Escalation to Biologics After Methotrexate Among US Veterans With Rheumatoid Arthritis Grouped by Rural Versus Urban Areas.

Objective: Racial and ethnic disparities in rheumatoid arthritis (RA) outcomes are well recognized. However, whether disparities in RA treatment selection and outcomes differ by urban versus rural residence, independent of race, have not been studied. Our objective was to evaluate whether biologic disease-modifying antirheumatic drug (bDMARD) initiation after methotrexate administration differs by rural versus urban residence among veterans with RA.

Unveiling the resistance to therapies in pancreatic ductal adenocarcinoma.

Despite the ongoing advances in interventional strategies (surgery, chemotherapy, radiotherapy, and immunotherapy) for managing pancreatic ductal adenocarcinoma (PDAC), the development of therapy refractory phenotypes remains a significant challenge. Resistance to various therapeutic modalities in PDAC emanates from a combination of inherent and acquired factors and is attributable to cancer cell-intrinsic and -extrinsic mechanisms. The critical determinants of therapy resistance include oncogenic signaling and epigenetic modifications that drive cancer cell stemness and metabolic adaptations, CAF-mediated stromagenesis that results in ECM deposition altered mechanotransduction, and secretome and immune evasion.

Efficacy and safety of sintilimab in combination with chemotherapy for recurrent extensive-stage small cell lung cancer: a real-world retrospective study.

Background: Immune checkpoint inhibitors (ICIs) no longer are approved for second-line or later treatment of extensive-stage small cell lung cancer (ES-SCLC), and have not been studied in combination with chemotherapy. Exploring the efficacy and safety of second-line or later immunotherapy for ES-SCLC is an urgent clinical question that needs to be addressed, and combination therapies are an important research direction. This study intended to investigate the efficacy and safety of the sintilimab in combination with chemotherapy as a second-line and beyond treatment option for ES-SCLC.

Analysis of Circulating Tumor DNA Predicts Outcomes of Short-Course Consolidation Immunotherapy in Unresectable Stage III NSCLC.

Introduction: The current standard of care for patients with inoperable stage III non-small cell lung cancer includes chemoradiotherapy (CRT) followed by 1 year of checkpoint inhibitor (CPI) therapy. Nevertheless, the optimal duration of consolidation CPI remains unknown. Here, we characterized the relationship between circulating tumor DNA (ctDNA) minimal residual disease (MRD) and clinical outcomes of patients with unresectable locally advanced non-small cell lung cancer treated on a phase 2 trial of short-course consolidation immunotherapy after CRT, with the goal of testing whether ctDNA may be able to identify patients who do not require a full year of treatment.

Quality of Life and Depression Symptoms After Therapy De-Escalation in HPV+ Oropharyngeal Squamous Cell Carcinoma: A Nonrandomized Controlled Trial.

Importance: Despite interest in therapy de-escalation for survivors of human papillomavirus-mediated oropharyngeal squamous cell carcinoma (HPV-positive OPSCC), the association of de-escalated therapy with patient-reported quality of life (QoL) outcomes and burden of depressive symptoms remains unclear.

Objective: To identify associations between clinicopathologic and therapeutic variables with patient-reported QoL outcomes and depression symptom burden in patients with HPV-positive OPSCC, who were enrolled in a therapy de-escalation trial.

Design, Setting, And Participants: In this nonrandomized controlled, open-label, curative-intent therapy de-escalation clinical trial in adults with stage I, II, and III HPV-positive OPSCC, patients were recruited from a high-volume head and neck oncology practice.

Plasma Matrix Metalloproteinase Concentrations and Risk of Interstitial Lung Disease in a Prospective Rheumatoid Arthritis Cohort.

Objective: To evaluate the associations of plasma matrix metalloproteinases (MMPs) with prevalent and incident interstitial lung disease (ILD) in people with rheumatoid arthritis (RA).

Methods: Within a multicenter, prospective cohort of US veterans with RA, we performed a cross-sectional study of prevalent ILD and cohort study of incident ILD. ILD diagnoses were validated by medical record review of provider diagnoses and chest imaging and/or pathology reports.

