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| 32. |
- Arctaedius, Isabelle, et al.
(författare)
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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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Ingår i: Critical Care Medicine. - 0090-3493. ; 52:4, s. 531-541
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Tidskriftsartikel (refereegranskat)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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| 33. |
- Ashton, Nicholas J., et al.
(författare)
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Alzheimer Disease Blood Biomarkers in Patients With Out-of-Hospital Cardiac Arrest
- 2023
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Ingår i: Jama Neurology. - : American Medical Association (AMA). - 2168-6149. ; 80:4, s. 388-396
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Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE Blood phosphorylated tau (p-tau) and amyloid-13 peptides (A13) are promising peripheral biomarkers of Alzheimer disease (AD) pathology. However, their potential alterations due to alternative mechanisms, such as hypoxia in patients resuscitated from cardiac arrest, are not known. OBJECTIVE To evaluate whether the levels and trajectories of blood p-tau, A1342, and A1340 following cardiac arrest, in comparison with neural injury markers neurofilament light (NfL) and total tau (t-tau), can be used for neurological prognostication following cardiac arrest.DESIGN, SETTING, AND PARTICIPANTS This prospective clinical biobank study used data from the randomized Target Temperature Management After Out-of-Hospital Cardiac Arrest (TTM) trial. Unconscious patients with cardiac arrest of presumed cardiac origin were included between November 11, 2010, and January 10, 2013, from 29 international sites. Serum analysis for serum NfL and t-tau were performed between August 1 and August 23, 2017. Serum p-tau, A1342, and A1340 were analyzed between July 1 and July 15, 2021, and between May 13 and May 25, 2022. A total of 717 participants from the TTM cohort were examined: an initial discovery subset (n = 80) and a validation subset. Both subsets were evenly distributed for good and poor neurological outcome after cardiac arrest.EXPOSURES Serum p-tau, A1342, and A1340 concentrations using single molecule array technology. Serum levels of NfL and t-tau were included as comparators.MAIN OUTCOMES AND MEASURES Blood biomarker levels at 24 hours, 48 hours, and 72 hours after cardiac arrest. Poor neurologic outcome at 6-month follow-up, defined according to the cerebral performance category scale as category 3 (severe cerebral disability), 4 (coma), or 5 (brain death).RESULTS This study included 717 participants (137 [19.1%] female and 580 male [80.9%]; mean [SD] age, 63.9 [13.5] years) who experienced out-of-hospital cardiac arrest. Significantly elevated serum p-tau levels were observed at 24 hours, 48 hours, and 72 hours in cardiac arrest patients with poor neurological outcome. The magnitude and prognostication of the change was greater at 24 hours (area under the receiver operating characteristic curve [AUC], 0.96; 95% CI, 0.95-0.97), which was similar to NfL (AUC, 0.94; 95% CI, 0.92-0.96). However, at later time points, p-tau levels decreased and were weakly associated with neurological outcome. In contrast, NfL and t-tau maintained high diagnostic accuracies, even 72 hours after cardiac arrest. Serum A1342 and A1340 concentrations increased over time in most patients but were only weakly associated with neurological outcome.CONCLUSIONS AND RELEVANCE In this case-control study, blood biomarkers indicative of AD pathology demonstrated different dynamics of change after cardiac arrest. The increase of p-tau at 24 hours after cardiac arrest suggests a rapid secretion from the interstitial fluid following hypoxic-ischemic brain injury rather than ongoing neuronal injury like NfL or t-tau. In contrast, delayed increases of A13 peptides after cardiac arrest indicate activation of amyloidogenic processing in response to ischemia.
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| 34. |
- Bascom, Karen E., et al.
