Extracorporeal cardiopulmonary resuscitation for hypothermic refractory cardiac arrests in urban areas with temperate climates.

BACKGROUND: Accidental hypothermia designates an unintentional drop in body temperature below 35 °C. There is a major risk of ventricular fibrillation below 28 °C and cardiac arrest is almost inevitable below 24 °C. In such cases, conventional cardiopulmonary resuscitation is often inefficient. In urban areas with temperate climates, characterized by mild year-round temperatures, the outcome of patients with refractory hypothermic out-of-hospital cardiac arrest (OHCA) treated with extracorporeal cardiopulmonary resuscitation (ECPR) remains uncertain. METHODS: We conducted a retrospective monocentric observational study involving patients admitted to a university hospital in Paris, France. We reviewed patients admitted between January 1, 2011 and April 30, 2022. The primary outcome was survival at 28 days with good neurological outcomes, defined as Cerebral Performance Category 1 or 2. We performed a subgroup analysis distinguishing hypothermic refractory OHCA as either asphyxic or non-asphyxic. RESULTS: A total of 36 patients were analysed, 15 of whom (42%) survived at 28 days, including 13 (36%) with good neurological outcomes. Within the asphyxic subgroup, only 1 (10%) patient survived at 28 days, with poor neurological outcomes. A low-flow time of less than 60 min was not significantly associated with good neurological outcomes (P = 0.25). Prehospital ECPR demonstrated no statistically significant difference in terms of survival with good neurological outcomes compared with inhospital ECPR (P = 0.55). Among patients treated with inhospital ECPR, the HOPE score predicted a 30% survival rate and the observed survival was 6/19 (32%). CONCLUSION: Hypothermic refractory OHCA occurred even in urban areas with temperate climates, and survival with good neurological outcomes at 28 days stood at 36% for all patients treated with ECPR. We found no survivors with good neurological outcomes at 28 days in submersed patients.

Kidneys recovered from brain dead cardiac arrest patients resuscitated with ECPR show similar one-year graft survival compared to other donors.

INTRODUCTION: Among patients treated with extracorporeal cardiopulmonary resuscitation (ECPR) as a second line of treatment for refractory out-of-hospital cardiac arrest (OHCA), some may develop brain death and become eligible for organ donation. The objective of this study was to evaluate long-term outcomes of kidney grafts recovered from these patients. MATERIAL AND METHODS: We conducted a retrospective monocentric observational study between January 1, 2011, and December 31, 2017. We exclusively included patients eligible for planned donation after brainstem death and from whom at least one organ graft was retrieved and transplanted. We compared two groups of brain dead patients: those treated with ECPR for refractory OHCA (ECPR group) and a diverse group of patients who did not receive ECPR, from which only 5/23 (22%) had OHCA (control group). The primary outcome was one-year kidney graft survival. RESULTS: We included 45 patients, 23 in the control group and 22 in the ECPR group. Although patients in the ECPR group were younger and had a lower prevalence of chronic renal disease (p = 0.01), their kidney function was more severely impaired upon admission in the ICU. A total of 68 kidney grafts were retrieved, transplanted, and studied, 34 in each study group. There was no significant difference between the two groups in terms of one-year kidney graft survival (p = 0.52). CONCLUSION: Organ transplantation from patients treated with ECPR after refractory OHCA showed one-year kidney graft survival rates comparable to those of patients not treated with ECPR.

A high-dimensional cytometry atlas of peripheral blood over the human life span.

