Search

Background: Liquid biopsy is considered a complementary and recently also an alternative method to surgical biopsy. It allows for the acquisition of valuable information regarding the potential presence of tumors, particularly through the analysis of circulating tumor DNA (ctDNA). CtDNA is a fraction of circulating free DNA (cfDNA) that can be extracted from various tissues, with blood being the most readily available., Results: To maximize the yield of plasma separation, specific Streck tubes are recommended for blood collection. The MagPurix CFC DNA Extraction Kit can be used for cfDNA extraction, and the TWIST Library Preparation protocol can be optimized for further analysis. Next-generation sequencing (NGS) can be employed to compare somatic and germline lineages, enabling the identification of somatic variants with a Variant Allele Frequency (VAF) of 5 % or higher, which are absent in the germline lineage., Conclusion: This analysis helps in the assessment of recurrence, analysis, and monitoring of cancer tissue., Competing Interests: Declaration of competing interest The authors of this scientific article often publish together, being part of the same group and/or scientific society. The scientific journal designated to publish this article has a specific policy to ensure the optimal handling of these situations. The journal’s policy ensures that the peer review process is kept independent by selecting reviewers independent of the authors of the article. All affiliations of the authors with private companies have been declared to make clear the position regarding the interests of these companies. The authors are affiliated with private companies for which there could be a possible conflict of interest. The authors state that the research was conducted in the absence of any commercial relationship that could be construed as a possible direct conflict of interest avoiding mention of any products or services sold by private companies related to the authors. The authors of this article are reported to be patents inventors., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Research on the link between blood cell traits and cancer risk has gained significant attention. Traditional epidemiological and cell biology studies, have identified correlations between blood traits and cancer risks. These findings are important as they suggest potential risk factors and biological mechanisms. However, these studies often can't confirm causality, pointing to the need for further investigation to understand these relationships better., Methods: Mendelian randomization (MR), utilizing single-nucleotide polymorphisms as instrumental variables, was employed to investigate blood cell trait causal effects on cancer risk. Thirty-six blood cell traits were analyzed, and their impact on 28 major cancer outcomes was assessed using data from the FinnGen cohort, with eight major cancer outcomes and 22 cancer subsets. Furthermore, 1,008 MR analyses were conducted, incorporating sensitivity analyses (weighted median, MR-Egger, and MR-PRESSO) to address potential pleiotropy and heterogeneity., Results: The analysis (data from 173,480 individuals primarily of European descent) revealed significant results. An increase in eosinophil count was associated with a reduced risk of colorectal malignancies (OR = 0.7702 per 1 SD higher level, 95% CI = 0.6852 to 0.8658; P = 1.22E-05). Similarly, an increase in total eosinophil and basophil count was linked to a decreased risk of colorectal malignancies (OR = 0.7798 per 1 SD higher level, 95% CI = 0.6904 to 0.8808; P = 6.30E-05). Elevated hematocrit (HCT) levels were associated with a reduced risk of ovarian cancer (OR = 0.5857 per 1 SD higher level, 95% CI = 0.4443 to 0.7721; P = 1.47E-04). No significant heterogeneity or horizontal pleiotropy was observed., Conclusions: Our study highlights the complex and context-dependent roles of blood cell traits in cancers., Competing Interests: Declarations. Ethics approval and consent to participate: This study does not require institutional review committee ethical approval because all data used are sourced from the FinnGen project ( https://www.finngen.fi/en ) and various GWAS studies. Both FinnGen and GWAS studies have received ethical approval from their respective local institutional review boards and ethics committees. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

N 6 -methyladenosine (m 6 A) modification is one of the most widespread RNA modifications in eukaryotes and is involved in cancer development and progression by regulating oncogene expression. Herein, a reticulated rolling circle amplification (RCA) cascade reaction was used to construct a novel electrochemical biosensor for ultrasensitive detection of m 6 A, employing ferrocene-tyramine (Fc-Tyr) molecules as electroactive probes. In this strategy, the RCA cascade reaction not only amplifies specific circular DNA in the designed template to reduce the binding with similar nucleic acid sequences but also generates a long ssDNA through multiple repetitions to capture a large number of electrochemical signal probes and achieve the amplification of electrochemical biosensing signals. The developed biosensor demonstrated high selectivity and sensitivity toward m 6 A in the range of 0.5 pM-150 nM, with a detection limit of 14.07 fM. Meanwhile, total RNA extracted from cell samples was analyzed for m 6 A expression levels using the developed biosensor and a commercial colorimetric immunoassay, the biosensor and immunoassay showed consistent results. In addition, m 6 A levels in clinical serum samples were assessed using the developed electrochemical biosensor, which showed that m 6 A expression was much lower in healthy individuals than in cancer patients, therefore the biosensor is promising for cancer typing. This study provides a new method for rapid and convenient tumor marker detection in clinical practice, as well as a new idea for sensitive detection of other biomolecules.

Objective: To investigate the association of serum creatinine-cystatin C ratio (Cr/CysC) with long-term all-cause mortality and cause-specific (cardiovascular and cancer) mortality among US general adults., Methods: This nationally representative cohort study included adults in the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2004. Participants were linked to National Death Index data from the survey date through December 31, 2019. Weighted Cox proportional hazards regression models were used to calculate hazard ratios and 95% confidence intervals (CIs), and restricted cubic splines and stratified analyses were also performed., Results: A total of 12,914 participants were included in this study (mean [SD] age, 45.3 [17.3] years; males, 48.9%). During a median follow-up of 17.9 years (maximum follow-up, 20.8 years), 3439 total deaths occurred, including 1098 cardiovascular deaths and 736 cancer deaths. Cumulative incidence curves revealed that increased Cr/CysC ratio had lower risk of all-cause (P < 0.001), cardiovascular (P < 0.001) and cancer (P < 0.001) mortality. Cox regression an Fine-Gray hazards models demonstrated that the multivariable-adjusted hazard ratios comparing the highest vs. lowest quartile of Cr/CysC ratio were 0.40 (95% CI, 0.34-0.47; P < 0.001) for all-cause mortality, 0.68 (95% CI, 0.52-0.88; P < 0.001) for cardiovascular mortality, and 0.51 (95% CI, 0.36-0.71; P < 0.001) for cancer mortality. Nonlinear association was observed for Cr/CysC ratio and all-cause mortality (P = 0.018 for nonlinearity), and linear associations were observed for Cr/CysC ratio and cardiovascular (P = 0.212 for nonlinearity) and cancer (P = 0.550 for nonlinearity) mortality. Besides, a series of sensitivity analyses ensured the robustness of the results., Conclusions: In this cohort of US adults, Cr/CysC ratio was negatively associated with all-cause, cardiovascular, and cancer mortality. Our study suggests that Cr/CysC ratio may serve as a simple and effective predictor of long-term health outcomes., Competing Interests: Declarations. Ethics approval and consent to participate: The NHANES protocols were approved by the NCHS Research Ethics Review Board (Protocol #98 − 12) ( https://www.cdc.gov/nchs/nhanes/irba98.htm ) and were consistent with the Declaration of Helsinki. Each participant signed the written informed consent. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Despite a growing body of research indicating a link between fasting glucose levels and mortality, the relationship between fasting glucose and all-cause and cancer mortality remains inconsistent. In this study, we used Cox regression and restricted cubic spline models to analyze the association and dose-response relationship between fasting plasma glucose levels and all-cause and cancer mortality in a retrospective cohort based on data from the 2015 health check-ups of residents in Quzhou City. After a mean follow-up of 5.31 years for 148,755 study participants, 10,345 deaths occurred, with an all-cause mortality density of 131.09/10,000 person-years, of which 2,845 were cancer deaths, with a cancer mortality density of 36.05/10,000 person-years. There was a "J" shaped dose-response relationship between fasting plasma glucose levels and all-cause and cancer mortality. Relative to normal fasting glucose (NFG), the risk of all-cause mortality (HRs and 95% CIs) in the impaired fasting glucose (IFG) and diabetes mellitus (DM) groups was 1.11 (1.06, 1.16) and 1.43 (1.35, 1.52), respectively, and the risk of cancer mortality in the DM group was 1.22 (1.09, 1.37). In this cohort study, we found that fasting plasma glucose levels were significantly associated with the risk of all-cause and cancer mortality., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Gao et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The relationship between the alkaline phosphatase-to-albumin ratio (APAR) and mortality remains unclear. This research looked into the association between APAR levels and cause-specific mortality in US adults. A cohort of 7561 participants from National Health and Nutrition Examination Survey (2005-2016) was analyzed, with mortality outcomes collected from National Death Index records. Cox proportional hazards models and restricted cubic spline (RCS) analysis were utilized to determine hazard ratio (HR) and reveal the nonlinear relationship between APAR levels and mortality. Inflection points were calculated using a recursive algorithm. Followed for an average 99.41 months, a total of 1048 deaths occurred, including 200 cancer deaths and 348 cardiovascular disease-related deaths. Following multivariate adjustment, significant associations were observed between APAR levels and increased all-cause (HR 1.50, 95% CI 1.28-1.75, P < .001) and cardiovascular disease (HR 1.39, 95% CI 1.06-1.82, P = .018) mortality. Furthermore, nonlinear correlations between APAR levels and all-cause and cancer mortality were revealed, characterized by an L-shaped pattern, with mortality rates stabilizing at 1.289 and 2.167, respectively. Participants with APAR levels above the inflection point exhibited a 29.2% increase in all-cause mortality risk per unit increase in APAR levels (HR 1.292, 95% CI 1.217-1.372, P < .001), and a 38.3% increase in cancer mortality risk (HR 1.383, 95% CI 1.199-1.596, P < .001). This study demonstrated nonlinear associations between APAR levels and all-cause and cancer mortality. Thresholds of 1.289 and 2.167 might serve as potential targets for APAR to reduce all-cause and cancer mortality, respectively. Our findings suggest that APAR can be a valuable prognostic tool for clinical mortality risk assessments, helping to identify individuals at higher risk. Nevertheless, these findings necessitate validation through large-scale clinical trials for further substantiation., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: The relationship between serum urea concentration and cancer in patients with metabolic syndrome (MetS) remains unclear. This study aimed to investigate the association between serum urea concentration and 16 site-specific cancers, overall cancer incidence, and cancer mortality in individuals with MetS., Methods: We analysed the data of 108,284 individuals with MetS obtained from the UK Biobank. The Cox proportional hazards model was used to determine the association between serum urea concentration at recruitment and cancer. The Benjamini-Hochberg correction was used to account for multiple comparisons., Results: Over the median follow-up period of 11.86 years, 18,548 new incident cases of cancer were documented. There were inverse associations of urea concentration with overall cancer incidence, and the incidence of oesophageal and lung cancers, with respective hazard ratios (95% confidence intervals) [HR (95% CI)] for the highest (Q4) vs lowest (Q1) urea quartiles of 0.95 (0.91-0.99), 0.68 (0.50-0.92), and 0.76 (0.64-0.90). However, high serum urea concentrations increased the male prostate cancer risk (HR 1.15; 95% CI 1.02-1.30). Although the Cox model indicated a protective effect of higher urea levels against stomach (HR 0.67; 95% CI 0.45-0.98; p = 0.040; FDR 0.120) and colorectal cancer (HR 0.86; 95% CI 0.74-0.99; p = 0.048; FDR 0.123), no strong evidence of association was found after applying the Benjamin-Hochberg correction. Moreover, across the median follow-up period of 13.77 years for cancer mortality outcome, 5034 cancer deaths were detected. An "L-shaped" nonlinear dose-response relationship between urea concentration and cancer mortality was discovered (p-nonlinear < 0.001), and the HR (95% CI) for urea concentration Q4 vs Q1 was 0.83 (0.77-0.91)., Conclusions: Serum urea concentration can be considered as a valuable biomarker for evaluating cancer risk in individuals with MetS, potentially contributing to personalised cancer screening and management strategies., Competing Interests: Declarations Ethics approval and consent to participate The UK Biobank was approved by the Research Ethics Committees of the Northwest Multi-Centre (reference no. 16/NW/0274). All the study participants signed an informed consent form. Consent for publication Not applicable. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Early indicators of metastatic cancer response to therapy are important for evaluating new drugs and stopping ineffective treatment. The RECIST guidelines based on repeat cancer imaging are widely adopted in clinical trials, are used to identify active regimens that may change practice, and contribute to regulatory approvals. However, these criteria do not provide insight before 6 to 12 weeks of treatment and typically require that patients have measurable disease. Recent data suggest that measuring on-treatment changes in the amount or proportion of ctDNA in peripheral blood plasma may accurately identify responding and nonresponding cancers at earlier time points. Over the past year, the RECIST working group has evaluated current evidence for plasma ctDNA kinetics as a treatment response biomarker in metastatic cancers and early endpoint in clinical trials to identify areas of focus for future research and validation. Here, we outline the requirement for large standardized trial datasets, greater scrutiny of optimal ctDNA collection time points and assay thresholds, and consideration of regulatory body guidelines and patient opinions. In particular, clinically meaningful changes in plasma ctDNA abundance are likely to differ by cancer type and therapy class and must be assessed before ctDNA can be considered a potential pan-cancer response evaluation biomarker. Despite the need for additional data, minimally invasive on-treatment ctDNA measurements hold promise to build upon existing response assessments such as RECIST and offer opportunities for developing novel early endpoints for modern clinical trials., (©2024 American Association for Cancer Research.)

