Prospective Deployment of Deep Learning Reconstruction Facilitates Highly Accelerated Upper Abdominal MRI.

RATIONALE AND OBJECTIVES: To compare a conventional T1 volumetric interpolated breath-hold examination (VIBE) with SPectral Attenuated Inversion Recovery (SPAIR) fat saturation and a deep learning (DL)-reconstructed accelerated VIBE sequence with SPAIR fat saturation achieving a 50 % reduction in breath-hold duration (hereafter, VIBE-SPAIRDL) in terms of image quality and diagnostic confidence. MATERIALS AND METHODS: This prospective study enrolled consecutive patients referred for upper abdominal MRI from November 2023 to December 2023 at a single tertiary center. Patients underwent upper abdominal MRI with acquisition of non-contrast and gadobutrol-enhanced conventional VIBE-SPAIR (fourfold acceleration, acquisition time 16 s) and VIBE-SPAIRDL (sixfold acceleration, acquisition time 8 s) on a 1.5 T scanner. Image analysis was performed by four readers, evaluating homogeneity of fat suppression, perceived signal-to-noise ratio (SNR), edge sharpness, artifact level, lesion detectability and diagnostic confidence. A statistical power analysis for patient sample size estimation was performed. Image quality parameters were compared by a repeated measures analysis of variance, and interreader agreement was assessed using Fleiss' κ. RESULTS: Among 450 consecutive patients, 45 patients were evaluated (mean age, 60 years ± 15 [SD]; 27 men, 18 women). VIBE-SPAIRDL acquisition demonstrated superior SNR (P < 0.001), edge sharpness (P < 0.001), and reduced artifacts (P < 0.001) with substantial to almost perfect interreader agreement for non-contrast (κ: 0.70-0.91) and gadobutrol-enhanced MRI (κ: 0.68-0.87). No evidence of a difference was found between conventional VIBE-SPAIR and VIBE-SPAIRDL regarding homogeneity of fat suppression, lesion detectability, or diagnostic confidence (all P > 0.05). CONCLUSION: Deep learning reconstruction of VIBE-SPAIR facilitated a reduction of breath-hold duration by half, while reducing artifacts and improving image quality. SUMMARY: Deep learning reconstruction of prospectively accelerated T1 volumetric interpolated breath-hold examination for upper abdominal MRI enabled a 50 % reduction in breath-hold time with superior image quality. KEY RESULTS: 1) In a prospective analysis of 45 patients referred for upper abdominal MRI, accelerated deep learning (DL)-reconstructed VIBE images with spectral fat saturation (SPAIR) showed better overall image quality, with better perceived signal-to-noise ratio and less artifacts (all P < 0.001), despite a 50 % reduction in acquisition time compared to conventional VIBE. 2) No evidence of a difference was found between conventional VIBE-SPAIR and accelerated VIBE-SPAIRDL regarding lesion detectability or diagnostic confidence.

Evaluating ChatGPT-4V in chest CT diagnostics: a critical image interpretation assessment.

PURPOSE: To assess the diagnostic accuracy of ChatGPT-4V in interpreting a set of four chest CT slices for each case of COVID-19, non-small cell lung cancer (NSCLC), and control cases, thereby evaluating its potential as an AI tool in radiological diagnostics. MATERIALS AND METHODS: In this retrospective study, 60 CT scans from The Cancer Imaging Archive, covering COVID-19, NSCLC, and control cases were analyzed using ChatGPT-4V. A radiologist selected four CT slices from each scan for evaluation. ChatGPT-4V's interpretations were compared against the gold standard diagnoses and assessed by two radiologists. Statistical analyses focused on accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV), along with an examination of the impact of pathology location and lobe involvement. RESULTS: ChatGPT-4V showed an overall diagnostic accuracy of 56.76%. For NSCLC, sensitivity was 27.27% and specificity was 60.47%. In COVID-19 detection, sensitivity was 13.64% and specificity of 64.29%. For control cases, the sensitivity was 31.82%, with a specificity of 95.24%. The highest sensitivity (83.33%) was observed in cases involving all lung lobes. The chi-squared statistical analysis indicated significant differences in Sensitivity across categories and in relation to the location and lobar involvement of pathologies. CONCLUSION: ChatGPT-4V demonstrated variable diagnostic performance in chest CT interpretation, with notable proficiency in specific scenarios. This underscores the challenges of cross-modal AI models like ChatGPT-4V in radiology, pointing toward significant areas for improvement to ensure dependability. The study emphasizes the importance of enhancing these models for broader, more reliable medical use.

