ctDNA Dynamics and Mechanisms of Acquired Resistance in Patients Treated with Osimertinib with or without Bevacizumab from the Randomized Phase II ETOP-BOOSTER Trial.

Purpose: The ETOP 10-16 BOOSTER study was a randomized phase II trial of osimertinib and bevacizumab therapy versus osimertinib therapy in patients with an acquired EGFR T790M mutation. The mechanisms of acquired resistance to osimertinib and bevacizumab have not been described previously.

Experimental Design: Next-generation sequencing (Guardant360) was conducted in serial plasma samples.

Durvalumab With or Without Tremelimumab in Combination With Chemotherapy in First-Line Metastatic NSCLC: Five-Year Overall Survival Outcomes From the Phase 3 POSEIDON Trial.

Introduction: The primary analysis (median follow-up 34.9 mo across all arms) of the phase 3 POSEIDON study revealed a statistically significant overall survival (OS) improvement with first-line tremelimumab plus durvalumab and chemotherapy (T+D+CT) versus CT in patients with EGFR and ALK wild-type metastatic NSCLC (mNSCLC). D+CT had a trend for OS improvement versus CT that did not reach statistical significance.

A longitudinal study assessing the impact of elexacaftor/tezacaftor/ivacaftor on gut transit and function in people with cystic fibrosis using magnetic resonance imaging (MRI).

Background: Gastrointestinal (GI) symptoms in cystic fibrosis (CF) are common and disruptive. The effect of cystic fibrosis transmembrane conductance regulator (CFTR) modulators on the GI tract is not fully understood. The aim was to use magnetic resonance imaging (MRI) to determine if elexacaftor/tezacaftor/ivacaftor (ETI) changed GI function and transit.

C-X-C Motif Chemokine Receptor 4-Directed Scintigraphy Using [Tc]Tc-Pentixatec in Primary Aldosteronism: A Proof-of-Concept Study.

C-X-C motif chemokine receptor 4 (CXCR4)-directed imaging has gained clinical interest in aiding clinical diagnostics in primary aldosteronism (PA). We retrospectively evaluated the feasibility of CXCR4-directed scintigraphy using the novel CXCR-4 ligand [Tc]Tc-pentixatec in patients with PA. Six patients (mean age ± SD, 49 ± 15 y) underwent CXCR4-directed scintigraphy (including planar imaging and SPECT/CT) 30, 120, and 240 min after injection of 435 ± 50 MBq of [Tc]Tc-pentixatec.

[Fontan associated liver disease].

Fontan surgery is vital for infants born with a single-ventricle heart. This intervention establishes a new blood flow circuit bypassing the single ventricle, thereby the separating pulmonary and systemic circulation to preserve single ventricular function. However, it carries risks of hepatic complications, collectively termed Fontan-associated liver disease (FALD), characterized by progressive hepatic congestion and fibrosis potentially leading to an equivalent of cirrhosis.

[Gastroesophageal reflux disease in 2024].

Gastroesophageal reflux disease is the most frequent gastroente-rological diagnosis, with a high prevalence of symptoms impacting patients' quality of life and causing high economic costs. It has a -complex pathophysiology that encompasses different mechanisms and an overlap with functional disorders that cause similar symptoms. Hence, an accurate diagnosis and phenotyping of patients is crucial to individualize therapy and limit health costs.

Cyclin-dependent kinase 4 drives cystic kidney disease in the absence of mTORC1 signaling activity.

Progression of cystic kidney disease has been linked to activation of the mTORC1 signaling pathway. Yet the utility of mTORC1 inhibitors to treat patients with polycystic kidney disease remains controversial despite promising preclinical data. To define the cell intrinsic role of mTORC1 for cyst development, the mTORC1 subunit gene Raptor was selectively inactivated in kidney tubular cells lacking cilia due to simultaneous deletion of the kinesin family member gene Kif3A.

Validation of the C-X-C chemokine receptor 3 (CXCR3) as a target for PET imaging of T cell activation.

