Incidental extravascular findings in computed tomographic angiography for planning or monitoring endovascular aortic aneurysm repair: Smoker patients, increased lung cancer prevalence?

AIMTo validate the feasibility of high resolution computed tomography (HRCT) of the lung prior to computed tomography angiography (CTA) in assessing incidental thoracic findings during endovascular aortic aneurysm repair (EVAR) planning or follow-up.METHODSWe conducted a retrospective study among 181 patients (143 men, mean age 71 years, range 50-94) referred to our centre for CTA EVAR planning or follow-up. HRCT and CTA were performed before or after 1 or 12 mo respectively to EVAR in all patients. All HRCT examinations were reviewed by two radiologists with 15 and 8 years' experience in thoracic imaging. The results were compared with histology, bronchoscopy or follow-up HRCT in 12, 8 and 82 nodules respectively.RESULTSThere were a total of 102 suspected nodules in 92 HRCT examinations, with a mean of 1.79 nodules per patient and an average diameter of 9.2 mm (range 4-56 mm). Eighty-nine out of 181 HRCTs resulted negative for the presence of suspected nodules with a mean smoking history of 10 pack-years (p-y, range 5-18 p-y). Eighty-two out of 102 (76.4%) of the nodules met criteria for computed tomography follow-up, to exclude the malignant evolution. Of the remaining 20 nodules, 10 out of 20 (50%) nodules, suspected for malignancy, underwent biopsy and then surgical intervention that confirmed the neoplastic nature: 4 (20%) adenocarcinomas, 4 (20%) squamous cell carcinomas, 1 (5%) small cell lung cancer and 1 (5%) breast cancer metastasis); 8 out of 20 (40%) underwent bronchoscopy (8 pneumonia) and 2 out of 20 (10%) underwent biopsy with the diagnosis of sarcoidosis.CONCLUSIONHRCT in EVAR planning and follow-up allows to correctly identify patients requiring additional treatments, especially in case of lung cancer

Magnetic resonance lymphangiography: with or without contrast?

Lymphedema is an important medical issue around the world, caused by an anomalous collection of fluid in soft tissue due to congenital malformations or stenosis or obstruction of lymphatic vessels. Magnetic resonance lymphangiography (MRL) is an emerging technique focused on noninvasive or minimally invasive imaging of lymphatics with the goal to diagnose and treat lymphedema. This review will briefly discuss lymphatic imaging starting with lymphography and radionuclide lymphoscintigraphy up to the newest methods, focusing on MRL, a rising technique, and highlighting the technical aspects fundamental for achieving high-resolution MRL

Myelodysplastic syndromes: advantages of a combined cytogenetic and molecular diagnostic workup

In this study we present a new diagnostic workup for the myelodysplastic syndromes (MDS) including FISH, aCGH, and somatic mutation assays in addition to the conventional cytogenetics (CC). We analyzed 61 patients by CC, FISH for chromosome 5, 7, 8 and PDGFR rearrangements, aCGH, and PCR for ASXL1, EZH2, TP53, TET2, RUNX1, DNMT3A, SF3B1 somatic mutations. Moreover, we quantified WT1 and RPS14 gene expression levels, in order to find their possible adjunctive value and their possible clinical impact. CC analysis showed 32% of patients with at least one aberration. FISH analysis detected chromosomal aberrations in 24% of patients and recovered 5 cases (13.5%) at normal karyotype (two 5q- syndromes, one del(7) case, two cases with PDGFR rearrangement). The aGCH detected 10 "new" unbalanced cases in respect of the CC, including one with alteration of the ETV6 gene. After mutational analysis, 33 patients (54%) presented at least one mutation and represented the only marker of clonality in 36% of all patients. The statistical analysis confirmed the prognostic role of CC either on overall or on progression-free-survival. In addition, deletions detected by aCGH and WT1 over-expression negatively conditioned survival. In conclusion, our work showed that 1) the addition of FISH (at least for chr. 5 and 7) can improve the definition of the risk score; 2) mutational analysis, especially for the TP53 and SF3B1, could better define the type of MDS and represent a "clinical warning"; 3) the aCGH use could be probably applied to selected cases (with suboptimal response or failure)

Magnetic resonance imaging: Is there a role in clinical management for acute ischemic colitis?

