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Introduction: Defensive medicine is a medical practice in which health care providers' primary intent is to avoid criticism and lawsuits, rather than providing for patients' medical needs. The purpose of this study was to characterize medical students' exp

Background: Transversus abdominis plane blocks improve postoperative pain after colon and rectal resections, but the benefits of liposomal bupivacaine use for these blocks have not been clearly demonstrated., Objective: This study aimed to determine whether using liposomal bupivacaine in transversus abdominis plane blocks improves postoperative pain and reduces opioid use after colorectal surgery compared to standard bupivacaine., Design: This study was a single-blinded, single-institution, prospective randomized controlled trial comparing liposomal bupivacaine to standard bupivacaine in transversus abdominis plane blocks in patients undergoing elective colon and rectal resections., Settings: This study was conducted at a single-institution academic medical center with 6 staff colorectal surgeons and 2 colorectal surgery fellows., Patients: Ninety-six patients aged 18 to 85 years were assessed for eligibility; 76 were included and randomly assigned to 2 groups of 38 patients., Interventions: Patients in the experimental group received liposomal bupivacaine transversus abdominis plane blocks, whereas the control group received standard bupivacaine blocks., Main Outcome Measures: The primary outcome was maximum pain score on postoperative day 2. Secondary outcomes included daily maximum and average pain scores in the 3 days after surgery, as well as daily morphine milligram equivalent use and length of hospital stay., Results: Patients receiving liposomal bupivacaine blocks had lower maximum pain scores on the day of surgery (mean, 6.5 vs 7.7; p = 0.008). No other difference was found between groups with respect to maximum or average pain scores at any time point postoperatively, nor was there any difference in morphine milligram equivalents used or length of stay (median, 3.1 d)., Limitations: This was a single-institution study with only patients blinded to group assignment., Conclusions: Liposomal bupivacaine use in transversus abdominis plane blocks for patients undergoing laparoscopic colorectal resections does not seem to improve postoperative pain, nor does it reduce narcotic use or decrease length of stay. Given its cost, use of liposomal bupivacaine in transversus abdominis plane blocks is not justified for colon and rectal resections. See Video Abstract at http://links.lww.com/DCR/B979 ., Clinical Trial Registration: URL: http://www.clinicaltrials.gov . Identifier: NCT04781075., Bloqueos Tap De Bupivacana Liposomal En Resecciones Colorrectales Laparoscpicas Un Ensayo Controlado Aleatorio De Una Sola Institucin: ANTECEDENTES:Los bloqueos del plano transverso del abdomen, mejoran el dolor posoperatorio después de las resecciones de colon y recto, pero los beneficios del uso de bupivacaína liposomal para estos bloqueos, no se han demostrado claramente.OBJETIVO:Investigar la eficacia de la inyección con tejido adiposo autólogo recién recolectado en fístulas anales criptoglandulares complejas.DISEÑO:Ensayo controlado, aleatorio, prospectivo, simple ciego, de una sola institución, que compara la bupivacaína liposomal con la bupivacaína estándar en bloqueos del plano transverso del abdomen, en pacientes sometidos a resecciones electivas de colon y recto. Identificador de ClinicalTrials.gov : NCT04781075.ENTORNO CLINICO:Centro médico académico de una sola institución con seis cirujanos de plantilla y becarios de cirugía colorrectal.PACIENTES:Se evaluó la elegibilidad de 96 pacientes de 18 a 85 años; 76 fueron incluidos y aleatorizados en dos grupos de 38 pacientes.INTERVENCIONES:Los pacientes del grupo experimental recibieron bloqueos del plano transverso del abdomen con bupivacaína liposomal, mientras que el grupo de control recibió bloqueos de bupivacaína estándar.PRINCIPALES MEDIDAS DE VALORACION:El resultado primario fue la puntuación máxima de dolor en el segundo día posoperatorio. Los resultados secundarios incluyeron las puntuaciones máximas y medias diarias de dolor en los 3 días posteriores a la cirugía, así como el uso diario equivalente en miligramos de morfina y la duración de la estancia hospitalaria.RESULTADOS:Los pacientes que recibieron bloqueos de bupivacaína liposomal, tuvieron puntuaciones máximas de dolor más bajas, el día de la cirugía (media 6,5 frente a 7,7, p = 0,008). No hubo ninguna otra diferencia entre los grupos con respecto a las puntuaciones de dolor máximas o promedio en cualquier momento después de la operación, ni hubo ninguna diferencia en los equivalentes de miligramos de morfina utilizados o la duración de la estancia (mediana de 3,1 días).LIMITACIONES:Estudio de una sola institución con cegamiento de un solo paciente.CONCLUSIONES:El uso de bupivacaína liposomal en bloqueos del plano transverso del abdomen, para pacientes sometidos a resecciones colorrectales laparoscópicas, no parece mejorar el dolor posoperatorio, ni reduce el uso de narcóticos ni la duración de la estancia hospitalaria. Dado su costo, el uso de bupivacaína liposomal en bloqueos TAP no está justificado para resecciones de colon y recto. Consulte Video Resumen en http://links.lww.com/DCR/B797 . Traducción Dr. Fidel Ruiz Healy., (Copyright © The ASCRS 2022.)

The furthest extent of restorative proctectomy involves a colon to anal anastomosis in the deep pelvis. While the anastomosis can be challenging, it can allow the patient to avoid a permanent ostomy. Patient and surgeon preparation can improve patient outcomes. This article will describe the options, technical challenges, and anecdotal tips for coloanal anastomosis., Competing Interests: Conflict of Interest None declared., (Thieme. All rights reserved.)

