Prognostic value of EndoPredict test in patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative primary breast cancer screened for the randomized, double-blind, phase III UNIRAD trial.

BACKGROUND: The purpose of this study was to evaluate the prognostic value of the multigene EndoPredict test in prospectively collected data of patients screened for the randomized, double-blind, phase III UNIRAD trial, which evaluated the addition of everolimus to adjuvant endocrine therapy in high-risk, hormone receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative early breast cancer. PATIENTS AND METHODS: Patients were classified into low or high risk according to the EPclin score, consisting of a 12-gene molecular score combined with tumor size and nodal status. Association of the EPclin score with disease-free survival (DFS) and distant metastasis-free survival (DMFS) was evaluated using Kaplan-Meier estimates. The independent prognostic added value of EPclin score was tested in a multivariate Cox model after adjusting on tumor characteristics. RESULTS: EndoPredict test results were available for 768 patients: 663 patients classified as EPclin high risk (EPCH) and 105 patients as EPclin low risk (EPCL). Median follow-up was 70 months (range 1-172 months). For the 429 EPCH randomized patients, there was no significant difference in DFS between treatment arms. The 60-month relapse rate for patients in the EPCL and EPCH groups was 0% and 7%, respectively. Hazard ratio (HR) supposing continuous EPclin score was 1.87 [95% confidence interval (CI) 1.4-2.5, P < 0.0001]. This prognostic effect remained significant when assessed in a Cox model adjusting on tumor size, number of positive nodes and tumor grade (HR 1.52, 95% CI 1.09-2.13, P = 0.0141). The 60-month DMFS for patients in the EPCL and EPCH groups was 100% and 94%, respectively (adjusted HR 8.10, 95% CI 1.1-59.1, P < 0.0001). CONCLUSIONS: The results confirm the value of EPclin score as an independent prognostic parameter in node-positive, hormone receptor-positive, HER2-negative early breast cancer patients receiving standard adjuvant treatment. EPclin score can be used to identify patients at higher risk of recurrence who may warrant additional systemic treatments.

Reducing the carbon footprint of general anaesthesia: a comparison of total intravenous anaesthesia vs. a mixed anaesthetic strategy in 47,157 adult patients.

Global warming is a major public health concern. Volatile anaesthetics are greenhouse gases that increase the carbon footprint of healthcare. Modelling studies indicate that total intravenous anaesthesia is less carbon intensive than volatile anaesthesia, with equivalent quality of care. In this observational study, we aimed to apply the findings of previous modelling studies to compare the carbon footprint per general anaesthetic of an exclusive TIVA strategy vs. a mixed TIVA-volatile strategy. This comparative retrospective study was conducted over 2 years in two French hospitals, one using total intravenous anaesthesia only and one using a mixed strategy including both intravenous and inhalation anaesthetic techniques. Based on pharmacy procurement records, the quantity of anaesthetic sedative drugs was converted to carbon dioxide equivalents. The primary outcome was the difference in carbon footprint of hypnotic drugs per intervention between the two strategies. From 1 January 2021 to 31 December 2022, 25,137 patients received general anaesthesia in the hospital using the total intravenous anaesthesia strategy and 22,020 in the hospital using the mixed strategy. The carbon dioxide equivalent footprint of hypnotic drugs per intervention in the hospital using the total intravenous anaesthesia strategy was 20 times lower than in the hospital using the mixed strategy (emissions of 2.42 kg vs. 48.85 kg carbon dioxide equivalent per intervention, respectively). The total intravenous anaesthesia strategy significantly reduces the carbon footprint of hypnotic drugs in general anaesthesia in adult patients compared with a mixed strategy. Further research is warranted to assess the risk-benefit ratio of the widespread adoption of total intravenous anaesthesia.

Ultrasound assessment of gastric contents in children before general anaesthesia for acute appendicitis.

There is increasing evidence that a minority of adults with acute appendicitis have gastric contents, posing an increased risk of pulmonary aspiration. This study aimed to evaluate the proportion of children with acute appendicitis who have gastric contents considered to pose a higher risk of pulmonary aspiration. We analysed point-of-care gastric ultrasound data routinely collected in children before emergency appendicectomy in a specialist paediatric hospital over a 30-month period. Based on qualitative and quantitative antral assessment in the supine and right lateral decubitus positions, gastric contents were classified as 'higher-risk' (clear liquid with calculated gastric fluid volume > 0.8 ml.kg-1 , thick liquid or solid) or 'lower-risk' of pulmonary aspiration. The 115 children studied had a mean (SD) age of 11 (3) years; 37 (32%; 95%CI: 24-42%) presented with higher-risk gastric contents, including 15 (13%; 95%CI: 8-21%) with solid/thick liquid contents. Gastric contents could not be determined in 13 children as ultrasound examination was not feasible in the right lateral decubitus position. No cases of pulmonary aspiration occurred. This study shows that gastric ultrasound is feasible in children before emergency appendicectomy. This technique showed a range of gastric content measurements, which could contribute towards defining the risk of pulmonary aspiration.

