Benign Enhancing Foramen Magnum Lesions.

Benign enhancing foramen magnum lesions have been previously described as T2-hyperintense small, enhancing lesions located posterior to the intradural vertebral artery. We present the first case with pathologic correlation. These lesions are fibrotic nodules adhering to the spinal accessory nerve. While they can enlarge with time on subsequent examinations, on the basis of the imaging characteristics and location, they do not necessitate surgical resection.

Erdheim-Chester Disease.

Erdheim-Chester disease is a rare non-Langerhans cell histiocytosis. The disease is widely variable in its severity, ranging from incidental findings in asymptomatic patients to a fatal multisystem illness. CNS involvement occurs in up to one-half of patients, most often leading to diabetes insipidus and cerebellar dysfunction. Imaging findings in neurologic Erdheim-Chester disease are often nonspecific, and the disease is commonly mistaken for close mimickers. Nevertheless, there are many imaging manifestations of Erdheim-Chester disease that are highly suggestive of the disease, which an astute radiologist could use to accurately indicate this diagnosis. This article discusses the imaging appearance, histologic features, clinical manifestations, and management of Erdheim-Chester disease.

Malignant Melanotic Nerve Sheath Tumor.

Malignant melanotic nerve sheath tumors are uncommon pigmented tumors of Schwann cell origin, most often found along the spinal nerves. Although well-described in the literature, the tumors are quite rare, making up <1% of nerve sheath tumors. Physicians are, therefore, often unfamiliar with both the appearance and the optimal treatment of such tumors. Morphologically, many imaging features overlap with schwannomas and neurofibromas. Nevertheless, the malignant melanotic nerve sheath tumors are crucial to identify. They can be extremely aggressive, and the management of these tumors is considerably different from their benign counterparts. In this radiology-pathology review, we will highlight the imaging appearance, histologic features, surgical resection, and subsequent therapeutic strategies in a patient with a lumbar malignant melanotic nerve sheath tumor.

Clinical impact and evolution of mitral regurgitation after TAVI using the new generation self-expandable valves.

BACKGROUND: Concomitant mitral regurgitation (MR) impaired prognosis in patients undergoing transcatheter aortic valve implantation (TAVI). It has been suggested that the use of first generation self-expandable valve in patients with significant MR is associated with worse outcome as compared with balloon expandable valve. However, the impact of newer generation transcatheter devices on MR has not been investigated so far. We aim to assess the prognostic impact of MR in patients undergoing TAVI with the first-generation vs. the latest generation of self-expandable valves. METHODS: We analyzed 2964 consecutive patients who underwent TAVI. Patients were classified into 4 groups according to the degree of baseline MR and the generation of self expandable valve implanted. RESULTS: Of 1234 patients with moderate or severe MR, 817 were treated with first generation and 417 patients with second generation valves. Whereas, of 1730 patients with no or mild MR, 1130 were treated with first generation and 600 patients with second generation valves. Although, concomitant moderate-severe MR was found to be an independent predictor of mortality after TAVI, the use of newer generation self expandable valves was associated with higher survival rate at 1 year irrespective of the degree of preprocedural MR. At multivariable analysis the use of newer generation valve was associated with MR improvement throughout 1 year follow-up. CONCLUSION: Baseline moderate-severe MR is associated with an increase in mortality after TAVI. However, the degree of preprocedural MR doesn't impact survival when a second generation self expandable valve is used.

Association of amyloid angiopathy with microbleeds in logopenic progressive aphasia: an imaging-pathology study.

