RESUMO
GATA2 mutations have been identified in various diseases, such as MonoMAC syndrome, Emberger syndrome, familial myelodysplastic syndrome, acute myeloid leukaemia and dendritic cell, monocyte, B-cell and natural killer-cell deficiency. These syndromes present a wide range of clinical features, dominated by severe infections and haematological disorders such as myelodysplastic syndrome. Up to 70% of patients with GATA2 mutations have dermatological features, mainly genital or extragenital warts, panniculitis or erythema nodosum and lymphoedema. We report three patients presenting with common dermatological and haematological features leading to the diagnosis of GATA2 deficiency, but also with skin manifestations that have not been previously described: gingival hypertrophy, macroglossitis and glossitis and granulomatous lupoid facial lesions. Dermatologists can encounter patients with GATA2 mutations and should recognize this disorder.
Assuntos
Deficiência de GATA2/complicações , Fator de Transcrição GATA2/genética , Mutação/genética , Dermatopatias/genética , Adulto , Criança , Eritema Nodoso/genética , Dermatoses Faciais/genética , Feminino , Deficiência de GATA2/diagnóstico , Hipertrofia Gengival/genética , Glossite/genética , Humanos , Lúpus Eritematoso Cutâneo/genética , Linfedema/genética , Masculino , Adulto JovemRESUMO
PURPOSE: Posaconazole is a triazole antifungal widely used for prophylaxis of invasive fungal disease (IFI). Posaconazole tablets allow reaching higher plasma levels than the oral suspension, but safety data with this formulation in real life are scarce. This study aimed at evaluating the safety profile, the pharmacokinetic variability, and the concentration-toxicity relationship of posaconazole tablets in patients with haematological malignancies. METHODS: Sixty neutropenic patients treated with posaconazole tablets for prophylaxis of IFI were prospectively included in the study. Adverse drug reactions (ADR) were recorded and analyzed by the Regional Pharmacovigilance Centre to assess posaconazole implication. Blood samples were drawn once a week and plasma trough concentrations (C min) were assayed by LC-MS/MS. The rates of ADR by quartile of C min were compared. RESULTS: Eighteen patients (30%) experienced at least one ADR attributed to posaconazole. Liver function test (LFT) abnormalities were encountered in 20% of patients and resulted in four (6.7%) treatment discontinuations. Posaconazole median (range) C min was 1.36 (< 0.1-3.44) µg/mL (inter-patient CV = 43.9%). During follow-up, 28.6% of patients had at least one concentration < 0.7 µg/mL, and 35.7% had at least one concentration > 2 µg/mL. Rates of ADR by quartile of C min were not different. CONCLUSIONS: Posaconazole was well tolerated; however, LFT abnormalities were frequent. ADR occurrence was not linked to posaconazole exposure. Because posaconazole concentrations were highly variable, TDM can be helpful to avoid underexposure to the drug and increase its efficacy in preventing IFI. Conversely, a large proportion of patients was overexposed and might have benefited of a dose reduction.
Assuntos
Triazóis/administração & dosagem , Triazóis/efeitos adversos , Administração Oral , Adulto , Idoso , Antifúngicos/administração & dosagem , Antifúngicos/efeitos adversos , Antifúngicos/farmacocinética , Monitoramento de Medicamentos/métodos , Feminino , Neoplasias Hematológicas/sangue , Neoplasias Hematológicas/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Comprimidos , Triazóis/sangue , Triazóis/farmacocinética , Adulto JovemRESUMO
Posaconazole is extensively used for prophylaxis for invasive fungal infections. The gastro-resistant tablet formulation has allowed the bioavailability issues encountered with the oral suspension to be overcome. However, overexposure is now frequent. This study aimed to (i) describe the pharmacokinetics of posaconazole tablets in a real-life cohort of patients with hematological malignancies and (ii) perform Monte Carlo simulations to assess the possibility that the daily dose can be reduced while keeping a sufficient exposure. Forty-nine consecutive inpatients were prospectively included in the study. Posaconazole trough concentrations (TC) were measured once a week, and biological and demographic data were collected. The concentrations were analyzed by compartmental modeling, and Monte Carlo simulations were performed using estimated parameters to assess the rate of attainment of the target TC after dose reduction. The pharmacokinetics of posaconazole were well described using a one-compartment model with first-order absorption and elimination. The values of the parameters (interindividual variabilities) were as follows: the absorption constant (ka ) was 0.588 h-1 (fixed), the volume of distribution (V/F) was 420 liters (28.2%), and clearance (CL/F) was 7.3 liters/h (24.2%) with 31.9% interoccasion variability. Forty-nine percent of the simulated patients had TC at steady state of ≥1.5 µg/ml and maintained a TC above 1 µg/ml after a reduction of the dose to 200 mg daily. A third of these patients eligible for a dose reduction had TC of ≥1.5 µg/ml as soon as 48 h of treatment. Though posaconazole tablets were less impacted by bioavailability issues than the oral suspension, the pharmacokinetics of posaconazole tablets remain highly variable. Simulations showed that approximately half of the patients would benefit from a reduction of the dose from 300 mg to 200 mg while keeping the TC above the minimal recommended target of 0.7 µg/ml, resulting in a 33% savings in the cost of this very expensive drug.
