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1.
Hua Xi Kou Qiang Yi Xue Za Zhi ; 38(4): 454-459, 2020 Aug 01.
Artigo em Chinês | MEDLINE | ID: mdl-32865368

RESUMO

Severe congenital neutropenia is a rare disorder characterized by a consistently low absolute neutrophil count and periodontal disease. This report describes the case of an ELANE mutationin a patient with gingival bleeding and tooth mobility. Oral examination showed active periodontal infection of the primary dentition accompanied by alveolar bone loss in the posterior region. The patient was diagnosed with severe congenital neutropenia 1 year after multidisciplinary consultation. Treatment of the systemic disease and effective oral health education over a 3-year follow-up period relieved the periodontal infection and created favorable conditions for future repair.


Assuntos
Síndrome Congênita de Insuficiência da Medula Óssea , Neutropenia , Doenças Periodontais , Humanos , Mutação , Neutropenia/congênito
2.
Lancet Haematol ; 7(9): e649-e659, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32758434

RESUMO

BACKGROUND: Avadomide (CC-122) is a novel oral cereblon-modulating agent with promising activity in non-Hodgkin lymphoma. We aimed to examine the safety and preliminary activity of avadomide plus obinutuzumab in patients with relapsed or refractory non-Hodgkin lymphoma. METHODS: CC-122-NHL-001 was a phase 1b dose escalation and expansion study at eight sites in France, Italy, and the Netherlands. Eligible patients (aged ≥18 years) had histologically confirmed CD20-positive relapsed or refractory non-Hodgkin lymphoma, had an Eastern Cooperative Oncology Group performance status of 0 or 1, and had received previous treatment. In the dose expansion phase, only patients with previously treated relapsed or refractory follicular lymphoma (grade 1, 2, or 3a) were included. Avadomide was administered in escalating doses and two formulations: active pharmaceutical ingredient in capsule in 1·0 mg, 2·0 mg, 3·0 mg, and 4·0 mg doses and as formulated capsules in 3·0 mg and 4·0 mg doses orally once daily on days 1-5 followed by 2 days off (5-7-day schedule) every week of each 28-day cycle. Obinutuzumab 1000 mg was administered intravenously on days 2, 8, and 15 of cycle 1 and day 1 of cycles 2-8. Primary objectives were to determine the safety and tolerability, the non-tolerated dose, maximum tolerated dose, and recommended phase 2 dose (RP2D). All patients who received treatment were included in the safety analyses. Efficacy-evaluable patients completed at least one cycle of treatment and had baseline and at least one post-baseline assessment. The study is registered with ClinicalTrials.gov, NCT02417285 and EudraCT 2014-003333-26, and is ongoing. FINDINGS: Between June 24, 2015, and Dec 5, 2018, 73 patients were enrolled and treated; 19 had diffuse large B-cell lymphoma, 53 follicular lymphoma, and one marginal zone lymphoma. Median follow-up was 253 days (IQR 127-448). The median number of previous anticancer regimens was three (IQR 2-4). The maximum tolerated dose and non-tolerated dose were not reached in the dose escalation phase. On the basis of safety and pharmacokinetic-pharmacodynamic data, the avadomide RP2D was established as 3·0 mg as formulated capsules on a 5-7-day schedule in combination with 1000 mg of obinutuzumab. Patients enrolled in the expansion cohort received the established RP2D of avadomide. Across all doses, three patients had dose-limiting toxicities; one patient treated at the RP2D had dose-limiting toxicity (grade 3 sepsis). The most common adverse events of grade 3 and above were neutropenia (41 [56%] of 73) and thrombocytopenia (17 [23%] of 73). 34 (47%) patients had serious adverse events, which were considered to be avadomide-related in 23 (32%) of 73 patients and obinutuzumab-related in 20 (27%) of 73 patients. Two treatment-related deaths occurred, one owing to tumour flare and one from acute myeloid leukaemia after study discontinuation. INTERPRETATION: Avadomide plus obinutuzumab has a manageable toxicity, being a tolerable treatment option for most patients. Although the prespecified threshold for activity was not met in the trial, we believe that the preliminary antitumour activity of cereblon modulators plus next-generation anti-CD20 antibodies in heavily pretreated relapsed or refractory non-Hodgkin lymphoma warrants further investigation as a chemotherapy-free option in this setting. FUNDING: Celgene Corporation.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Piperidonas/uso terapêutico , Quinazolinonas/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Humanizados/efeitos adversos , Anticorpos Monoclonais Humanizados/farmacocinética , Antineoplásicos/uso terapêutico , Esquema de Medicação , Quimioterapia Combinada , Feminino , Meia-Vida , Humanos , Linfoma Difuso de Grandes Células B/patologia , Masculino , Pessoa de Meia-Idade , Neutropenia/etiologia , Neutropenia/patologia , Piperidonas/efeitos adversos , Piperidonas/farmacocinética , Quinazolinonas/efeitos adversos , Quinazolinonas/farmacocinética , Recidiva , Índice de Gravidade de Doença , Trombocitopenia/etiologia , Trombocitopenia/patologia , Resultado do Tratamento
3.
Rev Chilena Infectol ; 37(1): 77-81, 2020 Feb.
Artigo em Espanhol | MEDLINE | ID: mdl-32730404

