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BMC Nephrology May 2024Recent studies have suggested that the N-terminal fragment of B-type natriuretic peptide (NT-proBNP) level serve as a significant risk factor for mortality in patients...
BACKGROUND
Recent studies have suggested that the N-terminal fragment of B-type natriuretic peptide (NT-proBNP) level serve as a significant risk factor for mortality in patients with end-stage renal disease. However, the relationship between NT-proBNP levels and technique failure in peritoneal dialysis-associated peritonitis (PDAP) remains unclear. This study investigated the relationship between NT-proBNP levels at the onset of PDAP and the risk of technique failure in patients with PDAP.
METHODS
A retrospective analysis was conducted on patients with PDAP from December 1, 2009, to December 31, 2021, at our peritoneal dialysis center. We recorded all demographic and baseline clinical data at the time of admission for each PDAP episode. Logistic and Cox regression analyses were performed to assess the association between NT-proBNP levels and technique failure.
RESULTS
Of 485 PDAP episodes included in this study, 130 episodes of technique failure were observed. Multivariate logistic analysis revealed that hospital stay, Na and NT-proBNP levels, and peritoneal dialysate white blood cell counts on days 3 and 5 were independently associated with technique failure. The receiver operating characteristic curve demonstrated that the NT-proBNP level was a better indicator than the other four variables in indicating technique failure. In the multivariate Cox regression analysis, after adjusting for confounding factors, higher NT-proBNP levels (HR of 3.020, 95% CI 1.771, 5.150, P < 0.001) were associated with PDAP technique failure.
CONCLUSIONS
This retrospective study identified the serum NT-proBNP level at the onset of PDAP as an independent risk factor for technique failure in these patients.
Topics: Humans; Natriuretic Peptide, Brain; Male; Female; Peritoneal Dialysis; Peptide Fragments; Middle Aged; Peritonitis; Retrospective Studies; Risk Factors; Kidney Failure, Chronic; Treatment Failure; Aged; Adult; Biomarkers
PubMed: 38760707
DOI: 10.1186/s12882-024-03603-0 -
Cancer Control : Journal of the Moffitt... 2024
Topics: Humans; Head and Neck Neoplasms; Periodontal Diseases; Radiotherapy; Radiation Injuries
PubMed: 38760005
DOI: 10.1177/10732748241255845 -
Asian Journal of Andrology May 2024Discovery of spermatozoa during the 17th century led to developing technologies for semen analysis in the early 1900s, and then, standard techniques were implemented...
Discovery of spermatozoa during the 17th century led to developing technologies for semen analysis in the early 1900s, and then, standard techniques were implemented during the 20th century. Semen analysis has a pivotal role in the male infertility evaluation, and azoospermia is an important finding. Azoospermia is identified in 15% of infertile men. However, the accurate laboratory assessment of azoospermia poses certain technical challenges. Laboratories currently perform semen assessment with great variability; thus, a standard method should be used. Planning suitable management and determining the cause of infertility require a precise evaluation of azoospermia. This review aims to address the definition of azoospermia and highlight laboratory methods in the assessments of azoospermia. Basic methods such as centrifugation, repeat pellet analysis, and staining and advanced methods such as genetic testing and biomarkers have been discussed. These methods have helped in standardizing the protocol for accurate azoospermia assessments with less variability.
PubMed: 38759095
DOI: 10.4103/aja202429 -
PloS One 2024We have previously shown that polygenic risk scores (PRS) can improve risk stratification of peripheral artery disease (PAD) in a large, retrospective cohort. Here, we...
