Cost-of-illness in psoriasis: Comparing inpatient and outpatient therapy

Treatment modalities of chronic plaque psoriasis have dramatically changed over the past ten years with a still continuing shift from inpatient to outpatient treatment. This development is mainly caused by outpatient availability of highly efficient and relatively well-tolerated systemic treatments, in particular BioLogicals. In addition, inpatient treatment is time- and cost-intense, conflicting with the actual burst of health expenses and with patient preferences. Nevertheless, inpatient treatment with dithranol and UV light still is a major mainstay of psoriasis treatment in Germany. The current study aims at comparing the total costs of inpatient treatment and outpatient follow-up to mere outpatient therapy with different modalities (topical treatment, phototherapy, classic systemic therapy or BioLogicals) over a period of 12 months. To this end, a retrospective cost-of-illness study was conducted on 120 patients treated at the University Medical Centre Mannheim between 2005 and 2006. Inpatient therapy caused significantly higher direct medical, indirect and total annual costs than outpatient treatment (13,042 € versus 2,984 €). Its strong influence on cost levels was confirmed by regression analysis, with total costs rising by 104.3% in case of inpatient treatment. Patients receiving BioLogicals produced the overall highest costs, whereas outpatient treatment with classic systemic antipsoriatic medications was less cost-intense than other alternatives

Prognostic value of immune cell infiltration, tertiary lymphoid structures and PD-L1 expression in Merkel cell carcinomas

Merkel cell carcinoma (MCC) is an aggressive, virus-associated, neuroendocrine tumor of the skin mainly affecting immunocompromised patients. Higher intratumoral infiltration with CD3 and CD8 positive T-cells is associated with a better prognosis, highlighting the relevance of the immune system for MCC development and progression. In this study 21 primary MCCs were stained with immune cell markers including CD3, CD4, CD8, CD68, CD20, and S100. Furthermore, tumor-infiltrating neutrophils, tertiary lymphoid structures and PD-L1 expression were analyzed and correlated with overall and recurrence free survival. All MCCs were Merkel Cell Polyomavirus positive. Overall and recurrence-free survival did not correlate with intra-and peritumoral CD3 and CD8 T-cell infiltration. In addition, no significant association regarding prognosis was found for tumor-associated neutrophils, tumor-associated macrophages or PD-L1 positivity in MCCs. Interestingly, the presence of tertiary lymphoid structures (TLS) in the tumor microenvironment significantly correlated with recurrence-free survival (P=0.025). In addition, TLS were significantly associated with a higher CD8/CD4 ratio in the tumor periphery (P=0.032), but not in the center of the tumor (P > 0.999). These results demonstrate for the first time that TLS, easily assessed in paraffin-embedded tissue in the tumor periphery of MCCs, may be a valuable prognostic factor indicating prolonged recurrence free survival

Process improvement microdisintegration when developing placer deposits of primorsky krai

Рассмотрены результаты энергодисперсионного микроанализа и акустических свойств глинистых пород, отобранных на участках комплексного месторождения Фадеевского рудно‐россыпного узла Приморского края. Отмечается, что углубление теоретических и экспериментальных исследований гидроактивации песков, инициирующих кавитационные эффекты, позволит решить важную проблему дезинтеграции золотосодержащих глинистых песков рудно‐россыпного типа

PARTICULARITIES OF ELECTROMAGNETIC SOUNDING TO ASSESS THE GEOLOGICAL STRUCTURE OF ROCK MASS

Статья посвящена исследованию законтурного состояния скальных пород участков рабочих уступов карьера «Железный» АО «Ковдорский ГОК». Приведены результаты электромагнитного зондирования слагающего уступ массива скальных пород совместно с визуальным и телеметрическим обследованием стенок буровых скважин. Предложены подходы по оценке структурной нарушенности пород рабочих уступов карьера электромагнитным зондированием.The article is devoted to the study of the beyond‐contour state of hard rocks in the working benches of the Zhelezny open pit, JSC Kovdorsky GOK. The results are pre‐sented of electromagnetic sounding of the rock mass composing a bench, together with vis‐ual and telemetric survey of borehole walls. Approaches are proposed for assessing the structural disturbance of the rocks in the working benches by electromagnetic sounding

