Ethnicity-based differences in thrombosis in lower extremity vascular bypass: a review of current literature.

INTRODUCTION: Understanding prothrombotic factors is important in vascular surgery for surgical planning, preoperative evaluation, and post-operative management. The purpose of this study was to investigate ethnicity-based differences in coagulation between East Asian and Western cohorts by comparing patency rates after infrainguinal bypass surgery. EVIDENCE ACQUISITION: A review of infrainguinal bypass patients was conducted for East Asian (including Chinese, Japanese, and Korean) and Western (North American and European) studies between 1990 and 2015 within the Journal of Vascular Surgery. The number of patent grafts at 1-year and 5-years were calculated from reported patency rates for PTFE grafts, Dacron grafts, all prosthetic grafts, autogenous grafts, and all grafts. Statistical analysis was performed using Chi-square test for each graft type at each time point. EVIDENCE SYNTHESIS: A total of 9972 grafts from 50 studies were included in our review. There were 3592 grafts from East Asian patients and 6380 grafts from Western patients. There was a statistically significant (P<0.05) difference between East Asian and Western cohorts in both 1-year and 5-year patency rates for PTFE, all prosthetic, and all grafts. CONCLUSIONS: East Asians had significantly higher patency rates after infrainguinal bypass surgery for PTFE, all prosthetic, and all graft types compared with Westerners, showing an ethnicity-based difference in thrombosis. Further research is needed to identify the specific genetic or dietary influences causing this significant difference.

Changes in Hospital Discharges with Alcohol-Related Liver Disease in a Gastroenterology and General Medical Unit Following the Introduction of Minimum Unit Pricing of Alcohol: The GRI Q4 Study.

AIMS: Minimum unit price (MUP) of 50 pence per unit of alcohol was introduced in Scotland on the 1 May 2018. We assessed alcohol-related liver disease (ArLD) discharges from Glasgow Royal Infirmary (GRI) before and after the introduction of MUP. METHODS: Medical records of all patients discharged from Gastroenterology wards at GRI in the fourth quarter (Q4) of the years 2015-2019 were reviewed. All patients with ArLD were identified, and detailed hospitalization data were collected retrospectively. Active drinking, severity scores, presence of alcoholic hepatitis (AH) and 90-day mortality and readmission rates were assessed. RESULTS: There were fewer ArLD discharges per quarter after MUP than before (mean 80.3 pre-MUP; mean 68 post-MUP), and the proportion of active drinkers was lower post-MUP (64.7 vs. 70.5%). There was a significant fall in the mean number of weekly discharges of individual patients who were actively drinking (4.0 ± 2.0 pre-MUP, 2.8 ± 1.5 post-MUP, P = 0.01). There were no differences in the proportion of patients presenting with ascites, encephalopathy or AH; however, there was a reduction in presentations with acute upper gastrointestinal bleeding from 15.8% pre-MUP to 7.4% post-MUP (P = 0.02; odds ratio 0.42). Severity of liver disease remained unchanged. The 90-day mortality and readmission rates were not significantly different. CONCLUSION: Since the introduction of MUP there has been a reduction in the absolute numbers of patients discharged with ArLD and the number of individual patients involved at GRI. The pattern of clinical presentation was largely unaffected with overall ArLD severity, readmission rates and 90-day mortality similar pre- and post-MUP.

Distal perfusion cannulae reduce extracorporeal membrane oxygenation-related limb ischemia.

