bluuebunny/crossref_metadata_2025 huggingface dataset:
Species interactions constrain adaptation and preserve ecological stability in an experimental microbial community
Authors: Barber Jake N , Nicholson Luke C , Woods Laura C , Judd Louise M , Sezmis Aysha L , Hawkey Jane , Holt Kathryn E , McDonald Michael J
Published: January 2022

Species loss within a microbial community can increase resource availability and spur adaptive evolution. Environmental shifts that cause species loss or fluctuations in community composition are expected to become more common, so it is important to understand the evolutionary forces that shape the stability and function of the emergent community. Here we study experimental cultures of a simple, ecologically stable community of Saccharomyces cerevisiae and Lactobacillus plantarum, in order to understand how the presence or absence of a species impacts coexistence over evolutionary timescales. We found that evolution in coculture led to drastically altered evolutionary outcomes for L. plantarum, but not S. cerevisiae. Both monoculture- and co-culture-evolved L. plantarum evolved dozens of mutations over 925 generations of evolution, but only L. plantarum that had evolved in isolation from S. cerevisiae lost the capacity to coexist with S. cerevisiae. We find that the evolutionary loss of ecological stability corresponds with fitness differences between monoculture-evolved L. plantarum and S. cerevisiae and genetic changes that repeatedly evolve across the replicate populations of L. plantarum. This work shows how coevolution within a community can prevent destabilising evolution in individual species, thereby preserving ecological diversity and stability, despite rapid adaptation.
Ferroelectrically augmented contact electrification enables efficient acoustic energy transfer through liquid and solid media
Authors: Kim Hyun Soo , Hur Sunghoon , Lee Dong-Gyu , Shin Joonchul , Qiao Huimin , Mun Seunguk , Lee Hoontaek , Moon Wonkyu , Kim Yunseok , Baik Jeong Min , Kang Chong-Yun , Jung Jong Hoon , Song Hyun-Cheol
Published: January 2022

Acoustic energy transfer using ferroelectrically augmented triboelectric receivers can efficiently deliver energy to implantable medical devices, marine cable operation sensors, and electronic devices with electromagnetic interference shielding cases.
Structural characterization and in vitro hypoglycaemic activity of glucomannan from Anemarrhena asphodeloides Bunge
Authors: Chen Juncheng , Wan Liting , Zheng Qingsong , Lan Meijuan , Zhang Xia , Li Yuting , Li Bing , Li Lin
Published: January 2022

A new polysaccharide (AABP-2B) was obtained from Anemarrhena asphodeloides Bunge after purification by gradient alcohol precipitation and DEAE-52 cellulose column chromatography.
Enantioselective difunctionalization of alkenes by a palladium-catalyzed Heck/borylation sequence
Authors: Wu Yuanqi , Wu Lizuo , Zhang Zhan-Ming , Xu Bing , Liu Yu , Zhang Junliang
Published: January 2022

A palladium catalyzed enantioselective Heck/borylation reaction of alkene-tethered aryl iodides was realized, delivering a variety of 2,3-dihydrobenzofuranyl boronic esters in high yield with excellent enantioselectivity.
Recognizing Uncertainty in Forest Planning: A Decomposition Model for Large Landscapes
Authors: De Pellegrin Llorente Irene , Hoganson Howard M , Windmuller-Campione Marcella A
Published: January 2022

Multiple ecological, economic, social, and political facets influence forest-planning decisions. Decision models have been widely used in forest management planning, but most are deterministic models. However, long-term forest planning problems are surrounded by potential uncertainties. To begin to account for uncertainty surrounding growth and yield under climate change conditions, a stochastic forest planning model was developed and tested. The intent of the model is to help identify potential current forest management actions that will perform well over a range of plausible climate change scenarios (futures). The stages of the model address how uncertainty about the future might unfold, with model solutions providing immediate management actions plus detailed contingency (recourse) plans for each future. The use of specialized decomposition methods of operations research has allowed for testing the model in a detailed and large application. Results from the case study showed that planning for an average deterministic case produces a misleading solution, underestimating the potential impact of climate change. On the other hand, only planning for a worst-case scenario ignores the potential value of management opportunities under other likely futures in which harvesting benefits could be greater. Overall, results advance our understanding of recognizing forest-wide uncertainty in forest management planning models.

Study Implications

Stand-level decisions often have forest-wide implications. Forest planning helps coordinate management of stands to address ecological, economic, and social aspects. Decision models are often used, but most assume all the information is known. However, long-term forest planning is surrounded by potential uncertainties, such as climate change. We developed a model to identify current forest management actions that will perform well over a range of plausible climate change scenarios instead of just one. The novelty lies in how we solve the problem. Breaking it into smaller subproblems allows us to include more stand-level details while still tackling a large problem.
CELLULAR AND MOLECULAR IMPACT OF THE MELANOCORTIN RECEPTOR AGONIST PL8177 IN DEXTRAN SODIUM SULFATE (DSS)-INDUCED COLITIS IN RATS
Authors: Dhingra Priyanka , Obr Alison , Spana Carl , Dodd John , Kayne Paul
Published: January 2022

INTRODUCTION

The melanocortin 1 receptor (MC1r)–specific agonist PL8177 and its main metabolite PL8435 have demonstrated MC1r binding affinity and functional activity that mirrors that of α-melanocyte stimulating hormone (a-MSH). a-MSH has been demonstrated to be effective in reducing inflammation in numerous experimental models. This study investigates the effects of PL8177 on inflammation, cell population composition, and gene and protein expression in colons from a DSS–induced rat model of colitis. The objective is to determine the effectiveness of PL8177 in this model and to characterize its underlying mechanism of action.

