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1.
Ann Surg Open ; 5(3): e464, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39310364

RESUMEN

Background: There is a paucity of data evaluating femoral arterial access training, despite significant morbidity/mortality associated with incorrect femoral arterial access. The aim of this study was to develop and evaluate a novel 2-component simulation-based curriculum to address a lack of standardized access training and identify the most frequent errors in access. Methods: The femoral arterial access curriculum was developed through a multi-disciplinary collaboration and utilized in-person simulation sessions in conjunction with online and in-person didactic training. Access errors and curriculum efficacy were assessed using mixed-methodology evaluation of video recordings of trainee arterial access pre- and postcurriculum. All recordings were reviewed and scored by 2 blinded, independent investigators. Results: Twenty-six participants completed the curriculum with pre- and postcurriculum recordings. Sixteen participants (62%) were in their first year of residency training. Fifteen participants (58%) belonged to general surgery residency, 9 (35%) to emergency medicine, 1 to vascular surgery, and 1 to interventional radiology residency programs. The global rating for the overall ability to obtain femoral arterial access under ultrasound guidance (0 = fail, 4 = excellent) improved following the curriculum (0.87 ± 0.15, 2.79 ± 1.26, P < 0.0001). Fourteen participants (54%) were unable to independently complete the procedure before training, compared to only 2 participants (8%) following the curriculum. Procedural completion time decreased from 7.14 ± 4.26 to 3.81 ± 2.53 minutes (P < 0.001). Most frequent errors, determined through qualitative analysis, included difficulty using the ultrasound and unsafe maneuvers. Conclusions: Before the curriculum, there were significant frequent errors in junior resident femoral arterial access with major patient safety concerns. A novel simulation-based femoral arterial access curriculum resulted in improved procedural skills across all metrics.

2.
J Surg Educ ; 81(10): 1473-1483, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39127532

RESUMEN

OBJECTIVE: Many surgical residencies have passed along attendings preferences and procedural knowledge as a highly utilized but informal resource. The objective was to assess the effect of providing operative steps and attending preferences on surgical resident performance. DESIGN: This was a prospective observational study with a survey-based design. SETTING: We created and shared vascular surgery operative steps including institutional and attending preferences with junior residents at the Massachusetts General Hospital. PARTICIPANTS: There were a total of 31 residents who completed a survey to assess self-perception of performance in operative knowledge and Accreditation Council for Graduate Medical Education (ACGME) Milestone criteria. RESULTS: Advice from colleagues was the most utilized resource, followed by web-based materials. Of the web-based materials, almost all residents utilized Google searches over other web-based resources designed to specifically help surgical trainees. The vascular surgery resource was used by 90% of residents more than 3 times per week to prepare for operative cases. There was significant improvement in patient positioning, instrument selection, operative field exposure, anatomy, sequence of procedure, procedure choices, and peri-operative care knowledge. CONCLUSIONS: Development of institutional resources that specifically capture attending surgeon procedural variations can improve resident performance, encourage resident autonomy, and provide a catalog of approaches to challenging operative situations.


Asunto(s)
Competencia Clínica , Internado y Residencia , Procedimientos Quirúrgicos Vasculares , Estudios Prospectivos , Procedimientos Quirúrgicos Vasculares/educación , Proyectos Piloto , Humanos , Educación de Postgrado en Medicina/métodos , Femenino , Masculino , Massachusetts , Adulto , Encuestas y Cuestionarios
3.
J Vasc Surg ; 80(4): 1269-1278.e2, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-38838967

RESUMEN

OBJECTIVE: Well-developed leadership skills have been associated with a better understanding of health care context, increased team performance, and improved patient outcomes. Surgeons, in particular, stand to benefit from leadership development. Although studies have focused on investigating knowledge gaps and needs of surgeons in leadership roles, there is a noticeable gap in the literature concerning leadership in vascular surgery. The goal of this study was to characterize current leadership attributes of vascular surgeons and understand demographic influences on leadership patterns. METHODS: This retrospective cohort study was a descriptive analysis of vascular surgeons and their observers who took the Leadership Practices Inventory (LPI) from 2020 to 2023. The LPI is a 30-question inventory that measures the frequency of specific leadership behaviors across five practices of leadership. RESULTS: A total of 110 vascular surgeons completed the LPI. The majority of participants were White (56%) and identified as male (60%). Vascular surgeons most frequently observed the "enabling others to act" leadership practice style (8.90 ± 0.74) by all evaluators. Vascular surgeons were most frequently above the 70th percentile in the "challenge the process" leadership practice style (49%) compared with the average of other leaders worldwide. Observers rated vascular surgeons as displaying significantly more frequent leadership behaviors than vascular surgeons rated themselves in every leadership practice style (P < .01). The only demographic variable associated with a significantly increased occurrence of achieving 70th percentile across all five leadership practice styles was the male gender: a multivariable model adjusting for objective experience showed that men were at least 3.5 times more likely to be rated above the 70th percentile than women. CONCLUSIONS: Vascular surgeons under-report the frequency at which they practice leadership skills across all five leadership practice styles and should recognize their strengths of enabling others to act and challenging the process. Men are recognized as exhibiting all five leadership practices more frequently than women, regardless of current position or experience level. This observation may reflect the limited leadership positions available for women, thereby restricting their opportunities to demonstrate leadership practices as frequently or recognizably as their male counterparts.


Asunto(s)
Equidad de Género , Liderazgo , Médicos Mujeres , Cirujanos , Procedimientos Quirúrgicos Vasculares , Humanos , Femenino , Masculino , Estudios Retrospectivos , Procedimientos Quirúrgicos Vasculares/normas , Procedimientos Quirúrgicos Vasculares/organización & administración , Cirujanos/organización & administración , Médicos Mujeres/estadística & datos numéricos , Factores Sexuales , Persona de Mediana Edad , Adulto , Actitud del Personal de Salud
4.
Ann Vasc Surg ; 106: 377-385, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38821470