Psychometric Properties of Frailty Instruments in Adults With Rheumatoid Arthritis: A Systematic Review.

Objective: Examine psychometric properties of frailty instruments used in adults with rheumatoid arthritis (RA) to inform selection of frailty instruments for clinical and research use.

Methods: A systematic review was registered in PROSPERO. Studies measuring frailty in adults with RA published before May 25, 2022, were searched in six electronic databases.

Determinants of Achieving Serum Urate Goal with Treat-to-Target Urate-Lowering Therapy in Gout.

Objective: Using trial data comparing treat-to-target allopurinol and febuxostat in gout, we examined participant characteristics associated with serum urate (SU) goal achievement.

Methods: Participants with gout and SU ≥6.8 mg/dL were randomized to allopurinol or febuxostat, titrated during weeks 0 to 24, and maintained weeks 25 to 48.

Corticosteroid Injections for Symptomatic Treatment of Osteoarthritis of the Knee: A Pilot Blinded Randomized Trial.

Objective: To quantify the effect of corticosteroids compared to lidocaine-only injections over 12 weeks among patients with knee osteoarthritis (KOA).

Methods: Participants with KOA were randomized to receive a knee injection of methylprednisolone acetate 1 mL (40 mg) plus 2 mL lidocaine (1%) or 1 mL saline and 2 mL lidocaine. Participants and providers were blinded to treatment allocation using an opacified syringe.

Chimeric antibody targeting unique epitope on onco-mucin16 reduces tumor burden in pancreatic and lung malignancies.

Aberrantly expressed onco-mucin 16 (MUC16) and its post-cleavage generated surface tethered carboxy-terminal (MUC16-Cter) domain are strongly associated with poor prognosis and lethality of pancreatic (PC) and non-small cell lung cancer (NSCLC). To date, most anti-MUC16 antibodies are directed towards the extracellular domain of MUC16 (CA125), which is usually cleaved and shed in the circulation hence obscuring antibody accessibility to the cancer cells. Herein, we establish the utility of targeting a post-cleavage generated, surface-tethered oncogenic MUC16 carboxy-terminal (MUC16-Cter) domain by using a novel chimeric antibody in human IgG1 format, ch5E6, whose epitope expression directly correlates with disease severity in both cancers.

Multimorbidity Patterns and Rheumatoid Arthritis Disease Outcomes: Findings From a Multicenter, Prospective Cohort.

Objective: To determine whether unique multimorbidity patterns are associated with long-term rheumatoid arthritis (RA) disease severity.

Methods: We conducted a cohort study within the Veterans Affairs Rheumatoid Arthritis registry. We applied previously derived multimorbidity patterns based on the presence of diagnostic codes for relevant conditions prior to enrollment using linked administrative data.

Updating and Validating the Rheumatic Disease Comorbidity Index to Incorporate ICD-10-CM Diagnostic Codes.

Objective: To update and validate the Rheumatic Disease Comorbidity Index (RDCI) utilizing International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) codes.

Methods: We defined ICD-9-CM (n = 1,068) and ICD-10-CM (n = 1,425) era cohorts (n = 862 in both) spanning the ICD-9-CM to ICD-10-CM transition in a multicenter, prospective rheumatoid arthritis registry. Information regarding comorbidities was collected from linked administrative data over 2-year assessment periods.

Risk factors of SARS-CoV-2 infection and complications from COVID-19 in lung cancer patients.

Background: Identifying lung cancer patients at an increased risk of getting SARS-CoV-2-related complications will facilitate tailored therapy to maximize the benefit of anti-cancer therapy, while decreasing the likelihood of COVID-19 complications. This analysis aimed to identify the characteristics of lung cancer patients that predict for increased risk of death or serious SARS-CoV-2 infection.

Patients And Methods: This was a retrospective cohort study of patients with lung cancer diagnosed October 1, 2015, and December 1, 2020, and a diagnosis of COVID-19 between February 2, 2020, and December 1, 2020, within the Veterans Health Administration.

