| 1. |
- Andersson, Axel, et al.
(author)
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In-hospital versus out-of-hospital cardiac arrest : Characteristics and outcomes in patients admitted to intensive care after return of spontaneous circulation
- 2022
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In: Resuscitation. - : Elsevier BV. - 0300-9572. ; 176, s. 1-8
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Journal article (peer-reviewed)abstract
- Introduction: Cardiac arrest is characterized depending on location as in-hospital cardiac arrest (IHCA) or out-of-hospital cardiac arrest (OHCA). Strategies for Post Cardiac Arrest Care were developed based on evidence from OHCA. The aim of this study was to compare characteristics and outcomes in patients admitted to intensive care after IHCA and OHCA. Methods: A retrospective multicenter observational study of adult survivors of cardiac arrest admitted to intensive care in southern Sweden between 2014–2018. Data was collected from registries and medical notes. The primary outcome was neurological outcome according to the Cerebral Performance Category (CPC) scale at 2–6 months. Results: 799 patients were included, 245 IHCA and 554 OHCA. IHCA patients were older, less frequently male and less frequently without comorbidity. In IHCA the first recorded rhythm was more often non-shockable, all delay-times (ROSC, no-flow, low-flow, time to advanced life support) were shorter and a cardiac cause of the arrest was less common. Good long-term neurological outcome was more common after IHCA than OHCA. In multivariable analysis, witnessed arrest, age, shorter arrest duration (no-flow and low-flow times), low lactate, shockable rhythm, and a cardiac cause were all independent predictors of good long-term neurological outcome whereas location of arrest (IHCA vs OHCA) was not. Conclusion: In patients admitted to intensive care after cardiac arrest, patients who suffered IHCA vs OHCA differed in demographics, co-morbidities, cardiac arrest characteristics and outcomes. In multivariable analyses, cardiac arrest characteristics were independent predictors of outcome, whereas location of arrest (IHCA vs OHCA) was not.
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| 2. |
- Arctaedius, Isabelle, et al.
(author)
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2021 European Resuscitation Council/ European Society of Intensive Care Medicine Algorithm for Prognostication of Poor Neurological Outcome After Cardiac Arrest—Can Entry Criteria Be Broadened?
- 2024
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In: Critical Care Medicine. - 0090-3493. ; 52:4, s. 531-541
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Journal article (peer-reviewed)abstract
- OBJECTIVES: To explore broadened entry criteria of the 2021 European Resuscitation Council/European Society of Intensive Care Medicine (ERC/ ESICM) algorithm for neuroprognostication including patients with ongoing sedation and Glasgow Coma Scale-Motor score (GCS-M) scores 4–5. DESIGN: Retrospective multicenter observational study. SETTING: Four ICUs, Skane, Sweden. PATIENTS: Postcardiac arrest patients managed at targeted temperature 36°C, 2014–2018. Neurologic outcome was assessed after 2–6 months according to the Cerebral Performance Category scale. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: In 794 included patients, median age was 69.5 years (interquartile range, 60.6–77.0 yr), 241 (30.4%) were female, 550 (69.3%) had an out-of-hospital cardiac arrest, and 314 (41.3%) had a shockable rhythm. Four hundred ninety-five patients were dead at follow-up, 330 of 495 died after a decision on withdrawal of life-sustaining therapies. At 72 hours after cardiac arrest 218 patients remained unconscious. The entry criteria of the original algorithm (GCS-M 1–3) was fulfilled by 163 patients and 115 patients with poor outcome were identified, with false positive rate (FPR) of 0% (95% CI, 0–79.4%) and sensitivity of 71.0% (95% CI, 63.6–77.4%). Inclusion of patients with ongoing sedation identified another 13 patients with poor outcome, generating FPR of 0% (95% CI, 0–65.8%) and sensitivity of 69.6% (95% CI, 62.6–75.8%). Inclusion of all unconscious patients (GCS-M 1–5), regardless of sedation, identified one additional patient, generating FPR of 0% (95% CI, 0–22.8) and sensitivity of 62.9% (95% CI, 56.1–69.2). The few patients with true negative prediction (patients with good outcome not fulfilling guideline criteria of a poor outcome) generated wide 95% CI for FPR. CONCLUSION: The 2021 ERC/ESICM algorithm for neuroprognostication predicted poor neurologic outcome with a FPR of 0%. Broadening inclusion criteria to include all unconscious patients regardless of ongoing sedation identified an additional small number of patients with poor outcome but did not affect the FPR. Results are limited by high rate of withdrawal of life-sustaining therapies and few patients with true negative prediction.
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| 3. |
- Arctaedius, Isabelle, et al.
(author)
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Plasma glial fibrillary acidic protein and tau: predictors of neurological outcome after cardiac arrest.
- 2024
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In: Critical care (London, England). - 1364-8535 .- 1466-609X. ; 28:1
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Journal article (peer-reviewed)abstract
- The purpose was to evaluate glial fibrillary acidic protein (GFAP) and total-tau in plasma as predictors of poor neurological outcome after out-of-hospital (OHCA) and in-hospital cardiac arrest (IHCA), including comparisons with neurofilament light (NFL) and neuron-specific enolase (NSE).Retrospective multicentre observational study of patients admitted to an intensive care unit (ICU) in three hospitals in Sweden 2014-2018. Blood samples were collected at ICU admission, 12h, and 48h post-cardiac arrest. Poor neurological outcome was defined as Cerebral Performance Category 3-5 at 2-6months after cardiac arrest. Plasma samples were retrospectively analysed for GFAP, tau, and NFL. Serum NSE was analysed in clinical care. Prognostic performances were tested with the area under the receiver operating characteristics curve (AUC).Of the 428 included patients, 328 were OHCA, and 100 were IHCA. At ICU admission, 12h and 48h post-cardiac arrest, GFAP predicted neurological outcome after OHCA with AUC (95% CI) 0.76 (0.70-0.82), 0.86 (0.81-0.90) and 0.91 (0.87-0.96), and after IHCA with AUC (95% CI) 0.77 (0.66-0.87), 0.83 (0.74-0.92) and 0.83 (0.71-0.95). At the same time points, tau predicted outcome after OHCA with AUC (95% CI) 0.72 (0.66-0.79), 0.75 (0.69-0.81), and 0.93 (0.89-0.96) and after IHCA with AUC (95% CI) 0.61 (0.49-0.74), 0.68 (0.56-0.79), and 0.77 (0.65-0.90). Adding the change in biomarker levels between time points did not improve predictive accuracy compared to the last time point. In a subset of patients, GFAP at 12h and 48 h, as well as tau at 48h, offered similar predictive value as NSE at 48h (the earliest time point NSE is recommended in guidelines) after both OHCA and IHCA. The predictive performance of NFL was similar or superior to GFAP and tau at all time points after OHCA and IHCA.GFAP and tau are promising biomarkers for neuroprognostication, with the highest predictive performance at 48h after OHCA, but not superior to NFL. The predictive ability of GFAP may be sufficiently high for clinical use at 12h after cardiac arrest.
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| 4. |
- Dankiewicz, Josef, et al.
