Publications by authors named "Marco Salvatore"

376 Publications

The impact of different preanalytical methods related to CA 15-3 determination in frozen human blood samples: a systematic review.

Syst Rev 2021 Apr 9;10(1):102. Epub 2021 Apr 9.

IRCCS SDN, Via E. Gianturco, 80143, Naples, Italy.

Background: The determination of CA 15-3 is useful for monitoring breast cancer patients. Several retrospective studies determined CA 15-3 levels in frozen samples to evaluate the sensitivity and specificity of novel biomarkers in relation to breast cancer; however, freeze-thaw cycles, as well as preanalytical variables before sample storage, are not always reported. Here, we analyzed the current scientific literature to identify possible critical aspects related to CA 15-3 determination in frozen-stored human serum/plasma samples.

Methods: We obtained data from 4 different bibliographic databases: Web of Science, Embase, PubMed, and Cochrane Library. We followed the PRISMA guidelines to screen and select the eligible articles discussed in the final revision.

Results: Initially, 674 scientific papers were evaluated, and after the application of the screening and eligibility criteria, 18 studies were included in the qualitative synthesis. The analysis reported an important level of heterogeneity concerning the preanalytical phase before sample storage.

Conclusion: Although advances in healthcare have been achieved using certified workflows in medical diagnostics, standardized preanalytical processes are not always applied when referring to frozen-stored biosamples. Biobanks will guarantee the best possible conditions for the storage of human biological samples to be used in clinical research. The use of certified bioresources will favor the optimal development and introduction of new disease biomarkers.
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http://dx.doi.org/10.1186/s13643-021-01631-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8033739PMC
April 2021

Giant Epidermoid Cyst of Posterior Fossa-Our Experience and Literature Review.

Dose Response 2021 Jan-Mar;19(1):15593258211002061. Epub 2021 Mar 24.

Otosurgery Unit, ULSS2, Treviso Hospital, Treviso, Italy.

Introduction: Intracranial epidermoid cysts are the most frequent congenital intracranial lesion. They rare and benign tumors that can present in different clinical situations depending on location and extension of the disease. Diagnosis is obtained with radiological imaging with RM and non-enhanced TC as elective investigating methods. Elective treatment is surgery, based on total/subtotal excision sparring healthy neurovascular structures, considering the benign nature of this lesion.

Case Report: In this study we present the case of a 79-year-old woman affected by recidivist epidermal cyst of the posterior fossa. Clinical presentation was characterized by positional subjective vertigo, intense headache localized in the right part of the head increased by Valsalva maneuver and retroarticular subcutaneous swelling. Radiological investigation found a giant epidemoid cyst of the posterior fossa (8,4 x 4,8 x 5,8 cm), treated with surgery. In the postoperative, the patient was fine and no neurological deficit has been encounterd.

Review: In this study, we present a review of the literature regarding giant epidermoid cysts of posterior fossa. Only 11 cases were reported before ours, which actually is one of the largest ever described.
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http://dx.doi.org/10.1177/15593258211002061DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7995313PMC
March 2021

Evaluation of the Diagnostic Performance of Positron Emission Tomography/Magnetic Resonance for the Diagnosis of Liver Metastases.

Invest Radiol 2021 Mar 25. Epub 2021 Mar 25.

From The Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Charlestown, and Department of Radiology, Xinhua Hospital, affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China Department of Radiology, Division of Abdominal Imaging, Massachusetts General Hospital, Boston IRCCS, Department of Radiology, The Institute for Hospitalization and Healthcare (IRCCS) SDN, Napoli, Italy Division of Nuclear Medicine, Department of Radiology, Faculdade de Ciências Médicas, Universidade Estadual de Campinas (Unicamp), Campinas, São Paulo, Brazil The Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston Department of Surgery, Massachusetts General Hospital, Boston Department of Medicine, Massachusetts General Hospital, Boston The Institute for Hospitalization and Healthcare (IRCCS) SDN, Napoli, Italy Department of Radiology and Nuclear Medicine, University Suor Orsola Benincasa and SDN IRCCS, Napoli, Italy Department of Radiology and Nuclear Medicine, Assuta Medical Center and School of Medicine, Tel Aviv University, TLV, Israel Department of Nuclear Medicine, The Chaim Sheba Medical Center Tel Hashomer Israel Departamento de Medicina Nuclear, HM Hospitales, Madrid, Spain Institute of Diagnostic and Interventional Radiology, University Hospital Essen, University Duisburg-Essen, Essen, Germany Department of Radiology and Nuclear Medicine, Massachusetts General Hospital, Boston, MA.

Objective: The aim of this study was to compare the performance of positron emission tomography (PET)/magnetic resonance (MR) versus stand-alone PET and stand-alone magnetic resonance imaging (MRI) in the detection and characterization of suspected liver metastases.

Materials And Methods: This multi-institutional retrospective performance study was approved by the institutional review boards and was Health Insurance Portability and Accountability Act compliant, with waiver of informed consent. Seventy-nine patients with confirmed solid extrahepatic malignancies who underwent upper abdominal PET/MR between February 2017 and June 2018 were included. Where focal hepatic lesions were identified, the likelihood of a diagnosis of a liver metastasis was defined on an ordinal scale for MRI, PET, and PET/MRI by 3 readers: 1 nuclear medicine physician and 2 radiologists. The number of lesions per patient, lesion size, and involved hepatic segments were recorded. Proof of metastases was based on histopathologic correlation or clinical/imaging follow-up. Diagnostic performance was assessed using sensitivity, specificity, positive and negative predictive values, and receiver operator characteristic curve analysis.

Results: A total of 79 patients (53 years, interquartile range, 50-68; 43 men) were included. PET/MR had a sensitivity of 95%, specificity of 97%, positive predictive value of 97%, and negative predictive value of 95%. The sensitivity, specificity, positive predictive value, and negative predictive value of MRI were 88%, 98%, 98%, and 90% and for PET were 83%, 97%, 97%, and 86%, respectively. The areas under the curve for PET/MRI, MRI, and PET were 95%, 92%, and 92%, respectively.

Conclusions: Contrast-enhanced PET/MR has a higher sensitivity and negative predictive value than either PET or MRI alone in the setting of suspected liver metastases. Fewer lesions were characterized as indeterminate by PET/MR in comparison with PET and MRI. This superior performance could potentially impact treatment and management decisions for patients with suspected liver metastases.
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http://dx.doi.org/10.1097/RLI.0000000000000782DOI Listing
March 2021

Antifouling Strategies of Nanoparticles for Diagnostic and Therapeutic Application: A Systematic Review of the Literature.

