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1.
J Rheumatol ; 2019 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-31043544

RESUMO

OBJECTIVE: Deficiency of adenosine deaminase 2 (DADA2) is an autosomal recessive autoinflammatory disorder associated with ADA2 mutations. We aimed to investigate the characteristics and ADA2 enzyme activities of DADA2 patients compared to non-DADA2 patients. METHODS: This is a descriptive study consisting of 24 DADA2 patients who admitted to the Adult and Pediatric Rheumatology, Pediatric Haematology, and Pediatric Immunology Departments. All ADA2 exons were screened by Sanger sequencing. Serum ADA2 enzyme activity was measured by modified spectrophotometric method. RESULTS: 24 DADA2 patients were included; 14 with polyarteritis nodosa(PAN)-like phenotype (Group 1); 9 with Diamond-Blackfan anemia(DBA)-like features and one with immunodeficiency (Group 2). 14 PAN-like DADA2 patients did not have the typical thrombocytosis seen in classical PAN. Inflammatory attacks were evident in only Group 1 patients. Serum ADA2 activity was low in all DADA2 patients except one who was tested after hematopoietic stem cell transplantation. There was no significant difference in ADA2 activities between PAN-like and DBA-like patients. In DADA2 patients with one ADA2 mutation, serum ADA2 activities were as low as the ones of homozygote DADA2 patients. ADA2 activities were normal in non-DADA2 patients. ADA2 mutations were affecting the dimerization domain in Group 1 patients and the catalytic domain in Group 2 patients. CONCLUSION: We suggest to assess ADA2 activity along with genetic analysis since there are patients with one ADA2 mutation and absent enzyme activity. Our data suggest a possible genotype-phenotype correlation where dimerization domain mutations are associated with PAN-like phenotype and catalytic domain mutations are associated with hematological manifestations.

2.
Pediatr Blood Cancer ; 66(5): e27636, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30706992

RESUMO

AIM: Since the beginning of the Syrian civil war, more than 3.5 million Syrians have been under temporary protection status in Turkey. Because beta-thalassemia (BT) is a prevalent disorder in the Mediterranean countries, we decided to estimate the prevalence of and make an overview of the demographic, socioeconomic, medical characteristics, and healthcare problems of refugee children with BT. PATIENTS: Eighteen Turkish Pediatric Hematology Oncology Centers (PHOC) with 318 refugee children from 235 families participated in the study. The mean age of the patients was 8.1 ± 4.8 years (0.5-21 years). The mean time after immigration to Turkey was 2.5 ± 1.5 years (range, 0.1-7 years). Seventy-two (22.6%) of them were born and diagnosed with BT in Turkey. On physical examination, 82 patients (26%) were underweight and 121 patients (38%) were stunted. The appearance of a thalassemic face was reported for 207 patients (65.1%). Hepatomegaly and splenomegaly were reported in 217 (68.2%) and 168 (52.8%) patients, respectively. The median ferritin level was 2508 ng/mL (range, 17-21 000 ng/mL) at the first admission, and 2841 ng/mL (range, 26-12 981 ng/mL) at the last visit after two years of follow-up in a PHOC (P > 0.05). The most frequently encountered mutation was IVSI-110 (G>A) (31%). Before immigration, only 177 patients (55.6%) reported the use of chelators; after immigration it increased to 268 (84.3%). CONCLUSION: Difficulties in communication, finding a competent translator capable in medical terminology, nonregular use of medications, and insensitivity to prenatal diagnosis were preliminary problems. The current extent of migration poses emerging socioeconomic and humanitarian challenges for refugee patients with BT.

3.
Hemoglobin ; 42(2): 113-116, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30200834

RESUMO

Peripheral neuropathy is one of the complications of ß-thalassemia (ß-thal) that has been investigated in limited reports. We aimed to detect the rate of peripheral neuropathy and risk factors for neuropathy development in patients with ß-thal. The study was performed in patients with ß-thal intermedia (ß-TI) or ß-thal major (ß-TM). Prospective electrophysiological studies were achieved via standard procedures. A total of 27 patients were enrolled in the study. Electrophysiological studies for both motor and sensory nerves were within normal range. In motor nerve studies, delayed peroneal nerve latency was found in patients with high ferritin levels, increased ulnar nerve amplitude was detected in patients ≥20 years old, and increased tibial nerve amplitude was seen in patients with low copper levels. We could not show peripheral neuropathy in our patients. Increased ferritin level, older age, and copper deficiency may cause mild changes in electrophysiological studies of motor nerves.

