Sites In Germany Research Articles

Sex-disaggregated analysis of central venous catheter-related bloodstream infections in patients with cancer

Introduction: Men are generally more susceptible to bacterial infections than women. Central venous catheters (CVCs), often used to administer systemic treatment in patients with cancer, are an important source of infection. However, little is known about sex-specific differences of CVC-related bloodstream infections (CRBSIs) in patients with cancer. This study aimed to compare CRBSIs in men vs. women in a large cohort of patients with cancer. Methods: Data were derived from the SECRECY registry including non-selected patients with centrally inserted non-tunneled internal jugular or subclavian vein CVCs in 10 hematology and oncology sites in Germany. Only CRBSIs classified as definite CRBSI (dCRBSI) or probable CRBSI were included, and the combination of both was summarized as dpCRBSI. CVCs were matched 1:1 for underlying disease, anatomic site of CVC insertion, type of CVC dressing, antimicrobial coated CVC, complicated CVC insertion and CVC in situ time by propensity score matching (PSM). Endpoints were CRBSI rates and incidences in CVCs inserted in men vs. women. Results: A total of 5075 CVCs registered from March 2013 to March 2024 were included in the analysis, of which 3024 comprises the PSM cohort. 1512 (50.0%) CVCs were inserted in men. Underlying diseases mainly were hematological malignancies (96.4%). While there was no statistically significant difference between men and women in the dCRBSI rate (5.4% vs. 4.1%; p=0.12) and the dCRBSI incidence (3.8 vs. 2.9/1000 CVC days; p=0.11), the rate of dpCRBSI (9.9% vs. 6.7%; p=0.002) and the dpCRBSI incidence (7.0 vs. 4.7/1000 CVC days; p=0.002) were significantly higher in men vs. women. The proportion of coagulase-negative staphylococci as causative agent of both dCRBSI and dpCRBSI was higher in men than in women (58.8% vs. 41.2%; p=0.07, and 61.5% vs. 38.5%; p=0.002, respectively). A multivariable regression revealed neutropenia as an independent risk factor for dCRBSI and male sex as risk factor for dCRBSI and dpCRBSI. Conclusion: In patients with hematological malignancies, men have a higher risk of CRBSI than women. This finding may be attributed to the high number of jugular vein inserted CVCs which in men may be associated with higher rates of skin colonization than in women. Special preventive measures such as earlier removal of CVCs in men may be studied in future.

Short‐course subcutaneous treatment with birch pollen allergoids greatly improves symptom and medication scores in birch allergy

AbstractBackgroundSubcutaneous immunotherapy has emerged as an effective option for treating allergic diseases. Here, we assessed the clinical impact of the mannan‐conjugated birch pollen polymerized allergoid T502 in birch pollen‐induced allergic rhinoconjunctivitis.MethodsIn this prospective, randomized, double‐blind placebo‐controlled phase III trial, 298 birch pollen–allergic adult patients were treated across 28 trial sites in Germany. Patients received either placebo or 23,000 mTU T502 subcutaneously over five pre‐seasonal visits. Efficacy was assessed by comparing the combined symptom and medication score (CSMS) between placebo and T502 during the peak birch pollen season 2022. Safety, tolerability and immunologic effects were also analyzed.ResultsDuring the peak birch pollen season, the median CSMS of the T502 group was reduced by 33% (p = 0.002) compared to placebo. The median daily symptom score and daily medication score were reduced by 30.4% (p < 0.001) and 56.3% (p = 0.045), respectively. Health related quality of life improved as reflected by reduction of RQLQ values by 31.5% (p < 0.0001). Production of Bet v 1 sIgG4 and Bet v 1 sIgG increased up to 6.2‐fold and 3‐fold respectively in the T502 group (p < 0.0001). The sIgE/sIgG4 ratio was strongly reduced in the T502 group at V7 (−62.9%, p < 0.0001).No fatalities nor serious adverse events were reported. In total, 16 systemic allergic reactions occurred (Grade I/II).ConclusionsTreatment with T502 significantly reduced symptoms and medication need in rhinoconjunctivitis patients. The treatment is well tolerated and safe.

