Comparison of two pupillometric measures as indicators of cognitive strain and under the influence of screen luminance.

The pupil diameter has been shown to provide insight to a person's experienced cognitive strain. Pupillary light responses, however, make this measure unreliable in uncontrolled settings. Two derived indicators-Index of Cognitive Activity (ICA) and Index of Pupillary Activity (IPA)-aim to 'eliminate' lighting influences, changing based only on the perceived cognitive strain. The IPA potentially offers a valuable alternative to the ICA through its fully transparent calculation, which lifts the restrictions to proprietary software and supported eye trackers. The measures are examined and compared based on two experimental studies; (i) as indicators of cognitive strain during mental arithmetic tasks and (ii) under different conditions of computer screen luminance. Results indicate that neither indicator differentiates between the increasing levels of cognitive strain. Differences in screen luminance are reflected in both indicators, although differently between the conditions. Both results contradict the claims of the indicators and further investigations are thus required.

Work interruptions of office workers: The influence of the complexity of primary work tasks on the perception of interruptions.

BACKGROUND: Research demonstrates that work interruptions are considered one of the most common work stressors. Understanding the mechanisms of work interruptions is therefore vital to reducing worker stress and maintaining performance. OBJECTIVE: The aim of this research is to investigate the influence of the frequency of work interruptions on subjective workload in the context of office work. Specifically, the mediating influence of interruption perception as well as the moderating influence of the complexity of the primary task are examined. METHOD: The work interruptions of 492 office workers in Germany were collected by means of a one-day diary study. A mediation model and a conditional indirect effect model were calculated to examine the influence of interruption frequency on subjective workload, mediated by the individual perception of these interruptions as well as moderated by the complexity of the primary work tasks. RESULTS: The analyses indicated a significant mediation and moderation. This implies that, on the one hand, the perception of work interruptions significantly mediates the relationship between the frequency of work interruptions and subjective workload. On the other hand, more complex primary work tasks seem to strengthen the positive relationship between interruption frequency and perceived interruption overload. CONCLUSION: The study underlines that work interruptions need to be considered in a much more differentiated way than is currently the case. Both in research and in terms of intervention measures in the work context, the various influencing factors need to be identified for an assessment of the effects on the working person to be possible.

Physiological measures of operators' mental state in supervisory process control tasks: a scoping review.

Physiological measures are often used to assess the mental state of human operators in supervisory process control tasks. However, the diversity of research approaches creates a heterogeneous landscape of empirical evidence. To map existing evidence and provide guidance to researchers and practitioners, this paper systematically reviews 109 empirical studies that report relationships between peripheral nervous system measures and mental state dimensions (e.g. mental workload, mental fatigue, stress, and vigilance) of interest. Ocular and electrocardiac measures were the most prominent measures across application fields. Most studies sought to validate such measures for reliable assessments of cognitive task demands and time on task, with measures of pupil size receiving the most empirical support. In comparison, less research examined the utility of physiological measures in predicting human task performance. This approach is discussed as an opportunity to focus on operators' individual response to cognitive task demands and to advance the state of research.

Physiological measures can provide the basis for dynamic operator assistance in supervisory process control tasks. This review synthesises the existing evidence, highlighting both the aggregated empirical support and the heterogeneity of the results. To advance the status quo, a larger emphasis on physiological measures as predictors of operator performance is needed.Abbreviations: HF/E: Human factors and ergonomics; CNS: Central nervous system; PNS: Peripheral nervous system; HR: Heart rate; HRV: Heart rate variability; IBI: Interbeat interval; AVNN: Average of RR intervals; SDRR: Standard deviation of RR intervals; CVRR: Coefficient of variation in RR intervals; RMSSD: Root mean square of successive; pNNX: Percentage of successive RR intervals; MAD: Median absolute deviation; LF: Power of the low-frequency; MF: Power of the mid-frequency; HF: Power of the high-frequency; TP: Total power.

A Systematic Analysis of Incidence, Therapeutic Strategies, and In-hospital Mortality of Mallory-Weiss Syndrome in Germany.

