Advances and Challenges in Interventional Immuno-Oncology Locoregional Therapies.

Interventional immuno-oncology is making strides in locoregional therapies to address complex tumor microenvironments. Long-standing interventional radiology cancer therapies, such as tumor ablation and embolization, are being recharacterized in the context of immunotherapy. Intratumoral injections, such as those of genetically engineered or unaltered viruses, and the delivery of immune cells, antibodies, proteins, or cytokines into targeted tumors, along with advancements in delivery techniques, have produced promising results in preliminary studies, indicating their antitumor effectiveness. Emerging strategies using DNA scaffolding, polysaccharides, glycan, chitosan, and natural products are also showing promise in targeted cancer therapy. The future of interventional immuno-oncology lies in personalized immunotherapies that capitalize on individual immune profiles and tumor characteristics, along with the exploration of combination therapies. This study will review various interventional immuno-oncology strategies and emerging technologies to enhance delivery of therapeutics and response to immunotherapy.

Prospective Evaluation of Immune Activation Associated with Response to Radioembolization Assessed with PET/CT in Women with Breast Cancer Liver Metastasis.

Background The impact of transarterial radioembolization (TARE) of breast cancer liver metastasis (BCLM) on antitumor immunity is unknown, which hinders the optimal selection of candidates for TARE. Purpose To determine whether response to TARE at PET/CT in participants with BCLM is associated with specific immune markers (cytokines and immune cell populations). Materials and Methods This prospective pilot study enrolled 23 women with BCLM who planned to undergo TARE (June 2018 to February 2020). Peripheral blood and liver tumor biopsies were collected at baseline and 1-2 months after TARE. Monocyte, myeloid-derived suppressor cell (MDSC), interleukin (IL), and tumor-infiltrating lymphocyte (TIL) levels were assessed with use of gene expression studies and flow cytometry, and immune checkpoint and cell surface marker levels with immunohistochemistry. Modified PET Response Criteria in Solid Tumors was used to determine complete response (CR) in treated tissue. After log-transformation, immune marker levels before and after TARE were compared using paired t tests. Association with CR was assessed with Wilcoxon rank-sum or unpaired t tests. Results Twenty women were included. After TARE, peripheral IL-6 (geometric mean, 1.0 vs 1.6 pg/mL; P = .02), IL-10 (0.2 vs 0.4 pg/mL; P = .001), and IL-15 (1.9 vs 2.4 pg/mL; P = .01) increased. In biopsy tissue, lymphocyte activation gene 3-positive CD4+ TILs (15% vs 31%; P < .001) increased. Eight of 20 participants (40% [exact 95% CI: 19, 64]) achieved CR. Participants with CR had lower baseline peripheral monocytes (10% vs 29%; P < .001) and MDSCs (1% vs 5%; P < .001) and higher programmed cell death protein (PD) 1-positive CD4+ TILs (59% vs 26%; P = .006) at flow cytometry and higher PD-1+ staining in tumor (2% vs 1%; P = .046). Conclusion Complete response to transarterial radioembolization was associated with lower baseline cytokine, monocyte, and myeloid-derived suppressor cell levels and higher programmed cell death protein 1-positive tumor-infiltrating lymphocyte levels. © RSNA, 2022 Online supplemental material is available for this article.

Society of Interventional Radiology Foundation Funding to National Institutes of Health Funding: Report from the Society of Interventional Radiology Foundation/National Institutes of Health Task Force.

The Society of Interventional Radiology Foundation (SIRF) aims to support interventional radiology (IR) investigators by awarding numerous grants to promote the advancement of scientific knowledge in IR. Over the last 19 years, SIRF has awarded 227 research grants, amounting to more than $4.7 million. To increase the engagement of interventional radiologists and IR scientists with the National Institutes of Health (NIH), SIRF created a SIRF/NIH taskforce in 2020. Over the past couple of years, the task force has been working to assess the return on investment of SIRF grants in terms of NIH funding because this metric is an effective measure of assessing the early success of foundation funding. The objectives of this report are to assess SIRF funding from 2002 to 2020 and investigate the conversion of this funding into NIH grants by the same investigators. During the study period, more than $37.6 million in NIH funds were awarded to SIRF awardees, which shows a return of 8 NIH dollars for every 1 SIRF dollar invested.