The association between traffic noise and self-rated health within the German National Cohort (NAKO)

Abstract Objectives Traffic noise can cause stress and disturb sleep, impacting health in many ways. However, few large studies on this topic exist. We investigated the association between traffic noise and self-rated health (SRH) within the German National Cohort (NAKO). Methods NAKO enrolled >200,000 adults ages 20-74 at 18 sites in Germany. We used logistic regression to test whether 1) annual mean 24-hour ambient traffic noise levels at or above 55 dB(A) within a 10-meter residential buffer and 2) subjectively reported nighttime traffic noise annoyance were associated with higher odds of reporting fair/poor SRH. We calculated these associations within the full sample, stratified by sex, and stratified by age group (≤39 years, 40-59 years, ≥60 years). We adjusted for study site, age, sex, marital status, education level, and migration background. Results Among participants without missing data (n = 121,232), moderate annoyance was associated with 1.27 higher odds (95% CI 1.21-1.32) and strong annoyance with 1.75 higher odds (95% CI 1.65-1.84) of fair/poor SRH, while annual mean noise ≥55 dB(A) was associated with 1.07 higher odds (95% CI 1.03-1.12). Females who reported strong annoyance had especially high odds of fair/poor SRH (OR 1.81, 95% CI 1.69-1.95), as did those aged 40-59 years who reported high annoyance (OR 1.78, 95% CI 1.66-1.92). Those 39 and under had no significant increase in odds of fair/poor SRH if they reported moderate annoyance or if they were exposed to ≥ 55 dB(A) annual mean noise. In single exposure models, noise annoyance and objectively measured noise were both significantly associated with higher odds of reporting fair/poor SRH, but in combined models, the effect of objectively measured noise became insignificant while the effect of annoyance remained strongly significant. Conclusions These findings confirm that traffic noise is an important public health issue. Further analyses on most affected populations should inform noise protection policies. Key messages • Higher levels of traffic noise are associated with worse self-rated health. • Ambient noise is an important public health issue for which more research is needed.

Non-target screening reveals 124 PFAS at an AFFF-impacted field site in Germany specified by novel systematic terminology.

The uncontrolled release of aqueous film-forming foam (AFFF) ingredients during a major fire incident in Reilingen, Germany, in 2008 led to significant soil and groundwater contamination. As the identity of fluorochemical surfactants in AFFF are often veiled due to company secrets, it is important to characterize AFFF contaminations and their impact on the environment comprehensively. In this study, we adapted a systematic approach combining a suitable extraction method with liquid chromatography high-resolution quadrupole time-of-flight mass spectrometry (LC-QTOF-MS) for an extensive non-targeted analysis. Our analysis identified 124 per- and polyfluoroalkyl substances (PFAS) from 42 subclasses in the contaminated soil (confidence levels of identification between 1 and 3). Typical for AFFF-impacted field sites, these included anionic, cationic, and zwitterionic substances with perfluoroalkyl chains spanning from 3 to 14 carbon atoms. Furthermore, we identified 1 previously unreported substance, and detected 9 PFAS subclasses for the first time in soil. AFFFs have long been employed to extinguish large hydrocarbon fires, yet their environmental consequences remain a concern. This study sheds light on the complex composition of AFFFs at this particularly contaminated area, emphasizing the necessity for extensive contaminant characterization as sound basis for informed management strategies to mitigate their adverse effects. AFFF PFAS are often named differently in the literature, leading to inconsistency in terminology. To address this issue, we introduced partially new terminology for AFFF-related PFAS to establish consistent terminology, to facilitate communication of identified compounds, and to ensure that the chemical structure can be directly derived from acronyms.

Cerebral vasculitis as clinical manifestation of neuroborreliosis: Pattern of vascular pathology and prognostic factors of outcome.

