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Brain color-coded diffusion imaging: Utility of ACPC reorientation of gradients in healthy subjects and patients
No full textInternational audienceBackground and ObjectiveThe common structural interpretation of diffusion color-encoded (DCE) maps assumes that the brain is aligned with the gradients of the MRI machine. This is seldom achieved in the field, leading to incorrect red (R), green (G) and blue (B) DCE values for the expected orientation of fiber bundles. We studied the virtual reorientation of gradients according to the anterior commissure – posterior commissure (ACPC) system on the RGB derivatives.MethodsWe measured mean ± standard deviation of average, standard deviation, skewness and kurtosis of RGB derivatives, before (rO) and after (acpcO) gradient reorientation, in one healthy-subject group with head routinely positioned (HS-routine), and in two patient groups, one with essential tremor (ET-Opti), and one with Parkinson's disease (PD-Opti), with head position optimized according to ACPC before acquisition. We studied the pitch, roll and yaw angles of reorientation, and we compared rO and acpcO conditions, and groups (ad hoc statistics).ResultsPitch (maximum in the HS-routine group) was greater than roll and yaw. After reorientation of gradients, in the HS-routine group, DCE average increased, and Stddev, skewness and kurtosis decreased; R, G and B average increased, and R and B skewness and kurtosis decreased. By contrast, in the ET-Opti group and the PD-Opti group, R, G and B, average and Stddev increased, and skewness and kurtosis decreased. In both rO and acpcO conditions, in the ET-Opti and PD-Opti groups, average and standard deviation were higher, while skewness and kurtosis were lower.ConclusionsDCE map interpretability depends on brain orientation. Reorientation realigns gradients with the anatomic and physiologic position of the head and brain, as exemplified
Pustular mycosis fungoides has a poor outcome: a multicentric clinico-pathological and molecular case series study
No full textInternational audienceBackground Mycosis fungoides (MF) has usually an indolent course. However, some patients develop a more aggressive disease and few prognostic parameters have been identified. Isolated cases of pustular MF (pMF) suggest an unfavourable prognosis. Objectives We aim to describe the clinico-pathological characteristics and prognostic value of pMF. Methods We retrospectively collected data of all cases of MF with histological pustules diagnosed from 2009 to 2020. The outcomes and clinico-pathological characteristics of pMF at diagnosis (pMFD) were compared to those of a cohort of non-pustular MF (NpMF). Results 33 pMF (including 22 pMFD) and 86 NpMF cases were included. The median age at diagnosis of pMF was 61 years [IQR=50-75]. The median follow-up of pMFD was 32 months [IQR=14-49]. Clinically, 33% of pMF had pustules. Large-cell transformation (LCT) occurred in 17 cases. pMFD were at a significantly more advanced-stage and more showed LCT at diagnosis than NpMF (50% vs 7%, p<0.001 and 23% vs 0%, p<0.001, respectively). In multivariate Cox analysis, the presence of histological pustule at diagnostic was associated with shorter OS in all patients (HR=13.90, CI95%[2.43-79]; p=0.003), and in early-stage patients (HR=11.09, CI95%[1.56-78.82]; p=0.02). In multivariate Fine and Gray model analysis, pMFD was associated with a higher cumulative incidence of LCT (SHR=13.90, CI95% [2.43-79]; p=0.003) in all patients. Median OS after the occurrence of histological pustules during follow-up of all pMF patients was 37 months, with a five-year OS of 25% (CI95% [0.06-0.5]). Conclusion pMF often follows an aggressive course, with a high risk of LCT and shorter survival, even for early-stage patients. Histological pustules at diagnostic of MF might represent an independent poor prognostic factor, to be confirmed by further studies. Because pustules are not always clinically identified, histological pustules should be mentioned in pathology reports of MF and prompt discussion of a closer follow-up
Enseigner les langues en hybride à l’université
No full textBien avant que la crise sanitaire de la COVID-19 ne vienne bouleverser les pratiques d’enseignement et d’apprentissage en forçant la dématérialisation des dispositifs, le Pôle d'Élaboration de Ressources Linguistiques (PERL) de la ComUE USPC, en précurseur, avait déjà exploré, dès 2016, les territoires du numérique dans le cadre de l’enseignement-apprentissage des langues à l’Université. Deux colloques, « Entre présence et distance : enseigner et apprendre les langues à l'université à l'ère du numérique » avaient alors réunis nombre de chercheurs et chercheuses déjà engagés sur ce terrain, en 2017 et en 2019. Ce numéro donne à lire certaines des contributions du colloque de 2019, à l'actualité encore vive. En effet, ces recherches réalisées avant la crise, loin d’être dépassées, offrent au contraire des clefs qui peuvent s’avérer précieuses maintenant que la médiation numérique s’est généralisée. À ce titre, ce numéro témoigne des évolutions imposées par la crise sanitaire et permet un regard réflexif sur les conditions d’implémentation des dispositifs d’enseignement médiatisés
