bluuebunny/crossref_metadata_2025 huggingface dataset:
Efficacy and Safety of Fecal Microbiota Transplantation for the treatment of Clostridium difficile Infection in Patients with Liver Cirrhosis: a single center experience
Authors: Alhaffar, BS Dana , Phelps, BS Emmalee , Fischer, MD Monika
Published: January 2019

Background and Hypothesis: Fecal microbiota transplant (FMT) is an effective therapy approaching a 90% success rate for recurrent and severe CDI. However, patients with liver cirrhosis are generally excluded from FMT trials due to concerns of infectious complications. We aimed to investigate the efficacy and safety of FMT in these patients. 
Project Methods: Electronic medical records (Cerner) and an institutional FMT database (REDCap) were utilized to gather data on patient demographics, medical history, and follow-up. Inclusion criteria were the diagnosis of liver cirrhosis and FMT to treat CDI. The primary outcomes were FMT success at 8 weeks and adverse events within 12 weeks post-FMT.  
Results: Among the 267 patients in the database, 15 had liver cirrhosis. Among these, 47% (N=7) were female. The average age was 61 years (range 28-83) and they received FMT between 2014 and 2017. There were 12 (80%) patients with recurrent CDI and 3 (20%) with severe CDI. Eleven patients had decompensated cirrhosis; Child-Pough scores were A: N=4, B: N=8, and C: N=3. Five (33%) failed before 8 weeks and needed 1-3 additional FMTs for cure. Fourteen (93.3%) patients experienced adverse events. Five patients experienced unrelated SAEs (Table).  
Conclusion: Patients with liver cirrhosis failed FMT more often than non-cirrhotic historical controls. While numerous AEs and SAEs were reported, few of the AEs were possibly related to the FMT and none of the SAEs were FMT-related. Importantly, no infectious complications were observed. Larger, multicenter studies are needed to establish efficacy and safety of FMT in cirrhotics before it can be recommended for widespread use.
Inhibition of IRS-1 Alters Retinal Circadian Clock
Authors: Arif Maaz , Mathew Deepa , Bhatwadekar Ashay
Published: January 2019

Background and Hypothesis:  Life on Earth has adapted to a 24-hour cycle of light and darkness.  Circadian physiology coordinates temporal metabolism, hormone cycling, and sleep using clock genes. It is documented that dysregulation of clock gene expression is a key factor in the pathogenesis of diabetic retinopathy. Our goal was to explore the relationship between clock genes and the retina in diabetic milieu, and we hypothesized that disrupting downstream insulin signaling in a manner similar to diabetes in the retina would also affect the circadian clock.  
Experimental Design or Project Methods: In this mouse study, we used a Per2::Luc fusion protein to perform  real-time bioluminescent recording of circadian rhythms. We used SecinH3 to inhibit Insulin Receptor Signaling (IRS-1). In isolated retinas, we modulated IRS-1 to mimic the diabetic condition of impaired insulin signaling; this allowed us to directly quantify circadian rhythms in the retina. Results: Our results show that IRS-1 inhibition by SecinH3 altered the gene expression of Per2, a clock regulatory gene, over the controls. There was an increase in the period and an apparent phase shift in the presence of 100uM SecinH3.  
Conclusion and Potential Impact: Our findings can help us understand the role of insulin signaling on circadian rhythms of the retina and provide another temporal dimension to view diabetic retinopathy disease progression. Ultimately, further studies and a closer understanding of the roles of molecular clocks and insulin signaling may help to develop novel therapeutics for treating some of the harmful effects of diabetes.
Defining the function of a novel TNF receptor superfamily member
Authors: Atumonye Joseph , Turner Matthew J. , Zhou Hongming , Slominski Radomir , Dawes Avery
Published: January 2019

Background: 
Insulin Growth Factor Like 1 Receptor (IGFLR1) is a putative TNF receptor superfamily member of unknown function. Transcripts for IGFLR1 are most abundant in T cells in mice and several leukocyte subsets in humans. A major limitation to understanding IGFLR1 function is the lack of biochemical data regarding IGFLR1 expression and processing in leukocytes. 
Experimental Design: 
A panel of human leukocyte and keratinocyte cell lines was screened for IGFLR1 transcript expression by quantitative PCR. Immunoblotting was then used to detect IGFLR1 protein and characterize which isoform(s) were expressed. Chimeric IGFLR1 construct that could be used to mimic IGFLR1 activation was also generated. This chimeric protein, hNGFR-DmrB2- hIGFLR, contains two DmrB domains that allow for multimerization in the presence of AP20187.  
Results:    
IGFLR1 transcript expression varied between hematopoietic cell lines with relatively low expression in MOLT4 cells (T cell line), intermediate expression in IM9 and ARH77 cells (B cell lines) and high expression in MKB cells (T cell line). Immunoblotting in these cell lines revealed a similar protein signal expression pattern. Immunoblotting also suggested that the most abundant isoform of IGFLR1 was likely isoform c, which lacks ligand-binding and transmembrane domains. With respect to the hNGFR-DmrB2-hIGFLR1 construct, the chimeric protein was detected in CHO cells by immunoblotting and biochemical analyses confirmed that addition of AP20187 induced multimerization of this protein. These findings confirm the functionality of hNGFR-DmrB2-hIGFLR1.  
Potential Impact: 
Biochemical studies of endogenously expressed IGFLR1 in these cell lines suggest differential mRNA splicing may play an important role in the production and function of IGFLR1 isoforms. Future studies using the hNGFR-DmrB2-hIGFLR1 construct in the aforementioned human cell lines can be performed to study IGFLR1 signaling.
A Novel Small Molecule Therapy for Corneal Neovascularization
Authors: Barry Zachary , Park Bomina , Corson Timothy W.
Published: January 2019

