Progression free survival of myeloma patients who become IFE-negative correlates with the detection of residual monoclonal free light chain (FLC) by mass spectrometry.

Deeper responses are associated with improved survival in patients being treated for myeloma. However, the sensitivity of the current blood-based assays is limited. Historical studies suggested that normalisation of the serum free light chain (FLC) ratio in patients who were negative by immunofixation electrophoresis (IFE) was associated with improved outcomes. However, recently this has been called into question. Mass spectrometry (MS)-based FLC assessments may offer a superior methodology for the detection of monoclonal FLC due to greater sensitivity. To test this hypothesis, all available samples from patients who were IFE negative after treatment with carfilzomib and lenalidomide-based induction and autologous stem cell transplantation (ASCT) in the Myeloma XI trial underwent FLC-MS testing. FLC-MS response assessments from post-induction, day+100 post-ASCT and six months post-maintenance randomisation were compared to serum FLC assay results. Almost 40% of patients had discordant results and 28.7% of patients with a normal FLC ratio had residual monoclonal FLC detectable by FLC-MS. FLC-MS positivity was associated with reduced progression-free survival (PFS) but an abnormal FLC ratio was not. This study demonstrates that FLC-MS provides a superior methodology for the detection of residual monoclonal FLC with FLC-MS positivity identifying IFE-negative patients who are at higher risk of early progression.

Modeling the response of Norway spruce tree-ring carbon and oxygen isotopes to selection harvest on a drained peatland forest.

Continuous cover forestry (CCF) has gained interest as an alternative to even-aged management particularly on drained peatland forests. However, relatively little is known about the physiological response of suppressed trees when larger trees are removed as a part of CCF practices. Consequently, studies concentrating on process-level modeling of the response of trees to selection harvesting are also rare. Here, we compared, modeled and measured harvest response of previously suppressed Norway spruce (Picea abies) trees to a selection harvest. We quantified the harvest response by collecting Norway spruce tree-ring samples in a drained peatland forest site and measuring the change in stable carbon and oxygen isotopic ratios of wood formed during 2010-20, including five post-harvest years. The measured isotopic ratios were compared with ecosystem-level process model predictions for ${\kern0em }^{13}$C discrimination and ${\kern0em }^{18}$O leaf water enrichment. We found that the model predicted similar but lower harvest response than the measurements. Furthermore, accounting for mesophyll conductance was important for capturing the variation in ${\kern0em }^{13}$C discrimination. In addition, we performed sensitivity analysis on the model, which suggests that the modeled ${\kern0em }^{13}$C discrimination is sensitive to parameters related to CO2 transport through stomata to the mesophyll.

Drivers of intra-seasonal δ13 C signal in tree-rings of Pinus sylvestris as indicated by compound-specific and laser ablation isotope analysis.

Carbon isotope composition of tree-ring (δ13 CRing ) is a commonly used proxy for environmental change and ecophysiology. δ13 CRing reconstructions are based on a solid knowledge of isotope fractionations during formation of primary photosynthates (δ13 CP ), such as sucrose. However, δ13 CRing is not merely a record of δ13 CP . Isotope fractionation processes, which are not yet fully understood, modify δ13 CP during sucrose transport. We traced, how the environmental intra-seasonal δ13 CP signal changes from leaves to phloem, tree-ring and roots, for 7 year old Pinus sylvestris, using δ13 C analysis of individual carbohydrates, δ13 CRing laser ablation, leaf gas exchange and enzyme activity measurements. The intra-seasonal δ13 CP dynamics was clearly reflected by δ13 CRing , suggesting negligible impact of reserve use on δ13 CRing . However, δ13 CP became increasingly 13 C-enriched during down-stem transport, probably due to post-photosynthetic fractionations such as sink organ catabolism. In contrast, δ13 C of water-soluble carbohydrates, analysed for the same extracts, did not reflect the same isotope dynamics and fractionations as δ13 CP , but recorded intra-seasonal δ13 CP variability. The impact of environmental signals on δ13 CRing , and the 0.5 and 1.7‰ depletion in photosynthates compared ring organic matter and tree-ring cellulose, respectively, are useful pieces of information for studies exploiting δ13 CRing .

