Combination therapy with warfarin plus clopidogrel improves outcomes in femoropopliteal bypass surgery patients

Background: Patients having undergone femoropopliteal bypass surgery remain at significant risk of graft failure. Although antithrombotic therapy is of paramount importance in these patients, the effect of oral anticoagulation therapy (OAT) on outcomes remains unresolved. We performed a randomized, prospective study to assess the impact of OAT plus clopidogrel vs dual antiplatelet therapy on peripheral vascular and systemic cardiovascular outcomes in patients who had undergone femoropopliteal bypass surgery. Methods: Three hundred forty-one patients who had undergone femoropopliteal surgery were enrolled and randomized: 173 patients received clopidogrel 75 mg/d plus OAT with warfarin (C + OAT), and 168 patients received dual antiplatelet therapy with clopidogrel 75 mg/d plus aspirin 100 mg/d (C + acetylsalicylic acid [ASA]). Study end points were graft patency and the occurrence of severe peripheral arterial ischemia, and the incidence of bleeding episodes. Results: Follow-up ranged from 4 to 9 years. The graft patency rate and the freedom from severe peripheral arterial ischemia was significantly higher in C + OAT group than in C + ASA group (P =.026 and.044, respectively, Cox-Mantel test). The linearized incidence of minor bleeding complications was significantly higher in C + OAT group than in C + ASA group (2.85% patient-years vs 1.37% patient-years; P =.03). The incidence of major adverse cardiovascular events, including mortality, was found to be similar (P =.34) for both study groups. Conclusions: In patients who have undergone femoropopliteal vascular surgery, combination therapy with clopidogrel plus warfarin is more effective than dual antiplatelet therapy in increasing graft patency and in reducing severe peripheral ischemia. These improvements are obtained at the expenses of an increase in the rate of minor anticoagulation-related complications. © 2012 Society for Vascular Surgery

RESTITUTIO AD INTEGRUM IN A CASE OF ONJ RELATED TO BEVACIZUMAB

Aim. Bevacizumab is a humanized recombinant monoclonal antibody that blocks vascular endothelial growth factor (VEGF). The activity of VEGF is the ability to promote the vascular endothelial cells proliferation inducing the formation of new blood vessels. Bevacizumab is used in the treatment of selected advanced colon, lung, renal and central nervous system tumours and plays a developing role in the management of breast and ovarian cancers. It is also injected intraocularly for treatment of macular degeneration. Recently, bevacizumab has been reported as responsible of drug-related osteonecrosis of the jaw (ONJ), showing a histological pattern similar to bisphosphonate-related ONJ. Moreover, it may increase the risk for osteonecrosis of the jaw when administered in isolation or when given concurrently with bisphosphonates. Materials and methods. Only few case reports in literature have been reported describing ONJ after bevacizumab administration. In June 2011, a 57-year-old female patient was referred to our department for pain in the left posterior mandibular region. She reported the following anamnestic data: in 2002, for the diagnosis of breast cancer, she underwent to left quadrantectomy and radiant treatment; from October 2010, she was receiving multimodal chemotherapy containing bevacizumab. No previous treatment with bisphosphonates, or other known local and systemic risk factors were reported. Intraoral examination showed a painful area of bone exposure in the left posterior lingual mandible. The surrounding soft tissue was erythematous with purulent discharge and with swelling of the extraoral soft tissue of the left mandible. After interaction with her oncologist, bevacizumab has been suspended and systemic antibiotic (ampicillina/sulbactam intramuscularly twice daily for 8 days and metronidazole 250mg per os twice daily for 8 days), local antiseptics (chlorhexidine 0.2% mouth rinses and 0.5% chlorhexidine gel) were administered. Results. After 15 days, she showed a complete healing after spontaneous sequestration of a necrotic bone fragment. Conclusions. The antiangiogenic and antiresorptive effects of bevacizumab are dose-dependent and time-dependent. Probably this implies that angiogenesis, bone remodelling and healing processes should restart after drug cessation. The present case supports the necessity to apply BRONJ prevention protocol also in patients in therapy with bevacizumab

Use of XR-QA2 radiochromic films for quantitative imaging of a synchrotron radiation beam