Comparison of the stage-dependent mitochondrial changes in response to pressure overload between the diseased right and left ventricle in the rat.

The right ventricle (RV) differs developmentally, anatomically and functionally from the left ventricle (LV). Therefore, characteristics of LV adaptation to chronic pressure overload cannot easily be extrapolated to the RV. Mitochondrial abnormalities are considered a crucial contributor in heart failure (HF), but have never been compared directly between RV and LV tissues and cardiomyocytes. To identify ventricle-specific mitochondrial molecular and functional signatures, we established rat models with two slowly developing disease stages (compensated and decompensated) in response to pulmonary artery banding (PAB) or ascending aortic banding (AOB). Genome-wide transcriptomic and proteomic analyses were used to identify differentially expressed mitochondrial genes and proteins and were accompanied by a detailed characterization of mitochondrial function and morphology. Two clearly distinguishable disease stages, which culminated in a comparable systolic impairment of the respective ventricle, were observed. Mitochondrial respiration was similarly impaired at the decompensated stage, while respiratory chain activity or mitochondrial biogenesis were more severely deteriorated in the failing LV. Bioinformatics analyses of the RNA-seq. and proteomic data sets identified specifically deregulated mitochondrial components and pathways. Although the top regulated mitochondrial genes and proteins differed between the RV and LV, the overall changes in tissue and cardiomyocyte gene expression were highly similar. In conclusion, mitochondrial dysfuntion contributes to disease progression in right and left heart failure. Ventricle-specific differences in mitochondrial gene and protein expression are mostly related to the extent of observed changes, suggesting that despite developmental, anatomical and functional differences mitochondrial adaptations to chronic pressure overload are comparable in both ventricles.

Image Quality and Diagnostic Performance of Accelerated 2D Hip MRI with Deep Learning Reconstruction Based on a Deep Iterative Hierarchical Network.

OBJECTIVES: Hip MRI using standard multiplanar sequences requires long scan times. Accelerating MRI is accompanied by reduced image quality. This study aimed to compare standard two-dimensional (2D) turbo spin echo (TSE) sequences with accelerated 2D TSE sequences with deep learning (DL) reconstruction (TSEDL) for routine clinical hip MRI at 1.5 and 3 T in terms of feasibility, image quality, and diagnostic performance. MATERIAL AND METHODS: In this prospective, monocentric study, TSEDL was implemented clinically and evaluated in 14 prospectively enrolled patients undergoing a clinically indicated hip MRI at 1.5 and 3T between October 2020 and May 2021. Each patient underwent two examinations: For the first exam, we used standard sequences with generalized autocalibrating partial parallel acquisition reconstruction (TSES). For the second exam, we implemented prospectively undersampled TSE sequences with DL reconstruction (TSEDL). Two radiologists assessed the TSEDL and TSES regarding image quality, artifacts, noise, edge sharpness, diagnostic confidence, and delineation of anatomical structures using an ordinal five-point Likert scale (1 = non-diagnostic; 2 = poor; 3 = moderate; 4 = good; 5 = excellent). Both sequences were compared regarding the detection of common pathologies of the hip. Comparative analyses were conducted to assess the differences between TSEDL and TSES. RESULTS: Compared with TSES, TSEDL was rated to be significantly superior in terms of image quality (p ≤ 0.020) with significantly reduced noise (p ≤ 0.001) and significantly improved edge sharpness (p = 0.003). No difference was found between TSES and TSEDL concerning the extent of artifacts, diagnostic confidence, or the delineation of anatomical structures (p > 0.05). Example acquisition time reductions for the TSE sequences of 52% at 3 Tesla and 70% at 1.5 Tesla were achieved. CONCLUSION: TSEDL of the hip is clinically feasible, showing excellent image quality and equivalent diagnostic performance compared with TSES, reducing the acquisition time significantly.

