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Objective: The ketogenic diet or exogenous supplementation with 3-hydroxybutyrate (3HB) is progressively gaining recognition as a valuable therapeutic or health intervention strategy. However, the effects of 3HB on cancers have been inconsistent in previous studies. This study aimed to comprehensively investigate the causal effects of circulating 3HB levels on 120 cancer phenotypes, and explore the 3HB mediation effect between liver fat accumulation and cancers., Methods: Univariate Mendelian randomization (UVMR) was used in this study to investigate the causal impact of circulating 3HB levels on cancers. We conducted meta-analyses for 3HB-cancer associations sourced from different exposure data. In multivariate MR(MVMR), the body mass index, alcohol frequency and diabetes were included as covariates to investigate the independent effect of 3HB on cancer risk. Additionally, utilizing mediation MR analysis, we checked the potential mediating role of 3HB in the association between liver fat and cancer., Results: Integrating findings from UVMR and MVMR, we observed that elevated circulating 3HB levels were associated with reduced risk of developing diffuse large B-cell lymphoma(DLBCL) (OR[95%CI] = 0.28[0.14-0.57] p = 3.92e-04), biliary malignancies (OR[95%CI] = 0.30[0.15-0.60], p = 7.67e-04), hepatocellular carcinoma(HCC) (OR[95%CI] = 0.25[0.09-0.71], p = 9.33e-03), primary lymphoid and hematopoietic malignancies (OR[95%CI] = 0.76[0.58-0.99], p = 0.045). Further UVMR analysis revealed that an increase in the percent liver fat was associated with reduced 3HB levels (Beta[95%CI] = -0.073[-0.122∼-0.024], p = 0.0034) and enhanced susceptibility to HCC (OR[95%CI] = 13.9[9.76-19.79], p = 3.14e-48), biliary malignancies (OR[95%CI] = 4.04[3.22-5.07], p = 1.64e-33), nasopharyngeal cancer (OR[95%CI] = 3.26[1.10-9.67], p = 0.03), and primary lymphoid and hematopoietic malignancies (OR[95%CI] = 1.27[1.13-1.44], p = 1.04e-4). Furthermore, 3HB fully mediated the effect of liver fat on susceptibility to DLBCL (OR[95%CI] = 1.076[1.01-1.15], p = 0.034)., Conclusions: Circulating 3HB is associated with a reduced susceptibility to developing DLBCL, HCC, biliary malignancies, and primary lymphoid and hematopoietic malignancies. The impaired ketogenesis induced by metabolic-dysfunction associated fatty liver disease (MAFLD) contributes to risk of DLBCL., Competing Interests: Conflict of interest The authors declare that they have no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Continuously improving cancer-specific survival puts a growing proportion of cancer patients at risk of major adverse cardiovascular events (MACE), but tailored tools for cardiovascular risk prediction remain unavailable., Objectives: To assess a broad panel of cardiovascular biomarkers and risk factors for the prediction of MACE and cardiovascular death in cancer patients., Methods: In total, 2192 patients with newly diagnosed or recurrent cancer were followed prospectively for the occurrence of 2-year MACE and 5-year cardiovascular death. Univariable and multivariable risk models were fit to assess independent associations of cardiovascular risk factors and biomarkers with adverse outcomes, and a risk score was developed., Results: Traditional cardiovascular risk factors and selected cancer types were linked to higher MACE risk. While levels of Lp(a), CRP, and GDF-15 did not associate with MACE, levels of ICAM-1, P-/E-/L-selectins, and NT-proBNP were independently linked to 2-year MACE risk. A clinical risk score was derived, assigning +1 point for male sex, smoking, and age of ≥60 years and +2 points for atherosclerotic disease, yielding a bootstrapped C-statistic of 0.76 (95% CI: 0.71-0.81) for the prediction of 2-year MACE. Implementation of biomarker data conferred improved performance (0.83, 95% CI: 0.78-0.88), with a simplified model showing similar performance (0.80, 95% CI: 0.74-0.86). The biomarker-enhanced and simplified prediction models achieved a C-statistic of 0.82 (95% CI: 0.71-0.93) and 0.74 (95% CI: 0.64-0.83) for the prediction of 5-year cardiovascular death., Conclusion: Biomarker-enhanced risk prediction strategies allow the identification of cancer patients at high risk of MACE and cardiovascular death. While external validation studies are ongoing, this first-of-its-kind risk score may provide the basis for personalized cardiovascular risk assessment across cancer entities., Competing Interests: Declaration of competing interests S.K. has received funding from the Jubiläumsstiftung SwissLife, the Lindenhof Foundation, the Novartis Foundation for Medical-Biological Research, the Swiss Heart Foundation, the Swiss Society of Cardiology, and the Theodor-Ida-Herzog-Egli Foundation, and materials and equipment from Roche Diagnostics. He has received travel support from the European Atherosclerosis Society, the European Society of Cardiology, the European Society of Clinical Investigation, Sphingotec GmbH, the 4TEEN4 Pharmaceuticals GmbH, and the PAM Theragnostics GmbH. L.L. is a co-inventor on the international patent WO/2020/226993 filed in April 2020. The patent relates to the use of antibodies that specifically bind IL-1α to reduce various sequelae of ischemia–reperfusion injury to the central nervous system. He further reports speaker fees from Daiichi Sankyo outside the submitted work. Moreover, he is counselor of the European Society for Clinical Investigation and has received fundings from the Novartis Foundation for Medical-Biological Research, the Swiss Heart Foundation, and the Italian Ministry of Health. T.M.S. declares funding from the Lindenhof Foundation. F.A.W. is supported by a grant of the Lindenhof Foundation (through S.K., T.F.L, and T.M.S.) and the Foundation for Cardiovascular Research—Zurich Heart House. He has received funding from the Fonds zur Förderung des akademischen Nachwuchses of the University of Zurich, the European Society of Cardiology, 4TEEN4 Pharmaceuticals GmbH, PAM Theragnostics GmbH, and Sphingotec GmbH outside the submitted work. Outside this work, I.P. reports honoraria for lectures from Bayer, BMS/Pfizer, and Sanofi and participation in advisory boards from Bayer and BMS/Pfizer. Outside this work, T.F.L. declares research and educational grants to the institution from Abbott, Amgen, AstraZeneca, Boehringer Ingelheim, Daiichi Sankyo, Menarini Foundation, Novartis, Novo Nordisk, Roche Diagnostics, Sanofi, and Vifor and honoraria from Amgen, Dacadoo, Daiichi Sankyo, Menarini Foundation, Novartis, Novo Nordisk, Philips, and Pfizer. He holds leadership positions at the European Society of Cardiology, Swiss Heart Foundation, and the Foundation for Cardiovascular Research—Zurich Heart House. C.A. reports honoraria for lectures from Bayer, Daiichi Sankyo, BMS/Pfizer, and Sanofi and participation in advisory boards from Bayer, Boehringer Ingelheim, Daiichi Sankyo, and BMS/Pfizer. F.Moik reports honoraria for lectures from BMS and MSD and participation in advisory boards from BMS. All other authors have no competing interests to disclose., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

In the rapidly evolving field of medical diagnostics, biomarkers play a pivotal role, particularly in the early detection of cancer. Cluster of differentiation 5 (CD5), a cell surface glycoprotein found on T cells and B-1a lymphocytes, is instrumental in immune regulation and is associated with both autoimmune diseases and malignancies. Despite its significant diagnostic and therapeutic potential, CD5 detection has been limited by modern methods in the pg/ml range. This study presents a novel multimodal electrochemical immunosensor that employs laser-processed Ti/Au electrodes for the ultra-sensitive detection of CD5 in human blood serum. The "multimodal" approach combines different analytical techniques - differential pulse volctammetry (DPV) and electrochemical impedance spectroscopy (EIS) - to ensure comprehensive analysis, enhancing both the accuracy and reliability of the sensor. This novel sensor significantly outperforms existing commercial ELISA kits, achieving a limit of detection (LOD) of 1.1 ± 0.2 fg/mL with DPV and 3.9 ± 0.5 fg/mL with EIS in phosphate-buffered saline (PBS) and 6.6 ± 3.1 fg/mL and 15.6 ± 3.1 fg/mL in human serum (HS), respectively. These results highlight the immunosensor's potential for improving early-stage cancer diagnosis and broader medical applications., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Igor Iatsunskyi reports financial support was provided by Adam Mickiewicz University. Igor Iatsunskyi reports a relationship with Adam Mickiewicz University that includes: employment., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Conventional blood-based biomarkers and radiographic imaging are excellent for use in monitoring different aspects of malignant disease, but given their specific shortcomings, their integration with other, complementary markers such as plasma circulating tumor DNA (ctDNA) will be beneficial toward a precision medicine-driven future. Plasma ctDNA analysis utilizes the measurement of cancer-specific molecular alterations in a variety of bodily fluids released by dying tumor cells to monitor and profile response to therapy, and is being employed in several clinical scenarios. Plasma concentrations of ctDNA have been reported to correlate with tumor burden. However, the strength of this association is generally poor and highly variable, confounding the interpretation of longitudinal plasma ctDNA measurements in conjunction with routine radiographic assessments. Herein is discussed what is currently understood with respect to the fundamental characteristics of tumor growth that dictate plasma ctDNA concentrations, with a perspective on its interpretation in conjunction with radiographically determined tumor burden assessments., Competing Interests: Disclosure Statement None declared., (Copyright © 2024 Association for Molecular Pathology and American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

