Olaparib plus Abiraterone for Metastatic Castration-resistant Prostate Cancer: Pharmacokinetics Data from the PROpel Trial.

PROpel (NCT03732820) was a positive phase 3 trial that demonstrated a clinically significant improvement in radiographic progression-free survival with olaparib plus abiraterone versus placebo plus abiraterone in first-line metastatic castration-resistant prostate cancer. For a subset of PROpel patients, steady-state concentrations of olaparib, abiraterone, and Δ-abiraterone were measured in blood samples collected before and at several time points after dose administration. The pharmacokinetics (PK) for each drug and metabolite were evaluated to determine whether any clinically relevant drug-drug interactions between olaparib and abiraterone occurred.

Five-year outcomes with first-line nivolumab plus ipilimumab with 2 cycles of chemotherapy versus 4 cycles of chemotherapy alone in patients with metastatic non-small cell lung cancer in the randomized CheckMate 9LA trial.

Background: We report 5-year efficacy and safety outcomes from CheckMate 9LA in patients with metastatic non-small cell lung cancer (mNSCLC) and exploratory analyses in key patient subgroups.

Methods: Adults with stage IV/recurrent NSCLC and no sensitizing EGFR/ALK alterations were randomized to receive nivolumab plus ipilimumab with chemotherapy (n = 361) or chemotherapy (n = 358). Outcomes were assessed in all randomized patients and subgroups.

Intraperitoneal Administration of 17-DMAG as an Effective Treatment against Infection in BALB/c Mice: A Preclinical Study.

Background: Leishmaniasis is a significant global public health issue that is caused by parasites from genus. With limited treatment options and rising drug resistance, there is a pressing need for new therapeutic approaches. Molecular chaperones, particularly Hsp90, play a crucial role in parasite biology and are emerging as promising targets for drug development.

Pharmacokinetics, Dose-Proportionality, and Tolerability of Intravenous Tanespimycin (17-AAG) in Single and Multiple Doses in Dogs: A Potential Novel Treatment for Canine Visceral Leishmaniasis.

In the New World, dogs are considered the main reservoir of visceral leishmaniasis (VL). Due to inefficacies in existing treatments and the lack of an efficient vaccine, dog culling is one of the main strategies used to control disease, making the development of new therapeutic interventions mandatory. We previously showed that Tanespimycin (17-AAG), a Hsp90 inhibitor, demonstrated potential for use in leishmaniasis treatment.

Carbapenemase-producing Enterobacterales strains causing infections in companion animals-Portugal.

Unlabelled: An increase in carbapenem-resistant human nosocomial strains is occurring in Europe, namely with the and genes. We determined the prevalence of carbapenemase-producing Enterobacterales clinical strains in companion animals in Portugal and characterized their mobile genetic elements. Susceptibility data of a consecutive collection of 977 Enterobacterales clinical strains from a Portuguese private veterinary diagnostic laboratory were evaluated (January-December 2020).

Four-year clinical update and treatment switching-adjusted outcomes with first-line nivolumab plus ipilimumab with chemotherapy for metastatic non-small cell lung cancer in the CheckMate 9LA randomized trial.

Background: In CheckMate 9LA, nivolumab plus ipilimumab with chemotherapy prolonged overall survival (OS) versus chemotherapy regardless of tumor PD-L1 expression or histology. We report updated efficacy and safety in all randomized patients with a minimum 4-year follow-up and an exploratory treatment-switching adjustment analysis in all treated patients who received chemotherapy and subsequent immunotherapy.

Methods: Adults with stage IV/recurrent non-small cell lung cancer (NSCLC), no sensitizing alterations, and ECOG performance status ≤1 were randomized 1:1 to nivolumab 360 mg every 3 weeks plus ipilimumab 1 mg/kg every 6 weeks with chemotherapy (two cycles) or chemotherapy (four cycles, with optional maintenance pemetrexed for the nonsquamous population).

Dissemination of bla-carrying IncX3-type plasmid among non-clonal Escherichia coli strains colonising a dog with a skin infection caused by a carbapenem-resistant Klebsiella pneumoniae, United Kingdom.

A successful outcome of a post-surgical wound infection management by a carbapenem-resistant Klebsiella pneumoniae is described in a dog. Four multidrug-resistant and carbapenem-resistant Escherichia coli strains belonging to ST410 (n = 1) and ST648 (n = 3) were isolated from faecal samples and nasal swabs of this dog at admission to a veterinary hospital in the United Kingdom, and one month after discharge. Whole-genome sequencing analysis suggests dissemination of a 46,161-bp IncX3 bla-carrying plasmid among E.

Elucidating the role played by bone marrow in visceral leishmaniasis.

Leishmaniasis is a widespread group of infectious diseases that significantly impact global health. Despite high prevalence, leishmaniasis often receives inadequate attention in the prioritization of measures targeting tropical diseases. The causative agents of leishmaniasis are protozoan parasites of the genus, which give rise to a diverse range of clinical manifestations, including cutaneous and visceral forms.

infection alters macrophage and dendritic cell migration in a three-dimensional environment.

Leishmaniasis results in a wide spectrum of clinical manifestations, ranging from skin lesions at the site of infection to disseminated lesions in internal organs, such as the spleen and liver. While the ability of -infected host cells to migrate may be important to lesion distribution and parasite dissemination, the underlying mechanisms and the accompanying role of host cells remain poorly understood. Previously published work has shown that infection inhibits macrophage migration in a 2-dimensional (2D) environment by altering actin dynamics and impairing the expression of proteins involved in plasma membrane-extracellular matrix interactions.

Longitudinal study of ESBL/AmpC-producing Enterobacterales strains sharing between cohabiting healthy companion animals and humans in Portugal and in the United Kingdom.

