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Aims: Tumour content in prostatic biopsies is an important indicator of prostate cancer volume and patient prognosis. Consequently, guidelines typically recommend reporting it as a percentage or linear length (mm). This study aimed to determine the current practices for reporting tumour content in prostatic biopsies and evaluated the consistency among pathologists in diagnosing 10 standard biopsy cases of prostate cancer to assess interobserver variability., Methods and Results: A web-based survey gathered data on demographics, experience and attitudes regarding the reporting of prostate cancer and its extent in biopsies. Virtual microscopy allowed analysis of 10 biopsy cases, each consisting of a single slide of prostate cancer. Self-reports from 304 participants recruited via the International Society of Urological Pathology and the German Society of Pathology were analysed. Most participants (43.4%) reported tumour extent as percentage of the biopsy core, 37.6% reported percentages and mm and 18.3% reported mm exclusively. The methods used to determine percentages showed an unexpected spread of choices, leading to considerable variability in results. Additionally, 40.8% of participants took part in the practical segment of the survey. The reported measures of tumour extent confirmed a notable interobserver variability, which was significantly higher for reported percentages., Conclusion: A high rate of interobserver variability in reporting tumour content in prostatic biopsies was found. This matter is especially critical for patients who are candidates for active surveillance. Reporting absolute measures of tumour content has the advantage of lower variability in comparison to percentages., (© 2024 The Author(s). Histopathology published by John Wiley & Sons Ltd.)

Purpose: Prophylactic insertion of an external ventricular drainage (EVD) prior to the resection of posterior fossa metastases (PFMs) is a common approach to address postoperative transient and permanent hydrocephalus. However, predicting surgery-related hydrocephalus in the preoperative phase continues to be a challenge. This study aims to analyze the incidence, preoperatively collectable risk factors and necessity of perioperative external ventricular drainage placement after posterior fossa metastasis surgery., Methods: All patients undergoing surgery for PFMs at the authors' neuro-oncological center between 2015 and 2021 were identified and assessed for postoperative hydrocephalus occurrence. Tumour volume, edema volume, and 4th ventricle volume were assessed on preoperative magnetic resonance imaging scans using the IntelliSpace Portal 5.0. A multivariable logistic regression analysis was performed to identify possible predictors for postoperative hydrocephalus occurrence., Results: Postoperative hydrocephalus occurred in 14 of the 130 identified PFM patients (11%). Multivariable analysis and receiver operating characteristic (ROC) analysis revealed a 4th -ventricle-to-tumor-volume ratio ≤ 0.02 (OR 33.1, 95% CI 3.8-284.3, p = 0.001), an edema-to- tumor-volume ratio ≤ 0.85 (OR 10.6, 95% CI 2.4-47.4, p = 0.002), an imaging-morphological contact to the 4th ventricle (OR 5, 95% CI 1.4-18, p = 0.013), and multiple intracranial metastases (OR 2.4, 95% CI 1-5.9, p = 0.045) as independent predictors for surgery-related postoperative hydrocephalus occurrence., Conclusion: The present study identifies preoperatively detectable risk factors for the occurrence of postoperative hydrocephalus following surgery for PFMs. These findings may provide guidance in clinical decision-making regarding prophylactic EVD placement., Competing Interests: Declarations. Ethics approval: This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Ethics Committee of the University Hospital Bonn (No. 250/19). Consent to participate: Informed consent was not sought as a retrospective study design was used. Consent to publish: All authors agreed to the publication of the manuscript. Previous publication: None. Previous presentations: Data included in this manuscript have been presented in part at the 75h national day of Deutsche Gesellschaft für Neurochirurgie/German Society of Neurosurgery (DGNC) in Göttingen 06/2024 and sections day of Sektionstagung Deutsche Gesellschaft für Neurochirurgie/German Society of Neurosurgery (DGNC) 09/2024. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background/aims: Bleb characteristics in the area around the plate following glaucoma drainage device (GDD) surgery are difficult to evaluate on slit lamp examination. Ultrasound sonography could be used for more detailed visualisation. The aim of this study was to describe bleb configuration after PAUL glaucoma implant (PGI) surgery and evaluate the possible correlation with intraocular pressure (IOP) in order to derive new markers for evaluating GDD function., Methods: Patients underwent a 15 MHz ultrasound examination (Compact Touch, Quantel Medical) after undergoing PGI implantation. The filtering bleb dimensions were measured and bleb configuration was assessed along with documentation of all clinical data., Results: A total of 70 eyes from 65 patients were included. 55 eyes (78.6%) had a double-layered bleb whereas 15 eyes (21.4%) had a bleb with only one compartment (six eyes, 8.6% above; nine eyes, 12.9% below the plate). The total height of both compartments averaged 3.52 mm. The average IOP was 13.03 mm Hg. There was a significant correlation between single and double-layered blebs (p<0.01) with regard to IOP (one compartment: 16.47 mm Hg vs two compartments: 12.09 mm Hg). There was no significant correlation between total bleb height (p=0.143) or bleb extension (T: p=0.629; L: p=0.742). However, total bleb height showed an inverse association with IOP. Blebs with a height >2 mm had significantly lower mean IOP than those having <2 mm bleb heights (p=0.041)., Conclusions: Sonography is a suitable modality to evaluate bleb characteristics after PGI implantation. Blebs with a double fluid layer are significantly correlated with lower IOP values. Bleb height has an inverse association with IOP, with higher blebs (>2 mm) showing a significantly lower IOP., Competing Interests: Competing interests: CW, LW, MP and RL certify that they have no affiliations with or involvement in any organisation or entity with any financial interest (such as honoraria; educational grants; participation in speakers’ bureaus; membership, employment, consultancies, stock ownership or other equity interest and expert testimony or patent-licensing arrangements) or non-financial interest (such as personal or professional relationships, affiliations, knowledge or beliefs) in the subject matter or materials discussed in this manuscript. KM has received honoraria or research grants from the following: Allergan/Abbvie (C,H,R) and Glaukos (C,H,R), but none of this is related to the current study. FGH has received honoraria or research grants from the following: Acucela (C,F), Allergan (F), Apellis (C, F), Bayer (C, F), Boehringer-Ingelheim (C), Bioeq/ Formycon (F,C), CenterVue (F), Ellex (F), Roche/Genentech (C,F), Geuder (C,F), Graybug (C), Gyroscope (C), Heidelberg Engineering (C,F), IvericBio (C, F), Kanghong (C,F), LinBioscience (C), NightStarX (F), Novartis (C,F), Optos (F), Oxurion (C), Pixium Vision (C,F), Oxurion (C), Stealth BioTherapeutics (C), Zeiss (F,C), but none of this is related to the current study., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ Group.)

Purpose: The relative ellipsoid zone reflectivity (rEZR) is an innovative biomarker for photoreceptor alterations and showed association with disease staging in macular telangiectasia type 2 (MacTel). However, its prognostic relevance for the ellipsoid zone (EZ) loss is unclear., Methods: Longitudinal spectral-domain optical coherence tomography (SD-OCT) imaging of patients with MacTel from an observational natural history study was used for en face determination of manifest EZ loss. The rEZR was assessed globally (mean rEZR/SD-OCT volume scan) and topographically (spatially refined). Logistic and linear-mixed effect models were used to investigate the rEZR's association with EZ loss onset and the (square-root transformed) progression rate of existing EZ loss., Results: A total of 97 eyes of 70 patients (39 women, mean age = 60.3 ± 8.9 years) were included and reviewed in a median observational period of 28.7 months (range = 20.3-49.9 months). Whereas 65 eyes of 44 patients showed manifest EZ loss (mean ± SD area = 0.44 ± 0.57 mm2) at baseline, 14 eyes of 14 patients developed EZ loss over time. Significant associations of the rEZR were only found in the topographical analyses indicated by lower rEZR values and a higher risk for EZ loss onset (odds ratio [OR] = 0.34, 95% confidence interval [CI] = 0.29 to 0.39, P < 0.001) as well as a faster EZ loss progression (coefficient estimate = -0.002, 95% CI = -0.0046 to 0.0001, P = 0.038)., Conclusions: This study demonstrates the prognostic relevance of spatially refined rEZR changes before and beyond already existing EZ loss for both its onset and progression over time in MacTel. Further analyses of the rEZR are warranted to achieve both a more tailored patient selection and a novel end point identification for clinical trials in MacTel.

Objectives: To assess the prognostic value of cardiac MRI (CMR) parameters for the occurrence of major adverse cardiac events (MACE) in patients with infarct-like myocarditis., Methods: In this retrospective single-center study, patients with CMR-confirmed acute myocarditis with infarct-like presentation were identified (2007-2020). Functional and structural parameters were analyzed including late gadolinium enhancement (LGE). The primary endpoint was the occurrence of MACE up to 5 years after discharge., Results: In total, 130 patients (mean age, 40 ± 19 years; 97 men, 75%) with infarct-like myocarditis were included. CMR was conducted a median of 3 days (interquartile range [IQR], 1-5) after symptom onset. MACE occurred in 18/130 patients (14%) during a median follow-up of 19.3 months (IQR, 4.5-53). The median extent of LGE was 7% (IQR, 4-10). LGE affected the subepicardium in 111/130 patients (85%), the midwall in 45/130 patients (35%), and both the subepicardium and midwall in 27/130 patients (21%). Transmural extension of non-ischemic LGE lesions was observed in 15/130 patients (12%) and septal LGE in 42/130 patients (32%). In univariable Cox regression analysis, a significant association was found between the occurrence of MACE and both, quantified LGE extent and transmural LGE pattern. In multivariable analysis, transmural extension of LGE was an independent predictor for MACE (hazard ratio, 6.34; 95% confidence interval: 2.29-17.49; p < 0.001). Patients with the transmural extension of LGE had a shorter event-free time on Kaplan-Meier analysis (log-rank p < 0.001)., Conclusions: MACE occurred in 14% of patients with infarct-like myocarditis during follow-up. A transmural extension of non-ischemic LGE was associated with a worse long-term prognosis., Critical Relevance Statement: CMR-based assessment of transmural extension of non-ischemic LGE holds the potential to serve as an easily assessable marker for risk stratification in patients with infarct-like myocarditis., Key Points: The prognostic value of CMR was studied in patients with infarct-like myocarditis. The extent of LGE and transmural extension were linked to adverse cardiac events. Transmural non-ischemic LGE can serve as an easily assessable prognostic marker., (© 2024. The Author(s).)