Background and Hypothesis: Corneal neovascularization (CNV) is characterized by abnormal blood vessel growth in the avascular cornea. CNV can be caused by multiple insults such as trauma, infection, and immunological diseases. Current treatments have partial efficacy and associated side effects, revealing a need for novel treatments.  
We identified the enzyme soluble epoxide hydrolase (sEH) as a target of an antiangiogenic small molecule we developed, SH-11037. SH-11037 was antiangiogenic in mouse models for retinal and choroidal neovascularization. However, its effect on CNV has not been explored. We hypothesize that inhibition of sEH with SH-11037 will block CNV. 
Experimental Design or Project Methods: To validate sEH’s relevance in CNV, we assessed the effects of inhibition of sEH in an alkali burn CNV mouse model, treating the eyes with either eyedrops of SH-11037 or another known sEH inhibitor, t-AUCB. Neovascularization was determined by clinical assessment and immunohistochemistry. Toxicity in the retina was assessed by optical coherence tomography (OCT). Eyedrops of dexamethasone (0.1% and 0.03%) were positive controls.  
Results: Clinical assessment indicated that there was a strong trend towards a decrease in CNV in the 0.1% dexamethasone control group (p = 0.0509). Further data generation is underway, but we expect to see decreased CNV in the SH-11037 and t-AUCB experimental groups, compared to the vehicle (PBS) control group.  
Conclusion and Potential Impact: Upon completion of this study there is potential for a new therapeutic target for reducing CNV. This study provides the assessment of sEH’s involvement in CNV, which opens future areas of study.
Wound healing in diabetic Ossabaw pigs
Authors: Brown Cameron , Byrd James , Eggenberger Caleb , Nguyen Brian , Ameer Guillermo , Sturek Michael , Alloosh Mouhamad , Zhu Yunxiao , Duan Chongwen
Published: January 2019

Background and Hypothesis: Wound healing drugs are effective in mouse models of diabetes, but have not been tested in diabetic swine, whose skin more closely mimics that of humans. The primary objective was to test the wound healing efficacy of lipid nanoparticles in diabetic Ossabaw miniature swine.  
Experimental Design and Project Methods: Diabetes was induced in four Ossabaw miniature swine by ablation of the insulin-producing pancreatic beta cells and 5 months later the pigs received 8 surgically-induced skin wounds. EXCEDE was given at the time of surgery to prevent systemic infections for the first week of wound healing. Wounds were treated with drug-loaded nanoparticles in a hydrogel, an unmodified hydrogel, Promogran Prisma Matrix, or control phosphate-buffered saline (PBS). Photos were taken weekly to compare wound closure and complete skin thickness biopsies were taken for histological assessment.  
Results: Severe diabetes was verified with plasma glucose of 357±15 mg/dL (mean±SE; n=3), while 1 pig was mildly diabetic (147±18 mg/dL). All pigs exhibited glucosuria. Normal body weight was maintained to mimic human diabetics with poor glycemic control. Complete blood counts confirmed the absence of systemic infection throughout the study. After two weeks, the percent closure by treatment was 53±4% for Prisma, 48±7% for the hydrogel, 47±5% for the lipid nanoparticles, and 59±4% for PBS.  
Conclusion and Potential Impact: The data currently suggest no differences in medication efficacy, but data collection at longer durations of healing is not finished. Beneficial drug effects also may be seen on the composition (histology) of the healed skin, which has not yet been assessed.
Time to Diagnosis of Early-Onset vs. “Late-Onset” Colorectal Cancer: Is there a difference?
Authors: Chin Kayla L. , Myers Laura E. , Coffing Jessica M. , Larson Jason , Imperiale Thomas F.
Published: January 2019

BACKGROUND 
Colorectal cancer (CRC) incidence and mortality is increasing in persons ˂ 50 years old. Intervals between symptom onset and initial presentation (presentation interval [PI]) and between initial presentation and diagnosis (diagnosis interval [DI]) are not well-quantified. 
OBJECTIVE 
Compare PI and DI between early-onset CRC (EOCRC) and persons >50, and identify factors affecting these intervals.   
METHODS 
In this retrospective VA-based case-control study, we identified EOCRC cases from an ongoing study and compared them to controls (CRC patients aged ≥ 50 years). We abstracted demographics, clinical features, CRC location and stage, PI, and DI. Mann-Whitney tests compared mean and median PI and DI.  
RESULTS 
Advanced stage (III-IV) CRC was more common among the 240 EOCRC patients (mean age: 45.2, 60.8% White) than in the 234 controls (mean age: 63.8, 71.8% White): 55.4% vs 43.5%; P= 0.015. PIs and DIs, respectively, were present for 153(63.8%) and 222(92.5%) of cases and for 74(31.6%) 222(94.9%) of controls. No difference was found between median PI in EOCRC and late-onset CRC patients (42 vs 60 days, P= 0.68). The EOCRC cases had a significantly shorter median DI (41 [IQR = 16-83] vs 71 days [IQR = 32-145], P<0.0001).  
CONCLUSIONS 
In this retrospective study, younger patients had more advanced stage CRC at diagnosis than their older counterparts. However, contrary to published data, median time to diagnosis was shorter in those < 50 years. Factors associated with the DI are forthcoming. Candidate factors include race, diagnosis year, presenting symptoms, type of initial provider, CRC stage, and CRC location.
Examining Gross Anatomy Study Strategies Across Old and New Curricula
Authors: Davis, B.A. Elizabeth , Husmann, Ph.D. Polly R.
Published: January 2019

