Personalized perioperative blood pressure management in patients having major non-cardiac surgery: A bicentric pilot randomized trial.

Study Objective: We hypothesize that personalized perioperative blood pressure management maintaining intraoperative mean arterial pressure (MAP) above the preoperative mean nighttime MAP reduces perfusion-related organ injury compared to maintaining intraoperative MAP above 65 mmHg in patients having major non-cardiac surgery. Before testing this hypothesis in a large-scale trial, we performed this bicentric pilot trial to determine a) if performing preoperative automated nighttime blood pressure monitoring to calculate personalized intraoperative MAP targets is feasible; b) in what proportion of patients the preoperative mean nighttime MAP clinically meaningfully differs from a MAP of 65 mmHg; and c) if maintaining intraoperative MAP above the preoperative mean nighttime MAP is feasible in patients having major non-cardiac surgery.

Design: Bicentric pilot randomized trial.

Coronary Microvascular Dysfunction in Acute Cholestasis-Induced Liver Injury.

Background: Previous studies have shown cardiac abnormalities in acute liver injury, suggesting a potential role in the associated high mortality.

Methods: We designed an experimental study exploring the short-term effects of acute cholestasis-induced liver injury on cardiac function and structure in a rodent bile duct ligation (BDL) model to elucidate the potential interplay. Thirty-seven male rats were subjected to BDL surgery ( = 28) or served as sham-operated ( = 9) controls.

Intrinsic mechanisms of right ventricular autoregulation.

To elucidate the adaptation of the right ventricle to acute and intermittently sustained afterload elevation, targeted preload reductions and afterload increases were implemented in a porcine model involving 12 pigs. Preload reduction was achieved via balloon occlusion of the inferior vena cava before, immediately and 5 min after acute afterload elevation induced by pulmonary artery occlusion or thromboxane A2 analog (U46619) infusion. Ventricular response was monitored by registration of pressure-volume (PV) loops using a conductance catheter.

Evaluation of score parameters for severity assessment of surgery and liver cirrhosis in rats.

Severity assessment in animals is an ongoing field of research. In particular, the question of objectifiable and meaningful parameters of score-sheets, as well as their best combination, arise. This retrospective analysis investigates the suitability of a score-sheet for assessing severity and seeks to optimise it for predicting survival in 89 male Sprague Dawley rats (), during an experiment evaluating the influence of liver cirrhosis by bile duct ligation (BDL) on vascular healing.

[Anesthesia for aortic valve stenosis : Anesthesiological management of patients with aortic valve stenosis during noncardiac surgery].

Aortic valve stenosis is a common condition that requires an anesthesiologist's in-depth knowledge of the pathophysiology, diagnostics and perioperative features of the disease. A newly diagnosed aortic valve stenosis is often initially identified from the anamnesis (dyspnea, syncope, angina pectoris) or a suspicious auscultation finding during the anesthesiologist's preoperative assessment. Interdisciplinary collaboration is essential to ensure the optimal management of these patients in the perioperative setting.

Production of antiviral "OP7 chimera" defective interfering particles free of infectious virus.

Defective interfering particles (DIPs) of influenza A virus (IAV) are suggested for use as broad-spectrum antivirals. We discovered a new type of IAV DIP named "OP7" that carries point mutations in its genome segment (Seg) 7 instead of a deletion as in conventional DIPs (cDIPs). Recently, using genetic engineering tools, we generated "OP7 chimera DIPs" that carry point mutations in Seg 7 plus a deletion in Seg 1.

Generation of "OP7 chimera" defective interfering influenza A particle preparations free of infectious virus that show antiviral efficacy in mice.

Influenza A virus (IAV) defective interfering particles (DIPs) are considered as new promising antiviral agents. Conventional DIPs (cDIPs) contain a deletion in the genome and can only replicate upon co-infection with infectious standard virus (STV), during which they suppress STV replication. We previously discovered a new type of IAV DIP "OP7" that entails genomic point mutations and displays higher antiviral efficacy than cDIPs.

Broad-Spectrum Antiviral Activity of Influenza A Defective Interfering Particles against Respiratory Syncytial, Yellow Fever, and Zika Virus Replication In Vitro.

