Soft tissue vascular tumor-like lesions in adults: imaging and pathological analysis pitfalls per ISSVA classification.

OBJECTIVES: To compare the magnetic resonance imaging (MRI) and Doppler ultrasound (DUS) findings with the pathological findings of soft tissue vascular tumors (STVTs) according to the 2018 ISSVA (International Society for the Study of Vascular Anomalies) classification to differentiate vascular tumors from vascular malformations. METHODS: This retrospective study included patients with STVTs who underwent contrast-enhanced MRI and pathological analysis at our hospital between 2010 and 2020. The presumptive diagnosis based on the on-site imaging and histological analysis was compared with imaging and histological analysis conducted off-site utilizing the ISSVA criteria. RESULTS: This study included 31 patients with 31 vascular tumors located in the head and neck (n = 3), trunk (n = 2), and extremities (n = 26). The off-site pathological analysis confirmed benign vascular tumors in 54.8% of cases (non-involuting congenital hemangioma: 35.5%; epithelioid hemangioma: 13%; pyogenic granuloma: 3%; and spindle cell hemangioma: 3%). Based on the off-site histological analysis, 25.8% were reclassified as having a vascular malformation whereas three had other benign lesions. Only phleboliths were associated with a vascular malformation (p = 0.03). The concordance between off-site MRI and pathological findings was fair (k = 0.3902 (0.0531-0.7274)), whereas that between on-site and off-site pathological analyses was poor (k = -0.0949 (-0.4661 to 0.2763)). CONCLUSION: Benign vascular tumors have non-specific imaging features on imaging with some overlap with atypical vascular malformations. Therefore, histological analysis is recommended. Imaging and pathological analyses should be performed in accordance with the ISSVA classification to minimize inter-observer discrepancies. CRITICAL RELEVANCE STATEMENT: Imaging features of benign vascular tumors on MRI are non-specific, leading to discrepancies with pathological findings and potential overlap with atypical vascular malformations. Imaging and histological analyses should be performed in accordance with ISSVA guidelines to improve patient management. KEY POINTS: The imaging features of benign vascular tumors are non-specific. Histological analysis is recommended for soft tissue vascular tumors in adults. Analyses of soft tissue vascular tumors should be performed in accordance with ISSVA guidelines.

Development of cortical folds in the human brain: An attempt to review biological hypotheses, early neuroimaging investigations and functional correlates.

The folding of the human brain mostly takes place in utero, making it challenging to study. After a few pioneer studies looking into it in post-mortem foetal specimen, modern approaches based on neuroimaging have allowed the community to investigate the folding process in vivo, its normal progression, its early disturbances, and its relationship to later functional outcomes. In this review article, we aimed to first give an overview of the current hypotheses on the mechanisms governing cortical folding. After describing the methodological difficulties raised by its study in fetuses, neonates and infants with magnetic resonance imaging (MRI), we reported our current understanding of sulcal pattern emergence in the developing brain. We then highlighted the functional relevance of early sulcal development, through recent insights about hemispheric asymmetries and early factors influencing this dynamic such as prematurity. Finally, we outlined how longitudinal studies have started to relate early folding markers and the child's sensorimotor and cognitive outcome. Through this review, we hope to raise awareness on the potential of studying early sulcal patterns both from a fundamental and clinical perspective, as a window into early neurodevelopment and plasticity in relation to growth in utero and postnatal environment of the child.

Depletion of CLL cells by venetoclax treatment reverses oxidative stress and impaired glycolysis in CD4 T cells.

Acquired T-cell dysfunction is characteristic of chronic lymphocytic leukemia (CLL) and is associated with reduced efficacy of T cell-based therapies. A recently described feature of dysfunctional CLL-derived CD8 T cells is reduced metabolic plasticity. To what extend CD4 T cells are affected and whether CD4 T-cell metabolism and function can be restored upon clinical depletion of CLL cells are currently unknown. We address these unresolved issues by comprehensive phenotypic, metabolic, transcriptomic, and functional analysis of CD4 T cells of untreated patients with CLL and by analysis of the effects of venetoclax plus obinutuzumab on the CD4 population. Resting CD4 T cells derived from patients with CLL expressed lower levels of GLUT-1 and displayed deteriorated oxidative phosphorylation (OXPHOS) and overall reduced mitochondrial fitness. Upon T-cell stimulation, CLL T cells were unable to initiate glycolysis. Transcriptome analysis revealed that depletion of CLL cells in vitro resulted in upregulation of OXPHOS and glycolysis pathways and restored T-cell function in vitro. Analysis of CD4 T cells from patients with CLL before and after venetoclax plus obinutuzumab treatment, which led to effective clearance of CLL in blood and bone marrow, revealed recovery of T-cell activation and restoration of the switch to glycolysis, as well as improved T-cell proliferation. Collectively, these data demonstrate that CLL cells impose metabolic restrictions on CD4 T cells, which leads to reduced CD4 T-cell functionality. This trial was registered in the Netherlands Trial Registry as #NTR6043.

