Outcomes After Vascular Surgery Procedures in Patients with COVID-19 Infection: A National Multicenter Cohort Study (COVID-VAS).

OBJECTIVES: To analyze the outcome of vascular procedures performed in patients with COVID-19 infection during the 2020 pandemic. METHODS: This is a multicenter, prospective observational cohort study. We analyzed data from 75 patients with COVID-19 infection undergoing vascular surgery procedures in 17 hospitals across Spain and Andorra between March and May 2020. The primary end point was 30-day mortality. Clinical Trials registry number NCT04333693. RESULTS: The mean age was 70.9 (45-94) and 58 (77.0%) patients were male. Around 70.7% had postoperative complications, 36.0% of patients experienced respiratory failure, 22.7% acute renal failure, and 22.7% acute respiratory distress syndrome (ARDS). All-cause 30-days mortality rate was 37.3%. Multivariate analysis identified age >65 years (P = 0.009), American Society of Anesthesiologists (ASA) classification IV (P = 0.004), preoperative lymphocyte count <0.6 (×109/L) (P = 0.001) and lactate dehydrogenase (LDH) >500 (UI/L) (P = 0.004), need for invasive ventilation (P = 0.043), postoperative acute renal failure (P = 0.001), ARDS (P = 0.003) and major amputation (P = 0.009) as independent variables associated with mortality. Preoperative coma (P = 0.001), quick Sepsis Related Organ Failure Assessment (qSOFA) score ≥2 (P = 0.043), lymphocytes <0.6 (×109/L) (P = 0.019) leucocytes >11.5 (×109/L) (P = 0.007) and serum ferritin >1800 mg/dL (P = 0.004), bilateral lung infiltrates on thorax computed tomography (P = 0.025), and postoperative acute renal failure (P = 0.009) increased the risk of postoperative ARDS. qSOFA score ≥2 was the only risk factor associated with postoperative sepsis (P = 0.041). CONCLUSIONS: Patients with COVID-19 infection undergoing vascular surgery procedures showed poor 30-days survival. Age >65 years, preoperative lymphocytes <0.6 (x109/L) and LDH >500 (UI/L), and postoperative acute renal failure, ARDS and need for major amputation were identified as prognostic factors of 30-days mortality.

Meta-analysis and adjusted indirect comparison of direct oral anticoagulants in prevention of acute limb ischemia in patients with atrial fibrillation.

BACKGROUND: Direct oral anticoagulants are being presented as alternatives to warfarin for preventing stroke in patients with atrial fibrillation. Yet direct comparative trials between these agents in prevention of acute limb ischemia (ALI) are unavailable so far. OBJECTIVE: To conduct an adjusted indirect comparison meta-analysis between direct oral agents for prevention of acute limb ischemia in atrial fibrillation. METHODS: We conducted a systematic literature review searching electronic databases (MEDLINE and Embase) and the Cochrane Library from January 1990 through November 2014. Two blinded investigators reviewed all potentially relevant articles in a parallel manner by using a priori defined criteria. To assess the long-term efficacy and safety of these agents, only randomized clinical trials (RCTs) with follow-up durations of >1 year were included. The primary efficacy outcome was the end point of acute limb ischemia and/or extremity embolism. RESULTS: A total of 44,563 patients from three RCTs met criteria for inclusion. Patients randomized to direct oral anticoagulants had a non-significant decreased risk for acute limb ischemia (risk ratio [RR]: 0.57, 95% confidence interval [CI]: 0.26-1.2). In the analysis between agents, however, rivaroxaban significantly lowered the risk of ALI compared to warfarin (RR: 0.23, 95% CI: 0.064-0.82), apixaban (RR: 0.26, 95% CI: 0.081-0.83), and dabigatran (RR: 0.24, 95% CI: 0.077-0.83). CONCLUSIONS: Significant differences in prevention of acute limb ischemia may exist between oral anticoagulant agents in patients with atrial fibrillation. Rivaroxaban lowers the risk of limb embolism versus warfarin, apixaban and dabigatran.

Analysis of vascular endothelial growth factor gene expression in the tissues of patients with chronic venous insufficiency.

