Comparative effectiveness of tildrakizumab 200 mg versus tildrakizumab 100 mg in psoriatic patients with high disease burden or above 90 kg of body weight: a 16-week multicenter retrospective study - IL PSO (Italian landscape psoriasis)

Purpose: Tildrakizumab is a selective inhibitor of IL-23 approved for the treatment of moderate-to-severe plaque psoriasis in two dosages. We conducted a 16-week multicenter retrospective study to compare the effectiveness and safety of tildrakizumab 200 mg versus tildrakizumab 100 mg in patients with a high disease burden or high body weight. Materials and methods: Our retrospective study included 134 patients treated with tildrakizumab 200 mg and 364 patients treated with tildrakizumab 100 mg from 28 Italian Dermatology Units affected by moderate-to-severe plaque psoriasis. The patients had a body weight above 90 kg or a high disease burden (Psoriasis Area and Severity Index [PASI] ≥ 16 or the involvement of difficult-to-treat areas). We evaluated the effectiveness of tildrakizumab at the week-16 visit in terms of PASI90, PASI100 and absolute PASI ≤ 2. Results: After 16 weeks of treatment with tildrakizumab 200 mg, PASI90 was reached by 57.5% of patients and PASI100 by 39.6% of patients. At the same time point, 34.3% and 24.2% of patients treated with tildrakizumab 100 mg achieved PASI90 and PASI100, respectively. Conclusions: Our data suggest that tildrakizumab 200 mg has better effectiveness than tildrakizumab 100 mg in patients with a body weight ≥ 90 kg and a high disease burden

Evaluation of high-dose daptomycin for therapy of experimental Staphylococcus aureus foreign body infection

BACKGROUND: Daptomycin is a novel cyclic lipopeptide whose bactericidal activity is not affected by current antibiotic resistance mechanisms displayed by S. aureus clinical isolates. This study reports the therapeutic activity of high-dose daptomycin compared to standard regimens of oxacillin and vancomycin in a difficult-to-treat, rat tissue cage model of experimental therapy of chronic S. aureus foreign body infection. METHODS: The methicillin-susceptible S. aureus (MSSA) strain I20 is a clinical isolate from catheter-related sepsis. MICs, MBCs, and time-kill curves of each antibiotic were evaluated as recommended by NCCLS, including supplementation with physiological levels (50 mg/L) of Ca(2+ )for daptomycin. Two weeks after local infection of subcutaneously implanted tissue cages with MSSA I20, each animal received (i.p.) twice-daily doses of daptomycin, oxacillin, or vancomycin for 7 days, or was left untreated. The reductions of CFU counts in each treatment group were analysed by ANOVA and Newman-Keuls multiple comparisons procedures. RESULTS: The MICs and MBCs of daptomycin, oxacillin, or vancomycin for MSSA strain I20 were 0.5 and 1, 0.5 and 1, or 1 and 2 mg/L, respectively. In vitro elimination of strain I20 was more rapid with 8 mg/L of daptomycin compared to oxacillin or vancomycin. Twice-daily administered daptomycin (30 mg/kg), oxacillin (200 mg/kg), or vancomycin (50 mg/kg vancomycin) yielded bactericidal antibiotic levels in infected cage fluids throughout therapy. Before therapy, mean (± SEM) viable counts of strain I20 were 6.68 ± 0.10 log(10 )CFU/mL of cage fluid (n = 74). After 7 days of therapy, the mean (± SEM) reduction in viable counts of MSSA I20 was 2.62 (± 0.30) log(10 )CFU/mL in cages (n = 18) of daptomycin-treated rats, exceeding by >2-fold (P < 0.01) the viable count reductions of 0.92 (± 0.23; n = 19) and 0.96 (± 0.24; n = 18) log(10 )CFU/mL in cages of oxacillin-treated and vancomycin-treated rats, respectively. Viable counts in cage fluids of untreated animals increased by 0.48 (± 0.24; n = 19) log(10 )CFU/mL. CONCLUSION: The improved efficacy of the twice-daily regimen of daptomycin (30 mg/kg) compared to oxacillin (200 mg/kg) or vancomycin (50 mg/kg) may result from optimisation of its pharmacokinetic and bactericidal properties in infected cage fluids

