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.

Radiological assessment of the PRF/BMSC efficacy in the treatment of aseptic nonunions: A retrospective study on 90 subjects.

BACKGROUND: Nonunion is a major orthopaedic concern because of treatment difficulty, high costs and devastating effects on the patients' life quality. Therefore, there is interest in the use of bone substitutes and cell-based strategies to augment fracture repair. We aimed to verify if Platelet Rich Fibrin (PRF) added with bone marrow stromal cells (BMSC) was able to improve the reparative process in the aseptic nonunion, and to establish whether it was worthwhile with atrophic nonunion. The primary outcome was radiological union. As secondary endpoint, the healing time was assessed, and the radiological consolidation grade at each follow-up. METHODS: We identified 113 subjects with tibia or femur nonunion and retrospectively created two groups. Group A was constituted by 56 subjects who underwent the standard procedure, i.e. Judet decortication with/out internal fixation devices, and opposite cortical homoplastic stick. In 57 patients, the standard procedure was modified by adding PRF and BMSC carried by homologous lyophilised bone chips (group B). The same surgeon performed all the operations. To our knowledge, no data are reported in the literature about such application. Since a "gold standard" for healing quantification does not exist, a new scoring radiological system was applied, at 1.5, 3, 6, 12 and 24 months after treatment. RESULTS: At the final 24-month follow-up, the radiological union percentage was 94,12 in group B and 95,12% in group A. A decreased healing time was demonstrated in the presence of PRF/BMSC in comparison with the standard procedure. When we compared the radiological scores at each follow-up, we found that the PRF/BMSC combination significantly improved the consolidation grade at 1.5-, 3- and 6-month follow-up in femurs and at 1.5-month follow-up in tibiae. Furthermore, an improved consolidation grade was demonstrated in the atrophic subjects treated with adjuvants compared to atrophic patients treated with the standard procedure at 1.5-month follow-up. CONCLUSIONS: This study supports the concept that the use of PRF/BMSC, during the standard procedure, is effective in shortening nonunion healing time. It could allow an early mobilization of patients, minimizing suffering, and could be an effective tool to reduce the health-care costs resulting from this issue. LEVEL OF EVIDENCE: Therapeutic level III.

Investigating psoriasis awareness among patients in Italy: validation of a questionnaire.

OBJECTIVE: Psoriasis can have a profound impact on quality of life (QoL) and an awareness of the processes of the disease and its treatment is important in coping with symptoms. Patients do not always understand the potential consequences of their disease and the wide range of effective treatment strategies now available. We designed and validated a questionnaire to investigate patient awareness and understanding of psoriasis including pathogenesis, diagnosis, prognosis and treatment. PATIENTS AND METHODS: This was a multicentre, cross-sectional investigation involving 14 psoriasis referral centres in Italy. The focus group technique was used by a panel of experts in psoriasis, to draw-up a list of questions exploring pathogenesis, diagnosis, prognosis, factors influencing clinical course of psoriasis as well as QoL issues and sources of information on their condition. Psychometric properties of the questionnaire were tested on a sample of 240 adult patients with psoriasis (including treatment-naïve and -experienced patients). RESULTS: The mean age of patients was 50.3±14.9 years and 34.2% were female. The median time from diagnosis was 13.7 years (IQR 7.3-23.2). The Cronbach alpha was 0.77 and all items showed higher correlations within their own dimensions than to other dimensions. Each domain of awareness was well represented by a single dimension. Mean overall awareness was 59.7±13.1 on a 100-point scale. CONCLUSIONS: Our questionnaire was valid in assessing patient awareness in five relevant areas of psoriasis, and can be useful in both the clinical setting and research studies to evaluate patients' knowledge of psoriasis better, with the final aim of reducing the burden of this chronic condition.

Remission of psoriatic arthritis after etanercept discontinuation: analysis of patients' clinical characteristics leading to disease relapse.

Psoriatic arthritis is a chronic, inflammatory, disabling arthritis affecting up to 30 percent of psoriatic patients. Recently, it has been demonstrated that tumor necrosis factor alpha (TNF-alpha) plays a pivotal role in inducing and maintaining joint damage and that molecules that block this cytokine are effective in the treatment of psoriatic arthritis. Etanercept is a recombinant fusion protein acting as a competitive inhibitor of TNF-alpha, and numerous clinical trials have demonstrated its efficacy in determining psoriatic arthritis remission. However, specific criteria defining psoriatic arthritis remission have not been delineated and few data describing the length of the remission after etanercept discontinuation are available. The aim of this observational, retrospective study was to assess post-remission efficacy maintenance and relapse characteristics after etanercept interruption in patients with moderate-to-severe peripheral psoriatic arthritis (PsA) and cutaneous involvement.

