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1.
Nat Neurosci ; 27(5): 812-821, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38684891

RESUMO

Over the past few decades, numerous environmental chemicals from solvents to pesticides have been suggested to be involved in the development and progression of neurodegenerative diseases. Most of the evidence has accumulated from occupational or cohort studies in humans or laboratory research in animal models, with a range of chemicals being implicated. What has been missing is a systematic approach analogous to genome-wide association studies, which have identified dozens of genes involved in Alzheimer's disease, Parkinson's disease and other neurodegenerative diseases. Fortunately, it is now possible to study hundreds to thousands of chemical features under the exposome framework. This Perspective explores how advances in mass spectrometry make it possible to generate exposomic data to complement genomic data and thereby better understand neurodegenerative diseases.


Assuntos
Expossoma , Doenças Neurodegenerativas , Humanos , Doenças Neurodegenerativas/induzido quimicamente , Doenças Neurodegenerativas/genética , Animais , Exposição Ambiental/efeitos adversos , Estudo de Associação Genômica Ampla , Espectrometria de Massas
2.
J Matern Fetal Neonatal Med ; 37(1): 2332794, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38538322

RESUMO

OBJECTIVES: There have been significant advances in the medical management of severe postpartum hemorrhage (sPPH) over recent decades, which is reflected in numerous published guidelines. To date, many of the currently available national and international guidelines recommend recombinant factor VIIa (rFVIIa) to be used only at a very late stage in the course of sPPH, as a "last resort", before or after hysterectomy. Based on new safety data, rFVIIa has recently been approved by the European Medicines Agency (EMA) and Swissmedic for use in sPPH, if uterotonics are insufficient to achieve hemostasis, which in fact is significantly earlier in the course of postpartum hemorrhage (PPH). We therefore aimed to develop expert consensus guidance as a step toward standardizing care with the use of rFVIIa for clinicians managing women experiencing life-threatening sPPH. METHODS: The consensus process consisted of one face-to-face meeting with a group of nine experts, including eight obstetrician-gynecologists and a hematologist highly experienced in sPPH care in tertiary care perinatal centers. The panel was representative of multidisciplinary expertise in the European obstetrics community and provided consensus opinion in answer to pre-defined questions around clinical practice with rFVIIa in the management of sPPH. Recommendations have been based on current national and international guidelines, extensive clinical experience, and consensus opinion, as well as the availability of efficacy and new safety data. RESULTS: The expert panel developed 17 consensus statements in response to the 13 pre-defined questions on the use of rFVIIa in the management of sPPH including: available efficacy and safety data and the need for interdisciplinary expertise between obstetricians, anesthesiologists, and hematologists in the management of sPPH. Based on novel data, the experts recommend: (1) earlier administration of rFVIIa in patients with sPPH who do not respond to uterotonic administration to optimize the efficacy of rFVIIa; (2) the importance of hematological parameter prerequisites prior to the administration of rFVIIa to maximize efficacy; and (3) continued evaluation or initiation of further invasive procedures according to standard practice. Furthermore, recommendations on the timing of rFVIIa treatment within the sPPH management algorithm are outlined in a range of specified clinical scenarios and settings, including vaginal delivery, cesarean section, and smaller birthing units before transfer to a tertiary care center. The panel agreed that according to available, and new data, as well as real-world experience, there is no evidence that the use of rFVIIa in patients with sPPH increases the risk of thromboembolism. The authors acknowledge that there is still limited clinical effectiveness data, as well as pharmacoeconomic data, on the use of rFVIIa in sPPH, and recommend further clinical trials and efficacy investigation. CONCLUSIONS: This expert panel provides consensus guidance based on recently available data, clinical experience, and expert opinion, augmented by the recent approval of rFVIIa for use in sPPH by the EMA. These consensus statements are intended to support clinical care for sPPH and may help to provide the impetus and a starting point for updates to existing clinical practice guidelines.


Assuntos
Hemorragia Pós-Parto , Humanos , Feminino , Gravidez , Hemorragia Pós-Parto/tratamento farmacológico , Cesárea , Fator VIIa/uso terapêutico , Período Pós-Parto , Proteínas Recombinantes
3.
Int J Obstet Anesth ; 55: 103896, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37270857

RESUMO

Competency-based training and active teaching methods are increasingly becoming accepted and utilized in medical schools and hospitals, and obstetric anesthesiology training is expected to follow this process. This article summarizes current modalities of obstetric anesthesiology training in five countries from various parts of the world. Analysis of these curricula shows that implementation of new educational methods is variable, incomplete, and lacking in data related to patient outcomes. Research in assessments and practical applications are required to avoid wide ranges of educational strategies.


