Search

Introduction: Academic Medical Centers ("AMCs") have served as a hub of the United States ("US") health system and represented the state-of-the art in American health care for well over a century. Currently, the global healthcare market is both massive and expanding and is being altered by the unprecedented impact of technological advances and globalization. This provides AMCs a platform to enter into trans-national collaborative partnerships with healthcare organizations around the world, thus providing a means to deliver on its promise globally while also expanding and diversifying its resources. A number of leading US AMCs have engaged in global collaborative healthcare, employing different models based on services offered, global distribution, and inclination to assume risk. Engaging in these collaborations requires significant effort from across the health system, and an understanding of the resources required is paramount for effective delivery and to avoid overextension and diversion from the primary mission of these organizations. The goal of this paper is to discuss the role of US AMCs in this current global healthcare landscape and to also investigate our institutional faculty and staff resource requirements to support the operating model., Methodology: We extracted and retrospectively analyzed data from the JHI Global Services database for a 3-year period (Jan, 2013-Dec, 2015) to determine total utilization (hours and full time equivalent (FTE)), utilization by profession, and clinical and non-clinical areas of expertise., Results: JHI utilized on average 21,940 h annually, or 10.55 FTEs of faculty and staff subject matter experts. The majority of the hours are for work performed by physician faculty members from 23 departments within the School of Medicine, representing 77% percent or on average 16,894 h annually. Clinical and allied health departments had an average annual utilization of 17,642 h or 7.8 FTEs, while non-clinical departments, schools and institutes averaged 4298 h or 1.9 FTEs, representing 80.4% and 19.6% respectively., Conclusion: We found that significant human resources are required within a broad range of AMC subject matter expertise across multiple disciplines, and that with adequate forecasting AMCs can successfully engage in these collaborations while continuing to fulfill their core mission.

Despite advancements in renal replacement therapy, the mortality rate for acute kidney injury (AKI) remains unacceptably high, likely due to remote organ injury. Kidney ischemia-reperfusion injury (IRI) activates cellular and soluble mediators that incite a distinct pulmonary proinflammatory and proapoptotic response. Tumor necrosis factor receptor 1 (TNFR1) has been identified as a prominent death receptor activated in the lungs during ischemic AKI. We hypothesized that circulating TNF-α released from the postischemic kidney induces TNFR1-mediated pulmonary apoptosis, and we aimed to elucidate molecular pathways to programmed cell death. Using an established murine model of kidney IRI, we characterized the time course for increased circulatory and pulmonary TNF-α levels and measured concurrent upregulation of pulmonary TNFR1 expression. We then identified TNFR1-dependent pulmonary apoptosis after ischemic AKI using TNFR1-/- mice. Subsequent TNF-α signaling disruption with Etanercept implicated circulatory TNF-α as a key soluble mediator of pulmonary apoptosis and lung microvascular barrier dysfunction during ischemic AKI. We further elucidated pathways of TNFR1-mediated apoptosis with NF-κB (Complex I) and caspase-8 (Complex II) expression and discovered that TNFR1 proapoptotic signaling induces NF-κB activation. Additionally, inhibition of NF-κB (Complex I) resulted in a proapoptotic phenotype, lung barrier leak, and altered cellular flice inhibitory protein signaling independent of caspase-8 (Complex II) activation. Ischemic AKI activates soluble TNF-α and induces TNFR1-dependent pulmonary apoptosis through augmentation of the prosurvival and proapoptotic TNFR1 signaling pathway. Kidney-lung crosstalk after ischemic AKI represents a complex pathological process, yet focusing on specific biological pathways may yield potential future therapeutic targets.