Neuroborreliosis is a tick-borne condition that affects the central and/or peripheral nervous system. Cerebral infarction associated with neuroborreliosis-related vasculitis has been reported in only a handful of cases. Therefore, specific patterns of vascular pathology and prognostic outcome factors are still incompletely understood. To determine the pattern of vascular pathology and prognostic outcome factors in patients with neuroborreliosis-related vasculitis. We performed a longitudinal multicenter study between 1997 and 2022 in five academic study sites in Germany with a cumulative reference area of 1,620,000 inhabitants. All patients diagnosed with neuroborreliosis-associated cerebral vasculitis were included. The evaluation of clinical parameters, including NIH Stroke Scale (NIHSS), disability ranking (modified Rankin Scale, mRS), and neuroimaging, was performed at admission as well as after 3 and 12 months. Linear regression analysis was used to identify the independent predictors of recurrent strokes, involvement of posterior circulation, or multiple vessels. Patients with neuroborreliosis-related vasculitis (n = 51) were relatively young (mean age: 62 years) and displayed a predominance of vascular events within the posterior circulation (60.8%). A history of smoking was linked to recurrent strokes/TIA (64.7% vs. 23.5%; p = 0.006), strokes in multiple territories (100% vs. 35.9%; p < 0.0001), and posterior circulation events (64.5% vs. 30.0%, p = 0.017), whereas other cardiovascular risk factors showed no significant differences. Linear regression analysis corroborated smoking's association with recurrent strokes/ transient ischemic attacks (B: 0.412; p = 0.002), multiple territory strokes/TIA (B: 0.467; p = 0.033), and posterior circulation events (B: 0.317; p = 0.033). A thorough CSF examination for neuroborreliosis is crucial, especially in younger stroke patients, particularly those experiencing posterior circulation ischemic events. Smoking cessation should be prompted in patients with neuroborreliosis-associated cerebral vasculitis.

Navigating transitions: a qualitative study of nursing teams' experiences of educational and cultural transitions in Germany.

The global migration of health professionals in general and nurses in particular, has led to nursing shortages and socioeconomic impacts on health systems in both source and destination countries. Adding to the complexity of the situation is the fact that the nursing profession itself is evolving from a vocational to an academic one. Although nursing migration and academization have been studied from either an institutional or an individual perspective, there is a gap in the literature regarding how nursing teams experience these transitions. This study aims to explore how nursing teams navigate through the transitions of academization and internationalization of the current dynamic nursing landscape in Germany. Based on social constructivism epistemology this qualitative study involved face-to-face focus group discussions conducted at several hospital sites in Germany from September 2021 to May 2023. The focus group discussions were audio-recorded, transcribed, and analysed using content analysis; the four dimensions of transition theory according to Schlossberg's Four S (4S) framework (self, situation, support, and strategy) were used as a priori items to construct the coding framework. Nine focus group discussions were conducted with a total of 40 nurses from different educational and migrant backgrounds. The analysis showed that the transition experiences of the nursing teams were heterogeneous, with educational and national backgrounds playing an important role in how realistic their expectations of their professional roles and identities were. The dynamic situation characterized by a shortage of qualified nursing staff, increases the pressure on nursing teams and underscores the importance of employer-provided and peer support. Onboarding and communication are key strategies used depending on the duration of the employee turnover. This study provides insights into the challenges and coping strategies of nursing teams in the current dynamic scene of migration, academicization and professional socialisation in Germany. Extending the Schlossberg 4S framework from the individual to the team perspective provides a comprehensive view of the transitional experiences of nursing teams. Within each domain of the framework, the experiences of nursing teams are remarkably diverse. Educational background (vocational or academic) and origin (German or foreign trained) play an important role in shaping the transitional experiences of nursing teams.

Site conditions rather than provenance drive tree growth, climate sensitivity and drought responses in European beech in Germany

Ongoing climate change and associated extreme events strongly impact the growth and vitality of forest ecosystems in Europe. Because of its’ high drought sensitivity, European beech, which is considered as climax tree species in large parts of Central Europe, may specifically suffer. Hence, recent studies increasingly focus on the resistance and resilience of beech growth to climate change. Intra-specific variations in growth responses by comparing different beech provenances, however, received less attention, as did the question whether provenance selection can be used to mitigate potential future negative impacts of climate change. Therefore, we here investigated 24 provenances belonging to the International Beech Provenance Trial growing at three sites in Germany along a latitudinal gradient (study sites are referred to as ’North’, ‘Center’, ‘South’). Specifically, we compared tree-ring width (TRW), diameter breast height (DBH), climate-growth relationships, as well as drought resistance and resilience in the extreme years 2003 and 2018. Large differences in growth performance were observed between the three study sites. At site North, beech trees showed the highest DBH and TRW. Tree growth was predominantly driven by previous-year October and current-year winter temperature, whereas growth at sites Center and South was significantly impacted by summer SPEI and constrained by precipitation in late winter and early June, respectively. Overall, drought responses in 2003 were less variable than in 2018. We found increasing resistance and decreasing resilience from the wetter North to the drier South, but with minimal differences between the Center and the South. Whereas differences between study sites were large, provenance differentiation within sites was comparably low, substantiating that beech is a highly plastic tree species. Even though some provenances were found to perform slightly better or worse, differences were not statistically significant and show unclear patterns. Hence, we conclude that climate change will affect beech forests in Europe mainly depending upon site conditions, and that provenance selection may not ensure superior growth performance.

