Brandon J. Sumpio

Contemporary assessment of foot perfusion in patients with critical limb ischemia

Significant progress in limb salvage for patients with peripheral arterial disease and critical limb ischemia has occurred in the past 2 decades. Improved patient outcomes have resulted from increased knowledge and understanding of the disease processes, as well as efforts to improve revascularization techniques and enhance patient care after open and endovascular procedures. An imaging modality that is noninvasive, fast, and safe would be a useful tool for clinicians in assessing lower-extremity perfusion when planning interventions. Among the current and emerging regional perfusion imaging modalities are transcutaneous oxygen monitoring, hyperspectral imaging, indocyanine green dye-based fluorescent angiography, nuclear diagnostic imaging, and laser Doppler. These tests endeavor to delineate regional foot perfusion to guide directed revascularization therapy in patients with critical limb ischemia and foot ulceration.

Prosthetic Options Available for the Diabetic Lower Limb Amputee

Although the rate of lower limb amputation in patients with diabetes is decreasing, amputation still remains a major complication of diabetes. Prosthetics have been long used to help amputees ambulate. The last decade has seen many advances in prostheses with the enhanced understanding of the mechanics of ambulation and improved use of technology. This review describes the different types of prosthetic options available for below knee, ankle, and foot amputees, emphasizing the latest advances in prosthetic design.

A Comparison of Immediate Postoperative Rigid and Soft Dressings for Below-Knee Amputations

BACKGROUND A variety of postsurgical dressings are used after a below-knee amputation (BKA), but there is no evidence-based guideline on which dressing to use. The purpose of this study was to compare the application of immediate postoperative rigid dressings or soft dressings on the healing times of BKA. METHODS In this retrospective analysis we compared 151 patients who underwent BKA from 2000 to 2012 at Yale New Haven Hospital. Patient demographics were collected and the type of postoperative dressing utilized was recorded. Ninety-one patients received a rigid plaster or plastic dressing and 60 received a soft gauze dressing with knee immobilizer. Time was measured between amputation and initial casting of prosthesis. RESULTS Average age for the rigid dressing group was 58.6 years, with 78.2% presenting with diabetes mellitus, compared with the soft dressing group of 61.0 years, with 82.8%, respectively. Using a Kaplan-Meier analysis, patients fit with a rigid dressing demonstrated significantly decreased healing time from BKA to initial casting for a prosthesis (P = 0.02). After the first 60 days, 58.24% of patients who received a rigid dressing were ready to be cast, compared with 38.33% of patients receiving a soft dressing (P = 0.03). CONCLUSIONS Below-knee amputees had a significantly quicker healing time, as measured by the time to be cast for prosthesis, when a rigid dressing was used compared with a soft dressing. Consideration should be given to the use of a rigid dressing after BKA to expedite healing and promote earlier ambulation.

Effect of Pulsatile and Continuous Flow on Yes-Associated Protein

Yes-associated protein (YAP) is a mechanosignaling protein that relays mechanical information to the nucleus by changing its level of phosphorylation. We hypothesize that different flow patterns show differential effect on phosphorylated YAP (pYAP) (S127) and total YAP and could be responsible for flow dependent localization of atherosclerosis. Confluent human umbilical vein endothelial cells (HUVECs) seeded on fibronectin-coated glass slides were exposed to continuous forward flow (CFF) and pulsatile forward flow (PFF) using a parallel plate flow chamber system for 30 minutes. Cell lysates were prepared and immunoblotted to detect the levels of phosphorylated YAP and total YAP. HUVECs exposed to both PFF and CFF showed a mild decrease in the levels of both pYAP (S127) and total YAP. While the levels of pYAP (S127) decreased to 87.85 and 85.21% of static control with PFF and CFF, respectively, the levels of total YAP significantly decreased to 91.31 and 92.27% of static control. No significant difference was seen between CFF and PFF on their effect on pYAP (S127), but both conditions resulted in a significant decrease in total YAP at 30 minutes. The results of this experiment show that the possible effect of different types of flow on YAP is not induced before 30 minutes. Experiments exposing endothelial cells to various types of flow for longer duration of time could help to elucidate the role of YAP in the pathogenesis of atherosclerosis.

Indian Spices for the Management of Diabetic Foot Complications

Despite significant advances in medicine and surgery, the prevalence of diabetic foot complications still remains high in both developed and developing countries of the world. Curcumin, the active component of turmeric, an Indian spice has been extensively studied and is known to possess many biological activities including wound healing. The current review describes the available evidence on the utility of curcumin in treating diabetic foot ulcers.

