40 research outputs found

    Neutralization of IFN-γ reverts clinical and laboratory features in a mouse model of macrophage activation syndrome.

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    BACKGROUND: The pathogenesis of macrophage activation syndrome (MAS) is not clearly understood: a large body of evidence supports the involvement of mechanisms similar to those implicated in the setting of primary hemophagocytic lymphohistiocytosis. OBJECTIVE: We sought to investigate the pathogenic role of IFN-γ and the therapeutic efficacy of IFN-γ neutralization in an animal model of MAS. METHODS: We used an MAS model established in mice transgenic for human IL-6 (IL-6TG mice) challenged with LPS (MAS mice). Levels of IFN-γ and IFN-γ-inducible chemokines were evaluated by using real-time PCR in the liver and spleen and by means of ELISA in plasma. IFN-γ neutralization was achieved by using the anti-IFN-γ antibody XMG1.2 in vivo. RESULTS: Mice with MAS showed a significant upregulation of the IFN-γ pathway, as demonstrated by increased mRNA levels of Ifng and higher levels of phospho-signal transducer and activator of transcription 1 in the liver and spleen and increased expression of the IFN-γ-inducible chemokines Cxcl9 and Cxcl10 in the liver and spleen, as well as in plasma. A marked increase in Il12a and Il12b expression was also found in livers and spleens of mice with MAS. In addition, mice with MAS had a significant increase in numbers of liver CD68+ macrophages. Mice with MAS treated with an anti-IFN-γ antibody showed a significant improvement in survival and body weight recovery associated with a significant amelioration of ferritin, fibrinogen, and alanine aminotransferase levels. In mice with MAS, treatment with the anti-IFN-γ antibody significantly decreased circulating levels of CXCL9, CXCL10, and downstream proinflammatory cytokines. The decrease in CXCL9 and CXCL10 levels paralleled the decrease in serum levels of proinflammatory cytokines and ferritin. CONCLUSION: These results provide evidence for a pathogenic role of IFN-γ in the setting of MAS

    The Role of Staging Laparoscopy for Gastric Cancer Patients: Current Evidence and Future Perspectives

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    A significant proportion of patients diagnosed with gastric cancer is discovered with peritoneal metastases at laparotomy. Despite the continuous improvement in the performance of radiological imaging, the preoperative recognition of such an advanced disease is still challenging during the diagnostic work-up, since the sensitivity of CT scans to peritoneal carcinomatosis is not always adequate. Staging laparoscopy offers the chance to significantly increase the rate of promptly diagnosed peritoneal metastases, thus reducing the number of unnecessary laparotomies and modifying the initial treatment strategy of gastric cancer. The aim of this review was to provide a comprehensive summary of the current literature regarding the role of staging laparoscopy in the management of gastric cancer. Indications, techniques, accuracy, advantages, and limitations of staging laparoscopy and peritoneal cytology were discussed. Furthermore, a focus on current evidence regarding the application of artificial intelligence and image-guided surgery in staging laparoscopy was included in order to provide a picture of the future perspectives of this technique and its integration with modern tools in the preoperative management of gastric cancer

    Gastrointestinal stromal tumors (GISTs) and second malignancies A novel sentinel tumor? A monoinstitutional, STROBE-compliant observational analysis

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    Several evidences showed that patients with gastrointestinal stromal tumors (GISTs) develop additional malignancies. However, thorough incidence of second tumors remains uncertain as the possibility of a common molecular pathogenesis. A retrospective series of 128 patients with histologically proven GIST treated at our institution was evaluated. Molecular analysis of KIT and PDGFR-a genes was performed in all patients. Following the involvement of KRAS mutation in many tumors' pathogenesis, analysis of KRAS was performed in patients with also second neoplasms. Forty-six out of 128 GIST patients (35.9%) had a second neoplasm. Most second tumors (52%) raised from gastrointestinal tract and 19.6% from genitourinary tract. Benign neoplasms were also included (21.7%). Molecular analysis was available for 29/46 patients with a second tumor: wild-type GISTs (n. 5), exon 11 (n. 16), exon 13 (n. 1), exon 9 (n. 1) KIT mutations, exon 14 PDGFR-a mutation (n. 2) and exon 18 PDGFR-a mutation (n. 4). KIT exon 11 mutations were more frequent between patients who developed a second tumor (P=0.0003). Mutational analysis of KRAS showed a wild-type sequence in all cases. In metachronous cases, the median time interval between GIST and second tumor was 21.5 months. The high frequency of second tumors suggests that an unknown common molecular mechanism might play a role, but it is not likely that KRAS is involved in this common pathogenesis. The short interval between GIST diagnosis and the onset of second neoplasms asks for a careful follow-up, particularly in the first 3 years after diagnosis

    Clinical Features, Cardiovascular Risk Profile, and Therapeutic Trajectories of Patients with Type 2 Diabetes Candidate for Oral Semaglutide Therapy in the Italian Specialist Care

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    Introduction: This study aimed to address therapeutic inertia in the management of type 2 diabetes (T2D) by investigating the potential of early treatment with oral semaglutide. Methods: A cross-sectional survey was conducted between October 2021 and April 2022 among specialists treating individuals with T2D. A scientific committee designed a data collection form covering demographics, cardiovascular risk, glucose control metrics, ongoing therapies, and physician judgments on treatment appropriateness. Participants completed anonymous patient questionnaires reflecting routine clinical encounters. The preferred therapeutic regimen for each patient was also identified. Results: The analysis was conducted on 4449 patients initiating oral semaglutide. The population had a relatively short disease duration (42%  60% of patients, and more often than sitagliptin or empagliflozin. Conclusion: The study supports the potential of early implementation of oral semaglutide as a strategy to overcome therapeutic inertia and enhance T2D management

