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"Leurs, Amélie"
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تاريخ العرب العام : إمبراطورية العرب، حضارتهم، مدارسهم الفلسفية والعلمية والأدبية
by
Sédillot, L.-A. (Louis-Amélie), 1808-1875 مؤلف
,
زعيتر، عادل، 1895-1957 معرب
,
Sédillot, L.-A. (Louis-Amélie), 1808-1875. Histoire des Arabes : leur empire, leur civilization, leurs ecoles philosophiques, scientifiques et literatures
in
الحضارة العربية تاريخ
,
الفلك العربي
,
البلاد العربية تاريخ
2020
يتناول الكتاب تاريخ العرب وتاريخ دولتهم من العصر الجاهلي إلى نهاية سقوط دولة العرب في الأندلس وجغرافية دولتهم وحضارتهم ومدارسهم الفلسفية والعلمية والأدبية في الشرق والغرب وفصل كل هذا تفصيلا بين فيه فضل العرب والإسلام على أمم العالم في ميادين العلوم والثقافة والفلسفة والعمران والأدب ونوه بشأنهم في كثير من فصول الكتاب وقدر أثارهم تقديرا حسنا وأثنى عليهم بما هم أهل له، على خلاف الكثير من المستشرقين الذين تناولوا العرب والمسلمين وتاريخهم، فأداروا ظهورهم للدور الكبير الذي لعبه العرب في الحضارة الإنسانية جمعاء.
Prevalence, characteristics, and outcomes of patients with low baseline C-reactive protein in giant cell arteritis
by
Hachulla, Eric
,
Pichon, Samuel
,
Gachet, Benoît
in
Acute phase reactant
,
Aged
,
Aged, 80 and over
2025
Objective
Elevated inflammatory markers play a crucial role in the diagnosis and follow-up of patients with giant cell arteritis (GCA). This study aimed to describe the prevalence, characteristics, and outcomes of patients with low baseline (< 10 mg/L) C-reactive protein (CRP) in GCA.
Methods
A retrospective observational study was conducted at Lille University Hospital, involving all patients diagnosed with GCA between January 2000 and April 2023. Patients were categorized based on their CRP level at diagnosis. Baseline characteristics, clinical manifestations, laboratory findings, imaging results, and outcomes were compared between patients with baseline CRP < 10 mg/L (“low CRP”) and those with CRP ≥ 10 mg/L (“high CRP”).
Results
Of the 380 patients, 7.6% (
n
= 29) had baseline CRP < 10 mg/L at diagnosis. When compared to the high CRP group, the low CRP group exhibited a lower incidence of fever, and had a higher incidence of ocular involvement, particularly anterior ischemic optic neuropathy (28% vs. 13%,
p
= 0.04), and limb claudication (24% vs. 8%,
p
< 0.01). Plasma fibrinogen levels were elevated (> 4 g/L) in 77% of patients with low CRP. Despite differences in clinical presentation, relapse rates were equilibrated between the two groups.
Conclusion
GCA patients with low CRP are not rare and present with more ocular and peripheral vascular involvement and less constitutional symptoms in our study. Elevated fibrinogen in these patients suggests active inflammation despite low CRP. Clinicians should consider GCA even with a CRP < 10 mg/L, as these patients may present with severe complications.
