RESUMEN
BACKGROUND: Male gender is a well-established risk factor for abdominal aortic aneurysm (AAA), whereas estrogen is hypothesized to play a protective role. Although rupture rates are higher in women, these reasons remain unknown. In the present study, we sought to determine if female mice are protected from AAA rupture. MATERIALS AND METHODS: Apolipoprotein E-deficient male and female mice (aged 7 wk; n = 25 per group) were infused with angiotensin II (AngII; 2000 ng/kg/min) plus ß-aminopropionitrile (BAPN) in the drinking water for 28 d to test the effects of gender on AAA rupture. Separately, a second group of male apolipoprotein E-deficient mice underwent AngII infusion + BAPN while being fed high-fat phytoestrogen free or a high-fat phytoestrogen diet to assess effects of phytoestrogens on rupture. In a third group, female mice either underwent oophorectomy or sham operation 4 wk before infusion of AngII and BAPN to further test the effects of female hormones on AA rupture. Surviving mice abdominal aorta were collected for histology, cytokine array, and gelatin zymography on postoperative day 28. RESULTS: Female mice had decreased AAA rupture rates (16% versus 46%; P = 0.029). Female mice expressed fewer elastin breaks (P = 0.0079) and decreased smooth muscle cell degradation (P = 0.0057). Multiple cytokines were also decreased in the female group. Gelatin zymography demonstrated significantly decreased pro-matrix metalloproteinase 2 in female mice (P = 0.001). Male mice fed a high dose phytoestrogen diet failed to decrease AAA rupture. Female mice undergoing oophorectomy did not have accelerated aortic rupture. CONCLUSIONS: These data are the first to attempt to tease out hormonal effects on AAA rupture and the possible role of gender in rupture.
Asunto(s)
Aorta Abdominal/patología , Aneurisma de la Aorta Abdominal/complicaciones , Rotura de la Aorta/epidemiología , Administración Oral , Aminopropionitrilo/administración & dosificación , Aminopropionitrilo/toxicidad , Angiotensina II/administración & dosificación , Angiotensina II/toxicidad , Animales , Aneurisma de la Aorta Abdominal/inducido químicamente , Rotura de la Aorta/etiología , Modelos Animales de Enfermedad , Femenino , Humanos , Masculino , Ratones , Ratones Noqueados para ApoE , Factores Protectores , Factores SexualesRESUMEN
OBJECTIVE: Few large-animal models exist for the study of aortic aneurysms. ß-Aminopropionitrile (BAPN) is a compound known to cause aortic aneurysms by inhibiting lysyl oxidase, a collagen cross-linking enzyme. It is hypothesized that BAPN plus aneurysm induction surgery would result in significant aneurysm formation in swine with biologic properties similar to human disease. METHODS: Initial experiments were performed in uncastrated male swine not treated with BAPN (surgery alone). Subsequently, uncastrated male swine were fed BAPN (0.15 g/kg) for 7 days before undergoing surgery; the infrarenal aorta was circumferentially dissected and measured, balloon dilated, and perfused with elastase (500 units) and type I collagenase (8000 units), with extraluminal elastase application. In the BAPN groups, daily BAPN feedings continued until swine harvest at postoperative days 7, 14, and 28. RESULTS: Swine undergoing surgery alone (n = 12) had significantly less dilation at 28 days compared with BAPN + surgery swine (51.9% ± 29.2% [0%-100%] vs 113.5% ± 30.2% [52.9%-146.2%]; P < .0003). Mean aortic dilation in animals undergoing treatment with surgery and BAPN was 86.9% ± 47.4% (range, 55.6%-157.1%), 105.4% ± 58.1% (50%-133.3%), and 113.5% ± 30.2% (52.9%-146.2%) at 7, 14, and 28 days, respectively. In the BAPN + surgery group, significant elastolysis was present at all time points, whereas aortic wall collagen content was not significantly different. Smooth muscle cells were significantly depleted at 14 and 28 days, and M1 macrophages were increased at 14 and 28 days (P < .05, all). Matrix metalloproteinase 2 was elevated at 7 days (P < .05). Multiple proinflammatory cytokines were elevated within the aortic wall of BAPN + surgery swine. CONCLUSIONS: BAPN plus surgery resulted in significantly larger aortic aneurysms than surgery alone and was critical to aneurysm formation in this novel swine model. Hallmarks of human disease, such as elastin fragmentation, smooth muscle cell depletion, macrophage infiltration, matrix metalloproteinase activation, and proinflammatory cytokine expression, were observed in BAPN-treated swine. This model better parallels many of the characteristics of human AAAs and may be suitable for prehuman drug trials.