Assuntos
Anestesiologia , Internato e Residência , Humanos , Anestesiologia/educação , Currículo , Hospitais , Competência Clínica
4.
Hum Reprod ; 38(4): 701-715, 2023 04 03.
Artigo em Inglês | MEDLINE | ID: mdl-36881900

RESUMO

STUDY QUESTION: Are persistent organic pollutants (POPs) associated with a diminished ovarian reserve (DOR) in women of reproductive age? SUMMARY ANSWER: Amongst 17 POPs detected in over 20% of serum samples, only p,p'-DDE was significantly associated with an increased risk of DOR, and ß-hexachlorocyclohexane (ß-HCH) was significantly associated with a decreased risk of DOR whilst mixture analyses yielded non-significant associations and did not detect any interactions between POPs. WHAT IS KNOWN ALREADY: Animal studies have shown that several POPs can alter folliculogenesis and increase follicle depletion. However, only a few studies have been conducted in humans, with small sample sizes and inconsistent results. STUDY DESIGN, SIZE, DURATION: Our study included 138 cases and 151 controls from the AROPE case-control study. Study participants were women between 18 and 40 years of age recruited amongst couples consulting for infertility in four fertility centres in western France between 2016 and 2020. PARTICIPANTS/MATERIALS, SETTING, METHODS: Cases of DOR were defined as women with anti-Müllerian hormone (AMH) levels ≤1.1 ng/ml and/or antral follicle count (AFC) <7, and controls were women with AMH levels between 1.1 and 5 ng/ml and AFC ≥ 7, without genital malformations and with a menstrual cycle length between 26 and 35 days. A total of 43 POPs (including 15 organochlorine pesticides, 17 polychlorinated biphenyls, and 9 polybromodiphenylethers) were measured in the serum at inclusion into the study. We conducted logistic regression adjusted for potential confounders using a directed acyclic graph to study the effect of each POP on DOR as single exposures, and used Bayesian kernel machine regression (BKMR) to measure the mixture effect of POPs on DOR. MAIN RESULTS AND THE ROLE OF CHANCE: Of the 43 POPs, 17 were detected in over 20% of the serum samples. In the single-exposure multivariate logistic regressions, p,p'-DDE (median 165.0 IQR 161.0 ng/l in controls) as a continuous exposure was significantly associated with an increased risk of DOR (odds ratio (OR) 1.39, 95% CI 1.10-1.77) and non-significantly associated with an increased risk of DOR for the second and third terciles (OR 1.46, 95% CI 0.74-2.87, and OR 1.72, 95% CI 0.88-3.37, respectively). ß-HCH (median 24.2 IQR 21.5 ng/l in controls) was significantly associated with a decreased risk of DOR when ß-HCH was treated as a continuous exposure (OR 0.63, 95% CI 0.44-0.89) and for the third tercile of exposure (OR 0.43, 95% CI 0.21-0.84) and non-significantly associated with a decreased risk of DOR for the second tercile (OR 0.77, 95% CI 0.42-1.42). All sensitivity analyses confirmed our results. BKMR showed similar associations for single exposures but found no significant associations for the total mixture effect. In addition, the BKMR results did not suggest any interactions between POPs. LIMITATIONS, REASONS FOR CAUTION: Controls were recruited amongst infertile couples and thus may not be representative of all women of reproductive age. However, their POP concentrations were in the same range as in the general French population. WIDER IMPLICATIONS OF THE FINDINGS: This study is the first to examine the associations between serum POPs and DOR. The well-recognized anti-androgenic properties of p,p'-DDE and estrogenic properties of ß-HCH could explain these associations of opposite direction. If these results are replicated elsewhere, this could have an impact on fertility prevention messages and help in understanding the impact of POPs on the female reproductive system. STUDY FUNDING/COMPETING INTEREST(S): This study was funded by the Fondation de France (grant numbers 2014-50537 and 00110196) and the French Biomedicine Agency (2016). None of the authors have any conflicts of interest to declare. TRIAL REGISTRATION NUMBER: N/A.