This work investigates the use of XR-QA2 radiochromic films for quantitative imaging of a synchrotron radiation (SR) beam. Pieces (200 7 30 mm2) of XR-QA2 film were irradiated in a plane transverse to the beam axis, at the SYRMEP beamline at ELETTRA (Trieste), with a monochromatic beam of size 170 7 3.94 mm2 (H 7 V) and energy of 28, 35, 38 or 40 keV. The response was calibrated in terms of average air kerma (1\uf02d20 mGy), measured with a calibrated ionization chamber. Films were digitized in reflectance mode using a flatbed scanner. The 16-bit red channel was used. The net\uf020reflectance was then converted to photon fluence per unit air kerma (mm-2 mGy-1). The SR beam profile was acquired also with a scintillator (GOS) based, fiberoptic coupled CCD camera as well as with a scintillator based flat panel detector. Horizontal profiles obtained with the two modalities were compared, evaluated in a ROI of 17.71 7 0.59 mm2, across the beam centre. Once corrected for flat field, the CCD profile was scaled in order to have the same average value as the normalized profile acquired with the gafchromic film. The same procedure was followed for the beam images acquired with the flat panel detector. Horizontal and vertical line profiles acquired with the radiochromic film show an uneven 2D distribution of the beam intensity, with variations in the order of 15\uf02d20% in the horizontal direction, while the statistical uncertainties evaluated for the radiochromic dose measurements were 6% at 28 keV. Larger variations up to 64% were observed in the vertical direction. The response of the radiochromic film is comparable to that of the other imaging detectors, within less than 5% variation

Squamous cell carcinoma of the lower lip: FAS/FASL expression, lymphocyte subtypes and outcome.

Squamous cell carcinoma (SCC) of the lip is a relatively common malignancy of the head and neck region. Tumour thickness, grading and perineural invasion are significant prognostic indicators. However, there is still the need of new reliable biological markers able to predict the prognosis of the single cases with an unfavourable biological behaviour unpredictable by the classic clinical-pathological parameters. 32 cases of (SCC) of the lower lip were analysed for their clinicopathologic features, and immunohistochemical expression of Fas/FasL in neoplastic cells and in inflammatory infiltrate. Moreover the density and phenotype of tumour-infiltrating lymphocytes (TIL) were analysed. The results were related with the follow-up of the patients ranging from 2 to 6 years. The cases with over-expression of Fas/FasL in neoplastic cells and Fas+ in T cells preferentially showed a more aggressive clinical behaviour (p<0.01). Moreover we found an alteration of the normal expression of CD4 and CD8 lymphocyte types in ten cases. This data suggest that the Fas/FasL pathway is involved in the close relation between neoplastic cells and T cells and so in the biological behaviour of these tumours

High resolution propagation-based lung imaging at clinically relevant X-ray dose levels

Absorption-based clinical computed tomography (CT) is the current imaging method of choice in the diagnosis of lung diseases. Many pulmonary diseases are affecting microscopic structures of the lung, such as terminal bronchi, alveolar spaces, sublobular blood vessels or the pulmonary interstitial tissue. As spatial resolution in CT is limited by the clinically acceptable applied X-ray dose, a comprehensive diagnosis of conditions such as interstitial lung disease, idiopathic pulmonary fibrosis or the characterization of small pulmonary nodules is limited and may require additional validation by invasive lung biopsies. Propagation-based imaging (PBI) is a phase sensitive X-ray imaging technique capable of reaching high spatial resolutions at relatively low applied radiation dose levels. In this publication, we present technical refinements of PBI for the characterization of different artificial lung pathologies, mimicking clinically relevant patterns in ventilated fresh porcine lungs in a human-scale chest phantom. The combination of a very large propagation distance of 10.7 m and a photon counting detector with [Formula: see text] pixel size enabled high resolution PBI CT with significantly improved dose efficiency, measured by thermoluminescence detectors. Image quality was directly compared with state-of-the-art clinical CT. PBI with increased propagation distance was found to provide improved image quality at the same or even lower X-ray dose levels than clinical CT. By combining PBI with iodine k-edge subtraction imaging we further demonstrate that, the high quality of the calculated iodine concentration maps might be a potential tool for the analysis of lung perfusion in great detail. Our results indicate PBI to be of great value for accurate diagnosis of lung disease in patients as it allows to depict pathological lesions non-invasively at high resolution in 3D. This will especially benefit patients at high risk of complications from invasive lung biopsies such as in the setting of suspected idiopathic pulmonary fibrosis (IPF)

The Italian data on SARS-CoV-2 infection in transplanted patients support an organ specific immune response in liver recipients

