Association of Systemic Steroid Treatment and Outcome in Patients Treated with Immune Checkpoint Inhibitors: A Real-World Analysis

Background: Immune-related adverse events (irAEs) are inflammatory side effects, which can occur during immune-checkpoint(s) inhibitors (ICIs) therapy. Steroids are the first-line agents to manage irAEs because of their immunosuppressive properties. However, it is still debated whether or when steroids can be administered without abrogating the therapeutic efforts of immunotherapy. Methods: We retrospectively evaluated 146 patients with metastatic non-small cell lung cancer (NSCLC), melanoma and renal cell carcinoma (RCC) treated with ICIs. We assessed the progression-free survival (PFS) of patients treated with steroids due to an irAE compared to a no-steroid group. Results: The early treatment with steroid (within the first 30 days from the beginning of immunotherapy) was not related to a shorter PFS (p = 0.077). Interestingly, patients who were treated with steroids after 30 days from the start of immunotherapy had significantly longer PFS (p = 0.017). In a multivariate analysis, treatment with steroids after 30 days was an independent prognostic factor for PFS (HR: 0.59 [95% CI 0.36–0.97], p = 0.037). Conclusions: This retrospective study points out that early systemic steroids administration to manage irAEs might not have a detrimental effect on patient clinical outcome in NSCLC, melanoma and RCC patients.     

Oxazoles as masked activated carboxylates. Synthesis of (±)-di-O-methylcurvularin

The dimethyl ether of the mold metabolite, curvularin, was synthesized by intramolecular esterification of an activated carboxylate derived from the photooxidation of an oxazole precursor.     

Activated carboxylates from the photooxygenation of oxazoles. Application to the synthesis of recifeiolide and other macrocyclic lactones.

The oxazole system may serve as a protecting group for the carboxyl function. The carboxylate is generated under the mild conditions of photooxygenation in high yield in the form of the reactive triamide. This reaction has been applied to the synthesis of macrocyclic lactones.     

Fungi allergens produced by solid-state fermentation process

Allergenic extracts were produced from Drechslera (Helminthosporium) monoceras biomass cultured by solid-state fermentation using wheat bran as the substrate. The main fermentation variables were selected by statistical design, and the optimized biomass yield (1.43 mg/[g of dry substrate · d]) was obtained at pH 9.5 and 45.8% moisture. The allergenic extracts were produced from crude extract by protein precipitation and polyphenol removal. Proteins in the range of 16–160 kDa were identified in the extracts. Their reactions in patients were characterized by in vivo cutaneous tests (positive in 40% of the atopic patients) and by dot-blotting assays.     

Activated carboxylates from the photooxygenation of oxazoles : Application to the synthesis of recifeiolide,curvularin and other macrolides

Oxazoles may be used as masked forms of activated carboxylic acids since they readily form triamides on reaction with singlet oxygen. With 2-alkyl-4,5-diphenyloxazoles, the triamides formed on photooxygenation undergo selective nucleophilic attack at the acyl carbonyl derived from the 2-oxazole position. Using 2-(ω- hydroxyalkyl)-4,5- diphenyloxazoles as substrates, the oxidation-acylation sequence may be employed for the synthesis of macrolides including (±)-recifeiolide and (±)-di-0-methylcurvularin.