We have previously shown that polygenic risk scores (PRS) can improve risk stratification of peripheral artery disease (PAD) in a large, retrospective cohort. Here, we evaluate the potential of PRS in improving the detection of PAD and prediction of major adverse cardiovascular and cerebrovascular events (MACCE) and adverse events (AE) in an institutional patient cohort. We created a cohort of 278 patients (52 cases and 226 controls) and fit a PAD-specific PRS based on the weighted sum of risk alleles. We built traditional clinical risk models and machine learning (ML) models using clinical and genetic variables to detect PAD, MACCE, and AE. The models' performances were measured using the area under the curve (AUC), net reclassification index (NRI), integrated discrimination improvement (IDI), and Brier score. We also evaluated the clinical utility of our PAD model using decision curve analysis (DCA). We found a modest, but not statistically significant improvement in the PAD detection model's performance with the inclusion of PRS from 0.902 (95% CI: 0.846-0.957) (clinical variables only) to 0.909 (95% CI: 0.856-0.961) (clinical variables with PRS). The PRS inclusion significantly improved risk re-classification of PAD with an NRI of 0.07 (95% CI: 0.002-0.137), p = 0.04. For our ML model predicting MACCE, the addition of PRS did not significantly improve the AUC, however, NRI analysis demonstrated significant improvement in risk re-classification (p = 2e-05). Decision curve analysis showed higher net benefit of our combined PRS-clinical model across all thresholds of PAD detection. Including PRS to a clinical PAD-risk model was associated with improvement in risk stratification and clinical utility, although we did not see a significant change in AUC. This result underscores the potential clinical utility of incorporating PRS data into clinical risk models for prevalent PAD and the need for use of evaluation metrics that can discern the clinical impact of using new biomarkers in smaller populations.
Topics: Humans; Peripheral Arterial Disease; Female; Male; Aged; Middle Aged; Risk Assessment; Risk Factors; Machine Learning; Cardiovascular Diseases; Retrospective Studies; Multifactorial Inheritance; Case-Control Studies; Area Under Curve; Genetic Risk Score
PubMed: 38758931
DOI: 10.1371/journal.pone.0303610 -
PloS One 2024Collection of biosamples for translational research studies is vital for understanding biological pathways, discovering disease-related biomarkers, and identifying novel...
BACKGROUND AND OBJECTIVE
Collection of biosamples for translational research studies is vital for understanding biological pathways, discovering disease-related biomarkers, and identifying novel therapeutic targets. However, a lack of infrastructure for sample procurement, processing, storage, and shipping may hinder the ability of clinical research units to effectively engage in translational research. The purpose of this study was to identify the barriers to biosampling-based translational research in the critical care setting in Canada.
METHODS
We administered an online survey to members of the Canadian Critical Care Trials Group (CCCTG), the Canadian Critical Care Translational Biology Group (CCCTBG), and the Canadian Critical Care Research Coordinators Group (CCCRCG). The survey focused on participants' personal experience of biosampling research, research infrastructure, motivating factors, and perceived barriers.
RESULTS
We received 59 responses from 31 sites, including 6 community intensive care unit (ICU) sites. The overall response rate was 11.3%. The majority of respondents were research coordinators (44%), followed by clinician-investigators (33.8%), graduate students (10.2%), and PhD-investigators (8.5%). Although most (63.8%) respondents reported an interest in participating in translational research, they also reported that their ICUs were currently contributing to a third of the number of translational studies compared to clinical studies. For respondents with experience in participating in translational research studies, the most common barriers were lack of funding, lack of time, and insufficient research staff. For respondents without previous experience, the perceived facilitators were more interest from their research group, improved training/mentorship, increased funding, and better access to laboratory equipment.
CONCLUSIONS
Our survey found that the majority of participants were interested in and recognize the value of participating in biosampling-based translational research but lacked funding, time, and research personnel trained in biosampling protocols. Our survey also identified factors that might encourage participation at new sites. Addressing these barriers will be a key step towards increasing translational research capacity across Canada.
Topics: Humans; Translational Research, Biomedical; Canada; Critical Care; Cross-Sectional Studies; Surveys and Questionnaires; Research Personnel; Male; Female; Specimen Handling
PubMed: 38758919
DOI: 10.1371/journal.pone.0303304 -
Medicine May 2024The inflammatory and nutritional states of body are 2 important causes associated with the initiation and progression of colorectal cancer (CRC). The aim of this study... (Observational Study)
Observational Study
The inflammatory and nutritional states of body are 2 important causes associated with the initiation and progression of colorectal cancer (CRC). The aim of this study is to investigate the prognostic evaluation value of preoperative fibrinogen-to-prealbumin ratio (FPR) and preoperative fibrinogen-to-albumin ratio (FAR) in CRC. The clinical data of 350 stages II and III patients with CRC who received radical resection were retrospectively analyzed. All patients were followed up for 5 years to observe the overall survival and disease-free survival of 5 years and analyze the relationship between preoperative FPR and FAR and prognosis of all enrolled patients. In addition, we analyzed the diagnostic and application value of combined biomarkers. This study showed high-level preoperative FPR and FAR were significantly associated with poor overall survival and disease-free survival of stages II and III patients with CRC. The elevated preoperative FPR and FAR level was significantly related to age, tumor differentiation level, TNM stage, vascular infiltration, carcinoembryonic antigen, carbohydrate antigen199, etc. The combination of FPR, FAR, neutrophil-to-lymphocyte ratio, and carbohydrate antigen199 had the maximum area under curve (AUC = 0.856, 95% CI: 0.814-0.897, Sen = 78.20%, Spe = 82.49%, P < .05) under the receiver-operating characteristics curve. The preoperative FPR and FAR have important prognostic value and they can be used as independent prognostic marker for patients with stages II and III CRC undergoing radical resection. Moreover, the combination of biomarkers could further enhance the diagnostic and prognostic efficacy of CRC.
