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1.
Anesth Analg ; 2024 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-38781094

RESUMO

BACKGROUND: The aim of this study was to assess temporal trends in incidence and underlying causes of maternal deaths from obstetric hemorrhage in France and to describe clinical care before and after implementation of the first national guidelines published in 2004 and updated in 2014. METHODS: Data from all hemorrhage-related maternal deaths between 2001 and 2015 were extracted from the French Confidential Enquiry into Maternal Deaths. We compared the maternal mortality ratio (MMR), cause of obstetric hemorrhage, and death preventability by triennium. Critical care, transfusion, and obstetric management among women who died were described for 2001 to 2003 and 2013 to 2015. RESULTS: The MMR from obstetric hemorrhage significantly decreased over time from 2.3 of 100,000 livebirths (54 of 2,391,551) in 2001 to 2003 to 0.8 of 100,000 livebirths (19 of 2,412,720) in 2013 to 2015. In 2001 to 2003, uterine atony accounted for 50% (27 of 54) of maternal deaths vs 21% (4 of 19) in 2013 to 2015. As compared to 2001 to 2003, an increased proportion of women had hemodynamic continuous monitoring in 2013 to 2015 (30%, 9 of 30, vs 47%, 8 of 18) and received vasopressor infusion therapy (57%, 17 of 30, vs 72%, 13 of 18), and a smaller proportion was extubated during active hemorrhage (17%, 5 of 30, vs 0 of 18). Transfusion therapy was initiated more frequently and earlier in 2013 to 2015 (71 vs 58 minutes). In 2013 to 2015, 88% of maternal deaths due to hemorrhage remained preventable. The main identified improvable care factors were related to delays in diagnosis and surgical management, particularly after cesarean delivery. CONCLUSIONS: Maternal mortality by obstetric hemorrhage decreased dramatically in France between 2001 and 2015, particularly mortality due to uterine atony. Among women who died, we detected fewer instances of substandard transfusion management or critical care. Nevertheless, opportunities for improvement were observed in most of the recent cases.

2.
Crit Care ; 27(1): 7, 2023 01 07.
Artigo em Inglês | MEDLINE | ID: mdl-36611211

RESUMO

BACKGROUND: Current guidelines suggest the introduction of early nutrition support within the first 48 h of admission to the intensive care unit (ICU) for patients who cannot eat. In that context, we aimed to describe nutrition practices in the ICU and study the association between the introduction of early nutrition support (< 48 h) in the ICU and patient mortality at day 28 (D28) using data from a multicentre prospective cohort. METHODS: The 'French-Speaking ICU Nutritional Survey' (FRANS) study was conducted in 26 ICUs in France and Belgium over 3 months in 2015. Adult patients with a predicted ICU length of stay > 3 days were consecutively included and followed for 10 days. Their mortality was assessed at D28. We investigated the association between early nutrition (< 48 h) and mortality at D28 using univariate and multivariate propensity-score-weighted logistic regression analyses. RESULTS: During the study period, 1206 patients were included. Early nutrition support was administered to 718 patients (59.5%), with 504 patients receiving enteral nutrition and 214 parenteral nutrition. Early nutrition was more frequently prescribed in the presence of multiple organ failure and less frequently in overweight and obese patients. Early nutrition was significantly associated with D28 mortality in the univariate analysis (crude odds ratio (OR) 1.69, 95% confidence interval (CI) 1.23-2.34) and propensity-weighted multivariate analysis (adjusted OR (aOR) 1.05, 95% CI 1.00-1.10). In subgroup analyses, this association was stronger in patients ≤ 65 years and with SOFA scores ≤ 8. Compared with no early nutrition, a significant association was found of D28 mortality with early enteral (aOR 1.06, 95% CI 1.01-1.11) but not early parenteral nutrition (aOR 1.04, 95% CI 0.98-1.11). CONCLUSIONS: In this prospective cohort study, early nutrition support in the ICU was significantly associated with increased mortality at D28, particularly in younger patients with less severe disease. Compared to no early nutrition, only early enteral nutrition appeared to be associated with increased mortality. Such findings are in contrast with current guidelines on the provision of early nutrition support in the ICU and may challenge our current practices, particularly concerning patients at low nutrition risk. Trial registration ClinicalTrials.gov Identifier: NCT02599948. Retrospectively registered on November 5th 2015.


Assuntos
Estado Terminal , Apoio Nutricional , Adulto , Humanos , Estudos Prospectivos , Estado Terminal/terapia , Estudos de Coortes , Estado Nutricional , Unidades de Terapia Intensiva , Tempo de Internação
3.
Am J Obstet Gynecol ; 226(6): 839.e1-839.e24, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-34914894