Introduction: The study of immune response to SARSCoV-2 infection in different solid organ transplant settings represents an opportunity for clarifying the interplay between SARS-CoV-2 and the immune system. In our nationwide registry study from Italy, we specifically evaluated, during the first wave pandemic, i.e., in non-vaccinated patients, COVID-19 prevalence of infection, mortality, and lethality in liver transplant recipients (LTRs), using non-liver solid transplant recipients (NL-SOTRs) and the Italian general population (GP) as comparators. Methods: Case collection started from February 21 to June 22, 2020, using the data from the National Institute of Health and National Transplant Center, whereas the data analysis was performed on September 30, 2020.To compare the sex- and age-adjusted distribution of infection, mortality, and lethality in LTRs, NL-SOTRs, and Italian GP we applied an indirect standardization method to determine the standardized rate. Results: Among the 43,983 Italian SOTRs with a functioning graft, LTRs accounted for 14,168 patients, of whom 89 were SARS-CoV-2 infected. In the 29,815 NL-SOTRs, 361 cases of SARS-CoV-2 infection were observed. The geographical distribution of the disease was highly variable across the different Italian regions. The standardized rate of infection, mortality, and lethality rates in LTRs resulted lower compared to NL-SOTRs [1.02 (95%CI 0.81-1.23) vs. 2.01 (95%CI 1.8-2.2); 1.0 (95%CI 0.5-1.5) vs. 4.5 (95%CI 3.6-5.3); 1.6 (95%CI 0.7-2.4) vs. 2.8 (95%CI 2.2-3.3), respectively] and comparable to the Italian GP. Discussion: According to the most recent studies on SOTRs and SARS-CoV-2 infection, our data strongly suggest that, in contrast to what was observed in NL-SOTRs receiving a similar immunosuppressive therapy, LTRs have the same risk of SARS-CoV-2 infection, mortality, and lethality observed in the general population. These results suggest an immune response to SARS-CoV-2 infection in LTRS that is different from NL-SOTRs, probably related to the ability of the grafted liver to induce immunotolerance

Electrocardiogram analysis in Anderson-Fabry disease: a valuable tool for progressive phenotypic expression tracking

BackgroundElectrocardiogram (ECG) has proven to be useful for early detection of cardiac involvement in Anderson-Fabry disease (AFD); however, little evidence is available on the association between ECG alterations and the progression of the disease.Aim and MethodsTo perform a cross sectional comparison of ECG abnormalities throughout different left ventricular hypertrophy (LVH) severity subgroups, providing ECG patterns specific of the progressive AFD stages. 189 AFD patients from a multicenter cohort underwent comprehensive ECG analysis, echocardiography, and clinical evaluation.ResultsThe study cohort (39% males, median age 47 years, 68% classical AFD) was divided into 4 groups according to different degree of left ventricular (LV) thickness: group A &amp; LE; 9 mm (n = 52, 28%); group B 10-14 mm (n = 76, 40%); group C 15-19 mm (n = 46, 24%); group D &amp; GE; 20 mm (n = 15, 8%). The most frequent conduction delay was right bundle branch block (RBBB), incomplete in groups B and C (20%,22%) and complete RBBB in group D (54%, p &lt; 0.001); none of the patients had left bundle branch block (LBBB). Left anterior fascicular block, LVH criteria, negative T waves, ST depression were more common in the advanced stages of the disease (p &lt; 0.001). Summarizing our results, we suggested ECG patterns representative of the different AFD stages as assessed by the increases in LV thickness over time (Central Figure). Patients from group A showed mostly a normal ECG (77%) or minor anomalies like LVH criteria (8%) and delta wave/slurred QR onset + borderline PR (8%). Differently, patients from groups B and C exhibited more heterogeneous ECG patterns: LVH (17%; 7% respectively); LVH + LV strain (9%; 17%); incomplete RBBB + repolarization abnormalities (8%; 9%), more frequently associated with LVH criteria in group C than B (8%; 15%). Finally, patients from group D showed very peculiar ECG patterns, represented by complete RBBB + LVH and repolarization abnormalities (40%), sometimes associated with QRS fragmentation (13%).ConclusionsECG is a sensitive tool for early identification and long-term monitoring of cardiac involvement in patients with AFD, providing "instantaneous pictures" along the natural history of AFD. Whether ECG changes may be associated with clinical events remains to be determined

Height and timing of growth spurt during puberty in young people living with vertically acquired HIV in Europe and Thailand.