RESUMO

The episodes of febrile neutropenia are severe cases that require an exhaustive etiological study and a quick start of antimicrobial agents. Within the possible microorganisms, fungal origins are also found, and depending on its tissue invasion, they can reach a high mortality rate. A case of a pediatric patient who suffered from acute myeloid leukemia is reported, and after his induction chemotherapy, the patient showed an episode of febrile neutropenia, which matches a rhinosinusal infection caused by Exserohilum rostratum, a filamentous fungi that is uncommonly associated with pathological cases. An antifungal therapy and an early surgical treatment were started, which lead to a positive response, without complications to the patient. After the monitoring and receiving secondary prophylaxis during the episodes of neutropenia, the patient hasn't presented new injuries nor rhinosinusal damage.


Assuntos
Antifúngicos , Ascomicetos , Leucemia Mieloide Aguda , Micoses , Sinusite , Antifúngicos/uso terapêutico , Ascomicetos/isolamento & purificação , Criança , Humanos , Leucemia Mieloide Aguda/complicações , Micoses/complicações , Micoses/tratamento farmacológico , Neutropenia/etiologia , Sinusite/complicações , Sinusite/tratamento farmacológico , Sinusite/microbiologia , Resultado do Tratamento
4.
BMC Infect Dis ; 20(1): 535, 2020 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-32703183

RESUMO

BACKGROUND: Breakthrough invasive fungal infections (bIFIs) are an area of concern in the scarcity of new antifungals. The mixed form of bIFIs is a rare phenomenon but could be potentially a troublesome challenge when caused by azole-resistant strains or non-Aspergillus fumigatus. To raise awareness and emphasize diagnostic challenges, we present a case of mixed bIFIs in a child with acute lymphoblastic leukemia. CASE PRESENTATION: A newly diagnosed 18-month-old boy with acute lymphoblastic leukemia was complicated with prolonged severe neutropenia after induction chemotherapy. He experienced repeated episodes of fever due to extended-spectrum beta-lactamase-producing Escherichia coli bloodstream infection and pulmonary invasive fungal infection with Aspergillus fumigatus (early-type bIFIs) while receiving antifungal prophylaxis. Shortly after pulmonary involvement, his condition aggravated by abnormal focal movement, loss of consciousness and seizure. Cerebral aspergillosis with Aspergillus niger diagnosed after brain tissue biopsy. The patient finally died despite 108-day antifungal therapy. CONCLUSIONS: Mixed bIFIs is a rare condition with high morbidity and mortality in the patients receiving immunosuppressants for hematological malignancies. This case highlights the clinical importance of Aspergillus identification at the species level in invasive fungal infections with multiple site involvement in the patients on antifungal prophylaxis.


