Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 86
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
2.
Acta Biomed ; 90(3): 225-237, 2019 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-31580308

RESUMO

BACKGROUND: More than five decades ago, thalassemia major (TDT) was fatal in the first decade of life. Survival and quality of life have improved progressively thanks to the implementation of a significant advance in diagnostic and therapeutic methods, consisting mainly of a frequent transfusion program combined with intensive chelation therapy. Improvement also includes imaging methods used to measure liver and cardiac iron overload. Improved survival has led to a growing number of adults requiring specialised care and counselling for specific life events, such as sexual maturity and acquisition of a family. AIMS OF THE STUDY: The main aim is to present the results of a survey on the marital and paternity status in a large population of adult males with TDT and NTDT living in countries with a high prevalence of thalassemia and a review of current literature using a systematic search for published studies. RESULTS: Ten out of 16 Thalassemia Centres (62.5%) of the ICET-A Network, treating a total of 966 male patients, aged above 18 years with ß- thalassemias (738 TDT and 228 NTDT), participated in the study. Of the 966 patients, 240 (24.8%) were married or lived with partners, and 726 (75.2%) unmarried. The mean age at marriage was 29.7 ± 0.3 years. Of 240 patients, 184 (76.6%) had children within the first two years of marriage (2.1 ± 0.1 years, median 2 years, range 1.8 - 2.3 years). The average number of children was 1.32 ± 0.06 (1.27 ± 0.07 in TDT patients and 1.47 ± 0.15 in NTDT patients; p: >0.05). Whatever the modality of conception, 184 patients (76.6%) had one or two children and 1 NTDT patient had 6 children. Nine (4.8%) births were twins. Of 184 patients, 150 (81.5%) had natural conception, 23 (12.5%) required induction of spermatogenesis with gonadotropins (hCG and hMG), 8 (4.3%) needed intracytoplasmic sperm injection (ICSI) and 3 adopted a child. 39 patients with TDT and NTDT asked for medical help as they were unable to father naturally: 7 TDT patients (17.9%) were azoospermic, 17 (37.7%) [13 with TDT and 4 with NTDT] had dysspermia and 15 (33.3%) [13 with TDT and 2 with NTDT] had other "general medical and non-medical conditions". CONCLUSIONS: Our study provides detailed information in a novel area where there are few contemporary data. Understanding the aspects of male reproductive health is important for physicians involved in the care of men with thalassemias to convey the message that prospects for fatherhood are potentially good due to progressive improvements in treatment regimens and supportive care.

3.
Surg Neurol Int ; 10: 75, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31528413

RESUMO

Background: Hemangiopericytoma and solitary fibrous tumor (HPC/SFT) are considered to be one category according to the WHO 2016 classification of central nervous system tumors. HPC/SFT are subdivided into infantile (congenital) and adult type. Both are extremely rare entities, with little knowledge about etiology, prognosis, and optimal therapeutic strategy. Case Description: A 10-day-old girl was referred to our neurosurgical department due to hypotonia, palsy of the right oculomotor nerve, and prominent frontal fontanel. Imaging studies revealed a large occupying mass in the right middle cerebral fossa and the suprasellar cisterns. Only a subtotal resection of the tumor was possible, and postoperatively, she underwent chemotherapy (CHx). After a 3-year follow-up, the girl has minimum neurologic signs and receives no medications, and she can walk when she is supported. Conclusion: Congenital HPC/SFT is considered to have a benign behavior with a good prognosis. Treatment with gross total resection, when it is feasible, is the key to a good prognosis and low rates of recurrence. However, there is no consensus on the therapeutic strategy of a HPC/SFT, which is difficult to be completely resected. Literature lacks a therapeutic algorithm for these tumors, and thus, more clinical studies are needed to reach a consensus.

