Room for improvement in patient compliance during peripheral vascular interventions.

Introduction: For patients receiving Procedural Sedation and Analgesia (PSA), patient cooperation is crucial as patients remain continuously aware of operating room activity and can be asked to perform tasks such as prolonged breath-holds. This survey aimed to collect information on patient compliance with on-table instructions and its relation to periprocedural outcomes from surgeons nationwide performing peripheral vascular interventions (PVI) under PSA. Methods: A 9-question online survey was sent to 383 vascular surgeons (including both vascular surgery attendings and trainees) across the United States through REDCap from August 30 to September 21, 2021, with responses closed on October 30, 2021. The survey response was analyzed with descriptive statistics. Results: 83 (21.6%) vascular surgeons responded to the survey, of which 67 (80.7%) were attending vascular surgeons and 16 (19.3%) were vascular surgery trainees. 41 (49.4%) respondents performed 11-20 PVI cases under PSA every month, while 31 (41.0%) respondents performed 1-10 PVI cases under PSA every month. 41 (49.4%) respondents reported that in 1-10% of their cases, additional contrast and/or radiation was administered because patient moved on the table or did not cooperate with breath holds; 25 (30.1%) reported that this occurred in 11-20% of their cases, 12 (14.5%) reported that this occurred in 21-50% of their cases and 4 (4.8%) reported that this occurred in over 50% of their cases. In such cases, the majority of respondents reported a 1-10% increase in contrast volume (59.0%), radiation dosage (62.7%), sedative/analgesia administration (46.3%) and procedural time (54.9%). Of cases being converted to general anesthesia due to inadequate patient cooperation, 35 (42.2%) respondents reported between 1-5 per month, and 3 (3.6%) respondents reported between 6-10 per month. Of cases being aborted due to inadequate patient cooperation, 25 (30.1%) respondents reported between 1-5 per month, and 1 (1.2%) respondents reported between 6-10 per month. Conclusion: A significant fraction of PVI cases performed under PSA result in increased radiation and contrast exposure, sedative administration and procedural time due to inadequate patient cooperation. In certain cases, conversion to general anesthesia or case abortion is required. Further research should be performed to investigate strategies to minimize such adverse patient safety events.

Presentation and treatment outcomes of patients with symptomatic inferior vena cava filters.

BACKGROUND: Use of inferior vena cava filters (IVCFs) has become more prevalent for the prevention of venous thromboembolism in part due to their ease of deployment and retrieval. Nonthrombotic complications of IVCFs are unusual but have been described. This study characterizes this cohort of patients and elucidates their clinical outcome. METHODS: Between January 1, 2006 and December 31, 2011, six patients were identified with nonthrombotic symptoms attributed to their IVCF. Symptoms included abdominal/back pain, hypertension from renal artery compression, and hydroureter from ureteral compression. RESULTS: The average age of the patients was 38.8 years (range 21 to 71 years) and all were female. Indication for IVCF placement included deep vein thrombosis (n = 2), deep vein thrombosis with pulmonary embolism (n = 1), and perioperative prophylaxis (n = 3). Filter types included the Ninitol Bard G2 (n = 3), Cook Celect (n = 1), Gunther Tulip (n = 1), and ALN (n = 1). The median time from IVCF placement to retrieval was 285 days (range 20 to 2091 days). At presentation, all IVCFs were tilted and had struts penetrating through the vena cava wall. Every IVCF was successfully removed: four by endovascular approach and two by open surgery. All patients had complete resolution of symptoms and there were no procedural complications. CONCLUSIONS: Symptomatic IVCFs occur in female patients, and are always associated with device strut erosion outside the inferior vena cava. Successful retrieval can be safely achieved by an endovascular or open surgical technique, resulting in symptom resolution.

Temporal network based analysis of cell specific vein graft transcriptome defines key pathways and hub genes in implantation injury.

Vein graft failure occurs between 1 and 6 months after implantation due to obstructive intimal hyperplasia, related in part to implantation injury. The cell-specific and temporal response of the transcriptome to vein graft implantation injury was determined by transcriptional profiling of laser capture microdissected endothelial cells (EC) and medial smooth muscle cells (SMC) from canine vein grafts, 2 hours (H) to 30 days (D) following surgery. Our results demonstrate a robust genomic response beginning at 2 H, peaking at 12-24 H, declining by 7 D, and resolving by 30 D. Gene ontology and pathway analyses of differentially expressed genes indicated that implantation injury affects inflammatory and immune responses, apoptosis, mitosis, and extracellular matrix reorganization in both cell types. Through backpropagation an integrated network was built, starting with genes differentially expressed at 30 D, followed by adding upstream interactive genes from each prior time-point. This identified significant enrichment of IL-6, IL-8, NF-κB, dendritic cell maturation, glucocorticoid receptor, and Triggering Receptor Expressed on Myeloid Cells (TREM-1) signaling, as well as PPARα activation pathways in graft EC and SMC. Interactive network-based analyses identified IL-6, IL-8, IL-1α, and Insulin Receptor (INSR) as focus hub genes within these pathways. Real-time PCR was used for the validation of two of these genes: IL-6 and IL-8, in addition to Collagen 11A1 (COL11A1), a cornerstone of the backpropagation. In conclusion, these results establish causality relationships clarifying the pathogenesis of vein graft implantation injury, and identifying novel targets for its prevention.