BACKGROUND AND PURPOSE: Cerebral microbleeds (MB) and superficial siderosis (SS) are frequent neuroimaging findings in patients with logopenic progressive aphasia (LPA), often with frontal lobe predilection. Cerebral amyloid angiopathy (CAA) is hypothesized to be the major pathologic determinant of MB/SS in these patients; however, neuroimaging-pathologic data are limited. METHODS: All patients who had been prospectively recruited by the Neurodegenerative Research Group at the Mayo Clinic (Rochester, MN) between 2010 and 2015 and met the following inclusion criteria were included: (i) received an antemortem LPA diagnosis, (ii) had a gradient-recalled echo T2*-weighted magnetic resonance imaging (MRI) performed, (iii) died and completed a brain autopsy. Demographic, genetic, neuroimaging, and clinical and pathologic characteristics were compared between patients with/without MB/SS. Two-tailed Fisher exact and Wilcoxon rank sum tests were used for comparison of categorical and continuous variables, respectively. RESULTS: Thirteen patients met inclusion criteria, six (46%) had MB/SS on MRI. Moderate/severe CAA was associated with the presence of MB/SS (p = 0.029). As expected, MB/SS most frequently involved the frontal lobes, followed by the parietal lobes. No clear associations were found between regional MB/SS distribution and regional distribution of CAA or hypometabolism on [18 F]-fluorodeoxyglucose-positron emission tomography. There was some evidence for a regional association between MB/SS and uptake on Pittsburgh compound B, although not in all patients. No formal statistical analyses to assess topographic relationships were performed due to the small sample size. CONCLUSIONS: The presence of MB/SS is a strong indicator of underlying moderate/severe CAA in LPA, although the biological mechanisms underlying the topographic distribution of MB/SS remain unclear.

Optic Nerve Choristoma Mimicking a Neurenteric Cyst.

Optic nerve choristomas are rare entities in which a developmental focus of histologically normal tissue is abnormally located within or along a segment of the optic nerve. Although benign, choristomas may demonstrate slow growth, ultimately resulting in visual field deficits due to compression of the adjacent nerve in the few cases reported in the anterior fossa. Choristomas may have cystic components, though this has not been described in such lesions along the optic nerve. Here, a predominantly cystic optic nerve choristoma is described, with radiologic features mimicking those of an anterior cranial fossa neurenteric cyst. The case highlights the radiology-pathology correlates of choristomas and reviews the surgical approach and management of patients with such lesions.

Primary papillary epithelial tumour of the sella: expanding the spectrum of TTF-1-positive sellar lesions.

AIM: To describe four novel primary epithelial tumours of the sella with papillary architecture and Thyroid Transcription Factor 1 (TTF-1) expression. METHODS: Paraffin-embedded tissue from the four cases and recurrence of patient 1 was investigated with haematoxylin-eosin, special histochemical stains, immunohistochemistry with a broad panel of antibodies and next-generation sequencing. The ultrastructure of one tumour was studied in tissue retrieved from paraffin. RESULTS: The lesions occurred in three females aged 20, 26 and 42 years and a male aged 49 years. They presented with signs and symptoms secondary to pituitary stalk compression. Preoperative neuroimaging documented mixed solid and cystic, enhancing sellar masses with suprasellar extension. Histologically, the tumours showed thin papillae lined by a single layer of cytokeratin and TTF-1-positive cuboidal and cylindrical cells with mildly atypical nucleus. Next-generation sequencing performed in three cases did not identify any mutations. The main differential diagnosis included metastasis from lung or thyroid carcinoma, extraventricular choroid plexus papilloma and sellar ependymoma. CONCLUSION: We suggest the descriptive term of primary papillary epithelial tumour of the sella (PPETS) for this entity and propose that it could represent the intracranial equivalent of thyroid-like low-grade nasopharyngeal papillary adenocarcinoma. The cell of origin of PPETS remains undetermined although the intense and ubiquitous expression of TTF-1 may suggest a derivation from the infundibulum or ventricular recess. Our study expands the spectrum of sellar TTF-1-positive tumour and challenges the view that they all derive from pituicytes.

X-ray scanning microscopies of microcalcifications in abdominal aortic and popliteal artery aneurysms.

Abdominal aortic and popliteal artery aneurysms are vascular diseases which show massive degeneration, weakening of the vascular wall and loss of the vascular tissue functionality. They are driven by inflammatory, hemodynamical factors and biological alterations that may lead, in the case of an abdominal aortic aneurysm, to sudden and dangerous ruptures of the arteries. Here, human aortic and popliteal aneurysm tissues were obtained during surgical repair, and studied by synchrotron radiation X-ray scanning microdiffraction and small-angle scattering, to investigate the microcalcifications present in the tissues. Data collected during the experiments were transformed into quantitative microscopy images through the combination of statistical approaches and crystallographic methods. As a result of this multi-step analysis, microcalcifications, which are markers of the pathology, were classified in terms of chemical and structural content. This analysis helped to identify the presence of nanocrystalline hy-droxy-apatite and microcrystalline cholesterol, embedded in myofilament, and elastin-containing tissue with low collagen content in predominantly nanocrystalline areas. The generality of the approach allows it to be transferred to other types of tissue and other pathologies affected by microcalcifications, such as thyroid carcinoma, breast cancer, testicular microli-thia-sis or glioblastoma.

