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Association of interleukin-6 serum levels with local tumor stage and lymph node metastasis of urothelial carcinoma
No full textIntroduction
Elevated preoperative interleukin-6 (IL-6) blood levels in urothelial carcinoma (UC) patients undergoing radical cystectomy (RC) have been linked to adverse pathological features. The aim of this prospective study of patients undergoing RC was to analyze whether preoperative IL-6 serum levels (i) correlate with local tumor stage, (ii) are associated with lymph node metastasis, and (iii) are elevated in patients with other oncologic or nononcologic indications for RC.
Materials and Methods
Patients undergoing RC for oncologic or nononcologic indications were prospectively included. IL-6 serum levels were measured preoperatively. Statistical analysis included Spearman correlation analysis and Receiver Operating Characteristics (ROC) analysis. ClinicalTrials.gov: NCT05153694.
Results
Between December 2021 and November 2024, 214 patients underwent RC at our department. Preoperative IL-6 serum levels were measured in 169 patients who provided informed consent. In UC patients, IL-6 levels correlated with local tumor stage (r = 0.30, P = 0.001) and higher levels were associated with lymph node metastasis (P = 0.001). The AUC was 0.678 (95% CI 0.58–0.77) and 0.681 (95% CI 0.58–0.79) for non-organ confined tumor growth and lymph node metastasis, respectively. No significant difference in preoperative IL-6 serum levels was observed between UC patients and patients with other oncologic or nononcologic indications for RC.
Conclusion
This prospective study found that elevated preoperative IL-6 serum levels correlated with local tumor stage and were associated with lymph node metastasis in UC patients undergoing RC. However, IL-6 levels were also elevated in patients with other oncologic or nononcologic indications for RC, underscoring the need for careful interpretation of this marker
Turning Straw into Gold : Constantin von Tischendorf's Jewish Manuscript Collections
No full textThis study outlines Constantin von Tischendorf's lesser-known activities as a collector of Rabbanite and Qaraite books. Tischendorf amassed these items on two of his journeys to the eastern Mediterranean. They relate to his overall scholarly activities in significant ways, since their sale to the Imperial Public Library in Saint Petersburg gave him an opportunity to enter into conversation with Russian officials, who went on to fund his third journey, from which he brought a part of Codex Sinaiticus to Russia. His attitude towards Jewish sources was largely utilitarian: he thought of them as tools to better interpret the New Testament
PROM at term: when might be the best time to induce labour? A retrospective analysis
No full textPurpose: PROM after 37 weeks of gestation occurs in approximately 10% of pregnancies. When spontaneous onset of labour does not follow, induction is recommended to decrease the risk of infection for both mother and child. However, there is no clear consensus on whether induction before 24 h after PROM results in fewer complications compared to induction after > 24 h.
Material and methods: This retrospective observational study analysed the outcomes of 3174 women with PROM admitted to the delivery room of LMU Women's Hospital between 10/2015 and 09/2020. We evaluated whether timing of labour induction was associated with maternal or newborn postpartum infection rates.
Results: Comparing women with spontaneous onset of labour to those who underwent induction, no significant differences were found in maternal CRP or leukocyte levels, fever, endometritis, or Group B streptococcus colonization. However, intrapartum antibiotic therapy was significantly higher in the induction group. When the induction group was subdivided based on the interval from PROM to induction, no significant differences were observed in maternal infection parameters, need for antibiotics, postpartum length of hospital stay, or endometritis. For newborn infections, a significant difference in CRP levels was found, with higher levels in the groups with "induction 24 h".
