Background: Bariatric surgery patients are at a higher risk for venous thrombotic events. Inferior vena cava filter (IVCf) placement to prevent thrombotic complications is still considered controversial in bariatric surgery patients, especially when left in place long term. In this study, we describe our experience with the use of retrievable IVCf and their safety in bariatric surgery patients. Methods: A retrospective chart review was performed in a single bariatric surgery center. Patients with a body mass index (BMI) greater than 50, with a history of thromboembolic events, hypercoagulable conditions, and low mobility were defined as high risk and underwent exclusively retrievable IVCf placement. All also received preoperative heparin and postoperative low-molecular weight heparin prophylaxis. All patients underwent venogram during the filter retrieval. Results: Forty-nine patients, 36 females and 13 males, were reviewed. Mean age was 48, mean BMI was 53.7. Thirty-five patients underwent laparoscopic gastric bypass, 8 laparoscopic gastric banding, and 5 laparoscopic sleeve gastrectomy. 54.1% of patients received retrievable inferior vena cava filter (rIVCF) for a BMI >50 (n = 26); 27.2% for a personal history of deep venous thrombosis (DVT)/pulmonary embolism (PE) (n = 13); 6.2% for a family history of DVT/PE (n = 3); 8.3% for known hyper coagulable state without prior DVT/PE (n = 4); and 4.2% for low mobility or immobility (n = 2). Forty-eight patients out of 49 successfully received rIVCF. 98% of filters (47 out of 48) were removed successfully without any complications. One patient did not return to follow-up. One patient developed nonfatal DVT and PE, while the filter was still in place. There were no complications from filter placement or removal. Conclusions: The use of retrievable IVC filters for the prophylaxis of venous thromboembolism in bariatric surgery in conjunction with chemoprophylaxis therapy is safe and effective.

We report an unusual case of gastric conduit ischemia as a result of celiac artery stenosis presenting 24 years after esophagectomy.

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.

Previous work has demonstrated that poly (ADP-ribose) polymerase (PARP) inhibition confers protection on skeletal muscle ischemia–reperfusion (IR) injury in diabetic mice. Published reports, including a model of renal IR injury in normal nondiabetic mice, have shown that poly (ADP-ribosylation) of the critical glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH) results in reduced enzyme activity, thereby reducing energy metabolites. This study aims to determine whether PARP inhibition modulates the activity and level of poly (ADP-ribosylation) of GAPDH, along with energy substrates within diabetic skeletal muscle after IR.

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.

The interaction between neuropeptides and cytokines and its role in cutaneous wound healing is becoming evident. The goal of the present study is to investigate the impact of diabetes on peripheral cytokine and neuropeptide expression and its role in diabetic wound healing. To achieve this goal, the effect of diabetes on wound healing, along with the role of inflammatory cytokines such as interleukin-6 (IL-6) and interleukin-8 (IL-8) secreted in the wound microenvironment, and neuropeptides such as substance P (SP) and neuropeptide Y (NPY), secreted from peripheral nerves is monitored in non-diabetic and diabetic rabbits.Rabbits in the diabetic group received alloxan monohydrate (100mg/kg i.v.). Ten days after diabetic induction, four full thickness circular wounds were created in both ears using a 6mm punch biopsy. Wound healing was monitored over 10 d and gene expression of cytokines and neuropeptides was assessed in the wounds.Compared with the non-diabetic rabbits, wounds of diabetic rabbits heal significantly slower. Diabetic rabbits show significantly increased baseline gene expression of IL-6 and IL-8, their receptors, CXCR1, CXCR2, GP-130, and a decrease of prepro tachykinin-A (PP-TA), the precursor of SP, whereas the expression of prepro-NPY (PP-NPY), the precursor of NPY is not different. Similarly, baseline protein expression of CXCR1 is higher in diabetic rabbit skin. Post-injury, the increase over baseline gene expression of IL-6, IL-8, CXCR1, CXCR2, and GP-130 is significantly less in diabetic wounds compared with non-diabetic wounds. Although there is no difference in PP-TA gene expression between non-diabetic and diabetic rabbits post-injury, the gene expression of PP-NPY is reduced in diabetic rabbits.In conclusion, diabetes causes dysregulation in the neuropeptide expression in the skin along with a suppressed focused inflammatory response to injury. This suggests that the chronic inflammation in the skin of diabetic rabbits inhibits the acute inflammation much needed for wound healing. (C) 2011 Elsevier Inc. All rights reserved.

