Tocilizumab therapy reduced intensive care unit admissions and/or mortality in COVID-19 patients.

INTRODUCTION: No therapy has yet proven effective in COVID-19. Tocilizumab (TCZ) in patients with severe COVID-19 could be an effective treatment. METHOD: We conducted a retrospective case-control study in the Nord Franche-Comté Hospital, France. We compared the outcome of patients treated with TCZ and patients without TCZ considering a combined primary endpoint: death and/or ICU admissions. RESULTS: Patients with TCZ (n=20) had a higher Charlson comorbidity index (5.3 [±2.4] vs 3.4 [±2.6], P=0.014), presented with more severe forms (higher level of oxygen therapy at 13L/min vs 6L/min, P<0.001), and had poorer biological findings (severe lymphopenia: 676/mm3 vs 914/mm3, P=0.037 and higher CRP level: 158mg/L vs 105mg/L, P=0.017) than patients without TCZ (n=25). However, death and/or ICU admissions were higher in patients without TCZ than in the TCZ group (72% vs 25%, P=0.002). CONCLUSION: Despite the small sample size and retrospective nature of the work, this result strongly suggests that TCZ may reduce the number of ICU admissions and/or mortality in patients with severe SARS-CoV-2 pneumonia.

[Skin necrosis during long-term fluindione treatment revealing protein C deficiency]. / Nécroses cutanées tardives sous fluindione révélant un déficit en protéine C.

BACKGROUND: Cutaneous necrosis is a rare complication of vitamin K antagonist therapy. It presents as cutaneous hemorrhagic necrosis and usually occurs at the start of treatment. We describe an atypical case of recurrent skin necrosis after two years of treatment with fluindione. CASE REPORT: A 70-year old woman with a history of venous thromboembolism and obesity presented with a large haemorrhagic necrosis of the abdominal wall. She had been treated with fluindione for two years. Genetic protein C deficiency was discovered. Resumption of vitamin K antagonist therapy was followed by recurrence of skin necrosis despite concomitant administration of heparin. Treatment with vitamin K antagonists could not be continued. DISCUSSION: This observation is unusual due to the late onset of skin necrosis. The condition usually begins shortly after initiation of vitamin K antagonist therapy, generally between the third and the sixth day of treatment. It is due to a transient hypercoagulable state in patients with protein C deficiency or, in rare cases, protein S deficiency. This late-onset skin necrosis, occurring many years after initiation of anticoagulant therapy, may be explained by a sudden worsening of pre-existing protein C deficiency due to infectious and iatrogenic factors.

[A cytological, immunophenotypical and cytogenetical study of 136 consecutive cases of B-cell chronic lymphoid hemopathies]. / Etude cytologique, immunophénotypique et cytogénétique d'une série de 136 cas consécutifs d'hémopathies lymphoïdes chroniques à cellules B matures.

A cytological, immunophenotypical and cytogenetical study of 136 chronic B-cell proliferations (93 CLL, 43 B-cell lymphomas) was led in order to precise diagnosis and to characterize and appreciate chromosomal rearrangements. In this series, mainly selected on blood lymphocytosis criteria, B-CLL were twice more frequent than small B-cell lymphomas. Probes used revealed cryptic abnormalities, which remained unknown by conventional cytogenetics (CC). The frequency of clonal abnormalities (CC and FISH) was 74.8% for this series, with 74.4% for lymphomas and 75.3% for CLL, mainly of Binet stage A (69 A, 13 B, 1 C, 10 unspecified). Proportion was 88.4% in A stages and 84.6% in B stages. In CLL, 13q14 cryptic deletions and translocations were widely majority, 14q32 translocations and trisomy 12 being predominant in lymphoma series. Interphase FISH study of non-clonal metaphasic abnormalities with locus-specific probes often revealed unrecognised clones.

Aberrant CD8 expression in B-chronic lymphocytic leukemia: report of five cases.

The expression of T cell-associated antigens on B cell non-Hodgkin lymphoma is rare. We describe 5 cases of B-chronic lymphocytic leukemia (B-CLL) with aberrant expression of CD8 on B cells. These B-CLL presented a typical immunophenotype CD19+, CD23+, FMC7- and CD5+ (except for 1 case) with a monotypic expression of surface immunoglobulin light chain kappa. The CD8 expression was confirmed on B-CLL cells by two-color flow cytometry staining. We could not find coexpression of CD3 or CD4 on B-CLL cells. The clinical implications, the sensitivity to therapy and the prognostic outcome of this aberrant expression remains to be determined.

[Left branch portal vein thrombosis associated with hyperhomocysteinemia]. / Thrombose de la branche gauche de la veine porte associée à une hyperhomocystéinémie.

A 34 year-old man, who was a smoker, was hospitalised because of severe epigastric and right upper quadrant pain. An isolated left branch portal vein thrombosis was diagnosed using ultrasonography and arteriography. Two thrombogenic pathologies were found: i) a latent myeloproliferative syndrome with spontaneous presence of erythroid colony forming unit (CFU-E) in bone marrow culture, normal blood cell count, platelet count and medullogram; ii) a hyperhomocysteinemia associated with low serum folate levels and a methyl tetrahydrofolate reductase mutation. The association of these two factors probably resulted in portal vein thrombosis. This is the first adult case of a portal vein thrombosis associated with hyperhomocysteinemia. Increased homocysteine serum levels could be a previously unrecognized factor for portal vein thrombosis. Homocysteinemia should be systematically investigated in patients with idiopathic portal vein thrombosis since folate supplements could prevent deleterious vascular effects of hyperhomocysteinemia.

Interaction of the two components of leukocidin from Staphylococcus aureus with human polymorphonuclear leukocyte membranes: sequential binding and subsequent activation.

The sequential interaction between the two components S and F of leukocidin from Staphylococcus aureus and the membrane of human polymorphonuclear neutrophils has been investigated in the presence of 1 mM Ca2+. With 125I-labeled components, it has been shown that binding of the F component occurred only after binding of the S component. The kinetic constants of binding of both components were not statistically different (Kd, approximately 5 nM; Bm, approximately 35,000 molecules per cell), and both Hill coefficients were 1. The application of increasing concentrations of leukocidin provoked a dose-dependent secretion of the granule content, as determined by hexosaminidase and lysozyme activity measurements. Furthermore, the separate perfusion of S and F components on human polymorphonuclear neutrophils deposited on a filter induced secretion of the granules content only when the perfusion of the S component preceded that of the F component. We conclude, therefore, that (i) S-component binding is a prerequisite for F-component binding and for subsequent activation of polymorphonuclear neutrophils and (ii) there is a specific binding site for the S component in the plasma membrane.

A structurally novel staphylococcal protein A from the V8 strain.

Protein A from the Staphylococcus aureus strain V8 has a molecular mass about 8000 Da less than that of known proteins A. The corresponding gene was cloned and expressed in Escherichia coli. Sequence analysis of this structurally new protein A revealed that it lacked an IgG-binding domain (58 amino acids), and that it also lacked two octapeptide repetitions located in the membrane/wall attaching region. Contrary to what had been proposed previously, the first translated amino acid is probably not a leucine, but very likely a methionine located 12 residues upstream.