Validation of a clinicopathological score for the prediction of post-surgical evolution of pituitary adenoma: retrospective analysis on 566 patients from a tertiary care centre.

Objective and design A clinicopathological score has been proposed by Trouillas et al. to predict the evolution of pituitary adenomas. Aim of our study was to perform an independent external validation of this score and identify other potential predictor of post-surgical outcome. Methods The study sample included 566 patients with pituitary adenomas, specifically 253 FSH/LH-secreting, 147 GH-secreting, 85 PRL-secreting, 72 ACTH-secreting and 9 TSH-secreting tumours with at least 3-year post-surgical follow-up. Results In 437 cases, pituitary adenomas were non-invasive, with low (grade 1a: 378 cases) or high (grade 1b: 59 cases) proliferative activity. In 129 cases, tumours were invasive, with low (grade 2a: 87 cases) or high (grade 2b: 42 cases) proliferative activity. During the follow-up (mean: 5.8 years), 60 patients developed disease recurrence or progression, with a total of 130 patients with pituitary disease at last follow-up. Univariate analysis demonstrated a significantly higher risk of disease persistence and recurrence/progression in patients with PRL-, ACTH- and FSH/LH-secreting tumours as compared to those with somatotroph tumours, and in those with high proliferative activity (grade 1b and 2b) or >1 cm diameter. Multivariate analysis confirmed tumour type and grade to be independent predictors of disease-free-survival. Tumour invasion, Ki-67 and tumour type were the only independent prognostic factors of disease-free survival. Conclusions Our data confirmed the validity of Trouillas' score, being tumour type and grade independent predictors of disease evolution. Therefore, we recommend to always consider both features, together with tumour histological subtype, in the clinical setting to early identify patients at higher risk of recurrence.

Can a program of food and diabetes education improve the quality of the lives of diabetic patients with a previous myocardial infarction?

BACKGROUND AND OBJECTIVES: People with diabetes and cardiovascular complications need to be educated about the self-management of the disease at the time of diagnosis and during the follow-up to best benefit from what they learn. Education is most effective when offered to small groups of patients led by a professional team. The aim of the study is the evaluation of diabetes and food education aimed at improving the self-awareness of the disease, the management and the quality of the lives of diabetic patients with a previous myocardial infarction. METHODS AND RESULTS: The sample group consisted of 20 subjects suffering from diabetes mellitus type 2 with a previous myocardial infarction. First, subjects were administered a test to assess the degree of knowledge of diabetes and quality of life; they also performed a walking test and a food interview. Anthropometric assessments and serum chemistry parameters were taken into consideration. Subsequently, they attended 7 lessons on nutrition, diabetes and cardiovascular complications; post intervention, the sample group demonstrated statistically significant improvement in the knowledge of the disease, in anthropometric measurements and walking test. CONCLUSION: Although we have not found an improvement of biochemical parameters, informing diabetic subjects of their health conditions and complications is essential in order to achieve patient empowerment and the compliance.

Neuroprotective agents in the management of glaucoma.

Glaucoma is an optic neuropathy, specifically a neurodegenerative disease characterized by loss of retinal ganglion cells (RGCs) and their axons. The pathogenesis of RGC loss in glaucoma remains incompletely understood and a broad range of possible mechanisms have been implicated. Clinical evidence indicates that lowering intraocular pressure (IOP) does not prevent progression in all patients; therefore, risk factors other than those related to IOP are involved in the disease. The need for alternative, non-IOP-lowering treatments focused at preventing progression, that is, neuroprotectants, has become of interest to both the patient and the physician. Experimental evidence accumulated during the past two decades lend a great deal of support to molecules endowed with neuroprotective features. However, translation to the clinic of the latter drugs results unsuccessful mostly because of the lack of reliable in vivo measure of retinal damage, thus hampering the good therapeutic potential of neuroprotective agents given alone or as adjuvant therapy to IOP-lowering agents. Further research effort is needed to better understand the mechanisms involved in glaucoma and the means to translate into clinic neuroprotective drugs.

