Increased Mortality in Patients Transferred to a Level 1 Trauma Center with Blunt and Penetrating Extremity Vascular Injuries.

BACKGROUND: Trauma care depends on a complex transfer system to ensure timely and adequate management at major trauma centers. Patient outcomes depend on the reliability of triage in local or community hospitals and access to tertiary or quaternary trauma institutions. Patients with polytrauma, extremity trauma, or vascular injuries require multidisciplinary management at trauma hospitals. Our study investigated outcomes in this population at a level one trauma center in San Bernardino County, the largest geographic county in the contiguous United States. METHODS: We conducted a retrospective review of all patients with extremity trauma who presented to a single level 1 trauma center over 10 years. The cohort was divided into following two groups: 1. transferred from another medical center for a higher level of care or 2. those who directly presented. Overall, 19,417 patients were identified, with 15,317 patients presenting directly and 3,830 patients transferred from an outside hospital. Extremity of vascular injuries was observed in 268 patients. Demographic data were ascertained, including the injury severity score, mechanism of injury, response level, arrival method, tertiary center emergency department disposition, and presence of vascular injury in the upper or lower extremities. Univariate and multivariate analyses were performed to assess patient mortality. RESULTS: A total of 268 patients with vascular injuries were analyzed, including 207 nontransferred and 61 transferred patients. In the univariate analysis, injury severity score means were compared at 11.4 in nontransferred patients versus 8.4 in transferred (P < 0.001), 50% of blunt injury in the nontransferred group, and 28% in the transferred group (P < 0.001); in-hospital mortality was 4% in nontransferred patients versus 28% in the transferred group (P < 0.001). Multivariate logistic regression demonstrated that mortality is 8 times more likely if a patient with vascular extremity injuries is transferred from an outside hospital. A 10% mortality rate was observed in patients without blood transfusion within 4 hr of arrival to the trauma center and 3% mortality in transferred patients transfused blood. CONCLUSIONS: Extremity trauma with vascular injury can be lethal if managed appropriately. Patients transferred to our level 1 trauma center had a substantial increase in mortality compared with nontransferred patients. Furthermore, the transfer distance was associated with increased mortality. Further research is required to address this vulnerable patient population.

Effects of abdominal aortic aneurysm appropriateness dashboard on clinical practice.

OBJECTIVE: The Society for Vascular Surgery published abdominal aortic aneurysm (AAA) practice guidelines in 2003, 2009, and 2018 to improve the management and treatment of AAAs. In 2014, our vascular surgery department implemented a quarterly AAA dashboard (AAAdb) to record the perioperative outcomes and guideline compliance with a focus on intervention appropriateness and procedural follow-up, which supplemented our Vascular Quality Initiative data. From the available reported evidence and expert consensus opinions, nine additional criteria for the appropriate treatment of AAAs <5 cm in women and <5.5 cm in men were noted, when applicable. The purpose of our study was to assess the effects of AAAdb implementation on adherence to society and institutional guidelines, documentation of treatment rationale, and the quality of follow-up. METHODS: We performed a retrospective review of elective open and endovascular AAA repair at a single institution from 2010 to 2018. The AAAdb was implemented in the middle of this period in 2014. The patient demographics, aortic size, repair indication, repair type, 30-day mortality, and postoperative and 1-year follow-up imaging findings were analyzed. The primary outcome was adherence to intervention appropriateness and the follow-up guidelines. The categorical factors were summarized using frequencies and percentages and compared using the Pearson χ2 test or Fisher exact test. Continuous measures were summarized using the mean ± standard deviation and compared between study periods using two-sample t tests. RESULTS: From 2010 to 2018, 1549 patients had undergone elective AAA repair: 657 before and 892 after AAAdb implementation. No differences were found in AAA size after AAAdb (5.6 ± 1.2 cm vs 5.6 ± 1.1 cm; P = .88). However, the proportion of size-appropriate repairs increased (64.1% vs 71.3%; P = .003). The proportion of small AAA repairs with a documented rationale had increased (64.4% vs 80.5%; P < .001), with rapid disease progression cited most often. No difference was found in 30-day mortality (1.2% vs 1.5%; P = .69). Follow-up imaging after endovascular abdominal aortic aneurysm repair increased at <60 days postoperatively (76% vs 84%; P = .004) and at 1 year of follow-up (78% vs 86%; P = .0005). The proportion of patients with endoleak at <60 days postoperatively had increased in the post-AAAdb cohort (21% vs 29%; P = .012). CONCLUSIONS: The AAAdb served as a centerpiece for improving the appropriateness of care and compliance with national and institutional guidelines, including treatment of small AAAs in special circumstances. Its implementation was associated with higher quality follow-up and surveillance in a high-volume, regional aortic center. Consideration should be given to adding additional criteria to the Society for Vascular Surgery guidelines and Vascular Quality Initiative reporting.

