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Background: Technological progress in the acquisition of medical images and the extraction of underlying quantitative imaging data has introduced exciting prospects for the diagnostic assessment of a wide range of conditions. This study aims to investigate the diagnostic utility of a machine learning classifier based on dual-energy computed tomography (DECT) radiomics for classifying pulmonary embolism (PE) severity and assessing the risk for early death., Methods: Patients who underwent CT pulmonary angiogram (CTPA) between January 2015 and March 2022 were considered for inclusion in this study. Based on DECT imaging, 107 radiomic features were extracted for each patient using standardized image processing. After dividing the dataset into training and test sets, stepwise feature reduction based on reproducibility, variable importance and correlation analyses were performed to select the most relevant features; these were used to train and validate the gradient-boosted tree models., Results: The trained machine learning classifier achieved a classification accuracy of .90 for identifying high-risk PE patients with an area under the receiver operating characteristic curve of .59. This CT-based radiomics signature showed good diagnostic accuracy for risk stratification in individuals presenting with central PE, particularly within higher risk groups., Conclusion: Models utilizing DECT-derived radiomics features can accurately stratify patients with pulmonary embolism into established clinical risk scores. This approach holds the potential to enhance patient management and optimize patient flow by assisting in the clinical decision-making process. It also offers the advantage of saving time and resources by leveraging existing imaging to eliminate the necessity for manual clinical scoring., (© 2023 The Authors. European Journal of Clinical Investigation published by John Wiley & Sons Ltd on behalf of Stichting European Society for Clinical Investigation Journal Foundation.)

Background and Purpose: Development of core concepts in disciplines such as biochemistry, microbiology and physiology have transformed teaching. They provide the foundation for the development of teaching resources for global educators, as well as valid and reliable approaches to assessment. An international research consensus recently identified 25 core concepts of pharmacology. The current study aimed to define and unpack these concepts., Experimental Approach: A two-phase, iterative approach, involving 60 international pharmacology education experts, was used. The first phase involved drafting definitions for core concepts and identifying key sub-concepts via a series of online meetings and asynchronous work. These were refined in the second phase, through a 2-day hybrid workshop followed by a further series of online meetings and asynchronous work., Key Results: The project produced consensus definitions for a final list of 24 core concepts and 103 sub-concepts of pharmacology. The iterative, discursive methodology resulted in modification of concepts from the original study, including change of 'drug-receptor interaction' to 'drug-target interaction' and the change of the core concept 'agonists and antagonists' to sub-concepts of drug-target interaction., Conclusions and Implications: Definitions and sub-concepts of 24 core concepts provide an evidence-based foundation for pharmacology curricula development and evaluation. The next steps for this project include the development of a concept inventory to assess acquisition of concepts, as well as the development of case studies and educational resources to support teaching by the global pharmacology community, and student learning of the most critical and fundamental concepts of the discipline., (© 2023 The Authors. British Journal of Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.)

Background: To investigate the potential of radiomic features and dual-source dual-energy CT (DECT) parameters in differentiating between benign and malignant mediastinal masses and predicting patient outcomes., Methods: In this retrospective study, we analysed data from 90 patients (38 females, mean age 51 ± 25 years) with confirmed mediastinal masses who underwent contrast-enhanced DECT. Attenuation, radiomic features and DECT-derived imaging parameters were evaluated by two experienced readers. We performed analysis of variance (ANOVA) and Chi-square statistic tests for data comparison. Receiver operating characteristic curve analysis and Cox regression tests were used to differentiate between mediastinal masses., Results: Of the 90 mediastinal masses, 49 (54%) were benign, including cases of thymic hyperplasia/thymic rebound (n = 10), mediastinitis (n = 16) and thymoma (n = 23). The remaining 41 (46%) lesions were classified as malignant, consisting of lymphoma (n = 28), mediastinal tumour (n = 4) and thymic carcinoma (n = 9). Significant differences were observed between benign and malignant mediastinal masses in all DECT-derived parameters (p ≤ .001) and 38 radiomic features (p ≤ .044) obtained from contrast-enhanced DECT. The combination of these methods achieved an area under the curve of .98 (95% CI, .893-1.000; p < .001) to differentiate between benign and malignant masses, with 100% sensitivity and 91% specificity. Throughout a follow-up of 1800 days, a multiparametric model incorporating radiomic features, DECT parameters and gender showed promising prognostic power in predicting all-cause mortality (c-index = .8 [95% CI, .702-.890], p < .001)., Conclusions: A multiparametric approach combining radiomic features and DECT-derived imaging biomarkers allows for accurate and noninvasive differentiation between benign and malignant masses in the anterior mediastinum., (© 2023 The Authors. European Journal of Clinical Investigation published by John Wiley & Sons Ltd on behalf of Stichting European Society for Clinical Investigation Journal Foundation.)