Adjudicated myocarditis and multisystem illness trajectory in healthcare workers post-COVID-19.

BACKGROUND: We investigated the associations of healthcare worker status with multisystem illness trajectory in hospitalised post-COVID-19 individuals. METHODS AND RESULTS: One hundred and sixty-eight patients were evaluated 28-60 days after the last episode of hospital care. Thirty-six (21%) were healthcare workers. Compared with non-healthcare workers, healthcare workers were of similar age (51.3 (8.7) years vs 55.0 (12.4) years; p=0.09) more often women (26 (72%) vs 48 (38%); p<0.01) and had lower 10-year cardiovascular risk (%) (8.1 (7.9) vs 15.0 (11.5); p<0.01) and Coronavirus Clinical Characterisation Consortium in-hospital mortality risk (7.3 (10.2) vs 12.7 (9.8); p<0.01). Healthcare worker status associated with less acute inflammation (peak C reactive protein 48 mg/L (IQR: 14-165) vs 112 mg/L (52-181)), milder illness reflected by WHO clinical severity score distribution (p=0.04) and shorter duration of admission (4 days (IQR: 2-6) vs 6 days (3-12)).In adjusted multivariate logistic regression analysis, healthcare worker status associated with a binary classification (probable/very likely vs not present/unlikely) of adjudicated myocarditis (OR: 2.99; 95% CI (1.01 to 8.89) by 28-60 days postdischarge).After a mean (SD, range) duration of follow-up after hospital discharge of 450 (88) days (range 290, 627 days), fewer healthcare workers died or were rehospitalised (1 (3%) vs 22 (17%); p=0.038) and secondary care referrals for post-COVID-19 syndrome were common (42%) and similar to non-healthcare workers (38%; p=0.934). CONCLUSION: Healthcare worker status was independently associated with the likelihood of adjudicated myocarditis, despite better antecedent health. Two in five healthcare workers had a secondary care referral for post-COVID-19 syndrome. TRIAL REGISTRATION NUMBER: NCT04403607.

United Kingdom standards for non-invasive cardiac imaging: recommendations from the Imaging Council of the British Cardiovascular Society.

Heart and circulatory diseases affect more than seven million people in the UK. Non-invasive cardiac imaging is a critical element of contemporary cardiology practice. Progressive improvements in technology over the last 20 years have increased diagnostic accuracy in all modalities and led to the incorporation of non-invasive imaging into many standard cardiac clinical care pathways. Cardiac imaging tests are requested by a variety of healthcare practitioners and performed in a range of settings from the most advanced hospitals to local health centres. Imaging is used to detect the presence and consequences of cardiovascular disease, as well as to monitor the response to therapies. The previous UK national imaging strategy statement which brought together all of the non-invasive imaging modalities was published in 2010. The purpose of this document is to collate contemporary standards developed by the modality-specific professional organisations which make up the British Cardiovascular Society Imaging Council, bringing together common and essential recommendations. The development process has been inclusive and iterative. Imaging societies (representing both cardiology and radiology) reviewed and agreed on the initial structure. The final document therefore represents a position, which has been generated inclusively, presents rigorous standards, is applicable to clinical practice and deliverable. This document will be of value to a variety of healthcare professionals including imaging departments, the National Health Service or other organisations, regulatory bodies, commissioners and other purchasers of services, and service users, i.e., patients, and their relatives.

Cardiovascular magnetic resonance for the detection of descending thoracic aorta calcification in patients with end-stage renal disease.