METHODS

Male Wistar rats received 5% DSS in drinking water for 3 days to induce colitis. Rats in the sham group received drinking water only (each group n=6). The other groups received vehicle control (placebo)–filled capsules; PL8177-filled capsules at 20, 50, and 100 μg/animal (by oral gavage); or oral mesalazine (positive control). At termination on day 8, 24 hours after the last dosing, colon tissues were harvested, dissected and snap frozen with liquid nitrogen. Colon samples were analyzed for cytokine levels, single nuclei RNA-seq, and data-independent acquisition tandem mass spectrometry (LC/MS DIA). Colitis was assessed by a disease activity index (diarrhea and rectal bleeding), colon length shortening, colon weight gain, and histopathological assessment. The total colitis index, was used to assess inflammatory damage.

RESULTS

Colitis was induced in rats treated with DSS. Oral PL8177 50 μg/animal treatment showed a significant improvement in colon weight (53% reduction), stool consistency, and fecal occult blood score compared to vehicle. There was a significant (P<0.05) improvement in the total colitis index for the PL8177 100-μg group vs vehicle control group. All PL8177-cohorts showed greater improvement in the total colitis index compared to the mesalazine-treated cohort. PL8177 50 μg/animal showed a significant improvement in colon weight (53% reduction), while mesalazine treatment was associated with significant reduction in colon length, but only moderate improvement (35%) in colon weight. Changes in the cellular population compositions, gene expression changes and protein level data will be presented and discussed at the conference.

CONCLUSION

Oral PL8177 treatment of inflamed colon showed significant improvement in markers of colitis in the rat model compared to the placebo and mesalazine control groups supporting the aim of treating inflammatory bowel disease in humans. Genomic and proteomic data will be interpreted in the context of disease change to identify alterations in immune and cellular states of the experimental colons.
MTADV 5-MER PEPTIDE SUPPRESSES IBD PATHOLOGY AND UNVEILS A NEW POTENTIAL TARGET-SERUM AMYLOID A
Authors: Naor David , Cowman Mary , Kim Jin , Hemed-Shaked Maayan
Published: January 2022

We reported in the previous Crohn’s and Colitis Congress and published in Refs 1 and 2 ,that a segment of 5 aa of a CD44 variant -Methionine, Threonine, Alanine, Aspartic Acid, Valine (MTADV), called 5-MER peptide (5MP), inhibits the inflammation in DSS and TNBS mouse models of IBD, when subcutaneously injected or orally delivered. Similarly, 5MP inhibited the inflammation in mouse models of Multiple Sclerosis (MS) and Rheumatoid Arthritis (RA; Ref 2). As IBD, MS and RA share up-regulation of pathological Serum Amyloid A (SAA) (which fuels chronic inflammations), we predicted and then showed that 5-MP targets and hampers the pathological SAA, thus ameliorating SAA-associated inflammatory diseases by inhibiting the release of pro-inflammatory cytokines from SAA-activated innate-immunity cells. Now we focus on deciphering 5MP mechanism of action. To this end, we show that 1. Rats with Collagen-Induced Arthritis (CIA; the animal model of RA), in contrast to mice or man, do not produce under inflammatory conditions SAA. Therefore, 5MP, in the absence of the SAA target, cannot inhibits the rat CIA, that is almost identical to mouse CIA. This fact supports our prediction that SAA is a 5MP target. 2. SAA binds 5MP, as indicated by mass spectrometry. 3. Polymerized and aggregated forms of SAA are the pathological forms of SAA, generating inflammation and amyloidosis, the last could be a severe complication of Crohn’s (Ref 3). Co-Incubation with 5MP interferes with SAA polymerization and aggregation (Figure 1), providing mechanistic explanation for 5MP therapeutic effect in IBD. 4. Human Fibroblasts, monocytes and Peripheral Blood Mononuclear Cells (PBMCs), stimulated with human SAA, release the pro-inflammatory cytokines IL-6, IL-1β and TNFα. Co-incubation of SAA with 5MP (but not with scrambled peptide TMVAD) suppresses the cytokines release from the cells, providing evidence on the 5-MP potency to interfere with SAA-cytokine destructive cross-talk. In support, mice with IBD reduce inflammation and alleviate IL-6 and IL-1β expression in colonic tissue after 5-MP injection (Figure 2). 5. Normal immune responses, such as DTH or antibody response to foreign antigen, are not inhibited by 5MP. 6. 5-MP is stable in room temperature for at least 5 months. 7. Dogs can tolerate (without signs of harmful effects) 5MP doses, which are much higher than the 5MP therapeutic dose, and finally, a finding which merits a special attention 8. Gene Set Enrichment Analysis reveals that 5-MP activates genes, inducing resistance to IBD, e.g., Batf2, Fgl2, Ifitm3, Pyrin (Nefv), TNFR2 and Tnfrsf9.

1. Nedvetzki, S., and Naor, D. J. Clin. Invest. 111, 1211-1220, 2003. 2. Hemed-Shaked M. and Naor D. J Autoimmun. Aug 12;124:102713, 2021. 3. Denis MA. Eur J Clin Invest. 2013;43:292-301
CORTICOSTEROIDS AND 5ASA VERSUS CORTICOSTEROIDS ALONE FOR ACUTE SEVERE ULCERATIVE COLITIS: A RANDOMIZED CONTROLLED TRIAL
Authors: Ben-Horin Shomron , Har-Noy Ofir , Katsanos Konstantinos , Roblin Xavier , Chen Min-Hu , Gao Xiang , Schwartz Doron , Cheon Jae Hee , Cesarini Monica , Bojic Daniela , Protic Marijana , Theodoropoulou Angeliki , Abu-Kaf Heba , Engel Tal , Tang Jian , Veyrard Pauline , Lin Xiaoqing , Mao Ren , Christodoulou Dimitrios , Karmiris Konstantinos , Knezevic-Ivanovski Tamara
Published: January 2022