Age can profoundly affect susceptibility to a broad range of human diseases. Children are more susceptible to some infectious diseases such as diphtheria and pertussis, while in others, such as coronavirus disease 2019 and hepatitis A, they are more protected compared with adults. One explanation is that the composition of the immune system is a major contributing factor to disease susceptibility and severity. While most studies of the human immune system have focused on adults, how the immune system changes after birth remains poorly understood. Here, using high-dimensional spectral flow cytometry and computational methods for data integration, we analyzed more than 50 populations of immune cells in the peripheral blood, generating an immune cell atlas that defines the healthy human immune system from birth up to 75 years of age. We focused our efforts on children under 18 years old, revealing major changes in immune cell populations after birth and in children of schooling age. Specifically, CD4+ T effector memory cells, Vδ2+ gamma delta (γδ)T cells, memory B cells, plasmablasts, CD11c+ B cells and CD16+ CD56bright natural killer (NK) cells peaked in children aged 5-9 years old, whereas frequencies of T helper 1, T helper 17, dendritic cells and CD16+ CD57+ CD56dim NK cells were highest in older children (10-18 years old). The frequency of mucosal-associated invariant T cells was low in the first several years of life and highest in adults between 19 and 30 years old. Late adulthood was associated with fewer mucosal-associated invariant T cells and Vδ2+ γδ T cells but with increased frequencies of memory subsets of B cells, CD4+ and CD8+ T cells and CD57+ NK cells. This human immune cell atlas provides a critical resource to understand changes to the immune system during life and provides a reference for investigating the immune system in the context of human disease. This work may also help guide future therapies that target specific populations of immune cells to protect at-risk populations.

A systematic review of geographical inequities for accessing clinical genomic and genetic services for non-cancer related rare disease.

Place plays a significant role in our health. As genetic/genomic services evolve and are increasingly seen as mainstream, especially within the field of rare disease, it is important to ensure that where one lives does not impede access to genetic/genomic services. Our aim was to identify barriers and enablers of geographical equity in accessing clinical genomic or genetic services. We undertook a systematic review searching for articles relating to geographical access to genetic/genomic services for rare disease. Searching the databases Medline, EMBASE and PubMed returned 1803 papers. Screening led to the inclusion of 20 articles for data extraction. Using inductive thematic analysis, we identified four themes (i) Current service model design, (ii) Logistical issues facing clinicians and communities, (iii) Workforce capacity and capability and iv) Rural culture and consumer beliefs. Several themes were common to both rural and urban communities. However, many themes were exacerbated for rural populations due to a lack of clinician access to/relationships with genetic specialist staff, the need to provide more generalist services and a lack of genetic/genomic knowledge and skill. Additional barriers included long standing systemic service designs that are not fit for purpose due to historically ad hoc approaches to delivery of care. There were calls for needs assessments to clarify community needs. Enablers of geographically equitable care included the uptake of new innovative models of care and a call to raise both community and clinician knowledge and awareness to demystify the clinical offer from genetics/genomics services.

Effect of High-pressure Processing on the Quality Characteristics and Shelf-life Stability of Hanwoo Beef Marinated with Various Sauces.

The effects of high-pressure processing (HPP) treatment on the quality characteristics of low graded Hanwoo beef marinated with five different sauces (soy, fish, fish-soy, soy-fish and fish-soy-meat sauces) obtained from Asian countries were studied. The Hanwoo beef striploins were marinated with the aforementioned sauces (at ratio: 3:1 w/w) for 3 days at 4℃ before they were treated with HPP at 550 MPa for 5 min at 10℃. All the sauces used were equalized to a same salt level of 12.5%, and the samples marinated with a 12.5% brine solution were served as a control. After treating with the HPP, all the samples were stored for further 7 days at 4℃ for analyses. Results revealed that HPP treatments showed some effects on technological quality traits (pH, cooking loss and color) but had no effect on the collagen contents of the marinated beef. Noticeably, the HPP treatment led to the increases in amounts of free amino acids associated with monosodium glutamate-like taste and sweet taste in the samples marinated with fish sauce or soy-fish sauce, fish-soy sauce and fish-soy-meat sauce whereas, it only reduced these amino acids in the samples marinated with soy sauce or control. Furthermore, the total bacteria count in all the marinated beef samples treated with HPP were significantly (p<0.05) lower than those of the non-HPP-treated samples throughout the storage periods. It is concluded that HPP could be applied for enhancing the taste-active compounds production such as free amino acids, and improving the shelf-life stability of the marinated beef.

Coronary lesions in refractory out of hospital cardiac arrest (OHCA) treated by extra corporeal pulmonary resuscitation (ECPR).

