Translating Molecules into Imaging-The Development of New PET Tracers for Patients with Melanoma.

Melanoma is a deadly disease that often exhibits relentless progression and can have both early and late metastases. Recent advances in immunotherapy and targeted therapy have dramatically increased patient survival for patients with melanoma. Similar advances in molecular targeted PET imaging can identify molecular pathways that promote disease progression and therefore offer physiological information.

Relapse of Hepatitis C Virus Cryoglobulinemic Vasculitis After Sustained Viral Response After Interferon-Free Direct-Acting Antivirals.

Introduction: Direct-acting antiviral agents (DAAs) have modified the management of chronic hepatitis C virus (HCV) infection, including HCV-related cryoglobulinemic vasculitis (CryoVas). However, patients might experience vasculitis relapse, and no reliable predictors of CryoVas relapse after sustained virologic response (SVR) have been established. We aimed to describe HCV-CryoVas relapse rates and factors associated with it.

Clinico-biological features of T-cell acute lymphoblastic leukemia with fusion proteins.

T-cell acute lymphoblastic leukemias (T-ALL) represent 15% of pediatric and 25% of adult ALL. Since they have a particularly poor outcome in relapsed/refractory cases, identifying prognosis factors at diagnosis is crucial to adapting treatment for high-risk patients. Unlike acute myeloid leukemia and BCP ALL, chromosomal rearrangements leading to chimeric fusion-proteins with strong prognosis impact are sparsely reported in T-ALL.

COVID-19 skin lesions are rarely positive at RT-PCR test: the macrophage activation with vascular impact and SARS-CoV-2-induced cytokine storm.

Background: Several skin manifestations have been reported since the start of the COVID-19 pandemic: chilblains-like, livedoid lesions, urticaria-like, pseudo-Kawasaki disease, and others. Histopathologic images of these lesions most often show aspects of endothelitis, images similar to autoimmune vasculitis. Cutaneous lesions are often negative at RT-PCR for SARS-CoV-2 virus.

Atrial flutter mimicking ST-elevation myocardial infarction.

A 12 lead electrocardiogram provides an important diagnostic tool for atrial flutter recognition. However, rarely, atrial flutter waves can cause diagnostic challenges by producing ST segment abnormalities mimicking ST segment elevation and result in unnecessary workup and treatment. ​.

PRC2 loss of function confers a targetable vulnerability to BET proteins in T-ALL.

T-cell acute lymphoblastic leukemia (T-ALL) is a group of aggressive hematological cancers with dismal outcomes that are in need of new therapeutic options. Polycomb repressor complex 2 (PRC2) loss-of-function alterations were reported in pediatric T-ALL, yet their clinical relevance and functional consequences remain elusive. Here, we extensively analyzed PRC2 alterations in a large series of 218 adult T-ALL patients.

Epigenetic analysis of patients with T-ALL identifies poor outcomes and a hypomethylating agent-responsive subgroup.

Adult "T cell" acute lymphoblastic leukemia (T-ALL) is an aggressive hematological malignancy that is associated with poor outcomes, requiring additional therapeutic options. The DNA methylation landscapes of adult T-ALL remain undercharacterized. Here, we systematically analyzed the DNA methylation profiles of normal thymic-sorted T cell subpopulations and 143 primary adult T-ALLs as part of the French GRAALL 2003-2005 trial.

Avadomide induces degradation of ZMYM2 fusion oncoproteins in hematologic malignancies.

Thalidomide analogs exert their therapeutic effects by binding to the CRL4 E3 ubiquitin ligase, promoting ubiquitination and subsequent proteasomal degradation of specific protein substrates. Drug-induced degradation of IKZF1 and IKZF3 in B-cell malignancies demonstrates the clinical utility of targeting disease-relevant transcription factors for degradation. Here, we found that avadomide (CC-122) induces CRBN-dependent ubiquitination and proteasomal degradation of ZMYM2 (ZNF198), a transcription factor involved in balanced chromosomal rearrangements with and in aggressive forms of hematologic malignancies.

Oncogenetic landscape and clinical impact of IDH1 and IDH2 mutations in T-ALL.

IDH1 and IDH2 mutations (IDH1/2) are recognized as recurrent genetic alterations in acute myeloid leukemia (AML) and associated with both clinical impact and therapeutic opportunity due to the recent development of specific IDH1/2 inhibitors. In T-cell acute lymphoblastic leukemia (T-ALL), their incidence and prognostic implications remain poorly reported. Our targeted next-generation sequencing approach allowed comprehensive assessment of genotype across the entire IDH1 and IDH2 locus in 1085 consecutive unselected and newly diagnosed patients with T-ALL and identified 4% of, virtually exclusive (47 of 49 patients), IDH1/2.

