Impact of different image reconstructions on PET quantification in non-small cell lung cancer: a comparison of adenocarcinoma and squamous cell carcinoma

OBJECTIVE: Positron emission tomography (PET) using 18F-fluordeoxyglucose (F-FDG) is an established imaging modality for tumor staging in patients with non-small cell lung cancer (NSCLC). There is a growing interest in using F-FDG PET for therapy response assessment in NSCLC which relies on quantitative PET parameters such as standardized uptake values (SUV). Different reconstruction algorithms in PET may affect SUV. We sought to determine the variation of SUV in patients with NSCLC when using ordered subset expectation maximization (OSEM) and block sequential regularized expectation maximization (BSREM) in latest-generation digital PET/CT, including a subanalysis for adenocarcinoma and squamous cell carcinoma. METHODS: A total of 58 patients (34 = adenocarcinoma, 24 = squamous cell carcinoma) that underwent a clinically indicated F-FDG PET/CT for staging were reviewed. PET images were reconstructed with OSEM and BSREM reconstruction with noise penalty strength β-levels of 350, 450, 600, 800 and 1200. Lung tumors maximum standardized uptake value (SUV) were compared. RESULTS: Lung tumors SUV were significantly lower in adenocarcinomas compared to squamous cell carcinomas in all reconstructions evaluated (all p 0.05). There was a statistically significant difference of the relative increase of SUV in adenocarcinoma (mean + 34.8%) and squamous cell carcinoma (mean 23.4%), when using BSREM instead of OSEM (p < 0.05). CONCLUSIONS: In NSCLC the relative change of SUV when using BSREM instead of OSEM is significantly higher in adenocarcinoma as compared to squamous cell carcinoma. ADVANCES IN KNOWLEDGE: The impact of BSREM on SUV may vary in different histological subtypes of NSCLC. This highlights the importance for careful standardisation of β-value used for serial F-FDG PET scans when following-up NSCLC patients

Zurich Consensus: Statement of German Experts on St. Gallen Conference 2011 on Primary Breast Cancer (Zurich 2011)

Every 2 years, the International Consensus Conference on the Treatment of Primary Breast Cancer takes place in St. Gallen. Given that the concept of the St. Gallen Consensus Conference mainly reflects an international opinion, it appears useful to adapt the results of the vote for everyday therapy in Germany. A German working group comprising 28 breast cancer experts, amongst whom there are 3 members of the international St. Gallen panel, has therefore commented on this year's St. Gallen Consensus Conference (2011) from the German viewpoint. The focus of interest of this year's St. Gallen Conference was tumour biology as the starting point for decisions regarding individual therapy. There was an intensive discussion in relation to the clinical relevance of predictive and prognostic factors and possible consequences for decisions regarding therapy. Therefore, questions concerning the indication for adjuvant chemotherapy focused especially on the significance of the molecular phenotype of the tumour. In addition, important points for discussion were also the value of complete axillary dissection and the use of accelerated complete breast irradiation

Capturing a Flavivirus Pre-Fusion Intermediate

During cell entry of flaviviruses, low endosomal pH triggers the rearrangement of the viral surface glycoproteins to a fusion-active state that allows the release of the infectious RNA into the cytoplasm. In this work, West Nile virus was complexed with Fab fragments of the neutralizing mAb E16 and was subsequently exposed to low pH, trapping the virions in a pre-fusion intermediate state. The structure of the complex was studied by cryo-electron microscopy and provides the first structural glimpse of a flavivirus fusion intermediate near physiological conditions. A radial expansion of the outer protein layer of the virion was observed compared to the structure at pH 8. The resulting ∼60 Å-wide shell of low density between lipid bilayer and outer protein layer is likely traversed by the stem region of the E glycoprotein. By using antibody fragments, we have captured a structural intermediate of a virus that likely occurs during cell entry. The trapping of structural transition states by antibody fragments will be applicable for other processes in the flavivirus life cycle and delineating other cellular events that involve conformational rearrangements

Reducing Intravenous Narcotic Documentation Errors On the Electronic Anesthesia Record: A Quality Improvement Project

