Asociación entre metilación del ADN y tabaquismo en pacientes con isquemia crónica amenazante de extremidades inferiores / Association between DNA methylation and smoking in patients with chronic limb-threatening ischemia

Introducción y objetivo: estudiar la asociación entre tabaquismo y el nivel de metilación de dos regiones genómicas en pacientes con enfermedad arterial periférica (EAP). Método: estudio transversal de 297 pacientes (edad media: 69,6 años; varones: 78,5 %) diagnosticados de isquemia crónica de extremidades inferiores en diferentes estadios clínicos entre marzo de 2016 y diciembre de 2019en el servicio de cirugía vascular del Hospital del mar (Barcelona). Se analizó la metilación de Cg02156642 y deCg03636183 asociados en otros estudios al tabaquismo. Se realizó una regresión lineal múltiple para discriminar lasvariables asociadas al nivel de metilación. Se calculó el área bajo la curva ROC para discriminar el nivel de metilaciónentre fumadores y no fumadores. Resultados: de la muestra, 46 pacientes (15,5 %) eran no fumadores; 132 (44,4 %), exfumadores y 119 (40,1 %),fumadores. No se observó una asociación entre la exposición al tabaco y el nivel de metilación del Cg02156642,pero sí con el de Cg03636183: los fumadores presentaban menor nivel de metilación y, además, a más carga detabaco menos metilación (Rho de Spearman: -0,324; p < 0,001).Un nivel de metilación en este CpG del 80 % tiene una sensibilidad (S) del 90,0 % y una especificidad (E) del83,5 % para discriminar entre fumadores y nunca fumadores. Para discriminar entre fumadores y exfumadores,un nivel de metilación del 75 % tiene una S del 69 % y una E del 56,9 %.Al ajustar por todas las variables relacionadas con la metilación, la magnitud de esta asociación entre Cg03636183y tabaquismo se mantenía signifi cativa entre los nunca fumadores y los fumadores. Conclusiones: la metilación del cpg cg03636183 se asocia a tabaquismo en pacientes con eap y está directamenterelacionada con la carga de tabaco. Este biomarcador podría utilizarse en la práctica clínica para valorar el consumode tabaco de nuestros pacientes.(AU)

Introduction and objective: to study the association between smoking and the methylation level of 2 genomicregions in patients with peripheral artery disease (PAD). Method: cross-sectional study of 297 patients (mean age, 69.6 years; males, 78.5%) diagnosed with chronic lowerextremity ischemia at various clinical stages from march 2016 through December 2019 at the Vascular Surgery Unitof Hospital del mar, Barcelona, Catalonia, Spain. methylation analysis of Cg02156642 and Cg03636183, previouslyassociated with smoking in former studies was performed. multiple linear regression was conducted to identifyvariables associated with methylation levels. The area under the ROC curve was estimated to discriminate meth-ylation levels between smokers and non-smokers. Results: among the sample, 46 patients (15.5%) were non-smokers, 132 (44.4%) were former smokers, and 119(40.1%) were current smokers. No association was seen between tobacco exposure and methylation levels ofCg02156642. However, an association was found with Cg03636183: smokers had lower methylation levels, anda higher smoking load was associated with lower methylation (Spearman's Rho, -0.324; p < .001). A methylationlevel of 80% in this region showed a 90.0% sensitivity and an 83.5% specificity to discriminate between smokersand never smokers. To discriminate between smokers and former smokers, a methylation level of 75% had an 69%sensitivity and an 56.9% specificity. After adjusting for all variables associated with methylation, the associationbetween Cg03636183 and smoking remained significant among never smokers and smokers. Conclusions: methylation of the Cg03636183 region is associated with smoking in patients with PAD and is directlyassociated with the smoking load. This biomarker could be used in the routine clinical practice to assess tobaccouse in our patients.(AU)

Bypass distal con vena autóloga invertida / Distal inverted autologous vein bypass

