BCL2 Protein Progressively Declines during Robust CLL Clonal Expansion: Potential Impact on Venetoclax Clinical Efficacy and Insights on Mechanism.

CLL B cells express elevated pro-survival BCL2, and its selective inhibitor, venetoclax, significantly reduces leukemic cell load, leading to clinical remission. Nonetheless, relapses occur. This study evaluates the hypothesis that progressively diminished BCL2 protein in cycling CLL cells within patient lymph node niches contributes to relapse.

Transcranial MRI-guided Histotripsy Targeting Using MR-thermometry and MR-ARFI.

Objective: Transcranial magnetic resonance imaging (MRI)-guided histotripsy has been demonstrated to treat various locations in in vivo swine brain through a human skull. To ensure that the histotripsy treatment is delivered to the intended target location, accurate pre-treatment targeting is necessary. In this work, we investigate the feasibility of MR-thermometry and MR-acoustic radiation force imaging (MR-ARFI) to perform pre-treatment targeting of histotripsy in ex vivo bovine brain through a human skull.

Successful colonization of the testicular germinal epithelium by bone marrow stem cells producing spermatozoa of donor genotype is rare.

Background: It is not known whether bone marrow stem cells when injected intravenously for a bone marrow transplant colonize the human testicular epithelium. No previous studies of sperm genotype after bone marrow transplantation are reported.

Objectives: To differentiate host from donor genotype in spermatozoa of men who have undergone successful bone marrow transplants.

Effectiveness and safety of immune checkpoint inhibitors in Black patients versus White patients in a US national health system: a retrospective cohort study.

Background: Black patients were severely under-represented in the clinical trials that led to the approval of immune checkpoint inhibitors (ICIs) for all cancers. The aim of this study was to characterise the effectiveness and safety of ICIs in Black patients.

Methods: We did a retrospective cohort study of patients in the US Veterans Health Administration (VHA) system's Corporate Data Warehouse containing electronic medical records for all patients who self-identified as non-Hispanic Black or African American (referred to as Black) or non-Hispanic White (referred to as White) and received PD-1, PD-L1, CTLA-4, or LAG-3 inhibitors between Jan 1, 2010, and Dec 31, 2023.

Pan-Cancer Survival Impact of Immune Checkpoint Inhibitors in a National Healthcare System.

Background: The cumulative, health system-wide survival benefit of immune checkpoint inhibitors (ICIs) is unclear, particularly among real-world patients with limited life expectancies and among subgroups poorly represented on clinical trials. We sought to determine the health system-wide survival impact of ICIs.

Methods: We identified all patients receiving PD-1/PD-L1 or CTLA-4 inhibitors from 2010 to 2023 in the national Veterans Health Administration (VHA) system (ICI cohort) and all patients who received non-ICI systemic therapy in the years before ICI approval (historical control).

Less is more: An analysis of venetoclax and hypomethylating agent post-induction treatment modifications in AML.

Venetoclax (Ven) combined with a hypomethylating agent (HMA) enhances survival in elderly/unfit acute myeloid leukemia (AML) patients, yet often necessitates regimen modifications due to intolerance. However, it is unclear how these modifications affect patient outcome. This retrospective cohort study evaluates the impact of post-induction HMA/Ven regimen modifications on disease progression and survival.

Relationships Between Running Biomechanics and Femoral Articular Cartilage Thickness and Composition in Anterior Cruciate Ligament Reconstruction Patients.

Background: Although individuals with anterior cruciate ligament reconstruction (ACLR) are at high risk for posttraumatic osteoarthritis, mechanisms underlying the relationship between running and knee cartilage health remain unclear.

Objective: We aimed to investigate how 30 min of running influences femoral cartilage thickness and composition and their relationships with running biomechanics in patients with ACLR and controls.

Methods: Twenty patients with ACLR (time post-ACLR: 14.

The potential of micro- and nanoplastics to exacerbate the health impacts and global burden of non-communicable diseases.

