bluuebunny/crossref_metadata_2025_split huggingface dataset:
POINT-OF-CARE INTESTINAL ULTRASOUND FOR THE DETECTION OF POSTOPERATIVE CROHN’S DISEASE ENDOSCOPIC RECURRENCE
Authors: Dolinger Michael , Stauber Zachary , Spencer Elizabeth , Kayal Maia , Pittman Nanci , Colombel Jean-Frederic , Dubinsky Marla 
Published: January 2022

Abstract

BACKGROUND
In patients with Crohn’s disease (CD), following an ileocolic resection (ICR), colonoscopy is the gold standard for the detection of endoscopic recurrence (ER). Colonoscopy, however, is invasive and not easily accepted by patients for repeated monitoring. In contrast, transabdominal intestinal ultrasound (IUS) is non-irradiating, non-invasive, and easy to repeat. The goal of this study was to assess the accuracy of IUS for ER in CD.

METHODS
This was a cross-sectional study of CD patients who underwent point-of-care IUS during a postoperative follow-up clinic visit within 30 days of a planned colonoscopy. Parameters on IUS included bowel wall thickness (BWT), bowel wall hyperemia (BWH), layer stratification, inflammatory fat, lymphadenopathy, and complications. C-reactive protein (CRP), fecal calprotectin (FC), endoscopic healing index (EHI) and Harvey Bradshaw Index (HBI) were also measured. ER was defined as a Rutgeerts Score (RS) ≥ i2. Primary outcome was the association between IUS parameters and ER. Secondary outcomes were the association of IUS parameters with other markers of disease activity. Univariable analysis – Fisher’s exact, Wilcoxon Rank Sum and Spearman correlation coefficient tested associations with ER. Area under the receiver operator curve (ROC) was used to determine optimal cut-off values for BWT to accurately identify ER.

RESULTS
Eighteen CD patients (9 female; 29 [19-40] years old), underwent IUS examination 45 [29-99] months post-ICR. All patients underwent endoscopy within 30 days of IUS examination, four (22%) for the first time post-ICR. Seven (39%) patients were on ustekinumab, four (22%) on adalimumab, two (11%) on infliximab, one (6%) on vedolizumab, and four (22%) on no therapy. ER was found in eight (44%) patients. BWT and BWH in the neo-terminal ileum and BWH at the ileocolic anastomosis were the only IUS parameters associated with ER (Table 1). BWT was 4.0 [3.2-4.8] mm in patients with ER vs. 2.0 [1.5-2.6] mm without (p=0.04). Neo-terminal ileum BWH was abnormal in six (75%) patients with ER vs. 0% without (p=0.007). BWT of 3.2 mm was the optimal cut point for predicting ER with an: AUROC of 0.82, positive predictive value of 100%, negative predictive value of 97.3%, sensitivity of 75%, and specificity of 100% (Figure 1) vs. a CRP of 10.4 mg/L (AUROC = 0.54) or FC of 1146 μg/g (AUROC = 0.56). Significant correlations were observed between neo-terminal ileum BWT and RS (ρ=0.51, p=0.04) and between BWT and CRP (ρ=-0.56, p=0.023), but not BWT and FC (ρ=-0.04, p=0.91), BWT and EHI (ρ=-0.04, p=0.91), or BWT and HBI (ρ=0.09, p=0.75).

CONCLUSIONS
IUS is a feasible, accurate, non-invasive monitoring tool for detection of postoperative CD recurrence. Larger prospective studies are needed to determine how IUS can be integrated in the monitoring of CD patients after surgery.
ANEMIA TREATMENT PATTERNS AND OUTCOMES AMONG A NATIONAL COHORT OF PATIENTS WITH INFLAMMATORY BOWEL DISEASE
Authors: Brooks Carolyn , Sansgiry Shubhada , Hou Jason 
Published: January 2022

Abstract

BACKGROUND
Anemia is a common complication of inflammatory bowel disease (IBD) and can have a significant negative impact on quality of life by causing fatigue and reduced exercise tolerance. However, system wide patterns of anemia recognition and treatment are lacking. The aim of our study is to identify practice patterns of screening for anemia, assessment of iron stores, and administration of iron repletion therapy among a national cohort of patients with IBD.