Background and Aim: Lead (Pb) is a toxic heavy metal and pervasive environmental contaminant, and a class 2 A carcinogen according to the IARC classification, yet its link with cancer at several body sites remains uncertain. Here, we aimed at summarizing the scientific evidence regarding its association with cancer risk and mortality, focusing on studies that carried out Pb measurements in biological samples., Methods: We reviewed articles published in PubMed and EMBASE until January 2nd, 2024, that quantified the epidemiological association between Pb measured in blood, urine, nails, and other biological media, and cancer risk and mortality (overall and by cancer site/type)., Results: We included 46 articles (out of 8022 screened) published in 1995-2023 and reporting on investigations conducted in fifteen countries. In terms of design, 20 were prospective, 24 were retrospective case-control studies, and 2 were cross-sectional. Pb levels were determined in blood in the majority of studies (n=28). The most consistent evidence was for the association of Pb with cancer of the gastrointestinal tract, particularly the oesophagus, stomach (RR ranging from 0.80 to 2.66), colon-rectum, and pancreas; and of the bladder and urinary tract (RR from 1.10 to 2.89). For other specific malignancies, the data were conflicting or too limited to draw reliable conclusions. Finally, increased Pb concentration in blood and urine was consistently associated with higher overall cancer incidence and mortality., Conclusions: Lead is a widespread and highly persistent environmental pollutant associated with cancer at multiple body sites. Comprehensive primary prevention interventions aiming at reducing opportunities for Pb exposure need to be continuously promoted and implemented., Competing Interests: Declaration of Competing Interest The 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 Elsevier Ltd. All rights reserved.)

Background: The potential role of n-6 PUFAs in major health outcomes remains controversial., Objectives: To examine the relationship between the major plasma n6 PUFA, linoleic acid (LA), as well as the non-LA n6 PUFAs, and total and cause-specific mortality., Methods: This was a prospective, observational, biomarker-based study in the UK Biobank. Individuals with complete information on baseline demographic, covariate and plasma PUFA levels (percent ot total fatty acids) and mortality outcomes were included (n=257,925). Multivariable-adjusted, Cox-proportional hazards models were used to predict risk of death from all-causes, and from cardiovascular disease (CVD), cancer, and other causes as a function of plasma LA and non-LA n6 levels, both continuously and by PUFA quintile (Q)., Results: Comparing LA Q5 to Q1, the hazard ratio (HR, 95% CI) for total mortality was 0.80 (0.76, 0.84; p<0.001), and this was similar for all three cause-specific death categories. On the other hand, mortality HR for non-LA n6 was 1.12 (1.08,1.17; p<0.001), and this was primarily due to increased risk for non-CVD, noncancer deaths [HR 1.29 (1.19,1.40; p<0.001)]. Exploratory analyses among the eight next most common other causes of death suggested that both the decreased risk associated with higher LA and the increased risk associated with non-LA n6 were confined to deaths from respiratory and digestive diseases., Conclusions: These findings highlight the profound differences in mortality risk related to LA and non-LA n6 PUFA levels and underscore the inappropriateness of treating n-6 PUFAs as a homogenous class with respect to health outcomes. They also support recommendations to maintain (if not increase) current LA intakes., (Copyright © 2024 American Society for Nutrition. Published by Elsevier Inc. All rights reserved.)

Preclinical studies have demonstrated that liposomal irinotecan (CPT-11), a topoisomerase I inhibitor, has broad activity against adult cancers, including pancreatic, gastric, colon, lung, glioma, ovarian, and breast cancer. Encapsulation of irinotecan into liposomes can modify its pharmacokinetic properties dramatically. Also, the pharmacokinetic profiles of liposomal drug formulations are not fully understood; thus, bioanalytical methods are needed to separate and quantify nonencapsulated vs. encapsulated concentrations. In this study, two robust, specific, and sensitive LC-MS/MS methods were developed and validated to separate and quantify the nonencapsulated CPT-11 (NE-CPT-11) from the sum-total CPT-11 (T-CPT-11) and its major metabolite, SN-38, in human plasma after intravenous administration of liposomal irinotecan. NE-CPT-11 and SN-38 were separated from plasma samples by using solid-phase extraction, and T-CPT-11 was measured by protein precipitation. The liposomal CPT-11 formulation was unstable during sample storage and handling, resulting in elevated NE-CPT-11 concentration. To improve the stability of liposomal CPT-11, a cryoprotectant solution was added to human plasma samples prior to storage and processing. CPT-11, SN-38, and their respective internal standards, CPT-11-d10 and SN-38-d3, were chromatographically separated on a reversed-phase C 18 analytical column. The drugs were detected on a triple quadrupole mass spectrometer in the positive MRM ion mode by monitoring the transitions 587.3 > 124.1 (CPT-11) and 393.0 > 349.1 (SN-38). The calibration curves demonstrated a good fit across the concentration ranges of 10-5000 ng/mL for T-CPT-11, 2.5-250 ng/mL for NE-CPT-11, and 1-500 ng/mL for SN-38. The accuracy and precision were within the acceptable limits, matrix effects were nonsignificant, recoveries were consistent and reproducible, and the analytes were stable under all tested storage conditions. Finally, the LC-MS/MS methods were successfully applied in a phase I clinical pharmacokinetic study of nanoliposomal irinotecan (Onivyde®) in pediatric patients with recurrent solid malignancies or Ewing sarcoma., Competing Interests: Declaration of competing interest The 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 Elsevier B.V. All rights reserved.)

Cancer has become the second leading cause of death in the world, and more than 50% of cancer patients are diagnosed at an advanced stage. Early diagnosis of tumours is the key to improving patient quality of life and survival time and reducing the socioeconomic burden. However, there is still a lack of reliable early diagnosis methods in clinical practice. In recent years, liquid biopsy technology has developed rapidly. It has the advantages of noninvasiveness, easy access to sample sources, and reproducibility. It has become the main focus of research on the early diagnosis methods of tumours. This review summarises the research progress of existing liquid biopsy markers, such as circulating tumour DNA, circulating viral DNA, DNA methylation, circulating tumour cells, circulating RNA, exosomes, and tumour education platelets in early diagnosis of tumours, and analyses the current advantages and limitations of various markers, providing a direction for the application and transformation of liquid biopsy research in early diagnosis of clinical tumours., Competing Interests: Declaration of competing interest The 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 Elsevier Ltd. All rights reserved.)

Circulating tumor cells (CTCs) are tumor cells that exist in human peripheral blood, which could spread to other tissues or organs via the blood circulation system and develop into metastatic foci, leading to tumor recurrence or metastasis in postoperative patients and thereby increasing the mortality of malignant tumor patients. Evaluation of CTC levels can be used for tumor metastasis prediction, prognosis evaluation, drug exploitation, individualized treatment, liquid biopsy, etc., which exhibit outstanding clinical application prospects. In recent years, accurately capturing and analyzing CTCs has become a research hotspot in the early diagnosis and precise treatment of tumors. This review summarized various enrichment and isolation technologies for evaluating CTCs based on the design principle and discussed the challenges and perspectives in this field., Competing Interests: Declaration of competing interest The 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 Elsevier B.V. All rights reserved.)