BACKGROUND: Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is a means of providing cardiopulmonary support that is being increasingly used in patients with acute heart failure. When ECMO cannulae are placed peripherally, their large diameters pose a risk of limb ischemia. Distal perfusion cannulae (DPC) have been proposed as means to reduce risk, but their use is not recommended by the most recent ECMO guidelines. We sought to establish their utility at our institution. METHODS: We performed a retrospective review of of all patients treated with peripheral VA-ECMO at our institution from 2013-2018. During the first 2 years, DPC were not routinely placed, whereas in the final 4 years, DPC were recommended as part of the ECMO cannulation routine. RESULTS: One hundred and one patients were treated with peripheral VA-ECMO, with an overall mortality of 61%. By univariate analysis, obesity (47% vs. 75%, P<0.01) and limb ischemia (57% vs. 83%, P<0.05) were associated with increased mortality. DPC were placed prophylactically in 49% of patients. Prophylactic placement of a DPC at the time of cannulation significantly reduced the incidence of limb ischemia (2% vs. 32%, P<0.05), but did not impact mortality (53% vs. 69%, P=0.0953). In patients who did not have a DPC placed during ECMO cannulation and subsequently developed limb ischemia, late DPC placement for limb salvage did not impact mortality. CONCLUSIONS: Limb ischemia portends a poor outcome in VA-ECMO patients, and prophylactic DPC placement significantly reduces the risk of limb ischemia. We propose prophylactic DPC placement be considered in patients requiring peripheral VA-ECMO.

Lessons learned during a 30-year experience with simultaneous carotid endarterectomy and coronary artery bypass grafting.

OBJECTIVE: A simultaneous operative approach to patients with significant carotid and coronary disease has been suggested as a safe, lower cost, and more convenient alternative to a staged approach. During the last three decades, spanning the career of our senior author, our group has pursued simultaneous coronary artery bypass grafting (CABG) and carotid endarterectomy (CEA) in limited circumstances. We previously reported on our results in series from 1984 to 1994 and 1994 to 1999. Based on these prior results and the current literature, we liberalized our inclusion criteria. We are now reporting on a contemporary cohort of 91 patients operated on from 2006 to 2018. METHODS: All patients who underwent combined CEA/CABG in 2006 to 2018 were entered into the Vascular Quality Initiative database. We compared the current series of 91 patients (group 3) with the 74 patients (group 2) from 1994 to 1999 and the 100 patients (group 1) from 1984 to 1994 who also underwent combined CEA/CABG. We examined demographic and comorbid factors, presence of cerebrovascular symptoms, degree of contralateral carotid stenosis, perioperative stroke, and death. Statistical comparison was made with χ2 analysis. RESULTS: The groups had similar demographics and comorbidities. Significant differences were noted in the preoperative diagnosis of hyperlipidemia (42%, 51%, 75%; P = .005) and the proportion of patients requiring urgent operations (24%, 47%, 56%; P = .002) during successive time periods. Patients in group 3 were much less likely to have preoperative symptoms from carotid stenosis before operation (55%, 31%, 4.4%; P < .001). Correspondingly, patients in group 3 were more likely to have asymptomatic unilateral carotid stenosis (20%, 55%, 78%; P < .001). The 30-day mortality rate remained stable compared with the first interval (8%, 3%, 2.2%; P = .11). Likewise, the overall stroke rate decreased in the later periods compared with the first series (9%, 1.4%, 2.2%; P = .016). Of the two perioperative strokes recorded for group 3, only one event was ipsilateral to the carotid artery operated on compared with the four ipsilateral strokes of nine total reported in group 1 and no ipsilateral stroke reported in group 2. CONCLUSIONS: Based on the favorable results of the previously reported series of CEA/CABG from our group, we continued to liberalize selection criteria for the combined procedure to essentially mirror the standard recommendations for CEA in patients without coronary disease. The current series using this treatment algorithm demonstrates the safety of this approach, with stroke and death rates equivalent to those of CABG alone. These excellent results were achieved in the face of increasingly urgent cardiac procedures. The fact that the majority of the perioperative strokes were contralateral to the carotid artery operated on reinforces the safety of our approach but underscores the significant burden of atherosclerosis in these patients.

Race-based disparities in presentation and outcomes in infrainguinal bypass patients.