Nanomaterials (Basel) 2021 Mar 18;11(3). Epub 2021 Mar 18.

IRCCS SDN-Via E. Gianturco 113, 80143 Naples, Italy.

Nanoparticles (NPs) are promising platforms for the development of diagnostic and therapeutic tools. One of the main hurdle to their medical application and translation into the clinic is the fact that they accumulate in the spleen and liver due to opsonization and scavenging by the mononuclear phagocyte system. The "protein corona" controls the fate of NPs in vivo and becomes the interface with cells, influencing their physiological response like cellular uptake and targeting efficiency. For these reasons, the surface properties play a pivotal role in fouling and antifouling behavior of particles. Therefore, surface engineering of the nanocarriers is an extremely important issue for the design of useful diagnostic and therapeutic systems. In recent decades, a huge number of studies have proposed and developed different strategies to improve antifouling features and produce NPs as safe and performing as possible. However, it is not always easy to compare the various approaches and understand their advantages and disadvantages in terms of interaction with biological systems. Here, we propose a systematic study of literature with the aim of summarizing current knowledge on promising antifouling coatings to render NPs more biocompatible and performing for diagnostic and therapeutic purposes. Thirty-nine studies from 2009 were included and investigated. Our findings have shown that two main classes of non-fouling materials (i.e., pegylated and zwitterionic) are associated with NPs and their applications are discussed here highlighting pitfalls and challenges to develop biocompatible tools for diagnostic and therapeutic uses. In conclusion, although the complexity of biofouling strategies and the field is still young, the collective data selected in this review indicate that a careful tuning of surface moieties is a pivotal step to lead NPs through their future clinical applications.
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http://dx.doi.org/10.3390/nano11030780DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8003124PMC
March 2021

Radiomic and Genomic Machine Learning Method Performance for Prostate Cancer Diagnosis: Systematic Literature Review.

J Med Internet Res 2021 Apr 1;23(4):e22394. Epub 2021 Apr 1.

IRCCS SDN, Naples, Italy.

Background: Machine learning algorithms have been drawing attention at the joining of pathology and radiology in prostate cancer research. However, due to their algorithmic learning complexity and the variability of their architecture, there is an ongoing need to analyze their performance.

Objective: This study assesses the source of heterogeneity and the performance of machine learning applied to radiomic, genomic, and clinical biomarkers for the diagnosis of prostate cancer. One research focus of this study was on clearly identifying problems and issues related to the implementation of machine learning in clinical studies.

Methods: Following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) protocol, 816 titles were identified from the PubMed, Scopus, and OvidSP databases. Studies that used machine learning to detect prostate cancer and provided performance measures were included in our analysis. The quality of the eligible studies was assessed using the QUADAS-2 (quality assessment of diagnostic accuracy studies-version 2) tool. The hierarchical multivariate model was applied to the pooled data in a meta-analysis. To investigate the heterogeneity among studies, I statistics were performed along with visual evaluation of coupled forest plots. Due to the internal heterogeneity among machine learning algorithms, subgroup analysis was carried out to investigate the diagnostic capability of machine learning systems in clinical practice.

Results: In the final analysis, 37 studies were included, of which 29 entered the meta-analysis pooling. The analysis of machine learning methods to detect prostate cancer reveals the limited usage of the methods and the lack of standards that hinder the implementation of machine learning in clinical applications.

Conclusions: The performance of machine learning for diagnosis of prostate cancer was considered satisfactory for several studies investigating the multiparametric magnetic resonance imaging and urine biomarkers; however, given the limitations indicated in our study, further studies are warranted to extend the potential use of machine learning to clinical settings. Recommendations on the use of machine learning techniques were also provided to help researchers to design robust studies to facilitate evidence generation from the use of radiomic and genomic biomarkers.
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http://dx.doi.org/10.2196/22394DOI Listing
April 2021

The relationship between cardiac injury, inflammation and coagulation in predicting COVID-19 outcome.

Sci Rep 2021 03 22;11(1):6515. Epub 2021 Mar 22.

Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.

High sensitivity troponin T (hsTnT) is a strong predictor of adverse outcome during SARS-CoV-2 infection. However, its determinants remain partially unknown. We aimed to assess the relationship between severity of inflammatory response/coagulation abnormalities and hsTnT in Coronavirus Disease 2019 (COVID-19). We then explored the relevance of these pathways in defining mortality and complications risk and the potential effects of the treatments to attenuate such risk. In this single-center, prospective, observational study we enrolled 266 consecutive patients hospitalized for SARS-CoV-2 pneumonia. Primary endpoint was in-hospital COVID-19 mortality. hsTnT, even after adjustment for confounders, was associated with mortality. D-dimer and CRP presented stronger associations with hsTnT than PaO. Changes of hsTnT, D-dimer and CRP were related; but only D-dimer was associated with mortality. Moreover, low molecular weight heparin showed attenuation of the mortality in the whole population, particularly in subjects with higher hsTnT. D-dimer possessed a strong relationship with hsTnT and mortality. Anticoagulation treatment showed greater benefits with regard to mortality. These findings suggest a major role of SARS-CoV-2 coagulopathy in hsTnT elevation and its related mortality in COVID-19. A better understanding of the mechanisms related to COVID-19 might pave the way to therapy tailoring in these high-risk individuals.
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http://dx.doi.org/10.1038/s41598-021-85646-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7985490PMC
March 2021

The Diagnosis of Cystic Fibrosis in Adult Age. Data from the Italian Registry.

Diagnostics (Basel) 2021 Feb 16;11(2). Epub 2021 Feb 16.

Italian Cystic Fibrosis Registry, 00162 Rome, Italy.

Cystic Fibrosis (CF) registries are an essential resource of epidemiological and clinical data. Although the median age at diagnosis is usually reported in the first months of life, a minority of individuals is diagnosed during adulthood. The aim of this study was to describe demographic, genetic, and clinical characteristics of this subgroup of the Italian CF population by using data from the Italian CF Registry (ICFR). Patients ≥18 years at diagnosis were selected and clinical data at diagnosis were analyzed from the 2012-2018 ICFR data (Cohort A). Subjects with diagnosis ≥18 years were selected from 2018 ICFR dataset (Cohort B) to describe their clinical status. In 2012-18 the incidence of late diagnosis was 18.2%, whereas, in 2018, the prevalence of patients diagnosed ≥18 years was 12.54%. The median age of late diagnosis was 36.2 years, ranging from 19.0 to 68.3. The male patients were diagnosed because of infertility in the 45.9% of cases. Median sweat chloride value (SCL) was 69 mmol/L (range 9-150). mutation accounted for 28.3% of alleles. A wide variability in respiratory function was present with a median percent predicted Forced Expiratory Volume in the first second (ppFEV) of 90.8% (range 20-147%). Low prevalence of pancreatic insufficiency (25%) and of () infection (17%) suggest a mild CF phenotype in the majority of patients. The assessment of the clinical status in the 2018 dataset and the comparison between genders showed a greater nutritional and respiratory impairment in females. Further studies are needed to clarify the importance of a true diagnostic delay or of late onset of CF symptoms.
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http://dx.doi.org/10.3390/diagnostics11020321DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7920411PMC
February 2021

An international expert opinion statement on the utility of PET/MR for imaging of skeletal metastases.

