas ocorreu apenas no grupo com solução hipotônica após 12 horas de hidratação, porém sem significância estatística

OBJECTIVE: To compare the incidence of hyponatremia and related complications in children hospitalized in the Pediatric ICU treated with isotonic and hypotonic solution. METHODS: Prospective, randomized, case-control study. Control group with maintenance of hypotonic fluid and study group with isotonic fluid. Including children admitted to the Pediatric ICU of the Hospital de Clínicas de Curitiba. Excluded diabetes mellitus, diabetes insipidus, chronic liver disease and less than four hours of hydration. RESULTS: Like osmolarity, although we did not observe statistical significance, the serum sodium of the hypotonic group had a decrease mainly in the first 12 hours while serum sodium from the isotonic group had a progressive increase in the first 48 hours. There was no hypernatremia in the patients who hydrated with isotonic solution. CONCLUSION: Hyponatremia was observed in the hypotonic solution control group. Complications such as neurological changes occurred only in the group with hypotonic solution after 12 hours of hydration, but without statistical significance

Transplantation of Hematopoietic Stem Cells for Primary Immunodeficiencies in Brazil: Challenges in Treating Rare Diseases in Developing Countries.

The results of hematopoietic stem cell transplant (HSCT) for primary immunodeficiency diseases (PID) have been improving over time. Unfortunately, developing countries do not experience the same results. This first report of Brazilian experience of HSCT for PID describes the development and results in the field. We included data from transplants in 221 patients, performed at 11 centers which participated in the Brazilian collaborative group, from July 1990 to December 2015. The majority of transplants were concentrated in one center (n = 123). The median age at HSCT was 22 months, and the most common diseases were severe combined immunodeficiency (SCID) (n = 67) and Wiskott-Aldrich syndrome (WAS) (n = 67). Only 15 patients received unconditioned transplants. Cumulative incidence of GVHD grades II to IV was 23%, and GVHD grades III to IV was 10%. The 5-year overall survival was 71.6%. WAS patients had better survival compared to other diseases. Most deaths (n = 53) occurred in the first year after transplantation mainly due to infection (55%) and GVHD (13%). Although transplant for PID patients in Brazil has evolved since its beginning, we still face some challenges like delayed diagnosis and referral, severe infections before transplant, a limited number of transplant centers with expertise, and resources for more advanced techniques. Measures like newborn screening for SCID may hasten the diagnosis and ameliorate patients' conditions at the moment of transplant.

Haploidentical Bone Marrow Transplantation with Post-Transplant Cyclophosphamide for Children and Adolescents with Fanconi Anemia.

We describe haploidentical bone marrow transplantation with post-transplant cyclophosphamide (PT-CY) for 30 patients with Fanconi anemia (FA). Twenty-six patients were transplanted upfront, and the preparatory regimens included fludarabine 150 mg/m2 + total body irradiation 200 to 300 cGy ± CY 10 mg/kg without (n = 12) or with rabbit antithymocyte globulin (r-ATG) 4 to 5 mg/kg (n = 14). Four patients were rescued after primary or secondary graft failure after related or unrelated donor transplantation with the above regimen with (n = 2) or without r-ATG (n = 2). PT-CY at 25 mg/kg/day (total dose, 50 mg/kg) followed by cyclosporine and mycophenolate mofetil was given to all patients. All patients engrafted in the subgroup of patients who did not receive r-ATG (n = 14), but their transplant course was complicated by high rates of acute and chronic graft-versus-host disease (GVHD), and only 8 patients are alive. In the subgroup that received r-ATG (n = 16), 14 patients had sustained engraftment, severe GVHD rates were lower, and 13 patients are alive. Hemorrhagic cystitis occurred in 50% of patients, whereas cytomegalovirus reactivation occurred in 75%. One-year overall survival for the entire cohort was 73% (95% CI, 64% to 81%), and all surviving patients achieved full donor chimerism. In conclusion, haploidentical donor transplantation with PT-CY is a suitable option for FA patients without a matched related or unrelated donor.

Long-term Survival, Organ Function, and Malignancy after Hematopoietic Stem Cell Transplantation for Fanconi Anemia.

