Safety and Efficacy of Percutaneous Translumbar Inferior Vena Cava Catheters: A Systematic Review and Meta-Analysis.

PURPOSE: To examine the reported adverse events associated with inferior vena cava (IVC) catheterization and investigate the reasons for discrepancies between reports. MATERIALS AND METHODS: Cochrane Library trials register, PubMed, Embase, and Scopus databases were systematically searched for studies that included any terms of IVC and phrases related to catheters or central access. Of the 5,075 searched studies, 137 were included in the full-text evaluation. Of these, 37 studies were included in the systematic review, and the adverse events reported in 16 of these 37 identified studies were analyzed. An inverse-variance random-effects model was used to conduct the meta-analysis. Outcomes were summarized by the incidence rate (IR) and 95% CI. RESULTS: Compared with that of catheters <10 F in size (IR, 0.08; 95% CI, 0.03-0.12), the incidence of catheter-related infections per 100 catheter days was 0.2 more for catheters ≥10 F in size (IR, 0.28; 95% CI, 0.25-0.31). In addition, dual-lumen catheters showed 0.13 more malfunction per 100 catheter days (IR, 0.27; 95% CI, 0.16-0.37) than that shown by single-lumen catheters (IR, 0.14; 95% CI, 0.09-0.19). Both differences were statistically significant. Other adverse events were malposition (IR, 0.04; 95% CI, 0.04-0.05), fracture (IR, 0.01; 95% CI, 0.00-0.02), kinking (IR, 0.01; 95% CI, 0.00-0.01), replaced catheter (IR, 0.2; 95% CI, 0.1-0.31), removal (IR, 0.13; 95% CI, 0.1-0.16), IVC thrombosis (IR, 0.01; 95% CI, 0.00-0.03), and retroperitoneal hematoma (IR, 0.01; 95% CI, 0.00-0.01), all per 100 catheter days. CONCLUSIONS: Translumbar IVC access is an option for patients with exhausted central veins. Small-caliber catheters cause fewer catheter-related infections, and single-lumen catheters function longer.

The Dynamic Platelet Transcriptome in Obesity and Weight Loss.

OBJECTIVE: Adiposity is associated with oxidative stress, inflammation, and glucose intolerance. Previous data suggest that platelet gene expression is associated with key cardiometabolic phenotypes, including body mass index but stable in healthy individuals over time. However, modulation of gene expression in platelets in response to metabolic shifts (eg, weight reduction) is unknown and may be important to defining mechanism. Approach and Results: Platelet RNA sequencing and aggregation were performed from 21 individuals with massive weight loss (>45 kg) following bariatric surgery. Based on RNA sequencing data, we measured the expression of 67 genes from isolated platelet RNA using high-throughput quantitative reverse transcription quantitative PCR in 1864 FHS (Framingham Heart Study) participants. Many transcripts not previously studied in platelets were differentially expressed with bariatric surgical weight loss, appeared specific to platelets (eg, not differentially expressed in leukocytes), and were enriched for a nonalcoholic fatty liver disease pathway. Platelet aggregation studies did not detect alteration in platelet function after significant weight loss. Linear regression models demonstrated several platelet genes modestly associated with cross-sectional cardiometabolic phenotypes, including body mass index. There were no associations between studied transcripts and incident diabetes or cardiovascular end points. CONCLUSIONS: In summary, while there is no change in platelet aggregation function after significant weight loss, the human platelet experiences a dramatic transcriptional shift that implicates pathways potentially relevant to improved cardiometabolic risk postweight loss (eg, nonalcoholic fatty liver disease). Further studies are needed to determine the mechanistic importance of these observations.

A systematic review of the quality of cardiovascular surgery studies that extracted data from the MAUDE database.

