Can radiomics improve the prediction of metastatic relapse of myxoid/round cell liposarcomas?

European Radiology - The strongest adverse prognostic factor in myxoid/round cell liposarcomas (MRC-LPS) is the presence of a round cell component above 5% within the tumor bulk. Its identification...     

Massive hemolysis and acute mitral insufficiency one year following mitral valve repair. Apropos of a case

The authors report a case of massive haemolytic anaemia with acute mitral valve regurgitation and left cardiac failure, which occurred one year after surgical reconstruction of the mitral valve for rupture of smaller leaflet chordae. Anaemia, mitral regurgitation and cardiac failure disappeared after mitral valve replacement, using a Carpentier Edwards No. 29 valve. Haemolytic anaemia following mitral valve reconstruction is exceptional. It seems to be due to the suture material lying in a turbulent regurgitation stream when mitral incompetence develops again.     

Thrombosis and thrombolysis in unstable angina

Pathophysiology of unstable angina involves spasm, plaque rupture, activation of platelets, and coagulation. The incidence and frequency of intracoronary thrombus formation are presently under active assessment in order to establish the potential benefit of thrombolytic therapy. A preliminary study was conducted in patients admitted in our coronary care unit for unstable angina with typical clinical and electrocardiographic criteria and with early coronary angiogram. After exclusion of 4 patients with left main coronary stenosis or contraindications for thrombolysis, 16 patients received thrombolytic infusion and 14 underwent a second coronary angiogram. Seven patients had an intracoronary thrombus (6 nonocclusive, 1 occlusive) and at the second angiogram only 3 nonocclusive thrombi were modified (1 disappeared, 2 were reduced). Moreover, the quantitative Coronary Angiography Analysis System (CAAS) in the 11 cases suitable for analysis did not show any significant changes, especially in the Ambrose type IIB lesions. In-hospital clinical outcome was not influenced by thrombolytic therapy (5 ischemic recurrences, 1 fatal myocardial infarction, 4 emergency and 4 elective revascularization procedures). This short series is in agreement with the literature data. Only one third of patients with active unstable angina remains refractory to conventional therapy. The transient benefit of thrombolysis is limited to patients with demonstrated intracoronary thrombi. Clinical or angiographic improvement are not always in correlation and until now do not seem able to prevent short-term recurrences or the need for revascularization procedures.     

Clinical characterization of imuthiol

Imuthiol is a nontoxic agent recruting and regulating T cells. Phase III studies in chronic bronchitis and bronchiectasis showed that immune functions were restored to normal, or near normal values. Cure was obtained in rheumatoid arthritis, tuberculosis and chronic infections in the elderly. Imuthiol is an effective agent for the treatment of syndromes and disease states where the underlying defect is a T-cell deficiency or dysfunction.     

Use of an automated multiple-locus, variable-number tandem repeat-based method for rapid and high-throughput genotyping of Staphylococcus aureus isolates

Fast and reliable genotyping methods that allow real-time epidemiological surveillance would be instrumental to monitoring of the spread of methicillin-resistant Staphylococcus aureus. We describe an automated variable-number tandem repeat-based method for the rapid genotyping of Staphylococcus aureus. Multiplex PCR amplifications with eight primer pairs that target gene regions with variable numbers of tandem repeats were resolved by microcapillary electrophoresis and automatically assessed by cluster analysis. This genotyping technique was evaluated for its discriminatory power and reproducibility with clinical isolates of various origins, including a panel of control strains previously characterized by several typing methods and collections from either long-term carriers or defined nosocomial outbreaks. All steps of this new procedure were developed to ensure a rapid turnaround time and moderate cost. The results obtained suggest that this rapid approach is a valuable tool for the genotyping of S. aureus isolates in real time.     

Outer membrane protein A renders dendritic cells and macrophages responsive to CCL21 and triggers dendritic cell migration to secondary lymphoid organs

Outer membrane protein A (OmpA) is a class of bacterial cell wall protein that is immunogenic without adjuvant. As specific immune responses are initiated in the lymph nodes (LN, we analyzed the effect of the OmpA from Klebsiella pneumoniae (KpOmpA) onchemokine/ chemokine receptor expression by APC and on cell migration to the LN. Upon contact with KpOmpA, human immature DC and macrophages acquire CCR7 expression and responsiveness to CCL21. In parallel, CCR1 and CCR5 expression is down-regulated and CXCL8, CCL2, CCL3 and CCL5 production is up-regulated. Mice injected subcutaneously with KpOmpA present a transient inflammatory reaction at the site of injection accompanied by an enlargement of the draining LN with a higher proportion of DC and macrophages. Lastly, when exposed to KpOmpA prior injection, DC but not macrophages migrate to the draining LN. In conclusion, KpOmpA confers a migratory phenotype to DC and triggers their migration to the regional LN. This property contributes to explain how innate cells initiate adaptive immune response upon recognition of conserved bacterial components and also why OmpA is immunogenic in the absence of adjuvant.     

