Inflammatory cytokines and biofilm production sustain Staphylococcus aureus outgrowth and persistence: A pivotal interplay in the pathogenesis of Atopic Dermatitis

Individuals with Atopic dermatitis (AD) are highly susceptible to Staphylococcus aureus colonization. However, the mechanisms driving this process as well as the impact of S. aureus in AD pathogenesis are still incompletely understood. In this study, we analysed the role of biofilm in sustaining S. aureus chronic persistence and its impact on AD severity. Further we explored whether key inflammatory cytokines overexpressed in AD might provide a selective advantage to S. aureus. Results show that the strength of biofilm production by S. aureus correlated with the severity of the skin lesion, being significantly higher (P < 0.01) in patients with a more severe form of the disease as compared to those individuals with mild AD. Additionally, interleukin (IL)-β and interferon γ (IFN-γ), but not interleukin (IL)-6, induced a concentration-dependent increase of S. aureus growth. This effect was not observed with coagulase-negative staphylococci isolated from the skin of AD patients. These findings indicate that inflammatory cytokines such as IL1-β and IFN-γ, can selectively promote S. aureus outgrowth, thus subverting the composition of the healthy skin microbiome. Moreover, biofilm production by S. aureus plays a relevant role in further supporting chronic colonization and disease severity, while providing an increased tolerance to antimicrobials

Urine culture doubtful in determining etiology of diffuse symptoms among elderly individuals: a cross-sectional study of 32 nursing homes

Background: The high prevalence of bacteriuria in elderly individuals makes it difficult to know if a new symptom is related to bacteria in the urine. There are different views concerning this relationship and bacteriuria often leads to antibiotic treatments. The aim of this study was to investigate the relationship between bacteria in the urine and new or increased restlessness, fatigue, confusion, aggressiveness, not being herself/himself, dysuria, urgency and fever in individuals at nursing homes for elderly when statistically considering the high prevalence of asymptomatic bacteriuria in this population.\ud \ud Methods: In this cross-sectional study symptoms were registered and voided urine specimens were collected for urinary cultures from 651 elderly individuals. Logistic regressions were performed to evaluate the statistical correlation between bacteriuria and presence of a symptom at group level. To estimate the clinical relevance of statistical correlations at group level positive and negative etiological predictive values (EPV) were calculated.\ud \ud Results: Logistic regression indicated some correlations at group level. Aside from Escherichia coli in the urine and not being herself/himself existing at least one month, but less than three months, EPV indicated no clinically useful correlation between any symptoms in this study and findings of bacteriuria.\ud \ud Conclusions: Urinary cultures provide little or no useful information when evaluating diffuse symptoms among elderly residents of nursing homes. Either common urinary tract pathogens are irrelevant, or urine culture is an inappropriate test

Anticoagulation for non-valvular atrial aibrillation – towards a new beginning with ximelagatran

OBJECTIVES: Ximelagatran is a novel oral direct thrombin inhibitor. It has favorable pharmacodynamic properties, with a broad therapeutic range without the need for anticoagulation monitoring. We aimed to discover whether ximelagatran offers a genuine future replacement to warfarin for patients in persistent atrial fibrillation (AF). MATERIALS AND METHODS: We provide an evidence-based review of the relative merits and disadvantages of warfarin and aspirin. We subsequently present an overview of the evidence for the utility of ximelagatran in the treatment of AF. RESULTS: Adjusted dose warfarin is recommended over aspirin for patients in AF at high risk of future stroke. Some of this benefit is partially offset by the higher bleeding risks associated with warfarin therapy. The SPORTIF III and V studies have shown that ximelagatran is not inferior to warfarin in the prevention of all strokes in patients with AF (both persistent and paroxysmal). This benefit was partially offset by the finding of a significant elevation of liver transaminases (>3 × normal) in 6% of patients. CONCLUSIONS: Current data would suggest that ximelagatran might represent a future alternative to warfarin. The lack of need for anticoagulant monitoring has been partially offset by a need for regular monitoring of liver function. Further data from randomized clinical trials is clearly needed

Risk of malnutrition and health-related quality of life in community-living elderly men and women: The Tromsø study

Purpose To explore the association between risk of malnutrition as well as current body mass index (BMI) and health-related quality of life (HRQoL) in elderly men and women from the general population. Methods In a cross-sectional population survey including 1,632 men and 1,654 women aged 65 to 87 years from the municipality of Tromsø, Norway, we assessed HRQoL by using the EuroQol (EQ-5D) instrument in three risk groups of malnutrition and in different categories of BMI. The Malnutrition Universal Screening Tool (‘MUST’) was used to evaluate the risk of malnutrition. Results We found a significant reduction in HRQoL with an increasing risk of malnutrition, and this was more pronounced in men than in women. The relationship between BMI and HRQoL was dome shaped, with the highest score values in the BMI category being 25–27.5 kg/m2. Conclusions HRQoL was significantly reduced in elderly men and women at risk of malnutrition. The highest HRQoL was seen in moderately overweight individuals

Identification of Novel Genetic Loci Associated with Thyroid Peroxidase Antibodies and Clinical Thyroid Disease

Peer reviewe

Pharmacokinetics, pharmacodynamics and clinical effects of the oral direct thrombin inhibitor ximelagatran in acute treatment of patients with pulmonary embolism and deep vein thrombosis

Introduction: Ximelagatran is a novel, oral direct thrombin inhibitor that is currently being investigated for the prophylaxis and treatment of thromboembolic events. This study evaluated the pharmacokinetics, pharmacodynamics, and clinical effects of melagatran, the active form of ximelagatran, in patients with both deep vein thrombosis (DVT) and pulmonary embolism (PE). Materials and methods: In this open-label study, 12 patients received a fixed dose of 48 mg oral ximelagatran twice daily for 6-9 days. Plasma samples were collected for determination of melagatran concentrations and scintigraphic changes and adverse events were recorded. Results: Peak plasma concentrations of melagatran were attained approximately 2 h after administration of ximelagatran. Melagatran plasma concentration profiles were similar on Days 1, 2, and 6-9. Plasma activated partial thromboplastin time increased following administration of ximelagatran and reached a peak that was approximately twofold higher than the predose activated partial thromboplastin time and correlated with melagatran plasma concentrations (R-2 = 0.69). All but one patient (with malignancy) showed regressed or unchanged lung scintigraphic findings, and six of these demonstrated no, or only minor, perfusion defects at central evaluation after 6-9 days of ximelagatran treatment. Clinical symptoms, including chest pain, dyspnoea, cough, and oedema, and pain in the affected leg, were improved. Ximelagatran was well tolerated with no deaths or severe bleeding events reported during treatment. Conclusion: Treatment with a fixed dose of oral ximelagatran, used without routine coagulation monitoring, showed reproducible pharmacokinetics and pharmacodynamics with a rapid onset of action and promising clinical results in patients with pulmonary embolism