Topics: Humans; Colorectal Neoplasms; Male; Retrospective Studies; Female; Middle Aged; Prognosis; Neoplasm Staging; Aged; Fibrinogen; Biomarkers, Tumor; Preoperative Period; Serum Albumin; Adult; Disease-Free Survival
PubMed: 38758911
DOI: 10.1097/MD.0000000000038145 -
Medicine May 2024Previous studies have revealed the critical functions of NEK2 in controlling the cell cycle which is linked to poor prognosis in multiple tumor types, but less research...
BACKGROUND
Previous studies have revealed the critical functions of NEK2 in controlling the cell cycle which is linked to poor prognosis in multiple tumor types, but less research has been devoted to clear cell renal cell carcinoma (ccRCC).
METHODS
We downloaded clinical data from the gene expression omnibus (GEO) and TCGA databases together with transcriptional and mutational datasets. Strongly coexpressed genes with NEK2 were extracted from TCGA-KIRC cohort, and were submitted to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) for functional analyses. According to NEK2 levels, the survival status, mutational characteristics, response to immunotherapy and sensitivity to drugs of the patients were studied. The potential correlations between NEK2 levels and immune cell state as well as immune cell infiltration were examined using the GEPIA, TIMER and TISIDB databases. Double immunofluorescence (IF) was performed to identify the NEK2 overexpression and relationship with CD8 in ccRCC.
RESULTS
The NEK2 gene was overexpressed and would enhance the nuclear division and cell cycle activities in ccRCC. ccRCC patients with high NEK2 expression had worse clinical outcomes, higher mutation burden and better therapeutic response. Moreover, NEK2 gene overexpression was positively related to various immune cell marker sets, which was also proved by validation cohort, and more infiltration of various immune cells.
CONCLUSION
ccRCC patients with NEK2 high expression have a poorer prognosis than those with NEK2 low expression, resulting from its function of promoting proliferation, accompanied by increased infiltration of CD8 + T cells and Tregs and T-cell exhaustion and will respond better to proper treatments.
Topics: Humans; Carcinoma, Renal Cell; NIMA-Related Kinases; Kidney Neoplasms; Tumor Microenvironment; Prognosis; Male; Gene Expression Regulation, Neoplastic; Female; Mutation; Biomarkers, Tumor; Databases, Genetic
PubMed: 38758909
DOI: 10.1097/MD.0000000000037939 -
Medicine May 2024Human immunodeficiency virus (HIV) infection continues to pose significant global health challenges, necessitating advancements in diagnostic and prognostic approaches... (Review)
Review
Human immunodeficiency virus (HIV) infection continues to pose significant global health challenges, necessitating advancements in diagnostic and prognostic approaches to optimize disease management. While primarily recognized for their roles in allergic responses, mast cells have emerged as potential markers with diagnostic and prognostic significance in the context of HIV/AIDS. This paper aims to synthesize current insights and delineate future directions regarding the utility of mast cell markers in diagnosing HIV infection, predicting disease progression, and guiding therapeutic strategies. Mast cells, equipped with distinct markers such as tryptase, chymase, carboxypeptidase A3, and c-kit/CD117 receptors, exhibit tissue-specific expression patterns that offer potential as diagnostic indicators for HIV infection. Understanding the dynamics of these markers in different tissues and body fluids holds promise for accurate HIV diagnosis, disease staging, and monitoring treatment responses. Moreover, the prognostic significance of mast cell markers in HIV/AIDS lies in their potential to predict disease progression, immune dysregulation, and clinical outcomes. The integration of mast cell markers into clinical applications offers promising avenues for refining diagnostic assays, patient monitoring protocols, and therapeutic strategies in HIV/AIDS. Future research directions involve the development of novel diagnostic tools and targeted therapies based on mast cell-specific markers, potentially revolutionizing clinical practice and enhancing patient care in the management of HIV/AIDS. Continued investigations into mast cell markers' diagnostic and prognostic implications hold immense potential to advance our understanding and improve outcomes in HIV/AIDS management.
