Targeting PKCa alleviates iron overload in diabetes and hemochromatosis through the inhibition of ferroportin.

Ferroportin (Fpn) is the only iron exporter, playing a crucial role in systemic iron homeostasis. Fpn is negatively regulated by its ligand hepcidin, but other potential regulators in physiological and disease conditions remain poorly understood. Diabetes is a metabolic disorder that develops body iron loading with unknown mechanisms. By utilizing diabetic mouse models and human duodenal specimens, we demonstrated that intestinal Fpn expression was increased in diabetes in a hepcidin-independent manner. Protein kinase C (PKC) is hyperactivated in diabetes. We showed that PKC was required to sustain baseline Fpn expression and diabetes induced Fpn upregulation in the enterocytes and macrophages. Knockout of PKC abolished diabetes associated iron overload. Mechanistically, activation of PKC increased the exocytotic while decreased the endocytic trafficking of Fpn in the resting state. Hyperactive PKC also suppressed hepcidin-induced ubiquitination, internalization, and degradation of Fpn. We further observed that iron loading in the enterocytes and macrophages activated PKC, acting as a novel mechanism to enhance Fpn-dependent iron efflux. Finally, we demonstrated that the loss-of-function of PKC and pharmacological inhibition of PKC significantly alleviated hereditary hemochromatosis associated iron overload. Our study has highlighted, for the first time, that PKC is an important positive regulator of Fpn and a new target in the control of iron homeostasis.

Shaping an evanescent focus of light for high spatial resolution optogenetic activations in live cells.

Confining light illumination in the three dimensions of space is a challenge for various applications. Among these, optogenetic methods developed for live experiments in cell biology would benefit from such a localized illumination as it would improve the spatial resolution of diffusive photosensitive proteins leading to spatially constrained biological responses in specific subcellular organelles. Here, we describe a method to create and move a focused evanescent spot, at the interface between a glass substrate and an aqueous sample, across the field of view of a high numerical aperture microscope objective, using a digital micro-mirror device (DMD). We show that, after correcting the optical aberrations, light is confined within a spot of sub-micron lateral size and ∼100 nm axial depth above the coverslip, resulting in a volume of illumination drastically smaller than the one generated by a standard propagative focus. This evanescent focus is sufficient to induce a more intense and localized recruitment compared to a propagative focus on the optogenetic system CRY2-CIBN, improving the resolution of its pattern of activation.

ILAE neuroimaging task force highlight: Subcortical laminar heterotopia.

The ILAE Neuroimaging Task Force publishes educational case reports that highlight basic aspects of neuroimaging in epilepsy consistent with the ILAE's educational mission. Subcortical laminar heterotopia, also known as subcortical band heterotopia (SBH) or "double cortex," is an intriguing and rare congenital malformation of cortical development. SBH lesions are part of a continuum best designated as agyria-pachygyria-band-spectrum. The malformation is associated with epilepsy that is often refractory, as well as variable degrees of developmental delay. Moreover, in an increasing proportion of cases, a distinct molecular-genetic background can be found. Diagnosing SBH can be a major challenge for many reasons, including more subtle lesions, and "non-classic" or unusual MRI-appearances. By presenting an illustrative case, we address the challenges and needs of diagnosing and treating SBH patients in epilepsy, especially the value of high-resolution imaging and specialized MRI-protocols.

Anti-PF4 antibodies and their relationship with COVID infection.

Detecting anti-PF4 antibodies remains the golden diagnostic method for heparin-induced thrombocytopenia (HIT) diagnosis with high sensitivity and specificity. Various lab tests detect anti-PF4 antibodies, including immunoassays and functional assays. Even with positive detection of the anti-PF4 antibody, several factors are involved in the result. The concept of anti-PF4 disorders was recently brought to light during the COVID pandemic since the development of vaccine-induced thrombotic thrombocytopenia (VITT) with the adenovirus-vectored-DNA vaccine during the pandemic. Circumstances that detect anti-PF4 antibodies are classified as anti-PF4 disorders, including VITT, autoimmune HIT and spontaneous HIT. Some studies showed a higher percentage of anti-PF4 antibody detection among the population infected by COVID-19 without heparin exposure and some supported the theory that the anti-PF4 antibodies were related to the disease severity. In this review article, we provide a brief review of anti-PF4 disorders and summarize the current studies of anti-PF4 antibodies and COVID-19 infection.

