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Background: The objective of this study was to assess the likelihood of acute appendicitis (AA) in children presenting with abdominal symptoms at the emergency department (ED), based on their prior primary care (PC) consultation history., Methods: Between February and June 2021, we prospectively enrolled all children presenting at the ED with acute abdominal pain indicative of possible acute appendicitis (AA). Subsequently, they were categorized into three groups: those assessed by a PC physician (PG), those brought in by their family without a prior consultation (FG), and those admitted after a PC consultation without being assessed as such. The primary objective was to assess the probability of AA diagnosis using the Pediatric Appendicitis Score (PAS). Secondary objectives included analyzing PAS and C-reactive protein (CRP) levels based on the duration of pain and final diagnoses., Results: 124 children were enrolled in the study (PG, n = 56; FG, n = 55; NG, n = 13). Among them, 29 patients (23.4%) were diagnosed with AA, with 13 cases (23.2%) from the PG and 14 cases (25.4%) from the FG. The mean PAS scores for AA cases from the PG and FG were 6.69 ± 1.75 and 7.57 ± 1.6, respectively, (p = 0.3340). Both PAS scores and CRP levels showed a significant correlation with AA severity. No cases of AA were observed with PAS scores < 4., Conclusions: There was no significant difference in PAS scores between patients addressed by PG and FG, even though PAS scores tended to be higher for patients with AA. We propose a new decision-making algorithm for PC practice, which incorporates inflammatory markers and pain duration., Trial Registration: Institutional Ethics Committee registration number: 447-2021-103 (10/01/2021)., Clinical Trials Registration Number: ClinicalTrials.gov Identifier: NCT04885335 (Registered on 13/05/2021)., (© 2024. The Author(s).)

Objectives: To identify subgroups of people with distinct frailty trajectories, identify baseline characteristics associated with these trajectories, and determine their coincident clinical outcomes., Design: This study examined the longitudinal database from the FREEDOM Cohort Study., Setting and Participants: All 497 participants of the FREEDOM (French Acronym for "FRagilitéEtEvaluation àDOMicile" / In English "Frailty and Evaluation at Home") cohort requested a comprehensive geriatric assessment. Community-dwelling subjects over 75 years, or over 65 years with at least two comorbidities were included., Methods: Frailty was assessed using Fried's criteria, depression using the Geriatric Depression Scale (GDS) and cognitive function using the Mini Mental State Examination (MMSE) questionnaire. Frailty trajectories were modelled using k-means algorithms. Predictive factors were determined by multivariate logistic regression. Clinical outcomes included incident cognitive deficit, falls and hospitalization., Results: The trajectory models allowed determine four frailty trajectories: "robust stable" (Trajectory A, 26.8%), "pre-frail worsening to frailty" (Trajectory B, 35.8%), "frail improving to less frailty" (Trajectory C, 23.3%), and "frail worsening to more frailty" (Trajectory D, 14.1%). Trajectory B was associated with age (OR 1.2 (95CI, 1.05 - 1.17)), potential cognitive deficit/dementia (OR 2.01 (95CI, 1.01- 4.05)) and depressive symptoms (OR 2.36 (95CI, 1.36 - 4.12)). Hypertension was distinguishing factor between" trajectory B vs. C and D. Depressive symptoms were two time more associated with D (OR 10.51) vs. C (OR 4.55). The incidence of clinical outcomes was significantly increased in poor frailty trajectories., Conclusions and Implications: This study allowed to determine frailty trajectories among older subjects requested a comprehensive geriatric assessment. The more significant predictive factors associated with poor frailty trajectory were advanced in age, potential cognitive deficit/dementia, depressive symptoms and hypertension. This emphasizes the need for adequate measures to controlled hypertension, depressive symptoms and to maintain or improve cognition in older adults., Competing Interests: Declaration of Competing Interest The authors declare no competing interests., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Frailty is a geriatric syndrome associated with disability and negative health outcome. To determine the factors associated with frailty and functional disability in older participants living in community in France. We included 753 community-dwelling old participants with available frailty data at baseline., Results: Overall, 31.9% were frail, 58.3% were prefrail, and 9.8% were robust. The SMAF (French acronym for Functional Autonomy Measurement System) score was significantly lower (mean ± standard deviation: -25.8 ± 11.2) in frail participants compared to prefrail (-14.3 ± 9.7) or robust participants (-8.1 ± 7.0); 82% of frail older participants had limitation in at least one ADL and 97.5% in at least one IADL compared to 54.2 and 76.8%, respectively of pre-frail and 29.7 and 47.3% of robust participants. Age, depression, impaired cognition and diabetes were significantly associated with higher odds of frailty. These variables were also strongly associated with functional disability. Female gender, polypharmacy, and smoking were additional variables significantly associated with degraded SMAF and/or ADL/IADL., Conclusions: This study showed that functional disability increased proportionally to frailty, and depression, cognitive decline and diabetes are modifiable risk factors significantly associated with frailty and functional disability., (© 2022. The Author(s).)

