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The potential benefit of early coronary angiography in out-of-hospital cardiac arrest (OHCA) patients without ST elevation on ECG is unclear. The aim of this study was to evaluate the association between early coronary angiography and survival in these patients. Nationwide observational study between 2008 and 2013. Included were patients admitted to hospital after witnessed OHCA, with shockable rhythm, age 18 to 80 years and unconscious. Patients with ST-elevation on ECG were excluded. Patients that underwent early CAG (within 24 hours) were compared with no early CAG (later during the hospital stay or not at all). Outcomes were survival at 30 days, 1 year, and 3 years. Multivariate analysis included pre-hospital factors, comorbidity and ECG-findings. In total, 799 OHCA patients fulfilled the inclusion criteria, of which 275 (34%) received early CAG versus 524 (66%) with no early CAG. In the early CAG group, the proportion of patients with an occluded coronary artery was 27% and 70% had at least one significant coronary stenosis (defined as narrowing of coronary lumen diameter of ≥50%). The 30-day survival rate was 65% in early CAG group versus 52% with no early CAG (P < .001). The adjusted OR was 1.42 (95% CI 1.00-2.02). The one-year survival rate was 62% in the early CAG group versus 48% in the no early CAG group with the adjusted hazard ratio of 1.35 (95% CI 1.04-1.77). In this population of bystander-witnessed cases of out-of-hospital cardiac arrest with shockable rhythm and ECG without ST elevation, early coronary angiography may be associated with improved short and long term survival.

Introduction Previous studies have suggested an effect of gender on outcome after out-of-hospital cardiac arrest (OHCA), but the results are conflicting. We aimed to investigate the association of gender to outcome, coronary angiography (CAG) and adverse events in OHCA survivors treated with mild induced hypothermia (MIH). Methods We performed a retrospective analysis of prospectively collected data from the International Cardiac Arrest Registry. Adult patients with a non-traumatic OHCA and treated with MIH were included. Good neurological outcome was defined as a cerebral performance category (CPC) of 1 or 2. Results A total of 1,667 patients, 472 women (28%) and 1,195 men (72%), met the inclusion criteria. Men were more likely to receive bystander cardiopulmonary resuscitation, have an initial shockable rhythm and to have a presumed cardiac cause of arrest. At hospital discharge, men had a higher survival rate (52% vs. 38%, P <0.001) and more often a good neurological outcome (43% vs. 32%, P <0.001) in the univariate analysis. When adjusting for baseline characteristics, male gender was associated with improved survival (OR 1.34, 95% CI 1.01 to 1.78) but no longer with neurological outcome (OR 1.24, 95% CI 0.92 to 1.67). Adverse events were common; women more often had hypokalemia, hypomagnesemia and bleeding requiring transfusion, while men had more pneumonia. In a subgroup analysis of patients with a presumed cardiac cause of arrest (n = 1,361), men more often had CAG performed on admission (58% vs. 50%, P  = 0.02) but this discrepancy disappeared in an adjusted analysis. Conclusions Gender differences exist regarding cause of arrest, adverse events and outcome. Male gender was independently associated with survival but not with neurological outcome.