(author)
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Hypothermia versus Normothermia after Out-of-Hospital Cardiac Arrest
- 2021
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In: New England Journal of Medicine. - : MASSACHUSETTS MEDICAL SOC. - 0028-4793 .- 1533-4406. ; 384:24, s. 2283-2294
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Journal article (peer-reviewed)abstract
- Hypothermia or Normothermia after Cardiac Arrest This trial randomly assigned patients with coma after out-of-hospital cardiac arrest to undergo targeted hypothermia at 33 degrees C or normothermia with treatment of fever. At 6 months, there were no significant between-group differences regarding death or functional outcomes. Background Targeted temperature management is recommended for patients after cardiac arrest, but the supporting evidence is of low certainty. Methods In an open-label trial with blinded assessment of outcomes, we randomly assigned 1900 adults with coma who had had an out-of-hospital cardiac arrest of presumed cardiac or unknown cause to undergo targeted hypothermia at 33 degrees C, followed by controlled rewarming, or targeted normothermia with early treatment of fever (body temperature, >= 37.8 degrees C). The primary outcome was death from any cause at 6 months. Secondary outcomes included functional outcome at 6 months as assessed with the modified Rankin scale. Prespecified subgroups were defined according to sex, age, initial cardiac rhythm, time to return of spontaneous circulation, and presence or absence of shock on admission. Prespecified adverse events were pneumonia, sepsis, bleeding, arrhythmia resulting in hemodynamic compromise, and skin complications related to the temperature management device. Results A total of 1850 patients were evaluated for the primary outcome. At 6 months, 465 of 925 patients (50%) in the hypothermia group had died, as compared with 446 of 925 (48%) in the normothermia group (relative risk with hypothermia, 1.04; 95% confidence interval [CI], 0.94 to 1.14; P=0.37). Of the 1747 patients in whom the functional outcome was assessed, 488 of 881 (55%) in the hypothermia group had moderately severe disability or worse (modified Rankin scale score >= 4), as compared with 479 of 866 (55%) in the normothermia group (relative risk with hypothermia, 1.00; 95% CI, 0.92 to 1.09). Outcomes were consistent in the prespecified subgroups. Arrhythmia resulting in hemodynamic compromise was more common in the hypothermia group than in the normothermia group (24% vs. 17%, P<0.001). The incidence of other adverse events did not differ significantly between the two groups. Conclusions In patients with coma after out-of-hospital cardiac arrest, targeted hypothermia did not lead to a lower incidence of death by 6 months than targeted normothermia. (Funded by the Swedish Research Council and others; TTM2 ClinicalTrials.gov number, .)
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| 5. |
- Dankiewicz, Josef, et al.
(author)
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Targeted hypothermia versus targeted Normothermia after out-of-hospital cardiac arrest (TTM2): A randomized clinical trial - Rationale and design
- 2019
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In: American Heart Journal. - : Elsevier BV. - 0002-8703 .- 1097-6744. ; 217, s. 23-31
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Journal article (peer-reviewed)abstract
- Background: Less than 500 participants have been included in randomized trials comparing hypothermia with regular care for out-of-hospital cardiac arrest patients, and many of these trials were small and at a high risk of bias. Consequently, the accrued data on this potentially beneficial intervention resembles that of a drug following small phase II trials. A large confirmatory trial is therefore warranted. Methods: The TTM2-trial is an international, multicenter, parallel group, investigator-initiated, randomized, superiority trial in which a target temperature of 33°C after cardiac arrest will be compared with a strategy to maintain normothermia and early treatment of fever (≥37.8°C). Participants will be randomized within 3 hours of return of spontaneous circulation with the intervention period lasting 40 hours in both groups. Sedation will be mandatory for all patients throughout the intervention period. The clinical team involved with direct patient care will not be blinded to allocation group due to the inherent difficulty in blinding the intervention. Prognosticators, outcome-assessors, the steering group, the trial coordinating team, and trial statistician will be blinded. The primary outcome will be all-cause mortality at 180 days after randomization. We estimate a 55% mortality in the control group. To detect an absolute risk reduction of 7.5% with an alpha of 0.05 and 90% power, 1900 participants will be enrolled. The main secondary neurological outcome will be poor functional outcome (modified Rankin Scale 4–6) at 180 days after arrest. Discussion: The TTM2-trial will compare hypothermia to 33°C with normothermia and early treatment of fever (≥37.8°C) after out-of-hospital cardiac arrest. © 2019
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| 6. |
- Frigyesi, Attila, et al.
(author)
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Circulating dipeptidyl peptidase 3 on intensive care unit admission is a predictor of organ dysfunction and mortality
- 2021
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In: Journal of Intensive Care. - : Springer Science and Business Media LLC. - 2052-0492. ; 9:1
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Journal article (peer-reviewed)abstract
- BACKGROUND: Our aim was to investigate the prognostic potential of circulating dipeptidyl peptidase 3 (cDPP3) to predict mortality and development of organ dysfunction in a mixed intensive care unit (ICU) population, and for this reason, we analysed prospectively collected admission blood samples from adult ICU patients at four Swedish hospitals. Blood samples were stored in a biobank for later batch analysis. The association of cDPP3 levels with 30-day mortality and Sequential Organ Failure Assessment (SOFA) scores on day two was investigated before and after adjustment for the simplified acute physiology score III (SAPS-3), using multivariable (ordinal) logistic regression. The predictive power of cDPP3 was assessed using the area under the receiver operating characteristic curve (AUROC).RESULTS: Of 1978 included consecutive patients in 1 year (2016), 632 fulfilled the sepsis 3-criteria, 190 were admitted after cardiac arrest, and 157 because of trauma. Admission cDPP3 was independently (of SAPS-3) associated with 30-day mortality with odds ratios of 1.45 (95% confidence interval (CI) 1.28-1.64) in the entire ICU population, 1.30 (95% CI 1.08-1.57) in the sepsis subgroup and 2.28 (95% CI 1.50-3.62) in cardiac arrest. For trauma, there was no clear association. Circulating DPP3 alone was a moderate predictor of 30-day mortality with AUROCs of 0.68, 0.62, and 0.72 in the entire group, the sepsis subgroup, and the cardiac arrest subgroup, respectively. By adding cDPP3 to SAPS-3, AUROC improved for the entire group, the sepsis subgroup, and the cardiac arrest subgroup (p = 0.023).CONCLUSION: Circulating DPP3 on admission is a SAPS-3 independent prognostic factor of day-two organ dysfunction and 30-day mortality in a mixed ICU population and needs further evaluation.
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| 7. |
- Frigyesi, Attila, et al.
(author)
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Plasma proenkephalin A 119-159 on intensive care unit admission is a predictor of organ failure and 30-day mortality
- 2021
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In: Intensive Care Medicine Experimental. - : Springer Science and Business Media LLC. - 2197-425X. ; 9:1
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Journal article (peer-reviewed)abstract
- BACKGROUND: Proenkephalin A 119-159 (penKid) has been suggested as a marker of renal failure and poor outcome. We aimed to investigate the association of penKid on ICU admission with organ dysfunction and mortality in a mixed ICU population. In this retrospective, observational study, admission penKid levels from prospectively collected blood samples of consecutive patients admitted to four Swedish ICUs were analysed. The association of penKid with day-two sequential organ failure assessment (SOFA) scores and 30-day mortality was investigated using (ordinal) logistic regression. The predictive power of penKid for 30-day mortality and dialysis was assessed using the area under the receiver operating characteristic curve (AUC).RESULTS: Of 1978 included patients, 632 fulfilled the sepsis 3-criteria, 190 had a cardiac arrest, and 157 had experienced trauma. Admission penKid was positively associated with 30-day mortality with an odds ratio of 1.95 (95% confidence interval 1.75-2.18, p < 0.001), and predicted 30-day mortality in the entire ICU population with an AUC of 0.71 (95% confidence interval 0.68-0.73) as well as in the sepsis, cardiac arrest and trauma subgroups (AUCs of 0.61-0.84). Correction for admission plasma creatinine revealed that penKid correlated with neurological dysfunction.CONCLUSION: Plasma penKid on ICU admission is associated with day-two organ dysfunction and predictive of 30-day mortality in a mixed ICU-population, as well as in sepsis, cardiac arrest and trauma subgroups. In addition to being a marker of renal dysfunction, plasma penKid is associated with neurologic dysfunction in the entire ICU population, and cardiovascular dysfunction in sepsis.
