Clinical outcome and prognostic factors in renal medullary carcinoma: a pooled analysis from 18 years of medical literature

INTRODUCTION: We describe clinical features and prognostic factors of renal medullary carcinoma (RMC) by performing a pooled analysis of all reported cases since 1995. METHODS: A systematic search was performed to identify all articles describing patients with medullary renal cancer until February 2013. Survivals were estimated using Kaplan-Meier method with 95% confidence intervals and compared across the groups using the log-rank test. The following factors were evaluated using the Cox proportional hazards model: association of extension of disease at diagnosis, response to therapy, and surgical treatment of primary tumour with overall. RESULTS: A total 47 articles were selected; these described 165 patients with RMC plus 1 from our centre. The median age was 21 years and 98% of cases had the sickle cell trait. The mean size of the primary tumours was 6.0 cm, with an involvement of loco-regional lymph nodes in 71% of cases. The overall survival at diagnosis was 4.0 months in metastatic patients and 17.0 months in non-metastatic patients. Patients who received platinum-paclitaxel-gemcitabine had longer control of the disease when compared to topoisomerase inhibitors or targeted therapies. The multivariate analysis confirmed that the advanced stage at diagnosis increased the risk of death of about threefold. CONCLUSION: RMC is a tumour with poorer prognosis; based on these results, platinum-based chemotherapy is the preferred systemic treatment. Even if radical nephrectomy as an up-front strategy did not report a survival benefit, it may be considered to palliate local symptoms and to perform a correct diagnosis

Economic landslide susceptibility under a socio-economic perspective: an application to Umbria Region (Central Italy)

AbstractAn accurate understanding of physical and socio-economic effects of landslides is fundamental to develop more refined risk management, mitigation strategies and land use policies. In this paper we develop a measure to consider the interconnection between physical and economic exposure, i.e. what we call the economic landslide susceptibility, namely the probability of landslide occurrence in an area weighted for its socio-economic exposure considering the real-estate market values. The economic landslide susceptibility is estimated through a method designed for large areas that we applied to the Umbria Region (Central Italy). The method makes use of landslide susceptibility maps and a real estate market value map for any given area under analysis. The innovative concept of economic landslide susceptibility (that is de facto an ex ante landslide cost assessment) may be interpreted as the potential loss that an area might suffer in terms of its propensity for landslides. Useful applications of the proposed method lie in a better territorial management and in the land use planning

Vitamin D and bone metabolism in adult patients with neurofibromatosis type 1

Neurofibromatosis type 1 (NF1) is a genetic multisystemic autosomal dominant disorder determining reduced life expectancy due to higher risk of developing benign and malignant tumors. Low levels of vitamin D and reduced bone mineral density (BMD) have been reported in young patients with NF1. However, correlation between vitamin D and NF1 phenotype needs to be elucidated. Aim of this study was to assess vitamin D levels and bone metabolism in NF1 patients, analyzing potential correlations with clinical phenotype. A cross-sectional study was carried out in a monocentric series of NF1 patients, evaluating genotype, clinical phenotype, BMD, biochemical evaluation with focus on serum 25OH-vitamin D, parathyroid hormone (PTH), calcium and phosphate levels. Correlations between clinical manifestations, neurofibromas, and vitamin D status have been studied in comparison with healthy controls. 31 NF1 adult patients were matched for sex, age and body mass index with 31 healthy controls. A significantly difference in vitamin D level emerged in NF1 patients compared to controls. Interestingly low vitamin D levels correlated with a more aggressive phenotype and with a bigger size of neurofibromas. These data underline that vitamin D deficiency/insufficiency may play a role in clinical severity of neurofibromas in patients with NF1, suggesting the need to check bone status and replace vitamin D in these patients

NeuroDante: Poetry Mentally Engages More Experts but Moves More Non-Experts, and for Both the Cerebral Approach Tendency Goes Hand in Hand with the Cerebral Effort