BACKGROUND

Corticosteroids are the mainstay of treatment for hospitalized patients with acute severe ulcerative colitis (ASUC). However, whether the addition/continuation of 5-aminosalicylates (5ASA) with corticosteroids during hospitalization is superior to corticosteroids alone is unknown

METHODS

This was a randomized controlled investigator-blinded clinical trial conducted in ten centers in six countries. Patients hospitalized with ASUC (Lichtiger score ≥10) were eligible. Patients received corticosteroids alone or corticosteroid+5ASA (4gr/day mesalamine) by a stratified randomization according to 5ASA use prior to admission. The primary outcome was the percentage of patients who responded to treatment by day 7, defined by a drop>3 points in the Lichtiger score and an absolute score<10 without the need for rescue medications or colectomy.

RESULTS

346 patients were screened and 149 were included (70/149 females, median age 41). Of these, 73 received corticosteriods+5ASA and 76 corticosteroids alone. For the primary outcome, 53/73 (72.6%) of patients receiving corticosteroids with 5ASA responded versus 58/76 (76.3%) of patients on corticosteroids alone (OR 0.82 95%CI 0.39-1.72, p=0.60). There was no difference between groups in duration of hospitalization or CRP normalization rate. Colectomy rate up to day 90 was similar, but the need for biologics among patients receiving combination corticosteroids with 5ASA was numerically lower by day 30 (p=0.11) and day 90 (p=0.07).

CONCLUSION

In this randomized controlled trial, combination 5ASA with corticosteroids did not benefit hospitalized patients with ASUC more than corticosteroids alone. An exploratory finding of a reduced need for biologics at 90 days in the combination group merits further evaluation.
WHEN CROHN’S COMES TO RADIOLOGIST- THE ROLE OF MR ENTEROGRAPHY (MRE) IN THE DIAGNOSIS OF PENETRATING CROHN’S DISEASE IN PEDIATRIC AND ADULT PATIENTS
Authors: Cyranka Weronika , Kuczynska Maryla , Zbroja Monika , Nowakowska Malgorzata , Piekarska Monika , Siejka Karolina , Grzegorczyk Magdalena
Published: January 2022

INTRODUCTION

Crohn’s disease is a chronic inflammatory disease of the gastrointestinal tract. The typical clinical scenario is a young patient presenting with abdominal pain, chronic diarrhea and fatigue. The diagnosis is typically made with endoscopic and/or radiologic findings. Nowadays, non-invasive imaging examination (like MRE) plays an increasingly important role.

AIM

The aim of the study is to assess the usefulness of the MRE in the diagnosis and monitoring of penetrating Crohn’s disease in comparison to adult and pediatric patients.

METHODS

The study included 146 adults (82 women and 64 men) and 23 pediatric patients (10 boys, 13 girls) diagnosed with Crohn’s disease, who underwent MRE with intravenous administration of a contrast agent. All MRE findings were further confirmed by colonoscopy, or intraoperatively if applicable.

RESULTS

In the adult group 30 fistulas were identified: 6 complex perianal, 16 simple intestinal (7 blind and 9 ileo-colonic) and 8 complex intestinal (3 ileo-cecal and 5 ileo-colonic). Peri-intestinal abscesses were observed in 9 patients. In the pediatric group in 5 patients small intestine fistulas were found, whereas abscess was observed in another 5 patients. In 12 children inflammatory infiltration of peri-intestinal fat was depicted.

CONCLUSION

In MRE, we can observe the entire intestinal wall, which allows for an accurate assessment of changes in the digestive system. Our research shows that the incidence of Crohn’s disease complications differs between adult and pediatric patients - perianal abscesses are diagnosed more often in children, while peri-intestinal location is more common in adults. The presence of fistulas was found with the same frequency in both study groups.
EFFICACY OF A DIGITALLY DELIVERED PERSONALIZED ELIMINATION DIET FOR THE SELF-MANAGEMENT OF INFLAMMATORY BOWEL DISEASE AND IRRITABLE BOWEL SYNDROME
Authors: Jactel Samuel , Olson Joseph , Brown Jordan , Wolin Kathleen , Jagiella Valerie
Published: January 2022

BACKGROUND

A large majority (60-80%) of Inflammatory Bowel Disease (IBD) and irritable bowel syndrome (IBS) patients report that symptoms originate from, or are exacerbated by “trigger foods”, and modify their diets to alleviate discomfort. Dietary interventions appear to be a reasonable complementary treatment to traditional clinical care. Despite demand, there is no consensus on what diet is best for IBD or IBS patients. Popular diets, such as the low-fermentable oligosaccharide, disaccharide, monosaccharide, and polyol diet (FODMAP) have notable limitations (e.g., implementation cost, length, complexity) and are not personalized to an individual.

OBJECTIVE

The purpose of this study was to evaluate the feasibility, desirability, and impact on gastrointestinal symptoms and quality of life (QoL) of a digitally delivered personalized elimination diet for IBD and IBS patients.

METHODS

This was a single-center open-labeled uncontrolled prospective cohort study. Participants were recruited online and were provided access to Agora Health, LLC’s digital personalized nutrition tool (N=37; CD = 9, UC = 12, IBS = 16). Over a period of 9 weeks, participants followed Agora’s 4-step elimination diet protocol: identification, elimination and reintroduction of trigger foods, followed by a maintenance phase. At baseline, daily, and at conclusion, symptom scores were calculated. The Patient-Based Simple Clinical Colitis Activity Index (P-SCCAI) and Mobile Health Index for Crohn’s Disease (mHI-CD) were used to calculate IBD disease severity. The Irritable Bowel Syndrome Symptom Severity Score (IBS-SSS) was used to assess IBS symptomatology. In addition to IBD & IBS symptoms, participants provided qualitative assessments of energy, stress, physical activity, and QoL.

