Introduction: Immune checkpoint inhibition has revolutionized the management of metastatic melanoma, including in the final stages of disease progression: because it is well tolerated, some teams do not discontinue it in hopes of slowing disease progression. The risks are that treatment may be continued unnecessarily, causing side effects, and reduce access to specialist palliative care, in addition to increasing the cost of treatment.
Method: We explored the experiences of 10 patients in a university hospital with metastatic melanoma under continued immune checkpoint inhibitors combined with specialist palliative care.
Pneumocystis jirovecii infections occur in patients treated with methotrexate (MTX) because of immunosuppressive effects of this highly potent dihydrofolate reductase (DHFR) inhibitor. Conversely, MTX may act as an anti drug and consequently may exert a selective pressure on this fungus. In this context, we compared the sequences of the gene of isolates obtained from two groups of patients with infections.
View Article and Find Full Text PDFBackground: The orally available kinase inhibitor R-roscovitine has undergone clinical trials against various cancers and is currently under clinical evaluation against Cushing disease and rheumatoid arthritis. Roscovitine displays biological properties suggesting potential benefits in CF: it partially corrects F508del-CFTR trafficking, stimulates the bactericidal properties of CF alveolar macrophages, and displays anti-inflammatory properties and analgesic effects.
Methods: A phase 2 trial study (ROSCO-CF) was launched to evaluate the safety and effects of roscovitine in Pseudomonas aeruginosa infected adult CF patients carrying two CF causing mutations (at least one F508del-CFTR mutation) and harboring a FEV1 ≥40%.
Background: Increasing resistance to antibiotics of Pseudomonas aeruginosa leads to therapeutic deadlock and alternative therapies are needed. We aimed to evaluate the effects of Lactobacillus clinical isolates in vivo, through intranasal administration on a murine model of Pseudomonas aeruginosa pneumonia.
Results: We screened in vitro 50 pulmonary clinical isolates of Lactobacillus for their ability to decrease the synthesis of two QS dependent-virulence factors (elastase and pyocyanin) produced by Pseudomonas aeruginosa strain PAO1.
Strict anaerobes are undeniably important residents of the cystic fibrosis (CF) lung but are still unknowns. The main objectives of this study were to describe anaerobic bacteria diversity in CF airway microbiota and to evaluate the association with lung function. An observational study was conducted during eight months.
View Article and Find Full Text PDFObjectives: Prosthetic vascular graft infection (PVGI) is a very severe disease. We aimed to determine the factors associated with treatment failure.
Methods: Patients admitted to two University Hospitals with PVGI were included in this retrospective study.
Viruses are important agents in lung function deterioration in Cystic Fibrosis (CF). To date, no standard operating procedures (SOPs) have been established to determine which sampling method is the most effective for an optimal virological diagnosis of respiratory viral infections in CF. Here we investigated the performances of two sampling sites, sputum samples versus nasopharyngeal (NP) swabs, for thirty participants from three CF centres presenting an acute respiratory infection.
View Article and Find Full Text PDFNine new human invasive infections caused by the keratinophilic fungi Nannizziopsis obscura have been reported in France since 2004. The patients had variable clinical manifestations, had frequent dissemination, were mainly T-cell immunocompromised, and all originated from sub-Saharan West Africa. Before collection of the isolates, the etiologies of these infections were often misidentified, underscoring the extent of microscopic and cultural polymorphisms.
View Article and Find Full Text PDFBackground: International guidelines recommend rifampin-based combinations for staphylococcal prosthetic valve endocarditis (PVE). However, no robust clinical data support this recommendation, and rifampin tolerability is an issue. We aimed to evaluate the impact of rifampin for the treatment of staphylococcal PVE.
View Article and Find Full Text PDFInfectious myositis is a rare condition that can be caused by bacteria, viruses, parasites or fungi. Muscle pain or weakness are symptoms shared by all type of myositis. Diagnosis is made on clinical presentation: fever and poor general state is found in bacterial myositis, diffuse muscle pain with flu-like symptoms in viral causes, eosinophilia and a tropical travel history can be related to parasitic etiology, and immunocompromising condition suggests fungal infection.