Long-term proactive management of psoriasis with calcipotriol and betamethasone dipropionate foam: an Italian consensus through a combined nominal group technique and Delphi approach

Background: Although long-term management of psoriasis is paramount, this approach is challenging in clinical practice. In the recent PSO-LONG trial, a fixed-dose combination of betamethasone dipropionate (BD) and calcipotriol (Cal) foam applied twice a week on non-consecutive days for 52 weeks (proactive treatment) reduced the risk of relapse. However, the role of Cal/BD foam in the long-term management of psoriasis needs further clarifications. The ProActive Management (PAM) program, a nationwide Italian project, aims at reaching a consensus on the role of proactive management of psoriasis. Methods: A steering committee generated some statements through the nominal group technique (NGT). The statements were voted by an expert panel in an adapted Delphi voting process. Results: Eighteen statements were proposed, and the majority of them (14/18) reached a consensus during the Delphi voting. The need to provide long-term proactive topical treatment to reduce the risk of relapse for the treatment of challenging diseases sites or in patients where phototherapy or systemic therapies are contraindicated/ineffective was widely recognized. A consensus was reached about the possibility to associate the proactive treatment with systemic and biological therapies, without the need for dose intensification, thus favoring a prolonged remission. Moreover, the proactive treatment was recognized as more effective than weekend therapy in increasing time free from relapses. Approaches to improve adherence, on the other hand, need further investigation. Conclusions: The inclusion in guidelines of a proactive strategy among the effective treatment options will be a fundamental step in the evolution of a mild-moderate psoriasis therapeutic approach

Integrazioni nelle dorature degli stucchi di Villa Carrara (GE)

pubblicazione nell'ambito dell'Assegno di ricerca "Tecniche diagnostiche e di intervento nel cantiere di restauro" - settore Icar 19/Restauro aa 2009-201

Analysis of the bias induced by voxel and unstructured mesh Monte Carlo models for the MCNP6 code in orthovoltage applications

The use of Monte Carlo methods for the set up of Treatment Planning Systems (TPS) in radiotherapy applications is a current standard. The most advanced modeling techniques aim at directly link the output of CT scans to a patient-specific model build up instead of standard phantoms and look-up tables. This link represents a critical step since even the most accurate segmentation and organ volume definition must be translated into a suitable input for the Monte Carlo code. During that step, the segmented volume is usually mapped on a regular geometrical lattice (voxels). A more sophisticated option appears to be a volume description based on an Unstructured Mesh (UM) geometry typical of current finite element codes. In this paper, we compared the two approaches analyzing the bias induced by the different choices. Starting from anonymous patient DICOM files coming from a CT scan, suitable segmentation and volume definition have been carried out and voxel and UM-based equivalent models for the Monte Carlo code MCNP6 have been built. Some computational phantoms, covering some significant portion of the human body (head and lower limb), have been used as a benchmark of the dose distribution obtained from X-ray sources commonly used in orthovoltage applications. The specific clinical application has been chosen because, despite being used on a growing number of patients and with multi-Gy doses, treatment planning is still based on poorly characterized dose mapping systems such as look-up tables or low-resolution computational phantoms for MC codes. Also, experimental measurements on phantom slabs irradiated by an X-ray source were carried out preliminarily to validate the simulated radiation source. As shown in the results, the UM computational phantoms (built through the Simpleware SCAN-IP\u2122 tool) can reduce the bias induced by the regularity of the classical cubic voxel geometry, give a more accurate description of volumes and complex surfaces and, thanks to an optimized discretization of the volumes, are also able to reduce the computational work. For the same UM models, various comparisons with different voxel sizes have been produced to investigate the dose distributions and evaluate the voxelization effects. The comparison shows a convergence pattern of the voxel model to the UM one. It has been possible to verify that the most significant bias occurs where the dose gradient is higher, along the beam borders and at tissue interfaces. The simulations showed that the UM can be really effective and reliable to compute the dose distributions within computational anthropomorphic phantoms obtained from the patient\u2019s CT scans