Tailored Digital PCR Follow-Up of Rare Fusion Transcripts after Initial Detection through RNA Sequencing in Hematological Malignancies.

The management of hematologic malignancies has entered a new era in which minimal residual disease (MRD) monitoring plays a pivotal role. Well-established molecular targets, such as PML::RARA, CBFB::MYH11, or RUNX1::RUNX1T1, are conventionally tracked by quantitative RT-PCR. Recently, a broader landscape of fusion transcripts has been unveiled through transcriptomic analysis. These newly discovered fusion transcripts may emerge as novel molecular markers for MRD quantification. In this study, we compared a targeted RNA-sequencing (RNA-seq) approach (FusionPlex) with a whole-transcriptomic strategy (Advanta RNA-Seq XT) for fusion detection in a training set of 21 samples. We evidenced a concordance of 100% for the detection of known fusions, and showed a good correlation for gene expression quantification between the two techniques (Spearman r = 0.77). Additionally, we prospectively evaluated the identification of fusions by targeted RNA-seq in a real-life series of 126 patients with hematological malignancy. At least one fusion transcript was detected for 60 patients (48%). We designed tailored digital PCR assays for 11 rare fusions, and validated this technique for MRD quantification with a limit of detection of <0.01%. The combination of RNA-seq and tailored digital PCR may become a new standard for MRD evaluation in patients lacking conventional molecular targets.

Distinct clinico-molecular arterial and venous thrombosis scores for myeloproliferative neoplasms risk stratification.

Current recommended risk scores to predict thrombotic events associated with myeloproliferative neoplasms (MPN) do not discriminate between arterial and venous thrombosis despite their different physiopathology. To define novel stratification systems, we delineated a comprehensive landscape of MPN associated thrombosis across a large long-term follow-up MPN cohort. Prior arterial thrombosis, age >60 years, cardiovascular risk factors and presence of TET2 or DNMT3A mutations were independently associated with arterial thrombosis in multivariable analysis. ARTS, an ARterial Thrombosis Score, based on these four factors, defined low- (0.37% patients-year) and high-risk (1.19% patients-year) patients. ARTS performance was superior to the two-tiered conventional risk stratification in our training cohort, across all MPN subtypes, as well as in two external validation cohorts. Prior venous thrombosis and presence of a JAK2V617F mutation with a variant allelic frequency ≥50% were independently associated with venous thrombosis. The discrimination potential of VETS, a VEnous Thrombosis Score based on these two factors, was poor, similar to the two-tiered conventional risk stratification. Our study pinpoints arterial and venous thrombosis clinico-molecular differences and proposes an arterial risk score for more accurate patients' stratification. Further improvement of venous risk scores, accounting for additional factors and considering venous thrombosis as a heterogeneous entity is warranted.

Representation of women at American Psychiatric Association annual meetings over 10 years (between 2009 and 2019).

OBJECTIVE: Sex disparity is a major societal issue. The aim of this paper was to describe changes in the representation of women among speakers of the American Psychiatric Association (APA) annual meeting over 10 years, between 2009 and 2019 and to compare them to changes in the proportion of women among American psychiatrists. METHODS: Data were collected from the programs of the APA annual meetings of 2009 and 2019, and from the Association of American Medical Colleges. Descriptive and comparative statistical analyses were performed. RESULTS: There were 1,138 distinct speakers at the 2009 conference and 1,784 at the 2019 conference. The number of distinct female speakers increased from 413 (36.3%) to 813 (45.6%). The proportion of female speakers at the meetings was almost equivalent to the proportion of women in the American psychiatrists' workforce. The number of female chairs increased from 158 (39.6%) to 322 (46.4%). There were 38 female speakers in child and adolescent psychiatry in 2009 (51.4% of 74 speakers) and 74 in 2019 (51.0% of 155 speakers). CONCLUSIONS: The representation of women at the APA annual meetings increased between 2009 and 2019. At the same time, the growth in the percentage of women in the American psychiatrists' workforce was slower. The APA appears to promote female representation during its annual meetings.