Pathogenesis of antiphospholipid syndrome: recent insights and emerging concepts

Introduction: Even though our understanding of the antiphospholipid syndrome (APS) has improved tremendously over the last decades, we are still not in a position to replace symptomatic anticoagulation by pathogenesis based causal treatments.

Areas covered: Recent years have provided further insights into pathogenetically relevant mechanisms. These include a differentiation of pathogenic subtypes of antiphospholipid antibodies (aPL), novel mechanisms modulating disease activity, for example, extracellular vesicles and microRNA, and novel players in pathogenesis, for example, neutrophils and neutrophil extracellular traps (NETs).

Expert commentary: It is evident that aPL induce a proinflammatory and procoagulant state and recent data suggest that different aPL species activate different signaling pathways which sometimes converge into a common cellular response. This implies that presence of more than one aPL species may disproportionally increase the risk for the major manifestations of APS, that is, thrombosis and fetal loss. Further delineation of the pathogenic mechanisms will hopefully provide clues to causal rather than symptomatic treatments of APS.     

Interpretation of gas-blood ratio inP O 2polarography

Summary The differences inP _{O 2}readings between gas and blood were studied with a Clark-type electrode in the range of 38.5 to 713 mm HgP _{O 2}.The tonometered blood samples were taken in two different ways. The results showed that the gas-blood ratior _b(equilibrating gasP _{O 2}reading/equilibrated bloodP _{O 2}reading) depended not only on the sampling method but also on theP _{O 2}range: it varied from 1.005 to 1.032 for aP _{O 2}of 96.5 mm Hg, and from 1.040 to 1.081 for aP _{O 2}of 713 mm Hg according to the sampling procedure.A theoretical analysis demonstrated that the variation ofr _bwith the bloodP _{O 2}can be attributed to the influence of the degree of oxygen saturation of the hemoglobin on theP _{O 2}gradient existing in the blood diffusion boundary layer adhering to the electrode membrane.This work was supported by grants from the High Authority of the European Coal and Steel Community and from the Fonds de la Recherche Scientifique Médicale, Belgium.     

Magnesium in Obesity,Metabolic Syndrome,and Type 2 Diabetes

Magnesium (Mg²⁺) deficiency is probably the most underestimated electrolyte imbalance in Western countries. It is frequent in obese patients, subjects with type-2 diabetes and metabolic syndrome, both in adulthood and in childhood. This narrative review aims to offer insights into the pathophysiological mechanisms linking Mg²⁺ deficiency with obesity and the risk of developing metabolic syndrome and type 2 diabetes. Literature highlights critical issues about the treatment of Mg²⁺ deficiency, such as the lack of a clear definition of Mg²⁺ nutritional status, the use of different Mg²⁺ salts and dosage and the different duration of the Mg²⁺ supplementation. Despite the lack of agreement, an appropriate dietary pattern, including the right intake of Mg²⁺, improves metabolic syndrome by reducing blood pressure, hyperglycemia, and hypertriglyceridemia. This occurs through the modulation of gene expression and proteomic profile as well as through a positive influence on the composition of the intestinal microbiota and the metabolism of vitamins B1 and D.     

Kinder und Jugendliche in der COVID-19-Pandemie – zur besonderen Betroffenheit einer vermeintlichen „low risk group“

Bundesgesundheitsblatt - Gesundheitsforschung - Gesundheitsschutz -     

Distinct immunopathological mechanisms of EBV-positive and EBV-negative posttransplant lymphoproliferative disorders

EBV-positive and EBV-negative posttransplant lymphoproliferative disorders (PTLDs) arise in different immunovirological contexts and might have distinct pathophysiologies. To examine this hypothesis, we conducted a multicentric prospective study with 56 EBV-positive and 39 EBV-negative PTLD patients of the K-VIROGREF cohort, recruited at PTLD diagnosis and before treatment (2013–2019), and compared them to PTLD-free Transplant Controls (TC, n = 21). We measured absolute lymphocyte counts (n = 108), analyzed NK- and T cell phenotypes (n = 49 and 94), and performed EBV-specific functional assays (n = 16 and 42) by multiparameter flow cytometry and ELISpot-IFNγ assays (n = 50). EBV-negative PTLD patients, NK cells overexpressed Tim-3; the 2-year progression-free survival (PFS) was poorer in patients with a CD4 lymphopenia (CD4⁺<300 cells/mm³, p <  .001). EBV-positive PTLD patients presented a profound NK-cell lymphopenia (median = 60 cells/mm³) and a high proportion of NK cells expressing PD-1 (vs. TC, p = .029) and apoptosis markers (vs. TC, p < .001). EBV-specific T cells of EBV-positive PTLD patients circulated in low proportions, showed immune exhaustion (p = .013 vs. TC) and poorly recognized the N-terminal portion of EBNA-3A viral protein. Altogether, this broad comparison of EBV-positive and EBV-negative PTLDs highlight distinct patterns of immunopathological mechanisms between these two diseases and provide new clues for immunotherapeutic strategies and PTLD prognosis.     