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| 8. |
- Frigyesi, Attila, et al.
(author)
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Provsamlingen Swecrit och AI ger ny kunskap vid intensivvård
- 2023
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In: Lakartidningen. - 0023-7205. ; 120:42, s. 1-5
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Journal article (other academic/artistic)abstract
- The unique Swecrit Biobank and its associated clinical registries for sepsis, ARDS, cardiac arrest, trauma, and COVID-19 include more than 150,000 blood samples and descriptions of critically ill patients. These assets provide a unique opportunity to research and improve the care of the most seriously ill patients through biomarker analyses, proteomic studies, and genetic and epigenetic studies using modern machine learning techniques (artificial intelligence). Interested researchers are invited to submit their proposals and participate.
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| 9. |
- Holgersson, Johan, et al.
(author)
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Hypothermic versus Normothermic Temperature Control after Cardiac Arrest
- 2022
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In: NEJM Evidence. - 2766-5526. ; 1:11, s. 1-13
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Journal article (peer-reviewed)abstract
- BACKGROUNDThe evidence for temperature control for comatose survivors of cardiac arrest is inconclusive. Controversy exists as to whether the effects of hypothermia differ per the circumstances of the cardiac arrest or patient characteristics.METHODSAn individual patient data meta-analysis of the Targeted Temperature Management at 33°C versus 36°C after Cardiac Arrest (TTM) and Hypothermia versus Normothermia after Out-of-Hospital Cardiac Arrest (TTM2) trials was conducted. The intervention was hypothermia at 33°C and the comparator was normothermia. The primary outcome was all-cause mortality at 6 months. Secondary outcomes included poor functional outcome (modified Rankin scale score of 4 to 6) at 6 months. Predefined subgroups based on the design variables in the original trials were tested for interaction with the intervention as follows: age (older or younger than the median), sex (female or male), initial cardiac rhythm (shockable or nonshockable), time to return of spontaneous circulation (above or below the median), and circulatory shock on admission (presence or absence).RESULTSThe primary analyses included 2800 patients, with 1403 assigned to hypothermia and 1397 to normothermia. Death occurred for 691 of 1398 participants (49.4%) in the hypothermia group and 666 of 1391 participants (47.9%) in the normothermia group (relative risk with hypothermia, 1.03; 95% confidence interval [CI], 0.96 to 1.11; P=0.41). A poor functional outcome occurred for 733 of 1350 participants (54.3%) in the hypothermia group and 718 of 1330 participants (54.0%) in the normothermia group (relative risk with hypothermia, 1.01; 95% CI, 0.94 to 1.08; P=0.88). Outcomes were consistent in the predefined subgroups.CONCLUSIONSHypothermia at 33°C did not decrease 6-month mortality compared with normothermia after out-of-hospital cardiac arrest. (Funded by Vetenskapsrådet; ClinicalTrials.gov numbers NCT02908308 and NCT01020916.)
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| 10. |
- Jakobsen, Janus Christian, et al.
(author)
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Targeted hypothermia versus targeted normothermia after out-of-hospital cardiac arrest: a statistical analysis plan.
- 2020
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In: Trials. - : Springer Science and Business Media LLC. - 1745-6215. ; 21:1
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Journal article (peer-reviewed)abstract
- To date, targeted temperature management (TTM) is the only neuroprotective intervention after resuscitation from cardiac arrest that is recommended by guidelines. The evidence on the effects of TTM is unclear.The Targeted Hypothermia Versus Targeted Normothermia After Out-of-hospital Cardiac Arrest (TTM2) trial is an international, multicentre, parallel group, investigator-initiated, randomised, superiority trial in which TTM with a target temperature of 33°C after cardiac arrest will be compared with a strategy to maintain normothermia and active treatment of fever (≥37.8°C). Prognosticators, outcome assessors, the steering group, the trial coordinating team, and trial statisticians will be blinded to treatment allocation. The primary outcome will be all-cause mortality at 180days after randomisation. We estimate a 55% mortality in the targeted normothermia group. To detect an absolute risk reduction of 7.5% with an alpha of 0.05 and 90% power, 1900 participants will be enrolled. The secondary neurological outcome will be poor functional outcome (modified Rankin scale 4-6) at 180days after cardiac arrest. In this paper, a detailed statistical analysis plan is presented, including a comprehensive description of the statistical analyses, handling of missing data, and assessments of underlying statistical assumptions. Final analyses will be conducted independently by two qualified statisticians following the present plan.This SAP, which was prepared before completion of enrolment, should increase the validity of the TTM trial by mitigation of analysis-bias.
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| 11. |
- Johansson, Gudrun M., 1963-, et al.
(author)
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The added value of kinematic evaluation of the timed finger-to-nose test in persons post-stroke.
- 2017
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In: Journal of NeuroEngineering and Rehabilitation. - : Springer Science and Business Media LLC. - 1743-0003. ; 14
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Journal article (peer-reviewed)abstract
- BACKGROUND: Upper limb coordination in persons post-stroke may be estimated by the commonly used Finger-to-Nose Test (FNT), which is also part of the Fugl-Meyer Assessment. The total movement time (TMT) is used as a clinical outcome measure, while kinematic evaluation also enables an objective quantification of movement quality and motor performance. Our aims were to kinematically characterize FNT performance in persons post-stroke and controls and to investigate the construct validity of the test in persons with varying levels of impairment post-stroke.METHODS: A three-dimensional motion capture system recorded body movements during performance of the FNT in 33 persons post-stroke who had mild or moderate upper limb motor impairments (Fugl-Meyer scores of 50-62 or 32-49, respectively), and 41 non-disabled controls. TMT and kinematic variables of the hand (pointing time, peak speed, time to peak speed, number of movement units, path ratio, and pointing accuracy), elbow/shoulder joints (range of motion, interjoint coordination), and scapular/trunk movement were calculated. Our analysis focused on the pointing phase (knee to nose movement of the FNT). Independent t or Mann-Whitney U tests and effect sizes were used to analyze group differences. Sub-group analyses based on movement time and stroke severity were performed. Within the stroke group, simple and multiple linear regression were used to identify relationships between TMT to kinematic variables.RESULTS: The stroke group had significant slower TMT (mean difference 2.6 s, d = 1.33) than the control group, and six other kinematic variables showed significant group differences. At matched speeds, the stroke group had lower accuracy and excessive scapular and trunk movements compared to controls. Pointing time and elbow flexion during the pointing phase were most related to stroke severity. For the stroke group, the number of movement units during the pointing phase showed the strongest association with the TMT, and explained 60% of the TMT variance.CONCLUSIONS: The timed FNT discriminates between persons with mild and moderate upper limb impairments. However, kinematic analysis to address construct validity highlights differences in pointing movement post-stroke that are not captured in the timed FNT.
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| 12. |
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| 13. |
- Lengquist, Maria, et al.