Eur J Nucl Med Mol Imaging 2021 Feb 22. Epub 2021 Feb 22.

Department of Radiology, Massachusetts General Hospital, Boston, MA, USA.

Background: MR is an important imaging modality for evaluating musculoskeletal malignancies owing to its high soft tissue contrast and its ability to acquire multiparametric information. PET provides quantitative molecular and physiologic information and is a critical tool in the diagnosis and staging of several malignancies. PET/MR, which can take advantage of its constituent modalities, is uniquely suited for evaluating skeletal metastases. We reviewed the current evidence of PET/MR in assessing for skeletal metastases and provided recommendations for its use.

Methods: We searched for the peer reviewed literature related to the usage of PET/MR in the settings of osseous metastases. In addition, expert opinions, practices, and protocols of major research institutions performing research on PET/MR of skeletal metastases were considered.

Results: Peer-reviewed published literature was included. Nuclear medicine and radiology experts, including those from 13 major PET/MR centers, shared the gained expertise on PET/MR use for evaluating skeletal metastases and contributed to a consensus expert opinion statement. [18F]-FDG and non [18F]-FDG PET/MR may provide key advantages over PET/CT in the evaluation for osseous metastases in several primary malignancies.

Conclusion: PET/MR should be considered for staging of malignancies where there is a high likelihood of osseous metastatic disease based on the characteristics of the primary malignancy, hight clinical suspicious and in case, where the presence of osseous metastases will have an impact on patient management. Appropriate choice of tumor-specific radiopharmaceuticals, as well as stringent adherence to PET and MR protocols, should be employed.
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http://dx.doi.org/10.1007/s00259-021-05198-2DOI Listing
February 2021

Prognostic value of 18F-FDG PET/MRI in patients with advanced oropharyngeal and hypopharyngeal squamous cell carcinoma.

Ann Nucl Med 2021 Apr 11;35(4):479-484. Epub 2021 Feb 11.

IRCCS SDN, Naples, Italy.

Objective: The aim of this study was to evaluate the prognostic value of combined positron emission tomography (PET)/magnetic resonance imaging (MRI) parameters provided by simultaneous 18F-fluorodeoxyglucose (FDG) PET/MRI in patients with locally advanced oropharyngeal and hypopharyngeal squamous cell carcinomas (OHSCC).

Methods: Forty-five patients with locally advanced OHSCC who underwent simultaneous FDG PET/MRI before (chemo)radiotherapy were retrospectively enrolled. Peak standardized uptake value (SULpeak), metabolic tumor volume (MTV) and total lesion glycolysis (TLG) of the primary lesion were obtained on PET data. On MRI scans, primary tumor size, diffusion and perfusion parameters were assessed using pre-contrast and high-resolution post-contrast images. Ratios between metabolic/metabolo-volumetric parameters and ADC were calculated. Comparisons between groups were performed by Student's t test. Survival analysis was performed by univariate Cox proportional hazard regression analysis. Overall survival curves were obtained by the Kaplan-Meier method and compared with the log-rank test. Survivors were censored at the time of the last clinical control. p < 0.05 was considered statistically significant RESULTS: During follow-up (mean 31.4 ± 21 months), there were 15 deaths. Univariate analysis shows that SULpeak and SULpeak/ADCmean were significant predictors of overall survival (OS). At multivariate analysis, only SULpeak remained a significant predictor of OS. Kaplan-Meier survival analyses showed that patients with higher SULpeak had poorer outcome compared to those with lower values (HR: 3.7, p = 0.007).

Conclusion: Pre-therapy SULpeak of the primary site was predictive of overall survival in patients with oropharyngeal or hypopharyngeal cancer treated with (chemo)radiotherapy.
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http://dx.doi.org/10.1007/s12149-021-01590-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7981313PMC
April 2021

First and second wave of SARS-CoV2 in Italian Cystic Fibrosis patients: Data from Italian Cystic Fibrosis Registry.

J Cyst Fibros 2021 Mar 26;20(2):372-373. Epub 2021 Jan 26.

National Center Rare Diseases, Undiagnosed Rare Diseases Interdepartmental Unit, Istituto Superiore di Sanità, Rome, Italy.

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http://dx.doi.org/10.1016/j.jcf.2021.01.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7835102PMC
March 2021

Gender Brain Structural Differences and Interoception.

Front Neurosci 2020 6;14:586860. Epub 2021 Jan 6.

IRCCS SDN, Naples, Italy.

Interoception, the ability to perceive inner body sensations, has been demonstrated to be different among genders, with a stronger female attention toward interoceptive information. No study correlated this capability with brain differences between males and females. This study aims to detect behavioral variances and structural neuroimaging interoception correlates in a sample of healthy volunteers matched for age. Seventy-three participants (37 females, mean age 43.5; 36 males, mean age 37.4) completed the Self-Awareness Questionnaire (SAQ) for interoceptive sensibility and underwent a structural MRI session. A test corrected for Bonferroni multiple comparisons was performed to compare brain morphological parameters (cortical thickness and parcel volume) in both groups. A multivariate analysis of variance was performed to assess the effect of gender on scores obtained on the SAQ. A moderation model through multiple linear regression analysis was performed between gray matter volumes or parcels, cortical thickness, and the interoception score. Group analysis showed significant differences in morphometric brain data between males and females, both for cortical and subcortical volumes, but not for cortical thickness analyses. MANOVA underlined a significant difference in SAQ scores between males and females with higher values for the second ones. Moreover, a significant correlation between the interoception scores and gray matter volumes of the two groups has been detected, with a sharp prevalence for the female gender in the left insula with F1, F2, and SAQ interoception scores ( = 0.41, < 0.001). Our results demonstrated that in the female group, a stronger predisposition was found toward interoceptive sensations, and that multiple brain areas were correlated with interoceptive measure. These data sustain a female advantage in the attention toward this process and support the idea that interoception in females is a process more shared across several regions that participate in creating the sense of self.
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http://dx.doi.org/10.3389/fnins.2020.586860DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7815642PMC
January 2021

Whole Body Low Dose Computed Tomography Using Third-Generation Dual-Source Multidetector With Spectral Shaping: Protocol Optimization and Literature Review.

