Prenatal MR imaging of dural sinus malformation: a case report

OBJECTIVE: To describe prenatal magnetic resonance imaging (MRI) findings of dural sinus malformation (DSM), a very rare, congenital form of dural arteriovenous shunt (DAVS), typically affecting newborns. METHODS: Ultrasound (US) and MRI were performed at 34 weeks' gestation, and the findings of these examinations were compared with postnatal MRI studies performed at 2 days and 1 month. RESULTS: US showed an anechoic, midline posterior fossa collection with irregular internal echodensities. Color Doppler showed prominent arterial vascularity at the lesion margins. The prenatal MRI showed a large, profoundly hypointense, midline retrocerebellar mass. Postnatal MRI, complemented with magnetic resonance (MR) angiography, showed the lesion to be a giant dural venous pouch fed by multiple mural arteriovenous shunts. Follow-up MRI at 1 month suggested latent venous hypertension and prompted endovascular treatment. CONCLUSION: Prenatal MR imaging is useful to establish the diagnosis, to assess complications such as hydrocephalus and tonsillar prolapse, and to help plan perinatal management, postnatal follow-up, and treatment decision-making.     

A novel homozygous MFN2 mutation associated with severe and atypical CMT2 phenotype

Background

Charcot-Marie-Tooth (CMT) neuropathies represent the most common forms of inherited polyneuropathies. CMT2A, the axonal form, accounts for about one third of all CMT cases. Variants in the MFN2 gene have been recognized to be a major cause of CMT2A. To date, more than 100 pathogenetic mutations in MFN2 have been identified, leading to different neurological clinical spectrum, varying from hereditary neuropathies to more severe clinical phenotypes. Pathogenic variants in MFN2 mainly act in a dominant manner, although in a few sporadic or familial cases, homozygous or compound heterozygous mutations have been reported.

Role of magnetic resonance in characterising extrahepatic cholangiocarcinomas

PURPOSE: The purpose of this study was to evaluate the accuracy of magnetic resonance (MR) in correctly locating and characterising biliary strictures in patients affected by extrahepatic cholangiocarcinoma, identify findings suggestive of the disease, identify lesions with similar MR features and possible criteria for differential diagnosis and establish prospective MR accuracy in diagnosis of malignant obstruction of extrahepatic bile ducts. MATERIALS AND METHODS: We retrospectively reviewed the MR examinations of 39 patients affected by extrahepatic cholangiocarcinoma confirmed by histology or cytology. The studies were evaluated for the following parameters: site of obstruction (hilar, proximal or distal), presence of intra- or extrahepatic dilation of bile ducts, morphology of ductal stenosis (gradual tapering or abrupt ending), morphology of the lesion (mass like or circumferential), dimension, signal intensity before contrast medium administration and lesion enhancement after administration of contrast medium. Finally, we assessed the most useful sequence for the diagnosis. In order to evaluate MR accuracy in the diagnosis of malignant obstruction of extrahepatic bile ducts, we prospectively reviewed MR examinations of 74 patients affected by obstructive jaundice (55 malignant lesions and 19 inflammatory lesions). MR diagnosis was compared with histology or cytology considered as the gold standard. RESULTS: MR allowed identification and localisation of 41/41 extrahepatic cholangiocarcinomas. Fifty-four percent of the lesions showed gradual duct tapering; the remaining lesions showed an abrupt ending. Fifty-six percent of the lesions appeared as a circumferential thickening (infiltrative growth); the remaining lesions had a mass-like appearance (expansile growth). Most lesions were hypo- (49%) or isointense (49%) in T1-weighted sequences and hyper- (49%) or isointense (51%) in T2-weighted sequences. Ninety-five percent of the lesions did not enhance significantly in the arterial phase while 98% showed late enhancement (10 min). The most diagnostic sequence (in 76% of cases) was the late-phase gradient-echo (GRE) T1 fat-saturated sequence. MR had good sensitivity (91%) but poor specificity (47%) in characterising stenosis as malignant, given the large number (10/19) of benign lesions evaluated as neoplastic lesions. CONCLUSIONS: MR almost always identified the cause of stenosis and suggested its neoplastic nature if it exhibited a mass-like appearance (extraductal or growing into the choledochus). On the other hand, lesions with parietal thickening, particularly if smaller than 1 cm, require endoscopic cytology or histology because of the high risk of unnecessary procedures for benign lesions.     

Ability of <Superscript>18</Superscript>F-DOPA PET/CT and fused <Superscript>18</Superscript>F-DOPA PET/MRI to assess striatal involvement in paediatric glioma

Purpose

To assess the diagnostic performance of ¹⁸F-DOPA PET/CT and fused ¹⁸F-DOPA PET/MRI in detecting striatal involvement in children with gliomas.

Methods

This retrospective study included 28 paediatric patients referred to our institution for the presence of primary, residual or recurrent glioma (12 boys, 16 girls; mean age 10.7 years) and investigated with ¹⁸F-DOPA PET/CT and brain MRI. Fused ¹⁸F-DOPA PET/MR images were obtained and compared with PET/CT and MRI images. Accuracy, sensitivity, specificity, negative predictive value (NPV) and positive predictive value (PPV) for striatal involvement were calculated for each diagnostic tool. Univariate and multivariate logistic analyses were applied to evaluate the associations between ¹⁸F-DOPA PET/CT and fused ¹⁸F-DOPA PET/MRI diagnostic results and tumour uptake outside the striatum, grade, dimension and site of striatal involvement (ventral and/or dorsal).

