Contralateral prophylactic mastectomies. Correlations between primary tumor and histological findings of controlateral breast

Backgound: In Italy in 2015 48,000 new cases of breast carcinomas were diagnosed. Women who are diagnosed with breast cancer have a significant risk of developing contralateral breast cancer during the rest of their lives and this risk is closely associated to the family history, to the onset of breast cancer at a young age and is expressed at about 0.5 to 1% of metachronous tumors per year. The purpose of this work was to evaluate which and how many neoplastic lesions were seen in the contralateral breast that underwent prophylactic mastectomy and to understand what factors predict the appearance of such lesions. Methods: 168 bilateral mastectomies were analyzed in patients with an average age of 47 years, carried out from July 2008 to April 2016, at the Breast Unit of the Sant’Andrea Hospital. We considered women of any age suffering from unilateral breast cancer without either clinical or radiological evidence of a malignant lesion in the contralateral breast and negative for mutations of the BRCA1-BRCA2 genes test. Of the 168 bilateral mastectomies 35 patients were excluded from the study because they underwent neoadjuvant chemotherapy, another 35 patients because they were suffering from a bilateral neoplasia and 7 cases because they had mutated BRCA1 or BRCA2 genes. Therefore the remaining 91 patients were included in the study. Results: Both the histological features of the primary tumor and any lesions found in the contralateral prophylactic breast were analyzed. Histological examination of the main breast showed 59 cases of Invasive Ductal Carcinoma (IDC), 17 cases of Invasive Lobular Carcinoma (ILC), 9 cases of In Situ Ductal Carcinoma (ISDC), 3 microinvasive ductal, 1 invasive tubular carcinoma, 1 in situ lobular and 1 widespread in situ. In the contralateral breast, the definitive histological examination revealed that 47 patients had an occult lesion in the prophylactic contralateral breast; in particular 2 cases of LIN 1, 7 cases of LIN2, 6 cases of lobular carcinoma in situ, 26 between DIN1A/DIN1A-B/DIN1B, 4 cases of carcinoma in situ and 2 cases of Invasive Ductal Carcinoma. The correlation obtained from the observation of the main tumor has shown that in a total of 59 invasive ductal carcinoma 32 have a controlateral occult lesions and in a total of 17 cases of invasive lobular carcinoma 9 have an occult lesion in the prophylactic breast. Of these lesions, the multicentric relationship is that 50% of invasive ductal and invasive lobular carcinoma of the main breast have a contralateral lesion. Conclusion: In conclusion we would like to remind, as demonstrated by our follow-up data and as the literature reiterates, that this surgery does not improve patient survival. Certainly patients with unilateral breast cancer have many surgical therapies to be able to deal with not only having a bilateral mastectomy. The end point of this work is try to understand the risk factors of having a contralateral breast lesion to reduce the probability of a metachronous cance

Rapid detection of copy number variations and point mutations in BRCA1/2 genes using a single workflow by ion semiconductor sequencing pipeline

Molecular analysis of BRCA1 (MIM# 604370) and BRCA2 (MIM #600185) genes is essential for familial breast and ovarian cancer prevention and treatment. An efficient, rapid, cost-effective accurate strategy for the detection of pathogenic variants is crucial. Mutations detection of BRCA1/2 genes includes screening for single nucleotide variants (SNVs), small insertions or deletions (indels), and Copy Number Variations (CNVs). Sanger sequencing is unable to identify CNVs and therefore Multiplex Ligation Probe amplification (MLPA) or Multiplex Amplicon Quantification (MAQ) is used to complete the BRCA1/2 genes analysis. The rapid evolution of Next Generation Sequencing (NGS) technologies allows the search for point mutations and CNVs with a single platform and workflow. In this study we test the possibilities of NGS technology to simultaneously detect point mutations and CNVs in BRCA1/2 genes, using the OncomineTM BRCA Research Assay on Personal Genome Machine (PGM) Platform with Ion Reporter Software for sequencing data analysis (Thermo Fisher Scientific). Comparison between the NGS-CNVs, MLPA and MAQ results shows how the NGS approach is the most complete and fast method for the simultaneous detection of all BRCA mutations, avoiding the usual time consuming multistep approach in the routine diagnostic testing of hereditary breast and ovarian cancers

