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Biomedical subjects

Stefano Gasparini

Publications and source records attributed to Stefano Gasparini.

6 recordsLinked to original sources

Adeno-Associated Virus Type 5 Infection via PDGFRα Is Associated With Interstitial Lung Disease in Systemic Sclerosis and Generates Composite Peptides and Epitopes Recognized by the Agonistic Immunoglobulins Present in Patients With Systemic Sclerosis.

OBJECTIVE: The etiopathogenesis of systemic sclerosis (SSc) is unknown. Platelet-derived growth factor receptors (PDGFRs) are overexpressed in patients with SSc. Because PDGFR&#x3b1; is targeted by the adeno-associated virus type 5 (AAV5), we investigated whether AAV5 forms a complex with PDGFR&#x3b1; exposing epitopes that may induce the immune responses to the virus-PDGFR&#x3b1; complex. METHODS: The binding of monomeric human PDGFR&#x3b1; to the AAV5 capsid was analyzed by in silico molecular docking, surface plasmon resonance (SPR), and genome editing of the PDGFR&#x3b1; locus. AAV5 was detected in SSc lungs by in situ hybridization, immunohistochemistry, confocal microscopy, and molecular analysis of bronchoalveolar lavage (BAL) fluid. Immune responses to AAV5 and PDGFR&#x3b1; were evaluated by SPR using SSc monoclonal anti-PDGFR&#x3b1; antibodies and immunoaffinity-purified anti-PDGFR&#x3b1; antibodies from sera of patients with SSc. RESULTS: AAV5 was detected in the BAL fluid of 41 of 66 patients with SSc with interstitial lung disease (62.1%) and in 17 of 66 controls (25.75%) (P <&#x2009;0.001). In SSc lungs, AAV5 localized&#x2009;in type II pneumocytes and in interstitial cells. A molecular complex formed of spatially contiguous epitopes of the AAV5 capsid and of PDGFR&#x3b1; was identified and characterized. In silico molecular docking analysis and binding to the agonistic anti-PDGFR&#x3b1; antibodies identified spatially contiguous epitopes derived from PDGFR&#x3b1; and AAV5 that interacted with SSc agonistic antibodies to PDGFR&#x3b1;. These peptides were also able to bind total IgG isolated from patients with SSc, not from healthy controls. CONCLUSION: These data link AVV5 with the immune reactivity to endogenous antigens in SSc and provide a novel element in the pathogenesis of SSc.

Humans↗

Extended tracheal resection for chondroma.

We report a case of a 43-year-old man who underwent an extended resection of the lower trachea for primary chondroma. Tracheal chondroma is a rare benign disease, arising from the cartilaginous rings, that grows intra-luminally or extends through the tracheal wall determining an obstructing syndrome. The endoscopy may be useful for diagnosis and palliative treatment, but the tracheal resection is recommended because the risk of recurrence or malignant transformation.

Adult↗

Evolving role of interventional pulmonology in the interdisciplinary approach to the staging and management of lung cancer: bronchoscopic mediastinal staging of lung cancer.

Mediastinal lymph node involvement is present in 26%-38% of patients with non-small-cell lung cancer at the time of diagnosis, and it is often the most significant factor in determining surgical resectability. Complete and accurate mediastinal staging of lung cancer is essential for determining prognosis and for guiding optimal treatment strategies. Computed tomography and positron emission tomography are the most widely used noninvasive means for mediastinal staging in lung cancer. However, based on their reported specificities, computed tomography and positron emission tomography findings should be verified by cytohistologic sampling. In recent decades, the technique of transbronchial needle aspiration (TBNA) has been developed, permitting the bronchoscopist to obtain cytohistologic material from the hilar and mediastinal lymph nodes adjacent to the tracheobronchial wall. The technique of TBNA has a great specificity, is safe and cost-effective compared with surgical methods, and can be performed during the initial diagnostic bronchoscopy. Transbronchial needle aspiration sensitivity is 76%-78% but is highly influenced by several factors. Endobronchial ultrasound has been proposed as a means for improving TBNA sensitivity. Recently, a new type of bronchoscope with a built-in convex ultrasound probe directly attached to the tip has been developed to guide TBNA under real-time imaging. Reports on this innovative technique reveal a sensitivity of 94%-95.7%, which is superior to the reported sensitivity of surgical methods. However, ultrasound-guided TBNA and traditional TBNA should be considered complementary techniques, because their integration is likely to become the optimal staging strategy for patients with lung cancer.

Biopsy, Needle↗

An unusual iatrogenic foreign body (surgical gauze) in the trachea.

We report the case of a 60-year-old male with history of surgery for tracheal stenosis 21 years prior to the onset of difficult asthma-like symptoms. Upon exploring the tracheobronchial tree using the fiberoptic bronchoscope, a surgical gauze was found. The foreign body migrated transluminally from the mediastinum into the trachea and its removal was possible with rigid bronchoscopy leading to a rapid recovery of his symptoms.

Bronchoscopy↗

Risk assessment of patients with hematologic malignancies who develop fever accompanied by pulmonary infiltrates: a historical cohort study.

BACKGROUND: The mortality rate associated with fever accompanied by pulmonary infiltrates after chemotherapy for hematologic malignancies remains higher than the corresponding rate associated with febrile neutropenia without pulmonary infiltrates. Nonetheless, few studies have focused on the factors that predict outcome for patients with lung infiltrates. The purpose of the current study was to construct a risk model for clinical use by assessing the factors that affect outcome for patients with fever and pulmonary infiltrates. METHODS: A historical cohort of 110 patients with hematologic malignancies who developed fever and pulmonary infiltrates was examined. Using parameters for which data were available at the onset of lung infiltrates, univariate and multivariate analyses were performed to assess factors affecting outcome. After a value of one point was assigned to each significant variable, a prediction score was calculated for each patient; scores were used to generate a system for identifying patients with a low risk of death due to fever accompanied by pulmonary infiltrates. RESULTS: The crude mortality rate associated with pulmonary infiltrates was 23%; factors associated with cure included a favorable change in white blood cell counts (odds ratio [OR], 5.6; 95% confidence interval [CI], 1.7-18.9; P = 0.001), C-reactive protein levels < 10 mg/dL (OR, 4.6; 95% CI, 1.6-13.8; P = 0.001), and serum albumin levels > or = 3 g/dL (OR, 3.2; 95% CI, 1.4-7.3; P = 0.004). Low-risk patients (risk score, 2-3) and high-risk patients (risk score, 0-1) had survival rates of 95% and 46%, respectively (P < 0.0001). The risk model had a specificity of 88% and a positive predictive value of 95%. CONCLUSIONS: The risk model tested in the current study accurately predicted the survival of patients with hematologic malignancies who developed fever with pulmonary infiltrates. Once prospectively validated, the model could be used to select patients for trials involving novel diagnostic and therapeutic strategies.

Age Distribution↗