Shear Stress Induces Change in Extracellular Signal-Regulated Kinase 5 Levels with Sustained Activation under Disturbed and Continuous Laminar Flow

&NA; Extracellular signal‐regulated kinase 5 (ERK5) has been reported to regulate endothelial integrity and protect from vascular dysfunction under laminar flow. Previously reported research indicates that under laminar flow ERK5 is activated with production of atheroprotective molecules. However, the characterization of ERK5 activation and levels under different flow patterns has not been investigated. Confluent HUVECs were serum‐starved then seeded on glass slides. HUVECs incubated in 1% FBS were exposed to continuous laminar flow (CLF), to‐and‐fro flow (TFF), or pulsatile forward flow (PFF) in a parallel plate flow chamber. At the end of experimentation, cell lysates were immunoblotted with antibodies to phospho‐ERK5 and total ERK5. ERK5 activation was assessed by the levels of phosphorylated ERK5. The densitometric mean ± SEM is calculated and analyzed by ANOVA. p < 0.05 is considered significant. Levels of ERK5 decreased with all flow conditions with the largest decrease in TFF flow condition. TFF and CLF exhibited sustained ERK5 phosphorylation in HUVECs stimulated for up to 4 hours. PFF had transient phosphorylation of ERK5 at 2 hours, which then became undetectable at 4 hours of exposure to flow. Also, TFF and CLF both showed decreased levels at 4 hours, suggesting a decrease in activation for these flow conditions. Exposure of HUVEC to different types of shear stress results in varying patterns of activation of ERK5. Activation of ERK5 with TFF suggests a role in the pathogenesis of atherosclerosis and vascular remodeling under disturbed flow conditions.

African Trypanosome-Induced Blood-Brain Barrier Dysfunction under Shear Stress May Not Require ERK Activation.

African trypanosomes are tsetse fly transmitted protozoan parasites responsible for human African trypanosomiasis, a disease characterized by a plethora of neurological symptoms and death. How the parasites under microvascular shear stress (SS) flow conditions in the brain cross the blood-brain barrier (BBB) is not known. In vitro studies using static models comprised of human brain microvascular endothelial cells (BMEC) show that BBB activation and crossing by trypanosomes requires the orchestration of parasite cysteine proteases and host calcium-mediated cell signaling. Here, we examine BMEC barrier function and the activation of extracellular signal-regulated kinase (ERK)1/2 and ERK5, mitogen-activated protein kinase family regulators of microvascular permeability, under static and laminar SS flow and in the context of trypanosome infection. Confluent human BMEC were cultured in electric cell-substrate impedance sensing (ECIS) and parallel-plate glass slide chambers. The human BMEC were exposed to 2 or 14 dyn/cm(2) SS in the presence or absence of trypanosomes. Real-time changes in transendothelial electrical resistance (TEER) were monitored and phosphorylation of ERK1/2 and ERK5 analyzed by immunoblot assay. After reaching confluence under static conditions human BMEC TEER was found to rapidly increase when exposed to 2 dyn/cm(2) SS, a condition that mimics SS in brain postcapillary venules. Addition of African trypanosomes caused a rapid drop in human BMEC TEER. Increasing SS to 14 dyn/cm(2), a condition mimicking SS in brain capillaries, led to a transient increase in TEER in both control and infected human BMEC. However, no differences in ERK1/2 and ERK5 activation were found under any condition tested. African trypanosomiasis alters BBB permeability under low shear conditions through an ERK1/2 and ERK5 independent pathway.

Endovascular interventions decrease length of hospitalization and are cost-effective in acute mesenteric ischemia

Objective: Acute mesenteric ischemia (AMI) continues to be one of the most devastating diagnoses requiring emergent vascular intervention. There is a national trend toward increased use of endovascular procedures, with improved survival for the treatment of these patients. Our aim was to evaluate whether this trend has changed the treatment of AMI and the subsequent impact on length of hospitalization and hospitalization costs. Methods: We identified all patients admitted for AMI from the National Inpatient Sample from 2004 to 2014 who received open surgical revascularization (OPEN) or an endovascular intervention (ENDO). Primary end points included length of hospital stay and cost of hospitalization. Our secondary end points included acute kidney injury (AKI), in‐hospital mortality, and routine discharge. Results: Among 10,381 discharges identified in the data set, 3833 (37%; 97.5% confidence interval [CI], 35%‐39%) were male patients with a mean age of 69 years (range, 18‐98 years); 4543 (44%; 97.5% CI, 41%‐47%) patients were treated ENDO, and 5839 (56%; 97.5% CI, 53%‐59%) patients were treated OPEN. Although a higher proportion of patients in the ENDO group (28%; 97.5% CI, 24%‐31%) vs the OPEN group (14%; 97.5% CI, 11%‐16%) had a moderate to severe Charlson Comorbidity Index (P < .0001), ENDO was associated with a lower mortality rate (12.3% [97.5% CI, 9.8%‐14.8%] vs 33.1% [97.5% CI, 29.9%‐36.2%]; P < .0001) and a lower mean hospitalization cost (

Increased mortality in octogenarians treated for lifestyle limiting claudication

41,615 [97.5% CI,

Acute Limb Ischemia in an 8-Year-Old Patient: A Case Report

38,663‐