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Introduction: We describe a case of remitting seronegative symmetrical synovitis with pitting oedema (RS3PE) syndrome following administration of the ChAdOx1-S/nCoV-19 [recombinant] vaccine, suggesting a possible causal link. Case Description: A 72-year-old man presented to his general practitioner with swollen, oedematous hands and legs 2 weeks after receiving a coronavirus vaccine. He had raised inflammatory markers but remained systemically well. He was initially presumed to have cellulitis, but his symptoms persisted despite several courses of antibiotics. Deep vein thromboses, cardiac failure, renal failure and hypoalbuminaemia were ruled out. Upon Rheumatology review, he was diagnosed as having RS3PE syndrome with the Covid vaccine suspected of being an immunogenic trigger. Following initiation of steroid therapy, his symptoms improved dramatically, as is characteristic of RS3PE syndrome. Discussion: The pathophysiology of RS3PE is unclear. It is known to have various triggers and associations including infections, certain vaccines and malignancy. This case highlights that a coronavirus vaccine (ChAdOx1-S/nCoV-19 [recombinant] vaccine) is also a possible trigger. Factors that make the diagnosis likely include an acute onset of symptoms including pitting oedema in a typical distribution, age above 50, and unremarkable autoimmune serology. Other learning points from this case include the importance of antibiotic stewardship and the need to explore non-infectious causes of illness when antibiotics do not improve symptoms. Conclusion: The ChAdOx1-S/nCoV-19 [recombinant] vaccine is a possible trigger of RS3PE. However, the benefits of vaccines against coronavirus outweigh the risks in the majority of patients.

OBJECTIVES The antiarrhythmic effects of dexmedetomidine (DEX) have been suggested, but there are controversial reports on the effectiveness of intraoperative use of DEX to reduce the incidence of postoperative tachyarrhythmia (POT). METHODS From a local European Congenital Heart Surgery Association database, we included patients operated for congenital heart diseases under cardiopulmonary bypass within a 5-year period (2017–2021), during which intraoperative use of high dose of DEX (1–1.4 µg/kg/h) was implemented. A doubly robust matching estimation of the causal effect of DEX on the incidence of POT was conducted. We combined a multimodal estimation model in patients not exposed to DEX (disease risk score) as well as a regression analysis in a matched cohort for patients exposured to DEX. RESULTS From a cohort of 593 surgeries (514 patients) occurring during the study period, doubly matched analysis consisted of the analysis of 426 surgeries conducted under DEX or not (213 per group). The probability of developing POT in patients exposed to DEX was 6.6% (95% confidence interval 0.032–0.099) vs 14.5% (95% confidence interval 0.098–0.193) in the group of patients not exposed to DEX. The doubly robust matched estimation method showed a mean reduction of 8.8% (95% confidence interval −0.137 to −0.023) of POT when DEX is used for intraoperative anaesthesia. CONCLUSIONS The use of high doses of DEX during anaesthesia for congenital heart surgery in neonates and infants is associated with a moderate but significant reduction of POT.

International audience; Background: Immunocompromised children are likely to develop a refractory acute respiratory distress syndrome (ARDS). The usefulness of providing extracorporeal life support (ECLS) to these patients is a subject of debate. The aim of our study was to report the outcomes and to compare factors associated with mortality between immunocompromised and non-immunocompromised children supported with veno-venous ECMO. Methods: We performed a retrospective monocentric study in the French pediatric ECMO center of Armand Trousseau Hospital, including all pediatric patients aged from 1 month to 18 years requiring ECLS for ARDS. Results: Between 2007 and 2018, one hundred and eleven (111) patients underwent ECMO for respiratory failure; among them twenty-five (25) were immunocompromised. Survival rate at 6 months after intensive care discharge was significantly lower for immunocompromised patients compared to non-immunocompromised ones (41.7% vs. 62.8%; p = 0.04). ARDS severity was similar between the 2 groups. Fungal pneumonias were reported only in immunocompromised patients (12.5% versus 0% in the control group; p = 0.001). Bleeding complications were significantly more frequent in the immunocompromised group and blood product transfusions were also more frequently required in this group. Conclusion: Six months after intensive care discharge, survival rate of immunocompromised children supported with ECMO for pediatric ARDS is lower than for nonimmunocompromised patients. But, the expectation for a favorable outcome is real and it is worth it if their condition is likely to be compatible with a good long-term quality of life.

