Introduction
The broad and sustained efficacy of apremilast for psoriasis has been demonstrated in randomized and real-world observational studies. Data from Central and Eastern Europe (CEE) are ...lacking. Moreover, apremilast use in this region is limited by country-specific reimbursement criteria. This is the first study to report data on the real-world use of apremilast in the region.
Methods
APPRECIATE (NCT02740218) was an observational, retrospective, cross-sectional study assessing psoriasis patients 6 (± 1) months after apremilast treatment initiation. The study aimed to describe the characteristics of patients with psoriasis receiving apremilast, estimate treatment outcomes, including Psoriasis Area Severity Index (PASI), Body Surface Area (BSA), and Dermatology Life Quality Index (DLQI), and assess dermatologists' and patients' perspectives on treatment using questionnaires including the Patient Benefit Index (PBI). Adverse event reports were taken from the medical records.
Results
Fifty patients (Croatia: 25; Czech Republic: 20; Slovenia: 5) were enrolled. In patients continuing apremilast at 6 (± 1) months, mean (± SD) PASI score was reduced from 16.2 ± 8.7 points at treatment initiation to 3.1 ± 5.2 at 6 (± 1) months; BSA from 11.9% ± 10.3% to 0.8% ± 0.9%; DLQI from 13.7 ± 7.4 points to 1.6 ± 3.2. PASI 75 was reached by 81% of patients. Physicians reported that the overall treatment success fulfilled their expectations in more than two thirds of patients (68%). At least three-quarters of patients reported apremilast had a quite or very high benefit on the needs they identified as being most important. Apremilast was well tolerated; no serious or fatal adverse events were identified.
Conclusion
Apremilast was effective in reducing skin involvement and improving quality of life in CEE patients having severe disease. Treatment satisfaction among physicians and patients was very high. These data add to the growing body of evidence showing consistent effectiveness of apremilast across the continuum of psoriasis disease severity and manifestations.
Trial registration
ClinicalTrials.gov identifier, NCT02740218.
Psoriasis is one of the most common chronic inflammatory skin disorders worldwide with a significant number of patients suffering from moderate to severe disease and requiring systemic therapy. Over ...the past two decades, better knowledge of disease pathophysiology has translated into treatment advances for both primary disease and its associated comorbidities. However, it is important to review the use of biologic or targeted therapy in a clinical setting in order to understand how to optimize therapeutic results and recognize any unmet needs in this patient subpopulation. We conducted a retrospective study on a cohort of patients diagnosed with psoriasis that had received at least one dose of biologic or targeted therapy for the treatment of psoriasis at the Rijeka Clinical Hospital Center. By documenting treatment trends and specific patient characteristics, we will be able to address any unmet needs in this patient population and provide individualized care strategies.
Abstract Psoriasis is a chronic papulosquamous skin disease, histologically characterized by epidermal hyperproliferation and dermal infiltration of inflammatory cells. The majority of T lymphocytes ...infiltrating dermis are CD4+ T lymphocytes secreting type 1 and type 17 cytokines. These cytokines are responsible for triggering keratinocyte proliferation as well as chemokine secretion and subsequent migration of other inflammatory cells in the skin. Contrarily, lymphocytes that accumulate in epidermis are mainly CD8+ T lymphocytes. According to the recent findings, these cells can also secrete type 1 and type 17 cytokines. However, it is demonstrated so far that epidermal CD8+ T lymphocytes contain higher amounts of cytolytic molecules, such as perforin, granzyme B and granulysin whose role in psoriasis pathogenesis is still unknown. Therefore, in this article we hypothesize the active involvement of cell mediated cytotoxicity in killing the proliferating keratinocytes as a mechanism of potential self-defense and possible brake in psoriatic plaque formation, maintaining skin homeostasis.
Background: Tumor necrosis factor‐like weak inducer of apoptosis (TWEAK) has been implicated in the pathogenesis of various inflammatory pathologies and cancer. We aimed to investigate its expression ...in normal human skin, inflammatory skin diseases and epidermal neoplasms.
