Loyola University Medical Center Research Articles

Impact of Emergency Medical Services Activation of the Cardiac Catheterization Laboratory and a 24-Hour/Day In-Hospital Interventional Cardiology Team on Treatment Times (Door to Balloon and Medical Contact to Balloon) for ST-Elevation Myocardial Infarction

The incremental benefit of emergency medical services (EMS) activation of the cardiac catheterization laboratory (CCL) for ST-elevation myocardial infarction (STEMI) in the setting of an established in-house interventional team (IHIT) is uncertain. We evaluated the impact of EMS activation on door-to-balloon (D2B) time and first medical contact-to-balloon (FMC2B) time for STEMI when coupled with a 24-hour/day IHIT. All patients presenting with STEMI to Loyola University Medical Center had demographic, procedural, and outcome data consecutively entered in a STEMI Data Registry. From 223 consecutive patients presenting between April 2009 and December 2015, a retrospective analysis was performed on 190 patients. Patients were divided into 2 groups depending on CCL activation mode (EMS activation or emergency department activation) and STEMI treatment process times were compared. The primary end point was D2B process times. The secondary end point was FMC2B process times in a subgroup analysis of EMS-transported patients. D2B times were shorter (37 ± 14 minutes vs 57 ± 27 minutes, p < 0.001) with EMS activation. Subgroup analysis of EMS-transported patients demonstrated shorter FMC2B times with EMS activation (52 ± 17 minutes vs 67 ± 32 minutes, p = 0.002). EMS activation was the only predictor of D2B ≤60 minutes in multivariable analysis of EMS-transported patients (odds ratio 9.4; 95% confidence interval 2.1 to 43.0; p = 0.04). In conclusion, EMS activation of the CCL in STEMI was associated with significant improvements in already excellent D2B and FMC2B times even in the setting of a 24-hour/day IHIT.

Generating highly potent and efficacious antibodies to the cholecystokinin B (CCK‐B) receptor by ribosome display for the treatment of neuropathic pain

Development of effective non‐opioid therapeutics tailored to specific chronic pain syndromes is sorely needed. Our recent microchip gene expression profile identified upregulated cholecystokinin B (CCK‐B) receptor in trigeminal ganglia (TG) as one suitable target among many others. Thus, the CCK‐B receptor is an ideal candidate to impact both nociceptive and limbic components of chronic pain. More importantly, its inhibition can reverse opiate tolerance. Based on the literature and the gene expression changes over time, the CCK‐B receptor is implicated as one of the persisting functional targets suitable for development of therapeutics to inhibit chronic pain‐ and anxiety‐related behaviors. Here we describe the isolation and characterization of a panel of CCK‐B receptor specific antibodies using ribosome display technology. Furthermore, we demonstrate in vivo efficacy of our antibodies in a relevant model of chronic neuropathic pain. This is the first example, to date, of scFv antibodies that can block the CCK‐B receptor directly with high potency and specificity. This highlights the exciting potential therapeutic opportunity of an antibody for blocking this type of receptor.Support or Funding InformationThis work was supported by Startup dollars from Loyola University Medical Center (RD) and University of New Mexico (KW).This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Sarcoidosis Associated Pulmonary Hypertension: Correlation of Cascular Morphologic Changes with Hemodynamic Data in Explanted Lungs

Purpose Sarcoidosis associated pulmonary hypertension (PH) is classified as WHO Group V according to the 2018 WHO classification system. Previous case series have demonstrated efficacy of pulmonary vasodilators in treating severe PH in sarcoidosis. We present a series of patients with sarcoidosis associated PH and describe correlation between the pre-transplant hemodynamic data from a right heart catheterization (RHC) and vascular morphologic changes in the native explanted lungs. Methods Patients with sarcoidosis who underwent lung transplantation at Loyola University Medical Center were analyzed from 2014-2018. We collected demographic data, RHC data, NYHA functional class data, and echocardiogram. Pathology was reviewed to assess for presence and severity of fibrosis, presence or absence of granulomas in lung parenchyma and lymph nodes, and vascular morphologic changes using Heath Edwards PH classification. We evaluated PH changes in arterioles, muscular arteries of 1mm and 3mm caliber, and elastic arteries. These findings were correlated to RHC data. Results Seven patients who had a RHC prior to lung transplantation were identified and had a mean pulmonary artery pressure greater than 25 mmHg. All of the patients had well-formed granulomas except two cases that showed ill formed granulomas. 5 of 7 cases had lymph nodes involved and 5 of 7 had fibrosis. Medial hypertrophy of 1 and 3mm arteries was observed in all cases. 3 of 4 patients with severe PH (NYHA Class IV) and RV dysfunction on echocardiogram were on parenteral prostacyclin therapy at the time of transplant and had grade 3 changes in the 1 mm arteries and grade 2 changes in the 3 mm arteries. Only 2 of 7 cases showed arteriolar changes, which correlated with higher pressures. No plexiform lesions were seen in any of the patients. Conclusion In our series of sarcoidosis patients with PH who underwent lung transplant or transplantation, vascular morphologic changes at the level of the 1 mm and arterioles correlated with the presence of severe PH (NYHA Class IV) and RV dysfunction on echocardiogram. These patients lack the plexiform lesions typically seen in idiopathic pulmonary arterial hypertension. Our study may identify a subset of sarcoid patients who have significant vascular remodeling and possibly explains the recently observed favorable response to vasodilator therapy.

