Feasible Biomarker Research Articles

The Metabolic Profile of Plasma During Epileptogenesis in a Rat Model of Lithium-Pilocarpine-Induced Temporal Lobe Epilepsy.

Temporal lobe epilepsy (TLE) arises mostly because of an initial injury. Certain stimuli can make a normal brain prone to repeated, spontaneous seizures via a process called epileptogenesis. This study examined the plasma metabolomics profile in rats with the induced TLE to identify feasible biomarkers that can distinguish progression of epileptogenesis in three different time points and reveal the underlying mechanisms of epileptogenesis. Status epilepticus (SE) was induced by repetitive intraperitoneal injections of low-dose lithium chloride-pilocarpine hydrocholoride. Blood samples were collected 48h, 1week, and 6weeks after SE, respectively. Plasma metabolites were analyzed by nuclear magnetic resonance (NMR) spectrometry. Statistical analysis was performed using MetaboAnalyst 6.0. An orthogonal partial least squares discriminant analysis (OPLS-DA) model was employed to represent variations between the TLE model groups and respective controls. Volcano plot analysis was used to identify key features, applying a fold-change criterion of 1.5 and a t-test threshold of 0.05. 48h after SE, dimethyl sulfone (DMSO2) and creatinine levels were decreased, whereas glycine and creatine levels were increased. The only metabolite that changed 1week after SE was pyruvic acid, which was increased compared to its control level. Lactic acid, pyruvic acid, and succinic acid levels were increased 6weeks after SE. The identified metabolites were especially related to the tricarboxylic acid cycle and glycine, serine, and threonine metabolism. The results illustrate that distinct plasma metabolites can function as phase-specific biomarkers in TLE and reveal new insights into the mechanisms underlying SE.

Personalized Medicine in Chronic Rhinosinusitis: Treatable Traits Using Biologics for Unmet Needs.

Chronic rhinosinusitis (CRS) is a prevalent airway disease, leading to health, social, and economic burdens, and substantially impairs quality of life. As CRS is heterogeneous and contains diverse pathogenesis, treatment outcomes and prognosis vary from curative to intractable. Inflammatory endotypes of CRS are divided into 3 types-type 1, type 2 and type 3-based on cytokines promoted. Tissue/blood eosinophilia seems to be the most reliable and feasible biomarker for type 2 CRS in clinical settings, although the cutoff level of eosinophilia remains to be elucidated. In East Asia, the predominant pathogenesis has changed from neutrophilic type 3 inflammation to eosinophilic type 2 inflammation over the past decades. The treatment strategy for CRS has also evolved from classical phenotype-based "reliever-controller" treatment to endotype-based "treatable traits" treatment. "Treatable traits" treatment is a personalized approach for the management of airway disease with complex and heterogeneous conditions. In CRS, traits can be grouped into sinonasal, extra-nasal and risk factor/behavioral domains. Type 2 CRS is one of the sinonasal traits, and biologics targeting immunoglobulin E, interleukin (IL)-5 and its receptor, IL-4/IL-13 receptor (IL-4/IL-13R) and thymic stromal lymphopoietin are the corresponding treatments for this trait. Proper use of these biologics can achieve high efficacy with patient satisfaction, leading to clinical remission. However, some cases show marked hypereosinophilia after the reduction or discontinuation of systemic corticosteroid or the switching of biologics from anti-IL-5/IL-5R to anti-IL-4Rα monoclonal antibody. More precise research on CRS targeting endotype, genotype, regiotype and theratype is needed to address the unmet needs and refine the "treatable traits" treatment of CRS.

Circulating Tumor cells and multiple indicators combined to identify the risk of poorer prognosis in patients with resected non-small cell lung cancer

