144 research outputs found
Properties of Nanocrystals-formulated Aluminosilicate Bricks
In the present work, seven different types of nanocrystals were studied as additives in the formulation of aluminosilicate bricks. The considered nanocrystals consisted of anatase titanium dioxide (two differently shaped types), boron modified anatase, calcium carbonate (in calcite phase), aluminium hydroxide and silicon carbide (of two diverse sizes), which were prepared using different methods. Syntheses aim to give a good control over a particleâs size and shape. Anatase titania nanocrystals, together with the nano-aluminium hydroxide ones, were synthesized via microwave-assisted procedures, with the use of different additives and without the final calcination steps. The silicon carbide nanoparticles were prepared via laser pyrolysis. The nano-calcium carbonate was prepared via a spray drying technique. All of the nanocrystals were tested as fillers (in 0.5, 1 and 2 wt. % amounts) in a commercial aluminosilicate refractory (55 % Al2O3, 42 % SiO2). They were used to prepare bricks that were thermally treated at 1300 °C for 24 hours, according to the international norms. The differently synthesized nanocrystals were added for the preparation of the bricks, with the aim to improve their heat-insulating and/or mechanical properties. The nanocrystals-modified refractories showed variations in properties, with respect to the untreated aluminosilicate reference in heat-insulating performances (thermal diffusivities were measured by the âhot diskâ technique). In general, they also showed improvements in mechanical compression resistance for all of the samples at 2 wt. %. The best heat insulation was obtained with the addition of nano-aluminium hydroxide at 2 wt. %, while the highest mechanical compression breaking resistance was found with nano-CaCO3 at 2 wt. %. These outcomes were investigated with complementary techniques, like mercury porosimetry for porosity, and Archimedes methods to measure physical properties like the bulk and apparent densities, apparent porosities and water absorption. The results show that the nano-aluminium hydroxide modified bricks were the most porous, which could explain the best heat-insulating performances. There is a less straightforward explanation for the mechanical resistance results, as they may have relations with the characteristics of the pores. Furthermore, the nanoparticles may have possible reactions with the matrix during the heat treatments
Integrated MRIâImmuneâGenomic Features Enclose a Risk Stratification Model in Patients Affected by Glioblastoma
Simple Summary: Despite crucial scientific advances, Glioblastoma (GB) remains a fatal disease with
limited therapeutic options and a lack of suitable biomarkers. The unveiled competence of the brain
immune system together with the breakthrough advent of immunotherapy has shifted the present
translational research on GB towards an immune-focused perspective. Several clinical trials targeting
the immunosuppressive GB background are ongoing. So far, results are inconclusive, underpinning
our partial understanding of the complex cancer-immune interplay in brain tumors. High throughput
Magnetic Resonance (MR) imaging has shown the potential to decipher GB heterogeneity, including
pathologic and genomic clues. However, whether distinct GB immune contextures can be deciphered
at an imaging scale is still elusive, leaving unattained the non-invasive achievement of prognostic
and predictive biomarkers. Along these lines, we integrated genetic, immunopathologic and imaging
features in a series of GB patients. Our results suggest that multiparametric approaches might
offer new efficient risk stratification models, opening the possibility to intercept the critical events
implicated in the dismal prognosis of GB.