AIM: To validate the utility of magnetic resonance imaging (MRI) for the clinical management of acute ischemic colitis (IC). METHODS: This is a magnetic resonance (MR) prospective evaluation of 7 patients who were proved to have acute IC on the basis of clinical, endoscopic and computed tomography (CT) findings and who were imaged in our institution between February 2011 and July 2012. The mean age of the patients was 72.28 years. Abdominal CTs were obtained using a 64-detector row configuration for all patients with un-enhanced and contrast-enhanced scans, in the late arterial phase (start delay 45-50 s) and in the portal venous phase (start delay 70-80 s). The MR examinations were performed using a 1.5T superconducting magnet, using Fast Imaging Employing Steady State Acquisition and T2-weighted fast-recovery fast-spin echo sequences in axial and coronal plane. CT and MRI examinations were analysed for the presence of colonic abnormalities and associated findings. RESULTS: Segmental involvement was seen in 6 patients (85.71%), with a mean length of involvement of 412 mm (range 145.5-1000 mm). Wall thickness varied between 6 mm and 17.5 mm (mean 10.52 mm) upon CT examinations and from 5 to 15 mm (mean 8.8 mm) upon MR examinations. The MRI appearance of the colonic wall varied over the time: Type I appearance with a 3 layer sandwich sign was seen in 5 out of 12 examinations (41.66%), patients underwent MR within a mean of 36 h (ranging from 1 to 54 h) after the CT examination. Type II and III appearance with a 2 layer sign, was seen in 4 examinations (33.33%), patients underwent MR within a mean of 420.5 h (ranging from 121 to 720 h) after the CT examination. In the remaining three MRI examinations, performed within a mean of 410 h (ranging from 99.5 to 720 h) the colonic wall appeared normal. CONCLUSION: MRI, only using precontrast images, may be used as a substitute for invasive procedures in diagnosis and follow-up of acute IC

Widespread genomic influences on phenotype in Dravet syndrome, a 'monogenic' condition

Dravet syndrome is an archetypal rare severe epilepsy, considered "monogenic", typically caused by loss-of-function SCN1A variants. Despite a recognisable core phenotype, its marked phenotypic heterogeneity is incompletely explained by differences in the causal SCN1A variant or clinical factors. In 34 adults with SCN1A-related Dravet syndrome, we show additional genomic variation beyond SCN1A contributes to phenotype and its diversity, with an excess of rare variants in epilepsy-related genes as a set and examples of blended phenotypes, including one individual with an ultra-rare DEPDC5 variant and focal cortical dysplasia. Polygenic risk scores for intelligence are lower, and for longevity, higher, in Dravet syndrome than in epilepsy controls. The causal, major-effect, SCN1A variant may need to act against a broadly compromised genomic background to generate the full Dravet syndrome phenotype, whilst genomic resilience may help to ameliorate the risk of premature mortality in adult Dravet syndrome survivors

Incidental and Underreported Pleural Plaques at Chest CT: Do Not Miss Them - Asbestos Exposure Still Exists

Pleural plaques (PPs) may be a risk factor for mortality from lung cancer in asbestos-exposed workers and are considered to be a marker of exposure. Diagnosing PPs is also important because asbestos-exposed patients should be offered a health surveillance that is mandatory in many countries. On the other hand PPs are useful for compensation purposes. In this study we aimed to evaluate the prevalence, as incidental findings, and the underreporting rate of PPs in chest CT scans (CTs) performed in a cohort of patients (1512) who underwent chest CT with a slice thickness no more than 1.25 mm. PPs were found in 76 out of 1482 patients (5.1%); in 13 out of 76 (17,1%) CTs were performed because of clinical suspicion of asbestos exposure and 5 of them (38%) were underreported by radiologist. In the remaining 63 cases (82.9%) there was no clinical suspicion of asbestos exposure at the time of CTs (incidental findings) and in 38 of these 63 patients (60.3%) PPs were underreported. Reaching a correct diagnosis of PPs requires a good knowledge of normal locoregional anatomy and rigorous technical approach in chest CT execution. However the job history of the patient should always be kept in mind

CT Perfusion in the Characterisation of Renal Lesions: An Added Value to Multiphasic CT

