Novel Tissue Factor Inhibition for Thromboprophylaxis in COVID-19: Primary Results of the ASPEN-COVID-19 Trial.

BACKGROUND: Thrombo-inflammation is central to COVID-19-associated coagulopathy. TF (tissue factor), a driver of disordered coagulation and inflammation in viral infections, may be a therapeutic target in COVID-19. The safety and efficacy of the novel TF inhibitor rNAPc2 (recombinant nematode anticoagulation protein c2) in COVID-19 are unknown. METHODS: ASPEN-COVID-19 was an international, randomized, open-label, active comparator clinical trial with blinded end point adjudication. Hospitalized patients with COVID-19 and elevated D-dimer levels were randomized 1:1:2 to lower or higher dose rNAPc2 on days 1, 3, and 5 followed by heparin on day 8 or to heparin per local standard of care. In comparisons of the pooled rNAPc2 versus heparin groups, the primary safety end point was major or nonmajor clinically relevant International Society of Thrombosis and Haemostasis bleeding through day 8. The primary efficacy end point was proportional change in D-dimer concentration from baseline to day 8, or discharge if before day 8. Patients were followed for 30 days. RESULTS: Among 160 randomized patients, median age was 54 years, 43.1% were female, and 38.8% had severe baseline COVID-19. There were no significant differences between rNAPc2 and heparin in bleeding or other safety events. Overall, median change in D-dimer was -16.8% (interquartile range, -45.7 to 36.8; P=0.41) with rNAPc2 treatment and -11.2% (-36.0 to 34.4; P=0.91) with heparin (Pintergroup=0.47). In prespecified analyses, in severely ill patients, D-dimer levels tended to increase more within the heparin (median, 29.0% [-14.9 to 145.2]; P=0.02) than the rNAPc2 group (median, 25.9% [-49.1 to 136.4]; P=0.14; Pintergroup=0.96); in mildly ill patients, D-dimer levels were reduced within each group with a numerically greater reduction with rNAPc2 versus heparin (rNAPc2 median, -32.7% [-44.7 to 4.3]; P=0.007 and heparin median, -16.8% [-36.0 to 0.5]; P=0.008, Pintergroup=0.34). CONCLUSIONS: rNAPc2 treatment in hospitalized patients with COVID-19 was well tolerated without excess bleeding or serious adverse events but did not significantly reduce D-dimer more than heparin at day 8. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT04655586.

Readmission after early thoracic endovascular aortic repair versus medical management of acute type B aortic dissection.

BACKGROUND: The use of thoracic endovascular aortic repair (TEVAR) for the management of acute uncomplicated type B aortic dissection (TBAD) has increased. Although the results from early studies were promising, larger randomized trials evaluating TEVAR are lacking. It is also unclear where sufficient equipoise exists for such trials. In the present study, we evaluated the number of readmissions and unplanned operations after TEVAR vs those after medical management as the initial treatment of acute uncomplicated TBAD and the frequency of each treatment in this population. METHODS: We performed a multi-institutional retrospective review of patients with acute TBAD from 2015 to 2020 with the 1-year outcomes available, excluding patients with prior aortic intervention or chronic, iatrogenic or traumatic etiologies. The primary exposure was TEVAR vs medical management at the index admission. The patient demographics, clinical presentation, and imaging findings were analyzed using bivariate and multivariate logistic regression for the primary outcomes of unplanned readmission and/or operation after the initial admission. The secondary outcomes were mortality, myocardial infarction, stroke, renal failure requiring dialysis, retrograde type A dissection, and length of stay. We hypothesized that the readmissions would be higher with medical management. RESULTS: A total of 216 patients with TBAD (47 with complicated and 169 with uncomplicated) from two large academic centers were identified. Of the 169 patients with uncomplicated TBAD, 83 (49%) had been treated medically and 86 (51%) had undergone TEVAR at the initial admission. No differences were found in the demographics or high-risk imaging features at presentation. The medically managed patients had had higher rates of unplanned readmission (34% vs 9%; P = .0001) and operation (28% vs 8%; P = .0007) but shorter lengths of stay (6.3 vs 13.1 days; P < .0001). No differences were found in mortality, although the rate of myocardial infarction was higher in the medically managed group (10.8% vs 2.3%; P = .02). Although 28% of the medically managed patients had later required operation, they had had morbidity and mortality similar to those of patients who had undergone initial TEVAR. Initial medical management was associated with unplanned readmission (odds ratio, 8.3; P = .02) and the need for operation (odds ratio, 4.56; P = .006). No differences were found in the outcomes according to the involved aortic zones. CONCLUSIONS: In the present study, medical management of acute uncomplicated TBAD was associated with higher rates of readmission and the need for unplanned operation compared with TEVAR. However, no differences were found in the 1-year mortality for the patients for whom medical management had failed. Because one half of the patients had undergone medical management and one half had undergone early TEVAR, this finding suggests clinical equipoise for the treatment of acute uncomplicated TBAD. Therefore, a larger randomized trial appears warranted to determine whether a clear benefit exists for early TEVAR.

