bluuebunny/crossref_metadata_2025_split huggingface dataset:
Quantifying rupture characteristics of microearthquakes in the Parkfield Area using a high-resolution borehole network
Authors: Pennington Colin N , Wu Qimin , Chen Xiaowei , Abercrombie Rachel E 
Published: January 2023

SUMMARYIt is well known that large earthquakes often exhibit significant rupture complexity such as well separated subevents. With improved recording and data processing techniques, small earthquakes have been found to exhibit rupture complexity as well. Studying these small earthquakes offers the opportunity to better understand the possible causes of rupture complexities. Specifically, if they are random or are related to fault properties. We examine microearthquakes (M &lt; 3) in the Parkfield, California, area that are recorded by a high-resolution borehole network. We quantify earthquake complexity by the deviation of source time functions and source spectra from simple circular (omega-square) source models. We establish thresholds to declare complexity, and find that it can be detected in earthquakes larger than magnitude 2, with the best resolution above M2.5. Comparison between the two approaches reveals good agreement (&gt;90 per cent), implying both methods are characterizing the same source complexity. For the two methods, 60–80 per cent (M 2.6–3) of the resolved events are complex depending on the method. The complex events we observe tend to cluster in areas of previously identified structural complexity; a larger fraction of the earthquakes exhibit complexity in the days following the Mw 6 2004 Parkfield earthquake. Ignoring the complexity of these small events can introduce artefacts or add uncertainty to stress drop measurements. Focusing only on simple events however could lead to systematic bias, scaling artefacts and the lack of measurements of stress in structurally complex regions.
THE USE OF IMMUNOMODULATORS, BIOLOGIC THERAPIES AND SMALL MOLECULES IN PATIENTS WITH INFLAMMATORY BOWEL DISEASE AND SOLID ORGAN TRANSPLANTS
Authors: Ghusn Wissam , Francis Fadi , Farraye Francis , Hashash Jana G 
Published: January 2023

Abstract

INTRODUCTION
Over the past 20 years, the number of solid organ transplants (SOT) for a variety of indications has been on the rise. Consequently, more patients with inflammatory bowel diseases (IBD) are also receiving SOT. Although SOT related immunosuppression may at times control IBD related inflammation, many patients still require additional immunosuppressive medications for control of their IBD. With the growing therapeutic armamentarium for IBD, physicians are in search for guidance on the safety of using additional immunosuppressive medications in patients who are already receiving transplant related immunosuppressive medications.

METHODS
We performed a review of published literature that addressed the use of immunomodulators, biologic agents, and small molecules in patients with IBD who also had a SOT. We searched PubMed, Scopus, MEDLINE, and Google Scholar databases for studies published on the topic in English between January 1st, 1910, and August 1st, 2022. We have included data from systematic reviews, meta-analyses, case reports and case series to assess the safety, effectiveness, and side effects of immunomodulators, biologic therapies and small molecules in patients with liver, renal and/or heart transplantations.

RESULTS
We identified 25 publications on liver transplants, 6 on renal transplants, and 1 on heart transplants in patients with IBD. Among liver transplant patients, the most common immunosuppressive medications used were tacrolimus, mycophenolate mofetil, cyclosporine and steroids. In patients with IBD, anti-TNF agents (infliximab and adalimumab) were used in SOT with no major adverse safety concerns. The most common adverse events included infections (Clostridioides difficile and CMV) and malignancies (colon cancer). As for anti-integrin agents (vedolizumab and natalizumab) and ustekinumab, their efficacy and safety were mainly reported in patients with liver transplant on tacrolimus with no major adverse events reported. For patients with renal transplant, the main immunosuppression used were cyclosporine and tacrolimus. The combination of these immunosuppressive drugs with either anti-TNF therapy or ustekinumab had a good safety profile with rare malignancy occurrence. In one case report with heart transplant in a patient with IBD and on tacrolimus, no complications were reported.

