Trends in cancer incidence by socioeconomic deprivation in Germany in 2007 to 2018: An ecological registry-based study

Age-standardized cancer incidence has decreased over the last years for many cancer sites in developed countries. Whether these trends led to narrowing or widening socioeconomic inequalities in cancer incidence is unknown. Using cancer registry data covering 48 million inhabitants in Germany, the ecological association between age-standardized total and site specific (colorectal, lung, prostate and breast) cancer incidence in 2007 to 2018 and a deprivation index on district level (aggregated to quintiles) was investigated. Incidence in the most and least deprived districts were compared using Poisson models. Average annual percentage changes (AAPCs) and differences in AAPCs between deprivation quintiles were assessed using Joinpoint regression analyses. Age-standardized incidence decreased strongly between 2007 and 2018 for total cancer and all cancer sites (except female lung cancer), irrespective of the level of deprivation. However, differences in the magnitude of trends across deprivation quintiles resulted in increasing inequalities over time for total cancer, colorectal and lung cancer. For total cancer, the incidence rate ratio between the most and least deprived quintile increased from 1.07 (95% confidence interval: 1.01-1.12) to 1.23 (1.12-1.32) in men and from 1.07 (1.01-1.13) to 1.20 (1.14-1.26) in women. Largest inequalities were observed for lung cancer with 82% (men) and 88% (women) higher incidence in the most vs the least deprived regions in 2018. The observed increase in inequalities in cancer incidence is in alignment with trends in inequalities in risk factor prevalence and partly utilization of screening. Intervention programs targeted at socioeconomically deprived and urban regions are highly needed.     

Do they teach what they need to? An analysis of the impact of curriculum mapping on the learning objectives taught in a lecture series in surgery

Abstract

Introduction: Curriculum mapping shows concordances and differences between the intended and the taught curriculum. To our knowledge, no previous studies describe the effects that this mapping has on the curriculum. The aim of the present study is to map the content of a lecture series in surgery to the National Catalogue of Learning Objectives in Surgery and analyze the effects this mapping has on the content of the following lecture series.

Methods: All lecturers in the lecture series were directly observed by a minimum of two reviewers and learning objectives and the level of competence were documented. After the lecture series, the results were visualized within the catalog of learning objectives and were sent to the lecturers. In the following lecture series, learning objectives were documented correspondingly.

Results: In the first lecture series, 47% of the learning objectives were taught. After the mapping, the number of learning objectives that were taught increased to 59% (p?<?0.001). The increase was found in all surgical disciplines and in all levels of competences without any changes in the average duration of the lectures.

Conclusions: The presented method for mapping a curriculum effectively increased the number of taught learning objectives without requiring longer lecture durations.     

Relationship between MLH1, PMS2, MSH2 and MSH6 gene-specific alterations and tumor mutational burden in 1057 microsatellite instability-high solid tumors

Microsatellite instability-high (MSI-H) and tumor mutational burden (TMB) are predictive biomarkers for immune-checkpoint inhibitors (ICIs). Still, the relationship between the underlying cause(s) of MSI and TMB in tumors remains poorly defined. We investigated associations of TMB to mismatch repair (MMR) protein expression patterns by immunohistochemistry (IHC) and MMR mutations in a diverse sample of tumors. Hypothesized differences were identified by the protein/gene affected/mutated and the tumor histology/primary site. Overall, 1057 MSI-H tumors were identified from the 32 932 tested. MSI was examined by NGS using 7000+ target microsatellite loci. TMB was calculated using only nonsynonymous missense mutations sequenced with a 592-gene panel; a subset of MSI-H tumors also had MMR IHC performed. Analyses examined TMB by MMR protein heterodimer impacted (loss of MLH1/PMS2 vs. MSH2/MSH6 expression) and gene-specific mutations. The sample was 54.6% female; mean age was 63.5 years. Among IHC tested tumors, loss of co-expression of MLH1/PMS2 was more common (n = 544/705, 77.2%) than loss of MSH2/MSH6 (n = 81/705, 11.5%; P < .0001), and was associated with lower mean TMB (MLH1/PMS2: 25.03 mut/Mb vs MSH2/MSH6 46.83 mut/Mb; P < .0001). TMB also varied by tumor histology: colorectal cancers demonstrating MLH1/PMS2 loss had higher TMBs (33.14 mut/Mb) than endometrial cancers (20.60 mut/Mb) and other tumors (25.59 mut/Mb; P < .0001). MMR gene mutations were detected in 42.0% of tumors; among these, MSH6 mutations were most common (25.7%). MSH6 mutation patterns showed variability by tumor histology and TMB. TMB varies by underlying cause(s) of MSI and tumor histology; this heterogeneity may contribute to differences in response to ICI.     