RESUMO

BACKGROUND: Placenta accreta spectrum is a life-threatening condition that has increased dramatically in recent decades along with cesarean rates worldwide. Cesarean hysterectomy is widely practiced in women with placenta accreta spectrum; however, the maternal outcomes after cesarean hysterectomy have not been thoroughly compared with the maternal outcomes after alternative approaches, such as conservative management. OBJECTIVE: This study aimed to compare the severe maternal outcomes between women with placenta accreta spectrum treated with cesarean hysterectomy and those treated with conservative management (leaving the placenta in situ). STUDY DESIGN: From a source population of 520,114 deliveries in 176 hospitals (PACCRETA study), we designed an observational cohort of women with placenta accreta spectrum who had either a cesarean hysterectomy or a conservative management (the placenta left in situ) during cesarean delivery. Clinicians prospectively identified women meeting the inclusion criteria and included them at delivery. Data collection started only after the women had received information and agreed to participate in the study in the immediate postpartum period. The primary outcome was the transfusion of >4 units of packed red blood cells within 6 months after delivery. Secondary outcomes were other maternal complications within 6 months. We used propensity score weighting to account for potential indication bias. RESULTS: Here, 86 women had conservative management and 62 women had cesarean hysterectomy for placenta accreta spectrum during cesarean delivery. The primary outcome occurred in 14 of 86 women in the conservative management group (16.3%) and 36 of 61 (59.0%) in the cesarean hysterectomy group (risk ratio in propensity score weighted model, 0.29; 95% confidence interval, 0.19-0.45). The rates of hysterectomy, total estimated blood loss exceeding 3000 mL, any blood product transfusion, adjacent organ injury, and nonpostpartum hemorrhage-related severe maternal morbidity were lower with conservative management than with cesarean hysterectomy (all adjusted, P≤.02); but, the rates of arterial embolization, endometritis, and readmission within 6 months of discharge were higher with conservative management than with cesarean hysterectomy. CONCLUSION: Among women with placenta accreta spectrum who underwent cesarean delivery, conservative management was associated with a lower risk of transfusion of >4 units of packed red blood cells within 6 months than cesarean hysterectomy.


Assuntos
Placenta Acreta , Cesárea , Tratamento Conservador , Feminino , Humanos , Histerectomia , Placenta Acreta/epidemiologia , Placenta Acreta/cirurgia , Gravidez , Estudos Prospectivos , Estudos Retrospectivos
4.
Paediatr Perinat Epidemiol ; 36(2): 171-180, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34964499

RESUMO

BACKGROUND: Severe maternal morbidity (SMM) is a key indicator of maternal health. Generally explored without distinction by the timing of the event, it mainly reflects postpartum SMM. Although antepartum (pre-labour) SMM presents specific challenges in its need to optimise the risk-benefit balance for both mother and foetus, its features remain inadequately explored. OBJECTIVES: We explored risk factors of antepartum SMM and described adverse delivery and neonatal outcomes associated with antepartum SMM. METHODS: We designed a population-based nested case-control study based on data from the EPIMOMS study (119 maternity hospitals of 6 French regions, 2012-2013, N = 182,309 deliveries in the source cohort). This study included all women with antepartum SMM (cases, n = 601) compared to a randomly selected sample of women who gave birth without SMM in the same hospitals (controls, n = 3651). Antepartum SMM risk factors were identified with multivariable logistic regression following imputations for missing data. RESULTS: Antepartum SMM complicated 0.33% (95% confidence interval [CI] 0.30, 0.36) of pregnancies. Antepartum SMM risk factors were maternal age ≥35 years (adjusted odds ratio [OR] 1.55, 95% CI 1.22, 1.97), increased body mass index (OR for 5 kg/m2 increase, 1.24, 95% CI 1.14, 1.36), maternal birth in sub-Saharan Africa (OR 1.80, 95% CI 1.29, 2.53), pre-existing medical condition (OR 2.56, 95% CI 1.99, 3.30), nulliparity (OR 2.26, 95% CI 1.83, 2.80), previous pregnancy-related hypertensive disorders (OR 4.94, 95% CI 3.36, 7.26), multiple pregnancy (OR 5.79, 95% CI 3.75, 7.26), irregular prenatal care (OR 1.86, 95% CI 1.27, 2.72). For women with antepartum SMM, preterm delivery, neonatal mortality and transfer to the neonatal intensive care unit were 10 times more frequent than for controls. Emergency caesarean and general anaesthesia were more frequent in women with antepartum SMM. CONCLUSIONS: Antepartum SMM is rare but associated with increased rates of adverse delivery and neonatal outcomes.


Assuntos
Complicações na Gravidez , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Recém-Nascido , Idade Materna , Gravidez , Complicações na Gravidez/etiologia , Gravidez Múltipla , Fatores de Risco
5.
Anesth Analg ; 134(3): 581-591, 2022 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-33989204

