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Proteolytic degradation of peptide-based drugs is often considered as major weakness limiting systemic therapeutic applications. Therefore, huge efforts are typically devoted to stabilize sequences against proteases present in serum or plasma, obtained as supernatants after complete blood coagulation or centrifugation of blood supplemented with anticoagulants, respectively. Plasma and serum are reproducibly obtained from animals and humans allowing consistent for clinical analyses and research applications. However, the spectrum of active or activated proteases appears to vary depending on the activation of proteases and cofactors during coagulation (serum) or inhibition of such enzymes by anticoagulants (plasma), such as EDTA (metallo- and Ca2+-dependent proteases) and heparin (e.g. thrombin, factor Xa). Here, we studied the presumed effects on peptide degradation by taking blood via cardiac puncture of CD-1 mice using a syringe containing a peptide solution. Due to absence of coagulation activators (e.g. glass surfaces and damaged cells), visible blood clotting was prevented allowing to study peptide degradation for one hour. The remaining peptide was quantified and the degradation products were identified using mass spectrometry. When the degradation rates (half-life times) were compared to serum derived freshly from the same animal and commercial serum and plasma samples, peptides of three different families showed indeed considerably different stabilities. Generally, peptides were faster degraded in serum than in plasma, but surprisingly all peptides were more stable in fresh blood and the order of degradation rates among the peptides varied among the six different incubation experiments. This indicates, that proteolytic degradation of peptide-based therapeutics may often be misleading stimulating efforts to stabilize peptides at degradation sites relevant only in vitro, i.e., for serum or plasma stability assays, but of lower importance in vivo.

Clinically relevant postoperative pancreatic fistula (CR-POPF) is a common severe surgical complication after pancreatic surgery. Current risk stratification systems mostly rely on intraoperatively assessed factors like manually determined gland texture or blood loss. We developed a preoperatively available image-based risk score predicting CR-POPF as a complication of pancreatic head resection. Frequency of CR-POPF and occurrence of salvage completion pancreatectomy during the hospital stay were associated with an intraoperative surgical (sFRS) and image-based preoperative CT-based (rFRS) fistula risk score, both considering pancreatic gland texture, pancreatic duct diameter and pathology, in 195 patients undergoing pancreatic head resection. Based on its association with fistula-related outcome, radiologically estimated pancreatic remnant volume was included in a preoperative (preFRS) score for POPF risk stratification. Intraoperatively assessed pancreatic duct diameter ( p  < 0.001), gland texture ( p  < 0.001) and high-risk pathology ( p  < 0.001) as well as radiographically determined pancreatic duct diameter ( p  < 0.001), gland texture ( p  < 0.001), high-risk pathology ( p  = 0.001), and estimated pancreatic remnant volume ( p  < 0.001) correlated with the risk of CR-POPF development. PreFRS predicted the risk of CR-POPF development (AUC = 0.83) and correlated with the risk of rescue completion pancreatectomy. In summary, preFRS facilitates preoperative POPF risk stratification in patients undergoing pancreatic head resection, enabling individualized therapeutic approaches and optimized perioperative management.

Oxidized phospholipids (oxPLs) have been recently recognized as important mediators of various and often controversial cellular functions and stress responses. Due to the low concentrations in vivo , oxPL detection is mostly performed by targeted mass spectrometry. Although significantly improving the sensitivity, this approach does not provide a comprehensive view on oxPLs required for understanding oxPL functional activities. While capable of providing information on the diversity of oxPLs, the main challenge of untargeted lipidomics is the absence of bioinformatics tools to support high-throughput identification of previously unconsidered, oxidized lipids. Here, we present LPPtiger, an open-source software tool for oxPL identification from data-dependent LC-MS datasets. LPPtiger combines three unique algorithms to predict oxidized lipidome, generate oxPL spectra libraries, and identify oxPLs from tandem MS data using parallel processing and a multi-scoring identification workflow.