View Article and Find Full Text PDFThe spreading of antibiotic resistance is a major public health issue, which requires alternative treatments to antibiotics. Lactobacilli have shown abilities to prevent pneumonia in clinical studies when given by oral route, certainly through the gut-lung axis involvement. Rationally, respiratory administration of lactobacilli has been developed and studied in murine model, to prevent from respiratory pathogens.
View Article and Find Full Text PDFIntroduction: pulmonary infections are the primary cause of morbi-mortality in patients with cystic fibrosis (CF). In this cohort study, the objective was to identify candidate biomarkers of infection within the airway microbiota.
Methods: A 3-year prospective multicentre study (PYOMUCO study) was conducted in Western France and included patients initially free for at least 1 year.
Objectives: We aimed to characterize diagnosis, management, and outcome of Mycobacterium tuberculosis prosthetic joint infections (PJI).
Methods: Cases of M. tuberculosis PJI documented in 7 referral French centers were retrospectively reviewed.
Introduction: Behçet disease (BD) is a systemic vasculitis involving vessels from any size with various clinical features. Most BD cases are multifactorial and associated with the HLA B51 antigen. In rare and severe early onset cases, dominant Mendelian transmission has been linked to mutations in the TNFAIP3 gene encoding A20.
View Article and Find Full Text PDFBackground: The objective was to evaluate concordance between 2002 American-European Consensus Group (AECG) and 2016 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) classification criteria for primary Sjögren's syndrome (pSS) and to assess how salivary gland ultrasonography (SGUS) might improve the classification of patients.
Methods: Patients with suspected pSS underwent a standardised evaluation, including SGUS, at inclusion into the single-centre Brittany DIApSS cohort. Agreement between the two criteria sets was assessed using Cohen's κ coefficient.
Although bacteria have historically been considered to play a major role in cystic fibrosis (CF) airway damage, a strong impact of respiratory viral infections (RVI) is also now recognized. Emerging evidence confirms that respiratory viruses are associated with deterioration of pulmonary function and exacerbation and facilitation of bacterial colonization in CF patients. The aim of this review is to provide an overview of the current knowledge on respiratory viruses in CF airways, to discuss the resulting inflammation and RVI response, to determine how to detect the viruses, and to assess their clinical consequences, prevalence, and interactions with bacteria.
View Article and Find Full Text PDFObjectives: Early detection of Pseudomonas aeruginosa lung positivity is a key element in cystic fibrosis (CF) management. PCR has increased the accuracy of detection of many microorganisms. Clinical relevance of P.
View Article and Find Full Text PDF(R)-Roscovitine, a pharmacological inhibitor of kinases, is currently in phase II clinical trial as a drug candidate for the treatment of cancers, Cushing's disease and rheumatoid arthritis. We here review the data that support the investigation of (R)-roscovitine as a potential therapeutic agent for the treatment of cystic fibrosis (CF). (R)-Roscovitine displays four independent properties that may favorably combine against CF: (1) it partially protects F508del-CFTR from proteolytic degradation and favors its trafficking to the plasma membrane; (2) by increasing membrane targeting of the TRPC6 ion channel, it rescues acidification in phagolysosomes of CF alveolar macrophages (which show abnormally high pH) and consequently restores their bactericidal activity; (3) its effects on neutrophils (induction of apoptosis), eosinophils (inhibition of degranulation/induction of apoptosis) and lymphocytes (modification of the Th17/Treg balance in favor of the differentiation of anti-inflammatory lymphocytes and reduced production of various interleukins, notably IL-17A) contribute to the resolution of inflammation and restoration of innate immunity, and (4) roscovitine displays analgesic properties in animal pain models.
View Article and Find Full Text PDFPost-sternotomy mediastinitis, a nosocomial infection mostly caused by staphylococci, can be life-threatening. A case of mediastinitis due to Finegoldia magna after a coronary artery bypass graft surgery was reviewed. Although this bacterium is difficult to be isolated from routine blood cultures, a F.
View Article and Find Full Text PDFBackground: Pseudomonas aeruginosa is an opportunistic pathogen that significantly increases morbidity and mortality in nosocomial infections and cystic fibrosis patients. Its pathogenicity especially relies on the production of virulence factors or resistances to many antibiotics. Since multiplication of antibiotic resistance can lead to therapeutic impasses, it becomes necessary to develop new tools for fighting P.
View Article and Find Full Text PDF