Targeting PKC alleviates iron overload in diabetes and hemochromatosis.

Diabetes is one of the most prevalent chronic diseases worldwide. Iron overload increases the incidence of diabetes and aggravates diabetic complications that cause mortality. Reciprocally, diabetes potentially promotes body iron loading, but the mechanism remains not well understood. In this study, we demonstrated systemic iron excess and the upregulation of iron exporter ferroportin (Fpn) in the enterocytes and macrophages of multiple diabetic mouse models. Increased Fpn expression and iron efflux was also seen in the enterocytes of type 2 diabetic human patients. We further showed that protein kinase C (PKC), which is activated in hyperglycemia, was responsible for the sustained membrane expression of Fpn in physiological and in diabetic settings. For the first time, we identified that PKCs were novel binding proteins and positive regulators of Fpn. Mechanistically, hyperactive PKC promoted exocytotic membrane insertion while inhibited the endocytic trafficking of Fpn in the resting state. PKC also protected Fpn from internalization and degradation by its ligand hepcidin dependent on decreased ubiquitination and increased phosphorylation of Fpn. Importantly, the loss-of-function and pharmacological inhibition of PKC alleviated systemic iron overload in diabetes and hemochromatosis. Our study thus highlights PKC as a novel target in the control of systemic iron homeostasis.

Imaging through a square multimode fiber by scanning focused spots with the memory effect.

The existence of a shift-shift memory effect in square waveguides, whereby any translation of the input field induces translations in the output field in four symmetrical directions, has been previously observed by correlation measurements. Here we demonstrate that this memory effect is also observed in real space and can be put to use for imaging purposes. First, a focus is created at the output of a square-core multimode fiber, by wavefront shaping based on feedback from a guide-star. Then, because of the memory effect, four symmetrical spots can be scanned at the fiber output by shifting the wavefront at the fiber input. We demonstrate that this property can be exploited to perform fluorescence imaging through the multimode fiber, without requiring the measurement of a transmission matrix.

Force propagation between epithelial cells depends on active coupling and mechano-structural polarization.

Cell-generated forces play a major role in coordinating the large-scale behavior of cell assemblies, in particular during development, wound healing, and cancer. Mechanical signals propagate faster than biochemical signals, but can have similar effects, especially in epithelial tissues with strong cell-cell adhesion. However, a quantitative description of the transmission chain from force generation in a sender cell, force propagation across cell-cell boundaries, and the concomitant response of receiver cells is missing. For a quantitative analysis of this important situation, here we propose a minimal model system of two epithelial cells on an H-pattern ('cell doublet'). After optogenetically activating RhoA, a major regulator of cell contractility, in the sender cell, we measure the mechanical response of the receiver cell by traction force and monolayer stress microscopies. In general, we find that the receiver cells show an active response so that the cell doublet forms a coherent unit. However, force propagation and response of the receiver cell also strongly depend on the mechano-structural polarization in the cell assembly, which is controlled by cell-matrix adhesion to the adhesive micropattern. We find that the response of the receiver cell is stronger when the mechano-structural polarization axis is oriented perpendicular to the direction of force propagation, reminiscent of the Poisson effect in passive materials. We finally show that the same effects are at work in small tissues. Our work demonstrates that cellular organization and active mechanical response of a tissue are key to maintain signal strength and lead to the emergence of elasticity, which means that signals are not dissipated like in a viscous system, but can propagate over large distances.

Speckle-correlation imaging through a kaleidoscopic multimode fiber.

Speckle-correlation imaging techniques are widely used for noninvasive imaging through complex scattering media. While light propagation through multimode fibers and scattering media share many analogies, reconstructing images through multimode fibers from speckle correlations remains an unsolved challenge. Here, we exploit a kaleidoscopic memory effect emerging in square-core multimode fibers and demonstrate fluorescence imaging with no prior knowledge on the fiber. Experimentally, our approach simply requires to translate random speckle patterns at the input of a square-core fiber and to measure the resulting fluorescence intensity with a bucket detector. The image of the fluorescent object is then reconstructed from the autocorrelation of the measured signal by solving an inverse problem. This strategy does not require the knowledge of the fragile deterministic relation between input and output fields, which makes it promising for the development of flexible minimally invasive endoscopes.