As the use of retrievable filters increases, the need for widely adaptable techniques to remove embedded IVC filters will increase. The use of the rigid bronchoscopy forceps allows embedded filters to be removed safely in patients who would otherwise have a tilted filter left in place permanently. However the rigid straight shaft may prevent the operator from successfully directing the forceps and grasping the tip of the filter. We describe the first intravascular use of a steerable laparoscopic grasping forcep to remove an embedded IVC filter. A 58-yo patient was referred 1 yr after undergoing catheter directed thrombolysis and placement of a retrievable IVC filter for treatment of DVT/PE. She had undergone an unsuccessful attempt at filter retrieval via an Internal Jugular (IJ) approach. CT scan revealed that the tip of the Bard Filter was embedded in the anterior wall of the IVC (Fig 1). A second unsuccessful attempt at retrieving the filter via an isolated RIJ approach was performed using snares, retrieval cones and biopsy forceps. The patient was returned to the endovascular suite 1 month later for another attempt using a combined RIJ and Femoral venous approach. The Bard retrieval cone was introduced via a 12 fr sheath in the RIJ. A novel laparoscopic fenestrated alligator grasper with a steerable tip with 90 degrees deflection and 360 degrees rotation was introduced via an 18 fr sheath in femoral vein. The grasper was used to remove the tip of the filter from the IVC wall and redirect it into the lumen where it was captured using the retrieval cone (Fig 2).Fig 2View Large Image Figure ViewerDownload Hi-res image Download (PPT) Completion IVC gram demonstrated no thrombus, or extravasation of contrast. Repeat CT scan at 6 weeks revealed a widely patent IVC with no thrombus. A steerable laparoscopic grabber may facilitate the retrieval of embedded/tipped IVC filters. It may also have use for the retrieval of other foreign bodies within the vascular system.

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. ( J Vase Surg 2010;52:1608-15.)

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.

Huang, Zhen Shao MD; Malek, Junaid Y. MD; Bhasin, Manoj K. MA, PhD; Contreras, Mauricio A. MD; LoGerfo, Frank W. MD, FACS Author Information

Our study employed laser capture microdissection to selectively collect endothelial (EC) and smooth muscle cells (SMC) from patent canine femoral artery bypass cephalic vein grafts (n=3) and normal contralateral cephalic vein controls (harvested after 24 hours). Total RNA was purified, converted to cDNA, and prepared for Affymetrix Canine 2.0 GeneChip hybridization (43,036 probes, 16,984 genes). Sample purities were measured via qRT‐PCR (EC: CD31, eNOS, vWF; SMC: α‐actin 2, SMC‐MHCII). Chip normalization and analysis were executed with BioConductor and dChip. Significantly up‐ (UR) or downregulated (DR) graft genes had =2.0 fold change versus control and absolute lower confidence bound of =2.0. Human genes were matched using BLAST PERL. Average isolate purities were 43‐78% for EC and 79‐100% for SMC. In grafts versus controls, 2101 genes were differentially expressed in EC and 1753 in SMC. UR genes: 1112 in EC, 729 in SMC, 322 in common. DR genes: 989 in EC, 1024 in SMC, 444 in common. Clustering analysis showed unique clustering of graft versus control EC and SMC. Gene ontology analysis exhibited predominant gene functions in protein binding (EC & SMC), cellular processes involved in inflammation (EC) and cell motility (SMC) and localizations to the plasma membrane (EC) and ECM (SMC). LCM is effective in separating gene responses in the intima from the media of vein grafts. NIH 5 T32 HL007734 & 5 R01 HL086741 to FWL

Malek, Junaid Y. MD; Andersen, Nicholas D. MD; Martin, Michelle C. MD; Monahan, Thomas S. MD; Contreras, Mauricio A.; Ferran, Christiane MD, PhD; Pradhan, Leena PhD; LoGerfo, Frank W. MD, FACS Author Information

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.