Head-to-head comparison of palbociclib and ribociclib in first-line treatment of HR-positive/HER2-negative metastatic breast cancer with real-world data from the OPAL registry.

Cyclin-dependent kinase 4/6 inhibitors (CDKIs) in combination with endocrine therapy (ET) are the standard-of-care in the first-line treatment of HR-positive, HER2-negative metastatic breast cancer. In the absence of direct head-to-head trials comparing the efficacy and safety of the different CDKIs, the individual choice of treatment in everyday practice is complex. Inverse probability of treatment weighting was used to emulate a head-to-head comparison of palbociclib +ET (PALBO) and ribociclib +ET (RIBO) in patients recruited into the prospective, observational, multicenter registry platform OPAL (NCT03417115).

Relevance of Prostatic Fluid on the Apparent Diffusion Coefficient: An Inversion Recovery Diffusion-Weighted Imaging Investigation.

Objectives: Diffusion-weighted imaging (DWI) is pivotal for prostate magnetic resonance imaging. This is rooted in the generally reduced apparent diffusion coefficient (ADC) observed in prostate cancer in comparison to healthy prostate tissue. This difference originates from microstructural tissue composition changes, including a potentially decreased fluid-containing lumen volume.

mapping of the chemical exchange relayed nuclear Overhauser effect using deep magnetic resonance fingerprinting.

Noninvasive magnetic resonance imaging (MRI) of the relayed nuclear Overhauser effect (rNOE) constitutes a promising approach for gaining biological insights into various pathologies, including brain cancer, kidney injury, ischemic stroke, and liver disease. However, rNOE imaging is time-consuming and prone to biases stemming from the water T1 and the semisolid magnetization transfer (MT) contrasts. Here, we developed a rapid rNOE quantification approach, combining magnetic resonance fingerprinting (MRF) acquisition with deep-learning-based reconstruction.

MR-zero meets FLASH - controlling the transient signal decay in gradient- and RF-spoiled gradient echo sequences.

Purpose: The complex signal decay during the transient FLASH MRI readout can lead to artifacts in magnitude and phase images. We show that target-driven optimization of individual RF flip angles and phases can realize near-ideal signal behavior and mitigate artifacts.

Methods: The differentiable end-to-end optimization framework MR-zero is used to optimize RF trains of the FLASH sequence.

Palbociclib in Combination with either Aromatase Inhibitors or Fulvestrant for Patients with Advanced HR+/HER2- Breast Cancer in Germany: Final Results of the Phase 2 Multicohort INGE-B Trial.

Introduction: The INGE-B trial (NCT02894398) aimed to confirm the efficacy and safety data from the PALOMA trials for patients treated first line (1L) with palbociclib (PAL) and letrozole or 1L and later line with PAL and fulvestrant. In addition, so far lacking evidence for efficacy and safety on the combination of PAL with anastrozole, exemestane (1L), or letrozole (later line) was investigated.

Methods: The prospective, multicenter, multicohort phase 2 trial INGE-B enrolled adult patients with locally advanced, inoperable, or metastatic HR+/HER2- breast cancer in Germany.

Motion and magnetic field inhomogeneity correction techniques for chemical exchange saturation transfer (CEST) MRI: A contemporary review.

Chemical exchange saturation transfer (CEST) magnetic resonance imaging (MRI) has emerged as a powerful imaging technique sensitive to tissue molecular composition, pH, and metabolic processes in situ. CEST MRI uniquely probes the physical exchange of protons between water and specific molecules within tissues, providing a window into physiological phenomena that remain invisible to standard MRI. However, given the very low concentration (millimolar range) of CEST compounds, the effects measured are generally only on the order of a few percent of the water signal.

Calibration-free whole-brain CEST imaging at 7T with parallel transmit pulse design for saturation homogeneity utilizing universal pulses (PUSHUP).

Purpose: Chemical exchange saturation transfer (CEST) measurements at ultra-high field (UHF) suffer from strong saturation inhomogeneity. Retrospective correction of this inhomogeneity is possible to some extent, but requires a time-consuming repetition of the measurement. Here, we propose a calibration-free parallel transmit (pTx)-based saturation scheme that homogenizes the saturation over the imaging volume, which we call PUlse design for Saturation Homogeneity utilizing Universal Pulses (PUSHUP).

Caspase-8 promotes scramblase-mediated phosphatidylserine exposure and fusion of osteoclast precursors.