BACKGROUND: Mallory-Weiss syndrome (MWS) is a rare cause of upper gastrointestinal bleeding from gaging or vomiting-induced mucosal lacerations at the gastroesophageal junction. Most cases do not require urgent endoscopic intervention due to the mostly self-limiting course. For more severe cases, different hemostasis techniques have been used. In small MWS cohorts, overall mortality was ~5%, but comprehensive data, as well as population-based incidence, treatment recommendations, and outcome parameters such as in-hospital mortality and adverse events, are largely lacking. METHODS: We evaluated current epidemiological trends, therapeutic strategies, and in-hospital Mortality of MWS in Germany based on standardized hospital discharge data provided by the German Federal Statistical Office from 2010 to 2019. RESULTS: A total of 59,291 MWS cases, predominately male (62%), were included into analysis. The mean number of MWS cases in Germany was 5929/year and decreased continuously during the observation period (-4.1%/y). The overall annual incidence rate (as hospitalization cases per 100,000 persons) was 7.5 with the highest incidence rate in the New Federal States (8.7). The most common comorbidities were reflux esophagitis (23.6%), diaphragmatic hernia (19.7%), and alcohol abuse (10.9%). The most frequent complication was bleeding anemia (26%), whereas hypovolemic shock (2.9%) was rare. Endoscopic injection was the most commonly performed endoscopic therapy (13.7%), followed by endoscopic clipping (12.8%), whereas the need for surgical therapy was rare (0.1%). Endoscopic combination therapies were used predominantly as a combination of injection and clipping. The overall in-hospital mortality was 2.7% and did not differ through the observation period. The presence of hypovolemic shock, acute kidney injury, sepsis, artificial ventilation, adult respiratory distress syndrome, bleeding anemia, and female sex was associated with a significantly worse prognosis. CONCLUSION: Our study gives a detailed insight into the incidence, patient-related risk factors, endoscopic treatment, and overall in-hospital mortality as well as regional differences in a large MWS collective in Germany. Furthermore, we were able to identify mortality-associated complications and their impact.

A predictive signal model for dynamic cardiac magnetic resonance imaging.

Robust dynamic cardiac magnetic resonance imaging (MRI) has been a long-standing endeavor-as real-time imaging can provide information on the temporal signatures of disease we currently cannot assess-with the past decade seeing remarkable advances in acceleration using compressed sensing (CS) and artificial intelligence (AI). However, substantial limitations to real-time imaging remain and reconstruction quality is not always guaranteed. To improve reconstruction fidelity in dynamic cardiac MRI, we propose a novel predictive signal model that uses a priori statistics to adaptively predict temporal cardiac dynamics. By using a small training set obtained from the same patient, the new signal model can achieve robust dynamic cardiac MRI in the presence of irregular cardiac rhythm. Evaluation on simulated irregular cardiac dynamics and prospectively undersampled clinical cardiac MRI data demonstrate improved reconstruction quality for two reconstruction frameworks: Kalman filter and CS. The predictive model also works with different undersampling patterns (cartesian, radial, spiral) and can serve as a versatile foundation for robust dynamic cardiac MRI.

Selective internal radiotherapy in Germany: a review of indications and hospital mortality from 2012 to 2019.

