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Background: Significant improvements in survival from out-of-hospital cardiac arrest (OHCA) have been reported; however, these are based only on data from OHCA in whom resuscitation is initiated by emergency medical services (EMS). We aimed to assess the characteristics and temporal trends of OHCA without resuscitation attempt by EMS., Methods: Prospective population-based study between 2011 and 2016 in the Greater Paris area (6.7 million inhabitants). All cases of OHCA were included in collaboration with EMS units, 48 different hospitals, and forensic units., Results: Among 15 207 OHCA (mean age 70.7±16.9 years, 61.6% male), 5486 (36.1%) had no resuscitation attempt by EMS. Factors that were independently associated with increase in likelihood of no resuscitation attempt included: age of patients (odds ratio, 1.06 per year [95% CI, 1.05-1.06], P <0.001), female sex (odds ratio, 1.21 [95% CI, 1.10-1.32], P =0.002), OHCA at home location (odds ratio, 3.38 [95%CI, 2.86-4.01], P <0.001), and absence of bystander (odds ratio, 1.94 [95% CI, 1.74-2.16], P <0.001). Overall, the annual number of OHCA increased by 9.1% (from 2923 to 3189, P =0.028). This increase was related to an increase of the annual number of OHCA without resuscitation attempt by EMS by 26.3% (from 993 to 1253, P =0.012), while the annual number of OHCA with resuscitation attempt by EMS did not significantly change (from 1930 to 1936, P =0.416). Considering only cases with resuscitation attempt, survival rate at hospital discharge increased (from 7.3% to 9.5%, P =0.02). However, when considering all OHCA, survival improvement did not reach statistical significance (from 4.8% to 5.7%, P =0.17)., Conclusions: We demonstrated an increase of the total number of OHCA related to an increase of the number of OHCA without resuscitation attempt by EMS. This increasing proportion of OHCA without resuscitation attempt attenuates improvement in survival rates achieved in EMS-treated patients.

Coronavirus disease 2019 (COVID-19) predisposes to deep vein thrombosis (DVT) and pulmonary embolism (PE) particularly in mechanically ventilated adults with severe pneumonia. The extremely high prevalence of DVT in the COVID-19 patients hospitalized in the intensive care unit (ICU) has been established between 25 and 84% based on studies including systematic duplex ultrasound of the lower limbs when prophylactic anticoagulation was systematically administrated. DVT prevalence has been shown to be markedly higher than in mechanically ventilated influenza patients (6-8%). Unusually high inflammatory and prothrombotic phenotype represents a striking feature of COVID-19 patients, as reflected by markedly elevated reactive protein C, fibrinogen, interleukin 6, von Willebrand factor, and factor VIII. Moreover, in critically ill patients, venous stasis has been associated with the prothrombotic phenotype attributed to COVID-19, which increases the risk of thrombosis. Venous stasis results among others from immobilization under muscular paralysis, mechanical ventilation with high positive end-expiratory pressure, and pulmonary microvascular network injuries or occlusions. Venous return to the heart is subsequently decreased with increase in central and peripheral venous pressures, marked proximal and distal veins dilation, and drops in venous blood flow velocities, leading to a spontaneous contrast "sludge pattern" in veins considered as prothrombotic. Together with endothelial lesions and hypercoagulability status, venous stasis completes the Virchow triad and considerably increases the prevalence of DVT and PE in critically ill COVID-19 patients, therefore raising questions regarding the optimal doses for thromboprophylaxis during ICU stay., Competing Interests: AM reports personal fees from Orion, Servier, Otsuka, Philips, Sanofi, Adrenomed, Epygon, and Fire 1 and grants and personal fees from 4TEEN4, Abbott, Roche, and Sphingotec. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Voicu, Ketfi, Stépanian, Chousterman, Mohamedi, Siguret, Mebazaa, Mégarbane and Bonnin.)

Acipenser stellatus is a critically endangered species due to the anthropic influence. It has been intensively captured for decades because of its high economic value, its roe being used in the caviar industry. Therefore, Acipenser stellatus is intensively raised in fish farms for both conservation and economical purposes. Aquaculture aims to optimize the feeding regime of juveniles in order to improve its profitability. The purpose of this study was to investigate if Acipenser stellatus can adapt to a starvation/refeeding regime by assessing the effects of this regime on oxidative stress biomarkers and antioxidant defense mechanisms in juveniles raised under aquaculture conditions. The juveniles were subjected to two regimes: a 7-day starvation period followed by 21 days of refeeding, respectively a 14-day starvation period followed by 21 days of refeeding. The results showed that both starvation/refeeding regimes induced an enhancement of antioxidant enzymes activities in the intestine of the juveniles. The oxidative damage was counteracted at the protein level. However, lipid peroxidation was significantly induced in the intestine of the juveniles subjected to 14/21-day starvation/refeeding regime. The 7/21-day starvation/refeeding regime proved to be more suitable for Acipenser stellatus and therefore, it could be useful to optimize the feeding practice in aquaculture production.

Objectives: The main objective of this study was to determine the incidence of invasive pulmonary aspergillosis (IPA) in patients with coronavirus disease 2019 (COVID-19) admitted to the intensive care unit (ICU), and to describe the patient characteristics associated with IPA occurrence and to evaluate its impact on prognosis., Methods: We conducted a retrospective cohort study including all successive COVID-19 patients, hospitalized in four ICUs, with secondary deterioration and one or more respiratory samples sent to the mycology department. We used a strengthened IPA testing strategy including seven mycological criteria. Patients were classified as probable IPA according to the European Organization for Research and Treatment of Cancer (EORTC)/Mycoses Study Group Education and Research Consortium (MSGERC) classification if immunocompromised, and according to the recent COVID-19-associated IPA classification otherwise., Results: Probable IPA was diagnosed in 21 out of the 366 COVID-19 patients (5.7%) admitted to the ICU and in the 108 patients (19.4%) who underwent respiratory sampling for deterioration. No significant differences were observed between patients with and without IPA regarding age, gender, medical history and severity on admission and during hospitalization. Treatment with azithromycin for ≥3 days was associated with the diagnosis of probable IPA (odds ratio 3.1, 95% confidence interval 1.1-8.5, p = 0.02). A trend was observed with high-dose dexamethasone and the occurrence of IPA. Overall mortality was higher in the IPA patients (15/21, 71.4% versus 32/87, 36.8%, p < 0.01)., Conclusion: IPA is a relatively frequent complication in severe COVID-19 patients and is responsible for increased mortality. Azithromycin, known to have immunomodulatory properties, may contribute to increase COVID-19 patient's susceptibility to IPA., (Copyright © 2020 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Background: Poisoning is one of the leading causes of admission to the emergency department and intensive care unit. A large number of epidemiological changes have occurred over the last years such as the exponential growth of new synthetic psychoactive substances. Major progress has also been made in analytical screening and assays, enabling the clinicians to rapidly obtain a definite diagnosis., Methods: A committee composed of 30 experts from five scientific societies, the Société de Réanimation de Langue Française (SRLF), the Société Française de Médecine d'Urgence (SFMU), the Société de Toxicologie Clinique (STC), the Société Française de Toxicologie Analytique (SFTA) and the Groupe Francophone de Réanimation et d'Urgences Pédiatriques (GFRUP) evaluated eight fields: (1) severity assessment and initial triage; (2) diagnostic approach and role of toxicological analyses; (3) supportive care; (4) decontamination; (5) elimination enhancement; (6) place of antidotes; (7) specificities related to recreational drug poisoning; and (8) characteristics of cardiotoxicant poisoning. Population, Intervention, Comparison, and Outcome (PICO) questions were reviewed and updated as needed, and evidence profiles were generated. Analysis of the literature and formulation of recommendations were then conducted according to the GRADE ® methodology., Results: The SRLF-SFMU guideline panel provided 41 statements concerning the management of pharmaceutical and recreational drug poisoning. Ethanol and chemical poisoning were excluded from the scope of these recommendations. After two rounds of discussion and various amendments, a strong consensus was reached for all recommendations. Six of these recommendations had a high level of evidence (GRADE 1±) and six had a low level of evidence (GRADE 2±). Twenty-nine recommendations were in the form of expert opinion recommendations due to the low evidences in the literature., Conclusions: The experts reached a substantial consensus for several strong recommendations for optimal management of pharmaceutical and recreational drug poisoning, mainly regarding the conditions and effectiveness of naloxone and N-acetylcystein as antidotes to treat opioid and acetaminophen poisoning, respectively.

