Inflammatory profile of induced sputum composition in systemic sclerosis and comparison with healthy volunteers

AbstractSystemic sclerosis (SSc) is a potentially serious and disabling connective tissue disease specially in case of interstitial lung disease (SSc-ILD). The aim of our study was to evaluate the potential utility of dosing in the induced sputum (IS) and to compare their levels in SSc-ILD and SSc-nonILD patients, as well as in healthy volunteers (HV). IS and sera values were also compared. In a prospective cross-sectional analysis, we studied the IS and serum provided from 25 SSc patients, 15 SSc-nonILD and 10 SSc-ILD, compared to 25 HV. We analyzed sputum cell composition and quantified in the supernatant and corresponding serum by commercially available immunoassays: IGFBP-1, IGFBP-2, IGFBP-3, TGF-β, IL-8, TNF-α, YKL-40, MMP-7 and MMP-9. Lung function was studied by the determination of FEV-1 (%), FVC (%), DLCO (%) and KCO (%). The IS of SSc patients had a lower weight than HV (p&lt;0.05, p&lt;0.01) without any significant difference with regard to the cellularity. IGFBP-1 (p &lt; 0.0001), TGF-β (p &lt; 0.05), IL-8 (p &lt; 0.05), YKL-40 (p &lt; 0.0001) and MMP-7 (p &lt; 0.01) levels were increased in the IS of SSc patients compared to HV. Only IL-8 serum levels (p &lt; 0.001) were increased in SSc patients compared to HV. Neither in IS nor in serum were observed differences between SSc-ILD and SSc-nonILD patients. Correlations were observed between IS IL-8 levels and FEV-1 (%) (r =  = − 0.53, p &lt; 0.01), FVC (%) (r = − 0.51, p &lt; 0.01) and annualized ∆KCO (%) (r = 0.57, p &lt; 0.05), between IS TGF-β levels and annualized ∆FEV-1 (%) (r =  = − 0.57, p &lt; 0.05), between IS IGFBP-2 levels and annualized ∆KCO (%) (r = 0.56, p &lt; 0.05). Our study showed that SSc patients exhibit raised IS levels of IGFBP-1, TGF-β, IL-8, YKL-40 and MMP-7, molecules known to be involved in lung remodeling and fibrotic process, without any significant difference between SSc-ILD and SSc-nonILD patients. IL-8, TGF-β and IGFBP-2 are correlated with lung function in SSc patients which emphasize clinical relevance. IS analysis represents a new approach to understand lung inflammatory process in SSc patients. A longitudinal study is needed to evaluate their pathophysiological relevance.</jats:p

Inflammatory profile of induced sputum composition in systemic sclerosis: a comparison with healthy volunteers

AbstractBackgroundSystemic sclerosis (SSc) is a potentially serious and disabling connective tissue disease specially in case of interstitial lung disease (SSc-ILD). The aim of our study was to evaluate the potential utility of dosing in the induced sputum (IS) and to compare their levels in SSc-ILD and SSc-nonILD patients, as well as in healthy volunteers (HV). IS and sera values were also compared.MethodsIn a prospective cross-sectional analysis, we studied the IS and serum provided from 25 SSc patients, 15 SSc-nonILD and 10 SSc-ILD, compared to 25 HV. We analyzed sputum cell composition and quantified in the supernatant and corresponding serum by commercially available immunoassays: IGFBP-1, IGFBP-2, IGFBP-3, TGF-β, IL-8, TNF-α, YKL-40, MMP-7 and MMP-9. Lung function was studied by the determination of FEV-1 (%), FVC (%), DLCO (%) and KCO (%).ResultsThe IS of SSc patients had a lower weight than HV (p&lt;0.01) without any significant difference with regard to the cellularity. IGFBP-1 (p&lt;0.0001), TGF-β (p&lt;0.05), IL-8 (p&lt;0.05), YKL-40 (p&lt;0.0001) and MMP-7 (p&lt;0.01) levels were increased in the IS of SSc patients compared to HV. Only IL-8 serum levels (p&lt;0.001) were increased in SSc patients compared to HV. Neither in IS nor in serum were observed differences between SSc-ILD and SSc-nonILD patients. Correlations were observed between IS IL-8 levels and FEV-1 (%)(r=-0.53, p&lt;0.01), FVC (%) (r=-0.51, p&lt;0.01) and annualized □KCO (%) (r=0.57, p&lt;0.05), between IS TGF-□ levels and annualized □FEV-1 (%) (r=-0.57, p&lt;0.05), between IS IGFBP-2 levels and annualized □KCO (%) (r=0.56, p&lt;0.05).ConclusionOur study showed that SSc patients exhibit raised IS levels of IGFBP-1, TGF-β, IL-8, YKL-40 and MMP-7, molecules known to be involved in lung remodeling and fibrotic process, without any significant difference between SSc-ILD and SSc-nonILD patients. IL-8, TGF-□ and IGFBP-2 are correlated with lung function in SSc patients which emphasize clinical relevance. IS analysis represents a new approach to understand lung inflammatory process in SSc patients. A longitudinal study is needed to evaluate their pathophysiological relevance.</jats:sec

