ABSTRACT
ABSTRACT: Nonmelanoma skin cancers (NMSCs) in ruxolitinib-treated patients with myeloproliferative neoplasms behave aggressively, with adverse features and high recurrence. In our cohort, mortality from metastatic NMSC exceeded that from myelofibrosis. Vigilant skin assessment, counseling on NMSC risks, and prospective ruxolitinib-NMSC studies are crucial.
Subject(s)
Myeloproliferative Disorders , Pyrazoles , Pyrimidines , Skin Neoplasms , Humans , Prospective Studies , Myeloproliferative Disorders/drug therapy , Nitriles , Skin Neoplasms/drug therapySubject(s)
COVID-19/complications , Myeloproliferative Disorders/complications , Adult , Aged , Aged, 80 and over , COVID-19/diagnosis , COVID-19/epidemiology , COVID-19/therapy , Disease Management , Female , Humans , Male , Middle Aged , Myeloproliferative Disorders/therapy , SARS-CoV-2/isolation & purification , Survival Analysis , United Kingdom/epidemiologyABSTRACT
Enteropathy-associated T cell lymphoma (EATL) is a lethal, and the most common, neoplastic complication of celiac disease. Here, we defined the genetic landscape of EATL through whole-exome sequencing of 69 EATL tumors. SETD2 was the most frequently silenced gene in EATL (32% of cases). The JAK-STAT pathway was the most frequently mutated pathway, with frequent mutations in STAT5B as well as JAK1, JAK3, STAT3, and SOCS1 We also identified mutations in KRAS, TP53, and TERT Type I EATL and type II EATL (monomorphic epitheliotropic intestinal T cell lymphoma) had highly overlapping genetic alterations indicating shared mechanisms underlying their pathogenesis. We modeled the effects of SETD2 loss in vivo by developing a T cell-specific knockout mouse. These mice manifested an expansion of γδ T cells, indicating novel roles for SETD2 in T cell development and lymphomagenesis. Our data render the most comprehensive genetic portrait yet of this uncommon but lethal disease and may inform future classification schemes.
Subject(s)
Enteropathy-Associated T-Cell Lymphoma/physiopathology , Histone-Lysine N-Methyltransferase/physiology , Animals , DNA Copy Number Variations/genetics , Enteropathy-Associated T-Cell Lymphoma/classification , Enteropathy-Associated T-Cell Lymphoma/genetics , Female , Gene Expression Profiling , Gene Silencing , Humans , Male , Mice, Knockout , Middle Aged , Mutation/genetics , Sequence Analysis, DNA , T-Lymphocytes/physiologyABSTRACT
A 57-year-old man developed transient global amnesia within an hour of bolus unfractionated heparin administration on day 4 post-mitral valve replacement. Both immunoglobulin G-specific enzyme-linked immunosorbent assay and serotonin release assay were strongly positive for the antibodies that cause heparin-induced thrombocytopenia. The patient's cognitive functions returned to normal following discontinuation of unfractionated heparin and warfarin and commencement of lepirudin infusion.
Subject(s)
Amnesia, Transient Global/diagnosis , Anticoagulants/adverse effects , Heparin/adverse effects , Thrombocytopenia/complications , Warfarin/adverse effects , Amnesia, Transient Global/chemically induced , Anticoagulants/therapeutic use , Heart Valve Prosthesis Implantation , Hirudins , Humans , Male , Middle Aged , Mitral Valve/pathology , Recombinant Proteins/therapeutic use , Thrombocytopenia/chemically induced , Time FactorsABSTRACT
OBJECTIVES: Peripheral exercise blood pressure and resting central blood pressure are considered more relevant to cardiovascular health than resting peripheral blood pressure. Central exercise blood pressure may well be an even more useful measure, but there is no simple non-invasive means of determining it. The aim of the present study was to establish whether the estimation of central blood pressure from peripheral blood pressure using a transfer function derived at rest, would hold after aerobic exercise. METHODS: Thirty healthy young men were studied before and immediately (< 1 min) and 10 min after 15 min bicycle exercise at 65-70% of maximum heart rate. Simultaneous carotid and radial artery waveforms were recorded, and radial-to-carotid generalized transfer functions (GTF) were calculated using Fourier analysis for rest and immediately postexercise. Central systolic blood pressure (SBP) and augmentation index (AIx) were calculated for measured and derived waves. RESULTS: The resting GTF underestimated central SBP and AIx immediately (-5.8 +/- 2.1 mmHg, P = 0.01; -8.3 +/- 2.9%, P = 0.008) and 10 min after (-2.0 +/- 0.7 mmHg, P = 0.008; -7.0 +/- 2.1%, P = 0.003) exercise. No significant bias was found between measured and derived (using resting GTF) carotid values at rest. The use of an exercise-specific GTF resulted in no specific bias immediately or 10 min after exercise, although it overestimated blood pressure and AIx at rest (2.5 +/- 1.0 mmHg, P = 0.02; 11.3 +/- 3.0%, P = 0.001). CONCLUSION: A peripheral-to-central arterial GTF derived at rest significantly underestimates key measures of central arterial pressure immediately after exercise, and pressure estimations may be improved by the use of an exercise-specific GTF.