Factors associated with successful median arcuate ligament release in an international, multi-institutional cohort.

OBJECTIVE: Prior research on median arcuate ligament syndrome has been limited to institutional case series, making the optimal approach to median arcuate ligament release (MALR) and resulting outcomes unclear. In the present study, we compared the outcomes of different approaches to MALR and determined the predictors of long-term treatment failure. METHODS: The Vascular Low Frequency Disease Consortium is an international, multi-institutional research consortium. Data on open, laparoscopic, and robotic MALR performed from 2000 to 2020 were gathered. The primary outcome was treatment failure, defined as no improvement in median arcuate ligament syndrome symptoms after MALR or symptom recurrence between MALR and the last clinical follow-up. RESULTS: For 516 patients treated at 24 institutions, open, laparoscopic, and robotic MALR had been performed in 227 (44.0%), 235 (45.5%), and 54 (10.5%) patients, respectively. Perioperative complications (ileus, cardiac, and wound complications; readmissions; unplanned procedures) occurred in 19.2% (open, 30.0%; laparoscopic, 8.9%; robotic, 18.5%; P < .001). The median follow-up was 1.59 years (interquartile range, 0.38-4.35 years). For the 488 patients with follow-up data available, 287 (58.8%) had had full relief, 119 (24.4%) had had partial relief, and 82 (16.8%) had derived no benefit from MALR. The 1- and 3-year freedom from treatment failure for the overall cohort was 63.8% (95% confidence interval [CI], 59.0%-68.3%) and 51.9% (95% CI, 46.1%-57.3%), respectively. The factors associated with an increased hazard of treatment failure on multivariable analysis included robotic MALR (hazard ratio [HR], 1.73; 95% CI, 1.16-2.59; P = .007), a history of gastroparesis (HR, 1.83; 95% CI, 1.09-3.09; P = .023), abdominal cancer (HR, 10.3; 95% CI, 3.06-34.6; P < .001), dysphagia and/or odynophagia (HR, 2.44; 95% CI, 1.27-4.69; P = .008), no relief from a celiac plexus block (HR, 2.18; 95% CI, 1.00-4.72; P = .049), and an increasing number of preoperative pain locations (HR, 1.12 per location; 95% CI, 1.00-1.25; P = .042). The factors associated with a lower hazard included increasing age (HR, 0.99 per increasing year; 95% CI, 0.98-1.0; P = .012) and an increasing number of preoperative diagnostic gastrointestinal studies (HR, 0.84 per study; 95% CI, 0.74-0.96; P = .012) Open and laparoscopic MALR resulted in similar long-term freedom from treatment failure. No radiographic parameters were associated with differences in treatment failure. CONCLUSIONS: No difference was found in long-term failure after open vs laparoscopic MALR; however, open release was associated with higher perioperative morbidity. These results support the use of a preoperative celiac plexus block to aid in patient selection. Operative candidates for MALR should be counseled regarding the factors associated with treatment failure and the relatively high overall rate of treatment failure.