The histopathological examination of radical prostatectomy specimens is essential for assessing critical tumor characteristics, including stage, grade, and margins, all of which impact patient prognosis. However, the extent of embedding the prostate has long been a subject of debate, with some advocating partial/selective embedding and others favoring complete embedding. This study establishes a standardized and time-efficient protocol for processing radical prostatectomy specimens with limited embedding while maintaining diagnostic accuracy. Two hundred twenty-six prostatectomy specimens were analyzed, and the results of a highly standardized selective embedding protocol, systematically embedding the apex, the base, the transition to the seminal vesicles, and selected horizontal sections, were compared with full embedding as the gold standard. Non-inferiority testing was conducted by one-sided binomial tests and Pearson-Clopper confidence intervals. Selective embedding provided consistent and accurate diagnostic information with up to 90-98% concordance in pT, margins, ISUP-grade groups, and presence of IDC-P and cribriform tumor growth. In summary, this study establishes an economical standardized protocol for selective embedding of radical prostatectomy specimens with only minimal loss of information., (© 2024. The Author(s).)

Ki-67, a nuclear protein expressed in all stages of cellular proliferation, is a valuable tool to assess tumor proliferation and has been linked to more aggressive tumor behavior. However, interlaboratory staining heterogeneity and inter-observer variability challenge its reproducibility. Round Robin tests are a suitable tool to standardize and harmonize immunohistochemical and molecular analyses in histopathology. The study investigates the interrater and interlaboratory reproducibility of Ki-67-scoring using both manual and automated approaches. Unstained TMA slides comprising diverse tumor types (breast cancer, neuroendocrine tumors, lymphomas, and head and neck squamous cell carcinoma) were distributed to six pathology laboratories, each employing their routine staining protocols. Manual and automated scoring methods were applied, and interrater and interlaboratory agreement assessed using intraclass correlation coefficients (ICC). The results highlight good-to-excellent reliability overall, with automated scoring demonstrating higher consistency (ICC 0.955) than manual scoring (ICC 0.871). Results were more variable when looking at the individual entities. Reliability remained good for lymphomas (ICC 0.878) and breast cancer (ICC 0.784) and was poor in well-differentiated neuroendocrine tumors (ICC 0.354). This study clearly advocates standardized practices and training to ensure consistency in Ki-67-assessment, and it demonstrates that this can be achieved in a peer-to-peer approach in local quality-circles., (© 2024 The Author(s). APMIS published by John Wiley & Sons Ltd on behalf of Scandinavian Societies for Pathology, Medical Microbiology and Immunology.)

Background/objectives: Metabolic dysfunction-associated steatotic liver disease (MASLD) is closely associated with obesity and insulin resistance (IR). Identifying characteristics that predict a higher risk of fibrosis using noninvasive methods is particularly important., Methods: We performed a secondary analysis of data from an RCT of 48 patients after one anastomosis gastric bypass (OAGB) surgery, supplemented with specifically formulated probiotics and micronutrients or control treatment for 12 weeks. Patients were categorized using alanine aminotransferase (ALAT; >35 U/L for women, >50 U/L for men), higher NAFLD fibrosis score (NFS) > -1.455), and IR (HOMA-IR > 2.0). This trial was registered at Clinicaltrials.gov (ID: NCT03585413)., Results: Abnormal ALAT was associated with high triglycerides, blood pressure (BP), glucose, and fatty liver index (FLI). NFS > -1.455 was linked to higher age, body mass, waist circumference, and FLI, and lower albumin and platelet count. HOMA-IR > 2.0 was associated with higher BP and triglycerides, lower HDL-cholesterol, higher serum transaminases, and higher probabilities of steatosis and fibrosis. Twelve weeks postoperatively, patients with NFS > -1.455 showed greater reductions in body mass, systolic BP, serum insulin, and HbA1c, whereas those with NFS ≤ -1.455 showed improvements in FLI and lipid metabolism but had high glucose concentrations. Patients with HOMA-IR ≤ 2.0 also had high glucose concentrations., Conclusions: The evaluation of common biomarker scores for fibrosis and IR may help clinicians to recognize severe NAFLD and improve the outcomes of OAGB surgery.

Background: Pseudoxanthoma elasticum (PXE) is a rare, inherited disease characterised by specific skin lesions, progressive loss of vision and early onset atherosclerosis. Atherosclerosis in PXE leads to an increased rate of vascular occlusion and severe intermittent claudication. Although genetically determined, the individual course of PXE is highly variable. Up to now, there is no sufficient parameter to identify individuals at risk of rapid disease progression. This present study focused the lipid profile of patients with PXE and its possible influence on the clinical severity of peripheral artery disease (PAD). Patients and methods: The lipid profile of patients with PXE was unremarkable (TGC: 135.8±105.8 mg/dl; TC: 172.5±44.4 mg/dl; HDL: 63.0±18.2 mg/dl; Lp[a]: 64.7±93.5 nmol/l). Ordinal regression showed a significant association of Lp(a) with the severity of PAD with an odds ratio of 1.01 (1.00-1.02; p = 0.004), whereas the other fractions of the lipid profile had no significant influence. Results: The lipid profile of patients with PXE was unremarkable (TGC: 135.8±105.8 mg/dl; TC: 172.5±44.4 mg/dl; HDL: 63.0±18.2 mg/dl; Lp[a]: 64.7±93.5 nmol/l). Ordinal regression showed a significant association of Lp(a) with the severity of PAD with an odds ratio of 1.01 (1.00-1.02; p = 0.004), whereas the other fractions of the lipid profile had no significant influence. Conclusions: This study provides the largest evaluation of blood lipids up to now and the first characterization of Lp(a) levels in patients with PXE. We were able to provide first evidence of a correlation between elevated levels of Lp(a) and the severity of PAD. The present results suggest that determination of Lp(a) in early stages of PXE could help to identify patients at risk of rapid disease progression and with the need of intensified walking exercise training.

