bluuebunny/crossref_metadata_2025_split huggingface dataset:
COMPARATIVE EFFECTIVENESS AND SAFETY OF VEDOLIZUMAB AND ANTI-TUMOR NECROSIS FACTOR AGENTS IN OLDER ADULTS WITH INFLAMMATORY BOWEL DISEASES IN MEDICARE ADMINISTRATIVE CLAIMS DATABASE
Authors: Kochar Bharati , Pate Virginia , Kappelman Michael , Long Millie , Ananthakrishnan Ashwin , Chan Andrew , Sandler Robert 
Published: January 2021

Abstract

Background
The number of older adults with inflammatory bowel diseases (IBD) is increasing. Older adults with IBD are less likely to receive effective immunosuppression. We aimed to determine efficacy and safety of biologic therapies in older adults with IBD.

Methods
We conducted a retrospective cohort study using an active comparator, new user design in a 20% random sample from the 50 state Medicare claims database between May 2014 and December 2018. We included patients who initiated vedolizumab or an anti-tumor necrosis factor (TNF)-α agent (infliximab, adalimumab, golimumab or certolizumab) following 12-months of continuous enrollment in Medicare fee-for-service Parts A/B/D without either study drug. Patients were required to be ≥65 years old and have ≥2 international classification of disease (ICD) codes of Crohn’s disease (CD) or ulcerative colitis (UC). We excluded patients who received other biologic therapies and/or those who had ≥2 codes for other immunologic conditions. Pertinent co-variates included were age, sex, race Charlson Co-morbidity Index (CCI), predicted probability of frailty, healthcare utilization and baseline IBD medications. The outcomes of interest were hospitalizations, IBD-related surgery and new corticosteroid use ≥ 60 days after drug initiation. We described the study population, assessed health care utilization and use of other IBD medications. We estimated crude incidence rates and hazard ratios (HR) adjusted for the covariates using standardized mortality ratio (SMR) weights.

Results
We identified 488 vedolizumab users and 2,213 anti-TNF users. The median age was 72 years in the vedolizumab cohort and 71 years in the anti-TNF cohort; 12% of both cohorts were aged ≥80 years. Differences in the two cohorts existed with regards to sex, race, baseline healthcare utilization and IBD-related medications, but all the baseline differences were balanced by weighting measured by a standardized mean difference (SMD) &lt;0.1 (Table 1). After weighting, vedolizumab users were less likely to be hospitalized in the 12 months after biologic initiation (HR: 0.81, 95% CI: 0.68 – 0.96). While there was no significant difference in IBD related hospitalizations, older adults with IBD were less likely to have an infection-related hospitalization (HR: 0.39, 95% CI: 0.23 – 0.65). There were no significant differences in IBD related surgery and steroid use after induction (Table 2).

Conclusions
In this large, retrospective cohort study of older IBD patients who were new users of vedolizumab and anti-TNF agents, we found that older patients initiated on vedolizumab were significantly less likely to have an infection-related hospitalization. However, there were no significant differences in IBD-related hospitalizations, IBD-related surgery or corticosteroid use after biologic induction.
REINVENTING INFLAMMATORY BOWEL DISEASE (IBD) CLINICAL TRIAL RECRUITMENT USING NOVEL DIGITAL MEDICINE TOOLS
Authors: Fasihuddin Farah , Wedel Nicole , Atreja Ashish , Madisetty Divya , Jain Charu Madhwani , Rogers Jason , Atreja Ashish , Kakkar Sarthak , Garge Shashank 
Published: January 2021

Abstract

Background
Issues with patient recruitment and enrolment are the primary barriers for missed clinical trial timelines; 8 out of 10 clinical trials are delayed or unable to be completed because of the lack of timely patient recruitment. Current patient recruitment efforts are inefficient as they are typically dependent on the manual screening of patients during face-to-face visits. With the rapid development of digital communication platforms within healthcare and the broad consumer adoption of smartphones, there are increasing opportunities to overcome some of these barriers. Digital platforms have great potential for research and clinical care of chronic conditions, such as inflammatory bowel disease (IBD), an often debilitating disease that currently affects over three million adults in the United States. In this paper, we utilized a digital medicine platform (Trialengage, Rx.Health, New York, NY) to improve patient recruitment for an ongoing mindfulness trial which had limited success in face-face enrolment (16 patients over 6 months).