Morbidity and Long-Term Patient-Reported Outcomes Following Advanced Carotid Body Tumor Resection.

BACKGROUND: The reported risk of a cranial nerve (CN) injury is up to 1 in 4 patients in large registries of carotid body tumor (CBT) resection. Functional outcome for this population is unknown. METHODS: We evaluated consecutive patients who underwent CBT resection from November 2013 through October 2020. Demographics, intraoperative details, complications, and outcomes were recorded from the medical record. Permanent CN nerve injury was defined as deficits lasting >6 months. Frequency statistics, averages, chi-squared test, and multiple logistic regression were completed for primary end points of complications and disease-free survival. Patient-reported outcomes were gathered via telephone survey of patients conducted in September 2021. RESULTS: Fifty-one patients presented with CBTs and the following Shamblin classes: I (n = 7; 14%), II (n = 36; 69%), and III (n = 9; 17%). Head and neck oncology and vascular surgery jointly did 52% of CBT resections, including 6 of 9 Shamblin III cases. Eight patients (15.3%, all Shamblin II or III) suffered a total of 12 CN injuries - 8 CN XII (5 temporary and 3 permanent), 3 CN X (all permanent), and 1 CN XI (permanent). Seven of the CN injury subgroup had preoperative embolization and 5 were joint oncology/vascular cases. In addition, 4 separate carotid injuries required repair. Notably, all patients had disease-free survival postoperatively at a mean follow-up of 6 months. Patient-reported outcomes obtained in 70.6% of patients 1 year or more from index operation demonstrated that two-thirds of patients live without any permanent functional deficits, and the majority of those with continued deficits rate the symptoms as daily but mild in severity. CONCLUSIONS: In a series of complex CBT patients treated with preoperative embolization capabilities and multidisciplinary surgical approach, disease-free survival was achieved in all patients despite a high rate of iatrogenic CN injuries, most commonly CN XII. Patient-reported outcomes survey results indicate that injuries identified on clinical exam underreport patients' true postoperative CN deficits - especially branches of CN X. This data support the practice of aggressive primary resection of CBTs while providing guidance for expected functional outcomes due to CN injury risk.

Critical appraisal of the contemporary use of atherectomy to treat femoropopliteal atherosclerotic disease.

OBJECTIVE: Atherectomy has become increasingly used as an endovascular treatment of lower extremity atherosclerotic disease in the United States. However, concerns and controversies about its indications and outcomes exist. The goal of the present systematic review and meta-analysis was to investigate the outcomes and complications related to atherectomy to treat femoropopliteal atherosclerotic disease. METHODS: A systematic review in accordance with the recommendations from the PRISMA (preferred reporting items for systematic reviews and meta-analyses) statement was performed. Four major scientific repositories (MEDLINE, Embase, the Cochrane Library, and Thompson Web of Sciences) were queried from their inception to April 5, 2020. We reviewed and entered the data in a dedicated dataset. The outcomes included the patency rates, clinical and hemodynamic improvement, and morbidity and mortality associated with atherectomy interventions. RESULTS: Twenty-four studies encompassing 1900 patients met the inclusion criteria for the present study. Of the 1900 patients, 74.3% had presented with Rutherford class 1 to 3 and 25.7% presented with Rutherford class 4 to 6; 1445 patients had undergone atherectomy, and 455 patients had been treated without atherectomy. The atherectomy group had undergone directional atherectomy (n = 851), rotational atherectomy (n = 851), laser atherectomy (n = 201), and orbital atherectomy (n = 78). Most of these patients had also received adjunct treatments, which varied across the studies and included a combination of stenting, balloon angioplasty, or drug-coated balloon angioplasty. Technical success was achieved in 92.3% of the cases. Distal embolization, vessel perforation, and dissection occurred in 3.4%, 1.9%, and 4% of the cases, respectively. The initial patency was 95.4%. At the 12-month median follow-up, the primary patency was 72.6%. The ankle brachial index had improved from a preoperative mean of 0.6 to a postoperative mean of 0.84. The incidence of major amputation and mortality during the follow-up period was 2.2% and 3.4%, respectively. CONCLUSIONS: The results from our review of the reported data suggest that femoropopliteal atherectomy can be completed safely, modestly improving the ankle brachial index and maintaining the 1-year patency in nearly three of four patients. However, these findings were based on heterogeneous studies that skewed the generalizable conclusions about atherectomy's efficacy. Atherectomy places a high cost burden on the healthcare system and is used in the United States at a higher rate than in other countries. Our review of the literature did not demonstrate clear atherectomy superiority to alternatives that would warrant the pervasive and increasing use of this costly technology. Future work should focus on developing high-quality randomized controlled trials to determine the specific patient and lesion characteristics for which atherectomy can add value.

