Aplicabilitat de les corbes CUSUM en el control de qualitat i en l'avaluació d'efectes d'aprenentatge en cirurgia endovascular

Premi Extraordinari de Doctorat concedit pels programes de doctorat de la UAB per curs acadèmic 2017-2018El control de qualitat terapèutica i el monitoratge de l'efecte d'aprenentatge constitueixen dues responsabilitats ineludibles durant l'adquisició i manteniment de noves modalitats terapèutiques. Les corbes CUSUM han estat utilitzades amb èxit per aquests dos propòsits. L'objectiu d'aquest estudi va ser avaluar la qualitat terapèutica i l'efecte d'aprenentatge a partir de les corbes CUSUM, associats a la introducció i desenvolupament de procediments endovasculars amb intenció de tractar en els territoris aorto-ilíac, fèmoro-popliti i renal, així com l'avaluació de l'eficàcia i seguretat dels procediments endovasculars diagnòstics i terapèutics realitzats a través d'un abordatge transhumeral. MATERIAL I MÈTODES: En primer lloc, pacients consecutius afectes d'arteriopatia obliterant aorto-ilíaca, fémoro-poplítia o renal amb indicació terapèutica endovascular, tractats per cirurgians vasculars a l'Hospital del Mar de Barcelona entre els anys 2003 i 2009, sobre els quals es varen registrar com a indicadors de qualitat la iatrogènia, la no consecució tècnica i el fracàs tècnic durant el primer mes. En segon lloc, pacients consecutius en els quals es van realitzar procediments endovasculars per punció humeral, tractats per cirurgians vasculars a l'Hospital del Mar entre els anys 2003 i 2010, sobre els quals es varen registrar com a indicadors de qualitat les complicacions aparegudes durant els procediments. Es van traslladar les dades a corbes CUSUM ajustades per la morbilitat mitja publicada per cada territori i pels abordatges humerals i les inflexions ascendents de les gràfiques varen ser avaluades posteriorment mitjançant subanàlisis per cada indicador de qualitat i proves Chi quadrat. RESULTATS: Durant el període 2003-2009 es van tractar 553 pacients, dels quals, 131 (23,7%) presentaven malaltia oclusiva aorto-ilíaca, 142 (25,7%) fémoro-poplítia i 128 (23,1%) renal. Es van practicar, respectivament, 3 PTA (angioplàstia transluminal percutània) simples i 117 PTA + stent; 8 PTA simples i 119 PTA + stent i 19 PTA simples i 109 PTA + stent. Els percentatges associats a iatrogènia varen ser 14,5%, 9,2% i 1,6%, de no consecució tècnica 6,9%, 10,6% i 1,6%, i de fracàs tècnic durant el primer mes 0,8%, 4,9% i 2,3%, respectivament. Les corbes CUSUM d'angioplàstia ilíaca varen mostrar dues inflexions ascendents a l'inici i al final del període, condicionades en ambdós casos per iatrogènia (p=0,034) i l'última, a més, per no consecució tècnica (p=0,033). Les corbes CUSUM d'angioplàstia fémoro-poplítia varen mostrar una inflexió ascendent progressiva en tot el període analitzat, atribuïble inicialment a iatrogènia i posteriorment a no consecució tècnica (p=0,05). Les corbes CUSUM d'angioplàstia renal no varen mostrar cap inflexió ascendent al llarg de tot el període. Pel que fa als procediments realitzats via transhumeral, tots excepte un cas van poder ser duts a terme d'acord amb la seva intenció inicial. La taxa global de complicacions va ser d'un 5,5% (5 pseudoaneurismes (2,1%), 4 accidents isquèmics transitoris (1,7%), 3 trombosis d'artèria humeral (1,3%) i 1 tamponament cardíac (0,4%)). En 4 d'aquests pacients va ser necessària una reparació quirúrgica oberta (30,8%). No es van observar diferències estadísticament significatives en relació a edat o sexe del pacient. Les corbes CUSUM creades per un risc teòric del 2% van mostrar 2 inflexions positives estadísticament significatives: una a la fase inicial de la sèrie associada a procediments diagnòstics (p=0,043) i una segona a la fase final de la sèrie associada a procediments terapèutics (p=0,018). CONCLUSIÓ: Les corbes CUSUM constitueixen un excel·lent sistema d'avaluació de la qualitat terapèutica que s'ofereix