METHODS
We conducted a retrospective cohort study of patients with IBD in the national Veterans Affairs (VA) dataset from 2000-2017. IBD patients were identified using a previously validated algorithm using administrative codes for Crohn’s disease (CD) and ulcerative colitis (UC). Laboratory values, patient demographics, and medical treatment data were extracted from the national VA datasets. Anemia was defined as hemoglobin &lt; 13 g/dL in males and &lt; 12g/dL in females. Initial observation of anemia during the study period was considered index anemia date. Analyses were descriptive of proportion of IBD patients with anemia, treatment, or outcomes. Temporal trends were presented as number patients by calendar year.

RESULTS
Of the 89,687 patients with IBD identified from 2000-2017, 50,781 (56%) were found to have anemia at least once during the study period. The number of IBD patients with anemia increased five-fold during the study period from 3,260 to 15,579 unique patients per calendar year. Testing for iron deficiency among patients with anemia was low- only 36% of anemic patients had iron studies completed within 6 months of anemia result. Of anemic patients who completed iron studies, the vast majority (89%) were consistent with iron deficiency anemia. Of patients with low iron stores, only 23% of patients received iron therapy within 6 months of lab result. Of patients with anemia, only 19% had anemia resolve within 1 year. Hospitalization within 5 years was observed in 30% of patients with anemia, with 60% of hospitalizations occurring within 1 year of index anemia date. IBD-associated surgery within 5 years of index anemia date was observed in only 2% of patients.

CONCLUSIONS
In a large national cohort of IBD patients, anemia is a common and undertreated complication, and is frequently followed by hospitalization and steroid use. Although iron deficiency is the most common cause of anemia, adequate iron testing and treatment is lacking, which may contribute to the low rates of anemia resolution. Interventions to improve anemia testing and treatment for iron deficiency anemia are needed.
CHRONIC COLITIS IN MICE INDUCES KIDNEY INJURY: TRANSLATIONAL IMPLICATIONS FOR IBD
Authors: Ducasa Gloria , Hazime Hajar , Fernandez Irina , Brito Nivis , Santander Ana , Burgueno Juan , Abreu Maria 
Published: January 2022

Abstract
Approximately 4-23% of patients with IBD develop renal complications such as nephrolithiasis, glomerulonephritis, and tubulointerstitial nephritis, which may lead to chronic kidney disease (CKD). Furthermore, it has been shown that younger age of IBD diagnosis increases risk for CKD development and this association is not linked to use of common therapeutic agents for the treatment of IBD, suggesting a disease mediated association of IBD to CKD. IBD is characterized by increased intestinal epithelial permeability. Interestingly, recent literature suggests that gut microbiome regulation plays a role in the development of CKD progression. However, the mechanisms contributing to IBD-mediated CKD have yet to be elucidated. We aimed to establish a model of colitis-mediated kidney injury and to elucidate the role of the microbiome on IBD-mediated CKD development.
Two distinct mouse models were used. BL/6 mice were treated with 2% dextran sodium sulfate for 6 days and euthanized, emulating an acute colitis model (A-DSS). We also utilized a chronic colitis model where BL/6 mice underwent three, five-day cycles of 2% dextran sodium sulfate (C-DSS) with a five-day recovery in between each cycle. Spot urines were collected on a weekly basis for albuminuria analysis. Kidneys and intestines were harvested at time of euthanasia. RNA was extracted for gene expression analysis and tissue samples were collected for histological assessment with oil-red-o (ORO) for lipid droplet analysis.
A-DSS mice did not experience any difference in kidney inflammatory markers, although intestinal inflammation was increased, as compared to control mice. A-DSS mice also did not demonstrate any difference in bacterial translocation to the kidney. Conversely, C-DSS mice (n=7) experienced an increase in inflammatory genes (IL1B and TNF) both in RNA extracted from colon and kidney sections as compared to control mice (n=4). C-DSS mice (n=3) demonstrated increased bacterial translocation (p=0.0003) to the kidney which was associated with increased albumin to creatinine ratios (p=0.0076) as compared to control mice (n=3). ORO staining of whole kidney sections demonstrated that C-DSS mice have increased lipid content as compared to control mice.
These data demonstrate that chronic colitis leads to changes in kidney inflammation and physiology seen in renal insufficiency including albuminuria. Furthermore, intestinal inflammation causes increased intestinal epithelial permeability and elevated bacterial translocation to the kidney, which has not been previously described. These data suggest that IBD may increase inflammation in a remote organ possibly through bacterial translocation. Additional studies are underway to identify if this colitis-mediated kidney injury is due to overall bacterial burden or specific bacterial content.
MICROSCOPIC COLITIS IS ASSOCIATED WITH DECREASED BONE DENSITY: A SYSTEMATIC REVIEW AND META-ANALYSIS
Authors: Chaisidhivej Natapat , Jaroenlapnopparat Aunchalee , Ponvilawan Ben , Tantivit Nessa , Goldberg Michael E 
Published: January 2022

