Showing papers by "Gernot Marx published in 2014"

Translation control of TAK1 mRNA by hnRNP K modulates LPS-induced macrophage activation.

Abstract: Macrophage activation by bacterial lipopolysaccharides (LPS) is induced through Toll-like receptor 4 (TLR4). The synthesis and activity of TLR4 downstream signaling molecules modulates the expression of pro- and anti-inflammatory cytokines. To address the impact of post-transcriptional regulation on that process, we performed RIP-Chip analysis. Differential association of mRNAs with heterogeneous nuclear ribonucleoprotein K (hnRNP K), an mRNA-specific translational regulator in differentiating hematopoietic cells, was studied in noninduced and LPS-activated macrophages. Analysis of interactions affected by LPS revealed several mRNAs encoding TLR4 downstream kinases and their modulators. We focused on transforming growth factor-β-activated kinase 1 (TAK1) a central player in TLR4 signaling. HnRNP K interacts specifically with a sequence in the TAK1 mRNA 3′ UTR in vitro. Silencing of hnRNP K does not affect TAK1 mRNA synthesis or stability but enhances TAK1 mRNA translation, resulting in elevated TNF-α, IL-1β, and IL-10 mRNA expression. Our data suggest that the hnRNP K-3′ UTR complex inhibits TAK1 mRNA translation in noninduced macrophages. LPS-dependent TLR4 activation abrogates translational repression and newly synthesized TAK1 boosts macrophage inflammatory response.

Voluntary peer review as innovative tool for quality improvement in the intensive care unit--a retrospective descriptive cohort study in German intensive care units.

Abstract: Introduction: Quality improvement and safety in intensive care are rapidly evolving topics. However, there is no gold standard for assessing quality improvement in intensive care medicine yet. In 2007 a pilot project in German intensive care units (ICUs) started using voluntary peer reviews as an innovative tool for quality assessment and improvement. We describe the method of voluntary peer review and assessed its feasibility by evaluating anonymized peer review reports and analysed the thematic clusters highlighted in these reports. Methods: Retrospective data analysis from 22 anonymous reports of peer reviews. All ICUs – representing over 300 patient beds – had undergone voluntary peer review. Data were retrieved from reports of peers of the review teams and representatives of visited ICUs. Data were analysed with regard to number of topics addressed and results of assessment questionnaires. Reports of strengths, weaknesses, opportunities and threats (SWOT reports) of these ICUs are presented. Results: External assessment of structure, process and outcome indicators revealed high percentages of adherence to predefined quality goals. In the SWOT reports 11 main thematic clusters were identified representative for common ICUs. 58.1% of mentioned topics covered personnel issues, team and communication issues as well as organisation and treatment standards. The most mentioned weaknesses were observed in the issues documentation/reporting, hygiene and ethics. We identified several unique patterns regarding quality in the ICU of which long-term personnel problems und lack of good reporting methods were most interesting Conclusion: Voluntary peer review could be established as a feasible and valuable tool for quality improvement. Peer reports addressed common areas of interest in intensive care medicine in more detail compared to other methods like measurement of quality indicators.

A novel application for assessing diaphragmatic function by ultrasonic deformation analysis in noninvasively ventilated healthy young adults.

Abstract: Purpose: Noninvasive pressure support ventilation is intended to relieve the load on respiratory muscles and to prevent exhaustion. This includes continuous positive airway pressure (CPAP) as well as pressure support ventilation (PSV). Speckle tracking echocardiography (STE) allows quantification of tissue deformation by tracing characteristic grayscale patterns, independent of the acquisition angle. The aim of the present study was to assess the applicability of using STE as a way to investigate diaphragm movement using deformation analysis as a parameter for respiratory workload. Materials and Methods: Healthy male subjects (n = 13, 27 ± 7 years) were treated while in a seated supine position with the following respirator settings: regular breathing, 5 mbar CPAP, CPAP + 5 / + 10 / + 15 mbar PSV. A 2 – 4 MhZ M5S phased array sector transducer was used on a Vivid E 9 (GE, Horton, Norway) to visualize the diaphragm. The inspiratory peak transverse strain was measured as a parameter of maximal inspiratory muscle workload and compared to the M-mode-based fractional thickening (FT). Results: Both the FT and the transverse strain increased significantly under CPAP and PSV. The transverse strain correlated well with the FT (r = 0.753; p Conclusion: The results measured by STE were comparable to the M-mode-based measurements. The capturing of a larger diaphragmatic sample area and movement tracking possibly lead to higher precision compared to one-dimensional M-mode. The use of STE in patients might provide a reproducible, bedside method to analyze the respiratory workload. Due to the larger sampling area, it might prove superior to mere M-mode acquisition.