RESULTS

The digital personalized elimination diet program improved symptoms and received strong positive reviews. Significant symptom improvement (p<0.05 two-tailed t-test, Bonferroni-corrected) was seen for 81% of participants at week 5 (phase 2) and persisted for 70% at week 9 (phase 4), measured by the relevant symptom severity score. Clinically significant symptom improvement (>25% reduction in P-SCCAI or mHI-CD scores, >35-point reduction in IBS-SSS) was observed in 78% of participants at week 5 and 62% at week 9. Ninety-five percent of participants felt more empowered and in control of their digestive health and 89% felt their quality of life improved due to the program. Sixty-two percent reported improved energy, 68% reported lower stress and 60% reported more physical activity after completing the program. Daily engagement was seen for 95% of participants and 92% were satisfied with the program.

CONCLUSIONS

Dietary elimination can improve symptoms in patients with IBD and IBS and digital tools can improve adherence and engagement. Randomized controlled trials are warranted.
ACUITY OF PEDIATRIC INFLAMMATORY BOWEL DISEASE ADMISSIONS PRE AND DURING THE COVID-19 PANDEMIC
Authors: Waschmann Malika , Stuart Ariana , Lin Henry , Hunter Anna
Published: January 2022

BACKGROUND

The COVID19 pandemic has introduced new challenges to the diagnosis and management of pediatric Inflammatory Bowel Disease (IBD). Many patients have had limited access to their providers through telemedicine and may choose to delay non-emergent treatment for fear of risking exposure in healthcare settings. Additionally, the “hygiene hypothesis” would suggest that decreased microbial exposure secondary to social isolation may result in greater incidence of new IBD diagnoses and worsened exacerbations of preexisting disease, particularly in urban populations. We hypothesize that these factors resulted in worsened disease status upon admission.

METHODS

We conducted a retrospective chart review of pediatric patients with IBD admitted to a tertiary care center before the onset of the COVID19 pandemic (01/01/18 – 03/01/20) and during the pandemic (03/01/20 – 08/01/21). All patients ≤18 yrs old who were admitted for a flare or new diagnosis of IBD were included. Variables collected included: demographics, admission indication, length of stay, laboratory markers of disease severity, surgical or endoscopic procedures performed during admission, and new treatments started on discharge. Data were analyzed using paired t-tests. Study was IRB approved.

RESULTS

The pre-COVID (N=50) and during-COVID (N=52) populations were similar in regard to demographic and clinical characteristics. More patients during-COVID19 underwent major surgical interventions (11.5% vs. 0%, p=0.007), and were started on biologic therapies or steroids (38.5% vs. 26%, p=0.09 and 11.5% vs. 0%, p=0.007 respectively). Length of stay was also increased during-COVID (5.5 days vs. 4.9 days, p=0.3). UC patients admitted during-COVID exhibited more severe thrombocytosis (483 vs. 419, p=0.2) while CD patients admitted during-COVID exhibited more severe anemia (10.7 vs. 11.6, p=0.1) and hypoalbuminemia (2.7 vs. 3.1, p=0.04). Although not significant, more patients during-COVID were admitted from urban areas (63.5% vs. 56%, p=0.2).

DISCUSSION

Increased length of stay and incidence of major surgical interventions and biologic therapy initiation suggest that pediatric patients admitted for a flare or new diagnosis of IBD during the COVID19 pandemic experienced worsened disease severity. More severe thrombocytosis, anemia, and hypoalbuminemia upon admission supports this correlation. We hypothesize that many families chose to delay presentation given fear of exposure to COVID19. Furthermore, partial department closures may have led to delays in seeing patients in-person and ultimately admission. Lastly, we suspect that during-COVID fewer patients were admitted from rural areas given they experienced less emotional stress and physical isolation than their urban peers. Uninterrupted exposure to farm animals and peers at school may have had a protective effect on microbiome balance and stress level.
INFLAMMATORY BOWEL DISEASE RISK STRATIFICATION AND MANAGEMENT IN A COMMUNITY PRACTICE SETTING
Authors: Collins Angelina , Swift Sadie , Recht Adam , Prime Rose , Topp Robert , Beltyukova Svetlana , Goldklang Robert , Gaylis Franklin
Published: January 2022

INTRODUCTION

Risk stratification of patients with Inflammatory Bowel Disease (IBD) is integral for patient management according to care pathways and IBD guidelines. We examined explicit IBD risk stratification and the extent of its influence on patient management in a community-based practice setting.

MATERIAL AND METHODS

This was a single-center, retrospective study of adult patients with IBD followed at Genesis Healthcare Partners between January 1, 2016 and December 31, 2018. 250 consecutive IBD charts were reviewed for (a) patient demographics; (b) disease characteristics; (c) explicit risk stratification and disease activity documented by clinician provider; (d) management and treatment. Patients were independently risk stratified based on AGA clinical care pathway risk factors (implicit risk stratification). CD high risk factors include: age under 30 at diagnosis, extensive anatomic involvement, perianal and/or severe rectal disease, deep ulcers on endoscopy, stricturing and/or penetrating behavior, prior surgical resection. UC high risk factors include age under 40 at diagnosis, extensive anatomic involvement, deep ulcers on endoscopy, high CRP and/or ESR, steroid requiring disease, C Difficile or CMV infection, prior hospitalization for UC.

