Nivolumab to restore T-cell fitness in CAR-T refractory multiple myeloma.

Efficacy and durability remain central shortcomings of T-cell based therapies in multiple myeloma (MM). Here, we employ blood-based transcriptional T-cell profiling to define impaired T-cell fitness as putative biomarker associated with sensitivity to PD1 inhibition in CAR-T refractory MM patients.

Breast incidentaloma: Cardiac PET readers beware.

Breast cancer remains one of the most common causes of cancer and cancer-related death in women. With increases in medical imaging utilization, incidentally detected cancer has become more prevalent. Specifically, breast cancer can be incidentally detected on nuclear cardiac imaging scans due to its high metabolic activity and because the tumor may fall within the field of view during these studies.

Development of hyperdiploidy starts at an early age and takes a decade to complete.

Nearly half of multiple myeloma (MM) patients have hyperdiploidy (HMM) at diagnosis. Although HMM occurs early, the mutational processes before and after hyperdiploidy are still unclear. Here, we used 72 WGS samples from patients with HMM and identified pre and post HMM mutation to define the chronology of development of hyperdipoidy.

Serum free light chains in a racially diverse population including African Americans and populations from South Africa.

Detection of light chain (LC) monoclonal gammopathies (MG) traditionally relies on serum free LC (FLC) κ, λ, and their ratio (κ/λ) reference ranges based on a mostly White population. We investigated FLC values in a racially diverse population by screening 10,035 individuals for heavy chain MG, identifying 9,028 negative cases whose FLC were measured. Participants included 4,149 from the PROMISE Study (US, n=2,383; South Africa, n=1,766) and 4,879 from the Mass General Brigham Biobank, with 44% self-identifying as Black.

Lymphopenia predicts poor outcomes in newly diagnosed multiple myeloma.

Bone marrow microenvironment plays an important role in promoting growth and survival of multiple myeloma (MM) cells. The tumor-promoting immune microenvironment is augmented while antitumor immune responses are inhibited. Although clinical and genomic markers of high-risk MM have been described, the immune status is just being recognized as a potential mediator of disease behavior.

EASIX-guided risk stratification for complications and outcome after CAR T-cell therapy with ide-cel in relapsed/refractory multiple myeloma.

Background: Chimeric antigen receptor (CAR) T-cell therapy has demonstrated significant benefits in the treatment of relapsed/refractory multiple myeloma (RRMM). However, these outcomes can be compromised by severe complications, including cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome (ICANS) and immune effector cell-associated hematotoxicity (ICAHT), predisposing for life-threatening infections.

Methods: This retrospective observational study examined a total of 129 patients with RRMM who had received idecabtagene vicleucel (ide-cel) at two major myeloma centers in Germany and one center in the USA to assess the Endothelial Activation and Stress Index (EASIX) as a risk marker for an unfavorable clinical course and outcome after CAR T-cell therapy.

Fracture Resistance of Zirconia Surveyed Crowns With Digitally Designed and Hand-Modified Occlusal Rest Seats.

Background In light of the trend of using zirconia crowns, clinicians will likely face abutment included in removable partial dentures (RPD) designs with existing zirconia. However, the decision to replace the existing crown with a surveyed crown or modify the existing crown to accept the RPD is unclear. To the best of our knowledge, there is a lack of literature on the effect of preparing a rest seat on the existing monolithic zirconia crown in the patient's mouth on the fracture resistance of the crown.

Transcriptional regulation of the postnatal cardiac conduction system heterogeneity.

The cardiac conduction system (CCS) is a network of specialized cardiomyocytes that coordinates electrical impulse generation and propagation for synchronized heart contractions. Although the components of the CCS, including the sinoatrial node, atrioventricular node, His bundle, bundle branches, and Purkinje fibers, were anatomically discovered more than 100 years ago, their molecular constituents and regulatory mechanisms remain incompletely understood. Here, we demonstrate the transcriptomic landscape of the postnatal mouse CCS at a single-cell resolution with spatial information.

Natural Language Processing Algorithm to Extract Multiple Myeloma Stage From Oncology Notes in the Veterans Affairs Healthcare System.

Purpose: Stage in multiple myeloma (MM) is an essential measure of disease risk, but its measurement in large databases is often lacking. We aimed to develop and validate a natural language processing (NLP) algorithm to extract oncologists' documentation of stage in the national Veterans Affairs (VA) Healthcare System.

Methods: Using nationwide electronic health record (EHR) and cancer registry data from the VA Corporate Data Warehouse, we developed and validated a rule-based NLP algorithm to extract oncologist-determined MM stage.

The Effect of Student Experience and Tooth Location on Finish Line Width and Angle of Full Metal Crown Preparations in Preclinical Setting.

Purpose: To determine the effect of experience and tooth location on the finish line width and angle of crown preparations performed by undergraduate students.

Methods: Eighty full metal crown preparations on typodont teeth were divided into four groups: Group 1: 20 preparations performed on mandibular first molar in the first semester. Group 2: 20 preparations performed on mandibular first molar in the second semester.

Neuroparacoccidioidomycosis.

Paracoccidioidomycosis (PCM) is caused by a dimorphic fungus Paracoccidioides Brasiliensis and is endemic to subtropical areas of Central and South America. CNS involvement of PCM is extremely variable. NeuroPCM is found in 9.

Venetoclax resistance leads to broad resistance to standard-of-care anti-MM agents, but not to immunotherapies.

To our knowledge, venetoclax is the first example of personalized medicine for multiple myeloma (MM), with meaningful clinical activity as a monotherapy and in combination in patients with myeloma harboring the t(11:14) translocation. However, despite the high response rates and prolonged progression-free survival, a significant proportion of patients eventually relapse. Here, we aim to study adaptive molecular responses after the acquisition of venetoclax resistance in sensitive t(11:14) MM cell models.

Bone marrow stromal cells induce chromatin remodeling in multiple myeloma cells leading to transcriptional changes.

The natural history of multiple myeloma is characterized by its localization to the bone marrow and its interaction with bone marrow stromal cells. The bone marrow stromal cells provide growth and survival signals, thereby promoting the development of drug resistance. Here, we show that the interaction between bone marrow stromal cells and myeloma cells (using human cell lines) induces chromatin remodeling of cis-regulatory elements and is associated with changes in the expression of genes involved in the cell migration and cytokine signaling.

Isatuximab, carfilzomib, lenalidomide, and dexamethasone in patients with newly diagnosed, transplantation-eligible multiple myeloma (SKylaRk): a single-arm, phase 2 trial.

Background: Isatuximab is a CD38 monoclonal antibody approved for relapsed or refractory multiple myeloma. We aimed to evaluate the addition of isatuximab to weekly carfilzomib (K), lenalidomide (R), and dexamethasone (d; Isa-KRd) in transplant-eligible patients with newly diagnosed multiple myeloma and stratified maintenance by cytogenetic risk.

Methods: This single-arm phase 2 trial was done at three cancer centres (two hospitals and a cancer institute) in Boston (MA, USA).