Authorship Contributions: AH, CB were in charge of the patients and provided the clinical samples. MD, DB and DL performed the coagulation tests. TS, CC, IP and PJL designed and performed the in ...vitro and in vivo experiments.
Infantile myofibromatosis: A series of 28 cases Mashiah, Jacob, MD, MHA; Hadj-Rabia, Smail, MD, PhD; Dompmartin, Anne, MD, PhD ...
Journal of the American Academy of Dermatology,
08/2014, Letnik:
71, Številka:
2
Journal Article
Recenzirano
Background Infantile myofibromatosis (IM) is a rare disorder of fibroblastic/myofibroblastic proliferation in children. Objectives We sought to document common and unusual characteristics of patients ...with IM. Methods This was a retrospective study of 28 children diagnosed with histopathologically confirmed IM between 1992 and 2012. Epidemiologic, clinical, and treatment data were reviewed. Results IM was more frequent in boys (60.8%). Skin lesions were congenital in 64.3% of cases. The solitary form accounted for 50% of cases. Most nodules were painless, arising in cutaneous or subcutaneous tissue. The multicentric form accounted for 39% of cases; the skin, subcutaneous tissue, or muscle was involved in 97.8% of cases, and the bones in 50% of cases. The generalized form had a mortality rate of 33% (one-third of cases). Multicentric and generalized forms regressed spontaneously; severe local complications were observed, and late recurrent nodules developed in a few cases. Limitations The retrospective review and the ascertainment of patients (from the departments of obstetrics and pediatrics) may have introduced bias in the analysis of severity of the different forms of IM. Conclusion The diagnosis of IM must be confirmed histopathologically because the clinical presentation can be misleading. The prognosis is usually good, although local morbidity can occur. The generalized and multicentric forms merit long-term follow-up.
Pituitary stalk interruption syndrome (PSIS) may induce an isolated growth hormone (GH) deficiency or multiple hypothalamic-pituitary (HP) deficiencies. Patients with multiple HP deficiencies, ...primarily those with adrenocorticotropin (ACTH) deficiency, are at increased risk of morbidity and mortality. Our objective was to identify the factors influencing each symptom and the MRI features of the syndrome to enhance its diagnosis and genetic analysis.
This study was a retrospective, single-center, case-cohort study of 53 patients with PSIS who had reached pubertal age.
Patients were classified as having an isolated GH deficiency (n = 24, Group 1) or HP deficiencies (n = 29, Group 2); of these, 19 had complete HP deficiency, and 10 had GH deficiency associated with TSH (n = 4), TSH and ACTH (n = 3), TSH and gonadotropin (n = 1) deficiencies or amenorrhea (n = 2). The following features were less frequent in Group 1 than in Group 2: breech presentation (4% vs 35%, P = 0.008), hypoglycemia (0% vs 59%, P<0.00001), micropenis (13% vs 69%, P<0.003), hypothalamic origin (0% vs 52%, P<0.000001), ophthalmic malformation (8% vs 38%, P<0.02) and psychomotor delay (0% vs 31%, P<0.004). The frequencies of all other malformations were similar in both groups (37% vs 59%). A visible pituitary stalk was characteristic of patients belonging to Group 1 (P<0.0002). The GH peak was greater in Group 1 than in Group 2 (P<0.0003), as was the anterior pituitary height (P = 0.01).
The factors that best discriminate patients with multiple HP deficiencies from those with an isolated GH deficiency are breech presentation, hypoglycemia, and micropenis. No patient with an isolated GH deficiency had psychomotor delay, but associated malformations and/or syndromes, with the exception of ophthalmic disorders, occurred with similar frequencies in both groups. We have also shown that each of the above characteristics is associated with a given HP deficiency and/or malformation/syndrome in the majority of cases.
We retrospectively analysed the data files of 171 adults and 87 children/adolescents with severe haemophilia, except for 14 patients (moderate; minor) (1), to develop a global population ...pharmacokinetic (PK) model for eight factors VIII (FVIII) that could estimate individual PK parameters for targeting the desired level of FVIII activity (FVIII:C); and (2) to compare half-life (HL) in patients switching from a standard half-life (SHL) to an extended half-life (EHL) and evaluate the relevance of the switch. One-stage clotting assay for the measurement of FVIII activity (FVIII:C, IU/mL) was used for population PK modelling. The software, Monolix version 2019R1, was used for non-linear mixed-effects modelling. A linear two-compartment model best described FVIII:C. The estimated PK parameters (between-subject variability) were: 2640 mL (23.2%) for volume of central compartment (V1), 339 mL (46.8%) for volume of peripheral compartment (V2), 135 mL/h for Q (fixed random effect), and 204 mL/h (34.9%) for clearance (Cl). Weight, age, and categorical covariate EHL were found to influence Cl and only weight for V1. This model can be used for all of the FVIII cited in the study. Moreover, we demonstrated, in accordance with previous studies, that Elocta had longer half-life (EHL) than SHL (mean ratio: 1.48) as compared to Advate, Factane, Kogenate, Novoeight, and Refacto.
