Analysis of the German DRG data for livedoid vasculopathy and calciphylaxis.

BACKGROUND: Livedoid vasculopathy and calciphylaxis are rare skin disorders. Large cohorts of patients have been missing so far for detailed analysis. PATIENTS AND METHODS: Data from diagnosis-related groups (DRGs) of hospitalized cases of livedoid vasculopathy (ntotal = 1357) and calciphylaxis (ntotal = 699) were analysed for the years 2008-2013 concerning sex, age and frequency of diagnosis. To avoid deviations to non-relevant secondary diagnosis and due to changes in ICD-10 indices, we selected the two most recent available years 2013 and 2014 for evaluation of the accompanying diagnoses for both, livedoid vasculopathy (n = 519) and calciphylaxis (n = 324). Those were additionally evaluated as possible comorbidity. RESULTS: The male-female ratio for livedoid vasculopathy was 2.1:1. Patients older than 45 years comprehended 74.7% of all patients with peaks between the ages of 45-50 and 70-75. Livedoid vasculopathy patients suffered from cardiovascular and renal diseases. Coding of coagulation disorders was found rarely in our analysis. For calciphylaxis, we calculated a male-female ratio of 1.7:1. Most of the patients were at an age between 65 and 80 years. Diagnosis at an age under 35 years was rare. In general, most calciphylaxis patients showed end-stage renal disease with need of dialysis and presented with the resulting complications. CONCLUSIONS: Our data analysis shows relevant comorbidity and cofactors of these rare diseases like livedoid vasculopathy and calciphylaxis in Germany by a large number of cases.

[Importance of biopsy in the diagnostic assessment of chronic wounds-position paper of the Initiative Chronische Wunden (ICW) e. V.] / Stellenwert der Biopsie in der Diagnostik chronischer Wunden ­ ein Positionspapier der Initiative Chronische Wunden (ICW) e. V.

Diagnostic assessment of chronic wounds is essential for the initiation of causal therapeutic treatment. For diagnostic classification of the wound genesis, it may be necessary to take a tissue sample for histological and/or microbiological processing. If there is clinical suspicion of a specific cause of the wound such as a neoplasm, an inflammatory dermatosis or a pathogen-induced wound, a tissue sample for further diagnosis is required immediately. If the ulceration does not respond sufficiently to adequate causal therapy, a tissue sample for further evaluation is recommended after 12 weeks. The choice of the correct sampling technique, further storage, transport and processing are just as decisive for a reliable result as the specific question for the diagnostic laboratory.

[The term mixed leg ulcer should no longer be used today]. / Der Begriff Ulcus cruris mixtum sollte heute nicht mehr verwendet werden.

A wound on the lower legs of patients with chronic venous insufficiency (CVI) and peripheral arterial disease (PAD) is today usually referred to as a mixed leg ulcer. This does not take into account the different stages of the diseases and, thus, their pathophysiological relevance. In everyday clinical practice, this often leads, among other things, to these patients not receiving compression therapy. The multidisciplinary professional association Initiative Chronische Wunden (ICW) e. V., therefore, recommends that this undifferentiated and misleading term should no longer be used. Instead, a leg ulcer with advanced CVI and concomitant PAD in stage I-IIb according to Fontaine or Rutherford category 0-3 should be classified as a venous leg ulcer, while a leg ulcer with advanced PAD in stage III or IV according to Fontaine or Rutherford category 4-6 and advanced CVI is termed an arteriovenous leg ulcer. A leg ulcer in advanced PAD stage IV according to Fontaine or Rutherford category 5 or 6 without advanced CVI is called an arterial leg ulcer. Other relevant comorbidities with an influence on wound healing should also be described separately.

Verrucous carcinoma in epidermolysis bullosa simplex is possibly associated with a novel mutation in the keratin 5 gene.

