Intractable conflicts over end-of-life decisions: A descriptive and ethical analysis of French case-law.

Context: In European and Anglo-Saxon countries, life-sustaining treatment (LST) limitation decisions precede more than 80% of ICU deaths. However, there is now increasing evidence of disagreement and conflict between clinical teams and family members over LST limitation decisions. In some cases, these conflicts are brought to the courts.

Repeated exposure to low doses of light induces retinal damage in vivo in a wavelength-dependent manner.

The exposure of the general population to artificial light at night has dramatically increased in recent decades. Current standards for domestic lighting are based on acute exposure to light and consider blue wavelengths to be responsible for phototoxicity. However, meta-analyses pointed out the role of lifelong light exposure in the onset of age-related macular degeneration, suggesting a cumulative effect of light exposure.

One- or Two-Step Total Thyroidectomy for Cancer Indications: A 20-Year Retrospective Study from a Referral Center.

Background: The ATA guidelines suggest lobectomy as an option for select patients with thyroid cancer (TC), but some may need completion thyroidectomy because of unfavorable characteristics on the final pathology. This study aimed to compare postoperative morbidity of patients with TC who underwent total thyroidectomy in two steps (TT2) or one step (TT1).

Methods: This was a retrospective comparative study in a high-volume endocrine surgery center.

Expression of Yes-associated protein in endothelial cells of human corneas before and after storage in organ culture.

The cornea, the anterior meniscus-shaped transparent and refractive structure of the eyeball, is the first mechanical barrier of the eye. Its functionality heavily relies on the health of its endothelium, its most posterior layer. The treatment of corneal endothelial cells (CECs) deficiency is allogeneic corneal graft using stored donor corneas.

Predicting corneal decompensation in Fuchs endothelial corneal dystrophy with Scheimpflug tomography and clinical parameters.

Purpose: This study aims to evaluate the efficacy of various tomographic indices, both established and novel, in predicting endothelial decompensation leading to either spontaneous corneal transplantation or transplantation following cataract surgery in patients with Fuchs endothelial corneal dystrophy (FECD).

Methods: In this cross-sectional, retrospective study, we reviewed the files of 93 eyes from 54 FECD patients undergoing regular follow-up. We recorded clinical metrics such as morning visual disturbance (MVD) and corrected distance visual acuity.

Impact on clinical guideline adherence of Orient-COVID, a clinical decision support system based on dynamic decision trees for COVID19 management: A randomized simulation trial with medical trainees.

Background: The adherence of clinicians to clinical practice guidelines is known to be low, including for the management of COVID-19, due to their difficult use at the point of care and their complexity. Clinical decision support systems have been proposed to implement guidelines and improve adherence. One approach is to permit the navigation inside the recommendations, presented as a decision tree, but the size of the tree often limits this approach and may cause erroneous navigation, especially when it does not fit in a single screen.

Hepatocellular carcinoma hosts cholinergic neural cells and tumoral hepatocytes harboring targetable muscarinic receptors.

Background & Aims: Owing to unexplained interpatient variation and treatment failure in hepatocellular carcinoma (HCC), novel therapeutic approaches remain an urgent clinical need. Hepatic neurons, belonging to the autonomic nervous system (ANS), mediate liver/whole body crosstalk. Pathological innervation of the ANS has been identified in cancer, nurturing tumor stroma and conferring stronger carcinogenic properties.

Prediction of the need of enteral nutrition during radiation therapy for head and neck cancers.

Introduction: Patients with a head and neck (HN) cancer undergoing radiotherapy risk critical weight loss and oral intake reduction leading to enteral nutrition. We developed a predictive model for the need for enteral nutrition during radiotherapy in this setting. Its performances were reported on a real-world multicentric cohort.

Similar deficiencies, different outcomes: succinate dehydrogenase loss in adrenal medulla vs. fibroblast cell culture models of paraganglioma.

