Immunotherapy as a turning point in the treatment of acute myeloid leukemia

Acute myeloid leukemia (AML) is a malignant disease of hematopoietic precursors at the earliest stage of maturation, resulting in a clonalproliferation of myoblasts replacing normal hematopoiesis. AML represents one of the most common types of leukemia, mostly affecting elderly patients. To date, standard chemotherapy protocols are only effective in patients at low risk of relapse and therapy-related mortality. The average 5-year overall survival (OS) is approximately 28%. Allogeneic hematopoietic stem cell transplantation (HSCT) improves prognosis but is limited by donor availability, a relatively young age of patients, and absence of significant comorbidities. Moreover, it is associated with significant morbidity and mortality. However, increasing understanding of AML immunobiology is leading to the development of innovative therapeutic strategies. Immunotherapy is considered an attractive strategy for controlling and eliminating the disease. It can be a real breakthrough in the treatment of leukemia, especially in patients who are not eligible forintensive chemotherapy. In this review, we focused on the progress of immunotherapy in the field of AML by discussing monoclonal antibodies (mAbs), immune checkpoint inhibitors, chimeric antigen receptor T cells (CAR-T cells), and vaccine therapeutic choices

Diversity of Cardiologic Issues in a Contemporary Cohort of Women With Breast Cancer

Background: Women with breast cancer (BC) represent a special population particularly exposed to cardiovascular disease (CVD) risk. However, cardiologic assessment in BC is mostly limited to detection of left ventricular dysfunction cardiotoxicity (LVD-CTX) due to anticancer treatments. Our aim was to comprehensively investigate CV profile and events in a contemporary BC cohort. Methods and Results: Records of BC patients referred for a Cardio-Oncologic evaluation before starting anticancer treatments, between 2016 and 2019, were retrospectively reviewed (n = 508). Information regarding prevalence and control of CV risk factors, and novel CVD diagnoses were extracted. Occurrence of LVD-CTX, CV events other than LVD-CTX and mortality was assessed. Mean age of study population was 64 ± 13 years; 287 patients were scheduled to receive anthracycline and 165 anti-HER2 therapy. Overall, 53% of BC women had ≥2 CV risk factors, and 67% had at least one of arterial hypertension, dyslipidaemia or diabetes mellitus not adequately controlled. Eighteen (4%) patients were diagnosed a previously unknown CVD. Over a mean follow-up of 2.5 ± 1 years, 3% of BC patients developed LVD-CTX, 2% suffered from other CV events and 11% died. CV risk factors were not associated with LVD-CTX, except for family history of CAD. On the contrary, patients with other CV events exhibited a worse CV profile. Those who died more commonly experienced CV events other than LVD-CTX (p = 0.02). Conclusions: BC women show a suboptimal CV risk profile and are at risk of CV events not limited to LVD-CTX. A baseline Cardio-Oncologic evaluation was instrumental to implement CV prevention and to optimize CV therapies

Automated motion analysis of bony joint structures from dynamic computer tomography images: A multi-atlas approach

Dynamic computer tomography (CT) is an emerging modality to analyze in-vivo joint kinematics at the bone level, but it requires manual bone segmentation and, in some instances, landmark identification. The objective of this study is to present an automated workflow for the assessment of three-dimensional in vivo joint kinematics from dynamic musculoskeletal CT images. The proposed method relies on a multi-atlas, multi-label segmentation and landmark propagation framework to extract bony structures and detect anatomical landmarks on the CT dataset. The segmented structures serve as regions of interest for the subsequent motion estimation across the dynamic sequence. The landmarks are propagated across the dynamic sequence for the construction of bone embedded reference frames from which kinematic parameters are estimated. We applied our workflow on dynamic CT images obtained from 15 healthy subjects on two different joints: thumb base (n = 5) and knee (n = 10). The proposed method resulted in segmentation accuracies of 0.90 ± 0.01 for the thumb dataset and 0.94 ± 0.02 for the knee as measured by the Dice score coefficient. In terms of motion estimation, mean differences in cardan angles between the automated algorithm and manual segmentation, and landmark identification performed by an expert were below 1◦. Intraclass correlation (ICC) between cardan angles from the algorithm and results from expert manual landmarks ranged from 0.72 to 0.99 for all joints across all axes. The proposed automated method resulted in reproducible and reliable measurements, enabling the assessment of joint kinematics using 4DCT in clinical routine

Heavy-flavor production and medium properties in high-energy nuclear collisions --What next?