4.
J Neurooncol ; 145(1): 177-184, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31522324

RESUMO

INTRODUCTION: Diffuse intrinsic pontine glioma (DIPG) is a rare clinically, neuro-radiologically, and molecularly defined malignancy of the brainstem with a median overall survival of approximately 11 months. Our aim is to evaluate the current tendency for its treatment in Europe in order to develop (inter)national consensus guidelines. METHODS: Healthcare professionals specialized in DIPG were asked to fill in an online survey with questions regarding usual treatment strategies at diagnosis and at disease progression in their countries and/or their centers, respectively. RESULTS: Seventy-four healthcare professionals responded to the survey, of which 87.8% were pediatric oncologists. Only 13.5% of the respondents biopsy all of their patients, 41.9% biopsy their patients infrequently. More than half of the respondents (54.1%) treated their patients with radiotherapy only at diagnosis, whereas 44.6% preferred radiotherapy combined with chemotherapy. When the disease progresses, treatment strategies became even more diverse, and the tendency for no treatment increased from 1.4% at diagnosis to 77.0% after second progression. 36.5% of the healthcare professionals treat children younger than 3 years differently than older children at diagnosis. This percentage decreased, when the disease progresses. Most of the participants (51.4%) included less than 25% of their patients in clinical trials. CONCLUSION: This survey demonstrates a large heterogeneity of treatment regimens, especially at disease progression. We emphasize the need for international consensus guidelines for the treatment of DIPG, possible by more collaborative clinical trials.

5.
Postgrad Med ; 131(7): 445-452, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31443616

RESUMO

Given the complexity of neurocutaneous syndromes, a multidisciplinary approach has been advocated in order to provide optimum care. Subjects and Methods: Retrospective analysis of a cohort of 157 patients during a 3-year period, seen at a newly developed neurocutaneous clinic in a pediatric tertiary care hospital in Athens (Greece); and systematic chart review of the patients diagnosed with neurofibromatosis type 1 during this time period. Results: The most frequent neurocutaneous syndromes were neurofibromatosis type 1 (NF1) in 89 patients and tuberous sclerosis complex in 17. In 20.38% of patients a neurocutaneous syndrome was not confirmed. Approximately 2/3 of the NF1 patients underwent genetic analysis, and for 76.67% of them, a pathogenic mutation on the NF1 gene was revealed. Eighty-one patients manifested with generalized NF1 and eight with mosaic NF1. Dermatological manifestations included café-au-lait macules in all patients, followed by axillary and/or inguinal freckling (n = 57), external plexiform neurofibromas (n = 17), and cutaneous and subcutaneous neurofibromas (n = 11). Approximately half of patients had learning disabilities and attention deficit hyperactivity disorder, followed by mental retardation (n = 9), autistic spectrum disorders (n = 4), headaches (n = 3) and seizures (n = 2). Neuroimaging showed characteristic areas of hyperintensity on T2-weighted images in 74.07% of patients and optic pathway glioma in 19.75%. Two patients developed malignant peripheral sheath nerve tumor. Conclusions: Neurocutaneous syndromes are clinically heterogeneous and the surveillance of potential clinical complications is challenging. The availability of genetic diagnosis and novel imaging methods in this group of disorders is likely to further expand their clinical spectrum. Guidelines for assessment and management will need to be modified based on new available data.


Assuntos
Neurofibromatose 1/fisiopatologia , Equipe de Assistência ao Paciente , Esclerose Tuberosa/fisiopatologia , Adolescente , Transtorno do Deficit de Atenção com Hiperatividade/complicações , Transtorno do Espectro Autista/complicações , Manchas Café com Leite/complicações , Criança , Pré-Escolar , Estudos de Coortes , Dermatologistas , Feminino , Genes da Neurofibromatose 1 , Testes Genéticos , Genética Médica , Grécia , Humanos , Lactente , Deficiência Intelectual/complicações , Masculino , Mosaicismo , Síndromes Neurocutâneas/genética , Síndromes Neurocutâneas/fisiopatologia , Síndromes Neurocutâneas/terapia , Neurofibroma Plexiforme/complicações , Neurofibromatose 1/complicações , Neurofibromatose 1/genética , Neurofibromatose 1/terapia , Neurologistas , Neuropsicologia , Oncologistas , Oftalmologistas , Cirurgiões Ortopédicos , Ambulatório Hospitalar , Pediatras , Radiologia , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/fisiopatologia , Neoplasias Cutâneas/terapia , Esclerose Tuberosa/complicações , Esclerose Tuberosa/genética , Esclerose Tuberosa/terapia
7.
Leuk Res ; 83: 106177, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31261022

