Memory-like differentiation enhances NK cell responses against colorectal cancer.

Metastatic (m) colorectal cancer (CRC) is an incurable disease with a poor prognosis and thus remains an unmet clinical need. Immune checkpoint blockade (ICB)-based immunotherapy is effective for mismatch repair-deficient (dMMR)/microsatellite instability-high (MSI-H) mCRC patients, but it does not benefit the majority of mCRC patients. NK cells are innate lymphoid cells with potent effector responses against a variety of tumor cells but are frequently dysfunctional in cancer patients.

NAFLD Is Associated With Quiescent Rather Than Active Crohn's Disease.

Background And Aims: Crohn's disease (CD) confers an increased risk of nonalcoholic fatty liver disease (NAFLD), but the pathogenesis remains poorly understood. We determined if active intestinal inflammation increases the risk of NAFLD in patients with CD.

Methods: Two cohorts (2017/2018 and 2020) with CD and no known liver disease were enrolled consecutively during staging magnetic resonance enterography.

Nonalcoholic Fatty Liver Disease Is a Risk Factor for Thiopurine Hepatotoxicity in Crohn's Disease.

Background: Patients with Crohn's disease (CD) are predisposed to nonalcoholic fatty liver disease (NAFLD). CD management often includes thiopurines which can promote hepatotoxicity. We aimed to identify the role of NAFLD on the risk of developing liver injury from thiopurines in CD.

Healthcare Disparities Among Homeless Patients Hospitalized With Gastrointestinal Bleeding: A Propensity-Matched, State-Level Analysis.

Goals: Examine outcomes among homeless patients admitted with gastrointestinal (GI) bleeding, including all-cause mortality and endoscopic intervention rates.

Background: Hospitalizations among homeless individuals have increased steadily since at least 2007 but little is known about GI outcomes in these patients.

Study: The 2010-2014 Healthcare Utilization Project (HCUP) State Inpatient Databases from New York and Florida were used to identify adults admitted with a primary diagnosis of acute upper or lower GI bleed.

Inflammatory Bowel Disease Is Associated With an Increased Risk of Incident Acute Arterial Events: Analysis of the United Kingdom Biobank.

Background & Aims: Population-based studies have suggested an increased risk of acute arterial events (AAEs) in patients with inflammatory bowel disease (IBD). We aimed to assess the risk of incident AAEs and premature AAEs, adjusted for diet, physical activity, and inflammation biomarkers, in participants with IBD in the UK Biobank (UKB) METHODS: UKB participants with IBD and without prevalent AAEs at enrollment were matched to random non-IBD controls. A Cox regression model, adjusting for baseline cardiovascular and IBD risk factors, diet, physical activity, and high-sensitivity C-reactive protein, estimated adjusted hazard ratios (aHRs) for association between IBD and AAEs or premature AAEs (age, <55 years for men and <65 years for women).

Systematic Review With Meta-analysis: Safety and Effectiveness of Combining Biologics and Small Molecules in Inflammatory Bowel Disease.

Background: Combining biologics and small molecules could potentially overcome the plateau of drug efficacy in inflammatory bowel disease (IBD). We conducted a systematic review and meta-analysis to assess the safety and effectiveness of dual biologic therapy (DBT), or small molecule combined with a biologic therapy (SBT) in IBD patients.

Methods: We searched MEDLINE, EMBASE, Scopus, Web of Science, Cochrane Database of Systematic Reviews, and Clinical trials.

The Impact of Night-time Emergency Department Presentation on Upper Gastrointestinal Hemorrhage Outcomes.

Goals: The aim was to investigate the impact of night-time emergency department (ED) presentation on outcomes of patients admitted for acute upper gastrointestinal hemorrhage (UGIH).

Background: The relationship between time of ED presentation and outcomes of gastrointestinal hemorrhage is unclear.

Study: Using the 2016 and 2017 Florida State Inpatient Databases which provide times of ED arrival, we identified and categorized adults hospitalized for UGIH to daytime (07:00 to 18:59 h) and night-time (19:00 to 06:59 h) based on the time of ED presentation.

STEMI associated with SARS-CoV-2 infection and the use of ECMO as a potential therapeutic approach in addition to the PCI.

A 55-year-old male presented to the emergency department with the complaints of chest pain that started 4 h before presentation. Pain was located over the anterior chest, 5 out of 10 intensity, with radiation to the left arm. Chest x-ray on admission showed severe diffuse bilateral pulmonary infiltrates concerning for COVID-19 pneumonia.

Predictors, rates, and trends of opioid use disorder among patients hospitalized with chronic pancreatitis.

Background: Patients with chronic pancreatitis (CP) suffer from pain and receive increased opioid prescriptions with a high risk of opioid use disorder (OUD). We studied the predictors, trends and outcomes of OUD among patients hospitalized with CP.

Methods: Records with CP (with/without OUD) were extracted from the Nationwide Inpatient Sample (NIS) 2012-2014, and the association of OUD with the burden of CP was calculated.

Real-World Effectiveness and Safety of Tofacitinib in Crohn's Disease and IBD-U: A Multicenter Study From the TROPIC Consortium.

The safety and efficacy of tofacitinib in Crohn's disease (CD) has been studied in 2 phase II trials in patients with moderate-to-severe CD with no new safety signals observed, but no significant difference from placebo in the primary efficacy endpoint of clinical response. However, post hoc analyses and smaller studies have observed clinical and biologic response to tofacitinib in patients with CD. There is a paucity of real-world effectiveness and safety data for tofacitinib in non-Food and Drug Administration label usage in patients with CD and patients with inflammatory bowel disease-unclassified (IBD-U).