RESUMEN

BACKGROUND: Series detailing complications after carotid endarterectomy (CEA) and transfemoral carotid stenting (tfCAS) for patients presenting with neurologic symptoms that are treated with systemic thrombolysis (ST) are sparse. We sought to determine if treatment with ST was associated with a higher rate of post-carotid intervention complications. METHODS: A multispecialty, institutional, prospectively maintained database was queried for symptomatic patients treated with CEA or tfCAS from 2007 to 2019. The primary outcomes of interest were bleeding complications (access/wound complications, hematuria, intracranial hemorrhage) or need for reintervention, stroke, and death. We compared rates of these outcomes between patients who were and were not treated with ST. To adjust for preoperative patient factors and confounding variables, propensity scores for assignment to ST and non-ST were calculated. RESULTS: There were 1,139 patients included (949 [82%] CEA and 190 [17%] tfCAS. All treated lesions were symptomatic (550 [48%] stroke, 603 [52%] transient ischemic attack). Fifty-six patients (5%) were treated with ST. Fifteen of 56 patients also underwent catheter-based intervention for stroke. ST was administered 0 to 1 day preoperatively in 21 (38%) patients, 2 to 6 days preoperatively in 27 (48%) patients, and greater than 6 days preoperatively in 8 (14%) patients. ST patients were more likely to present with stroke (93% vs. 45%; P < 0.001) and have higher preoperative Rankin scores. Unadjusted rate of bleeding/return to operating room was 3% for ST group and 3% for non-ST group (P = 0.60). Unadjusted rate of stroke was 4% for ST group and 3% for the non-ST group (P = 0.91), while perioperative mortality was 5% for ST group and 1% for non-ST group (P = 0.009). After adjusting for patient factors, preoperative antiplatelet/anticoagulation, and operative factors, ST was not associated with an increased odds of perioperative bleeding/return to the operating room (odds ratio 0.37; 95% confidence interval: 0.02-1.63; P = 0.309) or stroke (odds ratio 0.62; 95% confidence interval: 0.16-2.40; P = 0.493). CONCLUSIONS: ST does not convey a higher risk of complications after CEA or tfCAS. After controlling for other factors, patients that received ST had similar rates of local complications and stroke when compared to non-ST patients. Early carotid intervention is safe in patients that have received ST, and delays should be avoided in symptomatic patients given the high risk of recurrent stroke.


Asunto(s)
Bases de Datos Factuales , Endarterectomía Carotidea , Fibrinolíticos , Stents , Terapia Trombolítica , Humanos , Masculino , Femenino , Anciano , Endarterectomía Carotidea/efectos adversos , Endarterectomía Carotidea/mortalidad , Resultado del Tratamiento , Factores de Riesgo , Terapia Trombolítica/efectos adversos , Terapia Trombolítica/mortalidad , Factores de Tiempo , Estudios Retrospectivos , Medición de Riesgo , Persona de Mediana Edad , Fibrinolíticos/efectos adversos , Fibrinolíticos/administración & dosificación , Anciano de 80 o más Años , Accidente Cerebrovascular/etiología , Procedimientos Endovasculares/efectos adversos , Procedimientos Endovasculares/instrumentación , Procedimientos Endovasculares/mortalidad , Estenosis Carotídea/terapia , Estenosis Carotídea/diagnóstico por imagen , Estenosis Carotídea/mortalidad , Estenosis Carotídea/complicaciones , Ataque Isquémico Transitorio/etiología , Ataque Isquémico Transitorio/mortalidad
5.
Ann Surg ; 2024 May 21.
Artículo en Inglés | MEDLINE | ID: mdl-38771946

RESUMEN

OBJECTIVE: The objective of this study was to identify clinical and anatomic characteristics of Popliteal artery aneurysms (PAAs) associated with acutely limb threatening events. SUMMARY BACKGROUND DATA: Popliteal artery aneurysms (PAAs) are associated with high morbidity and mortality. Current guidelines recommend operative repair for PAAs with a diameter greater than 20 mm based on very limited evidence. METHODS: This retrospective cross-sectional cohort was derived from a multi-institutional database queried for all patients with a PAA from 2008 to 2022. Duplex ultrasound (DUS) characteristics of PAAs were abstracted by registered physicians in vascular interpretation. Symptom status at the time of DUS was divided into three categories: asymptomatic PAA, symptomatic PAA with claudication or chronic limb ischemia, and acutely limb threatening PAAs with a thromboembolic event, acute limb ischemia, or rupture. RESULTS: There were 470 PAAs identified in 331 patients. The mean age was 74 years at diagnosis, 94% of patients were white, and 97% of patients were male. In a univariate analysis, patient comorbidities and medications were not associated with symptom status. In a multivariate analysis including age, higher percent thrombus was significantly associated with symptomatic PAAs (RRR 15.2; CI 2.69-72.3; P<0.01) and PAAs with an acutely limb threatening event (RRR 17.9; CI 3.76-85.0; P<0.01). All other anatomic characteristics were not associated with symptom status. CONCLUSION: Percent thrombus was significantly associated with symptomatic PAAs and acutely limb threatening events, whereas diameter was not significantly associated with any symptom group. This analysis supports the use of percent thrombus in identifying high risk PAAs that warrant repair.

6.
Vasc Med ; 29(1): 58-63, 2024 02.
Artículo en Inglés | MEDLINE | ID: mdl-38131163

RESUMEN

INTRODUCTION: Duplex ultrasound (DUS) is the modality of choice for surveillance of popliteal artery aneurysms (PAAs). However, noninvasive vascular laboratories have no standard guidelines for reporting results. This study assessed reports of PAA DUS for inclusion of information pertinent to operative decision-making and timing of surveillance. METHODS: This study was a retrospective review of a multi-institutional repository that was queried for all patients with a PAA from 2008 to 2022 and confirmed via manual chart review. DUS reports were abstracted and images were individually annotated for features of interest including dimensions, flow abnormalities, and percent thrombus burden. RESULTS: A total of 166 PAAs in 130 patients had at least one DUS available for viewing. Postoperative surveillance of PAAs was performed at several intervals: the first at 30 months (IQR 3.7-113, n = 44), the second at 64 months (IQR 20-172, n = 31), and the third at 152 months (IQR 46-217, n = 16) after the operation. The largest diameter of operative PAAs (median 27.5 mm, IQR 21.8-38.0) was significantly greater than nonoperative PAAs (median 20.9 mm, IQR 16.7-27.3); p < 0.01. Fewer than 33 (21%) reports commented on patency of distal runoff. We calculated an average percent thrombus of 60% (IQR 19-81) in nonoperative PAAs, which is significantly smaller than 75% (IQR 58-89) in operative PAAs; p < 0.01. CONCLUSION: In this multi-institutional retrospective study, PAAs are often not followed at intervals recommended by the Society for Vascular Surgery guidelines and do not include all measurements necessary for clinical decision-making in the multi-institutional repository studied. There should be standardization of PAA DUS protocols performed by all noninvasive vascular laboratories to ensure completeness of PAA DUS images and inclusion of characteristics pertinent to clinical decision-making in radiology reports.