Accuracy and precision of calibrated arterial pulse contour analysis in patients with subarachnoid hemorrhage requiring high-dose vasopressor therapy: a prospective observational clinical trial

Abstract: Calibrated arterial pulse contour analysis has become an established method for the continuous monitoring of cardiac output (PCCO). However, data on its validity in hemodynamically instable patients beyond the setting of cardiac surgery are scarce. We performed the present study to assess the validity and precision of PCCO-measurements using the PiCCO™-device compared to transpulmonary thermodilution derived cardiac output (TPCO) as the reference technique in neurosurgical patients requiring high-dose vasopressor-therapy. A total of 20 patients (16 females and 4 males) were included in this prospective observational clinical trial. All of them suffered from subarachnoid hemorrhage (Hunt&Hess grade I-V) due to rupture of a cerebral arterial aneurysm and underwent high-dose vasopressor therapy for the prevention/treatment of delayed cerebral ischemia (DCI). Simultaneous CO measurements by bolus TPCO and PCCO were obtained at baseline as well as 2 h, 6 h, 12 h, 24 h, 48 h and 72 h after inclusion. PCCO- and TPCO-measurements were obtained at baseline as well as 2 h, 6 h, 12 h, 24 h, 48 h and 72 h after inclusion. Patients received vasoactive support with (mean ± standard deviation, SD) 0.57 ± 0.49 μg · kg-1 · min-1 norepinephrine resulting in a mean arterial pressure of 103 ± 13 mmHg and a systemic vascular resistance of 943 ± 248 dyn · s · cm-5. 136 CO-data pairs were analyzed. TPCO ranged from 5.2 to 14.3 l · min-1 (mean ± SD 8.5 ± 2.0 l · min-1) and PCCO ranged from 5.0 to 14.4 l · min-1 (mean ± SD 8.6 ± 2.0 l · min-1). Bias and limits of agreement (1.96 SD of the bias) were −0.03 ± 0.82 l · min-1 and 1.62 l · min-1, resulting in an overall percentage error of 18.8%. The precision of PCCO-measurements was 17.8%. Insufficient trending ability was indicated by concordance rates of 74% (exclusion zone of 15% (1.29 l · min-1)) and 67% (without exclusion zone), as well as by polar plot analysis. In neurosurgical patients requiring extensive vasoactive support, CO values obtained by calibrated PCCO showed clinically and statistically acceptable agreement with TPCO-measurements, but the results from concordance and polar plot analysis indicate an unreliable trending ability.

Optimizing the pharmacotherapy of vascular surgery patients by medication reconciliation

Abstract: Aim Medication errors may occur at any stage during the medication process and can lead to preventable adverse drug events and patients' harm. Pharmacists' support for reconcilable medication has been shown to be effective, rectifying errors and inaccuracies of the drug treatment and in the increase of medication safety. However, none of the previous studies focused on vascular patients. We investigated the nature and frequency of drug-related problems (DRPs) including the amount of potentially inappropriate medication (PIM) prescribed for elderly patients suffering from vascular diseases and the influence of pharmacists in the improvement of cardiovascular medication. Methods After the patients' routine admission process, medication reconciliation was performed. Therefore, a pharmacist obtained an accurate medication use history. The patients' drug therapy was critically screened for DRPs and referring to this, intervention was made by the pharmacist and communicated to the physician if necessary. Potentially inappropriate medication in the elderly was reviewed through a retrospective analysis using the Priscus-List. DRPs were documented anonymously and classified. Results We identified 138 DRPs among 105 patients. Sixty-five patients experienced at least 1 DRP, accordingly 1.3 DRPs per patient. In total, 43 unintended discrepancies between current medication and admission medication were detected with an overall rate of 0.41 per patient; 100 interventions were made of which 56 resulted in explicit recommendations for prescription changes. Drug classes frequently affected by DRPs were antihypertensive in 23.9%, antithrombotic agents in 19.3% and lipid lowering agents in 12.1%. In a retrospective analysis of the home medication, 12 definite PIM were identified in 49 elderly patients. Conclusion DRPs are common in the medication of vascular surgery patients and may be improved by pharmacists.