The use of circulating tumour DNA (ctDNA) to profile mutational signatures represents a non-invasive opportunity for understanding cancer mutational processes. Here we present MisMatchFinder, a liquid biopsy approach for mutational signature detection using low-coverage whole-genome sequencing of ctDNA. Through analysis of 375 plasma samples across 9 cancers, we demonstrate that MisMatchFinder accurately infers single-base and doublet-base substitutions, as well as insertions and deletions to enhance the detection of ctDNA and clinically relevant mutational signatures., Competing Interests: Competing interests The authors declare the following competing interests: S.-J.D. is an advisory board member for Adela. The remaining authors declare no competing interests., (© 2024. The Author(s).)

Depression frequently comorbidities with cancer, adversely affecting survivors' quality of life. Liver dysfunction is also prevalent among cancer survivors. However, the association between these two conditions remains unclear. This study aimed to explore the relationship between depression and liver function biomarkers in US cancer survivors. A cross-sectional study was conducted utilizing data from the National Health and Nutrition Examination Survey (NHANES) 2005-2020. Cancer survivors were screened and depression was assessed using the Patient Health Questionnaire-9 (PHQ-9), and 18 liver function biomarkers were included. Survey-weighted generalized linear models with multiple covariables adjusted were employed to examine the associations between depression and liver function biomarkers. A total of 4118 cancer survivors were included, representing a weighted population of 21 501 237. After adjusted with age, gender, race, marital status, education level, family income-to-poverty ratio, and number of cancer types, 8 biomarkers demonstrated positive correlations with depression in cancer survivors, included alanine aminotransferase (ALT, OR = 1.007, 95% CI: 1.000 to 1.013), alkaline phosphatase (ALP, 1.006 [1.002, 1.010]), gamma glutamyl transferase (GGT, 1.004 [1.001, 1.007]), lactate dehydrogenase (LDH, 1.004 [1.000, 1.009]), total protein (TP, 1.040 [1.009, 1.072]), globulin (GLB, 1.060 [1.030, 1.091]), total cholesterol (TC) to high-density lipoprotein cholesterol (HDL-C) ratio (1.162 [1.050, 1.286]), and low-density lipoprotein cholesterol (LDL-C) to HDL-C ratio (1.243 [1.012, 1.526]); while 4 other biomarkers exhibited negative correlations, included HDL-C (0.988 [0.980, 0.997]), total bilirubin (TBi, 0.501 [0.284, 0.883]), aspartate aminotransferase (AST) to ALT ratio (0.588 [0.351, 0.986]), albumin (ALB) to GLB ratio (0.384 [0.229, 0.642]). Following sensitivity analysis, 5 biomarkers included LDH, HDL-C, TBi, AST/ALT and LDL-C/HDL-C lost their statistical significance for the association. This study identified certain associations between 7 liver function biomarkers and depression in US cancer survivors. Further research, particularly prospective longitudinal studies, is warranted to elucidate the causal relationships and explore the potential of improving liver function for the management of depression in cancer patients., Competing Interests: Declarations Competing interests The authors declare no competing interests. Ethics approval and consent to participate All the NHANES protocols were approved by the Ethics Review Board of U.S. National Center for Health Statistics, and written informed consents were obtained from all participants of NAHNES surveys., (© 2024. The Author(s).)

Purpose: HERALD/EPOC1806 was conducted as a multicenter phase II trial assessing trastuzumab deruxtecan (T-DXd) therapy for patients with human epidermal growth factor receptor 2 ( HER2 )-amplified progressive stage solid tumors detected by cell-free DNA (cfDNA) testing., Patients and Methods: Patients exhibited advanced solid tumors with HER2 amplification that was identified via next-generation sequencing of cfDNA testing, without the requirement for immunohistochemical HER2 testing. The studied group was administered T-DXd at 5.4 mg/kg once every 3 weeks until onset of disease progression or intolerable toxicity., Results: Overall, 4,734 patients underwent cfDNA testing from December 2019 to January 2022, and 252 demonstrated HER2 amplification. Finally, the study included 62 patients with 16 cancer types with a median baseline plasma HER2 copy number (CN) of 8.55 (range, 2.4-73.9). Confirmed overall response rate (ORR) by investigator assessment was 56.5% (95% CI, 43.3 to 69.0), thus showing a value beyond the 5% threshold. Responses were evaluated for 13 cancer types, including KRAS -mutant colorectal (1/3), PIK3CA -mutant endometrial (5/6), and tissue HER2-negative gastric (1/2) cancers. Plasma HER2 CN above versus below the baseline median value did not differ for impact response; however, clearance of HER2 amplification in cfDNA on cycle 2 day 1 had higher response values compared with persistence. Median progression-free survival and response duration were 7.0 (95% CI, 4.9 to 9.7) and 8.8 (95% CI, 5.8 to 11.2) months, respectively, with the majority of complications being mild to moderate. Interstitial lung diseases were identified in 16 (26%) patients, including 14 patients with grade 1 disease, one patient with grade 2 disease, and one patient with grade 3 disease., Conclusion: T-DXd treatment demonstrated high ORR with durable response in patients with advanced HER2 -amplified solid tumors determined with cfDNA testing.