Asunto(s)
Aneurisma , Implantación de Prótesis Vascular , Aneurisma de la Arteria Poplítea , Trombosis , Humanos , Estudios Retrospectivos , Aneurisma/diagnóstico por imagen , Aneurisma/cirugía , Ultrasonografía , Trombosis/diagnóstico por imagen , Arteria Poplítea/diagnóstico por imagen , Arteria Poplítea/cirugía , Grado de Desobstrucción Vascular , Resultado del Tratamiento
7.
J Vasc Surg ; 78(5): 1180-1187, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37482141

RESUMEN

BACKGROUND: Although endovascular technology has resulted in a paradigm shift in treatment, medical management remains the standard of care for penetrating aortic ulcer (PAU) and intramural hematoma (IMH). This study aimed to detail the short- and long-term outcomes of symptomatic PAU/IMH. METHODS: Institutional data on symptomatic PAU/IMH were gathered (2005-2020). The primary outcome was the composite of recurrent symptoms, radiographic progression, intervention, rupture, and death from related or unknown cause. Factors associated with the primary outcome were determined using a Fine-Gray model with death from an unrelated cause as a competing risk. RESULTS: A total of 83 symptomatic patients treated with medical management aside from ruptures and type A dissections: 21 isolated PAU, 30 isolated IMH, and 32 IMH and PAU. Adverse outcomes included symptom recurrence in 14 (16.9%), radiographic progression to dissection or saccular aneurysm in 17 (20.5%), surgery in 20 (24.1%) (17 thoracic endovascular aortic repair, 1 endovascular aortic repair, 1 frozen elephant trunk, and 1 open repair), and rupture in 4 (4.8%). Twenty-seven patients (32.5%) died during follow-up: 6 from IMH treatment complications, 8 from an unknown cause, and 13 from other causes. The 30-day, 1-year, and 5-year cumulative incidences of the primary outcome was 26.5% (95% confidence interval [CI], 16.9%-37.0%), 44.9% (95% CI, 32.8%-56.2%), and 57.5% (95% CI, 42.4%-69.9%), respectively. IMH with PAU was associated with a significantly higher risk of the primary outcome compared with isolated IMH (subdistribution hazard ratio, 2.21; 95% CI, 1.09-4.50; P = .027) and isolated PAU (subdistribution hazard ratio, 3.58; 95% CI, 1.44-8.88; P = .006). CONCLUSIONS: Complications from symptomatic PAU and IMH are frequent, with intervention, recurrent symptoms, radiographic progression, rupture, or death affecting 25% of patients at 30 days after diagnosis and almost one-half of patients 1 year after diagnosis. Given the high rate of adverse events in this population, investigation into a more aggressive interventional strategy may warranted, especially in patients with a combined IMH and PAU.


Asunto(s)
Enfermedades de la Aorta , Úlcera Aterosclerótica Penetrante , Humanos , Enfermedades de la Aorta/diagnóstico por imagen , Enfermedades de la Aorta/cirugía , Aorta , Hematoma/diagnóstico por imagen , Hematoma/etiología , Hematoma/cirugía , Úlcera/diagnóstico por imagen , Úlcera/cirugía , Resultado del Tratamiento , Estudios Retrospectivos
8.
Ann Vasc Surg ; 97: 97-105, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37355013

RESUMEN

BACKGROUND: National guidelines stipulate that postoperative length-of-stay (LOS) after elective carotid endarterectomy (CEA) should not exceed 1 day on average, yet perioperative care coordination gaps may limit the ability for institutions to achieve this goal. Internal review determined that increased LOS after CEA at our institution was frequently attributable to urinary retention or postoperative hypertension. We designed and implemented a quality improvement (QI) protocol aiming to better our institutional performance in postoperative LOS after CEA, consisting of 2 Plan-Do-Study-Act (PDSA) cycles. METHODS: In the first PDSA cycle, a division-wide standardized protocol was developed by which antihypertensive medications were managed preoperatively and through postoperative day (POD) 1. This protocol included dedicated patient outreach with instructions for at-home antihypertensive management through the morning of POD 0. Second, alpha-1-blockade was administered to all male patients preoperatively. All patients receiving an elective CEA performed at our institution by vascular surgeons were included in the protocol. The primary outcome measure was defined percent failure of the LOS >1 day metric, with raw LOS as a secondary outcome measure. Process measures included adherence to the antihypertensive medication protocol and adherence to preoperative alpha-1 blockade. Balance measures included documented intraoperative hypotension and 30-day readmission. Fisher's exact test was used to evaluate relationships between preintervention and postintervention cohorts and the outcome measure. Wilcoxon rank-sum tests were used to evaluate relationships between cohorts and total LOS. RESULTS: Baseline performance on the LOS >1 day metric after elective CEA was 58.3% in the 8 months prior to intervention, across 48 patients. Both PDSA interventions were implemented simultaneously. In the 12 months after intervention, 64 patients met protocol inclusion criteria, including 19 symptomatic patients (29.7%). Process measure success for preoperative antihypertensive regimen adherence was 89.8%. For males not chronically prescribed alpha-1 blockade preoperatively, process measure success for adherence to preoperative alpha-1 blockade was 78.8%. The intraoperative hypotension balance measure occurred in 1 patient (1.6%). Performance on the LOS >1 day outcome measure was improved to 32.8% (P = 0.01). Performance on the raw LOS outcome measure was similar between the preintervention cohort (median 2 days, interquartile range [IQR] 1-2) and postintervention cohort (median 1 day, IQR 1-2, P = 0.07). Performance on the 30-day readmission balance measure was similar between preintervention (6.3%) and postintervention cohorts (9.4%, P = 0.73). CONCLUSIONS: The consensus-driven development and implementation of a QI protocol to reduce postoperative LOS after CEA showed promising results in our institution, with approximately 40% improvement in the primary outcome measure. Wider efforts to improve LOS after CEA should include a focus on minimization of postoperative hypertension and urinary retention.


Asunto(s)
Endarterectomía Carotidea , Hipertensión , Hipotensión , Retención Urinaria , Humanos , Masculino , Endarterectomía Carotidea/efectos adversos , Antihipertensivos/efectos adversos , Tiempo de Internación , Mejoramiento de la Calidad , Consenso , Estudios Retrospectivos , Resultado del Tratamiento , Hipertensión/diagnóstico , Hipertensión/tratamiento farmacológico
9.
Ann Vasc Surg ; 92: 9-17, 2023 May.
Artículo en Inglés | MEDLINE | ID: mdl-36682460