Journal Article
Tolerance and efficacy of targeted therapies prescribed for off-label indications in refractory systemic autoimmune diseases: data of the first 100 patients enrolled in the TATA registry (TArgeted Therapy in Autoimmune Diseases)
by
Saunier, Aurélie
,
Gaigneux, Emeline
,
Quartier, Pierre
in
Adolescent
,
Autoimmune Diseases
,
Autoimmunity
2022
ObjectivesTo assess the tolerance and efficacy of targeted therapies prescribed off-label in refractory low-prevalence autoimmune and inflammatory systemic diseases.MethodsThe TATA registry (TArgeted Therapy in Autoimmune Diseases) is a prospective, observational, national and independent cohort follow-up. The inclusion criteria in the registry are as follows: age >18 years; low-prevalence autoimmune and inflammatory systemic disease treated with off-label drugs started after 1 January 2019.ResultsHundred (100) patients (79 women) were enrolled. The median age was 52.5 years (95% CI 49 to 56) and the median disease duration before enrolment was 5 years (3 to 7). The targeted therapies at enrolment were as follows: Janus kinase/signal transducers and activators of transcription inhibitors (44%), anti-interleukin (IL)-6R (22%), anti-IL-12/23, anti-IL-23 and anti-IL-17 (9%), anti-B cell activating factor of the tumour necrosis factor family (5%), abatacept (5%), other targeted treatments (9%) and combination of targeted treatments (6%). 73% of patients were receiving corticosteroid therapy at enrolment (median dose 10 mg/day). The current median follow-up time is 9 months (8 to 10).Safety: 11 serious infections (incidence rate of 14.8/100 patient-years) and 1 cancer (1.3 cancers/100 patient-years) were observed. Two patients died from severe COVID-19 (2.7 deaths/100 patient-years).Efficacy: the targeted treatment was considered effective by the clinician in 56% of patients and allowed, in responders, a median reduction of oral corticosteroids of 15 (9 to 21) mg/day, below 7.5 mg/day in 76% of patients, while 28% discontinued.ConclusionThese initial results of the TATA registry confirm the diversity of targeted treatments prescribed off-label in refractory autoimmune diseases and their corticosteroid-sparing effect when effective. Tolerance was acceptable in these refractory patients with a long history of treatment with immunosuppressive drugs.
Journal Article
Immune checkpoint inhibitors-associated cranial nerves involvement: a systematic literature review on 136 patients
by
Pichon, Samuel
,
Launay, David
,
Levy, Clémentine
in
Abducens nerve
,
Adverse events
,
Case reports
2024
Objective
Describe the demographic data and clinical phenotype of cranial palsy induced by immune checkpoint inhibitors (CNP-ICI).
Methods
A systematic literature review of the literature was performed in Pubmed, Web of Science, and Embase, including 68 articles and 136 patients (PROSPERO no. CRD42024517262).
Results
Out of the 1205 articles screened, 68 articles were included after fulfilling the inclusion criteria, for a total of 136 patients. All articles were case reports and case series. In the cohort studied, 52% of patients were treated with anti PD-1/PDL-1 therapies, 14% with anti CTLA-4 therapies, and 34% with a combination of anti CTLA-4 and anti PD-1/PDL-1 therapies. The facial nerve was the most affected cranial nerve, involved in 38% of cases, followed by the optic nerve (35%), the cochleovestibular nerve (12%), and the abducens nerve (10%). The median time from the initial immune checkpoint inhibitor (ICI) injection to the onset CNP-ICI was 10 weeks (IQR 4–20). Magnetic resonance imaging demonstrated contrast enhancement or abnormal signal of the affected nerve in 43% of cases. Cerebrospinal fluid analysis indicated lymphocytic pleocytosis in 59% of cases. At the onset of immune-related adverse events, 89% of patients discontinued immunotherapy, and 92% received treatment for CNP-ICI. Treatment regimens included corticosteroids in 86% of cases, intravenous immunoglobulin in 21%, and plasma exchange in 5.1%. Among the whole population, 33% achieved recovery, 52% showed clinical improvement, 16% remained stable, and 3% experienced worsening of their condition. Rechallenge with immunotherapy was significantly associated with the emergence of new immune-related Adverse Events (irAEs).
Conclusion
ICI therapy may lead to cranial nerve involvement, particularly affecting the facial nerve, typically presenting around 10 weeks after treatment initiation. While corticosteroid therapy often resulted in patient improvement, rechallenging with ICIs were associated with new irAEs.
Journal Article
Renal Pathologic Findings in TAFRO Syndrome: Is There a Continuum Between Thrombotic Microangiopathy and Membranoproliferative Glomerulonephritis? A Case Report and Literature Review
2019
TAFRO syndrome is a clinical subtype of idiopathic multicentric Castleman disease (iMCD) that is characterized by thrombocytopenia, anasarca, fever and/or elevated serum C-reactive protein, renal dysfunction, and organomegaly.
