Challenges in multinational rare disease clinical studies during COVID-19: regulatory assessment of cipaglucosidase alfa plus miglustat in adults with late-onset Pompe disease.

PROPEL (ATB200-03; NCT03729362) compared the efficacy and safety of cipaglucosidase alfa plus miglustat (cipa + mig), a two-component therapy for late-onset Pompe disease (LOPD), versus alglucosidase alfa plus placebo (alg + pbo). The primary endpoint was change in 6-min walk distance (6MWD) from baseline to week 52. During PROPEL, COVID-19 interrupted some planned study visits and assessment windows, leading to delayed visits, make-up assessments for patients who missed ≥ 3 successive infusions before planned assessments at weeks 38 and 52, and some advanced visits (end-of-study/early-termination visits).

Neoadjuvant anti-PD-1 alone or in combination with anti-TIGIT or an oncolytic virus in resectable stage IIIB-D melanoma: a phase 1/2 trial.

Neoadjuvant immunotherapies have shown antitumor activity in melanoma. Substudy 02C of the global, rolling-arm, phase 1/2, adaptive-design KEYMAKER-U02 trial is evaluating neoadjuvant pembrolizumab (anti-PD-1) alone or in combination, followed by adjuvant pembrolizumab, for stage IIIB-D melanoma. Here we report results from the first three arms: pembrolizumab plus vibostolimab (anti-TIGIT), pembrolizumab plus gebasaxturev (coxsackievirus A21) and pembrolizumab monotherapy.

Contribution of Magnetic Resonance Imaging Studies to the Understanding of Cerebral Malaria Pathogenesis.

Cerebral malaria (CM), the most lethal clinical syndrome of infection, mostly affects children under 5 in sub-Saharan Africa. CM is characterized by seizures and impaired consciousness that lead to death in 15-20% of cases if treated quickly, but it is completely fatal when untreated. Brain magnetic resonance imaging (MRI) is an invaluable source of information on the pathophysiology of brain damage, but, due to limited access to scanners in endemic regions, only until very recently have case reports of CM patients studied with advanced MRI methods been published.

Risk Factors and Pain Management in the Incidence of Postoperative Delirium in Elderly Patients: A Retrospective Study.

: Postoperative delirium (POD) is a common surgical complication that increases hospital stay duration, hospitalization costs, readmission rates and mortality. This study aims to describe the incidence of POD in an elderly patient population and to investigate pain assessment as a risk factor for postoperative confusion. Additionally, we aim to determine a predictive model for POD.

Impact of Face Mask-Wearing on Quality of Life in Post-Surgical Oral Cancer Patients: A Cross-Sectional Study.

Treatments for oral squamous cell carcinomas (OSCCs) often result in significant aesthetic and functional issues, impacting patients' quality of life (QoL). The COVID-19 pandemic's mask mandates may have provided psychosocial benefits by concealing facial disfigurements, potentially reducing stigma. This study aimed to assess the impact of mask-wearing on the QoL of patients surgically treated for OSCC.

Metabolic adaptation of myeloid cells in the glioblastoma microenvironment.

In recent decades, immunometabolism in cancers has emerged as an interesting target for treatment development. Indeed, the tumor microenvironment (TME) unique characteristics such as hypoxia and limitation of nutrients availability lead to a switch in metabolic pathways in both tumor and TME cells in order to support their adaptation and grow. Glioblastoma (GBM), the most frequent and aggressive primary brain tumor in adults, has been extensively studied in multiple aspects regarding its immune population, but research focused on immunometabolism remains limited.

Pulmonary Consequences of Surgical Treatment in Children's Primary Lung Tumors: A National Retrospective Study.

Background And Aims: Primary lung tumors (PLTs) in children are rare, and surgery remains the key to ensure remission. Here we describe the PLTs clinical characteristics, their management, and the pulmonary outcome following surgery.

Methods: We carried out a French national cohort of pediatric PLTs from 2013 to 2023 from the FRACTURE rare pediatric tumors national database.

Joint EANM/EANO/RANO/SNMMI practice guideline/procedure standard for PET imaging of brain metastases: version 1.0.