High Rates of Recurrent Revascularization in Acute Limb Ischemia - A National Surgical Quality Improvement Program Study.

BACKGROUND: We queried the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database to review outcomes of acute limb ischemia (ALI) patients following open surgical intervention for ALI. METHODS: A previously validated tool was used to identify ALI patients in NSQIP undergoing open surgical revascularization from 2012 to 2017. Multivariable analysis was performed for the primary outcome of reoperation and secondary outcome of readmission and infection. RESULTS: A total of 2,878 ALI patients underwent open revascularization; 35.7% were transfers from another acute care hospital. A total of 13.8% required reoperation and 7.9% required readmission within 30 days. A total of 32% of reoperations were recurrent revascularization, representing 4.4% of all ALI patients. A total of 58.7% of patients were female and either overweight or obese. Younger age (odds ratio OR 0.991 [0.984-0.999], P = 0.02), underweight patients (OR 1.159 [0.667-2.01], P = 0.05), pre-operative steroid use (OR 1.61 [1.07-2.41], P = 0.02), and perioperative transfusion (OR 2.02 [1.04-3.95], P = 0.04) predicted reoperations. CONCLUSIONS: This registry series demonstrates all-cause ALI patients are a different population than PAD with different risk factors. Despite being a time-critical condition, ALI has higher interhospital transfer rates than ACS or ruptured aneurysm. Following open revascularization, ALI outcomes are worse than ACS but better than ruptured AAA. These outcomes do not appear related to patient factors in contrast to revascularization for chronic PAD.

A comprehensive review on antithrombotic therapy for peripheral artery disease.

Peripheral artery disease (PAD) is a morbid and costly disease that can result in loss of limb and life if not managed appropriately with risk factor modification, antithrombotic therapy, and revascularization when necessary. Antithrombotic therapy includes antiplatelet and anticoagulant drugs. Antiplatelet agents used in PAD can include aspirin, reversible and irreversible P2Y12 inhibitors, and PAR-1 antagonists. These drugs are prescribed as both monotherapy or dual-antiplatelet therapy and are critical components of pre- and post-revascularization maintenance. Anticoagulants, such as vitamin K antagonists and heparin products, have long been used in cardiac disease; in patients with PAD, these drugs have been largely supplanted by new direct factor Xa antagonists, which offer superior safety profiles and reduced adverse events after revascularization. Anticoagulants are often used alongside antiplatelet medications after PAD revascularization; however, there is a lack of guideline consensus about therapy selection and large regional disparity in regard to antithrombotic prescribing patterns. In this review, we analyze the existing literature and guidelines regarding the use of antithrombotic therapy in patients with PAD and offer a framework to aid clinicians' decision making regarding therapy selection and duration based on current existing evidence.

Utilization of lean project management principles and health informatics to reduce operating room delays in a vascular surgery practice.