A 28-year-old woman with fever, weight gain of 13 kgs, lower extremity edema, hepatosplenomegaly, and multicentric peripheral lymphadenopathy was referred to our center. Laboratory investigations revealed anemia, thrombocytopenia, creatinine at 1.19 mg/dL and hypoalbuminemia at 33 g/L. Proteinuria was measured at 2 g/day including albuminuria at 1.5 g/day. Urinary sediment examination found leukocyturia at 44,000/mL and hematuria at 645,000/mL. Vascular endothelial growth factor (VEGF) level was elevated. A cervical lymph node biopsy found features consistent with the mixed histopathological subtype of iMCD. A renal biopsy revealed a membranoproliferative glomerulonephritis (MPGN) pattern. We initiated 3 days of methylprednisolone pulse-therapy at 1,000 mg per day, followed by prednisone 1 mg/kg/day and evolution was favorable.
19 iMCD patients with TAFRO syndrome had undergone a renal biopsy: 8 cases with author's diagnosis consistent with MPGN-like and 11 cases of thrombotic microangiopathy (TMA)-like glomerulopathy without fibrin thrombi in glomerular capillaries or arterioles and without typical biological signs. Clinical, biological, and outcome characteristics were similar between the cases described as having MPGN and TMA-like presentation. After a thorough review of histopathological descriptions for each case, MPGN lesions seems to be the consequences of chronic glomerular endothelial injury in persistent TMA. We suspect that VEGF and IL-6 play a key role in the physiopathology of the spectrum of renal involvement from TMA-like to MPGN observed in TAFRO syndrome.
We present a Caucasian iMCD patient with TAFRO syndrome with renal insufficiency secondary to MPGN, which might be secondary to a chronic TMA-like disease. We suspect that there is a continuum between TMA and MPGN lesions in TAFRO syndrome favored by VEGF and IL-6.
Journal Article
Factors associated with disease flare following SARS-CoV-2 vaccination in people with inflammatory rheumatic and musculoskeletal diseases: results from the physician-reported EULAR Coronavirus Vaccine (COVAX) Registry
2024
ObjectivesTo investigate the frequency and factors associated with disease flare following vaccination against SARS-CoV-2 in people with inflammatory/autoimmune rheumatic and musculoskeletal diseases (I-RMDs).MethodsData from the European Alliance of Associations for Rheumatology Coronavirus Vaccine physician-reported registry were used. Factors associated with flare in patients with I-RMDs were investigated using multivariable logistic regression adjusted for demographic and clinical factors.ResultsThe study included 7336 patients with I-RMD, with 272 of 7336 (3.7%) experiencing flares and 121 of 7336 (1.6%) experiencing flares requiring starting a new medication or increasing the dosage of an existing medication. Factors independently associated with increased odds of flare were: female sex (OR=1.40, 95% CI=1.05 to 1.87), active disease at the time of vaccination (low disease activity (LDA), OR=1.45, 95% CI=1.08 to 1.94; moderate/high disease activity (M/HDA), OR=1.37, 95% CI=0.97 to 1.95; vs remission), and cessation/reduction of antirheumatic medication before or after vaccination (OR=4.76, 95% CI=3.44 to 6.58); factors associated with decreased odds of flare were: higher age (OR=0.90, 95% CI=0.83 to 0.98), non-Pfizer/AstraZeneca/Moderna vaccines (OR=0.10, 95% CI=0.01 to 0.74; vs Pfizer), and exposure to methotrexate (OR=0.57, 95% CI=0.37 to 0.90), tumour necrosis factor inhibitors (OR=0.55, 95% CI=0.36 to 0.85) or rituximab (OR=0.27, 95% CI=0.11 to 0.66), versus no antirheumatic treatment. In a multivariable model using new medication or dosage increase due to flare as the dependent variable, only the following independent associations were observed: active disease (LDA, OR=1.47, 95% CI=0.94 to 2.29; M/HDA, OR=3.08, 95% CI=1.91 to 4.97; vs remission), cessation/reduction of antirheumatic medication before or after vaccination (OR=2.24, 95% CI=1.33 to 3.78), and exposure to methotrexate (OR=0.48, 95% CI=0.26 to 0.89) or rituximab (OR=0.10, 95% CI=0.01 to 0.77), versus no antirheumatic treatment.ConclusionI-RMD flares following SARS-CoV-2 vaccination were uncommon. Factors associated with flares were identified, namely higher disease activity and cessation/reduction of antirheumatic medications before or after vaccination.
