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The rich chemical information from tissue metabolomics provides a powerful means to elaborate tissue physiology or tumor characteristics at cellular and tumor microenvironment levels. However, the process of obtaining such information requires invasive biopsies, is costly, and can delay clinical patient management. Conversely, computed tomography (CT) is a clinical standard of care but does not intuitively harbor histological or prognostic information. Furthermore, the ability to embed metabolome information into CT to subsequently use the learned representation for classification or prognosis has yet to be described. This study develops a deep learning-based framework -- tissue-metabolomic-radiomic-CT (TMR-CT) by combining 48 paired CT images and tumor/normal tissue metabolite intensities to generate ten image embeddings to infer metabolite-derived representation from CT alone. In clinical NSCLC settings, we ascertain whether TMR-CT results in an enhanced feature generation model solving histology classification/prognosis tasks in an unseen international CT dataset of 742 patients. TMR-CT non-invasively determines histological classes - adenocarcinoma/squamous cell carcinoma with an F1-score = 0.78 and further asserts patients’ prognosis with a c-index = 0.72, surpassing the performance of radiomics models and deep learning on single modality CT feature extraction. Additionally, our work shows the potential to generate informative biology-inspired CT-led features to explore connections between hard-to-obtain tissue metabolic profiles and routine lesion-derived image data.

ObjectivesTo evaluate tomosynthesis compared with 2D-mammography in cancer detection and recalls in a screening-programme, and assess performing synthesized instead of 2D, and compare double reading of 2D with single reading of tomosynthesis.MethodsWomen (age 50–69 years) participating in the screening-programme were included. 2D-mammography and tomosynthesis were performed. There were four reading models: 2D-mammography (first); 2D-mammography (second); tomosynthesis + synthesized (third); tomosynthesis + synthesized + 2D (fourth reading). Paired double reading of 2D (first+second) and tomosynthesis (third+fourth) were analysed.ResultsIn 16,067 participants, there were 98 cancers and 1,196 recalls. Comparing double reading of 2D with single reading of tomosynthesis, there was an increase of 12.6 % in cancer detection with the third reading (p= 0.043) and 6.9 % with the fourth reading (p=0.210), and a decrease in recalls of 40.5 % (p<0.001) and 44.4 % (p<0.001), respectively. With double reading of both techniques, there was an increase in cancer detection of 17.4 % (p = 0.004) and a decrease in recalls of 12.5 % (p = 0.001) with tomosynthesis.ConclusionSingle reading of tomosynthesis plus synthesized increased cancer detection and decreased recalls compared with double reading 2D. 2D did not improve results when added to tomosynthesis.Key Points• Tomosynthesis increases cancer detection and decreases recall rates versus 2D mammography.• Synthesized-mammography avoids performing 2D, showing higher cancer detection.• Single reading of tomosynthesis + synthesized is feasible as a new practice.

Background Prostate cancer (PCa) is a hormone-dependent tumor and one of the most prevalent cancers in men worldwide. PCa progression is influenced by its interaction with the surrounding tumor microenvironment, highlighting the role of periprostatic adipose tissue (PPAT), which modulates PCa behavior through the secretion of bioactive molecules (e.g., adipokines). However, the influence of this complex cell communication, particularly under altered metabolic conditions, remains to be fully elucidated. Methods We performed multiomic/bioinformatic approaches integrating transcriptomic, proteomic, and metabolomic data from PPATs and their secretome and circulating/urinary of lipocalin-2 (LCN2) levels using a well-characterized cohort [75 PCa-patients vs. 22 control subjects with benign prostate hyperplasia (BPH)]. Different prostate cell models [normal-like (PNT2) and PCa cells (DU145/LNCaP/22Rv1/PC-3)] were used to test the role of the LCN2/SLC22A17 axis in PCa cell via multiple functional (proliferation/apoptosis/migration/invasion/colony-formation/tumorsphere assays), molecular (transcriptomic/phospho-proteomic/targeted inflammatory proteomics), and preclinical (in vivo xenograft) analyses. External validation was performed using TCGA, Grasso, and Taylor cohorts, alongside longitudinal proteomic data from patient-derived xenograft models. Results A signature of significantly dysregulated adipokines was identified in PPAT of PCa vs. BPH patients. Unsupervised clustering analyses revealed two distinct molecular phenotypes (T1/T2) with unique adipokine fingerprints associated with differential obesity-related comorbidities (BMI/diabetes/dyslipidemia), being LCN2 the only adipokine showing consistent dysregulation at the transcriptomic/proteomic levels. Functional experiments demonstrated that LCN2 and its receptor SLC22A17 exert context- and transformation state-dependent effects [i.e., in vitro LCN2 and SLC22A17 overexpression promoting migration capacity in normal-like cells, while suppressing aggressive phenotypes (proliferation/invasion/stemness) in malignant models; these findings being also confirmed on in vivo xenograft models]. SLC22A17 expression was progressively lost during PCa progression and associated with significantly poorer survival across multiple independent cohorts. Mechanistically, LCN2 modulated critical oncogenic and inflammatory pathways, including NF-κB, TGF-β, JAK/STAT, and inflammasome-related signaling, and showed obesity-specific associations with arachidonic acid and complement components in the PPAT secretome. Conclusions These results demonstrate a profound dysregulation of the PPAT-derived adipokine profile in PCa associated with obesity-related comorbidities, and reveal a paradoxical, stage- and context-dependent dual role of the LCN2/SLC22A17 axis as a key modulator of PPAT-PCa microenvironment interactions, with potential implications for inflammation, metabolic signaling, and tumor progression. Graphical Abstract Plain English summary The fat tissue surrounding the prostate-gland, known as periprostatic adipose-tissue (PPAT), is not simply a passive energy store — it actively communicates with prostate cancer (PCa) cells by releasing signaling molecules called adipokines. Our study shows that this communication is profoundly altered in PCa patients, particularly in those with obesity, diabetes, or high cholesterol. By analyzing PPAT samples from a large group of patients and combining genetic/protein/metabolic data, we identified two distinct groups of PCa patients based on their adipokine profiles, each with different metabolic characteristics. Among all adipokines examined, lipocalin-2 (LCN2) and its receptor SLC22A17 stood out as a patho-physiologically relevant system. Interestingly, rather than simply promoting tumor growth, LCN2 appeared to behave differently depending on the context: in normal prostate cells it stimulated migration, whereas in cancer cells reduced aggressiveness features, a finding confirmed both in laboratory experiments and preclinical models. Moreover, SLC22A17 was progressively lost as the disease advanced, and patients with lower levels of both molecules had worse clinical outcomes. These findings suggest that LCN2/SLC22A17-axis plays a complex, context-dependent role in PCa that is strongly influenced by the metabolic environment shaped by the surrounding PPAT, and that obesity-related changes in PPAT may critically influence how PCa develops and progresses.

