Breast Arterial Calcifications on Mammography: Awareness and Reporting Preferences Amongst Referring Physicians in Canada.

Purpose: Breast arterial calcifications (BAC) on mammography have been correlated with increased cardiovascular risk. The Canadian Society of Breast Imaging released a position statement on BAC reporting in January 2023. This study evaluates the awareness of the clinical significance of BAC and reporting preferences of referring physicians in Canada. Methods: A 15-question survey was distributed to Canadian physicians who may review mammography results via regional and subspecialty associations and on social media following local institutional ethical approval. Responses were collected over 10 weeks from February to April 2023. Results: Seventy-two complete responses were obtained. We are unable to determine the response rate, given the means of distribution. Only 17% (12/72) of responding physicians were previously aware of the association between BAC and increased cardiovascular risk, and 51% (37/72) preferred the inclusion of BAC in the mammography report. Fifty-six percent (40/72) indicated that BAC reporting would prompt further investigation, and 63% (45/72) would inform patients that their mammogram showed evidence of BAC. Sixty-nine percent (50/72) would find grading of BAC beneficial and 71% (51/72) agreed that there is a need for national guidelines. Conclusion: Less than a quarter of responding Canadian referring physicians were previously aware of the association between BAC and cardiovascular risk, although half of respondents indicated a preference for BAC reporting on mammography. Most participating physicians would inform their patients of the presence of BAC and consider further cardiovascular risk management. There was consensus that a national BAC grading system and clinical management guidelines would be beneficial.

Retrospective Evaluation of Splenic Artery Embolization Outcomes in the Management of Blunt Splenic Trauma: A Single Centre Experience at a Large Level 1 Trauma Centre.

PURPOSE: Retrospective review of splenic artery embolization (SAE) outcomes performed for blunt abdominal trauma. MATERIALS AND METHODS: 11-year retrospective review at a large level-1 Canadian trauma centre. All patients who underwent SAE after blunt trauma were included. Technical success was defined as angiographic occlusion of the target vessel and clinical success was defined as successful non-operative management and splenic salvage on follow-up. RESULTS: 138 patients were included of which 68.1% were male. The median age was 47 years (interquartile range (IQR) = 32.5 years). The most common mechanisms of injury were motor vehicle accidents (37.0%), mechanical falls (25.4%), and pedestrians hit by motor vehicles (10.9%). 70.3% of patients had American Association for the Surgery of Trauma (AAST) grade 4 injuries. Patients were treated with proximal SAE (n = 97), distal SAE (n = 23) or combined SAE (n = 18), and 68% were embolized with an Amplatzer plug. No significant differences were observed across all measures of hospitalization (Length of hospital stay: x2(2) = .358, P = .836; intensive care unit (ICU) stay: x2(2) = .390, P = .823; ICU stay post-procedure: x2(2) = 1.048, P = .592). Technical success and splenic salvage were achieved in 100% and 97.8% of patients, respectively. 7 patients (5%) had post-embolization complications and 7 patients (5%) died during hospital admission, but death was secondary to other injuries sustained in the trauma rather than complications related to splenic injury or its management. CONCLUSION: We report that SAE as an adjunct to non-operative management of blunt splenic trauma can be performed safely and effectively with a high rate of clinical success.

Correlation Between Breast Arterial Calcifications and Higher Cardiovascular Risk: Awareness and Attitudes Amongst Canadian Radiologists Who Report Mammography.

Background: Breast arterial calcification (BAC) on mammography correlates with increased cardiovascular risk. Reporting BAC is not standard practice. Our study evaluates the awareness of Canadian radiologists who report mammography of the clinical significance of BAC and their attitudes towards reporting BAC compared to their European and American counterparts. Methods: Following local institutional ethics approval, a 25 question survey (SurveyMonkey) was disseminated to Canadian radiologists via provincial and national society email lists. Responses were collected over 5 weeks (April-June 2022). Results: One hundred and eighty-six complete responses were collected. Sixty percent (112/186) were aware of the association between BAC and cardiovascular risk and 16% (29/186) document its presence in mammogram reports. Thirty five percent (65/186) occasionally document BAC if severe or in a young patient. Four percent (7/186) had local departmental guidelines on BAC reporting and 82% (153/186) agreed there is a need for national BAC reporting guidelines. Fewer Canadian radiologists were aware of the association between BAC and cardiovascular risk compared to European radiologists (60% vs 81%), report the presence of BAC compared to both European (15% vs 62%) and American (15% vs 35%) radiologists, and inform the patient of the presence of BAC compared to European radiologists (1% vs 46%). Conclusion: Canadian radiologists who report mammography were less aware of the association between BAC and cardiovascular risk than their European and American counterparts and were less likely to document the presence of BAC. Given the correlation of BAC with increased cardiovascular event risk, there is increased need for awareness as well as national BAC reporting guidelines.

PHASE 2 RANDOMIZED STUDY (ORION-1) OF A NOVEL, BIODEGRADABLE DEXAMETHASONE IMPLANT (AR-1105) FOR THE TREATMENT OF MACULAR EDEMA DUE TO CENTRAL OR BRANCH RETINAL VEIN OCCLUSION.

