First-line immune-based combinations or sunitinib in favorable-risk metastatic renal cell carcinoma: a real-world retrospective comparison from the ARON-1 study.

Introduction: Renal cell carcinoma (RCC) is one of the most common types of urogenital cancer. The introduction of immune-based combinations, including dual immune-checkpoint inhibitors (ICI) or ICI plus tyrosine kinase inhibitors (TKIs), has radically changed the treatment landscape for metastatic RCC, showing varying efficacy across different prognostic groups based on the International Metastatic RCC Database Consortium (IMDC) criteria.

Materials And Methods: This retrospective multicenter study, part of the ARON-1 project, aimed to evaluate the outcomes of favorable-risk metastatic RCC patients treated with immune-based combinations or sunitinib.

Clinical Manifestations.

Background: Remote and unsupervised administration of neuropsychological tests may increase opportunities to understand cognition in everyday life compared to in-clinic assessments. The technological sophistication and widespread use of smartphones now allows this platform to be used for remote neuropsychological testing. However, it is important to ensure that the validity of neuropsychological tests extends to remote and unsupervised administration.

Resolution of Neuropsychiatric Adverse Events After Switching to a Doravirine-Based Regimen in the Open-Label Extensions of the DRIVE-AHEAD and DRIVE-FORWARD Trials.

Background: Neuropsychiatric adverse events (NPAEs) are associated with several antiretrovirals. Doravirine (DOR), a non-nucleoside reverse transcriptase inhibitor indicated for HIV-1 treatment, does not interact significantly with known neurotransmitter receptors in vitro. First-line therapy with DOR-based regimens resulted in significantly fewer NPAEs than efavirenz/emtricitabine/tenofovir disoproxil fumarate (EFV/FTC/TDF) and similar rates to those of ritonavir-boosted darunavir (DRV/r) with 2 nucleos(t)ide reverse transcriptase inhibitors (NRTIs) through Week 96 of the phase 3 DRIVE-AHEAD and DRIVE-FORWARD studies, respectively.

The spatially informed mFISHseq assay resolves biomarker discordance and predicts treatment response in breast cancer.

Current assays fail to address breast cancer's complex biology and accurately predict treatment response. On a retrospective cohort of 1082 female breast tissues, we develop and validate mFISHseq, which integrates multiplexed RNA fluorescent in situ hybridization with RNA-sequencing, guided by laser capture microdissection. This technique ensures tumor purity, unbiased whole transcriptome profiling, and explicitly quantifies intratumoral heterogeneity.

Deficiency in NPC2 results in disruption of mitochondria-late endosome/lysosomes contact sites and endo-lysosomal lipid dyshomeostasis.

Dysfunction of the endo-lysosomal intracellular Cholesterol transporter 2 protein (NPC2) leads to the onset of Niemann-Pick Disease Type C (NPC), a lysosomal storage disorder. Metabolic and homeostatic mechanisms are disrupted in lysosomal storage disorders (LSDs) hence we characterized a cellular model of NPC2 knock out, to assess alterations in organellar function and inter-organellar crosstalk between mitochondria and lysosomes. We performed characterization of lipid alterations and confirmed altered lysosomal morphology, but no overt changes in oxidative stress markers.

Targeting chromosomally unstable tumors with a selective KIF18A inhibitor.

Chromosome instability is a prevalent vulnerability of cancer cells that has yet to be fully exploited therapeutically. To identify genes uniquely essential to chromosomally unstable cells, we mined the Cancer Dependency Map for genes essential in tumor cells with high levels of copy number aberrations. We identify and validate KIF18A, a mitotic kinesin, as a vulnerability of chromosomally unstable cancer cells.

A sustainable and expedited 'One-Stop' prostate cancer diagnostic pathway to reduce environmental impact and enhance accessibility.

Objective: To assess the carbon footprint, accessibility, and diagnostic performance of an expedited 'One-Stop' prostate cancer (PCa) diagnostic pathway.

Materials And Methods: A total of 1083 consecutive patients undergoing magnetic resonance imaging (MRI) followed by transrectal ultrasound fusion-guided prostate biopsy (PBx) were identified from a prospective database. The patients were divided according to the diagnostic pathway: One-Stop, with MRI and same-day PBx (3 hours apart), or Standard, with MRI followed by a second visit for PBx.

Sexual health in women and sexual-gender-minority patients with cancer: A nationwide survey on healthcare professional awareness and attitude on behalf of MITO and AIRO-gynecology group.

