Citations

BackgroundDistortion‐free, high‐resolution diffusion imaging using DIADEM (Distortion‐free Imaging: A Double Encoding Method), proposed recently, has great potential for clinical applications. However, it can suffer from prolonged scan times and its reliability for quantitative diffusion imaging has not been evaluated.PurposeTo investigate the clinical feasibility of DIADEM‐based high‐resolution diffusion imaging on a novel compact 3T (C3T) by evaluating the reliability of quantitative diffusion measurements and utilizing both the high‐performance gradients (80 mT/m, 700 T/m/s) and the sequence optimization with the navigator acquisition window reduction and simultaneous multislice (multiband) imaging.Study TypeProspective feasibility study.Phantom/SubjectsDiffusion quality control phantom scans to evaluate the reliability of quantitative diffusion measurements; 36 normal control scans for B0‐field mapping; six healthy and two patient subject scans with a brain tumor for comparisons of diffusion and anatomical imaging.Field Strength/Sequence3T; the standard single‐shot echo‐planar‐imaging (EPI), multishot DIADEM diffusion, and anatomical (2D‐FSE [fast‐spin‐echo], 2D‐FLAIR [fluid‐attenuated‐inversion‐recovery], and 3D‐MPRAGE [magnetization prepared rapid acquisition gradient echo]) imaging.AssessmentThe scan time reduction, the reliability of quantitative diffusion measurements, and the clinical efficacy for high‐resolution diffusion imaging in healthy control and brain tumor volunteers.Statistical TestBland–Altman analysis.ResultsThe scan time for high in‐plane (0.86 mm2) resolution, distortion‐free, and whole brain diffusion imaging were reduced from 10 to 5 minutes with the sequence optimizations. All of the mean apparent diffusion coefficient (ADC) values in phantom were within the 95% confidence interval in the Bland–Altman plot. The proposed acquisition with a total off‐resonance coverage of 597.2 Hz wider than the expected bandwidth of 500 Hz in human brain could yield a distortion‐free image without foldover artifacts. Compared with EPI, therefore, this approach allowed direct image matching with the anatomical images and enabled improved delineation of the tumor boundaries.Data ConclusionThe proposed high‐resolution diffusion imaging approach is clinically feasible on C3T due to a combination of hardware and sequence improvements.Level of Evidence3Technical EfficacyStage 1 J. Magn. Reson. Imaging 2020;51:296–310.

Abstract Targeting the B-cell receptor and phosphatidylinositol 3-kinase/mTOR signaling pathways has shown meaningful, but incomplete, antitumor activity in lymphoma. Glycogen synthase kinase 3 (GSK3) α and β are 2 homologous and functionally overlapping serine/threonine kinases that phosphorylate multiple protein substrates in several key signaling pathways. To date, no agent targeting GSK3 has been approved for lymphoma therapy. We show that lymphoma cells abundantly express GSK3α and GSK3β compared with normal B and T lymphocytes at the messenger RNA and protein levels. Utilizing a new GSK3 inhibitor 9-ING-41 and by genetic deletion of GSK3α and GSK3β genes using CRISPR/CAS9 knockout, GSK3 was demonstrated to be functionally important to lymphoma cell growth and proliferation. GSK3β binds to centrosomes and microtubules, and lymphoma cells treated with 9-ING-41 become arrested in mitotic prophase, supporting the notion that GSK3β is necessary for the progression of mitosis. By analyzing recently published RNA sequencing data on 234 diffuse large B-cell lymphoma patients, we found that higher expression of GSK3α or GSK3β correlates well with shorter overall survival. These data provide rationale for testing GSK3 inhibitors in lymphoma patient trials.

Humans are sexually dimorphic, with sex being the most persistent difference among humans over the course of our evolutionary history. Beyond the visible sex differences that can be considered true dimorphisms, there are also sex differences at the molecular and cellular scales. The role of these biological sex differences for human health, while being increasingly recognized, have long been underappreciated and underexplored. Frequently, these differences are only recognized in sex–specific diseases, such as genitourinary diseases and cancers. However, given the evidence for sex differences in the most basic aspects of human biology, including metabolism, cellular composition, and immune activity, these differences could have consequences for the etiology and pathophysiology of a majority of diseases. It is thus essential to consider the extent to which these differences may influence the various mechanisms underlying disease processes, response to treatment, and the maintenance of health in order to better improve patient outcomes. Here we review the evidence for a broad array of biological sex differences in humans and discuss how they may relate to observed sex differences in various diseases, with an emphasis on cancer, specifically glioblastoma. We further propose that mathematical approaches can be useful for exploring the extent to which sex differences affect disease outcomes and accounting for those in the development of therapeutic strategies.

Objective The objective of this article is to evaluate the outcomes and complication rate for Adams–Berger anatomic reconstruction of the distal radioulnar joint (DRUJ), in addition, to determine the role of sigmoid notch anatomy on failure. Methods We conducted a retrospective chart review to evaluate adult patients that had undergone reconstruction of the DRUJ for instability with the Adams–Berger procedure between 1998 and 2015 within our institution with > 24 months follow-up. Charts were reviewed for patient demographics, mechanism of injury, outcome, and complications. Results Ninety-five wrists in 93 patients were included. Mean age at surgery was 37.3 years with 65.2 months follow-up. At the last follow-up, 90.8% had a stable DRUJ, 5.3% did not, and 3.4% had some laxity. Postoperatively, 75.9% described either no pain or mild pain. Grip strength increased while pronosupination decreased. Procedure success was 86.3%, as 12 patients underwent revision at 13.3 months postoperatively. Reconstructive failure was more common in females when an interference screw was utilized for tendon fixation. Age, timing of surgery, type of graft, sigmoid notch anatomy, and previous surgery did not affect revision or failure rate. Conclusion Our findings demonstrate that Adams–Berger reconstruction of the DRUJ provides reliable long-term results with an overall success of 86% at > 5 years follow-up. Level of evidence/Type of study This is a Level IV, therapeutic study.