The management of diabetic foot: a clinical practice guideline by the Society for Vascular Surgery in collaboration with the American Podiatric Medical Association and the Society for Vascular Medicine

Diabetes mellitus continues to grow in global prevalence and to consume an increasing amount of health care resources. One of the key areas of morbidity associated with diabetes is the diabetic foot. To improve the care of patients with diabetic foot and to provide an evidence-based multidisciplinary management approach, the Society for Vascular Surgery in collaboration with the American Podiatric Medical Association and the Society for Vascular Medicine developed this clinical practice guideline.

Safety and efficacy of plasmid DNA expressing two isoforms of hepatocyte growth factor in patients with critical limb ischemia.

VM202, a plasmid DNA that expresses two isoforms of hepatocyte growth factor, may elicit angiogenic effects that could benefit patients with critical limb ischemia (CLI). In a phase 2, double-blind trial in 52 CLI patients, we examined the safety and potential efficacy of intramuscular injections of low-dose (n=21) or high-dose (n=20) VM202 or placebo (n=11) in the affected limb (days 0, 14, 28 and 42). Adverse events and serious adverse events were similar among the groups; no malignancy or proliferative retinopathy was seen. In exploratory efficacy analyses, we found no differences in ankle or toe-brachial index, VAS, VascuQuol or amputation rate among the groups. Complete ulcer healing was significantly better in high-dose (8/13 ulcers; P<0.01) versus placebo (1/9) patients. Clinically meaningful reductions (>50%) in ulcer area occurred in high-dose (9/13 ulcers) and low-dose (19/27) groups versus placebo (1/9; P<0.05 and P<0.005, respectively). At 12 months, significant differences were seen in TcPO2 between the high-dose and placebo groups (47.5 ± 17.8 versus 36.6 ± 24.0 mm Hg, respectively; P<0.05) and in the change from baseline among the groups (P<0.05). These data suggest that VM202 is safe and may provide therapeutic bioactivity in CLI patients.

Total contact casting combined with human fibroblast-derived dermal tissue in 15 DFU patients.

OBJECTIVE: To investigate the use of a cryopreserved human fibroblast-derived dermal substitute (Dermagraft; DG) in combination with total contact casting (TCC) in patients with diabetic foot ulcers, compared with previously published rates of healing with TCC alone. METHOD: Fifteen consecutive diabetic foot ulcer patients were referred to a multi-speciality clinic to be managed with a combination of DG and TCC, after showing no progress toward healing following at least 4 weeks of standard, conservative therapy. Follow-up visits were scheduled every 7 days, for a period of 12 weeks, or until fully healed. At each visit, DG and TCC were applied by the investigating clinician, and ulcer size and depth were recorded. Photographs were taken once a month, or when healed. If indicated, debridement was done to remove fibrotic tissue, callus and slough. RESULTS: The results demonstrated an average healing rate of 23.7 ± 16.3 days. The average number of DG applications was 2.1. There was no correlation observed between ulcer duration, or ulcer location (forefoot or mid-foot), and time to healing; however, a correlation was found between wound size and healing time. CONCLUSION: The findings may suggest combining advanced healing modalities, such as DG with TCC, can be done and that they may have a benefit of limiting the time spent in TCC, as well as a reduction in time to heal. The study size was small and further studies into combining modalities are warranted to validate these findings. DECLARATION OF INTEREST: Both authors have been paid consultants for Advanced Biohealing, the producers of Dermagraft (DG). There are no financial disclosures for Med Efficiency, Inc. (MedE-Kast Ultra; TCC), or any other conflicts of interest to declare.

Powered phlebectomy (TriVex) in treatment of varicose veins.