    Prognostic and predictive factors of eribulin efficacy in heavily pretreated patients affected by metastatic breast cancer: correlation with tumor biology and previous therapies

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    Abstract Background: Eribulin mesylate is currently approved in the United States and Europe for the treatment of metastatic breast cancer (MBC). Scope: The objective of this retrospective study is to find specific predictive criteria related to patient or tumor characteristics in order to select patients that might benefit the most from eribulin and define the correct treatment sequence. Findings: Forty-four patients with MBC who received eribulin in third or subsequent lines of therapy in a single Italian center were considered eligible. Patients were stratified by body mass index, hormonal/HER2 status, and previous therapies. Primary endpoint was progression free survival (PFS), whereas secondary endpoint was disease control rate (DCR). A longer PFS was found in patients with hormone-positive tumors (p=0.0051), in HER2-negative cases (p=0.037), and in overweight patients (p=0.0015). No difference in efficacy was observed when eribulin was administered in third or subsequent lines of therapy. Significantly longer PFS (p<0.0001) and higher DCR (p=0.035) were achieved by patients previously treated with paclitaxel-bevacizumab in comparison to those pretreated with other drug combinations or with anthracyclines. Prior treatment with nab-paclitaxel seems to have a detrimental effect on PFS (p=0.0008). Conclusion: Hormone and HER2 status seems a good predictive and prognostic indicator of response to eribulin. Efficacy seems independent from the number of prior therapies, and it is not influenced by prior endocrine treatments and anthracyclines-containing regimens. On the other hand, sensitivity to a prior treatment with paclitaxel-bevacizumab might be predictive of response to eribulin

    Radiologist Checklist for Selecting Patients to Undergo PIPAC (Pressurized IntraPeritoneal Aerosol Chemotherapy)

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    Peritoneal carcinomatosis frequently occurs in advanced gastrointestinal and gynecological cancers. As factors such as poor drug uptake and distribution cause chemotherapy to be less effective, alternative therapies have been explored. Introduced in 2013, PIPAC (pressurized intraperitoneal aerosol chemotherapy) uses aerosolized chemotherapeutics sprayed into the patient’s peritoneal cavity using a laparoscopic approach. Despite the literature showing encouraging data regarding the tolerability and efficacy of PIPAC, there is a lack of articles on the role that imaging plays in selecting patients suitable for PIPAC. The aim of this study is to combine literature-based evidence and clinical experience to provide information able to support training radiologists, as well as experienced radiologists interested in innovative therapies

    From 2000 to 2016: Which Second-Line Treatment in Advanced Non-Small Cell Lung Cancer?

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    New treatments\u2014as immunotherapies and new antiangiogenic agents\u2014are now available in second-line setting for patients affected by EGFR wild-type and ALK-negative non-small-cell lung cancer (NSCLC). Nintedanib, ramucirumab, nivolumab and pembrolizumab have to be included in the therapeutic sequences for patients affected by NSCLC, but no clear selection criteria are to date offered, except for patients with PD-L1 expression 6550\ua0%. Performance status, smoking habits and comorbidities should be considered as clinical criteria in order to select the appropriate treatment, but also tumour characteristics as histotype, platinum resistance and rapid progression after a first-line therapy should be taken into account. The aim of the present paper is to identify subgroups of patients eligible for different therapy sequences

    Safety and Efficacy of a First-Line Chemotherapy Tailored by G8 Score in Elderly Metastatic or Locally Advanced Gastric and Gastro-Esophageal Cancer Patients: A Real-World Analysis

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    Introduction: Gastric (GC) and gastro-esophageal cancer (GEC) are common neoplasms in the elderly. However, in clinical practice, the correct strategy for elderly patients who might benefit from chemotherapy (CT) is unknown. Prospective data are still poor. In this context, we performed a retrospective analysis of GC patients aged &ge;75 years and treated at our institutions. Material and Methods: We retrospectively analyzed 90 patients with confirmed metastatic GC or GEC, treated with an upfront CT. Inclusion criteria were patients aged &ge;75 years, PS 0&ndash;2, normal bone marrow/liver/renal function and no major comorbidities. All patients received a G8 score, and some patients with G8 &le;14 received a comprehensive geriatric assessment (CGA). The primary goal was to perform a safety evaluation based on the incidence of adverse events (AE), and the secondary goal was to determine the efficacy (PFS and OS). The chi-square test and the Kaplan&ndash;Meier method were used to estimate the outcomes. The statistical significance level was set at p &lt; 0.05. Results: Toxicity rates were quite low: G1/G2 (51.1%) and G3/G4 (25.5%). No toxic deaths were reported. The median PFS was 6.21 months and the median OS 11 months. The G8 score and PS ECOG significantly influenced both PFS and OS. A statistically significant correlation among G8, weight loss, hypoalbuminemia and risk of G3/G4 adverse events was also found. Conclusion: Our research on selected elderly patients did not detect broad differences of efficacy and tolerability compared to a young population. Our study, although retrospective and small-sized, showed that G8 score might be an accurate tool to identify elderly GC/GEC patients who could be safely treated with CT, further recognizing patients who could receive a doublet CT and who may require a single agent chemotherapy or a baseline dose reduction
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