Effectiveness of cyclosporine A in patients with moderate to severe plaque psoriasis in a real-life clinical setting in Italy: the TRANSITION study.

BACKGROUND: Cyclosporine A (CsA) is one of the systemic therapeutic options for moderate-to-severe psoriasis, based on its efficacy and rapidity of action. The current study investigated the response to CsA in patients with moderate-to-severe plaque psoriasis. MATERIALS AND METHODS: TRANSITION was an observational, cross-sectional, multicentre study which evaluated the proportion of partial- and suboptimal-responders among patients with moderate-to-severe plaque psoriasis treated with continuous CsA for ≥12 weeks. Patients demonstrating a Psoriasis Area and Severity Index (PASI) response of ≥90, ≥75 and <90, ≥50 and <75 and <50 were defined as responders, suboptimal-responders, partial-responders, and non-responders, respectively. RESULTS: A total of 196 patients (mean age, 46.6 years; 62.8% males) from 14 sites in Italy were evaluated. At the study visit, the mean (SD) PASI score was 4.2(5.5) compared with 15.3(7.1) prior to the last CsA cycle. For response categories, 39.8%, 22.4%, 16.8%, and 20.9% of patients were responders, suboptimal-responders, partial-responders, and non-responders to CsA treatment. Overall, 28.6% of patients permanently discontinued treatment with CsA (lack of efficacy [10.2%], poor tolerability and voluntary discontinuation [3.6% each], and other [11.7%]). CONCLUSION: Patients were only partially satisfied with CsA treatment, reporting measurable impact on quality of life. Only 40% patients showed a satisfactory response to CsA.

Real-life experience on effectiveness and safety of dupilumab in adult patients with moderate-to-severe atopic dermatitis.

BACKGROUND: Dupilumab, a fully human monoclonal antibody targeting the alpha subunit of IL-4 was recently approved for the treatment of moderate-to-severe atopic dermatitis (AD) in adult patients. OBJECTIVE: To assess dupilumab effectiveness and safety in adults with moderate-to-severe AD in a real-life Italian multicentre retrospective cohort. METHODS: Adult moderate-to-severe AD patients, referring to 39 Italian centers, received dupilumab in the context of a national patient access program. Disease assessment was performed at baseline, after 4 and 16 weeks of treatment using Eczema-Area-and-Severity-Index (EASI) score, itch and sleep numerical-rating-score (itch-NRS, sleep-NRS) and Dermatology-Life-Quality-Index (DLQI). RESULTS: A total of 109 (71 M/38F) patients was studied. There was a significant reduction in EASI score, itch-NRS, sleep-NRS and DLQI from baseline to week 4 and a further significant decline to week 16. EASI 50, EASI75 and EASI90 were achieved by 59.6%, 28.4% and 9.3% of patients at 4 weeks and by 87.2%, 60.6% and 32.4% of them at 16 weeks, respectively. Adverse events were experienced by 19.2% (21/109) of the patients and they were all mild in intensity, being conjunctivitis the most common side effect. CONCLUSIONS: Dupilumab significantly improved disease severity, pruritus, sleep loss and quality of life with an acceptable safety profile.

Biological therapy downregulates the heterodimer S100A8/A9 (calprotectin) expression in psoriatic patients.

The pathophysiology of psoriasis is very complex and involves an interplay between immune cells and keratinocytes. The keratinocyte production of calprotectin (S100A8/A9), induced by the inflammatory psoriatic milieu, may be involved in initiating immune cell invasion, as well as in propagating inflammation. However, the exact role of calprotectin in psoriasis remains unclear. Therapeutic approaches utilizing adalimumab, etanercept and ustekinumab are widely used in psoriatic treatment, but their anti-inflammatory mechanisms are not fully understood. The aim of this study was to investigate, by immunohistochemical analysis, the expression of the heterocomplex S100A8/A9 in lesional skin from psoriatic patients undergoing biological therapy with adalimumab, etanercept or ustekinumab. Our results showed that S100A8/A9, absent or present at very low level in skin biopsies from healthy subjects, is dramatically upregulated in each epidermal layer from psoriatic patients. Interestingly, calprotectin was mainly localized in keratinocyte nuclei from psoriatic patients, suggesting a role of S100A8/A9 in keratinocyte nuclear function. Furthermore, we have shown that the biological treatment induced a drastic reduction of S100A8/A9 expression in skin biopsies from treated patients, correlating with PASI reduction. Our results suggest that calprotectin may play a crucial role as a significant marker of inflammation in psoriasis, and that its reduction of expression may be considered a favourable prognostic marker in psoriasis.

Eggshell: A green adsorbent for heavy metal removal in an MBR system.