Assuntos
Antifúngicos/uso terapêutico , Aspergillus fumigatus/imunologia , Aspergillus niger/genética , Coinfecção/diagnóstico , Aspergilose Pulmonar Invasiva/diagnóstico , Aspergilose Pulmonar Invasiva/tratamento farmacológico , Neuroaspergilose/diagnóstico , Antígenos de Fungos/análise , Aspergillus fumigatus/isolamento & purificação , Aspergillus niger/isolamento & purificação , Cerebelo/microbiologia , Cerebelo/patologia , Criança , Coinfecção/microbiologia , Evolução Fatal , Humanos , Quimioterapia de Indução/efeitos adversos , Lactente , Aspergilose Pulmonar Invasiva/sangue , Aspergilose Pulmonar Invasiva/microbiologia , Masculino , Neuroaspergilose/microbiologia , Neutropenia/induzido quimicamente , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico
8.
Rinsho Ketsueki ; 61(5): 455-461, 2020.
Artigo em Japonês | MEDLINE | ID: mdl-32507808

RESUMO

An 81-year-old female was referred to our hospital with progressive neutropenia and anemia of unknown etiology. We performed a bone marrow biopsy which was notable for hypercellularity, multinucleated megakaryocytes and hypo-granular neutrophils with 2.6% blasts. A diagnosis of myelodysplastic syndrome with multilineage dysplasia (MDS-MLD) was made. Karyotype analysis revealed a t (9;22)(q34;q11.2) BCR-ABL1 fusion with no additional chromosomal abnormalities. BCR-ABL1 was also detected in transcripts from peripheral blood cells as well as in polynuclear leukocytes via FISH. Within one year, her peripheral blood neutrophil count had declined to 403/µl; further analysis was notable for increasing dysplasia including enlarged platelets and hypo-granular neutrophils. Platelet counts gradually increased over time and reached 100×104/µl. A second bone marrow examination revealed similar cell morphology and the BCR-ABL1 translocation. Her condition deteriorated and blood transfusions were required. Treatment with low doses of the tyrosine kinase inhibitor (TKI), imatinib mesylate (100 mg), was initiated. Thereafter, both the neutropenia and anemia resolved gradually, platelet counts returned to normal levels, and dysplasia eventually disappeared. Detection of the BCR-ABL fusion in mRNA decreased to < 0.0007% (IS%) after 16 months of treatment. Several cases of BCR-ABL1-positive myelodysplastic syndrome treated with TKIs have been reported. Our results suggest that complete hematologic recovery in response to imatinib mesylate suggests a critical role for the BCR-ABL1 fusion in the pathogenesis of this disease.


Assuntos
Anemia , Síndromes Mielodisplásicas , Neutropenia , Idoso de 80 Anos ou mais , Anemia/complicações , Feminino , Proteínas de Fusão bcr-abl , Humanos , Mesilato de Imatinib , Síndromes Mielodisplásicas/complicações , Síndromes Mielodisplásicas/tratamento farmacológico , Neutropenia/complicações , Inibidores de Proteínas Quinases
9.
N Engl J Med ; 382(23): 2207-2219, 2020 06 04.
Artigo em Inglês | MEDLINE | ID: mdl-32492302

