Fears and perception of the impact of COVID-19 on patients with lung cancer. A mono-institutional survey

In February 2020, Italy became one of the first countries to be plagued by the SARS-CoV-2 pandemic, COVID-19. In March 2020, the Italian government decreed a lockdown for the whole country, which overturned communication systems, hospital organization, and access to patients and their relatives and carers. This issue had a particular regard for cancer patients. Our Thoracic Oncology Division therefore reorganized patient access in order to reduce the risk of contagion and, at the same time, encourage the continuation of treatment. Our staff contacted all patients to inform them of any changes in treatment planning, check that they were taking safety measures, and ascertain their feelings and whether they had any COVID-19 symptoms. To better understand patients’ fears and expectations of during the pandemic period, we created a nine-question interview, administered from April to May 2020 to 156 patients with lung cancer. Patients were classified by age, sex, comorbidity, disease stage, prior treatment, and treatment type. The survey showed that during the pandemic period some patients experienced fear of COVID-19, in particular: women (55% vs. 33%), patients with comorbidities (24% vs. 9%), and patients who had already received prior insult (radiotherapy or surgery) on the lung (30% vs. 11%). In addition, the patients who received oral treatment at home or for whom intravenous treatment was delayed, experienced a sense of relief (90% and 72% respectively). However, only 21% of the patients were more afraid of COVID-19 than of their cancer, in particular patients with long-term (> 12 months) vs. short-term cancer diagnosis (28% vs. 12.5%, respectively). Furthermore, the quarantine period or even just the lockdown period alone, worsened the quality of life of some patients (40%), especially those in oral treatment (47%). Our data demonstrate how lung cancer patients are more afraid of their disease than of a world pandemic. Also this interview indirectly highlights the clinician’s major guiding principle in correctly and appropriately managing not just the patient’s expectations of their illness and its treatment, but also and especially of the patient’s fears

Inflammation and neurological adverse drugs reactions: a case of long lasting impaired consciousness after oxatomide administration in a patient with gastroenteritis

Oxatomide at therapeutic doses generates occasionally drowsiness in children. When administered at toxic doses, however oxatomide may induce long lasting impaired consciousness. We now report a case of severe long lasting impaired consciousness induced by therapeutic doses of oxatomide occurring in a child affected by acute gastroenteritis. The clinical symptoms, the pharmacogenetic tests of polymorphisms in cytochrome P450 metabolizing enzymes (CYPs) and the clinical and laboratory analyses indicate that the enhanced drug sedative effect is likely due to an acute, yet mild, inflammatory state of the patient. These findings highlight the importance of assessing common, not serious inflammatory states when oxatomide is prescribed in paediatric patients

Mapeo litológico y mineralógico del batolito devónico Cerro Áspero, usando imágenes ASTER, Sierras Pampeanas Orientales, Argentina

The present study evaluates ASTER image processing as a technique to assist the lithological and mineralogical mapping oflarge granitic bodies and associated hydrothermal alteration assemblages related to the Cerro Áspero batholith, in Sierra de Comechingones, Argentina. This batholith was formed by the successive emplacement of several sub circular, high-level crust plutons that intruded, in the Upper Devonian, to metamorphic sequences of high to medium grade reworked by shear zones. Each of these plutons developed internal, external and roof units, and dyke swarms. Internal units are composed by porphyritic biotite monzogranites and external, roof units and dyke swarms are dominated by two-mica and muscovite leucocratic monzogranites to quarz-rich alkali-feldspar granites. The main associated mineralizations are W-Mo magmatic-hydrothermaldeposits and postbatholith epithemal fluorite deposits of cretaceous age. Supervised classification, principal component analyses and emissivity calculations were made to identify lithological composition and variations within the different plutons that comprise the Cerro Áspero batholith. This methodology allowed us to have a better and precise mapping of the study area as well as the contacts between the different plutons that comprise the Cerro Áspero batholith. The classification with spectral angle mapper methods allowed to identify the different sectors with hydrothermal alteration (argillic and silicification). The argillic alteration is mainly associated with epithermal fluorite deposits74339440