Methods
Patients enrolled in the Mount Sinai Crohn’s and Colitis Registry (MSCCR) were remotely outreached about enrolling in a mindfulness study for IBD patients. A text-based clinical rules engine was used to inform registry patients about the trial and to allow patients to indicate interest in participating via text message. Eligible IBD patients were bulk “prescribed” a notification through RxHealth’s digital medicine platform, RxUniverse. Characteristics of the enrolled population, characteristics of patients who responded, and timeliness of responses were analyzed.

Results
Of the 1364 patients in the MSCCR with available phone numbers, 270 patients affirmatively replied they wanted to participate in the study. Patients who opted-in to receiving more information about the study were more likely to have inadequate control of their IBD (25.64% vs 18.97%; P&lt;.05) and more likely to have a recent history of depression based on a validated patient health questionnaire (15.38% vs 8.4%; P&lt;.05) than those who opted-out. There were no significant differences in terms of race, gender, and age between the two groups. In terms of timeliness of response among those enrolled, the majority of patients responded within 2 hours of notification.

Conclusion
Digital medicine software platforms can facilitate large-scale, lower-effort recruitment of eligible patients for clinical trials. Future research should be done to explore their expanded use for recruitment, patient education, and study data collection. Additional technologies such as patient-powered networks, social media, e-recruiting bots, and other remote engagement platforms can aid clinical trials by saving time and reducing costs of patient recruitment.
ROLE OF CHEMERIN IN THE PATIENTS WITH INFLAMMATORY BOWEL DISEASES
Authors: Sochal Marcin , Fichna Jakub , Bialasiewicz Piotr , Talar-Wojnarowska Renata , Gabryelska Agata , Malecka-Panas Ewa 
Published: January 2021

Abstract

Background and aims
Chemerin belongs to adipokines, which are proteins secreted by white adipose tissue. It has important role in angiogenesis, metabolism and correlates with severity of inflammation. The study aimed to investigate the correlation between the serum level of chemerin and the severity of inflammatory bowel disease (IBD), and examine the influence of anti-TNF treatment on the chemerin level.

Methods
One-hundred and nineteen participants were recruited for this study: 77 with IBD and 42 healthy control (HC). Venous blood was collected from all study participants. Twenty-six patients, who underwent 14-week anti-TNF therapy were re-examined (infliximab or adalimumab). The measurements were performed by ELISA method, according to the protocol supplied by the producer. The study was funded by Medical University of Lodz Grant (#564/1-000-00/564-20-024).

Results
Serum chemerin level were higher in ulcerative colitis (UC) patients (557.4 ng/ml ±219.9) compared to Crohn’s disease (CD; 446.0 ±252.6; p=0.048). IBD patients (492.3 ng/ml ±244.3) achieved higher chemerin level than HC control (404.5 ng/ml ±194.2; p=0.047). Patients with IBD exacerbation (559.1 ng/ml ±235.6) achieved higher chemerin levels compared to remission (381.7 ng/ml ±220.2; p=0.002). Chemerin correlated with the severity of the clinical condition of the CD (Harvey-Bradshaw index; r=0.478, p=0.001), but not with the severity of UC (Partial Mayo Score; r=0.03, p= 0.788). Serum level of chemerin decreased after 14 weeks of anti-TNF treatment (519.6 ng/ml IQR: 393.2–727.0 vs. 351.5 ng/ml IQR: 229.3–424.2; p=0.002). Patients treated with steroids obtained higher concentrations of chemern compared to patients who did not receive such treatment (p=0.049).

Conclusions
Chemerin correlates with the clinical severity of IBD and its level lowers after anti-TNF treatment, which suggests its participation in inflammation. However, many factors affect its concentration thus it does not seem to present high diagnostic value or present as a possible therapeutic target.
IMMATURE LOW-DENSITY NEUTROPHILS AS MEDIATORS OF PYODERMA GANGRENOSUM AND INFLAMMATORY BOWEL DISEASE PATHOGENESIS
Authors: Jatana Samreen , Rebert Nancy , Fernandez Anthony , Achkar Jean-Paul , McDonald Christine 
Published: January 2021

