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  • Elfwén, Ludvig, et al. (författare)
  • Direct or subacute coronary angiography in out-of-hospital cardiac arrest (DISCO)—An initial pilot-study of a randomized clinical trial
  • 2019
  • Ingår i: Resuscitation. - Elsevier. - 0300-9572. ; 139, s. 253-261
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The clinical importance of immediate coronary angiography, with potentially subsequent percutaneous coronary intervention (PCI), in out-of-hospital cardiac arrest (OHCA) patients without ST-elevation on the ECG is unclear. In this study, we assessed feasibility and safety aspects of performing immediate coronary angiography in a pre-specified pilot phase of the ‘DIrect or Subacute Coronary angiography in Out-of-hospital cardiac arrest’ (DISCO) randomized controlled trial (ClinicalTrials.gov ID: NCT02309151). Methods: Resuscitated bystander witnessed OHCA patients >18 years without ST-elevation on the ECG were randomized to immediate coronary angiography versus standard of care. Event times, procedure related adverse events and safety variables within 7 days were recorded. Results: In total, 79 patients were randomized to immediate angiography (n = 39) or standard of care (n = 40). No major differences in baseline characteristics between the groups were found. There were no differences in the proportion of bleedings and renal failure. Three patients randomized to immediate angiography and six patients randomized to standard care died within 24 h. The median time from EMS arrival to coronary angiography was 135 min in the immediate angiography group. In patients randomized to immediate angiography a culprit lesion was found in 14/38 (36.8%) and PCI was performed in all these patients. In 6/40 (15%) patients randomized to standard of care, coronary angiography was performed before the stipulated 3 days. Conclusion: In this out-of-hospital cardiac arrest population without ST-elevation, randomization to a strategy to perform immediate coronary angiography was feasible although the time window of 120 min from EMS arrival at the scene of the arrest to start of coronary angiography was not achieved. No significant safety issues were reported.
  • Lagedal, Rickard, et al. (författare)
  • Design of DISCO—Direct or Subacute Coronary Angiography in Out-of-Hospital Cardiac Arrest study
  • 2018
  • Ingår i: American Heart Journal. - Mosby. - 0002-8703. ; 197, s. 53-61
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Acute coronary syndrome is a common cause of out-of-hospital cardiac arrest (OHCA). In patients with OHCA presenting with ST elevation, immediate coronary angiography and potential percutaneous coronary intervention (PCI) after return of spontaneous circulation are recommended. However, the evidence for this invasive strategy in patients without ST elevation is limited. Observational studies have shown a culprit coronary artery occlusion in about 30% of these patients, indicating the electrocardiogram's (ECG's) limited sensitivity. The aim of this study is to determine whether immediate coronary angiography and subsequent PCI will provide outcome benefits in OHCA patients without ST elevation. Methods/design We describe the design of the DIrect or Subacute Coronary angiography in Out-of-hospital cardiac arrest study (DISCO)—a pragmatic national, multicenter, randomized, clinical study. OHCA patients presenting with no ST elevation on their first recorded ECG will be randomized to a strategy of immediate coronary angiography or to standard of care with admission to intensive care and angiography after 3 days at the earliest unless the patient shows signs of acute ischemia or hemodynamic instability. Primary end point is 30-day survival. An estimated 1,006 patients give 80% power (α =.05) to detect a 20% improved 30-day survival rate from 45% to 54%. Secondary outcomes include good neurologic recovery at 30 days and 6 months, and cognitive function and cardiac function at 6 months. Conclusion This randomized clinical study will evaluate the effect of immediate coronary angiography after OHCA on 30-day survival in patients without ST elevation on their first recorded ECG.
  • Lehmann-Werman, Roni, et al. (författare)
  • Identification of tissue-specific cell death using methylation patterns of circulating DNA.
  • 2016
  • Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - 1091-6490. ; 113:13, s. E1826-34
  • Tidskriftsartikel (refereegranskat)abstract
    • Minimally invasive detection of cell death could prove an invaluable resource in many physiologic and pathologic situations. Cell-free circulating DNA (cfDNA) released from dying cells is emerging as a diagnostic tool for monitoring cancer dynamics and graft failure. However, existing methods rely on differences in DNA sequences in source tissues, so that cell death cannot be identified in tissues with a normal genome. We developed a method of detecting tissue-specific cell death in humans based on tissue-specific methylation patterns in cfDNA. We interrogated tissue-specific methylome databases to identify cell type-specific DNA methylation signatures and developed a method to detect these signatures in mixed DNA samples. We isolated cfDNA from plasma or serum of donors, treated the cfDNA with bisulfite, PCR-amplified the cfDNA, and sequenced it to quantify cfDNA carrying the methylation markers of the cell type of interest. Pancreatic β-cell DNA was identified in the circulation of patients with recently diagnosed type-1 diabetes and islet-graft recipients; oligodendrocyte DNA was identified in patients with relapsing multiple sclerosis; neuronal/glial DNA was identified in patients after traumatic brain injury or cardiac arrest; and exocrine pancreas DNA was identified in patients with pancreatic cancer or pancreatitis. This proof-of-concept study demonstrates that the tissue origins of cfDNA and thus the rate of death of specific cell types can be determined in humans. The approach can be adapted to identify cfDNA derived from any cell type in the body, offering a minimally invasive window for diagnosing and monitoring a broad spectrum of human pathologies as well as providing a better understanding of normal tissue dynamics.
