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1.  Systematic Review and Meta-Analysis of Circulating S100B Blood Levels in Schizophrenia 
PLoS ONE  2014;9(9):e106342.
S100B is a calcium-binding protein secreted in central nervous system from astrocytes and other glia cells. High blood S100B levels have been linked to brain damage and psychiatric disorders. S100B levels have been reported to be higher in schizophrenics than healthy controls. To quantify the relationship between S100B blood levels and schizophrenia a systematic literature review of case-control studies published on this topic within July 3rd 2014 was carried out using three bibliographic databases: Medline, Scopus and Web of Science. Studies reporting mean and standard deviation of S100B blood levels both in cases and controls were included in the meta-analysis. The meta-Mean Ratio (mMR) of S100B blood levels in cases compared to controls was used as a measure of effect along with its 95% Confidence Intervals (CI). 20 studies were included totaling for 994 cases and 785 controls. Schizophrenia patients showed 76% higher S100B blood levels than controls with mMR = 1.76 95% CI: 1.44–2.15. No difference could be found between drug-free patients with mMR = 1.84 95%CI: 1.24–2.74 and patients on antipsychotic medication with mMR = 1.75 95% CI: 1.41–2.16). Similarly, ethnicity and stage of disease didn't affect results. Although S100B could be regarded as a possible biomarker of schizophrenia, limitations should be accounted when interpreting results, especially because of the high heterogeneity that remained >70%, even after carrying out subgroups analyses. These results point out that approaches based on traditional categorical diagnoses may be too restrictive and new approaches based on the characterization of new complex phenotypes should be considered.
PMCID: PMC4159239  PMID: 25202915
3.  Transoesophageal endoscopic ultrasound-guided fine-needle aspiration of pleural effusion for the staging of non-small cell lung cancer 
The efficacy of endoscopic ultrasound (EUS) for evaluating mediastinal adenopathy in lung cancer is nowadays proven. However, its accuracy for detection of malignant pleural effusion per se has not been yet investigated. Herein we report our experience with EUS for detecting pleural effusion during the staging procedure of non-small cell lung cancer (NSCLC) patients.
Between January 2009 and December 2011, we performed endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) on 92 selected NSCLC patients to evaluate the T and N factors and to acquire bioptic material and when this was detected, to sample the pleural effusion.
In 10 patients (8 males and 2 females, mean age 66.9 ± 9.2 years) a pleural effusion was detected and sampled. In 7 out of the 10 cases, the cytological examination of the fluid obtained by EUS-FNA tested positive for malignant cells, thereby upgrading the case to Stage IV, irrespective of T and N statuses. In 3 cases the cytology on the EUS-FNA material was proven to be negative for malignancy thereby allowing patients to be treated with curative intent without further delay.
EUS-FNA of the pleural fluid is a safe and simple procedure. Our data, albeit stemming from a limited study population, show that it can be efficient in selected NSCLC cases for obtaining useful material and information with significant impact on the staging and, therefore, on the planning of the optimum therapeutic strategy.
PMCID: PMC3715176  PMID: 23615434
EUS-FNA; NSCLC; Pleural effusion
4.  Erlotinib and Concurrent Chemoradiation in Pretreated NSCLC Patients: Radiobiological Basis and Clinical Results 
BioMed Research International  2013;2013:403869.
Aims. To establish feasibility of the combination of Erlotinib and concurrent chemoradiation in pre-treated patients with locally advanced or metastatic NSCLC. Materials and Methods. Data regarding 60 consecutive patients with NSCLC previously treated with chemotherapy alone were prospectically collected. All patients started Erlotinib concurrently with chemotherapy and radiation delivered to primary tumor. These data were retrospectively analyzed (observational study). Feasibility and toxicity were the primary endpoints, with response rate and progression being the secondary ones, while survival data are reported just as exploratory analysis. The EGFR mutational status was recorded in 32% of cases and it was always wild type. Results. Compliance to the combination protocol was good. Grade 3-4 esophagitis and acute lung toxicity occurred in 2% and 8% of patients, respectively. No progressive disease was recorded in the majority of cases (65%). Median OS and PFS were 23.3 and 4.7 months, respectively. Patients not responding to chemotherapy administered prior to chemoradiation achieved an objective response rate of 53.3% and complete response in 13.3% of cases. Conclusions. The addition of Erlotinib to chemoradiation in inoperable NSCLCs is feasible with interesting efficacy profile. These preliminary results warrant further investigation in patients with locally advanced nonmetastatic NSCLC with EGFR mutations.