Medical Students as Certified Interpreters.

Spanish speakers make up 13.1% of the US population, and language barriers contribute to health disparities. Medical interpreters are essential for communication between patients with limited English proficiency (LEP) and their clinicians. However, there is a shortage of interpreters nationwide; free clinics, where a large majority of patients with LEP receive care, are especially affected by this shortage. Many medical schools are associated with a free clinic, and medical students who speak Spanish can help fill this gap. Loyola University Chicago Stritch School of Medicine, together with Interpreter Services at Loyola University Medical Center, created an interpreter certification program for medical students. Although there are challenges in certifying medical students as interpreters, doing so helps to build a workforce of well-trained, culturally competent physicians.

201: UNCOVERING UNFAMILIAR POSTOPERATIVE LVAD COMPLICATIONS

1DO, Loyola University Medical Center, Maywood, IL 2Loyola University Medical Center, Maywood, IL 3N/A, Maywood, IL

Matrix Metalloproteinases and Their Inhibitors and Proteoglycan 4 in Patients Undergoing Total Joint Arthroplasty.

Osteoarthritis, a degenerative disease of the joints, is the most common form of arthritis in the knee. Total joint arthoplasty is a commonly used treatment for joint degeneration and osteoarthritis, and due to these factors, TJA for hip and knee joints is projected to grow by 137% and 601% between 2005 and 2030. Matrix metalloproteases are enzymes found in the extracellular matrix that cleave matrix components. Normally MMPs are downregulated in tissues by Tissue Inhibitors of Metalloproteases, or TIMPs. The relative concentration of TIMPs also may denote some of the activity of the MMPs found in serum. Lubricin (proteoglycan 4) is a molecule found in the synovial fluid that protects joints by dissipating strain energy during locomotion. Lubricin synovial fluid concentration is also diminished in many patients with osteoarthritis, but not all. Given the importance of these three sets of molecules, our lab investigated the correlation between circulating lubricin, MMP levels and TIMPs levels. Blood plasma samples were obtained from de-identified subjects undergoing total joint arthroplasty at Loyola University Medical Center and the University of Utah. Normal blood plasma from pooled healthy individuals served as a control. We analyzed biomarker levels in plasma using ELISA. Our data show that MMP-1 and 9 were increased in TJA patients compared to normal controls, while MMP-2 and 13 were decreased. We also found decreased lubricin and tissue factor in surgical patients relative to controls. These data support the idea that lubricin is vital in protecting the synovial joint and that MMPs play a complex role in the destruction of the joint.