Assuntos
Poluentes Ambientais , Infertilidade Feminina , Doenças Ovarianas , Reserva Ovariana , Feminino , Humanos , Masculino , Estudos de Casos e Controles , Poluentes Orgânicos Persistentes , Teorema de Bayes , Diclorodifenil Dicloroetileno , Poluentes Ambientais/efeitos adversos , Hormônio Antimülleriano
6.
Artigo em Inglês | BIGG - guias GRADE | ID: biblio-1415025

RESUMO

To provide recommendations on the management of urgent obstetrical emergencies outside the maternity ward. A group of 24 experts from the French Society of Emergency Medicine (SFMU), the French Society of Anaesthesia and Intensive Care Medicine (SFAR) and the French College of Gynaecologists and Obstetricians (CNGOF) was convened. Potential conflicts of interest were formally declared at the outset of the guideline development process, which was conducted independently of industry funding. The authors followed the GRADE (Grading of Recommendations Assessment, Development and Evaluation) method to assess the level of evidence in the literature. The potential drawbacks of strong recommendations in the presence of low-level evidence were highlighted. Some recommendations with an insufficient level of evidence were not graded. Eight areas were defined: imminent delivery, postpartum haemorrhage (prevention and management), threat of premature delivery, hypertensive disorders in pregnancy, trauma, imaging, cardiopulmonary arrest, and emergency obstetric training. For each field, the expert panel formulated questions according to the PICO model (population, intervention, comparison, outcomes) and an extensive literature search was conducted. Analysis of the literature and formulation of recommendations were conducted according to the GRADE method. Fifteen recommendations on the management of obstetrical emergencies were issued by the SFMU/SFAR/CNGOF panel of experts, and 4 recommendations from formalised expert recommendations (RFE) established by the same societies were taken up to answer 4 PICO questions dealing with the pre-hospital context. After two rounds of voting and several amendments, strong agreement was reached for all the recommendations. For two questions (cardiopulmonary arrest and inter-hospital transfer), no recommendation could be made. There was significant agreement among the experts on strong recommendations to improve practice in the management of urgent obstetric complications in emergency medicine.


Assuntos
Humanos , Feminino , Gravidez , Complicações na Gravidez/prevenção & controle , Administração dos Cuidados ao Paciente , Medicina de Emergência/normas
7.
Environ Int ; 168: 107435, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35994798

RESUMO

The use of organophosphate flame retardants (OPFRs) has been on the rise ever since many brominated flame retardants were banned, back in the 2000 s. The objectives of this study are to describe the pre- and post-natal exposure of children to OPFRs, and to explore their possible determinants. A total of 259 children aged 3.5 years and 388 mothers from the French ELFE mother-child cohort were included. Both pre- and post-natal exposure to OPFRs were assessed, using OPFR concentrations in the hair of pregnant women (in 2011) and their 3.5-year-old children (in 2014-2015) for 15 OPFRs, of which 9 were detected in > 20 % hair samples. The highest geometric means for pre-natal exposure were 272 ng/g for tris(1-chloro-2-propyl) phosphate (TCPP), 69.7 ng/g for ng/g for triphenyl phosphate (TPP) and 54.4 ng/g for tris(1,3-dichloro-2-propyl) phosphate (TDCPP). The highest geometric means for post-natal exposure were 249.6 ng/g for TCPP, 85.3 ng/g for TDCPP and 83.8 ng/g for 2-ethylhexyl diphenyl phosphate (EHDPP). Correlations were found between both pre-natal exposures, and between pre-and post-natal exposures. No correlation was however found between pre-and post-natal exposures for any given OPFR. Pre-natal exposure to the 9 OPFRs was associated with pre-natal exposure to polybrominated diphenyl ethers 209 (BDE209), and 47 (BDE47). Maternal BMI was associated with pre-natal exposure to OPFRs other than TBEP. Home renovation work prior to birth was also associated with pre-natal exposure to OPFRs, with the exception of EHDPP, tris(2-butoxyethyl) phosphate (TBEP) and triethyl phosphate (TEP). Determinants of post-natal exposure appeared more disparate across OPFRs; although both the type of flooring in children's rooms and pre-natal exposure to polybrominated diphenyl ethers seem to be associated with post-natal exposure. Lastly, higher socioeconomic status appeared to be associated with lower exposure for several (though not all) OPFRs. The high prevalence of exposure to OPFRs suggests the need for studies to assess the health effects of OPFRs exposure, particularly on children.