Endothelial cells are susceptible to rapid siRNA transfection and gene silencing ex vivo.

BACKGROUND: Endothelial gene silencing via small interfering RNA (siRNA) transfection represents a promising strategy for the control of vascular disease. Here, we demonstrate endothelial gene silencing in human saphenous vein using three rapid siRNA transfection techniques amenable for use in the operating room. METHODS: Control siRNA, Cy5 siRNA, or siRNA targeting glyceraldehyde-3-phosphate dehydrogenase (GAPDH) or endothelial specific nitric oxide synthase (eNOS) were applied to surplus human saphenous vein for 10 minutes by (i) soaking, (ii) applying 300 mm Hg hyperbaric pressure, or (iii) 120 mm Hg luminal distending pressure. Transfected vein segments were maintained in organ culture. siRNA delivery and gene silencing were assessed by tissue layer using confocal microscopy and immunohistochemistry. RESULTS: Distending pressure transfection yielded the highest levels of endothelial siRNA delivery (22% pixels fluorescing) and gene silencing (60% GAPDH knockdown, 55% eNOS knockdown) as compared with hyperbaric (12% pixels fluorescing, 36% GAPDH knockdown, 30% eNOS knockdown) or non-pressurized transfections (10% pixels fluorescing, 30% GAPDH knockdown, 25% eNOS knockdown). Cumulative endothelial siRNA delivery (16% pixels fluorescing) and gene silencing (46% GAPDH knockdown) exceeded levels achieved in the media/adventitia (8% pixels fluorescing, 24% GAPDH knockdown) across all transfection methods. CONCLUSION: Endothelial gene silencing is possible within the time frame and conditions of surgical application without the use of transfection reagents. The high sensitivity of endothelial cells to siRNA transfection marks the endothelium as a promising target of gene therapy in vascular disease.

Endoluminal intervention for limb salvage after failed lower extremity bypass graft.

BACKGROUND: Lower extremity bypass graft failure in patients with limb-threatening ischemia carries an amputation rate of greater than 50%. Redo bypass is often difficult due to the lack of conduit, adequate target, or increased surgical risk, and resultant limb salvage rates are reduced significantly compared with the index operation. We set forth to investigate whether endovascular treatment in this setting would result in an acceptable limb salvage rate. METHODS: A single-institution, retrospective review from June 2004 to December 2007 of patients with failed grafts who underwent endovascular treatment with percutaneous balloon angioplasty (PTA) of their native circulation was performed. Stents were selectively used in cases of post-PTA residual stenosis or flow-limiting dissection. Technical success was defined as a residual stenosis less than 30%. Percutaneous attempts at bypass graft salvage were excluded. Demographics, comorbidities, procedural data, and follow-up information were recorded. Descriptive, logistic regression and life-table analyses were performed. RESULTS: Twenty-four lower extremities were treated in 23 patients with failed bypass grafts. Average patency of the index graft before failure was 647 days (range 5-2758). Mean age was 68 years (range 51-85), 62% were male and 81% had diabetes mellitus (DM). 87.5% of limbs treated had TransAtlantic InterSociety Consensus (TASC) C and D lesions and 62% had multiple lesions. Technical success was achieved in 100%. Mean follow-up was 25.6 months. At follow-up, there were 17 PTA failures, which resulted in: amputation (4), redo-bypass (3), and redo-PTA (11). Freedom from surgical revision and PTA failure was 89% (+/- 0.07 SE) and 28% (+/- 0.09 SE) respectively. PTA secondary patency was 72% (+/- 0.09 SE) and limb-salvage was 81% (+/- 0.08 SE) at both 12 and 24 months. Overall survival was 83% (+/- 0.07 SE) and 77% (+/- 0.09 SE) at 12 and 24 months, respectively. CONCLUSIONS: Endovascular treatment of patients with previously failed bypass grafts results in a high rate of limb salvage. This is a reasonable option in selected patients and the primary choice in those with poor targets, conduit, or excess surgical risk. Endovascular salvage should be considered before proceeding to primary amputation.

MARCKS silencing differentially affects human vascular smooth muscle and endothelial cell phenotypes to inhibit neointimal hyperplasia in saphenous vein.