BackgroundSurgical resection is an important treatment option for patients with non-small cell lung cancer (NSCLC). However, recurrence and survival rates remain a cause of concern. To further improve prognosis, more studies have focused on liquid biopsy, which has significant value as a prognostic factor for defining the risk stratification of postoperative NSCLC patients. This study aimed to identify circulating tumor cells (CTCs) as biomarkers that indicate a poor prognosis, combined with multiple indicators to determine prognostic risks in advance and develop individualized treatment strategies.MethodsBetween November 2015 and August 2018, 65 radical resected patients with NSCLC were analyzed. Preoperative CTCs were collected, and follow-up lasted until August 2023. Overall survival (OS) and disease-free survival (DFS) were the primary outcomes.ResultsWith an 11 CTC unit threshold, the high preoperative CTC level group had worse OS and DFS than the low-level group, suggesting that preoperative CTC levels have prognostic value. Time-dependent receiver operating characteristic (ROC) curves also showed satisfactory predictive efficiency of CTCs. Univariate analysis revealed that preoperative CTC levels were significantly associated with increasing risks for OS and DFS. Moreover, we combined CTCs and multiple indicators to provide a reference for a group at high risk of adverse outcomes.ConclusionsCTCs serve as feasible biomarkers for predicting postoperative prognosis in NSCLC patients. The combination of hematological, radiological, and pathological features could be valuable tools to guide postoperative management and treatment decisions in these patients. A multimodal prognostic approach is important for the clinical evaluation of lung cancer.

Characterization of pulsations in the brain and cerebrospinal fluid using ultra‐high field magnetic resonance imaging

AbstractBackgroundBrain fluid flow plays a crucial role in maintaining brain health by eliminating potentially harmful waste products like amyloid‐beta and tau [1‐2]. This process is potentially facilitated by pulsations in the perivascular space, influenced by the neurovascular unit and autonomic nervous system, which may vary in brain diseases such as Alzheimer’s disease (AD) [3‐4]. Using a 7 Tesla MRI scanner and ultrafast echo‐planar imaging (EPI), we developed a non‐invasive neuroimaging methodology to characterize the in‐vivo frequency and amplitude responses of pulsations of cerebrospinal fluid (CSF) flow.MethodBrain images from six volunteers were acquired using a 7T MRI Scanner and an in‐house developed 16‐channel Tic‐Tac‐Toe transmit array with a 32‐channel receive coil. The human‐connectome EPI multiband MR sequence was optimized to present a real‐time visualization of the CSF flow in the brain. For the first volunteer, two axial and one sagittal slices were obtained, while whole‐brain coverage was acquired for the remaining volunteers, where the acquisition was divided into 19 slabs, each consisting of 3 axial slices. A spectral analysis based on Fast Fourier Transform (FFT) was conducted for the whole brain and grey matter, white matter, and CSF regions.ResultFigure 1 presents the processed axial and sagittal slices acquired from the first volunteer, demonstrating the presence of a periodic variation of the CSF signal. Figure 2 presents the identification of peaks in the spectrum acquisitions of whole‐brain segments for one volunteer, which exhibited similar frequencies, magnitudes and bandwidths among different volunteers. Quantitative results of this analysis are summarized in Table 1.ConclusionThis project developed a real‐time visualization of CSF pulsations based on a non‐invasive ultrafast EPI obtained with a 7T MRI scanner. The identification of similar frequency peaks (around 0.3, 0.8, 1.1, 2.3 and 3.1 Hz) and magnitudes among healthy volunteers suggests its potential as a feasible biomarker. Future work will examine this technique’s potential to identify changes in brain fluid dynamics associated with AD progression and pathology.Funding: NIH R01AG063525, R01MH111265, University of Pittsburgh CRC's RRID:SCR_022735.

Predictive value of neutrophil-lymphocyte ratio in assessing the outcomes of diabetic foot ulcer.

To assess the correlation of neutrophil-lymphocyte ratio with clinical outcomes in diabetic foot ulcer cases. The retrospective, cross-sectional, single-centre study was conducted at Section of Vascular Surgery, Aga Khan University Hospital, Karachi (Pakistan), and comprised data from January 2019 to January 2022 of diabetic foot inpatients of either gender aged at least 18 years. Hospital complications and outcomes were noted along with other data on a self-designed proforma. Diagnostic performance of neutrophil-lymphocyte ratio and its correlation with qualitative variables were assessed. Data was analysed using SPSS 26. Of the 130 patients with mean age 60.13+/-11.75 years, 98(75.4%) were males. Surgical intervention was needed in 118(90.8%) cases, with below-knee amputation being the most frequent procedure 38(32.3%). Neutrophil-lymphocyte ratio >4 was significantly associated with a higher grade of diabetic foot ulcer, major amputation, and postoperative complications (p<0.0001) as well as with in-hospital (p=0.008) and 1-year mortality (p=0.01). Neutrophil-lymphocyte ratio could be potentially used as a sensitive and economically feasible biomarker for evaluating the prognosis of patients presenting with diabetic foot ulcers.

