Disease Characteristics and Outcomes of 493 Young Myeloma Patients Treated With Modern Therapies: A Canadian Myeloma Research Group Database Study.

Background: Young patients ≤ 50 years old with multiple myeloma (MM) account for about 10% of cases and are underrepresented in the literature.

Methods: We explored disease characteristics, treatments, and outcomes following modern therapies of young MM patients using the Canadian Myeloma Research Group (CMRG) database. We included 493 patients ≤ 50 years old diagnosed with MM or plasma cell leukemia without concurrent amyloidosis or POEMS syndrome from January 1, 2010, to July 1, 2022.

Multifocal Vitelliform Paravascular Retinopathy (MVPR): A New Disorder in the Vitelliform Spectrum.

Purpose: To describe a new retinal phenotype characterized by bilateral, multifocal, subretinal vitelliform lesions along the vascular arcades that we refer to as multifocal vitelliform paravascular retinopathy (MVPR).

Design: Observational case series.

Methods: Multimodal retinal imaging including color fundus photography, fundus autofluorescence and cross sectional and en-face optical coherence tomography was performed to evaluate and characterize the lesions of MVPR.

Effect of Terminal Phosphate Groups on Collisional Dissociation of RNA Oligonucleotide Anions.

The increasing need for mass spectrometric analysis of RNA molecules calls for a better understanding of their gas-phase fragmentation behaviors. In this study, we investigate the effect of terminal phosphate groups on the fragmentation spectra of RNA oligonucleotides (oligos) using high-resolution mass spectrometry (MS). Negative-ion mode collision-induced dissociation (CID) and higher-energy collisional dissociation (HCD) were carried out on RNA oligos containing a terminal phosphate group on either end, both ends, or neither end.

Motive and opportunity: MYC rearrangements in high-grade B-cell lymphoma with MYC and BCL2 rearrangements (an LLMPP study).

Rearrangements that place the oncogenes MYC, BCL2, or BCL6 adjacent to superenhancers are common in mature B-cell lymphomas. Lymphomas with diffuse large B-cell lymphoma (DLBCL) or high-grade morphology with both MYC and BCL2 rearrangements are classified as high-grade B-cell lymphoma with MYC and BCL2 rearrangements ("double hit"; HGBCL-DH-BCL2) and are associated with aggressive disease and poor outcomes. Although it is established that MYC rearrangements involving immunoglobulin (IG) loci are associated with inferior outcomes relative to those involving other non-IG superenhancers, the frequency of and mechanisms driving IG vs non-IG MYC rearrangements have not been elucidated.

Efficacy and Safety of Tirofiban Before Stenting for Symptomatic Intracranial Atherosclerotic Stenosis: A Randomized Clinical Trial.

Background And Objectives: Acute stent thrombosis (AST) is not uncommon and even catastrophic during intracranial stenting angioplasty in patients with symptomatic high-grade intracranial atherosclerotic stenosis (ICAS). The purpose of this study was to investigate whether adjuvant intravenous tirofiban before stenting could reduce the risk of AST and periprocedural ischemic stroke in patients receiving stent angioplasty for symptomatic ICAS.

Methods: A prospective, multicenter, open-label, randomized clinical trial was conducted from September 9, 2020, to February 18, 2022, at 10 medical centers in China.

The effect of vaginal cylinder inhomogeneity on the HDR brachytherapy dose calculations using Monte Carlo simulations.

Purpose: To analytically assess the heterogeneity effect of vaginal cylinders (VC) made of high-density plastics on dose calculations, considering the prescription point (surface or 5 mm beyond the surface), and benchmark the accuracy of a commercial model-based dose calculation (MBDC) algorithm using Monte Carlo (MC) simulations.

Methods And Materials: The GEANT4 MC code was used to simulate a commercial Ir HDR source and VC, with diameters ranging from 20 to 35 mm, inside a virtual water phantom. Standard plans were generated from a commercial treatment planning system [TPS-BrachyVision ACUROS (BV)] optimized for a treatment length of 5 cm through two dose calculation approaches: (1) assuming all the environment as water (i.

Real-world results of autologous stem cell transplantation in newly diagnosed multiple myeloma: a report from the Canadian Myeloma Research Group database.

Autologous stem cell transplant (ASCT) remains an important option for eligible multiple myeloma (MM) patients as part of initial therapy. Using the Canadian Myeloma Research Group (CMRG) national database, we examined the details and outcomes of ASCT performed as first-line therapy in eligible Canadian MM patients between 2007 to 2021. We included 3821 patients with 72% receiving CyBorD induction and 2061 patients receiving maintenance, consisting of lenalidomide +/- steroids in 78.

Extracellular Matrix Stiffness Regulates Microvascular Stability by Controlling Endothelial Paracrine Signaling to Determine Pericyte Fate.

Background: The differentiation of pericytes into myofibroblasts causes microvascular degeneration, ECM (extracellular matrix) accumulation, and tissue stiffening, characteristics of fibrotic diseases. It is unclear how pericyte-myofibroblast differentiation is regulated in the microvascular environment. Our previous study established a novel 2-dimensional platform for coculturing microvascular endothelial cells (ECs) and pericytes derived from the same tissue.

