Matrix Metalloproteinasen und deren Inhibitoren im Verlauf der experimentellen chronischen Pankreatitis

Ziel der vorliegenden Arbeit waren Untersuchungen zur Expression von Matrix Metalloproteinasen (MMPs) und deren Inhibitoren, den Tissue Inhibitors of Matrix Metalloproteinases (TIMPs), im Verlauf einer tierexperimentellen chronischen Pankreatitis sowie in kultivierten pankreatische Stellatezellen. Ein Anstieg der Expression von TIMPs und MMPs während der experimentellen Pankreatitis weist auf einen Zusammenhang zwischen den Proteinasen und ihren Inhibitoren hin. Dieser begünstigt möglicherweise die Infiltration immunokompetenter Zellen, welche zu einer Verstärkung und zur Chronifizierung der Pankreatitis beiträgt.In order to investigate the matrix turnover during the course of the experimental pancreatitis, we studied the expression of the extracellular matrix (ECM) degrading enzymes, the matrix metalloproteinases (MMP) and their inhibitors, the tissue inhibitors of metalloproteinases (TIMP), in the pancreas, as well as the MMP activity in Stellate cells culture. Increased expressions of TIMPs during the experimental pancreatitis accompanied by differences in MMP-RNA levels and elevated MMP activity in activated stellate cells indicate an important role for the relation between proteinases and their inhibitors

The incidence of postoperative vasopressor usage: protocol for a prospective international observational cohort study (SQUEEZE)

Background: Postoperative hypotension is common after major non-cardiac surgery, due predominantly to vasodilation. Administration of infused vasopressors postoperatively may often be considered a surrogate indicator of vasodilation. The incidence of postoperative vasopressors has never been described for non-cardiac surgery, nor have outcomes associated with their use. This paper presents a protocol for a prospective international cohort study to address these gaps in knowledge. The primary objectives are to estimate the proportion of patients who receive postoperative vasopressor infusions (PVI) and to document the variation in this proportion between hospitals and internationally. Furthermore, we will identify factors in variation of care (patient, condition, surgery, and intraoperative management) associated with receipt of PVI and investigate how PVI use is associated with patient outcomes, including organ dysfunction, length of hospital stay, and 30-day in-hospital mortality. Method: This will be a prospective, international, multicentre cohort study that includes all adult (≥ 18 years) non-cardiac surgical patients in participating centres. Patients undergoing cardiac, obstetric, or day-case surgery will be excluded. We will recruit two cohorts of patients: cohort A will include all eligible patients admitted to participating hospitals for seven consecutive days. Cohort B will include 30 sequential patients per hospital, with the single additional inclusion criterion of postoperative vasopressor usage. We expect to collect data on approximately 40,000 patients for cohort A and 12,800 patients for cohort B. Discussion: While in cardiac surgery, clinical trials have informed the choice of vasopressors used to treat postoperative vasoplegia; there remains equipoise over the best approach in non-cardiac surgery. Our study will represent the first large-scale assessment of the use of vasopressors after non-cardiac surgery. These data will inform future studies, including trials of different vasopressors and potential management options to improve outcomes and reduce resource use after surgery. Trial registration: ClinicalTrials.gov Identifier: NCT03805230, 15 January 2019

What are the optimum components in a care bundle aimed at reducing post-operative pulmonary complications in high-risk patients?

BACKGROUND: Post-operative pulmonary complications (POPC) are common, predictable and associated with increased morbidity and mortality, independent of pre-operative risk. Interventions to reduce the incidence of POPC have been studied individually, but the use of a care bundle has not been widely investigated. The purpose of our work was to use Delphi consensus methodology and an independently chosen expert panel to formulate a care bundle for patients identified as being at high of POPC, as preparation towards an evaluation of its effectiveness at reducing POPC. METHODS: We performed a survey of members of the ESICM POIC section to inform a Delphi consensus and to share their opinions on a care bundle to reduce POPC, the POPC-CB. We formed a team of 36 experts to participate in and complete an email-based Delphi consensus over three rounds, leading to the formulation of the POPC-CB. RESULTS: The survey had 362 respondents and informed the design of the Delphi consensus. The Delphi consensus resulted in a proposed POPC-CB that incorporates components before surgery-supervised exercise programmes and inspiratory muscle training, during surgery, low tidal volume ventilation with individualised PEEP (positive end-expiratory pressure), use of routine monitoring to avoid hyperoxia and efforts made to limit neuromuscular blockade, and post-operatively, deep breathing exercises and elevation of the head of the bed. CONCLUSION: A care bundle has been suggested for evaluation in surgical patients at high risk of POPC. Evaluation of feasibility of both implementation and effectiveness is now indicated