(author)
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Sepsis Is Underreported in Swedish Intensive Care Units: A Retrospective Observational Multicentre Study
- 2020
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In: Acta Anaesthesiologica Scandinavica. - : Wiley. - 0001-5172 .- 1399-6576. ; , s. 1167-1167
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Journal article (peer-reviewed)abstract
- BackgroundSepsis is a common indication for admission to the intensive care unit (ICU). Since definitions vary across studies, comparisons of prevalence and outcomes have been challenging. We aimed to compare sepsis according to ICU discharge codes with sepsis according to Sepsis‐3 criteria and to investigate the epidemiology of sepsis in the ICU. We hypothesized that sepsis using discharge codes is underreported.MethodsAdult ICU admissions to four ICUs in Sweden between 2015 and 2017 were screened for sepsis according to the Sepsis‐3 criteria. Medical records were reviewed and data extracted from the Swedish Intensive Care Registry.ResultsOf 5990 adult ICU patients, 28% fulfilled the Sepsis‐3 criteria on admission, but only 31% of them had sepsis as the registered main diagnosis at ICU discharge. Of the 1654 Sepsis‐3 patients, 38% met the septic shock criteria. The Sepsis‐3 in‐hospital mortality was 26% compared to 33% in patients with septic shock. The incidence rate for ICU‐treated sepsis was 81 cases per 100 000 person‐years. One in four had a positive blood culture, and 44% were culture negative.ConclusionThis large Swedish multicentre study showed that 28% of adult ICU patients fulfilled the Sepsis‐3 criteria, but only one third of them had sepsis according to ICU discharge codes. We could confirm our hypothesis, that sepsis is severely underreported in Swedish ICUs, and we conclude that discharge codes should not be used for quality control or research purposes.
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| 14. |
- Levin, Helena, et al.
(author)
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Plasma neurofilament light is a predictor of neurological outcome 12 h after cardiac arrest
- 2023
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In: Critical Care. - : Springer Science and Business Media LLC. - 1364-8535. ; 27:1
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Journal article (peer-reviewed)abstract
- BackgroundPrevious studies have reported high prognostic accuracy of circulating neurofilament light (NfL) at 24-72 h after out-of-hospital cardiac arrest (OHCA), but performance at earlier time points and after in-hospital cardiac arrest (IHCA) is less investigated. We aimed to assess plasma NfL during the first 48 h after OHCA and IHCA to predict long-term outcomes.MethodsObservational multicentre cohort study in adults admitted to intensive care after cardiac arrest. NfL was retrospectively analysed in plasma collected on admission to intensive care, 12 and 48 h after cardiac arrest. The outcome was assessed at two to six months using the Cerebral Performance Category (CPC) scale, where CPC 1-2 was considered a good outcome and CPC 3-5 a poor outcome. Predictive performance was measured with the area under the receiver operating characteristic curve (AUROC).ResultsOf 428 patients, 328 (77%) suffered OHCA and 100 (23%) IHCA. Poor outcome was found in 68% of OHCA and 55% of IHCA patients. The overall prognostic performance of NfL was excellent at 12 and 48 h after OHCA, with AUROCs of 0.93 and 0.97, respectively. The predictive ability was lower after IHCA than OHCA at 12 and 48 h, with AUROCs of 0.81 and 0.86 (p <= 0.03). AUROCs on admission were 0.77 and 0.67 after OHCA and IHCA, respectively. At 12 and 48 h after OHCA, high NfL levels predicted poor outcome at 95% specificity with 70 and 89% sensitivity, while low NfL levels predicted good outcome at 95% sensitivity with 71 and 74% specificity and negative predictive values of 86 and 88%.ConclusionsThe prognostic accuracy of NfL for predicting good and poor outcomes is excellent as early as 12 h after OHCA. NfL is less reliable for the prediction of outcome after IHCA.
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| 15. |
- Lileikyte, Gabriele, et al.
(author)
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Serum proteome profiles in patients treated with targeted temperature management after out-of-hospital cardiac arrest
- 2023
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In: Intensive Care Medicine Experimental. - 2197-425X. ; 11:1
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Journal article (peer-reviewed)abstract
- BACKGROUND: Definition of temporal serum proteome profiles after out-of-hospital cardiac arrest may identify biological processes associated with severe hypoxia-ischaemia and reperfusion. It may further explore intervention effects for new mechanistic insights, identify candidate prognostic protein biomarkers and potential therapeutic targets. This pilot study aimed to investigate serum proteome profiles from unconscious patients admitted to hospital after out-of-hospital cardiac arrest according to temperature treatment and neurological outcome.METHODS: Serum samples at 24, 48, and 72 h after cardiac arrest at three centres included in the Target Temperature Management after out-of-hospital cardiac arrest trial underwent data-independent acquisition mass spectrometry analysis (DIA-MS) to find changes in serum protein concentrations associated with neurological outcome at 6-month follow-up and targeted temperature management (TTM) at 33 °C as compared to 36 °C. Neurological outcome was defined according to Cerebral Performance Category (CPC) scale as "good" (CPC 1-2, good cerebral performance or moderate disability) or "poor" (CPC 3-5, severe disability, unresponsive wakefulness syndrome, or death).RESULTS: Of 78 included patients [mean age 66 ± 12 years, 62 (80.0%) male], 37 (47.4%) were randomised to TTM at 36 °C. Six-month outcome was poor in 47 (60.3%) patients. The DIA-MS analysis identified and quantified 403 unique human proteins. Differential protein abundance testing comparing poor to good outcome showed 19 elevated proteins in patients with poor outcome (log 2-fold change (FC) range 0.28-1.17) and 16 reduced proteins (log 2(FC) between - 0.22 and - 0.68), involved in inflammatory/immune responses and apoptotic signalling pathways for poor outcome and proteolysis for good outcome. Analysis according to level of TTM showed a significant protein abundance difference for six proteins [five elevated proteins in TTM 36 °C (log 2(FC) between 0.33 and 0.88), one reduced protein (log 2(FC) - 0.6)] mainly involved in inflammatory/immune responses only at 48 h after cardiac arrest. CONCLUSIONS: Serum proteome profiling revealed an increase in inflammatory/immune responses and apoptosis in patients with poor outcome. In patients with good outcome, an increase in proteolysis was observed, whereas TTM-level only had a modest effect on the proteome profiles. Further validation of the differentially abundant proteins in response to neurological outcome is necessary to validate novel biomarker candidates that may predict prognosis after cardiac arrest.
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| 16. |
- Lilja, Gisela, et al.