Circ_0089761 accelerates colorectal cancer metastasis and immune escape via miR-27b-3p/PD-L1 axis.

Circular RNAs have been implicated as critical regulators in the initiation and progression of colorectal cancer (CRC). This study was intended to elucidate the functional significance of the circ_0089761/miR-27b-3p/programmed cell death ligand 1 (PD-L1) axis in CRC. Our findings indicated that circ_0089761 expression was significantly elevated in CRC tissues and cell lines. Furthermore, the high expression of circ_0089761 was correlated with TNM stage and tumor size. Silencing circ_0089761 inhibited CRC cell proliferation, migration, and invasion, and increased apoptosis. Mechanistically, circ_0089761 facilitated its biological function by binding to miR-27b-3p to upregulate PD-L1 expression in CRC. Coculture experiments confirmed that low expression of circ_0089761 impeded CD8 + T cell apoptosis and depletion, activated CD8 + T cell function, and increased secretion of the immune effector cytokines IFN-γ, TNF-α, perforin, and granzyme-B. MiR-27b-3p inhibition or PD-L1 overexpression partially impeded CD8 + T cell function. The circ_0089761/miR-27b-3p/PD-L1 axis is postulated to exert pivotal functions in the mechanistic progression of CRC. Furthermore, it holds promising prospects as a feasible biomarker and therapeutic target for CRC.

Evaluation of feasibility and utility of urinary lipoarabinomannan assay against conventional sputum microscopy in the detection of tuberculosis among people with and without HIV infection

BackgroundTuberculosis (TB) is a major global public health challenge. Lipoarabinomannan (LAM) assessment in urine is a potential molecular diagnostic tool for TB. MethodsWe evaluated the feasibility and utility of urinary LAM in detecting TB along with sputum smear microscopy (SSM) and the TrueNAT test. In an observational cross-sectional pilot study, we collected sputum and urine samples from 240 subjects visiting the Designated Microscopy Center, Warangal during Apr-Sep 2021. LED microscopy, TrueNAT and liquid culture were performed on sputum while LAM test was conducted on urine samples. ResultsMean age of the subjects was 45.1 (SD = 16.1) years. The majority were men (66 %), married (89 %) and urban (52 %) subjects. Overall sensitivity of urine LAM was 63.6 % and specificity 80.1 % while that of LED microscopy were 59.6 % and 56.7 % respectively. TrueNAT had sensitivity of 58.6 % and specificity of 80.1 %. However, a combination of LAM + TrueNAT had 79.8 % sensitivity. Among PLHIV, LAM + SSM has better sensitivity than any other combination of these tests or alone across all CD4 count categories. ConclusionUrinary LAM can be a more useful, feasible and better TB diagnostic biomarker over LED microscopy in diagnosing TB among the subjects who have symptoms irrespective of HIV status and recommend further evaluation of next-generation urinary LAM diagnostics to reach the unreached through a point of care tool.

Procollagen C-protease enhancer protein promotes glioma growth by activating ERK signaling.

Procollagen C-proteinase enhancer (PCOLCE) promotes tumor progression in multiple cancers. However, the specific role of PCOLCE in gliomas remains enigmatic. In this study, we focused on analyzing PCOLCE expression and its correlation with clinicopathological parameters in glioma specimens; moreover, we explored the effects of PCOLCE in glioma proliferation in vitro and in vivo. A tissue microarray containing 159 human glioma specimens was pressed to explore the correlation between PCOLCE expression and the survival of glioma patients. Cell Counting Kit-8 (CCK8), colony formation, and immunoblot assays were used to detect the role of PCOLCE on cell proliferation in glioma. Furthermore, the in vivo role of PCOLCE was investigated using a subcutaneous glioma xenograft model. The expression of PCOLCE was higher in grade III and IV gliomas than in grade I and II gliomas. High PCOLCE expression was related to a remarkably worse prognosis in glioma patients. Additionally, PCOLCE downregulation impeded glioma cell proliferation. Furthermore, PCOLCE knockdown markedly abrogated p-ERK expression in glioma cells, whereas, it negligibly influenced p38 and JNK signaling. These results indicate that PCOLCE is a feasible prognostic biomarker for glioma, and PCOLCE-induced activation of ERK signaling may be a pro-growth mechanism in glioma cells.

