Surgical and Endovascular Therapies for Below-the-Knee Peripheral Arterial Disease: A Contemporary Review.

Peripheral arterial disease (PAD) represents one of the most prevalent cardiovascular disease processes and carries a high burden of morbidity and mortality. Patients with chronic limb-threatening ischemia (CLTI), the most severe manifestation of PAD, have the highest rates of cardiovascular morbidity and mortality of the overall PAD population. Patients with below-the-knee (BTK) PAD have an increased propensity toward CLTI due to small-vessel caliber and the frequently comorbid conditions of end-stage renal disease and diabetes mellitus, which tend to affect small artery beds preferentially.

Exploring microtubule dynamics in Alzheimer's disease: Longitudinal assessment using [C]MPC-6827 PET imaging in rodent models of Alzheimer's-related pathology.

Introduction: Microtubule (MT) stability is crucial for proper neuronal function. Understanding MT dysregulation is critical for connecting amyloid beta (Aβ) and tau-based degenerative events and early changes in presymptomatic Alzheimer's disease (AD). Herein we present positron emission tomography (PET) imaging properties of our MT-PET radiotracer, [C]MPC-6827, in multiple established AD mouse models.

Small extracellular vesicles (sEVs)-based gene delivery platform for cell-specific CRISPR/Cas9 genome editing.

Small extracellular vesicles (sEVs) are naturally occurring vesicles that have the potential to be manipulated to become promising drug delivery vehicles for on-demand and gene editing. Here, we developed the modular safeEXO platform, a prototype sEV delivery vehicle that is mostly devoid of endogenous RNA and can efficaciously deliver RNA and ribonucleoprotein (RNP) complexes to their intended intracellular targets manifested by downstream biologic activity. We also successfully engineered producer cells to produce safeEXO vehicles that contain endogenous Cas9 (safeEXO-CAS) to effectively deliver efficient ribonucleoprotein (RNP)-mediated CRISPR genome editing machinery to organs or diseased cells and .

Focused ultrasound-mediated blood-brain barrier opening is safe and feasible with moderately hypofractionated radiotherapy for brainstem diffuse midline glioma.

Background: Diffuse midline glioma (DMG) is a pediatric tumor with dismal prognosis. Systemic strategies have been unsuccessful and radiotherapy (RT) remains the standard-of-care. A central impediment to treatment is the blood-brain barrier (BBB), which precludes drug delivery to the central nervous system (CNS).

Communication of Incidental Imaging Findings on Inpatient Discharge Summaries After Implementation of Electronic Health Record Notification System.

Objectives: Inadequate follow-up of incidental imaging findings (IIFs) can result in poor patient outcomes, patient dissatisfaction, and provider malpractice. At our institution, radiologists flag IIFs during report dictation to trigger electronic health record (EHR) notifications to providers and patients. Nurse coordinators directly contact patients or their primary care physicians (PCPs) regarding IIFs if follow-up is not completed within the recommended time frame.

Loss of Pip4k2c confers liver-metastatic organotropism through insulin-dependent PI3K-AKT pathway activation.

Liver metastasis (LM) confers poor survival and therapy resistance across cancer types, but the mechanisms of liver-metastatic organotropism remain unknown. Here, through in vivo CRISPR-Cas9 screens, we found that Pip4k2c loss conferred LM but had no impact on lung metastasis or primary tumor growth. Pip4k2c-deficient cells were hypersensitized to insulin-mediated PI3K/AKT signaling and exploited the insulin-rich liver milieu for organ-specific metastasis.

Percutaneous Transluminal Angioplasty for Infrapopliteal Chronic Limb-Threatening Ischemia: A Systematic Review and Meta-analysis of Primary Patency and Binary Restenosis Rates.

Purpose: Percutaneous transluminal angioplasty (PTA) remains the mainstay of endovascular therapy for infrapopliteal chronic limb-threatening ischemia (CLTI), but outcomes have not been well characterized using high-quality data. The aim of this meta-analysis was to provide an updated benchmark for rates of primary patency and binary restenosis after PTA using prospectively collected, predominantly core-lab adjudicated randomized controlled trial (RCT) data.

Materials And Methods: MEDLINE, EMBASE, Cochrane Central, and ClinicalTrials.

Preliminary PET Imaging of Microtubule-Based PET Radioligand [C]MPC-6827 in a Nonhuman Primate Model of Alzheimer's Disease.

The microtubule (MT) instability observed in Alzheimer's disease (AD) is commonly attributed to hyperphosphorylation of the MT-associated protein, tau. PET imaging offers an opportunity to gain critical information about MT changes with the onset and development of AD and related dementia. We developed the first brain-penetrant MT PET ligand, [C]MPC-6827, and evaluated its imaging utility in vervet monkeys.

CT-derived textural analysis parameters discriminate high-attenuation renal cysts from solid renal neoplasms.

Aim: To assess the utility of textural features on computed tomography (CT) to differentiate high-attenuation cysts from solid renal neoplasms among indeterminate renal lesions detected incidentally on CT.