Background: The major breakthrough in cancer therapy with immune checkpoint inhibitors (ICIs) has highlighted the important role of immune checkpoints in antitumoral immunity. However, most patients do not achieve durable responses, making biomarker research in this setting essential. CD27 is a well known costimulatory molecule, however the impact of its soluble form in ICI is poorly investigated. Therefore, we aimed at testing circulating concentrations of soluble CD27 (sCD27) and CD27 bound to extracellular vesicles (EVs) as potential biomarkers to predict response and overall survival (OS) in patients undergoing ICI., Methods: Serum and plasma levels of sCD27 were assessed by immunoassay in three patient cohorts (n = 187) with advanced solid malignancies including longitudinal samples (n = 126): a training (n = 84, 210 specimens, Aachen ICI) and validation cohort (n = 70, 70 specimens, Hamburg ICI), both treated with ICI therapy, and a second independent validation cohort (n = 33, 33 specimens, Hamburg non-ICI) undergoing systemic therapy without any ICI. In a subset (n = 36, 36 baseline and 108 longitudinal specimens), EV-bound CD27 from serum was measured, while EV characterization studies were conducted on a fourth cohort (n = 45)., Results: In the Aachen and Hamburg ICI cohorts, patients with lower circulating sCD27 levels before and during ICI therapy had a significantly longer progression-free survival (PFS) and OS compared to patients with higher levels, a finding that was confirmed by multivariate analysis (MVA) (Aachen ICI: p PFS  = 0.012, p OS  = 0.001; Hamburg ICI: p PFS  = 0.040, p OS  = 0.004) and after randomly splitting both cohorts into training and validation. This phenomenon was not observed in the Hamburg non-ICI cohort, providing a rationale for the predictive biomarker role of sCD27 in immune checkpoint blockade. Remarkably, EV-bound CD27 baseline levels and dynamics during ICI therapy also emerged as potent predictive biomarkers, acting however antagonistically to soluble sCD27, i.e. higher levels were associated with PFS and OS benefit. Combining both molecules ("multi-CD27" score) enhanced the predictive ability (HR PFS : 17.21 with p < 0.001, HR OS : 6.47 with p = 0.011)., Conclusion: Soluble and EV-bound CD27 appear to have opposing immunomodulatory functions and may represent easily measurable, non-invasive prognostic markers to predict response and survival in patients undergoing ICI therapy., (© 2024. The Author(s).)

Aims: Hypoalbuminemia can lead to underestimations of the true anion gap levels. There are few data on albumin-corrected serum anion gap (ACAG) status and mortality in the diabetes. The study aimed to examine the association between ACAG and all-cause, cardiovascular, and cancer mortality in type 2 diabetes (T2D) patients., Methods: Herein, 8,161 diabetic adults were included in the National Health and Nutrition Examination Survey (NHANES) 1999-2018. National Mortality Index (NDI) data were used for determining mortality outcomes through 31 December 2019. Cox proportional hazards models were used to estimate the risk of all-cause, cardiovascular, and cancer mortality. We conducted a mediation analysis using the counterfactual framework method to estimate how ACAG may be indirectly associated with increased mortality risk through mediators., Results: A total of 2,309 deaths were documented over 8,161 person-years of follow up, including 659 cardiovascular and 399 cancer deaths. In multivariate analyses, higher ACAG levels had a significant correlation with an increase in all-cause (HR, 1.58; 95% CI, 1.38-1.81; P=0.001), cardiovascular (HR, 1.34; 95% CI, 1.05-1.72; P=0.019), and cancer (HR, 1.41; 95% CI, 1.02-1.96; P=0.018) mortality rates than the controls. Results of the mediation analysis showed that altered levels of C-reactive protein and estimated glomerular filtration rate (eGFR) explained 7.867% and 7.669% of the relation between serum ACAG and all-cause mortality, respectively (all P<0.05). Total cholesterol and HbA1c mediated 15.402% and 14.303% of the associations with cardiovascular mortality, respectively (all P<0.05)., Conclusions: Higher ACAG levels were significantly associated with increased all-cause, cardiovascular, and cancer mortality. Researchers suggest that patients with T2D who control ACAG in a normal state may be at a lower risk of mortality., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Wang, Yang, Deng, Wu, He, Li, Dong, Zhang and Li.)

Background: Cell-free DNA (cfDNA) analysis offers an attractive noninvasive means of detecting and monitoring diseases. cfDNA cleavage patterns within a short range (e.g., 11 nucleotides) have been reported to correlate with cytosine-phosphate-guanine (CpG) methylation, allowing fragmentomics-based methylation analysis (FRAGMA). Here, we adopted FRAGMA to the extended region harboring multiple nucleosomes, termed FRAGMAXR., Methods: We profiled cfDNA nucleosomal patterns over the genomic regions from -800 to 800 bp surrounding differentially methylated CpG sites, harboring approximately 8 nucleosomes, referred to as CpG-associated cfDNA nucleosomal patterns. Such nucleosomal patterns were analyzed by FRAGMAXR in cancer patients and pregnant women., Results: We identified distinct cfDNA nucleosomal patterns around differentially methylated CpG sites. Compared with subjects without cancer, patients with hepatocellular carcinoma (HCC) showed reduced amplitude of nucleosomal patterns, with a gradual decrease over tumor stages. Nucleosomal patterns associated with differentially methylated CpG sites could be used to train a machine learning model, resulting in the detection of HCC patients with an area under the receiver operating characteristic curve of 0.93. We further demonstrated the feasibility of multicancer detection using a dataset comprising lung, breast, and ovarian cancers. The tissue-of-origin analysis of plasma cfDNA from pregnant women and cancer patients revealed that the placental DNA and tumoral DNA contributions deduced by FRAGMAXR correlated well with values measured using genetic variants (Pearson r: 0.85 and 0.94, respectively)., Conclusions: CpG-associated cfDNA nucleosomal patterns of cfDNA molecules are influenced by DNA methylation and might be useful for biomarker developments for cancer liquid biopsy and noninvasive prenatal testing., (© Association for Diagnostics & Laboratory Medicine 2024.)

Purpose: Pulse oximetry remote patient monitoring (RPM) post-hospital discharge increased during the COVID-19 pandemic as patients and providers sought to limit in-person encounters and provide more care in the home. However, there is limited evidence on the feasibility and appropriateness of pulse oximetry RPM in patients with cancer after hospital discharge., Methods and Materials: This feasibility study enrolled oncology patients discharged after an unexpected admission at the Memorial Sloan Kettering Cancer Center from October 2020 to July 2021. Patients were asked to measure their blood oxygen (O 2 ) level daily during the hours of 9 am-5 pm during a 10-day monitoring period posthospitalization. An automated system alerted clinicians to blood O 2 levels below 93.0%. We evaluated the feasibility (>50.0% of patients providing at least one measurement from home) and appropriateness (>50.0% of alerts leading to a clinically meaningful patient interaction) of pulse oximetry RPM., Results: Sixty-two patients were enrolled in the study, with 53.2% female patients and a median age of 68 years. The most prevalent malignancy was thoracic (62.9%). The feasibility metric was met, with 45 patients (72.6%, 45 of 62) providing blood O 2 levels at least once during the 10-day monitoring program. The appropriateness threshold was not met; of the 121 alerts, only 39.7% (48 alerts) was linked to a clinically meaningful interaction., Conclusion: This feasibility study showed that while patients with cancer were willing to measure blood O 2 levels at home, most alerts did not result in meaningful clinical interactions. There is a need for improved patient support systems and logistical infrastructure to support appropriate use of RPM at home.

Background: Detection of cancer at the early stage currently offers the only viable strategy for reducing disease-related morbidity and mortality. Various approaches for multi-cancer early detection are being explored, which largely rely on capturing signals from circulating analytes shed by tumors into the blood. The fact that biomarker concentrations are limiting in the early stages of cancer, however, compromises the accuracy of these tests. We, therefore, adopted an alternate approach that involved interrogation of the serum metabolome with machine learning-based data analytics. Here, we monitored for modulations in metabolite patterns that correlated with the presence or absence of cancer. Results obtained confirmed the efficacy of this approach by demonstrating that it could detect a total of 15 cancers in women with an average accuracy of about 99%., Aims: To further increase the scope of our test, we conducted an investigator-initiated clinical trial involving a total of 6445 study participants, which included both cancer patients and non-cancer volunteers. Our goal here was to maximize the number of cancers that could be detected, while also covering cancers in both females and males., Methods and Results: Metabolites extracted from individual serum samples were profiled by ultra-performance liquid chromatography coupled to a high-resolution mass spectrometer using an untargeted protocol. After processing, the data were analyzed by our cancer detection machine-learning algorithm to differentiate cancer from non-cancer samples. Results revealed that our test platform could indeed detect a total of 30 cancers, covering both females and males, with an average accuracy of ~98%. Importantly, the high detection accuracy remained invariant across all four stages of the cancers., Conclusion: Thus, our approach of integrating untargeted metabolomics with machine learning-powered data analytics offers a powerful strategy for early-stage multi-cancer detection with high accuracy., Trial Registration: Registration No: CTRI/2023/03/050316., (© 2024 The Author(s). Cancer Reports published by Wiley Periodicals LLC.)

