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Objective. Immunoglobulin-G4-(IgG4-) related disease (IgG4 RD) is a fibrosing process characterized by a significant infiltration of IgG4-secreting plasma cells. IgG4 RD can affect almost all organs including salivary glands. Whether IgG4 RD plays a role in the development of sicca syndrome and particularly dry mouth syndrome remains to be investigated. Methods. We conducted a monocentric cohort study for two years to search for IgG4 RD features in patients with dry mouth syndrome using immunostainings of labial salivary gland specimens with anti-IgG4 antibody. Results. Among 60 patients presenting with dry mouth syndrome who underwent labial salivary gland biopsy, 18 showed positive immunostaining with the anti-IgG4 antibody including 4 patients with typical systemic IgG4 RD. Five also fulfilled criteria for Sjögren's syndrome. Conclusion. These findings suggest that clinical forms of IgG4 RD salivary involvement without salivary swelling may occur. This salivary involvement is probably overlooked in everyday practice and could represent a mild form of IgG4 RD. [ABSTRACT FROM AUTHOR]

Abstract Background Non-brucellar and non-tuberculous infectious sacroiliitis (ISI) is a rare disease, with misleading clinical signs that delay diagnosis. Most observations are based on isolated case reports or small case series. Our aim was to describe the clinical, bacteriological, and radiological characteristics of ISI, as well as the evolution of these arthritis cases under treatment. Methods This retrospective study included all ISI cases diagnosed between 1995 and 2011 in eight French rheumatology departments. ISI was diagnosed if sacroiliitis was confirmed bacteriologically or, in the absence of pathogenic agents, if clinical, biological, and radiological data was compatible with this diagnosis and evolution was favourable under antibiotic therapy. Results Overall, 39 cases of ISI were identified in adults, comprising 23 women and 16 men, with a mean age at diagnosis of 39.7 ± 18.1 years. The left sacroiliac joint (SI) was affected in 59% of cases, with five cases occurring during the post-partum period. Lumbogluteal pain was the most common symptom (36/39). Manipulations of the SI joint were performed in seven patients and were always painful. Mean score for pain using the visual analogue score was 7.3/10 at admission, while 16 patients were febrile at diagnosis. No risk factor was found for 30.7% of patients. A diagnosis of ISI was only suspected in five cases at admission. The mean time to diagnosis was long, being 43.3 ± 69.1 days on average. Mean C-reactive protein was 149.7 ± 115.3 mg/l, and leukocytosis (leukocytes ≥ 10 G/l) was uncommon (n = 15) (mean level of leukocytes 10.4 ± 3.5 G/l). Radiographs (n = 33) were abnormal in 20 cases, revealing lesions of SI, while an abdominopelvic computed tomography (CT) scan (n = 27) was abnormal in 21 cases, suggesting arthritis of the SI joints in 13 cases (48.1%) and a psoas abscess in eight. Bone scans (n = 14) showed hyperfixation of the SI in 13 cases. Magnetic resonance imaging (MRI) (n = 27), when focused on the SI (n = 25), directed towards the diagnosis to ISI in 25 cases. Pathogenic agents were isolated in 33 cases (84.6%) by means of articular puncture (n = 16), blood culture (n = 14), cytobacteriological examination of urine (n = 2), or puncture of the psoas (n = 1). Gram-positive cocci were the mostly isolated common bacteria, with a predominance of staphylococci (n = 21). The most frequently isolated gram-negative bacillus was Pseudomonas aeruginosa (n = 3). Evolution was favourable in 37 out of 39 patients under prolonged antibiotic therapy (mean duration 3.01 ± 1.21 months). Conclusion Our series confirmed that the clinical manifestations of ISI usually lead to delayed diagnosis. Based on our results, we suggest performing an MRI of the spine and SI in clinical situations characterised by lumbogluteal pain and symptoms of an infectious disease, such as fever.

