Acute cholecystitis – early laparoskopic surgery versus antibiotic therapy and delayed elective cholecystectomy: ACDC-study

<p>Abstract</p> <p>Background</p> <p>Acute cholecystitis occurs frequently in the elderly and in patients with gall stones. Most cases of severe or recurrent cholecystitis eventually require surgery, usually laparoscopic cholecystectomy in the Western World. It is unclear whether an initial, conservative approach with antibiotic and symptomatic therapy followed by delayed elective surgery would result in better morbidity and outcome than immediate surgery. At present, treatment is generally determined by whether the patient first sees a surgeon or a gastroenterologist. We wish to investigate whether both approaches are equivalent. The primary endpoint is the morbidity until day 75 after inclusion into the study.</p> <p>Design</p> <p>A multicenter, prospective, randomized non-blinded study to compare treatment outcome, complications and 75-day morbidity in patients with acute cholecystitis randomized to laparoscopic cholecystectomy within 24 hours of symptom onset or antibiotic treatment with moxifloxacin and subsequent elective cholecystectomy. For consistency in both arms moxifloxacin, a fluorquinolone with broad spectrum of activity and high bile concentration is used as antibiotic. Duration: October 2006 – November 2008</p> <p>Organisation/Responsibility</p> <p>The trial was planned and is being conducted and analysed by the Departments of Gastroenterology and General Surgery at the University Hospital of Heidelberg according to the ethical, regulatory and scientific principles governing clinical research as set out in the Declaration of Helsinki (1989) and the Good Clinical Practice guideline (GCP).</p> <p>Trial Registration</p> <p>ClinicalTrials.gov NCT00447304</p

QT dispersion in patients with systemic lupus erythematosus: the impact of disease activity

<p>Abstract</p> <p>Background</p> <p>Patients with systemic lupus erythematosus (SLE) have increased cardiovascular morbidity and mortality. Although autopsy studies have documented that the heart is affected in most SLE patients, clinical manifestations occur in less than 10%. QT dispersion is a new parameter that can be used to assess homogeneity of cardiac repolarization and autonomic function. We compared the increase in QT dispersion in SLE patients with high disease activity and mild or moderate disease activity.</p> <p>Methods and Results</p> <p>One hundred twenty-four patients with SLE were enrolled in the study. Complete history and physical exam, ECG, echocardiography, exercise test and SLE disease activity index (SLEDAI) were recorded. Twenty patients were excluded on the basis of our exclusion criteria. The patients were divided to two groups based on SLEDAI: 54 in the high-score group (SLEDAI > 10) and 50 in the low-score group (SLEDAI < 10).</p> <p>QT dispersion was significantly higher in high-score group (58.31 ± 18.66 vs. 47.90 ± 17.41 respectively; <it>P </it>< 0.004). QT dispersion was not significantly higher in patients who had received hydroxychloroquine (54.17 ± 19.36 vs. 50.82 ± 15.96, <it>P </it>= 0.45) or corticosteroids (53.58 ± 19.16 vs. 50.40 + 11.59, <it>P </it>= 0.47). There was a statistically significant correlation between abnormal echocardiographic findings (abnormalities of pericardial effusion, pericarditis, pulmonary hypertension and Libman-Sacks endocarditis) and SLEADI (<it>P </it>< 0.004).</p> <p>Conclusions</p> <p>QT dispersion can be a useful, simple noninvasive method for the early detection of cardiac involvement in SLE patients with active disease. Concerning high chance of cardiac involvement, cardiovascular evaluation for every SLE patient with a SLEDAI higher than 10 may be recommended.</p> <p>Trial registration</p> <p>Clinicaltrial.gov registration <a href="http://www.clinicaltrials.gov/ct2/show/NCT01031797">NCT01031797</a></p

Enhancement of CURB65 score with proadrenomedullin (CURB65-A) for outcome prediction in lower respiratory tract infections: Derivation of a clinical algorithm

Proadrenomedullin (ProADM) confers additional prognostic information to established clinical risk scores in lower respiratory tract infections (LRTI). We aimed to derive a practical algorithm combining the CURB65 score with ProADM-levels in patients with community-acquired pneumonia (CAP) and non-CAP-LRTI

Utilizing the Luminex Magnetic Bead-Based Suspension Array for Rapid Multiplexed Phosphoprotein Quantification.

The study of protein phosphorylation is critical for the advancement of our understanding of cellular responses to external and internal stimuli. Phosphorylation, the addition of phosphate groups, most often occurs on serine, threonine, or tyrosine residues due to the action of protein kinases. This structural change causes the protein to become activated (or deactivated) and enables it in turn to initiate the phosphorylation of other proteins in a cascade, eventually causing cell-wide changes such as apoptosis, cell differentiation, and growth (among others). Cellular phosphoprotein pathway dysregulation by mutation or chromosomal instability can often give the cell a selective advantage and lead to cancer. Obviously the understanding of these systems is of huge importance to the field of oncology.This chapter aims to provide a "how to" manual for one such technology, the 96-well plate-based xMAP® platform from Luminex. The system utilizes antibody-bound free-floating magnetic spheres which can easily be removed from suspension via magnetization. There are 100 unique bead sets (moving up to 500 bead sets for the most recent system) identified by the ratio of two dyes coating the microsphere. Each bead set is conjugated to a specific antibody which allows targeted protein extraction from low-concentration lysate solution. Biotinylated secondary antibodies/streptavidin-R-phycoerythrin (SAPE) complexes provide the quantification mechanism for the phosphoprotein of interest

Lung epithelium as a sentinel and effector system in pneumonia – molecular mechanisms of pathogen recognition and signal transduction

Pneumonia, a common disease caused by a great diversity of infectious agents is responsible for enormous morbidity and mortality worldwide. The bronchial and lung epithelium comprises a large surface between host and environment and is attacked as a primary target during lung infection. Besides acting as a mechanical barrier, recent evidence suggests that the lung epithelium functions as an important sentinel system against pathogens. Equipped with transmembranous and cytosolic pathogen-sensing pattern recognition receptors the epithelium detects invading pathogens. A complex signalling results in epithelial cell activation, which essentially participates in initiation and orchestration of the subsequent innate and adaptive immune response. In this review we summarize recent progress in research focussing on molecular mechanisms of pathogen detection, host cell signal transduction, and subsequent activation of lung epithelial cells by pathogens and their virulence factors and point to open questions. The analysis of lung epithelial function in the host response in pneumonia may pave the way to the development of innovative highly needed therapeutics in pneumonia in addition to antibiotics