Purpose: Early and reliable prognostication after cardiac arrest (CA) remains crucial. We hypothesized that protein-S100B (PS100B) could predict more accurately outcome in the early phase of CA compared with other current biomarkers., Methods: This prospective single-center study included 330 adult comatose non-traumatic successfully resuscitated CA patients, treated with targeted temperature management but not extra-corporeal life support. Lactate, pH, creatinine, NSE, and PS100B were sampled in ICU early after return of spontaneous circulation (ROSC) corresponding to admission (Adm). Serial measurements were also performed at H24 and H48. PS100B was the sole biomarker blinded to physicians., Measurements and Main Results: The median delay between ROSC and first PS100B sampling was 220 min. At admission, all biomarkers were significantly associated with good outcome (CPC1-2; 109 patients) at 3-month follow-up (P ≤ 0.001, except for NSE: P = 0.03). PS100B-Adm showed the best AUC of ROC curves for outcome prediction at 3-month (AUC 0.83 [95%-CI: 0.78-0.88]), compared with other biomarkers (P < 0.0001), while AUC for lactate-Adm was higher than for NSE-Adm. AUC for PS100B-H24 was significantly higher than for other biomarkers except NSE-H24 (P ≤ 0.0001), while AUC for NSE-H24 was higher than for lactate-H24 and pH-H24. AUCs for PS100-H48 and NSE-H48 were significantly higher than for all other biomarkers (P < 0.001). Compared to patients with decreased PS100B values over time, an increasing PS100B value between admission and H24 was significantly associated with poor outcome at 3 months (P = 0.001). No-flow, initial non-shockable rhythm, PS100B-Adm, lactate-Adm, pH-Adm, clinical seizures, and absence of therapeutic hypothermia were independent predictors associated with poor outcome at 3-month in multivariate analysis. Net-Reclassification-Index was 70%, 64%, and 81% when PS100B-Adm was added to the clinical model, to clinical model with NSE-Adm, and to clinical model with standard biological parameters, respectively., Conclusions: Early PS100B compared with other biomarkers was independently correlated with outcome after CA, with an interesting added value., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Aim: Coronary angiogram (CA) may be useful after resuscitated out-of-hospital cardiac arrest (OHCA), but data regarding its benefit in patients with non-shockable initial rhythm without ST-segment elevation is scarce. We aimed to evaluate the prevalence of acute coronary syndrome (ACS) and survival in OHCA patients with non-shockable initial rhythm without ST-segment elevation and compare them to patients with shockable initial rhythm without ST-segment elevation., Methods: Retrospective single-centre study approved by the ethics committee of our institution, including adults successfully resuscitated from OHCA of presumed cardiac cause, undergoing routine CA on admission. Baseline characteristics, angiographic data including presence of ACS and survival were compared between patients with non-shockable and shockable initial rhythm focusing on patients without ST-segment elevation., Results: Among 517 patients included between 2002 and 2018, 311 had no ST-elevation, of whom 179 had non-shockable and 132 shockable initial rhythm. Compared with shockable initial rhythm patients without ST-elevation, non-shockable initial rhythm patients without ST-elevation had longer no-flow duration, 5 (1-10) versus 2 (0-8) min, p = 0.024, more frequent shock requiring vasopressors, 72% versus 47% p < 0.0001, a lower prevalence of ACS, 2 (1%), versus 29 (22%), p < 0.001 and higher mortality, 85% versus 39% (p < 0.0001). Among ACS patients, none survived in the non-shockable without ST-elevation group, while 20 (69%) survived in the shockable rhythm without ST-elevation group., Conclusions: Prevalence of ACS in patients without ST-segment elevation and non-shockable initial rhythm is extremely low, and survival extremely poor, therefore routine emergency CA does not seem beneficial in these patients., (Copyright © 2020. Published by Elsevier B.V.)

Acute kidney injury (AKI) is the major complication of rhabdomyolysis. We aimed to identify the predictive factors for AKI and renal replacement therapy (RRT) requirement in poisoning-associated rhabdomyolysis. We conducted a cohort study including 273 successive poisoned patients (median age, 41 years) who developed rhabdomyolysis defined as creatine kinase (CK) >1000 IU/L. Factors associated with AKI and RRT requirement were identified using multivariate analyses. Poisonings mainly involved psychotropic drugs. AKI occurred in 88 patients (37%) including 43 patients (49%) who required RRT. Peak serum creatinine and CK were weakly correlated ( R 2 = 0.17, p < 0.001). Death (13%) was more frequent after AKI onset (32% vs. 2%, p < 0.001). On admission, lithium overdose (OR, 44.4 (5.3-371.5)), serum calcium ≤2.1 mmol/L (OR, 14.3 (2.04-112.4)), female gender (OR, 5.5 (1.8-16.9)), serum phosphate ≥1.5 mmol/L (OR, 2.0 (1.0-4.2)), lactate ≥ 3.3 mmol/L (OR, 1.2 (1.1-1.4)), serum creatinine ≥ 125 µmol/L (OR, 1.05 (1.03-1.06)) and age (OR, 1.04 (1.01-1.07)) independently predicted AKI onset. Calcium-channel blocker overdose (OR, 14.2 (3.8-53.6)), serum phosphate ≥ 2.3 mmol/L (OR, 1.6 (1.1-2.6)), Glasgow score ≤ 5 (OR, 1.12; (1.02-1.25)), prothrombin index ≤ 71% (OR, 1.03; (1.01-1.05)) and serum creatinine ≥ 125 µmol/L (OR, 1.01; (1.00-1.01)) independently predicted RRT requirement. We identified the predictive factors for AKI and RRT requirement on admission to improve management in poisoned patients presenting rhabdomyolysis.