RESULTS

211 eligible patients: 77 (36.5%) with Crohn’s Disease (CD) and 134 (63.5%) with Ulcerative Colitis (UC) were included; 52% female, 85% Caucasian, median age at diagnosis was 33 years, median length of CD was 16 years, and the median length of UC was 8 years. 18 (2%) had explicit risk stratification documented. Implicit risk stratification was: CD: 9 (12%) low risk [zero high risk factors], 68 (88%) high risk [one or more high risk factors].

UC: 27 patients (20%) low risk [zero high risk factors]; 107 patients (80%) high risk [one or more high risk factor]. Medication management for low-risk CD: 5-ASAs: 5 (56%); locally acting steroids: 5 (56%); systemic steroids: 1 (11%); immunomodulators (IMM): 2 (22%); and biologics: 4 (44%) and high-risk CD: 5-ASAs: 17 (25%); locally acting steroids 18 (27%); systemic steroids 20 (30%); IMM: 21 (31%); biologics: 46 (69%). Medication management for low-risk UC: 5-ASAs: 24 (92%); locally acting steroids: 5 (19%); systemic steroids: 4 (15%); IMM: 2 (8%); biologics: and 1 (4%) and high-risk: 5-ASAs: 97 (91%); locally acting steroids: 42 (39%); systemic steroids: 45 (42%); IMM: 16 (15%); biologics: 44 (41%). Of 182 UC endoscopy procedures explicit Mayo endoscopic sub-scores was documented in 3 (2%). Implicit Mayo Scoring was: 21% Mayo 0, 34% Mayo 1, 26% Mayo 2 and 16% Mayo 3.

CONCLUSIONS

Explicit risk stratification and Mayo endoscopy scoring was infrequently documented. Embedding risk stratification tools and standardized Mayo endoscopy scoring into EMRs would help to standardize documentation.
CROHN’S DISEASE AND ACUTE PANCREATITIS; ASSOCIATION, OUTCOMES, AND PREDICTORS OF 90-DAY READMISSION WITH ACUTE PANCREATITIS. INSIGHTS FROM THE NATIONWIDE READMISSION DATABASE
Authors: Abomhya Ahmed , Clemeston Elizabeth , Gayam Vijay , Khan Farrah , Etienne Denzil
Published: January 2022

INTRODUCTION

It’s a controversy if pancreatitis can be considered one of the extraintestinal manifestations of Crohn’s disease (CD). (Barthet et al AJG) CD patients have a fourfold increase in the risk of acute pancreatitis (AP) compared to the general population. (Rasmussen et al Scan J Gastroenterol) The annual incidence of AP in the general population ranges from 13 to 45/100,000 persons. (Dhiraj et al Gastroenterology)

METHODS

We collected data from the publicly available Healthcare Cost and Utilization Project (HCUP) Nationwide Readmission Databases (NRD) 2017-2018. We identified individuals discharged with a diagnosis of CD or one of its complications. The case selection process is summarized in Figure 1. We studied the burden of AP in patients with Crohn’s disease, hospitalization outcomes, and predictors of hospital readmissions with AP. Median and IQR were used to describe Continuous variables, and proportions were used with categorical variables. Comparison between groups was performed by Mann Whitney test for continuous variables and Chi-Square test for Categorical variables. We performed a binary logistic regression analysis for predictors of 90-day readmission with AP. Statistical analyses were performed using SPSS Version 25 (IBM Corporation, Armonk, NY, USA).

RESULTS

We analyzed 147,501 index hospital discharges with Crohn’s disease or one of its complications, 0.9% had chronic pancreatitis, and 1.6% had a diagnosis of AP. Around 14% of AP was biliary, 13% was Alcohol-induced, 7% was drug-induced, while 66% was classified as idiopathic, other, or unspecified AP. Table 1 shows a Comparison between CD patients with AP and CD patients without AP. Having AP on index hospitalization wasn’t related to CD complication status as those without AP had a higher prevalence of complications (P values <0.001). After excluding those who died in index hospitalization, those with Chronic Pancreatitis, and those discharged in Oct-Dec, 0.3% of patients had 90-day readmission with AP. Characteristics of CD patients with 90-day readmission with AP are illustrated in Table 2. A binary logistic regression for predictors of 90-day readmission with AP is illustrated in Table 3. The chi-square test results indicate that our regression model is a significant improvement in fit relative to an intercept-only model (χ2= 498.489, p<.001).

CONCLUSION

AP is associated with higher morbidity and mortality in patients with CD. Age, number of comorbidities, and having AP in index hospitalization are significant predictors of 90-day readmission with AP. Further biochemical studies would be needed to investigate the association between AP and CD. The study was limited by the lack of a specific ICD-10 code for autoimmune pancreatitis and the inability to account for common CD drugs associated with Pancreatitis.
ILEAL ENTEROCYTE BRUSH BORDER ABNORMALITIES ASSOCIATE WITH PROGRESSIVE DISEASE COURSE IN PEDIATRICS CROHN’S DISEASE
Authors: Haberman Yael , Vallance Jefferson , Baverman Julie , Liu Ta-Chiang , Kugathasan Subra , Denson Lee , Van Dussen Kelli
Published: January 2022

BACKGROUND

Biomarkers are needed to identify the subset of Crohn’s disease (CD) patients at-risk for severe, treatment-refractory disease. Short ileal microvillus length (MVL) is an epithelial biomarker that predicted non-response to treatment in adult CD. Here, we hypothesized that short MVL phenotype would occur in pediatric CD and associate with more severe disease.