Background and Hypothesis: In the fall of 2016, Indiana University School of Medicine implemented a new integrated curriculum. We hypothesized that the study strategies utilized by students for gross anatomy changed due to this redesign.  
Project Methods: Students were given a voluntary survey about their study strategies, attitudes, and basic demographics near the end of their anatomy course. The students’ NBME and final course scores were also linked to their responses and responses were condensed into categories. Comparisons were made between students in the upper and lower thirds of the classes and between old and new curriculum cohorts.  
Results: Several differences were found between the old and new curricula: use of web-based resources increased, self-quizzing decreased, and attendance decreased at a statistically significant level (p<0.0001, p=0.042, p<0.0001). Across both curricula, students who were more confident that they had studied enough going into the tests performed more poorly than those who were less confident (p<0.0001). Consistently the students in the top third of the class demonstrated total amounts of study strategies that were lower than in the bottom third of the class, though these results did not reach statistical significance (p=0.382). 
Conclusion and Potential Impact: Student study strategies have changed between the previous and current anatomy courses in ways that may impact future student outcomes. More use of web-based resources may be of questionable quality and lead to more students feeling overwhelmed, while less self-quizzing may lead to less long-term retention of anatomy content.  Metacognitive skills remain vital across curricula.
Genoproteomic analysis of leukemic cell response to Cytarabine reveals synergistic opportunities centered on cholesterol metabolism
Authors: Farmer Alex , Chen Fangli , Wu Xue , Rogozea Adriana , Ivan Mircea , Konig Heiko
Published: January 2019

Background: Patients with acute myeloid leukemia (AML) carry a dismal prognosis due to drug resistant cancer cells that reside in O2 deprived niches of the bone marrow. Here, we sought to interrogate AML drug responses under hypoxic (1% O2) and normoxic (21% O2) conditions in order to identify novel drug targets.  
Methods: We utilized RNAseq, PCR and RPPA to interrogate chemotherapy-induced expression responses in M14 cells. We further assessed intracellular cholesterol levels (ICCLs), cell growth and apoptotic cell death per MTT and FACS analysis in AML cell lines and primary cells (PCs) in response to chemotherapy under normoxia and hypoxia.  
Results: Cytarabine blunted cholesterol biosynthesis- and induced CD36-mRNA expression under 1% and 21% O2. ICCLs were significantly higher in Cytarabine treated AML cells compared to untreated controls. Treatment with Rosuvastatin significantly inhibited growth of M14, THP1, OCI-AML3 as well as AML PCs (n=3). Further, Rosuvastatin lowered ICCLs and conferred pro-apopotic and growth inhibitory effects against M14 and THP-1 cells. Growth inhibition was enhanced when Rosuvastatin was combined with Cytarabine, yielding additive to synergistic effects. Similar effects were observed in AML PCs (n=10) where Rosuvastatin combined with Cytarabine demonstrated strong synergy.  
Conclusion: (i) Depletion of ICCLs is counterbalanced by CD36 expression in Cytarabine-treated AML cells under normoxia and hypoxia. (ii) Rosuvastatin exerts antileukemic activity in AML cell lines and PCs via downregulation of ICCLs, induction of apoptosis and inhibition of cell growth. (iii) Rosuvastatin acts synergistically with Cytarabine against AML cells. Impact: Further investigation of Rosuvastatin  in AML therapy is warranted.
Characterizing the Extent of Cell Death in Innate Immune Mediated Colitis
Authors: Hendrix Justin R. , Overstreet Anne-Marie , Boger-May Antonia , Boone David
Published: January 2019

Background and Hypothesis:  
Intestinal epithelial cell (IEC) turnover occurs every four-to-five days. In inflammatory bowel disease (IBD), IECs undergo increased cell death due to inflammation of intestinal villi and colonic crypts. This cell death leads to increased permeability of the intestinal barrier. This study examined the pathogenesis of IBD, focusing on innate immunity using mice with spontaneous innate immune colitis. The objective was to observe if there is a significant difference in expression of apoptosis in colitic mice vs. control mice. 
Experimental Design: 
Mice expressing the NF-kB inhibitor TNFAIP3 in the villi of IECs were interbred with RAG1-/- mice. TNFAIP3 x RAG1-/- (TRAG) mice developed 100% penetrant colitis by 6 weeks of age that was not observed in TNFAIP3 or RAG1-/- littermates. The presence of activated caspase-3 in distal colons was detected using immunofluorescence and quantified using ImageJ to compare differences between 4- and 8-week-old RAG vs.TRAG mice.  
Results: 
Increased numbers of caspase-3+ cells were found in TRAG mice compared to RAG mice. After treatment with antibiotics, similar levels of capase-3 were detected in both groups.  
Conclusion and Potential Impact: 
This investigation suggests that cell death in TRAG mice were increased due to deficient innate immunity in IECs. Thus, bacteria play a direct role by killing IECs or an indirect role by causing inflammation. Understanding how innate immune activation drives cell death in IECs, may lead to a better understanding of the complex regulation of IBD, and improved therapeutic agents targeting novel cell types in the remission of chronic IBD.
Leukocyte Localization in a Model of Innate Immune-Driven Colitis
Authors: Jones Jordan R. , Overstreet Anne-Marie C. , Boger-May Antonia M. , Boone David L.
Published: January 2019