4.
Turk J Haematol ; 35(4): 229-259, 2018 11 13.
Artigo em Inglês | MEDLINE | ID: mdl-30040071

RESUMO

Objective: To examine granulocytic and non-granulocytic cells in children with severe congenital neutropenia (SCN) and their non-neutropenic parents. Materials and Methods: Fifteen patients with SCN and 21 non-neutropenic parents were evaluated for a) CD95, CD95 ligand, annexin V, propidium iodide, cell cycle, and lymphocyte subsets by flow cytometry; b) rapid cell senescence (of leukocytes) by senescence-associated ß-galactosidase stain; c) aggregation tests by aggregometer; d) in vitro bleeding time by PFA-100 instrument; e) mepacrine-labeled dense granule number of thrombocytes by fluorescence microscope; and f) hematomorphology by light and electron microscope. HAX1, ELANE, G6PC3, CSF3R, and JAGN1 mutations associated with SCN were studied in patients and several parents. Results: Significant increase in apoptosis and secondary necrosis in monocytes, lymphocytes, and granulocytes of the patients and parents was detected, irrespective of the mutation type. CD95 and CD95 ligand results implied that apoptosis was non-CD95-mediated. Leukocytes of 25%, 12.5%, and 0% of patients, parents, and controls showed rapid cell senescence. The cell cycle analysis testable in four cases showed G1 arrest and apoptosis in lymphocytes of three. The patients had HAX1 (n=6), ELANE (n=2), G6PC3 (n=2), and unidentified (n=5) mutations. The CD3, CD4, and NK lymphocytes were below normal levels in 16.6%, 8.3%, and 36.4% of the patients and in 0%, 0%, and 15.4% of the parents (controls: 0%, 0%, 5.6%). The thrombocytes aggregated at low rates, dense granule number/thrombocyte ratio was low, and in vitro bleeding time was prolonged in 37.5%-66.6% of patients and 33.3%-63.2% of parents (vs. 0% in controls). Under electron and/or light microscope, the neutrophils, monocytes, lymphocytes, and thrombocytes in the peripheral blood of both patients and parents were dysplastic and the bone marrow of patients revealed increased phagocytic activity, dysmegakaryopoiesis, and necrotic and apoptotic cells. Ultrastructurally, thrombocyte adhesion, aggregation, and release were inadequate. Conclusion: In cases of SCN, patients' pluripotent hematopoietic stem cells and their non-neutropenic parents are both affected irrespective of the genetic defect.

5.
Proc Natl Acad Sci U S A ; 115(20): 5241-5246, 2018 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-29712865

RESUMO

BRCA1 is essential for repair of DNA double-strand breaks by homologous recombination, and hence for survival. Complete loss of its function is lethal during early embryonic development. Patients who are compound heterozygous for BRCA1 truncating mutations and missense alleles that retain some DNA repair capacity may survive, albeit with very high risk of early onset breast or ovarian cancer and features of Fanconi anemia. However, a mechanism enabling survival of patients homozygous for BRCA1 truncating mutations has not been described. We studied two unrelated families in which four children presented with multiple congenital anomalies and severe chromosomal fragility. One child developed T cell acute lymphocytic leukemia (ALL), and a second child developed neuroblastoma. Each of the four children was homozygous for a nonsense mutation in BRCA1 exon 11. Homozygosity for the nonsense mutations was viable thanks to the presence of a naturally occurring alternative splice donor in BRCA1 exon 11 that lies 5' of the mutations. The mutations did not affect the alternative splice site, but transcription from it produced an in-frame BRCA1 message with deletion of 3,309 bp. The translated BRCA1 protein was only 40% of normal length, but with intact N- and C-terminal sequences. These patients extend the range of BRCA1-related phenotypes and illustrate how naturally occurring alternative splicing can enable survival, albeit with severe consequences, of otherwise lethal genotypes of an essential gene.