This joint practice guideline/procedure standard was collaboratively developed by the European Association of Nuclear Medicine (EANM), the Society of Nuclear Medicine and Molecular Imaging (SNMMI), the European Association of Neuro-Oncology (EANO), and the PET task force of the Response Assessment in Neurooncology Working Group (PET/RANO). Brain metastases are the most common malignant central nervous system (CNS) tumors. PET imaging with radiolabeled amino acids and to lesser extent [F]FDG has gained considerable importance in the assessment of brain metastases, especially for the differential diagnosis between recurrent metastases and treatment-related changes which remains a limitation using conventional MRI.

Physiologically Based Pharmacokinetic Model of Cefotaxime in Patients with Impaired Renal Function.

Background: Cefotaxime is a widely prescribed cephalosporin antibiotic used to treat various infections. It is mainly eliminated unchanged by the kidney through tubular secretion and glomerular filtration. Therefore, a reduction of kidney function may increase exposure to the drug and induce toxic side effects.

Amivantamab Plus Lazertinib in Patients With EGFR-mutant Non-small Cell Lung Cancer (NSCLC) After Progression on Osimertinib and Platinum-based Chemotherapy: Results From CHRYSALIS-2 Cohort A.

Introduction: Treatment options for patients with epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC) with disease progression on/after osimertinib and platinum-based chemotherapy are limited.

Methods: CHRYSALIS-2 Cohort A evaluated amivantamab+lazertinib in patients with EGFR exon 19 deletion- or L858R-mutated NSCLC with disease progression on/after osimertinib and platinum-based chemotherapy. Primary endpoint was investigator-assessed objective response rate (ORR).

Profile and Usefulness of Serum Cytokines to Predict Prognosis in Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease.

Objectives: To characterize the serum cytokine profile in myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) at onset and during follow-up and assess their utility for predicting relapses and disability.

Methods: This retrospective multicentric cohort study included patients aged 16 years and older meeting MOGAD 2023 criteria, with serum samples collected at baseline (≤3 months from disease onset) and follow-up (≥6 months from the baseline), and age-matched and time to sampling-matched patients with multiple sclerosis (MS). Eleven cytokines were assessed using the ELLA system.

Anticipatory smooth pursuit eye movements scale with the probability of visual motion: The role of target speed and acceleration.

Sensory-motor systems can extract statistical regularities in dynamic uncertain environments, enabling quicker responses and anticipatory behavior for expected events. Anticipatory smooth pursuit eye movements (aSP) have been observed in primates when the temporal and kinematic properties of a forthcoming visual moving target are fully or partially predictable. To investigate the nature of the internal model of target kinematics underlying aSP, we tested the effect of varying the target kinematics and its predictability.

Body mass index affects imatinib exposure: Real-world evidence from TDM with adaptive dosing.

Background: Imatinib is the treatment of elderly or frail patients with chronic myeloid leukemia (CML). Trough levels of around 1000 ng/ml are considered as the target exposure.

Objectives: We searched for baseline parameters associated with imatinib pharmacokinetics, and studied the clinical impact of subsequent adaptive dosing.

FLI1 and GATA1 govern transcription: new insights into FLI1-related platelet disorders.

Germline variants of FLI1, essential for megakaryopoiesis, are linked to bleeding disorders, platelet aggregation defects and mild thrombocytopenia. However, the mechanisms behind these abnormalities remain unclear. This study aims to elucidate the impact of FLI1 variants on human megakaryocytes and platelets.

Tatton-Brown-Rahman syndrome: A new multiple endocrine neoplasia syndrome with intellectual disability?

We describe for the first time the case of a woman presenting with Tatton-Brown-Rahman syndrome (TBRS) and multiple endocrine neoplasia (MEN). She developed primary hyperparathyroidism at age 13, a pituitary cyst at age 14, adrenal tumor at age 21, and metastatic insulinoma at age 34. In addition, she showed intellectual disability, obesity, multiple lipomas, facial dysmorphia, hemihypertrophy and kyphoscoliosis.

Real-world multicentre cohort study on choices and effectiveness of immunotherapies in NMOSD and MOGAD.

Background: Recurrent attacks in neuromyelitis optica spectrum disorders (NMOSDs) or myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) can lead to severe disability. We aimed to analyse the real-world use of immunotherapies in patients with NMOSD and MOGAD, focusing on changes in treatment strategies, effects on attack rates (ARR) and risk factors for attacks.