CONCLUSION
SOT has become the mainstay for treating several common diseases. As such, gastroenterologists will care for more patients with IBD who have had a SOT. From this extensive review, the use of anti-TNF, anti-integrin agents and ustekinumab seem to be safe in patients with SOT, regardless of their transplant related immunosuppression which is usually comprised of tacrolimus, cyclosporine, and prednisone. More studies are needed in patients with renal and heart transplant and in patients treated with small molecules for their IBD.
A NOVEL GUT-RESTRICTED ARYL HYDROCARBON RECEPTOR AGONIST WITH ACTIVITY IN THE DEXTRAN SODIUM SULFATE COLITIS MURINE MODEL
Authors: Davidson Matt , Saiki Julie 
Published: January 2023

Abstract

BACKGROUND
Patients with inflammatory bowel disease (ulcerative colitis, Crohn’s disease) have decreased production of endogenous aryl hydrocarbon receptor (AhR) ligands in colon tissue. Activation of the AhR is a potential novel therapeutic target for ulcerative colitis and may play an important role in promoting immune homeostasis through increased IL-22 production, downregulation of proinflammatory mediators, and improved epithelial barrier function. Indigo naturalis, a botanical extract containing potent AhR agonists, has been effective for the treatment of moderate-to-severe and treatment-refractory ulcerative colitis in multiple clinical studies. The most potent AhR agonist in indigo naturalis is indirubin.

OBJECTIVE
The objective was to develop novel indirubin prodrugs that maximize local colonic delivery and minimize systemic exposure to reduce the risk of potential systemic side effects.

RESULTS
We developed a novel synthetic small molecule prodrug of indirubin that maximizes colonic exposure and minimizes systemic exposure. In a dextran sodium sulfate (DSS)-induced colitis murine model, oral administration of our lead prodrug significantly reduced Disease Activity Index and weight loss similar in magnitude to indirubin. The prodrug resulted in colon concentrations of indirubin that were over 100-fold greater than plasma concentrations, and low systemic organ exposure.

CONCLUSION
Azora’s novel indirubin prodrug enhanced colonic delivery of indirubin while maintaining minimal systemic exposure in a DSS colitis murine model and may reduce the risk of systemic side effects. This compound may be suitable for development as a first-in-class oral AhR agonist for the treatment of ulcerative colitis.
EFFICACY AND SAFETY OF VEDOLIZUMAB AND TUMOR NECROSIS FACTOR INHIBITORS IN THE TREATMENT OF STEROID-REFRACTORY MICROSCOPIC COLITIS: A SYSTEMATIC REVIEW AND META-ANALYSIS
Authors: Chehade Nabil El Hage , Shah Sagar , Pardi Darrell , Farraye Francis , Al Hashash Jana 
Published: January 2023

Abstract

BACKGROUND
Tumor necrosis factor (TNF-α) inhibitors and the α4β7 integrin antagonist, vedolizumab have been investigated as a treatment option for patients with steroid-refractory microscopic colitis (MC) with controversial findings.

AIMS
To perform a systematic review and meta-analysis to evaluate the benefit of vedolizumab and TNF-α inhibitors in patients with steroid-refractory MC.

METHODS
Retrospective cohort studies and case series involving adult patients with steroid-refractory MC who either received vedolizumab, adalimumab, or infliximab were eligible for inclusion. Outcomes of interest included the rate of clinical remission at induction, clinical response, maintenance of remission, histologic remission, and overall medication related adverse effects. Pooled proportional meta-analyses were used to calculate the overall rates of the primary and secondary endpoints. Heterogeneity was assessed using the I2 statistic. Publication bias was assessed via visual inspection of the funnel plots and using Egger’s regression. All statistical analysis was performed in R using the metafor and meta packages.

RESULTS
A total of 14 retrospective case series/studies involving 164 patients were included. Pooled analysis showed a clinical remission rate of 63.5% (95% CI [0.483; 0.776], I2=43% P=0.08), 57.8% (95% CI [0.3895; 0.7571], I2=0%, P=0.7541), and 39.3% (95% CI [0.0814; 0.7492, I2=66%, P=0.02) for vedolizumab, infliximab, and adalimumab, respectively. The maintenance of remission rate was 60.5% (95% CI [0.2772; 0.8953], I2=67%, P=0.03), 45.3% (95% CI [0.1479; 0.7747], I2=0%, P=0.36) and 32.5% (95% CI [0.000; 0.8508], I2=53%, P=0.14) in patients who received vedolizumab, infliximab, and adalimumab, respectively. Rate of biologic-related adverse events warranting discontinuation of therapy was 12.2%, 32.9%, and 23.0% for the vedolizumab, infliximab, and adalimumab groups, respectively.