Kidney ischemia-reperfusion injury (IRI) activates cellular and soluble mediators that drive lung inflammatory cascades, tumor necrosis factor receptor 1 (TNFR1)-mediated programmed cell death, and microvascular barrier dysfunction, leading to acute lung injury. We hypothesized that lung microvascular endothelial cells (ECs), with their integral role in maintaining the lung-semipermeable barrier, were key cellular targets of TNFR1-mediated apoptosis during ischemic AKI. Male C57/BL6 mice and Sprague-Dawley rats underwent 60 min of bilateral renal pedicle occlusion (IRI) or sham laparotomy (sham) and were killed at 4 or 24 h. Colocalization with TUNEL, DAPI, and CD34 was performed to identify EC-specific apoptosis. Mouse ECs (CD45/CD31) isolated with novel tissue digestion techniques and magnetic microbead sorting underwent quantitative real-time polymerase chain reaction SuperArray analysis with 84 apoptosis-related genes. In parallel, rat lung microvascular ECs grown to confluence were treated with serum from rats obtained following sham or kidney IRI. Rat lung microvascular ECs treated +/- etanercept, a TNF-α/TNFR1 signaling inhibitor, underwent custom real-time polymerase chain reaction analysis for proapoptotic and TNF superfamily transcriptional events, and apoptosis was identified with caspase 3 and poly(ADP-ribose) polymerase activity assays. In vivo, TUNEL-positive cells colocalized with CD34 in whole-lung tissue and isolated lung ECs demonstrated a proapoptotic transcriptome during ischemic AKI. In vitro, ischemic AKI incited proapoptotic (FasL, Dapk1, Bcl10) and TNF superfamily (TNFR1, TNFR2, TNF-α) gene activation and increased caspase 3 and poly(ADP-ribose) polymerase activity at 24 h versus sham. Compared with vehicle, treatment of rat lung microvascular ECs with etanercept inhibited proinflammatory gene activation (E-selectin, intercellular adhesion molecule 1, interleukin 6, RhoB) and apoptosis during ischemic AKI. Ischemic AKI drives distinct proinflammatory and proapoptotic changes in the pulmonary EC transcriptome with TNFR1-dependent caspase activation and programmed cell death. Further investigation of potential EC mechanisms of kidney-lung crosstalk during AKI may identify potential therapeutic targets for this deadly disease.

Sclerosing mediastinitis is a rare, progressive condition characterized by extensive fibrotic reaction. We report the first known case of symptomatic, extrinsic compression of the carotid artery by fibrotic extension of sclerosing mediastinitis. A 54-year-old woman began experiencing neurologic symptoms from extension of a known mediastinal mass resulting in 70% to 79% stenosis of the right internal carotid artery. The stenosis was treated with endovascular stenting. Completion angiogram revealed a good result with <10% residual stenosis. At 18-month follow-up, the patient was symptom free without evidence of re-stenosis. Endovascular therapy provides a novel and durable solution in the midterm to this very rare problem., (Copyright © 2012 Society for Vascular Surgery. Published by Mosby, Inc. All rights reserved.)

Acute kidney injury (AKI) is a common complication during inpatient hospitalization, and clinical outcomes remain poor despite advancements in renal replacement therapy. AKI in the setting of multiple organ failure (MOF) remains a formidable challenge to clinicians and incurs an unacceptably high mortality rate. Kidney ischemia-reperfusion injury (IRI) incites a proinflammatory cascade and releases cellular and soluble mediators with systemic implications for remote organ injury. Evidence from preclinical models cites mechanisms of organ crosstalk during ischemic AKI including the expression of cellular adhesion molecules, lymphocyte trafficking, release of proinflammatory cytokines and chemokines, and modification of the host innate and adaptive immune response systems. In this paper, the influence of kidney IRI on systemic inflammation and distant organ injury will be examined. Recent experimental data and evolving concepts of organ crosstalk during ischemic AKI will also be discussed in detail.