Objective: Informative biomarkers are an urgent need in the management of amyotrophic lateral sclerosis. Serum cardiac troponin T is elevated in the majority of amyotrophic lateral sclerosis patients and increases with disease progression. We sought to establish the informative value of cardiac troponin T with regard to respiratory function, a major prognostic factor in amyotrophic lateral sclerosis., Methods: In this retrospective observation, we analyzed two independent hospital-based cohorts (d = discovery cohort; v = validation cohort) regarding serum cardiac troponin T (n d  = 298; n v  = 49), serum neurofilament light chain (n d  = 117; n v  = 17), and respiratory tests (n d  = 93; n v  = 49)., Results: Serum cardiac troponin T, in contrast to serum neurofilament levels, was associated with the respiratory domain of the revised amyotrophic lateral sclerosis functional rating scale and with pulmonary function parameters, namely forced vital capacity % (r = -0.45, p = 0.001) and slow vital capacity % (r = -0.50, p = 0.001). Serum cardiac troponin T reliably discriminated benchmarks of slow vital capacity <80% (AUC 0.73, 95% CI 0.62-0.84) and <50% (AUC 0.80, 95% CI 0.68-0.93), forced vital capacity <80% (AUC 0.72, 95% CI 0.61-0.83) and <50% (AUC 0.79, 95% CI 0.67-0.91)., Interpretation: Our findings position cardiac Troponin T as a valuable serum biomarker in amyotrophic lateral sclerosis, complementing neurofilaments and expanding the understanding of underlying physiological mechanisms. In clinical practice, serum cardiac troponin T can flag benchmarks of compromised respiratory function., (© 2024 The Author(s). Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Purpose: Inflammatory changes in epicardial (EAT) and pericardial adipose tissue (PAT) are associated with increased overall cardiovascular risk. Using routine, preinterventional cardiac CT data, we examined the predictive value of quantity and quality of EAT and PAT for outcome after transcatheter aortic valve replacement (TAVR)., Materials and Methods: Cardiac CT data of 1197 patients who underwent TAVR at the in-house heart center between 2011 and 2020 were retrospectively analyzed. The amount and density of EAT and PAT were quantified from single-slice CT images at the level of the aortic valve. Using established risk scores and known independent risk factors, a clinical benchmark model (BMI, Chronic kidney disease stage, EuroSCORE 2, STS Prom, year of intervention) for outcome prediction (2-year mortality) after TAVR was established. Subsequently, we tested whether the additional inclusion of area and density values of EAT and PAT in the clinical benchmark model improved prediction. For this purpose, the cohort was divided into a training (n=798) and a test cohort (n=399)., Results: Within the 2-year follow-up, 264 patients died. In the training cohort, particularly the addition of EAT density to the clinical benchmark model showed a significant association with outcome (hazard ratio 1.04, 95% CI: 1.01-1.07; P =0.013). In the test cohort, the outcome prediction of the clinical benchmark model was also significantly improved with the inclusion of EAT density (c-statistic: 0.589 vs. 0.628; P =0.026)., Conclusions: EAT density as a surrogate marker of EAT inflammation was associated with 2-year mortality after TAVR and may improve outcome prediction independent of established risk parameters., Competing Interests: The authors declare no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Patients are increasingly using Generative Pre-trained Transformer 4 (GPT-4) to better understand their own radiology findings., Purpose: To evaluate the performance of GPT-4 in transforming cardiovascular magnetic resonance (CMR) reports into text that is comprehensible to medical laypersons., Methods: ChatGPT with GPT-4 architecture was used to generate three different explained versions of 20 various CMR reports (n = 60) using the same prompt: "Explain the radiology report in a language understandable to a medical layperson". Two cardiovascular radiologists evaluated understandability, factual correctness, completeness of relevant findings, and lack of potential harm, while 13 medical laypersons evaluated the understandability of the original and the GPT-4 reports on a Likert scale (1 "strongly disagree", 5 "strongly agree"). Readability was measured using the Automated Readability Index (ARI). Linear mixed-effects models (values given as median [interquartile range]) and intraclass correlation coefficient (ICC) were used for statistical analysis., Results: GPT-4 reports were generated on average in 52 s ± 13. GPT-4 reports achieved a lower ARI score (10 [9-12] vs 5 [4-6]; p < 0.001) and were subjectively easier to understand for laypersons than original reports (1 [1] vs 4 [4,5]; p < 0.001). Eighteen out of 20 (90%) standard CMR reports and 2/60 (3%) GPT-generated reports had an ARI score corresponding to the 8th grade level or higher. Radiologists' ratings of the GPT-4 reports reached high levels for correctness (5 [4, 5]), completeness (5 [5]), and lack of potential harm (5 [5]); with "strong agreement" for factual correctness in 94% (113/120) and completeness of relevant findings in 81% (97/120) of reports. Test-retest agreement for layperson understandability ratings between the three simplified reports generated from the same original report was substantial (ICC: 0.62; p < 0.001). Interrater agreement between radiologists was almost perfect for lack of potential harm (ICC: 0.93, p < 0.001) and moderate to substantial for completeness (ICC: 0.76, p < 0.001) and factual correctness (ICC: 0.55, p < 0.001)., Conclusion: GPT-4 can reliably transform complex CMR reports into more understandable, layperson-friendly language while largely maintaining factual correctness and completeness, and can thus help convey patient-relevant radiology information in an easy-to-understand manner., Competing Interests: Declaration of competing interests The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Alexander Isaak reports financial support was provided by BONFOR Research Commission of the Medical Faculty Bonn. The other authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Germany's high density of under-equipped hospitals and anticipated surge in orthopedic and trauma surgery-related diseases by 2030, combined with personnel shortages, are expected to increase patient transfers between hospitals, an issue that urgently needs standardized protocols. Despite some existing cooperative agreements, such as between joint-replacement centers or within the Trauma Network DGU ® , these measures do not adequately address the full range of patient-transfer cases, including those due to a lack of specialization or staff shortages, resulting in delayed treatment and potential health risks. This study aims to dissect the intricacies of interhospital transfers in orthopedics and trauma surgery across Germany, focusing on understanding the underlying reasons for transfers, comparing the operational structures of small and large hospitals, and laying the groundwork for future standardized protocols to enhance patient care., Material and Methods: A cross-sectional study was conducted in the form of an online survey via SoSci Survey, which was directed at orthopedic surgeons and trauma surgeons working in hospitals in Germany. The 22-question survey gathered information on participants' clinic roles, departmental details, transfer processes, frequent diagnoses, perceptions of transfer quality, and improvement areas. The survey was sent to orthopedic and trauma surgeons in Germany by the specialist society. The data were analyzed using descriptive and inferential statistics to ensure a comprehensive insight into interhospital transfer practices., Results: The study involved 152 participants from various hospital ranks and located in different hospital sizes and types across rural and urban areas. A significant difference was observed between the care structures of basic/regular care and central/maximum care hospitals, especially regarding the available facilities and specialties. These findings suggest improvements such as better patient documentation, increased digital communication, optimized patient distribution, and standardization of transfer requests, among others., Conclusions: This study highlights the urgent need for improved protocols and resource allocation to eliminate inequalities in transfers between hospitals in orthopedics and trauma surgery in Germany.

Background: Interstitial lung disease (ILD) comprises a wide variety of pulmonary parenchymal disorders within which progressive fibrosing ILD (PF-ILD) constitutes a phenotypic subset. By use of speckle tracking-based strain analysis we aimed to evaluate the degree of left ventricular (LV) dysfunction in progressive vs. non-progressive fibrosing ILD (non-PF-ILD)., Methods: A total of 99 ILD patients (mean age 63.7 ± 13.5 years, 37.4% female), composed of 50 PF-ILD and 49 non-PF-ILD patients, and 33 controls were prospectively enrolled and underwent conventional and speckle tracking echocardiography. Additional laboratory and pulmonary function testing, as well as six-minute walk test were performed., Results: As compared to the non-PF-ILD cohort, PF-ILD patients exhibited a significantly impaired forced vital capacity (2.4 ± 1.0l vs. 3.1 ± 0.9l, p = 0.002), diffusion capacity for carbon monoxide (DLCO, 25.6 ± 16.3% predicted vs. 43.6 ± 16.67% predicted, p <0.001) and exercise capacity response as measured by the six-minute walk test distance (268.1 ± 178.2m vs. 432.6 ± 94.2m, p <0.001). Contrary to conventional echocardiographic LV parameters, both regional and global longitudinal LV strain measurements were significantly altered in ILD patients as compared to controls. No differences in LV strain were found between both patient groups. Significant correlations were observed between global longitudinal strain, on the one hand, and systemic inflammation markers, total lung capacity (TLC) and DLCO, on the other hand (high-sensitivity C-reactive protein: Pearson´s r = -0.30, p< 0.001; interleukin-6: Pearson´s r = -0.26, p = 0.007; TLC % predicted: Pearson´s r = 0.22, p = 0.02; DLCO % predicted: Pearson´s r = 0.21, p = 0.02)., Conclusions: ILD is accompanied by LV dysfunction. LV functionality inversely correlates with the severity of the restrictive ventilatory defect and inflammation marker levels. These observations support the assumption of persistent low-grade systemic inflammation that may link systemic cardiovascular function to ILD status., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Stumpf et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction: Abortion is a crucial sexual and reproductive right. However, the legal situation of pregnancy termination is rather heterogeneous across countries and regions. The political climate and cultural perception may result in abortion-related stigma. This mixed-methods systematic review protocol aims to detail the proposed methods for assessing the current state of research on abortion stigma in high-income countries from an abortion seeker, healthcare provider and public perspective., Methods and Analysis: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocols guideline, we conducted a systematic literature search of peer-reviewed studies from high-income countries in relevant electronic databases: PubMed, CINHAL, PsycINFO, LIVIVO and Cochrane Library. Qualitative, quantitative and mixed-method studies that measured or examined abortion-related stigma in abortion seekers, healthcare professionals and the general public will be included. Assessment of risk of bias, data synthesis and qualitative meta-aggregation will be carried out., Ethics and Dissemination: The results of the systematic review will be submitted to peer-reviewed journals and presented at relevant conferences., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Blood biomarkers accurately identify Alzheimer's disease (AD) pathophysiology and axonal injury. We investigated the influence of food intake on AD-related biomarkers in cognitively healthy, obese adults at high metabolic risk., Methods: One-hundred eleven participants underwent repeated blood sampling during 3 h after a standardized meal (postprandial group, PG). For comparison, blood was sampled from a fasting subgroup over 3 h (fasting group, FG). Plasma neurofilament light (NfL), glial fibrillary acidic protein (GFAP), amyloid-beta (Aβ) 42/40, phosphorylated tau (p-tau) 181 and 231, and total-tau were measured via single molecule array assays., Results: Significant differences were found for NfL, GFAP, Aβ42/40, p-tau181, and p-tau231 between FG and PG. The greatest change to baseline occurred for GFAP and p-tau181 (120 min postprandially, p < 0.0001)., Conclusion: Our data suggest that AD-related biomarkers are altered by food intake. Further studies are needed to verify whether blood biomarker sampling should be performed in the fasting state., Highlights: Acute food intake alters plasma biomarkers of Alzheimer's disease in obese, otherwise healthy adults. We also found dynamic fluctuations in plasma biomarkers concentration in the fasting state suggesting physiological diurnal variations. Further investigations are highly needed to verify if biomarker measurements should be performed in the fasting state and at a standardized time of day to improve the diagnostic accuracy., (© 2023 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Background: While inter-hospital transfers for patients who have suffered major trauma have been well investigated, patient flows for other injured patients, or cases with orthopedic complications, are rarely described. This study aims to analyze the affected collective and to show possible reasons, patterns, and pitfalls to optimize the process in future., Materials and Methods: In a prospective cohort study, all consecutive transfers to a Level I trauma center in Germany were documented and assessed. Patients suffering a major trauma were excluded. Data on the primary treating hospital, patient characteristics, and differences between emergency and elective surgery were analyzed., Results: A total of 227 patients were included; 162 were injured, while 65 had suffered a complication after elective orthopedic surgery or had a complex orthopedic pathology. The most common diagnoses leading to transfer were pathologies of the extremities (n = 62), pathologies of the spine (n = 50), and infections (n = 18). The main reasons stated by the transferring hospitals were a lack of expertise (137 cases) and a lack of capacity (43 cases). There was a significantly higher rate of transfers due to trauma (n = 162) than for orthopedic patients (n = 65), p < 0.0001., Conclusion: There is currently no structured procedure or algorithm for transferring patients in orthopedics and trauma surgery., (© 2023. The Author(s).)

