BackgroundGranulicatella adiacens is a fastidious Gram-positive coccus and is a rare but recognized cause of infective endocarditis. Infective endocarditis during pregnancy is uncommon but carries substantial maternal and fetal risk. Plasma metagenomic analysis of microbial cell-free DNA has emerged as a complementary diagnostic tool in culture-negative infections.Case SummaryWe describe a 35-year-old pregnant woman with known mitral valve prolapse who presented at 21 weeks of gestation with an acute ischemic stroke. Initial etiological work-up, including transesophageal echocardiography, was unremarkable. Ten days later, she re-presented with left-arm pain and neurologic symptoms. Repeat echocardiography revealed multiple mitral vegetations compatible with infective endocarditis. Despite multiple sets of prolonged-incubation blood cultures and extensive serological testing, all microbiological investigations remained negative. Empirical intravenous ceftriaxone was initiated based on the working diagnosis of HACEK endocarditis. A plasma metagenomic cell-free DNA test ultimately identified G. adiacens, which was suspected to have entered the body through dental treatment received a few weeks earlier. Ceftriaxone was continued given the favorable clinical response, with vegetation resolution, troponin decline, and uncomplicated term delivery of a healthy infant.ConclusionThis case illustrates the diagnostic challenges of culture-negative infective endocarditis in pregnancy and underscores the value of plasma microbial cell-free DNA sequencing as a complementary tool when conventional methods fail. It also emphasizes the need to repeat echocardiography when clinical suspicion remains high and raises the question of antibiotic prophylaxis for high-risk dental procedures in pregnant women with underlying valvular heart disease.
Immunotherapy has revolutionized the management of metastatic non-small cell lung cancer (NSCLC) without targetable alterations. Its use depends on histology, tumor PD-L1 expression, Performance Status (PS) score and patient age. The objective is to describe real-life therapeutic attitudes in France in 2020 and to analyze the adequacy with the professional standards applicable. The KBP-2020 study is a prospective observational study, including patients diagnosed de novo with primary lung cancer in 2020, followed in France in the participating non-university hospitals. Retrospective data analysis provides information on the first-line distribution of systemic treatments (immunotherapy, chemotherapy or the combination of both) in patients with stage IV NSCLC (542 squamous and 2082 non-squamous) without ALK rearrangement/alteration or EGFR mutations and PS score≤2. Immunotherapy alone or combined with chemotherapy is prescribed according to tumor PD-L1 expression: in case of PD-L1≥50%, in 85.2% of non-squamous and 86.6% of squamous patients, in case of PD-L1 [1-49%], in 61.7% of non-squamous and 45% of squamous patients and in case of PD-L1<1%, immunotherapy alone or combined with chemotherapy is prescribed in 56.48% of non-squamous and 30.86% of squamous patients. The use of immunotherapy in real life in 2020 in France shows an apparent gap with national guidelines that is more marked in cases of squamous cell NSCLC or with PD-L1 expression<50% with less exposure of patients to the immunotherapy-chemotherapy combination compared to current recommendations. This gap could be partly explained by the progressive reimbursement schedule of pembrolizumab and by other factors not documented in KBP-2020-CPHG.
PurposeCutaneous melanoma (CM) incidence is rising, and despite advances in immune checkpoint inhibitors (ICI), many metastatic patients do not respond or develop resistance. This study aimed to evaluate the prognostic value of a pre-treatment FDG-PET/CT-based radiomic model (MEL-RAD) for predicting 1-year progression-free survival (1y-PFS) in metastatic CM patients treated with first-line ICI.MethodsWe retrospectively included 154 metastatic CM patients from two centers who underwent pre-treatment FDG-PET/CT before ICI initiation. Patients were split into a development cohort (n=95) and an independent testing cohort (n=59). Radiomic features were extracted and harmonized to reduce inter-cohort variability. A two-step feature selection identified three key wavelet-transformed texture features used to build the MEL-RAD predictive model. The model’s performance was assessed by receiver operating characteristic (ROC) analysis, sensitivity, specificity, and predictive values. Survival analyses (progression-free (PFS) and overall survival (OS)) were performed with Cox regression and Kaplan-Meier methods.ResultsIn the development cohort, MEL-RAD achieved an AUC of 0.74 (p<0.0001) for predicting 1y-PFS. Using a 55% probability threshold, sensitivity was 93.8%, specificity 31.9%, with positive and negative predictive values of 58.4% and 83.4%, respectively. Patients with MEL-RAD >55% had significantly worse PFS (HR = 2.73, p=0.0009) and OS (HR = 3.20, p=0.0003). These results were externally validated: in the testing cohort, MEL-RAD positivity remained significantly associated with poorer PFS (HR = 2.73, p=0.047), and showed non-significant for OS.ConclusionThe MEL-RAD radiomic model based on pre-treatment FDG-PET/CT offers a non-invasive biomarker to stratify metastatic CM patients treated with immunotherapy.
Supportive care in cancer (SCC) has a key role in improving quality of life and outcomes for patients on their cancer journey. The aim of the study was to assess improvements in supportive care organization in France. A prospective, non-interventional (observational), multicentric, national, quantitative study was conducted in France in a two-part mirror survey of healthcare providers (HCPs) and patients with cancer. Participants were recruited using different channels and completed a digital questionnaire. The data was collected on the LimeSurvey software platform between 9 October and 6 December 2023. A total of 1259 HCPs and 2660 patients completed the survey. Most HCPs (87
SF3B1 is an essential and ubiquitous splicing factor that plays a pivotal role in the early steps of pre-mRNA splicing. Recurrent somatic missense mutations in SF3B1 are frequent in cancers, but no constitutional variant has been reported so far. We describe here a cohort of 26 individuals with neurodevelopmental disorders, harbouring SF3B1 constitutional heterozygous variants that appeared mostly de novo. Patients present with a global developmental delay, associated with variable neurological and facial dysmorphic traits. A dichotomy may emerge between patients harbouring predicted loss of function (n = 9) and missense variants (n = 17), the latter being associated with a more severe and syndromic phenotype, including heart and gastrointestinal anomalies. We focused on de novo SF3B1 missense variants, which were largely distinct from those reported in cancer. Functional complementation assays show that de novo SF3B1 missense variants did not cause a loss of function of the protein. Targeted and genome-wide analysis of RNA splicing reveal that they affect canonical and alternative splicing more moderately than somatic variants, and subtly modify the splicing of many transcripts. These findings place SF3B1 among the rare U2 snRNP components implicated in both cancer and neurodevelopmental disorders, highlighting its critical and multifaceted role in human disease. This study reports that de novo germline missense variants in SF3B1, distinct from the somatic variants frequently observed in cancer, cause a neurodevelopmental disorder and disrupt global RNA splicing.