PURPOSE: Extracorporeal cardiopulmonary resuscitation (ECPR) is a second line treatment for refractory cardiac arrest (R-OHCA). Timing of ECPR before performing coronary angiography (CAG) is still debated. The aim of the study was to describe the clinical and angiographic characteristics of the largest cohort of out-of-hospital cardiac arrest (OHCA) patients undergoing ECPR. METHODS: All refractory OHCA patients with ECPR managed by the prehospital mobile intensive care unit (MoICU of the SAMU) in Paris (France) were prospectively included from October 2014 to December 2016. RESULTS: Among 74 patients included over the period, 54 patients had coronary artery disease (CAD). There is a trend toward the CAD patients being older but it did not meet statistical significance (55.3 ±â€¯11.8 vs. 50.6 ±â€¯12.8, p = 0,14). Patients were more frequently men and smokers (p = 0.03 for both). The proportion of initial shockable rhythm tended to be higher in patients with CAD (71% vs. 55%). The rate of 1-, 2-, and 3-vessel disease were 43%, 35% and 22% respectively. The Syntax Score was 18 ±â€¯9 and the lesions in each epicardial vessel were mainly proximal. Percutaneous coronary intervention was performed ad hoc in 49 patients (91%). Complete revascularization was performed in 64%. Inhospital death was numerically lower (65% vs. 75%) in patients with CAD, especially in patients with initial shockable rhythm. CONCLUSION: In 74 refractory OHCA patients treated with ECPR implanted by a prehospital mobile intensive care unit, the rate of CAD was high (54/74) especially in patients with shockable rhythm. The majority of patients presented with double or triple vessel disease and proximal lesions. The severity and extension of CAD may explain the refractory nature of the cardiac arrest.

Early detection of brain death using the Bispectral Index (BIS) in patients treated by extracorporeal cardiopulmonary resuscitation (E-CPR) for refractory cardiac arrest.

BACKGROUND: Despite increasing use of extracorporeal cardiopulmonary resuscitation (E-CPR) for treatment of refractory cardiac arrest patients, prognosis remains dismal, often resulting in brain-death. However, clinical assessment of brain-death occurence is difficult in post-cardiac arrest patients, sedated, paralyzed, under mild therapeutic hypothermia (MTH). Our objective was to assess the usefulness of Bispectral-Index (BIS) monitoring at bedside for an early detection of brain-death occurrence in refractory cardiac arrest patients treated by E-CPR. METHODS: This prospective study was performed in an intensive care unit of an university hospital. Forty-six patients suffering from refractory cardiac arrest treated by E-CPR were included. BIS was continuously recorded during ICU hospitalization. Clinical brain-death was confirmed when appropriate by EEG and/or cerebral CT angiography. RESULTS: Twenty-nine patients evolved into brain-death and had average BIS values under MTH and after rewarming (temperature ≥35°C) of 4 (0-47) and 0 (0-82), respectively. Among these, 11 (38%) entered into a procedure of organs donation. Among the 17 non-brain-dead patients, the average BIS values at admission and after rewarming were 39 (0-65) and 59 (22-82), respectively. Two patients had on admission a BIS value equal to zero and evolved to a poor prognostic (CPC 4) and died after care limitations. BIS values were significantly different between patients who developed brain death and those who did not. In both groups, no differences were observed between the AUCs of ROC curves for BIS values under MTH and after rewarming (respectively 0.86 vs 0.83, NS). CONCLUSIONS: Initial values of BIS could be used as an assessment tool for early detection of brain-death in refractory cardiac arrest patients treated by mild therapeutic hypothermia and E-CPR.

A Pre-Hospital Extracorporeal Cardio Pulmonary Resuscitation (ECPR) strategy for treatment of refractory out hospital cardiac arrest: An observational study and propensity analysis.