OBJECTIVES: Perioperative inefficiency can increase cost. We describe a process improvement initiative that addressed preoperative delays on an academic vascular surgery service. METHODS: First case vascular surgeries from July 2019-January 2020 were retrospectively reviewed for delays, defined as late arrival to the operating room (OR). A stakeholder group spearheaded by a surgeon-informaticist analyzed this process and implemented a novel electronic medical records (EMR) preoperative tool with improved preoperative workflow and role delegation; results were reviewed for 3 months after implementation. RESULTS: 57% of cases had first case on-time starts with average delay of 19 min. Inappropriate preoperative orders were identified as a dominant delay source (average delay = 38 min). Three months post-implementation, 53% of first cases had on-time starts with average delay of 11 min (P < 0.05). No delays were due to missing orders. CONCLUSIONS: Inconsistent preoperative workflows led to inappropriate orders and delays, increasing cost and decreasing quality. A novel EMR tool subsequently reduced delays with projected savings of $1,200/case. Workflow standardization utilizing informatics can increase efficiency, raising the value of surgical care.

The impact of the COVID-19 pandemic on vascular surgery: Health care systems, economic, and clinical implications.

The novel severe acute respiratory syndrome coronavirus-2 (coronavirus disease 2019 [COVID-19]) pandemic is responsible for more than 500,000 deaths in the United States and nearly 3 million worldwide, profoundly altering the landscape of health care delivery. Aggressive public health measures were instituted and hospital efforts became directed at COVID-19-related concerns. Consequently, routine surgical practice was virtually halted, resulting in billions of dollars in hospital losses as pandemic costs escalated. Navigating an uncertain new landscape of scarce resource allocation, exposure risk, role redeployment, and significant practice pattern changes has been challenging. Furthermore, the overall effect on the financial viability of the health care system and vascular surgical practices is yet to be elucidated. This review explores the economic and clinical implications of COVID-19 on the practice of vascular surgery in addition to the health care system as a whole.

Epidemiology of end-stage kidney disease.

End-stage kidney disease (ESKD) is a common and morbid disease that affects patients' quality and length of life, representing a large portion of health care expenditure in the United States. These patients commonly have associated diabetes and cardiovascular disease, with high rates of cardiovascular-related death. Management of ESKD requires renal replacement therapy via dialysis or transplantation. While transplantation provides the greatest improvement in survival and quality of life, the vast majority of patients are treated initially with hemodialysis. However, outcomes differ significantly among patient populations. Barriers in access to care have particularly affected at-risk populations, such as Black and Hispanic patients. These patients receive less pre-ESKD nephrology care, are less likely to initiate dialysis with a fistula, and wait longer for transplants-even in pediatric populations. Priorities for ESKD care moving into the future include increasing access to nephrology care in underprivileged populations, providing patient-centered care based on each patient's "life plan," and focusing on team-based approaches to ESKD care. This review explores ESKD from the perspective of epidemiology, costs, vascular access, patient-reported outcomes, racial disparities, and the impact of the COVID-19 crisis.

Efficacy of Negative Pressure Wound Treatment in Preventing Surgical Site Infections after Whipple Procedures.

Surgical site infections (SSIs) occur at an average rate of 21.1 per cent after Whipple procedures per NSQIP data. In the setting of adherence to standard National Surgery Quality Improvement Program (NSQIP) Hepatopancreatobiliary recommendations including wound protector use and glove change before closing, this study seeks to evaluate the efficacy of using negative pressure wound treatment (NPWT) over closed incision sites after a Whipple procedure to prevent SSI formation. We retrospectively examined consecutive patients from January 2014 to July 2016 who met criteria of completing Whipple procedures with full primary incision closure performed by a single surgeon at a single institution. Sixty-one patients were included in the study between two cohorts: traditional dressing (TD) (n = 36) and NPWT dressing (n = 25). There was a statistically significant difference (P = 0.01) in SSI formation between the TD cohort (n = 15, SSI rate = 0.41) and the NPWT cohort (n = 3, SSI rate = 0.12). The adjusted odds ratio (OR) of SSI formation was significant for NPWT use [OR = 0.15, P = 0.036] and for hospital length of stay [OR = 1.21, P = 0.024]. Operative length, operative blood loss, units of perioperative blood transfusion, intraoperative gastrojejunal tube placement, preoperative stent placement, and postoperative antibiotic duration did not significantly impact SSI formation (P > 0.05).

