Expression of human tissue factor pathway inhibitor on vascular smooth muscle cells inhibits secretion of macrophage migration inhibitory factor and attenuates atherosclerosis in ApoE-/- mice.

BACKGROUND: Tissue factor (TF) and coagulation proteases are involved in promoting atherosclerosis, but the molecular and cellular bases for their involvement are unknown. METHODS AND RESULTS: We generated a new strain (ApX4) of apolipoprotein E-deficient mice expressing a membrane-tethered human tissue factor pathway inhibitor fusion protein on smooth muscle actin-positive cells, including vascular smooth muscle cells (SMCs). ApX4 mice developed little atherosclerosis on either a normal chow or high-fat diet. Lipid levels were similar to those in parental ApoE(-/-) mice, and there was no detectable difference in systemic (circulating) tissue factor pathway inhibitor levels or activity. The small lipid-rich lesions that developed had markedly reduced leukocyte infiltrates, and in contrast to ApoE(-/-) mice, SMCs did not express macrophage migratory inhibitory factor (MIF), including at sites distant from atheromatous lesions. Low levels of circulating MIF in ApX4 mice normalized to levels seen in ApoE(-/-) mice after injection of an inhibitory anti-human tissue factor pathway inhibitor antibody, which also led to MIF expression by tissue factor-positive medial SMCs. MIF production by SMCs in ApoE(-/-) mice in vitro and in vivo was shown to be dependent on tissue factor and protease-activated receptor signaling, which were inhibited in ApX4 mice. CONCLUSIONS: Our data indicate that tissue factor plays a hitherto unreported role in the generation of MIF by SMCs in atherosclerosis-prone ApoE(-/-) mice, inhibition of which significantly prevents the development of atherosclerosis, through inhibition of leukocyte recruitment. These data significantly enhance our understanding of the pathophysiology of this important pathology and suggest new potential translational strategies to prevent atheroma formation.

Postsurgical hemodynamics of the aortic valve bypass operation evaluated with phase contrast magnetic resonance.

PURPOSE: To characterize the postsurgical hemodynamics in aortic valve bypass (AVB) patients, and to determine the relationship between presurgical native aortic valve pressure gradient and postsurgical hemodynamics. MATERIALS AND METHODS: Twenty patients scheduled for AVB surgery underwent presurgical transthoracic Doppler echocardiography to assess the degree of aortic stenosis and postsurgical cardiac magnetic resonance imaging (MRI) to acquire phase contrast magnetic resonance (PCMR) flow values along the ascending and descending aorta, and in the conduit. Net flow values were calculated from the PCMR images and compared to presurgical aortic valve pressure gradient measurements. RESULTS: PCMR showed that: 1) The blood flow split between the aorta and the conduit was 35%:65% of cardiac output and 2) 60% of patients had net retrograde blood flow in the superior thoracic aorta over the cardiac cycle. Patients with presurgical pressure gradient (ΔP) > 45 mmHg had significantly less blood flow out of the native aorta than patients with ΔP < 45 mmHg, and had significantly more retrograde flow in the superior thoracic aorta postsurgery. CONCLUSION: In patients undergoing AVB, presurgical aortic valve pressure gradient is associated with the volume of blood flow out the aorta and the direction of blood flow in the superior thoracic aorta after conduit addition as measured by PCMR.

Comparison of Contralateral vs Ipsilateral Vein Graft for Traumatic Vascular Injury Repair: A Cohort From PROOVIT.

Traumatic injury leading to arterial damage has traditionally been repaired using autologous vein graft from the contralateral limb. This often requires a secondary surgical site and the potential of prolonged operative time for patients. We sought to assess the use of ipsilateral vs contralateral vein grafts in patients who experienced traumatic extremity vascular injury. A multicenter database was queried to identify arterial injuries requiring operative intervention with vein grafting. The primary outcome of interest was need for operative reintervention. Secondary outcomes included risk of thrombosis, infection, and intensive care unit length of stay. 358 patients (320 contralateral and 38 ipsilateral) were included in the analysis. The ipsilateral vein cohort did not display a statistically significant decrease in need for reoperation when compared to the contralateral group (11% vs 23%; OR 0.41, 95% CI -0.07-1.3; P = .14). Contralateral repair was associated with longer median intensive care unit (ICU) LOS (4.3 vs 3.1 days; P < .01).

Quantifying the benefit of whole blood on mortality in trauma patients requiring emergent laparotomy.

