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Background: While targeted therapies have transformed the treatment landscape of oncogene-addicted non-small cell lung cancer (NSCLC), the influence of sex on treatment outcomes remains insufficiently understood., Objectives: This systematic review aimed to investigate the impact of sex on clinical outcomes in patients with NSCLC harboring driver fusions treated with targeted therapies enrolled in clinical trials., Data Sources and Methods: A comprehensive literature search was conducted using PubMed, Embase, and relevant conference abstracts to identify phase III randomized and early clinical trials that reported sex-specific data, including progression-free survival (PFS), overall survival (OS), overall response rate, and adverse events (AEs), in patients with fusion-positive NSCLC treated with tyrosine kinase inhibitors (TKIs)., Results: This review involved 10 studies reporting PFS data and 3 studies with OS data, focusing on first-line treatments for ALK fusion (9 studies) and RET fusion-positive (1 study) NSCLC. Pooled analysis of hazard ratios (HRs) for PFS and OS in ALK inhibitors trials revealed no significant differences in survival outcomes based on sex. Additionally, none of the studies provided data on sex-based differences in response rates or toxicities, highlighting a significant knowledge gap regarding the impact of sex on secondary outcomes in targeted therapy., Conclusion: This review found no significant sex-related differences in survival outcomes among patients treated with ALK inhibitors. However, the lack of data on sex-specific response and toxicity emphasizes the need for future research to better understand the role of sex in modulating treatment outcomes and treatment decisions with TKIs., Competing Interests: E.A.—Lectures and educational activities: MSD, Janssen; Consulting, Advisory role: from Amgen and Sanofi; Travel, Accommodations: Amgen, Ipsen. D.M.: Lectures and educational activities: Astellas Pharma, PharmaMar, Roche; Travel, Accommodations: Novartis, Lilly, Bristol-Myers Squibb, Merck. D.I.—Lectures and educational activities: Amgen, AstraZeneca, Bayer, BMS, Boehringer Ingelheim, F. Hoffmann-La Roche, Johnson & Johnson, Lilly, MSD, Pfizer, Pharmamar, Takeda; Consulting, advisory role: AbbVie, Amgen, AstraZeneca, Bayer, BMS, Beigene, Boehringer Ingelheim, F. Hoffmann-La Roche, Johnson & Johnson, Lilly, Merck, MSD, Pfizer, Pharmamar, Sanofi, Takeda; Clinical Trials: AbbVie, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, BMS, Daiichi Sankyo, F. Hoffmann-La Roche, GSK, Johnson & Johnson, Lilly, Merck, Mirati, MSD, Novartis, Pfizer, Pharmamar, Sanofi; Research Grants: AstraZeneca, BMS, F. Hoffmann-La Roche, GSK. G.L.R.—Consulting, advisory role: Merck Sharp and Dohme, Takeda, Amgen, Eli Lilly, BMS, F. Hoffmann-La Roche, Italfarmaco, Novartis, Sanofi, Pfizer, AstraZeneca. L.M.—Lectures and educational activities: Bristol-Myers Squibb, AstraZeneca, Roche, Takeda, Janssen, Pfizer, MSD, Radonova; Consulting, advisory role: Roche, Takeda, Janssen, MSD; Research Grants: Inivata, AstraZeneca, Gilead; Travel, Accommodations, Expenses: Bristol-Myers Squibb, Roche, Takeda, AstraZeneca, Janssen. All other authors declare no conflicts of interest., (© The Author(s), 2024.)

Introduction: Hotspots (HS) mutations in the PIK3CA gene may lead to poorer oncological outcomes and endocrine resistance in advanced breast cancer (BC), but their prognostic role in early-stage disease remains controversial. The overall agreement within plasma and tissue methods has not been well explored. Our aim was to correlate tissue and plasma approaches and to analyze the prognostic impact of PIK3CA mutations (PIK3CAm) in HR+/HER2- BC., Methods: A retrospective and unicentric analysis of PIK3CA mutational status in tissue and plasma samples by Cobas®PIK3CA Mutation Kit in patients with HR+/HER2- BC., Results: We analyzed 225 samples from 161 patients with luminal BC. PIK3CA mutations were identified in 62 patients (38.5%), of which 39.6% were found in tissue and 11.8% in plasma. In advanced disease, plasma and tissue correlation rate was performed in 64 cases, with an overall agreement of 70.3%. Eighty patients were treated with CDK4/6 inhibitors + endocrine therapy. We observed a moderately worse progression-free survival (PFS) in PIK3CAm versus wild-type (WT) (24 m vs. 30 m; HR = 1.39, p = 0.26). A subanalysis was carried out based on exons 9 and 20, which showed a statistically poorer PFS in PIK3CAm exon 9 versus 20 population (9.7 m vs. 30.3 m; HR = 2.84; p = 0.024). Furthermore, detection of PIK3CAm in plasma was linked to a worse PFS vs PIK3CAm detection just in tissue (12.4 vs. 29.3; HR = 2.4; p = 0.08)., Conclusions: Our findings suggest the PIK3CA evaluation in tissue as the diagnostic method of choice, however, additional investigations are required to improve the role of liquid biopsy in the PIK3CA assessment. PIK3CAm show worse outcomes in advanced luminal BC, especially in exon 9 mutation carriers, despite visceral involvement, prior exposure to endocrine therapy or detection of PIK3CAm in plasma, with an unclear prognosis in early-stage disease. Nonetheless, this should be validated in a prospective cohort study., (© 2024 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.)

We aim to improve knowledge on risk factors that relate to mortality in subjects with exacerbation of chronic obstructive pulmonary disease (COPD) who are hospitalized in General Medicine departments. In a cross-sectional multicenter study, by means of a logistic regression analysis, we assessed the possible association of death during hospitalization with the following groups of variables of participating patients: sociodemographic features, treatment received prior to admission and during hospitalization, COPD-related clinical features recorded prior to admission, comorbidity diagnosed prior to admission, clinical data recorded during hospitalization, laboratory results recorded during hospitalization, and electrocardiographic findings recorded during hospitalization. A total of 398 patients was included; 353 (88.7%) were male, and the median age of the patients was 75 years. Of these patients, 21 (5.3%) died during hospitalization. Only 270 (67.8%) received inhaled β(2) agonists during hospitalization, while 162 (40.7%) received angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers. The median of predicted FEV(1) prior to admission was 42%. A total of 350 patients (87.9%) had been diagnosed with two or more comorbid conditions prior to admission. An association was found between increased risk of death during hospitalization and the previous diagnoses of pneumonia, coronary heart disease, and stroke. In conclusion, comorbidity is an important contributor to mortality among patients hospitalized in General Medicine departments because of COPD exacerbation.

Introduction: Listeria monocytogenes is an unusual pathogenic agent in the general population, but is an important cause of bacteriemia and meningoencephalitis among newborns, pregnant women, the elderly population, and immunosuppressed patients. In rare cases, it has been described in joint prosthesis infections., Methods: A case description of prosthetic joint infection caused by Listeria in a 74-year-old man is presented. A systematic review of the literature (MEDLINE up to November 2007) was performed, and the reported cases are summarized., Results: Sixteen cases of prosthetic joint infection by L. monocytogenes have been reported, mainly in patients of advanced age (mean, 67.4 years; mode, 70 years) and immunosuppressed patients. Most cases were late infections., Conclusion: L. monocytogenes should be kept in mind as a pathogen involved in joint prosthesis infection, particularly among the elderly and immunosuppressed populations. Based on the literature review, parenteral ampicillin for at least 6 weeks is the treatment of choice. If possible, prosthesis removal should also be performed.