This study assesses the operation of transilluminated powered phlebectomy for removal of varicose veins. It was a prospective, noncomparative, multicenter, pilot study designed to evaluate the safety and efficacy of the powered varicose vein extractor for ablation of primary varicose veins. A total of 114 patients (117 limbs) were recruited from four centers in Europe and four centers in the United States. Safety of the varicose vein extractor was evaluated by recording nature and severity of all adverse events and complications. Efficacy was assessed by the patient, an independent study nurse, and the surgeon. Operations were performed under general, spinal, or epidural anesthesia and tumescent anesthesia was added with infusions of dilute lidocaine with epinephrine. Transillumination was achieved with a specially designed cannula, and the vein extraction was done using a vein resector with a rotating tubular inner cannula encased in a stationary outer sheath dissector. Demographic information regarding the 28 men and 89 women included in the study are detailed. Eighty-four percent of the limbs were CEAP class 2 with only 16% being in classes 3 and 4. Accompanying greater saphenous vein stripping was done in 67% of the limbs in the United States and 88% in those in Europe. Proximal ligation only was used in one limb in the United States and eight in Europe. The study showed that transilluminated powered phlebectomy used in varicose vein removal is swift and efficacious with a conservation of operating time and the results being satisfactory to the patient and clinician alike.

Differential expression of the mismatch repair gene hMSH2 in malignant prostate tissue is associated with cancer recurrence.

BACKGROUND: Mismatch repair (MMR) genes are responsible for coordinated correction of misincorporated nucleotides formed during DNA replication. Inactivating mutations in MMR genes have been described in sporadic cancers and a hereditary cancer predisposition syndrome. Mismatch repair deficiency causes instability at microsatellites and increased mutation rates. Although microsatellite instability (MSI) has been described in high-grade and lymph node positive prostate carcinoma specimens, an analysis comparing hMSH2 expression, MSI, and outcome in clinically organ confined prostate carcinoma has not been reported. METHODS: Immunohistochemical analysis of benign and malignant prostate tissue from 101 patients was performed using a monoclonal antibody specific for the hMSH2 protein. Expression was correlated with MSI using dinucleotide repeat markers and laser-captured microdissected DNA from normal and tumor cells. hMSH2 protein expression and MSI were assessed with respect to pathologic stage, Gleason score, and time to detectable serum prostate specific antigen (PSA) after prostatectomy in patients with clinically localized prostate carcinoma. RESULTS: In normal glands, hMSH2 staining was minimal to low and confined to the basal cell layer. In 32% of benign prostatic hyperplasia cases, hMSH2 staining was increased in the basal and luminal cell layers whereas 71% of cancer specimens had uniform moderate to high staining. Microsatellite instability was detected in 60% of absent to low staining and 26% of moderate to high staining prostate carcinoma specimens. Differential staining in benign versus malignant prostate tissues was statistically significant (P < 0.001) as was the correlation between absent to low hMSH2 staining and presence of MSI (P = 0.028). Decreased risk for PSA recurrence after radical prostatectomy correlated with absent to low hMSH2 staining in malignant prostate tissue but was only marginally significant (P = 0.05 for 24 month recurrence and P = 0.08 for overall time to PSA recurrence). CONCLUSIONS: The results of the current study demonstrate differential hMSH2 expression in benign and malignant prostate tissue. Moreover, hMSH2 expression is altered in a subset of clinically localized prostate carcinoma specimens independent of pathologic stage and Gleason pattern. A statistically significant correlation between hMSH2 immunohistochemical staining intensity and MSI also was identified in prostate carcinoma specimens. Furthermore, the time to cancer recurrence as determined by detectable serum PSA after prostatectomy was associated with hMSH2 staining intensity. Taken together, our results suggest that hMSH2 gene expression in prostate carcinoma may be a useful prognostic marker for outcome in men with clinically organ confined prostate carcinoma.

Complications of lumbar drainage after thoracoabdominal aortic aneurysm repair.