Background: Monitoring frailty indicators in elderly people is recommended to identify those who could benefit from disability prevention programs. To contribute to the understanding of the development of frailty in the elderly, we have created the FREEDOM-LNA cohort constituting an observational study of ageing in general population. Here, we described the characteristics of a cohort of elderly subjects who are followed for determination of frailty and loss of independence trajectories., Results: The cohort was composed of 1085 subjects in advanced age (mean: 83.7 ± 6.0 years) and of women in majority (68.3%). Cardiovascular risk factors were present in 88.4% of subjects. Abnormal musculoskeletal signs were reported in 44.0% and neurologic signs in 31.9%. There were 44.8% of subjects at risk of malnutrition (MNA <24) and 73.3% (668/911) at risk of mobility-related disability (SPPB ≤9); 39% (384/973) of subjects had impaired cognitive function (MMSE< 24, adjusted on education) and 49.0% (397/810) had signs of depression (GDS >9); 31.8% (240/753) were frail and 58.3% were pre-frail. Most subjects had at least one disability in ADL (66.9%) and IADL (85.1%). The SMAF indicated a loss of independence in 59.6%. Overall, 59.9% of subjects could not stay at home without at least some help. Consequently, a medical consultation was proposed in 68.2 and 42.1% social supports., Conclusions: A large part of this cohort was frail or pre-frail and presented signs of loss of independence, which may be explained by multiple factors including impaired health status, poor physical performance, cognition, isolation, depression, or nutrition. This cohort will help to determine factors that adversely influence the trajectory of physical frailty over time., (© 2022. The Author(s).)

Objectives: To characterize lymphocytes dysregulation in patients with granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA)., Methods: Using flow cytometry, we analysed B- and T-cell subsets in peripheral blood from 37 untreated patients with active disease (29 GPA and 8 MPA) and 22 healthy controls (HCs)., Results: GPA patients had increased Th2 (1.8 vs 1.0%, P = 0.02), Th9 (1.1 vs 0.2%, P = 0.0007) and Th17 (1.4 vs 0.9%, P = 0.03) cells compared with HC. Patients with MPO-ANCAs had significantly more CD21- B cells than HC or PR3-ANCA patients (6.9 vs 3.3% and 4.4%, P = 0.01). CD69 expressing B cells were significantly higher in GPA and MPA (3.0 and 5.9 vs 1.4%, P = 0.02 and P = 0.03, respectively) compared with HC, whereas B-cell activating factor-receptor expression was decreased in GPA and MPA (median fluorescence intensity ratio 11.8 and 13.7 vs 45.1 in HC, P < 0.0001 and P = 0.003, respectively). Finally, IL-6-producing B cells were increased in GPA vs HC (25.8 vs 14.9%, P < 0.0001) and decreased in MPA vs HC (4.6 vs 14.9%, P = 0.005), whereas TNF-α-producing B cells were lower in both GPA and MPA patients compared with controls (15 and 8.4 vs 30%, P = 0.01 and P = 0.006, respectively)., Conclusion: Skewed T-cell polarization towards Th2, Th9 and Th17 responses characterizes GPA, whereas B-cell populations are dysregulated in both GPA and MPA with an activated phenotype and a decreased B-cell activating factor-receptor expression. Finally, inflammatory B cells producing IL-6 are dramatically increased in GPA, providing an additional mechanism by which rituximab could be effective., (© The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Purpose: Systemic sclerosis (SSc) is characterized by autoimmunity, vasculopathy and fibrosis. Fibrosis is due to an activation of fibroblasts