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1.
Expert Opin Drug Saf ; 19(2): 223-228, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31698959

RESUMO

Objectives: Recent studies have shown an increase risk of cardiovascular and hematological adverse events associated with vascular endothelial growth factor tyrosine kinase inhibitors (VEGF-TKIs). The authors hypothesize that the original studies may have produced exaggerated results because of the small baseline risks involved.Methods: A meta-analysis that included 71 trials, 8 different VEGFR-TKIs, and 11 adverse events were re-analyzed. The outcome of interest was re-defined as the complementary outcome (i.e. remaining free of an adverse event). The inverse variance heterogeneity model was used to pool the effect size.Results: VEGFR-TKIs decreased the risk of remaining free of hypertension by 7% (RR 0.93; 95%CI:0.88-0.97). Specific VEGFR-TKIs; pazopanib, regorafenib, and nintedanib were associated with a decrease risk of remaining free of an arterial thrombotic event (RR 0.96; 95%CI:0.93-0.99), thrombocytopenia (RR 0.91; 95%CI:0.89-0.93), and bleeding (RR 0.96; 95%CI:0.93-0.99) respectively. VEGFR-TKIs were not associated with the thrombotic event, myocardial infarction, stroke, venous thrombotic event, pulmonary embolism, left ventricular dysfunction, or QTc interval prolongation.Conclusion: VEGFR-TKIs are associated with a small increase in the risk of patients developing hypertension, arterial thrombotic events, thrombocytopenia, and bleeding. Previous studies overestimated the actual risk associated with VEGFR-TKIs by analyzing the outcome with the lower baseline risk.


Assuntos
Doenças Cardiovasculares/epidemiologia , Doenças Hematológicas/epidemiologia , Inibidores de Proteínas Quinases/efeitos adversos , Inibidores da Angiogênese/administração & dosagem , Inibidores da Angiogênese/efeitos adversos , Doenças Cardiovasculares/etiologia , Doenças Hematológicas/etiologia , Humanos , Inibidores de Proteínas Quinases/administração & dosagem , Receptores de Fatores de Crescimento do Endotélio Vascular/antagonistas & inibidores
2.
Zhongguo Fei Ai Za Zhi ; 22(10): 676-680, 2019 Oct 20.
Artigo em Chinês | MEDLINE | ID: mdl-31650953

RESUMO

Immune checkpoint inhibitors are able to reactivate the immune system therefore enhance the anti-tumor effects. However, over-activated T cells may induce immune related adverse events (irAEs). Hematological irAEs are rarely reported, which mainly represent as mono-lineage cytopenia or pancytopenia, including autoimmune hemolytic anemia (AIHA), immune thrombocytopenia (ITP), neutropenia and aplastic anemia, sometimes even lethal, such as hemophagocytic lymphohistiocytosis. The clinical manifestations of hematological irAEs will be summarized and recommendations of diagnosis and treatment are proposed.


Assuntos
Doenças Hematológicas/diagnóstico , Doenças Hematológicas/terapia , Imunoterapia/efeitos adversos , Doenças Hematológicas/etiologia , Humanos
3.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 27(5): 1672-1677, 2019 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-31607330

RESUMO

OBJECTIVE: To investigate the clinical characteristics, prevention and treatment of invasive fungal disease (IFD). METHODS: The clinical data of 164 patients who met the diagnostic criteria of IFD in our center from January 2012 to January 2015 were retrospectively analyzed. The incidence, clinical characteristics, related factors, treatment methods and prognosis were analyzed. RESULTS: Among 1289 cases of blood diseases, 164 cases suffered from IFD with inciduce of 12.7%. The main infection sites were as followed: lung, blood and gastrointestinal tract, with incidence of 84.2%, 5.5% and 3% respectively. The funge was found in 35 cases by detection; among fungi, the detected rate of candida albicans. aspergillus and candida glabrata was more high with 51.5%, 20% and 14.3% respectively. Among 164 childen with blood deseases complicated by IFD, 36 cases gained complete remission, 97 cases gained partial remission, 10 cases were stable, 11 cases were progressive and 10 cases died, the overall effective rate reached 81.1%. The univariate analysis showed that the gramulopenia, granulocyte recovery, long-term use of corticosteroid and immuno-suppressive agents, as well as different grades of diagnosis were significant factors affecting the efficacy of antifungal therapy for blood disease children with IFD, the multivariate analysis further showed that the granulocyte recovery and diagnosis grades were independent prognostic factors affecting the therapeutic efficacy for IFD children. The overall survival rate of IFD children with 12 weeks of antifungal treatnment was 81.7%, out of which the survival rate of IFD children at 12 weeks of treatment with itraconazole, voriconazole, amphotericin B and caspofungin was 81.4%, 80%, 69.4% and 97.1% respectively, there were significant differences in survival rate between each other by long rank test. In addition of caspofungin, the other 3 kinds of drugs had toxic side effects of different degrees, but IFD children could tolerated these effects after symptomatic treatment. CONCLUSION: The incidence of IFD in children with blood deseases in our hospital is 12.7%, the lung is most common infective site, moreover patogens of IFD mainly is candida. The promotion of granulocyte recovery and early stratified diagnosis can contribule to the treatment of IFD. For the IFD children with better economic condition, the caspofungin is a potent antifungal agent with high efficacy, low toxicity and better prognosis.


