BackgroundThe roles of asymptomatic hyperuricemia or uric acid (UA) crystals in CKD progression are unknown. Hypotheses to explain links between UA deposition and progression of CKD include that (1) asymptomatic hyperuricemia does not promote CKD progression unless UA crystallizes in the kidney; (2) UA crystal granulomas may form due to pre-existing CKD; and (3) proinflammatory granuloma-related M1-like macrophages may drive UA crystal-induced CKD progression.MethodsMALDI-FTICR mass spectrometry, immunohistochemistry, 3D confocal microscopy, and flow cytometry were used to characterize a novel mouse model of hyperuricemia and chronic UA crystal nephropathy with granulomatous nephritis. Interventional studies probed the role of crystal-induced inflammation and macrophages in the pathology of progressive CKD.ResultsAsymptomatic hyperuricemia alone did not cause CKD or drive the progression of aristolochic acid I-induced CKD. Only hyperuricemia with UA crystalluria due to urinary acidification caused tubular obstruction, inflammation, and interstitial fibrosis. UA crystal granulomas surrounded by proinflammatory M1-like macrophages developed late in this process of chronic UA crystal nephropathy and contributed to the progression of pre-existing CKD. Suppressing M1-like macrophages with adenosine attenuated granulomatous nephritis and the progressive decline in GFR. In contrast, inhibiting the JAK/STAT inflammatory pathway with tofacitinib was not renoprotective.ConclusionsAsymptomatic hyperuricemia does not affect CKD progression unless UA crystallizes in the kidney. UA crystal granulomas develop late in chronic UA crystal nephropathy and contribute to CKD progression because UA crystals trigger M1-like macrophage-related interstitial inflammation and fibrosis. Targeting proinflammatory macrophages, but not JAK/STAT signaling, can attenuate granulomatous interstitial nephritis.

BACKGROUND: The optimal endovascular strategy for reperfusing distal medium-vessel occlusions (DMVO) remains unknown. This study evaluates angiographic and clinical outcomes of thrombectomy strategies in DMVO stroke of the posterior circulation. METHODS: TOPMOST (Treatment for Primary Medium Vessel Occlusion Stroke) is an international, retrospective, multicenter, observational registry of patients treated for DMVO between January 2014 and June 2020. This study analyzed endovascularly treated isolated primary DMVO of the posterior cerebral artery in the P2 and P3 segment. Technical feasibility was evaluated with the first-pass effect defined as a modified Thrombolysis in Cerebral Infarction Scale score of 3. Rates of early neurological improvement and functional modified Rankin Scale scores at 90 days were compared. Safety was assessed by the occurrence of symptomatic intracranial hemorrhage and intervention-related serious adverse events. RESULTS: A total of 141 patients met the inclusion criteria and were treated endovascularly for primary isolated DMVO in the P2 (84.4%, 119) or P3 segment (15.6%, 22) of the posterior cerebral artery. The median age was 75 (IQR, 62–81), and 45.4% (64) were female. The initial reperfusion strategy was aspiration only in 29% (41) and stent retriever in 71% (100), both achieving similar first-pass effect rates of 53.7% (22) and 44% (44; P =0.297), respectively. There were no significant differences in early neurological improvement (aspiration: 64.7% versus stent retriever: 52.2%; P =0.933) and modified Rankin Scale rates (modified Rankin Scale score 0–1, aspiration: 60.5% versus stent retriever 68.6%; P =0.4). In multivariable logistic regression analysis, the time from groin puncture to recanalization was associated with the first-pass effect (adjusted odds ratio, 0.97 [95% CI, 0.95–0.99]; P <0.001) that in turn was associated with early neurological improvement (aOR, 3.27 [95% CI, 1.16–9.21]; P <0.025). Symptomatic intracranial hemorrhage occurred in 2.8% (4) of all cases. CONCLUSIONS: Both first-pass aspiration and stent retriever thrombectomy for primary isolated posterior circulation DMVO seem to be safe and technically feasible leading to similar favorable rates of angiographic and clinical outcome.

The Borna disease virus 1 (BoDV-1) causes severe and often fatal encephalitis in humans. The virus is endemic in parts of Germany, Liechtenstein, Switzerland and Austria. As an increasing number of human BoDV-1 encephalitis cases is being diagnosed, the chance for healthcare professionals to come into contact with infected tissues and bodily fluids from patients with known acute bornavirus encephalitis is also increasing. Therefore, risk assessments are needed. Based on three different incidences of possible exposure to BoDV-1 including an autopsy knife injury, a needlestick injury, and a spill accident with cerebrospinal fluid from patients with acute BoDV-1 encephalitis, we perform risk assessments and review published data. BoDV-1 infection status of the index patient’s tissues and bodily fluids to which contact had occurred should be determined. There is only scarce evidence for possible postexposure prophylaxis, serology, and imaging in healthcare professionals who possibly came into contact with the virus. Despite decade-long laboratory work with BoDV-1, not a single clinically apparent laboratory infection has been published. Given the increasing number of severe or fatal BoDV-1 encephalitis cases, there is a growing need for efficacy-tested, potent antiviral therapeutics against BoDV-1 in humans, both in clinically ill patients and possibly as postexposure prophylaxis in healthcare professionals.

