A Systematic Review of Predictor Composition, Outcomes, Risk of Bias, and Validation of COVID-19 Prognostic Scores.

BACKGROUND: Numerous prognostic scores have been published to support risk stratification for patients with coronavirus disease 2019 (COVID-19). METHODS: We performed a systematic review to identify the scores for confirmed or clinically assumed COVID-19 cases. An in-depth assessment and risk of bias (ROB) analysis (Prediction model Risk Of Bias ASsessment Tool [PROBAST]) was conducted for scores fulfilling predefined criteria ([I] area under the curve [AUC)] ≥ 0.75; [II] a separate validation cohort present; [III] training data from a multicenter setting [≥2 centers]; [IV] point-scale scoring system). RESULTS: Out of 1522 studies extracted from MEDLINE/Web of Science (20/02/2023), we identified 242 scores for COVID-19 outcome prognosis (mortality 109, severity 116, hospitalization 14, long-term sequelae 3). Most scores were developed using retrospective (75.2%) or single-center (57.1%) cohorts. Predictor analysis revealed the primary use of laboratory data and sociodemographic information in mortality and severity scores. Forty-nine scores were included in the in-depth analysis. The results indicated heterogeneous quality and predictor selection, with only five scores featuring low ROB. Among those, based on the number and heterogeneity of validation studies, only the 4C Mortality Score can be recommended for clinical application so far. CONCLUSIONS: The application and translation of most existing COVID scores appear unreliable. Guided development and predictor selection would have improved the generalizability of the scores and may enhance pandemic preparedness in the future.

Profile of the multicenter cohort of the German Cancer Consortium's Clinical Communication Platform.

Treatment concepts in oncology are becoming increasingly personalized and diverse. Successively, changes in standards of care mandate continuous monitoring of patient pathways and clinical outcomes based on large, representative real-world data. The German Cancer Consortium's (DKTK) Clinical Communication Platform (CCP) provides such opportunity. Connecting fourteen university hospital-based cancer centers, the CCP relies on a federated IT-infrastructure sourcing data from facility-based cancer registry units and biobanks. Federated analyses resulted in a cohort of 600,915 patients, out of which 232,991 were incident since 2013 and for which a comprehensive documentation is available. Next to demographic data (i.e., age at diagnosis: 2.0% 0-20 years, 8.3% 21-40 years, 30.9% 41-60 years, 50.1% 61-80 years, 8.8% 81+ years; and gender: 45.2% female, 54.7% male, 0.1% other) and diagnoses (five most frequent tumor origins: 22,523 prostate, 18,409 breast, 15,575 lung, 13,964 skin/malignant melanoma, 9005 brain), the cohort dataset contains information about therapeutic interventions and response assessments and is connected to 287,883 liquid and tissue biosamples. Focusing on diagnoses and therapy-sequences, showcase analyses of diagnosis-specific sub-cohorts (pancreas, larynx, kidney, thyroid gland) demonstrate the analytical opportunities offered by the cohort's data. Due to its data granularity and size, the cohort is a potential catalyst for translational cancer research. It provides rapid access to comprehensive patient groups and may improve the understanding of the clinical course of various (even rare) malignancies. Therefore, the cohort may serve as a decisions-making tool for clinical trial design and contributes to the evaluation of scientific findings under real-world conditions.

Dual-energy micro-CT with a dual-layer, dual-color, single-crystal scintillator.

A wide range of X-ray imaging applications demand micrometer spatial resolution. In material science and biology especially, there is a great interest in material determination and material separation methods. Here we present a new detector design that allows the recording of a low- and a high-energy radiography image simultaneously with micrometer spatial resolution. The detector system is composed of a layered scintillator stack, two CCDs and an optical system to image the scintillator responses onto the CCDs. We used the detector system with a standard laboratory microfocus X-ray tube to prove the working principle of the system and derive important design characteristics. With the recorded and registered dual-energy data set, the material separation and determination could be shown at an X-ray tube peak energy of up to 160 keV with a spatial resolution of 12 µm. The detector design shows a great potential for further development and a wide range of possible applications.

Cancer incidence and digital information seeking in Germany: a retrospective observational study.