8.
ESMO Open ; 7(1): 100346, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34954496

RESUMO

BACKGROUND: Tumor dynamics typically rely on the sum of the longest diameters (SLD) of target lesions, and ignore heterogeneity in individual lesion dynamics located in different organs. PATIENTS AND METHODS: Here we evaluated the benefit of analyzing lesion dynamics in different organs to predict survival in 900 patients with metastatic urothelial carcinoma treated with atezolizumab or chemotherapy (IMvigor211 trial). RESULTS: Lesion dynamics varied largely across organs, with lymph nodes and lung lesions showing on average a better response to both treatments than those located in the liver and locoregionally. A benefit of atezolizumab was observed on lung and liver lesion dynamics that was attributed to a longer duration of treatment effect as compared to chemotherapy (P value = 0.043 and 0.001, respectively). The impact of lesion dynamics on survival, assessed by a joint model, varied greatly across organs, irrespective of treatment. Liver and locoregional lesion dynamics had a large impact on survival, with an increase of 10 mm of the lesion size increasing the instantaneous risk of death by 12% and 10%, respectively. In comparison, lymph nodes and lung lesions had a lower impact, with a 10-mm increase in the lesion size increasing the instantaneous risk of death by 7% and 5%, respectively. Using our model, we could anticipate the benefit of atezolizumab over chemotherapy as early as 6 months before the end of the study, which is 3 months earlier than a similar model only relying on SLD. CONCLUSION: We showed the interest of organ-level tumor follow-up to better understand and anticipate the treatment effect on survival.


Assuntos
Carcinoma de Células de Transição , Neoplasias da Bexiga Urinária , Anticorpos Monoclonais Humanizados/farmacologia , Anticorpos Monoclonais Humanizados/uso terapêutico , Carcinoma de Células de Transição/tratamento farmacológico , Humanos , Recidiva Local de Neoplasia/induzido quimicamente , Recidiva Local de Neoplasia/tratamento farmacológico
9.
Br J Surg ; 108(10): 1225-1235, 2021 10 23.
Artigo em Inglês | MEDLINE | ID: mdl-34498666

RESUMO

BACKGROUND: The incidence of gastric poorly cohesive carcinoma (PCC) is increasing. The prognosis for patients with peritoneal metastases remains poor and the role of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is controversial. The aim was to clarify the impact of gastric PCC with peritoneal metastases treated by CRS with or without HIPEC. METHODS: All patients with peritoneal metastases from gastric cancer treated with CRS with or without HIPEC, in 19 French centres, between 1989 and 2014, were identified from institutional databases. Clinicopathological characteristics and outcomes were compared between PCC and non-PCC subtypes, and the possible benefit of HIPEC was assessed. RESULTS: In total, 277 patients were included (188 PCC, 89 non-PCC). HIPEC was performed in 180 of 277 patients (65 per cent), including 124 of 188 with PCC (66 per cent). Median overall survival (OS) was 14.7 (95 per cent c.i. 12.7 to 17.3) months in the PCC group versus 21.2 (14.7 to 36.4) months in the non-PCC group (P < 0.001). In multivariable analyses, PCC (hazard ratio (HR) 1.51, 95 per cent c.i. 1.01 to 2.25; P = 0.044) was associated with poorer OS, as were pN3, Peritoneal Cancer Index (PCI), and resection with a completeness of cytoreduction score of 1, whereas HIPEC was associated with improved OS (HR 0.52; P < 0.001). The benefit of CRS-HIPEC over CRS alone was consistent, irrespective of histology, with a median OS of 16.7 versus 11.3 months (HR 0.60, 0.39 to 0.92; P = 0.018) in the PCC group, and 34.5 versus 14.3 months (HR 0.43, 0.25 to 0.75; P = 0.003) in the non-PCC group. Non-PCC and HIPEC were independently associated with improved recurrence-free survival and fewer peritoneal recurrences. In patients who underwent HIPEC, PCI values of below 7 and less than 13 were predictive of OS in PCC and non-PCC populations respectively. CONCLUSION: In selected patients, CRS-HIPEC offers acceptable outcomes among those with gastric PCC and long survival for patients without PCC.