Methods: Immunohistochemistry for TWEAK was performed in samples of healthy skin, plaque psoriasis, lichen planus, prurigo nodularis, discoid lupus erythematosus, lichen sclerosus, seborrheic keratosis, common warts, actinic keratosis, Bowen's disease, keratoacanthoma and basal and squamous cell carcinoma. Double immunofluorescence was used to investigate co‐localization of TWEAK with cytokeratin‐10 and proliferating cell nuclear antigen (PCNA).
Results: TWEAK was robustly expressed in the epidermis of healthy skin and decreased in inflammatory conditions, both in the context of epidermal hyperplasia and atrophy. Decreased TWEAK immunoreactivity was regularly observed in common warts, actinic keratosis and Bowen's disease, particularly in areas of marked proliferation as evidenced by PCNA‐positive nuclei. In squamous cell carcinoma, expression of TWEAK ranged from strong to completely absent, and it mostly corresponded with the expression of cytokeratin‐10. TWEAK was absent in keratoacanthoma and basal cell carcinoma.
Conclusions: TWEAK is a constitutively expressed epidermal protein whose downregulation might be an early indicator of disturbed differentiation or pathologic proliferation of keratinocytes that accompany inflammatory and neoplastic skin diseases.
Peternel S, Manestar‐Blažić T, Brajac I, Prpić‐Massari L, Kaštelan M. Expression of TWEAK in normal human skin, dermatitis and epidermal neoplasms: association with proliferation and differentiation of keratinocytes.
TNF-related apoptosis-inducing ligand (TRAIL) is recognized as an important regulator of immune responses during infections and various autoimmune-mediated pathologies. Its role in inflammatory ...dermatoses is largely unknown. We aimed to investigate the expression of TRAIL and its receptors DR4 and DR5 in psoriasis vulgaris. Immunohistochemistry for TRAIL, DR4 and DR5 was performed on samples of lesional (
n
= 10) and non-lesional (
n
= 10) skin of patients with plaque psoriasis and skin of healthy volunteers (
n
= 10). Expression of TRAIL and its receptors was further examined by means of double immunofluorescence staining and co-localization with CD4, CD8, CD11c, CD68, CD16 and CD56 markers. Immunohistochemical staining for TRAIL was significantly enhanced in psoriatic lesional as well as non-lesional epidermis compared to the epidermis of healthy skin. Lesional epidermis also showed increased immunoreactivity for DR5. In addition, expression of TRAIL and both of its receptors was significantly increased in the dermis of lesional skin. As evidenced by double immunofluorescence, TRAIL was readily expressed by most of the examined cells of the inflammatory infiltrate in psoriatic lesions. In contrast, the expression of DR4 was found mostly among CD4+ and CD8+ cells but was only nuclear, while DR5 showed cytoplasmic staining in rare CD16+, CD56+ and CD68+ cells. According to abundant in situ presence of TRAIL and its receptors in lesional psoriatic skin, it seems that this cytokine participates in the complex interplay between keratinocytes and cells of the dermal infiltrate and thus contributes to the inflammatory cycle in psoriasis vulgaris.
This paper presents an exploratory study of the relationship between wine producers and distributors in the Croatian wine sector. It focuses on the impact of distribution channels on the bargaining ...position of wine producers, thereby adding to the growing body of research seeking to determine the factors that influence the growth potential of the traditional agricultural sector. Due to the fragmentation on the production side of the market and a high level of concentration on the distribution side, the wine sector provides a suitable context for studying the bargaining power of agricultural (wine) producers and hypothesizing on future outcomes in terms of industry structure and growth potential. Presuming that the share of value retained by the wine producer depends on his bargaining position, two hypotheses were tested: H1: A higher degree of self-reliance improves a wine producer’s bargaining position and H2: A higher number of distribution channels improves a wine producer’s bargaining position. After a brief review of relevant scientific literature, five regression models were created and tested on a sample of 124 Croatian wine producers, which yielded statistically significant results confirming the hypotheses. the final model controls for production volume, number of labels and respective region. The paper ends with some general conclusions and recommendations for future research.
