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Abstract Abstract 3803 Background: The MMRC is a non-profit, disease-focused consortium founded in 2004 comprised of 13 North American centers with expertise in multiple myeloma (MM). The MMRC Inc. (Norwalk, CT), MMRC's member institutions, and several pharmaceutical partners work closely to speed early development of new treatment options for MM patients. In December 2007, MMRC headquarters staff implemented multiple project management (PM) business solutions to address trial barriers that delay activation of our phase I-II clinical trials and established trial metric benchmarks considered attainable at our member institutions. In November 2009, we reported initial data1 on trial activation: MMRC trials initiated between Sep08-Jul09 (n=5) demonstrated a 38% decrease in mean time to first patient dosed (FPFD), compared with the Early Group trials (EG) initiated before PM solutions (Jun06-Sept08; n=7 trials). These results also confirmed improvement over published metrics from Dilts et al 2,3. We present additional data on time to FPFD and now enrollment, to assess impact of the MMRC PM resources and processes on trial efficiency. Methods: Twenty-one (21) trials conducted within the MMRC from May 2006 to June 2010 had sufficient trial data for review. Data were collected by MMRC-funded project managers at the clinical centers using a web-based clinical trial management system (CTMS). FPFD was defined as the time from the member institutions' receipt of the final protocol (FP) from the trial sponsor, to the time the first patient was dosed on the trial at any participating MMRC member institution. With respect to enrollment, pre-study enrollment commitment (EC) established between MMRC and the study sponsor was defined as the total number of subjects committed to receive at least one dose of study drug across all participating MMRC centers on a trial; baseline enrollment timeline (BET) was prospectively defined as the target time period to attain EC. Results: Mean time to FPFD was 181 calendar days for the early group trials (EG, n=7) and 122 days for the recent group (RG) trials (n=14, Sep08 – Jun10), representing a 32% reduction of time to FPFD in the RG. Additionally, time from final protocol to first patient dosed at all MMRC centers on a trial decreased 18% from a mean of 7.7 months (EG) to 6.3 months (RG). With respect to MMRC trial enrollment, data was available for 16/21 trials (5 EG and 11 RG). 2 EG trials were missing data and 3 RG trials were still enrolling as of June 2010. The mean MMRC pre-study EC was 39 subjects per trial (n=16 trials; 626 enrollment target); the mean actual MMRC enrollment was 49 subjects per trial (n=16; 783 enrolled through Jun 29, 2010) representing a 25% increase in actual versus committed enrollment. Two trials did not meet MMRC EC: MMRC investigators discontinued their involvement in these trials at approximately 30% target EC due to trial complexity or low patient enrollment. 14/16 evaluable trials (88%) met their EC; 11/16 trials met EC within BET (69%) of which 8/16 trials (50%) reached EC 34% faster than their BET (representing a mean reduction of 4.5 months). The overall pre-study mean BET for 16 trials was 13.1 months. MMRC's actual mean enrollment timeline was 11.3 months for the group of 14 evaluable trials representing improvement over the original BET by a mean of 1.9 months (14%). We believe FP to FPFD is a more meaningful metric beyond that of first patient consented. Moreover, we believe that if all participating trial centers focus their efforts on dosing the first patient and within a targeted timeframe, it may improve our research efforts overall. Conclusion: Development of drugs in the clinical setting has become time and resource intensive. Activating and enrolling trials promptly is a priority for drug development. The MMRC's standardization of processes and support for site-based PM resources results in improved trial metrics. MMRC member centers met or exceeded pre-specified enrollment targets in 88% of the trials analyzed to date. Ongoing monitoring of trial conduct continues to reveal areas where increased focus is needed to realize further trial efficiencies. These trial metrics and measures to improve efficiency may be applied with similar expected benefit