Immune checkpoint inhibitors (ICIs) harness the immune system and are the therapy of choice for multiple cancers. Although immunosuppressive agents such as steroids are also used in many cancers, it is unknown how their timing affects treatment outcomes. Thus, we investigated the relationship between the timing of steroid exposure preceding ICI administration and subsequent treatment outcomes in melanoma. This population-based study utilized the SEER-Medicare-linked database to identify patients diagnosed with melanoma between 1991 and 2015 and receiving ICIs between 2010 and 2016, examining last steroid exposure in the 12 months preceding ICI. The main outcome was all-cause mortality (ACM) after ICIs. Modifications of the Cox proportional hazards model were used to calculate time-dependent hazards. Of 1671 patients with melanoma receiving ICIs, 907 received steroids. Compared with no steroids, last steroid exposures ≤1 month and 1-3 months prior to ICIs were associated with a 126% and 51% higher ACM within 3 months post ICI initiation, respectively (hazard ratio (HR): 2.26, 95% CI: 1.65-3.08; and HR: 1.51, 95% CI: 1.01-2.27). Steroid exposure within 3 months of initiating ICIs was associated with increased mortality up to 6 months after ICI. Further investigation is warranted to elucidate mechanisms affecting outcomes due to steroids.
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http://dx.doi.org/10.3390/cancers14051296 | DOI Listing |
Fish Physiol Biochem
January 2025
Neurobiology Program, Sirius University of Science and Technology, Sochi, Russia.
Stress plays a key role in mental, neurological, endocrine, and immune disorders. The zebrafish (Danio rerio) is rapidly gaining popularity as s model organism in stress physiology and neuroscience research. Although the leopard (leo) fish are a common outbred zebrafish strain, their behavioral phenotypes and stress responses remain poorly characterized.
View Article and Find Full Text PDFRheumatol Int
January 2025
Department of Rheumatology, Immunology and Internal Medicine, University Hospital in Kraków, Kraków, Poland.
Systemic lupus erythematosus (SLE) is a multisystem autoimmune rheumatic disease (ARD) that results from the dysregulation of multiple innate and adaptive immune pathways. Late-onset SLE (Lo-SLE) is the term used when the disease is first diagnosed after 50-65 years, though the standard age cut-off remains undefined. Defining "late-onset" as lupus with onset after 50 years is more biologically plausible as this roughly corresponds to the age of menopause.
View Article and Find Full Text PDFInflamm Res
January 2025
Institute of Allergy and Clinical Immunology, Biomedical Research Institute, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul, 110-744, Republic of Korea.
Particulate matter (PM) exposure has been proposed as one of the causes of steroid resistance. However, studies investigating this using patient samples or animals are still lacking. Therefore, in this study, we aimed to investigate the changes in cytokines and mTOR (mammalian target of rapamycin) activation in patients with steroid resistant asthma and the role of mTOR in a mouse model of steroid resistant asthma induced by PM.
View Article and Find Full Text PDFJ Bone Joint Surg Am
January 2025
Department of Orthopaedic Surgery, Keck School of Medicine of the University of Southern California, Los Angeles, California.
Background: Complete blood cell count-based ratios (CBRs), including the neutrophil-lymphocyte ratio (NLR) and monocyte-lymphocyte ratio (MLR), are inflammatory markers associated with postoperative morbidity. Given the link between the surgical stress response and complications after total joint arthroplasty (TJA), this study aimed to evaluate whether higher preoperative CBR values predict greater postoperative benefits associated with dexamethasone utilization.
Methods: The Premier Healthcare Database was queried for adult patients who underwent primary, elective total hip or knee arthroplasty (THA or TKA).
Aliment Pharmacol Ther
January 2025
Division of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
Background: The pharmacokinetics of biologic agents can differ between children and adults with inflammatory bowel disease (IBD), often necessitating modified paediatric dosing strategies.
Aims: To define the exposure-response relationship of vedolizumab in the paediatric IBD VedoKids cohort including the effect of baseline clearance on deep biochemical remission (normal C-reactive protein [CRP]/erythrocyte sedimentation rate [ESR] and steroid-free remission) at 30 weeks, and to use population pharmacokinetic models to find the best matches between adult and paediatric pharmacokinetic profiles.
Methods: We sought a pharmacokinetic model on 312 serum vedolizumab concentrations from 129 children, assisted by a published adult model as a Bayesian prior.
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