Neurocysticercosis and epilepsy: Imaging and clinical characteristics.

The ILAE Neuroimaging Task Force aimed to publish educational case reports highlighting basic aspects related to neuroimaging in epilepsy consistent with the educational mission of the ILAE. Neurocysticercosis (NCC) is highly endemic in resource-limited countries and increasingly more often seen in non-endemic regions due to migration. Cysts with larva of the tapeworm Taenia solium lodge in the brain and cause several neurological conditions, of which seizures are the most common. There is great heterogeneity in the clinical presentation of neurocysticercosis because cysts vary in number, larval stage, and location among patients. We here present two illustrative cases with different clinical features to highlight the varying severity of symptoms secondary to this parasitic infestation. We also present several examples of imaging characteristics of the disease at various stages, which emphasize the central role of neuroimaging in the diagnosis of neurocysticercosis.

Low-Temperature Gas-Phase Kinetics of Ethanol-Methanol Heterodimer Formation.

The structures of gas-phase noncovalently bound clusters have long been studied in supersonic expansions. This method of study, while providing a wealth of information about the nature of noncovalent bonds, precludes observation of the formation of the cluster, as the clusters form just after the orifice of the pulsed valve. Here, we directly observe formation of ethanol-methanol dimers via microwave spectroscopy in a controlled cryogenic environment. Time profiles of the concentration of reagents in the cell yielded gas-phase reaction rate constants of kMe-g = (2.8 ± 1.4) × 10-13 cm3 molecule-1 s-1 and kMe-t = (1.6 ± 0.8) × 10-13 cm3 molecule-1 s-1 for the pseudo-second-order ethanol-methanol dimerization reaction at 8 K. The relaxation cross section between the gauche and trans conformers of ethanol was also measured using the same technique. In addition, thermodynamic relaxation between conformers of ethanol over time allowed for selection of conformer stoichiometry in the ethanol-methanol dimerization reaction, but no change in the ratio of dimer conformers was observed with changing ethanol monomer stoichiometry.

Multimodal mapping of regional brain vulnerability to focal cortical dysplasia.

Focal cortical dysplasia (FCD) type II is a highly epileptogenic developmental malformation and a common cause of surgically treated drug-resistant epilepsy. While clinical observations suggest frequent occurrence in the frontal lobe, mechanisms for such propensity remain unexplored. Here, we hypothesized that cortex-wide spatial associations of FCD distribution with cortical cytoarchitecture, gene expression and organizational axes may offer complementary insights into processes that predispose given cortical regions to harbour FCD. We mapped the cortex-wide MRI distribution of FCDs in 337 patients collected from 13 sites worldwide. We then determined its associations with (i) cytoarchitectural features using histological atlases by Von Economo and Koskinas and BigBrain; (ii) whole-brain gene expression and spatiotemporal dynamics from prenatal to adulthood stages using the Allen Human Brain Atlas and PsychENCODE BrainSpan; and (iii) macroscale developmental axes of cortical organization. FCD lesions were preferentially located in the prefrontal and fronto-limbic cortices typified by low neuron density, large soma and thick grey matter. Transcriptomic associations with FCD distribution uncovered a prenatal component related to neuroglial proliferation and differentiation, likely accounting for the dysplastic makeup, and a postnatal component related to synaptogenesis and circuit organization, possibly contributing to circuit-level hyperexcitability. FCD distribution showed a strong association with the anterior region of the antero-posterior axis derived from heritability analysis of interregional structural covariance of cortical thickness, but not with structural and functional hierarchical axes. Reliability of all results was confirmed through resampling techniques. Multimodal associations with cytoarchitecture, gene expression and axes of cortical organization indicate that prenatal neurogenesis and postnatal synaptogenesis may be key points of developmental vulnerability of the frontal lobe to FCD. Concordant with a causal role of atypical neuroglial proliferation and growth, our results indicate that FCD-vulnerable cortices display properties indicative of earlier termination of neurogenesis and initiation of cell growth. They also suggest a potential contribution of aberrant postnatal synaptogenesis and circuit development to FCD epileptogenicity.

