How to facilitate the wider use of pharmacogenetic tests?

4P medicine (personalized, preventive, predictive, and participatory) is experiencing a remarkable rise, and pharmacogenetics is an essential part of it. However, several obstacles are hindering its deployment. This round table brought together a group of experts to take stock of the situation, reflecting on ways to facilitate the prescription of these tests and the dissemination of the results on a national scale.

Loudness of snoring, not apnea-hypopnea index, is associated with hyperactivity behavior in snoring children and adolescents.

Study Objectives: It is unknown whether loudness of snoring or hypoxic burden are related to higher hyperactivity scores in habitually snoring children and whether this effect is impacted by the severity of sleep-disordered breathing (SDB). This study investigates the prevalence of hyperactivity in children with habitual snoring and the independent effects of loudness of snoring, as reported by the parents, hypoxic burden and obstructive sleep apnea syndrome's severity (OSAS) on hyperactivity, as measured by the Conners' Parent Rating Scale-Hyperactivity Index (CPRS-HI).

Methods: Children with habitual snoring aged 3-18 years were recruited for an overnight polysomnography reporting apnea-hypopnea index (AHI) and hypoxic burden, acoustic rhinometry, clinical examination and parental questionnaires assessing snoring loudness and CPRS-HI.

Efficacy of a vein visualisation device for facilitating peripheral venous line placement in adult patients with sickle cell disease: A randomised clinical trial.

Background: Intravenous (IV) access is often required for the treatment of vaso-occlusive crises in patients with sickle cell disease, but can be particularly challenging due to recurrent venous damage. The AccuVein® device, uses near-infrared light technology to visualise veins for easier venepuncture.

Methods: A randomised, controlled trial of the efficacy of the AccuVeinAV400® device in the replacement of peripheral venous lines during a vaso-occlusive crisis was conducted at two centres in France.

Microsporidiosis in Patients with Autoimmune Diseases Undergoing Monoclonal Antibody Associated Therapy.

We present Enterocytozoon bieneusi infection in four patients with autoimmune diseases undergoing prolonged monoclonal antibody therapies. Two patients suffered from inflammatory bowel disease and received anti-TNF therapies, whereas two other patients suffered from systemic lupus erythematosus with renal involvement and received anti-CD20 or anti-BLyS protein therapies. Three out of four patients consulted for diarrhea with abdominal pain without intestinal inflammation or bleeding at the time of sampling.

Major role of dolutegravir in the emergence of the S147G integrase resistance mutation.

Background: The S147G mutation is associated with high-level resistance to the integrase strand transfer inhibitor (INSTI) elvitegravir. In several poorly documented cases, it was also selected in patients on dolutegravir. Given the widespread use of dolutegravir, further studies of S147G are required.

Biomarkers.

Background: Increasing evidence supports the use of plasma biomarkers of amyloid, tau, neurodegeneration and neuroinflammation for diagnosis of dementia. However, their performance for positive and differential diagnosis of dementia with Lewy bodies (DLB) in clinical settings is still uncertain.

Method: We conducted a retrospective biomarker study in two tertiary memory centers, Paris Lariboisière and CM2RR Strasbourg, France, enrolling patients with DLB (n=104), Alzheimer's disease (AD, n=76) and neurological controls (NC, n=27).

Biomarkers.

Background: The identification of biomarkers for Alzheimer's disease (AD) remains a significant challenge, particularly for the clinical severity of the disease. Recent studies have shown that plasma brain-derived-tau (BD-Tau) could be a promising biomarker for the identification of AD-type neurodegeneration. This study aimed to investigate the potential of BD-Tau in differentiating various clinical stages of AD, ranging from cognitively unimpaired AD to severe dementia AD.

T cell malignancies after CAR T cell therapy in the DESCAR-T registry.

The risk of T cell malignancies after chimeric antigen receptor (CAR) T cell therapy is a concern, although the true incidence remains unclear. Here we analyzed the DESCAR-T registry database, encompassing all pediatric and adult patients with hematologic malignancies who received CAR T cell therapy in France since 1 July 2018. Of the 3,066 patients included (2,536 B cell lymphoma, 162 B cell acute lymphoblastic leukemia (ALL) and 368 multiple myeloma), 1,680 (54.

SLC10A7 regulates O-GalNAc glycosylation and Ca homeostasis in the secretory pathway: insights into SLC10A7-CDG.

Glycans are known to be fundamental for many cellular and physiological functions. Congenital disorders of glycosylation (CDG) currently encompassing over 160 subtypes, are characterized by glycan synthesis and/or processing defects. Despite the increasing number of CDG patients, therapeutic options remain very limited as our knowledge on glycan synthesis is fragmented.

Benefit and Harms of Radical Nephroureterectomy as Part of a Multimodal Treatment Strategy for Upper Tract Urothelial Carcinoma Patients Presenting with Clinical Evidence of Regional Lymph Node Metastasis: A Systematic Review and Meta-analysis by the European Association of Urology Guidelines.

Background And Objective: Given the uncertainty regarding the role of radical nephroureterectomy (RNU) as part of a multimodal treatment strategy for upper tract urothelial carcinoma (UTUC) patients with cN+ disease, we aimed to perform a systematic review and meta-analysis of the corresponding literature.

Methods: Using the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines, we identified 17 observational comparative and noncomparative studies, published between January 2000 and September 2024, evaluating UTUC patients with cTanyN+M0 disease (P) who received RNU as part of a multimodal treatment strategy (I), as compared with any treatment strategy if applicable (C), to assess oncological or postoperative outcomes (O). Meta-analyses were further performed, as appropriate.