New broadly acting and readily available antiviral agents are needed to combat existing and emerging viruses. Defective interfering particles (DIPs) of influenza A virus (IAV) are regarded as promising options for the prevention and treatment of IAV infections. Interestingly, IAV DIPs also inhibit unrelated viral infections by stimulating antiviral innate immunity.

Bleeding management: rFVIIIFc in hemophilia A and liver transplantation.

Background: In patients with severe hemophilia A prolonged bleeding may occur even in cases of minor trauma or surgery.

Objective: To investigate the feasibility and efficacy of a recombinant extended half-life (EHL) FVIII concentrate for perioperative bleeding management in a patient with severe hemophilia A undergoing liver transplantation.

Material And Methods: Prior to transplantation FVIII activity and perioperatively required FVIII supply were estimated.

Production of retroviral vectors in continuous high cell density culture.

Retroviral vectors derived from murine leukemia virus (MLV) are used in somatic gene therapy applications e.g. for genetic modification of hematopoietic stem cells.

Experimental Liver Cirrhosis Inhibits Restenosis after Balloon Angioplasty.

The effect of liver cirrhosis on vascular remodeling in vivo remains unknown. Therefore, this study investigates the influence of cholestatic liver cirrhosis on carotid arterial remodeling. A total of 79 male Sprague Dawley rats underwent bile duct ligation (cirrhotic group) or sham surgery (control group) and 28 days later left carotid artery balloon dilatation; 3, 7, 14 and 28 days after balloon dilatation, the rats were euthanized and carotid arteries were harvested.

Cirrhotic Cardiomyopathy Following Bile Duct Ligation in Rats-A Matter of Time?

Cirrhotic patients often suffer from cirrhotic cardiomyopathy (CCM). Previous animal models of CCM were inconsistent concerning the time and mechanism of injury; thus, the temporal dynamics and cardiac vulnerability were studied in more detail. Rats underwent bile duct ligation (BDL) and a second surgery 28 days later.

Novel suspension retroviral packaging cells generated by transposition using transposase encoding mRNA advance vector yields and enable production in bioreactors.

To date, the establishment of high-titer stable viral packaging cells (VPCs) at large scale for gene therapeutic applications is very time- and cost-intensive. Here we report the establishment of three human suspension 293-F-derived ecotropic MLV-based VPCs. The classic stable transfection of an EGFP-expressing transfer vector resulted in a polyclonal VPC pool that facilitated cultivation in shake flasks of 100 mL volumes and yielded high functional titers of more than 1 × 10 transducing units/mL (TU/mL).

Comparative assessment of coronary physiology using transthoracic pulsed-wave Doppler and myocardial contrast echocardiography in rats.

Background: Coronary physiology assessment in rodents by ultrasound is an excellent noninvasive and easy to perform technique, including pulsed-wave Doppler (PWD) and myocardial contrast echocardiography (MCE). Both techniques and the corresponding calculated parameters were investigated in this study at rest as well as their response to pharmacologically induced stress.

Methods: Left ventricular myocardial function was assessed in eight anaesthetised rats using transthoracic echocardiography.

In Vivo Evaluation of a Novel Control Algorithm for Left Ventricular Assist Devices Based Upon Ventricular Stroke Work.

The physical fitness of patients with terminal heart failure and an implanted left ventricular assist device (LVAD) might be improved by load-adaptive control of the LVAD. In this study, three control strategies for LVAD were compared in eight pigs: (1) a constant stroke work (CSW) control strategy that ensures a constant ventricular load using ventricular stroke work as the control variable; (2) a work ratio (WR) controller that maintains a constant ratio of ventricular work to hydraulic pump work; and (3) a controller that maintains the pump pace at a constant speed (CS). Biventricular heart insufficiency was induced by increased isoflurane application, and preload, afterload, and contractility alterations were performed.

Serum from Patients with Severe Alcoholic Liver Cirrhosis Inhibits Proliferation and Migration of Human Coronary Artery Smooth Muscle Cells.