Assuntos
Antifúngicos/administração & dosagem , Antifúngicos/farmacocinética , Infecções Fúngicas Invasivas/prevenção & controle , Triazóis/administração & dosagem , Triazóis/farmacocinética , Administração Oral , Adulto , Idoso , Feminino , Neoplasias Hematológicas/complicações , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Biológicos , Método de Monte Carlo , Estudos Prospectivos , Comprimidos/administração & dosagemRESUMO
We assessed the benefit of predeposite autologous blood donation (PAD) before bone marrow (BM) donation on transfusion requirements, haemoglobin concentrations (Hb) and the occurrence of adverse events (AE). We collected data retrospectively from 50 donors of BM with PAD from 2010 to 2014. An autologous transfusion (AT) was given to 50% of the donors (group 1). In the group 2, the products from PAD were not used. The total volume median of marrow harvested was 17.7 mL/k (range 12.3-21.4) in the group 1 and 13.3 mL/k (8.6-22.6) in the group 2. The female ratio was higher in the group 1 (60%) than in the group 2 (16%). Bone marrow harvest led to a decline in Hb (from PAD to first day after BM donation) by 2.9 g/dL (1.5-5.5) in the group 1 and by 3.5 g/dL (1.2-5) in the group 2. The post-harvest Hb (D+1) median was identical in the two groups: 10.9 g/dL (7.6-13.5) in the group 1 versus 11.5 g/dL (9.3-13.4) in the group 2. Six AE were reported in each group. In the group with AE, the median weight was lower: 58 k (50-71) versus 75 k (52-110); and the median total volume of marrow harvested was higher: 20.1 mL/k (9.9-21.4) versus 14.3 mL/k (8.6-22.6). All post-harvest Hb were ≥ 7.6g/dL. This study shows the high loss of Hb after BM donation but not enough to prove a blood transfusion in BM donors with median age of 36 years (16-62) and without comorbidity. The occurrence of AE (25% of BM donors) justifies a careful surveillance after the BM donation. The PAD should not be routinely offered to bone marrow donors.
Assuntos
Doadores de Sangue , Transfusão de Sangue Autóloga/métodos , Transplante de Medula Óssea/métodos , Adolescente , Adulto , Transfusão de Sangue Autóloga/efeitos adversos , Transfusão de Sangue Autóloga/estatística & dados numéricos , Transplante de Medula Óssea/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto JovemRESUMO
UNLABELLED: Brittany is a low prevalence region for hemoglobinopathies. Despite of that, the number of patients is increasing each year. In 2013, 140 patients were known at the EFS Bretagne, and medical consultations are growing for 50% each year since 2011. The consequence is an increase of needs of 22% of compatible packed red blood cells. To anticipate the announced progress, various actions were implemented as study groups, creation of a new informatic prescription for red blood cells phenotyping, promotion of donation, transfusion organisation. RESULTS: Fifthty-nine percent of the 400 ABO RH-KELL, FY, JK, MNS 3, 4, red blood cells were realised on the basis of this new informatic prescription, as the 99% of the packed red blood cells identified Fy (a- b-). So, 92% of the compatible transfused packed red blood cells were already in stock when the patients needed them. CONCLUSIONS: In Brittany, that organisation leads to assume qualitative and quantitative transfusion for sickle cell disease in more than 90% of cases, with fast distribution. In the same time promotion of donation is done to increase the diversity of donors.
Assuntos
Transfusão de Eritrócitos , Necessidades e Demandas de Serviços de Saúde/organização & administração , Hemoglobinopatias/terapia , Estudos Transversais , França , HumanosRESUMO
BACKGROUND: Invasive aspergillosis is an opportunistic infection that occurs mainly among patients with prolonged neutropenia. Few data are available on invasive aspergillosis in nonneutropenic patients. METHODS: The aim of this survey was to compare neutropenic and nonneutropenic patients who had received a diagnosis of invasive aspergillosis at our institution during a 6-year period. RESULTS: Among the 88 cases of invasive aspergillosis analyzed here, 12 were histologically proven, 52 were probable, and 24 were possible. Forty-seven percent of cases were diagnosed in the intensive care unit, and 40% were diagnosed in hematology units. Neutropenia was a risk factor for 52 patients (59%), most of whom had hematological or solid malignancies. Among the 36 nonneutropenic patients (41%), the main underlying conditions were steroid-treated chronic obstructive pulmonary disease, asthma, rheumatoid arthritis, giant-cell arteritis, and microvascular disorders; 10 patients were recipients of solid-organ transplants, and 1 patient was seropositive for human immunodeficiency virus. The distribution of proven and probable invasive aspergillosis was similar for neutropenic and nonneutropenic patients. The mortality rate was 71.5% overall and was significantly higher among nonneutropenic patients than among neutropenic patients (89% vs. 60%; P<.05). Compared with neutropenic patients, nonneutropenic patients were significantly less likely to have symptoms of invasive aspergillosis and more likely to have frequent intercurrent pneumonia due to another microorganism. The sensitivity of mycological examination of bronchoalveolar lavage fluid specimens was higher for nonneutropenic patients than for neutropenic patients (85% vs. 58%; P<.05), whereas the sensitivity of antigenemia was the same for the 2 populations (65% vs. 64%). Findings on thoracic computed tomographs were similar, except that segmental areas of consolidation occurred more frequently among neutropenic patients. CONCLUSION: This survey at a whole institution underlines the high number of cases of invasive aspergillosis among nonneutropenic patients, with an overall mortality rate that was significantly higher than that for neutropenic patients.
