Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 27
Filtrar
1.
4.
Cancer Discov ; 12(4): 958-983, 2022 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-35179201

RESUMO

Vaccination against coronavirus disease 2019 (COVID-19) relies on the in-depth understanding of protective immune responses to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). We characterized the polarity and specificity of memory T cells directed against SARS-CoV-2 viral lysates and peptides to determine correlates with spontaneous, virus-elicited, or vaccine-induced protection against COVID-19 in disease-free and cancer-bearing individuals. A disbalance between type 1 and 2 cytokine release was associated with high susceptibility to COVID-19. Individuals susceptible to infection exhibited a specific deficit in the T helper 1/T cytotoxic 1 (Th1/Tc1) peptide repertoire affecting the receptor binding domain of the spike protein (S1-RBD), a hotspot of viral mutations. Current vaccines triggered Th1/Tc1 responses in only a fraction of all subject categories, more effectively against the original sequence of S1-RBD than that from viral variants. We speculate that the next generation of vaccines should elicit Th1/Tc1 T-cell responses against the S1-RBD domain of emerging viral variants. SIGNIFICANCE: This study prospectively analyzed virus-specific T-cell correlates of protection against COVID-19 in healthy and cancer-bearing individuals. A disbalance between Th1/Th2 recall responses conferred susceptibility to COVID-19 in both populations, coinciding with selective defects in Th1 recognition of the receptor binding domain of spike. See related commentary by McGary and Vardhana, p. 892. This article is highlighted in the In This Issue feature, p. 873.


Assuntos
Fatores de Restrição Antivirais , COVID-19 , Neoplasias , Linfócitos T , Anticorpos Neutralizantes , Fatores de Restrição Antivirais/imunologia , COVID-19/imunologia , Humanos , Neoplasias/complicações , SARS-CoV-2 , Glicoproteína da Espícula de Coronavírus/química , Glicoproteína da Espícula de Coronavírus/genética , Linfócitos T/imunologia
6.
Transpl Infect Dis ; 23(4): e13594, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33650134

RESUMO

Disseminated nocardiosis is a rare but growing concern in immunocompromised patients. Typical localizations include the lung, brain and/or soft tissues, but laboratory confirmation of nocardiosis usually requires sampling of infected organs by invasive procedures such as bronchoalveolar lavage or brain biopsy. We report a case of disseminated nocardiosis occurring in a hematopoietic stem-cell transplant recipient, with clinical lung and brain localizations. Examination of the thyroid gland was suggestive of a unilateral abscess. A culture of thyroid pus sampled by fine-needle aspiration was positive for Nocardia farcinica and therefore avoided a more invasive procedure. The patient recovered after a six-month antibiotic therapy without thyroid surgery. We reviewed other ten cases of thyroid nocardiosis published in the medical literature. Among the ten cases of disseminated nocardiosis established during the patient's lifetime including ours, six (60%) were asymptomatic and seven (70%) were confirmed by culture of the aspiration of thyroid pus. When disseminated nocardiosis is suspected, systematic examination for a thyroid abscess may help establish a microbiological diagnosis and prevent further invasive procedures.


Assuntos
Nocardiose , Nocardia , Humanos , Hospedeiro Imunocomprometido , Nocardiose/diagnóstico , Nocardiose/tratamento farmacológico , Glândula Tireoide/diagnóstico por imagem , Glândula Tireoide/cirurgia
7.
J Surg Oncol ; 123(4): 815-822, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33524172

RESUMO

BACKGROUND AND OBJECTIVES: During the worldwide pandemic of coronavirus disease 2019 (COVID-19), oncological procedures considered to be urgent could not be delayed, and a specific procedure was required to continue surgical activity. The objective was to assess the efficacy of our preoperative screening algorithm. METHODS: This observational retrospective study was performed between the 25th of March and the 12th of May 2020 in a comprehensive cancer center in France. Patients undergoing elective oncologic surgery were tested by preoperative nasopharyngeal reverse-transcription polymerase chain reaction (RT-PCR) that could be associated with a chest computerized tomography (CT) scan. RESULTS: Of the 510 screening tests (in 477 patients), only 5% (15/477) were positive for COVID-19 in 24 patients (18 RT-PCR+ and 7 CT scan+/RT-PCR-). Four patients were ultimately false positives based on the CT scan. In total, only 4.2% (20/477) of the patients were COVID-19+. The positivity rate decreased with time after the containment measures were implemented (from 7.4% to 0.8%). In the COVID-19+ group, 20% of the patients had postoperative pulmonary complications, whereas this was the case for 5% of the patients in the COVID-19 group. CONCLUSIONS: Maintaining secure surgical activity is achievable and paramount in oncology care, even during the COVID-19 pandemic, with appropriate screening based on preoperative RT-PCR.