[New toxicological patterns of nanomaterials, nanostructures and nanoparticles]. / Nuovi aspetti tossicologici dei nanomateriali, nanostrutture e nanoparticelle.

Nanomaterials engineered as nanotubes, quantum-dots, dendrimers or hybrid systems are increasing themselves by an annual mean rate of 4-5%, with rapid spread in various sectors e.g. biomedical. The liposolubility through membranes and the hydrosolubility through active transport do not interfere with nanoparticles below a certain size, which without activation processes and carrier, transport through thanks to capillaries, to intracellular pores (60 - 70 nm) and fissures (4 - 6 nm) in the same membranes. Conversely, in the processes of pinocytosis/endocytosis energy and carrier are required and endocytosis clathrin/caveolae mediated,is respectively for nanoparticles higher or lower than 200 nm. In occupational hazard nanostructures ranging from a few nm up to 100 - 150 nm have the ability to affect several organs through inhalation, intestinal, parental or dermal route of access. New toxicological aspects are associated to the capacity of nanomaterials of being more or less biocompatible or hydrosoluble, of creating bonds with proteins or to determine accumulation in the cells due to an incomplete elimination process.

A rare association of inlet patch with laryngospasm: a report of two children and literature review.

The inlet patch (IP) is an area of heterotopic gastric mucosa in the cervical esophagus commonly seen during upper endoscopy. Although generally asymptomatic IP has been associated with esophageal and supraesophageal symptoms and, though rare, in adult with malignant transformation. We describe two cases of recurrent episodes of laryngospasm associated with IP. In both cases there was a good response to prolonged acid suppression therapy.

Continuous treatment of plaque-type psoriasis with etanercept: an observational long-term experience.

To assess the long-term efficacy and safety profile and the patient-reported outcomes (PRO) in patients with moderate-to-severe plaque-type psoriasis receiving continuous etanercept treatment. An open-label study was conducted to evaluate etanercept as long-term treatment for moderate-to-severe plaque psoriasis. Continuous therapy was administered at a dose of 50 mg subcutaneously twice weekly for 12 weeks followed by a continuous treatment with 50 mg subcutaneously once weekly or 25 mg twice weekly throughout a 96-week study. The primary measure of efficacy was the proportion of patients with PASI 75 at week 24, 48 and 96. Patient-reported outcomes (PRO) were also assessed during the study, at week 24, 48 and 96, including the Dermatology Life Quality Index (DLQI) and the Psoriasis Disability Index (PDI). At baseline, mean PASI score, DLQI and PDI for patients eligible to initiate treatment with etanercept showed significant disease severity, quality-of-life impairment and psoriasis-related disability. At week 96, patients showed statistically significant and meaningful improvements. The continuous etanercept regimen provided a consistent improvement in both clinical disease parameters and PRO measures.

Influence and variation of the body mass index in patients treated with etanercept for plaque-type psoriasis.

A relationship between psoriasis, pro-inflammatory cytokines and obesity has been demonstrated. Tumour necrosis factor-alpha (TNF-alpha), that is involved in the pathogenesis of psoriasis, is commonly over-expressed in obese subjects, and seems to be derived from inflammatory cells and adipocytes. The primary aim of this study is to investigate whether the Body Mass Index (BMI) of patients influences the clinical response to etanercept, a competitive inhibitor of TNF-alpha approved for the treatment of moderate-to-severe plaque-type psoriasis. The secondary aim is to evaluate whether the TNF-alpha inhibition influences the weight and BMI profile of patients. One hundred patients received 50 mg etanercept twice weekly for 12 weeks, followed by 25 mg. At weeks-12 and 24, treatment efficacy and tolerability were evaluated, as well as body weight and BMI. BMI values did not correlate with etanercept efficacy. Mean PASI score variation did not show significant differences among the BMI groups. A statistically significant weight gain and BMI variation were observed in a consistent rate of patients. Patient BMI does not influence psoriasis efficacy parameters. Although the role of anti TNF-alpha molecules on weight regulation need to be confirmed, our study shows that etanercept treatment may induce weight gain and a BMI increase.

Etanercept at different dosages in the treatment of generalized pustular psoriasis: a case series.