Objective: Lower extremity bypass surgery remains an important treatment option for patients with critical limb ischemia (CLI), but is resource intensive. We sought to evaluate the cost and Medicare reimbursement for lower extremity bypass surgery in patients with CLI., Methods: Hospital cost accounting systems were queried for total technical and professional costs incurred and reimbursement received for patients with CLI undergoing lower extremity bypass at our center between 2011 and 2017. Patients were identified by assignment to Diagnosis-Related Group (DRG) 252, 253, or 254 (other vascular procedure with major complication/comorbidity, with complication/comorbidity, and without complication/comorbidity, respectively). Additional clinical data were incorporated from the Vascular Quality Initiative clinical registry. For non-Medicare patients, reimbursement was indexed to Medicare rates. Contribution margins (reimbursement minus cost) from technical and professional services were analyzed for each patient and summarized by DRG. We compared technical, professional, and total costs; reimbursement; and contribution margins across DRGs using univariate statistics and evaluated factors associated with total contribution margin using median quantile regression., Results: We analyzed 68 patients with hemodynamically confirmed CLI (46% rest pain, 54% tissue loss), of whom 25% received a prosthetic graft. Mean age was 66.1 ± 11.6 years, 69% were male, 49% diabetic, 44% current smokers, and 4% on dialysis. In general, total infrainguinal bypass cost was adequately compensated for patients assigned only the most complex DRG 252 (median, $2490; interquartile range [IQR], -$1,621 to $10,080). In the majority of patients with less complex DRG 253 (median, -$3,100; IQR, -$8499 to $109) and DRG 254 (median, -$4902; IQR, -$9259 to $1059), reimbursement did not cover the cost of care. Both technical costs and professional costs varied significantly with the complexity of DRG. Although reimbursement from technical services increased alongside increasing complexity of DRG, there was insignificant variation in professional reimbursement as DRG complexity increased. On multivariable modeling, longer length of stay (-$2547 per additional day) and preoperative dialysis (-$5555) were significantly associated with negative margins., Conclusions: For the majority of patients with CLI, current Medicare reimbursement does not adequately cover the cost of providing care after open bypass surgery. As commercial insurers move toward Medicare reimbursement rates, more granular risk stratification profiles are needed to ensure open surgical care for patients with CLI remains financially sustainable., (Copyright © 2020 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Aim: Coronary artery disease (CAD) has recently been emphasized as a major cause of sudden cardiac arrest (SCA) in young adults. We aim to assess the rate of immediate coronary angiography performance in young patients resuscitated from SCA., Methods: From May 2011 to May 2017, all cases of out-of-hospital SCA aged 18-40 years alive at hospital admission were prospectively included in 48 hospitals of the Great Paris area. Cardiovascular causes of SCA were centrally adjudicated, and management including immediate coronary angiography performance was assessed., Results: Out of 3579 SCA admitted alive, 409 (11.4%) patients were under 40 years of age (32.3 ± 6.2 years, 69.7% males), with 244 patients having a definite cause identified. Among those, CAD accounted for 72 (29.5%) cases, of which 64 (88.9%) were acute coronary syndromes. The rate of immediate coronary angiography was only 41.7% compared to 65.1% among those ≥40-years (P < 0.001). During the study period, while the rate of immediate coronary angiography increased from 60.5% to 70.3% (P < 0.001) in patients aged ≥40 years, the rate in patients aged less than 40 years remained stable (43.5% to 45.3%, P = 0.795). Patients younger than 40 years were significantly less likely to undergo immediate coronary angiography (OR = 0.34, 95% CI: 0.25-0.47), although early angiography was associated with survival at hospital discharge (OR = 2.68, 95% CI: 1.21-6.00)., Conclusion: CAD is the first cause of SCA in young adults aged less than 40 years. The observed low rates of immediate coronary angiography suggest a missed opportunity for early intervention., (Copyright © 2019 Elsevier B.V. All rights reserved.)

This article presents a facile synthesis method used to obtain new composite films based on polylactic acid and micro-structured hydroxyapatite particles. The composite films were synthesized starting from a polymeric solution in chloroform (12 wt.%) in which various concentrations of hydroxyapatite (1, 2, and 4 wt.% related to polymer) were homogenously dispersed using ultrasonication followed by solvent evaporation. The synthesized composite films were morphologically (through SEM and atomic force microscopy (AFM)) and structurally (through FT-IR and Raman spectroscopy) characterized. The thermal behavior of the composite films was also determined. The SEM and AFM analyses showed the presence of micro-structured hydroxyapatite particles in the film's structure, as well as changes in the surface morphology. There was a significant decrease in the crystallinity of the composite films compared to the pure polymer, this being explained by a decrease in the arrangement of the polymer chains and a concurrent increase in the degree of their clutter. The presence of hydroxyapatite crystals did not have a significant influence on the degradation temperature of the composite film.

Introduction: In critically ill patients undergoing prolonged mechanical ventilation (MV), the difference in long-term outcomes between patients with or without tracheostomy remains unexplored., Methods: Ancillary study of a prospective international multicentre observational cohort in 21 centres in France and Belgium, including 2087 patients, with a one-year follow-up after admission. We included patients with a MV duration ≥10 days, with or without tracheostomy. We explored the one-year mortality with a classical Cox regression model (adjustment on age, SAPS II, baseline diagnosis and withdrawal of life-sustaining therapies) and a Cox regression model using tracheostomy as a time-dependant variable., Results: 29.5% patients underwent prolonged MV, out of which 25.6% received tracheostomy and 74.4% did not. At one-year, 45.2% patients had died in the tracheostomy group and 51.5% patients had died in the group without tracheostomy (p = 0.001). In the Cox-adjusted regression model, tracheostomy was not associated with improved one-year outcome (HR CI95 0.7 [0.5-1.001], p = 0.051), as well as in the model using tracheostomy as a time-dependent variable (OR CI 95 1 [0.7-1.4], p = 0.9)., Conclusions: In our study, there was no statistically significant difference in the one-year mortality of patients undergoing prolonged MV when receiving tracheostomy or not., Trial Registration: NCT01367093., Competing Interests: Samir Jaber is consultant for Drager, Fisher-Paykel, Xenios and Medtronic. The other authors have no financial disclosures and no conflict of interest to declare about this work. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Objectives: A higher survival rate was observed in Sudden Cardiac Arrest (SCA) occurring during sports activities, although the underlying mechanisms remain unclear. We tested the hypothesis that better initial management, rather than sports per se, may account for the observed better outcomes during sports activities., Methods: Data was taken between May 2011 and March 2016 from a prospective ongoing registry that includes all SCA in Paris and suburbs (6.7 million inhabitants). Sports-related SCA (i.e. SCA occurring during sport activities or within one hour of cessation of the activity) were identified., Results: Over the study period, 13,400 SCA occurred, of which 154 were sports-related (median age: 51.2 years, 96.1% males). At discharge, sports activity was associated with an 8-times higher survival rate (39.7% vs. 5.1%, P < 0.001). Logistic regression showed that after considering potential confounders, including age, gender, SCA location, witness presence, time to response, and initial shockable rhythm, occurrence of SCA during sports was associated with a higher survival rate (OR 1.77, 95% CI 1.14-2.74, P = 0.01). However, after further adjustment for initial basic life support, i.e. bystander CPR and AED use, there was no association between sports setting and survival at hospital discharge (OR 1.43, 95% CI 0.91-2.23, P = 0.12)., Conclusion: Sports-related SCA is a rare event, with an 8-times higher survival rate compared to non-sports-related SCA. Better initial management, including bystander CPR and AED use, rather than sports per se, mainly accounts this difference. This highlights the major importance of population education to basic life support in improving SCA outcome., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Aims: We sought to develop a reproducible animal model for acute myocardial infarction (AMI) in adult atherosclerosis-prone pigs., Methods and Results: A coil was placed in the right coronary artery or the left anterior descending artery in 26 downsized spontaneously hypercholesterolaemic pigs and left untreated until thrombotic occlusion. Then, we crossed the thrombotic occlusion with a guidewire, followed by predilatation, thrombus visualisation with optical coherence tomography (OCT) imaging and, finally, deployment of a stent and repeated OCT. After revascularisation, we calculated the index of microcirculatory resistance (IMR). After a feasibility phase (six animals), acute thrombotic occlusion was achieved in all 20 pigs. Eighteen animals were successfully revascularised and survived until sacrifice. Thrombus formation was confirmed by OCT, measurement of thrombin-antithrombin complexes and pathology examination. Myocardial necrosis was confirmed by troponin T elevation, myocardial staining and pathology examination. Distal thrombotic embolisation and microvascular obstruction were supported by increased IMR and pathology examination., Conclusions: A porcine model of thrombotic occlusion AMI in miniaturised adult spontaneously atherosclerosis-prone pigs is feasible by percutaneous intracoronary placement of a coil. The reperfusion by angioplasty completed this model which mirrors human pathological conditions with myocardial infarction, necrosis and distal embolisation.