Heterozygosity for loss-of-function alleles of the genes encoding the four subunits of succinate dehydrogenase (SDHA, SDHB, SDHC, SDHD), as well as the SDHAF2 assembly factor predispose affected individuals to pheochromocytoma and paraganglioma (PPGL), two rare neuroendocrine tumors that arise from neural crest-derived paraganglia. Tumorigenesis results from loss of the remaining functional SDHx gene copy, leading to a cell with no functional SDH and a defective tricarboxylic acid (TCA) cycle. It is believed that the subsequent accumulation of succinate competitively inhibits multiple dioxygenase enzymes that normally suppress hypoxic signaling and demethylate histones and DNA, ultimately leading to increased expression of genes involved in angiogenesis and cell proliferation.

Half-Life Extension of the IgG-Degrading Enzyme (IdeS) Using Fc-Fusion Technology.

Imlifidase (IdeS) is a bacterial protease that hydrolyzes human IgG in their hinge region, decreasing their half-life and abrogating their Fc-mediated properties. It is now successfully used in therapy to prevent graft rejection during kidney transplants and is being clinically evaluated in several IgG-mediated autoimmune diseases. IdeS short half-life however limits its clinical use, particularly in the case of chronic diseases that would request repeated administrations.

AI-based classification of anticancer drugs reveals nucleolar condensation as a predictor of immunogenicity.

Background: Immunogenic cell death (ICD) inducers are often identified in phenotypic screening campaigns by the release or surface exposure of various danger-associated molecular patterns (DAMPs) from malignant cells. This study aimed to streamline the identification of ICD inducers by leveraging cellular morphological correlates of ICD, specifically the condensation of nucleoli (CON).

Methods: We applied artificial intelligence (AI)-based imaging analyses to Cell Paint-stained cells exposed to drug libraries, identifying CON as a marker for ICD.

Pushing the boundaries of radiotherapy-immunotherapy combinations: highlights from the 7 immunorad conference.

Over the last decade, the annual Immunorad Conference, held under the joint auspicies of Gustave Roussy (Villejuif, France) and the Weill Cornell Medical College (New-York, USA) has aimed at exploring the latest advancements in the fields of tumor immunology and radiotherapy-immunotherapy combinations for the treatment of cancer. Gathering medical oncologists, radiation oncologists, physicians and researchers with esteemed expertise in these fields, the Immunorad Conference bridges the gap between preclinical outcomes and clinical opportunities. Thus, it paves a promising way toward optimizing radiotherapy-immunotherapy combinations and, from a broader perspective, improving therapeutic strategies for patients with cancer.

Digital twins for chronic lung diseases.

Digital twins have recently emerged in healthcare. They combine advances in cyber-physical systems, modelling and computation techniques, and enable a bidirectional flow of information between the physical and virtual entities. In respiratory medicine, progress in connected devices and artificial intelligence make it technically possible to obtain digital twins that allow real-time visualisation of a patient's respiratory health.

Active learning for extracting rare adverse events from electronic health records: A study in pediatric cardiology.

Objective: Automate the extraction of adverse events from the text of electronic medical records of patients hospitalized for cardiac catheterization.

Methods: We focused on events related to cardiac catheterization as defined by the NCDR-IMPACT registry. These events were extracted from the Necker Children's Hospital data warehouse.

PNPLA3 in Alcohol-Related Liver Disease.

The discovery of PNPLA3 as a genetic risk factor for liver disease has transformed our understanding of the pathogenesis of alcohol-related liver disease (ALD). The recent reclassification of fatty liver disease as steatotic liver disease (SLD), introducing metabolic dysfunction and alcohol-related liver disease (MetALD), has highlighted how genetic and environmental factors synergistically drive liver damage. The PNPLA3 rs738409 variant stands as a paradigmatic example of gene-environment interaction, where its effect on liver disease is dramatically amplified by alcohol consumption, obesity and type 2 diabetes.

