Geographical and temporal distribution of SARS-CoV-2 clades in the WHO European Region, January to June 2020

We show the distribution of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) genetic clades over time and between countries and outline potential genomic surveillance objectives. We applied three genomic nomenclature systems to all sequence data from the World Health Organization European Region available until 10 July 2020. We highlight the importance of real-time sequencing and data dissemination in a pandemic situation, compare the nomenclatures and lay a foundation for future European genomic surveillance of SARS-CoV-2

Hypoxia imaging and theranostic potential of [64Cu][Cu(ATSM)] and ionic Cu(II) salts: a review of current evidence and discussion of the retention mechanisms

Background Tumor hypoxia (low tissue oxygenation) is an adverse condition of the solid tumor environment, associated with malignant progression, radiotherapy resistance, and poor prognosis. One method to detect tumor hypoxia is by positron emission tomography (PET) with the tracer [64Cu][Cu-diacetyl-bis(N(4)-methylthiosemicarbazone)] ([64Cu][Cu(ATSM)]), as demonstrated in both preclinical and clinical studies. In addition, emerging studies suggest using [64Cu][Cu(ATSM)] for molecular radiotherapy, mainly due to the release of therapeutic Auger electrons from copper-64, making [64Cu][Cu(ATSM)] a “theranostic” agent. However, the radiocopper retention based on a metal-ligand dissociation mechanism under hypoxia has long been controversial. Recent studies using ionic Cu(II) salts as tracers have raised further questions on the original mechanism and proposed a potential role of copper itself in the tracer uptake. We have reviewed the evidence of using the copper radiopharmaceuticals [60/61/62/64Cu][Cu(ATSM)]/ionic copper salts for PET imaging of tumor hypoxia, their possible therapeutic applications, issues related to the metal-ligand dissociation mechanism, and possible explanations of copper trapping based on studies of the copper metabolism under hypoxia. Results We found that hypoxia selectivity of [64Cu][Cu(ATSM)] has been clearly demonstrated in both preclinical and clinical studies. Preclinical therapeutic studies in mice have also demonstrated promising results, recently reporting significant tumor volume reductions and improved survival in a dose-dependent manner. Cu(II)-[Cu(ATSM)] appears to be accumulated in regions with substantially higher CD133+ expression, a marker for cancer stem cells. This, combined with the reported requirement of copper for activation of the hypoxia inducible factor 1 (HIF-1), provides a possible explanation for the therapeutic effects of [64Cu][Cu(ATSM)]. Comparisons between [64Cu][Cu(ATSM)] and ionic Cu(II) salts have showed similar results in both imaging and therapeutic studies, supporting the argument for the central role of copper itself in the retention mechanism. Conclusions We found promising evidence of using copper-64 radiopharmaceuticals for both PET imaging and treatment of hypoxic tumors. The Cu(II)-[Cu(ATSM)] retention mechanism remains controversial and future mechanistic studies should be focused on understanding the role of copper itself in the hypoxic tumor metabolism

Quantitative comparison of PET performance-Siemens Biograph mCT and mMR

Background: Integrated clinical whole-body PET/MR systems were introduced in2010. In order to bring this technology into clinical usage, it is of great importance to compare the performance with the well-established PET/CT. The aim of this study was to evaluate PET performance, with focus on image quality, on Siemens BiographmMR (PET/MR) and Siemens Biograph mCT (PET/CT).Methods: A direct quantitative comparison of the performance characteristics between the mMR and mCT system was performed according to National ElectricalManufacturers Association (NEMA) NU 2-2007 protocol. Spatial resolution, sensitivity,count rate and image quality were evaluated. The evaluation was supplementedwith additional standardized uptake value (SUV) measurements. Results: The spatial resolution was similar for the two systems. Average sensitivity was higher for the mMR (13.3 kcps/MBq) compared to the mCT system (10.0 kcps/MBq). Peak noise equivalent count rate (NECR) was slightly higher for the mMR(196 kcps @ 24.4 kBq/mL) compared to the mCT (186 kcps @ 30.1 kBq/mL). Scatterfractions in the clinical activity concentration range yielded lower values for the mCT(34.9 %) compared to those for the mMR (37.0 %). Best image quality of the systems resulted in approximately the same mean hot sphere contrast and a difference of 19 percentage points (pp) in mean cold contrast, in favour of the mCT. In general, point spread function (PSF) increased hot contrast and time of flight (TOF) increased both hot and cold contrast. Highest hot contrast for the smallest sphere (10 mm) was achieved with the combination of TOF and PSF on the mCT. Lung residual error was higher for the mMR (22 %) than that for the mCT (17 %), with no effect of PSF. With TOF, lung residual error was reduced to 8 % (mCT). SUV was accurate for both systems, but PSF caused overestimations for the 13-, 17- and 22-mm spheres. Conclusions: Both systems proved good performance characteristics, and the PETimage quality of the mMR was close to that of the mCT. Differences between the systems were mainly due to the TOF possibility on the mCT, which resulted in an overall better image quality, especially for the most challenging settings with higher background activity and small uptake volumes