Assuntos
Procedimentos Cirúrgicos de Citorredução , Quimioterapia Intraperitoneal Hipertérmica , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Intervalo Livre de Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Neoplasias Ovarianas/secundário , Neoplasias Peritoneais/secundário , Prognóstico , Estudos Retrospectivos , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia , Adulto Jovem
10.
Phys Rev Lett ; 127(1): 012501, 2021 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-34270302

RESUMO

A microscopic calculation of half-lives for both the α and 2α decays of ^{212}Po and ^{224}Ra is performed, using a self-consistent framework based on energy density functionals. A relativistic density functional and a separable pairing interaction of finite range are used to compute axially symmetric deformation energy surfaces as functions of quadrupole, octupole, and hexadecapole collective coordinates. Dynamical least-action paths are determined, that trace the α and 2α emission from the equilibrium deformation to the point of scission. The calculated half-lives for the α decay of ^{212}Po and ^{224}Ra are in good agreement with data. A new decay mode, the symmetric 2α emission, is predicted with half-lives of the order of those observed for cluster emission.

11.
BJOG ; 128(11): 1814-1823, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-33713384

RESUMO

OBJECTIVE: To assess the benefits and safety of early human fibrinogen concentrate in postpartum haemorrhage (PPH) management. DESIGN: Multicentre, double-blind, randomised placebo-controlled trial. SETTING: 30 French hospitals. POPULATION: Patients with persistent PPH after vaginal delivery requiring a switch from oxytocin to prostaglandins. METHODS: Within 30 minutes after introduction of prostaglandins, patients received either 3 g fibrinogen concentrate or placebo. MAIN OUTCOME MEASURES: Failure as composite primary efficacy endpoint: at least 4 g/dl of haemoglobin decrease and/or transfusion of at least two units of packed red blood cells within 48 hours following investigational medicinal product administration. Secondary endpoints: PPH evolution, need for haemostatic procedures and maternal morbidity-mortality within 6 ± 2 weeks after delivery. RESULTS: 437 patients were included: 224 received FC and 213 placebo. At inclusion, blood loss (877 ± 346 ml) and plasma fibrinogen (4.1 ± 0.9 g/l) were similar in both groups (mean ± SD). Failure rates were 40.0% and 42.4% in the fibrinogen and placebo groups, respectively (odds ratio [OR] = 0.99) after adjustment for centre and baseline plasma fibrinogen; (95% CI 0.66-1.47; P = 0.96). No significant differences in secondary efficacy outcomes were observed. The mean plasma FG was unchanged in the Fibrinogen group and decreased by 0.56 g/l in the placebo group. No thromboembolic or other relevant adverse effects were reported in the Fibrinogen group versus two in the placebo group. CONCLUSIONS: As previous placebo-controlled studies findings, early and systematic administration of 3 g fibrinogen concentrate did not reduce blood loss, transfusion needs or postpartum anaemia, but did prevent plasma fibrinogen decrease without any subsequent thromboembolic events. TWEETABLE ABSTRACT: Early systematic blind 3 g fibrinogen infusion in PPH did not reduce anaemia or transfusion rate, reduced hypofibrinogenaemia and was safe.


Assuntos
Parto Obstétrico/efeitos adversos , Fibrinogênio/administração & dosagem , Hemostáticos/administração & dosagem , Hemorragia Pós-Parto/tratamento farmacológico , Adulto , Transfusão de Sangue/estatística & dados numéricos , Parto Obstétrico/métodos , Método Duplo-Cego , Feminino , Humanos , Ocitócicos/administração & dosagem , Ocitocina/administração & dosagem , Gravidez , Prostaglandinas/administração & dosagem , Prevenção Secundária , Resultado do Tratamento , Vagina
14.
Gynecol Obstet Fertil Senol ; 48(9): 646-648, 2020 09.
Artigo em Francês | MEDLINE | ID: mdl-32590078

RESUMO

Antibiotic prophylaxis is not recommended during surgical induced abortions. Systematic screening for Chlamydia trachomatis and Neisseria gonorrheae infection by polymerase chain reaction (PCR) on a vaginal sample is recommended before any surgical abortion. Moreover, the bacteriological result should be available before the abortion so that antibiotic treatment effective against the identified bacteria, if any, can be proposed before the procedure. The absence of bacteriological result on the day of the abortion must not, however, delay the procedure. If screening is positive for a sexually transmitted infection (STI), and the bacteriological result is only available after the abortion, it is recommended that antibiotic treatment start as soon as possible. The first-line antibiotic treatment is ceftriaxone 500mg in a single dose by the intramuscular route for N. gonorrheae, doxycycline 200mg per day orally for 7 days for C. trachomatis and azithromycin 500mg the first day (D1) then 250mg per day from D2 to D4 orally if Mycoplasma genitalium is detected by multiplex PCR. In case of positive screening, antibiotic treatment of the woman's partner(s) is recommended, adapted to the STI agent(s).