Predictors of mortality, ICU hospitalization, and extrapulmonary complications in COVID-19 patients.

OBJECTIVE: A major coronavirus disease 2019 (COVID-19) outbreak occurred in Northeastern France in spring 2020. This single-center retrospective observational cohort study aimed to compare patients with severe COVID-19 and those with non-severe COVID-19 (survivors vs. non-survivors, ICU patients vs. non-ICU patients) and to describe extrapulmonary complications. PATIENTS AND METHODS: We included all patients with a confirmed diagnosis of COVID-19 admitted to Colmar Hospital in March 2020. RESULTS: We examined 600 patients (median age 71.09 years; median body mass index: 26.9 kg/m2); 57.7% were males, 86.3% had at least one comorbidity, 153 (25.5%) required ICU hospitalization, and 115 (19.1%) died. Baseline independent factors associated with death were older age (>75 vs. ≤75 years), male sex, oxygen supply, chronic neurological, renal, and pulmonary diseases, diabetes, cancer, low platelet and hemoglobin counts, and high levels of C-reactive protein (CRP) and serum creatinine. Factors associated with ICU hospitalization were age <75 years, oxygen supply, chronic pulmonary disease, absence of dementia, and high levels of CRP, hemoglobin, and serum creatinine. Among the 600 patients, 80 (13.3%) had an acute renal injury, 33 (5.5%) had a cardiovascular event, 27 (4.5%) had an acute liver injury, 24 (4%) had venous thromboembolism, eight (1.3%) had a neurological event, five (0.8%) had rhabdomyolysis, and one had acute pancreatitis. Most extrapulmonary complications occurred in ICU patients. CONCLUSION: This study highlighted the main risk factors for ICU hospitalization and death caused by severe COVID-19 and the frequency of numerous extrapulmonary complications in France.

Correlated charge noise and relaxation errors in superconducting qubits.

The central challenge in building a quantum computer is error correction. Unlike classical bits, which are susceptible to only one type of error, quantum bits (qubits) are susceptible to two types of error, corresponding to flips of the qubit state about the X and Z directions. Although the Heisenberg uncertainty principle precludes simultaneous monitoring of X- and Z-flips on a single qubit, it is possible to encode quantum information in large arrays of entangled qubits that enable accurate monitoring of all errors in the system, provided that the error rate is low1. Another crucial requirement is that errors cannot be correlated. Here we characterize a superconducting multiqubit circuit and find that charge noise in the chip is highly correlated on a length scale over 600 micrometres; moreover, discrete charge jumps are accompanied by a strong transient reduction of qubit energy relaxation time across the millimetre-scale chip. The resulting correlated errors are explained in terms of the charging event and phonon-mediated quasiparticle generation associated with absorption of γ-rays and cosmic-ray muons in the qubit substrate. Robust quantum error correction will require the development of mitigation strategies to protect multiqubit arrays from correlated errors due to particle impacts.

[11C]PBR28 MR-PET imaging reveals lower regional brain expression of translocator protein (TSPO) in young adult males with autism spectrum disorder.

Mechanisms of neuroimmune and mitochondrial dysfunction have been repeatedly implicated in autism spectrum disorder (ASD). To examine these mechanisms in ASD individuals, we measured the in vivo expression of the 18 kDa translocator protein (TSPO), an activated glial marker expressed on mitochondrial membranes. Participants underwent scanning on a simultaneous magnetic resonance-positron emission tomography (MR-PET) scanner with the second-generation TSPO radiotracer [11C]PBR28. By comparing TSPO in 15 young adult males with ASD with 18 age- and sex-matched controls, we showed that individuals with ASD exhibited lower regional TSPO expression in several brain regions, including the bilateral insular cortex, bilateral precuneus/posterior cingulate cortex, and bilateral temporal, angular, and supramarginal gyri, which have previously been implicated in autism in functional MR imaging studies. No brain region exhibited higher regional TSPO expression in the ASD group compared with the control group. A subset of participants underwent a second MR-PET scan after a median interscan interval of 3.6 months, and we determined that TSPO expression over this period of time was stable and replicable. Furthermore, voxelwise analysis confirmed lower regional TSPO expression in ASD at this later time point. Lower TSPO expression in ASD could reflect abnormalities in neuroimmune processes or mitochondrial dysfunction.

