Ectodermal dysplasias: Classification and organization by phenotype,genotype and molecular pathway

An international advisory group met at the National Institutes of Health in Bethesda, Maryland in 2017, to discuss a new classification system for the ectodermal dysplasias (EDs) that would integrate both clinical and molecular information. We propose the following, a working definition of the EDs building on previous classification systems and incorporating current approaches to diagnosis: EDs are genetic conditions affecting the development and/or homeostasis of two or more ectodermal derivatives, including hair, teeth, nails, and certain glands. Genetic variations in genes known to be associated with EDs that affect only one derivative of the ectoderm (attenuated phenotype) will be grouped as non‐syndromic traits of the causative gene (e.g., non‐syndromic hypodontia or missing teeth associated with pathogenic variants of EDA “ectodysplasin”). Information for categorization and cataloging includes the phenotypic features, Online Mendelian Inheritance in Man number, mode of inheritance, genetic alteration, major developmental pathways involved (e.g., EDA, WNT “wingless‐type,” TP63 “tumor protein p63”) or the components of complex molecular structures (e.g., connexins, keratins, cadherins).     

G-CSF (Granulocyte Colony-Stimulating Factor): follow-up and use in a French University hospital

Granulocyte Colony-Stimulating Factor or G-CSF (NEUPOGEN) was approved for use in France in November 1991 for prevention of chemotherapy-induced neutropenia. This retrospective study was conducted at Saint-Louis Hospital, Paris, France, from November 1991 to March 1993 with a more detailed analysis of patient profiles for courses ordered between November 1991 and December 1992. Data were collected on standardized G-CSF-treatment summary forms. The purpose of the study was to define, in clinical terms, the patients treated by G-CSF to determine the average cost per course of therapy and its impact on the hospital pharmacy budget. From November 1991 to December 1992 data from 307 patient profiles were collected and analyzed. The subcutaneous route was the preferred route and only 16.6% of courses were administered intravenously. 45.6% of patients received a single course, 24.3% received two courses, and 30.1% received more than two courses. Each patient completed an average of 2.3 courses at an average cost per course of $2,000.00 (Canadian dollars). During March 1993, 50% of vials dispensed were administered to outpatients. During the 14-month period, an average of 613.8 vials were dispensed per month corresponding to an average monthly expenditure of $104,000.00 (Canadian dollars). In the first 12 months following the commercial availability of G-CSF, G-CSF expenditures accounted for 8% of the pharmacy budget.     

Duloxetine for the long-term treatment of Major Depressive Disorder in patients aged 65 and older: an open-label study

Background  

Late-life depression is a common, chronic and recurring disorder for which guidelines recommend long-term therapy. The safety and efficacy of duloxetine for the treatment of major depressive disorder (MDD) were evaluated using data from elderly patients (age ≥ 65 years; n = 101) who participated in a large, multinational, open-label study.     

Evaluating the Efficacy of Photodynamic Therapy with 20% Aminolevulinic Acid and Microdermabrasion as a Combination Treatment Regimen for Acne Scarring: A Split-face,Randomized, Double-blind Pilot Study

Acne scarring is a consequence of abnormal resolution of wound healing after damage that occurs in the sebaceous follicle during acne inflammation. No trial to date has evaluated the efficacy of the combination of microdermabrasion and photodynamic therapy for acne scarring. This single-center, double-blinded pilot study enrolled subjects with moderate-to-severe acne scarring who were randomly assigned in a blinded fashion to use aminolevulinic acid and vehicle in a split-face fashion after full-face treatment with microdermabrasion. On average, 80 percent of the patients displayed more improvement in scarring on the aminolevulinic acid split face versus the vehicle split face after five treatments. Using two different noninvasive mechanisms of targeting acne scarring provided for a safe treatment regimen characterized by more efficacious results with respect to higher rates of scarring improvement.Acne affects nearly 80 percent of adolescents and young adults. A recent community-based study of close to 800 subjects reported the overall acne scarring prevalence to be 14 percent in women and 11 percent in men.1 Severe scarring caused by acne is associated with substantial physical and psychological distress and has been associated with poor self-esteem, emotional debilitation, and lowered academic performance.2Acne scarring is a consequence of abnormal resolution of wound healing after damage that occurs in the sebaceous follicle during acne inflammation.3 The cause is due to either increased formation of tissue (hypertrophic scars or keloids) or damage to tissue (ice pick, rolling, and boxcar scars), leaving atrophic scars. All types of acne, from papulopustular to nodulocystic disease, can cause scarring; therefore, adequate treatment must be started early.4 Of the therapeutic approaches available for acne scarring, microdermabrasion represents a noninvasive efficacious treatment for contour irregularities. A molecular trial showed that after a single microdermabrasion treatment, matrix metalloproteinases involved in dermal remodeling and wound healing were upregulated in the biopsies taken from subjects with severe acne scarring.5Photodynamic therapy (PDT) involves the topical administration of aminolevulinic acid (ALA) and has been successfully utilized as a noninvasive treatment modality for acne. While not photosensitive by itself, ALA is converted by keratinocytes to protoporphyrin IX, which is a photosensitive compound that is activated by a blue light source. The reactive oxygen species formed in this reaction produce beneficial immunological changes. In the murine contact hypersensitivity model, PDT-ALA was found to cause local immunosuppression by decreasing the number of epidermal Langerhans cells, a finding which suggests that PDT has a potential immunological contribution to clinical efficacy for inflammatory diseases.Additionally, PDT has been shown to stimulate various matrix metalloproteinases, which may explain the collagen remodeling produced by this method. The side effect profile of topical ALA-PDT is extremely favorable, with mild pain and temporary cutaneous photosensitivity reported as the most frequent documented adverse effects. Many studies concerning the anti-inflammatory effects of PDT on acne have been published; however, a study specifically focusing on the use of PDT for acne scarring has yet to be conducted.No trial to date has evaluated the efficacy of the combination of microdermabrasion and ALA-PDT for acne scarring. However, targeting acne scarring with microdermabrasion followed by ALA-PDT appears to be logical. The authors hypothesize that the ability to increase the permeability barrier via the use of microdermabrasion will enhance the absorption of 5-ALA and thereby increase the efficacy of the combination treatment for acne scarring. They also hypothesize that utilizing microdermabrasion prior to application of ALA will speed the acid’s absorption, shortening the incubation time needed to 60 minutes, which could greatly enhance both patient convenience and physician productivity.The efficacy of the combination procedure may provide for a faster, yet longer-sustained clearance effect. In summary, by using two different mechanisms of targeting acne scarring, the authors expect to have more efficacious results with respect to higher rates of scarring improvement. They also hope to bring to the forefront a new therapeutic regimen for acne scarring, which combines two provider-applied modalities.     