Prognostic significance of tertiary lymphoid structures in gastric neuroendocrine carcinoma with association to delta-like ligand 3 and neuroendocrine expressions.

Gastric neuroendocrine carcinomas (NECs) are rare cancers with highly aggressive behavior. Although tertiary lymphoid structures (TLSs) are well-known prognostic factors in various cancers, their role in gastric NECs remain unexplored. Unique immunohistochemical subtypes of pulmonary NECs have been discovered, however, their feasibility in gastric NECs is unknown. The presence and maturation of TLSs (lymphoid aggregates, primary and secondary follicles) were assessed in 48 surgically resected gastric NECs and were compared with immunohistochemical subtypes, using a panel of ASCL1, NeuroD1, POU2F3, YAP1, and DLL3 with three neuroendocrine (NE) markers. Patients with secondary follicles had significantly better overall survival (OS) and recurrence-free survival (RFS; both, p = 0.004) than those without them. Based on the hierarchical clustering, gastric NECs were classified into all low/negative (31%), high-YAP1 (19%), high-DLL3/low-NE (29%), and high-NE (21%) expression groups. The high-DLL3/low-NE group was associated with absent TLSs (p = 0.026) and showed the worst OS (p = 0.026). Distant metastasis and a lack of secondary follicles were poor independent prognostic factors of OS and RFS. The assessment of TLSs is a feasible and potent biomarker for gastric NECs, thus enabling better prognosis and moreeffective immunotherapy. Furthermore, gastric NECs can be categorized as four immunohistochemically distinct groups, of which the high-DLL3/low-NE group has the worst OS with lack of TLSs.

Identification and evaluation of a serum microRNA panel to diagnose colorectal cancer patients.

Screening plays a crucial role in the early detection of colorectal cancer, greatly reducing mortality rates. The objective of this study was to identify a non-invasive diagnostic method utilizing serum microRNA expression for the diagnosis of colorectal cancer patients. The study consisted of three stages. In the first stage, 129 patients with colorectal cancer and 129 normal subjects were recruited as the training set for the development of a blood miRNA panel. The second stage involved recruiting 200 patients from each group as the validation cohort. Finally, a blinded study was conducted in the third stage, with 260 patients recruited to determine the predictive value of our miRNA panel. Serum samples were prospectively collected from colorectal cancer patients and normal subjects between 2017 and 2021 at Queen Mary Hospital in Hong Kong. Quantitative PCR was utilized to detect the serum levels of candidate microRNAs, and a multiple linear regression model was employed to formulate a serum microRNA panel for diagnosing colorectal cancer patients. The performance of the panel was evaluated using ROC analysis. Our study showed that the values of three pairs of serum microRNAs, namely miR-106b-5p/miR-1246, miR-106b-5p/miR-16 and miR-106b-5p/miR-21-5p, exhibited statistically significant differences between colorectal cancer patients and normal subjects. A serum microRNA panel formulated from these three pairs of microRNAs demonstrated high accuracy in diagnosing colorectal cancer patients from normal subjects, with an AUC of approximately 0.9. The serum miRNA test proved to be a feasible and promising non-invasive biomarker for the diagnosis of colorectal cancer patients in comparison to normal subjects.

Lymphocyte-to-Monocyte Ratio Predicts Survival for Intraductal Papillary Mucinous Neoplasm with Associated Invasive Carcinoma of the Pancreas: Results from a High-Volume Center.