Abstract 17293: Functional Outcomes After Acute Pulmonary Embolism

Introduction: Pulmonary embolism (PE) is associated with significant acute morbidity, mortality, and long term functional limitations. There is paucity of data on acute and short term functional assessment after acute PE. Hypothesis: Functional capacity will improve from baseline to follow up among patients with acute PE. Methods: We prospectively analyzed patients who underwent evaluation by the pulmonary embolism response team (PERT) at Loyola University Medical Center between 2016 and 2018. We included patients with acute PE who underwent six-minute walk test (6MWT) at discharge and during outpatient follow up (50±72 days post discharge). We collected demographic and clinical characteristics. We used paired sampled t-test to compare continuous variables. Results: Among the 204 patients evaluated by PERT, 38 patients (18.6%) underwent 6MWT at baseline and follow up. Patients were classified as low risk (6 patients), submassive (29 patients), and massive (3 patients). Mean age was 61.3±14.2, 50% were female, 60.5% were white, 26.3% were black, 29% had cancer, and 68.4% had concomitant DVT, mean BMI 36.4±10.3, and mean PESI score was 96.8+44.4. Overall the mean 6MWT distance increased significantly from a baseline of 726.9±73.7 feet to 1042±72.8 feet at follow up (p&lt;0.001). Low risk (786±204 to 1115.8+177.6 p=0.63), Submassive (700.2±85 to 995.6±82.8 p&lt;0.001), and Massive PE (859±261.7 to 1343.3±307 p=0.168) groups all demonstrated improvement in 6MWT distance. Conclusions: Functional capacity as measured by 6MWT significantly improved during follow up after acute PE. Future studies are needed to determine predictors of favorable functional outcome and best treatment strategies.

Effect of Enoxaparin on Bleeding and Thrombosis in Patients Supported with Ventricular Assist Devices

Introduction There is limited literature evaluating the safety of enoxaparin use in patients supported by a ventricular assist device (VAD). The purpose of this study is to evaluate the incidence of bleeding and thrombosis in continuous flow VAD patients bridged with enoxaparin. Hypothesis Use of enoxaparin for bridging in VAD patients will not increase the incidence of major bleeding or thrombotic events (TE) compared to patients who never receive enoxaparin. Methods This was a retrospective cohort study of 198 patients implanted with continuous flow VADs (73% HeartMate II, 27% HVAD) at Loyola University Medical Center between December 2011 and December 2016. Patients were stratified into two groups: those who received bridging with enoxaparin (enoxaparin-bridge, n=74 [37%]) and those who did not (no enoxaparin-bridge, n=124 [63%]). The co-primary outcomes were (1) incidence of major bleeding requiring hospitalization and (2) incidence of TE, defined as hospitalization for VAD pump thrombosis or ischemic stroke. The secondary outcome was major bleeding occurring within seven days of enoxaparin administration. Results Baseline characteristics were similar between the two groups except for a higher rate of concomitant dipyridamole use in the enoxaparin-bridge group (37% vs 23%, p Conclusions VAD patients who received enoxaparin bridging for subtherapeutic INRs were not at an increased risk of major bleeding; however, they did have an increased rate of TE. The significance/causality of the latter remains unclear, as subtherapeutic INRs necessitating bridging may have contributed to an increased risk of clot formation independent of enoxaparin exposure. Prospective studies are needed to confirm these findings.

Tu1890 - Infectious and Genetic Characteristics of Clinical Eaepostive Enteropathogenic E. Coli (EPEC) Samples Identified by Biofire GI Panel at Loyola University Medical Center, Maywood, IL

Tu1890 - Infectious and Genetic Characteristics of Clinical Eaepostive Enteropathogenic E. Coli (EPEC) Samples Identified by Biofire GI Panel at Loyola University Medical Center, Maywood, IL

Relative Neutralization of Heparin from Different Origins by Protamine, Polybrene, Platelet Factor 4, and synthetic heparin antagonist PMX

IntroductionHeparin is the most widely used anticoagulant, which is derived from mammalian tissues. While porcine mucosal heparin is most commonly used clinically, sheep mucosal heparin and bovine mucosal heparin are also currently developed. Protamine Sulfate is the most commonly used antagonist of heparin, which is used clinically. Platelet Factor 4 is a platelet‐derived protein which is capable of neutralizing heparin endogenously. Polybrene and PMX are synthetic agents which can neutralize heparin. These agents are not used clinically. The purpose of this study is to compare the neutralization profile of various heparins by protamine and other heparin‐neutralizing agents.Materials and methodPorcine heparin was obtained from Medefill Inc. (Glendale Heights, IL). Bovine Heparins were obtained from Extrasul (Sao Paolo, Brazil). Ovine Heparin was obtained from Ronssi Co. (Souzhou, China). Protamine sulfate was obtained from Sanofi Avantis Co. (Paris, France). Platelet Factor 4 was obtained from Enzyme Research (South Bend, IN). Polybrene and PMX were of synthetic origin. Pool‐citrated plasma was obtained from Loyola University Medical Center Blood Bank. Blood‐clotting tests were performed using aPPT and TT reagents. Chromogenic substrate assays were carried out on the ACL‐Elite instrument. Plasma samples were supplemented with each of the pooled heparin preparations at a concentration of 0–10 mg/ml. Protamine neutralization studies were carried out at a fixed concentration of 10 mg/ml. Neutralization profiles were determined graphically and by calculating percent neutralization at a fixed concentration of 5 mg/ml.ResultsAt 5 ug/ml the protamine, the neutralization index for the different heparins were comparable in the TT, anti‐Xa and anti‐IIa assays (&gt; 90%) however in the APTT it was around 75% for porcine and bovine pool and 66% for ovine pool. In the polybrene neutralization the all heparins comparable neutralization index in the APTT (&gt;80%), TT (&gt;90%) and anti‐IIa (&gt;90%) however in the anti‐Xa the porcine and bovine were greater than 80% and bovine pool was greater than 90%.ConclusionsProtamine sulfate was found to be the most effective neutralizing agent for the bovine, ovine and porcine heparins. Assay based variations were noted in the neutralization profiles. With polybrene and platelet factor 4. These studies suggest that titration with the heparin neutralizing agent may be useful in demonstration the biosimilarities of heparins obtained from different sources.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Biomarkers of Inflammation, Thrombogenesis, and Collagen Turnover in Patients With Atrial Fibrillation.