CONCLUSION
Vedolizumab and anti-TNF-α agents demonstrated a clinical benefit in the treatment of steroid-refractory MC and with a tolerable safety profile. Given the nature of included studies, superiority of either therapy could not be elucidated. Future randomized controlled trials are needed to standardize study protocols, compare vedolizumab with TNF-α inhibitors, and further examine data on patients’ quality of life.

Forest plot showing the pooled clinical remission rate at induction in patients with steroid-refractory microscopic colitis receiving (A) vedolizumab or TNF inhibitors (B)

Data summary of the meta-analyses of the studies investigating secondary endpoints in patients with refractory MC receiving either (A) vedolizumab or (B) TNF inhibitors

ABBREVIATIONS
MR, maintenance remission; CR, clinical response; HR, histologic remission; OAE, overall adverse effects.
LONG RECTAL CUFF SYNDROME AFTER ILEOANAL POUCH FOR INFLAMMATORY BOWEL DISEASE
Authors: Maspero Marianna , Liska David , Kessler Hermann , Lipman Jeremy , Steele Scott , Hull Tracy , Qazi Taha , Rieder Florian , Cohen Benjamin , Holubar Stefan 
Published: January 2023

Abstract

BACKGROUND
Restorative proctocolectomy with ileal pouch anal anastomosis (IPAA) removes the entire rectum to the anal canal, but is technically challenging, especially with minimally invasive (MIS) approaches. Pouches are most commonly double-stapled, leaving a 1-2 cm “rectal cuff”. If the cuff is longer, patients may develop recurrent ulcerative proctitis (UP) or rectal stricture (RS) of the retained rectum. The aim of this study is to describe long rectal cuff syndrome (LRCS) and its outcomes after redo IPAA performed for long rectal cuffs.

METHODS
We defined LRCS as a constellation of UP or RS symptoms related to a long (≥ 4 cm) rectal cuff. We retrospectively reviewed our prospectively maintained Pouch Registry to identify patients whose indication for redo pouch was LRCS. We report their presentation and outcomes after redo IPAA for LRCS. Figures are frequency (percentage) and median (interquartile range).

RESULTS
LRCS was the primary indication for redo IPAA in 40 patients (7% of the redo IPAA cases at our Center); median age at redo surgery, 42.5 (29 – 49 years); 18 (42%) were females; 36 (90%) patients were referral cases. Diagnosis at index IPAA was ulcerative colitis in 39 (97.5%), and Crohn’s in 1 (2.5%) case. The index pouch was performed MIS in 14 (35%). The median rectal cuff length was 6 (5 – 8) cm, with 13 (32.5%) patients having a cuff ≥ 8 cm.
After a median of 21 (16 – 68) months, patients most commonly presented (31, 77.5%) with UP-symptoms (urge-incontinence, frequency, abdominopelvic or rectal pain) or with obstructive (9, 22.5%) symptoms (crampy abdominopelvic pain, outlet obstruction). Preoperative pouchoscopy was available in 32 (80%) cases: pouchoscopy findings included proctitis (18, 56%), rectal stricture (16, 50%), and/or dilated pouch (7, 22%). The median interval between the index pouch and redo pouch was 31 months (16 – 67.5). The pouch was disconnected and re-anastomosed to anus in 16 (40%), while excised with neo-pouch construction in 24 (60%) of cases. The anastomosis was stapled vs. handsewn 25 (62.5%) vs. 15 (27.5%). Pathologic exam revealed chronic active proctitis in 38 (90%) cases; the remained showed other pathologic changes.
In terms of long-term outcomes, two (5%) patients never had their stoma closed after redo due to Crohn’s-related pouch complication, and fistulae development, respectively. After a median follow up of 34.5 (12 – 109) months, pouch failure occurred in 9 (22.5%) cases. The median interval between redo IPAA and pouch failure was 10 (4 – 34) months. Pouch survival at 3-, 5- and 10-years was 78%, 72%, and 63%.