Indoleamine 2,3-Dioxygenase 1 Deletion-Mediated Kynurenine Insufficiency Inhibits Pathological Cardiac Hypertrophy.

Background: Aberrant amino acid metabolism is implicated in cardiac hypertrophy, while the involvement of tryptophan metabolism in pathological cardiac hypertrophy remains elusive. Herein, we aimed to investigate the effect and potential mechanism of IDO1 (indoleamine 2,3-dioxygenase) and its metabolite kynurenine (Kyn) on pathological cardiac hypertrophy.

Methods: Transverse aortic constriction was performed to induce cardiac hypertrophy in IDO1-knockout (KO) mice and AAV9-cTNT-shIDO1 mice.

A nanobody recognizes a unique conserved epitope and potently neutralizes SARS-CoV-2 omicron variants.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) Omicron variant sub-lineages spread rapidly worldwide, mostly due to their immune-evasive properties. This has put a significant part of the population at risk for severe disease and underscores the need for effective anti-SARS-CoV-2 agents against emergent strains in vulnerable patients. Camelid nanobodies are attractive therapeutic candidates due to their high stability, ease of large-scale production, and potential for delivery via inhalation.

Expanded indication for EUS-guided radiofrequency ablation: management of adrenal tumors.

Background And Aims: EUS-guided radiofrequency ablation (EUS-RFA) has been performed as an alternative to surgery for the treatment of pancreatic tumors. The promising results obtained using this procedure suggest that the indication for EUS-RFA could be expanded to the management of extrapancreatic tumors. Here, we evaluate the feasibility, efficacy, and safety of EUS-RFA in the treatment of left adrenal tumors.

Tirofiban for Stroke without Large or Medium-Sized Vessel Occlusion.

Background: The effects of the glycoprotein IIb/IIIa receptor inhibitor tirofiban in patients with acute ischemic stroke but who have no evidence of complete occlusion of large or medium-sized vessels have not been extensively studied.

Methods: In a multicenter trial in China, we enrolled patients with ischemic stroke without occlusion of large or medium-sized vessels and with a National Institutes of Health Stroke Scale score of 5 or more and at least one moderately to severely weak limb. Eligible patients had any of four clinical presentations: ineligible for thrombolysis or thrombectomy and within 24 hours after the patient was last known to be well; progression of stroke symptoms 24 to 96 hours after onset; early neurologic deterioration after thrombolysis; or thrombolysis with no improvement at 4 to 24 hours.

Identification of carotenoids from fruits and vegetables with or without saponification and evaluation of their antioxidant activities.

This study investigates the composition and form of carotenoids in typical fruits and vegetables obtained through saponification or non-saponification and evaluates the correlation between carotenoids and antioxidant capacity. The results showed that the content of the total carotenoids in non-saponified broccoli was the highest, reaching 1505.93 ± 71.

FHL5 Controls Vascular Disease-Associated Gene Programs in Smooth Muscle Cells.

Background: Genome-wide association studies have identified hundreds of loci associated with common vascular diseases, such as coronary artery disease, myocardial infarction, and hypertension. However, the lack of mechanistic insights for many GWAS loci limits their translation into the clinic. Among these loci with unknown functions is -four-and-a-half LIM (LIN-11, Isl-1, MEC-3) domain 5 (; chr6q16.

Alternating-Current Microgrid Testbed Built with Low-Cost Modular Hardware.

With the growing popularity of microgrids for alternative energy management, there is demand for tools that allow us to study the effect of microgrids in distributed power systems. Popular methods involve software simulation and prototype validation with physical hardware. Simulations often do not capture the complex interactions, and combinations of software simulations with hardware testbeds promise to give a more accurate picture.

Thirty-day and one-year outcomes following transcatheter mitral valve edge-to-edge repair versus transapical mitral valve replacement in patients with left ventricular dysfunction.

Background: A comparison of 30-day and 1-year clinical outcomes in patients with pre-existing left ventricular (LV) dysfunction undergoing transcatheter mitral valve edge-to-edge repair (TEER) or transcatheter transapical mitral valve replacement (TMVR) has not previously been reported.

Aims: We aimed to compare 30-day and 1-year rates of all-cause and cardiovascular mortality as well as rehospitalisation for heart failure (HFH).

Methods: All patients with severe (≥3+) symptomatic mitral regurgitation (MR) and an LV ejection fraction ≤50% who underwent TEER or TMVR over a 5-year period were evaluated.

Deacetylation of Septin4 by SIRT2 (Silent Mating Type Information Regulation 2 Homolog-2) Mitigates Damaging of Hypertensive Nephropathy.

Background: Hypertension can lead to podocyte damage and subsequent apoptosis, eventually resulting in glomerulosclerosis. Although alleviating podocyte apoptosis has clinical significance for the treatment of hypertensive nephropathy, an effective therapeutic target has not yet been identified. The function of septin4, a proapoptotic protein and an important marker of organ damage, is regulated by post-translational modification.