PMCID: PMC3747611  PMID: 23984359
5.  Chest wall giant lipoma with a thirty-year history 
Benign chest wall tumours are very uncommon and chest wall lipomas are rarely reported in literature. We report herein a case of a 68-year old man who developed a giant, symptomless mass of the chest wall. A chest computed tomography scan evidenced a solid neoplasm measuring 27 cm in its major axis. A radical excision was performed and the histology was consistent with lipoma. To our knowledge, this is the first case reporting a giant lipoma of the chest wall with a thirty-year history.
PMCID: PMC3397744  PMID: 22588030
Lipoma; Chest wall tumour; Liposarcoma
6.  Intrathoracic gastric perforation: a late complication of an unknown postpartum recurrent hiatal hernia 
Diaphragmatic hernias occurring during pregnancy are an uncommon event. In very rare occasions, the clinical situation can suddenly worsen due to obstruction, torsion or infarction of the herniated viscera. Here, we describe a challenging case of a post-partum diaphragmatic hiatus hernia complicated by intrathoracic gastric perforation. A 23-year old woman was admitted at our hospital with a syndrome characterized by epigastralgy, dyspnoea and fever. She had previously undergone a laparoscopic antireflux surgery for hiatus hernia (6 years before) and a recent (4 months) unremarkable vaginal delivery. Due to the persistence of a pelvic pain after the delivery, she had been taking pain-killers as a self-administered medication. A CT scan showed a massive left pleural effusion and a complete herniation of the stomach into the left hemithorax. After placing a chest drainage and removing up to 3000 ml of brownish purulent fluid, a repeat CT scan (with water soluble contrast swallow) showed a leak at the level of the stomach. At surgery, we observed a complete intrathoracic herniation through a large diaphragmatic hiatal defect and a small well-defined gastric ulcer. A primary repair of both the stomach and the diaphragm was performed. We take the opportunity presented by this report to briefly discuss the patho-physiological mechanisms underlying this unusual complication.
PMCID: PMC3397760  PMID: 22611183
Gastric ulcer; Diaphragmatic hernia; Pleural empyema
8.  EGFR-Targeted Therapy for Non-Small Cell Lung Cancer: Focus on EGFR Oncogenic Mutation 
The two essential requirements for pathologic specimens in the era of personalized therapies for non-small cell lung carcinoma (NSCLC) are accurate subtyping as adenocarcinoma (ADC) versus squamous cell carcinoma (SqCC) and suitability for EGFR molecular testing, as well as for testing of other oncogenes such as EML4-ALK and KRAS. Actually, the value of EGFR expressed in patients with NSCLC in predicting a benefit in terms of survival from treatment with an epidermal growth factor receptor targeted therapy is still in debate, while there is a convincing evidence on the predictive role of the EGFR mutational status with regard to the response to tyrosine kinase inhibitors (TKIs).
This is a literature overview on the state-of-the-art of EGFR oncogenic mutation in NSCLC. It is designed to highlight the preclinical rationale driving the molecular footprint assessment, the progressive development of a specific pharmacological treatment and the best method to identify those NSCLC who would most likely benefit from treatment with EGFR-targeted therapy. This is supported by the belief that a rationale for the prioritization of specific regimens based on patient-tailored therapy could be closer than commonly expected.
PMCID: PMC3575628  PMID: 23423768
EGFR targeted therapy; NSCLC; advanced; mutation; TKIs; resistance.
