Real world data in the era of Immune Checkpoint Inhibitors (ICIs): Increasing evidence and future applications in lung cancer.

Immune checkpoint inhibitors (ICIs) targeting programmed death 1 (PD-1) and PD-ligand 1 (PD-L1) quickly subverted the standard of treatment in Non-Small Cell Lung Cancer (NSCLC), where they were first introduced in all comers previously treated advanced/metastatic NSCLC patients and subsequently in the first line of PD-L1 selected cases of metastatic and locally advanced disease. Treatment algorithm is an evolving landscape, where the introduction of front-line ICIs, with or without chemotherapy, unavoidably influences the following treatment lines. In this context, medical oncologists are currently facing many unclear issues, which have been not clarified so far by available data. Effectiveness and safety in special populations underrepresented in clinical trials - such as elderly, poor PS, hepatitis or human immunodeficiency virus-affected patients - are only a part of the unexplored side of ICIs in the real world. Indeed, pivotal randomized clinical trials (RCTs) often lack of external validity because eligibility criteria exclude some patient subgroups commonly treated in real-world clinical practice. Similarly, cost-effectiveness and sustainability of these innovative agents are important issues to be considered in the real-world. Though affected by several limitations, real-world evidence (RWE) studies allow to collect data regarding overall treated patients in clinical practice according to local authority regulations, overcoming the intrinsic limits of RCTs. The present review focuses on RWE about ICIs in lung cancer treatment, with particular reference to special patient populations, and discusses potential application of real-world data in a potential innovative drug development model

Immune-related adverse events (irAEs) in advanced non-small cell lung cancer (aNSCLC): Platelet-to-lymphocyte ratio (PLR) predicts the risk of development and relapse

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Comparison between adenosine triphosphate bioluminescence and aerobic colony count to assess surface sanitation in the hospital environment

Background: Adenosine triphosphate bioluminescence produced by the firefly luciferase has been successfullyintroduced to verify cleaning procedures in the food industry according to the Hazard Analysis Critical Control Pointprogram.Our aim was to evaluate the reliability of bioluminescence as a tool to monitor the effectiveness of sanitation in healthcaresettings, in comparison with the microbiological gold standard.Methods: 614 surfaces of various material were randomly sampled in Policlinico University Hospital units in Palermo,Italy, to detect adenosine triphosphate bioluminescence and aerobic colony count. Linear regression model andPearson correlation coefficient were used to estimate the relationship between the two variables of the study.Results: Aerobic colony count median was 1.71 colony forming units/cm2 (interquartile range = 3.8), whereasadenosine triphosphate median was 59.9 relative light units/cm2 (interquartile range = 128.3). Pearson coefficientR2 was 0.09. Sensitivity and specificity of bioluminescence test with respect to microbiology were 46% and 71%,whereas positive predictive value and negative predictive value were 53% and 65%, respectively.Conclusion: According to our results, there seemed to be no linear correlation between aerobic colony countand adenosine triphosphate values, suggesting that current bioluminescence technology has not any proportionalrelationships with culturable microbes contaminating environmental surfaces in health-care settings

Sex-based heterogeneity in non-small cell lung cancer (NSCLC) and response to immune checkpoint inhibitors (ICIs): a narrative review

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Detection of circulating immunosuppressive cytokines in malignant pleural mesothelioma patients for prognostic stratification.

Abstract Background No data on circulating biomarkers for the prognostic stratification of Malignant Pleural Mesothelioma (MPM) patients are available. We prospectively explored the prognostic role of circulating monocyte and cytokine levels and their dynamic change during chemotherapy. Patients and Methods MPM patients receiving a first line treatment based on a platinum compound plus pemetrexed were eligible. Blood samples were collected at the baseline and at the end of induction chemotherapy. CCL-2, IL-10 and TGF-β levels in plasma were quantified by Enzyme-Linked Immunosorbent Assay (ELISA); white blood cells, monocytes and platelets were evaluated by blood count test. Results Thirty-one patients were included in the study. Median overall survival (OS) was 12.13 months versus 9.6 months in patients with lower and higher monocytes count, respectively (p value = 0.02). We further stratified patients according to a combined score based on the association of IL-10, TGF-β levels and monocytes count. High combined score was associated with shorter OS and PFS in univariate and multivariate analysis. Chemotherapy induced an increase in monocytes, IL-10, but not TGF-β levels. Conclusion The prognostic value of circulating levels of multiple immunosuppressive cytokines and inflammatory cells should be confirmed in a wider validation set of MPM patients

Impaired Cerebral Haemodynamics in Vascular Depression: Insights From Transcranial Doppler Ultrasonography