Potential for non-destructive astrochemistry using the ExoMars PanCam

We investigate the utility of adding a 365 nm ultraviolet (UV) light source to the ExoMars panoramic camera (PanCam) scheduled for launch in 2013. The modification makes it feasible to monitor rover drill cuttings for aromatic organic molecules and provide constraints on polycyclic aromatic hydrocarbons (PAH) as a function of depth to the 2-meter limit of the ExoMars drill. This non-destructive triage allows prioritized deployment of organic detection experiments requiring sample destruction and/or expenditure of non-replaceable resources. Utilizing the Beagle 2 PanCam backup filter wheel fitted with original blue (440 nm), green ( 530 nm), and red ( 670 nm) filters we captured fluorescent images following 365 nm excitation of 3-, 4- and 5-ring PAH species doped on Mars analog peridotite grains. We demonstrate a detection limit for pyrene of 1.5 mu g in granular peridotite doped at pyrene levels of 50 +/- 5 ppm for camera-to-target distance of 1 meter

2015 Update on Acute Adverse Reactions to Gadolinium based Contrast Agents in Cardiovascular MR. Large Multi-National and Multi-Ethnical Population Experience With 37788 Patients From the EuroCMR Registry

Objectives: Specifically we aim to demonstrate that the results of our earlier safety data hold true in this much larger multi-national and multi-ethnical population. Background: We sought to re-evaluate the frequency, manifestations, and severity of acute adverse reactions associated with administration of several gadolinium- based contrast agents during routine CMR on a European level. Methods: Multi-centre, multi-national, and multi-ethnical registry with consecutive enrolment of patients in 57 European centres. Results: During the current observation 37788 doses of Gadolinium based contrast agent were administered to 37788 patients. The mean dose was 24.7 ml (range 5–80 ml), which is equivalent to 0.123 mmol/kg (range 0.01 - 0.3 mmol/kg). Forty-five acute adverse reactions due to contrast administration occurred (0.12 %). Most reactions were classified as mild (43 of 45) according to the American College of Radiology definition. The most frequent complaints following contrast administration were rashes and hives (15 of 45), followed by nausea (10 of 45) and flushes (10 of 45). The event rate ranged from 0.05 % (linear non-ionic agent gadodiamide) to 0.42 % (linear ionic agent gadobenate dimeglumine). Interestingly, we also found different event rates between the three main indications for CMR ranging from 0.05 % (risk stratification in suspected CAD) to 0.22 % (viability in known CAD). Conclusions: The current data indicate that the results of the earlier safety data hold true in this much larger multi-national and multi-ethnical population. Thus, the “off-label” use of Gadolinium based contrast in cardiovascular MR should be regarded as safe concerning the frequency, manifestation and severity of acute events

Sleep and cardiometabolic comorbidities in the obstructive sleep apnoea-COPD overlap syndrome: data from the European Sleep Apnoea Database

