Association between cardiopulmonary resuscitation duration and survival after out-of-hospital cardiac arrest according: a first nationwide study in France.

OBJECTIVE: Determining whether to pursue or terminate resuscitation efforts remains one of the biggest challenges of cardiopulmonary resuscitation (CPR). No ideal cut-off duration has been recommended and the association between CPR duration and survival is still unclear for out-of-hospital cardiac arrest (OHCA). The aim of this study was to assess the association between CPR duration and 30-day survival after OHCA with favorable neurological outcomes according to initial rhythm. METHODS: This was an observational, retrospective analysis of the French national multicentric registry on cardiac arrest, RéAC. The primary endpoint was neurologically intact 30-day survival according to initial rhythm. RESULTS: 20,628 patients were included. For non-shockable rhythms, the dynamic probability of 30-day survival with a Cerebral Performance Category (CPC) of 1 or 2 was less than 1% after 25 min of CPR. CPR duration over 10 min was not associated with 30-day survival with CPC of 1 or 2 (adjusted OR: 1.67; CI 95% 0.95-2.94). For shockable rhythms, the dynamic probability of 30-day survival with a CPC score of 1 or 2, was less than 1% after 54 min of CPR. CPR duration of 21-25 min was still associated with 30-day survival and 30-day survival with a CPC of 1 or 2 (adjusted OR: 2.77; CI 95% 2.16-3.57 and adjusted OR: 1.82; CI 95% 1.06-3.13, respectively). CONCLUSIONS: Survival decreased rapidly with increasing CPR duration, especially for non-shockable rhythms. Pursuing CPR after 25 min may be futile for patients presenting a non-shockable rhythm. On the other hand, shockable rhythms might benefit from prolonged CPR.

Out-of-hospital cardiac arrests occurring at school in France: A nation-wide retrospective cohort study from the RéAC registry.

AIM: We sought to describe the characteristics of at-school out-of-hospital cardiac arrests cases, subsequent basic life support, as well as ultimate patient outcomes. METHODS: This was a nation-wide, multicentre, retrospective cohort study from the French national population-based RéAC out-of-hospital cardiac arrest registry (July 2011 - March 2023). We compared the characteristics and outcomes of cases occurring at schools vs. in other public places. RESULTS: Of the 149,088 national out-of-hospital cardiac arrests, 25,071 were public: 86 (0.3%) and 24,985 (99.7%) in schools and other public places, respectively. At-school out-of-hospital cardiac arrests, in comparison to other public places, were: significantly younger (median: 42.5 vs. 58 years, p < 0.001); more commonly of a medical cause (90.7% vs. 63.8%, p < 0.001), more commonly bystander-witnessed (93.0% vs. 73.4%, p < 0.001) and recipients of bystander cardiopulmonary resuscitation (78.8% vs. 60.6%, p = 0.001) with shorter median no-flow durations (2 min. vs. 7 min.); with greater bystander automated external defibrillator application (38.9% vs. 18.4%) and defibrillation (23.6%, vs. 7.9%; all p < 0.001). At-school patients had greater rates of return of spontaneous circulation than out-of-school ones (47.7%, vs. 31.8%; p = 0.002), higher rates of survival at arrival at hospital (60.5% vs. 30.7%; p < 0.001) and at 30-days (34.9% vs. 11.6%; p < 0.001), and survival with favourable neurological outcomes at 30 days (25.9% vs. 9.2%; p < 0.001). CONCLUSION: At-school out-of-hospital cardiac arrests were rare in France, however demonstrated favourable prognostic features and outcomes. The use of automated external defibrillators in at-school cases, while more common than cases occurring elsewhere, should be improved.

Bystander basic life support and survival after out-of-hospital cardiac arrest: A propensity score matching analysis.