The purpose of this study was to determine whether there are any differences in the levels of inflammatory, thrombotic, and collagen turnover biomarkers between individuals with atrial fibrillation (AF) and healthy volunteers. Circulating plasma levels of plasminogen activator inhibitor 1 (PAI-1), CD40-ligand (CD40-L), nucleosomes (which are indicators of cell death), C-reactive protein (CRP), procollagen III N-terminal propeptide (PIIINP), procollagen III C-terminal propeptide (PIIICP), procollagen I N-terminal propeptide, tissue plasminogen activator, and von Willebrand factor were analyzed as potential biomarkers of AF. Baseline plasma was collected from patients with AF prior to ablation surgery at Loyola University Medical Center. Individuals with AF had statistically significantly increased levels of PAI-1, CD40-L, and nucleosomes, when compared to the normal population (P < .0001). Additionally, there was a statistically significant increase in the CRP (P = .01), PIIINP (P = .04), and PIIICP (P = .0008) when compared to normal individuals. From this study, it is concluded that the prothrombotic, inflammatory, and collagen turnover biomarkers PAI-1, CD40-L, nucleosomes, CRP, PIIICP, and PIIINP are elevated in AF.

Role of stereotactic body radiation therapy in patients with hepatocellular carcinoma extensively pretreated with transarterial chemoembolization or yttrium-90.

233 Background: Hepatocellular carcinoma (HCC) is an aggressive disease with dismal outcomes. Patients who are not surgical candidates are routinely treated with local therapies such as TACE, Y90, or SRBT among others. The study aimed to assess treatment response and treatment related toxicity to SBRT in patients who received prior TACE or Y90 at our institution, some of whom subsequently underwent orthotopic liver transplantation. Methods: IRB approval was obtained to retrospectively review 26 medical records of patients who received SBRT at the Loyola University Medical Center from 9/9/14-12/28/16. GI toxicities were analyzed using the Common Terminology Criteria for Adverse Events (CTAE) version 4.0 following SBRT. Skin, pharyngeal/esophageal, thorax, lung, GU, and GI toxicities were included in toxicity analysis. Patients received radiation dose from 36 Gy - 50 Gy in 5 fractions using RTOG 1112 dose constraints for dosimetric plan evaluation. Fisher’s exact tests and Wilcoxon Rank Sum tests were used for statistical analysis. Results: Of the 26 patients, 21 patients had prior TACE (median 3 TACE procedures; ranging from 1-5). 6 patients had prior Y90 with or without prior TACE. Median follow up for the cohort was 51 weeks. No patient showed GI toxicities above grade 1 during SBRT, with fatigue and nausea being the most common. One patient who previously received Y90 developed fatal duodenal perforation. Pathology demonstrated this was related to tumor infiltration of the duodenum and was not related to post radiation necrosis. 6 patients went on to undergo OLT with all patients having treatment response on surgical pathology with 4 patients having complete treatment response. Conclusions: SBRT was shown to safely treat patients after prior therapies including Y90 and TACE. Furthermore, SBRT showed favorable outcomes in post-OLT patients. To our knowledge, this is the first study to assess the effects of SBRT following extensive local therapies for HCC including Y90. Prospective data is needed to evaluate these findings further with longer follow up.