  • Arakelian, Erebouni, et al. (författare)
  • Pulmonary influences on early post-operative recovery in patients after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy treatment a retrospective study
  • 2012
  • Ingår i: World Journal of Surgical Oncology. - 1477-7819 .- 1477-7819. ; 10, s. 258
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>Background: The combination of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is a curative treatment option for peritoneal carcinomatosis (PC). There have been few studies on the pulmonary adverse events (AEs) affecting patient recovery after this treatment, thus this study investigated these factors. Methods: Between January 2005 and December 2006, clinical data on all pulmonary AEs and the recovery progress were reviewed for 76 patients with after CRS and HIPEC. Patients with pulmonary interventions (thoracocenthesis and chest tubes) were compared with the non-intervention patients. Two senior radiologists, blinded to the post-operative clinical course, separately graded the occurrence of pulmonary AEs. Results: Of the 76 patients, 6 had needed thoracocentesis and another 6 needed chest tubes. There were no differences in post-operative recovery between the intervention and non-intervention groups. The total number of days on mechanical ventilation, the length of stay in the intensive care unit, total length of hospital stay, tumor burden, and an American Society of Anesthesiologists (ASA) grade of greater than 2 were correlated with the occurrence of atelectasis and pleural effusion. Extensive atelectasis (grade 3 or higher) was seen in six patients, major pleural effusion (grade 3) in seven patients, and signs of heart failure (grade 1-2) in nine patients. Conclusions: Clinical and radiological post-operative pulmonary AEs are common after CRS and HIPEC. However, most of the pulmonary AEs did not affect post-operative recovery.</p>
  • Basu, Samar, et al. (författare)
  • Development of a novel biomarker of free radical damage in reperfusion injury after cardiac arrest
  • 2000
  • Ingår i: FEBS Letters. - 0014-5793 .- 1873-3468. ; 470:1, s. 1-6
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>In a porcine model of cardiopulmonary resuscitation (CPR), we investigated changes in the plasma levels of 8-iso-PGF(2alpha), a marker for oxidative injury, and 15-keto-dihydro-PGF(2alpha), an inflammatory response indicator during the post-resuscitation period after cardiac arrest. Twelve piglets were subjected to either 2 or 5 min (VF2 and VF5 group) of ventricular fibrillation (VF) followed by 5 min of closed-chest CPR. Six piglets without cardiac arrest were used as controls. In VF5 group, 8-iso-PGF(2alpha) in the jugular bulb plasma (draining the brain) increased four-fold. Jugular bulb 8-iso-PGF(2alpha) in the control group remained unchanged. The 15-keto-dihydro-PGF(2alpha) also increased four-fold in the VF5 group. Thus, 8-iso-PGF(2alpha) and 15-keto-dihydro-PGF(2alpha) measurements in jugular bulb plasma may be used as biomarkers for quantification of free radical catalyzed oxidative brain injury and inflammatory response in reperfusion injury</p>
  • Basu, Samar, et al. (författare)
  • Evidence for Time-dependent Maximum Increase ofFree Radical Damage and Eicosanoid Formation in theBrain as Related to Duration of Cardiac Arrest andCardio-pulmonary Resuscitation
  • 2003
  • Ingår i: Free radical research. - 1071-5762 .- 1029-2470. ; 37:3, s. 251-256
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>Recovery of neurological function in patients following cardiac arrest and cardiopulmonary resuscitation (CPR) is a complex event. Free radical induced oxidative stress is supposed to be involved in this process. We studied levels of 8-iso-PGF2alpha (indicating oxidative injury) and 15-keto-dihydro-PGF2alpha (indicating inflammatory response) in venous plasma obtained from the jugular bulb in a porcine model of experimental cardiopulmonary resuscitation (CPR) where 2, 5, 8, 10 or 12 min of ventricular fibrillation (VF) was followed by 5 or 8 min of closed-chest CPR. A significant increase of 8-iso-PGF2alpha was observed immediately following restoration of spontaneous circulation in all experiments of various duration of VF and CPR. No such increase was seen in a control group. When compared between the groups there was a duration-dependent maximum increase of 8-iso-PGF2alpha which was greatest in animals subjected to the longest period (VF12 min + CPR8 min) of no or low blood flow. In contrast, the greatest increase of 15-keto-dihydro-PGF2alpha was observed in the 13 min group (VF8 min + CPR5 min). Thus, a time-dependent cerebral oxidative injury occurs in conjunction which cardiac arrest and CPR.</p>
