Factors Associated With Early Amputation in Patients With Chronic Limb Threatening Ischemia.

INTRODUCTION: Despite advancements in revascularization procedures, early amputation (EA) among patients with chronic limb threatening ischemia (CLTI) are still common. The present study evaluated clinical outcomes of patients with CLTI and factors associated with EA. METHODS: The 2016-2019 Nationwide Readmission Database was queried to identify all adults (≥18 years) with CLTI of lower extremities undergoing limb salvage (LS) procedures. The primary outcome of the study was EA within 90 days of discharge. Secondary outcomes included infectious complication, length of stay (LOS), cumulative hospitalization cost and non-home discharge. RESULTS: Of 103,703 patients who initially underwent surgical or endovascular revascularization, 10,439 (10.1%) subsequently underwent major amputation within 90 days of discharge. Following risk adjustment, factors associated with higher odds of EA were male sex, low-income quartile, tissue loss due to ulceration or gangrene, end-stage renal disease, and diabetes. Compared to those undergoing open revascularization, patients with endovascular limb salvage had a higher likelihood of having early amputation (AOR 1.41, 95% CI 1.31-1.51). Patients undergoing EA had greater odd of infectious complication, incremental LOS, incremental cost and non-home discharge. CONCLUSIONS: We identified several risk factors to be associated with EA in patients with CLTI. These findings may supplement the objective performance goals for limb-related outcomes and facilitate institutional limb salvage programs.

Association between Participation in a Preclinical Surgery Elective and Future Match into Surgical Residency.

BACKGROUND: Since 2013, we have offered a robust "Introduction to Surgery" elective (ITS) for preclinical medical students. The present study investigates whether participants of the ITS elective were more likely to match into surgical residencies than non-ITS participants. METHODS: This is a retrospective case-control study of medical students from two medical schools in Southern California who participated in the ITS elective and those who did not. Descriptive results and univariate analysis using STATA were utilized to analyze the de-identified data who matched between 2016 and 2021 were included. RESULTS: Overall, 87 (8.9%) of the 982 matched students participated in the ITS elective, with an increase in participation from 1.2% in 2016 to 13.9% in 2021 (P < .001). Among ITS participants, 49.4% matched into a surgical specialty compared to only 22.9% for non-ITS students (P < .001). There was no difference between ITS and non-ITS students with regards to procedural specialty match (14.9% vs 12.6%, P = .537). CONCLUSION: ITS participants were more than twice as likely to match into a surgical specialty than non-participants. Future qualitative research will help discern the relative impact of the ITS course versus a student's baseline predisposition to surgery.

Racial disparities in surgical management and outcomes of acute limb ischemia in the United States.

BACKGROUND: Although significant racial disparities in the surgical management of lower extremity critical limb threatening ischemia have been previously reported, data on disparities in lower extremity acute limb ischemia are lacking. METHODS: The 2012-2018 National Inpatient Sample was queried for all adult hospitalizations for acute limb ischemia (N = 225,180). Hospital-specific observed-to-expected rates of major lower extremity amputation were tabulated. Multivariable logistic and linear models were developed to assess the impact of race on amputation and revascularization. RESULTS: Nonwhite race was associated with significantly increased odds of overall (adjusted odds ratio: 1.16, 95% confidence interval 1.06-1.28) and primary (adjusted odds ratio: 1.34, 95% confidence interval 1.17-1.53) major amputation, decreased odds of revascularization (adjusted odds ratio 0.79, 95% confidence interval 0.73-0.85), but decreased in-hospital mortality (adjusted odds ratio: 0.86, 95% confidence interval 0.74-0.99). The nonwhite group incurred increased adjusted index hospitalization costs (ß: +$4,810, 95% confidence interval 3,280-6,350), length of stay (ß: + 1.09 days, 95% confidence interval 0.70-1.48), and nonhome discharge (adjusted odds ratio: 1.15, 95% confidence interval 1.06-1.26). CONCLUSION: Significant racial disparities exist in the management of and outcomes of lower extremity acute limb ischemia despite correction for variations in hospital amputation practices and other relevant hospital and patient characteristics. Whether the etiology lies primarily in patient, institution, or healthcare provider-specific factors has not yet been determined. Further studies of race-based disparities in management and outcomes of acute limb ischemia are warranted to provide effective and equitable care to all.