Assuntos
Doenças Hematológicas , Infecções Fúngicas Invasivas , Anfotericina B , Antifúngicos , Criança , Doenças Hematológicas/etiologia , Humanos , Infecções Fúngicas Invasivas/complicações , Estudos Retrospectivos
4.
Khirurgiia (Mosk) ; (9): 66-72, 2019.
Artigo em Russo | MEDLINE | ID: mdl-31532169

RESUMO

OBJECTIVE: The purpose of the study is to determine the correlation of changes in the humoral and tissue components of the hemostasis system with lipid metabolism in case of various urgent surgical diseases, on the basis of which the systemic coagulopathic distress syndrome can be used as the scientific basis for the definition of a new syndrome. MATERIAL AND METHODS: The work includes the results of experimental and clinical laboratory tests. Experiments on dogs: in the first group (n=18) destructive pancreatitis; in the second (n=18) - fecal peritonitis; in the third (n=15), acute obstructive intestinal obstruction; in the fourth (n=16) fecal peritonitis, in the postoperative period, Remaxol (15 ml/kg) was included in the therapy. The analysis of 55 patients with acute peritonitis, operated on for acute appendicitis, perforated gastric or duodenal ulcer, acute intestinal obstruction, acute destructive cholecystitis. In the study group (n=28), Remaxol is included in the postoperative therapy. The state of the humoral and tissue (in the experiment, the tissues of the liver, intestines, kidneys, heart, lungs, pancreas, in the clinic - tissues of the resected organs) components of the hemostasis system was evaluated, a number of lipid metabolism indicators were determined, etc. RESULTS: In the early periods of all investigated urgent diseases of the abdomen, pronounced changes in the system of both humoral and tissue components of the hemostasis system were revealed. The modification of the coagulation system is registered not only in the tissues of the lesion organs, but also in the target organs (system tissue hemocoagulation modifications). The research established one of the most important processes - the trigger of the hemostatic cascade reaction - is membrane-destabilizing (the source of tissue thromboplastin), which is determined by changes in the phospholipid composition of various organs tissues (involved in the pathological process or not in it). Changes in lipid metabolism are due to the activation of phospholipases and membrane lipid peroxidation in tissues. The factual material was the scientific basis for the establishment of a new syndrome. Systemic coagulopathic distress syndrome is a set of pathological processes of the body, the most important component of which is a violation of the phospholipid bilayer of blood cell membranes and organ cells due to oxidative and phospholipase induced phenomena, leading to a coagulopathic condition. It changes understanding of the prevention of thrombohemorrhagic complications, proving the effectiveness of complex therapy, including not only anticoagulants, but also drugs with membrane-stabilizing activity, in particular, Remaxol.


Assuntos
Transtornos da Coagulação Sanguínea/prevenção & controle , Doenças do Sistema Digestório/complicações , Infecções Intra-Abdominais/complicações , Substâncias Protetoras/administração & dosagem , Succinatos/administração & dosagem , Doença Aguda , Animais , Apendicite/complicações , Transtornos da Coagulação Sanguínea/etiologia , Transtornos da Coagulação Sanguínea/fisiopatologia , Colecistite Aguda/complicações , Doenças do Sistema Digestório/fisiopatologia , Cães , Doenças Hematológicas/etiologia , Doenças Hematológicas/fisiopatologia , Doenças Hematológicas/prevenção & controle , Hemostasia/fisiologia , Humanos , Obstrução Intestinal/complicações , Infecções Intra-Abdominais/fisiopatologia , Metabolismo dos Lipídeos/fisiologia , Pancreatite/complicações , Úlcera Péptica Perfurada/complicações , Peritonite/complicações , Síndrome
5.
PLoS Biol ; 17(9): e3000087, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31479440

RESUMO

Kabuki Syndrome patients have a spectrum of congenital disorders, including congenital heart defects, the primary determinant of mortality. Seventy percent of Kabuki Syndrome patients have mutations in the histone methyl-transferase KMT2D. However, the underlying mechanisms that drive these congenital disorders are unknown. Here, we generated and characterized zebrafish kmt2d null mutants that recapitulate the cardinal phenotypic features of Kabuki Syndrome, including microcephaly, palate defects, abnormal ear development, and cardiac defects. The cardiac phenotype consists of a previously unknown vasculogenesis defect that affects endocardium patterning and, consequently, heart ventricle lumen formation. Additionally, zebrafish kmt2d null mutants have angiogenesis defects depicted by abnormal aortic arch development, hyperactive ectopic blood vessel sprouting, and aberrant patterning of the brain vascular plexus. We demonstrate that zebrafish kmt2d null mutants have robust Notch signaling hyperactivation in endocardial and endothelial cells, including increased protein levels of the Notch transcription factor Rbpj. Our zebrafish Kabuki Syndrome model reveals a regulatory link between the Notch pathway and Kmt2d during endothelium and endocardium patterning and shows that pharmacological inhibition of Notch signaling rebalances Rbpj protein levels and rescues the cardiovascular phenotype by enhancing endothelial and endocardial cell proliferation and stabilizing endocardial patterning. Taken together, these findings demonstrate that Kmt2d regulates vasculogenesis and angiogenesis, provide evidence for interactions between Kmt2d and Notch signaling in Kabuki Syndrome, and suggest future directions for clinical research.


Assuntos
Anormalidades Múltiplas/etiologia , Face/anormalidades , Doenças Hematológicas/etiologia , Neovascularização Fisiológica/genética , Receptores Notch/metabolismo , Doenças Vestibulares/etiologia , Anormalidades Múltiplas/metabolismo , Animais , Modelos Animais de Doenças , Orelha Média/anormalidades , Células Endoteliais/metabolismo , Coração/embriologia , Cardiopatias Congênitas/genética , Doenças Hematológicas/metabolismo , Proteína de Ligação a Sequências Sinal de Recombinação J de Imunoglobina/metabolismo , Mutação , Palato/anormalidades , Fenótipo , Receptores Notch/antagonistas & inibidores , Doenças Vestibulares/metabolismo , Peixe-Zebra , Proteínas de Peixe-Zebra/metabolismo
6.
Chemotherapy ; 64(2): 105-109, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31390619