Intimal hyperplasia (IH) limits the patency of all cardiovascular vein bypass grafts. We previously found the myristoylated alanine-rich C kinase substrate (MARCKS), a key protein kinase C (PKC) substrate, to be up-regulated in canine models of IH. Here, we further characterize the role of MARCKS in IH and examine the phenotypic consequences of MARCKS silencing by small interfering RNA (siRNA) transfection in human vascular smooth muscle cells (VSMCs) and endothelial cells (ECs) in vitro and use a rapid 10-min nonviral siRNA transfection technique to determine the effects of MARCKS silencing in human saphenous vein cultured ex vivo. We demonstrate MARCKS silencing attenuates VSMC migration and arrests VSMC proliferation in part through the up-regulation of the cyclin-dependent kinase inhibitor p27(kip1). Conversely, MARCKS silencing had little or no effect on EC migration or proliferation. These phenotypic changes culminated in reduced neointimal formation in cultured human saphenous vein. These data identify MARCKS as a pathogenic contributor to IH and indicate therapeutic MARCKS silencing could selectively suppress the "atherogenic," proliferative phenotype of VSMCs without collateral harm to the endothelium. This approach could be readily translated to the clinic to silence MARCKS in vein bypass grafts prior to implantation.

Combined microsurgical and endovascular management of complex intracranial aneurysms.

OBJECTIVE: The disciplines of microneurosurgery and cranial base surgery have reached maturity, and technical advances in the surgical management of aneurysms are limited. Although most aneurysms can be clipped microsurgically or coiled endovascularly, a subset of patients may require a combined approach. A consecutive series of patients with aneurysms in one surgeon's cerebrovascular practice was reviewed retrospectively to analyze strategies for integrating microsurgical and endovascular techniques in the management of complex aneurysms. METHODS: Between 1997 and 2001, 596 aneurysms in 491 patients were treated microsurgically by the senior author (MTL) at the University of California, San Francisco, and 77 of these patients (96 aneurysms) were managed with a multimodality approach comprising a total of eight different combinations: selective revascularization and aneurysm occlusion (n = 23), endovascular and surgical trapping (n = 1), clipping of the aneurysm after attempted or incomplete coiling (n = 22), coiling after attempted or incomplete clipping (n = 5), clipping of recurrent aneurysm after coiling (n = 6), coiling of recurrent aneurysm after clipping (n = 1), clipping and coiling of multiple remote aneurysms (n = 13), and coiling after previous surgery (n = 6). RESULTS: A total of 96 aneurysms were treated with combined therapy, of which 43% were large or giant in size and 34% had fusiform or dolichoectatic morphology. Complete angiographic obliteration was achieved in 91 aneurysms (95%). Overall, 66 patients (86%) had good outcomes (Glasgow Outcome Scale score of 4 or 5; mean follow-up, 9 mo). The treatment mortality rate was 9.1% (seven patients), and permanent treatment-associated neurological morbidity rate was 5.2% (four patients). CONCLUSION: Evolving endovascular technologies need to be integrated into the microsurgical management of aneurysms. Multimodality approaches are best used with complex aneurysms in which conventional therapy with a single modality has failed. Revascularization remains a unique surgical contribution to the overall management of aneurysms with which current endovascular techniques cannot be used. Multimodality management should be considered an elegant addition to the therapeutic armamentarium that, through simplification and increased safety, improves the treatment of complex aneurysms beyond what is achievable by performing clipping or coiling alone.

Comparison of gene silencing in human vascular cells using small interfering RNAs.

BACKGROUND: Gene silencing achieved through small interfering RNA (siRNA) transfection represents a promising approach to vascular gene therapy. Here we characterize the behavior of RNA interference (RNAi) in vascular biology by comparing the RNAi response to single- and multigene siRNA transfections in vitro in human vascular cells. STUDY DESIGN: The strength and specificity of multigene silencing in cultured human coronary artery smooth muscle and human coronary artery endothelial cells (HCASMC/HCAEC) were assessed by quantitative reverse transcription-polymerase chain reaction (QRT-PCR) and Western blot after transfection singly or simultaneously with siRNAs targeting glyceraldehyde-3-phosphate dehydrogenase, the myristoylated alanine-rich C kinase substrate, and cadherin 11. RNAi response to low-dose (0.25 to 10 nM) siRNA transfection was characterized between the two cell types by QRT-PCR and fluorescence-activated cell sorter analysis. RESULTS: Powerful and specific silencing of all targets was observed in both cell types after multigene siRNA transfections, but with a reduction in effect compared with single-gene siRNA transfections. Multigene messenger RNA (mRNA) reductions in HCAECs exceeded those achieved in HCASMCs, and superior mRNA silencing and siRNA delivery were observed in HCAECs after low-dose siRNA transfections. CONCLUSIONS: Multigene silencing by siRNA stands as a promising nonviral approach for manipulating gene expression in human vascular cells. Under our in vitro conditions, endothelial cells were more susceptible to siRNA transfection and gene silencing than vascular smooth muscle cells. RNAi technology could potentially find use in the development of siRNA cocktails for application to vein bypass grafts or for modulating endothelial cell function in other forms of vascular disease.

