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1.
Age Ageing ; 53(1)2024 01 02.
Artigo em Inglês | MEDLINE | ID: mdl-38167925

RESUMO

BACKGROUND: The use of myocardial reperfusion-mainly via angioplasty-has increased in our region to over 95%. We wondered whether old and very old patients have benefited from this development. METHODS: Setting: Greater Paris Area (Ile-de-France). DATA: Regional registry, prospective, including since 2003, data from 39 mobile intensive care units performing prehospital treatment of patients with ST segment elevation myocardial infarction (STEMI) (<24 h). PARAMETERS: Demographic, decision to perform reperfusion and outcome (in-hospital mortality). PRIMARY ENDPOINT: Reperfusion decision rate by decade over age 70. SECONDARY ENDPOINT: Outcome. RESULTS: We analysed the prehospital management of 27,294 patients. There were 21,311 (78%) men and 5,919 (22%) women with a median age of 61 (52-73 years). Among these patients, 8,138 (30%) were > 70 years, 3,784 (14%) > 80 years and 672 (2%) > 90 years.The reperfusion decision rate was 94%. It decreased significantly with age: 93, 90 and 76% in patients in their seventh, eighth and ninth decade, respectively. The reperfusion decision rate increased significantly over time. It increased in all age groups, especially the higher ones. Mortality was 6%. It increased significantly with age: 8, 16 and 25% in patients in their seventh, eighth and ninth decade, respectively. It significantly decreased over time in all age groups. The odds ratio of the impact of reperfusion decision on mortality reached 0.42 (0.26-0.68) in patients over 90 years. CONCLUSION: the increase in the reperfusion decision rate was the greatest in the oldest patients. It reduced mortality even in patients over 90 years of age.


Assuntos
Infarto do Miocárdio com Supradesnível do Segmento ST , Masculino , Humanos , Feminino , Idoso de 80 Anos ou mais , Idoso , Infarto do Miocárdio com Supradesnível do Segmento ST/diagnóstico , Infarto do Miocárdio com Supradesnível do Segmento ST/terapia , Estudos Prospectivos , Reperfusão Miocárdica/efeitos adversos , Mortalidade Hospitalar , França/epidemiologia , Resultado do Tratamento , Sistema de Registros
2.
Crit Care ; 27(1): 496, 2023 12 20.
Artigo em Inglês | MEDLINE | ID: mdl-38124126

RESUMO

BACKGROUND: Epinephrine increases the chances of return of spontaneous circulation (ROSC) in out-of-hospital cardiac arrest (OHCA), especially when the initial rhythm is non-shockable. However, this drug could also worsen the post-resuscitation syndrome (PRS). We assessed the association between epinephrine use during cardiopulmonary resuscitation (CPR) and subsequent intensive care unit (ICU) mortality in patients with ROSC after non-shockable OHCA. METHODS: We used data prospectively collected in the Sudden Death Expertise Center (SDEC) registry (capturing OHCA data located in the Greater Paris area, France) between May 2011 and December 2021. All adults with ROSC after medical, cardiac and non-cardiac causes, non-shockable OHCA admitted to an ICU were included. The mode of death in the ICU was categorized as cardiocirculatory, neurological, or other. RESULTS: Of the 2,792 patients analyzed, there were 242 (8.7%) survivors at hospital discharge, 1,004 (35.9%) deaths from cardiocirculatory causes, 1,233 (44.2%) deaths from neurological causes, and 313 (11.2%) deaths from other etiologies. The cardiocirculatory death group received more epinephrine (4.6 ± 3.8 mg versus 1.7 ± 2.8 mg, 3.2 ± 2.6 mg, and 3.5 ± 3.6 mg for survivors, neurological deaths, and other deaths, respectively; p < 0.001). The proportion of cardiocirculatory death increased linearly (R2 = 0.92, p < 0.001) with cumulative epinephrine doses during CPR (17.7% in subjects who did not receive epinephrine and 62.5% in those who received > 10 mg). In multivariable analysis, a cumulative dose of epinephrine was strongly associated with cardiocirculatory death (adjusted odds ratio of 3.45, 95% CI [2.01-5.92] for 1 mg of epinephrine; 12.28, 95% CI [7.52-20.06] for 2-5 mg; and 23.71, 95% CI [11.02-50.97] for > 5 mg; reference 0 mg; population reference: alive at hospital discharge), even after adjustment on duration of resuscitation. The other modes of death (neurological and other causes) were also associated with epinephrine use, but to a lesser extent. CONCLUSIONS: In non-shockable OHCA with ROSC, the dose of epinephrine used during CPR is strongly associated with early cardiocirculatory death. Further clinical studies aimed at limiting the dose of epinephrine during CPR seem warranted. Moreover, strategies for the prevention and management of PRS should take this dose of epinephrine into consideration for future trials.