Antibiotic prophylaxis and infection prevention for endoscopic endonasal skull base surgery: Our protocol, results, and review of the literature

Endoscopic endonasal approaches to the skull base provide minimally invasive corridors to intracranial lesions; however, enthusiasm for this new approach is always tempered by the recognition that this route requires passage through a nonsterile sinonasal corridor. Despite an increasing number of patients undergoing these surgeries, there remains no consensus on the use of perioperative antibiotics. A retrospective review of consecutive patients undergoing endoscopic endonasal skull base surgery (EESBS) at Loyola University Medical Center by the same neurosurgeon and otolaryngologist team between February 2015 and October 2016 was performed. Antibiotic regimens, presence of an intraoperative or postoperative cerebrospinal fluid (CSF) leak, dural reconstruction method, and rates of sinusitis, meningitis, and/or intracranial abscess were analyzed. 39 patients who underwent a total of 41 EESBSs with a mean age of 46 years were identified. A vascularized nasoseptal flap was used for dural reconstruction when high flow CSF leaks were encountered intraoperatively (n = 17); otherwise, reconstruction mostly consisted of allografts and/or free mucosal grafts. There were zero postoperative cases of CSF leaks, meningitis, or intracranial infection. Our current antibiotic prophylaxis protocol coupled with the use of variable dural reconstruction techniques dictated by intraoperative findings has led to low rates of postoperative CSF leaks, intracranial infections, and meningitis. A survey was also distributed to Neurological Surgery Residency Programs to gain a better understanding of the EESBS protocols that are being used nationally. The practice of antibiotic prophylaxis for patients undergoing EESBS is quite variable and this study should provide the impetus for multi-institutional comparison studies.

Clinical Characteristics of Diarrheal Illness with Enteropathogenic E. coli (EPEC) Diagnosed with FilmArray (BioFire Diagnostics, Salt Lake City, UT) Multiplex PCR (MPCR) Testing. Maria Georgen BS, Paul Schreckenberger, PhD, Paul O’Keefe MD. Loyola University Medical Center, Maywood, Illinois, USA

BackgroundEPEC is a known cause of diarrhea, predominately in children, which has not been identified with conventional stool culture in most medical centers. MPCR testing assesses stool samples in which DNA targets for 20 or more pathogens are tested with rapid turnaround. This method has become the standard for diagnostic testing in many clinical laboratories. MPCR testing has identified EPEC as among the most frequent pathogens in published studies.MethodsWe have completed a retrospective review of medical records of patients who tested positive for EPEC in our medical center.ResultsEPEC was found in 56 of 332 MPCR samples analyzed between February 1, 2016 and July 31, 2016. EPEC was the only pathogen in 25 while co-infecting pathogens were found in 31. Co-infections included other diarrhea-causing E. coli (ETEC, EAEC and EIEC but none with STEC) in 17, C. difficile in 7, viruses (astrovirus 3, sapovirus 2, norovirus 2, rotavirus 2), Campylobacter 3, Giardia 2, Salmonella 2, Pleisiomonas 1 and Yersinia 1.Patients ages ranged from <1 to 100 with 37 over age 19. Half were female. 7/46 had received antibiotic prior to sample collection. 10 reported recent travel. 51/52 presented to the emergency department, urgent care centers or ambulatory clinics. Symptoms included fever in 15/54, nausea 16/54, vomiting 14/54 and abdominal pain in 17/56. Diarrhea was described as watery in 23/32 and bloody in only 3. Antibiotic treatment was prescribed for 6/24 with EPEC only and for 22/31 with coinfection. A follow-up encounter was documented for 24 patients with EPEC only: 13 resolved, 3 remained ill and 8 could not be assessed.ConclusionEPEC is frequently found in stools from persons with diarrhea when MPCR is employed. Symptoms cannot be attributed to EPEC alone when other pathogens are found, but our analysis does suggest that EPEC is a common cause of diarrheal illness in adults as well as children. Prospective studies on natural history and treatment are necessary.Disclosures All authors: No reported disclosures.