Determinants of Return to Work After a Stroke: A Systematic Review and Meta-analysis
No full textInternational audienceObjective: To identify prognostic factors for return to work (RTW) after stroke. Data Sources: PubMed, MEDLINE, Cochrane, and Embase were systematically searched. Study Selection: Studies had to include people of working age (<65 years old) at the time of stroke (ischemic, hemorrhagic, or subarachnoid hemorrhage). The evaluation of RTW and rate of RTW had to be mentioned. Study selection was done by 2 independent authors. In total, 1241 articles were screened, 39 met all inclusion criteria. Data Extraction: Characteristics of included studies were recorded independently by 2 authors. Differences were resolved through discussion or with a third author. Quality was assessed using the Scottish Intercollegiate Guidelines Network quality assessment tool. Data Synthesis: Among the 39 studies, prognostic factors for RTW were hemorrhagic stroke (odds ratio 0.53 [95% confidence interval 0.45-0.60], independence in activities of daily living (3.99 [1.73-9.23], n=7), and stroke severity (NIHSS) (1.23 [1.08-1.39], n=6). Conclusions: This meta-analysis highlighted positive and negative prognostic factors associated with RTW after stroke. Two categories were distinguished: modifiable and non-modifiable prognostic factors. This study provides information to help understand the issues, set appropriate objectives and implement appropriate strategies to guide people to RTW after stroke. Randomized controlled studies are needed to better evaluate work-place intervention programs as well as the effects of intravenous thrombolysis, and cognitive and neuropsychological rehabilitation on return-to-work rates after stroke. Archives of Physical Medicine and Rehabilitation 2024;105:359-68 (c) 2023 by the American Congress of Rehabilitation Medicine
FLT3L governs the development of partially overlapping hematopoietic lineages in humans and mice
No full textInternational audienceFMS-related tyrosine kinase 3 ligand (FLT3L), encoded by FLT3LG, is a hematopoietic factor essential for the development of natural killer (NK) cells, B cells, and dendritic cells (DCs) in mice. We describe three humans homozygous for a loss-of-function FLT3LG variant with a history of various recurrent infections, including severe cutaneous warts. The patients' bone marrow (BM) was hypoplastic, with low levels of hematopoietic progenitors, particularly myeloid and B cell precursors. Counts of B cells, monocytes, and DCs were low in the patients' blood, whereas the other blood subsets, including NK cells, were affected only moderately, if at all. The patients had normal counts of Langerhans cells (LCs) and dermal macrophages in the skin but lacked dermal DCs. Thus, FLT3L is required for B cell and DC development in mice and humans. However, unlike its murine counterpart, human FLT3L is required for the development of monocytes but not NK cells
Functional diversity of NLRP3 gain-of-function mutants associated with CAPS autoinflammation
No full textInternational audienceNLRP3-associated autoinflammatory disease is a heterogenous group of monogenic conditions caused by NLRP3 gain-of-function mutations. The poor functional characterization of most NLRP3 variants hinders diagnosis despite efficient anti-IL-1 treatments. Additionally, while NLRP3 is controlled by priming and activation signals, gain-of-functions have only been investigated in response to priming. Here, we characterize 34 NLRP3 variants in vitro, evaluating their activity upon induction, priming, and/or activation signals, and their sensitivity to four inhibitors. We highlight the functional diversity of the gain-of-function mutants and describe four groups based on the signals governing their activation, correlating partly with the symptom severity. We identify a new group of NLRP3 mutants responding to the activation signal without priming, associated with frequent misdiagnoses. Our results identify key NLRP3 residues controlling inflammasome activity and sensitivity to inhibitors, and antagonistic mechanisms with broader efficacy for therapeutic strategies. They provide new insights into NLRP3 activation, an explanatory mechanism for NLRP3-AID heterogeneity, and original tools for NLRP3-AID diagnosis and drug development
