ß-Defensin 2 is a responsive biomarker of IL-17A-driven skin pathology in patients with psoriasis.

BACKGROUND: IL-17A is a key driver of human autoimmune diseases, particularly psoriasis. OBJECTIVE: We sought to determine the role of IL-17A in psoriasis pathogenesis and to identify a robust and measurable biomarker of IL-17A-driven pathology. METHODS: We studied 8 healthy subjects and 8 patients with psoriasis before and after administration of secukinumab, a fully human anti-IL-17A mAb, and used a combination of classical techniques and a novel skin microperfusion assay to evaluate the expression of 170 proteins in blood, nonlesional skin, and lesional skin. For validation, we also tested stored sera from 601 patients with a variety of autoimmune diseases. RESULTS: IL-17A was specifically expressed in lesional compared with nonlesional psoriatic skin (9.8 vs 0.8 pg/mL, P < .001). Proteomic and gene transcription analyses revealed dysregulated antimicrobial peptides, proinflammatory cytokines, and neutrophil chemoattractants, levels of which returned to normal after treatment with secukinumab. ß-Defensin 2 (BD-2) was identified as a biomarker of IL-17A-driven pathology by comparing protein expression in patients with psoriasis versus that in healthy subjects (5746 vs 82 pg/mL in serum, P < .0001; 2747 vs <218 pg/mL in dermis, P < .001), responsiveness to secukinumab therapy, and synergistic induction by IL-17A and TNF-α in epidermal keratinocytes. In a validation set of sera from 601 patients with autoimmune diseases thought to be IL-17A driven, we found that BD-2 levels are most highly increased in patients with psoriatic skin lesions, and in patients with psoriasis, BD-2 levels correlated well with IL-17A levels (r = 0.70, n = 199, P < .001) and Psoriasis Area and Severity Index scores (r = 0.53, n = 281, P < .001). CONCLUSION: IL-17A is a primary driver of skin pathology in patients with psoriasis, and serum BD-2 is an easily measurable biomarker of IL-17A-driven skin pathology.

A Case of Focal Small-cell Neuroendocrine Carcinoma in the Vicinity of the Extrahepatic Bile Duct, Adjacent to an Extensive Biliary Intraepithelial Neoplasm: A Diagnostic Challenge with Major Clinical Implications.

Gastroenteropancreatic neuroendocrine tumors are known for their aggressiveness. Diagnosis of various bile duct pathologies, like biliar intraepithelial neoplasm, mixed adenoneuroendocrine carcinomas or small cell carcinomas, is challenging. This case report focuses on a rare case of a focal primary minute small cell carcinoma in the vicinity of the extrahepatic bile duct, presenting itself next to an extensive biliar intraepithelial neoplasm. This finding led to adjuvant chemotherapy, followed by major surgery. Therapeutic approach was based on CT and MRI scans but most importantly on immunohistochemistry and histological evaluation. Initially CR seemed achievable, but metastases were to be found rapidly. The authors want to underline the fact that major clinical decisions are based on sometimes tiny specimens; as literature shows it is absolutely advisable to use markers to differentiate the dignity of investigated areas. The authors call for keeping collision of tumors in mind and adding KOC staining and using it in a routine manner examining biliary duct lesions.

New insights into oculodermal nevogenesis and proposal for a new iris nevus classification.