in all oncology disciplines. Disclosures: Wear: Multiple Myeloma Research Consortium (MMRC): Employment. Richardson:Multiple Myeloma Research Consortium (MMRC): Member Institution of the MMRC; Millennium: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Johnson & Johnson: Membership on an entity's Board of Directors or advisory committees. Revta:Multiple Myeloma Research Consortium (MMRC): Member Institution of the MMRC. Vij:Multiple Myeloma Research Consortium (MMRC): Research Funding; Multiple Myeloma Research Consortium (MMRC): Member Institution of the MMRC. Fiala:Multiple Myeloma Research Consortium (MMRC): Member Institution of the MMRC. Lonial:Bristo-Myers Squibb: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene Corporation: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Millenium Pharmaceuticals Inc: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Onyx: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding. Francis:Multiple Myeloma Research Consortium (MMRC): Member Institution of the MMRC. Siegel:Multiple Myeloma Research Consortium (MMRC): Member Institution of the MMRC; Celgene: Speakers Bureau; Millennium: Speakers Bureau. Schramm:Multiple Myeloma Research Consortium (MMRC): Member Institution of the MMRC. Jakubowiak:Multiple Myeloma Research Consortium (MMRC): Member Institution of the MMRC, Research Funding; Millennium: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Honoraria, Speakers Bureau; Centocor Ortho-Biotech: Honoraria, Speakers Bureau; Exelixis: Honoraria, Speakers Bureau; Bristol-Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Harvey:Multiple Myeloma Research Consortium (MMRC): Member Institution of the MMRC. Reece:Multiple Myeloma Research Consortium (MMRC): Member Institution of the MMRC; Celgene: Honoraria, Research Funding; Ortho Biotech: Honoraria, Research Funding; Merck: Honoraria, Research Funding; Amgen: Honoraria, Research Funding; Facet: Research Funding; Otsuka: Honoraria, Research Funding. Gul:Multiple Myeloma Research Consortium (MMRC): Member Institution of the MMRC. Jagannath:Celgene: Honoraria; Millenium: Honoraria; Orthobiotec: Honoraria; Onyx Pharma: Honoraria; Merck: Honoraria; Proteolix: Honoraria; Multiple Myeloma Research Consortium (MMRC): Member Institution of the MMRC. La:Multiple Myeloma Research Consortium (MMRC): Member Institution of the MMRC. Hofmeister:Multiple Myeloma Research Consortium (MMRC): Member Institution of the MMRC. Jansak:Multiple Myeloma Research Consortium (MMRC): Member Institution of the MMRC. Stewart:Millennium: Consultancy; Celgene: Honoraria; Multiple Myeloma Research Consortium: Member Institution of the MMRC. Hagerty:Mayo Clinic: Employment; Multiple Myeloma Research Consortium (MMRC): Member Institution of the MMRC. Wolf:Multiple Myeloma Research Consortium (MMRC): Member Institution of the MMRC; Celgene: Speakers Bureau; Millennium: Speakers Bureau; Novartis: Speakers Bureau; Orthobiotech: Speakers Bureau. Davis:Multiple Myeloma Research Consortium (MMRC): Member Institution of the MMRC. Krishnan:Celgene: Speakers Bureau; Multiple Myeloma Research Consortium (MMRC): Member Institution of the MMRC. Duarte:Multiple Myeloma Research Consortium (MMRC): Member Institution of the MMRC. Zimmerman:Millennium, Celgene: Speakers Bureau. Cisneros:Multiple Myeloma Research Consortium (MMRC): Member Institution of the MMRC. Kumar:Celgene: Consultancy, Research Funding; Millennium: Research Funding; Merck: Consultancy, Research Funding; Novartis: Research Funding; Genzyme: Consultancy, Research Funding; Cephalon: Research Funding; Bayer: Research Funding; Multiple Myeloma Research Consortium: Member Institution of the MMRC. Birgin:Multiple Myeloma Research Consortium (MMRC): Member Institution of the MMRC. Ott:Multiple Myeloma Research Consortium (MMRC): Employment. Tasca:Multiple Myeloma Research Consortium (MMRC): Employment. Kelley:Multiple Myeloma Research Consortium (MMRC): Employment. Anderson:Millennium: Consultancy; Multiple Myeloma Research Consortium (MMRC): Member Institution of the MMRC; Celgene: Consultancy; Novartis: Consultancy; Onyx: Consultancy; Merck: Consultancy; Bristol-Myers Squibb: Consultancy; Acetylon: Equity Ownership, Membership on an entity's Board of Directors or advisory committees. Giusti:Multiple Myeloma Research Consortium (MMRC): Employment.

