Marjaana Tiainen

Background: Acute kidney injury (AKI) is a common and serious complication after cardiac arrest, affecting more than 30% of initially successfully resuscitated patients, with around 10% receiving Kidney Replacement Therapy (KRT). Currently, treatment options to prevent renal complications are limited. In this predefined sub‐study of the Sedation, TEmperature and Pressure after Cardiac Arrest and REsuscitation (STEPCARE) trial, we evaluate the effects of sedation depth, fever management strategies, and mean arterial pressure (MAP) targets on the risk of major adverse kidney events (MAKE) in post‐cardiac arrest patients. Methods: STEPCARE‐MAKE is a predefined prospective sub‐study of the international, randomized clinical STEPCARE trial. The main trial will enroll 3500 patients and employs a 2 × 2 × 2 factorial design, randomizing participants across three interventions: (1) deep sedation for 36 h or minimal sedation, (2) fever management with or without a feedback‐controlled device, and (3) MAP target ≥ 65 mmHg or ≥ 85 mmHg. The primary outcome is the composite outcome MAKE, which includes death from any cause by day 30, initiation of KRT, or persistent renal dysfunction, defined as the final creatinine value ≥ 200% of the baseline at the time of discharge from the primary hospital or at day 30, whichever occurs first. Differences between baseline and the highest in‐hospital creatinine, baseline and the last measured in‐hospital creatinine, baseline and 72‐h creatinine, and baseline and the highest creatinine within 72 h will be reported as secondary outcomes. Conclusion: The findings of this sub‐study will provide new evidence on the renal effects of the STEPCARE trial interventions and may inform the future of individualized kidney‐protective treatment approaches.

Introduction After resuscitation from out of hospital cardiac arrest (OHCA), mechanical ventilation (MV) and respiratory management are fundamental to support patients in the intensive care unit (ICU) and to minimise secondary brain injury. Best practices for MV and association with clinical outcomes in patients with OHCA remain unclear. Methods and analysis This protocol describes a pre-planned respiratory-focused series of sub-analyses within the Sedation, Temperature and Pressure after Cardiac Arrest and Resuscitation (STEPCARE) trial, an ongoing interventional study evaluating 6-month mortality after randomisation in patients admitted to ICUs following OHCA. The primary aim is to describe real-world ventilator settings and gas-exchange targets during the first 72 hours after ICU admission in patients receiving invasive mechanical ventilation after OHCA. Secondary aims include to estimate the incidence of respiratory complications during ICU stay (eg, ventilator-associated pneumonia, acute respiratory distress syndrome, barotrauma); and to explore the association between early ventilator settings/gas-exchange parameters and 6-month outcomes (mortality and neurological status). Exploratory aim is to characterise weaning and extubation practices, including timing and failure rates. Eligible patients will include adult STEPCARE participants receiving invasive MV after return of spontaneous circulation with available respiratory data recorded within the STEPCARE database. Data collected in the STEPCARE trial that will be analysed include patients’ prehospital characteristics; clinical examination at hospital admission and at ICU admission; ventilator settings and arterial blood gases recorded at predefined time points during ICU stay. In particular: MV setting (mode, tidal volume, positive end-expiratory pressure, fraction of inspired oxygen, tidal volume, mechanical power, plateau/driving pressures), gas-exchange values (arterial partial pressure of oxygen and carbon dioxide, pH, arterial saturation of oxygen), timing of measurements and the occurrence/timing of respiratory complications and weaning outcomes. Ethics and dissemination The STEPCARE study has been approved by the regional ethics committee at Lund University (Dnr 2022-02425-01, Approved IRB on 2022-06-18) and by all ethics boards in the participating countries. No additional ethical approval is required for this predefined secondary analysis, as no further data collection or interventions will be performed. Findings will be disseminated through publication in peer-reviewed journals and, where appropriate, conference abstracts and presentations. Patients and the public were not involved. ClinicalTrials.gov NCT05564754.

Background: Cognitive impairment in intensive care unit (ICU) survivors is multifactorial and can affect especially memory, attention, and executive functions. This study aimed to determine the cognitive functioning of patients with circulatory shock immediately after ICU discharge and 3 months later. Methods: This study, ASSESS‐SHOCK 2, is a preplanned sub‐study of the observational ASSESS‐SHOCK study conducted at Helsinki University Hospital ICU. We included adults with circulatory shock, defined as hypotension requiring vasopressor infusion and concomitant signs of hypoperfusion. We excluded patients with severe neurological or psychiatric diagnoses, impairment of hearing or vision, developmental disability, and language barriers. Cognitive functioning of patients was assessed within 3 days of ICU discharge and 3 months thereafter with the Montreal Cognitive Assessment (MoCA) test. We defined cognitive impairment as MoCA score < 26 points. We also included data of 48 volunteer controls, tested once, to analyses. Results: Fifty‐five patients underwent an assessment within 3 days of ICU discharge, and 36 of them completed a follow‐up assessment at 3 months. At discharge median MoCA‐score was 22 (IQR 17–25). At the 3 months follow‐up, the median MoCA‐score was 26.5 points (IQR 24.25–28) showing improvement from discharge to follow‐up ( p < 0.001). The prevalence of cognitive impairment at discharge was 78.2%, and, at the 3‐month follow‐up 44.4%. In the control group, the median MoCA score was 27 points (IQR 25–28) and the prevalence of cognitive impairment 33%. Conclusion: We found cognitive impairment in more than three out of four ICU survivors immediately after ICU treatment for circulatory shock. We observed an improvement in cognitive functioning between ICU discharge and 3 months follow‐up. These results have importance considering the optimal timing of information given to patients and when involving patients in decision‐making. Editorial Comment: This study used the MoCA score to investigate the change in cognitive impairment in patients who survived circulatory shock, from the time of discharge from intensive care to 3 months after discharge. Scores indicated more severe cognitive dysfunction compared to controls at the time of discharge, but these improved to match control scores 3 months later. The findings have important implications for strategies to inform and support newly discharged ICU survivors who have experienced circulatory shock.