Acute kidney injury (AKI) leads to increased lung microvascular permeability, leukocyte infiltration, and upregulation of soluble inflammatory proteins in rodents. Most work investigating connections between AKI and pulmonary dysfunction, however, has focused on characterizing whole lung tissue changes associated with AKI. Studies at the cellular level are essential to understanding the molecular basis of lung changes during AKI. Given that the pulmonary microvascular barrier is functionally abnormal during AKI, we hypothesized that AKI induces a specific proinflammatory and proapoptotic lung endothelial cell (EC) response. Four and 24 h after kidney ischemia/reperfusion injury or bilateral nephrectomy, murine pulmonary ECs were isolated via tissue digestion followed by magnetic bead sorting. Purified lung ECs were analyzed for changes in mRNA expression using real-time SuperArray polymerase chain reaction analysis of genes related to EC function. In parallel experiments, confluent rat pulmonary microvascular ECs were treated with AKI or control serum to evaluate functional cellular alterations. Immunocytochemistry and FACS analysis of Annexin V/propidium iodide staining were used to evaluate cytoskeletal changes and promotion of apoptosis. Isolated murine pulmonary ECs exhibited significant changes in the expression of gene products related to inflammation, vascular reactivity, and programmed cell death. Further experiments using an in vitro rat pulmonary microvascular EC system revealed that AKI serum induced functional cellular changes related to apoptosis, including structural actin alterations and phosphatidylserine translocation. Analysis and segregation of both upregulated and downregulated genes into functional roles suggest that these transcriptional events likely participate in the transition to an activated proinflammatory and proapoptotic EC phenotype during AKI. Further mechanistic analysis of EC-specific events in the lung during AKI might reveal potential novel therapeutic targets for the deleterious kidney-lung crosstalk in the critically ill patient.

Management of acute pathology remains one of the most challenging clinical entities, with a persistently high mortality rate both prior to and upon arrival to a hospital. Responding to the distinct advantages of endovascular approaches to aortic disease, many high-volume cardiovascular centers have focused on endovascular therapies for managing patients with ruptured or leaking aortic aneurysms and other acute aortic syndromes. Nonetheless, similar to outcomes for other surgical emergencies, time and efficiency are critical in managing these conditions. Early diagnosis, transport to an appropriate acute care facility, rapid institution of optimal medical management, availability of cardiovascular anesthesia and intensive care, and appropriate and timely surgical intervention continue to be the keys to success. This article discusses the endovascular approach to ruptured abdominal and thoracic aortic aneurysms.

Introduction: Mesenteric ischemia-reperfusion injury (IRI) leads to systemic inflammation and multiple organ failure in clinical and laboratory settings. We investigated the lung structural, functional, and genomic response to mesenteric IRI with and without regional intraischemic hypothermia (RIH) in rodents and hypothesized that RIH would protect the lung and preferentially modulate the distant organ transcriptome under these conditions., Methods: Sprague-Dawley rats underwent sham laparotomy or superior mesenteric artery occlusion (SMAO) for 60 minutes with or without RIH. Gut temperature was maintained at 15°-20°C during SMAO, and systemic normothermia (37°C) was maintained throughout the study period. At 6 or 24 hours, lung tissue was collected for (1) histology, (2) myeloperoxidase activity, (3) bronchoalveolar lavage (BAL) fluid protein concentrations, (4) lung wet/dry ratios, and (5) total RNA isolation and hybridization to Illumina's Sentrix BeadChips (>22,000 probes) for gene expression profiling. Significantly affected genes (false discovery rate <5% and fold change ≥1.5) were linked to gene ontology (GO) terms using MAPPFinder, and hypothermia-suppressed genes were further analyzed with Pubmatrix., Results: Mesenteric IRI-induced lung injury, as evidenced by leukocyte trafficking, alveolar hemorrhage, and increased BAL protein and wet/dry ratios, and activated a proinflammatory lung transcriptome compared with sham. In contrast, rats treated with RIH exhibited lung histology, BAL protein, and wet/dry ratios similar to sham. At 6 hours, GO analysis identified 232 hypothermia-suppressed genes related to inflammation, innate immune response, and cell adhesion, and 33 hypothermia-activated genes related to lipid and amine metabolism and defense response. Quantitative real-time polymerase chain reaction validated select array changes in top hypothermia-suppressed genes lipocalin-2 (lcn-2) and chemokine ligand 1 (CXCL-1), prominent genes associated with neutrophil activation and trafficking., Conclusions: Therapeutic hypothermia during SMAO provides distant organ protection and preferentially modulates the IRI-activated transcriptome in the rat lung. This study identifies potential novel diagnostic and therapeutic targets of mesenteric IRI and provides a platform for further mechanistic study of hypothermic protection at the cellular and subcellular level., (Copyright © 2010 Society for Vascular Surgery. Published by Mosby, Inc. All rights reserved.)