CONCLUSION
Long rectal cuff syndrome is a potentially avoidable complication which presents with symptoms from either ulcerative proctitis or stricture. Redo IPAA can be offered as treatment to maintain intestinal continuity and may allow long-term pouch salvage in many cases.
THE IMPACT OF INFLAMMATORY BOWEL DISEASES ON THE OUTCOMES OF PATIENTS ADMITTED WITH ACUTE VIRAL HEPATITIS: A 2016-2019 NATIONWIDE ANALYSIS
Authors: Kilani Yassine , Arshad Iqra , Aldiabat Mohammad , Kamal Syeda Ashna Fatima , Favour Markson , Sohail Haris 
Published: January 2023

Abstract

INTRODUCTION
Inflammatory bowel diseases (IBD) are thought to be caused by a dysregulated immune response in the digestive tract, amongst other factors (environmental, genetic predisposition, microbiota). Data on acute viral hepatitis (AVH) infection outcomes in patients with underlying IBD are scarce. We aimed to investigate the relationship between IBD and outcomes of patients with AVH.

METHODS
This is a retrospective longitudinal study of patients admitted with a primary diagnosis of AVH (A,B,C,D,E). We retrieved data from the Nationwide Inpatient Sample (NIS) databases from the years 2016 to 2019 using ICD-10 CM codes for AVH. Multivariate logistic regression analysis was performed in patients with IBD to estimate the effect of IBD on the primary outcomes of mortality, hospital utilization, and acute hepatitis complications, adjusted for patient and hospital confounders. A T-Test and Chi Square test were performed to compare baseline characteristics in patients admitted for AVH with and without a secondary diagnosis of IBD. We used STATA® Version 17.0 Software (STATACORP, TEXAS, USA) for analysis. The p-value was set at p &lt; 0.05 for statistical significance.

RESULTS
A total of 47614 adult patients with a primary diagnosis of AVH were identified; four hundred twenty five (0.9%) had a secondary diagnosis of IBD. Most were middle-aged (mean age: 44 years), male (53%) white (78%), and were admitted in large sized (51%) and teaching hospitals (68%). There was no statistically significant change in the length of stay or total healthcare cost associated with the presence of IBD. Having IBD was associated with no change in the risk of fulminant hepatitis (OR = 0.55, p= 0.262, CI: 0.19 - 0.55), hypoglycemia (OR = 1.14, p= 0.904, CI: 0.13 - 9.56), thrombocytopenia (OR = 0.46, p= 0.209, CI: 0.14 - 1.53), and coagulopathy (OR = 1.22, p= 0.781, CI: 0.29 - 5.12). No case of mortality, hepatorenal syndrome or liver transplant was reported.

DISCUSSION
Despite the fact that IBD is associated with a dysregulated immune response in the digestive tract, our study showed that the presence of IBD in patients affected by acute viral hepatitis does not carry a significant impact on the outcomes of IBD (hospital utilization, morbidity, mortality). Broader studies are required to establish an association between IBD and AVH outcomes.
REAL-WORLD USTEKINUMAB PERSISTENCE IN PATIENTS WITH ULCERATIVE COLITIS ATTAINING THE MAINTENANCE PHASE
Authors: Zhdanava Maryia , Kachroo Sumesh , Shah Aditi , Ding Zhijie , Holiday Christopher , Lefebvre Patrick , Zhao Ruizhi , Kerner Caroline , Pilon Dominic 
Published: January 2023

Abstract

BACKGROUND
Sustained use of biologics and small molecule/advanced therapy has proven to be effective for controlling disease activity in ulcerative colitis (UC). The anti-interleukin agent ustekinumab was recently approved for UC in 2019. This study aimed to describe real-world ustekinumab persistence among patients with UC attaining the maintenance phase.

METHODS
Adults with UC selected from the Komodo Health’s comprehensive dataset had the first claim for ustekinumab (index date) between 10/21/2019 and 08/13/2021. Patients had ≥12 months of continuous insurance eligibility pre-index (baseline period), ≥1 claim with a diagnosis of UC at baseline or on the index date and persisted to their first subcutaneous ustekinumab claim (maintenance phase). Patients with diagnoses for other immune disorders at baseline or diagnoses for Crohn’s disease at any time were excluded. Persistence to ustekinumab was defined as absence of a therapy exposure gap of &gt;120 days between days of supply or end of follow-up. Composite endpoints were persistence while being corticosteroid-free (no corticosteroids with ≥14 days of supply after day 90 post-index), and persistence while on monotherapy (no immunomodulators/non-index biologics or advanced therapies). Persistence endpoints were described post-maintenance phase until the earlier of 12 months, end of insurance eligibility, or data. Kaplan-Meier curves were used to assess persistence outcomes in all patients and among patients without prior biologic/advanced therapy exposure pre-index (bio-naïve).