RESUMO

BACKGROUND: Severe acute maternal morbidity (SAMM) accounts for any life-threatening complication during pregnancy or after delivery. Measuring and monitoring SAMM seem critical to assessing the quality of maternal health care. The objectives were to explore the validity of intensive care unit (ICU) admission as an indicator of SAMM by characterizing the profile of women admitted to an ICU and of their ICU stay, according to the association with other SAMM criterion. METHODS: We performed a secondary analysis of the 2540 women with SAMM included in the epidemiology of severe acute maternal morbidity (EPIMOMS) multiregional prospective population-based study (2012-2013, n = 182,309 deliveries). The EPIMOMS definition of SAMM, based on national experts' consensus, is a combination of diagnosis, organ dysfunctions, and intervention criteria, including ICU admission. Among women with SAMM, we identified characteristics associated with maternal ICU admission with or with no other SAMM criterion compared with ICU admission, by using multivariable multinomial logistic regression models. RESULTS: Overall, 511 women were admitted to an ICU during or up to 42 days after pregnancy, for a population-based rate of 2.8 of 1000 deliveries (511/182,309; 95% confidence interval [CI], 2.6-3.1); 15.5% of them (79/511; 95% CI, 12.4-18.9) had no other SAMM criterion compared with ICU admission. Among women with SAMM, the odds of ICU admission with no other morbidity criterion were increased in women with preexisting medical conditions (adjusted odds ratio (aOR), 2.13; 95% CI, 1.17-3.86) and cesarean before labor (aOR, 3.12; 95% CI, 1.47-6.64). Women admitted to ICU with no other SAMM criterion had more often decompensation of a preexisting condition, no interventions for organ support, and a shorter length of stay than women admitted with other SAMM criteria. CONCLUSIONS: Among women with SAMM, 1 in 5 is admitted to an ICU; 15.5% of those admitted in ICU have no other SAMM criterion and a less acute condition. These results challenge the use of ICU admission as a criterion of SAMM.


Assuntos
Unidades de Terapia Intensiva/estatística & dados numéricos , Admissão do Paciente/estatística & dados numéricos , Complicações na Gravidez/epidemiologia , Adulto , Cesárea , Feminino , Humanos , Tempo de Internação , Serviços de Saúde Materna , População , Cobertura de Condição Pré-Existente , Gravidez , Complicações na Gravidez/terapia , Estudos Prospectivos , Estados Unidos/epidemiologia
6.
Eur J Anaesthesiol ; 39(6): 489-497, 2022 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-35608876

RESUMO

BACKGROUND: Disparities in access to pain management have been identified in several care settings, such as emergency departments and intensive care units, but with regard to labour analgesia, it remains poorly explored. OBJECTIVES: To determine the proportion of women without pain management during labour and its individual and organisational determinants. DESIGN: Secondary analysis of a nationwide cross-sectional population-based study, the 2016 French National Perinatal Survey. SETTINGS: All maternity units in France. PARTICIPANTS: Ten thousand and eleven women who attempted vaginal delivery with a labour duration at least 15 min. MAIN OUTCOME MEASURE: Absence of pain management, defined as absence of any pharmacological or nonpharmacological analgesic method during labour. RESULTS: Among the 10 011 women included, 542 (5.4%) had no labour pain management: 318 (3.7%) of the 8526 women who initially preferred to use neuraxial analgesia and 222 (15.8%) of the 1402 who did not. Using generalised estimating equations stratified according to the maternal antenatal preference for neuraxial analgesia, the common determinants of no labour pain management in both groups were no attendance at childbirth education classes and admission to a delivery unit during the night. Among women who initially preferred to use neuraxial analgesia, those who delivered in units with <1500 annual deliveries compared with units with 2000 to 3499 annual deliveries, were more likely to do without pain management [adjusted odds ratio (OR) = 1.96; 95% confidence interval (CI), 1.39 to 2.78]; among those who did not prefer to use it, women born abroad were more likely to do without labour pain management (adjusted OR = 1.64; 95% CI, 1.12 to 2.40). CONCLUSION: In France, 1 : 20 women had no labour pain management, and this proportion was three times higher among women who preferred not to use neuraxial analgesia. Enhancing maternal information on labour pain and its management, especially nonpharmacological methods, and rethinking care organisation, could improve access to analgesia of any kind.


Assuntos
Analgesia Obstétrica , Dor do Parto , Trabalho de Parto , Analgesia Obstétrica/métodos , Estudos Transversais , Feminino , Humanos , Dor do Parto/diagnóstico , Dor do Parto/epidemiologia , Dor do Parto/terapia , Manejo da Dor/métodos , Gravidez
7.
J Endovasc Ther ; 28(3): 415-424, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33660577

RESUMO

PURPOSE: Evaluate the impact of hybrid operating room (HOR) guidance on the long-term clinical outcomes following fenestrated and branched endovascular repair (F-BEVAR) for complex aortic aneurysms. MATERIALS AND METHODS: Prospectively collected registry data were retrospectively analyzed to compare the procedural, short- and long-term outcomes of consecutive F-BEVAR performed from January 2010 to December 2014 under standard mobile C-arm versus hybrid room guidance in a high-volume aortic center. RESULTS: A total of 262 consecutive patients, including 133 patients treated with a mobile C-arm equipped operating room and 129 with a HOR guidance, were enrolled in this study. Patient radiation exposure and contrast media volume were significantly reduced in the HOR group. Short-term clinical outcomes were improved despite higher case complexity in the HOR group, with no statistical significance. At a median follow-up of 63.3 months (Q1 33.4, Q3 75.9) in the C-arm group, and 44.9 months (Q1 25.1, Q3 53.5, p=0.53) in the HOR group, there was no statistically significant difference in terms of target vessel occlusion and limb occlusion. When the endograft involved 3 or more fenestrations and/or branches (complex F-BEVAR), graft instability (36% vs 25%, p=0.035), reintervention on target vessels (20% vs 11%, p=0.019) and total reintervention rates (24% vs 15%, p=0.032) were significantly reduced in the HOR group. The multivariable Cox regression analysis did not show statistically significant differences for long-term death and aortic-related death between the 2 groups. CONCLUSION: Our study suggests that better long-term clinical outcomes could be observed when performing complex F-BEVAR in the latest generation HOR.