Assuntos
Teste de Ácido Nucleico para COVID-19 , COVID-19/diagnóstico , Controle de Infecções/organização & administração , Neoplasias/cirurgia , Complicações Pós-Operatórias/epidemiologia , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Adulto , Idoso , Idoso de 80 Anos ou mais , Algoritmos , Institutos de Câncer , Feminino , França , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Neoplasias/complicações , Neoplasias/patologia , Valor Preditivo dos Testes , Cuidados Pré-Operatórios , Reprodutibilidade dos Testes , Estudos Retrospectivos , Tomografia Computadorizada por Raios X , Adulto Jovem
8.
Oncoimmunology ; 9(1): 1807836, 2020 08 25.
Artigo em Inglês | MEDLINE | ID: mdl-32939324

RESUMO

Over the past 16 years, three coronaviruses (CoVs), severe acute respiratory syndrome CoV (SARS-CoV) in 2002, Middle East respiratory syndrome CoV (MERS-CoV) in 2012 and 2015, and SARS-CoV-2 in 2020, have been causing severe and fatal human epidemics. The unpredictability of coronavirus disease-19 (COVID-19) poses a major burden on health care and economic systems across the world. This is caused by the paucity of in-depth knowledge of the risk factors for severe COVID-19, insufficient diagnostic tools for the detection of SARS-CoV-2, as well as the absence of specific and effective drug treatments. While protective humoral and cellular immune responses are usually mounted against these betacoronaviruses, immune responses to SARS-CoV2 sometimes derail towards inflammatory tissue damage, leading to rapid admissions to intensive care units. The lack of knowledge on mechanisms that tilt the balance between these two opposite outcomes poses major threats to many ongoing clinical trials dealing with immunostimulatory or immunoregulatory therapeutics. This review will discuss innate and cognate immune responses underlying protective or deleterious immune reactions against these pathogenic coronaviruses.


Assuntos
COVID-19/imunologia , Interações entre Hospedeiro e Microrganismos/imunologia , SARS-CoV-2/imunologia , COVID-19/diagnóstico , COVID-19/virologia , Humanos , Imunidade Celular , Imunidade Humoral , Coronavírus da Síndrome Respiratória do Oriente Médio/imunologia , Fatores de Proteção , Fatores de Risco , Coronavírus Relacionado à Síndrome Respiratória Aguda Grave/imunologia , Índice de Gravidade de Doença
9.
Cell ; 182(6): 1401-1418.e18, 2020 09 17.
Artigo em Inglês | MEDLINE | ID: mdl-32810439

RESUMO

Blood myeloid cells are known to be dysregulated in coronavirus disease 2019 (COVID-19), caused by SARS-CoV-2. It is unknown whether the innate myeloid response differs with disease severity and whether markers of innate immunity discriminate high-risk patients. Thus, we performed high-dimensional flow cytometry and single-cell RNA sequencing of COVID-19 patient peripheral blood cells and detected disappearance of non-classical CD14LowCD16High monocytes, accumulation of HLA-DRLow classical monocytes (Human Leukocyte Antigen - DR isotype), and release of massive amounts of calprotectin (S100A8/S100A9) in severe cases. Immature CD10LowCD101-CXCR4+/- neutrophils with an immunosuppressive profile accumulated in the blood and lungs, suggesting emergency myelopoiesis. Finally, we show that calprotectin plasma level and a routine flow cytometry assay detecting decreased frequencies of non-classical monocytes could discriminate patients who develop a severe form of COVID-19, suggesting a predictive value that deserves prospective evaluation.


Assuntos
Infecções por Coronavirus , Coronavirus , Pandemias , Pneumonia Viral , Betacoronavirus , COVID-19 , Citometria de Fluxo , Humanos , Complexo Antígeno L1 Leucocitário , Monócitos , Células Mieloides , Estudos Prospectivos , SARS-CoV-2
10.
Mycoses ; 63(5): 443-451, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32048344

