Targeted quantification and untargeted exploration of furan and derivatives in infant food by headspace extraction-gas chromatography-Q Exactive Orbitrap mass spectrometry.

The aim of the present study was to assess the performance and complementarity of methods capable of both quantifying furan, 2-Methylfuran (2-MF) and 3-Methylfuran (3-MF) in infant foods, but also to comprehensively explore other furan derivatives. It is more particularly a question of validating and comparing the couplings of the two headspace extraction methods most used for the analysis of furan compounds - Headspace Solid Phase Microextraction (HS-SPME) and Static HeadSpace (SHS) - with gas chromatography hyphenated to a high-resolution mass detector (Q Exactive-Orbitrap MS) which allows both targeted quantification and suspect screening. Firstly, the accuracy profile approach was implemented to assess, validate and compare HS-SPME- and SHS-GC-Q Exactive-Orbitrap MS for the quantification of furan in two model infant foods, apple puree and first infant formula. SHS-GC-Q Exactive-Orbitrap MS, showed better accuracy (uncertainty < 17.2 % vs 22.5 % for HS-SPME GC-Q Exactive-Orbitrap MS) and better sensitivity (LOQ < 2.8 vs LOQ < 4.0 µg/kg) over a broader validation range (2-100 µg/kg vs 5-100 µg/kg in apple puree). Secondly, SHS-GC-Q Exactive-Orbitrap MS was assessed and validated by accuracy profile for the quantification of 2-MF and 3-MF, with performance close to those for furan except for 3-MF in apple puree. Thirdly, SHS-GC-Q Exactive-Orbitrap MS was used to quantify the levels of these compounds in 20 commercial samples (n = 3) belonging to the four main categories of infant food (infant formulae, fruit purees, infant cereals, vegetable/fish baby meals). Furan was quantified in 75 % of the samples, with maximum levels in the vegetable/fish-based infant foods (up to 127 µg/kg) while 2-MF and 3-MF were quantified in 45 % and 15 % of products respectively, with maximum levels of 14.1 µg/kg in follow-on formula 3rd age and 9.2 µg/kg in apple puree. Finally, SHS- and HS-SPME-GC-Q Exactive-Orbitrap MS data of the 20 infant products were processed in suspect screening mode using Compound DiscovererTM software. Coupling with HS-SPME, it made it possible to identify 13 additional furan derivatives, i.e. 5 more than with SHS. The relevance and safety status of the compounds identified are discussed.

Obstetric units' preparedness to manage critically ill women. The second report from the MaCriCare study.

PURPOSE: We aimed to describe the availability of 31 distinct services and facilities to diagnose, resuscitate, and treat critically unwell obstetric patients. METHODS: Using a network of anesthesiologists, intensive care clinicians, obstetricians, critical care nurses, and midwives (MaCriCare) from September 2021 to January 2022, we conducted a descriptive international multicenter cross-sectional survey in centers with obstetric units (OUs) in the WHO Europe Region. RESULTS: The MaCriCare network covers 26 countries and received 1133 responses, corresponding to 2.5 million annual deliveries. The survey identified significant disparities in the availability of the measured 31 services among the OUs, with some services not immediately available and some not available at all. Point-of-care hemoglobin measurements were lacking in 13.8% of OUs. 15.2% of OUs lacked pointof-care lactate measurement, and 11% lacked transfusion services. 23.8% of OUs lacked the ability to administer hypotensive agent infusions in the labor ward. Samebuilding access to cell saver and thromboelastometry was unavailable to 45.5% and 64.4% of OUs, respectively. Access to invasive ventilation was unavailable to 3.4% of OUs, 11.7% were unable to offer same-building access to non-invasive ventilation, and extracorporeal membranous oxygenation was unavailable to 38.3% of the OUs. CONCLUSION: Critically ill obstetric patients have access to markedly different resources in the WHO Europe Region depending on the OU where they are managed. Consensus on which facilities and services should be universally available is urgently needed.

Efficacy and Safety Analyses of Recombinant Factor VIIa in Severe Post-Partum Hemorrhage.