RESULTS
778 patients attaining the ustekinumab maintenance phase were selected, 236 (30.3%) were bio-naïve (Fig. 1). Mean follow-up time post-index was 13.5 months overall and 12.7 months for bio-naïve patients. By 12 months post-maintenance, 73.2% of all patients and 75.5% of bio-naïve patients were persistent to ustekinumab (Fig. 2). Additionally, amongst patients who were persistent and corticosteroid-free between the index date and the start of maintenance phase, 47.0% of all patients and 55.1% of bio-naïve patients remained persistent and corticosteroid-free 12 months after their first maintenance claim. Further, among patients who were persistent on monotherapy at the start of maintenance phase, 63.6% of all patients and 68.1% of bio-naïve patients remained persistent on monotherapy at 12 months.

CONCLUSIONS
In this study, 12 months after their first ustekinumab maintenance claim for UC, most patients who attained the maintenance phase were persistent to treatment, around half of patients who were also corticosteroid-free at the start of the maintenance phase remained persistent and corticosteroid-free, and most patients who were persistent on monotherapy at the start of the maintenance phase remained persistent on monotherapy.
FUNCTIONAL DISABILITY INVENTORY AND ASSOCIATIONS WITH RACE, ETHNICITY, INCOME AND FOOD INSECURITY
Authors: Zeky Nicole , LeBlanc Colleen , McDonough Elizabeth , Moulton Dedrick 
Published: January 2023

Abstract

PURPOSE
Inflammatory bowel disease (IBD) is an autoimmune disease that consists of Crohn’s Disease (CD) and ulcerative colitis (UC). Food insecurity is defined as limited or uncertain access to enough food. It is estimated that 1 in 7 children in the United States experience food insecurity or about 13 million children. Louisiana has one of the higher rates of food insecurity in the country with over 249,000 children affected. Food insecurity has been associated with worse health outcomes in children including developmental risks, poor mental health, and poor educational outcomes. Functional Disability Inventory (FDI) is a measure of limitations in both physical and psychosocial functioning secondary to physical health. Our hypothesis is that patients in food insecure homes will have higher FDI scores compared to those in food secure homes.

METHODS
This study is a prospective study of newly diagnosed IBD patients seen by the Division of Pediatric Gastroenterology at Children’s Hospital of New Orleans. Patients were screened for food insecurity using the United States Department of Agriculture’s food insecurity screening questionnaire and the American Academy of Pediatrics’ Food Insecurity 2-Question Screen. Disability scores were obtained at diagnosis using the FDI self-reporting questionnaire if older than 12 years of age or a parent form was completed for patients less than 12.

RESULTS
Our study consisted of 20 newly diagnosed pediatric IBD patients with an average age of 14.5 years. Nineteen (95%) patients had CD. Most patients were female (70%), non-Hispanic white (50%) with Medicaid (55%) as their primary insurance. Eight (40%) patients were African American and two (10%) were listed as other. Eight patients or their caregivers identified as living in a food insecure home (40%) and these patients averaged a FDI score of 10.2 The food secure group had an average FDI of 9.3. Non-Hispanic, white patients had an average FDI score of 10.5 while the minority patients had an average FDI of 8.5. Only two patients lived in an area with a median household income below poverty with an average FDI of 15.5. Ten patients lived below the state median income and had an average FDI was 8.2. Those patients living in areas above the state median income level, 8 total, had the highest FDI scores, 10.8.

CONCLUSION
Food insecurity had higher rates of disability scores compared to families from food secure homes. Families in higher income areas and who were non-Hispanic white had higher FDI scores compared to minority patients and those in lower income areas. Further data will be collected with changes in FDI through the first 6 months of diagnosis. Additional larger studies are needed to determine a relationship between FDI scores and food insecurity in pediatric IBD.