Asunto(s)
Aminopropionitrilo , Angioplastia de Balón , Aorta Abdominal , Aneurisma de la Aorta Abdominal/inducido químicamente , Colagenasas , Elastasa Pancreática , Animales , Aorta Abdominal/metabolismo , Aorta Abdominal/patología , Aneurisma de la Aorta Abdominal/metabolismo , Aneurisma de la Aorta Abdominal/patología , Citocinas/metabolismo , Dilatación Patológica , Modelos Animales de Enfermedad , Progresión de la Enfermedad , Mediadores de Inflamación/metabolismo , Macrófagos/metabolismo , Macrófagos/patología , Masculino , Metaloproteinasa 2 de la Matriz/metabolismo , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/patología , Miocitos del Músculo Liso/metabolismo , Miocitos del Músculo Liso/patología , Sus scrofa , Factores de Tiempo , Remodelación VascularRESUMEN
OBJECTIVE: Major adverse limb events (MALEs) and major adverse cardiovascular events (MACEs) at 30 days provide standardized metrics for comparison and have been adopted by the Society for Vascular Surgery's objective performance goals for critical limb ischemia. However, MALEs and MACEs have not been widely adopted within the claudication population, and the comparative outcomes after lower extremity bypass (LEB) and infrainguinal endovascular intervention (IEI) remain unclear. The purpose of this study was to compare MALEs and MACEs after LEB and IEI in a contemporary national cohort and to determine predictors of MALEs and MACEs after revascularization for claudication. METHODS: A national data set of LEB and IEI performed for claudication was obtained using National Surgical Quality Improvement Program vascular targeted Participant Use Data Files from 2011 to 2014. Patients were stratified by LEB vs IEI and compared by appropriate univariate analysis. The primary outcomes were MALE (defined as untreated loss of patency, reintervention on the index arterial segment, or amputation of the index limb) and MACE (defined as stroke, myocardial infarction, or death). Multivariable logistic regression was used to identify predictors of MALEs and MACEs. RESULTS: A total of 3925 infrainguinal revascularization procedures (2155 LEB and 1770 IEI) were performed for claudication. There was no difference in 30-day MALEs between LEB and IEI (4.0% vs 3.2%; P = .17). On multivariable logistic regression, predictors of 30-day MALEs included tibial revascularization (odds ratio [OR], 2.2; P < .0001) and prior LEB on the same arterial segment (OR, 1.8; P = .004). LEB had significantly higher 30-day MACEs (2.0% vs 1.0%; P = .01) but similar mortality (0.5% vs 0.4%; P = .6). Predictors of MACEs included LEB vs IEI (OR, 2.1; P = .01), chronic obstructive pulmonary disease (OR, 2.2; P = .01), dialysis dependence (OR, 4.4; P = .003), and diabetes (OR, 1.9; P = .02). CONCLUSIONS: In this large national cohort, LEB and IEI for claudication are associated with similar 30-day MALEs. Tibial revascularization and revascularization after prior failed bypass predict MALEs in claudicants and should therefore be undertaken with caution. LEB was associated with more 30-day MACEs but comparable 30-day mortality compared with IEI. Patients with end-stage renal disease, chronic obstructive pulmonary disease, and diabetes are at high risk for MACEs. The risk of 30-day MACEs after LEB should be weighed against the longer term outcomes of LEB vs IEI and conservative management, particularly in these higher risk patients. This analysis helps define contemporary 30-day outcomes after infrainguinal revascularization performed for claudication and serves as a baseline with which the short-term outcomes of future treatments can be compared.