Mapeo litológico y mineralógico del batolito devónico Cerro Áspero, usando imágenes ASTER, Sierras Pampeanas Orientales, Argentina

En este trabajo se presentan los resultados obtenidos utilizando técnicas de procesamiento de imágenes Aster para asistir al mapeo litológico y mineralógico de grandes cuerpos graníticos y de la alteración hidrotermal asociada al batolito Cerro Áspero, Sierra de Comechingones, Argentina. Este batolito fue construido por el emplazamiento sucesivo de varios plutones subcirculares, epizonales, que intruyeron en el Devónico Superior, a secuencias metamórficas de alto a mediano grado retrabajadas por fajas de deformación. Cada uno de estos plutones desarrolló unidades internas, externas, cuspidales y enjambres de diques. Las unidades internas están compuestas de monzogranitos porfídicos con biotita y las unidades externas, cuspidales y los enjambres de dique están dominados por leucogranitos cuyas composiciones varían desde monzogranítica hasta granitos alcali-feldespáticos, ricos en cuarzo. Las principales mineralizaciones asociadas son depósitos magmáticoshidrotermales de W-Mo y depósitos de fluorita epitermal, post-batolíticos, de edad cretácica. Para identificar la composición litológica y las variaciones en los plutones que lo componen se realizó clasificación supervisada, análisis de componentes principales y cálculos de emisividad. Esta metodología permitió un mejor y más detallado mapeo en el área de estudio, así como precisar los contactos entre los plutones que componen el batolito. La clasificación obtenida con el método SAM (spectral angle mapper) permitió la determinación de diferentes alteraciones hidrotermales (argílica y sílicificación). La alteración argílica está asociada principalmente con depósitos de fluorita epitermal.The present study evaluates ASTER image processing as a technique to assist the lithological and mineralogical mapping of large granitic bodies and associated hydrothermal alteration assemblages related to the Cerro Áspero batholith, in Sierra de Comechingones, Argentina. This batholith was formed by the successive emplacement of several sub circular, high-level crust plutons that intruded, in the Upper Devonian, to metamorphic sequences of high to medium grade reworked by shear zones. Each of these plutons developed internal, external and roof units, and dyke swarms. Internal units are composed by porphyritic biotite monzogranites and external, roof units and dyke swarms are dominated by two-mica and muscovite leucocratic monzogranites to quarz-rich alkali-feldspar granites. The main associated mineralizations are W-Mo magmatic-hydrothermal deposits and postbatholith epithemal fluorite deposits of cretaceous age. Supervised classification, principal component analyses and emissivity calculations were made to identify lithological composition and variations within the different plutons that comprise the Cerro Áspero batholith. This methodology allowed us to have a better and precise mapping of the study area as well as the contacts between the different plutons that comprise the Cerro Áspero batholith. The classification with spectral angle mapper methods allowed to identify the different sectors with hydrothermal alteration (argillic and silicification). The argillic alteration is mainly associated with epithermal fluorite deposits.Fil: Radice, Stefania. Universidad Nacional de Río Cuarto. Facultad de Ciencias Exactas, Fisicoquímicas y Naturales. Departamento de Geología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; ArgentinaFil: Pinotti, Lucio Pedro. Universidad Nacional de Río Cuarto. Facultad de Ciencias Exactas, Fisicoquímicas y Naturales. Departamento de Geología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; ArgentinaFil: Maffini, María Natalia. Universidad Nacional de Río Cuarto. Facultad de Ciencias Exactas, Fisicoquímicas y Naturales. Departamento de Geología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; ArgentinaFil: Campanella, Osvaldo Hector. Universidad Nacional de Río Cuarto. Facultad de Ciencias Exactas, Fisicoquímicas y Naturales. Departamento de Geología; ArgentinaFil: Ducart, Diego F.. Universidade Estadual do Campinas. Instituto de Geociencias; BrasilFil: Coniglio, Jorge Enrique. Universidad Nacional de Río Cuarto. Facultad de Ciencias Exactas, Fisicoquímicas y Naturales. Departamento de Geología; ArgentinaFil: Demartis, Manuel. Universidad Nacional de Río Cuarto. Facultad de Ciencias Exactas, Fisicoquímicas y Naturales. Departamento de Geología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; ArgentinaFil: D'eramo, Fernando Javier. Universidad Nacional de Río Cuarto. Facultad de Ciencias Exactas, Fisicoquímicas y Naturales. Departamento de Geología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; Argentin