RESUMO

BACKGROUND: Dexrazoxane (DEX) is indicated as a cardioprotective agent for breast cancer patients receiving the anthracycline doxorubicin. Two meta-analyses in metastatic breast cancer reported an apparent increase in the severity of myelosuppression when DEX was used. So far, no data in soft-tissue sarcoma (STS) patients are available. METHODS: We retrospectively analyzed hematological toxicity data from 133 consecutive STS patients who received a chemotherapy regimen containing an anthracycline and ifosfamide (AI) in the perioperative or metastatic settings between January 2006 and December 2017. Of these, 46 received off-label DEX concurrently with the AI treatment. The differences between incidence of any of the explored outcomes were assessed according to the Fisher exact test. RESULTS: Compared with the non-DEX group, DEX treatment was associated with significantly higher rates of grade 3/4 hematological toxicities: leukopenia (56.5 vs. 28.7%; p = 0.0014), neutropenia (69.6 vs. 24.1%; p = 0.0001), febrile neutropenia (52.2 vs. 20.7%; p = 0.0004), anemia (41.3 vs. 28.7%; p = 0.1758), and thrombocytopenia (54.3 vs. 32.1%; p = 0.0159). Similarly, in the DEX group dose reductions were more frequent compared to the non-DEX group (39.1 vs. 19.5%; p = 0.0221). CONCLUSION: Adding DEX to AI in STS patients leads to higher rates of bone marrow suppression in all blood components, as well as to more frequent events of febrile neutropenia and dose reductions.


Assuntos
Antraciclinas/uso terapêutico , Antibióticos Antineoplásicos/uso terapêutico , Dexrazoxano/uso terapêutico , Substâncias Protetoras/uso terapêutico , Sarcoma/tratamento farmacológico , Adulto , Idoso , Antraciclinas/efeitos adversos , Antibióticos Antineoplásicos/efeitos adversos , Feminino , Doenças Hematológicas/etiologia , Doenças Hematológicas/prevenção & controle , Humanos , Masculino , Pessoa de Meia-Idade , Neutropenia/etiologia , Neutropenia/prevenção & controle , Estudos Retrospectivos , Sarcoma/patologia , Adulto Jovem
7.
Lancet Haematol ; 6(10): e521-e529, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31378662

RESUMO

BACKGROUND: Anti-B-cell maturation antigen (BCMA) chimeric antigen receptor (CAR) T-cell therapy has been shown to have activity in patients with relapsed or refractory multiple myeloma. Reports have suggested that a small subgroup of less differentiated myeloma clones express CD19 and anti-CD19 CAR T-cell therapy has shown activity in some of these patients. We aimed to assess the activity and safety of a combination of humanised anti-CD19 and anti-BCMA CAR T cells in patients with relapsed or refractory multiple myeloma. METHODS: We did a single-centre, single-arm, phase 2 trial at the Affiliated Hospital of Xuzhou Medical University in China. Patients were eligible if they were aged 18-69 years, had histologically confirmed multiple myeloma, a Karnofsky Performance Score of 50 points or more, and met the International Myeloma Working Group diagnostic criteria for relapsed or refractory disease. Fludarabine (three daily doses of 30mg/m2) and cyclophosphamide (one daily dose of 750 mg/m2) were used to deplete lymphocytes before infusion of humanised anti-CD19 CAR T cells (1 × 106 cells per kg) and murine anti-BCMA CAR T cells (1 × 106 cells per kg). The primary outcome was the proportion of patients who achieved an overall response. Responses were assessed according to the International Myeloma Working Group criteria. This study is registered with the Chinese Clinical Trial Registration Center, number ChiCTR-OIC-17011272. FINDINGS: From May 1, 2017, to Jan 20, 2019, 22 patients were enrolled and 21 received an infusion of CAR T cells and were evaluable for safety and activity analyses. At a median follow-up of 179 days (IQR 72-295), 20 (95%) of 21 patients had an overall response, including nine (43%) stringent complete responses, three (14%) complete responses, five (24%) very good partial responses, and three (14%) partial responses. The most common adverse events included cytokine release syndrome (19 [90%] of 21), including 18 patients (86%) with grade 1-2 cytokine release syndrome. The most common serious adverse events were haematological toxicities, which occurred in 20 (95%) of 21 patients. Common grade 3 or higher adverse events included neutropenia (18 [86%]), anaemia (13 [62%]), and thrombocytopenia (13 [62%]). One patient died due to cerebral hemorrhage, which was considered related to sustained thrombocytopenia. No deaths were judged to be treatment-related. INTERPRETATION: Our results confirm that combined infusion of humanised anti-CD19 and anti-BCMA CAR T cells is feasible in patients with relapsed or refractory multiple myeloma, and the preliminary activity observed warrants further investigation in randomised trials. This dual CAR-T cell combinations might be a promising treatment option for relapsed or refractory multiple myeloma. FUNDING: National Natural Science Foundation of China, Natural Science Foundation, Key Research and Development Plan of Jiangsu.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Antígenos CD19/imunologia , Antígeno de Maturação de Linfócitos B/imunologia , Mieloma Múltiplo/tratamento farmacológico , Adolescente , Adulto , Idoso , Anticorpos Monoclonais Humanizados/efeitos adversos , Ciclofosfamida/farmacologia , Feminino , Doenças Hematológicas/etiologia , Humanos , Linfócitos/citologia , Linfócitos/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/patologia , Recidiva , Índice de Gravidade de Doença , Resultado do Tratamento , Vidarabina/análogos & derivados , Vidarabina/farmacologia , Adulto Jovem
8.
Cien Saude Colet ; 24(7): 2569-2582, 2019 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-31340274