Aims: This study investigated the association of postprandial plasma glucose (PPG) with cancer mortality using a general cohort of US adults., Materials and Methods: This cohort study included 14,860 US adults who attended the third National Health and Nutrition Examination Survey from 1988 to 1994, with mortality being followed up until December 31, 2019. The explanatory variable was the level of plasma glucose, including PPG with a fasting time of 0-3.9 h (PPG 0-3.9h ) and 4-7.9 h (PPG 4-7.9h ), plasma glucose with a fasting time ≥8 h (PG fasting ), and plasma glucose at 2 h after oral glucose tolerance test (PG 2hOGTT ). Plasma glucose-associated cancer mortality risk was assessed using Cox proportional hazard models., Results: A 1-natural-log-unit increase in PPG 4-7.9h was associated with a higher multivariate-adjusted risk for cancer mortality [hazard ratio (HR), 3.24; 95% confidence interval (CI), 1.50-7.00]. However, PPG 0-3.9h , PG fasting , PG 2hOGTT , haemoglobin A 1c , and insulin were not significantly associated with cancer mortality. The positive association of PPG 4-7.9h with cancer mortality remained in those without a prior diagnosis of cancer., Conclusions: High PPG 4-7.9h is associated with a higher cancer mortality risk in US adults. Lowering PPG 4-7.9h may reduce cancer mortality., (© 2024 John Wiley & Sons Ltd.)

Molecular targeted tyrosine kinase inhibitors (TKIs) have produced unprecedented treatment response in cancer therapy for patients harboring specific oncogenic mutations. While the TKIs are mostly well tolerated, they were reported to increase serum levels of creatine kinase (CK) and cause muscle metabolism-related toxicity. CK is an essential enzyme involved in cellular energy metabolism and muscle function. Elevated serum CK levels can arise from both physiological and pathological factors, as well as triggered by specific drug classes. The incidence of serum CK elevation induced by a few approved TKIs (brigatinib, binimetinib, cobimetinib-vemurafenib combination [Food and Drug Administration, United States]; aumolertinib, and sunvozertinib [only approved by National Medical Products Administration, China]) were over 35%. CK elevation-related symptoms include myopathy, myositis, inclusion body myositis (IBM), cardiotoxicity, rhabdomyolysis, rash, and acneiform dermatitis. High-level or severe symptomatic CK elevation may necessitate dose reduction and indirectly dampen TKI efficacy. This review presents an updated summary about the prevalence rate and recent research about mechanisms leading to TKI-induced serum CK elevation in cancer patients. The utility of monitoring serum CK levels for predicting TKI-induced adverse effects and their management will also be discussed., (© 2024 The Author(s). Clinical and Translational Science published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)

Superoxide dismutase (SOD) catalyzes the highly reactive superoxide anion to form hydrogen peroxide, which facilitates cell proliferation and death. We investigated whether red cell SOD (R-SOD) activity is associated with an increased risk of cancer in a Japanese general population. We prospectively analyzed data from 1,921 participants (800 men and 1,121 women; age, 58.7 ± 14.7 years) in a Hidaka cohort study. After a median follow-up period of 10.9 years, 160 participants had developed cancer. The Cox proportional hazards model was used to estimate quartile-specific HRs and 95% confidential intervals (CI) for cancer risk. After adjustment for potential cancer risk factors including age, sex, current smoking habit, alcohol use, physical activities, body mass index, plasma immunoreactive insulin, and non-high-density lipoprotein cholesterol levels, we found a significant association between R-SOD activity and an increased risk of cancer (HR, 1.61; 95% CI, 1.03-2.52; P = 0.037). In analyses conducted separately by sex, a significant association was found in men (HR, 2.49; 95% CI, 1.35-4.59; P = 0.003) but not women (HR, 1.46; 95% CI, 0.70-3.05; P = 0.320). After excluding participants who developed cancer within 5 years of the baseline survey, the association was more evident in men (HR, 4.64; 95% CI, 1.88-11.45; P = 0.001). We found no association with cancer risk in women (HR, 1.01; 95% CI, 0.39-2.65; P = 0.983). Increased R-SOD activities were associated with an increased risk of cancer, particularly in men in this population., Significance: Our study is the first to show that increased R-SOD activity is associated with a significantly higher cancer risk in men but not in women. Antioxidative enzymes such as SOD are essential for maintaining cellular redox balance. Their roles in cancer development and prevention are yet to be fully elucidated., (©2024 The Authors; Published by the American Association for Cancer Research.)

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: Unnecessary group and screens (G&S) can lead to unnecessary antibody investigations, use of technologist time, and laboratory resources., Local Problem: A baseline audit at our institution identified that 25% of G&S from the cancer center were unnecessary. We aimed to reduce the ratio of monthly G&S to CBC samples processed from the cancer center by 10% (from 0.034 to 0.031) by January 2024., Methods: This represents an interrupted time series design from November 2022 to January 2024. Using Plan Do Study Act (PDSA) cycles, we aimed to increase the use of an existing reflex testing system, termed "do not test." When this option is selected, the blood bank will only process the G&S sample if specific CBC criteria are met (e.g., hemoglobin <9.0 g/dL). Educational sessions increased awareness of this feature and sought feedback from end-users on its usability. With feedback, the design was updated to include a modifiable hemoglobin threshold for G&S testing, automatic re-selection of the "do not test" feature for future G&S orders, and aesthetic changes to make the feature more visible., Results: The percentage of samples with "do not test" selected increased from 7.2% to 63.0% (p < .0001) and the ratio of G&S to CBC specimens improved from 0.034 to 0.028, exceeding the target of 0.031. We noted an improvement in the appropriateness of G&S orders from 75% at baseline (n = 20) to 97.5% (n = 80) post intervention (p = .003)., Conclusions: We describe an effective strategy to improve G&S utilization at our institution's cancer center using a reflex testing system., (© 2024 The Author(s). Transfusion published by Wiley Periodicals LLC on behalf of AABB.)

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.)

Aims: Inflammation plays a crucial role in the interconnection between diabetes and cancer. Our study seeks to investigate the predictive value of inflammatory indices concerning overall survival (OS) among diabetic cancer patients., Methods: We analyzed data from the National Health and Nutrition Examination Survey between 1999 and 2020. Using four immune-related markers, we employed the log-rank method, multivariate Cox regression, and subgroup analysis to explore the predictive capacity of these markers for OS among adult individuals with diabetes and cancer., Results: Our study identified four systemic immune-inflammatory indices that demonstrated significant predictive potential for OS among diabetic cancer patients, namely systemic immune-inflammation index, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and lymphocyte-to-monocyte ratio (all p values < 0.05). Notably, these inflammatory biomarkers still maintain their predictive value after adjusting potential confounding factors. The analysis using restrictive cubic splines revealed significant non-linear relationships between inflammatory biomarkers and OS., Conclusion: The findings presented in this study underscore the potential of inflammatory markers as prognostic indicators and their crucial role in enhancing risk assessment for diabetic patients with cancer., (© 2024. Springer-Verlag Italia S.r.l., part of Springer Nature.)

The study investigated the relationship between serum proinflammatory cytokine levels, cholesterol metabolism, and clinical outcome in cancer patients undergoing immune checkpoint inhibitors (ICIs). Peripheral blood was collected before therapy from ICI-treated advanced cancer patients. We retrospectively assessed plasma total cholesterol (TC), ABCA1- and ABCG1-mediated cholesterol efflux (CE), passive diffusion (PD), cholesterol loading capacity (CLC), and serum IL-6, IL-10, and TNF-α. The association between blood cholesterol parameters and inflammatory cytokines and their effect on overall survival (OS), progression-free survival (PFS), and clinical benefit (CB) from ICIs were statistically assessed. Among 70 consecutively enrolled patients (nonsmall cell lung cancer: 94%; renal cell carcinoma: 6%), TC, CLC, and cholesterol PD resulted significantly higher in IL-6 low and IL-10 low cases ( P <0.05), whereas ABCA1-mediated CE was increased in IL-10 high patients ( P =0.018). Uni- and multivariable analysis revealed meaningfully longer OS and PFS in IL-6 low (HR 2.13 and 2.97, respectively) and IL-10 low (HR 3.17 and 2.62) groups. At univariate analysis all cholesterol-related indices significantly correlated with OS and PFS, whereas at multivariate only high PD was validated as a protection factor (OS, HR 0.75; PFS, HR 0.84). Finally, uni- and multivariable showed a statistically significant inverse association of CB with ABCG1-CE (OR 0.62), as with IL-6 (OR 0.13) and IL-10 (OR 0.10). In-depth characterization of the interplay between blood cholesterol metabolism and immune-inflammatory cytokines might provide novel insights into the complex relationship among cancer, inflammation, lipids profile, and response to immunotherapy., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

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.)