Assuntos
Reanimação Cardiopulmonar , Serviços Médicos de Emergência , Parada Cardíaca Extra-Hospitalar , Adulto , Humanos , Reanimação Cardiopulmonar/efeitos adversos , Parada Cardíaca Extra-Hospitalar/epidemiologia , Epinefrina/uso terapêutico , Sistema de Registros
3.
Emerg Med J ; 40(11): 761-767, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37640438

RESUMO

OBJECTIVE: Over 300 000 cases of out-of-hospital cardiac arrests (OHCAs) occur each year in the USA and Europe. Despite decades of investment and research, survival remains disappointingly low. We report the trends in survival after a ventricular fibrillation/pulseless ventricular tachycardia OHCA, over a 13-year period, in a French urban region, and describe the simultaneous evolution of the rescue system. METHODS: We investigated four 18-month periods between 2005 and 2018. The first period was considered baseline and included patients from the randomised controlled trial 'DEFI 2005'. The three following periods were based on the Paris Sudden Death Expertise Center Registry (France). Inclusion criteria were non-traumatic cardiac arrests treated with at least one external electric shock with an automated external defibrillator from the basic life support team and resuscitated by a physician-staffed ALS team. Primary outcome was survival at hospital discharge with a good neurological outcome. RESULTS: Of 21 781 patients under consideration, 3476 (16%) met the inclusion criteria. Over all study periods, survival at hospital discharge increased from 12% in 2005 to 25% in 2018 (p<0.001), and return of spontaneous circulation at hospital admission increased from 43% to 58% (p=0.004).Lay-rescuer cardiopulmonary resuscitation (CPR) and telephone CPR (T-CPR) rates increased significantly, but public defibrillator use remained limited. CONCLUSION: In a two-tiered rescue system, survival from OHCA at hospital discharge doubled over a 13-year study period. Concomitantly, the system implemented an OHCA patient registry and increased T-CPR frequency, despite a consistently low rate of public defibrillator use.


Assuntos
Reanimação Cardiopulmonar , Serviços Médicos de Emergência , Parada Cardíaca Extra-Hospitalar , Humanos , Estudos Retrospectivos , Desfibriladores , Arritmias Cardíacas
5.
Crit Care ; 25(1): 369, 2021 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-34774087

RESUMO

BACKGROUND: Extracorporeal cardiopulmonary resuscitation (E-CPR) is used for the treatment of refractory cardiac arrest. However, the optimal target to reach for mean arterial pressure (MAP) remains to be determined. We hypothesized that MAP levels critically modify cerebral hemodynamics during E-CPR and tested two distinct targets (65-75 vs 80-90 mmHg) in a porcine model. METHODS: Pigs were submitted to 15 min of untreated ventricular fibrillation followed by 30 min of E-CPR. Defibrillations were then delivered until return of spontaneous circulation (ROSC). Extracorporeal circulation was initially set to an average flow of 40 ml/kg/min. The dose of epinephrine was set to reach a standard or a high MAP target level (65-75 vs 80-90 mmHg, respectively). Animals were followed during 120-min after ROSC. RESULTS: Six animals were included in both groups. During E-CPR, high MAP improved carotid blood flow as compared to standard MAP. After ROSC, this was conversely decreased in high versus standard MAP, while intra-cranial pressure was superior. The pressure reactivity index (PRx), which is the correlation coefficient between arterial blood pressure and intracranial pressure, also demonstrated inverted patterns of alteration according to MAP levels during E-CPR and after ROSC. In standard-MAP, PRx was transiently positive during E-CPR before returning to negative values after ROSC, demonstrating a reversible alteration of cerebral autoregulation during E-CPR. In high-MAP, PRx was negative during E-CPR but became sustainably positive after ROSC, demonstrating a prolonged alteration in cerebral autoregulation after ROSC. It was associated with a significant decrease in cerebral oxygen consumption in high- versus standard-MAP after ROSC. CONCLUSIONS: During early E-CPR, MAP target above 80 mmHg is associated with higher carotid blood flow and improved cerebral autoregulation. This pattern is inverted after ROSC with a better hemodynamic status with standard versus high-MAP.