Methods: This longitudinal registry-based cohort study included 493 patients (320 with aquaporin-4 immunoglobulin G (AQP4-IgG) seropositive NMOSD (65%), 44 with AQP4-IgG seronegative NMOSD (9%) and 129 MOGAD (26%)) with 1247 treatments from 19 German and one Austrian centre from the registry of the neuromyelitis optica study group (NEMOS).

SMCHD1 genetic variants in type 2 facioscapulohumeral dystrophy and challenges in predicting pathogenicity and disease penetrance.

The molecular diagnosis of type 1 facioscapulohumeral muscular dystrophy (FSHD1) relies on the detection of a shortened D4Z4 array at the 4q35 locus. Until recently, the diagnosis of FSHD2 relied solely on the absence of a shortened D4Z4 allele in clinically affected patients. It is now established that most FSHD2 cases carry a heterozygous variant in the SMCHD1 gene.

Role of viruses in periodontitis: An extensive review of herpesviruses, human immunodeficiency virus, coronavirus-19, papillomavirus and hepatitis viruses.

Periodontitis is the inflammation of the supporting structures around the dentition. Several microbial agents, mostly bacteria, have been identified as causative factors for periodontal disease. On the other hand, oral cavity is a rich reservoir for viruses since it contains a wide variety of cell types that can be targeted by viruses.

Mechanistic Learning for Predicting Survival Outcomes in Head and Neck Squamous Cell Carcinoma.

We employed a mechanistic learning approach, integrating on-treatment tumor kinetics (TK) modeling with various machine learning (ML) models to address the challenge of predicting post-progression survival (PPS)-the duration from the time of documented disease progression to death-and overall survival (OS) in Head and Neck Squamous Cell Carcinoma (HNSCC). We compared the predictive power of model-derived TK parameters versus RECIST and assessed the efficacy of nine TK-OS ML models against conventional survival models. Data from 526 advanced HNSCC patients treated with chemotherapy and cetuximab in the TPExtreme trial were analyzed using a double-exponential model.

A French Multicenter Real-Life Study on the Biological and Clinical Parameters Associated With Response to Immune Checkpoint Inhibitors (ICIs) in Second-Line Treatment of Advanced Urothelial Carcinoma: Impact of Antibiotics Administration at the Time of ICIs Initiation.

Background: After failure of first-line chemotherapy, standard of care for advanced urothelial cancer (aUC) is immune checkpoint inhibitors (ICIs) targeting PD-1/PD-L1 pathway. Several prognostic models (Bajorin and Bellmunt scores) have been evaluated, but only in the context of chemotherapy.

Objective: To study whether the variables in these scores and new emerging clinical and biological criteria have an impact on the probability of objective response in aUC treated with ICIs in 2nd-line setting and beyond.

Effect of oral nintedanib vs placebo on epistaxis in hereditary hemorrhagic telangiectasia: the EPICURE multicenter randomized double-blind trial.

Epistaxis greatly affects patients with hereditary hemorrhagic telangiectasia (HHT). Although few systemic treatment exist, nintedanib, is a good candidate thanks to its anti-angiogenic activity. Our main objective was to evaluate the efficacy of oral nintedanib on epistaxis duration in HHT patients with moderate to severe epistaxis.

When to stop immunotherapy for advanced melanoma: the emulated target trials.

Background: Immune checkpoint inhibitors (ICIs) have demonstrated their efficacy with a 7.5-year overall survival (OS) close to 50% for advanced stages. The design of clinical trials provides for treatment until progression or toxicity, or for a maximum duration of two years.

Detection of antibodies to infliximab in routine care: a 4-year French retrospective study.

Despite its wide use to treat various inflammatory diseases, infliximab becomes ineffective in some patients due to inadequate drug levels and production of anti-drug antibodies (ADA). The aim of this study was to compare the prevalence and ADA levels in a large cohort of patients. ADA and infliximab (IFX) through levels measured by enzyme-linked immunosorbent assay were collected from 505 patients within a period of 4 years.

What's new in the pediatric spine?

Introduction: The field of pediatric spine surgery has encountered major changes and evolutions lately, with new treatment options available and the development of enabling technologies. This article aims to summarize the most relevant recent literature.

Materials And Methods: The five most relevant topics were selected and assigned to one or two authors who performed a comprehensive Pubmed database search for articles published in the last 4 years (2021-2024).