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Plasmacytoid dendritic cells (pDCs) are the principal natural type I interferon-producing dendritic cells. Neoplastic expansion of pDCs and pDC precursors leads to blastic plasmacytoid dendritic cell neoplasm (BPDCN), and clonal expansion of mature pDCs has been described in chronic myelomonocytic leukemia. The role of pDC expansion in acute myeloid leukemia (AML) is poorly studied. Here, we characterize patients with AML with pDC expansion (pDC-AML), which we observe in ∼5% of AML cases. pDC-AMLs often possess cross-lineage antigen expression and have adverse risk stratification with poor outcome. RUNX1 mutations are the most common somatic alterations in pDC-AML (>70%) and are much more common than in AML without pDC expansion and BPDCN. We demonstrate that pDCs are clonally related to, as well as originate from, leukemic blasts in pDC-AML. We further demonstrate that leukemic blasts from RUNX1-mutated AML upregulate a pDC transcriptional program, poising the cells toward pDC differentiation and expansion. Finally, tagraxofusp, a targeted therapy directed to CD123, reduces leukemic burden and eliminates pDCs in a patient-derived xenograft model. In conclusion, pDC-AML is characterized by a high frequency of RUNX1 mutations and increased expression of a pDC transcriptional program. CD123 targeting represents a potential treatment approach for pDC-AML., (© 2021 by The American Society of Hematology.)

Histone proteins often come in different variants serving specialized functions in addition to their fundamental role in packaging DNA. The metazoan histone H3.3 has been most closely associated with active transcription. Its role in histone replacement at active genes and promoters is conserved to the single histone H3 in yeast. However, recent genetic studies in flies have challenged its importance as a mark of active chromatin, and revealed unexpected insights into essential functions of H3.3 in the germline. With strikingly little amino acid sequence difference to the canonical H3, H3.3 therefore accomplishes a surprising variety of cellular and developmental processes., (2010 Elsevier Ltd. All rights reserved.)

Antithrombic therapy is recommended to prevent ischemic complications in patients with high-risk non-ST-segment elevation acute coronary syndromes, including patients with unstable angina/non-ST-segment elevation myocardial infarction and patients with ST-segment elevation myocardial infarction undergoing fibrinolysis with fibrin-specific agents. Ischemic benefit from these agents must be balanced against an increased risk of bleeding, which may itself carry adverse long-term consequences. Recent trials suggest that the low-molecular-weight heparin enoxaparin may be superior to unfractionated heparin for preventing ischemic complications, although it also may be associated with an increase in bleeding risk. In two other contemporary trials, the Factor Xa inhibitor fondaparinux improved mortality and morbidity in patients with unstable angina/non-ST-segment elevation myocardial infarction and in patients with ST-segment elevation myocardial infarction undergoing fibrinolytic reperfusion, without increasing bleeding risk. These data underscore the promise of new antithrombotic agents to improve outcomes in acute coronary syndrome (ACS) patients being medically managed.

Sympathetic and parasympathetic reinnervation of the transplanted heart were evaluated by assessing time and frequency domain measurements of heart rate variability at 5 and 8 years. Continuous 24-hour ECG measurements were performed in 13 patients (57 +/- 6 months and 90 +/- 7 months) after orthotopic cardiac transplantation and in 22 healthy age and gender-matched controls, and were analyzed for heart rate variability in the time and frequency domains. Heart rate variability measures reflective of sympathetic reinnervation were sub-normal at 5 years and unchanged at 8 years: those reflective of parasympathetic reinnervation were absent.

Study Objectives: The goal of this study was to determine whether prolonged hospital stay associated with atrial fibrillation or flutter (AF) after coronary artery bypass graft (CABG) surgery is attributable to the characteristics of patients who develop this arrhythmia or to the rhythm disturbance itself., Design: An investigation was conducted through a prospective case series., Setting: Patients were from a single urban teaching hospital., Participants: Consecutive patients undergoing isolated CABG surgery between December 1994 and May 1996 were included in the study., Interventions: No interventions were involved., Results: Of 436 patients undergoing isolated CABG surgery, 101 (23%) developed AF. AF patients were older and more likely to have obstructive lung disease than patients without AF, but both patients with and without AF had similar left ventricular function and extent of coronary disease. ICU and hospital stays were longer in patients with AF. Multivariate analysis, adjusted for age, gender, and race, demonstrated that postoperative hospital stay was 9.2+/-5.3 days in patients with AF and 6.4+/-5.3 days in patients without AF (p<0.001)., Conclusions: Although AF is strongly associated with advanced age, most of the prolonged hospital stay appears to be attributable to the rhythm itself and not to patient characteristics.

Excessive weight gain resulting in obesity is commonly seen after orthotopic heart transplantation. Obesity increases the risk for the development of many significant health problems and the associated morbidity and mortality. The purpose of this study was to define the occurrence, magnitude, and predictors of overweight/obesity in this group. We followed 47 consecutive patients for 1 year after orthotopic heart transplantation for changes in weight. Weight gain from baseline was significant at months 2, 4, 6, 8, and 10, with significant weight increments between each measurement interval (p < 0.05). The mean weight gain was 10.1 kg +/- 1.6 (standard error [SE]) at 12 months. Based on entry body mass index patients were divided into two groups: group I, overweight/obese, body mass index more than 27 kg/m2 (n = 11); group II, not overweight/obese, body mass index 27 kg/m2 or less (n = 36). No significant difference was found in the amount of weight gained between the two groups (group I, 10.3 kg +/- 1.2 [SE]; group II, 10.1 kg +/- 1.4 [SE]). Only age predicted weight gain, with younger patients gaining more than older patients after transplantation (14.2 +/- 13.2 kg versus 8.8 +/- 7.9 kg; p < 0.05). We found no relationship between the observed weight gain and any of the other measured predictors, that is, history of overweight, age, diabetes, family history of overweight, sex, patient's participation in cardiac rehabilitation. The universal nature of this weight gain and the lack of markers predicting patients at greatest risk for obesity underscores the seriousness of this problem.

Comparisons with direct recordings show that the Physiometrics automatic blood-pressure recorder does not accurately reflect intra-arterial pressure and tends to over-read both systolic and diastolic pressures.

Continuous recording of intra-arterial blood pressure in 11 ambulant patients taking postganglionic blocking drugs for the treatment of hypertension has shown an alternating pattern of high pressures at rest and very low pressures associated with exertion during normal daily activities. In 4 patients there was evidence of decreased cerebral or myocardial blood-flow during hypotensive episodes. It is suggested that these agents may predispose towards cerebral and myocardial infarction.