Background: Despite a range of available treatments, it is still sometimes challenging to treat patients with severe post-partum hemorrhage (sPPH). Objective: This study evaluated the efficacy and safety of recombinant activated factor VIIa (rFVIIa) in sPPH management. Methods: An open-label, multi-center, randomized controlled trial (RCT; NCT00370877) and four observational studies (OS; OS-1 (NCT04723979), OS-2, OS-3, and OS-4) were analyzed regarding efficacy (need for subsequent invasive procedures, including uterine compression sutures, uterine or iliac artery ligations, arterial embolization, or hysterectomy) and safety (incidence of thromboembolic events (TE) and maternal mortality) of rFVIIa for sPPH. The RCT, and OS-1 and OS-2, included a control group of women who did not receive rFVIIa (with propensity score-matching used in OS-1 and OS-2), whereas OS-3 and OS-4 provided descriptive data for rFVIIa-exposed women only. Results: A total of 446 women exposed to rFVIIa and 1717 non-exposed controls were included. In the RCT, fewer rFVIIa-exposed women (50% [21/42]) had an invasive procedure versus non-exposed women (91% [38/42]; odds ratio: 0.11; 95% confidence interval: 0.03-0.35). In OS-1, more rFVIIa-exposed women (58% [22/38]) had an invasive procedure versus non-exposed women (35% [13.3/38]; odds ratio: 2.46; 95% confidence interval: 1.06-5.99). In OS-2, 17% (3/18) of rFVIIa-exposed women and 32% (5.6/17.8) of non-exposed women had an invasive procedure (odds ratio: 0.33; 95% confidence interval: 0.03-1.75). Across all included women, TEs occurred in 1.5% (0.2% arterial and 1.2% venous) of rFVIIa-exposed women and 1.6% (0.2% arterial and 1.4% venous) of non-exposed women with available data. Conclusions: The positive treatment effect of rFVIIa on the RCT was not confirmed in the OS. However, the safety analysis did not show any increased incidence of TEs with rFVIIa treatment.

Preparedness for severe maternal morbidity in European hospitals: The MaCriCare study.

PURPOSE: To evaluate obstetric units (OUs) and intensive care units (ICUs) preparedness for severe maternal morbidity (SMM). METHODS: From September 2021 to January 2022, an international multicentre cross-sectional study surveyed OUs in 26 WHO Europe Region countries. We assessed modified early obstetric warning score usage (MEOWS), approaches to four SMM clinical scenarios, invasive monitoring availability in OUs, and access to high-dependency units (HDUs) and onsite ICUs. Within ICUs, we examined the availability of trained staff, response to obstetric emergencies, leadership, and data collection. RESULTS: 1133 responses were evaluated. MEOWS use was 34.5%. Non-obstetric early warning scores were being used. 21.4% (242) of OUs provided invasive monitoring in the OU. A quarter lacked access to onsite HDU beds. In cases of SMM, up to 13.8% of all OUs indicated the need for transfer to another hospital. The transfer rate was highest (74.0%) in small units. 81.9% of centers provided onsite ICU facilities to obstetric patients. Over 90% of the onsite ICUs provided daily specialist obstetric reviews but lacked immediate access to key resources: 3.4% - uterotonic drugs, 7.5% - neonatal resuscitation equipment, 9.2% - neonatal resuscitation team, 11.4% - perimortem cesarean section equipment. 41.2% reported obstetric data to a national database. CONCLUSION: Gaps in provision exist for obstetric patients with SMM in Europe, potentially compromising patient safety and experience. MEOWS use in OUs was low, while access to invasive monitoring and onsite HDU and ICU facilities was variable. ICUs frequently lacked resources and did not universally collect obstetric data for quality control.

Developing a hyperthermic intraperitoneal chemotherapy (HIPEC) gynecologic oncology program: a Canadian experience.

Hyperthermic intraperitoneal chemotherapy (HIPEC) is a treatment option for epithelial ovarian cancer following cytoreductive surgery. The intraperitoneal spread of the disease makes the peritoneal cavity an ideal target for drug delivery. HIPEC has shown promising results in improving overall survival in epithelial ovarian cancer patients when performed during interval cytoreductive surgery. Recent studies have provided level 1 evidence supporting increased overall survival in stage III ovarian cancer patients treated with HIPEC during interval cytoreduction. Meta-analyses have further confirmed the survival improvement in women receiving HIPEC. Despite its inclusion in guidelines, many centers have been hesitant to implement HIPEC programs due to perceived obstacles, such as increased morbidity, cost, and resource requirements. Studies have shown that morbidity rates are acceptable in selected patients, and the addition of HIPEC to cytoreductive surgery is cost effective. Therefore, the main barrier to implementing HIPEC programs is related to resource requirements and logistics, but with proper preparation, these challenges can be overcome. Establishing a successful HIPEC program requires institutional support, a knowledgeable and dedicated team, adequate resources and equipment, and proper training and audit. This review aims to provide evidence based information to guide the development of successful HIPEC programs, including preoperative, anesthetic, and surgical considerations. It also reviews the different equipment and protocols for the perfusion and common postoperative events.