Assuntos
Pressão Arterial , Reanimação Cardiopulmonar , Circulação Cerebrovascular , Oxigenação por Membrana Extracorpórea , Animais , Pressão Arterial/fisiologia , Reanimação Cardiopulmonar/métodos , Circulação Cerebrovascular/fisiologia , Hemodinâmica , Suínos , Resultado do Tratamento
6.
Eur Heart J ; 41(21): 1961-1971, 2020 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-31670793

RESUMO

AIMS: Out-of-hospital cardiac arrest (OHCA) without return of spontaneous circulation (ROSC) despite conventional resuscitation is common and has poor outcomes. Adding extracorporeal membrane oxygenation (ECMO) to cardiopulmonary resuscitation (extracorporeal-CPR) is increasingly used in an attempt to improve outcomes. METHODS AND RESULTS: We analysed a prospective registry of 13 191 OHCAs in the Paris region from May 2011 to January 2018. We compared survival at hospital discharge with and without extracorporeal-CPR and identified factors associated with survival in patients given extracorporeal-CPR. Survival was 8% in 525 patients given extracorporeal-CPR and 9% in 12 666 patients given conventional-CPR (P = 0.91). By adjusted multivariate analysis, extracorporeal-CPR was not associated with hospital survival [odds ratio (OR), 1.3; 95% confidence interval (95% CI), 0.8-2.1; P = 0.24]. By conditional logistic regression with matching on a propensity score (including age, sex, occurrence at home, bystander CPR, initial rhythm, collapse-to-CPR time, duration of resuscitation, and ROSC), similar results were found (OR, 0.8; 95% CI, 0.5-1.3; P = 0.41). In the extracorporeal-CPR group, factors associated with hospital survival were initial shockable rhythm (OR, 3.9; 95% CI, 1.5-10.3; P = 0.005), transient ROSC before ECMO (OR, 2.3; 95% CI, 1.1-4.7; P = 0.03), and prehospital ECMO implantation (OR, 2.9; 95% CI, 1.5-5.9; P = 0.002). CONCLUSIONS: In a population-based registry, 4% of OHCAs were treated with extracorporeal-CPR, which was not associated with increased hospital survival. Early ECMO implantation may improve outcomes. The initial rhythm and ROSC may help select patients for extracorporeal-CPR.


Assuntos
Reanimação Cardiopulmonar , Serviços Médicos de Emergência , Parada Cardíaca Extra-Hospitalar , Humanos , Parada Cardíaca Extra-Hospitalar/terapia , Paris/epidemiologia , Sistema de Registros
7.
Circulation ; 139(10): 1262-1271, 2019 03 05.
Artigo em Inglês | MEDLINE | ID: mdl-30586753

RESUMO

BACKGROUND: In out-of-hospital cardiac arrest (OHCA), geographic disparities in outcomes may reflect baseline variations in patients' characteristics but may also result from differences in the number of ambulances providing basic life support (BLS) and advanced life support (ALS). We aimed at assessing the association between allocated ambulance resources and outcomes in OHCA patients in a large urban community. METHODS: From May 2011 to January 2016, we analyzed a prospectively collected Utstein database for all OHCA adults. Cases were geocoded according to 19 neighborhoods and the number of BLS (firefighters performing cardiopulmonary resuscitation and applying automated external defibrillator) and ALS ambulances (medicalized team providing advanced care such as drugs and endotracheal intubation) was collected. We assessed the respective associations of Utstein parameters, socioeconomic characteristics, and ambulance resources of these neighborhoods using a mixed-effect model with successful return of spontaneous circulation as the primary end point and survival at hospital discharge as a secondary end point. RESULTS: During the study period, 8754 nontraumatic OHCA occurred in the Greater Paris area. Overall return of spontaneous circulation rate was 3675 of 8754 (41.9%) and survival rate at hospital discharge was 788 of 8754 (9%), ranging from 33% to 51.1% and from 4.4% to 14.5% respectively, according to neighborhoods ( P<0.001). Patient and socio-demographic characteristics significantly differed between neighborhoods ( P for trend <0.001). After adjustment, a higher density of ambulances was associated with successful return of spontaneous circulation (respectively adjusted odds-ratio [aOR], 1.31 [1.14-1.51]; P<0.001 for ALS ambulances >1.5 per neighborhood and aOR, 1.21 [1.04-1.41]; P=0.01 for BLS ambulances >4 per neighborhood). Regarding survival at discharge, only the number of ALS ambulances >1.5 per neighborhood was significant (aOR, 1.30 [1.06-1.59] P=0.01). CONCLUSIONS: In this large urban population-based study of out-of-hospital cardiac arrests patients, we observed that allocated resources of emergency medical service are associated with outcome, suggesting that improving healthcare organization may attenuate disparities in prognosis.