La crise rénale est une manifestation sévère de la sclérodermie systémique [1] , dont le pronostic est sombre. Il s'agit d'une étude descriptive monocentrique rétrospective, qui rapporte les facteurs de risques, les caractéristiques et les modalités de traitement chez 6 patients, suivis dans un service de médecine interne, d'un centre hospitalier universitaire, ayant eu une crise rénale sclérodermique entre 2010 et 2019 selon les critères décrits par Steen en 2003 et repris par le protocole national de diagnostic et de soins. Les patients répondent tous aux critères ACR/EULAR de sclérodermie systémique. Les données sont issues du dossier informatisé. La série était composée de 5 femmes pour 1 homme. Les patients étaient âgés de 38 à 72 ans. Quatre patients avaient une sclérodermie systémique diffuse et 2 avaient une sclérodermie systémique limitée. Deux avaient des anticorps anti-ARN-polymérase III, 2 des anticorps anti-Scl-70, 1 des anticorps anticentromères et 1 des anticorps anti-nucléole. Le score de Rodnan modifié, au moment de la crise, était compris entre 8 et 46. Une patiente avait des antécédents de carcinome canalaire infiltrant et était porteuse de prothèses mammaires. Une patiente était sous 10 mg de Cortancyl au moment de la crise. Aucun patient n'avait consommé une corticothérapie supérieure à 15 milligrammes par jour dans les 3 mois précédant le diagnostic. Un patient était sous inhibiteurs de l'enzyme de conversion, arrêté peu de temps avant la crise. Deux patients avaient une atteinte digestive : un reflux gastro-œsophagien et une pseudo-obstruction intestinale chronique. La crise rénale était survenue entre 6 et 12 mois suivant les premiers signes de la sclérodermie hors Raynaud. La crise s'était déclarée en hiver, pour 2 patients, en été pour 3 patients et en automne pour le dernier. La pression artérielle systolique était comprise entre 150 et 200 mmHg. La créatininémie, au moment de la crise, était comprise entre 114 et 554 micromol/L. Quatre patients avaient une protéinurie supérieure à 1,5 grammes/grammes de créatininurie. Quatre présentaient des signes de microangiopathie thrombotique, 1 des signes d'encéphalopathie, 1 une hémorragie intra-alvéolaire et 3 une rétinopathie hypertensive stade II ou III. Deux patients avaient bénéficié d'une biopsie rénale montrant pour l'un une néphroangiosclérose et l'autre une glomérulonéphrite ischémique. Le traitement par inhibiteurs de l'enzyme de conversion (IEC) était débuté chez tous les patients et pour 4 patients, un traitement par inhibiteurs calciques. Quatre patients nécessitaient une épuration extrarénale, 3 à la phase aiguë de la crise rénale et un, 11 mois après. Parmi ces 4 patients, 1 décédait d'un choc septique à la phase aiguë de la crise, 2 nécessitaient une hémodialyse chronique et 1 était transplantée 22 mois après le début de la crise. Dans les cohortes les plus importantes de la littérature, la crise rénale apparaît après une médiane d'évolution de 7,5 mois [1,2]. Elle était de 8 mois dans notre série. L'utilisation de corticoïdes à forte dose, comme facteurs de risque de crise rénale, est controversée [2] et n'est pas soulignée dans notre série ; le rôle protecteur des IEC est lui aussi controversé et dans notre série, une seule patiente prenait ce traitement avant la crise rénale et ce dernier avait été arrêté récemment. La prédominance des anticorps anti-ARN-polymérase III n'était pas retrouvée dans notre série. Un cas d'hémorragie intra-alvéolaire, rarement décrit dans la littérature, a été retrouvé dans notre série. Cette présentation de 6 cas de crise rénale sclérodermique permet de rappeler que la crise rénale survient, le plus souvent, dans la première année après les premiers signes cliniques de la maladie et impose une vigilance accrue avec auto-mesures tensionnelles et surveillance de la créatininémie. Dans notre expérience, elle concerne aussi bien les sclérodermies systémiques limitées que diffuses. L'hypertension artérielle, au moment de la crise rénale, est le plus souvent modérée. Bien que difficile à mettre en évidence dans notre série, la prise en charge la plus précoce possible avec introduction d'IEC constitue probablement un facteur pronostique majeur permettant d'éviter la mise en dialyse chronique ou la transplantation [3]. [ABSTRACT FROM AUTHOR]

We conducted a national in-depth analysis including pharmacovigilance reports and clinical study to assess the reporting rate (RR) and to determine the clinical profile of polymyalgia rheumatica (PMR) and giant cell arteritis (GCA) in COVID-19-vaccinated individuals. First, based on the French pharmacovigilance database, we estimated the RR of PMR and GCA cases in individuals aged over 50 who developed their initial symptoms within one month of receiving the BNT162b2 mRNA, mRNA-1273, ChAdOx1 nCoV-19, and Ad26.COV2.S vaccines. We then conducted a nationwide survey to gather clinical profiles, therapeutic management, and follow-up data from individuals registered in the pharmacovigilance study. A total of 70 854 684 COVID-19 vaccine doses were administered to 25 260 485 adults, among which, 179 cases of PMR (RR 7. 1 cases/1 000 000 persons) and 54 cases of GCA (RR 2. 1 cases/1 000 000 persons) have been reported. The nationwide survey allowed the characterization of 60 PMR and 35 GCA cases. Median time to the onset of first symptoms was 10 (range 2-30) and 7 (range 2-25) days for PMR and GCA, respectively. Phenotype, GCA-related ischemic complications and -large vessel vasculitis as well as therapeutic management and follow-up seemed similar according to the number of vaccine shots received and when compared to the literature data of unvaccinated population. Although rare, the short time between immunization and the onset of first symptoms of PMR and GCA suggests a temporal association. Physician should be aware of this potential vaccine-related phenomenon.