(author)
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Effects of Hypothermia vs Normothermia on Societal Participation and Cognitive Function at 6 Months in Survivors After Out-of-Hospital Cardiac Arrest A Predefined Analysis of the TTM2 Randomized Clinical Trial
- 2023
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In: Jama Neurology. - 2168-6149 .- 2168-6157. ; 80:10, s. 1070-1079
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Journal article (peer-reviewed)abstract
- IMPORTANCE The Targeted Hypothermia vs Targeted Normothermia After Out-of-Hospital Cardiac Arrest (TTM2) trial reported no difference in mortality or poor functional outcome at 6 months after out-of-hospital cardiac arrest (OHCA). This predefined exploratory analysis provides more detailed estimation of brain dysfunction for the comparison of the 2 intervention regimens. OBJECTIVES To investigate the effects of targeted hypothermia vs targeted normothermia on functional outcome with focus on societal participation and cognitive function in survivors 6 months after OHCA. DESIGN, SETTING, AND PARTICIPANTS This study is a predefined analysis of an international multicenter, randomized clinical trial that took place from November 2017 to January 2020 and included participants at 61 hospitals in 14 countries. A structured follow-up for survivors performed at 6 months was by masked outcome assessors. The last follow-up took place in October 2020. Participants included 1861 adult (older than 18 years) patients with OHCA who were comatose at hospital admission. At 6 months, 939 of 1861 were alive and invited to a follow-up, of which 103 of 939 declined or were missing. INTERVENTIONS Randomization 1:1 to temperature control with targeted hypothermia at 33 degrees C or targeted normothermia and early treatment of fever (37.8 degrees C or higher). MAIN OUTCOMES AND MEASURES Functional outcome focusing on societal participation assessed by the Glasgow Outcome Scale Extended ([GOSE] 1 to 8) and cognitive function assessed by the Montreal Cognitive Assessment ([MoCA] 0 to 30) and the Symbol Digit Modalities Test ([SDMT] z scores). Higher scores represent better outcomes. RESULTS At 6 months, 836 of 939 survivors with a mean age of 60 (SD, 13) (range, 18 to 88) years (700 of 836 male [84%]) participated in the follow-up. There were no differences between the 2 intervention groups in functional outcome focusing on societal participation (GOSE score, odds ratio, 0.91; 95% CI, 0.71-1.17; P =.46) or in cognitive function by MoCA (mean difference, 0.36; 95% CI,-0.33 to 1.05; P =.37) and SDMT (mean difference, 0.06; 95% CI,-0.16 to 0.27; P =.62). Limitations in societal participation (GOSE score less than 7) were common regardless of intervention (hypothermia, 178 of 415 [43%]; normothermia, 168 of 419 [40%]). Cognitive impairment was identified in 353 of 599 survivors (59%). CONCLUSIONS In this predefined analysis of comatose patients after OHCA, hypothermia did not lead to better functional outcome assessed with a focus on societal participation and cognitive function than management with normothermia. At 6 months, many survivors had not regained their pre-arrest activities and roles, and mild cognitive dysfunction was common.
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| 17. |
- Lilja, Gisela, et al.
(author)
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Protocol for outcome reporting and follow-up in the Targeted Hypothermia versus Targeted Normothermia after Out-of-Hospital Cardiac Arrest trial (TTM2)
- 2020
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In: Resuscitation. - : Elsevier BV. - 0300-9572 .- 1873-1570. ; 150, s. 104-112
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Journal article (peer-reviewed)abstract
- Aims: The TTM2-trial is a multi-centre randomised clinical trial where targeted temperature management (TTM) at 33 °C will be compared with normothermia and early treatment of fever (≥37.8 °C) after Out-of-Hospital Cardiac Arrest (OHCA). This paper presents the design and rationale of the TTM2-trial follow-up, where information on secondary and exploratory outcomes will be collected. We also present the explorative outcome analyses which will focus on neurocognitive function and societal participation in OHCA-survivors. Methods: Blinded outcome-assessors will perform follow-up at 30-days after the OHCA with a telephone interview, including the modified Rankin Scale (mRS) and the Glasgow Outcome Scale Extended (GOSE). Face-to-face meetings will be performed at 6 and 24-months, and include reports on outcome from several sources of information: clinician-reported: mRS, GOSE; patient-reported: EuroQol-5 Dimensions-5 Level responses version (EQ-5D-5L), Life satisfaction, Two Simple Questions; observer-reported: Informant Questionnaire on Cognitive Decline in the Elderly-Cardiac Arrest version (IQCODE-CA) and neurocognitive performance measures: Montreal Cognitive Assessment, (MoCA), Symbol Digit Modalities Test (SDMT). Exploratory analyses will be performed with an emphasis on brain injury in the survivors, where the two intervention groups will be compared for potential differences in neuro-cognitive function (MoCA, SDMT) and societal participation (GOSE). Strategies to increase inter-rater reliability and decrease missing data are described. Discussion: The TTM2-trial follow-up is a pragmatic yet detailed pre-planned and standardised assessment of patient's outcome designed to ensure data-quality, decrease missing data and provide optimal conditions to investigate clinically relevant effects of TTM, including OHCA-survivors’ neurocognitive function and societal participation.
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| 18. |
- Lindstrand, Anna, et al.
(author)
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Genome sequencing is a sensitive first-line test to diagnose individuals with intellectual disability
- 2022
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In: Genetics in Medicine. - : ELSEVIER SCIENCE INC. - 1098-3600 .- 1530-0366. ; 24:11, s. 2296-2307
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Journal article (peer-reviewed)abstract
- Purpose: Individuals with intellectual disability (ID) and/or neurodevelopment disorders (NDDs) are currently investigated with several different approaches in clinical genetic diagnostics. Methods: We compared the results from 3 diagnostic pipelines in patients with ID/NDD: genome sequencing (GS) first (N = 100), GS as a secondary test (N = 129), or chromosomal microarray (CMA) with or without FMR1 analysis (N = 421). Results: The diagnostic yield was 35% (GS -first), 26% (GS as a secondary test), and 11% (CMA/FMR1). Notably, the age of diagnosis was delayed by 1 year when GS was performed as a secondary test and the cost per diagnosed individual was 36% lower with GS first than with CMA/FMR1. Furthermore, 91% of those with a negative result after CMA/FMR1 analysis (338 individuals) have not yet been referred for additional genetic testing and remain undiagnosed. Conclusion: Our findings strongly suggest that genome analysis outperforms other testing strategies and should replace traditional CMA and FMR1 analysis as a first-line genetic test in individuals with ID/NDD. GS is a sensitive, time-and cost-effective method that results in a confirmed molecular diagnosis in 35% of all referred patients. (c) 2022 The Authors. Published by Elsevier Inc. on behalf of American College of Medical Genetics and Genomics. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
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| 19. |
- Lissner Östlund, Emilie, et al.
(author)
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Neuron-specific enolase and long-term neurological outcome after OHCA – A validation study
- 2021
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In: Resuscitation. - : Elsevier BV. - 0300-9572. ; 168, s. 206-213
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Journal article (peer-reviewed)abstract
- Aims: To investigate what NSE levels predict long-term neurological prognosis at 24, 48 and 72 hours after ROSC in a cohort of out-of-hospital cardiac arrest and to validate previously suggested NSE cut-offs, including the latest ERC guidelines (2021). Methods: Patients admitted to intensive care units in four hospitals in Southern Sweden between 2014–2018 were included. Blood samples were handled by a single local laboratory. The primary outcome was neurological outcome according to the Cerebral Performance Category (CPC) scale at 2–6 months after cardiac arrest. Results: 368 patients were included for analysis. A ≤2% false positive rate for the prediction of poor neurological outcome was achieved with an NSE cut-off value of >101 μg/L at 48 hours and >80 μg/L at 72 hours. The cut-off suggested by the recent ERC guidelines of >60 μg/L at 48 and/or 72 hours generated a false positive rate of 4.3% (95 %CI 0.9–7.4%). Conclusion: A local validation study of the ability of serum levels of neuron-specific enolase to predict long-term poor neurological outcome after out-of-hospital cardiac arrest generated higher cut-offs than suggested by previous publications.
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| 20. |
- Lundberg, Oscar H.M., et al.
