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Because low back pain is frequently a result of intervertebral disc degeneration (IVDD), strategies to regenerate or repair the IVD are currently being investigated. Often, ex vivo disc cultures of non-human IVD organs or tissue explants are used that usually do not exhibit natural IVDD. Therefore, degenerative changes mimicking those reported in human IVDD need to be induced. To support researchers in selecting ex vivo disc cultures, a systematic search was performed for them and their potential use for studying human IVDD reviewed. Five degeneration induction categories (proinflammatory cytokines, injury/damage, degenerative loading, enzyme, and other) were identified in 129 studies across 7 species. Methods to induce degeneration are diverse and can induce mild to severe degenerative changes that progress over time, as described for human IVDD. The induced degenerative changes are model-specific and there is no "one-fits-all" IVDD induction method. Nevertheless, specific aspects of human IVDD can be well mimicked. Currently, spontaneously degenerated disc cultures from large animals capture human IVDD in most aspects. Combinatorial approaches of several induction methods using discs derived from large animals are promising to recapitulate pathological changes on several levels, such as cellular behaviour, extracellular matrix composition, and biomechanical function, and therefore better mimic human IVDD. Future disc culture setups might increase in complexity, and mimic human IVDD even better. As ex vivo disc cultures have the potential to reduce and even replace animal trials, especially during preclinical development, advancement of such models is highly relevant for more efficient and cost-effective clinical translation from bench-to-bedside.
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Degeneração do Disco Intervertebral , Disco Intervertebral , Animais , Disco Intervertebral/patologia , Degeneração do Disco Intervertebral/patologia , Citocinas , Matriz ExtracelularRESUMO
Despite the known association of chronic cardiovascular diseases and more severe courses of COVID-19, little is known about individual risk perception of patients with a history of acute myocardial infarction (AMI) and resulting preventive behaviours. In May 2020, a postal survey was conducted, including 150 patients with previous AMI from the myocardial infarction registry Augsburg. The study objective was to assess COVID-19 knowledge, individual risk perception, worries, infection likelihood and preventive behaviours in this patient cohort. From the 100 respondents, 69.7% perceived themselves to be at high risk of developing a severe course of COVID-19. There was a significant positive correlation between dangerousness assessment and knowledge on COVID-19. Despite a majority (70%) of patients rating their susceptibility for an infection as moderate to very high, the individual likelihood of being infected was rated at only 3%. Almost 70% of patients with previous MI classified themselves at high risk for a severe course of COVID-19 infection. As seen in other risk groups as well, the availability of valuable information sources as well as the support in individual risk reduction strategies and psychological coping mechanisms are mandatory, especially since higher knowledge correlates with dangerousness assessment and might lead to better compliance with preventive behaviours.
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BACKGROUND: The aim of this study was to investigate the association between inflammatory markers and 28-day mortality in patients with ST-elevation myocardial infarction (STEMI). METHODS: In 398 STEMI patients recorded between 2009 and 2013 by the population-based Myocardial Infarction Registry Augsburg, 92 protein biomarkers were measured in admission arterial blood samples using the OLINK inflammatory panel. In multivariable-adjusted logistic regression models, the association between each marker and 28-day mortality was investigated. The values of the biomarkers most significantly associated with mortality were standardized and summarized to obtain a prediction score for 28-day mortality. The predictive ability of this biomarker score was compared to the established GRACE score using ROC analysis. Finally, a combined total score was generated by adding the standardized biomarker score to the standardized GRACE score. RESULTS: The markers IL-6, IL-8, IL-10, FGF-21, FGF-23, ST1A1, MCP-1, 4E-BP1, and CST5 were most significantly associated with 28-day mortality, each with FDR-adjusted (false discovery rate adjusted) p-values of < 0.01 in the multivariable logistic regression model. In a ROC analysis, the biomarker score and the GRACE score showed comparable predictive ability for 28-day mortality (biomarker score AUC: 0.7859 [CI: 0.6735-0.89], GRACE score AUC: 0.7961 [CI: 0.6965-0.8802]). By combining the biomarker score and the Grace score, the predictive ability improved with an AUC of 0.8305 [CI: 0.7269-0.9187]. A continuous Net Reclassification Improvement (cNRI) of 0.566 (CI: 0.192-0.94, p-value: 0.003) and an Integrated Discrimination Improvement (IDI) of 0.083 ((CI: 0.016-0.149, p-value: 0.015) confirmed the superiority of the combined score over the GARCE score. CONCLUSIONS: Inflammatory biomarkers may play a significant role in the pathophysiology of acute myocardial infarction (AMI) and AMI-related mortality and might be a promising starting point for personalized medicine, which aims to provide each patient with tailored therapy.