Background: Post cardiac arrest shock (PCAS) occurring after resuscitated cardiac arrest (CA) is a main cause of early death. Extracorporeal life support (ECLS) could be useful pending recovery from myocardial failure., Aim: To describe our PCAS population, and the factors associated with initiation of ECLS., Methods: This analysis included 921 patients admitted to two intensive care units between 2005 and 2014 for CA and PCAS; 43 of these patients had ECLS initiated. Neurological and ECLS-related outcomes were gathered retrospectively., Results: The 43 patients treated with ECLS were predominantly (70%) young males with evidence of myocardial infarction on coronary angiography. ECLS was initiated in patients with severe cardiovascular dysfunction (median left ventricular ejection fraction 15% [interquartile range 10-25%]), a median of 9hours [interquartile range 6-16hours] after the CA. At 1 year, eight patients (19%) had survived without neurological disability. Blood lactate and coronary aetiology were associated with neurological outcomes. Logistic regression conducted using 878 controls with PCAS identified age>62 years, location of CA, use of a high dose of adrenaline (>3mg) and blood lactate and serum creatinine concentrations (>5mmol/L and>109μmol/L, respectively) as risk factors for initiation of ECLS., Conclusions: ECLS, as a salvage therapy for PCAS, could be an acceptable alternative for highly-selected patients., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Acipenser stellatus represents a species of great economical interest due to its roe used for caviar production. Therefore, it has been intensively captured for decades and nowadays, this species is on the verge of extinction. As a consequence, Acipenser stellatus is intensively raised in fish farms. Aquaculture is focused on optimizing the feeding regime of juveniles. The aim of this study was to investigate if Acipenser stellatus can adapt to a starvation/refeeding regime by assessing the effects of this regime on growth performance, oxidative stress biomarkers and heat shock protein (hsp) gene expression in juveniles raised under aquaculture conditions. The juveniles were subjected to two starvation/refeeding regimes: a 7-day starvation period followed by 21 days of refeeding, and a14-day starvation period followed by 21 days of refeeding. The results had shown that the juveniles subjected to 7/21-day starvation/refeeding regime presented a complete compensatory growth, they were able to counteract the oxidative stress by enhancing activities of the antioxidant enzymes and they presented no significant changes in hsp gene expression. In contrast, 14/21-day starvation/refeeding regime negatively influenced growth performance, it induced a high level of oxidative stress that was impossible to counteract and it determined major changes in the hsp gene expression level in the liver of Acipenser stellatus. Thus, Acipenser stellatus seems to be able to adapt only to the 7/21-day starvation/refeeding regime that does not threaten the growth performance and the welfare of juveniles. Therefore, it could be useful to optimize the feeding practice in aquaculture production.

Introduction: Surgical telementoring connects expert mentors with trainees performing urgent care in austere environments. However, such environments impose unreliable network quality, with significant latency and low bandwidth. We have developed an augmented reality telementoring system that includes future step visualization of the medical procedure. Pregenerated video instructions of the procedure are dynamically overlaid onto the trainee's view of the operating field when the network connection with a mentor is unreliable., Methods: Our future step visualization uses a tablet suspended above the patient's body, through which the trainee views the operating field. Before trainee use, an expert records a "future library" of step-by-step video footage of the operation. Videos are displayed to the trainee as semitransparent graphical overlays. We conducted a study where participants completed a cricothyroidotomy under telementored guidance. Participants used one of two telementoring conditions: conventional telestrator or our system with future step visualization. During the operation, the connection between trainee and mentor was bandwidth throttled. Recorded metrics were idle time ratio, recall error, and task performance., Results: Participants in the future step visualization condition had 48% smaller idle time ratio (14.5% vs. 27.9%, P < 0.001), 26% less recall error (119 vs. 161, P = 0.042), and 10% higher task performance scores (rater 1 = 90.83 vs. 81.88, P = 0.008; rater 2 = 88.54 vs. 79.17, P = 0.042) than participants in the telestrator condition., Conclusions: Future step visualization in surgical telementoring is an important fallback mechanism when trainee/mentor network connection is poor, and it is a key step towards semiautonomous and then completely mentor-free medical assistance systems.

Circulatory failure following cardiac arrest (CA) requires catecholamine support and occasionally veno-arterial extracorporeal membrane oxygenation (vaECMO). VaECMO-generated blood flow is continuous and retrograde, increasing ventricular stroke work. Our aim was to assess the benefit of a device generating a pulsatile vaECMO flow synchronized with the heart rhythm lowering systolic vaECMO output on the left ventricular ejection fraction (LVEF) and pulmonary capillary pressure (Pcap) after CA. This experimental randomized study in pigs compared standard nonpulsatile vaECMO (control) with pulsatile synchronized vaECMO (study) group using a pulsatility-generating device. After sedation and intubation, ventricular fibrillation was induced by pacing. After 10-min ventricular fibrillation, cardiopulmonary resuscitation was performed for 20 min then vaECMO, defibrillation and 0.15 µg/kg/min intravenous epinephrine infusion were initiated. Hemodynamics, Pcap, LVEF by echocardiography and angiography were measured at baseline and every 30 min after the vaECMO start until vaECMO and epinephrine were stopped (at 120 min), and 30 min later. Baseline hemodynamics did not differ between groups; 120 min after vaECMO initiation, LVEF by echocardiography and angiography was significantly higher in the study than control group 55 ± 19% versus 34 ± 13% (P = 0.042), 50 ± 16% versus 33 ± 12% (P = 0.043), respectively. Pcap decreased from baseline by 4.2 ± 8.6 mm Hg in the study group but increased by 5.6 ± 5.9 mm Hg in the control group (P = 0.043). Thirty minutes later, LVEF remained higher in the study group 44 ± 7% versus 26 ± 11% (P = 0.008) while Pcap did not differ. A synchronized pulsatile device decreasing systolic output from vaECMO improved LVEF and Pcap in a pig model of CA and resuscitation., (© 2018 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.)