Distant organ effects of acute kidney injury (AKI) are a leading cause of morbidity and mortality. While little is known about the underlying mechanisms, limited data suggest a role for inflammation and apoptosis. Utilizing a lung candidate gene discovery approach in a mouse model of ischemic AKI-induced lung dysfunction, we identified prominent lung activation of 66 apoptosis-related genes at 6 and/or 36 h following ischemia, of which 6 genes represent the tumor necrosis factor receptor (TNFR) superfamily, and another 23 genes are associated with the TNFR pathway. Given that pulmonary apoptosis is an important pathogenic mechanism of acute lung injury (ALI), we hypothesized that AKI leads to pulmonary proapoptotic pathways that facilitate lung injury and inflammation. Functional correlation with 1) terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling and 2) active caspase-3 (aC3) activity, immunoblotting, and immunohistochemistry (IHC) identified kidney IRI-induced pulmonary apoptosis at 24 h, and colocalization studies with CD34 identified predominantly endothelial apoptosis. Mice were treated with the caspase inhibitor Z-VAD-FMK (0.25 mg ip) or vehicle 1 h before and 8 h after sham or kidney IRI, and bronchoalveolar lavage fluid protein was measured at 36 h as a surrogate for lung leak. Caspase inhibition reduced lung microvascular changes after kidney IRI. The pulmonary apoptosis seen in wild-type control mice during AKI was absent in TNFR(-/-) mice. Using an initial genomic approach to discovery followed by a mechanistic approach to disease targeting, we demonstrate that pulmonary endothelial apoptosis is a direct mediator of the distant organ dysfunction during experimental AKI.

It is well-established that significant ischemia-reperfusion injury during kidney transplantation results in increased incidence of long-term fibrosis and rejection. To test for a role of T cell infiltration and activation following ischemic injury, we induced both bilateral and unilateral renal ischemia in mice, followed by reperfusion, and then isolated mononuclear cells. Analysis of these cells by flow cytometry showed that 2 weeks after bilateral ischemia there was a significant increase of CD8(+) T cells. Furthermore, both CD4(+) and CD8(+) T cells infiltrated the injured kidney 6 weeks after unilateral ischemia. These T cells had increased expression of CD69(+) and CD44(hi)CD62L(-), markers of activation and effector-memory, respectively. CD4(+)NK1.1(+) and CD19(+) B cells were decreased in percentage both 6 and 11 weeks after bilateral or unilateral injury. There was a significant upregulation of IL-1beta, IL-6, TNF-alpha, IFN-gamma, MIP-2, and RANTES expression, measured by real-time PCR, 6 weeks after unilateral renal ischemia, further indicating T cell activation. Depletion of CD4(+) and CD8(+) T cells before ischemia caused less medullary damage and reduced kidney IFN-gamma expression, whereas their depletion following ischemia increased kidney IL-1beta; however, depletion of these cells had no effect on histological damage to the kidney. Our study demonstrates that moderate or severe kidney ischemia induces long-term T lymphocyte infiltration and cytokine/chemokine upregulation, leading to kidney structural changes.