Percutaneous Transesophageal Gastrostomy: Procedural Technique and Outcomes.

PURPOSE: To demonstrate the safety and effectiveness of percutaneous transesophageal gastrostomy (PTEG) as a palliative option in patients with malignant bowel obstructions (MBOs), and provide a comprehensive review of PTEG indications, placement technique, and short- and long-term outcomes. MATERIALS AND METHODS: Thirty-eight consecutive patients who underwent a PTEG procedure attempt from 2014 to 2022 were included in this analysis. Clinical indications, method of placement, technical and clinical success, adverse events, including procedure-related mortality, and effectiveness were assessed. Technical success was defined as placement of a PTEG. Clinical success was defined as improvement in clinical symptoms following PTEG placement. RESULTS: Of the 38 patients who underwent PTEG, 19 (50%) were men and 19 (50%) were women (median age, 58 years; range, 21-75 years). Three (8%) PTEG placements were performed with the patients under moderate sedation, whereas the remainder (92%) were performed with the patients under general anesthesia. Technical success was achieved in 35 of the 38 (92%) patients. The mean catheter duration was 61 days (median, 29 days; range, 1-562 days), with 5 of the 35 patients requiring tube exchanges after initial placement. Moreover, 7 of the 35 patients with successful PTEG placement experienced an adverse event, including 1 case of non-procedure-related mortality. All patients with successful PTEG placement experienced improvement in clinical symptoms. CONCLUSIONS: PTEG is an effective and safe option for patients with contraindications to traditional percutaneous gastrostomy tube placement in the setting of MBO. PTEG is an effective means of providing palliation and improving the quality of life.

Interventional Management of Acquired Lymphatic Disorders.

The lymphatic system is a complex network of tissues, vessels, and channels found throughout the body that assists in fluid balance and immunologic function. When the lymphatic system is disrupted related to idiopathic, iatrogenic, or traumatic disorders, lymphatic leaks can result in substantial morbidity and/or mortality. The diagnosis and management of these leaks is challenging. Modern advances in lymphatic imaging and interventional techniques have made radiology critical in the multidisciplinary management of these disorders. The authors provide a review of conventional and clinically relevant variant lymphatic anatomy and recent advances in diagnostic techniques such as MR lymphangiography. A detailed summary of technical factors related to percutaneous lymphangiography and lymphatic intervention is presented, including transpedal and transnodal lymphangiography. Traditional transabdominal access and retrograde access to the central lymph nodes and thoracic duct embolization techniques are outlined. Newer techniques including transhepatic lymphangiography and thoracic duct stent placement are also detailed. For both diagnostic and interventional radiologists, an understanding of lymphatic anatomy and modern diagnostic and interventional techniques is vital to the appropriate treatment of patients with acquired lymphatic disorders. ©RSNA, 2022.

Transsplenic Portal System Catheterization: Review of Current Indications and Techniques.

Multiple diseases of the portal system require effective portal vein access for endovascular management. While percutaneous transhepatic and transjugular approaches remain the standard methods of portal vein access, transsplenic access (TSA) has gained recognition as an effective and safe technique to access the portal system in patients with contraindications to traditional approaches. Recently, the utility of percutaneous TSA has grown, with described treatments including recanalization of chronic portal vein occlusion, placement of stents for portal vein stenosis, portal vein embolization of the liver, embolization of gastric varices, placement of complicated transjugular intrahepatic portosystemic shunts, and interventions after liver transplant. The authors provide a review of percutaneous TSA, including indications, a summary of related portal vein diseases, and the different techniques used for access and closure. In addition, an imaging-based review of technical considerations of TSA interventions is presented, with a review of potential procedural complications. With technical success rates that mirror or rival the standard methods and reported low rates of major complications, TSA can be a safe and effective option in clinical scenarios where traditional approaches are not feasible. ©RSNA, 2022.

Venous Anatomy and Collateral Pathways of the Pelvis: An Angiographic Review.