Possible post-COVID epilepsy: A review of epilepsy monitoring unit admissions during the two years of COVID-19 pandemic.

Large scale healthcare data shows that new-onset epilepsy is noted in 0.3 % patients within 6 months of COVID-19 infection. We analyzed diagnostic epilepsy monitoring unit (EMU) evaluations to identify and report such cases. We thoroughly reviewed our EMU database and identified patients having "COVID" or "Corona" virus mention in their medical record from 03/15/2020 to 02/28/2022. Patients with epilepsy prior to COVID infection were excluded. Among 62 patients without prior epilepsy evaluated in the EMU for new-onset spells after confirmed COVID-19 infection, three patients were diagnosed with focal epilepsy. These three women without epilepsy risk factors had seizure onset at the time of, or within one to three months of, COVID-19 diagnosis. Their 3 T MRI imaging was non-lesional but revealed bilateral enlarged perivascular spaces. The video EEG monitoring was consistent with temporal or fronto-temporal lobe epilepsy in all three patients. Two of them developed drug-resistant epilepsy within six months of seizure onset. Our thorough analysis of diagnostic EMU evaluations during the two years of pandemic reveals three cases of post-COVID-19 epilepsy after non-symptomatic to mild disease. Although coincidental epilepsy onset cannot be ruled out, larger multicenter or national database investigations are needed to further analyze the possibility of post-COVID epilepsy.

Inter-individual variability in dorsal stream dynamics during word production.

The current standard model of language production involves a sensorimotor dorsal stream connecting areas in the temporo-parietal junction with those in the inferior frontal gyrus and lateral premotor cortex. These regions have been linked to various aspects of word production such as phonological processing or articulatory programming, primarily through neuropsychological and functional imaging group studies. Most if not all the theoretical descriptions of this model imply that the same network should be identifiable across individual speakers. We tested this hypothesis by quantifying the variability of activation observed across individuals within each dorsal stream anatomical region. This estimate was based on electrical activity recorded directly from the cerebral cortex with millisecond accuracy in awake epileptic patients clinically implanted with intracerebral depth electrodes for pre-surgical diagnosis. Each region's activity was quantified using two different metrics-intra-cerebral evoked related potentials and high gamma activity-at the level of the group, the individual and the recording contact. The two metrics show simultaneous activation of parietal and frontal regions during a picture naming task, in line with models that posit interactive processing during word retrieval. They also reveal different levels of between-patient variability across brain regions, except in core auditory and motor regions. The independence and non-uniformity of cortical activity estimated through the two metrics push the current model towards sub-second and sub-region explorations focused on individualized language speech production. Several hypotheses are considered for this within-region heterogeneity.

Automated Fabrication of Streptavidin-Based Self-assembled Materials for High-Content Analysis of Cellular Response to Growth Factors.

The automation of liquid-handling routines offers great potential for fast, reproducible, and labor-reduced biomaterial fabrication but also requires the development of special protocols. Competitive systems demand for a high degree in miniaturization and parallelization while maintaining flexibility regarding the experimental design. Today, there are only a few possibilities for automated fabrication of biomaterials inside multiwell plates. We have previously demonstrated that streptavidin-based biomimetic platforms can be employed to study cellular behaviors on biomimetic surfaces. So far, these self-assembled materials were made by stepwise assembly of the components using manual pipetting. In this work, we introduce for the first time a fully automated and adaptable workflow to functionalize glass-bottom multiwell plates with customized biomimetic platforms deposited in single wells using a liquid-handling robot. We then characterize the cell response using automated image acquisition and subsequent analysis. Furthermore, the molecular surface density of the biomimetic platforms was characterized in situ using fluorescence-based image correlation spectroscopy. These measurements were in agreement with standard ex situ spectroscopic ellipsometry measurements. Due to automation, we could do a proof of concept to study the effect of heparan sulfate on the bioactivity of bone morphogenetic proteins on myoblast cells, using four different bone morphogenetic proteins (BMPs) (2, 4, 6, and 7) in parallel, at five increasing concentrations. Using such an automated self-assembly of biomimetic materials, it may be envisioned to further investigate the role of a large variety of extracellular matrix (ECM) components and growth factors on cell signaling.

