[Current dermatology guidelines in Germany-selected recommendations from 2021 and 2022]. / Aktuelle dermatologische Leitlinien in Deutschland ­ Ausgewählte Empfehlungen aus den Jahren 2021 und 2022.

Guidelines are systematically developed decision-making aids to ensure appropriate clinical care for specific medical conditions. In Germany, dermatological guidelines are developed under the aegis of the German Dermatological Society (DDG) and the Professional Association of German Dermatologists (BVDD), while European and international guidelines are published by organisations such as the European Centre for Guidelines Development (EuroGuiDerm), founded by the European Dermatology Forum (EDF) in cooperation with the Division of Evidence-Based Medicine at Charité-Universitätsmedizin Berlin. In 2021 and 2022, the German guidelines were revised or developed on topics such as the management of anticoagulation during dermatological procedures, chronic pruritus, contact dermatitis, laser therapy of the skin, psoriasis vulgaris, rosacea, extracorporeal photopheresis, onychomycosis, mucous membrane pemphigoid and prevention of skin cancer. A selection of the most important recommendations and innovations in the guidelines is summarized here.

[Current dermatology guidelines in Germany and Europe : A selection of clinically relevant recommendations]. / Aktuelle dermatologische Leitlinien in Deutschland und Europa : Eine praxisorientierte Übersicht ausgewählter Empfehlungen.

Clinical practice guidelines are systematically developed decision aids for specific medical conditions. In Germany, national dermatology guidelines are developed chiefly under the aegis of the German Dermatological Society in collaboration with the Professional Association of German Dermatologists. European and international dermatological guidelines also exist and are developed by a range of organisations, such as the European Centre for Guidelines Development, which was founded by the European Dermatology Forum in 2018. In the years 2019 and 2020, new or updated German national guidelines were published on topics such as pathological scars (hypertrophic scars and keloids), cutaneous lupus erythematosus, pyoderma grangrenosum, anal pruritus, anal eczema, anal canal and anal rim carcinomas, as well as the prevention of HPV-associated neoplasms through vaccination, syphilis and the systemic treatment of neurodermitis. A new European guideline on lichen planus closes a gap in the spectrum of guidelines available in Germany. Key recommendations and relevant changes in the guidelines are presented in this article.

Cryosurvival of in vitro produced bovine embryos supplemented with l-Carnitine and concurrent reduction of fatty acids.

Lipid accumulation is associated with reduced embryonic quality, causing limited survival after cryopreservation. Therefore, in the present study we aimed to reveal the effects of supplementation of a lipid reducing agent, l-carnitine and the removal of fatty acids during in vitro culture on the morphological as well as on the molecular level. To accomplish that, presumptive zygotes were cultured in 4 contrasting groups: namely SOFaa medium supplemented with BSA, (BSA), SOFaa medium supplemented with fatty acid free BSA (FAF), SOFaa medium supplemented with BSA as well as l-Carnitine (BSA + LC) and SOFaa medium concurrently supplemented with fatty acid free BSA and l-Carnitine (FAF + LC). Considering the developmental rates, no impact of different treatments was observed. Conversely, treatment groups clearly affected lipid content, with the lowest amounts detected in embryos derived from FAF and BSA + LC groups, implicating that both removal of fatty acids and supplementation of LC reduces lipid content effectively. Importantly, survival rates after cryopreservation show that LC significantly affects the kinetics of re-expansion, with the highest hatching rates detected for embryos cultured in FAF + LC (p < 0.05). Noteworthy, the highest cryotolerance did not go along with lowest lipid contents. Finally, metabolic alterations between the groups were reflected in different abundances of selected candidate genes related to lipid metabolism and oxidative stress response, like AMPKA1, ACC and PGC1 α or KEAP1 and SOD1. All in all, highly beneficial effects on survival rates after cryopreservation have been detected when embryos were cultured in absence of fatty acids and concurrent presence of l-Carnitine. Highest cryotolerance, however, did not correlate with lowest lipid contents.

[Rhinofacial conidiobolomycosis associated with cervical, thoracic and brachial localizations: one clinical case in Nigeria]. / Conidiobolomycose rhinofaciale avec localisations cervicales, thoraciques et brachiales: à propos d'un cas nigérian.

