The likelihood of neurological recovery after out-of-hospital cardiac arrest (OHCA) may be influenced by advanced age. This study aims to evaluate the impact of advanced age on neurological recovery in elderly OHCA survivors treated with targeted temperature management (TTM). This retrospective observational study, using a nationwide population-based OHCA registry, was conducted from January 2016 to December 2020. Non-traumatic elderly (≥ 65 years) comatose OHCA survivors treated with TTM were categorized according to age (65-69, 70-74, 75-79, and ≥ 80 years). Among 23,336 admitted OHCA patients, 3,398 were treated with TTM. Excluding 2,033 non-elderly patients, 1,365 were analyzed. Among the four groups, the rate of good neurological outcomes decreased by advanced age (24.2%, 16.1%, 11.4%, and 5.9%, respectively), which was also observed after subgroup analysis based on the initial shockable (40.6%, 31.5%, 28.6%, and 14.9%, respectively) and non-shockable rhythm (10.6%, 7.2%, 4.1%, and 3.4%, respectively). Multivariate analysis showed the adjusted odds ratio (aOR) for good neurological outcome decreased as age increased (65-69: reference, 70-74: aOR 0.70, 75-79: aOR 0.49, and ≥ 80 years: aOR 0.25). The optimal age cutoffs for good outcomes in elderly OHCA survivors with shockable and non-shockable rhythm were 77 and 72 years, respectively. The neurologic recovery rate in OHCA survivors treated with TTM gradually decreased with increasing age. However, even patients aged ≥ 80 years with shockable rhythm had a good neurologic outcome of 14.9% compared with patients aged 65-69 years with non-shockable rhythm (10.6%).

Delayed hypothermia, initiated after hospital arrival, several hours after cardiac arrest with 8-10 hours to reach the target temperature, is likely to have limited impact on overall survival. However, the effect of ultrafast hypothermia, i.e., delivered intra-arrest or immediately after return of spontaneous circulation (ROSC), on functional neurologic outcome after out-of-hospital cardiac arrest (OHCA) is unclear. In two prior trials, prehospital trans-nasal evaporative intra-arrest cooling was safe, feasible and reduced time to target temperature compared to delayed cooling. Both studies showed trends towards improved neurologic recovery in patients with shockable rhythms. The aim of the PRINCESS2-study is to assess whether cooling, initiated either intra-arrest or immediately after ROSC, followed by in-hospital hypothermia, significantly increases survival with complete neurologic recovery as compared to standard normothermia care, in OHCA patients with shockable rhythms.
In this investigator-initiated, randomized, controlled trial, the emergency medical services (EMS) will randomize patients at the scene of cardiac arrest to either trans-nasal cooling within 20 minutes from EMS arrival with subsequent hypothermia at 33°C for 24 hours after hospital admission (intervention), or to standard of care with no prehospital or in-hospital cooling (control). Fever (>37,7°C) will be avoided for the first 72 hours in both groups. All patients will receive post resuscitation care and withdrawal of life support procedures according to current guidelines. Primary outcome is survival with complete neurologic recovery at 90 days, defined as modified Rankin scale (mRS) 0-1. Key secondary outcomes include survival to hospital discharge, survival at 90 days and mRS 0-3 at 90 days. In total, 1022 patients are required to detect an absolute difference of 9% (from 45 to 54%) in survival with neurologic recovery (80% power and one-sided α=0,025, β=0,2) and assuming 2,5% lost to follow-up. Recruitment starts in Q1 2024 and we expect maximum enrolment to be achieved during Q4 2024 at 20-25 European and US sites.
This trial will assess the impact of ultrafast hypothermia applied on the scene of cardiac arrest, as compared to normothermia, on 90-day survival with complete neurologic recovery in OHCA patients with initial shockable rhythm.
NCT06025123.

This study aims to evaluate whether neuron-specific enolase (NSE) level at 48 h after extracorporeal cardiopulmonary resuscitation (ECPR) is associated with neurologic outcomes at 6 months after hospital discharge.
This was a retrospective, multicenter, observational study of adult patients who received ECPR between May 2010 and December 2016. In the two hospitals involved in this study, NSE measurements were a routine part of the protocol for patients who received ECPR. Serial NSE levels were measured in all patients with ECPR. NSE levels were measured 24, 48, and 72 h after ECPR. The primary outcome was Cerebral Performance Categories (CPC) scale at 6 months after hospital discharge according to NSE levels at 48 h after ECPR.
At follow-up 6 months after hospital discharge, favorable neurologic outcomes of CPC 1 or 2 were observed in 9 (36.0%) of the 25 patients, and poor neurologic outcomes of CPC 3, 4, or 5 were observed in 16 (64%) patients. NSE levels at 24 h in the favorable and poor neurologic outcome groups were 58.3 (52.5-73.2) μg/L and 64.2 (37.9-89.8) μg/L, respectively (p = 0.95). NSE levels at 48 h in the favorable and poor neurologic outcome groups were 52.1 (22.3-64.9) μg/L and 302.0 (62.8-360.2) μg/L, respectively (p = 0.01). NSE levels at 72 h were 37.2 (12.5-53.2) μg/L and 240.9 (75.3-370.0) μg/L, respectively (p < 0.01). In receiver operating characteristic (ROC) curve analysis, as the predictor of poor outcome, the optimal cut-off value for NSE level at 48 h was 140.5 μg/L, and the area under the curve (AUC) was 0.844 (p < 0.01). The optimal cut-off NSE level at 72 h was 53.2 μg/L, and the AUC was 0.897 (p < 0.01).
NSE level at 72 h displayed the highest association with neurologic outcome after ECPR, and NSE level at 48 h was also associated with neurologic outcome after ECPR.