Background and Hypothesis: 
Inflammatory bowel disease (IBD) is a disabling, chronic gut disorder involving immune dysregulation. Our lab has generated a murine IBD model in which the innate immune system drives inflammation. Innate lymphoid cells (ILCs), an innate immune cell subset that was recently discovered, exhibit many T-helper cell characteristics. ILCs, though few, produce cytokines, thereby significantly impacting tissue through local action in mucosal sites. They express the cell surface markers, CD90, which is unique to ILCs, and CD45, which all leukocyte types express. Colitis prevention in our model via ILC depletion indicates a role for ILCs in IBD. Therefore, we aimed to identify the ILCs’ localization in our murine model. We hypothesized that the ILCs will localize to inflamed areas of the intestinal lamina propria and into the intraepithelial spaces. 
Experimental Design or Project Methods: 
Mice expressing TNFAIP3, an inhibitor of NF-kB, were mated with adaptive immunity-lacking mice (RAG1-/-). RAG1-/- x Villin-TNFAIP3 (TRAG) mice had colitis that was 100% penetrant by age 6 weeks. Distal colons excised at age 4 weeks and 8 weeks were used for identifying CD45+ and CD90+ cells in both RAG and TRAG mice intestines via immunofluorescence. 
Results: 
We observed differences in the distributions of CD90+ and CD45+ cells within TRAG and RAG mice intestines. 
Conclusion and Potential Impact: 
Differences exist in intestinal leukocyte distributions within our models. Altered ILC distribution might reflect an inflammatory state or contribute to IBD pathology. This work may further elucidate ILCs’ role in IBD and as IBD treatment targets.
Birth Spacing and Family Planning: Implementation of enhanced education and training for Community Health Coaches
Authors: Jostes, BS BA Alexandra , Griffin, MS Wilma , Dechant, BS Paige , Otero, BA Carolina , Sobiech, PhD Kathleen , Chico, BA Denise V. , Litzelman, MD Debra
Published: January 2019

Background: Indiana is ranked 43/50 for infant mortality in America. WeCare employs lay Community Health Coaches (CHCs) to promote positive behavioral changes in pregnant, postpartum and women of child-bearing age living in low-income, high-risk communities in order to reduce the risk of infant mortality. Infant mortality can be reduced in communities where birth spacing and family planning education are available.  
Project Methods: The goal was to address the knowledge gaps in patient handouts and CHC training regarding birth spacing and family planning. Through extensive literature searches, case conferences with CHCs, and review of current training materials, five gaps in training were identified: (1) comprehensive knowledge of rapid repeat pregnancies (2) resources regarding contraceptive methods (3) contraceptive counseling in the antenatal and postpartum periods (4) joint decision-making models and (5) father involvement in family planning. 
Results: With comprehensive literature reviews and collaboration with fellow WeCare members, the gaps in training were appropriately filled. The WeCare training manual for CHCs is updated with information regarding birth spacing and family planning, as well as with counseling techniques for contraceptive method decision-making. A gap in existing literature regarding father involvement in family planning was identified.  
Conclusion and Potential Impact: By enhancing CHC education on birth spacing, family planning, and counseling techniques, we may begin to close the knowledge gap for women in low-income, high-risk populations. This has the potential to reduce the rate of rapid repeat pregnancies and unintended pregnancies. We have also opened a new avenue of research about father involvement in family planning in the US.
Store operated calcium entry in diabetic macrophages is reduced in fasting conditions
Authors: Lee Regina , Beli Eleni , Lee Chih-Chun , Kono Tatsuyoshi , Evans-Molina Carmella
Published: January 2019

Background and Hypothesis: 
In diabetic mice, intermittent fasting (IF) prevents diabetic complications by temporarily reducing inflammation during the fasting period. As calcium homeostasis is tightly connected to the inflammatory response, we hypothesize that IF regulates macrophage response by altering store-operated calcium entry (SOCE). SOCE, mediated by the STIM and ORAI families, is the primary form of calcium entry into the cell. 
Experimental Design or Project Methods: 
We assessed SOCE levels in control and diabetic (INS2Akita) mouse primary macrophages stimulated with a metabolic stimulus (MET: insulin, high glucose, palmitate) to mimic feeding and a starvation stimulus (STARVE: low glucose, low FBS, oleate) to mimic fasting. SOCE levels were measured by a Flexstation using Calcium-6 dye. We also assessed gene expression of SOCE components by RT-PCR and STIM1 and ORAI1 proteins by western blot.  
Results: 
A decrease in SOCE was observed with MET stimuli and an increase with STARVE stimuli in control macrophages. Interestingly, gene expression and protein levels of all major SOCE components, including STIM1 and ORAI1, were increased in the MET and decreased with STARVE. While diabetic macrophages had similar SOCE function than control under basal and MET conditions, they showed significantly downregulated SOCE under starvation conditions. 
Conclusion and Potential Impact: 
These data show that diabetic macrophages have altered SOCE function in response to fasting. This could have potential impact on how diabetic individuals respond to nutritional interventions such as IF that are recently proposed for prevention of diabetic complications.
Type 2 Diabetes Mouse Model: Insights into the Contribution of Metabolic Defects to Neurocognitive Decline
Authors: Loncharich Alexa , Reilly Austin , Yan Shijun , Ren Hongxia
Published: January 2019