PURPOSE: AR-1105 is a novel biodegradable sustained-release dexamethasone implant designed to deliver 6-month durability. This Phase 2 study evaluated two AR-1105 formulations with different release profiles in patients with macular edema due to retinal vein occlusion. METHODS: Patients received a single intravitreal injection with 340 µg dexamethasone. In the initial phase, five patients received clinical formulation (CF) 1. In the randomized phase, 44 patients were randomized 1:1 to CF1 or CF2. The follow-up was 6 months. Patients had vision loss due to macular edema diagnosed ≥9 (central retinal vein occlusion) or ≥12 months (branch retinal vein occlusion) before screening, and could be treatment-naive or -experienced (if received prior steroids, must have demonstrated response). RESULTS: Both formulations improved vision and reduced retinal thickening from baseline across all visits. At Month 6, mean changes in best-corrected visual acuity were +4.3 and +8.0 letters, and mean changes in central subfield thickness were -93 µm and -211 µm in CF1 and CF2 randomized patients, respectively. Most common adverse events were reduced visual acuity, worsening macular edema, conjunctival hemorrhage, and increased intraocular pressure. No patients required surgery or laser for intraocular pressure control. CONCLUSION: Both formulations were well tolerated and demonstrated clinically meaningful and sustained improvements in vision and retinal thickening in patients with retinal vein occlusion with longstanding edema.

Long-term gene expression in dividing and nondividing cells using SV40-derived vectors.

Among the goals of gene therapy is long-term expression of delivered transgenes. Recombinant Tagdeleted SV40 vectors (rSV40s) are especially well suited for this purpose. rSV40s deliver transgene expression that endures for extended periods of time in tissue culture and in vivo, in both dividing and nondividing cells. These vectors are particularly effective in transducing some cell types that have been almost unapproachable using other gene delivery systems, such as quiescent hematopoietic progenitor cells and their differentiated derivatives. Other cellular targets include neurons, brain microglia, hepatocytes, dendritic cells, vascular endothelium, and others. Because rSV40s do not elicit neutralizing antibodies they are useful for in vivo gene delivery in settings where more than one administration may be desirable. The key characteristics of these vectors include their high production titers and therefore suitability for large cell pools, effectiveness in delivering intracellular proteins, and untranslated RNAs, maintenance of transgene expression at constant levels for extended times, suitability for constitutive or conditional promoters and for combinatorial gene delivery and ability to integrate into genomes of both dividing and nondividing cells.

What they are, how they work and why they do what they do? The story of SV40-derived gene therapy vectors and what they have to offer.

The natural function of viruses is to deliver their genetic material to cells. Among the most effective of viruses in doing that is Simian Virus-40 (SV40). The properties that make SV40 a successful virus make it an attractive candidate for use as a gene delivery vehicle: high titer replication, infectivity for almost all nucleated cell types whether the cells are dividing or resting, potential for integration into cellular DNA, a peculiar pathway for entering cells that bypasses the cells' antigen processing apparatus, very high stability, and the apparent ability to activate expression of its own capsid genes in trans. Exploiting these and other characteristics of wild type (wt) SV40, increasing numbers of laboratories are studying recombinant (r) SV40-derived vectors. Among the uses to which these vectors have been applied are: delivering therapy to inhibit HIV, hepatitis C virus (HCV) and other viruses; correction of inherited hepatic and other protein deficiencies; immunizing against lentiviral and other antigens; treatment of inherited and acquired diseases of the central nervous system; protecting the lung and other organs from free radical-induced injury; and many others. The effectiveness of these vectors is a reflection of the adaptive evolution that produced their parent virus, wt SV40. This article explores how and why these vectors work, their strengths and their limitations, and provides a functional model for their exploitation for experimental and clinical applications.

Immune responses against SIV envelope glycoprotein, using recombinant SV40 as a vaccine delivery vector.

Vaccination protocols using viral gene delivery vectors have often generated relatively weak responses, largely owing to difficulties in boosting immune responses effectively following the primary injection. Because recombinant gene delivery vectors derived from SV40 permit multiple inoculations, to yield incremental immune responses, we tested the use of rSV40s to deliver lentiviral envelope antigens for immunization. An rSV40 carrying SIVmac239 envelope glycoprotein gp130 cDNA (SV(gp130)) was given multiple times to BALB/c mice, with or without a prior priming inoculation using vaccinia virus carrying the same SIV envelope cDNA (VVenvSIV). Sera from these mice were tested for antibodies binding gp130, applying a novel cell-based ELISA protocol that used as targets cloned P815 cells stably transfected with plasmid-derived gp130 cDNA. The same gp130-expressing clone of P815 cells, labeled with 51Cr was used as targets for direct lymphocyte-mediated cytolytic assays using spleen and popliteal lymph node cells as effectors. After six inoculations with SV(gp130), mice made detectable anti-gp130 antibody responses, but high levels of splenic and popliteal lymph node cytotoxic activity were apparent after as few as three injections of SV(gp130) (>40% specific lysis). A single primary inoculation with VVenvSIV preceding SV(gp130) boosts significantly enhanced antibody responses against SIV gp130, but had little effect on cytotoxic lymphocyte responses. Thus, rSV40 vectors may be useful vehicles for delivering lentiviral envelope antigens to elicit protective humoral and cell-mediated immune responses.