als nostres pacients en la introducció i desenvolupament de tècniques endovasculars. Els subanàlisis per a cada indicador de qualitat permeten identificar les causes atribuïbles a cada inflexió ascendentQuality of care and learning effect surveillance are two unavoidable responsibilities during acquirement and maintenance of new therapeutic techniques. CUSUM curves methodology have been successfully used for these two purposes. The aim of this study was to evaluate, applying CUSUM curves, the quality of care and the learning effect, associated with the introduction and development of intention to treat endovascular procedures in aorto-iliac, femoropopliteal and renal artery occlusive disease, as well as evaluating, the efficacy and safety of the endovascular diagnostic and therapeutic procedures performed through a brachial approach. MATERIAL AND METHODS: Firstly, consecutive patients with aorto-iliac, femoropopliteal or renal artery occlusive disease with endovascular therapeutic indication, treated by vascular surgeons in the Hospital del Mar of Barcelona between 2003 and 2009, of those were registered, as quality indicators, inability to cross the lesion, peri- and post-procedural complications and significant residual stenosis or occlusion at 1 month. Secondly, consecutive patients in which endovascular procedures through a brachial approach were performed, treated by vascular surgeons in the Hospital del Mar of Barcelona between 2003 and 2010, of those were registered, as quality indicators, all procedural complications. Data collected were transferred to adjusted CUSUM curves according to the average published morbidity given for each arterial territory and for brachial approach. Graphic ascending inflections were later evaluated with sub analysis for each quality indicator and Chi test. RESULTS: Between 2003-2009, 553 consecutive patients, scheduled for endovascular intervention of aorto-iliac (n = 131, 23.7%), femoropopliteal (n = 142, 25.7%) and renal artery (n = 128, 23.1%) occlusive disease were treated. 3 PTA (percutaneous transluminal angioplasty) and 117 PTA + stent; 8 PTA and 119 PTA + stent and 109 PTA + stent, were respectively performed. The percentages associated with peri- and post-procedural complications were 14.5%, 9.2% and 1.6%; failure to cross the lesion, 6.9%, 10.6% and 1.6%; and significant residual stenosis or occlusion at 1 month, 0.8%, 4.9% and 2.3%, respectively. Aorto-iliac CUSUM curve showed two upward inflections at the beginning and the end of the period, both associated with peri- and post-procedural complications (p = 0.034) and the last one also due to failure to cross the lesion (p = 0.033). Femoro-popliteal CUSUM curve moved progressively upward during all the period, initially related to peri- and post-procedural complications and later to failure to cross the lesion (p = 0.005). Renal CUSUM curve didn't show any upward inflection during the analysed period. When it comes to the procedures performed via brachial approach, all but one procedure were completed according to their scheduled intention. The overall complication rate was 5.5% (5 pseudoaneurysms (2.1%), 4 transient ischemic attack (1.7%), 3 brachial artery thromboses (1.3%) and 1 cardiac tamponade (0.4%). Surgical intervention was required in four of these patients (30.8%). No significant differences were observed according to age or sex. CUSUM curves created at a 2% theoretical risk showed two statistically significant upward inflections: one early in the series associated with diagnostic procedures (p=0.043) and another at the end of the study related to therapeutic interventions (p=0.018). CONCLUSION: CUSUM curves constitute an excellent tool for evaluating the quality of care provided to our patients during the introduction and development of endovascular techniques. Quality indicator sub analysis allows us to identify the causes attributable to every upward inflection of the curve