T cells compete with malignant cells for limited nutrients within the solid tumor microenvironment. We found that effector memory CD4 T cells respond distinctly from other T cell subsets to limiting glucose and can maintain high levels of interferon-γ (IFN-γ) production in a nutrient-poor environment. Unlike naive (T N ) or central memory T (T CM ) cells, effector memory T (T EM ) cells fail to upregulate fatty acid synthesis, oxidative phosphorylation, and reductive glutaminolysis in limiting glucose. Interference of fatty acid synthesis in naive T cells dramatically upregulates IFN-γ, while increasing exogenous lipids in media inhibits production of IFN-γ by all subsets, suggesting that relative ratio of fatty acid metabolism to glycolysis is a direct predictor of T cell effector activity. Together, these data suggest that effector memory T cells are programmed to have limited ability to synthesize and metabolize fatty acids, which allows them to maintain T cell function in nutrient-depleted microenvironments., (Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Cardiac arrest (CA) without return of spontaneous circulation can be treated with veno-arterial extracorporeal membrane oxygenation (vaECMO) implemented surgically or percutaneously. We performed a study assessing time for vaECMO percutaneous cannulation in the catheterization laboratory., Methods: Single-centre retrospective study in a University hospital without on-site cardiovascular surgery, including patients aged >18 receiving vaECMO for out- or in-hospital refractory CA of presumed cardiac cause between 2010 and 2016, cannulated by interventional cardiologists. Cannulation time using anatomic landmarks vessel puncture and conventional wires (first period) was compared with ultrasound guidance puncture and stiff wires (second period). Data are expressed as medians (interquartile range) and percentages., Results: Forty-six patients were included, age 56 (49-62), 34 in the first period. Shockable initial rhythm occurred in 29 (63%), 36 (78%) had ischemic heart disease and 26 (57%) acute myocardial infarction (AMI). Out-of-hospital refractory CA occurred in 27 (59%) patients. Time from out-of-hospital refractory CA to admission was 100 (80-118) min. Cannulation was successful in 42 (91%) patients. Cannulation time was 14 (10-21) min, 17 (12-26) (first) and 8 (6-12) min (second period), p<0.001. Survival to discharge was 9%. In out-of-hospital versus in-hospital, time from CA to vaECMO was 120 (115-140) versus 82 (58-102) min, p=0.011, survival was 7% (two patients) versus 11% (two patients), p=0.35 respectively. All survivors had shockable initial rhythm., Conclusion: In these refractory CA patients with high prevalence of AMI and good feasibility of percutaneous vaECMO in the catheterization laboratory, cannulation time was shorter using ultrasound guidance and stiff wires., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: Direct stenting is the best method for achieving reperfusion in primary percutaneous coronary intervention (PPCI). We hypothesized that the use of a microcatheter (MC) during PPCI when Thrombolysis in Myocardial Infarction (TIMI) flow ≤ 1 after wire crossing would allow visualization of the downstream artery with an optimal TIMI 3 flow at the end of the procedure., Methods: In this pilot study, PPCI patients with TIMI flow ≤ 1 after wire crossing formed the MC group (n = 60); the MC was positioned in the distal part of the culprit artery and a small amount of contrast was injected through it to determine stent size and length to treat the culprit lesion. The MC group was compared with previous consecutive patients treated using standard PPCI (n = 94; similar characteristics except for the rate of previous percutaneous coronary intervention)., Results: In the MC group, downstream arteries were visualized in 98% of cases and direct stenting was achieved in 72% vs 31% (P < 0.0001). Final TIMI 3 flow was similar in both groups (97%). There was less manual thrombectomy (20% vs 63%; P < 0.001) and bailout glycoprotein IIb/IIIa inhibitor use (6.7% vs 29.8%; P < 0.002). The incidence of major adverse events (death, shock, severe arrhythmia) and left ventricular ejection fraction were similar. The peak cardiac enzymes level was significantly lower in the MC group., Conclusions: The MC strategy appears feasible and safe. It could allow exploring new strategies on the basis of more systematic direct stenting and prepared reperfusion by injecting drugs through the MC before reperfusion., (Copyright © 2017 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Background: Targeted temperature management (TTM) between 32 and 36°C is recommended after out-of-hospital cardiac arrest (OHCA). We aimed to assess the feasibility and safety of the "Esophageal Cooling Device" (ECD) in performing TTM., Patients and Methods: This single-centre, prospective, interventional study included 17 comatose OHCA patients. Main exclusion criteria were: delay between OHCA and return of spontaneous circulation (ROSC)>60min, delay between sustained ROSC and inclusion >360min, known oesophageal disease. A TTM between 32 and 34°C was performed using the ECD (Advanced Cooling Therapy, USA) connected to a heat exchanger console (Meditherm III ® , Gaymar, France), without cold fluids' use. Primary endpoint was feasibility of inducing, maintaining TTM, and rewarming using the ECD alone. Secondary endpoints were adverse events, focusing on potential digestive damages. Results were expressed as median (interquartiles 25-75)., Results: Cooling rate to reach the Target Temperature (33°C-TT) was 0.26°C/h [0.19-0.36]. All patients reached the 32-34°C range with a time spent within the range of 26h [21-28] (3 patients did not reach 33°C). Temperature deviation outside the TT during TTM-maintenance was 0.10°C [0.03-0.20]. Time with deviation >1°C was 0h. Rewarming rate was 0.20°C/h [0.18-0.22]. Among the 16 gastrointestinal endoscopy procedures performed, 10 (62.5%) were normal. Minor oeso-gastric injuries (37.5% and 19%, respectively) were similar to usual orogastric tube injuries. One patient experienced severe oesophagitis mimicking peptic lesions, not cooling-related. No patient among the 9 alive at 3-month follow-up had gastrointestinal complains., Conclusion: ECD seems an interesting, safe, accurate, semi-invasive cooling method in OHCA patients treated with 33°C-TTM, particularly during the maintenance phase., (Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.)

xtracorporeal membrane oxygenation (ECMO) is used in cardiopulmonary resuscitation (CPR) of refractory cardiac arrest. We used a 2×2 study design to compare ECMO versus CPR and epinephrine versus placebo in a porcine model of ischemic refractory ventricular fibrillation (VF). Pigs underwent 5 minutes of untreated VF, 10 minutes of CPR, and were randomized to receive epinephrine versus placebo for another 35 minutes. Animals were further randomized to LAD reperfusion at minute 45 with ongoing CPR versus veno-arterial ECMO cannulation at minute 45 of CPR and subsequent LAD reperfusion. Four-hour survival was improved with ECMO while epinephrine showed no effect.

Background: In treated hypertensives, extreme-dippers with stable coronary artery disease (CAD) exhibit more severe nighttime cardiac ischemia than dippers. After excluding confounding factors such as diabetes, CAD or chronic kidney disease (CKD), we assessed whether subendocardial viability, determined by the Buckberg index, was more significantly impaired in extreme-dippers than in dippers., Methods: Two hundred thirteen consecutive treated hypertensives (156 dippers, 57 extreme-dippers), were included. After 24-hour ambulatory blood pressure (BP) monitoring, patients underwent radial applanation tonometry (with determination of: subendocardial viability ratio [SEVR], central augmentation index [AIx], and pulse pressure amplification [PPamp]), carotid-femoral pulse wave velocity (cfPWV) measurement, and cycle ergometer stress testing., Results: Extreme-dippers showed higher cfPWV (8.99 ± 2.16 vs. 8.29 ± 1.69 m/s, P = 0.014), higher AIx (29.7 ± 9.4 vs. 26.4 ± 10.4%, P = 0.042), lower PPamp (1.22 ± 0.14 vs. 1.30 ± 0.15, P < 0.001), lower SEVR (146 ± 23% vs. 157 ± 26%, P = 0.007), and lower nighttime diastolic BP (DBP) (70 ± 9 vs. 75 ± 9 mm Hg, P < 0.001) than dippers. SEVR and cfPWV were inversely correlated. Among extreme-dippers, women exhibited lower SEVR (138 ± 21% vs. 161 ± 23%, P = 0.004), PPamp (1.16 ± 0.10 vs. 1.31 ± 0.15, P < 0.001), and nighttime DBP (67 ± 8 mm Hg vs. 72 ± 8 mm Hg, P = 0.017) than men., Conclusions: Extreme-dipper treated hypertensives with no history of CAD, diabetes or CKD, present increased aortic stiffness and low PPamp. Furthermore, this is the first demonstration of the greater likelihood of these patients to exhibit impaired subendocardial viability compared to dippers. Extreme-dipper hypertensive patients, women in particular, may have a significantly higher risk of silent myocardial ischemia, thus justifying systematic screening., (© American Journal of Hypertension, Ltd 2017. All rights reserved. For Permissions, please email: journals.permissions@oup.com)