Dose Response 2020 Oct-Dec;18(4):1559325820973131. Epub 2020 Dec 29.

IRCCS SDN, Naples, Italy.

For decades, the main imaging tool for multiple myeloma (MM) patient's management has been the conventional skeleton survey. In 2014 international myeloma working group defined the advantages of the whole-body low dose computed tomography (WBLDCT) as a gold standard, among imaging modalities, for bone disease assessment and subsequently implemented this technique in the MM diagnostic workflow. The aim of this study is to investigate, in a group of 30 patients with a new diagnosis of MM, the radiation dose (CT dose index, dose-length product, effective dose), the subjective image quality score and osseous/extra-osseous findings rate with a modified WBLDCT protocol. Spectral shaping and third-generation dual-source multidetector CT scanner was used for the assessment of osteolytic lesions due to MM, and the dose exposure was compared with the literature findings reported until 2020. Mean radiation dose parameters were reported as follows: CT dose index 0.3 ± 0.1 mGy, Dose-Length Product 52.0 ± 22.5 mGy*cm, effective dose 0.44 ± 0.19 mSv. Subjective image quality was good/excellent in all subjects. 11/30 patients showed osteolytic lesions, with a percentage of extra-osseous findings detected in 9/30 patients. Our data confirmed the advantages of WBLDCT in the diagnosis of patients with MM, reporting an effective dose for our protocol as the lowest among previous literature findings.
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http://dx.doi.org/10.1177/1559325820973131DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7783892PMC
December 2020

MuSA: a graphical user interface for multi-OMICs data integration in radiogenomic studies.

Sci Rep 2021 Jan 15;11(1):1550. Epub 2021 Jan 15.

IRCCS SDN, Via E. Gianturco, 113, 80143, Naples, Italy.

Analysis of large-scale omics data along with biomedical images has gaining a huge interest in predicting phenotypic conditions towards personalized medicine. Multiple layers of investigations such as genomics, transcriptomics and proteomics, have led to high dimensionality and heterogeneity of data. Multi-omics data integration can provide meaningful contribution to early diagnosis and an accurate estimate of prognosis and treatment in cancer. Some multi-layer data structures have been developed to integrate multi-omics biological information, but none of these has been developed and evaluated to include radiomic data. We proposed to use MultiAssayExperiment (MAE) as an integrated data structure to combine multi-omics data facilitating the exploration of heterogeneous data. We improved the usability of the MAE, developing a Multi-omics Statistical Approaches (MuSA) tool that uses a Shiny graphical user interface, able to simplify the management and the analysis of radiogenomic datasets. The capabilities of MuSA were shown using public breast cancer datasets from TCGA-TCIA databases. MuSA architecture is modular and can be divided in Pre-processing and Downstream analysis. The pre-processing section allows data filtering and normalization. The downstream analysis section contains modules for data science such as correlation, clustering (i.e., heatmap) and feature selection methods. The results are dynamically shown in MuSA. MuSA tool provides an easy-to-use way to create, manage and analyze radiogenomic data. The application is specifically designed to guide no-programmer researchers through different computational steps. Integration analysis is implemented in a modular structure, making MuSA an easily expansible open-source software.
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http://dx.doi.org/10.1038/s41598-021-81200-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7811020PMC
January 2021

Evaluation of a multiparametric MRI radiomic-based approach for stratification of equivocal PI-RADS 3 and upgraded PI-RADS 4 prostatic lesions.

Sci Rep 2021 Jan 12;11(1):643. Epub 2021 Jan 12.

IRCCS SDN, Naples, Italy.

Despite the key-role of the Prostate Imaging and Reporting and Data System (PI-RADS) in the diagnosis and characterization of prostate cancer (PCa), this system remains to be affected by several limitations, primarily associated with the interpretation of equivocal PI-RADS 3 lesions and with the debated role of Dynamic Contrast Enhanced-Magnetic Resonance Imaging (DCE-MRI), which is only used to upgrade peripheral PI-RADS category 3 lesions to PI-RADS category 4 if enhancement is focal. We aimed at investigating the usefulness of radiomics for detection of PCa lesions (Gleason Score ≥ 6) in PI-RADS 3 lesions and in peripheral PI-RADS 3 upgraded to PI-RADS 4 lesions (upPI-RADS 4). Multiparametric MRI (mpMRI) data of patients who underwent prostatic mpMRI between April 2013 and September 2018 were retrospectively evaluated. Biopsy results were used as gold standard. PI-RADS 3 and PI-RADS 4 lesions were re-scored according to the PI-RADS v2.1 before and after DCE-MRI evaluation. Radiomic features were extracted from T2-weighted MRI (T2), Apparent diffusion Coefficient (ADC) map and DCE-MRI subtracted images using PyRadiomics. Feature selection was performed using Wilcoxon-ranksum test and Minimum Redundancy Maximum Relevance (mRMR). Predictive models were constructed for PCa detection in PI-RADS 3 and upPI-RADS 4 lesions using at each step an imbalance-adjusted bootstrap resampling (IABR) on 1000 samples. 41 PI-RADS 3 and 32 upPI-RADS 4 lesions were analyzed. Among 293 radiomic features, the top selected features derived from T2 and ADC. For PI-RADS 3 stratification, second order model showed higher performances (Area Under the Receiver Operating Characteristic Curve-AUC- = 80%), while for upPI-RADS 4 stratification, first order model showed higher performances respect to superior order models (AUC = 89%). Our results support the significant role of T2 and ADC radiomic features for PCa detection in lesions scored as PI-RADS 3 and upPI-RADS 4. Radiomics models showed high diagnostic efficacy in classify PI-RADS 3 and upPI-RADS 4 lesions, outperforming PI-RADS v2.1 performance.
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http://dx.doi.org/10.1038/s41598-020-80749-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7804929PMC
January 2021

An Integrative Computational Approach Based on Expression Similarity Signatures to Identify Protein-Protein Interaction Networks in Female-Specific Cancers.

Front Genet 2020 3;11:612521. Epub 2020 Dec 3.

IRCCS SDN, Naples, Italy.