Abstract BACKGROUND: The study of rare diseases is limited by the uncommon nature of the conditions as well as the widely dispersed patient populations. Current rare disease registries such as the National Organization of Rare Diseases utilize centralized platforms for data collection; however because of their broad nature, these do not always capture unique, disease specific elements. Hairy Cell Leukemia (HCL) is a rare leukemia globally with approximately 900 new cases diagnosed in the US each year. The HCL Foundation undertook creation of a Patient Data Registry that collects data from multiple HCL Centers of Excellence (COE) around the globe to better understand the complications, treatment outcomes, disease subtypes, comorbid conditions, epidemiology, and quality of life of patients with HCL. METHODS: Investigators at The Ohio State University Department of Biomedical Informatics and Division of Hematology in collaboration with the HCL Foundation developed a Patient Data Registry (PDR) for the longitudinal capture of high quality research data. This system differs from other registries in that it uses a federated( rather than centralized) architecture, wherein data is queried and integrated in an on-demand manner from local registry databases at each participating site. Further, the data collected for use in the registry combines both automated exports from existing electronic health records (EHRs) as well as additional data entered via a set of web-based forms. All manually entered data comes from source documents, and data provenance spanning electronic and manually entered data is maintained via multiple technical measures. Patients may be enrolled at HCL COE, or, if they do not have access to a COE they may enroll via a web-based portal (www.hairycellleukemia.org). At this time due to regulatory requirements the web-based portal is available to US patients only. All data are de-identified (see Figure 1: De-Identification Workflow) which reduces regulatory burden and increases opportunities for data access and re-use. End users have access to data via a project-specific query portal. RESULTS: The Patient Data Registry has been deployed at The Ohio State University, Royal Marsden Hospital, and MD Anderson Cancer Center, and is undergoing deployment at the University of Rochester. Up to 25 international HCL COE may participate. In addition, US patients are actively entering the registry via the web-based portal. To date, 227 patients have been consented to the registry with 119 of these being via the web-based entry point. CONCLUSION: We created an international and web-based patient data registry which will enable researchers to study outcomes in HCL in ways not previously possible given the rarity of the disease. This work was made possible by research funding from the Hairy Cell Leukemia Foundation. Figure De-Identification Workflow Figure. De-Identification Workflow Disclosures Andritsos: Hairy Cell Leukemia Foundation: Research Funding. Anghelina:Hairy Cell Leukemia Foundation: Research Funding. Lele:Hairy Cell Leukemia Foundation: Research Funding. Burger:Pharmacyclics: Research Funding. Delgado:Gilead: Consultancy, Honoraria; Novartis/GSK: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Roche: Consultancy, Honoraria, Research Funding; Infinity: Research Funding. Jones:AbbVie: Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Pharmacyclics, LLC, an AbbVie Company: Membership on an entity's Board of Directors or advisory committees, Research Funding. Lozanski:Beckman Coulter: Research Funding; Genentech: Research Funding; Stemline Therapeutics Inc.: Research Funding; Boehringer Ingelheim: Research Funding. Montserrat:Morphosys: Other: Expert Testimony; Vivia Biotech: Equity Ownership; Gilead: Consultancy, Other: Expert Testimony; Pharmacyclics: Consultancy; Janssen: Honoraria, Other: travel, accommodations, expenses. Parikh:Pharmacyclics: Honoraria, Research Funding. Park:Genentech/Roche: Research Funding; Amgen: Consultancy; Juno Therapeutics: Consultancy, Research Funding. Robak:Pharmacyclics, LLC, an AbbVie Company: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; AbbVie: Consultancy, Honoraria, Research Funding. Tam:janssen: Honoraria, Research Funding; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees; AbbVie: Honoraria, Membership on an entity's Board of Directors or advisory committees. Heckler:Hairy Cell Leukemia Foundation: Research Funding. Payne:Hairy Cell Leukemia Foundation: Research Funding.