We hypothesized that the influence of acute kidney injury (AKI) on the sensitivity of the lung to an injurious process varies with the severity of the injurious process. Thus, we thought that AKI would exacerbate lung injury from low degrees of lung trauma but attenuate lung injury from higher degrees of lung trauma. C57BL/6 mice underwent AKI (30-min kidney ischemia) or sham surgery, followed at 24 h by 4 h of spontaneous breathing (SB), mechanical ventilation with low tidal volume (7 ml/kg, LTV), or mechanical ventilation with high tidal volume (30 ml/kg, HTV). Compared with LTV, median bronchoalveolar lavage (BAL) protein leak was significantly lower with SB and greater with HTV in both sham and AKI mice. Compared with LTV, median Evans blue dye-labeled albumin extravasation in lungs (L-EBD) was also significantly lower with SB and greater with HTV. L-EBD showed a significant interaction between ventilatory mode and kidney health, such that AKI attenuated the L-EBD rise seen in HTV vs. LTV sham mice. An interaction between ventilatory mode and kidney health could also be seen in BAL neutrophil number (PMN). Thus, AKI attenuated the BAL PMN rise seen in HTV vs. LTV sham mice. These data support the presence of a complex interaction between mechanical ventilation and AKI in which the sensitivity of the lung to trauma varies with the magnitude of the trauma and may involve a modification of pulmonary neutrophil activity by AKI.

Studies in humans and animal models have demonstrated that acute kidney injury (AKI) has a significant effect on the function of extrarenal organs. The combination of AKI and lung dysfunction is associated with 80% mortality; the lung, because of its extensive capillary network, is a prime target for AKI-induced effects. The study presented here tested the hypothesis that AKI leads to a vigorous inflammatory response and produces distinct genomic signatures in the kidney and lung. In a murine model of ischemic AKI, prominent global transcriptomic changes and histologic injury in both kidney and lung tissues were identified. These changes were evident at both early (6 h) and late (36 h) timepoints after 60-min bilateral kidney ischemia and were more prominent than similar timepoints after sham surgery or 30 min of ischemia. The inflammatory transcriptome (109 genes) of both organs changed with marked similarity, including the innate immunity genes Cd14, Socs3, Saa3, Lcn2, and Il1r2. Functional genomic analysis of these genes suggested that IL-10 and IL-6 signaling was involved in the distant effects of local inflammation, and this was supported by increased serum levels of IL-10 and IL-6 after ischemia-reperfusion. In summary, this is the first comprehensive analysis of concomitant inflammation-associated transcriptional changes in the kidney and a remote organ during AKI. Functional genomic analysis identified potential mediators that connect local and systemic inflammation, suggesting that this type of analysis may be a useful discovery tool for novel biomarkers and therapeutic drug development.

Acute kidney injury (AKI) is associated with significant mortality, which increases further when combined with acute lung injury. Experiments in rodents have shown that kidney ischemia-reperfusion injury (IRI) facilitates lung injury and inflammation. To identify potential ischemia-specific lung molecular pathways involved, we conducted global gene expression profiling of lung 6 or 36 h following 1) bilateral kidney IRI, 2) bilateral nephrectomy (BNx), and 3) sham laparotomy in C57BL/6J mice. Bronchoalveolar lavage fluid analysis revealed increased total protein, and lung histology revealed increased cellular inflammation following IRI, but not BNx, compared with sham controls. Total RNA from whole lung was isolated and hybridized to 430MOEA (22,626 genes) GeneChips (n = 3/group), which were analyzed by robust multichip average and significance analysis of microarrays and linked to gene ontology (GO) terms using MAPPFinder. The microarray power analysis predicted that the false discovery rate (q < 1%) and > or =50%-fold change compared with sham would represent significant changes in gene expression. Analysis identified 266 and 455 ischemia-specific, AKI-associated lung genes with increased expression and 615 and 204 with decreased expression at 6 and 36 h, respectively, compared with sham controls. Real-time PCR analysis validated select array changes in lung serum amyloid A3 and endothelin-1. GO analysis revealed significant activation (Z > 1.95) of several proinflammatory and proapoptotic biological processes. Ischemic AKI induces functional and transcriptional changes in the lung distinct from those induced by uremia alone. Further investigation using this lung molecular signature induced by kidney IRI will provide mechanistic insights and new therapies for critically ill patients with AKI.