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Procedimientos Endovasculares/efectos adversos , Claudicación Intermitente/cirugía , Extremidad Inferior/irrigación sanguínea , Infarto del Miocardio/epidemiología , Enfermedad Arterial Periférica/cirugía , Accidente Cerebrovascular/epidemiología , Injerto Vascular/efectos adversos , Anciano , Comorbilidad , Bases de Datos Factuales , Procedimientos Endovasculares/mortalidad , Femenino , Humanos , Incidencia , Claudicación Intermitente/diagnóstico por imagen , Claudicación Intermitente/mortalidad , Claudicación Intermitente/fisiopatología , Recuperación del Miembro , Masculino , Persona de Mediana Edad , Infarto del Miocardio/diagnóstico , Infarto del Miocardio/mortalidad , Enfermedad Arterial Periférica/diagnóstico por imagen , Enfermedad Arterial Periférica/mortalidad , Enfermedad Arterial Periférica/fisiopatología , Estudios Retrospectivos , Factores de Riesgo , Accidente Cerebrovascular/diagnóstico , Accidente Cerebrovascular/mortalidad , Factores de Tiempo , Resultado del Tratamiento , Estados Unidos/epidemiología , Injerto Vascular/mortalidadRESUMEN
OBJECTIVE: Resolvins have been shown to attenuate inflammation, whereas NETosis, the process of neutrophils releasing neutrophil extracellular traps (NETs), produces increased inflammation. It is hypothesized that treatment of animals with resolvin D1 (RvD1) would reduce abdominal aortic aneurysm (AAA) formation by inhibiting NETosis. METHODS: Wild-type 8- to 12-week-old C57BL/6 male mice (n = 47) and apolipoprotein E-deficient (ApoE-/-) mice (n = 20) were used in two models to demonstrate the effects of RvD1 on AAA growth. In the topical elastase AAA model, wild-type mice were divided into three groups: a deactivated elastase control group, in which sham surgery was performed using deactivated elastase and mice were intravenously injected with phosphate-buffered saline (PBS) once a day until harvest; an elastase group, in which active elastase was used to induce AAA and mice were injected with PBS daily until harvest; and an RvD1-treated group, in which AAA was induced and mice were injected with RvD1 daily until harvest. In the angiotensin II (Ang II)-induced AAA model, ApoE-/- mice were fed a high-fat diet and implanted with osmotic infusion pumps containing Ang II (1000 ng/kg/min). The Ang II model was divided into two groups: an Ang II control group, in which Ang II was delivered and mice were injected with PBS daily until harvest; and an RvD1-treated group, in which Ang II was delivered and mice were injected with RvD1 daily until harvest. On postoperative day 3, day 14, or day 28, aortic and blood samples were collected for Western blot, histology, cytokine array, enzyme-linked immunosorbent assay, and gelatin zymography after aortic diameter measurement. RESULTS: The day 14 RvD1-treated group demonstrated 42% reduced AAA diameter compared with the elastase group (P < .001). On postoperative day 3, the RvD1-treated group showed decreased levels of NETosis markers citrullinated histone H3 (P = .04) and neutrophil elastase (P = .002) compared with the elastase group. Among important cytokines involved in AAA formation, interleukin (IL) 1ß was downregulated (P = .02) whereas IL-10, a protective cytokine, was upregulated (P = .01) in the RvD1-treated group. Active matrix metalloproteinase 2 also decreased in the RvD1-treated group (P = .03). The RvD1-treated group in the Ang II AAA model, a second model, demonstrated reduced AAA diameter compared with the Ang II control group on day 28 (P < .046). The RvD1-treated group showed decreased levels of citrullinated histone H3 on day 3 (P = .002). Cytokines interferon γ, IL-1ß, C-X-C motif chemokine ligand 10, monocyte chemotactic protein 1, and regulated on activation, normal T cell expressed and secreted (RANTES) were all decreased on day 28 (P < .05). CONCLUSIONS: RvD1-mediated inhibition of NETosis may represent a future medical treatment for the attenuation of AAA growth.
Asunto(s)
Antiinflamatorios/farmacología , Aorta Abdominal/efectos de los fármacos , Aneurisma de la Aorta Abdominal/prevención & control , Ácidos Docosahexaenoicos/farmacología , Trampas Extracelulares/efectos de los fármacos , Neutrófilos/efectos de los fármacos , Animales , Aorta Abdominal/metabolismo , Aorta Abdominal/patología , Aneurisma de la Aorta Abdominal/inducido químicamente , Aneurisma de la Aorta Abdominal/metabolismo , Aneurisma de la Aorta Abdominal/patología , Citrulinación , Citocinas/metabolismo , Modelos Animales de Enfermedad , Trampas Extracelulares/metabolismo , Histonas/metabolismo , Mediadores de Inflamación/metabolismo , Metaloproteinasa 2 de la Matriz/metabolismo , Ratones Endogámicos C57BL , Ratones Noqueados para ApoE , Neutrófilos/metabolismo , Neutrófilos/patología , Elastasa Pancreática , Remodelación Vascular/efectos de los fármacosRESUMEN
INTRODUCTION: The purpose of this study was to determine the long-term incidence of bone fracture after bariatric surgery, identify specific risk factors for fracture, and compare these data to baseline risk in a comorbidity-matched morbidly obese population. We hypothesize that, despite prior studies with conflicting results, bariatric surgery increases a patient's long-term risk of fracture. METHODS: All patients who underwent bariatric surgery at a single institution 1985-2015 were reviewed. Univariate analysis of patient demographic data including comorbidities, insurance payer status, procedure type, and BMI was performed. Multivariate logistic regression was used to identify independent predictors of fracture in this population. Finally, we identified a propensity-matched control group of morbidly obese patients from our institutional Clinical Data Repository in the same timeframe who did not undergo bariatric surgery to determine expected rate of fracture without bariatric surgery. RESULTS: A total of 3439 patients underwent bariatric surgery, with 220 (6.4%) patients experiencing a bone fracture at mean follow-up of 7.6 years. On multivariate logistic regression, independent predictors of increased fracture included tobacco use and Roux-en-Y gastric bypass while private insurance and race were protective (table). Additionally, 1:1 matching on all comorbidity and demographic factors identified 3880 patients (1940 surgical patients) with equal propensity to undergo bariatric surgery. Between the propensity-matched cohorts, patients who had a history of bariatric surgery were more than twice as likely to experience a fracture as those who did not (6.4 vs. 2.7%, p < 0.0001). CONCLUSIONS: This study of bariatric surgery patients at our institution identified several independent predictors of postoperative fracture. Additionally, these long-term data demonstrate patients who had bariatric surgery are at a significantly increased risk of bone fracture compared to a propensity-matched control group. Future efforts need to focus on nutrient screening and risk modification to reduce the impact of this long-term complication.