RESUMO

Exposure to pesticides by the rural population is increasing worldwide. Pesticides can induce the development of different diseases such as cancer and diseases of the central nervous system. This study analysed the clinical symptoms and haematological changes of a rural population in Conceição do Castelo, Espirito Santo, Brazil. For evaluation of symptomatology exposure to pesticides, 142 rural workers were interviewed. Of these, 22 workers were selected for haematological tests randomly as to evaluate haematological changes during the period of exposure to pesticides. Haematological analyses showed that erythrocytes, haemoglobin, haematocrit, mean corpuscular (VCM) volume, mean corpuscular haemoglobin (MCH), mean corpuscular haemoglobin concentration (MCHC) are in accordance with the reference intervals in haematology. Variations in the concentrations of rods and neutrophils indicates that exposure to pesticides increases the amount of those cells. Haematological disorders in rural workers exposed to pesticides can be correlated with reported symptoms. The results described in this study are relevant to the health public and reinforce the concern about the indiscriminate use of pesticides.


Assuntos
Doenças Hematológicas/epidemiologia , Exposição Ocupacional/efeitos adversos , Praguicidas/toxicidade , População Rural , Adolescente , Adulto , Brasil/epidemiologia , Índices de Eritrócitos , Feminino , Doenças Hematológicas/etiologia , Testes Hematológicos , Hemoglobinas/análise , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
9.
J Korean Med Sci ; 34(27): e185, 2019 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-31293110

RESUMO

BACKGROUND: The objective of this study was to identify the effects of mycophenolate mofetil (MMF) on non-renal manifestations in systemic lupus erythematosus (SLE). METHODS: The study population comprised 439 SLE patients from the Korean Lupus Network registry who were followed up annually and completed the baseline survey and two follow-up visits from 2014 to 2018. Disease activity, laboratory markers, and clinical manifestations including mucocutaneous lesions, arthritis, serositis, neurological disorders, and hematologic/immunologic abnormalities were assessed. All variables by group (MMF and non-MMF) effects with time (baseline, 1st follow-up, and 2nd follow-up) were analyzed by generalized estimation equation. RESULTS: Seventy-two patients were treated with MMF. There was significant difference in frequencies of malar rash, arthritis, renal disorder, and hematologic disorder between MMF and non-MMF groups in total SLE patients. In subgroup analysis of hematologic abnormalities in total patients, frequency of leukopenia was significantly different between the two groups during follow-up (P = 0.001), but frequencies of hemolytic anemia, lymphopenia, and thrombocytopenia were not. In addition, frequencies of leukopenia in patients without lupus nephritis were significantly decreased in MMF group compared to non-MMF group (P = 0.012). CONCLUSION: This study showed that MMF might be a beneficial treatment for hematologic abnormalities, especially leukopenia, in SLE.


Assuntos
Lúpus Eritematoso Sistêmico/tratamento farmacológico , Ácido Micofenólico/uso terapêutico , Adulto , Depressão/complicações , Depressão/diagnóstico , Exantema/etiologia , Feminino , Doenças Hematológicas/etiologia , Humanos , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/patologia , Masculino , Pessoa de Meia-Idade , Ácido Micofenólico/efeitos adversos , Qualidade de Vida , Sistema de Registros , República da Coreia
10.
Medicina (Kaunas) ; 55(7)2019 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-31311098

RESUMO

Celiac disease (CD) is a systemic autoimmune disease driven by gluten-ingestion in genetically predisposed individuals. Although it primarily affects the small bowel, CD can also involve other organs and manifest as an extraintestinal disease. Among the extraintestinal features of CD, hematologic ones are rather frequent and consist of anemia, thrombocytosis (thrombocytopenia also, but rare), thrombotic or hemorrhagic events, IgA deficiency, hyposplenism, and lymphoma. These hematologic alterations can be the sole manifestation of the disease and should prompt for CD testing in a suggestive clinical scenario. Recognition of these atypical, extraintestinal presentations, including hematologic ones, could represent a great opportunity to increase the diagnostic rate of CD, which is currently one of the most underdiagnosed chronic digestive disorders worldwide. In this review, we summarize recent evidence regarding the hematological manifestations of CD, with focus on practical recommendations for clinicians.


Assuntos
Doença Celíaca/complicações , Doenças Hematológicas/etiologia , Anemia/etiologia , Anemia/fisiopatologia , Doença Celíaca/fisiopatologia , Doenças Hematológicas/fisiopatologia , Humanos , Deficiência de IgA/etiologia , Deficiência de IgA/fisiopatologia , Linfoma/etiologia , Linfoma/fisiopatologia
11.
Med. intensiva (Madr., Ed. impr.) ; 43(5): 281-289, jun.-jul. 2019. graf, tab
Artigo em Espanhol | IBECS | ID: ibc-183240

RESUMO

Objetivos: Analizar las complicaciones hematológicas y las necesidades transfusionales en niños tratados con oxigenación por membrana extracorpórea (ECMO). Diseño: Estudio retrospectivo. Ámbito: Unidad de cuidados intensivos pediátricos. Pacientes: Niños menores de 18 años tratados con ECMO entre septiembre de 2006 y noviembre de 2015. Intervenciones: Ninguna. Variables de interés: Características clínicas, de la ECMO, anticoagulación, parámetros hematológicos y de coagulación, transfusiones y evolución clínica. Resultados: Se estudiaron 100 pacientes con una mediana de edad de 11 meses. Presentaron sangrado 76; el mediastino fue la localización más frecuente; 39 precisaron revisión quirúrgica. En los primeros 3 días de ECMO, el 97% de los pacientes precisaron transfusión de hematíes (34,4 ml/kg al día), el 94% plaquetas (21,1ml/kg al día) y el 90% plasma (26,6ml/kg al día). Los pacientes posquirúrgicos, con imposibilidad de salida de la circulación extracorpórea, los que presentaron sangrado al inicio de la ECMO, los que precisaron revisión quirúrgica y los que tuvieron canulación transtorácica requirieron mayor volumen de transfusiones. Se produjeron tromboembolias en 14 pacientes y hemólisis en 33. La mortalidad de los niños que presentaron sangrado al inicio de ECMO (57,6%) fue significativamente mayor que la del resto (37,5%) (p = 0,048). Conclusiones: Los niños tratados con ECMO presentan una elevada incidencia de sangrado y precisan un gran volumen de transfusiones. El postoperatorio de cirugía, el sangrado al inicio de la ECMO, la necesidad de revisión quirúrgica, la imposibilidad de salida de la circulación extracorpórea y la canulación transtorácica se asocian a un mayor volumen de transfusiones. Los niños que sangraron al inicio de la ECMO presentaron mayor mortalidad