BACKGROUND: Generalized pustular psoriasis (GPP) is a severe and disabling variant of psoriasis. The treatment of GPP is challenging, often characterized by side effects or unsatisfactory response. Etanercept is a tumor necrosis factor alpha blocking agent that demonstrated a consistent efficacy in the control of psoriasis. OBJECTIVES: We aimed to evaluate the efficacy and safety profile of etanercept at different dosages in GPP. METHODS: Six patients affected by GPP, unresponsive to conventional treatment, received etanercept subcutaneously at the dosages of 25 and 50 mg biweekly for 48 weeks. RESULTS: Our experience led to the observation that the administration of etanercept 50 mg biweekly is an effective dosage, characterized by good efficacy and rapidity of effect. Patients who were continuously treated at this dosage for 24 weeks presented stable conditions and long-term maintenance until week 48 even after a dose reduction to 25 mg. CONCLUSION: We demonstrated a good and durable efficacy of etanercept in patients affected by GPP.

Treatment of erythrodermic psoriasis with etanercept.

BACKGROUND: Severe variants of psoriasis, such as erythrodermic psoriasis, may be associated with serious morbidity and mortality. Current treatment options for erythrodermic psoriasis are limited, unsatisfactory and potentially associated with organ-specific toxicity. Recently, a new class of agents, targeted biological therapies, has emerged. Etanercept is a recombinant human fusion protein acting as a competitive inhibitor of tumour necrosis factor-alpha. The safety and efficacy of etanercept have been widely demonstrated in psoriatic arthritis and moderate to severe plaque-type psoriasis. OBJECTIVES: To assess the efficacy and tolerability of etanercept in the treatment of erythrodermic psoriasis over a period of 24 weeks. METHODS: Ten patients, eight men and two women, were selected to receive etanercept 25 mg subcutaneously twice weekly. The Psoriasis Area and Severity Index (PASI) score, ranging from 0 to 72, was used to assess the severity of disease. RESULTS: Etanercept was well tolerated and led to a significant reduction in the severity of disease over the period of treatment. After 24 weeks, the mean PASI score decreased from 39.1 (baseline) to 5.1. At week 12, five of 10 (50%) patients achieved an improvement of PASI score from baseline exceeding 75%. At week 24, six of 10 patients (60%) achieved or maintained an improvement of PASI score from baseline exceeding 75% while two patients (20%) maintained an improvement of between 50% and 75%. CONCLUSIONS: In this study, etanercept has been demonstrated to be an effective treatment for erythrodermic psoriasis, providing a safe and convenient alternative to current therapies.

[C-reactive protein and homocysteinemia in patients undergoing on-line hemodiafiltration]. / Proteina C-reattiva e omocisteinemia in emodiafiltrazione on-line.

PURPOSE: In renal disease therapy (RDT) patients, high plasma homocysteine (tHcy) is common and high C-reactive protein(CRP) levels can be observed, attributed to the inflammatory process caused by the dialysis itself. Hyperhomocysteinemia and bioincompatibility are considered independent vascular risk factors. This study evaluated the behavior of these parameters in patients undergoing on-line hemodiafiltration (OL-HDF). METHODS: In 56 patients, HDF was performed using high permeability polyamide membranes, exchanging in the post-dilution mode 16-18 L/session of a reinfusate obtained by the on-line system (triple filtration AK200, Gambro). CRP was measured by an immunological method at the start and the end of the session in patients without comorbidities (group 1, n=30)and with inflammatory diseases (group 2, n=26). In 23 of the 56 patients, tHCY was measured (by high performance liquid chromatography (HPLC)) before and after the mid-week session on different schedule of folinic acid, vitamin B12 and vitamin B6. RESULTS: Pre-dialytic CRP was in the normal range in group 1 patients, whereas it was higher in group 2 patients; dialysis did not induce a significant change in either group. The intradialytic percentage tHcy decrease was approximately 50% regardless of the pre-dialytic value, which was significantly different according to the vitamin supplements administered. CONCLUSIONS: HDF, as performed in this study, demonstrated biocompatibility and efficient Hcy removal; therefore, it can prevent cardiovascular disease (CVD) in patients on regular extracorporeal dialysis.

Angiotensin II activates extracellular signal regulated kinases via protein kinase C and epidermal growth factor receptor in breast cancer cells.