Recent years have seen the development of many novel scoring tools for disease prognosis and prediction. To become accepted for use in clinical applications, these tools have to be validated on external data. In practice, validation is often hampered by logistical issues, resulting in multiple small-sized validation studies. It is therefore necessary to synthesize the results of these studies using techniques for meta-analysis. Here we consider strategies for meta analyzing the concordance probability for time-to-event data ("C-index"), which has become a popular tool to evaluate the discriminatory power of prediction models with a right-censored outcome. We show that standard meta-analysis of the C-index may lead to biased results, as the magnitude of the concordance probability depends on the length of the time interval used for evaluation (defined e.g., by the follow-up time, which might differ considerably between studies). To address this issue, we propose a set of methods for random-effects meta-regression that incorporate time directly as covariate in the model equation. In addition to analyzing nonlinear time trends via fractional polynomial, spline, and exponential decay models, we provide recommendations on suitable transformations of the C-index before meta-regression. Our results suggest that the C-index is best meta-analyzed using fractional polynomial meta-regression with logit-transformed C-index values. Classical random-effects meta-analysis (not considering time as covariate) is demonstrated to be a suitable alternative when follow-up times are small. Our findings have implications for the reporting of C-index values in future studies, which should include information on the length of the time interval underlying the calculations., (© 2023 The Authors. Research Synthesis Methods published by John Wiley & Sons Ltd.)

Background Deep learning (DL) reconstructions can enhance image quality while decreasing MRI acquisition time. However, DL reconstruction methods combined with compressed sensing for prostate MRI have not been well studied. Purpose To use an industry-developed DL algorithm to reconstruct low-resolution T2-weighted turbo spin-echo (TSE) prostate MRI scans and compare these with standard sequences. Materials and Methods In this prospective study, participants with suspected prostate cancer underwent prostate MRI with a Cartesian standard-resolution T2-weighted TSE sequence (T2 C ) and non-Cartesian standard-resolution T2-weighted TSE sequence (T2 NC ) between August and November 2022. Additionally, a low-resolution Cartesian DL-reconstructed T2-weighted TSE sequence (T2 DL ) with compressed sensing DL denoising and resolution upscaling reconstruction was acquired. Image sharpness was assessed qualitatively by two readers using a five-point Likert scale (from 1 = nondiagnostic to 5 = excellent) and quantitatively by calculating edge rise distance. The Friedman test and one-way analysis of variance with post hoc Bonferroni and Tukey tests, respectively, were used for group comparisons. Prostate Imaging Reporting and Data System (PI-RADS) score agreement between sequences was compared by using Cohen κ. Results This study included 109 male participants (mean age, 68 years ± 8 [SD]). Acquisition time of T2 DL was 36% and 29% lower compared with that of T2 C and T2 NC (mean duration, 164 seconds ± 20 vs 257 seconds ± 32 and 230 seconds ± 28; P < .001 for both). T2 DL showed improved image sharpness compared with standard sequences using both qualitative (median score, 5 [IQR, 4-5] vs 4 [IQR, 3-4] for T2 C and 4 [IQR, 3-4] for T2 NC ; P < .001 for both) and quantitative (mean edge rise distance, 0.75 mm ± 0.39 vs 1.15 mm ± 0.68 for T2 C and 0.98 mm ± 0.65 for T2 NC ; P < .001 and P = .01) methods. PI-RADS score agreement between T2 NC and T2 DL was excellent (κ range, 0.92-0.94 [95% CI: 0.87, 0.98]). Conclusion DL reconstruction of low-resolution T2-weighted TSE sequences enabled accelerated acquisition times and improved image quality compared with standard acquisitions while showing excellent agreement with conventional sequences for PI-RADS ratings. Clinical trial registration no. NCT05820113 © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Turkbey in this issue.

Purpose: Iodine deficiency increases the risk of cognitive impairment and delayed physical development in children. It is also associated with cognitive impairment in adults. Cognitive abilities are among the most inheritable behavioural traits. However, little is known about the consequences of insufficient postnatal iodine intake and whether the individual genetic disposition modifies the association between iodine intake and fluid intelligence in children and young adults., Methods: The cultural fair intelligence test was used to assess fluid intelligence in the participants of the DONALD study (n = 238; mean age, 16.5 [SD = 7.7] years). Urinary iodine excretion, a surrogate iodine intake marker, was measured in 24-h urine. Individual genetic disposition (n = 162) was assessed using a polygenic score, associated with general cognitive function. Linear regression analyses were conducted to determine whether Urinary iodine excretion was associated with fluid intelligence and whether this association was modified by individual genetic disposition., Results: Urinary iodine excretion above the age-specific estimated average requirement was associated with a five-point higher fluid intelligence score than that below the estimated average requirement (P = 0.02). The polygenic score was positively associated with the fluid intelligence score (β = 2.3; P = 0.03). Participants with a higher polygenic score had a higher fluid intelligence score., Conclusion: Urinary iodine excretion above the estimated average requirement in childhood and adolescence is beneficial for fluid intelligence. In adults, fluid intelligence was positively associated with a polygenic score for general cognitive function. No evidence showed that the individual genetic disposition modifies the association between Urinary iodine excretion and fluid intelligence., (© 2023. The Author(s).)

Objectives: To find simple imaging-based features on cardiac magnetic resonance (CMR) that are associated with major adverse cardiovascular events (MACE) in takotsubo syndrome (TTS)., Methods: Patients with TTS referred for CMR between 2007 and 2021 were retrospectively evaluated. Besides standard CMR analysis, commonly known complications of TTS based on expert knowledge were assessed and summarised via a newly developed PE 2 RT score (one point each for pleural effusion, pericardial effusion, right ventricular involvement, and ventricular thrombus). Clinical follow-up data was reviewed up to three years after discharge. The relationship between PE 2 RT features and the occurrence of MACE (cardiovascular death or new hospitalisation due to acute myocardial injury, arrhythmia, or chronic heart failure) was examined using Cox regression analysis and Kaplan-Meier estimator., Results: Seventy-nine patients (mean age, 68 ± 14 years; 72 women) with TTS were included. CMR was performed in a median of 4 days (IQR, 2-6) after symptom onset. Over a median follow-up of 13.3 months (IQR, 0.4-36.0), MACE occurred in 14/79 (18%) patients: re-hospitalisation due to acute symptoms (9/79, 11%) or chronic heart failure symptoms (4/79, 5%), and cardiac death (1/79, 1%). Patients with MACE had a higher PE 2 RT score (median [IQR], 2 [2-3] vs 1 [0-1]; p < 0.001). PE 2 RT score was associated with MACE on Cox regression analysis (hazard ratio per PE 2 RT feature, 2.44; 95%CI: 1.62-3.68; p < 0.001). Two or more PE 2 RT complications were strongly associated with the occurrence of MACE (log-rank p < 0.001)., Conclusions: The introduced PE 2 RT complication score might enable an easy-to-assess outcome evaluation of TTS patients by CMR., Key Points: • Complications like pericardial effusion, pleural effusion, right ventricular involvement, and ventricular thrombus (summarised as PE 2 RT features) are relatively common in takotsubo syndrome. • The proposed PE 2 RT score (one point per complication) was associated with the occurrence of major adverse cardiac events on follow-up. • Complications easily detected by cardiac magnetic resonance imaging can help clinicians derive long-term prognostic information on patients with takotsubo syndrome., (© 2023. The Author(s).)

Purpose: The relative ellipsoid zone reflectivity (rEZR) has been proposed as an innovative biomarker for photoreceptor integrity. This study evaluates the rEZR in macular telangiectasia type 2 (MacTel) eyes of different disease stages., Methods: The mean rEZR (ratio ellipsoid zone [EZ]/external limiting membrane [ELM] reflectivity [arbitrary units {AUs}], grey level range = 0-1) was analyzed for an entire spectral domain optical coherence tomography volume scan (global) and for each subfield of the Early Treatment Diabetic Retinopathy Study (ETDRS) grid (topographic) in patients with MacTel and controls. MacTel disease severity was classified according to Gass and Blodi., Results: Linear mixed-model analysis of 145 eyes of 74 patients and 50 eyes of 25 controls revealed globally lower, yet not statistically significant, rEZR values in MacTel eyes. Topographically, most pronounced decreases were found in stages 3 and 4/5 for the temporal inner (coefficient estimates [CEs] = -25.4 [-38.2; -12.6] and -34.1 [-48.7; -19.6] AU, both: P < 0.001), the inferior inner (-29.9 [-44.6; -15.6] and -35.3 [-52.1; -18.5] AU, both: P < 0.001), the nasal inner (-21.5 [-35.52; -7.4] and -31.6 [-47.6; -15.6] AU, P = 0,003 and P < 0.001), and in the superior inner subfield of stage 4/5 (-25.0 [-42.0; -7.9] AU, P = 0.004)., Conclusions: The rEZR showed association with disease severity and the predilection area of MacTel. Given the current understanding of the pathophysiological concept of MacTel, these findings underscore the value of the rEZR as a potential novel biomarker for outer retinal integrity. Longitudinal studies are demanded to better characterize its value as a biomarker for early photoreceptor alterations and disease progression in MacTel.