Evaluation of Preoperative Weight Loss for Elective Hernia Repair in the Veteran Population.

The safety and efficacy of preoperative weight loss before elective nonbariatric surgery is controversial. We evaluated the effect of planned surgical delay for a preoperative weight loss trial in hernia repairs. Four hundred and fourteen patients undergoing elective hernia repair between July 2008 and May 2012 at a Level 1B VA Medical Center were identified. Included patients were divided into two groups: those who underwent immediate hernia repair (nontrial) and those who underwent weight loss trial before hernia repair (TRIAL). Twenty-two patients were categorized in the TRIAL group, and 392 in nontrial. Time from surgical evaluation to operation was longer in the TRIAL vs nontrial group (226 days vs 113 days, P = 0.001). Outcome measures were similar between groups. Net change in body mass index (BMI) was -2.2 per cent in TRIAL vs -0.86 per cent in nontrial patients (P = 0.440). Of the TRIAL patients, ten obtained a poor result (<3% decreased BMI), nine a moderate result (3-10% decreased BMI), and three a good result (>10% decreased BMI). Weight loss trials in elective hernia patients appear to be safe, although they result in significant delay to surgery and confer no difference in postoperative outcomes. Thus, efficacy of preoperative weight loss trials may be limited.

The Effect of Applicant Publication Volume on the Orthopaedic Residency Match.

BACKGROUND: Research is an important factor used in evaluating applicants to orthopaedic training programs. Current reports regarding the publication rate among prospective residents are likely inaccurate. It is unknown whether research productivity is weighted more heavily at programs affiliated with research-driven institutions. OBJECTIVE: To establish accurate baseline data on publication rate among matched applicants to orthopaedic residency programs and to compare publication rates between applicants who matched at research-focused institutions and those who matched elsewhere. DESIGN: We performed a literature search for each U.S. resident in the 2013-2014 intern class. Number of publications: (1) in total, (2) in orthopaedic journals, and (3) as first/last author were recorded. Publication rate at the top 25 programs (according to medical school and departmental National Institutes of Health [NIH] funding and U.S. News ranking) was compared statistically against all others. RESULTS: Average number of publications per intern for all programs was 1.28 ± 0.15. Number of total and first/last author publications was significantly greater for programs affiliated with medical schools and departments in the top 25 for NIH funding, and at schools in the top 25 U.S. News rankings. Publication rate in orthopaedic journals was significantly higher for programs affiliated with departments in the top 25 for NIH funding and at top 25 U.S. News medical schools. CONCLUSIONS: The average matched applicant to an orthopaedic residency program publishes in the peer-reviewed literature less frequently than previously reported. Matched applicants at research-focused institutions tended to have more publications than those who matched at other programs.

Total Knee Arthroplasty Failure Induced by Metal Hypersensitivity.

BACKGROUND: Metal hypersensitivity is an uncommon complication after total knee arthroplasty (TKA) that can lead to significant functional impairment and aseptic prosthesis failure. CASE REPORT: We describe a 70-year-old patient who presented with persistent pain, swelling, and instability 2 years after a primary TKA. The patient had a history of metal hypersensitivity following bilateral metal-on-metal total hip arthroplasty (THA) that was revised to ceramic-on-polyethylene implants. Knee radiographs showed severe osteolysis with implant loosening. Serum cobalt was elevated and serum chromium was significantly elevated, while joint aspiration and inflammatory marker levels ruled out a periprosthetic infection. Revision TKA was performed, with intraoperative tissue pathology and postoperative leukocyte transformation testing confirming metal hypersensitivity as the cause for aseptic implant failure. CONCLUSIONS: This case report demonstrates the clinical and laboratory signs that suggest metal hypersensitivity in total knee arthroplasty and the potential for joint function restoration with revision surgery.