Awareness is vital for cancer prevention. US studies show a strong link between web searches and cancer incidence. In Europe, the relationship remains unclear. This study characterizes regional and temporal relationships between cancer incidence and web searches and investigates the content of searches related to breast, cervical, colorectal, lung, prostate, and testicular cancer, brain tumors, and melanoma in Germany (July 2018-December 2019). Aggregate data from Google Ads Keyword Planner and national cancer registry data were analyzed. Spearman's correlation coefficient (rS) examined associations between cancer incidence and web search, repeated measures correlation (rrm) assessed time trends and searches were qualitatively categorized. The frequency of malignancy-related web searches correlated with cancer incidence (rS = 0.88, P = 0.007), e.g., breast cancer had more queries than the lower-incidence cervical cancer. Seasonally, incidence and searches followed similar patterns, peaking in spring and fall, except for melanoma. Correlations between entity incidence and searches (0.037 ≤ rrm ≤ 0.208) varied regionally. Keywords mainly focused on diagnosis, symptoms, and general information, with variations between entities. In Germany, web searches correlated with regional and seasonal incidence, revealing differences between North/East and South/West. These insights may help improve prevention strategies by identifying regional needs and assessing impact of awareness campaigns.

Concepts of lines of therapy in cancer treatment: findings from an expert interview-based study.

OBJECTIVE: The concept of lines of therapy (LOT) in cancer treatment is often considered for decision making in tumor boards and clinical management, but lacks a common definition across medical specialties. The complexity and heterogeneity of malignancies and treatment modalities contribute to an inconsistent understanding of LOT among physicians. This study assesses the heterogeneity of understandings of the LOT concept, its major dimensions, and criteria from the perspective of physicians of different specialties with an oncological focus in Germany. Semi-structured expert interviews with nine physicians were conducted and evaluated using qualitative content analysis. RESULTS: Most interviewees agreed that there is no single definition for LOT and found it difficult to explicate their understanding. A majority of experts stated that they had already encountered misunderstandings with colleagues regarding LOT and that they had problems with deciphering LOT from the medical records of their patients. Disagreement emerged about the roles of the following within the LOT concept: maintenance therapy, treatment intention, different therapy modalities, changing pharmaceutical agents, and therapy breaks. Respondents predominantly considered the same criteria as decisive for the definition of LOT as for a change in LOT (e.g., the occurrence of a progression event or tumor recurrence).

A precise performance-based reimbursement model for the multi-centre NAPKON cohorts - development and evaluation.

Fair allocation of funding in multi-centre clinical studies is challenging. Models commonly used in Germany - the case fees ("fixed-rate model", FRM) and up-front staffing and consumables ("up-front allocation model", UFAM) lack transparency and fail to suitably accommodate variations in centre performance. We developed a performance-based reimbursement model (PBRM) with automated calculation of conducted activities and applied it to the cohorts of the National Pandemic Cohort Network (NAPKON) within the Network of University Medicine (NUM). The study protocol activities, which were derived from data management systems, underwent validation through standardized quality checks by multiple stakeholders. The PBRM output (first funding period) was compared among centres and cohorts, and the cost-efficiency of the models was evaluated. Cases per centre varied from one to 164. The mean case reimbursement differed among the cohorts (1173.21€ [95% CI 645.68-1700.73] to 3863.43€ [95% CI 1468.89-6257.96]) and centres and mostly fell short of the expected amount. Model comparisons revealed higher cost-efficiency of the PBRM compared to FRM and UFAM, especially for low recruitment outliers. In conclusion, we have developed a reimbursement model that is transparent, accurate, and flexible. In multi-centre collaborations where heterogeneity between centres is expected, a PBRM could be used as a model to address performance discrepancies.Trial registration: https://clinicaltrials.gov/ct2/show/NCT04768998 ; https://clinicaltrials.gov/ct2/show/NCT04747366 ; https://clinicaltrials.gov/ct2/show/NCT04679584 .

Development of a headspace trap HRGC/MS method for the assessment of the relevance of certain aroma compounds on the sensorial characteristics of commercial apple juice.