Open and hidden heavy-flavor physics in high-energy nuclear collisions are entering a new and exciting stage towards reaching a clearer understanding of the new experimental results with the possibility to link them directly to the advancement in lattice Quantum Chromo-Dynamics (QCD). Recent results from experiments and theoretical developments regarding open and hidden heavy-flavor dynamics have been debated at the Lorentz Workshop Tomography of the Quark-Gluon Plasma with Heavy Quarks, which was held in October 2016 in Leiden, The Netherlands. In this contribution, we summarize identified common understandings and developed strategies for the upcoming five years, which aim at achieving a profound knowledge of the dynamical properties of the quark-gluon plasma

QCD and strongly coupled gauge theories : challenges and perspectives

We highlight the progress, current status, and open challenges of QCD-driven physics, in theory and in experiment. We discuss how the strong interaction is intimately connected to a broad sweep of physical problems, in settings ranging from astrophysics and cosmology to strongly coupled, complex systems in particle and condensed-matter physics, as well as to searches for physics beyond the Standard Model. We also discuss how success in describing the strong interaction impacts other fields, and, in turn, how such subjects can impact studies of the strong interaction. In the course of the work we offer a perspective on the many research streams which flow into and out of QCD, as well as a vision for future developments.Peer reviewe

Therapeutic Choice in Older Patients with Acute Myeloid Leukemia: A Matter of Fitness

Acute myeloid leukemia (AML), with an incidence increasing with age, is the most common acute leukemia in adults. Concurrent comorbidities, mild to severe organ dysfunctions, and low performance status (PS) are frequently found in older patients at the onset, conditioning treatment choice and crucially influencing the outcome. Although anthracyclines plus cytarabine-based chemotherapy, also called "7 + 3" regimen, remains the standard of care in young adults, its use in patients older than 65 years should be reserved to selected cases because of higher incidence of toxicity. These adverse features of AML in the elderly underline the importance of a careful patient assessment at diagnosis as a critical tool in the decision-making process of treatment choice. In this review, we will describe selected recently approved drugs as well as examine prognostic algorithms that may be helpful to assign treatment in elderly patients properly

MitraClip XTR Implantation to Treat Torrential Tricuspid Regurgitation After Failed Annulopasty

Transcatheter edge-to-edge tricuspid valve repair is emerging as an alternative therapeutic option in symptomatic patients with severe tricuspid regurgitation deemed unfit for open surgery. However, the presence of a dehiscent ring usually prevents transcatheter tricuspid valve intervention. Herein, we report a case of torrential tricuspid regurgitation secondary to ring dehiscence successfully treated with a MitraClip. (C) 2020 by The Society of Thoracic Surgeon

Anthracycline, taxane, and trastuzumab-based neoadjuvant chemotherapy in HER2-positive early breast cancer: phase II trial

Objective: Neoadjuvant chemotherapy has become the preferred treatment in HER2-positive early breast cancer. Several trials investigated the neoadjuvant efficacy of dual HER2 blockade with anthracycline-free chemotherapy, whereas few data are available on single-agent trastuzumab and anthracycline-based regimens, which represent the standard of care in the adjuvant setting. This phase II, single-arm trial assessed anthracycline-based chemotherapy and trastuzumab as neoadjuvant treatment for high-risk HER2-positive breast cancer. Methods: Forty-three patients with stage II\u2013III HER2-positive breast cancer were treated with 4 courses of neoadjuvant 5-fluorouracil 600 mg/m2, epirubicin 90 mg/m2, cyclophosphamide 600 mg/m2 (FEC 74) every 21 days, followed by 12 courses of weekly paclitaxel 80 mg/m2 and trastuzumab 2 mg/Kg IV (loading dose 4 mg/kg). Results: Pathologic complete response (pCR) was observed in 22 (51%) of 43 patients. After a median follow-up of 6 years, the 5-year disease-free survival and overall survival were 85.8% (95% confidence interval 75.9%\u201397%) and 89.6% (80.4%\u201399.8%), respectively. A temporary decrease in left ventricular ejection fraction was observed in two patients. No cardiac death or congestive heart failure occurred. One patient died due to febrile neutropenia. Conclusions: FEC 74 followed by paclitaxel and trastuzumab was associated with high pCR rates and favorable long-term outcomes. However, this regimen was associated with relevant hematologic toxicity