BACKGROUND: Vascular calcification is an independent predictor of cardiovascular disease in patients with chronic kidney disease. Computed tomography (CT) is the gold-standard for detecting vascular calcification. Radial volumetric-interpolated breath-hold examination (radial-VIBE), a free-breathing gradient-echo cardiovascular magnetic resonance (CMR) sequence, has advantages over CT as it is ionising radiation-free. However, its capability in detecting thoracic aortic calcification (TAC) has not been investigated. This study aims to compare radial-VIBE to CT for the detection of TAC in the descending aorta of patients with end-stage renal disease (ESRD) using semi-automated methods, and to investigate the association between TAC and coronary artery calcification (CAC). METHODS: Paired cardiac CT and radial-VIBE CMR scans from ESRD patients participating in 2 prospective studies were obtained. Calcification volume was quantified using semi-automated methods in a 9 cm segment of the thoracic aorta. Correlation and agreement between TAC volume measured on CMR and CT were assessed with Spearman's correlation coefficient (ρ), linear regression, Bland-Altman plots and intraclass correlation coefficient (ICC). Association between CAC Agatston score and TAC volume determined by CT and CMR was measured with Spearman's correlation coefficient. RESULTS: Scans from 96 participants were analysed. Positive correlation was found between CMR and CT calcification volume [ρ = 0.61, 95% confidence interval (CI) 0.45-0.73]. ICC for consistency was 0.537 (95% CI 0.378-0.665). Bland-Altman plot revealed that compared to CT, CMR volumes were systematically higher at low calcification volume, and lower at high calcification volume. CT did not detect calcification in 41.7% of participants, while radial-VIBE CMR detected signal which the semi-quantitative algorithm reported as calcification in all of those individuals. Instances of suboptimal radial-VIBE CMR image quality were deemed to be the major contributors to the discrepancy. Correlations between CAC Agatston score and TAC volume measured by CT and CMR were ρ = 0.404 (95% CI 0.214-0.565) and ρ = 0.211 (95% CI 0.008-0.396), respectively. CONCLUSION: Radial-VIBE CMR can detect TAC with strong positive association to CT, albeit with the presence of proportional bias. Quantification of vascular calcification by radial-VIBE remains a promising area for future research, but improvements in image quality are necessary.

Access to MRI for patients with cardiac pacemakers and implantable cardioverter defibrillators.

OBJECTIVE: To determine provision of MRI for patients with cardiac implantable electronic devices (CIEDs; pacemakers and defibrillators) in England, to understand regional variation and assess the impact of guideline changes. METHODS: Retrospective data related to MRI scans performed in patients with CIED over the preceding 12 months was collected using a structured survey tool distributed to every National Health Service Trust MRI unit in England. Data were compared with similar data from 2014/2015 and with demand (estimated from local CIED implantation rates and regional population data by sustainability and transformation partnerships (STPs)). RESULTS: Responses were received from 212 of 223 (95%) hospitals in England. 112 (53%) MRI units' scan patients with MR-conditional CIEDs (10% also scan non-MR conditional devices), compared with 46% of sites in 2014/2015. Total annual scan volume increased over fourfold between 2014 and 2019 (1090 to 4896 scans). There was widespread geographical variation, with five STPs (total population >3·5 million representing approximately 25 000 patients with CIED) with no local provision. There was no correlation between local demand (CIED implantation rates) and MRI provision (scan volume). Complication rates were extremely low with three events nationally in 12 months (0·06% CIED-MRI scans). CONCLUSIONS: Provision of MRI for patients with CIEDs in England increased over fourfold in 4 years, but an estimated 10-fold care gap remains. Almost half of hospitals and 1 in 10 STPs have no service, with no relationship between local supply and demand. Availability of MRI for patients with non-MR conditional devices, although demonstrably safe, remains limited.

The ViKTORIES trial: A randomized, double-blind, placebo-controlled trial of vitamin K supplementation to improve vascular health in kidney transplant recipients.

Premature cardiovascular disease and death with a functioning graft are leading causes of death and graft loss, respectively, in kidney transplant recipients (KTRs). Vascular stiffness and calcification are markers of cardiovascular disease that are prevalent in KTR and associated with subclinical vitamin K deficiency. We performed a single-center, phase II, parallel-group, randomized, double-blind, placebo-controlled trial (ISRCTN22012044) to test whether vitamin K supplementation reduced vascular stiffness (MRI-based aortic distensibility) or calcification (coronary artery calcium score on computed tomography) in KTR over 1 year of treatment. The primary outcome was between-group difference in vascular stiffness (ascending aortic distensibility). KTRs were recruited between September 2017 and June 2018, and randomized 1:1 to vitamin K (menadiol diphosphate 5 mg; n = 45) or placebo (n = 45) thrice weekly. Baseline demographics, clinical history, and immunosuppression regimens were similar between groups. There was no impact of vitamin K on vascular stiffness (treatment effect -0.23 [95% CI -0.75 to 0.29] × 10-3  mmHg-1 ; p = .377), vascular calcification (treatment effect -141 [95% CI - 320 to 38] units; p = .124), nor any other outcome measure. In this heterogeneous cohort of prevalent KTR, vitamin K supplementation did not reduce vascular stiffness or calcification over 1 year. Improving vascular health in KTR is likely to require a multifaceted approach.