Metal allergens nickel and cobalt facilitate TLR4 homodimerization independently of MD2

Development of contact allergy requires cooperation of adaptive and innate immunity. Ni(2+) stimulates innate immunity via TLR4/MD2, the bacterial LPS receptor. This likely involves receptor dimerization, but direct proof is pending and it is unclear if related haptens share this mechanism. We reveal Co(2+) as second metal stimulating TLR4 and confirm necessity of H456/H458 therein. Experiments with a new TLR4 dimerization mutant established dimerization as a mechanism of metal- and LPS-induced TLR4 activation. Yet, in interaction studies only LPS- but not metal-induced dimerization required MD2. Consistently, soluble TLR4 expressed without MD2 inhibited metal- but not LPS-induced responses, opening new therapeutic perspectives

Anti-Fouling Effects of Saponin-Containing Crude Extracts from Tropical Indo-Pacific Sea Cucumbers

Sea cucumbers are bottom dwelling invertebrates, which are mostly found on subtropical and tropical sea grass beds, sandy reef flats, or reef slopes. Although constantly exposed to fouling communities in these habitats, many species are surprisingly free of invertebrate epibionts and microfouling algae such as diatoms. In our study, we investigated the anti-fouling (AF) activities of different crude extracts of tropical Indo-Pacific sea cucumber species against the fouling diatom Cylindrotheca closterium. Nine sea cucumber species from three genera (i.e., Holothuria, Bohadschia, Actinopyga) were selected and extracted to assess their AF activities. To verify whether the sea cucumber characteristic triterpene glycosides were responsible for the observed potent AF activities, we tested purified fractions enriched in saponins isolated from Bohadschia argus, representing one of the most active anti-fouling extracts. Saponins were quantified by vanillin-sulfuric acid colorimetric assays and identified by LC-MS and LC-MS/MS analyses. We were able to demonstrate that AF activities in sea cucumber extracts were species-specific, and growth inhibition as well as attachment of the diatom to surfaces is dependent on the saponin concentration (i.e., Actinopyga contained the highest quantities), as well as on the molecular composition and structure of the present saponins (i.e., Bivittoside D derivative was the most bioactive compound). In conclusion, the here performed AF assay represents a promising and fast method for selecting the most promising bioactive organism as well as for identifying novel compounds with potent AF activities for the discovery of potentially novel pharmacologically active natural products

The transmembrane protein LRIG2 increases tumor progression in skin carcinogenesis

Over the last few decades, the number of cases of non‐melanoma skin cancer (NMSC) has risen to over 3 million cases every year worldwide. Members of the ERBB receptor family are important regulators of skin development and homeostasis and, when dysregulated, contribute to skin pathogenesis. In this study, we investigated leucine‐rich repeats and immunoglobulin‐like domains 2 (LRIG2), a transmembrane protein involved in feedback loop regulation of the ERBB receptor family during NMSC. LRIG2 was identified to be up‐regulated in various types of squamous cell carcinoma (SCC), but little is known about LRIG2 in cutaneous SCC (cSCC). To investigate the function of LRIG2 in cSCC in vivo, we generated a skin‐specific LRIG2 overexpressing transgenic mouse line (LRIG2‐TG) using the Tet‐Off system. We employed the 7,12‐dimethylbenz(a)anthracene/12‐O‐tetra‐decanoylphorbol‐13‐acetate (DMBA/TPA) two‐stage chemical carcinogenesis model and analyzed the skin during homeostasis and tumorigenesis. LRIG2‐TG mice did not exhibit alterations in skin development or homeostasis but showed an interaction between LRIG2 and thrombospondin‐1, which is often involved in angiogenesis and tumorigenesis. However, during carcinogenesis, transgenic animals showed significantly increased tumor progression and a more rapid development of cSCC. This was accompanied by changes in the ERBB system. After a single TPA application, inflammation of the epidermis was enhanced during LRIG2 overexpression. In human skin samples, LRIG2 expression was identified in the basal layer of the epidermis and in hair follicles of normal skin, but also in cSCC samples. In conclusion, epidermal LRIG2 excess is associated with activated EGFR/ERBB4‐MAPK signaling and accelerated tumor progression in experimentally induced NMSC, suggesting LRIG2 as a potential oncoprotein in skin