INTRODUCTION AND OBJECTIVES: In out-of-hospital cardiac arrest, early recognition, calling for emergency medical assistance, and early cardiopulmonary resuscitation are acknowledged to be the three most important components in the chain of survival. However, bystander basic life support (BLS) initiation rates remain low. The objective of the present study was to evaluate the association between bystander BLS and survival after an out-of-hospital cardiac arrest (OHCA). METHODS: We conducted a retrospective cohort study of all patients with OHCA with a medical etiology treated by a mobile intensive care unit (MICU) in France from July 2011 to September 2021, as recorded in the French National OHCA Registry (RéAC). Cases in which the bystander was an on-duty fire fighter, paramedic, or emergency physician were excluded. We assessed the characteristics of patients who received bystander BLS vs. those who did not. The two classes of patient were then matched 1:1, using a propensity score. Conditional logistic regression was then used to probe the putative association between bystander BLS and survival. RESULTS: During the study, 52,303 patients were included; BLS was provided by a bystander in 29,412 of these cases (56.2%). The 30-day survival rates were 7.6% in the BLS group and 2.5% in the no-BLS group (p < 0.001). After matching, bystander BLS was associated with a greater 30-day survival rate (odds ratio (OR) [95% confidence interval (CI)] = 1.77 [1.58-1.98]). Bystander BLS was also associated with greater short-term survival (alive on hospital admission; OR [95%CI] = 1.29 [1.23-1.36]). CONCLUSIONS: The provision of bystander BLS was associated with a 77% greater likelihood of 30-day survival after OHCA. Given than only one in two OHCA bystanders provides BLS, a greater focus on life saving training for laypeople is essential.

Long-term follow-up of survivors of a first acute coronary syndrome: Results from the French MONICA registries from 2009 to 2017.

AIM: The objectives of the study were to characterize the long-term risk of first recurrence of acute coronary syndrome (ACS) among survivors of an incident ACS, as a function of the STEMI/NSTEMI/UA diagnosis. METHODS: Men and women (aged 35-74) hospitalized between 2009 and 2016 for an incident ACS in the French MONICA registries and still alive on discharge were followed-up until December 2017. Recurrent events were defined as the first (non-fatal or fatal) ACS occurring after hospital discharge from the incident event. RESULTS: The study comprised 15,739 incident ACSs with 63,777 patient-years of follow-up. The cumulative probability [95% confidence interval] of recurrent ACS was 6.7% [6.3-7.1%] at 1 year and 18.4% [17.4-19.5%] at 9 years. The cumulative probability of fatal recurrent ACS was 1.4% [1.2-1.5%] at 1 year and 4.3% [3.6-4.9%] at 9 years. The risk of recurrence did not depend on the type of the incident ACS after adjustment for confounding factors. The most frequent forms of recurrence were NSTEMI and UA. The presence of a major complication (OR = 1.59) and an impaired left ventricular ejection fraction (LVEF) (OR > 1.26) increased the risk of recurrence. The annual 1-year recurrence rates decreased from 7.4% in 2009 to 4.0% in 2016 (p < 0.001). CONCLUSION: The recurrence rate after an incident ACS remained high in France, and the risk of recurrence did not depend on the etiology of the first event. Our results emphasize the importance of targeting patients with a major complication and/or an impaired LVEF who are at a higher risk of recurrence.

High dose of epinephrine does not improve survival of children with out-of-hospital cardiac arrest: Results from the French National Cardiac Arrest Registry.

