Toxic Epidermal Necrolysis

Belle.ai provides a differential diagnosis from more than 2,000 different skin conditions leveraging a database trained on over 500,000 images. The image referencing technology deploys deep learning to analyze an uploaded clinical image and then matches its geometric pattern characteristics to Belle.ai's database of images to provide reference differentials. The purpose is to determine the validity of the Belle.ai software in diagnosing common dermatologic diseases across a range of skin tones. Consented patients will have three images taken of their dermatologic disease within the Belle.ai software. These images will be uploaded and saved within the Belle system where a single AI-generated differential list will be generated based on the three photos. The study coordinator will review uploaded patient "cases" and assign the cases for review and adjudication to designated Dermatologic Review Committee (DRC) members within the Belle web portal. Successful validation will require \>80% concordance between Belle.ai's primary working diagnosis (#1 on the differential) and our dermatology experts. A team of dermatology experts will then secondarily assess the concordance among the remaining diagnoses.

The objectives of this study are to understand the variation in dermatoses presenting in individuals from different ancestry backgrounds. This will be conducted at multiple NHS hospitals in England. The Investigators specifically aim to 1) assess features of dermatoses in individuals of different ancestry. 2) Understand the language used by patients describing their condition.

The purpose of this research is to study a Chinese herbal Complementary and Alternative Medicine (CAM) product for the temporary relief of pain and itching after radiotherapy (RT). This is an over-the-counter product with 1% menthol as an active ingredient.

The level of involvement for each network institution will vary based on the type of specimen to which they have access (e.g. biofluids, tissues and/or cells) and the category of collection (remnant specimens that were originally collected for clinical testing and/or specimens specifically collected for research) in accordance with the institution's elected preferences. In most cases, potential participants will be identified and approached upon presenting for clinical care or recruited specifically for the study using outreach programs. If additional screening activities are required to determine eligibility criteria, the potential participant may be presented with the opportunity to participate in these activities as part of the study. These screening activities will be minimal risk in nature and are described further below. Should potential participants meet screening criteria, they may then be asked to provide biospecimens according to current research needs. Individual participants or groups of participants may be sought according to specific clinical, lifestyle, and/or demographic characteristics. The providers of these samples may be healthy participants or participants with a medical condition of interest to the research community but regardless, all specimens collected under this protocol (whether for screening purposes and for distribution to researchers) will qualify as minimal risk activities. Biospecimens may be distributed to researchers at academic institutions, hospitals, clinical and government laboratories, and corporations including diagnostic, medical device, biopharmaceutical and biotechnology companies. The types of research studies and testing that may be performed using the biospecimens will be varied, and it is not possible to provide a description of all potential studies. Some researchers may perform genetic testing on the specimens, some may use the specimens to develop cell lines, and some may cryopreserve the specimens for many years, awaiting a research use. The specimens may also be used for educational purposes, such as training lab techs on the proper testing of samples or physicians on the proper reading of stained slides. The iSpecimen consent forms will indicate a broad scope of possible research and educational uses and activities.

Pemphigus diseases are life-threatening chronic autoimmune blistering diseases characterized by split formation within the epidermis and surface-close epithelia accompanied by acantholysis. Autoantibodies (Abs) are mainly directed against two structural proteins of the epidermal/epithelial desmosome, desmoglein (Dsg) 1 and Dsg3. Two main pemphigus variants can be differentiated, pemphigus vulgaris (PV), and pemphigus foliaceus (PF). Diagnosis of PV and PF is based on the combination of the clinical picture, histological picture of acantholysis, direct immunofluorescence microscopy (DIF) of a perilesional biopsy and serology. The present "Ritux 4" trial is the fourth academic study with the French study group on auto immune bullous skin diseases (Groupe Bulle) to assess the use of rituximab in auto immune bullous skin diseases, in particular pemphigus. The 3 previous trials have been published in outstanding Journals (N Engl J Med 2007, Science Transl Med 2013, The Lancet 2017 and 2020), and have led to the approval of rituximab in pemphigus by the FDA in 2018 and EMA in 2019. In addition, an industry-sponsored trial testing rituximab versus mycophenolate mofetil in pemphigus, that the investigators have largely contributed to design has been very recently accepted for publication in the N Engl J Med (2021). The investigator hypothesize that a maintenance therapy using an infusion of 1g of rituximab at Month 6 in patients whose anti-Dsg Abs have not sufficiently decreased at Month 3 after the initial cycle of rituximab (persistence of anti-Dsg1 Abs\> 20 UI/ml and/or anti-Dsg3 Abs\> 130 UI/ml), and or had an initial PDAI score \>45 ( first year of follow-up), and the re-treatment with 1g of rituximab of patients whose anti Dsg Abs re-increase during the evolution of pemphigus after the initial cycle of rituximab (anti-Dsg1 Abs\> 20 IU/ml, anti-Dsg3 Abs\> 50 UI/ml), could be effective in preventing the occurrence of relapses, thus avoiding to restart a CS treatment, and would provide benefit as compared with the current treatment strategy of retreating patients with 2 g of rituximab (1g at Day0 and Day14) combined with oral CS patients, once a clinical relapse occurs.