Shaping a suitable EU HTA dossier template: why the German template is not fit for purpose.

From 2025, Health Technology Developers (HTDs) have to submit EU HTA dossiers. The joint clinical assessment (JCA) aims to streamline HTA processes and access to medicinal products across Europe. Currently, German HTA bodies IQWiG and G-BA actively shape the JCA methodology. Here we examine if German HTA dossier requirements are suitable for the JCA. We compare the number of safety endpoint and subgroup analyses in German dossiers with analyses considered in IQWIG's benefit assessment and evaluate if these analyses were considered by the G-BA. We further investigated how the number of analyses was affected by the latest change in the German dossier template. With the current template, HTDs report in median 2.6 times more analyses on adverse events (AE) and 1.1 times more subgroup categories than in the previous template. IQWiG does not consider 33% of AE analyses and 73% of the subgroup categories presented by the HTD under the current template. G-BA considered the same AE as IQWiG in 76% of cases. Subgroups were uncommented by G-BA in most cases, independent of the template (previous: 93%, current 85%) and unconsidered in the conclusion on additional benefit (previous: 77%, current 69%). Thus, changes in the dossier template drastically increased HTD workload, but additional analyses seem unconsidered by the HTA bodies. With a broader scope in JCA, this effect could be amplified. To mitigate duplicative efforts and ensure prompt availability of medicinal products as envisioned by the HTAR, we suggest well-chosen and precise dossier requirements, early consultations, and early HTD engagement.

Faster Elbow MRI with Deep Learning Reconstruction-Assessment of Image Quality, Diagnostic Confidence, and Anatomy Visualization Compared to Standard Imaging.

OBJECTIVE: The objective of this study was to evaluate a deep learning (DL) reconstruction for turbo spin echo (TSE) sequences of the elbow regarding image quality and visualization of anatomy. MATERIALS AND METHODS: Between October 2020 and June 2021, seventeen participants (eight patients, nine healthy subjects; mean age: 43 ± 16 (20-70) years, eight men) were prospectively included in this study. Each patient underwent two examinations: standard MRI, including TSE sequences reconstructed with a generalized autocalibrating partial parallel acquisition reconstruction (TSESTD), and prospectively undersampled TSE sequences reconstructed with a DL reconstruction (TSEDL). Two radiologists evaluated the images concerning image quality, noise, edge sharpness, artifacts, diagnostic confidence, and delineation of anatomical structures using a 5-point Likert scale, and rated the images concerning the detection of common pathologies. RESULTS: Image quality was significantly improved in TSEDL (mean 4.35, IQR 4-5) compared to TSESTD (mean 3.76, IQR 3-4, p = 0.008). Moreover, TSEDL showed decreased noise (mean 4.29, IQR 3.5-5) compared to TSESTD (mean 3.35, IQR 3-4, p = 0.004). Ratings for delineation of anatomical structures, artifacts, edge sharpness, and diagnostic confidence did not differ significantly between TSEDL and TSESTD (p > 0.05). Inter-reader agreement was substantial to almost perfect (κ = 0.628-0.904). No difference was found concerning the detection of pathologies between the readers and between TSEDL and TSESTD. Using DL, the acquisition time could be reduced by more than 35% compared to TSESTD. CONCLUSION: TSEDL provided improved image quality and decreased noise while receiving equal ratings for edge sharpness, artifacts, delineation of anatomical structures, diagnostic confidence, and detection of pathologies compared to TSESTD. Providing more than a 35% reduction of acquisition time, TSEDL may be clinically relevant for elbow imaging due to increased patient comfort and higher patient throughput.

Enhanced Image Processing Using Complex Averaging in Diffusion-Weighted Imaging of the Prostate: The Impact on Image Quality and Lesion Detectability.

