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41.
42.
G Taieb C Duflos D Renard B Audoin E Kaphan J Pelletier N Limousin C Tranchant S Kremer J de Sèze R Lefaucheur D Maltête D Brassat M Clanet P Desbordes E Thouvenot L Magy T Vincent JL Faillie N de Champfleur G Castelnovo S Eimer DF Branger E Uro-Coste P Labauge 《Archives of neurology》2012,69(7):847-855
BACKGROUND Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) is a central nervous system inflammatory disease. OBJECTIVE To describe the disease course of CLIPPERS. DESIGN A nationwide study was implemented to collect clinical, magnetic resonance imaging, cerebrospinal fluid, and brain biopsy specimen characteristics of patients with CLIPPERS. SETTING Academic research. PATIENTS Twelve patients with CLIPPERS. MAIN OUTCOME MEASURES The therapeutic management of CLIPPERS was evaluated. RESULTS Among 12 patients, 42 relapses were analyzed. Relapses lasted a mean duration of 2.5 months, manifested frequent cerebellar ataxia and diplopia, and were associated with a mean Expanded Disability Status Scale (EDSS) score of 4. Besides typical findings of CLIPPERS, magnetic resonance imaging showed brainstem mass effect in 5 patients, extensive myelitis in 3 patients, and closed ring enhancement in 1 patient. Inconstant oligoclonal bands were found on cerebrospinal fluid investigation in 4 patients, with an increased T-cell ratio of CD4 to CD8. Among 7 available brain biopsy specimens, staining was positive for perivascular CD4 T lymphocytes in 5 samples. Thirty-eight of 42 relapses were treated with pulse corticosteroid therapy, which led to improvement, with a mean residual EDSS score of 1.9 (range, 0-7). In 1 patient with untreated relapses, scores on the EDSS progressively increased to a score of 10 at death. Among 5 patients without long-term corticosteroid therapy, the mean annualized relapse rate was 0.5 (range, 0.25-2.8). Among 7 patients taking oral corticosteroids, no relapses occurred in those whose daily dose was 20 mg or higher. No progressive course of CLIPPERS was observed. Four patients with a final EDSS score of 4 or higher had experienced previous severe relapses (EDSS score, ≥5) and brainstem and spinal cord atrophy. CONCLUSIONS CLIPPERS is a relapsing-remitting disorder without progressive forms. Long-term disability is correlated with the severity of previous relapses. Further studies are needed to confirm that prolonged corticosteroid therapy prevents further relapses. 相似文献
43.
Brouillette J Caillierez R Zommer N Alves-Pires C Benilova I Blum D De Strooper B Buée L 《The Journal of neuroscience》2012,32(23):7852-7861
Neuronal and synaptic degeneration are the best pathological correlates for memory decline in Alzheimer's disease (AD). Although the accumulation of soluble low-molecular-weight amyloid-β (Aβ) oligomers has been suggested to trigger neurodegeneration in AD, animal models overexpressing or infused with Aβ lack neuronal loss at the onset of memory deficits. Using a novel in vivo approach, we found that repeated hippocampal injections of small soluble Aβ(1-42) oligomers in awake, freely moving mice were able to induce marked neuronal loss, tau hyperphosphorylation, and deficits in hippocampus-dependent memory. The neurotoxicity of small Aβ(1-42) species was observed in vivo as well as in vitro in association with increased caspase-3 activity and reduced levels of the NMDA receptor subunit NR2B. We found that the sequestering agent transthyretin is able to bind the toxic Aβ(1-42) species and attenuated the loss of neurons and memory deficits. Our novel mouse model provides evidence that small, soluble Aβ(1-42) oligomers are able to induce extensive neuronal loss in vivo and initiate a cascade of events that mimic the key neuropathological hallmarks of AD. 相似文献
44.
45.
Nadège Costa Emiel O. Hoogendijk Michael Mounié Robert Bourrel Yves Rolland Bruno Vellas Laurent Molinier Matteo Cesari 《Journal of the American Medical Directors Association》2017,18(5):453.e7-453.e12
Objectives
Pneumonia is a frequent condition in older people. Our aim was to examine the total healthcare cost related to pneumonia in nursing home (NH) residents over a 1-year follow-up period.Design
This was a prospective, longitudinal, observational, and multicenter study that was a part of the Incidence of Pneumonia and related Consequences in Nursing Home Resident study.Setting
Thirteen NHs located in Languedoc Roussillon and Midi-Pyrénées regions in France were included.Participants
Resident in NH, older than 60 years and had a group iso-resource score ranging from 2 to 5.Measurements
Pneumonia events were characterized according to the Observatoire du Risque Infectieux en Geriatrie criteria. Direct medical and nonmedical costs were assessed from the French health insurance perspective. Healthcare resources was retrospectively gathered from the French Social Health Insurance database and valued using the tariffs reimbursed by the French health insurance. Sociodemographic variables, clinical factors, vaccinations, cognition, depression, functional status, frailty index, as well as group iso-resource score were also recorded.Results
Among the 800 patients initially included in the Incidence of Pneumonia and Related Consequences in Nursing Home Resident study, 345 which were listed in the database of the French Social Health Insurance were included in this economic study. Among them, 64 (18%) experienced at least 1 episode of pneumonia during the 1-year follow-up period. Mean annual total additional cost for a patient who experienced at least 1 episode of pneumonia during the 1 year follow-up period is 2813€. On average, total annual costs increased by 60% to 93% when a patient experienced at least 1 episode of pneumonia.Conclusions
NH-acquired pneumonia has a great impact on total cost of care for NH residents. Our results suggest the potential economic savings that could be achieved if pneumonia could be prevented in NHs. 相似文献46.
