Silvia Quadrelli

Bio: Silvia Quadrelli is an academic researcher from British Hospital. The author has contributed to research in topics: Lung cancer & Idiopathic pulmonary fibrosis. The author has an hindex of 18, co-authored 110 publications receiving 1095 citations. Previous affiliations of Silvia Quadrelli include University of Buenos Aires.

Multiplexed methylation profiles of tumor suppressor genes and clinical outcome in lung cancer.

Abstract: Changes in DNA methylation of crucial cancer genes including tumor suppressors can occur early in carcinogenesis, being potentially important early indicators of cancer. The objective of this study was to examine a multiplexed approach to assess the methylation of tumor suppressor genes as tumor stratification and clinical outcome prognostic biomarkers for lung cancer. A multicandidate probe panel interrogated DNA for aberrant methylation status in 18 tumor suppressor genes in lung cancer using a methylation-specific multiplex ligation-dependent probe amplification assay (MS-MLPA). Lung cancer cell lines (n = 7), and primary lung tumors (n = 54) were examined using MS-MLPA. Genes frequently methylated in lung cancer cell lines including SCGB3A1, ID4, CCND2 were found among the most commonly methylated in the lung tumors analyzed. HLTF, BNIP3, H2AFX, CACNA1G, TGIF, ID4 and CACNA1A were identified as novel tumor suppressor candidates methylated in lung tumors. The most frequently methylated genes in lung tumors were SCGB3A1 and DLC1 (both 50.0%). Methylation rates for ID4, DCL1, BNIP3, H2AFX, CACNA1G and TIMP3 were significantly different between squamous and adenocarcinomas. Methylation of RUNX3, SCGB3A1, SFRP4, and DLC1 was significantly associated with the extent of the disease when comparing localized versus metastatic tumors. Moreover, methylation of HTLF, SFRP5 and TIMP3 were significantly associated with overall survival. MS-MLPA can be used for classification of certain types of lung tumors and clinical outcome prediction. This latter is clinically relevant by offering an adjunct strategy for the clinical management of lung cancer patients.

Pulmonary involvement of systemic lupus erythematosus: analysis of 90 necropsies.

Abstract: Pleuropulmonary manifestations of systemic lupus erythematosus (SLE) have been reported to be of variable prevalence, depending on the diagnostic methods used. The objective of this study was to determine the anatomopathological prevalence and the nature of lung involvement associated with SLE and to define if there were differences in the grade and type of pulmonary involvement in patients who had died at different time periods, before or after 1996. Complete autopsy studies of 90 patients with SLE diagnosis carried out between 1958 and 2006 and their clinical records were studied. All patients fulfilled the American College of Rheumathology (ACR) diagnostic criteria for SLE. Two groups of patients were analyzed: patients who had died before 1996 and those deceased in 1996-2006. Some pleuropulmonary involvement was detected in 97.8% of the autopsies. The most frequent findings were pleuritis (77.8%), bacterial infections (57.8%), primary and secondary alveolar haemorrhages (25.6%), followed by distal airway alterations (21.1%), opportunistic infections (14.4%) and pulmonary thromboembolism (7.8%), both acute and chronic. No cases of acute or chronic lupus pneumonitis were found. Opportunistic lung infections were invasive aspergillosis, disseminated strongyloidiasis, mucormicosis and Pneumocystis carinii. Only three of 23 patients with alveolar haemorrhage showed capillaritis. The four patients with primary pulmonary hypertension (PHT) had plexiform lesions. Deceased patients' age at death (46.09 +/- 11.01 vs 30.3 +/- 11.5 years, P < 0.0001) as well as survival time from diagnosis date (11.8 +/- 11.2 vs 4.4 +/- 4.9 years, P < 0.0001) in the second time period evaluated were significantly higher. However, there were no statistically significant differences in the prevalence of any of the pulmonary manifestations. Sepsis was considered the major cause of death without significant differences in both groups. Our results show that pulmonary manifestations directly caused by systemic lupus erythematosus are very uncommon and that their prevalence has not changed in the past 10 years. Pulmonary infection is still the most frequent affection, and it is an important cause of death in patients with lupus.