The red cell distribution width (RDW) is a standard variable reported in the complete blood count. It has been found to have a consistent relationship to life expectancy in older individuals, prognosis in patients with cardiovascular disease, outcome in those with hematological and non-hematological neoplasms and in a variety of medical circumstances such as non-cardiovascular or cancer related critical illness and postoperative outcome from various procedures. This report reviews some of the key medical publications establishing these relationships with RDW. The precise pathobiological processes that explain the predictive value of the RDW in this wide array of circumstances or why an alteration in erythropoiesis (exaggerated red cell size variation) occurs is uncertain. The possible role of inflammation has been one hypothesis considered, but not established., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Liquid biopsy demonstrates excellent potential in patient management by providing a minimally invasive and cost-effective approach to detecting and monitoring cancer, even at its early stages. Due to the complexity of liquid biopsy data, machine-learning techniques are increasingly gaining attention in sample analysis, especially for multidimensional data such as RNA expression profiles. Yet, there is no agreement in the community on which methods are the most effective or how to process the data. To circumvent this, we performed a large-scale study using various machine-learning techniques. First, we took a closer look at existing datasets and filtered out some patients to assert data collection quality. The final data collection included platelet RNA samples acquired from 1397 cancer patients (17 types of cancer) and 354 asymptomatic, presumed healthy, donors. Then, we assessed an array of different machine-learning models and techniques (e.g., feature selection of RNA transcripts) in pan-cancer detection and multiclass classification. Our results show that simple logistic regression performs the best, reaching a 68% cancer detection rate at a 99% specificity level, and multiclass classification accuracy of 79.38% when distinguishing between five cancer types. In summary, by revisiting classical machine-learning models, we have exceeded the previously used method by 5% and 9.65% in cancer detection and multiclass classification, respectively. To ease further research, we open-source our code and data processing pipelines (https://gitlab.com/jopekmaksym/improving-platelet-rna-based-diagnostics), which we hope will serve the community as a strong baseline., (© 2024 The Author(s). Molecular Oncology published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.)

Background: Vitamin D deficiency is linked to poor cancer outcomes but the impact of its consequence, elevated parathyroid hormone (PTH), remains understudied. PTH receptor activation influences cancer progression in vitro, yet the effect of elevated PTH on pediatric cancer survival is unexamined., Methods: This retrospective study examines associations between PTH, 25-OH vitamin D (25OHD), and event-free survival (EFS) and overall survival (OS) in patients with pediatric cancer. Laboratory data from 4,349 patients (0-18 years) at a tertiary pediatric cancer unit were analyzed for the highest PTH and lowest 25OHD levels at diagnosis and the following 5 years. Data on relapse, secondary malignancies, and mortality were stratified by PTH levels above/below the cohort median (47 pg/mL) and 25OHD levels ≤30 nmol/L. EFS and OS were analyzed and hazard ratios (HR) were calculated for the entire cohort and six cancer subgroups., Results: PTH and 25OHD values were available for 1,286 patients (731 male). Higher PTH associated with inferior EFS in primary malignant brain tumors [HR, 1.80 (1.19-2.72)], embryonal malignancies [HR, 2.20 (1.1-4.43)], and lymphatic malignancies [HR 1.98 (1.05-3.72)]. Vitamin D deficiency associated with inferior EFS in embryonal malignancies [HR 2.41 (1.24-4.68)]. In a multivariate Cox model, only higher PTH remained significant for inferior EFS., Conclusions: Elevated PTH may indicate adverse outcomes in certain pediatric cancers., Impact: This study identifies elevated parathyroid hormone as a potential marker for poor outcomes in patients with pediatric cancer, emphasizing the need for adequate vitamin D and calcium management., (©2024 The Authors; Published by the American Association for Cancer Research.)

Circulating tumor cells (CTCs) enumeration and molecular profiling hold promise in revolutionizing the management of solid tumors. Their understanding has evolved significantly over the past two decades, encompassing pivotal biological discoveries and clinical studies across various malignancies. While for some tumor types, such as breast, prostate, and colorectal cancer, CTCs are ready to enter clinical practice, for others, additional research is required. CTCs serve as versatile biomarkers, offering insights into tumor biology, metastatic progression, and treatment response. This review summarizes the latest advancements in CTC research and highlights future directions of investigation. Special attention is given to concurrent evaluations of CTCs and other circulating biomarkers, particularly circulating tumor DNA. Multi-analyte assessment holds the potential to unlock the full clinical capabilities of liquid biopsy. In conclusion, CTCs represent a transformative biomarker in precision oncology, offering extraordinary opportunities to translate scientific discoveries into tangible improvements in patient care., Competing Interests: Declaration of Competing Interest Singhal S. has received consulting fees from Oncohost. Fusco N. has received honoraria for consulting, advisory role, speaker bureau, travel, and/or research grants from Merck Sharp & Dohme (MSD), Merck, Novartis, AstraZeneca, Roche, Menarini, Daiichi Sankyo, GlaxoSmithKline (GSK), Gilead, Adicet Bio, Sysmex, Reply, Veracyte Inc., Sakura, Leica Biosystems, Lilly. Cristofanilli M reports personal fees from Lilly, Sermonix, Data Genomics, Foundation Medicine, Guardant Health, Celcuity, Iylon, and Ellipses and grants and personal fees from Pfizer, AZ and Menarini. The other authors have no conflicts of interest to declare. Rolfo C. is a speaker for Merck Sharp and Dohme, AstraZeneca, COR2ED, Daiichi Sankyo, Physicians Education Resource, and Roche (CH); has research collaborations (nonfinancial support) with Guardant Health; advisory board activity: Archer, Inivata, Bayer U.C. LLC, Boston pharmaceutical, CEA, MD Serono, General Dynamics, MedStar, Novartis, Sanofi Genzyme-Regeneron. Provides expert testimony to Intellisphere, scientific board for Imagene, and is a coordinating PI for MD Serono Global PI LUNG itrapid@024 trial. Research grant from LCRF-Pfizer unrelated to the current work. Gandara D.R. received honoraria from Merck, research funding from Merck, Amgen, Genentech, AstraZeneca, Astex Pharmaceuticals, and has consulting or advisory role for AstraZeneca, Guardant Health, OncoCyte, IO Biotech, Roche/Genentech, and Adagene. Kasi P.M. reports personal fees from Foundation Medicine, MSD Oncology/Merck, Tempus, Bayer, Lilly, Delcath Systems, QED Therapeutics, Servier, Taiho Oncology, Exact Sciences, Daiichi Sankyo/AstraZeneca, Eisai, Seattle Genetics, SAGA Diagnostics, Illumina, BostonGene, Guardant Health, and Taiho; personal fees and other support from Elicio Therapeutics; other support from Precision Biosensors Inc.; and grants from Merck, Novartis, and Agenus Bio. Malapelle U. received personal fees (consultant and/or speaker bureau) from Boehringer Ingelheim, Roche, MSD, Amgen, Thermo Fisher Scientifics, Eli Lilly, Diaceutics, GSK, AstraZeneca, Janssen, Diatech, Novartis, and Hedera. The other authors declare no competing interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Circulating tumor DNA (ctDNA) detection has multiple promising applications in oncology, but the road toward implementation in clinical practice is unclear. We aimed to support the implementation process by exploring potential future pathways of ctDNA testing. To do so, we studied four ctDNA-testing applications in two cancer types and elicited opinions from 30 ctDNA experts in the Netherlands. Our results showed that the current available evidence differed per application and cancer type. Tumor profiling and monitoring treatment response were found most likely to be implemented in non-small cell lung cancer (NSCLC) within 5 years. For colorectal cancer, applications of ctDNA testing were found to be at an early stage in the implementation process. Demonstrating clinical utility was found a key aspect for successful implementation, but there was no consensus regarding the evidence requirements. The next step toward implementation is to define how clinical utility of biomarkers should be evaluated. Finally, these data indicate that specific challenges for each clinical application and tumor type should be appropriately addressed in a deliberative process involving all stakeholders to ensure implementation of ctDNA testing and timely access for patients., (© 2023 The Authors. Molecular Oncology published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.)

Several studies have demonstrated the prognostic value of circulating tumor DNA (ctDNA); however, the correlation of mean tumor molecules (MTM)/ml of plasma and mean variant allele frequency (mVAF; %) with clinical parameters is yet to be understood. In this study, we analyzed ctDNA data in a pan-cancer cohort of 23 543 patients who had ctDNA testing performed using a personalized, tumor-informed assay (Signatera™, mPCR-NGS assay). For ctDNA-positive patients, the correlation between MTM/ml and mVAF was examined. Two subanalyses were performed: (a) to establish the association of ctDNA with tumor volume and (b) to assess the correlation between ctDNA dynamics and patient outcomes. On a global cohort, a positive correlation between MTM/ml and mVAF was observed. Among 18 426 patients with longitudinal ctDNA measurements, 13.3% had discordant trajectories between MTM/ml and mVAF at subsequent time points. In metastatic patients receiving immunotherapy (N = 51), changes in ctDNA levels expressed both in MTM/ml and mVAF showed a statistically significant association with progression-free survival; however, the correlation with MTM/ml was numerically stronger., (© 2023 Natera, Inc. Molecular Oncology published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.)