Nonadiabatic effects in the double ionization of atoms driven by a circularly polarized laser pulse.

We study the double ionization of atoms subjected to circularly polarized (CP) laser pulses. We analyze two fundamental ionization processes: the sequential (SDI) and nonsequential (NSDI) double ionization in the light of the rotating frame (RF) which naturally embeds nonadiabatic effects in CP pulses. We use and compare two adiabatic approximations: The adiabatic approximation in the laboratory frame (LF) and the adiabatic approximation in the RF. The adiabatic approximation in the RF encapsulates the energy variations of the electrons on subcycle timescales happening in the LF and this, by fully taking into account the ion-electron interaction. This allows us to identify two nonadiabatic effects including the lowering of the threshold intensity at which over-the-barrier ionization happens and the lowering of the ionization time of the electrons. As a consequence, these nonadiabatic effects facilitate over-the-barrier ionization and recollision-induced ionizations. We analyze the outcomes of these nonadiabatic effects on the recollision mechanism. We show that the laser envelope plays an instrumental role in a recollision channel in CP pulses at the heart of NSDI.

Polymorphisms of stress pathway genes and emergence of suicidal ideation at antidepressant treatment onset.

The prescription of antidepressant drugs is one of the most frequently used strategies to prevent suicide and suicidal behavior. However, some patients develop suicidal ideation at antidepressant treatment onset, a phenomenon known as treatment-emergent suicidal ideation (TESI). Few studies have explored TESI pharmacogenomics. As the Hypothalamic-Pituitary-Adrenal (HPA) axis might be implicated in suicidal behavior, we assessed the relationship between TESI and single nucleotide polymorphisms (SNPs) in the HPA axis-implicated NR3C1 (n = 7 SNPs), FKBP5 (n = 5 SNPs), AVPR1B (n = 1 SNPs), CRHR1 (n = 1 SNPs), and SKA2 (n = 1 SNPs) genes, in a sample of 3566 adult outpatients with depression for whom an antidepressant treatment was introduced. General practitioners and psychiatrists throughout France followed participants for 6 weeks after the initial prescription of tianeptine, an antidepressant molecule showing mu agonism. Suicidal ideation was assessed with item 10 of the Montgomery-Åsberg Depression Rating Scale (item dedicated to suicidal ideation) at baseline, and at week 2, 4, and 6 of treatment. Within the informative sample, 112 patients reported TESI and 384 did not. TESI was significantly associated with the TT genotype of the SNP rs6902321 in FKBP5 (OR = 1.76, 95% CI = [1.07; 2.90]; p-value = 0.03) and the GG/AG genotype of the SNP rs7208505 in SKA2 (OR = 1.85, 95% CI = [1.03;3.33]; p-value = 0.04). These associations were not significant after multiple test correction. Nevertheless, our results suggest a possible involvement of HPA axis elements in treatment-emergent suicidal ideation (TESI).

Envelope-Driven Recollisions Triggered by an Elliptically Polarized Pulse.

Increasing ellipticity usually suppresses the recollision probability drastically. In contrast, we report on a recollision channel with large return energy and a substantial probability, regardless of the ellipticity. The laser envelope plays a dominant role in the energy gained by the electron, and in the conditions under which the electron comes back to the core. We show that this recollision channel efficiently triggers various nonlinear and nonperturbative phenomena-such as multiple ionization-with an elliptically polarized pulse.

[Quality of the diagnoses' coding (main or associated diagnoses) in the medico-administrative database for psychiatric care (RIM-P) in 2015 and 2016, France]. / Qualité du codage des diagnostics et motifs de prise en charge (principal et associés) dans le recueil d'informations médicalisé en psychiatrie (RIM-P) en 2015 et 2016, France.