RESUMO

BACKGROUND: Invasive fungal infections (IFIs) contribute significantly to nosocomial illness in intensive care units (ICUs). Current practice guidelines recommend echinocandins, such as micafungin, for the treatment of invasive candidiasis. However, limited information on their use in real-world practice is available. OBJECTIVE: To describe the conditions of the use of micafungin in daily clinical practice and to evaluate its effectiveness and tolerability under real-world conditions. PATIENTS/METHODS: This observational, prospective, multicentre study was performed in 34 ICUs in France. The study population consisted of 275 patients ≥16 years old who received treatment with micafungin during the inclusion period. Dose and duration of treatment were at the discretion of the physician. RESULTS: Proven invasive candidiasis was documented before treatment in 106 patients (38.6%); 263 patients (95.6%) received the recommended dose (100 mg/day); 78 patients (28.8%) were treated for the recommended duration. A successful outcome was observed for 217 patients (79.2%). This proportion was significantly higher (83.3%; P < .0001) in patients treated for ≥14 days. Three patients discontinued treatment due to an adverse event considered related to micafungin. No clear impact of micafungin on hepatic function was observed. CONCLUSION: Micafungin was effective in >75% of patients treated for IFIs in ICUs in France; outcomes may be improved with closer adherence to the recommended treatment duration.


Assuntos
Antifúngicos/uso terapêutico , Infecções Fúngicas Invasivas/tratamento farmacológico , Micafungina/uso terapêutico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Candidíase Invasiva/tratamento farmacológico , Feminino , França , Humanos , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Resultado do Tratamento , Adulto Jovem
11.
Nat Cancer ; 1(10): 965-975, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-35121871

RESUMO

Patients with cancer are presumed to be at increased risk of severe COVID-19 outcomes due to underlying malignancy and treatment-induced immunosuppression. Of the first 178 patients managed for COVID-19 at the Gustave Roussy Cancer Centre, 125 (70.2%) were hospitalized, 47 (26.4%) developed clinical worsening and 31 (17.4%) died. An age of over 70 years, smoking status, metastatic disease, cytotoxic chemotherapy and an Eastern Cooperative Oncology Group score of ≥2 at the last visit were the strongest determinants of increased risk of death. In multivariable analysis, the Eastern Cooperative Oncology Group score remained the only predictor of death. In contrast, immunotherapy, hormone therapy and targeted therapy did not increase clinical worsening or death risk. Biomarker studies found that C-reactive protein and lactate dehydrogenase levels were significantly associated with an increased risk of clinical worsening, while C-reactive protein and D-dimer levels were associated with an increased risk of death. COVID-19 management impacted the oncological treatment strategy, inducing a median 20 d delay in 41% of patients and adaptation of the therapeutic strategy in 30% of patients.


Assuntos
COVID-19/epidemiologia , SARS-CoV-2/patogenicidade , Idoso , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
12.
Nat Cancer ; 1(10): 946-964, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-35121872

RESUMO

Coronavirus disease 2019 (COVID-19) and its causative virus, SARS-CoV-2, pose considerable challenges for the management of oncology patients. COVID-19 presents as a particularly severe respiratory and systemic infection in aging and immunosuppressed individuals, including patients with cancer. Moreover, severe COVID-19 is linked to an inflammatory burst and lymphopenia, which may aggravate cancer prognosis. Here we discuss why those with cancer are at higher risk of severe COVID-19, describe immune responses that confer protective or adverse reactions to this disease and indicate which antineoplastic therapies may either increase COVID-19 vulnerability or have a dual therapeutic effect on cancer and COVID-19.


Assuntos
COVID-19/imunologia , Humanos , SARS-CoV-2
13.
Pediatr Infect Dis J ; 38(7): 716-721, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31192976

RESUMO

BACKGROUND: Invasive fungal infections are responsible for significant morbidity and mortality. Safety and effectiveness of antifungal agents is a particular concern in pediatric populations, where data are often limited. Micafungin is an echinocandin with demonstrated antifungal activity against a wide spectrum of Candida spp.; this subanalysis of data from the MYRIADE study describes the use of micafungin and its therapeutic outcomes in pediatric patients, in normal clinical practice. METHODS: MYRIADE was an observational, multicenter, national, prospective, longitudinal study conducted from January 2010 to December 2012, in patients treated with micafungin using a prophylactic or curative strategy, across 17 sites [oncohematology (n = 8), neonatal intensive care units (ICUs) (n = 5) and pediatric ICUs (n = 4)]. The treatment regimen, the achievement of the therapeutic objective and the tolerance were reported. RESULTS: The study population consisted of 110 pediatric patients (31 neonates, 24 children <2 years old and 55 children ≥2 to <16 years old). The therapeutic objective was achieved in 49/64 (76.6%) oncohematology patients, 28/29 (96.6%) neonatal ICU patients and 12/14 (85.7%) pediatric ICU patients. Twenty-four (21.8%) children developed an adverse event (AE); more AEs were observed in oncohematology patients compared with ICU patients [17 (26.1%) vs. 7 (15.6%)]. Only one serious AE, reported in an oncohematology patient, was considered related to micafungin. CONCLUSIONS: In the first large observational study of micafungin treatment or prophylaxis conducted under real-world conditions in France, micafungin was effective and well tolerated for prophylaxis of invasive fungal infections in pediatric oncohematology patients and for curative purposes in pediatric and neonatal ICU patients.