Background: Interleukin-1 (IL-1) signaling has an established role as a cytokine signaling pathway important for progression of abdominal aortic aneurysms (AAAs). While the IL-1β ligand and IL-1R1 have been previously investigated, the role of the IL-1α ligand in AAAs remains unknown. In this study, we sought to examine the role of IL-1α in AAAs using genetic and pharmacologic approaches., Methods: Eight-week-old wild-type (WT) or IL-1α knock-out (KO) male and female mice (n = 10-16/group) underwent experimental AAA and were harvested 14 days following surgery to assess AAA size and characteristics. In separate studies, 8-week-old WT mice were treated with an inhibitor to IL-1α during AAA formation and harvested 14 days following surgery. Finally, WT and IL-1α KO mice were administered Anakinra, an IL-R1 inhibitor, during AAA formation to determine the effect of inhibiting IL-1R1 when IL-1α is knocked out., Results: Male and female IL-1α KO mice had larger AAAs compared to WT AAAs (male: 153% vs. 89.2%, P = 0.0001; female: 86.6% vs. 63.5%, P = 0.02). IL-1α KO mice had greater elastin breakage (P = 0.01), increased levels of macrophage staining (P = 0.0045), and greater pro-metallo proteinase 2 (P = 0.02). Pharmacologic inhibition of WT male mice with an IL-1α neutralizing antibody resulted in larger AAAs (133.1% vs. 77.0%, P < 0.001). Finally, treatment of IL-1α KO male mice with Anakinra decreased AAA formation compared with vehicle control AAAs (Anakinra + IL-1α KO: 47.7% vs. WT: 147.1%; P = 0.0001)., Conclusions: IL-1α disruption using either genetic or pharmacologic approaches worsens AAAs., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Large animal models to study abdominal aortic aneurysms are sparse. The purpose of this model is to create reproducible, clinically significant infrarenal abdominal aortic aneurysms (AAA) in swine. To achieve this, we use a combination of balloon angioplasty, elastase and collagenase, and a lysyl oxidase inhibitor, called β-aminopropionitrile (BAPN), to create clinically significant infrarenal aortic aneurysms, analogous to human disease. Noncastrated male swine are fed BAPN for 7 days prior to surgery to achieve a steady state in the blood. A midline laparotomy is performed and the infrarenal aorta is circumferentially dissected. An initial measurement is recorded prior to aneurysm induction with a combination of balloon angioplasty, elastase (500 units)/collagenase (8000 units) perfusion, and topical elastase application. Swine are fed BAPN daily until terminal procedure on either postoperative day 7, 14, or 28, at which time the aneurysm is measured, and tissue procured. BAPN + surgery pigs are compared to pigs that underwent surgery alone. Swine treated with BAPN and surgery had a mean aortic dilation of 89.9% ± 47.4% at day 7, 105.4% ± 58.1% at day 14, and 113.5% ± 30.2% at day 28. Pigs treated with surgery alone had significantly smaller aneurysms compared to BAPN + surgery animals at day 28 (p < 0.0003). The BAPN + surgery group had macroscopic and immunohistochemical evidence of end stage aneurysmal disease. Clinically significant infrarenal AAA can be induced using balloon angioplasty, elastase/collagenase perfusion and topical application, supplemented with oral BAPN. This model creates large, clinically significant AAA with hallmarks of human disease. This has important implications for the elucidation of AAA pathogenesis and testing of novel therapies and devices for the treatment of AAA. Limitations of the model include variation in BAPN ingested by swine, quality of elastase perfusion, and cost of BAPN.

According to the Center for Disease Control, aortic aneurysms (AAs) were considered a leading cause of death in all races and both sexes from 1999-2016. An aneurysm forms as a result of progressive weakening and eventual dilation of the aorta, which can rupture or tear once it reaches a critical diameter. Aneurysms of the descending aorta in the chest, called descending thoracic aortic aneurysms (dTAA), make up a large proportion of aneurysm cases in the United States. Uncontained dTAA rupture is almost universally lethal, and elective repair has a high rate of morbidity and mortality. The purpose of our model is to study dTAA specifically, to elucidate the pathophysiology of dTAA and to search for molecular targets to halt the growth or reduce the size of dTAA. By having a murine model to study thoracic pathology precisely, targeted therapies can be developed to specifically test dTAA. The method is based on the placement of porcine pancreatic elastase (PPE) directly on the outer murine aortic wall after surgical exposure. This creates a destructive and inflammatory reaction, which weakens the aortic wall and allows for aneurysm formation over weeks to months. Though murine models possess limitations, our dTAA model produces robust aneurysms of predictable size. Furthermore, this model can be used to test genetic and pharmaceutical targets which may arrest dTAA growth or prevent rupture. In human patients, interventions such as these could help avoid aneurysm rupture, and difficult surgical intervention.