RESUMO

Acute Lymphoblastic Leukemia (ALL) is a malignancy of the immature lymphoid cells mainly associated with numerical and structural chromosomal aberrations. The current standard for profiling the diverse genetic background comprises a combination of conventional karyotype and FISH analysis for the most common translocations, albeit with many limitations. Chromosomal Microarray Analysis (CMA) is a high throughput whole genome method that is gradually implemented in routine clinical practice, but not many studies have compared the two methods. Here we aim to investigate the added benefits of utilizing the high resolution 2 x 400 K G3 CGH + SNP CMA platform in routine diagnostics of pediatric ALL. From the 29 bone marrow samples that were analyzed, CMA identified clinically relevant findings in 83%, while detecting chromosomal aberrations in 75% of the patients with normal conventional karyotype. The most common finding was hyperdiploidy (20%), and the most common submicroscopic aberration involved CDKN2A/B genes. The smallest aberration detected was a 9 kb partial NF1 gene duplication. The prognosis of the patients when combining conventional cytogenetics and CMA was either changed or enhanced in 66% of the cases. A rare duplication possibly indicative of a cryptic ABL1-NUP214 fusion gene was found in one patient. We conclude that CMA, when combined with conventional cytogenetic analysis, can significantly enhance the genetic profiling of patients with pediatric ALL in a routine clinical setting.

8.
Head Neck ; 41(9): 3422-3433, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31228308

RESUMO

BACKGROUND: This systematic review summarizes the prevalence of dental defects after chemo and radiation therapy and correlates the findings with specific characteristics of each treatment modality. METHODS: Database search was performed for studies reporting dental late effects of chemo and radiation therapy. After data extraction and risk of bias assessment, prevalence of crown and root defects was assessed. Correlations between each defect and the characteristics of the antineoplastic treatment were performed. RESULTS: Sixteen nonrandomized studies were included, yielding a total of 1300 patients with a mean age at diagnosis of 4.5 years. Results reported that root defects were more common than crown defects. The most common root defect was impaired root growth and microdontia the most common crown defect. Age, radiation dose and field were statistically associated with higher prevalence of dental defects. CONCLUSION: Defects were associated with combination of chemotherapy and radiotherapy, as used in current therapeutic antineoplastic modalities.

9.
Pediatr Hematol Oncol ; 36(3): 173-186, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31215284

RESUMO

Respiratory infections in oncology are both common and potentially severe. However, there is still a gap in the literature, regarding the epidemiology of viral respiratory infections in children with cancer. We prospectively enrolled 224 patients, from September 2012 to August 2015. The cohort included children with hematologic or solid malignancies receiving chemotherapy, or undergoing hemopoietic stem cell transplantation, outpatients/inpatients exhibiting signs/symptoms of febrile/afebrile upper/lower respiratory infection. Viral infection was diagnosed by detection of ≥1 viruses from a sample at time of enrollment, using the CLART® PneumoVir kit (GENOMICA, Spain). Α detailed questionnaire including demographics and medical history was also completed. Samples were processed in batches, results were communicated as soon as they became available. Children recruited in whom no virus was detected composed the no virus detected group. Viral prevalence was 38.4% in children presenting with respiratory illness. A single virus was found in 30.4%, with RSV being the most frequent. Viral coinfections were detected in 8%. Children with viral infection were more likely to be febrile upon enrollment and to present with lower respiratory signs/symptoms. They had longer duration of illness and they were more likely to receive antibiotics/antifungals. Only 22% of children with influenza received oseltamivir. Mortality was low (2.7%), however, pediatric intensive care unit (PICU) admission and death were correlated with virus detection. In our study mortality was low and PICU admission was related to virus identification. Further research is needed to clarify whether antibiotics in virus-proven infection are of value and underline the importance of oseltamivir's timely administration in influenza.