Breast, ovarian, and endometrial cancers have a major impact on mortality in women. These tumors share hormone-dependent mechanisms involved in female-specific cancers which support tumor growth in a different manner. Integrated computational approaches may allow us to better detect genomic similarities between these different female-specific cancers, helping us to deliver more sophisticated diagnosis and precise treatments. Recently, several initiatives of The Cancer Genome Atlas (TCGA) have encouraged integrated analyses of multiple cancers rather than individual tumors. These studies revealed common genetic alterations (driver genes) even in clinically distinct entities such as breast, ovarian, and endometrial cancers. In this study, we aimed to identify expression similarity signatures by extracting common genes among TCGA breast (BRCA), ovarian (OV), and uterine corpus endometrial carcinoma (UCEC) cohorts and infer co-regulatory protein-protein interaction networks that might have a relationship with the estrogen signaling pathway. Thus, we carried out an unsupervised principal component analysis (PCA)-based computational approach, using RNA sequencing data of 2,015 female cancer and 148 normal samples, in order to simultaneously capture the data heterogeneity of intertumors. Firstly, we identified tumor-associated genes from gene expression profiles. Secondly, we investigated the signaling pathways and co-regulatory protein-protein interaction networks underlying these three cancers by leveraging the Ingenuity Pathway Analysis software. In detail, we discovered 1,643 expression similarity signatures (638 downregulated and 1,005 upregulated genes, with respect to normal phenotype), denoted as tumor-associated genes. Through functional genomic analyses, we assessed that these genes were involved in the regulation of cell-cycle-dependent mechanisms, including metaphase kinetochore formation and estrogen-dependent S-phase entry. Furthermore, we generated putative co-regulatory protein-protein interaction networks, based on upstream regulators such as the ERBB2/HER2 gene. Moreover, we provided an bioinformatics workflow with a manageable list of intertumor expression similarity signatures for the three female-specific cancers. The expression similarity signatures identified in this study might uncover potential estrogen-dependent molecular mechanisms promoting carcinogenesis.
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http://dx.doi.org/10.3389/fgene.2020.612521DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7793872PMC
December 2020

From Uncommon Infection to Multi-Cranial Palsy: Malignant External Otitis Insights.

Dose Response 2020 Oct-Dec;18(4):1559325820963910. Epub 2020 Dec 17.

Department of Medical and Surgical Sciences and Advanced Technologies "GF Ingrassia," ENT Section, University of Catania, Catania, Italy.

Purpose: The progression of the otitic infectious process toward diseases of particular severity is often unpredictable, just as it is challenging to manage the patient over time, even after the apparent resolution of the disease. We aim to define a radiological reading key that allows us to correctly and promptly treat the disease, avoiding the possible severe complications.

Methods: We conducted a retrospective study of 13 cases of basal cranial osteomyelitis (SBO) due to malignant external otitis, by the ENT Department of the University of Catania. Through a standardized approach and following the latest guidelines, we have evaluated all patients performing a standardized and personalized radiological protocol according to the stage of the patient's pathology and modulating the treatment consequently.

Results: Clinical signs have been observed such as otorrhea (100%), otalgia in 13/13 patients (100%), granulations in external auditory canal (100%), preauricular cellulitis in 9/13 patients (69%) headache 6/13 cases (46%), dysphonia 4/13 cases (31%). HRCT of the temporal bone proved useful in identifying even minimal bone lesions in 13/13 (100%) while improving MRI in vascular and nervous involvement, although in 1/13 patient with nerve palsy clinical symptomatology preceded radiological evidence. The 99mTc 3-phase planar bone scintigraphy was positive for SBO in 9/13 cases (69%) during the initial phase and, in 100% of the cases in images delayed to 2-3 hours. Subsequent checks up to 1 year, using the Ga 67 scintigraphy, excluded the presence of recurrences in 100% of patients.

Conclusion: The osteomyelitis of the base of the skull is a severe complication of malignant external otitis, often not always easily diagnosed. Recurrence can occur up to 1 year after stopping therapy. Imaging techniques such as Tc and MRI are relevant for the initial diagnostic approach and the staging of the pathology and its complications. Nuclear medicine imaging plays a fundamental role in the evaluation of related osteoblastic activity, especially in the remission phase of the disease.
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http://dx.doi.org/10.1177/1559325820963910DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7750775PMC
December 2020

Role of Low-Molecular-Weight Heparin in Hospitalized Patients With Severe Acute Respiratory Syndrome Coronavirus 2 Pneumonia: A Prospective Observational Study.

Open Forum Infect Dis 2020 Dec 19;7(12):ofaa563. Epub 2020 Nov 19.

Infectious Disease Unit, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.

Background: This study was conducted to evaluate the impact of low-molecular-weight heparin (LMWH) on the outcome of patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia.

Methods: This is a prospective observational study including consecutive patients with laboratory-confirmed SARS-CoV-2 pneumonia admitted to the University Hospital of Pisa (March 4-April 30, 2020). Demographic, clinical, and outcome data were collected. The primary endpoint was 30-day mortality. The secondary endpoint was a composite of death or severe acute respiratory distress syndrome (ARDS). Low-molecular-weight heparin, hydroxychloroquine, doxycycline, macrolides, antiretrovirals, remdesivir, baricitinib, tocilizumab, and steroids were evaluated as treatment exposures of interest. First, a Cox regression analysis, in which treatments were introduced as time-dependent variables, was performed to evaluate the association of exposures and outcomes. Then, a time-dependent propensity score (PS) was calculated and a PS matching was performed for each treatment variable.

Results: Among 315 patients with SARS-CoV-2 pneumonia, 70 (22.2%) died during hospital stay. The composite endpoint was achieved by 114 (36.2%) patients. Overall, 244 (77.5%) patients received LMWH, 238 (75.5%) received hydroxychloroquine, 201 (63.8%) received proteases inhibitors, 150 (47.6%) received doxycycline, 141 (44.8%) received steroids, 42 (13.3%) received macrolides, 40 (12.7%) received baricitinib, 13 (4.1%) received tocilizumab, and 13 (4.1%) received remdesivir. At multivariate analysis, LMWH was associated with a reduced risk of 30-day mortality (hazard ratio [HR], 0.36; 95% confidence interval [CI], 0.21-0.6;  < .001) and composite endpoint (HR, 0.61; 95% CI, 0.39-0.95;  = .029). The PS-matched cohort of 55 couples confirmed the same results for both primary and secondary endpoint.