METHODS

H&E-stained ileal tissue sections were obtained from 3 pediatric cohorts: WashU, CCHMC, and RISK (n=58 controls, n=377 CD). MVL was measured in regions not involved in acute inflammation. RISK had baseline “pre-treatment” and follow-up “post-treatment” sampling, clinical phenotyping, and transcriptomic data. Transmission electron microscopy (TEM) and immunofluorescence was performed on paired samples from 6 CD and 6 controls.

RESULTS

Ileal MVL was shorter in pediatric CD (mean: 1.44 μm) vs. controls (mean: 1.64 μm; P<0.0001). MVL did not associate with body mass index, disease location, endoscopic deep ulcers, or disease activity index scores. Histological inflammation scores were greater in baseline CD vs. controls, but similar between CD with short (defined as <1.46 μm, 10th percentile of controls) or normal MVL. Progression from B1 inflammatory disease behavior to B2 stricturing or B3 internal penetrating disease behavior was more likely to occur in patients with shorter MVL (n=91 follow-up samples collected prior to disease progression event; B2: P=0.0077, B3: P=0.0186). Additionally, progression to B2 occurred sooner in those with short follow-up MVL (P=0.0206). In contrast, associations with disease behavior progression based on baseline MVL were not observed. RNA-seq analysis identified 92 genes differentially expressed between CD and controls and correlated with MVL. Gene function analysis showed enrichment (P<0.001) for actin cytoskeleton, transporter activity, and plasma membrane among the 43 genes positively associated with MVL, and enrichment for myeloid cell, response to bacterium, and extracellular matrix among the 49 genes negatively associated with MVL. TEM showed thinning of the terminal web in CD, with diminished microvillus rootlet length and organelle-free zones, features associated with shortened or disorganized microvilli in mouse models. We next assessed terminal web-associated proteins, PLS1 and MYH14, and found that both were altered in CD samples; PLS1 was abnormally enhanced at the brush border, and MYH14 was aberrantly localized in the cytoplasm. Misexpression of MYH14 was associated with terminal web thinning and shorter MVL.

CONCLUSIONS

This study supports short ileal MVL phenotype in follow-up CD samples as an epithelial biomarker for more severe disease prognosis, particularly for progression to stricturing disease. Our data suggest that terminal web alterations underlie the short MVL phenotype.
FECAL MICROBIOTA OF PEOPLE WITH CROHN’S DISEASE DOES NOT CHANGE WITH ILEOCECAL RESECTION
Authors: Moutsoglou Daphne , Khoruts Alexander , Vaughn Byron
Published: January 2022

INTRODUCTION

Up to 80% of people with ileal Crohn’s disease (CD) will require an ileocecal resection (ICR). CD recurrence following surgery is common, although antibiotics can reduce short term recurrence rates. Following an ICR, it is unknown what happens to the fecal microbiota and how the microbiota relates to CD recurrence. To further investigate this, we analyzed fecal microbiomes of patients with CD (with and without an ICR) and compared to healthy controls.

HYPOTHESIS

Patients with CD and active inflammation have more dysbiosis of their fecal microbiomes, and ileocolonic resection (ICR) improves this dysbiosis.

METHODS

We performed a cross sectional study of fecal samples patients with CD (stratified by ICR status) and healthy controls. DNA was isolated and the V4 hypervariable region of the 16S rRNA gene was amplified and sequenced using the Illumina platform. Ecological metrics were applied to characterize fecal microbiomes. In our comparison, CD patients were further stratified based on their most recent colonoscopy into the following groups: 1) history of ICR versus surgically naïve CD patients, 2) active inflammation (in either the ileum and/or colon), and 3) active ileal inflammation versus none (colonic inflammation excluded).

RESULTS

Twenty-four CD patients (n=14, 58 % with ICR) and 38 healthy controls provided fecal samples. Global trends demonstrated that CD patients have significantly reduced richness (or observed taxonomic units) (Figure 1 A, p<0.0001) and significantly reduced Shannon diversity indices (Figure 1 B, p<0.0001) in their fecal microbiomes compared to healthy controls. Community diversity based on principal component analysis of Bray-Curtis pairwise dissimilarity indices is shows distinct clustering between healthy controls and CD patients (Figure 1 C). Richness and Shannon diversity index is not significantly different between CD patients that are surgically naïve compared with those that have undergone ICR (Figure 2 A and B). Richness and Shannon diversity indices are not significantly different between CD patients without versus with active inflammation (Figure 2 C and D) and is also not significant in CD patients without vs with ileal inflammation (Figure 2 E and F).

CONCLUSION

CD is characterized by fecal microbiota dysbiosis. ICR did not impact the fecal microbiota and fecal samples could not distinguish ileal inflammation. ICR paired with therapies to improve dysbiosis may affect CD recurrence.
REAL WORLD EFFECTIVENESS AND SAFETY OF OZANIMOD: INITIAL RESULTS FROM A LARGE TERTIARY CENTER
Authors: Cohen Nathaniel , Choden Tenzin , Choi David , Cleveland Noa , Cohen Russell , Dalal Sushila , Sakuraba Atsushi , Hanan Ira , Rubin David
Published: January 2022

BACKGROUND

In May 2021 the United Stated Food and Drug Administration (FDA) approved the use of ozanimod for moderate to severe ulcerative colitis (UC) based on the results of the pivotal phase 3 TRUE NORTH trials. We present the first report of real world data describing the use of ozanimod in clinical practice.

METHODS

This prospective, observational cohort study includes consecutive patients with active UC who initiated ozanimod at our center following FDA approval. We collected demographic, clinical, and laboratory data. Clinical disease activity was assessed using the Simple Clinical Colitis Activity Index (SCCAI). Clinical response was defined as a decrease in ≥3 points in SCCAI from baseline, and clinical remission was defined as an SCCAI score of ≤ 2. Adverse events were extracted from the electronic medical records (EMR) and regular clinical pharmacist follow up.