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Infarto do Miocárdio , Infarto do Miocárdio com Supradesnível do Segmento ST , Biomarcadores , Proteínas Sanguíneas , Humanos , Interleucina-10 , Interleucina-6 , Interleucina-8 , Valor Preditivo dos Testes , Prognóstico , Medição de Risco , Fatores de RiscoRESUMO
OBJECTIVE: To assess, according to chorionicity, the perinatal outcome of twin pregnancy in which vaginal delivery is planned. METHODS: JUMODA (JUmeaux MODe d'Accouchement) was a national prospective population-based cohort study of twin pregnancies, delivered in 176 maternity units in France, from February 2014 to March 2015. In this planned secondary analysis, we assessed, according to chorionicity, the perinatal outcome of twin pregnancies, in which vaginal delivery was planned, that delivered at or after 32 weeks of gestation with the first twin in cephalic presentation. In order to select a population with well-recognized indications for planned vaginal delivery, we applied the same exclusion criteria as those in the Twin Birth Study, an international randomized trial. Monochorionic twin pregnancies with twin-to-twin transfusion syndrome or twin anemia-polycythemia sequence were defined as complicated and were excluded. The primary outcome was a composite of intrapartum mortality and neonatal morbidity and mortality. Multivariable logistic regression models were used to control for potential confounders. Subgroup analyses were conducted according to birth order (first or second twin) and gestational age at delivery (< 37 or ≥ 37 weeks of gestation). RESULTS: Among 3873 twin pregnancies, in which vaginal delivery was planned, that delivered at ≥ 32 weeks' gestation with the first twin in cephalic presentation, meeting the inclusion criteria of the Twin Birth Study, 729 (18.8%) were uncomplicated monochorionic twin pregnancies and 3144 (81.2%) were dichorionic twin pregnancies. The rate of composite intrapartum mortality and neonatal morbidity and mortality did not differ between uncomplicated monochorionic (27/1458 (1.9%)) and dichorionic (107/6288 (1.7%)) twin pregnancies when adjusting for conception by assisted reproductive technologies (adjusted relative risk, 1.07 (95% CI, 0.66-1.75)). No significant difference in the primary outcome was found between the groups on subgroup analyses according to birth order and gestational age at delivery. CONCLUSION: When vaginal delivery is planned, and delivery occurs at ≥ 32 weeks of gestation with the first twin in cephalic presentation, uncomplicated monochorionic twin pregnancy is not associated with a higher rate of composite intrapartum mortality and neonatal morbidity and mortality compared with dichorionic twin pregnancy. © 2020 International Society of Ultrasound in Obstetrics and Gynecology.
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Parto Obstétrico/estatística & dados numéricos , Complicações do Trabalho de Parto/epidemiologia , Resultado da Gravidez/epidemiologia , Gravidez de Gêmeos , Gêmeos/estatística & dados numéricos , Adulto , Córion , Parto Obstétrico/métodos , Feminino , França/epidemiologia , Humanos , Recém-Nascido , Apresentação no Trabalho de Parto , Mortalidade Perinatal , Gravidez , Estudos Prospectivos , VaginaRESUMO
OBJECTIVE: Because the effectiveness of antenatal care in reducing pregnancy complications is still discussed despite widespread recommendations of its use, we sought to assess the association between utilisation of recommended antenatal care and severe maternal (SMM) and perinatal morbidity (SPM). DESIGN: Prospective cohort study. SETTING: Four maternity units around Paris in 2010-2012. SAMPLE: 9117 women with singleton pregnancies. METHODS: Logistic regression models adjusted for maternal social, demographic and medical characteristics. MAIN OUTCOME MEASURES: Antenatal care utilisation was assessed by: (1) initiation of care after 14 weeks, (2) < 50% of recommended visits made, according to gestational age, (3) absence of the first, second or third trimester ultrasounds, (4) two modified Adequacy of Prenatal Care Utilisation indexes, combining these components. The two main outcomes were composite variables of SMM and SPM. RESULTS: According to the modified Adequacy of Prenatal Care Utilisation index, 34.6% of women had inadequate antenatal care utilisation; the incidence of severe maternal morbidity (SMM) was 2.9% and severe perinatal morbidity (SPM) 5.5%. A percentage of recommended visits below 50% (2.6% of women) was associated with SMM [adjusted odds ratio (OR) 2.40 (1.38-4.17)] and SPM [aOR 2.27 (1.43-3.59)]. Late initiation of care (17.0% of women) was not associated with SMM or SPM. Failure to undergo the recommended ultrasounds (16, 17 and 22% of women) was associated with SPM. Inadequate antenatal care utilisation according to the index was associated with SPM [aOR 1.37 (1.05-1.80)]. CONCLUSION: Inadequate antenatal care utilisation is associated with SMM and SPM, to degrees that vary with the component of care and the outcome considered. TWEETABLE ABSTRACT: Inadequate antenatal care utilisation is associated with severe maternal and perinatal morbidity.
