Endovascular Management of A Symptomatic Giant Hepatic Artery Aneurysm.

Hepatic artery aneurysms (HAAs) are an uncommon clinical condition. Ruptured hepatic artery aneurysm carries a high incidence of mortality. Traditionally, they are treated with open surgical resection; however, endovascular aneurysm exclusion is an alternative option to open repair in select patients who have suitable anatomy. Here, we present a case of a giant hepatic artery aneurysm treated with a covered stent placement.

Endovascular Repair of Traumatic Infrarenal Aortic Injury in an 8-Year-Old.

The patient is an 8 year-old male presenting to outside facility following high-speed motor vehicle collision in which he was a restrained passenger. CT imaging at that time demonstrated a traumatic infrarenal aortic pseudoaneurysm, extensive pneumoperitoneum and free fluid, and an unstable L2 vertebral body fracture. He underwent exploratory laparotomy with small bowel resection prior to transfer. The patient was left in discontinuity and temporary closed. Vascular surgery was consulted upon arrival to tertiary care children's hospital. The decision was made to proceed with emergent endovascular repair. An aortogram confirmed the location of the aortic disruption well below the renal arteries, superior to the bifurcation. An 11 mm × 5 cm Viabahn covered stent was placed across the injury with adequate proximal and distal seal. This is a case of seatbelt-related pediatric infrarenal aortic injury in the setting of polytrauma. Endovascular repair was pursued in this damage-control setting.

Endovascular Repair of Transected Axillary Artery via Snare Assisted Through and Through Femoral to Brachial Artery Access.

Axillary artery injury is a rare but complex surgical problem that often requires challenging exposures, lengthy operations, and morbid outcomes for repair. For these reasons, endovascular repair is an attractive alternative as it obviates many of the challenges present with open repair. While pseudoaneurysms, dissections, and short segment injuries with limited arterial disruption are regularly treated endovascularly, complete arterial transections are almost exclusively treated with open repair as obtaining wire access across the site of injury is often not possible. Here we report a case of successful endovascular repair of a completely transected axillary artery with the use of snare assistance to obtain through and through femoral to brachial artery access. This ultimately allowed for covered stent deployment across the axillary transection restoring distal blood flow. Snare assistance in obtaining through and through access across areas of complete transection can allow for increased use of endovascular repair.

A Review of "Options in Management of Trauma to the Esophagus" (1982) "Submitted for the Literary Festschrift in Honor of J. David Richardson, MD".

This article is an update of a paper which Dave Richardson and I published in 1982, and serves as both an update of management of esophageal injuries and as a lasting tribute to my mentor and hero J. David Richardson.

Comparative Efficacy of Bilateral Thoracoscopic Splanchnicectomy for Intractable Pain Secondary to Pancreatic Cancer vs Chronic Pancreatitis.

BACKGROUND: Splanchnicectomy has been evaluated for treatment of chronic pain in both pancreatic cancer and chronic pancreatitis patients, although its efficacy has not been compared in these 2 patient populations. This study aimed to compare bilateral thoracoscopic splanchnicectomy in treatment of abdominal pain secondary with pancreatic cancer and chronic pancreatitis. STUDY DESIGN: A University of Louisville database was evaluated from July 1998 to March 2016 for patients undergoing bilateral thoracoscopic splanchnicectomy for intractable pain secondary to pancreatic cancer (n = 48) or chronic pancreatitis (n = 75). Patients were evaluated pre- and postoperatively with regard to abdominal pain and related symptoms, narcotic analgesic requirements, and hospital admissions. Narcotic use was quantified using the Kentucky All Schedule Prescription Electronic Reporting system. RESULTS: After bilateral thoracoscopic splanchnicectomy, 28% of pancreatic cancer patients continued to experience abdominal pain compared with 57% of chronic pancreatitis patients. Daily narcotic dose decreased for 74% of pancreatic cancer compared with 32% of chronic pancreatitis patients (p < 0.001). Sixty-seven percent of pancreatic cancer patients discontinued pain medications completely compared with 14% of chronic pancreatitis patients (p < 0.001). Hospitalizations decreased significantly in both groups (p < 0.001; p = 0.001), although mean number of postoperative hospitalizations was lower for pancreatic cancer (0.5) compared with chronic pancreatitis patients (2.80) (p < 0.001). Mean follow-up was significantly shorter for pancreatic cancer patients than for chronic pancreatitis patients (8 months vs 32 months; p < 0.001). CONCLUSIONS: Bilateral thoracoscopic splanchnicectomy safely, effectively, and durably relieves abdominal pain in patients with both pancreatic cancer and chronic pancreatitis. However, it is more effective in providing pain relief and preventing pain-related hospitalizations in patients with pancreatic cancer compared with those with chronic pancreatitis.