Medication errors are an important public health problem with high human and financial costs. Medication errors in anesthesia can result in patient morbidity or mortality and should be preventable.  Evidence in the literature supports increasing computer access to reduce the number of medication errors. The purpose of this study was to determine if medication errors could be reduced in one university hospital through a clinical intervention of increasing computer access in the post-anesthesia care unit. A quantitative retrospective chart review was conducted. A statistical test of two independent proportions was used to examine the occurrence of schedule II (fentanyl) and IV (midazolam) controlled substance documentation errors before and after increasing computer access in the post-anesthesia care unit. Access to computers appeared to be associated with a reduction of medication errors from 2.3% to 1.5%. The compliance rate increased from 97.6% to 98.5%. The reduction in the error percentage was significant (z = 2.045, p = 0.04). Our findings provide objective evidence for the support of continuous process improvement to reduce medication errors in anesthesia

Diagnostic Value of Fully Automated Artificial Intelligence Powered Coronary Artery Calcium Scoring from 18F-FDG PET/CT

OBJECTIVES The objective of this study was to assess the feasibility and accuracy of a fully automated artificial intelligence (AI) powered coronary artery calcium scoring (CACS) method on ungated CT in oncologic patients undergoing 18F-FDG PET/CT. METHODS A total of 100 oncologic patients examined between 2007 and 2015 were retrospectively included. All patients underwent 18F-FDG PET/CT and cardiac SPECT myocardial perfusion imaging (MPI) by 99mTc-tetrofosmin within 6 months. CACS was manually performed on non-contrast ECG-gated CT scans obtained from SPECT-MPI (i.e., reference standard). Additionally, CACS was performed using a cloud-based, user-independent tool (AI-CACS) on ungated CT scans from 18F-FDG-PET/CT examinations. Agatston scores from the manual CACS and AI-CACS were compared. RESULTS On a per-patient basis, the AI-CACS tool achieved a sensitivity and specificity of 85% and 90% for the detection of CAC. Interscore agreement of CACS between manual CACS and AI-CACS was 0.88 (95% CI: 0.827, 0.918). Interclass agreement of risk categories was 0.8 in weighted Kappa analysis, with a reclassification rate of 44% and an underestimation of one risk category by AI-CACS in 39% of cases. On a per-vessel basis, interscore agreement of CAC scores ranged from 0.716 for the circumflex artery to 0.863 for the left anterior descending artery. CONCLUSIONS Fully automated AI-CACS as performed on non-contrast free-breathing, ungated CT scans from 18F-FDG-PET/CT examinations is feasible and provides an acceptable to good estimation of CAC burden. CAC load on ungated CT is, however, generally underestimated by AI-CACS, which should be taken into account when interpreting imaging findings

Galaxy Group at z=0.3 Associated with the Damped Lyman Alpha System Towards Quasar Q1127-145

(Abridged) We performed a spectroscopic galaxy survey, complete to m<20.3 (L_B>0.15L_B* at z=0.3), within 100x100" of the quasar Q1127-145 (z=1.18). The VLT/UVES quasar spectrum contains three z<0.33 MgII absorption systems. We obtained eight new galaxy redshifts, adding to the four previously known, and galaxy star formation rates and metallicities were computed where possible. A strong MgII system [W_r(2796)=1.8A], which is a known DLA, had three previously identified galaxies; we found two additional galaxies associated with this system. These five galaxies form a group with diverse properties, such as a luminosity range of 0.04<L_B<0.63L_B*, an impact parameter range of 17<D<241kpc and velocity dispersion of 115km/s. The DLA group galaxy redshifts span beyond the 350km/s velocity spread of the metallic absorption lines of the DLA itself. The two brightest group galaxies have SFRs of a few Msun/yr and should not have strong winds. We have sufficient spectroscopic information to directly compare three of the five group galaxies' (emission-line) metallicities with the DLA (absorption) metallicity: the DLA metallicity is 1/10th solar, substantially lower than the three galaxies' which range between less than 1/2 solar to solar metallicity. HST/WFPC-2 imaging shows perturbed morphologies for the three brightest group galaxies, with tidal tails extending 25kpc. We favor a scenario where the DLA absorption originates from tidal debris in the group environment. Another absorber exhibits weak MgII absorption [W_r(2796)=0.03A] and had a previously identified galaxy at a similar redshift. We have identified a second galaxy associated with this system. Both galaxies have solar metallicities and unperturbed morphologies. The SFR of one galaxy is much lower than expected for strong outflows. Finally, we have identified five galaxies at large impact parameters with no associated MgII absorption.Comment: 15 pages, 7 figures, 5 tables. Accepted for publication in MNRAS

Progranulin signaling in sepsis, community-acquired bacterial pneumonia and COVID-19: a comparative, observational study