Diffusion-weighted images of the prostate can suffer from a "hazy" background in low signal-intensity areas. We hypothesize that enhanced image processing (EIP) using complex averaging reduces artifacts, noise, and distortion in conventionally acquired diffusion-weighted images and synthesized high b-value images, thus leading to higher image quality and better detection of potentially malignant lesions. Conventional DWI trace images with a b-value of 1000 s/mm2 (b1000), calculated images with a b-value of 2000 s/mm2 (cb2000), and ADC maps of 3T multiparametric prostate MRIs in 53 patients (age 68.8 ± 10 years) were retrospectively evaluated. Standard images were compared to images using EIP. In the standard images, 36 lesions were detected in the peripheral zone and 20 in the transition zone. In 13 patients, EIP led to the detection of 8 additional lesions and the upgrading of 6 lesions; 6 of these patients were diagnosed with prostate carcinoma Gleason 7 or 8. EIP improved qualitative ratings for overall image quality and lesion detectability. Artifacts were significantly reduced in the cb2000 images. Quantitative measurements for lesion detectability expressed as an SI ratio were significantly improved. EIP using complex averaging led to image quality improvements in acquired and synthesized DWI, potentially resulting in elevated diagnostic accuracy and management changes.

Influence of [18F]FDG-PET/CT on Clinical Management Decisions in Breast Cancer Patients-A PET/CT Registry Study.

There is a lack of evidence regarding the clinical impact of [18F]fluorodeoxyglucose positron emission tomography/computed tomography ([18F]FDG-PET/CT, hereinafter referred to as PET/CT), especially regarding management changes and their link to overall survival. We analyzed 52 PET/CTs in 47 stage I-IV breast cancer patients, selected from a prospective oncological PET/CT registry. Indications for PET/CT were primary staging (n = 15), restaging (n = 17), and suspected recurrence (n = 20). PET/CT-induced management changes were categorized as major or minor. PET/CT-induced management changes in 41 of 52 scans (78.8%; 38 of 47 patients (80.9%)), of which major changes were suggested in 18 of 52 scans (34.6%, 17 of 47 patients, 36.2%). PET/CT downstaged 6 of 15 primary staging patients, excluding distant metastases. Major management changes were documented in 3 of 17 restaging exams. PET/CT ruled out clinically suspected recurrence in 6 of 20 cases and confirmed it in 11 of 20. In three cases, locoregional recurrence had already been diagnosed via biopsy. In 30 of 52 exams, additional diagnostic tests were avoided, of which 13 were invasive. PET/CT-based management changes resulted in a 5-year survival rate of 72.3% for the whole study group, 93.3% for the staging group, 53.8% for the restaging group, and 68.4% for the recurrence group. This study shows that PET/CT significantly impacts clinical management decisions in breast cancer patients in different clinical scenarios, potentially determining the patient's tumor stage as the basis for further therapy more reliably and by avoiding unnecessary diagnostic tests.

A transient increase of HIF-1α during the G1 phase (G1-HIF) ensures cell survival under nutritional stress.

The family of hypoxia-inducible transcription factors (HIF) is activated to adapt cells to low oxygen conditions, but is also known to regulate some biological processes under normoxic conditions. Here we show that HIF-1α protein levels transiently increase during the G1 phase of the cell cycle (designated as G1-HIF) in an AMP-activated protein kinase (AMPK)-dependent manner. The transient elimination of G1-HIF by a degron system revealed its contribution to cell survival under unfavorable metabolic conditions. Indeed, G1-HIF plays a key role in the cell cycle-dependent expression of genes encoding metabolic regulators and the maintenance of mTOR activity under conditions of nutrient deprivation. Accordingly, transient elimination of G1-HIF led to a significant reduction in the concentration of key proteinogenic amino acids and carbohydrates. These data indicate that G1-HIF acts as a cell cycle-dependent surveillance factor that prevents the onset of starvation-induced apoptosis.

Deep Learning MRI Reconstruction for Accelerating Turbo Spin Echo Hand and Wrist Imaging: A Comparison of Image Quality, Visualization of Anatomy, and Detection of Common Pathologies with Standard Imaging.

