IL-23p19 Antagonists vs. Ustekinumab for Treatment of Crohn's Disease: A Meta-analysis of Randomized Controlled Trials.

Background And Aims: We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing interleukin (IL)-23p19 antagonists with ustekinumab, stratified by prior biologic exposure, in patients with moderate-to-severe Crohn's disease (CD).

Methods: Through a systematic review through August 17, 2024, we identified phase 2 and 3 RCTs comparing IL-23p19 antagonists vs. ustekinumab in adults with moderate-to-severe CD.

Keratorefractive Lenticule Extraction for Myopia and Myopic Astigmatism With the VISUMAX 800: 6-Month Outcomes of a Prospective Multi-center Post-market Clinical Follow-up Study.

Purpose: To report the outcomes of small incision lenticule extraction (SMILE) using the VISUMAX 800 laser (Carl Zeiss Meditec) in a post-market clinical follow-up study.

Methods: This was a prospective, non-randomized, multi-center, international, post-market clinical follow-up study. The study took place from July 2021 to March 2023 at five sites across Europe and Asia.

Tissue-resident memory CD8 T cell diversity is spatiotemporally imprinted.

Tissue-resident memory CD8 T (T) cells provide protection from infection at barrier sites. In the small intestine, T cells are found in at least two distinct subpopulations: one with higher expression of effector molecules and another with greater memory potential. However, the origins of this diversity remain unknown.

First-line pembrolizumab-axitinib versus sunitinib in metastatic RCC: subgroup analysis of patients enrolled in the phase 3 KEYNOTE-426 in Eastern Asia.

Background: The phase 3 open-label KEYNOTE-426 study demonstrated that first-line pembrolizumab plus axitinib improved overall survival (OS) and progression-free survival (PFS) versus sunitinib for metastatic renal cell carcinoma (mRCC) in a global population. This subgroup analysis investigated the efficacy and safety of pembrolizumab-axitinib versus sunitinib in patients enrolled in KEYNOTE-426 in East Asia (Japan, South Korea, and Taiwan).

Methods: Adults with clear cell mRCC were randomly assigned 1:1 to receive intravenous pembrolizumab 200 mg every 3 weeks with oral axitinib 5 mg twice daily or oral sunitinib 50 mg once daily (4 weeks on/2 weeks off).

Immune checkpoint inhibitor-induced severe epidermal necrolysis mediated by macrophage-derived CXCL10 and abated by TNF blockade.

Immune checkpoint inhibitors (ICI) represent new anticancer agents and have been used worldwide. However, ICI can potentially induce life-threatening severe cutaneous adverse reaction (SCAR), such as Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN), hindering continuous ICI therapy. We examine 6 cohorts including 25 ICI-induced SJS/TEN patients and conduct single-cell RNA sequencing (scRNA-seq) analysis, which shows overexpression of macrophage-derived CXCL10 that recruits CXCR3 cytotoxic T lymphocytes (CTL) in blister cells from ICI-SJS/TEN skin lesions.

Differential Efficacy of Advanced Therapies in Inducing Remission in Ulcerative Colitis Based on Prior Exposure to TNF Antagonists.

Background And Aims: We sought to ascertain how prior exposure to tumor necrosis factor (TNF) antagonists impacts treatment response with various classes of advanced therapies in patients with ulcerative colitis (UC), through a systematic review and meta-analysis.

Methods: Through a systematic review of multiple databases through June 30, 2024, we identified 17 randomized controlled trials in 8871 adults with moderate-severe UC who were treated with different advanced therapies vs placebo, and reported efficacy in induction of clinical remission, stratified by prior exposure to TNF antagonists. We calculated the ratio of odds ratio of achieving remission with active drug vs placebo, in TNF antagonist-naïve vs TNF antagonist-exposed patients.

Incidence of Adult Primary Immunoglobulin A Nephropathy among a Racially/Ethnically Diverse Population in the United States.

Introduction: IgA nephropathy (IgAN), a leading cause of kidney failure worldwide, is one of the most common forms of primary glomerulonephropathy with variability by race and ethnicity. Using a diverse cohort within a large integrated health system in the United States (US), we identified and characterized patients with biopsy-proven IgAN and report annual incidence rates across racial/ethnic groups and standardized to the US nationally.