Increased incidence of pathogenic variants in ATM in the context of testing for breast and ovarian cancer predisposition.

Pathogenic Variants (PV) in major cancer predisposition genes are only identified in approximately 10% of patients with Hereditary Breast and Ovarian Cancer (HBOC) syndrome. Next Generation Sequencing (NGS) leads to the characterization of incidental variants in genes other than those known to be associated with HBOC syndrome. The aim of this study was to determine if such incidental PV were specific to a phenotype. The detection rates of HBOC-associated and incidental PV in 1812 patients who underwent genetic testing were compared with rates in control groups FLOSSIES and ExAC. The rates of incidental PV in the PALB2, ATM and CHEK2 genes were significantly increased in the HBOC group compared to controls with, respective odds ratios of 15.2 (95% CI = 5.6-47.6), 9.6 (95% CI = 4.8-19.6) and 2.7 (95% CI = 1.3-5.5). Unsupervised Hierarchical Clustering on Principle Components characterized 3 clusters: by HBOC (P = 0.01); by ExAC and FLOSSIES (P = 0.01 and 0.02 respectively); and by HBOC, ExAC and FLOSSIES (P = 0.01, 0.04 and 0.04 respectively). Interestingly, PALB2 and ATM were grouped in the same statistical cluster defined by the HBOC group, whereas CHEK2 was in a different cluster. We identified co-occurrences of PV in ATM and BRCA genes and confirmed the Manchester Scoring System as a reliable PV predictor tool for BRCA genes but not for ATM or PALB2. This study demonstrates that ATM PV, and to a lesser extent CHEK2 PV, are associated with HBOC syndrome. The co-occurrence of ATM PV with BRCA PV suggests that such ATM variants are not sufficient alone to induce cancer, supporting a multigenism hypothesis.

[Reprint of: Severe pre-eclampsia: guidelines for clinical practice from the French Society of anesthesiology and intensive care (SFAR) and the French College of gynaecologists and obstetricians (CNGOF)]. / Republication de : recommandations formalisées d'experts. Prise en charge de la patiente avec une pré-éclampsie sévère­RFE communes Société française d'anesthésie-réanimation (SFAR)­Collège national des gynécologues et obstétriciens français (CGNOF).

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.

Contribution of blood detection of insulin-like growth factor binding protein-1 for the diagnosis of amniotic-fluid embolism: a retrospective multicentre cohort study.

OBJECTIVE: To assess the contribution of maternal blood detection of IGFBP-1 for the diagnosis of amniotic-fluid embolism in clinical daily practice. DESIGN: A retrospective multicentre cohort study. SETTING: Three tertiary care obstetric units in France. SAMPLE: Data of 86 women for whom amniotic-fluid embolism had been suspected and maternal serum detection of IGFBP-1 had been performed between 2011 and 2019 were analysed. METHODS: The criteria defined by the United Kingdom Obstetric Surveillance System (UKOSS) were used for the retrospective diagnosis of amniotic-fluid embolism. The more structured definition proposed by the Society for Maternal-Fetal Medicine and the Amniotic Fluid Embolism Foundation (SMFM) was also used as secondary endpoint. MAIN OUTCOME MEASURES: Agreements between biological and clinical assessments were tested. The performance of blood detection of IGFBP-1 for the diagnosis of amniotic-fluid embolism according to the UKOSS criteria, and to the SMFM definition, was also assessed. RESULTS: There was only slight agreement between clinical and laboratory diagnosis of amniotic-fluid embolism (Cohen's Kappa coefficient: 0.04). Blood detection of IGFBP-1 had a sensitivity of 16%, a specificity of 88%, a positive and a negative likelihood ratio of 1.3 and 0.95, respectively, and a positive and a negative predictive value of 58 and 50%, respectively, for the diagnosis of amniotic-fluid embolism based on the UKOSS criteria. The use of the more structured SMFM definition of amniotic-fluid embolism did not substantially change the results. CONCLUSION: These results question the usefulness of blood detection of IGFBP-1 for the early diagnosis of amniotic-fluid embolism in daily clinical practice. TWEETABLE ABSTRACT: This retrospective multicentre study questions the contribution of IGFBP-1 detection for the diagnosis of AFE.

