Tick-borne encephalitis virus (TBEV) prevalence in field-collected ticks (Ixodes ricinus) and phylogenetic, structural and virulence analysis in a TBE high-risk endemic area in southwestern Germany

Background Tick-borne encephalitis (TBE) is the most common viral CNS infection with incidences much higher than all other virus infections together in many risk areas of central and eastern Europe. The Odenwald Hill region (OWH) in southwestern Germany is classified as a TBE risk region and frequent case numbers but also more severe infections have been reported within the past decade. The objective of the present study was to survey the prevalence of tick-borne encephalitis virus (TBEV) in Ixodes ricinus and to associate TBEV genetic findings with TBE infections in the OWH. Methods Ticks were collected by the flagging methods supported by a crowdsourcing project implementing the interested public as collectors to cover completely and collect randomly a 3532 km2 area of the OWH TBE risk region. Prevalence of TBEV in I. ricinus was analysed by reversed transcription quantitative real-time PCR. Phylogeographic analysis was performed to classify OWH TBEV isolates within a European network of known TBEV strains. Mutational sequence analysis including 3D modelling of envelope protein pE was performed and based on a clinical database, a spatial association of TBE case frequency and severity was undertaken. Results Using the crowd sourcing approach we could analyse a total of 17,893 ticks. The prevalence of TBEV in I. ricinus in the OWH varied, depending on analysed districts from 0.12% to 0% (mean 0.04%). Calculated minimum infection rate (MIR) was one decimal power higher. All TBEV isolates belonged to the European subtype. Sequence analysis revealed a discontinuous segregation pattern of OWH isolates with two putative different lineages and a spatial association of two isolates with increased TBE case numbers as well as exceptional severe to fatal infection courses. Conclusions TBEV prevalence within the OWH risk regions is comparatively low which is probably due to our methodological approach and may more likely reflect prevalence of natural TBEV foci. As for other European regions, TBEV genetics show a discontinuous phylogeny indicating among others an association with bird migration. Mutations within the pE gene are associated with more frequent, severe and fatal TBE infections in the OWH risk region

Compressed SENSE accelerated 3D single-breath-hold late gadolinium enhancement cardiovascular magnetic resonance with isotropic resolution: clinical evaluation

AimThe purpose of this study was to investigate the clinical application of Compressed SENSE accelerated single-breath-hold LGE with 3D isotropic resolution compared to conventional LGE imaging acquired in multiple breath-holds.Material & MethodsThis was a retrospective, single-center study including 105 examinations of 101 patients (48.2 ± 16.8 years, 47 females). All patients underwent conventional breath-hold and 3D single-breath-hold (0.96 × 0.96 × 1.1 mm3 reconstructed voxel size, Compressed SENSE factor 6.5) LGE sequences at 1.5 T in clinical routine for the evaluation of ischemic or non-ischemic cardiomyopathies. Two radiologists independently evaluated the left ventricle (LV) for the presence of hyperenhancing lesions in each sequence, including localization and transmural extent, while assessing their scar edge sharpness (SES). Confidence of LGE assessment, image quality (IQ), and artifacts were also rated. The impact of LV ejection fraction (LVEF), heart rate, body mass index (BMI), and gender as possible confounders on IQ, artifacts, and confidence of LGE assessment was evaluated employing ordinal logistic regression analysis.ResultsUsing 3D single-breath-hold LGE readers detected more hyperenhancing lesions compared to conventional breath-hold LGE (n = 246 vs. n = 216 of 1,785 analyzed segments, 13.8% vs. 12.1%; p < 0.0001), pronounced at subendocardial, midmyocardial, and subepicardial localizations and for 1%–50% of transmural extent. SES was rated superior in 3D single-breath-hold LGE (4.1 ± 0.8 vs. 3.3 ± 0.8; p < 0.001). 3D single-breath-hold LGE yielded more artifacts (3.8 ± 1.0 vs. 4.0 ± 3.8; p = 0.002) whereas IQ (4.1 ± 1.0 vs. 4.2 ± 0.9; p = 0.122) and confidence of LGE assessment (4.3 ± 0.9 vs. 4.3 ± 0.8; p = 0.374) were comparable between both techniques. Female gender negatively influenced artifacts in 3D single-breath-hold LGE (p = 0.0028) while increased heart rate led to decreased IQ in conventional breath-hold LGE (p = 0.0029).ConclusionsIn clinical routine, Compressed SENSE accelerated 3D single-breath-hold LGE yields image quality and confidence of LGE assessment comparable to conventional breath-hold LGE while providing improved delineation of smaller LGE lesions with superior scar edge sharpness. Given the fast acquisition of 3D single-breath-hold LGE, the technique holds potential to drastically reduce the examination time of CMR