Background and Objectives : Early postoperative mobilization is central for postoperative outcomes after lower extremity joint replacement surgery. By providing adequate pain control, regional anaesthesia plays an important role for postoperative mobilization. It was the objective of this study to investigate the use of the nociception level index (NOL) to determine the effect of regional anaesthesia in hip or knee arthroplasty patients undergoing general anaesthesia with additional peripheral nerve block. Materials and Methods : Patients received general anaesthesia, and continuous NOL monitoring was established before anaesthesia induction. Depending on the type of surgery, regional anaesthesia was performed with a Fascia Iliaca Block or an Adductor Canal Block. Results : For the final analysis, 35 patients remained, 18 with hip and 17 with knee arthroplasty. We found no significant difference in postoperative pain between hip or knee arthroplasty groups. NOL increase at the time of skin incision was the only parameter associated with postoperative pain measured using a numerical rating scale (NRS > 3) after 24 h in movement (-12.3 vs. +119%, p = 0.005). There was no association with intraoperative NOL values and postoperative opioid consumption, nor was there an association between secondary parameters (bispectral index, heart rate) and postoperative pain levels. Conclusions : Intraoperative NOL changes may indicate regional anaesthesia effectiveness and could be associated with postoperative pain levels. This remains to be confirmed in a larger study.

Background: Cerebral venous sinus thrombosis (CVST) is a known complication of posterior fossa surgery near the sigmoid and transverse sinus. The incidence and treatment of postoperative asymptomatic CVST are controversial., Objective: To analyze incidence, risk factors, and management of asymptomatic postoperative CVST after posterior fossa tumor surgery., Methods: In this retrospective, single-center study, we included all patients who underwent posterior fossa tumor surgery in the semisitting position between January 2013 and December 2020. All patients underwent preoperative and postoperative imaging using MRI with/without additional computed tomography angiography. We analyzed the effect of demographic and surgical data on the incidence of postoperative CVST. Furthermore, therapeutic anticoagulation or conservative treatment for postoperative CVST and the incidence of intracranial hemorrhage were investigated., Results: In total, 266 patients were included. Thirty-three of 266 (12.4%) patients developed postoperative CVST. All patients were asymptomatic. Thirteen of 33 patients received therapeutic anticoagulation, and 20 patients did not. Univariate analysis showed that age ( P = .56), sex ( P = .20), American Society of Anesthesiology status ( P = .13), body mass index ( P = .60), and length of surgery ( P = .176) were not statistically correlated with postoperative CVST. Multivariate analysis revealed that meningioma ( P < .001, odds ratio 11.3, CI 95% 4.1-31.2) and vestibular schwannoma ( P = .013, odds ratio 4.4, CI 95% 1.3-16.3) are risk factors for the development of new postoperative CVST. The use of therapeutic anticoagulation to treat postoperative CVST was associated with a higher rate of intracranial hemorrhage (n = 4, P = .017)., Conclusion: Tumor entity influences the incidence of postoperative CVST. In clinically asymptomatic patients, careful decision making is necessary whether to initiate therapeutic anticoagulation or not., (Copyright © Congress of Neurological Surgeons 2023. All rights reserved.)

Background: Interstitial lung diseases (ILD) are a heterogenous group of diseases, which have pulmonary fibrosis, restrictive lung disease, and decreased diffusion capacity as a common final path. Premature death frequently results not from ILD itself but from comorbidities. Peripheral artery disease (PAD) is a common comorbid disease in different chronic lung diseases. The focus of the present study is to clarify the prevalence of PAD in ILD. Patients and methods: A total of 97 patients with ILD and 30 controls were included in the study. Patients with ILD were subdivided into two groups according to the progression of pulmonary fibrosis: progressive fibrosing and non-progressive fibrosing ILD (PF-ILD and nPF-ILD, respectively). All participants underwent standard angiological and pneumological diagnostic procedures including six-minute walking test, measurement of ankle-brachial-index, and colour-coded duplex sonography. Results: We observed no relevant differences in the baseline characteristics except age. Both, PF-ILD and nPF-ILD patients, presented with a highly increased incidence of atherosclerotic lesions compared to the control group ( p <0.001). PAD was present in all patients with PF-ILD and in 73% of patients with nPF-ILD. These results were confirmed by age-adjusted regression analyses. Conclusions: The present results indicate that ILD is an independent risk factor for atherosclerosis. Patients with PF-ILD are more severely affected than nPF-ILD patients with age as a confounding variable. Atherogenesis in ILD may be mediated by increased cardiovascular risk, systemic inflammation and chronic hypoxemia.

Metabolomics-derived metabolites (henceforth metabolites) may mediate the relationship between modifiable risk factors and clinical biomarkers of metabolic health (henceforth clinical biomarkers). We set out to study the associations of metabolites with clinical biomarkers and a potential mediation effect in a population of young adults. First, we conducted a systematic literature review searching for metabolites associated with 11 clinical biomarkers (inflammation markers, glucose, blood pressure or blood lipids). Second, we replicated the identified associations in a study population of n = 218 (88 males and 130 females, average age of 18 years) participants of the DONALD Study. Sex-stratified linear regression models adjusted for age and BMI and corrected for multiple testing were calculated. Third, we investigated our previously reported metabolites associated with anthropometric and dietary factors mediators in sex-stratified causal mediation analysis. For all steps, both urine and blood metabolites were considered. We found 41 metabolites in the literature associated with clinical biomarkers meeting our inclusion criteria. We were able to replicate an inverse association of betaine with CRP in women, between body mass index and C-reactive protein (CRP) and between body fat and leptin. There was no evidence of mediation by lifestyle-related metabolites after correction for multiple testing. We were only able to partially replicate previous findings in our age group and did not find evidence of mediation. The complex interactions between lifestyle factors, the metabolome, and clinical biomarkers warrant further investigation., (© 2023. The Author(s).)

Purpose: Research suggests that diet influences cognitive function and the risk for neurodegenerative disease. The present study aimed to determine whether a recently developed diet score, based on recommendations for dietary priorities for cardio metabolic health, was associated with fluid intelligence, and whether these associations were modified by individual genetic disposition., Methods: This research has been conducted using the UK Biobank Resource. Analyses were performed using self-report data on diet and the results for the verbal-numerical reasoning test of fluid intelligence of 104,895 individuals (46% male: mean age at recruitment 57.1 years (range 40-70)). For each participant, a diet score and a polygenic score (PGS) were constructed, which evaluated predefined cut-offs for the intake of fruit, vegetables, fish, processed meat, unprocessed meat, whole grain, and refined grain, and ranged from 0 (unfavorable) to 7 (favorable). To investigate whether the diet score was associated with fluid intelligence, and whether the association was modified by PGS, linear regression analyses were performed., Results: The average diet score was 3.9 (SD 1.4). After adjustment for selected confounders, a positive association was found between baseline fluid intelligence and PGS (P < 0.001). No association was found between baseline fluid intelligence and diet score (P = 0.601), even after stratification for PGS, or in participants with longitudinal data available (n = 9,482)., Conclusion: In this middle-aged cohort, no evidence was found for an association between the investigated diet score and either baseline or longitudinal fluid intelligence. However, as in previous reports, fluid intelligence was strongly associated with a PGS for general cognitive function., (© 2022. The Author(s).)

Background. Vitamins A, D and E and beta-carotene may have a protective function for cognitive health, due to their antioxidant capacities. Methods. We analyzed data from 1334 non-demented participants (mean age 84 years) from the AgeCoDe study, a prospective multicenter-cohort of elderly general-practitioner patients in Germany, of whom n = 250 developed all-cause dementia and n = 209 developed Alzheimer’s dementia (AD) during 7 years of follow-up. We examined whether concentrations of vitamins A (retinol), D (25-hydroxycholecalciferol) and E (alpha-tocopherol) and beta-carotene, would be associated with incident (AD) dementia. Results. In our sample, 33.7% had optimum vitamin D concentrations (≥50 nmol/L). Higher concentrations of vitamin D were associated with lower incidence of all-cause dementia and AD (HR 0.99 (95%CI 0.98; 0.99); HR0.99 (95%CI 0.98; 0.99), respectively). In particular, subjects with vitamin D deficiency (25.3%, <25 nmol/L) were at increased risk for all-cause dementia and AD (HR1.91 (95%CI 1.30; 2.81); HR2.28 (95%CI 1.47; 3.53), respectively). Vitamins A and E and beta-carotene were unrelated to (AD) dementia. Conclusions. Vitamin D deficiency increased the risk to develop (AD) dementia. Our study supports the advice for monitoring vitamin D status in the elderly and vitamin D supplementation in those with vitamin D deficiency. We observed no relationships between the other vitamins with incident (AD) dementia, which is in line with previous observational studies.

Non-syndromic cleft lip with/without cleft palate (nsCL/P) is a highly heritable facial disorder. To date, systematic investigations of the contribution of rare variants in non-coding regions to nsCL/P etiology are sparse. Here, we re-analyzed available whole-genome sequence (WGS) data from 211 European case-parent trios with nsCL/P and identified 13,522 de novo mutations (DNMs) in nsCL/P cases, 13,055 of which mapped to non-coding regions. We integrated these data with DNMs from a reference cohort, with results of previous genome-wide association studies (GWASs), and functional and epigenetic datasets of relevance to embryonic facial development. A significant enrichment of nsCL/P DNMs was observed at two GWAS risk loci (4q28.1 (p = 8 × 10 -4 ) and 2p21 (p = 0.02)), suggesting a convergence of both common and rare variants at these loci. We also mapped the DNMs to 810 position weight matrices indicative of transcription factor (TF) binding, and quantified the effect of the allelic changes in silico . This revealed a nominally significant overrepresentation of DNMs (p = 0.037), and a stronger effect on binding strength, for DNMs located in the sequence of the core binding region of the TF Musculin (MSC). Notably, MSC is involved in facial muscle development, together with a set of nsCL/P genes located at GWAS loci. Supported by additional results from single-cell transcriptomic data and molecular binding assays, this suggests that variation in MSC binding sites contributes to nsCL/P etiology. Our study describes a set of approaches that can be applied to increase the added value of WGS data., Competing Interests: The authors declare no competing interests., (© 2022 The Authors.)