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Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Complicações na Gravidez/epidemiologia , Cuidado Pré-Natal/estatística & dados numéricos , Adulto , Feminino , Humanos , Modelos Logísticos , Razão de Chances , Paris/epidemiologia , Gravidez , Estudos ProspectivosRESUMO
OBJECTIVE: By-the-book implementation of non-invasive prenatal test and clinical validation for trisomy 21. STUDY DESIGN: Publicly funded prospective study of 225 cases. Women at risk for trisomy 21 > 1/250 based on combined ultrasound and serum markers during first or second trimester were eligible following an informed consent. The technique was established from the available literature and performed on 10 mL of venous blood collected prior to chorionic villus sampling or amniocentesis. Investigators were blinded to the fetal karyotype. Results were expressed in Z-scores of the percentage of each chromosome. RESULTS: Among 976 eligible cases, 225 were processed: 8 were used for pretesting phase and 23 to build a reference set. One hundred thirty six euploid cases and 47 with trisomy 21 were then run randomly. Eleven cases yielded no result (4.8%). Z-scores were above 3 (7.58+/-2.41) for chromosome 21 in all 47 trisomies and in none of the euploid cases (0.11+/-1.0). Z-scores were within normal range for the other chromosomes in both groups. Using a cut-off of 3, sensitivity and specificity were of 100% 95% CI [94.1, 100] and 100% 95% CI [98, 100], respectively. CONCLUSION: Non-invasive prenatal test for trisomy 21 is a robust strategy that can be translated from seminal publications. Publicly funded studies should refine its indications and cost-effectiveness in prenatal screening and diagnosis. © 2015 John Wiley & Sons, Ltd.
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DNA/sangue , Síndrome de Down/sangue , Adulto , Amniocentese , Amostra da Vilosidade Coriônica , Estudos de Coortes , Síndrome de Down/diagnóstico , Feminino , Humanos , Cariotipagem , Gravidez , Primeiro Trimestre da Gravidez , Segundo Trimestre da Gravidez , Diagnóstico Pré-Natal , Estudos Prospectivos , Reação em Cadeia da Polimerase em Tempo Real , Medição de RiscoRESUMO
OBJECTIVE: To establish normal current values of various biochemical parameters during pregnancy in the northern area of Paris (France) in a subgroup from the PreCARE cohort and to study their changes according to the term of pregnancy, and to determine the influence of maternal precarity. DESIGN: The PreCAREbio cohort of pregnant women was defined in the PreCARE study, a multicenter cohort study. SETTING: Participants completed detailed questionnaires at enrolment and immediately postpartum. Data were collected prospectively. 26 biochemical parameters were longitudinally assessed. POPULATION: All women registered to deliver or who delivered at one of the four participating university hospitals in Paris between October 2010 and November 2011 were eligible for study inclusion (n=10,419). METHODS: We studied 26 biochemical markers during pregnancy and the influence of maternal social deprivation. MAIN OUTCOME MEASURES: Baseline values for 26 biochemical markers and their changes according to the term of pregnancy, and the influence of maternal social deprivation on these biochemical markers. RESULTS: 386 patients with 1733 blood samples recruited in one of the four centers in the PreCARE cohort were included. Baseline concentrations (median, 2.5th and 97.5th percentile) for each marker and did not differ at the different time points. Mean concentrations of each biochemical marker did not differ between socially deprived women and non-socially deprived women. CONCLUSIONS: We have established normal values for 26 biochemical parameters during pregnancy. We have also shown no difference in these values between socially deprived and non- socially deprived women.
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OBJECTIVES: To determine whether the prognostic value of fetal serum ß-2-microglobulin is altered and whether the occurrence of fetal urinary ascites prevents kidney damage in cases of fetal obstructive uropathy with urinary ascites. METHODS: This was a retrospective study of cases of fetal bilateral obstructive uropathy that occurred between 2006 and 2010, for which both fetal serum and ascites samples were sent to our laboratory for analysis. ß-2-microglobulin was assayed in both fetal serum and the corresponding ascites. Renal outcome was analyzed. Histological features of the kidney in cases of termination of pregnancy and renal function of liveborn infants were recorded. RESULTS: Fourteen cases with analysis of fetal serum and fetal ascites in a context of urinary obstruction were included. Renal outcome was unfavorable in eight cases (57%) and favorable in six (43%). When fetal serum ß-2-microglobulin was < 5 mg/L, renal outcome was favorable in all cases (4/4). When fetal serum ß-2-microglobulin was ≥ 5 mg/L, 8/10 cases (80%) had an unfavorable renal outcome (sensitivity, 100%; specificity, 66%). CONCLUSION: Fetal serum ß-2-microglobulin reliably predicts postnatal renal outcome in obstructive uropathy complicated by urinary ascites. Moreover, urine extravasation does not seem to protect fetal renal function.