Clinical outcome and cerebrospinal fluid profiles in patients with tick-borne encephalitis and prior vaccination history

Background: Tick-borne encephalitis (TBE) is endemic in southern and eastern districts of Germany. Approximately 10–14% of the infected individuals suffer from long-term disability and in 1.5–3.6% the course is fatal. Two well-tolerated vaccines are available, which provide high protection and which have been confirmed in several field studies. Here we investigate clinical course, long-term outcome and cerebrospinal fluid (CSF) characteristics of TBE cases with a prior history of any vaccination as well as real vaccination breakthrough (VBT). Methods: A case series of 11 patients with a prior history of vaccination, part of a recently published lager cohort of 111 TBE cases. Evaluation included clinical data, degree of disability (modified RANKIN scale, mRS) and analysis of CSF and serum samples. Furthermore, metadata for extended analysis on clinical outcome of TBE with VBT were analysed. Results: One patient had a clear VBT and ten of them had irregular vaccinations schedules (IVS). Infection severity did not differ in patients with IVS as compared to a non-vaccinated control cohort (median mRS: both 3.0) but these patients showed a stronger cellular immune response as measured by CSF pleocytosis (IVS, 205 cells/μL versus non-vaccinated control, 114 cell/μL, P < 0.05) and by differential pattern of CSF (intrathecal) immunoglobulin synthesis. However, shift analysis of VBT metadata using linear-by-linear association revealed a more serious course of TBE in patients with VBT than in a non-vaccinated control cohort (χ2 = 9.95, P = 0.002). Furthermore, ordinal logistic regression analysis showed that VBT patients had an age-corrected, 2.65 fold (CI: 1.110–6.328; χ2 = 4.813; p = 0.028) significant higher risk to suffer from moderate or severe infections, respectively. Conclusion: A history of IVS surprisingly seems to have no impact on the clinical course of TBE but may leave marks in the specific brain immune response. VBT patients, however, carry an age-independent, significant risk to experience a severe infection

Predictors, neuroimaging characteristics and long-term outcome of severe european tick-borne encephalitis: a prospective cohort study

Background and Objectives: Tick-borne encephalitis (TBE) still represents a considerable medical and health economic problem in Europe and entails a potential threat to travellers. The aim of this study was to characterise the conditions of severe TBE by precisely recording its clinical variants, the related neuroimaging features, and the variant-specific long-term outcome and by identifying predictors for severe courses. Methods: A cohort of 111 TBE patients (median age 51, range 17–75 years; 42% females) was analysed prospectively. Data were acquired from the department of neurology, University Hospital Heidelberg, and the infectious diseases registry of the Robert-Koch institute Berlin. Neurological status was ascertained by protocol at admission and discharge and the degree of disability was scored using the modified RANKIN Scale (mRS; clinical score addressing neurological disability, range from 0, healthy to 6, dead) at admission and at follow-up. Follow-up examination was conducted by means of a telephone interview. To identify independent predictors for severe TBE and functional outcome, modelled logistic regression was performed. MRI changes were correlated with infection variants. To assess alpha-motor neuron injury patterns, we used high resolution magnetic resonance neurography (hrMRN). Analyses were performed at the Department of Neurology, University Hospital, University of Heidelberg from April 2004 through September 2014 Results: Acute course: 3.6% of patients died during the acute infection. All patients with a lethal course suffered from meningoencephaloradiculitis (MER, 14.4% of the cohort), which is associated with a significantly higher risk of requiring intensive care (p = 0.004) and mechanical ventilation (p<0.001) than menigoencephalitis (ME, 27.9% of the cohort). At admission, both MER and ME groups were severely affected, with the MER group having a statistically higher mRS score (median of 5 in the MER groups versus 4 in the ME group; p<0.001). Long-term outcome: outcome for MER was considerably worse (median mRS = 4) than for ME (mRS = 1, p<0.0001) and meningitis (mRS = 0, 57.7% of the cohort). Risk factors: advanced age (p<0.001) and male gender (p = 0.043) are independent risk factors for a severe infection course. Furthermore, we identified pre-existing diabetes mellitus (p = 0.024) as an independent risk factor for MER. In MER, alpha-motor neuron injury accounts for the poor prognosis confirmed by hrMRN. Conclusion and Relevance: These data provide critical information for neurologists and other health professionals to use in evaluating TBEV patients who live in or travel to endemic areas. This information can be used to classify clinical presentation and estimate infection-associated complications and individual prognosis. Furthermore, the risk for severe, disabling infections in older patients should prompt general practitioners to recommend and encourage vaccination to those patients living in or travelling to endemic areas