BACKGROUND/AIMS: To gain more knowledge about presence and dermatological associations of iris nevi as well as possible pathways involved in the formation of iris nevi. METHODS: We conducted a prospective, interdisciplinary observational study. Presence, morphology, topography of iris and cutaneous nevi as well as factors indicating sun-exposure were noted. RESULTS: A total of 632 participants including 360 (57%) women were examined. Of those, 26 subjects revealed 27 iris nevi. According to the current classification, all iris nevi were judged as solitary with the majority of them (n=20; 74%) located in the lower quadrants. In six (22.2%) cases we noted a peculiar 'incomplete sectoral pattern'; these nevi were located close to the pupil, were larger and had a more elongated, triangular shape compared with those located distant from the pupil, which appeared smaller and more roundish. Notably, five of these six peculiar (incomplete sectoral) iris nevi were located on the upper half of the iris. CONCLUSIONS: Based on our findings we propose classifying iris nevi into sectoral, incomplete sectoral and solitary subtypes. Additionally, we set up a hypothetic concept of oculodermal nevogenesis suggesting a time-dependent embryogenic alteration affecting the normal melanocyte location, migration and maturation along peripheral nerve sheets. Our new concept explains well the morphology and extension of benign melanocytic proliferations in the ocular region as well as their relation to uveal melanoma.

Complete recovery of a wide local reaction by the use of dexrazoxane 72 hours after epirubicin extravasation: case report and review of the literature.

BACKGROUND: Accidental extravasation of anthracyclines might result in devastating side effects and complications, including necrosis of tissue, with impairment of neighboring structures - most of them requiring surgery. Following recent approach guidelines, intravenous administration of dexrazoxane within 6 h after the event is recommended. CASE REPORT: We report on a 63-year-old female patient with breast cancer treated with epirubicin combination therapy. She experienced extravasation on the distal right arm at the end of the very first cycle, being initially treated with dimethylsulfoxide 99% topically. Clinical symptoms became worse. Despite the interval between the event and referral, dexrazoxane was given once daily for 3 days. She recovered completely without any sequelae. CONCLUSION: To our knowledge, this is the first case report of a successful treatment and complete recovery by the use of dexrazoxane even 3 days after extensive epirubicin extravasation. Additionally, a review of the literature is given.

Gender-specific outcome after implantation of low-contact-stress mobile-bearing total knee arthroplasty with a minimum follow-up of ten years.

PURPOSE: The study aim was an analysis of gender-specific outcome differences after implantation of the low-contact-stress (LCS) mobile-bearing total knee arthroplasty (TKA) with a minimum follow-up of ten years. METHODS: We retrospectively analysed 138 prostheses in 108 patients (82 women and 26 men) using our hospital database and a minimum follow-up of ten years (mean 14, range 11-23). Data was extracted with respect to quality of life, clinical outcome parameters [range of motion (ROM), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score, visual analogue scale (VAS), Knee Society Score (KSS), and complications. RESULTS: At follow-up, we observed no statistically significant differences in all outcome parameters between female and male patients after LCS TKA, except for VAS score, which revealed no clinical relevance due to the low difference (1.53 vs 1.03, p = 0.043). CONCLUSIONS: Ten years after implantation of the LCS TKA, gender did not influence its beneficial outcome.

Triple-negative breast cancer possibly transforming into malignant melanoma due to targeted therapy? A case report and review of literature.

BACKGROUND: Triple-negative breast cancer (TNBC) is characterized by lacking expression of estrogen receptor and progesterone receptor as well as absence of human epidermal growth factor receptor 2 overexpression and is an aggressive clinical phenotype. PATIENTS AND METHODS: We report the case of a 33-year-old woman who has been treated using a targeted approach for TNBC and developed a malignant melanoma metastasis without any primary. RESULTS AND CONCLUSION: Using targeted therapies, tumors can be treated much more effectively, but up to now, we do not know much about potential adverse reactions. Due to the targeted therapy, tumors may be pressurized for transformation. We call for further investigations to rule out the potential risks of targeted therapy in TNBC. This is the first report of a potential transforming of one tumor entity to another by a targeted therapy.

Effect of platelet-rich plasma on the biologic activity of the human rotator-cuff fibroblasts: A controlled in vitro study.