Endovascular treatment of a splenic vein aneurysm through a transhepatic approach

Aneurysms of the portal vein and its branches have been rarely described. Their natural history is unknown although large ones (>3 cm in diameter) have been reported to cause rupture, thrombosis, duodenal or biliary obstruction, inferior vena cava compression and/or portal hypertension. We report the case of an incidentally diagnosed 4.5 cm splenic vein aneurysm repaired by endovascular treatment through a transhepatic route. The aneurysm was successfully excluded using a covered stent (Viabahn, Gore). The transhepatic route opens the possibility of offering a minimally invasive approach to vascular lesions of the portal vein system. Splenic vein aneurysms were first reported in 1953 (1) and they are part of the extrahepatic portal vein aneurysm group (2). Their mechanism of development is not well understood. Etiology may include congenital causes (inherent weakness of the vessel wall) or acquired causes (trauma, inflammation such as pancreatitis, liver disease, or portal hypertension). However, portal aneurysms do not seem to be the result of an isolated portal hypertension since they are extremely rare even in patients with this condition (3). The demographic characteristics of extrahepatic portal vein aneurysm include a female-to-male ratio of 2:1 and the median age of 52 years (range, 5–77 years). The size of the reported aneurysms ranges from 1.9 to 8 cm. The most common location of the aneurysm is in the main portal vein trunk, the junction of the superior mesenteric vein and the splenic vein, or at the hepatic hilus; intrahepatic venous aneurysms are rare (4, 5). Here, for the first time, we report the successful endovascular treatment of a splenic vein aneurysm through transhepatic percutaneous approach using a Viabahn stent

L'ús de la metodologia CUSUM pel control de qualitat i de l'efecte d'aprenentatge en els procediments endovasculars

El control de qualitat terapèutica i el monitoratge de l'efecte d'aprenentatge constitueixen dues responsabilitats ineludibles durant l'adquisició i manteniment de noves modalitats terapèutiques. L'objectiu d'aquest estudi va ser avaluar qualitat terapèutica i efecte d'aprenentatge a partir de corbes CUSUM, associats a la introducció i desenvolupament de procediments endovasculars incloent 553 pacients consecutius amb arteriopatia obliterant aorto-ilíaca, fémoro-poplítia o renal, tractats per cirurgians vasculars a l'Hospital del Mar entre 2003-2009, registrant-ne iatrogènia, no consecució tècnica i fracàs tècnic durant el primer mes i realitzant corbes CUSUM per a cada territori, que han acabat constituint un excel·lent sistema d'avaluació de qualitat terapèutica

Differential expression analyses on aortic tissue reveal novel genes and pathways associated with abdominal aortic aneurysm onset and progression

Background Abdominal aortic aneurysms (AAA) are focal dilatations of the abdominal aorta. They are normally asymptomatic and progressively expand, increasing their risk of rupture. Rupture of an AAA is associated with high mortality rates, but the mechanisms underlying the initiation, expansion and rupture of AAA are not yet fully understood. This study aims to characterize and identify new genes associated with the pathophysiology of AAA through differential expression analyses between dilated and non-dilated aortic tissue samples, and between AAA of different diameters. Our study used RNA-seq data on 140 samples, becoming the largest RNA-seq dataset for differential expression studies of AAA.Results We identified 7,454 differentially expressed genes (DEGs) between AAA and controls, 2,851 of which were new compared to previous microarray studies. Notably, a novel cluster on adenosine triphosphate synthesis regulation emerged as strongly associated with AAA. Additionally, exploring AAA of different diameters identified eight genes (EXTL3, ZFR, DUSP8, DISP1, USP33, VPS37C, ZNF784, RFX1) that overlapped with the DEGs between AAA and controls, implying roles in both disease onset and progression. Seven genes (SPP1, FHL1, GNAS, MORF4L2, HMGN1, ARL1, RNASE4) with differential splicing patterns were also DEGs between AAA and controls, suggesting that splicing differences contribute to the observed expression changes and the disease development.Conclusions This study identified new genes and pathways associated with AAA onset and progression and validated previous relevant roles of inflammation and intracellular calcium regulation. These findings provide insights into the complex mechanisms underlying AAA and indicate potential targets to limit AAA progression and mortality risk

Aplicabilitat de les corbes cusum en el control de qualitat i en l’avaluació d’efectes d’aprenentatge en cirurgia endovascular