Propensity score-adjusted analysis on stent-assisted coiling versus coiling alone for ruptured intracranial aneurysms

Stent-assisted coiling (SAC) for ruptured intracranial aneurysms (RIAs) remains controversial due to an inherent risk of potential thromboembolic and hemorrhagic complications. We compared SAC and coiling alone for the management of RIAs using propensity score-adjustment. Sixty-four patients treated by SAC and 220 by stand-alone coiling were retrospectively reviewed and compared using inverse probability of treatment weighting (IPTW) with propensity scores. Functional outcome, procedure-related and overall complications and angiographic results were analyzed. Aneurysms treated by SAC had a larger diameter, a wider neck and were more frequently located at the posterior circulation. SAC had a higher risk for thromboembolic complications (17.2% vs. 7.7%, p = 0.025), however, this difference did not persist in the IPTW analysis (OR 1.2, 95% CI 0.7-2.3, adjusted p = 0.458). In the adjusted analysis, rates of procedural cerebral infarction (p = 0.188), ventriculostomy-related hemorrhage (p = 0.584), in-hospital mortality (p = 0.786) and 6-month favorable functional outcome (p = 0.471) were not significantly different between the two groups. SAC yielded a higher complete occlusion (80.0% vs. 67.2%, OR 3.2, 95% CI 1.9-5.4, p < 0.001) and a lower recanalization rate (17.5% vs. 26.1%, OR 0.3, 95% CI 0.2-0.6, p < 0.001) than stand-alone coiling at 6-month follow-up. In conclusion, SAC of large and wide-necked RIAs provided higher aneurysm occlusion and similar clinical outcome, when compared to stand-alone coiling

Virtual monoenergetic images and post-processing algorithms effectively reduce CT artifacts from intracranial aneurysm treatment

To evaluate artifact reduction by virtual monoenergetic images (VMI) and metal artifact reduction algorithms (MAR) as well as the combination of both approaches (VMIMAR) compared to conventional CT images (CI) as standard of reference. In this retrospective study, 35 patients were included who underwent spectral-detector CT (SDCT) with additional MAR-reconstructions due to artifacts from coils or clips. CI, VMI, MAR and VMIMAR (range: 100-200keV, 10keV-increment) were reconstructed. Region-of-interest based objective analysis was performed by assessing mean and standard deviation of attenuation (HU) in hypo- and hyperdense artifacts from coils and clips. Visually, extent of artifact reduction and diagnostic assessment were rated. Compared to CI, VMI >= 100keV, MAR and VMIMAR between 100-200keV increased attenuation in hypoattenuating artifacts (CI/VMI200keV/MAR/VMIMAR200keV, HU: -77.6 +/- 81.1/-65.1 +/- 103.2/-36.9 +/- 27.7/-21.1 +/- 26.7) and decreased attenuation in hyperattenuating artifacts (HU: 47.4 +/- 32.3/42.1 +/- 50.2/29.5 +/- 18.9/20.8 +/- 25.8). However, differences were only significant for MAR in hypodense and VMIMAR in hypo- and hyperdense artifacts (p= 140/100keV, MAR and VMIMAR >= 100keV. Diagnostic assessment of surrounding brain tissue was significantly improved in VMI >= 100keV, MAR and VMIMAR >= 100keV. The combination of VMI and MAR facilitates a significant reduction of artifacts adjacent to intracranial coils and clips. Hence, if available, these techniques should be combined for optimal reduction of artifacts following intracranial aneurysm treatment

Obesity-Related Pitfalls of Virtual versus True Non-Contrast Imaging—An Intraindividual Comparison in 253 Oncologic Patients

Objectives: Dual-source dual-energy CT (DECT) facilitates reconstruction of virtual non-contrast images from contrast-enhanced scans within a limited field of view. This study evaluates the replacement of true non-contrast acquisition with virtual non-contrast reconstructions and investigates the limitations of dual-source DECT in obese patients. Materials and Methods: A total of 253 oncologic patients (153 women; age 64.5 ± 16.2 years; BMI 26.6 ± 5.1 kg/m2) received both multi-phase single-energy CT (SECT) and DECT in sequential staging examinations with a third-generation dual-source scanner. Patients were allocated to one of three BMI clusters: non-obese: 2 (n = 110), pre-obese: 25–29.9 kg/m2 (n = 73), and obese: >30 kg/m2 (n = 70). Radiation dose and image quality were compared for each scan. DECT examinations were evaluated regarding liver coverage within the dual-energy field of view. Results: While arterial contrast phases in DECT were associated with a higher CTDIvol than in SECT (11.1 vs. 8.1 mGy; p p 2 = 0.738) and SECT (R2 = 0.620); however, DLP of SECT showed a stronger increase in obese patients (p < 0.001). Incomplete coverage of the liver within the dual-energy field of view was most common in the obese subgroup (17.1%) compared with non-obese (0%) and pre-obese patients (4.1%). Conclusion: DECT facilitates a 30.8% dose reduction over SECT in abdominal oncologic staging examinations. Employing dual-source scanner architecture, the risk for incomplete liver coverage increases in obese patients