Cholinergic signaling in the gut: a novel mechanism of barrier protection through activation of enteric glia cells.

BACKGROUND: Enteric glia cells (EGCs) play an important role in maintaining proper intestinal barrier function. We have shown that vagal nerve stimulation (VNS) increases EGC activation, which is associated with better gut barrier integrity. Enteric neurons communicate with EGCs through nicotinic cholinergic signaling, which may represent a pathway by which VNS activates EGCs. This study sought to define further the mechanism by which VNS prevents intestinal barrier failure using an in vitro model. We hypothesized that a nicotinic cholinergic agonist would increase EGC activation, prevent intestinal nuclear factor kappa-B (NF-κB) activation, and result in better intestinal barrier function. METHODS: Cultured EGCs were exposed to the nicotinic cholinergic agonist nicotine. Expression of glial fibrillary acidic protein (GFAP) was measured by immunoblot to determine changes in EGC activation. Caco-2 cells were grown to confluence and incubated alone or in co-culture with EGCs. Cells were then stimulated with Cytomix for 24 h in the presence or absence of nicotine, and barrier integrity was assessed by permeability to 4-kDa FITC-dextran. Changes in phosphorylated inhibitor of NF-κb (P-IκBα) and phosphorylated NF-κB (P-NF-κB) were assessed by immunoblot. RESULTS: Stimulation with nicotine resulted in EGC activation, as demonstrated by an increase in GFAP expression. Cytomix stimulation increased permeability in Caco-2 cells cultured alone or with EGCs. Treatment of stimulated Caco-2/EGC co-cultures with nicotine reduced permeability similar to control. Nicotine failed to prevent barrier permeability in Caco-2 cells alone. Co-culture of stimulated Caco-2 cells with nicotine-activated EGCs prevented Cytomix-induced increases in P-IκBα and P-NF-κB expression. CONCLUSION: A pharmacologic nicotinic cholinergic agonist increased EGC activation and improved intestinal epithelial barrier function in an in vitro model of intestinal injury. Nicotine-activated EGCs appear to modulate barrier function by preventing the activation of the NF-κB pathway. Therapies aimed at activating EGCs may have important clinical applications for improving intestinal barrier function after injury.

Enteric glia cells attenuate cytomix-induced intestinal epithelial barrier breakdown.

BACKGROUND: Intestinal barrier failure may lead to systemic inflammation and distant organ injury in patients following severe injury. Enteric glia cells (EGCs) have been shown to play an important role in maintaining gut barrier integrity through secretion of S-Nitrosoglutathione (GSNO). We have recently shown than Vagal Nerve Stimulation (VNS) increases EGC activation, which was associated with improved gut barrier integrity. Thus, we sought to further study the mechanism by which EGCs prevent intestinal barrier breakdown utilizing an in vitro model. We postulated that EGCs, through the secretion of GSNO, would improve intestinal barrier function through improved expression and localization of intestinal tight junction proteins. METHODS: Epithelial cells were co-cultured with EGCs or incubated with GSNO and exposed to Cytomix (TNF-α, INF-γ, IL-1ß) for 24 hours. Barrier function was assessed by permeability to 4kDa FITC-Dextran. Changes in tight junction proteins ZO-1, occludin, and phospho-MLC (P-MLC) were assessed by immunohistochemistry and immunoblot. KEY RESULTS: Co-culture of Cytomix-stimulated epithelial monolayers with EGCs prevented increases in permeability and improved expression and localization of occludin, ZO-1, and P-MLC. Further, treatment of epithelial monolayers with GSNO also prevented Cytomix-induced increases in permeability and exhibited a similar improvement in expression and localization of occludin, ZO-1, and P-MLC. CONCLUSIONS & INFERENCES: The addition of EGCs, or their secreted mediator GSNO, prevents epithelial barrier failure after injury and improved expression of tight junction proteins. Thus, therapies that increase EGC activation, such as VNS, may be a novel strategy to limit barrier failure in patients following severe injury.

