86 research outputs found
What information could the main actors of liquid biopsy provide? A representative case of non-small cell lung cancer (NSCLC)
In non-small cell lung cancer (NSCLC), there is a consensus regarding the use of liquid biopsy, generally, to detect "druggable" mutations and, in particular, to monitor tyrosine kinase inhibitor (TKI) treatments. However, whether circulating tumor cells (CTCs) are better tools than cell-free DNA (cfDNA), is still a matter of debate, mainly concerning which antigen(s) we should use to investigating simultaneously both epithelial and epithelial-to-mesenchymal transient (EMT) phenotype in the same sample of CTCs. To address this item, we exploited here a single-tube liquid biopsy, to detect both epithelial cell adhesion molecule (EpCAM)-positive CTCs and EpCAM-low/negative CTCs, because down-modulation of EpCAM is considered the first step in EMT. Furthermore, we analyzed the DNA from CTCs of four different phenotypes (ctcDNA), according to their EpCAM expression and cytokeratin pattern, and circulating tumor DNA (ctDNA) by droplet digital PCR (ddPCR), in order to disclose activating and resistancedriving mutations. Liquid biopsy reflected spatial and temporal heterogeneity of the tumor under treatment pressure. We provide the proof-of-concept that the complementary use of ctDNA and ctcDNA represents a reliable, minimally invasive and dynamic tool for a more comprehensive view of tumor evolution
Amiodarone-induced pulmonary toxicity with an excellent response to treatment
Amiodarone is an anti-arrhythmic drug widely used, but its administration can be associated with several adverse side-effects. Among these, amiodarone-induced pulmonary toxicity (APT) occurs in 4-17% of cases and, if not early diagnosed and treated, may evolve towards pulmonary fibrosis and respiratory failure. A 76 years-old-man went to the hospital for accidental trauma. The patient did not report respiratory symptoms but was suffering from atrial fibrillation treated with amiodarone 200 mg/day from three years (cumulative dose >150 gr). HRCT showed ground-glass opacities and nodules in both lungs. The patient underwent fibreoptic bronchoscopy with BAL. Cytologic examination of BALF sediment put in evidence foamy macrophages. The electronic microscopy revealed into the alveolar macrophages "⊠the presence of multilamellar intracytoplasmic bodies and lysosomes, loads of lipid material". LFTs showed a restrictive syndrome and an impairment of DLCO. Amiodarone discontinuation and steroid administration led to the regression of radiological lesions and the recovery of lung function. Patients taking amiodarone can experience APT. They should perform a basal chest x-ray with LFTs before starting therapy. Monitoring could reveal early the pulmonary toxicity, and patients can respond favourably to the treatment
Upgrading Monocytes Therapy for Critical Limb Ischemia Patient Treatment: Pre-Clinical and GMP-Validation Aspects
Advanced cell therapy medicinal products (ATMP) are at the forefront of a new range of biopharmaceuticals. The use of ATMP has evolved and increased in the last decades, representing a new approach to treating diseases that are not effectively managed with conventional treatments. The standard worldwide recognized for drug production is the Good Manufacturing Practices (GMP), widely used in the pharma production of synthesized drugs but applying also to ATMP. GMP guidelines are worldwide recognized standards to manufacture medicinal products to guarantee high quality, safety, and efficacy. In this report, we describe the pre-clinical and the GMP upgrade of peripheral blood mononuclear cell (PBMC) preparation, starting from peripheral blood and ending up with a GMP-grade clinical product ready to be used in patients with critical limb ischemia (CLI). We also evaluated production in hypoxic conditions to increase PBMC functional activity and angiogenic potential. Furthermore, we extensively analyzed the storage and transport conditions of the final product as required by the regulatory body for ATMPs. Altogether, results suggest that the whole manufacturing process can be performed for clinical application. Peripheral blood collected by a physician should be transported at room temperature, and PBMCs should be isolated in a clean room within 8 h of venipuncture. Frozen cells can be stored in nitrogen vapors and thawed for up to 12 months. PBMCs resuspended in 5% human albumin solution should be stored and transported at 4 degrees C before injection in patients within 24 h to thawing. Hypoxic conditioning of PBMCs should be implemented for clinical application, as it showed a significant enhancement of PBMC functional activity, in particular with increased adhesion, migration, and oxidative stress resistance. We demonstrated the feasibility and the quality of a GMP-enriched suspension of monocytes as an ATMP, tested in a clean room facility for all aspects related to production in respect of all the GMP criteria that allow its use as an ATMP. We think that these results could ease the way to the clinical application of ATMPs