Conclusion: The presented data suggests that waiting for spontaneous contractions within the first 24 h after PROM was not associated with the risk of infection if no initial signs for infection are present. However, beyond 24 h, the risk of infection increased. These findings support current recommendations regarding the timing of induction after PROM
Chemotherapy-free combination of ibrutinib and obinutuzumab for untreated advanced follicular lymphoma: results of a phase II study from the German Lymphoma Alliance
No full textImmunochemotherapy induces long-term responses in patients with follicular lymphoma. However, the toxicity of chemotherapy remains a relevant challenge. The Bruton tyrosine kinase inhibitor ibrutinib has shown significant activity in patients with indolent B-cell lymphoma. Combining ibrutinib with obinutuzumab may, therefore, be an attractive chemotherapy-free option. We conducted a prospective, single-arm, multicenter phase II trial to evaluate the chemotherapy-free regimen of obinutuzumab plus ibrutinib in patients with previously untreated advanced-stage follicular lymphoma. Patients received six 21-day cycles of ibrutinib and obinutuzumab for induction and 12 additional 2-month cycles for maintenance. The primary endpoint was 1-year progression-free survival (PFS). The study was powered to detect an improvement of 10% over the 1-year PFS of 85%. Ninety-eight patients were enrolled in the trial. The median follow-up was 5.5 years. After induction, five patients (5%) had a complete response and 82 (85%) had a partial response. The 1-year PFS was 80%, missing the prospected improvement of a 1-year PFS of 85% (P=0.93). The median PFS was 4.5 years; median duration of response and overall survival were not reached. The most common adverse events of grade 3/4 were neutropenia, lung infection, hypertension, fatigue, rash and thrombocytopenia. The trial of a chemotherapy-free regimen of obinutuzumab and ibrutinib in follicular lymphoma patients failed to demonstrate a 10% improvement in the primary efficacy endpoint. However, the combination produced durable and deep responses and had an acceptable safety profile. Trial registration, EudraCT-Number: 2014-005164-15
Dyspnea after a first episode of pulmonary embolism: prevalence, predictors and long-term associations with health-related quality of life
Get PDFIntroduction: The predictors and consequences of dyspnea after pulmonary embolism (PE) are only rarely investigated. The present study aimed to characterize dyspnea and its associated factors in patients with incident PE up to 2 years after hospital discharge.
Methods: Data from the German "Lungenembolie Augsburg (LEA)" cohort study were used. Baseline characteristics of adult patients with a first episode of acute PE were collected during hospital stay. Participants completed postal questionnaires 3, 6, 12, and 24 months after their PE. Dyspnea was assessed using the Chronic Respiratory Questionnaire (CRQ) and the Pulmonary Embolism Quality of Life Questionnaire (PEmb-QoL) was used to measure health-related quality of life (HRQOL). Linear mixed models were used to determine the variables associated with dyspnea.
Results: Out of 503 patients (55% male, mean age 62.8 ± 14.6 years), 45%-64% of the participants had dyspnea at any time point. No significant change of dyspnea over time was found. Body mass index (estimate -0.04, 95% CI -0.06 to -0.02, p = 0.0002), symptoms of depression (estimate -0.11, 95% CI -0.15 to -0.07, p < 0.0001), symptoms of anxiety (estimate -0.08, 95% CI -0.11 to -0.04, p < 0.001), and FEV1 values (estimate 0.35, 95% CI 0.10-0.61, p = 0.0060) were significantly associated with the CRQ dyspnea score. Furthermore, dyspnea had significant and strong adverse associations with all subscales of the PEmb-QOL (p < 0.0001).
Discussion: Dyspnea is a common and persisting complaint after PE. Symptoms of depression and anxiety are strongly related with dyspnea and dyspnea is significantly associated with impaired HRQOL
LEOPARD: missing view completion for multi-timepoint omics data via representation disentanglement and temporal knowledge transfer
Get PDFLongitudinal multi-view omics data offer unique insights into the temporal dynamics of individual-level physiology, which provides opportunities to advance personalized healthcare. However, the common occurrence of incomplete views makes extrapolation tasks difficult, and there is a lack of tailored methods for this critical issue. Here, we introduce LEOPARD, an innovative approach specifically designed to complete missing views in multi-timepoint omics data. By disentangling longitudinal omics data into content and temporal representations, LEOPARD transfers the temporal knowledge to the omics-specific content, thereby completing missing views. The effectiveness of LEOPARD is validated on four real-world omics datasets constructed with data from the MGH COVID study and the KORA cohort, spanning periods from 3 days to 14 years. Compared to conventional imputation methods, such as missForest, PMM, GLMM, and cGAN, LEOPARD yields the most robust results across the benchmark datasets. LEOPARD-imputed data also achieve the highest agreement with observed data in our analyses for age-associated metabolites detection, estimated glomerular filtration rate-associated proteins identification, and chronic kidney disease prediction. Our work takes the first step toward a generalized treatment of missing views in longitudinal omics data, enabling comprehensive exploration of temporal dynamics and providing valuable insights into personalized healthcare
Serum metabolites characterize hepatic phenotypes and reveal shared pathways: results from population-based imaging
Get PDFBackground: Steatotic liver disease is a major public health issue, with hepatic iron overload exacerbating fibrotic conditions. This study aimed to identify metabolites associated with hepatic fat and/or iron overload using targeted metabolomics in a population-based cohort.