La derivación (bypass) con vena autóloga invertida es, sin lugar a dudas, uno de los procedimientos fundamentales en la revascularización de los miembros isquémicos de las extremidades inferiores. De hecho, fue el primero en desarrollarse (Jean Kunlin). Los autores de este artículo describen su forma tradicional de realizarlo y sus trucos, así como sus maneras de abordar y de evitar problemas, pero lo hacen con un lenguaje práctico (“cómo lo hago”) que ayude a entender el procedimiento a médicos jóvenes en formación. Durante la descripción se mencionan algunas técnicas alternativas, conscientes de que a buen seguro habrá otras y que otros cirujanos lo harán con pequeñas modificaciones.(AU)

The autologous distal vein bypass with an inverted vein is, without doubt, one of the main procedures in the revascularization of ischemic limbs of the lower extremities. In fact, it was the first to be developed (Jean Kunlin). The authors of this article describe their traditional way of doing it, their tricks, their ways of approaching and avoiding problems, but they explain their “how I do it” with a practical language that helps to understand the procedure by young doctors in training. During the description, some technical alternatives are mentioned, aware that there will surely be others and that others vascular surgeons will do so with minor modifi cations.(AU)

Comparison Between Several CT-Derived Psoas Muscle Sarcopenia Markers for Predicting Survival After Abdominal Aortic Aneurysm Repair.

BACKGROUND: Multiple CT-derived measurements of sarcopenia have been described yet their relationship with survival after abdominal aortic aneurysm (AAA) repair has not been properly assessed. We aimed to define and compare the relationship between several psoas CT-derived measurements and the 5-year survival after AAA repair and to evaluate their potential contribution to survival prediction. METHODS: Preoperative CT area (TPA) and density (MTPD) of the psoas muscle at L3 were measured in 218 consecutive AAA patients electively intervened. Additional measurements were obtained by normalizing TPA by anthropometric data or L3-vertebra surface or by TPAxMTPD multiplication (lean psoas muscle area-LPMA). The association of sarcopenia markers with survival was evaluated with Cox models adjusted by age, sex, type of intervention and the Charlson Comorbidity Index, and their contribution to survival prediction assessed with the C-statistic and the Continuous Net Reclassification Index (c-NRI). RESULTS: Sixty patients (27.5%) died during the first 5 years after surgery. There was a statistically significant and linear (spline analysis) relationship of sarcopenia markers with 5-year survival in all multivariate models, except that including LPMA. Despite this association, the inclusion of sarcopenia markers did not improve the C-statistic and moderately increased the c-NRI. None normalized sarcopenia markers performed better than TPA. CONCLUSION: The majority of CT-derived psoas muscle measurements of sarcopenia showed a significant and independent relationship with survival after elective AAA repair. Despite this association, they did not appear to improve sufficiently our survival prediction ability to become an efficient tool for decision-making.

Predictive Value of Complete Blood Count-Derived Inflammatory Markers for 5-Year Survival After Carotid Endarterectomy: Implications for Practice.

Complete blood count inflammatory markers (CBC-IMs) have been associated with cardiovascular diseases and mortality. We aimed to evaluate the relationship between preoperative CBC-IMs and 5-year survival after carotid endarterectomy (CEA). Retrospective analysis of 411 consecutive patients who underwent CEA between 2004 and 2018 was done. CBC-IM included the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte (LMR) ratio, and systemic immune-inflammation index (SII). Survival rate at 5 years was 79.8%. Age (hazard ratio (HR) = 1.05, P = .003), hemoglobin (HR = 0.78, P < .001), heart failure (HR = 2.91, P = .005), American Society of Anesthesiologists (ASA)-IV score (HR = 2.41, P = .043), and active neoplastic disease (HR = 2.61, P = .028) were independently related to survival. The discrimination of this model (C-statistic) was 0.698. Spline analysis showed a linear relationship between survival and NLR (P < .001), PLR (P < .001), and SII (P < .001). After adjusting for the baseline predictive score, there was a significant relationship between survival and NLR (HR = 1.191, P = .001), PLR (HR = 1.004, P = .017), and SII (HR = 1.001, P < .001). The addition of NLR, PLR, and SII to the survival model improved the continuous net reclassification index (c-NRI) by 0.29 (P = .028), 0.347 (P = .008), and 0.481 (P < .001), respectively, but not the C-statistic. CBC-IMs show a linear and independent relationship with 5-year survival after CEA and may moderately contribute to patient selection for this preventive intervention.