(author)
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Circulating bioactive adrenomedullin as a marker of sepsis, septic shock and critical illness
- 2020
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In: Critical Care. - : Springer Science and Business Media LLC. - 1364-8535. ; 24:1
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Journal article (peer-reviewed)abstract
- Background: Biomarkers can be of help to understand critical illness and to identify and stratify sepsis. Adrenomedullin is a vasoactive hormone, with reported prognostic and potentially therapeutic value in sepsis. The primary aim of this study was to investigate the association of circulating bioactive adrenomedullin (bio-ADM) levels at intensive care unit (ICU) admission with mortality in sepsis patients and in a general ICU population. Secondary aims included the association of bio-ADM with organ failure and the ability of bio-ADM to identify sepsis. Methods: In this retrospective observational study, adult patients admitted to one of four ICUs during 2016 had admission bio-ADM levels analysed. Age-adjusted odds ratios (OR) with 95% CI for log-2 transformed bio-ADM, and Youden’s index derived cut-offs were calculated. The primary outcome was 30-day mortality, and secondary outcomes included the need for organ support and the ability to identify sepsis. Results: Bio-ADM in 1867 consecutive patients were analysed; 632 patients fulfilled the sepsis-3 criteria of whom 267 had septic shock. The median bio-ADM in the entire ICU population was 40 pg/mL, 74 pg/mL in sepsis patients, 107 pg/mL in septic shock and 29 pg/mL in non-septic patients. The association of elevated bio-ADM and mortality in sepsis patients and the ICU population resulted in ORs of 1.23 (95% CI 1.07–1.41) and 1.22 (95% CI 1.12–1.32), respectively. The association with mortality remained after additional adjustment for lactate in sepsis patients. Elevated bio-ADM was associated with an increased need for dialysis with ORs of 2.28 (95% CI 2.01–2.59) and 1.97 (95% CI 1.64–2.36) for the ICU population and sepsis patients, respectively, and with increased need of vasopressors, OR 1.33 (95% CI 1.23–1.42) (95% CI 1.17–1.50) for both populations. Sepsis was identified with an OR of 1.78 (95% CI 1.64–1.94) for bio-ADM, after additional adjustment for severity of disease. A bio-ADM cut-off of 70 pg/mL differentiated between survivors and non-survivors in sepsis, but a Youden’s index derived threshold of 108 pg/mL performed better. Conclusions: Admission bio-ADM is associated with 30-day mortality and organ failure in sepsis patients as well as in a general ICU population. Bio-ADM may be a morbidity-independent sepsis biomarker.
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| 21. |
- Mazor, G., et al.
(author)
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The lncRNA TP73-AS1 is linked to aggressiveness in glioblastoma and promotes temozolomide resistance in glioblastoma cancer stem cells
- 2019
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In: Cell Death & Disease. - : Springer Science and Business Media LLC. - 2041-4889. ; 10:3
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Journal article (peer-reviewed)abstract
- Glioblastoma multiform (GBM) is the most common brain tumor characterized by a dismal prognosis. GBM cancer stem cells (gCSC) or tumor-initiating cells are the cell population within the tumor-driving therapy resistance and recurrence. While temozolomide (TMZ), an alkylating agent, constitutes the first-line chemotherapeutic significantly improving survival in GBM patients, resistance against this compound commonly leads to GBM recurrence and treatment failure. Although the roles of protein-coding transcripts, proteins and microRNA in gCSC, and therapy resistance have been comprehensively investigated, very little is known about the role of long noncoding RNAs (lncRNAs) in this context. Using nonoverlapping, independent RNA sequencing and gene expression profiling datasets, we reveal that TP73-AS1 constitutes a clinically relevant lncRNA in GBM. Specifically, we demonstrate significant overexpression of TP73-AS1 in primary GBM samples, which is particularly increased in the gCSC. More importantly, we demonstrate that TP73-AS1 comprises a prognostic biomarker in glioma and in GBM with high expression identifying patients with particularly poor prognosis. Using CRISPRi to downregulate our candidate lncRNA in gCSC, we demonstrate that TP73-AS1 promotes TMZ resistance in gCSC and is linked to regulation of the expression of metabolism- related genes and ALDH1A1, a protein known to be expressed in cancer stem cell markers and protects gCSC from TMZ treatment. Taken together, our results reveal that high TP73-AS1 predicts poor prognosis in primary GBM cohorts and that this lncRNA promotes tumor aggressiveness and TMZ resistance in gCSC.
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| 22. |
- Moseby-Knappe, Marion, et al.
(author)
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Biomarkers of brain injury after cardiac arrest; a statistical analysis plan from the TTM2 trial biobank investigators
- 2022
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In: Resuscitation Plus. - : Elsevier. - 2666-5204. ; 10
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Journal article (peer-reviewed)abstract
- Background: Several biochemical markers in blood correlate with the magnitude of brain injury and may be used to predict neurological outcome after cardiac arrest. We present a protocol for the evaluation of prognostic accuracy of brain injury markers after cardiac arrest. The aim is to define the best predictive marker and to establish clinically useful cut-off levels for routine implementation. Methods: Prospective international multicenter trial within the Targeted Hypothermia versus Targeted Normothermia after Out-of-Hospital Cardiac Arrest (TTM2) trial in collaboration with Roche Diagnostics International AG. Samples were collected 0, 24, 48, and 72 hours after randomisation (serum) and 0 and 48 hours after randomisation (plasma), and pre-analytically processed at each site before storage in a central biobank. Routine markers neuron-specific enolase (NSE) and S100B, and neurofilament light, total-tau and glial fibrillary acidic protein will be batch analysed using novel Elecsys (R) electrochemiluminescence immunoassays on a Cobas e601 instrument. Results: Statistical analysis will be reported according to the Standards for Reporting Diagnostic accuracy studies (STARD) and will include comparisons for prediction of good versus poor functional outcome at six months post-arrest, by modified Rankin Scale (0-3 vs. 4-6), using logistic regression models and receiver operating characteristics curves, evaluation of mortality at six months according to biomarker levels and establishment of cut-off values for prediction of poor neurological outcome at 95-100% specificities. Conclusions: This prospective trial may establish a standard methodology and clinically appropriate cut-off levels for the optimal biomarker of brain injury which predicts poor neurological outcome after cardiac arrest.
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| 23. |
- Robba, Chiara, et al.
(author)
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Oxygen targets and 6-month outcome after out of hospital cardiac arrest : a pre-planned sub-analysis of the targeted hypothermia versus targeted normothermia after Out-of-Hospital Cardiac Arrest (TTM2) trial
- 2022
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In: Critical Care. - : Springer Science and Business Media LLC. - 1364-8535 .- 1466-609X. ; 26, s. 1-13
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Journal article (peer-reviewed)abstract
- Background: Optimal oxygen targets in patients resuscitated after cardiac arrest are uncertain. The primary aim of this study was to describe the values of partial pressure of oxygen values (PaO2) and the episodes of hypoxemia and hyperoxemia occurring within the first 72 h of mechanical ventilation in out of hospital cardiac arrest (OHCA) patients. The secondary aim was to evaluate the association of PaO2 with patients’ outcome. Methods: Preplanned secondary analysis of the targeted hypothermia versus targeted normothermia after OHCA (TTM2) trial. Arterial blood gases values were collected from randomization every 4 h for the first 32 h, and then, every 8 h until day 3. Hypoxemia was defined as PaO2 < 60 mmHg and severe hyperoxemia as PaO2 > 300 mmHg. Mortality and poor neurological outcome (defined according to modified Rankin scale) were collected at 6 months. Results: 1418 patients were included in the analysis. The mean age was 64 ± 14 years, and 292 patients (20.6%) were female. 24.9% of patients had at least one episode of hypoxemia, and 7.6% of patients had at least one episode of severe hyperoxemia. Both hypoxemia and hyperoxemia were independently associated with 6-month mortality, but not with poor neurological outcome. The best cutoff point associated with 6-month mortality for hypoxemia was 69 mmHg (Risk Ratio, RR = 1.009, 95% CI 0.93–1.09), and for hyperoxemia was 195 mmHg (RR = 1.006, 95% CI 0.95–1.06). The time exposure, i.e., the area under the curve (PaO2-AUC), for hyperoxemia was significantly associated with mortality (p = 0.003). Conclusions: In OHCA patients, both hypoxemia and hyperoxemia are associated with 6-months mortality, with an effect mediated by the timing exposure to high values of oxygen. Precise titration of oxygen levels should be considered in this group of patients. Trial registration: clinicaltrials.gov NCT02908308, Registered September 20, 2016.