BACKGROUND Progranulin is a widely expressed pleiotropic growth factor with a central regulatory effect during the early immune response in sepsis. Progranulin signaling has not been systematically studied and compared between sepsis, community-acquired pneumonia (CAP), COVID-19 pneumonia and a sterile systemic inflammatory response (SIRS). We delineated molecular networks of progranulin signaling by next-generation sequencing (NGS), determined progranulin plasma concentrations and quantified the diagnostic performance of progranulin to differentiate between the above-mentioned disorders using the established biomarkers procalcitonin (PCT), interleukin-6 (IL-6) and C-reactive protein (CRP) for comparison. METHODS The diagnostic performance of progranulin was operationalized by calculating AUC and ROC statistics for progranulin and established biomarkers in 241 patients with sepsis, 182 patients with SIRS, 53 patients with CAP, 22 patients with COVID-19 pneumonia and 53 healthy volunteers. miRNAs and mRNAs in blood cells from sepsis patients (n = 7) were characterized by NGS and validated by RT-qPCR in an independent cohort (n = 39) to identify canonical gene networks associated with upregulated progranulin at sepsis onset. RESULTS Plasma concentrations of progranulin (ELISA) in patients with sepsis were 57.5 (42.8-84.9, Q25-Q75) ng/ml and significantly higher than in CAP (38.0, 33.5-41.0~ng/ml, p < 0.001), SIRS (29.0, 25.0-35.0~ng/ml, p < 0.001) and the healthy state (28.7, 25.5-31.7~ng/ml, p < 0.001). Patients with COVID-19 had significantly higher progranulin concentrations than patients with CAP (67.6, 56.6-96.0 vs. 38.0, 33.5-41.0~ng/ml, p < 0.001). The diagnostic performance of progranulin for the differentiation between sepsis vs. SIRS (n = 423) was comparable to that of procalcitonin. AUC was 0.90 (95% CI = 0.87-0.93) for progranulin and 0.92 (CI = 0.88-0.96, p = 0.323) for procalcitonin. Progranulin showed high discriminative power to differentiate bacterial CAP from COVID-19 (sensitivity 0.91, specificity 0.94, AUC 0.91 (CI = 0.8-1.0) and performed significantly better than PCT, IL-6 and CRP. NGS and partial RT-qPCR confirmation revealed a transcriptomic network of immune cells with upregulated progranulin and sortilin transcripts as well as toll-like-receptor 4 and tumor-protein 53, regulated by miR-16 and others. CONCLUSIONS Progranulin signaling is elevated during the early antimicrobial response in sepsis and differs significantly between sepsis, CAP, COVID-19 and SIRS. This suggests that progranulin may serve as a novel indicator for the differentiation between these disorders. TRIAL REGISTRATION Clinicaltrials.gov registration number NCT03280576 Registered November 19, 2015

Antiviral CD8(+) T Cells Restricted by Human Leukocyte Antigen Class II Exist during Natural HIV Infection and Exhibit Clonal Expansion.

CD8(+) T cell recognition of virus-infected cells is characteristically restricted by major histocompatibility complex (MHC) class I, although rare examples of MHC class II restriction have been reported in Cd4-deficient mice and a macaque SIV vaccine trial using a recombinant cytomegalovirus vector. Here, we demonstrate the presence of human leukocyte antigen (HLA) class II-restricted CD8(+) T cell responses with antiviral properties in a small subset of HIV-infected individuals. In these individuals, T cell receptor β (TCRβ) analysis revealed that class II-restricted CD8(+) T cells underwent clonal expansion and mediated killing of HIV-infected cells. In one case, these cells comprised 12% of circulating CD8(+) T cells, and TCRα analysis revealed two distinct co-expressed TCRα chains, with only one contributing to binding of the class II HLA-peptide complex. These data indicate that class II-restricted CD8(+) T cell responses can exist in a chronic human viral infection, and may contribute to immune control

Lambda and Antilambda polarization from deep inelastic muon scattering

We report results of the first measurements of Lambda and Antilambda polarization produced in deep inelastic polarized muon scattering on the nucleon. The results are consistent with an expected trend towards positive polarization with increasing x_F. The polarizations of Lambda and Antilambda appear to have opposite signs. A large negative polarization for Lambda at low positive x_F is observed and is not explained by existing models.A possible interpretation is presented.Comment: 9 pages, 2 figure