Serum persistent organic pollutants and diminished ovarian reserve: a single-exposure and mixture exposure approach from a French case-control study.

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.

Prognosis of poorly cohesive gastric cancer after complete cytoreductive surgery with or without hyperthermic intraperitoneal chemotherapy (CYTO-CHIP study).

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.

Microscopic Description of 2α Decay in

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.

Early and systematic administration of fibrinogen concentrate in postpartum haemorrhage following vaginal delivery: the FIDEL randomised controlled trial.

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.

A systematic review of phenylephrine vs. noradrenaline for the management of hypotension associated with neuraxial anaesthesia in women undergoing caesarean section.

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.

Semi-volatile organic compounds in the air and dust of 30 French schools: a pilot study.

The contamination of indoor environments with chemical compounds released by materials and furniture, such as semi-volatile organic compounds (SVOCs), is less documented in schools than in dwellings-yet children spend 16% of their time in schools, where they can also be exposed. This study is one of the first to describe the contamination of the air and dust of 90 classrooms from 30 nursery and primary schools by 55 SVOCs, including pesticides, phosphoric esters, musks, polycyclic aromatic hydrocarbons (PAHs), polychlorobiphenyls (PCBs), phthalates, and polybromodiphenylethers (PBDEs). Air samples were collected using an active sampling method, and dust samples were collected via two sampling methods (wiping and vacuum cleaning). In air, the highest concentrations (median >100 ng/m3 ) were measured for diisobutyl phthalate (DiBP), dibutyl phthalate (DBP), diethyl phthalate (DEP), bis(2-ethylhexyl) phthalate (DEHP), and galaxolide. In dust, the highest concentrations (median >30 µg/g) were found for DEHP, diisononyl phthalate (DiNP), DiBP, and DBP. An attempt to compare two floor dust sampling methods using a single unit (ng/m²) was carried out. SVOC concentrations were higher in wiped dust, but frequencies of quantification were greater in vacuumed dust.

[Follow-up of patients treated by VKA: Interest of a pharmaceutical link between the hospital and the retail pharmacies]. / Suivi des patients traités par AVK : intérêt d'un relais pharmaceutique entre l'hôpital et la ville.

Vitamin K antagonists (VKA) are used by 1,7% of the French population. Patient education and monitoring can decrease the number of iatrogenic hospitalizations due to VKA. We assessed the impact of a communication between hospital and retail pharmacists about patient's knowledge on VKA. The aim of our study has been to evaluate the value added by the link between the hospital pharmacist and the community pharmacist on the follow-up of patients treated by vitamin K antagonist. Patient information about VKA treatment is offered to inpatients in our hospital. An information form is filled for each patient treated by VKA. Patient's knowledge is assessed on the document (Name of VKA, cause of treatment, monitoring, risks of overdose, compliance…). This form is sent to the community pharmacist after the training when the patient leaves the hospital (by fax or by email). The form is sent back by the community pharmacist after the second training. Sixty-eight patients received the training, 48 forms have been sent to the retail pharmacists and 43 forms have been sent back to the hospital. Seven retail pharmacists replied spontaneously. Twenty-eight patients increased their knowledge (in average+21%) and 12 patients stabilized their knowledge. The best-known concepts were the INR target, the time of drug intake, the risks of overdose and the information of the family. The improvement of knowledge is significant for the name of VKA, the cause of treatment, efficacy assessment and signs of overdose. The implementation of a communication between the hospital and the retail pharmacies is time-consuming but the follow-up of those patients seems essential to keep a good knowledge.

Neutrophil-to-lymphocyte ratio as a prognostic biomarker for men with metastatic castration-resistant prostate cancer receiving first-line chemotherapy: data from two randomized phase III trials.