Research priorities in cardiovascular imaging.

AIM: A modified Delphi approach was used to develop consensus opinion among British Society for Cardiac Imaging/British Society of Cardiac CT (BSCI/BSCCT) members in order to prioritise research questions in cardiovascular imaging. METHODS: All members of the BSCI/BSCCT were invited to submit research questions that they considered to be of the highest clinical and/or academic priority in the field of cardiovascular imaging (phase 1). Subsequently a steering committee removed duplicate questions and combined questions of a similar theme by consensus agreement where appropriate. BSCI/BSCCT members were invited to rank the resulting research questions in two further iterative rounds (phases 2 and 3) to determine a final list of high-priority research questions. RESULTS: A total of 111 research questions were submitted in phase 1 by 30 BSCI/BSCCT members. While there was a broad range of topics, from determining the optimal features/markers of the vulnerable plaque to investigating how cardiac imaging can best be used to maximise clinical outcomes and economic costs, multimodality imaging-related (n=44, 40%) questions dominated the categories and coronary artery imaging (n=40, 36%) was the most common topic. Over two iterative rounds of prioritisation of these research questions, the original 111 were reduced to 75 questions in round 2, and 25 in round 3. From these 25 a final Top 10 list was distilled by consensus grouping. CONCLUSION: This study has identified and ranked the top research priorities in cardiovascular imaging, as identified by the BSCI/BSCCT membership. This is a first step towards identifying the cardiovascular imaging research priorities within the UK and may assist researchers and funding bodies alike in setting priorities.

Multicenter Safety and Practice for Off-Label Diagnostic Use of Ferumoxytol in MRI.

Background Ferumoxytol is approved for use in the treatment of iron deficiency anemia, but it can serve as an alternative to gadolinium-based contrast agents. On the basis of postmarketing surveillance data, the Food and Drug Administration issued a black box warning regarding the risks of rare but serious acute hypersensitivity reactions during fast high-dose injection (510 mg iron in 17 seconds) for therapeutic use. Whereas single-center safety data for diagnostic use have been positive, multicenter data are lacking. Purpose To report multicenter safety data for off-label diagnostic ferumoxytol use. Materials and Methods The multicenter ferumoxytol MRI registry was established as an open-label nonrandomized surveillance databank without industry involvement. Each center monitored all ferumoxytol administrations, classified adverse events (AEs) using the National Cancer Institute Common Terminology Criteria for Adverse Events (grade 1-5), and assessed the relationship of AEs to ferumoxytol administration. AEs related to or possibly related to ferumoxytol injection were considered adverse reactions. The core laboratory adjudicated the AEs and classified them with the American College of Radiology (ACR) classification. Analysis of variance was used to compare vital signs. Results Between January 2003 and October 2018, 3215 patients (median age, 58 years; range, 1 day to 96 years; 1897 male patients) received 4240 ferumoxytol injections for MRI. Ferumoxytol dose ranged from 1 to 11 mg per kilogram of body weight (≤510 mg iron; rate ≤45 mg iron/sec). There were no systematic changes in vital signs after ferumoxytol administration (P > .05). No severe, life-threatening, or fatal AEs occurred. Eighty-three (1.9%) of 4240 AEs were related or possibly related to ferumoxytol infusions (75 mild [1.8%], eight moderate [0.2%]). Thirty-one AEs were classified as allergiclike reactions using ACR criteria but were consistent with minor infusion reactions observed with parenteral iron. Conclusion Diagnostic ferumoxytol use was well tolerated, associated with no serious adverse events, and implicated in few adverse reactions. Registry results indicate a positive safety profile for ferumoxytol use in MRI. © RSNA, 2019 Online supplemental material is available for this article.