Assuntos
Hospitalização , Influenza Humana , Neoplasias , Oseltamivir/administração & dosagem , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Influenza Humana/diagnóstico , Influenza Humana/tratamento farmacológico , Influenza Humana/epidemiologia , Masculino , Neoplasias/epidemiologia , Neoplasias/terapia , Prevalência , Estudos Prospectivos
10.
Curr Mol Med ; 19(5): 335-341, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30868952

RESUMO

BACKGROUND: Thalassemia major (TM) patients eventually face many new health conditions, including endocrinopathies and low bone mineral density, usually observed in the aging general population. OBJECTIVE: The aim of the current study was to evaluate the biomarkers of bone remodeling in TM patients and to compare them with both osteoporotic and healthy population, in order to investigate the new therapeutic paths. METHODS: Sixty-four patients with TM (32 men and 32 women) participated in the study. The patients were evaluated with dual-energy X-ray absorptiometry (DXA) of the lumbar spine and femoral neck and with markers of bone remodeling including receptor activator of nuclear factor kappa-Β ligand (RANKL), osteoprotegerin (OPG), C-terminal telopeptide (CTX), and sclerostin. Results were compared with those from 12 postmenopausal women with osteoporosis and 12 women with normal bone mineral density. RESULTS: The statistical analysis of the biochemical markers of bone metabolism revealed overall significant differences between the three groups only for RANKL and OPG/RANKL (p=0.049 and p=0.009). RANKL was higher and OPG/RANKL was lower in TM patients compared to osteoporosis group. CONCLUSION: Patients with TM do not have a higher probability of suffering from osteoporosis from the general population. However, some markers of osteoclast activity differ between patients with TM and osteoporosis, indicating the possible differences in terms of anti-osteoporotic treatment. The lack of significant differences among the three groups in regards to the levels of CTX and sclerostin may indicate the potential efficacy of the current osteoporotic treatment also for TM patients.

11.
Ann Hematol ; 98(3): 775-779, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30683996

RESUMO

Streptococcus pnemoniae is a major cause of morbidity and mortality among splenectomised patients with ß-thalassemia major. We have previously shown that a 13-valent pneumococcal conjugate vaccine (PCV13) induces robust early immune responses in such patients, while history of repeated immunisations with the 23-valent polysaccharide pneumococcal vaccine (PPSV23) results in attenuation of the response to PCV13. However, the duration of vaccine-induced protection in splenectomised thalassemic patients and the associated need for booster immunisation remains unclear. In the current study, we enumerate antibody persistence 5 years post-PCV13 and investigate any correlation with early immune response and immunisation history. Pneumococcal serotype (PS)-specific antibodies against 5 vaccine antigens were measured 5 years post-PCV13 in 34 asplenic adults with ß-thalassemia. PS-specific antibodies against 5 vaccine serotypes had declined significantly at 5 years post-PCV13 (year 5).Year 5 antibody titres remained above baseline for PS9V, 19A and19F, returned to baseline for PS23F, and dropped below baseline for PS3 (p < 0.001).Year 5 antibodies were positively correlated with day 28 antibody titres, while no correlation was found with early memory B cell response. Previous PPSV23 history was correlated with impaired antibody persistence against serotype 19A. Antibody levels dropped significantly but remained at protective levels 5 years post-PCV13.We propose that asplenic patients with ß-thalassemia may benefit from measurement of antipneumococcal antibodies after 5 years post-PCV13 as they may eventually be in need for booster pneumococcal vaccination. Clinical Trials Registration ID: www.clinicaltrials.gov NCT01846923.


Assuntos
Anticorpos Antibacterianos/sangue , Infecções Pneumocócicas , Vacinas Pneumocócicas/administração & dosagem , Esplenectomia , Streptococcus pneumoniae , Talassemia beta , Adulto , Feminino , Seguimentos , Humanos , Imunização Secundária , Masculino , Pessoa de Meia-Idade , Infecções Pneumocócicas/sangue , Infecções Pneumocócicas/etiologia , Infecções Pneumocócicas/prevenção & controle , Fatores de Tempo , Talassemia beta/sangue , Talassemia beta/complicações , Talassemia beta/cirurgia
12.
Lancet Child Adolesc Health ; 3(1): 2-3, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30455111
13.
Am J Hematol ; 94(2): 177-183, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30394570