Aim The impact of obstructive sleep apnoea (OSA)-COPD overlap syndrome (OVS) on sleep quality and cardiovascular outcomes has not been fully explored. We aimed to compare clinical and polysomnographic characteristics of patients with OVS versus patients with OSA, and to explore pathophysiological links between OVS and comorbidities. Study design and methods This cross-sectional analysis initially included data from 5600 patients with OSA and lung function in the European Sleep Apnoea Database. Two subgroups of patients with OSA (n=1018) or OVS (n=509) were matched (2:1) based on sex, age, body mass index and apnoea-hypopnea index at baseline. Results After matching, patients with OVS had more severe hypoxia, lower sleep efficiency and presented with higher prevalences of arterial hypertension, ischaemic heart disease and heart failure compared with patients with OSA. OVS was associated with a significant decrease in sleep efficiency (mean difference (beta) -3.0%, 95% CI -4.7 to -1.3) and in nocturnal mean peripheral oxyhaemoglobin saturation (S-pO2) (beta -1.1%, 95% CI -1.5 to -0.7). Further analysis revealed that a decrease in forced expiratory volume in 1 s and arterial oxygen tension was related to a decrease in sleep efficiency and in mean nocturnal S-pO2. A COPD diagnosis increased the odds of having heart failure by 1.75 (95% CI 1.15-2.67) and systemic hypertension by 1.36 (95% CI 1.07-1.73). Nocturnal hypoxia was strongly associated with comorbidities; the mean nocturnal S-pO2 and T90 (increase in time below S-pO2 of 90%) were associated with increased odds of systemic hypertension, diabetes and heart failure but the oxygen desaturation index was only related to hypertension and diabetes. Conclusion Patients with OVS presented with more sleep-related hypoxia, a reduced sleep quality and a higher risk for heart failure and hypertension.The ESADA study group received unrestricted funding grants from the Respironics and Resmed Foundations, and an unrestricted collaboration grant from Bayer AG

Bullying and Victimization in Overweight and Obese Outpatient Children and Adolescents: An Italian Multicentric Study

Objective Being overweight or obese is one of the most common reasons that children and adolescents are teased at school. We carried out a study in order to investigate: i) the relation between weight status and school bullying and ii) the relation between weight status categories and types of victimization and bullying in an outpatient sample of Italian children and adolescents with different degrees of overweight from minimal overweight up to severe obesity. Participants/Methods Nine-hundred-forty-seven outpatient children and adolescents (age range 6.0'14.0 years) were recruited in 14 hospitals distributed over the country of Italy. The participants were classified as normal-weight (N = 129), overweight (N = 126), moderately obese (N = 568), and severely obese (N = 124). The nature and extent of verbal, physical and relational bullying and victimization were assessed with an adapted version of the revised Olweus bully-victim questionnaire. Each participant was coded as bully, victim, bully-victim, or not involved. Results Normal-weight and overweight participants were less involved in bullying than obese participants; severely obese males were more involved in the double role of bully and victim. Severely obese children and adolescents suffered not only from verbal victimization but also from physical victimization and exclusion from group activities. Weight status categories were not directly related to bullying behaviour; however severely obese males perpetrated more bullying behaviour compared to severely obese females. Conclusions Obesity and bullying among children and adolescents are of ongoing concern worldwide and may be closely related. Common strategies of intervention are needed to cope with these two social health challenges

Parameter identification problems in the modelling of cell motility

We present a novel parameter identification algorithm for the estimation of parameters in models of cell motility using imaging data of migrating cells. Two alternative formulations of the objective functional that measures the difference between the computed and observed data are proposed and the parameter identification problem is formulated as a minimisation problem of nonlinear least squares type. A Levenberg–Marquardt based optimisation method is applied to the solution of the minimisation problem and the details of the implementation are discussed. A number of numerical experiments are presented which illustrate the robustness of the algorithm to parameter identification in the presence of large deformations and noisy data and parameter identification in three dimensional models of cell motility. An application to experimental data is also presented in which we seek to identify parameters in a model for the monopolar growth of fission yeast cells using experimental imaging data. Our numerical tests allow us to compare the method with the two different formulations of the objective functional and we conclude that the results with both objective functionals seem to agree

Genetic diversity of Brazilian isolates of feline immunodeficiency virus

We isolated Feline immunodeficiency virus (FIV) from three adult domestic cats, originating from two open shelters in Brazil. Viruses were isolated from PBMC following co-cultivation with the feline T-lymphoblastoid cell line MYA-1. All amplified env gene products were cloned directly into pGL8MYA. The nucleic acid sequences of seven clones were determined and then compared with those of previously described isolates. The sequences of all of the Brazilian virus clones were distinct and phylogenetic analysis revealed that all belong to subtype B. Three variants isolated from one cat and two variants were isolated from each of the two other cats, indicating that intrahost diversity has the potential to pose problems for the treatment and diagnosis of FIV infection