BACKGROUND: The neutrophil-to-lymphocyte ratio (NLR), a marker of host inflammation, has been associated with poor outcome in several solid tumors. Here, we investigated associations of the derived NLR (dNLR) and duration of initial androgen deprivation therapy (ADT) with survival of men with metastatic castration-resistant prostate cancer (mCRPC) receiving first-line chemotherapy. PATIENTS AND METHODS: Data from the multinational randomized phase III studies VENICE and TAX327 included a total of 2230 men with mCRPC randomized to receive first-line chemotherapy, and were used as training and validation sets, respectively. Associations of dNLR and duration of initial ADT with overall survival (OS) were evaluated by multivariable Cox regression analysis in the training set stratified for performance status and treatment arm. The model was then tested in the validation set. Subsequently, we investigated the treatment effect of docetaxel on OS in subgroups according to dNLR and duration of initial ADT. RESULTS: In the training set, both dNLR ≥median (2) and duration of initial ADT

[Security of the medicinal therapy: Cartography of risks a priori within service of orthopaedic surgery]. / Sécurisation de la prise en charge médicamenteuse : cartographie des risques a priori au sein du service de chirurgie orthopédique.

INTRODUCTION: Security and quality of the Medicinal Therapy are one of the most important objectives of the April 6th, 2011 order. The objective is to realize this study of the risks incurred by patients related to management and security of medicinal therapy in order to establish a plan to reduce the risks of drug's dispensation. MATERIALS AND METHOD: The method of the Preliminary Risk Analysis (PRA) has been implemented by a multidisciplinary group in a hospital service of orthopaedic surgery. The study focused on the dispensation phase of medicinal circuit. RESULTS: This analysis revealed 148 scenarii, 35 were criticality unacceptable. Fifty-four initial risk control actions were proposed and their stress levels to put them in place were evaluated. DISCUSSION: The main measures of risk management are: training, information, communication, computerization, automation, dual control, updating the documentation system, drug reconciliation and respect for Best Practices Hospitallers (BPH). CONCLUSIONS: Risk management requires a significant human and financial investment as well as, material resources and multidisciplinary expertise in order to offer the best solutions.

Temporal profile of lymphocyte counts and relationship with infections with fingolimod therapy.

BACKGROUND: Reduction in peripheral blood lymphocytes is an expected pharmacodynamic outcome of fingolimod therapy. OBJECTIVE: The objective of this article is to evaluate lymphocyte dynamics during and after fingolimod therapy and assess the relationship between lymphocyte counts and infections. METHODS: Lymphocyte counts and their relationship with infections were evaluated in three multiple sclerosis (MS) populations: (Group A) FREEDOMS phase 3 core study group (n = 1272); (Group B) All Studies group (one phase 2 and two phase 3 studies, plus their extensions; n = 2315); and (Group C) Follow-up group (after fingolimod discontinuation; n = 538). RESULTS: Administration of fingolimod 0.5 mg led to reductions in lymphocyte counts to a steady-state of 24%-30% of baseline values within two weeks, which remained stable while on therapy. Following fingolimod discontinuation, average counts exceeded the lower limit of normal range within six to eight weeks, and were 80% of baseline values by three months. In Group A, infection rates per patient-year were 1.4 with placebo and 1.0 in fingolimod-treated patients who had the lowest lymphocyte counts (< 0.2 × 10(9)/l). No evidence was seen for an increase in serious or opportunistic infections. CONCLUSIONS: Fingolimod induces a rapid and reversible reduction in lymphocyte counts without an increase in infections relative to placebo. Because fingolimod reduces blood lymphocyte counts via redistribution in secondary lymphoid organs, peripheral blood lymphocyte counts cannot be utilized to evaluate the lymphocyte subset status of a patient.

6% Hydroxyethyl starch (130/0.4) vs Ringer's lactate preloading before spinal anaesthesia for Caesarean delivery: the randomized, double-blind, multicentre CAESAR trial.

BACKGROUND: Vasopressor administration is recommended to prevent hypotension during spinal anaesthesia (SA) for elective Caesarean delivery. We aimed to test the superior efficacy and ensure safety of a hydroxyethyl starch (HES) vs a Ringer's lactate (RL) preloading, when combined with a phenylephrine-based prophylaxis. METHODS: A total of 167 healthy parturients undergoing elective Caesarean delivery under SA were included in this multicentre, randomized, double-blind study. Patients received 500 ml of 6% HES (130/0.4)+500 ml of RL (HES group) or 1000 ml of RL (RL group) i.v. before SA. After SA, i.v. phenylephrine boluses were titrated when systolic arterial pressure (SAP) was below 95% of baseline. The primary outcome was the incidence of maternal hypotension (SAP <80% of baseline). RESULTS: The incidence of both hypotension and symptomatic hypotension (i.e. with dizziness, nausea/vomiting, or both) was significantly lower in the HES group vs the RL group: 36.6% vs 55.3% (one-sided P=0.025) and 3.7% vs 14.1%. There was no significant difference in total phenylephrine requirements [median (range): 350 (50-1800) vs 350 (50-1250) µg]. The decrease in maternal haemoglobin value the day after surgery was similar in the two groups [1.2 (1.0) vs 1.0 (0.9) g dl(-1)]. There was no detectable placental transfer of HES in six umbilical cord blood samples analysed in the HES group. Neonatal outcomes were comparable between the groups. CONCLUSIONS: Compared with a pure RL preloading, a mixed HES-RL preloading significantly improved prevention of both hypotension and symptomatic hypotension based on early phenylephrine bolus administration and did not induce adverse effects. CLINICAL TRIAL REGISTRATION: NCT00694343 (http://clinicaltrials.gov).

