HSV1716 Prevents Myeloma Cell Regrowth When Combined with Bortezomib In Vitro and Significantly Reduces Systemic Tumor Growth in Mouse Models.

Multiple myeloma remains largely incurable due to refractory disease; therefore, novel treatment strategies that are safe and well-tolerated are required. Here, we studied the modified herpes simplex virus HSV1716 (SEPREHVIR®), which only replicates in transformed cells. Myeloma cell lines and primary patient cells were infected with HSV1716 and assessed for cell death using propidium iodide (PI) and Annexin-V staining and markers of apoptosis and autophagy by qPCR. Myeloma cell death was associated with dual PI and Annexin-V positivity and increased expression of apoptotic genes, including CASP1, CASP8, CASP9, BAX, BID, and FASL. The combination of HSV1716 and bortezomib treatments prevented myeloma cell regrowth for up to 25 days compared to only transient cell growth suppression with bortezomib treatment. The viral efficacy was tested in a xenograft (JJN-3 cells in NSG mice) and syngeneic (murine 5TGM1 cells in C57BL/KaLwRijHsd mice) systemic models of myeloma. After 6 or 7 days, the post-tumor implantation mice were treated intravenously with the vehicle or HSV1716 (1 × 107 plaque forming units/1 or 2 times per week). Both murine models treated with HSV1716 had significantly lower tumor burden rates compared to the controls. In conclusion, HSV1716 has potent anti-myeloma effects and may represent a novel therapy for multiple myeloma.

pCONUS 2 and pCONUS 2-HPC in the treatment of wide-necked intracranial aneurysms: Multicentre UK experience.

BACKGROUND/PURPOSE: pCONUS 2 and pCONUS 2-HPC are neck-bridging devices that provide coiling support in the endovascular treatment of wide-necked intracranial aneurysms. To date, limited multicentre data has been published. This study provides the first pooled data from multiple UK centres regarding outcomes for these devices covering the periprocedural period to 6-month follow-up. MATERIALS/METHODS: This retrospective, single-arm study assessed 65 patients treated over 3 years from the time of procedure to 6 months post-procedure across four UK centres. Data collected included patient demographics, aneurysm characteristics and antiplatelet regimens. Outcome measures were angiographic results and procedure-related complications from the immediate periprocedural period to 6-month follow-up. RESULTS: Fifty-four unruptured (83.1%) and 11 ruptured (16.9%) aneurysms were treated. Fifty-five aneurysms were located in the anterior circulation (87.7%). There were four device-related intraprocedural complications: three cases of asymptomatic, temporary thrombus formation and one mortality associated with branch vessel occlusion and aneurysm re-bleeding in a ruptured case. There were no post-procedural device-related complications. Satisfactory occlusion was achieved in 58/65 procedures (89.2%) at time of treatment and in 44/60 (73.3%) at 6 months. Satisfactory occlusion correlated with aneurysm size and coiling packing density. Retreatment was required for five unruptured cases (7.7%) and was straightforward with the device in situ. CONCLUSION: pCONUS 2 and pCONUS 2-HPC have good short-term safety profiles. The use of pCONUS 2-HPC in the acute treatment of ruptured aneurysms with postprocedural SAPT is feasible. The devices have an intraprocedural complication rate of 4/65 (6.2%) across multiple UK centres, including a single death (1.5%).

Pulmonary migration of liquid embolization material: An unusual cause of pulmonary embolism.

Iatrogenic non-thrombotic pulmonary embolism is a rare cause of pulmonary embolism. This case demonstrates the unusual imaging findings associated with pulmonary migration of Precipitating Hydrophobic Injectable Liquid, a liquid embolization material most commonly used in interventional neuroradiological procedures. Chest X-ray and CT Pulmonary Angiogram images are shown. The case highlights the importance of a thorough clinical history, including past medical history, when interpreting radiological studies.

Pipeline Flex embolisation device with Shield Technology for the treatment of patients with intracranial aneurysms: periprocedural and 6 month outcomes.

