Machine learning approaches to predicting medication nonadherence: a scoping review.

Background: Medication nonadherence is a common, preventable cause of adverse clinical outcomes. Predictive models identifying risk of nonadherence could enable proactive intervention.

Objective: This scoping review aimed to describe relevant predictors, model training and evaluation processes, and how adherence was classified to inform implementation of clinically actionable models.

Impact of Precision-Guided Dosing on Clinical Decision-Making and Health Care Utilization in Inflammatory Bowel Disease: A Retrospective Pretest/Posttest Real-World Study.

Background: Precision-guided dosing (PGD) is a personalized tool that optimizes clinical decision-making in the treatment of inflammatory bowel disease (IBD) with infliximab (IFX) and its biosimilars. PGD employs nonlinear mixed-effect models using patient-specific pharmacokinetic parameters to predict infliximab trough concentrations without the need to wait until the actual trough measurement. This approach calculates patient-specific clearance (CL) and provides tailored IFX dosing and administration intervals aimed at achieving target trough levels.

Phosphatidylinositol 3-Kinase Signaling Enhances Intestinal Crypt Epithelial Cell Recovery after Radiation.

Intestinal stem cell (ISC) signaling maintains the balance of self-renewal and differentiation. Herein, the role of phosphatidylinositol 3-kinase (PI3K) signaling in ISC responses to radiation was interrogated using Villin-Cre pik3r1 (p85) mice and p85α-deficient human enteroids (shp85α). Lethal whole-body irradiation in mice was performed to monitor PI3K-mediated survival responses.

The Clinical Utility of Precision-Guided Dosing for Adalimumab Therapy Optimization in Inflammatory Bowel Disease: A Clinical Experience Program.

: This study aimed to establish the clinical utility of a therapeutic drug monitoring (TDM)-supported, model-informed precision dosing (MIPD) approach (precision-guided dosing [PGD]) by assessing the impact of pharmacokinetic (clearance [CL]) and clinical laboratory parameters on adalimumab (ADA) dosage adjustments during maintenance therapy for inflammatory bowel disease (IBD). : In the EMPOWER study, blood was collected at any time post-ADA injection. Pharmacokinetic (PK) testing was conducted in an accredited lab.

Dual Biologic Therapy Induces Remission in Refractory Crohn's Disease With Vedolizumab and Ustekinumab.

Background: Despite advancements in the therapeutic armamentarium for Crohn's disease (CD), biologic and small molecule monotherapies are associated with sub-optimal response and remission rates. Utilizing dual biologic therapy (DBT) holds the potential to increase efficacy in the treatment of refractory or partially responsive CD. Evidence pertaining to this strategy remains limited.

Applying Machine Learning Models Derived From Administrative Claims Data to Predict Medication Nonadherence in Patients Self-Administering Biologic Medications for Inflammatory Bowel Disease.

Background: Adherence to self-administered biologic therapies is important to induce remission and prevent adverse clinical outcomes in Inflammatory bowel disease (IBD). This study aimed to use administrative claims data and machine learning methods to predict nonadherence in an academic medical center test population.

Methods: A model-training dataset of beneficiaries with IBD and the first unique dispense of a self-administered biologic between June 30, 2016 and June 30, 2019 was extracted from the Commercial Claims and Encounters and Medicare Supplemental Administrative Claims Database.

Mitochondrial function and gastrointestinal diseases.

Mitochondria are dynamic organelles that function in cellular energy metabolism, intracellular and extracellular signalling, cellular fate and stress responses. Mitochondria of the intestinal epithelium, the cellular interface between self and enteric microbiota, have emerged as crucial in intestinal health. Mitochondrial dysfunction occurs in gastrointestinal diseases, including inflammatory bowel diseases and colorectal cancer.

Effectiveness of Upadacitinib for Patients With Acute Severe Ulcerative Colitis: A Multicenter Experience.

Introduction: A significant proportion of patients with acute severe ulcerative colitis (ASUC) require colectomy.

Methods: Patients with ASUC treated with upadacitinib and intravenous corticosteroids at 5 hospitals are presented. The primary outcome was 90-day colectomy rate.

Modulating microbiome-immune axis in the deployment-related chronic diseases of Veterans: report of an expert meeting.

The present report summarizes the United States Department of Veterans Affairs (VA) field-based meeting titled "Modulating microbiome-immune axis in the deployment-related chronic diseases of Veterans." Our Veteran patient population experiences a high incidence of service-related chronic physical and mental health problems, such as infection, irritable bowel syndrome (IBS), inflammatory bowel disease (IBD), various forms of hematological and non-hematological malignancies, neurologic conditions, end-stage organ failure, requiring transplantation, and posttraumatic stress disorder (PTSD). We report the views of a group of scientists who focus on the current state of scientific knowledge elucidating the mechanisms underlying the aforementioned disorders, novel therapeutic targets, and development of new approaches for clinical intervention.