We report here the clinical case of a Nigerian adult patient who received medical care during October 2010, at the Center for Diagnosis and Treatment of Buruli ulcer in Pobè (Benin). He presented a massive facial tumor associated with several subcutaneous (cervical, thoracic and upper limbs) nodules, evolving since several years. Tissue samples collected at Pobè medical center were addressed to the mycology and histology laboratories of Angers University Hospital (France), according to the medical exchange agreement between the two institutions about the diagnosis and treatment of Buruli ulcer disease. Histological examination showed a Splendore-Hoeppli phenomenon, consisting of a granulomatous reaction made of eosinophilic polynuclear cells surrounding rare, large and irregular, non-septate hyphae. A filamentous fungus was isolated by cultivation of the clinical samples, which was identified as Conidiobolus coronatus. The patient was treated orally with daily doses of ketoconazole (400 mg per day). After 4 months of treatment, a marked regression of the facial lesion was obtained. A first constructive facial surgery was achieved, but the patient did not attend the second step. This case report allows us to remind the mycological diagnosis of this exotic mycosis, but also to emphasize the main difficulties encountered in medical management in the developing countries.

Analysis of correlation between mitotic index, MIB1 score and S-phase fraction as proliferation markers in invasive breast carcinoma. Methodological aspects and prognostic value in a series of 257 cases.

BACKGROUND: The study was designed in order to evaluate the degree of correlation of mitotic index (MI), Ki67 (MIB1) score and S-phase fraction (SPF) as markers of cell proliferation and prognosis in breast cancer. MATERIALS AND METHODS: The series analysed corresponded to 257 consecutive invasive breast carcinoma, treated at the Institut Curie, France, in 1995. Nottingham histological grade and MIB1 semiquantitative and quantitative score were assessed on histological sections, whereas SPF was calculated using flow cytometry analysis of fine-needle aspiration products. Proliferation indices were compared to pathological data and to overall survival (OS) and disease-free survival (DFS) (minimum follow-up: 72 months). RESULTS: The median values for the proliferation markers were 9/10 HPF for MI, 32.4% for MIB1 and 3.7% for SPF. A high rate of correlation (r=0.96; p<0.001) was observed between semi-quantitative and quantitative MIBI evaluation. A positive correlation was found between the three markers (r ranging from 0.54 to 0.61;p<0.001). Univariate analysis of markers associated to disease outcome showed that MIB1, axillary node status (N) and progesterone receptor (PR) status were significantly associated with OS and that MIB1 and SPF were associated with DFS, together with node and hormone receptor status. In multivariate analysis, when proliferation markers were adjusted on the N and PR status, only MIB1 retained a prognostic value for OS (RR= 1.83) [1.00;3.35] and SPF for DFS (RR= 1.58) [1.02-2.44] (p=0.04). CONCLUSION: A good level of correlation was observed between the values of the three markers of tumour cell proliferation analysed. In this series of invasive breast cancers, MIB1 immunostaining was found to be a prognostic marker of both OS and DFS. The median (32.4%) was a valuable cut-off value for prognostic assessment. Semi-quantitative and quantitative evaluations provided very similar values. MIB1 can thus be considered as a reliable prognostic maker, usable in small size tissue specimens which are inappropriate for MI or SPF analysis. The impact of MIB1 compared to that of the other proliferative markers will be further assessed in a subgroup of T1N0M0 for which the prognostic assessment is of major interest.

Autoantibodies within families of patients with systemic lupus erythematosus are not directed against the same nuclear antigens.

OBJECTIVE: The presence of antinuclear autoantibodies in systemic lupus erythematosus (SLE) is influenced by genetic factors. The presence of autoantibodies in healthy family members of patients has been reported. Our hypothesis was that autoantibodies are directed against the same antigens in first-degree family members of patients with SLE as in their patient relative. METHODS: Plasma was harvested from 50 patients with SLE, 154 unaffected first-degree family members, and 330 healthy controls. Presence of autoantibodies against 14 specific nuclear antigens was tested by the ELISA based line immunoassay INNO-LIA method. RESULTS: Seventy-four percent of patients, 32% of first-degree family members, and 1.5% of healthy controls had antibodies against any nuclear antigen. Most frequent autoantibodies in the patients were anti-histone and anti-SSA, whereas in the family members these were anti-RNP-C and anti-Topo-I/Scl. Presence and specificity of autoantibodies in family members were independent of the presence or absence of that autoantibody in their patient relative (chi-square p > 0.1 for all 14 antigens). CONCLUSION: Autoantibodies in family members and their patient relatives are not directed against the same nuclear antigens. Thus a familial aspecific dysfunction of the B lymphocyte is the most likely explanation for autoantibody production in SLE.

Frequency of major hemorrhage in patients treated with unfractionated intravenous heparin for deep venous thrombosis or pulmonary embolism: a study in routine clinical practice.