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Ascite/embriologia , Doenças Fetais , Obstrução Uretral/embriologia , Microglobulina beta-2/sangue , Ascite/complicações , Ascite/metabolismo , Biomarcadores/sangue , Feminino , Idade Gestacional , Taxa de Filtração Glomerular/fisiologia , Humanos , Nefropatias/embriologia , Nefropatias/fisiopatologia , Gravidez , Resultado da Gravidez , Diagnóstico Pré-Natal/métodos , Prognóstico , Estudos Retrospectivos , Obstrução Uretral/complicaçõesRESUMO
Alzheimer's disease is a neurodegenerative disorder which contributes to millions of cases of dementia worldwide. The dominant theoretical models of Alzheimer's disease propose that the brain passively succumbs to disruptions in proteostasis, neuronal dysfunction, inflammatory and other processes, ultimately leading to neurodegeneration and dementia. However, an emerging body of evidence suggests that the adult brain is endowed with endogenous mechanisms of resilience which may enable individuals to remain cognitively intact for years despite underlying pathology. In this brief review, we discuss evidence from basic neuroscience and clinical research which demonstrates the existence of endogenous molecular signaling pathways that can promote resilience to neurodegeneration. The p75 neurotrophin receptor provides one such pathway of resilience due to its role as a fundamental signaling switch which determines neuronal survival or degeneration. We highlight a series of preclinical studies targeting the p75 neurotrophin receptor in mouse models which demonstrate resilience to amyloid. We briefly discuss the design and goals of a recent clinical trial of p75 neurotrophin receptor modulation in patients with mild to moderate Alzheimer's disease. Unique challenges for developing therapeutics and biomarkers which are optimized for targeting and detecting endogenous mechanisms of resilience are also discussed. Altogether, this review motivates further trial work of therapeutics modulating the p75 neurotrophin receptor and other deep biology targets.
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Doença de Alzheimer , Animais , Humanos , Camundongos , Doença de Alzheimer/tratamento farmacológico , Peptídeos beta-Amiloides/metabolismo , Encéfalo/metabolismo , Receptor de Fator de Crescimento Neural/metabolismoRESUMO
Background: Different ST-segment elevation myocardial infarction (STEMI) localizations go along with dissimilarities in the size of the affected myocardium, the causing coronary vessel occlusion, and the right ventricular participation. Therefore, this study aims to clarify if there is any difference in long-term survival between anterior- and non-anterior-wall STEMI. Methods: This study included 2,195 incident STEMI cases that occurred between 2009 and 2017, recorded by the population-based Augsburg Myocardial Infarction Registry, Germany. The study population comprised 1.570 men and 625 women aged 25-84 years at acute myocardial infarction. The patients were observed from the day of their first acute event with an average follow-up period of 4.3 years, (standard deviation: 3.0). Survival analyses and multivariable Cox regression analyses were performed to examine the association between infarction localizations and long-term all-cause mortality. Results: Of the 2,195 patients, 1,118 had an anterior (AWS)- and 1,077 a non-anterior-wall-STEMI (NAWS). No significant associations of the STEMI localization with long-term mortality were found. When comparing AWS with NAWS, a hazard ratio of 0.91 [95% confidence interval: 0.75-1.10] could be calculated after multivariable adjustment. In contrast to NAWS, AWS was associated with a greater <28 day mortality, less current or former smoking and higher creatine kinase-myocardial band levels (CK-MB) and went along with a higher frequency of impaired left ventricular ejection fraction (<30%). Conclusions: Despite pathophysiological differences between AWS and NAWS, and identified differences in multiple clinical characteristics, no significant differences in long-term mortality between both groups were observed.