Intraductal papillary mucinous neoplasm (IPMN) is an important precursor lesion of pancreatic cancer. Systemic inflammatory parameters are widely used in the prognosis prediction of cancer; however, their prognostic implications in IPMN with associated invasive carcinoma (IPMN-INV) are unclear. This study aims to explore the prognostic value of systemic inflammatory parameters in patients with IPMN-INV. From 2015 to 2021, patients with pathologically confirmed IPMN who underwent surgical resection at Peking Union Medical College Hospital were enrolled. The clinical, radiological, and pathological data of the enrolled patients were collected and analyzed. Preoperative systemic inflammatory parameters were calculated as previously reported. Eighty-six patients with IPMN-INV met the inclusion criteria. The lymphocyte-to-monocyte ratio (LMR) was the only systemic inflammatory parameter independently associated with the cancer-specific survival (CSS). An LMR higher than 3.5 was significantly associated with a favorable CSS in univariate (hazard ratio [HR] 0.305, p = 0.003) and multivariate analyses (HR 0.221, p = 0.001). Other independently prognostic factors included the presence of clinical symptoms, cyst size, N stage, and tumor differentiation. Additionally, a model including LMR was established for the prognosis prediction of IPMN-INV and had a C-index of 0.809. Preoperative LMR could serve as a feasible prognostic biomarker for IPMN-INV. A decreased LMR (cutoff value of 3.5) was an independent predictor of poor survival for IPMN-INV.

The evaluation of the expression pattern of the LncRNAs (AP006621.9, RP3-323A16.1, and HOXC-AS3), and their target genes (MTOR, TNF-α and TRAF6) in PBMC of long-term non-progressors and HIV-1 infected naive individuals

A selected group of individuals with HIV, known as Elite Controllers (ECs), are able to regulate the replication of the virus in their bodies without needing antiviral drugs. LncRNAs, a type of RNA, are essential components of the chain responsible for controlling transcription in the case of HIV. Researchers suggest that components such as mTOR, TNF-α, and TRAF6 are also actively involved in keeping the HIV infection under control. In this study, a bioinformatic approach was used to determine which long non-coding RNAs (lncRNAs) could bind to mTOR, TNF-α, and TRAF6. The expression levels of these three lncRNAs and their designated targets were then observed in 14 ECs, 45 HIV-positive patients, and 45 healthy control subjects. The results indicated that the expression of TNF-α and TRAF6 were notably greater in the ECs group than in the HIV-positive group (P < 0.0001). Moreover, lnc-HOXC-AS3 was strongly overexpressed in the ECs group when compared to the HIV-positive group (P < 0.0001). By contrast, no important variations were seen in the levels of RP3-323A16.1, and AP006621.9 between the two study groups. Investigations of the receiver-operating characteristic (ROC) curve determined that lnc-HOXC-AS3, TNF-α and TRAF6 had an AUC of 0.92, 0.91, and 0.86 respectively, suggesting that they could be used as feasible biomarkers for separating ECs from HIV-1 positive samples. A significant negative correlation was found between HOXC-AS3 with mTOR and between AP006621.9 with TNF-α and TRAF6 in the HIV-positive group. The expression patterns of the chosen factors, paired with the evidence gained from the ROC curve, suggests that these factors could play an important part in controlling HIV infection, and may be used to detect ECs from HIV positive samples.

Combined approach for predicting the efficacy of nivolumab in head and neck carcinoma by tissue and soluble expressions of PD-L1 and PD-L2.

Predictive biomarkers for nivolumab in recurrent or metastatic head and neck squamous cell carcinoma (RMHNSCC) have not yet been established. The tumor proportion score (TPS), combined positive score (CPS), and soluble forms of programmed cell death ligand-1 (PD-L1) and programmed cell death ligand-2 (PD-L2) were retrospectively analyzed in patients with RMHNSCC treated with nivolumab. The positivity rates for TPS (PD-L1), CPS (PD-L1), TPS (PD-L2), and CPS (PD-L2) were 73.8%, 78.2%, 56.4%, and 78.2%, respectively. Patients with high TPS (PD-L1), CPS (PD-L1), or CPS (PD-L1 and PD-L2) showed significantly prolonged progression-free survival. Favorable overall survival was associated with high CPS (PD-L1 and PD-L2) and low soluble PD-L1 and PD-L2 levels. The expressions of tissue and soluble PD-L1/2 were not correlated. Our study revealed that compared to PD-L1 expression alone, dual expression of PD-L1 and PD-L2 in tissue or soluble form could be feasible biomarkers in patients with RMHNSCC who received nivolumab.

Systemic immune-inflammation index in dural arteriovenous fistula: a feasible biomarker reflecting its clinical characteristics.