Interventional radiology (IR) has evolved rapidly, but the clinical integration of interventional radiologists has not kept pace with technical advancements. This trial will address a gap in the literature by providing a robust investigation into specific measures for enhancing the clinical role of interventional radiologists, with potential implications for improving patient experiences and outcomes. The single-center randomized controlled trial will include 428 patients undergoing IR procedures. The control group will receive information about the procedure from the ordering physician, while the experimental group will have an additional consultation with an interventional radiologist and be shown procedure-specific explanatory videos. The primary outcomes are patients’ knowledge, satisfaction with the information and communication, and anxiety. Data collection will involve specific questionnaires and scales. This trial is designed to investigate the importance of proactive clinical roles in patient care within IR. The study explores the potential of consultations and audiovisual tools, highlighting their role in educating patients about procedures. The results may help foster a more widespread acceptance of clinical responsibilities in IR and underscore the pivotal role of audiovisual aids in patient education and satisfaction. Trial registration NCT05461482 at clinicaltrials.gov. Relevance statement This randomized controlled trial will assess the impact of clinical consultations and explanatory audiovisual tools on patient understanding, satisfaction, and anxiety in interventional radiology. The findings could help establish a more proactive clinical role for interventional radiologists and improve the overall quality of patient-centered care. Key Points We describe the protocol of an interventional radiology randomized clinical trial. The control group will receive procedure information from the referring physician and the experimental group receives additional consultation with interventionalists and views a video. Knowledge, satisfaction with information, and patient anxiety will be evaluated. This study will provide insights about the benefits of consultations and videos in interventional radiology. Graphical Abstract

This study evaluated the use of TachoSil as an adjunctive therapy for reducing axillary lymphocele formation. Eighty-six patients diagnosed with breast cancer N+ and treated with axillary lymphadenectomy received a TachoSil patch in the axillary wound. Using a database of patients without placing a hemostatic patch, we applied a matched case–control in a 1-to-2 fashion. Multiple and logistic regression analyses were used to evaluate postoperative results. Patient group with TachoSil showed a significantly lower drainage volume (P < .001) and the length of stay was significantly shorter (P < .001). The number of patients with evacuative punctures was 24.5% in the group with patch versus 51.2% in the control group (P < .001). In multivariate analysis, the use of TachoSil was a significant predictor of reducing axillary drainage volume (P < .001), mean length of hospital stay (P = .001), and number of evacuative punctures of lymphocele (odds ratio .264, 95% confidence interval .144 to .484, P < .001). The use of TachoSil in axillary lymphadenectomy may be a safe and useful treatment option for reducing axillary drainage volume, incidence of symptomatic lymphocele, and hospital stay.