Contribution of MUTYH variants to male breast cancer risk: results from a multicenter study in Italy

Inherited mutations in BRCA1, and, mainly, BRCA2 genes are associated with increased risk of male breast cancer (MBC). Mutations in PALB2 and CHEK2 genes may also increase MBC risk. Overall, these genes are functionally linked to DNA repair pathways, highlighting the central role of genome maintenance in MBC genetic predisposition. MUTYH is a DNA repair gene whose biallelic germline variants cause MUTYH-associated polyposis (MAP) syndrome. Monoallelic MUTYH variants have been reported in families with both colorectal and breast cancer and there is some evidence on increased breast cancer risk in women with monoallelic variants. In this study, we aimed to investigate whether MUTYH germline variants may contribute to MBC susceptibility. To this aim, we screened the entire coding region of MUTYH in 503 BRCA1/2 mutation negative MBC cases by multigene panel analysis. Moreover, we genotyped selected variants, including p.Tyr179Cys, p.Gly396Asp, p.Arg245His, p.Gly264Trpfs*7, and p.Gln338His, in a total of 560 MBC cases and 1,540 male controls. Biallelic MUTYH pathogenic variants (p.Tyr179Cys/p.Arg241Trp) were identified in one MBC patient with phenotypic manifestation of adenomatous polyposis. Monoallelic pathogenic variants were identified in 14 (2.5%) MBC patients, in particular, p.Tyr179Cys was detected in seven cases, p.Gly396Asp in five cases, p.Arg245His and p.Gly264Trpfs*7 in one case each. The majority of MBC cases with MUTYH pathogenic variants had family history of cancer including breast, colorectal, and gastric cancers. In the case-control study, an association between the variant p.Tyr179Cys and increased MBC risk emerged by multivariate analysis [odds ratio (OR) = 4.54; 95% confidence interval (CI): 1.17-17.58; p = 0.028]. Overall, our study suggests that MUTYH pathogenic variants may have a role in MBC and, in particular, the p.Tyr179Cys variant may be a low/moderate penetrance risk allele for MBC. Moreover, our results suggest that MBC may be part of the tumor spectrum associated with MAP syndrome, with implication in the clinical management of patients and their relatives. Large-scale collaborative studies are needed to validate these findings

Addressing the Role of Angiogenesis in Patients with Advanced Pancreatic Neuroendocrine Tumors Treated with Everolimus: A Biological Prospective Analysis of Soluble Biomarkers and Clinical Outcomes

Simple Summary Despite the approval of new targeted therapies for pancreatic neuroendocrine tumors (PanNETs) over the past decades, the early identification of resistant tumors remains the major challenge, mainly because clear signs of tumor shrinkage are rarely achieved by imaging assessment. Starting from the hypothesis that angiogenesis can be implicated in the resistance to mTOR inhibitors, we evaluated a specific angiogenesis panel (through the measurement of soluble biomarkers for angiogenesis turnover, circulating endothelial cells, and circulating progenitors) as possible predictors of resistance to everolimus or everolimus efficacy in PanNETs. Our study showed that none of the investigated categories of biomarkers had a predictive value for everolimus resistance or efficacy. However, we suggest that circulating endothelial progenitors might be surrogate biomarkers for angiogenesis activity in PanNETs during everolimus treatment, and their baseline levels might correlate with survival outcomes. These data have never been reported before for NETs. Background: The success of targeted therapies in the treatment of pancreatic neuroendocrine tumors has emphasized the strategy of targeting angiogenesis and the PI3K/AKT/mTOR pathway. However, the major challenge in the targeted era remains the early identification of resistant tumors especially when the efficacy is rarely associated to a clear tumor shrinkage at by imaging assessment. Methods: In this prospective study (NCT02305810) we investigated the predictive and prognostic role of soluble biomarkers of angiogenesis turnover (VEGF, bFGF, VEGFR2, TSP-1) circulating endothelial cells and progenitors, in 43 patients with metastatic panNET receiving everolimus. Results: Among all tested biomarkers, we found a specific subpopulation of circulating cells, CD31+CD140b-, with a significantly increased tumor progression hazard for values less or equal to the first quartile. Conclusion: Our study suggested the evidence that circulating cells might be surrogate biomarkers of angiogenesis activity in patients treated with everolimus and their baseline levels can be correlated with survival. However, further studies are now needed to validate the role of these cells as surrogate markers for the selection of patients to be candidates for antiangiogenic treatments