Presence of heavy metals as well as different metal ions in treated wastewater is a problem for the environment as well as human health. This paper aims to investigate the possibility to combine an MBR (membrane biological reactor) with an adsorption process onto powdered eggshell and eggshell membrane in order to improve metal removal from wastewater. The first step of the experimental analysis consists of the evaluation of the compatibility between the two processes. Then, a study about sorbent concentration and size effect on fouling was conducted, because the use of this kind of sorbent could affect membrane performance. The second step of the work concerns the check up of eggshell removal capacity as a function of sorbent size, achieved treating an aqueous solution containing Al(3+), Fe(2+) and Zn(2+) as water pollutants. Finally, synthetic wastewater, containing the metal species, was treated by two alternative process schemes: one of them performs the metal uptake in a dedicated adsorption unit, before the MBR. In the second, the two processes take place in the same unit. Results demonstrate that the optimization of the first option could be a solution to MBR upgrading.

Role of the TNFA -308G > A polymorphism in the genetic susceptibility to acne vulgaris in a Sicilian population.

BACKGROUND: Acne vulgaris is a common and clinically well-characterized skin disease that affects a great proportion of the general population and thus, is a major public health problem. The aim of the present study was to investigate whether TNFA -308 G > A polymorphism might be involved in the pathogenesis of acne in a population from Sicily. METHODS: A total of 74 patients with acne and of 88 healthy control subjects from Catania, Italy were examined in the present study. TNFA -308 G > A polymorphisms using the PCR-RFLP method were determined in DNA extracted from buccal swabs. RESULTS: When controls were compared to acne patients, their genotype distributions, respectively G/G: 64.3%, G/A: 35.7% and G/G: 74.0%, G/A: 26.0%, were shown to be different, although not statistically significant (p = 0.191). A significant protective association between the TNFA -308 GA genotype and acne in males (p = 0.027; OR95% CI: 0.288; 0.094-0.889) was shown. CONCLUSIONS: The present results suggest that TNFA -308 polymorphism may contribute to acne susceptibility, as suggested by the protective effect of the G/A phenotype in the males of the Sicilian cohort. Further studies in larger groups, investigating the TNFA -308G/A or other polymorphisms of this gene in acne patients may be helpful to clarify the pathogenesis of the disease.

Oral supplementation with a nutraceutical containing Echinacea, methionine and antioxidant/immunostimulating compounds in patients with cutaneous viral warts.

AIM: The aim of thos paper was to determine the effect of oral supplementation (OS) with a nutraceutical, containing methionine, Echinacea, zinc, probiotics and other antioxidant and immunostimulating compounds, on the response of cutaneous warts to conventional standard therapy (CST). METHODS: This was an open-label study in adults and adolescents aged 14 years or more and with a body weight ≥40 kg, who had at least one cutaneous viral wart. Eligible patients were consecutively allocated to CST (topical therapy with a preparation containing salicylic acid and lactic acid or liquid nitrogen cryotherapy) alone or CST combined with nutraceutical OS for 4 months. RESULTS: A total of 172 patients were enrolled: 83 received CST alone and 89 CST+OS. During the 6-month observation period, a statistically significant reduction of the mean number of warts was obtained in each treatment group and subgroup. The addition of nutraceutical OS was associated with a significantly lower number of warts at 6 months as compared to CST alone. Complete remission was obtained in 54.5% and 86% of patients in the CST group and CST+OS arm, respectively (P<0.001). The influence of the nutraceutical on the response rate appeared to be more prominent in the subgroup of patients treated with topical therapy. The development of new warts during the study period occurred significantly less frequently with CST+OS compared to CST (9% versus 25%; P=0.004). No adverse events possibly related to the nutraceutical administration were observed. CONCLUSION: Our pilot experience seems to suggest that nutraceutical OS is safe and beneficial in patients with cutaneous warts, and capable of enhancing the response to CST.

[Occult rupture of the spleen in a patient with infectious mononucleosis]. / Rottura splenica "occulta" in paziente con mononucleosi infettiva.

INTRODUCTION: Rupture of the spleen can be secondary to abdominal traumas (usually closed trauma) or spontaneous, can interest an organ normal or with morphological alterations secondary to various pathologies. Among the diseases responsible of occult rupture, infectious diseases are the most frequent and, among these, infectious mononucleosis, that is complicated with splenic rupture in 0.5% of the cases, with 30% of mortality. CASE REPORT: P.M., 16 years old female, admitted with acute abdomen, progressive anaemia and incipient cardiovascular instability, associated with suggestive clinical diagnosis of infectious mononucleosis, confirmed by serological findings and histological examination. Because of the imaging of subcapsular splenic haematoma, probably ruptured and with peritoneal bleeding we opt for emergency laparotomy intraoperative findings allows to splenectomy. DISCUSSION: Splenic rupture in infectious mononucleosis often presents as left hypochondrial pain, rare in uncomplicated cases; its occurrence in a patient with a recent diagnosis of infectious mononucleosis or with clinical or laboratory features suggestive of acute EBV infection, should always be investigated with an urgent abdominal ultrasound scan or CT. This approach is mandatory when hypochondrial pain is associated with pain referred to the left shoulder (Kehr's sign), peritoneal irritation and haemodynamic instability. Patients with splenic rupture in infectious mononucleosis generally undergo emergency splenectomy.