Abstract

INTRODUCTION
Although, microscopic colitis (MC) can be considered as spectrum of inflammatory bowel disease (IBD), MC is very different in many aspects; in terms of risk factors, symptoms, course of disease, treatment, and complication. Low bone mineral density (BMD) is previously known as complication of IBD. There are few data about MC and risk of bone density loss. We conduct this systematic review and meta-analysis to determine the association between MC and low BMD.

METHODS
A comprehensive literature review was conducted using the MEDLINE, and EMBASE databases through October 2021 to identify studies that demonstrated association between clinical outcomes of interest, MC and low BMD. Pooled odds ratio (OR) and 95% confidence interval (CI) were calculated using a random-effect, generic inverse variance method.

RESULTS
After two rounds of review, four studies met our eligibility criteria and were included in analysis. The result showed statistically significant association between MC and low bone density (pooled OR = 2.15, 95% CI: 1.06 - 4.38, p = 0.03) The forest plots and funnel plots are shown below.

CONCLUSIONS
Our meta-analysis found significant association between MC and low bone density. Therefore, this data may suggest that BMD screening could be applied for MC patients, and such patients may have benefit from calcium and vitamin D supplementation. Further studies should be done to determine the significance of this issue.
SEROLOGICAL RESPONSES TO SARS-COV-2 VACCINATION IN PATIENTS WITH INFLAMMATORY BOWEL DISEASE: A PROSPECTIVE COHORT STUDY
Authors: Quan Joshua , Ma Christopher , Panaccione Remo , Kanji Jamil , Tipples Graham , Sharifi Nastaran , van Huyssteen Michelle , Markovinovic Ante , Turnbull LeeAnn , Bindra Gurmeet , Mahoney Douglas , Ingram Richard , Hracs Lindsay , Coward Stephanie , Windsor Joseph , Buie Michael , Chan Melissa , Ferraz Jose , Lu Cathy , Mathivanan Meena , Novak Kerri , Seow Cynthia , Shukla Tushar , Kaplan Gilaad 
Published: January 2022

Abstract

BACKGROUND
The immune response of SARS-CoV-2 vaccines is uncertain in those with Inflammatory Bowel Disease (IBD) due to a diverse array of immune-modifying therapies that vary in the mechanism of immunosuppression.

AIM
We aimed to quantify the serological response to SARS-CoV-2 vaccines in those with IBD and determine antibody levels across varying therapeutic options.