Assuntos
Processamento Alternativo , Proteína BRCA1/genética , Neoplasias da Mama/genética , Códon sem Sentido , Homozigoto , Neoplasias Ovarianas/genética , Adolescente , Adulto , Neoplasias da Mama/patologia , Criança , Pré-Escolar , Feminino , Humanos , Neoplasias Ovarianas/patologia , Linhagem
7.
Blood Adv ; 2(6): 586-596, 2018 03 27.
Artigo em Inglês | MEDLINE | ID: mdl-29540340

RESUMO

Heterozygous mutations in MECOM (MDS1 and EVI1 complex locus) have been reported to be causative of a rare association of congenital amegakaryocytic thrombocytopenia and radioulnar synostosis. Here we report on 12 patients with congenital hypomegakaryocytic thrombocytopenia caused by MECOM mutations (including 10 novel mutations). The mutations affected different functional domains of the EVI1 protein. The spectrum of phenotypes was much broader than initially reported for the first 3 patients; we found familial as well as sporadic cases, and the clinical spectrum ranged from isolated radioulnar synostosis with no or mild hematological involvement to severe bone marrow failure without obvious skeletal abnormality. The clinical picture included radioulnar synostosis, bone marrow failure, clinodactyly, cardiac and renal malformations, B-cell deficiency, and presenile hearing loss. No single clinical manifestation was detected in all patients affected by MECOM mutations. Radioulnar synostosis and B-cell deficiency were observed only in patients with mutations affecting a short region in the C-terminal zinc finger domain of EVI1. We propose the term MECOM-associated syndrome for this heterogeneous hereditary disease and inclusion of MECOM sequencing in the diagnostic workup of congenital bone marrow failure.

8.
Am J Hematol ; 93(5): 672-682, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29396846

RESUMO

Mutations in more than 70 genes cause hereditary anemias (HA), a highly heterogeneous group of rare/low frequency disorders in which we included: hyporegenerative anemias, as congenital dyserythropoietic anemia (CDA) and Diamond-Blackfan anemia; hemolytic anemias due to erythrocyte membrane defects, as hereditary spherocytosis and stomatocytosis; hemolytic anemias due to enzymatic defects. The study describes the diagnostic workflow for HA, based on the development of two consecutive versions of a targeted-NGS panel, including 34 and 71 genes, respectively. Seventy-four probands from 62 unrelated families were investigated. Our study includes the most comprehensive gene set for these anemias and the largest cohort of patients described so far. We obtained an overall diagnostic yield of 64.9%. Despite 54.2% of cases showed conclusive diagnosis fitting well to the clinical suspicion, the multi-gene analysis modified the original clinical diagnosis in 45.8% of patients (nonmatched phenotype-genotype). Of note, 81.8% of nonmatched patients were clinically suspected to suffer from CDA. Particularly, 45.5% of the probands originally classified as CDA exhibited a conclusive diagnosis of chronic anemia due to enzymatic defects, mainly due to mutations in PKLR gene. Interestingly, we also identified a syndromic CDA patient with mild anemia and epilepsy, showing a homozygous mutation in CAD gene, recently associated to early infantile epileptic encephalopathy-50 and CDA-like anemia. Finally, we described a patient showing marked iron overload due to the coinheritance of PIEZO1 and SEC23B mutations, demonstrating that the multi-gene approach is valuable not only for achieving a correct and definitive diagnosis, but also for guiding treatment.

9.
Eur J Med Genet ; 61(11): 664-673, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29081386

RESUMO

Diamond-Blackfan anemia (DBA) is a rare congenital erythroblastopenia and inherited bone marrow failure syndrome that affects approximately seven individuals in every million live births. In addition to anemia, about 50% of all DBA patients suffer from various physical malformations of the face, hands, heart, or urogenital region. The disorder is almost exclusively driven by haploinsufficient mutations in one of several ribosomal protein (RP) genes, although for ∼30% of diagnosed patients no mutation is found in any of the known DBA-linked genes. Because DBA is such a rare disease with a particularly wide range of clinical phenotypes and molecular signatures, the development of collaborative efforts such as the ERARE-funded European DBA consortium (EuroDBA) has become imperative for DBA research. EuroDBA was founded in 2012 and brings together dedicated clinical and biological researchers of DBA from France, Italy, the Netherlands, Germany, Israel, Poland, and Turkey to achieve a number of goals including the consolidation of data in patient registries, establishment of minimal diagnostic criteria, and projects aimed at more fully describing the different mutations linked to DBA. This review will cover the history of the EuroDBA registries, the methods used by EuroDBA in the diagnosis of DBA, and how the consortium has successfully worked together towards the discovery of new DBA-linked genes and the better understanding their pathophysiological effects.