The prevalence of serological markers for the human immunodeficiency virus and the hepatitis B virus in a psychiatric hospital

OBJECTIVES: To estimate the prevalence of antibodies to human immunodeficiency virus (HIV), antibodies to hepatitis B core antigen (anti-HBc), hepatitis B surface antigen (HBsAg), and antibodies to delta virus (anti-DV). DESIGN: Cross-sectional (prevalence) study. A non-proportional (stratified by length of stay) random sample of 20% of admitted patients was selected. CLINICAL SETTING: The Hospital Psiquiátrico Nuestra Se?ora de Montserrat (Sant Boi de Llobregat, Barcelona, Spain) admits about 670 patients in its short-term, rehabilitation (mid-term) and long-term wards. SUBJECTS: 139 patients were selected: 91% were males, mean age was 55 years, and 10% belonged to an HIV risk group; mean length of hospitalization since last discharge was 13 years. MEASUREMENTS: Blood samples were drawn in October, 1988. Anti-HBc, HBsAg and anti-DV were determined by competitive enzyme immunoassay (EIA). Anti-HIV-1 were determined by sandwich EIA; negativity of results with high absorbency but below the cut-off point was confirmed by Western blot. RESULTS: None of the sampled patients had circulating anti-HIV-1 antibodies. Four cases showing high absorbency (below the "cut-off" point) were ruled out by Western-blot. Overall, the prevalence of anti-HBc was 52.8% (54.4% in long-term wards, 35.0% in mid-term wards, and 13.8% in short-term wards). The prevalence of HBsAg was 2.3%, of anti-DV 1.5%, and of HDAg 0%. CONCLUSIONS: Prevalence of anti-HIV is null in the studied institution. Current efforts to prevent HIV infection must continue; a hepatitis B vaccination program is highly warranted among patients and professionals of the studied hospital.     

Reversible tonsillar prolapse in vein of Galen aneurysmal malformations: report of eight cases and pathophysiological hypothesis

We report eight cases of vein of Galen aneurysmal malformation (VGAM) assoicated with a Chiari type I malformation. In four cases magnetic resonance imaging (MRI) or computed tomography performed in the neonatal period did not demonstrate the posterior fossa anomaly, which appeared on later scans. In the other cases the MRI was performed in infancy and the anomaly was already present. We compared the venous phases of the posterior fossa angiograms and the MRI in these patients. In all eight cases, the angiograms showed a reflux in the cerebellar veins, via the petrous vein, associated with a uni-or bilateral stenosis or thrombosis of the distal posterior dural sinuses. Furthermore, in two cases the posterior fossa returned to normal on MRI following endovascular treatment, while in three cases the herniation of the cerebellar tonsils decreased after the embolization. Tonsillar prolapse becomes irreversible when the venous outlet is incapable of taking the flow even when the VGAM has been treated adequately. In eight additional cases of VGAM for which MRI and angiogram studies were available and in which stenosis or thrombosis of posterior dural sinuses was present without tonsillar prolapse, no reflux into the cerebellar veins was shown. We suggest that the posterior fossa hydrovenous congestion is a result of inadequate venous drainage and that the tonsillar descent is reversible if adequate venous drainage is reconstituted following therapeutic embolization of the fistula. Tonsillar prolapse is not a consequence of mass or raised intraventricular pressure. Our observation suggests that in some other conditions, the Chiari I malformations may be secondary to early hydrovenous dysfunction of the posterior fossa.     

Prenatal and postnatal transplantation of hematopoietic stem cells in children with primary immunodeficiency

Primary immunodeficiencies are inherited diseases characterized by impaired immune responses. In case of severe impairment of immunity bone marrow transplantation is the only therapeutic option. The molecular defect is known for several primary immunodeficiencies allowing prenatal diagnosis. This paper summarizes the clinical experience treating these pathologies by bone marrow transplantation.     

Wunderlich's syndrome in a patient on hemodialysis with acquired cystic kidney disease. A report of a new case

We report a new case of Wunderlich's syndrome (spontaneous perirenal hematoma) in a patient with chronic renal failure undergoing hemodialysis secondary to acquired renal cystic disease. The literature relative to this condition is review.