Objectives Preoperative breast magnetic resonance imaging (MRI) can inform surgical planning but might cause overtreatment by increasing the mastectomy rate. The Multicenter International Prospective Analysis (MIPA) study investigated this controversial issue. Methods This observational study enrolled women aged 18–80 years with biopsy-proven breast cancer, who underwent MRI in addition to conventional imaging (mammography and/or breast ultrasonography) or conventional imaging alone before surgery as routine practice at 27 centers. Exclusion criteria included planned neoadjuvant therapy, pregnancy, personal history of any cancer, and distant metastases. Results Of 5896 analyzed patients, 2763 (46.9%) had conventional imaging only (noMRI group), and 3133 (53.1%) underwent MRI that was performed for diagnosis, screening, or unknown purposes in 692/3133 women (22.1%), with preoperative intent in 2441/3133 women (77.9%, MRI group). Patients in the MRI group were younger, had denser breasts, more cancers ≥ 20 mm, and a higher rate of invasive lobular histology than patients who underwent conventional imaging alone ( p  < 0.001 for all comparisons). Mastectomy was planned based on conventional imaging in 22.4% (MRI group) versus 14.4% (noMRI group) ( p  < 0.001). The additional planned mastectomy rate in the MRI group was 11.3%. The overall performed first- plus second-line mastectomy rate was 36.3% (MRI group) versus 18.0% (noMRI group) ( p  < 0.001). In women receiving conserving surgery, MRI group had a significantly lower reoperation rate (8.5% versus 11.7%, p  < 0.001). Conclusions Clinicians requested breast MRI for women with a higher a priori probability of receiving mastectomy. MRI was associated with 11.3% more mastectomies, and with 3.2% fewer reoperations in the breast conservation subgroup. Key Points • In 19% of patients of the MIPA study, breast MRI was performed for screening or diagnostic purposes. • The current patient selection to preoperative breast MRI implies an 11% increase in mastectomies, counterbalanced by a 3% reduction of the reoperation rate. • Data from the MIPA study can support discussion in tumor boards when preoperative MRI is under consideration and should be shared with patients to achieve informed decision-making.

Background Traumatic brain injury (TBI) is characterized by a primary mechanical injury and a secondary injury associated with neuroinflammation, blood–brain barrier (BBB) disruption and neurodegeneration. We have developed a novel cannabidiol aminoquinone derivative, VCE-004.8, which is a dual PPARγ/CB 2 agonist that also activates the hypoxia inducible factor (HIF) pathway. VCE-004.8 shows potent antifibrotic, anti-inflammatory and neuroprotective activities and it is now in Phase II clinical trials for systemic sclerosis and multiple sclerosis. Herein, we investigated the mechanism of action of VCE-004.8 in the HIF pathway and explored its efficacy in a preclinical model of TBI. Methods Using a phosphoproteomic approach, we investigated the effects of VCE-004.8 on prolyl hydroxylase domain-containing protein 2 (PHD2) posttranslational modifications. The potential role of PP2A/B55α in HIF activation was analyzed using siRNA for B55α. To evaluate the angiogenic response to the treatment with VCE-004.8 we performed a Matrigel plug in vivo assay. Transendothelial electrical resistance (TEER) as well as vascular cell adhesion molecule 1 (VCAM), and zonula occludens 1 (ZO-1) tight junction protein expression were studied in brain microvascular endothelial cells. The efficacy of VCE-004.8 in vivo was evaluated in a controlled cortical impact (CCI) murine model of TBI. Results Herein we provide evidence that VCE-004.8 inhibits PHD2 Ser125 phosphorylation and activates HIF through a PP2A/B55α pathway. VCE-004.8 induces angiogenesis in vivo increasing the formation of functional vessel (CD31/α-SMA) and prevents in vitro blood–brain barrier (BBB) disruption ameliorating the loss of ZO-1 expression under proinflammatory conditions. In CCI model VCE-004.8 treatment ameliorates early motor deficits after TBI and attenuates cerebral edema preserving BBB integrity. Histopathological analysis revealed that VCE-004.8 treatment induces neovascularization in pericontusional area and prevented immune cell infiltration to the brain parenchyma. In addition, VCE-004.8 attenuates neuroinflammation and reduces neuronal death and apoptosis in the damaged area. Conclusions This study provides new insight about the mechanism of action of VCE-004.8 regulating the PP2A/B55α/PHD2/HIF pathway. Furthermore, we show the potential efficacy for TBI treatment by preventing BBB disruption, enhancing angiogenesis, and ameliorating neuroinflammation and neurodegeneration after brain injury.

Objective To assess clinical variables that may be useful in differentiating gynaecomastia from carcinoma and to analyse the contribution of mammography and ultrasound to the evaluation of male breast disease. Methods All men who underwent mammography and/or ultrasound between 1993 and 2006 in our hospital were retrospectively evaluated. Clinical characteristics in patients with gynaecomastia and those with carcinoma were compared. Radiological findings were classified according to the BI-RADS (Breast Imaging Reporting and Data System) criteria. The diagnostic performance of physical examination, mammography and ultrasound was determined and compared. Results A total of 628 patients with 518 mammograms and 423 ultrasounds were reviewed. The final diagnoses were: 19 carcinomas, 526 gynaecomastias, 84 other benign conditions and 25 normal. There were statistically significant differences in age, bilateral involvement, clinical presentation and physical examination between patients with carcinoma and those with gynaecomastia. The diagnostic performance of physical examination was lower than that of mammography and ultrasound ( p  < 0.05 for specificity). Mammography was the most sensitive (94.7%) and ultrasound the most specific (95.3%) for detection of malignancy ( p  > 0.05). We propose an algorithm for the use of mammography and ultrasound in men. Conclusions Mammography and ultrasound, with a negative predictive value close to 100%, make it possible to avoid very many unnecessary surgical procedures in men.