OBJECTIVE: To investigate opportunities and limitations of using the Manufacturer and User Facility Device Experience (MAUDE) database for cardiovascular surgery research, we analyzed the quality of studies having ever used MAUDE, in the field of cardiovascular surgery. METHODS: We systematically searched the Cochrane Library, PubMed, EMBASE, and Google Scholar for randomized and nonrandomized studies, from inception to July 2019. Two authors evaluated the quality of the retrieved observational studies, according to the National Institutes of Health quality assessment tool for either case series or cross-sectional studies. These tools quantify the quality of case series and cohorts/cross-sectional studies, respectively, with nine and 14 queries. RESULTS: Fifty-eight studies were included in the final qualitative review. Of 58 identified studies, 32 were case series, 8 were abstracts of case series, and 13 were reviews or case discussion with an included series from MAUDE. Also, five articles were cross-sectional studies. Of the 32 formal case series, 26 (81%) were found to have poor quality. The most common reasons for a poor quality designation included a lack of consecutive participants, undetermined comparability of participants, and undetermined follow-up adequacy. Only one out of five cross-sectional studies had fair quality; four others were evaluated as poor quality studies. CONCLUSIONS: Cardiovascular surgery studies using the MAUDE database, whether case series or cross-sectional design, are mostly of poor quality. Their low quality is partly caused by poor study design, but mainly by intrinsic limitations to the MAUDE database: cases recruited are not consecutive; patient characteristics are not detailed enough to allow a meaningful comparison of patient characteristics between different patient entries; outcome measures are unclear; there is a limited follow-up; and time-to-event data are lacking. We conclude that the quality of cardiovascular surgery publications that rely on data from MAUDE could be improved if investigators were to extract all relevant data points from MAUDE entries, then apply standard quality assessment tools in compiling and reporting the data. MAUDE might be improved if it used medical case report standards during the process of reporting and indexing adverse events. To calculate the incidence rate of any adverse event, all event-free cases, as well as all adverse events in patients using a device, are required. Neither of these two variables is available in the MAUDE at the time of writing.

A systematic review and meta-analysis of predilation and postdilation in transfemoral carotid artery stenting.

OBJECTIVE: In this review, we evaluate the short-term impact of different ballooning combinations on hemodynamic instability neurologic events, and mortality associated with carotid artery stenting. METHODS: We used a search strategy to identify studies in the Cochrane Library trials register, PubMed, EMBASE, Google Scholar, and the US National Library of Medicine clinical trial databases up to May 2019. Studies reporting either hemodynamic instability, neurologic events, or mortality were included according to the recommendations of the Preferred Reporting Items for Systematic reviews and Meta-analysis. Fixed and random models were used to summarize the effects. RESULTS: Of seven included cohort studies for qualitative review, six were selected for meta-analysis. Patients without postdilation had significantly less hemodynamic instability in the random effects model (risk ratio, 0.53; 95% confidence interval, 0.37-0.77; P = .001). Regardless of the dilation type, the overall summary effect in the fixed model showed a significant decrease in the risk of developing short-term neurologic events (risk ratio, 0.67; 95% confidence interval, 0.47-0.97; P = .03). Last, the exclusion of either of the two dilation techniques had no significant effect on mortality. CONCLUSIONS: Avoiding postdilation reduces perioperative hemodynamic instability and this benefit lasts at least up to 30 days. Regardless of the type, fewer dilations during carotid artery stenting possibly decreases the neurologic events during and 30 days after the procedure. The data also suggest that the residual stenoses above current practiced standard may provide a safer threshold to prompt postdilation. Statements about the long-term effects of dilation techniques requires more study.

Proteins Altered by Surgical Weight Loss Highlight Biomarkers of Insulin Resistance in the Community.

Objective- Mechanisms of early and late improvements in cardiovascular risk after bariatric surgery and applicability to larger, at-risk populations remain unclear. We aimed to identify proteins altered after bariatric surgery and their relations to metabolic syndrome and diabetes mellitus. Approach and Results- We identified 19 proteins altered in 32 nonfasting plasma samples from a study of patients undergoing bariatric surgery who were evaluated preoperatively (visit 1) versus both early (visit 2; ≈3 months) and late (visit 3; ≈12 months) postoperative follow-up using predefined protein panels (Olink). Using in silico methods and publicly available gene expression repositories, we found that genes encoding 8 out of 19 proteins had highest expression in liver relative to other assayed tissues, with the top biological and disease processes, including major obesity-related vascular diseases. Of 19 candidate proteins in the surgical cohort, 6 were previously measured in >3000 FHS (Framingham Heart Study) participants (IGFBP [insulin-like growth factor binding protein]-1, IGFBP-2, P-selectin, CD163, LDL (low-density lipoprotein)-receptor, and PAI [plasminogen activator inhibitor]-1). A higher concentration of IGFBP-2 at baseline was associated with a lower risk of incident metabolic syndrome (odds ratio per log-normal unit, 0.45; 95% CI, 0.32-0.64; P=7.7×10-6) and diabetes mellitus (odds ratio, 0.63; 95% CI, 0.49-0.79; P=0.0001) after multivariable adjustment. Conclusions- Using a directed protein quantification platform (Olink), we identified known and novel proteins altered after surgical weight loss, including IGFBP-2. Future efforts in well-defined obesity intervention settings may further define and validate novel targets for the prevention of vascular disease in obesity.