Extended-spectrum beta-lactamase (ESBL)- and plasmid-mediated cephalosporinase (AmpC)-producing Enterobacterales (ESBL/AmpC-E) are an increasing healthcare problem in both human and veterinary medicine. The aim of this study was to investigate the possible sharing of ESBL/AmpC-E strains between healthy companion animals and humans of the same household in Portugal (PT) and the United Kingdom (UK). In a prospective longitudinal study, between 2018 and 2020, faecal samples were collected from healthy dogs (n=90), cats (n=20) and their cohabiting humans (n=119) belonging to 41 PT and 44 UK households.

Leishmania amazonensis infection impairs VLA-4 clustering and adhesion complex assembly at the adhesion site of J774 cells.

Cutaneous leishmaniasis is an infectious disease that may lead to a single or multiple disseminated cutaneous lesions. The mechanisms involved in Leishmania dissemination to different areas of the skin and the internal organs remain poorly understood. Evidence shows that Very Late Antigen-4 (VLA-4)-dependent phagocyte adhesion is impaired by Leishmania infection, which may be related to the mechanisms of parasite dissemination.

First-line nivolumab plus ipilimumab with two cycles of chemotherapy versus chemotherapy alone (four cycles) in metastatic non-small cell lung cancer: CheckMate 9LA 2-year patient-reported outcomes.

Background: In CheckMate 9LA (NCT03215706), first-line nivolumab plus ipilimumab with chemotherapy (2 cycles) significantly improved overall survival versus chemotherapy (4 cycles) in patients with metastatic non-small cell lung cancer and no known sensitising epidermal growth factor receptor/anaplastic lymphoma kinase alterations. We present exploratory patient-reported outcomes (PROs; minimum follow-up, 2 years).

Methods: In patients (N = 719) randomised 1:1 to nivolumab plus ipilimumab with chemotherapy or chemotherapy alone, disease-related symptom burden and health-related quality of life were assessed using the Lung Cancer Symptom Scale (LCSS) and 3-level EQ-5D (EQ-5D-3L).

Conceptual model of a semi-arid coastal aquifer using hydrogeochemical seasonal variation and isotopic fingerprints in Tamoios, Rio de Janeiro, Brazil.

The present study focuses on the Tamoios aquifer (Rio de Janeiro State, Brazil), which is under pressure due to receiving a significant volume of urban runoff and sewage. The objective was based on a number of hydrogeochemical and isotope data to assess the aquifer functioning and establishing a conceptual model to evaluate the hydrogeochemical processes. The database consisted of groundwater samples (n = 20) and surface water samples (fluvial, lagoon, and seawater) (n = 4), analyzed for major and trace constituents plus O and H isotopes.

colistin resistance gene sharing between from cohabiting dogs and humans, Lisbon, Portugal, 2018 to 2020.

BackgroundThe emergence of colistin resistance is a One Health antimicrobial resistance challenge worldwide. The close contact between companion animals and humans creates opportunities for transmission and dissemination of colistin-resistant bacteria.AimTo detect potential animal reservoirs of colistin-resistant and investigate the possible sharing of these bacteria between dogs, cats and their cohabiting humans in the community in Lisbon, Portugal.

Abiraterone and Olaparib for Metastatic Castration-Resistant Prostate Cancer.

BACKGROUND: Preclinical studies and results of a phase 2 trial of abiraterone and olaparib suggest a combined antitumor effect when the poly(adenosine diphosphate[ADP]-ribose) polymerase inhibitor olaparib is combined with next-generation hormonal agent abiraterone to treat metastatic castration-resistant prostate cancer (mCRPC). METHODS: We conducted a double-blind, phase 3 trial of abiraterone and olaparib versus abiraterone and placebo in patients with mCRPC in the first-line setting. Patients were enrolled regardless of homologous recombination repair gene mutation (HRRm) status.

ESBL/AmpC-Producing Causing Urinary Tract Infections in Non-Related Companion Animals and Humans.

Urinary tract infections (UTI) caused by are frequently diagnosed in humans and companion animals. Extended-spectrum beta-lactamase (ESBL)- and cephalosporinase (AmpC)-producing are worldwide-disseminated and frequently multidrug-resistant, hence leading to treatment failure and public health concerns. This study aimed to characterize and compare ESBL/AmpC-producing strains causing community-acquired UTI in companion animals and non-related humans.

In Vitro Differentiation of Human Dendritic Cells and their Markers in Leishmania Infection.

Leishmaniasis comprises a collection of clinical manifestations associated with the infection of obligate intracellular protozoans, Leishmania. The life cycle of Leishmania parasites consists of two alternating life stages (amastigotes and promastigotes), during which parasites reside within either arthropod vectors or vertebrate hosts, respectively. Notably, the complex interactions between Leishmania parasites and several cells of the immune system largely influence the outcome of infection.

Defective in Lipophosphoglycan Biosynthesis Interferes With Activation of Human Neutrophils.

Visceral leishmaniasis (VL) is often associated with hematologic manifestations that may interfere with neutrophil response. Lipophosphoglycan (LPG) is a major molecule on the surface of promastigotes, which has been associated with several aspects of the parasite-vector-host interplay. Here, we investigated how LPG from (.

Companion Animals-An Overlooked and Misdiagnosed Reservoir of Carbapenem Resistance.

The dissemination of antimicrobial-resistance is a major global threat affecting both human and animal health. Carbapenems are human use β-lactams of last resort; thus. the dissemination of carbapenemase-producing (CP) bacteria creates severe limitations for the treatment of multidrug-resistant bacteria in hospitalized patients.