El control de qualitat terapèutica i el monitoratge de l’efecte d’aprenentatge constitueixen dues responsabilitats ineludibles durant l’adquisició i manteniment de noves modalitats terapèutiques. Les corbes CUSUM han estat utilitzades amb èxit per aquests dos propòsits. L’objectiu d’aquest estudi va ser avaluar la qualitat terapèutica i l’efecte d’aprenentatge a partir de les corbes CUSUM, associats a la introducció i desenvolupament de procediments endovasculars amb intenció de tractar en els territoris aorto-ilíac, fèmoro-popliti i renal, així com l’avaluació de l’eficàcia i seguretat dels procediments endovasculars diagnòstics i terapèutics realitzats a través d’un abordatge transhumeral. MATERIAL I MÈTODES: En primer lloc, pacients consecutius afectes d’arteriopatia obliterant aorto-ilíaca, fémoro-poplítia o renal amb indicació terapèutica endovascular, tractats per cirurgians vasculars a l’Hospital del Mar de Barcelona entre els anys 2003 i 2009, sobre els quals es varen registrar com a indicadors de qualitat la iatrogènia, la no consecució tècnica i el fracàs tècnic durant el primer mes. En segon lloc, pacients consecutius en els quals es van realitzar procediments endovasculars per punció humeral, tractats per cirurgians vasculars a l’Hospital del Mar entre els anys 2003 i 2010, sobre els quals es varen registrar com a indicadors de qualitat les complicacions aparegudes durant els procediments. Es van traslladar les dades a corbes CUSUM ajustades per la morbilitat mitja publicada per cada territori i pels abordatges humerals i les inflexions ascendents de les gràfiques varen ser avaluades posteriorment mitjançant subanàlisis per cada indicador de qualitat i proves Chi quadrat. RESULTATS: Durant el període 2003-2009 es van tractar 553 pacients, dels quals, 131 (23,7%) presentaven malaltia oclusiva aorto-ilíaca, 142 (25,7%) fémoro-poplítia i 128 (23,1%) renal. Es van practicar, respectivament, 3 PTA (angioplàstia transluminal percutània) simples i 117 PTA + stent; 8 PTA simples i 119 PTA + stent i 19 PTA simples i 109 PTA + stent. Els percentatges associats a iatrogènia varen ser 14,5%, 9,2% i 1,6%, de no consecució tècnica 6,9%, 10,6% i 1,6%, i de fracàs tècnic durant el primer mes 0,8%, 4,9% i 2,3%, respectivament. Les corbes CUSUM d’angioplàstia ilíaca varen mostrar dues inflexions ascendents a l’inici i al final del període, condicionades en ambdós casos per iatrogènia (p=0,034) i l’última, a més, per no consecució tècnica (p=0,033). Les corbes CUSUM d’angioplàstia fémoro-poplítia varen mostrar una inflexió ascendent progressiva en tot el període analitzat, atribuïble inicialment a iatrogènia i posteriorment a no consecució tècnica (p=0,05). Les corbes CUSUM d’angioplàstia renal no varen mostrar cap inflexió ascendent al llarg de tot el període. Pel que fa als procediments realitzats via transhumeral, tots excepte un cas van poder ser duts a terme d’acord amb la seva intenció inicial. La taxa global de complicacions va ser d’un 5,5% (5 pseudoaneurismes (2,1%), 4 accidents isquèmics transitoris (1,7%), 3 trombosis d’artèria humeral (1,3%) i 1 tamponament cardíac (0,4%)). En 4 d’aquests pacients va ser necessària una reparació quirúrgica oberta (30,8%). No es van observar diferències estadísticament significatives en relació a edat o sexe del pacient. Les corbes CUSUM creades per un risc teòric del 2% van mostrar 2 inflexions positives estadísticament significatives: una a la fase inicial de la sèrie associada a procediments diagnòstics (p=0,043) i una segona a la fase final de la sèrie associada a procediments terapèutics (p=0,018). CONCLUSIÓ: Les corbes CUSUM constitueixen un excel·lent sistema d’avaluació de la qualitat terapèutica que s’ofereix als nostres pacients en la introducció i desenvolupament de tècniques endovasculars. Els subanàlisis per a cada indicador