Assuntos
Aspergilose/epidemiologia , Aspergilose/patologia , Neutropenia/complicações , Adolescente , Adulto , Idoso , Anticorpos Antifúngicos/sangue , Antifúngicos/uso terapêutico , Antígenos de Fungos/sangue , Aspergilose/complicações , Aspergilose/tratamento farmacológico , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Fatores de TempoAssuntos
Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Leucemia Mieloide/terapia , Doença Aguda , Idoso , Antígenos CD/metabolismo , Medula Óssea/patologia , Feminino , Fator Estimulador de Colônias de Granulócitos/administração & dosagem , Hemoglobinas/análise , Humanos , Contagem de Leucócitos , Indução de RemissãoRESUMO
In order to compare the nutritional status of tuberculosis (TB) patients who were human immunodeficiency virus (HIV)-seropositive with those who were seronegative, we carried out a cross-sectional anthropometric and biochemical assessment, together with bioelectrical impedance analysis (BIA) of the nutritional status of TB patients hospitalized in the Department of Internal Medicine, Bujumbura University Hospital, Burundi, East Africa. Of the 65 TB patients (33 pulmonary, 6 extrapulmonary, and 26 disseminated TB), 50 (76.9%) were HIV-seropositive (HIV+). When assessed according to anthropometric, BIA, and biochemical variables, HIV+ TB patients had more pronounced malnutrition than HIV- patients. Similar results were obtained when the comparison was restricted to patients with only pulmonary TB: HIV+ patients were more malnourished than HIV- patients. The results according to anthropometric measurements were: weight loss (13.5% of HIV- patients versus 26.4% of HIV+ patients, P = 0.005), body mass index (18.6 versus 15.1, P = 0.003), fat free mass (FFM) (13.9 versus 11.9, P < 0.01), and body fat (BF) (4.55 versus 3.71, P = 0.03) expressed per unit height2. BIA showed that the difference in FFM between HIV- and HIV+ TB pulmonary patients was mostly due to a decrease in body cellular mass. Measurements of albumin, prealbumin, and transferrin showed a marked decrease in all three markers in HIV+ TB pulmonary patients. The nutritional status of HIV+ patients with disseminated versus pulmonary TB was similar. The nutritional status of HIV+ TB patients is far worse than that of HIV- TB patients. In such patients, anthropometry underestimates the degree of malnutrition because it does not account for the water component of FFM. Nutritional status should be assessed and nutritional intervention should be provided in an attempt to improve the prognosis of TB patients, especially those who are infected by HIV.
Assuntos
Soropositividade para HIV/complicações , Distúrbios Nutricionais/complicações , Estado Nutricional , Tuberculose/complicações , Adolescente , Adulto , Idoso , Composição Corporal , Burundi , Estudos Transversais , Impedância Elétrica , Feminino , Soronegatividade para HIV , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
To determine the types of pulmonary disease associated with human immunodeficiency virus (HIV) infection, we conducted a prospective study of 302 consecutive patients admitted for acute respiratory disease to a university hospital in Bujumbura, Burundi. Diagnoses were made according to well-defined criteria. Of the total, 222 patients (73.5%) were HIV seropositive, with women younger than men. Features suggestive of underlying HIV infection were the clinical findings of oral thrush, peripheral lymphadenopathy, or herpes zoster and the radiographic abnormalities of hilar-mediastinal adenopathy or a reticulonodular infiltrate. Tuberculosis and community-acquired pneumonia occurred with approximately equal frequency in the HIV-seropositive and seronegative groups. Pneumocystis carinii pneumonia was diagnosed in 11 patients, all seropositive. Gram-negative bacteremia, especially Salmonella typhimurium, occurred in 23 seropositive patients (10.4%). A total of 24 seropositive patients died during the initial hospitalization, and 11 others required readmission; no seronegative patients died or were rehospitalized. We conclude that HIV infection is a major risk factor for the development of acute respiratory diseases in adults of sufficient severity to require hospitalization in Bujumbura. In this Central African country, where exposure to virulent bacterial pathogens is ubiquitous, tuberculosis, pneumonia, and salmonellosis occur with much greater frequency than classic AIDS-defining opportunistic infections or malignancies.