Les déficits en protéine S d’origine acquise comme ceux d’origine constitutionnelle exposent à un risque thrombotique. Les déficits acquis, en lien avec la présence d’un auto-anticorps spécifique ...dirigé contre la protéine S, sont susceptibles d’entraîner des déficits sévères. Ils peuvent être responsables de thromboses, mais aussi d’une symptomatologie clinique particulière de type purpura nécrotique extensif, qui constitue une urgence diagnostique et thérapeutique, souvent associé à d’autres thromboses profondes et à une coagulation intravasculaire disséminée biologique.
Le contexte étiologique est le plus souvent post-infectieux, après une varicelle ou d’autres infections virales ou bactériennes. Le diagnostic biologique doit être exécuté rapidement : d’une part un hémogramme et un bilan d’hémostase pour mettre en évidence les signes biologiques de consommation, et d’autre part un dosage spécifique de l’activité de la protéine S. Si les résultats font suspecter un auto-anticorps dirigé contre la protéine S, sa mise en évidence par méthode Elisa devra tout de suite compléter le bilan.
La prise en charge thérapeutique est aussi urgente. Une anticoagulation efficace doit être instaurée le plus rapidement possible, associée à des transfusions de plasma frais congelé pour corriger la consommation. Les échanges plasmatiques et les immunoglobulines intraveineuses permettent ensuite d’éradiquer l’auto-anticorps.
Both acquired and inherited protein S deficiencies expose patients to the risk of thrombosis. Acquired deficiency, linked to the presence of a specific autoantibody directed against protein S, can lead to a severe disease. They may be responsible for thrombosis, but also for extensive necrotic purpura, which constitutes a medical emergency. It is often associated with disseminated intravascular coagulation and also deep venous thrombosis. The etiology is usually post-infectious, following chickenpox or other viral or bacterial infections.
Biological diagnosis is an emergency. It must include a hemogram and hemostasis tests to reveal disseminated intravascular coagulation, and to measure protein S activity. If the results suggest the presence of autoantibodies to protein S, the Elisa method should be used quickly.
Therapeutic management is also urgent. Effective anticoagulation must be introduced as quickly as possible, combined with transfusions of fresh frozen plasma to correct coagulation factors. Plasma exchange and intravenous immunoglobulins are then used to eradicate the autoantibody.
Microbial nucleic acid recognition serves as the major stimulus to an antiviral response, implying a requirement to limit the misrepresentation of self nucleic acids as non-self and the induction of ...autoinflammation. By systematic screening using a panel of interferon-stimulated genes we identify two siblings and a singleton variably demonstrating severe neonatal anemia, membranoproliferative glomerulonephritis, liver fibrosis, deforming arthropathy and increased anti-DNA antibodies. In both families we identify biallelic mutations in DNASE2, associated with a loss of DNase II endonuclease activity. We record increased interferon alpha protein levels using digital ELISA, enhanced interferon signaling by RNA-Seq analysis and constitutive upregulation of phosphorylated STAT1 and STAT3 in patient lymphocytes and monocytes. A hematological disease transcriptomic signature and increased numbers of erythroblasts are recorded in patient peripheral blood, suggesting that interferon might have a particular effect on hematopoiesis. These data define a type I interferonopathy due to DNase II deficiency in humans.
Introduction
Emicizumab (Hemlibra®) recently became available and requires an adaptation for managing bleeding, suspected bleeding and emergency or scheduled invasive procedures in haemophilia A ...patients with inhibitor. This implicates a multidisciplinary approach and redaction of recommendations for care that must be regularly adapted to the available data.
Aim
The following text aims to provide a guide for the management of people with haemophilia A with inhibitor treated with emicizumab in case of bleeding or invasives procedures.
Methods
The French network on inherited bleeding disorders (MHEMO), the French Reference Centre on Haemophilia (CRH), in collaboration with the French Working Group on Perioperative Haemostasis (GIHP) have been working together to make proposals for the management of these situations.
Results
Haemostatic treatment and other medications should be given stepwise, according to the severity and location of the bleeding or the risk of bleeding of the procedure as well as the haemostatic response obtained at each step in order to ensure an optimal benefit/risk ratio.
Conclusion
The lack of data means that it is only possible to issue proposals rather than recommendations.
Emicizumab and asparaginase, A first experience to share Goubeau, Laurie; Bally, Cécile; Borgel, Delphine ...
Haemophilia : the official journal of the World Federation of Hemophilia,
March 2024, Letnik:
30, Številka:
2
Journal Article
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