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Cirugía Bariátrica , Fracturas Óseas/etiología , Obesidad Mórbida/cirugía , Complicaciones Posoperatorias , Adulto , Femenino , Estudios de Seguimiento , Fracturas Óseas/epidemiología , Humanos , Incidencia , Modelos Logísticos , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/epidemiología , Estudios Retrospectivos , Factores de Riesgo , Resultado del TratamientoRESUMEN
BACKGROUND: New pediatric and vascular surgical fellowship programs decrease resident operative experience in those subspecialties in co-located general surgery programs.After 2 decades of increases, the mean number of endocrine surgery cases performed by general surgery residents nationally has decreased since 2010 to 2011. We hypothesized that new endocrine surgery fellowship programs lead to a decrease in the number of endocrine surgery cases performed by co-located general surgery residents and may be a contributing factor in the recent national decline in endocrine surgery cases performed by general surgery residents. METHODS: Endocrine surgery fellowship programs associated with a single, Accreditation Council of Graduate Medical Education-accredited general surgery program that have completed training of 1 fellow by the 2014-2015 academic year were identified. Endocrine surgery cases performed by general surgery residents who completed co-located general surgery programs from 2002 to 2003 through 2017 to 2018 were recorded. Descriptive statistics are shown as mean ± standard deviation. Statistical significance was calculated using the Mann-Whitney U Test. RESULTS: In the 13 general surgery programs with 5 years of case log data after the matriculation of the first fellow, the mean number of total endocrine surgery cases/resident increased from 47 ± 23 in year 0 to 57 ± 25 in year 5 (z-score = 2.53; P < .05). CONCLUSION: New endocrine surgery fellowship programs do not decrease the endocrine surgery cases performed by general surgery residents and have not contributed to the national decline in endocrine surgery cases by general surgery residents.
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Competencia Clínica/estadística & datos numéricos , Procedimientos Quirúrgicos Endocrinos/estadística & datos numéricos , Endocrinología/educación , Cirugía General/educación , Internado y Residencia/estadística & datos numéricos , Acreditación/estadística & datos numéricos , Procedimientos Quirúrgicos Endocrinos/educación , Endocrinología/organización & administración , Cirugía General/organización & administración , Humanos , Internado y Residencia/organización & administración , Cirujanos/educación , Cirujanos/estadística & datos numéricos , Carga de Trabajo/estadística & datos numéricosRESUMEN
BACKGROUND: The aim of this study was to determine trends in the experience of general surgery residents with endocrine surgery cases. METHODS: American Association of Endocrine Surgeons national general surgery case logs from 1989 through 2019 were reviewed. The numbers of individuals completing residency and the mean and median number of endocrine surgery cases by type and by level of operating resident surgeon were abstracted from annual data and analyzed. Descriptive statistics and linear regression analyses were performed modeling endocrine surgery cases over time and stratified by procedure type and resident level. RESULTS: The number of individuals completing general surgery residency each year increased from 981 to 1,219 (P < .001). The average total number of endocrine surgery cases performed increased from 17 to 33.2 (P < .001) but has declined since its peak at 36.9 in 2010 to 2011 (P = .014). Thyroid operations increased from 11.4 to 19.8 (P < .001) but peaked at 23.5 in 2010 to 2011 and have since declined (P < .001). Parathyroid operations more than doubled from 4.2 to 9.7 (P < .001). Adrenal operations increased from 1 to 2.2 (P < .001) and pancreatic endocrine operations increased from 0.2 to 1.5 (P < .001). Surgeon Chief endocrine surgery cases peaked at 14.4 in 2003 to 2004 but have since declined by 22.2% (P < .001). Surgeon Junior endocrine surgery cases increased overall (P < .001) but peaked at 22.8 in 2011 to 2012. There was increasing heterogeneity over time in trainee experience (P < .001). CONCLUSION: After having increased for 2 decades, the number of endocrine surgery cases performed by general surgery residents is currently in decline. Possible contributing factors include growth in the number of general surgery residents, variable and narrowed case mix, and encroachment by other learners.