Дослідження структури порушених відкритою розробкою земель й пошук шляхів вдосконалення рекультивації залишкових виробок кар'єрів

Стаття присвячена дослідженням структури порушених земель, на ділянках з видобутку корисних копалин відкритим способом. Наведено площі порушень земель при розробці основних видів корисних копалин. Проаналізовано ризики, що виникають із несвоєчасною рекультивацією земель гірничого відводу, а також від покинутих гірничих виробок старих кар'єрів. Паралельно розглянуті обсяги відходів гірничого виробництва та їх повторне використання в якості заповнювача для залишкових вироблених просторів кар'єрів.The article is devoted to the research of land violation indicators at the extraction of minerals by surface mining method. Data gives about the land violations area at the mining key minerals. Ana-lyzed the risks from the not-on-time reclamation of the mining clam and abandoned excavations of the old quarries. In parallel considered the volumes of mining wastes and their reuse as aggregate for filling residual spaces of surface mines.Статья посвящена исследованиям площадей нарушения земель, связанных с добычей полезных ископаемых открытым способом. Приведены площади нарушений земель при разработке основных видов полезных ископаемых. Проанализированы риски, представляемые несвоевременной рекультивацией земель горного отвода, а также заброшенными горными выработками старых карьеров. Параллельно рассмотрены объемы отходов горного производства и их повторное использование в качестве заполнителя для остаточных выработанных пространств карьеров

Case Report: Effectiveness of deucravacitinib in chronic recurrent multifocal osteomyelitis and concomitant psoriasis

We present the case of a 22-year-old male who was first diagnosed with chronic recurrent multifocal osteomyelitis (CRMO) at the age of 16 years. During treatment with the tumor necrosis factor (TNF)-alpha inhibitor adalimumab, he developed severe palmoplantar psoriasis that affected his quality of life and necessitated discontinuation of the drug despite its efficacy against CRMO. Subsequent treatment with the interleukin (IL)-17a inhibitor secukinumab did not improve the psoriasis and led to a recurrence of the osteomyelitis. Therefore, the TYK-2 inhibitor deucravacitinib, approved in 2023 for the treatment of moderate to severe plaque psoriasis, was initiated. This resulted in clinical and morphological complete and sustained remission of CRMO within 12 weeks and a significant improvement of the psoriasis after six months of treatment with no occurrence of severe adverse events. To our knowledge, this is the first case report demonstrating complete and safe remission of CRMO associated with palmoplantar psoriasis treated with the TYK2 inhibitor deucravacitinib

Clinical and Serological Characterization of Orf-Induced Immunobullous Disease

Importance: Ecthyma contagiosum, or orf, is a viral zoonotic infection caused by Poxviridae. Although human orf infection is considered to follow a self-limited course, various immunological reactions may be triggered, including immunobullous diseases. In the majority of the latter cases, the antigenic target remained enigmatic. Objective: To characterize the predominant autoantigen in orf-induced immunobullous disease and further describe this clinical entity. Design, Setting, and Participants: This multicenter case series sought to provide detailed clinical, histopathological and immunological characteristics of a patient with orf-induced pemphigoid. Based on this index patient, serological analyses were conducted of 4 additional patients with previously reported orf-induced immunobullous disease. Immunoblotting with extracellular matrix and a recently established indirect immunofluorescence assay for detection of serum anti-laminin 332 IgG were performed. Exposures: The disease course and clinical characteristics of orf-induced immunobullous disease were observed. Main Outcomes and Measures: Orf-induced immunobullous disease is primarily characterized by anti-laminin 332 autoantibodies, predominant skin involvement, and a self-limiting course. The study provides further details on epidemiological, clinical, immunopathological, diagnostic, and therapeutic aspects of orf-induced immunobullous disease. Results: In all 5 patients, IgG1 and/or IgG3 autoantibodies against laminin 332 were identified. The α3, β3, and γ2 chains were recognized in 2, 4, and 1 patient(s), respectively. Conclusions and Relevance: In this case series, laminin 332, a well-known target antigen in mucous membrane pemphigoid, was a major autoantigen in orf-induced immunobullous disease, even though predominant mucosal lesions were lacking in this autoimmune blistering disease. Orf-induced anti-laminin 332 pemphigoid is proposed as distinct clinical entity