Background and Aim: Selective internal radiotherapy (SIRT) is a minimal invasive tumor therapy for hepatocellular carcinoma (HCC), biliary tract cancer (BTC), and liver metastasis of extrahepatic tumors. Comprehensive data on past and current trends of SIRT as well as outcome parameters such as in-hospital mortality and adverse events in Germany are missing. Methods: We evaluated current clinical developments and outcomes of SIRT in Germany based on standardized hospital discharge data, provided by the German Federal Statistical Office from 2012 to 2019. Results: A total of 11,014 SIRT procedures were included in the analysis. The most common indication was hepatic metastases (54.3%; HCC: 39.7%; BTC: 6%) with a trend in favor of HCC and BTC over time. Most SIRTs were performed with yttrium-90 (99.6%) but the proportion of holmium-166 SIRTs increased in recent years. There were significant differences in the mean length of hospital stay between 90Y (3.67 ± 2 days) and 166Ho (2.9 ± 1.3 days) based SIRTs. Overall in-hospital mortality was 0.14%. The mean number of SIRTs/hospital was 22.9 (SD ± 30.4). The 20 highest case volume centers performed 25.6% of all SIRTs. Conclusion: Our study gives a detailed insight into indications, patient-related factors, and the incidence of adverse events as well as the overall in-hospital mortality in a large SIRT collective in Germany. SIRT is a safe procedure with low overall in-hospital mortality and a well-definable spectrum of adverse events. We report differences in the regional distribution of performed SIRTs and changes in the indications and used radioisotopes over the years. Relevance for Patients: SIRT is a safe procedure with very low overall mortality and a well-definable spectrum of adverse events, particularly gastrointestinal. Complications are usually treatable or self-limiting. Acute liver failure is a potentially fatal but exceptionally rare complication. 166Ho has promising beneficial bio-physical characteristics and 166Ho-based SIRT should be further evaluated against 90Y-based SIRT as the current standard of care.

Dual-domain accelerated MRI reconstruction using transformers with learning-based undersampling.

Acceleration in MRI has garnered much attention from the deep-learning community in recent years, particularly for imaging large anatomical volumes such as the abdomen or moving targets such as the heart. A variety of deep learning approaches have been investigated, with most existing works using convolutional neural network (CNN)-based architectures as the reconstruction backbone, paired with fixed, rather than learned, k-space undersampling patterns. In both image domain and k-space, CNN-based architectures may not be optimal for reconstruction due to its limited ability to capture long-range dependencies. Furthermore, fixed undersampling patterns, despite ease of implementation, may not lead to optimal reconstruction. Lastly, few deep learning models to date have leveraged temporal correlation across dynamic MRI data to improve reconstruction. To address these gaps, we present a dual-domain (image and k-space), transformer-based reconstruction network, paired with learning-based undersampling that accepts temporally correlated sequences of MRI images for dynamic reconstruction. We call our model DuDReTLU-net. We train the network end-to-end against fully sampled ground truth dataset. Human cardiac CINE images undersampled at different factors (5-100) were tested. Reconstructed images were assessed both visually and quantitatively via the structural similarity index, mean squared error, and peak signal-to-noise. Experimental results show superior performance of DuDReTLU-net over state-of-the-art methods (LOUPE, k-t SLR, BM3D-MRI) in accelerated MRI reconstruction; ablation studies show that transformer-based reconstruction outperformed CNN-based reconstruction in both image domain and k-space; dual-domain reconstruction architectures outperformed single-domain reconstruction architectures regardless of reconstruction backbone (CNN or transformer); and dynamic sequence input leads to more accurate reconstructions than single frame input. We expect our results to encourage further research in the use of dual-domain architectures, transformer-based architectures, and learning-based undersampling, in the setting of accelerated MRI reconstruction. The code for this project is made freely available at https://github.com/william2343/dual-domain-mri-recon-nets (Hong et al., 2022).

Do multimodal search cues help or hinder teleoperated search and rescue missions?

In search and rescue missions, teleoperated rovers equipped with sensor technology are deployed into harsh environments to search for targets. To support the search task, unimodal/multimodal cues can be presented via visual, acoustic and/or haptic channels. However, human operators often perform the search task in parallel with the driving task, which can cause interference of attentional resources based on multiple resource theory. Navigating corners can be a particularly challenging aspect of remote driving, as described with the Cornering Law. Therefore, search cues should not interfere with cornering. The present research explores how unimodal/multimodal search cues affect cornering performance, with typical communication delays of 50 ms and 500 ms. One-hundred thirty-one participants, distributed into two delay groups, performed a target search task with unimodal/multimodal search cues. Search cues did not interfere with cornering performance with 50 ms delays. For 500 ms delays, search cues presented via the haptic channel significantly interfered with the driving task. Practitioner summary: Teleoperated rovers can support search and rescue missions. Search cues may assist the human operator, but they may also interfere with the task of driving. The study examined interference of unimodal and multimodal search cues. Haptic cues should not be implemented for systems with a delay of 500 ms or more.