Background: Compared to male patients, sexual health remains poorly studied in women and sexual gender minority (SGM) patients with cancers.

Material And Methods: An online survey was developed by a multidisciplinary team to assess the awareness and attitude of Italian oncological providers facing sexual health during or after cancer treatment. On behalf of the respective scientific committees, the questionnaire was sent to Multicenter Italian Trials in Ovarian cancer and gynecologic malignancies group (MITO) and to Italian Association of Radiation Oncology (AIRO) Group.

Incidence and Survival of Patients With Prostate Cancer in North-Rhine Westphalia, Germany.

Introduction: There is no organized prostate cancer screening in Germany. The aim of this study was to investigate the development of incidence and survival in patients with primary malignant tumors of the prostate in relation to changing recommendations of prostate-specific antigen (PSA) screening in guidelines.

Methods: Age-standardized incidence rates and 5-year relative survival (RS) (period approach) were calculated using data from the cancer registry North Rhine-Westphalia with the subset of the administrative district Münster respectively for the years 1992-2019.

Biomarkers reflecting disturbed gut barrier under treatment with TNF inhibitors in radiographic axial spondyloarthritis.

Objectives: The objective of this study is to investigate lipopolysaccharid-binding protein (LBP), zonulin and calprotectin as markers of bacterial translocation, disturbed gut barrier and intestinal inflammation in patients with radiographic axial spondyloarthritis (r-axSpA) during tumour necrosis factor inhibitor (TNFi) therapy and to analyze the association between disease activity, response to treatment and biomarker levels.

Methods: Patients with active r-axSpA of the German Spondyloarthritis Inception Cohort starting TNFi were compared with controls with chronic back pain. Serum levels of LBP, zonulin and calprotectin were measured at baseline and after 1 year of TNFi therapy.

Impaired coagulation parameters in early RA are restored by effective antirheumatic therapy: a prospective pilot study.

Objectives: To assess the effect of treatment on haemostatic parameters in patients with early rheumatoid arthritis (RA).

Methods: Patients with newly diagnosed RA started methotrexate and were randomised to additional conventional treatment, certolizumab pegol, abatacept or tocilizumab. Several biomarkers for haemostasis were analysed including parameters of the two global haemostatic assays-overall haemostatic potential (OHP) and endogenous thrombin potential (ETP), as well as single haemostatic factors-fibrinogen, prothrombin fragment 1+2 (F1+2), D-dimer, thrombin activatable fibrinolysis inhibitor (TAFI) and clot lysis time (CLT) in 24 patients at baseline, 12 and 24 weeks after the start of the treatment.

Spatial proteomics reveals sirtuin 1 to be a determinant of T-cell infiltration in human melanoma.

Background: The tumour microenvironment significantly influences the clinical response of patients to therapeutic immune checkpoint inhibition (ICI), but a comprehensive understanding of the underlying immune-regulatory proteome is still lacking.

Objectives: To decipher targetable biologic processes that determine tumour-infiltrating lymphocytes (TiLs) as a cellular equivalent of clinical response to ICI.

Methods: We mapped the spatial distribution of proteins in TiL-enriched vs.

TRACERx analysis identifies a role for FAT1 in regulating chromosomal instability and whole-genome doubling via Hippo signalling.

Chromosomal instability (CIN) is common in solid tumours and fuels evolutionary adaptation and poor prognosis by increasing intratumour heterogeneity. Systematic characterization of driver events in the TRACERx non-small-cell lung cancer (NSCLC) cohort identified that genetic alterations in six genes, including FAT1, result in homologous recombination (HR) repair deficiencies and CIN. Using orthogonal genetic and experimental approaches, we demonstrate that FAT1 alterations are positively selected before genome doubling and associated with HR deficiency.

AI allows pre-screening of FGFR3 mutational status using routine histology slides of muscle-invasive bladder cancer.

Pathogenic activating mutations in the fibroblast growth factor receptor 3 (FGFR3) drive disease maintenance and progression in urothelial cancer. 10-15% of muscle-invasive and metastatic urothelial cancer (MIBC/mUC) are FGFR3-mutant. Selective targeting of FGFR3 hotspot mutations with tyrosine kinase inhibitors (e.

Cancer-specific innate and adaptive immune rewiring drives resistance to PD-1 blockade in classic Hodgkin lymphoma.