(författare)
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Derivation and validation of the CREST model for very early prediction of circulatory etiology death in patients without ST-segment-elevation myocardial infarction after cardiac arrest
- 2018
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Ingår i: Circulation. - 0009-7322. ; 137:3, s. 273-282
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: No practical tool quantitates the risk of circulatory-etiology death (CED) immediately after successful cardiopulmonary resuscitation in patients without ST-segment-elevation myocardial infarction. We developed and validated a prediction model to rapidly determine that risk and facilitate triage to individualized treatment pathways. METHODS: With the use of INTCAR (International Cardiac Arrest Registry), an 87-question data set representing 44 centers in the United States and Europe, patients were classified as having had CED or a combined end point of neurological-etiology death or survival. Demographics and clinical factors were modeled in a derivation cohort, and backward stepwise logistic regression was used to identify factors independently associated with CED. We demonstrated model performance using area under the curve and the Hosmer-Lemeshow test in the derivation and validation cohorts, and assigned a simplified point-scoring system. RESULTS: Among 638 patients in the derivation cohort, 121 (18.9%) had CED. The final model included preexisting coronary artery disease (odds ratio [OR], 2.86; confidence interval [CI], 1.83-4.49; P≤0.001), nonshockable rhythm (OR, 1.75; CI, 1.10-2.77; P=0.017), initial ejection fraction<30% (OR, 2.11; CI, 1.32-3.37; P=0.002), shock at presentation (OR, 2.27; CI, 1.42-3.62; P<0.001), and ischemic time >25 minutes (OR, 1.42; CI, 0.90-2.23; P=0.13). The derivation model area under the curve was 0.73, and Hosmer-Lemeshow test P=0.47. Outcomes were similar in the 318-patient validation cohort (area under the curve 0.68, Hosmer-Lemeshow test P=0.41). When assigned a point for each associated factor in the derivation model, the average predicted versus observed probability of CED with a CREST score (coronary artery disease, initial heart rhythm, low ejection fraction, shock at the time of admission, and ischemic time >25 minutes) of 0 to 5 was: 7.1% versus 10.2%, 9.5% versus 11%, 22.5% versus 19.6%, 32.4% versus 29.6%, 38.5% versus 30%, and 55.7% versus 50%. CONCLUSIONS: The CREST model stratified patients immediately after resuscitation according to risk of a circulatory-etiology death. The tool may allow for estimation of circulatory risk and improve the triage of survivors of cardiac arrest without ST-segment-elevation myocardial infarction at the point of care.
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| 35. |
- Bentzer, Peter, et al.
(författare)
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Supersensitivity in rat micro-arteries after short-term denervation
- 1997
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Ingår i: Acta Physiologica Scandinavica. - 0001-6772. ; 161:2, s. 125-133
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Tidskriftsartikel (refereegranskat)abstract
- Contractile responses to phenylephrine and high-K+ were investigated in vitro in microvascular preparations from the rat medial plantar artery, a branch from the saphenous artery, obtained after short-term denervation in vivo. Two groups of animals were studied: (1) animals undergoing surgical resection of the saphenous nerve, and (2) animals undergoing surgical resection of both the sciatic and saphenous nerves. The animals were operated on one side only. Microvascular preparations (diameter about 325 microns) were obtained 10 days after surgery. Vessels from the non-operated side served as controls. Immunocytochemistry showed a decreased number of both neuropeptide Y (NPY) and calcitonin gene-related peptide (CGRP) immunoreactive nerve fibres in vessels after resection of the saphenous nerve only. Resection of both the saphenous and the sciatic nerve caused a complete loss of immunoreactive nerve fibres. Mechanical measurements were performed using a wire myograph. In vessels subjected to resection of the saphenous nerve the sensitivity to phenylephrine was similar to controls. Vessels denervated by resection of both the saphenous and sciatic nerves showed significant increases in phenylephrine and potassium sensitivity. When depolarized in high-K+ solution the denervated vessels showed an increased sensitivity to extracellular Ca2+. The results show that complete short-term denervation of the rat medial plantar artery in vivo causes a pronounced supersensitivity in the vascular smooth muscle. The supersensitivity appears not to be restricted to the sympathetic alpha-receptors but also associated with changes in the cellular excitation-contraction coupling. Such altered reactivity of the vascular smooth muscle may contribute to vascular disturbances observed in vivo after nerve damage or surgical denervation.
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| 36. |
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| 37. |
- Beske, Rasmus Paulin, et al.
