Transcutaneous Ablation of Lung Tissue in a Porcine Model Using Magnetic-Resonance-Guided Focused Ultrasound (MRgFUS).

Focused ultrasound (FUS) is a minimally invasive treatment that utilizes high-energy ultrasound waves to thermally ablate tissue. Magnetic resonance imaging (MRI) guidance may be combined with FUS (MRgFUS) to increase its accuracy and has been proposed for lung tumor ablation/debulking. However, the lungs are predominantly filled with air, which attenuates the strength of the FUS beam. This investigation aimed to test the feasibility of a new approach using an intentional lung collapse to reduce the amount of air inside the lung and a controlled hydrothorax to create an acoustic window for transcutaneous MRgFUS lung ablation. Eleven pigs had one lung mechanically ventilated while the other lung underwent a controlled collapse and subsequent hydrothorax of that hemisphere. The MRgFUS lung ablations were then conducted via the intercostal space. All the animals recovered well and remained healthy in the week following the FUS treatment. The location and size of the ablations were confirmed one week post-treatment via MRI, necropsy, and histological analysis. The animals had almost no side effects and the skin burns were completely eliminated after the first two animal studies, following technique refinement. This study introduces a novel methodology of MRgFUS that can be used to treat deep lung parenchyma in a safe and viable manner.

Traumatic brain injury is common and undertreated in the orthopaedic trauma population.

INTRODUCTION: Traumatic brain injuries (TBIs) can be difficult to diagnose and are often marginalized when compared to more obvious physical injuries. Despite this, recognition and early treatment can lead to improved outcomes. Even mild TBIs have the potential to cause significant long-term consequences for patients, which may affect their physical recovery from orthopaedic injuries. The objective of this study was to examine the incidence and treatment of TBI within the orthopaedic trauma population. METHODS: Inclusion criteria were all patients presenting after an acute trauma with an orthopaedic surgery consult over a continuous 3 month timeframe (n = 187). A retrospective review was completed at an academic tertiary referral trauma center. The primary outcome was the rate of TBI. Secondary outcomes included rate of TBI listed as a discharge diagnosis and rate of follow up plan. Several secondary variables were noted and their associations with TBI evaluated. RESULTS: 27 % of the 187 patients had an acute TBI. 61 % of TBI patients had the diagnosis listed in their discharge summary. 6 % had a follow up plan. The positive TBI group was associated with more high energy injuries (p = 0.032), average limbs involved (p = 0.007), upper extremity injury (p < 0.001), bilateral lower extremity injury (p = 0.004), and Injury Severity Score (p < 0.001). 82 % of patients with an acute TBI had an occupational therapy consult and 39 % had a neurosurgery consult. 24 % of patients with a TBI were admitted to the orthopaedic primary service. CONCLUSIONS: Patients presenting after an acute trauma with orthopaedic injuries have high rates of TBI, but low rates of diagnosis and treatment. This lack of diagnosis and treatment can negatively impact recovery from orthopaedic injuries. Orthopaedic providers should be aware of the diagnostic criteria and initial treatment steps for TBI to ensure prompt and effective treatment, which has been shown to improve outcomes.

3D Single-Breath Chemical Shift Imaging Hyperpolarized Xe-129 MRI of Healthy, CF, IPF, and COPD Subjects.

3D Single-breath Chemical Shift Imaging (3D-SBCSI) is a hybrid MR-spectroscopic imaging modality that uses hyperpolarized xenon-129 gas (Xe-129) to differentiate lung diseases by probing functional characteristics. This study tests the efficacy of 3D-SBCSI in differentiating physiology among pulmonary diseases. A total of 45 subjects-16 healthy, 11 idiopathic pulmonary fibrosis (IPF), 13 cystic fibrosis (CF), and 5 chronic obstructive pulmonary disease (COPD)-were given 1/3 forced vital capacity (FVC) of hyperpolarized Xe-129, inhaled for a ~7 s MRI acquisition. Proton, Xe-129 ventilation, and 3D-SBCSI images were acquired with separate breath-holds using a radiofrequency chest coil tuned to Xe-129. The Xe-129 spectrum was analyzed in each lung voxel for ratios of spectroscopic peaks, chemical shifts, and T2* relaxation. CF and COPD subjects had significantly more ventilation defects than IPF and healthy subjects, which correlated with FEV1 predicted (R = -0.74). FEV1 predicted correlated well with RBC/Gas ratio (R = 0.67). COPD and IPF had significantly higher Tissue/RBC ratios than other subjects, longer RBC T2* relaxation times, and greater RBC chemical shifts. CF subjects had more ventilation defects than healthy subjects, elevated Tissue/RBC ratio, shorter Tissue T2* relaxation, and greater RBC chemical shift. 3D-SBCSI may be helpful in the detection and characterization of pulmonary disease, following treatment efficacy, and predicting disease outcomes.

Extracellular Vesicles and Chemotherapy Resistance in the AML Microenvironment.

Extracellular vesicle (EV) trafficking provides for a constitutive mode of cell-cell communication within tissues and between organ systems. Different EV subtypes have been identified that transfer regulatory molecules between cells, influencing gene expression, and altering cellular phenotypes. Evidence from a range of studies suggests that EV trafficking enhances cell survival and resistance to chemotherapy in solid tumors. In acute myeloid leukemia (AML), EVs contribute to the dynamic crosstalk between AML cells, hematopoietic elements and stromal cells and promote adaptation of compartmental bone marrow (BM) function through transport of protein, RNA, and DNA. Careful analysis of leukemia cell EV content and phenotypic outcomes provide evidence that vesicles are implicated in transferring several known key mediators of chemoresistance, including miR-155, IL-8, and BMP-2. Here, we review the current understanding of how EVs exert their influence in the AML niche, and identify research opportunities to improve outcomes for relapsed or refractory AML patients.