Objectives: To analyze the hematological complications and need for transfusions in children receiving extracorporeal life support (ECLS). Design: A retrospective study was carried out. Setting: A pediatric intensive care unit. Patients: Children under 18 years of age subjected to ECLS between September 2006 and November 2015. Interventions: None. Variables of interest: Patient and ECLS characteristics, anticoagulation, hematological and coagulation parameters, transfusions and clinical course. Results: A total of 100 patients (94 with heart disease) with a median age of 11 months were studied. Seventy-six patients presented bleeding. The most frequent bleeding point was the mediastinum and 39 patients required revision surgery. In the first 3days, 97% of the patients required blood transfusion (34.4ml/kg per day), 94% platelets (21.1ml/kg per day) and 90% plasma (26.6ml/kg per day). Patients who were in the postoperative period, those who were bleeding at the start of ECLS, those requiring revision surgery, those who could not suspend extracorporeal circulation, and those subjected to transthoracic cannulation required a greater volume of transfusions than the rest of the patients. Thromboembolism occurred in 14 patients and hemolysis in 33 patients. Mortality among the children who were bleeding at the start of ECLS (57.6%) was significantly higher than in the rest of the patients (37.5%) (P=.048). Conclusions: Children subjected to ECLS present high blood product needs. The main factors related to transfusions were the postoperative period, bleeding at the start of ECLS, revision surgery, transthoracic cannulation, and the impossibility of suspending extracorporeal circulation. Children with bleeding suffered greater mortality than the rest of the patients


Assuntos
Humanos , Masculino , Feminino , Lactente , Pré-Escolar , Criança , Adolescente , Oxigenação por Membrana Extracorpórea/métodos , Transfusão de Sangue/tendências , Unidades de Terapia Intensiva Pediátrica , Doenças Hematológicas/sangue , Estudos Retrospectivos , Substitutos Sanguíneos/uso terapêutico , Tromboembolia/mortalidade , Mortalidade Infantil , Hemorragia/complicações , Anticoagulantes , Modelos Logísticos , Hemólise , Doenças Hematológicas/complicações , Doenças Hematológicas/etiologia
12.
Lancet Haematol ; 6(8): e419-e428, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31208944

RESUMO

BACKGROUND: Fludarabine, cyclophosphamide, and rituximab (FCR) can improve disease-free survival for younger (age ≤65 years) fit patients with chronic lymphocytic leukaemia with mutated IGHV. However, patients with unmutated IGHV rarely have durable responses. Ibrutinib is active for patients with chronic lymphocytic leukaemia irrespective of IGHV mutation status but requires continuous treatment. We postulated that time-limited ibrutinib plus FCR would induce durable responses in younger fit patients with chronic lymphocytic leukaemia. METHODS: We did a multicentre, open-label, non-randomised, single-arm phase 2 trial at seven sites in the USA. We enrolled patients aged 65 years or younger with previously untreated chronic lymphocytic leukaemia. Our initial cohort (original cohort) was not restricted by prognostic marker status and included patients who had del(17p) or TP53 aberrations. After a protocol amendment (on March 21, 2017), we enrolled an additional cohort (expansion cohort) that included patients without del(17p). Ibrutinib was given orally (420 mg/day) for 7 days, then up to six 28-day cycles were administered intravenously of fludarabine (25 mg/m2, days 1-3), cyclophosphamide (250 mg/m2, days 1-3), and rituximab (375 mg/m2 day 1 of cycle 1; 500 mg/m2 day 1 of cycles 2-6) with continuous oral ibrutinib (420 mg/day). Responders continued on ibrutinib maintenance for up to 2 years, and patients with undetectable minimal residual disease in bone marrow after 2 years were able to discontinue treatment. The primary endpoint was the proportion of patients who achieved a complete response with undetectable minimal residual disease in bone marrow 2 months after the last cycle of ibrutinib plus FCR. Analyses were done per-protocol in all patients who received at least one dose of study treatment. This trial is registered with ClinicalTrials.gov (NCT02251548) and is ongoing. FINDINGS: Between Oct 23, 2014, and April 23, 2018, 85 patients with chronic lymphocytic leukaemia were enrolled. del(17p) was detected in four (5%) of 83 patients and TP53 mutations were noted in three (4%) of 81 patients; two patients had both del(17p) and TP53 mutations. Median patients' age was 55 years (IQR 50-58). At data cutoff, median follow-up was 16·5 months (IQR 10·6-34·1). A complete response and undetectable minimal residual disease in bone marrow 2 months after the last cycle of ibrutinib plus FCR was achieved by 28 (33%, 95% CI 0·23-0·44) of 85 patients (p=0·0035 compared with a 20% historical value with FCR alone). A best response of undetectable minimal residual disease in bone marrow was achieved by 71 (84%) of 85 patients during the study. One patient had disease progression and one patient died (sudden cardiac death after 17 months of ibrutinib maintenance, assessed as possibly related to ibrutinib). The most common all-grade toxic effects were haematological, including thrombocytopenia in 63 (74%) patients, neutropenia in 53 (62%), and anaemia in 41 (49%). Grade 3 or 4 non-haematological serious adverse events included grade 3 atrial fibrillation in three (4%) patients and grade 3 Pneumocystis jirovecii pneumonia in two (2%). INTERPRETATION: The proportion of patients who achieved undetectable minimal residual disease in bone marrow with ibrutinib plus FCR is, to our knowledge, the highest ever published in patients with chronic lymphocytic leukaemia unrestricted by prognostic marker status. Ibrutinib plus FCR is promising as a time-limited combination regimen for frontline chronic lymphocytic leukaemia treatment in younger fit patients. FUNDING: Pharmacyclics and the Leukemia & Lymphoma Society.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Ciclofosfamida/administração & dosagem , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Inibidores de Proteínas Quinases/administração & dosagem , Pirazóis/administração & dosagem , Pirimidinas/administração & dosagem , Rituximab/administração & dosagem , Vidarabina/análogos & derivados , Administração Oral , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Ciclofosfamida/efeitos adversos , Esquema de Medicação , Feminino , Doenças Hematológicas/etiologia , Doenças Hematológicas/patologia , Humanos , Cadeias Pesadas de Imunoglobulinas/genética , Masculino , Pessoa de Meia-Idade , Mutação , Inibidores de Proteínas Quinases/efeitos adversos , Pirazóis/efeitos adversos , Pirimidinas/efeitos adversos , Indução de Remissão , Rituximab/efeitos adversos , Resultado do Tratamento , Proteína Supressora de Tumor p53/genética , Vidarabina/administração & dosagem , Vidarabina/efeitos adversos
13.
Nutr Clin Pract ; 34(4): 504-513, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31209935