328 Outcome Analysis of Common Peroneal Nerve Neuroplasty at Lateral Fibular Neck

Abstract INTRODUCTION Common Peroneal Nerve (CPN) neuropathy is the most common entrapment neuropathy of the lower extremities. Patients present with sensory loss along the anterolateral leg and dorsum of the foot, or weakness of the foot dorsiflexors and evertors. METHODS This is an IRB-approved retrospective review of a prospectively maintained database of patients who underwent decompressive surgery for CPN neuropathy with a minimum of 3 months follow up at Loyola University Medical Center. Motor scores were totaled using the Oxford Scale, with an improvement defined as resolution of pain or sensory loss or improvement in motor score by at least a 1-grade. RESULTS &gt;30 patients were analyzed. Of the 26 patients who presented with abnormal lower extremity motor scores, 24 had at least 1 grade improvement in motor scores, and 2 experienced no change. 26 patients presented with lower extremity decreased sensation, and 12 of these patients reported improved sensation, while 14 patients reported no change. Patients with an increased time to surgery (&gt;67 weeks) had a non-significant trend towards worse outcomes (p = .06). Patients who presented with weakness had a significant trend towards improvement (p = .0006) compared to patients presenting with pain and sensory deficits. CONCLUSION Surgical decompression of the CPN at the lateral fibular neck is an effective and safe procedure. Patients presenting with pain or sensory loss did not show a significant trend towards improvement with surgery, while patients presenting with motor deficits had a significant improvement with surgery. There was a trend of worse outcomes with a symptoms-to-surgery time greater than 67 weeks.

Identification of Preoperative and Intraoperative Risk Factors for Complications in the Elderly Undergoing Elective Craniotomy.

Neurosurgical patients are aging as the general population is becoming older. A retrospective review of patients ≥65 years of age who underwent an elective craniotomy from 2007 to 2015 to identify risk factors for 30-day morbidity/mortality was conducted. Key preoperative variables included age, comorbidities, and functional status based on the Karnofsky Performance Status score and modified Rankin Scale score. Outcome variables included long-term care (LTC) complications, neurologic complications, systemic/infectious complications, length of stay, functional outcomes, and mortality. A total of 286 patients ≥65 years underwent elective craniotomy at Loyola University Medical Center over 8 years. Seventy-two patients had a preoperative neurologic deficit and 95 had a systemic morbidity before surgery. Postoperative neurologic and systemic morbidity was 14% and 23%, respectively. 7% of patients experienced a LTC complication and 5 patients (1.7%) died. Worse preoperative scores on both the Karnofsky Performance Status and modified Rankin Scale predicted increased length of stay and mortality (P < 0.05). Univariable and multivariable analyses showed that patients with preoperative motor deficit, altered mental status, congestive heart failure, smoking history, and chronic steroid use were all more likely to have an LTC complication, and increased anesthesia time and estimated blood loss increased risk for LTC, neurologic, and systemic/infectious complications. This study identifies factors that predict perioperative complications for elderly patients undergoing elective craniotomies, particularly congestive heart failure, smoking history, chronic steroid use, anesthesia time, and estimated blood loss. Age alone should not preclude elective craniotomy.

Allogeneic hematopoietic stem cell transplantation for mantle cell lymphoma in a heavily pretreated patient population.

7558 Background: Allogeneic hematopoietic stem cell transplantation (allo-SCT) is the only potential curative treatment option for patients with MCL due to its potent graft-versus-lymphoma (GVL) effect. Survival following allo-SCT for MCL is variable due to high rates of non-relapse mortality (NRM). Methods: We retrospectively identified all patients who were treated with an allo-SCT for MCL at Loyola University Medical Center between January 1, 1999 and January 1, 2016. Probability estimates for overall survival (OS) and non-relapse mortality (NRM) at 5 years were calculated from the date of allo-SCT to the date of patient death or last known follow-up. Significance was determined using a cox proportional hazard (CPH) model. Rates of acute graft-versus-host disease (aGVHD) and relapse were also reported. Results: Patient characteristics (n = 29) are listed in Table. Median follow-up in surviving patients is 10 years (range 5-14 years). A majority of patients (n = 23, 79%) had 3 or more lines of treatment prior to allo-SCT. The 5 year rates of OS and NRM for all patients are 42% and 53%, respectively. Univariate analysis showed a lower risk of death in patients who received TBI-based conditioning (HR: 0.19, 95 CI: 0.04 – 0.81, p = 0.03), and those who had HLA-matched related donor (MRD) transplants (HR: 0.29, 95 CI: 0.11 – 0.79, p = 0.02). Patients who received more than 3 lines of prior treatment had a higher risk of death (HR: 2.77, 95% CI: 1.05-7.34, p = 0.04). Low rates of grade III/IV aGVHD (n = 4) and relapse (n = 4) occurred in our patient population. Two patient deaths were attributable to aGVHD, and the majority of other deaths were due to treatment-related toxicities. Conclusions: In an era of numerous effective non-curative salvage therapies, the optimal timing of allo-SCT for MCL needs further clarification. Our data supports early opposed to delayed allo-SCT for select high-risk patients with MCL who have a MRD. [Table: see text]