Background and Objective: The ability to sense the biological microenvironment surrounding early-stage tumor tissues is critical for tumorigenesis tracing and tumor detection and treatment. An efficient tumor microenvironment (TME) sensing strategy remains a significant challenge. We propose a novel "seeing is sensing" approach that has the potential to discern the whole-blood viscosity (WBV) information of the TME by using a swarm of nanoswimmers (NS)., Methods: In this study, we employ statistical mechanics methods to derive the relationship between the aggregation of NS in the microscale and their macroscopic concentration distribution. We utilize the finite difference method to develop a discrete numerical model of the NS diffusion in the blood. We further develop a novel model for TME sensing that can dynamically detect the WBV by analyzing the kinematic motion of the NS swarm, which enables real-time detection of WBV by observing the Full Width at Half Maximum (FWHM) of the NS swarm motion., Results: The viscosity value obtained with our sensing method is benchmarked against the gold standard results obtained from the Brookfield viscometer. The measurements obtained from both methods exhibit an excellent correlation, with a coefficient of determination (R 2 ) of 0.9617. Furthermore, the constructed Bland-Altman plot reveals that the majority of observed data points lie within the limits of agreement of the 95% clinical confidence interval (lower limit of agreement = -0.0660, upper limit of agreement = 0.1130), thus validating the feasibility of our sensing strategy., Conclusions: We present a new sensing strategy that utilizes the diffusion dynamics of the NS swarm within the vascular network to infer variations in WBV. Comparative analysis with gold standard data substantiates the accuracy and applicability of this method in assessing WBV parameters in the vicinity of tumor tissues. Our work demonstrates relevant prospects for visualizing, comprehending, and evaluating the pathological progression of blood-related disorders in real-time., Competing Interests: Declaration of competing interest We declare that all the authors have no financial or personal relationships with other people or organizations that can inappropriately influence our work. There is no professional or other personal interest of any nature or kind in any product, service, and/or company that could be construed as influencing the position presented in the manuscript entitled., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Now, genomics forms the core of the precision medicine concept. Comprehensive investigations of tumor genomes have made it possible to characterize tumors at the molecular level and, specifically, to identify the fundamental processes that cause condition. A variety of kinds of tumors have seen better outcomes for patients as a result of the development of novel medicines to tackle these genetic-driving processes. Since therapy may exert selective pressure on cancers, non-invasive methods such as liquid biopsies can provide the opportunity for rich reservoirs of crucial and real-time genetic data. Liquid biopsies depend on the identification of circulating cells from tumors, circulating tumor DNA (ctDNA), RNA, proteins, lipids, and metabolites found in patient biofluids, as well as cell-free DNA (cfDNA), which exists in those with cancer. Although it is theoretically possible to examine biological fluids other than plasma, such as pleural fluid, urine, saliva, stool, cerebrospinal fluid, and ascites, we will limit our discussion to blood and solely cfDNA here for the sake of conciseness. Yet, the pace of wider clinical acceptance has been gradual, partly due to the increased difficulty of choosing the best analysis for the given clinical issue, interpreting the findings, and delaying proof of value from clinical trials. Our goal in this review is to discuss the current clinical value of ctDNA in cancers and how clinical oncology systems might incorporate procedures for ctDNA testing., Competing Interests: Declaration of competing interest The Authors declare they have no conflict of interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Epidemiological evidence indicates an association between exposure to toxic metals and the occurrence of cardiometabolic diseases (CMDs). However, the impact of exposure to harmful metallic elements, such as lead (Pb), cadmium (Cd), and mercury (Hg), on mortality in individuals with cardiometabolic multimorbidity (CMM) remains uncertain. Therefore, in this study, we analyzed data from 4139 adults diagnosed with CMM from the National Health and Nutrition Examination Survey 1999-2016. CMM was defined as the presence of at least two CMDs (hypertension, diabetes, stroke, and coronary artery disease). Over an average follow-up period of 9.0 years, 1379 deaths from all causes, 515 deaths related to cardiovascular disease (CVD), and 215 deaths attributable to cancer were recorded. After adjusting for potential covariates, serum Pb concentrations were not associated with all-cause, CVD, or cancer mortality. Participants exposed to Cd had an elevated risk of all-cause mortality (hazard ratio [HR], 1.23; 95 % CI, 1.16-1.30), CVD-related mortality (HR, 1.23; 95 % CI, 1.12-1.35), and cancer-related mortality (HR, 1.29; 95 % CI, 1.13-1.47). Participants with serum Hg levels in the highest quantile had lower risks of all-cause (HR, 0.64; 95 % CI, 0.52-0.80) and CVD-related (HR, 0.62; 95 % CI, 0.44-0.88) mortality than did those in the lowest quantile. Stratified analyses revealed significant interactions between serum Cd concentrations and age for CVD-related mortality (P for interaction =0.011), indicating that CMM participants aged < 60 years who were exposed to Cd were at a greater risk of CVD-related mortality. A nonlinear relationship was observed between serum Cd concentrations and all-cause (P for nonlinear relationship = 0.012) and CVD-related (P for nonlinear relationship < 0.001) mortality. Minimizing Cd exposure in patients with CMM may help prevent premature death., Competing Interests: Declaration of Competing Interest The 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 Authors. Published by Elsevier Inc. All rights reserved.)

Background & Aims: Our study aims to determine whether myostatin (MSTN) is associated with muscle mass and strength in individuals with cancer or obesity, as well as with cancer cachexia (CC) or sarcopenic obesity (SO)., Methods: The ACTICA study included individuals with CC (n = 70) or without CC (NC, n = 73). The MYDIASECRET study included individuals with obesity evaluated before (T0) and 3 months (T3) after bariatric surgery (n = 62). Body composition was assessed using bioelectrical impedance analysis (BIA). Skeletal muscle mass (SMM) and appendicular SMM (ASMM) were calculated from Janssen's and Sergi's equations, respectively, and expressed as indexes (SMMI and ASMMI). Handgrip strength (HGS) was assessed using a Jamar hand-held dynamometer. MSTN plasma levels were measured using ELISA. Spearman's coefficient was used to correlate MSTN with muscle mass and strength. Receiver operating characteristic (ROC) curve analysis was performed to identify an optimal MSTN cutoff level for the prediction of CC or SO., Results: In the ACTICA study, muscle mass and strength were lower in CC individuals than in NC individuals (SMMI: 8.0 kg/m 2 vs 9.0 kg/m 2 , p = 0.004; ASMMI: 6.2 kg/m 2 vs 7.2 kg/m 2 , p < 0.001; HGS: 28 kg vs 38 kg, p < 0.001). MSTN was also lower in CC individuals than in NC individuals (1434 pg/mL vs 2149 pg/mL, p < 0.001). Muscle mass and strength were positively correlated with MSTN (SMMI: R = 0.500, p < 0.001; ASMMI: R = 0.479, p < 0.001; HGS: R = 0.495, p < 0.001). ROC curve analysis showed a MSTN cutoff level of 1548 pg/mL (AUC 0.684, sensitivity 57%, specificity 75%, p < 0.001) for the prediction of CC. In the MYDIASECRET study, muscle mass and strength were reduced at T3 (SMMI: -8%, p < 0.001; ASMMI: -12%, p < 0.001; HGS: -6%, p = 0.005). MSTN was also reduced at T3 (1773 pg/mL vs 2582 pg/mL, p < 0.001). Muscle mass and strength were positively correlated with MSTN at T0 and T3 (SMMI-T0: R = 0.388, p = 0.002; SMMI-T3: R = 0.435, p < 0.001; HGS-T0: R = 0.337, p = 0.007; HGS-T3: R = 0.313, p = 0.013). ROC curve analysis showed a MSTN cutoff level of 4225 pg/mL (AUC 0.835, sensitivity 98%, specificity 100%, p = 0.014) for the prediction of SO at T3., Conclusions: MSTN is positively correlated with muscle mass and strength in individuals with cancer or obesity, suggesting its potential use as a biomarker of muscle mass and strength. The ROC curve analysis suggests the potential use of MSTN as a screening tool for CC and SO., Competing Interests: Conflict of interest The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objectives: [ 51 Cr]CrEDTA is used to measure the Glomerular Filtration Rate (GFR) in different clinical conditions. However, there is no consensus on the ideal number of blood samples to be taken and at what time points to measure its clearance. This study aimed to compare Slope Intercept (SI) and Single-Sample (SS) methods for measuring GFR in patients with solid tumors, stratified by age, GFR, and Body Mass Index (BMI)., Methods: 1,174 patients with cancer were enrolled in this prospective study. GFR was calculated by the SI method using blood samples drawn 2-, 4-, and 6-hours after [ 51 Cr]CrEDTA injection (246-GFR). GFR was also measured using the SI method with samples at 2 and 4 hours (24-GFR) and at 4 and 6 hours (46-GFR), and SS methods according to Groth (4Gr-GFR) and Fleming (4Fl-GFR). Statistical analysis was performed to assess the accuracy, precision, and bias of the methods., Results: Mean 246-GFR was 79.2 ± 21.9 mL/min/1.73 m 2 . ANOVA indicated a significant difference between 4Gr-GFR and the reference 246-GFR. Bias was lower than 5 mL/min/1.73 m 2 for all methods, except for SS methods in subgroups BMI > 40 kg/m 2 ; GFR > 105 or < 45. Precision was adequate and accuracy of 30 % was above 98% for all methods, except for SS methods in subgroup GFR < 45., Conclusion: 46-GFR and 246-GFR have high agreement and may be used to evaluate kidney function in patients with solid tumors. Single-sample methods can be adopted in specific situations, for non-obese patients with expected normal GFR., Competing Interests: Conflicts of interest The authors declare no conflicts of interest., (Copyright © 2024. Published by Elsevier España, S.L.U.)