Ectopic pregnancy management by V-NOTES technique.

Ectopic pregnancy is a frequent and life-threatening risk of childbearing. Its management represents a mainstay of emergency gynecological surgery, and laparoscopy is the surgical gold standard technique. The technique of transvaginal natural orifice transluminal endoscopic surgery (V-NOTES) for the management of ectopic pregnancy is presented herein. The procedure is illustrated by an instructive video article that standardizes the essential steps to make the technique ergonomic and easy to perform (step-by-step explanations). This surgical technique allows to consider vaginal salpingectomy using a combined cœlio-vaginal approach. After a posterior colpotomy, an Alexis retractor was inserted in the pouch of Douglas followed by the placement of a dedicated platform on which three trocars were fixed. Pneumoperitoneum was then achieved. Once the diagnosis of ruptured tubal ectopic pregnancy was established, a salpingectomy was performed. As a minimally invasive approach, this procedure has high patient acceptance and seems to improve favorable clinical outcomes.

[Normal childbirth: physiologic labor support and medical procedures. Guidelines of the French National Authority for Health (HAS) with the collaboration of the French College of Gynaecologists and Obstetricians (CNGOF) and the French College of Midwives (CNSF) -- Text of the Guidelines (short text)]. / Accouchement normal : accompagnement de la physiologie et interventions médicales. Recommandations de la Haute Autorité de Santé (HAS) avec la collaboration du Collège National des Gynécologues Obstétriciens Français (CNGOF) et du Collège National des Sages-Femmes de France (CNSF) ­ Texte des recommandations (texte court).

OBJECTIVE: The objective of these guidelines is to define for women at low obstetric risk modalities that respect the physiology of delivery and guarantee the quality and safety of maternal and newborn care. METHODS: These guidelines were made by a consensus of experts based on an analysis of the scientific literature and the French and international recommendations available on the subject. RESULTS: It is recommended to conduct a complete initial examination of the woman in labor at admission (consensus agreement). The labor will be monitored using a partogram that is a useful traceability tool (consensus agreement). A transvaginal examination may be offered every two to four hours during the first stage of labor and every hour during the second stage of labor or before if the patient requests it, or in case of a warning sign. It is recommended that if anesthesia is required, epidural or spinal anesthesia should be used to prevent bronchial inhalation (grade A). The consumption of clear fluids is permitted throughout labor in patients with a low risk of general anesthesia (grade B). It is recommended to carry out a "low dose" epidural analgesia that respects the experience of delivery (grade A). It is recommended to maintain the epidural analgesia through a woman's self-administration pump (grade A). It is recommended to give the woman the choice of continuous (by cardiotocography) or discontinuous (by cardiotocography or intermittent auscultation) monitoring if the conditions of maternity organization and the permanent availability of staff allow it and, after having informed the woman of the benefits and risks of each technique (consensus agreement). In the active phase of the first stage of labor, the dilation rate is considered abnormal if it is less than 1cm/4h between 5 and 7cm or less than 1cm/2h above 7cm (level of Evidence 2). It is then recommended to propose an amniotomy if the membranes are intact or an oxytocin administration if the membranes are already ruptured, and the uterine contractions considered insufficient (consensus agreement). It is recommended not to start expulsive efforts as soon as complete dilation is identified, but to let the presentation of the fetus drop (grade A). It is recommended to inform the gynecologist-obstetrician in case of nonprogression of the fetus after two hours of complete dilation with sufficient uterine dynamics (consensus agreement). It is recommended not to use abdominal expression (grade B). It is recommended to carry out preventive administration of oxytocin at 5 or 10 IU to prevent PPH after vaginal delivery (grade A). In the case of placental retention, it is recommended to perform a manual removal of the placenta (grade A). In the absence of bleeding, it should be performed 30minutes but not more than 60minutes after delivery (consensus agreement). It is recommended to assess at birth the breathing or screaming, and tone of the newborn to quickly determine if resuscitation is required (consensus agreement). If the parameters are satisfactory (breathing present, screaming frankly, and normal tonicity), it is recommended to propose to the mother that she immediately place the newborn skin-to-skin with her mother if she wishes, with a monitoring protocol (grade B). Delayed cord clamping is recommended beyond the first 30seconds in neonates, not requiring resuscitation (grade C). It is recommended that the first oral dose (2mg) of vitamin K (consensus agreement) be given systematically within two hours of birth. CONCLUSION: These guidelines allow women at low obstetric risk to benefit from a better quality of care and optimal safety conditions while respecting the physiology of delivery.