Efficient cellular fusion of mononuclear precursors is the prerequisite for the generation of fully functional multinucleated bone-resorbing osteoclasts. However, the exact molecular factors and mechanisms controlling osteoclast fusion remain incompletely understood. Here we identify RANKL-mediated activation of caspase-8 as early key event during osteoclast fusion.

Enhanced and robust contrast in CEST MRI: Saturation pulse shape design via optimal control.

Purpose: To employ optimal control for the numerical design of Chemical Exchange Saturation Transfer (CEST) saturation pulses to maximize contrast and stability against inhomogeneities.

Theory And Methods: We applied an optimal control framework for the design pulse shapes for CEST saturation pulse trains. The cost functional minimized both the pulse energy and the discrepancy between the corresponding CEST spectrum and the target spectrum based on a continuous radiofrequency (RF) pulse.

Improved quantification in CEST-MRI by joint spatial total generalized variation.

Purpose: In this work, the use of joint Total Generalized Variation (TGV) regularization to improve Multipool-Lorentzian fitting of chemical exchange saturation transfer (CEST) Spectra in terms of stability and parameter signal-to-noise ratio (SNR) was investigated.

Theory And Methods: The joint TGV term was integrated into the nonlinear parameter fitting problem. To increase convergence and weight the gradients, preconditioning using a voxel-wise singular value decomposition was applied to the problem, which was then solved using the iteratively regularized Gauss-Newton method combined with a Primal-Dual splitting algorithm.

Phase distribution graphs for fast, differentiable, and spatially encoded Bloch simulations of arbitrary MRI sequences.

Purpose: An analytical approach to Bloch simulations for MRI sequences is introduced that enables time efficient calculations of signals free of Monte-Carlo noise, while providing full flexibility and differentiability in RF flip angles, RF phases, magnetic field gradients and time, as well as insights into image formation.

Theory And Methods: We present an implementation of the extended phase graph (EPG) concept implemented in PyTorch, including an efficient state selection algorithm. This simulation is compared with an isochromat-based Bloch simulation with random isochromat distribution as well as with in vivo measurements using the Pulseq standard.

Low incidence of tumor lysis syndrome in elderly patients with chronic lymphocytic leukemia treated with venetoclax under real-world conditions: results from the prospective observational VeRVe study.

Venetoclax is active in both frontline and relapsed/refractory settings for the treatment of chronic lymphocytic leukemia (CLL). Although the prevalence and severity of tumor lysis syndrome (TLS) are well characterized in clinical trials, laboratory and clinical TLS remain relatively unexplored in real-world clinical practice.In this prospective, real-world observational study, we aimed to determine the incidence and outcomes of TLS in patients with CLL receiving venetoclax outside a clinical trial.

Neratinib as Extended Adjuvant Treatment of HER2-Positive/HR-Positive Early Breast Cancer Patients in Germany, Austria, and Switzerland: Interim Results of the Prospective, Observational ELEANOR Study.

Introduction: Prognosis of patients diagnosed with HER2+ early breast cancer (eBC) has substantially improved, but distant recurrences impacting quality of life and survival still occur. One treatment option for extended adjuvant treatment of patients with HER2+/HR+ eBC is neratinib, available in Europe for patients who completed adjuvant trastuzumab-based therapy within 1 year. The ELEANOR study is investigating the real-world use of neratinib in Germany, Austria, and Switzerland.

Final Results from RIBBIT: A Randomized Phase III Study to Evaluate Efficacy and Quality of Life in Patients with Metastatic Hormone Receptor-Positive, HER2-Negative Breast Cancer Receiving Ribociclib in Combination with Endocrine Therapy or Chemotherapy with or without Bevacizumab in the First-Line Setting.

Background: We investigated the efficacy and health-related quality of life (HRQoL) in patients receiving either ribociclib plus endocrine therapy (ET) or chemotherapy with/without bevacizumab as first-line treatment of metastatic hormone receptor (HR)-positive, HER2-negative breast cancer (BC).

Patients And Methods: In this randomized, phase III study (RIBBIT), 38 patients diagnosed with metastatic HR-positive, HER2-negative BC with presence of visceral metastases recruited between May 2018 and December 2020 were randomly assigned in a 1:1 ratio to either arm A (ribociclib + ET) or arm B (chemotherapy with/without bevacizumab) at 12 sites in Germany. The primary endpoint was progression-free survival (PFS).