An efficient joint model for high dimensional longitudinal and survival data via generic association features.

This paper introduces a prognostic method called FLASH that addresses the problem of joint modeling of longitudinal data and censored durations when a large number of both longitudinal and time-independent features are available. In the literature, standard joint models are either of the shared random effect or joint latent class type. Combining ideas from both worlds and using appropriate regularization techniques, we define a new model with the ability to automatically identify significant prognostic longitudinal features in a high-dimensional context, which is of increasing importance in many areas such as personalized medicine or churn prediction.

The Bronchodilator and Anti-Inflammatory Effect of Long-Acting Muscarinic Antagonists in Asthma: An EAACI Position Paper.

As cholinergic innervation is a major contributor to increased vagal tone and mucus secretion, inhaled long-acting muscarinic antagonists (LAMA) are a pillar for the treatment of chronic obstructive pulmonary disease and asthma. By blocking the muscarinic receptors expressed in the lung, LAMA improve lung function and reduce exacerbations in asthma patients who remained poorly controlled despite treatment with inhaled corticosteroids and long-acting β2 agonists. Asthma guidelines recommend LAMA as a third controller to be added on before the initiation of biologicals.

Prognostic value of circulating tumor DNA at diagnosis and its early decrease after one cycle of neoadjuvant chemotherapy for patients with advanced epithelial ovarian cancer. An ancillary analysis of the CHIVA phase II GINECO trial.

Objective: To evaluate the prognostic impact of circulating tumor DNA (ctDNA) detection at diagnosis (T0) and its early decrease after one cycle (T1) of neoadjuvant chemotherapy (NACT) in patients with advanced epithelial ovarian cancer (EOC) included in the CHIVA trial (NCT01583322).

Methods: Blood samples were collected at T0 and before each administration of NACT. Circulating tumor DNA detection was performed by next-generation sequencing.

Malnutrition and radiation therapy in head and neck cancers, a systematic review on reported definitions and associated factors.

Radiation therapy is a major treatment in head and neck cancers that can induce mucositis, pain, and dysgeusia that could impair oral intake and lead to weight loss and malnutrition. Intensity modulation has diminished toxicity of radiation therapy. We performed a review to assess the rate of malnutrition and how malnutrition was defined across cohorts of patients undergoing modern curative radiation therapy.

FVIII peptides presented on HLA-DP and identification of an A3 domain peptide binding with high affinity to the commonly expressed HLA-DP4.

The development of neutralizing antibodies (inhibitors) against coagulation factor VIII (FVIII) poses a major challenge in hemophilia A (HA) treatment. The formation of FVIII inhibitors is a CD4+ T-cell dependent mechanism which includes antigen presenting cells (APCs), B- and T-helper lymphocytes. APCs present FVIII derived peptides on major histocompatibility complex class II (MHC-II) to CD4+ Tcells.

Binding of therapeutic Fc-fused factor VIII to the neonatal Fc receptor at neutral pH associates with poor half-life extension.

Fusion of therapeutic proteins to the Fc fragment of human IgG1 promotes their FcRn-mediated recycling and subsequent extension in circulating half-life. However, different Fc-fused proteins, as well as antibodies with different variable domains but identical Fc, may differ in terms of extension in half-life. Here we compared the binding behaviour to FcRn of Fc-fused FVIII, Fc-fused FIX and two human monoclonal HIV-1 broadly-neutralizing IgG1, m66.

Acquired thrombotic thrombocytopenic purpura of unidentified pathophysiology in patients with severe disease: completing the landscape of thrombotic thrombocytopenic purpura.

Not available.

Lysosomal damage due to cholesterol accumulation triggers immunogenic cell death.

Cholesterol serves as a vital lipid that regulates numerous physiological processes. Nonetheless, its role in regulating cell death processes remains incompletely understood. In this study, we investigated the role of cholesterol trafficking in immunogenic cell death.