Assuntos
Suporte Vital Cardíaco Avançado , Ambulâncias/provisão & distribuição , Reanimação Cardiopulmonar , Alocação de Recursos para a Atenção à Saúde , Disparidades em Assistência à Saúde , Parada Cardíaca Extra-Hospitalar/terapia , Serviços Urbanos de Saúde/provisão & distribuição , Idoso , Idoso de 80 Anos ou mais , Bases de Dados Factuais , Desfibriladores/provisão & distribuição , Cardioversão Elétrica/instrumentação , Auxiliares de Emergência/provisão & distribuição , Feminino , Bombeiros , Mortalidade Hospitalar , Humanos , Masculino , Pessoa de Meia-Idade , Parada Cardíaca Extra-Hospitalar/diagnóstico , Parada Cardíaca Extra-Hospitalar/mortalidade , Parada Cardíaca Extra-Hospitalar/fisiopatologia , Paris , Recuperação de Função Fisiológica , Sistema de Registros , Características de Residência , Estudos Retrospectivos , Fatores de Risco , Determinantes Sociais da Saúde , Fatores Socioeconômicos , Fatores de Tempo , Resultado do Tratamento
9.
Am Heart J ; 222: 131-138, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32059120

RESUMO

BACKGROUND: In adults, the most common cause of out-of-hospital cardiac arrests (OHCA) is acute coronary artery occlusion. If an immediate coronary angiogram (CAG) is recommended for survivors presenting a ST segment elevation on the electrocardiogram (ECG) performed after resuscitation, there is still a debate regarding the best strategy in patients without ST segment elevation. HYPOTHESIS: Performing an immediate CAG after an OHCA without ST segment elevation on the post-resuscitation ECG and no obvious non-cardiac cause of arrest could lead to a better 180-day survival rate with no or minimal neurological sequel as compared with a delayed CAG performed 48 to 96 hours after the arrest. DESIGN: The EMERGE trial is a prospective national, randomized, open and parallel group trial, in which 970 survivors of OHCA will be randomized (1:1) to either immediate (as soon as possible after return of spontaneous circulation) or delayed (48 to 96 h) CAG. Participants will be OHCA patients with no ST segment elevation on the post resuscitation ECG and no obvious non-cardiac cause of arrest. The primary endpoint of the study is the 180-day survival rate with no or minimal neurological sequel corresponding to Cerebral Performance Category (CPC) 1 or 2. The secondary endpoints are: occurrence of shock during the first 48 hours, ventricular tachycardia and/or fibrillation during the first 48 hours, change in left ventricular ejection fraction between baseline and 180 days assessed by echocardiogram, neurological status evaluated by the CPC score at intensive care unit (ICU) discharge and day 90 neurological status assessed by the Glasgow Outcome Scale Extended score (GOSE) at 90 and 180 days, overall survival rate, and hospital length of stay. SUMMARY: The EMERGE trial is a prospective, multicenter, randomized, controlled trial that will assess the 180-day survival rate with no or minimal neurologic sequel in patients resuscitated from an OHCA without ST segment elevation and who will be managed with either immediate or delayed CAG.


Assuntos
Angiografia Coronária/métodos , Oclusão Coronária/diagnóstico , Diagnóstico Tardio , Diagnóstico Precoce , Serviço Hospitalar de Emergência , Parada Cardíaca Extra-Hospitalar/diagnóstico , Sistema de Registros , Adulto , Idoso , Reanimação Cardiopulmonar/métodos , Oclusão Coronária/complicações , Oclusão Coronária/mortalidade , Eletrocardiografia , Feminino , Seguimentos , França/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Parada Cardíaca Extra-Hospitalar/etiologia , Parada Cardíaca Extra-Hospitalar/terapia , Estudos Prospectivos , Taxa de Sobrevida/tendências , Sobreviventes , Fatores de Tempo
10.
Crit Care ; 23(1): 391, 2019 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-31796127