Cancer detection is still a major challenge in public health. Identification of oncogene is the first step toward solving this problem. Studies have revealed that various cancers are associated with miRNA expression. Therefore, the sensitive detection of miRNA is substantially important to solve the cancer problem. In this study, let-7a, a representative substance of miRNA, was selected as the detection target. With the assistance of magnetic beads commonly used in biosensors and self-synthesized graphene oxide materials, specificity and sensitivity detection of the target gene let-7a were achieved via protease-free signal amplification. The limit of detection (LOD) was as low as 15.015pM. The fluorescence signal intensity showed a good linear relationship with the logarithm of let-7a concentration. The biosensor could also detect let-7a in complex human serum samples. Overall, this fluorescent biosensor is not only simple to operate, but also strongly specificity to detect let-7a. Therefore, it has substantial potential for application in the early diagnosis of clinical medicine and biological research., Competing Interests: Declaration of competing interest The 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 Elsevier B.V. All rights reserved.)

The role of C Reactive Protein (CRP) in predicting long-term outcomes among people living with cancer has not been well explored. We aimed to assess the role of elevated CRP in predicting all-cause mortality among a community-based sample of adult Americans living with cancer. The National Health and Nutrition Examination Survey, 1999-2010 was linked with mortality files up to December 2019 from the National Death Index. Sociodemographic and health-related variables of 30,711 participants (mean age=46.5 years) were analyzed to compute adjusted hazard ratios (HR) for all-cause mortality. The risk of mortality, in unadjusted analysis, was significantly higher among those with cancer compared to those without cancer 3.53 (95% CI= 3.13-3.98, p < 0.001). In adjusted analysis, when stratified by CRP levels (elevated=cutoff point at ≥2 mg/dL), among individuals with elevated CRP but no cancer history, the risk of mortality was significantly higher (HR=1.67, 95% CI=1.24-2.25) compared to those without cancer or elevated CRP. Among individuals with cancer but without elevated CRP as well, the risk of mortality was 20% higher compared to their counterparts. The highest risk of mortality was observed among those with both cancer and elevated CRP (HR=2.10, 95% CI=1.11-4.33). Age and income were significant predictors of these relationships. Among people living with cancer, CRP may serve as a marker for mortality and future studies should explore the pathways by which the risk of mortality may increase due to variation of CRP in cancer patients., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest to disclose for this manuscript and the study conducted for the manuscript., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Elevated serum methylmalonic acid (MMA), a marker of cobalamin (vitamin B12) deficiency, has been linked to cancer progression. However, the impact of MMA or cobalamin on mortality risk in cancer survivors remains unknown., Objectives: To explore the relationship between MMA, serum, dietary, and supplement of cobalamin, MMA metabolism-related genes, and poor prognosis in adult cancer survivors., Methods: We analyzed data from 1988 cancer survivors aged ≥20 y. Patients were selected from the National Health and Nutrition Examination Survey and followed up until December 31, 2019. Weighted Cox proportional hazard regression was used to estimate hazard ratios (HRs) and the corresponding 95% confidence intervals (CIs) for mortality risk assessment. Genomic analysis identified MMA metabolism-related genes linked to early death in a 33-cancer-type cohort from The Cancer Genome Atlas., Results: Among 1988 participants, 872 deaths occurred over a 10-year follow-up. Higher serum MMA levels were significantly linked to increased long-term mortality risk (tertile 3 compared with tertile 1: adjusted HR: 1.37; 95% CI: 1.11, 1.70; P-trend < 0.001). No associations were found between serum, dietary, and supplement of cobalamin and cancer survivor mortality (each P-trend > 0.143). However, MMA-associated mortality was notable in patients without deficiency. When combining cobalamin and MMA categories, multivariate-adjusted HR (95% CI) for all-cause mortality was 2.06 (95% CI: 1.60, 2.65) in participants with >250 nmol/L and cobalamin >295.1 pmol/L compared with those with MMA ≤250 nmol/L and cobalamin >295.1 pmol/L. Moreover, reduced transcriptional levels of MMA metabolism-related genes, indicating decreased mitochondrial MMA metabolism capability, are linked to an unfavorable prognosis in certain cancer types., Conclusions: Serum MMA was associated with long-term mortality risk in adult cancer survivors, which was more significant among individuals with higher levels of serum cobalamin. These findings suggest that mortality related to MMA was attributed to the insufficient flux of MMA metabolism, not cobalamin deficiency., (Copyright © 2024 American Society for Nutrition. Published by Elsevier Inc. All rights reserved.)

Cancer occupies the second place in terms of worldwide mortality. Early and fast diagnosis of cancer helps clinicians to expand therapeutic approaches ultimately leading towards early diagnosis of cancer patients. In the present work, we delineated an amperometric immunosensor to diagnose cancer to detect p53, a biomarker for cancer. The immunosensor was fabricated by immobilizing anti-p53 antibodies onto the pencil graphite electrode (PGE). The immobilization of probe was studied by scanning electron microscopy (SEM), electrochemical impedance spectroscopy (EIS) and cyclic voltammetry (CV). The immunosensor was optimized for pH, incubation temperature, antibody concentration, incubation time and antigen concentration. The developed immunosensor, showed a linear range between 10 pgmL -1 to 10 ngmL -1 with a detection limit (LOD) of 10 pgmL -1 . p53 antigen was analyzed by measuring current under optimal conditions. The occurrence of p53 was determined in sera of prostate, breast, colon and lung cancer patients by the present immunosensor. The lower incubation time i.e., fast response and lower LOD demonstrated an improved p53 immunosensor for early diagnosis of cancer., (Copyright © 2021. Published by Elsevier Inc.)

We have developed a real-time and multifunctional doxifluridine-conjugate prodrug (LYX), which involved the preliminary methylfluorescein with 5-fluorouracil linker as protecting group, the targeting biotin unit, and a model therapeutic drug (doxifluridine). The shielding group (5'-DFUR) was found to be effective in prolonging circulation at physiological pH 7.4 and improving accumulation in the acidic microenvironment of the tumor. Based on this strategy, the stability and stimulus responsive properties of prodrug could enhance drug release efficiency and exhibit fewer side effects, thereby providing a unique opportunity for diagnosis and imaging additional analytes or enzymatic activities., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Technological advances, in particular the development of high-throughput sequencing, have led to the emergence of a new generation of molecular biomarkers for tumors. These new tools have profoundly changed therapeutic management in oncology, with increasingly precise molecular characterization of tumors leading to increasingly personalized therapeutic targeting. Detection of circulating tumor cells and/or circulating tumor DNA in blood samples -so-called 'liquid biopsies'- can now provide a genetic snapshot of the patient's tumor through an alternative and less invasive procedure than biopsy of the tumor tissue itself. This procedure for characterizing and monitoring the disease in real time facilitates the search for possible relapses, the emergence of resistance, or emergence of a new therapeutic target. In the long term, it might also provide a means of early detection of cancer. These new approaches require the treatment of ever-increasing amounts of clinical data, notably, with the goal of calculating composite clinical-biological predictive scores. The use of artificial intelligence will be unavoidable in this domain, but it raises ethical questions and implications for the health-care system that will have to be addressed., (Copyright © 2021 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)

In oncology, the identification of targets that correlate with a type of cancer has led to a profound change in the notion of "tumor markers". Technological advances, in particular the development of high-throughput sequencing, have led to the emergence of a new generation of molecular biomarkers for tumors. Despite their limited utility for screening and diagnosis, conventional tumor markers remain interesting for evaluation of prognoses, the choice and optimization of treatments, as well as for monitoring the effectiveness of those treatments. In this article, we revisit the conventional serum markers that are enjoying a 'come back' thanks to the development of high-performance scores based on biological, cytological, clinical, or radiological criteria., (Copyright © 2021 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)