The effect of COVID-19 in pregnancy on maternal outcomes and its association with preeclampsia and gestational diabetes mellitus have been reported; however, a detailed understanding of the effects of maternal positivity, delivery mode, and perinatal practices on fetal and neonatal outcomes is urgently needed.
To evaluate the impact of COVID-19 on fetal and neonatal outcomes and the role of mode of delivery, breastfeeding, and early neonatal care practices on the risk of mother-to-child transmission.
In this cohort study that took place from March 2020 to March 2021, involving 43 institutions in 18 countries, 2 unmatched, consecutive, unexposed women were concomitantly enrolled immediately after each infected woman was identified, at any stage of pregnancy or delivery, and at the same level of care to minimize bias. Women and neonates were followed up until hospital discharge. COVID-19 in pregnancy was determined by laboratory confirmation and/or radiological pulmonary findings or ≥2 predefined COVID-19 symptoms. The outcome measures were indices of neonatal and perinatal morbidity and mortality, neonatal positivity and its correlation with mode of delivery, breastfeeding, and hospital neonatal care practices.
A total of 586 neonates born to women with COVID-19 diagnosis and 1535 neonates born to women without COVID-19 diagnosis were enrolled. Women with COVID-19 diagnosis had a higher rate of cesarean delivery (52.8% vs 38.5% for those without COVID-19 diagnosis, P<.01) and pregnancy-related complications, such as hypertensive disorders of pregnancy and fetal distress (all with P<.001), than women without COVID-19 diagnosis. Maternal diagnosis of COVID-19 carried an increased rate of preterm birth (P≤.001) and lower neonatal weight (P≤.001), length, and head circumference at birth. In mothers with COVID-19 diagnosis, the length of in utero exposure was significantly correlated to the risk of the neonate testing positive (odds ratio, 4.5; 95% confidence interval, 2.2-9.4 for length of in utero exposure >14 days). Among neonates born to mothers with COVID-19 diagnosis, birth via cesarean delivery was a risk factor for testing positive for COVID-19 (odds ratio, 2.4; 95% confidence interval, 1.2-4.7), even when severity of maternal conditions was considered and after multivariable logistic analysis. In the subgroup of neonates born to women with COVID-19 diagnosis, the outcomes worsened when the neonate also tested positive, with higher rates of neonatal intensive care unit admission, fever, gastrointestinal and respiratory symptoms, and death, even after adjusting for prematurity. Breastfeeding by mothers with COVID-19 diagnosis and hospital neonatal care practices, including immediate skin-to-skin contact and rooming-in, were not associated with an increased risk of newborn positivity.
In this multinational cohort study, COVID-19 in pregnancy was associated with increased maternal and neonatal complications. Cesarean delivery was significantly associated with newborn COVID-19 diagnosis. Vaginal delivery should be considered the safest mode of delivery if obstetrical and health conditions allow it. Mother-to-child skin-to-skin contact, rooming-in, and direct breastfeeding were not risk factors for newborn COVID-19 diagnosis, thus well-established best practices can be continued among women with COVID-19 diagnosis.

This study investigated the patient outcomes, incidence, and predisposing factors of elevated pancreatic enzyme levels after OHCA. We conducted a retrospective cohort study of patients treated with targeted temperature management (TTM) after out-of-hospital cardiac arrest (OHCA). Elevation of pancreatic enzyme levels was defined as serum amylase or lipase levels that were at least three times the upper limit of normal. The factors associated with elevated pancreatic enzyme levels and their association with neurologic outcomes and mortality 28 days after OHCA were analyzed. Among the 355 patients, 166 (46.8%) patients developed elevated pancreatic enzyme levels. In the multivariable analysis (odds ratio, 95% confidence interval), initial shockable rhythm (0.62, 0.39−0.98, p = 0.04), time from collapse to return of spontaneous circulation (1.02, 1.01−1.04, p < 0.001), and history of coronary artery disease (1.7, 1.01−2.87, p = 0.046) were associated with elevated pancreatic enzyme levels. After adjusting for confounding factors, elevated pancreatic enzyme levels were associated with neurologic outcomes (5.44, 3.35−8.83, p < 0.001) and mortality (3.74, 2.39−5.86, p < 0.001). Increased pancreatic enzyme levels are common in patients treated with TTM after OHCA and are associated with unfavorable neurologic outcomes and mortality at 28 days after OHCA.

