Frank Stueber

Technical Approach Determines Inflammatory Response after Surgical and Transcatheter Aortic Valve Replacement

Objective To investigate the periprocedural inflammatory response in patients with isolated aortic valve stenosis undergoing surgical aortic valve replacement (SAVR) or transcatheter aortic valve implantation (TAVI) with different technical approaches. Material and Methods Patients were prospectively allocated to one of the following treatments: SAVR using conventional extracorporeal circulation (CECC, n = 47) or minimized extracorporeal circulation (MECC, n = 15), or TAVI using either transapical (TA, n = 15) or transfemoral (TF, n = 24) access. Exclusion criteria included infection, pre-procedural immunosuppressive or antibiotic drug therapy and emergency indications. We investigated interleukin (IL)-6, IL-8, IL-10, human leukocyte antigen (HLA-DR), white blood cell count, high-sensitivity C-reactive protein (hs-CRP) and soluble L-selectin (sCD62L) levels before the procedure and at 4, 24, and 48 h after aortic valve replacement. Data are presented for group interaction (p-values for inter-group comparison) as determined by the Greenhouse-Geisser correction. Results SAVR on CECC was associated with the highest levels of IL-8 and hs-CRP (p<0.017, and 0.007, respectively). SAVR on MECC showed the highest descent in levels of HLA-DR and sCD62L (both p<0.001) in the perioperative period. TA-TAVI showed increased intraprocedural concentration and the highest peak of IL-6 (p = 0.017). Significantly smaller changes in the inflammatory markers were observed in TF-TAVI. Conclusion Surgical and interventional approaches to aortic valve replacement result in inflammatory modulation which differs according to the invasiveness of the procedure. As expected, extracorporeal circulation is associated with the most marked pro-inflammatory activation, whereas TF-TAVI emerges as the approach with the most attenuated inflammatory response. Factors such as the pre-treatment patient condition and the extent of myocardial injury also significantly affect inflammatory biomarker patterns. Accordingly, TA-TAVI is to be classified not as an interventional but a true surgical procedure, with inflammatory biomarker profiles comparable to those found after SAVR. Our study could not establish an obvious link between the extent of the periprocedural inflammatory response and clinical outcome parameters.

A dexamethasone-regulated gene signature is prognostic for poor survival in glioblastoma patients

Background: Dexamethasone is reported to induce both tumor-suppressive and tumor-promoting effects. The purpose of this study was to identify the genomic impact of dexamethasone in glioblastoma stem cell (GSC) lines and its prognostic value; furthermore, to identify drugs that can counter these side effects of dexamethasone exposure. Methods: We utilized 3 independent GSC lines with tumorigenic potential for this study. Whole-genome expression profiling and pathway analyses were done with dexamethasone-exposed and control cells. GSCs were also co-exposed to dexamethasone and temozolomide. Risk scores were calculated for most affected genes, and their associations with survival in The Cancer Genome Atlas and Repository of Molecular Brain Neoplasia Data databases. In silico Connectivity Map analysis identified camptothecin as antagonist to dexamethasone-induced negative effects. Results: Pathway analyses predicted an activation of dexamethasone network (z-score: 2.908). Top activated canonical pathways included “role of breast cancer 1 in DNA damage response” (P=1.07E–04). GSCs were protected against temozolomide-induced apoptosis when coincubated with dexamethasone. Altered cellular functions included cell movement, cell survival, and apoptosis with z-scores of 2.815, 5.137, and –3.122, respectively. CCAAT/enhancer binding protein beta (CEBPB) was activated in a dose dependent manner specifically in slow-dividing “stem-like” cells. CEBPB was activated in dexamethasone-treated orthotopic tumors. Patients with high risk scores had significantly shorter survival. Camptothecin was validated as potential partial neutralizer of dexamethasone-induced oncogenic effects. Conclusions: Dexamethasone exposure induces a genetic program and CEBPB expression in GSCs that adversely affects key cellular functions and response to therapeutics. High risk scores associated with these genes have negative prognostic value in patients. Our findings further suggest camptothecin as a potential neutralizer of adverse dexamethasone-mediated effects.