BACKGROUND: Whole blood (WB) transfusions in trauma represent an increasingly utilized resuscitation strategy in trauma patients. Previous reports suggest a probable mortality benefit with incorporating WB into massive transfusion protocols. However, questions surrounding optimal WB practices persist. We sought to assess the association between the proportion of WB transfused during the initial resuscitative period and its impact on early mortality outcomes for traumatically injured patients. METHODS: We performed a retrospective analysis of severely injured patients requiring emergent laparotomy and ≥3 units of red blood cell containing products (WB or packed red blood cells) within the first hour from an ACS Level I Trauma Center (2019-2022). Patients were evaluated based on the proportion of WB they received compared with packed red blood cells during their initial resuscitation (high ratio cohort ≥50% WB vs. low ratio cohort <50% WB). Multilevel Bayesian regression analyses were performed to calculate the posterior probabilities and risk ratios (RR) associated with a WB predominant resuscitation for early mortality outcomes. RESULTS: Two hundred sixty-six patients were analyzed (81% male; mean age, 36 years; 61% penetrating injury; mean Injury Severity Score, 30). The mortality was 11% at 4 hours and 14% at 24 hours. The high ratio cohort demonstrated a 99% (RR, 0.12; 95% credible interval, 0.02-0.53) and 99% (RR, 0.22; 95% credible interval, 0.08-0.65) probability of decreased mortality at 4 hours and 24 hours, respectively, compared the low ratio cohort. There was a 94% and 88% probability of at least a 50% mortality relative risk reduction associated with the WB predominate strategy at 4 hours and 24 hours, respectively. CONCLUSION: Preferential transfusion of WB during the initial resuscitation demonstrated a 99% probability of being superior to component predominant resuscitations with regards to 4-hour and 24-hour mortality suggesting that WB predominant resuscitations may be superior for improving early mortality. Prospective, randomized trials should be sought. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level IV.

Postoperative warfarin following mitral valve repair or bioprosthetic valve replacement.

BACKGROUND AND AIM OF THE STUDY: Short-term postoperative warfarin therapy has been used to decrease neurologic events following mitral valve repair or bioprosthetic replacement (MVR). The study aim was to compare the short- and long-term outcomes of patients undergoing mitral valve surgery with or without short-term postoperative warfarin. METHODS: A single academic US institution retrospective review was performed on discharged patients who underwent MVR between January 1996 and March 2010. Patients were allocated to two groups: MVR with four to six weeks of postoperative warfarin (n = 315; Warfarin group) or MVR without postoperative warfarin (n = 257; No warfarin group). Patients who required either preoperative or postoperative warfarin for any disease process (e.g., atrial fibrillation, mechanical valve, deep venous thrombosis) were excluded. Logistic and Cox proportional hazards regression models were constructed to evaluate the effects of warfarin on short- and long-term outcomes, respectively. Adjusted odds ratios (AOR) and adjusted hazard ratios (AHR), with 95% confidence intervals (CI) were constructed for each outcome. To reduce selection bias, propensity scoring methods were employed to balance the groups with respect to 54 preoperative variables. RESULTS: Mean age was not significantly different between groups (No warfarin group = 56.8 +/- 14.5 years versus Warfarin group 55.9 +/- 12.9 years; p = 0.46). The average length of hospital stay was 9.8 +/- 8.4 days and 7.3 +/- 4.5 days in the No warfarin and Warfarin groups, respectively (p < 0.001). At the six-week follow up the incidences of stroke (p = 0.74), pleural effusions (p = 0.88), pericardial effusions (p = 0.75), and bleeding complications (p = 0.30) were similar between the two groups. In an unadjusted Kaplan-Meier analysis, the No warfarin group had a poorer long-term survival than the Warfarin group (p < 0.001). However, after propensity adjustment, the benefit of warfarin was not statistically significant (AHR = 0.66, 95% CI 0.40-1.08, p = 0.098). CONCLUSION: The use of postoperative warfarin following MVR does not reduce the incidence of stroke at early follow up. However, there remains a trend for improved long-term outcomes in those patients receiving postoperative warfarin therapy.

Intimate Partner Violence at a Level-1 Trauma Center During the COVID-19 Pandemic: An Interrupted Time Series Analysis.

Risks of intimate partner violence (IPV) escalated during the COVID-19 pandemic given mitigation measures, socioeconomic hardships, and isolation concerns. The objective of this study was to explore the impact of COVID-19 on the incidence of IPV. We conducted an interrupted time series analysis for IPV incidence at a single level 1 trauma center located in the United States. IPV cases were identified by triangulation of institutional data sources. There were 4,624 traumatic injuries of which 292 (6.3%) were due to IPV. IPV-related injury admissions increased 17% in the weeks following the COVID lockdown (RR = 1.17; 95% CI: 1.16, 1.19). Over a quarter of victims (27.4%) were male. Compared to before COVID, victims of IPV during the pandemic were younger (p = .04); no difference in mechanism or severity of injury was found. Our results suggest an ongoing need for universal IPV screening during health emergencies to avoid missed opportunities for IPV detection and referral to support services.

