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

Experimental study of phase correction determination in steel by stacking method experiment

Fil: Beer, E. Instituto Nacional de Tecnología Industrial (INTI); ArgentinaFil: Álvarez, L. Instituto Nacional de Tecnología Industrial (INTI); ArgentinaFil: Bastida, K. Instituto Nacional de Tecnología Industrial (INTI); ArgentinaFil: Giarmana, G. Instituto Nacional de Tecnología Industrial (INTI); ArgentinaFil: Di Lillo, L. Instituto Nacional de Tecnología Industrial (INTI); Argentin

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

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

Psychometric properties of the Spanish version of the Jefferson Scale of Empathy: making sense of the total score through a second order confirmatory factor analysis

Background: Empathy is a key aspect of the physician-patient interactions. The Jefferson Scale of Empathy (JSE) is one of the most used empathy measures of medical students. The development of cross-cultural empathy studies depends on valid and reliable translations of the JSE. This study sought to: (1) adapt and assess the psychometric properties in Spanish students of the Spanish JSE validated in Mexican students; (2) test a second order latent factor model. Methods: The Spanish JSE was adapted from the Spanish JSE-S, resulting in a final version of the measure. A non-probabilistic sample of 1104 medical students of two Spanish medical schools completed a socio-demographic and the Spanish JSE-S. Descriptive statistics, along with a confirmatory factor analysis, the average variance extracted (AVE), Cronbach's alphas and composite reliability (CR) coefficients were computed. An independent samples t-test was performed to access sex differences. Results: The Spanish JSE-S demonstrated acceptable to good sensitivity (individual items - except for item 2 - and JSE-S total score: -2.72 < Sk < 0.35 and -0.77 < Ku < 7.85), convergent validity (AVE: between 0.28 and 0.45) and reliability (Cronbach's alphas: between 0.62 and 0.78; CR: between 0.62 and 0.87). The confirmatory factor analysis supported the three-factor solution and the second order latent factor model. Conclusions: The findings provide support for the sensitivity, construct validity and reliability of the adapted Spanish JSE-S with Spanish medical students. Data confirm the hypothesized second order latent factor model. This version may be useful in future research examining empathy in Spanish medical students, as well as in cross-cultural studies.info:eu-repo/semantics/publishedVersio

Why Are Outcomes Different for Registry Patients Enrolled Prospectively and Retrospectively? Insights from the Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF).

Background: Retrospective and prospective observational studies are designed to reflect real-world evidence on clinical practice, but can yield conflicting results. The GARFIELD-AF Registry includes both methods of enrolment and allows analysis of differences in patient characteristics and outcomes that may result. Methods and Results: Patients with atrial fibrillation (AF) and ≥1 risk factor for stroke at diagnosis of AF were recruited either retrospectively (n = 5069) or prospectively (n = 5501) from 19 countries and then followed prospectively. The retrospectively enrolled cohort comprised patients with established AF (for a least 6, and up to 24 months before enrolment), who were identified retrospectively (and baseline and partial follow-up data were collected from the emedical records) and then followed prospectively between 0-18 months (such that the total time of follow-up was 24 months; data collection Dec-2009 and Oct-2010). In the prospectively enrolled cohort, patients with newly diagnosed AF (≤6 weeks after diagnosis) were recruited between Mar-2010 and Oct-2011 and were followed for 24 months after enrolment. Differences between the cohorts were observed in clinical characteristics, including type of AF, stroke prevention strategies, and event rates. More patients in the retrospectively identified cohort received vitamin K antagonists (62.1% vs. 53.2%) and fewer received non-vitamin K oral anticoagulants (1.8% vs . 4.2%). All-cause mortality rates per 100 person-years during the prospective follow-up (starting the first study visit up to 1 year) were significantly lower in the retrospective than prospectively identified cohort (3.04 [95% CI 2.51 to 3.67] vs . 4.05 [95% CI 3.53 to 4.63]; p = 0.016). Conclusions: Interpretations of data from registries that aim to evaluate the characteristics and outcomes of patients with AF must take account of differences in registry design and the impact of recall bias and survivorship bias that is incurred with retrospective enrolment. Clinical Trial Registration: - URL: http://www.clinicaltrials.gov . Unique identifier for GARFIELD-AF (NCT01090362)

An easier life to come for mosquito researchers. Field-testing across Italy supports Vectrack system for automatic counting, identification and absolute density estimation of Aedes albopictus and Culex pipiens adults

Background: Disease-vector mosquito monitoring is an essential prerequisite to optimize control interventions and evidence-based risk predictions. However, conventional entomological monitoring methods are labor- and time- consuming and do not allow high temporal/spatial resolution. In 2022, a novel system coupling an optical sensor with machine learning technologies (VECTRACK) proved efective in counting and identifying Aedes albopictus and Culex pipiens adult females and males. Here, we carried out the first extensive field evaluation of the VECTRACK system to assess: (i) whether the catching capacity of a commercial G-Mosquitaire trap (BGM) for adult mosquito equipped with VECTRACK (BGM+VECT) was afected by the sensor; (ii) the accuracy of the VECTRACK algorithm in correctly classifying the target mosquito species genus and sex; (iii) Ae. albopictus capture rate of BGM with or without VECTRACK. Methods: The same experimental design was implemented in four areas in northern (Bergamo and Padua districts), central (Rome) and southern (Procida Island, Naples) Italy. In each area, three types of traps—one BGM, one BGM+VECT and the combination of four sticky traps (STs)—were rotated each 48 h in three diferent sites. Each sampling scheme was replicated three times/area. Collected mosquitoes were counted and identifed by both the VECTRACK algorithm and operator-mediated morphological examination. The performance of the VECTRACK system was assessed by generalized linear mixed and linear regression models. Aedes albopictus capture rates of BGMs were calculated based on the known capture rate of ST. Results: A total of 3829 mosquitoes (90.2% Ae. albopictus) were captured in 18 collection-days/trap/site. BGM and BGM+VECT showed a similar performance in collecting target mosquitoes. Results show high correlation between visual and automatic identifcation methods (Spearman Ae. albopictus: females=0.97; males=0.89; P&lt;0.0001) and low count errors. Moreover, the results allowed quantifying the heterogeneous efectiveness associated with diferent trap types in collecting Ae. albopictus and predicting estimates of its absolute density. Conclusions: Obtained results strongly support the VECTRACK system as a powerful tool for mosquito monitoring and research, and its applicability over a range of ecological conditions, accounting for its high potential for continuous monitoring with minimal human effort

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

Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease

Background: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. Methods: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P = 0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P = 0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P = 0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P = 0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P = 0.31). Conclusions: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846.