The leading cause of morbidity and mortality after surviving the rupture of an intracranial aneurysm is delayed cerebral ischaemia (DCI). We present an update of recent literature on the current ...status of prevention and treatment strategies for DCI after aneurysmal subarachnoid haemorrhage. A systematic literature search of three databases (PubMed, ISI Web of Science, and Embase) was performed. Human clinical trials assessing treatment strategies, published in the last 5 yr, were included based on full-text analysis. Study data were extracted using tables depicting study type, sample size, and outcome variables. We identified 49 studies meeting our inclusion criteria. Clazosentan, magnesium, and simvastatin have been tested in large high-quality trials but failed to show a beneficial effect. Cilostazol, eicosapentaenoic acid, erythropoietin, heparin, and methylprednisolone yield promising results in smaller, non-randomized or retrospective studies and warrant further investigation. Topical application of nicardipine via implants after clipping has been shown to reduce clinical and angiographic vasospasm. Methods to improve subarachnoid blood clearance have been established, but their effect on outcome remains unclear. Haemodynamic management of DCI is evolving towards euvolaemic hypertension. Endovascular rescue therapies, such as percutaneous transluminal balloon angioplasty and intra-arterial spasmolysis, are able to resolve angiographic vasospasm, but their effect on outcome needs to be proved. Many novel therapies for preventing and treating DCI after aneurysmal subarachnoid haemorrhage have been assessed, with variable results. Limitations of the study designs often preclude definite statements. Current evidence does not support prophylactic use of clazosentan, magnesium, or simvastatin. Many strategies remain to be tested in larger randomized controlled trials.
This systematic review was registered in the international prospective register of systematic reviews. PROSPERO: CRD42015019817.
Clinical manifestations of COVID-19 affect many organs, including the heart. Cardiovascular disease is a dominant comorbidity and prognostic factors predicting risk for critical courses are highly ...needed. Moreover, immunomechanisms underlying COVID-induced myocardial damage are poorly understood.
To elucidate prognostic markers to identify patients at risk.
Only patients with pericardial effusion (PE) developed a severe disease course, and those who died could be identified by a high CD8/Treg/monocyte ratio. Ten out of 19 COVID-19 patients presented with PE, 7 (78%) of these had elevated APACHE-II mortality risk-score, requiring mechanical ventilation. At admission, PE patients showed signs of systemic and cardiac inflammation in NMR and impaired cardiac function as detected by transthoracic echocardiography (TTE), whereas parameters of myocardial injury e.g. high sensitive troponin-t (hs-TnT) were not yet increased. During the course of disease, hs-TnT rose in 8 of the PE-patients above 16 ng/l, 7 had to undergo ventilatory therapy and 4 of them died. FACS at admission showed in PE patients elevated frequencies of CD3+CD8+ T cells among all CD3+ T-cells, and lower frequencies of Tregs and CD14+HLA−DR+-monocytes. A high CD8/Treg/monocyte ratio predicted a severe disease course in PE patients, and was associated with high serum levels of antiviral cytokines. By contrast, patients without PE and PE patients with a low CD8/Treg/monocyte ratio neither had to be intubated, nor died.
PE predicts cardiac injury in COVID-19 patients. Therefore, TTE should be performed at admission. Immunological parameters for dysfunctional antiviral immunity, such as the CD8/Treg/monocyte ratio used here, supports risk assessment by predicting poor prognosis.
Clear cell renal cell carcinoma (ccRCC) is the most common kidney cancer and is often caused by mutations in the oxygen-sensing machinery of kidney epithelial cells. Due to its pseudo-hypoxic state, ...ccRCC recruits extensive vasculature and other stromal components. Conventional cell culture methods provide poor representation of stromal cell types in primary cultures of ccRCC, and we hypothesized that mimicking the extracellular environment of the tumor would promote growth of both tumor and stromal cells. We employed proteomics to identify the components of ccRCC extracellular matrix (ECM) and found that in contrast to healthy kidney cortex, laminin, collagen IV, and entactin/nidogen are minor contributors. Instead, the ccRCC ECM is composed largely of collagen VI, fibronectin, and tenascin C. Analysis of single cell expression data indicates that cancer-associated fibroblasts are a major source of tumor ECM production. Tumor cells as well as stromal cells bind efficiently to a nine-component ECM blend characteristic of ccRCC. Primary patient-derived tumor cells bind the nine-component blend efficiently, allowing to us to establish mixed primary cultures of tumor cells and stromal cells. These miniature patient-specific replicas are conducive to microscopy and can be used to analyze interactions between cells in a model tumor microenvironment.