Autoimmune diseases in myelodysplastic syndrome favors patients survival: A case control study and literature review

Background

We conducted a monocentric retrospective study of patients with myelodysplastic syndromes (MDS) and autoimmune or inflammatory disorders (AIMs) and a literature review. We analyzed the association with subgroups of the WHO 2016 MDS classification and patient's survival in a case control study. Risk factors associated with survival were analyzed by uni- and multivariate analysis.

Peroxisome proliferator-activated receptor gamma activators affect the maturation of human monocyte-derived dendritic cells

Peroxisome proliferator-activated receptor gamma (PPARgamma ), a member of the nuclear receptor superfamily, has recently been described as a modulator of macrophage functions and as an inhibitor of T cell proliferation. Here, we investigated the role of PPARgamma in dendritic cells (DC), the most potent antigen-presenting cells. We showed that PPARgamma is highly expressed in immature human monocyte-derived DC (MDDC) and that it may affect the immunostimulatory function of MDDC stimulated with lipopolysaccharide (LPS) or via CD40 ligand (CD40L). We found that the synthetic PPARgamma agonist rosiglitazone (as well as pioglitazone and troglitazone) significantly increases on LPS- and CD40L-activated MDDC, the surface expression of CD36 (by 184% and 104%, respectively) and CD86 (by 54% and 48%), whereas it reduces the synthesis of CD80 (by 42% and 42%). Moreover, activation of PPARgamma resulted in a dramatic decreased secretion of the Th1-promoting factor IL-12 in LPS- and CD40L-stimulated cells (by 47% and 62%), while the production of IL-1beta, TNF-alpha, IL-6 and IL-10 was unaffected. Finally, PPARgamma ligands down-modulate the synthesis of IFN-gamma -inducible protein-10 (recently termed as CXCL10) and RANTES (CCL5), both chemokines involved in the recruitment of Th1 lymphocytes (by 49% and 30%), but not the levels of the Th2 cell-attracting chemokines,macrophage-derived chemokine (CCL22) and thymus and activation regulated chemokine (CCL17), in mature MDDC. Taken together, our data suggest that activation of PPARgamma in human DC may have an impact in the orientation of primary and secondary immune responses by favoring type 2 responses.     

Generation of potent T(h)1 responses from patients with lymphoid malignancies after differentiation of B lymphocytes into dendritic-like cells

Dendritic cells (DC) are a group of potent antigen-presenting cells (APC) specialized for initiating T cell immune responses. They originate from the bone marrow and upon stimulation with bacterial products, cytokines or CD40 ligation they acquire the ability to migrate to the secondary lymphoid organs. In vitro DC can be generated from human CD34(+) bone marrow cells and CD14(+) peripheral blood monocytes after culture with different cytokine combinations. Since most leukemic cells and tumors in general are devoid of APC capacities, various strategies have been used to increase their recognition and confer the capacity of antigen presentation on them. Because of our interest in the design of vaccine immunotherapy protocols for the adjuvant treatment of patients with lymphoid malignancies (LM), we chose to explore the capacity of human acute lymphoblastic leukemia, chronic lymphocytic leukemia and plasma cell leukemia to differentiate into cells with APC and DC features. Our results among a sample of 10 patients demonstrate that such approach is feasible. Leukemic cells could be induced in the presence of IL-4 and CD40L to exhibit a DC morphology with a phenotype of mature DC-like cells. They could also induce a potent proliferative response in naive CD4(+) T cells. In addition, they expressed chemokine receptor CCR7 and CD62L, and could drive T cells towards a T(h)1 response with secretion of IFN-gamma. Our strategy leading to increased LM cell immunogenicity may have potential clinical applications and LM appear to be attracting candidates for adjuvant vaccination and adoptive immunotherapy.