Assessment of process water quality (depending on the presence of process water systems) in car wash facilities across Germany and the Netherlands

ABSTRACT There are around 2,500 car wash lines in Germany, consuming around 30 million m3 of drinking water per year. In view of the increasing scarcity of water, this level of consumption could soon be restricted by law, as it is in some countries. There are only a few systematic studies on process water systems in car wash lines in Middle Europe; we therefore carried out a survey to determine process water quality parameters (COD, turbidity, water hardness, pH, conductivity, dissolved O2, and temperature). Data were collected and analysed from 63 different locations in Germany and the Netherlands. In addition, longitudinal parameters were measured for 1 year at a single state-of-the-art site in Germany. The scatter of the observed values was quite considerable. The average COD in water of car wash sites with biological treatment was found to be significantly lower than in car wash sites working with filter treatment. Overall, the deviation of the pollution parameters was higher than expected. Surprisingly, there is hardly any reliable data on freshwater consumption in the car wash facilities. As most of the long-established facilities do not have a modern water treatment system, freshwater consumption is up to 300 L per car washed.

Taxon‐specific response of natural enemies to different flower strip mixtures

Abstract Flower strips are a prominent agri‐environmental scheme with the central objective to promote biodiversity and maintain associated ecosystem services. The promotion of natural enemies by increasing resource availability through flower strips is a promising approach for integrated pest management. In a 3‐year field study, two annual and two perennial flower strip mixtures, as well as a grass mixture, were tested regarding their attractiveness for natural enemies at three different study sites in Germany. Natural enemies were sampled annually in nine sampling rounds at a 10‐day rhythm using sweep netting and pitfall traps. To assess available floral resources, we estimated the species‐specific flower cover and classified species into flower types. Flower strip mixtures differed in their attractiveness to natural enemies. Treatment effects on arthropod activity density were most pronounced in the second and third year. Overall, perennial were more attractive than annual flower strip mixtures for most natural enemies, however, the response to flower strip mixtures varied significantly among taxa. For example, perennial flower strips showed a two‐ to fourfold increase of plant‐dwelling spider and parasitoid wasp activity density as well as higher numbers of juvenile stages of predatory bugs and rove beetles compared to annual flower strips. In contrast, annual flower strip mixtures showed the highest attractiveness for ground beetles. Moreover, different natural enemy taxa were associated with varying flower strip characteristics such as flower type proportion, herbivore availability and plant species richness. Synthesis and applications. We found taxon‐specific responses of natural enemies to different flower strips, which provide guidance for the floral composition of flower strips in order to maximize their effectiveness for natural pest control. We suggest the use of perennial mixtures with high proportion of flower heads (Asteraceae) and disk flowers (esp. Apiaceae, Rubiaceae, Brassicaceae) in particular, but also flag blossoms (Fabaceae) as these flower types were positively associated with several natural enemy groups. However, since we found mixed responses to flower types, specific flower strip composition will ultimately depends on its objective.

Site characteristics determine the prevalence of extreme weather events affecting freshwater macroinvertebrate communities

Understanding the impacts of extreme weather events on freshwater ecosystems is imperative during a time when a multitude of challenges compromises these environments' health. Exploring how such events affect macroinvertebrate communities in rivers sheds light on the resilience of freshwater ecosystems, which is essential for human well-being and biodiversity conservation. In this study, long-term time series of benthic macroinvertebrate communities from four sites along three freshwater streams within the Rhine-Main-Observatory Long-Term Ecological Research site in Germany were analyzed. Each of them was sampled annually over a span of ~20 years to assess the impacts of extreme weather events (floods, droughts, and extreme heat) on macroinvertebrate communities. The findings reveal that the effects of extreme events are site-specific, suggesting that the impacts of an extreme event can vary based on several potential factors, including the life history traits of the organisms within the community and, among others, the hydrography of the site. Moreover, the analysis highlights that the cumulative impact of these events over time is more significant than the impact of a single event's magnitude, while following distinct temporal dynamics. This underscores the importance of considering both the temporal dynamics and the biological characteristics of communities when evaluating the consequences of extreme weather events on biodiversity, illustrating that the resilience of freshwater ecosystems and their biodiversity under such conditions depends on a complex interplay of factors rather than the severity of individual events.