Contemporary outcomes of traumatic popliteal artery injury repair from the popliteal scoring assessment for vascular extremity injury in trauma study.

OBJECTIVE: Traumatic popliteal artery injuries are associated with the greatest risk of limb loss of all peripheral vascular injuries, with amputation rates of 10% to 15%. The purpose of the present study was to examine the outcomes of patients who had undergone operative repair for traumatic popliteal arterial injuries and identify the factors independently associated with limb loss. METHODS: A multi-institutional retrospective review of all patients with traumatic popliteal artery injuries from 2007 to 2018 was performed. All the patients who had undergone operative repair of popliteal arterial injuries were included in the present analysis. The patients who had required a major lower extremity amputation (transtibial or transfemoral) were compared with those with successful limb salvage at the last follow-up. The significant predictors (P < .05) for amputation on univariate analysis were included in a multivariable analysis. RESULTS: A total of 302 patients from 11 institutions were included in the present analysis. The median age was 32 years (interquartile range, 21-40 years), and 79% were men. The median follow-up was 72 days (interquartile range, 20-366 days). The overall major amputation rate was 13%. Primary repair had been performed in 17% of patients, patch repair in 2%, and interposition or bypass in 81%. One patient had undergone endovascular repair with stenting. The overall 1-year primary patency was 89%. Of the patients who had lost primary patency, 46% ultimately required major amputation. Early loss (within 30 days postoperatively) of primary patency was five times more frequent for the patients who had subsequently required amputation. On multivariate regression, the significant perioperative factors independently associated with major amputation included the initial POPSAVEIT (popliteal scoring assessment for vascular extremity injury in trauma) score, loss of primary patency, absence of detectable immediate postoperative pedal Doppler signals, and lack of postoperative antiplatelet therapy. Concomitant popliteal vein injury, popliteal injury location (P1, P2, P3), injury severity score, and tibial vs popliteal distal bypass target were not independently associated with amputation. CONCLUSIONS: Traumatic popliteal artery injuries are associated with a significant rate of major amputation. The preoperative POPSAVEIT score remained independently associated with amputation after including the perioperative factors. The lack of postoperative pedal Doppler signals and loss of primary patency were highly associated with major amputation. The use of postoperative antiplatelet therapy was inversely associated with amputation, perhaps indicating a protective effect.

Popliteal scoring assessment for vascular extremity injuries in trauma study.

OBJECTIVE: Traumatic popliteal vascular injuries are associated with the highest risk of limb loss of all peripheral vascular injuries. A method to evaluate the predictors of amputation is needed because previous scores could not be validated. In the present study, we aimed to provide a simplified scoring system (POPSAVEIT [popliteal scoring assessment for vascular extremity injuries in trauma]) that could be used preoperatively to risk stratify patients with traumatic popliteal vascular injuries for amputation. METHODS: A review of patients sustaining traumatic popliteal artery injuries was performed. Patients requiring amputation were compared with those with limb salvage at the last follow-up. Of these patients, 80% were randomly assigned to a training group for score generation and 20% to a testing group for validation. Significant predictors of amputation (P < .1) on univariate analysis were included in a multivariable analysis. Those with P < .05 on multivariable analysis were assigned points according to the relative value of their odds ratios (ORs). Receiver operating characteristic curves were generated to determine low- vs high-risk scores. An area under the curve of >0.65 was considered adequate for validation. RESULTS: A total of 355 patients were included, with an overall amputation rate of 16%. On multivariate regression analysis, the risk factors independently associated with amputation in the final model were as follows: systolic blood pressure <90 mm Hg (OR, 3.2; P = .027; 1 point), associated orthopedic injury (OR, 4.9; P = .014; 2 points), and a lack of preoperative pedal Doppler signals (OR, 5.5; P = .002; 2 points [or 1 point for a lack of palpable pedal pulses if Doppler signal data were unavailable]). A score of ≥3 was found to maximize the sensitivity (85%) and specificity (49%) for a high risk of amputation. The receiver operating characteristic curve for the validation group had an area under the curve of 0.750, meeting the threshold for score validation. CONCLUSIONS: The POPSAVEIT score provides a simple and practical method to effectively stratify patients preoperatively into low- and high-risk major amputation categories.