Geology and geocronology of predevonic laminar and irregular intrusions in the central portion of Sierras de Córdoba

El basamento gnéisico-migmático del sector centro-norte de la Sierra Chica y parte oriental de la Sierra Grande de Córdoba, se encuentra asociado a una gran cantidad de intrusiones ígneas, las cuales hasta el momento poseían escasos antecedentes de investigación. En este trabajo, se identificaron cinco litologías ígneas que se agruparon en dos asociaciones en base a su morfología, reología y relaciones de campo. La primera, comprende intrusiones de morfología irregular, que incluyen monzogranitos, tonalitas y pegmatitas (denominadas de tipo I). Estos cuerpos poseen bordes lobulados y contactos transicionales con su roca encajante y su origen posiblemente se vincula con los procesos de anatexis cortical ocurridos durante el ciclo Orogénico Pampeano. La segunda asociación, comprende intrusiones laminares (diques), que incluyen tonalitas-trondhjemitas y pegmatitas (llamadas de tipo II). Se caracterizan por presentar bordes rectos y contactos netos con su roca de caja y se encuentran asociados espacialmente con fajas de cizalla discretas estabilizadas en facies de anfibolitas. A su vez, estas rocas intruyen de manera discordante a las intrusiones irregulares y al basamento gnéisico migmático, por lo que su emplazamiento ha sido posterior. A partir de sus relaciones de yacencia, emplazamiento sin-cinemático con fajas de cizalla (estabilizadas en facies de anfibolita) y las edades Ar/Ar obtenidas en este trabajo (450,92±1,41 Ma y 434,53±3,16 Ma), la generación y el emplazamiento de los cuerpos laminares habría ocurrido durante el Ciclo Orogénico Famatiniano.A large amount of igneous intrusions hosted by a gneissic-migmatic metamorphic basement crop out in the central-north part of the Sierra Chica and eastern boundary of the Sierra Grande de Córdoba. In this contribution, five igneous lithologies were identified and grouped into two distinctive rock groups according to their morphologies, rheology and field relationships. The first group includes irregular-shaped monzogranites, tonalites and pegmatites (called type-I), having lobate and diffuse contacts with their surrounding host rocks. Field relationships suggest that these intrusions originated from crustal anatexis processes of different protoliths, correlated with similar processes occurred during the Pampean Orogeny. The second group includes laminar-shaped (dykes) tonalite-trondhjemites and pegmatites (called type-II), having straight and sharp contacts with their host rocks. They are spatially associated with narrow and localized shear zones stabilized in amphibolite facies. These igneous rocks invariably crosscut the irregular-shaped intrusives of the first group as well as gneissic and migmatic metamorphic host rocks of the basement, clearly reflecting a younger age of emplacement.Fil: Boffadossi, María Alejandra. Universidad Nacional de Rio Cuarto. Facultad de Cs.exactas Fisicoquimicas y Naturales. Instituto de Ciencias de la Tierra, Biodiversidad y Ambiente. - Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Conicet - Cordoba. Instituto de Ciencias de la Tierra, Biodiversidad y Ambiente.; ArgentinaFil: D'eramo, Fernando Javier. Universidad Nacional de Rio Cuarto. Facultad de Cs.exactas Fisicoquimicas y Naturales. Instituto de Ciencias de la Tierra, Biodiversidad y Ambiente. - Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Conicet - Cordoba. Instituto de Ciencias de la Tierra, Biodiversidad y Ambiente.; ArgentinaFil: Demartis, Manuel. Universidad Nacional de Rio Cuarto. Facultad de Cs.exactas Fisicoquimicas y Naturales. Instituto de Ciencias de la Tierra, Biodiversidad y Ambiente. - Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Conicet - Cordoba. Instituto de Ciencias de la Tierra, Biodiversidad y Ambiente.; ArgentinaFil: Pinotti, Lucio Pedro. Universidad Nacional de Rio Cuarto. Facultad de Cs.exactas Fisicoquimicas y Naturales. Instituto de Ciencias de la Tierra, Biodiversidad y Ambiente. - Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Conicet - Cordoba. Instituto de Ciencias de la Tierra, Biodiversidad y Ambiente.; ArgentinaFil: Coniglio, Jorge Enrique. Universidad Nacional de Rio Cuarto. Facultad de Cs.exactas Fisicoquimicas y Naturales. Instituto de Ciencias de la Tierra, Biodiversidad y Ambiente. - Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Conicet - Cordoba. Instituto de Ciencias de la Tierra, Biodiversidad y Ambiente.; ArgentinaFil: Muratori, María Eugenia. Universidad Nacional de Rio Cuarto. Facultad de Cs.exactas Fisicoquimicas y Naturales. Instituto de Ciencias de la Tierra, Biodiversidad y Ambiente. - Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Conicet - Cordoba. Instituto de Ciencias de la Tierra, Biodiversidad y Ambiente.; ArgentinaFil: Maffini, María Natalia. Universidad Nacional de Rio Cuarto. Facultad de Cs.exactas Fisicoquimicas y Naturales. Instituto de Ciencias de la Tierra, Biodiversidad y Ambiente. - Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Conicet - Cordoba. Instituto de Ciencias de la Tierra, Biodiversidad y Ambiente.; ArgentinaFil: Radice, Stefania. Universidad Nacional de Rio Cuarto. Facultad de Cs.exactas Fisicoquimicas y Naturales. Instituto de Ciencias de la Tierra, Biodiversidad y Ambiente. - Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Conicet - Cordoba. Instituto de Ciencias de la Tierra, Biodiversidad y Ambiente.; Argentin

