Influence of the normal load of scratching on cracking and mechanical strength of soda-lime-silica glass

International audienceThe response of glass to a scratch experiment is first reviewed. Then the influence of the applied load on the microcracking pattern, the apparent friction coefficient, and the strength (post scratch test) are studied and discussed for a soda-lime-silica glass (standard window glass composition). As the normal load increases, the depth of the radial crack seems to stabilize at about 100 μm length. Correlatively it is observed that the residual strength of the scratched glass remains at about 40 MPa whatever the scratch load above 0.5 N. Generally, this work contributes theoretically in the understanding of the existing factor controlling scratch in glasses

Histaminergic angioedema and chronic urticaria

International audienceMost angioedemas are histaminergic and correspond to deep urticarial swelling. Recurrent histaminergic angioedema led to the diagnosis of chronic urticaria, even when there are no superficial associated hives. Chronic urticaria is a benign disease, and autoimmune in 40 % of cases. The occurrence of angioedema in chronic urticaria is not a sign of severity. The occurrence of angioedema in chronic urticaria is associated with a longer duration of urticarial disease. NSAIDs and/or systemic corticotherapy are classic triggers of angioedema in chronic urticaria. In the absence of clinical endpoints, there is no need to make further assessment in chronic urticaria good responders to antihistamines

Management and treatment outcome of DRESS patients in Europe : An international multicentre retrospective study of 141 cases

BackgroundDrug reaction with eosinophilia and systemic symptoms (DRESS) is a rare but potentially fatal drug hypersensitivity reaction. ObjectiveTo explore treatment approaches across Europe and their impact on the disease course, as well as prognostic factors and culprit drugs. MethodsIn this retrospective European multicentric study, we included patients with probable or certain DRESS (RegiSCAR score >= 4) between January 2016 and December 2020. Independent associations between clinical parameters and the risk of intensive care unit admission and mortality at three months were assessed using a multivariable-adjusted logistic regression model. ResultsA total of 141 patients from 8 tertiary centres were included. Morbilliform exanthem was the most frequent cutaneous manifestation (78.0%). The mean affected body surface area (BSA) was 67%, 42% of the patients presented with erythroderma, and 24.8% had mucosal involvement. Based on systemic involvement, 31.9% of the patients had a severe DRESS. Anticonvulsants (24.1%) and sulphonamides (22.0%) were the most frequent causative agents. In all, 73% of the patients were treated with systemic glucocorticoids, and 25.5% received topical corticosteroids as monotherapy. Few patients received antiviral drugs or anti-IL5. No patients received intravenous immunoglobulins. The overall mortality was 7.1%. Independent predictors of mortality were older age (>= 57.0 years; fully adjusted OR, 9.80; 95% CI, 1.20-79.93; p = 0.033), kidney involvement (fully adjusted OR, 4.70; 95% CI, 1.00-24.12; p = 0.049), and admission in intensive care unit (fully adjusted OR, 8.12; 95% CI, 1.90-34.67; p = 0.005). Relapse of DRESS and delayed autoimmune sequelae occurred in 8.5% and 12.1% of patients, respectively. ConclusionsThis study underlines the need for diagnostic and prognostic scores/markers as well as for prospective clinical trials of drugs with the potential to reduce mortality and complications of DRESS.Peer reviewe

Drug reactions with eosinophilia and systemic symptoms induced by immune checkpoint inhibitors: an international cohort of 13 cases