Chitosan CS-tripolyphosphate TPP/hyaluronic acid HA nanohydrogels loaded with gadolinium chelates (GdDOTA ⊂ CS-TPP/HA NGs) synthesized by ionic gelation were designed for lymph node (LN) MRI. In order to be efficiently drained to LNs, nanogels (NGs) needed to exhibit a diameter ϕ < 100 nm. For that, formulation parameters were tuned, using (i) CS of two different molecular weights (51 and 37 kDa) and (ii) variable CS/TPP ratio (2 < CS/TPP < 8). Characterization of NG size distribution by dynamic light scattering (DLS) and asymetrical flow-field-flow-fractionation (AF4) showed discrepancies since DLS diameters were consistently above 200 nm while AF4 showed individual nano-objects with ϕ < 100 nm. Such a difference could be correlated to the presence of aggregates inherent to ionic gelation. This point was clarified by atomic force microscopy (AFM) in liquid mode which highlighted the main presence of individual nano-objects in nanosuspensions. Thus, combination of DLS, AF4 and AFM provided a more precise characterization of GdDOTA ⊂ CS-TPP/HA nanohydrogels which, in turn, allowed to select formulations leading to NGs of suitable mean sizes showing good MRI efficiency and negligible toxicity.

Introduction: Sodium nitroprusside (SNP) enhanced CPR (SNPeCPR) demonstrates increased vital organ blood flow and survival in multiple porcine models. We developed a new, coronary occlusion/ischemia model of prolonged resuscitation, mimicking the majority of out-of-hospital cardiac arrests presenting with shockable rhythms., Hypothesis: SNPeCPR will increase short term (4-h) survival compared to standard 2015 Advanced Cardiac Life Support (ACLS) guidelines in an ischemic refractory ventricular fibrillation (VF), prolonged CPR model., Methods: Sixteen anesthetized pigs had the ostial left anterior descending artery occluded leading to ischemic VF arrest. VF was untreated for 5min. Basic life support was performed for 10min. At minute 10 (EMS arrival), animals received either SNPeCPR (n=8) or standard ACLS (n=8). Defibrillation (200J) occurred every 3min. CPR continued for a total of 45min, then the balloon was deflated simulating revascularization. CPR continued until return of spontaneous circulation (ROSC) or a total of 60min, if unsuccessful. SNPeCPR animals received 2mg of SNP at minute 10 followed by 1mg every 5min until ROSC. Standard ACLS animals received 0.5mg epinephrine every 5min until ROSC. Primary endpoints were ROSC and 4-h survival., Results: All SNPeCPR animals (8/8) achieved sustained ROSC versus 2/8 standard ACLS animals within one hour of resuscitation (p=0.04). The 4-h survival was significantly improved with SNPeCPR compared to standard ACLS, 7/8 versus 1/8 respectively, p=0.0019., Conclusion: SNPeCPR significantly improved ROSC and 4-h survival compared with standard ACLS CPR in a porcine model of prolonged ischemic, refractory VF cardiac arrest., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Purpose: We investigated whether forearm skin blood flow could be improved when a multilayer pulsatile inflatable suit was applied at a low pressure to the lower limbs and abdomen. We hypothesized that a non-invasive purely mechanical stimulation of the lower limbs could induce remote forearm blood flow modifications., Methods: The pulsatile suit induced a sequential compartmentalized low compression (65 mmHg), which was synchronized with each diastole of the cardiac cycle with each phase evolving centripetally (lower limbs to abdomen). Modifications of the forearm skin blood flow were continuously recorded by laser Doppler flowmetry (LDF) at baseline and during the pulsatile suit application. Endothelium-dependent and endothelium-independent vasodilations of the forearm skin microcirculation were measured by LDF in response to a local transdermal iontophoretic application of acetylcholine (ACh-test) and to hyperthermia (hyperT- test)., Results: Twenty-four healthy volunteers, 12 men and 12 women (43±14 years) were included in the study. LDF responses increased 1) under pulsatile suit (97±106%, p.

Background: Despite dual antiplatelet treatment, major ischemic events are common following ST elevation myocardial infarction (STEMI). We aimed to assess high platelet reactivity on aspirin (HPR-aspirin) and its association with P2Y12i (HPR-P2Y12i) during the acute phase of STEMI., Methods: We included all consecutive patients admitted for STEMI treated by primary angioplasty in our center for 1year. All patients received a loading dose followed by a maintenance dose of aspirin (75mg/day) and prasugrel (ticagrelor or clopidogrel if contraindicated). Platelet reactivity was assessed 4±1days and 75±15days after admission using light transmission aggregometry with arachidonic acid (LTA-AA-HPR-aspirin) and VASP (HPR-P2Y12i) to define HPR as well as serum Thromboxane-B2 and LTA-ADP. Major cardiac and cerebrovascular events were recorded for 1year., Results: We included 106 patients - mean age was 61y.o., 76% were male and 20% had diabetes. STEMI was anterior in 52% and LV ejection fraction at discharge was 51±9%. 50% of patients were treated with prasugrel and 34% with ticagrelor. At day 4 after STEMI, HPR-aspirin was found in 26% patients and HPR-P2Y12i in 7%. HPR- both aspirin and P2Y12i was found in 4%. Diabetes and age were predictors of HPR-aspirin. HPR-aspirin was persistent 75days later in 36% patients. At 1year, 7.9% patients had experienced major adverse cardiovascular and cerebrovascular events (MACCE). HPR-aspirin and HPR on both aspirin and P2Y12i were significantly associated with MACCE., Conclusion: HPR-aspirin is frequent just after STEMI and associated with MACCE especially when associated with HPR-P2Y12i., (Copyright © 2016. Published by Elsevier Ltd.)

