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Background: Toxic epidermal necrolysis is a rare and life-threatening mucocutaneous disease. Although mucosal ear, nose, and throat (ENT) involvement is common, little is known about the characteristics, treatment modalities, and outcomes of these lesions. The aim of this study was to evaluate ENT mucosal lesions in severe toxic epidermal necrolysis patients and analyze their characteristics, treatment modalities, and outcomes, as well as proposing a management algorithm to prevent long-term debilitating sequalae of these lesions., Methods: This is a retrospective review of toxic epidermal necrolysis cases treated at the tertiary burns unit of the Lausanne University Hospital CHUV, Switzerland, between 2006 and 2019., Results: Out of 19 patients with severe toxic epidermal necrolysis, 17 (89%) underwent a complete ENT examination at admission and 14 (82%) had ENT mucosal involvement. Five (26.3%) patients died during the stay in the intensive care unit. Of the 16 patients who received maximal care, 13 (81%) required orotracheal intubation for a median time of 16 (IQR: 14) days. Out of the 14 patients who survived, four (29%) had long-term ENT complications consisting of synechiaes necessitating subsequent endoscopic procedures. Those four patients all required mechanical ventilation with an orotracheal tube and suffered from hypopharyngeal synechiaes as well as oral and endonasal synechiaes in individual cases., Conclusion: This study suggests a high prevalence of ENT synechiaes in patients with severe toxic epidermal necrolysis and requiring orotracheal intubation. Periodic ENT examination could prevent mature synechiae formation in these patients. We propose an algorithm to prevent long-term sequalae in ENT mucosal involvement., (© 2023 The Authors. International Journal of Dermatology published by Wiley Periodicals LLC on behalf of the International Society of Dermatology.)

Acute tonsillitis is a common disease. The tonsillar infection can be uni- or bilateral with a high rate of spontaneous recovery. In some cases, a peritonsillar cellulitis or abscess can occur, characterized by an inflammatory reaction of the peritonsillar space. The red flags consist of a gradually worsening odynodysphagia, an ipsilateral swelling of the soft palate, a trismus (infrequent in children) and in some cases a change of voice (« hot potato voice »). A needle puncture of the swollen soft palate is then required. If pus is found, a surgical drainage by either hot tonsillectomy or incision under local anesthesia with an appropriate antibiotic therapy must be carried out., Competing Interests: Les auteurs n’ont déclaré aucun conflit d’intérêts en relation avec cet article.

Introduction  All patients with a new head and neck squamous cell carcinoma (HNSCC) undergo diagnostic panendoscopy as part of the screening for synchronous second primary tumors. It includes a pharyngolaryngoscopy (PLS), a tracheobronchoscopy and esophagoscopy, and a stomatoscopy. Rigid techniques are risky, with long learning curves. Objective  We propose a precise description of the panendoscopy protocol. We include an optimization of the PLS technique that completes the flexible esophagoscopy when rigid esophagoscopy isn't performed. Methods  The present retrospective observational study includes 122 consecutive patients with a new primary HNSCC who underwent traditional panendoscopy and the new PLS technique between January 2014 and December 2016. A two-step procedure using a Macintosh laryngoscope and a 30° telescope first exposes panoramically the larynx, the upper trachea, and the oropharynx; then, in a second step, the hypopharynx is exposed down to the upper esophageal sphincter. Broncho-esophagoscopy is performed with a rigid and flexible scope. Results  In total, 6 (5%) patients presented synchronous tumors (3 in the esophagus, 2 in the oral cavity, and 1 in the larynx 1). Rigid endoscopy was complicated by 2 (1,6%) dental lesions, and had to be completed with a flexible scope in 38 (33%) cases for exposition reasons. The two-step PLS offered a wide-angle view of the larynx, upper trachea, and oro- and hypopharynx down to the sphincter of the upper esophagus. The procedure was easy, reliable, safe, repeatable, and effectively completed the flexible endoscopies. Conclusion  Rigid esophagoscopy remains a difficult procedure. Two-step PLS combined with flexible broncho-esophagoscopy offers good optical control., Competing Interests: Conflict of Interests The authors have no conflict of interests to declare., (Fundação Otorrinolaringologia. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commecial purposes, or adapted, remixed, transformed or built upon. ( https://creativecommons.org/licenses/by-nc-nd/4.0/ ).)

Objective: Supraglottic stenosis (SPGS) is a rare condition and little is known about its optimal management. Its etiologies are varied and depend on the age group. Here, we review our institution's series of patients and propose treatment strategies for SPGS., Methods: SPGS patients between 2013 and 2019 were retrospectively reviewed. We recorded their demography, clinical data and endoscopy. The patients were treated with either an endoscopic, open or a combined approach. Subsequently, we reviewed photo and video documents, medical sheets and long-term follow-up charts., Results: The report includes 14 children having a mean age of 5.7 years (range 2 months-13 years). Seven children had undergone prior supraglottoplasty for laryngomalacia, three children had blunt neck trauma and four had iatrogenic plus post-intubation etiology. Five children received endoscopic treatment and are currently symptom free. Four patients received a combined repair with satisfactory results. Five children received an open repair, four of which are decannulated and feed orally without aspiration. Most children in this group required additional endoscopic interventions., Conclusion: Post supraglottoplasty stenosis can be treated optimally by an endoscopic approach. More severe supraglottic cicatrical sequelae with posterior glottic involvement may require a combined endoscopic and open approach. Transglottic stenoses with severe grades of multi-level stenoses require an extended cricotracheal resection.

