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.

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.

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.

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.

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.

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.

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.

Prognostic value of the CD4/CD8 lymphocyte ratio in moderately burned patients.

We investigated CD3+, CD4+ and CD8+ T-cell subpopulations, as well as the CD4/CD8 ratio in 84 moderately burned patients with injuries affecting 11-36 per cent of their total body surface area (TBSA). These lymphocyte subpopulations were quantified by indirect immunofluorescence measurement 7 and 60 days postburn. The results obtained 7 days postburn were highly significant in those patients who developed septicaemia, all of whom had considerably decreased CD4+ and increased CD8+ T-cell numbers, as well as inverted CD4/CD8 ratios. Consequently, the CD4/CD8 ratio may provide valuable information for prognosis of patient evolution and the establishment of early treatment in order to avoid likely future complications.

Incidence of ember burns in Andalusia (Spain).

A 6-year analysis of 2000 cases of burns was carried out. Half of the patients were from rural and the other half from urban locations. One hundred and sixty-two patients out of the 2000 suffered from ember burns. The number of rural patients affected was greater than urban patients (117 vs. 45). Ember burns are frequent in Andalusia and have severe aesthetic and functional sequelae. Burns of this type are more common in children than in adults, so they carry an added social and medical relevance.

[Use of aspirin in the primary prevention of vascular thrombi. A comparative study with other anti-aggregant drugs]. / Utilización de la aspirina en la prevención primaria de trombos vasculares. Estudio comparativo con otros fármacos antiagregantes.

We have induced the formation of arterial (carotid) and venous (femoral) thrombi in dogs by means of an intima lesion produced by continuous current. The platelets were labeled with 111In oxine. Groups of 7 mongrel dogs received treatment for 7 days prior to the trial: group I, control; group II, 5 mg/kg body weight/day acetylsalicylic acid; group III, 20 mg/kg body weight/day acetylsalicylic acid; group IV, 15 mg/kg body weight/day triflusal + 5 mg/kg body weight/day dipyridamole; group V, 15 mg/kg body weight/day triflusal; and group VI, 5 mg/kg body weight/day acetylsalicylic acid + 5 mg/kg body weight/day dipyridamole. The only effective treatment for arterial thrombosis prevention was that employed in group II (p less than 0.05). Venous thrombosis was prevented in groups II (p less than 0.01), III (p less than 0.01) and VI (p less than 0.01).

[Thrombosis from prosthetic materials: prevention with different antiaggregatory agents. Low dose aspirin?]. / Trombosis sobre materiales protésicos: prevención con distintos fármacos antiagregantes. Aspirina a dosis bajas?

Using an ex vivo shunt in dogs, platelet deposition on 6 prosthetic materials used in the construction of cardiovascular prostheses [highly porous Knitted Dacron (intervascular HP 800, 1,400 ml/cm2/min/120 mmHg), Woven Dacron of low porosity (intervascular LP 200, 200 ml/cm2/min/120 mmHg), Doble Velour Knitted Dacron, Avcothane 51 elastomere and the mesothelial and epipericardial surfaces of bovine pericardium] was quantified. The study of the prevention of platelet thrombi formation on these materials was carried out in 6 groups of 8 animals: group 1 (control), group 2 (5 mg/kg body weight/day acetylsalicylic acid), group 3 (20 mg/kg body weight/day acetylsalicylic acid), group 4 (15 mg/kg body wt/day triflusal plus 5 mg/kg body wt/day dipyridamole), group 5 (15 mg/kg body wt/day triflusal) and group 6 (5 mg/kg body wt/day acetylsalicylic acid plus 5 mg/kg body wt/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 6 materials was that used in group 2. The treatment used in group 3 only decreased the deposition of platelets on 3 of the 6 materials. The treatments employed in groups 4, 5 and 6 did not significantly diminish the deposition of platelets on any of the materials when compared with the control group. The platelet count was not modified in the animals in groups 2 and 4 while in the rest it decreased after the test.

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.

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 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.

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.

Intrathecal injection of autologous leucocytes in glioblastoma: circulatory dynamics within the subarachnoid space and clinical results.

In part I of this report, the CSF circulatory dynamics of autologous leucocytes labelled with indium-111 and injected in the subarachnoid space, in patients operated on for glioblastoma, were studied. In the Part II, a series of 11 patients with recurrent glioblastoma was studied for evaluating the efficacy of intrathecal injection of autologous leucocytes. Six patients previously had radiotherapy. The results in Part I show that after intrathecal injection of autologous leucocytes, these cells follow throughout the subarachnoid space and pass to the systemic blood circulation, showing no evidence of colonization of the tumour or deposit in the tumoural region. The mean survival of the patients studied in Part II was 8 months. Those six patients who received radiotherapy had a mean survival of 11.4 months, and those five who received only intrathecal injection of autologous leucocytes after surgery, had a mean survival of 4 months. This results seem to demonstrate that immunotherapy, as used in this study, is ineffective in patients with glioblastoma.