We sought to assess the anti-seizure efficacy of carbamazepine (CBZ) and retention rate (RR) in randomized, controlled trials (RCTs) in epilepsy. Our analysis was carried out according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Inclusion criteria were monotherapy of CBZ in adequate dosage for epilepsy treatment and RCT duration of ≥3 months. Outcome measures were seizure freedom rate (SFR) and RR. Random-effects meta-analyses were performed to allow for comparison with other anti-seizure medications (ASMs). Thirty RCTs of 734 were included. SFR at last follow-up ranged from 11% at 36 months to 85% at 3 months. The aggregated SFR at 6 months was 58% (CI 49-66%) and 48% (CI 40-57%) at 12 months. The 6-month SFR among blinded studies was 55% (CI 43-66%), compared with 61% (CI 50-71%) in unblinded studies. The 12-month SFR was not significantly linked to the age of study participants. RR varied from 36% at 24 months to 81% at 6 months. When adjusting for blinding, the aggregated 6-month RR in blinded studies was 59% (CI 52-66%) vs 76% (CI 71-81%) in unblinded studies. The point estimates of SFR of all RCTs showed an upward time trend, with an increase of approximately 15% between the years 1981 and 2018. In conclusion, the SFR and RR of CBZ were highly variable in RCTs and especially affected by study duration and blinding. These results underscore the impact of the design of RCTs investigating ASM and may challenge the wide use of CBZ as a comparator., (© 2022 The Authors. Epilepsia Open published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)

Background: The lymphocyte transformation test (LTT) is an in vitro test system for the detection of a sensitization in the context of allergies to drugs. Its reported sensitivity varies largely and seems to be affected by different parameters. In review articles, the average LTT performance was often calculated by combining overall mean sensitivities of various published studies, but without considering different patient characteristics or varying patient numbers per publication., Objective: To investigate the impact of different patient-specific and methodological parameters on the sensitivity of the LTT based on data on the level of the individual patient extracted from single studies., Methods: We performed an advanced literature search in PubMed and screened the identified publications according to previously defined inclusion criteria. In total, individual patient data from 721 patients were extracted from 30 studies. Random-effects meta-regression analyses were performed., Results: The analysis indicate that the enzyme-linked immunosorbent assay-based read-out is more sensitive compared with the classical radioactivity method (enzyme-linked immunosorbent assay: 80% vs radioactivity: 66%; P = .08). Interestingly, drug reaction with eosinophilia and systemic symptoms/drug-induced hypersensitivity syndrome is associated with a higher probability of a positive LTT test result compared with other investigated clinical phenotypes ("drug reaction with eosinophilia and systemic symptoms/drug-induced hypersensitivity syndrome" vs "bullous reaction"; odds ratio, 2.52; P value = .003). Our analysis also revealed an impact of the time to testing period after the occurrence of the allergic event ("&lt; 2 weeks" vs "2 weeks-2 months"; odds ratio, 2.12; P value = .03)., Conclusion: The read-out method and relevant clinical parameters affect the sensitivity of the LTT. These findings are based on a meta-analysis providing a higher level of evidence than a single study or previous reviews not considering individual patient data., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Scope: Habitual diet may be reflected in metabolite profiles that can improve accurate assessment of dietary exposure and further enhance our understanding of their link to health conditions. The study aims to explore the relationship of habitual food intake with blood and urine metabolites in adolescents and young adults., Methods: The study population comprises 228 participants (94 males and 134 females) of the DONALD study. Dietary intake is assessed by yearly repeated 3d-food records. Habitual diet is estimated as the average consumption of 23 food groups in adolescence. Using an untargeted metabolomics approach, the study quantifies 2638 metabolites in plasma and 1407 metabolites in urine. In each sex, unique diet-metabolite associations using orthogonal projection to latent structures (oPLS) and random forests (RF) is determined., Results: Six metabolites in agreement between oPLS and RF in urine, one in female (vanillylmandelate to processed/other meat) and five in males (indole-3-acetamide, and N6-methyladenosine to eggs; hippurate, citraconate/glutaconate, and X - 12111 to vegetables) are observed. No association in blood in agreement is observed., Conclusion: A limited reflection of habitual food group intake by single metabolites in urine and not in blood is observed. The explored biomarkers should be confirmed in additional studies., (© 2022 The Authors. Molecular Nutrition & Food Research published by Wiley-VCH GmbH.)

Background: CNS germinoma, being marker-negative, are mainly diagnosed by histological examination. These tumors predominantly appear in the suprasellar and/or pineal region. In contrast to the suprasellar region, where biopsy is the standard procedure in case of a suspected germ-cell tumor to avoid mutilation to the endocrine structures, pineal tumors are more accessible to primary resection. We evaluated the perioperative course of patients with pineal germinoma who were diagnosed by primary biopsy or resection in the SIOP CNS GCT 96 trial. Methods: Overall, 235 patients had germinoma, with pineal localization in 113. The relationship between initial symptoms, tumor size, and postoperative complications was analyzed. Results: Of 111 evaluable patients, initial symptoms were headache (n = 98), hydrocephalus (n = 93), double vision (n = 62), Parinaud syndrome (n = 57), and papilledema (n = 44). There was no significant relationship between tumor size and primary symptoms. A total of 57 patients underwent primary resection and 54 underwent biopsy. Postoperative complications were reported in 43.2% of patients after resection and in 11.4% after biopsy (p < 0.008). Biopsy was significantly more commonly performed on larger tumors (p= 0.002). Conclusions: These results support the practice of biopsy over resection for histological confirmation of pineal germinoma.

Purpose: The available questionnaires for quality-of-life (QoL) assessments are age-group specific, limiting comparability and impeding longitudinal analyses. The comparability of measurements, however, is a necessary condition for gaining scientific evidence. To overcome this problem, we assessed the viability of harmonising data from paediatric and adult patient-reported outcome (PRO) measures., Method: To this end, we linked physical functioning scores from the Paediatric Quality of Life Inventory (PedsQL) and the Paediatric Quality of Life Questionnaire (PEDQOL) to the European Organisation for Research and Treatment of Cancer Core Questionnaire (EORTC QLQ-C30) for adults. Samples from the EURAMOS-1 QoL sub-study of 75 (PedsQL) and 112 (PEDQOL) adolescent osteosarcoma patients were concurrently administered both paediatric and adult questionnaires on 98 (PedsQL) and 156 (PEDQOL) occasions. We identified corresponding scores using the single-group equipercentile linking method., Results: Linked physical functioning scores showed sufficient concordance to the EORTC QLQ-C30: Lin's ρ = 0.74 (PedsQL) and Lin's ρ = 0.64 (PEDQOL)., Conclusion: Score linking provides clinicians and researchers with a common metric for assessing QoL with PRO measures across the entire lifespan of patients., Competing Interests: Conflict of interest statement The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: SB reports grants from Deutsche Krebshilfe, Deutsche Forschungsgemeinschaft, and European Science Foundation during the conduct of the study and personal fees from Lilly, Bayer, Pfizer, Novartis, Isofol, Clinigen, Sensorion, Ipsen, and Roche outside the submitted work. MRS reports grants and nonfinancial support from Astellas, grants from Clovis, grants and nonfinancial support from Janssen, grants and nonfinancial support from Novartis, grants and nonfinancial support from Pfizer, and grants and nonfinancial support from Sanofi, during the conduct of the study and personal fees from Lilly Oncology and personal fees from Janssen for educational courses and workshops outside the submitted work. NM reports employment by Five Prime Therapeutics, Inc and Sanofi US, outside the submitted work. The remaining authors declare no conflicts of interest., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: The validity of current tools for intraoperative objective assessment of nociception/antinociception balance during anesthesia in young and very young surgery children is unknown., Aim: Primary aim of the study was to test the hypothesis that the Newborn Infant Parasympathetic Evaluation (NIPE) index performs better in indicating nociception in anesthetized children below 2 years than changes in heart rate. Secondary aims were to evaluate associations between intraoperative changes in NIPE index values and postoperative pain and emergence delirium., Methods: Fifty-one children aged <2 years who underwent surgery were included in this prospective observational study. Patients were assigned to either group 1 (healthy children, n = 31) or group 2 (critically ill, ventilated premature infants and neonates, n = 20). The NIPE index and heart rate in response to three defined nociceptive stimuli were continuously recorded. Two different scales, Kindliche Unbehagens- und Schmerzskala (KUS) and Pediatric Anesthesia Emergence Delirium (PAED) as well as a Pain Questionnaire were used to assess postoperative pain levels and emergence delirium., Results: In total, 110 nociceptive events were evaluated. The analysis revealed a statistically significant association between a decrease in the NIPE index and all nociceptive stimuli, with a sensitivity of 92% and a specificity of 96%. The mean percentage decrease ranged from approx. 15%-30% and was highly statistically significant in both groups and for each of the nociceptive events except for venous puncture (p = .004). In contrast, no consistent change in heart rate was demonstrated. The KUS and PAED scale scores were significantly associated with the duration of anesthesia (p = .04), but not with intraoperative NIPE depression., Conclusion: The NIPE index was reliable for assessing intraoperative nociception in children aged <2 years and was more reproducible for detecting specific nociceptive stimuli during general anesthesia than heart rate. An effect on postoperative outcome is still elusive., (© 2022 The Authors. Pediatric Anesthesia published by John Wiley & Sons Ltd.)