Background and Hypothesis: Metabolic diseases, including type 2 diabetes (T2D), have become increasingly prevalent and their associated medical costs have skyrocketed. Furthermore, recent epidemiological evidence suggests links between metabolic defects and neurodegenerative diseases, such as Alzheimer’s Disease (AD). The increasing coincidence of AD and T2D, and unmet treatment needs, necessitates research investigating potential shared mechanisms. To study glucose and lipid metabolism defects and neurocognitive deficits, we have generated non-obese insulin resistant mouse models, named GLUT4-mediated Insulin Receptor KnockOut (GIRKO). Insulin-responsive glucose transporter, Glut4, is expressed in muscle, fat, and a subset of neurons in the brain. Our previous publications show that GIRKO mice are highly insulin resistant and insulin sensitive GLUT4 neurons are critical mediators for glucose metabolism. We hypothesize that central insulin resistance in GIRKO mice instigates neurocognitive defects. 
Experimental Design: We will measure the neurocognitive function of 3- to 4-month old GIRKO mice using Morris water maze (MWM) test.  
Results: GIRKO mice exhibited increased escape latency. Additionally, they spent less time in the target quadrant in the probe trial, in which the platform is removed. GIRKO performed equally compared to control mice in raised platform tests, which demonstrates that motor competencies do not confound our findings. 
Conclusion and Potential Impact: GIRKO mice have learning and memory deficits, which illustrates a possible link between neurocognition and metabolism.  Our results support the notion that insulin resistance precedes cognitive decline and necessitates early intervention therapy to treat insulin resistance and protect cognitive function.
Cardiovascular Effects of Sodium Glucose Cotransporter-2 (SGLT-2) Inhibition in the Setting of Ischemia/Reperfusion Injury
Authors: Luebbe Sam , Baker Hana E. , Mather Kieren J. , Goodwill Adam G. , Simon Blake R. , Earl Conner C. , Tune Johnathan D.
Published: January 2019

Background and Hypothesis: Recent evidence indicates that sodium glucose cotransporter-2 inhibitors (SGLT2i) significantly reduce the incidence of major adverse cardiovascular events in high risk patients. However, the specific effects of SGLT2i on the cardiovascular system remain poorly defined. This study was designed to test the hypothesis that SGLT2i improves cardiac function and mitigates myocardial infarct size following regional myocardial ischemia and reperfusion injury. 
Experimental Design: Lean domestic swine received placebo (n=6) or canagliflozin (n=6; 300 mg PO) 24 hours prior to and the morning of an experiment. Hemodynamics, left ventricular pressure and volume were measured in open chest, swine at baseline, during a 60 min coronary occlusion, and during a 2-hour reperfusion period. The degree of myocardial infarction was assessed by staining with 1% tetrazolium. 
Results: At the onset of ischemia, SGLT2i produced a significant parallel increase in both left ventricular end diastolic (85 ± 9 mL to 129 ± 10 mL; P < 0.05) and end systolic volumes (29 ± 8 mL to 78 ± 9 mL; P < 0.01). This increase in ventricular filling was associated with significant increases in stroke volume (P < 0.05) and stroke work (P < 0.05) relative to untreated controls swine during ischemia.  SGLT2i decreased infarct size from 9.4 [Symbol] 2.1% in control swine to 3.1 [Symbol] 0.98% in SGLT2i treated swine. 
Conclusion: SGLT2 inhibitors significantly improve cardiac contractile function and mitigate myocardial infarct size following regional myocardial ischemia and reperfusion injury in domestic swine.
Fidelity of Peer Supported Self-Management of Chronic Pain (Evaluation of a Peer Coach-Led Intervention to Improve Pain Symptoms—ECLIPSE)
Authors: Mannon, B.S. Joyce S. , Matthias, Ph.D. Marianne S.
Published: January 2019

Background: ECLIPSE (Evaluation of a Peer Coach-Led Intervention to Improve Pain Symptoms) is a randomized controlled trial testing peer-supported chronic pain self-management. Veterans are paired with a peer coach (also with chronic pain) for 6 months. Peer coaches (PCs) and veterans meet or talk by phone 2x/month about pain self-management strategies, and veterans receive motivation and encouragement from their PC. To determine if the intervention was delivered as intended, fidelity was assessed at the end of the intervention period. Fidelity assessment is vital to help understand reasons for an intervention’s success or failure.  
Methods: Intervention veterans were asked about the intervention’s delivery during their 6-month assessment, after intervention completion. Presence or absence of four “essential elements” of the intervention were evaluated, as well as meeting frequency.   
Results: Scoring of veteran assessments revealed 74% of PC’s discussed self-management strategies and 69% of veterans felt motivated by their PC. Only 52% discussed how to adjust strategies and 34% discussed goal-setting. PC-veteran meeting frequency varied: 16% met weekly, 21% met twice a month, 16% met once a month, and 46% met less than once a month. 47% of PC’s had greater than 75% fidelity (i.e., the presence of at least 3 of 4 elements described above).  
Conclusion and Potential Impact: About half of PC’s delivered the intervention with at least 75% fidelity. Fidelity was greater for discussing self-management strategies and motivating veterans. Results suggest that peer-supported self-management can be delivered with fidelity but PCs may need additional training to do so consistently.
MELodica Orchestra for DYspnea (MELODY): A Randomized Safety, Feasibility, and Efficacy Pilot
Authors: McGrath Mackenzie , Burns Debra S. , Crow Shannon , Lillie Aimee , Myers Laura J. , Myers Jennifer , Perkins Anthony J. , Rattray Nicholas , Smith Joseph , Wasmuth Sally , Bravata Dawn M.
Published: January 2019