A reliable and simple method was developed for the completely automatised analysis of apple juice aroma compounds. In total 26 flavour compounds could be measured by headspace trap gas chromatography/mass spectrometry (GC/MS). We used the method to analyse 85 commercially available apple juices, of which 67 apple juices were not from concentrate. Our results show that apple juices not from concentrate are mainly characterised by flavour compounds responsible for fruity, ripe, and sweet aroma impressions, such as 1-butanol, 2-methyl-1-butanol, ethylbutyrate, and ethyl-2-methylbutyrate. On the contrary, apple juices made from concentrate were dominated by acetaldehyde, E-2-hexenal, 3-methyl-1-butanol, ethyl acetate, and hexanal, which are mainly responsible for sensory impressions, such as 'green, fresh, estery'. According to our data, neither of the single compounds nor indexes calculated thereof as suggested by some authors could be used for the reliable assessment of apple juice quality. Thus, these results suggest that sensory evaluation remains the ultimate mean to reliably assess apple juice quality.

A System Identification and Implementation of a Soft Sensor for Freeform Bending.

The primary goal of this study is the formulation of a soft sensor that predicts industrially relevant mechanical properties for freeform bending. This serves as the foundation of a closed-loop property control. It is hypothesized that by inline measurement of hardness, predictions regarding residual hoop stresses, local strength and strain level can be achieved. A novel hardness-based correlation scheme is introduced, which is implemented into an extended Kalman filter (EKF) and allows an inline prediction of local strength, residual hoop stresses and plasticity. Furthermore, the ultrasonic contact impedance (UCI) method is validated as a suitable inline measuring solution.

Traumatic brain injury in a rural and an urban Tanzanian hospital--a comparative, retrospective analysis based on computed tomography.

BACKGROUND: In a resource-poor environment such as rural East Africa, expensive medical devices such as computed tomographic (CT) scanners are rare. The CT scanner at the rural Haydom Lutheran Hospital (HLH) in Tanzania therefore offers a unique chance to observe possible differences with urban medical centers in the disease pattern of trauma-related cranial pathologies. The purpose of this study was to compare traumatic brain injuries (TBIs) between a rural and an urban area of Tanzania. METHODS: HLH has 350 beds and one CT scanner. The urban Aga Khan Hospital is a private hospital with 80 beds and one CT scanner. This was a retrospective study. Data of 248 patients at HLH and of 432 patients at Aga Khan Hospital with TBI could be collected. RESULTS: The prevalence of TBI was significantly higher in the rural area compared to the urban area (34.2% vs. 21.9%, P < 0.0001). TBI due to violence was noted to occur more frequently at HLH, whereas road traffic accidents were more frequent at the Aga Khan Hospital. The number of patients showing a normal CT result was significantly higher in the urban area (53.0% vs. 35.9%, P < 0.0001). Bone fractures (35.9% vs. 15.7%, P < 0.0001) and pneumocephalus (6.9% vs. 0.9%, P < 0.0001) were diagnosed significantly more frequently in the rural survey. Soft tissue swelling (11.6% vs. 1.2%, P < 0.0001) and frontal sinus injuries (7.4% vs. 0.4%, P < 0.0001) were observed significantly more often in the urban setting. CONCLUSIONS: This study documents the burden of TBI and the differences in TBI-related CT diagnoses and their incidence between urban and rural areas in Eastern Africa. These results are important as they demonstrate that patients with severe TBI are not a primarily urban concern. Management of TBI should be included in the training curricula for health personnel alike irrespective of whether their workplace is primarily urban or rural.

Prevalence and pattern of spinal pathologies in a consecutive series of CTs/MRIs in an urban and rural Tanzanian hospital--a retrospective neuroradiological comparative analysis.