The pelvic venous system is complex, with the potential for numerous pathways of collateralization. Owing to stenosis or occlusion, both thrombotic and nonthrombotic entities in the pelvis may necessitate alternate routes of venous return. Although the pelvic venous anatomy and collateral pathways may demonstrate structural variability, a number of predictable paths often can be demonstrated on the basis of the given disease and the level of obstruction. Several general categories of collateral pathways have been described. These pathway categories include the deep pathway, which is composed of the lumbar and sacral veins and vertebral venous plexuses; the superficial pathway, which is composed of the circumflex and epigastric vessels; various iliofemoral collateral pathways; the intermediate pathway, which is composed of the gonadal veins and the ovarian and uterine plexuses; and portosystemic pathways. The pelvic venous anatomy has been described in detail in cadaveric and anatomic studies, with the aforementioned collateral pathways depicted on CT and MR images in several imaging studies. A comprehensive review of the native pelvic venous anatomy and collateralized pelvic venous anatomy based on angiographic features has yet to be provided. Knowledge of the diseases involving a number of specific pelvic veins is of clinical importance to interventional and diagnostic radiologists and surgeons. The ability to accurately identify common collateral patterns by using multiple imaging modalities, with accurate anatomic descriptions, may assist in delineating underlying obstructive hemodynamics and diagnosing specific occlusive disease entities. ©RSNA, 2022.

Interventional Radiology Management of Adult Liver Transplant Complications.

Liver transplant remains the definitive therapy for patients with end-stage liver disease. Outcomes have continued to improve, in part owing to interventions used to treat posttransplant complications involving the hepatic arteries, portal vein, hepatic veins or inferior vena cava (IVC), and biliary system. Significant hepatic artery stenosis can be treated with angioplasty or stent placement to prevent thrombosis and biliary ischemic complications. Hepatic arterioportal fistula and hepatic artery pseudoaneurysm are rare complications that can often be treated with endovascular means. Treatment of hepatic artery thrombosis can have mixed results. Portal vein stenosis can be treated with venoplasty or more commonly stent placement. The rarer portal vein thrombosis can also be treated with endovascular techniques. Hepatic venous outflow stenosis of the hepatic veins or IVC is amenable to venoplasty or stent placement. Complications of the bile ducts are the most encountered complication after liver transplant. When not amenable to endoscopic intervention, biliary stricture, bile leak, and ischemic cholangiopathy can be treated with percutaneous transhepatic cholangiography with biliary drainage and other interventions. New techniques have further improved care for these patients. Transsplenic portal vein recanalization has improved transplant candidacy for patients with chronic portal vein thrombosis. Spontaneous splenorenal shunt and splenic artery steal syndrome (nonocclusive hepatic artery hypoperfusion syndrome) remain complicated topics, and the role of endovascular embolization is developing. When patients have recurrence of cirrhosis after transplant, most commonly due to viral hepatitis, transjugular intrahepatic portosystemic shunt (TIPS) may be required to treat symptoms of portal hypertension. Online supplemental material is available for this article. ©RSNA, 2022.

Interventional Radiology Obesity Therapeutics: Proceedings from the Society of Interventional Radiology Foundation Research Consensus Panel.

The Society of Interventional Radiology Foundation commissioned a Research Consensus Panel to establish a research agenda on "Obesity Therapeutics" in interventional radiology (IR). The meeting convened a multidisciplinary group of physicians and scientists with expertise in obesity therapeutics. The meeting was intended to review current evidence on obesity therapies, familiarize attendees with the regulatory evaluation process, and identify research deficiencies in IR bariatric interventions, with the goal of prioritizing future high-quality research that would move the field forward. The panelists agreed that a weight loss of >8%-10% from baseline at 6-12 months is a desirable therapeutic endpoint for future IR weight loss therapies. The final consensus on the highest priority research was to design a blinded randomized controlled trial of IR weight loss interventions versus sham control arms, with patients receiving behavioral therapy.

Dose reduction using digital fluoroscopy versus digital subtraction angiography in endovascular aneurysm repair: A prospective randomized trial.