OBJECTIVE: Immunohistochemical techniques have revealed the presence of vascular endothelial growth factor (VEGF) in the epidermis of patients with chronic venous disease (CVD). Our objective was to perform a quantitative analysis of the VEGF gene transcription in tissues that are potential sources of this factor (skin, varicose veins [VV] and great saphenous vein [GSV]) in patients with CVD. METHODS: In all, 212 skin and venous tissue samples were collected from patients diagnosed with CVD and controls. The VEGF gene expression was analysed using quantitative realtime polymerase chain reaction (PCR). RESULTS: The skin VEGF expression was lower in the CVD group than in the control group (P = 0.04). There were no significant differences between the insufficient GSV of the CVD group and the control healthy vein (P = 0.22). There was a greater expression of VEGF in the VV of the CVD group than in the control healthy vein (P = 0.03). Comparison of the VEGF expression between the different tissue types in the CVD group revealed significant differences between the skin and GSV (P = 0.02) and between the skin and the VV (P = 0.004), and between the VV and the GSV (P = 0.02). CONCLUSIONS: The results of the present study show an over-expression of VEGF gene in the VV tissue of patients with CVD. Based on the data in patients with C2 disease, the VVs appear to be the source of increased VEGF expression.

Influence of surgical or endovascular distal revascularization of the lower limbs on ischemic ulcer healing.

AIM: Our aim is to analyze the ability of distal endovascular procedures, performed as first treatment option, to promote ischemic ulcer healing. METHODS: Retrospective analysis of 91 primary distal procedures, 49 (53.8%) surgical and 42 (46.2%) endovascular, performed consecutively between January 2005 and December 2007 in patients with critical limb ischemia (CLI) and ischemic ulcers. Patient comorbidities, intervention duration time, postoperative hospital stay and complications were recorded. Ischemic ulcer healing time, patency, limb salvage and survival rates were compared between both groups. Data were included in a Cox regression model to determine predictive factors for healing RESULTS: Endovascular therapy was associated with shorter intervention time (128±53 versus 301±91 min; P=0.001) and postoperative hospital stay (13±13 versus 19±14 days; P=0.05). Surgical procedures were associated with more local complications (28.6% versus 7.1% P=0.01), more readmissions for surgical wound complications (12.2% versus 0% P=0.03) and more early major amputations (16.3% versus 0% P=0.007). Ischemic ulcer healing in endovascular and surgical procedures was 80% versus 83% at 12 months (P=NS). Overall patency, limb salvage, survival and amputation-free survival with healed ulcers at 24 months in endovascular and surgical groups were 82% versus 82% (P=NS), 83% versus 72% (P=NS), 81% versus 79% (P=NS) and 63% versus 56% (P=NS). Diabetes mellitus (HR: 2.86 95% CI [1.44-5.68]), free ambulatory status (HR: 0.57 95% CI [0.33-0.98]) and the presence of severe wounds (HR: 2.73 95% CI [1.40-5.30]) were predictors for ulcer healing. CONCLUSION: Endovascular and surgical distal procedures had a similar ulcer healing rate and limb salvage. Our experience supports endovascular-first strategy for CLI with tissue loss.

Long-term pleiotropic effect of statins upon nitric oxide and C-reactive protein levels in patients with peripheral arterial disease.