Impact of different exposure models and spatial resolution on the long-term effects of air pollution.

Abstract Long-term exposure to air pollution has been related to mortality in several epidemiological studies. The investigations have assessed exposure using various methods achieving different accuracy in predicting air pollutants concentrations. The comparison of the health effects estimates are therefore challenging. This paper aims to compare the effect estimates of the long-term effects of air pollutants (particulate matter with aerodynamic diameter less than 10 μm, PM10, and nitrogen dioxide, NO2) on cause-specific mortality in the Rome Longitudinal Study, using exposure estimates obtained with different models and spatial resolutions. Annual averages of NO2 and PM10 were estimated for the year 2015 in a large portion of the Rome urban area (12 × 12 km2) applying three modelling techniques available at increasing spatial resolution: 1) a chemical transport model (CTM) at 1km resolution; 2) a land-use random forest (LURF) approach at 200m resolution; 3) a micro-scale Lagrangian particle dispersion model (PMSS) taking into account the effect of buildings structure at 4 m resolution with results post processed at different buffer sizes (12, 24, 52, 100 and 200 m). All the exposures were assigned at the residential addresses of 482,259 citizens of Rome 30+ years of age who were enrolled on 2001 and followed-up till 2015. The association between annual exposures and natural-cause, cardiovascular (CVD) and respiratory (RESP) mortality were estimated using Cox proportional hazards models adjusted for individual and area-level confounders. We found different distributions of both NO2 and PM10 concentrations, across models and spatial resolutions. Natural cause and CVD mortality outcomes were all positively associated with NO2 and PM10 regardless of the model and spatial resolution when using a relative scale of the exposure such as the interquartile range (IQR): adjusted Hazard Ratios (HR), and 95% confidence intervals (CI), of natural cause mortality, per IQR increments in the two pollutants, ranged between 1.012 (1.004, 1.021) and 1.018 (1.007, 1.028) for the different NO2 estimates, and between 1.010 (1.000, 1.020) and 1.020 (1.008, 1.031) for PM10, with a tendency of larger effect for lower resolution exposures. The latter was even stronger when a fixed value of 10 μg/m3 is used to calculate HRs. Long-term effects of air pollution on mortality in Rome were consistent across different models for exposure assessment, and different spatial resolutions