Aim of the Study: Acute coronary syndrome is one of the main causes of out-of-hospital cardiac arrest (OHCA). OHCA patients are particularly exposed to high platelet reactivity (HPR) under aspirin (ASA) treatment. The aim was to evaluate HPR-ASA in therapeutic hypothermia comatose patients resuscitated from OHCA., Methods and Results: Twenty-two consecutive patients with OHCA of cardiac origin were prospectively included after therapeutic hypothermia and randomized to receive ASA 100mg per day, either intravenously (n=13) or orally via a gastric tube (n=9). ADP inhibitors (prasugrel or, if contra-indicated, clopidogrel) were administered in the event of angioplasty. HPR-ASA was assessed by light transmission aggregometry (LTA) with arachidonic acid (AA) and by the PFA-100(®) system with collagen/epinephrine. Clinical, biological and angiographic characteristics were similar in both groups. Using LTA-AA, maximum aggregation intensity was significantly lower in the intravenous group compared to the oral group (15% vs. 29%, respectively; p=0.04). Overall, 10 patients (45%) had HPR-ASA (38% intravenously vs 56% orally; p=0.7). Similarly, closure time was significantly increased in the IV group (277s vs. 155s, respectively; p=0.04)., Conclusion: This study suggests that impaired response to both intravenous and oral aspirin is frequent in comatose patients resuscitated from OHCA., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Aim: To examine whether pulmonary artery balloon pulsation (PABP) could improve circulatory function in acute myocardial infarction (AMI) in pigs., Methods/results: Ten downsize pigs were sedated and ventilated. AMI was induced by inserting a plug into the left anterior descending artery. A pulsation balloon was placed in the pulmonary artery in all animals. In the treatment group (TG), pulsations began when life-threatening arrhythmia or > 30% drop in mean blood pressure (MBP) or > 40% decrease in cardiac output compared to baseline occurred. Pulsation rate was 120/min, independent of the heartbeat, maintained for 10 min. The control group (CG) received no pulsation. In the TG (n = 5), mean BP after the AMI improved by 7 ± 12 mmHg after 150 min while in the CG, MBP decreased by 17 ± 25 mmHg, P < 0.05; coronary perfusion pressure improved by 8 ± 7 mmHg in the TG but decreased by 15 ± 12 in the CG (P < 0.05). In the CG, cardiac output did not change but in the TG it improved from 3.5 ± 0.9 after the AMI to 4.2 ± 1.1 l/min 150 min after AMI (P < 0.05). The TG required 1.8 ± 0.4 electric shocks for ventricular fibrillation versus 0.8 ± 0.4 in the pulsation group (P < 0.05)., Conclusion: PABP could be useful in the management of AMI due to improved mean arterial BP, coronary perfusion pressure, cardiac output and electrical stability. The mechanism of this effect remains to be determined.

Purpose: Circulatory failure (CF) influences management of out-of-hospital cardiac arrest (OHCA) patients and the decision of circulatory assistance. We performed a study to identify on hospital admission patients at risk for CF-related death., Materials and Methods: This is a single-center study including OHCA patients without obvious extracardiac cause and sustained return of spontaneous circulation, in a retrospective derivation (RC) and prospective validation cohort (PC). Univariate/multivariate logistic regression was used in the RC to determine a score predicting CF-related death (due to rearrest or persistent shock despite adequate fluid and catecholamine treatment). The score was validated in the PC., Results: We included 207 patients in the RC and 96 in the PC. Circulatory failure occurred in 59% of RC and 63% of PC patients (P = .70); 35% in both cohorts died of CF. In multivariate regression, correlates of CF-related death making up the logistic score were arterial pH (P < .0001) and shock requiring catecholamines on admission (P = .0045). In the PC, for a logistic score cut-off of 0.5, sensitivity for CF-related death was 50%; specificity, 92%. Patients with shock and arterial pH less than or equal to 7.11 had a CF-related death probability greater than 0.5., Conclusion: A logistic score based on arterial pH and shock requiring catecholamines on admission can predict CF-related death in OHCA patients., (Copyright © 2015 Elsevier Inc. All rights reserved.)

A number of recent studies have illustrated the active role of food/natural components in the prevention of chronic diseases and in the improvement of the quality of life. In the present study, we aimed to obtain and characterize certain extracts from Vitis vinifera L., Aesculus hippocastanum L. and Curcuma longa L., focusing on their antioxidant effects in vitro . Three vegetal extracts were obtained for each plant: in water, 50% water-alcohol and in 96% ethanol. These extracts were then analyzed for their qualitative composition by high performance thin layer chromatography (HPTLC) and total phenolic content by ultraviolet-visible spectrophotometry (UV-VIS). The antioxidant activity of the extracts was assessed in vitro by 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay; the effects of lipid peroxidation on the cell membrane were evaluated using Jurkat cells in two experimental models: normoglycemic and hyperglycemic medium, in order for the results to be able to be translated into clinical practice. In addition, the resistance of the extracts to acid and alkaline hydrolysis was investigated. The obtained extracts had 0.4-39 µg phenolics/mg total extract. The largest amount of phenolics was found in the Cucurma longa extracts, while the lowest was found in the Aesculus hippocastanum extacts. HPTLC analysis identified the main phenolic compounds in the extracts which were ferulic acid, gallic acid, caffeic acid and coumaric acid, as well as quercetin, kaempferol, apigenin, curcumin, luteolin and esculetin. The Aesculus hippocastanum extracts had a low antioxidant efficacy, while both the Curcuma longa and Vitis vinifera extracts had a high antioxidant activity; the products resulting from alkaline hydrolisis were significantly more efficient in scavenging DPPH radicals compared to the products resulting from acid hydrolisis. The antioxidant effects of the Curcuma longa extracts exerted on the membranes of Jurkat cells were the most prominent under both normal and hyperglycemic conditions. The results of the present study may be translated into clinical practice and demonstrate that Curcuma longa extracts may be effective in both the prevention of diabetes mellitus and in attenuating the development of complications associated with the disease.

Aspirin is the key treatment in the secondary prevention of atherothrombosis. Interindividual variability of response has been linked to a higher risk for ischemic events. The aim of this study was to identify clinical and biologic factors predicting high on-aspirin platelet reactivity (HPR) in a high-risk, "real-world" population of vascular patients. All platelet testing performed from 2011 to 2013 in consecutive patients receiving long-term treatment with aspirin for coronary or cerebrovascular disease was retrospectively analyzed. Indications for platelet testing were recurrent ischemic events or high-risk angioplasty. HPR was defined as aggregation intensity≥20% using light-transmission aggregometry with arachidonic acid 0.5 mg/ml. Collagen-epinephrine platelet function analysis was also performed (threshold<165 seconds). Cardiovascular risk factors, usual biologic parameters, and antiplatelet treatment were recorded. A total of 1,508 patients were included (mean age 63 years, 71% men, 23% with diabetes). Antiplatelet treatment was aspirin alone in 333 patients and dual-antiplatelet therapy in 1,175 patients. HPR was found in 11.1% of patients. In multivariate analysis, independent predictive factors of HPR on light-transmission aggregometry with arachidonic acid were diabetes mellitus (odds ratio [OR] 2.10, 95% confidence interval [CI] 1.39 to 3.16), age (OR 1.25, 95% CI 1.06 to 1.47), fibrinogen level (OR 1.20, 95% CI 1.02 to 1.42), and von Willebrand factor level (OR 1.06, 95% CI 1.03 to 1.09). On light-transmission aggregometry with arachidonic acid and collagen-epinephrine platelet function analysis, fibrinogen remained the main factor associated with HPR (OR 1.33, 95% CI 1.19 to 1.61). Similar results were found in patients treated with aspirin alone or dual-antiplatelet therapy. A fibrinogen level>4.0 g/L was associated with a 3.9-fold increased risk for HPR in patients aged <75 years. In conclusion, fibrinogen level was the major predictor of HPR on aspirin in this large population of high-risk vascular patients., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Objectives: In patients treated with therapeutic hypothermia after out-of-hospital cardiac arrest, two blood gas management strategies are used regarding the PaCO2 target: α-stat or pH-stat. We aimed to compare the effects of these strategies on cerebral blood flow and oxygenation., Design: Prospective observational single-center crossover study., Setting: ICU of University hospital., Patients: Twenty-one therapeutic hypothermia-treated patients after out-of-hospital cardiac arrest more than 18 years old without history of cerebrovascular disease were included., Interventions: Cerebral perfusion and oxygenation variables were compared in α-stat (PaCO2 measured at 37 °C) versus pH-stat (PaCO2 measured at 32-34 °C), both strategies maintaining physiological PaCO2 values: 4.8-5.6 kPa (36-42 torr)., Measurements and Main Results: Bilateral transcranial middle cerebral artery flow velocities using Doppler and jugular vein oxygen saturation were measured in both strategies 18 hours (14-23 hr) after the return of spontaneous circulation. Pulsatility and resistance indexes and cerebral oxygen extraction were calculated. Data are expressed as median (interquartile range 25-75) in α-stat versus pH-stat. No differences were found in temperature, arterial blood pressure, and oxygenation between α-stat and pH-stat. Significant differences were found in minute ventilation (p = 0.006), temperature-corrected PaCO2 (4.4 kPa [4.1-4.6 kPa] vs. 5.1 kPa [5.0-5.3 kPa], p = 0.0001), and temperature-uncorrected PaCO2 (p = 0.0001). No differences were found in cerebral blood velocities and pulsatility and resistance indexes in the overall population. Significant differences were found in jugular vein oxygen saturation (83.2% [79.2-87.6%] vs. 86.7% [83.2-88.2%], p = 0.009) and cerebral oxygen extraction (15% [11-20%] vs. 12% [10-16%], p = 0.01), respectively. In survivors, diastolic blood velocities were 25 cm/s (19-30 cm/s) versus 29 cm/s (23-35 cm/s) (p = 0.004), pulsatility index was 1.10 (0.97-1.18) versus 0.94 (0.89-1.05) (p = 0.027), jugular vein oxygen saturation was 79.2 (71.1-81.8) versus 83.3% (76.6-87.8) (p = 0.033), respectively. However, similar results were not found in nonsurvivors., Conclusions: In therapeutic hypothermia-treated patients after out-of-hospital cardiac arrest at physiological PaCO2, α-stat strategy increases jugular vein blood desaturation and cerebral oxygen extraction compared with pH-stat strategy and decreases cerebral blood flow velocities in survivors.