OBJECTIVES: Peripheral arterial disease can be regarded as a systemic inflammatory disorder affecting the entire vascular system. In the early clinical stages, it is characterised by the deterioration of endothelial function, which does not progress with the development of the disease. This study analyses the pleiotropic effects upon the plasma nitrite and C-reactive protein (CRP) levels in claudicating patients after 12 months of treatment with statins. STUDY DESIGN: A prospective randomised controlled translational study was made in patients with Fontaine grade II ischaemia, treated with the best medical treatment with or without statins for 12 months from the time of diagnosis for assessing the pleiotropic effects of those statins. METHODS: Measurements of plasma high-sensitivity CRP (hsCRP), lipid profile and nitrites were made at baseline and after 1 month and 1 year of treatment with atorvastatin 40 mg/day. RESULTS: A significant reduction in nitrite levels was observed after 1 month of treatment (11.8±7.8 µM vs 5.7±1.8 µM, p=0.0001), but this effect did not persist after 1 year (11.8±7.8 µM vs 9.4±8.9 µM, p=0.27). HsCRP underwent a significant reduction after both 1 month (7 (2.2-12) vs 3.4 (1.6-5.5), p<0.01) and 1 year of treatment with atorvastatin (7 (2.2-12) vs 2.25 (1.67-6.7), p=0.02). Statin treatment reduced hsCRP levels in 9.64 (95% CI (1.60 to 17.68)) after 1 month and in 9.14 (95% CI (0.18 to 18.47)) after 1 year. CONCLUSIONS: The long-term biological pleiotropic effects of statins provide information on the role of endothelial function and systemic inflammation in the aetiopathogenesis of peripheral arterial disease. Statins slow endothelial degradation at the start of the disease, with no effects over the long term. These drug substances reduce progressive inflammation throughout the treatment period. This supports the novel hypothesis that endothelial dysfunction is only a disease-triggering phenomenon, while systemic inflammation would be responsible for both the origin and the maintenance of peripheral arterial disease.

Smell training increases cognitive smell skills of wine tasters compared to the general healthy population. The WINECAT Study.

BACKGROUND: Wine experts show higher accuracy than novices in selecting a wine that matches a sample. Only one study has compared wine experts with non-trained healthy controls on smell. The aim of this study was to compare the smell characteristics, both sensorial and cognitive, of wine tasters with Spanish healthy population using the Barcelona Smell Test-24. METHODS: Wine tasters were tested for smell and compared with a control group of healthy volunteers, by tasting 20 odours and scoring smell detection, identification, intensity, irritability, freshness, pleasure and forced choice. RESULTS: Wine tasters performed significantly better on identification and forced choice than healthy controls. In addition, wine tasters perceived more odours as intense, but fewer as irritating than controls. CONCLUSIONS: Probably linked to smell education, wine tasters show better cognitive but not sensorial smell skills than a non-trained healthy population.

[Smell disorders as early diagnosis in the early stage of sinonasal polyposis]. / Alteraciones olfativas como diagnóstico precoz de la poliposis nasosinusal incipiente.

INTRODUCTION: The increasing demand for attention to olfactory disorders, along with the persistent presence of sinonasal polyposis, has opened the need to treat these pathologies in very early stages. OBJECTIVES: To demonstrate that incipient stages in sinonasal polyposis are detectable by olfactometry before radiological images, and that this detection is linked with a non-blocked area around the nasal meatus (where the olfactory cleft is located). METHODS: This study is based on data obtained from a sinonasal polyposis (degree 0 or 1) patient group (n=121) without allergies or asthma backgrounds. The patients underwent both fibroscopic and olfactometry explorations (first and fifth cranial nerve) and computed axial tomography (CT) assessment. The results were compared with the control group (n=120). RESULTS: Significant values (p<0.05) of affectation were found in decreasing olfactory levels (olfactory and trigeminal nerves) in patients with degree 0 or 1 polyposis. CONCLUSION: Olfactory disorders linked to a non-blocked area around the nasal meatus (degree 1 or 2 polyposis), together with sinonasal CT scans showing beginnings of ethmoidal inflammation, should be interpreted as incipient sinonasal polyposis.

Direct association between C-reactive protein serum levels and endothelial dysfunction in patients with claudication.

OBJECTIVES: To evaluate the relationship between C-Reactive Protein (hsCRP), a serum marker of inflammation, and endothelial dysfunction in patients with intermittent claudication. DESIGN, PATIENTS AND METHODS: Cross-sectional study with stratified sampling on dependent variables of age, genre, hypertension, hyperlipidemia, diabetes, smoking status and ankle-brachial index (ABI) to select 156 patients from a target population of 4,100 patients with claudication. We assessed the flow-mediated arterial dilation (FMAD) as a reporter of endothelial function and plasma levels of hsCRP and fibrinogen. RESULTS: Patients with a FMAD<3% (range for the lowest 5% of healthy subjects) had increased levels of plasma hsCRP (6.3 vs 2.3mg/L; p<0.05) and fibrinogen (351vs 302mg/L; p<0.05) in comparison to those with FMAD>3%. There was a negative correlation between hsCRP and FMAD(r=-0.465; p<0.05). CONCLUSION: Impaired endothelial dysfunction is association with increased plasma concentrations of inflammatory markers, and both may have a role in the aetiopathogenesis of peripheral arterial disease.