Synchronised monitoring of plant and insect diversity: a case study using automated Malaise traps and DNA-based methods.

The occurrence and distribution of insects and their possible associations with plant species are largely unknown in Germany and baseline data to monitor future trends are urgently needed. Using newly-designed automated Malaise trap multi-samplers, the occurrence of insect species and their potential associations with plants was monitored synchronously at two contrasting field sites in Germany: an urban botanical garden and a forest research station. Taxa were identified by metabarcoding of the insects and the plant traces present in the preservative ethanol of the Malaise trap samples. For comparison, a botanical survey was conducted in the vicinity of the traps. Across both sites, we identified a total of 1290 exact sequence variants (ESVs) assigned to Insecta, of which 205 are known to be pollinators. In the botanical garden, we detected the occurrence of 128 plant taxa, of which 41 also had one of their known insect pollinator species detected. Insect species richness was highest in May, mainly attributed to an increase in Diptera. These results present a case study of the applicability of automated sampling and DNA-based methods to monitor the timings of flowering and corresponding activity of plant-visiting insects.

Oral anticoagulation with Edoxaban for stroke prevention in patients with atrial fibrillation: Analysis of 1-year follow-up data of routine clinical practice in Germany, Austria and Switzerland (DACH) from the ETNA-AF registry

Non-vitamin-K oral anticoagulants (NOACs) are safe and effective for stroke prevention in patients with atrial fibrillation (AF). Data on the safety and efficacy of Edoxaban in routine care in Germany, Austria and Switzerland (DACH) are limited. We report one-year outcomes in patients with AF treated with Edoxaban in routine care. The ETNA-AF-Europe study (Clinicaltrials.gov:NCT02 944 019) is a multicenter, prospective, observational study that enrolled 13 092 patients with AF treated with Edoxaban from 852 sites across 10 European countries (Austria, Belgium, Germany, Ireland, Italy, the Netherlands, Portugal, Spain, Switzerland, and the United Kingdom). The DACH-cohort consists of 5457 (41,7 %) patients of sites in Germany, Austria and Switzerland. Patients had a mean age of 74 years (2384 [44 %]women) and a mean CHA2DS2-VASc-score of 3.2 ± 1.4. A label-conform dosing of Edoxaban was administered to 4309 patients (78,9 %). At the one-year-follow-up a stroke or systemic embolism occurred in 42 patients (0,8 %/year), and severe bleeding was reported in 36 patients (0,7 %/year). Ten patients (0,2 %/year) suffered intracranial and 13 patients (0,3 %/year)gastrointestinal bleeding. Numbers of death from all causes and cardiovascular death occurred in 179 patients (3,4 %/year) and 85 patients (1,6 %/year), respectively. Age > 75 years, frailty and a CHA2DS2-VASc score ≥ 4 were associated with a higher all-cause mortality - and those patients were more likely to suffer a stroke or a major bleeding event. In Germany, Austria and Switzerland in patients with AF on Edoxaban therapy for stroke prevention the number of stroke and major bleeding events is low. Increasing morbidity is associated with a higher number of important clinical events.