RATIONALE AND OBJECTIVES: Magnetic resonance imaging (MRI) of the hand and wrist is a routine MRI examination and takes about 15-20 minutes, which can lead to problems resulting from the relatively long scan time, such as decreased image quality due to motion artifacts and lower patient throughput. The objective of this study was to evaluate a deep learning (DL) reconstruction for turbo spin echo (TSE) sequences of the hand and wrist regarding image quality, visualization of anatomy, and diagnostic performance concerning common pathologies. MATERIALS AND METHODS: Twenty-one patients (mean age: 43 ± 19 [19-85] years, 10 men, 11 female) were prospectively enrolled in this study between October 2020 and June 2021. Each participant underwent two MRI protocols: first, standard fully sampled TSE sequences reconstructed with a standard GRAPPA reconstruction (TSES) and second, prospectively undersampled TSE sequences using a conventional parallel imaging undersampling pattern reconstructed with a DL reconstruction (TSEDL). Both protocols were acquired consecutively in one examination. Two experienced MSK-imaging radiologists qualitatively evaluated the images concerning image quality, noise, edge sharpness, artifacts, and diagnostic confidence, as well as the delineation of anatomical structures (triangular fibrocartilage complex, tendon of the extensor carpi ulnaris muscle, extrinsic and intrinsic ligaments, median nerve, cartilage) using a five-point Likert scale and assessed common pathologies. Wilcoxon signed-rank test and kappa statistics were performed to compare the sequences. RESULTS: Overall image quality, artifacts, delineation of anatomical structures, and diagnostic confidence of TSEDL were rated to be comparable to TSES (p > 0.05). Additionally, TSEDL showed decreased image noise (4.90, median 5, IQR 5-5) compared to TSES (4.52, median 5, IQR 4-5, p < 0.05) and improved edge sharpness (TSEDL: 4.10, median 4, IQR 3.5-5; TSES: 3.57, median 4, IQR 3-4; p < 0.05). Inter- and intrareader agreement was substantial to almost perfect (κ = 0.632-1.000) for the detection of common pathologies. Time of acquisition could be reduced by more than 60% with the protocol using TSEDL. CONCLUSION: Compared to TSES, TSEDL provided decreased noise and increased edge sharpness, equal image quality, delineation of anatomical structures, detection of pathologies, and diagnostic confidence. Therefore, TSEDL may be clinically relevant for hand and wrist imaging, as it reduces examination time by more than 60%, thus increasing patient comfort and patient throughput.

Impact of HPV mRNA types 16, 18, 45 detection on the risk of CIN3+ in young women with normal cervical cytology.

BACKGROUND: Despite a well-established cervical cancer (CC) screening program in Norway, the incidence of CC in young women is increasing, peaking at 35 years of age. 25 percent of all women diagnosed with CC had normal cytology within 3 years prior to cancer diagnosis, addressing the need to improve the screening programme to further reduce cancer incidences missed by cytology. OBJECTIVE: We wanted to investigate the detection rate of CIN3+ in women 25-39 years with normal cytology by using a 3-type HPV mRNA test as a targeted quality assurance measure. The control group is women with normal cytology. METHODS: During 2014-2017, samples from 13,021 women 25-39 years of age attending cervical cancer screening were analysed at Nordlandssykehuset, Bodø, Norway, including 1,896 women with normal cytology and HPV mRNA test (intervention group), and 11,125 women with cytology only (control group). The HPV mRNA testing was performed using a 3-type HPV E6/E7 mRNA test (PreTect SEE; direct genotyping 16, 18 and 45). The women were followed-up according to national guidelines throughout December 2021. RESULTS: Of the 13,021 women, 429 women (3.3%) had CIN3+ confirmed by biopsy in the follow-up, including 13 cases of invasive cervical cancer. Of the 1,896 women with normal cytology and HPV mRNA test (intervention group), 49 women (2.6%) had a positive test. The risks of CIN3+ among women with either a positive or negative HPV mRNA test were 28.6% (14/49) and 0.8% (14/1847). None of the women in the intervention group developed cervical cancer during follow-up. Of the 11,125 women with cytology only (control group), 712 women (6.4%) had abnormal cytology (ASC-US+). The risks of CIN3+ among women with abnormal and normal cytology were 17.7% (126/712) and 2.6% (275/10,413). CONCLUSION: By testing women 25-39 years of age with a normal cytology result using a specific 3-type HPV mRNA test, an increase in screening programme sensitivity can be achieved without an excessive additional workload. Women with normal cytology and a negative HPV mRNA test have a very low risk of cervical cancer.