Prognosis Associated with Complete Pathological Response Following Neoadjuvant Treatment for PancreaTic AdenOcarciNOma in the FOFLIRINOX Era: the Multicenter TONO Study.

Background: The use of multiagent FOLFIRINOX chemotherapy for pancreatic adenocarcinoma in a neoadjuvant setting has been associated with an increased rate of complete pathological response (CPR) after surgery. This study investigated the long-term outcomes of patients with CPR in a multicenter setting to identify prognostic factors for overall survival (OS) and recurrence-free survival (RFS).

Methods: This retrospective cohort study examined biopsy-proven pancreatic adenocarcinomas with CPR after neoadjuvant chemotherapy or chemoradiotherapy and surgery, between January 2006 and December 2023 across 22 French and  2 Belgian centers.

Use of a trigger tool to describe and screen drug-related hospital admissions in older adults: the TRIGGAge retrospective cohort study.

Introduction: Drug-related hospital admissions (DRAs) can account for 5%-40% of total hospital admissions in older adults, with a significant proportion deemed preventable. To increase the detection of DRAs, in 2021, a revised trigger tool listing 21 frequent causes of admissions and medications at risk was proposed. This study aimed to describe DRAs using this trigger tool in a French acute geriatric ward and to assess the performance of the tool.

Asciminib resistance of a new BCR::ABL1 p.I293_K294insSSLRD mutant detected in a Ph + ALL patient.

Chronic myeloid leukemia and Philadelphia chromosome-positive acute lymphoblastic leukemia patients largely benefit from an expanding tyrosine kinase inhibitors (TKIs) toolbox that has improved the outcome of both diseases. However, TKI success is continuously challenged by mutation-driven acquired resistance and therefore, close monitoring of clonal genetic diversity is necessary to ensure proper clinical management and adequate response to treatment. Here, we report the case of a ponatinib-resistant Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph + ALL) patient harboring a BCR::ABL1 p.

Prognostic Value of Cardiac MRI Late Gadolinium Enhancement Granularity in Participants with Ischemic Cardiomyopathy.

Background Ischemic late gadolinium enhancement (LGE) assessed with cardiac MRI is a well-established prognosticator in ischemic cardiomyopathy. However, the prognostic value of additional LGE parameters, such as extent, transmurality, location, and associated midwall LGE, remains unclear. Purpose To assess the prognostic value of ischemic LGE features to predict all-cause mortality in ischemic cardiomyopathy.

Reintervention for Acute Aortic Prosthesis Endocarditis: Early and Mid-Term Outcomes.

This study aimed to analyze the outcomes and challenges associated with surgical redo procedures following aortic valve replacement for acute infective endocarditis. While transcatheter aortic valve implantation is growing in terms of its utilization for degenerative bioprostheses failure, valve-in-valve procedures are limited in acute aortic endocarditis. Surgical interventions for aortic prosthesis endocarditis carry a significant risk, with a higher mortality and morbidity, often requiring concomitant complex procedures.

Paediatric-to-adult transition in type 1 diabetes: A two-centre experience of a structured program, 2014 to 2022.

Background: Transition from paediatric to adult healthcare is a turning point for patients with Type 1 diabetes (T1D). A gradual coordinated process connecting paediatric and adult healthcare providers may improve adherence to adult follow-up.

Aims: To describe a transition process developed jointly by paediatric and adult diabetology units and compare patients progressing or not to follow-up in adult care setting.

Association between cerebral oxygenation and usual parameters of cerebral perfusion in critically ill patients with acute brain injury.

In patients with acute brain injury (ABI), optimizing cerebral perfusion parameters relies on multimodal monitoring. This include data from systemic monitoring-mean arterial pressure (MAP), arterial carbon dioxide tension (PaCO), arterial oxygen saturation (SaO), hemoglobin levels (Hb), and temperature-as well as neurological monitoring-intracranial pressure (ICP), cerebral perfusion pressure (CPP), and transcranial Doppler (TCD) velocities. We hypothesized that these parameters alone were not sufficient to assess the risk of cerebral ischemia.

Recurrences and rechallenges of suspected drugs in epidermal necrolysis patients.

Background: Epidermal necrolysis (EN) is a rare and severe condition, characterized by a diffuse skin and mucosal detachment and mainly induced by drugs. Literature is scarce regarding the rate of recurrences and culprit drug re-exposure.

Objectives: To assess the rate of EN recurrences as well as high notoriety drugs re-exposures in patients with EN.

Predicting Antidepressant Treatment Response From Cortical Structure on MRI: A Mega-Analysis From the ENIGMA-MDD Working Group.

Accurately predicting individual antidepressant treatment response could expedite the lengthy trial-and-error process of finding an effective treatment for major depressive disorder (MDD). We tested and compared machine learning-based methods that predict individual-level pharmacotherapeutic treatment response using cortical morphometry from multisite longitudinal cohorts. We conducted an international analysis of pooled data from six sites of the ENIGMA-MDD consortium (n = 262 MDD patients; age = 36.

Hypereosinophilia and Hypereosinophilic Syndromes: First Findings From a Nationwide Multicenter Cohort.

Background: Hypereosinophilic syndromes (HES) are a heterogenous group of eosinophilic disorders. To date, only retrospective studies of limited sample-size and/or follow-up duration are available.

Methods: The COHESion study is a national prospective multicenter multidisciplinary cohort recruiting both adults or children with the spectrum of eosinophilic disorders (including reactive HE/HES [HE/HES-R], idiopathic HES [HES-I], lymphocytic HES [HES-L], neoplastic HE/HES [HE/HES-N], HE of unknown significance [HE-US], as well as IgG4-related disease [IgG4RD] or ANCA-negative eosinophilic granulomatosis with polyangiitis [EGPA] overlaps).