We report on long-term survival in 157 patients with Fanconi anemia (FA) who survived 2 years or longer after their first transplantation with a median follow-up of 9 years. Marrow failure (80%) was the most common indication for transplantation. There were 20 deaths beyond 2 years after transplantation, with 12 of the deaths occurring beyond 5 years after transplantation. Donor chimerism was available for 149 patients: 112 (76%) reported > 95% chimerism, 27 (18%) reported 90% to 95% chimerism, and 8 (5%) reported 20% to 89% donor chimerism. Two patients have < 20% donor chimerism. The 10- and 15-year probabilities of survival were 90% and 79%, respectively. Results of multivariate analysis showed higher mortality risks for transplantations before 2003 (hazard ratio [HR], 7.87; P = .001), chronic graft-versus-host disease (GVHD) (HR, 3.80; P = .004) and squamous cell carcinoma after transplantation (HR, 38.17; P < .0001). The predominant cause of late mortality was squamous cell carcinoma, with an incidence of 8% and 14% at 10 and 15 years after transplantation, respectively, and was more likely to occur in those with chronic GVHD. Other causes of late mortality included chronic GVHD, infection, graft failure, other cancers, and hemorrhage. Although most patients are disease free and functional long term, our data support aggressive surveillance for long periods to identify those at risk for late mortality.

Long-term outcome and lineage-specific chimerism in 194 patients with Wiskott-Aldrich syndrome treated by hematopoietic cell transplantation in the period 1980-2009: an international collaborative study.

In this retrospective collaborative study, we have analyzed long-term outcome and donor cell engraftment in 194 patients with Wiskott-Aldrich syndrome (WAS) who have been treated by hematopoietic cell transplantation (HCT) in the period 1980- 2009. Overall survival was 84.0% and was even higher (89.1% 5-year survival) for those who received HCT since the year 2000, reflecting recent improvement of outcome after transplantation from mismatched family donors and for patients who received HCT from an unrelated donor at older than 5 years. Patients who went to transplantation in better clinical conditions had a lower rate of post-HCT complications. Retrospective analysis of lineage-specific donor cell engraftment showed that stable full donor chimerism was attained by 72.3% of the patients who survived for at least 1 year after HCT. Mixed chimerism was associated with an increased risk of incomplete reconstitution of lymphocyte count and post-HCT autoimmunity, and myeloid donor cell chimerism < 50% was associated with persistent thrombocytopenia. These observations indicate continuous improvement of outcome after HCT for WAS and may have important implications for the development of novel protocols aiming to obtain full correction of the disease and reduce post-HCT complications.

Transplante de células-tronco hematopoéticas em crianças e adolescentes com leucemia aguda: experiência de duas instituições brasileiras / Hematopoietic stem cell transplantation in children and adolescents with acute leukemia: experience of two Brazilian institutions

O transplante de células-tronco hematopoéticas (TCTH) é o tratamento de escolha para leucemias agudas de alto risco. Apesar da melhora na sobrevida destes pacientes, a recidiva continua sendo a maior causa de óbito pós-transplante de células-tronco hematopoéticas. O objetivo deste trabalho foi analisar os resultados dos transplantes realizados em crianças com leucemia aguda em duas instituições brasileiras. Realizou-se estudo retrospectivo de 208 pacientes transplantados entre 1990-2007. Mediana de idade: 9 anos; 119 pacientes com leucemia linfoide aguda (LLA) e 89 com leucemia mieloide aguda (LMA). Doença precoce: CR1 e CR2. ... 14/195 pacientes tiveram falha primária de pega (8 por cento). Não houve diferença na sobrevida global e sobrevida livre de recaída entre pacientes com leucemia linfoide aguda e leucemia mieloide aguda, entre transplantes aparentados e não aparentados, tampouco entre as fontes de células utilizadas. O desenvolvimento da doença do enxerto contra hospedeiro (DECH) aguda ou crônica também não influenciou a sobrevida global e sobrevida livre de recaída. Pacientes com leucemia linfoide aguda condicionados com irradiação corporal total (TBI) apresentaram melhor sobrevida global e sobrevida livre de recaída (p<0,001). Cento e dezoito pacientes morreram entre 1-1.654 dias pós-transplante de células-tronco hematopoéticas (M:160). Mortalidade relacionada a transplante (MRT) (dia+100): 16 por cento. Incidência cumulativa de recaída: 40 por cento (3 anos). Pacientes com doença avançada tiveram menor sobrevida global e sobrevida livre de recaída (três anos)(p<0,001). Na análise multivariada, o status da doença foi o principal fator associado ao aumento da sobrevida global e sobrevida livre de recaída. Nossos resultados mostram que é possível se atingir uma boa sobrevida para pacientes com doença precoce e também mostram a baixa eficácia naqueles com doença avançada.