Porous silk protein scaffolds are designed to display shape memory characteristics and volumetric recovery following compression. Two strategies are utilized to realize shape recovery: addition of ...hygroscopic plasticizers like glycerol, and tyrosine modifications with hydrophilic sulfonic acid chemistries. Silk sponges are evaluated for recovery following 80% compressive strain, total porosity, pore size distribution, secondary structure development, in vivo volume retention, cell infiltration, and inflammatory responses. Glycerol‐modified sponges recover up to 98.3% of their original dimensions following compression, while sulfonic acid/glycerol modified sponges swell in water up to 71 times their compressed volume, well in excess of their original size. Longer silk extraction times (lower silk molecular weights) and higher glycerol concentrations yielded greater flexibility and shape fidelity, with no loss in modulus following compression. Sponges are over 95% porous, with secondary structure analysis indicating glycerol‐induced β‐sheet physical crosslinking. Tyrosine modifications with sulfonic acid interfere with β‐sheet formation. Glycerol‐modified sponges exhibit improved rates of cellular infiltration at subcutaneous implant sites with minimal immune response in mice. They also degrade more rapidly than unmodified sponges, a result posited to be cell‐mediated. Overall, this work suggests that silk sponges may be useful for minimally invasive deployment in soft tissue augmentation procedures.
Silk protein sponges show enhanced shape memory properties and elasticity when modified with hydrophilic plasticizers, making them ideal for minimally invasive deployment in soft tissue augmentation procedures.
Arterial pressure waveform analysis of cardiac output (APCO) without external calibration (FloTrac/Vigileo™) is critically dependent upon computation of vascular tone that has necessitated several ...refinements of the underlying software algorithms. We hypothesized that changes in vascular tone induced by high-dose vasopressor therapy affect the accuracy of APCO measurements independently of the FloTrac software version.
In this prospective observational study, we assessed the validity of uncalibrated APCO measurements compared with transpulmonary thermodilution cardiac output (TPCO) measurements in 24 patients undergoing vasopressor therapy for the treatment of cerebral vasospasm after subarachnoid haemorrhage.
Patients received vasoactive support with mean (sd) 0.53 (0.46) µg kg−1 min−1 norepinephrine resulting in mean arterial pressure of 104 (14) mm Hg and mean systemic vascular resistance of 943 (248) dyn s−1 cm−5. Cardiac output (CO) data pairs (158) were obtained simultaneously by APCO and TPCO measurements. TPCO ranged from 5.2 to 14.3 litre min−1, and APCO from 4.1 to 13.7 litre min−1. Bias and limits of agreement were 0.9 and 2.5 litre min−1, resulting in an overall percentage error of 29.6% for 68 data pairs analysed with the second-generation FloTrac® software and 27.9% for 90 data pairs analysed with the third-generation software. Precision of the reference technique was 2.6%, while APCO measurements yielded a precision of 29.5% and 27.9% for the second- and the third-generation software, respectively. For both software versions, bias (TPCO–APCO) correlated inversely with systemic vascular resistance.
In neurosurgical patients requiring high-dose vasopressor support, precision of uncalibrated CO measurements depended on systemic vascular resistance. Introduction of the third software algorithm did not improve the insufficient precision (>20%) for APCO measurements observed with the second software version.
A tele-emergency medical service with a remote emergency physician for severe prehospital emergencies may overcome the increasing number of emergency calls and shortage of emergency medical service ...providers. We analysed whether routine use of a tele-emergency medical service is non-inferior to a conventional physician-based one in the occurrence of intervention-related adverse events.
This open-label, randomised, controlled, parallel-group, non-inferiority trial included all routine severe emergency patients aged ≥ 18 years within the ground-based ambulance service of Aachen, Germany. Patients were randomised in a 1:1 allocation ratio to receive either tele-emergency medical service (n = 1764) or conventional physician-based emergency medical service (n = 1767). The primary outcome was the occurrence of intervention-related adverse events with suspected causality to the group assignment. The trial was registered with ClinicalTrials.gov (NCT02617875) on 30 November 2015 and is reported in accordance with the CONSORT statement for non-inferiority trials.