Abstract
Pyoderma gangrenosum (PG) is a debilitating skin condition characterized by deep, pus-filled, non-healing ulcers packed with neutrophils and is a common extraintestinal manifestation of inflammatory bowel disease (IBD). Strikingly, ~40% of people with an initial presentation of PG go on to be also diagnosed with IBD, suggesting that both diseases have common factors driving their pathogenesis. The molecular and cellular mechanisms of PG and IBD co-development are currently unknown, hampering the development of effective treatment strategies for individuals affected by both diseases. Prior studies of individuals with PG demonstrate an enrichment of circulating immature low-density neutrophils (LDGs) that are sensitized to undergo NETosis, a specialized form of cell death. NETosis induces inflammation and, when dysregulated, can promote chronic cycles of inflammation. We hypothesize that LDGs mediate NETosis-driven inflammation in both PG and IBD, but the LDGs from individuals that develop both diseases are functionally distinct. In this translational study, blood samples are collected from healthy subjects or individuals with only PG, only Crohn’s disease, only ulcerative colitis, or individuals with both PG and IBD for the analysis of neutrophil populations, neutrophil function, as well as circulating markers of inflammation and NETosis. Preliminary data from 45 subjects demonstrate an enrichment of circulatory LDGs (CD45+ CD15+ CD66b+ CD10+ CD16+ cells from the low density fraction) in individuals with inflammatory disease as compared to healthy subjects (19.2% +/- 2.81%, n=41 vs. 9.9% +/- 2.9%, n=4; p=0.04). This is correlated with increased NETosis in vitro, however differences in the responsiveness of LDGs to priming signals, such as IL-1β, TNFα, and IL-6, are emerging between disease sub-groups. There is considerable variation in the levels of LDGs within disease sub-groups and analyses are underway to determine whether this variation correlates with subject reported disease activity, inflammatory markers (serum C-reactive protein), or circulating markers of NETosis (serum citrullinated histone 3). These preliminary findings point to the presence of a unique population of cells potentially contributing to inflammatory cross-talk between the skin and gut. Further analysis of these potentially disease driving cells may result in more effective care of IBD patients with extraintestinal manifestations, such as PG, through more mechanistically targeted therapeutic approaches, as well as potential biomarker discovery that predicts which PG patients are more likely to develop IBD leading to earlier intervention and better disease outcomes.
IS ILEOANAL POUCH EXCISION A DESTINATION THERAPY FOR INFLAMMATORY BOWEL DISEASE? DATA FROM A QUATERNARY POUCH REFERRAL CENTER
Authors: Choi Sarah , Lightner Amy , Lipman Jeremy , Hull Tracy , Steele Scott , Holubar Stefan , Rieder Florian 
Published: January 2021

Abstract

Background
Although ileal pouch-anal anastomosis (IPAA) is the surgical procedure of choice of many patients with ulcerative colitis and other conditions, some patients may require pouch excision (PE). We aimed to describe our experience with pouch excisions and associated outcomes with an emphasis on late medical, endoscopic, and surgical interventions for IBD.

Methods
We performed a retrospective review of a prospective colorectal surgery database. All PEs performed at our quaternary pouch center from 2006 – 2019 were included; pelvic exenteration, PE with neo-IPAA or Kock-pouch were excluded. Early complications occurred &lt;30 days, late complications &gt;30 days. Medications taken prior to PE were included if taken within 12 weeks of pouch excision. Data are reported in frequency (proportion) or median (interquartile range).

Results
A total of 197 cases met inclusion criteria, and were performed by 23 surgeons, median 6 excision (IQR 2 - 14) cases over a 14-year period: of these, 105 had their index pouch created at our quaternary pouch referral center (overall PE rate 2.7%). Indications for PE are shown in Table 1. Median time to PE was 7 years and 94 (48%) patients had re-diversion prior to PE. Medications prior to PE: 34 (17%) steroids, 27 (14%) biologics, and 22 (11%) immune-modulators. The median duration of surgery was 4 hours (3.2–5). The median estimated blood loss was 263 ml (150–500) with 24 patients (12%) requiring at least one unit of packed red blood cells intra-operatively. Most pouch excisions were done through laparotomy; 2 cases (1%) were started robotically and 11 cases (10%) laparoscopically with a 26% conversion rate. Intersphincteric dissection was used in 172 cases (87%) while 26 cases (13%) required abdomino-perineal resection, of which 58% had a neoplastic indication. Intra-operative, early and late complications are shown in Table 2; 40 patients (20%) had perineal wound complications in less than 30 days, while 26 patients (13%) had long-term perineal wound complications, of which 15 patients required return to the operating room. After PE, 23 patients (12%) required continuation of IBD medications, 6 patients (3.1%) required surgery, and 4 patients (2%) required endoscopic intervention for their IBD.