RESUMO

BACKGROUND: Rituximab added to chemotherapy prolongs survival among adults with B-cell cancer. Data on its efficacy and safety in children with high-grade, mature B-cell non-Hodgkin's lymphoma are limited. METHODS: We conducted an open-label, international, randomized, phase 3 trial involving patients younger than 18 years of age with high-risk, mature B-cell non-Hodgkin's lymphoma (stage III with an elevated lactate dehydrogenase level or stage IV) or acute leukemia to compare the addition of six doses of rituximab to standard lymphomes malins B (LMB) chemotherapy with standard LMB chemotherapy alone. The primary end point was event-free survival. Overall survival and toxic effects were also assessed. RESULTS: Analyses were based on 328 patients who underwent randomization (164 patients per group); 85.7% of the patients had Burkitt's lymphoma. The median follow-up was 39.9 months. Events were observed in 10 patients in the rituximab-chemotherapy group and in 28 in the chemotherapy group. Event-free survival at 3 years was 93.9% (95% confidence interval [CI], 89.1 to 96.7) in the rituximab-chemotherapy group and 82.3% (95% CI, 75.7 to 87.5) in the chemotherapy group (hazard ratio for primary refractory disease or first occurrence of progression, relapse after response, death from any cause, or second cancer, 0.32; 95% CI, 0.15 to 0.66; one-sided P = 0.00096, which reached the significance level required for this analysis). Eight patients in the rituximab-chemotherapy group died (4 deaths were disease-related, 3 were treatment-related, and 1 was from a second cancer), as did 20 in the chemotherapy group (17 deaths were disease-related, and 3 were treatment-related) (hazard ratio, 0.36; 95% CI, 0.16 to 0.82). The incidence of acute adverse events of grade 4 or higher after prephase treatment was 33.3% in the rituximab-chemotherapy group and 24.2% in the chemotherapy group (P = 0.07); events were related mainly to febrile neutropenia and infection. Approximately twice as many patients in the rituximab-chemotherapy group as in the chemotherapy group had a low IgG level 1 year after trial inclusion. CONCLUSIONS: Rituximab added to standard LMB chemotherapy markedly prolonged event-free survival and overall survival among children and adolescents with high-grade, high-risk, mature B-cell non-Hodgkin's lymphoma and was associated with a higher incidence of hypogammaglobulinemia and, potentially, more episodes of infection. (Funded by the Clinical Research Hospital Program of the French Ministry of Health and others; ClinicalTrials.gov number, NCT01516580.).


Assuntos
Antineoplásicos Imunológicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfoma de Células B/tratamento farmacológico , Rituximab/administração & dosagem , Adolescente , Antineoplásicos Imunológicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Infecções/etiologia , Infusões Intravenosas , Estimativa de Kaplan-Meier , Linfoma de Células B/mortalidade , Masculino , Neutropenia/induzido quimicamente , Intervalo Livre de Progressão , Rituximab/efeitos adversos
10.
Nature ; 582(7810): 109-114, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32494068

RESUMO

Advances in genetics and sequencing have identified a plethora of disease-associated and disease-causing genetic alterations. To determine causality between genetics and disease, accurate models for molecular dissection are required; however, the rapid expansion of transcriptional populations identified through single-cell analyses presents a major challenge for accurate comparisons between mutant and wild-type cells. Here we generate mouse models of human severe congenital neutropenia (SCN) using patient-derived mutations in the GFI1 transcription factor. To determine the effects of SCN mutations, we generated single-cell references for granulopoietic genomic states with linked epitopes1, aligned mutant cells to their wild-type equivalents and identified differentially expressed genes and epigenetic loci. We find that GFI1-target genes are altered sequentially, as cells go through successive states of differentiation. These insights facilitated the genetic rescue of granulocytic specification but not post-commitment defects in innate immune effector function, and underscore the importance of evaluating the effects of mutations and therapy within each relevant cell state.


Assuntos
Modelos Animais de Doenças , Células Precursoras de Granulócitos/patologia , Mutação , Neutropenia/genética , Neutropenia/patologia , Neutrófilos/patologia , Animais , Candida albicans/imunologia , Candida albicans/patogenicidade , Linhagem da Célula , Proteínas de Ligação a DNA/genética , Feminino , Humanos , Imunidade Inata , Masculino , Camundongos , Camundongos Transgênicos , Neutropenia/congênito , Neutropenia/imunologia , Neutrófilos/imunologia , Fatores de Transcrição/genética
11.
Tumori ; 106(4): 273-280, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32538316

RESUMO

Neutropenia is the most frequent side effect of commercially available myelosuppressive drugs and its most significant complication is febrile neutropenia. It is associated with increased hospital admissions and higher probability of death. Prophylaxis with the administration of granulocyte colony-stimulating factor can prevent neutropenia caused by anticancer drugs. The correct administration of these drugs and the management of febrile neutropenia are extremely important in the treatment of patients with cancer.


