Activated Factor XI is Increased in Plasma in Response to Surgical Trauma but not to Recombinant Activated FVII-Induced Thrombin Formation.

AIM: Feedback activation of factor XI (FXI) by thrombin is believed to play a critical role in the amplification phase of thrombin generation and to contribute to thrombosis development and hemostasis. However, the activation of FXI by thrombin has been shown in vitro to require a cofactor. In this study, the role of thrombin in activated FXI (FXIa) formation in vivo is investigated. METHODS: The study population comprised probands in whom coagulation activation was triggered by low-dose (15 µg/kg) recombinant activated factor VII (rFVIIa, n=89), of whom 34 with (VTE+) and 45 without a history of venous thromboembolism (VTE-), and patients undergoing major orthopedic surgeries (n=45). FXIa was quantified via an enzyme capture assay using a monoclonal FXI-specific antibody. Thrombin formation was monitored using an oligonucleotide-based enzyme capture assay and the thrombin activation markers prothrombin fragment 1＋2 (F1＋2) and thrombin-antithrombin complex (TAT). RESULTS: In the rFVIIa cohort, FXIa and thrombin remained below their lower limit of quantification of 3.48 and 1.06 pmol/L, respectively. By contrast, during the surgeries, median FXIa levels increased from 3.69 pmol/L pre-operatively to 9.41 pmol/L mid-operatively (P=4·10-4) and remained significantly elevated 24 h thereafter, with 9.38 pmol/L (P=0.001). Peak levels of F1+2 were comparable in the VTE+, VTE-, and surgery cohort (235, 268, and 253 pmol/L), whereas peak TAT levels were higher in the surgery cohort (53.1, 33.9, and 147.6 pmol/L). CONCLUSIONS: Under in vivo conditions, the activation of FXI requires specific local features that are present at the wounded site including potential cofactors of thrombin.

Robust hemostatic bandages based on nanoclay electrospun membranes.

Death from acute hemorrhage is a major problem in military conflicts, traffic accidents, and surgical procedures, et al. Achieving rapid effective hemostasis for pre-hospital care is essential to save lives in massive bleeding. An ideal hemostasis material should have those features such as safe, efficient, convenient, economical, which remains challenging and most of them cannot be achieved at the same time. In this work, we report a rapid effective nanoclay-based hemostatic membranes with nanoclay particles incorporate into polyvinylpyrrolidone (PVP) electrospun fibers. The nanoclay electrospun membrane (NEM) with 60 wt% kaolinite (KEM1.5) shows better and faster hemostatic performance in vitro and in vivo with good biocompatibility compared with most other NEMs and clay-based hemostats, benefiting from its enriched hemostatic functional sites, robust fluffy framework, and hydrophilic surface. The robust hemostatic bandages based on nanoclay electrospun membrane is an effective candidate hemostat in practical application.

Adipocyte lipolysis drives acute stress-induced insulin resistance.

Stress hyperglycemia and insulin resistance are evolutionarily conserved metabolic adaptations to severe injury including major trauma, burns, or hemorrhagic shock (HS). In response to injury, the neuroendocrine system increases secretion of counterregulatory hormones that promote rapid mobilization of nutrient stores, impair insulin action, and ultimately cause hyperglycemia, a condition known to impair recovery from injury in the clinical setting. We investigated the contributions of adipocyte lipolysis to the metabolic response to acute stress. Both surgical injury with HS and counterregulatory hormone (epinephrine) infusion profoundly stimulated adipocyte lipolysis and simultaneously triggered insulin resistance and hyperglycemia. When lipolysis was inhibited, the stress-induced insulin resistance and hyperglycemia were largely abolished demonstrating an essential requirement for adipocyte lipolysis in promoting stress-induced insulin resistance. Interestingly, circulating non-esterified fatty acid levels did not increase with lipolysis or correlate with insulin resistance during acute stress. Instead, we show that impaired insulin sensitivity correlated with circulating levels of the adipokine resistin in a lipolysis-dependent manner. Our findings demonstrate the central importance of adipocyte lipolysis in the metabolic response to injury. This insight suggests new approaches to prevent insulin resistance and stress hyperglycemia in trauma and surgery patients and thereby improve outcomes.

Comparison of Postsurgical Scars Between Vegan and Omnivore Patients.

BACKGROUND: Postsurgical skin healing can result in different scars types, ranging from a fine line to pathologic scars, in relation to patients' intrinsic and extrinsic factors. Although the role of nutrition in influencing skin healing is known, no previous studies investigated if the vegan diet may affect postsurgical wounds. OBJECTIVE: The aim of this study was to compare surgical scars between omnivore and vegan patients. METHODS AND MATERIALS: This is a prospective observational study. Twenty-one omnivore and 21 vegan patients who underwent surgical excision of a nonmelanoma skin cancer were enrolled. Postsurgical complications and scar quality were evaluated using the modified Scar Cosmesis Assessment and Rating (SCAR) scale. RESULTS: Vegans showed a significantly lower mean serum iron level (p < .001) and vitamin B12 (p < .001). Wound diastasis was more frequent in vegans (p = .008). After 6 months, vegan patients had a higher modified SCAR score than omnivores (p < .001), showing the worst scar spread (p < .001), more frequent atrophic scars (p < .001), and worse overall impression (p < .001). CONCLUSION: This study suggests that a vegan diet may negatively influence the outcome of surgical scars.