Histology and Biaxial Mechanical Behavior of Abdominal Aortic Aneurysm Tissue Samples.

Abdominal aortic aneurysms (AAAs) represent permanent, localized dilations of the abdominal aorta that can be life-threatening if progressing to rupture. Evaluation of risk of rupture depends on understanding the mechanical behavior of patient AAA walls. In this project, a series of patient AAA wall tissue samples have been evaluated through a combined anamnestic, mechanical, and histopathologic approach. Mechanical properties of the samples have been characterized using a novel, strain-controlled, planar biaxial testing protocol emulating the in vivo deformation of the aorta. Histologically, the tissue ultrastructure was highly disrupted. All samples showed pronounced mechanical stiffening with stretch and were notably anisotropic, with greater stiffness in the circumferential than the axial direction. However, there were significant intrapatient variations in wall stiffness and stress. In biaxial tests in which the longitudinal stretch was held constant at 1.1 as the circumferential stretch was extended to 1.1, the maximum average circumferential stress was 330 ± 70 kPa, while the maximum average axial stress was 190 ± 30 kPa. A constitutive model considering the wall as anisotropic with two preferred directions fit the measured data well. No statistically significant differences in tissue mechanical properties were found based on patient gender, age, maximum bulge diameter, height, weight, body mass index, or smoking history. Although a larger patient cohort is merited to confirm these conclusions, the project provides new insight into the relationships between patient natural history, histopathology, and mechanical behavior that may be useful in the development of accurate methods for rupture risk evaluation.

Matrix- and plasma-derived peptides promote tissue-specific injury responses and wound healing in diabetic swine.

BACKGROUND: Non-healing wounds are a major global health concern and account for the majority of non-traumatic limb amputations worldwide. However, compared to standard care practices, few advanced therapeutics effectively resolve these injuries stemming from cardiovascular disease, aging, and diabetes-related vasculopathies. While matrix turnover is disrupted in these injuries, debriding enzymes may promote healing by releasing matrix fragments that induce cell migration, proliferation, and morphogenesis, and plasma products may also stimulate these processes. Thus, we created matrix- and plasma-derived peptides, Comb1 and UN3, which induce cellular injury responses in vitro, and accelerate healing in rodent models of non-healing wounds. However, the effects of these peptides in non-healing wounds in diabetes are not known. Here, we interrogated whether these peptides stimulate healing in a diabetic porcine model highly reminiscent of human healing impairments in type 1 and type 2-diabetes. METHODS: After 3-6 weeks of streptozotocin-induced diabetes, full-thickness wounds were surgically created on the backs of adult female Yorkshire swine under general anesthesia. Comb1 and UN3 peptides or sterile saline (negative control) were administered to wounds daily for 3-7 days. Following sacrifice, wound tissues were harvested, and quantitative histological and immunohistochemical analyses were performed for wound closure, angiogenesis and granulation tissue deposition, along with quantitative molecular analyses of factors critical for angiogenesis, epithelialization, and dermal matrix remodeling. RESULTS: Comb1 and UN3 significantly increase re-epithelialization and angiogenesis in diabetic porcine wounds, compared to saline-treated controls. Additionally, fluorescein-conjugated Comb1 labels keratinocytes, fibroblasts, and vascular endothelial cells in porcine wounds, and Far western blotting reveals these cell populations express multiple fluorescein-Comb1-interacting proteins in vitro. Further, peptide treatment increases mRNA expression of several pro-angiogenic, epithelializing, and matrix-remodeling factors, importantly including balanced inductions in matrix metalloproteinase-2, -9, and tissue inhibitor of metalloproteinases-1, lending further insight into their mechanisms. CONCLUSIONS: Comb1 and UN3 stimulate wound resolution in diabetic Yorkshire swine through upregulation of multiple reparative growth factors and cytokines, especially matrix metalloproteinases and inhibitors that may aid in reversing the proteolytic imbalance characteristic of chronically inflamed non-healing wounds. Together, these peptides should have great therapeutic potential for all patients in need of healing, regardless of injury etiology.

Twenty-year analysis of trends in the incidence and in-hospital mortality for lower-extremity arterial thromboembolism.