Assuntos
Antineoplásicos/efeitos adversos , Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Neoplasias/tratamento farmacológico , Neutropenia/tratamento farmacológico , Antineoplásicos/uso terapêutico , Gerenciamento Clínico , Guias como Assunto , Humanos , Quimioterapia de Indução/efeitos adversos , Neoplasias/complicações , Neoplasias/patologia , Neutropenia/induzido quimicamente , Neutropenia/patologia
12.
Lung Cancer ; 145: 213-215, 2020 07.
Artigo em Inglês | MEDLINE | ID: covidwho-165217
13.
Lancet Haematol ; 7(6): e490-e497, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32470440

RESUMO

Evaluation of tolerability is increasingly relevant for patients with haematological malignancies treated with chronically administered therapies. Adverse events from these agents might affect the ability of patients to tolerate treatment over time. Conventional toxicity tables that include the incidence of high-grade adverse events, defined by the Common Terminology Criteria for Adverse Events, do not provide information on the time profile of these adverse events or reflect the continuous, lower grade symptomatic toxicities that are particularly relevant to treatment tolerability for patients living with indolent disease. Modern approaches to the evaluation and reporting of toxicity that capture the tolerability of treatment to the patient are imperative. In this Viewpoint, we present a focused, pilot, and longitudinal Toxicity over Time analysis of adverse events from lenalidomide and lenalidomide with rituximab in patients with follicular lymphoma treated in the CALGB 50401 (Alliance; NCT00238238) trial to define the trajectory of adverse events and quantify the burden of continuous, low-grade events. Toxicity over Time analyses provided clinically relevant descriptions of neutropenia and fatigue trajectories caused by lenalidomide that were not identified by standard analysis of the maximum grade events defined by the Common Terminology Criteria for Adverse Events. Systematic, rigorous incorporation of patient-reported outcomes in clinical trials will be crucial to our understanding of the tolerability of chronically administered therapies in patients with haematological malignancies.


Assuntos
Inibidores da Angiogênese/toxicidade , Protocolos de Quimioterapia Combinada Antineoplásica/toxicidade , Neoplasias Hematológicas/tratamento farmacológico , Lenalidomida/toxicidade , Linfoma Folicular/tratamento farmacológico , Inibidores da Angiogênese/efeitos adversos , Antineoplásicos Imunológicos/administração & dosagem , Antineoplásicos Imunológicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Tolerância a Medicamentos/fisiologia , Fadiga/induzido quimicamente , Fadiga/classificação , Fadiga/epidemiologia , Humanos , Infusões Intravenosas , Lenalidomida/efeitos adversos , Neutropenia/induzido quimicamente , Neutropenia/classificação , Neutropenia/epidemiologia , Rituximab/administração & dosagem , Rituximab/uso terapêutico , Trombose/induzido quimicamente , Trombose/classificação , Trombose/epidemiologia
14.
Medicine (Baltimore) ; 99(20): e20022, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32443305

RESUMO

PURPOSE: Febrile neutropenia has a significant clinical and economic impact on cancer patients. This study evaluates the cost-effectiveness of different current empiric antibiotic treatments. METHODS: A decision analytic model was constructed to compare the use of cefepime, meropenem, imipenem/cilastatin, and piperacillin/tazobactam for treatment of high-risk patients. The analysis was performed from the perspective of U.S.-based hospitals. The time horizon was defined to be a single febrile neutropenia episode. Cost-effectiveness was determined by calculating costs and deaths averted. Cost-effectiveness acceptability curves for various willingness-to-pay thresholds (WTP), were used to address the uncertainty in cost-effectiveness. RESULTS: The base-case analysis results showed that treatments were equally effective but differed mainly in their cost. In increasing order: treatment with imipenem/cilastatin cost $52,647, cefepime $57,270, piperacillin/tazobactam $57,277, and meropenem $63,778. In the probabilistic analysis, mean costs were $52,554 (CI: $52,242-$52,866) for imipenem/cilastatin, $57,272 (CI: $56,951-$57,593) for cefepime, $57,294 (CI: $56,978-$57,611) for piperacillin/tazobactam, and $63,690 (CI: $63,370-$64,009) for meropenem. Furthermore, with a WTP set at $0 to $50,000, imipenem/cilastatin was cost-effective in 66.2% to 66.3% of simulations compared to all other high-risk options. DISCUSSION: Imipenem/cilastatin is a cost-effective strategy and results in considerable health care cost-savings at various WTP thresholds. Cost-effectiveness analyses can be used to differentiate the treatments of febrile neutropenia in high-risk patients.