de qualitat permeten identificar les causes atribuïbles a cada inflexió ascendentQuality of care and learning effect surveillance are two unavoidable responsibilities during acquirement and maintenance of new therapeutic techniques. CUSUM curves methodology have been successfully used for these two purposes. The aim of this study was to evaluate, applying CUSUM curves, the quality of care and the learning effect, associated with the introduction and development of intention to treat endovascular procedures in aorto-iliac, femoropopliteal and renal artery occlusive disease, as well as evaluating, the efficacy and safety of the endovascular diagnostic and therapeutic procedures performed through a brachial approach. MATERIAL AND METHODS: Firstly, consecutive patients with aorto-iliac, femoropopliteal or renal artery occlusive disease with endovascular therapeutic indication, treated by vascular surgeons in the Hospital del Mar of Barcelona between 2003 and 2009, of those were registered, as quality indicators, inability to cross the lesion, peri- and post-procedural complications and significant residual stenosis or occlusion at 1 month. Secondly, consecutive patients in which endovascular procedures through a brachial approach were performed, treated by vascular surgeons in the Hospital del Mar of Barcelona between 2003 and 2010, of those were registered, as quality indicators, all procedural complications. Data collected were transferred to adjusted CUSUM curves according to the average published morbidity given for each arterial territory and for brachial approach. Graphic ascending inflections were later evaluated with sub analysis for each quality indicator and Chi test. RESULTS: Between 2003-2009, 553 consecutive patients, scheduled for endovascular intervention of aorto-iliac (n = 131, 23.7%), femoropopliteal (n = 142, 25.7%) and renal artery (n = 128, 23.1%) occlusive disease were treated. 3 PTA (percutaneous transluminal angioplasty) and 117 PTA + stent; 8 PTA and 119 PTA + stent and 109 PTA + stent, were respectively performed. The percentages associated with peri- and post-procedural complications were 14.5%, 9.2% and 1.6%; failure to cross the lesion, 6.9%, 10.6% and 1.6%; and significant residual stenosis or occlusion at 1 month, 0.8%, 4.9% and 2.3%, respectively. Aorto-iliac CUSUM curve showed two upward inflections at the beginning and the end of the period, both associated with peri- and post-procedural complications (p = 0.034) and the last one also due to failure to cross the lesion (p = 0.033). Femoro-popliteal CUSUM curve moved progressively upward during all the period, initially related to peri- and post-procedural complications and later to failure to cross the lesion (p = 0.005). Renal CUSUM curve didn't show any upward inflection during the analysed period. When it comes to the procedures performed via brachial approach, all but one procedure were completed according to their scheduled intention. The overall complication rate was 5.5% (5 pseudoaneurysms (2.1%), 4 transient ischemic attack (1.7%), 3 brachial artery thromboses (1.3%) and 1 cardiac tamponade (0.4%). Surgical intervention was required in four of these patients (30.8%). No significant differences were observed according to age or sex. CUSUM curves created at a 2% theoretical risk showed two statistically significant upward inflections: one early in the series associated with diagnostic procedures (p=0.043) and another at the end of the study related to therapeutic interventions (p=0.018). CONCLUSION: CUSUM curves constitute an excellent tool for evaluating the quality of care provided to our patients during the introduction and development of endovascular techniques. Quality indicator sub analysis allows us to identify the causes attributable to every upward inflection of the curve