BACKGROUND: We assessed the prognostic accuracy of the standardized electroencephalography (EEG) patterns (\"highly malignant,\" \"malignant,\" and \"benign\") according to the EEG timing (early vs. late) and investigated the EEG features to enhance the predictive power for poor neurologic outcome at 1 month after cardiac arrest.
METHODS: This prospective, multicenter, observational, cohort study using data from Korean Hypothermia Network prospective registry included adult patients with out-of-hospital cardiac arrest (OHCA) treated with targeted temperature management (TTM) and underwent standard EEG within 7 days after cardiac arrest from 14 university-affiliated teaching hospitals in South Korea between October 2015 and December 2018. Early EEG was defined as EEG performed within 72 h after cardiac arrest. The primary outcome was poor neurological outcome (Cerebral Performance Category score 3-5) at 1 month.
RESULTS: Among 489 comatose OHCA survivors with a median EEG time of 46.6 h, the \"highly malignant\" pattern (40.7%) was most prevalent, followed by the \"benign\" (33.9%) and \"malignant\" (25.4%) patterns. All patients with the highly malignant EEG pattern had poor neurologic outcomes, with 100% specificity in both groups but 59.3% and 56.1% sensitivity in the early and late EEG groups, respectively. However, for patients with \"malignant\" patterns, 84.8% sensitivity, 77.0% specificity, and 89.5% positive predictive value for poor neurologic outcome were observed. Only 3.5% (9/256) of patients with background EEG frequency of predominant delta waves or undetermined had good neurologic survival. The combination of \"highly malignant\" or \"malignant\" EEG pattern with background frequency of delta waves or undetermined increased specificity and positive predictive value, respectively, to up to 98.0% and 98.7%.
CONCLUSIONS: The \"highly malignant\" patterns predicted poor neurologic outcome with a high specificity regardless of EEG measurement time. The assessment of predominant background frequency in addition to EEG patterns can increase the prognostic value of OHCA survivors. Trial registration KORHN-PRO, NCT02827422 . Registered 11 September 2016-Retrospectively registered.

We aimed to characterize extracorporeal CPR (ECPR) outcomes in our center and to model prediction of severe functional impairment or death at discharge.
All ECPR events between 2011 and 2019 were reviewed. The primary outcome measure was severe functional impairment or death at discharge (Functional Status Score [FSS] ≥ 16). Organ dysfunction was graded using the Pediatric Logistic Organ Dysfunction Score-2, neuroimaging using the modified Alberta Stroke Program Early Computed Tomography Score. Multivariable logistic regression was used to model FSS ≥ 16 at discharge.
Of the 214 patients who underwent ECPR, 182 (median age 148 days, IQR 14-827) had an in-hospital cardiac arrest and congenital heart disease and were included in the analysis. Of the 110 patients who underwent neuroimaging, 52 (47%) had hypoxic-ischemic injury and 45 (41%) had hemorrhage. In-hospital mortality was 52% at discharge. Of these, 87% died from the withdrawal of life-sustaining therapies; severe neurologic injury was a contributing factor in the decision to withdraw life-sustaining therapies in 50%. The median FSS among survivors was 8 (IQR 6-8), and only one survivor had severe functional impairment. At 6 months, mortality was 57%, and the median FSS among survivors was 6 (IQR 6-8, n = 79). Predictive models identified FSS at admission, single ventricle physiology, extracorporeal membrane oxygenation (ECMO) duration, mean PELOD-2, and worst mASPECTS (or DWI-ASPECTS) as independent predictors of FSS ≥ 16 (AUC = 0.931) and at 6 months (AUC = 0.924).
Mortality and functional impairment following ECPR in children remain high. It is possible to model severe functional impairment or death at discharge with high accuracy using daily post-ECPR data up to 28 days. This represents a prognostically valuable tool and may identify endpoints for future interventional trials.