Successful repair of an outflow graft twisting of Heartmate II left ventricular assist device: a case report.

An outflow graft obstruction impairing the blood flow is a complication of a left ventricular assist device therapy due to thrombosis as the most common cause. We describe a rare case of a patient who presented with a new low-flow alarm after 7 years of uneventful left ventricular assist device support with Heartmate II device. Computed tomography and surgical exploration revealed an obstruction caused by a twist of the outflow graft. A successful surgical repair without the use of cardiopulmonary bypass could be performed and resulted in immediate relief of symptoms.

Dual-energy CT based monitoring of treatment-induced bone marrow changes in lung cancer patients: preliminary results.

Background: Systemic lung cancer treatment-induced changes in bone marrow attenuation assessed via dual-energy CT-based virtual non-calcium (VNCa) imaging of the axial skeleton and their relationship to hematological laboratory have not yet been investigated. Methods: VNCa bone marrow images of the axial skeleton derived from 93 unenhanced reduced dose dual-energy CTs of the thorax and abdomen of 31 patients were retrospectively analyzed. Each patient had received one pre-therapy baseline exam and two consecutive follow-up exams (FU1 and FU2) at a mean of 7.7 and 11.7 weeks after start of therapy. Concurrent hematologic laboratory data were available for every exam. Seven regions of interest were placed in the spine and pelvis and mean VNCa bone marrow attenuation was measured. Twenty-two Patients receiving highly myelotoxic treatment (Group A) were compared to 9 patients receiving less toxic substances (Group B). Results: Median bone marrow attenuation in Group A/Group B was -31.8 HU (IQR 12.7)/40.6 HU (IQR, 12.2) at baseline, -46.5 HU (IQR, 12.5)/-43.8 HU (15.7) at FU1 and -46.9 HU (IQR, 22.0)/-38.5 HU (IQR, 18.5) at FU2. In both subgroups the reduction of the mean attenuation between baseline and FU1 was statistically significant although in Group A it was more pronounced; no significant difference was found between FU1 and FU2. The differences between Groups were not statistically significant. Leukopenia rates at FU1 and FU 2 were 50% and 54.5% in Group A and 0% and 22% in Group B. Anemia rates rose from 31.8% at baseline to 90% at FU1 and 86.4% at FU2 in Group A and fell from 77.8% at baseline to 66.7% at FU1 and further to 55.6% at FU2 in Group B. Conclusions: Both highly myelotoxic as well as-to a smaller degree-less myelotoxic systemic therapy led to a significant drop in bone marrow attenuation with no significant tendency towards subsequent elevation irrespective of the treatment's degree of toxicity or the presence of myelosuppression and not even under hematological supportive therapy. The results suggest that in this clinical setting an increase in bone marrow attenuation should be regarded as suspicious for tumor infiltration.

Dual-Energy CT-Based Bone Marrow Imaging in Multiple Myeloma: Assessment of Focal Lesions in Relation to Disease Status and MRI Findings.

RATIONALE AND OBJECTIVES: To assess focal multiple myeloma bone lesions via dual-energy CT-based virtual noncalcium (VNCa) bone marrow imaging in relation to the overall hematological disease status and MRI findings. MATERIALS AND METHODS: We retrospectively evaluated 103 focal osteolytic lesions of the axial skeleton in VNCa bone marrow images of 32 patients. Region of interest-based attenuation measurements were correlated with T1w signal intensity and apparent diffusion coefficient (ADC). Results were compared between patients in active and inactive disease. Receiver operating characteristic analysis was performed to determine a cut-off value of VNCa attenuation for differentiation between the two groups. Standard of reference was the overall disease status according to International Myeloma Working Group response criteria. RESULTS: Mean attenuation difference between lesions and background bone marrow was significantly lower in inactive disease (16 HU, SD 30) compared to active disease (35 HU, SD 29). VNCa attenuation measurement allowed for differentiation between active and inactive disease with a sensitivity of 92% and a specificity of 58% at a cut-off value of -21 HU. VNCa attenuation was negatively correlated to T1w signal intensity (Spearman's ρ -0.617, p < 0.001) and positively correlated to ADC (Spearman's ρ 0.521, p < 0.001). CONCLUSION: Quantitative assessment of attenuation of focal osteolytic lesions in VNCa bone marrow images allows differentiation between overall active and inactive disease with higher attenuation signifying an increasing likelihood of active disease. This is supported by a significant positive correlation between the attenuation and the ADC, as well as a corresponding inverse correlation to T1w signal intensity.

