500.05 Comparison Between Fractional Flow Reserve (FFR) vs. Computational Fractional Flow Reserve Derived from Three-dimensional Intravascular Ultrasound (IVUSFR) and Quantitative Flow Ratio (QFR)

BACKGROUND The determination of the ischemic status of a coronary artery by wireless physiologic assessment derived from angiography has been validated and approved in the US. However, the use ofplain angiography quantitative variables does not add much to thephysiology data since it has low correlation with fractional flowreserve (FFR) and predicts clinical outcomes poorly. Recently, a grayscale intravascular ultrasound (IVUS) derived physiology method(IVUSFR) was developed and showed a good correlation with invasiveFFR by combining the geometric advantages of IVUS with physiology.The aim of this study is to assess the coefficient of correlation (R) ofinvasive FFR compared to IVUSFR and quantitative flow ratio (QFR).METHODS Stable coronary artery disease (CAD) patients with intermediate lesions (i.e. 40?80% of diameter stenosis) were assessed by angiography and IVUS. QFR was derived from the angiography images, andIVUSFR was derived from quantitative IVUS data using computationalfluid dynamics. Coefficient of correlation (R) was used in this report.RESULTS Twenty-four patients with 34 lesions were included in theanalysis. The IVUSFR, invasive FFR, Vessel QFR fixed flow (vQFRf),and Vessel QFR contrast flow (vQFRc) values varied from 0.52 to 1.00,0.71 to 0.99, 0.55 to 1.00, and 0.34 to 1.00, respectively. The coefficient of correlation (R) of FFR vs. IVUSFR was 0.79; FFR vs. vQFRf was0.72; FFR vs. vQFRc was 0.65 (Figure).CONCLUSION Compared to invasive FFR, IVUSFR and vQFRf showed asimilar coefficient of correlation and were better than vQFR contrast flowFil: Kajita, Alexandre. Medstart; Estados UnidosFil: Bezerra, Cristiano Guedes. Universidade Federal da Bahia; BrasilFil: Ozaki, Yuichi. Medstart; Estados UnidosFil: Dan, Kazuhiro. Medstart; Estados UnidosFil: Melaku, Gebremedhin D.. Medstart; Estados UnidosFil: Pinton, Fabio A.. Universidade de Sao Paulo; BrasilFil: Falcão, Breno A. A.. Hospital of Messejana; BrasilFil: Mariani, José. Universidade de Sao Paulo; BrasilFil: Bulant, Carlos Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. National Laboratory For Scientific Computing; BrasilFil: Maso Talou, Gonzalo Daniel. National Laboratory For Scientific Computing; BrasilFil: Esteves, Antonio. Universidade de Sao Paulo; BrasilFil: Blanco, Pablo Javier. National Laboratory For Scientific Computing; BrasilFil: Waksman, Ron. Medstart; Estados UnidosFil: Garcia Garcia, Hector M.. Medstart; Estados UnidosFil: Lemons, Pedro Alves. Universidade de Sao Paulo; Brasi

Histopathological study of perilesional skin in patients diagnosed with nonmelanoma skin cancer

Epidemiological and clinical data suggest that actinic damage to the skin is an important predictor of skin carcinogenesis

The effectiveness of Robot-Assisted Gait Training versus conventional therapy on mobility in severely disabled progressIve MultiplE sclerosis patients (RAGTIME): Study protocol for a randomized controlled trial

Background: Gait and mobility impairments affect the quality of life (QoL) of patients with progressive multiple sclerosis (MS). Robot-assisted gait training (RAGT) is an effective rehabilitative treatment but evidence of its superiority compared to other options is lacking. Furthermore, the response to rehabilitation is multidimensional, person-specific and possibly involves functional reorganization processes. The aims of this study are: (1) to test the effectiveness on gait speed, mobility, balance, fatigue and QoL of RAGT compared to conventional therapy (CT) in progressive MS and (2) to explore changes of clinical and circulating biomarkers of neural plasticity. Methods: This will be a parallel-group, randomized controlled trial design with the assessor blinded to the group allocation of participants. Ninety-eight (49 per arm) progressive MS patients (EDSS scale 6-7) will be randomly assigned to receive twelve 2-h training sessions over a 4-week period (three sessions/week) of either: (1) RAGT intervention on a robotic-driven gait orthosis (Lokomat, Hocoma, Switzerland). The training parameters (torque of the knee and hip drives, treadmill speed, body weight support) are set during the first session and progressively adjusted during training progression or (2) individual conventional physiotherapy focusing on over-ground walking training performed with the habitual walking device. The same assessors will perform outcome measurements at four time points: baseline (before the first intervention session); intermediate (after six training sessions); end of treatment (after the completion of 12 sessions); and follow-up (after 3 months from the end of the training program). The primary outcome is gait speed, assessed by the Timed 25-Foot Walk Test. We will also assess walking endurance, balance, depression, fatigue and QoL as well as instrumental laboratory markers (muscle metabolism, cerebral venous hemodynamics, cortical activation) and circulating laboratory markers (rare circulating cell populations pro and anti-inflammatory cytokines/chemokines, growth factors, neurotrophic factors, coagulation factors, other plasma proteins suggested by transcriptomic analysis and metabolic parameters). Discussion: The RAGT training is expected to improve mobility compared to the active control intervention in progressive MS. Unique to this study is the analysis of various potential markers of plasticity in relation with clinical outcomes. Trial registration: ClinicalTrials.gov, identifier: NCT02421731. Registered on 19 January 2015 (retrospectively registered)