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| 24. |
- Robba, Chiara, et al.
(author)
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Ventilatory settings in the initial 72 h and their association with outcome in out-of-hospital cardiac arrest patients : a preplanned secondary analysis of the targeted hypothermia versus targeted normothermia after out-of-hospital cardiac arrest (TTM2) trial
- 2022
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In: Intensive Care Medicine. - : Springer Science and Business Media LLC. - 0342-4642 .- 1432-1238. ; 48:8, s. 1024-1038
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Journal article (peer-reviewed)abstract
- Purpose: The optimal ventilatory settings in patients after cardiac arrest and their association with outcome remain unclear. The aim of this study was to describe the ventilatory settings applied in the first 72 h of mechanical ventilation in patients after out-of-hospital cardiac arrest and their association with 6-month outcomes. Methods: Preplanned sub-analysis of the Target Temperature Management-2 trial. Clinical outcomes were mortality and functional status (assessed by the Modified Rankin Scale) 6 months after randomization. Results: A total of 1848 patients were included (mean age 64 [Standard Deviation, SD = 14] years). At 6 months, 950 (51%) patients were alive and 898 (49%) were dead. Median tidal volume (VT) was 7 (Interquartile range, IQR = 6.2–8.5) mL per Predicted Body Weight (PBW), positive end expiratory pressure (PEEP) was 7 (IQR = 5–9) cmH20, plateau pressure was 20 cmH20 (IQR = 17–23), driving pressure was 12 cmH20 (IQR = 10–15), mechanical power 16.2 J/min (IQR = 12.1–21.8), ventilatory ratio was 1.27 (IQR = 1.04–1.6), and respiratory rate was 17 breaths/minute (IQR = 14–20). Median partial pressure of oxygen was 87 mmHg (IQR = 75–105), and partial pressure of carbon dioxide was 40.5 mmHg (IQR = 36–45.7). Respiratory rate, driving pressure, and mechanical power were independently associated with 6-month mortality (omnibus p-values for their non-linear trajectories: p < 0.0001, p = 0.026, and p = 0.029, respectively). Respiratory rate and driving pressure were also independently associated with poor neurological outcome (odds ratio, OR = 1.035, 95% confidence interval, CI = 1.003–1.068, p = 0.030, and OR = 1.005, 95% CI = 1.001–1.036, p = 0.048). A composite formula calculated as [(4*driving pressure) + respiratory rate] was independently associated with mortality and poor neurological outcome. Conclusions: Protective ventilation strategies are commonly applied in patients after cardiac arrest. Ventilator settings in the first 72 h after hospital admission, in particular driving pressure and respiratory rate, may influence 6-month outcomes.
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| 25. |
- Taccone, Fabio Silvio, et al.
(author)
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Hypothermia vs Normothermia in Patients With Cardiac Arrest and Nonshockable Rhythm : A Meta-Analysis
- 2024
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In: JAMA Neurology. - : American Medical Association (AMA). - 2168-6149 .- 2168-6157. ; 81:2, s. 126-133
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Journal article (peer-reviewed)abstract
- Importance International guidelines recommend body temperature control below 37.8 °C in unconscious patients with out-of-hospital cardiac arrest (OHCA); however, a target temperature of 33 °C might lead to better outcomes when the initial rhythm is nonshockable.Objective To assess whether hypothermia at 33 °C increases survival and improves function when compared with controlled normothermia in unconscious adults resuscitated from OHCA with initial nonshockable rhythm.Data Sources Individual patient data meta-analysis of 2 multicenter, randomized clinical trials (Targeted Normothermia after Out-of-Hospital Cardiac Arrest [TTM2; NCT02908308] and HYPERION [NCT01994772]) with blinded outcome assessors. Unconscious patients with OHCA and an initial nonshockable rhythm were eligible for the final analysis.Study Selection The study cohorts had similar inclusion and exclusion criteria. Patients were randomized to hypothermia (target temperature 33 °C) or normothermia (target temperature 36.5 to 37.7 °C), according to different study protocols, for at least 24 hours. Additional analyses of mortality and unfavorable functional outcome were performed according to age, sex, initial rhythm, presence or absence of shock on admission, time to return of spontaneous circulation, lactate levels on admission, and the cardiac arrest hospital prognosis score.Data Extraction and Synthesis Only patients who experienced OHCA and had a nonshockable rhythm with all causes of cardiac arrest were included. Variables from the 2 studies were available from the original data sets and pooled into a unique database and analyzed. Clinical outcomes were harmonized into a single file, which was checked for accuracy of numbers, distributions, and categories. The last day of follow-up from arrest was recorded for each patient. Adjustment for primary outcome and functional outcome was performed using age, gender, time to return of spontaneous circulation, and bystander cardiopulmonary resuscitation.Main Outcomes and Measures The primary outcome was mortality at 3 months; secondary outcomes included unfavorable functional outcome at 3 to 6 months, defined as a Cerebral Performance Category score of 3 to 5.Results A total of 912 patients were included, 490 from the TTM2 trial and 422 from the HYPERION trial. Of those, 442 had been assigned to hypothermia (48.4%; mean age, 65.5 years; 287 males [64.9%]) and 470 to normothermia (51.6%; mean age, 65.6 years; 327 males [69.6%]); 571 patients had a first monitored rhythm of asystole (62.6%) and 503 a presumed noncardiac cause of arrest (55.2%). At 3 months, 354 of 442 patients in the hypothermia group (80.1%) and 386 of 470 patients in the normothermia group (82.1%) had died (relative risk [RR] with hypothermia, 1.04; 95% CI, 0.89-1.20; P = .63). On the last day of follow-up, 386 of 429 in the hypothermia group (90.0%) and 413 of 463 in the normothermia group (89.2%) had an unfavorable functional outcome (RR with hypothermia, 0.99; 95% CI, 0.87-1.15; P = .97). The association of hypothermia with death and functional outcome was consistent across the prespecified subgroups.Conclusions and Relevance In this individual patient data meta-analysis, including unconscious survivors from OHCA with an initial nonshockable rhythm, hypothermia at 33 °C did not significantly improve survival or functional outcome.
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| 26. |
- Thorgeirsdóttir, Bergthóra, et al.