Final Analysis of a Noninterventional Study on Cabozantinib in Patients With Advanced Renal Cell Carcinoma After Prior Checkpoint Inhibitor Therapy of the German Interdisciplinary Working Group on Renal Tumors (IAG-N)

BackgroundEfficacy of treatment after failure of check point inhibitors (ICI) therapy remains ill-defined in metastatic renal cell carcinoma (mRCC). ObjectiveTo evaluate the safety and effectiveness of cabozantinib after failure of ICI-based therapies. Design, setting and participantsPatients with mRCC who concluded cabozantinib treatment directly after an ICI-based therapy were eligible. Data was collected retrospectively from participating sites in Germany. InterventionsCabozantinib was administered as a standard of care. Outcome measurements and statistical analysisAdverse events (AE) were reported according to CTCAE v5.0. Objective response rate according to RECIST 1.1 and Progression Free Survival (PFS) were collected from medical records. Descriptive statistics and Kaplan-Meyer-plots were utilized. Results and limitationsAbout 56 eligible patients (71.4% male) with median age of 66 years and clear cell histology in 66.1% (n = 37) were analyzed. 87.5% (n = 49) had ≥ 2 previous lines. IMDC risk was intermediate or poor in 17 patients (30.4%) and missing in 66.1%. 20 patients (35.7%) started with 60 mg. 55.4% (n = 31) required dose reductions, 26.8% (n = 15) treatment delays and 1.8% (n = 1) treatment discontinuation. Partial response was reported in 10.7% (n = 6), stable and progressive disease were reported in 19.6% (n = 11) and in 12.5% (n = 7). 32 patients were not evaluable (57.1%). Median treatment duration was 6.1 months. Treatment related AE were reported in 76.8% (n = 43) and 19.6% (n = 11) had grade 3-5. Fatigue (26.8%), diarrhea (26.8%) and hand-foot-syndrome (25.0%) were the 3 most frequent AEs of any grade and causality. SAE were reported in 21.4% (n = 12), 2 were fatal. Major limitation was the retrospective data capture in our study. ConclusionsCabozantinib followed directly after ICI-based therapy was safe and feasible. No new safety signals were reported. A lower starting dose was frequently utilized in this real-world cohort, which was associated with a favorable tolerability profile. Our data supports the use of cabozantinib after ICI treatment.

Preprocedural assessment of coronary artery disease in patients undergoing transcatheter aortic valve implantation: Rationale and design of the EASE-IT CT registry.

Invasive coronary angiography (ICA) is the standard for pre-procedural assessment of coronary artery disease (CAD) in patients undergoing transcatheter aortic valve implantation (TAVI). However, it requires hospitalization and can be associated with complications. Computed tomography angiography (CTA) may be a viable alternative to rule out prognostically relevant CAD. The EASE-IT CT Registry is an investigator-initiated, prospective, observational, multicentre pilot registry involving patients aged ≥75 years with severe aortic stenosis (AS) intended to implant a transcatheter heart valve (THV) of the SAPIEN family. A total of 150 patients will be recruited from four sites in Germany and Austria. The registry will consist of two prospective cohorts: the investigational CTA-only cohort and the CTA + ICA control cohort. The CTA-only cohort will enrol 100 patients in whom significant (≥50%) left main (LM) and/or proximal left anterior descending artery (LAD) stenosis are ruled out on CTA. The CTA + ICA control cohort will enrol 50 patients who have undergone both CTA and ICA before TAVI and in whom ≥50% LM/proximal LAD stenosis has been ruled out by CTA. Three composite endpoints will be assessed at 3 months post-TAVI: CAD-specific endpoints, VARC-3-defined device success and early safety. The EASE-IT CT Registry evaluates whether TAVI can be carried out safely without performing ICA if prognostically relevant CAD of the LM/proximal LAD is ruled out with CTA. If so, the omission of ICA would help streamline the pre-procedural workup of TAVI patients.

Prospective randomized multicenter phase III trial comparing perioperative chemotherapy (FLOT protocol) to neoadjuvant chemoradiation (CROSS protocol) in patients with adenocarcinoma of the esophagus (ESOPEC trial).