Usefulness of red cell distribution width to predict mortality in patients undergoing endovascular repair of abdominal aortic aneurysms.

BACKGROUND: Red cell distribution width (RDW) reflecting impaired erythropoyesis, has been associated with poor prognosis and mortality in several conditions. The aim of this study was to determine the relationship between RDW and the 5-year survival after the endovascular repair of abdominal aortic aneurysms (EVAR) and its ability to improve the discriminative power of a survival predictive score. METHODS: Retrospective analysis of 284 patients undergoing EVAR at a single centre. The pattern of relationship between RDW and survival was assessed with penalized smoothing splines. Categorized RDW values were added to a predictive score based in standard preoperative variables, whose improvement in discriminative power was calculated on the basis of changes in the C-statistics and the continuous Net Reclassification Index (c-NRI). RESULTS: The survival rate at 5 years was 66.2% and was independently associated with hemoglobin (HR=0.85, P<0.004), statin intake (HR=0.54, P<0.004), heart failure (HR=2.53, P<0.018), atrial fibrillation (HR=2.53, P<0.000) and the non-revascularized coronary artery disease (HR=2.15, P<0.005). The relationship between RDW values and 5-year survival was linear. RDW-CV and RDW-SD were categorized to cut-off values of ≥15% (N.=83, 29.2%) and ≥50 fL (N.=82, 28.9%) that were independently associated with poorer 5-year survival rates (HR=2.03, CI 95%=1.29-3.19, P=0.002 and HR=1.89, CI 95%=1.21-2.95, P=0.005, respectively). The addition of the RDW CV or the RDW-SD to the baseline predictive score significantly improved the c-NRI (0.437, P<0.001 and 0.442, P<0.001, respectively). CONCLUSIONS: High preoperative RDW levels were linear and adversely related to 5-year survival after EVAR, improved the discriminative power of a predictive score based in standard preoperative variables and may help in decision-making at the time of surgical planning.

Historia natural del paciente sometido a una amputación infracondílea: análisis de la supervivencia y protetización durante 2 décadas / Natural History After Below-knee Amputation: Analysis of Survival and Prosthetic Fitting Over 2 Decades

INTRODUCCIÓN: El objetivo de este estudio es conocer la historia natural de los pacientes sometidos a una amputación infracondílea (AIC) y comparar su evolución a lo largo de 2 décadas, así como los factores predictores de supervivencia, protetización, y amputación contralateral. MÉTODOS: Estudio retrospectivo de 209 pacientes consecutivos (edad media 72,9 años, varones 67,9%) sometidos a AIC a lo largo de 2 periodos: 1996-2005 y 2006-2015. Se valoró mediante análisis de supervivencia la protetización, el riesgo de amputación contralateral y la supervivencia, así como sus factores predictores. RESULTADOS: Se realizaron 133 AIC en el 1996-2005 y 106 en el 2006-2015. La etiología global que motivó la AIC fue por isquemia aguda (4,3%), crónica (34%), infección (9,1%) o mixta (crónica+infección, 52,6%), sin diferencias entre periodos. Se incrementaron las revascularizaciones previas entre ambas décadas del 31,6 al 54,3%. Supervivencia: mortalidad a un mes = 9,2%; un año = 31,9%; 2 años = 43,8% y 5 años = 63,9%, sin diferencias significativas entre ambos periodos. Protetización: tasa de protetización global del 44,5% durante todo el seguimiento, sin diferencias significativas entre ambos periodos. Lograron deambular el 41,1% de los pacientes. Amputación contralateral: El 20,1% de los pacientes requirieron posteriormente una amputación mayor contralateral, sin hallar diferencias significativas entre ambos periodos. CONCLUSIONES: En la última década han disminuido las AIC probablemente por un incremento del intervencionismo de revascularización previo. A pesar de ello, no se modificaron los resultados de protetización, amputación contralateral o supervivencia. En cualquier caso, el número de pacientes que llegan a alcanzar la deambulación es modesto, por lo que se subraya la necesidad de una óptima selección del paciente tributario a AIC con el objetivo de protetizarse