BACKGROUND: Epidemiology data for lower-extremity arterial thromboembolism (LET) are limited and may result from either acute limb ischemia or an acute exacerbation of critical limb ischemia. Given marked changes in both diagnosis and therapy over the last 2 decades, we hypothesized that this time period would have witnessed reductions in both the incidence and in-hospital mortality of LET. METHODS AND RESULTS: Data from 1988 through 2007 from the National Hospital Discharge Survey were analyzed. All admissions for patients with LET were extracted, and the respective International Classification of Diseases, Ninth Revision, Clinical Modification codes were internally validated for both LET and acute limb ischemia. Descriptive statistics were used. The validity of the codes was good for identifying LET cases but poor for identifying acute limb ischemia cases because many of these acute presentations were attributable to critical limb ischemia. Over the 20-year span, there were 1.76 million cases of LET. The incidence of LET decreased significantly from 42.4 per 100 000 persons between 1988 and 1997 to 23.3 per 100 000 persons between 1998 and 2007. The in-hospital mortality for LET decreased significantly from 8.28% between 1988 and 1997 to 6.34% between 1998 and 2007, and male patients achieved greater mortality reduction compared with female patients. Treatments for acute limb ischemia showed decreasing use of surgical bypass and amputation and increasing rates of catheter-based thrombolysis. CONCLUSIONS: Over the 20-year study period, there have been significant reductions in both LET incidence and in-hospital mortality. Unfortunately, LET admissions extracted from an administrative database comprise a diverse group of individuals, including those with acute and chronic forms of limb ischemia and iatrogenic arterial injury, limiting the true assessment of ALI incidence.

Characterization of the plasma metabolome and lipidome in response to sleeve gastrectomy and gastric bypass surgeries reveals molecular patterns of surgical weight loss.

OBJECTIVES: Bariatric surgery improves metabolic health, but the underlying mechanisms are not fully understood. We analyzed the effects of two types of bariatric surgery, sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB), on the plasma metabolome and lipidome. METHODS: We characterized the plasma metabolome (1268 metabolites) and lipidome (953 lipids) pre-operatively and at 3 and 12 months post-operatively in 104 obese adults who were previously recruited to a prospective cohort of bariatric surgery. The metabolomic and lipidomic responses to bariatric surgery over time were analyzed using multivariable linear mixed-effects models. RESULTS: There were significant changes in multiple metabolites and lipids, including rapid early changes in amino acid and peptide metabolites, including decreases in branched-chain amino acids (BCAAs), aromatic AAs, alanine and aspartate, and increases in glycine, serine, arginine and citrulline. There were also significant decreases in many triglyceride species, with increases in phosphatidylcholines and phosphatidylethanolamines. There were significant changes in metabolites related to energy metabolism that were apparent only after 12 months. We observed differences by bariatric surgery type in the changes in a small number of primary and secondary bile acids, including glycohyocholate and glyco-beta-muricholate. CONCLUSIONS: Our findings highlight the comprehensive changes in metabolites and lipids that occur over the 12 months following bariatric surgery. While both SG and RYGB caused profound changes in the metabolome and lipidome, RYGB was characterized by greater increases in bile acids following surgery.

Defining the radiation "scatter cloud" in the interventional suite.

OBJECTIVE: We hypothesized that fluoroscopic imaging creates radiation fields that are unevenly scattered throughout the endovascular suite. We sought to quantify the radiation dose spectrum at various locations during imaging procedures and to represent this in a clinically useful manner. METHODS: Digital subtraction imaging (Innova 4100; GE Healthcare, Waukesha, Wisc) of the abdomen and pelvis was performed on a cadaver in anteroposterior, left lateral, and right anterior oblique 45° projections. Radiation exposure was monitored in real time with DoseAware dosimeters (Phillips, Houston, Tex) in eight radial projections at distances of 2, 4, and 6 ft from the center of the imaged field, each at 5-ft heights from the floor. Three to five consecutive data points were collected for each location. RESULTS: At most positions around the angiographic table, radiation exposure decreased as the distance from the source emitter increased; however, the intensity of the exposure varied dramatically around the axis of imaging. With anteroposterior imaging, the radiation fields have symmetric dumbbell shapes, with maximal exposure perpendicular to the table at the level of the gantry. Peak levels at 4 and 6 ft from the source emitter were 2.4 times and 3.4 times higher, respectively, than predicted based on the inverse square law. Maximal radiation exposure was measured in the typical operator position 2 ft away and perpendicular to the table (4.99 mSv/h). When the gantry was rotated 45° and 90°, the radiation fields shifted, becoming more asymmetric, with increasing radiation doses to 10.9 and 69 mSv/h, respectively, on the side of the emitter. Minimal exposure is experienced along the axis of the table, decreasing with distance from the source (<0.77 mSv/h). CONCLUSIONS: Quantifiable and reproducible radiation scatter is created during interventional procedures. Radiation doses vary widely around the perimeter of the angiography table and change according to imaging angles. These data are easily visualized using contour plots and scatter three-dimensional mesh plots. Rather than the concentric circles predicted by the inverse square law, these data more closely resemble a "scatter cloud." Knowledge of the actual exposure levels within the endovascular environment may help in mitigating these risks to health care providers.

