Transcatheter aortic valve replacement in patients with bicuspid aortic valves.

Transcatheter aortic valve replacement (TAVR) for the treatment of severe symptomatic aortic stenosis (AS) has rapidly become the standard of care for expanding clinical indications based on the results of multiple large-scale randomized trials. Patients with bicuspid aortic valve (BAV) have been largely excluded from these trials for a variety of reasons. However, case series and registry data has shown TAVR in BAV to be a safe and efficacious alternative to surgical aortic valve replacement (SAVR) with the possible caveats of increased paravalvular regurgitation (PVR) and need for permanent pacemaker (PPM) implantation.

Publisher Correction: Suppression of insulin feedback enhances the efficacy of PI3K inhibitors.

In this Letter, author Xing Du was incorrectly listed as Du Xing; this has been corrected online.

Prostate cancer: unmet clinical needs and RAD9 as a candidate biomarker for patient management.

Prostate cancer is a complex disease, with multiple subtypes and clinical presentations. Much progress has been made in recent years to understand the underlying genetic basis that drives prostate cancer. Such mechanistic information is useful for development of novel therapeutic targets, to identify biomarkers for early detection or to distinguish between aggressive and indolent disease, and to predict treatment outcome.

Suppression of insulin feedback enhances the efficacy of PI3K inhibitors.

Mutations in PIK3CA, which encodes the p110α subunit of the insulin-activated phosphatidylinositol-3 kinase (PI3K), and loss of function mutations in PTEN, which encodes a phosphatase that degrades the phosphoinositide lipids generated by PI3K, are among the most frequent events in human cancers. However, pharmacological inhibition of PI3K has resulted in variable clinical responses, raising the possibility of an inherent mechanism of resistance to treatment. As p110α mediates virtually all cellular responses to insulin, targeted inhibition of this enzyme disrupts glucose metabolism in multiple tissues.

Transfusion Medicine in a Multidisciplinary Approach to Morbidly Adherent Placenta: Preparing for and Preventing the Worst.

The increasing incidence of placenta accreta has paralleled the rise in its greatest risk factor: cesarean delivery. In placenta accreta, the abnormal invasion of the chorionic villi into the myometrium prevents separation of the placenta at delivery, and the myometrium is unable to contract to prevent hemorrhage. Spontaneous uterine rupture and hemoperitoneum may also occur in the setting of placenta percreta.

Author Correction: Disruption of the beclin 1-BCL2 autophagy regulatory complex promotes longevity in mice.

In this Letter, the graphs in Fig. 2a and c were inadvertently the same owing to a copy and paste error from the original graphs in Prism. The Source Data files containing the raw data were correct.

Disruption of the beclin 1-BCL2 autophagy regulatory complex promotes longevity in mice.

Autophagy increases the lifespan of model organisms; however, its role in promoting mammalian longevity is less well-established. Here we report lifespan and healthspan extension in a mouse model with increased basal autophagy. To determine the effects of constitutively increased autophagy on mammalian health, we generated targeted mutant mice with a Phe121Ala mutation in beclin 1 (Becn1) that decreases its interaction with the negative regulator BCL2.

Clinical Significance of PTEN Deletion, Mutation, and Loss of PTEN Expression in De Novo Diffuse Large B-Cell Lymphoma.

PTEN loss has been associated with poorer prognosis in many solid tumors. However, such investigation in lymphomas is limited. In this study, PTEN cytoplasmic and nuclear expression, PTEN gene deletion, and PTEN mutations were evaluated in two independent cohorts of diffuse large B-cell lymphoma (DLBCL).

Deep Learning for Prediction of Obstructive Disease From Fast Myocardial Perfusion SPECT: A Multicenter Study.

Objectives: The study evaluated the automatic prediction of obstructive disease from myocardial perfusion imaging (MPI) by deep learning as compared with total perfusion deficit (TPD).

Background: Deep convolutional neural networks trained with a large multicenter population may provide improved prediction of per-patient and per-vessel coronary artery disease from single-photon emission computed tomography MPI.

Methods: A total of 1,638 patients (67% men) without known coronary artery disease, undergoing stress Tc-sestamibi or tetrofosmin MPI with new generation solid-state scanners in 9 different sites, with invasive coronary angiography performed within 6 months of MPI, were studied.

Peptidomimetic blockade of MYB in acute myeloid leukemia.

Aberrant gene expression is a hallmark of acute leukemias. MYB-driven transcriptional coactivation with CREB-binding protein (CBP)/P300 is required for acute lymphoblastic and myeloid leukemias, including refractory MLL-rearranged leukemias. Using structure-guided molecular design, we developed a peptidomimetic inhibitor MYBMIM that interferes with the assembly of the molecular MYB:CBP/P300 complex and rapidly accumulates in the nuclei of AML cells.