RESUMO

BACKGROUND: The metabolism of the essential trace element copper remains incompletely understood and, until recently, nearly ignored in acute medicine. Menkes disease was for long the only known copper deficiency condition, but several case reports and investigations conducted over the last 2 decades have shown that deficiency is more frequent than previously suspected, with devastating individual consequences and potential public health consequences. The copper needs in healthy individuals are 0.9 mg/d, which translates to 0.3 mg/d intravenously in parenteral nutrition; the present review aims at gathering actual knowledge. METHOD AND RESULTS: A review of literature was conducted in PubMed and Cochrane systematic reviews to identify the most recent information about copper deficiency and generate a narrative review. Copper deficiency has hereditary and acquired origins, the latter being the most frequent. Clinical manifestations are nonspecific but affect all organs and systems, particularly the hematologic (anemia) and the neurologic (myeloneuropathy) systems. Deficiency also affects the cardiovascular, cutaneous, and immune systems. Severe copper deficiency due to reduced absorption after bariatric bypass surgery has become frequent. CONCLUSION: Deficiency is more frequent than previously recognized, probably because of changing nutrition patterns but also because of some treatments that have become very common such as bypass bariatric surgery and, in acute medicine, prolonged continuous renal replacement therapy. The patients may present with severe hematologic and neurologic complications that go untreated because copper deficiency was not considered in the differential diagnosis: These complications often need active intravenous repletion with doses 4-8 times the usual nutrition recommendations.


Assuntos
Cobre/deficiência , Doenças Hematológicas/etiologia , Doenças do Sistema Nervoso/etiologia , Oligoelementos/deficiência , Cirurgia Bariátrica/efeitos adversos , Humanos , Recomendações Nutricionais
14.
Chemotherapy ; 64(1): 42-47, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31163446

RESUMO

OBJECTIVES: We aimed to identify an optimal regimen for low-risk gestational trophoblastic neoplasia (LR-GTN) providing reduction in dosage and toxicity/side effects, enhancement of therapeutic efficacy, and a shorter treatment duration. METHODS: A total of 149 LR-GTN patients were enrolled in the affiliated Beijing Maternity Hospital of Capital Medical University from January 2014 to January 2017 and randomly divided into 3 groups with 50 cases in the methotrexate (MTX) group, 49 in actinomycin D (ACT-D) group, and 50 in ACT-D+MTX group. Follow-up recorded symptoms, physical and bimanual gynecological examinations, routine blood test, serum ß-HCG level, liver and renal functions, electrolytes, electrocardiogram before each treatment course, and pelvic and abdominal B-mode ultrasound or pelvic/abdominal/chest computed tomography. RESULTS: Serum complete remission (SCR) was 96.0, 87.8, and 83.7% for the ACT-D+MTX, ACT-D, and MTX groups, respectively, with SCR being highest in the ACT-D+MTX group, statistically higher than in the MTX group. Vomiting was the only side effect differing significantly by chemotherapy regimen, with a distinctly higher incidence in the ACT-D+MTX group compared with the MTX group (p = 0.028). The reduction rate of serum ß-HCG in the ACT-D+MTX group was significantly greater than in the other 2 groups. CONCLUSION: Combined ACT-D+MTX chemotherapy achieved overall better efficacy and showed less toxicity than ACT-D or MTX alone, and thus can be prioritized for the treatment of LR-GTN.