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OBJECTIVE: To identify strategies for reducing neonatal and maternal morbidity associated with intrahepatic cholestasis pregnancy (ICP). MATERIAL AND METHODS: The quality of evidence of the literature was assessed following the GRADE methodology with questions formulated in the PICO format (Patients, Intervention, Comparison, Outcome) and outcomes defined a priori and classified according to their importance. An extensive bibliographic search was performed on PubMed, Cochrane, EMBASE and Google Scholar databases. The quality of the evidence was assessed (high, moderate, low, very low) and a (i) strong or (ii) weak recommendations or (iii) no recommendation were formulated. The recommendations were reviewed in two rounds with external reviewers (Delphi survey) to select the consensus recommendations. RESULTS: Of the 14 questions (from 12 PICO questions and one definition question outside the PICO format), there was agreement between the working group and the external reviewers on 14 (100%). The level of evidence of the literature was insufficient to provide a recommendation on two questions. ICP is defined by the occurrence of suggestive pruritus (palmoplantar, nocturnal) associated with a total bile acid level>10µmol/L or an alanine transaminase level above 2N after ruling out differential diagnoses. In the absence of suggestive symptoms of a differential diagnosis, it is recommended not to carry out additional biological or ultrasound tests. In women with CIP, ursodeoxycholic acid is recommended to reduce the intensity of maternal pruritus (Strong recommendation. Quality of the evidence moderate) and to decrease the level of total bile acids and alanine transaminases. (Strong recommendation. Quality of the evidence moderate). S-adenosyl-methionine, dexamethasone, guar gum or activated charcoal should not be used to reduce the intensity of maternal pruritus (Strong recommendation. Quality of evidence low), and there is insufficient data to recommend the use of antihistamines (No recommendation. Quality of evidence low). Rifampicin (Weak recommendation. Very low quality of evidence) or plasma exchange (Strong recommendation. Very low quality of evidence) should not be used to reduce maternal pruritus and perinatal morbidity. Serum monitoring of bile acids is recommended to reduce perinatal morbidity and mortality (stillbirth, prematurity) (Low recommendation. Quality of the evidence low). The level of evidence is insufficient to determine whether fetal heart rate or fetal ultrasound monitoring are useful to reduce perinatal morbidity (No recommendation). Birth is recommended when bile acid level is above 99µmol/L from 36 weeks gestation to reduce perinatal morbidity, in particular stillbirth. When bile acid level is above 99µmol/L is below 100µmol/L, women should be informed that induction of labor could be considered 37 and 39 weeks gestation to reduce perinatal morbidity. (Strong recommendation. Quality of evidence low). In postpartum, total bile acids and alanine transaminases level should be checked and normalized before prescribing estrogen-progestin contraception, ideally with a low estrogen dose (risk of recurrence of pruritus and cytolysis) (Low recommendation. Quality of evidence very low). CONCLUSION: Although the quality of evidence regarding ICP gestational cholestasis remains low, there is a strong consensus in France, as shown by our Delphi study, on how to manage women with ICP. The reference first-line treatment is ursodeoxycholic acid.
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Colestase Intra-Hepática , Complicações na Gravidez , Gravidez , Recém-Nascido , Feminino , Humanos , Natimorto/epidemiologia , Ácido Ursodesoxicólico/uso terapêutico , Obstetra , Ginecologista , Complicações na Gravidez/terapia , Complicações na Gravidez/tratamento farmacológico , Colestase Intra-Hepática/diagnóstico , Colestase Intra-Hepática/terapia , Colestase Intra-Hepática/complicações , Ácidos e Sais Biliares , Estrogênios/uso terapêutico , Prurido/diagnóstico , Prurido/etiologia , Prurido/terapia , Transaminases/uso terapêutico , Alanina/uso terapêuticoRESUMO
OBJECTIVE: To identify procedures to reduce maternal morbidity during cesarean. MATERIAL AND METHODS: The quality of evidence of the literature was assessed following the GRADE® method with questions formulated in the PICO format (Patients, Intervention, Comparison, Outcome) and outcomes defined a priori and classified according to their importance. An extensive bibliographic search was performed on PubMed, Cochrane and EMBASE databases. The quality of the evidence was assessed (high, moderate, low, very low) and a (i) strong or (ii) weak recommendations or (iii) no recommendation were formulated. The recommendations were reviewed in two rounds with external reviewers (Delphi survey) to select the consensus recommendations. RESULTS: Of the 27 questions, there was agreement between the working group and the external reviewers on 26. The level of evidence of the literature was insufficient to provide a recommendation on 15 questions. Preventing hypothermia is recommended to increase maternal satisfaction and comfort (weak recommendation) and to reduce neonatal hypothermia (strong recommendation). The quality of the evidence of the literature did not allow to recommend the skin disinfectant to be used nor the relevance of a preoperative vaginal disinfection nor the choice between the use or nonuse of an indwelling bladder catheterization (if micturition takes place 1 hour before the cesarean section). The Misgav-Ladach technique or its analogues should be considered rather than the Pfannenstiel technique to reduce maternal morbidity (weak recommendation) bladder flap before uterine incision should not be performed routinely (weak recommendation), but a blunt (weak recommendation) and cephalad-caudad extension of uterine incision (weak recommendation) should be considered to reduce maternal morbidity. Antibiotic prophylaxis is recommended to reduce maternal infectious morbidity (strong recommendation) without recommendation on its type or the timing of administration (before incision or after cord clamping). The administration of carbetocin after cord clamping does not significantly decrease the incidence of blood loss>1000 ml, anemia, or blood transfusion compared with the administration of oxytocin. Thus, it is not recommended to use carbetocin rather than oxytocin in cesarean. It is recommended that systematic manual removal of the placenta not to be performed (weak recommendation). An antiemetic should be administered after cord clamping in women having a planned cesarean under locoregional anaesthesia to reduce intraoperative and postoperative nausea and vomiting (strong recommendation) with no recommendation regarding choice of use one or two antiemetics. The level of evidence of the literature was insufficient to provide any recommendation concerning single or double-layer closure of the uterine incision, or the uterine exteriorization. Closing the peritoneum (visceral or parietal) should not be considered (weak recommendation). The quality of the evidence of the literature was not sufficient to provide recommendation on systematic subcutaneous closure, including in obese or overweight patients, or the use of subcuticular suture in obese or overweight patients. The use of subcuticular suture in comparison with skin closure by staples was not considered as a recommendation due to the absence of a consensus in the external review rounds. CONCLUSION: In case of cesarean, preventing hypothermia, administering antiemetic and antibiotic prophylaxis after cord clamping are the only strong recommendations. The Misgav-Ladach technique, the way of performing uterine incision (no systematic bladder flap, blunt cephalad-caudad extension), not performing routine manual removal of the placenta nor closure of the peritoneum are weak recommendations and may reduce maternal morbidity.