Background The COVID-19 pandemic, which has a prominent social and economic impact worldwide, shows a largely unexplained male bias for the severity and mortality of the disease. Loss of chromosome Y (LOY) is a risk factor candidate in COVID-19 due to its prior association with many chronic age-related diseases, and its impact on immune gene transcription. Methods Publicly available scRNA-seq data of PBMC samples derived from male patients critically ill with COVID-19 were reanalyzed, and LOY status was added to the annotated cells. We further studied LOY in whole blood for 211 COVID-19 patients treated at intensive care units (ICU) from the first and second waves of the pandemic. Of these, 139 patients were subject to cell sorting for LOY analysis in granulocytes, low-density neutrophils (LDNs), monocytes, and PBMCs. Results Reanalysis of available scRNA-seq data revealed LDNs and monocytes as the cell types most affected by LOY. Subsequently, DNA analysis indicated that 46%, 32%, and 29% of critically ill patients showed LOY above 5% cut-off in LDNs, granulocytes, and monocytes, respectively. Hence, the myeloid lineage that is crucial for the development of severe COVID-19 phenotype is affected by LOY. Moreover, LOY correlated with increasing WHO score (median difference 1.59%, 95% HDI 0.46% to 2.71%, p =0.025), death during ICU treatment (median difference 1.46%, 95% HDI 0.47% to 2.43%, p =0.0036), and history of vessel disease (median difference 2.16%, 95% HDI 0.74% to 3.7%, p =0.004), among other variables. In 16 recovered patients, sampled during ICU stay and 93–143 days later, LOY decreased significantly in whole blood and PBMCs. Furthermore, the number of LDNs at the recovery stage decreased dramatically (median difference 76.4 per 10,000 cell sorting events, 95% HDI 55.5 to 104, p =6e−11). Conclusions We present a link between LOY and an acute, life-threatening infectious disease. Furthermore, this study highlights LOY as the most prominent clonal mutation affecting the myeloid cell lineage during emergency myelopoiesis. The correlation between LOY level and COVID-19 severity might suggest that this mutation affects the functions of monocytes and neutrophils, which could have consequences for male innate immunity.

Amyloid β (Aβ) peptides are proteolytic products from amyloid precursor protein (APP) and are thought to play a role in Alzheimer disease (AD) pathogenesis. While much is known about molecular mechanisms underlying cerebral Aβ accumulation in familial AD, less is known about the cause(s) of brain amyloidosis in sporadic disease. Animal and postmortem studies suggest that Aβ secretion can be up-regulated in response to hypoxia. We employed a new technology (Single Molecule Arrays, SiMoA) capable of ultrasensitive protein measurements and developed a novel assay to look for changes in serum Aβ42 concentration in 25 resuscitated patients with severe hypoxia due to cardiac arrest. After a lag period of 10 or more hours, very clear serum Aβ42 elevations were observed in all patients. Elevations ranged from approximately 80% to over 70-fold, with most elevations in the range of 3-10-fold (average approximately 7-fold). The magnitude of the increase correlated with clinical outcome. These data provide the first direct evidence in living humans that ischemia acutely increases Aβ levels in blood. The results point to the possibility that hypoxia may play a role in the amyloidogenic process of AD.

BackgroundVentilation during cardiopulmonary resuscitation (CPR) has long been a part of the standard treatment during cardiac arrests. Ventilation is usually given either during continuous chest compressions (CCC) or during a short pause after every 30 chest compressions (30:2). There is limited knowledge of how ventilation is delivered if it effects the hemodynamics and if it plays a role in the occurrence of lung injuries. The aim of this study was to compare ventilation parameters, hemodynamics, blood gases and lung injuries during experimental CPR given with CCC and 30:2 in a porcine model.MethodsSixteen pigs weighing approximately 33 kg were randomized to either receive CPR with CCC or 30:2. Ventricular fibrillation was induced by passing an electrical current through the heart. CPR was started after 3 min and given for 20 min. Chest compressions were provided mechanically with a chest compression device and ventilations were delivered manually with a self-inflating bag and 12 l/min of oxygen. During the experiment, ventilation parameters and hemodynamics were sampled continuously, and arterial blood gases were taken every five minutes. After euthanasia and cessation of CPR, the lungs and heart were removed in block and visually examined followed by sampling of lung tissue which were examined using microscopy.ResultsIn the CCC group and the 30:2 group, peak inspiratory pressure (PIP) was 58.6 and 35.1 cmH2O (p < 0.001), minute volume (MV) 2189.6 and 1267.1 ml (p < 0.001), peak expired carbon dioxide (PECO2) 28.6 and 39.4 mmHg (p = 0.020), partial pressure of carbon dioxide (PaCO2) 50.2 and 61.1 mmHg (p = 0.013) and pH 7.3 and 7.2 (p = 0.029), respectively. Central venous pressure (CVP) decreased more over time in the 30:2 group (p = 0.023). All lungs were injured, but there were no differences between the groups.ConclusionsVentilation during CCC resulted in a higher PIP, MV and pH and lower PECO2 and PaCO2, showing that ventilation mode during CPR can affect ventilation parameters and blood gases.

