Comparison of treatment and outcomes in blunt thoracic aortic injury based on different vascular surgery guidelines.

OBJECTIVE: Society for Vascular Surgery (SVS) recommendations for managing intimal (grade 1) blunt thoracic aortic injuries (BTAIs) include observation and medical management. University of Washington (UW) revised criteria suggest that intimal injuries with ≥1 cm flap should be upgraded to a moderate injury and treatment be considered. We sought to evaluate and compare SVS and UW criteria for BTAI and determine how discordance in grading affected treatment and outcome. METHODS: We reviewed all patients admitted with BTAI from January 1, 2011, to March 31, 2022. Data included injury grading, demographics, and concomitant traumatic injuries. Images were reviewed to categorize the injury with both grading systems. Treatment and outcomes were analyzed for concordant and discordant groups. RESULTS: Our cohort comprised 208 patients after excluding four who died upon arrival. The mean age was 45 ± 19 years, 69% were men, and the median injury severity score was 34 (interquartile range, 26-45). Strong agreement was observed between the grading systems (kappa = 0.88). All patients with concordant grade 1 injuries (n = 54) were observed. SVS grade 1/2 BTAIs were reclassified in 12 of 71 patients (16.9%). Two (28.6%) SVS grade 2 injuries were graded lower with the UW criteria; neither patient required immediate or delayed repair. Ten (15.6%) SVS grade 1 BTAIs were graded higher with UW criteria. Of these, six underwent repair (one for preoperative embolization), and four were observed without sequalae. Overall mortality was 7.7% with no difference for concordant or discordant grades (7.7% vs 8.3%; P = .99). No aneurysm-related mortalities were observed. Follow-up imaging was available for 94 survivors (49.0%) at a median of 193 days (interquartile range, 42-522 days). Two patients unrepaired at the index hospitalization (SVS grade 3/UW grade 2) underwent successful delayed repair. No patient observed for a minimal injury had BTAI progression or required treatment. CONCLUSIONS: The UW grading system may upgrade or downgrade SVS grade 1 or 2 BTAI for as many as one in six injuries. Upgraded injuries should prompt consideration of repair if there is evidence of flap progression or thromboembolic complications. Downgraded injuries suggest that treatment may not be necessary; clinical expertise is key to determine optimal management in these patients.

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.

QT interval prolongation and the rate of malignant ventricular dysrhythmia and cardiac arrest in adult poisoned patients.

INTRODUCTION: Prolongation of QTc interval, a common electrocardiographic (ECG) abnormality encountered in the toxicology patient, is reportedly associated with an increased risk of malignant ventricular dysrhythmias (MVD), such as ventricular tachycardia (VT, with and without a pulse), ventricular fibrillation (VF), and/or cardiac arrest. Quantifiable cardiac arrest risk in relation to specific QTc interval length is not known in this population. METHODS: We conducted a retrospective, observational study to assess the rate of cardiac arrest and its association with degree of QTc prolongation in a cohort of patients requiring toxicology consultation. RESULTS: 550 patients were included in our analysis (average age 36 years and 49% male). Average QTc was 453 milliseconds (ms). Overall incidence of cardiac arrest in the study cohort was 1.1% with 6 reported cases; when considering patients with QTc > 500 ms, incidence was 1.7%. Two patients with cardiac arrest experienced ventricular dysrhythmia with decompensation prior to cardiac arrest; four patients developed sudden cardiac arrest. CONCLUSIONS: The risk of malignant ventricular dysrhythmia, including cardiac arrest, is low in this poisoned patient population with an overall rate of 1.1%. Two-thirds of cardiac arrest cases occurred in patients with normal QTc intervals. When considering patients with prolonged QTc intervals, the rate of cardiac arrest remains very low at 0.8%. Considering QTc greater than 500 ms, the rate of cardiac arrest is 1.7%. Further prospective studies are required to quantify the risk of malignant ventricular dysrhythmias, including cardiac arrest, and its relation to the degree of QTc interval in poisoned patients.

Traumatic Aortic and Celiac Pseudoaneurysm with Aortocaval Fistula Managed with Endovascular Aortic Cuff Deployment and Open Hepatic Revascularization.