RESULTS

18 patients have initiated ozanimod therapy at our center. We observed 15 patients with UC, 1 patient with indeterminate colitis (IC), 1 patient with Crohn’s colitis, and 1 patient with lymphocytic colitis. All patients were included in the safety analysis and only patients with UC or IC were included in the effectiveness analysis. The mean age was 44.7 ± 18.5 with a mean age at disease duration of 9.6 ± 10.4. Ten (62%) patients were male, most patients 11 (69) had left sided colitis; 12 (75%) had previous biologic exposure. Additional demographics are described in Table 1. At week 4, follow up was available for 11 patients. Among these, 7 (64%) patients demonstrated clinical response, 2 (18%) were in clinical remission, and 1 patient achieved corticosteroid (CS) free remission. At week 8, follow up data was available for 7 patients; 3 (43%) patients had a clinical response and 1 (14%) patient achieved CS free remission (Figure 1A). 7 patients had complete blood counts at weeks 0 and 4, and all of these patients had a reduction in absolute lymphocyte counts (mean ± SD 1.46±0.47 109 cells/liter) (Figure 1B). There were 5 adverse events during the follow up period, none of which required treatment cessation. 1 patient had self-limited gastroenteritis, 1 patient had transient fatigue and another transient nausea. 1 patient developed mild liver enzyme derangement. 1 patient had non-specific chest pain and therapy was paused for a day until investigations returned negative.

CONCLUSION

This is the first real world data from a relatively treatment refractory cohort of UC patients and shows promising effectiveness and safety of ozanimod. Longer follow-up in larger patient cohorts is required to assess ozanimod’s role in clinical practice.
SUCCESSFUL CLEARANCE OF CYTOMEGALOVIRUS COLITIS IN ACUTE SEVERE ULCERATIVE COLITIS DURING INDUCTION OF OZANIMOD
Authors: Mohamed Rana , Kern Cody , Fein Aaron , Barrett Terrence , Perry Courtney
Published: January 2022

INTRODUCTION

Cytomegalovirus (CMV) colitis, commonly observed in patients with acute severe ulcerative colitis (UC), increases the risk for colectomy and treatment resistance. Unfortunately, corticosteroids and immunomodulators increase CMV reactivation and infection. The use of certain biologics such as anti-TNF mAb increase the risk for CMV colitis, while experience with newer biologics is limited leaving clinicians with few validated options. Ozanimod, an oral sphingosine-1-phosphate receptor modulator, was recently approved for induction and maintenance therapy for UC. Experience with ozanimod in the setting of UC complicated by CMV infection has not been reported to this date. We report here on a severe UC patient with tissue proven CMV ulceration that cleared the viral infection during ozanimod induction.

CASE REPORT

A 21-year-old male with UC treated with tofacitinib presented with five days of diffuse abdominal pain and 10-12 episodes of bloody diarrhea per day with CRP 341mg/L (<8.0mg/L) and calprotectin >3000μg/g (<49μg/g). Computed topography of the abdomen and pelvis showed diffuse wall thickening and mucosal enhancement throughout the entire colon and rectum. He was started on methylprednisolone 20mg TID for acute severe UC. He previously failed infliximab, adalimumab, ustekinumab, and vedolizumab. Colonoscopy showed pancolitis (Mayo score 3) with deep ulceration in the cecum. Random colon biopsies were consistent with active colitis with an area of CMV infection in an area of cecal ulceration (Figure 1). Serum CMV Quantitative PCR was 410IU/ml (normal <50IU/ml). The patient refused colectomy and was started on IV ganciclovir 5mg/kg q12h while transitioning to prednisone 40mg/day. Three weeks after initial presentation and eleven days after starting ganciclovir, the patient began ozanimod. He remained on ganciclovir for three weeks then transitioned to oral valganciclovir 900mg BID. The patient’s symptoms improved, CRP normalized, and calprotectin levels dropped (1200μg/g). Repeat colonoscopy performed eighteen days after ozanimod initiation revealed moderately-improved pancolitis (Mayo 2) with multiple healing cecal ulcers. Analysis of cecal ulceration IHC and peripheral blood PCR indicated clearing of the infection from the colon (Figure 2).

DISCUSSION

Cytomegalovirus colitis remains a common complication in severe UC, while avoidance of colectomy with viral clearance remains a challenge. Ozanimod and ganciclovir were chosen by this patient after refusing surgical resection. The improvement in clinical biomarkers of colitis and viral clearance suggest that ozanimod given with ganciclovir may be an exciting rescue therapy in these patients. Future studies will be needed to ascertain the rates of ozanimod response and CMV clearance in a larger patient cohort.
Preliminary Evidence on the Association of Complementary and Integrative Health Care Program Participation and Medical Cost in Veterans
Authors: Haun Jolie N , Paykel Jacquelyn , Fowler Christopher A , Lapcevic William A , Panaite Vanessa , Alman Amy C , Melillo Christine , Venkatachalam Hari H , French Dustin D
Published: January 2022

Introduction

Transforming Health and Resilience through Integration of Values-based Experiences (THRIVE) is a complimentary and integrative health program. THRIVE is delivered through shared medical appointments where participants engage in provider-led education and group discussion on wellness-related topics. THRIVE has been associated with improved patient-reported outcomes in a female veteran cohort. This quality improvement study evaluated the association between THRIVE participation and Veterans Health Administration (VHA) healthcare costs across a 1 year period.