RESUMO

This study demonstrates the quantitative characteristics of the first patient-reported outcome (PRO) tool developed for patients with nontransfusion-dependent ß-thalassemia (NTDT), the NTDT-PRO© . A multicenter validation study was performed over 24 weeks, involving 48 patients from Italy, Lebanon, Greece, and Thailand. Most patients were female (68.8%), with a median age of 34.5 years (range, 18-52); 66.7% were diagnosed with ß-thalassemia intermedia, and median time since diagnosis was 22 years (range, 0-43). The NTDT-PRO comprises 6 items across 2 domains (Tiredness/Weakness and Shortness of Breath [SoB]), and was valid and reliable, with good consistency. At baseline, most patients reported symptoms as present via the NTDT-PRO, and were highly compliant, ≥90% completing the NTDT-PRO tool. In a pairwise correlation analysis, all items were positively correlated. Correlations between NTDT-PRO and existing tools-36-Item Short Form Health Survey version 2 (SF-36v2) and Functional Assessment of Cancer Therapy-Anemia (FACT-An)-were assessed at weeks 1, 3, and 12; robust correlations were seen between SoB and SF-36v2-Vitality (rs = -0.53), and between SoB and Fact-An-Fatigue Experience (rs = -0.66) at week 1. Internal consistency was high for both Tiredness/Weakness (Cronbach alpha, 0.91) and SoB (Spearman-Brown coefficient, 0.78); intraclass correlation coefficients were high (Tiredness/Weakness, 0.88 and 0.97; SoB, 0.92 and 0.98), demonstrating stability. Further studies are required to fully support the validity of this tool, this study demonstrated the usefulness of the NTDT-PRO in the clinical setting and for longitudinal clinical research, particularly in trials where patient health-related quality of life is expected to change.


Assuntos
Medidas de Resultados Relatados pelo Paciente , Talassemia beta/patologia , Adolescente , Adulto , Dispneia , Fadiga , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Qualidade de Vida , Adulto Jovem
14.
Am J Hematol ; 94(2): 171-176, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30394579

RESUMO

ß-Thalassemia, a hereditary blood disorder caused by reduced or absent synthesis of the ß-globin chain of hemoglobin, is characterized by ineffective erythropoiesis, and can manifest as nontransfusion-dependent thalassemia (NTDT) or transfusion-dependent thalassemia (TDT). Many patients with NTDT develop a wide range of serious complications that affect survival and quality of life (QoL). Patient-reported outcomes (PRO), including health-related QoL (HRQoL), are important tools for determining patient health impairment and selecting appropriate treatment. However, there are currently no disease-specific PRO tools available to assess symptoms related to chronic anemia experienced by patients with NTDT. This study aimed to develop a new, US Food and Drug Administration (FDA)-compliant PRO of chronic anemia symptoms, the NTDT-PRO© tool, for use in patients with NTDT. Participants had a median age of 36 years (range, 18-47) and 60% were female. The initial development of the NTDT-PRO tool involved concept-elicitation interviews with 25 patients from 3 centers (in Lebanon, Greece, and Canada); subsequent interview discussions and clinical input resulted in the generation of 9 items for inclusion in the draft NTDT-PRO. Following a round of cognitive interviews involving 21 patients from 2 centers (in Lebanon and Greece), 4 items (Pain, Headaches, Ability to Concentrate, and Paleness) were removed from the draft NTDT-PRO. The final NTDT-PRO comprises 6 items that measure Tiredness, Weakness, and Shortness of Breath, with or without Physical Activity. The NTDT-PRO is a new disease-specific HRQoL tool for patients with NTDT, developed using a thorough methodology based on FDA 2009 PRO development guidelines.


Assuntos
Medidas de Resultados Relatados pelo Paciente , Talassemia/patologia , Adolescente , Adulto , Feminino , Humanos , Entrevistas como Assunto , Masculino , Pessoa de Meia-Idade , Qualidade de Vida , Estados Unidos , United States Food and Drug Administration , Adulto Jovem
15.
Ann Hematol ; 98(1): 55-66, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30196444