Endovascular treatment of stenoses in a pediatric patient with incomplete aortic duplication, mesenteric ischemia, and renovascular hypertension.

Variations in abdominal aortic anatomy may have significant implications in various surgical procedures. We report here a pediatric patient with symptoms of chronic mesenteric ischemia, labile hypertension, and lower extremity claudication. Angiography revealed a partially duplicated aorta with the anterior aorta containing the splanchnic and renal arteries and the posterior segment perfusing the lower extremities. She was successfully treated with balloon angioplasty of two focal stenoses and is normotensive without abdominal symptoms at 1-year follow-up. To our knowledge, this is the first report of a successful endovascular intervention in a partially duplicated aorta.

A systematic review of routine post operative screening duplex ultrasound after thermal and non-thermal endovenous ablation.

OBJECTIVE: The Society of Vascular Surgery and the American Venous Forum recommend duplex ultrasound (DUS) following endovenous ablation. However, this screening may not be cost-effective or clinically indicated. The most common abnormal finding, endovenous heat-induced thrombosis (EHIT level 1-2), represents extension of thrombus from the saphenous <50% across the femoral or popliteal vein, which is thought to have a benign course regardless of intervention. The likelihood of venous thromboembolism (VTE) after thermal and non-thermal ablations was explored to determine the utility of routine postoperative DUS. METHODS: This is an updated and expanded systematic review including data from randomized trials and large observational studies (≥150 patients) of thermal and non-thermal ablations, examining the incidence of VTE. Using PubMed and EMBASE, 4584 publications were screened from 2000 through 2020. After applying inclusion and exclusion criteria, 72 studies were included. Random effects DerSimonian-Laird method was conducted to obtain the pooled incidence. We calculated the number of tests needed to detect one VTE, and the cost was derived from Center for Medicare Services tables. RESULTS: A total of 31,663 patients were included. The pooled incidence of EHIT II-IV, deep venous thrombosis (DVT), and pulmonary embolism (PE) was 1.32% (95% confidence interval [CI], 0.75%-2.02%); DVT (excluding EHIT), 0.20% (95% CI, 0.0%-0.2%); EHIT (I-IV), 2.51% (95% CI, 1.54%-3.68%); and EHIT (II-IV), 1.00% (95% CI, 0.51%-1.61%). There was no mortality. There was a lower DVT rate in thermal vs non-thermal ablations (0.23% vs 0.43%; P = .02); however, for all VTE (EHIT I-IV + DVT + PE), thermal techniques had more thrombosis (2.5% vs 0.5%; P <.001). When clinical significance is defined as DVT + EHIT (II-IV), 175 studies are needed to identify one VTE, costing $21,813 per "significant VTE." Patients receiving pharmacological prophylaxis had less EHIT I-IV compared with those who did not (3.04% vs 1.63%; P < .001); those who received DUS during the first post-op week had three times higher EHIT incidence compared with those whose first DUS was >7 days postoperative (6.6% vs 2.4%; P < .001). CONCLUSIONS: For thermal and non-thermal endovenous ablations, the incidence of VTE diagnosed with routine DUS is small and without clear clinical significance but caries a high cost. The Society of Vascular Surgery and the American Venous Forum recommendation to perform DUS within 72 hours is not justified by these data. We recommend a more targeted post-ablation scanning protocol including symptomatic patients and those at high risk.

Minimizing radiation exposure to the vascular surgeon.