[Normal childbirth: physiologic labor support and medical procedures. Guidelines of the French National Authority for Health (HAS) with the collaboration of the French College of Gynaecologists and Obstetricians (CNGOF) and the French College of Midwives (CNSF) - Mother's wellbeing and regional or systemic analgesia for labor]. / Accouchement normal : accompagnement de la physiologie et interventions médicales. Recommandations de la Haute Autorité de Santé (HAS) avec la collaboration du Collège National des Gynécologues Obstétriciens Français (CNGOF) et du Collège National des Sages-Femmes de France (CNSF) ­ Bien être maternel et prise en charge médicamenteuse de la douleur.

INTRODUCTION: These guidelines deal with the parturient wellbeing in terms of hydration and regional and systemic pain management during labour. METHOD: Guidelines were established based on literature analysis and experts consensus. RESULTS: Clear liquids consumption is permitted all along labor and postpartum, without volume limitation, in patients at low risk of general anesthesia (grade B). The consumption of solid foods is not recommended during the active stage of labor (consensus agreement). It is recommended to promote on regional analgesia to prevent inhalation (grade A). Pain relief using regional analgesia is a part of normal childbirth. It is recommended to provide regional analgesia to parturient who wish these technics. Regional analgesia is the safest and most effective analgesic method for the mother (grade A) and the child (grade B). It is recommended to inform women on the analgesic technics, to respect their choice and consider the right for a parturient to change her strategy in obstetrical circumstances or in cases of untractable pain (consensus agreement). It is recommended to perform a "low-dose" regional analgesia that respects the experience of childbirth (grade A) and maintain it with a patient controlled epidural analgesia technics (grade A). There is no minimum cervical dilation to allow epidural analgesia (grade A). In cases of rapid labor or after delivery for revision, spinal or combined spinal epidural can be used (grade C). Epidural has not to be ended before birth (consensus agreement). Blood pressure and fetal heart rate must be monitored every 3minutes after induction and/or each 10mL bolus then hourly (consensus agreement). Systematic and preventive fluid loading is not needed if only due to regional analgesia (grade B). Deambulation or postures are allowed in the absence of motor block and must be traced and do not alter the distribution of the regional analgesia (grade C). The postures of childbirth do not alter regional analgesia spread (NP2). There is no effect low dose regional analgesia on the duration of obstetric labor, nor the rate of instrumental births or caesarean section (NP1). Systematic use of oxytocin due to epidural analgesia is neither useful nor recommended (AE). Regional analgesia has no side effect on the fetus or newborn (NP1). If regional analgesia is contraindicated or during the waiting time, alternatives analgesic drugs (entonox, nalbuphine and tramadol or pudendal block) can be used but their analgesic efficiency remains mediocre to moderate and they are associated with adverse maternal and especially neonatal side effects (NP2). Remifentanil, ketamine and volatile anesthetics are excluded from these recommendations. CONCLUSION: The present guidelines were established to update wellbeing of normal parturient during normal labor: hydration is recommended and low dose patient-controlled regional (epidural and spinal) analgesia is the most effective and safest analgesic method.

Need for risk-adapted therapy for malignant ovarian germ cell tumors: A large multicenter analysis of germ cell tumors' patients from French TMRG network.

BACKGROUND: Malignant ovarian germ cell tumors are rare tumors, affecting young women with a generally favorable prognosis. The French reference network for Rare Malignant Gynecological Tumors (TMRG) aims to improve their management. The purpose of this study is to report clinicopathological features and long-term outcomes, to explore prognostic parameters and to help in considering adjuvant strategy for stage I patients. PATIENTS AND METHODS: Data from patients with MOGCT registered among 13 of the largest centers of the TMRG network were analyzed. We report clinicopathological features, estimated 5-year event-free survival (5y-EFS) and 5-year overall survival (5y-OS) of MOGCT patients. RESULTS: We collected data from 147 patients including 101 (68.7%) FIGO stage I patients. Histology identifies 40 dysgerminomas, 52 immature teratomas, 32 yolk sac tumors, 2 choriocarcinomas and 21 mixed tumors. Surgery was performed in 140 (95.2%) patients and 106 (72.1%) received first line chemotherapy. Twenty-two stage I patients did not receive chemotherapy. Relapse occurred in 24 patients: 13 were exclusively treated with upfront surgery and 11 received surgery and chemotherapy. 5y-EFS was 82% and 5y-OS was 92.4%. Stage I patients who underwent surgery alone had an estimated 5y-EFS of 54.6% and patients receiving adjuvant chemotherapy 94.4% (P < .001). However, no impact on estimated 5y-OS was observed: 96.3% versus 97.8% respectively (P = .62). FIGO stage, complete primary surgery and post-operative alpha fetoprotein level significantly correlated with survival. CONCLUSION: Adjuvant chemotherapy does not seem to improve survival in stage I patients. Active surveillance can be proposed for selected patients with a complete surgical staging.