Among 3531 randomised patients, 3220 were included in the primary analysis (mean age, 61.3 years; 53.8% female); 1676 were randomised to the conventional physician-based emergency medical service (control) group and 1544 to the tele-emergency medical service group. A physician was not deemed necessary in 108 of 1676 cases (6.4%) and 893 of 1544 cases (57.8%) in the control and tele-emergency medical service groups, respectively. The primary endpoint occurred only once in the tele-emergency medical service group. The Newcombe hybrid score method confirmed the non-inferiority of the tele-emergency medical service, as the non-inferiority margin of - 0.015 was not covered by the 97.5% confidence interval of - 0.0046 to 0.0025.
Among severe emergency cases, tele-emergency medical service was non-inferior to conventional physician-based emergency medical service in terms of the occurrence of adverse events.
Off-pump coronary artery bypass (OPCAB) surgery carries a high risk for haemodynamic instability and perioperative organ injury. Favourable haemodynamic effects and organ-protective properties could ...render xenon an attractive anaesthetic for OPCAB surgery. The primary aim of this study was to assess whether xenon anaesthesia for OPCAB surgery is non-inferior to sevoflurane anaesthesia with regard to intraoperative vasopressor requirements.
Forty-two patients undergoing elective OPCAB surgery were enrolled in this prospective, single-blind, randomized controlled pilot trial. Patients were randomized to either xenon (50–60 vol%) or sevoflurane (1.1–1.4 vol%) anaesthesia. Primary outcome was intraoperative noradrenaline requirements necessary to achieve predefined haemodynamic goals. Secondary outcomes included safety variables such as the occurrence of adverse events (intraoperatively and during a 6-month follow-up after surgery) and the perioperative cardiorespiratory and inflammatory profile.
Baseline and intraoperative data did not differ between groups. Xenon was non-inferior to sevoflurane, as xenon patients required significantly less noradrenaline intraoperatively to achieve the predefined haemodynamic goals {geometric mean 428 95% confidence interval (CI) 312, 588 vs 1702 1267, 2285 µg, P<0.0001}. No differences were found for safety. Significantly more sevoflurane patients developed postoperative delirium (POD) (hazard ratio 4.2, P=0.044). The average arterial pressure was lower in the sevoflurane group {median75 interquartile range (IQR) 6 vs 72 4 mmHg, P=0.002}. No differences were found for other haemodynamic parameters, the respiratory profile and the perioperative release of inflammatory cytokines, troponin T, serum protein S-100β and erythropoietin.
Compared with sevoflurane, xenon anaesthesia allows a significant reduction in vasopressor administration in OPCAB surgery. Moreover, xenon anaesthesia was associated with a lower risk for POD, a finding that has to be confirmed in larger studies.
ClinicalTrials.gov (NCT01757106) and EudraCT (2012-002316-12).
Postoperative cognitive dysfunction (POCD) is being recognized as a complication contributing to perioperative morbidity and mortality of the elderly. We hypothesized that the use of the ...shorter-acting volatile anaesthetic desflurane would be associated with less incidence of POCD when compared with sevoflurane.
Approved by the local ethical committee, 80 patients (aged 65–75 yr) were enrolled in this randomized, double-blinded study. Patients were allocated to either the desflurane (n=40) or the sevoflurane (n=40) group. The primary outcome was the cognitive Test for Attentional Performance with its subtests Alertness, Divided Attention, Visual Scanning, Working Memory, and Reaction Change. In addition, Paper–Pencil Tests Well-being Test BF-S, Recall of Digit Span (DST), Digit-Symbol-Substitution Test, Trail Making Tests A and B, and Spielberg State-Trait Anxiety Inventory were measured. After baseline assessment 12–24 h before operation, patients were followed up 6–8 and 66–72 h after operation. Among other outcome parameters, emergence times from anaesthesia and modified Aldrete scores were recorded.
There was no difference in the incidence of POCD. However, according to the Paper–Pencil Tests, significant improvements for the desflurane group could be detected (Well-being Test at 6–8 h, DST at 6–8 h, and Trail Making Test at 66–72 h). Emergence was significantly faster in the desflurane group for ‘time to open eyes’ and ‘time to extubation’.
The total incidence of POCD showed no differences between the desflurane and the sevoflurane groups. However, the tests Well-being scale, DST, and Trail Making Test, emergence times, and patients’ satisfaction were in favour of desflurane.
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