Introduction Accurate medication prescribing perioperatively is an essential component of peri-operative optimisation. Older adults are uniquely vulnerable due to polypharmacy and age-related changes in pharmacokinetics and pharmacodynamics. Barriers to this include the urgency of surgery, unclear drug history and poor knowledge of how to manage the patient’s medications. This quality improvement project aimed to improve the accuracy of regular medications prescribed in older adults undergoing emergency laparotomy. Method Multiple Plan, Do, Study, Act (PDSA) cycles were conducted at Southend University Hospital. Patients over 65 undergoing emergency laparotomy were included. Regular medications were retrospectively analysed to assess whether they were continued or suspended appropriately in the perioperative period, according to UKCPA guidelines. The initial cycle analysed prescribing practices for nine medications which were pre-defined as ‘high risk’ of causing adverse effects when prescribed inappropriately. Subsequent cycles scoped all regular medications. Our interventions aimed to increase conscious prescribing by improving prescriber education. Interventions included introducing joint Geriatrician & Surgeon-led teaching sessions, and dissemination of a poster guide with links to resources to aid decision making. Results First cycle (September—November 2020): 32 patients included. Only 30% of all regular medications were within the ‘high risk’ group; 50% of which were prescribed appropriately. Second cycle (May—July 2021): 26 patients included. 72% appropriately prescribed regular medications. Third cycle (September—October 2021): 13 patients included. Sustained improvement in prescribing accuracy to 75%. Problems identified include 1) delay in prescribing 2) regular medications not prescribed 3) prescribed but not administered. Conclusion Improvement in prescribing accuracy amongst doctors is achievable following education-focused intervention. The goal is active decision making with every drug prescribed. Integrating this inter-departmental teaching session into Induction teaching is a sustainable method to improve prescribing practice. This can be translated to every surgical department.

Introduction The number of older adults having emergency abdominal surgery is increasing nationally. In the last National Emergency Laparotomy Audit (NELA) report, 55% of patients were over 65 and 18% were over 80. The wide disparity in mortality rate between under- and over-65 s has persisted since data began collection in 2013. (NELA Seventh Report, 2021). There is already good evidence in Orthopaedic and Vascular surgery that Geriatrician input can improve outcomes including mortality and length of stay. We introduced a Consultant-led service to review every NELA patient aged 65 and above and review the effect on post-operative outcomes. Method We clinically reviewed NELA qualifying patients aged ≥65 years between September 2020–September 2021. Data including Rockwood Clinical Frailty Score (CFS), NELA mortality risk prediction score, 30-day mortality and discharge destination were analysed. Results In total we reviewed 88 patients in 1 year. The median age was 77.5 (range 64–96) years. The median CFS was 3 (range 1–7). 23% patients had a CFS ≥5. 65% patients had a NELA score > 5% (high risk) including 30% with a NELA Score > 20%. The average NELA score was 13.8%. The overall 30-day mortality rate for our cohort was 5.8%; comprised of 10% and 4.7% for patients with a CFS ≥5 and CFS Conclusion We have demonstrated routine review of NELA patients ≥65 years by a Geriatrician-led service has drastically improved outcomes. The mortality rate for both 1) Overall ≥65 (5.8%) and 2) CFS ≥5 (10%) are significantly lower than the national average of 14.6% (ELF Study, 2021) and 18.6% respectively. Importantly, most of these patients were also able to return to their own home. Further research needs to be done on assessing whether reviewing patients pre-operatively can further improve outcomes.