A Comparative Analysis of Critical Limb Ischemia in the Intensive Care Unit since the COVID-19 Pandemic.

BACKGROUND: Emerging data and case reports have found coagulation abnormalities and thrombosis as sequelae of infection with SARS-CoV-2 (COVID-19). Case reports have reported thrombotic complications caused by COVID-19-related coagulopathy leading to limb loss. Alarmingly, many of these patients had no underlying vascular disease prior to being infected with COVID-19. Many of these case reports discuss patients developing gangrene in the intensive care unit (ICU). Our study compares the incidence of gangrene in the ICU in COVID-19 patients to baseline inpatient levels prior to the pandemic. METHODS: This retrospective analysis investigates two subsets of patients from a single institution. The first was from 2020 during the COVID-19 pandemic; the second subset was from 2019 before the pandemic. Demographic data and medication history were ascertained for both groups. Primary outcomes measures included extremity gangrene that developed in the ICU, mortality, and major amputation. RESULTS: There were 249 COVID-19 positive patients admitted to the ICU in 2020. In 2019, 1,846 admissions to the ICU took place, of which 249 patients were randomized to chart review. There were 13 cases of gangrene that developed in the ICU, 12 of which took place in 2020. In-hospital mortality was 11.6% in nonCOVID-19 patients in 2019 vs. 41.4% in 2021 (P < 0.001). Only 16.7% of the COVID-19 gangrene patients had previously known arterial disease. Also, patients in the COVID-19 group with gangrene were four times more likely to be smokers (P = 0.004). When the data were stratified to compare between gangrene development and no gangrene development, the combined total gangrene group had longer hospital stays, higher need for blood transfusions, required major amputations, and revascularization. A multivariate logistic regression from the total study similarly demonstrated that COVID-19 infection is associated with an 18.23 times increased risk of gangrene. CONCLUSIONS: COVID-19 has resulted in an incomprehensible societal impact that will linger for years to come. The last 2 years have reinforced that COVID-19 will be a part of our clinical practice indefinitely. This study emphasizes the importance of clinician awareness of COVID-19 induced critical limb ischemia in those without underlying arterial disease and few medical comorbidities. More research efforts toward preventing limb loss and COVID-19 coagulopathy must be performed expeditiously to achieve a better understanding.

Inhibition of VEGF (Vascular Endothelial Growth Factor)-A or its Receptor Activity Suppresses Experimental Aneurysm Progression in the Aortic Elastase Infusion Model.

OBJECTIVE: We examined the pathogenic significance of VEGF (vascular endothelial growth factor)-A in experimental abdominal aortic aneurysms (AAAs) and the translational value of pharmacological VEGF-A or its receptor inhibition in aneurysm suppression. Approaches and Results: AAAs were created in male C57BL/6J mice via intra-aortic elastase infusion. Soluble VEGFR (VEGF receptor)-2 extracellular ligand-binding domain (delivered in Ad [adenovirus]-VEGFR-2), anti-VEGF-A mAb (monoclonal antibody), and sunitinib were used to sequester VEGF-A, neutralize VEGF-A, and inhibit receptor tyrosine kinase activity, respectively. Influences on AAAs were assessed using ultrasonography and histopathology. In vitro transwell migration and quantitative reverse transcription polymerase chain reaction assays were used to assess myeloid cell chemotaxis and mRNA expression, respectively. Abundant VEGF-A mRNA and VEGF-A-positive cells were present in aneurysmal aortae. Sequestration of VEGF-A by Ad-VEGFR-2 prevented AAA formation, with attenuation of medial elastolysis and smooth muscle depletion, mural angiogenesis and monocyte/macrophage infiltration. Treatment with anti-VEGF-A mAb prevented AAA formation without affecting further progression of established AAAs. Sunitinib therapy substantially mitigated both AAA formation and further progression of established AAAs, attenuated aneurysmal aortic MMP2 (matrix metalloproteinase) and MMP9 protein expression, inhibited inflammatory monocyte and neutrophil chemotaxis to VEGF-A, and reduced MMP2, MMP9, and VEGF-A mRNA expression in macrophages and smooth muscle cells in vitro. Additionally, sunitinib treatment reduced circulating monocytes in aneurysmal mice. CONCLUSIONS: VEGF-A and its receptors contribute to experimental AAA formation by suppressing mural angiogenesis, MMP and VEGF-A production, myeloid cell chemotaxis, and circulating monocytes. Pharmacological inhibition of receptor tyrosine kinases by sunitinib or related compounds may provide novel opportunities for clinical aneurysm suppression.

Mid-Term Outcomes of Retroperitoneal and Transperitoneal Exposures in Open Aortic Aneurysm Repair.