Validation of revision data for total hip and knee replacements undertaken at a high volume orthopaedic centre against data held on the National Joint Registry.

BACKGROUND: With over 2.35 million records, the National Joint Registry (NJR) is the largest arthroplasty registry in the world. It provides a powerful tool to monitor implant survivorship and influence different surgical strategies. To date, little work has been undertaken to investigate the validity of the 'Reason for Revision' recorded in Consultant Outcome Reports on the NJR. METHODS: The NJR was queried to identify all revisions on the THR performed at a single centre over an 11-year period. Review and validation of 'Reason for Revision' for each case was undertaken using radiological imaging studies, pathology, histology, microbiology and electronic medical records. RESULTS: Of the 22,046 primary total hip replacements (THR) and total knee replacements (TKR) undertaken by 23 surgeons at our hospital, over an 11-year period, 1.35% (297) were subsequently reported to the NJR as revised. Discrepancies in reporting to the NJR were identified for 41 cases (25.63%) for THR and 28 (20.40%) cases for TKR. Revision for infection was under-reported for both THR and TKR by 1.88% and 3.65% respectively. Reporting of adverse soft tissue reaction to particulate debris for THR was unreported by 11%. Progressive arthritis following a TKR was unreported by 6.56%. All the cases reported as 'other' (8.75% for THRs and 3.65% for TKRs) were reclassified to the most appropriate 'reason for revision' category. The 'reason for revision' data is recorded to the NJR with findings at the time of surgery. It is some days before microbiology and histology reports become available and source data is not always updated. CONCLUSION: If an average of 23% wrong data entry at a highly organised institution is replicated throughout the UK, a formal process to validate primary and revision data submitted to the NJR should be considered. Local scrutiny, review and validation of revision data are all vital to optimise the value of the NJR. Accurate data recorded to the NJR is imperative to provide safe and effective improvements in orthopaedic surgery.

Tree-ring isotopes suggest atmospheric drying limits temperature-growth responses of treeline bristlecone pine.

Altitudinally separated bristlecone pine populations in the White Mountains (California, USA) exhibit differential climate-growth responses as temperature and tree-water relations change with altitude. These populations provide a natural experiment to explore the ecophysiological adaptations of this unique tree species to the twentieth century climate variability. We developed absolutely dated annual ring-width chronologies, and cellulose stable carbon and oxygen isotope chronologies from bristlecone pine growing at the treeline (~3500 m) and ~200 m below for the period AD 1710-2010. These chronologies were interpreted in terms of ecophysiological adaptations to climate variability with a dual-isotope model and a leaf gas exchange model. Ring widths show positive tree growth anomalies at treeline and consistent slower growth below treeline in relation to the twentieth century warming and associated atmospheric drying until the 1980s. Growth rates of both populations declined during and after the 1980s when growing-season temperature and atmospheric vapour pressure deficit continued to increase. Our model-based interpretations of the cellulose stable isotopes indicate that positive treeline growth anomalies prior to the 1980s were related to increased stomatal conductance and leaf-level transpiration and photosynthesis. Reduced growth since the 1980s occurred with a shift to more conservative leaf gas exchange in both the treeline and below-treeline populations, whereas leaf-level photosynthesis continued to increase in response to rising atmospheric CO2 concentrations. Our results suggest that warming-induced atmospheric drying confounds positive growth responses of apparent temperature-limited bristlecone pine populations at treeline. In addition, the observed ecophysiological responses of attitudinally separated bristlecone pine populations illustrate the sensitivity of conifers to climate change.

The effect of precautions on early dislocations post total hip arthroplasty: a retrospective cohort study.