We present the case of a young patient who sustained a gunshot wound to the abdomen initially treated with laparotomy and repair of small bowel, splenic vein and diaphragmatic injuries. Subsequent computed tomography (CT) performed for hemodynamic instability demonstrated a pseudoaneurysm involving the aorta and proximal celiac artery, with an associated aortocaval fistula. An attempt at transperitoneal repair of these injuries was aborted due to extensive inflammatory changes in the region encountered during exposure. Subsequently, a hybrid repair was performed. This consisted of exclusion of the aortic and celiac artery pseudoaneurysm using an endovascular aortic cuff (22 × 39 mm, Cook Medical) via infrarenal aortic access, surgical ligation of the celiac artery branches, and revascularization via bypass from the infrarenal aortic access site arteriotomy to the common hepatic artery.

Porcine Lung-Derived Extracellular Matrix Hydrogel Properties Are Dependent on Pepsin Digestion Time.

Hydrogels derived from decellularized lungs are promising materials for tissue engineering in the development of clinical therapies and for modeling the lung extracellular matrix (ECM) in vitro. Characterizing and controlling the resulting physical, biochemical, mechanical, and biologic properties of decellularized ECM (dECM) after enzymatic solubilization and gelation are thus of key interest. As the role of enzymatic pepsin digestion in effecting these properties has been understudied, we investigated the digestion time-dependency on key parameters of the resulting ECM hydrogel. Using resolubilized, homogenized decellularized pig lung dECM as a model system, significant time-dependent changes in protein concentration, turbidity, and gelation potential were found to occur between the 4 and 24 h digestion time points, and plateauing with longer digestion times. These results correlated with qualitative scanning electron microscopy images and quantitative analysis of hydrogel interconnectivity and average fiber diameter. Interestingly, the time-dependent changes in the storage modulus tracked with the hydrogel interconnectivity results, while the Young's modulus values were more closely related to average fiber size at each time point. The structural and biochemical alterations correlated with significant changes in metabolic activity of several representative lung cells seeded onto the hydrogels with progressive decreases in cell viability and alterations in morphology observed in cells cultured on hydrogels produced with dECM digested for >12 and up to 72 h of digestion. These studies demonstrate that 12 h pepsin digest of pig lung dECM provides an optimal balance between desirable physical ECM hydrogel properties and effects on lung cell behaviors.

Fully automated head-twitch detection system for the study of 5-HT2A receptor pharmacology in vivo.

Head-twitch behavior (HTR) is the behavioral signature of psychedelic drugs upon stimulation of the serotonin 5-HT2A receptor (5-HT2AR) in rodents. Following the previous report of a semi-automated detection of HTR based on the dynamics of mouse's head movement, here we present a system for the identification of individual HTR events in a fully automated fashion. The validity of this fully automated HTR detection system was tested with the psychedelic drug DOI in 5-HT2AR-KO mice, and via evaluation of potential sources of false-positive and false-negative HTR events. The increased throughput in data processing achieved via automation afforded the possibility of conducting otherwise time consuming HTR time-course studies. To further assess the versatility of our system, we also explored the pharmacological interactions between 5-HT2AR and the metabotropic glutamate receptor 2 (mGluR2). Our data demonstrate the potentiation effect of the mGluR2/3 antagonist LY341495 on DOI-induced HTR, as well as the HTR-blocking effect of the mGluR2/3 agonist and antipsychotic drug in development LY404039. This fully automated system can contribute to speed up our understanding of 5-HT2AR's pharmacology and its characteristic behavioral outputs in rodents.

Electrospun Decellularized Lung Matrix Scaffold for Airway Smooth Muscle Culture.