The Spectrum of Co-Diagnoses in Patients with Colorectal Cancer: A Retrospective Cohort Study of 17,824 Outpatients in Germany.

Background: The prognosis of colorectal cancer (CRC) patients is determined to a decisive extent by comorbidities. On the other hand, anti-cancer treatments for CRC are associated with relevant toxicities and may therefore cause additional comorbidities. Methods: This retrospective cohort study assessed the prevalence of various diseases in patients 12 months before and 12 months after an initial diagnosis of colorectal cancer (ICD-10: C18, C20) in 1274 general practices in Germany between January 2000 and December 2018. The study is based on the Disease Analyzer database (IQVIA), which contains drug prescriptions, diagnoses, and basic medical and demographic data. Patients with and without CRC were matched by sex, age, and index year. Results: We identified several diagnoses with a significantly higher prevalence among CRC patients 12 months prior to the index date compared to controls. These diagnoses included gastrointestinal hemorrhage, hemorrhoids, perianal venous thrombosis, and abdominal and pelvic pain, as well as functional intestinal disorders. In contrast, the prevalence of lipid metabolism disorder, depression, hypertension, coronary heart disease, or acute bronchitis was significantly lower in CRC cases. After diagnosis of CRC, we found a significantly higher prevalence of anemia, polyneuropathies, functional intestinal disorders, and chronic kidney disease among CRC patients compared to the control group, while the prevalence of acute upper respiratory infections of multiple and unspecified sites and acute bronchitis was significantly lower in CRC patients compared to non-CRC patients. Conclusions: In the present study, we identified a variety of diseases occurring at higher or lower frequencies in CRC patients compared to matched controls without CRC. This might help to select patients for early CRC screening and improve the clinical management of CRC patients.

Digital platforms: Perceived criteria of success, importance of work design, occupational safety and health for present and prospective digital platforms.

BACKGROUND: Digital platforms have found their way into all our lives: they are discussed in political, economic, scientific and public fields worldwide. Platform-based work is also on the rise in the German labour market, not only in institutionalised work, but also in start-ups and spin-offs. OBJECTIVES: The article describes the results of an analysis aimed at identifying perceptions of new and already known major success factors on market entry and market penetration regarding occupational safety and health (OSH) and work design. METHODS: A total of 31 semi-standardised interviews were conducted with 39 people. First, perceived success factors in general were examined with the comparative analysis. Surprisingly, OSH/work design factors did not emerge as perceived success factors. For this reason, a in-depth analysis was performed in a secondary analysis with the structured content analysis. RESULTS: Identified perceived success factors were user orientation, scalability, network effects, niche occupation. The in-depth secondary analysis with focus on OSH/work design showed that the interviewees are aware of the topic of OSH/work design, but did not consider it to be important to economic success. CONCLUSIONS: The identified success factors may not seem surprising. What is surprising, however, is the role played by OSH/work design. Solutions must be developed that sensitize working persons in the platform sector to the topic of OSH/work design. A two-step process may be useful: First, uniform regulations and laws must be anchored in the platform architecture. Second, various measures and training courses can be designed to inform and raise awareness.

Diagnosis clarification by generalization to patient-friendly terms and definitions: Validation study.