Hematopoietic Stem Cell transplantation (HSCT) is the treatment of choice for patients with high-risk leukemia. In spite of this, relapse remains a major cause of death of these patients. Our objective was to analyze the outcomes of patients with acute leukemia submitted to hematopoietic stem cell transplantation in two Brazilian institutions... There were no differences in the overall survival and event free survival between patients with acute lymphocytic leukemia and acute myeloid leukemia, between sources of cells used or between those who developed acute or chronic graft-versus-host disease (GVHD). When comparing transplants from related and unrelated donors, there was no difference in the overall survival. Patients with acute lymphocytic leukemia receiving the total body irradiation (TBI) conditioning regimen had better overall survival and event free survival (p<0.001). One hundred and eighteen patients died between 0 and 1654 days after hematopoietic stem cell transplantation (M: 160 days). Transplantation-related-mortality (TRM) at D+100 was 16 percent and cumulative incidence of relapse was 40 percent (3 years). Patients with advanced disease had lower 3-year overall survival and event free survival (p<0.001). Multivariate analysis showed that disease status was the most significant factor associated with higher event free survival and overall survival . Our results show that children and adolescents transplanted with early disease can achieve considerable overall survival and also highlights the inefficacy of hematopoietic stem cell transplantation for patients with advanced disease.

A manobra de recrutamento alveolar em crianças submetidas à ventilação mecânica em unidade de terapia intensiva pediátrica / Alveolar recruitment maneuver in mechanic ventilation pediatric intensive care unit children

Recentes mudanças foram introduzidas na forma de ventilar crianças com doenças que determinam o quadro de insuficiência respiratória aguda hipoxêmica. Há evidências que estratégias ventilatórias menos agressivas, melhoram a sobrevida de pacientes com grave lesão pulmonar. Estudos experimentais evidenciaram relação entre modalidades ventilatórias inapropriadas e retardo na melhora e até mesmo piora da lesão pulmonar aguda. A partir desta concepção, surge uma estratégia ventilatória protetora, combinada à manobra de recrutamento alveolar. Acredita-se, que esta associação na prática clínica, determina importante redução da morbidade e mortalidade, bem como, prevenção das lesões induzidas pela ventilação mecânica. Sua indicação relaciona-se com quadros de lesão pulmonar aguda, geralmente decorrente de pneumonia ou sepse, que cursam com grave hipoxemia. Suas principais contra-indicações são instabilidade hemodinâmica, presença de pneumotórax e hipertensão intracraniana. Estudos experimentais demonstraram efeitos benéficos da manobra sobre a oxigenação e colapso alveolar. Estudos em adultos demonstraram melhora da função pulmonar e reversão da hipoxemia. Em crianças, a manobra demonstrou significativa redução da fração inspirada de oxigênio e do colapso alveolar, menor dependência ao oxigênio, melhora da complacência pulmonar e menor índice de displasia broncopulmonar. Porém, os estudos em pediatria são limitados. Faz-se necessária maior investigação sobre o tema e evidências de sua aplicação clínica. Foi realizada revisão da literatura, com pesquisa de livros-texto e nas bases de dados da MEDLINE, Pubmed, Cochrane library, SciELO e Ovid, no período de 1998 até 2009, em português e inglês. Foram incluídas publicações acerca da manobra de recrutamento alveolar em adultos e crianças, artigos de revisão, estudos experimentais e ensaios clínicos utilizando as palavras-chave: estratégia ventilatória protetora, manobra de recrutamento alveolar, pediatria ...

Recent changes were introduced in acute hypoxemic respiratory failure children ventilation methods. There are evidences that less aggressive ventilation strategies can improve severe pulmonary injury survival. Experimental trials evidenced a relationship between inappropriate ventilatory measures and delayed acute pulmonary injury improvement, or even worsening. From this, a protective ventilatory measure arises in combination with alveolar recruitment maneuver. This association is believed in clinical practice to determine importantly reduced morbidity and mortality as well as reduced mechanic ventilation-induced injuries. It is indicated for acute lung injury patients, generally from pneumonia or sepsis, with severe hypoxemia. Its main contraindications are homodynamic instability, pneumothorax and intracranial hypertension. Experimental trials showed beneficial maneuver effects on both oxygenation and alveolar collapse. Adult studies showed improved pulmonary function with hypoxemia reversion. In children, the maneuver lead to significant inspired oxygen fraction and alveolar collapse reductions, less oxygen dependency, improved pulmonary complacency, and reduced bronchopulmonary dysplasia. However, studies in children are limited. Additional investigation is warranted on this matter, and its clinical application evidence. A literature review was conducted based on textbooks and MEDLINE, Pubmed, Cochrane library, SciELO, and Ovid databases, from 1998 to 2009, both in Portuguese and English. Publications on alveolar recruitment maneuver both in adults and children, review articles, experimental and clinical trials were included using the key words: protective ventilatory strategy, alveolar recruitment maneuver, pediatrics and mechanic ventilation.