Infrared thermography to assess dermatomal levels of labor epidural analgesia with 1 mg/mL ropivacaine plus 0.5 µg/mL sufentanil: a prospective cohort study.

BACKGROUND: Assessment of the effectiveness of obstetric epidural analgesia may be difficult and techniques for objective assessment of epidural spread of local anesthetic would be useful. In this prospective cohort study we assessed whether obstetric epidural analgesia from a low concentration of ropivacaine led to significant change in cutaneous temperature, related to sympathetic block detected by infrared thermography, at dermatomes C4, T4, T10, L2 and L5. METHODS: Women in spontaneous labor who requested epidural analgesia were consecutively recruited. Epidural analgesia was induced with a bolus of 10-15 mL of ropivacaine 1 mg/mL and sufentanil 0.5 µg/mL, followed by continuous epidural infusion. Skin temperature was measured using thermography before and 20 min after the epidural bolus. The verbal pain score using a numeric rating scale was recorded before and 60 min after the epidural bolus. The upper sensory block to cold sensation was tested 30 and 60 min after the bolus by a physician blinded to the skin temperature. Failed epidural analgesia was defined as verbal pain score >3 at 60 min. RESULTS: Fifty-three parturients were included and analyzed. We found a significant increase in skin temperatures measured at T4, T10, L2 and L5 dermatomes, but not at C4, and a significant difference in the change in skin temperature at T10 between failed (n=3) and successful (n=50) epidural analgesia. CONCLUSIONS: These results suggest that infrared thermography might be useful for the early diagnosis of successful obstetric epidural analgesia.

Reliability of gastric suctioning compared with ultrasound assessment of residual gastric volume: a prospective multicentre cohort study.

We aimed to compare the reliability of aspiration via a nasogastric tube with ultrasound for assessment of residual gastric volume. Sixty-one adult patients who were mechanically ventilated and received continuous enteral feeding through a nasogastric tube for > 48 h were included. A first qualitative and quantitative ultrasound examination of the gastric antrum was followed by gastric suctioning, performed by an operator blinded to the result of the ultrasound examination. A second ultrasound examination was performed thereafter, followed by re-injection of the aspirated gastric contents (≤ 250 ml) into the stomach. A third ultrasound assessment was then immediately performed. If the suctioned volume was ≥ 250 ml, 250 mg erythromycin was infused over 30 min. A fourth ultrasound was performed 90 min after the third. Sixty (98%) patients had a qualitatively assessed full stomach at first ultrasound examination vs. 52 (85%) after gastric suctioning (p = 0.016). The calculated gastric volume significantly decreased after gastric suctioning, without a significant decrease in the number of patients with volume ≥ 250 ml. Four of the nine patients with calculated gastric volume ≥ 250 ml had vomiting within the last 24 h (p = 0.013). The antral cross-sectional area significantly decreased between the third and the fourth ultrasound examination (p = 0.015). Erythromycin infusion did not make a significant difference to gastric volume (n = 10). Our results demonstrate that gastric suctioning is not a reliable tool for monitoring residual gastric volume. Gastric ultrasound is a feasible and promising tool for gastric volume monitoring in clinical practice.

Effect of body position on qualitative and quantitative ultrasound assessment of gastric fluid contents.

We assessed the impact of raising the upper section of the bed, and patient positioning, on ultrasound assessment of gastric fluid contents. We performed ultrasound examinations in 25 subjects lying on their back, left and right sides at bed angles of 0°, 30°, 45° and 90°; this was carried out while the subjects were fasted, and repeated 10 min after drinking ≥ 50 ml water. After drinking, gastric contents were detected more frequently in the 45° semirecumbent position compared with the supine and 30° positions. The diagnostic performance of the Perlas qualitative grading scale to detect gastric fluid volume > 1.5 ml.kg-1 was improved at 45°, compared with 0° and 30° angles. The use of a composite ultrasound grading scale at a 45° angle was associated with the best performance, with a sensitivity and specificity of 82%. Antral cross-sectional area was significantly increased when measured in the right lateral position, but there was no effect of raising the bed. In conclusion, raising the upper section of the bed significantly affected qualitative assessment of gastric fluid contents. Further studies are required to determine the most appropriate composite ultrasound grading scale and bed angle for fast and reliable qualitative ultrasound detection of fluid volumes > 1.5 ml.kg-1 .