RESUMO
There is limited information regarding the long-term outcomes of hematopoietic stem cell transplantation (HSCT) for mucopolysaccharidosis II (MPS II). In this study, clinical, biochemical, and radiologic findings were assessed in patients who underwent HSCT and/or enzyme replacement therapy (ERT). Demographic data for 146 HSCT patients were collected from 27 new cases and 119 published cases and were compared with 51 ERT and 15 untreated cases. Glycosaminoglycan (GAG) levels were analyzed by liquid chromatography tandem mass spectrometry in blood samples from HSCT, ERT, and untreated patients as well as age-matched controls. Long-term magnetic resonance imaging (MRI) findings were investigated in 13 treated patients (6 ERT and 7 HSCT). Mean age at HSCT was 5.5 years (range, 2 to 21.4 years) in new patients and 5.5 years (range, 10 months to 19.8 years) in published cases. None of the 27 new patients died as a direct result of the HSCT procedure. Graft-versus-host disease occurred in 8 (9%) out of 85 published cases, and 9 (8%) patients died from transplantation-associated complications. Most HSCT patients showed greater improvement in somatic features, joint movements, and activity of daily living than the ERT patients. GAG levels in blood were significantly reduced by ERT and levels were even lower after HSCT. HSCT patients showed either improvement or no progression of abnormal findings in brain MRI while abnormal findings became more extensive after ERT. HSCT seems to be more effective than ERT for MPS II in a wide range of disease manifestations and could be considered as a treatment option for this condition.
Assuntos
Terapia de Reposição de Enzimas/métodos , Transplante de Células-Tronco Hematopoéticas/métodos , Mucopolissacaridose II/terapia , Adolescente , Criança , Pré-Escolar , Glicosaminoglicanos/sangue , Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/mortalidade , Humanos , Imageamento por Ressonância Magnética , Adulto JovemRESUMO
OBJECTIVE: To evaluate differences between pediatricians and internists in the practice of and barriers to advance care planning (ACP) for adolescent patients with cancer. STUDY DESIGN: A self-reported questionnaire was administered to assess the practice of ACP, advance directives, and barriers to ACP for adolescent patients with cancer. All 3392 Japanese board-certified hematologists were surveyed, and 600 hematologists (227 pediatricians, 373 internists) who take care of adolescent patients with cancer with decision-making capacity were analyzed. RESULTS: If a patient's prognosis for survival was <3 months, pediatricians were significantly less likely to discuss ACP with their patients than internists, including discussions regarding the patient's medical condition (59% vs 70%), the patient's understanding of his/her medical condition (55% vs 66%), do not attempt resuscitation orders (17% vs 24%), and ventilator treatment if the patient's condition worsened (19% vs 25%). More than 75% of hematologists (both pediatricians and internists) discussed all ACP topics with patients' families. Similarly, with regard to advance directives, pediatricians were less likely than internists to discuss cardiopulmonary resuscitation (24% vs 47%) and the use of ventilators (31% vs 51%), vasopressors (24% vs 42%), and antibiotics (21% vs 31%) with their patients. Both pediatricians and internists discussed these issues more often with patients' families than with patients, especially cardiopulmonary resuscitation (98%) as well as the use of ventilators (98%) and vasopressors (91%). CONCLUSIONS: Pediatricians were less likely than internists to discuss ACP and advance directives with patients, and both pediatricians and internists tended to discuss ACP and advance directives more often with patients' families.
Assuntos
Planejamento Antecipado de Cuidados/organização & administração , Atitude do Pessoal de Saúde , Médicos Hospitalares , Neoplasias/terapia , Pediatras , Inquéritos e Questionários , Adolescente , Adulto , Tomada de Decisão Clínica , Feminino , Pesquisas sobre Atenção à Saúde , Humanos , Medicina Interna , Masculino , Medicina , Pessoa de Meia-Idade , Neoplasias/mortalidade , Avaliação de Resultados em Cuidados de Saúde , Padrões de Prática Médica , Medição de RiscoRESUMO
OBJECTIVE: To investigate the differences in toll-like receptor (TLR)-mediated immune responses between human neonates and adults, focusing on the cytokine profiles of monocytes, dendritic cells (DCs), and monocyte-derived DCs (MoDCs) in cord and adult blood. STUDY DESIGN: Purified monocytes, DCs, and MoDCs were stimulated with the following TLR ligands: lipopolysaccharide (TLR4), Pam3CSK4 (TLR1/2), flagellin (TLR5), zymosan (TLR2), polyinosinic:polycytidylic acid (TLR3), imiquimod (TLR7), and CpG (TLR9). Interleukin (IL)-8, IL-6, tumor necrosis factor, IL-1ß, and IL-10 concentrations were analyzed in culture supernatants. RESULTS: Compared with the effects in adult blood, lipopolysaccharide-, Pam3CSK4-, flagellin-, and polyinosinic:polycytidylic acid-stimulated inflammatory cytokine production in cord blood was generally weak in monocytes, comparable in DCs, and elevated in MoDCs. CpG- and imiquimod-stimulated cytokine production in DCs was comparable in cord blood and adult blood, but cytokine production was almost absent in monocytes and MoDCs in both cord blood and adult blood. In contrast, zymosan stimulation produced comparable inflammatory cytokine profiles in the monocytes, DCs, and MoDCs of cord blood and adult blood. CONCLUSION: The immaturity of TLR-mediated innate immunity in neonates depends on monocytes rather than on DCs. Our results indicate that zymosan-mediated TLR2 signaling may be useful for developing a neonatal vaccine adjuvant.
Assuntos
Citocinas/metabolismo , Células Dendríticas/imunologia , Sangue Fetal/citologia , Monócitos/imunologia , Zimosan/farmacologia , Adjuvantes Imunológicos/farmacologia , Adulto , Aminoquinolinas/farmacologia , Células Cultivadas , Flagelina/farmacologia , Citometria de Fluxo , Humanos , Imiquimode , Recém-Nascido , Lipopeptídeos/farmacologia , Lipopolissacarídeos/farmacologia , Oligodesoxirribonucleotídeos/farmacologia , Poli I-C/farmacologiaRESUMO
OBJECTIVE: To assess the safety and efficacy of tetrahydrobiopterin therapy with sapropterin to treat tetrahydrobiopterin (BH4)-responsive phenylalanine hydroxylase (PAH) deficiency in children aged <4 years compared with those aged ≥4 years. STUDY DESIGN: We analyzed a longitudinal follow-up study conducted in all patients with BH4-responsive PAH deficiency throughout Japan. At the end of 2011, 43 patients were receiving sapropterin, of whom 21 were aged <4 years at the initiation of treatment. The starting dose of sapropterin was ≥10 mg/kg/day in 11 of these 21 patients. The duration of follow-up was ≥4 years in 6 of those 11 patients; 3 of these 6 were followed for ≥10 years. Nine patients were receiving sapropterin monotherapy at the end of 2011. RESULTS: Serum phenylalanine level was maintained within the recommended optimal control range in all 21 patients who started sapropterin treatment before age 4 years. Only 1 nonserious adverse drug reaction occurred, an elevated alanine aminotransferase level in 1 patient. No significant abnormal behavior related to nerve disorders was reported. CONCLUSION: Sapropterin therapy initiated before age 4 years was effective in maintaining serum phenylalanine level within the favorable range and was safe in Japanese patients with BH4-responsive PAH deficiency.