Conclusions
In this large series of ileoanal pouch excisions, we found that perineal wound complications are common, but infrequently require operative intervention. For most IBD patients in this series, pouch excision did appear to be a destination therapy for IBD with a small minority requiring ongoing medical therapy for IBD.
URINARY BLADDER NECROSIS - AN EXTRAINTESTINAL MANIFESTATION OF INFLAMMATORY BOWEL DISEASE IN A PEDIATRIC PATIENT
Authors: Norris Nicholas , Schlomer Bruce , Gurram Bhaskar 
Published: January 2021

Abstract
Extraintestinal manifestations are common in inflammatory bowel disease (IBD), and genitourinary complications are known, including nephrolithiasis, fistulas, and ureteral obstruction. Bladder involvement is less common, and limited to cystitis including xanthogranulomatous cystitis. Bladder necrosis has not been previously described in association with IBD. Here, we describe an unusual case of IBD associated with total bladder necrosis at the time of initial diagnosis.
An 8-year-old female with a history of chronic microcytic anemia presented with 1 week of hematochezia, hematuria, and fever with associated abdominal pain. Her exam was significant for mild lower quadrant abdominal tenderness including the suprapubic area, but was otherwise unremarkable. Blood work showed microcytic anemia and mild thrombocytopenia, elevated inflammatory markers, and hypoalbuminemia. Infectious workup was unremarkable. Upon admission, she developed oliguria and hypertension and rapidly progressed to renal failure requiring dialysis catheter placement and renal replacement therapy. A kidney biopsy revealed acute tubular injury but showed no glomerular involvement and had no evidence of hemolytic uremic syndrome or vasculitis. Imaging obtained including CT of her abdomen showed a thickened transverse colon and a thickened bladder wall with dilation of the renal collecting system, worse on the left. Bladder biopsy showed full-thickness necrosis of unclear etiology and had negative staining for microorganisms. She had bilateral nephrostomy tubes placed for drainage of her kidneys and her renal function subsequently returned to normal. MR imaging also revealed necrosis and confirmed complete bladder involvement. Her renal failure was presumed to be a secondary to ureterovesical junction obstruction from the bladder necrosis. She underwent esophagogastroduodenoscopy (EGD) and colonoscopy due to persistent hematochezia. The EGD was unremarkable. Her colonoscopy was grossly abnormal with evidence of colitis from the cecum to the rectum. Biopsies revealed both active and chronic inflammation with sparing of the terminal ileum, and immunohistochemical staining for infection was negative. Capsule endoscopy was largely unremarkable. She was diagnosed with ulcerative colitis and started on steroids and sulfasalazine. Her abdominal pain and stool consistency improved and her bloody stools resolved. Steroids were tapered and she continued sulfasalazine as maintenance therapy.
This case presents a novel association of IBD and bladder necrosis. Vascular obstruction secondary to a hypercoagulable state might explain such an event, but this seems less likely given the diffuse nature of bladder involvement. A clinical index of suspicion for bladder involvement and/or necrosis is warranted in patients with IBD who present with obstructive urinary symptoms or hematuria.
IDENTIFICATION OF SELETIVE CLAUDIN CATION CHANNEL BLOCKERS
Authors: Ma Jingjing , Wu Emma , Li Ye , Seibel William , Shen Le , Khalili Fatemeh , Weber Christopher 
Published: January 2021