Abstract: Background: The aim of the present study was to dissect the clinical outcome of GB patients
through the integration of molecular, immunophenotypic and MR imaging features. Methods: We
enrolled 57 histologically proven and molecularly tested GB patients (5.3% IDH-1 mutant). Two-
Dimensional Free ROI on the Biggest Enhancing Tumoral Diameter (TDFRBETD) acquired by MRI
sequences were used to perform a manual evaluation of multiple quantitative variables, among which
we selected: SD Fluid Attenuated Inversion Recovery (FLAIR), SD and mean Apparent Diffusion
Coefficient (ADC). Characterization of the Tumor Immune Microenvironment (TIME) involved the
immunohistochemical analysis of PD-L1, and number and distribution of CD3+, CD4+, CD8+ Tumor
Infiltrating Lymphocytes (TILs) and CD163+ Tumor Associated Macrophages (TAMs), focusing on
immune-vascular localization. Genetic, MR imaging and TIME descriptors were correlated with
overall survival (OS). Results: MGMT methylation was associated with a significantly prolonged OS
(median OS = 20 months), while no impact of p53 and EGFR status was apparent. GB cases with high
mean ADC at MRI, indicative of low cellularity and soft consistency, exhibited increased OS (median
OS = 24 months). PD-L1 and the overall number of TILs and CD163+TAMs had a marginal impact
on patient outcome. Conversely, the density of vascular-associated (V) CD4+ lymphocytes emerged
as the most significant prognostic factor (median OS = 23 months in V-CD4high vs. 13 months in
V-CD4low, p = 0.015). High V-CD4+TILs also characterized TIME of MGMTmeth GB, while p53mut
appeared to condition a desert immune background. When individual genetic (MGMTunmeth), MR
imaging (mean ADClow) and TIME (V-CD4+TILslow) negative predictors were combined, median OS was 21 months (95% CI, 0â47.37) in patients displaying 0â1 risk factor and 13 months (95% CI
7.22â19.22) in the presence of 2â3 risk factors (p = 0.010, HR = 3.39, 95% CI 1.26â9.09). Conclusion:
Interlacing MRIâimmuneâgenetic features may provide highly significant risk-stratification models
in GB patients
Extracorporeal life support in mitral papillary muscle rupture: Outcome of multicenter study
Background: Post-acute myocardial infarction papillary muscle rupture (post-AMI PMR) may present variable clinical scenarios and degree of emergency due to result of cardiogenic shock. Veno-arterial extracorporeal life support (V-A ECLS) has been proposed to improve extremely poor pre- or postoperative conditions. Information in this respect is scarce.Methods: From the CAUTION (meChanical complicAtion of acUte myocardial infarcTion: an InternatiOnal multiceNter cohort study) database (16 different Centers, data from 2001 to 2018), we extracted adult patients who were surgically treated for post-AMI PMR and underwent pre- or/and postoperative V-A ECLS support. The end-points of this study were in-hospital survival and ECLS complications.Results: From a total of 214 post-AMI PMR patients submitted to surgery, V-A ECLS was instituted in 23 (11%) patients. The median age was 61.7 years (range 46-81 years). Preoperatively, ECLS was commenced in 10 patients (43.5%), whereas intra/postoperative in the remaining 13. The most common V-A ECLS indication was post-cardiotomy shock, followed by preoperative cardiogenic shock and cardiac arrest. The median duration of V-A ECLS was 4 days. V-A ECLS complications occurred in more than half of the patients. Overall, in-hospital mortality was 39.2% (9/23), compared to 22% (42/219) for the non-ECLS group.Conclusions: In post-AMI PMR patients, V-A ECLS was used in almost 10% of the patients either to promote bridge to surgery or as postoperative support. Further investigations are required to better evaluate a potential for increased use and its effects of V-A ECLS in such a context based on the still high perioperative mortality
Epidermal Growth Factor Receptor (EGFR) mutation analysis, gene expression profiling and EGFR protein expression in primary prostate cancer