(författare)
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The Effect of Targeted Temperature Management on the Metabolome Following Out-of-Hospital Cardiac Arrest
- 2023
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Ingår i: Therapeutic hypothermia and temperature management. - 2153-7658. ; 13:4, s. 208-215
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Tidskriftsartikel (refereegranskat)abstract
- Targeted temperature management (TTM) may moderate the injury from out-of-hospital cardiac arrest. Slowing the metabolism has been a suggested effect. Nevertheless, studies have found higher lactate levels in patients cooled to 33°C compared with 36°C even days from TTM cessation. Larger studies have not been performed on the TTM's effect on the metabolome. Accordingly, to explore the effect of TTM, we used ultra-performance liquid-mass spectrometry in a substudy of 146 patients randomized in the TTM trial to either 33°C or 36°C for 24 hours and quantified 60 circulating metabolites at the time of hospital arrival (T0) and 48 hours later (T48). From T0 to T48, profound changes to the metabolome were observed: tricarboxylic acid (TCA) cycle metabolites, amino acids, uric acid, and carnitine species all decreased. TTM significantly modified these changes in nine metabolites (Benjamini-Hochberg corrected false discovery rate <0.05): branched amino acids valine and leucine levels dropped more in the 33°C arm (change [95% confidence interval]: −60.9μM [−70.8 to −50.9] vs. −36.0μM [−45.8 to −26.3] and −35.5μM [−43.1 to −27.8] vs. −21.2μM [−28.7 to −13.6], respectively), whereas the TCA metabolites including malic acid and 2-oxoglutaric acid remained higher for the first 48 hours (−7.7μM [−9.7 to −5.7] vs. −10.4μM [−12.4 to −8.4] and −3μM [−4.3 to −1.7] vs. −3.7μM [−5 to −2.3]). Prostaglandin E2 only dropped in the TTM 36°C group. The results show that TTM affects the metabolism hours after normothermia have been reached.
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| 38. |
- Bjørnsbo, Kirsten Schroll, et al.
(författare)
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Protocol for the combined cardiometabolic deep phenotyping and registry-based 20-year follow-up study of the Inter99 cohort
- 2024
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Ingår i: BMJ Open. - 2044-6055. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- Introduction The population-based Inter99 cohort has contributed extensively to our understanding of effects of a systematic screening and lifestyle intervention, as well as the multifactorial aetiology of type 2 diabetes (T2D) and cardiovascular disease. To understand causes, trajectories and patterns of early and overt cardiometabolic disease manifestations, we will perform a combined clinical deep phenotyping and registry follow-up study of the now 50–80 years old Inter99 participants. Methods and analysis The Inter99 cohort comprises individuals aged 30–60 years, who lived in a representative geographical area of greater Copenhagen, Denmark, in 1999. Age-stratified and sex-stratified random subgroups were invited to participate in either a lifestyle intervention (N=13 016) or questionnaires (N=5264), while the rest served as a reference population (N=43 021). Of the 13 016 individuals assigned to the lifestyle intervention group, 6784 (52%) accepted participation in a baseline health examination in 1999, including screening for cardiovascular risk factors and prediabetic conditions. In total, 6004 eligible participants, who participated in the baseline examination, will be invited to participate in the deep phenotyping 20-year follow-up clinical examination including measurements of anthropometry, blood pressure, arterial stiffness, cardiometabolic biomarkers, coronary artery calcification, heart rate variability, heart rhythm, liver stiffness, fundus characteristics, muscle strength and mass, as well as health and lifestyle questionnaires. In a subsample, 10-day monitoring of diet, physical activity and continuous glucose measurements will be performed. Fasting blood, urine and faecal samples to be stored in a biobank. The established database will form the basis of multiple analyses. A main purpose is to investigate whether low birth weight independent of genetics, lifestyle and glucose tolerance predicts later common T2D cardiometabolic comorbidities. Ethics and dissemination The study was approved by the Medical Ethics Committee, Capital Region, Denmark (H-20076231) and by the Danish Data Protection Agency through the Capital Region of Denmark’s registration system (P-2020-1074). Informed consent will be obtained before examinations. Findings will be disseminated in peer-reviewed journals, at conferences and via presentations to stakeholders, including patients and public health policymakers.
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