Background 
Chronic obstructive pulmonary disease (COPD) is highly prevalent among Veterans. Patients with COPD commonly experience dyspnea, which can be debilitating and may limit daily activities leading to a reduced quality of life. Pulmonary rehabilitation often includes teaching pursed lip breathing as a method to reduce dyspnea. However, patients with COPD, including Veterans, have limited access to pulmonary rehabilitation due to transportation constraints and lack of referrals by physicians. 
Methods 
MELodica Orchestra for DYspnea (MELODY) is a randomized controlled clinical trial designed to assess the safety, feasibility, and efficacy of a music-based approach to teach pursed lip breathing to Veterans with COPD experiencing dyspnea. Patients will be randomized in a 1:1:1 ratio to the intervention group, education only control group, and usual care control group using block randomization. Patients in the intervention group will meet twice weekly over twelve weeks for instruction on how to play the melodica and to participate in group music-making. The program also includes education about COPD, pursed lip breathing, tobacco cessation, and other relevant topics. Each participant will receive quantitative assessments (e.g., exercise endurance and dyspnea scales) and participate in qualitative interviews.  
Anticipated Results 
We expect the intervention to be safe and feasible. We hypothesize that patients in the intervention group will achieve the greatest reduction in dyspnea compared with patients in either control group. 
Potential Impact 
If pilot data demonstrates efficacy, then a multiple-site randomized control trial will be conducted with intent to introduce the program into routine clinical practice.
Association of AHI and Other Patient Factors with Calvarial Thickness
Authors: Nag, BS Amit , Rabbani, MD Cyrus , Saltagi, MD Mohamad Z. , Schueth, BS Elizabeth , Nelson, MD, PhD Rick F.
Published: January 2019

Background and Hypothesis: Temporal spontaneous cerebrospinal fluid (sCSF) leaks occur when spinal fluid leaks through defects in the skull base bone. Patients with sCSF leaks have approximately 22% thinner skulls but no change in extracranial bone thickness, suggesting an intracranial process causes skull thinning and the development of sCSF leaks.  Approximately 83% of sCSF leak patients have obstructive sleep apnea (OSA) as measured by the apnea-hyponea index (AHI) and OSA is associated with spikes in intracranial pressure. We hypothesize that AHI is associated with isolated skull thinning in the general population. 
Experimental Design:  High resolution head CT images from patients with diagnostic sleep studies at IU health from 2010 to 2017 were analyzed (IRB approved) using 3D slicer to measure skull thickness of the squamous temporal bone. Age, body mass index (BMI), race and diabetes recorded. Mixed model analysis was used to determine the effect of a number of factors on skull thickness. 
Results: 344 CT scans were analyzed. Increased AHI was significantly associated with thinning of the calvarium [2.68 mm - 0.003x, (x = AHI point)  P<0.02], while thickening of the calvarium was associated with age [CI = 0.005 to 0.011 per year, P<0.001] and BMI [CI = 0.003 to 0.015 per mg/kg2, P<0.003]. Female gender (P=0.016) and diabetes (P=0.005) were linked to thickening of the calvarium. Hypertension had no effect on calvarial and zygoma thickness (P=0.244 and 0.575, respectively). The extracranial zygoma thickness was not associated with AHI (P=0.54) or BMI (P=0.811) but the zygoma thinned significantly with age [CI = -0.01 to - 0.002, P<0.002] and female gender (P<0.001). 
Conclusion and Potential Impact:  OSA is associated with skull thinning and may play a pathologic role in the development of sCSF leaks over time.
Role of Endoscopic Retrograde CholangioPancreatography (ERCP) and Intraductal Secretin Test (IDST) in the Diagnosis of Chronic Pancreatitis (CP)
Authors: Osuji Vitalis C. , McNulty, RN, BSN, CCRC Gail , Fogel, MD, MSc, FRCP(C) Evan
Published: January 2019

Background:  
CP may be difficult to diagnose in the early stages when imaging may be normal. An IDST performed at ERCP may further evaluate for CP, with determination of pure pancreatic juice (PPJ) volume and bicarbonate concentration (BC). The optimal collection time for IDST is unknown. We report our experience with the IDST in 447 patients with suspected CP.           
Experimental Design:  
IDSTs performed from 2006-2018 were reviewed, with fluid collected at 5-min intervals for 20-60 minutes. Parameters evaluated were PPJ volume, Secretory Flow Rate (SFR), time of peak SFR, maximum BC and time to maximum BC.         
Results:  
Maximum BC was reached by 10-min in 59 patients (13.2%); 15-min: 207 patients (46.3%); 20 min: 340 patients (76.1%); 25-min: 384 patients (85.9%); 30-min: 421 patients (94.1%). Peak SFR was reached by 10-min in 92 patients (20.6%); 15-min: 177 patients (39.6%); 20-min: 240 patients (53.7%); 25-min: 284 patients (63.5%); 30-min: 323 patients (72.3%). Final diagnosis (normal vs. CP) for both SFR and BC was determined by 20-min (i.e. in CP pts, either the SFR or BC was low (SFR <3ml/min, BC <105mEq/L) and remained low throughout collection, or normal (>3ml/min and >105mEq/L) within the first 20-min. Further collection did not change the diagnosis. 
Conclusion:  
At IDST, a 20-minute collection period is necessary to categorize patients into normal or suspected CP groups. A study in control patients (no suspicion of CP) to validate these data is currently underway.
Fecal Bile Acids and Fecal Short Chain Fatty Acids in Patients with Irritable Bowel Syndrome and Control Volunteers
Authors: Patel Chirag , Lockett Carolyn , Xu Huiping , Shin Andrea
Published: January 2019