Assuntos
Antifúngicos/administração & dosagem , Candida/isolamento & purificação , Candidíase Invasiva/tratamento farmacológico , Candidíase Invasiva/prevenção & controle , Quimioprevenção/métodos , Micafungina/administração & dosagem , Adolescente , Antifúngicos/efeitos adversos , Quimioprevenção/efeitos adversos , Criança , Pré-Escolar , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Feminino , França , Humanos , Lactente , Recém-Nascido , Estudos Longitudinais , Masculino , Micafungina/efeitos adversos , Estudos Prospectivos , Resultado do Tratamento
15.
Emerg Infect Dis ; 23(6): 1039-1041, 2017 06.
Artigo em Inglês | MEDLINE | ID: mdl-28518017
16.
Infection ; 45(3): 361-363, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27909895

RESUMO

Scopulariopsis brevicaulis onychomycosis with local cutaneous invasion was diagnosed in an acute leukemia patient and unsuccessfully treated with high-dose micafungin, based on antifungal susceptibility testing. This case should alert clinicians to the possible severe evolution of onychomycosis in neutropenic patients and suggests that surgery should be preferred in such a situation.


Assuntos
Equinocandinas/uso terapêutico , Dermatoses do Pé/tratamento farmacológico , Hospedeiro Imunocomprometido , Lipopeptídeos/uso terapêutico , Neutropenia/complicações , Onicomicose/complicações , Onicomicose/tratamento farmacológico , Scopulariopsis/fisiologia , Idoso , Antifúngicos/uso terapêutico , Dermatomicoses/complicações , Dermatomicoses/diagnóstico , Dermatomicoses/tratamento farmacológico , Dermatomicoses/imunologia , Feminino , Dermatoses do Pé/complicações , Dermatoses do Pé/diagnóstico , Dermatoses do Pé/imunologia , Humanos , Micafungina , Neutropenia/imunologia , Onicomicose/diagnóstico , Onicomicose/imunologia , Resultado do Tratamento
17.
J Med Microbiol ; 64(7): 676-681, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25934549

RESUMO

Delay of active antimicrobial therapy in haematological patients with Gram-negative bacilli bacteraemia during profound neutropenia exposes them to increased morbidity and mortality. The digestive tract is the main source of enterobacteria causing bacteraemia in these patients. We thus evaluated the usefulness of broad-spectrum beta-lactam resistant enterobacteria (BSBL-RE) faecal shedding assessment in forecasting the susceptibility to BSBLs of the strains isolated from blood cultures. From 2002 to 2011, neutropenic haematological patients with bacteraemia caused by enterobacteria who had a stool culture during the previous 7 days were retrospectively included. BSBL-RE intestinal carriers were compared with non-carriers in terms of clinical and microbiological criteria. One hundred and four patients were included and 16 of them (15.4 %) were BSBL-RE carriers. Multivariate analysis showed that BSBL-RE carriage was independently associated with BSBL-RE identified in blood cultures (P < 0.001) and the use of carbapenems as empirical treatment of the bacteraemia (P = 0.008). Sensitivity, specificity, and the positive and negative predictive values of the test were 80 %, 91 %, 50 % and 98 %, respectively. Among the carriers, those with the highest level of BSBL-RE carriage were also those with the highest risk of bacteraemia due to BSBL-RE (P < 0.001). Close monitoring of BSBL-RE intestinal carriage may help to choose the most appropriate initial antimicrobial treatment for neutropenic haematological patients with bacteraemia.


Assuntos
Bacteriemia/microbiologia , Farmacorresistência Bacteriana/genética , Infecções por Enterobacteriaceae/microbiologia , Enterobacteriaceae/efeitos dos fármacos , Fezes/microbiologia , Adolescente , Adulto , Idoso , Antibacterianos/uso terapêutico , Bacteriemia/tratamento farmacológico , Carbapenêmicos/uso terapêutico , Enterobacteriaceae/genética , Enterobacteriaceae/isolamento & purificação , Infecções por Enterobacteriaceae/tratamento farmacológico , Feminino , Neoplasias Hematológicas/imunologia , Neoplasias Hematológicas/microbiologia , Humanos , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Neutropenia/complicações , Estudos Retrospectivos , Adulto Jovem , Resistência beta-Lactâmica/genética , beta-Lactamases/genética
18.
Clin Infect Dis ; 61(3): 324-31, 2015 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-25870323