BACKGROUND: There have been a number of studies comparing perioperative outcomes of the retroperitoneal (RP) and transperitoneal (TP) approaches to open aortic aneurysm repair (OAR), many of which have shown conflicting results. There remains a paucity of data comparing these 2 exposures beyond 30 days. The purpose of this study was to evaluate the mid-term outcomes between RP and TP exposures in OAR. METHODS: This is a retrospective review of elective OAR from a single institution from 2010 to 2014 with at least one year of follow-up. Patients with any prior aortic repair, prior midline TP or RP exposures, prior small bowel obstruction (SBO), or prior abdominal wall hernia repair were excluded. Patients' demographics, comorbidities, intraoperative details, and postoperative variables up to 5 years were compared. Primary outcomes were all-cause mortality, aortic or arterial reinterventions, incisional reinterventions, SBO or reintervention for SBO, and composite reintervention. RESULTS: Of the 273 OARs identified, 136 OARs (86 TP and 50 RP exposures) met criteria for the study. The average follow-up was 43.4 months. Of the preoperative and intraoperative characteristics, patients with RP exposures were significantly more likely to be female (30% vs. 12.8%; P = .014) and to have larger aneurysm (6.1 ± 1.02 cm vs. 5.4 ± 1.01 cm; P < .001), tube graft (48% vs 19.8%; P < .001), and renal bypass (30% vs. 2.3%; P < .001). Patients with TP exposures were significantly more likely to have inferior mesenteric artery reimplantation (15.1% vs. 4%; P = .046), infrarenal clamping (65.9% vs. 22%; P < .001), and iliac aneurysm (36% vs. 4%; P < .001). During mid-term follow-up, there was not a difference in all-cause survival at 3 years (95.8% vs. 95.8%; P = .52). Although there were more incisional hernias in the TP group (48% vs. 8%; P < .001), there was no difference in incisional reinterventions (14% vs. 6%; P = .36). There were no differences in aortic or arterial reinterventions (5% vs. 4%; P = .86), SBO (7% vs. 0%; P = .99), intervention for SBO (3% vs. 0%; P = .99), or composite reinterventions (16% vs. 10%; P = .6) between the TP and RP exposures. CONCLUSIONS: In mid-term follow-up, OAR through TP exposure had more incisional hernias compared with RP exposure. However, there is no difference in mortality or composite reinterventions between approaches.

Metformin treatment status and abdominal aortic aneurysm disease progression.

OBJECTIVE: In population-based studies performed on multiple continents during the past two decades, diabetes mellitus has been negatively associated with the prevalence and progression of abdominal aortic aneurysm (AAA) disease. We investigated the possibility that metformin, the primary oral hypoglycemic agent in use worldwide, may influence the progression of AAA disease. METHODS: Preoperative AAA patients with diabetes were identified from an institutional database. After tabulation of individual cardiovascular and demographic risk factors and prescription drug regimens, odds ratios for categorical influences on annual AAA enlargement were calculated through nominal logistical regression. Experimental AAA modeling experiments were subsequently performed in normoglycemic mice to validate the database-derived observations as well as to suggest potential mechanisms of metformin-mediated aneurysm suppression. RESULTS: Fifty-eight patients met criteria for study inclusion. Of 11 distinct classes of medication considered, only metformin use was negatively associated with AAA enlargement. This association remained significant after controlling for gender, age, cigarette smoking status, and obesity. The median enlargement rate in AAA patients not taking oral diabetic medication was 1.5 mm/y; by nominal logistic regression, metformin, hyperlipidemia, and age ≥70 years were associated with below-median enlargement, whereas sulfonylurea therapy, initial aortic diameter ≥40 mm, and statin use were associated with above-median enlargement. In experimental modeling, metformin dramatically suppressed the formation and progression, with medial elastin and smooth muscle preservation and reduced aortic mural macrophage, CD8 T cell, and neovessel density. CONCLUSIONS: Epidemiologic evidence of AAA suppression in diabetes may be attributable to concurrent therapy with the oral hypoglycemic agent metformin.

Peptide inhibitor of CXCL4-CCL5 heterodimer formation, MKEY, inhibits experimental aortic aneurysm initiation and progression.