Objectives: The pediatric resuscitation guidelines recommend the use of 0. 01 mg kg-1 epinephrine during a cardiac arrest; an epinephrine dose higher than that is not recommended. The first aim of this study was to determine the administration rate of high epinephrine dose during pediatric out-of-hospital cardiac arrest. The second aim was to compare the survival status in patients who received high or standard doses of epinephrine. Methods: This was a multicenter comparative post-hoc study conducted between January 2011 and July 2021 based on the French National Cardiac Arrest Registry data. All prepubescent (boys < 12 years old, girls < 10 years old) victims of an out-of-hospital cardiac arrest were included. To compare survival status and control bias, patients who received a high epinephrine dose were matched with those who received a standard epinephrine dose using propensity score matching. Results: The analysis included 755 patients; 400 (53%) received a high dose and 355 (47%) received a standard dose of epinephrine. The median dose (mg kg-1) per bolus was higher in the high-dose group than that in the standard dose group (0.04 vs. 0.01 mg kg-1, P < 0.001). Before matching, there was no between-group difference in the 30-day survival rate or survival status at hospital discharge. Matching yielded 288 pairs; there was no between-group difference in the 30-day survival rate or survival at hospital discharge (High dose, n = 5; standard dose, n = 12; Odds ratios: 2.40, 95% confidence interval: 0.85-6.81). Only 2 patients in the standard dose group had a good neurological outcome. Conclusion: More than 50% of the patients did not receive the recommended epinephrine dose during resuscitation. There was no association between patients receiving a high dose or standard dose of epinephrine with the 30-day survival or survival status at hospital discharge. Collaboration across multiple cardiac arrest registries is needed to study the application of pediatric guidelines.

Out-of-hospital cardiac arrest in pregnant women: A 55-patient French cohort study.

AIM: To describe a cohort of pregnant women having suffered an out-of-hospital cardiac arrest (OHCA) and to compare them with nonpregnant women of childbearing age having suffered OHCA. METHODS: Study data were extracted from the French National OHCA Registry between 2011 and 2021. We compared patients in terms of characteristics, care and survival. RESULTS: We included 3,645 women of childbearing age (15-44) who had suffered an OHCA; 55 of the women were pregnant. Pregnant women were younger than nonpregnant victims (30 vs. 35 years, p = 0.006) and were more likely to have a medical history (76.4% vs. 50.5%, p < 0.001) and a medical cause of the OHCA (85.5% vs. 57.2%, p < 0.001). Advanced Life Support was more frequently administered to pregnant women (98.2%, vs. 72.0%; p < 0.001). In pregnant women, the median time of MICU arrival was 20 minutes for the Medical Intensive Care Unit with no difference with nonpregnant women. Survival rate on admission to hospital was higher among pregnant women (43.6% vs. 27.3%; p = 0.009). There was no difference in 30-day survival between pregnant and nonpregnant groups (14.5% vs. 7.3%; p = 0.061). Fetal survival was only observed for OHCAs that occurred during the pregnancy second or third trimester (survival rates: 10.0% and 23.5%, respectively). CONCLUSIONS: Our results show that resuscitation performance does not meet European Resuscitation Council's specific guidelines on OHCA in pregnant women. Although OHCA in pregnancy is rare, the associated prognosis is poor for both woman and fetus. Preventive measures should be reinforced, especially when pregnant women have medical history.

Isolation and characterization of monoclonal antibodies against human carbonic anhydrase-IX.

The architectural complexity and heterogeneity of the tumor microenvironment (TME) remains a substantial obstacle in the successful treatment of cancer. Hypoxia, caused by insufficient oxygen supply, and acidosis, resulting from the expulsion of acidic metabolites, are prominent features of the TME. To mitigate the consequences of the hostile TME, cancer cells metabolically rewire themselves and express a series of specific transporters and enzymes instrumental to this adaptation. One of these proteins is carbonic anhydrase (CA)IX, a zinc-containing extracellular membrane bound enzyme that has been shown to play a critical role in the maintenance of a neutral intracellular pH (pHi), allowing tumor cells to survive and thrive in these harsh conditions. Although CAIX has been considered a promising cancer target, only two antibody-based therapeutics have been clinically tested so far. To fill this gap, we generated a series of novel monoclonal antibodies (mAbs) that specifically recognize the extracellular domain (ECD) of human CAIX. Here we describe the biophysical and functional properties of a set of antibodies against the CAIX ECD domain and their applicability as: 1) suitable for development as an antibody-drug-conjugate, 2) an inhibitor of CAIX enzyme activity, or 3) an imaging/detection antibody. The results presented here demonstrate the potential of these specific hCAIX mAbs for further development as novel cancer therapeutic and/or diagnostic tools.