Combining Fluorescence Fluctuations and Photobleaching to Quantify Surface Density.

We have established a self-calibrated method, called pbFFS for photobleaching fluctuation fluorescence spectroscopy, which aims to characterize molecules or particles labeled with an unknown distribution of fluorophores. Using photobleaching as a control parameter, pbFFS provides information on the distribution of fluorescent labels and a reliable estimation of the absolute density or concentration of these molecules. We present a complete theoretical derivation of the pbFFS approach and experimentally apply it to measure the surface density of a monolayer of fluorescently tagged streptavidin molecules, which can be used as a base platform for biomimetic systems. The surface density measured by pbFFS is consistent with the results of spectroscopic ellipsometry, a standard surface technique. However, pbFFS has two main advantages: it enables in situ characterization (no dedicated substrates are required) and can be applied to low masses of adsorbed molecules, which we demonstrate here by quantifying the density of biotin-Atto molecules that bind to the streptavidin layer. In addition to molecules immobilized on a surface, we also applied pbFFS to molecules diffusing in solution, to confirm the distribution of fluorescent labels found on a surface. Hence, pbFFS provides a set of tools for investigating the molecules labeled with a variable number of fluorophores, with the aim of quantifying either the number of molecules or the distribution of fluorescent labels, the latter case being especially relevant for oligomerization studies.

Fractionated Proton Radiation Therapy and Hearing Preservation for Vestibular Schwannoma: Preliminary Analysis of a Prospective Phase 2 Clinical Trial.

BACKGROUND: Local management for vestibular schwannoma (VS) is associated with excellent local control with focus on preserving long-term serviceable hearing. Fractionated proton radiation therapy (FPRT) may be associated with greater hearing preservation because of unique dosimetric properties of proton radiotherapy. OBJECTIVE: To investigate hearing preservation rates of FPRT in adults with VS and secondarily assess local control and treatment-related toxicity. METHODS: A prospective, single-arm, phase 2 clinical trial was conducted of patients with VS from 2010 to 2019. All patients had serviceable hearing at baseline and received FPRT to a total dose of 50.4 to 54 Gy relative biological effectiveness (RBE) over 28 to 30 fractions. Serviceable hearing preservation was defined as a Gardner-Robertson score of 1 to 2, measured by a pure tone average (PTA) of ≤50 dB and a word recognition score (WRS) of ≥50%. RESULTS: Twenty patients had a median follow-up of 4.0 years (range 1.0-5.0 years). Local control at 4 years was 100%. Serviceable hearing preservation at 1 year was 53% (95% CI 29%-76%), and primary end point was not yet reached. Median PTA and median WRS both worsened 1 year after FPRT (P < .0001). WRS plateaued after 6 months, whereas PTA continued to worsen up to 1 year after FPRT. Median cochlea D90 was lower in patients with serviceable hearing at 1 year (40.6 Gy [RBE] vs 46.9 Gy [RBE]), trending toward Wilcoxon rank-sum test statistical significance (P = .0863). Treatment was well-tolerated, with one grade 1 cranial nerve V dysfunction and no grade 2+ cranial nerve dysfunction. CONCLUSION: FPRT for VS did not meet the goal of serviceable hearing preservation. Higher cochlea doses trended to worsening hearing preservation, suggesting that dose to cochlea correlates with hearing preservation independent of treatment modality.

Optical nanotopography of fluorescent surfaces by axial position modulation.

We present an optical method that combines confocal microscopy with position modulation to perform axial tracking and topographic imaging of fluorescent surfaces. Using a remote focusing system, the confocal observation volume is oscillated in the axial direction. The resulting modulation of the detected signal is used as a feedback to precisely control the distance to an object of interest. The accuracy of this method is theoretically analyzed and the axial-locking accuracy is experimentally evaluated. Topographic imaging is demonstrated on fluorescently coated beads and fixed cells. This microscope allows for nanometric topography or tracking of dynamic fluorescent surfaces.