Methods: A cross-sectional study between January 1, 2010, and December 31, 2021 within Kaiser Permanente Southern California was performed.

Analysis of genomic alternations in epidermal growth factor receptor (EGFR)-T790M-mutated non-small cell lung cancer (NSCLC) patients with acquired resistance to osimertinib therapy.

Background And Objectives: Genomic alterations after resistance to osimertinib therapy in advanced T790M-mutated non-small cell lung cancer (NSCLC) are complex and poorly understood. In this study, we aimed to detect these genomic alternations via comprehensive next-generation sequencing (NGS) of tissue and liquid biopsies.

Patients And Methods: From September 2020 to June 2021, 31 stage IIIB/IV T790M-mutated NSCLC patients who exhibited progressive disease after osimertinib therapy and provided written informed consent were recruited.

Long-term results of allogenic corneal lenticule of hyperopic SMILE for post-LASIK ectasia.

Post-laser-assisted keratomileusis (LASIK) corneal ectasia is a severe complication of corneal refractive surgery, and cryopreserved lenticules from hyperopic small incision lenticule extraction (SMILE) may offer a promising treatment though their long-term safety and efficacy are still under investigation. In this prospective case series, six eyes from six patients with post-LASIK ectasia received lenticules (mean cryopreserved time: 63 days). The procedure involved lifting the corneal flap, implanting the lenticule, and repositioning the flap.

Durvalumab after Chemoradiotherapy in Limited-Stage Small-Cell Lung Cancer.

Background: Adjuvant therapy with durvalumab, with or without tremelimumab, may have efficacy in patients with limited-stage small-cell lung cancer who do not have disease progression after standard concurrent platinum-based chemoradiotherapy.

Methods: In a phase 3, double-blind, randomized, placebo-controlled trial, we assigned patients to receive durvalumab at a dose of 1500 mg, durvalumab (1500 mg) plus tremelimumab at a dose of 75 mg (four doses only), or placebo every 4 weeks for up to 24 months. Randomization was stratified according to disease stage (I or II vs.

Evolution of Proton Radiation Therapy Brainstem Constraints on the Pediatric Proton/Photon Consortium Registry.

Purpose: Increasing concern that brainstem toxicity incidence after proton radiation therapy might be higher than with photons led to a 2014 University of Florida (UF) landmark paper identifying its risk factors and proposing more conservative dose constraints. We evaluated how practice patterns changed among the Pediatric Proton/Photon Consortium Registry (PPCR).

Material And Methods: This prospective multicenter cohort study gathered data from patients under the age of 22 years enrolled on the PPCR, treated between 2002 and 2019 for primary posterior fossa brain tumors.

Proton Pencil Beam Scanning Facilitates the Safe Treatment of Extended Radiation Targets for Hodgkin Lymphoma: A Report from the Proton Collaborative Group Registry.

Because proton beam therapy (PBT) can lower the dose of radiation to the heart, lungs, and breast, it is an established radiation modality for patients with Hodgkin lymphoma (HL). Pencil beam scanning (PBS) PBT facilitates the treatment of more extensive targets. This may be especially of value for lymphoma patients who require RT to both mediastinal and axillary targets, defined here as extended target RT (ETRT), given the target distribution and need to minimize the lung, heart, and breast dose.

Risk of Serious Adverse Gastrointestinal Events with Potassium Binders in Hospitalized Patients: A National Study.

Background: Concerns about serious adverse gastrointestinal (GI) events with sodium polystyrene sulfonate (SPS) led to development of two new potassium binders, patiromer and sodium zirconium cyclosilicate (SZC), for treatment of hyperkalemia.

Objective: To compare risk of intestinal ischemia/thrombosis or other serious GI events associated with SPS, patiromer, or SZC in hospitalized patients.

Design: Retrospective cohort study.

IBD Matchmaking: Rational Combination Therapy.