OBJECTIVES: Paraplegia remains a frequent complication of thoracoabdominal aortic aneurysm (TAAA) repair. Many adjunct therapies have been developed to address this complication. Lumbar drainage is frequently used in an attempt to decrease intrathecal pressure and improve intramedullary perfusion pressure. The effectiveness of this therapy is unclear, and the complications of lumbar drainage used for this indication are unknown. We present a case of intraspinal hematoma with significant neurologic deficit after TAAA repair and review the associated complications of lumbar drains placed for TAAA. METHODS: The charts of all patients undergoing operations for TAAA repair were reviewed. Patients who underwent perioperative placement of a lumbar drain were included regardless of aneurysm type or etiology. Demographics, Crawford grade, and perioperative parameters and complications were reviewed. RESULTS: Sixty-five patients underwent TAAA repair with 62 (95%) receiving a preoperative lumbar drain. There were two (3.2%) intraspinal hemorrhagic complications, including one patient with a poor neurologic outcome. No infections or other complications directly related to drainage were identified. Multivariate logistic regression analysis failed to demonstrate a significant association between lumbar drain complications and perioperative and intraoperative parameters such as blood loss or hypotension, level of drain placement, and Crawford grade. CONCLUSIONS: Lumbar drainage is a frequent adjunct to TAAA repair. However, placement of the drain itself can be associated with significant complications whose aggravating factors may be unidentifiable. Complications resulting from lumbar drainage should be considered in any patient who has postoperative lower extremity neurologic deficits.

Overexpression of the focal adhesion kinase (p125FAK) in the vascular smooth muscle cells of intimal hyperplasia.

PURPOSE: The migration and proliferation of vascular smooth muscle cells (VSMCs) are important events in the development of intimal hyperplasia (IH). The focal adhesion kinase (FAK) gene encodes a protein tyrosine kinase (p125FAK) involved in signal transduction pathways used in cell adhesion, motility, and proliferation. Because alterations in these cellular processes are thought to occur in VSMCs during IH, we studied FAK expression in healthy arteries and veins in comparison with that in pathologic vessels containing IH. METHODS: To determine p125FAK expression at the cellular level, we developed a monoclonal antibody that specifically detected FAK in formalin-fixed, paraffin-embedded tissue sections (5 microm) and analyzed the levels of FAK expression in human arteries and veins. Specificity of monoclonal antibody 4.47 was demonstrated by means of immunofluorescence microscopy showing FAK-specific staining at focal adhesions of healthy human vascular smooth muscle cells (AoSMCs). By using immunohistochemistry techniques, we analyzed the expression of p125FAK in 25 adult human vascular tissue samples from individual patients, which contained a histologically confirmed healthy artery, vein, or IH. RESULTS: FAK expression in healthy and pathologic human vascular tissue was localized predominantly within VSMC cytoplasm. In healthy human artery and vein, borderline FAK expression was detected in the media of seven of 17 vessels and undetectable in the remainder of specimens. However, in vessels containing IH, FAK was overexpressed in the pathologic VSMC populations at moderate-to-strong levels in eight of eight specimens. The levels of FAK expression were directly correlated with structures containing IH, and the results of FAK staining intensity and the percentage of positive cells in these samples were significantly increased compared with normal vascular tissue levels (P <.05, Student t test). CONCLUSION: These results provide the first evidence that FAK is overexpressed in VSMCs involved in IH and suggest that FAK upregulation may be part of a mechanism for migration and proliferation of VSMCs during this process. Furthermore, the dramatic upregulation of FAK in IH and the relative lack of expression in healthy vessels suggest that FAK may be a rational target for controlling IH.

Distal thoracic aorta as inflow for the treatment of chronic mesenteric ischemia.

