Prevalence of elevated serum fatty acid synthase in chronic limb-threatening ischemia.

There are currently no serum-based evaluations that can corroborate the severity of peripheral artery disease (PAD). In this cross-sectional study, we assessed the prevalence of elevated serum fatty acid synthase (cFAS) in patients with chronic limb-threatening ischemia (CLTI) and evaluated the accuracy of its use in detecting this condition. Preoperative fasting serum samples from 87 patients undergoing vascular intervention were collected between October 2014 and September 2016. Median age was 62 years, with 56 (64%) men, and 32 (37%) with CLTI. We found that elevated cFAS content (OR 1.17; 95% CI 1.04-1.31), type 2 diabetes (T2D; OR 5.22; 95% CI 1.77-15.4), and smoking (OR 3.53; 95% CI 1.19-10.5) were independently associated with CLTI and could detect the presence of CLTI with 83% accuracy (95% CI 0.74-0.92). Furthermore, serum FAS content was positively correlated with FAS content in femoral artery plaque in patients with severe PAD ([Formula: see text] = 0.22; P = 0.023). Finally, significantly higher co-localization of FAS and ApoB were observed within lower extremity arterial media (P < .001). Our findings indicate that serum FAS content is a marker for disease severity in patients with PAD, independent of concomitant T2D and smoking, and may play a key role in FAS and ApoB peripheral plaque progression.

Circulating serum fatty acid synthase is elevated in patients with diabetes and carotid artery stenosis and is LDL-associated.

BACKGROUND AND AIMS: Diabetes is an independent risk factor for carotid artery stenosis (CAS). Fatty acid synthase (FAS), an essential de novo lipogenesis enzyme, has increased activity in the setting of diabetes that leads to altered lipid metabolism. Circulating FAS (cFAS) was recently observed in the blood of patients with hyperinsulinemia and cancer. We thought to evaluate the origin of cFAS and its role in diabetes-associated CAS. METHODS: Patients with diabetes and no diabetes, undergoing carotid endarterectomy (CEA) for CAS, were prospectively enrolled for collection of plaque and fasting serum. FPLC was used to purify lipoprotein fractions, and ELISA was used to quantify cFAS content and activity. Immunoprecipitation (IP) was used to evaluate the affinity of cFAS to LDL-ApoB. RESULTS: Patients with CAS had higher cFAS activity (p < 0.01), and patients with diabetes had higher cFAS activity than patients with no diabetes (p < 0.05). cFAS activity correlated with serum glucose (p = 0.03, r2 = 0.35), and cFAS content trended with plaque FAS content (p = 0.06, r2 = 0.69). cFAS was predominantly in LDL cholesterol fractions of patients with CAS (p < 0.001), and IP of cFAS demonstrated pulldown of ApoB. Similar to patients with diabetes, db/db mice had highest levels of serum cFAS (p < 0.01), and fasL-/- (tissue-specific liver knockdown of FAS) mice had the lowest levels of cFAS (p < 0.001). CONCLUSIONS: Serum cFAS is higher in patients with diabetes and CAS, appears to originate from the liver, and is LDL cholesterol associated. We postulate that LDL may be serving as a carrier for cFAS that contributes to atheroprogression in carotid arteries of patients with diabetes.

Amputation stump perfusion is predictive of post-operative necrotic eschar formation.

BACKGROUND: A large proportion of patients develop poor amputation stump healing. We hypothesize that Laser-Assisted Fluorescent Angiography (LAFA) can predict inadequate tissue perfusion and healing. METHODS: Over an 8-month period we reviewed all patients who underwent lower extremity amputation and LAFA. We evaluated intra-operative LAFA global and segmental stump perfusion, and post-operative modified Bates-Jensen (mBJS) wound healing scores. RESULTS: In 15 patients, amputation stumps with lower global perfusion demonstrated higher mBJS (P = 0.01). Lower suture-line perfusion also correlated with more eschar formation (P < 0.001). Diabetic patients had higher mBJS (P = 0.009), lower stump perfusion (P = 0.02), and increased eschar volume (P < 0.001). CONCLUSION: LAFA is a useful adjunct for intra-operative stump perfusion assessment and can predict areas of poor stump healing and eschar formation. Diabetic patients seem to be at higher risk of stump eschar formation.

Management of Cavoatrial Deep Venous Thrombosis: Incorporating New Strategies.

