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First-line treatment of endogenous Cushing's syndrome (CS) is surgical removal of the tumor responsible for cortisol excess. However, medical therapy has an established role in treatment when patients are not surgical candidates or decline surgery, residual or recurrent disease is present and not amenable to repeat resection, and control of hypercortisolism is needed either preoperatively or while awaiting the effects of radiotherapy. The approach to medical therapy should be tailored based on the etiology, degree of hypercortisolism, and patient characteristics. Currently available medical therapy for all etiologies of CS either blocks adrenal production of cortisol or blocks its action at the level of the glucocorticoid receptor. Currently available medical therapy for Cushing's disease (CD) targets the adrenocorticotropic hormone-secreting pituitary tumor through activation of somatostatin and dopamine receptors, alkylating DNA damage, or immune system activation. More focused therapy with greater efficacy and fewer adverse effects is needed, particularly in the case of CD, with potential targets and drugs identified and in development.

Objectives: Our objective was to systematically synthesize and evaluate the existing evidence from meta-syntheses (systematic reviews and meta-analyses) reporting on the safety of celecoxib in adults with chronic musculoskeletal disorders.

Methods: We conducted a comprehensive literature search in November 2024 across MEDLINE, Cochrane Central, and Scopus databases, following Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines for umbrella reviews. Only systematic reviews and meta-analyses involving celecoxib safety in osteoarthritis, rheumatoid arthritis, or ankylosing spondylitis were included. We assessed the risk of bias using the AMSTAR-2 tool and graded the certainty of evidence using GRADE.

Results: Of 2294 retrieved records, 16 systematic reviews based on randomized controlled trials met the inclusion criteria (14 of 16 were rated as critically low quality). Celecoxib was consistently associated with a lower risk of gastroduodenal ulcers than were non-selective non-steroidal anti-inflammatory drugs (NSAIDs), and some studies also reported fewer gastrointestinal complaints and serious events with celecoxib than with non-selective NSAIDs. Cardiovascular safety outcomes were generally similar to those with non-selective NSAIDs, although one meta-analysis showed a lower risk of cardiovascular mortality with celecoxib. Compared with placebo or non-selective NSAIDs, celecoxib did not increase the risk of renal dysfunction or elevated creatinine and may be associated with fewer renal adverse events. Evidence on all-cause mortality was limited and inconsistent, but one study suggested a lower risk than with non-selective NSAIDs.

Conclusions: Celecoxib appears to offer better gastrointestinal safety than non-selective NSAIDs. Although data on cardiovascular, renal, and mortality outcomes suggest possible advantages, the evidence remains limited and of low certainty. Moreover, some real-world evidence raises concerns in specific high-risk populations. Future research should integrate data from both randomized trials and observational studies to better inform long-term safety assessments and guide individualized treatment decisions.

Acoltremon (TRYPTYR^®) is a TRPM8 thermoreceptor agonist formulated as eye drops, which has been developed by Alcon for the treatment of dry eye disease. As an insufficient aqueous layer is linked to dry eye disease, the stimulation of tear production by acoltremon can relieve symptoms associated with dry eye disease. During phase III trials in patients with dry eye disease, acoltremon demonstrated increased tear production with a low treatment discontinuation rate. This article summarizes the milestones in the development of acoltremon leading to this first approval for the treatment of the signs and symptoms of dry eye disease.

Measurable (or minimal) residual disease (MRD) testing offers critical prognostic insight in multiple myeloma (MM), surpassing conventional response criteria. While bone-marrow-based assays are most commonly performed, MRD assessment in peripheral blood and advanced imaging may add complementary value. A comprehensive approach, integrating serial MRD testing across compartments, may offer the most accurate appraisal of disease burden. MRD has been validated as a surrogate endpoint for accelerated approval (AA) of MM therapies and is increasingly adopted as a key clinical trial endpoint. Ongoing phase 3 trials are using MRD status to tailor consolidation and maintenance strategies, and emerging evidence supports its role in guiding treatment de-escalation, including discontinuation of maintenance therapy. However, barriers remain to implementing MRD as a treatment goal, including cost, complexity of interpreting results, and uncertainty around the optimal timing for guiding decision-making. Moreover, there is a paucity of data on the use of MRD resurgence to prompt changes in therapy. While MRD negativity represents a compelling endpoint in both clinical practice and research, prospective randomized studies will help to better elucidate how best to incorporate MRD into the MM treatment paradigm.