Abstract BACKGROUND. The detection of minimal residual disease (MRD) at the level of 0.01%/10-4 or above is a strong independent predictor of reduced progression-free (PFS) and overall survival (OS) in patients with CLL treated with chemoimmunotherapy. Although newer agents such as B-cell receptor pathway inhibitors can result in prolonged survival without achieving complete response, there remains a important role for MRD analysis in assessing therapeutic strategies aimed at disease eradication and cure. This is particularly important in front-line trials for fit patients which now require at least five years of follow-up if PFS is used as an endpoint. The feasibility of using MRD as a surrogate or intermediate endpoint for accelerated approval of new treatments is under review by regulatory agencies but further prospective validation is required. At the same time technology is rapidly evolving and high-throughput sequencing (HTS) technologies now detect MRD at the 0.0001%/10-6 level. It is therefore important to determine the most effective approaches for quantifying MRD that are compatible with previous studies but sufficiently sensitive for current treatments. AIMS. This collaborative project had two objectives. First, to identify the simplest and most flexible flow cytometry panel capable of detecting MRD at the 0.01%/10-4 or lower, that is compatible with published data and independent of instrument/reagent manufacturer. Second, to compare the flow cytometry approach with HTS analysis using the ClonoSEQ assay (Adaptive Biotechnologies, Seattle, WA). METHODS AND RESULTS. A core panel of antibodies for MRD detection was identified by testing an 8-marker combination in 52 samples (27 post-treatment and 25 dilution study) and re-analysing data with serial exclusion of single markers to determine redundancy. A 1-tube core panel of CD19, CD20, CD5, CD43, CD79b, and CD81 was identified and validated against the previously published 2-tube 6-marker and 4-tube 4-marker ERIC panels in 76 samples (19 post-treatment and 57 dilution study). The results showed good concordance (for log-transformed data above the LoQ, linearity=0.977, Pearson correlation co-efficient=0.983, average difference=0.026 log, 95% limit of agreement 0.20log) and a limit of detection of 0.001%/10-5 for the 1-tube core panel. Inter-operator variation was similar to CML MRD monitoring with both experienced operators, or inexperienced cytometrists after ~1 hour of specific education, achieving a 95% limit of agreement less than 0.3log in samples with MRD levels ranging from 0.0001 – 100%. The flow cytometry approach was compared with the ClonoSEQ HTS assay in 109 samples (21 dilution study and 88 post-treatment samples, complete data currently available on 13/88). The assay was applicable to the vast majority CLL patients, often with two clonal markers. There was 94% concordance at the 0.01% (10-4) threshold (15 samples with ≥0.01% CLL by both methods, 14 samples with <0.01% by both methods, 1 sample with 0.03% CLL by HTS and <0.003% CLL by flow cytometry, and 1 sample with 0.005% CLL by HTS and 0.012% by flow cytometry. HTS detected CLL IGH sequences in 22% (7/31) samples with no detectable CLL cells by flow cytometry (i.e. CLL level 0.0001-0.001%, 3/13 patient samples and 4/18 dilution samples). HTS demonstrated a relatively high variability in quantification, as seen in previous studies, but with a clear superiority in the limit of detection and good linearity (linearity=0.905, Pearson correlation co-efficient=0.870, average difference=0.078 log, 95% limit of agreement 1.5 log). CONCLUSIONS. The 1-tube 6-marker flow cytometry core panel is compatible with published studies, manufacturer-independent and flexible, providing directly quantitative results to 