Safety of Tofacitinib in a Real-World Cohort of Patients With Ulcerative Colitis.

Background & Aims: Adverse events (AEs) including reactivation of herpes zoster (HZ) and venous thromboembolism (VTE) have been reported from clinical trials of tofacitinib in ulcerative colitis (UC). We investigated the incidence rates of AEs in a real-world study of UC patients given tofacitinib.

Methods: We collected data from 260 patients with UC in the Tofacitinib Real-world Outcomes in Patients with ulceratIve colitis and Crohn's disease consortium study, performed at 6 medical centers in the United States.

Gender and Racial Differences in Hospitalizations for Primary Biliary Cholangitis in the USA.

Background/aim: The prevalence, characteristics, burden and trends of primary biliary cholangitis (PBC) hospitalizations in the USA remain unclear.

Method: We identified primary PBC hospitalizations from the National Inpatient Sample (NIS) 2007 through 2014 using ICD-9-CM codes. We calculated the rates and trends of hospitalization for PBC per 100,000 US population among each gender (males and females) and racial categories (Whites, Blacks, Hispanics and other racial minorities), and measured the predictors of hospitalization, and of mortality, charges and length of stay (LOS) among PBC hospitalizations.

Tumor Interferon Signaling Is Regulated by a lncRNA INCR1 Transcribed from the PD-L1 Locus.

Tumor interferon (IFN) signaling promotes PD-L1 expression to suppress T cell-mediated immunosurveillance. We identify the IFN-stimulated non-coding RNA 1 (INCR1) as a long noncoding RNA (lncRNA) transcribed from the PD-L1 locus and show that INCR1 controls IFNγ signaling in multiple tumor types. Silencing INCR1 decreases the expression of PD-L1, JAK2, and several other IFNγ-stimulated genes.

Glioblastoma infiltration of both tumor- and virus-antigen specific cytotoxic T cells correlates with experimental virotherapy responses.

The mode of action for oncolytic viruses (OVs) in cancer treatment is thought to depend on a direct initial cytotoxic effect against infected tumor cells and subsequent activation of immune cell responses directed against the neoplasm. To study both of these effects in a mouse model of glioblastoma (GBM), we employed murine GBM cells engineered to constitutively express the type I Herpes Simplex Virus (HSV1) HSV-1 receptor, nectin-1, to allow for more efficient infection and replication by oncolytic HSV (oHSV). These cells were further engineered with a surrogate tumor antigen to facilitate assays of T cell activity.

Predictors, burden and impact of cardiac arrhythmias among patients hospitalized with end-stage liver disease.

Background: Cirrhotic cardiomyopathy, hyperammonemia, and hepatorenal syndrome predispose to cardiac arrhythmias in End-stage liver disease (ESLD).

Objectives: Among ESLD hospitalizations, we evaluate the distribution and predictors of arrhythmias and their impact on hospitalization outcomes.

Methods: We selected ESLD records from the Nationwide Inpatient Sample (2007-2014), identified concomitant arrhythmias (tachyarrhythmias and bradyarrhythmias), and their demographic and comorbid characteristics, and estimated the effect of arrhythmia on outcomes (SAS 9.

Arming an Oncolytic Herpes Simplex Virus Type 1 with a Single-chain Fragment Variable Antibody against PD-1 for Experimental Glioblastoma Therapy.

Purpose: Glioblastoma (GBM) is resistant to standard of care. Immune checkpoints inhibitors (such as anti-PD-1 mAbs) efficiently restore antitumor T-cell activity. We engineered a new oncolytic herpes simplex virus (oHSV) expressing a single-chain antibody against PD-1 (scFvPD-1) to evaluate its efficacy in mouse models of GBM.

Immune evasion mediated by PD-L1 on glioblastoma-derived extracellular vesicles.

Binding of programmed death ligand-1 (PD-L1) to programmed cell death protein-1 (PD1) leads to cancer immune evasion via inhibition of T cell function. One of the defining characteristics of glioblastoma, a universally fatal brain cancer, is its profound local and systemic immunosuppression. Glioblastoma has also been shown to generate extracellular vesicles (EVs), which may play an important role in tumor progression.

Modeling tumor immunity of mouse glioblastoma by exhausted CD8 T cells.

T cell exhaustion occurs during chronic infection and cancers. Programmed cell death protein-1 (PD-1) is a major inhibitory checkpoint receptor involved in T cell exhaustion. Blocking antibodies (Abs) against PD-1 or its ligand, PD-L1, have been shown to reverse T cell exhaustion during chronic infection and cancers, leading to improved control of persistent antigen.

Novel Concepts for HIV Vaccine Vector Design.

The unprecedented challenges of developing effective vaccines against intracellular pathogens such as HIV, malaria, and tuberculosis have resulted in more rational approaches to vaccine development. Apart from the recent advances in the design and selection of improved epitopes and adjuvants, there are also ongoing efforts to optimize delivery platforms. Viral vectors are the best-characterized delivery tools because of their intrinsic adjuvant capability, unique cellular tropism, and ability to trigger robust adaptive immune responses.

Development of novel replication-defective lymphocytic choriomeningitis virus vectors expressing SIV antigens.

An important focus in vaccine research is the design of vaccine vectors with low seroprevalence and high immunogenicity. Replication-incompetent lymphocytic choriomeningitis virus (rLCMV) vectors do not elicit vector-neutralizing antibody responses, and homologous prime-boost regimens with rLCMV vectors induce boostable and protective T cell responses to model antigens in mice. However, cellular and humoral immune responses following homologous rLCMV vaccine regimens have not been rigorously evaluated in non-human primates (NHPs).