Effects of processing on structural, mechanical and biological properties of collagen-based substrates for regenerative medicine.

The aim of this work was to investigate the structural features of type I collagen isoforms and collagen-based films at atomic and molecular scales, in order to evaluate whether and to what extent different protocols of slurry synthesis may change the protein structure and the final properties of the developed scaffolds. Wide Angle X-ray Scattering data on raw materials demonstrated the preferential orientation of collagen molecules in equine tendon-derived collagens, while randomly oriented molecules were found in bovine skin collagens, together with a lower crystalline degree, analyzed by the assessment of FWHM (Full Width at Half Maximum), and a certain degree of salt contamination. WAXS and FT-IR (Fourier Transform Infrared) analyses on bovine collagen-based films, showed that mechanical homogenization of slurry in acidic solution was the treatment ensuring a high content of super-organization of collagen into triple helices and a high crystalline domain into the material. In vitro tests on rat Schwannoma cells showed that Schwann cell differentiation into myelinating cells was dependent on the specific collagen film being used, and was found to be stimulated in case of homogenization-treated samples. Finally DHT/EDC crosslinking treatment was shown to affect mechanical stiffness of films depending on collagen source and processing conditions.

WHO 2016 classification: changes and advancements in the diagnosis of miscellaneous primary CNS tumours.

This short review highlights significant changes and recent findings incorporated to varying extent in the WHO 2016 definition of a variety of tumours, including peripheral nerve sheath tumours, meningiomas, mesenchymal nonmeningothelial tumours, melanocytic tumours, lymphomas and histiocytic tumours, germ cell tumours and non-neuroendocrine pituitary tumours. Most notable classification changes include: adding 'hybrid nerve sheath tumours' to the spectrum of benign nerve sheath tumours; an updated definition of atypical meningioma (WHO grade II), including cases with brain invasion; recognizing dural solitary fibrous tumour (SFT) and haemangiopericytoma (HPC) as a single tumour entity characterized by NAB2 and STAT6 gene fusions for which the term SFT/HPC was chosen; recognizing that pituitary granular cell tumour, spindle cell oncocytoma, and pituicytoma all share nuclear expression of TTF-1, possibly representing a spectrum of a single nosological entity derived from posterior pituitary glial cells. The most significant diagnostic markers which have emerged include: inactivation of NF1, CDKN2A, and PRC2 components, SUZ12 and EED in MPNST, leading to neurofibromin and H3K27me3 expression loss; GNAQ and GNA11 mutations in CNS primary melanocytic tumours; BRAFV600E mutation in histiocytic tumours (Langerhans cell histiocytosis and Erdheim-Chester disease) and papillary craniopharyngioma, which provides both a diagnostic marker in the appropriate pathological setting and a therapeutic target. The WHO 2016 Classification has balanced cutting-edge knowledge on the molecular characteristics of the miscellaneous CNS tumours reviewed here with a practical approach for their daily diagnostic work-up. Much more progress can be expected in the classification of these neoplasms in the near future.

Genetically Defined Oligodendroglioma Is Characterized by Indistinct Tumor Borders at MRI.