Objective: Few large-animal models exist for the study of aortic aneurysms. β-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., (Copyright © 2018 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Objective- The goal of this study was to determine the role of ZFP148 (zinc-finger protein 148) in aneurysm formation. Approach and Results- ZFP148 mRNA expression increased at day 3, 7, 14, 21, and 28 after during abdominal aortic aneurysm formation in C57BL/6 mice. Loss of ZFP148 conferred abdominal aortic aneurysm protection using ERTCre+ ZFP148 flx/flx mice. In a third set of experiments, smooth muscle-specific loss of ZFP148 alleles resulted in progressively greater protection using novel transgenic mice (MYH [myosin heavy chain 11] Cre+ flx/flx, flx/wt, and wt/wt). Elastin degradation, LGAL3, and neutrophil staining were significantly attenuated, while α-actin staining was increased in ZFP148 knockout mice. Results were verified in total cell ZFP148 and smooth muscle-specific knockout mice using an angiotensin II model. ZFP148 smooth muscle-specific conditional mice demonstrated increased proliferation and ZFP148 was shown to bind to the p21 promoter during abdominal aortic aneurysm formation. ZFP148 smooth muscle-specific conditional knockout mice also demonstrated decreased apoptosis as measured by decreased cleaved caspase-3 staining. ZFP148 bound smooth muscle marker genes via chromatin immunoprecipitation analysis mediated by NF-1 (neurofibromin 1) promote histone H3K4 deacetylation via histone deacetylase 5. Transient transfections and chromatin immunoprecipitation analyses demonstrated that NF-1 was required for ZFP148 protein binding to smooth muscle marker genes promoters during aneurysm formation. Elimination of NF-1 using shRNA approaches demonstrated that NF-1 is required for binding and elimination of NF-1 increased BRG1 recruitment, the ATPase subunit of the SWI/SWF complex, and increased histone acetylation. Conclusions- ZFP148 plays a critical role in multiple murine models of aneurysm formation. These results suggest that ZFP148 is important in the regulation of proliferation, smooth muscle gene downregulation, and apoptosis in aneurysm development.

Background: Approximately half of Crohn's patients require intestinal resection, and many need repeat resections., Objective: The purpose of this study was to evaluate the increased risk of clinical anastomotic leak in patients with a history of previous intestinal resection undergoing repeat resection with anastomosis for Crohn's disease., Design: This was a retrospective analysis of prospectively collected departmental data with 100% capture., Settings: The study was conducted at the department of colorectal surgery in a tertiary care teaching hospital between July 2007 and March 2016., Patients: A cohort of consecutive patients with Crohn's disease who were treated with intestinal resection and anastomosis, excluding patients with proximal fecal diversion, were included. The cohort was divided into 2 groups, those with no previous resection compared with those with previous resection., Main Outcome Measures: Clinical anastomotic leak within 30 days of surgery was measured., Results: Of the 206 patients who met criteria, 83 patients had previous intestinal resection (40%). The 2 groups were similar in terms of patient factors, immune-suppressing medication use, and procedural factors. Overall, 20 clinical anastomotic leaks were identified (10% leak rate). There were 6 leaks (5%) detected in patients with no previous intestinal resection and 14 leaks (17%) detected in patients with a history of previous intestinal resection (p < 0.005). The OR of anastomotic leak in patients with Crohn's disease with previous resection compared with no previous resection was 3.5 (95% CI, 1.3-9.4). Patients with 1 previous resection (n = 53) had a leak rate of 13%, whereas patients with ≥2 previous resections (n = 30) had a leak rate of 23%. The number of previous resections correlated with increasing risk for clinical anastomotic leak (correlation coefficient = 0.998)., Limitations: This was a retrospective study with limited data to perform a multivariate analysis., Conclusions: Repeat intestinal resection in patients with Crohn's disease is associated with an increased rate of anastomotic leakage when compared with initial resection despite similar patient, medication, and procedural factors. See Video Abstract at http://links.lww.com/DCR/A459.