A Randomized Prospective Blinded Study Evaluating the Effect of Music on Novice Surgical Trainees' Ability to Perform a Simulated Surgical Task.

OBJECTIVE: To determine if playing music would affect novice surgical trainees' ability to perform a complex surgical task. BACKGROUND: The effect of music in the operating room (OR) is controversial. Some studies from the anesthesiology literature suggest that OR music is distracting and should be banned. Other nonblinded studies have indicated that music improves surgeons' efficiency with simple tasks. DESIGN/METHODS: A prospective, blinded, randomized trial of 19 novice surgical trainees was conducted using an in vitro model. Each trainee performed a baseline vascular anastomosis (VA) without music. Subsequently, they performed one VA with music (song validated to reduce anxiety) and one without, in random order and without prior knowledge of the study's purpose. The primary endpoint was a difference in differences from baseline with and without music with respect to time to completion, acceleration/deceleration (using a previously validated hand-tracking motion device), and video performance scoring (3 blinded experts using a validated scale). The participants completed a poststudy survey to gauge their opinions regarding music during tasks. RESULTS: Overall, 57 VAs by 19 trainees were evaluated. Average time to completion was 11.6 minutes. When compared to baseline, time to completion improved for both the music group (p = 0.01) and no-music group (p = 0.001). When comparing music to no music, there was no difference in time to completion (p = 0.7), acceleration/deceleration (p = 0.3), or video performance scorings (p = NS). Among participants, 89% responded that they enjoy listening to music while performing tasks. CONCLUSIONS: Using three outcome measures, relaxing music did not improve the performance of novice surgical trainees performing a complex surgical task, and the music did not make their performance worse. However, nearly all trainees reported enjoying listening to music while performing tasks.

Outcomes of Local and Regional Anesthesia for Superficialization of Brachiobasilic Arteriovenous Fistulas.

BACKGROUND: Superficialization, the second stage of a two-stage brachiobasilic arteriovenous fistula (BB-AVF), can be performed under local (LA), regional (RA), or general anesthesia (GA). Given the numerous comorbidities in patients with end-stage renal disease (ESRD), our preference is to use RA or LA when feasible. Our goal was to review the success rate of RA and LA, need for conversion to GA, and cardiac morbidity and mortality for BB-AVF superficialization. METHODS: We performed a retrospective cohort analysis of patients who underwent BB-AVF creation with second-stage superficialization over a 4-year period. The primary outcome measures included need for conversion to GA, myocardial infarction (MI), and 30-day mortality. A secondary outcome was total operative time (time from preoperative briefing to the time the patient left the operating room). We analyzed the data using Fisher Exact test for categorical data and nonparametric analysis for continuous data. RESULTS: There were 42 patients who underwent BB-AVF superficialization. The median age was 56 years, with a mean body mass index of 29. Most patients were male (55%) and predominantly Hispanic/Latino (60%). RA was utilized in 35 patients (83%), LA in 5 (12%), and GA in 2 (5%). The conversion rate from RA to GA was 0% and was 20% (n = 1) from LA to GA. There were no postoperative MI or deaths. There was no significant difference in total operative time (219.6 min for RA, 234.5 min for LA, and 278 min for GA, (P = 0.37)). CONCLUSIONS: Local and/or regional anesthesia can be successfully used in the majority of patients undergoing BB-AVF superficialization. LA and RA are associated with negligible cardiac morbidity and mortality. Conversion from RA to GA is rare. Use of RA does not result in a longer total operative time.

Racial Disparities in Limb Amputations After Traumatic Vascular Injury.