Among dermatologic adverse events induced by immune checkpoint inhibitors (ICI), drug reactions with eosinophilia and systemic symptoms (DRESS) have been very rarely reported. The objective of this study is to better define the clinical and histologic features, treatment and prognosis of ICI-related DRESS. This retrospective case series was conducted between 01 January 2015 and 31 December 2021 by the dermatology departments of five international networks involved in drug reactions. Inclusion criteria were age ≥18 years old, DRESS with Regiscar score ≥4 (probable or certain) and ICI as a suspect drug. Clinical, biologic and follow-up data were extracted from the medical charts. Thirteen patients were included. The median time to onset was 22 days (3-11). No patients had a high-risk drug introduced in the past 3 months. A majority of patients presented fever (92%), diffuse exanthema (77%) and facial edema (69%). Biologic features included hypereosinophilia in eight patients (61.5%), hyperlymphocytosis in 3 (23%), elevated liver function tests in 11 (85%, grade 1 or 2 in most cases) and renal involvement in 5 (38%). Two patients (15%) had lung involvement. PCR evidence of viral replication was detected in five patients (38.5%). Treatment involved discontinuation of the suspect ICI and systemic steroids with variable dose and duration regimens. Among the four patients in which ipilimumab + nivolumab combination therapy was initially suspected, one was rechallenged with nivolumab monotherapy with good tolerance. Five patients were switched to another anti-PD-1 plus low-dose systemic steroids, with good tolerance in four cases. No patient died because of DRESS. DRESS induced by ICI are rare and of moderate severity. A consensus for management is still pending

Epidermal necrolysis French national diagnosis and care protocol (PNDS; protocole national de diagnostic et de soins).

International audienceEpidermal necrolysis (EN) encompasses Stevens-Johnson syndrome (SJS, < 10% of the skin affected), Lyell syndrome (toxic epidermal necrolysis, TEN, with ≥30% of the skin affected) and an overlap syndrome (10 to 29% of the skin affected). These rare diseases are caused, in 85% of cases, by pharmacological treatments, with symptoms occurring 4 to 28 days after treatment initiation. Mortality is 20 to 25% during the acute phase, and almost all patients display disabling sequelae (mostly ocular impairment and psychological distress).The objective of this French national diagnosis and care protocol (protocole national de diagnostic et de soins; PNDS), based on a critical literature review and on a multidisciplinary expert consensus, is to provide health professionals with an explanation of the optimal management and care of patients with EN. This PNDS, written by the French National Reference Center for Toxic Bullous Dermatoses was updated in 2017 ( https://www.has-sante.fr/portail/jcms/c_1012735/fr/necrolyse-epidermique-syndromes-de-stevens-johnson-et-de-lyell ). The cornerstone of the management of these patients during the acute phase is an immediate withdrawal of the responsible drug, patient management in a dermatology department, intensive care or burn units used to dealing with this disease, supportive care and close monitoring, the prevention and treatment of infections, and a multidisciplinary approach to sequelae. Based on published data, it is not currently possible to recommend any specific immunomodulatory treatment. Only the culprit drug and chemically similar molecules must be lifelong contraindicated

The protein status of rats affects the rewarding value of meals due to their protein content

[Background] Protein status is controlled by the brain, which modulates feeding behavior to prevent protein deficiency. [Objective] This study tested in rats whether protein status modulates feeding behavior through brain reward pathways. [Methods] Experiments were conducted in male Wistar rats (mean ± SD weight; 230 ± 16 g). In experiment 1, rats adapted for 2 wk to a low-protein (LP; 6% of energy) or a normal-protein (NP; 14% of energy) diet were offered a choice between 3 cups containing high-protein (HP; 50% of energy), NP, or LP feed; their intake was measured for 24 h. In 2 other experiments, the rats were adapted for 2 wk to NP and either HP or LP diets and received, after overnight feed deprivation, a calibrated HP, NP, or LP meal daily. After the meal, on the last day, rats were killed and body composition and blood protein, triglycerides, gut neuropeptides, and hormones were determined. In the brain, neuropeptide mRNAs in the hypothalamus and c-Fos protein and opioid and dopaminergic receptor mRNAs in the nucleus accumbens (NAcc) were measured. Results Rats fed an LP compared with an NP diet had 7% lower body weight, significantly higher protein intake in a choice experiment (mean ± SD: 30.5% ± 0.05% compared with 20.5% ± 0.05% of energy), higher feed-deprived blood ghrelin, lower postmeal blood leptin, and higher neuropeptide Y (Npy) and corticotropin-releasing hormone (Crh) mRNA expression in the hypothalamus. In contrast to NP, rats fed an LP diet showed postmeal c-Fos protein expression in the NAcc, which was significantly different between meals, with LP < NP < HP. In contrast, in rats adapted to an HP diet compared with an NP diet, energy intake was lower; and in the NAcc, meal-induced c-Fos protein expression was 20% lower, and mRNA expression was 17% higher for dopamine receptor 2 (Drd2) receptors and 38% lower for κ opioid receptor (Oprk1) receptors. [Conclusion] A protein-restricted diet induced a reward system–driven appetite for protein, whereas a protein-rich diet reduced the meal-induced activation of reward pathways and lowered energy intake in male rats.Supported by public funding from AgroParisTech (Paris, France) and Institut National de la Recherche Agronomique (INRA, France).Peer reviewe