Objective. To prospectively evaluate if computed tomography perfusion (CTp) could be a useful tool in addition to multiphasic CT in renal lesion characterisation. Materials and Methods. Fifty-eight patients that were scheduled for surgical resection of a renal mass with a suspicion of renal cell carcinoma (RCC) were enrolled. Forty-one out of 58 patients underwent total or partial nephrectomy after CTp examination, and a pathological analysis was obtained for a total of 49 renal lesions. Perfusion parameters and attenuation values at multiphasic CT for both lesion and normal cortex were analysed. All the results were compared with the histological data obtained following surgery. Results. PS and MTT values were significantly lower in malignant lesions than in the normal cortex (P < 0.001 and P = 0.011, resp.); PS, MTT, and BF values were also statistically different between oncocytomas and malignant lesions. According to ROC analysis, the accuracy, sensitivity, and specificity to predict RCC were 95.92%, 100%, and 66.7%, respectively, for CTp whereas they were 89.80%, 93.35%, and 50%, respectively, for multiphasic CT. Conclusion. A significant difference between renal cortex and tumour CTp parameter values may suggest a malignant renal lesion. CTp could represent an added value to multiphasic CT in differentiating renal cells carcinoma from oncocytoma

A combined Raman-fluorescence spectroscopic probe for tissue diagnostics applications

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The Polycomb BMI1 Protein Is Co-expressed With CD26+ in Leukemic Stem Cells of Chronic Myeloid Leukemia

The Polycomb gene BMI1 expression exerts a negative predictive impact on several hematological malignancies, such as acute and chronic myeloid leukemia (CML), myelofibrosis, and follicular lymphoma. As already demonstrated in CML, BMI1 is responsible for the resistance to the tyrosine kinase inhibitors (TKIs) in a BCR-ABL1-independent way. Even if, it is unknown where BMI1 in CML is expressed (in progenitors or more mature cells). We decided, therefore, to evaluate if and where the BMI1 protein is located, focusing mainly on the CD34+/CD38-/CD26+ CML progenitors. To begin we measured, by flow cytometry, the proportion of CD34+/CD26+ cells in 31 bone marrow samples from 20 CML patients, at diagnosis and during treatment with imatinib. After that the bone marrow blood smears were stained with antibodies anti-CD26, BCR-ABL1, and BMI1. These smears were observed by a confocal laser microscope and a 3D reconstruction was then performed. At diagnosis, CD34+/CD26+ cells median value/μL was 0.48; this number increased from diagnosis to the third month of therapy and then reduced during treatment with imatinib. The number and behavior of the CD26+ progenitors were independent from the BCR-ABL1 expression, but they summed up what previously observed about the BMI1 expression modulation. In this work we demonstrate for the first time that in CML the BMI1 protein is co-expressed with BCR-ABL1 only in the cytoplasm of the CD26+ precursors; on the contrary, in other hematological malignancies where BMI1 is commonly expressed (follicular lymphoma, essential thrombocytemia, acute myeloid leukemia), it was not co-localized with CD26 or, obviously, with BCR-ABL1. Once translated into the clinical context, if BMI1 is a marker of stemness, our results would suggest the combination of the BMI1 inhibitors with TKIs as an interesting object of research, and, probably, as a promising way to overcome resistance in CML patients

An explainable model of host genetic interactions linked to COVID-19 severity

We employed a multifaceted computational strategy to identify the genetic factors contributing to increased risk of severe COVID-19 infection from a Whole Exome Sequencing (WES) dataset of a cohort of 2000 Italian patients. We coupled a stratified k-fold screening, to rank variants more associated with severity, with the training of multiple supervised classifiers, to predict severity based on screened features. Feature importance analysis from tree-based models allowed us to identify 16 variants with the highest support which, together with age and gender covariates, were found to be most predictive of COVID-19 severity. When tested on a follow-up cohort, our ensemble of models predicted severity with high accuracy (ACC = 81.88%; AUCROC = 96%; MCC = 61.55%). Our model recapitulated a vast literature of emerging molecular mechanisms and genetic factors linked to COVID-19 response and extends previous landmark Genome-Wide Association Studies (GWAS). It revealed a network of interplaying genetic signatures converging on established immune system and inflammatory processes linked to viral infection response. It also identified additional processes cross-talking with immune pathways, such as GPCR signaling, which might offer additional opportunities for therapeutic intervention and patient stratification. Publicly available PheWAS datasets revealed that several variants were significantly associated with phenotypic traits such as "Respiratory or thoracic disease", supporting their link with COVID-19 severity outcome.A multifaceted computational strategy identifies 16 genetic variants contributing to increased risk of severe COVID-19 infection from a Whole Exome Sequencing dataset of a cohort of Italian patients