BACKGROUND: Based on the observation of the misuse of ICD-10 to code the diagnoses in the RIM-P (lack of completeness, conformity and diversity), the Technical Agency for information on Hospital Care (ATIH), which provides tools for collecting medical information, conducted two actions in 2016. First, a chapter devoted to the instructions of coding has been written in the methodological guide of production of the RIM-P, second, a variable "type psy" was added to the ICD-10 nomenclature's file framing ICD-10 coding in the RIM-P. The purpose of this study is to describe the quality of diagnosis coding using ICD-10 in the RIM-P in 2015 and 2016. METHODS: The quality of diagnosis coding using ICD-10 in the summaries of activity of the RIM-P national databases was described in 2015 and 2016. The study focused on the completeness, the conformity and the diversity of coding. RESULTS: Between 2015 and 2016, the percentage of summaries without primary diagnosis ("DP") decreased slightly for full-time (5.2% vs. 3.8%), part-time (6.3% vs. 4.9%) inpatient stays and outpatient care (9.9% vs. 8.9%). ICD-10 codes used to code DP or associated diagnosis ("DA"), while prohibited, mainly belong to Chapter V Mental and behavioral disorders. Per year, only one-third of the summaries and one-half of patients had two or more ICD-10 codes reported for inpatient stays (one-fifth of the summaries and one-fourth of the patients for outpatient care). In addition, per year and per facility, the average number of distinct ICD-10 codes used to fill "DP" or "DA" was approximately half as important in part-time hospitalization, as in full-time hospitalization or for outpatient care. Moreover, 90% of the health facilities used<550 distinct ICD-10 codes in full-time inpatient stays,<270 in part-time inpatient stays and<950 for outpatient care to code the "DP" or the "DA". The diversity of ICD-10 codes used was low and similar between 2015 and 2016, especially to describe the socio-economic environment, resistance to treatment or non-compliance. CONCLUSION: This study emphasizes the need for a collective effort to improve the diversity of the diagnoses' coding in the RIM-P.

Vitamin D nutritional status and bone turnover markers in childhood acute lymphoblastic leukemia survivors: A PETALE study.

BACKGROUND: The remarkable progress in the treatment of childhood acute lymphoblastic leukemia (cALL) has led to a survival rate reaching 90%. This success story is unfortunately linked to increased risk of impaired skeletal mass accumulation during childhood and adolescence, predisposing the patients to osteoporosis and pathological fractures at adulthood. OBJECTIVE: This study aims at characterizing the vitamin D status and bone health biomarkers in a well-characterized cohort of cALL survivors. RESULTS: Food frequency questionnaires reveal that (i) the total vitamin D intake varies greatly (44-2132 IU/d), (ii) only 16.8% of the participants consume vitamin D supplements, and (iii) 74% of survivors' intakes are below the Recommended Daily Intakes (400 IU/d). For the 42 participants taking vitamin D supplements, the median (2.5-97.5%iles) intake is 600 IU/d (21.2-1972 IU/d). Sixteen participants are vitamin D deficient (<30 nM) and 66 insufficient (≥30 - <50 nM). Serum 24,25(OH)2D3 concentrations are directly related to those of 25OHD3, and those of 3-epi-25OHD3 below the Lower Limit of Quantification in most samples. The participants' serum concentrations of cross-linked C-telopeptide of type-I collagen and intact amino-terminal pro-peptide of type-I collagen decrease steadily with age, leveling at adulthood, and are at all times higher in males. CONCLUSION: The present study shows that the prevalence of vitamin D insufficiency or deficiency is not greater in cALL survivors compared to the general Canadian population despite low vitamin D food and supplement intakes. Furthermore, there seem to be no overt imbalance in the gender- and age-adjusted serum bone turnover marker concentrations.

Mapping the asynchrony of cortical maturation in the infant brain: A MRI multi-parametric clustering approach.

While the main neural networks are in place at term birth, intense changes in cortical microstructure occur during early infancy with the development of dendritic arborization, synaptogenesis and fiber myelination. These maturational processes are thought to relate to behavioral acquisitions and the development of cognitive abilities. Nevertheless, in vivo investigations of such relationships are still lacking in healthy infants. To bridge this gap, we aimed to study the cortical maturation using non-invasive Magnetic Resonance Imaging, over a largely unexplored period (1-5 post-natal months). In a first univariate step, we focused on different quantitative parameters: longitudinal relaxation time (T1), transverse relaxation time (T2), and axial diffusivity from diffusion tensor imaging (λ//) These individual maps, acquired with echo-planar imaging to limit the acquisition time, showed spatial distortions that were first corrected to reliably match the thin cortical ribbon identified on high-resolution T2-weighted images. Averaged maps were also computed over the infants group to summarize the parameter characteristics during early infancy. In a second step, we considered a multi-parametric approach that leverages parameters complementarity, avoids reliance on pre-defined regions of interest, and does not require spatial constraints. Our clustering strategy allowed us to group cortical voxels over all infants in 5 clusters with distinct microstructural T1 and λ// properties The cluster maps over individual cortical surfaces and over the group were in sound agreement with benchmark post mortem studies of sub-cortical white matter myelination, showing a progressive maturation of 1) primary sensori-motor areas, 2) adjacent unimodal associative cortices, and 3) higher-order associative regions. This study thus opens a consistent approach to study cortical maturation in vivo.