Study Transportation of Drugs within Newly Established Murine Colon Organoid Systems.

The development of 3D organoids of the small intestine is a tremendous breakthrough in drug development and biological research. However, the development of colonic organoids (i.e.

Inflammatory Bowel Disease in Appalachian Kentucky: An Investigation of Outcomes and Health Care Utilization.

Background: Rural residence has been associated with a lower incidence of inflammatory bowel disease (IBD) but higher health care utilization and worse outcomes. Socioeconomic status is intrinsically tied to both IBD incidence and outcomes. Inflammatory bowel disease outcomes have not been investigated in Appalachia: a rural, economically distressed region rife with risk factors for both increased incidence and unfavorable outcomes.

Chronic opioid use is associated with early biologic discontinuation in inflammatory bowel disease.

Background: Chronic opioid use is associated with poorer clinical outcomes in inflammatory bowel disease.

Aims: To investigate an association between chronic opioid use and persistence with biologic agents in management of inflammatory bowel disease.

Methods: A total of 16 624 patients diagnosed with inflammatory bowel disease and receiving a first-time biologic prescription from 2011 to 2016 were identified retrospectively from the Truven MarketScan Database.

Ustekinumab dose escalation improves clinical responses in refractory Crohn's disease.

Background: Clinicians often utilize off-label dose escalation of ustekinumab (UST) in Crohn's disease (CD) patients with disease refractory to standard dosing. Previous studies report mixed results with dose escalation of UST.

Methods: A retrospective observational study of 143 adult patients with CD receiving UST over a 33-month time period was conducted.

Vedolizumab Dose Escalation Improves Therapeutic Response in a Subset of Patients with Ulcerative Colitis.

Background: The Gemini trial failed to detect a significant difference in response rate for patients with ulcerative colitis (UC) randomized to standard (every 8 week) vedolizumab dosing vs escalated (every 4 week) dosing. Subsequent real-world data imply the Gemini trial design may have obscured a benefit of escalated dosing.

Aims: We investigated outcomes after vedolizumab dose escalation for patients with UC.

Doublecortin-like kinase 1 promotes hepatocyte clonogenicity and oncogenic programming via non-canonical β-catenin-dependent mechanism.

Chronic liver injury is a risk factor for cirrhosis and hepatocellular carcinoma (HCC). The molecular mechanisms that regulate the decision between normal injury repair and neoplastic initiation are unclear. Doublecortin-like kinase 1 (DCLK1), a tumor stem cell marker, is induced during cirrhosis and HCC.

Double Biologic Therapy for Refractory Stricturing Crohn's Disease: A Successful Case of Deep Remission with Ustekinumab and Vedolizumab.

Stricturing Crohn's disease (CD) is a severe phenotype that presents unique challenges to therapeutic management. Emerging literature suggests that anti-TNF monoclonal antibody (mAb) therapies are inadequate for preventing progression to stricture. We hereby present a case of a patient with refractory CD who required multiple surgical resections despite several anti-TNF treatment regimens.

SIRT2 Contributes to the Regulation of Intestinal Cell Proliferation and Differentiation.

Background And Aims: Intestinal mucosa undergoes a continual process of proliferation, differentiation, and apoptosis. Disruption of this homeostasis is associated with disorders such as inflammatory bowel disease (IBD). We investigated the role of Sirtuin 2 (SIRT2), a NAD-dependent protein deacetylase, in intestinal epithelial cell (IEC) proliferation and differentiation and the mechanism by which SIRT2 contributes to maintenance of intestinal cell homeostasis.

Vitamin C and B as new biomaterials to alter intestinal stem cells.

Vitamin C (ascorbic acid) and vitamin B (niacin) have been extensively studied since the 20th century. In the area of stem cell biology, vitamin C has shown its direct impact toward homeostasis and epigenetic changes (D'Aniello et al., Stem Cells International, 2017, 1-16).

The mitochondrial retrograde signaling regulates Wnt signaling to promote tumorigenesis in colon cancer.

Cancer cells are known to upregulate aerobic glycolysis to promote growth, proliferation, and survival. However, the role of mitochondrial respiration in tumorigenesis remains elusive. Here we report that inhibition of mitochondrial function by silencing TFAM, a key transcription factor essential for mitochondrial DNA (mtDNA) replication and the transcription of mtDNA-encoded genes, markedly reduced tumor-initiating potential of colon cancer cells.

Correction: Validation of near infrared fluorescence (NIRF) probes in vivo with dual laser NIRF endoscope.

[This corrects the article DOI: 10.1371/journal.pone.

Blocking NF-κB Activation in Ly6c Monocytes Attenuates Necrotizing Enterocolitis.

Necrotizing enterocolitis (NEC) is a devastating disease affecting premature infants with intestinal inflammation and necrosis. The neonatal intestinal inflammatory response is rich in macrophages, and blood monocyte count is low in human NEC. We previously found that NF-κB mediates the intestinal injury in experimental NEC.