Background: Guidelines discourage prediction of neurological outcome in comatose patients within the first 72 h after cardiac arrest. Increasing evidence suggests that patients with the most severe brain injury and those with no or minimal brain injury may be identified before 72 h using novel methods. We present a protocol for the EARLY‐NEURO study, which aims to evaluate whether good and poor outcomes can be reliably predicted already from 24 h after cardiac arrest using the most commonly available methods. Methods: Protocol for a prospective international multicenter substudy within the Sedation, TEmperature and Pressure after Cardiac Arrest and REsuscitation (STEPCARE) trial where adults post‐arrest are randomized to minimal or deep sedation, fever treatment with or without a temperature management device and to two different targets of mean arterial blood pressure. Patients sedated or still unconscious at 24 h are examined with head computed tomography (CT) and electroencephalogram (EEG). Blood samples are collected at 24 h after randomization, and stored for analysis of the brain injury marker neurofilament light. CT and EEG examinations will be centrally evaluated for signs of a likely poor or good outcome applying standardized criteria by raters blinded to treatment allocations and patient outcomes. Intensive care treatment, neurological prognostication, and criteria for withdrawal of care will be according to the STEPCARE protocol. Timepoint and reasons for withdrawal of life‐sustaining therapy (WLST) will be recorded. WLST prior to 72 h after randomization based on a presumed futile neurological prognosis is strongly discouraged. Primary outcome will be good or poor functional outcome, assessed by the modified Rankin Scale (dichotomized as 0–3 versus 4–6) at 6 months. Results will be reported in accordance with the Standards for Reporting Diagnostic Accuracy (STARD). Conclusions: Earlier prognostication aims to balance the avoidance of premature treatment withdrawal in patients with favorable potential against the prevention of unnecessary intervention in patients with a definitely poor prognosis.

Background and aims: Previous observational data indicate that young adults treated with intravenous thrombolysis (IVT) for acute ischemic stroke have more favorable outcomes and less complications when compared to older adults. Given the limited data on this topic, we aimed to provide more evidence on clinical outcomes and safety in such patients, using a large international thrombolysis registry. Methods: In this prospective multicenter study, we used data from the Thrombolysis in Ischemic Stroke Patients (TRISP) registry from 1998 to 2020. Patients who received endovascular treatment (EVT), as only treatment or in addition to IVT, were not included in this cohort. Using multivariable regression models, we compared thrombolysed young patients aged 18–49 years with those aged ⩾50 years with regards to the following outcomes: favorable outcome in stroke survivors (modified Rankin Scale ⩽2), symptomatic intracranial hemorrhage (sICH) according to European Cooperative Acute Stroke Study II (ECASS II) criteria, and three-months all-cause death. Results: Of the 16,651 IVT treated patients, 1346 (8.1%) were 18–49 years. Young adults in TRISP were more often male (59.6% vs 54.0%), had a lower median NIHSS score on admission, 7 (4–13) versus 8 (5–15), and had less cardiovascular risk factors except for smoking (42.0% vs 19.0%) when compared to older patients. When compared to thrombolysed patients aged ⩾50 years, a favorable functional outcome was more likely in young adults: 81.9% versus 56.4%, aOR 2.30 (1.80–2.95), whilst sICH 1.6% versus 4.6%, aOR 0.45 (0.23–0.90) and death 2.3% versus 14.2%, aOR 0.21 (0.11–0.39) were less likely. Conclusions: Intravenous thrombolysis in young adults is independently associated with higher rates of favorable outcomes and lower rates of complications.