Effects of topical glucocorticoids on in vitro lactoferrin glandular secretion: comparison between human upper and lower airways.

BACKGROUND: Mucus hypersecretion is a hallmark of upper and lower airway diseases, such as rhinitis, asthma, and chronic obstructive pulmonary disease. Although topical glucocorticoids are widely used to treat mucosal inflammation, their effect on mucus hypersecretion remains uncertain. OBJECTIVE: The aim of this study was to investigate the effect of budesonide and beclomethasone dipropionate on in vitro lactoferrin glandular secretion from both human nasal and bronchial mucosa and the potential mediating role of lipocortin 1. METHODS: Nasal and bronchial explants obtained from patients undergoing surgery were cultured in a controlled atmosphere. Lactoferrin (ELISA) was measured in culture supernatants, and lipocortin 1 (Western blot) was analyzed in explant tissues. RESULTS: Both budesonide and beclomethasone dipropionate (10(-6) mol/L) decreased spontaneous lactoferrin secretion in nasal and bronchial mucosa. The maximum effect of cortico-steroids (10(-6) mol/L) was obtained at day 3 in bronchial mucosa (budesonide: -56% +/- 9%, P <.05; beclomethasone dipropionate: -32% +/- 6%, P <.05) and at day 5 in nasal mucosa (budesonide: -34% +/- 10%, P <.05; beclomethasone dipropionate: -37% +/- 10%, P <.05). Methacholine (10(-4) mol/L) increased lactoferrin secretion in both bronchial (248% +/- 72%, P <.05) and nasal (107% +/- 28%, P <.05) explants, with this effect being completely abrogated by atropine. Budesonide caused a dose-related inhibitory effect on methacholine-induced lactoferrin secretion that was similar in both bronchial (down to -86% at 10(-6) mol/L) and nasal (down to -73% at 10(-6) mol/L) mucosa. Budesonide (10(-6) mol/L) did not show any effect on lipocortin 1 expression. CONCLUSIONS: These results suggest that glucocorticoid effects on airway inflammation may include a reduction of mucus hypersecretion in both nasal and bronchial mucosa.

Mesothelial versus endothelial cell seeding: evaluation of cell adherence to a fibroblastic matrix using 111In oxine.

OBJECTIVES: The aim of this study was to compare the behaviour of mesothelial cells (MC) to that of endothelial cells (EC) when seeded onto a PTFE, prosthesis coated with a fibroblastic matrix. DESIGN, MATERIAL AND METHODS: Three study groups were examined: a control group (Control) of PTFE prostheses with a fibroblast matrix (n = 8); Group EC, PTFE prostheses seeded with EC on a fibroblastic matrix (n = 8); and Group MC, PTFE, prostheses seeded with MC on a fibroblastic matrix (n = 8). All cell types were labelled with 111In (100 microCi/ml) 24 h after seeding, when the cells had formed a monolayer on the prosthetic surface. Radioactive levels were measured at 2, 4, 6, and 24 h. RESULTS: Both EC and MC showed optimal adherence. The MC had a better radioactive uptake and retention than the EC. The number of EC and MC cells that remained adherent to the matrix was large enough to ensure complete covering of the prosthetic surface. CONCLUSION: The use of MC is therefore feasible as an optimal alternative for achieving a natural covering on vascular prostheses prepared with a fibroblastic matrix.

Antithrombotic map of the N-terminal domain of the GPIIIa subunit of the human platelet fibrinogen receptor (GPIIb-IIIa) determined in vivo by monoclonal, immunochemical inhibition of acute arterial thrombosis.