L'ús de la metodologia CUSUM pel control de qualitat i de l'efecte d'aprenentatge en els procediments endovasculars

El control de qualitat terapèutica i el monitoratge de l’efecte d’aprenentatge constitueixen dues responsabilitats ineludibles durant l’adquisició i manteniment de noves modalitats terapèutiques. L’objectiu d’aquest estudi va ser avaluar qualitat terapèutica i efecte d’aprenentatge a partir de corbes CUSUM, associats a la introducció i desenvolupament de procediments endovasculars incloent 553 pacients consecutius amb arteriopatia obliterant aorto-ilíaca, fémoro-poplítia o renal, tractats per cirurgians vasculars a l’Hospital del Mar entre 2003-2009, registrant-ne iatrogènia, no consecució tècnica i fracàs tècnic durant el primer mes i realitzant corbes CUSUM per a cada territori, que han acabat constituint un excel•lent sistema d’avaluació de qualitat terapèutica

L'ús de la metodologia CUSUM pel control de qualitat i de l'efecte d'aprenentatge en els procediments endovasculars

El control de qualitat terapèutica i el monitoratge de l'efecte d'aprenentatge constitueixen dues responsabilitats ineludibles durant l'adquisició i manteniment de noves modalitats terapèutiques. L'objectiu d'aquest estudi va ser avaluar qualitat terapèutica i efecte d'aprenentatge a partir de corbes CUSUM, associats a la introducció i desenvolupament de procediments endovasculars incloent 553 pacients consecutius amb arteriopatia obliterant aorto-ilíaca, fémoro-poplítia o renal, tractats per cirurgians vasculars a l'Hospital del Mar entre 2003-2009, registrant-ne iatrogènia, no consecució tècnica i fracàs tècnic durant el primer mes i realitzant corbes CUSUM per a cada territori, que han acabat constituint un excel·lent sistema d'avaluació de qualitat terapèutica

Genome-wide association meta-analysis identifies risk loci for abdominal aortic aneurysm and highlights PCSK9 as a therapeutic target

Abdominal aortic aneurysm (AAA) is a common disease with substantial heritability. In this study, we performed a genome-wide association meta-analysis from 14 discovery cohorts and uncovered 141 independent associations, including 97 previously unreported loci. A polygenic risk score derived from meta-analysis explained AAA risk beyond clinical risk factors. Genes at AAA risk loci indicate involvement of lipid metabolism, vascular development and remodeling, extracellular matrix dysregulation and inflammation as key mechanisms in AAA pathogenesis. These genes also indicate overlap between the development of AAA and other monogenic aortopathies, particularly via transforming growth factor β signaling. Motivated by the strong evidence for the role of lipid metabolism in AAA, we used Mendelian randomization to establish the central role of nonhigh-density lipoprotein cholesterol in AAA and identified the opportunity for repurposing of proprotein convertase, subtilisin/kexin-type 9 (PCSK9) inhibitors. This was supported by a study demonstrating that PCSK9 loss of function prevented the development of AAA in a preclinical mouse model. Genome-wide association meta-analysis of AAA identifies 121 independent risk loci and highlights potential therapeutic targets such as proprotein convertase, subtilisin/kexin-type 9 (PCSK9)

Genome-wide association meta-analysis identifies risk loci for abdominal aortic aneurysm and highlights PCSK9 as a therapeutic target

Abdominal aortic aneurysm (AAA) is a common disease with substantial heritability. In this study, we performed a genome-wide association meta-analysis from 14 discovery cohorts and uncovered 141 independent associations, including 97 previously unreported loci. A polygenic risk score derived from meta-analysis explained AAA risk beyond clinical risk factors. Genes at AAA risk loci indicate involvement of lipid metabolism, vascular development and remodeling, extracellular matrix dysregulation and inflammation as key mechanisms in AAA pathogenesis. These genes also indicate overlap between the development of AAA and other monogenic aortopathies, particularly via transforming growth factor β signaling. Motivated by the strong evidence for the role of lipid metabolism in AAA, we used Mendelian randomization to establish the central role of nonhigh-density lipoprotein cholesterol in AAA and identified the opportunity for repurposing of proprotein convertase, subtilisin/kexin-type 9 (PCSK9) inhibitors. This was supported by a study demonstrating that PCSK9 loss of function prevented the development of AAA in a preclinical mouse model

Genome-wide association meta-analysis identifies risk loci for abdominal aortic aneurysm and highlights PCSK9 as a therapeutic target.

Abdominal aortic aneurysm (AAA) is a common disease with substantial heritability. In this study, we performed a genome-wide association meta-analysis from 14 discovery cohorts and uncovered 141 independent associations, including 97 previously unreported loci. A polygenic risk score derived from meta-analysis explained AAA risk beyond clinical risk factors. Genes at AAA risk loci indicate involvement of lipid metabolism, vascular development and remodeling, extracellular matrix dysregulation and inflammation as key mechanisms in AAA pathogenesis. These genes also indicate overlap between the development of AAA and other monogenic aortopathies, particularly via transforming growth factor β signaling. Motivated by the strong evidence for the role of lipid metabolism in AAA, we used Mendelian randomization to establish the central role of nonhigh-density lipoprotein cholesterol in AAA and identified the opportunity for repurposing of proprotein convertase, subtilisin/kexin-type 9 (PCSK9) inhibitors. This was supported by a study demonstrating that PCSK9 loss of function prevented the development of AAA in a preclinical mouse model