INTRODUCTION: This study sought to evaluate the natural history of patients undergoing below-knee amputation (BKA) and compare their evolution over 2 decades, as well as survival predictors, prosthetic fitting, and contralateral amputation. METHODS: Retrospective study of 209 consecutive patients (mean age 72.9 years; 68% males) who underwent BKA in 2 periods: 1996-2005 and 2006-2015. The fitting of prostheses, risk of contralateral amputation and survival, as well as their predictive factors, were assessed by survival analysis. RESULTS: 133 BKA were performed from 1996-2005 and 106 from 2006-2015. The etiology that motivated the BKA was acute ischemia (4.3%), chronic ischemia (34.0%), infection (9.1%) or mixed (chronic+infection, 52.6%), with no differences found between periods. Survival: mortality within one month = 9.2%, one year = 31.9%, 2 years = 43.8% and 5 years = 63.9%, with no significant differences between the 2 periods. Prosthetic: the fitting rate was 44.5% throughout the follow-up, with no significant differences between the two periods. 41.1% patients managed to walk. Contralateral amputation: 20.1% of the patients later required a major contralateral amputation, with no significant differences between the two periods. CONCLUSIONS: In the last decade, fewer BKA have been performed probably, due to higher previous interventional revascularization. Despite this, the results of fitting, contralateral amputation or survival were not modified. In any case, the number of patients who are able to achieve ambulation is modest, so it emphasizes the need for an optimal selection of patients with BKA with the goal of prosthetic fitting

Natural History After Below-knee Amputation: Analysis of Survival and Prosthetic Fitting Over 2 Decades. / Historia natural del paciente sometido a una amputación infracondílea: análisis de la supervivencia y protetización durante 2 décadas.

INTRODUCTION: This study sought to evaluate the natural history of patients undergoing below-knee amputation (BKA) and compare their evolution over 2 decades, as well as survival predictors, prosthetic fitting, and contralateral amputation. METHODS: Retrospective study of 209 consecutive patients (mean age 72.9 years; 68% males) who underwent BKA in 2 periods: 1996-2005 and 2006-2015. The fitting of prostheses, risk of contralateral amputation and survival, as well as their predictive factors, were assessed by survival analysis. RESULTS: 133 BKA were performed from 1996-2005 and 106 from 2006-2015. The etiology that motivated the BKA was acute ischemia (4.3%), chronic ischemia (34.0%), infection (9.1%) or mixed (chronic+infection, 52.6%), with no differences found between periods. Survival: mortality within one month=9.2%, one year=31.9%, 2 years=43.8% and 5 years=63.9%, with no significant differences between the 2 periods. Prosthetic: the fitting rate was 44.5% throughout the follow-up, with no significant differences between the two periods. 41.1% patients managed to walk. Contralateral amputation: 20.1% of the patients later required a major contralateral amputation, with no significant differences between the two periods. CONCLUSIONS: In the last decade, fewer BKA have been performed probably, due to higher previous interventional revascularization. Despite this, the results of fitting, contralateral amputation or survival were not modified. In any case, the number of patients who are able to achieve ambulation is modest, so it emphasizes the need for an optimal selection of patients with BKA with the goal of prosthetic fitting.

Disease Progression in the Contralateral Carotid Artery is Still Common After Endarterectomy.

BACKGROUND: Disease progression in the contralateral carotid artery (CA) after a carotid endarterectomy (CEA) was common in the past. Current medication regimens for these patients are better and have probably modified this progression. We evaluated the rate of disease progression in the contralateral CA over the last decade. METHODS: A retrospective analysis of 291 consecutive patients undergoing a CEA between 2005 and 2014 was performed. Disease progression in the contralateral CA after CEA was determined by a duplex ultrasound. Statistics were calculated by Kaplan-Meier life-tables and Cox regression. RESULTS: Of the 291 patients, 246 (84.5%) received at baseline antiplatelet and/or anticoagulant agents, and 223 (77%) received statins. These proportions increased over the second half of the study. Disease progression in the contralateral CA was evaluated in 200 patients during a mean follow-up of 3.5 years. Progression-free survival rates from any disease progression at 1 and 5 years were of 89.3% and 68.6%, respectively. Free survival rates from <50% to >50% progression or from 50% to 69% to a higher category at 1 and 5 years were of 89.3% and 75.5%, respectively. Finally progression-free survival rates to a >70% stenosis or occlusion at 1 and 5 years were of 96.8% and 90.1%, respectively. Age (hazard ratio = 1.034, P = 0.048) and dyslipidemia (hazard ratio = 1.93, P = 0.045) were also associated with any disease progression. CONCLUSIONS: Current rates of disease progression in the contralateral CA after CEA are similar to those reported more than 1 decade ago. Further research will be needed to evaluate the impact of current medical regimens at these stages of disease.