OBJECTIVES: To determine radiation exposure for members of an endovascular surgery team during imaging procedures by varying technique. METHODS: Digital subtraction angiography imaging of the abdomen and pelvis (Innova 4100; GE, Fairfield, Conn) was performed on cadavers, varying positioning and technique within the usual bounds of clinical practice. Radiation exposure was monitored in real-time with dosimeters (DoseAware; Philips, Andover, Mass) to simulate the position of the operator, assistant, and anesthesiologist. The DoseAware system reports radiation exposure in 1-second intervals. Three to five consecutive data points were collected for each imaging configuration. RESULTS: Operator radiation exposure is minimized with detector-to-patient distance <5 cm (2.1 mSv/h) in contrast to 10 to 15 cm (2.8 mSv/h); source-to-image distance of <15 cm (2.3 mSv/h) in contrast to 25 cm (3.3 mSv/h). Increasing image magnification from 0 (2.3 mSv/h) to 3 (0.83 mSv/h) decreases operator exposure by 74%. Increasing linear image collimation from 0 (2.3 mSv/h) to 10 cm (0.30 mSv/h) decreases operator exposure by 87%. The anesthesiologist's radiation exposure is 11% to 49% of the operator's, greatest in the left anterior oblique (LAO) 90 degree projection. The assistant's radiation exposure is 23% to 46% of the operator's. The highest exposure to the operator was noted to be in the LAO 90 degree projection (30.3 mSv/h) and lowest exposure with 10-cm vertical collimation (0.28 mSv/h). CONCLUSIONS: Varying imaging techniques results in different radiation exposure to members of an endovascular surgery team. Knowledge of the variable intensity of radiation exposure may allow modification of the technique to minimize radiation exposure to the team while providing suitable imaging.

Improved amputation-free survival in unreconstructable critical limb ischemia and its implications for clinical trial design and quality measurement.

OBJECTIVE: Amputation-free survival (AFS), a composite endpoint of mortality and amputation, is the preferred outcome measure in critical limb ischemia (CLI). Given the improvements in systemic management of atherosclerosis and interventional management of limb ischemia over the past 2 decades, we examined whether these outcomes have changed in patients with CLI without revascularization options (no option-critical limb ischemia [NO-CLI]). METHODS: We reviewed the literature for published 1-year AFS, mortality, and amputation rates from control groups in NO-CLI trials. Summary proportions of events were estimated by conducting a random effects meta-analysis of proportions. To determine whether there had been any change in event rates over time, we performed a random effects meta-regression and a mixed effects logistic regression, both regressed against the variable "final year of recruitment." RESULTS: Eleven trials consisting of 886 patients satisfied search criteria, 7 of which presented AFS data. Summary proportion of events (95% confidence interval) were 0.551 (0.399 to 0.693) for AFS; 0.198 (0.116 to 0.317) for death; and 0.341 (0.209 to 0.487) for amputation. Regression analyses demonstrated that AFS has risen over time as mortality rates have fallen, and these improvements are statistically significant. The decrease in amputation rates failed to reach statistical significance. The lack of published data precluded a quantitative evaluation of any change in the clinical severity or comorbidities in the NO-CLI population. CONCLUSIONS: AFS and mortality rates in NO-CLI have improved over the past 2 decades. Due to declining event rates, clinical trials may underestimate treatment effects and thus fail to reach statistical significance unless sample sizes are increased or unless a subgroup with a higher event rate can be identified. Alternatively, comparing outcomes to historical values for quality measurement may overestimate treatment effects. Benchmark values of AFS and morality require periodic review and updating.

An Analysis of Guideline Consensus for the Prevention, Diagnosis, and Management of Diabetic Foot Ulcers.

BACKGROUND: Multiple organizations have issued guidelines to address the prevention, diagnosis, and management of diabetic foot ulcers (DFUs) based on evidence review and expert opinion. We reviewed these guidelines to identify consensus (or lack thereof) on the nature of these recommendations, the strength of the recommendations, and the level of evidence. METHODS: Ovid, PubMed, Web of Science, Cochrane Library, and Embase were searched in October 2018 using the MESH term diabetic foot, the key word diabetic foot, and the filters guideline or practice guideline. To minimize recommendations based on older literature, guidelines published before 2012 were excluded. Articles without recommendations characterized by strength of recommendation and level of evidence related specifically to DFU were also excluded. A manual search for societal recommendations yielded no further documents. Recommendations were ultimately extracted from 12 articles. Strength of evidence and strength of recommendation were noted for each guideline recommendation using the Grading of Recommendations Assessment, Development, and Evaluation system or the Centre for Evidence-Based Medicine system. To address disparate grading systems, we mapped the perceived level of evidence and strength of recommendations onto the American Heart Association guideline classification schema. RESULTS: Recommendations found in two or more guidelines were collected into a clinical checklist characterized by strength of evidence and strength of recommendation. Areas for future research were identified among recommendations based on minimal evidence, areas of controversy, or areas of clinical care without recommendations. CONCLUSIONS: Through this work we developed a multidisciplinary set of DFU guidelines stratified by strength of recommendation and quality of evidence, created a clinical checklist for busy practitioners, and identified areas for future focused research. This work should be of value to clinicians, guideline-issuing bodies, and researchers. We also formulated a method for the review and integration of guidelines issued by multiple professional bodies.