RESUMEN

BACKGROUND: Given the relative rarity of ruptured and symptomatic type I-III thoracoabdominal aortic aneurysms (TAAA), data is scarce with regard the outcomes of those who survive to repair. The goal of this study was to determine short and long-term outcomes after open repair of type I-III TAAA surgery for ruptured and symptomatic TAAA and compare the results to elective TAAA repairs. METHODS: All open type I-III TAAA repairs performed from 1987 to 2015 were evaluated using an institutional database. Charts were retrospectively evaluated for perioperative outcomes: major adverse event (MAE), in-hospital death, spinal cord ischemia (SCI) and long-term survival. Ruptured, symptomatic and elective repair cohorts were created for comparison. Univariate analysis was performed using the Fisher's exact test for categorical variables and analysis of variance (ANOVA) for continuous variables. Logistic regression was used for in-hospital endpoints; survival analysis was performed with Cox proportional hazards modelling and Kaplan-Meier techniques. RESULTS: Five hundred-sixteen patients had an open type I-III TAAA repair during the study period. Fifty-nine (11.4%) were performed for rupture and 51 (9.9%) were performed for symptomatic aneurysms (RAs). Ruptured and symptomatic groups were more likely to be older, female, and have larger presenting aortic diameters. Most of the ruptured and symptomatic cases were transferred from an outside facility (59.3% and 54.9%, respectively). Intraoperatively, the elective cohort was more likely to receive left heart bypass as an operative adjunct; ruptures were less likely to receive a renal bypass, and operative time was highest for the elective cohort. Perioperative mortality was 18.6% for ruptured, 2.0% for symptomatic, and 7.4% for elective indications. Ruptures were most likely to require new hemodialysis after repair (20.3% vs. 10.3% for elective, P = 0.02). On adjusted analysis, ruptures were more likely to suffer from perioperative death (adjusted odds ratio [AOR]: 4.5, 95% confidence interval (CI): 1.7-11.4) and MAEs (AOR: 2.8, 95% CI: 1.4-5.4). Ruptured and symptomatic aneurysms were not independently associated with SCI; however, preoperative hemodynamic instability was predictive (AOR: 8.7, 95% CI: 1.7-44.2). Both rupture and symptomatic cases were associated with decreased survival on Kaplan-Meier analysis with 5-year survival for ruptures at 35%, symptomatic at 47.7% and elective at 63.7%, P < 0.001. Adjusted hazards of death were 1.2 (95% CI: 0.9-1.8) in the symptomatic cohort and 2.3 (95% CI: 1.5-3.7) in the ruptured cohort. CONCLUSIONS: Open ruptured and symptomatic type I-III TAAA repairs can be performed with acceptable morbidity and mortality. Most symptomatic and rupture repairs were performed after transfer from another institution. Postoperative SCI is most strongly related to the preoperative hemodynamic status of the patient.


Asunto(s)
Aneurisma de la Aorta Torácica , Aneurisma de la Aorta Toracoabdominal , Implantación de Prótesis Vascular , Procedimientos Endovasculares , Humanos , Femenino , Factores de Riesgo , Aneurisma de la Aorta Torácica/diagnóstico por imagen , Aneurisma de la Aorta Torácica/cirugía , Centros de Atención Terciaria , Mortalidad Hospitalaria , Estudios Retrospectivos , Resultado del Tratamiento , Complicaciones Posoperatorias , Procedimientos Endovasculares/efectos adversos
10.
J Vasc Surg ; 77(1): 208-215.e3, 2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-36028157

RESUMEN

OBJECTIVE: Antiplatelet therapy has been a pillar of management for peripheral artery disease (PAD). However, a significant subset of patients with PAD will be resistant to certain antiplatelet medications and, therefore, have an increased risk of graft and/or stent thrombosis unknown to the surgeon. At present, no point-of-care testing to identity which patients will experience benefit from these medications has been incorporated into the treatment guidelines. Thromboelastography with platelet mapping affords an opportunity to evaluate real-time coagulation dynamics and platelet function. In the present prospective, observational study, we aimed to delineate the variation in response to antiplatelet therapy in patients with PAD undergoing revascularization. METHODS: All patients who were undergoing named vessel revascularization during December 2020 through April 2022 were prospectively enrolled. Platelet mapping assays were performed in three clinical phases: preoperative, postoperative inpatient, and postoperative outpatient. The distribution of platelet reactivity within patients receiving mono- vs dual antiplatelet therapy was assessed, and a between-group inferential analysis was performed. The effect of comorbidities and intervention subtype on platelet inhibition was also analyzed. RESULTS: A total of 521 platelet mapping samples from 143 individual patients were analyzed using thromboelastography with platelet mapping. We found wide variability in the distribution of platelet inhibition, with a range of 0 to 100 and an interquartile range of 37.6. Although platelet inhibition with clopidogrel 75 mg was higher on average (44.8 ± 30.2) than that with aspirin 81 mg (24.6 ± 23.7) or aspirin 325 mg (27.1 ± 26.4; P = .001), clopidogrel at 75 mg demonstrated the highest variability in response. CONCLUSIONS: These data have demonstrated significant variability in the response to both mono- and dual antiplatelet therapy in PAD patients undergoing lower extremity revascularization. Future research on the effect of this variability in response on the clinical outcomes could provide invaluable understanding of the perioperative thrombotic risk.


Asunto(s)
Enfermedad Arterial Periférica , Trombosis , Humanos , Inhibidores de Agregación Plaquetaria/efectos adversos , Clopidogrel/uso terapéutico , Estudios Prospectivos , Aspirina/efectos adversos , Enfermedad Arterial Periférica/diagnóstico , Enfermedad Arterial Periférica/tratamiento farmacológico , Enfermedad Arterial Periférica/cirugía , Trombosis/etiología , Trombosis/prevención & control , Quimioterapia Combinada , Resultado del Tratamiento
11.
Ann Vasc Surg ; 88: 42-50, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36058449