by the transforming growth factor-ß (TGF-ß). This study investigates the proteomic response of SSc fibroblasts to TGF-ß., Experimental Design: Skin fibroblasts from diffuse SSc patients and healthy controls (HC) are cultured with or without TGF-ß. Two-dimensional differential in-gel electrophoresis and mass spectrometry (MS) combined with Ingenuity Pathway analysis (IPA) and Panther/David software analyze proteins differentially expressed between groups. Real-time cell analyzer (RTCA) assesses fibroblast proliferation and viability., Results: Two-hundred-and-seventy-nine proteins are differentially expressed between groups. Principal component analysis shows significant differences between groups. IPA shows specific process networks such as actin cytoskeleton and integrin signaling. Panther and David software show predominant biological processes such as cellular and metabolic processes. TGF-ß enhances protein synthesis and protein pathways. IPA and RTCA suggest the involvement of epidermal growth factor receptor (EGFR) and phosphatidylinositol 3 kinase (Pi3K)., Conclusions and Clinical Relevance: That the proteome of fibroblasts differs between SSc patients and HC is confirmed, and it is demonstrated that fibroblasts exacerbate their proteomic phenotype upon stimulation with TGF-ß. EGFR and Pi3K are highlighted as proteins of interest in SSc fibroblasts., (© 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Objective: To study the role of B lymphocytes in systemic sclerosis (SSc)., Methods: Peripheral B cell subpopulations and the production of interleukin-6 (IL-6) and transforming growth factor β (TGFβ) were analyzed using flow cytometry and multiplex assay. The fibroblast proliferation rate upon incubation with supernatants from B cells isolated from SSc patients or healthy controls was assessed using XTT, bromodeoxyuridine, and Ki-67. Collagen production was assessed using a collagen assay., Results: Ninety untreated patients (12 males) fulfilling the American College of Rheumatology/European League Against Rheumatism criteria for SSc (23 with diffuse cutaneous SSc [dcSSc] and 67 with limited cutaneous SSc [lcSSc]) and 30 healthy controls were recruited. Increased proportions of B cells expressing CD69 and CD95 were identified among the patients with SSc. B lymphocytes from dcSSc patients versus lcSSc patients and healthy controls expressed increased proportion of cells positive for CD5 (mean ± SD 24.12 ± 7.93% versus 14.09 ± 6.58% [P = 0.03] and 14.21 ± 5.34% [P = 0.01]), CD86 (39.89 ± 22.11% versus 17.72 ± 13.98% [P = 0.0007] and 11.68 ± 11.09% [P < 0.001]), IL-6 receptor (IL-6R; 33.64 ± 23.12% versus 17.91 ± 13.62% [P < 0.0001] and 12.08 ± 8.68% [P = 0.0009]), or IL-21R (32.55 ± 20.19% versus 5.76 ± 4.40% [P < 0.0001] and 5.93 ± 3.29% [P < 0.0001]). In addition, the levels of IL-6 (mean ± SD 314.3 ± 317.8 pg/ml versus 6.10 ± 2.58 pg/ml; P = 0.0007) and TGFβ (mean ± SD 1,020 ± 569 pg/ml versus 163.8 ± 98.69 pg/ml; P = 0.001) secreted by B lymphocytes from patients with SSc were increased compared to healthy controls. Fibroblast proliferation and collagen production were also significantly increased in the presence of B cell supernatant from SSc patients as compared to healthy controls., Conclusion: The numbers of activated B cells were increased in SSc patients, and the up-regulation of CD5, CD86, IL-6R, and IL-21R discriminated between patients with dcSSc and those with lcSSc. Peripheral B lymphocytes from SSc patients secreted both IL-6 and TGFβ, and they activated fibroblasts in vitro., (© 2016, American College of Rheumatology.)