The systemic immune-inflammation index (SII), a marker of systemic inflammation, can be calculated using peripheral blood tests. Although the SII has been reported as a feasible biomarker in various cerebrovascular diseases, no studies have explored in dural arteriovenous fistula (DAVF). A retrospective cohort study was performed to test whether the SII reflects the clinical characteristics of DAVF and whether this index could serve as a feasible biomarker. This study included 28 patients who underwent endovascular treatment (39 sessions) for DAVF between 2014 and 2023. The SII was calculated using the following formula: platelet count multiplied by neutrophil count divided by lymphocyte count. We investigated the correlation between the SII and various clinical characteristics of DAVF, including symptom manifestation, and digital subtraction angiography findings. Additionally, we compared pre- and post-endovascular treatment changes in the SII. A significantly higher SII was observed in patients with multiple lesions, clinical symptoms (particularly aggressive symptoms), pseudophelebitic pattern (PPP), and sinus occlusion. Multivariate regression analysis revealed that the presence of symptoms (coefficient 270.9, P = 0.021) and PPP (coefficient 272.4, P = 0.017) were independent factors contributing to SII elevation. Notably, following endovascular treatment, there was a significant decrease in the elevated SII in patients whose symptoms resolved (P = 0.039) and where the DAVF was angiographically cured (P = 0.012). Elevation of the SII in patients with advanced DAVF and its decrease following endovascular treatment suggests that the SII reflects the disease condition and indicates its potential as a promising biomarker.

Utilizing RNA sequencing to identify gene expression markers of stroke-causing thrombi origin: A pilot study

IntroductionStroke embolic source have an unknown origin in 30-40% of cases. Mechanical thrombectomy for acute large vessel occlusion stroke has provided us with a method to directly retrieve the thrombi from patients for analysis. By collecting stroke-causing thrombi from known sources, we can then use high-throughput RNA sequencing (RNAseq) technology to directly measure the gene expression signatures of these clots. This may allow us to identify genetic markers to predict the cause of cryptogenic embolism. MethodsThis is a prospective study in which RNAseq was used to analyze cerebral thrombi retrieved by mechanical thrombectomy devices in acute ischemic stroke patients. Samples were separated into two groups based on known stroke thrombus etiology, including Carotid group (patients with ipsilateral >70% carotid stenosis) and Atrial fibrillation (AF) group (patients with atrial fibrillation). Gene expression was compared by RNAseq analysis between the groups. ResultsFrom October 2016 to September 2017, 8 thrombi (4 in Carotid group, 4 in Afib group) were included in this study. There were 131 genes that were significantly up- or down-regulated between the two groups defined as a false discovery rate ≤ 0.05 and a fold change ≥ 2. Twenty-six genes were selected as candidate gene biomarkers based on the criteria in the methods section. Candidate genes HSPA1B, which encodes a heatshock protein, and GPRC5B, which encodes a G-protein, showed the greatest fold differences in expression between the two groups. ConclusionThis study has shown that RNA sequencing of acute ischemic stroke thrombi is feasible and indentified potential novel biomarkers for identifying stroke-causing thrombi origin, especially in cryptogenic stroke.

Biomechanical imaging biomarker during chemoradiotherapy predicts treatment response in head and neck squamous cell carcinoma

Objective. For response-adapted adaptive radiotherapy (R-ART), promising biomarkers are needed to predict post-radiotherapy (post-RT) responses using routine clinical information obtained during RT. In this study, a patient-specific biomechanical model (BM) of the head and neck squamous cell carcinoma (HNSCC) was proposed using the pre-RT maximum standardized uptake value (SUVmax) of 18F-fluorodeoxyglucose (FDG) and tumor structural changes during RT as evaluated using computed tomography (CT). In addition, we evaluated the predictive performance of BM-driven imaging biomarkers for the treatment response of patients with HNSCC who underwent concurrent chemoradiotherapy (CCRT). Approach. Patients with histologically confirmed HNSCC treated with definitive CCRT were enrolled in this study. All patients underwent CT two times as follows: before the start of RT (pre-RT) and 3 weeks after the start of RT (mid-RT). Among these patients, 67 patients who underwent positron emission tomography/CT during the pre-RT period were included in the final analysis. The locoregional control (LC), progression-free survival (PFS), and overall survival (OS) prediction performances of whole tumor stress change (TS) between pre- and mid-RT computed using BM were assessed using univariate, multivariate, and Kaplan–Meier survival curve analyses, respectively. Furthermore, performance was compared with the pre and post-RT SUVmax, tumor volume reduction rate (TVRR) during RT, and other clinical prognostic factors. Main results. For both univariate, multivariate, and survival curve analyses, the significant prognostic factors were as follows (p < 0.05): TS and TVRR for LC; TS and pre-RT FDG-SUVmax for PFS; and TS only for OS. In addition, for 2 year LC, PFS, and OS prediction, TS showed a comparable predictive performance to post-RT FDG-SUVmax. Significance. BM-driven TS is an effective prognostic factor for tumor treatment response after CCRT. The proposed method can be a feasible functional imaging biomarker that can be acquired during RT using only routine clinical data and may provide useful information for decision-making during R-ART.