Experimental demonstration of an electromagnetic pulse mitigation concept for a laser driven proton source.

The targets that are used to produce high-energy protons with ultra-high intensity lasers generate a strong electromagnetic pulse (EMP). To mitigate that undesired side effect, we developed and tested a concept called the "birdhouse." It consists in confining the EMP field in a finite volume and in dissipating the trapped electromagnetic energy with an electric resistor. A prototype was tested at a 10 TW 50 fs laser facility. The recorded average EMP mitigation ratio is about 20 for frequencies from 100 MHz to 6 GHz. The EMP mitigation ratio attains the level of 50 in the frequency range of 1-2 GHz where microwave emission is maximal. We measured the intensity of proton emission in two directions: along the laser propagation direction and along the edge of the proton beam. We observed that the "birdhouse" induces a two-fold increase of the intensity in the center of the proton beam and a two-fold reduction of the intensity on its edge. We did not observe any modification of the proton beam normalized spectrum.

Capturing Photoelectron Motion with Guiding Centers.

Electron motion in combined strong laser and Coulomb fields is central to laser-matter interactions. By mapping this problem onto the motion of a guiding center, we derive a reduced model which naturally embeds important Coulomb effects such as focusing and asymmetry, and clearly distinguishes direct versus rescattered electron ionization processes. We demonstrate the power of this tool by unraveling the bifurcation in photoelectron momentum distributions seen in experiments.

A framework based on sulcal constraints to align preterm, infant and adult human brain images acquired in vivo and post mortem.

Robust spatial alignment of post mortem data and in vivo MRI acquisitions from different ages, especially from the early developmental stages, into standard spaces is still a bottleneck hampering easy comparison with the mainstream neuroimaging results. In this paper, we test a landmark-based spatial normalization strategy as a framework for the seamless integration of any macroscopic dataset in the context of the Human Brain Project (HBP). This strategy stems from an approach called DISCO embedding sulcal constraints in a registration framework used to initialize DARTEL, the widely used spatial normalization approach proposed in the SPM software. We show that this strategy is efficient with a heterogeneous dataset including challenging data as preterm newborns, infants, post mortem histological data and a synthetic atlas computed from averaging the ICBM database, as well as more commonly studied data acquired in vivo in adults. We then describe some perspectives for a research program aiming at improving folding pattern matching for atlas inference in the context of the future HBP's portal.

[Knowledge assessment of the coding using CSARR nomenclature, two years after its establishment]. / Bilan de l'appropriation du CSARR, deux ans après sa mise en place.

BACKGROUND: French post-acute care and rehabilitation facilities describe and code their activity through the Program for Medicalization of Information Systems (PMSI). A new specific catalogue of rehabilitation procedures (CSARR) has been implemented to code rehabilitation acts since 2013. This study aimed to assess the coherence of the coding of the rehabilitation acts using the CSARR two years after its establishment through the analyze of 3 main items regarding patients and therapists. METHODS: We analyzed the use of CSARR for coding rehabilitation acts from the PMSI national database for post-acute care and rehabilitation, in 2015. Analyses were made on specific items characterizing rehabilitation acts: "number of patients", "type of therapists" and "number of therapists". RESULTS: There were 72,014,731 rehabilitation acts coded in 2015 using CSARR nomenclature; 86% were individual rehabilitation acts. All acts of CSARR, except one, were used to describe rehabilitation activities. Physiotherapists coded the majority of rehabilitation acts (47%), then nurses (14%). Coding errors were identified as the "number of patients", coded with more than one patient for individual acts (13% of the acts) or with less than 2 patients for groups (6% of the acts), or the "number of therapists" coded with only one therapist for rehabilitation acts requiring several professionals. CONCLUSION: This first assessment indicated a good level of appropriation of the CSARR coding rules in the national PMSI database by post-acute care and rehabilitation facilities. However, a simplification of this catalogue and therapist training could increase the quality of the rehabilitation data.