The prevalence of spinal pathologies in sub-saharan Africa has received little attention so far. The aim of the survey was to investigate and compare the prevalence pattern of spinal lesions in two different populations of Tanzania, one coming from the urban and semi-urban catchment area of Aga Khan Hospital in Dar es Salaam and the other coming from the rural catchment area of Haydom Lutheran Hospital in Mbulu, northern Tanzania. At the Aga Khan Hospital a total number of 1163 patients were included in the survey. In 50 cases (4.3%) no radiological findings were available and 150 patients (12.9%) showed no pathological abnormality. 90.4% (n = 1051) of screened population were classified in the category of extradural-extramedullary pathologies. Intradural-extramedullary lesions were observed in only three cases (0.3%). Intramedullary pathologies accounted for 2.1% (n = 24). Mean age of the screened population was 46.6 years, male-female ratio 1.08:1. At the Haydom Lutheran Hospital 105 cases were included into the study. Twenty-six patients (24.8%) showed no pathological abnormalities. Extradural-extramedullary pathologies occurred in 72.4% (n = 76) of overall cases. However, intradural-extramedullary pathologies were not seen in Haydom. Intramedullary pathologies were diagnosed in two patients (1.9%). Mean age was with 39.8 years clearly younger compared to urban areas, male-female ratio being 1.21:1, only non-significantly higher than in the Aga Khan Hospital's population. Beside this, one of the main goals of this study was to assess the frequency of infections to the spinal cord and vertebral column in rural and urban Tanzania. Surprisingly there were only few radiological findings at the Aga Khan Hospital, which suggested diagnoses consistent with tropical diseases, a striking difference from rural Haydom Lutheran Hospital, where nearly 30% of all patients showed changes on radiograph consistent with infections/infestations.

Imaging-based disease pattern in a consecutive series of cranial CTs and MRIs in a rural and an urban Tanzanian hospital: a comparative, retrospective, neuroradiological analysis.

The prevalence of neurological diseases and cranial pathologies in sub-Saharan Africa remains a very little investigated field. This study aims at providing an imaging-based overview of cranial pathologies in two Tanzanian hospitals and at identifying possible differences in the spectrum of diseases between rural and urban African populations. At rural Haydom Lutheran Hospital (Manyara region) the data of 726 patients were included in a retrospective survey. At urban Aga Khan Hospital (Dar es Salaam) the data of 1975 patients who had undergone Computed Tomography (CT) and of 537 Magnetic Resonance Imaging (MRI) patients were obtained. All three surveys showed a clear male preponderance within the populations. The median age of the patients was higher in the city (urban CT 48 years; range 0-95/MRI 39 years; 0.1-89; rural CT 32 years; 0-102). In the urban series stroke, extracranial infections, cerebral atrophy and tumours formed the main groups of diagnoses. Amongst rural patients traumatic pathologies, followed by stroke and cerebral infections/infestations were the most common diagnoses. The most striking differences were noticed with cases compatible with cerebral infections/infestations and hydrocephalus being reported more frequently in the rural population. On the other hand stroke and cerebral atrophy were more frequent amongst urban patients. In the rural catchment area the data of 51 HIV-positive CT patients could be obtained, showing a clear female preponderance. Within the urban HIV-positive subgroup of CT patients (n = 57), the gender distribution was almost equal. Furthermore, in both HIV-positive populations the proportion "compatible with cerebral infections/infestations" was higher than amongst the overall study populations. In conclusion, cranial pathologies seem to differ widely in rural and urban areas of Tanzania in particular with respect to cerebral infections and vascular disease.

The 10q25.3-26.1 G protein-coupled receptor gene GPR26 is epigenetically silenced in human gliomas.

Loss of heterozygosity (LOH) of the entire chromosome 10 is the most frequent genetic alteration in human glioblastoma (GBM). In addition to PTEN/MMAC1 on 10q23.3, clustering of partial deletion break-points on 10q25.3-26.1 points to a second suppressor locus. The proposed target gene DMBT1 was not confirmed. By somatic deletion mapping of this region, we identified the complementary DNA encoding the human homologue of rat orphan G protein-coupled receptor GPR26. GPR26 is highly expressed in fetal and adult brain, but frequently reduced or absent in glioma cells and biopsies, due to de novo methylation of its 5' CpG island. Silencing of GPR26 was reversed with 5-aza-deoxycytidine and the histone deacetylase inhibitor trichostatin A. Furthermore, overexpression of GPR26 in HEK and in U87 glioma cells increased intracellular cAMP concentration which is considered to induce astrocytic differentiation. Interestingly, we observed concomitant silencing of GPR26 with O6-methylguanine-DNA methyl transferase (MGMT), a DNA repair gene co-localized on 10q25.3-26.1 (p=0.0001). We conclude that epigenetic silencing is a common mechanism in malignant gliomas that simultaneously inactivates MGMT and GPR26. The 10q25.3-26.1 region may contain an important epigenetic pathway in brain tumorigenesis.