Advances in understanding the molecular mechanisms of tumor progression have achieved impressive progress in the treatment of cancer and so-called immune checkpoint inhibitors (ICIs) have revolutionized cancer therapy. Indeed, antibody-based drugs blocking immune escape of tumor cells by modulation of T cell responses are increasingly utilized for a wide range of tumor entities. Nonetheless, response rates remain limited, and the development of secondary resistance is a common problem. In addition, by increasing the immune response a variety of severe side effects are provoked. Next to autoimmune responses, activation of the complement system and skin toxicity, an increased incidence for thrombotic complications has been observed associated with an increased mortality rate. Based on this, it can be postulated that the interplay of coagulation with inflammation in the tumor microenvironment is relevant for each step in the tumor life cycle. This review focuses on the coagulation as central player fostering mechanisms associated with tumor progression. Thus, a better understanding of the molecular pathways involved in the complex interaction of circulating tumor cells, the plasmatic coagulation and immune cells may help to improve therapeutic concepts reducing mortality and morbidity associated with cancer., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Receptor tyrosine kinase-like orphan receptor 1 (ROR1) is highly expressed in a wide variety of hematological and solid cancers, but is low or absent in adult tissues. Here, we show that ROR1 is released with exosomes from ROR1-positive cancer cells. We also developed a simple dissociation-enhanced lanthanide fluorescence immunoassay (DELFIA) to detect cancer-derived ROR1-positive exosomes, which are captured by two anti-ROR1 antibodies and detected by the fluorescence of free chelating europium. This new DELFIA method can detect cancer-derived ROR1-positive exosomes in the cell supernatant and serum with a wide range and rapidly compared with the conventional Western blot assay. This method may be useful as a companion diagnostics for ROR1-positive cancers., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Aim: To establish a highly sensitive time-resolved fluorescence immunoassay of heparin-binding protein (HBP-TRFIA) and evaluate its application value for bacterial or fungal infections in tumor patients., Methods: Two types of HBP monoclonal specific antibodies against different epitopes of the antigen molecule were used as coating antibodies and Eu 3+ -labeled antibodies, respectively. The double-antibody sandwich method was used in establishing HBP-TRFIA, and the methodology was evaluated. The established HBP-TRFIA was used in detecting HBP concentration in the plasma samples of healthy individuals, patients with bacterial or fungal infections, and infected or uninfected patients with various types of tumors., Results: The linear range of HBP-TRFIA was (0.11-530 ng/mL). Plasma HBP concentrations detected through HBP-TRFIA were consistent with the results of fluorescence quantitative immunochromatography (ρ = 0.964). The plasma HBP concentrations of infected tumor patients were significantly higher than those of uninfected tumor patients (P < 0.01)., Conclusion: This study successfully established a highly sensitive HBP-TRFIA, which was highly comparable to commercially available fluorescent quantitative immunochromatographic kits and was able to facilitate the timely diagnosis of bacterial or fungal infections in patients with tumor., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Evidence-based guidelines recommend management strategies for malignant pleural effusions (MPEs) based on life expectancy. Existent risk-prediction rules do not provide precise individualized survival estimates., Research Question: Can a newly developed continuous risk-prediction survival model for patients with MPE and known metastatic disease provide precise survival estimates?, Study Design and Methods: Single-center retrospective cohort study of patients with proven malignancy, pleural effusion, and known metastatic disease undergoing thoracentesis from 2014 through 2017. The outcome was time from thoracentesis to death. Risk factors were identified using Cox proportional hazards models. Effect-measure modification (EMM) was tested using the Mantel-Cox test and was addressed by using disease-specific models (DSMs) or interaction terms. Three DSMs and a combined model using interactions were generated. Discrimination was evaluated using Harrell's C-statistic. Calibration was assessed by observed-minus-predicted probability graphs at specific time points. Models were validated using patients treated from 2010 through 2013. Using LENT (pleural fluid lactate dehydrogenase, Eastern Cooperative Oncology Group performance score, neutrophil-to-lymphocyte ratio and tumor type) variables, we generated both discrete (LENT-D) and continuous (LENT-C) models, assessing discrete vs continuous predictors' performances., Results: The development and validation cohort included 562 and 727 patients, respectively. The Mantel-Cox test demonstrated interactions between cancer type and neutrophil to lymphocyte ratio (P < .0001), pleural fluid lactate dehydrogenase (P = .029), and bilateral effusion (P = .002). DSMs for lung, breast, and hematologic malignancies showed C-statistics of 0.72, 0.72, and 0.62, respectively; the combined model's C-statistics was 0.67. LENT-D (C-statistic, 0.60) and LENT-C (C-statistic, 0.65) models underperformed., Interpretation: EMM is present between cancer type and other predictors; thus, DSMs outperformed the models that failed to account for this. Discrete risk-prediction models lacked enough precision to be useful for individual-level predictions., (Copyright © 2021 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Whole genome sequencing (WGS) using fresh-frozen tissue and matched blood samples from cancer patients may become the most complete genetic tumor test. With the increasing availability of small biopsies and the need to screen more number of biomarkers, the use of a single all-inclusive test is preferable over multiple consecutive assays. To meet high-quality diagnostics standards, we optimized and clinically validated WGS sample and data processing procedures, resulting in a technical success rate of 95.6% for fresh-frozen samples with sufficient (≥20%) tumor content. Independent validation of identified biomarkers against commonly used diagnostic assays showed a high sensitivity (recall; 98.5%) and precision (positive predictive value; 97.8%) for detection of somatic single-nucleotide variants and insertions and deletions (across 22 genes), and high concordance for detection of gene amplification (97.0%; EGFR and MET) as well as somatic complete loss (100%; CDKN2A/p16). Gene fusion analysis showed a concordance of 91.3% between DNA-based WGS and an orthogonal RNA-based gene fusion assay. Microsatellite (in)stability assessment showed a sensitivity of 100% with a precision of 94%, and virus detection (human papillomavirus), an accuracy of 100% compared with standard testing. In conclusion, whole genome sequencing has a >95% sensitivity and precision compared with routinely used DNA techniques in diagnostics, and all relevant mutation types can be detected reliably in a single assay., (Copyright © 2021 Association for Molecular Pathology and American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

Lipid analysis is a powerful tool that can elucidate the pathogenic roles of lipids in metabolic diseases, and facilitate the development of potential biomarkers. Lipid analysis by large-scale lipidomics requires a high-speed and high-throughput analytical platform. In the present study, a high-speed analytical method for lipid analysis using nanoflow ultrahigh-performance liquid chromatography-electrospray ionisation-tandem mass spectrometry (nUHPLC-ESI-MS/MS) was optimised by investigating the effects of column flow rate, pump flow rate, dwell time, initial binary mobile phase composition, and gradient duration on the separation efficiency of standard lipid mixtures. The minimum gradient time for high-speed lipid separation was determined by examining the time-based separation efficiency and spectral overlap of isobaric lipid species during selected reaction monitoring-based quantification of sphingomyelin and a second isotope of phosphatidylcholine, which differ in molecular weight by only 1 Da. Finally, the optimised nUHPLC-ESI-MS/MS method was applied to analyse 200 plasma samples from patients with liver, gastric, lung, and colorectal cancer to evaluate its performance by measuring previously identified candidate lipid biomarkers. About 73% of the reported marker candidates (6 out of 7 in liver, 5/9 in gastric, 4/6 in lung, and 6/7 in colorectal cancer) could be assigned using the optimised method, supporting its use for high-throughput lipid analysis., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Diagnosis of malignant biliary obstruction is complicated and lacks accuracy. Exosomes may be secreted by malignant tumors; intact miRNAs from exosomes might serve as potential biomarkers for the disease., Aim: To identify exosomal microRNAs in human bile among benign and malignant biliary obstructions., Methods: Bile samples were collected from patients undergoing therapeutic endoscopic retrograde cholangiopancreatography for biliary obstruction. Exosome microRNAs were determined by RNA-sequencing in the discovery cohort, which comprising benign (n = 5) cases and malignant biliary obstruction (n = 5) cases. Then, the diagnostic performance of the two up-regulated microRNAs (mir-483-5p and mir-126-3p) of bile exosomes was verified by analysis of 82 patients with a diagnosis of malignant (n=37) or nonmalignant (n=45) biliary obstruction., Results: In both cohorts, the expressions of mir-483-5p and mir-126-3p were significantly higher in bile exosomes samples from patients with malignant biliary obstructions than controls. In the verification cohort, the two miRNAs can distinguished the benign and malignant groups with high diagnostic accuracy and specificity; the diagnostic values of the two microRNAs were better than serum carbohydrate antigen 19-9 (CA19-9), area under the curve (AUC) were 0.81 and 0.74., Conclusion: The expression of exosomal mir-483-5p and mir-126-3p in the bile samples discriminates between patients with malignant and nonmalignant biliary obstructions., Clinical Trial Registration No: NCT03102268., Competing Interests: Declaration of Competing Interest All of the authors have no conflict of interest., (Copyright © 2020 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Background: Hyponatremia, the most common electrolyte disorder, has been reported to be related to increased mortality. However, the association between hyponatremia and prognoses remains unclear in patients with nutrition support team (NST) intervention. This study aimed to determine the prevalence of abnormal serum sodium levels, its relation to patient data, and the impact of hyponatremia on prognosis., Methods: Patients who received nutrition support at Tokushima University Hospital for the first time and whose serum sodium levels were measured at the start of NST intervention were enrolled. Patients were classified into three groups according to their serum Na levels at the start of NST intervention: hyponatremia group, normonatremia group, and hypernatremia group., Results: In the hyponatremia group compared to the normonatremia group, body weight and body mass index were significantly lower. C-reactive protein levels and urea nitrogen/creatinine ratios were significantly higher. Meanwhile, there was no significant difference in the estimated glomerular filtration rate among the groups. The prevalence of malnutrition and anemia were the highest in the hyponatremia group. The 3-year survival rate was approximately 45% in the hyponatremia group, which was the lowest of all three groups. The mortality risk ratio of the hyponatremia group to the normonatremia group was 2.29., Conclusions: Hyponatremia in NST intervention patients is an independent prognostic predictor. Therefore, adding an assessment of serum sodium at the beginning of NST intervention can identify patients at high risk at an early stage and may improve the quality of NST activity., (Copyright © 2020 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.)