Background: Endovascular repair has emerged as a less-invasive treatment for descending thoracic aortic (DTA) aneurysms. However, the durability of this procedure relies on the stability of proximal and distal fixation sites. This study analyzes 3 years of computed tomography (CT) data on aortic neck morphology after endovascular DTA aneurysm repair., Methods: Between 1999 and 2001, 139 patients underwent successful endovascular DTA repair as part of a prospective, multicenter clinical trial investigating the Gore TAG thoracic endoprosthesis. Contrast-enhanced, high-resolution CT scans were obtained at 1 (baseline), 12, 24, and 36 months and submitted to an independent core laboratory for image analysis. The aorta was carefully measured by using computerized planimetry and a standardized protocol. Neck diameter was measured at 10-mm intervals for 2 cm above and below the aneurysm and correlated with graft migration and endoleak., Results: The mean proximal neck diameter increased from a baseline of 30.2 +/- 4.6 mm to 32.0 +/- 4.3 mm at 36 months (P <.05), and the annual diameter increase was 0.8, 0.4, and 0.6 mm at 12, 24, and 36 months. The mean distal neck diameter increased from 29.4 +/- 3.8 mm to 32.1 +/- 5.0 mm at 36 months (P <.05), and the annual diameter increase was 1.1, 0.4, and 1.2 mm at 12, 24, and 36 months. At 36 months, freedom from neck dilation of > or =5 mm was 87%, and freedom from migration of > or =10 mm was 83%. An endoleak was present in 11 (9%) of 122 patients at baseline, 7 (7%) of 96 at 12 months, 6 (9%) of 68 at 24 months, and 1 (3%) of 33 at 36 months. Neck dilation was not associated with graft migration or endoleak., Conclusions: Three years after endovascular repair of DTA aneurysms, there is progressive enlargement of the proximal and distal aortic necks. Although uncommon for patients to develop significant neck dilation, when it does occur, it is not associated with graft migration or endoleak. Continued surveillance of aortic neck morphology after descending thoracic aneurysm endografting is recommended.

Mesenteric ischemia/reperfusion (IR) damages the gastrointestinal epithelia and impairs gut function. Ischemic preconditioning (IPC) has been shown to protect organs against IR injury. We hypothesized that IPC protects the gut from IR injury. Rats were randomized to a sham group, a sham early IPC + IR group (sham IPC + SMA occlusion for 30 min and 6 h of reperfusion), an early IPC + IR group (IPC, three cycles of SMA occlusion for 4 min and reperfusion for 10 min) followed immediately by SMA occlusion for 30 min and 6 h of reperfusion), a sham 24-h group, a sham late IPC + IR group (sham IPC followed by additional reperfusion for 24 h + SMA occlusion for 30 min and 6 h of reperfusion), and a late IPC + IR group (IPC protocol followed by additional reperfusion for 24 h, and then SMA occlusion for 30 min followed by 6 h of reperfusion). At 6 h, transit was determined and expressed as the mean geometric center. Ileum was harvested for assessment of mucosal injury and myeloperoxidase (MPO) activity. Tissue water was determined using the wet-to-dry weight ratio to assess gut edema. Early IPC + IR significantly improved transit (3.9 +/- 0.2), decreased MPO levels (3 +/- 2), and lessened mucosal injury (1.2 +/- 0.3) compared with animals subjected to sham early IPC + IR (transit, 2.9 +/- 0.2; MPO levels, 9 +/- 1; mucosal injury, 3.0 +/- 0.6). Late IPC + IR also improved transit (6.0 +/- 0.4) and decreased MPO levels (1 +/- 1) compared with sham late IPC + IR (transit, 4.4 +/- 0.2; MPO levels, 8 +/- 1), however, there was no difference in the mucosal protection between late IPC + IR (1 +/- 0.3) and sham late IPC + IR (1 +/- 1). Our results suggest that early and late IPC improves intestinal dysfunction, decreases inflammation, and provides mucosal protection in the intestine after IR. Our results show that IR-induced gut dysfunction can be improved by IPC. Both phases of IPC can potentially be useful in the clinical setting of surgical patient care.

