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)

A cost-effectiveness analysis of the introduction of a specialised consultation with duplex ultrasound assessment prior to vascular access surgery for haemodialysis.

INTRODUCTION: Duplex ultrasound (DUS) is increasingly used before vascular access (VA) surgery for haemodialysis. However, the cost-effectiveness of this approach is unknown. Our objective was to assess whether the introduction of a specialised consultation with DUS assessment modifies the cost and the time delay to achieve a first VA valid for haemodialysis. PATIENTS AND METHODS: Prospective cohort of patients undergoing a first VA (June 2014-July 2017) after a specialised consultation with DUS (ECO group). They were compared with a historical cohort (January 2012-May 2014) where VA was indicated exclusively by clinical evaluation (CLN group). We analysed the cost related to visits, DUS assessments, interventions, hospital admissions and graft materials to achieve a first VA valid for haemodialysis at least during 1 month. RESULTS: 86 patients in the CLN group were compared with 92 in the ECO group. Patients in the ECO group were younger (68.4 vs. 64.0 years; P=.038) but no other differences were seen among groups. The average cost to achieve a first AV valid for haemodialysis was significantly lower in the ECO group (2707 vs. 3347€; P=.024). There was a higher cost associated with DUS assessments in the ECO group yet the CLN group had a higher cost related to follow-up visits, successive surgical interventions, prosthetic material, days of hospital admission and catheters. The mean time needed to achieve a first AV valid for haemodialysis was also shorter in the ECO group (49.9 vs. 82.9 days, P=.002). CONCLUSION: The introduction of a specialised vascular access consultation with DUS prior to VA surgery has reduced the cost necessary to achieve a first VA valid for haemodialysis. From the patient's point of view this has meant less interventions and hospital admissions and a shortening of the time delay.

Impacto de la introducción de una consulta específica con valoración eco-doppler en el costo asociado a la obtención de un primer acceso vascular para hemodiálisis / A cost-effectiveness analysis of the introduction of a specialised consultation with duplex ultrasound assessment prior to vascular access surgery for haemodialysis

Introducción: La valoración mediante eco-doppler (ED) previa a la realización de un acceso vascular (AV) está cada vez más extendida, pero existen pocos estudios que aborden su coste/efectividad. Nuestro objetivo fue evaluar si la introducción de una consulta específica de AV con ED modifica el coste, los tiempos de demora, el número de re-intervenciones e ingresos para lograr un primer AV útil.Pacientes y métodosCohorte prospectiva de pacientes sometidos a un primer AV (junio 2014-julio 2017), a quienes se practicó un ED preoperatorio (grupo ECO). Se compararon con una cohorte histórica (enero 2012-mayo 2014) de primeros AV indicados exclusivamente mediante valoración clínica (grupo CLN). Se calcularon los costes de realización y el seguimiento para lograr un AV útil para hemodiálisis durante como mínimo un mes sin complicaciones.ResultadosSe compararon 86 pacientes del grupo CLN con 92 del ECO, siendo estos últimos más jóvenes (68,4 vs. 64,0 años; p=0,038). El coste medio del grupo ECO fue significativamente inferior (ECO=2.707 vs. CLN=3.347€; p=0,024). El grupo ECO tuvo un coste mayor en ecografías preoperatorias y de seguimiento. El grupo CLN tuvo un coste superior respecto a consultas de seguimiento, intervenciones quirúrgicas sucesivas, material protésico, días de ingreso y catéteres. Se disminuyó el tiempo de demora para la realización del AV (CLN=82,9 vs. ECO=49,9 días; p=0,002).ConclusiónLa introducción de una consulta específica de AV para hemodiálisis con valoración ED, ha permitido disminuir el coste para lograr un primer AV útil, como consecuencia de una reducción en los tiempos de demora, visitas de control, re-intervenciones, días de ingreso e implantación de catéteres. (AU)