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Cesárea , Obstetrícia , Feminino , Humanos , Recém-Nascido , Gravidez , Antieméticos , Cesárea/efeitos adversos , Cesárea/métodos , Cesárea/normas , Ginecologista , Hipotermia/etiologia , Hipotermia/prevenção & controle , Obesidade , Obstetra , Sobrepeso , Ocitocina , França , Obstetrícia/normasRESUMO
OBJECTIVE: To assess perinatal outcomes after expectant management in the case of preterm prelabour rupture of membranes (PPROM) before 25 weeks of gestation, according to the rate of termination of pregnancy (TOP). DESIGN: Retrospective comparative cohort study. POPULATION: Singleton pregnancies complicated by PPROM between 15(0/7) and 24(6/7) weeks of gestation, from January 2003 to January 2007. METHODS: Comparison of perinatal outcomes in two French tertiary care referral centres presumed to have different rates of TOP. MAIN OUTCOME MEASURE: Rates of TOP, survival and survival without major morbidity. RESULTS: A total of 113 women experienced PPROM (49 in centre A and 64 in centre B). A lower proportion of patients opted for TOP in centre A (40.8%) than in centre B (56.3%). The baseline characteristics of patients and pregnancies, and gestational age at PPROM, were not different between the two centres. Mean gestational age at delivery (28.1 versus 25.4 weeks of gestation; P < 0.01), mean latency period (45.5 versus 16.1 days; P < 0.01), mean birthweight (1295 versus 929 g; P = 0.04) and survival (46.9 versus 20.3%; P < 0.01) were significantly higher in centre A than in centre B. The percentage of neonates alive without major morbidity was also higher in centre A than in centre B (42.9 versus 20.3%; P = 0.01). CONCLUSIONS: Perinatal outcomes of pregnancies managed expectantly were not better in the centre where the TOP rate was higher. The perinatal risk of pregnancies complicated by pre-viable PPROM remains high.
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Aborto Induzido/estatística & dados numéricos , Ruptura Prematura de Membranas Fetais/epidemiologia , Mortalidade Fetal , Mortalidade Perinatal , Adulto , Algoritmos , Estudos de Coortes , Parto Obstétrico/estatística & dados numéricos , Feminino , Ruptura Prematura de Membranas Fetais/etiologia , Ruptura Prematura de Membranas Fetais/mortalidade , França/epidemiologia , Idade Gestacional , Maternidades , Hospitais Universitários , Humanos , Recém-Nascido , Recém-Nascido Prematuro , Doenças do Prematuro/epidemiologia , Gravidez , Complicações na Gravidez/epidemiologia , Resultado da Gravidez , Estudos Retrospectivos , Taxa de Sobrevida , Fatores de TempoRESUMO
Boron determination in blood and tissue samples is a crucial task especially for treatment planning, preclinical research, and clinical application of boron neutron capture therapy (BNCT). Comparison of clinical findings remains difficult due to a variety of analytical methods, protocols, and standard reference materials in use. This paper addresses the comparability of inductively coupled plasma mass spectrometry, quantitative neutron capture radiography, and prompt gamma activation analysis for the determination of boron in biological samples. It was possible to demonstrate that three different methods relying on three different principles of sample preparation and boron detection can be validated against each other and yield consistent results for both blood and tissue samples. The samples were obtained during a clinical study for the application of BNCT for liver malignancies and therefore represent a realistic situation for boron analysis.
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Análise por Ativação/métodos , Boro/sangue , Espectrometria de Massas/métodos , Radiografia/métodos , Raios gama , HumanosRESUMO
AIMS: Prior studies demonstrated an association between hospital admission blood glucose and mortality in acute myocardial infarction (AMI). Because stress hyperglycemia ratio (SHR) has been suggested as a more reliable marker of stress hyperglycemia this study investigated to what extent SHR in comparison with admission blood glucose is associated with short- and long-term mortality in diabetic and non-diabetic AMI patients. METHODS: The analysis was based on 2,311 AMI patients aged 25-84 years from the population-based Myocardial Infarction Registry Augsburg (median follow-up time 6.5 years [IQR: 4.9-8.1]). The SHR was calculated as admission glucose (mg/dl)/(28.7 × HbA1c (%)-46.7). Using logistic and COX regression analyses the associations between SHR and admission glucose and mortality were investigated. RESULT: Higher admission glucose and higher SHR were significantly and nonlinearly associated with higher 28-day mortality in AMI patients with and without diabetes. In patients without diabetes, the AUC for SHR was significantly lower than for admission glucose (SHR: 0.6912 [95%CI 0.6317-0.7496], admission glucose: 0.716 [95%CI 0.6572-0.7736], p-value: 0.0351). In patients with diabetes the AUCs were similar for SHR and admission glucose. Increasing admission glucose and SHR were significantly nonlinearly associated with higher 5-year all-cause mortality in AMI patients with diabetes but not in non-diabetic patients. AUC values indicated a comparable prediction of 5-year mortality for both measures in diabetic and non-diabetic patients. CONCLUSIONS: Stress hyperglycemia in AMI patients plays a significant role mainly with regard to short-term prognosis, but barely so for long-term prognosis, underlining the assumption that it is a transient dynamic disorder that occurs to varying degrees during the acute event, thereby affecting prognosis.