The paper addresses the issue of strategic misconceptions in creating a national framework for an industry of strategic importance. In this paper, the shipbuilding industry was chosen as a model for ...analysing the strategic adjustments of decision makers in business entities and on national level before EU accession and its consequences on the national economy as a whole. The main hypothesis of the paper is that shipbuilding has a broad extent of externalities in the national economy, and therefore, by leading it properly, especially in times of high unemployment and low level of GDP growth, it can act as an important generator of economic growth. The findings are put into the context of the Croatian government shipbuilding development strategy, EU recommendations for the development of shipbuilding industry and their impact on the financial, organizational and managerial issues in Croatian shipyards.
This study examined the frequency of dermatophytoses in the Primorsko-Goranska County, a north-western part of Croatia, over a period of 21 years (1988-2008). All fungal samples were microscopically ...examined with 20% potassium hydroxide (KOH) solution. Fungal infections were confirmed in 26.9% cases. Out of these, dermatophytes were isolated in 38.3%, Candida spp. infection in 55.1% cases, while non-dermatophyte molds were identified in 6.6% isolates. The most frequently isolated dermatophyte was Trichophyton (T.) mentagrophytes var. interdigitalis (55.4%), followed by Mycrosporum (M.) canis (36.9%), T. violaceum (3.2%), M. gypseum (2.2%), and T. verrucosum (1.3%). Epidermophyton (E.) floccosum (0.9%) and T. rubrum (0.1%) were identified only sporadically. The most common dermatophytosis diagnosed in the 21-year period was tinea pedis (26.2%) followed by tinea capitis (21.8%) and tinea corporis (20.1%). Toenail onychomycosis (14.5%) was more common than fingernail onychomycosis (2.0%). T. mentagrophytes var. interdigitalis was the major pathogen causing tinea pedis (86.6%) as well as toenail onychomycosis (93.9%), while M. canis was most frequently isolated in tinea capitis (98.6%), tinea corporis (62.1%), and tinea faciei (40.2%). With regard to age and sex, T. mentagrophytes var. interdigitalis infections were predominant in middle-aged men. M. canis affected mostly children up to 9 years with a slight predominance in girls. Data from epidemiological trend analysis such as presented in our study are important for evidence-based public health measures for the prevention and control of dermatophytoses.
In this work, a multi-class analytical method for determination of 22 frequently used pharmaceuticals was developed and validated. Analytes were from different classes for example macrolides, ...fluoroquinolones, tetracyclines, sulfonamides, anthelmintics, anesthetics, and others. Method was intended for analysis of aqueous samples so the sample preparation was done using solid-phase extraction (SPE). Different sorbents (C8, C18, polymeric, and ion exchange sorbents) combining different eluents (methanol, ethanol, acetonitrile, acetone, ethyl acetate) were investigated during development of sample preparation step. Samples were analyzed using HPLC-MS/MS, and therefore, chromatographic and mass spectrometer conditions were investigated. Optimal extraction efficiencies for most of the investigated analytes were obtained with Oasis HLB polymeric sorbents with acetonitrile as eluent. A study of matrix effect was carried out for wastewater treatment plant (WWTP) influent and effluent. The method was validated for linearity, detection limits and quantification limits, repeatability, and reproducibility. Method detection limits were in the range of 2.0–204.0 ng L
−1
for WWTP influent except for sulfaguanidine and dexamethasone. Also, method detection limits for WWTP effluent were from 1.0 to 115.4 ng L
−1
. Method was successfully applied for analysis of real wastewater samples from municipal wastewater treatment plant. In the influent, pharmaceuticals from all investigated groups were present and the concentrations were from 50.0 to 4914.3 ng L
−1
for influent and 26.9 to 1699.2 ng L
−1
for effluent. It was also reported that some pharmaceuticals showed higher concentrations in the wastewater effluent than in the influent.