A Narrowing Mortality Gap: Temporal Trends of Cause-Specific Mortality in a National Matched Cohort Study in US Veterans With Rheumatoid Arthritis.

Objective: To examine temporal trends in all-cause and cause-specific mortality in patients with rheumatoid arthritis (RA) in the Veterans Health Administration (VHA).

Methods: We conducted a matched cohort study in the VHA from January 1, 2000 to December 31, 2017. Incident RA patients were matched up to 1:10 on age, sex, and VHA enrollment year to non-RA patients, then followed until death or end of study period.

Risk of malignancy in patients with chronic kidney disease.

Background: Fifteen percent of US adults have chronic kidney disease (CKD). The effect of CKD on the development of different malignancies is unknown. Understanding the effect of CKD on the risk of development of cancer could have important implications for screening and early detection of cancer in these patients.

Risk of Prostate Cancer in US Veterans With Rheumatoid Arthritis.

Objective: Patients with rheumatoid arthritis (RA) have an increased risk of select cancers, including lymphoma and lung cancer. Whether RA influences prostate cancer risk is uncertain. We aimed to determine the risk of prostate cancer in patients with RA compared to patients without RA in the Veterans Health Administration (VA).

Identification of Multimorbidity Patterns in Rheumatoid Arthritis Through Machine Learning.

Objective: Recognizing that the interrelationships between chronic conditions that complicate rheumatoid arthritis (RA) are poorly understood, we aimed to identify patterns of multimorbidity and to define their prevalence in RA through machine learning.

Methods: We constructed RA and age- and sex-matched (1:1) non-RA cohorts within a large commercial insurance database (MarketScan) and the Veterans Health Administration (VHA). Chronic conditions (n = 44) were identified from diagnosis codes from outpatient and inpatient encounters.

Circulating Adipokines and Associations With Incident Cardiovascular Disease in Rheumatoid Arthritis.

Objective: To assess whether circulating levels of adiponectin, leptin, and fibroblast growth factor 21 (FGF-21) are associated with incident cardiovascular disease (CVD) in rheumatoid arthritis (RA).

Methods: Adipokines were measured using banked enrollment serum from patients with RA and dichotomized above/below the median value. Incident CVD events (coronary artery disease [CAD], stroke, heart failure [HF] hospitalization, venous thromboembolism, CVD-related deaths) were identified using administrative data and the National Death Index.

Cause-Specific Mortality in Patients With Gout in the US Veterans Health Administration: A Matched Cohort Study.

Objective: To compare all-cause and cause-specific mortality risk between patients with gout and patients without gout in the Veteran's Health Administration (VHA).

Methods: We performed a matched cohort study, identifying patients with gout in the VHA from January 1999 to September 2015 based on the presence of ≥2 International Classification of Diseases, Ninth Revision codes for gout (274.X).

Senescence marker protein 30 inhibits tumor growth by reducing HDAC4 expression in non-small cell lung cancer.

Background: Senescence marker protein 30 (), which plays a pivotal role as a suppressor protein in cell proliferation, among other regulatory actions, is a marker of aging that shows decreased expression during senescence. Decreased has been identified in several human cancers, but its expression and role in human non-small cell lung cancer (NSCLC) remain unclear.

Methods: Using tumor tissue and matched adjacent normal tissue from 341 patients with resected NSCLC, we assessed expression using immunohistochemical methods.

Risk of COVID-19 in Rheumatoid Arthritis: A National Veterans Affairs Matched Cohort Study in At-Risk Individuals.

Objective: Rheumatoid arthritis (RA) and its treatments are associated with an increased risk of infection, but it remains unclear whether these factors have an impact on the risk or severity of COVID-19. The present study was undertaken to assess the risk and severity of COVID-19 in a US Department of Veterans Affairs (VA) cohort of patients with RA and those without RA.

Methods: A matched cohort study using national VA data was conducted.