Parent-of-origin-specific allelic associations among 106 genomic loci for age at menarche.

Age at menarche is a marker of timing of puberty in females. It varies widely between individuals, is a heritable trait and is associated with risks for obesity, type 2 diabetes, cardiovascular disease, breast cancer and all-cause mortality. Studies of rare human disorders of puberty and animal models point to a complex hypothalamic-pituitary-hormonal regulation, but the mechanisms that determine pubertal timing and underlie its links to disease risk remain unclear. Here, using genome-wide and custom-genotyping arrays in up to 182,416 women of European descent from 57 studies, we found robust evidence (P < 5 × 10(-8)) for 123 signals at 106 genomic loci associated with age at menarche. Many loci were associated with other pubertal traits in both sexes, and there was substantial overlap with genes implicated in body mass index and various diseases, including rare disorders of puberty. Menarche signals were enriched in imprinted regions, with three loci (DLK1-WDR25, MKRN3-MAGEL2 and KCNK9) demonstrating parent-of-origin-specific associations concordant with known parental expression patterns. Pathway analyses implicated nuclear hormone receptors, particularly retinoic acid and γ-aminobutyric acid-B2 receptor signalling, among novel mechanisms that regulate pubertal timing in humans. Our findings suggest a genetic architecture involving at least hundreds of common variants in the coordinated timing of the pubertal transition

Male breast cancer in BRCA1 and BRCA2 mutation carriers : pathology data from the Consortium of Investigators of Modifiers of BRCA1/2

Background: BRCA1 and, more commonly, BRCA2 mutations are associated with increased risk of male breast cancer (MBC). However, only a paucity of data exists on the pathology of breast cancers (BCs) in men with BRCA1/2 mutations. Using the largest available dataset, we determined whether MBCs arising in BRCA1/2 mutation carriers display specific pathologic features and whether these features differ from those of BRCA1/2 female BCs (FBCs). Methods: We characterised the pathologic features of 419 BRCA1/2 MBCs and, using logistic regression analysis, contrasted those with data from 9675 BRCA1/2 FBCs and with population-based data from 6351 MBCs in the Surveillance, Epidemiology, and End Results (SEER) database. Results: Among BRCA2 MBCs, grade significantly decreased with increasing age at diagnosis (P = 0.005). Compared with BRCA2 FBCs, BRCA2 MBCs were of significantly higher stage (P for trend = 2 x 10(-5)) and higher grade (P for trend = 0.005) and were more likely to be oestrogen receptor-positive [odds ratio (OR) 10.59; 95 % confidence interval (CI) 5.15-21.80] and progesterone receptor-positive (OR 5.04; 95 % CI 3.17-8.04). With the exception of grade, similar patterns of associations emerged when we compared BRCA1 MBCs and FBCs. BRCA2 MBCs also presented with higher grade than MBCs from the SEER database (P for trend = 4 x 10(-12)). Conclusions: On the basis of the largest series analysed to date, our results show that BRCA1/2 MBCs display distinct pathologic characteristics compared with BRCA1/2 FBCs, and we identified a specific BRCA2-associated MBC phenotype characterised by a variable suggesting greater biological aggressiveness (i.e., high histologic grade). These findings could lead to the development of gender-specific risk prediction models and guide clinical strategies appropriate for MBC management.Peer reviewe