Assuntos
Antimetabólitos Antineoplásicos/uso terapêutico , Dactinomicina/uso terapêutico , Doença Trofoblástica Gestacional/tratamento farmacológico , Metotrexato/uso terapêutico , Adulto , Antimetabólitos Antineoplásicos/efeitos adversos , Gonadotropina Coriônica/sangue , Dactinomicina/efeitos adversos , Quimioterapia Combinada , Feminino , Doença Trofoblástica Gestacional/patologia , Doenças Hematológicas/etiologia , Humanos , Modelos Logísticos , Metotrexato/efeitos adversos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Úlceras Orais/etiologia , Gravidez , Prognóstico , Resultado do Tratamento , Adulto Jovem
15.
Bull Cancer ; 106(6): 590-603, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31072598

RESUMO

Paraneoplastic syndromes are signs or symptoms that result from tissue damage at locations remote from tumour sites. Paraneoplastic syndromes associated with cancer of unknown primary (CUP) are not well recognized as they are rarely reported. These syndromes can impair various organ functions and include endocrine, neurologic, dermatologic, rheumatologic, hematologic and several other system alterations. To our knowledge, the association between the histological CUP type and the paraneoplastic syndrome has never been assessed. In some instances, paraneoplastic syndromes can become the major clinical problems determining survival. However, they can also herald earlier the occurrence of CUP in patients with asymptomatic tumors. In this article, we review the available literature of CUP patients presenting paraneoplastic syndromes by trying to collect all available published cases during the last three decades. One additional goal of this article is to make practicing oncologists aware of the coexistence of paraneoplastic syndromes in patients with CUP.


Assuntos
Neoplasias Primárias Desconhecidas/complicações , Síndromes Paraneoplásicas/etiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Doenças Hematológicas/diagnóstico , Doenças Hematológicas/etiologia , Humanos , Masculino , Oncologia , Pessoa de Meia-Idade , Especificidade de Órgãos , Síndromes Endócrinas Paraneoplásicas/diagnóstico , Síndromes Endócrinas Paraneoplásicas/etiologia , Síndromes Paraneoplásicas/classificação , Síndromes Paraneoplásicas/diagnóstico , Síndromes Paraneoplásicas do Sistema Nervoso/diagnóstico , Síndromes Paraneoplásicas do Sistema Nervoso/etiologia , Doenças Reumáticas/diagnóstico , Doenças Reumáticas/etiologia , Dermatopatias/epidemiologia , Dermatopatias/etiologia
16.
Acta Haematol ; 141(2): 111-118, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30726834

RESUMO

We assessed the efficacy and safety of weekly cyclophosphamide-bortezomib-dexamethasone (CBD) induction prior to autologous stem cell transplantation (ASCT) in newly diagnosed Japanese patients with multiple myeloma (MM). This regimen consisted of four 28-day cycles of once-weekly oral cyclophosphamide (300 mg/m2), subcutaneous bortezomib (1.3 mg/m2), and oral dexamethasone (40 mg). Responding patients underwent stem cell collection followed by ASCT. The primary endpoint was the postinduction rate of achieving a near complete response (nCR) or better. Among the 38 enrolled patients, a complete response (CR), an nCR, a very good partial response (VGPR), and a partial response (PR) were achieved in 10.5, 2.6, 23.7, and 36.8% of cases, respectively. A grade 4 hematological adverse event (AE) was observed in 1 patient. Grade 3-4 infection, including febrile neutropenia, was observed in 4 patients (10.5%). Although 2 patients dropped out due to AE, 94.7% of the patients completed the induction phase. However, because of a poor response to induction chemotherapy (

Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bortezomib/administração & dosagem , Ciclofosfamida/administração & dosagem , Dexametasona/administração & dosagem , Mieloma Múltiplo/tratamento farmacológico , Adolescente , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Bortezomib/efeitos adversos , Ciclofosfamida/efeitos adversos , Dexametasona/efeitos adversos , Esquema de Medicação , Feminino , Doenças Hematológicas/etiologia , Transplante de Células-Tronco Hematopoéticas , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/diagnóstico , Mieloma Múltiplo/mortalidade , Análise de Sobrevida , Transplante Autólogo , Resultado do Tratamento , Adulto Jovem
17.
Rev Med Interne ; 40(4): 232-237, 2019 Apr.
Artigo em Francês | MEDLINE | ID: mdl-30773236

RESUMO

Many factors can contribute to the risk of venous thrombosis observed in hemolytic diseases. Some mechanisms are related to hemolysis by itself, while others seem more specific to each disease. Despite recent advances in the quantification of this risk and in understanding its physiopathology, the association of hemolysis with venous thrombosis is often unknown. The purpose of this general review is to clarify the main pro-thrombotic mechanisms during hemolysis and to synthesize the clinical data currently available. We will focus on the main types of hemolytic pathologies encountered in current practice, namely paroxysmal nocturnal hemoglobinuria, hemoglobinopathies, auto-immune hemolytic anemia and thrombotic microangiopathies.


Assuntos
Doenças Hematológicas , Hemólise/fisiologia , Anemia Hemolítica/sangue , Anemia Hemolítica/complicações , Anemia Hemolítica/diagnóstico , Doenças Hematológicas/sangue , Doenças Hematológicas/classificação , Doenças Hematológicas/diagnóstico , Doenças Hematológicas/etiologia , Humanos , Fatores de Risco , Trombose/complicações , Trombose/diagnóstico , Trombose Venosa/diagnóstico , Trombose Venosa/etiologia
18.
J Eur Acad Dermatol Venereol ; 33(4): 774-780, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30633418