0.001%/10-5 without requiring a pre-treatment sample. HTS requires further work to standardise the quantitative analysis and prospective validation but the ClonoSEQ assay is applicable to >95% of CLL patients, does not require viable cells and is extremely sensitive, detecting residual disease in a significant proportion of cases with <0.01% CLL. The results indicate that flow cytometry and HTS are complementary technologies with a combined approach offering the most reliable way of quantifying CLL at the 0.01%/10-4 threshold while allowing higher sensitivity in clinical trials aimed at disease eradication. Disclosures Rawstron: Roche: Honoraria; Biogen Idec: Consultancy; Gilead: Consultancy, Honoraria; Abbvie: Honoraria; BD Biosciences: Intrasure reagent Patents & Royalties; Celgene: Honoraria; GSK: Honoraria. Williamson:Adaptive Biotechnologies: Employment, Equity Ownership. Sanders:Adaptive Biotechnologies: Employment, Equity Ownership. Robins:Adaptive Biotechnologies: Consultancy, Equity Ownership, Patents & Royalties. Hallek:Celgene: Honoraria, Research Funding; Mundipharma: Honoraria, Research Funding; Roche: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; GSK: Honoraria; Gilead: Honoraria. Hillmen:Roche: Honoraria, Research Funding; GSK: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Pharmacyclics: Honoraria, Research Funding; Gilead: Honoraria, Research Funding.

INTRODUCTION: The association of Acute Pancreatitis and Celiac Disease (CD) has been sparingly reported in the literature. CD is known to affect approximately 1% of the western population. A Swedish national database study reported a 3-fold increased risk of developing pancreatitis in patients with CD. The exact mechanism of this is unknown, but it could be related to an untreated celiac disease affecting the major papilla causing stenosis or exocrine pancreatic insufficiency that has been reported previously. This study aimed to look at the association between acute pancreatitis and celiac disease. We also looked at whether there was any association between chronic pancreatitis and celiac disease. METHODS: We performed a retrospective cross-sectional cohort study using the 2013 National Inpatient Sample (NIS) database. We included all patients who were hospitalized with either acute pancreatitis (ICD Code 577.0) or Chronic Pancreatitis (577.1). Patients who had diagnoses of both acute and chronic pancreatitis were considered to have acute on chronic pancreatitis and combined with the chronic pancreatitis group. We then analyzed both groups for the presence or absence of celiac disease. Continuous variables were compared using t-tests, and categorical variables were compared using Rao-Scott chi-square tests. All analyses were performed using SAS Survey Procedures (version 9.4, The SAS Institute, Cary, NC). RESULTS: We analyzed more than 35 million hospitalizations in 2013 out of which 378,715 had a primary discharge diagnosis of acute pancreatitis and 155,130 had a primary discharge diagnosis of chronic pancreatitis. The mean age in the acute pancreatitis group was 53.3 yrs and in chronic pancreatitis group was 51.7 yrs. There were more males in chronic pancreatitis group (55.1%) than females (44.9%). There was significantly higher prevalence of acute pancreatitis in CD (2.3%) than non-CD patients (1.2%) (Figure 1, P = 0.001). Similarly, there was higher prevalence of chronic pancreatitis (1.2%) than the control group (0.43%) (Figure 1, P < 0.001). CONCLUSION: There is a higher prevalence of acute pancreatitis in patients with CD. Patients were also found to have much higher prevalence of chronic pancreatitis in CD. This could be related to recurrent acute pancreatitis episodes in CD patients. Further studies are needed to validate these findings.