Background: Standard dosages of analgesic and sedative drugs are given to intensive care patients. The resulting range of blood concentrations and corresponding clinical responses need to be better examined. The purpose of this study was to describe daily dosages, measured blood concentrations, and clinical responses in critically ill patients. The purpose was also to contribute to establishing whole blood concentration reference values of the drugs investigated. Methods: A descriptive study of prospectively collected data from 302 admissions to a general intensive care unit (ICU) at a university hospital. Ten drugs (clonidine, fentanyl, morphine, dexmedetomidine, ketamine, ketobemidone, midazolam, paracetamol, propofol, and thiopental) were investigated, and daily dosages recorded. Blood samples were collected twice daily, and drug concentrations were measured. Clinical responses were registered using Richmond agitation-sedation scale (RASS) and Numeric rating scale (NRS). Results: Drug dosages were within recommended dose ranges. Blood concentrations for all 10 drugs showed a wide variation within the cohort, but only 3% were above therapeutic interval where clonidine (57 of 122) and midazolam (38 of 122) dominated. RASS and NRS were not correlated to drug concentrations. Conclusion: Using recommended dose intervals for analgesic and sedative drugs in the ICU setting combined with regular monitoring of clinical responses such as RASS and NRS leads to 97% of concentrations being below the upper limit in the therapeutic interval. This study contributes to whole blood drug concentration reference values regarding these 10 drugs.

Introduction Laparoscopic liver surgery is evolving and the best technique for dividing the liver parenchyma is currently under debate. The aim of this study was to study different techniques during a full laparoscopic lobe resection, and determine the efficacy and risks of bleeding and gas embolism. Methods Sixteen pigs were randomized to two groups: group US underwent an operation with Ultracision shears (AutoSonix) and ultrasonic dissector (CUSA) and group VS with a vessel sealing system (Ligasure) and ultrasonic dissector. A left lobe resection was performed. Transesophageal endoscopic echocardiography (TEE) was used to detect gas emboli in the right side of the heart and pulmonary artery. The operations and TEE were recorded for later assessment. Results Compared with group VS, group US exhibited significantly more intraoperative bleeding ( p  = 0.02), a trend towards a longer operation time ( p  = 0.08), and a trend towards more embolization for grade I emboli. In total, 10 of 15 animals had emboli during the operation. Conclusions This study showed that a laparoscopic left lobe resection can be performed with a combination of AutoSonix and CUSA as well as with Ligasure and CUSA instrumentation. In our hands, less bleeding was incurred with Ligasure than with AutoSonix.

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 amethod 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.

Background The LUCAS™ device delivers mechanical chest compressions that have been shown in experimental studies to improve perfusion pressures to the brain and heart as well as augmenting cerebral blood flow and end tidal CO 2, compared with results from standard manual cardiopulmonary resuscitation (CPR). Two randomised pilot studies in out-of-hospital cardiac arrest patients have not shown improved outcome when compared with manual CPR. There remains evidence from small case series that the device can be potentially beneficial compared with manual chest compressions in specific situations. This multicentre study is designed to evaluate the efficacy and safety of mechanical chest compressions with the LUCAS™ device whilst allowing defibrillation during on-going CPR, and comparing the results with those of conventional resuscitation. Methods/design This article describes the design and protocol of the LINC-study which is a randomised controlled multicentre study of 2500 out-of-hospital cardiac arrest patients. The study has been registered at ClinicalTrials.gov ( http://clinicaltrials.gov/ct2/show/NCT00609778?term=LINC&rank=1 ). Results Primary endpoint is four-hour survival after successful restoration of spontaneous circulation. The safety aspect is being evaluated by post mortem examinations in 300 patients that may reflect injuries from CPR. Conclusion This large multicentre study will contribute to the evaluation of mechanical chest compression in CPR and specifically to the efficacy and safety of the LUCAS™ device when used in association with defibrillation during on-going CPR.

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.