ANCA-associated vasculitis (AAV) is a subgroup of vasculitides characterized by the detection of anti-neutrophil cytoplasm antibodies (ANCA). Until recently, the pathogenesis of AAV mainly involved neutrophils, T cells, and ANCA. Importantly, data were recently published supporting B-cell implication in this setting. Thus, the identification of activated B lymphocytes in granulomatous lesions and the efficacy of B-cell depletion using rituximab in the treatment of patients with AAV changed our mind. However, the impact of B lymphocytes on disease activity and its specific role in the pathogenesis of AAV remains unclear, at least in part as the consequence of the limited number of patients investigated and the restricted number of studies investigating B-cell subsets. Perturbations of B-cell homeostasis have been identified in AAV with increased expression of CD38 and decreased expression of CD5 in active phase, contrasting with increased expression of CD25 and CD86 in remission state. Although decreased secretion of interleukin (IL)-10 has also been reported during disease flares, these data remain controversial and the cytokines secretion profile of B-cells needs to be further investigated. Herein, we summarize recent advances in the understanding of the implications of B-cells in the field of AAV and propose new fields of investigation for a better understanding of B lymphocytes in the pathogenesis of AAV., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Major work has been done in order to improve the understanding of systemic sclerosis (SSc) pathogenesis. A number of new experimental models have been set up, that should help to understand the disease pathogenesis and test new therapeutic targets. Reactive oxygen species represent a hallmark of the pathogenesis of SSc, both at the fibroblast and at the endothelial cell levels. Although a large number of genetic studies have been conducted, it is still difficult to identify a genetic background specific to SSc, and the major progress in this setting is probably the identification of an interferon signature. Besides endothelial cells and fibroblasts, major development has been made in the understanding of the role of B cells and autoantibodies in the pathogenesis of SSc. Plasmacytoid dendritic cells seem to play a major role in the pathogenesis of SSc through the secretion of CXCL4, although these data will need to be confirmed in the near future., (Copyright © 2014 Elsevier Masson SAS. All rights reserved.)

Background: Alzheimer's disease (AD) causes progressive loss of memory and disability, especially in older people. As worldwide population grows older, AD is responsible for an important social and economical burden in many nations. People suffering from AD may experience health-related stigma that influences their attitudes towards seeking assistance. The STIG-MA survey describes perceived stigma against AD in a French population., Methods: The STIG-MA questionnaire was completed anonymously by people attending an awareness campaign about AD in Creuse, France, in September 2010. Participants answered 10 questions about how they would feel or react if they had AD. Stigma scores were compared by age, activity, and interest in AD., Results: Thirty-three percent of people attending the campaign filled out the survey. Most were women (85%) younger than 50 years (59%); 10% were older people (older than 75 years). Twenty-one percent worked in health or social fields. Interest in AD was professional (48%), related to family (41%), or personal (11%). Professionals in health fields expressed the highest levels of stigma (p = 0.02). Low stigma was most frequent in older people (p = 0.05). Type of interest did not influence stigma. Shame, loss of self-esteem, and fear of exclusion were expressed the most., Conclusion: The STIG-MA survey confirms that AD is a stigmatizing condition in France. The difference between perceived stigma of older people, those most exposed to AD, and that of health professionals may influence attitudes towards screening and care. Further studies of perceived stigma in these populations are necessary to adapt intervention strategies., (Copyright © 2012 John Wiley & Sons, Ltd.)