High-Efficacy Therapy Discontinuation vs Continuation in Patients 50 Years and Older With Nonactive MS
No full textInternational audienceImportance: A recent randomized clinical trial concluded that discontinuing medium-efficacy therapy might be a reasonable option for older patients with nonactive multiple sclerosis (MS), but there is a lack of data on discontinuing high-efficacy therapy (HET). In younger patients, the discontinuation of natalizumab and fingolimod is associated with a risk of rebound of disease activity.Objective: To determine whether discontinuing HET in patients 50 years and older with nonactive MS is associated with an increased risk of relapse compared with continuing HET.Design, setting, and participants: This observational cohort study used data from 38 referral centers from the French MS registry (Observatoire Français de la Sclérose en Plaques [OFSEP] database). Among 84704 patients in the database, data were extracted for 1857 patients 50 years and older with relapsing-remitting MS treated by HET and with no relapse or magnetic resonance imaging activity for at least 2 years. After verification of the medical records, 1620 patients were classified as having discontinued HET or having remained taking treatment and were matched 1:1 using a dynamic propensity score (including age, sex, disease phenotype, disability, treatment of interest, and time since last inflammatory activity). Patients were included from February 2008 to November 2021, with a mean (SD) follow-up of 5.1 (2.9) years. Data were extracted in June 2022.Exposures: Natalizumab, fingolimod, rituximab, and ocrelizumab.Main outcomes and measures: Time to first relapse.Results: Of 1620 included patients, 1175 (72.5%) were female, and the mean (SD) age was 54.7 (4.8) years. Among the 1452 in the HET continuation group and 168 in the HET discontinuation group, 154 patients in each group were matched using propensity scores (mean [SD] age, 57.7 [5.5] years; mean [SD] delay since the last inflammatory activity, 5.6 [3.8] years; mean [SD] follow-up duration after propensity score matching, 2.5 [2.1] years). Time to first relapse was significantly reduced in the HET discontinuation group compared with the HET continuation group (hazard ratio, 4.1; 95% CI, 2.0-8.5; P < .001) but differed between HETs, with a hazard ratio of 7.2 (95% CI, 2.1-24.5; P = .001) for natalizumab, 4.5 (95% CI, 1.3-15.5; P = .02) for fingolimod, and 1.1 (95% CI, 0.3-4.8; P = .85) for anti-CD20 therapy.Conclusion and relevance: As in younger patients, in patients 50 years and older with nonactive MS, the risk of relapse increased significantly after stopping HETs that impact immune cell trafficking (natalizumab and fingolimod). There was no significant increase in risk after stopping HETs that deplete B-cells (anti-CD20 therapy). This result may inform decisions about stopping HETs in clinical practice
Accuracy of conventional impressions and digital scans for implant-supported fixed prostheses in maxillary free-ended partial edentulism: An in vitro study
No full textInternational audienceTo evaluate the accuracy of conventional polyether impressions and digital scans produced by five intra-oral scanners (IOSs) in maxillary free-ended partial edentulism for long-span implant-supported prostheses. Methods: This in vitro study involved the impression of a maxillary model with free-end partial edentulism, in which six implants were placed before digitization using a desktop scanner to generate a digital reference model. Conventional impressions (Impregum Penta Soft, 3M) and digital scans with five IOSs (Trios 3 and 4, 3Shape; Primescan, Dentsply-Sirona; CS 3600, Carestream Dental; and i-500, Medit) were obtained. Conventional impressions were digitized using the same desktop scanner. Each digital STL file of conventional or digital impressions was superimposed over the reference STL file to enable comparison. Trueness was assessed by calculating angles and distance deviations. For precision, dispersions of values around their means were also measured. Results: The mean distance deviation was significantly higher for conventional impressions (454.24 ± 334.70 µm) than for IOSs (ranging from 160.98 ± 204.48 µm to 255.56 ± 395.89 µm) (p < 0.001). The mean angular deviation was high with conventional impressions (1.82 ± 1.51 •), intermediate with CS 3600 (1.38 ± 1.42 •), Primescan (1.37 ± 2.54 •) and Trios 4 (1.30 ± 0.64 •) scanners, and lower with I500 (0.97 ± 0.75 •) and Trios 3 (1.01 ± 0.85 •) scanners (p < 0.001). The dispersion of distance values around their means was lowest