Pretherapeutic factors predicting conversion surgery in unresectable pancreatic ductal adenocarcinoma: A retrospective study.

Recently, conversion surgery (CS) has been reported to improve the prognosis in patients with unresectable pancreatic ductal adenocarcinoma (UR-PDAC) with a favorable response to intense chemotherapy or chemoradiotherapy. However, few pretherapeutic parameters predict the attainability of CS in patients with UR-PDAC. The present study aimed to explore the pretherapeutic predictors for the attainability of CS in patients with UR-PDAC. The present study retrospectively evaluated 130 patients with UR-PDAC treated at Gifu University Hospital (Gifu, Japan) from January 2015 to December 2021. Survival analysis was performed using the Simon and Makuch-modified Kaplan-Meier method. The hazard ratio (HR) was estimated using a time-varying Cox regression model. The association between each predictor and CS was evaluated using the univariate analysis and age-adjusted Fine-Gray sub-distribution hazard model. The bootstrap bias-corrected area under the receiver operating characteristic curve analysis for predicting CS was used to assess the cut-off values for each predictor. The cumulative incidence rate was calculated with CS as the outcome when divided into two groups based on the cut-off value of each pretherapeutic predictor. Among the 130 patients included in the analysis, only 14 (11%) underwent CS. The median survival time was significantly longer in patients who underwent CS compared with patients without CS (56.3 vs. 14.1 months; P<0.001). The age-adjusted Fine-Gray sub-distribution hazard regression showed that the total protein (TP) [HR 2.81, 95% confidence interval (CI) 1.19-6.65; P=0.018], neutrophil-to-lymphocyte ratio (NLR) (HR 0.53, 95% CI 0.31-0.90; P=0.020), and lymphocyte-to-monocyte ratio (LMR) (HR 1.28, 95% CI 1.07-1.53; P=0.006) were significantly associated with CS. Moreover, TP ≥6.8, NLR <2.84 and LMR ≥3.87 were associated with a higher cumulative incidence of CS. In conclusion, pretherapeutic TP, NLR and LMR are clinically feasible biomarkers for predicting the attainability of CS in patients with UR-PDAC.

The diagnostic utility of heparin-binding protein among patients with bacterial infections: a systematic review and meta-analysis

BackgroundBacterial infections are considered a leading cause of hospitalization and death globally. There is still a need for a rapid and feasible biomarker for bacterial infections. Heparin-binding protein (HBP) was shown to be related to bacterial infections. The objective of the study is to investigate the diagnostic accuracy of HBP in bacterial infections.MethodsArticles were screened in PubMed, SCOPUS, Web of Science, and Cochrane to recognize eligible studies. We included studies investigating the diagnostic accuracy of HBP and reported the necessary data to construct 2 × 2 tables. A univariate analysis was conducted to determine the pooled sensitivity and specificity, and a bivariate diagnostic random-effects model was used to calculate the optimal cut-off point.ResultsThe analysis comprised sixteen studies in total. Plasma HBP showed a sensitivity of 0.90 (95% CI: [0.79, 0.96]) and a specificity of 0.87 (95% CI: [0.66, 0.96]) in diagnosing bacterial infections using blood samples. Pooling data from seven studies revealed that HBP in cerebrospinal fluid (CSF) has sensitivity and specificity of 96% (95% CI: [0.85, 0.99]), and 95% (95% CI: [0.89, 0.97]), respectively, for the diagnosis of bacterial meningitis. In urinary tract infections (UTI), urine-HBP was revealed to have a high diagnostic value in discriminating bacterial from non-bacterial UTI infection at a cut-off value of 32.868 ng/ml with sensitivity and specificity of 87%.ConclusionHBP has shown a high diagnostic accuracy of bacterial infections, including UTI and meningitis. Further studies are needed to determine its prognostic value and whether it could guide antibiotic therapy.