9.  A pilot survey on the quality of life in respiratory rehabilitation carried out in COPD patients with severe respiratory failure: preliminary data of a novel Inpatient Respiratory Rehabilitation Questionnaire (IRRQ) 
Measuring the state of health is a method for quantifying the impact of an illness on the day-to-day life, health and wellbeing of a patient, providing a quantitative measure of an individual’s quality of life (QoL). QoL expresses patient point of view by a subjective dimension and can express the results of medical intervention. Pulmonary rehabilitation is an essential component in the management of COPD patients, and measuring QoL has become a central focus in the study of this disease.
Although nowadays several questionnaires for measuring the QoL in COPD patients are available, there are no questionnaires specifically developed for evaluating QoL in COPD patients undergoing respiratory rehabilitation.
The aim of this study was to develop a novel questionnaire for the QoL quantification in COPD patients undergoing in-patient pulmonary rehabilitation program.
The questionnaire, administered to COPD patients undergoing long-term oxygen therapy into a respiratory rehabilitation ward, was developed by a simple and graphic layout to be administered to elderly patients. It included one form for admission and another for discharge. It included only tips related to the subjective components of QoL that would be relevant for patient, although likely not strictly related to the respiratory function.
A descriptive analysis was performed for the socio-demographic characteristics and both the non-parametric Wilcoxon T-test and the Cronbach’s alpha index were calculated for evaluating the sensitivity of the questionnaire to the effects of respiratory rehabilitation and for identifying its consistency.
The physical and psychological condition of the 34 COPD patients improved after the rehabilitative treatment and this finding was detected by the questionnaire (overall improvement: 14.2±2.5%), as confirmed by the non-parametric Wilcoxon test (p<0.01). The consistency detected by the Cronbach’s alpha was good for both the questionnaire at admission and at discharge (0.789±0.084 and 0.784±0.145, respectively), although some items did not adequately measure the intended outcome.
This proposed questionnaire represents a substantial innovation compared to previous methods for evaluating the QoL, since it has been specifically designed for hospitalized COPD patients undergoing respiratory rehabilitation with serious respiratory deficiency, allowing to effectively determining the QoL in these patients.
PMCID: PMC3537560  PMID: 23168213
COPD; Inpatients; Quality of Life; Questionnaire; Respiratory rehabilitation
10.  Rationale and clinical benefits of an intensive long-term pulmonary rehabilitation program after oesophagectomy: preliminary report 
Patients who undergo oesophagectomy for oesophagealcancer (OC) usually have an overall poor prognosis and, still more preoccupying, an unsatisfactory quality of life (QoL). Considering that, as already noted, post-operative pulmonary function has a strong correlation with the long-term outcome and QoL after surgery, we have assumed and speculated on the clinical benefits of an intensive long-term pulmonary post-operative rehabilitation program in this particular subset of patients.
Herein, we report the preliminary results of a comparative retrospective analysis in a series of 58 patients who underwent radical oesophagectomy and post-operative chest physical therapy (CPT) under two different protocols, from October 2006 to January 2011.
Finally, we discuss on the time-trend analysis of pulmonary function and the potential role of post-operative pulmonary rehabilitation.
PMCID: PMC3436689  PMID: 22958751
Chest physical therapy; Oesophagectomy; Rehabilitation; Surgery
11.  Systems medicine and integrated care to combat chronic noncommunicable diseases 
Genome Medicine  2011;3(7):43.
We propose an innovative, integrated, cost-effective health system to combat major non-communicable diseases (NCDs), including cardiovascular, chronic respiratory, metabolic, rheumatologic and neurologic disorders and cancers, which together are the predominant health problem of the 21st century. This proposed holistic strategy involves comprehensive patient-centered integrated care and multi-scale, multi-modal and multi-level systems approaches to tackle NCDs as a common group of diseases. Rather than studying each disease individually, it will take into account their intertwined gene-environment, socio-economic interactions and co-morbidities that lead to individual-specific complex phenotypes. It will implement a road map for predictive, preventive, personalized and participatory (P4) medicine based on a robust and extensive knowledge management infrastructure that contains individual patient information. It will be supported by strategic partnerships involving all stakeholders, including general practitioners associated with patient-centered care. This systems medicine strategy, which will take a holistic approach to disease, is designed to allow the results to be used globally, taking into account the needs and specificities of local economies and health systems.