OBJECTIVE: Endovascular aneurysm repair (EVAR) can result in high radiation dose to patients and operators. This prospective randomized study aimed to assess whether patient radiation dose sustained during EVAR could be decreased by predominantly using digital fluoroscopy (DF) vs the standard technique using digital subtraction angiography (DSA). METHODS: Between February 2011 and June 2017, patients with EVAR of infrarenal abdominal aortic aneurysms were prospectively enrolled and randomly assigned to a standard treatment DSA cohort or a DF cohort in which two or fewer DSA acquisitions were allowed for confirmatory imaging. Primary end points included dose-area product (DAP) and cumulative air kerma. Secondary end points included technical success and conversion to DSA standard treatment (if DF was inadequate for visualization). RESULTS: For all 43 patients enrolled (26 in the DF cohort, 17 in the DSA cohort), technical success was 100%. Of the 26 DF patients, 5 (19%) required conversion to the DSA cohort. In an intention-to-treat analysis, mean DAP was significantly lower in the DF cohort than in the DSA cohort (132 vs 174 Gy·cm2; P = .04). When patients were separated by number of DSA acquisitions (two or fewer vs three or more), mean DAP decreased 41% (109 vs 185 Gy·cm2; P = .005) and cumulative air kerma decreased 40% (578 vs 964 mGy; P = .004). CONCLUSIONS: In most patients (81%), DF or limited DSA was adequate for visualization during EVAR. In both intention-to-treat DF and limited-DSA cohorts, mean DAP was significantly decreased. If image quality allows, a DF-only or limited-DSA approach to EVAR decreases radiation dose.

Sample content of kinesthetic educational training: Reducing scattered X-ray exposures to interventional physician operators of fluoroscopy.

Content used by Medical Physicists for fluoroscopy safety training to staff is deliverable via several formats, that is, online content or a live audience slide presentations. Here, we share one example of a kinesthetic (live, hands-on simulation) educational program in use at our facility for some time (~10 years). In this example, the format and content specifically target methods of reducing physician operator exposures from scattered x rays. A kinesthetic format identifies and promotes the adoption of exposure-reducing behaviors. Key kinesthetic elements of this type of training include: physician hands-on measurements of radiation levels at locations specific to their standing positions (e.g., primary arterial access points) in the room using handheld exposure rate meters, measurement of exposure rate reduction to physicians provided by using personal protective equipment, that is, wearable aprons, hanging lead drapes, and pull-down shields. Physician choice of procedure-specific tableside selectable controls affecting exposure rate from optional fluoroscopy, Cine or digital subtraction angiography (DSA), along with comparative measured contribution to physician exposure is demonstrated. The inverse square exposure rate reduction to physicians when stepping back from the table during DSA is a key observation. Kinesthetic simulations in the rooms used by physicians have been found to provide the highest level of understanding giving rise to adoption of practices that are impactful for physicians. Specific training scripts are in place for physician sub-specialization in interventional radiology, cardiology, neurosurgery, vascular surgery, and gastroenterology. This training is used for new physician staff while classroom presentations (whose content mimics in room training) are used with staff who have had previously had in room training.

Computed tomography angiography evaluation of acute limb ischemia.

Acute limb ischemia (ALI), a subclass of critical limb ischemia, is a medical emergency. The cause of ALI is usually thrombotic or embolic in nature, and the specific etiology often dictates the appropriate therapy. While the diagnosis is a clinical with common presenting symptoms, advances in ultrasound, computed tomography, and magnetic resonance technology have impacted the diagnosis and subsequent therapy. In ALI, the time to revascularization is critical and computed tomography angiography (CTA) provides a highly sensitive and specific technique for rapidly identifying occlusions and precisely defining vascular anatomy prior to interventions. In patients with significant renal disease, magnetic resonance angiography with or without contrast provides effective alternatives at the expense of imaging time. Treatment can include a variety of endovascular or surgical interventions, including thromboembolectomy, angioplasty, or bypass. Proper evaluation of the etiology of the ischemia, affected vasculature, and medical history is critical to select appropriate treatment and improve patient outcomes. Here, we examine the presentation, evaluation, and treatment of ALI and the role of CTA in diagnosis and therapy.

Segmental Arterial Mediolysis: Abdominal Imaging of and Disease Course in 111 Patients.