Intro: Dermatology department of Henri Mondor Hospital (Creteil, France), is a reference center for toxic bullous diseases and severe cutaneous drug reactions (Stevens-Johnson syndrome (SJS), Lyell syndrome (toxic epidermal necrolysis (TEN)), generalized bullous fixed drug reactions, AGEP, DRESS, drug induced immunoglobulin A (IgA) bullous dermatosis, and erythema multiforme). In order to conduct clinical and biological research studies in drug reactions, it is necessary for the investigator's department to implement a collection of clinical data and biological samples. Hypothesis/Objective: To collect clinical data and cutaneous and biological samples for immunological, biological and genetic studies to improve knowledge about pathophysiology of drug reactions. Method: The following samples will be performed in addition to the routine practice samples: one skin punch biopsy (6mm); 43 mL of blood; blister fluid aspiration; oral and nose mucous membrane and skin eSWABs, stool samples. These samples will be stored in a dedicated biological sampling department ("Platform of biological resources"). Conclusion: The implementation of this collection should allow us to conduct pathophysiological studies about drug reactions.

The objective of this clinical trial is to evaluate the effectiveness and safety of transcutaneous posterior tibial nerve stimulation therapy in patients with premature ejaculation. The main question to answer is: Can the effectiveness and safety of transcutaneous electrostimulation of the posterior tibial nerve alone and combined with standard pharmacological treatment be evaluated in men with lifelong premature ejaculation, compared to standard pharmacological treatment with dapoxetine? Patients will: Be randomized in acontrolled clinical trial. Patients with a diagnosis of premature ejaculation who attend Boston Medical Group clinics in Mexico City will be included. Be assigned by randomization to one of three treatment groups: * Group 1: Tens therapy + dapoxetine placebo on demand. * Group 2: Standard treatment (dapoxetine 30 mg as needed) + placebo therapy. * Group 3: Tens therapy + standard treatment (dapoxetine 30 mg as needed).