Genauigkeit und Reproduzierbarkeit eines Software-Prototypen zur halbautomatischen computergestützten Volumetrie der soliden und subsoliden Komponenten von teilsoliden Lungenrundherden.

PURPOSE: To test the accuracy and reproducibility of a software prototype for semi-automated computer-aided volumetry (CAV) of part-solid pulmonary nodules (PSN) with separate segmentation of the solid part. MATERIALS AND METHODS: 66 PSNs were retrospectively identified in 34 thin-slice unenhanced chest CTs of 19 patients. CAV was performed by two medical students. Manual volumetry (MV) was carried out by two radiology residents. The reference standard was determined by an experienced radiologist in consensus with one of the residents. Visual assessment of CAV accuracy was performed. Measurement variability between CAV/MV and the reference standard as a measure of accuracy, CAV inter- and intra-rater variability as well as CAV intrascan variability between two recontruction kernels was determined via the Bland-Altman method and intraclass correlation coefficients (ICC). RESULTS: Subjectively assessed accuracy of CAV/MV was 77 %/79 %-80 % for the solid part and 67 %/73 %-76 % for the entire nodule. Measurement variability between CAV and the reference standard ranged from -151-117 % for the solid part and -106-54 % for the entire nodule. Interrater variability was -16-16 % for the solid part (ICC 0.998) and -102-65 % for the entire nodule (ICC 0.880). Intra-rater variability was -70-49 % for the solid part (ICC 0.992) and -111-31 % for the entire nodule (ICC 0.929). Intrascan variability between the smooth and the sharp reconstruction kernel was -45-39 % for the solid part and -21-46 % for the entire nodule. CONCLUSION: Although the software prototype delivered satisfactory results when segmentation is evaluated subjectively, quantitative statistical analysis revealed room for improvement especially regarding the segmentation accuracy of the solid part and the reproducibility of measurements of the nodule's subsolid margins. KEY POINTS: · Assessed visually CAV delivers similar accuracy compared to manual volumetry. · Accuracy of CAV was higher for the entire nodule. · Reproducibility was better for the solid part. · Variability between the kernels was higher for the solid part.

Towards compatibility of EUnetHTA JCA methodology and German HTA: a systematic comparison and recommendations from an industry perspective.

OBJECTIVE: The transferability of the EU joint clinical assessment (JCA) reports for pharmaceuticals for the German benefit assessment was evaluated by systematically comparing EU JCA and German clinical assessments (CA) based on established assessment elements for HTA and assessing the potential impact of differences on Federal Joint Committee (Gemeinsamer Bundesausschuss, G-BA) ability to derive the therapeutic added value. METHODS: Identification of all pharmaceuticals undergoing both, EU JCA and German CA between January 2016-June 2020. Qualitative review and data extraction from the assessments, assessment of methodological differences using a hierarchical model. Recommendations for harmonisation were developed and consented with pharmaceutical industry stakeholders. RESULTS: Differences with potentially major impact: (1) View on differing treatment algorithms and definition of corresponding subpopulations/respective comparators. (2) Clinical relevance of surrogate/intermediate endpoints. Inclusion of different/surrogate morbidity endpoints resulting in different relative effectiveness conclusions. (3) Tolerance of study interventions not used according to marketing authorisation. (4) Different operationalisation and/or weighting of individual safety endpoints leading to differing relative safety conclusions. Differences with potentially minor impact: (1) Disagreement in risk of bias assessment for overall survival and its robustness against study limitations. (2) Use of patient-reported outcome symptom scales as measurements for health-related quality of life instruments. CONCLUSION: While many synergies between EU JCA and German CA exist, we identified several aspects in HTA methodology that would benefit of harmonisation and ensure the transferability of future EU JCA to the German HTA process without duplicated evaluation requirements. For those, a set of recommendations was developed.