BACKGROUND: The rate of major hemorrhage during the initial treatment with unfractionated heparin (UFH) in patients with deep venous thrombosis (DVT) and pulmonary embolism (PE) in routine clinical practice is understudied. In recent clinical trials an overall average of 3.8% was reported. However, the incidence of this complication in routine patient care might be higher owing to less strict patient selection and lack of standardization in the administration of heparin. We have determined major bleeding rates during heparin treatment for DVT or PE in routine practice and compared these rates with data from clinical trials. METHODS: Data on the occurrence of major hemorrhage were retrieved according to strict criteria from the records of patients who had received continuous intravenous UFH therapy to treat objectively documented DVT or PE in 3 hospitals. RESULTS: After exclusion of 29 patients because of lack of objective diagnosis of DVT or PE and 25 patients because of initial treatment with low-molecular-weight heparin, 424 consecutive patients were available for detailed analysis. Among them, 17 patients (4.0%; 95% confidence interval, 2.1%-5.9%) experienced major hemorrhage during UFH treatment, which in most patients occurred at the end of planned heparin therapy; one of the hemorrhages was fatal. Six patients (1.4%; 95% confidence interval, 0.3%-2.5%) developed clinically suspected recurrent venous thromboembolism (fatal in 1 case) during UFH treatment or within 7 days' cessation. CONCLUSIONS: Administration of continuous intravenous UFH in patients with DVT or PE in routine clinical practice leads to a major bleeding rate of 4.0%. This rate is comparable to the rate of major bleeding in patients who received UFH in clinical trials. Our findings are relevant to the discussion of major bleeding rates in patients with DVT and PE treated in daily clinical practice with subcutaneous low-molecular-weight heparin and newer antithrombotic drugs.

A glycoprotein isolated from the sponge, Pachymatisma johnstonii, has anti-leishmanial activity.

A high anti-leishmanial activity was observed in an aqueous extract from the marine sponge Pachymatisma johnstonii, Bowerbank 1842 (Demospongiae, Geodiidae). Pachymatismin, a glycoprotein, was purified and shown to be a cytotoxic agent, which acts on promastigote and clinical-like amastigote stages with IC50 about 1 microg protein/ml and induces changes in the cell shape, phospholipase A2 activity and invasion capacity of the parasite. We believe pachymatismin is the first reported substance from a marine organism with anti-leishmanial activity.

Different microtubule network alterations induced by pachymatismin, a new marine glycoprotein, on two prostatic cell lines.

Pachymatismin is a new cytostatic factor extracted from the marine sponge Pachymatisma johnstonii Bowerbank. To investigate the mechanism of action of pachymatismin, we studied its effects on two human prostate cell lines (DU145 and E4) of tumor origin. Immunocytochemistry demonstrated that the drug caused depolymerization of microtubules in DU145 cells, this effect being similar to that of estramustine, known to be a microtubule-depolymerizing agent. E4 cells, described to be resistant to the microtubule-depolymerizing agent estramustine, were also found resistant to pachymatismin. Pachymatismin at the same dose that destroys microtubule organization in DU145 cells is not able to induce microtubule depolymerization in E4 cells. Compared to the estramustine- and pachymatismin-sensitive DU145 cells, E4 cells revealed an increase of betaI+II, betaIII, betaIV isotypes as well as post-translational modifications of tubulin, such as polyglutamylation and acetylation. In addition, the level of tau protein was also enhanced in E4 cells compared to DU145 cells. The effects of pachymatismin were tested in vitro using calf brain microtubules. It was shown that the drug lowers the capacity of microtubules to reassemble in vitro. Interestingly, pachymatismin has been found to inhibit microtubule assembly less efficiently when the ratio of tau to tubulin is increased. Taken together, pachymastismin has been shown to induce in vivo microtubule depolymerization following binding to microtubule proteins. Changes in microtubule components such as tubulin isoforms or tau may be involved in a decrease of sensitivity to pachymatismin.

In vivo effect of pachymatismin, a new marine glycoprotein, on a human non-small-cell lung carcinoma.

Pachymatismin is a novel glycoprotein extracted from a marine sponge, which has an antiproliferative effect in vitro on cells from a human non-small-cell bronchopulmonary carcinoma (NSCLC-N6). The drug blocks irreversibly the cells in the G0/G1 phase of the cell cycle. Here, we investigate the antitumor activity of pachymatismin against this cell line. Tumor growth was studied after three weeks treatment of nude mice by different doses of pachymatismin. A significant decrease in tumor growth was observed.

Effects in vitro of pachymatismin, a glycoprotein from the marine sponge Pachymatisma johnstonii, on a non-small-cell bronchopulmonary carcinoma line (NSCLC-N6).

Pachymatismin is a new cytostatic factor extracted from the marine sponge Pachymatisma johnstonii Bowerbank 1842 (Demospongiae, Geodiidae), which has an antiproliferative effect in vitro on cells from a human non-small-cell bronchopulmonary carcinoma (NSCLC-N6). The substance, both administered as a continuous and discontinuous treatment, triggers the irreversible arrest of cells in the G0/G1 phase of the cell cycle and morphological changes, thereby causing their destruction. Taken all together, these observations suggest that pachymatismin would induce atypical terminal cellular differentiation.