BACKGROUND AND PURPOSE: In 2016, the World Health Organization revised the brain tumor classification, making IDH mutation and 1p/19q codeletion the defining features of oligodendroglioma. To determine whether imaging characteristics previously associated with oligodendroglial tumors are still applicable, we evaluated the MR imaging features of genetically defined oligodendrogliomas. MATERIALS AND METHODS: One hundred forty-eight adult patients with untreated World Health Organization grade II and III infiltrating gliomas with histologic oligodendroglial morphology, known 1p/19q status, and at least 1 preoperative MR imaging were retrospectively identified. The association of 1p/19q codeletion with tumor imaging characteristics and ADC values was evaluated. RESULTS: Ninety of 148 (61%) patients had 1p/19q codeleted tumors, corresponding to genetically defined oligodendroglioma, and 58/148 (39%) did not show 1p/19q codeletion, corresponding to astrocytic tumors. Eighty-three of 90 (92%) genetically defined oligodendrogliomas had noncircumscribed borders, compared with 26/58 (45%) non-1p/19q codeleted tumors with at least partial histologic oligodendroglial morphology (P < .0001). Eighty-nine of 90 (99%) oligodendrogliomas were heterogeneous on T1- and/or T2-weighted imaging. In patients with available ADC values, a lower mean ADC value predicted 1p/19q codeletion (P = .0005). CONCLUSIONS: Imaging characteristics of World Health Organization 2016 genetically defined oligodendrogliomas differ from the previously considered characteristics of morphologically defined oligodendrogliomas. We found that genetically defined oligodendrogliomas were commonly poorly circumscribed and were almost always heterogeneous in signal intensity.

Interfibrillar packing of bovine cornea by table-top and synchrotron scanning SAXS microscopy.

Bovine cornea was studied with scanning small-angle X-ray scattering (SAXS) microscopy, by using both synchrotron radiation and a microfocus laboratory source. A combination of statistical (adaptive binning and canonical correlation analysis) and crystallographic (pair distribution function analysis) approaches allowed inspection of the collagen lateral packing of the supramolecular structure. Results reveal (i) a decrease of the interfibrillar distance and of the shell thickness around the fibrils from the periphery to the center of the cornea, (ii) a uniform fibril diameter across the explored area, and (iii) a distorted quasi-hexagonal arrangement of the collagen fibrils. The results are in agreement with existing literature. The overlap between laboratory and synchrotron-radiation data opens new perspectives for further studies on collagen-based/engineered tissues by the SAXS microscopy technique at laboratory-scale facilities.

Blood pressure from childhood to adolescence in obese youths in relation to insulin resistance and asymmetric dimethylarginine.

BACKGROUND AND PROPOSE: Hypertension is the most important cardiovascular complication of obesity, even during childhood. Several studies have demonstrated that there is a natural progression of hypertension from childhood to adulthood. However, there are no data reporting a potential worsening in blood pressure (BP) already moving from the pre-pubertal to the pubertal period in obese youths. The aim of this study was to evaluate early change in BP and its relation to insulin resistance (IR) and asymmetric dimethylarginine (ADMA). METHODS: Thirty obese children underwent a first assessment when they were pre-pubertal (visit_1) and were re-evaluated after a mean of 4.5 years (visit_2). At both visits, anthropometric parameters were assessed, blood samples were collected for measurement of insulin, glucose and ADMA and a 24-h ambulatory BP monitoring was performed. RESULTS: At visit_2, the study participants presented increased HOMA-IR and ADMA compared to visit_1 (HOMA-IR: 3.6 ± 2.8 vs 2.8 ± 1.4, p = 0.01; ADMA: 1.57 ± 0.78 vs 0.77 ± 0.52 µmol/l, p < 0.001). Values of 24-h systolic and diastolic BP SDS (0.86 ± 0.79 vs 0.42 ± 0.83, p = 0.001; -0.45 ± 0.82 vs 0.08 ± 0.51, p = 0.001) were significantly increased at visit_2 compared to visit_1. At both visits, BMI-SDS, HOMA-IR and ADMA were associated with 24-h BP. In addition, over-time changes in IR and ADMA influenced changes in systolic blood pressure and diastolic blood pressure from childhood to adolescence (p < 0.05). CONCLUSIONS: Changes in BP already occur moving from the pre-pubertal to the pubertal period in obese children, and modifications in insulin resistance and ADMA seem to be implicated in this early progression in BP.

An optimized table-top small-angle X-ray scattering set-up for the nanoscale structural analysis of soft matter.

