Activity of osimeRTInib in non-small-cell lung Cancer with UNcommon epidermal growth factor receptor mutations: retrospective Observational multicenter study (ARTICUNO).

BACKGROUND: Osimertinib represents the standard of care for the treatment of advanced non-small-cell lung cancer (NSCLC) harboring classical epidermal growth factor receptor (EGFR) mutations, constituting 80%-90% of all EGFR alterations. In the remaining cases, an assorted group of uncommon alterations of EGFR (uEGFR) can be detected, which confer variable sensitivity to previous generations of EGFR inhibitors, overall with lower therapeutic activity. Data on osimertinib in this setting are limited and strongly warranted. PATIENTS AND METHODS: The ARTICUNO study retrospectively evaluated data on osimertinib activity from patients with advanced NSCLC harboring uEGFR treated in 21 clinical centers between August 2017 and March 2023. Data analysis was carried out with a descriptive aim. Investigators collected response data according to RECIST version 1.1 criteria. The median duration of response, progression-free survival (mPFS), and overall survival were estimated by the Kaplan-Meier method. RESULTS: Eighty-six patients harboring uEGFR and treated with osimertinib were identified. Patients with 'major' uEGFR, that is, G719X, L861X, and S768I mutations (n = 51), had an overall response rate (ORR) and mPFS of 50% and 9 months, respectively. Variable outcomes were registered in cases with rarer 'minor' mutations (n = 27), with ORR and mPFS of 31% and 4 months, respectively. Among seven patients with exon 20 insertions, ORR was 14%, while the best outcome was registered among patients with compound mutations including at least one classical EGFR mutation (n = 13). Thirty patients presented brain metastases (BMs) and intracranial ORR and mPFS were 58% and 9 months, respectively. Amplification of EGFR or MET, TP53 mutations, and EGFR E709K emerged after osimertinib failure in a dataset of 18 patients with available rebiopsy. CONCLUSION: The ARTICUNO study confirms the activity of osimertinib in patients with uEGFR, especially in those with compound uncommon-common mutations, or major uEGFR, even in the presence of BMs. Alterations at the E709 residue of EGFR are associated with resistance to osimertinib.

ISO 9001:2015 standard implementation in clinical trial centers: An exploratory analysis of benefits and barriers in Italy.

Background: In the last decade many clinical research centers in Italy have increasingly implemented and improved their quality standards and effectiveness of processes through the adoption of a quality management system also according to the certification ISO 9001:2015. Objective: The aim of this project is to evaluate expected benefits and barriers of ISO 9001 certification for a Clinical Trial Center. Material and methods: On April 2021, the Italian Group of Data Manager and Clinical Research Coordinator spread an anonymous online survey to healthcare professionals operating in clinical research and quality management systems at research sites. Results: Reported benefits of ISO oriented Quality Management System adoption include continual improvement and better-quality processes (73.3%), assuring corrective actions (63.6%), planning internal audits (60.2%) and risk management approach (60.7%). The most important barriers to QMS implementation are increased logistical and/or organizational activities (40.9%) and insufficient training on quality programs (29.5%). Conclusions: Implementing a quality management system represents a challenge for the Clinical Trial Center and helps to improve quality standards and risk management approach. The use of electronic tools is poor and could be increased in the future. Lastly, improvement of continuous QMS trainings should be necessary for updating professionals and optimizing activities within the Clinical Trial Center.

Epidural steroids as a pharmacological approach.

Cervicogenic headache is a relatively common pain syndrome related to functional and/or degenerative alterations of the cervical spine tract. Administration of steroid represents an effective therapy for this headache, due to the anti-inflammatory effects combined with its direct analgesic effects on the C fibers. The epidural injection of steroids, while requesting skilled personnel for its execution, gives short term (2-month) pain relief with few risks or side effects. Moreover, epidural steroids allow reduction of analgesic drug consumption.

Resistance to antibiotics targeted to the bacterial cell wall.

Peptidoglycan is the main component of the bacterial cell wall. It is a complex, three-dimensional mesh that surrounds the entire cell and is composed of strands of alternating glycan units crosslinked by short peptides. Its biosynthetic machinery has been, for the past five decades, a preferred target for the discovery of antibacterials. Synthesis of the peptidoglycan occurs sequentially within three cellular compartments (cytoplasm, membrane, and periplasm), and inhibitors of proteins that catalyze each stage have been identified, although not all are applicable for clinical use. A number of these antimicrobials, however, have been rendered inactive by resistance mechanisms. The employment of structural biology techniques has been instrumental in the understanding of such processes, as well as the development of strategies to overcome them. This review provides an overview of resistance mechanisms developed toward antibiotics that target bacterial cell wall precursors and its biosynthetic machinery. Strategies toward the development of novel inhibitors that could overcome resistance are also discussed.

Simplifying scleral fixation of posterior chamber intraocular lenses.

We describe a surgical modification for primary scleral fixation of posterior chamber intraocular lenses. The technique keeps intraocular surgical manipulation at a minimum and allows fixation of the lens during accidental rupture of the posterior lens capsule.

Restriction fragment length polymorphism (RFLP) of exon 2 of the MhcBibi-DRB3 gene in American bison (Bison bison).

Polymerase chain reaction (PCR) primers specific to exon 2 of the bovine lymphocyte antigen (BoLA)-DRB3 gene were successfully used to amplify the equivalent region in 469 American bison (Bison bison). In domestic cattle, alleles of DRB3 are assigned through a restriction fragment length polymorphism (RFLP) analysis of the patterns of fragment lengths observed after digestion with the restriction enzymes RsaI, BstYI and HaeIII. In bison, using the same procedure, the observed RFLP patterns provided evidence for the strong conservation of restriction sites previously reported in cattle.

A comparative analysis of Mhc DRB3 polymorphism in the American bison (Bison bison).

The degree of genetic polymorphism at the DRB3 locus in the major histocompatibility complex (Mhc) of the North American bison was investigated by PCR and DNA sequence analysis. Nine different alleles were characterized in a selected sample of 20 animals. The genetic distances between alleles were as large as usually found at highly polymorphic Mhc loci in other species. A comparative analysis of the DRB3 polymorphism in bison and cattle revealed an extensive sharing of sequence motifs. The result clearly shows a transspecies persistence of DRB3 allelic lineages in the two species. Consequently a significant amount of Mhc polymorphism has been maintained through the population bottleneck that bison experienced in the late nineteenth century. An analysis of the pattern of sequence polymorphism among bison and cattle DRB3 alleles strongly suggested that interallelic recombination has contributed significantly to the generation of allelic diversity at this locus.

Sindrome de Adie e lente multifocal. / Adie's syndrome and multifocal lens

Descricao de um caso tipico de sindrome de Adie. Durante o periodo de convalescencia, garantiu-se uma boa cooperacao binocular mediante o uso de lente multifocal no olho afetado. Pacientes com grande exigencia visual podem ser grandemente beneficiados com esse procedimento