Evaluation and validation of neutrophil to albumin ratio as a promising prognostic marker for all-cause mortality in patients with cancer: a multicenter cohort study

ObjectivesThe practicality and effectiveness of using the prognostic value of the neutrophil-to-albumin ratio (NAR) in evaluating patients with cancer remain unclear, and research is needed to fully understand its potential application in the cancer population. MethodsThe Kaplan–Meier method was used for survival analysis, and the log-rank test was employed for comparison. Univariate and multivariate Cox proportional hazards models were used to determine the prognostic biomarkers, and Logistic regression analysis was conducted to investigate the relationship between NAR and 90-day outcomes and cachexia. ResultsThe study included 14 682 patients with cancer, divided into discovery (6592 patients), internal validation (2820 patients), and external validation groups (5270 patients). Patients with high NAR had higher all-cause mortality than those with low NAR in the discovery (50.15% versus 69.29%, P < 0.001), internal validation (54.18% versus 70.91%, P < 0.001), and external validation cohorts (40.60% versus 66.68%, P < 0.001). In the discovery cohort, high NAR was observed to be independently associated with all-cause mortality in patients (HR 1.16, 95% CI 1.12–1.19; P < 0.001). Moreover, we validated the promising prognostic value of NAR as a predictor of survival in patients with cancer through internal validation (HR 1.21, 95% CI 1.16–1.27, P < 0.001) and external validation cohorts (HR 1.27, 95% CI 1.21–1.34, P < 0.001). Additionally, in the subgroup analysis by tumor type, high NAR was identified as a risk factor for most cancers, except for breast cancer. ConclusionsThis study showed that NAR is a feasible and promising biomarker for predicting prognosis and cancer cachexia in cancer patients.

Validation of N-Methylpyridinium as a Feasible Biomarker for Roasted Coffee Intake

Health-related nutritional human studies rely on the validity of dietary data provided by study participants. Reliable biomarkers for food intake help objectify data collected by food frequency questionnaires. They facilitate the monitoring of compliance with the study requirements, e.g., abstinence from food, help clean biased data, and remove non-compliant individuals. Biomarker candidates are often revealed by sophisticated metabolomics analyses of body fluids, e.g., urine or plasma, collected from case and control study populations. However, validation for using a biomarker candidate in real-life scenarios is seldomly executed. Coffee is a food item of high interest because of the abundance of bioactive compounds and the regularity of life-time consumption by a large part of the population. Coffee has been found to positively impact cardiovascular risk, type 2 diabetes, and cognitive decline. Coffee and its health implications, therefore, are of high interest. A suitable dietary biomarker for coffee consumption is desirable for the clear classification of study participants as coffee drinkers or non-coffee drinkers to enable correlation of physiological response to dietary habits, e.g., coffee consumption. Here, we propose the roast coffee compound N-methylpyridinium (NMP) as a promising biomarker of pragmatic use to distinguish a coffee drinker from a non-coffee drinker. NMP is an easily accessible analytical target from the plasma and urine matrix that can help determine precedent exposure to roasted coffee products. We review the published information on the coffee compound N-methylpyridinium in foods, coffee, and plasma/urine after coffee consumption, and evaluate the data in the context of the proposed food biomarker criteria “plausibility”, “time- and dose–response”, “robustness”, “reliability”, “stability”, “analytical performance”, and “reproducibility”. An additional data set is acquired to fill the gaps in the literature. In summary, we conclude that the abundance of NMP can serve as a reliable analytical tool to verify recent consumption of roasted coffee. The use of NMP appears limited to being qualitative, as NMP abundance in coffee and human biosamples is affected by several parameters, e.g., the roasting conditions and the volume and time of coffee consumed.