Background: Breast cancer in very young women (BCVY) defined as <35 years old, presents with different molecular biology than in older patients. High HDAC5 expression has been associated with poor prognosis in breast cancer (BC) tissue. We aimed to analyze HDAC5 expression in BCVY and older patients and their correlation with clinical features, also studying the potential of HDAC5 inhibition in BC cell lines. Methods: HDAC5 expression in 60 BCVY and 47 older cases were analyzed by qRT-PCR and correlated with clinical data. The effect of the HDAC5 inhibitor, LMK-235, was analyzed in BC cell lines from older and young patients. We performed time and dose dependence viability, migration, proliferation, and apoptosis assays. Results: Our results correlate higher HDAC5 expression with worse prognosis in BCVY. However, we observed no differences between HDAC5 expression and pathological features. Our results showed greatly reduced progression in BCVY cell lines and also in all triple negative subtypes when cell lines were treated with LMK-235. Conclusions: In BCVY, we found higher expression of HDAC5. Overexpression of HDAC5 in BCVY correlates with lower survival rates. LMK-235 could be a potential treatment in BCVY.

In recent years, many population pharmacokinetic (popPK) models have been developed for echinocandins to better understand the pharmacokinetics (PK) of these antifungals. This comprehensive review aimed to summarize popPK models of echinocandins (micafungin, caspofungin, anidulafungin, and rezafungin), by focusing on dosage optimization to maximize the probability of attaining the PK/PD target proposed in special populations. A search in PubMed, Embase, Web of Science, and Scopus, supplemented by the bibliography of relevant articles, was conducted from inception to March 2024, including both observational and prospective trials. A total of 1126 articles were identified, 47 of them were included in the review (22 for micafungin, 13 for caspofungin, 9 for anidulafungin, and 3 for rezafungin). A two-compartment model was more frequently used to describe the PK parameters of echinocandin (78.7% of developed models), although more complex structural models with three and four compartments have also been developed. The covariates to estimate the PK parameters such as clearance (CL) and volume of distribution (V_d) differed between models. Weight total (WT) was the most frequently reported to be a significant predictor for both parameters, especially for estimating the CL in pediatrics. The PD parameter most widely reported assessing the drug exposure–efficacy relationship was the area under the concentration–time curve to minimum inhibitory concentration (MIC) ratio (AUC_0–24/MIC) with different targets proposed for each echinocandin. In certain populations such as patients that are critically ill, obese, receiving extracorporeal membrane oxygenation (ECMO) and/or continuous renal replacement therapy (CRRT), or pediatric patients and/or patients with cancer or that are immunocompromised, the fixed dosing strategies recommended in the drug prescribing information may not reach the PK/PD target. For these populations, different strategies have been proposed, such as a dosing regimen based on body weight or increasing the loading and/or maintenance dose. Despite echinocandins’ favorable safety profile and predictable PK, certain groups at risk of suboptimal drug exposure can benefit from therapeutic drug monitoring (TDM) to prevent clinical failures. Numerous popPK models of echinocandins have been developed. However, an external validation of the suggested dosing regimens in conjunction with an analysis of population subgroups should be conducted before implementing a popPK model in clinical practice.

Introduction Real-life data about cefiderocol use to treat extensively drug-resistant bacteria are scarce. We aim to report our early experience in patients with difficult-to-treat infections and limited therapeutic options. Methods Patients treated with cefiderocol from March 2018 to April 2022 in a tertiary-care hospital in Spain were included. Demographic, clinical, and microbiological data were collected up to 90 days after the end of treatment or until death. Survival status was recorded at 30 and 90 days. Results Ten patients were included, seven of them critically ill. Ventilator-associated pneumonia (40%) and bacteremia (40%) were the main infections. Multidrug-resistant or extensively drug-resistant P. aeruginosa was the most frequently isolated pathogen (70%, of which six patients were infected with bacteria with difficult-to-treat resistance), followed by A. baumannii, E. coli, and A. xylosoxidans (10% each). Seven patients received combination therapy. Clinical and microbiological cures were achieved in 90% and 80% of patients, respectively. Two previously susceptible strains (20%) developed resistance to cefiderocol. Overall, 30-day and 90-day mortality rates were 10% and 50%, respectively, although two out of five patients died due to the infection. No serious adverse events were reported, except for one patient who developed thrombocytopenia. Conclusion Cefiderocol seems to be an effective and safe rescue therapy for patients infected with difficult-to-treat pathogens, although there is a definite risk of the emergence of resistance.

Population pharmacokinetic (popPK) models are an essential tool when implementing therapeutic drug monitoring (TDM) and to overcome dosing challenges in ne

Purpose: Sex influences chemotherapy-induced nausea and vomiting (CINV). However, in clinical practice, males and females receive the same antiemetic prophylaxis. We compared CINV between sexes in patients with different emetic risk schemes and evaluated the predisposing factors and main adverse effects caused by antiemetics. Methods: Prospective observational study conducted in a tertiary-care hospital from February 2023 to May 2024 in patients starting chemotherapy or a new treatment line. CINV was evaluated using MASCC antiemetic tool, in acute (< 24 h) and delayed phases (24–120 h). Results were analyzed using χ ² test or Fisher’s exact test. The primary endpoint was complete response (CR) rate, defined as no CINV and no use of rescue medication. Univariate and multivariate logistic regressions were used to identify patient-related risk factors associated with non-CR. Results: A total of 176 completed questionnaires (CQ): 94 for males and 82 for females were collected. The proportion of males who remained emesis-free was superior to females in the acute phase (100% versus 92.7%, p = 0.009). Likewise, a higher proportion of males remained nausea-free in the acute (91.5% versus 79.3%, p = 0.021) and delayed phase (90.4% versus 79.3%, p = 0.037). In females, young age (< 60 years) and previous nausea and vomiting during pregnancy may contribute to non-CR. A high proportion of patients reported adverse events like constipation and insomnia. Females suffered more constipation than males (52.4% versus 37.2%, p = 0.043). Conclusion: Females experienced more CINV than males, with the consequences that entail. Antiemetic prophylaxis should be personalized, considering sex and age and not only the chemotherapy emetic potential.