Background: Cancer is a well-known risk factor for venous thromboembolism (VTE). A combined strategy of D-dimer testing and clinical pre-test probability is usually used to exclude VTE. However, its effectiveness is diminished in cancer patients due to reduced specificity, ultimately leading to a decreased clinical utility. This review article seeks to provide a comprehensive summary of how to interpret D-dimer testing in cancer patients., Methods: In accordance with PRISMA standards, literature pertaining to the diagnostic and prognostic significance of D-dimer testing in cancer patients was carefully chosen from reputable sources such as PubMed and the Cochrane databases., Results: D-dimers have not only a diagnostic value in ruling out VTE but can also serve as an aid for rule-in if their values exceed 10-times the upper limit of normal. This threshold allows a diagnosis of VTE in cancer patients with a positive predictive value of more than 80%. Moreover, elevated D-dimers carry important prognostic information and are associated with VTE reoccurrence. A gradual increase in risk for all-cause death suggests that VTE is also an indicator of biologically more aggressive cancer types and advanced cancer stages. Considering the lack of standardization for D-dimer assays, it is essential for clinicians to carefully consider the variations in assay performance and the specific test characteristics of their institution., Conclusions: Standardizing D-dimer assays and developing modified pretest probability models specifically for cancer patients, along with adjusted cut-off values for D-dimer testing, could significantly enhance the accuracy and effectiveness of VTE diagnosis in this population., (© 2023 The Authors. European Journal of Clinical Investigation published by John Wiley & Sons Ltd on behalf of Stichting European Society for Clinical Investigation Journal Foundation.)

Background and Purpose: In recent decades, a focus on the most critical and fundamental concepts has proven highly advantageous to students and educators in many science disciplines. Pharmacology, unlike microbiology, biochemistry, or physiology, lacks a consensus list of such core concepts., Experimental Approach: We sought to develop a research-based, globally relevant list of core concepts that all students completing a foundational pharmacology course should master. This two-part project consisted of exploratory and refinement phases. The exploratory phase involved empirical data mining of the introductory sections of five key textbooks, in parallel with an online survey of over 200 pharmacology educators from 17 countries across six continents. The refinement phase involved three Delphi rounds involving 24 experts from 15 countries across six continents., Key Results: The exploratory phase resulted in a consolidated list of 74 candidate core concepts. In the refinement phase, the expert group produced a consensus list of 25 core concepts of pharmacology., Conclusion and Implications: This list will allow pharmacology educators everywhere to focus their efforts on the conceptual knowledge perceived to matter most by experts within the discipline. Next steps for this project include defining and unpacking each core concept and developing resources to help pharmacology educators globally teach and assess these concepts within their educational contexts., (© 2022 The Authors. British Journal of Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.)