BACKGROUND: Racial disparities in healthcare are well documented, however their effects on surgical outcomes remain controversial. While studies have examined outcomes along the white-black dichotomy, Asian populations remain frequently unstudied. We use the VQI to examine disparities among white, black and Asian patients undergoing infrainguinal bypass. METHODS: The VQI database was queried for black, white and Asian patients undergoing infrainguinal surgery between 2012 and 2017. Preoperative characteristics, disease severity, and perioperative characteristics were compared between the racial groups. Primary outcomes included overall mortality, time to death, long term loss of primary patency, and patency at discharge. Analyses were done using a 1:3:3 matched sample of Asian to whites to black patients. RESULTS: Among the patients included, 139 (0.56%) were Asian, 4222 (16.9%) were black and 20,582 (82.5%) were white, of which 129 Asian patients were matched to 387 black and 387 white patients. Asian patients had more advanced disease as demonstrated by higher rates of tissue loss/acute ischemia (P<0.0001) and the highest percentage of below knee popliteal target sites (P=0.0011). There were no differences in mortality (P=0.6808) or long-term loss of primary patency (P=0.4500). However, black patients had higher rates of amputation (OR=1.68, P=0.0224) and reoperation (OR=2.22, P=0.0015). CONCLUSIONS: Asian patients presented with more advanced disease requiring more distal bypass targets. Despite these disparities in presentation, overall long-term primary patency and mortality showed no significant difference.

A Review of the Efficacy and Safety Profiles of the Novel Oral Anticoagulants in the Treatment and Prevention of Venous Thromboembolism.

PURPOSE: This study aims to review the published literature concerning the use of novel oral anticoagulants (NOACs) in the treatment and prevention of venous thromboembolism (VTE) and to identify the appropriate niche for each NOAC by comparing their behaviors in Phase III and Phase IV clinical trial settings. METHODS: The ClinicalTrials.gov database was used to identify Phase III and postmarketing (Phase IV) randomized controlled trials concerning the efficacy and safety profiles of the oral NOACs (apixaban, dabigatran etexilate, exodaban, and rivaroxaban) for the treatment or prevention of VTE. Studies of special interest included those that compared the administration of a NOAC versus standard anticoagulation therapy with low-molecular-weight heparin and/or a vitamin K antagonist. FINDINGS: Overall, the NOACs offer a simplified anticoagulation regimen that has noninferiority and similar rates of bleeding when compared with standard therapy throughout multiple studies. This finding held true across several VTE conditions that required anticoagulation, such as the treatment and prophylaxis of acute VTE, including both deep vein thrombosis and pulmonary embolism. Absence of dietary restrictions and fixed oral dosing that does not require monitoring makes NOACs ideal for the outpatient setting. Apparent niches for each individual NOAC are discussed in detail; however, the paucity of trials comparing NOAC performance in specific clinical settings makes precise definition of these niches problematic. IMPLICATIONS: It now seems reasonable for clinicians to consider NOACs as first-line agents for both the treatment and prophylaxis of VTE and to attempt to tailor their particular medication choices for each patient scenario. More trials comparing NOAC performance in specific clinical settings are essential to ensure these medications are being used to their full potential.

Perioperative ß-Blockade in Noncardiac Surgery: A Cautionary Tale of Over-reliance on Small Randomized Prospective Trials.

PURPOSE: Our aim was to analyze the current scientific literature relevant to the use of ß-adrenergic receptor antagonists for the prevention of cardiovascular morbidity and mortality in patients undergoing noncardiac surgery. METHODS: A PubMed search was conducted for the following concepts: pre- or perioperative, ß-adrenergic receptor antagonist, treatment outcome, and cardiovascular complication. Randomized clinical trials measuring the effect of ß-adrenergic blocking agents against that of placebo on cardiovascular outcomes after noncardiac surgery were included in the review. FINDINGS: Two small randomized controlled trials published in 1996 and 1999 reported associations between perioperative ß-blockade and significant reductions in long-term and 30-day cardiac mortality, respectively. These 2 studies prompted guideline changes in 2002 encouraging perioperative ß-blockade in subsets of noncardiac surgery patients. However, subsequent trials failed to validate these results. In 2008, the first large randomized controlled trial on the topic was published and found an association between perioperative ß-blockade and an increase in perioperative mortality. Furthermore, in 2011, the lead author of the 1999 study was dismissed from his academic position for scientific misconduct, casting doubt on the validity of guidelines based on his work. Existing studies are highly heterogeneous, making comparisons difficult. Current literature does not support initiating perioperative ß-blockade in noncardiac surgery patients not already receiving these medications. IMPLICATIONS: Future research on the topic should account for the influence individual genetic variation can have on outcomes and ß-blocker metabolism. Additionally, the relationship between outcomes and the ß-1 selectivity of different ß-blockers should be explored.