The paper shows how a table top superbright microfocus laboratory X-ray source and an innovative restoring-data algorithm, used in combination, allow to analyze the super molecular structure of soft matter by means of Small Angle X-ray Scattering ex-situ experiments. The proposed theoretical approach is aimed to restore diffraction features from SAXS profiles collected from low scattering biomaterials or soft tissues, and therefore to deal with extremely noisy diffraction SAXS profiles/maps. As biological test cases we inspected: i) residues of exosomes' drops from healthy epithelial colon cell line and colorectal cancer cells; ii) collagen/human elastin artificial scaffolds developed for vascular tissue engineering applications; iii) apoferritin protein in solution. Our results show how this combination can provide morphological/structural nanoscale information to characterize new artificial biomaterials and/or to get insight into the transition between healthy and pathological tissues during the progression of a disease, or to morphologically characterize nanoscale proteins, based on SAXS data collected in a room-sized laboratory.

Three-dimensional coherent diffractive imaging on non-periodic specimens at the ESRF beamline ID10.

The progress of tomographic coherent diffractive imaging with hard X-rays at the ID10 beamline of the European Synchrotron Radiation Facility is presented. The performance of the instrument is demonstrated by imaging a cluster of Fe2P magnetic nanorods at 59 nm 3D resolution by phasing a diffraction volume measured at 8 keV photon energy. The result obtained shows progress in three-dimensional imaging of non-crystalline samples in air with hard X-rays.

Influence of the Mediterranean diet on carotid intima-media thickness in hypercholesterolaemic children: a 12-month intervention study.

BACKGROUND AND AIMS: The Mediterranean diet has been recognised as having a protective role on the cardiovascular system due to its low lipid and high antioxidant content. Lipid profile and oxidant status represent two important risk factors related to endothelial dysfunction, even at early stages of cardiovascular diseases. The aim of the study was to evaluate the influence of a 12-month Mediterranean diet on the variation of lipid profile and carotid intima-media thickness (cIMT) in pre-pubertal hypercholesterolaemic children. METHODS AND RESULTS: We performed a cross-sectional study comparing lipid profile and cIMT in a group of 68 pre-pubertal children (36 with hypercholesterolaemia and 32 controls). In addition, in the hypercholesterolaemic children a 12-month intervention programme with a Mediterranean diet was started to evaluate the variation of lipid profile and cIMT. At baseline, hypercholesterolaemic children showed a significantly higher cIMT (both right and left carotid artery) compared to controls (both p < 0.05). After 12 months of diet intervention, a significant reduction of total cholesterol, LDL-cholesterol and cIMT was documented (all p < 0.05). Furthermore, at the end of follow-up, delta body mass index-Standard Deviation score and delta LDL-cholesterol were significantly and independently related to the changes of cIMT (both p < 0.05). CONCLUSION: The Mediterranean diet represents a valid approach in the treatment of hypercholesterolaemia even during childhood.

Value of IL28B genotyping in patients with HCV-related mixed cryoglobulinemia: results of a large, prospective study.

HCV-related mixed cryoglobulinemia (MC) is characterized by clonal expansion of B cells producing a polyreactive natural antibody (rheumatoid factor) and interferon (IFN)-based therapy is the first therapeutic option in mild-moderate MC. Single nucleotide polymorphisms (SNPs) proximal to genes involved in the innate response (IL28B/IFN-λ gene family) are strongly associated with spontaneous and IFN-induced viral clearance in hepatitis C, but no data exist about their role in HCV-positive MC. A large cohort of patients with HCV and MC was studied to evaluate the influence of IL28B genotype on the response to treatment and/or the evolution to MC of HCV infection. The rs12979860/rs8099917 IL28B polymorphisms were analysed in 481 consecutive HCV-positive subjects (250 with MC and 231 without MC, as controls) using real-time PCR and direct sequencing. Hundred and fifteen HCV patients with MC received standard anti-HCV therapy, and the results were evaluated according to the IL28B SNP distribution. Similar IL28B SNPs allele frequencies were recorded for patients and controls. IL28B major allele homozygosis (for both SNPs tested) was tightly correlated with virological and clinical response (P = 0.002). A statistically significant association was limited to 'difficult-to-treat' (G1/4) HCV genotypes. The IL28B genotype was a strong independent predictor of response (P = 0.007, OR 6.06; CI 1.65-22.22). The IL28B genotype was confirmed to be a useful predictor of response to IFN-based therapy in patients with HCV and MC. The very close correlation between IL28B SNP distribution, virological and clinical response definitively confirmed the key role played by HCV in MC. Conversely, the IL28B genotype does not seem to influence the evolution to MC.