RESUMO

PURPOSE: Recent doubts regarding the efficacy may have resulted in a loss of interest for targeted temperature management (TTM) in comatose cardiac arrest (CA) patients, with uncertain consequences on outcome. We aimed to identify a change in TTM use and to assess the relationship between this change and neurological outcome. METHODS: We used Utstein data prospectively collected in the Sudden Death Expertise Center (SDEC) registry (capturing CA data from all secondary and tertiary hospitals located in the Great Paris area, France) between May 2011 and December 2017. All cases of non-traumatic OHCA patients with stable return of spontaneous circulation (ROSC) were included. After adjustment for potential confounders, we assessed the relationship between changes over time in the use of TTM and neurological recovery at discharge using the Cerebral Performance Categories (CPC) scale. RESULTS: Between May 2011 and December 2017, 3925 patients were retained in the analysis, of whom 1847 (47%) received TTM. The rate of good neurological outcome at discharge (CPC 1 or 2) was higher in TTM patients as compared with no TTM (33% vs 15%, P < 0.001). Gender, age, and location of CA did not change over the years. Bystander CPR increased from 55% in 2011 to 73% in 2017 (P < 0.001) and patients with a no-flow time longer than 3 min decreased from 53 to 38% (P < 0.001). The use of TTM decreased from 55% in 2011 to 37% in 2017 (P < 0.001). Meanwhile, the rate of patients with good neurological recovery remained stable (19 to 23%, P = 0.76). After adjustment, year of CA occurrence was not associated with outcome. CONCLUSIONS: We report a progressive decrease in the use of TTM in post-cardiac arrest patients over the recent years. During this period, neurological outcome remained stable, despite an increase in bystander-initiated resuscitation and a decrease in "no flow" duration.


Assuntos
Hipotermia Induzida/normas , Parada Cardíaca Extra-Hospitalar/terapia , Avaliação de Resultados em Cuidados de Saúde/estatística & dados numéricos , Fatores de Tempo , Resultado do Tratamento , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Hipotermia Induzida/métodos , Hipotermia Induzida/estatística & dados numéricos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Parada Cardíaca Extra-Hospitalar/epidemiologia , Avaliação de Resultados em Cuidados de Saúde/normas , Paris/epidemiologia , Sistema de Registros/estatística & dados numéricos
11.
Eur Heart J ; 39(21): 1981-1987, 2018 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-29566157

RESUMO

Aims: Recent studies have shown that in more than half of apparently unexplained sudden cardiac arrests (SCA), a specific aetiology can be unmasked by a careful evaluation. The characteristics and the extent to which such cases undergo a systematic thorough investigation in real-life practice are unknown. Methods and results: Data were analysed from an ongoing study, collecting all cases of out-of-hospital cardiac arrest in Paris area. Investigations performed during the index hospitalization or planned after discharge were gathered to evaluate the completeness of assessment of unexplained SCA. Between 2011 and 2016, among the 18 622 out-of-hospital cardiac arrests, 717 survivors (at hospital discharge) fulfilled the definition of cardiac SCA. Of those, 88 (12.3%) remained unexplained after electrocardiogram, echocardiography, and coronary angiography. Cardiac magnetic resonance imaging yielded the diagnosis in 25 (3.5%) cases, other investigations accounted for 14 (2.4%) additional diagnoses, and 49 (6.8%) patients were labelled as idiopathic ventricular fibrillation (IVF) (48.7 ± 15 years, 69.4% male). Among those labelled IVF, only 8 (16.3%) cases benefited from a complete workup (including pharmacological testing). Younger patients [odds ratio (OR) 6.00, 95% confidence interval (CI) 1.80-22.26] and those admitted to university centres (OR 3.60, 95% CI 1.12-12.45) were more thoroughly investigated. Genetic testing and family screening were initiated in only 9 (18.4%) and 12 (24.5%) cases, respectively. Conclusion: Our findings suggest that complete investigations are carried out in a very low proportion of unexplained SCA. Standardized, systematic approaches need to be implemented to ensure that opportunities for specific therapies and preventive strategies (including relatives) are not missed.