Introduction: Despite advances in organ protection during thoracoabdominal aortic aneurysm (TAAA) repair, acute renal failure (ARF) remains a significant clinical problem, associated with increased morbidity and mortality. We studied outcome of ARF after TAAA repair in patients who underwent either warm or cold visceral perfusion., Method: Between 1991 and 2001 657 TAAA repairs were performed, of which 359 (55%) had either warm or cold visceral perfusion. Twelve patients with renal failure who had undergone preoperative dialysis were excluded from the study. Of the remaining 347 patients, ARF developed in 81 (23%) after TAAA repair. Forty-four (54%) of the 81 patients with ARF received cold visceral perfusion, and 37 (46%) patients received warm visceral perfusion. ARF was defined as either an increase of 1 mg/dL in serum creatinine (SCr) concentration per day for 2 consecutive days or dialysis requirement. Patient records were reviewed through hospital discharge., Results: Twenty six (32%) of the 81 patients in whom ARF developed died, 17 of 37 (46%) patients in the warm perfusion group versus 9 of 44 (21%) patients in the cold perfusion group (P <.02). Median onset of ARF was on postoperative day 1 in both groups. Twenty-six of 81 (32%) patients recovered renal function, 10 of 37 (27%) patients in the warm perfusion group versus 16 of 44 (36%) patients in the cold perfusion group. Preoperative SCr concentration was predictive of recovery of renal function (odds ratio, 4.5 per mg/dL increase; P <.03) in patients who received either warm or cold visceral perfusion., Conclusions: ARF after TAAA repair remains a significant clinical problem. Recovery of renal function occurred in approximately one third of patients. Preoperative SCr concentration was the only significant determinant of recovered renal function. While cold visceral perfusion did not alter renal recovery, it significantly reduced hospital mortality.

Objective: To report the long-term results of our experience using cerebrospinal fluid drainage and distal aortic perfusion in descending thoracic and thoracoabdominal aortic repair., Summary Background Data: Repair of thoracoabdominal and thoracic aortic aneurysm by the traditional clamp-and-go technique results in a massive ischemic insult to several major organ systems. Ten years ago, we began to use distal aortic perfusion and cerebrospinal fluid drainage (adjunct) to reduce end-organ ischemia., Methods: Between January 1991 and February 2003, we performed 1004 thoracoabdominal or descending thoracic repairs. Adjunct was used in 741 (74%) of 1004. Multivariable data were analyzed by Cox regression. Number needed to treat was calculated as the reciprocal of the risk difference., Results: Immediate neurologic deficit was 18 (2.4%) of 741 with adjunct and 18 (6.8%) of 263 without (P < 0.0009). In high-risk extent II aneurysms, the numbers were 11 (6.6%) of 167 with adjunct, and 11 (29%) of 38 without. Long-term survival was improved with adjunct (P < 0.002). The long-term survival results persisted after adjustment for age, extent II aneurysm, and preoperative renal function., Conclusion: Use of adjunct over a long period of time has produced favorable results; approximately 1 neurologic deficit saved for every 20 uses of adjunct overall. In extent II aneurysms, where the effect is greatest, this increases to 1 saved per 5 uses. Adjunct is also associated with long-term survival, which is consistent with mitigation of ischemic end-organ injury. These long-term results indicate that cerebrospinal fluid drainage and distal aortic perfusion are safe and effective adjunct for reducing morbidity and mortality following thoracic and thoracoabdominal aortic repair.

