Upadacitinib effectiveness and factors associated with minimal disease activity achievement in patients with psoriatic arthritis: preliminary data of a real-life multicenter study

Background Upadacitinib (UPA) is a selective JAK inhibitor recently approved for the treatment of psoriatic arthritis (PsA). In this post-approval study, we aimed to evaluate the effectiveness and safety of UPA over 24 weeks and identify clinical predictors of response, in a multicentric cohort of patients affected by PsA.Methods One hundred and twenty-six patients with PsA treated with UPA were enrolled in 10 Italian centres. UPA effectiveness outcomes, such as the proportion of patients with MDA status, DAPSA remission, and low disease activity, ASDAS-CRP inactive and low disease activity, and change from baseline in DAPSA and ASDAS-CRP scores, were evaluated every 12 weeks until week 24. The proportion of DAPSA minor, moderate, and major improvement, and ASDAS clinically important improvement (CII) and major improvement (MI) were considered as well. All treatment-related adverse events were collected during the observation period. Clinical predictors of MDA response at week 24 were evaluated through multivariate analysis.Results At baseline, 124/126 (98%) and 54/126 (43%) patients showed peripheral and axial involvement, respectively; 110 (87%) patients were intolerant or resistant to biologic DMARDs.At 24 weeks, MDA status, DAPSA remission, and ASDAS-CRP inactive disease were achieved in 47%, 23%, and 48% of patients, respectively. Minor, moderate, and major DAPSA improvement was observed in 67%, 39%, and 23%, respectively; while 65% and 35% achieved ASDAS-CRP CII and MI, respectively. The mean change from baseline was 15.9 +/- 13.5 (p < 0.001) for DAPSA and 1.21 +/- 0.97 (p < 0.001) for ASDAS-CRP. thirteen patients (10%) discontinued UPA due to a lack of efficacy or non-serious adverse events. No serious adverse events were observed. Male gender (OR 2.54, 95% CI 1.03-6.25 p = 0.043), being naive to biological DMARDs (OR 4.13, 95% CI 1.34-12.71, p = 0.013) and elevated baseline CRP (OR 2.49, 95% CI 1.02-6.12, p = 0.046) were associated with MDA response at week 24.conclusions this is one of the first real-life studies supporting the effectiveness of UPA and its safety profile in PsA patients. Furthermore, the study identifies predictors of MDA response to UPA treatment at 6 months

Planck 2015 results. XIII. Cosmological parameters

We present results based on full-mission Planck observations of temperature and polarization anisotropies of the CMB. These data are consistent with the six-parameter inflationary LCDM cosmology. From the Planck temperature and lensing data, for this cosmology we find a Hubble constant, H0= (67.8 +/- 0.9) km/s/Mpc, a matter density parameter Omega_m = 0.308 +/- 0.012 and a scalar spectral index with n_s = 0.968 +/- 0.006. (We quote 68% errors on measured parameters and 95% limits on other parameters.) Combined with Planck temperature and lensing data, Planck LFI polarization measurements lead to a reionization optical depth of tau = 0.066 +/- 0.016. Combining Planck with other astrophysical data we find N_ eff = 3.15 +/- 0.23 for the effective number of relativistic degrees of freedom and the sum of neutrino masses is constrained to < 0.23 eV. Spatial curvature is found to be |Omega_K| < 0.005. For LCDM we find a limit on the tensor-to-scalar ratio of r <0.11 consistent with the B-mode constraints from an analysis of BICEP2, Keck Array, and Planck (BKP) data. Adding the BKP data leads to a tighter constraint of r < 0.09. We find no evidence for isocurvature perturbations or cosmic defects. The equation of state of dark energy is constrained to w = -1.006 +/- 0.045. Standard big bang nucleosynthesis predictions for the Planck LCDM cosmology are in excellent agreement with observations. We investigate annihilating dark matter and deviations from standard recombination, finding no evidence for new physics. The Planck results for base LCDM are in agreement with BAO data and with the JLA SNe sample. However the amplitude of the fluctuations is found to be higher than inferred from rich cluster counts and weak gravitational lensing. Apart from these tensions, the base LCDM cosmology provides an excellent description of the Planck CMB observations and many other astrophysical data sets