The inhibition of the platelet fibrinogen receptor, the glycoprotein IIb-IIIa (GPIIb-IIIa) or integrin alphaIIbbeta3, has recently became an accepted practice in clinical cardiology. The interest lies now in the improvement of the antithrombotic activity and the minimization of the secondary effects of the receptor inhibitors, by their evaluation in vivo in the different dynamic conditions and pathological states under which these inhibitors have to perform. In this paper, we functionally map in vivo the N-terminal domain of the GPIIIa subunit, using the antithrombotic activity of five murine monoclonal antibodies (mabs) (P37, P40, 95-1, P95-2 and P97), all of them inhibitors of platelet aggregation in vitro and directed to this ligand binding domain of the human fibrinogen receptor. Competition experiments have shown that these mabs bind with high affinity (5-7 nM) and compete very strongly among themselves for binding to human resting platelets, except P40, which neither binds nor competes. These antibodies were assayed in a dog model of acute thrombosis in the carotid artery, which were induced 15 min after their intravenous administration (0.8 mg/kg). The antithrombotic activity was quantified by the measurement of the [111In]oxine-labelled platelet deposition at the site of the arterial lesion and was expressed as the percentage of the total circulating platelets. Antibody P37, directed to the GPIIIa 101-109 sequence, decreased the platelet deposition 630-fold with respect to control animals. P95-2, P97 and P95-1 decreased the platelet deposition 160-, 32- and 25-fold, respectively, while P40, directed to the GPIIIa 260-302 sequence, did not show any antithrombotic activity. We conclude that all the mabs directed to the N-terminal domain of GPIIIa, which inhibit platelet aggregation in vitro and whose epitopes are very close to each other and exposed in resting platelets, have high antithrombotic activity in vivo, which varies depending on the actual location of the epitopes in the receptor topography. Among these antibodies, P37, the strongest receptor inhibitor in vivo and whose epitope is most probably the closest to the fibrinogen binding site(s), seems the best candidate for comparative studies in animal models with today's best GPIIb-IIIa inhibitors and for clinical trials in humans in order to arrest or prevent thrombosis, reocclusion and late restenosis.

Experimental study of the antithrombogenic behavior of Dacron vascular grafts coated with hydrophilic acrylic copolymers bearing salicylic acid residues.

The objective of the present work was study of the behavior of active coatings of hydrophilic acrylic polymers bearing salicylic acid residues linked covalently to the macromolecular chains, after their application to woven and knitted Dacron vascular grafts. In vitro tests were carried out under dynamic flow conditions using equipment especially designed to reproduce physiologic conditions, to determine the retention of the coating using a saline solution. Ex vivo tests were carried out in an extracorporeal circuit using the dog as an animal model. The study of the deposition of platelets was followed by labeling of autologous platelets with 111In-oxine, as well as by analysis of the surfaces of the prostheses by scanning electron microscopy. An application of thin coatings of hydrophilic acrylic copolymers improves the antithrombogenicity of the vascular grafts with respect to the uncoated prosthesis. The presence of relatively small amounts of units bearing salicylic acid residues in the copolymer chains (5-20 wt %) gives good results when they are applied to woven and knitten Dacron meshes which have been quantified by analysis of the percentage of radiotracer on the surface of the vascular grafts tested in ex vivo experiments. The salicylic acid residues are released slowly to the medium by hydrolysis of the reversible covalent bonds of this compound to the acrylic macromolecular chains, which provides an additional antiaggregating effect for platelets. The polymeric coating forms a thin active film which improves the antithrombogenic properties of the surface of woven or knitted Dacron vascular grafts in ex vivo experiments.

Perineural spread of cutaneous squamous cell carcinoma manifesting as ptosis and ophthalmoplegia (orbital apex syndrome).

This paper reports two cases of orbital apex syndrome. The most salient clinical signs, ophthalmoplegia and eyelid ptosis, arose from perineural spread of facial squamous cell carcinomas that were previously excised with tumour-free surgical margins and exhibited no signs of local or other regional recurrence. The interest of these two cases lies in the fairly rare occurrence of this type of tumour spread and the highly aggressive nature of the tumour, unequivocal diagnosis of which usually arrives too late for a surgical solution. Awareness of the possibility of such perineural spread may allow the clinician to establish an early diagnosis and thus undertake radical surgery, thereby increasing the likelihood of success in combination with postoperative radiotherapy.