Assuntos
Aneurisma da Aorta Abdominal , Implante de Prótese Vascular , Procedimentos Endovasculares , Aneurisma da Aorta Abdominal/diagnóstico por imagem , Aneurisma da Aorta Abdominal/cirurgia , Prótese Vascular , Implante de Prótese Vascular/efeitos adversos , Procedimentos Endovasculares/efeitos adversos , Humanos , Salas Cirúrgicas , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento
8.
Br J Anaesth ; 127(6): 942-952, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34511258

RESUMO

BACKGROUND: Disparities in neuraxial analgesia use for childbirth by maternal origin have been reported in high-resource countries. We explored the association between maternal immigrant status (characterised separately by geographic continental origin and Human Development Index [HDI] of maternal country of birth) and neuraxial analgesia use. We hypothesised that immigrant women from low-resource countries may have more limited access to neuraxial analgesia than native French women. METHODS: The study population, extracted from the 2016 National Perinatal Survey, a cross-sectional study of a representative sample of births in France, included only women who initially wished to deliver with neuraxial analgesia. We used multivariable multilevel logistic regression to explore the association between immigrant status and both use of neuraxial analgesia and its timely administration. RESULTS: Among the 6070 women included, 88.1% gave birth with neuraxial analgesia and 15.8% were immigrants. There was no difference in neuraxial analgesia use between native French women and either immigrant women by geographic continental region of origin, or immigrants from countries with low HDI. However, immigrants from countries with very high HDI were more likely to give birth with neuraxial analgesia (adjusted odds ratio [aOR]=2.6; 95% confidence interval (CI), 1.2-5.8; P=0.018) and its timeliness <60 min after admission (aOR=1.8; 95% CI, 1.2-2.7; P=0.005) compared with native French women. CONCLUSIONS: In France, immigrant women from low-resource countries have similar access to labour neuraxial analgesia to native French women. Our results suggest differential neuraxial analgesia use in favour of immigrant women from very high HDI countries compared with native women.


Assuntos
Analgesia Epidural/métodos , Analgesia Obstétrica/métodos , Emigrantes e Imigrantes/estatística & dados numéricos , Disparidades em Assistência à Saúde/estatística & dados numéricos , Trabalho de Parto , Manejo da Dor/métodos , Adulto , Estudos Transversais , Países em Desenvolvimento , Emigração e Imigração , Feminino , França , Humanos , Gravidez , Estudos Retrospectivos
9.
Br J Anaesth ; 125(1): e81-e87, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32303378

RESUMO

BACKGROUND: Pregnant women are at increased risk of hypoxaemia during general anaesthesia. Our aim was to determine the incidence and the risk factors that contribute to hypoxaemia in this setting. METHODS: Every woman 18 yr or older who underwent a non-elective Caesarean section under general anaesthesia was eligible to participate in this multicentre observational study. The primary endpoint was the incidence of hypoxaemia defined as the SpO2 ≤95%. The secondary endpoint was the incidence of difficult intubation defined as more than two attempts or failed intubation. RESULTS: During the study period, 895 women were prospectively included in 17 maternity hospitals, accounting for 79% of women who had general anaesthesia for non-elective Caesarean section. Maternal hypoxaemia was observed in 172 women (19%; confidence interval [CI], 17-22%). Risk factors associated with hypoxaemia in the multivariate analysis were difficult or failed intubation (adjusted odds ratio [aOR]=19.1 [8.6-42.7], P<0.0001) and BMI >35 kg m-2 (aOR=0.53 [0.28-0.998], P=0.0495). Intubation was difficult in 40 women (4.5%; CI, 3.3-6%) and failed intubation occurred in five women (0.56%; CI, 0.1-1%). In the multivariate analysis, use of a hypnotic drug other than propofol was associated with difficult or failed intubation (aOR=25 [2-391], P=0.02). A propensity score confirmed that propofol was associated with a significant decreased risk of difficulty or failure to intubate (P<0.001). CONCLUSIONS: Hypoxaemia during Caesarean sections was observed in 19% of women and was significantly associated with difficult or failed intubation. The use of propofol may protect against the occurrence of difficult intubation.