ObjectivesTo perform a systematic review and meta-analysis of published data to evaluate the utility of chemical shift imaging (CSI) for differentiating between adrenal adenomas and non-adenomas.MethodsA systematic search of the MEDLINE, Web of Science Core Collection, EMBASE and Cochrane Central Register of Controlled Trials electronic databases was performed. The methodological quality of the included studies was assessed by using the QUADAS-2 (Quality Assessment of Diagnostic Accuracy Studies) tool. A bivariate random effect model was used to determine summary and subgroup sensitivity and specificity and calculate summary receiver operating characteristic curves (SROC).ResultsEighteen studies with 1138 patients and 1280 lesions (859 adenomas, 421 non-adenomas) in total were included. In addition to summary analysis, quantitative analyses of the adrenal signal intensity index (SII, 978 lesions, 14 studies), adrenal-to-spleen ratio (ASR; 394 lesions, 7 studies) and visual analysis (560 lesions, 5 studies) were performed. The resultant data showed considerable heterogeneity (inconsistency index I2 of 94%, based on the diagnostic odds ratio, DOR). The pooled sensitivity of CSI for adenoma was 0.94 [95% confidence interval (CI) 0.88–0.97] and pooled specificity was 0.95 (95% CI 0.89–0.97). The area (AUC) under the SROC curve was 0.98 (95% CI 0.96–0.99). The corresponding AUCs were 0.98, 0.99 and 0.95 for SII, ASR and visual evaluation, respectively.ConclusionCSI has high sensitivity, specificity and accuracy for adrenal adenoma. Diagnostic performance does not improve when quantitative indices are used.Key Points• Inclusion of CSI in abdominal MRI protocols provides an effective solution for classifying adrenal masses discovered on MR exams• Visual evaluation of adrenal CSI is sufficient; use of quantitative indices does not improve diagnostic accuracy

To examine the comparative robustness of computed tomography (CT)-based conventional radiomics and deep-learning convolutional neural networks (CNN) to predict overall survival (OS) in HCC patients. Retrospectively, 114 HCC patients with pretherapeutic CT of the liver were randomized into a development (n = 85) and a validation (n = 29) cohort, including patients of all tumor stages and several applied therapies. In addition to clinical parameters, image annotations of the liver parenchyma and of tumor findings on CT were available. Cox-regression based on radiomics features and CNN models were established and combined with clinical parameters to predict OS. Model performance was assessed using the concordance index (C-index). Log-rank tests were used to test model-based patient stratification into high/low-risk groups. The clinical Cox-regression model achieved the best validation performance for OS (C-index [95% confidence interval (CI)] 0.74 [0.57–0.86]) with a significant difference between the risk groups (p = 0.03). In image analysis, the CNN models (lowest C-index [CI] 0.63 [0.39–0.83]; highest C-index [CI] 0.71 [0.49–0.88]) were superior to the corresponding radiomics models (lowest C-index [CI] 0.51 [0.30–0.73]; highest C-index [CI] 0.66 [0.48–0.79]). A significant risk stratification was not possible (p > 0.05). Under clinical conditions, CNN-algorithms demonstrate superior prognostic potential to predict OS in HCC patients compared to conventional radiomics approaches and could therefore provide important information in the clinical setting, especially when clinical data is limited.