Image Quality and Detectability in Siemens Biograph PET/MRI and PET/CT Systems - A Phantom study

Background The technology of modern positron emission tomography (PET) systems continuously improving, and with it the possibility to detect smaller lesions. Since first introduced in 2010, the number of hybrid PET/magnetic resonance imaging (MRI) systems worldwide is constantly increasing. It is therefore important to assess and compare the image quality, in terms of detectability, between the PET/MRI and the well-established PET/computed tomography (CT) systems. For this purpose, a PET image quality phantom (Esser) with hot spheres, ranging from 4 to 20 mm in diameter, was prepared with fluorodeoxyglucose and sphere-to-background activity concentrations of 8:1 and 4:1, to mimic clinical conditions. The phantom was scanned on a PET/MRI and a PET/CT system for both concentrations to obtain contrast recovery coefficients (CRCs) and contrast-to-noise ratios (CNRs), for a range of reconstruction settings. The detectability of the spheres was scored by three human observers for both systems and concentrations and all reconstructions. Furthermore, the impact of acquisition time on CNR and observer detectability was investigated. Results Reconstructions applying point-spread-function modeling (and time-of-flight for the PET/CT) yielded the highest CRC and CNR in general, and PET/CT demonstrated slightly higher values than PET/MRI for most sphere sizes. CNR was dependent on reconstruction settings and was maximized for 2 iterations, a pixel size of less than 2 mm and a 4 mm Gaussian filter. Acquisition times of 97 s (PET/MRI) and 150 s (PET/CT) resulted in similar total net true counts. For these acquisition times, the smallest detected spheres by the human observers in the 8:1 activity concentration was the 6-mm sphere with PET/MRI (CNR = 5.6) and the 5-mm sphere with PET/CT (CNR = 5.5). With an acquisition time of 180 s, the 5-mm sphere was also detected with PET/MRI (CNR = 5.8). The 8-mm sphere was the smallest detected sphere in the 4:1 activity concentration for both systems. Conclusion In this experimental study, similar detectability was found for the PET/MRI and the PET/CT, although for an increased acquisition time for the PET/MRI

Ny subtyp av molluscipoxvirus påvisad : Modern teknik identifierar nya och ovanliga patogener snabbare

Molluscum contagiosum is a viral infection of the epidermis characterized by skin-colored papules or nodules frequently with a central depression. Atypical variants may occur, primarily in immunosuppressed individuals. We here report a case of »giant Molluscum contagiosum« in an immunocompetent child. The patient was presented with a fairly smooth nodule of 2 cm in diameter on the ring finger. Molluscipoxvirus-like virus particles were detected by electron microscopy from the nodule, but since the clinical picture was not compatible with MC, next generation sequencing was performed in order to verify the diagnosis. Of the total number of obtained sequences, 25% belonged to molluscipoxvirus (MCV) and de novo assembly revealed three contigs corresponding to 95% of the MCV genome. The assembled genome was compared to previously published sequences of the »major envelope protein« used for genotyping of MCV genus. Several unique single nucleotide polymorphisms were identified, which led us to classify this virus as a new subtype of MCV