The influence of perioperative red blood cell (RBC) transfusion on prognosis of glioblastoma patients continues to be inconclusive. The aim of the present study was to evaluate the association between perioperative blood transfusion (PBT) and overall survival (OS) in patients with newly diagnosed glioblastoma. Between 2013 and 2018, 240 patients with newly diagnosed glioblastoma underwent surgical resection of intracerebral mass lesion at the authors' institution. PBT was defined as the transfusion of RBC within 5 days from the day of surgery. The impact of PBT on overall survival was assessed using Kaplan-Meier analysis and multivariate regression analysis. Seventeen out of 240 patients (7%) with newly diagnosed glioblastoma received PBT. The overall median number of blood units transfused was 2 (95% CI 1-6). Patients who received PBT achieved a poorer median OS compared to patients without PBT (7 versus 18 months; p < 0.0001). Multivariate analysis identified "age > 65 years" (p < 0.0001, OR 6.4, 95% CI 3.3-12.3), "STR" (p = 0.001, OR 3.2, 95% CI 1.6-6.1), "unmethylated MGMT status" (p < 0.001, OR 3.3, 95% CI 1.7-6.4), and "perioperative RBC transfusion" (p = 0.01, OR 6.0, 95% CI 1.5-23.4) as significantly and independently associated with 1-year mortality. Perioperative RBC transfusion compromises survival in patients with glioblastoma indicating the need to minimize the use of transfusions at the time of surgery. Obeying evidence-based transfusion guidelines provides an opportunity to reduce transfusion rates in this population with a potentially positive effect on survival., (© 2021. The Author(s).)

We present a new procedure for enhanced variable selection for component-wise gradient boosting. Statistical boosting is a computational approach that emerged from machine learning, which allows to fit regression models in the presence of high-dimensional data. Furthermore, the algorithm can lead to data-driven variable selection. In practice, however, the final models typically tend to include too many variables in some situations. This occurs particularly for low-dimensional data ( p < n ), where we observe a slow overfitting behavior of boosting. As a result, more variables get included into the final model without altering the prediction accuracy. Many of these false positives are incorporated with a small coefficient and therefore have a small impact, but lead to a larger model. We try to overcome this issue by giving the algorithm the chance to deselect base-learners with minor importance. We analyze the impact of the new approach on variable selection and prediction performance in comparison to alternative methods including boosting with earlier stopping as well as twin boosting. We illustrate our approach with data of an ongoing cohort study for chronic kidney disease patients, where the most influential predictors for the health-related quality of life measure are selected in a distributional regression approach based on beta regression.

Background and Aims: We hypothesized that in long-term immobilized intensive care unit (ICU) patients, both the quantity and quality of protein nutrition are vital in supporting muscle mass maintenance. Hence, the aim of this secondary analysis of our recently performed RCT was to calculate the intake of individual amino acids and to evaluate the potential associations of amino acid patterns with muscle mass loss during the ICU stay., Methods: Clinical and nutritional data were collected from a recent RCT conducted in long-term immobilized, critically ill patients receiving medical nutrition therapy with either 1.8 g (interventional group) or 1.2 g (standard group) of protein/amino acids per kg body weight per day over 4 weeks. Intake of the individual amino acids as well as the sum scores of the indispensable, conditionally indispensable, and dispensable amino acids were calculated for all patients, both group specific (n = 21 in each group) and in total (n = 42), based on the detailed nutrition protocols; inter-group differences were analyzed by t-tests. Linear regression models were used to test the effects of individual amino acids and the sum scores on the extent of skeletal muscle loss by measuring the quadriceps muscle layer thickness during the study period. The significance level was adjusted for multiple testing according to the Bonferroni procedure (α = 0.002)., Results: In both groups, the proportion of indispensable amino acids was approximately 41% of the total exogenous protein supply, with the proportion of enteral administration slightly over 50%. The intake of conditionally indispensable amino acids (glutamine, tyrosine, cysteine, histidine, and arginine) accounted for 17% and 18% of the total amino acids in the interventional and standard groups, respectively; glutamine (5% of total amino acids) was exclusively administered enterally. The intake of dispensable amino acid varied widely, with glutamic acid, proline, and asparagine/aspartic acid representing the highest proportions (10%, 8%, and 8% of total amino acids, respectively). For all amino acids, no statistically significant association was observed between the quantitative intake and the skeletal muscle changes after terminating the intervention phase., Conclusion: This secondary analysis of the RCT conducted in routine clinical practice did not support our working hypothesis that the amino acid patterns of medical nutrition therapy have a statistically significant impact on the skeletal muscle loss in long-term immobilized ICU patients. Due to the limited variety of enteral/parenteral products used in this single-center study, the calculated amino acid patterns showed only small differences. Larger multi-center trials with adequate power are needed to evaluate the potential effects of the individual amino acids or defined amino acid patterns on the muscle protein metabolism in further detail., Trial Registration: German Clinical Trials Register (http://www.drks.de); DRKS-ID: DRKS00013594., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest., (Copyright © 2021 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.)

Purpose: We aimed to validate myfood24-Germany, a web-based 24-h dietary recall (24HDR), by comparing its performance with a weighed dietary record (WDR) and biomarkers., Methods: 97 adults (77% female) completed a 3-day WDR with a 24-h urine collection on day 3, followed by at least one 24HDR with myfood24-Germany (corresponding to day 3 of the WDR). Intake of energy and 32 nutrients assessed by myfood24-Germany and the WDR for the same day were compared (method comparison). Intakes of protein and potassium assessed by myfood24-Germany/WDR were compared with intake estimated from urinary biomarkers for protein and potassium (biomarker comparison)., Results: In the method comparison, significant correlations were found for energy and all tested nutrients (range 0.45-0.87). There was no significant difference between both methods in the assessed mean energy and macronutrient intake. However, myfood24-Germany underestimated mean intake of 15 nutrients. In the biomarker comparison, protein intake reported by myfood24-Germany/WDR was on average 10%/8% lower than estimated by biomarker. There was no significant difference in mean potassium intake assessed by myfood24-Germany/WDR and biomarker. However, a shared bias in the assessment of potassium intake was observed for both instruments. Concordance correlation coefficients (p c ) and weighted Kappa coefficients (κ) confirmed good agreement with the biomarker estimates for myfood24-Germany/WDR in case of protein (p c  = 0.58/0.66, κ = 0.51/0.53) and moderate agreement in case of potassium (p c  = 0.44/0.51; κ = 0.30/0.33)., Conclusion: Our results suggest that myfood24-Germany is of comparable validity to traditional dietary assessment methods., (© 2021. The Author(s).)

Alterations in frontal and parietal neural activations during working memory task performance have been suggested as a candidate endophenotype of obsessive-compulsive disorder (OCD) in studies involving first-degree relatives. However, the direct link between genetic risk for OCD and neuro-functional alterations during working memory performance has not been investigated to date. Thus, the aim of the current functional magnetic resonance imaging (fMRI) study was to test the direct association between polygenic risk for OCD and neural activity during the performance of a numeric n-back task with four working memory load conditions in 128 participants, including patients with OCD, unaffected first-degree relatives of OCD patients, and healthy controls. Behavioral results show a significant performance deficit at high working memory load in both patients with OCD and first-degree relatives (p < 0.05). A whole-brain analysis of the fMRI data indicated decreased neural activity in bilateral inferior parietal lobule and dorsolateral prefrontal cortex in both patients and relatives. Most importantly, OCD polygenic risk scores predicted neural activity in orbitofrontal cortex. Results indicate that genetic risk for OCD can partly explain alterations in brain response during working memory performance, supporting the notion of a neuro-functional endophenotype for OCD., (© 2021. The Author(s).)

Background: Head and neck cancer (HNC) patients are particularly vulnerable to drug-related problems (DRPs) given the toxicity of concomitant chemoradiotherapy (CCRT)., Objective: To investigate the number and type of potential DRPs (pDRPs) in HNC outpatients undergoing five consecutive cycles of CCRT., Methods: A single-centre, non-randomized, non-interventional, observational study was conducted at the Oncological Outpatient Clinic of the Center for Integrated Oncology at the University Hospital Bonn, Germany. Clinical pharmacists took a comprehensive medication history, documented laboratory data, assessed patients' symptom burden, and retrospectively performed medication reviews at study entry and on the first day of each therapy cycle without any clinical intervention., Results: In 26 patients, the mean number of pDRPs continuously increased during therapy course, from 4.8 (SD 2.7, range 2-12) at cycle 1 to 6.9 (SD 2.6, range 2-12) at cycle 5, with drug-drug interactions, adverse drug reactions, inappropriate durations of use, and inappropriate dosage intervals being the most common. Considering only new and recurrent pDRPs, the mean number was 4.3 (SD 2.3, range 2-9) at cycle 1 and lower in the further therapy course with an average of 1.3 (SD 1.7, range 0-7) at cycle 2 and 1.9 (SD 1.5, range 0-5) at cycle 5. The number of pDRPs was found to be associated with medication regimen complexity and health-related quality of life assessed in the first therapy cycle., Conclusion: pDRPs frequently occurred in HNC outpatients demonstrating the need for pharmaceutical care. A methodological framework for repeated medication reviews was established, facilitating implementation into routine healthcare practice.