Objective: Many patients with aortic dissection develop Crawford extent I or II thoracoabdominal aortic aneurysms (TAAA). Because open repair is associated with a high morbidity and mortality, hybrid approaches to TAAA repair are emerging. In this study, we evaluated the midterm outcomes and aortic remodeling of a hybrid technique that combines proximal thoracic endovascular aneurysm repair (TEVAR), followed by staged distal open thoracoabdominal repair for patients with Crawford extent I or II TAAAs secondary to chronic aortic dissection., Methods: We identified 19 patients with Crawford extent I (n = 1) or extent II (n = 18) TAAAs secondary to chronic aortic dissection who underwent a staged hybrid repair from 2007 to 2014 at our institution. Nine patients had previous open ascending aortic surgery for type I aortic dissection. Stage 1 TEVAR was performed via percutaneous (n = 8), femoral cutdown (n = 8), or iliac exposure (n = 3). The left subclavian artery was covered in nine patients and revascularized in eight patients using carotid-subclavian bypass (n = 7) or laser fenestration (n = 1). Stage 2 open repair was performed a median of 18 weeks later with partial cardiopulmonary bypass via left femoral arterial and venous cannulation for visceral and lower body perfusion. The open thoracoabdominal graft was anastomosed proximally in an end to end fashion with the endograft. We then assessed surgical morbidity and mortality, midterm survival, and freedom from reintervention. Aortic remodeling was measured and change in maximum aortic and false lumen diameter at last follow-up (median, 3 years) from baseline was assessed., Results: There were no deaths, strokes, or chronic renal failure in this cohort. After stage 1 TEVAR, three patients required repeat intervention for endoleak (type Ia, n = 1; type Ib, n = 1; type II, n = 1) before open repair. After stage 2 open repair, there was a single delayed permanent paralysis 2 weeks after discharge. At a median 3-year follow-up (range, 6 months-6.2 years), there were no deaths, neurologic events, endoleaks, or TAAA reinterventions. Complete false lumen thrombosis occurred in 100% of the patients, with maximum false lumen diameter decreasing from 34.3 ± 15.3 mm to 13.2 ± 12.0 mm (P < .01) and total aortic diameter decreasing from 60.2 ± 9.0 mm to 49.4 ± 9.6 mm (P < .01)., Conclusions: Staged hybrid TAAA repair, using a combination of proximal TEVAR with open distal repair, can be performed using established endovascular skills and technology coupled with traditional open aortic surgical techniques, with low surgical morbidity and mortality. In the midterm, staged hybrid TAAA repair was associated favorable survival, aortic remodeling, and freedom from reintervention., (Copyright © 2016 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Background: The herpes B virus is a zoonotic agent that is endemic among macaque monkeys only, but can cause fatal encephalomyelitis in humans., Case Report: A 26-year-old female presented to a U.S. emergency department after being bitten by a wild macaque monkey. The emergency medicine team administered rabies immunoglobulin and rabies vaccine. The team also prescribed acyclovir for prophylactic coverage against herpes B, a deadly zoonotic agent that is endemic among macaque monkeys. A discussion of background, exposure, transmission, symptoms, treatment for herpes B, including latest data available, literature, and Centers for Disease Control and Prevention guidelines are included. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Zoonotic exposures can cause infectious diseases, which are unfamiliar and deadly. The emergency physician's knowledge of the association between the deadly herpes B infection and wild macaque monkey may expedite treatment and be instrumental in patient morbidity and survival., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: Thoracic aortic aneurysms (TAA) and abdominal aortic aneurysms (AAA) represent related but distinct disease processes. Interleukin-6 (IL-6) is known to be significantly upregulated in human TAA and AAA. We hypothesize that loss of IL-6 is protective in experimental TAA and AAA., Methods: Murine TAAs or AAAs were created using a novel model in C57/B6 mice by treating the intact aorta with elastase. Cytokine profiles were analyzed with antibody arrays (n = 5 per group). Separately, to determine the role of IL-6, thoracic (n = 7) or abdominal (n = 7) aortas of wild type mice and IL-6 knockout (KO) mice were treated with elastase. Additionally, thoracic animals treated with either the IL-6 receptor antagonist tocilizumab (n = 8) or vehicle (n = 5). Finally, human TAA and AAA were analyzed with human cytokine array., Results: Elastase treatment of thoracic aortas yielded dilation of 86.8% ± 9.6%, and abdominal aortas produced dilation of 85.6% ± 16.2%. Murine IL-6, CXCL13, and matrix metalloproteinase-9 were significantly elevated in TAA compared with AAA (p = 0.004, 0.028, and 0.001, respectively). The IL-6KO mice demonstrated significantly smaller TAA size relative to wild type mice (wild type 100.1% versus IL-6KO 76.5%, p = 0.04). The IL-6KO mice did not show protection from AAA (p = 0.732). Pharmacologic inhibition of IL-6 resulted in significant reduction in TAA size (tocilizumab 71.5% ± 13.2% versus vehicle 103.6% ± 20.7%, p = 0.005). Human TAA showed significantly greater IL-6 (p < 0.0001) compared with AAA and normal thoracic and abdominal aorta., Conclusions: Interleukin-6 is significantly greater in both murine and human TAA compared with AAA, suggesting fundamental differences in these disease processes. Interleukin-6 receptor antagonism attenuates experimental TAA formation, indicating that IL-6 may be a potential target for human thoracic aneurysmal disease., (Copyright © 2015 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Outcomes for lung transplantation are the worst of any solid organ, and ischemia-reperfusion injury (IRI) limits both short- and long-term outcomes. Presently no therapeutic agents are available to prevent IRI. Sphingosine 1-phosphate (S1P) modulates immune function through binding to a set of G protein-coupled receptors (S1PR1-5). Although S1P has been shown to attenuate lung IRI, the S1P receptors responsible for protection have not been defined. The present study tests the hypothesis that protection from lung IRI is primarily mediated through S1PR1 activation. Mice were treated with either vehicle, FTY720 (a nonselective S1P receptor agonist), or VPC01091 (a selective S1PR1 agonist and S1PR3 antagonist) before left lung IR. Function, vascular permeability, cytokine expression, neutrophil infiltration, and myeloperoxidase levels were measured in lungs. After IR, both FTY720 and VPC01091 significantly improved lung function (reduced pulmonary artery pressure and increased pulmonary compliance) vs. vehicle control. In addition, FTY720 and VPC01091 significantly reduced vascular permeability, expression of proinflammatory cytokines (IL-6, IL-17, IL-12/IL-23 p40, CC chemokine ligand-2, and TNF-α), myeloperoxidase levels, and neutrophil infiltration compared with control. No significant differences were observed between VPC01091 and FTY720 treatment groups. VPC01091 did not significantly affect elevated invariant natural killer T cell infiltration after IR, and administration of an S1PR1 antagonist reversed VPC01091-mediated protection after IR. In conclusion, VPC01091 and FTY720 provide comparable protection from lung injury and dysfunction after IR. These findings suggest that S1P-mediated protection from IRI is mediated by S1PR1 activation, independent of S1PR3, and that selective S1PR1 agonists may provide a novel therapeutic strategy to prevent lung IRI., (Copyright © 2015 the American Physiological Society.)