Assessment of Silver Levels in a Closed-Incision Negative Pressure Therapy Dressing: In Vitro and In Vivo Study.

Objective: In recent years, reticulated open-cell foam-based closed-incision negative pressure therapy (ROCF-ciNPT) has shown effectiveness in management of various postoperative incisions. These dressings consist of a skin interface layer that absorbs fluid from the skin surface and reduces the potential for microbial colonization within the dressing by means of ionic silver. This study examines the ability of silver to reduce the bioburden within the dressing as well as the localized effect due to potential silver mobility. Approach: Ability of silver to reduce bioburden within the ROCF-ciNPT dressing was assessed using Staphylococcus aureus, Pseudomonas aeruginosa, and Candida spp. Furthermore, silver mobility was assessed using an in vitro skin model to study the zone of inhibition along with released silver quantification. Using a porcine model, diffusion of silver into blood and tissue was studied using emission spectrometry and histology. Results: Microbial growth in the ROCF-ciNPT dressing was significantly reduced (∼2.7-4.9 log reduction) compared to a silver-free negative control. No zone of inhibition was observed for microbial colonies for up to 7 days with minimal localized silver release (<5.5 ppm release). In vivo studies demonstrated no measurable concentration (<0.2 µg/g) of silver in the blood, urine, feces, kidney, and liver tissue biopsy. Innovation: This study provides an important insight into silver concentration and mobility within the ROCF-ciNPT dressing, given emerging concerns associated with potential silver cytotoxicity. Conclusion: These results indicate the concentration of silver (0.019% silver by weight) in the ROCF-ciNPT dressings has been adequate to reduce bioburden within the skin interface layer, while severely limiting the amount of silver leaching out.

Surgical wound-site inflammation: video-assisted thoracic surgery versus thoracotomy.

OBJECTIVES: Mechanical trauma occurring during pulmonary resection through both video-assisted thoracic surgery (VATS) or thoracotomy causes profound alterations in cytokines and the cellular network. The aim of this study was to analyse biological changes occurring in both the microenvironment (wound site) and macroenvironment (systemic circulation) following pulmonary lobectomy via the VATS or thoracotomic approach. METHODS: From October 2016 to July 2017, 30 patients with clinical Stage I lung cancer were recruited. In 12 cases (the VATS group), surgery was performed through a video-assisted thoracoscopic approach and in 15 cases (the thoracotomy group) through a muscle-sparing minithoracotomy. Following the skin incision, the wound was irrigated with a saline solution (20 ml) and then collected. After the pulmonary resection, the surgical incision was re-irrigated. The number of polymorphonuclears, granulocytes and lymphocytes in the fluids was determined by the fluorescence activated cell sorting (FACS) analysis. Cytokine profiles of interleukin (IL)-6, tumour necrosis factor (TNF)-α, IL-1 and IL-8 from sera and fluids were detected by the enzyme linked immunosorbent assay (ELISA) assay. Functional results were evaluated through spirometry, and pain was assessed using the visual analogue scale. RESULTS: In the postoperative fluids of the VATS group, fewer polymorphonuclears were seen compared to the thoracotomy group (P = 0.001), as well as a decreased percentage of granulocytes (P = 0.01) and a parallel increased lymphocytes fraction (P = 0.001). Only the systemic IL-1ß levels were significantly lower in postoperative sera of the VATS group (P = 0.038). No differences were observed regarding other cytokines. CONCLUSIONS: The local microenvironment during VATS differs from that of thoracotomy by not producing the same inflammatory phenotype. The clinical efficacy of a less invasive surgical approach is confirmed by a reduced inflammation of the systemic and local districts.

Tobacco exposure and wound healing in head and neck surgical wounds.