Influence of motion smear on visual acuity in simulated infantile nystagmus.

PURPOSE: In persons with infantile nystagmus (IN), visual acuity correlates with the duration of the foveation period of the nystagmus waveform, i.e., when the retinal image is on or near the fovea and moves with low velocity. In this study, we asked how acuity is affected by the non-foveating phases of the nystagmus waveform, when the velocity of retinal image motion is substantially higher. METHODS: Visual acuity was measured in three normal observers for high contrast, four-orientation single T-stimuli, presented during image motion that simulated either the whole jerk-IN waveform (whole-waveform) or only the foveation periods of the IN waveform (foveation-only). Simulated foveation durations ranged from 20 to 120 ms. For both motion waveforms, we displayed the acuity target for different number of cycles to examine whether acuity benefits from multiple presentations of the stimulus. RESULTS: As expected, visual acuity improves with longer simulated foveation durations in both the whole-waveform and foveation-only conditions. Acuity is consistently better (by ∼0.1 logarithm of the minimum angle of resolution) in the foveation-only than the whole-waveform condition, indicating that the high-velocity image motion during the simulated IN waveform has a detrimental effect. This difference in acuity between the two waveform conditions increases with the number of cycles, apparently because summation occurs across cycles in the foveation-only condition but not in the whole-waveform condition. CONCLUSIONS: In normal observers, visual acuity in the presence of a simulated nystagmus waveform is limited not only by the duration of the foveation periods, but also by the non-foveating phases of the waveform. However, because persons with IN report little or no motion smear in association with their nystagmus, it remains unclear whether the rapid retinal image motion during the non-foveating phases of the nystagmus waveform generates a similar degradation of visual acuity in IN.

Multiple cytokine analysis in human tears: an optimized procedure for cytometric bead-based assay.

PURPOSE: To compare instruments and reagents used for cytometric bead-based assay (CBA) of cytokines in human tears. METHODS: Two CBA instruments and reagent kits from five vendors were compared in parallel. Vendor protocols were modified to accommodate tear volumes. Precision, recovery, dilution linearity, and stability were evaluated. RESULTS: Luminextrade mark and Bio-Radtrade mark proved optimal for tear CBA. Good correlation for dilution linearity was observed (r > 0.80, p < 0.05) for 1-4-mu l sample volumes. Samples were stable for 30 min at 25 degrees C. CONCLUSION: Many tear cytokines can be reliably measured by CBA using an optimized protocol. Concentrations remain stable during periods consistent with collection.

Thermodynamics of hydrophobic interaction chromatography of acetyl amino acid methyl esters.

Thermodynamic analysis of hydrophobic interaction chromatography of amino acid methyl esters showed entropy-driven adsorption, consistent with solvophobic theory, except for phenyl ester on the Toyopearl resins. All esters adsorbed more strongly to the Toyopearl resins, including the polymethacrylate base matrix, than to Butyl Sepharose. Enthalpy changes were more favorable with the former, explaining the retention difference between Toyopearl Butyl and Butyl Sepharose. An enthalpy change versus heat capacity change plot showed Van der Waals interactions predominantly with the resin matrix. Literature data revealed the same effect for dansylamino acids, shown by isothermodynamic temperature analysis to adsorb more entropically than the esters.

The ups and downs of peer review.

This article traces the history of peer review of scientific publications, plotting the development of the process from its inception to its present-day application. We discuss the merits of peer review and its weaknesses, both perceived and real, as well as the practicalities of several major proposed changes to the system. It is our hope that readers will gain a better appreciation of the complexities of the process and, when serving as reviewers themselves, will do so in a manner that will enhance the utility of the exercise. We also propose the development of an international on-line training program for accreditation of potential referees.