Implementing screening for myocardial injury in non-cardiac surgery: perspectives of an ad-hoc interdisciplinary expert group

Objectives. Perioperative myocardial injury (PMI) is increasingly recognised as an important complication of non-cardiac surgery, with often clinically silent presentation, but detrimental prognosis. Active screening for PMI, involving the detection of dynamic and elevated levels of cardiac troponin, has recently been advocated by an increasing number of guidelines; however, active PMI screening has not been reflected in clinical practice. Design. As consensus on a common screening and management pathway is lacking, we synthesise the current evidence to provide suggestions on the selection of patients for screening, organisation of a screening program, and a potential management pathway, building upon a recently published perioperative screening algorithm. Results. Screening should be performed using high-sensitivity assays both preoperatively and postoperatively (postoperative Days 1 and 2) in patients at high-risk of experiencing perioperative complications. Conclusion. This expert opinion piece by an interdisciplinary group of predominantly Norwegian clinicians aims to assist healthcare professionals planning to implement guideline-recommended PMI screening at a local level in order to improve patient outcomes following non-cardiac surgery.publishedVersio

On Component Forces in Physics: A Pragmatic View

Do component forces exist? I argue that the answer lies in the affirmative, on historical and operational grounds

Sex difference and intra-operative tidal volume: Insights from the LAS VEGAS study

BACKGROUND: One key element of lung-protective ventilation is the use of a low tidal volume (VT). A sex difference in use of low tidal volume ventilation (LTVV) has been described in critically ill ICU patients.OBJECTIVES: The aim of this study was to determine whether a sex difference in use of LTVV also exists in operating room patients, and if present what factors drive this difference.DESIGN, PATIENTS AND SETTING: This is a posthoc analysis of LAS VEGAS, a 1-week worldwide observational study in adults requiring intra-operative ventilation during general anaesthesia for surgery in 146 hospitals in 29 countries.MAIN OUTCOME MEASURES: Women and men were compared with respect to use of LTVV, defined as VT of 8 ml kg-1 or less predicted bodyweight (PBW). A VT was deemed 'default' if the set VT was a round number. A mediation analysis assessed which factors may explain the sex difference in use of LTVV during intra-operative ventilation.RESULTS: This analysis includes 9864 patients, of whom 5425 (55%) were women. A default VT was often set, both in women and men; mode VT was 500 ml. Median [IQR] VT was higher in women than in men (8.6 [7.7 to 9.6] vs. 7.6 [6.8 to 8.4] ml kg-1 PBW, P < 0.001). Compared with men, women were twice as likely not to receive LTVV [68.8 vs. 36.0%; relative risk ratio 2.1 (95% CI 1.9 to 2.1), P < 0.001]. In the mediation analysis, patients' height and actual body weight (ABW) explained 81 and 18% of the sex difference in use of LTVV, respectively; it was not explained by the use of a default VT.CONCLUSION: In this worldwide cohort of patients receiving intra-operative ventilation during general anaesthesia for surgery, women received a higher VT than men during intra-operative ventilation. The risk for a female not to receive LTVV during surgery was double that of males. Height and ABW were the two mediators of the sex difference in use of LTVV.TRIAL REGISTRATION: The study was registered at Clinicaltrials.gov, NCT01601223

Ten golden rules for optimal antibiotic use in hospital settings: the WARNING call to action

Antibiotics are recognized widely for their benefits when used appropriately. However, they are often used inappropriately despite the importance of responsible use within good clinical practice. Effective antibiotic treatment is an essential component of universal healthcare, and it is a global responsibility to ensure appropriate use. Currently, pharmaceutical companies have little incentive to develop new antibiotics due to scientific, regulatory, and financial barriers, further emphasizing the importance of appropriate antibiotic use. To address this issue, the Global Alliance for Infections in Surgery established an international multidisciplinary task force of 295 experts from 115 countries with different backgrounds. The task force developed a position statement called WARNING (Worldwide Antimicrobial Resistance National/International Network Group) aimed at raising awareness of antimicrobial resistance and improving antibiotic prescribing practices worldwide. The statement outlined is 10 axioms, or “golden rules,” for the appropriate use of antibiotics that all healthcare workers should consistently adhere in clinical practice