Conclusions: This study suggests that LMWH might reduce the risk of in-hospital mortality and severe ARDS in coronavirus disease 2019. Randomized controlled trials are warranted to confirm these preliminary findings.
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http://dx.doi.org/10.1093/ofid/ofaa563DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7717381PMC
December 2020

Clinical characteristics of SARS-CoV-2 infection in children with cystic fibrosis: An international observational study.

J Cyst Fibros 2021 01 3;20(1):25-30. Epub 2020 Dec 3.

Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, United Kingdom; Paediatric Respiratory Medicine, Great North Children's Hospital, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, United Kingdom. Electronic address:

Background: The presence of co-morbidities, including underlying respiratory problems, has been identified as a risk factor for severe COVID-19 disease. Information on the clinical course of SARS-CoV-2 infection in children with cystic fibrosis (CF) is limited, yet vital to provide accurate advice for children with CF, their families, caregivers and clinical teams.

Methods: Cases of SARS-CoV-2 infection in children with CF aged less than 18 years were collated by the CF Registry Global Harmonization Group across 13 countries between 1 February and 7 August 2020.

Results: Data on 105 children were collated and analysed. Median age of cases was ten years (interquartile range 6-15), 54% were male and median percentage predicted forced expiratory volume in one second was 94% (interquartile range 79-104). The majority (71%) of children were managed in the community during their COVID-19 illness. Out of 24 children admitted to hospital, six required supplementary oxygen and two non-invasive ventilation. Around half were prescribed antibiotics, five children received antiviral treatments, four azithromycin and one additional corticosteroids. Children that were hospitalised had lower lung function and reduced body mass index Z-scores. One child died six weeks after testing positive for SARS-CoV-2 following a deterioration that was not attributed to COVID-19 disease.

Conclusions: SARS-CoV-2 infection in children with CF is usually associated with a mild illness in those who do not have pre-existing severe lung disease.
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http://dx.doi.org/10.1016/j.jcf.2020.11.021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7713571PMC
January 2021

Accuracy and reproducibility of automated white matter hyperintensities segmentation with lesion segmentation tool: A European multi-site 3T study.

Magn Reson Imaging 2021 02 19;76:108-115. Epub 2020 Nov 19.

Laboratory of Alzheimer's Neuroimaging and Alzheimer's Epidemiology, IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy.

Brain vascular damage accumulate in aging and often manifest as white matter hyperintensities (WMHs) on MRI. Despite increased interest in automated methods to segment WMHs, a gold standard has not been achieved and their longitudinal reproducibility has been poorly investigated. The aim of present work is to evaluate accuracy and reproducibility of two freely available segmentation algorithms. A harmonized MRI protocol was implemented in 3T-scanners across 13 European sites, each scanning five volunteers twice (test-retest) using 2D-FLAIR. Automated segmentation was performed using Lesion segmentation tool algorithms (LST): the Lesion growth algorithm (LGA) in SPM8 and 12 and the Lesion prediction algorithm (LPA). To assess reproducibility, we applied the LST longitudinal pipeline to the LGA and LPA outputs for both the test and retest scans. We evaluated volumetric and spatial accuracy comparing LGA and LPA with manual tracing, and for reproducibility the test versus retest. Median volume difference between automated WMH and manual segmentations (mL) was -0.22[IQR = 0.50] for LGA-SPM8, -0.12[0.57] for LGA-SPM12, -0.09[0.53] for LPA, while the spatial accuracy (Dice Coefficient) was 0.29[0.31], 0.33[0.26] and 0.41[0.23], respectively. The reproducibility analysis showed a median reproducibility error of 20%[IQR = 41] for LGA-SPM8, 14% [31] for LGA-SPM12 and 10% [27] with the LPA cross-sectional pipeline. Applying the LST longitudinal pipeline, the reproducibility errors were considerably reduced (LGA: 0%[IQR = 0], p < 0.001; LPA: 0% [3], p < 0.001) compared to those derived using the cross-sectional algorithms. The DC using the longitudinal pipeline was excellent (median = 1) for LGA [IQR = 0] and LPA [0.02]. LST algorithms showed moderate accuracy and good reproducibility. Therefore, it can be used as a reliable cross-sectional and longitudinal tool in multi-site studies.
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http://dx.doi.org/10.1016/j.mri.2020.11.008DOI Listing
February 2021

Cystic fibrosis with non-G551D gating mutations in Italy: Epidemiology and clinical characteristics.

Pediatr Pulmonol 2021 Feb 27;56(2):442-449. Epub 2020 Nov 27.

Italian Cystic Fibrosis Registry, Rome, Italy.

Background: Cystic fibrosis transmembrane conductance regulator (CFTR) gating mutations (GMs) result in CFTR that is present at the cell surface but nonfunctional. Patients with the G551D mutation, the most prevalent worldwide, have been well studied. Italian GM patients have mainly non-G551D mutations. We studied their epidemiology and clinical characteristics in the period spanning the pre/post ivacaftor introduction to the Italian market.

Methods: Data from the Italian CF Registry were used to describe patients with GMs and compare them with F508del homozygous (F/F) patients.

Results: In total, 186 patients with GMs (median [range] age, 21.96 [0.13-63.38] years) were identified among the 5552 patients included in the study (3.3%). They had lower sweat chloride values at diagnosis than the F/F and a lower ratio of males. In the GM group, examining the data of the years 2012 and 2017 and comparing with F/F, lung infection by Staphylococcus aureus and diabetes became less prevalent, and better FEV and nutritional status were observed in 2017. The cross-sectional evaluation year-by-year from 2012 to 2017 of the GM group showed improving trends in lung function and body mass index, and the decreasing prevalence of diabetes compared with F/F. Longitudinal evaluation of GM patients showed improvement in percent predicted (pp)FEV and nutrition in the 2012-2017 period. These variations correspond to the introduction of treatment with the CFTR potentiator ivacaftor (2014/2015).

Conclusions: Italian patients with GMs are few and are characterized by milder phenotypes than F/F patients. Improved outcomes are likely influenced by treatment with ivacaftor.
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http://dx.doi.org/10.1002/ppul.25179DOI Listing
February 2021

DNA methylation profiling of CD04/CD08 T cells reveals pathogenic mechanisms in increasing hyperglycemia: PIRAMIDE pilot study.

Ann Med Surg (Lond) 2020 Dec 20;60:218-226. Epub 2020 Oct 20.

Department of Advanced Medical and Surgical Sciences (DAMSS), University of Campania "Luigi Vanvitelli", 80138, Naples, Italy.

Background: DNA methylation can play a pathogenic role in the early stages of hyperglycemia linking homeostasis imbalance and vascular damage.