18F-FACBC PET/MRI in the evaluation of human brain metastases: a case report

Abstract Background: Patients with metastatic cancer to the brain have a poor prognosis. In clinical practice, MRI is used to delineate, diagnose and plan treatment of brain metastases. However, MRI alone is limited in detecting micro-metastases, delineating lesions and discriminating progression from pseudo-progression. Combined PET/MRI utilises superior soft tissue images from MRI and metabolic data from PET to evaluate tumour structure and function. The amino acid PET tracer 18F-FACBC has shown promising results in discriminating high- and low-grade gliomas, but there are currently no reports on its use on brain metastases. This is the first study to evaluate the use of 18F-FACBC on brain metastases. Case presentation: A middle-aged female patient with brain metastases was evaluated using hybrid PET/MRI with 18F-FACBC before and after stereotactic radiotherapy, and at suspicion of recurrence. Static/dynamic PET and contrastenhanced T1 MRI data were acquired and analysed. This case report includes the analysis of four 18F-FACBC PET/MRI examinations, investigating their utility in evaluating functional and structural metastasis properties. Conclusion: Analysis showed high tumour-to-background ratios in brain metastases compared to other amino acid PET tracers, including high uptake in a very small cerebellar metastasis, suggesting that 18F-FACBC PET can provide early detection of otherwise overlooked metastases. Further studies to determine a threshold for 18F-FACBC brain tumour boundaries and explore its utility in clinical practice should be performed

Pegs not superior to screws for fixation of fractures of the proximal humerus

Background Angular stable plates were introduced two decades ago as a promising treatment for fixation of displaced fractures of the proximal humerus (PHF). However, high rates of adverse events and reoperations have been reported. One frequent reason is secondary penetration of screws into the glenohumeral joint, due to sinking of the fracture or avascular head necrosis. To prevent joint penetrations angular stable plates with smooth locking pegs instead of locking screws have been developed. The aim of the present study was to investigate whether blunt pegs instead of pointed screws reduced the risk of secondary penetration into the glenohumeral joint during fracture healing after operatively treated PHFs. Methods From two different patient cohorts with displaced PHFs (60 treated with PHILOS plate with screws and 50 with ALPS-PHP plate with pegs), two groups were matched according to fracture type AO/OTA 11-B2 and 11-C2 and age (55–85 years). They were followed up at 3, 6 and 12 months. Primary outcome was radiographic signs of peg or screw penetrations into the glenohumeral joint at 12 months. Secondary outcomes were Oxford shoulder score (OSS) and Constant Score (CS) and radiographic signs of avascular humeral head necrosis (AVN). Results Eighteen PHILOS patients with B2 and C2 fractures could be matched with a corresponding group of 18 operated with ALPS-PHP with pegs. The number of penetrations of pegs and screws were equal between the two groups and the development of avascular head necrosis did not differ either. The functional outcomes for both OSS and CS at 12 months was clearly in favor of patients without joint penetrations in both groups. Conclusion We found no differences in the number of screw or peg penetrations in the PHILOS and ALPS-PHP group and the occurrence of AVN was equal. Joint penetrations led to inferior functional outcomes at 1 year. The ClinicalTrials.gov identifier 20/11/12 prospectively for the Philos Group is NCT01737060, and for the ALPS group 11/03/20 retrospectively is NCT04622852

18F-FACBC PET/MRI in diagnostic assessment and neurosurgery of gliomas

Purpose: This pilot study aimed to evaluate the amino acid tracer 18F-FACBC with simultaneous PET/MRI in diagnostic assessment and neurosurgery of gliomas. Materials and Methods: Eleven patients with suspected primary or recurrent low- or high-grade glioma received an 18F-FACBC PET/MRI examination before surgery. PET and MRI were used for diagnostic assessment, and for guiding tumor resection and histopathological tissue sampling. PET uptake, tumor-to-background ratios (TBRs), time-activity curves, as well as PET and MRI tumor volumes were evaluated. The sensitivities of lesion detection and to detect glioma tissue were calculated for PET, MRI, and combined PET/MRI with histopathology (biopsies for final diagnosis and additional image-localized biopsies) as reference. Results: Overall sensitivity for lesion detection was 54.5% (95% confidence interval [CI], 23.4–83.3) for PET, 45.5% (95% CI, 16.7–76.6) for contrast-enhanced MRI (MRICE), and 100% (95% CI, 71.5–100.0) for combined PET/MRI, with a significant difference between MRICE and combined PET/MRI (P = 0.031). TBRs increased with tumor grade (P = 0.004) and were stable from 10 minutes post injection. PET tumor volumes enclosed most of the MRICE volumes (>98%) and were generally larger (1.5–2.8 times) than the MRICE volumes. Based on image-localized biopsies, combined PET/MRI demonstrated higher concurrence with malignant findings at histopathology (89.5%) than MRICE (26.3%). Conclusions: Low- versus high-grade glioma differentiation may be possible with 18F-FACBC using TBR. 18F-FACBC PET/MRI outperformed MRICE in lesion detection and in detection of glioma tissue. More research is required to evaluate 18F-FACBC properties, especially in grade II and III tumors, and for different subtypes of gliomas.publishedVersio