<p>Abstract</p> <p>Background</p> <p>Activating mutations of the epidermal growth factor receptor (<it>EGFR</it>) confer sensitivity to the tyrosine kinase inhibitors (TKi), gefitinib and erlotinib. We analysed EGFR expression, EGFR mutation status and gene expression profiles of prostate cancer (PC) to supply a rationale for EGFR targeted therapies in this disease.</p> <p>Methods</p> <p>Mutational analysis of EGFR TK domain (exons from 18 to 21) and immunohistochemistry for EGFR were performed on tumour tissues derived from radical prostatectomy from 100 PC patients. Gene expression profiling using oligo-microarrays was also carried out in 51 of the PC samples.</p> <p>Results</p> <p>EGFR protein overexpression (EGFR<sub>high</sub>) was found in 36% of the tumour samples, and mutations were found in 13% of samples. Patients with EGFR<sub>high </sub>tumours experienced a significantly increased risk of biochemical relapse (hazard ratio-HR 2.52, p=0.02) compared with patients with tumours expressing low levels of EGFR (EGFR<sub>low</sub>). Microarray analysis did not reveal any differences in gene expression between EGFR<sub>high </sub>and EGFR<sub>low </sub>tumours. Conversely, in EGFR<sub>high </sub>tumours, we were able to identify a 79 gene signature distinguishing mutated from non-mutated tumours. Additionally, 29 genes were found to be differentially expressed between mutated/EGFR<sub>high </sub>(n=3) and mutated/EGFR<sub>low </sub>tumours (n=5). Four of the down-regulated genes, U19/EAF2, ABCC4, KLK3 and ANXA3 and one of the up-regulated genes, FOXC1, are involved in PC progression.</p> <p>Conclusions</p> <p>Based on our findings, we hypothesize that accurate definition of the EGFR status could improve prognostic stratification and we suggest a possible role for EGFR-directed therapies in PC patients. Having been generated in a relatively small sample of patients, our results warrant confirmation in larger series.</p
Off-label long acting injectable antipsychotics in real-world clinical practice: a cross-sectional analysis of prescriptive patterns from the STAR Network DEPOT study
Introduction Information on the off-label use of Long-Acting Injectable (LAI) antipsychotics in the real world is lacking. In this study, we aimed to identify the sociodemographic and clinical features of patients treated with on- vs off-label LAIs and predictors of off-label First- or Second-Generation Antipsychotic (FGA vs. SGA) LAI choice in everyday clinical practice. Method In a naturalistic national cohort of 449 patients who initiated LAI treatment in the STAR Network Depot Study, two groups were identified based on off- or on-label prescriptions. A multivariate logistic regression analysis was used to test several clinically relevant variables and identify those associated with the choice of FGA vs SGA prescription in the off-label group. Results SGA LAIs were more commonly prescribed in everyday practice, without significant differences in their on- and off-label use. Approximately 1 in 4 patients received an off-label prescription. In the off-label group, the most frequent diagnoses were bipolar disorder (67.5%) or any personality disorder (23.7%). FGA vs SGA LAI choice was significantly associated with BPRS thought disorder (OR = 1.22, CI95% 1.04 to 1.43, p = 0.015) and hostility/suspiciousness (OR = 0.83, CI95% 0.71 to 0.97, p = 0.017) dimensions. The likelihood of receiving an SGA LAI grew steadily with the increase of the BPRS thought disturbance score. Conversely, a preference towards prescribing an FGA was observed with higher scores at the BPRS hostility/suspiciousness subscale. Conclusion Our study is the first to identify predictors of FGA vs SGA choice in patients treated with off-label LAI antipsychotics. Demographic characteristics, i.e. age, sex, and substance/alcohol use co-morbidities did not appear to influence the choice towards FGAs or SGAs. Despite a lack of evidence, clinicians tend to favour FGA over SGA LAIs in bipolar or personality disorder patients with relevant hostility. Further research is needed to evaluate treatment adherence and clinical effectiveness of these prescriptive patterns
Effectiveness of lithium in subjects with treatment-resistant depression and suicide risk: results and lessons of an underpowered randomised clinical trial