Journal Article
SARS-CoV-2 vaccine safety in adolescents with inflammatory rheumatic and musculoskeletal diseases and adults with juvenile idiopathic arthritis: data from the EULAR COVAX physician-reported registry
2022
BackgroundThere is a lack of data on SARS-CoV-2 vaccination safety in children and young people (CYP) with rheumatic and musculoskeletal diseases (RMDs). Current vaccination guidance is based on data from adults with RMDs or CYP without RMDs.ObjectivesTo describe the safety of SARS-COV-2 vaccination in adolescents with inflammatory RMDs and adults with juvenile idiopathic arthritis (JIA).MethodsWe described patient characteristics, flares and adverse events (AEs) in adolescent cases under 18 with inflammatory RMDs and adult cases aged 18 or above with JIA submitted to the European Alliance of Associations for Rheumatology COVAX registry.ResultsA total of 110 cases were reported to the registry. Thirty-six adolescent cases were reported from four countries, most with JIA (42%). Over half (56%) reported early reactogenic-like AEs. One mild polyarthralgia flare and one serious AE of special interest (malaise) were reported. No CYP reported SARS-CoV-2 infection postvaccination.Seventy-four adult JIA cases were reported from 11 countries. Almost two-thirds (62%) reported early reactogenic-like AEs and two flares were reported (mild polyarthralgia and moderate uveitis). No serious AEs of special interest were reported among adults with JIA. Three female patients aged 20–30 years were diagnosed with SARS-CoV-2 postvaccination; all fully recovered.ConclusionsThis is an important contribution to research on SARS-CoV-2 vaccine safety in adolescents with RMDs and adults with JIA. It is important to note the low frequency of disease flares, serious AEs and SARS-CoV-2 reinfection seen in both populations, although the dataset is limited by its size.
Journal Article
The Translocation Domain of Botulinum Neurotoxin A Moderates the Propensity of the Catalytic Domain to Interact with Membranes at Acidic pH
by
ANR-11-IDEX-0003,IPS,Idex Paris-Saclay
,
Goudet, Amélie
,
Pérez, Javier
in
Acidification
,
Bacteria
,
Biochemistry
2016
Botulinum neurotoxin A (BoNT/A) is composed of three domains: a catalytic domain (LC), a translocation domain (H N) and a receptor-binding domain (H C). Like most bacterial toxins BoNT/A is an amphitropic protein, produced in a soluble form that is able to interact, penetrate and/or cross a membrane to achieve its toxic function. During intoxication BoNT/A is internalized by the cell by receptor-mediated endocytosis. Then, LC crosses the membrane of the endocytic compartment and reaches the cytosol. This translocation is initiated by the low pH found in this compartment. It has been suggested that LC passes in an unfolded state through a transmembrane passage formed by H N. We report here that acidification induces no major conformational change in either secondary or tertiary structures of LC and H N of BoNT/A in solution. GdnHCl-induced denaturation experiments showed that the stability of LC and H N increases as pH drops, and that H N further stabilizes LC. Unexpectedly we found that LC has a high propensity to interact with and permeabilize anionic lipid bilay-ers upon acidification without the help of H N. This property is downplayed when LC is linked to H N. H N thus acts as a chaperone for LC by enhancing its stability but also as a moderator of the membrane interaction of LC.
Journal Article