Evaluation of equivocal small cystic pancreatic lesions with spectral-detector computed tomography

Background Evaluation of small cystic lesions of the pancreas remains a challenging task, as due to their size appearance can be rather hypodense than clearly fluid-filled. Purpose To evaluate whether additional information provided by novel dual-layer spectral-detector computed tomography (SDCT) imaging can improve assessment of these lesions. Material and Methods For this retrospective study, we reviewed reports of 1192 contrast-enhanced portal-venous phase SDCT scans of the abdomen conducted between May 2017 and January 2019. On basis of the radiological report 25 small (<= 1.5 cm) cystic pancreatic lesions in 22 patients were identified, in which additional short-term follow-up imaging was recommended to confirm/clarify cystic nature. Conventional images (CI) and spectral images (SI) including virtual-monoenergetic images at 40 keV (VMI), iodine-density and iodine-overlay images were reconstructed. Two readers indicated lesion conspicuity and confidence for presence of cystic nature on three-point scales. First, solely CI were evaluated, while in a second reading after a four-week interval, the combination of CI and corresponding SI were reviewed. Quantitatively, ROI-based mean attenuation was measured in CI and VMI. Results In the subjective reading, SI significantly improved lesion conspicuity (CI 2 [1-2], SI 3 [2-3], P < 0.001) and confidence regarding presence of cystic nature (CI 2 [1-2], SI 3 [3-3], P < 0.001). Inter-observer agreement depicted by intraclass correlation coefficient improved considerably from 0.51 with only CI to 0.85 when the combination with SI was used. Further, VMI displayed significantly higher signal-to-noise (CI 1.2 +/- 0.8, VMI 3.2 +/- 1.8, P < 0.001) and contrast-to-noise ratios (CI 2.6 +/- 0.8, VMI 4.7 +/- 1.9). Conclusion Compared to CI alone, combination with SI significantly improves visualization and confidence in evaluation of small equivocal cystic pancreatic lesions

Assessing the scapholunate and lunotriquetral interosseous ligament in MR arthrography: Diagnostic advantages of paraxial reformatting

Purpose: The scapholunate (SLIL) and lunotriquetral interosseous ligament (LTIL) function as the main stabilizers of the proximal carpal row. Even with MR arthrography, component assessability is often limited in orthogonal standard planes due to their horseshoe-like shape and resulting partial volume effects. This study aims to investigate the diagnostic value of reformatting isotropic 3D sequences with respect to the anatomical orientation of the intrinsic carpal ligaments. Method: In 110 MR arthrograms of the wrist, we investigated the diagnostic accuracy of two radiologists (R1/R2) for SLIL and LTIL injuries in orthogonal standard planes vs. ancillary angulated reformatting of isotropic 3D dual echo steady state sequence. Component assessability and diagnostic confidence were compared between datasets. Results: The addition of paraxial reformations improved diagnostic accuracy for lesions of the palmar (R1: 0.87 vs. 0.93; R2: 0.86 vs. 0.93; all p < 0.05) and dorsal LTIL (R1: 0.85 vs. 0.93; R2: 0.82 vs. 0.90; all p < 0.05). No significant increase in accuracy could be ascertained for palmar (R1: 0.92 vs. 0.94, p = 0.50; R2: 0.86 vs. 0.92, p = 0.07) and dorsal (R1: 0.95 vs. 0.95, p = 1.00; R2: 0.90 vs. 0.94, p = 0.29) lesions of the SLIL. Interrater reliability was almost perfect with and without angulated planes for SLIL (Kappa = 0.88 vs. 0.82) and LTIL assessment (Kappa = 0.88 vs. 0.86). For the LTIL, observer confidence and component assessability were superior with anatomical reformations available (all p < 0.05). Conclusions: In contrast to SLIL injuries, diagnosis of LTIL lesions benefits from ancillary paraxial reformations of 3D sequences in MR wrist arthrography