H2 S Dosimetry by CuO: Towards Stable Sensors by Unravelling the Underlying Solid-State Chemistry.

The precise detection of the toxic gas H2 S requires reliable sensitivity and specificity of sensors even at minute concentrations of as low as 10 ppm, the value corresponding to typical exposure limits. CuO can be used for H2 S dosimetry, based on the formation of conductive CuS and the concomitant significant increase in conductance. In theory, at elevated temperature the reaction is reversed and CuO is formed, ideally enabling repeated and long-term use of one sensor. Yet, the performance of CuO tends to drop upon cycling. Utilizing defined CuO nanorods we thoroughly elucidated the associated detrimental chemical changes directly on the sensors, by Raman and electron microscopy analysis of each step during sensing (CuO→CuS) and regeneration (CuS→CuO) cycles. We find the decrease in the sensing performance is mainly caused by the irreversible formation of CuSO4 during regeneration. The findings allowed us to develop strategies to reduce CuSO4 formation and thus to substantially maintain the sensing stability even for repeated cycles. We achieved CuO-based dosimeters possessing a response time of a few minutes only, even for 10 ppm H2 S, and prolonged life-time.

COVID-19 among children seeking primary paediatric care with signs of an acute infection.

AIM: It can be challenging to distinguish COVID-19 in children from other common infections. We set out to determine the rate at which children consulting a primary care paediatrician with an acute infection are infected with SARS-CoV-2 and to compare distinct findings. METHOD: In seven out-patient clinics, children aged 0-13 years with any new respiratory or gastrointestinal symptoms and presumed infection were invited to be tested for SARS-CoV-2. Factors that were correlated with testing positive were determined. Samples were collected from 25 January 2021 to 01 April 2021. RESULTS: Seven hundred and eighty-three children participated in the study (median age 3 years and 0 months, range 1 month to 12 years and 11 months). Three hundred and fifty-eight were female (45.7%). SARS-CoV-2 RNA was detected in 19 (2.4%). The most common symptoms in children with as well as without detectable SARS-CoV-2 RNA were rhinitis, fever and cough. Known recent exposure to a case of COVID-19 was significantly correlated with testing positive, but symptoms or clinical findings were not. CONCLUSION: COVID-19 among the children with symptoms of an acute infection was uncommon, and the clinical presentation did not differ significantly between children with and without evidence of an infection with SARS-CoV-2.

Comprehensive Characterization of a Mesoporous Cerium Oxide Nanomaterial with High Surface Area and High Thermal Stability.

In the present study, the pore space of a mesoporous cerium oxide material is investigated, which forms by the self-assembly of primary particles into a spherical secondary structure possessing a disordered mesopore space. The material under study exhibits quite stable mesoporosity upon aging at high temperatures (800 °C) and is, thus, of potential interest in high-temperature catalysis. Here, different characterization techniques were applied to elucidate the structural evolution taking place between heat treatment at 400 °C and aging at 800 °C, i.e., in a water-containing atmosphere, which is usually detrimental to nanoscaled porosity. The changes in the mesoporosity were monitored by advanced physisorption experiments, including hysteresis scanning, and electron tomography analysis coupled with a 3D reconstruction of the mesopore space. These methods indicate that the 3D spatial arrangement of the primary particles during the synthesis under hydrothermal conditions via thermal hydrolysis is related to the thermal stability of the hierarchical mesopore structure. The assembly of the primary CeO2 particles (∼4 nm in size) results in an interparticulate space constituting an open 3D mesopore network, as revealed by skeleton analysis of tomography data, being in conformity with hysteresis scanning. At elevated temperatures (800 °C), sinter processes occur resulting in the growth of the primary particles, but the 3D mesopore network and the spherical secondary structure are preserved.