Objective: The protective effects of female gender on the development of abdominal aortic aneurysms (AAAs) have been attributed to anti-inflammatory effects of estrogen. Estrogen synthesis is dependent on the enzyme aromatase, which is located both centrally in the ovaries and peripherally in adipose tissue, bone, and vascular smooth muscle cells. It is hypothesized that deletion of aromatase in both ovarian and peripheral tissues would diminish the protective effect of female gender and would be associated with increased aortic diameter in female mice., Methods: Male and female 8- to 10-week-old mice with aromatase (wild type: WT) and without aromatase (ArKO) underwent elastase aortic perfusion with aortic harvest 14 days following. For the contribution of central and peripheral estrogen conversion to be evaluated, female WT mice were compared with female WT and ArKO mice that had undergone ovariectomy (ovx) at 6 weeks followed by elastase perfusion at 8 to 10 weeks. At aortic harvest, maximal aortic dilation was measured and samples were collected for immunohistochemistry and protein analysis. Serum was collected for serum estradiol concentrations. Groups were compared with analysis of variance. Human and mouse AAA cross sections were analyzed with confocal immunohistochemistry for aromatase, smooth muscle markers, and macrophage markers., Results: Female WT mice had significant reduction in aortic dilation compared with male WT mice (F WT, 51.5% ± 15.1% vs M WT, 78.7% ± 14.9%; P < .005). The protective effects of female gender were completely eliminated with deletion of aromatase (F ArKO, 82.6% ± 13.8%; P < .05 vs F WT). Ovariectomy increased aortic dilation in WT mice (F WT ovx, 70.6% ± 11.7%; P < .05 vs F WT). Aromatase deletion with ovariectomy further increased aortic dilation compared with WT ovx mice (F ArKO ovx, 87.3% ± 14.7%, P < .001 vs F WT and P < .05 vs F WT ovx). Accordingly, female ArKO ovx mice had significantly higher levels of the proinflammatory cytokines monocyte chemoattractant protein 1 and interleukin-1β and were associated with increased macrophage staining and decreased elastin staining. Regarding serum hormone levels, decreasing estradiol levels correlated with increasing aortic diameter (R = -0.565; P < .01). By confocal immunohistochemistry, both human and mouse AAA smooth muscle cells (smooth muscle α-actin positive) and macrophages (CD68 positive or Mac-2 positive) expressed aromatase., Conclusions: The protective effect of female gender on AAAs is due to estrogen synthesis and requires the presence of both ovarian and extragonadal/peripheral aromatase. Peripheral estrogen synthesis accounts for roughly half of the protective effect of female gender. If peripheral aromatase could be targeted, high levels of local estrogen could be produced and may avoid the side effects of systemic estrogen., (Copyright © 2015 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Recent reports of rupture in patients with abdominal aortic aneurysm (AAA) receiving B-cell depletion therapy highlight the importance of understanding the role of B cells (B1 and B2 subsets) in the development of AAA. We hypothesized that B2 cells aggravate experimental aneurysm formation. The IHC staining revealed infiltration of B cells in the aorta of wild-type (C57BL/6) mice at day 7 after elastase perfusion and persisted through day 21. Quantification of immune cell types using flow cytometry at day 14 showed significantly greater infiltration of mononuclear cells, including B cells (B2: 93% of total B cells) and T cells in elastase-perfused aortas compared with saline-perfused or normal aortas. muMT (mature B-cell deficient) mice were prone to AAA formation similar to wild-type mice in two different experimental AAA models. Contradicting our hypothesis, adoptive transfer of B2 cells suppressed AAA formation (102.0% ± 7.3% versus 75.2% ± 5.5%; P < 0.05) with concomitant increase in the splenic regulatory T cell (0.24% ± 0.03% versus 0.92% ± 0.23%; P < 0.05) and decrease in aortic infiltration of mononuclear cells. Our data suggest that B2 cells constitute the largest population of B cells in experimental AAA. Furthermore, B2 cells, in the absence of other B-cell subsets, increase splenic regulatory T-cell population and suppress AAA formation.

Background: Thoracic aortic aneurysms (TAAs) are common, but experimental TAA models are limited and the role of interleukin-1β (IL-1β) is undetermined., Methods and Results: IL-1β protein was measured in human TAAs and control aortas, and IL-1β protein was increased ≈20-fold in human TAAs. To develop an experimental model of TAAs, 8- to 10-week-old male C57Bl/6 mice (wild type [WT]) underwent thoracotomy with application of periadventitial elastase (WT TAA) or saline (WT control; n=30 per group). Elastase treatment to thoracic aortas resulted in progressive dilation until day 14 with maximal dilation of 99.6±24.7% compared with 14.4±8.2% for WT saline control (P<0.0001). WT TAAs demonstrated elastin fragmentation, smooth muscle cell loss, macrophage infiltration, and increased IL-1β expression. Next, TAAs were induced in mice deficient of IL-1β (IL-1β knockout) or IL-1 receptor (IL-1R knockout; n=10 each). Genetic deletion of IL-1β and IL-1R significantly decreased thoracic aortic dilation (IL-1β knockout=54.2±16.8% and IL-1R knockout=62.6±17.2% versus WT TAA=104.7±23.8%; P<0.001for both). IL-1β knockout and IL-1R knockout aortas demonstrated preserved elastin and smooth muscle cells with fewer inflammatory cells. Correspondingly, IL-1β and IL-1R knockout aortas had decreased inflammatory cytokine and matrix metalloproteinase 9 expression. Separately, WT mice pretreated with either IL-1R antagonist anakinra (100 mg/kg per day) or vehicle alone (control) underwent elastase treatment. Pretreatment of WT mice with anakinra attenuated TAA formation (control: 99.2±15.5% versus anakinra: 68.3±19.2%; P<0.005). Finally, to investigate treatment of small TAAs, WT mice were treated with anakinra 3 days after TAA induction. Anakinra treatment in WT mice with small TAAs reduced aortic dilation on day 14 (control treatment: 89.1±18.6% versus anakinra treatment: 59.7±25.7%; P=0.01)., Conclusions: Periadventitial application of elastase to murine thoracic aortas reproducibly produced aneurysms with molecular and histological features consistent with TAA disease. Genetic and pharmacological inhibition of IL-1β decreased TAA formation and progression, indicating that IL-1β may be a potential target for TAA treatment., (© 2014 American Heart Association, Inc.)