Clinicopathologic Features and Prognostic Impact of Lymph Node Involvement in Patients With Breast Implant-associated Anaplastic Large Cell Lymphoma.

Breast implant-associated anaplastic large cell lymphoma (BI-ALCL) is a rare T-cell lymphoma that arises around breast implants. Most patients manifest with periprosthetic effusion, whereas a subset of patients develops a tumor mass or lymph node involvement (LNI). The aim of this study is to describe the pathologic features of lymph nodes from patients with BI-ALCL and assess the prognostic impact of LNI.

Outcomes of adults and children with primary mediastinal B-cell lymphoma treated with dose-adjusted EPOCH-R.

Treatment with dose-adjusted EPOCH (etoposide, doxorubicin, cyclophosphamide, vincristine, prednisone) chemotherapy and rituximab (DA-EPOCH-R) has become the standard of care for primary mediastinal B-cell lymphoma (PMBCL) at many institutions despite limited data in the multi-centre setting. We report a large, multi-centre retrospective analysis of children and adults with PMBCL treated with DA-EPOCH-R to characterize outcomes and evaluate prognostic factors. We assessed 156 patients with PMBCL treated with DA-EPOCH-R across 24 academic centres, including 38 children and 118 adults.

Hepatitis C virus positive diffuse large B-cell lymphomas have distinct molecular features and lack BCL2 translocations.

Background: The clinical presentation of patients with hepatitis C virus (HCV)-positive diffuse large B-cell lymphoma (DLBCL) is different from their HCV-negative counterparts, but the underlying molecular and pathological characteristics are largely under investigated. The virus has a role in lymphomagenesis, as witnessed by the curative potential of antiviral therapy in HCV-related low-grade B-cell lymphomas.

Methods: We performed a case-control study including 44 HCV-positive cases of de novo DLBCL, comparing them with 132 HCV-negative patients as controls (ratio 3 to 1).

Calibration and error analysis of metal-oxide-semiconductor field-effect transistor dosimeters for computed tomography radiation dosimetry.

Purpose: Metal-oxide-semiconductor field-effect transistors (MOSFETs) serve as a helpful tool for organ radiation dosimetry and their use has grown in computed tomography (CT). While different approaches have been used for MOSFET calibration, those using the commonly available 100 mm pencil ionization chamber have not incorporated measurements performed throughout its length, and moreover, no previous work has rigorously evaluated the multiple sources of error involved in MOSFET calibration. In this paper, we propose a new MOSFET calibration approach to translate MOSFET voltage measurements into absorbed dose from CT, based on serial measurements performed throughout the length of a 100-mm ionization chamber, and perform an analysis of the errors of MOSFET voltage measurements and four sources of error in calibration.

Nuclear cardiology practices and radiation exposure in Africa: results from the IAEA Nuclear Cardiology Protocols Study (INCAPS).

Objective: While nuclear myocardial perfusion imaging (MPI) offers many benefits to patients with known or suspected cardiovascular disease, concerns exist regarding radiation-associated health effects. Little is known regarding MPI practice in Africa. We sought to characterise radiation doses and the use of MPI best practices that could minimise radiation in African nuclear cardiology laboratories, and compare these to practice worldwide.

Safety of coronary CT angiography and functional testing for stable chest pain in the PROMISE trial: A randomized comparison of test complications, incidental findings, and radiation dose.

Background: Coronary computed tomography angiography (CTA) and functional testing strategies for stable chest pain yield similar outcomes; one aspect that may guide test choice is safety.

Methods: We compared test safety (test complications, incidental findings, and effective radiation dose) between CTA and functional testing as-tested in PROMISE (PROspective Multicenter Imaging Study for Evaluation of Chest Pain). In the subgroup whose physicians intended nuclear stress over other functional tests if randomized to the functional arm, we compared radiation dose of CTA versus nuclear stress and identified characteristics associated with dose.

Concordant bone marrow involvement of diffuse large B-cell lymphoma represents a distinct clinical and biological entity in the era of immunotherapy.

In diffuse large B-cell lymphoma (DLBCL), the clinical and biological significance of concordant and discordant bone marrow (BM) involvement have not been well investigated. We evaluated 712 de novo DLBCL patients with front-line rituximab-containing treatment, including 263 patients with positive and 449 with negative BM status. Compared with negative BM disease, concordant BM adversely impacted overall and progression-free survival, independent of the International Prognostic Index (IPI) and cell-of-origin classification.

AKT Hyperactivation and the Potential of AKT-Targeted Therapy in Diffuse Large B-Cell Lymphoma.

AKT signaling is important for proliferation and survival of tumor cells. The clinical significance of AKT activation in diffuse large B-cell lymphoma (DLBCL) is not well analyzed. Here, we assessed expression of phosphorylated AKT (p-AKT) in 522 DLBCL patients.