Comprehensive 7 T CEST: A clinical MRI protocol covering multiple exchange rate regimes.

Chemical exchange saturation transfer (CEST) is a magnetic resonance (MR) imaging method providing molecular image contrasts based on indirect detection of low concentrated solutes. Previous CEST studies focused predominantly on the imaging of single CEST exchange regimes (e.g.

Sidebands in CEST MR-How to recognize and avoid them.

Purpose: Clinical scanners require pulsed CEST sequences to maintain amplifier and specific absorption rate limits. During off-resonant RF irradiation and interpulse delay, the magnetization can accumulate specific relative phases within the pulse train. In this work, we show that these phases are important to consider, as they can lead to unexpected artifacts when no interpulse gradient spoiling is performed during the saturation train.

CCL19-Positive Lymph Node Stromal Cells Govern the Onset of Inflammatory Arthritis via Tropomyosin Receptor Kinase.

Objective: The study objective was to assess the role of CCL19 lymph node stromal cells of the joint-draining popliteal lymph node (pLN) for the development of arthritis.

Methods: CCL19 lymph node stromal cells were spatiotemporally depleted for five days in the pLN before the onset of collagen-induced arthritis (CIA) using Ccl19-Cre × iDTR mice. In addition, therapeutic treatment with recombinant CCL19-immunoglobulin G (IgG), locally injected in the footpad, was used to confirm the results.

Transcriptional reprogramming during human osteoclast differentiation identifies regulators of osteoclast activity.

Enhanced osteoclastogenesis and osteoclast activity contribute to the development of osteoporosis, which is characterized by increased bone resorption and inadequate bone formation. As novel antiosteoporotic therapeutics are needed, understanding the genetic regulation of human osteoclastogenesis could help identify potential treatment targets. This study aimed to provide an overview of transcriptional reprogramming during human osteoclast differentiation.

Fluid suppression in amide proton transfer-weighted (APTw) CEST imaging: New theoretical insights and clinical benefits.

Purpose: Amide proton transfer-weighted (APTw) MRI at 3T provides a unique contrast for brain tumor imaging. However, APTw imaging suffers from hyperintensities in liquid compartments such as cystic or necrotic structures and provides a distorted APTw signal intensity. Recently, it has been shown that heuristically motivated fluid suppression can remove such artifacts and significantly improve the readability of APTw imaging.

APT weighted imaging in diffuse gliomas.

Amide proton transfer-weighted (APTw) imaging is a non-invasive molecular MRI technique with a wide range of applications in neuroradiology and particularly neuro-oncology imaging. More than 15 years of pre-clinical experiments and clinical studies have demonstrated that APTw metrics are reproducible and reliable, leading to large-scale clinical acceptance. At present, major vendors of MRI scanners provide APTw sequences upon request.

Multi-parametric optimization of magnetic resonance imaging sequences for magnetic resonance-guided radiotherapy.

Background And Purpose: Magnetic Resonance Imaging (MRI) is widely used in oncology for tumor staging, treatment response assessment, and radiation therapy (RT) planning. This study proposes a framework for automatic optimization of MRI sequences based on pulse sequence parameter sets (SPS) that are directly applied on the scanner, for application in RT planning.

Materials And Methods: A phantom with seven in-house fabricated contrasts was used for measurements.

L-arginine metabolism inhibits arthritis and inflammatory bone loss.

Objectives: To investigate the effect of the L-arginine metabolism on arthritis and inflammation-mediated bone loss.

Methods: L-arginine was applied to three arthritis models (collagen-induced arthritis, serum-induced arthritis and human TNF transgenic mice). Inflammation was assessed clinically and histologically, while bone changes were quantified by μCT and histomorphometry.

Multi-echo-based fat artifact correction for CEST MRI at 7 T.

Purpose: CEST MRI is influenced by fat signal, which can reduce the apparent CEST contrast or lead to pseudo-CEST effects. Our goal was to develop a fat artifact correction based on multi-echo fat-water separation that functions stably for 7 T knee MRI data.

Methods: Our proposed algorithm utilizes the full complex data and a phase demodulation with an off-resonance map estimation based on the Z-spectra prior to fat-water separation to achieve stable fat artifact correction.

Alcohol-sourced acetate impairs T cell function by promoting cortactin acetylation.

Alcohol is among the most widely consumed dietary substances. Excessive alcohol consumption damages the liver, heart, and brain. Alcohol also has strong immunoregulatory properties.