OBJECTIVE: Smoking impairs wound healing, yet the underlying pathophysiological mechanisms are unclear. We evaluated tobacco-altered healing in head and neck surgery by studying the association between biomarkers and tobacco exposure, as well as cutaneous perfusion by smoking status. STUDY DESIGN: Prospective cohort study, tertiary/academic care center, 2011 to present. METHODS: Patients who required head and neck surgery were enrolled prospectively. Postsurgical drain fluid was collected 24 hours postoperatively. Biomarkers associated with postulated mechanisms of smoking-impaired healing were assayed. These included interleukin-1, -6, and -8; tumor necrosis factor- alpha; transforming growth factor-beta; epidermal growth factor (EGF); basic fibroblastic growth factor (bFGF); C-reactive protein; vascular endothelial growth factor; soluble FMS-like tyrosine kinase-1 (sFLT-1); and placental growth factor. Tobacco exposure and clinical outcomes were recorded. Two sample two-sided t tests evaluated the differences in cytokine levels by tobacco exposure. In a second cohort, cutaneous vascular assessment via indocyanine green angiography was compared by smoking status. RESULTS: Twenty-eight patients were enrolled with drain fluid collection. Twenty-one subjects were current/former smokers, whereas seven were never smokers. EGF was higher in never smokers than smokers in a statistically significant manner (P = 0.030). Likewise, sFLT-1 was significantly higher in never smokers (P = 0.011). Cutaneous angiography revealed nonsmokers to have significantly higher cutaneous perfusion than smokers. CONCLUSION: In this head and neck surgical cohort, significantly higher EGF and sFLT-1 levels in wound fluid were associated with never smoking, suggesting that smoking has adverse effects on the inflammatory phase of wound healing. Cutaneous angiography supports the detrimental effect of smoking on skin perfusion. These findings suggest the need for further study as well as therapeutic targets for smokers undergoing surgery. LEVEL OF EVIDENCE: 2b. Laryngoscope, 128:618-625, 2018.

Ropivacaine, Interleukin-6 and Tumor Necrosis Factor Alpha Plasma Levels during Intermittent Epidural and Continuous Wound Infusion of Ropivacaine for Analgesia after Hysterectomy or Myomectomy: An Observational Study.

BACKGROUND/AIMS: The concentration-time profile of the long-acting local anesthetic ropivacaine after epidural (EP) administration at fixed time intervals or continuous subcutaneous (SC) infusion has not been fully evaluated. The objective of this work was to determine total plasma concentrations of ropivacaine and changes in cytokine interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) levels during EP and SC. METHODS: In this prospective randomized controlled trial, 18 patients undergoing abdominal hysterectomy or myomectomy were randomly selected to receive ropivacaine either every 6 h via an EP catheter or by continuous wound infusion along the skin incision, after a bolus dose, for 48 h. Total plasma ropivacaine concentrations were measured before the bolus and 2, 4, 8, 24, 48, and 50 h after the bolus using high-performance liquid chromatography-UV and IL-6 and TNF-α levels were measured at 0, 8 and 24 h with ELISA and analyzed statistically. RESULTS: During EP, mean ± SD ropivacaine concentrations were relatively stable up to 50 h postoperatively, that is, 239 ± 89 ng/ml, while during SC, initial concentrations between 2 and 8 h were comparatively lower (101.5 ± 42.9 ng/ml) than 24-50 h concentrations (437.1 ± 206 ng/ml). An increase in IL-6 levels was noted between 0 and 24 h during EP and SC, but TNF-α levels increased slightly, between 0 and 24 h, only during EP. CONCLUSION: Ropivacaine plasma concentrations with both EP and SC were found to be safe throughout the administration time interval. IL-6 levels increased during the same time interval, while TNF levels varied only slightly.

Presepsin as a predictor of critical colonization in CLI hemodialysis patients.

Infection during critical limb ischemia (CLI) is a challenging issue. Plasma presepsin is a novel biomarker for infection, which is related to bacterial phagocytosis by macrophages. The purpose of this study was to investigate the validity of presepsin as an indicator and predictor for early detection of infectious CLI. A retrospective observational study was conducted among 20 CLI patients (Rutherford 5 and 6) on hemodialysis (HD). Twenty CLI patients on HD (mean age 70.7 ± 5.6 years, male 85%) and 15 healthy patients on HD without CLI and infection (control group) were analyzed. All CLI patients received appropriate revascularization and plastic surgical treatment. CLI patients were classified into two groups: the healing group with complete epithelialization without discharge and the nonhealing group with infection signs. Plasma presepsin was measured and compared among the two groups and the control group using an automated immunoanalyzer, PATHFAST, based on a noncompetitive chemiluminescent enzyme immunoassay. The median plasma presepsin and its interquartile range were 1,320 (1,055-1,465) pg/mL in the control group, 1,320 (1,050-1,613) pg/mL in the healing group and 3,193 (2,519-3,832) pg/mL in the nonhealing group. The plasma presepsin concentrations were significantly higher in the nonhealing group compared with the control group (p < 0.001) and the healing group (p < 0.01). A receiver operating characteristic curve analysis revealed that presepsin had highest accuracy (0.979) among various inflammatory markers, including C-reactive protein and the white blood cell count. The diagnostic cutoff value of 2,083 pg/mL was able to distinguish the nonhealing group and healing group with a sensitivity of 100% and a specificity of 88.9%. Our results suggest that plasma presepsin may be useful for predicting "critical colonization" and "infection" in nonhealing CLI in HD patients, therefore, the definitive cutoff value may be used for determinating the indication for reintervention and/or major limb amputation.