Background & Aims: Gastrointestinal function may be impaired after severe injury, hampering tolerance to enteral nutrition. The purpose of this study was to determine how different sodium-coupled solutes modulate gut function after ischemia/reperfusion (I/R) in a rodent model., Methods: At laparotomy, rats had jejunal sacs filled with (glucose + alanine), glucose, glutamine, alanine, or mannitol (osmotic control), followed by superior mesenteric artery clamping for 60 minutes and 30 minutes of reperfusion. After reperfusion, sacs were harvested for morphologic examination, adenosine triphosphate (ATP) assay, or mounted in an Ussing chamber., Results: Small intestinal epithelial absorptive capacity, as assessed by changes in short-circuit current in response to glucose, after gut I/R, was decreased by alanine or (glucose + alanine) but not glucose or glutamine alone and correlated with changes in tissue ATP. Gut I/R caused a significant morphologic injury that was worsened by alanine or (glucose + alanine) but lessened by glucose or glutamine alone., Conclusions: During gut I/R, alanine can enhance gut injury, deplete energy (ATP), and impair gut absorption, whereas glucose or glutamine is protective against injury and can maintain absorptive capacity and ATP. These results suggest that solutes (such as alanine), which further stress an already metabolically stressed bowel, should be cautiously administered to critically ill patients whereas those solutes that contribute to energy production (such as glucose and glutamine) may be safely continued.

Mesenteric ischemia-reperfusion (I/R) injury to the intestine is a common and often devastating clinical occurrence for which there are few therapeutic options. alpha-Melanocyte-stimulating hormone (alpha-MSH) is a tridecapeptide released by the pituitary gland and immunocompetent cells that exerts anti-inflammatory actions and abrogates postischemic injury to the kidneys and brainstem of rodents. To test the hypothesis that alpha-MSH would afford similar protection in the postischemic small intestine, we analyzed the effects of this peptide on intestinal transit, histology, myeloperoxidase activity, and nuclear factor-kappaB (NF-kappaB) activation after 45 min of superior mesenteric artery occlusion and

Objective: chronic aortic dissection has long been considered a risk factor for neurologic deficit following thoracoabdominal aortic aneurysm (TAA) surgery. We reviewed our experience with regard to aneurysm extent and the use of adjunct, (distal aortic perfusion/cerebrospinal fluid drainage), and examined the impact of these factors on neurologic deficit among chronic dissection and non-dissection cases., Methods: between February 1991 and March 2001, we repaired 800 aneurysms of the descending thoracic and thoracoabdominal aorta. Seven hundred and twenty-nine cases were elective; 196 chronic dissection, 533 non-dissection. 182/729 (24.9%) were TAA extent II. Among these, 61/182 (33%) involved chronic dissection. Adjunct was used in 507/729 (69.6%). We conducted detailed multivariate analyses to isolate the impact of chronic aortic dissection on neurologic morbidity, with other important risk factors taken into account., Results: overall, 32/729 (4.4%) patients had neurologic deficit upon awakening; 7/196 (3.6%) in chronic dissections, and 25/533 (4.7%) in non-dissections. Adjunct had a major effect, reducing neurologic deficit in TAA extent II from 10/36 (27.8%) to 10/146 (6.9%) (p=0.001). However, in univariate and multivariate analysis, chronic dissection did not increase the risk of neurologic deficit, regardless of extent or mode of treatment., Conclusion: in contrast to previous reports, we determined that chronic aortic dissection is not a risk factor in TAA patients., (Copyright 2002 Harcourt Publishers Limited.)

Despite intensive investigation, the pathogenesis of post-injury multiple organ failure (MOF) remains elusive. Laboratory and clinical research strongly suggests that the gastrointestinal tract (i.e., the gut) plays a pivotal pathogenic role. Since its inception in 1988, the Trauma Research Center (TRC) at the University of Texas-Houston Medical School (UTHMS) has focused its efforts on elucidating the role of the gut in post-injury MOF. On the basis of our observations and those of others, we believe that 1) shock with resulting gut hypoperfusion is an important inciting event, 2) the reperfused gut is a source of proinflammatory mediators that can amplify the early systemic inflammatory response syndrome (SIRS) and thus contribute to early MOF, 3) early gut hypoperfusion causes an ileus in both the stomach and small bowel that sets the stage for progressive gut dysfunction so that the proximal gut becomes a reservoir for pathogens and toxins that contribute to late sepsis-associated MOF, and 4) late infections cause further worsening of this gut dysfunction. Thus, the gut can be both an instigator and a victim of MOF. The purpose of this article is to provide the rationale behind these beliefs and to provide a brief overview of the ongoing research projects in the TRC at UTHMS.