Assuntos
Anestesia Geral/efeitos adversos , Anestesia Obstétrica/efeitos adversos , Cesárea , Hipóxia/epidemiologia , Mães , Adulto , Anestesia Geral/métodos , Anestesia Obstétrica/métodos , Feminino , França/epidemiologia , Humanos , Incidência , Intubação Intratraqueal , Gravidez , Estudos Prospectivos , Fatores de Risco
10.
Anesth Analg ; 130(1): 52-62, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31283618

RESUMO

BACKGROUND: The variability in resources for managing critical events among maternity hospitals may impact maternal safety. Our main objective was to assess the risk of postpartum maternal death according to hospitals' organizational characteristics. A secondary objective aimed to assess the specific risk of death due to postpartum hemorrhage (PPH). METHODS: This national population-based case-control study included all 2007-2009 postpartum maternal deaths from the national confidential enquiry (n = 147 cases) and a 2010 national representative sample of parturients (n = 14,639 controls). To adjust for referral bias, cases were classified by time when the condition/complication responsible for the death occurred: postpartum maternal deaths due to conditions present before delivery (n = 66) or during or after delivery (n = 81). Characteristics of delivery hospitals included 24/7 on-site availability of an anesthesiologist and an obstetrician, level of perinatal care, number of deliveries annually, and their teaching and profit status. In teaching and other nonprofit hospitals in France, obstetric care is organized on the principle of collective team-based management, while in for-profit hospitals, this organization is based mostly on that of "one woman-one doctor." Logistic regression models were used to estimate adjusted odds ratios (aORs) and 95% confidence intervals (CIs) for postpartum maternal death. RESULTS: The risk of maternal death from prepartum conditions was lower for women who gave birth in for-profit compared with teaching hospitals (aOR, 0.3; 95% CI, 0.1-0.8; P = .02) and in hospitals with <1500 vs ≥1500 annual deliveries (aOR, 0.4; 95% CI, 0.1-0.9; P = .02). Conversely, the risk of postpartum maternal death from complications occurring during or after delivery was higher for women who delivered in for-profit compared with teaching hospitals (aOR, 2.8; 95% CI, 1.3-6.0; P = .009), as was the risk of death from PPH in for-profit versus nonprofit hospitals (aOR, 2.8; 95% CI, 1.2-6.5; P = .019). CONCLUSIONS: After adjustment for the referral bias related to prepartum morbidity, the risk of postpartum maternal mortality in France differs according to the hospital's organizational characteristics.


Assuntos
Disparidades em Assistência à Saúde/tendências , Administração Hospitalar/tendências , Hospitais/tendências , Mortalidade Materna/tendências , Parto , Hemorragia Pós-Parto/mortalidade , Período Pós-Parto , Padrões de Prática Médica/tendências , Adulto , Estudos de Casos e Controles , Feminino , França/epidemiologia , Humanos , Hemorragia Pós-Parto/diagnóstico , Hemorragia Pós-Parto/terapia , Prognóstico , Medição de Risco , Fatores de Risco , Fatores de Tempo
11.
Biochem Biophys Res Commun ; 503(3): 1861-1867, 2018 09 10.
Artigo em Inglês | MEDLINE | ID: mdl-30057314

RESUMO

Despite the major success obtained by the use of tyrosine kinase inhibitors (TKI) in chronic myeloid leukemia (CML), resistances to therapies occur due to mutations in the ABL-kinase domain of the BCR-ABL oncogene. Amongst these mutations, the "gatekeeper" T315I is a major concern as it renders leukemic cells resistant to all licenced TKI except Ponatinib. We report here that Fourier transform infrared (FTIR) microspectroscopy is a powerful methodology allowing rapid and direct identification of a spectral signature in single cells expressing T315I-mutated BCR-ABL. The specificity of this spectral signature is confirmed using a Dox-inducible T315I-mutated BCR-ABL-expressing human UT-7 cells as well as in murine embryonic stem cells. Transcriptome analysis of UT-7 cells expressing BCR-ABL as compared to BCR-ABL T315I clearly identified a molecular signature which could be at the origin of the generation of metabolic changes giving rise to the spectral signature. Thus, these results suggest that this new methodology can be applied to the identification of leukemic cells harbouring the T315I mutation at the single cell level and could represent a novel early detection tool of mutant clones. It could also be applied to drug screening strategies to target T315I-mutated leukemic cells.


Assuntos
Proteínas de Fusão bcr-abl/metabolismo , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Espectroscopia de Infravermelho com Transformada de Fourier , Animais , Linhagem Celular , Proteínas de Fusão bcr-abl/genética , Humanos , Leucemia Mielogênica Crônica BCR-ABL Positiva/metabolismo , Leucemia Mielogênica Crônica BCR-ABL Positiva/patologia , Camundongos , Mutação
12.
Biochem Biophys Res Commun ; 498(4): 715-722, 2018 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-29550484

RESUMO

Manganese Superoxide dismutase 2 (SOD2) plays a crucial role in antioxidant defense but there are no data suggesting its role in genetic instability in CML. We evaluated the effects of SOD2 silencing in human UT7 cell line expressing either non-mutated or T315I-mutated BCR-ABL. Array-CGH experiments detected in BCR-ABL-expressing cells silenced for SOD2 a major genetic instability within several chromosomal loci, especially in regions carrying the glypican family (duplicated) and ß-defensin genes (deleted). In a large cohort of patients with chronic myeloid leukemia (CML), a significant decrease of SOD2 mRNA was observed. This reduction appeared inversely correlated with leukocytosis and Sokal score, high-risk patients showing lower SOD2 levels. The analysis of anti-oxidant gene expression analysis revealed a specific down-regulation of the expression of PRDX2 in UT7-BCR-ABL and UT7-T315I cells silenced for SOD2 expression. Gene set enrichment analysis performed between the two SOD2-dependent classes of CML patients revealed a significant enrichment of Reactive Oxygen Species (ROS) Pathway. Our data provide the first evidence for a link between SOD2 expression and genetic instability in CML. Consequently, SOD2 mRNA levels should be analyzed in prospective studies as patients with low SOD2 expression could be more prone to develop a mutator phenotype under TKI therapies.