Uncovering the neuroenteric-pulmonary axis: vagal nerve stimulation prevents acute lung injury following hemorrhagic shock.

AIMS: Trauma/hemorrhagic shock (T/HS) induced gut injury is known to initiate a systemic inflammatory response which can lead to secondary lung injury. We have shown that vagal nerve stimulation (VNS) protects intestinal epithelial integrity after a severe burn insult. We hypothesize that VNS will protect the lung from injury following T/HS by preventing intestinal barrier failure. MAIN METHODS: Male Balb/c mice were subjected to a T/HS model with and without cervical VNS. Intestinal injury was evaluated by measuring changes in gut barrier function and tight junction protein localization. Lung injury was evaluated using histology and markers of lung inflammation. Using NF-kB-luciferase (NF-kB-luc) transgenic mice, NF-kb-DNA binding was measured by photon emission analysis at 4 after injury. KEY FINDINGS: T/HS is associated gut injury characterized by histologic injury, increased epithelial permeability, and altered localization of gut tight junction proteins. Cervical VNS prevented the T/HS-induced changes in gut barrier integrity. Gut injury after T/HS was associated with acute lung injury at 24 h characterized by histologic injury, increased number of MPO positive stained cells and MPO enzymatic activity, and increased ICAM-1 expression in lung endothelium. VNS decreased T/HS-induced lung injury with a marked decrease in lung inflammation compared to T/HS alone. Lungs harvested from NF-kB-luc mice at 4h post VNS+T/HS demonstrated decreased DNA binding of NF-kB compared to T/HS alone as measured by changes in bioluminescence. SIGNIFICANCE: VNS is effective in protecting against acute lung injury caused by hemorrhagic shock through its ability to prevent gut barrier dysfunction.

Targeting α-7 nicotinic acetylcholine receptor in the enteric nervous system: a cholinergic agonist prevents gut barrier failure after severe burn injury.

We have previously shown that vagal nerve stimulation prevents intestinal barrier loss in a model of severe burn injury in which injury was associated with decreased expression and altered localization of intestinal tight junction proteins. α-7 Nicotinic acetylcholine receptor (α-7 nAchR) has been shown to be necessary for the vagus nerve to modulate the systemic inflammatory response, but the role of α-7 nAchR in mediating gut protection remained unknown. We hypothesized that α-7 nAchR would be present in the gastrointestinal tract and that treatment with a pharmacological agonist of α-7 nAchR would protect against burn-induced gut barrier injury. The effects of a pharmacological cholinergic agonist on gut barrier integrity were studied using an intraperitoneal injection of nicotine 30 minutes after injury. Intestinal barrier integrity was examined by measuring permeability to 4-kDa fluorescein isothiocyanate-dextran and by examining changes in expression and localization of the intestinal tight junction proteins occludin and ZO-1. Nicotine injection after injury prevented burn-induced intestinal permeability and limited histological gut injury. Treatment with nicotine prevented decreased expression and altered localization of occludin and ZO-1, as seen in animals undergoing burn alone. Defining the interactions among the vagus nerve, the enteric nervous system, and the intestinal epithelium may lead to development of targeted therapeutics aimed at reducing gut barrier failure and intestinal inflammation after severe injury.

CPSI-121 pharmacologically prevents intestinal barrier dysfunction after cutaneous burn through a vagus nerve-dependent mechanism.

BACKGROUND: We have recently demonstrated the protective effects of electrical stimulation of the vagus nerve in prevention of gut injury after severe burn. Here we evaluate the potential for a pharmacologic agonist of the vagus nerve as an approach to regulate outcomes in preclinical models. We tested a new generation of guanylhydrazone-derived compounds, CPSI-121; a compound that may activate the parasympathetic nervous system through poorly understood mechanisms to determine whether we could prevent intestinal mucosal barrier breakdown. METHODS: Male balb/c mice were subjected to a full-thickness, 30% total body surface area steam burn, and the efficacy of CPSI-121 was tested against vagus nerve stimulation (VNS) postburn at 4 hours. Surgical vagotomy was used to disrupt the neuroenteric axis and gut injury prevention was assessed. Gut barrier dysfunction was quantified by permeability to 4-kDa fluorescein isothiocyanate-dextran. Gut injury was assessed by histologic evaluation. Tight junction protein expression (ZO-1 and occludin) was characterized by immunofluorescence and immunoblot. RESULTS: VNS and CPSI-121 administration significantly reduced the permeability to 4-kDa fluorescein isothiocyanate-dextran and maintained normal histology compared with burn. However, abdominal vagotomy eliminated the protective effects of both VNS and CPSI-121. ZO-1 and occludin expression was similar to sham in VNS and CPSI-121-treated burn animals, but significantly altered in burn-vagotomized animals. Splenectomy did not alter the effect of CPSI-121. CONCLUSION: Similar to direct electrical VNS, CPSI-121 effectively protects the intestinal mucosal barrier from breakdown after severe burn. We suggest that this could represent a noninvasive therapy to prevent end-organ dysfunction after trauma that would be administered during resuscitation.