Frequency and Risk Factors for Associated Lymphomas in Patients With Lymphomatoid Papulosis
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Nadège Cordel Benoît Tressières Michel D'Incan Laurent Machet Florent Grange Éric Estève Sophie Dalac Saskia Ingen‐Housz‐Oro Martine Bagot Marie Beylot‐Barry Pascal Joly for the French Study Group on Cutaneous Lymphoma 《The oncologist》2016,21(1):76-83
Background.
Lymphomatoid papulosis (LyP) is classified as an indolent cutaneous lymphoma, but outcome dramatically worsens if LyP is associated with lymphoma. The frequency of this association remains unclear in the literature. Here, we assess the frequency and risk factors of association between LyP and another lymphoma in an 11-year retrospective study conducted in 8 dermatology departments belonging to the French Study Group on Cutaneous Lymphoma (FSGCL).Patients and Methods.
Patients with LyP were identified and data extracted from the FSGCL registry between 1991 and 2006. Patients were followed up to January 2014. Age, sex, number of skin lesions, histologic subtype, and genotype were recorded at baseline. Risk factors were determined using univariate and multivariate analysis. Cumulative probability of association was calculated using the Kaplan-Meier method.Results.
We observed 52 cases of lymphomas (cutaneous, n = 38; systemic, n = 14) in 44 of 106 patients (41%). Lymphoma diagnosis was concomitant with or prior to LyP diagnosis in 31 cases and occurred during the course of LyP in 21 cases (cutaneous, n = 14; systemic, n = 7; median delay: 5 years; interquartile range: 1.5–7 years). In multivariate analysis, main prognostic factors for association between LyP and another lymphoma were older age (odds ratio [OR]: 1.05 per year; 95% confidence interval [CI]: 1.01–1.08; p = .011) and presence of a T-cell clone in LyP lesions (OR: 7.55; 95% CI: 2.18–26.18; p = .001).Conclusion.
Older age and presence of a T-cell clone in LyP lesions are risk factors for associated lymphomas in patients with LyP. These findings should help to identify patients who require close management in clinical practice.Implications for Practice:
The management of lymphomatoid papulosis (LyP) is that of an indolent cutaneous lymphoma, based on its excellent prognosis. However, this good prognosis is altered if LyP is associated with lymphoma. Furthermore, risk factors for and frequency of this association remain unclear in the literature. The results presented here demonstrate a high rate of association between LyP and other lymphomas (41%) as well as a long median delay of occurrence (5 years), which emphasizes the need for prolonged follow-up of patients with LyP. Moreover, two main risk factors (i.e., older age and presence of a T-cell clone in LyP lesions) are highlighted, which should help clinical practitioners to identify patients who require close management. 相似文献47.
Céline Anquetil Olivier Boyer Nadège Wesner Olivier Benveniste Yves Allenbach 《Autoimmunity reviews》2019,18(3):223-230
Over the past few years, myositis-specific autoantibodies played an increasing role in the inflammatory idiopathic myositis definition. They became the critical immunological marker for immune-mediated necrotizing myopathy diagnosis (IMNM) since the paradigm switch from histological to serological criteria.This review is focused on the key role of the anti-signal recognition particle (anti-SRP) and the anti-3-Hydroxy-3-MethylGlutaryl-Coenzyme A Reductase (anti-HMGCR) antibodies in immune-mediated necrotizing myopathy.Anti-SRP and anti-HMGCR antibodies are robust diagnostic tools in case of both the classical subacute form and the slowly progressive form of IMNM that may mimic muscular dystrophy. Anti-SRP and anti-HMGCR patients share clinical, biological and histological features with some antibody-associated specificity. Anti-SRP patients harbour more severe muscle weakness and atrophy with severe muscle damage on magnetic resonance imaging study. Approximately 10–20% of anti-SRP patients develop extramuscular symptoms, especially lung interstitial disease. Conversely, anti-HMGCR patients are often associated with statin exposure. In both cases, patients have a poor outcome with frequent relapse and the use of combined immunotherapy. Of note, various data suggest a direct pathogenic role of these antibodies reinforcing the interest in targeted therapeutic strategy. 相似文献
48.