with Trios 3 and i-500, followed by CS3600, Primescan, and Trios 4, respectively, and higher for conventional impressions (p < 0.001). The dispersion of angular values was smallest with i-500, Trios 3, and Trios 4 compared with other groups and was highest with Primescan (p < 0.001). Conclusions: Within the limits of the current study, Trios 3 scanner exhibited the highest accuracy, followed by i-500, Trios 4, CS 3600, Primescan, and conventional impressions respectively. IOSs might be reliable for the fabrication of an implant-supported prosthesis. In vivo studies are required to confirm these findings. Clinical significance: Passive adaptation of the implant-supported framework is a challenge when rehabilitating patients with maxillary free-end partial edentulism. While Conventional impressions remain a reliable and validated technique, but IOSs demonstrated higher accuracy, suitable for the fabrication of long-span implantsupported prostheses in partially edentulous arch
Renal replacement therapy initiation strategies in comatose patients with severe acute kidney injury: a secondary analysis of a multicenter randomized controlled trial
No full textInternational audiencePurpose: The effect of renal replacement therapy (RRT) in comatose patients with acute kidney injury (AKI) remains unclear. We compared two RRT initiation strategies on the probability of awakening in comatose patients with severe AKI.Methods: We conducted a post hoc analysis of a trial comparing two delayed RRT initiation strategies in patients with severe AKI. Patients were monitored until they had oliguria for more than 72 h and/or blood urea nitrogen higher than 112 mg/dL and then randomized to a delayed strategy (RRT initiated after randomization) or a more-delayed one (RRT initiated if complication occurred or when blood urea nitrogen exceeded 140 mg/dL). We included only comatose patients (Richmond Agitation-Sedation scale [RASS] + 1). Primary outcome was the transition from coma to awakening during 28 days after randomization.Results: A total of 168 comatose patients (90 delayed and 78 more-delayed) underwent randomization. The transition intensity from coma to awakening was lower in the more-delayed group (hazard ratio [HR] = 0.36 [0.17-0.78]; p = 0.010). Time spent awake was 10.11 days [8.11-12.15] and 7.63 days [5.57-9.64] in the delayed and the more-delayed groups, respectively. Two sensitivity analyses were performed based on sedation status and sedation practices across centers, yielding comparable results.Conclusion: In comatose patients with severe AKI, a more-delayed RRT initiation strategy resulted in a lower chance of transitioning from coma to awakening
Atypical Anti-Glomerular Basement Membrane Nephritis: A Case Series From the French Nephropathology Group
No full textInternational audienceRationale & objective: Atypical anti-glomerular basement membrane (GBM) nephritis is characterized by a bright linear immunoglobulin staining along the GBM by immunofluorescence without a diffuse crescentic glomerulonephritis nor serum anti-GBM antibodies by conventional ELISA. We characterized a series of patients with atypical anti-GBM disease.Study design: Case series.Setting & participants: Patients were identified by the French Nephropathology Group as having atypical anti-GBM nephritis between 2003 and 2022.Findings: Among 38 potential cases, 25 were included. 14 (56%) were female and 23 (92%) had hematuria. Median [interquartile range (IQR)] serum creatinine at diagnosis was 150 [102-203] μmol/L and median [IQR] urine protein to creatinine ratio was 2.4 [1.3-5.2] g/g. 9 (36%) patients had endocapillary proliferative glomerulonephritis (GN), 4 (16%) had mesangial proliferative GN, 4 (16%) had membranoproliferative GN, 2 (8%) had pure and focal crescentic GN, 1 (4%) had focal segmental glomerulosclerosis, and 5 had glomeruli that were unremarkable on histopathology. Nine patients (36%) had crescents, involving a median of 9% of glomeruli. Bright linear staining for IgG was seen in 22 cases (88%) and for IgA in 3 cases (12%). The nine patients (38%) who had a monotypic staining pattern tended to be older with less proteinuria and rarely had crescents. Kidney survival rate at one year was 83% and did not appear to be associated with the light chain restriction.Limitations: Retrospective case series with a limited number of biopsies including electron microscopy.Conclusions: Compared to typical anti-GBM disease, atypical anti-GBM nephritis frequently presents with endocapillary or mesangial proliferative glomerulonephritis pattern and appears to have slower disease progression. Further studies are needed to fully characterize its pathophysiology and associated clinical outcomes