BACKGROUND: Now that patients increasingly get access to their healthcare records, its contents require clarification. The use of patient-friendly terms and definitions can help patients and their significant others understand their medical data. However, it is costly to make patient-friendly descriptions for the myriad of terms used in the medical domain. Furthermore, a description in more general terms, leaving out some of the details, might already be sufficient for a layperson. We developed an algorithm that employs the SNOMED CT hierarchy to generalize diagnoses to a limited set of concepts with patient-friendly terms for this purpose. However, generalization essentially implies loss of detail and might result in errors, hence these generalizations remain to be validated by clinicians. We aim to assess the medical validity of diagnosis clarification by generalization to concepts with patient-friendly terms and definitions in SNOMED CT. Furthermore, we aim to identify the characteristics that render clarifications invalid. RESULTS: Two raters identified errors in 12.7% (95% confidence interval - CI: 10.7-14.6%) of a random sample of 1,131 clarifications and they considered 14.3% (CI: 12.3-16.4%) of clarifications to be unacceptable to show to a patient. The intraclass correlation coefficient of the interrater reliability was 0.34 for correctness and 0.43 for acceptability. Errors were mostly related to the patient-friendly terms and definitions used in the clarifications themselves, but also to terminology mappings, terminology modelling, and the clarification algorithm. Clarifications considered to be most unacceptable were those that provide wrong information and might cause unnecessary worry. CONCLUSIONS: We have identified problems in generalizing diagnoses to concepts with patient-friendly terms. Diagnosis generalization can be used to create a large amount of correct and acceptable clarifications, reusing patient-friendly terms and definitions across many medical concepts. However, the correctness and acceptability have a strong dependency on terminology mappings and modelling quality, as well as the quality of the terms and definitions themselves. Therefore, validation and quality improvement are required to prevent incorrect and unacceptable clarifications, before using the generalizations in practice.

Using IoT devices for sensor-based monitoring of employees' mental workload: Investigating managers' expectations and concerns.

Although the objective assessment of mental workload has been a focus of human factors research, few studies have investigated stakeholders' attitudes towards its implementation in real workplaces. The present study addresses this research gap by surveying N = 702 managers in three European countries (Germany, United Kingdom, Spain) about their expectations and concerns regarding sensor-based monitoring of employee mental workload. The data confirm the relevance of expectations regarding improvements of workplace design and employee well-being, as well as concerns about restrictions of employees' privacy and sovereignty, for the implementation of workload monitoring. Furthermore, Bayesian regression models show that the examined expectations have a substantial positive association with managers' willingness to support workload monitoring in their company. Privacy concerns are identified as a significant barrier to the acceptance of workload monitoring, both in terms of their prevalence among managers and their strong negative relationship with monitoring support.

Why cumulative loading calculated using non-weighted integration may not be suitable for assessing physical stress of the lower back: an empirical investigation of strain during lifting and lowering tasks.

When work-related physical stress is assessed using non-weighted integration, it is assumed that different loading conditions have a sufficiently comparable effect on the human body as long as the area under the loading curve is the same. Growing evidence cast doubt on whether this simple calculation can adequately estimate physical work-related strain. This study investigates in vivo, focussing on the lower back, whether the non-weighted method adequately reflects work-related physical strain of the lower back. Strain data resulting from lifting/lowering tasks performed in a laboratory study with an identical area under the loading curve but different load intensities were compared. Results showed that the non-weighted method does not sufficiently reflect the resulting muscular, cardiovascular and perceived strain but underestimates the influence of higher load intensity even in the range of medium physical exposure. Further research is needed regarding the determination of weighting factors and limit values. Practitioner Summary Given the dynamic nature of most physical work activities, the assessment of time-varying loading of the lower back is of particular interest in practice. Results show that the widely used non-weighted calculation method does not accurately reflect the resulting physical strain but underestimates the influence of higher load intensity.Abbreviations: MSD: musculoskeletal disorders; WMSD: work-related musculoskeletal disorders; KIM-LHC: Key Indicator Method Lifting, Holding, Carrying; RES: right erector spinae longissimus; LES: left erector spinae longissimus; HR: heart rate; RPE: rating of perceived exertion; EMG: surface electromyography; ECG: electrocardiography; SENIAM: Surface ElectroMyoGraphy for the Non-Invasive Assessment of Muscles; MVC: maximum voluntary contraction; ANOVA: analysis of variance; Std. error: standard error HIGHLIGHTSResults of this empirical investigation suggest that the widely used non-weighted calculation method is not fully suitable for calculating cumulative loading of the lower back.Even in the range of medium physical exposure the non-weighted calculation method does not accurately reflect the resulting strain on the human body but tends to underestimate the influence of higher load intensity due to higher external weight.Despite the same cumulative loading value obtained when using the non-weighted method, the resulting physical strain values are generally about 20-25% higher.The results may be used to further develop ergonomic assessment methods in order to avoid a misclassification of loading conditions and to prevent the risk of overexertion.