PURPOSE: Mesenteric revascularization for chronic mesenteric ischemia (CMI) traditionally involves antegrade or retrograde bypass graft originating from the supraceliac or infrarenal aorta. The distal thoracic aorta (DTA) may provide a better inflow source than the abdominal aorta. The purpose of this study was to evaluate the results with the DTA used as inflow for the surgical treatment of CMI. METHODS: All patients undergoing mesenteric revascularization for CMI with grafts originating from the DTA were identified from 1990 to 1999. A ninth interspace thoracoretroperitoneal incision was used for exposure, and distal aortic flow was maintained by use of a partial occlusion clamp. RESULTS: Eighteen consecutive patients with CMI underwent mesenteric bypass grafting with the DTA used as inflow. All patients were admitted with chronic abdominal pain or weight loss, with two (12%) requiring urgent revascularization because of acute exacerbation of chronic symptoms. Fourteen (78%) patients had both celiac and superior mesenteric artery bypass grafts placed, and three (17%) patients had superior mesenteric artery grafts alone. There was one (6%) perioperative death and three (17%) major complications. There was no kidney failure, mesenteric infarction, or spinal cord ischemia. The life-table survival rate was 89%, 89%, and 76% at 1, 3, and 5 years, respectively. All 18 patients remained symptom free and required no additional procedures to assist patency. There was no evidence of graft stenosis or occlusion (100% patency) for those grafts evaluated objectively during the mean follow-up of 34.8 months (range, 1-97 months). CONCLUSIONS: Antegrade mesenteric revascularization with the DTA used as inflow is associated with low morbidity and mortality rates. Furthermore, it provides excellent midterm patency and survival results and should be considered as a primary approach for reconstruction of patients with CMI.

Sural artery pseudoaneurysms after knee arthroscopy: treatment with transcatheter embolization.

Vascular injury of the popliteal artery or its branches after knee arthroscopy is a rare but potentially devastating complication. We report two cases of sural artery branch pseudoaneurysms resulting from knee arthroscopy. Both patients were successfully treated with transcatheter embolization of the pseudoaneurysms. the diagnosis and treatment options of this unusual injury are discussed.

The value of air plethysmography in predicting clinical outcome after surgical treatment of chronic venous insufficiency.

PURPOSE: The role of air plethysmography (APG) as a predictor of clinical outcome after surgery in venous disease is yet to be defined. The purpose of this study was to investigate the value of APG in predicting clinical outcome after venous surgery for chronic venous insufficiency (CVI). METHODS: Seventy-three extremities in 71 patients with Class 3 through 6 CVI were assessed preoperatively with CEAP (c linical, e tiologic, a natomic, p athophysiologic) criteria, standing reflux duplex ultrasound scan, and APG with measurements of preoperative venous filling index (VFI), venous volumes, ejection fraction, and residual volume fraction. After surgical treatment of the affected limbs, repeat APG studies were obtained within 6 weeks. Established venous reporting standards were used for follow-up to calculate clinical symptom scores (CSSs) in each patient. RESULTS: Superficial venous reflux occurred alone in 24 limbs or in conjunction with perforator incompetence in 26 limbs. Deep and superficial reflux, with or without perforator incompetence, was found in 16 limbs, and seven limbs had isolated deep insufficiency. Follow-up was available in 60 of 71 patients (mean period, 44.3 months). Postoperative APG demonstrated significant hemodynamic changes after surgery as measured with VFI, venous volumes, ejection fraction, and residual volume fraction. Mean CSSs decreased from 7.35 +/- 0.56 preoperatively to 1.79 +/- 0.32 at late follow-up after surgery (P <.001). With the use of logistic regression, the parameter correlating most closely with clinical outcome was the VFI. A normal postoperative VFI (

Subset-specific regulation of the lymphatic exit of recirculating lymphocytes in vivo.