Introduction: Duplex ultrasound (DUS) is increasingly used before vascular access (VA) surgery for haemodialysis. However, the cost-effectiveness of this approach is unknown. Our objective was to assess whether the introduction of a specialised consultation with DUS assessment modifies the cost and the time delay to achieve a first VA valid for haemodialysis.Patients and methodsProspective cohort of patients undergoing a first VA (June 2014-July 2017) after a specialised consultation with DUS (ECO group). They were compared with a historical cohort (January 2012-May 2014) where VA was indicated exclusively by clinical evaluation (CLN group). We analysed the cost related to visits, DUS assessments, interventions, hospital admissions and graft materials to achieve a first VA valid for haemodialysis at least during 1 month.ResultsEighty-six patients in the CLN group were compared with 92 in the ECO group. Patients in the ECO group were younger (68.4 vs. 64.0 years; P=.038) but no other differences were seen among groups. The average cost to achieve a first AV valid for haemodialysis was significantly lower in the ECO group (2707 vs. 3347€; P=.024). There was a higher cost associated with DUS assessments in the ECO group yet the CLN group had a higher cost related to follow-up visits, successive surgical interventions, prosthetic material, days of hospital admission and catheters. The mean time needed to achieve a first AV valid for haemodialysis was also shorter in the ECO group (49.9 vs. 82.9 days, P=.002).ConclusionThe introduction of a specialised vascular access consultation with DUS prior to VA surgery has reduced the cost necessary to achieve a first VA valid for haemodialysis. From the patient's point of view this has meant less interventions and hospital admissions and a shortening of the time delay. (AU)

A cost-effectiveness analysis of the introduction of a specialised consultation with duplex ultrasound assessment prior to vascular access surgery for haemodialysis. / Impacto de la introducción de una consulta específica con valoración eco-doppler en el costo asociado a la obtención de un primer acceso vascular para hemodiálisis.

INTRODUCTION: Duplex ultrasound (DUS) is increasingly used before vascular access (VA) surgery for haemodialysis. However, the cost-effectiveness of this approach is unknown. Our objective was to assess whether the introduction of a specialised consultation with DUS assessment modifies the cost and the time delay to achieve a first VA valid for haemodialysis. PATIENTS AND METHODS: Prospective cohort of patients undergoing a first VA (June 2014-July 2017) after a specialised consultation with DUS (ECO group). They were compared with a historical cohort (January 2012-May 2014) where VA was indicated exclusively by clinical evaluation (CLN group). We analysed the cost related to visits, DUS assessments, interventions, hospital admissions and graft materials to achieve a first VA valid for haemodialysis at least during 1 month. RESULTS: Eighty-six patients in the CLN group were compared with 92 in the ECO group. Patients in the ECO group were younger (68.4 vs. 64.0 years; P=.038) but no other differences were seen among groups. The average cost to achieve a first AV valid for haemodialysis was significantly lower in the ECO group (2707 vs. 3347€; P=.024). There was a higher cost associated with DUS assessments in the ECO group yet the CLN group had a higher cost related to follow-up visits, successive surgical interventions, prosthetic material, days of hospital admission and catheters. The mean time needed to achieve a first AV valid for haemodialysis was also shorter in the ECO group (49.9 vs. 82.9 days, P=.002). CONCLUSION: The introduction of a specialised vascular access consultation with DUS prior to VA surgery has reduced the cost necessary to achieve a first VA valid for haemodialysis. From the patient's point of view this has meant less interventions and hospital admissions and a shortening of the time delay.

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.

Utilidad de la valoración ecográfica previa a la realización del primer acceso vascular para hemodiálisis / Utility of doppler ultrasound in the preoperative evaluation of the first vascular access for haemodialysis