Non-communicable diseases (NCD) constitute one of the highest burdens of disease globally and are associated with inflammatory responses in target organs. There is increasing evidence of significant human exposure to micro- and nanoplastics (MnPs). This review of environmental MnP exposure and health impacts indicates that MnP particles, directly and indirectly through their leachates, may exacerbate inflammation.

Results for the London investigation into dielectric scanning of lesions study of the MARIA® M6 breast imaging system.

Objectives: Determine the proportion of breast cancers for which MARIA® findings correspond to the cancer, with stratification by breast density and histological type. Investigate performance in symptomatic lesions. Gain patient feedback on experience with MARIA®.

Impact of sequencing of androgen receptor-signaling inhibition and radiotherapy in prostate cancer: importance of homologous recombination disruption.

Purpose: The synergy of combining androgen receptor-signaling inhibition (ARSI) to radiotherapy (RT) in prostate cancer has been largely attributed to non-homologous end joining (NHEJ) inhibition. However, this mechanism is unlikely to explain recently observed trial results that demonstrated the sequencing of ARSI and RT significantly impacts clinical outcomes, with adjuvant ARSI following RT yielding superior outcomes to neoadjuvant/concurrent therapy. We hypothesized this is driven by differential effects on AR-signaling and alternative DNA repair pathway engagement based on ARSI/RT sequencing.

Characterization of the Intraclonal Complexity of Chronic Lymphocytic Leukemia B Cells: Potential Influences of B-Cell Receptor Crosstalk with Other Stimuli.

Chronic lymphocytic leukemia (CLL) clones contain subpopulations differing in time since the last cell division ("age"): recently born, proliferative (PF; CXCR4CD5), intermediate (IF; CXCR4CD5), and resting (RF; CXCR4CD5) fractions. Herein, we used deuterium (H) incorporation into newly synthesized DNA in patients to refine the kinetics of CLL subpopulations by characterizing two additional CXCR4/CD5 fractions, i.e.

Probability of Cavitation in a Custom Iron-Based Coupling Medium for Transcranial Magnetic Resonance-Guided Focused Ultrasound Procedures.

Objective: A coupling bath of circulating, chilled, degassed water is essential to safe and precise acoustic transmittance during transcranial magnetic resonance-guided focused ultrasound (tMRgFUS) procedures, but the circulating water impairs the critical real-time magnetic resonance imaging (MRI). An iron-based coupling medium (IBCM) using iron oxide nanoparticles previously developed by our group increased the relaxivity of the coupling bath such that it appears to be invisible on MRI compared with degassed water. However, the nanoparticles also reduced the pressure threshold for cavitation.

Dark band artifact in transcranial MR-guided focused ultrasound: Mechanism and mitigation with passive crossed wire antennas.

Current FDA-approved transcranial MR-guided focused ultrasound (tcMRgFUS) transducers cause a curved dark band in 3 T brain images that runs through midbrain targets of ablative treatments for essential tremor and other applications, and signal is reduced by at least 25% elsewhere in the brain. This limits the set of scans that can be performed to guide and assess the effects of treatment. An electromagnetic simulation study was performed to elucidate the mechanisms causing the dark band.

Comparison of Methemoglobin, Deoxyhemoglobin, and Ferrous Nitrosyl Hemoglobin as Potential MRI Contrast Agents.

Gadolinium-based contrast agents (GBCAs) are in widespread use to enhance magnetic resonance imaging for evaluating vascular pathology. However, safety concerns and limitations regarding the use of GBCAs has led to an increased interest in alternative contrast agents. Previously, methemoglobin (metHb) and oxygen-free hemoglobin (HHb) have been shown to increase the T1-weighted signal intensity of blood, which is associated with a decrease in the T1 parameter and an enhanced contrast of the image.

Prospective Evaluation of Limited-Stage Small Cell Lung Cancer Radiotherapy Fractionation Regimen Usage and Acute Toxicity in a Large Statewide Quality Collaborative.