OBJECTIVE: Macrophages are critical contributors to abdominal aortic aneurysm (AAA) disease. We examined the ability of MKEY, a peptide inhibitor of CXCL4-CCL5 interaction, to influence AAA progression in murine models. APPROACH AND RESULTS: AAAs were created in 10-week-old male C57BL/6J mice by transient infrarenal aortic porcine pancreatic elastase infusion. Mice were treated with MKEY via intravenous injection either (1) before porcine pancreatic elastase infusion or (2) after aneurysm initiation. Immunostaining demonstrated CCL5 and CCR5 expression on aneurysmal aortae and mural monocytes/macrophages, respectively. MKEY treatment partially inhibited migration of adaptively transferred leukocytes into aneurysmal aortae in recipient mice. Although all vehicle-pretreated mice developed AAAs, aneurysms formed in only 60% (3/5) and 14% (1/7) of mice pretreated with MKEY at 10 and 20 mg/kg, respectively. MKEY pretreatment reduced aortic diameter enlargement, preserved medial elastin fibers and smooth muscle cells, and attenuated mural macrophage infiltration, angiogenesis, and aortic metalloproteinase 2 and 9 expression after porcine pancreatic elastase infusion. MKEY initiated after porcine pancreatic elastase infusion also stabilized or reduced enlargement of existing AAAs. Finally, MKEY treatment was effective in limiting AAA formation after angiotensin II infusion in apolipoprotein E-deficient mice. CONCLUSIONS: MKEY suppresses AAA formation and progression in 2 complementary experimental models. Peptide inhibition of CXCL4-CCL5 interactions may represent a viable translational strategy to limit progression of human AAA disease.

The novel use of resuscitative endovascular balloon occlusion of the aorta for uncontrolled bleeding in a surgically inaccessible abdomen: The ruptured proper hepatic artery in a frozen abdomen.

Hemorrhage is among the leading causes of death for trauma patients. Adjunct techniques used to control bleeding include use of aortic cross clamping, application of a pelvic binder, rapidly expanding hemostatic sponges, and extra-peritoneal packing. Additionally, Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA) can provide life-saving proximal control for patients with massive internal hemorrhage. This study concerns a patient treated with Zone 1 REBOA for class IV hemorrhagic shock from a spontaneous common hepatic artery rupture. REBOA was performed at bedside in the Surgical Intensive Care Unit (SICU) prior to definitive selective embolization. A healthy 28-year-old male suffered a grade 4 liver laceration and pancreatic head transection with associated duodenal injury after a high-speed motor vehicle collision. On arrival, the patient required a damage control laparotomy with multiple reoperations for management of his intra-abdominal injuries. By hospital day 11, significant visceral adhesions resulted in a frozen abdomen. On hospital day 20, the patient developed massive hematemesis, hematochezia, and class IV hemorrhagic shock. Vascular surgery was called to bedside in the SICU to perform REBOA. The patient received massive transfusion protocol while a 12 Fr sheath was inserted, and an aortic occlusion balloon was inflated in Zone 1 allowing for hemodynamic stabilization for transport and definitive management in the angiography suite. This case reports a novel use of REBOA, at bedside in the SICU, for the management of a massive gastrointestinal bleed in a patient with frozen abdomen. In this case, REBOA allowed us to achieve temporary hemodynamic stability prior to definitive control in the angiography suite. Bedside use of REBOA in the SICU prevented certain exsanguination and death.

Recombinant Interleukin-19 Suppresses the Formation and Progression of Experimental Abdominal Aortic Aneurysms.

Background Interleukin-19 is an immunosuppressive cytokine produced by immune and nonimmune cells, but its role in abdominal aortic aneurysm (AAA) pathogenesis is not known. This study aimed to investigate interleukin-19 expression in, and influences on, the formation and progression of experimental AAAs. Methods and Results Human specimens were obtained at aneurysm repair surgery or from transplant donors. Experimental AAAs were created in 10- to 12-week-old male mice via intra-aortic elastase infusion. Influence and potential mechanisms of interleukin-19 treatment on AAAs were assessed via ultrasonography, histopathology, flow cytometry, and gene expression profiling. Immunohistochemistry revealed augmented interleukin-19 expression in both human and experimental AAAs. In mice, interleukin-19 treatment before AAA initiation via elastase infusion suppressed aneurysm formation and progression, with attenuation of medial elastin degradation, smooth-muscle depletion, leukocyte infiltration, neoangiogenesis, and matrix metalloproteinase 2 and 9 expression. Initiation of interleukin-19 treatment after AAA creation limited further aneurysmal degeneration. In additional experiments, interleukin-19 treatment inhibited murine macrophage recruitment following intraperitoneal thioglycolate injection. In classically or alternatively activated macrophages in vitro, interleukin-19 downregulated mRNA expression of inducible nitric oxide synthase, chemokine C-C motif ligand 2, and metalloproteinases 2 and 9 without apparent effect on cytokine-expressing helper or cytotoxic T-cell differentiation, nor regulatory T cellularity, in the aneurysmal aorta or spleen of interleukin-19-treated mice. Interleukin-19 also suppressed AAAs created via angiotensin II infusion in hyperlipidemic mice. Conclusions Based on human evidence and experimental modeling observations, interleukin-19 may influence the development and progression of AAAs.