To assess the in vitro effect of platelet-rich plasma (PRP) on biological activity of the human rotator cuff fibroblasts and to describe the optimal dose-response to maximize cellular stimulation while reducing potential risk. Rotator cuff (RC) fibroblasts of n = 6 patients (mean age of 65.2 years) undergoing arthroscopic cuff tear reconstruction were cultured in vitro for 21 days and stimulated with PRP in three different concentrations (1-, 5-, and 10-fold). Samples were obtained for DNA and GAG measurement at 1, 7, 14, and 21 days. The biological outcomes were regressed on the PRP concentration. The application of PRP significantly influenced the fibroblast proliferation and activity of the human rotator cuff with elevated glycosaminoglycan (GAG) and DNA levels. The dosage of PRP had the significantly highest impact on this proliferation using a onefold or fivefold application. PRP has a significant effect on fibroblast proliferation of the human rotator cuff in vitro with an optimal benefit using a onefold or fivefold PRP concentration. This study justifies further in vivo investigations using PRP at the human rotator cuff.

Clinical overview of cutaneous features in hypereosinophilic syndrome.

The hypereosinophilic syndromes (HES) are a heterogeneous group of disorders defined as persistent and marked blood eosinophilia of unknown origin with systemic organ involvement. HES is a potentially severe multisystem disease associated with considerable morbidity. Skin involvement and cutaneous findings frequently can be seen in those patients. Skin symptoms consist of angioedema; unusual urticarial lesions; and eczematous, therapy-resistant, pruriginous papules and nodules. They may be the only obvious clinical symptoms. Cutaneous features can give an important hint to the diagnosis of this rare and often severe illness. Based on advances in molecular and genetic diagnostic techniques and on increasing experience with characteristic clinical features and prognostic markers, therapy has changed radically. Current therapies include corticosteroids, hydroxyurea, interferon-α, the tyrosine kinase inhibitor imatinib mesylate, and (in progress) the monoclonal anti-interleukin-5 antibodies. This article provides an overview of current concepts of disease classification, different skin findings, and therapy for HES.

Sex-related outcome differences after implantation of low-contact-stress mobile-bearing total knee arthroplasty.

PURPOSE: The aim of the study was to investigate outcome differences between female and male patients after implantation of low-contact-stress (LCS) mobile-bearing total knee prostheses at a minimum follow-up of five years with respect to clinical and radiological parameters. METHODS: We retrospectively analysed 128 prostheses in 126 patients (90 women and 34 men) using our hospital database. Data was extracted with respect to range of motion (ROM), the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score, the Knee Society Score (KSS) and radiolucent lines on conventional X-rays. RESULTS: At follow-up, we observed no significant differences between female and male patients after LCS total knee prostheses. Benefit after implantation of LCS total knee prostheses after five years of minimum follow-up was not significantly different between female and male patients in terms of clinical outcome or radiolucent lines. CONCLUSIONS: We found no factors in favour of gender-specific total knee prostheses.

Pseudomonas oryzihabitans cutaneous ulceration from Octopus vulgaris bite: a case report and review of the literature.

BACKGROUND: Octopus vulgaris is a common marine animal that can be found in nearly all tropical and semitropical waters around the world. It is a peaceful sea dweller with a parrotlike beak, and its primary defense is to hide through camouflaging adjustments. Bites from animals of the class Cephalopoda are very rare. We describe a boy who was bitten on his forearm by an Octopus vulgaris. OBSERVATION: A 9 -year-old boy was bitten by an Octopus vulgaris while snorkeling. There was no strong bleeding or systemic symptoms; however, 2 days later, a cherry-sized, black, ulcerous lesion developed, surrounded by a red circle that did not heal over months and therefore had to be excised. Histologic examination showed ulceration with extensive necrosis of the dermis and the epidermis. A microbial smear revealed Pseudomonas (formerly known as Flavimonas) oryzihabitans. After excision, the wound healed within 2 weeks, without any complications or signs of infection. CONCLUSIONS: To the best of our knowledge, this case represents the first report of an Octopus vulgaris bite resulting in an ulcerative lesion with slow wound healing owing to P oryzihabitans infection. We recommend greater vigilance regarding bacterial contamination when treating skin lesions caused by marine animals.