Background and Aims: Fecal bile acids (BAs), short chain fatty acids (SCFAs), and gut microbiome may be implicated in irritable bowel syndrome (IBS) pathophysiology. Our aim was to compare fecal organic acids between IBS with constipation (IBS-C), IBS with diarrhea (IBS-D), and controls.  
Methods: Stool samples were collected from 17 controls, 5 IBS-C, and 5 IBS-D volunteers during a 4-day high fat diet. Aliquots were stored for future analysis of the fecal microbiota. Fecal SCFA and BA analyses were conducted at the Metabolite Profiling Facility at Purdue University and Laboratory Medicine and Pathology at Mayo Clinic. We compared SCFA and BA levels among groups using the Wilcoxon rank sum test. Gamma and linear regression were used to compare SCFAs and BAs adjusting for age and body mass index (BMI). 
Results: Fecal acetate levels (mean+SD, µg/mg) were higher in IBS-C (11.3±7) than in controls (6.1±3.3) or IBS-D (7.7±2), although not statistically significant (p=0.19). Total fecal BAs (median [IQR], %) were higher in IBS-D (675 [484-778]) than in controls (342 [130-640]) or IBS-C (321.5 (34.5-718); however, differences were not significant. No significant differences were observed in BAs or SCFAs between groups in multivariate analyses. 
Conclusion: We are unable to show significant differences in organic acid levels in IBS and controls. Lack of association may be due to small sample size. Future investigation of larger patient numbers with incorporation of transit and microbiome analyses may shed further light on the role of organic acids in IBS to identify new biomarkers and treatment targets.
Surveying ADR knowledge and practices among US gastroenterologists
Authors: Peng Michael , Rex, MD, MACG Douglas
Published: January 2019

Background:  
The adenoma detection rate (ADR) is of primary importance to the quality of screening colonoscopy. An online survey was conducted to assess knowledge and practices on ADR. 
Methods: 
Paid questionnaire distributed by email. Eligible respondents were board certified gastroenterologists who perform >80 colonoscopies per month with 3 to 35 years after fellowship. 
Results: 
39% were unaware that ADR applies only to screening colonoscopies and 76% incorrectly answered that ADR includes sessile serrated polyps/adenomas.  51% of respondents incorrectly believe the threshold is set at 25% because 25% is a national ADR average. Many also believe the threshold depends on the patient population (current evidence suggests adjusting ADR for factors other than age and sex is unnecessary). 75% ranked ADR as highly important. 80% reported tracking ADR. A busy practice was the most common reason for not tracking ADR. Caps, chromoendoscopy, and good bowel preparation were viewed as valuable for improving ADR (this is true except for caps). HD colonoscopes and education were considered less valuable (although evidence suggests HD and education are associated with improved ADR). 57% reported not sharing ADR information with their patients, and 59% reported no patients in the past 6 months asking for their ADR.
Conclusion: 
The importance of ADR as a validated quality measure is well understood, but there are misconceptions among gastroenterologists regarding the definition and measurement of ADR and which methods are proven to increase ADR.  Patients are having very little impact on ADR measurement.
Outcome of Pediatric Emergency Point-of-Care Ultrasound (POCUS) for Management of Skin and Soft Tissue Infection Prior to Ultrasound Program Implementation
Authors: Phillips, BS Whitney , Nti, MD, MSc Benjamin
Published: January 2019

Background and Hypothesis: Point-of-care ultrasound (POCUS) is underutilized for evaluation of skin and soft tissue infections (SSTI) in the pediatric emergency department (ED). This study seeks to determine the utilization of POCUS compared to formal radiology ultrasound for SSTI in the pediatric ED prior to an ultrasound program implementation. We hypothesize that POCUS utilization will be low but can lead to a decreased length of stay (LOS) and cost for patients with SSTI. 
Experimental Design or Project Methods: This is a retrospective EMR chart review covering pre-implementation (July 2016-June 2017) and post-implementation (July 2018-June 2019) of a POCUS program curriculum. Patients (<18 years old) were included based on screening for diagnoses via the international classification of diseases 9th and 10th revision codes for abscesses and cellulitis. We excluded patients who required admission and subspecialty consult or had other non-SSTI evaluation.  
Results: Pre-Implementation period included 160 patients who met inclusion and exclusion criteria. Of these, 16 (10%) received POCUS evaluation and 8 (5%) received a radiology image evaluation. The majority of patients had cellulitis (80%) when compared to abscess (20%). The average LOS for POCUS ultrasound was 173 minutes compared to 304 minutes for radiology evaluation. The total cost for visit was $3,503 for patients evaluated by POCUS compared to $8,875.56 for patients who received radiology imaging. 
Conclusion and Potential Impact: Taken together, the pre-implementation assessment of POCUS utilization in the pediatric emergency department was low but associated with decreased LOS and lower total ED cost when applied to SSTI management.
Early Pain, Narcotic Use, and Functional Recovery in Aseptic Revision Total Knee Arthroplasty Performed with Morphine Spinal Analgesia versus Fentanyl Spinal Analgesia with Adductor Canal Block
Authors: Rice, BA Justin , Mohiuddin, BS Amer , Nielson Trent , Ziemba-Davis, BA Mary , Meneghini, MD R. Michael
Published: January 2019

Background and Hypothesis: There has been a trend away from intrathecal morphine for perioperative pain control during and after total knee arthroplasty (TKA) and it has been replaced by shorter-acting non-morphine spinals combined with adductor canal block (ACB) regional analgesia. The purpose of this study is to compare pain control and side-effects between morphine intrathecal alone and fentanyl spinal with ACB in revision TKA. 
Project Methods: Prospectively collected data on 167 consecutive aseptic revision TKAs performed by a single surgeon between 2010 and 2017 were retrospectively reviewed.  Inpatient pain, narcotic use, functional milestones, complications, and four-month patient reported outcomes were compiled for the two cohorts (110 fentanyl/ACB and 57 morphine cases). 
Results: Average age (p=0.66) and BMI (p=0.542) were equivalent in the two cohorts (p=0.542). Fentanyl/ACB patients gained more range-of-motion (ROM) by 4-month follow-up (p=0.051) than morphine patients.  However, fentanyl/ACB patients had higher average pain scores (p=0.006), consumed opioids earlier (p<0.001), and consumed more opioids (p<0.001) on postoperative day one. Morphine analgesia was associated with more nausea/vomiting (p=0.001) and pruritus (p=0.00001). 
Conclusion and Potential Impact: Morphine intrathecal patients reported less inpatient pain and consumed less opioid, which most likely reflects morphine’s longer half-life. Improved 4-month ROM in the fentanyl/ACB group may reflect the quadriceps-sparing nature of ACBs. It is also possible that the operative field in revision TKA extends beyond the sensory protection of ACB.  Further research is required to elucidate the relative impact of ACBs on primary vs. revision procedures.
Comparison of two techniques using EUS guided liver biopsies via 19g core biopsy needle to obtain optimal core specimen in benign disease
Authors: Rumancik Brad , Kota Sharwani , Irvin Judy , Zelt Christina , Mirro Michael , Sharma Neil
Published: January 2019