Planck 2015 results I. Overview of products and scientific results

The European Space Agency's Planck satellite, which is dedicated to studying the early Universe and its subsequent evolution, was launched on 14 May 2009. It scanned the microwave and submillimetre sky continuously between 12 August 2009 and 23 October 2013. In February 2015, ESA and the Planck Collaboration released the second set of cosmology products based on data from the entire Planck mission, including both temperature and polarization, along with a set of scientific and technical papers and a web-based explanatory supplement. This paper gives an overview of the main characteristics of the data and the data products in the release, as well as the associated cosmological and astrophysical science results and papers. The data products include maps of the cosmic microwave background (CMB), the thermal Sunyaev-Zeldovich effect, diffuse foregrounds in temperature and polarization, catalogues of compact Galactic and extragalactic sources (including separate catalogues of Sunyaev-Zeldovich clusters and Galactic cold clumps), and extensive simulations of signals and noise used in assessing uncertainties and the performance of the analysis methods. The likelihood code used to assess cosmological models against the Planck data is described, along with a CMB lensing likelihood. Scientific results include cosmological parameters derived from CMB power spectra, gravitational lensing, and cluster counts, as well as constraints on inflation, non-Gaussianity, primordial magnetic fields, dark energy, and modified gravity, and new results on low-frequency Galactic foregrounds

The ATTRACT study: screening for the early identification of axial psoriatic arthritis in a cohort of Italian psoriatic patients

Objective: There is growing interest in the early identification of patients with axial psoriatic arthritis (axPsA). We aimed to evaluate whether a dermatology-based screening strategy could help to identify axPsA patients. Methods: The dermatologist-centered screening (DCS) questionnaire was administrated by Dermatologists to consecutive patients fulfilling the inclusion criteria (1. age ≥ 18 years and 2. clinical diagnosis of psoriasis made by a dermatologist) to identify patients eligible (affirmative answers 1-3c of the DCS) for rheumatological evaluation. Clinical, laboratory, genetic, and imaging data were collected from all referred patients. Results: Among the 365 patients screened, 265 fulfilled the inclusion criteria and 124/265 (46.8%) were eligible for rheumatological referral. Diagnosis of axPsA, with or without peripheral PsA (pPsA), was made in 36/124 (29.0%) patients; pPsA without axial involvement was found in 21/124 (16.9%) patients. Back pain at screening was recorded in 174 (66%) patients, with 158 (60%) reporting a back pain duration longer than 3 months, and 140 (53%) reporting back pain onset before the age of 45. Active inflammatory and/or structural post-inflammatory changes in the sacroiliac joints and/or spine were observed in all axPsA patients.Patients with PsA showed a numerically longer duration of back pain and higher CRP levels in comparison with patients with Pso without PsA. Conclusion: The DCS tool proved to be a valuable screening strategy for detecting and characterizing patients with axPsA in a real-life cohort of psoriasis patients in a dermatological setting and helped to identify a substantial number of patients affected by undiagnosed pPsA

Additional file 1 of Upadacitinib effectiveness and factors associated with minimal disease activity achievement in patients with psoriatic arthritis: preliminary data of a real-life multicenter study

Additional file 1: Additional Table 1a. Characteristics of the UPREAL-PsA study patients subgroups at baseline. Additional Table 1b. Characteristics of the UPREAL-PsA study patients subgroups at baseline. Additional Table 2. List of the comorbidities considered as Other in patients of the UPREAL-PsA study. Additional Table 3. List of the previous bDMARDs used in bio-failure patients. Additional Table 4. DAPSA responses in patients’ subgroups of the UPREAL-PsA study. Additional Table 5. ASDAS-CRP responses in patients’ subgroups of the UPREAL-PsA study. Additional Table 6. List of all the adverse events observed in patients of the UPREAL-PsA study

Air leak and intraoperative bleeding in thoracic surgery: a Delphi consensus among the members of Italian society of thoracic surgery