Cognitive impairment in patients with COVID-19 has been reported, but findings are inconsistent. This study assessed cognitive functioning 6 months post-infection across three COVID-19 severity groups compared to non-COVID controls. Seventy-two ICU-treated, 49 ward-treated, and 44 home-isolated patients with COVID-19, along with 48 controls, underwent neuropsychological evaluation and assessment of subjective cognitive symptoms, depressive symptoms, and fatigue. Cognitive test scores were compared using ANCOVA. Associations between cognitive functioning and variables including demographics, illness severity, comorbidities, depressive symptoms, fatigue, and ICU-related factors were examined with hierarchical linear regression models. Results showed no significant differences in cognitive test performance of impairment frequencies between COVID-19 groups and controls. However, patients with COVID-19 reported higher levels of subjective cognitive symptoms, depressive symptoms, and fatigue compared to controls. Predictors of cognitive functioning included age, education, and, to a lesser extent, comorbidities. COVID-19 severity, depression, fatigue, or ICU-related variables did not significantly impact performance. These findings suggest that while individual cognitive impairments may exist, overall cognitive functioning in patients with COVID-19 was comparable to controls.

BACKGROUND: Hyperglycemia in acute ischemic stroke reduces the efficacy of stroke thrombolysis and thrombectomy, with worse clinical outcomes. Insulin-based therapies are difficult to implement and may cause hypoglycemia. We investigated whether exenatide, a GLP-1 (glucagon-like peptide-1) receptor agonist, would improve stroke outcomes, and control poststroke hyperglycemia with minimal hypoglycemia. METHODS: The TEXAIS trial (Treatment With Exenatide in Acute Ischemic Stroke) was an international, multicenter, phase 2 prospective randomized clinical trial (PROBE [Prospective Randomized Open Blinded End-Point] design) enrolling adult patients with acute ischemic stroke ≤9 hours of stroke onset to receive exenatide (5 µg BID subcutaneous injection) or standard care for 5 days, or until hospital discharge (whichever sooner). The primary outcome (intention to treat) was the proportion of patients with ≥8-point improvement in National Institutes of Health Stroke Scale score (or National Institutes of Health Stroke Scale scores 0–1) at 7 days poststroke. Safety outcomes included death, episodes of hyperglycemia, hypoglycemia, and adverse event. RESULTS: From April 2016 to June 2021, 350 patients were randomized (exenatide, n=177, standard care, n=173). Median age, 71 years (interquartile range, 62–79), median National Institutes of Health Stroke Scale score, 4 (interquartile range, 2–8). Planned recruitment (n=528) was stopped early due to COVID-19 disruptions and funding constraints. The primary outcome was achieved in 97 of 171 (56.7%) in the standard care group versus 104 of 170 (61.2%) in the exenatide group (adjusted odds ratio, 1.22 [95% CI, 0.79–1.88]; P=0.38). No differences in secondary outcomes were observed. The per-patient mean daily frequency of hyperglycemia was significantly less in the exenatide group across all quartiles. No episodes of hypoglycemia were recorded over the treatment period. Adverse events of mild nausea and vomiting occurred in 6 (3.5%) exenatide patients versus 0 (0%) standard care with no withdrawal. CONCLUSIONS: Treatment with exenatide did not reduce neurological impairment at 7 days in patients with acute ischemic stroke. Exenatide did significantly reduce the frequency of hyperglycemic events, without hypoglycemia, and was safe to use. Larger acute stroke trials using GLP-1 agonists such as exenatide should be considered. REGISTRATION: URL: www.australianclinicaltrials.gov.au; Unique identifier: ACTRN12617000409370. URL: https://www.clinicaltrials.gov; Unique identifier: NCT03287076.

Introduction: Computed tomography perfusion (CTP) imaging has become an important tool in evaluating acute recanalization treatment candidates. Large clinical trials have successfully used RAPID automated imaging analysis software for quantifying ischemic core and penumbra, yet other commercially available software vendors are also on the market. We evaluated the possible difference in ischemic core and perfusion lesion volumes and the agreement rate of target mismatch between OLEA, MIStar, and Syngo.Via versus RAPID software in acute recanalization treatment candidates. Patients and methods: All consecutive stroke-code patients with baseline CTP RAPID imaging at Helsinki University Hospital during 8/2018–9/2021 were included. Ischemic core was defined as cerebral blood flow 3s with MIStar. Perfusion lesion volume was defined as DT > 3 s (MIStar) and Tmax > 6 s with all other software. A perfusion mismatch ratio of ⩾1.8, a perfusion lesion volume of ⩾15 mL, and ischemic core <70 mL was defined as target mismatch. The mean pairwise differences of the core and perfusion lesion volumes between software were calculated using the Bland-Altman method and the agreement of target mismatch between software using the Pearson correlation. Results: A total of 1606 patients had RAPID perfusion maps, 1222 of which had MIStar, 596 patients had OLEA, and 349 patients had Syngo.Via perfusion maps available. Each software was compared with simultaneously analyzed RAPID software. MIStar showed the smallest core difference compared with RAPID (−2 mL, confidence interval (CI) from −26 to 22), followed by OLEA (2 mL, CI from −33 to 38). Perfusion lesion volume differed least with MIStar (4 mL, CI from −62 to 71) in comparison with RAPID, followed by Syngo.Via (6 mL, CI from −94 to 106). MIStar had the best agreement rate with target mismatch of RAPID followed by OLEA and Syngo.Via. Discussion and conclusion: Comparison of RAPID with three other automated imaging analysis software showed variance in ischemic core and perfusion lesion volumes and in target mismatch.