An observational study of gastric content in women scheduled for cesarean section or operative hysteroscopy.

BACKGROUND: The estimation of gastric content in third trimester pregnant women has already been studied, conclusions remain contradictory. The aim of this study was to compare gastric content in pregnant and non-pregnant women using gastric ultrasound. We performed an observational two-center study of women scheduled for a cesarean section (CS group) and of non-pregnant women scheduled for hysteroscopy (HS group). METHODS: Ultrasound evaluation was performed before surgery with measurement of antral cross-sectional area (CSA) in the semi-recumbent position (SRP), primary outcome, and in the right lateral position (RLD). Gastric fluid volume (GFV) was calculated. Results are expressed as medians (25th and 75th percentiles). Perlas Score was evaluated and expressed as number (percentage). RESULTS: Sixty patients in the CS group and 64 in the HS group were analyzed. Antral CSA (SRP) was greater in the CS group (350 mm2 [236-415] vs. 247 mm2 [180-318]; P=0.001). Antral CSA (RLD) was also significantly greater in the CS group (P=0.027). GFV was not different between groups whether expressed in absolute value (P=0.516) or relative to weight (P=0.946) mL.kg-1. Perlas Score repartition was similar in both groups (P=0.860). Kappa coefficients of concordance between CSA, GFV and Perlas Score were slight or at best fair. CONCLUSIONS: Our study confirmed that antral CSA is increased among pregnant women and outlined that antral CSA should not be used alone in the decision-making process especially when the results of indicators (antral CSA, GFV, and Perlas Grading Score) are discordant.

The exploration of remote simulation strategies for the acquisition of psychomotor skills in medicine: a pilot randomized controlled trial.

Background: Progress in remote educational strategies was fueled by the advent of the COVID-19 pandemic. This pilot RCT explored the efficacy of a decentralized model of simulation based on principles of observational and peer-to-peer learning for the acquisition of surgical skills. Methods: Sixty medical students from the University of Montreal learned the running subcuticular suture in four different conditions: (1) Control group (2) Self-learning (3) Peer-learning (4) Peer-learning with expert feedback. The control group learned with error-free videos, while the others, through videos illustrating strategic sub-optimal performances to be identified and discussed by students. Performance on a simulator at the end of the learning period, was assessed by an expert using a global rating scale (GRS) and checklist (CL). Results: Students engaging in peer-to-peer learning strategies outperformed students who learned alone. The presence of an expert, and passive vs active observational learning strategies did not impact performance. Conclusion: This study supports the efficacy of a remote learning strategy and demonstrates how collaborative discourse optimizes the students' acquisition of surgical skills. These remote simulation strategies create the potential for implantation in future medical curriculum design.Trial Registration: NCT04425499 2020-05-06.

The Role of Collaborative Observational Practice and Feedback-Discourse to Promote Remote Acquisition of Technical Surgical Skills.

INTRODUCTION: Acquisition of technical skills remotely in a decentralized model requires an efficacious way of providing feedback. The primary objective was to test the efficacy of various forms of feedback on the acquisition of surgical skills by medical students. METHODS: Forty volunteers were randomized to four experimental groups, differing from the nature of feedback (free text versus structured) and who provided the feedback (expert versus peer learners). They had to perform sutures and upload attempts on a learning management system to receive interactive feedback. The pretest and retention test performances were assessed. RESULTS: All groups significantly improved from pretests to retention tests; however, participants using checklist showed statistically lower improvements than the other groups, which did not differ from each other. CONCLUSIONS: Remote learners can acquire surgical skills, and most importantly, peers who provide feedback, are as effective as experts if they use open-ended comments and not checklists.

Hyperthermic Intraperitoneal Chemotherapy and Interval Debulking Surgery in Conjunction With Elective Cesarean Delivery.

BACKGROUND: Ovarian cancer is rare during pregnancy. For patients beyond 20 weeks of gestation who choose to continue the pregnancy, neoadjuvant chemotherapy may be initiated, followed by interval debulking surgery. Hyperthermic intraperitoneal chemotherapy (HIPEC) may be used with interval debulking surgery for stage III epithelial ovarian cancer, but data are lacking on its administration in the peripartum period. CASE: We illustrate the case of a 40-year-old patient diagnosed with stage III epithelial ovarian cancer at 27 weeks of gestation who underwent neoadjuvant chemotherapy followed by cesarean delivery at term along with interval debulking surgery and HIPEC. The intervention was well tolerated and resulted in the birth of a healthy neonate. The postoperative period was unremarkable, and the patient is disease-free after 22-months of follow-up. CONCLUSION: We demonstrate the feasibility of peripartum HIPEC. Optimal oncologic care should not be jeopardized by the peripartum state of an otherwise healthy patient.