Introduction: Late-life depression is a well-known risk factor for future dementia. Increasing evidences also show a link between cerebral hypoperfusion and neurodegeneration, although data on Transcranial Doppler ultrasonography (TCD)-derived measures in patients with “Vascular Depression” (VD) are lacking. The aim of this study was to assess and correlate TCD parameters with cognitive function and severity of subcortical ischemic vascular disease in a sample of VD patients.Methods: Seventy six patients (mean age 72.5 ± 5.3 years; 53.9% females) met the DSM-5 diagnostic criteria for unipolar major depression. Mean blood flow velocity (MBFv) and pulsatility index (PI) were recorded from the middle cerebral artery. Quantification of depressive symptoms (17-item Hamilton Depression Rating Scale –HDRS), neuropsychological test evaluating frontal lobe abilities (Stroop Color-Word test interference—Stroop T), and white matter lesions (WMLs) load according to the Fazekas visual score were also assessed.Results: WMLs severity was mild in 20 patients (group I), moderate in 32 (group II), and severe in 24 (group III). The groups were comparable in terms of clinical features, vascular risk factors profile, and HDRS score, whereas Stroop T score was worse in group III. An increased PI and a reduced MBFv were found in VD patients with severe WMLs. According to the regression analysis, a reduced MBFv was independently and significantly associated with depressive symptoms and executive dysfunction, even after adjusting for demographic features and vascular risk factors. Similarly, an independent and significant association was observed between the increase of PI and both Stroop T and WMLs severity.Conclusions: A TCD profile of low perfusion and high vascular resistance in VD patients suggests a diffuse cerebrovascular pathology likely arising from the small vessels and then extending to larger arteries. Hemodynamic dysfunction might play a pathogenic role in the development of cognitive impairment in patients with late-life depression and subcortical ischemic vascular disease. TCD represents a valuable tool in the early detection, assessment, and management of VD patients at risk for dementia

Fluid escape structures revealing volcanic and tectonic activity in the Graham Bank (Sicily Channel)

The Graham Bank (NW Sicily Channel, Central Mediterranean) is characterised by a complex seafloor morphology, where morphostructural highs, submarine plain, escarpments, and negative and positive relieves indicate a complex structural setting and the occurrence of seepage fluids. New high-resolution acoustic data (multibeam, Chirp profiles) and multi-channel profiles, allowed us to differentiate two main morphological sectors, and to identify several pockmarks and mounds linked to fluid escape phenomena. The eastern sector, corresponding to the volcanic edifices of the Graham Bank, is characterised by volcanic context with rough morphology, several mounds, focused seepage plumes and magmatic acoustic substrate, all related to the activity forming both the Graham Bank and the new volcanic cones here identified. The western sector displays a generally flat morphology dominated by Late Pleistocene-Holocene outer shelf deposits, where mounds and pockmarks with sub-circular and ellipsoidal shapes, V- to U-shaped in cross-section, are the prevailing features indicating the migration of fluids to the seafloor. These two areas are separated by a vertical deep fault forming a deeply incised channel with NW-SE direction. The latter is bordered by steep walls forming fault escarpments, which shed the eroded materials to the adjacent lower slope and deep-water zones. The overall morphostructural setting suggests a tectonic control in the morphological conformation of the seabed and in the distribution of both pockmarks and mounds. The aligned mounds have both NW-SE and NNW-SSE orientation, sometimes extending several hundred metres and forming hummocky surfaces. The aligned pockmarks are strictly comparable to the orientation of the faults related to the most recent tectonic activity. The good correlation between fluid escape structures and the main fault systems involving the kilometric sedimentary cover suggests that the degassing of fluids is rooted in depth revealing that extensional tectonics acts with very deep subvertical recent faults developing along and reactivating the Cenozoic (both Plio-Quaternary and Messinian) and Mesozoic tectonic systems.peer-reviewe

Real-world impact of the introduction of chemo-immunotherapy in extended small cell lung cancer: a multicentric analysis

BackgroundRecent clinical trials demonstrated longer survival in extended small cell lung cancer (SCLC) patients treated with immunotherapy in addition to chemotherapy. However, the magnitude of benefit is modest and the impact in real-world setting has to be fully established.MethodsWe collected clinical data and radiological imaging of patients affected by extended or relapsing SCLC and consecutively treated according to clinical practice between 2016 and 2023. As primary end-point, we compared pre-defined outcome indicators before and after the introduction of chemo-immunotherapy (May 2020): 6-month and 12-month progression free survival (PFS) rate, 12-month and 18-month overall survival (OS). Among those who were treated after May 2020, patients who did not receive immunotherapy according to treating physician’s choice were included in the analysis to minimize clinical selection bias.ResultsThe analysis included 214 patients: 132 (61.7%) were treated in an Academic cancer center and 82 (38.3%) in two community hospitals; 104 were treated before May 2020. Median PFS of the overall study population was 4.8 months (95% confidence interval [95% CI]: 4.4-5.4), median OS was 7.1 months (95% CI: 6.3-7.7). Estimated PFS and OS were significantly longer in patients treated after May 2020 with hazard ratio (HR) for PFS and OS of 0.61 (95% CI: 0.46-0.81, p < 0.001) and 0.70 (95% CI: 0.52-0.93, p = 0.015), respectively. 6-month PFS rate increased from 27% to 40% (p = 0.04) while 12-months PFS raised from 1% to 11% (p = 0.003). 12-month and 18-month OS rate increased from 15% to 28% (p = 0.03) and from 2.1% to 12% (p = 0.009), respectively. After May 2020 the median number of hospitalization days per patient decreased significantly and the incidence of severe AEs was similar. Among patients treated with chemo-immunotherapy, the onset of immune-related AEs was associated with improved PFS and OS (HR 0.55, 95% CI: 0.35-0.89, p = 0.012 and HR 0.47, 95%CI 0.28-0.77, p = 0.002, respectively).ConclusionsThe real-world analysis shows a meaningful improvement of outcome indicators after the introduction of chemo-immunotherapy, with reduction of the duration of hospitalization, thus supporting the use of chemo-immunotherapy and the need for further biomarker research