Liver cirrhosis has been associated with an increased risk of coronary artery disease and clinical complications following percutaneous coronary revascularization. The present study is based on the hypothesis that cirrhosis may influence intimal hyperplasia following PCI. Sera from 10 patients with alcoholic liver cirrhosis and 10 age-matched healthy controls were used to stimulate cultured human coronary artery smooth muscle cells (HCASMC) for 48 h.

Effect of Aprotinin on Liver Injury after Transplantation of Extended Criteria Donor Grafts in Humans: A Retrospective Propensity Score Matched Cohort Analysis.

The number of patients awaiting liver transplantation still widely exceeds the number of donated organs available. Patients receiving extended criteria donor (ECD) organs are especially prone to an aggravated ischemia reperfusion syndrome during liver transplantation leading to massive hemodynamic stress and possible impairment in organ function. Previous studies have demonstrated aprotinin to ameliorate reperfusion injury and early graft survival.

Cardiovascular Evaluation of Liver Transplant Patients by Using Coronary Calcium Scoring in ECG-Synchronized Computed Tomographic Scans.

Background: The goal of cardiac evaluation of patients awaiting orthotopic liver transplantation (OLT) is to identify the patients at risk for cardiovascular events (CVEs) in the peri- and postoperative periods by opportunistic evaluation of coronary artery calcium (CAC) in non-gated abdominal computed tomographs (CT).

Methods: We hypothesized that in patients with OLT, a combination of Lee's revised cardiac index (RCRI) and CAC scoring would improve diagnostic accuracy and prognostic impact compared to non-invasive cardiac testing. Therefore, we retrospectively evaluated 169 patients and compared prediction of CVEs by both methods.

Cell culture-based production of defective interfering influenza A virus particles in perfusion mode using an alternating tangential flow filtration system.

Respiratory diseases including influenza A virus (IAV) infections represent a major threat to human health. While the development of a vaccine requires a lot of time, a fast countermeasure could be the use of defective interfering particles (DIPs) for antiviral therapy. IAV DIPs are usually characterized by a large internal deletion in one viral RNA segment.

Multiscale model of defective interfering particle replication for influenza A virus infection in animal cell culture.

Cell culture-derived defective interfering particles (DIPs) are considered for antiviral therapy due to their ability to inhibit influenza A virus (IAV) production. DIPs contain a large internal deletion in one of their eight viral RNAs (vRNAs) rendering them replication-incompetent. However, they can propagate alongside their homologous standard virus (STV) during infection in a competition for cellular and viral resources.

Acute myocardial injury secondary to severe acute liver failure: A retrospective analysis supported by animal data.

To investigate whether acute liver failure (ALF) leads to secondary acute myocardial injury, 100 ALF patients that were retrospectively identified in a single center based on ICD 10 codes and 8 rats from an experimental study that died early after bile duct ligation (BDL) were examined. Creatine kinase (CK), creatine kinase-MB isoenzyme (CKMB) and cardiac troponin-I (cTnI) were analyzed as markers of myocardial injury. For histological analysis, hematoxylin-eosin (HE), elastic Van Gieson (EVG), CD41 and myeloperoxidase were used to stain rat hearts.

Antiviral Activity of Influenza A Virus Defective Interfering Particles against SARS-CoV-2 Replication In Vitro through Stimulation of Innate Immunity.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing coronavirus disease 2019 (COVID-19) emerged in late 2019 and resulted in a devastating pandemic. Although the first approved vaccines were already administered by the end of 2020, worldwide vaccine availability is still limited. Moreover, immune escape variants of the virus are emerging against which the current vaccines may confer only limited protection.

evaluation of two adaptive Starling-like control algorithms for left ventricular assist devices.

The implantation of a left ventricular assist device (LVAD) is often the only therapy in terminal heart failure (HF). However, despite technical advancements, the physical fitness of the patients is still limited. One strategy to improve the benefits of ventricular assist device therapy might be the implementation of load adaptive control strategies.

Cell culture-based production and in vivo characterization of purely clonal defective interfering influenza virus particles.

Background: Infections with influenza A virus (IAV) cause high morbidity and mortality in humans. Additional to vaccination, antiviral drugs are a treatment option. Besides FDA-approved drugs such as oseltamivir or zanamivir, virus-derived defective interfering (DI) particles (DIPs) are considered promising new agents.