Efferent vagal nerve stimulation attenuates acute lung injury following burn: The importance of the gut-lung axis.

BACKGROUND: The purpose of this study was to assess acute lung injury when protection to the gut mucosal barrier offered by vagus nerve stimulation is eliminated by an abdominal vagotomy. METHODS: Male balb/c mice were subjected to 30% total body surface area steam burn with and without electrical stimulation to the right cervical vagus nerve. A cohort of animals were subjected to abdominal vagotomy. Lung histology, myeloperoxidase and ICAM-1 immune staining, myeloperoxidase enzymatic assay, and tissue KC levels were analyzed 24 hours after burn. Additionally, lung IkB-α, NF-kB immunoblots, and NF-kB-DNA binding measured by photon emission analysis using NF-kB-luc transgenic mice were performed. RESULTS: Six hours post burn, phosphorylation of both NF-kB p65 and IkB-α were observed. Increased photon emission signal was seen in the lungs of NF-kB-luc transgenic animals. Vagal nerve stimulation blunted NF-kB activation similar to sham animals whereas abdominal vagotomy eliminated the anti-inflammatory effect. After burn, MPO positive cells and ICAM-1 expression in the lung endothelium was increased, and lung histology demonstrated significant injury at 24 hours. Vagal nerve stimulation markedly decreased neutrophil infiltration as demonstrated by MPO immune staining and enzyme activity. Vagal stimulation also markedly attenuated acute lung injury at 24 hours. The protective effects of vagal nerve stimulation were reversed by performing an abdominal vagotomy. CONCLUSION: Vagal nerve stimulation is an effective strategy to protect against acute lung injury following burn. Moreover, the protective effects of vagal nerve stimulation in the prevention of acute lung injury are eliminated by performing an abdominal vagotomy. These results establish the importance of the gut-lung axis after burn in the genesis of acute lung injury.

Burn-induced acute lung injury requires a functional Toll-like receptor 4.

The role of the Toll-like receptor 4 (TLR4), a component of the innate immune system, in the development of burn-induced acute lung injury (ALI) has not been completely defined. Recent data suggested that an intact TLR4 plays a major role in the development of organ injury in sterile inflammation. We hypothesized that burn-induced ALI is a TLR4-dependent process. Male C57BL/6J (TLR4 wild-type [WT]) and C57BL/10ScN (TLR4 knockout [KO]) mice were subjected to a 30% total body surface area steam burn. Animals were killed at 6 and 24 h after the insult. Lung specimens were harvested for histological examination after hematoxylin-eosin staining. In addition, lung myeloperoxidase (MPO) and intercellular adhesion molecule 1 immunostaining was performed. Lung MPO was measured by an enzymatic assay. Total lung keratinocyte-derived chemoattractant (IL-8) content was measured by enzyme-linked immunosorbent assay. Western blot was performed to quantify phosphorylated IκBα, phosphorylated nuclear factor κB p65 (NF-κBp65), and high mobility group box 1 expression. Acute lung injury, characterized by thickening of the alveolar-capillary membrane, hyaline membrane formation, intraalveolar hemorrhage, and neutrophil infiltration, was seen in WT but not KO animals at 24 h. Myeloperoxidase and intercellular adhesion molecule 1 immunostaining of KO animals was also similar to sham but elevated in WT animals. In addition, a reduction in MPO enzymatic activity was observed in KO mice as well as a reduction in IL-8 levels compared with their WT counterparts. Burn-induced ALI develops within 24 h after the initial thermal insult in our model. Toll-like receptor 4 KO animals were clearly protected and had a much less severe lung injury. Our data suggest that burn-induced ALI is a TLR4-dependent process.