RESUMO

BACKGROUND: Hair and scalp involvement in systemic lupus erythematosus (SLE) can manifest as scarring alopecia, non-scarring alopecia or scalp/hair shaft changes without apparent hair loss. While trichoscopic signs in chronic cutaneous lupus are well established, data on SLE patients with normal-looking or non-scarring scalp are limited. OBJECTIVES: To investigate trichoscopic features of SLE patients without chronic cutaneous scalp lesions and compare the findings with normal controls, as well as determine which feature associates with systemic disease. Furthermore, we aim to explore different clinical presentations of the scalp in SLE patients and their association with disease activity. METHODS: Trichoscopic photographs were taken from patients and healthy controls and evaluated by one blinded hair specialist. For SLE patients, their clinical presentations and evaluations for cutaneous, extracutaneous involvement; SLE Activity Index 2000 (SLEDAI-2K) score were documented. RESULTS: Of 109 SLE patients and 305 healthy controls were included. Hair shaft changes were significantly more common in SLE and associated with higher SLEDAI-2K (P < 0.05). The most common feature was prominent arborizing blood vessels (60.6% vs. 18.4%, P < 0.001), followed by thick arborizing blood vessels (57.8% vs. 10.2%, P < 0.001), black dots (47.7% vs. 2%, P < 0.001), brown scattered pigmentation (5.5% vs. 0.7%, P = 0.005) and blue-grey speckled pigmentation (44% vs.0.3%, P < 0.001). When hair loss is diffuse and severe, there were associations with haematologic (P = 0.002) and renal involvement (P = 0.027 for proteinuria > 500 mg/day, P = 0.004 for proteinuria > 1 g/day). CONCLUSIONS: Trichoscopic examination is a valuable tool for SLE diagnosis and monitoring. Severe diffuse non-scarring alopecia most likely indicates active disease.


Assuntos
Alopecia/diagnóstico por imagem , Dermoscopia , Cabelo/diagnóstico por imagem , Lúpus Eritematoso Sistêmico/diagnóstico por imagem , Couro Cabeludo/diagnóstico por imagem , Adulto , Alopecia/etiologia , Estudos de Casos e Controles , Estudos Transversais , Feminino , Doenças Hematológicas/etiologia , Humanos , Nefropatias/etiologia , Lúpus Eritematoso Sistêmico/complicações , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Método Simples-Cego , Adulto Jovem
19.
J Pediatr Hematol Oncol ; 41(3): e182-e185, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30339653

RESUMO

Nutritional deficiencies, including deficiencies of vitamin B12, copper, and vitamin C, may result in cytopenias and hematologic symptoms. Early recognition of these deficiencies is imperative for prompt treatment and improvement in hematologic and other manifestations. We describe 5 cases which illustrate the hematologic manifestations of nutritional deficiencies and challenges to initial diagnosis and management. Supplementation of the deficient vitamin or micronutrient in all of these cases resulted in rapid resolution of cytopenias, hemorrhage, and other associated hematologic symptoms. We also review other nutritional deficiencies that manifest with hematologic symptoms and compile recommendations on treatment and expected time to response.


Assuntos
Desnutrição/diagnóstico , Suplementos Nutricionais , Diagnóstico Precoce , Doenças Hematológicas/etiologia , Doenças Hematológicas/prevenção & controle , Doenças Hematológicas/terapia , Hemorragia/etiologia , Hemorragia/prevenção & controle , Hemorragia/terapia , Humanos , Desnutrição/complicações , Desnutrição/terapia , Pancitopenia/etiologia , Pancitopenia/prevenção & controle , Pancitopenia/terapia , Medicina Preventiva/métodos
20.
Am J Hematol ; 94(1): 29-38, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30264864

RESUMO

Eliglustat is a first-line oral therapy for adults with Gaucher disease type 1 (GD1) and poor, intermediate or extensive CYP2D6-metabolizer phenotypes (>90% of patients). We report the final results of a Phase 2 trial and extension (NCT00358150) in previously untreated adult GD1 patients who had splenomegaly with thrombocytopenia and/or anemia and received 50 or 100 mg eliglustat tartrate (equivalent to 42 or 84 mg eliglustat) twice daily for 8 years. In total, 19 of 26 patients completed the trial. After 8 years of eliglustat, mean spleen and liver volumes decreased by 69% and 34%, respectively. Mean hemoglobin concentration and platelet count increased by 2.2 g/dL and 113%, respectively. All patients met at least 3 of 4 therapeutic goals established for patients on long-term enzyme replacement therapy. Mean final values for patients with severe splenomegaly (n = 6), moderate-to-severe anemia (n = 6), or severe thrombocytopenia (n = 8) were similar to patients with milder disease at baseline and within long-term therapeutic goal thresholds. Biomarker median percent changes from baseline were -91% for chitotriosidase, -87% for CCL18, -92% for glucosylsphingosine, and -80% for plasma glucosylceramide. Mean lumbar spine T-score increased by 0.96, moving from the osteopenic to the normal range. Mean quality-of-life scores, mostly below normal at baseline, moved into ranges seen in healthy adults. Eliglustat was well-tolerated; 98% of adverse events were mild or moderate and 94% were considered unrelated to treatment. Clinically meaningful improvements in all parameters continued or were maintained over 8 years, with the largest margins of improvement seen in the most severely affected patients.


Assuntos
Inibidores Enzimáticos/uso terapêutico , Doença de Gaucher/tratamento farmacológico , Glucosiltransferases/antagonistas & inibidores , Pirrolidinas/uso terapêutico , Adulto , Densidade Óssea , Doenças Ósseas Metabólicas/tratamento farmacológico , Doenças Ósseas Metabólicas/etiologia , Feminino , Seguimentos , Doença de Gaucher/sangue , Doença de Gaucher/complicações , Glucosilceramidase/deficiência , Doenças Hematológicas/sangue , Doenças Hematológicas/tratamento farmacológico , Doenças Hematológicas/etiologia , Hemoglobinas/análise , Hepatomegalia/tratamento farmacológico , Hepatomegalia/etiologia , Hepatomegalia/patologia , Humanos , Fígado/efeitos dos fármacos , Fígado/patologia , Masculino , Contagem de Plaquetas , Baço/efeitos dos fármacos , Baço/patologia , Esplenomegalia/tratamento farmacológico , Esplenomegalia/etiologia , Esplenomegalia/patologia , Resultado do Tratamento
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