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Diabetes Mellitus , Hiperglicemia , Infarto do Miocárdio , Glicemia , Humanos , PrognósticoRESUMO
OBJECTIVES: To evaluate the revision of methodology of the clinical practice guidelines (CPG) of the French National College of Gynecologists and Obstetricians (CNGOF). METHOD: Three CPGs were organized in 2020 on the topics of severe preeclampsia, menorrhagia, and prophylactic surgery according to AGREE II (Apraisal of Guidelines for Research & Evaluation). Questions were presented in PICO (Population, Intervention, Comparison, Outcome) format and the grading of scientific evidence was based on the GRADE (Grading of Recommendation Assessment, Development and Evaluation) method. RESULTS: All three CPGs groups adhered to this new methodology. However, the presentation of the arguments, the formulation of the recommendations and the development of the GRADE tables were heterogeneous from one group to another. A homogenization of the presentation is proposed, as well as a guide to the critical analysis of the literature to help the experts to rate the evidence. CONCLUSION: Adherence to these quality criteria should make it easier to apply the recommendations at the national level and improve international recognition of the work done by the CNGOF.
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Ginecologia , Pré-Eclâmpsia , Feminino , Humanos , Gravidez , Ginecologia/métodos , Guias de Prática Clínica como AssuntoRESUMO
OBJECTIVE: To determine the management of patients with 1st trimester nausea and vomiting and hyperemesis gravidarum. METHODS: A panel of experts participated in a formal consensus process, including focus groups and two Delphi rounds. RESULTS: Hyperemesis gravidarum is distinguished from nausea and vomiting during pregnancy by weight loss≥5 % or signs of dehydration or a PUQE score≥7. Hospitalization is proposed when there is, at least, one of the following criteria: weight loss≥10%, one or more clinical signs of dehydration, PUQE (Pregnancy Unique Quantification of Emesis and nausea) score≥13, hypokalemia<3.0mmol/L, hyponatremia<120mmol/L, elevated serum creatinine>100µmol/L or resistance to treatment. Prenatal vitamins and iron supplementation should be stopped without stopping folic acid supplementation. Diet and lifestyle should be adjusted according to symptoms. Aromatherapy is not to be used. If the PUQE score is<6, even in the absence of proof of their benefit, ginger, pyridoxine (B6 vitamin), acupuncture or electrostimulation can be used, even in the absence of proof of benefit. It is proposed that drugs or combinations of drugs associated with the least severe and least frequent side effects should always be chosen for uses in 1st, 2nd or 3rd intention, taking into account the absence of superiority of a class over another to reduce the symptoms of nausea and vomiting of pregnancy and hypermesis gravidarum. To prevent Gayet Wernicke encephalopathy, Vitamin B1 must systematically be administered for hyperemesis gravidarum needing parenteral rehydration. Patients hospitalized for hyperemesis gravidarum should not be placed in isolation (put in the dark, confiscation of the mobile phone or ban on visits, etc.). Psychological support should be offered to all patients with hyperemesis gravidarum as well as information on patient' associations involved in supporting these women and their families. When returning home after hospitalization, care will be organized around a referring doctor. CONCLUSION: This work should contribute to improving the care of women with hyperemesis gravidarum. However, given the paucity in number and quality of the literature, researchers must invest in the field of nausea and vomiting in pregnancy, and HG to identify strategies to improve the quality of life of women with nausea and vomiting in pregnancy or hyperemesis gravidarum.