Circulating tumor DNA (ctDNA) is an emerging biomarker of liquid biopsy for cancer. But it remains a challenge to achieve simple, sensitive and specific detection of ctDNA because of low abundance and single-base mutation. In this work, an excitation/emission-enhanced heterostructure photonic crystal (PC) array synergizing with entropy-driven circuit (EDC) was developed for high-resolution and ultrasensitive analysis of ctDNA. The donor donor-acceptor FÖrster resonance energy transfer ("DD-A" FRET) was integrated in EDC based on the introduction of simple auxiliary strand, which exhibited higher sensitivity than that of traditional EDC. The heterostructure PC array was constructed with the bilayer periodic nanostructures of nanospheres. Because the heterostructure PC has the adjustable dual photonic band gaps (PBGs) by changing nanosphere sizes, and the "DD-A" FRET can offer the excitation and emission peak with enough distance, it helps the successful matches between the dual PBGs of heterostructure PC and the excitation/emission peaks of "DD-A" FRET; thus, the fluorescence from EDC can be enhanced effectively from both of excitation and emission processes on heterostructure PC array. Besides, high-resolution of single-base mutation was obtained through the strict recognition of EDC. Benefiting from the specific spectrum-matched and synergetic amplification of heterostructure PC and EDC with "DD-A" FRET, the proposed array obtained ultrasensitive detection of ctDNA with LOD of 12.9 fM, and achieved the analysis of mutation frequency as low as 0.01%. Therefore, the proposed strategy has the advantages of simple operation, mild conditions (enzyme-free and isothermal), high-sensitivity, high-resolution and high-throughput analysis, showing potential in bioassay and clinical application., 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.)

This viewpoint summarizes findings from analyses of large personal patient databases of myeloproliferative neoplasms (MPNs) to assess the impact of thrombosis on mortality, disease progression, and second cancers (SC). Despite advances, the current incidence of arterial and venous thrombosis remains a challenge. These events appear to signal a more aggressive disease course, as evidenced by their association with myelofibrosis progression and mortality using multistate models and time-dependent multivariable analysis. Inflammatory biomarkers, such as the neutrophil-to-lymphocyte ratio (NLR), are associated with the aggressiveness of polycythemia vera (PV) and essential thrombocythemia (ET), linking thrombosis to SC risk. This suggests a common inflammatory pathway likely influencing cardiovascular disease and cancer incidence. Notably, this is observed more frequently in younger patients, likely due to prolonged exposure to MPN and environmental inflammatory triggers. These data underscore the need for new studies to validate these associations, delineate the sequence of events, and identify therapeutic targets to mitigate thrombotic events and potentially improve overall patient outcomes in MPN., (© 2024. The Author(s).)

Background: Cancer patients are more susceptible to an aggressive course of COVID-19. Developing biomarkers identifying cancer patients at high risk of COVID-19-related death could help determine who needs early clinical intervention. The miRNAs hosted in the genomic regions associated with the risk of aggressive COVID-19 could represent potential biomarkers for clinical outcomes., Patients and Methods: Plasma samples were collected at The University of Texas MD Anderson Cancer Center from cancer patients (N = 128) affected by COVID-19. Serum samples were collected from vaccinated healthy individuals (n = 23) at the Municipal Clinical Emergency Teaching Hospital in Timisoara, Romania. An in silico positional cloning approach was used to identify the presence of miRNAs at COVID-19 risk-associated genomic regions: CORSAIRs (COvid-19 RiSk AssocIated genomic Regions). The miRNA levels were measured by RT-qPCR., Results: We found that miRNAs were enriched in CORSAIR. Low plasma levels of hsa-miR-150-5p and hsa-miR-93-5p were associated with higher COVID-19-related death. The levels of hsa-miR-92b-3p were associated with SARS-CoV-2 test positivity. Peripheral blood mononuclear cells (PBMC) increased secretion of hsa-miR-150-5p, hsa-miR-93-5p, and hsa-miR-92b-3p after in vitro TLR7/8- and T cell receptor (TCR)-mediated activation. Increased levels of these three miRNAs were measured in the serum samples of healthy individuals between one and nine months after the second dose of the Pfizer-BioNTech COVID-19 vaccine. SARS-CoV-2 infection of human airway epithelial cells influenced the miRNA levels inside their secreted extracellular vesicles., Conclusions: MiRNAs are enriched at CORSAIR. Plasma miRNA levels can represent a potential blood biomarker for predicting COVID-19-related death in cancer patients., (© 2024. The Author(s).)

Objectives: To evaluate the effect of procalcitonin-guided management on the duration of antibiotic therapy in critically ill cancer patients with sepsis., Design: Randomized, controlled, single-blinded trial., Setting: A comprehensive multidisciplinary cancer hospital in Jordan., Patients: Adults with cancer treated in the ICU who were started on antibiotics for suspected infection, met the SEPSIS-3 criteria, and were expected to stay in the ICU greater than or equal to 48 hours., Interventions: Patients were randomized to the procalcitonin-guided or standard care (SC) arms. All patients had procalcitonin measured daily, up to 5 days or until ICU discharge or death. For the procalcitonin arm, a procalcitonin-guided algorithm was provided to guide antibiotic management, but clinicians were allowed to override the algorithm, if clinically indicated. In the SC arm, ICU clinicians were blinded to the procalcitonin levels., Measurements and Main Results: Primary outcome was time to antibiotic cessation. We also evaluated the number of antibiotic-free days at 28 days, hospital discharge, or death, whichever came first, and antibiotic defined daily doses (DDDs). We enrolled 77 patients in the procalcitonin arm and 76 in the SC arm. Mean age was 58 ± 14 (sd) years, 67% were males, 74% had solid tumors, and 13% were neutropenic. Median (interquartile range [IQR]) Sequential Organ Failure Assessment scores were 7 (6-10) and 7 (5-9) and procalcitonin concentrations (ng/mL) at baseline were 3.4 (0.8-16) and 3.4 (0.5-26), in the procalcitonin and SC arms, respectively. There was no difference in the median (IQR) time to antibiotic cessation in the procalcitonin and SC arms, 8 (4-11) and 8 (5-13), respectively (p = 0.463). Median (IQR) number of antibiotic-free days were 20 (17-24) and 20 (16-23), (p = 0.484) and total DDDs were 1541.4 and 2050.4 in the procalcitonin and SC arms, respectively., Conclusions: In critically ill cancer patients with sepsis, procalcitonin-guided management did not reduce the duration of antibiotic treatment., Competing Interests: The authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2024 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine.)

The fragmentation patterns of cell-free DNA (cfDNA) in plasma can potentially be utilized as diagnostic biomarkers in liquid biopsy. However, our knowledge of this biological process and the information encoded in fragmentation patterns remains preliminary. Here, we investigated the cfDNA fragmentomic characteristics against nucleosome positioning patterns in hematopoietic cells. cfDNA molecules with ends located within nucleosomes were relatively shorter with altered end motif patterns, demonstrating the feasibility of enriching tumor-derived cfDNA in patients with cancer through the selection of molecules possessing such ends. We then developed three cfDNA fragmentomic metrics after end selection, which showed significant alterations in patients with cancer and enabled cancer diagnosis. By incorporating machine learning, we further built high-performance diagnostic models, which achieved an overall area under the curve of 0.95 and 85.1% sensitivity at 95% specificity. Hence, our investigations explored the end characteristics of cfDNA fragmentomics and their merits in building accurate and sensitive cancer diagnostic models., Competing Interests: Declaration of interests Y.A., J.J., and K.S. have filed patent applications based on the method developed in this work., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objective: This study examined the relationship between cystatin C (CysC) levels and all-cause, cardiovascular disease (CVD), and cancer mortality in US metabolic syndrome (MetS) patients., Methods: The 1999-2002 National Health and Nutrition Examination Survey (NHANES) prospective cohort research included 1980 MetS participants. To assess CysC levels and all-cause, CVD, and cancer mortality, fitted curves, Kaplan-Meier survival curves, Cox regression analysis, and receiver operating characteristic curves were performed., Results: During a mean follow-up of 15.3 ± 5.4 years, a total of 819 deaths occurred. The fitted and Kaplan-Meier survival curves revealed that greater CysC levels were linked to higher all-cause, CVD, and cancer mortality rates (P < .05). After adjusting for variables, CysC level was associated with all-cause, CVD, and cancer mortality at 1.63 (1.42-1.88), 1.53 (1.19-1.95), and 1.53 (1 ∼ 2.32), respectively (P < .05). Tertile models showed consistent results: high CysC Tertile participants showed higher risk of all-cause mortality (HR 1.87; 1.43-2.45), CVD mortality (HR 1.97, 1.15 ∼ 3.38), and cancer mortality (HR 1.72, 1.01 ∼ 2.91) compared to those in the lowest tertile (P < .05). Subgroup studies by sex and other characteristics confirmed the findings. CysC demonstrated the higher predictive efficacy across mortality outcomes, followed by eGFR, outperforming urea nitrogen, creatinine, uric acid, and C-reactive protein. CysC alone exhibited substantial predictive value for all-cause (AUC 0.773; P < .05) and CVD mortality (AUC 0.726; P < .05). Combining CysC with age enhanced predictive value for all-cause mortality to 0.861 and CVD mortality to 0.771 (P < .05)., Conclusion: MetS patients with elevated CysC levels have a higher risk of all-cause, CVD, and cancer death. CysC may predict MetS all-cause and CVD mortality., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society.)