Assuntos
Morte Súbita Cardíaca/etiologia , Parada Cardíaca Extra-Hospitalar/etiologia , Fibrilação Ventricular/diagnóstico , Adulto , Idoso , Arritmias Cardíacas/complicações , Arritmias Cardíacas/diagnóstico , Doença do Sistema de Condução Cardíaco/complicações , Doença do Sistema de Condução Cardíaco/diagnóstico , Cardiomiopatias/complicações , Cardiomiopatias/diagnóstico , Angiografia Coronária , Doença da Artéria Coronariana/complicações , Doença da Artéria Coronariana/diagnóstico , Ecocardiografia , Eletrocardiografia , Família , Feminino , Testes Genéticos , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Sobreviventes , Fibrilação Ventricular/complicações , Fibrilação Ventricular/genética
12.
Crit Care Med ; 46(6): e523-e529, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29543597

RESUMO

OBJECTIVES: To investigate the magnitude of lactic acidosis in response to cyanide poisoning compared with the secondary response caused by cardiovascular shock. DESIGN: Retrospective case-control observational study. SETTING: University Hospital of Assistance Publique - Hôpitaux de Paris. SUBJECTS: Patients admitted for suspicion of cyanide poisoning or drug overdose. Medical charts provided by Assistance Publique - Hôpitaux de Paris of patients between January 1988 and December 2015. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: Twelve cyanide poisoned patients were matched to 48 controls by age, sex, systolic blood pressure, catecholamine administration, and outcome at discharge from ICU. Extracted data included age, sex, vital signs, symptoms, biochemical parameters, toxicological analysis, treatment, and outcome. Non-parametric tests were used. Multivariable analysis was used to adjust for confounders causing hyperlactacidemia. The median blood lactate concentration was significantly greater in the cyanide group (15.6 mmol/L) compared to the control group (4.1 mmol/L; p = 0.0003). Similarly, blood lactate concentration greater than or equal to 8 mmol/l was observed in 83% of the cyanide cases versus 27% of the matched controls. Multivariate analysis conferred hyperlactacidemia as the lone factor which significantly predicted cyanide poisoning at an odds of 73.0 (5.7-936.1). Moreover, blood cyanide level significantly correlated with the increase of blood lactate (p = 0.0033). CONCLUSIONS: This study supports the hypothesis lactic acidosis primarily results from the direct toxicity of cyanide.


Assuntos
Acidose Láctica/induzido quimicamente , Cianetos/intoxicação , Acidose Láctica/etiologia , Adolescente , Adulto , Idoso , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Choque Cardiogênico/complicações , Adulto Jovem
13.
Haematologica ; 103(5): 778-786, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29472357

RESUMO

Sickle cell disease is characterized by chronic anemia and vaso-occlusive crises, which eventually lead to multi-organ damage and premature death. Hematopoietic stem cell transplantation is the only curative treatment but it is limited by toxicity and poor availability of HLA-compatible donors. A gene therapy approach based on the autologous transplantation of lentiviral-corrected hematopoietic stem and progenitor cells was shown to be efficacious in one patient. However, alterations of the bone marrow environment and properties of the red blood cells hamper the harvesting and immunoselection of patients' stem cells from bone marrow. The use of Filgrastim to mobilize large numbers of hematopoietic stem and progenitor cells into the circulation has been associated with severe adverse events in sickle cell patients. Thus, broader application of the gene therapy approach requires the development of alternative mobilization methods. We set up a phase I/II clinical trial whose primary objective was to assess the safety of a single injection of Plerixafor in sickle cell patients undergoing red blood cell exchange to decrease the hemoglobin S level to below 30%. The secondary objective was to measure the efficiency of mobilization and isolation of hematopoietic stem and progenitor cells. No adverse events were observed. Large numbers of CD34+ cells were mobilized extremely quickly. Importantly, the mobilized cells contained high numbers of hematopoietic stem cells, expressed high levels of stemness genes, and engrafted very efficiently in immunodeficient mice. Thus, Plerixafor can be safely used to mobilize hematopoietic stem cells in sickle cell patients; this finding opens up new avenues for treatment approaches based on gene addition and genome editing. Clinicaltrials.gov identifier: NCT02212535.