Assuntos
Antibacterianos/economia , Antibacterianos/uso terapêutico , Febre/tratamento farmacológico , Febre/economia , Neutropenia/tratamento farmacológico , Neutropenia/economia , Cefepima/economia , Cefepima/uso terapêutico , Combinação Imipenem e Cilastatina/economia , Combinação Imipenem e Cilastatina/uso terapêutico , Simulação por Computador , Análise Custo-Benefício , Técnicas de Apoio para a Decisão , Febre/mortalidade , Custos de Cuidados de Saúde , Humanos , Meropeném/economia , Meropeném/uso terapêutico , Neutropenia/mortalidade , Combinação Piperacilina e Tazobactam/economia , Combinação Piperacilina e Tazobactam/uso terapêutico , Resultado do Tratamento
15.
Lung Cancer ; 145: 213-215, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32389426
16.
Br J Radiol ; 93(1113): 20190693, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32462888

RESUMO

OBJECTIVE: The aim of this study is to characterize chest CT findings of neutropenic patients with proven/probable invasive pulmonary aspergillosis (IPA). METHODS: Hematological cancer patients admitted to our institution (2007-2017) were retrospectively enrolled if the diagnostic criteria of proven/probable IPA during the neutropenia were met (EORTC/MSG). Galactomannan (GM) was routinely measured in serum and chest CT-scan was routinely performed in case of recurrent/persistent fever. Bronchoscopy was performed in case of chest CT-scan abnormalities. Chest CT-scan and GM dosage were analyzed at the time of IPA suspicion. Chest lesions were classified using a clinical report form by two expert radiologists. RESULTS: 35 patients were identified. Peribronchial focal lesions were observed in 29 IPA (82.9%) by the first radiologist and in 31 (88.5%) by the second (k = 0.768). 12 weeks mortality was 20%. CONCLUSION: Peribronchial focal lesions are a common finding in early-IPA whatever the GM value during neutropenia and our findings reinforce the efficiency of a preemptive approach. ADVANCES IN KNOWLEDGE;: Peribronchial focal lesions, which are classically described in airway invasive aspergillosis, are a common finding in early-IPA in hematological cancer patients with prolonged neutropenia regardless of the GM value, and such peribronchial lesions should reinforce the possibility of IPA.


Assuntos
Broncopatias/diagnóstico por imagem , Neoplasias Hematológicas/complicações , Aspergilose Pulmonar Invasiva/diagnóstico por imagem , Neutropenia/complicações , Tomografia Computadorizada por Raios X , Adulto , Idoso , Biomarcadores/sangue , Broncoscopia , Feminino , Neoplasias Hematológicas/sangue , Humanos , Aspergilose Pulmonar Invasiva/sangue , Masculino , Mananas/sangue , Pessoa de Meia-Idade , Neutropenia/sangue , Neutropenia/induzido quimicamente , Prevalência , Estudos Retrospectivos , Adulto Jovem
17.
Pediatr Blood Cancer ; 67(8): e28234, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32386095

RESUMO

BACKGROUND: Single-center reports of central line-associated bloodstream infection (CLABSI) and the subcategory of mucosal barrier injury laboratory-confirmed bloodstream infection (MBI-LCBI) in pediatric hematology oncology transplant (PHO) patients have focused on the inpatient setting. Characterization of MBI-LCBI across PHO centers and management settings (inpatient and ambulatory) is urgently needed to inform surveillance and prevention strategies. METHODS: Prospectively collected data from August 1, 2013, to December 31, 2015, on CLABSI (including MBI-LCBI) from a US PHO multicenter quality improvement network database was analyzed. CDC National Healthcare Safety Network definitions were applied for inpatient events and adapted for ambulatory events. RESULTS: Thirty-five PHO centers reported 401 ambulatory and 416 inpatient MBI-LCBI events. Ambulatory and inpatient MBI-LCBI rates were 0.085 and 1.01 per 1000 line days, respectively. Fifty-three percent of inpatient CLABSIs were MBI-LCBIs versus 32% in the ambulatory setting (P  <  0.01). Neutropenia was the most common criterion defining MBI-LCBI in both settings, being present in ≥90% of events. The most common organisms isolated in MBI-LCBI events were Escherichia coli (in 28% of events), Klebsiella spp. (23%), and viridans streptococci (12%) in the ambulatory setting and viridans streptococci (in 29% of events), E. coli (14%), and Klebsiella spp. (14%) in the inpatient setting. CONCLUSION: In this largest study of PHO MBI-LCBI inpatient events and the first such study in the ambulatory setting, the burden of MBI-LCBI across the continuum of care of PHO patients was substantial. These data should raise awareness of MBI-LCBI among healthcare providers for PHO patients, help benchmarking across centers, and help inform prevention and treatment strategies.