Epidermolysis bullosa simplex (EBS) is mainly caused by mutations in the KRT5 and KRT14 genes. Squamous cell carcinoma (SCC) represents the second most frequent skin neoplasia with complex aetiology. The molecular events disrupting the orchestrated interplay between the cytoskeleton, cell adhesion molecules and signalling proteins are ill understood in SCC. We describe the molecular background and the unusual course of the disease in a patient with EBS Dowling-Meara, severe keratoderma and a massive verrucous carcinoma. Skin and tumour samples from the patient were analysed using light microscopy, immunohistochemistry and immunofluorescence mapping. Mutation analysis of the KRT5 and KRT14 genes identified the novel KRT5 mutation p.E477D. Invasive tumour areas were characterized by downregulation of keratins 5 and 14, reduced and irregular desmocollin-2 expression and increased expression of keratins 6, 16 and 17. Levels of Ki-67 were increased and levels of E-cadherin strongly reduced in the tumour tissue. In this case a novel KRT5 mutation led to increased fragility of keratinocytes. Desmosome and adherens junctions were destabilized, which may trigger keratinocyte-mediated inflammation, possibly via p120-catenin-dependent signalling, suggesting a link between a keratin mutation and SCC, which adds weight to the hypothesis that disturbance of the cytoskeleton represents a major cause in the appearance of the malignant phenotype. Some individuals with EBS may be at risk of developing secondary SCC.

[Digital and innovative teaching in dermatology : Practically oriented teaching online]. / Digitale und innovative Lehre in der Dermatologie : Praktisch orientierte Lehre online.

BACKGROUND: Due to the corona pandemic and also to the new competence-oriented catalogue of learning objectives in medicine and the master plan for medical studies 2020, the development of digital and practical teaching concepts has experienced a great increase in importance. AIM OF THE WORK: As a result of this development, it was an important task to establish this combination and incorporate it into the curricular teaching process. MATERIAL AND METHODS: The "Toolkit dermatology" was established, which was sent to a total of more than 650 students at German university dermatology clinics. Using educational films, the students were able to practice their skills. In a further development, the toolkit was combined with classroom lectures and the students were asked to evaluate the toolkit online. RESULTS: The vast majority of students (95-100%) clearly stated that the toolkit helped them to develop their practical skills. Some of them were in fact motivated to complete a clinical traineeship/practical tertial year in dermatology (21-88%). The combination of toolkit and subsequent classroom teaching was also rated very positively (82.2%), as this hybrid mode of teaching provided a better understanding. DISCUSSION: Digital teaching formats as part of the concept of blended learning, i.e. the combination of virtual and analogue teaching formats, are becoming increasingly more important. Solutions for the disadvantages, such as the lack of real interaction and suitable examination formats, still remain to be found; however, the toolkit project demonstrates that hands-on and digital teaching can lead to high student motivation as well as a high educational standard.

Fatty acid composition in chronic heart failure: low circulating levels of eicosatetraenoic acid and high levels of vaccenic acid are associated with disease severity and mortality.

OBJECTIVES: Free fatty acids (FFAs) are the major energy sources of the heart, and fatty acids (FAs) are active components of biological membranes. Data indicate that levels of FAs and their composition may influence myocardial function and inflammation. The aim of this study was to investigate whether total levels and composition of FAs and FFAs in plasma are altered in clinical heart failure (HF) and whether any alterations in these parameters are correlated with the severity of HF. SUBJECTS: Plasma from 183 patients with stable HF was compared with plasma from 44 healthy control subjects. RESULTS: Our main findings are as follows: (i) patients with HF had decreased levels of several lipid parameters and increased levels of FFAs in plasma, compared with controls, which were significantly correlated with clinical disease severity. (ii) Patients with HF also had a decreased proportion in the plasma of several n-3 polyunsaturated FAs, an increased proportion of several monounsaturated FAs, and a decreased proportion of some readily oxidized long-chain saturated FAs. (iii) These changes in FA composition were significantly associated with functional class, impaired cardiac function (i.e., decreased cardiac index and increased plasma N-terminal pro-B-type natriuretic peptide levels) and enhanced systemic inflammation (i.e., increased high-sensitivity C-reactive protein levels). (iv) Low levels of C20:4n-3 (eicosatetraenoic acid) and in particular high levels of C18:1n-7 (vaccenic acid) were significantly associated with total mortality in this HF population. CONCLUSIONS: Our data demonstrate that patients with HF are characterized by a certain FA phenotype and may support a link between disturbed FA composition and the progression of HF.