METHODS
Individuals with IBD who received first and/or second dose of a COVID-19 vaccine (Pfizer-BioNTech, Moderna, and/or AstraZeneca) were assessed for serological response (2–4 weeks after first dose; 2–8 weeks after second dose and 8–18 weeks after second dose) using the SARS-CoV-2 IgG II Quant assay to the spike protein of SARS-CoV-2. The cohort was stratified based on age, sex, vaccine received, IBD type, IBD therapeutic, and prior confirmed diagnosis of COVID-19. The primary outcome was seroconversion defined as IgG levels of ≥50 AU/mL. Secondarily, we evaluated the geometric mean titer (GMT) with 95% confidence intervals (CI).

RESULTS
Table 1 describes the characteristics of individuals with IBD (n=464) with serological data following the first dose (n=266) and/or second dose (n=303) of a COVID-19 vaccine. After the first dose of the vaccine, 81.6% seroconverted, with the lowest first-dose conversion rates in patients taking anti-TNF monotherapy (79.7%), anti-TNF combination therapy (52.9%), and corticosteroids (50.0%) (Table 1). Overall, 98.4% of the cohort seroconverted within 2–8 weeks of the second dose, with 94.6% seropositive within 8–18 weeks of the second dose. Seroconversion after second dose was consistently high across all medication classes (range: 94.6%–100.0%), except for oral corticosteroids (62.5%). GMT levels significantly increased (p&lt;0.0001) from first dose (1679 AU/mL) to second dose at 2–8 week (7943 AU/mL) but fell significantly (&lt;0.0001) to 3565 AU/mL 8–18 weeks from second dose (Table 1, Figure 1). GMT levels 2–8 weeks after second dose were higher in those with prior COVID-19 (12,729 AU/mL), but lower in those receiving anti-TNF combination therapy (4231 AU/mL) and oral corticosteroids (5996 AU/mL) (Table 1).

CONCLUSION
Seroconversion rates following full-regimen vaccination are high in patients with inflammatory bowel disease across all medication classes except for anti-TNF combination therapy and oral corticosteroids. Antibody titres and seroconversion rates tend to decrease after 8 weeks post-full vaccination, which is consistent across medication classes.
NEW OXPHOS REGULATING COMPOUND – AUPHOS – INCREASES MITOCHONDRIAL COMPLEXES EXPRESSION IN MURINE AND HUMAN INTESTINAL EPITHELIAL CELLS
Authors: Elsayed Ahmed , Abomhya Ahmed , Avdiushko Margarita , Kapur Neeraj , Awuah Samuel , Barrett Terrence , Goretsky Tatiana 
Published: January 2022

Abstract

INTRODUCTION
Mitochondrial dysfunction in intestinal epithelial cells (IEC) is a critical driver in the failure to heal chronic ulceration in IBD(1). OXPHOS is important for differentiation and cell polarity in repairing IEC(2,3). The development of new IBD drugs that improve mitochondria function would potentially accelerate mucosal repair and enhance overall clinical management of refractory patients. For this study, we tested the efficacy of a novel oral agent (AuPhos) that localized to mitochondria where it increases respiration (Wempe et al CCC, 2022) and mitochondrial energy production.

METHODS
Colonic IEC proteins from control and AuPhos-treated DSS mice were examined as described elsewhere (Wempe et al CCC, 2022). Both human biopsy and tissues from mice with reduced IEC mitochondria [VilCre/mTmG/TFAMfl/fl (IEC-TFAM-/-)](Abomhya et al CCC 2022) were incubated with AuPhos (0.2; 0.5; 1 μM for biopsies and 0.5 μM for mice) or vehicle for 3 hrs. at +4oC with rotation. N=4 mice/group.