Defining the best ventilatory settings under ECMO remains a challenging question. Despite a well-defined ARDS treatment before ECMO initiation, there is no recommendation on how to ventilate a patient under ECMO for P-ARDS. Only a few descriptive studies are available on ventilatory settings during respiratory ECMO. We aim at evaluating the usefulness of a protective ventilation bundle under ECMO and its capacity to reduce the ventilatory pressure in our ECMO center.We performed a monocentric retrospective study from January 2007 to December 2018. All children aged from 1 month to 18 years old and requiring an extracorporeal membrane oxygenation for a refractory acute respiratory distress syndrome were included. A protective mechanical ventilation under ECMO bundle has been developed in 2014. We compare the period 1 (before 2014) to the period 2 (after 2014).Eighty-three patient had been included during the study. We reported a significant increase of PEEP and mean pressure respectively at day 3, day 7 and day 14 of ECMO during the period 2. Conversely, the driving pressure were significantly lower in the period 2 at day 3 (p: 0.009), day 7 (p:0.001) and day 14 (p: 0.001). We also shown a strong increase in the use of prone positioning during ECMO in the period 2 (p: 0.01). There was no significant effect of our bundle on the length of mechanical ventilation, of hospitalization and on the survival rate.The implementation of a protective mechanical ventilation bundle during ECMO is usefulness to apply for lower ventilatory pressure and higher use of prone positioning. Nonetheless, the lack of power of our study prevents us from showing its efficacy on outcome criteria.

OBJECTIVE To study the association between precipitous labor (less than 3 hours) and the onset of transient tachypnea in singleton fetuses in cephalic presentation with term vaginal deliveries. METHODS This cohort study included women delivered from 2013 through 2017 in our French tertiary university hospital maternity unit. Inclusion criteria were vaginal delivery of liveborn singleton fetus in cephalic presentation and at term. We compared women with precipitous labor and those with longer labor. The principal endpoint was the rate of transient tachypnea of the newborn (TTN). We investigated risk factors for TTN besides duration of labor. RESULTS Comparison of 2644 women with precipitous labor and 7571 with longer labor showed a lower TTN rate in the precipitous labor group (1.6 vs 2.7%; P=0.003). The association was no longer significant after adjustment for the risk factors identified in the univariate analysis (adjusted OR 0.99, 95% CI 0.64-1.54). Risk factors identified for TTN were non-clear amniotic fluid, shoulder dystocia, umbilical cord encirclement, birth weight less than 2500 g, use of cervical ripening and operative vaginal delivery. CONCLUSION Precipitous labor, lasting less than 3 hours, is not associated with a higher risk of transient tachypnea in term newborns after vaginal delivery.

Aims The National Emergency Laparotomy Audit (NELA) results show that only 28.8% of all patients over 65years having emergency laparotomy had Geriatrician input. Advancing age predisposes to more complex medical needs due to a higher prevalence of co-morbidities, polypharmacy, cognitive impairment, and physiological frailty. Introduction of perioperative geriatrician input has been demonstrated to significantly reduce post-operatively mortality (national average 9.5%, rising to 20-40% in older age). We introduced a Geriatrician led liaison team with the initial aim to reduce 30-day mortality in older patients undergoing emergency laparotomy. Methods Prospective database was maintained of all eligible patients reviewed by the new service. Data on Rockwood Clinical Frailty Score (CFS), NELA risk prediction score, length of stay, mortality and complications were analysed. In this service development pilot we specifically assessed age and frailty demographics, expected mortality, and actual mortality in the cohort. Results All NELA patients 65 and over were reviewed by the service between September and December 2020, 35 in total. Median age 77 years; Median CFS 3 (range 2-6); Median NELA mortality risk 12% (range 0.9%-55.8%). Inpatient mortality was 2.9% and 30-day mortality 2.9% during this study period, compared to 18% in the previous year. Conclusion Our pilot study demonstrates that development of an embedded Geriatrician liaison service for patients undergoing emergency laparotomy is achievable in a district general hospital. Consistent with other larger scale studies we demonstrated significant mortality reduction in older adults undergoing emergency laparotomy with the new service offering enhanced inter-disciplinary Surgical, Critical Care and Geriatrician team-working.