BACKGROUND: Persistent air leak and the management of intraoperative blood loss are common threats in thoracic surgical practice. The availability of new procedures, technology and materials is constantly evolving topical hemostats and surgical sealants must be added to this toolkit. Topical hemostats and surgical sealants differ according to their chemical nature and physical characteristics, to their origin and mechanism of action, regulatory/registration and vigilance paths. A Delphi consensus was set to highlight the different points of view on the use of topical haemostatic products and sealants among the members of Italian Society of thoracic surgery. METHODS: The board was formed by a group of five Italian experts; in the first phase after a careful review of the scientific literature and two rounds, the board finally generated 16 consensus statements for testing across a wider audience. During the second phase, the statements were collated into a questionnaire, which was electronically sent to a panel of 46 Italian surgeons, experts in the field. RESULTS: Out of 46 Italian surgeons, 33 (72%) panel members responded to the Delphi questionnaire. All the items reached a positive consensus, with elevated levels of agreement, as demonstrated by the presence of a 100% consensus for nine items. For the remaining 7 statements the minimum level of consent was 88% (29 participants approved the statement and 4 disagreed) and the maximum was 97% (32 participants approved the statement and 1 was in disagreement). CONCLUSIONS: The present Delphi analysis shows that air leak and intraoperative bleeding are clinical problems well known among thoracic surgeons. Nevertheless, the aim of the scientific societies and of the group of experts is to execute the education activities in the surgery community. This Delphi survey suggest the need of wider and updated scientific information about technical and registration characteristics of most recent technologic solutions, such as the of topical hemostats and surgical sealants to provide healthcare and administrative staff with the opportunity to work and interact through a common and shared language and eventually to guarantee minimal requirements of assistance

Multiple Sclerosis in Twins from Continental Italy and Sardinia: A Nationwide Study.

Knowledge about the balance between heritable and nonheritable risk in multiple sclerosis (MS) is based on twin studies in high-prevalence areas. In a study that avoided ascertainment limitations and directly compared continental Italy (medium-prevalence) and Sardinia (high-prevalence), we ascertained 216 pairs from 34,549 patients. This gives a twinning rate of 0.62% among MS patients, significantly less than that of the general population. In continental Italy,probandwise concordance was 14.5% (95% confidence interval, 5.1\u201323.8) for monozygotic and 4.0% (95% confidence interval, 0.8 \u20137.1) for dizygotic twins. Results in Sardinia resemble those in northern populations but in limited numbers. Monozygotic concordance was 22.2% (95% confidence interval, 0\u201349.3) probandwise, but no concordant dizygotic pairs were identified. A questionnaire on 80 items possibly related to disease cause was administered to 70 twin pairs, 135 sporadic patients, and 135 healthy volunteers. Variables positively (7) or negatively (2) associated with predisposition and concordance in twins largely overlapped and were mainly linked to infection. If compared with previous studies, our data demonstrate that penetrance in twins appears to correlate with MS prevalence. They highlight the relevance of nonheritable variables in Mediterranean areas. The apparent underrepresentation of MS among Italian twins draws attention to protective factors, shared by twins, that may influence susceptibility

Planck 2015 results: XI. CMB power spectra, likelihoods, and robustness of parameters