INTRODUCTION: The association of Acute Pancreatitis and Celiac Disease (CD) has been sparingly reported in the literature. CD is known to affect approximately 1% of the western population. A Swedish national database study reported a 3-fold increased risk of developing pancreatitis in patients with CD. The exact mechanism of this is unknown but it could be related to untreated celiac disease affecting the major papilla causing stenosis or exocrine pancreatic insufficiency that has been reported previously. The aim of this study was to look at the association between acute pancreatitis and celiac disease. We also looked whether there was any association between chronic pancreatitis and celiac disease. METHODS: We performed a retrospective cross-sectional cohort study using the 2013 National Inpatient Sample (NIS) database. We included all patients who were hospitalized with either acute pancreatitis (ICD Code 577.0) or Chronic Pancreatitis (577.1). Patients who had diagnoses of both acute and chronic pancreatitis were considered to have acute on chronic pancreatitis and combined with the chronic pancreatitis group. We then analyzed both groups for presence or absence of celiac disease. Continuous variables were compared using t-tests and categorical variables were compared using Rao-Scott chi-square tests. All analyses were performed using SAS Survey Procedures (version 9.4, The SAS Institute, Cary, NC). RESULTS: We analyzed more than 35 million hospitalizations in 2013 out of which 378,715 had a primary discharge diagnosis of acute pancreatitis and 155,130 had a primary discharge diagnosis of chronic pancreatitis. The mean age in the acute pancreatitis group was 53.3 yrs and in chronic pancreatitis group was 51.7 yrs. There were more males in chronic pancreatitis group (55.1%) than females (44.9%). There was significantly higher prevalence of acute pancreatitis in CD (2.3%) than non-CD patients (1.2%) (Figure 1, P = 0.001). Similarly, there was higher prevalence of chronic pancreatitis (1.2%) than the control group (0.43%) (Figure 1, P < 0.001). CONCLUSION: There is a higher prevalence of acute pancreatitis in patients with CD. Patients were also found to have much higher prevalence of chronic pancreatitis in CD. This could be related to recurrent acute pancreatitis episodes in CD patients. Further studies are needed to validate these findings.

INTRODUCTION: Bariatric surgery (BRS) is an effective weight loss method that should, in theory, improve many gastrointestinal, liver, and pancreatic (GILP) diseases seen with obesity. At the same time, there is an increased morbidity related to BRS’s gastrointestinal alterations. Thus, we examined the short-term impact of BRS type on admission rates of various GILP diseases. METHODS: We queried the 2012-2014 Nationwide Readmission Database to identify obese patients who underwent vertical sleeve gastrectomy (VSG), Roux-en-Y gastric bypass (RYGB), or, as a control, hernia repair surgery (HR). Our primary aim was to compare rates of GILP diseases within 6 months post- and 6 months pre-surgery in the VSG, RYGB, and HR cohorts. In a time to event analysis we evaluated readmission rates up to 11 months post-BRS. RESULTS: We identified a total of 140,103 patients in the VSG cohort, 132,253 patients in the RYGB cohort, and 12,436 patients in the HR cohort. HR patients were slightly older with a higher percentage of Medicare insurance carriers in contrast to VSG and RYGB (Table 1). RYGB was associated with a 33-fold increased risk of intestinal obstructions compared to pre-RYGB ( P < 0.001). Other notably increased GILP diseases after RYGB from highest to lowest risk (Table 2): C. difficile infection [adjusted odds ratio (aOR): 12.52, P < 0.001], GI hemorrhage (aOR: 10.95, P < 0.001), biliary disease (aOR: 4.15, P < 0.001) and functional/motility disorders (aOR: 3.57, P < 0.001). In contrast, post- versus pre-VSG patients were most frequently admitted for acute pancreatitis (aOR: 6.26, P < 0.001), followed by C. difficile infection (aOR: 4.86, P < 0.001), biliary disease (aOR: 3.14, P < 0.001), noninfectious gastroenteritis (aOR: 3.05, P < 0.001) and functional/motility disorders (aOR: 2.74, P < 0.001). No increase in admissions was observed in the control HR cohort for any of these diseases. In our time to event analysis, the probability of being admitted was most notable for intestinal obstructions within 30 days after RYGB while functional disorders predominate afterwards (Figure 1). Similarly, patients were more frequently admitted for functional disorders following VSG. CONCLUSION: The type of BRS has a differential impact on GILP admissions after surgery. There may be a limited impact of weight loss on functional disorders that seem to dominate irrespective of BRS type. This data can help better inform patients on the choice of surgery to pursue, however more data are warranted.