Neuroaesthetics, the science studying the biological underpinnings of aesthetic experience, recently extended its area of investigation to literary art; this was the humus where neurocognitive poetics blossomed. Divina Commedia represents one of the most important, famous and studied poems worldwide. Poetry stimuli are characterized by elements (meter and rhyme) promoting the processing fluency, a core aspect of neuroaesthetics theories. In addition, given the evidence of different neurophysiological reactions between experts and non-experts in response to artistic stimuli, the aim of the present study was to investigate, in poetry, a different neurophysiological cognitive and emotional reaction between Literature (L) and Non-Literature (NL) students. A further aim was to investigate whether neurophysiological underpinnings would support explanation of behavioral data. Investigation methods employed: self-report assessments (recognition, appreciation, content recall) and neurophysiological indexes (approach/withdrawal (AW), cerebral effort (CE) and galvanic skin response (GSR)). The main behavioral results, according to fluency theories in aesthetics, suggested in the NL but not in the L group that the appreciation/liking went hand by hand with the self-declared recognition and with the content recall. The main neurophysiological results were: (i) higher galvanic skin response in NL, whilst higher CE values in L; (ii) a positive correlation between AW and CE indexes in both groups. The present results extended previous evidence relative to figurative art also to auditory poetry stimuli, suggesting an emotional attenuation “expertise-specific” showed by experts, but increased cognitive processing in response to the stimuli

Derivation of a linearised elasticity model from singularly perturbed multiwell energy functionals

Linear elasticity can be rigorously derived from finite elasticity under the assumption of small loadings in terms of Gamma-convergence. This was first done in the case of one-well energies with super-quadratic growth and later generalised to different settings, in particular to the case of multi-well energies where the distance between the wells is very small (comparable to the size of the load). In this paper we study the case when the distance between the wells is independent of the size of the load. In this context linear elasticity can be derived by adding to the multi-well energy a singular higher order term which penalises jumps from one well to another. The size of the singular term has to satisfy certain scaling assumptions whose optimality is shown in most of the cases. Finally, the derivation of linear elasticty from a two-well discrete model is provided, showing that the role of the singular perturbation term is played in this setting by interactions beyond nearest neighbours

Bollettino Sismico Italiano: Analisys of Early Aftershocks of the 2016 MW 6.0 Amatrice, MW 5.9 Visso and MW 6.5 Norcia earthquakes in Central Italy

The Amatrice-Visso-Norcia seismic sequence is the most important of the last 30 years in Italy. The seismic sequence started on 24 August, 2016 and still is ongoing in central Apennines. At the end of February 2017 more than 57,000 events were located, 80,000 events up to the end of September 2017 (Fig. 1). The mainshocks of the sequence occurred on 24 August 2016 (Mw 6.0 and Mw 5.4), 26 October 2016 (Mw 5.4 and Mw 5.9), 30 October 2016 (Mw 6.5), 18 January 2017 (four earthquakes Mw≥ 5.0). In this seismic sequence, all the waveforms recorded by temporary stations deployed by the SISMIKO emergency group (stations T12**; Moretti et al., 2016) where available in real- time at the surveillance room of INGV. Because of the high level of seismicity and the dense seismic network installed in the region, more than 150 events per day were located at the end of February 2017; still 60 events per day were located up to the end of August 2017.The Amatrice-Visso-Norcia is the most important seismic sequence since 2015, the time when the analysis procedures of the BSI group (Bollettino Sismico Italiano) were revised (Nardi et al., 2015). BSI is now available every four months on the web: bulletins contain revised earthquakes (location and magnitude) with ML≥ 1.5, quasi-real time revision of ML≥ 3.5 earthquakes and phase arrivals from waveforms recorded on seismic stations available from the European Integrated Data Archive (EIDA), (Mazza et al., 2012). These last procedures allow the integration of signals from temporary seismic stations (Moretti et al., 2014) installed by the emergency group SISMIKO (Moretti and Sismiko working group, 2016), even when they are not in real time transmission, if they are rapidly archived in EIDA, together with real time signals from the seismic stations of the permanent INGV network. The analysis strategy of the BSI group for the Amatrice -Visso - Norcia seismic sequence (AVN.s.s in the following) was to select the earthquakes located in the box with min/max latitude: 42.2/43.2 - and min/max longitude: 12.4/14.1 to prepare a special volume of BSI on the seismic sequence.PublishedTrieste, Italy1SR. TERREMOTI - Servizi e ricerca per la Societ