Assuntos
Anemia Falciforme/terapia , Transfusão de Sangue , Mobilização de Células-Tronco Hematopoéticas , Transplante de Células-Tronco Hematopoéticas , Células-Tronco Hematopoéticas/efeitos dos fármacos , Células-Tronco Hematopoéticas/metabolismo , Compostos Heterocíclicos/administração & dosagem , Anemia Falciforme/metabolismo , Anemia Falciforme/patologia , Fármacos Anti-HIV/administração & dosagem , Antígenos CD34/metabolismo , Antidrepanocíticos/administração & dosagem , Benzilaminas , Estudos de Casos e Controles , Células Cultivadas , Estudos de Coortes , Ciclamos , Células-Tronco Hematopoéticas/citologia , Humanos , Hidroxiureia/administração & dosagem
14.
Transpl Infect Dis ; 20(2): e12846, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29360195

RESUMO

BACKGROUND: Donor (D)+/recipient (R)- serostatus is closely associated with a higher risk of cytomegalovirus (CMV) infection and disease. Antiviral prophylaxis is conventionally used in such patients, but late onset CMV infection/disease still occurs after the discontinuation of prophylaxis. METHODS: We retrospectively analyzed the data of 215 low immunological risk patients who received kidney transplantation in our center between 2011 and 2016. RESULTS: Ninety-seven patients received a combination of everolimus (EVL)/reduced doses of calcineurin inhibitors (CNI) (EVL group) de novo, and 118 received a combination of mycophenolic acid (MPA)/standard doses of CNI (MPA group) de novo. All patients received induction by basiliximab, steroids, and standardized antiviral prophylaxis depending on their CMV D/R serostatus. D+/R- recipients comprised 17% (n = 16) of the EVL group and 19% (n = 22) of the MPA group (P = .722). In the D+/R- subgroup, the 1-year incidence of late onset CMV primary disease after the withdrawal of prophylaxis was lower in the EVL group than in the MPA group (6% vs 41%, P = .025) while the rate of CMV disease in the D+/R+ group (8% vs 6%, P = 1) and the D-/R+ group (12% vs 9%, P = 1) were similar. Kaplan-Meier analysis of 1-year CMV primary disease-free survival in seronegative patients was significantly better in the EVL group (P = .029, log-rank test). CONCLUSIONS: Our data suggest that de novo use of EVL may reduce late onset CMV primary disease after the withdrawal of antiviral prophylaxis in kidney transplantation patients.


Assuntos
Antivirais/administração & dosagem , Infecções por Citomegalovirus/prevenção & controle , Everolimo/farmacologia , Transplante de Rim , Adulto , Idoso , Antivirais/uso terapêutico , Estudos de Coortes , Everolimo/administração & dosagem , Feminino , Rejeição de Enxerto/prevenção & controle , Humanos , Imunossupressores/uso terapêutico , Masculino , Pessoa de Meia-Idade , Transplantados
16.
Circulation ; 134(25): 2074-2083, 2016 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-27793995

RESUMO

BACKGROUND: In-hospital mortality of ST-segment-elevation myocardial infarction (STEMI) has decreased drastically. In contrast, prehospital mortality from sudden cardiac arrest (SCA) remains high and difficult to reduce. Identification of the patients with STEMI at higher risk for prehospital SCA could facilitate rapid triage and intervention in the field. METHODS: Using a prospective, population-based study evaluating all patients with STEMI managed by emergency medical services in the greater Paris area (11.7 million inhabitants) between 2006 and 2010, we identified characteristics associated with an increased risk of prehospital SCA and used these variables to build an SCA prediction score, which we validated internally and externally. RESULTS: In the overall STEMI population (n=8112; median age, 60 years; 78% male), SCA occurred in 452 patients (5.6%). In multivariate analysis, younger age, absence of obesity, absence of diabetes mellitus, shortness of breath, and a short delay between pain onset and call to emergency medical services were the main predictors of SCA. A score built from these variables predicted SCA, with the risk increasing 2-fold in patients with a score between 10 and 19, 4-fold in those with a score between 20 and 29, and >18-fold in patients with a score ≥30 compared with those with scores <10. The SCA rate was 28.9% in patients with a score ≥30 compared with 1.6% in patients with a score ≤9 (P for trend <0.001). The area under the curve values were 0.7033 in the internal validation sample and 0.6031 in the external validation sample. Sensitivity and specificity varied between 96.9% and 10.5% for scores ≥10 and between 18.0% and 97.6% for scores ≥30, with scores between 20 and 29 achieving the best sensitivity and specificity (65.4% and 62.6%, respectively). CONCLUSIONS: At the early phase of STEMI, the risk of prehospital SCA can be determined through a simple score of 5 routinely assessed predictors. This score might help optimize the dispatching and management of patients with STEMI by emergency medical services.