Assuntos
Proteínas de Fusão bcr-abl/genética , Regulação Leucêmica da Expressão Gênica , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Superóxido Dismutase/genética , Linhagem Celular Tumoral , Estudos de Coortes , Inativação Gênica , Humanos , Mutação , Peroxirredoxinas/genética , Mutação Puntual
13.
Am J Obstet Gynecol ; 219(2): 193.e1-193.e9, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29733839

RESUMO

BACKGROUND: Abnormally invasive placentation is the leading cause of obstetric hysterectomy and can cause poor to disastrous maternal outcomes. Most previous studies of peripartum management and maternal morbidity have included variable proportions of severe and less severe cases. OBJECTIVE: The aim of this study was to compare maternal morbidity from placenta percreta and accreta. STUDY DESIGN: This retrospective study at a referral center in Paris includes all women with abnormally invasive placentation from 2003 through 2017. Placenta percreta and accreta were diagnosed histologically or clinically. When placenta percreta was suspected before birth, a conservative approach leaving the placenta in situ was proposed because of the intraoperative risk of cesarean delivery. When placenta accreta was suspected, parents were offered a choice of a conservative approach or an attempt to remove the placenta, to be followed in case of failure by hysterectomy. Maternal outcomes were compared between women with placenta percreta and those with placenta accreta/increta. The primary outcome measure was a composite criterion of severe acute maternal morbidity including at least 1 of the following: hysterectomy during cesarean delivery, delayed hysterectomy, transfusion of ≥10 U of packed red blood cells, septic shock, acute kidney injury, cardiovascular failure, maternal transfer to intensive care, or death. RESULTS: Of the 156 women included, 51 had placenta percreta and 105 placenta accreta. Abnormally invasive placentation was suspected antenatally nearly 4 times more frequently in the percreta than the accreta group (96.1% [49/51] vs 25.7% [27/105], P < .01). Among the 76 women with antenatally suspected abnormally invasive placentation (48.7%), the rate of antenatal decisions for conservative management was higher in the percreta than the accreta group (100% [49/49] vs 40.7% [11/27], P < .01). The composite maternal morbidity rate was significantly higher in the percreta than the accreta group (86.3% [44/51] vs 28/105 [26.7%], P < .001). A secondary analysis restricted to women with an abnormally invasive placentation diameter >6 cm showed similar results (86.0% [43/50) vs 48.7% [19/38), P < .01). The rate of hysterectomy during cesareans was significantly higher in the percreta than the accreta group (52.9% [27/51] vs 20.9% [22/105], P < .01) as was the total hysterectomy rate (43/51 [84.3%] vs 23.8% [25/105], P < .01). CONCLUSION: Severe maternal morbidity is much more frequent in women with placenta percreta than with placenta accreta, despite multidisciplinary planning, management in a referral center, and better antenatal suspicion.


Assuntos
Injúria Renal Aguda/epidemiologia , Cesárea , Tratamento Conservador , Transfusão de Eritrócitos/estatística & dados numéricos , Histerectomia/estatística & dados numéricos , Morte Materna/estatística & dados numéricos , Placenta Acreta/terapia , Hemorragia Pós-Parto/terapia , Choque Séptico/epidemiologia , Adulto , Índice de Apgar , Peso ao Nascer , Estudos de Coortes , Feminino , França , Humanos , Recém-Nascido , Unidades de Terapia Intensiva/estatística & dados numéricos , Unidades de Terapia Intensiva Neonatal/estatística & dados numéricos , Imageamento por Ressonância Magnética , Placenta Acreta/diagnóstico , Gravidez , Estudos Retrospectivos , Ultrassonografia Pré-Natal
15.
Phys Chem Chem Phys ; 20(33): 21474-21486, 2018 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-30088499

RESUMO

8-Hydroxyquinoline (8HQ) is a new green corrosion inhibitor. DFT-D calculations are performed to investigate the adsorption of 8HQ and derivatives on the Al(111) surface from low to high coverage. From θ = 0.20 to 0.66, the adsorption energies are -1.12, -2.41, -1.66 and -3.44 eV per molecule for 8HQ, and its tautomer, its hydrogenated and its dehydrogenated species, independently of the coverage. In contrast, the geometry of the adsorbates changes between coverage up to 0.66 and the full monolayer (θ = 1). The creation of a dipole at the molecule/metal interface reduces the work function of aluminum. To further evaluate the modification of the reactivity of the surface, adsorption of O2 on the Al(111) surface covered by the organic layer is investigated. O2 dissociation takes place for θ = 0.66. When the Al surface is fully covered (θ = 1), the reduction of O2 and the oxidation of Al atoms do not occur.