Differential effects of bifrontal tDCS on arousal and sleep duration in insomnia patients and healthy controls

Background

Arousal and sleep represent basic domains of behavior, and alterations are of high clinical importance.

Survival of malignant mesothelioma and other rare thoracic cancers in Germany and the United States: A population-based study

Evidence on survival of malignant mesothelioma (MM) and other rare thoracic cancers is limited due to the rarity of these cancer sites. Here, we provide a comprehensive overview of MM incidence and survival after MM and other rare thoracic cancers in Germany and the United States (US). Incidence was estimated from a German National Cancer Database and from the Surveillance, Epidemiology and End Results (SEER) 18 database for 2000–2014. Patients diagnosed in 1997–2013 with malignant epithelial tumors of the trachea (Etra), epithelial tumors of the thymus (Ethy) and MM were extracted from a German cancer survival database and from the SEER 13 database. Period analysis was employed to compute 5-year relative survival (RS). During 2000–2014, an annual average of 0.9 and 0.6 MM cases per 100,000 person-years was diagnosed in Germany and the US. Rates decreased in Germany and in the US. Patients with Ethy had highest 5-year RS with US patients surviving longer (69.1% compared to 63.7%, p = 0.02). Survival after Etra was comparable in both countries (Germany 33.6%, US 34.4%, p = 0.07). Survival in MM patients was poor overall (Germany 11.8%, US 12.1%, p < 0.01). Survival improvements were only observed in MM patients in Germany (10.8% [2002–2007] vs. 13.0% [2008–2013], p < 0.01). The lack of progress in survival for Etra and Ethy patients underlines the need of novel preventive, therapeutic and diagnostic approaches. MM incidence significantly decreased in Germany and in the US. Further monitoring of MM incidence is warranted given that a peak in incidence is expected in 2020–2030 in Western countries.     

Umsetzungsstand der Telefonreanimation und Einfluss der COVID-19-Pandemie

Notfall + Rettungsmedizin -     

A novel antimetabolite: TAS-102 for metastatic colorectal cancer

TAS-102 is a new oral anti-tumor drug, composed of a thymidine-based nucleoside analog (trifluridine: FTD) and a thymidine phosphorylase inhibitor (tipiracil hydrochloride: TPI). TAS-102 has been shown to significantly improve overall survival and progression-free survival in patients with refractory metastatic colorectal cancer (mCRC) in placebo-controlled randomized phase II and III trials. The current review summarizes mechanisms of action, pharmacokinetics/dynamics and preclinical and clinical data of TAS-102 in colorectal cancer. TAS-102 is a new salvage-line treatment option for patients with mCRC. TAS-102 is well tolerated and has great potential in future clinical drug combination therapies.     

Hippocampal and medial prefrontal cortical volume is associated with overnight declarative memory consolidation independent of specific sleep oscillations

The current study was designed to further clarify the influence of brain morphology, sleep oscillatory activity and age on memory consolidation. Specifically, we hypothesized, that a smaller volume of hippocampus, parahippocampal and medial prefrontal cortex negatively impacts declarative, but not procedural, memory consolidation. Explorative analyses were conducted to demonstrate whether a decrease in slow‐wave activity negatively impacts declarative memory consolidation, and whether these factors mediate age effects on memory consolidation. Thirty‐eight healthy participants underwent an acquisition session in the evening and a retrieval session in the morning after night‐time sleep with polysomnographic monitoring. Declarative memory was assessed with the paired‐associate word list task, while procedural memory was tested using the mirror‐tracing task. All participants underwent high‐resolution magnetic resonance imaging. Participants with smaller hippocampal, parahippocampal and medial prefrontal cortex volumes displayed a reduced overnight declarative, but not procedural memory consolidation. Mediation analyses showed significant age effects on overnight declarative memory consolidation, but no significant mediation effects of brain morphology on this association. Further mediation analyses showed that the effects of age and brain morphology on overnight declarative memory consolidation were not mediated by polysomnographic variables or sleep electroencephalogram spectral power variables. Thus, the results suggest that the association between age, specific brain area volume and overnight memory consolidation is highly relevant, but does not necessarily depend on slow‐wave sleep as previously conceptualized.