Long-term Survival after Carotid Endarterectomy in a Population with a Low Coronary Heart Disease Fatality: Implications for Decision Making.

BACKGROUND: According to the current guidelines, long-term survival is an important factor influencing decision making in patients with severe asymptomatic carotid stenosis. Nevertheless, data are lacking for populations with a low incidence of coronary heart disease, the main cause of death among these patients. We aimed to assess the long-term survival after carotid endarterectomy (CEA) in a Mediterranean hospital. METHODS: Retrospective analysis was conducted of 291 consecutive patients (main age 69 years, 78.7% men) who underwent a CEA for symptomatic (n = 147, 50.5%) or asymptomatic (n = 144, 49.5%) carotid stenosis in 2005-2014 at the Hospital del Mar (Barcelona, Spain). A Kaplan-Meier life table was done and a multivariable Cox regression model was built for the analysis of the long-term survival-associated risk factors. RESULTS: The immediate combined mortality and/or neurological morbidity rate was 2.7%. The mean follow-up was 55 months (complete in 99.7%). During follow-up 62 patients (21.3%) died, being cancer the most frequent cause (35.5%). Cumulative 3- and 5-year survival rates were 89% and 81%, respectively. Independent risk factors (Cox regression) related to survival included age (hazards ratio [HR] 1.09, P < 0.001), an American Society of Anesthesiologists class IV score (HR 4.04, P = 0.015), and the preoperative hemoglobin value (HR 0.73, P < 0.001). The discrimination of the resulting model was 0.719 (95% confidence interval 0.644-0.794). Previous symptomatic carotid stenosis was not related to long-term survival. CONCLUSIONS: The long-term survival of patients submitted to CEA in our series lies in the lower limit of the estimated range by other groups and is markedly related to cancer. Our study suggests that predictive models for survival are influenced by regional characteristics.

Survival After Endovascular Abdominal Aortic Aneurysm Repair in a Population with a Low Incidence of Coronary Artery Disease.

BACKGROUND: Endovascular aortic aneurysm repair (EVAR) is a prophylactic procedure, so the decision to operate should consider, as recent guidelines suggest, the life expectancy of the patient. Several models for predicting life span have been already designed, but little is known about how intervened patients evolve in Southern European Countries, where the incidence of coronary artery disease, the main cause of death among these subjects, is low. METHODS: We conducted a retrospective analysis of 176 consecutive patients who underwent elective EVAR at the Vascular Surgery Department of the Hospital del Mar (Barcelona, Spain) during 2000-2014. Cox regressions were performed to identify preoperative factors associated with long-term survival after EVAR, and a risk model was developed. RESULTS: Three- and five-year survival rates were 73.9 and 53.9 %, respectively. During the follow-up, 72 deaths (40.9 %) were registered, cancer being the most frequent cause (41.7 %). Preoperative variables negatively associated with long-term survival were serum creatinine ≥ 150 µmol/L (HR 2.5; 95 % CI 1.4-4.2), chronic obstructive pulmonary disease (HR 1.9; 95 % CI 1.2-3.1), atrial fibrillation (HR 2.0; 95 % CI 1.2-3.4), and prior cancer history (HR 1.9; 95 % CI 1.2-3.1). Distal pulses present in both lower limbs were marginally associated with survival (HR 0.65; 95 % CI 0.4-1.07). The survival predictive model showed a good discrimination capacity (C statistic = 0.703; 95 % CI 0.641-0.765). CONCLUSIONS: Long-term survival of patients submitted to EVAR in our setting was worse than expected and markedly related to cancer. Our study suggests that predictive models for long-term survival after EVAR may be influenced by regional characteristics of the intervened population. This effect should be taken in consideration in the decision-making process of these patients.