RESUMEN

BACKGROUND: Clinical outcomes in women with peripheral artery disease (PAD) after revascularization procedures are worse compared to men, yet there is little in the existing literature as why this may be the case. Platelet Mapping is an emerging point-of-care viscoelastic technology that measures the comprehensive properties of a blood clot, including fibrin-platelet interactions. This prospective observational study aimed to characterize the clinical and Platelet Mapping profiles of female and male patients undergoing lower extremity revascularization, and to correlate Platelet Mapping distribution to thrombotic potential. METHODS: All patients with a diagnosis of PAD undergoing named vessel open or endovascular revascularization to re-establish inflow, outflow, or both, during December 2020 and January 2022 were prospectively included. Patients were followed clinically for thrombosis for up to 1 year. Platelet Mapping assays were performed in 3 clinical phases: preoperative, postoperative inpatient, and postoperative outpatient. Inferential analysis between female and male patient was performed. The quartile distribution of Platelet Mapping metrics associated with thrombosis was used to infer to thrombotic potential. RESULTS: One hundred seven patients were enrolled, of which 37 (34.6%) were female. Female patients had significantly lower rates of uncontrolled diabetes (2.7% vs. 18.6%), hypertension requiring combination therapy (37.8% vs. 58.6%), chronic kidney disease (27.0% vs. 51.4%), coronary artery disease (29.7% vs. 57.1%), and myocardial infarction (16.2% vs. 35.7%) (all P < 0.05). Platelet reactivity was significantly higher in female patients with greater platelet aggregation (75.9 ± 23.3 vs. 63.5 ± 28.8) and lower platelet inhibition (23.8 ± 23.4 vs. 36.8 ± 28.9) (all P < 0.01). This trend was consistent over time when stratified by the postoperative inpatient and postoperative outpatient clinical phases. There was no statistically discernible difference in the use of antiplatelet therapy between groups, yet female patients continued to exhibit greater platelet reactivity when analyzed by the type of pharmacologic regimen (platelet aggregation on mono-antiplatelet therapy: 80.6 ± 21.0 in women versus 69.4 ± 25.0 in men; platelet aggregation on dual antiplatelet therapy: 67.9 ± 23.8 in women versus 44.8 ± 31.8 in men) (all P < 0.01). Twenty-one patients experienced postoperative graft/stent thrombosis within the study period. In relation to the overall study population, patients with thrombosis had Platelet Mapping metrics above the 50th percentile of overall platelet aggregation distribution. CONCLUSIONS: There is a growing appreciation for the differences in etiology, disease progression, and outcomes of cardiovascular conditions as they relate to sex. In this cohort, traditional cardiovascular risk factors were in lower prevalence in female patients. Platelet reactivity was found to be higher across clinical phases and antiplatelet regimens. High platelet reactivity was also associated with an increased incidence of thrombosis after lower extremity revascularization. These hypothesis-generating findings provide the basis for further exploration of sex-specific coagulation profiling in PAD patients.


Asunto(s)
Intervención Coronaria Percutánea , Enfermedad Arterial Periférica , Trombosis , Humanos , Femenino , Masculino , Inhibidores de Agregación Plaquetaria/efectos adversos , Caracteres Sexuales , Resultado del Tratamiento , Enfermedad Arterial Periférica/diagnóstico por imagen , Enfermedad Arterial Periférica/cirugía , Trombosis/etiología , Factores de Riesgo , Intervención Coronaria Percutánea/efectos adversos
12.
Diagnostics (Basel) ; 14(1)2023 Dec 25.
Artículo en Inglés | MEDLINE | ID: mdl-38201355

RESUMEN

DUS measurements for popliteal artery aneurysms (PAAs) specifically can be time-consuming, error-prone, and operator-dependent. To eliminate this subjectivity and provide efficient segmentation, we applied artificial intelligence (AI) to accurately delineate inner and outer lumen on DUS. DUS images were selected from a cohort of patients with PAAs from a multi-institutional platform. Encord is an easy-to-use, readily available online AI platform that was used to segment both the inner lumen and outer lumen of the PAA on DUS images. A model trained on 20 images and tested on 80 images had a mean Average Precision of 0.85 for the outer polygon and 0.23 for the inner polygon. The outer polygon had a higher recall score than precision score at 0.90 and 0.85, respectively. The inner polygon had a score of 0.25 for both precision and recall. The outer polygon false-negative rate was the lowest in images with the least amount of blur. This study demonstrates the feasibility of using the widely available Encord AI platform to identify standard features of PAAs that are critical for operative decision making.

13.
Ann Vasc Surg ; 87: 213-224, 2022 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-35339591

RESUMEN

BACKGROUND: Postoperative infection and wound dehiscence rates are higher than expected in peripheral artery disease and contribute significantly to limb loss and mortality. Microvascular pathology characterized by microthrombi and increased platelet aggregation have been cited as contributing factors to poor wound healing and infection. The emergence of viscoelastic assays, such as thromboelastography with platelet mapping (TEG-PM), have been utilized to identify prothrombotic states and may provide insight into a patient's microvascular coagulation profile. This prospective, observational study aimed to determine if TEG-PM could predict poor wound healing or infection following lower extremity revascularization. METHODS: All patients undergoing revascularization between December 2020 and January 2022 were prospectively included and followed for wound complications or non-surgical site infections of the index limb. TEG-PM metrics at the first postoperative follow-up in the nonevent group was compared to the TEG-PM sample preceding the diagnosis of infection/dehiscence in the event group. Cox proportional hazards (PH) regression was used to model the predictive value of viscoelastic parameters. Cut-point analysis to determine high-risk groups was determined by performing receiver operating characteristic curve analysis. RESULTS: Of the 102 patients, 18.6% experienced infection/dehiscence. The TEG-PM sample analyzed in the event group was, on average, 19.5 days prior to the diagnosis of an event. The event group had significantly higher maximum clot amplitude (MA) (47.3 mm ± 16.0 vs. 30.6 mm ± 15.3, P < 0.01), higher platelet aggregation (71.3% ± 27.7 vs. 31.2% ± 24.0, P < 0.01), and lower platelet inhibition (28.7% ± 27.7 vs. 68.7% ± 24.1, P < 0.01). Cox PH analysis identified platelet aggregation as an independent and consistent predictor of infection (hazard ratio = 1.04, 95% confidence interval 1.03-1.06, P < 0.01). An optimal cut-point of > 33.2 mm MA, > 46.6% platelet aggregation, or < 55.8% platelet inhibition identifies those with infection/dehiscence with 79.0-89.5% sensitivity. CONCLUSIONS: These are the first data to provide a quantitative link between prothrombotic viscoelastic coagulation profiles with the development of infection/dehiscence. Based on the cut-points of > 33.2 mm MA, > 46.6% platelet aggregation, or < 55.8% platelet inhibition, we recommend consideration of an enhanced antimicrobial or antithrombotic approach for these high risk groups.


Asunto(s)
Tromboelastografía , Trombosis , Humanos , Estudios Prospectivos , Resultado del Tratamiento , Pruebas de Función Plaquetaria , Cicatrización de Heridas
14.
Ann Vasc Surg ; 83: 20-25, 2022 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-35051586

RESUMEN

BACKGROUND: There is a paucity of data regarding the conversion rate from dry gangrene to wet gangrene after lower extremity revascularization. This study aimed to determine the rate of conversion from dry to wet gangrene within 30 days post-procedure in patients who underwent endovascular or open revascularization for critical limb ischemia. Secondary aims included determining the time to conversion and associated risk factors with conversion. METHODS: A multicenter, retrospective review was performed utilizing the MGH/Brigham Healthcare System's Research Patient Data Registry (RPDR). All adult patients who had lower extremity dry gangrene that underwent a revascularization procedure (endo, open, hybrid) from April 2002 to March 2020 were included. Patients who had no lower extremity gangrene, a concurrent amputation with the revascularization procedure, or wet gangrene on initial presentation were excluded. Univariate analysis was performed using the Fisher's exact test and Wilcoxon rank-sum test. RESULTS: There were 1,518 patients identified who underwent revascularization; 194 (12.8%) patients met inclusion criteria and served as our study cohort. There were 15 (7.7%) conversions from dry to wet gangrene within 30 days post-procedure. The mean time to conversion was 13.5 ± 8.6 days. Univariate analysis did not identify any associated risk factors for conversion. CONCLUSIONS: The rate of dry to wet gangrene conversion post revascularization is 7.7% within 30 days. The mean time of conversion is 13.5 ± 8.6 days.