A growing number of patients with Crohn's disease and ulcerative colitis have disease that is refractory to multiple advanced therapies, have undergone multiple surgeries, and require further treatment options. For this reason, there has been increasing use of multiple simultaneous advanced targeted therapies. Although the knowledge on combined advanced targeted therapy (CATT) in inflammatory bowel disease (IBD) has been largely limited to observational data and early-phase randomized controlled trials, combination of therapies is commonplace in many other diseases.

Stereotactic Body Proton Therapy Versus Conventionally Fractionated Proton Therapy for Early Prostate Cancer: A Randomized, Controlled, Phase 3 Trial.

Purpose: We aimed to determine if ultrahypofractionated proton therapy delivered via stereotactic body proton therapy (SBPT) is noninferior to conventionally fractionated proton therapy (CFPT) in patients with early prostate cancer.

Methods And Materials: This study was a multicenter, randomized, controlled, noninferiority phase 3 trial that included patients with histologically confirmed low-risk prostate adenocarcinoma defined by Gleason score grouping 1, Prostate-specific antigen <10 ng/mL, and clinical stage T1-T2a N0 M0 according to 7th edition of the American Joint Committee on Cancer tumor-node-metastasis cancer staging system. Eligible participants were randomly assigned initially at a 1:1 ratio and later at a 2:1 ratio to SBPT (38 Gy in 5 fractions) or CFPT (79.

Reirradiation With Proton Therapy for Recurrent Malignancies of the Esophagus and Gastroesophageal Junction: Results of the Proton Collaborative Group Multi-Institutional Prospective Registry Trial.

Purpose: Treatment options for recurrent esophageal cancer (EC) previously treated with radiation therapy (RT) are limited. Reirradiation (reRT) with proton beam therapy (PBT) can offer lower toxicities by limiting doses to surrounding tissues. In this study, we present the first multi-institutional series reporting on toxicities and outcomes after reRT for locoregionally recurrent EC with PBT.

Clinical characteristics and genetic HLA marker for patients with oxaliplatin-induced adverse drug reactions.

Background: Oxaliplatin is commonly used to treat gastrointestinal malignancies. However, its applications are limited due to potential adverse drug reactions (ADRs), particularly severe anaphylactic shock. There is no method to predict or prevent ADRs caused by oxaliplatin.

Functional Diversity of Memory CD8 T Cells is Spatiotemporally Imprinted.

Tissue-resident memory CD8 T cells (T) kill infected cells and recruit additional immune cells to limit pathogen invasion at barrier sites. Small intestinal (SI) T cells consist of distinct subpopulations with higher expression of effector molecules or greater memory potential. We hypothesized that occupancy of diverse anatomical niches imprints these distinct T transcriptional programs.

Automated Spatial Omics Landscape Analysis Approach Reveals Novel Tissue Architectures in Ulcerative Colitis.

The utility of spatial omics in leveraging cellular interactions in normal and diseased states for precision medicine is hampered by a lack of strategies for matching disease states with spatial heterogeneity-guided cellular annotations. Here we use a spatial context-dependent approach that matches spatial pattern detection to cell annotation. Using this approach in existing datasets from ulcerative colitis patient colonic biopsies, we identified architectural complexities and associated difficult-to-detect rare cell types in ulcerative colitis germinal-center B cell follicles.

Gut microbiota and clinical response to immune checkpoint inhibitor therapy in patients with advanced cancer.

Background: There is currently no well-accepted consensus on the association between gut microbiota and the response to treatment of immune checkpoint inhibitors (ICIs) in patients with advanced cancer.

Methods: Fecal samples were collected before ICI treatment. Gut microbiota was analyzed using 16 S ribosomal RNA sequencing.

Comparative Analysis of Tolerance to Experimentally Induced Astigmatism with Three Types of Multifocal Intraocular Lenses.

Purpose: The effect of residual astigmatism and its axis on distance and near visual acuities (VAs) with multifocal intraocular lenses (IOLs) has not been studied extensively. This study compared the tolerance to experimentally induced residual astigmatism among bifocal, trifocal, and extended depth-of-focus (EDOF) IOLs.

Patients And Methods: This retrospective, comparative study included 70 eyes of 70 patients implanted with bifocal, trifocal, or EDOF IOLs.