Hypothesis: Amino acid-based surfactants have been proposed as skin permeation enhancers. In this work, we investigated the potentiality of two arginine-based amphiphiles as permeation enhancers by studying their interaction with stratum corneum (SC) model lipid membranes., Experiments: N α -benzoyl arginine decyl- and dodecylamide were tested in comparison with the classical enhancer, oleic acid, and the non-enhancer, stearic acid. Two complementary approaches were used: lipid monolayers, taken as models of the unit film layer of SC, and atomistic molecular dynamics simulations., Findings: The arginine-based amphiphiles studied were able to be incorporated into the SCM membrane and alter its rheological and structural properties by disordering the lipid chains, enhancing membrane elasticity, and thinning the overall membrane. They also affected the lateral structure of heterogeneous SC membranes at the nanoscale by relaxing and rounding the domain borders. Our work shows that the alteration observed of the overall rheological and structural properties of the SC membranes appears to be a shared ability for several amphiphilic permeation enhancers. Our results encourage future exploration of those amphiphiles as skin permeation enhancers., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objectives: To describe the effectiveness and safety of biologics for the treatment of relapsing and/or refractory polyarteritis nodosa (PAN)., Methods: A retrospective European collaborative study was conducted in patients with PAN who received biologics for relapsing and/or refractory disease., Results: Forty-two patients with PAN received a total of 53 biologic courses, including TNF-α blockers in 15 cases, rituximab (RTX) in 18 cases, tocilizumab (TCZ) in 10 cases and other biologics in 10 cases. TNF-α blockers and TCZ were mainly used for refractory diseases whereas RTX was mainly initiated for relapsing disease. After a median follow-up of 29 (8-50) months, remission, partial response, treatment failure and treatment discontinuation due to severe adverse events occurred in, respectively, 40%, 13%, 40% and 7% of patients receiving TNF-α blockers, 50%, none, 30% and 20% of TCZ recipients, and 33%, 11%, 56% and none of the RTX recipients. No remission was noted in patients treated with other biologics. Severe adverse events were observed in 14 (28%) patients without significant differences between the three biologics, leading to early biologics discontinuation in only three cases., Conclusion: These results suggest that TCZ may be effective in relapsing and/or refractory PAN. Our data warrant further study to confirm these findings., (© The Author(s) 2022. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Cationic amino acid-based surfactants are known to interact with the lipid bilayer of microorganism resulting in cell death through a disruption of the membrane topology. To elucidate the interaction of a cationic surfactant synthesized in our lab, investigations involving N α -benzoyl-arginine decyl amide (Bz-Arg-NHC 10 ), and model membranes composed by 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) were done. Bz-Arg-NHC 10 was able to penetrate into DPPC monolayers up to a critical pressure of 59.6 mN m -1 . Differential scanning calorimetry revealed that as the concentration of Bz-Arg-NHC 10 increased, the main transition temperature of DPPC slightly decreased. Atomic force microscopy (AFM) in situ experiments performed on supported DPPC bilayers on mica allowed monitoring the changes induced by Bz-Arg-NHC 10 . DPPC bilayer patches were partially removed, mainly in borders and bilayer defects for 50 µM Bz-Arg-NHC 10 solution. Increasing the concentration to 100 µM resulted in a complete depletion of the supported bilayers. Surface plasmon resonance (SPR) experiments, carried out with fully DPPC bilayers covered chips, showed a net increase of the SPR signal, which can be explained by Bz-Arg-NHC 10 adsorption. When patchy DPPC bilayers were formed on the substrate, a SPR signal net decrease was obtained, which is consistent with the phospholipids' removal observed in the AFM images. The results obtained suggest that the presence of the benzoyl group attached to the polar head of our compound would be the responsible of the increased antimicrobial activity against gram-negative bacteria when compared with other arginine-based surfactants.