The American Venous Forum, American Vein and Lymphatic Society and the Society for Vascular Medicine expert opinion consensus on lymphedema diagnosis and treatment.

BACKGROUND: Lymphedema imposes a significant economic and social burden in modern societies. Controversies about its risk factors, diagnosis, and treatment permeate the literature. The goal of this study was to assess experts' opinions on the available literature on lymphedema while following the Delphi methodology. METHODS: In December of 2019, the American Venous Forum created a working group tasked to develop a consensus statement regarding current practices for the diagnosis and treatment of lymphedema. A panel of experts was identified by the working group. The working group then compiled a list of clinical questions, risk factors, diagnosis and evaluation, and treatment of lymphedema. Fifteen questions that met the criteria for consensus were included in the list. Using a modified Delphi methodology, six questions that received between 60% and 80% of the votes were included in the list for the second round of analysis. Consensus was reached whenever >70% agreement was achieved. RESULTS: The panel of experts reached consensus that cancer, infection, chronic venous disease, and surgery are risk factors for secondary lymphedema. Consensus was also reached that clinical examination is adequate for diagnosing lymphedema and that all patients with chronic venous insufficiency (C3-C6) should be treated as lymphedema patients. No consensus was reached regarding routine clinical practice use of radionuclide lymphoscintigraphy as a mandatory diagnostic tool. However, the panel came to consensus regarding the importance of quantifying edema in all patients (93.6% in favor). In terms of treatment, consensus was reached favoring the regular use of compression garments to reduce lymphedema progression (89.4% in favor, 10.6% against; mean score of 79), but the use of Velcro devices as the first line of compression therapy did not reach consensus (59.6% in favor vs 40.4% against; total score of 15). There was agreement that sequential pneumatic compression should be considered as adjuvant therapy in the maintenance phase of treatment (91.5% in favor vs. 8.5% against; mean score of 85), but less so in its initial phases (61.7% in favor vs. 38.3% against; mean score of 27). Most of the panel agreed that manual lymphatic drainage should be a mandatory treatment modality (70.2% in favor), but the panel was split in half regarding the proposal that reductive surgery should be considered for patients with failed conservative treatment. CONCLUSION: This consensus process demonstrated that lymphedema experts agree on the majority of the statements related to risk factors for lymphedema, and the diagnostic workup for lymphedema patients. Less agreement was demonstrated on statements related to treatment of lymphedema. This consensus suggests that variability in lymphedema care is high even among the experts. Developers of future practice guidelines for lymphedema should consider this information, especially in cases of low-level evidence that supports practice patterns with which the majority of experts disagree.

Relation of platelet and leukocyte inflammatory transcripts to body mass index in the Framingham heart study.

BACKGROUND: Although many genetic epidemiology and biomarker studies have been conducted to examine associations of genetic variants and circulating proteins with cardiovascular disease and risk factors, there has been little study of gene expression or transcriptomics. Quantitative differences in the abundance of transcripts has been demonstrated in malignancies, but gene expression from a large community-based cohort examining risk of cardiovascular disease has never been reported. METHODS AND RESULTS: On the basis of preliminary microarray data and previously suggested genes from the literature, we measured expression of 48 genes by high-throughput quantitative reverse-transcriptase polymerase chain reaction in 1846 participants of the Framingham Offspring cohort from RNA derived from isolated platelets and leukocytes. A multivariable stepwise regression model was used to assess clinical correlates of quantitative RNA expression. For specific inflammatory platelet-derived transcripts, including ICAM1, IFNG, IL1R1, IL6, MPO, COX2, TNF, TLR2, and TLR4, there were significant associations with higher body mass index (BMI). Compared with platelets, fewer leukocyte-derived transcripts were associated with BMI or other cardiovascular risk factors. Select transcripts were found to be highly heritable, including GPIBA and COX1. Almost uniformly, heritable transcripts were not those associated with BMI. CONCLUSIONS: Inflammatory transcripts derived from platelets, particularly those part of the nuclear factor kappa B pathway, are associated with BMI, whereas others are heritable. This is the first study, using a large community-based cohort, to demonstrate clinical correlates of gene expression and is consistent with the hypothesis that specific peripheral-blood transcripts play a role in the pathogenesis of coronary heart disease and its risk factors.