PMCID: PMC3221551  PMID: 21745417
12.  Single center experience on talc poudrage morbidity: focus on high talc dosage 
Malignant pleural effusion (MPE) is a common clinical problem of concern for most of the pneumologists and thoracic surgeons. A general consensus regarding the use of talc poudrage in treatment of MPE exists, but only few studies analyzed in detail talc insufflation related pulmonary morbidity. In particular, ARDS talc-related is caused by physical and chemical effects of the small talc particles (50% particle size <15 μm) and its occurrence is independent from the underlying disease, the quantity of talc used or the technique of talc instillation. In our series we observed 3 cases only (0.75%) of talc-related lung injury. This data strongly confirm the low rate of talc-related lung injury after talc poudrage in treatment of MPE regardless the amount of talc insufflated.
PMCID: PMC3135523  PMID: 21707987
13.  Chemoradiotherapy followed by surgery versus surgery alone in esophageal cancer patients: is it time for additional evidence? 
Recent efforts to improve survival in patients with locally advanced esophageal carcinoma have combined both systemic and local therapy. However, the role of neoadjuvant chemoradiotherapy in technically operable IIa-III esophageal carcinoma is still unresolved.
PMCID: PMC3103440  PMID: 21504620
14.  Posterior mediastinal melanoma causing severe dysphagia: A case report 
We describe an original case of progressive severe dysphagia caused by a posterior mediastinal metastatic melanoma of unknown origin. To the best of our knowledge, such an event has never been described before in the literature.
Case presentation
A progressive severe dysphagia case is reported induced by a melanoma of unknown origin (metastatic to a posterior mediastinal lymph node). At the time of diagnosis, the lesion appeared as a large posterior mediastinal mass mimicking a neurogenic tumour with oesophageal involvement. After complete resection, pathological assessment of the tumour by immunohistochemistry was consistent with nodal metastatic melanoma.
This report of a posterior mediastinal lymph node melanoma is unique. The nodal origin is definitely unusual: a primary melanoma should always be carefully ruled out. In fact no other evidence, a part from the absence of the tumour elsewhere, can support the diagnosis of a primary nodal melanoma.
PMCID: PMC2565681  PMID: 18826613
15.  Molecular Mechanisms of Hexavalent Chromium–Induced Apoptosis in Human Bronchoalveolar Cells 
Hexavalent chromium (Cr[VI]) is classified by the International Agency for Research on Cancer as a group I carcinogen. Although the U.S. Occupational Safety and Health Administration was obliged to reduce the permissible exposure limit (PEL), it was reported that U.S. workers continue to be exposed to dangerously high Cr(VI) levels. In this study, we examined the role of p53 and target genes in a bronchoalveolar carcinoma isogenic cell line system and in primary human bronchial epithelial cells. p53-Negative parental H358 cell line, the same line in which the wild-type p53 expression vector (pC53-SN3) was introduced, and cells obtained from biopsies of human bronchus were exposed to chromate. Induction of DNA strand breaks were evaluated by alkaline elution assay, and apoptosis was analyzed by gel ladder, annexin V-PI staining, and ELISA, whereas p53 and target genes were evaluated by Western blots. Although Cr(VI) induced DNA strand breaks in both H358 cell clones, apoptosis was present only in the p53-transfected cells (H358p53+/+). In these cells, Cr(VI)-induced apoptosis is mediated by p53 upregulation of p53-upregulated modulator of apoptosis (PUMA), BAX translocation to mitochondria, cytochrome c release, and caspase-3 activation. In primary human bronchial epithelial cells expressing functional p53, Cr(VI) induced expression of PUMA and Noxa, which promote apoptosis through BAX. This result establishes p53 as the “necessary” player in Cr(VI)-induced apoptosis. To the best of our knowledge, this is the first report indicating strict correlation of Cr(VI) apoptosis to PUMA induction on primary human bronchoalveolar cells in short-term cultures.
PMCID: PMC2715333  PMID: 16166740
apoptosis; bronchial epithelial cells; hexavalent chromium; p53; PUMA

Results 1-15 (15)