Background: D-dimer testing is known to have a high sensitivity at simultaneously low specificity, resulting in nonspecific elevations in a variety of conditions., Methods: This retrospective study sought to assess diagnostic and prognostic features of D-dimers in cancer patients referred to the emergency department for suspected pulmonary embolism (PE) and deep vein thrombosis (DVT). In total, 526 patients with a final adjudicated diagnosis of PE (n = 83) and DVT (n = 69) were enrolled, whereas 374 patients served as the comparative group, in which venous thromboembolism (VTE) has been excluded., Results: For the identification of VTE, D-dimers yielded the highest positive predictive value of 96% (95% confidence interval (CI), 85-99) at concentrations of 9.9 mg/L and a negative predictive value of 100% at .6 mg/L (95% CI, 97-100). At the established rule-out cut-off level of .5 mg/L, D-dimers were found to be very sensitive (100%) at a moderate specificity of nearly 65%. Using an optimised cut-off value of 4.9 mg/L increased the specificity to 95% for the detection of life-threatening VTE at the cost of moderate sensitivities (64%). During a median follow-up of 30 months, D-dimers positively correlated with the reoccurrence of VTE (p = .0299) and mortality in both cancer patients with VTE (p < .0001) and without VTE (p = .0008)., Conclusions: Although D-dimer testing in cancer patients is discouraged by current guidelines, very high concentrations above the 10-fold upper reference limit contain diagnostic and prognostic information and might be helpful in risk assessment, while low concentrations remain useful for ruling out VTE., (© 2022 The Authors. European Journal of Clinical Investigation published by John Wiley & Sons Ltd on behalf of Stichting European Society for Clinical Investigation Journal Foundation.)

Whole-body magnetic resonance imaging (MRI) has become increasingly popular in oncology. However, the long acquisition time might hamper its widespread application. We sought to assess and compare free-breathing sequences with conventional breath-hold examinations in whole-body MRI using an automated workflow process. This prospective study consisted of 20 volunteers and six patients with a variety of pathologies who had undergone whole-body 1.5-T MRI that included T1-weighted radial and Dixon volumetric interpolated breath-hold examination sequences. Free-breathing sequences were operated by using an automated user interface. Image quality, diagnostic confidence, and image noise were evaluated by two experienced radiologists. Additionally, signal-to-noise ratio was measured. Diagnostic performance for the overall detection of pathologies was assessed using the area under the receiver operating characteristics curve (AUC). Study participants were asked to rate their examination experiences in a satisfaction survey. MR free-breathing scans were rated as at least equivalent to conventional MR scans in more than 92% of cases, showing high overall diagnostic accuracy (95% [95% CI 92-100]) and performance (AUC 0.971, 95% CI 0.942-0.988; p < 0.0001) for the assessment of pathologies at simultaneously reduced examination times (25 ± 2 vs. 32 ± 3 min; p < 0.0001). Interrater agreement was excellent for both free-breathing (ϰ = 0.96 [95% CI 0.88-1.00]) and conventional scans (ϰ = 0.93 [95% CI 0.84-1.00]). Qualitative and quantitative assessment for image quality, image noise, and diagnostic confidence did not differ between the two types of MR image acquisition (all p > 0.05). Scores for patient satisfaction were significantly better for free-breathing compared with breath-hold examinations (p = 0.0145), including significant correlations for the grade of noise (r = 0.79, p < 0.0001), tightness (r = 0.71, p < 0.0001), and physical fatigue (r = 0.52, p = 0.0065). In summary, free-breathing whole-body MRI in tandem with an automated user interface yielded similar diagnostic performance at equivalent image quality and shorter acquisition times compared to conventional breath-hold sequences., (© 2022 The Authors. NMR in Biomedicine published by John Wiley & Sons Ltd.)