Gastrectomy Versus Esophagectomy for Gastroesophageal Junction Tumors: Short- and Long-Term Outcomes From the Dutch Upper Gastrointestinal Cancer Audit.

OBJECTIVE: Investigate long-term survival, morbidity, mortality, and pathology results in patients following esophagectomy or total gastrectomy for gastroesophageal junction (GEJ) cancer. BACKGROUND: Both a total gastrectomy and an esophagectomy may be valid treatment options in patients with GEJ cancer. Which procedure results in the most optimal patient outcome is not well studied. The aim of this study was to investigate the long-term survival, morbidity, mortality, and pathology results in patients following esophagectomy or total gastrectomy for GEJ cancer. METHODS: A retrospective comparative cohort study of prospectively collected data from the Dutch Upper GI Cancer Audit combined with survival data of the Dutch medical insurance database was performed. Patients with GEJ cancer in whom a total gastrectomy or an esophagectomy was performed between 2011 and 2016 were compared. The primary outcome was 3-year overall survival. Postoperative morbidity, mortality, 3-year conditional survival, radicality of resection, and lymph node yield were secondary endpoints. RESULTS: A total of 871 patients were included: 790 following esophagectomy and 81 following gastrectomy. The 3-year overall survival was 35.8% after esophagectomy and 28.4% after gastrectomy (hazard ratio 1.2, 95% confidence interval 0.721-1.836, P = 0.557). Postoperative morbidity, mortality, radicality of resection, lymph node yield, and 3-year conditional survival did not differ significantly between groups. CONCLUSION: A total gastrectomy and an esophagectomy for GEJ cancer show largely comparable results with regard to long-term survival, postoperative morbidity, mortality, and pathology results. If both procedures are feasible, other parameters such as surgeon's experience and quality of life should be considered when planning for surgery.

Accuracy of a markerless motion capture system for postural ergonomic risk assessment in occupational practice.

Established methods for postural ergonomic risk assessment in occupational practice are mostly time-consuming and need to be conducted by experts. Use of technology could improve postural ergonomic risk assessments with regard to time efficiency and accuracy. A study was conducted to assess the accuracy of a markerless motion capture system (Microsoft Kinect V2) compared to a marker-based motion capture system (Vicon Bonita). Angles of different body segments were analysed. The results show major inaccuracies of the markerless motion capture system for capturing axial trunk rotation (mean angular deviation of 14.04°) indicating that potential health risks could be underestimated. Combined working postures of axial trunk rotation and arm anteversion show issues with self-occlusion. Based on the findings, it is discussed whether the detected inaccuracies for axial trunk rotation are likely to lead to overestimation or underestimation of potential health risks when conducting an ergonomic risk assessment.

Treating Early Delayed Gastric Tube Emptying after Esophagectomy with Pneumatic Pyloric Dilation.

INTRODUCTION: Endoscopic pneumatic pyloric balloon dilation is a treatment option for early postoperative delayed gastric tube emptying following esophageal resection. This study aimed to determine the safety and effectiveness of endoscopic balloon dilation. METHODS: Between 2015 and 2018, patients with delayed gastric emptying 8-10 days after esophageal resection with gastric tube reconstruction due to esophageal carcinoma were considered for inclusion. Inclusion criteria were ≥1 of the following: nasogastric tube production ≥500 mL/24 h, ≥300 mL gastric retention, ≥50% gastric tube dilatation on X-ray, or nasogastric tube replacement. Patients were excluded on evidence of anastomotic leakage or reintervention. Success was defined as the ability to expand intake without needing to replace the nasogastric tube. Dilation was performed using a 30-mm Rigiflex balloon. RESULTS: Fifteen patients underwent pyloric dilation, 12 according to the study protocol. Treatment was performed at a median of 12 days (IQR 9-15) postoperatively. Success was achieved in 58%. At 3 months, 8 patients progressed to exclusively oral intake. The remaining 4 patients had supplementary nightly enteral tube feeding. There were no adverse events. CONCLUSION: Endoscopic balloon dilation of the pylorus is a safe, feasible therapy for early postoperative delayed gastric emptying. With a success rate of 58%, a clinical trial is a necessary next step.