Venous thromboembolism (VTE) is a common complication in patients with cancer. The risk of emergent VTE is four- to seven-fold higher in cancer patients compared to non-cancer patients. Although the therapeutic armamentarium for cancer-associated VTE has been recently implemented, anticoagulant treatment remains challenging because of the increased risk of recurrent VTE and bleeding. Several international societies and expert panels released clinical practice guidelines on VTE treatment which are mostly focused on the general cancer population. Nevertheless, recommendations for the management of VTE in patients with peculiar clinical presentations are inconsistent and remain elusive due to the lack of pertinent evidence. The challenging clinical scenarios include, among others, patients with thrombocytopenia, renal impairment, gastrointestinal cancer, primary or metastatic brain cancer, distal thrombosis of the lower extremities, catheter-related VTE, splanchnic thrombosis, incidental VTE, extreme body weight, recurrent VTE during treatment, as well as the optimal duration of anticoagulant treatment in patients with active disease who have received 3 to 6 months of anticoagulation. Herein, we present a critical overview on VTE management in these challenging clinical settings, discuss potential approaches, and include some calls to action for future clinical research., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Research reporting plasma micronutrient status and its impact on clinical outcomes in paediatric cancer is scarce. Therefore, we investigated the prevalence of plasma micronutrient abnormalities and their impact on clinical outcomes and treatment complications., Methods: A multicentre prospective-cohort study of children aged <18 years diagnosed with cancer was performed between Aug 2010-Jan 2014. Clinical and nutritional data were collected at diagnosis, 3, 6, 9, 12 and 18 months. Micronutrient status was established using in-house laboratory references (vitamin B12, vitamin A and Vitamin E/Ch) and aged adjusted Z-scores (Mg, Se, Zn and Cu) generated from a cohort of healthy Scottish children. Clinical outcomes were classified as "event free survival (EFS)" or "event" (relapse, death, new metastasis or becoming palliative) and treatment complications. Descriptive statistics, logistic regression and multilevel analysis were performed., Results: Eighty-two patients [median (IQR) 3.9 (1.9-8.8) years, 56% males] were recruited. Of these, 72 (88%) samples were available, 74% (53/72) patients had micronutrient abnormalities at baseline; deficiencies (25%, 18/72), excesses (19%, 14/72) and a combination of both (29%, 21/72), which continued for 18 months. Vitamin A deficiency (15%, 3/20) and excess (50%, 10/20) were most prevalent at 18 months, whilst vitamin E/Cholesterol and vitamin B12 were mostly within the normal range. Prevalence of Zn deficiency at diagnosis was 36% (16/44 adjusted for CRP), which remained at these levels throughout the study. Reduction in each selenium concentration unit increased the odds of an event by 2% (OR 0.02) and lower Se predicted higher complications at diagnosis [β (-1.2); t (-2.1); 95% CI (-2.9 - (-0.04)); p = 0.04], 3 months [β (-3.9); t (-4.2); 95% CI (-5.57 - (-2.02)); p < 0.001] and 12 months [β (-2.3); t (-2.4); 95% CI (-4.10 - (-0.34)); p = 0.02]., Conclusions: Given the prevalence of micronutrient abnormalities and the negative impact of low selenium on clinical outcome, micronutrient status should be assessed and monitored in paediatric cancer patients. Larger multicentre population based studies and clinical trials are now warranted., (Copyright © 2021 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Background & Aims: Arachidonic acid (AA) is metabolized by cyclooxygenases and lipoxygenases to pro-inflammatory eicosanoids, which according to experimental research modulate tumor cell proliferation, differentiation, and apoptosis. We employed the Mendelian randomization design to test the hypothesis that higher plasma phospholipid AA concentrations are associated with increased risk of 10 site-specific cancers., Methods: Two genetic variants associated with plasma phospholipid concentrations of AA (rs174547 in FADS1 [P = 3.0 × 10 -971 ] and rs16966952 in PDXDC1 [P = 2.4 × 10 -10 ]) in the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium were used as genetic instruments. The associations of those variants with cancer were taken from the UK Biobank (n = 367,643), FinnGen consortium (n = 135,638), International Lung Cancer Consortium (n = 27,209), Prostate Cancer Association Group to Investigate Cancer Associated Alterations in the Genome consortium (n = 140,254), Breast Cancer Association Consortium (n = 228,951), Ovarian Cancer Association Consortium (n = 66,450), and BioBank Japan (n = 212,453)., Results: Higher genetically predicted plasma phospholipid AA concentrations were associated with increased risk of colorectal and lung cancer. Results were consistent across data sources and variants. The combined odds ratios per standard deviation increase of AA concentrations were 1.08 (95% CI 1.05-1.11; P = 6.3 × 10 -8 ) for colorectal cancer and 1.07 (95%CI 1.05-1.10; P = 3.5 × 10 -7 ) for lung cancer. Genetically predicted AA concentrations had a suggestive positive association with esophageal cancer (odds ratio 1.09; 95% CI 1.02-1.17; P = 0.016) but were not associated with cancers of the stomach, pancreas, bladder, prostate, breast, uterus, or ovary., Conclusion: These results indicate that AA may be implicated in the development of colorectal and lung cancer and possibly esophageal cancer. Treatments with plasma AA-lowering properties should be evaluated for clinical benefit., Competing Interests: Conflicts of interest The authors declare that they have no competing interests., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Accumulating evidence arising from numerous clinical studies indicate that assembled and functional 20S proteasome complexes circulate freely in plasma. Elevated levels of this core proteolytic complex have been found in the plasma of patients suffering from blood, skin and solid cancers, autoimmune disorders, trauma and sepsis. Moreover, in various diseases, there is a positive correlation between circulating 20S proteasome (c20S) levels and treatment efficacy and survival rates, suggesting the involvement of this under-studied c20S complex in pathophysiology. However, many aspects of this system remain enigmatic, as we still do not know the origin, biological role or mechanisms of extracellular transport and regulation of c20S proteasomes. In this review, we provide an overview of the current understanding of the c20S proteasome system and discuss the remaining gaps in knowledge., (Copyright © 2020 Elsevier B.V. All rights reserved.)

The extracted miR-21 and miR-155 from the plasma of clinical samples were targeted by non-crosslinking hybridization of Au-nanoprobes without the need for biomarker amplification. Thirty samples, including those suspected to cancer and chemotherapy-treated samples, were analyzed. An increase in the concentration of target biomarkers caused a blue-shift in the visible spectrum of nanoprobes. Using magnesium chloride, the change in the color of nanoprobes was shown to be dependent on time besides intensity. Samples with high averages of intensity needed less time for colorimetric differentiation than those with low average intensity. Au-nanoprobe-21 was turned to purple-gray in clinical specimens of stomach, colon, breast, esophagus, sarcoma, diaphragm, prostate, bladder, and lung while Au-nanoprobe-155 appeared as light purple-gray in colon, breast, lung, diaphragm and esophagus samples. The LOD was measured as 5 ng μL -1 of targeted biomarkers. The developed nano-biosensing method could propose a point-of-care approach for cancer prognosis and diagnosis, facilitating targeted therapeutics., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Our understanding of vitamin D has improved considerably in recent years. The role of vitamin D in preventing osteoporotic fractures is now well-established. However, an important controversy has emerged in the last decade concerning the effects of the active form of vitamin D (1,25-dihydroxy-vitamin D) on tissues other than bone (non-classical effects). The demonstration that the vitamin D receptor (VDR) is ubiquitously, expressed combined with increasing observational data supporting a relationship between the level of 25-hydroxy-vitamin D in the serum and chronic metabolic disorders, cardiovascular disease and neoplasms, have led to its redefinition as a steroid hormone and the proposal of its use in preventing and/or treating those diseases. This article is an update on the different non-bone or non-classical effects of "vitamin-hormone D", and its potential preventive or therapeutic role in certain diseases, however, this review is not exhaustive. The different modalities of substitution or supplementation proposed in France by the Groupe de Recherche et d'Information sur les Ostéoporoses (GRIO) are also summarised., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