Materials and Methods

A cohort study design (n = 184) used VHA administrative data to estimate the cost difference between 1 year pre- and post-THRIVE participation. The 1 year post-cost of the THRIVE cohort was then compared to the 1 year cost of a quasi-experimental waitlist control group (n = 156). Data sources included VHA administrative and electronic health records.

Results

Patients were roughly 51 years old, were typically White/Caucasian, and had a service priority level representing catastrophic disability. The adjusted post-THRIVE cost was $26,291 [95% confidence interval (CI): $23,014–29,015]; $1,720 higher than the previous year’s cost but was not statistically significant (P = 0.289). However, a comparison between the THRIVE cohort and a group of waitlist THRIVE patients (n = 156) the intervention group on average was $8,108 more than the waitlist group (95% CI: $3,194–14,005; P < 0.01).

Conclusions

In summary, data analysis of veterans’ annual healthcare cost trajectories were inconclusive. This preliminary study produced mixed results requiring more research with larger samples and randomized control trial methodology. Evidence of whether the THRIVE intervention can maintain cost effectiveness while maintaining its supported evidence of healthcare quality is needed.
Perceptions of Telemedicine and Costs Incurred by a Visit to a General Infectious Diseases Clinic: A Survey
Authors: Evers Emily C , Fritz Stephanie A , Colditz Graham A , Burnham Jason P
Published: January 2022

Background

The costs of attending in-person general infectious diseases clinics and preferences for visit type (telemedicine vs in-person) are not well known. We aimed to measure the time-related, monetary, social, and societal costs associated with travel to an in-person clinic visit and to assess patients’ preferences, questions, and concerns regarding telemedicine.

Methods

Patients (≥18 years, living ≥25 miles from clinic at time of clinic visit) were recruited for this survey study from the general infectious diseases (ID) clinic at Washington University from June 2019 to February 2020. We calculated time and money potentially saved by telemedicine, as well as carbon dioxide emissions, with the assistance of Google Maps (low/high estimates). We also determined patient preferences regarding telemedicine for ID care.

Results

Seventy-five patients completed the study. The round-trip mean travel distance was 227.2 ± 142.6 miles, mean travel time was 3.6 ± 2.0 hours to 4.5 ± 2.3 hours (low and high estimates from Google Maps), travel costs were $131.34 ± $82.27, and mean carbon dioxide emissions were 91.79 ± 57.60 kg. Fifty-eight patients (77.3%) said they would be willing to have a telemedicine visit in the future, and 30 (40.5%) said they would rather have had their visit the day the survey was completed as a telemedicine visit.

Conclusions

Telemedicine has the potential to significantly reduce patient costs, both monetary and time-related, and offers substantial environmental benefits, while being an acceptable method of care delivery to most patients at a general ID clinic.
COVID-19, policy change, and post-pandemic data governance: a case analysis of contact tracing applications in East Asia
Authors: Li Veronica Q T , Ma Liang , Wu Xun
Published: January 2022

In an era of digitalization, governments often turn to digital solutions for pressing policy issues, and the use of digital contact tracing and quarantine enforcement for COVID-19 is no exception. The long-term impacts of the digital solutions, however, cannot be taken for granted. The development and use of data tools for pandemic control, for example, may have potentially detrimental and irreversible impacts on data governance and, more broadly, society, in the long run. In this paper, we aim to explore the extent to which COVID-19 and digital contact tracing have led to policy change in data governance, if at all, and what the implications of such change would be for a post-COVID world. We compare the use of contact tracing and monitoring applications across mainland China, Hong Kong, and Singapore to illustrate both the enormous benefits and potential risks arising from the design of contact tracing applications and the involvement of stakeholders in the various stages of the policy cycle to combat the COVID-19 pandemic. We argue that, while COVID-19 has not changed the nature of issues, such as public trust in data governance, the increasing involvement of big tech in data policies, and data privacy risks, it has exacerbated those issues through the accelerated adoption of data technologies.
Predicting mechanical ventilation effects on six human tissue transcriptomes
Authors: Somekh Judith , Lotan Nir , Sussman Ehud , Yehuda Gur Arieh
Published: January 2022

Background

Mechanical ventilation (MV) is a lifesaving therapy used for patients with respiratory failure. Nevertheless, MV is associated with numerous complications and increased mortality. The aim of this study is to define the effects of MV on gene expression of direct and peripheral human tissues.

Methods

Classification models were applied to Genotype-Tissue Expression Project (GTEx) gene expression data of six representative tissues– liver, adipose, skin, nerve-tibial, muscle and lung, for performance comparison and feature analysis. We utilized 18 prediction models using the Random Forest (RF), XGBoost (eXtreme Gradient Boosting) decision tree and ANN (Artificial Neural Network) methods to classify ventilation and non-ventilation samples and to compare their prediction performance for the six tissues. In the model comparison, the AUC (area under receiver operating curve), accuracy, precision, recall, and F1 score were used to evaluate the predictive performance of each model. We then conducted feature analysis per each tissue to detect MV marker genes followed by pathway enrichment analysis for these genes.

Results

XGBoost outperformed the other methods and predicted samples had undergone MV with an average accuracy for the six tissues of 0.951 and average AUC of 0.945. The feature analysis detected a combination of MV marker genes per each tested tissue, some common across several tissues. MV marker genes were mainly related to inflammation and fibrosis as well as cell development and movement regulation. The MV marker genes were significantly enriched in inflammatory and viral pathways.

Conclusion

The XGBoost method demonstrated clear enhanced performance and feature analysis compared to the other models. XGBoost was helpful in detecting the tissue-specific marker genes for identifying transcriptomic changes related to MV. Our results show that MV is associated with reduced development and movement in the tissues and higher inflammation and injury not only in direct tissues such as the lungs but also in peripheral tissues and thus should be carefully considered before being implemented.