Infliximab and Low Dose Alemtuzumab in Patients with Steroid-Refractory Acute Graft-Versus-Host Disease

Introduction:Steroid-refractory grade IV acute graft-versus-host disease (aGVHD) after allogeneic hematopoietic stem cell transplantation (HSCT) carries a mortality rate of approximately 80%. Trials of novel therapies including antibodies directed against the T-cell immune response have generally failed to improve outcomes although may lead to responses. Infliximab, a chimeric monoclonal antibody to TNF alpha, and alemtuzumab another monoclonal antibody targeting CD52, an antigen expressed on T and B lymphocytes and other antigen presenting cells (APCs) both have produced response rates in the 50-75% range. However, few are long-term survivors as the majority die of opportunistic infections (OI). While steroids are ineffective in many series, they are continued when novel agents are employed. We have approached steroid-refractory aGVHD with a combination of rapid steroid discontinuation, standard doses of infliximab and short course low dose alemtuzumab with the hope for aGVHD control without early deaths from OIs.Methods:We identified all patients who were treated for steroid-refractory aGVHD between January 1, 2014 and March 1, 2016 at Loyola University Medical Center. The diagnosis of aGVHD was made by clinical criteria per the National Institutes of Health guidelines. The diagnosis was confirmed by endoscopic evaluation and biopsy of the affected organ. All patients received methylprednisolone 2 mg/kg/day IV given in twice daily dosing for at least 7 days prior to being considered steroid-refractory. Patients received infliximab 10 mg/kg IV infusion weekly x 2 then every other week until remission and alemtuzumab 3 mg IV test dose on day 1, followed by 10 mg IV daily for 4 days. At the same time steroids were reduced by 50% and further reductions of 50% were made every 4 days. Responses were assessed by daily grading of aGVHD per Glucksberg criteria after dosing of infliximab and alemtuzumab. A complete response (CR) was defined as full resolution of abdominal pain, diarrhea, rectal bleeding, liver function test abnormalities, or skin involvement. A partial response (PR) was defined as a 50% improvement in diarrhea, liver function abnormalities, or skin involvement with a decrease in 1 or more grade levels of aGVHD per Glucksberg criteria.Results:To date 6 patients have been treated for steroid-refractory aGVHD after matched related donor (MRD) or matched unrelated donor (MUD) HSCT. Patient characteristics are shown in Table 1. There were 5 patients who underwent a MRD or MUD HSCT for myelodysplastic syndrome (MDS), and 1 patient who underwent a MUD HSCT for B-cell acute lymphoblastic leukemia (B-ALL). Median age at treatment was 64 years. All patients had Glucksberg grade 4 aGVHD (Table 1). The overall response rate (ORR) was 83% with 4 patients achieving a PR, 1 patient achieving CR, and 1 patient with no response to treatment. Day 100 survival after dosing of alemtuzumab was 50% with deaths due to aGVHD in 2 patients and death due to septic shock in 1 patient. CMV reactivation occurred in 4 patients and EBV reactivation occurred in 1 patient.Conclusion:In our single institution analysis, the combination of infliximab and alemtuzumab with rapid steroid withdrawal achieved a high ORR of 83% in treatment of steroid-refractory aGVHD after MRD or MUD HSCT with an encouraging 50% survival at day 100. This approach will be continued to further define its efficacy and safety for the treatment of steroid-refractory aGVHD. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Persistent Prothrombotic State in Atrial Fibrillation Despite Use of Novel Oral Anti-Coagulants