Clamping of the thoracoabdominal aorta reduces perfusion of the spinal cord significantly, which clinically may present as paraparesis or paraplegia – devastating and unpredictable complications of open thoracoabdominal aortic surgery. Introduction of monitoring of evoked potentials and/or biochemical markers, methods increasing distal arterial pressure, indirect procedures enhancing residual flow (like liquor drainage), drugs, and use of hypothermia contributed to achieve better outcome. Preconditioning of spinal cord circulation is also a promising method. New endovascular techniques for thoracoabdominal aortic aneurysms and dissections reduced surgical trauma significantly. Despite all these progressions spinal cord ischemic damage is still a significant risk. To address this problem we carried out an experimental work using a canine model focusing on the protective effect of distal arterial perfusion, spinal fluid drainage, and their combination in a one hour setting of thoracoabdominal aortic clamping. In this paper we publish our data of circulatory and specific perfusion parameters of the spinal cord during and after declamping in correlation of final neurologic outcome.
Összefoglaló. A thoracoabdominalis aorta kirekesztése a gerincvelő keringésének csökkenését okozza. Az ischemia klinikailag paraparesis, paraplegia formájában jelenik meg. Ez elsősorban nyitott műtétek során jelent aligha kiszámítható szövődményt, de a modern endovascularis technikák sem oldották meg teljes mértékben ennek biztonságos kivédését – bár arányát jelentősen mérsékelték. A javuló eredmények számos tényezőre vezethetők vissza, mint a keringés kirekesztési idejének csökkentése, a gerincvelő-funkció és metabolismus ellenőrzése. Mesterséges keringésjavító direkt és indirekt eljárások, liquor drainage, hűtés mellett a collateralis keringés javítását szolgáló prekondicionáló módszerek kerültek bevezetésre. Kísérletes munkánkban 25–30 kg testsúlyú kutyákon vizsgáltuk – más paraméterek mellett – a distalis perfusio növelésének, a liquornyomás csökkentésének, illetve ezek kombinációjának protektív hatását egyórás thoracoabdominalis aortakirekesztés során. Dolgozatunkban a kísérleti állataink neurológiai végállapotát a keringési paraméterek és szöveti perfusio és a reperfusio változásainak összefüggésein keresztül tárgyaljuk. Megállapítottuk, hogy distalis gerincvelő reperfusiós hyperaemiája szorosan összefügg a neurológiai károsodás mértékével.

Conventional MRI measures of traumatic spinal cord injury severity largely rely on 2-dimensional injury characteristics such as intramedullary lesion length and cord compression. Recent advances in spinal cord (SC) analysis have led to the development of a robust anatomic atlas incorporated into an open-source platform called the Spinal Cord Toolbox (SCT) that allows for quantitative volumetric injury analysis. In the current study, we evaluate the prognostic value of volumetric measures of spinal cord injury on MRI following registration of T2-weighted (T2w) images and segmented lesions from acute SCI patients with a standardized atlas. This IRB-approved prospective cohort study involved the image analysis of 60 blunt cervical SCI patients enrolled in the TRACK-SCI clinical research protocol. Axial T2w MRI data obtained within 24 h of injury were processed using the SCT. Briefly, SC MRIs were automatically segmented using the sct_deepseg_sc tool in the SCT and segmentations were manually corrected by a neuro-radiologist. Lesion volume data were used as predictor variables for correlation with lower extremity motor scores at discharge. Volumetric MRI measures of T2w signal abnormality comprising the SCI lesion accurately predict lower extremity motor scores at time of patient discharge. Similarly, MRI measures of injury volume significantly correlated with motor scores to a greater degree than conventional 2-D metrics of lesion size. The volume of total injury and of injured spinal cord motor regions on T2w MRI is significantly and independently associated with neurologic outcome at discharge after injury.

Subarachnoid hemorrhage (SAH) is associated with high morbidity. Among all complications, infections, in particular if hospital acquired, could represent an important cause of death in patients with SAH. The aim of this study was to describe infectious complications in patients with SAH and to evaluate their impact on outcome.
A single-center cohort study included all patients with SAH admitted from January 2011 to December 2016, who stayed in the intensive care unit for at least 24 hours. Infection diagnosis was retrieved from medical files; central nervous system infections were not included. A multivariable analysis was performed to identify risk factors for development of infection. Logistic regression was performed to identify risks for unfavorable neurologic outcome at 3 months, defined as a Glasgow Outcome Scale score of 1-3.
Of the 248 patients with SAH, 70 (28.2%) developed at least 1 infection; the most frequent site of infection was respiratory (57.1%), primary bloodstream (16%), and urinary tract infections (15.7%). Twenty-eight patients (11.3% of all patients) had at least 1 episode of septic shock. Infected patients had a higher unfavorable outcome rate (60.0% vs. 33.3%; P = 0.001). Diabetes mellitus (subdistribution hazard ratio, 1.79; 95% confidence interval [CI], 1.03-3.13) and intracranial hypertension (subdistribution hazard ratio, 1.92; 95% CI, 1.14-3.25) were independently associated with the occurrence of infections. Septic shock (odds ratio, 6.36; 95% CI, 1.24-32.51; P = 0.02) was independently associated with unfavorable outcome.
Infections in patients with SAH are prevalent, especially pneumonia. Septic shock is associated with a poor neurologic outcome in this group of patients.