Malignant tumours arising in chronic leg ulcers: three cases and a review of the literature.

The precancerous potential of chronic leg ulcers is well-established but the number of reported cases overall is small. Delay in diagnosis may result in a worse prognosis, loss of the affected limb or occurrence of metastases. We report a case series of three patients with long-standing history of recalcitrant leg ulcers, which finally showed malignancy when histologically investigated. In addition, we discuss the literature concerning malignant transformation of chronic leg ulcers and try to bring forward the controversial question of how to differentiate primary and secondary malignancies in chronic ulcers. Although hypotheses about altered wound healing mechanisms, influence of chronic inflammation and irritation or tissue damage through infections are conclusive, further investigations are necessary to clarify the exact pathogenetic mechanisms of tumour development in chronic wounds.

Dirt-binding particles consisting of hydrogenated castor oil beads constitute a nonirritating alternative for abrasive cleaning of recalcitrant oily skin contamination in a three-step programme of occupational skin protection.

BACKGROUND: In occupational fields with exposure to grease, oil, metal particles, coal, black lead or soot, cleansing formulations containing abrasive bodies (e.g. refined walnut shell, corn, wood, plastic or pumice) are used. These may constitute an irritant per se. As an alternative, hydrogenated castor oil (also known as castor wax) beads have been developed as dirt-binding particles. A polar surface contributes to their mechanical cleaning effects in removal of oily grime. OBJECTIVES: Standardized examination of the in vivo effects upon the skin barrier of castor wax beads in comparison with abrasive bodies and pure detergent. METHODS: Three cleansing preparations - (i) detergent, (ii) detergent containing castor wax beads, (iii) detergent containing walnut shell powder - were each repetitively applied in vivo (four times daily for 3 weeks), mimicking workplace conditions, in 30 healthy volunteers (15 with and 15 without an atopic skin diathesis) and compared vs. (iv) no treatment. The treatment effects upon the skin barrier were monitored by repeated measurements of functional parameters [transepidermal water loss (TEWL), redness] and surface topography. RESULTS: After a 3-week treatment, a significant global treatment effect (P < 0.0001) was found in the atopic group concerning TEWL as indicator for barrier function. A significantly higher TEWL and increasing erythema in the area treated with detergent containing walnut shell powder reflected its irritant effect compared with castor wax beads dispensed in the identical detergent. Cleaning properties of the two formulas were comparably superior to detergent alone. CONCLUSIONS: Castor wax beads constitute a novel nonirritating alternative for abrasive cleaning of recalcitrant oily skin contamination appropriate for individuals with an atopic skin diathesis in a three-step programme of occupational skin protection. As the skin barrier may additionally be influenced by the composition of dirt and use of skin protection and skin care measures under real workplace conditions, this component may now be used and examined further in different occupations.

Reduction in the appearance of facial hyperpigmentation after use of moisturizers with a combination of topical niacinamide and N-acetyl glucosamine: results of a randomized, double-blind, vehicle-controlled trial.

BACKGROUND: Topical niacinamide and N-acetyl glucosamine (NAG) each individually inhibit epidermal pigmentation in cell culture. In small clinical studies, niacinamide-containing and NAG-containing formulations reduced the appearance of hyperpigmentation. OBJECTIVES: To assess the effect of a combination of niacinamide and NAG in a topical moisturizing formulation on irregular facial pigmentation, including specific detection of changes in colour features associated with melanin. METHODS: This was a 10-week, double-blind, vehicle-controlled, full-face, parallel-group clinical study conducted in women aged 40-60 years. After a 2-week washout period, subjects used a daily regimen of either a morning sun protection factor (SPF) 15 sunscreen moisturizing lotion and evening moisturizing cream each containing 4% niacinamide + 2% NAG (test formulation; n = 101) or the SPF 15 lotion and cream vehicles (vehicle control; n = 101). Product-induced changes in apparent pigmentation were assessed by capturing digital photographic images of the women after 0, 4, 6 and 8 weeks of product use and evaluating the images by algorithm-based computer image analysis for coloured spot area fraction, by expert visual grading, and by chromophore-specific image analysis based on noncontact SIAscopy for melanin spot area fraction and melanin chromophore evenness. RESULTS: By all four measures, the niacinamide + NAG formulation regimen was significantly (P < 0.05) more effective than the vehicle control formulation regimen in reducing the detectable area of facial spots and the appearance of pigmentation. CONCLUSIONS: A formulation containing the combination of niacinamide + NAG reduced the appearance of irregular pigmentation including hypermelaninization, providing an effect beyond that achieved with SPF 15 sunscreen.

