Tuberculosis associated thrombocytopenic purpura: effectiveness of antituberculous therapy

Association of immune thrombocytopenic purpura and tuberculosis is a rare condition. In 5 patients presenting with this association, anti-tuberculous therapy was effective on both tuberculosis and thrombocytopenia suggesting a causal relationship between tuberculosis and immune thrombocytopenic purpur

The Transition between Telomerase and ALT Mechanisms in Hodgkin Lymphoma and Its Predictive Value in Clinical Outcomes

International audienceBackground: We analyzed telomere maintenance mechanisms (TMMs) in lymph node samples from HL patients treated with standard therapy. The TMMs correlated with clinical outcomes of patients. Materials and Methods: Lymph node biopsies obtained from 38 HL patients and 24 patients with lymphadenitis were included in this study. Seven HL cell lines were used as in vitro models. Telomerase activity (TA) was assessed by TRAP assay and verified through hTERT immunofluorescence expression; alternative telomere lengthening (ALT) was also assessed, along with EBV status. Results: Both TA and ALT mechanisms were present in HL lymph nodes. Our findings were reproduced in HL cell lines. The highest levels of TA were expressed in CD30−/CD15− cells. Small cells were identified with ALT and TA. Hodgkin and Reed Sternberg cells contained high levels of PML bodies, but had very low hTERT expression. There was a significant correlation between overall survival (p < 10−3), event-free survival (p < 10−4), and freedom from progression (p < 10−3) and the presence of an ALT profile in lymph nodes of EBV+ patients. Conclusion: The presence of both types of TMMs in HL lymph nodes and in HL cell lines has not previously been reported. TMMs correlate with the treatment outcome of EBV+ HL patients

COVID-19 symptoms at hospital admission vary with age and sex: results from the ISARIC prospective multinational observational study

Background: The ISARIC prospective multinational observational study is the largest cohort of hospitalized patients with COVID-19. We present relationships of age, sex, and nationality to presenting symptoms. Methods: International, prospective observational study of 60 109 hospitalized symptomatic patients with laboratory-confirmed COVID-19 recruited from 43 countries between 30 January and 3 August 2020. Logistic regression was performed to evaluate relationships of age and sex to published COVID-19 case definitions and the most commonly reported symptoms. Results: ‘Typical’ symptoms of fever (69%), cough (68%) and shortness of breath (66%) were the most commonly reported. 92% of patients experienced at least one of these. Prevalence of typical symptoms was greatest in 30- to 60-year-olds (respectively 80, 79, 69%; at least one 95%). They were reported less frequently in children (≤ 18 years: 69, 48, 23; 85%), older adults (≥ 70 years: 61, 62, 65; 90%), and women (66, 66, 64; 90%; vs. men 71, 70, 67; 93%, each P &lt; 0.001). The most common atypical presentations under 60 years of age were nausea and vomiting and abdominal pain, and over 60 years was confusion. Regression models showed significant differences in symptoms with sex, age and country. Interpretation: This international collaboration has allowed us to report reliable symptom data from the largest cohort of patients admitted to hospital with COVID-19. Adults over 60 and children admitted to hospital with COVID-19 are less likely to present with typical symptoms. Nausea and vomiting are common atypical presentations under 30 years. Confusion is a frequent atypical presentation of COVID-19 in adults over 60 years. Women are less likely to experience typical symptoms than men

ETUDE DE PATIENTES DE PHENOTYPE TURNERIEN AVEC PRESENCE DE MATERIEL Y (A PROPOS DE 7 CAS (DES BIOL. MED.))

PARIS7-Xavier Bichat (751182101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Syndromes lymphoprolifératifs et immunosuppresseurs

Les syndromes lymphoprolifératifs compliquant l’évolution de pathologies liées à un déficit immunitaire, qu’il soit primitif ou acquis, sont des complications bien identifiées et d’évolution péjorative. Parmi les causes de déficit immunitaire acquis, les traitements immunomodulateurs dans le cadre de pathologies auto-immunes doivent faire l’objet d’observatoires afin de déterminer le rôle respectif des immunosuppresseurs et de la pathologie sous-jacente caractérisée par une stimulation lymphocytaire persistante et un déséquilibre cytokinique. Les syndromes lymphoprolifératifs survenant dans le contexte des greffes d’organe ou de moelle osseuse sont des complications des traitements immunosuppresseurs et probablement de la stimulation antigénique sous-jacente. Leur fréquence varie selon les traitements immunosuppresseurs utilisés, le type d’organe greffé et le statut de l’infection par le virus d’Epstein-Barr (EBV) du receveur. Ces proliférations tumorales développées aux dépens des cellules lymphoïdes du receveur, dérivant de cellules du centre germinatif ou post-centre germinatif, résultent de différents mécanismes de lymphomagenèse. Le rôle de l’EBV conférant un avantage prolifératif aux cellules lymphoïdes dans un contexte de déficit immunitaire est majeur dans les lésions précoces et polymorphes. Ce mécanisme physiopathogénique justifie la surveillance de la charge virale du sang périphérique et de la réponse immune anti-EBV chez les patients transplantés. Les anomalies génétiques plus fréquentes dans les proliférations lymphomateuses monomorphes et tardives correspondent soit à des pertes d’hétérozygotie, soit à des déséquilibres chromosomiques, soit à des mutations aberrantes, soit à des phénomènes d’instabilité des microsatellites aboutissant à des mutations affectant des gènes impliqués dans des phénomènes d’apoptose ou de recombinaison de l’ADN. La connaissance des mécanismes de lymphomagenèse chez ces patients immunodéficients permet une approche de dépistage par le suivi de marqueurs viraux et immunologiques et une attitude thérapeutique ciblée

Lung Fibroblasts from Idiopathic Pulmonary Fibrosis Patients Harbor Short and Unstable Telomeres Leading to Chromosomal Instability

Idiopathic pulmonary fibrosis (IPF) is associated with several hallmarks of aging including telomere shortening, which can result from germline mutations in telomere related genes (TRGs). Here, we assessed the length and stability of telomeres as well as the integrity of chromosomes in primary lung fibroblasts from 13 IPF patients (including seven patients with pathogenic variants in TRGs) and seven controls. Automatized high-throughput detection of telomeric FISH signals highlighted lower signal intensity in lung fibroblasts from IPF patients, suggesting a telomere length defect in these cells. The increased detection of telomere loss and terminal deletion in IPF cells, particularly in TRG-mutated cells (IPF-TRG), supports the notion that these cells have unstable telomeres. Furthermore, fibroblasts from IPF patients with TRGs mutations exhibited dicentric chromosomes and anaphase bridges. Collectively, our study indicates that fibroblasts from IPF patients exhibit telomere and chromosome instability that likely contribute to the physiopathology