16.
Anesth Analg ; 126(1): 175-182, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-28961562

RESUMO

BACKGROUND: A structured definition of amniotic fluid embolism (AFE) based on 4 criteria was recently proposed for use in research by the Society for Maternal-Fetal Medicine (SMFM) and the Amniotic Fluid Embolism Foundation. The main objective of this study was to review all AFE-related maternal deaths in France during 2007-2011 according to the presence or not of all these 4 diagnostic criteria. METHODS: Maternal deaths due to AFE were identified by the national experts committee of the French Confidential Enquiry into Maternal Deaths during 2007-2011 (n = 39). The maternal mortality ratio for AFE was calculated. We applied the structured definition proposed by the Society for Maternal-Fetal Medicine and the Amniotic Fluid Embolism Foundation to AFE-related maternal deaths identified by the national experts committee. Characteristics of women, pregnancies and deliveries; clinical and biological features of AFE; and specific laboratory tests used were described by the presence or not of all 4 diagnostic criteria. Management of obstetric hemorrhage and quality of care according to the experts were also described. RESULTS: The maternal mortality ratio from AFE was 0.95/100,000 live births (95% confidence interval, 0.67-1.3). Detailed clinical data were collected for 36 women who died from AFE: 21 (58%) had all 4 proposed diagnostic criteria and 15 (42%) had 1 or more missing criterion. Documented early disseminated intravascular coagulopathy was missing for 14 women, and 2 women exhibited more than 1 missing criterion. Ten of the 15 women with missing criteria had clinical coagulopathy, with standard hemostasis tests performed in only 3. Specific diagnostic examinations for AFE were performed in similar proportions by the presence or not of all diagnostic criteria. Opportunities to improve care included timely performance of indicated hysterectomy (n = 13) and improved transfusion practices (n = 9). In the context of maternal cardiac arrest, for 5 of 13 women, fetal extraction was performed within 5 minutes. CONCLUSIONS: The structured definition of AFE for research studies would exclude more than one-third of AFE-related maternal deaths identified by the national experts committee. Inclusion of clinical coagulopathy as a diagnostic criterion for AFE would reduce this proportion to 14%. There is still room for improvement in the management of obstetric hemorrhage and timely fetal extraction in the context of maternal cardiac arrest, frequently observed in AFE-related maternal death.


Assuntos
Embolia Amniótica/mortalidade , Embolia Amniótica/prevenção & controle , Morte Materna/prevenção & controle , Adulto , Embolia Amniótica/diagnóstico , Feminino , França/epidemiologia , Humanos , Gravidez , Fatores de Risco
17.
Nucleic Acids Res ; 42(9): 5616-32, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24598253

RESUMO

The repair of toxic double-strand breaks (DSB) is critical for the maintenance of genome integrity. The major mechanisms that cope with DSB are: homologous recombination (HR) and classical or alternative nonhomologous end joining (C-NHEJ versus A-EJ). Because these pathways compete for the repair of DSB, the choice of the appropriate repair pathway is pivotal. Among the mechanisms that influence this choice, deoxyribonucleic acid (DNA) end resection plays a critical role by driving cells to HR, while accurate C-NHEJ is suppressed. Furthermore, end resection promotes error-prone A-EJ. Increasing evidence define Poly(ADP-ribose) polymerase 3 (PARP3, also known as ARTD3) as an important player in cellular response to DSB. In this work, we reveal a specific feature of PARP3 that together with Ku80 limits DNA end resection and thereby helps in making the choice between HR and NHEJ pathways. PARP3 interacts with and PARylates Ku70/Ku80. The depletion of PARP3 impairs the recruitment of YFP-Ku80 to laser-induced DNA damage sites and induces an imbalance between BRCA1 and 53BP1. Both events result in compromised accurate C-NHEJ and a concomitant increase in DNA end resection. Nevertheless, HR is significantly reduced upon PARP3 silencing while the enhanced end resection causes mutagenic deletions during A-EJ. As a result, the absence of PARP3 confers hypersensitivity to anti-tumoral drugs generating DSB.


Assuntos
Proteínas de Ciclo Celular/fisiologia , Reparo do DNA por Junção de Extremidades , Poli(ADP-Ribose) Polimerases/fisiologia , Reparo de DNA por Recombinação , Antígenos Nucleares/metabolismo , Antineoplásicos/farmacologia , Proteína BRCA1/metabolismo , Linhagem Celular Tumoral , Quebras de DNA de Cadeia Dupla , DNA Helicases/metabolismo , Proteínas de Ligação a DNA/metabolismo , Ensaios de Seleção de Medicamentos Antitumorais , Etoposídeo/farmacologia , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Autoantígeno Ku , Proteínas Nucleares/metabolismo , Processamento de Proteína Pós-Traducional , Transporte Proteico , Proteína de Replicação A/metabolismo , Proteína 1 de Ligação à Proteína Supressora de Tumor p53
18.
Crit Care Med ; 43(1): 78-86, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25377016