Metabolic effects of hypothermia and its neuroprotective effects on the recovery of metabolic and electrophysiological function in the ischemic retina in vitro.

OBJECTIVE: Reduction in energy usage has been investigated as the mechanism by which hypothermia provides protection during ischemia. We describe experiments using hypothermia in the rabbit retina in vitro that show a correlation between hypothermia-induced reductions in energy usage and neuroprotection. METHODS: We examined energy metabolism and electrophysiological function under control/nonischemic conditions during 1 or 2 hours of "ischemia" (induced by decreasing glucose from 6 to 1 mmol/L and oxygen from 95 to 15%) and during 3 to 4 hours of "return-to-control" conditions. Glucose utilization and lactate production were measured as indices of energy metabolism, and light-evoked compound action potentials were monitored to assess functional recovery. RESULTS: Nonischemic retinas subjected to both mild (33 +/- 0.5 degrees C) and moderate (30 +/- 0.5 degrees C) hypothermia exhibited a decrease of 38% in the rate of glucose utilization and lactate production compared with normothermic retinas (36 +/- 0.5 degrees C) (analysis of variance, P < 0.001). In retinas that were made ischemic, mild or moderate hypothermia further reduced the rates of glucose utilization (18 and 39%, respectively) and lactate production (21 and 28%, respectively) (P < 0.001 for glucose, P < 0.01 for lactate). Retinas that had been mildly or moderately hypothermic during ischemia exhibited improved recovery of glucose utilization (65 and 57%, respectively) and lactate production (72 and 74%, respectively) compared with normothermic retinas (18% for glucose and 54% for lactate; repeated-measures analysis of variance, P < 0.001). Recovery of compound action potentials for retinas kept at 36, 33, and 30 degrees C was 15, 36, and 53%, respectively (repeated-measures analysis of variance, P < 0.001). CONCLUSION: Our studies in an avascular neuronal model of ischemia demonstrate that hypothermia protects against ischemic injury. We interpret the smaller reductions in energy generation and usage caused by ischemia when the retinas were hypothermic as evidence that hypothermia had reduced energy requirements more than energy production, and we propose that this at least in part explains its protection.

Combined microsurgical and endovascular management of complex intracranial aneurysms.

OBJECTIVE: The disciplines of microneurosurgery and cranial base surgery have reached maturity, and technical advances in the surgical management of aneurysms are limited. Although most aneurysms can be clipped microsurgically or coiled endovascularly, a subset of patients may require a combined approach. A consecutive series of patients with aneurysms in one surgeon's cerebrovascular practice was reviewed retrospectively to analyze strategies for integrating microsurgical and endovascular techniques in the management of complex aneurysms. METHODS: Between 1997 and 2001, 596 aneurysms in 491 patients were treated microsurgically by the senior author (MTL) at the University of California, San Francisco, and 77 of these patients (96 aneurysms) were managed with a multimodality approach comprising a total of eight different combinations: selective revascularization and aneurysm occlusion (n = 23), endovascular and surgical trapping (n = 1), clipping of the aneurysm after attempted or incomplete coiling (n = 22), coiling after attempted or incomplete clipping (n = 5), clipping of recurrent aneurysm after coiling (n = 6), coiling of recurrent aneurysm after clipping (n = 1), clipping and coiling of multiple remote aneurysms (n = 13), and coiling after previous surgery (n = 6). RESULTS: A total of 96 aneurysms were treated with combined therapy, of which 43% were large or giant in size and 34% had fusiform or dolichoectatic morphology. Complete angiographic obliteration was achieved in 91 aneurysms (95%). Overall, 66 patients (86%) had good outcomes (Glasgow Outcome Scale score of 4 or 5; mean follow-up, 9 mo). The treatment mortality rate was 9.1% (seven patients), and permanent treatment-associated neurological morbidity rate was 5.2% (four patients). CONCLUSION: Evolving endovascular technologies need to be integrated into the microsurgical management of aneurysms. Multimodality approaches are best used with complex aneurysms in which conventional therapy with a single modality has failed. Revascularization remains a unique surgical contribution to the overall management of aneurysms with which current endovascular techniques cannot be used. Multimodality management should be considered an elegant addition to the therapeutic armamentarium that, through simplification and increased safety, improves the treatment of complex aneurysms beyond what is achievable by performing clipping or coiling alone.