Chronic respiratory disease affects many people worldwide with little known about the intricate mechanisms driving the pathology, making it difficult to develop novel therapies. Improving the understanding of airway smooth muscle and extracellular matrix (ECM) interactions is key to developing treatments for this leading cause of death. With currently no relevant or controllable in vivo or in vitro models to investigate cell-ECM interactions in the small airways, the development of a biomimetic in vitro model with cell attachment, signaling, and organization is needed. The goal of this study was to create a biologically and structurally relevant in vitro model of small airway smooth muscle. In order to achieve this goal, a scaffold was engineered from synthetic poly-l-lactic acid (PLLA) and decellularized pig lung ECM (PLECM). PLECM scaffolds have improved physical characteristics over synthetic scaffolds, by exhibiting a significant decrease in the elastic modulus and an increase in hydrophilicity. Histological staining and SDS-PAGE showed that essential proteins or protein fragments found in natural ECM were present after processing. Human bronchial smooth muscle cells (HBSMCs) seeded onto PLECM 3D scaffolds formed confluent layers and maintained a contractile phenotype, as demonstrated by the organized arrangement of actin filaments within the cell and expected contractile protein expression of calponin 1. HBSMCs cultured on electrospun PLECM scaffold also increased alpha-1 type 1 collagen compared to those cultured on PLLA scaffolds. In summary, this research demonstrates that a PLLA/PLECM composite electrospun mat is a promising tool to produce an in vitro model of the airway with the potential for a better understanding of bronchiole smooth muscle behavior in diseased or normal states.

Conservative fluid management prevents age-associated ventilator induced mortality.

BACKGROUND: Approximately 800 thousand patients require mechanical ventilation in the United States annually with an in-hospital mortality rate of over 30%. The majority of patients requiring mechanical ventilation are over the age of 65 and advanced age is known to increase the severity of ventilator-induced lung injury (VILI) and in-hospital mortality rates. However, the mechanisms which predispose aging ventilator patients to increased mortality rates are not fully understood. Ventilation with conservative fluid management decreases mortality rates in acute respiratory distress patients, but to date there has been no investigation of the effect of conservative fluid management on VILI and ventilator associated mortality rates. We hypothesized that age-associated increases in susceptibility and incidence of pulmonary edema strongly promote age-related increases in ventilator associated mortality. METHODS: 2month old and 20month old male C57BL6 mice were mechanically ventilated with either high tidal volume (HVT) or low tidal volume (LVT) for up to 4h with either liberal or conservative fluid support. During ventilation, lung compliance, total lung capacity, and hysteresis curves were quantified. Following ventilation, bronchoalveolar lavage fluid was analyzed for total protein content and inflammatory cell infiltration. Wet to dry ratios were used to directly measure edema in excised lungs. Lung histology was performed to quantify alveolar barrier damage/destruction. Age matched non-ventilated mice were used as controls. RESULTS: At 4h, both advanced age and HVT ventilation significantly increased markers of inflammation and injury, degraded pulmonary mechanics, and decreased survival rates. Conservative fluid support significantly diminished pulmonary edema and improved pulmonary mechanics by 1h in advanced age HVT subjects. In 4h ventilations, conservative fluid support significantly diminished pulmonary edema, improved lung mechanics, and resulted in significantly lower mortality rates in older subjects. CONCLUSION: Our study demonstrates that conservative fluid alone can attenuate the age associated increase in ventilator associated mortality.

Development and characterization of a naturally derived lung extracellular matrix hydrogel.

The complexity and rapid clearance mechanisms of lung tissue make it difficult to develop effective treatments for many chronic pathologies. We are investigating lung derived extracellular matrix (ECM) hydrogels as a novel approach for delivery of cellular therapies to the pulmonary system. The main objectives of this study include effective decellularization of porcine lung tissue, development of a hydrogel from the porcine ECM, and characterization of the material's composition, mechanical properties, and ability to support cellular growth. Our evaluation of the decellularized tissue indicated successful removal of cellular material and immunogenic remnants in the ECM. The self-assembly of the lung ECM hydrogel was rapid, reaching maximum modulus values within 3 min at 37°C. Rheological characterization showed the lung ECM hydrogel to have a concentration dependent storage modulus between 15 and 60 Pa. The purpose of this study was to evaluate our novel ECM derived hydrogel and measure its ability to support 3D culture of MSCs in vitro and in vivo delivery of MSCs. Our in vitro experiments using human mesenchymal stem cells demonstrated our novel ECM hydrogel's ability to enhance cellular attachment and viability. Our in vivo experiments demonstrated that rat MSC delivery in pre-gel solution significantly increased cell retention in the lung over 24 h in an emphysema rat model. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 1922-1935, 2016.