BACKGROUND AND PURPOSE: The Pipeline Flex embolisation device with Shield Technology (Pipeline Shield) is a novel flow diverter which reduces intra-vessel thrombogenicity. This study summarises periprocedural outcomes and 6-month follow-up results following its introduction in a tertiary interventional neuroradiology centre. MATERIALS AND METHODS: This prospective, single-arm study assessed 32 aneurysms treated over a 21-month time period from the time of procedure to 6 months post-procedure. Data collected included patient demographics, aneurysm features and intraprocedural and 6-month post-procedural complications. RESULTS: The mean age of the cohort was 58.8 ± Standard Deviation 8.5 years. Twenty-eight aneurysms were treated electively and four acutely. The elective cases received dual antiplatelet therapy post-procedure. The acute cases received single antiplatelet therapy post-procedure. Of the target aneurysms, 16/32 (50%) were small (<10 mm), 13/32 (41%) were large (10-25 mm) and 3/32 (9%) were giant (≥25 mm). There was no mortality in the series. There were two periprocedural complications (2/32, 6.2%): a stroke and a dissection. There were no post-procedural complications. At 6 months post-procedure, satisfactory occlusion (defined as Raymond-Roy 1 or 2) was achieved in 90.6% and 93.8% by way of magnetic resonance angiography and digital subtraction angiography assessment, respectively. There was no implant migration, no significant intraluminal hyperplasia or in-stent stenosis and no cases of aneurysm recurrence. CONCLUSION: The Pipeline Shield has an excellent 6- month safety profile with an acceptable rate of intraprocedural complications, no post-procedure complications and no mortality in this case series of 32 acute and elective cases.

Animated stories of medical error as a means of teaching undergraduates patient safety: an evaluation study.

BACKGROUND: Storytelling is a powerful form of communication which can improve attention and lead to lasting behavioural changes. Addressing the need to incorporate patient safety teaching into undergraduate medical curricula, it was hypothesized that medical students could benefit from hearing clinician stories of medical error. The medium of animation was considered to be a potentially engaging means of presenting stories of error to a large audience. METHODS: Three animated videos were developed to accompany audio recordings of junior doctors describing their experiences of a serious incident or near-miss event. The videos were delivered to 200 final-year medical students with a subsequent large-group discussion directed at understanding contributory factors. An evaluative questionnaire exploring learners' reactions and modification of beliefs and perception was distributed. The questionnaire included questions rated on a modified Likert scale and a free-text box. A mixed-methods analysis was conducted with descriptive statistics and qualitative content analysis of the free-text responses. RESULTS: Of the 200 students who attended, 104 completed the questionnaire and 83 completed free-text feedback. Most students responded positively to hearing stories of medical error and felt that the animated videos improved their engagement while the voice recordings helped bring the cases to life. The majority of students agreed the session would impact on their future practice. CONCLUSION: This pilot study confirmed that undergraduate students consider animated, personal stories of medical error an effective, engaging means of learning about patient safety. Longitudinal studies are required to confirm if measurable behaviour change is achieved.

Macrophage-mediated response to hypoxia in disease.

Hypoxia plays a critical role in the pathobiology of various inflamed, diseased tissues, including malignant tumors, atherosclerotic plaques, myocardial infarcts, the synovia of rheumatoid arthritic joints, healing wounds, and sites of bacterial infection. These areas of hypoxia form when the blood supply is occluded and/or the oxygen supply is unable to keep pace with cell growth and/or infiltration of inflammatory cells. Macrophages are ubiquitous in all tissues of the body and exhibit great plasticity, allowing them to perform divergent functions, including, among others, patrolling tissue, combating invading pathogens and tumor cells, orchestrating wound healing, and restoring homeostasis after an inflammatory response. The number of tissue macrophages increases markedly with the onset and progression of many pathological states, with many macrophages accumulating in avascular and necrotic areas, where they are exposed to hypoxia. Recent studies show that these highly versatile cells then respond rapidly to the hypoxia present by altering their expression of a wide array of genes. Here we review the evidence for hypoxia-driven macrophage inflammatory responses in various disease states, and how this influences disease progression and treatment.