Nadège Corbin Nick Todd Karl J. Friston Martina F. Callaghan 《Human brain mapping》2018,39(10):3884-3897
Rapid imaging techniques are increasingly used in functional MRI studies because they allow a greater number of samples to be acquired per unit time, thereby increasing statistical power. However, temporal correlations limit the increase in functional sensitivity and must be accurately accounted for to control the false‐positive rate. A common approach to accounting for temporal correlations is to whiten the data prior to estimating fMRI model parameters. Models of white noise plus a first‐order autoregressive process have proven sufficient for conventional imaging studies, but more elaborate models are required for rapidly sampled data. Here we show that when the “FAST” model implemented in SPM is used with a well‐controlled number of parameters, it can successfully prewhiten 80% of grey matter voxels even with volume repetition times as short as 0.35 s. We further show that the temporal signal‐to‐noise ratio (tSNR), which has conventionally been used to assess the relative functional sensitivity of competing imaging approaches, can be augmented to account for the temporal correlations in the time series. This amounts to computing the t‐score testing for the mean signal. We show in a visual perception task that unlike the tSNR weighted by the number of samples, the t‐score measure is directly related to the t‐score testing for activation when the temporal correlations are correctly modeled. This score affords a more accurate means of evaluating the functional sensitivity of different data acquisition options. 相似文献
49.
Marc Hoonakker Nadège Doignon-Camus José Eduardo Marques-Carneiro Anne Bonnefond 《Clinical neurophysiology》2017,128(9):1599-1607
Objective
The main goal of the current study was to assess, with a time-on-task approach, sustained attention ability in schizophrenia, and to investigate conflict monitoring underlying this ability.Methods
Behavioral and event-related potentials data (N2 and P3a amplitudes) were recorded in a long-lasting sustained attention Go/NoGo task (sustained attention to response task, SART), over a period of 30 min, in 29 patients with schizophrenia and 29 pair-matched healthy subjects.Results
Our results revealed spared sustained attention ability in patients throughout the task. Impairment of conflict detection (N2) in patients was particularly significant at the end of the task. Furthermore, both schizophrenia and healthy subjects exhibited a decline in conflict detection from the beginning to the middle of the task. Whereas controls’ conflict detection recovered in the last part of the task, patients’ did not, suggesting a deficit in recovery processes reflecting a lack of additional resources sustained attention Go/NoGo task. Conflict resolution (P3a) was preserved throughout the task in both groups.Conclusions
Conflict monitoring processes are increasingly impaired in schizophrenia during a long-lasting sustained attention Go/NoGo task.Significance
This impairment at the end of the task may rely on deficit in recovery processes, rather than a deficit in conflict detection per se in schizophrenia. 相似文献50.
Faget J Biota C Bachelot T Gobert M Treilleux I Goutagny N Durand I Léon-Goddard S Blay JY Caux C Ménétrier-Caux C 《Cancer research》2011,71(19):6143-6152
In breast carcinomas, patient survival seems to be negatively affected by the recruitment of regulatory T cells (T(reg)) within lymphoid aggregates by CCL22. However, the mechanisms underpinning this process, which may be of broader significance in solid tumors, have yet to be described. In this study, we determined how CCL22 production is controlled in tumor cells. In human breast carcinoma cell lines, CCL22 was secreted at low basal levels that were strongly increased in response to inflammatory signals [TNF-α, IFN-γ, and interleukin (IL)-1β], contrasting with CCL17. Primary breast tumors and CD45(+) infiltrating immune cells appeared to cooperate in driving CCL22 secretion, as shown clearly in cocultures of breast tumor cell lines and peripheral blood mononuclear cells (PBMC) or their supernatants. We determined that monocyte-derived IL-1β and TNF-α are key players as monocyte depletion or neutralization of these cytokines attenuated secretion of CCL22. However, when purified monocytes were used, exogenous human IFN-γ was also required to generate this response suggesting a role for IFN-γ-producing cells within PBMCs. In this setting, we found that human IFN-γ could be replaced by the addition of (i) IL-2 or K562-activated natural killer (NK) cells or (ii) resting NK cells in the presence of anti-MHC class I antibody. Taken together, our results show a dialogue between NK and tumor cells leading to IFN-γ secretion, which in turn associates with monocyte-derived IL-1β and TNF-α to drive production of CCL22 by tumor cells and subsequent recruitment of T(reg). As one validation of this conclusion in primary breast tumors, we showed that NK cells and macrophages tend to colocalize within tumors. In summary, our findings suggest that at early times during tumorigenesis, the detection of tumor cells by innate effectors (monocytes and NK cells) imposes a selection for CCL22 secretion that recruits T(reg) to evade this early antitumor immune response. 相似文献