OBJECTIVE: The purpose of this study is to identify the imaging characteristics of segmental arterial mediolysis (SAM) at presentation and establish the longitudinal course of disease. MATERIALS AND METHODS: We retrospectively identified patients with SAM at a single institution from 2000 through 2015. Diagnosis was based on published guidelines with multidisciplinary consensus. Imaging studies obtained at initial evaluation were reviewed to evaluate imaging findings and vascular territory distribution. All subsequent follow-up imaging studies were reviewed to assess for progression, stability, or regression. RESULTS: We identified 111 patients (79 men and 32 women; median age, 51 years) who met the diagnostic criteria for SAM. Abdominal pain was the most common presentation (74%), followed by flank pain (21%). SAM most commonly affected the renal arteries (47%), superior mesenteric artery (46%), celiac trunk (46%), hepatic artery (23%), iliac arteries (18%), and splenic artery (14%). The most common imaging findings were dissection (86%), aneurysm (57%), beading or webs (28%), occlusion (19%), and a rind or wall thickening (15%). The 247 available follow-up imaging studies for 97 patients (median follow-up, 12 months) showed progression in 19 patients (20%), with either stability or regression observed in the remaining patients. CONCLUSION: SAM most commonly affects the renal arteries, superior mesenteric artery, and celiac artery. Dissections and aneurysms are the most common imaging findings. Follow-up imaging studies show stability or regression in most patients.

Novel targeted therapy strategies for biliary tract cancers and hepatocellular carcinoma.

Worldwide hepatobiliary cancers are the second leading cause of cancer related death. Despite their relevance, hepatobiliary cancers have a paucity of approved systemic therapy options. However, there are a number of emerging therapeutic biomarkers and therapeutic concepts that show promise. In hepatocellular carcinoma, nivolumab appears particularly promising and recently received US FDA approval. In intrahepatic cholangiocarcinoma, therapies targeting FGFR2 and IDH1 and immune checkpoint inhibitors are the furthest along and generating the most excitement. There are additional biomarkers that merit further exploration in hepatobiliary cancers including FGF19, ERRFI1, TERT, BAP1, BRAF, CDKN2A, tumor mutational burden and ERBB2 (HER2/neu). Development of new and innovative therapies would help address the unmet need for effective systemic therapies in advanced and metastatic hepatobiliary cancers.

Needlestick Injuries in Interventional Radiology Are Common and Underreported.

Purpose To determine the prevalence of and risk factors for needlesticks in interventional radiology physicians, as well as the attitudes, behaviors, and conditions that promote or interfere with reporting of these injuries. Materials and Methods A total of 3889 interventional radiologists from academic and private practice in the United States were surveyed by emailing all interventional radiologist members of the Society of Interventional Radiology, including attending-level physicians and trainees (April-August 2016). The institutional review board waived the need for consent. Questions inquired about the nature, frequency, and type of needlestick and sharps injuries and whether and to whom these incidents were reported. Stepwise regression was used to determine variables predicting whether injuries were reported. Results In total, 908 (23%) interventional radiologists completed at least a portion of the survey. Eight hundred fourteen (91%) of 895 respondents reported a prior needlestick injury, 583 (35%) of 895 reported at least one injury while treating an HIV-positive patient, and 626 (71%) of 884 reported prior training regarding needlestick injury. There was, on average, one needlestick for every 5 years of practice. Most needlestick or sharps injuries were self inflicted (711 [87%] of 817) and involved a hollow-bore device (464 [56%] of 824). Only 566 (66%) of 850 injuries were reported. The most common reasons for not reporting included perceived lack of utility of reporting (79 [28%] of 282), perceived low risk for injury (56 [20%] of 282), noncontaminated needle (53 [19%] of 282), too-lengthy reporting process (37 [13%] of 282), and associated stigma (23 [8%] of 282). Only 156 (25%) of 624 respondents informed their significant other. Stepwise regression assessing variables affecting the likelihood of reporting showed that male sex (P = .009), low-risk patient (P < .0001), self injury (P = .010), trainee status (P < .0001), and the total number of prior injuries (P = .019) were independent predictors of not reporting. Conclusion Needlestick injuries are ubiquitous among interventional radiologists and are often not reported. © RSNA, 2017 Online supplemental material is available for this article.