10.
Haematologica ; 103(2): 231-236, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29146706

RESUMO

Familial hemophagocytic lymphohistiocytosis is an autosomal recessive, life-threatening condition characterized by defective immune response. A retrospective analysis was performed on 57 patients diagnosed with familial hemophagocytic lymphohistiocytosis at Hacettepe University Pediatric Hematology Department, Ankara, Turkey. Mutation analysis was performed on 37 patients, and of these: 11 had UNC13D, 10 had PRF1 and 3 had STX11 gene mutation. Of these patients, 44% were found to have central nervous system involvement on admission and spinal cord involvement was also seen in 5 patients. Remission was achieved in 24 patients with the treatment, in a median time of 76 days (min-max: 15-705 days). Time to remission was prolonged 3.1 times in patients with a ferritin level 1500 mg/dL or more. When patients were grouped according to age [Group 1 (≤ 2 years), Group 2 (>2 years)]; patients in Group 1 had higher ferritin and aspartate aminotransferase levels but lower fibrinogen levels. The 5-year survival rate was also lower in Group 1. When patients in Group 1 were divided into two sub-groups according to hepatic involvement, the 5-year survival rate of patients who had hepatic involvement was significantly lower than those patients without hepatic involvement (0.7%, 27%, respectively) (P=0.002). The 5-year survival rate of patients who underwent hematopoietic stem cell transplantation was significantly higher than the patients who didn't (44%, 16%, respectively) (P=0.02). In conclusion, age two years and under, ferritin level above 1500 mg/dL, spinal cord or hepatic involvement should be considered as poor prognostic factors in familial hemophagocytic lymphohistiocytosis.

11.
Turk J Haematol ; 35(1): 12-18, 2018 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-28404539

RESUMO

OBJECTIVE: The Turkish Society of Pediatric Hematology set up a National Hemoglobinopathy Registry to demonstrate the demographic and disease characteristics of patients and assess the efficacy of a hemoglobinopathy control program (HCP) over 10 years in Turkey. MATERIALS AND METHODS: A total of 2046 patients from 27 thalassemia centers were registered, of which 1988 were eligible for analysis. This cohort mainly comprised patients with ß-thalassemia major (n=1658, 83.4%) and intermedia (n=215, 10.8%). RESULTS: The majority of patients were from the coastal areas of Turkey. The high number of patients in Southeastern Anatolia was due to that area having the highest rates of consanguineous marriage and fertility. The most common 11 mutations represented 90% of all ß-thalassemia alleles and 47% of those were IVS1-110(G->A) mutations. The probability of undergoing splenectomy within the first 10 years of life was 20%, a rate unchanged since the 1980s. Iron chelators were administered as monotherapy regimens in 95% of patients and deferasirox was prescribed in 81.3% of those cases. Deferasirox administration was the highest (93.6%) in patients aged <10 years. Of the thalassemia major patients, 5.8% had match-related hemopoietic stem cell transplantation with a success rate of 77%. Cardiac disease was detected as a major cause of death and did not show a decreasing trend in 5-year cohorts since 1999. CONCLUSION: While the HCP has been implemented since 2003, the affected births have shown a consistent decrease only after 2009, being at lowest 34 cases per year. This program failure resulted from a lack of premarital screening in the majority of cases. Additional problems were unawareness of the risk and misinformation of the at-risk couples. In addition, prenatal diagnosis was either not offered to or was not accepted by the at-risk families. This study indicated that a continuous effort is needed for optimizing the management of thalassemia and the development of strategies is essential for further achievements in the HCP in Turkey.


Assuntos
Talassemia/epidemiologia , Distribuição por Idade , Alelos , Demografia , Feminino , Humanos , Masculino , Programas de Rastreamento , Mutação , Fenótipo , Vigilância da População , Sistema de Registros , Talassemia/diagnóstico , Talassemia/prevenção & controle , Talassemia/terapia , Turquia/epidemiologia
12.
J Clin Invest ; 127(11): 4090-4103, 2017 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-28972538