Background: Cancer patients are at increased risk of death from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Cancer and its treatment affect many haematological and biochemical parameters, therefore we analysed these prior to and during coronavirus disease 2019 (COVID-19) and correlated them with outcome., Patients and Methods: Consecutive patients with cancer testing positive for SARS-CoV-2 in centres throughout the United Kingdom were identified and entered into a database following local governance approval. Clinical and longitudinal laboratory data were extracted from patient records. Data were analysed using Mann-Whitney U test, Fisher's exact test, Wilcoxon signed rank test, logistic regression, or linear regression for outcomes. Hierarchical clustering of heatmaps was performed using Ward's method., Results: In total, 302 patients were included in three cohorts: Manchester (n = 67), Liverpool (n = 62), and UK (n = 173). In the entire cohort (N = 302), median age was 69 (range 19-93 years), including 163 males and 139 females; of these, 216 were diagnosed with a solid tumour and 86 with a haematological cancer. Preinfection lymphopaenia, neutropaenia and lactate dehydrogenase (LDH) were not associated with oxygen requirement (O 2 ) or death. Lymphocyte count (P < 0.001), platelet count (P = 0.03), LDH (P < 0.0001) and albumin (P < 0.0001) significantly changed from preinfection to during infection. High rather than low neutrophils at day 0 (P = 0.007), higher maximal neutrophils during COVID-19 (P = 0.026) and higher neutrophil-to-lymphocyte ratio (NLR; P = 0.01) were associated with death. In multivariable analysis, age (P = 0.002), haematological cancer (P = 0.034), C-reactive protein (P = 0.004), NLR (P = 0.036) and albumin (P = 0.02) at day 0 were significant predictors of death. In the Manchester/Liverpool cohort 30 patients have restarted therapy following COVID-19, with no additional complications requiring readmission., Conclusion: Preinfection biochemical/haematological parameters were not associated with worse outcome in cancer patients. Restarting treatment following COVID-19 was not associated with additional complications. Neutropaenia due to cancer/treatment is not associated with COVID-19 mortality. Cancer therapy, particularly in patients with solid tumours, need not be delayed or omitted due to concerns that treatment itself increases COVID-19 severity., Competing Interests: Disclosure RJL speaker fees BMS and Astrazeneca, MR honoraria from Astellas Pharma, speaker fees MSD and Servier. CW consultancy and speaker fees Pfizer, Amgen, Novartis, AA conference fee Merck, spouse shares in Astrazeneca. TR financial support to attend educational workshops from Amgen and Daiichi-Sankyo. JT is now working at Astra Zeneca. CD, outside of this scope of work, has received research funding from AstraZeneca, Astex Pharmaceuticals, Bioven, Amgen, Carrick Therapeutics, Merck AG, Taiho Oncology, Clearbridge Biomedics, Angle PLC, Menarini Diagnostics, GSK, Bayer, Boehringer Ingelheim, Roche, BMS, Novartis, Celgene, Thermofisher. CD is on advisory boards for, and has received consultancy fees/honoraria from, AstraZeneca, Biocartis and Merck KGaA. The remaining authors have no conflicts of interest to declare., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Exosomes, microvesicles derived from the nuclear endosome and plasma membrane, can be released into the extracellular environment to act as mediators between the cell membrane and cytoplasmic proteins, lipids, or RNA. Exosomes are considered effective carriers of intercellular signals in prokaryotes and eukaryotes, because of their ability to efficiently transfer proteins, lipids, and nucleic acids between cellular compartments. Since the 2007 discovery that exosomes carry bioactive substances, exosomes have been intensively researched. In various physiological and pathological processes, exosomes play important biological roles by specifically combining with receptor cells and transmitting information. Their stable biological characteristics, diversity of contents, non-invasiveness path for introducing signaling molecules, and ability for rapid detection make exosomes a promising clinical diagnostic marker for potentially many pathological conditions, including cancers. Exosomes are not only considered biomarkers and prognostic disease factors, but also have potential as gene carriers and drug delivery vectors, and have important clinical significance and application potential in the fields of cancer diagnosis, prognosis, and treatment., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Monoclonal antibodies that inhibit the programmed cell death protein 1 axis (anti-PD-1/PD-L1) are part of a new pharmacological strategy aimed at reinforcing the immune response to cancer. Despite the success in several cancer types, a significant percentage of patients do not benefit from treatment with these drugs due to intrinsic or acquired resistance or the occurrence of immune-related adverse reactions. Assessment of PD-L1 expression in tumor tissues is currently used to predict drug response in the clinics; however, there is a growing interest in identifying blood-based biomarkers that, owing to the minimally-invasive nature, can allow a dynamic monitoring of drug response in daily clinical practice. In the current review article, we discuss whether the assessment of PD-L1 mRNA and protein levels in circulating extracellular vesicles may have the potential to predict the likelihood of tumor response to anti-PD-1/PD-L1 antibodies., (Copyright © 2020. Published by Elsevier B.V.)

Early cancer detection is critical for effective treatment. N-NOSE (Nematode-NOSE) is a simple, inexpensive, and highly sensitive cancer screening method based on the chemotaxis of the nematode Caenorhabditis elegans, which shows evasive action from the urine of healthy individuals while being attracted to the urine of cancer patients. Initially, N-NOSE relied on chemotaxis indexes obtained with 10-fold dilutions of urine samples. However, cancer tissue size and concentrations of cancer odors differ among cancer patients. In this study, we examined the accuracy improvement of N-NOSE method by using two types of dilutions, 10-fold and 100-fold. We have conducted N-NOSE tests with urine samples from 32 cancer patients (esophageal, gastric, colorectal, gallbladder, cholangiocarcinoma, breast, malignant lymphoma, and acute myeloid leukemia) along with 143 healthy subjects. Our data showed a significant difference in the N-NOSE at 10-fold dilution between the two groups (p < 0.0001), with an area under the ROC curve (AUC) of 0.9188 based on receiver operating characteristic (ROC) analysis. N-NOSE index at 100-fold dilutions was also significantly different between the two groups (p < 0.0001), with an AUC of 0.9032 based on ROC analysis. In this clinical study, we further improve N-NOSE with a combined method of two dilutions (10-fold and 100-fold) of urine samples, which results in a markedly improvement in cancer detection sensitivity of 87.5%. N-NOSE sensitivity improvement was significantly high even for early-stage cancer detection, which is in stark contrast with the sensitivity of detection using blood tumor markers (CEA, CA19-9 and CA15-3). These results strongly suggest that the N-NOSE test by this new combined method strikes a good balance between sensitivity and specificity., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background & Aims: Systemic inflammation has been reported as a new predictor for cancer outcomes. This study aimed i) to identify the neutrophil to lymphocytes ratio (NLR) cut-off point that best predicts sarcopenia and ii) to verify the association between NLR and sarcopenia risk in hospitalized cancer patients., Methods: A cross-sectional study enrolled a total of 123 hospitalized cancer patients receiving chemotherapy and/or undergoing surgery. Systemic inflammation was assessed as revealed by circulating levels of C-reactive protein, neutrophils, platelet, and by calculating platelet-lymphocytes ratio (PLR) and NLR. Sarcopenia risk was assessed using the Strength, Assistance for walking, Rise from a chair, Climb stairs, and Falls (SARC-F; score≥4 identifies sarcopenia risk). ROC curve were used to identify the best NLR cut-off value which predicts sarcopenia risk. Differences between groups were tested using the T Student, Mann-Whitney, or Chi-Square tests. Logistic regression analyses were done to assess the association between NLR and sarcopenia risk., Results: ROC curve revealed that the best cut-off point to predict sarcopenia risk was NLR ≥6.5 (sensitivity of 45% and specificity of 81%). Those with NLR ≥6.5 presented higher C-reactive protein, neutrophils, platelet-lymphocytes ratio (PLR), and SARC-F than NLR <6.5 group. A negative correlation was found between NLR and gait speed (r = -0.48, p = 0.0001), handgrip strength (r = -0.29, p = 0.002), arm circumference (r = -0.29, p = 0.002) and calf circumference (r = -0.28, p = 0.003). Those with increased NLR values were associated with high sarcopenia risk in crude model, as well as if adjusted by smoking, alcohol intake, and sex (OR:1.19 [95%CI:1.03-1.37], p = 0.013) or by BMI (OR:1.20 [95%CI:1.05-1.38], p = 0.006)., Conclusion: In hospitalized cancer patients, systemic inflammation measured by NLR was associated with increased sarcopenia risk., Competing Interests: Conflict of interest None declared., (Copyright © 2020 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Systemic and organ-confined inflammation has been associated with cancer development and progression. Resistin, initially described as an adipocyte-derived cytokine in mice, is mostly expressed by the macrophages in humans. It has potent pro-inflammatory properties, and its elevated serum levels are detected in cancer patients. Aberrant expression of resistin receptors is also reported in several malignancies and associated with aggressive clinicopathological features. Several lines of evidence demonstrate that resistin, acting through its different receptors, promotes tumor growth, metastasis, and chemoresistance by influencing a variety of cellular phenotypes as well as by modulating the tumor microenvironment. Racially disparate expression of resistin has also attracted much interest, considering prevalent cancer health disparities. This review discusses the aberrant expression of resistin and its receptors, its diverse downstream signaling and impact on tumor growth, metastasis, angiogenesis, and therapy resistance to support its clinical exploitation in biomarker and therapeutic development., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Purpose: The purpose of the study is to quantitatively assess the association between C-reactive protein (CRP) and all-cause, cardiovascular disease (CVD), and cancer mortality; a dose-response meta-analysis was performed on data from cohort studies in general population., Methods: The published relevant articles were searched for in PubMed, Web of Science, and Embase until September 21, 2019. The pooled relative risk (RR) was estimated by random effects of generalized least square regression models. The dose-response relationship was modeled using restricted cubic splines., Results: Twenty-two articles were screened for the meta-analysis. Compared with the low CRP group, the pooled RR in the moderate CRP group was 1.30 (95% confidence interval (CI), 1.20-1.41) for all-cause mortality and 1.43 (95% CI, 1.22-1.68) for CVD mortality; the pooled RR in the high CRP group was 1.75 (95% CI, 1.59-1.92) for all-cause mortality, 2.02 (95% CI, 1.70-2.41) for CVD mortality, and 1.32 (95% CI, 1.21-1.45) for cancer mortality., Conclusions: This meta-analysis demonstrated the relationships between CRP and mortality were nonlinear for all-cause and CVD mortality and were linear for cancer and noncardiovascular mortality., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: - The management of venous thromboembolism (VTE) is particularly challenging in patients with cancer who undergo complex treatment protocols. Cancer patients often have comorbidities which may affect the efficacy and safety of anticoagulant treatments. Coordinated multidisciplinary management of these complex cases can help optimize delivery of individualized anticoagulant treatment., Aims: - To describe the multidisciplinary team meeting (MDTM) for the management of VTE in cancer patients at our institution and to document outcomes in these patients., Methods: - Bi-monthly MDTMs attended by different physicians and nurses were established at Saint-Louis Hospital in 2008. We performed a retrospective analysis of all cases discussed between September 2008 and January 2018., Results: - Over a 10-year period, 520 patients were discussed a total of 551 times. Their mean age was 63 years with 278 (53%) women. The most frequent primary cancer sites were breast (23%), genitourinary (21 %), hematological (20%), digestive (15%), and lung (9%). Fifty-two percent of patients had metastatic cancer, and 54% of them were receiving chemotherapy. The optimal treatment for pulmonary embolism (17%), deep vein thrombosis (16%), catheter-related thrombosis (20%) or combined events (46%) was discussed. Twenty-three patients (4.4%) were discussed for one VTE recurrence and 4 (0.8%) for 2 recurrences., Conclusions: - A dedicated MDTM for the management of VTE in cancer patients allows to discuss a wide range of clinical scenarios and contributes to optimal adherence to evidence-based clinical practices guidelines. The MDTM evaluation was successfully carried out within a short time-frame of VTE diagnosis and helped optimize individualized treatment plans., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