This paper presents the Planck 2015 likelihoods, statistical descriptions of the 2-point correlationfunctions of the cosmic microwave background (CMB) temperature and polarization fluctuations that account for relevant uncertainties, both instrumental and astrophysical in nature. They are based on the same hybrid approach used for the previous release, i.e., a pixel-based likelihood at low multipoles (\ue2\u84\u93 < 30) and a Gaussian approximation to the distribution of cross-power spectra at higher multipoles. The main improvements are the use of more and better processed data and of Planck polarization information, along with more detailed models of foregrounds and instrumental uncertainties. The increased redundancy brought by more than doubling the amount of data analysed enables further consistency checks and enhanced immunity to systematic effects. It also improves the constraining power of Planck, in particular with regard to small-scale foreground properties. Progress in the modelling of foreground emission enables the retention of a larger fraction of the sky to determine the properties of the CMB, which also contributes to the enhanced precision of the spectra. Improvements in data processing and instrumental modelling further reduce uncertainties. Extensive tests establish the robustness and accuracy of the likelihood results, from temperature alone, from polarization alone, and from their combination. For temperature, we also perform a full likelihood analysis of realistic end-to-end simulations of the instrumental response to the sky, which were fed into the actual data processing pipeline; this does not reveal biases from residual low-level instrumental systematics. Even with the increase in precision and robustness, the \uce\u9bCDM cosmological model continues to offer a very good fit to the Planck data. The slope of the primordial scalar fluctuations, ns, is confirmed smaller than unity at more than 5\ucf\u83 from Planck alone. We further validate the robustness of the likelihood results against specific extensions to the baseline cosmology, which are particularly sensitive to data at high multipoles. For instance, the effective number of neutrino species remains compatible with the canonical value of 3.046. For this first detailed analysis of Planck polarization spectra, we concentrate at high multipoles on the E modes, leaving the analysis of the weaker B modes to future work. At low multipoles we use temperature maps at all Planck frequencies along with a subset of polarization data. These data take advantage of Planck's wide frequency coverage to improve the separation of CMB and foreground emission. Within the baseline \uce\u9bCDM cosmology this requires \ucf\u84 = 0.078 \uc2\ub1 0.019 for the reionization optical depth, which is significantly lower than estimates without the use of high-frequency data for explicit monitoring of dust emission. At high multipoles we detect residual systematic errors in E polarization, typically at the \uce\ubcK2level; we therefore choose to retain temperature information alone for high multipoles as the recommended baseline, in particular for testing non-minimal models. Nevertheless, the high-multipole polarization spectra from Planck are already good enough to enable a separate high-precision determination of the parameters of the \uce\u9bCDM model, showing consistency with those established independently from temperature information alone

Planck 2015 results XI. CMB power spectra, likelihoods, and robustness of parameters

This paper presents the Planck 2015 likelihoods, statistical descriptions of the 2-point correlationfunctions of the cosmic microwave background (CMB) temperature and polarization fluctuations that account for relevant uncertainties, both instrumental and astrophysical in nature. They are based on the same hybrid approach used for the previous release, i.e., a pixel-based likelihood at low multipoles (ℓ< 30) and a Gaussian approximation to the distribution of cross-power spectra at higher multipoles. The main improvements are the use of more and better processed data and of Planck polarization information, along with more detailed models of foregrounds and instrumental uncertainties. The increased redundancy brought by more than doubling the amount of data analysed enables further consistency checks and enhanced immunity to systematic effects. It also improves the constraining power of Planck, in particular with regard to small-scale foreground properties. Progress in the modelling of foreground emission enables the retention of a larger fraction of the sky to determine the properties of the CMB, which also contributes to the enhanced precision of the spectra. Improvements in data processing and instrumental modelling further reduce uncertainties. Extensive tests establish the robustness and accuracy of the likelihood results, from temperature alone, from polarization alone, and from their combination. For temperature, we also perform a full likelihood analysis of realistic end-to-end simulations of the instrumental response to the sky, which were fed into the actual data processing pipeline; this does not reveal biases from residual low-level instrumental systematics. Even with the increase in precision and robustness, the ΛCDM cosmological model continues to offer a very good fit to the Planck data. The slope of the primordial scalar fluctuations, ns, is confirmed smaller than unity at more than 5σ from Planck alone. We further validate the robustness of the likelihood results against specific extensions to the baseline cosmology, which are particularly sensitive to data at high multipoles. For instance, the effective number of neutrino species remains compatible with the canonical value of 3.046. For this first detailed analysis of Planck polarization spectra, we concentrate at high multipoles on the E modes, leaving the analysis of the weaker B modes to future work. At low multipoles we use temperature maps at all Planck frequencies along with a subset of polarization data. These data take advantage of Planck’s wide frequency coverage to improve the separation of CMB and foreground emission. Within the baseline ΛCDM cosmology this requires τ = 0.078 ± 0.019 for the reionization optical depth, which is significantly lower than estimates without the use of high-frequency data for explicit monitoring of dust emission. At high multipoles we detect residual systematic errors in E polarization, typically at the μK2 level; we therefore choose to retain temperature information alone for high multipoles as the recommended baseline, in particular for testing non-minimal models. Nevertheless, the high-multipole polarization spectra from Planck are already good enough to enable a separate high-precision determination of the parameters of the ΛCDM model, showing consistency with those established independently from temperature information alone