Material And Methods: We investigated DNA methylome by RRBS in CD04 and CD08 T cells from healthy subjects (HS) to pre-diabetics (Pre-Diab) and type 2 diabetic (T2D) patients to identify early biomarkers of glucose impairment and vascular damage. Our cross-sectional study enrolled 14 individuals from HS state to increasing hyperglycemia (pilot study, PIRAMIDE trial, NCT03792607).

Results: Globally, differentially methylated regions (DMRs) were mostly annotated to promoter regions. Hypermethylated DMRs were greater than hypomethylated in CD04 T cells whereas CD08 T showed an opposite trend. Moreover, DMRs overlapping between Pre-Diab and T2D patients were mostly hypermethylated in both T cells. Interestingly, was the most hypomethylated gene in Pre-Diab and its methylation level gradually decreased in T2D patients. Besides, showed a significant positive correlation with DBP (+0.76), HDL (+0.54), Creatinine (+0.83), LVDd (+0.98), LVSD (+0.98), LAD (+0.98), LVPWd (+0.84), AODd (+0.81), HR (+0.72), Triglycerides (+0.83), LAD (+0.69) and AODd (+0.52) whereas a negative correlation with Cholesterol (-0.52) and LDL (-0.71) in T2D.

Conclusion: hypomethylation in CD08 T cells may be a useful biomarker of vascular complications in Pre-Diab with a possible role for primary prevention warranting further multicenter clinical trials to validate our findings.
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http://dx.doi.org/10.1016/j.amsu.2020.10.016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7645316PMC
December 2020

JAK inhibition reduces SARS-CoV-2 liver infectivity and modulates inflammatory responses to reduce morbidity and mortality.

Sci Adv 2021 01 1;7(1). Epub 2021 Jan 1.

Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.

Using AI, we identified baricitinib as having antiviral and anticytokine efficacy. We now show a 71% (95% CI 0.15 to 0.58) mortality benefit in 83 patients with moderate-severe SARS-CoV-2 pneumonia with few drug-induced adverse events, including a large elderly cohort (median age, 81 years). An additional 48 cases with mild-moderate pneumonia recovered uneventfully. Using organotypic 3D cultures of primary human liver cells, we demonstrate that interferon-α2 increases ACE2 expression and SARS-CoV-2 infectivity in parenchymal cells by greater than fivefold. RNA-seq reveals gene response signatures associated with platelet activation, fully inhibited by baricitinib. Using viral load quantifications and superresolution microscopy, we found that baricitinib exerts activity rapidly through the inhibition of host proteins (numb-associated kinases), uniquely among antivirals. This reveals mechanistic actions of a Janus kinase-1/2 inhibitor targeting viral entry, replication, and the cytokine storm and is associated with beneficial outcomes including in severely ill elderly patients, data that incentivize further randomized controlled trials.
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http://dx.doi.org/10.1126/sciadv.abe4724DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7775747PMC
January 2021

The global impact of SARS-CoV-2 in 181 people with cystic fibrosis.

J Cyst Fibros 2020 11 4;19(6):868-871. Epub 2020 Nov 4.

Royal Brompton Hospital and Imperial College London, UK.

With the growing SARS-CoV-2 pandemic, we need to better understand its impact in specific patient groups like those with Cystic Fibrosis (CF). We report on 181 people with CF (32 post-transplant) from 19 countries diagnosed with SARS-CoV-2 prior to 13 June 2020. Infection with SARS-CoV-2 appears to exhibit a similar spectrum of outcomes to that seen in the general population, with 11 people admitted to intensive care (7 post-transplant), and 7 deaths (3 post-transplant). A more severe clinical course may be associated with older age, CF-related diabetes, lower lung function in the year prior to infection, and having received an organ transplant. Whilst outcomes in this large cohort are better than initially feared overall, possibly due to a protective effect of the relatively younger age of the CF population compared to other chronic conditions, SARS-CoV-2 is not a benign disease for all people in this patient group.
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http://dx.doi.org/10.1016/j.jcf.2020.10.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7641525PMC
November 2020

Migraine and Sport in a Physically Active Population of Students: Results of a Cross-Sectional Study.

Headache 2020 Nov 7;60(10):2330-2339. Epub 2020 Nov 7.

Department of Biomedicine, Neuroscience and Advanced Diagnostic (BIND), University of Palermo, Palermo, Italy.

Objective: In this study, we explored the relationship between migraine and sport in a physically active population of students, analyzing the risk of migraine among sporty students.

Background: The relationship between sport and migraine is controversial; moreover, several studies report on sport as a migraine trigger, but there is evidence that physical activity could have a relevant role in migraine prevention.

Methods: A cross-sectional survey was conducted using the validated ID-migraine questionnaire including specific demo-anthropometric (gender, age, weight, height) and sports variables on a potentially active student population of the University of Palermo. Evaluation in putative migraine subjects of clinical features and disability was explored through the administration of the Italian version of the Migraine Disability Assessment Scale. Statistical analyses were performed using univariate and logistic regression analyses.

Results: Three hundred and ninety-three out of 520 students (210 F, mean age: 23.5 ± 0.7 years; 183 M; mean age: 20.5 ± 0.7 years) participated in this study. Migraine screened positive in 102 subjects (26.0%) and its prevalence was significantly higher among females (P < .001). An increased risk of migraine was found in females, and a protective effect of sport on the risk of migraine among females, but not among males.

Conclusions: The role of exercise in migraine is still unclear. This study supports a protective role of sport in migraine reporting a protective effect in females. Further studies are needed to deepen the association between sport and migraine.
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http://dx.doi.org/10.1111/head.14015DOI Listing
November 2020

Short-Chain Fatty Acids and Lipopolysaccharide as Mediators Between Gut Dysbiosis and Amyloid Pathology in Alzheimer's Disease.

J Alzheimers Dis 2020 ;78(2):683-697

Memory Clinic and LANVIE - Laboratory of Neuroimaging of Aging, University Hospitals and University of Geneva, Geneva, Switzerland.

Background: Metagenomic data support an association between certain bacterial strains and Alzheimer's disease (AD), but their functional dynamics remain elusive.

Objective: To investigate the association between amyloid pathology, bacterial products such as lipopolysaccharide (LPS) and short chain fatty acids (SCFAs: acetate, valerate, butyrate), inflammatory mediators, and markers of endothelial dysfunction in AD.

Methods: Eighty-nine older persons with cognitive performance from normal to dementia underwent florbetapir amyloid PET and blood collection. Brain amyloidosis was measured with standardized uptake value ratio versus cerebellum. Blood levels of LPS were measured by ELISA, SCFAs by mass spectrometry, cytokines by using real-time PCR, and biomarkers of endothelial dysfunction by flow cytometry. We investigated the association between the variables listed above with Spearman's rank test.