Asunto(s)
Gangrena , Isquemia , Amputación Quirúrgica/efectos adversos , Gangrena/complicaciones , Humanos , Isquemia/diagnóstico por imagen , Isquemia/etiología , Isquemia/cirugía , Recuperación del Miembro/efectos adversos , Extremidad Inferior/irrigación sanguínea , Estudios Retrospectivos , Factores de Riesgo , Factores de Tiempo , Resultado del Tratamiento
15.
J Vasc Surg ; 75(3): 1091-1106, 2022 03.
Artículo en Inglés | MEDLINE | ID: mdl-34740806

RESUMEN

OBJECTIVE: Spinal cord ischemia (SCI) is one of the most devastating complications after descending thoracic aortic (DTA) and thoracoabdominal aortic (TAA) repairs. Patients who develop SCI have a poor prognosis, with mortality rates reaching 75% within the first year after surgery. Many factors have been shown to increase the risk of this complication, including the extent of TAA repair, length of aortic and collateral network coverage, embolization, and reduced spinal cord perfusion pressure. As a result, a variety of treatment strategies have been developed. We aimed to provide an up-to-date review of SCI rates with associated treatment algorithms from open and endovascular DTA and TAA repair. METHODS: Using PRISMA (preferred reporting items for systematic reviews and meta-analyses) guidelines, a literature review with the MeSH (medical subject headings) terms "spinal cord ischemia," "spinal cord ischemia prevention and mitigation strategies," "spinal cord ischemia rates," and "spinal cord infarction" was performed in the Cochrane and PubMed databases to find all peer-reviewed studies of DTA and TAA repair with SCI complications reported. The search was limited to 2012 to 2021 and English-language reports. MeSH subheadings, including diagnosis, complications, physiopathology, surgery, mortality, and therapy, were used to further restrict the included studies. Studies were excluded if they were not of humans, had not pertained to SCI after DTA or TAA operative repair, and if the study had primarily discussed neuromonitoring techniques. Additionally, studies with <40 patients or limited information regarding SCI protection strategies were excluded. Each study was individually reviewed by two of us (S.L. and A.D.) to assess the type and extent of aortic pathology, operative technique, SCI protection or mitigation strategies, rates of overall and permanent SCI symptoms, associations with SCI on multivariate analysis, and mortality. RESULTS: Of the 450 studies returned by the MeSH search strategy, 41 met the inclusion criteria and were included in the final analysis. For the endovascular DTA repair patients, the overall SCI rates ranged from 0% to 10.6%, with permanent SCI symptoms ranging from 0% to 5.1%. The rate of overall SCI after endovascular and open TAA repair was 0% to 35%. The permanent SCI symptom rate was reported by only one study of open repair at 1.1%. The permanent SCI symptom rate after endovascular TAA repair was 2% to 20.5%. CONCLUSIONS: The present review has provided an up-to-date review of the current rates of SCI and the prevention and mitigation strategies used during DTA and TAA repair. We found that a multimodal approach, including a bundled institutional protocol, staging of multiple repairs, preservation of the collateral blood flow network, augmented spinal cord perfusion, selective cerebrospinal fluid drainage, and distal aortic perfusion during open TAA repairs, appears to be important in reducing the risk of SCI.


Asunto(s)
Aorta Torácica/cirugía , Enfermedades de la Aorta/cirugía , Implantación de Prótesis Vascular/efectos adversos , Procedimientos Endovasculares/efectos adversos , Isquemia de la Médula Espinal/prevención & control , Algoritmos , Aorta Torácica/fisiopatología , Enfermedades de la Aorta/mortalidad , Enfermedades de la Aorta/fisiopatología , Implantación de Prótesis Vascular/mortalidad , Técnicas de Apoyo para la Decisión , Procedimientos Endovasculares/mortalidad , Humanos , Medición de Riesgo , Factores de Riesgo , Isquemia de la Médula Espinal/etiología , Isquemia de la Médula Espinal/mortalidad , Isquemia de la Médula Espinal/fisiopatología , Factores de Tiempo , Resultado del Tratamiento
16.
J Vasc Surg ; 75(3): 1107-1115, 2022 03.
Artículo en Inglés | MEDLINE | ID: mdl-34788649

RESUMEN

OBJECTIVE: Thromboelastography (TEG) is diagnostic modality that analyzes real-time blood coagulation parameters. Clinically, TEG primarily allows for directed blood component resuscitation among patients with acute blood loss and coagulopathy. The utilization of TEG has been widely adopted in among other surgical specialties; however, its use in vascular surgery is less prominent. We aimed to provide an up-to-date review of TEG utilization in vascular and endovascular surgery. METHODS: Using Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines, a literature review with the Medical Subject Headings (MeSH) terms "TEG and arterial events", "TEG and vascular surgery", "TEG and vascular", "TEG and endovascular surgery", "TEG and endovascular", "TEG and peripheral artery disease", "TEG and prediction of arterial events", "TEG and prediction of complications ", "TEG and prediction of thrombosis", "TEG and prediction of amputation", and "TEG and amputation" was performed in Cochrane and PubMed databases to identify all peer-reviewed studies of TEG utilization in vascular surgery, written between 2000 and 2021 in the English language. The free-text and MeSH subheadings search terms included diagnosis, complications, physiopathology, surgery, mortality, and therapy to further restrict the articles. Studies were excluded if they were not in humans or pertaining to vascular or endovascular surgery. Additionally, case reports and studies with limited information regarding TEG utilization were excluded. Each study was independently reviewed by two researchers to assess for eligibility. RESULTS: Of the 262 studies identified through the MeSH strategy, 15 studies met inclusion criteria and were reviewed and summarized. Literature on TEG utilization in vascular surgery spanned cerebrovascular disease (n = 3), peripheral arterial disease (n = 3), arteriovenous malformations (n = 1), venous thromboembolic events (n = 7), and perioperative bleeding and transfusion (n = 1). In cerebrovascular disease, TEG may predict the presence and stability of carotid plaques, analyze platelet function before carotid stenting, and compare efficacy of antiplatelet therapy after stent deployment. In peripheral arterial disease, TEG has been used to predict disease severity and analyze the impact of contrast on coagulation parameters. In venous disease, TEG may predict hypercoagulability and thromboembolic events among various patient populations. Finally, TEG can be utilized in the postoperative setting to predict hemorrhage and transfusion requirements. CONCLUSIONS: This systematic review provides an up-to-date summarization of TEG utilization in multiple facets of vascular and endovascular surgery.