Is Asthma in the Elderly Really Different

Abstract: To examine the nature of asthma in the elderly, we compared older (group 1: 65 years or older, n = 50) with younger patients (group 2: 1 was lower in older patients (54.4 ± 17.3 vs. 71.8 ± 18.5%, p {FC96}& 0.001). Patients with early-onset asthma showed more frequently shorter symptom-free periods (93.3 vs. 53.3%, p 1 (group 1: 66.7 ± 13.7% vs. group 2: 90.3 ± 15.1%, p 1 (46.2 ± 13.1 vs. 61.0 ± 13.2%, p 1, shorter symptom-free periods and a lesser proportion of patients with only mild symptoms were observed in patients older than 65 with early-onset asthma compared with those younger than 40 years. Elderly patients with a shorter duration of asthma were not different from young patients. Our study strongly suggests that severity of asthma and development of irreversible airflow obstruction depend on the duration of disease.

An Official ATS/ERS/JRS/ALAT Statement: Idiopathic Pulmonary Fibrosis: Evidence-Based Guidelines for Diagnosis and Management

Abstract: This document is an international evidence-based guideline on the diagnosis and management of idiopathic pulmonary fibrosis, and is a collaborative effort of the American Thoracic Society, the European Respiratory Society, the Japanese Respiratory Society, and the Latin American Thoracic Association. It represents the current state of knowledge regarding idiopathic pulmonary fibrosis (IPF), and contains sections on definition and epidemiology, risk factors, diagnosis, natural history, staging and prognosis, treatment, and monitoring disease course. For the diagnosis and treatment sections, pragmatic GRADE evidence-based methodology was applied in a question-based format. For each diagnosis and treatment question, the committee graded the quality of the evidence available (high, moderate, low, or very low), and made a recommendation (yes or no, strong or weak). Recommendations were based on majority vote. It is emphasized that clinicians must spend adequate time with patients to discuss patients' values and preferences and decide on the appropriate course of action.

The Law of Peoples

Abstract: The Law of Peoples John Rawls Harvard 1999 John Rawls, the great political philosopher, has turned his reflections to questions of international justice, much as his philosophical ancestor Kant did toward the end of his career. Indeed, Kant's conception of a "pacific federation" of states in Perpetual Peace is Rawls's acknowledged model for the "realistic utopia" sketched in The Law of Peoples, which expands upon his 1993 essay by the same title (without, however, revising its basic argument). Despite differing philosophical constraints and geopolitical conditions, both Kant and Rawls aim to develop an ideal normative framework for international law that accommodates a measure of realism and rejects the idea of a world-state. Unfortunately, in its uncritical acceptance of so-called "decent hierarchical societies" even at the level of ideal theory, the normative claim of Rawls's Law of Peoples is undermined. This philosophical appeasement, meant to secure perpetual peace in our time through a moderately demanding Law of Peoples that liberal and "decent" hierarchical societies alike can endorse, departs fundamentally from Kant's cosmopolitanism. For Kant, the "First Definitive Article of a Perpetual Peace-as opposed to a temporary interruption of hostilities-is that each member state of the foedus pacif cum must have a republican form of government, which is partly founded upon "the principle of legal equality for everyone (as citizens)." By contrast, Rawls weakens his ideal of international justice to buy the assent of hierarchical societies, which by definition lack equality among citizens, at the price of sacrificing a theoretical basis for justifying reforms of the practices and institutions of these hierarchical societies above a minimal level of decency. Rawls's complex argument begins by extending the original position, in which principles of justice for the basic structure of society are chosen under epistemic constraints that ensure fairness, from a single liberal society to what he calls the Society of Liberal Peoples. In a second step, though still within ideal theory, he argues that the substantive principles comprising the Law of Peoples are also acceptable to decent hierarchical societies, which possess decent consultation hierarchies and common good conceptions of justice. Despite being inegalitarian, decent hierarchical societies do respect basic human rights, allow some dissent, and at least consult with representatives of groups whose members are denied full citizenship rights. …

Deep learning for chest radiograph diagnosis: A retrospective comparison of the CheXNeXt algorithm to practicing radiologists

Abstract: Background Chest radiograph interpretation is critical for the detection of thoracic diseases, including tuberculosis and lung cancer, which affect millions of people worldwide each year. This time-consuming task typically requires expert radiologists to read the images, leading to fatigue-based diagnostic error and lack of diagnostic expertise in areas of the world where radiologists are not available. Recently, deep learning approaches have been able to achieve expert-level performance in medical image interpretation tasks, powered by large network architectures and fueled by the emergence of large labeled datasets. The purpose of this study is to investigate the performance of a deep learning algorithm on the detection of pathologies in chest radiographs compared with practicing radiologists.