Are chlorhexidine-containing dressings safe for use with ventricular drainages?

Abstract: The purpose of this report was to assess the safety and application of chlorhexidine (CHG)-containing dressings—shown to reduce central line infection rates markedly—for external ventricular drainages (EVDs) and lumbar drainages (LDs). Cerebrospinal fluid samples of patients receiving standard dressings and CHG-containing dressing (ten each) were analyzed by high-performance liquid chromatography for the presence of CHG. The application was evaluated. CHG was not detectable in all samples. The dressings’ application for EVDs and LDs worked without problems. Thus, the use of CHG-containing dressings for EVDs and LDs seems to be safe. Further studies addressing their infection reduction potential are warranted.

Ventilatorinduzierte diaphragmale Dysfunktion

Abstract: Die mechanische Beatmung ist fur Patienten mit respiratorischem Versagen oder im Rahmen der tiefen Sedierung lebensrettend. Wahrend kontinuierlicher mandatorischer Beatmung ist das Diaphragma inaktiviert und unterliegt einer pathophysiologischen Kaskade, die zum Kraftverlust und zur Verringerung der Muskelfasermasse fuhrt. Diese Prozesse sind im Gegensatz zur peripheren Skelettmuskulatur bereits nach 12 h nachweisbar und haben Einfluss auf die Beatmungsentwohnung von Intensivpatienten – und damit auf Letalitat sowie Morbiditat. Studien der letzten Jahre haben tierexperimentell die pathophysiologischen Zusammenhange untersucht und sind durch klinische Untersuchungen bestatigt worden. Diese Ubersicht beschreibt die biochemischen Zusammenhange, Einflusse von Pharmaka und Interventionen zur Prophylaxe.

Neue Weiterbildung Intensivmedizin: Bewährtes Konzept mit neuen kompetenzbasierten Inhalten

Abstract: Bereich in der modernen Medizin, welcher ohne jeden Zweifel eine spezielle Weiterbildung auf der Basis der verschiedenen Facharztqualifikationen erfordert. Kritisch kranke Patienten benötigen nicht nur eine kontinuierliche 24-stündige Betreuung durch einen Arzt, sondern durch einen Arzt, der den besonderen Herausforderungen gewachsen ist. Deswegen wurde in den 2013 publizierten überarbeiteten Qualitätsindikatoren Intensivmedizin aufgenommen, dass zumindest in der Kernarbeitszeit ein Facharzt mit Zusatzqualifikation Intensivmedizin auf der Intensivstation präsent sein muss [1]. Die Grundlagen der ärztlichen Weiterbildung werden auf europäischer Ebene in der UEMS (Union Européenne des Médicins Spécialistes – Vereinigung der Europäischen Medizinischen Fachgesellschaften) geregelt, in der alle medizinischen Fachdisziplinen repräsentiert sind. Für die Intensivmedizin als interdisziplinäres Fachgebiet wurde 1999 im Rahmen der UEMS ein interdisziplinäres Komitee gegründet, das „Multidisciplinary Joint Committee of Intensive Care Medicine (MJCICM)“, welches sich seitdem mit den speziellen Anforderungen in dem komplexen Bereich beschäftigt [2,3].

The Importance of Weaning for Successful Treatment of Respiratory Failure

Abstract: Identification of acute respiratory failure and treatment of the underlying cause(s) are crucial but also difficult challenges in ICU management. Weaning from mechanical ventilation must be conducted in a timely manner because invasive, prolonged mechanical ventilation can be a significant hazard with a negative influence on the weaning process. Interestingly, the process of weaning from mechanical ventilation represents approximately 40–50 % of the duration of mechanical ventilation [1–3] and is directly associated with patient prognosis [4].