Introduction: Defensive medicine is a medical practice in which health care providers' primary intent is to avoid criticism and lawsuits, rather than providing for patients' medical needs. The purpose of this study was to characterize medical students' exposure to defensive medicine during medical school rotations., Methods: We performed a cross-sectional survey study of medical students at the beginning of their third year. We gave students Likert scale questionnaires, and their responses were tabulated as a percent with 95% confidence interval (CI)., Results: Of the 124 eligible third-year students, 102 (82%) responded. Most stated they rarely worried about being sued (85.3% [95% CI=77.1% to 90.9%]). A majority felt that faculty were concerned about malpractice (55.9% [95% CI=46.2% to 65.1%]), and a smaller percentage stated that faculty taught defensive medicine (32.4% [95% CI=24.1% to 41.9%]). Many students believed their satisfaction would be decreased by MC and lawsuits (51.0% [95% CI=41.4% to 60.5%]). Some believed their choice of medical specialty would be influenced by MC (21.6% [95% CI=14.7% to 30.5%]), and a modest number felt their enjoyment of learning medicine was lessened by MC (23.5% [95% CI=16.4% to 32.6%]). Finally, a minority of students worried about practicing and learning procedures because of MC (16.7% [95% CI=10.7% to 25.1%])., Conclusion: Although third-year medical students have little concern about being sued, they are exposed to malpractice concerns and taught considerable defensive medicine from faculty. Most students believe that fear of lawsuits will decrease their future enjoyment of medicine. However, less than a quarter of students felt their specialty choice would be influenced by malpractice worries and that malpractice concerns lessened their enjoyment of learning medicine. [West J Emerg Med. 2014;15(3):293-298.].

Background: The purpose of these experiments was to test the hypothesis that dietary phytoestrogens would diminish experimental aortic aneurysm formation., Materials and Methods: Six-wk-old C57BL/6 mice were divided into groups, fed either a diet with minimal phytoestrogen content or a regular commercial rodent diet with high phytoestrogen content for 2 wk. At the age of 8 wk, aortic aneurysms were induced by infusing the isolated infrarenal abdominal aorta with 0.4% elastase for 5 min. Mice were recovered and the diameter of the infused aorta was measured at postoperative days 3, 7, and 14. Abdominal aorta samples were collected for histology, cytokine array, and gelatin zymography after aortic diameter measurement. Blood samples were also collected to determine serum phytoestrogens and estradiol levels. Multiple-group comparisons were done using an analysis of variance with post hoc Tukey tests., Results: Compared with mice on a minimal phytoestrogen diet, mice on a regular rodent diet had higher levels of serum phytoestrogens (male, 1138 ± 846 ng/dL; female, 310 ± 295 ng/dL). These serum phytoestrogen levels were also much higher than their own endogenous estradiol levels (109-fold higher for males and 35.5-fold higher for females). Although aortic diameters of female mice were unaffected by the phytoestrogen concentration in the diets, male mice on the regular rodent diet (M+ group) developed smaller aortic aneurysms than male mice on the minimal phytoestrogen diet (M- group) on postoperative day 14 (M+ 54.8 ± 8.8% versus M- 109.3 ± 37.6%; P < 0.001). During aneurysm development (postoperative days 3 and 7), there were fewer neutrophils, macrophages, and lymphocytes in the aorta from the M+ group than from the M- group. Concentrations of multiple proinflammatory cytokines (matrix metalloproteinases [MMPs]; interleukin 1β [IL-1β]; IL-6; IL-17; IL-23; monocyte chemoattractant protein-1; regulated on activation, normal T cell expressed and secreted; interferon γ; and tumor necrosis factor α) from aortas of the M+ group were also lower than those from the aortas of the M- group. Zymography also demonstrated that the M+ group had lower levels of aortic MMP-9s than the M- group on postoperative day 14 (P < 0.001 for pro-MMP-9, P < 0.001 for active MMP-9)., Conclusions: These results suggest that dietary phytoestrogens inhibit experimental aortic aneurysm formation in male mice via a reduction of the inflammatory response in the aorta wall. The protective effect of dietary phytoestrogens on aneurysm formation warrants further investigation., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background: A source of frustration during laparoscopic cholecystectomy involves extraction of the gallbladder through port sites smaller than the gallbladder itself. We describe the development and testing of a novel device for the safe, minimal enlargement of laparoscopic port sites to extract large, stone-filled gallbladders from the abdomen., Methods: The study device consists of a handle with a retraction tongue to shield the specimen and a guide for a scalpel to incise the fascia within the incision. Patients enrolled underwent laparoscopic cholecystectomy. Gallbladder extraction was attempted. If standard measures failed, the device was implemented. Extraction time and device utility scores were recorded for each patient. Patients returned 3-4 weeks postoperatively for assessment of pain level, cosmetic effect, and presence of infectious complications., Results: Twenty (51 %) of 39 patients required the device. Average extraction time for the first eight patients was 120 s. After interim analysis, an improved device was used in 12 patients and average extraction time was 24 s. There were no adverse events. Postoperative pain ratings and incision cosmesis were comparable between patients with and without use of the device., Conclusion: The study device enables safe and rapid extraction of impacted gallbladders through the abdominal wall.