Efficacy of cyclosporine a as monotherapy in patients with psoriatic arthritis: A subgroup analysis of the SYNERGY Study

BACKGRO UND: The SYNER GY Study is an observational, multicenter Italian study, conducted in patients with diagnosis of psoriatic arthritis (PsA) treated from at least 3 months with cyclosporine and aimed at assessing patients' seropositivity for viral infections and efficacy and safety of cyclosporine, administered as monotherapy or in combination with other systemic drugs in the routine clinical practice. The aim of this subanalysis of the SYNER GY study was to evaluate the effects of CsA as monotherapy only in PsA over 12 months of observation. MET HOD S: Psoriasis was evaluated by Body Surface Area and the Psoriasis Area Severity Index (PASI). PsA was evaluated by number of swollen and tender joints, painful entheses and fingers with dactylitis, the Bath Ankylosing Spondylitis Activity Index (BASDAI) and by patients' and physicians' global assessment on a 10-point Visual Analogue Scale. RE SULTLTS: Cyclosporine in monotherapy was effective in reducing all the measured disease parameters. The major indexes of cutaneous and spinal involvement, PASI and BASDAI were significantly reduced over the study period, as were the number of swollen and tender peripheral joints, and enthesitis and dactylitis. CONCLUSIONS: Cyclosporine in monotherapy confirmed its efficacy in cutaneous psoriasis and suggested to be effective also on PsA, reducing spinal and peripheral joints' signs and symptoms

Tumour-infiltrating Gr-1+ myeloid cells antagonize senescence in cancer.

Aberrant activation of oncogenes or loss of tumour suppressor genes opposes malignant transformation by triggering a stable arrest in cell growth, which is termed cellular senescence. This process is finely tuned by both cell-autonomous and non-cell-autonomous mechanisms that regulate the entry of tumour cells to senescence. Whether tumour-infiltrating immune cells can oppose senescence is unknown. Here we show that at the onset of senescence, PTEN null prostate tumours in mice are massively infiltrated by a population of CD11b(+)Gr-1(+) myeloid cells that protect a fraction of proliferating tumour cells from senescence, thus sustaining tumour growth. Mechanistically, we found that Gr-1(+) cells antagonize senescence in a paracrine manner by interfering with the senescence-associated secretory phenotype of the tumour through the secretion of interleukin-1 receptor antagonist (IL-1RA). Strikingly, Pten-loss-induced cellular senescence was enhanced in vivo when Il1ra knockout myeloid cells were adoptively transferred to PTEN null mice. Therapeutically, docetaxel-induced senescence and efficacy were higher in PTEN null tumours when the percentage of tumour-infiltrating CD11b(+)Gr-1(+) myeloid cells was reduced using an antagonist of CXC chemokine receptor 2 (CXCR2). Taken together, our findings identify a novel non-cell-autonomous network, established by innate immunity, that controls senescence evasion and chemoresistance. Targeting this network provides novel opportunities for cancer therapy

Paleomagnetism of Holocene lava flows from the Reykjanes Peninsula and the Tungnaá lava sequence (Iceland): implications for flow correlation and ages

The impact of Holocene eruptive events from hot spots like Iceland may have had significant global implications; thus, dating and knowledge of past eruptions chronology is important. However, at high-latitude volcanic islands, the paucity of soils severely limits14C dating, while the poor K content of basalts strongly restricts the use of K/Ar and Ar/Ar methods. Even tephrochronology, based on14C age determinations, refers to layers that rarely lie directly above lava flows to be dated. We report on the paleomagnetic dating of 25 sites from the Reykjanes Peninsula and the Tungnaá lava sequence of Iceland. The gathered paleomagnetic directions were compared with the available reference paleosecular variation curves of the Earth magnetic field to obtain the possible emplacement age intervals. To test the methodâ\u80\u99s validity, we sampled the precisely dated Laki (1783â\u80\u931784 AD) and Eldgjà (934â\u80\u93938 AD) lavas. The age windows obtained for these events encompass the true flow ages. For sites from the Reykjanes peninsula and the Tugnaá lava sequence, we derived multiple possible eruption events and ages. In the Reykjanes peninsula, we propose an older emplacement age (immediately following the 870 AD Iceland Settlement age) for Ogmundarhraun and Kapelluhraun lava fields. For pre-historical (older than the settlement age) Tugnaá eruptions, the method has a dating precision of 300â\u80\u93400 years which allows an increase of the detail in the chronostratigraphy and distribution of lavas in the Tugnaá sequence