Retapamulin 1% Ointment and Clobetasol Propionate 0.05% Foam is More Efficacious than Vehicle Ointment and Clobetasol 0.05% Propionate Foam in the Treatment of Hand/Foot Dermatitis: A Single Center,Randomized, Double-blind Study

Background: Staphylococcus aureus has been implicated in the pathogenesis of adult hand/foot dermatitis. Objective: The authors hypothesized that retapamulin 1% ointment and clobetasol propionate 0.05% foam would decrease disease severity in subjects with hand/foot dermatitis and provide a higher clearance of Staphylococcus aureus colonization, when compared to vehicle (placebo) ointment and clobetasol propionate 0.05% foam. Methods: Adult subjects with moderate to very severe hand/foot dermatitis had twice-daily topical application of clobetasol propionate 0.05% foam to hands/feet for 14 days and were randomized to apply either retapamulin 1% ointment or vehicle ointment twice daily to hands/feet and nares for five days. Results: Seventy-three percent of subjects in the retapamulin/clobetasol group were clear/almost clear at Day 15 compared to 47 percent of subjects in the vehicle/clobetasol group (p-value of 0.04). The percentage of subjects who had both negative skin and nares cultures and were clear/almost clear was also statistically significant in favor of the retapamulin/clobetasol group at Day 15 (p-value of 0.05). Limitations: Sample size, study population. Conclusion: At Day 15, retapamulin 1% ointment with clobetasol propionate 0.05% foam was more efficacious than vehicle ointment and clobetasol propionate 0.05% foam for disease improvement and Staphylococcus aureus clearance in adult subjects with hand/foot dermatitis.Hand/foot dermatitis (HFD) is a chronic disease with both genetic and environmental contributing risk factors.1 Several studies have implicated bacterial colonization, especially Staphylococcus aureus, as a pathogenic factor for eczematous lesions.2-4 Different mechanisms have been suggested to account for the increased S. aureus colonization. For example, the defective epidermal barrier in subjects with eczema allows S. aureus to invade these lesions and stimulate keratinocytes to release proinflammatory cytokines.5-9 In a recent study, which investigated the relationship between S. aureus and hand dermatitis, infection rates with S. aureus were found to be significantly higher in the disease cohort (48%) as compared to controls (8%). Furthermore, the presence of S. aureus correlated closely to disease severity.10 Another published clinical trial investigated the effect of treating S. aureus infection in children with generalized atopic dermatitis. The concomitant use of intranasal mupirocin and dilute bleach baths significantly decreased the severity of eczema in the treatment arm as compared to placebo. However, S. aureus carriage persisted in both skin and nares cultures.11 In a randomized, double-blind, placebo-controlled study of nasal carriers of S. aureus who applied retapamulin 1% ointment (Altabax®, Stiefel Laboratories) to both nostrils for five days, cultures carriage four weeks after treatment was negative for 86 percent of subjects.12 Thus, retapamulin 1% ointment offers the opportunity to effectively treat the presence of S. aureus in HFD. The primary purpose of this study was to investigate the use of retapamulin 1% ointment in combination with clobetasol propionate 0.05% foam for the treatment of HFD in adult subjects.     

What do error patterns in processing facial expressions,social interaction scenes and vocal prosody tell us about the way social cognition works in children with 22q11.2DS?

Impairments in social cognition have been frequently described in 22q11.2 deletion syndrome (22q11.2DS) and are thought to be a hallmark of difficulties in social interactions. The present study addresses aspects that are critical for everyday social cognitive functioning but have received little attention so far. Sixteen children with 22q11.2DS and 22 controls completed 1 task of facial expression recognition, 1 task of attribution of facial expressions to faceless characters involved in visually presented social interactions, and 1 task of attribution of facial expressions to characters involved in aurally presented dialogues. All three tasks have in common to involve processing of emotions. All participants also completed two tasks of attention and two tasks of visual spatial perception, and their parents completed some scales regarding behavioural problems of their children. Patients performed worse than controls in all three tasks of emotion processing, and even worse in the second and third tasks. However, they performed above chance level in all three tasks, and the results were independent of IQ, age and gender. The analysis of error patterns suggests that patients tend to coarsely categorize situations as either attractive or repulsive and also that they have difficulties in differentiating emotions that are associated with threats. An isolated association between the tasks of emotion and behaviour was found, showing that the more frequently patients with 22q11.2DS perceive happiness where there is not, the less they exhibit aggressive behaviour.