Carriers of ADAMTS13 Rare Variants Are at High Risk of Life-Threatening COVID-19

Thrombosis of small and large vessels is reported as a key player in COVID-19 severity. However, host genetic determinants of this susceptibility are still unclear. Congenital Thrombotic Thrombocytopenic Purpura is a severe autosomal recessive disorder characterized by uncleaved ultra-large vWF and thrombotic microangiopathy, frequently triggered by infections. Carriers are reported to be asymptomatic. Exome analysis of about 3000 SARS-CoV-2 infected subjects of different severities, belonging to the GEN-COVID cohort, revealed the specific role of vWF cleaving enzyme ADAMTS13 (A disintegrin-like and metalloprotease with thrombospondin type 1 motif, 13). We report here that ultra-rare variants in a heterozygous state lead to a rare form of COVID-19 characterized by hyper-inflammation signs, which segregates in families as an autosomal dominant disorder conditioned by SARS-CoV-2 infection, sex, and age. This has clinical relevance due to the availability of drugs such as Caplacizumab, which inhibits vWF-platelet interaction, and Crizanlizumab, which, by inhibiting P-selectin binding to its ligands, prevents leukocyte recruitment and platelet aggregation at the site of vascular damage

An explainable model of host genetic interactions linked to COVID-19 severity

We employed a multifaceted computational strategy to identify the genetic factors contributing to increased risk of severe COVID-19 infection from a Whole Exome Sequencing (WES) dataset of a cohort of 2000 Italian patients. We coupled a stratified k-fold screening, to rank variants more associated with severity, with the training of multiple supervised classifiers, to predict severity based on screened features. Feature importance analysis from tree-based models allowed us to identify 16 variants with the highest support which, together with age and gender covariates, were found to be most predictive of COVID-19 severity. When tested on a follow-up cohort, our ensemble of models predicted severity with high accuracy (ACC = 81.88%; AUCROC = 96%; MCC = 61.55%). Our model recapitulated a vast literature of emerging molecular mechanisms and genetic factors linked to COVID-19 response and extends previous landmark Genome-Wide Association Studies (GWAS). It revealed a network of interplaying genetic signatures converging on established immune system and inflammatory processes linked to viral infection response. It also identified additional processes cross-talking with immune pathways, such as GPCR signaling, which might offer additional opportunities for therapeutic intervention and patient stratification. Publicly available PheWAS datasets revealed that several variants were significantly associated with phenotypic traits such as "Respiratory or thoracic disease", supporting their link with COVID-19 severity outcome.A multifaceted computational strategy identifies 16 genetic variants contributing to increased risk of severe COVID-19 infection from a Whole Exome Sequencing dataset of a cohort of Italian patients

The polymorphism L412F in TLR3 inhibits autophagy and is a marker of severe COVID-19 in males

The polymorphism L412F in TLR3 has been associated with several infectious diseases. However, the mechanism underlying this association is still unexplored. Here, we show that the L412F polymorphism in TLR3 is a marker of severity in COVID-19. This association increases in the sub-cohort of males. Impaired macroautophagy/autophagy and reduced TNF/TNFα production was demonstrated in HEK293 cells transfected with TLR3L412F-encoding plasmid and stimulated with specific agonist poly(I:C). A statistically significant reduced survival at 28 days was shown in L412F COVID-19 patients treated with the autophagy-inhibitor hydroxychloroquine (p = 0.038). An increased frequency of autoimmune disorders such as co-morbidity was found in L412F COVID-19 males with specific class II HLA haplotypes prone to autoantigen presentation. Our analyses indicate that L412F polymorphism makes males at risk of severe COVID-19 and provides a rationale for reinterpreting clinical trials considering autophagy pathways. Abbreviations: AP: autophagosome; AUC: area under the curve; BafA1: bafilomycin A1; COVID-19: coronavirus disease-2019; HCQ: hydroxychloroquine; RAP: rapamycin; ROC: receiver operating characteristic; SARS-CoV-2: severe acute respiratory syndrome coronavirus 2; TLR: toll like receptor; TNF/TNF-α: tumor necrosis factor