RESUMO

National registries constitute an invaluable source of information and contribute to the improvement of hemoglobinopathy management. Herein, we present the second updated report of the National Registry for Haemoglobinopathies in Greece (NRHG) and critically discuss the time trends in demographics, affected births, and causes of mortality. Thirty-eight Greek hemoglobinopathy units reported data from diagnosis to the last follow-up or death by retrospectively completing an electronic form. Four thousand thirty-two patients were eligible for inclusion; more than half of them had thalassaemia major. Compared to the previous report, a reduction in the total number of all hemoglobinopathies except for hemoglobinopathy "Η" was evident. The total number of affected births was also reduced; most of them were attributable to diagnostic errors and lack of awareness. Importantly, data on iron overload are reported for the first time; although most patients had low or moderate liver iron concentration (LIC) values, a non-negligible proportion of patients had high LIC. The burden due to heart iron overload was less prominent. Cardiac- and liver-related complications are the major causes of morbidity and mortality. From 2000 to 2015, a decrease in heart-related deaths along with an increase in liver-associated fatalities was observed. The Hellenic Prevention Program along with advances in chelation regimens and iron status monitoring have resulted in improved patient outcomes. The NRHG gives insight into the effectiveness of prevention programs, the therapeutic management of hemoglobinopathies and associated outcomes. NRHG may contribute to the formulation of a roadmap for hemoglobinopathies in Europe and promote the implementation of effective public health policies.


Assuntos
Hemoglobinopatias/epidemiologia , Sistema de Registros , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Feminino , Grécia/epidemiologia , Cardiopatias/sangue , Cardiopatias/epidemiologia , Cardiopatias/etiologia , Hemoglobinopatias/complicações , Hemoglobinopatias/metabolismo , Humanos , Lactente , Ferro/metabolismo , Sobrecarga de Ferro/sangue , Sobrecarga de Ferro/epidemiologia , Sobrecarga de Ferro/etiologia , Fígado/metabolismo , Hepatopatias/sangue , Hepatopatias/epidemiologia , Hepatopatias/etiologia , Masculino , Pessoa de Meia-Idade
16.
Health Qual Life Outcomes ; 16(1): 216, 2018 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-30453981

RESUMO

BACKGROUND: Adherence to long-term chelation therapy in transfusion-dependent patients is critical to prevent iron overload-related complications. Once-daily deferasirox dispersible tablets (DT) have proven long-term efficacy and safety in patients ≥2 years old with chronic transfusional iron overload. However, barriers to optimal adherence remain, including palatability, preparation time, and requirements for fasting state. A new film-coated tablet (FCT) formulation was developed, swallowed once daily (whole/crushed) with/without a light meal. METHODS: The open-label, Phase II ECLIPSE study evaluated patient-reported outcomes (PROs) in transfusion-dependent thalassemia or lower-risk myelodysplastic syndromes patients randomized 1:1 to receive deferasirox DT or FCT over 24 weeks as a secondary outcome of the study. Three PRO questionnaires were developed to evaluate both deferasirox formulations: 1) Modified Satisfaction with Iron Chelation Therapy Questionnaire; 2) Palatability Questionnaire; 3) Gastrointestinal (GI) Symptom Diary. RESULTS: One hundred seventy three patients were enrolled; 87 received the FCT and 86 the DT formulation. FCT recipients consistently reported better adherence (easier to take medication, less bothered by time to prepare medication and waiting time before eating), greater satisfaction/preference (general satisfaction and with administration of medicine), and fewer concerns (less worry about not swallowing enough medication, fewer limitations in daily activities, less concern about side effects). FCT recipients reported no taste or aftertaste and could swallow all their medicine with an acceptable amount of liquid. GI summary scores were low for both formulations. CONCLUSIONS: These findings suggest a preference in favor of the deferasirox FCT formulation regardless of underlying disease or age group. Better patient satisfaction and adherence to chelation therapy may reduce iron overload-related complications. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02125877; registered April 26, 2014.