Background and Hypothesis: 
Endoscopic ultrasound (EUS) guided fine-needle biopsy (FNB) to obtain core liver specimen is shown to be effective and safe. However, prospective data is limited regarding EUS-FNB in non-malignant liver disease. This study evaluates two EUS-FNB techniques with the hypothesis that the modified wet suction (MWS) technique will produce greater pathological yield than the slow pull (SP) technique in patients with non-malignant liver disease. 
Experimental Design or Project Methods: 
In this prospective, randomized controlled trial we are evaluating efficacy and safety of EUS-FNB techniques (MWS versus SP) in patients with initial indication for an upper endoscopy plus need for a liver biopsy to assess non-malignant disease. The primary outcome is pathological yield defined as number of complete portal tracts (CPTs), specimen length, and fragmentation. Secondary outcomes include pathological yield between two specimen processing techniques, pathological yield between left versus right liver lobe biopsy, time for biopsy technique, and complications. 
Results: 
For this interim analysis, 8 patients (5 received MWS and 3 received SP) out of a projected total of 360 patients are enrolled. Independent t-test analysis reveals no statistical difference between CPTs (P=0.56), specimen length (P=0.12), and fragmentation (P=0.16). No differences are found between any secondary outcomes, and there have been no biopsy-related complications.    
Conclusion and Potential Impact: 
This underpowered interim analysis reveals no statistical difference in primary or secondary outcomes between MWS versus SP technique. The current results for both groups are consistent with specimen adequacy criteria determined by American Association for the Study of Liver Disease.
Increasing Adolescents’ Access to the HIV Continuum of Care: Development of a Screening Tool for Medical Legal Partnerships
Authors: Scalzo Anna C. , Gilbert, JD, MPH Amy L.
Published: January 2019

Background: Research has shown that at-risk youth are not being reached by HIV testing efforts and are encountering barriers at other points along the HIV Continuum of Care (CoC). Legal remedies often exist for youth and their families in addressing barriers to the HIV CoC. The purpose of this study was to develop a targeted screening tool for identifying unmet health-harming legal needs that create barriers to the HIV CoC at the level of individual youth, to be used in clinics with Medical Legal Partnerships (MLPs) designed to address such barriers through legal intervention.  
Project Methods: A literature search was completed to investigate if validated screening questions already existed for the 10 areas of adolescent health-harming legal needs previously identified from qualitative interviews with at-risk youth and care providers. A focus group of legal professionals was conducted to better understand the range of legal solutions that exist and identify critical concepts and language for screening questions. 
Results: The study team developed a brief survey that can be used in clinic to screen individual adolescents for potential, actionable legal needs. Some questions were adapted from existing resources, while others were newly synthesized.  
Conclusion and Potential Impact: The screening tool will be piloted with a representative sample of at-risk youth and eventually implemented in adolescent-focused FQHC sites with active MLPs. This tool will be used to identify actionable legal needs and prompt referrals to legal professionals who can help adolescents resolve health-harming legal needs that may prevent access to the HIV CoC.
Predictors of Patient Function, Pain, and Satisfaction after Reimplantation for Infected Hip and Knee Arthroplasty
Authors: Sikoski Christian , Ziemba-Davis, BA Mary , Meneghini, MD R. Michael
Published: January 2019

Background/Hypothesis: Prevalence of periprosthetic joint infection (PJI) is expected to rise as hip and knee arthroplasty procedures increase. This study purpose was to evaluate factors affecting patient-reported outcomes after resection and reimplantation procedures.  
Project Methods: 38 hips and 35 knees consecutively treated by a single surgeon were retrospectively reviewed. Prospectively collected preoperative and minimum one and two-year postoperative Knee Injury and Osteoarthritis Outcome Score/KOOS Jr., Hip Disability and Osteoarthritis Outcome Score/HOOS Jr., UCLA Activity Level, and satisfaction were compiled. Fifteen demographic variables and covariates of outcomes (sex, age, etc.) were accounted for in analysis.   
Results: 47% of hip and 71% of knee patients were chronically infected poor hosts (McPherson stage III-B/C). In hips, worse McPherson stage was associated with lower activity levels at latest follow-up (p=0.007). Activity was higher in hip patients with constrained liners compared to dual mobility implants at one (p=0.009) and two-year (p=0.001) follow-up. The same result was observed in knees with varus-valgus constrained liners vs. hinged implants (p=0.005, p=0.029). However, varus-valgus constrained articulations were associated with more stair pain at one (p=0.003) and two (p=0.012) years. 83% of hip and knee patients were satisfied or very satisfied with their outcome at latest follow-up.  
Conclusion/Potential Impact: Positive outcomes observed following reimplantation procedures will help establish patient expectations.  It appears the increased joint stability imparted by hinged TKA and constrained liners in THA may offer advantage in stair pain and clinical function, respectively, in reimplantation arthroplasty after PJI.