Purpose: National guidelines on limited-stage small cell lung cancer (LS-SCLC) treatment give preference to a hyperfractionated regimen of 45 Gy in 30 fractions delivered twice daily; however, use of this regimen is uncommon compared with once-daily regimens. The purpose of this study was to characterize the LS-SCLC fractionation regimens used throughout a statewide collaborative, analyze patient and treatment factors associated with these regimens, and describe real-world acute toxicity profiles of once- and twice-daily radiation therapy (RT) regimens.

Methods And Materials: Demographic, clinical, and treatment data along with physician-assessed toxicity and patient-reported outcomes were prospectively collected by 29 institutions within the Michigan Radiation Oncology Quality Consortium between 2012 and 2021 for patients with LS-SCLC.

Quantitative background parenchymal enhancement and fibro-glandular density at breast MRI: Association with BRCA status.

Objectives: To investigate whether MRI-based measurements of fibro-glandular tissue volume, breast density (MRBD), and background parenchymal enhancement (BPE) could be used to stratify two cohorts of healthy women: BRCA carriers and women at population risk of breast cancer.

Methods: Pre-menopausal women aged 40-50 years old were scanned at 3 T, employing a standard breast protocol including a DCE-MRI (35 and 30 participants in high- and low-risk groups, respectively). The dynamic range of the DCE protocol was characterised and both breasts were masked and segmented with minimal user input to produce measurements of fibro-glandular tissue volume, MRBD, and voxelwise BPE.

Initial Feasibility and Acute Toxicity Outcomes From a Phase 2 Trial of F-Fluorodeoxyglucose Positron Emission Tomography Response-Based De-escalated Definitive Chemoradiotherapy for p16+ Oropharynx Cancer: A Planned Interim Analysis.

Purpose: F-Fluorodeoxyglucose positron emission tomography (FDG-PET) parameters are prognostic of oncologic outcomes in human papillomavirus-associated oropharyngeal squamous cell carcinoma (OPSCC). We used FDG-PET imaging biomarkers to select patients for de-escalated chemoradiotherapy (CRT), hypothesizing that acute toxicity will be improved with de-escalation.

Methods And Materials: This is a planned interim initial feasibility and acute toxicity report from a phase 2, prospective, nonrandomized study, which enrolled patients with stage I-II p16+ OPSCC.

Magnetic Resonance Thermometry Targeting for Magnetic Resonance-Guided Histotripsy Treatments.

Objective: The potential of transcranial magnetic resonance (MR)-guided histotripsy for brain applications has been described in prior in vivo studies in the swine brain through an excised human skull. The safety and accuracy of transcranial MR-guided histotripsy (tcMRgHt) rely on pre-treatment targeting guidance. In the work described here, we investigated the feasibility and accuracy of using ultrasound-induced low-temperature heating and MR thermometry for histotripsy pre-treatment targeting in ex vivo bovine brain.

Cardiac and Pulmonary Dosimetric Parameters in Patients With Lung Cancer Undergoing Postoperative Radiation Therapy Across a Statewide Consortium.

Purpose: The recently published Lung Adjuvant Radiotherapy Trial (Lung ART) reported increased rates of cardiac and pulmonary toxic effects in the postoperative radiation therapy (PORT) arm. It remains unknown whether the dosimetric parameters reported in Lung ART are representative of contemporary real-world practice, which remains relevant for patients undergoing PORT for positive surgical margins. The purpose of this study was to examine heart and lung dose exposure in patients receiving PORT for non-small cell lung cancer across a statewide consortium.

Intersection of immune and oncometabolic pathways drives cancer hyperprogression during immunotherapy.

Immune checkpoint blockade (ICB) can produce durable responses against cancer. We and others have found that a subset of patients experiences paradoxical rapid cancer progression during immunotherapy. It is poorly understood how tumors can accelerate their progression during ICB.