RESULTS
In membranous IEC fractions of control mice, AuPhos increased protein expression of mitochondrial complexes (Mito-Cpx) (V – 50%, III – 52%, IV – 40%). DSS treatment decreased baseline expression dramatically (V – 62%, III – 56%, II - 69%; IV – 75%). AuPhos in DSS mice increased expression of complex V by 48%, III – 35%, II – 68%, IV – 55% {A,B}. Expression of transcriptional factors PGC1a and Nrf2, which regulate mitochondria biogenesis, were increased in nuclear IEC fractions of DSS mice by 50% and 43% respectively {C,D}. Mito-Cpx and TFAM levels increased in AuPhos-treated human biopsies in a dose dependent manner {E}. AuPhos normalized mitochondrial complex levels in tissue (3h) taken from mice with attenuated mitochondrial respiration (IEC-TFAM-/-).

CONCLUSION
AuPhos increases expression of mitochondrial complexes in human and in two different murine models. The results of biochemical signaling studies suggest increased mitochondrial respiration enhances PGC1a and Nrf2 levels which are upstream of TFAM, the major transcription factor for mitochondrial biogenesis. Our lab is currently investigating this novel compound as a means for improving mucosal metabolism and accelerating mucosal repair in IBD. (Wempe et al CCC, 2022)
1 Kugathasan, S. et al. Prediction of complicated disease course for children newly diagnosed with Crohn’s disease: a multicentre inception cohort study. Lancet389, 1710-1718, doi:10.1016/S0140-6736(1730317-3) (2017).
2 Rodriguez-Colman, M. J. et al. Interplay between metabolic identities in the intestinal crypt supports stem cell function. Nature543, 424-427, doi:10.1038/nature21673 (2017).
3 Schell, J. C. et al. Control of intestinal stem cell function and proliferation by mitochondrial pyruvate metabolism. Nat Cell Biol19, 1027-1036, doi:10.1038/ncb3593 (2017).
ALTERED MICROBIAL BIOGEOGRAPHY IN INNATE IMMUNE-MEDIATED COLITIS
Authors: Boger-May Antonia , La Torre Diana La , Ruley-Haase Katelyn , English Lauren , Roncagli Connor , Reed Theodore , Hoffman Hunter , Overstreet Anne-Marie , Boone David 
Published: January 2022

Abstract
We have developed an innate immune model of colitis that occurs in the absence of adaptive immunity, is early-onset, 100% penetrant, chronic, and dependent on microbes. villin-TNFAIP3 transgenic mice, crossed to RAG1-/- mice (aka TRAG mice) develop innate immune-mediated colitis that is not observed in villin-TNFAIP3 or RAG1-/- littermates. Antibiotic treatment prevents colitis in TRAG mice. Thus, we sought to investigate the microbes that drive chronic innate immune colitis in the absence of adaptive immunity. To examine the spatial organization of bacteria, mucus and intestinal epithelium, bacteria and mucus were localized in Methyl-Carnoys-fixed sections of WT, villin-TNFAIP3, RAG1-/- and TRAG colons and mucus layers were collected by laser capture microdissection (LCM) for evaluation of bacterial populations. To test antibiotic effectiveness in colitis prevention, TRAG mice were treated with single antibiotic solutions of ampicillin, neomycin, metronidazole, or vancomycin, or with all antibiotics combined in a cocktail, and colitis was scored along the proximal-distal axis of the colon. Microbial populations along the proximal-distal axis of the gut were compared between RAG1-/- and TRAG mice by 16S sequencing.
Microbial invasion of the mucus layer was abundant in villin-TNFAIP3 and in TRAG mice, but not WT or RAG1-/- mice. LCM indicated that a subset of microbes, of the classes Gammaproteobacteria and Actinobacteria, were over-represented in the mucus layer of TRAG mice. These included increased abundance of genera Serratia, Acinetobacter, Pseudomonas and Corynebacterium and decreased Bifidobacterium. Differences in antibiotic effectiveness were observed along the proximal-distal axis of the colon, with neomycin being most effective in prevention of inflammation in the cecum, while ampicillin was most effective in the distal colon. The proximal-distal communities of microbes in RAG1-/- mice were distinct and tightly grouped within the cecum, proximal colon, and distal colon, whereas this structure was lost in TRAG mice. In the RAG1-/- gut, the relative abundance along the proximal-distal axis decreased for Firmicutes (mainly Lachnospiraceae and Ruminococcacaea) and Proteobacteria (mainly Helicobacteriaceae and Desulfovibrionbacteriaceae) but increased for Actinobacteria (mainly Bifidobacteriaceae) and Bacteroidetes (mainly Bacteroidales). Unlike RAG1-/- mice, in TRAG mice the abundance of Bacteroidetes decreased along the proximal-distal gut axis. TRAG mice had higher abundance of Bifidobacterium animalis, Bacteroidetes acidifaciens and Lactobacilli and lower abundance of Lachnospiraceae, along the proximal-distal axis of the gut, compared to RAG1-/-mice.
The cross-sectional and proximal-distal biogeography of microbes in RAG1-/- mice is disrupted in TRAG mice, which may contribute to the innate colitis observed in this model.
GPX3 IS REQUIRED TO MEDIATE PROTECTIVE EFFECTS OF GPX1 LOSS IN COLITIS
Authors: Blunt Koral , Jacobse Justin , Allaman Margaret , Washington Mary , Goettel Jeremy , Wilson Keith , Williams Christopher , Short Sarah 
Published: January 2022