INTRODUCTION: The efficacy of hip precautions in preventing dislocation post total hip arthroplasty (THA) has been questioned in recent literature. From 2014 our centre ceased routinely prescribing them due to lack of evidence. We investigate the effect of stopping these precautions on dislocation rate, patient satisfaction and Oxford hip score (OHS). METHODS: Patients who underwent primary total hip arthroplasty prior to this change in protocol ( n = 2551) and for 1 year subsequently ( n = 673) were identified. Operative records were used to identify key demographic and operative data. Incidence of dislocation, OHS and patient satisfaction were extracted from the centre's electronic database. Subset analysis of those patients dislocating within 6 weeks was performed. RESULTS: Rate of dislocation at 6 weeks in those prescribed and not prescribed precautions was 0.71% and 0.89% respectively ( p = 0.618). At 1 year this rose to 1.25% and 1.49% ( p = 0.406). Satisfaction ( p = 0.332) and OHS ( p = 0.441) at 1 year was not significantly different between cohorts. CONCLUSIONS: Cessation of prescribing routine hip precautions post primary THA does not appear to significantly affect overall dislocation rate, patient satisfaction or functional status at 1 year post-operatively.

Borosilicate Glass Fiber-Optic Biosensor for the Detection of Escherichia coli.

Polyclonal antibodies against Escherichia coli and fluorescent, secondary, antibodies were immobilized on borosilicate glass fibers pre-treated with 3-glycidyloxypropyl trimethoxysilane (GPS). Light with an average wavelength of 627 nm, emitted by a diode placed at one end of the glass fiber, was detected by an ultrasensitive photodiode with peak sensitivity at 640 nm. Changes in fluorescence, caused by binding of E. coli to the antibodies, changed the net refractive index of the glass fiber and thus the internal reflection of light. These evanescent changes in photon energy were recorded by an ultrasensitive photodiode. Signals were amplified and changes in voltage recorded with a digital multimeter. A linear increase in voltage readings was recorded over 2 h when 3.0 × 107 CFU/ml and 2.77 × 109 CFU/ml E. coli were adhered to the antibodies. Voltage readings were recorded with E. coli cell numbers from 2 × 103 CFU/ml to 2 × 106 CFU/ml, but readings remained unchanged for 2 h, indicating that the limit of detection is 3.0 × 107 CFU/ml. This simple technology may be used to develop a low-cost, portable, fiber-optic biosensor to detect E. coli in infections and may have applications in the medical field. Research is in progress to optimize the sensitivity of the fiber-optic biosensor and determine its specificity.

A simple stable carbon isotope method for investigating changes in the use of recent versus old carbon in oak.

Stable carbon isotope ratios from early-wood (EW) and late-wood (LW) are used to test competing models of carbon storage and allocation, providing a cost-effective alternative to measuring and dating non-structural carbohydrates in mature temperate broad-leaf forest trees growing under natural conditions. Annual samples of EW and LW from seven mature oaks (Quercus robur L.) from Scotland, covering AD 1924-2012, were pooled, treated to isolate alpha-cellulose and pyrolysed to measure the carbon isotope ratios. Late-wood values are strongly correlated with summer temperature of the year of growth and EW contains the same signal offset by 1 year. After a warm summer, isotopic ratios of EW are similar to those of the preceding LW, but following cold summers they are relatively enriched. The results conflict with established models of isotopic variation within oak tree rings but support 'two-pool' models for storage of non-structural carbohydrates, with EW formation, which occurs prior to budburst, preferentially using young reserves accumulated in the previous summer. Under poor growing conditions trees access older reserves. Slight average isotopic enrichment of EW may be explained by preferential accumulation of reserves during warmer summers rather than by isotopic enrichment during starch formation in non-photosynthetic tissue.

T1 hyperintensity on brain imaging subsequent to gadolinium-based contrast agent administration: what do we know about intracranial gadolinium deposition?

There is growing evidence for the accumulation of gadolinium (Gd) in patients administered with intravenous Gd-based contrast agents, even in the absence of renal impairment. This review of the literature will discuss what has been found to date in cadaveric human studies, clinical studies of patients and from animal models. Evidence for the potential route of entry into the brain will be examined. The current state of knowledge of effects of Gd accumulation in the brain is discussed. We will then discuss what the possible implications may be for the choice of Gd-based contrast agents in clinical practice.

Non-Contrast Renal Magnetic Resonance Imaging to Assess Perfusion and Corticomedullary Differentiation in Health and Chronic Kidney Disease.