Cavoatrial deep venous thrombosis (DVT) is diagnosed with increasing prevalence. It can be managed medically with anticoagulation or with directed interventions aimed to efficiently reduce the thrombus burden within the target venous segment. The type of management chosen depends greatly on the etiology and chronicity of the thrombosis, existing patient comorbidities, and the patient's tolerance to anticoagulants and thrombolytic agents. In addition to traditional percutaneous catheter-based pharmacomechanical thrombolysis, other catheter-based suction thrombectomy techniques have emerged in recent years. Each therapeutic modality requires operator expertise and a coordinated care paradigm to facilitate successful outcomes. Open surgical thrombectomy is alternatively reserved for specific patient conditions, including intolerance of anticoagulation, failed catheter-based interventions, or acute emergencies.

Lack of identifiable biologic behavior in a series of porcine mesh explants.

INTRODUCTION: Biologic matrices used in abdominal wall reconstruction are purported to undergo remodeling into connective tissue resembling native collagen. Key steps in that process include inflammatory response at the mesh/tissue interface, cellular penetration, and neovascularization of the matrix, followed by fibroblast proliferation and collagen deposition. We aimed to examine the concept of biologic mesh remodeling/regeneration in a series of explanted porcine biologic meshes. MATERIALS AND METHODS: A cohort of patients who underwent removal of porcine biologic mesh was identified in a prospective database. Mesh/tissue samples were analyzed using standard hematoxylin/eosin and Masson's trichrome staining. Main outcome measures included: inflammatory response at the mesh/tissue interface, foreign body reaction (FBR), cellular penetration, neovascularization, and new collagen deposition. All evaluations were performed by a blinded senior pathologist using established grading scales. RESULTS: A total of 14 cases with implant time ranging from 4 to 33 months were identified and analyzed. All meshes were placed as intraperitoneal underlay. There were 7 non-cross-linked and 7 cross-linked grafts. Cross-linked grafts were associated with mild FBR and moderate fibrous capsule formation. Similarly, non-cross-linked grafts had mild-to-moderate FBR and encapsulation. Furthermore, non-cross-linked grafts were associated with no neovascularization and minimal peripheral mesh neocellularization. Cross-linked grafts demonstrated neither neovascularization nor neocellularization. Although no grafts were associated with any quantifiable new collagen deposition within the porcine biologic matrix, minimal biodegradation/remodeling was observed at the periphery of the non-cross-linked grafts only. CONCLUSION: The biologic behavior of porcine meshes is predicated on their ability to undergo mesh remodeling with resorption and new collagen deposition. In the largest series of human biologic explants, we detected no evidence of xenograft remodeling, especially in the cross-linked group. Although underlay mesh placement and other patient factors may have contributed to our findings, the concept of porcine biologic mesh regeneration does not seem to be prevalent in the clinical setting.

Comparative radiographic analysis of changes in the abdominal wall musculature morphology after open posterior component separation or bridging laparoscopic ventral hernia repair.

BACKGROUND: Large ventral hernias are known to induce atrophic changes to the anterior abdominal wall musculature. We have shown that anterior component separation with external oblique (EO) release, with resultant reconstruction of the midline, results in hypertrophy of the rectus muscle (RM), internal oblique (IO), and transversus abdominis (TA). We aimed to compare and contrast the impact of posterior component separation with transversus abdominis release (TAR) and bridging laparoscopic ventral hernia repair (LVHR) on the muscles of the abdominal wall. STUDY DESIGN: Preoperative and at least 6-month postoperative CT scans were analyzed for patients undergoing TAR with midline reconstruction and LVHR without midline reconstruction. A change in the measured area of each abdominal wall muscle was used as the determinant of hypertrophy or atrophy. The areas of the RM, EO, IO, and TA were measured at the L3 to L4 level through the axial plane. RESULTS: Twenty-five consecutive patients with pre- and postoperative images were analyzed in each group. In the TAR group, the RA, EO, and IO demonstrated significant increases in area. In the LVHR group, no muscles demonstrated any significant changes. CONCLUSIONS: Similar to anterior component separation, hernia repair with TAR results in hypertrophy of the rectus abdominis muscle. In addition, we found that TAR was associated with hypertrophy of both external and internal oblique muscles. Bridging repair during LVHR, on the other hand, did not result in any significant changes in any of the abdominal muscles. Our findings provide clear radiologic evidence that re-creation of the midline by means of the TAR leads to improved anatomy of the abdominal wall, in addition to positive compensatory changes of the lateral abdominal wall musculature.