RESUMO

Shwachman-Diamond syndrome (SDS) (OMIM #260400) is a rare inherited bone marrow failure syndrome (IBMFS) that is primarily characterized by neutropenia and exocrine pancreatic insufficiency. Seventy-five to ninety percent of patients have compound heterozygous loss-of-function mutations in the Shwachman-Bodian-Diamond syndrome (sbds) gene. Using trio whole-exome sequencing (WES) in an sbds-negative SDS family and candidate gene sequencing in additional SBDS-negative SDS cases or molecularly undiagnosed IBMFS cases, we identified 3 independent patients, each of whom carried a de novo missense variant in srp54 (encoding signal recognition particle 54 kDa). These 3 patients shared congenital neutropenia linked with various other SDS phenotypes. 3D protein modeling revealed that the 3 variants affect highly conserved amino acids within the GTPase domain of the protein that are critical for GTP and receptor binding. Indeed, we observed that the GTPase activity of the mutated proteins was impaired. The level of SRP54 mRNA in the bone marrow was 3.6-fold lower in patients with SRP54-mutations than in healthy controls. Profound reductions in neutrophil counts and chemotaxis as well as a diminished exocrine pancreas size in a SRP54-knockdown zebrafish model faithfully recapitulated the human phenotype. In conclusion, autosomal dominant mutations in SRP54, a key member of the cotranslation protein-targeting pathway, lead to syndromic neutropenia with a Shwachman-Diamond-like phenotype.


Assuntos
Doenças da Medula Óssea/genética , Insuficiência Pancreática Exócrina/genética , Lipomatose/genética , Neutropenia/congênito , Partícula de Reconhecimento de Sinal/genética , Animais , Criança , Análise Mutacional de DNA , Feminino , Estudos de Associação Genética , Humanos , Lactente , Masculino , Modelos Moleculares , Neutropenia/genética , Pâncreas Exócrino/metabolismo , Fenótipo , Domínios Proteicos , Partícula de Reconhecimento de Sinal/química , Peixe-Zebra
13.
Transfus Apher Sci ; 56(4): 539-543, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28818403

RESUMO

OBJECTIVES: Iron is taken into enterocytes at the duodenum via apical divalent metal-ion transporter 1 protein. Besides iron, divalent metal-ion transporter 1 also transports other divalent metals. We aimed to investigate blood heavy metal levels in patients with ineffective erythropoiesis. METHODS: Blood levels of heavy metals including Pb, Al, Cd, Cr, Co, Cu, and Zn were measured in patients with thalassemia major (TM), thalassemia intermedia (TI), congenital dyserythropoietic anemia (CDA), and age- and sex-matched healthy controls. RESULTS: Blood samples were obtained from 68 patients (51 patients with TM, 8 with TI, 9 with CDA), and a control group that included 65 volunteers. Patients with TM were found to have lower Al, Pb, and Zn, and higher Cd levels compared with the control group. The patients treated with deferasirox were further analyzed and Pb and Zn levels were found lower compared with the control group. DISCUSSION: Patients with TM had tendency to have elevated levels of plasma cadmium; however, the median level was not at a toxic level. Increased metal-ion transporter 1 activity may cause heavy metal accumulation, but deferasirox chelation may be protective against heavy metals besides iron.


Assuntos
Anemia Diseritropoética Congênita/sangue , Eritropoese , Metais Pesados/sangue , Talassemia beta/sangue , Adolescente , Adulto , Anemia Diseritropoética Congênita/tratamento farmacológico , Benzoatos/administração & dosagem , Criança , Pré-Escolar , Deferasirox , Feminino , Humanos , Masculino , Triazóis/administração & dosagem , Talassemia beta/tratamento farmacológico
16.
Pediatr Radiol ; 47(2): 146-153, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27796469

RESUMO

BACKGROUND: Computed tomography (CT) is commonly used to detect pulmonary infection in immunocompromised children. OBJECTIVE: To compare MRI and multidetector CT findings of pulmonary abnormalities in immunocompromised children. MATERIALS AND METHODS: Seventeen neutropaenic children (6 girls; ages 2-18 years) were included. Non-contrast-enhanced CT was performed with a 64-detector CT scanner. Axial and coronal non-enhanced thoracic MRI was performed using a 1.5-T scanner within 24 h of the CT examination (true fast imaging with steady-state free precession, fat-saturated T2-weighted turbo spin echo with motion correction, T2-weighted half-Fourier single-shot turbo spin echo [HASTE], fat-saturated T1-weighted spoiled gradient echo). Pulmonary abnormalities (nodules, consolidations, ground glass opacities, atelectasis, pleural effusion and lymph nodes) were evaluated and compared among MRI sequences and between MRI and CT. The relationship between MRI sequences and nodule sizes was examined by chi- square test. RESULTS: Of 256 CT lesions, 207 (81%, 95% confidence interval [CI] 76-85%) were detected at MRI. Of 202 CT-detected nodules, 157 (78%, 95% CI 71-83%) were seen at motion-corrected MRI. Of the 1-5-mm nodules, 69% were detected by motion-corrected T2-weighted MRI and 38% by HASTE MRI. CONCLUSION: Sensitivity of MRI (both axial fat-saturated T2-weighted turbo spin echo with variable phase encoding directions (BLADE) images and HASTE sequences) to detect pulmonary abnormalities is promising.