Reproducibility of pulmonary function tests in patients with systemic sclerosis

Abstract Systemic sclerosis (SSc) is a rare autoimmune disease in which interstitial lung disease (ILD) is the leading cause of morbidity and mortality. Clinical management of the lung disease is mainly based on pulmonary function testing (PFT) and their changes over time. Little is known about the reproducibility of PFT testing in SSc patients. The aim of this study was to assess the test–retest reliability and reproducibility of PFTs in SSc patients with or without ILD over 30 days in order determine the potential physiologic variation over the time. We performed prospective observational study of SSc patients. The FVC, FEV1/FVC ratio, DLCO and KCO parameters were assessed in this population at four different timepoints; T0 (time 0) and H3 (T0 + 3 h) defined test–retest reliability, D15 (T0 + 15 days) and D30 (T0 + 30 days) for reproducibility. A mixed linear model was used to test the effect of time (and therefore reproducibility) on patients and we looked for an interaction. We included 25 SSc patients divided in two groups, 14 with ILD and 11 non-ILD. Interactions between time and group were not significant and were not reported. Time and group did not significantly influence the different measures of the PFT: FVC [p values time and group effect respectively (0.33; 0.34)], FEV1/FVC ratio (0.093; 0.056) and DLCO (0.99; 0.13) in the ILD and non ILD group (Table S2). The analyse with interactions between time and group were not significant and are not reported. We also used a Bland Altman test to assess reproducibility for FVC (L) and DLCO (mMKpa/min/L), Figs. 1 and 2 respectively. The measurements were therefore reproducible over time and in each group. PFT parameters are reproducible over time in a clinically stable population of SSc (no significant effect of the time T0, H3, D15 and D30) and there is no significant distinction between patients with ILD and no ILD. These respiratory functional data can further underline their use in clinical practice

Prognostic relevance of high expression of kynurenine pathway markers in glioblastoma

Glioblastoma (GBM) continues to exhibit a discouraging survival rate despite extensive research into new treatments. One factor contributing to its poor prognosis is the tumor's immunosuppressive microenvironment, in which the kynurenine pathway (KP) plays a significant role. This study aimed to explore how KP impacts the survival of newly diagnosed GBM patients. We examined tissue samples from 108 GBM patients to assess the expression levels of key KP markers-tryptophan 2,3-dioxygenase (TDO2), indoleamine 2,3-dioxygenase (IDO1/2), and the aryl hydrocarbon receptor (AhR). Using immunohistochemistry and QuPath software, three tumor cores were analyzed per patient to evaluate KP marker expression. Kaplan-Meier survival analysis and stepwise multivariate Cox regression were used to determine the effect of these markers on patient survival. Results showed that patients with high expression of TDO2, IDO1/2, and AhR had significantly shorter survival times. This finding held true even when controlling for other known prognostic variables, with a hazard ratio of 3.393 for IDO1, 2.775 for IDO2, 1.891 for TDO2, and 1.902 for AhR. We suggest that KP markers could serve as useful tools for patient stratification, potentially guiding future immunomodulating trials and personalized treatment approaches for GBM patients

P14.33 Preoperative Lactate Dehydrogenase levels as a predictor of venous thromboembolism development in glioblastoma patients