Catechin is found in several natural sources, as Eugenia dysenterica and Syzygium cumini extracts. Its antioxidant and UV-protective properties suggest a potential use in cosmetic and dermatological formulations. A simple analytical method capable of giving support to experiments performed along the development of topical formulations containing this natural substance (i.e. drug assay, skin permeation and stability studies), however, is still needed. Thus, this work aimed to develop and validate a selective HPLC method for catechin determination during the development of topical formulations. Separation was achieved using an RP-C 18 column (300 × 3.9 mm; 10 μm), with a mobile phase of methanol-phosphoric acid 0.01 m (15: 85, v/v), a flow rate of 0.8 mL/min, temperature set at 40°C and UV detection at 230 nm. The method was linear in a range from 0.5 to 10.0 μg/mL (r = 0.9998), precise with an overall variation coefficient of 5.5% and accurate with catechin recovery from the skin layers >85%. Additionally, the method was sensitive (limit of detection, 0.109 μg/mL; limit of quantification, 0.342 μg/mL) and selective against plant extracts, skin matrices and formulation interferents, as well as catechin degradation products. It was also robust regarding both methodology parameters and analytical stability., (Copyright © 2017 John Wiley & Sons, Ltd.)

Background: Clinical trials comparing mastectomy to conservative surgery plus radiation therapy in the treatment of breast cancer have provided an opportunity to increase understanding of the biology of this disease and the psychological adaptation of the breast cancer patient. Because these local treatments appear to be equal in terms of survival, the question remains as to whether conservative surgery plus radiation therapy confers a measure of psychological comfort superior to that of mastectomy for women diagnosed with early-stage breast cancer., Methods: One hundred forty-two women participating in a clinical trial randomizing patients to mastectomy or lumpectomy and radiation therapy were prospectively evaluated for psychological response to their respective local therapy. A baseline assessment before randomization and subsequent questionnaires at 6, 12, and 24 months after treatment were completed by patients entered in the clinical trial., Results: At 6 months, mastectomy patients reported significantly less control over events in their lives (P = 0.003) and more problems with sexual relations (P = 0.021) than did their conservatively treated counterparts. In addition, there were marked differences between mastectomy patients and lumpectomy and radiation therapy patients in the degree of distress over their nude bodies, with P = 0.001 at 6 months, P = 0.019 at 12 months, and P = 0.057 at 24 months., Conclusions: From our findings, it appears that breast conservation therapy protects women's perception of their body but does not, over time, contribute to a more positive sexual adjustment.

One hundred and one soft tissue sarcoma patients from an adjuvant chemotherapy study of the Surgery Branch, National Cancer Institute who had received greater than or equal to 430 mg/m2 (range, 430-600 mg/m2) of doxorubicin were followed for evidence of cardiomyopathy. Fourteen patients developed clinical congestive heart failure attributable to doxorubicin. Nine of these fourteen were evaluated by radionuclide angiography (RNA), and all were abnormal with mean ejection fraction both at rest and exercise less than 30%. Sixty-one asymptomatic patients were studied at least once with RNA. In this asymptomatic group, 13 of 61 patients (21%) had abnormal resting left ventricular function. Exercise studies identified an additional 19 abnormal individuals (31%). Overall incidence of cardiomyopathy, as evidenced by RNA, in the asymptomatic group was 52%. By including the fourteen symptomatic patients, the incidence of cardiomyopathy detected either clinically or by RNA in the 75 evaluated patients was 46%. Comparison of patients by age (less than 40 versus greater than 40) revealed a highly significant difference in the incidence of cardiomyopathy (P less than .001). Fourteen of 36 patients (38%) less than or equal to 40 had either clinical or RNA evidence of cardiotoxicity while 32 of 39 (82%) individuals greater than 40 demonstrated cardiomyopathy. No significant difference was seen in those asymptomatic patients in whom RNA was performed less than or equal to 12 months as compared with greater than 12 months after the end of doxorubicin treatment. In the entire group there was no apparent improvement in cardiomyopathy with time, but results suggest that left ventricular function in the group older than 40 years does deteriorate. The cardiac function of patients younger than age 40 appeared to remain stable or possibly improve with time after the completion of treatment. Sex, tumor location, and radiation treatment were not associated with an increased risk of cardiomyopathy. These results emphasize the dangers of full-dose doxorubicin therapy. This high incidence of cardiomyopathy became apparent because of our ability to prospectively evaluate a large group of patients with prolonged life expectancy that received adjuvant doxorubicin chemotherapy after surgery.