Objectives Multidisciplinary tumour boards (MTBs) play an increasingly important role in managing cancer patients from diagnosis to treatment. However, many problems arise around the organisation of MTBs, both in terms of organisation-administration and time management. In this context, the European Society of Oncologic Imaging (ESOI) conducted a survey among its members, aimed at assessing the quality and amount of involvement of radiologists in MTBs, their role in it and related issues. Methods All members were invited to fill in a questionnaire consisting of 15 questions with both open and multiple-choice answers. Simple descriptive analyses and graphs were performed. Results A total of 292 ESOI members in full standing for the year 2018 joined the survey. Most respondents (89%) declared to attend MT-Bs, but only 114 respondents (43.9%) review over 70% of exams prior to MTB meetings, mainly due to lack of time due to a busy schedule for imaging and reporting (46.6%). Perceived benefits (i.e. surgical and histological feedback (86.9%), improved knowledge of cancer treatment (82.7%) and better interaction between radiologists and referring clinicians for discussing rare cases (56.9%)) and issues (i.e. attending MTB meetings during regular working hours (71.9%) and lack of accreditation with continuing medical education (CME) (85%)) are reported. Conclusions Despite the value and benefits of radiologists’ participation in MTBs, issues like improper preparation due to a busy schedule and no counterpart in CME accreditation require efforts to improve the role of radiologists for a better patient care. Key Points • Most radiologists attend multidisciplinary tumour boards, but less than half of them review images in advance, mostly due to time constraints. • Feedback about radiological diagnoses, improved knowledge of cancer treatment and interaction with referring clinicians are perceived as major benefits. • Concerns were expressed about scheduling multidisciplinary tumour boards during regular working hours and lack of accreditation with continuing medical education.

Objectives The aim of the study was to evaluate the effect of bolus-tracking ROI positioning on coronary computed tomography angiography (CCTA) image quality. Methods In this retrospective monocentric study, all patients had undergone CCTA by step-and-shoot mode to rule out coronary artery disease within a cohort at intermediate risk. Two groups were formed, depending on ROI positioning (left atrium (LA) or ascending aorta (AA)). Each group contained 96 patients. To select pairs of patients, propensity score matching was used. Image quality with regard to coronary arteries as well as pulmonary arteries was evaluated using quantitative and qualitative scores. Results In terms of the coronary arteries, there was no significant difference between both groups using quantitative (SNR AA 14.92 vs. 15.46; p = 0.619 | SNR LM 19.80 vs. 20.30; p = 0.661 | SNR RCA 24.34 vs. 24.30; p = 0.767) or qualitative scores (4.25 vs. 4.29; p = 0.672), respectively. With regard to pulmonary arteries, we found significantly higher quantitative (SNR RPA 8.70 vs. 5.89; p < 0.001 | SNR LPA 9.06 vs. 6.25; p < 0.001) and qualitative scores (3.97 vs. 2.24; p < 0.001) for ROI positioning in the LA than for ROI positioning in the AA. Conclusions ROI positioning in the LA or the AA results in comparable image quality of CT coronary arteriography, while positioning in the LA leads to significantly higher image quality of the pulmonary arteries. These results support ROI positioning in the LA, which also facilitates triple-rule-out CT scanning. Key Points • ROI positioning in the left atrium or the ascending aorta leads to comparable image quality of the coronary arteries. • ROI positioning in the left atrium results in significantly higher image quality of the pulmonary arteries. • ROI positioning in the left atrium is feasible to perform triple-rule-out CTA.