Progression of moderate-to-severe carotid disease.

OBJECTIVE: Our goals were to investigate the degree to which patient demographics, risk factors, laboratory data, and medications influence moderate carotid disease progression among patients with asymptomatic moderate carotid disease and whether such associations are solely based on how progression is defined. In addition, we aimed to establish optimal threshold criteria to categorize patients at high risk of progression. METHODS: In this retrospective study, 621 arteries were evaluated for internal carotid artery (ICA) stenosis between January 1997 and January 2014 and were determined to have moderate (50%-79%) stenosis via color duplex ultrasonography. "Moderate stenosis" was defined as an ICA peak systolic velocity (PSV) ≥120 cm/s and a diastolic ICA velocity <140 cm/s. Kaplan-Meier analysis of the time to progression was conducted using three independent end points: PSV ≥230 cm/s (liberal criterion); ICA/common carotid artery (CCA) ratio ≥4.0 (moderate criterion), and diastolic ICA velocity ≥140 cm/s (strict criterion). Kaplan-Meier survival curves were generated, and multivariate analysis was performed using Cox regression models. Risk stratification criteria were based on optimal sensitivity and specificity generated from receiver operating characteristic (ROC) curve analysis. RESULTS: The overall rate of progression was 28.5%, 21.1%, or 5.1% of study-eligible arteries over 5 years using liberal, moderate, or strict criterion, respectively. Using liberal criterion, multivariate analysis suggested that initial PSV ≥200 cm/s, ICA/CCA ratio ≥3, and male gender were significantly associated with progression. Using the moderate criterion, multivariate analysis revealed that initial PSV ≥200 cm/s, ICA/CCA ratio ≥3, age, and male gender were significantly associated with progression. Using the strict criterion, multivariate analysis revealed that initial PSV ≥200 cm/s was the only statistically significant predictor of progression. No additional patient demographics, comorbidities, initial laboratory values, or medications consistently influenced disease progression across any criteria in our study. ROC analysis suggests PSV ≥165 cm/s is an ideal threshold value for the categorization of high risk patients, as this resulted in an optimal screening sensitivity of nearly 91% and a specificity of 59% over 2 years. CONCLUSIONS: The timing and incidence of carotid disease progression depends on the definition of disease progression. Among all three criteria, only severity of disease at initial presentation reliably predicted progression. Based on the results of our ROC curve analysis, we propose that an initial ICA PSV ≥165 cm/s (sensitivity: 90.7%, specificity: 58.7%) represents a reasonable value for defining high progression risk over a 2-year interval.

Risk factors for 30-day readmissions and modifying postoperative care after gastric bypass surgery.

BACKGROUND: Although hospital 30-day readmissions policies currently focus on medical conditions, readmission penalties will be expanding to encompass surgical procedures, logically beginning with common and standardized procedures, such as gastric bypass. Therefore, understanding predictors of readmission is essential in lowering readmission rate for these procedures. STUDY DESIGN: This is a retrospective case-control study of patients undergoing laparoscopic gastric bypass at Tufts Medical Center from 2007 to 2012. Variables analyzed included demographics, comorbidities, intraoperative events, postoperative complications, discharge disposition, and readmission diagnoses. Univariate analysis was used to identify factors associated with readmission, which were then subjected to multivariable logistic regression analysis. RESULTS: We reviewed 358 patients undergoing laparoscopic gastric bypass, 119 readmits, and 239 controls. By univariate analysis, public insurance, body mass index >60 kg/m(2), duration of procedure, high American Society of Anesthesiologists (ASA) class, and discharge with visiting nurse services (VNA) were significantly associated with 30-day readmissions. In the regression model, duration of procedure, high ASA class, and discharge with visiting nurse services (VNA) remained significantly associated with readmission when controlling for other factors (odds ratio [OR] 1.523, 95% CI 1.314 to 1.766; OR 2.447, 95% CI 1.305 to 4.487; and OR 0.053 with 95% CI 0.011 to 0.266, respectively). The majority of readmissions occurred within the first week after discharge. Gastrointestinal-related issues were the most common diagnoses on readmission, and included anastomotic leaks, postoperative ileus, and bowel obstruction. The next 2 most common reasons for readmission were wound infection and fluid depletion. CONCLUSIONS: Using readmission risk, we can stratify patients into tiered clinical pathways. Because most readmissions occur within the first postdischarge week and are most commonly associated with dehydration, pain, or wound issues, focusing our postoperative protocols and patient education should further lower the incidence of readmission.