Assuntos
Aborto Induzido , Doença Inflamatória Pélvica , Antibioticoprofilaxia , Chlamydia trachomatis , Feminino , Humanos , Doença Inflamatória Pélvica/prevenção & controle , Gravidez , Primeiro Trimestre da Gravidez
15.
Anaesthesia ; 75(6): 800-808, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32012226

RESUMO

Phenylephrine is recommended for the management of hypotension after spinal anaesthesia in women undergoing caesarean section. Noradrenaline, an adrenergic agonist with weak ß-adrenergic activity, has been reported to have a more favourable haemodynamic profile than phenylephrine. However, there are concerns that noradrenaline may be associated with a higher risk of fetal acidosis, defined as an umbilical artery pH < 7.20. We performed a systematic review of trials comparing noradrenaline with phenylephrine, concentrating on primary outcomes of fetal acidosis and maternal hypotension. We identified 13 randomised controlled trials including 2002 patients. Heterogeneity among the studies was high, and there were too few data to calculate a pooled effect estimate. Fetal acidosis was assessed in four studies that had a low risk of bias and a low risk of confounding, that is, studies which used a prophylactic vasopressor and where women received the allocated vasopressor only. There were no significant differences between these studies. No significant differences were observed for hypotension. Two trials found a significantly lower incidence of bradycardia when using noradrenaline. Cardiac output was significantly higher after noradrenaline in two of three studies. For other secondary outcomes including nausea, vomiting and Apgar scores at 1 and 5 min, no studies found significant differences. The evidence so far is too limited to support an advantage of noradrenaline over phenylephrine. Concerns of a deleterious effect of noradrenaline on fetal blood gas status cannot currently be assuaged by the available data from randomised controlled studies.


Assuntos
Anestesia Obstétrica/efeitos adversos , Raquianestesia/efeitos adversos , Cesárea , Hipotensão/prevenção & controle , Norepinefrina/uso terapêutico , Fenilefrina/uso terapêutico , Adulto , Feminino , Humanos , Hipotensão/induzido quimicamente , Gravidez , Vasoconstritores/uso terapêutico
17.
BJS Open ; 3(2): 195-202, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30957067

RESUMO

Background: Pseudomyxoma peritonei (PMP) is a rare clinical condition characterized by mucinous ascites, typically related to appendiceal or ovarian tumours. Current standard treatment involves cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC), but recurrences occur in 20-30 per cent of patients. The aim of this study was to define the timing and patterns of recurrence to provide a basis for modifying follow-up of these patients. Methods: This observational study examined a prospectively developed multicentre national database (RENAPE working group) to identify patients with recurrence after optimal CRS and HIPEC for PMP. Postoperative complications, long-term outcomes and potential prognostic factors were evaluated. Results: Of 1411 patients with proven PMP, 948 were identified who had undergone curative CRS and HIPEC. Among these patients, 229 first recurrences (24·2 per cent) were identified: 196 (20·7 per cent) occurred within the first 5 years (early recurrence) and 30 (3·2 per cent) occurred between 5 and 10 years. Three patients developed a first recurrence more than 10 years after the original treatment. The mean(s.d.) time to first recurrence was 2·36(2·21) years. Preoperative chemotherapy and high-grade pathology were significant factors for early recurrence. Overall survival for the entire group was 77·9 and 63·1 per cent at 5 and 10 years respectively. The principal site of recurrence was the peritoneum. Conclusion: Recurrence of PMP was rare after 5 years and exceptional after 10 years.


Assuntos
Procedimentos Cirúrgicos de Citorredução/métodos , Hipertermia Induzida/métodos , Recidiva Local de Neoplasia/diagnóstico , Neoplasias Peritoneais/terapia , Pseudomixoma Peritoneal/terapia , Adulto , Idoso , Terapia Combinada/métodos , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/epidemiologia , Recidiva Local de Neoplasia/prevenção & controle , Neoplasias Peritoneais/mortalidade , Neoplasias Peritoneais/patologia , Peritônio/patologia , Peritônio/cirurgia , Prognóstico , Estudos Prospectivos , Pseudomixoma Peritoneal/mortalidade , Pseudomixoma Peritoneal/patologia , Estudos Retrospectivos , Fatores de Tempo
18.
J Mech Behav Biomed Mater ; 96: 144-151, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31035065