OBJECTIVES: The influence of race or ethnicity on limb loss after traumatic vascular injury is unclear. We sought to determine whether there were racial differences in rates of amputation between American Indians, blacks, Asians, and Hispanics compared to white patients following arterial axillosubclavian vessel injury (ASVI), femoral artery injury (FAI), or popliteal artery injury (PAI). As black race has been identified as an independent prognostic factor for postsurgical complication in trauma-associated lower extremity amputation, we further hypothesized that black race would be associated with a higher risk for limb loss after arterial ASVI, FAI, and PAI injury in a large national database. METHODS: The National Trauma Data Bank was queried for patients ≥16-years-old with arterial ASVI, FAI, or PAI to determine the risk of arm, above knee amputation (AKA), and below knee amputation (BKA), respectively. Covariates were included in separate multivariable logistic regression models for analysis. The reference group included white trauma patients. RESULTS: From 5,683,057 patients, 21,843 were identified with arterial ASVI, FAI, or PAI (<0.4%). For arterial ASVI, American Indian race was associated with higher risk for upper-extremity amputation as compared to white race (OR = 5.10, CI = 1.62-16.06, p < 0.05). For FAI, black race was associated with (OR = 0.66, CI = 0.49-0.89, p < 0.05) a lower risk of AKA, compared to white race. For PAI, race was not associated with risk for BKA. CONCLUSION: Black race is associated with a lower risk of AKA after FAI, compared to whites. Race was not associated with a risk for limb loss after PAI. Future prospective studies examining socioeconomic factors and access to healthcare within this patient population is warranted to identify barriers and areas of improvement.

Careful Patient Selection Achieves High Radiocephalic Arteriovenous Fistula Patency in Diabetic and Female Patients.

BACKGROUND: The radiocephalic arteriovenous fistula (rcAVF) is considered the first-choice site for hemodialysis access; however, it has been associated with decreased rates of patency and maturation in women and diabetic patients in some studies. We hypothesized that careful preoperative selection of patients for an rcAVF fistula would result in a high 1-year patency rate and that external factors, such as female gender and diabetes mellitus (DM), would not adversely affect fistula patency. METHODS: This is a retrospective study of all patients who underwent rcAVF creation at a single institution from January 2011 to June 2016. Patients were carefully selected based on clinical examination and preoperative, B-mode, ultrasound findings. Primary patency and primary assisted patency at 1 year were calculated. Survival analysis was also conducted to evaluate for factors associated with rcAVF patency. RESULTS: There were 158 patients identified who underwent rcAVF fistula creation and were seen in follow-up. The 1-year primary and primary assisted patency rates were 62% and 81%, respectively. On Kaplan-Meier survival analysis, there was no difference in rcAVF patency with respect to gender, Hispanic race, anesthesia type, DM, and smoking status. Patients with a prior AVF, most often received in the nondominant arm and now receiving an rcAVF in the dominant arm, had a significantly higher risk of fistula failure, in both primary and primary assisted patency survival (hazard ratio 5.1, 95% confidence interval 1.6-16.2, P = 0.06). Patients without a history of hypertension (HTN), as noted in the electronic medical records, trended toward a higher risk of primary assisted patency rcAVF failure, compared to those who had a history of HTN (hazard ratio 3.0, 95% confidence interval 1.1-7.9, P = 0.03). CONCLUSIONS: With careful patient selection, the rcAVF can achieve a high 1-year primary assisted patency rate. Female gender and DM were not significantly associated with an increase in rcAVF failure and should not be heavily relied on in-patient selection. First-time AVF patients and patients with a history of HTN may be associated with increased rcAVF patency.

Preoperative Antibiotics for Dialysis Access Surgery: Are They Necessary?

BACKGROUND: Current guidelines recommend preoperative antibiotics in all vascular surgery cases. However, we hypothesize that patients undergoing arteriovenous fistula (AVF) and arteriovenous graft (AVG) creation have low rates of postoperative surgical site infection (SSI) and that preoperative antibiotic prophylaxis in these patients may not be necessary. METHODS: This is a retrospective review of all patients who underwent AVF and AVG creation from November 2014 through July of 2016 at a single institution. At our institution, preoperative antibiotic use is surgeon dependent. Patients who received preoperative antibiotics were compared with those who did not. The primary outcome measured was the development of postoperative SSI. RESULTS: There were 304 patients identified and 294 patients with 30 day postoperative follow-up. Of the 294 patients, 23 (7.8%) received an AVG, and 271 (92.2%) received an AVF. There were 244 (83%) patients who received preoperative antibiotics and 50 (17%) who did not. Overall, there were 2 (0.68%) SSIs identified. Both patients with postoperative SSI underwent AVF creation and received preoperative antibiotics. There was no statistically significant difference in SSI rate between antibiotic and nonantibiotic groups (P = 1.0), and no difference when comparing patients that received AVG (0%) and AVF (0.73%) (P = 1.0). CONCLUSIONS: The rate for postoperative SSI following hemodialysis access surgery is very low both for patients undergoing AVF and AVG. Furthermore, there was no difference in SSI rate between antibiotic and nonantibiotic groups. Given these findings, we conclude that preoperative antibiotics for AVF creation may not be necessary.