BACKGROUND: Out of hospital cardiac arrest (OHCA) mortality rates remain very high with poor neurological outcome in survivors. Extracorporeal cardiopulmonary resuscitation (ECPR) is one of the treatments of refractory OHCA. This study used data from the mobile intensive care unit (MOICU) as part of the emergency medical system of Paris, and included all consecutive patients treated with ECPR (including pre-hospital ECPR) from 2011 to 2015 for the treatment of refractory OHCA, comparing two historical ECPR management strategies. METHODS: We consecutively included refractory OHCA patients. In Period 1, ECPR was indicated in selected patients after 30min of advanced life support; in- or pre-hospital implementation depended on estimated transportation time and ECPR team availability. In Period 2, patient care relied on early ECPR initiation after 20min of resuscitation, stringent patient selection, epinephrine dose limitation and deployment of ECPR team with initial response team. Primary outcome was survival with good neurological function Cerebral Performance Category score (CPC score) 1 and 2 at ICU discharge or day 28. FINDINGS: A total of 156 patients were included. (114 in Period 1 and 42 in Period 2). Baseline characteristics were similar. Mean low-flow duration was shorter by 20min (p<0.001) in Period 2. Survival was significantly higher in Period 2: 29% vs 8% (P<0.001), as confirmed by the multivariate analysis and propensity score. When combining stringent patient selection with an aggressive strategy, the survival rate increased to 38%. Pre-hospital ECPR implementation in itself was not an independent predictor of improved survival, but it was part of the strategy in Period 2. INTERPRETATION: Our data suggest that ECPR in specific settings in the management of refractory OHCA is feasible and can lead to a significant increase in neurological intact survivors. These data, however, need to be confirmed by a large RCT.

Prehospital treatment with levetiracetam plus clonazepam or placebo plus clonazepam in status epilepticus (SAMUKeppra): a randomised, double-blind, phase 3 trial.

BACKGROUND: Generalised convulsive status epilepticus (GCSE) should be treated quickly. Benzodiazepines are the only drug treatment available so far that is effective before admission to hospital. We assessed whether addition of the antiepileptic drug levetiracetam to the benzodiazepine clonazepam would improve prehospital treatment of GCSE. METHODS: We did a prehospital, randomised, double-blind, phase 3, placebo-controlled, superiority trial to determine the efficacy of adding intravenous levetiracetam (2.5 g) to clonazepam (1 mg) in treatment of GCSE in 13 emergency medical service centres and 26 hospital departments in France. Randomisation was done at the Paris Descartes Clinical Research Unit with a list of random numbers generated by computer. Adults with convulsions lasting longer than 5 min were randomly assigned (1:1) by prehospital physicians to receive levetiracetam or placebo in combination with clonazepam. All physicians and paramedics were masked to group assignments. If the status epilepticus lasted beyond 5 min after drug injection, a second dose of 1 mg clonazepam was given. The primary outcome was cessation of convulsions within 15 min of drug injection. We analysed the modified intention-to-treat population that had received at least one injection of clonazepam and levetiracetam or placebo, excluding patients without valid consent and those randomised more than once. The trial is registered at EudraCT, number 2007-005782-35. FINDINGS: Between July 20, 2009, and Dec 15, 2012, 107 patients were randomly assigned to receive placebo and 96 were assigned to receive levetiracetam. The trial was discontinued on Dec 15, 2012 when interim analysis showed no evidence of a treatment difference, and 68 patients in each group were included in the modified intention-to-treat analysis. Convulsions stopped at 15 min of drug injection in 57 of 68 patients (84%) receiving clonazepam and placebo and in 50 of 68 patients (74%) receiving clonazepam and levetiracetam (percentage difference -10.3%, 95% CI -24.0 to 3.4). Three deaths, 19 of 47 (40 %) serious adverse events, and 90 of 197 (46%) non-serious events were reported in the levetiracetam group, and four deaths, 28 of 47 (60%) serious events, and 107 of 197 (54%) non-serious events were reported in the placebo group. INTERPRETATION: The addition of levetiracetam to clonazepam treatment presented no advantage over clonazepam treatment alone in the control of GCSE before admission to hospital. Future prehospital trials could assess the efficacy of clonazepam alone as a first-line treatment in status epilepticus and the efficacy of a second injection of clonazepam with another antiepileptic drug as second-line treatment. FUNDING: UCB Pharma.