Associations of patient-reported care satisfaction with symptom burden and healthcare use in hospitalized patients with cancer.

BACKGROUND: Hospitalized patients with cancer often experience a high symptom burden, which may impact care satisfaction and healthcare utilization. METHODS: We prospectively enrolled patients with cancer and unplanned hospitalizations from September 2014 to April 2017. Upon admission, we assessed patients' care satisfaction (FAMCARE items: satisfaction with care coordination and speed with which symptoms are treated) and physical (Edmonton Symptom Assessment System [ESAS]) and psychological (Patient Health Questionnaire-4 [PHQ-4]) symptoms. We used regression models to identify factors associated with care satisfaction and associations of satisfaction with symptom burden and hospital length of stay (LOS). RESULTS: Among 1,576 participants, most reported being "satisfied"/ "very satisfied" with care coordination (90%) and speed with which symptoms are treated (89%). Older age (coordination: B < 0.01, P = 0.02, speed: B = 0.01, P < 0.01) and admission to a dedicated oncology service (B = 0.20, P < 0.01 for each) were associated with higher satisfaction. Higher satisfaction with care coordination was associated with lower ESAS-physical (B = - 1.28, P < 0.01), ESAS-total (B = - 2.73, P < 0.01), PHQ4-depression (B = - 0.14, P = 0.02), and PHQ4-anxiety (B = - 0.16, P < 0.01) symptoms. Higher satisfaction with speed with which symptoms are treated was associated with lower ESAS-physical (B = - 1.32, P < 0.01), ESAS-total (B = - 2.46, P < 0.01), PHQ4-depression (B = - 0.14, P = 0.01), and PHQ4-anxiety (B = - 0.17, P < 0.01) symptoms. Satisfaction with care coordination (B = - 0.48, P = 0.04) and speed with which symptoms are treated (B = - 0.44, P = 0.04) correlated with shorter LOS. CONCLUSIONS: Hospitalized patients with cancer report high care satisfaction, which correlates with older age and admission to a dedicated oncology service. Significant associations among higher care satisfaction, lower symptom burden, and shorter hospital LOS highlight the importance of improving symptom management and care coordination in this population.

Management of Frail and Older Homebound Patients With Heart Failure: A Contemporary Virtual Ambulatory Model.

BACKGROUND: Heart failure (HF) affects many patients who are older and frail, presenting multiple physical barriers to accessing specialty care in a traditional ambulatory clinic model. Here, we present an assisted virtual care model in which a home visiting nurse facilitated video visits with a HF cardiologist to follow homebound, frail, and older patients with HF. METHODS: This is a pragmatic, quasi-experimental, pre-post, single-centre study. It included homebound, frail, and older patients with HF from 2015 to 2019 who were followed for 1 year; in-person clinic visits were completely replaced by nurse-facilitated virtual video visits. Outcomes evaluated included annualized hospitalization rate, number of hospitalization days, and number of emergency department visits. RESULTS: A total of 49 patients were included, with a median age of 86 (83-93) years, and were followed for 1 year after enrollment. Among patients enrolled, HF with preserved ejection fraction was the most common subtype (57%). Compared to the year prior to enrollment, patients had a lower mortality-adjusted all-cause annualized hospitalization rate in the year following enrollment (2.57 vs 1.78, P < 0.0001). Compared to the year prior, the number of mortality-adjusted all-cause hospitalization days was significantly lower in the year following enrollment (27.2 vs 21.4, P < 0.0001). There was a reduction in the number of all-cause annualized emergency department visits (3.10 vs 2.27, P = 0.003). CONCLUSIONS: Nurse-assisted virtual visits may be a preferable strategy for homebound, frail, and older patients with HF to receive longitudinal care. This approach may represent a plausible strategy to care for other patients with significant barriers to accessing specialized cardiac care.