Aims: On-admission coronary angiogram (CA) with angioplasty (percutaneous coronary intervention, PCI) may improve survival in patients resuscitated from out-of-hospital cardiac arrest (OHCA), but long-term survival data are scarce. We assessed long-term survival in OHCA patients managed with on-admission CA and PCI if indicated and compared survival rates in patients with/without acute coronary syndrome (ACS)., Methods: Retrospective single-centre study including patients aged ≥18 years resuscitated from an OHCA without noncardiac cause, with sustained return of spontaneous circulation, undergoing on-admission CA with PCI if indicated. ACS was diagnosed angiographically. Survival was recorded at hospital discharge and at 5-year follow up. Survival probability was estimated by Kaplan-Meier survival curves., Results: A total of 300 comatose patients aged 56 years (IQR 48-67 years) were included, 36% with ST-segment elevation. All had on-admission CA; 31% had ACS. PCI was attempted in 91% of ACS patients and was successful in 93%. Hypothermia was performed in 84%. Survival to discharge was 32.3%. After discharge, 5-year survival was 81.7 ± 5.4%. Survival from admission to 5 years was 26.2 ± 2.8%. ACS patients had better survival to discharge (40.8%) compared with non-ACS patients (28.5%, p=0.047). After discharge, 5-year survival was 92.2 ± 5.4% for patients with ACS and 73.4 ± 8.6% without ACS (hazard ratio, HR, 2.7, 95% CI 0.8-8.9, p=0.1). Survival from admission to 5 years was 37.4 ± 5.2% for ACS patients, 20.7 ± 3.0%, for non-ACS patients (HR 1.5, 95% CI 1.12-2.0, p=0.0067)., Conclusions: OHCA patients undergoing on-admission CA had a very favourable postdischarge survival. Patients with OHCA due to ACS had better survival to discharge at 5-year follow up than patients with OHCA due to other causes.

We report a case of a fatal massive anterior acute myocardial infarction (AMI) after administration of vitamin K1 for over-anticoagulation following cardioembolism from mechanical mitroaortic valve prostheses associated with atrial fibrillation., (© 2014 Société Française de Pharmacologie et de Thérapeutique.)

Objective: This study sought to determine the rate and potential clinical impact of persistent platelet reactivity (PPR) in unprotected left main (ULMD) stenting., Background: PPR under aspirin or thienopyridines is associated with acute events after angioplasty., Methods: We prospectively included 125 patients referred for ULMD stenting. For the first 64 patients (ALMA-1), angioplasty was performed under aspirin and clopidogrel without platelet reactivity assessment. For the last 61 patients (ALMA-2), platelet reactivity was assessed before angioplasty: in patients with aspirin-related PPR, aspirin twice daily was given and in those with clopidogrel-related PPR, clopidogrel double dose or prasugrel was used., Results: Overall, patients' mean age was 69 ± 13 years, 37% were diabetic, and 37% had non-ST segment elevation myocardial infarction (NSTEMI). Patients' characteristics were similar in both studies with isolated left main in 14% and associated with 1-, 2-, or 3-vessel disease in 23%, 36%, and 27%, respectively. Mean SYNTAX score was 23 ± 9. Procedural characteristics were similar using provisional T stenting in 69%, T stenting in 27%, and other techniques in 4%. In ALMA-2, 28% patients had PPR for aspirin, 29% for clopidogrel, and 8% for both. Aspirin twice daily was given in 28% of patients, clopidogrel double dose in 26%, and prasugrel in 31%. The rate of 1-year major adverse cardiovascular and cerebrovascular events (MACCE) was lower in ALMA-2 versus ALMA-1 (8.2% vs. 20.8%; P = 0.04) as a composite end-point of cardiovascular death or stent thrombosis (0.0% vs. 8.3%; P = 0.02)., Conclusion: PPR under aspirin and thienopyridines is frequent in ULMD stenting and could be related to subsequent major events., (© 2013, Wiley Periodicals, Inc.)

Background: Diabetes is associated with a high rate of events after acute coronary syndrome and percutaneous coronary intervention despite aspirin treatment. Once daily aspirin might not provide 24-hour stable biological efficacy in patients with diabetes. We compared the biological efficacy of the same daily dose of aspirin given either once (OPD) or divided twice per day in a population of diabetic patients with previous coronary artery disease., Methods: Ninety-two consecutive diabetic patients with at least 1 criteria of time-dependent aspirin efficacy, elevated high-sensibility C-reactive protein (hs-CRP), fibrinogen, platelet count, or active smoking were prospectively included. Consecutive patients were randomly treated with 150-mg aspirin daily given either OPD (150 mg in the morning) or twice per day (75 mg in the morning and 75 mg in the evening) in a crossover study. The main outcome was platelet reactivity to arachidonic acid (0.5 mg/mL) measured by light transmission aggregometry at trough level before morning aspirin intake., Results: Mean maximum aggregation intensity triggered by arachidonic acid was 19.7% ± 15.4% on OPD and 11.9% ± 10.4% on twice per day (P < .0001). Biological resistance (maximum aggregation intensity ≥20%) was observed in 42% of patients on OPD and 17% on twice per day (P < .001). Of the 39 patients with biological resistance on OPD, 24 (62%) overcame resistance on twice per day. Of the 16 resistant on twice per day, only 1 patient (6%) overcame resistance on OPD. Results were concordant with global evaluation of platelet reactivity by Platelet Function Analyzer-100. A better twice per day efficacy was independent of clopidogrel cotreatment., Conclusion: In a population of diabetic patients with coronary artery disease and a high risk of time-dependent aspirin resistance, aspirin divided twice per day can significantly decrease the rate of biological loss of efficacy at trough level., (Copyright © 2012 Mosby, Inc. All rights reserved.)