Abstract
Reactive oxygen species (ROS) have long been known to contribute to the development and severity of Inflammatory Bowel Disease. However, more recent data indicates ROS may not always be pathogenic, and in fact ROS may be necessary for intestinal homeostasis. Thus, the role of ROS in the intestine, and antioxidant proteins which regulate ROS, may be contextual and dose-dependent.
Members of the glutathione peroxidase (GPx) family are antioxidants that reduce hydrogen peroxide to water. Previously, we determined that loss of GPx1, the most widely expressed GPx, protected against dextran sodium sulfate (DSS)-induced colitis and augmented intestinal proliferation. To better understand how a stepwise increase in ROS may affect intestinal phenotypes, Gpx1-/- mice were next crossed with Gpx3 null mice to yield double-knockout (DKO) mice. First, we assessed baseline proliferation, apoptosis, and DNA damage in the colon. Interestingly, while Gpx1-/- mice displayed increased proliferation compared to WT mice, this was not observed in the DKO mice. Furthermore, Gpx1-/- mice had no change in apoptosis or DNA damage, yet both were increased in DKO mice. Together, these data suggest DKO mice lose the survival benefits of GPx1 loss upon greater reduction of antioxidant capabilities.
Next, we assessed the effects of combined GPx1 and GPx3 loss in the context of inflammation and colitis. At baseline, multiplex cytokine profiling identified higher levels of colitis-associated cytokines, including IL-12, CCL4, and CCL5, in DKO mice as compared to either Gpx1-/- or WT cohorts. Pro-inflammatory changes were more pronounced upon aging, as one-year-old DKO mice showed higher levels of TNF-α and IL-17, as well as histologic evidence of chronic inflammation which was absent in similarly aged WT mice. Next, we tested the effects of experimental DSS colitis. Here, while Gpx1-/- mice had less severe injury in the DSS colitis model, DKO mice showed more pronounced weight loss and a trend towards shortened colons as compared to WT mice. Finally, altered ROS-mediated signaling is known to impact interactions with the microbiota, and increased microbial diversity is associated with protection from colitis. To establish whether loss of GPx1 and GPx3 impacted the gut microbiome, stool was harvested from WT, Gpx1-/-, and DKO mice and bacterial DNA was assessed by 16S RNA sequencing. Interestingly, and in line with less severe colitis, Gpx1-/- mice had increased diversity and evenness compared to WT mice, whereas there was no change between WT and DKO mice. Taken together, these data indicate that GPx3 is required to mediate the anti-inflammatory effects of GPx1 loss. Furthermore, combinatorial GPx loss induces greater colonic inflammation at baseline and during DSS-induced colitis, highlighting dose-dependent effects of ROS and antioxidant capacity in the intestine.