Background: Ten months after its appearance in December 2019, SARS-CoV-2 has infected more than 25 million patients worldwide. Because children were first identified as potential spreaders of the virus, schools were closed in several countries. However, it rapidly became evident that the number of hospitalized children infected by SARS-CoV-2 was dramatically lower than that of adults. To date, only hypotheses have been raised to explain this difference, so it is of great importance to describe the presentation of this disease among children. Here, we describe a wide spectrum of COVID-19 manifestation in children in a dedicated pediatric unit in France. Methods: Patients hospitalized with COVID-19 who were diagnosed on the basis of either positive SARS-CoV-2 RT-PCR in nasopharyngeal swabs and/or typical aspects in chest-computed tomography (CT) were included between March and May 2020 in Paris. Results: Twenty-three patients were included on the basis of positive RT-PCR (n = 20) and/or typical aspects in CT (n = 4). The median age was 4.9 years [0.1&ndash, 17.6]. Patients were grouped by age (&lt, 2 years old: n = 14, 61%, 2&ndash, 10 years old: n = 2, 9%, &gt, 10 years old: n = 7, 30%). Overweight or obesity was reported in only three patients. At presentation, the most frequent symptom in the overall cohort was fever (n = 18, 78%), followed by acute rhinitis (n = 9, 64%) and cough (n = 7, 50%) in the under 2-year-old group and cough (n = 4, 57%), fatigue, dyspnea and abdominal pain (n = 3, 43% each) in the over 10-year-old group. Five patients required ICU treatment, four of whom were aged &gt, 10 years, two presented with acute myocarditis, and two were sickle cell disease patients who presented with acute chest syndrome. Discussion and conclusion: The youngest patients seem to present milder forms of COVID-19 without the need for ICU treatment and with a shorter length of hospitalization. More severe evolutions were observed in teenagers, with, however, favorable outcomes. Given the context of closed schools and confinement, the infection of these children suggests intra-familial transmission that needs to be further assessed. This description might help to understand the intriguing differences in COVID-19 severity across age-classes.

Introduction: Acute respiratory distress syndrome (ARDS) is a common entity in pediatric intensive care and associated with a high mortality rate. When conventional management no longer ensures sufficient oxygenation, it is necessary to use extra-body circulatory assistance (ECMO). The objective of our study was to describe the mechanical ventilation parameters used when implementing extracorporeal circulatory support during the management of an ARDS in paediatrics.Materials and Methods: In a retrospective, mono-centric descriptive study, we included patients aged 0-18 years who had acute respiratory distress syndrome refractory to conventional mechanical ventilation management requiring extracorporeal ECMO assistance. Patients were included over the period 2007 to 2017. The main objective was to describe the mechanical ventilation parameters used during ECMO management. The secondary objective was to assess whether certain mechanical ventilation parameters could be associated with mortality in these patients.Results: 83 patients were included with a median age of 16 months[4 - 44 months], the mortality rate was 41%. Before implantation, 64% of patients received conventional ventilation and 36% by OHF. During the ECMO, the barometric ventilation mode was the most commonly used (73%). The median PEP was 10 cmH2O, the driving pressure was 16 cmH2O and the plateau pressures were less than 30 cmH2O. The comparison between deceased and living patients did not find any statistical difference in age or sex. The presence of immunosuppression was statistically associated with mortality, Odds Ratio 9.5 CI 95%[1.77 - 21.24], p = 0.002. The mean ventilation pressure at D7 of ECMO was significantly higher in the deceased group.Conclusions: Our results suggest that despite ECMO management, the mortality rate of pediatric ARDS remains high. To date, there are no recommendations for mechanical ventilation during the ECMO and it seems necessary to define them.; Introduction : Le syndrome de détresse respiratoire aigue (SDRA) est une entté fréquente en réanimation pédiaitrique et associé à un taux de mortalité important. Lorsque la prise en charge conventionnelle ne permet plus d’assurer une oxygénation suffisante, il est nécessaire de recourir à une assistance circulatoire extra corporelle.( ECMO) . Notre étude avait pour objectif de décrire les paramètres de ventilation mécanique utilisé lors de la mise en place d'une assistance ciruclatoire extracorporelle au cours de la prise en charge d'un SDRA en pédiatrie.Matériels et Méthodes : Dans une étude descriptive rétrospective, mono centrique, nous avons inclus les patients âgés de 0 à 18 ans, qui présentaient un syndrome de détresse respiratoire aigüe réfractaire à la prise en charge conventionnelle par ventilation mécanique nécessitant une assistance extracorporelle par ECMO. Les patients ont été inclus sur la période 2007 à 2017. L’objectif principal était de décrire les paramètres de ventilation mécanique utilisés au cours de la prise en charge par ECMO. L’objectif secondaire était d’évaluer si certains paramètres de ventilation mécanique pouvaient être associés à la mortalité chez ces patients.Résultats : 83 patients ont été inclus avec une médiane d’âge de 16 mois [4 - 44 mois], le taux de mortalité était de 41%. Avant implantation, 64 % des patients bénéficiaient d’une ventilation conventionnelle et 36 % par OHF. Pendant l’ECMO, le mode de ventilation barométrique était le plus utilisé (73%). La PEP médiane était de 10 cmH2O, la pression motrice était de 16 cmH2O et les pressions de plateau inférieures à 30cmH2O. La comparaison entre patients décédés et vivants ne retrouvait pas de différence statistique s’agissant de l’âge ou du sexe. La présence d’une immunodépression, était associé statistiquement à la mortalité, Odds Ratio 9,5 IC 95% [1,77 – 21,24], p = 0,002. La pression moyenne de ventilation à J7 d’ECMO était significativement plus élevée dans le groupe des patients décédés.Conclusions : Nos résultats suggèrent que malgré une prise en charge par ECMO, le taux de mortalité du SDRA pédiatrique reste important. Il n’existe à ce jour pas de recommandations portant sur la ventilation mécanique au cours de l’ECMO et il apparait nécessaire d’en définir.