Asunto(s)
Coagulación Sanguínea , Procedimientos Endovasculares , Monitoreo Intraoperatorio , Tromboelastografía , Enfermedades Vasculares/cirugía , Procedimientos Quirúrgicos Vasculares , Pérdida de Sangre Quirúrgica , Transfusión Sanguínea , Procedimientos Endovasculares/efectos adversos , Humanos , Hemorragia Posoperatoria/sangre , Hemorragia Posoperatoria/diagnóstico , Hemorragia Posoperatoria/terapia , Valor Predictivo de las Pruebas , Resultado del Tratamiento , Enfermedades Vasculares/sangre , Enfermedades Vasculares/diagnóstico , Procedimientos Quirúrgicos Vasculares/efectos adversos
17.
J Vasc Surg ; 74(4): 1109-1116, 2021 10.
Artículo en Inglés | MEDLINE | ID: mdl-33887425

RESUMEN

OBJECTIVE: Splenectomy is often performed during open thoracoabdominal aortic aneurysm (TAAA) repair, because capsular tears are common and can be associated with significant bleeding. It is unknown whether splenectomy affects the short- or long-term outcomes after TAAA repair. METHODS: All open type I to IV TAAA repairs performed from 1987 to June 2015 were evaluated using a single institutional database. The primary endpoints were in-hospital death, major adverse events (MAE) and long-term survival. The secondary endpoint was hospital length of stay (LOS). All repairs performed for aneurysm rupture were excluded. Univariate analysis was conducted using the Fisher's exact test for categorical variables and the Wilcoxon rank sum test for continuous variables. Logistic and linear multivariable regression were used for the in-hospital endpoints, and survival analyses were performed using Cox proportional hazards modeling and Kaplan-Meier techniques. RESULTS: A total of 649 patients met the study inclusion criteria. Of the 649 patients, 150 (23%) underwent concurrent splenectomy (CS) and six required emergency splenectomy secondary to bleeding postoperatively, leading to 156 cases of total in-hospital splenectomy. The perioperative mortality rate was 5.2% in the CS group and 5.2% in the non-CS group (P = 1.0). MAE were experienced by 48% of the CS patients compared with 34% of the non-CS patients (P = .003). Multivariable analysis revealed splenectomy was not independently predictive of perioperative death (adjusted odds ratio, 0.95; 95% confidence interval [CI], 0.41-2.23; P = .9). However, splenectomy was independently associated with any MAE (adjusted odds ratio, 1.78; 95% CI, 1.19-2.65; P = .005). Splenectomy was also associated with a longer length of stay (+5.39 days; 95% CI, 1.86-8.92; P = .003). No survival difference was found between the cohorts in the total splenectomy cohort in the unadjusted (log-rank P = 1.0) or adjusted (splenectomy adjusted hazard ratio, 1.02; 95% confidence interval, 0.78-1.35; P = .9). CONCLUSIONS: CS during open TAAA repair did not lead to increased perioperative mortality but did lead to significantly increased perioperative morbidity and longer hospital lengths of stay. We found no difference in long-term survival outcomes when CS was performed. Splenectomy during TAAA repair did not affect long-term survival.


Asunto(s)
Aneurisma de la Aorta Torácica/cirugía , Implantación de Prótesis Vascular , Procedimientos Endovasculares , Esplenectomía , Anciano , Aneurisma de la Aorta Torácica/diagnóstico , Aneurisma de la Aorta Torácica/mortalidad , Implantación de Prótesis Vascular/efectos adversos , Implantación de Prótesis Vascular/mortalidad , Boston , Bases de Datos Factuales , Procedimientos Endovasculares/efectos adversos , Procedimientos Endovasculares/mortalidad , Femenino , Mortalidad Hospitalaria , Hospitales de Alto Volumen , Humanos , Tiempo de Internación , Masculino , Complicaciones Posoperatorias/etiología , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Esplenectomía/efectos adversos , Esplenectomía/mortalidad , Factores de Tiempo , Resultado del Tratamiento
18.
J Heart Lung Transplant ; 37(5): 604-610, 2018 05.
Artículo en Inglés | MEDLINE | ID: mdl-29482932

RESUMEN

BACKGROUND: Recipient-related factors, such as education level and type of health insurance, are known to affect heart transplantation outcomes. Pre-operative employment status has shown an association with survival in abdominal organ transplant patients. We sought to evaluate the effect of work status of heart transplant (HTx) recipients at the time of listing and at the time of transplantation on short- and long-term survival. METHODS: We evaluated the United Network for Organ Sharing (UNOS) registry for all adult HTx recipients from 2001 to 2014. Recipients were grouped based on their work status at listing and at heart transplantation. Kaplan-Meier estimates illustrated 30-day, 1-year, 5-year, and 10-year survival comparing working with non-working groups. The Cox proportional hazards regression model was applied to adjust for covariates that could potentially confound the post-transplantation survival analysis. RESULTS: Working at listing for HTx was not significantly associated with 30-day and 1-year survival. However, 5- and 10-year mortality were 14.5% working vs 19.8% not working (p < 0.0001) and 16% working vs 26% not working (p < 0.0001), respectively. Working at HTx appeared to be associated with a survival benefit at every time interval, with a trend toward improved survival at 30 days and 1 year and a significant association at 5 and 10 years. Kaplan-Meier analysis demonstrated a 5% and 10% decrease in 5- and 10-year mortality, respectively, for the working group compared with the group not working at transplantation. The Cox proportional hazards regression model showed that working at listing and working at transplantation were each associated with decreased mortality (hazard ratio [HR] = 0.8, 95% confidence interval [CI] 0.71 to 0.91; and HR = 0.76, 95% CI 0.65 to 0.89, respectively). CONCLUSIONS: This study is the first analysis of UNOS STAR data on recipient work status pre-HTx demonstrating: (1) an improvement in post-transplant survival for working HTx candidates; and (2) an association between working pre-HTx and longer post-HTx survival. Given that work status before HTx may be a modifiable risk factor for better outcomes after HTx, we strongly recommend that UNOS consider these important findings for moving forward this patient-centered research on work status. Working at listing and working at HTx are associated with long-term survival benefits. The association may be reciprocal, where working identifies less ill patients and also improves well-being. Consideration should be given to giving additional weight to work status during organ allocation. Work status may also be a modifiable factor associated with better post-HTx outcomes.