Assuntos
Neoplasias Hematológicas/complicações , Hospedeiro Imunocomprometido , Pneumopatias/diagnóstico por imagem , Pneumopatias/microbiologia , Imagem por Ressonância Magnética/métodos , Tomografia Computadorizada Multidetectores/métodos , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Estudos Prospectivos , Sensibilidade e Especificidade
17.
Hematology ; 22(4): 248-251, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-27809710

RESUMO

BACKGROUND: Iron chelation therapy is one of the mainstays of the management of the patients with ß-thalassemia (BT) major. Deferasirox is an oral active iron chelating agent. Proteinuria is one of the potential renal adverse effects of deferasirox, and monthly follow-up for proteinuria is suggested by Food and Drug Administration and European Medicine Agency. METHODS: We aimed to investigate the necessity for monthly monitoring for proteinuria among patients with BT on deferasirox. A retrospective laboratory and clinic data review was performed for patients with BT major or intermedia who were treated with deferasirox chelation therapy. All patients were monitored for proteinuria for every 3 or 4 weeks after the initiation of deferasirox with serum creatinine and spot urine protein/creatinine ratios. RESULTS: The median follow-up time of the 37 (36 BT major and one BT intermedia) patients was 44 months. Seven patients (18.9%) developed significant proteinuria (ratio ≥0.8). Of the 1490 measurements, 12 tests (0.8%) were proteinuric. Urine proteinuria resolved in all of the patients during the follow-up. The risk of proteinuria was higher at ages below a cut-off point of 23 years (p = 0.019). Patients, who were on deferasirox at doses above a cut-off dose of 29 mg/kg/day, were found to have higher risk of proteinuria development (p = 0.004). CONCLUSION: Proteinuria resolves without any complication or major intervention according to our results. Potentially more risky groups (age below 23 years old and receivers above a dose of 29 mg/kg/day) might be suggested to be followed monthly, besides monitoring all of the patients.


Assuntos
Benzoatos/efeitos adversos , Proteinúria/urina , Triazóis/efeitos adversos , Talassemia beta/tratamento farmacológico , Talassemia beta/urina , Adolescente , Adulto , Benzoatos/uso terapêutico , Criança , Pré-Escolar , Deferasirox , Feminino , Humanos , Masculino , Proteinúria/induzido quimicamente , Proteinúria/diagnóstico , Estudos Retrospectivos , Triazóis/uso terapêutico , Adulto Jovem , Talassemia beta/sangue
18.
J Pediatr Hematol Oncol ; 39(3): e143-e149, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-27984354

RESUMO

Attendance to follow-up care after completion of cancer treatment is an understudied area. We examined demographic, clinical, and socioeconomic predictors of follow-up by pediatric cancer patients at a large center in 442 newly diagnosed patients using multivariable logistic regression analyses. Patients who did not return to clinic for at least 1000 days were considered lost to follow-up. Two hundred forty-two (54.8%) patients were lost. In multivariable analyses, the following variables were independent predictors of being lost to follow-up: treatment with surgery alone (odds ratio [OR]=6.7; 95% confidence interval [CI], 3.1-14.9), older age at diagnosis (reference, 0 to 4; ages, 5 to 9: OR=1.8, 95% CI, 1.1-3; ages, 10 to 14: OR=3.3; CI, 1.8-6.1; and ages, 15 and above: OR=4.8; CI, 2.1-11.7), lack of history of stem cell transplantation (OR=2, 95% CI, 1.04-3.7) and lack of insurance (OR=3.4; CI, 1.2-9.2). Hispanic patients had the best follow-up rates (53.7%) compared to whites and blacks (P=0.03). Attendance to long-term follow-up care is suboptimal in childhood cancer survivors. Predictors that were associated with nonattendance can be used to design targeted interventions to improve follow-up care for survivors of pediatric cancer.