Counterintuitive relationship between visceral fat and all-cause mortality in an elderly Asian population.

OBJECTIVE: Abdominal obesity is considered to be a risk factor for mortality. However, recent studies indicate that overweight may be negatively associated with mortality ("obesity paradox"). The relationships between mortality and various obesity markers in an elderly Asian cohort were evaluated. METHODS: Subjects of the Korean Longitudinal Study on Health and Aging (KLoSHA) (n = 1000, age ≥65 years) were included. The visceral fat area (VFA) and subcutaneous fat area (SFA) were measured using computed tomography. RESULTS: A total of 222 deaths occurred during the 6-year follow-up (median = 5.2 [range 0.1-6.3] years). Body mass index (BMI), VFA, SFA, and total fat mass were negatively associated with all-cause mortality in the univariable analyses (hazard ratio [HR] 0.67 per 1 SD [95% CI 0.57-0.77], 0.66 [0.55-0.79], 0.73 [0.61-0.86], and 0.74 [0.63-0.87], respectively). BMI and VFA were significantly associated with all-cause mortality in the multivariable analyses (HR 0.85 per 1 SD [95% CI 0.73-0.99] and 0.64 [0.47-0.87], respectively). When stratified by quartiles, the HR associated with VFA was the lowest in the third quartile. CONCLUSIONS: In this observational study with a short follow-up of elderly Asian people, higher amounts of visceral fat, a marker for central obesity, were associated with decreased all-cause mortality.

Safety and feasibility of prehospital extra corporeal life support implementation by non-surgeons for out-of-hospital refractory cardiac arrest.

BACKGROUND: Extra corporeal life support (ECLS) has been recently introduced in the treatment of refractory cardiac arrest (CA). Several studies have assessed the use of ECLS in refractory CA once the patients reach hospital. The time between CA and the implementation of ECLS is a major prognostic factor for survival. The main predictive factor for survival is ECLS access time. Pre hospital ECLS implementation could reduce access time. We therefore decided to assess the feasibility and safety of prehospital ECLS implementation (PH-ECLS) in a pilot study. METHODS AND RESULTS: From January 2011 to January 2012, PH-ECLS implementation for refractory CA was performed in 7 patients by a PH-ECLS team including emergency and/or intensivist physicians and paramedics. Patients were included prospectively and consecutively if the following criteria were met: they had a witnessed CA; CPR was initiated within the first 5 min of CA and/or there were signs of life during CPR; an PH-ECLS team was available and absence of severe comorbidities. ECLS flow was established in all patients. ECLS was started 22 min (±6) after the incision, and 57 min (±21) after the onset of advanced cardiovascular life support (ACLS). In one patient, ECLS was stopped for 10 min due to an accidental decannulation. One patient survived without sequelae. Three patients developed brain death. CONCLUSIONS: This pilot study suggests that PH-ECLS performed by non-surgeons is safe and feasible. Further studies are needed to confirm the time saved by this strategy and its potential effect on survival.

A prehospital randomized trial in convulsive status epilepticus.

Therapeutic strategies for patients with generalized convulsive status epilepticus (GCSE) need to be improved. We present the design of an add-on, randomized, double-blind, placebo-controlled, phase III clinical trial, to compare the efficacy for GCSE of intravenous levetiracetam in association with clonazepam versus clonazepam alone. In the therapeutic arm, 1 mg clonazepam is injected together with 2500 mg levetiracetam over 5 min. In the control arm, 1 mg clonazepam is injected together with a placebo over 5 min. This ongoing study is managed by prehospital physicians within emergency mobile units (SAMU). Adult patients with GCSE lasting more than 5 minutes are included in the study. The primary outcome measure is the percentage of patients with cessation of convulsions within 15 minutes of the onset of initial injections. Emergency medical consent is obtained from family members. An informed consent for continued participation is also obtained from patients when they wake. The study is currently recruiting participants.