BACKGROUND: As lithium treatment might be effective in reducing the risk of deliberate self-harm (DSH) in adult patients with unipolar affective disorders, we designed a pragmatic randomised trial to assess its efficacy in more than 200 patients with treatment-resistant depression. However, we randomised 56 patients only. The aim of this report is therefore twofold: first, to disseminate the results of this underpowered study which may be incorporated into future meta-analytical reviews; second, to analyse some critical aspects of the study which might explain failure to reach the target sample size.METHODS: We carried out a randomised, parallel group, assessor-blinded superiority clinical trial. Adults with a diagnosis of major depression, an episode of DSH in the previous 12 months and inadequate response to at least two antidepressants given sequentially at an adequate dose for an adequate time for the current depressive episode were allocated to add lithium to usual care (intervention arm) versus usual care alone (control arm). Suicide completion and acts of DSH during the 12 months of follow-up constituted the composite primary outcome.RESULTS: Of 58 patients screened for inclusion, 29 were allocated to lithium plus usual care and 27 were assigned to usual care without lithium. Six patients in the lithium plus usual care group and seven in the usual care group committed acts of DSH during the follow-up phase. The survival probability did not differ between the two treatment arms (Chi2 = 0.17, p =0.676). With regard to changes in the severity of depressive symptomatology from baseline to endpoint, no significant differences were detected.CONCLUSIONS: The present study failed to achieve the minimum sample size needed to detect a clinically meaningful difference between the two treatment arms. Consequently, the finding that lithium, in addition to usual care, did not exert a positive effect in terms of reduction of DSH after 12 months of follow-up is likely due to the lack of sufficient statistical power to detect a difference, if a difference existed. The dissemination of the results of this underpowered study will inform future meta-analytical reviews on lithium and suicide-related outcomes.TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00927550
Colorectal Cancer Stage at Diagnosis Before vs During the COVID-19 Pandemic in Italy
IMPORTANCE Delays in screening programs and the reluctance of patients to seek medical
attention because of the outbreak of SARS-CoV-2 could be associated with the risk of more advanced
colorectal cancers at diagnosis.
OBJECTIVE To evaluate whether the SARS-CoV-2 pandemic was associated with more advanced
oncologic stage and change in clinical presentation for patients with colorectal cancer.
DESIGN, SETTING, AND PARTICIPANTS This retrospective, multicenter cohort study included all
17 938 adult patients who underwent surgery for colorectal cancer from March 1, 2020, to December
31, 2021 (pandemic period), and from January 1, 2018, to February 29, 2020 (prepandemic period),
in 81 participating centers in Italy, including tertiary centers and community hospitals. Follow-up was
30 days from surgery.
EXPOSURES Any type of surgical procedure for colorectal cancer, including explorative surgery,
palliative procedures, and atypical or segmental resections.
MAIN OUTCOMES AND MEASURES The primary outcome was advanced stage of colorectal cancer
at diagnosis. Secondary outcomes were distant metastasis, T4 stage, aggressive biology (defined as
cancer with at least 1 of the following characteristics: signet ring cells, mucinous tumor, budding,
lymphovascular invasion, perineural invasion, and lymphangitis), stenotic lesion, emergency surgery,
and palliative surgery. The independent association between the pandemic period and the outcomes
was assessed using multivariate random-effects logistic regression, with hospital as the cluster
variable.
RESULTS A total of 17 938 patients (10 007 men [55.8%]; mean [SD] age, 70.6 [12.2] years)
underwent surgery for colorectal cancer: 7796 (43.5%) during the pandemic period and 10 142
(56.5%) during the prepandemic period. Logistic regression indicated that the pandemic period was
significantly associated with an increased rate of advanced-stage colorectal cancer (odds ratio [OR],
1.07; 95%CI, 1.01-1.13; P = .03), aggressive biology (OR, 1.32; 95%CI, 1.15-1.53; P < .001), and stenotic
lesions (OR, 1.15; 95%CI, 1.01-1.31; P = .03).
CONCLUSIONS AND RELEVANCE This cohort study suggests a significant association between the
SARS-CoV-2 pandemic and the risk of a more advanced oncologic stage at diagnosis among patients
undergoing surgery for colorectal cancer and might indicate a potential reduction of survival for
these patients
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