A meta-analytic review of the reliability of the Index of Cognitive Activity concerning task-evoked cognitive workload and light influences.

The Index of Cognitive Activity (ICA) was introduced as a promising pupillary workload measure for field investigations since, unlike pupil dilation, it is not affected by illumination. Recent studies have investigated the ICA for task-evoked cognitive workload with contradictory findings. However, few studies investigated the influence of illumination on the ICA. Therefore, to examine inconsistencies regarding the reliability for workload measurement and the effects of light, a meta-analysis was conducted based on a structured literature review. The meta-analysis considered k = 14 studies with a total sample size of N = 751 participants. Results showed significant effects for workload (r = 0.61) and light (r = 0.45) on the ICA. Since moderating effects were found for several between-study differences, it seems likely that different cognitive processes and settings affect the indicator and should be considered in empirical investigations. According to the findings, the ICA is a reliable indicator for task-evoked workload. However, light influences were found which indicates that evidence-based conclusions regarding the ICA's practical applicability require further research.

Serum Levels of Soluble Urokinase Plasminogen Activator Receptor Predict Tumor Response and Outcome to Immune Checkpoint Inhibitor Therapy.

BACKGROUND: Immune checkpoint inhibitors (ICIs) have led to a paradigm shift in cancer therapy, improving outcomes in the treatment of various malignancies. However, not all patients benefit to the same extend from ICI. Reliable tools to predict treatment response and outcome are missing. Soluble urokinase plasminogen activator receptor (suPAR) is a marker of immune activation, whose levels are prognostic in various cancers. We evaluated circulating suPAR levels as a novel predictive and prognostic biomarker in patients receiving ICI therapy for solid tumors. METHODS: A total of n = 87 patients receiving ICI therapy for different solid malignancies as well as 32 healthy controls were included into this study. Serum levels of suPAR were measured by ELISA prior to and sequentially at two time points during ICI therapy. RESULTS: Baseline suPAR serum levels were significantly higher in solid tumor patients compared to healthy controls. Importantly, patients with low suPAR levels both before or during ICI treatment were more likely to have a favorable response to treatment at three and six months, respectively. This finding was confirmed by multivariate binary logistic regression analysis including several clinicopathological parameters. Moreover, circulating suPAR levels before and during therapy were an independent prognostic factor for overall survival (OS). As such, patients with initial suPAR levels above our ideal prognostic cut-off value (4.86 ng/ml) had a median OS of only 160 days compared to 705 days for patients with suPAR levels below this cut-off value. Finally, low baseline suPAR levels identified a subgroup of patients who experienced ICI-related side effects which in turn were associated with favorable treatment response and outcome. CONCLUSION: Our data suggest that measurements of suPAR serum levels are a previously unknown, easily accessible tool to predict individual treatment response and outcome to ICI therapy. Circulating suPAR might therefore be implemented into stratification algorithms to identify the ideal candidates for ICI treatment.

Sensitivity of anti-SARS-CoV-2 serological assays in a high-prevalence setting.

Evaluation and power of seroprevalence studies depend on the performed serological assays. The aim of this study was to assess four commercial serological tests from EUROIMMUN, DiaSorin, Abbott, and Roche as well as an in-house immunofluorescence and neutralization test for their capability to identify SARS-CoV-2 seropositive individuals in a high-prevalence setting. Therefore, 42 social and working contacts of a German super-spreader were tested. Consistent with a high-prevalence setting, 26 of 42 were SARS-CoV-2 seropositive by neutralization test (NT), and immunofluorescence test (IFT) confirmed 23 of these 26 positive test results (NT 61.9% and IFT 54.8% seroprevalence). Four commercial assays detected anti-SARS-CoV-2 antibodies in 33.3-40.5% individuals. Besides an overall discrepancy between the NT and the commercial assays regarding their sensitivity, this study revealed that commercial SARS-CoV-2 spike-based assays are better to predict the neutralization titer than nucleoprotein-based assays are.