Factors Associated with Early Thrombosis after Arteriovenous Fistula Creation.

BACKGROUND: Arteriovenous fistulas (AVF) are the preferred modality for hemodialysis access. Early thrombosis hampers development of a working AVF. We endeavored to determine the incidence and identify factors associated with early thrombosis of AVF and to determine salvage rates following thrombosis, at a high-volume hemodialysis access center. METHODS: Retrospective review of autologous AVF was created between November 2014 and July 2016 at a single center. Early thrombosis was defined as thrombosis that occurred within 30 days of surgery. RESULTS: There were 291 AVFs. The median age was 54.7 years, and 192 patients (66%) were male. Early postoperative AVF thrombosis was noted in 5 (1.7%) cases. Factors associated with early thrombosis on univariate analysis included previous access surgery (P = 0.02) and absence of a good intraoperative thrill (P = 0.006). Intraoperative protamine use trended toward significance (P = 0.06). Factors that were not significant included gender, diabetes, dialysis at time of surgery, fistula configuration, and systemic heparin use. None of the thrombosed fistulas were salvaged. CONCLUSIONS: Early thrombosis is a relatively rare complication of AVF creation at a high-volume center. Previous access surgery and absence of good thrill at conclusion of the procedure are associated with early thrombosis.

Ultrasound Vein and Artery Mapping by General Surgery Residents During Initial Consult Can Decrease Time to Dialysis Access Creation.

BACKGROUND: Formal preoperative ultrasound (US) mapping of vascular anatomy by radiology is recommended before hemodialysis access surgery. We hypothesized that US performed by general surgery residents in place of formal US would decrease the time from initial consult to creation of dialysis access without affecting patient outcomes. METHODS: This is a retrospective review of all patients who underwent dialysis access surgery from November 2014 to July 2016 and received preoperative upper extremity US vein and artery evaluation by either radiology or general surgery residents. The primary endpoints were days from initial consult to dialysis access creation, rate of arteriovenous fistula (AVF) creation, fistula maturation, and 1-year primary assisted patency. RESULTS: Of 242 patients, 167 (69%) had formal US, and 75 (31%) had only a resident US. The resident US group had 100% AVF creation compared with the formal US group with 92.2% AVF creation (P = 0.01). There was no difference between the groups in rate of fistula maturation (P = 0.1) and 1-year assisted patency (P = 0.9). Of the resident US 90.7% occurred in the outpatient setting. On multivariable analysis controlling for outpatient consult, the average time to the operating room was 13.7 days longer for the formal US group in the outpatient setting (P = 0.0006). CONCLUSIONS: Ultrasound vein and artery evaluation at the time of the initial consult by general surgery residents can decrease the time to dialysis access creation by bypassing the need for formal US with a higher rate of AVF creation and no difference in fistula maturation or 1-year primary assisted patency.

A Comparative Analysis of Open versus Endovascular Techniques for Management of Non-Aortic Cervicothoracic Arterial Injuries.

The objective of this study is to describe the contemporary management of proximal upper extremity and neck arterial injuries by comparing open and endovascular repair at a single institution. This is a retrospective study of 22 patients that sustained subclavian, axillary, and carotid artery injuries from 2011 to 2016 that were managed with open or endovascular repair. There were nine subclavian, eight axillary, and five carotid artery injuries of which 10 (45.5%) underwent endovascular repair and 12 (54.5%) underwent open repair. There was no statistically significant difference between the groups including injury severity score or preoperative hypotension. There were no deaths in the endovascular group, and three (25.0%) deaths in the open group. All patients in the endovascular group were discharged home. In the open group, seven (58.3%) patients had at least one inpatient complication with a mean of 1.1 (standard deviation 1.4) complications per patient. In the endovascular group, there were three (30.0%) patients with inpatient complications and a mean of 0.4 (standard deviation 0.7) complications per patient (P = 0.18). Endovascular management of nonaortic cervicothoracic arterial injuries was successfully performed in hypotensive patients and patients with other life threatening traumatic injuries. Further studies are warranted to look at long-term patency of these repairs and to help develop a protocol to guide decision-making in the management of cervicothoracic injuries.