Results

Accuracy, sensitivity, specificity, PPV, and NPV were 100 % for MRI, 93 %, 89 %, 100 %, 100 % and 82 % for ¹⁸F-DOPA PET/MRI, and 75 %, 74 %, 78 %, 88 % and 58 % for ¹⁸F-DOPA PET/CT, respectively. ¹⁸F-DOPA PET/MRI showed a trend towards higher accuracy compared with ¹⁸F-DOPA PET/CT (p?=?0.06). MRI showed significantly higher accuracy compared with ¹⁸F-DOPA PET/CT (p?=?0.01), but there was no significant difference between MRI and ¹⁸F-DOPA PET/MRI. Both univariate and multivariate logistic analyses showed a significant association (OR 8.0 and 7.7, respectively) between the tumour-to-normal striatal uptake (T/S) ratio and the diagnostic ability of ¹⁸F-DOPA PET/CT (p?=?0.03). A strong significant association was also found between involvement of the dorsal striatum and the ¹⁸F-DOPA PET/CT results (p?=?0.001), with a perfect prediction of involvement of the dorsal striatum by ¹⁸F-DOPA PET/MRI.

Conclusion

Physiological striatal ¹⁸F-DOPA uptake does not appear to be a main limitation in the evaluation of basal ganglia involvement.¹⁸F-DOPA PET/CT correctly detected involvement of the dorsal striatum in lesions with a T/S ratio >1, but appeared to be less suitable for evaluation of the ventral striatum. The use of fused ¹⁸F-DOPA PET/MRI further improves the accuracy and is essential for evaluation of the ventral striatum.

     

A risk-benefit assessment of sildenafil in the treatment of erectile dysfunction.

Sildenafil is an oral treatment for erectile dysfunction (ED). It acts as an inhibitor of 3',5'-cyclic guanosine monophosphate-phosphodiesterase type 5. An effective treatment for ED is required to produce an erectile response sufficient for satisfactory sexual performance. This has been documented for sildenafil in men with ED of differing aetiologies and baseline severity in various types of clinical trials. Sildenafil treatment is characterised by a good tolerability profile and low treatment digcontinuation rate caused by treatment-related adverse effects. Most of the adverse effects associated with sildenafil are extensions of the pharmacological action of the drug. There is no significant difference in the adverse effect profile (headache, flushing, dyspepsia, nasal congestion and abnormal vision) of this agent as assessed by clinical data obtained either in the pre- and postlaunch periods. Because of its acceptable risk-benefit ratio, sildenafil can be prescribed to a very large group of patients with ED. The reports of serious cardiovascular events associated with the use of sildenafil (including anecdotal reports of deaths) have been very thoroughly analysed. A number of studies have not shown any difference in the risk of serious cardiovascular events in sildenafil- and placebo-treated patients. However, when making a risk-benefit evaluation, certain subgroups of patients need to be considered separately. In particular, sildenafil is contraindicated in patients receiving nitrate therapy. In some other subgroups of patients, the risks and benefits of treatment need to be assessed on an individual basis and it is hoped that additional data will clarify any possible risks associated with sildenafil administration such patients. It is helpful to compare the risk-benefit profile of sildenafil with the characteristics of other oral drugs for ED. According to the preliminary data, apomorphine and phentolamine are possible future options for the treatment of ED; however, there needs to be further clinical evaluation of these agents. Initial data have shown that sildenafil can be successfully combined with intracavernosal injection in patients nonresponders to either therapy. In conclusion, favourable characteristics make sildenafil suitable for the first-line therapy for a substantial proportion of patients with ED.     

Is there a reason for concern or is it just hype? – A systematic literature review of the clinical consequences of switching from originator biologics to biosimilars

Introduction: While prescribing biosimilars to patients naive to a biologic treatment is a well-accepted practice, switching clinically stable patients from an originator to a biosimilar is an issue for clinicians. Well-designed clinical trials and real-world data which study the consequences of switching from an originator biologic treatment to its biosimilar alternative are limited, especially for monoclonal antibodies.

Areas covered: A systematic literature review was conducted on PubMed to identify evidence of the consequences of switching from original biologics to biosimilars. References of included papers were also scrutinized. After a title-, abstract- and full text screening, out of the 153 original hits and 77 additional ones from screening the references, 58 papers (12 empirical papers, 5 systematic reviews and 41 non-empirical papers) were included.

Expert opinion: Preventing patients on biologic medicines from switching to biosimilars due to anticipated risks seems to be disproportional compared to the expected cost savings and/or improved patient access. Indeed, it is the opinion of the authors that the concern of switching to biosimilars is overhyped.     

Acute hepatitis induced by alpha-interferon in a patient with chronic hepatitis C.

Hepatic adverse effects occur very rarely with alpha-interferon therapy. A case of acute hepatitis induced by alpha-interferon in a 33-year-old man with chronic hepatitis C is described. The patient developed acute hepatitis with very high aminotransferase activity and jaundice. After discontinuing alpha-interferon therapy, hepatitis resolved rapidly. The immune-mediated mechanism is the most probable cause of this hepatitis.     

Direct Wafer-Scale CVD Graphene Growth under Platinum Thin-Films

Since the transfer process of graphene from a dedicated growth substrate to another substrate is prone to induce defects and contamination and can increase costs, there is a large interest in methods for growing graphene directly on silicon wafers. Here, we demonstrate the direct CVD growth of graphene on a SiO₂ layer on a silicon wafer by employing a Pt thin film as catalyst. We pattern the platinum film, after which a CVD graphene layer is grown at the interface between the SiO₂ and the Pt. After removing the Pt, Raman spectroscopy demonstrates the local growth of monolayer graphene on SiO₂. By tuning the CVD process, we were able to fully cover 4-inch oxidized silicon wafers with transfer-free monolayer graphene, a result that is not easily obtained using other methods. By adding Ta structures, local graphene growth on SiO₂ is selectively blocked, allowing the controlled graphene growth on areas selected by mask design.