This phase 2 nonrandomized clinical trial evaluated oral upadacitinib for severe immune checkpoint inhibitor–related dermatitis in patients with solid tumors.
Rash resolution to grade ≤1 was achieved in all participants within 28 days, and pruritus improvement was reported within 1 day of initiation. Upadacitinib was well tolerated, with no serious treatment-related adverse events.
The majority of patients were able to continue immune checkpoint inhibitor therapy as scheduled, indicating the potential of upadacitinib as a safe and effective option for managing severe Dermatitis induced by immunotherapy.
This nonrandomized clinical trial examines the safety and efficacy of oral upadacitinib in the treatment of patients with severe immune checkpoint inhibitor–related dermatitis.
[Alzheimer’s disease: AD] Zhang et al.: “Increased theta band power was statistically significant in AD patients, highlighting its critical role in AD pathology.”
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ObjectivesWe report on a patient with a distinct clinical and neuroradiologic phenotype and a de novo variant in the FTH1 gene. MethodsThe patient was a 25-year-old woman with developmental delay and pontocerebellar hypoplasia, who after years of stable condition visited our hospital at age 20 years because of clinical deterioration. With consent from the patients’ family, we obtained clinical, imaging, and genetic data from the patient’s medical record.
Microglial replacement strategy to treat microgliopathy.
Colony-stimulating factor 1 receptor (CSF1R) gene mutation (I794T) is linked to primary microgliopathy manifesting as leukoencephalopathy.
The researchers define the clinical features of patients carrying the CSF1R p. I794T variant and establish a corresponding knockin mouse model.
The authors demonstrate that knockin mice exhibited hallmark features of CSF1R-related disorder (CSF1R-RD).
They show that Csf1rI792T/+ microglia adopt a disease associated state and that a microglial replacement strategy termed “duplicate-cyclic microglial depletion for transplantation” (DCMDT), mitigates cognitive and neuropathological deficits in CSF1R-RD. sciencenewshighlights ScienceMission https://sciencemission.com/microglia-replacement-18450
Li et al. define the clinical features of patients carrying the CSF1R p. I794T variant and establish a corresponding knockin mouse model. They show that Csf1rI792T/+ microglia adopt a disease-associated state and that a microglial replacement strategy, DCMDT, mitigates cognitive and neuropathological deficits in CSF1R-related disorder.
📊 Research Summary: The ImmunoSep trial demonstrates the potential for biomarker-guided immunotherapy in a subset of patients with sepsis.
This trial assessed whether immunotherapy tailored to individual immune dysregulation—macrophage activation–like syndrome and sepsis-induced immunoparalysis—could improve organ function among patients with sepsis-3.
Fungal infections present persistent therapeutic challenges in immunocompromised populations, including individuals with acquired immunodeficiency syndrome (AIDS), organ transplant recipients receiving immunosuppressive therapy, long-term hospitalized patients, patients with cancer, and those receiving immunomodulatory agents.1 These infections demonstrate remarkable recalcitrance to conventional therapies, compounded by fungal adaptability to environmental stresses, the emergence of drug-resistant strains, and the limited availability of clinically available antifungal agents.2 Systemic fungemia has alarmingly high mortality rates, accounting for approximately 1.5 million annual deaths worldwide, a burden comparable to AIDS-and tuberculosis-related mortality.3 Candida albicans is the most frequently isolated fungal pathogen in clinical settings. Despite therapeutic advances, invasive candidiasis persists with mortality rates exceeding 40%,4 underscoring the urgent need to elucidate host immune mechanisms against fungal pathogens.
When innate immune cells, such as macrophages, dendritic cells, and neutrophils, encounter fungi, the pattern recognition receptors (PRRs) on their surface recognize evolutionarily conserved fungal cell wall components, including β-glucan and α-mannan (classified as pathogen-associated molecular patterns), thereby initiating downstream signaling cascades and immune responses. The primary PRRs involved in fungal recognition are C-type lectin receptors (CLRs) and Toll-like receptors. The CLR family comprises Dectin-1 (specific for β-glucan), Dectin-2/3 (mannan sensors), Mincle, dendritic cell-specific intercellular adhesion molecule-grabbing nonintegrin, and CD23.5 Upon ligand binding, CLRs initiate the phosphorylation of the immunoreceptor tyrosine-based activation motif within the Dectin-1 cytoplasmic tail and the recruitment of the Fc receptor γ-chain to Dectin-2 or Mincle, which serves as a docking site for spleen tyrosine kinase (SYK).