Background: Carbohydrates play a major role in cell signaling in many biological processes. We have developed a set of glycomimetic drugs that mimic the structure of carbohydrates and represent a novel source of therapeutics for endothelial dysfunction, a key initiating factor in cardiovascular complications. Purpose: Our objective was to determine the protective effects of small molecule glycomimetics against free fatty acid­induced endothelial dysfunction, focusing on nitric oxide (NO) and oxidative stress pathways. Methods: Four glycomimetics were synthesized by the stepwise transformation of 2,5­dihydroxybenzoic acid to a range of 2,5­substituted benzoic acid derivatives, incorporating the key sulfate groups to mimic the interactions of heparan sulfate. Endothelial function was assessed using acetylcholine­induced, endotheliumdependent relaxation in mouse thoracic aortic rings using wire myography. Human umbilical vein endothelial cell (HUVEC) behavior was evaluated in the presence or absence of the free fatty acid, palmitate, with or without glycomimetics (1µM). DAF­2 and H2DCF­DA assays were used to determine nitric oxide (NO) and reactive oxygen species (ROS) production, respectively. Lipid peroxidation colorimetric and antioxidant enzyme activity assays were also carried out. RT­PCR and western blotting were utilized to measure Akt, eNOS, Nrf­2, NQO­1 and HO­1 expression. Results: Ex vivo endothelium­dependent relaxation was significantly improved by the glycomimetics under palmitate­induced oxidative stress. In vitro studies showed that the glycomimetics protected HUVECs against the palmitate­induced oxidative stress and enhanced NO production. We demonstrate that the protective effects of pre­incubation with glycomimetics occurred via upregulation of Akt/eNOS signaling, activation of the Nrf2/ARE pathway, and suppression of ROS­induced lipid peroxidation. Conclusion: We have developed a novel set of small molecule glycomimetics that protect against free fatty acidinduced endothelial dysfunction and thus, represent a new category of therapeutic drugs to target endothelial damage, the first line of defense against cardiovascular disease.

Endothelin-1 (ET-1) is involved in the pathogenesis of cardiac and renal diseases, and in the progression of tumour growth in cancer, but current diagnosis and treatment remain inadequate. Peptides derived from the 212 amino acid precursor preproendothelin-1 (ppET-1) may have utility as biomarkers, or cause biological effects that are unaffected by endothelin receptor antagonists. Here, we used specific immunoassays and LC-MS/MS to identify NT-proET-1 (ppET-1[18–50]), Endothelin-Like Domain Peptide (ELDP, ppET-1[93–166]) and CT-proET-1 (ppET-1[169–212]) in conditioned media from cultured endothelial cells. Synthesis of these peptides correlated with ET-1, and plasma ELDP and CT-proET-1 were elevated in patients with chronic heart failure. Clearance rates of NT-proET-1, ELDP and CT-proET-1 were determined after i.v. injection in anaesthetised rats. CT-proET-1 had the slowest systemic clearance, hence providing a biological basis for it being a better biomarker of ET-1 synthesis. ELDP contains the evolutionary conserved endothelin-like domain sequence, which potentially confers biological activity. On isolated arteries ELDP lacked direct vasoconstrictor effects. However, it enhanced ET-1 vasoconstriction and prolonged the increase in blood pressure in anaesthetised rats. ELDP may therefore contribute to disease pathogenesis by augmenting ET-1 responses.