Assuntos
Infecções Bacterianas , Bases de Dados Factuais , Neoplasias , Neutropenia , Infecções Bacterianas/epidemiologia , Infecções Bacterianas/terapia , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Membrana Mucosa/lesões , Neoplasias/epidemiologia , Neoplasias/terapia , Neutropenia/epidemiologia , Neutropenia/terapia
19.
Cochrane Database Syst Rev ; 5: CD013238, 2020 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-32395825

RESUMO

BACKGROUND: Glioblastoma is an uncommon but highly aggressive type of brain tumour. Significant gains have been achieved in the molecular understanding and the pathogenesis of glioblastomas, however clinical improvements are difficult to obtain for many reasons. The current standard of care involves maximal safe surgical resection followed by chemoradiation and then adjuvant chemotherapy European Organisation for Research and Treatment of Cancer and the NCIC Clinical Trials Group (EORTC-NCIC) protocol with a median survival of 14.6 months. Successive phase III international randomised controlled studies have failed to significantly demonstrate survival advantage with newer drugs. Epidermal growth factor receptor (EGFR) is observed to be aberrant in 30% to 60% of glioblastomas. The receptor aberrancy is driven by abnormal gene amplification, receptor mutation, or both, in particular the extracellular vIII domain. EGFR abnormalities are common in solid tumours, and the advent of anti-EGFR therapies in non-small cell lung cancer and colorectal adenocarcinomas have greatly improved clinical outcomes. Anti-EGFR therapies have been investigated amongst glioblastomas, however questions remain about its ongoing role in glioblastoma management. This review aimed to report on the available evidence to date and perform a systematic analysis on the risks and benefits of use of anti-EGFR therapies in glioblastomas. OBJECTIVES: To evaluate the efficacy and harms of anti-EGFR therapies for glioblastoma in adults. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, EBM Reviews databases, with supplementary handsearches to identify all available and relevant studies to 20 April 2020. SELECTION CRITERIA: All randomised controlled trials (RCTs) using anti-EGFR therapies in adults with glioblastoma were eligible for inclusion. Anti-EGFR therapies included tyrosine kinase inhibitors, monoclonal antibodies, or vaccines. The comparison included investigational product added to standard of care versus standard of care or placebo, or investigational product against standard of care or placebo. DATA COLLECTION AND ANALYSIS: The authorship team screened the search results and recorded the extracted data for analysis. We used standard Cochrane methodology to performed quantitative meta-analysis if two or more studies had appropriate and available data. Otherwise, we conducted a qualitative and descriptive analysis. We used the GRADE system to rate the certainty of the evidence. The analysis was performed along the two clinical settings: first-line (after surgery) and recurrent disease (after failure of first line treatment). Where information was available, we documented overall survival, progression-free survival, adverse events, and quality of life data from eligible studies. MAIN RESULTS: The combined searches initially identified 912 records (after removal of duplicates), and further screening resulted in 19 records for full consideration. We identified nine eligible studies for inclusion in the review. There were three first-line studies and six recurrent studies. Five studies used tyrosine kinase inhibitors (TKIs); two studies used monoclonal antibodies; and two studies used targeted vaccines. More recent studies presented greater detail in the conduct of their studies and thus had a lower risk of bias. We observed no evidence benefit in overall survival with the use of anti-EGFR therapy in the first-line or recurrent setting (hazard ratio (HR) 0.89, 95% confidence interval (CI) 0.76 to 1.04; 3 RCTs, 1000 participants, moderate-certainty evidence; and HR 0.79, 95% CI 0.51 to 1.21, 4 RCTs, 489 participants, low-certainty evidence, respectively). All the interventions were generally well tolerated with low-certainty evidence for lymphopenia (odds ratio (OR) 0.97, 95% CI 0.19 to 4.81; 4 RCTs, 1146 participants), neutropenia (OR 1.29, 95% CI 0.82 to 2.03; 4 RCTs, 1146 participants), and thrombocytopenia (OR 3.69, 95% CI 0.51 to 26.51; 4 RCTs, 1146 participants). A notable toxicity relates to ABT-414, where significant ocular issues were detected. The addition of anti-EGFR therapy showed no evidence of an increase in progression-free survival (PFS) in the first-line setting (HR 0.94, 95% CI 0.81 to 1.10; 2 RCTs, 894 participants, low-certainty evidence). In the recurrent setting, there was an increase in PFS with the use of anti-EGFR therapy (HR 0.75, 95% CI 0.58 to 0.96, 3 RCTs, 275 participants, low-certainty evidence). The available quality of life assessment data showed that anti-EGFR therapies were neither detrimental or beneficial when compared to standard care (not estimable). AUTHORS' CONCLUSIONS: In summary, there is no evidence of a demonstrable overall survival benefit with the addition of anti-EGFR therapy in first-line and recurrent glioblastomas. Newer drugs that are specially designed for glioblastoma targets may raise the possibility of success in this population, but data are lacking at present. Future studies should be more selective in pursuing people displaying specific EGFR targets.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias Encefálicas/tratamento farmacológico , Receptores ErbB/antagonistas & inibidores , Glioblastoma/tratamento farmacológico , Inibidores de Proteínas Quinases/uso terapêutico , Anticorpos Monoclonais/uso terapêutico , Antineoplásicos Imunológicos/uso terapêutico , Neoplasias Encefálicas/mortalidade , Vacinas Anticâncer/uso terapêutico , Progressão da Doença , Glioblastoma/mortalidade , Humanos , Linfopenia/etiologia , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/tratamento farmacológico , Neutropenia/etiologia , Proteínas Tirosina Quinases/antagonistas & inibidores , Ensaios Clínicos Controlados Aleatórios como Assunto , Trombocitopenia/etiologia
20.
Zhongguo Dang Dai Er Ke Za Zhi ; 22(5): 505-511, 2020 May.
Artigo em Chinês | MEDLINE | ID: mdl-32434649