Angiotensin II (Ang II) induces, through AT1, intracellular Ca(2+) increase in both normal and cancerous breast cells in primary culture (Greco et al., 2002 Cell Calcium 2:1-10). We here show that Ang II stimulated, in a dose-dependent manner, the 24 h-proliferation of breast cancer cells in primary culture, induced translocation of protein kinase C (PKC)-alpha, -beta1/2, and delta (but not -epsilon, -eta, -theta, -zeta, and -iota), and phosphorylated extracellular-regulated kinases 1 and 2 (ERK1/2). The proliferative effects of Ang II were blocked by the AT1 antagonist, losartan. Also epidermal growth factor (EGF) had mitogenic effects on serum-starved breast cancer cells since induced cell proliferation after 24 h and phosphorylation of ERK1/2. The Ang II-induced proliferation of breast cancer cells was reduced by (a) Gö6976, an inhibitor of conventional PKC-alpha and -beta1, (b) AG1478, an inhibitor of the tyrosine kinase of the EGF receptor (EGFR), and (c) downregulation of 1,2-diacylglycerol-sensitive PKCs achieved by phorbol 12-myristate 13-acetate (PMA). A complete inhibition of the Ang II-induced cell proliferation was achieved using the inhibitor of the mitogen activated protein kinase kinase (MAPKK or MEK), PD098059, or using Gö6976 together with AG1478. These results indicate that in human primary cultured breast cancer cells AT1 regulates mitogenic signaling pathways by two simultaneous mechanisms, one involving conventional PKCs and the other EGFR transactivation.

[Optimization of extracorporeal dialytic treatment: on-line hemodiafiltration]. / Ottimizzazione del trattamento dialitico extracorporeo: l'emodiafiltrazione on-line.

The study evaluates the potential of high ultrafiltration on-line hemodialfiltration (HDF) as a means of achieving the goals of extracorporeal RDT: the removal of small and medium-sized molecules, vascular stability and biocompatibility. The removal of small molecules was correlated with the UF rate and therefore with reinfusate volume. Medium-sized molecules were only removed from high permeability synthetic membranes in HD, but to a greater extent in HDF because of higher absorption. Vascular stability during the dialytic session is improved by convective processes, as is confirmed by a low prevalence of arterial hypertension in HDF patients. This suggests that HDF facilitates the achievement of dry body weight and therefore an improved correction of hydrosaline retention which is the main cause of hypertension in RDT patients. The biocompatibility of the dialytic system depends on the membrane and the dialysate. Synthetic membranes were shown to be much less toxic than cellulosic membranes and ultrapure dialysate was a useful aid to reduce the risk of inflammatory stimuli. On-line HDF associated the value of low-cost sterile dialysate-reinfu sate with a highly efficient and well tolerated technique.

Thermal inactivation of stationary-phase and salt-adapted Listeria monocytogenes during postprocess pasteurization of surimi-based imitation crab meat.

The heat resistance of Listeria monocytogenes in surimi-based imitation crab meat was examined after growth to stationary phase or adaptation to 15% NaCl. An in-package pasteurization treatment at the cold spot of 71.1 degrees C for 15 s was calculated as adequate to inactivate 5 logs of L. monocytogenes (z-value of 5.8 degrees C). The heat resistance of L. monocytogenes in surimi did not increase after adaptation to salt.

Thermal inactivation of stationary-phase and acid-adapted Escherichia coli O157:H7, Salmonella, and Listeria monocytogenes in fruit juices.

The heat resistance of stationary-phase and acid-adapted Escherichia coli O157:H7, Salmonella enterica (serotypes Typhimurium, Enteritidis, Gaminara, Rubislaw, and Hartford), and Listeria monocytogenes was evaluated in single-strength apple. orange, and white grape juices adjusted to pH 3.9. The heat resistance increased significantly (P < 0.05) after acid adaptation. Salmonella had an overall lower heat resistance than the other pathogens. Acid-adapted E. coli O157:H7 presented the highest heat resistance in all juices at the temperatures tested, with lower z-values than Salmonella and L. monocytogenes. The heat resistance (D(60 degrees C)-values) of all three pathogens, assessed in tryptic soy broth adjusted to different pH values, increased above pH 4.0. From the results obtained in this study, one example of a treatment that will inactivate 5 logs of vegetative pathogens was calculated as 3 s at 71.1 degrees C (z-value of 5.3 degrees C). Normal processing conditions calculated for hot-filled, shelf-stable juices achieve a lethality in excess of 50,000 D for all three pathogens.

Heat resistance of an outbreak strain of Listeria monocytogenes in hot dog batter.

The heat resistance of a strain of Listeria monocytogenes responsible for a listeriosis outbreak in hot dogs was not higher than the heat resistance of other L. monocytogenes strains when tested in tryptic soy broth and in laboratory-prepared hot dog batter. For the thermal death time experiments, the cells were grown to stationary phase or were starved in phosphate-buffered saline, pH 7, for 6 h at 30 degrees C. Starvation increased the heat resistance of L. monocytogenes in broth but not in hot dog batter. D-values in hot dog batter were higher than in broth. For the hot dog formulation used in this study, cooking the hot dog batter for 30 s at 71.1 degrees C (160 degrees F), or its equivalent using a z-value of 6 degrees C (11 degrees F), would inactivate 5 logs of L. monocytogenes.