Severe blistering eruptions induced by immune checkpoint inhibitors: a multicentre international study of 32 cases.

Among dermatologic adverse events induced by immune checkpoint inhibitors (ICI), bullous life-threatening reactions are rare. To better define the clinical and histological features, treatment, and prognosis of ICI-related severe blistering cutaneous eruptions. This retrospective case series was conducted between 2014/05/15 and 2021/04/15 by the dermatology departments of four international registries involved in drug reactions. Inclusion criteria were age ≥18 years old, skin eruption with blisters with detachment covering ≥1% body surface area and at least one mucous membrane involved, available pictures, and ICI as suspect drug. Autoimmune bullous disorders were excluded. Each participant medical team gave his own diagnosis conclusion: epidermal necrolysis (EN), severe lichenoid dermatosis (LD), or unclassified dermatosis (UD). After a standardized review of pictures, cases were reclassified by four experts in EN or LD/UD. Skin biopsies were blindly reviewed. Thirty-two patients were included. Median time to onset was 52 days (3-420 days). Cases were originally diagnosed as EN in 21 cases and LD/UD in 11 cases. After review by experts, 10/21 EN were reclassified as LD/UD. The following manifestations were more frequent or severe in EN: fever, purpuric macules, blisters, ocular involvement, and maximal detachment. Most patients were treated with topical with or without systemic corticosteroids. Eight patients (25%) died in the acute phase. The culprit ICI was not resumed in 92% of cases. In three patients, another ICI was given with a good tolerance. Histology did not reveal significant differences between groups. Severe blistering cutaneous drug reactions induced by ICI are often overdiagnosed as EN. Consensus for management is pending

AM 251 produces sustained reductions in food intake and body weight that are resistant to tolerance and conditioned taste aversion

1. The cannabinoid 1 (CB(1)) receptor has been implicated in the regulation of food intake. Here, we examine the effect of the CB(1) receptor antagonist AM 251 on food intake and body weight over a prolonged period. Further, we examine whether AM 251 produces conditioned taste aversion (CTA) and if sustained antagonism at central receptors contributes to its anorectic effect. 2. The effect of AM 251 of food intake and body weight was examined in daily (1 mg kg(−1)) and 5-day (5 mg kg(−1)) dosing schedules. Matching reductions in food intake and body weight were observed in both paradigms. A single administration of AM 251 (5 mg kg(−1)) significantly reduced food intake for 4 days. Tolerance to the anorectic effects of AM 251 did not develop in either dosing strategy. 3. Active avoidance of AM 251 (3; 5 mg kg(−1), i.p.) was examined using a CTA assay. Rats showed no evidence of CTA associated with AM 251. 4. We investigated the sustained effect of AM 251 (5 mg kg(−1), i.p.) on CB(1) receptors in the hypothalamus using Δ(9)-tetrahydrocannabinol (8 mg kg(−1), i.p.) induced hypothermia. AM 251 initially blocked hypothermia, but this effect was not seen 2 or 4 days later. 5. The results demonstrate that smaller, or infrequent, administrations of AM 251 can produce sustained reductions in food intake and body weight in rat. Reductions in food intake were sustained longer than AM 251 antagonized the effects of a CB(1) receptor agonist in the hypothalamus, and occurred independently of CTA