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Procedimientos Quirúrgicos Endocrinos/educación , Procedimientos Quirúrgicos Endocrinos/tendencias , Cirugía General/educación , Internado y Residencia/tendencias , Competencia Clínica , Procedimientos Quirúrgicos Endocrinos/estadística & datos numéricos , Humanos , Estudios Longitudinales , Estados UnidosRESUMEN
INTRODUCTION: Given the unknown biologic antecedents before aortic aneurysm rupture, the purpose of this study was to establish a reproducible model of aortic aneurysm rupture. METHODS: We fed 7-week-old apolipoprotein E deficient mice a high-fat diet for 4 weeks and osmotic infusion pumps containing Angiotensin II were implanted. Angiotensin II was delivered continuously for 4 weeks at either 1,000 ng/kg/min (n = 25) or 2,000 ng/kg/min (n = 29). A third group (n = 14) were given Angiotensin II at 2,000 ng/kg/min and 0.2% ß-aminopropionitrile dissolved in drinking water. Surviving mice were killed 28 days after pump placement, aortic diameters were measured, and molecular analyses were performed. RESULTS: Survival at 28 days was significantly different among groups with 80% survival in the 1,000 ng/kg/min group, 52% in the 2,000 ng/kg/min group, and only 14% in the Angiotensin II/ß-aminopropionitrile group (P = .0001). Concordantly, rupture rates were statistically different among groups (8% versus 38% versus 79%, P < .0001). Rates of abdominal aortic aneurysm were 48%, 55%, and 93%, respectively, with statistically higher rates in the Angiotensin II/ß-aminopropionitrile group compared with both the 1,000 ng and 2,000 ng Angiotensin II groups (P = .006 and P = .0165, respectively). Rates of thoracic aortic aneurysm formation were 12%, 52%, and 79% in the 3 groups with a statistically higher rate in the Angiotensin II/ß-aminopropionitrile group compared with 1,000 ng group (P < .0001). CONCLUSIONS: A reproducible model of aortic aneurysm rupture was developed with a high incidence of abdominal and thoracic aortic aneurysm. This model should enable further studies investigating the pathogenesis of aortic rupture, as well as allow for targeted strategies to prevent human aortic aneurysm rupture.
Asunto(s)
Rotura de la Aorta , Modelos Animales de Enfermedad , Aminopropionitrilo , Angiotensina II , Animales , Aorta/metabolismo , Citocinas/metabolismo , Masculino , Ratones , Ratones Noqueados para ApoERESUMEN
Foreign body ingestion is one of the many potential causes of esophageal perforation. In this case report we describe a man who presented with chest pain and was found to have an isolated hemorrhagic pericardial effusion secondary to occult ingestion and pericardial migration of a metallic foreign body. Surgical management was successful, and the patient has recovered well.
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Cuerpos Extraños/complicaciones , Derrame Pericárdico/etiología , Cuerpos Extraños/cirugía , Humanos , Masculino , Derrame Pericárdico/cirugíaRESUMEN
BACKGROUND: Total abdominal colectomy (TAC) is the standard surgical treatment of Clostridium difficile infection (CDI). An alternative therapy, loop ileostomy and colonic lavage (IL), was described in 2011, but the results have never been validated. METHODS: Patients treated surgically for CDI between April 2011 and June 2015 were included. Bivariable analysis was used to compare 30-day mortality, 1-year mortality, CDI recurrence, colon preservation and ileostomy reversal. RESULTS: Ten IL patients and thirteen TAC patients were identified. 30-day mortality (30% vs 23%, p = 1.0) and 1-year mortality (40% vs 46%, p = 1.0) were similar. Four IL and three TAC patients (57% vs 30%, p = 0.35) experienced recurrent CDI. All six surviving IL patients had successful colon preservation; five underwent ileostomy reversal compared to three in the TAC group (83% vs 43%, p = 0.27). CONCLUSIONS: Although IL allowed colon preservation and return of intestinal continuity in most patients, IL did not decrease mortality or recurrent CDI when compared to TAC.