Programmed cell death-ligand 1 positive (PD-L1 + ) exosomes play a crucial role in the realm of cancer diagnosis and treatment. Nevertheless, due to the intricate nature of biological specimens, coupled with the heterogeneity, low refractive index (RI), and scant surface coverage density of exosomes, traditional surface plasmon resonance (SPR) sensors still do not meet clinical detection requirements. This study utilizes the exceptional electrical and optical attributes of single-walled carbon nanotubes (SWCNTs) as the substrate for SPR sensing, thereby markedly enhancing sensitivity. Furthermore, sp 2 hybridized SWCNTs have the ability to load specific recognition elements. Additionally, through the coordination interaction of Ti with phosphate groups and the ferromagnetism of Fe 3 O 4 , efficient exosomes isolation and enrichment in complex samples are achievable with the aid of an external magnetic field. Owing to the high-quality and high-RI of Fe 3 O 4 @TiO 2 , the response signal experiences amplification, thus further improving the performance of the SPR biosensor. The linear range of the SPR biosensor constructed by this method is 1.0 × 10 3 to 1.0 × 10 7 particles/mL, with a limit of detection (LOD) of 31.9 particles/mL. In the analysis of clinical serum samples, cancer patients can be differentiated from healthy individuals with an Area Under Curve (AUC) of 0.9835. This study not only establishes a novel platform for exosomes direct detection but also offers new perspectives for the sensitive detection of other biomarkers., 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.)

To enhance the precision and reliability of early disease detection, especially in malignancies, an exhaustive investigation of multi-target biomarkers is essential. In this study, an advanced integrated electrochemical biosensor array that demonstrates exceptional performance was constructed. This biosensor was developed through a controllable porous-size mechanism and in-situ modification of carbon nanotubes (CNTs) to quantify multiplex biomarkers-specifically, C-reaction protein (CRP), carbohydrate antigen 125 (CA125), and carcinoembryonic antigen (CEA)-in human serum plasma. The fabrication process involved creating a highly ordered three-dimensional inverse-opal structure with the CNTs (pCNTs) modifier through microdroplet-based microfluidics, confined spatial self-assembly of nanoparticles, and chemical wet-etching. This innovative approach allowed for direct in-situ modification of nanomaterial onto the surface of electrode array, eliminating secondary transfer and providing exceptional control over structure and stability. The outstanding electrochemical performance was achieved through the synergistic effect of the pCNTs nanomaterial, aptamer, and horseradish peroxidase-labeled (HRP-) antibody. Additionally, the integrated biosensor array platform comprised multiple individually addressable electrode units (n = 11), enabling simultaneous multi-parallel/target testing, thereby ensuring accuracy and high throughput. Crucially, this integrated biosensor array accurately quantified multiplex biomarkers in human serum, yielding results comparable to commercial methods. This integrated technology holds promise for point-of-care testing (POCT) in early disease diagnosis and biological analysis., 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 neutropenic diet (ND) is often recommended to people with cancer to reduce infection risk despite recommendations of clinical guidelines advising against its use. While recent literature suggests the ND does not reduce infection risk, other outcomes related to health, nutrition, and lifestyle are unknown. The aim of this review is to systematically scope the literature on the ND in people with cancer for all outcomes related to clinical health, nutrition, and lifestyle. Scientific databases were systematically searched. Eligible studies were in English, people with any cancer type, consuming an ND, any age group, date, or setting. Eligible study types were randomised control trials, observational studies, systematic reviews, and meta-analyses. Twenty-one studies met the inclusion criteria. Outcomes of interest found were infection rates, fever, mortality, antibiotic use, gastrointestinal side effects, comorbidities, biochemistry, hospitalisation, nutritional status, quality of life (QoL), well-being, and financial costs. Most research has focused on infection and mortality rates with few assessing hospitalisation rates, nutritional status, financial costs, and QoL. Most included studies found no significant differences between ND and comparator diet for mortality, antibiotics use, comorbidities, and QoL; however, several studies reported the ND significantly increased the risk of infection. Gaps in the literature included effect of ND on QoL in an adult population, microbiome, lifestyle changes, and financial burden. Further research is needed regarding how the ND affects the microbiome and QoL of its consumers, but in the interim, it is important for hospitals providing an ND to their patients to liberalise the ND wherever possible., Competing Interests: None., (© The Author(s) 2024.)

Objective: Hematological indicators in the early stage of PD-1 inhibitor treatment may show superior predictive ability of the occurrence of immune related adverse event (irAE) compared to the pre-treatment indicators, as the immune response is modulated during the PD-1 inhibitor treatment. The objective of this study was to investigate the predictive capabilities of biomarkers in the early treatment stage for immune related thyroid dysfunction (irTD), and explore the potential predictive cytokines., Methods: Medical records and blood test results of cancer patients treated with PD-1 inhibitor at a certain medical institution were collected. Logistic regression analysis was utilized to identify the predictive factors of irTD, ROC curves were plotted and the area under the curves (AUC) was calculated. Serum samples were collected before and during early treatment phase, cytokine detection was performed to explore potential predictive cytokines., Results: A total of 264 patients were enrolled, 58 developed irTD (21.97%), including 31 patients with thyrotoxicosis and 27 with hypothyroidism. There were no significant differences in demographic characteristics, tumor types and PD-1 inhibitors between patients with and without irTD. Multivariate logistic analysis showed that anti-thyroglobulin antibody (TgAb) (OR=2.831, 95%CI: 1.077-7.443, P =0.035) and anti-thyroperoxidase antibody (TPOAb) (OR=9.565, 95%CI: 3.399-26.921, P =0.000) in the early treatment phase were independent predictive factors for irTD, the AUC of early-stage biomarkers was larger than that of pre-treatment (0.655 vs 0.571); low level of TSH at the early stage (OR=0.162, 95%CI: 0.077-0.341, P =0.000) was significantly correlated with thyrotoxicosis; female (OR=3.889, 95%CI: 1.457-10.380, P =0.007) and positive TPOAb (OR=8.678, 95%CI: 2.656-28.357, P =0.000) at the early stage were significantly correlated with hypothyroidism. The AUCs of early-stage biomarkers were larger than that of pre-treatment both in thyrotoxicosis (0.812 vs 0.637) and hypothyroidism patients (0.728 vs 0.710). The increase of IL-16 (adjusted P =0.004), IL-12p70 (adjusted P =0.014), IL-17 (adjusted P =0.014), CCL-15 (adjusted P =0.014) and IL-1a (adjusted P =0.021) in the early treatment phase were positively correlated with irTD., Conclusions: Biomarkers at the early stage of PD-1 inhibitor treatment could predict irTD, and demonstrated stronger predictive ability compared to pre-treatment biomarkers. IL-16, IL-12p70, IL-17, CCL-15 and IL-1a could serve as potential predictive biomarkers for irTD., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Liu, Chen, Li, Cai, Ma, Yang, Zhang, Bai, Wu, Tang and Wang.)

Inflammation plays a crucial role in cancer development. The neutrophil-to-lymphocyte ratio (NLR), a measure of inflammation, is obtained from a complete blood count. However, little is known about the association between NLR and cancer in the general adult population in the United States. This study aimed to evaluate whether NLR is associated with cancer in American adults. This retrospective cross-sectional study included 28,016 adult participants from the National Health and Nutrition Examination Survey (NHANES) dataset spanning 2005 to 2018. Data on demographics (age, sex, race, marital status, Poverty-Income Ratio, education level), lifestyle factors (smoking, alcohol consumption, body mass index), medical conditions (hypertension, diabetes, cardiovascular disease), and laboratory parameters (hemoglobin, platelet count, alanine aminotransferase, creatinine, albumin, and lactate dehydrogenase), were collected. Logistic regression analysis was used to investigate the research objectives. Of the total 28,016 participants, 2639 had cancer. The mean age was 49.6 ± 17.6 years, and 50% were male. A positive association between NLR and cancer risk was observed after multivariate adjustment (OR = 1.20, 95% confidence interval (CI) = 1.05-1.36, p = 0.006). Similar patterns were observed in subgroup analyses (all p-values for interaction > 0.05). A higher NLR was directly correlated with an increased risk of developing cancer in adults., (© 2024. The Author(s).)