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Magnetic resonance imaging (MRI) is an important imaging modality in stroke. Computer based automated medical image processing is increasingly finding its way into clinical routine. The Ischemic Stroke Lesion Segmentation (ISLES) challenge is a continuous effort to develop and identify benchmark methods for acute and sub-acute ischemic stroke lesion segmentation. Here we introduce an expert-annotated, multicenter MRI dataset for segmentation of acute to subacute stroke lesions (https://doi.org/10.5281/zenodo.7153326). This dataset comprises 400 multi-vendor MRI cases with high variability in stroke lesion size, quantity and location. It is split into a training dataset of n = 250 and a test dataset of n = 150. All training data is publicly available. The test dataset will be used for model validation only and will not be released to the public. This dataset serves as the foundation of the ISLES 2022 challenge (https://www.isles-challenge.org/) with the goal of finding algorithmic methods to enable the development and benchmarking of automatic, robust and accurate segmentation methods for ischemic stroke.

IntroductionDespite sufficient oral anticoagulation (OAC) to prevent cardioembolism, some patients suffer from cerebral ischemic strokes of suspected cardioembolic origin. Reasons for that are not clarified yet. In certain cases, the suspected cardioembolic origin of stroke is questioned. This study aimed to understand the thrombi origin and pathophysiology in patients suffering from stroke despite OAC by the analysis of histologic thrombus composition and imaging characteristics.Materials and MethodsOn two distinct cohorts, we retrospectively analyzed histologic (n = 92) and imaging features (n = 64), i.e., thrombus perviousness in admission CT imaging, of cerebral thrombi retrieved by the endovascular treatment for a large vessel occlusion of the anterior circulation. In each group, patients with non-cardioembolic strokes and suspected cardioembolic strokes with or without anticoagulation were compared.ResultsFibrin/platelet content of suspected cardioembolic thrombi (mean/SD 57.2% ± 13) is higher than in non-cardioembolic thrombi (48.9% ± 17; p = 0.01). In suspected cardioembolic thrombi, the fibrin/platelet content does not differ in the subgroups of patients with (57.3% ± 13) and without prior OAC treatment (56.6% ±13; p = 0.8), both with higher values than non-cardioembolic thrombi. Thrombus perviousness (ε) of suspected cardioembolic OAC thrombi (mean/SD: 0.09 ± 0.06) differs significantly from non-cardioembolic thrombi (0.02 ± 0.02; p &lt; 0.001). Further, ε is higher in suspected cardioembolic thrombi with OAC than in cardioembolic thrombi without OAC (0.06 ± 0.03; p = 0.04) and with insufficient OAC (0.04 ± 0.02; p = 0.07).ConclusionThrombi of the suspected cardioembolic origin of patients with prior OAC do not differ in their histologic composition from those without prior OAC, but both differ from non-cardioembolic thrombi. These histologic results make a non-cardioembolic etiology for strokes despite prior OAC rather unlikely but favor other reasons for these ischemic events. Perviousness assessment reinforces the histologic findings, with additional information about the OAC thrombi, which present with higher perviousness. This suggests that OAC would not affect the relative histologic thrombus composition but may alter the microstructure, as reflected by perviousness.

ObjectivesOpportunistic quantitative computed tomography (oQCT) derived from non-dedicated routine CT has demonstrated high accuracy in diagnosing osteoporosis and predicting incident vertebral fractures (VFs). We aimed to investigate the cost-effectiveness of oQCT screening compared to dual-energy X-ray absorptiometry (DXA) as the standard of care for osteoporosis screening.MethodsThree screening strategies (“no osteoporosis screening”, “oQCT screening”, and “DXA screening”) after routine CT were simulated in a state-transition model for hypothetical cohorts of 1,000 patients (women and men aged 65 years) over a follow-up period of 5 years (base case). The primary outcomes were the cumulative costs and the quality-adjusted life years (QALYs) estimated from a U.S. health care perspective for the year 2022. Cost-effectiveness was assessed based on a willingness-to-pay (WTP) threshold of $70,249 per QALY. The secondary outcome was the number of prevented VFs. Deterministic and probabilistic sensitivity analyses were conducted to test the models’ robustness.ResultsCompared to DXA screening, oQCT screening increased QALYs in both sexes (additional 2.40 per 1,000 women and 1.44 per 1,000 men) and resulted in total costs of $3,199,016 and $950,359 vs. $3,262,934 and $933,077 for women and men, respectively. As a secondary outcome, oQCT screening prevented 2.6 and 2.0 additional VFs per 1,000 women and men, respectively. In the probabilistic sensitivity analysis, oQCT screening remained cost-effective in 88.3% (women) and 90.0% (men) of iterations.ConclusionoQCT screening is a cost-effective ancillary approach for osteoporosis screening and has the potential to prevent a substantial number of VFs if considered in daily clinical practice.