RESUMO

OBJECTIVE: To determine the national rate per delivery of pregnancy-related ICU admissions of women in France, the characteristics and severity of these cases, and their trends over the 4-year study period. DESIGN: Descriptive study from the national hospital discharge database. SETTING: All ICUs in France. PATIENTS: All women admitted to an ICU during the pregnancy, the delivery, or the postpartum period from January 1, 2006, to December 31, 2009. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of 3,262,526 deliveries, 11,824 women had pregnancy-related ICU admissions, for an overall rate of 3.6 per 1,000 deliveries. The conditions reported most frequently were obstetric hemorrhages (34.2%) and hypertensive disorders of pregnancy (22.3%). Case severity was assessed with four markers: case-fatality rate (1.3%), length of ICU stay (mean, 3.0 ± 0.1 d), Simplified Acute Physiology Score II score (mean: 19.7 ± 0.1), and a SUP REA code, which indicates the combination of a Simplified Acute Physiology Score II score more than or equal to 15 and at least one specific procedure related to life support or organ failure (23.0%). The most frequent causes of ICU admission were those associated with the least severity in the ICU. During the study period, the rate of pregnancy-related ICU admissions decreased from 3.9 to 3.4 per 1,000 deliveries (p < 0.001), whereas the overall severity of cases increased with longer stays, higher Simplified Acute Physiology Score II scores, and a greater proportion of SUP REA codes (all p < 0.001). Analysis by principal diagnosis showed that the severity of the condition of women admitted to ICU significantly increased over time for hemorrhages and hypertensive complications. CONCLUSIONS: The rate of women with pregnancy-related ICU admissions decreased and the severity of their cases increased. Most ICU admissions remained related to the least severe conditions. This raises the issue of the most appropriate organization of care for women with pregnancy-related conditions who require continuous surveillance but not necessarily intensive care.


Assuntos
Unidades de Terapia Intensiva/estatística & dados numéricos , Complicações na Gravidez/epidemiologia , APACHE , Adulto , Parto Obstétrico/estatística & dados numéricos , Feminino , França/epidemiologia , Hospitalização/estatística & dados numéricos , Humanos , Hipertensão/complicações , Hipertensão/epidemiologia , Tempo de Internação/estatística & dados numéricos , Hemorragia Pós-Parto/epidemiologia , Gravidez , Complicações Cardiovasculares na Gravidez/epidemiologia , Proibitinas
19.
Anesth Analg ; 121(3): 759-766, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26086620

RESUMO

BACKGROUND: The rate of neuraxial analgesia during labor in France is one of the highest among high-income countries: 77% of vaginal deliveries in 2010. In this context, the question of how women's preferences for delivering without neuraxial analgesia relate to actual use is of interest. Our objective was to study the factors associated with women's initial preference for labor without neuraxial analgesia and those associated with its use in women who initially preferred not to have it. METHODS: We used data from the 2010 French National Perinatal Survey, a cross-sectional study of a representative sample of all births in France. Data were collected from interviews with mothers in the postpartum ward and from medical records. Our sample included 7123 women who had vaginal deliveries and were at low risk for cesarean delivery. The factors analyzed were maternal sociodemographic characteristics, prenatal care, childbirth class attendance, labor management, and organization of maternity units. Multilevel Poisson regression models were used to study factors associated with women's initial preference in the overall population and to study factors associated with actual use of neuraxial analgesia in the group of women who initially preferred not to have it. RESULTS: Initially, 26% of our population (n = 1835) preferred to deliver without neuraxial analgesia; this preference was associated with high parity, unfavorable social conditions, and delivery in a public maternity unit. Among these women, 52% (n = 961) delivered with neuraxial analgesia. This discrepancy between initial preference and actual use was significantly associated with nulliparity (adjusted relative risk [aRR] = 1.4; 95% confidence interval [CI], 1.3-1.6), oxytocin augmentation of labor (aRR = 2.4; 95% CI, 2.1-2.7), presence of an anesthesiologist in the unit 24/7 (aRR = 1.4; 95% CI, 1.2-1.6; compared with delivery in hospitals without an anesthesiologist on site 24/7), and high midwife workload (aRR = 1.1; 95% CI, 1.0-1.2). There was no clear association with maternal educational level. CONCLUSIONS: Our results suggest that parity, the management of labor, and availability of anesthesiologists play a major role in the intrapartum decision to use neuraxial analgesia for women who initially preferred not to have it. Further research is necessary in the clinical circumstances leading to this decision and the role of women's demands and medical staff attitudes throughout labor.


Assuntos
Analgesia Obstétrica/psicologia , Analgesia Obstétrica/estatística & dados numéricos , Coleta de Dados , Dor do Parto/psicologia , Trabalho de Parto/psicologia , Participação do Paciente/psicologia , Adulto , Estudos Transversais , Coleta de Dados/métodos , Feminino , França/epidemiologia , Humanos , Dor do Parto/epidemiologia , Dor do Parto/terapia , Manejo da Dor/métodos , Manejo da Dor/psicologia , Gravidez , Adulto Jovem
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