Materials And Methods: Patients were included if they had an indeterminate renal lesion on CT that was subsequently characterised on ultrasound or magnetic resonance imaging (MRI). Up to three lesions per patient were included if they had a size ≥10 mm and density of 20-70 HU on unenhanced CT or any single phase of contrast-enhanced CT.

PET imaging of dopamine transporters and D2/D3 receptors in female monkeys: effects of chronic cocaine self-administration.

Brain imaging studies using positron emission tomography (PET) have shown that long-term cocaine use is associated with lower levels of dopamine (DA) D2/D3 receptors (D2/D3R); less consistent are the effects on DA transporter (DAT) availability. However, most studies have been conducted in male subjects (humans, monkeys, rodents). In this study, we used PET imaging in nine drug-naïve female cynomolgus monkeys to determine if baseline measures of DAT, with [F]FECNT, and D2/D3R availability, with [C]raclopride, in the caudate nucleus, putamen and ventral striatum were associated with rates of cocaine self-administration and if these measures changed during long-term (~13 months) cocaine self-administration and following time-off (3-9 months) from cocaine.

Binding Parameters of [C]MPC-6827, a Microtubule-Imaging PET Radiopharmaceutical in Rodents.

Impairment and/or destabilization of neuronal microtubules (MTs) resulting from hyper-phosphorylation of the tau proteins is implicated in many pathologies, including Alzheimer's disease (AD), Parkinson's disease and other neurological disorders. Increasing scientific evidence indicates that MT-stabilizing agents protect against the deleterious effects of neurodegeneration in treating AD. To quantify these protective benefits, we developed the first brain-penetrant PET radiopharmaceutical, [C]MPC-6827, for quantification of MTs in rodent and nonhuman primate models of AD.

SP140 inhibits STAT1 signaling, induces IFN-γ in tumor-associated macrophages, and is a predictive biomarker of immunotherapy response.

Background: Understanding the role and potential therapeutic targeting of tumor-associated macrophages (TAMs) is crucial to developing new biomarkers and therapeutic strategies for cancer immunotherapies. The epigenetic reader SP140 has emerged as a master regulator of macrophage transcriptional programs; however, its role in the signaling of TAMs and response to immunotherapy has not been investigated.

Methods: We evaluated the correlation between SP140 expression in head and neck squamous cell carcinoma (HNSCC) TAMs and clinical outcomes.

[F]KS1, a novel ascorbate-based ligand images ROS in tumor models of rodents and nonhuman primates.

Over production of reactive oxygen species (ROS) caused by altered redox regulation of signaling pathways is common in many types of cancers. While PET imaging is recognized as the standard tool for cancer imaging, there are no clinically-approved PET radiotracers for ROS-imaging in cancer diagnosis and treatment. An ascorbate-based radio ligand promises to meet this urgent need.

Preliminary efficacy of [Y]DOTA-biotin-avidin radiotherapy against non-muscle invasive bladder cancer.

Purpose: Bladder cancer represents 3% of all new cancer diagnoses per year. We propose intravesical radionuclide therapy using the β-emitter Y linked to DOTA-biotin-avidin ([Y]DBA) to deliver short-range radiation against non-muscle invasive bladder cancer (NMIBC).

Material And Methods: Image-guided biodistribution of intravesical DBA was investigated in an animal model by radiolabeling DBA with the Ga and dynamic microPET imaging following intravesical infusion of [Ga]DBA for up to 4 h and post-necropsy γ-counting of organs.

Advancements in drug delivery methods for the treatment of brain disease.

The blood-brain barrier (BBB) presents a formidable obstacle to the effective delivery of systemically administered pharmacological agents to the brain, with ~5% of candidate drugs capable of effectively penetrating the BBB. A variety of biomaterials and therapeutic delivery devices have recently been developed that facilitate drug delivery to the brain. These technologies have addressed many of the limitations imposed by the BBB by: (1) designing or modifying the physiochemical properties of therapeutic compounds to allow for transport across the BBB; (2) bypassing the BBB by administration of drugs alternative routes; and (3) transiently disrupting the BBB (BBBD) using biophysical therapies.

The Effects of Rudeness on NICU Medical Teams Studied by a New Tool for the Assessment of Decision-Making Group Dynamics.

Background: Group decision-making can be placed on a continuum of group dynamics, between Groupthink and Polythink.

Objective: To present a new assessment tool for the characterization of medical teams' decision-making group dynamics, and test it to study the effects of exposure to rudeness on various types of group dynamics.

Methods: Three judges who watched videotapes of critical care simulations evaluated 24 neonatal intensive care unit teams' decision-making processes.

Chronic convection-enhanced delivery of topotecan for patients with recurrent glioblastoma: a first-in-patient, single-centre, single-arm, phase 1b trial.

Background: Topotecan is cytotoxic to glioma cells but is clinically ineffective because of drug delivery limitations. Systemic delivery is limited by toxicity and insufficient brain penetrance, and, to date, convection-enhanced delivery (CED) has been restricted to a single treatment of restricted duration. To address this problem, we engineered a subcutaneously implanted catheter-pump system capable of repeated, chronic (prolonged, pulsatile) CED of topotecan into the brain and tested its safety and biological effects in patients with recurrent glioblastoma.