The blood-to-lymph recirculation of lymphocytes is required for the maintenance of immune surveillance and the dissemination of memory. Although the ability of lymph-borne cells to recirculate has been well documented, relatively less is known about the migration capacity of PBLs. We have found a clear preference for PBLs to recirculate through s.c. rather than intestinal lymph nodes. This preference could be directly attributed to the migratory characteristics of gammadelta-T cells. gammadelta-T cells were found to express significantly higher levels of L-selectin than other subsets, suggesting that at least some of this preferential migration could be attributed to their interaction with ligands on vascular endothelium. More detailed experiments showed that gammadelta-T cells migrated through lymph nodes with greater efficiency than alphabeta T cells or B cells, which clearly indicated an enhanced ability of gammadelta-T cells to exit lymph nodes in the efferent lymph independent of entry from the blood. This hypothesis was supported by histological examination, where gammadelta-T cells were found almost exclusively in the interfollicular traffic areas within lymph nodes. These data indicate that gammadelta-T cells are the most active recirculating lymphocyte subset in ruminants and suggest new mechanisms to regulate the traffic of lymphocyte subsets through normal lymph nodes.

Prospective screening for postoperative deep venous thrombosis in patients undergoing infrainguinal revascularization.

PURPOSE: The incidence of deep venous thrombosis (DVT) in patients undergoing infrainguinal bypass graft procedures has not been well documented, and the need for routine prophylaxis remains controversial. The purpose of this study was to prospectively evaluate the risk of postoperative DVT complicating infrainguinal revascularization. METHODS: Seventy-four patients undergoing infrainguinal bypass graft procedures during a 12-month period were prospectively screened for DVT. Bilateral lower extremity venous duplex scan imaging was performed preoperatively and within 1 week and 6 weeks, postoperatively. Routine DVT prophylaxis was not used, with anticoagulation reserved for specific indications. RESULTS: Of the 74 patients screened, three patients (4.1%) had DVT identified on preoperative venous duplex scan imaging and were excluded from the study. Of the remaining 71 patients enrolled, only two patients (2.8%) had postoperative DVT. Postoperative DVT was ipsilateral to the bypass graft extremity in both patients, with involvement of the peroneal vein in one patient and the femoral vein in the other. Although routine prophylaxis was not used, 18 of these patients (25%) were anticoagulated for other indications, with DVT occurring in one patient (5.6%). Of the remaining 53 patients who did not receive postoperative anticoagulation, only one patient (1.8%) had DVT. CONCLUSIONS: According to this prospective study, the risk of postoperative DVT in patients undergoing infrainguinal revascularization is low. Routine prophylaxis is not recommended, with postoperative anticoagulation reserved for specific indications.

An enhanced role for the recirculating lymphocyte in the neonatal immune system.

Lymphocytes continually recirculate between the blood and the tissues via the lymph independent of antigen. A great deal is known regarding both the physiology and the molecular mechanisms responsible for the process in adults. However, relatively little is known regarding the development of the recirculating lymphocyte pool in very young animals or fetuses. We have directly measured the recirculation of lymphocyte subsets in antigen-inexperienced newborn animals, and found extensive recirculation of T cells through both intestinal and subcutaneous lymph nodes. Apparent selective migration of recirculating lymphocytes could be attributed to subset-specific migration of gammadelta-T cells through subcutaneous lymph nodes. This clearly demonstrates that the preference for gammadelta-T cells to recirculate through SCLN is lineage specific, and independent of the presence of antigen. Most surprising was the observation that the recirculating lymphocyte pool was proportionately larger in neonatal animals than in adults, which correlated with the histological appearance of newborn lymph nodes. This data strongly suggests that development of the recirculating lymphocyte pool is inversely correlated with antigen exposure, and decreases in size with age and the acquisition of immunological memory.

Use of endovascular stents for the treatment of abdominal aortic aneurysm.

The conventional open surgical repair of abdominal aortic aneurysms is a well-established and durable procedure. However, as with all other major abdominal surgical operations, there are associated morbidities. Both mortality and morbidity increase significantly with advanced patient age and associated comorbid conditions. Endovascular aortic stent-grafts offer a significantly less invasive alternative to conventional open-surgical repair. Patients previously considered unsuitable for open repair can often receive treatment for aneurysms with endovascular techniques. The US Food and Drug Administration has recently approved two endovascular stent-graft devices for use within the United States.