Application of new coatings for vascular grafts based on polyacrylic systems with antiaggregating activity.

A study has been made of the behaviour of knitted and woven Dacron mesh used in the preparation of vascular grafts when coated with either a layer of poly(2-hydroxyethyl methacrylate) or co-polymers of 2-hydroxyethyl methacrylate with 5, 10 or 20 wt% of an acrylic derivative of salicylic acid, 2-methacryloyloxybenzoic acid. In vitro studies were carried out to quantify the loss of polymer under flow conditions, and ex vivo studies were done in dogs to quantify the deposition of 111In-oxine-labelled platelets. The treated materials showed a lesser deposition of platelet thrombi when compared with the control group.

Prevention of arterial thrombosis by a monoclonal antibody against the 100 to 109 amino acid sequence stretch of the beta-subunit of the human platelet fibrinogen receptor: a comparative study with low dose aspirin.

OBJECTIVES: The aim of this study was to compare, in dogs, the antithrombotic activity of aspirin and the murine monoclonal antibody P37, which inhibits platelet aggregation and fibrinogen binding to activated platelets. BACKGROUND: The antithrombotic activity of P37 has been somewhat predictable, given its in vitro platelet antiaggregating activity and localization at or very near the fibrinogen binding site in the platelet fibrinogen receptor, the glycoprotein IIb/IIIa or integrin alpha IIb-beta 3. METHODS: The monoclonal antibody P37 of the immunogamma-globulin-1 isotype was prepared according to previously described immunization and fusion protocols and screening assays. To compare its antiaggregating capacity with that of aspirin, experimental thrombosis was induced in all dogs by means of direct current applied to the carotid artery. Autologous platelets had previously been labeled with indium-111 oxine. The dogs were assigned to three groups: group I (n = 18) was the control group; group II (n = 12) was treated orally with 5 mg of aspirin/kg body weight per day for 7 days before induction of thrombosis, and group III (n = 10) was treated intravenously with a single dose of P37 (0.8 mg/kg). RESULTS: The indium-111 oxine activity deposited in the thrombi was 12.94 +/- 12.83% (mean +/- SD) in group I, 3.55 +/- 2.99% in group II and 0.03 +/- 0.03% in group III. The differences between groups were always statistically significant (p < 0.05). CONCLUSIONS: We conclude that a single dose (0.8 mg/kg) of P37 in a canine model of arterial thrombosis is approximately 100 times more efficient than the administration of aspirin (5 mg/kg per day) in preventing platelet deposition during thrombus formation.

Prevention of thrombus formation on biomaterials exposed to blood using different antiplatelet drugs: experimental study in dogs.

An ex vivo shunt, established in dogs between both femoral arteries and right atrium, has been used to quantify the platelet deposition on six prosthetic materials used in the construction of cardiovascular prostheses: highly porous knitted Dacron (intervascular HP 800, 1400 mL/cm2/min/120 mm Hg), low-porosity woven Dacron (intervascular LP 200, 200 mL/cm2/min/120 mm Hg), double velour knitted Dacron, Avcothane 51 elastomere, and the mesothelial and epipericardial surfaces of bovine pericardium. In the search for a method to prevent platelet thrombi formation on these materials, we studied four groups of dogs: group 1 (control), group 2 (5 mg/kg body weight (BW)/day acetylsalicylic acid), group 3 (20 mg/kg BW/day acetylsalicylic acid), and group 4 (5 mg/kg BW/day acetylsalicylic acid plus 5 mg/kg BW/day dipyridamole). Platelets were labeled with 111In-oxine. The least thrombogenic material was Avcothane 51 elastomere. The only effective treatment for reduction of platelet deposition on the six materials was 5 mg/kg BW/day of acetylsalicylic acid. The dose used in group 3 only decreased the deposition of platelets on three of the six materials studied. The treatment employed in group 4 did not significantly reduce the deposition of platelets on any of the materials when compared with the control group.