RESUMO

This study investigates the influence of a rapid heat treatment followed by water-quenching on the mechanical properties of Ti6Al4V ELI alloy to improve its strength for use in implants. Prior to the experiment, a dilatometry test was performed to understand the progressive α-to ß-phase transformation taking place during heating. The results were then used to carry out heat treatments. Microstructure was analysed using SEM, EBSD, EDX and XRD techniques. Vickers micro-hardness, tensile and high cycle rotating bending tests were used to analyse the influence of the $\alpha'$-phase fraction on the strength of the studied alloy. Results show that this process can provide a Ti6Al4V ELI alloy with a better Yield Strength (YS)/uniform deformation (εu) ratio and improved high cycle fatigue strength than those observed in the current microstructure used in medical implants. Lastly, cytotoxicity tests were performed on two types of human cells, namely MG63 osteoblast-like cells and fibroblasts. The results reveal the non-toxicity of the heat-treated Ti6Al4V ELI alloy.


Assuntos
Ligas/química , Temperatura Alta , Teste de Materiais , Fenômenos Mecânicos , Titânio/química , Titânio/toxicidade , Água/química , Linhagem Celular , Humanos , Osteoblastos/efeitos dos fármacos
20.
Orthop Traumatol Surg Res ; 105(3): 563-568, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30862491

RESUMO

INTRODUCTION: The development of outpatient surgery, cost-reduction pressures and instrumentation storage limitations have led to their use "just-in-time". A recent study showed that stoppage of surgical procedures immediately before the incision (No-Go) was often due to the management of supplies and implantable medical devices. To our knowledge, since the development of outpatient surgery and the shortening of hospital stays, managing the flow of instrumentation has not been optimized. At our hospital, we used a two-prong approach consisting of a tool to manage instrumentation and working group from the sterilization and orthopedic surgery units. The aims of this study were to: 1) evaluate whether this approach led to better notification of the risk of supply shortage for instrumentation and 2) determine whether it could reduce by at least half operating room disruptions such as delays or cancellation of surgical procedures. HYPOTHESIS: This approach results in better notification of the risk of supply shortage for instrumentation and reduces by at least half operating room disruptions such as delays or cancellation of surgical procedures. MATERIAL AND METHODS: A tool was developed to manage instrumentation flow based on a retrospective analysis of data from 2015. This tool consisted of: (1) a list of instrumentation needed for each surgical procedure from an analysis of the surgical schedule and verification of traceability labels of the instrumentation actually used, (2) a list of reasons for supply shortage identified from an analysis of non-conformities occurring in the sterilization process of instrumentation kits. These analyses resulted in the development of checklists for instrument sets for each procedure, while identifying those with a high risk of shortage. In 2017, a working group focused on instrumentation was set up with personnel from the sterilization unit and the orthopedic surgery unit. Based on the check-lists and the schedule 24hours before the surgery, the sterilization unit alerted the surgery unit by email of the risk of material shortage; the surgery ward replied with potential changes to the material or the surgery planning. This approach (instrumentation management tool and working group) was named just-in-time (JIT). The main outcome was the number of notifications of potential supply shortage with and without JIT over a 10-week period. The secondary outcomes were the number of notifications resolved in time and the occurrence of operating room disruptions (delay>30min or postponement of surgery) related to unavailable instrumentation. RESULTS: Nine reasons for potential supply shortage were identified such as instrumentation kits used for several types of procedures, those with fast rotation and low stock, or in double pathways (on loan and on deposit). The working group reported 163 potential shortages with JIT versus 41 without (p<10-5), of which 150 (92.5%) were resolved. Thirteen operating room disruptions occurred; only one was not detected by the JIT approach. CONCLUSION: Our JIT approach (instrumentation management tool and working group) is effective at preventing instrumentation supply shortages. LEVEL OF EVIDENCE: III, prospective comparative study.


Assuntos
Agendamento de Consultas , Procedimentos Ortopédicos/instrumentação , Ortopedia/organização & administração , Esterilização/organização & administração , Instrumentos Cirúrgicos/provisão & distribuição , Procedimentos Cirúrgicos Ambulatórios/instrumentação , Lista de Checagem , Humanos , Colaboração Intersetorial , Estudos Prospectivos , Estudos Retrospectivos
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