The Burden of Tunneled Central Venous Catheters for Hemodialysis in a County Hospital.

Prolonged use of central venous catheters (CVCs) for hemodialysis (HD) is associated with greater morbidity and mortality when compared with autogenous arteriovenous fistulas (AVF). The objective was to assess compliance with CVC guidelines in adults referred for hemoaccess at a county teaching hospital. Out of 256 patients, 172 (67.2%) were male, with a mean age of 50.0 ± 12.4 years. Overall 62.5 per cent initiated dialysis via CVC. Patients were divided into two groups (those with CVC (62.5%) and those without (37.5%)). Male gender was associated with initiation of dialysis via CVC versus no CVC (72.5 vs 58.3%, P = 0.02), as was a history of prior vascular access (P < 0.01). There were no significant differences between the groups regarding age, diabetes, smoking, ambulatory status, or insurance status. There were no differences in gender, age, insurance status, or prior vascular access between prolonged CVC use (≥90 days) and short-term CVC use (<90 days). We conclude that most patients initiated HD with CVC and exceed the recommended CVC duration. Men are more likely to initiate HD via CVC. Insurance status was not associated with CVC use. Multidisciplinary action may address barriers to reducing CVC duration.

Predictors of Steal in Hemodialysis Access.

Pathological steal is an uncommon but devastating complication after the creation of arteriovenous access for hemodialysis. In this study, we sought to assess predictors of clinically significant steal syndrome and to further evaluate the outcome of differing surgical treatment approaches. A retrospective analysis was performed of 282 consecutive patients undergoing hemodialysis access at a single center from November 2014 to April 2016. Adequate follow-up to assess for the development of steal was obtained in 237 patients. One hundred and fifty-seven (66%) patients were male, 152 (64%) Hispanic, and 164 (69%) had diabetes. Forty-three (18%) had prior access procedures. Autologous fistula was created in 218 patients (92%). Pathologic steal occurred in 15 patients (6.7%). On univariate analysis, significant predictors of steal included female sex [P = 0.03, odds ratio (OR) = 3.3, CI [1.1-9]), no systemic heparin at operation (P = 0.02, OR = 5.0, CI [1.4-10]), use of angiotensin-converting enzyme inhibitor (P = 0.003, OR = 5.6, CI [1.7-18.6]), and increased vein size (3.1 vs 4.1 mm P = 0.01). Twelve patients had steal managed with an intervention, but only one patient received distal revascularization. Furthermore, we identify key predictors of clinically significant steal syndrome while demonstrating that distal revascularization and/or fistula ligation are rarely indicated treatment modalities.

The virtual-patient pilot: testing a new tool for undergraduate surgical education and assessment.

BACKGROUND: The virtual patient (VP) is a web-based tool that allows students to test their clinical decision-making skills using simulated patients. METHODS: Three VP cases were developed using commercially available software to simulate common surgical scenarios. Surgical clerks volunteered to complete VP cases. Upon case completion, an individual performance score (IPS, 0-100) was generated and a 16-item survey was administered. Surgery shelf exam scores of clerks who completed VP cases were compared with a cohort of students who did not have exposure to VP cases. Descriptive statistics were performed to characterize survey results and mean IPS. RESULTS: Surgical clerks felt that the VP platform was simple to use, and both the content and images were well presented. They also felt that VPs enhanced learning and were helpful in understanding surgical concepts. Mean IPS at conclusion of the surgery clerkship was 69.2 (SD 26.5). Mean performance on the surgery shelf exam for the student cohort who had exposure to VPs was 86.5 (SD 7.4), whereas mean performance for the unexposed student cohort was 83.5 (SD 9). DISCUSSION: The VP platform represents a new educational tool that allows surgical clerks to direct case progression and receive feedback regarding clinical-management decisions. Its use as an assessment tool will require further validation.

Myocardin regulates BMP10 expression and is required for heart development.