AIMS: Arterial spin labelling (ASL) MRI measures perfusion without administration of contrast agent. While ASL has been validated in animals and healthy volunteers (HVs), application to chronic kidney disease (CKD) has been limited. We investigated the utility of ASL MRI in patients with CKD. METHODS: We studied renal perfusion in 24 HVs and 17 patients with CKD (age 22-77 years, 40% male) using ASL MRI at 3.0T. Kidney function was determined using estimated glomerular filtration rate (eGFR). T1 relaxation time was measured using modified look-locker inversion and xFB02;ow-sensitive alternating inversion recovery true-fast imaging and steady precession was performed to measure cortical and whole kidney perfusion. RESULTS: T1 was higher in CKD within cortex and whole kidney, and there was association between T1 time and eGFR. No association was seen between kidney size and volume and either T1, or ASL perfusion. Perfusion was lower in CKD in cortex (136 ± 37 vs. 279 ± 69 ml/min/100 g; p < 0.001) and whole kidney (146 ± 24 vs. 221 ± 38 ml/min/100 g; p < 0.001). There was significant, negative, association between T1 longitudinal relaxation time and ASL perfusion in both the cortex (r = -0.75, p < 0.001) and whole kidney (r = -0.50, p < 0.001). There was correlation between eGFR and both cortical (r = 0.73, p < 0.01) and whole kidney (r = 0.69, p < 0.01) perfusion. CONCLUSIONS: Significant differences in renal structure and function were demonstrated using ASL MRI. T1 may be representative of structural changes associated with CKD; however, further investigation is required into the pathological correlates of reduced ASL perfusion and increased T1 time in CKD.

3D rotational fluoroscopy for intraoperative clip control in patients with intracranial aneurysms--assessment of feasibility and image quality.

BACKGROUND: Mobile 3D fluoroscopes have become increasingly available in neurosurgical operating rooms. In this series, the image quality and value of intraoperative 3D fluoroscopy with intravenous contrast agent for the evaluation of aneurysm occlusion and vessel patency after clip placement was assessed in patients who underwent surgery for intracranial aneurysms. MATERIALS AND METHODS: Twelve patients were included in this retrospective analysis. Prior to surgery, a 360° rotational fluoroscopy scan was performed without contrast agent followed by another scan with 50 ml of intravenous iodine contrast agent. The image files of both scans were transferred to an Apple PowerMac® workstation, subtracted and reconstructed using OsiriX® free software. The procedure was repeated after clip placement. Both image sets were compared for assessment of aneurysm occlusion and vessel patency. RESULTS: Image acquisition and contrast administration caused no adverse effects. Image quality was sufficient to follow the patency of the vessels distal to the clip. Metal artifacts reduce the assessability of the immediate vicinity of the clip. Precise image subtraction and post-processing can reduce metal artifacts and make the clip-site assessable and depict larger neck-remnants. CONCLUSION: This technique quickly supplies images at adequate quality to evaluate distal vessel patency after aneurysm clipping. Significant aneurysm remnants may be depicted as well. As it does not require visual control of all vessels that are supposed to be evaluated intraoperatively, this technique may be complementary to other intraoperative tools like indocyanine green videoangiography and micro-Doppler, especially for the assessment of larger aneurysms. At the momentary state of this technology, it cannot replace postoperative conventional angiography. However, 3D fluoroscopy and image post-processing are young technologies. Further technical developments are likely to result in improved image quality.

MB3W1 is an orthotopic xenograft model for anaplastic medulloblastoma displaying cancer stem cell- and Group 3-properties.

BACKGROUND: Medulloblastoma is the most common malignant brain tumor in children and can be divided in different molecular subgroups. Patients whose tumor is classified as a Group 3 tumor have a dismal prognosis. However only very few tumor models are available for this subgroup. METHODS: We established a robust orthotopic xenograft model with a cell line derived from the malignant pleural effusions of a child suffering from a Group 3 medulloblastoma. RESULTS: Besides classical characteristics of this tumor subgroup, the cells display cancer stem cell characteristics including neurosphere formation, multilineage differentiation, CD133/CD15 expression, high ALDH-activity and high tumorigenicity in immunocompromised mice with xenografts exactly recapitulating the original tumor architecture. CONCLUSIONS: This model using unmanipulated, human medulloblastoma cells will enable translational research, specifically focused on Group 3 medulloblastoma.