Predictive risk factors for 30-day readmissions following primary total joint arthroplasty and modification of patient management.

The Centers for Medicare and Medicaid have begun to publically publish statistics on readmissions following primary total hip (THA) and total knee arthroplasty (TKA). Our study retrospectively assesses 30-day readmissions rates following THA and TKA, performed by a single surgeon at a tertiary care medical center between 2007 and 2012. Results of a univariate analysis and logistic regression model indicated female gender, high ASA class, and increased operative time to be significantly associated with higher rates of readmission (OR 4.646, OR 1.257, and OR 5.323, respectively). Readmissions most often occurred within the first week of patient discharge. Surgical complications and gastrointestinal discomfort were the most common causes for readmission. Using readmission risk we can stratify patients into tiered critical care pathways to reduce readmissions.

The limits of evidence in drug approval and availability: a case study of cilostazol and naftidrofuryl for the treatment of intermittent claudication.

PURPOSE: Despite numerous efforts to develop effective medications for the treatment of intermittent claudication (IC) over the past 4 decades, a gold standard medical management option has yet to be defined. Although not life-threatening, IC interferes with mobility and activities of daily living, significantly impairing quality of life and potentially causing depression. Cilostazol, the leading pharmacologic agent for IC in the United States, was approved by the US Food and Drug Administration (FDA) in 1999 based on controversial data. Meanwhile, naftidrofuryl, the first-line pharmacologic agent for IC in the United Kingdom and Europe, has never been approved by the FDA and therefore is not available in the United States. The clinical data for cilostazol and naftidrofuryl are plagued by flaws related to lack of protocol standardization, objective endpoints, and strict eligibility criteria in study subjects, making identification of a true treatment effect impossible. Furthermore, no prospective randomized trial comparing the efficacy of cilostazol and naftidrofuryl has been conducted, because the manufacturers of these agents have much to lose and little to gain from such a study. OBJECTIVE: This article provides an overview of the pharmacology of cilostazol and naftidrofuryl, and the clinical studies leading to their approval and clinical acceptance. It further explores the possible sources of bias in analyzing these clinical trials, some of which have been brought to light by the National Institute for Health and Clinical Excellence (NICE) of the United Kingdom in its technology appraisal guidance. It also speculates the ways in which economic incentives may affect drug-marketing decisions. METHODS: A literature review of pharmacology and clinical trials for cilostazol and naftidrofuryl was performed in PubMed. The majority of included clinical trials were initially identified through the most recent Cochrane review articles as well as the FDA's approval packet for cilostazol. The technology appraisal guidance of the National Institute for Health and Care Excellence of the United Kingdom and the manufacturer's response to this guidance document were located via an online search engine. FINDINGS: The clinical data for cilostazol and naftidrofuryl are plagued by flaws related to lack of protocol standardization, objective endpoints, and strict eligibility criteria in study subjects, making identification of a true treatment effect difficult. Furthermore, no prospective randomized trial comparing the efficacy of cilostazol and naftidrofuryl has been conducted. IMPLICATIONS: The history of the evaluation, approval, and marketing of these drugs illustrates the limitations of data in the regulatory approval and marketing of agents whose benefit is subjective and difficult to quantify. Implementation of a standardized protocol with strict eligibility criteria, objective quantifiable measurement of drug effect, and validated endpoints will eventually allow development of an ideal pharmacotherapy for IC.

Monitoring universal protocol compliance through real-time clandestine observation by medical students results in performance improvement.