The role of amputation as an outcome measure in cellular therapy for critical limb ischemia: implications for clinical trial design.

BACKGROUND: Autologous bone marrow-derived stem cells have been ascribed an important therapeutic role in No-Option Critical limb Ischemia (NO-CLI). One primary endpoint for evaluating NO-CLI therapy is major amputation (AMP), which is usually combined with mortality for AMP-free survival (AFS). Only a trial which is double blinded can eliminate physician and patient bias as to the timing and reason for AMP. We examined factors influencing AMP in a prospective double-blinded pilot RCT (2:1 therapy to control) of 48 patients treated with site of service obtained bone marrow cells (BMAC) as well as a systematic review of the literature. METHODS: Cells were injected intramuscularly in the CLI limbs as either BMAC or placebo (peripheral blood). Six month AMP rates were compared between the two arms. Both patient and treating team were blinded of the assignment in follow-up examinations. A search of the literature identified 9 NO-CLI trials, the control arms of which were used to determine 6 month AMP rates and the influence of tissue loss. RESULTS: Fifteen amputations occurred during the 6 month period, 86.7% of these during the first 4 months. One amputation occurred in a Rutherford 4 patient. The difference in amputation rate between patients with rest pain (5.6%) and those with tissue loss (46.7%), irrespective of treatment group, was significant (p = 0.0029). In patients with tissue loss, treatment with BMAC demonstrated a lower amputation rate than placebo (39.1% vs. 71.4%, p = 0.1337). The Kaplan-Meier time to amputation was longer in the BMAC group than in the placebo group (p = 0.067). Projecting these results to a pivotal trial, a bootstrap simulation model showed significant difference in AFS between BMAC and placebo with a power of 95% for a sample size of 210 patients. Meta-analysis of the literature confirmed a difference in amputation rate between patients with tissue loss and rest pain. CONCLUSIONS: BMAC shows promise in improving AMP-free survival if the trends in this pilot study are validated in a larger pivotal trial. The difference in amp rate between Rutherford 4 & 5 patients suggests that these patients should be stratified in future RCTs.

The utility of screening for deep venous thrombosis in asymptomatic, non-ambulatory neurosurgical patients.

OBJECTIVES: Decisions regarding deep venous thrombosis (DVT) prophylaxis are complicated in neurosurgical patients because of the potential for catastrophic bleeding complications. Screening with venous duplex ultrasound (VDUS) may improve outcomes, but can strain hospital resources. Since there is little data to guide VDUS surveillance, we investigated the utility of a comprehensive VDUS screening program in neurosurgical patients. METHODS: Medical records of patients admitted to the neurosurgical service at a university-affiliated hospital from October 2007 through January 2010 who underwent weekly VDUS of the lower extremities until ambulatory or discharged were retrospectively reviewed. Demographics, comorbidities, interventions, and use of DVT prophylaxis were recorded. All patients in this study were asymptomatic for clinical evidence of DVT. When DVT was identified, VDUS reported its location and progression. RESULTS: One hundred seventy-four consecutive patients were screened according to the established protocol. They had 312 VDUS studies, 68 (21.8%) of which were positive in 40 (23%) unique patients; 10 were bilateral and two catheter-related. There were no documented pulmonary emboli in this series. Seventeen patients (37.7%) had isolated calf DVT, four of which were bilateral (totaling 21 thrombi), and 9 (20%) had coexistent thrombi in calf and proximal veins. Of the 21 isolated calf DVTs, 15 had follow-up studies and two progressed to the popliteal or ileofemoral vein on follow-up (13.3%). Mechanical prophylaxis was uniformly utilized, but chemical prophylaxis varied based on surgeons' assessment of bleeding risk. DVT developed in 19.3% (28/145) of patients receiving prophylactic medication (unfractionated heparin or low-molecular weight heparin) and 41.4% (12/29) receiving no chemoprophylaxis (P < .001). The only patient characteristic that correlated with DVT risk was a body mass index <30 (9.1% vs 29.4%, P = .01). CONCLUSIONS: Despite the uniform application of mechanical DVT prophylaxis and the use of chemoprophylaxis in a majority of patients, we found a 23% incidence of DVT in these hospitalized, nonambulatory, neurosurgical patients. No patients with isolated calf DVT had an embolic complication but 13.3% progressed proximally in short-term follow-up. While chemical prophylaxis significantly reduced DVT risk, no factor was sufficiently predictive to exclude patients from screening. These data substantiate the importance of full leg VDUS screening and maximizing DVT prophylaxis in this high risk population.