A Systematic Review and Meta-Analysis of Drug Eluting Stents for Safety and Efficacy in Intracranial Atherosclerotic Disease.

BACKGROUND: Advancements in arterial stenting technology have challenged prior notions favoring medical management for intracranial atherosclerotic disease (ICAD). Where previous conclusions were drawn from bare metal stent (BMS) technology, recent studies suggest drug-eluting stents (DES) are favorable due to their anti-proliferative effect, which reduces vascular remodeling. METHODS: We conducted a systematic review and meta-analysis of the literature prior to August 2023 reviewing all reports of ICAD treated with DES. Our target outcomes were incidence of any stroke, transient ischemic attack (TIA), or death within 30 days (postprocedural complications), ischemic stroke in the territory of the qualifying artery beyond 30 days (long-term complications), radiographically detected in-stent restenosis rate (ISR), and symptomatic ISR during follow-up. A subgroup analysis further stratified preprocedural mean stenosis above and below 70% into severe and moderate cohorts, respectively. RESULTS: PubMed, Web of Science, Cochrane and EMBASE query identified 527 candidate articles, from which 14 studies met inclusion criteria for a total of 607 patients and 640 ICAD lesions. Incidence of postprocedural complications was 7.3% (95% CI 3.9-11.7%) with subgroup analysis demonstrating significantly higher incidence in the severely stenotic group [9.0% (95% CI 4.7-14.5%)] than the moderately stenotic group [3.0% (95% CI 0.7-6.8%)]. Long-term complications were 1.2% (95% CI 0.4-2.3%). Radiographic ISR was 3.5% (95% CI 1.4-6.3%) and symptomatic ISR was 0.3% (95% CI 0.0-1.5%). CONCLUSIONS: Our systematic review and meta-analysis suggest that DES can effectively reduce the risk of ISR and may be a viable treatment modality to reduce long-term complications in refractory ICAD patients.

Lysosomal LRRC8 complex regulates lysosomal pH, morphology and systemic glucose metabolism.

The lysosome integrates anabolic signalling and nutrient-sensing to regulate intracellular growth pathways. The leucine-rich repeat containing 8 (LRRC8) channel complex forms a lysosomal anion channel and regulates PI3K-AKT-mTOR signalling, skeletal muscle differentiation, growth, and systemic glucose metabolism. Here, we define the endogenous LRRC8 subunits localized to a subset of lysosomes in differentiated myotubes. We show LRRC8A regulates leucine-stimulated mTOR, lysosome size, number, pH, and expression of lysosomal proteins LAMP2, P62, LC3B, suggesting impaired autophagic flux. Mutating a LRRC8A lysosomal targeting dileucine motif sequence (LRRC8A-L706A;L707A) in myotubes recapitulates the abnormal AKT signalling and altered lysosomal morphology and pH observed in LRRC8A KO cells. In vivo , LRRC8A-L706A;L707A KI mice exhibit increased adiposity, impaired glucose tolerance and insulin resistance characterized by reduced skeletal muscle glucose-uptake, and impaired incorporation of glucose into glycogen. These data reveal a lysosomal LRRC8 mediated metabolic signalling function that regulates lysosomal activity, systemic glucose homeostasis and insulin-sensitivity.

LRRC8 complexes are adenosine nucleotide release channels regulating platelet activation and arterial thrombosis.

Platelet shape and volume changes are early mechanical events contributing to platelet activation and thrombosis. Here, we identify single-nucleotide polymorphisms in Leucine-Rich Repeat Containing 8 (LRRC8) protein subunits that form the Volume-Regulated Anion Channel (VRAC) which are independently associated with altered mean platelet volume. LRRC8A is required for functional VRAC in megakaryocytes (MKs) and regulates platelet volume, adhesion, and agonist-stimulated activation, aggregation, ATP secretion and calcium mobilization. MK-specific LRRC8A cKO mice have reduced arteriolar thrombus formation and prolonged arterial thrombosis without affecting bleeding times. Mechanistically, platelet LRRC8A mediates swell-induced ATP/ADP release to amplify agonist-stimulated calcium and PI3K-AKT signaling via P2X1, P2Y 1 and P2Y 12 receptors. Small-molecule LRRC8 channel inhibitors recapitulate defects observed in LRRC8A-null platelets in vitro and in vivo . These studies identify the mechanoresponsive LRRC8 channel complex as an ATP/ADP release channel in platelets which regulates platelet function and thrombosis, providing a proof-of-concept for a novel anti-thrombotic drug target.

3D printing exposure and perception in radiology residency: survey results of radiology chief residents.

RATIONALE AND OBJECTIVES: The purpose of this study is to summarize a survey of radiology chief residents focused on 3D printing in radiology. MATERIALS AND METHODS: An online survey was distributed to chief residents in North American radiology residencies by subgroups of the Association of University Radiologists. The survey included a subset of questions focused on the clinical use of 3D printing and perceptions of the role of 3D printing and radiology. Respondents were asked to define the role of 3D printing at their institution and asked about the potential role of clinical 3D printing in radiology and radiology residencies. RESULTS: 152 individual responses from 90 programs were provided, with a 46% overall program response rate (n = 90/194 radiology residencies). Most programs had 3D printing at their institution (60%; n = 54/90 programs). Among the institutions that perform 3D printing, 33% (n = 18/54) have structured opportunities for resident contribution. Most residents (60%; n = 91/152 respondents) feel they would benefit from 3D printing exposure or educational material. 56% of residents (n = 84/151) believed clinical 3D printing should be centered in radiology departments. 22% of residents (n = 34/151) believed it would increase communication and improve relationships between radiology and surgery colleagues. A minority (5%; 7/151) believe 3D printing is too costly, time-consuming, or outside a radiologist's scope of practice. CONCLUSIONS: A majority of surveyed chief residents in accredited radiology residencies believe they would benefit from exposure to 3D printing in residency. 3D printing education and integration would be a valuable addition to current radiology residency program curricula.

Pilot Study on the Influence of Incentive Spirometry on Percutaneous Image-Guided Intra-Abdominal Drainage Catheter Pressure: A Potential Method to Enhance Drainage.

Background: To report the evaluation of incentive spirometry (IS)-induced pressure changes in intra-abdominal drainage catheters and consider its use for maintaining catheter patency and enhancing drainage. Methods: Prospective study of patients with indwelling intra-abdominal drainage catheters for abdominal fluid collections who had their intra-abdominal pressures measured while performing incentive spirometry. Patients were instructed in the use of an incentive spirometer. Within a week after initial drainage, pressure changes with IS were evaluated three times at 1500 cc and three times at maximum inspiratory effort. Intra-abdominal pressure (IAP) was measured using a pressure monitor connected to the drainage catheter. Results: Twenty patients (men, 12; women, 8). Fluid collection locations were pelvis, Right-upper quadrant (RUQ), Left-upper quadrant (LUQ), Left-lower quadrant (LLQ), and Right-lower quadrant (RLQ). A total of 16 of 20 patients showed an elevation of IAP with IS. At 1500 cc, the pressure increased by an average of 41.24 mmH2O. At maximal inspiratory effort, the pressure increased by an average of 48.26 mmH2O. Pressure increase was greater in upper abdomen catheters. Four patients with lower abdominal and pelvic collections showed minimal pressure changes with IS. Conclusion: IS increases IAP and fluid flow through abdominal drainage catheters. Future studies are warranted to determine whether the use of IS enhances catheter performance and facilitates drainage via its effect on IAP.