Asunto(s)
Empleo , Insuficiencia Cardíaca/mortalidad , Insuficiencia Cardíaca/cirugía , Trasplante de Corazón , Adolescente , Adulto , Anciano , Niño , Preescolar , Bases de Datos Factuales , Femenino , Trasplante de Corazón/mortalidad , Humanos , Masculino , Persona de Mediana Edad , Periodo Preoperatorio , Estudios Retrospectivos , Tasa de Supervivencia , Factores de Tiempo , Resultado del Tratamiento , Adulto Joven
19.
Neurobiol Learn Mem ; 124: 34-47, 2015 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-26182988

RESUMEN

The use of viral vector technology to deliver short hairpin RNAs (shRNAs) to cells of the nervous system of many model organisms has been widely utilized by neuroscientists to study the influence of genes on behavior. However, there have been numerous reports that delivering shRNAs to the nervous system can lead to neurotoxicity. Here we report the results of a series of experiments where adeno-associated viruses (AAV), that were engineered to express shRNAs designed to target known plasticity associated genes (i.e. Arc, Egr1 and GluN2A) or control shRNAs that were designed not to target any rat gene product for depletion, were delivered to the rat basal and lateral nuclei of the amygdala (BLA), and auditory Pavlovian fear conditioning was examined. In our first set of experiments we found that animals that received AAV (3.16E13-1E13 GC/mL; 1 µl/side), designed to knockdown Arc (shArc), or control shRNAs targeting either luciferase (shLuc), or nothing (shCntrl), exhibited impaired fear conditioning compared to animals that received viruses that did not express shRNAs. Notably, animals that received shArc did not exhibit differences in fear conditioning compared to animals that received control shRNAs despite gene knockdown of Arc. Viruses designed to harbor shRNAs did not induce obvious morphological changes to the cells/tissue of the BLA at any dose of virus tested, but at the highest dose of shRNA virus examined (3.16E13 GC/mL; 1 µl/side), a significant increase in microglia activation occurred as measured by an increase in IBA1 immunoreactivity. In our final set of experiments we infused viruses into the BLA at a titer of (1.60E+12 GC/mL; 1 µl/side), designed to express shArc, shLuc, shCntrl or shRNAs designed to target Egr1 (shEgr1), or GluN2A (shGluN2A), or no shRNA, and found that all groups exhibited impaired fear conditioning compared to the group which received a virus that did not express an shRNA. The shEgr1 and shGluN2A groups exhibited gene knockdown of Egr1 and GluN2A compared to the other groups examined respectively, but Arc was not knocked down in the shArc group under these conditions. Differences in fear conditioning among the shLuc, shCntrl, shArc and shEgr1 groups were not detected under these circumstances; however, the shGluN2A group exhibited significantly impaired fear conditioning compared to most of the groups, indicating that gene specific deficits in fear conditioning could be observed utilizing viral mediated delivery of shRNA. Collectively, these data indicate that viral mediated shRNA expression was toxic to neurons in vivo, under all viral titers examined and this toxicity in some cases may be masking gene specific changes in learning. Therefore, the use of this technology in behavioral neuroscience warrants a heightened level of careful consideration and potential methods to alleviate shRNA induced toxicity are discussed.


Asunto(s)
Amígdala del Cerebelo/virología , Condicionamiento Clásico/fisiología , Dependovirus/fisiología , Miedo/fisiología , Vectores Genéticos/administración & dosificación , Neuronas/virología , ARN Interferente Pequeño/toxicidad , Amígdala del Cerebelo/fisiología , Animales , Proteínas del Citoesqueleto/metabolismo , Proteína 1 de la Respuesta de Crecimiento Precoz/metabolismo , Técnicas de Silenciamiento del Gen , Masculino , Proteínas del Tejido Nervioso/metabolismo , Neuronas/fisiología , Subunidades de Proteína/metabolismo , Ratas , Ratas Sprague-Dawley
20.
Mol Brain ; 8: 12, 2015 Feb 24.
Artículo en Inglés | MEDLINE | ID: mdl-25887710

RESUMEN

BACKGROUND: Viral vectors are frequently used to deliver and direct expression of transgenes in a spatially and temporally restricted manner within the nervous system of numerous model organisms. Despite the common use of viral vectors to direct ectopic expression of transgenes within the nervous system, creating high titer viral vectors that are capable of expressing very large transgenes or difficult to express transgenes imposes unique challenges. Here we describe the development of adeno-associated viruses (AAV) and lentiviruses designed to express the large and difficult to express GluN2A or GluN2B subunits of the N-methyl-D-aspartate receptor (NMDA) receptor, specifically within neurons. RESULTS: We created a number of custom designed AAV and lentiviral vectors that were optimized for large transgenes, by minimizing DNA sequences that were not essential, utilizing short promoter sequences of 8 widely used promoters (RSV, EFS, TRE3G, 0.4αCaMKII, 1.3αCaMKII, 0.5Synapsin, 1.1Synapsin and CMV) and utilizing a very short (~75 bps) 3' untranslated sequence. Not surprisingly these promoters differed in their ability to express the GluN2 subunits, however surprisingly we found that the neuron specific synapsin and αCaMKII, promoters were incapable of conferring detectable expression of full length GluN2 subunits and detectable expression could only be achieved from these promoters if the transgene included an intron or if the GluN2 subunit transgenes were truncated to only include the coding regions of the GluN2 transmembrane domains. CONCLUSIONS: We determined that viral packaging limit, transgene promoter and the presence of an intron within the transgene were all important factors that contributed to being able to successfully develop viral vectors designed to deliver and express GluN2 transgenes in a neuron specific manner. Because these vectors have been optimized to accommodate large open reading frames and in some cases contain an intron to facilitate expression of difficult to express transgenes, these viral vectors likely could be useful for delivering and expressing many large or difficult to express transgenes in a neuron specific manner.


Asunto(s)
Vectores Genéticos/metabolismo , Lentivirus/metabolismo , Neuronas/metabolismo , Transgenes , Animales , Dependovirus/metabolismo , Genoma Viral , Proteínas Fluorescentes Verdes/metabolismo , Intrones/genética , Masculino , Ratones Endogámicos C57BL , Proteínas Mutantes/metabolismo , Plásmidos/metabolismo , Regiones Promotoras Genéticas , Ratas Sprague-Dawley , Receptores de N-Metil-D-Aspartato/metabolismo , Virus del Sarcoma de Rous/metabolismo
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