Spinal Cord Inflammation: Molecular Imaging after Thoracic Aortic Ischemia Reperfusion Injury.

Purpose To evaluate whether noninvasive molecular imaging technologies targeting myeloperoxidase (MPO) can reveal early inflammation associated with spinal cord injury after thoracic aortic ischemia-reperfusion (TAR) in mice. Materials and Methods The study was approved by the institutional animal care and use committee. C57BL6 mice that were 8-10 weeks old underwent TAR (n = 55) or sham (n = 26) surgery. Magnetic resonance (MR) imaging (n = 6) or single photon emission computed tomography (SPECT)/computed tomography (CT) (n = 15) studies targeting MPO activity were performed after intravenous injection of MPO sensors (bis-5-hydroxytryptamide-tetraazacyclododecane [HT]-diethyneletriaminepentaacetic acid [DTPA]-gadolinium or indium 111-bis-5-HT-DTPA, respectively). Immunohistochemistry and flow cytometry were used to identify myeloid cells and neuronal loss. Proinflammatory cytokines, keratinocyte chemoattractant (KC), and interleukin 6 (IL-6) were measured with enzyme-linked immunosorbent assay. Statistical analyses were performed by using nonparametric tests and the Pearson correlation coefficient. P < .05 was considered to indicate a significant difference. Results Myeloid cells infiltrated into the injured cord at 6 and 24 hours after TAR. MR imaging confirmed the presence of ischemic lesions associated with mild MPO-mediated enhancement in the thoracolumbar spine at 24 hours compared with the sham procedure. SPECT/CT imaging of MPO activity showed marked MPO-sensor retention at 6 hours (P = .003) that continued to increase at 24 hours after TAR (P = .0001). The number of motor neurons decreased substantially at 24 hours after TAR (P < .01), which correlated inversely with in vivo inflammatory changes detected at molecular imaging (r = 0.64, P = .0099). MPO was primarily secreted by neutrophils, followed by lymphocyte antigen 6 complexhigh monocytes and/or macrophages. There were corresponding increased levels of proinflammatory cytokines KC (P = .0001) and IL-6 (P = .0001) that mirrored changes in MPO activity. Conclusion MPO is a suitable imaging biomarker for identifying and tracking inflammatory damage in the spinal cord after TAR in a mouse model. © RSNA, 2016 Online supplemental material is available for this article.

Association Between Allergies and Psychiatric Disorders in Patients Undergoing Invasive Procedures.

BACKGROUND: Associations between allergies and psychiatric disorders have been reported in the context of depression and suicide; psychiatric disorders may affect pain perception. OBJECTIVE: To investigate the relationship of allergies with psychiatric disorders and pain perception in the context of invasive procedures, specifically during tunneled hemodialysis catheter placement. METHODS: We identified 89 patients (51 men, 38 women), mean age 66 years (range: 23-96), who underwent tunneled hemodialysis catheter placement (1/2014-2/2015), recording numeric rating scale pain scores, medications, psychiatric history, allergies, and smoking status. RESULTS: Of 89 patients, 47 patients had no allergies, and 42 had ≥1 allergy. Patients with allergies were more likely to have a pre-existing psychiatric disorder compared to those without allergies, odds ratio 2.6 (95% CI: 1.0-6.8). Having allergies did not affect procedural sedation or postprocedural pain scores. Multiple logistic regression with age, sex, smoking, presence of allergies, psychiatric history, inpatient/outpatient status, procedure time, and procedural sedation administration as inputs and postprocedural pain as the outcome showed that the only independent predictor was receiving procedural sedation (P = 0.005). CONCLUSIONS: Findings corroborate anecdotal reports of allergies as a marker for psychiatric history. However, having allergies was not associated with increased pain or need for more sedation. Further studies could prospectively assess whether allergies and psychiatric disorders affect patient/doctor perceptions beyond pain during invasive procedures.

Kidney and Liver Injuries After Major Burns in Rats Are Prevented by Resolvin D2.