Hand Sewn Anastomosis Skill Acquisition and In Vivo Transfer Using 3D-Printed Small Bowel Simulator.

INTRODUCTION: General surgery residents need to master the hand-sewn bowel anastomosis (HSBA) technique. However, practice opportunities outside of the operating room are rare, and commercial simulators are often costly. The objective of this study is to assess the efficacy of a new, affordable silicone small bowel simulator, made with a three-dimensional (3D) printed mold, as a training tool to learn this technique. METHODS: This was a single-blinded pilot randomized controlled trial comparing two groups of eight junior surgical residents. All participants completed a pretest using an inexpensive, custom developed 3D-printed simulator. Next, participants randomized to the experimental group practiced the HSBA skill at home (eight sessions), while those randomized to the control group did not receive any hands-on practice opportunities. A posttest was done using the same simulator as for the pretest and practice sessions, and the retention-transfer test was performed on an anesthetized porcine model. Pretests, posttests and retention-transfer tests were filmed and graded by a blinded evaluator using assessments of technical skills, quality of final product, and tests of procedural knowledge. RESULTS: The experimental group significantly improved after practicing with the model (P = 0.01), while an equivalent improvement was not noted in the control group (P = 0.07). Moreover, the experimental group's performance remained stable between the posttest and the retention-transfer test (P = 0.95). CONCLUSIONS: Our 3D-printed simulator is an affordable and efficacious tool to teach residents the HSBA technique. It allows development of surgical skills that are transferable to an in vivo model.

A GABA Receptor Modulator and Semiochemical Compounds Evidenced Using Volatolomics as Candidate Markers of Chronic Exposure to Fipronil in Apis mellifera.

Among the various "omics" approaches that can be used in toxicology, volatolomics is in full development. A volatolomic study was carried out on soil bacteria to validate the proof of concept, and this approach was implemented in a new model organism: the honeybee Apis mellifera. Emerging bees raised in the laboratory in pain-type cages were used. Volatolomics analysis was performed on cuticles, fat bodies, and adhering tissues (abdomens without the digestive tract), after 14 and 21 days of chronic exposure to 0.5 and 1 µg/L of fipronil, corresponding to sublethal doses. The VOCs analysis was processed using an HS-SPME/GC-MS method. A total of 281 features were extracted and tentatively identified. No significant effect of fipronil on the volatolome could be observed after 14 days of chronic exposure. Mainly after 21 days of exposure, a volatolome deviation appeared. The study of this deviation highlighted 11 VOCs whose signal abundances evolved during the experiment. Interestingly, the volatolomics approach revealed a VOC (2,6-dimethylcyclohexanol) that could act on GABA receptor activity (the fipronil target) and VOCs associated with semiochemical activities (pheromones, repellent agents, and compounds related to the Nasonov gland) leading to a potential impact on bee behavior.

Sensory acceptability of antioxidant-based formulations dedicated to mitigate heterocyclic aromatic amines in cooked meat.

In a previous work, we studied the inhibition of heterocyclic aromatic amine formation by natural ingredients rich in antioxidants: caper, oregano, wine and green tea. This present work aimed to assess the sensory impact of the addition of these ingredients in ground beef patties. The best liked formulations were determined by a hedonic scoring. Caper and oregano were not significantly different from the standard, the most appreciated, due to their congruency with cooked meat. Direct dissimilarity assessment was performed to evaluate the overall, gustative and odor differences between formulations. Olfactive differences were evidenced as key drivers of these differences. Standard and caper were close while oregano was found significantly different from them. A fast sensory profiling permitted to evidence that aromatic plant note was discriminant for oregano formulation. Gas chromatography-mass spectrometry/multibooth olfactometry identified the distinctive odor-active compounds of the formulations as pyrazines and sulfide for oregano formulation and ester for caper formulation.

Factors associated with failed epidural blood patch after accidental dural puncture in obstetrics: a prospective, multicentre, international cohort study.