Assuntos
Assistência ao Convalescente/normas , Neoplasias/terapia , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Adolescente , Criança , Pré-Escolar , Humanos , Lactente , Recém-Nascido , Análise Multivariada , Aceitação pelo Paciente de Cuidados de Saúde/etnologia , Cooperação do Paciente/etnologia , Cooperação do Paciente/estatística & dados numéricos , Fatores de Risco , Sobreviventes
19.
Rheumatol Int ; 36(10): 1421-9, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27510530

RESUMO

Macrophage activation syndrome (MAS) is a hyper-inflammatory disorder secondary to a rheumatic disease such as systemic juvenile idiopathic arthritis (SJIA) and systemic lupus erythematosus (SLE). We aimed to present the characteristics of our pediatric MAS patients. Clinical features, laboratory parameters, treatment, and outcome of 34 patients (28 SJIA; six SLE; 37 MAS episodes) followed at a tertiary health center between 2009 and 2015 were retrospectively reviewed. The median age at MAS onset was 11 years. More SJIA patients had MAS at disease onset than SLE patients (53.6 vs. 16.7 %). Fever, high C-reactive protein and hyperferritinemia were present in all MAS episodes. Rash was less (p = 0.03), and fatigue was more frequent (p = 0.042) in SLE than SJIA patients. All received corticosteroids. Cyclosporine was given in 74.2 % of SJIA-MAS; 66.7 % of SLE-MAS episodes. Intravenous immunoglobulin, anakinra, or etoposide was administered during 67.7; 41.9; 32.3 % of SJIA-MAS and 33.3; 33.3; 50 % of SLE-MAS episodes, respectively. Plasmapheresis was performed during 41.9 % of SJIA-MAS and 33.3 % of SLE-MAS episodes. The mortality rate was 11.8 % (n = 4;3 SJIA, 1 SLE). Hepatosplenomegaly was more frequent (p = 0.005), and plasmapheresis was performed more frequently (p = 0.021) in the patients who died compared to the cured patients. The median duration between symptom onset and admission to our hospital was longer among the patients who died (16.5 vs. 7 days; p = 0.049). Our patients' characteristics were similar to the reported cases, but our mortality rate is slightly higher probably due to late referral to our center. Early diagnosis and effective treatment are crucial to prevent mortality.


Assuntos
Artrite Juvenil/complicações , Lúpus Eritematoso Sistêmico/complicações , Síndrome de Ativação Macrofágica/complicações , Adolescente , Corticosteroides/uso terapêutico , Artrite Juvenil/tratamento farmacológico , Criança , Pré-Escolar , Ciclosporina/uso terapêutico , Fadiga/complicações , Feminino , Humanos , Imunossupressores/uso terapêutico , Lactente , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Síndrome de Ativação Macrofágica/tratamento farmacológico , Masculino , Estudos Retrospectivos , Resultado do Tratamento
20.
J Pediatr Hematol Oncol ; 38(7): 539-43, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-27548336

RESUMO

The aim was to evaluate baseline demographic, clinical, and laboratory characteristics, treatment modalities, and outcome of children with idiopathic hypereosinophilic syndrome (HES) followed up in our center. Children who fulfilled the criteria of idiopathic HES followed up at Hacettepe University Faculty of Medicine, Pediatric Hematology Department between June 2004 and October 2013 were included in this study. Medical records of all children with idiopathic HES were reviewed to obtain regarding data. The mean age of 6 children with idiopathic HES was 52.8±44.3 months (13 to 132 mo) at diagnosis. Among 6 children with idiopathic HES; 2 had pulmonary involvement; 1 had cardiac and pulmonary involvement and splenomegaly; 1 had cardiac involvement and hepatosplenomegaly; 1 had cardiac and central nervous system involvement; and 1 had skin involvement. The mean follow-up duration was 36.5±31.4 months. Methyl prednisolone (MP) was used for the first-line therapy. Complete response was achieved with MP in 3 children. All steroid responsive children are alive; whereas 3 children who did not respond to MP had expired. In conclusion, cardiac and pulmonary involvement is the major causes of mortality in HES. Resistance to steroid therapy indicates poor prognosis.


Assuntos
Síndrome Hipereosinofílica/terapia , Criança , Pré-Escolar , Feminino , Transplante de Células-Tronco Hematopoéticas , Humanos , Lactente , Masculino , Metilprednisolona/uso terapêutico
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