Assuntos
Hiperêmese Gravídica , Feminino , Humanos , Gravidez , Consenso , Desidratação , Ginecologista , Hiperêmese Gravídica/terapia , Hiperêmese Gravídica/diagnóstico , Náusea/etiologia , Náusea/terapia , Obstetra , Qualidade de Vida , Redução de PesoRESUMO
OBJECTIVE: To provide national guidelines for the management of women with severe preeclampsia. DESIGN: A consensus committee of 26 experts was formed. A formal conflict of interest (COI) policy was developed at the onset of the process and enforced throughout. The entire guidelines process was conducted independently of any industrial funding. The authors were advised to follow the principles of the Grading of Recommendations Assessment, Development and Evaluation (GRADE®) system to guide assessment of quality of evidence. The potential drawbacks of making strong recommendations in the presence of low-quality evidence were emphasized. METHODS: The last SFAR and CNGOF guidelines on the management of women with severe preeclampsia was published in 2009. The literature is now sufficient for an update. The aim of this expert panel guidelines is to evaluate the impact of different aspects of the management of women with severe preeclampsia on maternal and neonatal morbidities separately. The experts studied questions within 7 domains. Each question was formulated according to the PICO (Patients Intervention Comparison Outcome) model and the evidence profiles were produced. An extensive literature review and recommendations were carried out and analyzed according to the GRADE® methodology. RESULTS: The SFAR/CNGOF experts panel provided 25 recommendations: 8 have a high level of evidence (GRADE 1±), 9 have a moderate level of evidence (GRADE 2±), and for 7 recommendations, the GRADE method could not be applied, resulting in expert opinions. No recommendation was provided for 3 questions. After one scoring round, strong agreement was reached between the experts for all the recommendations. CONCLUSIONS: There was strong agreement among experts who made 25 recommendations to improve practices for the management of women with severe preeclampsia.
Assuntos
Anestesiologia , Médicos , Pré-Eclâmpsia , Consenso , Cuidados Críticos , Feminino , Humanos , Recém-Nascido , Pré-Eclâmpsia/terapia , GravidezRESUMO
OBJECTIVES: To revise the organization and the methodology of the Practice Clinical Guidelines (PCG) of the French College of Gynecologists and Obstetricians (CNGOF). METHODS: The different available methods of PCG organization and of scientific evidence grading have been consulted after searching in the Medline database. RESULTS: The PCG group of the CNGOF has decided to adopt the AGREE II (for Appraisal of Guidelines for REsearch and Evaluation) methology for PCG organization and the GRADE (for Grading of Recommendation Assessment, Development, and Evaluation) system for grading scientific evidence. CONCLUSION: By adopting the AGREE II consortium criteria and grading scientific evidence according to the GRADE system, the CNGOF will increase the quality of the overall process, will deliver more targeted and easy to assimilate recommendations, to facilitate professional decision making.
Assuntos
Estudos de Avaliação como Assunto , Ginecologia/métodos , Obstetrícia/métodos , Guias de Prática Clínica como Assunto , Qualidade da Assistência à Saúde/organização & administração , Medicina Baseada em Evidências , Feminino , França , Ginecologia/organização & administração , Humanos , MEDLINE , Obstetrícia/organização & administraçãoRESUMO
OBJECTIVE: To determine the management of patients with term prelabor rupture of membranes. METHODS: Synthesis of the literature from the PubMed and Cochrane databases and the recommendations of French and foreign societies and colleges. RESULTS: Term prelabor rupture of membranes is considered a physiological process up to 12hours of rupture (Professional consensus). In case of expectant management and with a low rate of antibiotic prophylaxis, home care compared to hospitalization could be associated with an increase in neonatal infections (LE3), especially in case of group B streptococcus colonization (LE3). Home care is therefore not recommended (Grade C). In the absence of spontaneous labor within 12hours of rupture, antibiotic prophylaxis could reduce the risk of maternal intrauterine infection but not of neonatal infection (LE3). Its use after 12hours of rupture in term prelabor rupture of the membranes is therefore recommended (Grade C). When antibiotic prophylaxis is indicated, intravenous beta-lactams are recommended (Grade C). Induction of labor with oxytocin (LE1), prostaglandin E2 (LE1) or misoprostol (LE1), is associated with shorter rupture of membranes to delivery intervals when compared to expectant management. Compared with expectant management, immediate induction of labor is not associated with lower rates of neonatal infection (LE1), even among women with a positive streptococcus B vaginal swab (LE2). Thus, expectant management can be offered without increasing the risk of neonatal infection (Grade B). Induction of labor is not associated with an increase or decrease in the cesarean delivery rate (LE2), whatever parity (LE2) or Bishop score at admission (LE3). Induction can thus be proposed without increasing the risk of cesarean delivery (Grade B). No induction method (oxytocin, dinoprostone, misoprostol or Foley® catheter) has demonstrated superiority over another, whether to reduce rate of intrauterine or neonatal infection, rate of cesarean delivery or to shorten rupture of membranes to delivery intervals regardless of Bishop's score and parity. CONCLUSION: Term prelabor rupture of membranes is a frequent event. A 12-hour delay without onset of spontaneous labor was chosen to differentiate a physiological condition from a potentially unsafe situation justifying an antibiotic prophylaxis. Expectant management or induction of labor can both be proposed, even in case of positive screening for streptococcus B, depending on the patient's wishes and maternity units' organization (Professional consensus).