OBJECTIVE: The aim of this study was to describe growth during puberty in young people with vertically acquired HIV. DESIGN: Pooled data from 12 paediatric HIV cohorts in Europe and Thailand. METHODS: One thousand and ninety-four children initiating a nonnucleoside reverse transcriptase inhibitor or boosted protease inhibitor based regimen aged 1-10 years were included. Super Imposition by Translation And Rotation (SITAR) models described growth from age 8 years using three parameters (average height, timing and shape of the growth spurt), dependent on age and height-for-age z-score (HAZ) (WHO references) at antiretroviral therapy (ART) initiation. Multivariate regression explored characteristics associated with these three parameters. RESULTS: At ART initiation, median age and HAZ was 6.4 [interquartile range (IQR): 2.8, 9.0] years and -1.2 (IQR: -2.3 to -0.2), respectively. Median follow-up was 9.1 (IQR: 6.9, 11.4) years. In girls, older age and lower HAZ at ART initiation were independently associated with a growth spurt which occurred 0.41 (95% confidence interval 0.20-0.62) years later in children starting ART age 6 to 10 years compared with 1 to 2 years and 1.50 (1.21-1.78) years later in those starting with HAZ less than -3 compared with HAZ at least -1. Later growth spurts in girls resulted in continued height growth into later adolescence. In boys starting ART with HAZ less than -1, growth spurts were later in children starting ART in the oldest age group, but for HAZ at least -1, there was no association with age. Girls and boys who initiated ART with HAZ at least -1 maintained a similar height to the WHO reference mean. CONCLUSION: Stunting at ART initiation was associated with later growth spurts in girls. Children with HAZ at least -1 at ART initiation grew in height at the level expected in HIV negative children of a comparable age

Into the storm: diving into the winds of the ultra-hot Jupiter WASP-76 b with HARPS and ESPRESSO

Despite swift progress in the characterisation of exoplanet atmospheres in composition and structure, the study of atmospheric dynamics has not progressed at the same speed. While theoretical models have been developed to describe the lower layers of the atmosphere and, disconnected, the exosphere, little is known about the intermediate layers up to the thermosphere. We aim to provide a clearer picture of atmospheric dynamics for the class of ultra hot Jupiters, highly-irradiated gas giants, on the example of WASP-76~b. We analysed two datasets jointly, obtained with the HARPS and ESPRESSO spectrographs, to interpret the resolved planetary sodium doublet. We then applied an updated version of the MERC code, with added planetary rotation, also provides the possibility to model the latitude dependence of the wind patterns. We retrieve the highest Bayesian evidence for an isothermal atmosphere, interpreted as a mean temperature of 3389±227 K, a uniform day-to-night side wind of 5.5+1.4−2.0 km/s in the lower atmosphere with a vertical wind in the upper atmosphere of 22.7+4.9−4.1 km/s, switching atmospheric wind patterns at 10−3 bar above the reference surface pressure (10 bar). Our results for WASP-76~b are compatible with previous studies of the lower atmospheric dynamics of WASP-76~b and other ultra hot Jupiters. They highlight the need for vertical winds in the intermediate atmosphere above the layers probed by global circulation model studies to explain the line broadening of the sodium doublet in this planet. This work demonstrates the capability of exploiting the resolved spectral line shapes to observationally constrain possible wind patterns in exoplanet atmospheres, an invaluable input to more sophisticated 3D atmospheric models in the future

Two super-Earths at the edge of the habitable zone of the nearby M dwarf TOI-2095

The main scientific goal of TESS is to find planets smaller than Neptune around stars bright enough to allow further characterization studies. Given our current instrumentation and detection biases, M dwarfs are prime targets to search for small planets that are in (or nearby) the habitable zone of their host star. Here we use photometric observations and CARMENES radial velocity measurements to validate a pair of transiting planet candidates found by TESS. The data was fitted simultaneously using a Bayesian MCMC procedure taking into account the stellar variability present in the photometric and spectroscopic time series. We confirm the planetary origin of the two transiting candidates orbiting around TOI-2095 (TIC 235678745). The star is a nearby M dwarf ($d = 41.90 \pm 0.03$ pc, $T_{\rm eff} = 3759 \pm 87$ K, $V = 12.6$ mag) with a stellar mass and radius of $M_\star = 0.44 \pm 0.02 \; M_\odot$ and $R_\star = 0.44 \pm 0.02 \; R_\odot$, respectively. The planetary system is composed of two transiting planets: TOI-2095b with an orbital period of $P_b = 17.66484 \pm (7\times 10^{-5})$ days and TOI-2095c with $P_c = 28.17232 \pm (14\times 10^{-5})$ days. Both planets have similar sizes with $R_b = 1.25 \pm 0.07 \; R_\oplus$ and $R_c = 1.33 \pm 0.08 \; R_\oplus$ for planet b and c, respectively. We put upper limits on the masses of these objects with $M_b < 4.1 \; M_\oplus$ for the inner and $M_c < 7.4 \; M_\oplus$ for the outer planet (95\% confidence level). These two planets present equilibrium temperatures in the range of 300 - 350 K and are close to the inner edge of the habitable zone of their star.Comment: Submitted to Astronomy & Astrophysic