Assuntos
Desferroxamina/uso terapêutico , Quelantes de Ferro/uso terapêutico , Síndromes Mielodisplásicas/tratamento farmacológico , Medidas de Resultados Relatados pelo Paciente , Satisfação do Paciente , Talassemia/tratamento farmacológico , Adulto , Transfusão de Sangue , Terapia por Quelação/métodos , Feminino , Humanos , Sobrecarga de Ferro/prevenção & controle , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/psicologia , Qualidade de Vida , Talassemia/psicologia
17.
Eur J Haematol ; 101(3): 272-282, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29904950

RESUMO

Effective iron chelation therapy is an important part of treatment in patients with transfusion-dependent thalassaemia and lower-risk myelodysplastic syndromes (MDS). Key strategies for optimising iron chelation therapy include ensuring good adherence and preventing and managing adverse events (AEs). Good adherence to iron chelation therapy with deferoxamine and deferasirox has been linked to improved survival and/or reductions in complications related to iron overload; however, maintaining good adherence to iron chelators can be challenging. Patients with transfusion-dependent thalassaemia or lower-risk MDS showed better adherence to the deferasirox film-coated tablet (FCT) formulation than to the deferasirox dispersible tablet formulation in the ECLIPSE trial, reflecting in part the improved palatability and convenience of deferasirox FCT. As well as affecting adherence, AEs may lead to dose reduction, interruption or discontinuation, resulting in suboptimal iron chelation therapy. Preventing and successfully managing AEs may help limit their impact on adherence, and following dosage and administration recommendations for iron chelators such as deferasirox may help minimise AEs and optimise treatment in patients with transfusion-dependent thalassaemia and lower-risk MDS.


Assuntos
Deferasirox/uso terapêutico , Quelantes de Ferro/uso terapêutico , Sobrecarga de Ferro/tratamento farmacológico , Sobrecarga de Ferro/etiologia , Síndromes Mielodisplásicas/complicações , Talassemia/complicações , Transfusão de Sangue/métodos , Terapia por Quelação , Deferasirox/administração & dosagem , Deferasirox/efeitos adversos , Gerenciamento Clínico , Humanos , Quelantes de Ferro/administração & dosagem , Quelantes de Ferro/efeitos adversos , Testes de Função Hepática , Adesão à Medicação , Síndromes Mielodisplásicas/diagnóstico , Síndromes Mielodisplásicas/terapia , Talassemia/diagnóstico , Talassemia/terapia , Resultado do Tratamento
18.
Blood ; 132(5): 469-483, 2018 08 02.
Artigo em Inglês | MEDLINE | ID: mdl-29891534

RESUMO

Chuvash polycythemia is an autosomal recessive form of erythrocytosis associated with a homozygous p.Arg200Trp mutation in the von Hippel-Lindau (VHL) gene. Since this discovery, additional VHL mutations have been identified in patients with congenital erythrocytosis, in a homozygous or compound-heterozygous state. VHL is a major tumor suppressor gene, mutations in which were first described in patients presenting with VHL disease, which is characterized by the development of highly vascularized tumors. Here, we identify a new VHL cryptic exon (termed E1') deep in intron 1 that is naturally expressed in many tissues. More importantly, we identify mutations in E1' in 7 families with erythrocytosis (1 homozygous case and 6 compound-heterozygous cases with a mutation in E1' in addition to a mutation in VHL coding sequences) and in 1 large family with typical VHL disease but without any alteration in the other VHL exons. In this study, we show that the mutations induced a dysregulation of VHL splicing with excessive retention of E1' and were associated with a downregulation of VHL protein expression. In addition, we demonstrate a pathogenic role for synonymous mutations in VHL exon 2 that altered splicing through E2-skipping in 5 families with erythrocytosis or VHL disease. In all the studied cases, the mutations differentially affected splicing, correlating with phenotype severity. This study demonstrates that cryptic exon retention and exon skipping are new VHL alterations and reveals a novel complex splicing regulation of the VHL gene. These findings open new avenues for diagnosis and research regarding the VHL-related hypoxia-signaling pathway.