Measurements of semi-volatile organic compounds in settled dust: influence of storage temperature and duration.

Indoor dust samples cannot always be analyzed immediately after collection. However, little information is currently available on how storage conditions may affect measurements. This study was designed to determine how sample storage conditions may affect the concentration of semi-volatile organic compounds (SVOCs) in the dust. A composite dust was prepared using a Standard Reference Material (SRM 2585) with real indoor dust samples. The composite dust was stored in various types of packaging, at different temperatures (-18°C, 5°C, 20°C, and 35°C), and in different light conditions. The concentration of SVOCs was measured after various storage durations. No effect on SVOC concentrations was observed for the composite dust stored in an amber glass vial at -18°C for 36 months. At 5°C, 20°C, and 35°C, losses occurred for the more volatile compounds. The experimental storage conditions clearly showed that temperature and duration affected the concentrations of SVOCs in the composite dust. The type of packaging material (polyethylene zip bag or polyethylene garbage bag) did not seem to have a systematic effect on the preservation of SVOCs in the composite dust. Maximum storage duration times are proposed for each compound at various temperatures. For most compounds, samples can be stored for 2 months at 20°C. For samples that cannot be analyzed immediately, we recommend to store them in the dark at -18°C to ensure a good recovery of all tested compounds.

Assessing the contribution of the chemical exposome to neurodegenerative disease.

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.

Role of recombinant factor VIIa in the clinical management of severe postpartum hemorrhage: consensus among European experts.

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.

Education in obstetric anesthesiology: an international approach.

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.

Pre- and post-natal exposure of children to organophosphate flame retardants: A nationwide survey in France.

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.

Assessing the impact of organ-specific lesion dynamics on survival in patients with recurrent urothelial carcinoma treated with atezolizumab or chemotherapy.

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.

Increase in optic nerve sheath diameter induced by epidural blood patch: a preliminary report.

BACKGROUND: Post-dural puncture headache (PDPH) might be related to cerebrospinal fluid hypotension. Studies in brain-injured patients have shown a good relationship between optic nerve sheath diameter (ONSD) measured by ocular sonography and invasively measured intracranial pressure (ICP). The aim of this study was to evaluate changes in ONSD after lumbar epidural blood patch (EBP). METHODS: Consecutive subjects receiving an EBP for PDPH were included. ONSD and pain measurements were performed before (T(0)), 10 min (M(10)), 2 h (H(2)), and 20 h (H(20)) after the EBP. RESULTS: Ten subjects were included. ONSD [median (inter-quartile range)] increased with time after EBP, from 4.8 mm (4.5-5.1) at T(0) to 5.2 mm (4.9-5.7) at M(10) (P=0.005 vs T(0)), 5.5 mm (5.1-6.0) at H(2) (P=0.007 vs T(0)), and 5.8 mm (5.2-6.3) at H(20) (P=0.02 vs T(0)). EBP was clinically successful in nine of 10 subjects. In subjects in whom EBP was successful, ONSD significantly increased at M(10) and T(2) compared with T(0) (P=0.004 and 0.008, respectively) but did not reach statistical significance at H(20) (P=0.06). In the subject in whom EBP failed, a small increase in ONSD was observed over time. CONCLUSIONS: In this preliminary report, EBP was followed by ONSD enlargement in subjects with successful EBP, but not in the subject with EBP failure. Since ONSD is a surrogate marker of ICP, this suggests that a sustained increase in ICP is associated with successful EBP.