A 52-year-old patient presented with chronic substernal chest pain 18 months following exclusion of an inferior vena cava (IVC) filter with a self-expanding IVC stent. After a thorough work-up revealed no other possible cause of chest pain, the filter and stent were removed with subsequent resolution of chest pain. Intraoperatively, filter struts were found to have penetrated the posteromedial wall of the IVC and were abutting the periaortic neural plexus. Referred chest pain due to strut penetration of the caval wall is a novel complication of both IVC filters and IVC stents, demonstrating a need for continued surveillance., (Copyright © 2014 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Objective: Descending thoracic aortic diseases may be treated with either open thoracic aortic repair or thoracic endovascular aortic repair (TEVAR). Previous studies have demonstrated that race and socioeconomic status (SES) affect access to care and treatment allocation in vascular surgery. We hypothesized that racial minorities and lower SES patients have decreased propensity to have their thoracic aortic disease treated with TEVAR., Methods: Weighted discharge records for patients who underwent either open thoracic aortic repair or TEVAR between 2005 and 2008 were evaluated using the Nationwide Inpatient Sample. Patient records were stratified by therapeutic intervention (open repair vs TEVAR). Differences in baseline comorbidities, race, and SES were compared. To account for the effects of comorbidities and other factors, hierarchical logistic regression modeling was used to determine the likelihood for TEVAR performance based on differences in patients' race and SES., Results: A total of 60,784 thoracic repairs were analyzed, the majority (79.4%) of which were open repairs. The most common race was white (78.2%), followed by black (9.1%), Hispanic (5.7%), Asian or Pacific Islander (2.9%), and Native American (0.7%). Patients were divided into quartiles according to SES with 20.6% of patients in the lowest SES quartile, 24.3% in the second quartile, 26.4% in the third quartile, and 28.8% in the highest SES quartile. Indications for treatment were similar for both treatment groups. After adjusting for multiple patient and hospital factors, race and SES were significantly associated with treatment modality for thoracic aortic disease. Black, Hispanic, and Native American populations had increased adjusted odds ratios of TEVAR performance compared with white patients. Similarly, lower SES correlated with increased use of TEVAR., Conclusions: Contrary to our initial hypothesis, racial minorities (Black, Hispanic, and Native American) and patients with lower median household incomes have a greater association with the performance for TEVAR after accounting for patient comorbid disease, indication for treatment, payer status, and hospital volume. These results indicate that traditional racial disparities do not persist in TEVAR allocation., (Copyright © 2013. Published by Mosby, Inc.)

Background: KLF4 mediates inflammatory responses after vascular injury/disease; however, the role of KLF4 in abdominal aortic aneurysms (AAAs) remains unknown. The goals of the present study were to (1) determine the role of KLF4 in experimental AAA; and (2) determine the effect of KLF4 on smooth muscle (SM) cells in AAAs., Methods and Results: KLF4 expression progressively increased at days 3, 7, and 14 after aortic elastase perfusion in C57BL/6 mice. Separately, loss of a KLF4 allele conferred AAA protection using ERTCre+ KLF4 flx/wt mice in the elastase AAA model. In a third set of experiments, SM-specific loss of 1 and 2 KLF4 alleles resulted in progressively greater protection using novel transgenic mice (MYHCre+ flx/flx, flx/wt, and wt/wt) in the elastase AAA model compared with control. Elastin degradation, MAC2, and cytokine production (MCP1, tumor necrosis factor-α, and interleukin-23) were significantly attenuated, whereas α-actin staining was increased in KLF4 knockout mice versus controls. Results were verified in global KLF4 and SM-specific knockout mice using an angiotensin II model of aneurysm formation. KLF4 inhibition with siRNA attenuated downregulation of SM gene expression in vitro, whereas in vivo studies demonstrated that KLF4 binds to promoters of SM genes by chromatin immunoprecipitation analysis. Finally, human aortic aneurysms demonstrated significantly higher KLF4 expression that was localized to SM cells., Conclusions: KLF4 plays a critical role in aortic aneurysm formation via effects on SM cells. These results suggest that KLF4 regulates SM cell phenotypic switching and could be a potential therapeutic target for AAA disease.

Objective: Abdominal aortic aneurysms (AAAs) are common, but their exact pathogenesis remains unknown and no specific medical therapies are available. We sought to evaluate interleukin-1β (IL-1β) and interleukin-1 receptor (IL-1R) in an experimental AAA model to identify novel therapeutic targets for AAA treatment., Methods and Results: IL-1β mRNA and protein levels were significantly elevated in abdominal aortas of 8- to 12-week-old male C57Bl/6 mice after elastase aortic perfusion (wild-type [WT]) compared with saline perfusion. Mice with genetic deletion of IL-1β (IL-1β knockout [KO]) or IL-1R (IL-1R KO) that underwent elastase perfusion demonstrated significant protection against AAA formation, with maximal aortic dilations of 38.0±5.5% for IL-1β KO and 52.5±4.6% for IL-1R KO, compared with 89.4±4.0% for WT mice (P<0.005). Correspondingly, IL-1β KO and IL-1R KO aortas had reduced macrophage and neutrophil staining with greater elastin preservation compared with WT. In WT mice pretreated with escalating doses of the IL-1R antagonist anakinra, there was a dose-dependent decrease in maximal aortic dilation (R=-0.676; P<0.0005). Increasing anakinra doses correlated with decreasing macrophage staining and elastin fragmentation. Lastly, WT mice treated with anakinra 3 or 7 days after AAA initiation with elastase demonstrated significant protection against AAA progression and had decreased aortic dilation compared with control mice., Conclusions: IL-1β is critical for AAA initiation and progression, and IL-1β neutralization through genetic deletion or receptor antagonism attenuates experimental AAA formation. Disrupting IL-1β signaling offers a novel pathway for AAA treatment.

Contrast angiography with carbon dioxide (CO2) is frequently used in patients with renal dysfunction or iodinated contrast allergies, as CO2 is nonallergenic, nontoxic, and rapidly absorbed in the blood. However, when delivered intra-arterially, there is a possibility that CO2 may create a vapor lock with resultant transient ischemia. We describe a case of suspected CO2 embolus to the iliolumbar artery after iliac artery stenting resulting in immediate loss of bilateral lower extremity motor and sensory function. After placement of a spinal drain and elevation of mean arterial blood pressure, the patient had complete return of sensation with improvement in motor function., (Copyright © 2012 Society for Vascular Surgery. Published by Mosby, Inc. All rights reserved.)

