Corticotropin 400units/5ml gel for injection vials

BackgroundInsomnia is increasingly recognized as a systemic disorder involving persistent hyperarousal, neuroendocrine dysregulation, immune activation, and impaired stress adaptation. However, circulating biomarkers reflecting these interconnected biological processes have not been comprehensively synthesized.MethodsWe conducted a systematic review and meta-analysis of observational studies comparing circulating biomarkers between adults with insomnia and healthy controls. Standardized mean differences (SMDs) with 95% confidence intervals (CIs) were pooled using random- or fixed-effects models as appropriate. Subgroup analyses, sensitivity analyses, and Grading of Recommendations Assessment, Development and Evaluation (GRADE) assessments were performed to evaluate the robustness and certainty of the evidence.ResultsThirty-two studies involving 4578 individuals with insomnia and 28382 healthy controls were included. Cortisol levels were significantly elevated (SMD = 3.65, 95% CI: 2.35 to 4.95). Inflammatory biomarkers, including interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), C-reactive protein (CRP), interleukin-1β (IL-1β), interleukin-2 (IL-2), and interferon-γ (IFN-γ), were significantly increased, whereas interleukin-4 (IL-4) and interleukin-10 (IL-10) showed no significant differences. Neuropeptide Y (NPY) was significantly reduced (SMD = -0.85, 95% CI: -1.27 to -0.43), while corticotropin-releasing hormone (CRH) and brain-derived neurotrophic factor (BDNF) showed no significant pooled differences. TNF-α, IL-1β, IL-6, CRP, and NPY showed generally consistent results in sensitivity analyses.ConclusionsInsomnia is associated with alterations in circulating biomarkers reflecting hypothalamic-pituitary-adrenal (HPA) axis activity, low-grade systemic inflammation, and potential reductions in stress-buffering capacity. This multidomain biomarker pattern provides insights into the biological basis of insomnia and highlights potential candidate biomarkers for future biological stratification.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD420261396725.

Abstract licence: CC BY

Background: Sarcoidosis is a [chronic granulomatous disease of unknown etiology that predominantly affects the lungs but can involve virtually any organ, including the liver. Pulmonary involvement occurs in over 90% of patients, while hepatic involvement is reported in 5–25% of cases. Despite the expanding therapeutic armamentarium, evidence regarding both pulmonary efficacy and hepatic safety/efficacy of sarcoidosis therapies remains fragmented across heterogeneous studies. This systematic review synthesizes the available evidence on pharmacological therapies for sarcoidosis, with a dual focus on pulmonary outcomes (forced vital capacity, steroid-sparing, radiographic response) and hepatic outcomes (hepatotoxicity, efficacy in hepatic sarcoidosis). Methods: A comprehensive literature search was conducted across PubMed, MEDLINE, Cochrane Library, and ClinicalTrials.gov through May 2025. Studies evaluating pharmacological therapies for sarcoidosis reporting pulmonary and/or hepatic outcomes were included. Therapies were categorized as first-line (glucocorticoids, methotrexate), second-line (antimetabolites, hydroxychloroquine), third-line (anti-TNF biologics, rituximab, repository corticotropin injection), and investigational agents (JAK inhibitors, efzofitimod, antifibrotics). Data were extracted on study design, sample size, pulmonary function outcomes, hepatic efficacy, hepatotoxicity, and adverse events. Quality assessment was performed using the Cochrane Risk of Bias tool for RCTs and the Newcastle-Ottawa Scale for observational studies. Results: A total of 22 therapies across 4 treatment lines were identified with reportable pulmonary and/or hepatic outcome data. The evidence base comprised 8 randomized controlled trials, 8 single-arm trials, multiple retrospective cohort studies, and real-world database analyses. Key findings are summarized by treatment line below. Conclusions: Methotrexate has emerged as a noninferior first-line alternative to prednisone for pulmonary sarcoidosis. Anti-TNF agents, particularly infliximab, provide modest but consistent pulmonary benefit and demonstrate efficacy in hepatic sarcoidosis phenotypes. JAK inhibitors and efzofitimod represent promising investigational therapies. Hepatotoxicity remains a critical consideration across multiple drug classes, necessitating structured monitoring. Prospective studies specifically evaluating hepatic sarcoidosis outcomes are urgently needed.

Abstract licence: CC BY