Methods: We used the cross-sectional KORA-MRI study (N = 376 individuals). Hepatic fat and iron content were derived by magnetic resonance imaging, and serum metabolite concentrations were quantified through targeted metabolomics. Associations between 146 metabolites and 40 indicators with hepatic phenotypes were analyzed, adjusted for confounders, and corrected for multiple testing. Formal pathway analyses and mediation analyses including genetic data were conducted. Performance of metabolomics to diagnose steatosis or hepatic iron overload was evaluated using ROC curves, and compared to the fatty liver index (FLI).
Results: Overall, 50.8% of participants (mean age 56.4 years) had hepatic steatosis, and 43.6% iron overload. Twelve unique metabolites/indicators (amino acids, lysophosphatidylcholine, acyl-alkyl-phosphatidylcholine), and sums of branched chain and aromatic amino acids, and five lipids, and ratio of acyl-alkyl-phosphatidylcholines to diacyl-phosphatidylcholines were associated with hepatic fat content. 27 metabolites/indicators, including 25 lipids, were associated with hepatic iron content. Addition of these metabolites to the FLI improved diagnosis of steatosis and iron overload nominally. Glycerophospholipid metabolism, phenylalanine, tyrosine and tryptophan biosynthesis and glycerophospholipid metabolism were shared pathway between steatosis and iron overload. Alanine, isoleucine, glutamine and pimeloylcarnitine (C7-DC) mediated effects between genetic variants and hepatic phenotypes.
Conclusion: Metabolites were associated with hepatic fat and iron content, shared common pathways, and improved diagnosis of steatosis and iron overload, highlighting the role of iron in hepatic disorders
Boundary-spanning by design? Policy-induced innovation collaboration in the German bioeconomy
Get PDFIn 2019, the German government introduced a new policy to spur field-spanning innovation synergies in the bioeconomy. The so-called ‘Innovation Space’ defines a funding umbrella around a specific bioeconomy subfield and delegates authority of decision-making on new grants and members to the initially funded consortium. In this paper, we explore the extent to which one Innovation Space focusing on bio-based textiles experienced knowledge cross-fertilization between distinct projects. We propose a typology of boundary-spanning knowledge relationships and apply a mixed relational methods approach to empirically assess the potential for knowledge cross-fertilization and, hence, policy-induced collaboration in the textile bioeconomy. Despite its recent emergence, we find incidence of boundary-spanning learning relations across projects and sectors (science–industry) since inception of the Innovation Space. Members with permanent or temporary geographical co-location, and those receiving referrals from colleagues, were more likely to engage in knowledge exchange than other members. Project managers were involved in two-thirds of boundary-spanning, whereas similar relationships between only technical members were rare. Additionally, analysis of network robustness shows that learning across project boundaries was vulnerable to already low membership fluctuation. The findings suggest that Innovation Spaces are a policy instrument that fosters knowledge cross-fertilization beyond the confines of bounded projects
Machine learning versus clinicians for detection and classification of oral mucosal lesions
No full textObjectives
The detection and classification of oral mucosal lesions is a challenging task due to high heterogeneity and overlap in clinical appearance. Nevertheless, differentiating benign from potentially malignant lesions is essential for appropriate management. This study evaluated whether a deep learning model trained to discriminate 11 classes of oral mucosal lesions could exceed the performance of general dentists.
Methods
4079 intraoral photographs of benign, potentially malignant and malignant oral lesions were labeled using bounding boxes and classified into 11 classes. The data were split 80:20 for training (n = 3031) and validation (n = 766), keeping an independent test set (n = 282). The YOLOv8 computer vision model was implemented for image classification and object detection. Model performance was evaluated on the test set which was also assessed by six general dentists and three specialists in oral surgery. Evaluation metrics included sensitivity, specificity, F1-score, precision, area under the receiver operating characteristic curve (AUROC), and average precision (AP) at multiple thresholds of intersection over union.
Results
In terms of classification, the highest F1-score (0.80) and AUROC (0.96) were observed for human papillomavirus (HPV)-related lesions, whereas the lowest F1-score (0.43) and AUROC (0.78) were obtained for keratosis. In terms of object detection, the best results were achieved for HPV-related lesions (AP25 = 0.82) and proliferative verrucous leukoplakia (AP25 = 0.80; AP50 = 0.76), while the lowest values were noted for leukoplakia (AP25 = 0.36; AP50 = 0.20). Overall, the model performed comparable to specialists (p = 0.93) and significantly better than general dentists (p < 0.01).
Conclusion
The developed model performed as well as specialists in oral surgery, highlighting its potential as a valuable tool for oral lesion assessment.
Clinical significance
By providing performance comparable to oral surgeons and superior to general dentists, the developed multi-class model could support the clinical evaluation of oral lesions, potentially enabling earlier diagnosis of potentially malignant disorders, enhancing patient management and improving patient prognosis