Assuntos
Morte Súbita Cardíaca/etiologia , Infarto do Miocárdio/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Área Sob a Curva , Dor no Peito/etiologia , Morte Súbita Cardíaca/epidemiologia , Eletrocardiografia , Serviços Médicos de Emergência , Feminino , Mortalidade Hospitalar , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Infarto do Miocárdio/complicações , Estudos Prospectivos , Curva ROC , Fatores de Risco , Inquéritos e Questionários , Telefone
18.
Transpl Int ; 30(8): 799-806, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28152216

RESUMO

Two end-stage renal disease (ESRD) risk calculators were recently developed by Grams et al., and Ibrahim et al. to calculate ESRD risk before donation among living kidney donors. However, those calculators have never been studied among potential donors for whom donation was refused due to medical contraindications and compared to a group of donors. We compared 15-year and lifetime ESRD risk of donors and nondonors due to medical cause as estimated by those two calculators. Nondonors due to medical cause (n = 27) had a significantly higher 15-year ESRD risk compared to donors (n = 288) with both calculators (0.25 vs. 0.14, P < 0.001 for that developed by Grams et al. and 2.21 vs. 1.43, P = 0.002 for that developed by Ibrahim et al.). On the contrary, lifetime ESRD risk was not significantly different between the two groups. At both times (15 years and lifetime), we observed a significant overlap of ESRD risk between the two groups. ESRD risk calculators could be complementary to standard screening strategy but cannot be used alone to accept or decline donation.


Assuntos
Falência Renal Crônica/etiologia , Transplante de Rim , Doadores Vivos , Nefrectomia/efeitos adversos , Adulto , Contraindicações de Procedimentos , Seleção do Doador , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Risco , Coleta de Tecidos e Órgãos/efeitos adversos , Obtenção de Tecidos e Órgãos
19.
Prehosp Emerg Care ; 21(3): 386-389, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28103127

RESUMO

INTRODUCTION: Extracorporeal Cardiopulmonary Resuscitation (ECPR) is now considered for the treatment of refractory cardiac arrest. CASE REPORT: In an urban city like Paris, extraction times of in-hospital ECPR can be long for patients presenting with refractory cardiac arrest. Using the medicalized prehospital system, we developed a possible early prehospital ECPR implementation. This case report is an example of ECPR prehospital implementation in the Louvre Museum. CONCLUSION: Patients eligible for ECPR must be selected according to strict criteria. Further research is necessary to compare prehospital and in-hospital implementation.


Assuntos
Reanimação Cardiopulmonar/métodos , Serviços Médicos de Emergência/métodos , Oxigenação por Membrana Extracorpórea/métodos , Parada Cardíaca Extra-Hospitalar/terapia , Idoso , Evolução Fatal , Humanos , Masculino , Museus , Fatores de Tempo , Transporte de Pacientes
20.
Eur Heart J ; 37(42): 3222-3228, 2016 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-26497161

RESUMO

AIMS: Survival after out-of-hospital cardiac arrest (OHCA) remains disappointingly low. Among patients admitted alive, early prognostication remains challenging. This study aims to establish a stratification score for patients admitted in intensive care unit (ICU) after OHCA, according to their neurological outcome. METHODS AND RESULTS: The CAHP (Cardiac Arrest Hospital Prognosis) score was developed from the Sudden Death Expertise Center registry (Paris, France). The primary outcome was poor neurological outcome defined as Cerebral Performance Category 3, 4, or 5 at hospital discharge. Independent prognostic factors were identified using logistic regression analysis and thresholds defined to stratify low-, moderate-, and high-risk groups. The CAHP score was validated in both a prospective and an external data set (Parisian Cardiac Arrest Registry). The developmental data set included 819 patients admitted from May 2011 to December 2012. After multivariate analysis, seven variables were independently associated with poor neurological outcome and subsequently included in the CAHP score (age, non-shockable rhythm, time from collapse to basic life support, time from basic life support to return of spontaneous circulation, location of cardiac arrest, epinephrine dose, and arterial pH). Three risks groups were identified: low risk (score ≤150, 39% of unfavourable outcome), medium risk (score 150-200, 81% of unfavourable outcome) and high-risk group (score ≥200, 100% of unfavourable outcome). The AUC of the CAHP score were 0.93, and the discrimination value in the validation data sets was consistent (respectively, AUC 0.91 and 0.85). CONCLUSION: The CAHP score represents a simple tool for early stratification of patients admitted in ICU after OHCA. A high-risk category of patients with very poor prognosis can be easily identified.


Assuntos
Parada Cardíaca Extra-Hospitalar , Reanimação Cardiopulmonar , França , Humanos , Paris , Prognóstico , Estudos Prospectivos
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