The strong UV absorption of the bromide in aqueous solution undergoes a remarkable red shift of more than 10 nm induced by the addition of the salts that constitute a saline buffer. The maximum absorption wavelength of the bromide is displaced from approximately 194 nm in ultrapure water to wavelengths above 200 nm, depending on the composition of the solution. The bromide spectrum as counterion of the cetyltrimethylammonium in the surfactant CTAB also shows sensitivity to the aggregation behavior of the tensioactive, being able to detect intermolecular interactions even at concentrations lower than the critical micelle concentration. And, when the micelles are assembled, the bromide absorption detects the interfacial rearrangements caused by the incorporation of ions. To know more about those interfacial features, the pyrene molecular probe was used, taking advantage of the extensive knowledge of its spectroscopy. Pyrene verifies the existence of changes in the interfacial organization which confirm that the sensitivity of the bromide spectrum is based on the ability of the ion to detect its microenvironment, and therefore reaffirms that its absorption spectrum can be used as a local sensor. The present work encourages the use of bromide as a sensor ion in the UV region between 190 and 210 nm, which would avoid the introduction of external molecular probes that could disturb the system., (Copyright © 2019 Elsevier B.V. All rights reserved.)

A novel arginine-based cationic surfactant N α -benzoyl-arginine dodecylamide (Bz-Arg-NHC 12 ) was synthesized in our laboratory. In this paper we study the interaction of Bz-Arg-NHC 12 with sheep and human red blood cells (SRBC and HRBC respectively) due to their different membrane physicochemical/biophysical properties. SRBC demonstrated to be slightly more resistant than HRBC to the hemolytic effect of the surfactant, being the micellar structure responsible for the hemolytic effect in both cases. Moreover, besides the hemolytic effect, a dual behavior was observed for the surfactant studied: Bz-Arg-NHC 12 was also able to protect red blood cells against hypotonic lysis for HRBC in a wide range of surfactant concentrations. However, the degree of protection showed for SRBC was about 50% lower than for HBRC. In this regard, a remarkable volume expansion was evidenced only for SRBC treated with Bz-Arg-NHC 12 , although no correlation with the antihemolytic potency (pAH) was found. On the contrary, our surfactant showed a greater pAH when human erythrocytes were submitted to hypotonic stress, with a low volume expansion, showing a higher amount of solubilized phospholipids in the supernatant when compared with SRBC behavior. Surface plasmon resonance measurements show the molecular interaction of the surfactant with lipid bilayers from HRBC and SRBC lipids, demonstrating that in the latter neither microvesicle release or lipid extraction occurred. Our results demonstrate that the volume expansion of erythrocytes is not the only mechanism responsible for the protection by surfactants against hypotonic hemolysis: volume expansion could be compensated via microvesicle release or by the extraction of membrane components upon collisions between red blood cells and surfactant aggregates depending on the membrane composition., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Statin therapy decreases cardiovascular morbidity and mortality rates when used as either primary or secondary prevention. An immunomodulating effect of statins has been suggested. Incontrovertible evidence of accelerated atheroma has been obtained in patients with systemic lupus erythematosus (SLE). Routine statin therapy in SLE patients might therefore produce both cardiovascular and immunological benefits. However, routine statin therapy is inappropriate in SLE patients, the main reason being the absence of a vast interventional study done specifically in this population. An immunomodulating role for statins in SLE has not been convincingly established. The effect of statin therapy on markers for subclinical atheroma (intima-media thickness changes over time) is unclear, and there are no studies proving that statins are effective when used for primary or secondary cardiovascular prevention. Nevertheless, we believe that a serum lipid profile should be obtained once a year in all SLE patients. There is a sound rationale for classifying all SLE patients as being at high cardiovascular risk and those receiving secondary prevention as at very high risk. Consequently, the serum LDL-cholesterol level must be kept below 100 mg/dL and 70 mg/dL in these two populations, respectively. Statins are the only widely recommended drugs for achieving these treatment targets. Statin therapy requires specific monitoring precautions (transaminase levels) given the high prevalence of comorbidities and use of concomitant medications in SLE patients., (Copyright © 2012 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.)