OBJECTIVES: Innate immune dysfunction after major burn injuries increases the susceptibility to organ failure. Lipid mediators of inflammation resolution, e.g., resolvin D2, have been shown recently to restore neutrophil functionality and reduce mortality rate in a rat model of major burn injury. However, the physiological mechanisms responsible for the benefic activity of resolvin D2 are not well understood. DESIGN: Prospective randomized animal investigation. SETTING: Academic research setting. SUBJECTS: Wistar male rats. INTERVENTIONS: Animals were subjected to a full-thickness burn of 30% total body surface area. Two hours after burn, 25 ng/kg resolvin D2 was administered IV and repeated every day, for 8 days. At day 10 post burn, 2 mg/kg of lipopolysaccharide was administered IV, and the presence of renal and hepatic injuries was evaluated at day 11 post burn by histology, immunohistochemistry, and relevant blood chemistry. MEASUREMENTS AND MAIN RESULTS: In untreated animals, we found significant tissue damage in the kidneys and liver, consistent with acute tubular necrosis and multifocal necrosis, and changes in blood chemistry, reflecting the deterioration of renal and hepatic functions. We detected less tissue damage and significantly lower values of blood urea nitrogen (26.4 ± 2.1 vs 36.0 ± 9.3 mg/dL; p ≤ 0.001), alanine aminotransferase (266.5 ± 295.2 vs 861.8 ± 813.7 U/L; p ≤ 0.01), and total bilirubin (0.13 ± 0.05 vs 0.30 ± 0.14 mg/dL; p ≤ 0.01) in resolvin D2-treated rats than in untreated animals. The mean blood pressure of all animals was above 65 mm Hg, indicating adequate tissue perfusion throughout the experiments. We measured significantly larger amounts of chromatin in the circulation of untreated than of resolvin D2-treated rats (575.1 ± 331.0 vs 264.1 ± 122.4 ng/mL; p ≤ 0.05) and identified neutrophil extracellular traps in kidney and liver tissues from untreated rats, consistent with the tissue damage. CONCLUSIONS: Pathologic changes in kidney and liver tissues in a rat model of major burn and endotoxin insults are ameliorated by resolvin D2.

Ethyl pyruvate modulates delayed paralysis following thoracic aortic ischemia reperfusion in mice.

OBJECTIVE: Delayed paralysis is an unpredictable problem for patients undergoing complex repair of the thoracic/thoracoabdominal aorta. These experiments were designed to determine whether ethyl pyruvate (EP), a potent anti-inflammatory and antioxidant agent, might ameliorate delayed paralysis following thoracic aortic ischemia reperfusion (TAR). METHODS: C57BL6 mice were subjected to 5 minutes of thoracic aortic ischemia followed by reperfusion for up to 48 hours. Mice received either 300 mg/kg EP or lactated ringers (LR) at 30 minutes before ischemia and 3 hours after reperfusion. Neurologic function was assessed using an established rodent scale. Spinal cord tissue was analyzed for markers of inflammation (keratinocyte chemoattractant [KC], interleukin-6 [IL-6]), microglial activation (ionized calcium-binding adapter molecule-1 [Iba-1]), and apoptosis (Bcl-2, Bax, and terminal deoxynucleotidyl transferase dUTP nick end labeling [TUNEL] staining) at 24 and 48 hours after TAR. Nissl body stained motor neurons were counted in the anterior horns sections from L1-L5 segments. RESULTS: Ninety-three percent of the LR mice developed dense delayed paralysis between 40 and 48 hours after TAR, whereas only 39% of EP mice developed delayed paralysis (P < .01). Bcl-2 expression was higher (P < .05) and Iba-1 expression was lower (P < .05) in the EP group only at 24 hours reperfusion. At 48 hours, the number of motor neurons was higher (P < .01) and the number and TUNEL-positive cells was lower (P < .001) in the EP-treated mice. EP decreased the expression of KC (P < .01) and IL-6 (P < .001) at 48 hours after TAR. CONCLUSIONS: The protection provided by EP against delayed paralysis correlated with preservation of motor neurons, higher expression of antiapoptotic molecules, decreased microglial cell activation, and decreased spinal cord inflammation. EP may be a treatment for humans at risk for delayed paralysis.