BACKGROUND: Epidural blood patch is commonly used for management of post-dural puncture headache after accidental dural puncture. The primary aim was to determine factors associated with failed epidural blood patch. METHODS: In this prospective, multicentre, international cohort study, parturients ≥18 yr receiving an epidural blood patch for treatment of post-dural puncture headache were included. Failed epidural blood patch was defined as headache intensity numeric rating scale (NRS) score ≥7 in the upright position at 4, 24, or 48 h, or the need for a second epidural blood patch, and complete success by NRS=0 at 0-48 h after epidural blood patch. All others were considered partial success. Multinominal logistic regression was used for statistical analyses with P<0.01 considered statistically significant. RESULTS: In all, 643 women received an epidural blood patch. Complete data to classify failure were available in 591 (91.9%) women. Failed epidural blood patch occurred in 167 (28.3%) patients; 195 (33.0%) were completely successful and 229 (38.7%) partially successful. A total of 126 women (19.8%) received a second epidural blood patch. A statistically significant association with failure was observed in patients with a history of migraine, when the accidental dural puncture occurred between lumbar levels L1/L3 compared with L3/L5 and when epidural blood patch was performed <48 h compared with ≥48 h after accidental dural puncture. In patients having radiological investigations, three intracranial bleeds were diagnosed. CONCLUSIONS: Failed epidural blood patch occurred in 28.3% of women. Independent modifiable factors associated with failure were higher lumbar level of accidental dural puncture and short interval between accidental dural puncture and epidural blood patch. A history of migraine was associated with a higher risk of second epidural blood patch. CLINICAL TRIAL REGISTRATION: NCT02362828.

Guidelines for the management of urgent obstetric situations in emergency medicine, 2022.

OBJECTIVE: To provide recommendations on the management of urgent obstetrical emergencies outside the maternity ward. DESIGN: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: There was significant agreement among the experts on strong recommendations to improve practice in the management of urgent obstetric complications in emergency medicine.

A Canadian single-centre experience with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for abdominal malignancies.

BACKGROUND: Cytoreductive surgery in combination with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) has recently shown promise for the treatment of patients with various types of peritoneal carcinomatosis (PC). However, it is an extensive procedure that is associated with a variety of morbidities. We evaluated the safety and clinical outcomes of CRS-HIPEC performed at our centre. METHODS: Patients with abdominal malignancies who underwent CRS-HIPEC between February 2005 and December 2018 at the Centre hospitalier de l'Université de Montréal (CHUM) were retrospectively reviewed. RESULTS: A total of 141 patients were identified (66 with appendiceal cancer, 62 with colorectal cancer, 10 with mesothelioma and 3 with small intestinal tumours). The median age was 55 years. Median overall survival (OS) was not reached for patients with appendiceal tumours; it was 38.3 months for colorectal cancers. Among patients with colorectal cancer, survival was significantly better for those who received intraperitoneal HIPEC with oxaliplatin (74.9 mo) compared with mitomycin C (29.1 mo) (p = 0.006). Complete cytoreductive surgery and low peritoneal carcinomatosis index were associated with the highest overall survival in patients with appendiceal tumours and those with colorectal tumours. CONCLUSION: CRS-HIPEC can be performed with acceptable morbidity in patients with PC. These results validate the outcomes of previously reported trials, but further prospective trials are warranted to determine which patients will most benefit from the addition of HIPEC to CRS.

Prehabilitation before major abdominal surgery: Evaluation of the impact of a perioperative clinical pathway, a pilot study.

BACKGROUND & OBJECTIVE: Major abdominal surgery morbidity can reach 50%. Prehabilitation has shown promising results in decreasing complications. However, it is unknown if prehabilitation can have a positive effect specifically after major abdominal surgery. The goal of this study was to evaluate the feasibility and safety of a prehabilitation program before major abdominal surgery. METHODS: All patients evaluated for major abdominal surgery between February and April 2018 were eligible. A 4-week trimodal prehabilitation program combining physical therapy, nutritional support and psychological preparation was set up. RESULTS: Among 106 patients evaluated for major abdominal surgery during the study period, 60 were included in the prehabilitation program. No cardiovascular events occurred during prehabilitation. The 6-min walking distance increased significantly (+45 m, increase of 9.3%, p = 0.008) after prehabilitation (and before the operation). Anxiety, depression, and several quality of life (QoL) items improved. Postoperative 90-day mortality and morbidity were 3.4% and 48%, respectively. Median hospital length of stay, and intensive care unit length of stay were 14 and 6 days, respectively. For 19 patients readmitted, the treatment was medical, radiological, or surgical, for 11, 5, and 3 patients, respectively. CONCLUSIONS: Prehabilitation before major abdominal surgery is feasible, safe, and improve patients' functional reserves, QoL, and psychological status.