Cobalt is known to be toxic at high concentration, to induce contact dermatosis, and occupational radiation skin damage because of its use in nuclear industry. We investigated the intracellular distribution of cobalt in HaCaT human keratinocytes as a model of skin cells, and its interaction with endogenous trace elements. Direct micro-chemical imaging based on ion beam techniques was applied to determine the quantitative distribution of cobalt in HaCaT cells. In addition, synchrotron radiation X-ray fluorescence microanalysis in tomography mode was performed, for the first time on a single cell, to determine the 3D intracellular distribution of cobalt. Results obtained with these micro-chemical techniques were compared to a more classical method based on cellular fractionation followed by inductively coupled plasma atomic emission spectrometry (ICP-AES) measurements. Cobalt was found to accumulate in the cell nucleus and in perinuclear structures indicating the possible direct interaction with genomic DNA, and nuclear proteins. The perinuclear accumulation in the cytosol suggests that cobalt could be stored in the endoplasmic reticulum or the Golgi apparatus. The multi-elemental analysis revealed that cobalt exposure significantly decreased magnesium and zinc content, with a likely competition of cobalt for magnesium and zinc binding sites in proteins. Overall, these data suggest a multiform toxicity of cobalt related to interactions with genomic DNA and nuclear proteins, and to the alteration of zinc and magnesium homeostasis.

Background: This study investigates the relationship between the burn-induced oxidative stress and the selenium status., Methods: The rats were fed with a selenium-adequate diet or a selenium-depleted diet for 5 weeks, before a third-degree thermal injury was applied to the animals. One group of selenium-depleted animals received injections of sodium selenite after the injury. The selenium status and the oxidative stress parameters were measured for 5 days., Results: The selenium-deficient diet leads to oxidative stress with a high stimulation of the superoxide dismutase activity. After the burn injury, the oxidative stress appears important because the initial selenium status is already impaired and, in all animals, the selenium levels and the antioxidant seleno-dependent glutathione peroxidase (GPx) activity decrease in the plasma and the tissues. A treatment with daily selenium injections is efficient in normalizing selenium levels and restores the GPx activity, but fails to counteract the initial oxidative damages induced by the selenium-deficient diet., Conclusions: The selenium status before the burn injury is a modulating factor of the burn-induced oxidative stress. A single selenium supplement is not sufficient to counteract these oxidative damages and henceforth combined antioxidant supplementations should be investigated to improve the early treatment of the burn patients.

Our objective was to demonstrate a role of chromium (Cr) in response to severe burn. A third-degree burn involving 20% of total body surface was applied under anaesthesia in accord with ethical guidelines. Chromium concentrations in liver decreased progressively and were non-detectable on days 5 and 10 following injury. In quadriceps muscle, Cr concentrations increased 6h after injury and then declined significantly within the first day and remained at these levels the following 9 days. Urinary Cr losses were also increased. Changes in kidney, brain and serum Cr were not significant. Non-fasting glucose rose 6h after injury and then returned to levels measured before the burn. There was a significant rise in corticosterone reaching a maximum the first day after injury that was accompanied by significant increases in circulating insulin and glucagon that were maximal after 2 days. Changes in IGF-1 were not significant. In summary, changes in Cr concentrations were associated with an early hyperglycemia, hyperinsulinemia and increased secretion of stress hormones. These observations strongly suggest a mobilization and utilization of Cr following severe burn. Additional studies are needed to document that improved Cr status might lead to improved recovery following burn.

In order to investigate the efficiency of a single selenium (Se) administration in restoring selenium status, Se and antioxidant enzymes were studied in an animal model of Se depletion. In Se-depleted animals receiving or not a single parenteral administration of Se, plasma, red blood cell (RBC), and tissue Se levels were measured concurrently with glutathione peroxidase (GPx) and superoxide dismutase (SOD) activities. The oxidative stress was assessed by thiobarbituric acid-reactive species (TBARs), total thiol groups, glutathione, and tocopherol measurements. Our study showed that Se depletion with alterations in the antioxidant defense system (Se and GPx activity decreases) led to an increase of lipid peroxidation, a decrease of the plasma vitamin E level, and SOD activation. Sodium selenite injection resulted after 24 h in an optimal plasma Se level and a reactivation of GPx activity. In liver, brain, and kidney, Se levels in injected animals were higher than those in reference animals. However, this single administration of Se failed to decrease free radical damage induced by Se depletion. Therefore, in burned patients who exhibit an altered Se status despite a daily usually restricted Se supplementation, the early administration of a consistent Se amount to improve the GPx activity should be of great interest in preventing the impairment of the antioxidant status.