Background: To prospectively analyze factors associated with detecting epileptogenic lesions on MRI within the work-sharing process of neurologists, epileptologists, radiologists and neuroradiologists., Methods: We assembled four sets of six MRI scans, each set representing five typical epileptogenic lesions (hippocampal sclerosis or limbic encephalitis; focal cortical dysplasias; periventricular nodular or other heterotopias; long-term epilepsy associated tumors; gliotic scar, hemosiderin or cavernoma), and non - lesional epilepsy. At professional conferences, we invited neurologists, epileptologists, radiologists, and neuroradiologists to read two out of four MRI sets, one of which was presented with a clinical focus hypothesis. Participants were randomly assigned to MRI sets. Effects of examiners' specialty, duration of training and professional experience on detection rate of epileptogenic lesions were investigated., Results: Fourty-eight neurologists, 22 epileptologists, 20 radiologists and 21 neuroradiologists read 1323 MRI scans. Overall, 613 of 1101 (55.7%) epileptogenic lesions were detected. Long-term epilepsy associated tumors (182/221, 82.4%) were found more frequently than gliotic scar, hemosiderin or cavernoma (157/220, 71.4%), hippocampal sclerosis or limbic encephalitis (141/220, 64.1%), nodular heterotopia (68/220, 30.9%) and focal cortical dysplasias (65/220, 29.5%, p < 0.001). Provision of a focus hypothesis improved the detection of hippocampal sclerosis or limbic encephalitis (86/110, 78.2% vs 55/110, 50%, p < 0.001) and focal cortical dysplasias (40/110, 36.4% vs 25/110, 22.7%, p = 0.037). Neuroradiologists and epileptologists were more likely than radiologists and neurologists to be amongst the most successful readers. In multivariable analysis, type of epileptogenic lesion, specialty of MRI reader, and provision of focus hypothesis predicted correct identification of epileptogenic lesions., Conclusions: Epileptogenic lesions are often not recognized on MRI even by expert readers. Their detection can be improved by providing a focus hypothesis. These results stress the need for training in the MRI characteristics of epilepsy - specific pathology, and, most importantly, interdisciplinary communication between neurologists/epileptologists and (neuro)radiologists to improve detection of epileptogenic lesions., (© 2021. The Author(s).)

Background: Oro-facial dysfunctions (OFDs; oro-facial myofunctional disorders) in children and childhood apraxia of speech (CAS) often cause severe problems in articulation, chewing, swallowing and oral posture., Objectives: Pathognomonic symptoms could yet not be identified, but central problems in planning, programming, timing and automating oro-facial, as well as other fine motor skills, are assumed to be affected., Methods: To investigate the nature of motor and coordinative deficits in OFD and CAS, digitomotography was applied. The testing focused on recording frequency, force, rhythm and regularity of the index finger including speeded and metronome tapping tasks. 25 children with OFD (7 girls and 18 boys, age 7.9 ± 2.3) and 5 children with CAS (0 girls and 5 boys, age 7.6 ± 2.3), and 31 healthy controls (12 girls and 19 boys, age 9.3 ± 2.2) were tested. Statistical significance was accepted at α = 0.05. ANOVA test, non-parametric Mann-Whitney U test, Kruskal-Wallis test and Spearman's rank correlation coefficient were used., Results: Cross-sectional data revealed consistent significant differences between children with OFD and healthy controls concerning frequency, force, rhythm and regularity of index finger tapping. Individuals with CAS showed particularly low results. Tapping results correlated with disease burden., Conclusion: These findings support that underlying superordinated sensorimotor deficits exist. This may help phenotyping and influence diagnostical and therapeutical approaches., (©2021 The Authors. Journal of Oral Rehabilitation published by John Wiley & Sons Ltd.)

Genetic discoveries of Alzheimer's disease are the drivers of our understanding, and together with polygenetic risk stratification can contribute towards planning of feasible and efficient preventive and curative clinical trials. We first perform a large genetic association study by merging all available case-control datasets and by-proxy study results (discovery n = 409,435 and validation size n = 58,190). Here, we add six variants associated with Alzheimer's disease risk (near APP, CHRNE, PRKD3/NDUFAF7, PLCG2 and two exonic variants in the SHARPIN gene). Assessment of the polygenic risk score and stratifying by APOE reveal a 4 to 5.5 years difference in median age at onset of Alzheimer's disease patients in APOE ɛ4 carriers. Because of this study, the underlying mechanisms of APP can be studied to refine the amyloid cascade and the polygenic risk score provides a tool to select individuals at high risk of Alzheimer's disease.

Fear and exploration are crucial traits determining how animals behave in novel situations, and thus, they influence animal welfare. The aim of this study was the characterization of these behavioral traits among different strains to identify interesting alternatives for future poultry production. Whereas the Novel Object Test (NOT) focuses on fear and exploration of novel objects, the Avoidance Distance Test (ADT) addresses this in the context of humans. Here, a commercial hybrid line, a dual-purpose hybrid and a local adapted strain were tested. For the differences between strains and development of fear, Lohmann Brown ( n = 714), Lohmann Dual ( n = 844) and Rhinelander ( n = 458) were observed weekly until maturity. Results show that fear and exploration towards unknown objects and humans are breed-specific (all p < 0.01). Additionally, development of fear in NOT and ADT differed between all three strains (both p < 0.01). The expressions of fear of humans or objects should be regarded as characteristics adapted for different husbandry systems and breeding goals, e.g., high exploratory behavior in aviary or high avoidance of predators in free-ranging husbandry or at least a balanced ratio between fear and exploration. Characterization of behavioral traits among different strains, understanding diversity and integrating these behaviors into future breeding and husbandry systems might reflect the need to preserve local strains and the potential to improve animal welfare.

Background: Omega-3 (n-3) and omega-6 (n-6) polyunsaturated fatty acids (PUFAs) may have different effects on cognitive health due to their anti- or pro-inflammatory properties., Methods: We aimed to prospectively examine the relationships between n-3 and n-6 PUFA contents in serum phospholipids with incident all-cause dementia and Alzheimer's disease dementia (AD). We included 1264 non-demented participants aged 84 ± 3 years from the German Study on Ageing, Cognition, and Dementia in Primary Care Patients (AgeCoDe) multicenter-cohort study. We investigated whether fatty acid concentrations in serum phospholipids, especially eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), alpha-linolenic acid (ALA), linoleic acid (LA), dihomo-γ-linolenic acid (DGLA), and arachidonic acid (AA), were associated with risk of incident all-cause dementia and AD., Results: During the follow-up window of seven years, 233 participants developed dementia. Higher concentrations of EPA were associated with a lower incidence of AD (hazard ratio (HR) 0.76 (95% CI 0.63; 0.93)). We also observed that higher concentrations of EPA were associated with a decreased risk for all-cause dementia (HR 0.76 (95% CI 0.61; 0.94)) and AD (HR 0.66 (95% CI 0.51; 0.85)) among apolipoprotein E ε4 (APOE ε4) non-carriers but not among APOE ε4 carriers. No other fatty acids were significantly associated with AD or dementia., Conclusions: Higher concentrations of EPA were associated with a lower risk of incident AD. This further supports a beneficial role of n-3 PUFAs for cognitive health in old age.

Indication for surgical treatment in patients with intracranial meningioma must include both clinical aspects and an individual risk-benefit stratification, especially in geriatric patients. Prolonged mechanical ventilation (PMV) has not been investigated for its potential effects in patients with meningioma. We therefore analyzed the impact of PMV on mortality in geriatric patients who had undergone meningioma resection. Between 2009 and 2019, 261 patients aged ≥ 70 years were surgically treated for intracranial meningioma at our institution. PMV was defined as postoperative invasive ventilation of >7 days. Postoperative PMV was present in 17 of 261 geriatric meningioma patients (7%). Twenty-five geriatric patients (10%) died within 1 year after surgery. A scoring system ("ACKT") based on the variables of age, preoperative C-reactive protein (CRP) value, Karnofsky performance scale and tumor size supports prediction of postoperative PMV (sensitivity 73%, specificity 84%). PMV is significantly associated with increased mortality after surgical treatment of meningiomas in geriatric patients. Furthermore, we suggest a novel score ("ACKT") to preoperatively estimate the risk of PMV occurrence, which might help to guide future risk-benefit assessment and patient counseling in the geriatric meningioma population.

Purpose:  To evaluate the longitudinal pattern of fetal heart rate short term variation (STV) and Doppler indices and their correlation to each other in severe growth restricted (IUGR) fetuses., Materials and Methods:  In this retrospective study, pregnancies with a birth weight below the 10th percentile, born between 24 and 34 gestational weeks with serial Doppler measurements in combination with a computerized CTG (cCTG) with calculated STV were included. Longitudinal changes of both Doppler indices and STV values were evaluated with generalized additive models, adjusted for gestational age and the individual. For all measurements the frequency of abnormal values with regard to the time interval before delivery and Pearson correlations between Doppler indices and STV values were calculated., Results:  41 fetuses with a total of 1413 observations were included. Over the course of the whole study period, regression analyses showed no significant change of STV values (p = 0.38). Only on the day of delivery, a prominent decrease was observed (mean STV d28-22: 7.97 vs. mean STV on day 0: 6.8). Doppler indices of UA and MCA showed a continuous, significant deterioration starting about three weeks prior to delivery (p = 0.007; UA and p < 0.001, MCA). Correlation between any Doppler index and STV values was poor., Conclusion:  Fetal heart rate STV does not deteriorate continuously. Therefore, cCTG monitoring should be performed at least daily in these high-risk fetuses. Doppler indices of umbilical artery (UA) and middle cerebral artery (MCA), however, showed continuous deterioration starting about 3 weeks prior to delivery., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)