With the ratification of the COP 21 Paris climate agreement, EU climate change policy entered a new phase with more ambitious climate and energy goals for 2030. The EU electricity sector is witnessing its greatest transformation to date because of the rapid deployment of renewables in the form of wind power and solar photovoltaic (PV). Wind and solar PV have been at the forefront of recent growth in renewables-based capacity, although biomass is by far the largest source of renewables-based energy consumption in the EU today. In 2016, installed wind-power capacity surpassed the capacity of both coal and lignite and became the second biggest electricity source in the EU. In the same year, renewables accounted for nearly 86 % of new electricity capacity. The pace of progress for solar PV since 2010 has been impressive: it achieved in 5 years what was expected to take 15 years. The costs of producing electricity using these technologies have decreased rapidly in recent years. The costs of PV electricity have dropped to less than 0.03 EUR/kWh, making it the technology with the lowest electricity generation costs. To understand what EU renewable electricity is projected to look like in the future, our analysis is based on scenarios that are an essential part of European Commission impact assessments. These scenarios assume that the EU reached its greenhouse gas reduction targets as stated in the 2030 energy and climate strategy and as committed to in the COP21 following a cost-optimal approach. To reach the 30 % overall renewable energy target, in 2030 the EU needs to meet 54 % of its gross electricity generation needs using renewable technologies. It also needs to increase its current final consumption of renewable energy and installed capacity, by 68 % and 75 %, respectively. Towards the 2030 target the PRIMES EUCO projections rely mostly in the deployment of solar technology. Its share in final renewable electricity capacity is projected to reach at least 36%. The PRIMES climate mitigation scenarios (EUCO scenarios) project that wind will be the second biggest source of gross electricity generation in the EU in 2030, accounting for 24 % of gross electricity generation and 45 % of final renewable electricity., JRC.C.2-Energy Efficiency and Renewables

The development of renewable energy sources (RES) is a priority for the EU. EU Member States are free to decide how they support RES, so long as they comply with the rules of the EU energy market. The most common support mechanisms for renewable electricity have been feed-in tariffs and feed-in premiums, but recently competitive auctions are becoming increasingly popular. The integration of increasing amounts of variable renewables, such as wind and solar, in electricity grids requires better balancing supply and demand, more grid interconnections and energy storage. The focus of support for renewables used to be in electricity sector but it is also broadening in heating/cooling and transport sectors., JRC.C.2-Energy Efficiency and Renewables

Mesenchymal stem cells (MSCs) are an attractive cell source for tissue engineering applications due to their multipotentiality and increased expansion potential compared to mature cells. However, the full potential of MSCs for cellular therapies is not realised, due, in part, to premature proliferative senescence and impaired differentiation capacity following expansion under 20% oxygen. Bone marrow MSCs reside under reduced oxygen levels (4%-7% oxygen), thus this study investigates the effects of uninterrupted physiological oxygen tensions (2%, 5%) on MSC expansion and subsequent differentiation. Expansion potential was evaluated from colony formation efficiency, population-doubling rates, and cellular senescence. Colony formation was significantly reduced under 5% oxygen compared to 2% and 20% oxygen. Population-doubling time was initially shorter with 20% oxygen, but subsequently no significant differences in doubling time were detected between the oxygen conditions. MSCs expanded with 20% oxygen contained a greater proportion of senescent cells than those under physiological oxygen levels, indicated by a three to fourfold increase in β-galactosidase staining. This may be related to the approximately twofold enhanced mitochondrial oxygen consumption under this culture condition. Chondrogenic differentiation was achieved following expansion at each oxygen condition. However, osteogenesis was only achieved for cells expanded and differentiated at 20% oxygen, indicated by alkaline phosphatase activity and alizarin red staining. These studies demonstrate that uninterrupted hypoxia may enhance long-term MSC expansion, but results in a population with impaired osteogenic differentiation potential. Thus, novel differentiation conditions are required to enable differentiation to nonchondrogenic lineages using hypoxia-cultured MSCs.