LBA1 Background: The most effective multimodal approach for treatment of resectable locally advanced esophageal adenocarcinoma (EAC) is under debate. A prior ranking question is if neoadjuvant chemoradiation therapy or perioperative chemotherapy is superior. ESOPEC (NCT02509286) is a multicenter prospective randomized trial comparing neoadjuvant CROSS (41.4Gy plus carboplatin/paclitaxel) followed by surgery versus perioperative FLOT (5-FU/ leucovorin/oxaliplatin/docetaxel) and surgery for the curative treatment of EAC. Methods: Patients with cT1 cN+ cM0 or cT2-4a cNany cM0 resectable EAC were eligible. The primary endpoint is overall survival (OS; 90% power; hazard ratio [HR] 0.645, 218 events needed; one sided significance level of 2.5%). Analysis is by intention-to-treat in all randomized patients. The effect of treatment on OS is estimated using Cox regression stratified by study site, and including N stage (N0, N+), and age as covariates. Results: Between Feb 2016 and Apr 2020, 438 patients from 25 sites in Germany were randomly assigned to two treatment groups (221 FLOT; 217 CROSS). Baseline characteristics (male sex 89.3%, median age 63 [range 30-86], cT3/4 80.5%; cN+ 79.7%) were well balanced between both arms. Neoadjuvant treatment was started in 403 patients (207 FLOT; 196 CROSS). Surgery was done in 371 patients (191 FLOT; 180 CROSS). R0 resection was achieved in 351 patients (180 FLOT; 171 CROSS). 90 days postsurgical mortality was 4.3% (3.2% FLOT; 5.6% CROSS). After a median follow up of 55 months, 218 patients had died (97 FLOT; 121 CROSS). Median OS was 66 (95% CI 36 – not estimable) months in the FLOT arm, and 37 (95% CI 28 – 43) months in the CROSS arm. The 3-year OS rates were 57.4% (95% CI 50.1 – 64.0%) for FLOT and 50.7% (95% CI 43.5 – 57.5%) for CROSS (HR 0.70, 95% CI 0.53-0.92, p=0.012). In 359 patients with available tumor regression status, pathological complete response was achieved in 35 (19.3%, 95%-CI 13.9 – 25.9%) in FLOT and in 24 (13.5%, 95%-CI 8.8 – 19.4%) in CROSS. Conclusions: Perioperative FLOT improves survival in resectable EAC compared to neoadjuvant CROSS. Funding: The trial was funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation), project number 264590883. Clinical trial information: NCT02509286 .

Treatment exit options for non-infectious uveitis registry: participant characteristics at 3 years

PurposeThe Treatment exit Options For non-infectious Uveitis (TOFU) registry documents disease courses for non-anterior non-infectious uveitis entities with and without treatment to generate more evidence for clinical management recommendations including...

Type 1 Myocardial Infarction in Patients With Acute Ischemic Stroke

Elevated values of high-sensitivity cardiac troponin (hs-cTn) are common in patients with acute ischemic stroke and are associated with poor prognosis. However, diagnostic and therapeutic implications in patients with ischemic stroke remain unclear. To identify factors indicative of myocardial infarction (MI) in patients with acute ischemic stroke and hs-cTn elevation. The primary hypothesis was that a dynamic change of hs-cTn values (>50% change) in patients with acute ischemic stroke indicates MI. This cross-sectional study was a prospective, observational study with blinded end-point assessment conducted across 26 sites in Germany. Patients were included if they had acute ischemic stroke within 72 hours and either (1) highly elevated hs-cTn values on admission (>52 ng/L) or (2) hs-cTn levels above the upper limit of normal and a greater than 20% change at repeated measurements. Patients were enrolled between August 2018 and October 2020 and had 1 year of follow-up. Statistical analysis was performed between April 2022 and August 2023. Standardized electrocardiography, echocardiography, and coronary angiography. Diagnosis of MI as adjudicated by an independent end-point committee based on the findings of electrocardiography, echocardiography, and coronary angiography. In total, 254 patients were included. End points were adjudicated in 247 patients (median [IQR] age, 75 [66-82] years; 117 were female [47%] and 130 male [53%]). MI was present in 126 of 247 patients (51%) and classified as type 1 MI in 50 patients (20%). Dynamic change in hs-cTn value was not associated with MI in univariable (32% vs 38%; χ2 P = .30) or adjusted comparison (odds ratio, 1.05; 95% CI, 0.31-3.33). The baseline absolute hs-cTn value was independently associated with type 1 MI. The best cutoffs for predicting type 1 MI were at hs-cTn values 5 to 10 times the upper limit normal. This study found that in patients with acute ischemic stroke, a dynamic change in hs-cTn values did not identify MI, underscoring that dynamic changes do not identify the underlying pathophysiological mechanism. In exploratory analyses, very high absolute hs-cTn values were associated with a diagnosis of type 1 MI. Further studies are needed how to best identify patients with stroke who should undergo coronary angiography.