RESUMO

In order to clearly define the features of Shwachman-Diamond syndrome (SDS) in Chinese children, this article analyzes and summarizes the epidemiology, clinical features, and key points in the diagnosis and treatment of SDS in Chinese children with review of the clinical data of 27 children with SDS from related articles published previously. A comparative analysis was made between the Chinese and international data related to childhood SDS. The results showed a male/female ratio of about 2:1 in the Chinese children with SDS, with an age of onset of <1 month to 5 years (median 1 month) and an age of 3 months to 12 years (median 12 months) at the time of confirmed diagnosis. Reductions in peripheral blood cells due to myelopoiesis inhibition were observed in all 27 children with SDS, among whom 93% had neutropenia. Chronic diarrhea (85%), liver damage (78%), and short stature (83%) were the three main clinical features of SDS. Supplementation of pancreatin and component blood transfusion may temporarily alleviate the disease, while allogeneic hematopoietic stem cell transplantation is still an effective radical treatment. The comparative analysis of the Chinese and oversea data showed that compared with those in the European and American countries, the children with SDS in China had significantly higher incidence rates of chronic diarrhea, reductions in peripheral blood cells (three lineages), and liver damage, and there were also differences in the type of mutant genes.


Assuntos
Síndrome de Shwachman-Diamond , Criança , China , Insuficiência Pancreática Exócrina , Feminino , Humanos , Masculino , Neutropenia , Resultado do Tratamento
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