INTRODUCTION: The average incidence of acute pancreatitis (AP) in patients with a history of solid organ transplant ranges from 2 to 8%. Patients with a history of bone marrow transplant are reported to have an incidence of 4%. Presentations include “chemical” pancreatitis with enzymes elevation only and clinical pancreatitis according to the revised Atlanta criteria. A few previous studies have shown that multi-organ failure and death are frequent complications of AP in transplanted patients. Most of the studies individualize their findings based on a specific organ transplanted (such as kidney or heart or liver, etc.) The aim of our study was to evaluate the outcomes of patients with acute pancreatitis with a history of any solid organ or bone marrow transplant using a national database. METHODS: We performed a retrospective cross-sectional analysis using the National Inpatient Sample (NIS) database from 2014. We included all patients with acute pancreatitis (ICD 9 Code: 577.0). Next, we divided the AP patients into two groups - one with history of a transplant and those without a history of transplant. We compared the outcomes of both groups. Both univariable and multivariable analyses were performed to assess the risk factors and outcomes of patients with acute pancreatitis in post transplant patients. RESULTS: We analyzed more than 35 million US hospitalizations in 2014 out of which 279,145 were acute pancreatitis related hospitalizations. There were 1,265 hospitalizations for acute pancreatitis in previously transplanted patients, an incidence of 4.53%. The mortality rate of AP was similar in non-transplanted patients (0.66%) than in transplanted patients (0.4%). The mean length of stay (4.62 days vs. 4.61 days) and mean total charges ($35,723 vs. $31,202) were similar in acute pancreatitis for transplant and non-transplant patients. Multivariable regression analysis showed that multiorgan dysfunction risk among AP patients was significantly higher if they had a history of transplant (OR of 2.27; P < 0.01). CONCLUSION: Our study showed that AP generally has similar outcomes in transplant and non-transplant patients even with a higher risk of multiorgan failure. More data is needed to determine if this holds true for subjects who develop AP in the immediate post transplant period.

High levels of circulating miR-16 in the serum of multiple myeloma (MM) patients are independently associated with longer survival. Although the tumor suppressor function of intracellular miR-16 in MM plasma cells (PCs) has been elucidated, its extracellular role in maintaining a nonsupportive cancer microenvironment has not been fully explored. Here, we show that miR-16 is abundantly released by MM cells through extracellular vesicles (EVs) and that differences in its intracellular expression as associated with chromosome 13 deletion (Del13) are correlated to extracellular miR-16 levels. We also demonstrate that EVs isolated from MM patients and from the conditioned media of MM-PCs carrying Del13 more strongly differentiate circulating monocytes to M2-tumor supportive macrophages (TAMs), compared with MM-PCs without this chromosomal aberration. Mechanistically, our data show that miR-16 directly targets the IKKα/β complex of the NF-κB canonical pathway, which is critical not only in supporting MM cell growth, but also in polarizing macrophages toward an M2 phenotype. By using a miR–15a-16-1–KO mouse model, we found that loss of the miR-16 cluster supports polarization to M2 macrophages. Finally, we demonstrate the therapeutic benefit of miR-16 overexpression in potentiating the anti-MM activity by a proteasome inhibitor in the presence of MM-resident bone marrow TAM.

Abstract The treatment of resected brain metastasis has shifted away from the historical use of whole-brain radiotherapy (WBRT) toward adjuvant radiosurgery (stereotactic radiosurgery [SRS]) based on a recent prospective clinical trial demonstrating less cognitive decline with the use of SRS alone and equivalent survival as compared with WBRT. Whereas all level 1 evidence to date concerns single-fraction SRS for postoperative brain metastasis, there is emerging evidence that fractionated stereotactic radiotherapy (FSRT) may improve local control at the resected tumor bed. The lack of direct comparative data for SRS vs FSRT results in a diversity in clinical practice. In this article, Greenspoon and Roberge defend the use of SRS as the standard of care for resected brain metastasis, whereas Palmer and Brown argue for FSRT.