Comparison of Drivetrain Vibration Response During Field Operation and on a Nacelle Test Bench

Nacelle test benches offer the chance to identify any possible issues in the system design before conducting mandatory field testing for type certification. This can potentially reduce costs and time to market. However, nacelle system testing is an abstraction of the real system, as several interactions and interfaces between the nacelle and its environment are absent. Consequently, this has initiated research studies in recent years to fully understand the influence of these abstractions on the device under test. Extensive research has been conducted on the recently completed project Testfeld BHV to understand the influence of abstractions on the vibration response of the drivetrain. In this project, the Adwen AD8-180 has been the wind turbine under study that was tested first at a nacelle test bench, followed by field tests at a site in Germany. This paper presents the findings of these studies with regards to the drivetrain vibration response during nacelle tests and field tests. The similarities and differences observed in the drivetrain vibration response are highlighted, and reasons that lead to deviations in the vibration response are discussed. Furthermore, the work also presents a simulative framework that can aid the test bench’s ability to predict the correct field-like drivetrain vibration response prior to field tests.

Petrophysical Analyses for Supporting the Search for a Claystone-Hosted Nuclear Repository

The Bundesgesellschaft für Endlagerung mbH (BGE; “Federal Company for Radioactive Waste Disposal”) is responsible for identifying a repository site in Germany for the storage of high-level radioactive waste, ensuring the best possible safety for at least 1 million years (StandAG, 2017). The three-phase site selection process is currently in Step 2 of its Phase I. Around 90 potentially suitable sub-areas are evaluated via individual representative preliminary safety assessments. These sub-areas cover all types of potential containment rock: allochthonous and autochthonous rock salt, claystone, and crystalline rock. Such a comprehensive assessment is challenging for a host rock that covers vast areas like claystone or autochthonous salt. One of the steps towards estimating parameters for a site search process requires the analysis of numerous logs from the areas of interest and their vicinity. Unfortunately, computing these parameters is a much more complex problem than it seems. While gamma ray logs have been the petrophysicist’s workhorse for decades, they allow no quantification of clay properties. Nuclear magnetic resonance and neutron activation logs yield critical information but are scarce in old wells. Decades of research have given good algorithms for defining wet clay porosity from resistivity logs, but inverting those for porosity and tortuosity remains challenging. Another log-derived parameter is a formation’s homogeneity, which quantifies the jaggedness of a logging curve. A vertical variogram or variable filter technique can accomplish this.

Effect of Season and Machine Type on Performance of Semi- and Fully Mechanized Harvesting Systems in Beech-Dominated Stands

It is common to have large trees in mature hardwood-dominated stands. This is especially true for European beech (Fagussylvatica L.), which can also have a complex architecture. Such trees have predominantly been harvested using motor-manual operations. However, in an effort to increase occupational safety and allow for a more continuous wood flow to processing facilities, fully-mechanized systems are also being employed more frequently. This study was established to determine the effect of season (Fall or Winter) and harvester type (wheeled or tracked) on the performance of semi- and fully- mechanized harvesting systems deployed in beech-dominated stands. Time-and-motion analysis was conducted on a total of 927 trees located in two forest sites in Germany. The study indicated that new silvicultural prescriptions make it impossible to harvest all trees exclusively with mechanized systems, even in the case of the tracked harvester with its 14.5 m boom. Motor-manual intervention was needed with trees that were too large, malformed or out of reach. Motor-manual intervention was significantly more frequent for the wheeled (30%) than for the tracked harvester (18%). Once again, tree size had the strongest effect on time consumption in a linear model, which varied from 0.5 to over 6 min per tree. Season and machine effect were also significant but could only account for a small fraction of the total variability. For the same tree size, time consumption was higher with the wheeled harvester and during the fall. The model also indicated a significant relationship between tree form and time consumption, even though the explanatory contribution of this independent variable was relatively small, too. Good stem form resulted in a lower time consumption. The larger tracked harvester was generally more efficient, but also more expensive to own and operate: its higher costs must be weighed against the higher revenues. New silvicultural trends make it difficult to achieve full mechanization, but the results of this study may guide managers towards technical solutions that minimize motor-manual intervention to the advantage of higher productivity and better occupational safety.