Long-term follow-up of blinatumomab in patients with relapsed/refractory Philadelphia chromosome-positive B-cell precursor acute lymphoblastic leukaemia: Final analysis of ALCANTARA study.

Aim: To evaluate long-term durability of blinatumomab, a BiTE® (bispecific T-cell engager) molecule, in adults with relapsed/refractory (R/R) Philadelphia chromosome-positive (Ph+) B-cell precursor acute lymphoblastic leukaemia (ALL).

Methods: In this final analysis of an open-label, single-arm, phase 2, multicentre ALCANTARA study (NCT02000427), adults (age ≥18 years) with Ph+ ALL who had relapsed or were refractory to at least one TKI were included. The primary endpoint was the proportion of patients who achieved complete remission (CR)/CR with partial haematologic recovery (CRh) during the first two cycles of blinatumomab treatment.

Who fails to return within 30 days after being tested positive for HIV/STI in a free testing centre?

Background: Some patients who test positive for sexually transmitted infections (STIs) fail to return for results and treatment. To target improvement actions, we need to find out who these patients are. This study aimed to explore factors associated with failure to return within 30 days (FTR30) after testing among patients with positive results in a free STI testing centre in Paris.

Maintenance treatment with fluoropyrimidine plus bevacizumab versus fluoropyrimidine alone after induction chemotherapy for metastatic colorectal cancer: The BEVAMAINT - PRODIGE 71 - (FFCD 1710) phase III study.

Background: Maintenance treatments with fluoropyrimidine alone or combined with bevacizumab after induction chemotherapy are two standard options in first-line metastatic colorectal cancer (mCRC). However, no trial has compared these two maintenance regimens.

Methods: BEVAMAINT is a multicenter, open-label, randomized phase III trial comparing fluoropyrimidine alone or plus bevacizumab as maintenance treatment after induction polychemotherapy in mCRC.

Second-look surgery plus hyperthermic intraperitoneal chemotherapy versus surveillance in patients at high risk of developing colorectal peritoneal metastases (PROPHYLOCHIP-PRODIGE 15): a randomised, phase 3 study.

Background: Diagnosis and treatment of colorectal peritoneal metastases at an early stage, before the onset of signs, could improve patient survival. We aimed to compare the survival benefit of systematic second-look surgery plus hyperthermic intraperitoneal chemotherapy (HIPEC), with surveillance, in patients at high risk of developing colorectal peritoneal metastases.

Methods: We did an open-label, randomised, phase 3 study in 23 hospitals in France.

Blueprint of human thymopoiesis reveals molecular mechanisms of stage-specific TCR enhancer activation.

Cell differentiation is accompanied by epigenetic changes leading to precise lineage definition and cell identity. Here we present a comprehensive resource of epigenomic data of human T cell precursors along with an integrative analysis of other hematopoietic populations. Although T cell commitment is accompanied by large scale epigenetic changes, we observed that the majority of distal regulatory elements are constitutively unmethylated throughout T cell differentiation, irrespective of their activation status.

A transcriptomic continuum of differentiation arrest identifies myeloid interface acute leukemias with poor prognosis.

Classification of acute lymphoblastic and myeloid leukemias (ALL and AML) remains heavily based on phenotypic resemblance to normal hematopoietic precursors. This framework can provide diagnostic challenges for immunophenotypically heterogeneous immature leukemias, and ignores recent advances in understanding of developmental multipotency of diverse normal hematopoietic progenitor populations that are identified by transcriptional signatures. We performed transcriptional analyses of a large series of acute myeloid and lymphoid leukemias and detected significant overlap in gene expression between cases in different diagnostic categories.

Late molecular recurrences in patients with chronic myeloid leukemia experiencing treatment-free remission.

Treatment-free remission (TFR) is an opportunity for patients with chronic myeloid leukemia (CML). Reported cumulative incidence curves of molecular recurrence (MRec) arbor a 2-phase shape with mainly early events, but also some late events (late MRec [LMRec]). Having discontinued our first patient in 2004, we have access to a prolonged follow-up, enabling us to characterize these late events.

Attention Deficit/Hyperactivity Disorder and Global Severity Profiles in Treatment-Seeking Patients with Substance Use Disorders.

Introduction: Comorbid attention deficit/hyperactivity disorder (ADHD) is present in 15-25% of all patients seeking treatment for substance use disorders (SUDs). Some studies suggest that comorbid ADHD increases clinical severity related to SUDs, other psychiatric comorbidities, and social impairment, but could not disentangle their respective influences.

Objectives: To investigate whether comorbid adult ADHD in treatment-seeking SUD patients is associated with more severe clinical profiles in these domains assessed altogether.

Correction: Standardisation and consensus guidelines for minimal residual disease assessment in Philadelphia-positive acute lymphoblastic leukemia (Ph+ALL) by real-time quantitative reverse transcriptase PCR of e1a2 BCR-ABL1.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.