Background Sarcopenia, characterized by loss of skeletal muscle mass and strength, is prevalent in patients undergoing treatment for colorectal cancer. Sarcopenia's prevalence in patients with cancer can reach up to 50% and is known to exacerbate postsurgical complications and affect long‐term oncological outcomes. This study examined whether minimally invasive surgery (MIS) offers protective benefits against postoperative sarcopenia compared with open surgery in patients undergoing rectal cancer resection. Methods This retrospective analysis included 145 patients who underwent open or minimally invasive (laparoscopic or robot‐assisted) rectal resections at the University Hospital Dresden between 2013 and 2021. Confounding variables were adjusted using propensity score matching. The skeletal muscle index (SMI) and psoas muscle thickness per height (PMTH) were analysed in preoperative and postoperative computed tomography scans to measure changes in skeletal muscle mass. Potential risk factors for muscle loss were evaluated, and oncological long‐term outcome was analysed. Results The results indicate that oncological rectal resection did not result in pronounced postoperative muscle loss. No significant difference between the open and MIS groups in terms of postoperative muscle loss over 3 years postoperatively could be detected. Wound healing disorders were identified as the most significant independent risk factors for muscle loss (SMI loss > 10%). In contrast, neither the type of surgical technique nor the presence of a protective loop ileostomy significantly influenced the development of postoperative muscle loss. Patients who experienced a > 10% SMI loss within the first year had significantly poorer overall and disease‐free survival. The 1‐year survival rate was 93.3% in the group with high SMI loss compared with 100.0% in the group with low SMI loss (p = 0.435). The 3‐year (66.7% vs. 95.6%, HR 8.75, 95% CI 1.855–41.286, p = 0.006) and 5‐year (44.4% vs. 93.3%, HR 11.072, 95% CI 2.414–50.782, p = 0.002) survival rates were significantly lower in patients with high SMI loss. Patients with high SMI loss had an increased likelihood of recurrence and metastasis. Conclusions Although MIS did not confer a protective advantage against postoperative muscle loss in patients with rectal cancer, the findings highlight the critical role of maintaining muscle mass in improving survival outcomes. Postoperative muscle loss appears to be a marker of aggressive tumour behaviour, and interventions aimed at minimizing muscle loss, such as enhanced nutritional support, may improve the long‐term patient prognosis. Future studies should explore interventional strategies to mitigate sarcopenia in this population.

Clinically relevant postoperative pancreatic fistula (CR-POPF) can significantly affect the treatment course and outcome in pancreatic cancer patients. Preoperative prediction of CR-POPF can aid the surgical decision-making process and lead to better perioperative management of patients. In this retrospective study of 108 pancreatic head resection patients, we present risk models for the prediction of CR-POPF that use combinations of preoperative computed tomography (CT)-based radiomic features, mesh-based volumes of annotated intra- and peripancreatic structures and preoperative clinical data. The risk signatures were evaluated and analysed in detail by visualising feature expression maps and by comparing significant features to the established CR-POPF risk measures. Out of the risk models that were developed in this study, the combined radiomic and clinical signature performed best with an average area under receiver operating characteristic curve (AUC) of 0.86 and a balanced accuracy score of 0.76 on validation data. The following pre-operative features showed significant correlation with outcome in this signature ( p < 0.05 ) - texture and morphology of the healthy pancreatic segment, intensity volume histogram-based feature of the pancreatic duct segment, morphology of the combined segment, and BMI. The predictions of this pre-operative signature showed strong correlation (Spearman correlation co-efficient, ρ = 0.7 ) with the intraoperative updated alternative fistula risk score (ua-FRS), which is the clinical gold standard for intraoperative CR-POPF risk stratification. These results indicate that the proposed combined radiomic and clinical signature developed solely based on preoperatively available clinical and routine imaging data can perform on par with the current state-of-the-art intraoperative models for CR-POPF risk stratification.

Sample preparation is the most critical step in proteomics as it directly affects the subset of proteins and peptides that can be reliably identified and quantified. Although a variety of efficient and reproducible sample preparation strategies have been developed, their applicability and efficacy depends much on the biological sample. Here, three approaches were evaluated for the human milk and plasma proteomes. Protein extracts were digested either in an ultrafiltration unit (filter-aided sample preparation, FASP) or in-solution (ISD). ISD samples were desalted by solid-phase extraction prior to nRPC-ESI-MS/MS. Additionally, milk and plasma samples were directly digested by FASP without prior protein precipitation. Each strategy provided inherent advantages and disadvantages for milk and plasma. FASP appeared to be the most time efficient procedure with a low miscleavage rate when used for a biological sample aliquot, but quantitation was less reproducible. A prior protein precipitation step improved the quantitation by FASP due to significantly higher peak areas for plasma and a much better reproducibility for milk. Moreover, the miscleavage rate for milk, the identification rate for plasma, and the carbamidomethylation efficiency were improved. In contrast, ISD of both milk and plasma resulted in higher miscleavage rates and is therefore less suitable for targeted proteomics.