The objective of the present study was to measure the relationship between selenium status and oxidative stress in two rat models of thermal injury. A non-lethal third-degree burn injury involving 20% (experiment 1) or 40% (experiment 2) of total body surface area (TBSA) was applied to male Wistar rats. Selenium level, glutathione peroxidase (GPx) activity in plasma, red blood cells (RBC) and tissues (liver, kidney, muscle, and brain), and plasma selenoalbumin (Se-alb) were measured in control rats and in burned rats respectively 6 hours after injury and daily from day 1 to day 5. In parallel, lipid and protein oxidative damages, monitored by plasma and tissue thiobarbituric acid reactive species (TBARs) levels and plasma total thiol groups were assessed. We observed a decrease of plasma Se and Se-albumin 6 hours after burn injury. In parallel, plasma GPx activity rapidly decreased and remained significantly lower than in control rats. These alterations were enhanced by the burn injury severity. Plasma TBARs followed the same pattern as that of plasma cholesterol, with an initial decrease and an increase at day 3 in 40% TBSA burned rats. Plasma thiol groups decreased in the two experiments indicating plasma protein oxidation. These results confirm an early oxidative stress in burn injury, and suggest an early selenium mobilization, which might counteract this oxidative stress. These data underline the crucial need of a restored selenium status in burned patients immediately after the burn injury.

Besides its role as a barrier against potential pathogens, intestinal flora is presumed to protect the host by priming the immunological defense mechanisms. In this respect, the influence of intestinal flora on macrophage precursors was examined, and its modulating effect was compared on LPS-induced cytokine production by macrophages derived from bone marrow and spleen precursors (BMDM and SDM respectively). The regulation of IL-1, IL-6, TNF-alpha and IL-12 production in macrophages from germ-free and from three groups of flora-associated mice, conventional, conventionalized and E. coli-mono-associated mice, was investigated. The whole flora inhibited IL-1, TNF-alpha and IL-12 secretion by BMDM, whereas it had a stimulatory effect on IL-12 secretion by SDM. Implantation of E. coli alone enhanced cytokine secretion by BMDM but had a more limited effect than whole flora on SDM, enhancing only TNF-alpha and IL-12 secretion. Study of expression of mRNA showed a correlation with protein secretion for IL-6 but not for TNF-alpha and IL-1. IL-12 enhancement in BMDM seemed to be dependent on regulation of p35 mRNA expression while it was correlated to increased p40 mRNA expression in SDM. The results demonstrated that intestinal flora modulated bone marrow and spleen macrophage cytokine production in a differential manner and suggested a role for bacteria other than E. coli among the whole flora. The contrasting effects exerted by the intestinal flora on bone marrow and spleen precursors are an interesting observation in view of the different functions of these organs in immunity. The finding that intestinal flora enhanced IL-12 production in spleen is also potentially important since this cytokine is implicated in the determination of the relative levels of Th1 and Th2 responses and plays a pivotal role in host defense against intracellular microorganisms.

To assess the involvement of bacterial microflora in the development of host defenses, we compared in vitro LPS-induced cytokine production by macrophages in germ-free and E. coli monoxenic mice. E. coli implantation significantly increased IL-1 and IL-6 and, to a lesser extent, TNF activities of peritoneal and bone marrow-derived macrophages. These results suggest that exposure to microflora primes macrophages for an enhanced cytokine production, which may contribute to the activation of the antiinfectious defense. The priming was not restricted to peritoneal macrophages but was associated with a more general effect of the flora since the enhanced response of bone marrow-derived macrophages indicates an effect on macrophage precursors. Furthermore, a higher ability of peritoneal macrophages to produce IL-1 in axenic and monoxenic mice was observed as compared to bone marrow-derived macrophages. In contrast, bone marrow-derived macrophages demonstrated a higher ability to produce IL-6 and TNF but only 3 weeks after bacterial administration.

The specificity of various monoclonal antidigitoxin antibodies was characterized using 6 cardiac glycoside analogs. Spleen cells from BALB/c mice, immunized with BSA- or KLH-digitoxin conjugates, were fused with NS1 myeloma cells, and antibody-producing hybrids were identified by radioimmunoassay. Twenty-one monoclonal antidigitoxin-specific antibodies were obtained, 10 of which were cloned and characterized for affinity and specificity. All the antibodies had a high affinity constant, ranging from 8.10(8) to 2.5.10(10) 1/M. On the basis of their binding specificities, the antibodies could be classified into 3 groups: the first contained 7 antibodies exhibiting high cross reactivity (42-100%) with digitoxigenin, whereas the second and third groups did not recognize this analog (cross-reactivity of 1%). In the former group, the absence of the sugar moiety only slightly affected the binding reaction, although for the two other groups, this structure did appear to be involved in antibody recognition. Changes in the functional groups of the hapten molecule led to considerable changes in the antibody-antigen reaction. For all the antibodies except one, saturation of the lactone ring considerably affected binding. These results demonstrated that monoclonal antibodies of different specificities with respect to both the steroid backbone and the sugar moiety of digitoxin can be induced using a digitoxin-protein conjugate.