Abstract
Compromised epithelial barrier function is known to be associated with inflammatory bowel disease (IBD) and may contribute to disease development. One mechanism of barrier dysfunction is increased expression of paracellular tight junction ion and water channels formed by claudins. Claudin-2 and -15 are two such channels. We hypothesize that blocking these channels could be a viable therapeutic approach to treat diarrhea. In an effort to develop blockers of these channels, we turn to our previously developed and validated in silico models of claudin-15 (Samanta et al. 2018). We reasoned that compounds that can bind with the interior of claudin pores can limit paracellular water and ion flux. Thus, we used docking algorithms to search for putative small molecules that bind in the claudin-15 pore.
AutoDock Vina was initially used to assess rigid docking using small compound databases. The small molecules were analyzed based on binding affinity to the pore and visualized using VMD for their potential blockage of the channel. Clusters of binding modes were identified based on the prominent interacting residues of the protein with the small molecules. We initially screened 10,500 compounds from within the UIC Centre for Drug Discovery and a cross-section of 10,000 compounds from the NCI open compound repository. This initial screen allowed us to identify 2 first-in-class selective claudin-15 blockers with efficacy in MDCK monolayers induced to express claudin-15 and in wildtype duodenum.
Next, we screened the entire NCI open compound repository for additional molecules structurally related to our best initially identified molecule and this has allowed us to identify 13 additional molecules that increase TER of claudin-15 expressing MDCK monolayers by 90–160%. Additionally, these molecules possess similar structural components that will be collected in a fragment library and explored through molecular dynamics simulations.
We also developed a claudin-2 homology model on which we are performing docking studies and in vitro measurements, which we expect will result in similar candidate ligands for blocking claudin-2. Our study will provide important insight into the role of claudin-dependent cation permeability in fundamental physiology, which we believe will lead to the utility of claudin blockers as a novel and much needed approach to treat diseases such as IBD.
LOSS OF GLUTATHIONE PEROXIDASE 1 ATTENUATES COLITIS AND IS CRITICAL IN ACTIVATING EPITHELIAL REGENERATIVE RESPONSES
Authors: Hendren Jared , Kasnyik Koral , Williams Christopher , Short Sarah 
Published: January 2021

Abstract
Many selenium-containing “selenoproteins” function as antioxidants, and work by our lab and others has demonstrated that selenoproteins often protect against intestinal inflammatory diseases, including colitis. Glutathione peroxidase 1 (GPx1) is a ubiquitous, mitochondrial and cytosolic selenoprotein which catalyzes the reduction of hydrogen peroxide by glutathione. Previously, we determined that despite its antioxidant role, loss of GPx1 greatly reduced disease severity in the dextran sodium sulfate (DSS) colitis model. Furthermore, GPx1 loss increased baseline intestinal cell proliferation, enhanced enteroid plating efficiency, and induced expression of stem cell-associated genes, such as Lgr5.
Next, we aimed to determine the mechanism by which GPx1 modifies response to DSS. We observed that GPx1 is increased in colonic tissues from DSS-treated mice as compared to nontreated controls, suggesting that GPx1 may functionally contribute to intestinal injury responses. While GPx1 is expressed in both intestinal epithelial and immune cells, in situ hybridization to visualize Gpx1 identified epithelial cells as the most highly expressing cell type, with the greatest Gpx1 upregulation observed in wound-adjacent and regenerative crypts. Next, we investigated whether GPx1 loss affects stem cell function after injury. Here, we determined that both proliferation (p&lt;0.01) and Lgr5 expression (p&lt;0.05) were increased in the crypts of Gpx1-/- DSS-treated mice in comparison to WT controls. Similarly, organoids established from ulcerative colitis tissue displayed increased growth rates (p&lt;0.01), expression of stem cell and Wnt target genes such as AXIN2 (p&lt;0.0001) and LGR5 (p&lt;0.01), and proliferation (p&lt;0.05) following GPX1 knockdown. Together, these results indicate that GPx1 has an epithelial-cell autonomous role, and that its loss activates stem cell and proliferative responses which may both protect from intestinal injury and promote healing.
Interestingly, recent research has highlighted the role of cellular metabolism in maintaining intestinal stem cell function, and GPx1 has previously been implicated in these processes. RNA-sequencing from DSS-treated mice and gene set enrichment analysis identified a positive association with oxidative phosphorylation-associated genes in Gpx1-/- mice (NES: 1.78; FDR q-val: 0.01), suggesting altered metabolism which may favor stem cell function. Further analysis of cellular metabolism using GPX1 knockdown colorectal cancer cells observed higher basal respiration (p&lt;0.0001) and ATP generation (p&lt;0.0001). Together, these results suggest that unlike other intestinal selenoproteins studied to date, loss of GPx1 augments stem cell injury responses to protect against intestinal inflammation, likely via augmenting epithelial regenerative responses.