Venous thromboembolism (VTE) is a common complication in patients with cancer and portends a poor prognosis. Our understanding of the underlying pathophysiology of VTE in cancer has advanced since Trousseau first described hypercoagulability in patients with malignancy and Virchow described his famous triad of thrombosis formation. Malignancy itself induces a thrombophilic state by increasing the risk of venous stasis, endothelial injury and an imbalance of pro and anti-thrombotic factors leading to a hypercoaguable state. Additional insults to this thrombotic balance are introduced by patient-specific, treatment related and tumor-specific factors. The importance of understanding the factors associated with increased thrombosis in cancer is paramount in order to adequately identify patients who will benefit from thromboprophylaxis., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

Cancer associated thrombosis (CAT) has been demonstrated a long time ago and is a frequent comorbid condition. Some risk factors are well established and related to the treatment of cancer: surgery, chemotherapy, radiation therapy, indwelling catheters. Other risk factors depend on tumour type and patient presentation, in particular pancreatic and brain cancer, bed resting and previous venous thrombosis. With the advances in cancer treatment and care, patients with cancer live longer and experience various therapies, sometimes during a long time. There is a need to better define the incidence and prevalence of CAT in the light of new therapeutic strategies and patient survival. This article focuses on the description of incidence and prevalence of CAT in the literature and on the description of risk factors, traditional but also emerging ones., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

Cancer-associated thrombosis (CAT) is the second leading cause of death in cancer patients after tumor progression. The treatment of CAT is challenging because of a high risk of VTE recurrence, a high risk of bleeding, common presence of comorbidities, poly-medication, and potential drug-drug interactions (DDI). Since 2018, direct oral anticoagulants (DOACs) represent a promising therapeutic alternative and have been recently included into the 2019 update of the International Initiative on Thrombosis and Cancer (ITAC-CME) clinical practice guidelines for management of CAT. However, pharmacokinetic studies suggest that concomitant treatment with P-gp or CYP3A4 inhibitors will result in an increased exposure to rivaroxaban and apixaban, but the clinical relevance of these studies is unknown. In addition, there is an important inter-individual variability in drug absorption, distribution, metabolism and elimination, even more in cancer patients. Overall, the risk of pharmacokinetic DDI should be estimated based on several individual (patient age, renal and liver function, number of comedications) and diseases-related factors, including inflammation, sarcopenia, and low body weight. In this context, DDI with clinical implications could be expected with anti-neoplastic agents or supportive care treatments, especially with drugs known to be moderate or strong inhibitors/inducers of CYP3A4 and P-gp. Consequently, in the presence of potential DDIs through CYP3A4, and/or P-gp, LMWHs remain the first-line anticoagulant of choice for the long-term treatment of CAT. Multidisciplinary consultation meetings and therapeutic patient education should be emphasized in the complex management of CAT., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

Venous thromboembolism (VTE) is a common complication among patients with cancer, associated with significant higher rate of mortality and morbidity. Low-molecular-weight heparin (LMWH) as a single therapeutic is considered as the standard of care for the treatment of acute cancer-associated thrombosis for many years, showing a significant 40% reduction of recurrent VTE (RR: 0.58; 95% CI, 0.43 - 0.77) without a significant increase of major bleeding complications compared to VKA (RR: 1.09; 95% CI 0.55 - 2.12). Based on results analysis studies only including patients with proximal DVT or PE the risk of recurrent VTE was similar in the DOAC and the LMWH (RR 0.68; 95% CI, 0.39 - 1.17) groups, without significantively increasing the risk of either major bleeding (RR = 1.32; 95% CI 0.7 - 2.47) or CRNMB (RR 1.6; 95% 0.99 - 2.6). Compared with LMWH, the risk of major bleeding and clinically relevant-non major bleeding was higher, although non-significantly, with DOACs than with LMWH, underlying that DOACs should be avoided in patients at high risk of bleeding. The higher risk of bleeding reported in DOACs-treated patients appears related to an excess of upper GI bleeding. In addition to GI cancer, other high-risk features associated with bleeding complications are an urothelial cancer, drug-drug interactions and use of anticancer drugs associated with GI toxicity. Overall, DOACs are an effective treatment option, and safe in most cancer patients with acute VTE. Nonetheless, DOACs should be used with caution in cancer patients at high risk for bleeding due to cancer site and stage per se or to cancer treatments., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

Background: Coronavirus disease in 2019 (COVID-19) caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has emerged as a global pandemic. Published data suggests that patients with a history of or active malignancy are at increased risk of infection and developing COVID-19 related complications. To date, the published data has analyzed the seroprevalence of COVID-19 infection in the general population, but not in cancer patients. Here we present the results of prevalence of IgG and IgM antibodies against SARS-CoV-2 in cancer patients from the University Hospital of Torrejón (Torrejón de Ardoz, Madrid, Spain)., Methods: SARS-CoV-2 IgG and IgM antibodies was assessed using a commercially available rapid test (Testsealabs® IgG/IgM Rapid Test Cassette) and collect the result from cancer outpatients who attended the medical oncology consult at University Hospital of Torrejón between June 1st and June 19th, 2020., Findings: We analyzed the serological test results of 229 cancer patients. We estimated an overall seroprevalence (IgG or IgM positive) of 31.4%. The probability of SARS-CoV-2 seropositivity was similar between men and women, type of treatment and cancer stage. The probability of seropositivity was significantly higher in cancer patients with pneumonia compared with cancer patients without pneumonia (Odds Ratio (OR) 7.65 [95% confidence interval (CI) 1,85-31,58])., Interpretation: Our results show a higher rate of SARS-CoV-2 antibodies in cancer patients than in the general population. The role of those antibodies in the immune response against the virus infection is unclear., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background and Aims: Cardiovascular diseases (CVDis) are leading causes of morbidity and mortality. Even after the introduction of pharmacological therapy to lower Cholesterol, there is still a residual risk that may be ascribed to remnant cholesterol (RC). We aimed, by analyzing two prospective cohort studies, to estimate the effect of RC on risk and hazard of cardiovascular deaths (CVDs), while accounting for competing risks such as cancer (CDs) and other-causes deaths (OCDs)., Methods and Results: Cohorts were enrolled in 1992 and 2005. Personal data history was recorded. A fasting venous blood sample was obtained, and RC was calculated at baseline. Cause of Death was coded by using ICD-10th version. Follow-up ended on December 31, 2017. Flexible parametric competing-risks models were applied, with age at death as time-axis. In total, 5729 subjects were enrolled. There were 861 (15.1%) deaths: 234 CVDs (27.2%), 245 CDs (28.5%), 271 OCDs (31.5%) and 111 unknown causes of death (12.8%). RC exposure was a strong risk factor only for CVDs (Risk 2.54, 95% Confidence Interval 1.21; 5.34; Trend 1.26 (1.00; 1.58) for ≥1.29 mmol/L)., Conclusions: RC is a strong independent risk factor for cardiovascular mortality. Competing risk analysis is demonstrably a useful tool to disentangle associations among different competing events with a common risk factor., (Copyright © 2020 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)