[Melanoma and pregnancy]. / Melanom und Schwangerschaft.

The incidence of melanoma has steadily increased in recent years. As women of childbearing age are also increasing being affected, questions about birth control, hormonal contraception and necessary procedures in case of pregnancy are spotlighted when counseling this group of patients. A potentially adverse effect of pregnancy on melanoma risk and prognosis has been discussed for decades. Giving advice to pregnant melanoma patients concerning diagnostic and therapeutic decisions often requires interdisciplinary collaboration of the treating clinicians, especially in cases of progressive metastatic disease.

Practices for managing a flare of long-standing rheumatoid arthritis: survey among French rheumatologists.

OBJECTIVE: To describe the practices of rheumatologists in France for managing a flare in a patient being treated for long-standing rheumatoid arthritis (RA) and to estimate the corresponding costs. METHODS: A survey questionnaire was sent to the 2485 practicing rheumatologists in France; 917 completed questionnaires were returned (37% response rate). The questionnaire collected information on the respondents and on their recommendations for managing a fictional patient with a 10-year history of RA in flare, with a recent episode of neck pain, despite prednisone and methotrexate therapy. Investigational and treatment (first month) costs were estimated from the perspective of society in 2001 Euros. RESULTS: Over 80% of the respondents recommended measuring laboratory inflammation parameters, complete blood cell counts, liver enzymes, serum creatinine, and radiographs (hands, anteroposterior cervical spine view, wrists, knees); 50-70% recommended additional cervical spine incidences, elbow and chest radiographs, and bone absorptiometry. Adding anti-TNF therapy (24%) or another DMARD (10%), increasing the methotrexate dosage (24%), and substituting leflunomide for methotrexate were the main recommended treatments. Most respondents suggested continuing the glucocorticoid in the same dosage (61%) or a higher dosage (36%). Analgesics and non-steroidal anti-inflammatory drugs were recommended by 65% and 41% of respondents and rehabilitation therapy by 83%. The median cost was 500 Euro (mean 1105 Euro; range 80-4089 Euro). CONCLUSION: We found a high level of agreement among French rheumatologists regarding the evaluation of established RA. Marked variations in recommended treatments were observed and translated into major cost differences.

Topical palmitoyl pentapeptide provides improvement in photoaged human facial skin.

The palmitoyl pentapeptide palmitoyl-lysine-threonine-threonine-lysine-serine (pal-KTTKS) is a synthetic material that was designed as a topical agent to stimulate collagen production and thus provide a skin anti-wrinkle benefit. To determine if pal-KTTKS is effective, the clinical study reported here was conducted. Caucasian female subjects (n = 93, aged 35-55) participated in a 12-week, double-blind, placebo-controlled, split-face, left-right randomized clinical study assessing two topical products: moisturizer control product vs. the same moisturizer product containing 3 ppm pal-KTTKS. Pal-KTTKS was well tolerated by the skin and provided significant improvement vs. placebo control for reduction in wrinkles/fine lines by both quantitative technical and expert grader image analysis. In self-assessments, subjects also reported significant fine line/wrinkle improvements and noted directional effects for other facial improvement parameters.

Absence of bleeding complications in patients undergoing cortical surgery while receiving valproate treatment.