Discrepancies Between Planned and Actual Operating Room Turnaround Times at a Large Rural Hospital in Germany

Objectives While several factors have been shown to influence operating room (OR) turnaround times, few comparisons of planned and actual OR turnaround times have been performed. This study aimed to compare planned and actual OR turnaround times at a large rural hospital in Northern Germany. Methods This retrospective study examined the OR turnaround data of 875 elective surgery cases scheduled at the Marienhospital, Vechta, Germany, between July and October 2014. The frequency distributions of planned and actual OR turnaround times were compared and correlations between turnaround times and various factors were established, including the time of day of the procedure, patient age and the planned duration of the surgery. Results There was a significant difference between mean planned and actual OR turnaround times (0.32 versus 0.64 hours; P <0.001). In addition, significant correlations were noted between actual OR turnaround times and the time of day of the surgery, patient age, actual duration of the procedure and staffing changes affecting the surgeon or the medical specialty of the surgery (P <0.001 each). The quotient of actual/planned OR turnaround times ranged from 1.733-3.000. Conclusion Significant discrepancies between planned and actual OR turnaround times were noted during the study period. Such findings may be potentially used in future studies to establish a tool to improve OR planning, measure OR management performance and enable benchmarking.

Cerebral microembolism in the critically ill with acute kidney injury (COMET-AKI trial): study protocol for a randomized controlled clinical trial.

BackgroundMicroembolism is a frequent pathological event during extracorporeal renal replacement therapy (RRT). Some previous data indicate that microemboli are generated in patients who are undergoing RRT and that these may contribute to increased cerebrovascular and neurocognitive morbidity in patients with end-stage renal disease. The current trial aims to quantify the microembolic load and respective qualitative composition that effectively reaches the intracerebral circulation in critically ill patients treated with different RRT modalities for acute kidney injury (AKI).Methods/designThe COMET-AKI trial is a prospective, randomized controlled clinical trial with a 2-day clinical assessment period and follow-up visits at 6 and 12 months. Consecutive critically ill patients with AKI on continuous renal replacement therapy (CRRT) scheduled for a switch to intermittent renal replacement therapy (IRRT) will be randomized to either switch to IRRT within the next 24 h or continued CRRT for an additional 24 h. Cerebral microembolic load will be determined at baseline, i.e., before switch (on CRRT for both groups) and on IRRT versus CRRT, whichever group they were randomized to. The primary endpoint is defined as the difference in mean total cerebral microemboli count during the measurement period on CRRT versus IRRT following randomization. Microemboli will be assessed within the RRT circuit by a 1.5-MHz ultrasound detector attached to the venous RRT tubing and cerebral microemboli will be measured in the middle cerebral artery using a 1.6-MHz robotic transcranial Doppler system with automatic classification of Doppler signals as solid or gaseous. In addition to Doppler measurements, patients will be examined by magnetic resonance imaging and neurocognitive tests to gain better understanding into the potential morphological and clinical consequences of embolization.DiscussionThe results of COMET-AKI may help to gain a better insight into RRT modality-associated differences regarding microbubble generation and the cerebral microembolic burden endured by RRT recipients. Furthermore, identification of covariates of microbubble formation and distribution may help to encourage the evolution of next-generation RRT circuits including machinery and/or filters.Trial registrationClinicalTrials.gov, ID: NCT02621749. Registered on 3 December 2015.

Anaesthesia and Rare Metabolic Disorders

Metabolic disorders occur due to abnormal metabolic processes caused by an acquired failure of a metabolic organ or an inherited abnormality of enzymes [1]. The US National Institutes of Health (NIH) Genetic and Rare Diseases Information Center (GARD) currently lists 515 entities as metabolic disorders grouped into 18 subclasses (Table 13.1). Here, we discuss current approaches to evidence-based perioperative management of patients with rare metabolic disorders, i.e. those metabolic diseases with a prevalence/incidence as little as 1:200,000 or fewer [2]. Very rare diseases, or diseases for which prevalence/incidence is unknown, or which are only known to occur in members of a particular family, are regarded as very rare and are not covered. As well, we do not discuss diseases that have not been reported in the English language literature. Our goal is not to be comprehensive, but, rather, to provide a general overview of anaesthesia and rare metabolic disorders.

Differentiation between Staphylococcus aureus and coagulase-negative Staphylococcus species by real-time PCR including detection of methicillin resistants in comparison to conventional microbiology testing.

Staphylococcus aureus has long been recognized as a major pathogen. Methicillin‐resistant strains of S. aureus (MRSA) and methicillin‐resistant strains of S. epidermidis (MRSE) are among the most prevalent multiresistant pathogens worldwide, frequently causing nosocomial and community‐acquired infections.