Objective: Repair of patients with extent I and II thoracoabdominal aortic aneurysms (TAAAs) is associated with significant morbidity and mortality, whereas repair of more distal extent III and IV TAAAs has a lower risk of paraplegia and death. Therefore, we describe an approach using thoracic endovascular aneurysm repair (TEVAR) as the index operation to convert extent I and II TAAAs to extent III and IV TAAAs amenable to subsequent open aortic repair to minimize patient risk., Methods: Between July 2007 and March 2012, 10 staged hybrid operations were performed to treat one extent I and nine extent II TAAAs. Aortic aneurysm pathology included five chronic type B dissections, three acute type B dissections, and two penetrating aortic ulcers. Initially, the proximal descending thoracic aorta was repaired with TEVAR for coverage of the most proximal fenestration or penetrating ulcer, with seven elective and three emergent repairs. Interval open distal aortic replacement was performed in a short-term planned setting or for progressive dilation of the distal aortic segment. In the open repair, the proximal end of the graft was sewn directly to the distal end of the TEVAR and outer wall of the aorta., Results: Average patient age was 48 years, and 60% were men. Risk factors included hypertension (80%), current tobacco use (50%), and Marfan syndrome (30%). Complications after TEVAR included type IA (n=1) and type II (n=3) endoleaks, pleural effusions (n=3), and acute kidney injury (n=1). Three patients required endovascular reinterventions. In patients with dissection, persistent filling of the false lumen was common and associated with distal thoracic aortic dilation. Complications of open repair included acute kidney injury in two patients, but no cardiac, pulmonary, or neurologic morbidity. Median time between TEVAR and open repair was 14 weeks. Most importantly, no deaths or neurologic deficits occurred after either procedure during a median follow-up of 35 weeks., Conclusions: A staged hybrid approach to extensive TAAAs combining proximal TEVAR, followed by interval open distal TAAA repair, is safe and appears to be an effective alternative to traditional open repair. This approach may decrease the significant morbidity associated with single-stage open extent I and II TAAA repairs and may be applicable to multiple TAAA etiologies., (Copyright © 2012 Society for Vascular Surgery. Published by Mosby, Inc. All rights reserved.)

Objective: Autologous greater saphenous vein (GSV) graft is frequently used as a conduit during arterial bypass. Preoperative vein mapping has been traditionally used to assess conduit adequacy and define GSV anatomy, thereby decreasing operative time and reducing wound complications. The purpose of this study was to determine whether GSV mapping using computed tomography angiography (CTA) closely correlated with that of traditional duplex ultrasonography (US)., Methods: From August 2009 through June 2011, 88 limbs from 51 patients underwent CTA of the lower extremities for the purpose of defining arterial anatomy with concurrent US for preoperative vein mapping. GSV diameters were measured by two blinded reviewers on CTA (both antero-posterior [AP] and lateral dimensions) and compared with US-based measurements at levels of the proximal thigh, mid-thigh, knee, mid-calf, and ankle. CTA and US measurements were compared at each anatomic level using linear regression. Statistical analysis was performed using SPSS software. Charge reduction was calculated based on technical and professional fees for each imaging study., Results: GSV diameter sequentially decreased from the proximal thigh to the mid-calf and then increased to the ankle as measured by CTA and US. CTA-based measurements of the GSV significantly correlated with US GSV diameters (R = 0.927 [lateral dimension], 0.922 [AP dimension]; P < .005). The strongest degree of correlation occurred in measurements at the proximal thigh, followed by the mid-thigh, mid-calf, knee, and ankle. GSV measurement by CTA was over 90% sensitive and accurate for detecting appropriate GSV diameter for bypass (diameter >2.0 mm). Eliminating preoperative US vein mapping for the study patients at our institution would have resulted in charge reductions of $49,316 over the study period., Conclusions: Indirect venography by CTA correlates well with US for GSV mapping in the lower extremity and offers significant reduction in imaging-related preoperative charges. CTA is sensitive and accurate for detecting GSVs that are appropriate for bypass. Furthermore, CTA allows AP and lateral evaluation of the GSV throughout its anatomic course. As CTA is often performed prior to arterial bypass, indirect evaluation of the GSV using preoperative CTA should be considered a promising alternative to the use of US., (Copyright © 2012 Society for Vascular Surgery. Published by Mosby, Inc. All rights reserved.)

Although there is still a role for conventional sternotomy for aortic valve replacement, minimally invasive techniques are increasing in popularity and may benefit the patient with shorter postoperative course, less morbidity, and decreased overall cost. Additionally, transcatheter procedures have recently shown promising results in high-risk patients. This article provides an overview of the development of minimally invasive aortic valve operations, including a brief history of minimally invasive approaches, surgical considerations during minimally invasive aortic valve replacement, and the technical approach to performing a hemisternotomy with aortic valve replacement. In addition, the authors review transcatheter techniques, including aortic valve replacement via a sheath placed in the apex of the left ventricle or through a sheath placed in the femoral vessels. Finally, the exciting results of the PARTNER trial and the effect of these results on the future of aortic valve surgery are discussed.

Background: Intractable nonvariceal upper gastrointestinal bleeding (UGIB) is associated with significant morbidity and mortality. Endovascular therapy is an alternative to surgery for high-risk patients., Materials and Methods: Review of prospectively collected data from patients who underwent emergent gastroduodenal artery embolization for UGIB., Results: Eight patients (mean age 68.5 years) were identified. They all had significant comorbidities and were deemed to be at high risk for surgical intervention. Endoscopy was performed in 7 patients. Active extravasation was present at the time of embolization in 5 (62.5%) patients. The technical success and clinical response rates were each 100%. The 30-day mortality rate was 12.5%. [corrected] There were no procedure-related complications. During mean follow-up of 9 months, 1 patient developed recurrent bleeding that was managed conservatively., Comments: Endovascular embolization is a safe alternative to open surgical intervention after failed endoscopic treatment for UGIB. Surgeons with endovascular skills can perform this procedure with superior results.