Valproate (VPA) is associated with a variety of idiosyncratic hematological effects including thrombocytopenia, inhibition of platelet aggregation, and fibrinogen depletion. This has led some investigators to recommend discontinuation of VPA therapy prior to elective surgical procedures. However, administration of VPA therapy is not altered prior to surgery at the authors' center and no VPA-associated bleeding complications have been observed. Therefore, a retrospective chart review was conducted to verify the clinical observations in patients who had undergone cortical resection while receiving antiepileptic drugs (AEDs). Baseline, surgical, and postoperative laboratory data were available for a total of 313 patients, 111 of whom were receiving VPA and 202 of whom were receiving AEDs without VPA (control patients). Eighty-seven percent of the patients receiving VPA were also being treated with at least one other AED. The control group was approximately equally divided between monotherapy (55%) and polytherapy (45%) treatments. Platelet counts were significantly lower in the control polytherapy (284 +/- 74 x 10(9)/L) and both VPA groups (279 +/- 113 x 10(9)/L) as compared with the control monotherapy group (314 +/- 85 x 10(9)/L). Baseline fibrinogen levels were significantly lower in the VPA than in the control groups (223 +/- 91 g/dl vs. 278 +/- 95 g/dl). Both pre- and postoperatively, the VPA group had lower red blood cells counts, hematocrit, and hemoglobin levels. There was no significant difference between groups in estimated blood loss during surgery or qualitative wound discharge postsurgery. There was only one case of a bleeding complication, which occurred 14 days postoperatively in a patient receiving carbamazepine monotherapy. The results of this study confirm the clinical observations of an absence of bleeding complications in patients receiving VPA therapy at the time of surgery, despite differences in laboratory parameters.

Survey of practices regarding management of early rheumatoid arthritis by rheumatologists in France.

OBJECTIVE: To describe the practices of rheumatologists in France regarding the initial management of early rheumatoid arthritis (RA) and to estimate the associated costs. METHODS: A questionnaire on the diagnosis and treatment of early RA was sent to the 2485 practicing rheumatologists in France. The results of the 917 completed questionnaires (37% response rate) were analyzed, and initial investigation and treatment costs, including the first month of treatment, were calculated from a socio-economic perspective. RESULTS: For the RA diagnosis, more than 80% of the respondents recommended the erythrocyte sedimentation rate, C-reactive protein, complete blood count, rheumatoid factor, antinuclear antibody and wrist radiographs. In 40% and 60% of the cases, antikeratin antibody, liver enzymes, serum creatine, serum protein electrophoresis and radiographs (chest, foot and knee) were advocated. Initial drugs administered were non-steroidal antiinflammatory agents (88%), analgesics (76%), disease modifying anti-rheutmatic drugs (74% with methotrexate in 46% of cases, followed by hydroxychloroquine [13%], sulfasalazine [8%], leflunomide [7%], intramuscular gold therapy [6%]), and glucocorticoids (21%). Rehabilitation was recommended by 51% of the respondents. The median cost for this initial management was 273 euros (mean 301 euros, range 49-1,336 euros). CONCLUSION: Marked variations occur among French rheumatologists in the initial management of early RA. These data may be helpful in identifying obstacles to physician compliance with recommendations regarding everyday clinical practice and to set up more a specific evaluative study.

The effect of antibacterial soap with 1.5% triclocarban on Staphylococcus aureus in patients with atopic dermatitis.

This double-blind study determined whether daily bathing with an antibacterial soap would reduce the number of Staphylococcus aureus on the skin and result in clinical improvement of atopic dermatitis. For 9 weeks, 50 patients with moderately severe atopic dermatitis bathed daily with either an antimicrobial soap containing 1.5% triclocarban or the placebo soap. They also used a nonmedicated moisturizer and 0.025% triamcinolone acetonide cream as needed, but the availability of the corticosteroid cream was discontinued after 6 weeks. The antimicrobial soap regimen caused significantly greater improvement in the severity and extent of skin lesions than the placebo soap regimen, which correlated with reductions both in S aureus in patients with positive cultures at baseline and in total aerobic organisms. Outcome measures included reductions in S aureus, total aerobic organisms, and dermatologic assessments. Overall, daily bathing with an antibacterial soap was well tolerated, provided clinical improvement, and reduced levels of skin microorganisms.