Hodgkin Reed-Sternberg (HRS) cells of classic Hodgkin lymphoma (cHL), like many solid tumors, elicit ineffective immune responses. However, patients with cHL are highly responsive to PD-1 blockade, which largely depends on HRS cell-specific retention of MHC class II and implicates CD4 T cells and additional MHC class I-independent immune effectors. Here, we utilize single-cell RNA sequencing and spatial analysis to define shared circulating and microenvironmental features of the immune response to PD-1 blockade in cHL.

Phase 3 Study of Talazoparib Plus Enzalutamide Versus Placebo Plus Enzalutamide as First-Line Treatment in Patients With Metastatic Castration-Resistant Prostate Cancer: TALAPRO-2 Japanese Subgroup Analysis.

Background: In TALAPRO-2, the poly(ADP-ribose) polymerase inhibitor talazoparib plus the androgen receptor-signaling inhibitor enzalutamide improved radiographic progression-free survival (rPFS) versus placebo plus enzalutamide (hazard ratio [HR] = 0.63; 95% CI, 0.51-0.

Right ventricular stroke work index from echocardiography in patients with pulmonary arterial hypertension-the role in short-term follow-up assessment.

Aims: Right ventricular (RV) failure causes high mortality in patients with pulmonary arterial hypertension (PAH). RV stroke work index (RVSWi) poses as a potential predictor of outcome. We evaluated how RVSWi by echocardiography (ECHO) or right heart catheterization (RHC) is altered following PAH treatment and if RVSWi is an indicator of outcome in PAH.

Dynamics of affect modulation in neurodevelopmental disorders (DynAMoND) - study design of a prospective cohort study.

Background: Attention-deficit/hyperactivity disorder (ADHD) is a common neuro-developmental disorder that often persists into adulthood. Moreover, it is frequently accompanied by bipolar disorder (BD) as well as borderline personality disorder (BPD). It is unclear whether these disorders share underlying pathomechanisms, given that all three are characterized by alterations in affective states, either long or short-term.

Targeting molecular pathways to control immune checkpoint inhibitor toxicities.

Immune checkpoint inhibitors (ICIs) have transformed cancer treatment but are frequently associated with immune-related adverse events (irAEs). This article offers a novel synthesis of findings from both preclinical and clinical studies, focusing on the molecular mechanisms driving irAEs across diverse organ systems. It examines key immune cells, such as T cell subsets and myeloid cells, which are instrumental in irAE pathogenesis, alongside an in-depth analysis of cytokine signaling [interleukin (IL)-6, IL-17, IL-4), interferon γ (IFN-γ), IL-1β, tumor necrosis factor α (TNF-α)], integrin-mediated interactions [integrin subunits αITGA)4 and ITGB7], and microbiome-related factors that contribute to irAE pathology.

Comparative efficacy and safety of treatment regimens for Pneumocystis jirovecii pneumonia in people living with HIV - A systematic review and network meta-analysis of randomized controlled trials.

Background: Pneumocystis jirovecii pneumonia (PCP) is a serious opportunistic infection in people living with HIV (PWH) who have low CD4 counts. Despite its side effects, trimethoprim-sulfamethoxazole (TMP-SMX) is currently considered the primary treatment for PCP.

Objectives: To compare the efficacy (treatment-failure and mortality) and tolerability (treatment change) of PCP treatment-regimens with a frequentist network meta-analysis (NMA).

Isolating high-quality RNA for RNA-Seq from 10-year-old blood samples.

There is much interest in analysing RNA, particularly with RNA Sequencing, across both research and diagnostic domains. However, its inherent instability renders it susceptible to degradation. Given the imperative for RNA integrity in such applications, proper storage and biobanking of blood samples and successful subsequent RNA isolation is essential to guarantee optimal integrity for downstream analyses.

Development of a Sensitive and Reliable Meso Scale Discovery-Based Electrochemiluminescence Immunoassay to Quantify TDP-43 in Human Biofluids.

Transactive response DNA-binding protein of 43 kDa (TDP-43) is a major component of pathological inclusions in various neurodegenerative disorders, including amyotrophic lateral sclerosis and frontotemporal lobar degeneration. The detection of TDP-43 in biofluids is crucial for the development of diagnostic and prognostic indicators of disease and therapeutic development for TDP-43-related proteinopathies. Despite its potential as a biomarker for numerous neurological disorders, the lack of a sensitive and reproducible TDP-43 assay hinders progress in TDP-43-based therapy development, underscoring the need for an effective and standardized method for accurate quantification.