INTRODUCCIÓN: Tradicionalmente la indicación del tipo de acceso vascular (AV) se ha basado en la exploración física del cirujano, pero actualmente se sugiere que los métodos de imagen podrían aportar un beneficio. Nuestro objetivo fue valorar si el eco-doppler preoperatorio modifica los resultados del primer AV para hemodiálisis. PACIENTES Y MÉTODOS: Cohorte prospectiva de pacientes sometidos a un primer AV entre junio de 2014 y julio de 2017, a quienes se practicó un eco-doppler preoperatorio (grupo ECO). Se compararon con una cohorte histórica (enero de 2012-mayo de 2014) de primeros AV indicados exclusivamente mediante clínica (grupo CLN). RESULTADOS: Se compararon 86 pacientes del grupo CLN con 92 del ECO, siendo estos últimos más jóvenes (68,4 vs 64,0 años; p = 0,038). Las permeabilidades primarias (CLN/ECO) a 1 y 2 años fueron del 59,5/71,9% y del 53,1/57,8%, marginalmente mejores en el grupo ECO (p = 0,057). Las permeabilidades asistidas a 1 y 2años fueron del 63,2/80,7% y del 58,1/70,2%, siendo significativamente mejores para el grupo ECO (p = 0,010). Requirieron un nuevo AV durante los primeros 6 meses, por falta de permeabilidad/utilidad del inicial, el 26,7% en el grupo CLN y el 7,6% en el ECO (p < 0,001). Se realizaron una media de 1,39 intervenciones para conseguir un AV útil en el grupo CLN y 1,08 en ECO (p = 0,001), siendo el primer AV útil a nivel radiocefálico en el 31,0/45,1% (p = 0,039). CONCLUSIÓN: La indicación del primer AV en función de una exploración mediante eco-doppler preoperatoria podría mejorar de forma significativa la permeabilidad, disminuir la necesidad de nuevos AV y permitir realizarlos más distales

INTRODUCTION: Traditionally, the indication of the type of vascular access (VA) has been based on the surgeon's physical examination, but it is now suggested that imaging methods could provide a clinical benefit. Our aim was to determine whether or not preoperative Doppler ultrasound modifies outcomes of the first VA for haemodialysis. PATIENTS AND METHODS: Prospective cohort of patients undergoing a first VA from June 2014 to July 2017 who had a preoperative Doppler ultrasound (ECO group). They were compared to a historical cohort (January 2012-May 2014) of first VA indicated exclusively by clinical assessment (CLN group). RESULTS: A total of 86 patients from the CLN group were compared to 92 from the ECO group, which was younger (68.4 vs 64.0, P = .038). The primary patency (CLN/ECO) at 1 and 2 years was 59.5%/71.9% and 53.1%/57.8% respectively, marginally better in the ECO group (P = .057). The assisted patency at 1 and 2 years was 63.2%/80.7% and 58.1%/70.2%, respectively, significantly better for the ECO group (P = .010). Due to lack of patency/utility of the initial VA, 26.7% in the CLN group and 7.6% in the ECO group (P <.001) required a new VA during the first 6months. An average of 1.39 interventions were performed to achieve a useful VA in the CLN group and 1.08 in the ECO group (P < .001), the first VA being useful at the radiocephalic level in 31.0%/45.1% (P = .039). CONCLUSION: The indication of the first VA according to a preoperative Doppler ultrasound examination could decrease the need for new VA, enable them to be made more distal, and significantly improve patency

Utility of doppler ultrasound in the preoperative evaluation of the first vascular access for haemodialysis. / Utilidad de la valoración ecográfica previa a la realización del primer acceso vascular para hemodiálisis.

INTRODUCTION: Traditionally, the indication of the type of vascular access (VA) has been based on the surgeon's physical examination, but it is now suggested that imaging methods could provide a clinical benefit. Our aim was to determine whether or not preoperative Doppler ultrasound modifies outcomes of the first VA for haemodialysis. PATIENTS AND METHODS: Prospective cohort of patients undergoing a first VA from June 2014 to July 2017 who had a preoperative Doppler ultrasound (ECO group). They were compared to a historical cohort (January 2012-May 2014) of first VA indicated exclusively by clinical assessment (CLN group). RESULTS: A total of 86 patients from the CLN group were compared to 92 from the ECO group, which was younger (68.4 vs 64.0, P=.038). The primary patency (CLN/ECO) at 1 and 2years was 59.5%/71.9% and 53.1%/57.8% respectively, marginally better in the ECO group (P=.057). The assisted patency at 1 and 2years was 63.2%/80.7% and 58.1%/70.2%, respectively, significantly better for the ECO group (P=.010). Due to lack of patency/utility of the initial VA, 26.7% in the CLN group and 7.6% in the ECO group (P<.001) required a new VA during the first 6months. An average of 1.39 interventions were performed to achieve a useful VA in the CLN group and 1.08 in the ECO group (P<.001), the first VA being useful at the radiocephalic level in 31.0%/45.1% (P=.039). CONCLUSION: The indication of the first VA according to a preoperative Doppler ultrasound examination could decrease the need for new VA, enable them to be made more distal, and significantly improve patency.