Superior Mesenteric Artery and Vein Injuries: Operative Strategies and Outcomes.

Traumatic injuries to the mesenteric vessels are rare and often lethal. Visceral vessels, such as the superior mesenteric artery (SMA) and vein (SMV), supply blood to the small and large bowel by a rich system of collaterals. Because fewer than 100 such injuries have been described in the literature, they pose challenges in both diagnosis and management and can unfortunately result in high mortality rates. Prompt diagnosis, surgical intervention, and resuscitation can lead to improved outcomes. Here, we review the literature surrounding traumatic injuries of the SMA/SMV and discuss management strategies.

Screening, Brief Intervention, and Referral to Treatment to Prevent Post-Traumatic Stress Disorder After Gunshot Wounds.

Screening, brief intervention, and referral to treatment (SBIRT) is an intervention originally developed to prevent and deter substance abuse. Adaptation of the SBIRT model to prevent post-traumatic stress disorder (PTSD) may potentially reduce acute stress symptoms after traumatic injury. We conducted a prospective randomized control study of adult patients admitted for gunshot wounds. Patients were randomized to intervention (INT) vs. treatment as usual (TAU) groups. INT received the newly developed SBIRT Intervention for Trauma Patients (SITP)-a 15-minute session with elements of cognitive behavioral therapy techniques. SITP took place during the index hospitalization; both groups had followup at 30 and 90 days at which time a validated PTSD screening tool, PCL-5, was administered. Most of the 46 participants were young (mean age = 30.5y), male (91.3%), and black (86.9%). At three-month follow-up, SBIRT and TAU patients had similar physical healing scores but the SBIRT arm showed reductions in PTSD symptoms.

Mass Casualty Shootings and Emergency Preparedness: A Multidisciplinary Approach for an Unpredictable Event.

Mass casualty events (MCE) are an infrequent occurrence to most daily healthcare systems however these incidents are the causation for new hospital preparedness and the development of coordinated emergency services. The broad support and operational plans outside the hospital include emergency medical services, local law enforcement, government agencies, and city officials. Modern-day hospital disaster preparedness goals include scheduled training for healthcare personnel to ensure effective and accurate triage for a high-volume of injured patients. This MDT collaboration strengthens the emergency response to optimize the delivery of life-saving care during MCEs. This review identifies the clinical importance of the interdisciplinary team interactions and the lessons learned from past MCE experiences, strengthening healthcare system readiness for such critical incidents.

Outcomes of off-pump aortic valve bypass surgery for the relief of aortic stenosis in adults.

BACKGROUND: Elderly patients with aortic stenosis presenting for an aortic valve replacement with a hostile ascending aorta remain a challenging patient cohort. The purpose of this study was to assess outcomes after the use of an aortic valve bypass performed without cardiopulmonary bypass. METHODS: A retrospective review was performed on 21 high-risk patients who underwent primary, isolated aortic valve bypass from September 2004 to June 2009 at Emory Healthcare Hospitals. Aortic valve bypass was used for a porcelain aorta alone in 6 (28.6%) patients, previous coronary artery bypass grafting in 4 (19.0%), or both in 10 (47.6%). One patient (4.8%) was thought not to be a candidate for cardiopulmonary bypass secondary to a severe cirrhosis. RESULTS: Mean age was 73.9±7.0 years (median, 75.0 years), and 15 patients (71.4%) were male. Mean New York Heart Association classification was 3.0±1.0 (median, 3.0), and preoperative ejection fraction was 0.460±0.163 (median, 0.500). Preoperative comorbidities included peripheral vascular disease (n=10; 47.6%), chronic lung disease (n=16; 76.2%), diabetes mellitus (n=10; 47.6%), and dialysis-dependence (n=2; 9.5%). Either an 18-mm (n=11; 52.4%) or 20-mm (n=10; 47.6%) conduit was used, with an interposed Freestyle 21 porcine root in all patients. All operations were performed without cardiopulmonary bypass. There were no intraoperative mortalities. The mean intensive care unit stay was 133.7±161.3 hours (median, 80.2 hours), and overall postoperative length of stay was 12.9±10.8 days (median, 9.0 days). In-hospital mortality occurred in 3 patients (14.3%). Mid-term follow-up shows an additional 4 patients died at a median follow-up of 1.3 years. CONCLUSIONS: Aortic valve bypass without cardiopulmonary bypass is a feasible alternative for the treatment of severe aortic stenosis with acceptable short-term morbidity and minimal mortality in this extremely high-risk surgical population.