  • Bullock, A, et al. (författare)
  • International standards for programmes of training in intensive care medicine in Europe
  • 2011
  • Ingår i: Intensive Care Medicine. - 0342-4642 .- 1432-1238. ; 37:3, s. 385-393
  • Tidskriftsartikel (refereegranskat)abstract
    • <p><strong>PURPOSE:</strong></p><p>To develop internationally harmonised standards for programmes of training in intensive care medicine (ICM).</p><p><strong>METHODS:</strong></p><p>Standards were developed by using consensus techniques. A nine-member nominal group of European intensive care experts developed a preliminary set of standards. These were revised and refined through a modified Delphi process involving 28 European national coordinators representing national training organisations using a combination of moderated discussion meetings, email, and a Web-based tool for determining the level of agreement with each proposed standard, and whether the standard could be achieved in the respondent's country.</p><p><strong>RESULTS:</strong></p><p>The nominal group developed an initial set of 52 possible standards which underwent four iterations to achieve maximal consensus. All national coordinators approved a final set of 29 standards in four domains: training centres, training programmes, selection of trainees, and trainers' profiles. Only three standards were considered immediately achievable by all countries, demonstrating a willingness to aspire to quality rather than merely setting a minimum level. Nine proposed standards which did not achieve full consensus were identified as potential candidates for future review.</p><p><strong>CONCLUSIONS:</strong></p><p>This preliminary set of clearly defined and agreed standards provides a transparent framework for assuring the quality of training programmes, and a foundation for international harmonisation and quality improvement of training in ICM.</p>
  • Carlsson, Markus, et al. (författare)
  • Inflammatory and circulatory effects of the reduction of endotoxin concentration in established porcine endotoxemic shock : a model of endotoxin elimination
  • 2009
  • Ingår i: Critical Care Medicine. - 0090-3493 .- 1530-0293. ; 37:3, s. 1031-e4
  • Tidskriftsartikel (refereegranskat)abstract
    • <p><strong>Objective:</strong></p><p>To study whether a reduction of the endotoxin load, once a generalized inflammatory state has been established, reduces the inflammatory response and endotoxin-induced effects on circulation, hypoperfusion, and organ dysfunction.</p><p><strong>Design:</strong></p><p>Prospective parallel-grouped placebo-controlled randomized interventional experimental study.</p><p><strong>Setting:</strong></p><p>University research unit.</p><p><strong>Subjects: </strong></p><p>Healthy pigs.</p><p><strong>Interventions:</strong></p><p>The animals were subjected to a continuous endotoxin infusion rate of either 4.0 or 0.063 µg endotoxin × kg<sup>-1</sup> × h<sup>-1</sup> for 1, 2, or 6 hours. The 1- and 2-hour infusion groups represented the applied therapy by a reduction of the endotoxin load of 5/6 and 2/3, respectively.</p><p><strong>Measurements and Main Results:</strong></p><p>During a 6-hour experiment, laboratory and physiologic parameters were recorded hourly in 26 anesthetized and mechanically ventilated pigs. Primary end point was to detect differences in tumor necrosis factor-[alpha] (TNF-[alpha]) concentration during the last 3 hours of the experiment. Despite the early reduction of the endotoxin load, no effect on TNF-[alpha] concentration was observed. Similarly, in circulatory parameters, such as mean arterial pressure and oxygen delivery, and in platelet count and renal function, no effects were noted. However, there was some improvement in pulmonary compliance and function as determined by Pao<sub>2</sub>, Paco<sub>2</sub>, and pH. These changes were associated with slight improvements in leukocyte response and capillary leakage.</p><p><strong>Conclusions:</strong></p><p>Termination of the endotoxin infusion represents an incontestable model of endotoxin concentration reduction. Endotoxin elimination strategies applied at the TNF-[alpha] peak or later will have very little or no effect on TNF-[alpha]–mediated toxicity. Nevertheless, there was an effect on the leukocyte response that was associated with an improvement in respiratory function and microcirculation, making it impossible to rule out fully the beneficial effect of this strategy. However, the effects were limited in relation to the magnitude of the endotoxin concentration reduction and the very early application of the antiendotoxin measure.</p>
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