Assuntos
Éxons , Predisposição Genética para Doença , Mutação , Policitemia/genética , Processamento de RNA , Proteína Supressora de Tumor Von Hippel-Lindau/genética , Doença de von Hippel-Lindau/genética , Adolescente , Adulto , Criança , Feminino , Heterozigoto , Humanos , Masculino , Pessoa de Meia-Idade , Linhagem , Policitemia/classificação , Policitemia/patologia , Adulto Jovem , Doença de von Hippel-Lindau/patologia
19.
Hormones (Athens) ; 17(2): 153-166, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29858849

RESUMO

Thalassemia Major (TM) is a clinical entity with a high prevalence of low bone mass. The aim of the present study was to perform a meta-analysis of all available data on the role of bisphosphonates (BPs) in the therapy of thalassemia major-induced osteoporosis. The PRISMA recommendations for reporting systematic reviews and meta-analyses were used to guide the present study. We searched PubMed and the Cochrane Central Register of Controlled Trials (CENTRAL) through March 31, 2017 for articles related to thalassemia and BPs. To meta-analytically synthesize the primary endpoint, we used the standardized mean difference (SMD) after Hedges's g transformation under the scenario of a random effects model. Heterogeneity across studies was examined using the I2 statistic. Nine randomized controlled trials (RCTs) containing original data were included in this review. Three studies were performed in Italy, one in Australia, three in Greece, one in Cyprus, and one in China. The BPs investigated included zoledronate, alendronate, pamidronate, clodronate, and neridronate. Zoledronate and alendronate showed a tendency to perform best as compared to neridronate and the placebo effect with respect to femoral neck, lumbar spine, total hip, and total body in terms of bone mass density (g/cm2). BPs and in particular, zolendronate, were quite effective in the treatment of osteoporosis. These findings suggested that bisphosphonates are still a front-line treatment of osteoporosis in TM. However, to draw more meaningful and significant conclusions for the use and efficacy of BP in TM, larger and more complete RCTs should be conducted.


Assuntos
Conservadores da Densidade Óssea/farmacologia , Difosfonatos/farmacologia , Osteoporose/tratamento farmacológico , Talassemia/complicações , Humanos , Osteoporose/etiologia
20.
Eur J Haematol ; 101(3): 297-304, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29786897

RESUMO

BACKGROUND: Most patients with anemia are diagnosed through clinical phenotype and basic laboratory testing. Nonetheless, in cases of rare congenital anemias, some patients remain undiagnosed despite undergoing an exhaustive workup. Genetic testing is complicated by the large number of genes involved in rare anemias and the similarities in the clinical presentation of the different syndromes. OBJECTIVE: We aimed to enhance the diagnosis of patients with congenital anemias by using targeted next-generation sequencing. METHODS: Genetic diagnosis was performed by gene capture followed by next-generation sequencing of 76 genes known to cause anemia syndromes. RESULTS: Genetic diagnosis was achieved in 13 out of 21 patients (62%). Six patients were diagnosed with pyruvate kinase deficiency, 4 with dehydrated hereditary stomatocytosis, 2 with sideroblastic anemia, and 1 with CDA type IV. Eight novel mutations were found. In 7 patients, the genetic diagnosis differed from the pretest presumed diagnosis. The mean lag time from presentation to diagnosis was over 13 years. CONCLUSIONS: Targeted next-generation sequencing led to an accurate diagnosis in over 60% of patients with rare anemias. These patients do not need further diagnostic workup. Earlier incorporation of this method into the workup of patients with congenital anemia may improve patients' care and enable genetic counseling.


Assuntos
Anemia/congênito , Anemia/diagnóstico , Estudos de Associação Genética , Adolescente , Adulto , Anemia/sangue , Anemia/terapia , Anemia Diseritropoética Congênita/diagnóstico , Anemia Diseritropoética Congênita/genética , Anemia Diseritropoética Congênita/terapia , Anemia Hemolítica Congênita/diagnóstico , Anemia Hemolítica Congênita/genética , Anemia Hemolítica Congênita não Esferocítica/diagnóstico , Anemia Hemolítica Congênita não Esferocítica/genética , Anemia Sideroblástica/diagnóstico , Anemia Sideroblástica/genética , Medula Óssea/patologia , Criança , Pré-Escolar , Biologia Computacional , Índices de Eritrócitos , Feminino , Predisposição Genética para Doença , Testes Genéticos , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Hidropisia Fetal/diagnóstico , Hidropisia Fetal/genética , Masculino , Mutação , Piruvato Quinase/deficiência , Piruvato Quinase/genética , Erros Inatos do Metabolismo dos Piruvatos/diagnóstico , Erros Inatos do Metabolismo dos Piruvatos/genética , Doenças Raras , Adulto Jovem
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA