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C3G is a Rap1 guanine nucleotide exchange factor that controls platelet activation, aggregation, and the release of α-granule content. Transgenic expression of C3G in platelets produces a net proangiogenic secretome through the retention of thrombospondin-1. In a physiological context, C3G also promotes megakaryocyte maturation and proplatelet formation, but without affecting mature platelet production. The aim of this work is to investigate whether C3G is involved in pathological megakaryopoiesis, as well as its specific role in platelet mediated angiogenesis and tumor metastasis. Using megakaryocyte-specific C3G knockout and transgenic mouse models, we found that both C3G overexpression and deletion promoted platelet-mediated angiogenesis, induced by tumor cell implantation or hindlimb ischemia, through differential release of proangiogenic and antiangiogenic factors. However, only C3G deletion resulted in a higher recruitment of hemangiocytes from the bone marrow. In addition, C3G null expression enhanced thrombopoietin (TPO)-induced platelet production, associated with reduced TPO plasma levels. Moreover, after 5-fluorouracil-induced platelet depletion and rebound, C3G knockout mice showed a defective return to homeostatic platelet levels, indicating impaired platelet turnover. Mechanistically, C3G promotes c-Mpl ubiquitination by inducing Src-mediated c-Cbl phosphorylation and participates in c-Mpl degradation via the proteasome and lysosome systems, affecting TPO internalization. We also unveiled a positive role of platelet C3G in tumor cell-induced platelet aggregation, which facilitated metastatic cell homing and adhesion. Overall, these findings revealed that C3G plays a crucial role in platelet-mediated angiogenesis and metastasis, as well as in platelet level modulation in response to pathogenic stimuli., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Hernández-Cano, Fernández-Infante, Herranz, Berrocal, Lozano, Sánchez-Martín, Porras and Guerrero.)

Background: Chronic lower limb ischemia develops earlier and more frequently in patients with type 2 diabetes mellitus. Diabetes remains the main cause of lower-extremity non-traumatic amputations. Current medical treatment, based on antiplatelet therapy and statins, has demonstrated deficient improvement of the disease. In recent years, research has shown that it is possible to improve tissue perfusion through therapeutic angiogenesis. Both in animal models and humans, it has been shown that cell therapy can induce therapeutic angiogenesis, making mesenchymal stromal cell-based therapy one of the most promising therapeutic alternatives. The aim of this study is to evaluate the feasibility, safety, and efficacy of cell therapy based on mesenchymal stromal cells derived from adipose tissue intramuscular administration to patients with type 2 diabetes mellitus with critical limb ischemia and without possibility of revascularization., Methods: A multicenter, randomized double-blind, placebo-controlled trial has been designed. Ninety eligible patients will be randomly assigned at a ratio 1:1:1 to one of the following: control group (n = 30), low-cell dose treatment group (n = 30), and high-cell dose treatment group (n = 30). Treatment will be administered in a single-dose way and patients will be followed for 12 months. Primary outcome (safety) will be evaluated by measuring the rate of adverse events within the study period. Secondary outcomes (efficacy) will be measured by assessing clinical, analytical, and imaging-test parameters. Tertiary outcome (quality of life) will be evaluated with SF-12 and VascuQol-6 scales., Discussion: Chronic lower limb ischemia has limited therapeutic options and constitutes a public health problem in both developed and underdeveloped countries. Given that the current treatment is not established in daily clinical practice, it is essential to provide evidence-based data that allow taking a step forward in its clinical development. Also, the multidisciplinary coordination exercise needed to develop this clinical trial protocol will undoubtfully be useful to conduct academic clinical trials in the field of cell therapy in the near future., Trial Registration: ClinicalTrials.gov NCT04466007 . Registered on January 07, 2020. All items from the World Health Organization Trial Registration Data Set are included within the body of the protocol., (© 2021. The Author(s).)

Background: Abdominal aortic aneurysm and acute appendicitis occur relatively frequently in elderly patients. However, the co-occurrence of the two pathologies is very rare and serious., Case Presentation: We present the case of an elderly Caucasian patient who was aware of having an abdominal aortic aneurysm but refused treatment and was subsequently admitted to the hospital's emergency department with acute abdominal symptoms. A computed tomography scan raised the possibility of complication due to the characteristics of the aneurysm. The patient then agreed to emergency surgery. Laparotomy revealed the existence of an acute perforated appendicitis with a significant abscess in the right iliac fossa and an uncomplicated aneurysm. Appendectomy was performed and the abscess drained. The postoperative period passed without complications, and the patient again refused surgery for the aneurysm, which due to its anatomical characteristics was not a candidate for standard endovascular treatment., Conclusions: In light of this experience, we review the literature about the relationship between abdominal aortic aneurysm and acute appendicitis.

Background: Carotid paragangliomas are rare tumors. They are usually unique, non-secreting, resectable, and benign. However, additional rare cases of complex tumors (bilateral, secretory, nonresectable, or malignant) complicate the management and final outcomes., Methods: Records of paragangliomas from our hospital are reviewed. Criteria defining complex paragangliomas have been previously defined. These are compared with those of the simple group., Results: Fifty patients, two groups: simple (n = 39) and complex (n = 11). The patients in the complex group were significantly younger (47.7 vs 63.8 years). Postoperative nerve complications (45.4% vs 6.3%) and mortality during follow-up (27.3% vs 0%) were significantly more common in the complex group. Vascular complications (0% vs 3.1%) and early mortality (0%) were similarly in both groups., Conclusions: Patients with complex carotid paragangliomas are heterogeneous. The former are younger, exhibit a high degree of diagnostic and therapeutic complexity, and have poorer morbidity and mortality. Surgical experience and interdisciplinary collaboration are essential., (© 2020 Wiley Periodicals LLC.)

Patients with peripheral artery disease (PAD) are at a high risk not only for the classical cardiovascular (CV) outcomes (major adverse cardiovascular events; MACE) but also for vascular limb events (major adverse limb events; MALE). Therefore, a comprehensive approach for these patients should include both goals. However, the traditional antithrombotic approach with only antiplatelet agents (single or dual antiplatelet therapy) does not sufficiently reduce the risk of recurrent thrombotic events. Importantly, the underlying cause of atherosclerosis in patients with PAD implies both platelet activation and the initiation and promotion of coagulation cascade, in which Factor Xa plays a key role. Therefore, to reduce residual vascular risk, it is necessary to address both targets. In the Cardiovascular Outcomes for People Using Anticoagulation Strategies (COMPASS) trial that included patients with stable atherosclerotic vascular disease, the rivaroxaban plus aspirin strategy ( versus aspirin) markedly reduced the risk of both CV and limb outcomes, and related complications, with a good safety profile. In fact, the net clinical benefit outcome composed of MACE; MALE, including major amputation, and fatal or critical organ bleeding was significantly reduced by 28% with the COMPASS strategy, (hazard ratio: 0.72; 95% confidence interval: 0.59-0.87). Therefore, the rivaroxaban plus aspirin approach provides comprehensive protection and should be considered for most patients with PAD at high risk of such events., Competing Interests: Disclosure and potential conflicts of interest: JLH reports consulting fees and/or lectures honoraria from Bayer, Daiichi Sankyo, Sanofi, Abbie, and AMGEN. FSL received compensation for advisory-board membership from Boehringer-Ingelheim, Bayer Health Care, Daiichi Sankyo, Rovi, and Sanofi-Aventis; and lectures fees from Bayer Health Care, Daiichi Sankyo, Glaxo Smith Kline, Leo Pharma, Menarini, Rovi, and Sanofi-Aventis. VR reports consulting fees from Bayer, Sanofi, and AstraZeneca. MAD reports consulting fees and/or lectures honoraria from AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb/Pfizer, Eli Lilly, GlaxoSmithKline, Daiichi-Sankyo, Rovi Pharmaceuticals, and Sanofi Aventis, and grants support from AstraZeneca. JCS reports consulting fees and/or lectures honoraria from AstraZeneca, Bayer, Boehringer Ingelheim, Daiichi Sankyo, and Pfizer-BMS. SBM reports consulting fees from Bayer. JGA reports consulting fees and/or lectures honoraria from Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, and Daiichi Sankyo. XGM reports consulting fees and/or lectures honoraria and/or advisory-board membership with Astra-Zeneca, Bayer, Boehringer-Ingelheim, Daiichi Sankyo, and Bristol-Myers Squibb/Pfizer. JJGD reports consulting fees and/or lectures honoraria from Bayer, Boehringer Ingelheim, AstraZeneca, and Daiichi Sankyo. JRGJ reports honoraria for lectures and advisory board from Bayer. CSF reports consulting fees and/or lectures honoraria from Bayer, Daiichi Sankyo, Pfizer-BMS and SBM. The International Committee of Medical Journal Editors (ICMJE) Potential Conflicts of Interests form for the authors is available for download at: https://www.drugsincontext.com/wp-content/uploads/2020/06/dic.2020-5-5-COI.pdf, (Copyright © 2020 Hernández JL, Lozano FS, Riambau V, Almendro-Delia M, Cosín-Sales J, Bellmunt-Montoya S, Garcia-Alegria J, Garcia-Moll X, Gomez-Doblas JJ, Gonzalez-Juanatey JR, Suarez Fernández C.)

Introduction: In this review, the role of the rivaroxaban-plus-aspirin approach (dual pathway inhibition - DPI) in patients with chronic coronary syndrome (CCS) and to perform practical recommendations about its use was updated., Areas Covered: The contents of this review were proposed in an expert meeting. To identify relevant articles, a systematic search of Medline/Embase was performed (to July 2019), using the key words 'rivaroxaban', 'vascular dose', 'COMPASS' and 'coronary artery disease' in the search strategy., Expert Opinion: Despite current antithrombotic strategies (single/dual antiplatelet therapy) have decreased rates of recurrent cardiovascular events among patients with CCS, residual risk remains unacceptably high. The COMPASS trial showed in CCS patients that compared with aspirin 100 mg rivaroxaban 2.5 mg bid plus aspirin 100 mg reduced the risk of major cardiac events, cardiovascular hospitalization and mortality, without an increase of intracranial or fatal bleedings. Importantly, residual risk with the rivaroxaban plus aspirin approach was lower than with different dual antiplatelet therapy regimens. The rivaroxaban plus aspirin strategy is of particular benefit in patients with CCS and high-risk cardiovascular feature (i.e. ≥2 vascular beds, heart failure, renal insufficiency, peripheral artery disease, previous stroke or diabetes) and should be considered in these populations.

We report on the case of spontaneous rupture of an On-X-pure pyrolytic carbon mechanical valve prosthesis implanted seven years earlier, in a mitral position, at our hospital. The patient was admitted with valvular dysfunction and acute pulmonary edema requiring emergency surgery (prosthesis replacement); the absence of a leaflet was confirmed intraoperatively. The patient presented severe respiratory failure, which prolonged the postoperative period. A CT scan showed that the migrated leaflet was located in the aortic bifurcation with no apparent arterial lesion. Four months later, once the patient had recovered, laparotomy and aortotomy were performed in order to retrieve the leaflet, which was found to have become included (neoendothelized) in the aortic wall without compromising the latter's integrity or obstructing the blood flow. A subsequent CT scan confirmed the persistence of the leaflet in its initial position. The literature review highlights two singular facts: 1) this is the second published case of the escape of a leaflet from an On-X prosthesis (the first patient died); 2) this is the first case in which a laparotomy was performed to retrieve the leaflet but finally a decision was made to leave it in situ. Seven months later, the patient remained asymptomatic.

Cell therapy is a progressively growing field that is rapidly moving from preclinical model development to clinical application. Outcomes obtained from clinical trials reveal the therapeutic potential of stem cell-based therapy to deal with unmet medical treatment needs for several disorders with no therapeutic options. Among adult stem cells, mesenchymal stem cells (MSCs) are the leading cell type used in advanced therapies for the treatment of autoimmune, inflammatory and vascular diseases. To date, the safety and feasibility of autologous MSC-based therapy has been established; however, their indiscriminate use has resulted in mixed outcomes in preclinical and clinical studies. While MSCs derived from diverse tissues share common properties depending on the type of clinical application, they markedly differ within clinical trials in terms of efficacy, resulting in many unanswered questions regarding the application of MSCs. Additionally, our experience in clinical trials related to critical limb ischemia pathology (CLI) shows that the therapeutic efficacy of these cells in different animal models has only been partially reproduced in humans through clinical trials. Therefore, it is crucial to develop new research to identify pitfalls, to optimize procedures and to clarify the repair mechanisms used by these cells, as well as to be able to offer a next generation of stem cell that can be routinely used in a cost-effective and safe manner in stem cell-based therapies targeting CLI.

Thromboangiitis obliterans (TAO), also known as Buerger's Disease, is an occlusive vasculitis linked with high morbidity and amputation risk. To date, TAO is deemed incurable due to the lack of a definitive treatment. The immune system and inflammation are proposed to play a central role in TAO pathogenesis. Due to their immunomodulatory effects, mesenchymal stromal cells (MSCs) are the subject of intense research for the treatment of a wide range of immune-mediated diseases. Thus far, local intramuscular injections of autologous or allogeneic MSCs have shown promising results in TAO. However, sequential intravenous allogeneic MSC administration has not yet been explored, which we hypothesized could exert a systemic anti-inflammatory effect in the vasculature and modulate the immune response. Here, we report the first case of a TAO patient at amputation risk treated with four sequential intravenous infusions of bone marrow-derived allogeneic MSCs from a healthy donor. Following administration, there was significant regression of foot skin ulcers and improvements in rest pain, Walking Impairment Questionnaire scores, and quality of life. Sixteen months after the infusion, the patient had not required any further amputations. This report highlights the potential of sequential allogeneic MSC infusions as an effective treatment for TAO, warranting further studies to compare this approach with the more conventionally used intramuscular MSC administration and other cell-based therapies.

Background: Pain control in critical limb ischemia (CLI) varies considerably between individuals., Objective: To evaluate pharmacogenetically the response to transdermal buprenorphine (BUP-TTS) in patients with CLI who are awaiting revascularization., Methods: One hundred and seven patients with CLI were treated with BUP-TTS. The following were analyzed: (1) pain perception (visual analog scale (VAS) before and 4 days after treatment) and (2) genetics: glucuronosyltransferase (UGT2B7), cytochrome (CYP3A4), and μ-opioid receptor (OPRM1) gene polymorphisms., Results: Ninety-three patients completed the study. The VAS score by the fourth day of analgesia dropped from 6.82 to 3.38 (P < 0.05). The analgesic response to BUP-TTS was greater in men than in women (P = 0.019). Patients who were AA homozygotes for the CYP3A4 gene showed the best response to analgesic treatment (P = 0.003). The combination of the CYP3A4 gene with UGT2B7 or OPRM1 was favorable to the effect of the CYP3A4 gene (P = 0.045 and P = 0.026, respectively). The combination of UGT2B7 with OPRM1 was ineffective (P = 0.648). The 3 polymorphisms together had no effect on response to treatment (P = 0.461)., Conclusions: BUP-TTS is efficacious in the control of pain in patients with CLI. The homozygous AA carriers of the CYP3A4 gene respond better to treatment with BUP-TTS., (© 2015 World Institute of Pain.)

Background: Experience is limited with regard to antithrombotic therapy in patients with venous thromboembolism (VTE) following allogeneic hematopoietic stem cell transplantation (HSCT)., Design and Methods: We described a cohort of patients presenting with symptomatic VTE following allogeneic HSCT, including management patterns and outcomes., Results: Twenty-four patients developed a deep vein thrombosis and/or pulmonary embolism unrelated to a catheter. Median time of VTE diagnosis and duration of antithrombotic therapy were 9.5 and 6months. Eleven patients were treated with full-dose low molecular weight heparin (LMWH). Eleven patients with minor bleeding, thrombocytopenia or renal failure received prophylactic dose LMWH. In two patients an inferior vena cava filter was inserted due to thrombocytopenia and bleeding. There were 2 major and 4 life-threatening bleeding episodes, so LMWH was discontinued permanently. Two deaths were directly attributable to bleeding. Ten patients developed a catheter-associated VTE. Median time to diagnosis and duration of anticoagulation was 2.5 and 3months. Catheter was removed in all patients. LMWH was administered at therapeutic-dose in 4 patients, and was reduced by bleeding in 2 of them. LMWH was administered at prophylactic-dose in 6 patients, and was reduced by renal failure in one patient. There were three episodes of minor bleeding. Rate of clot recurrence was 29.4% (n=10). Patients at recurrence were without antithrombotic treatment (n=4), intermediate-dose LMWH (n=2), low-dose LMWH (n=2) or acenocumarol (n=2). Eight patients with recurrence VTE had extensive chronic graft versus host disease (GVHD)., Conclusions: LMWH was used in most HSCT recipients but half of them may not receive full-dose LMWH. Thrombocytopenia, renal impairment and bleeding were the reasons for reducing LMWH. Also, rates of clinically relevant hemorrhage or recurrent VTE were highly significant. The development of GVHD could mainly explain these findings., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background: Prosthetic material (mesh) is commonly used to repair inguinal hernias. Its implantation close to the common femoral vein (CFV) can induce slow flow and favor the appearance of venous thromboembolism (VTE) events., Aim: To investigate the speed of flow, diameter and area of the CFV after inguinal hernioplasty., Methods: Two hundred and fifty patients receiving open hernioplasty with a non-resorbable mesh for the repair of a unilateral, primary, simple inguinal hernia were prospectively investigated. Patients were stratified, by consensus, into a low or a moderate risk of VTE group. The moderate-risk group (n = 163) received low molecular weight heparin. On day 10 post-operation a blinded Echo-Doppler was carried out, and repeated 7 days later in patients with a venous flow of <15 cm/s. The speed of flow (cm/s), diameter (cm), and area (cm(2)) of the ipsilateral and contralateral CFV of the groin operated upon were measured., Results: No event symptomatic of VTE was documented. One case of asymptomatic deep vein thrombosis (1/163, 0.6%) was found in the moderate-risk group. In 29 patients (2 and 27 in the low- and moderate-risk groups, respectively; p < 0.001) a maximum blood flow velocity of <15 cm/s was found in the ipsilateral CFV; these flows were close to normal in the second measurement. Taking the entire sample into account, the maximum venous blood flow found in the ipsilateral CFV of the operated groin was less than that measured in the contralateral CFV (20.88 vs. 24.01 cm/s; p < 0.001); this difference was significant in both VTE risk groups. The diameter and area of the CFV were both greater in the ipsilateral than the contralateral CFV (p < 0.01); this finding proved to be significant only in hernias of the left groin (p < 0.001)., Conclusions: In the immediate postoperative period, inguinal hernioplasty with mesh induces a temporarily slow venous flow in the ipsilateral CFV. However, this does not lead to an increase in the incidence of VTE.

Bleeding is a frequent complication after allogeneic haematopoietic stem cell transplantation (HSCT) and may affect survival. The purpose of this study was to determine the incidence and risk factors for life-threatening bleeding after HSCT by retrospective evaluation of 491 allogeneic HSCT recipients. With a median follow-up of 33 months, 126 out of 491 allogeneic HSCT recipients experienced a haemorrhagic event (25·7%) and 46 patients developed a life-threatening bleeding episode (9·4%). Pulmonary and gastrointestinal bleeding were the most common sites for life-threatening bleeding, followed by central nervous system. In multivariate analyses, the presence of severe thrombocytopenia after day +28 and the development of grade III-IV acute graft-versus-host disease (GVHD) or thrombotic microangiopathy (TMA) retained their association with life-threatening bleeding events. The overall survival at 3 years among patients without bleeding was 67·1% for only 17·1% for patients with life-threatening bleeding (P < 0·001). In conclusion, life-threatening bleeding is a common complication after allogeneic HSCT. Prolonged severe thrombocytopenia, acute grade III-IV GVHD and TMA were associated with its development., (© 2015 John Wiley & Sons Ltd.)

Anticoagulation therapy is the standard treatment of patients with symptomatic venous thromboembolism (VTE), including deep vein thrombosis and pulmonary embolism. Until recently, treatment of VTE was based on parenteral or low-molecular-weight heparin for initial therapy (5-10 days) and oral vitamin K antagonists for long-term therapy. Those treatments have some limitations, including parenteral administration (heparins), the need for frequent monitoring and dose adjustments, interactions with several medications, and dietary restrictions (vitamin K antagonists). Rivaroxaban is a new oral direct factor Xa inhibitor with a wide therapeutic window, predictable anticoagulant effect, no food interactions, and few drug interactions. Consequently, no periodic monitoring of anticoagulation is needed, and fixed doses can be prescribed. EINSTEIN program demonstrated that rivaroxaban was as effective as and significantly safer than standard therapy for treatment of VTE. Rivaroxaban was recently authorized so doubts exist about how to use it in daily clinical practice. This document aims to clarify common questions formulated by clinicians regarding the use of this new drug., (© The Author(s) 2014.)

Introduction: The Ankle-Brachial Index (ABI) makes it possible to identify patients with peripheral artery disease (PAD). Intermittent claudication (IC) is the first major symptom of PAD, although many patients with an ABI ≤ 0.9 do not exhibit IC, and the range of ABI among those who do have IC is very variable. This study evaluates the correlation between ABI and the perception (symptomatology) of claudicant patients., Material and Methods: An observational, cross-sectional and multicentre, study of 920 patients with IC. Clinical history, ABI, Walking Impairment Questionnaire (WIQ) and European Quality of Life Questionnaire (EQ-5D) were recorded. Associations were analysed using Spearman's correlation coefficient., Results: The mean ABI of the series was 0.63 (SD = 0.19). The mean WIQ-distance was 34.07 (SD = 26.77), values being smaller for lower ABI values (r = 0.343, p < 0.001). The mean EQ-5D score of the series was 0.58 (SD = 0.21), also showing lower values as the ABI decreased (r = 0.278, p < 0.001). The correlations of WIQ and EQ-5D with ABI were statistically significant in both cases, but always less than 0.400 (between 0.278 and 0.343)., Conclusions: The correlations of ABI with the questionnaires of walking capacity and quality of life are weak. For this reason, although in clinical practice the ABI of CI patients is commonly measured, decisions should not be taken during the development of IC exclusively on the basis of the ABI., (© 2014 John Wiley & Sons Ltd.)

Background: Intermittent claudication (IC) and its consequences have customarily been underestimated in women. Our study aimed to determine the differences on functional and quality-of-life issues between women and men in a large group of claudicants., Methods: This study was an observational, cross-sectional, nonrandomized, multicenter study of 1,641 claudicants (406 women). Information was collected from patients' medical history, a physical examination, the ankle-brachial index (ABI), the Walking Impairment Questionnaire (WIQ), and the European Quality of Life Questionnaire (EQ-5D)., Results: On average, women with IC were older than men with IC (70.0 vs. 67.8 years; p<0.001) and tended to have a different socio-occupational status. Women were more likely to be obese and less likely to smoke or have dyslipidemia (p<0.001). Women were notable for their greater prevalence of cardiac insufficiency (p=0.016) and arrhythmias (p<0.001) and a lower prevalence of ischemic cardiopathy and acute myocardial infarction (p<0.001). At the same time, there was a significantly higher level of osteoarticular diseases in women: arthrosis (p<0.001), arthritis (p<0.001), and lumbar pathology (p=0.006). All the symptoms evaluated that were associated with IC were more frequent in women (p<0.05). The mean ABI was similar in claudicant women and men. Conversely, the parameter estimates of the WIQ were significantly lower in women (by 4.3%, and 6.5%, respectively; p=0.003). Likewise, the EQ-5D score was 7% lower in women than in men (from 0.52 to 0.59; p<0.001)., Conclusions: Women claudicants have higher risk factors and more frequent cardiovascular comorbidity than men do. Women have a lower capacity for exercise and a poorer quality of life than male claudicants, despite having a similar ABI. These poorer outcomes in women can be partially explained by the presence of greater osteoarticular comorbidity.

Introduction: Diabetes mellitus (DM) and intermittent claudication (IC) are frequently associated health conditions. Our hypothesis is that the nature, severity and quality of life (QoL) of patients with IC and DM are worse than those of claudicant patients without diabetes., Material and Methods: An observational, cross-sectional and multicentre study of 920 patients with IC, divided into two groups: diabetic (n = 477) and non-diabetic (n = 443). For each group, we examined clinical and biological characteristics (including levels of glucose and lipids), the ankle-brachial index (ABI), responses to the Walking Impairment Questionnaire (WIQ) and the European Quality of Life-5 Dimensions (EQ-5D) questionnaire., Results: Compared with claudicant patients without diabetes, claudicants with diabetes were older (p < 0.001), more likely to be female (p = 0.006), with a higher BMI (p < 0.001), more likely to have a sedentary lifestyle (p < 0.001) and to be a non-smoker (p < 0.001). Claudicant patients with diabetes also had significantly more cardiovascular risk factors (p < 0.001), more frequent ischaemic cardiopathy (p = 0.023) and chronic renal failure (p = 0.002), and fewer prior ictus events (p = 0.003). No significant differences between groups were found with respect to blood pressure, levels of cholesterol or triglycerides. The mean ABI of diabetic-IC patients was slightly lower than IC patients without diabetes (p = 0.016). All WIQ subdomains scores were significantly lower (p < 0.001), indicating poorer walking ability, in claudicant and diabetic patients with compared with those without diabetes. The mean E5-QD global scores and the mean EQ-5D visual analogue scale in the whole series were 0.58 (SD = 0.21) and 55.04 (SD = 21.30), respectively. Both E5-QD scores were significantly lower, indicating poorer QoL, in claudicant patients with diabetes than claudicant patients without diabetes (p < 0.001)., Conclusion: Patients with IC and DM had more risk cardiovascular factors, cardiovascular conditions, disability and worse haemodynamic status and QoL than claudicant patients without diabetes.

Background: The goal of this article is to present for the first time to the international community the detailed findings and outcomes of the Spanish Vascular Registry (SVR) after 16 years of experience., Methods: We examined the nationwide registry promoted by the Spanish Society of Angiology and Vascular Surgery (1996-2011). The changes in vascular surgical activity in Spain during the period of study were examined. We evaluated the number of services, medical specialists, consultations, admissions, and operations that occurred in Spain. We also assessed the trends in therapeutic activity and the medical and social impact of vascular pathology., Results: A mean of 60 centers (range = 32-83) participated in the SVR (79.3 % of the total). In the last year of the study period, 94.3 % centers (100 % of teaching centers) participated. The mean number of activities per hospital per year was 5,298 consultations, 2,625 vascular explorations, 630 hospital admissions (61 % elective and 31 % emergency), and 742 surgical procedures. A total of 29,289 carotid stenosis procedures had been registered over 16 years. Both carotid endarterectomy (CEA) and carotid artery stenting (CAS) procedures have increased in frequency over time. In 2011, CAS constituted 19.3 % of all carotid procedures. A total of 31,703 abdominal aortic aneurysm (AAA) operations were registered during the study period. Surgery for ruptured AAA remained stable over time. Since its appearance in the year 2000, endovascular treatment (EVAR) increased steadily over time. Currently, EVAR represents about half of all AAA surgery (50.2 %). The total rate of in-hospital operative deaths was 1.1 %, but in-hospital mortality for open arterial surgery was 4 %. Mortality has decreased of late., Conclusions: The SVR has enabled us to understand the development and implementation of vascular surgery throughout Spain and to note the increased healthcare activity and the better overall results obtained as a consequence.

Background: The Walking Impairment Questionnaire (WIQ) is a short, easy to complete, disease-specific questionnaire to assess intermittent claudication. A Spanish version of the WIQ for Hispanic Americans has recently been validated in Texas, but it needs to be validated for European Spanish people., Patients and Methods: After translation and cultural adaptation of the WIQ, 920 patients with intermittent claudication (ankle brachial index < 0.9) completed two questionnaires (Spanish version of the WIQ and European Quality of Life 5 Dimension [EQ-5D]). The validity of the WIQ was determined by correlating WIQ and EQ-5D. Test-retest reliability and internal consistency were determined using the intra-class correlation coefficient (ICC) and Cronbach's alpha, respectively., Results: The three domains of the WIQ were moderately correlated with the EQ-5D health outcome (r = 0.54 to 0.60; p < 0.001). Test-retest reliabilities ranged from ICC = 0.89 to 0.91 and internal consistency (Cronbach's alpha = 0.92) was high., Conclusions: The Spanish version of the WIQ for European Spanish patients was valid and reproducible, suggesting that it could be used in Spanish patients with intermittent claudication.

Allogeneic hematopoietic stem cell transplantation recipients have an increasing risk of both hemorrhagic and thrombotic complications. However, the competing risks of two of these life-threatening complications in these complex patients have still not been well defined. We retrospectively analyzed data from 431 allogeneic transplantation recipients to identify the incidence, risk factors and mortality due to thrombosis and bleeding. Significant clinical bleeding was more frequent than symptomatic thrombosis. The cumulative incidence of a bleeding episode was 30.2% at 14 years. The cumulative incidence of a venous or arterial thrombosis at 14 years was 11.8% and 4.1%, respectively. The analysis of competing factors for venous thrombosis revealed extensive chronic graft-versus-host disease to be the only independent prognostic risk factor. By contrast, six factors were associated with an increased risk of bleeding; advanced disease, ablative conditioning regimen, umbilical cord blood transplantation, anticoagulation, acute III-IV graft-versus-host disease, and transplant-associated microangiopathy. The development of thrombosis did not significantly affect overall survival (P=0.856). However, significant clinical bleeding was associated with inferior survival (P<0.001). In allogeneic hematopoietic stem cell transplantation, significant clinical bleeding is more common than thrombotic complications and affects survival.

Background: Few studies have evaluated the risk of pregnancy-related adverse events in asymptomatic relatives of probands for VTE and factor V Leiden or the G20210A variant. The antepartum management of this population ranges from antepartum anticoagulation therapy to clinical surveillance., Objective: To evaluate the risk of placenta-mediated pregnancy complications and pregnancy-related VTE in VTE-asymptomatic families of probands with VTE and who are heterozygous carriers of either factor V Leiden or PT-G20210A mutation., Methods: One hundred and fifty-eight relatives, who had 415 pregnancies, were retrospectively evaluated. Odds ratios and 95% confidence intervals were calculated to compare pregnancy outcomes between women with and without thrombophilia., Results: In the factor V Leiden group, 22 placenta-mediated pregnancy events of 152 pregnancies (14.4%) were reported, compared with 25 adverse events of 172 pregnancies in the G20210A prothrombin group (14.5%) and 13 adverse events of 91 pregnancies in the non-carrier group (14.2%). Carriers of factor V Leiden or G20210A prothrombin were not associated with a higher risk of pregnancy-adverse outcomes compared with non-carriers: OR 1.02 (95% CI, 0.40-2.25) and 1.25 (95% CI, 0.48-3.24), respectively. Four episodes of pregnancy-associated VTE of 415 pregnancies (0.96%) were recorded. Two episodes of VTE in the G20210A group, one in the factor V Leiden group, and one episode in the non-carrier group were noted., Conclusions: In VTE-asymptomatic relatives of probands with VTE, the presence of factor V Leiden or the G20210A prothrombin mutation in heterozygosis should not lead to a decision to instigate antepartum prophylaxis., (© 2012 John Wiley & Sons A/S.)

Background: The factorial instability of the CIVIQ-20 social dimension in different populations has necessitated the development of a new stable questionnaire to interpret results from international studies., Objective: Construction of a stable and psychometrically validated questionnaire from CIVIQ-20., Methods and Major Findings: A prospective, international study was used to construct a stable CIVIQ scale and to validate its psychometric properties. An iterative process was implemented to eliminate the more unstable items (six), and the social and physical dimensions were combined. The resulting instrument comprised 14 items, split into three dimensions (pain, physical, and psychological), and was named CIVIQ-14. The stability of the CIVIQ-14 factorial structure was confirmed in Polish, Czech, Spanish, and French populations using principal component analysis and multitrait/multimethod analysis. Psychometric assessment demonstrated that CIVIQ-14 was reliable (intra-class coefficient >0.8; weighted kappa >0.8), valid (correlation coefficients between dimension scores and clinical severity scores between 0.3 and 0.6), and sensitive (effect sizes >0.6 for psychological dimension; >0.8 for the other dimensions)., Conclusion: CIVIQ-14 is a reliable, valid, and sensitive instrument applicable to international studies of patients with chronic venous disease.

Background: Pseudoaneurysms of the superior mesenteric artery are rare, and their natural history is characterized by their tendency to rupture, thereby leading to a high mortality rate. Compared with classic surgical techniques (open), in recent years the possibility of endovascular treatment has increased., Results: We report the cases of two patients with a pseudoaneurysm of the superior mesenteric artery. Each case was successfully treated in a different way: open and endovascular surgery., Conclusion: Despite the advantages (less risk for the patient) and good results obtained with endovascular surgery, this cannot completely replace open surgery. The choice of the most appropriate therapeutic option for pseudoaneurysms of the superior mesenteric artery depends on the state of the patient and the characteristics of the lesion. Open and endovascular surgical techniques are complementary, not mutually exclusive, techniques., (Copyright (c) 2010. Published by Elsevier Inc.)

Since the beginning of the 1990s, the prevalence of isolates of non-typhoidal Salmonella species resistant to antimicrobial agents, including those commonly used for the treatment of Salmonella infections such as fluoroquinolones, trimethoprim-sulfamethoxazole or beta-lactams, has increased substantially. Infections caused by multidrug-resistant strains of non-typhoidal Salmonella are now frequently encountered. In order to consider an appropriate role of Ertapenem in Salmonella-due intraabdominal infections, in the present study we compare the efficacy of Ertapenem versus that of Ceftriaxone in a mouse peritonitis model. Bacteriological eradication from blood, liver and mesenteric lymph nodes was observed after 5 and 7 days of treatment in all infected mice receiving ceftriaxone. Although both antimicrobial agents -Ertapenem and Ceftriaxone- were observed to be effective in reducing mortality in inoculated mice, our data suggests a reduced efficacy of Ertapenem in the bacteriological eradication of Salmonella enterica serotype Typhimurium in a mouse peritonitis model.

Despite preventive efforts, venous thromboembolic disease (VTED) is still a major problem for surgeons due to its frequency and the morbidity, mortality and enormous resource consumption caused by this entity. However, the most important feature of VTED is that it is one of the most easily preventable complications and causes of death. To take appropriate prophylactic decisions (indication, method, initiation, duration, etc.), familiarity with the epidemiology of VTED in general surgery and some of its most significant populations (oncologic, laparoscopic, bariatric, ambulatory and short-stay) is essential. These factors must also be known to determine the distinct risk factors in these settings with a view to stratifying preoperative risk.

Postoperative venous thromboembolic disease (VTED) affects approximately one in four general surgery patients who do not receive preventive measures. In addition to the risk of pulmonary embolism, which is often fatal, patients with VTED may develop long-term complications such as post-thrombotic syndrome or chronic pulmonary hypertension. In addition, postoperative VTED is usually asymptomatic or produces clinical manifestations that are attributed to other processes and consequently this complication is often unnoticed by the surgeon who performed the procedure. Thus, the most effective strategy consists of effective prevention of VTED using the most appropriate prophylactic measures against the patient's thromboembolic risk. There is sufficient evidence that VTED can be prevented by pharmacological methods, especially heparin and its derivatives and with mechanical methods such as support tights or intermittent pneumatic compression of the lower extremities. To reduce the incidence of VTED as far as possible, strategies have been proposed that include a combination of drugs and mechanical methods, new antithrombotic drugs, or prolonging the duration of prophylaxis in patients at very high risk, such as those who have undergone surgery for cancer. Another important aspect is the optimal moment to initiate prophylaxis with anticoagulant drugs with the aim of achieving an adequate equilibrium between antithrombotic efficacy and the risk of hemorrhagic complications. The present article reviews the available evidence to attempt to optimize prevention of VTED in general surgery and in some special groups, such as laparoscopic surgery, short-stay surgery and obesity.

Aim: The aim of this study was to investigate the prevalence and initial treatment of chronic venous disease (CVD) in the Spanish primary health care system during 2006 and to compare the results with those obtained in 2000., Methods: The survey involved 1 118 general practitioners co-ordinated by 37 specialists in angiology and vascular surgery, assessing 15 consecutive patients, each attending the clinics between 29 May and 2 June 2006., Results: Of the16 186 patients reported, 82% had CVD risk factors. When asked about CVD signs or symptoms 11 277 patients (69.7%) mentioned some kind of clinical manifestation/sign compatible with the disease. Diagnosis was established in accordance with the clinical section of the CEAP classification, 38% of the total being classified as C2-C6. Sixty-two percent of the symptomatic patients had received prior treatment (vs 24.8% in year 2000), and following the survey 88% of the patients diagnosed with CVD were treated (vs 62% in 2000)., Conclusions: The results for 2006 confirm the high prevalence of CVD in primary health care in Spain. In comparison with the results for 2000, an improvement in the patterns of medical advice use, treatment and prescriptions are observed. Despite these findings, specific training programs in primary health care regarding the diagnosis and treatment of CVD continue to be necessary.

Background and Aims: Vagal paragangliomas (VPs) represent a rare pathology in which surgery is usually recommended, but where experience is crucial to reduce the number of post-operative complications. In this study, we present our experience and a review of the literature., Methods: Between 1991 and 2006 we have treated 42 patients with 50 paragangliomas of the head and neck (26 carotid, 18 jugular/tympanic and 6 vagal). Examination of the literature (Medline and non-indexed Spanish source) from the last 30 years has revealed 23 series that each reported more than three cases; reaching a total of 332 VPs., Results: VPs are infrequent among paragangliomas of the head and neck (6/50) presenting clinical peculiarities such as multiple tumours, and malignant evolution. Within this current series, surgery was possible in all cases. Post-operative dysfunction in cranial nerves was frequent (the cranial X nerve was systematically sacrificed). There were no bronco-aspirations or mortalities. The literature review reveals similar results., Conclusion: To obtain the best results, it is important that the candidates for surgery be selected by experts within multidisciplinary groups.

When neck cancer affects the carotid artery, the best therapeutic option is to remove the tumor en bloc, including the affected vessels. When the carotid artery is revascularized, the usual practice according to the literature is to replace the defective carotid artery with an autologous graft from the saphenous vein, although it is also possible to use an autologous superficial femoral artery (SFA). The use of the SFA in oncologic surgery does not seem to be widespread; in fact, we only found 7 references (67 cases). Here we report three cases in which the SFA was employed and offer a review of the literature. The SFA has advantages and disadvantages in comparison with the saphenous vein. The need for interdisciplinary collaboration (otorhinolaryngology/vascular surgery) is very important, especially in situations where the saphenous vein is not available.

The aim of this study was to design an aggressive nonlethal animal model that would simulate surgical treatment of the abdominal aorta with a view to studying the systemic inflammatory response. Fourteen pigs were subjected to two sequential experiments. Experiment A was performed to determine the response to two degrees of hemorrhage: (A1) 40% bleeding; and (A2) 60% bleeding over 15 minutes followed by midline laparotomy and aortic dissection. Experiment B included two methods of aortic repair: (B1) aortic resection and replacement with a prosthesis; and (B2) aortic bypass without aortic resection. In the latter two groups, suprarenal aortic cross-clamping was placed for 30 minutes after a 40% hemorrhage. We analyzed various inflammatory markers and mortality. The 40% bleeding (vs. 60%) elicited a smaller decrease in mean arterial pressure (110 +/- 6 vs. 89 +/- 9 mmHg) but did not cause irreversible shock or mortality. After the 40% hemorrhage, the B1 aortic repair caused two cases of paraplegia. We have developed a model to study the combined effect of bleeding and aortic cross-clamping.

Background: Propofol has been reported to provide protection against ischemia-reperfusion injury. Nuclear transcription factor kappa B (NFkappaB) plays a key role in oxidative stress and the inflammatory response during ischemia-reperfusion. We compared the effect of propofol with sevoflurane on kidney NFkappaB expression and systemic inflammatory responses induced by aortic clamping., Methods: Twenty piglets were divided into four groups: sham surgery group with propofol (group SP, n = 5); sham group with sevoflurane (group SS, n = 5); and suprarenal clamping for 30 min with aorta-aortic bypass under propofol (group CP, n = 5) or sevoflurane (group CS, n = 5) anesthesia. Propofol was administered at 4 mg x kg(-1) x h(-1) i.v. and sevoflurane given at 1.5% inspiratory concentration. Peripheral blood and kidney biopsies were taken before the start of surgery, 15 min after unclamping the aorta, 24, 48, 72 h, and 7 days after surgery. Plasma creatinine, myeloperoxidase, tumor necrosis factor-alpha, interleukin 1-beta; and kidney superoxide anion and superoxidase dismutase were measured. The expression of inducible nitric oxide synthase and renal tissue NFkappaB was measured using Western blotting., Results: Compared with the CS group, animals in the CP group had lower concentrations of myeloperoxidase, tumor necrosis factor-alpha, interleukin 1beta, superoxide anion, superoxidase dismutase (P < 0.05) from 24 to 72 h after surgery and diminished NFkappaB expression and inducible nitric oxide synthase activity (P < 0.05) at 48 and 72 h after surgery, respectively., Conclusions: Compared with sevoflurane, propofol administration during suprarenal aortic clamping and unclamping led to modulation of markers of inflammation and decreased NFkappaB expression.

Background: Several experimental studies have shown the beneficial effects of nitric oxide (NO) in the modulation of the systemic inflammatory response syndrome (SIRS). Nitric oxide is involved in and affects almost all stages in the development of inflammation. We have attempted to ascertain whether the nitric oxide donor molsidomine prevents aortic graft contamination through control of the SIRS and a decrease in bacterial translocation (BT)., Methods: Twenty-four mini-pigs were divided into 4 groups. The animals were subjected to suprarenal aortic/iliac cross-clamping (for 30 minutes) and by-pass with a Dacron-collagen prosthetic graft impregnated in rifampicin. Groups: 1) sham (aortic dissection alone); 2) cross-clamping and bypass; 3) hemorrhage of 40% of total blood volume before cross-clamping and by-pass; and 4) the same as in group 3 but also including the administration of the NO donor molsidomine (4 mg/kg) 5 minutes before cross-clamping., Variables: 1) bacteriology of mesenteric lymph nodes (MLN), kidney, blood, and prosthesis; 2) serum TNF-alpha (ELISA); and 3) iNOS expression in kidney and liver (Western blot)., Results: Aortic cross-clamping with or without hemorrhage was associated with BT in 80% and 100% of the animals, respectively. About 86% of the bacteria isolated in the graft were also present in MLN. This contamination coincided with an increase in TNF-alpha and with a greater expression of iNOS. Molsidomine administration decreased TNF-alpha and iNOS, decreased BT (from 100% to 20% of the animals), and decreased graft contamination (from 83% to 20%)., Conclusions: The present model induces high levels of BT and SIRS, both acted as sources of contamination for the implanted Dacron graft. Molsidomine administration decreased the presence of bacteria in the graft by controlling BT and modulating SIRS.

Purpose: A laboratory investigation was undertaken to assess the effects of propofol on renal function, through modulation of the systemic inflammatory response, in an in vivo experimental model of aortic surgery in comparison with sevoflurane., Methods: Twenty young male piglets were anesthetized with either propofol 4 mg.kg(-1).hr(-1) (n = 10) or sevoflurane 1.5% end-tidal concentration (n = 10). Animals were subjected to aorta-aortic bypass with suprarenal aortic clamping for 30 min. At specific intervals (basal -before the start of surgery; reperfusion 15 min after unclamping the aorta; at 24, 48 and 72 hr after surgery, and on the seventh day after surgery) the levels of the following were determined: plasma creatinine, renal myeloperoxidase, tumour necrosis factor-alpha, interleukin 1-ss, and interferon-gamma; kidney superoxide anion and its detoxifying enzyme superoxidase dismutase, kidney malondialdehyde and the activity of inducible nitric oxide synthase. Seven days after surgery, the animals were anesthetized using the described techniques, and after blood withdrawal and kidney sampling they were sacrificed., Results: In comparison with sevoflurane, propofol was associated with a lower concentration of plasma creatinine (P < 0.05) together with lower concentrations of myeloperoxidase, tumour necrosis factor-alpha, interleukin 1-ss, interferon-gamma, superoxide anion and superoxidase dismutase, malondialdehyde and inducible nitric oxide synthase (P < 0.05)., Conclusion: In an experimental model of aortic reconstructive surgery, and compared with sevoflurane, propofol anesthesia is associated with less neutrophil infiltration, lower plasma proinflammatory cytokine levels, lower production of oxygen free radicals, less lipid peroxidation, and reduced inducible nitric oxide synthase activity. These observations suggest a possible renal protective effect of propofol in this surgical setting.

The authors report the unusual case of a 52-year-old mountain climber that presented with pain and swelling in his right thigh which revealed to be a ruptured mycotic pseudoaneurysm with no history of recent trauma or other apparent cause. The patient reported a past history of myocardial infarction 11 years before, with the performing of two femoral catheterisms for coronary angiography. He denied any episode of fever or diagnosis of bacteraemia at that time or later, nor any other complaint during these 11 years. The rarity of the case, the appearance of this extremely late complication together with the patient's kind of sportive activity prompted us to publish the case.

Surgery of the abdominal aorta generates a systemic inflammatory response (SIR), a source of operative morbidity-mortality. In the present work we attempted to evaluate the evolution of SIR in an experimental model that simulates elective and urgent surgery on the abdominal aorta. Fifteen mini-pigs divided into three groups were used. The animals were subjected to suprarenal aortic/iliac clamping and bypass with a Dacron-collagen prosthetic graft. Groups were as follows: (1) sham (only aortic dissection); (2) clamping and bypass; (3) hemorrhage of 40%, pre-clamping, and bypass. Determinations included (1) tumor necrosis factor-alpha (TNF-alpha) interleukin (IL)-1beta, IL-6, IL-10, interferon-gamma; (2) myeloperoxidase (MPO), superoxide anion (SOA), superoxide dismutase (SOD), and malondialdehyde (MDA); (3) nitrites; (4) iNOS, (5) cell adhesion molecules (ICAM-1, VCAM-1) at 24 hours, 48 hours, and on day 7; and (6) NFkappaB at 48 hours. Our results point to an increase in all inflammatory variables, corroborated by their molecular regulators such as the expression of CAMs, iNOS, and NFkappaB. The alterations tended to normalize by day 7, after reperfusion. The results point to the great importance of SIR at all levels (molecular, nuclear, cellular, and systemic) in situations such as elective and urgent abdominal aorta surgery and the role that control of this response could represent for the future of vascular surgery.

Bacterial translocation is an important phenomenon in clinical medicine and leads to an increase in patient morbidity and mortality by multiple organ failure. The selectin family plays an important role in the pathogenesis of inflammation, causing an increase in leukocyte-endothelium interactions and inducing a greater leukocyte's migration. This study considered the effect of a sulfo derivative of Sialyl-Lewis(X), GM 1998-016, that will block the P- and E-selectins interaction with a ligand, the Sialyl-Lewis(X), valuing the modulation of the systemic inflammatory response and the induced translocation. Seventy-five Wistar male rats were injected intraperitoneally with Zymosan A and treated with different doses of GM 1998-016 according to study groups. Measurements of values of qualitative and quantitative microbiology, neutrophil infiltration (myeloperoxidase), oxygen free radicals (superoxide anion, superoxide dismutase, catalase, and gluthatione peroxidase), and cytokines (tumor necrosis factor-alpha and interleukin-1beta) were taken at different times after Zymosan administration. A significant decrease of bacterial translocation, both local (MLN) and systemic (p < .05), was observed, with a decrease in the neutrophil infiltration (p < .001), the oxygen free radicals production (p < .01) and the studied cytokines (p < .01). In conclusion, GM 1998-016 showed a protective effect in an in vivo experimental model of bacterial translocation, downregulating the inflammatory response and the leukocyte-endothelium interactions.

Objective: Renal impairment is a very frequent complication of aortic surgery requiring prolonged suprarenal clamping, especially if it is associated with previous hemorrhage. The aim of this study was to assess the beneficial effect of the administration of a nitric oxide (NO) donor on renal function through a modulation of the systemic inflammatory response in a model of abdominal aortic surgery., Methods: Twenty-five minipigs were divided into five groups. Under anesthesia, the animals were subjected to suprarenal aortic-iliac clamping (for 30 minutes) and bypass with a Dacron-collagen prosthetic graft impregnated in rifampicin, with or without associated hemorrhage (40% of total blood volume). Prophylaxis with cefazolin was implemented. The five groups were (1) the sham group (only aortic dissection), (2) the clamping and bypass (C) group, (3) hemorrhage preclamping and bypass (H+C) group, (4) the same as group C but with the administration of the NO donor molsidomine (4 mg/kg intravenously) (C+NO group), (5) the same as the H+C group but with the administration of the NO donor molsidomine (4 mg/kg intravenously) (H+C+NO group). The following were determined: (1) kidney function (serum creatinine), (2) serum cytokines (tumor necrosis factor alpha [TNF-alpha] and interleukin-10 [IL-10]); (3) neutrophil infiltration (myeloperoxidase [MPO]) in the kidney, (4) oxygen free radicals (superoxide anion [SOA] and superoxide dismutase [SOD]) in the kidney, (5) serum nitrites, (6) soluble and kidney tissue cell adhesion molecule (soluble intercellular adhesion molecule-1 [sICAM-1], soluble vascular cell adhesion molecule-1 [sVCAM-1], intercellular adhesion molecule-1 [ICAM-1], and vascular cell adhesion molecule-1 [VCAM-1]), (7) inducible nitric oxide synthase (iNOS) in the kidney, and (8) nuclear factor-kappaB (NF-kappaB) in the kidney. Determinations were made during ischemia at 15 minutes post-reperfusion; at 24, 48, and 72 hours; and on day 7., Results: The different insults used in the experimental model led to deterioration in kidney function and an increase in the systemic (and renal) inflammatory response at all levels investigated. Treatment with an NO donor, both with and without associated hemorrhage, reduced the inflammatory response at the systemic (TNF-alpha and IL-10) and kidney (MPO, SOA, and SOD) levels, normalizing kidney function. Likewise, exogenous administration of NO improved the excessive production of NO (nitrites) via iNOS. This was also reflected in a reduction in CAMs and of NF-kappaB expression. The hypotension induced by molsidomine was transitory and did not elicit hemodynamic repercussions., Conclusion: In our experimental model, prophylactic treatment with the NO donor molsidomine regulates the systemic inflammatory response and minimizes damage at the kidney level. Clinical Relevance The importance of this article resides in the fact that an experimental study that clarifies the effect of the donors of NO under circumstances as similar as possible to those of the human clinic, such as aortic surgery under hypovolemic shock (ruptured aortic aneurysm) have been little studied, most of these studies being performed in rodents without bypass. Using a model with one or two simultaneous insults (aortic clamping with/without previous hemorrhage) that is very similar to the human clinical situation (abdominal aortic rupture), we confirm the findings of previous work related to the beneficial effects of NO donors.

Objective and Design: To evaluate the beneficial effects of exogenous NO and its levels of action in a model of SIRS/Bacterial Translocation (BT) induced by two sequential insults., Material or Subjects: Eighty-six Wistar rats were submitted to different treatments and their tissue and blood samples were accessed at the end of the experiment., Treatment: Nitric Oxide was compared to Gentamicin as the tested guideline for our study., Methods: Dacron graft implantation (first insult) and subsequent administration of Zymosan A((R)) (second insult) were performed in Wistar rats. The animals were divided into 6 groups: I) No manipulation (BASAL: ); II) Laparotomy (L) + mineral oil (SHAM: ); III) L + Graft-Zymosan (GZ) (CONTROL: ); IV) L + GZ + Antibiotic (A) (ASSAY: I); V) L + GZ + NO (ASSAY: II) and VI) L + GZ + A + NO (ASSAY: III). Determinations: Survival, Bacterial Translocation, myeloperoxidase (MPO), Cytokines (TNF-alpha, IL-1beta, IFN-gamma), Oxygen Free Radical (OFR) SOA and detoxifying enzymes (SOD, Superoxide Dismutase, CAT, Catalase and GPX, Glutathione Peroxidase), Cell Adhesion Molecules, CAMs (ICAM-1, VCAM-1 and PECAM-1) and Nuclear Transcription Factor, NFkappaB., Results: The model established induced a mortality rate of 20% and generated BT in all samples. It also significantly increased all variables, with P < 0.001 for MPO and all Cytokines; P < 0.01 for all OFR, and P < 0.05 for CAMs and for NFkappaB. Treatment with A reduced mortality to 0%, significantly decreased BT, MPO, Cytokines and OFR (P < 0.05), but did not reduce CAMs or NFkappaB. NO, either alone or associated, reduced mortality to 0% and abolished BT, significantly decreasing nearly all the variables studied (P < 0.001 for MPO and all Cytokines; P < 0.01 for OFR, and P < 0.05 for CAMs and for NFkappaB)., Conclusions: The exogenous administration of NO before the two sequential insults prevented BT and controlled SIRS peripherally and at both cellular and transcriptional level in a lasting manner. In contrast, antibiotic treatment only exerted its action at peripheral level. The association of both treatments did not provide any important advantages.

Background: Nitric oxide (NO) participates in inflammation and affects almost all steps of its development. Several experimental studies have unveiled the beneficial effects of NO through modulation of the Systemic Inflammatory Response Syndrome (SIRS). In this sense, in the present work we attempted to evaluate the beneficial effects of exogenous NO and its levels of action (biochemical and cellular) in a model of SIRS induced by two sequential insults., Materials and Methods: Dacron graft implantation (first insult) and subsequent administration of Zymosan A (second insult) in Wistar rats. The animals were divided into four groups: 1) No manipulation (Basal); 2) Laparotomy (L) + mineral oil (Sham); 3) L + Graft-Zymosan (GZ) (Control); and 4) L + GZ + NO (Assay). Determinations: Survival, TNF-alpha, SOA, ICAM-1, and NFkappaB., Results: The model established (Control) induced a mortality rate of 20%. Also, it significantly increased the levels of TNF-alpha (P <0.001) and SOA (P <0.01), ICAM-1 expression, and NFkappaB levels (P <0.05). Treatment with NO reduced mortality to 0%, significantly decreasing TNF-alpha (P <0.001) and SOA (P <0.01) levels, ICAM-1 expression, and NFkappaB levels (P <0.05)., Conclusion: The exogenous administration of NO before the two sequential insults controlled SIRS at biochemical level (TNF-alpha, SOA) and at cellular level (transcription) in a lasting manner. The cascade-like interrelationship of both levels and the study design do not allow us the pinpoint the key to its modulation.

Context: Iatrogenic vascular problems due to laparoscopy are a well recognized problem and lead to significant repercussions. In this context, a ten-year review of cases topic is presented, based on experience gained while heading two important vascular surgery services., Cases: Five patients with vascular injuries during elective laparoscopy are described. These patients presented with seven lesions of iliac vessels. All cases were evaluated immediately and required laparotomy, provisional hemostasis and urgent attendance by a vascular surgeon. Direct suturing was performed in three cases. One aortoiliac bypass and one ilioiliac reversed venous graft were made. Venous lesions were sutured. One case of a point-like perforation of the small bowel was found. There were no deaths and no complications during the postoperative period., Discussion: Important points on this subject are made, and advice is given. There needs to be immediate recognition of the vascular injury, and expert repair by a vascular surgeon is recommended, in order to significantly reduce the degree of complications.

The objective of this study was to assess the efficacy, safety, and cost of low-molecular-weight heparin compared to saphenofemoral disconnection for the treatment of internal saphenous proximal thrombophlebitis (SPT). Eighty-four consecutive patients diagnosed as presenting SPT alone (symptoms/echo-Doppler) were divided into 2 comparable groups treated with (1) saphenofemoral disconnection under local anesthesia with a short hospital stay (n = 45) or (2) prospective enoxaparin on an outpatient basis for 4 weeks (n = 39). Informed consent was obtained and inclusion, exclusion, and withdrawal criteria were established. Patients were followed up at 1, 3, and 6 months. Thirty patients per group completed the study requirements. In the disconnection group, 2 patients (6.7%) presented complications of the surgical wound, 1 (3.3%) had SPT recurrence (however, there was no deep venous thrombosis), and 2 (6.7%) had nonfatal pulmonary embolism confirmed by radionuclide scan. In the enoxaparin group, there were 2 cases (6.7%) of minor bleeding (epistaxis and rectal bleeding) and 3 (10%) recurrences of SPT. In the enoxaparin group there was no case of progression of the thrombosis to the deep venous system or pulmonary embolism. The study found no statistically significant differences between saphenofemoral disconnection and enoxaparin in the treatment of SPT, but the low-molecular-weight heparin group had socioeconomic advantages.

Background: The purpose of this work was to evaluate the effect that different antimicrobial agents and different forms of administering them would have over a systemic inflammatory response (SIR) induced by an intraperitoneally implanted collagen-coated Dacron graft., Materials and Methods: Thirty-six male Wistar rats were randomly allocated into six groups of 6 animals each: (I) control, (II) "sham," (III) graft but no antibiotic, (IV) graft plus systemic cefazolin, (V) graft plus locally applied gentamicin, and (VI) graft soaked in rifampicin. After 72 h, mesenteric lymph nodes, liver, kidney, and the implanted graft were sent to the microbiology laboratory and cultured for aerobic and anaerobic organisms in order to evaluate bacterial translocation. Serum cytokines (IL-1beta and TNF-alpha), myeloperoxidase activity in liver and kidney, and superoxide anion and superoxide dismutase activities in liver were also determined to evaluate the level of SIR., Results: Microbiologic and biochemical data indicated that intraperitoneal implantation of a collagen-coated Dacron graft induced a significant (P < 0.05) bacterial translocation and a high inflammatory response, both of which decreased significantly with antibiotic treatment regardless of the means of administration (P < 0.05)., Conclusions: The present experimental model shows that the antibiotics used, in different means of administration, reduce bacterial translocation and behave as modulators of the SIR induced by an intraperitoneal collagen-coated Dacron graft.