Currently, surgery is a decisive therapeutic element in the management of women with breast cancer and at high risk for breast/ovarian cancer. In the first scenario, oncological surgery has evolved towards more complex technical procedures, such as oncoplastic surgery or skin-nipple-sparing mastectomies. These procedures have improved the quality of breast conservation or breast reconstruction, but have also increased the incidence of postoperative complications. In the second scenario, risk reduction mastectomies also share this same problem with an increase in adverse events after the use of ultra-conservative mastectomies. Without a doubt, skin necrosis is the most significant adverse event during the postoperative period in these patients due to three reasons. The first focuses on patients with breast cancer in whom skin necrosis delays the start of adjuvant treatments to surgery, chemotherapy or radiotherapy, causing greater complexity in their care process. Secondly, a significant number of these women with skin necrosis will require a second surgery to close the defect in the skin coverage, generally using a local flap, increasing care saturation and healthcare costs. Finally, these skin necrosis generate anatomical defects that in many cases will lead to cosmetic sequelae, worsening satisfaction and quality of life in this group of women. These consequences are especially relevant in women with prepectoral breast reconstruction, since the absence of muscle between the skin and the implant facilitates the exposure of the latter and, on occasions, the loss of the reconstruction. During the last 15 years our unit has published various articles analyzing adverse events during the postoperative period in patients with oncoplastic, reconstructive and risk reduction surgery. Thus, in a comparative study between lumpectomy and oncoplastic surgery in patients in our unit, an incidence of skin necrosis of 2.5% was demonstrated in oncoplastic procedures compared to 0.1% in lumpectomy. This higher incidence of complications had a significant impact on the delay for the start of radiotherapy, increasing this delay by 10 days compared to the group with lumpectomy. In the context of mastectomy, our unit has recently published the results of its prospective study PreQ 20 and it has shown an incidence of 5.6% of necrosis and skin dehiscence in women with skin-sparing mastectomy and breast cancer. Finally, another prospective study identified technical complexity and the appearance of postoperative complications as the two variables related to the appearance of cosmetic sequelae during follow-up in patients in our unit. These results highlight the value of prevention and/or early identification of skin ischemia to reduce the rate of necrosis during the postoperative period, guarantee delays during the care process, reduce cosmetic sequelae, and increase satisfaction and quality of life for women. with breast cancer and/or at high risk. Various studies have evaluated ICG angiography as a diagnostic method in mastectomy skin flap perfusion. To our knowledge, only two nonrandomized prospective studies have evaluated the sensitivity, specificity, and predictive values of this technique. The study by Phillips et al evaluated this procedure in 51 immediate reconstructions with expanders for the prediction of postoperative skin necrosis. Sensitivity, specificity, positive (PPV) and negative (NPV) predictive value were 90%, 50%, 56% and 88%, respectively. On the other hand, in the study by Munabi et al these values were 88%, 83%, 44% and 98%, respectively. In this latter study the authors found that smoking and epinephrine injection decreased the specificity of this diagnostic method from 98% to 83%. These studies have two limitations. The first refers to the fact that they have been performed in patients with a retropectoral breast reconstruction and through the use of expanders. Currently this type of reconstruction has been replaced by prepectoral reconstruction with direct implantation and for this reason we lack information on this new surgical modality. On the other hand, there are no studies that have evaluated ICG angiography in women with oncoplastic procedures. A Cochrane Library review was recently published whose objective was to evaluate the capacity of ICG angiography for the prevention of necrosis in mastectomy skin flaps in women undergoing immediate reconstruction after skin-sparing mastectomy. In this review we found nine studies that compared the number of postoperative complications in women undergoing ICG breast skin assessment versus clinical assessment. In these studies, a total of 1,589 women with 2,199 breast reconstructions were evaluated, and the number of complications per patient or per breast was reported. The main patient-related results of this review were that: * ICG can reduce reoperation rates. * there is uncertainty as to whether ICG decreases the rates of mammary skin necrosis, infection, hematoma and seroma. The main results referring to the breast were: * ICG can reduce mammary skin necrosis, reoperation rates and infection. * there is uncertainty as to whether ICG has an effect on hematoma and seroma rates. The evidence from the studies evaluated during this review is considered to be of very low quality as there are no prospective randomized studies. This review emphasizes the need for prospective studies to further investigate the use of the ICG in oncoplastic and reconstructive surgery of the breast. These uncertainties have encouraged us to carry out this prospective study in order to evaluate the role of indocyanine green angiography in the intraoperative identification of skin areas at risk for the appearance of necrosis in the skin cover of the breast in women operated on by an immediate oncoplastic or reconstructive procedure. Usually, when we talk about a diagnostic procedure such as ICG angiography, its sensitivity, specificity, positive predictive value, and negative predictive value are described. These parameters reflect the characteristics of the diagnostic test and serve to decide when they should be used (sensitivity and specificity of the test) or what is the meaning of this test in a particular patient. Unfortunately, the scientific literature has not evaluated these parameters for ICG angiography in the context of prepectoral reconstruction and oncoplastic surgery, which leads to empirical use of this procedure. The ultimate goal of this study is to provide information on the sensitivity, specificity, and predictive values of ICG angiography in these two clinical settings. With this, we intend to identify those patients in whom this diagnostic procedure provides added value in their surgical planning, reducing the incidence of skin necrosis and other associated surgical complications.

To evaluate the efficacy and safety of methylprednisolone combined with the JAK inhibitor abxitinib and tofacitinib in the treatment of toxic epidermal necrolysis

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare severe cutaneous adverse reactions (SCARs) to drugs. To date, no curative drug has demonstrated with a good level of evidence its ability to promote SJS and TEN healing and could contribute to earlier reepithelialisation. Mesenchymal stroma cells (MSCs) therapy represents a new therapeutic approach. eg, in patients with cardiovascular diseases, neurological diseases, renal transplantation, lung diseases as acute respiratory distress syndrome. Recently, MSCs have been proposed in both burn wound healing with a significantly decrease of the unhealed burn area and in cutaneous radiation. Moreover, MSCs have immunomodulation properties potentially effective in refractory acute and chronic graft versus host disease (GVHD) by improving thymic function and induction of Tregs. Indeed, MSCs are able to migrate to inflamed tissues after stimulation by pro-inflammatory cytokines and to modulate the local inflammatory reactions. MSCs have also demonstrated their ability to promote tissue remodelling, angiogenesis and immunomodulation through either differentiation or secretion of several growth factors such as VEGF, basic FGF and various cytokines. Therefore, combining their immunomodulation effect and secretion of soluble factors involved in wound repair, MSCs might be valuable as a cell therapy strategy for promoting cutaneous healing in SJS-TEN syndrome and subsequently decrease the morbi-mortality.