(author)
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Plasma proenkephalin A 119-159 and dipeptidyl peptidase 3 on admission after cardiac arrest help predict long-term neurological outcome
- 2021
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In: Resuscitation. - : Elsevier BV. - 1873-1570 .- 0300-9572. ; 163, s. 108-115
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Journal article (peer-reviewed)abstract
- BACKGROUND: A large proportion of adult survivors of cardiac arrest have a poor neurological outcome. Guidelines recommend multimodal neuro-prognostication no earlier than 72-96 hours after cardiac arrest. There is great interest in earlier prognostic markers, including very early markers at admission. The novel blood biomarkers proenkephalin A 119-159 (penKid), bioactive adrenomedullin (bio-ADM) and circulating dipeptidyl peptidase 3 (cDPP3) have not been previously investigated for the early prognosis of cardiac arrest survivors.METHODS: This multicentre observational study included adult survivors of cardiac arrest admitted to intensive care at four Swedish intensive care units (ICUs) during 2016. Blood samples were collected at ICU admission and batch analysed. The association between admission plasma penKid, bio-ADM and cDPP3 and poor long-term neurological outcome, according to the Cerebral Performance Category (CPC) scale, was assessed by binary logistic regression. Their prognostic performance was assessed using the area under the receiver operating characteristic curve (AUC).RESULTS: A total of 190 patients were included, of which 136 patients had suffered out-of-hospital and 54 patients in-hospital cardiac arrest. Poor long-term neurological outcome was associated with elevated admission plasma concentrations of penKid and cDPP3, but not with bio-ADM. The association for penKid, but not for cDPP3, remained after adjusting for clinical cardiac arrest variables with prognostic value (time to return of spontaneous circulation (ROSC), initial rhythm, admission Glasgow Coma Scale (GCS) motor score and absence of pupillary reflexes). The prognostic performance of above mentioned clinical cardiac arrest variables alone was very good with an AUC of 0.90 (95% confidence interval, CI, 0.86-0.95), but improved further with the addition of penKid resulting in an AUC of 0.93 (95% CI 0.89-0.97, p < 0.026). Plasma penKid and cDPP3 alone provided moderate long-term prognostic information with AUCs of 0.70 and 0.71, respectively.CONCLUSION: After cardiac arrest, admission plasma levels of penKid and cDPP3, but not bio-ADM, predicted long-term neurological outcome. When added to clinical cardiac arrest variables, penKid further improved prognostic performance.
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| 27. |
- Thurber, Andrew R., et al.
(author)
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Stable isotope signatures and methane use by New Zealand cold seep benthos
- 2010
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In: MARINE GEOLOGY. - 0025-3227. ; 272:1-4, s. 260-269
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Journal article (peer-reviewed)abstract
- The carbon isotopic composition of seep faunal tissue represents a time-integrated view of the interaction between biology and the biogeochemical gradients within the environment. Here we provide an initial description of carbon and nitrogen stable isotope signatures of dominant symbiont-bearing megafauna and heterotrophic mega- and macrofauna from 10 methane-seep sites on the continental margin of the North Island of New Zealand (662–1201 m water depth). Isotopic signatures suggest that sulfide oxidation supports symbiont-bearing taxa including solemyid and vesicomyid bivalves, and methanotrophic symbionts are present in the seep mussel Bathymodiolus sp. Multiple species of Frenulata (Siboglinidae) are present and have a range of isotopic values that are indicative of both thiotroph- and methanotroph-based nutrition. Isotopic composition of the tubeworm Lamellibrachia sp. varied by 23.3‰ among individuals although there was no consistent difference among sites. Variation in methane use by heterotrophic fauna appears to reflect the availability of hard vs. soft substrate; macrofauna on hard substrates had high δ13C signatures, reflecting consumption of photosynthetic-derived organic matter. Two unique, biotic assemblages were discovered to be fueled largely by methane: a hard-substrate, multi-phyla sponge-associated community (inhabiting the sponge Pseudosuberites sp.) and a soft-sediment assemblage dominated by ampharetid polychaetes. Isotope signatures yield estimates of 38–100% and 6–100% methane-derived carbon in sponge associates and ampharetid-bed macrofauna, respectively. These estimates are comparable to those made for deeper methane seeps at the Florida Escarpment (3290 m) and Kodiak, Alaska seeps (4445 m). The overall high use of methane as a carbon source by both symbiont-bearing and heterotrophic fauna suggests that New Zealand methane seeps are an ideal model system to study the interaction among metazoans, bacteria, archaea, and their resulting effect on methane cycles.
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| 28. |
- Turella, Sara, et al.
(author)
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The predictive value of highly malignant EEG patterns after cardiac arrest : evaluation of the ERC-ESICM recommendations
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In: Intensive Care Medicine. - 0342-4642.
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Journal article (peer-reviewed)abstract
- Purpose: The 2021 guidelines endorsed by the European Resuscitation Council (ERC) and the European Society of Intensive Care Medicine (ESICM) recommend using highly malignant electroencephalogram (EEG) patterns (HMEP; suppression or burst-suppression) at > 24 h after cardiac arrest (CA) in combination with at least one other concordant predictor to prognosticate poor neurological outcome. We evaluated the prognostic accuracy of HMEP in a large multicentre cohort and investigated the added value of absent EEG reactivity. Methods: This is a pre-planned prognostic substudy of the Targeted Temperature Management trial 2. The presence of HMEP and background reactivity to external stimuli on EEG recorded > 24 h after CA was prospectively reported. Poor outcome was measured at 6 months and defined as a modified Rankin Scale score of 4–6. Prognostication was multimodal, and withdrawal of life-sustaining therapy (WLST) was not allowed before 96 h after CA. Results: 845 patients at 59 sites were included. Of these, 579 (69%) had poor outcome, including 304 (36%) with WLST due to poor neurological prognosis. EEG was recorded at a median of 71 h (interquartile range [IQR] 52–93) after CA. HMEP at > 24 h from CA had 50% [95% confidence interval [CI] 46–54] sensitivity and 93% [90–96] specificity to predict poor outcome. Specificity was similar (93%) in 541 patients without WLST. When HMEP were unreactive, specificity improved to 97% [94–99] (p = 0.008). Conclusion: The specificity of the ERC-ESICM-recommended EEG patterns for predicting poor outcome after CA exceeds 90% but is lower than in previous studies, suggesting that large-scale implementation may reduce their accuracy. Combining HMEP with an unreactive EEG background significantly improved specificity. As in other prognostication studies, a self-fulfilling prophecy bias may have contributed to observed results.
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| 29. |
- Wennergren, Mattias, 1993, et al.
(author)
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Swedish Child Health Services Register: a quality register for child health services and children's well-being.
- 2023
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In: BMJ paediatrics open. - : BMJ. - 2399-9772. ; 7:1
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Journal article (peer-reviewed)abstract
- Swedish child health services (CHS) is a free-of-charge healthcare system that reaches almost all children under the age of 6. The aim for the CHS is to improve children's physical, psychological and social health by promoting health and development, preventing illness and detecting emerging problems early in the child's life. The services are defined in a national programme divided into three parts: universal interventions, targeted interventions and indicated interventions.The Swedish Child Health Services Register (BHVQ) is a national Quality Register developed in 2013. The register extracts data from the child's health record and automatically presents current data in real time. At present, the register includes 21 variables.We aim to describe data available in the BHVQ and the completeness of data in BHVQ across variables.Child-specific data were exported from the register, and data for children born in the regions were retrieved from Statistics Sweden to calculate coverage.The register includes over 110000 children born between 2011 and 2022 from 221 child healthcare centres in eight of Sweden's 21 regions. In seven of the eight regions, 100% of centres report data.The completeness of data differs between participating regions and birth cohorts. The average coverage for children born in 2021 is 71%.The BHVQ is a valuable resource for evaluating Child Health Services nationally, with high coverage for the youngest children. As a result of continuous improvement of the services, the possibility to follow the development of children's health in Sweden is possible through the register. When fully expanded, the register will be a natural and essential part of developing preventive services, improving healthcare for children below 6years of age and a tool for developing evidence-based child health interventions.
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