CONTEXTE: L'insuffisance cardiaque (IC) touche de nombreux patients âgés et fragiles, et dresse maints obstacles physiques à l'accès aux soins spécialisés au sein d'un modèle classique de soins cliniques ambulatoires. Dans le présent article, nous exposons un modèle de soins virtuels assistés où une infirmière visiteuse assure par vidéoconsultation, avec un cardiologue, le suivi de patients âgés et fragiles atteints d'IC confinés à la maison. MÉTHODOLOGIE: Une étude monocentrique et pragmatique, quasi expérimentale de type « avant-après ¼, a été menée de 2015 à 2019 auprès de patients âgés et fragiles atteints d'IC confinés à la maison. Les patients ont été suivis durant un an; les consultations en personne ont été entièrement remplacées par des vidéoconsultations effectuées par une infirmière. Les paramètres évalués comprenaient le taux annualisé d'hospitalisation, le nombre de jours d'hospitalisation et le nombre de consultations aux urgences. RÉSULTATS: Au total, 49 patients dont l'âge médian était de 86 ans (83-93 ans) ont été suivis durant un an à compter de leur admission à l'étude. L'IC à fraction d'éjection préservée était le sous-type d'IC le plus fréquent (57 %) chez les patients participant à l'étude. Par comparaison à l'année précédente, le taux annualisé d'hospitalisation toutes causes confondues ajusté en fonction de la mortalité a été plus faible chez les patients au cours de l'année où ils ont été suivis dans le cadre de l'étude (2,57 vs 1,78, P < 0,0001). Toujours par comparaison à l'année précédente, le nombre de jours d'hospitalisation toutes causes confondues ajusté en fonction de la mortalité a été significativement inférieur chez les patients au cours de l'année où ils ont été suivis dans le cadre de l'étude (27,2 vs 21,4, P < 0,0001). Le nombre annualisé de consultations aux urgences toutes causes confondues a quant à lui diminué (3,10 vs 2,27, P = 0,003). CONCLUSIONS: Les consultations virtuelles assistées par une infirmière peuvent constituer une stratégie à privilégier dans la prestation de soins longitudinaux à des patients âgés et fragiles atteints d'IC qui sont confinés à la maison. Cette approche pourrait représenter une stratégie plausible pour prodiguer des soins à d'autres patients qui sont confrontés à d'importants obstacles limitant leur accès à des soins spécialisés en cardiologie.

Atlas of lesion locations and postsurgical seizure freedom in focal cortical dysplasia: A MELD study.

OBJECTIVE: Drug-resistant focal epilepsy is often caused by focal cortical dysplasias (FCDs). The distribution of these lesions across the cerebral cortex and the impact of lesion location on clinical presentation and surgical outcome are largely unknown. We created a neuroimaging cohort of patients with individually mapped FCDs to determine factors associated with lesion location and predictors of postsurgical outcome. METHODS: The MELD (Multi-centre Epilepsy Lesion Detection) project collated a retrospective cohort of 580 patients with epilepsy attributed to FCD from 20 epilepsy centers worldwide. Magnetic resonance imaging-based maps of individual FCDs with accompanying demographic, clinical, and surgical information were collected. We mapped the distribution of FCDs, examined for associations between clinical factors and lesion location, and developed a predictive model of postsurgical seizure freedom. RESULTS: FCDs were nonuniformly distributed, concentrating in the superior frontal sulcus, frontal pole, and temporal pole. Epilepsy onset was typically before the age of 10 years. Earlier epilepsy onset was associated with lesions in primary sensory areas, whereas later epilepsy onset was associated with lesions in association cortices. Lesions in temporal and occipital lobes tended to be larger than frontal lobe lesions. Seizure freedom rates varied with FCD location, from around 30% in visual, motor, and premotor areas to 75% in superior temporal and frontal gyri. The predictive model of postsurgical seizure freedom had a positive predictive value of 70% and negative predictive value of 61%. SIGNIFICANCE: FCD location is an important determinant of its size, the age at epilepsy onset, and the likelihood of seizure freedom postsurgery. Our atlas of lesion locations can be used to guide the radiological search for subtle lesions in individual patients. Our atlas of regional seizure freedom rates and associated predictive model can be used to estimate individual likelihoods of postsurgical seizure freedom. Data-driven atlases and predictive models are essential for evidence-based, precision medicine and risk counseling in epilepsy.