RESUMO

BACKGROUND: Anti-cancer treatment and the cancer population have evolved since the last European Organisation for Research and Treatment of Cancer (EORTC) fungemia survey, and there are few recent large epidemiological studies. METHODS: This was a prospective cohort study including 145 030 admissions of patients with cancer from 13 EORTC centers. Incidence, clinical characteristics, and outcome of fungemia were analyzed. RESULTS: Fungemia occurred in 333 (0.23%; 95% confidence interval [CI], .21-.26) patients, ranging from 0.15% in patients with solid tumors to 1.55% in hematopoietic stem cell transplantation recipients. In 297 evaluable patients age ranged from 17 to 88 years (median 56 years), 144 (48%) patients were female, 165 (56%) had solid tumors, and 140 (47%) had hematological malignancies. Fungemia including polymicrobial infection was due to: Candida spp. in 267 (90%), C. albicans in 128 (48%), and other Candida spp. in 145 (54%) patients. Favorable overall response was achieved in 113 (46.5%) patients by week 2. After 4 weeks, the survival rate was 64% (95% CI, 59%-70%) and was not significantly different between Candida spp. Multivariable logistic regression identified baseline septic shock (odds ratio [OR] 3.04, 95% CI, 1.22-7.58) and tachypnoea as poor prognostic factors (OR 2.95, 95% CI, 1.66-5.24), while antifungal prophylaxis prior to fungemia (OR 0.20, 95% CI, .06-.62) and remission of underlying cancer (OR, 0.18; 95% CI, .06-.50) were protective. CONCLUSIONS: Fungemia, mostly due to Candida spp., was rare in cancer patients from EORTC centers but was associated with substantial mortality. Antifungal prophylaxis and remission of cancer predicted better survival.


Assuntos
Fungemia/complicações , Fungemia/epidemiologia , Leucemia/complicações , Leucemia/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antifúngicos , Candida , Feminino , Fungemia/microbiologia , Fungemia/mortalidade , Humanos , Hospedeiro Imunocomprometido , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Choque Séptico , Adulto Jovem
20.
Bull Cancer ; 101(10): 925-31, 2014 Oct.
Artigo em Francês | MEDLINE | ID: mdl-25373692

RESUMO

BACKGROUND: Febrile neutropenia (FN) is a severe chemotherapy side effect. Hospitalization is recommended for FN episode of high-risk (HR) of complications. Management of FN at lower risk of complications remains unclear. METHODS: This is a prospective observation study in patients with solid tumors admitted to the emergency department FN. Collected data included demographics, clinical, biological, therapeutic costs, MASCC score and complications. RESULTS: Hundred and thirty-seven consecutive FN were recorded in 128 patients. Twenty-six FN (19%) were managed at home (all of them had a MASCC score ≥ 21); 111 (81%) were treated at hospital of which 37 NF were at HR of complications based on clinical and biological parameters (all of them had a MASCC score < 21) and for 74 of them the admission could be discussed (MASCC < 20 or ≥ 20). This group of patients was considerate with intermediate risk (IR). All IR patients were treated with the same antibiotics than outpatients, i.e. ceftriaxone in 36 cases (49%) or amoxicillin/clavulanic acid and ciprofloxacin in 38 cases (51%). For these 74 cases, any severe complication was recorded. Antibiotics were adapted for only 12% of these patients according to bacteriology results. CONCLUSION: This study showed the limits of the MASCC score. We did not observe any severe complications in patients admitted to the hospital according to clinical and biological parameters and with the high risk score MASCC. This study had some methodological bias but it allowed us to estimate the cost of the different ways of management and the difficulties to decide the hospitalization in FN.


Assuntos
Antibacterianos/uso terapêutico , Serviço Hospitalar de Emergência/estatística & dados numéricos , Neutropenia Febril/tratamento farmacológico , Hospitalização/estatística & dados numéricos , Neoplasias/tratamento farmacológico , Adulto , Idoso , Assistência Ambulatorial/economia , Assistência Ambulatorial/estatística & dados numéricos , Combinação Amoxicilina e Clavulanato de Potássio/uso terapêutico , Antibacterianos/efeitos adversos , Antineoplásicos/efeitos adversos , Institutos de Câncer , Ceftriaxona/uso terapêutico , Ciprofloxacina/uso terapêutico , Serviço Hospitalar de Emergência/economia , Neutropenia Febril/induzido quimicamente , Neutropenia Febril/microbiologia , Feminino , França , Hospitalização/economia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Medição de Risco , Adulto Jovem
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...