Myocardin is a muscle lineage-restricted transcriptional coactivator that has been shown to transduce extracellular signals to the nucleus required for SMC differentiation. We now report the discovery of a myocardin/BMP10 (where BMP10 indicates bone morphogenetic protein 10) signaling pathway required for cardiac growth, chamber maturation, and embryonic survival. Myocardin-null (Myocd) embryos and embryos harboring a cardiomyocyte-restricted mutation in the Myocd gene exhibited myocardial hypoplasia, defective atrial and ventricular chamber maturation, heart failure, and embryonic lethality. Cardiac hypoplasia was caused by decreased cardiomyocyte proliferation accompanied by a dramatic increase in programmed cell death. Defective chamber maturation and the block in cardiomyocyte proliferation were caused in part by a block in BMP10 signaling. Myocardin transactivated the Bmp10 gene via binding of a serum response factor-myocardin protein complex to a nonconsensus CArG element in the Bmp10 promoter. Expression of p57kip2, a BMP10-regulated cyclin-dependent kinase inhibitor, was induced in Myocd-/- hearts, while BMP10-activated cardiogenic transcription factors, including NKX2.5 and MEF2c, were repressed. Remarkably, when embryonic Myocd-/- hearts were cultured ex vivo in BMP10-conditioned medium, the defects in cardiomyocyte proliferation and p57kip2 expression were rescued. Taken together, these data identify a heretofore undescribed myocardin/BMP10 signaling pathway that regulates cardiomyocyte proliferation and apoptosis in the embryonic heart.

Myocardin-like protein 2 regulates TGFß signaling in embryonic stem cells and the developing vasculature.

The molecular mechanisms that regulate and coordinate signaling between the extracellular matrix (ECM) and cells contributing to the developing vasculature are complex and poorly understood. Myocardin-like protein 2 (MKL2) is a transcriptional co-activator that in response to RhoA and cytoskeletal actin signals physically associates with serum response factor (SRF), activating a subset of SRF-regulated genes. We now report the discovery of a previously undescribed MKL2/TGFß signaling pathway in embryonic stem (ES) cells that is required for maturation and stabilization of the embryonic vasculature. Mkl2(-/-) null embryos exhibit profound derangements in the tunica media of select arteries and arterial beds, which leads to aneurysmal dilation, dissection and hemorrhage. Remarkably, TGFß expression, TGFß signaling and TGFß-regulated genes encoding ECM are downregulated in Mkl2(-/-) ES cells and the vasculature of Mkl2(-/-) embryos. The gene encoding TGFß2, the predominant TGFß isoform expressed in vascular smooth muscle cells and embryonic vasculature, is activated directly via binding of an MKL2/SRF protein complex to a conserved CArG box in the TGFß2 promoter. Moreover, Mkl2(-/-) ES cells exhibit derangements in cytoskeletal organization, cell adhesion and expression of ECM that are rescued by forced expression of TGFß2. Taken together, these data demonstrate that MKL2 regulates a conserved TGF-ß signaling pathway that is required for angiogenesis and ultimately embryonic survival.

Reno-hepatic artery bypass for an inferior pancreaticoduodenal artery aneurysm with associated celiac occlusion.

Pancreaticoduodenal artery (PDA) aneurysms are rare and often found in association with lesions of the celiac axis. We report the case of a 72-year-old morbidly obese male who presented with chronic abdominal pain and a 4.5 cm inferior PDA aneurysm with associated occlusion of the celiac axis. The patient was treated successfully with right renal to common hepatic artery bypass followed by aneurysm ligation and excision. When encountered, PDA aneurysms require expeditious treatment. Precise definition of vascular anatomy and collateral flow is mandatory. While endovascular techniques may aid in management, surgery remains the most effective treatment for complex aneurysms of the pancreaticoduodenal arteries.

Carotid artery stenting: clinical trials and registry data.

Despite the lack of Level I evidence, carotid artery stenting (CAS) has emerged as an alternative to carotid endarterectomy (CEA). Furthermore, CAS has been met with considerable enthusiasm due to its minimally invasive nature and potential application to high-risk patient populations. Several investigations including multicenter registries and randomized controlled trials have been established and are currently underway in an effort to evaluate the noninferiority and efficacy of CAS as compared to CEA. To date, no trial has definitively shown equivalence of CAS to CEA for the treatment of carotid stenosis and consensus recommendations for use of CAS remain very restricted. Nevertheless, the existing data have provided useful information with respect to differential outcomes in subgroups, including symptom status, age, gender, and high-risk patient populations. Until the noninferiority of CAS is clearly demonstrated in a randomized controlled setting, CEA remains the gold standard for treatment of carotid stenosis and use of CAS must be carefully considered on an individual patient basis.