Background: Oral anticoagulants such as warfarin have been conventionally used for the management of atrial fibrillation (AF). Despite the effectiveness of warfarin, its use in AF patients requiring anticoagulation is suboptimal with an even greater underuse seen in elderly patients who are at higher risk of stroke. New oral anticoagulants such as rivaroxaban(R), apixaban (A), dabigitran (D) and edoxaban (E) have been approved to manage thrombotic and cardiovascular disorders including AF. The newer anticoagulants do not require continuous monitoring like warfarin and are much more convenient for patients with AF.Objective: To profile the baseline level of circulating thrombotic biomarkers plasminogen activator inhibitor (PAI-1), von Willebrand Factor (vWF), microparticle bound tissue factor (MP-TF) and prothrombin fragment 1.2 (F1.2) in patients with AF. Additionally, the effect of novel oral anticoagulants (R, A, D and E) on the levels of thrombotic biomarkers in patients with AF is assessed.Materials and Methods: Citrated blood samples were drawn from 30 patients (21 male and 9 female; mean age 59.1) prior to ablation surgery for AF at Loyola University Medical Center in Maywood, Illinois. Citrated blood was spun at 3000 rpm to obtain platelet poor plasma. Normal plasma samples from healthy controls (24 male and 24 female; mean age 33) were purchased from a commercial source (George King Biomedical, Overland Park, KS). The plasma samples were analyzed using a biochip array (Randox, London, UK) for metabolic syndrome biomarkers including PAI-1 and ELISA kits for vWF, MP-TF (Hyphen BioMed, Nueville-Sur-Oise, France) and prothrombin F1.2 (Siemens, Newark, DE).Results: Compared to the control group, circulating levels of vWF, MP-TF and PAI-1 were statistically increased in patients with AF (P<0.0001, P<0.0001, and P=0.0014, respectively). Circulating levels of prothrombin F1.2 showed no difference between the AF and the control group (P=0.2696). AF patients (n=30) were divided into two groups based on their usage (Group 1, n=17) and non-usage (Group 2, n=10) of any novel oral anticoagulant (R, A, D and E). Three patients on warfarin were excluded from this section of data analysis. A statistical increase in vWF (P=0.0018) and MP-TF (P=0.0039) remained in those taking novel oral anticoagulants compared to group 2. No difference was seen in PAI-1 (P=0.333) or F1.2 (P=0.31) between groups 1 and 2. Percent change from the normal mean was also calculated for PAI-1, vWF, MP-TF and F1.2 in group 1 (78%, 61.1%, 142%, 8.9%, respectively) and group 2 (113.6%, 16.9%, 31.7%, 41.4%, respectively) as seen in table 1.Discussion: Elevated levels of PAI-1, vWF and MP-TF seen in AF patients compared to normal provide insight into an additional risk of thrombogenesis associated with AF which is not targeted by current anticoagulant medications. Most AF patients are assessed using a stroke risk stratification scale (CHA2DS2VASc) to determine if anti-coagulants should be used to prevent stroke associated with AF. Patients in group 1 had a mean CHA2DS2VASc score of 1.15 compared to 2.18 see in group 2. This data supports studies which suggest that including levels of prothrombotic biomarkers to current risk stratification scales could be more effective in assessing the risk of stroke of patients with AF. This data also suggests that although very effective in lowering prothrombin F1.2 levels in AF, the newer anticoagulants, R,A,D and E still leave additional prothrombotic biomarkers unaffected. These unaffected biomarkers could be the potential target of future drug therapies which could lower the risk of stroke in patients with AF even more than the use of newer anticoagulants alone. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Pain Management of the Burn Patient

Dr. Patel is Resident, CA3, Department of Anesthesiology, Loyola University Medical Center, 2160 S 1st Ave, Maywood, IL 60153; E-mail: [email protected]. The author and all staff in a position to control the content of this CME activity have disclosed that they and their spouses/life partners (if any) have no financial relationships with, or financial interests in, any commercial companies pertaining to this educational activity.The author has disclosed that the use of Diphoterine as discussed in this article has not been approved by the U.S. Food and Drug Administration. Please consult the product labeling for approved uses.CME AccreditationLippincott Continuing Medical Education Institute, Inc., is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.Lippincott Continuing Medical Education Institute, Inc., designates this enduring material for a maximum of 1.5 AMA PRA Category 1 Credits™. Physicians should only claim credit commensurate with the extent of their participation in the activity. To earn CME credit, you must read the CME article and complete the quiz and evaluation assessment survey on the enclosed form, answering at least 70% of the quiz questions correctly. This CME activity expires on November 30, 2017.CNE AccreditationLippincott Williams & Wilkins is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center's Commission on Accreditation. LWW, publisher of Topics in Pain Management, will award 2.0 contact hours for this continuing nursing education activity. This activity has been assigned 1.0 pharmacology credits. Instructions for earning ANCC contact hours are included on page 11 of the newsletter. This CNE activity expires on December 31, 2018.