Retrospective assessment of inguinal hernia repair in elderly outpatients
Background In the last ten years Day Surgery has significantly evolved, due to improvements in surgery and anaesthesia, and the need of reducing long term admission costs [1]. However, is Day Surgery suitable for elderly patients? The aim of this paper is to assess the risk of over 70 year-old outpatients who underwent inguinal hernia repair, and suggest an adequate preoperative pathway
Idiopathic Pulmonary Fibrosis (IPF) incidence and prevalence in Italy
Background: Studies of Idiopathic Pulmonary Fibrosis (IPF) epidemiology show regional variations of
incidence and prevalence; no epidemiological studies have been carried out in Italy. Objective: To determine incidence
and prevalence rates of IPF in the population of a large Italian region.Methods: in this cross-sectional study
study data were collected on all patients of 18 years of age and older admitted as primary or secondary idiopathic
fibrosing alveolitis (ICD9-CM 516.3) to Lazio hospitals, from 1/1/2005 to 31/12/2009, using regional hospital
discharge, population and cause of death databases. Reporting accuracy was assessed on a random sample of hospital
charts carrying the ICD9-CM 516.3, 516.8, 516.9 and 515 codes, by reviewing radiology and pathology
findings to define cases as IPF âconfidentâ, âpossibleâ or âinconsistentâ. Results: Annual prevalence and incidence
of IPF were estimated at 25.6 per 100,000 and 7.5 per 100,000 using the ICD9-CM code 516.3 without chart
audit while they were estimated at 31.6 per 100,000 and at 9,3 per 100,000 for the IPF âconfidentâ definition after
hospital chart audit. Conclusion: The data provide a first estimate of IPF incidence in Italy and indicate that incidence
and prevalence in southern European regions may be similar to those observed in northern Europe and
North America. (Sarcoidosis Vasc Diffuse Lung Dis 2014; 31: 191-197
Cavernostomy x Resection for Pulmonary Aspergilloma: A 32-Year History
<p>Abstract</p> <p>Background</p> <p>The most adequate surgical technique for the treatment of pulmonary aspergilloma is still controversial. This study compared two groups of patients submitted to cavernostomy and pulmonary parenchyma resection.</p> <p>Methods</p> <p>Cases of pulmonary aspergilloma operated upon between 1979 and 2010 were analyzed retrospectively. Group 1 consisted of patients submitted to cavernostomy and group 2 of patients submitted to pulmonary parenchyma resection. The following variables were compared between groups: gender, age, number of hospitalizations, pre- and postoperative length of hospital stay, time of follow-up, location and type of aspergilloma, preoperative symptoms, underlying disease, type of fungus, preoperative pulmonary function, postoperative complications, patient progression, and associated diseases.</p> <p>Results</p> <p>A total of 208 patients with pulmonary aspergilloma were studied (111 in group 1 and 97 in group 2). Group 1 was older than group 2. The number of hospitalizations, length of hospital stay and time of follow-up were higher in group 1. Hemoptysis was the most frequent preoperative symptom in group 1. Preoperative respiratory malfunction was more severe in group 1. Hemorrhagic complications and recurrence were more frequent in group 1 and infectious complications and residual pleural space were more common in group 2. Postoperative dyspnea was more frequent in group 2. Patient progression was similar in the two groups. No difference in the other factors was observed between groups.</p> <p>Conclusions</p> <p>Older patients with severe preoperative respiratory malfunction and peripheral pulmonary aspergilloma should be submitted to cavernostomy. The remaining patients can be treated by pulmonary resection.</p
The Molecular Mechanism of Intestinal Levodopa Absorption and Its Possible Implications for the Treatment of Parkinsonâs Disease
Variação na prevalĂȘncia de asma e atopia em um grupo de escolares de Porto Alegre, Rio Grande do Sul
Human lung adenocarcinoma cell cultures derived from malignant pleural effusions as model system to predict patients chemosensitivity
Gli storici e la Lineare B, Cinquantâanni dopo, Atti del Convegno Internazionale tenutosi a Firenze il 24-25 novembre 2003.
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