Anti-PF4 VITT antibodies are oligoclonal and variably inhibited by heparin.

BACKGROUND: COVID-19 vaccines have been associated with a rare thrombotic and thrombocytopenic reaction, Vaccine-induced immune thrombotic thrombocytopenia (VITT) characterized by platelet-activating anti-PF4 antibodies. This study sought to assess clonality of VITT antibodies and evaluate their characteristics in antigen-based and functional platelet studies. METHODS: Anti-PF4 antibodies were isolated from five patients with VITT secondary to ChAdOx1 nCoV-19 (n=1) or Ad26.COV2.S (n=4) vaccination. For comparative studies with heparin-induced thrombocytopenia (HIT), anti-PF4 antibodies were isolated from one patient with spontaneous HIT, another with "classical" HIT, and two patients with non-pathogenic (non-platelet activating) anti-PF4 antibodies. Isolated antibodies were subject to ELISA and functional testing, and mass spectrometric evaluation for clonality determination. RESULTS: All five VITT patients had oligoclonal anti-PF4 antibodies (3 monoclonal, one bi- and one tri-clonal antibodies), while HIT anti-PF4 antibodies were polyclonal. Notably, like VITT antibodies, anti-PF4 antibodies from a spontaneous HIT patient were monoclonal. The techniques employed did not detect non-pathogenic anti-PF4 antibodies. The ChAdOx1 nCoV-19-associated VITT patient made an excellent recovery with heparin treatment. In vitro studies demonstrated strong inhibition of VITT antibody-induced platelet activation with therapeutic concentrations of heparin in this and one Ad26.COV2.S-associated VITT patient. Oligoclonal VITT antibodies with persistent platelet-activating potential were detected at 6 and 10 weeks after acute presentation in two patients tested. Two of the 5 VITT patients had recurrence of thrombocytopenia and one patient had focal seizures several weeks after acute presentation. CONCLUSION: Oligoclonal anti-PF4 antibodies mediate VITT. Heparin use in VITT needs to be further studied.

[Peyronie's disease-often a disabling disease for sexually active men]. / Maladie de la peyronie: une maladie invalidante pour tes hommes sexuettement actifs.

Peyronie's disease is an acquired penile condition characterized by fibrous plaques between the tunica albuginea and the subtunical tissue of the corpora cavernosa. Plaques are considered responsible for the main symptoms: penile pain and deviation. Even though several risk factors and associations with other diseases are known its exact aetiology remains unclear. Most commonly discussed hypotheses are micro traumata, inflammatory and/or ischemic processes. Currently different treatment forms exist raging form systemic or local medical treatment, to physical applications and surgery. All treatment forms are symptom based and evidence based treatment remains difficult to establish. Because conservative treatment is of limited success in many patients especially with severe deviations surgery becomes necessary.

[Results of a dental screening of children in five nursery schools in Codogno (MI), in the 1987/88 school year]. / Risultati dello screening odontoiatrico nell'ambito della popolazione infantile frequentante le cinque scuole materne del comune di Codogno (MI), nell'anno scolastico 1987/88.

Result of a dental screening in the 5 maternal school populations of Codogno (Milan) in the 1987/88 school year. The results of a dental screening performed on 251 pupils from 3 year-old to 5 year-old are reported. The data texted were: oral hygiene degree decayed milk-teeth, decayed permanent teeth, dental and facial anomalies in accordance with WHO classification Geneve 1977.

[Results of a dental screening in a group of students in 3 Codogno (Milan) elementary schools in the 1986-87 school year]. / Risultati dello screening odontoiatrico nell'ambito della popolazione scolastica di tre istituti comunali elementari del comune di Codogno (MI) nell'anno scolastico 1986.87.

The results of a dental screening performed on 582 pupils from 6 year old to 10 year old are presented. The data texted were: oral hygiene degree, decayed milk teeth, decayed permanent teeth, dental and facial anomalies in accordance with W.H.O. classification, Geneve 1977. The classes where pupils brush their teeth at least one time a day, show best oral hygiene conditions than the others.