OBJECTIVE: To measure universal protocol compliance through real-time, clandestine observation by medical students compared with chart audit reviews, and to enable medical students the opportunity to become conscious of the importance of medical errors and safety initiatives. DESIGN: With endorsement from Tufts Medical Center's (TMC's) Chief Medical Officer and Surgeon-in-Chief, 8 medical students performed clandestine observation audits of 98 cases from April to August 2009. A compliance checklist was based on TMC's presurgical checklist. Our initial results led to interventions to improve our universal protocol procedures, including modifications to the operating room white board and presurgical checklist, and specific feedback to surgical departments. One year later, 6 medical students performed observations of 100 cases from June to August 2010. SETTING: Tufts Medical Center, Boston, Massachusetts, which is an academic medical center and the principal teaching hospital for Tufts University School of Medicine. PARTICIPANTS: An operating room coordinator placed the medical students into 1 of our 25 operating rooms with students entering under the premise of observing the anesthesiologist for clinical education. The observations were performed Monday to Friday between 7 am and 4 pm. Although observations were not randomized, no single service or type of surgery was targeted for observation. RESULTS: A broad range of departments was observed. In 8.2% of cases, the surgical site was unmarked. A Time Out occurred in 89.7% of cases. The entire surgical team was attentive during the time out in 82% of cases. The presurgical checklist was incomplete before incision in 13 cases. Images were displayed in 82% of cases. The operating room "white board" was filled out completely in 49% of cases. Team introductions occurred in 13 cases. One year later, compliance increased in all Universal Protocol dimensions. CONCLUSIONS: Direct, real-time observation by medical students provides an accurate and granular assessment of compliance with specific components of the universal protocol and engages medical students in the quality improvement process, raises their awareness of the gravity of medical errors, and ensures appreciation of the importance of quality and safety initiatives.

The role of carotid revascularization in stroke prevention.

The goal of carotid disease management is prevention of stroke. Many randomized prospective trials of carotid disease management provide level-1 evidence to guide decision making to optimize stroke prevention in patients with carotid disease. Other patients present with clinical scenarios that fall outside the eligibility criteria for these clinical trials, and in these patients, clinical decisions must be based on the best available information on the natural history of each patient's carotid disease and on the clinician's assessment of the risks and benefits of intervention. In this monograph, the author reviews the current clinical data relating to carotid revascularization for asymptomatic carotid disease, for carotid disease with transient ischemic attack or minor stroke, and for carotid disease with acute stroke or stroke in evolution. Relevant clinical trials of carotid endarterectomy and carotid stenting are reviewed in detail. In addition, relevant natural history and risk-benefit data are reviewed to guide clinical decision making in patients whose clinical presentations fall outside the scope of the available clinical trials. The goal of this monograph is to provide the clinician with an evidence basis for clinical decision making in patients with commonly encountered carotid disease-related presentations.

Management of atherosclerotic carotid artery disease: clinical practice guidelines of the Society for Vascular Surgery.

The Society for Vascular Surgery (SVS) appointed a committee of experts to formulate evidence-based clinical guidelines for the management of carotid stenosis. In formulating clinical practice recommendations, the committee used systematic reviews to summarize the best available evidence and the GRADE scheme to grade the strength of recommendations (GRADE 1 for strong recommendations; GRADE 2 for weak recommendations) and rate the quality of evidence (high, moderate, low, and very low quality). In symptomatic and asymptomatic patients with low-grade carotid stenosis (<50% in symptomatic and <60% in asymptomatic patients), we recommend optimal medical therapy rather than revascularization (GRADE 1 recommendation, high quality evidence). In symptomatic patients with moderate to severe carotid stenosis (more than 50%), we recommend carotid endarterectomy plus optimal medical therapy (GRADE 1 recommendation, high quality evidence). In symptomatic patients with moderate to severe carotid stenosis (>/=50%) and high perioperative risk, we suggest carotid artery stenting as a potential alternative to carotid endarterectomy (GRADE 2 recommendation, low quality evidence). In asymptomatic patients with moderate to severe carotid stenosis (>/=60%), we recommend carotid endarterectomy plus medical management as long as the perioperative risk is low (GRADE 1 recommendation, high quality evidence). We recommend against carotid artery stenting for asymptomatic patients with moderate to severe (>/=60%) carotid artery stenosis (GRADE 1 recommendation, low quality evidence). A possible exception includes patients with >/=80% carotid artery stenosis and high anatomic risk for carotid endarterectomy.