Purpose: CXCR3 is expressed on activated T cells and plays a crucial role in T-cell recruitment to the tumor microenvironment (TME) during cell-based and immune checkpoint inhibitor (ICI) immunotherapy. This study utilized a Cu-labeled NOTA-α-CXCR3 antibody to assess CXCR3 expression in the TME and validate it as a potential T cell activation biomarker in vivo.

Procedures: CXCR3 cells infiltrating MC38 tumors (B57BL/6 mice, untreated and treated with αPD-1/αCTLA-4 ICI) were quantified using fluorescence microscopy and flow cytometry.

Tumour mutational burden: clinical utility, challenges and emerging improvements.

Tumour mutational burden (TMB), defined as the total number of somatic non-synonymous mutations present within the cancer genome, varies across and within cancer types. A first wave of retrospective and prospective research identified TMB as a predictive biomarker of response to immune-checkpoint inhibitors and culminated in the disease-agnostic approval of pembrolizumab for patients with TMB-high tumours based on data from the Keynote-158 trial. Although the applicability of outcomes from this trial to all cancer types and the optimal thresholds for TMB are yet to be ascertained, research into TMB is advancing along three principal avenues: enhancement of TMB assessments through rigorous quality control measures within the laboratory process, including the mitigation of confounding factors such as limited panel scope and low tumour purity; refinement of the traditional TMB framework through the incorporation of innovative concepts such as clonal, persistent or HLA-corrected TMB, tumour neoantigen load and mutational signatures; and integration of TMB with established and emerging biomarkers such as PD-L1 expression, microsatellite instability, immune gene expression profiles and the tumour immune contexture.

Impact of COVID-19 infection on lung function and nutritional status amongst individuals with cystic fibrosis: A global cohort study.

Background: Factors associated with severe COVID-19 infection have been identified; however, the impact of infection on longer-term outcomes is unclear. The objective of this study was to examine the impact of COVID-19 infection on the trajectory of lung function and nutritional status in people with cystic fibrosis (pwCF).

Methods: This is a retrospective global cohort study of pwCF who had confirmed COVID-19 infection diagnosed between January 1, 2020 and December 31, 2021.

Outcomes of definite vs probable/presumed cardiac sarcoidosis: a systematic review and meta-analysis.

Background: Diagnosing cardiac sarcoidosis (CS), which can be associated with arrhythmias and heart failure, remains challenging despite multiple advances over time. The 2014 Heart Rhythm Society (HRS) consensus statement recommends an endomyocardial biopsy (EMB) to establish a definite diagnosis of CS. In the absence of a positive EMB, a diagnosis of probable or presumed CS is made on the basis of clinical and imaging criteria.

Tertiary lymphoid structure-related immune infiltrates in NSCLC tumor lesions correlate with low tumor-reactivity of TIL products.

Adoptive transfer of tumor infiltrating lymphocytes (TIL therapy) has proven highly effective for treating solid cancers, including non-small cell lung cancer (NSCLC). However, not all patients benefit from this therapy for yet unknown reasons. Defining markers that correlate with high tumor-reactivity of the autologous TIL products is thus key for achieving better tailored immunotherapies.

Prognostic value of the 5-SENSE Score to predict focality of the seizure-onset zone as assessed by stereoelectroencephalography: a prospective international multicentre validation study.

Introduction: Epilepsy surgery is the only curative treatment for patients with drug-resistant focal epilepsy. Stereoelectroencephalography (SEEG) is the gold standard to delineate the seizure-onset zone (SOZ). However, up to 40% of patients are subsequently not operated as no focal non-eloquent SOZ can be identified.

[Artificial intelligence in emergency radiology: fiction or reality?].

Artificial intelligence (AI) is a rapidly advancing technology in our society. The emergency radiology is an area facing an increase of the number of imaging studies and associated to the necessity to promptly deliver an accurate interpretation. The integration of AI algorithms to assist the clinician in providing analyses of the imaging studies while maintaining adequate diagnostic quality opens up new perspectives.