Background: Although associations have been reported linking pretreatment thrombocytosis to cancer survival outcomes, the validity and strength of existing observational evidence have been contested. This study aimed to conduct an umbrella review to comprehensively appraise the strength, validity and credibility of these reported associations., Methods: We searched Medline, Embase and Cochrane Database of Systematic Reviews from inception to 8 April 2023 to retrieve meta-analyses of observational studies. Meta-analyses were re-performed using a random-effect model and the strength of evidence was graded as convincing, highly suggestive, suggestive and weak according to seven pre-defined quantitative criteria reflecting statistical significance, amount of data, heterogeneity, and evidence of bias. The quality of review was appraised using the AMSTAR2 checklist. The umbrella review was reported adhering to the PRISMA guideline and was registered on PROSPERO (CRD42023455391)., Results: A total of 21 unique meta-analyses investigating ten cancer subtypes were included. All meta-analyses reported inferior survival outcome in cancer patients with pretreatment thrombocytosis, and 18 of them (85.7%) yielded statistically significant results (P < 0.05). Consistent effects were observed across meta-analyses that adopted different cut-off values (i.e. platelet count > 300 or 400 × 10 9 /L) to define thrombocytosis. Although evidence appraisal did not identify convincing evidence (Class I), the associations of thrombocytosis with inferior overall survival of lung, gastric, colorectal cancer and malignant mesothelioma were classified as highly suggestive evidence (Class II). According to AMSTAR2 ratings, no meta-analysis was identified with high or moderate quality., Conclusions: Our findings consolidated the association between pretreatment thrombocytosis and poor survival outcomes in various cancers. Nonetheless, the absence of convincing associations indicates a need for further large-scale, high-quality evidence to confirm whether platelets can serve as a prognostic predictor or a therapeutic target., (© 2024. The Author(s).)

Background: In primary care, health professionals use blood tests to investigate nonspecific presentations to inform referral decisions. Reference ranges for the commonly used blood tests in western countries were developed in predominately White populations, and so may perform differently when applied to non-White populations. Knowledge of ethnic variation in blood test results in healthy/general populations could help address ethnic inequalities in cancer referral for diagnosis and outcomes., Objective: This systematic review explored evidence of ethnic differences in the distribution of selected blood test results among healthy/general populations to inform future research aimed at addressing inequalities in cancer diagnosis., Methods: We searched PubMed and EMBASE to identify studies reporting measures of haemoglobin, MCV, calcium, albumin, platelet count, and CRP in nondiseased adults from at least 2 different ethnic groups. Two reviewers independently screened studies, completed data extraction and quality assessment using an adapted Newcastle-Ottawa scale. Participants were stratified into White, Black, Asian, Mixed, and Other groups. Data were synthesised narratively and meta-analyses were conducted where possible., Results: A total of 47 papers were included. Black men and women have lower average values of haemoglobin, MCV, and albumin, and higher average values of CRP relative to their White counterparts. Additionally, Black men have lower average haemoglobin than Asian men, whereas Asian women have lower average CRP values when compared with White women., Conclusions: There is evidence of ethnic differences in average values of haemoglobin, MCV, CRP, and albumin in healthy/general populations. Further research is needed to explore the reasons for these differences. Systematic review registration: CRD42021274580., (© The Author(s) 2024. Published by Oxford University Press.)

Several epidemiologic studies have investigated the circulating levels of albumin, bilirubin, and uric acid (UA) in relation to cancer risk; however, they have provided equivocal evidence. In this prospective case-cohort study, we measured the plasma levels of albumin, bilirubin, and UA and investigated their association with cancer incidence in 3584 case patients and 4270 randomly selected participants with a median follow-up of 15.8 years. The adjusted hazard ratios (HRs) and 95% CIs of total cancer for the highest quartile (Q4) versus lowest quartile (Q1) was 0.77 (95% CI, 0.67-0.90; P <.001 for trend) for albumin. This association was attenuated after excluding liver cancer cases with lower plasma albumin levels. Plasma bilirubin levels were positively related to liver cancer but inversely to total cancer after excluding liver cancer with, for Q4 versus Q1, an adjusted HR of 0.86 (95% CI, 0.74-0.99; P = .015 for trend). Plasma UA levels were not dose-responsively associated with total cancer risk. Higher plasma bilirubin levels were associated with a decreased risk of total cancer after excluding liver cancer, which is likely attributed to the antioxidant properties of bilirubin., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Circulating tumor cell (CTC) numbers in the blood of cancer patients can indicate the progression and invasiveness of tumors, and their prognostic and predictive value has been repeatedly demonstrated. However, the standard baseline CTC count at the beginning of treatment, while informative, is not completely reliable and may not adequately reflect the state of the disease. A growing number of studies indicate that the long-term monitoring of CTC numbers in the same patient provides more comprehensive prognostic data and should be incorporated into clinical practice, as a factor that contributes to therapeutic decisions. This review describes the current status of CTC enumeration as a prognostic and predictive factor, highlights the shortcomings of current solutions, and advocates for longitudinal CTC analysis as a more effective method of the evaluation of developing disease, treatment efficacy, and the long term-monitoring of the minimal residual disease. As evidenced by the described reports, the longitudinal monitoring of CTCs should provide a better and more sensitive prediction of the course of the disease, and its incorporation in clinical practice should be beneficial.

Background: The goal is to study the changes of natural killer T-like (NKT-like) cells with age and explore the value of NKT-like cell changes in the evaluation of immune function and prognosis of tumor patients., Methods: From January 2021 to December 2021, 19 patients with lung cancer, 37 patients with lymphoma, 16 patients with multiple myeloma (MM), 13 patients with acute lymphoblastic leukemia (ALL), 70 patients with acute myeloid leukemia (AML) treated in the Affiliated Hospital of Chengde Medical College and 141 healthy volunteers included in the healthy control group were recruited to study the change trend of NKT-like cells with age and changes in different tumor patients., Results: With the increase of age, NKT-like cells in peripheral blood increased gradually in healthy people, mainly composed of CD8+NKT-like cells and CD8-CD4-NKT-like cells. The proportion of NKT-like cells in the lymphoma group and AML group was significantly higher than that in the control group (p < 0.05). The proportion of CD8+NKT-like cells decreased in the Lymphoma, AML, ALL, and lung cancer groups (p < 0.05), there was no statistical significance between MM group and control group (p > 0.05)., Conclusions: With the increase of age, NKT-like cells in peripheral blood gradually increased in healthy people and were mainly composed of CD8+NKT-like cells and CD8-CD4-NKT-like cells. The increase of CD8+NKT-like cells in peripheral blood has important reference value for the evaluation of immune function and prognosis of patients with lymphoma, AML, ALL, and lung cancer and provides direction for immunotherapy.

Background: Ferritin is an iron deposition protein and a commonly ordered clinical test. While high levels may signify iron deposition, the majority are due to metabolic, inflammatory, infectious, and malignant disorders. The association between ferritin elevations < 1000 μg/L and long-term mortality is well demonstrated. The association between extreme ferritin elevations, namely ferritin levels over 10,000 μg/L, and short-term mortality, as well as predictors of mortality, has not been defined., Methodology: A retrospective chart study was designed in an academic hospital to analyze the clinical, laboratory, and mortality characteristics of patients whose ferritin is over 10,000 μg/L. Patients from 2012 to 2023 in a large academic center's electronic medical records were analyzed. Demographics, underlying disorders, laboratory values, mortality status, and days to mortality were acquired. Multivariate logistic regression analysis was used to define predictors of mortality. The Kaplan-Meier survival curve was used to analyze survival., Results: Sixty-seven patients were identified to have ferritin levels over 10,000 μg/L. The most common underlying disorders were infectious diseases and malignancies. Predictors of mortality in the multivariate logistic regression model were also infectious disease (odds ratio (OR) = 5.35), and malignancy (OR = 6.56), as well as age (OR = 1.05). The area under the curve of the model was .86. 1-year mortality was 62%. Of the patients who died, median survival was 5 days; 30- and 90-day mortality were 80% and 92%, respectively., Discussion: Extreme hyperferritinemia is associated with high short-term mortality. Ferritin can be used as a marker of poor prognosis, particularly among patients with infection and malignancy., (© 2024. The Author(s), under exclusive licence to Royal Academy of Medicine in Ireland.)

Body weight, body mass index (BMI), Nutrition Risk Screening 2002 (NRS2002), and prognostic nutritional index (PNI) are among vital nutrition status indices employed during cancer treatment. These have also been associated with levels of blood chemistry panels (BCPs), which are touted as significant indicators of disease prognosis. However, it remains unclear which nutrition status index better predicts future trends in specific BCPs. Using the records of 407 cancer patients, we retrospectively examined the potential of nutritional status indices at baseline for predicting changes in specific BCPs over a 6-week period. Generally, both serum biochemical parameters and nutrition status indices fluctuated over the study period among study participants. PNI was often linearly associated with blood cell counts (white blood cells [WBCs] and hemoglobin) compared with anthropometric-based nutrition status indices. Increase in body weight was protective against having abnormal lymphocyte levels at 6 weeks (odds ratio [OR]: 0.960-0.974; CI: 0.935-0.997; P < 0.05), while increase in baseline PNI was associated with 0.865-0.941 and 0.675-0.915 odds of having future abnormal WBC and lymphocyte levels, respectively. Increases in PNI were also protective against having future abnormal albumin levels (OR: 0.734-0.886) and 8.5-12.5% decreases in the odds of having an abnormal C-reactive protein level in subsequent visits. Changes in NRS2002 tended to be associated with the odds of having future abnormal blood glucose levels. In conclusion, the serum biochemistry-derived nutrition status index, PNI, is a more consistent measure as an early indicator to track the trends of future changes in the BCPs of cancer patients. This implies that PNI could be targeted as an early-warning measure with relevant preventive interventions for patients at risk of malnutrition., 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 Inc. All rights reserved.)