Abstract BACKGROUND Venous thromboembolism (VTE) is a common complication in patients with glioblastoma. Despite high incidence of up to 30% per year, concerns about bleeding complications have limited the use of primary anticoagulant prophylaxis. Finding a suitable biomarker to assess the risk of occurrence is therefore of utmost clinical interest. We performed an exploratory study of preoperative routinely used haematological markers as predictor for the development of VTE in glioblastoma patients. MATERIAL AND METHODS Data was retrospectively collected from an existing database of 307 patients diagnosed with glioblastoma by the Oncology Network South-East Netherlands (OnzoZON) between 2006 and 2020. Collected preoperative haematological markers included: haemoglobin, platelets, lactate dehydrogenase, neutrophils, lymphocytes, albumin and derived ratios. In addition, type and date of VTE were retrieved from medical records. Receiver operating curve was used to identify the optimal cut-off values of the preoperative haematological markers. Univariate and multivariate logistic regression analyses were performed to predict VTE for each haematologic marker independently. Variables included in the multivariate analyses were age, gender, type of surgery, Karnofsky performance score, MGMT status, weight, height and BMI, already available from the primary database. RESULTS In the total dataset, 45 patients (15%) suffered from a VTE, most common pulmonary embolism (51%) followed by deep vein thrombosis (31%). Mean time from diagnosis until VTE was 4.3 months (SD = 5.5). Preoperative haemoglobin value was available for analyses in 265 patients, platelets value in 226, lactate dehydrogenase in 98, neutrophils in 133, lymphocytes in 133 and albumin in 56 patients. A preoperative lactate dehydrogenase value &amp;gt; 243 U/L was found to increase the risk of VTE in both univariate and multivariate analysis (P &amp;lt;0.05). Seventeen out of 98 patients of whom lactate dehydrogenase level was available suffered from a VTE, most common pulmonary embolism (59%), followed by deep vein thrombosis (29%) and cerebral venous sinus thrombosis (12%). An elevated lactate dehydrogenase in serum increased the odds for getting a VTE by 3.2 (1.1–9.4). None of the other investigated haematological markers or ratios were found to be significantly correlated with the occurrence of VTE in our study. CONCLUSION Glioblastoma initiates locally haemostatic abnormalities, that propagate systemically though circulating mediators. Our exploratory analysis shows for the first time that preoperative lactate dehydrogenase levels might aid clinicians in identifying patients at risk for a venous thromboembolism. Ultimately this could lead to preventive measures and patient education, but larger and prospective validation of these findings is warranted. </jats:sec

The Use of 18F-FET-PET-MRI in Neuro-Oncology: The Best of Both Worlds—A Narrative Review

Gliomas are the most frequent primary tumors of the brain. They can be divided into grade II-IV astrocytomas and grade II-III oligodendrogliomas, based on their histomolecular profile. The prognosis and treatment is highly dependent on grade and well-identified prognostic and/or predictive molecular markers. Multi-parametric MRI, including diffusion weighted imaging, perfusion, and MR spectroscopy, showed increasing value in the non-invasive characterization of specific molecular subsets of gliomas. Radiolabeled amino-acid analogues, such as 18F-FET, have also been proven valuable in glioma imaging. These tracers not only contribute in the diagnostic process by detecting areas of dedifferentiation in diffuse gliomas, but this technique is also valuable in the follow-up of gliomas, as it can differentiate pseudo-progression from real tumor progression. Since multi-parametric MRI and 18F-FET PET are complementary imaging techniques, there may be a synergistic role for PET-MRI imaging in the neuro-oncological imaging of primary brain tumors. This could be of value for both primary staging, as well as during treatment and follow-up.</jats:p

The Use of 18F-FET-PET-MRI in Neuro-Oncology:The Best of Both Worlds-A Narrative Review

Gliomas are the most frequent primary tumors of the brain. They can be divided into grade II-IV astrocytomas and grade II-III oligodendrogliomas, based on their histomolecular profile. The prognosis and treatment is highly dependent on grade and well-identified prognostic and/or predictive molecular markers. Multi-parametric MRI, including diffusion weighted imaging, perfusion, and MR spectroscopy, showed increasing value in the non-invasive characterization of specific molecular subsets of gliomas. Radiolabeled amino-acid analogues, such as 18F-FET, have also been proven valuable in glioma imaging. These tracers not only contribute in the diagnostic process by detecting areas of dedifferentiation in diffuse gliomas, but this technique is also valuable in the follow-up of gliomas, as it can differentiate pseudo-progression from real tumor progression. Since multi-parametric MRI and 18F-FET PET are complementary imaging techniques, there may be a synergistic role for PET-MRI imaging in the neuro-oncological imaging of primary brain tumors. This could be of value for both primary staging, as well as during treatment and follow-up

The Use of 18F-FET-PET-MRI in Neuro-Oncology: The Best of Both Worlds-A Narrative Review

Gliomas are the most frequent primary tumors of the brain. They can be divided into grade II-IV astrocytomas and grade II-III oligodendrogliomas, based on their histomolecular profile. The prognosis and treatment is highly dependent on grade and well-identified prognostic and/or predictive molecular markers. Multi-parametric MRI, including diffusion weighted imaging, perfusion, and MR spectroscopy, showed increasing value in the non-invasive characterization of specific molecular subsets of gliomas. Radiolabeled amino-acid analogues, such as 18F-FET, have also been proven valuable in glioma imaging. These tracers not only contribute in the diagnostic process by detecting areas of dedifferentiation in diffuse gliomas, but this technique is also valuable in the follow-up of gliomas, as it can differentiate pseudo-progression from real tumor progression. Since multi-parametric MRI and 18F-FET PET are complementary imaging techniques, there may be a synergistic role for PET-MRI imaging in the neuro-oncological imaging of primary brain tumors. This could be of value for both primary staging, as well as during treatment and follow-up