Insulin icodec (icodec) is a first-in-class once-weekly basal insulin approved for the treatment of adults with type 1 diabetes (T1D) and type 2 diabetes (T2D). Healthcare professionals (HCPs) may benefit from clear and practical guidance on translating the use of icodec from a controlled clinical trial setting into real-world clinical practice to ensure its appropriate implementation. Here, we primarily review the available evidence for icodec in T2D to provide evidence-based clinical recommendations and expert opinions to guide the use of icodec in a clinical setting. The pharmacology of icodec is summarized, along with an overview of the results from the ONWARDS 1-6 clinical trials (NCT04460885, NCT04770532, NCT04795531, NCT04880850, NCT04760626, NCT04848480). Key guidance on the practical use of icodec, including treatment initiation, switching to icodec from a once- or twice-daily basal insulin, switching from icodec back to a daily basal insulin, and dose titration, is provided. Icodec usage in special populations and practical situations (e.g., elderly and pediatric individuals, hepatic and renal impairment, hospitalized individuals, and those who are pregnant or planning pregnancy) is discussed. Considerations for glucose monitoring and management, as well as co-administration of icodec with other non-insulin glucose-lowering medications, are provided. Finally, we also briefly summarize the available evidence on icodec use in individuals with T1D, although the primary focus of this review is on its use in T2D. This review provides a comprehensive information resource for HCPs regarding the use of icodec in clinical practice.

Tirofiban is a selective inhibitor of the glycoprotein IIb/IIIa receptor that reversibly prevents platelet aggregation and clot formation-processes central to the development and progression of ischemic stroke. Its use has been widely studied in both laboratory and clinical settings, particularly as an early intervention, a rescue option after failed mechanical thrombectomy, and in combination with clot-dissolving therapies. Emerging evidence supports tirofiban's role in preventing stroke progression, especially in high-risk groups such as older adults, women around menopause, patients with diabetes, liver or kidney dysfunction, and those who are pregnant. The drug has generally shown good safety and effectiveness in promoting blood flow restoration and improving long-term recovery. However, the most effective dosing, treatment scenarios, and patient profiles remain uncertain. Given its strong antiplatelet action and potential protective effects on brain tissue, tirofiban continues to gain interest as a treatment for acute ischemic stroke. This review summarizes key studies published since 2018, based on a structured literature search of PubMed, Embase, and Web of Science through May 2025, with the goal of guiding future research and improving clinical integration.

Pulmonary alveolar proteinosis is suspected when a "crazy paving" pattern is observed on a chest CT scan. This diagnosis is confirmed by the presence of eosinophilic extracellular material that shows positive staining with Periodic Acid Schiff on bronchoalveolar lavage samples. The autoimmune form of pulmonary alveolar proteinosis is confirmed by detecting anti-granulocyte-macrophage colony-stimulating factor antibodies in the patient's serum. The historical first-line treatment for autoimmune pulmonary alveolar proteinosis is whole lung lavage, which should only be performed in expert centers. It remains the preferred treatment for patients experiencing respiratory failure, especially at the time of diagnosis. Inhaled granulocyte-macrophage colony-stimulating factor supplementation with molgramostim or sargramostim is now considered a first-line treatment in the international guidelines for autoimmune pulmonary alveolar proteinosis, following the positive results of recent randomized placebo-controlled studies. Rituximab and plasmapheresis can be prescribed as third- and fourth-line treatments, respectively. Lung transplantation may be considered for eligible patients experiencing terminal respiratory failure. A deeper understanding of the pathogenesis of autoimmune pulmonary alveolar proteinosis has opened up new therapeutic avenues, such as the use of PPARγ agonists or statins.

Atrasentan (VANRAFIA^®), a potent, highly selective, orally administered endothelin type A (ET_A) receptor antagonist, is in development by Novartis for the treatment of glomerular disease. In April 2025, atrasentan was approved in the USA (under accelerated approval based on a reduction in proteinuria) to reduce proteinuria in adults with primary IgA nephropathy (IgAN) at risk of rapid disease progression, generally a urine protein-to-creatinine ratio (UPCR) ≥ 1.5 g/g. It has not been established whether atrasentan slows kidney function decline in patients with IgAN. This article summarizes the milestones in the development of atrasentan leading to this first approval for the reduction of proteinuria in adults with primary IgAN at risk of rapid disease progression.

Linvoseltamab (Lynozyfic™) is a human B cell maturation antigen (BCMA)×cluster of differentiation (CD) 3 bispecific antibody that binds to both BCMA and CD3 to direct T cells against malignant B cells. Linvoseltamab is being developed by Regeneron Pharmaceuticals, Inc. for multiple indications including multiple myeloma and received its first approval on 28 Apr 2025 in the EU. This article summarises the milestones in the development of linvoseltamab leading to this first approval in the EU as monotherapy for the treatment of adult patients with relapsed/refractory multiple myeloma who have received ≥ 3 prior therapies, including a proteasome inhibitor, an immunomodulatory agent and an anti-CD38 monoclonal antibody, and have demonstrated disease progression on the last therapy.