Results: Amyloid SUVR uptake was positively associated with blood LPS (rho≥0.32, p≤0.006), acetate and valerate (rho≥0.45, p < 0.001), pro-inflammatory cytokines (rho≥0.25, p≤0.012), and biomarkers of endothelial dysfunction (rho≥0.25, p≤0.042). In contrast, it was negatively correlated with butyrate (rho≤-0.42, p≤0.020) and the anti-inflammatory cytokine IL10 (rho≤-0.26, p≤0.009). Endothelial dysfunction was positively associated with pro-inflammatory cytokines, acetate and valerate (rho≥0.25, p≤0.045) and negatively with butyrate and IL10 levels (rho≤-0.25, p≤0.038).

Conclusion: We report a novel association between gut microbiota-related products and systemic inflammation with brain amyloidosis via endothelial dysfunction, suggesting that SCFAs and LPS represent candidate pathophysiologic links between the gut microbiota and AD pathology.
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http://dx.doi.org/10.3233/JAD-200306DOI Listing
January 2020

The Covid-19, Epidemiology, Clinic and Prevention.

Curr Genomics 2020 Apr;21(3):157

1Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy; 2Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy; 3U.O. 5 Medicine, AOUP, Pisa, Italy.

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http://dx.doi.org/10.2174/1389202921999200427133052DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7521034PMC
April 2020

Improving staging of rectal cancer in the pelvis: the role of PET/MRI.

Eur J Nucl Med Mol Imaging 2021 Apr 9;48(4):1235-1245. Epub 2020 Oct 9.

Department of Radiology, Massachusetts General Hospital, Harvard Medical School, White Building Rm 250, 55 Fruit St, Boston, MA, 02114, USA.

Purpose: The role of positron emission tomography/magnetic resonance (PET/MR) in evaluating the local extent of rectal cancer remains uncertain. This study aimed to investigate the possible role of PET/MR versus magnetic resonance (MR) in clinically staging rectal cancer.

Methods: This retrospective two-center cohort study of 62 patients with untreated rectal cancer investigated the possible role of baseline staging PET/MR versus stand-alone MR in determination of clinical stage. Two readers reviewed T and N stage, mesorectal fascia involvement, tumor length, distance from the anal verge, sphincter involvement, and extramural vascular invasion (EMVI). Sigmoidoscopy, digital rectal examination, and follow-up imaging, along with surgery when available, served as the reference standard.

Results: PET/MR outperformed MR in evaluating tumor size (42.5 ± 21.03 mm per the reference standard, 54 ± 20.45 mm by stand-alone MR, and 44 ± 20 mm by PET/MR, P = 0.004), and in identifying N status (correct by MR in 36/62 patients [58%] and by PET/MR in 49/62 cases [79%]; P = 0.02) and external sphincter infiltration (correct by MR in 6/10 and by PET/MR in 9/10; P = 0.003). No statistically significant differences were observed in relation to any other features.

Conclusion: PET/MR provides a more precise assessment of the local extent of rectal cancers in evaluating cancer length, N status, and external sphincter involvement. PET/MR offers the opportunity to improve clinical decision-making, especially when evaluating low rectal tumors with possible external sphincter involvement.
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http://dx.doi.org/10.1007/s00259-020-05036-xDOI Listing
April 2021

Predicting Survival in Glioblastoma Patients Using Diffusion MR Imaging Metrics-A Systematic Review.

Cancers (Basel) 2020 Oct 4;12(10). Epub 2020 Oct 4.

IRCCS SDN (Istituto di Ricovero e Cura a Carattere Scientifico, SYNLAB istituto di Diagnostica Nucleare), 80131 Naples, Italy.

Despite advances in surgical and medical treatment of glioblastoma (GBM), the medium survival is about 15 months and varies significantly, with occasional longer survivors and individuals whose tumours show a significant response to therapy with respect to others. Diffusion MRI can provide a quantitative assessment of the intratumoral heterogeneity of GBM infiltration, which is of clinical significance for targeted surgery and therapy, and aimed at improving GBM patient survival. So, the aim of this systematic review is to assess the role of diffusion MRI metrics in predicting survival of patients with GBM. According to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement, a systematic literature search was performed to identify original articles since 2010 that evaluated the association of diffusion MRI metrics with overall survival (OS) and progression-free survival (PFS). The quality of the included studies was evaluated using the QUIPS tool. A total of 52 articles were selected. The most examined metrics were associated with the standard Diffusion Weighted Imaging (DWI) (34 studies) and Diffusion Tensor Imaging (DTI) models (17 studies). Our findings showed that quantitative diffusion MRI metrics provide useful information for predicting survival outcomes in GBM patients, mainly in combination with other clinical and multimodality imaging parameters.
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http://dx.doi.org/10.3390/cancers12102858DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7600641PMC
October 2020

Novel TONSL variants cause SPONASTRIME dysplasia and associate with spontaneous chromosome breaks, defective cell proliferation and apoptosis.

Hum Mol Genet 2020 Nov;29(18):3122-3131

Division of Medical Genetics, Fondazione IRCCS, Casa Sollievo della Sofferenza, 71013 San Giovanni Rotondo, Italy.

SPONASTRIME dysplasia is an ultrarare spondyloepimetaphyseal dysplasia featuring short stature and short limbs, platyspondyly, depressed nasal bridge with midface hypoplasia and striated metaphyses. In 2019, an autosomal recessive inheritance was demonstrated by the identification of bi-allelic hypomorphic alleles in TONSL. The encoded protein has a critical role in maintaining genome integrity by promoting the homologous recombination required for repairing spontaneous replication-associated DNA lesions at collapsed replication forks. We report a 9-year-old girl with typical SPONASTRIME dysplasia and resulted in carrier of the novel missense p.(Gln430Arg) and p.(Leu1090Arg) variants in TONSL at whole-exome sequencing. In silico analysis predicted that these variants induced thermodynamic changes with a pathogenic impact on protein function. To support the pathogenicity of the identified variants, cytogenetic analysis and microscopy assays showed that patient-derived fibroblasts exhibited spontaneous chromosomal breaks and flow cytometry demonstrated defects in cell proliferation and enhanced apoptosis. These findings contribute to our understanding of the molecular pathogenesis of SPONASTRIME dysplasia and might open the way to novel therapeutic approaches.
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http://dx.doi.org/10.1093/hmg/ddaa195DOI Listing
November 2020