Villumsenhelbo3753

Myrcludex B and Lonafarnib increase therapeutic efficacy in combination with Peg-IFN alfa. In a pilot study, REP 2139 in combination with Peg-IFN alfa induced the clearance of serum HDV RNA and of the HBsAg in about half of 12 treated patients. IMPLICATIONS Long-term therapies with either Myrcludex B or Lonafarnib in combination with Peg-IFN alfa are required to achieve clinical control of CHD. However, with prolonged therapies tolerance becomes a problem; studies are on the way to determine whether Peg-IFN lambda may be better tolerated that Peg-IFN alfa. The promising preliminary data of REP 2139 in combination with Peg-IFN alfa await confirmation of the original pilot study. BACKGROUND Invasive fungal infections (IFI) represent a global issue and affect various patient populations. In recent years, resistant fungal isolates showing increased MICs to azoles or echinocandins have been reported, and their potential clinical impact has been investigated. OBJECTIVES To provide an update on the epidemiology of resistance among fungi (e.g., Candida spp., Aspergillus spp., and Cryptococcus spp.) and offer a critical appraisal of the relevant literature regarding the impact of MICs on clinical outcome in patients with IFI. SOURCES PubMed search with relevant keywords along with personal collection of relevant publications. CONTENT Although antifungal resistance has been associated with a poorer response to antifungal therapy in various studies, other factors such as comorbidities, septic shock and source of infection appear to be key determinants affecting the clinical outcome of patients with IFI. IMPLICATIONS Future international collaborative studies are required to tease out the relative contribution of in vitro antifungal resistance on patient outcomes, thus enabling the optimisation of IFI management. BACKGROUND The use of implanted medical devices is associated with a small but clinically important risk of foreign body infection. A key question is Why do some patients develop chronic infection associated with an implanted device, but most do not? OBJECTIVES The literature on patient-specific risk factors for chronic infections associated with five types of implants was surveyed to glean clues about the etiology of these infections. SOURCES Data were collected from 47 articles through calendar year 2017 for five categories of device-related infections cardiovascular implantable electronic devices (CIEDs), hernia meshes, prosthetic hip and knee joints, prosthetic shoulder joints, and breast implants. CONTENT Important risk factors include immunomodulation/steroid therapy, diabetes, smoking, and renal disease/hemodialysis, findings that point to a critical role of a compromised innate immune response in determining vulnerable subpopulations. IMPLICATIONS A model of biofilm-related device infection is presented that posits defects in the innate immune response both systemically and locally, in the immediate vicinity of an abiotic biomaterial. The limitations of in vitro and animal models of chronic device-related infections are discussed in this context as are implications for research and clinical practice. OBJECTIVES There is increasing evidence that ferritin is a key marker of macrophage activation, but its potential role in influenza infection remains unexplored. Our aim was to assess whether hyperferritinaemia (ferritin ≥500 ng/mL) could be a marker of poor prognosis in hospitalized patients with confirmed influenza A infection. METHODS We prospectively recruited all hospitalized adult patients who tested positive for the influenza A rRT-PCR assay performed on respiratory samples in two consecutive influenza periods (2016-17 and 2017-18). Poor outcome was defined as the presence of at least one of the following respiratory failure, admission to the intensive care unit, or in-hospital mortality. RESULTS Among 494 patients, 68 (14%) developed poor outcomes; 112 patients (23%) had hyperferritinaemia (39/68, 57% in the poor-outcome group versus 73/426, 17% in the remaining patients, p  less then  0.0001). Median serum ferritin levels were significantly higher in the subgroup of patients with poor outcomes (609 ng/mL, range 231-967 versus 217 ng/mL, range 140-394, p  less then  0.0001). selleck chemical In multivariate analysis, hyperferritinaemia was associated with a five-fold increase in the odds ratio of developing poor outcome. After adjusting for classic influenza risk factors, ferritin remained as a significant predictive factor in all exploratory models. Ferritin levels had a good discriminative capacity with an area under the ROC curve of 0.72 (95% confidence interval (CI) 0.65-0.8, p  less then  0.001) and an overall diagnostic accuracy for predicting poor outcome of 79.3% (95%CI 75.4-82.7%). CONCLUSIONS Serum ferritin may discriminate a subgroup of patients with influenza infection who have a higher risk of developing a poor outcome. OBJECTIVES Early diagnosis of adult-onset immunodeficiency associated with neutralizing anti-interferon-gamma autoantibodies (anti-IFNγ Abs) remains difficult given the lack of a distinctive phenotype and a routine test. This study aimed to investigate the determinants of incorrect tentative diagnoses and useful clues for early disease recognition. METHODS This study enrolled adult patients who had unexplained opportunistic infections diagnosed at six hospitals and identified those having neutralizing anti-IFNγ Abs (cases). Demographics, medical history, initial presentations and laboratory data, causative pathogens, tentative diagnoses, and treatment were analyzed and compared between individuals having neutralizing anti-IFNγ Abs (cases) and those without (controls). RESULTS Among the 154 patients enrolled, neutralizing anti-IFN-γ Abs were detected in 50 (71%) of 70 patients with disseminated non-tuberculous mycobacterial infection (dNTM) but not in 84 patients without dNTM. The median time from disease onset to the recognition of dNTM associated with neutralizing anti-IFNγ Abs was 1.6 (range, 0.25-19 y) years. Incorrect tentative diagnoses resulted in the administration of anti-tuberculosis regimens (60%, 30/50), immunosuppressants (48%, 24/50), and systemic chemotherapy (2%, 10/50) to the 50 cases. Multivariate analysis revealed that case patients were more likely than controls to present with multiple bone lesions (adjusted odds ratio [OR], 27.16; 95% CI, 1.21-609.59) and leukocytosis (adjusted OR, 1.48; 95% CI, 1.12-1.95); however, the controls had a higher rate of mycobacterial bloodstream infection (adjusted OR, 0.05; 95% CI 0.00-0.66). CONCLUSIONS The high rate of incorrect tentative diagnoses led to frequent inappropriate management in patients with neutralizing anti-IFNγ Abs, and highlighted the need for increased awareness among clinicians.