Topics: Humans; Mast Cells; Biomarkers; Prognosis; HIV Infections; Tryptases; Disease Progression; Carboxypeptidases A; Chymases; Proto-Oncogene Proteins c-kit; Acquired Immunodeficiency Syndrome
PubMed: 38758896
DOI: 10.1097/MD.0000000000038117 -
Medicine May 2024Atherosclerosis (AS), as a complex chronic inflammatory disease, is 1 of the main causes of cardiovascular and cerebrovascular diseases. This study aimed to confirm the...
BACKGROUND
Atherosclerosis (AS), as a complex chronic inflammatory disease, is 1 of the main causes of cardiovascular and cerebrovascular diseases. This study aimed to confirm the direct interaction between miR-146a-3p and NF-κB, and explore the role of miR-146a-3p/NF-κB in the regulation of inflammation in AS.
METHODS
Bioinformatic prediction and dual-luciferase reporter assay were used to confirm the interaction between miR-146a-3p and NF-κB. Lipopolysaccharides stimulation was performed to establish AS inflammatory cell model, and the levels of pro-inflammatory cytokines were estimated using an enzyme-linked immunosorbent assay. miR-146a-3p and NF-κB expression were evaluated using reverse transcription quantitative PCR, and their clinical value was examined using a receiver operating characteristic curve.
RESULTS
Inflammatory cell model showed increased IL-1β, IL-6, and TNF-α. NF-κB was a target gene of miR-146a-3p, and mediated the inhibitory effects of miR-146a-3p on inflammatory responses in the cell model. In patients with AS, miR-146a-3p/NF-κB was associated with patients' clinical data and inflammatory cytokine levels, and aberrant miR-146a-3p and NF-κB showed diagnostic accuracy to distinguish AS patients from healthy populations.
CONCLUSION
miR-146a-3p might inhibit inflammation by targeting NF-κB in AS progression, and miR-146a-3p/ NF-κB might provide novel biomarkers and therapeutic targets for the prevention of AS and related vascular events.
Topics: MicroRNAs; Humans; Atherosclerosis; NF-kappa B; Disease Progression; Male; Cytokines; Female; Inflammation; Middle Aged; Lipopolysaccharides
PubMed: 38758895
DOI: 10.1097/MD.0000000000038061 -
Medicine May 2024Therapy resistance in gastric cancer poses ongoing challenges, necessitating the identification of ferroptosis-related genes linked to overall survival for potential...
Therapy resistance in gastric cancer poses ongoing challenges, necessitating the identification of ferroptosis-related genes linked to overall survival for potential therapeutic insights. The purpose of the study was to identify ferroptosis-related genes contributing to therapy resistance in gastric cancer and explore their associations with overall survival. Differentially expressed ferroptosis-related genes were identified in therapy-resistant versus therapy-responsive gastric cancer patients. Hub genes were selected from these genes. Enrichment analysis focused on oxidative stress and ROS metabolism. Validation was conducted in a TCGA stomach adenocarcinoma dataset. A hub gene-based risk model (DUSP1/TNF/NOX4/LONP1) was constructed and assessed for overall survival prediction. Associations with the tumor immune microenvironment were examined using the ESTIMATE algorithm and correlation analysis. Ten hub genes were identified, enriched in oxidative stress and ROS metabolism. Validation confirmed their aberrant expressions in the TCGA dataset. The hub gene-based risk model effectively predicted overall survival. High G6PD/TNF expression and low NOX4/SREBF1/MAPK3/DUSP1/KRAS/SIRT3/LONP1 expression correlated with stromal and immune scores. KRAS/TNF/MAPK3 expression positively correlated with immune-related SREBF1/NOX4 expression. DUSP1/NOX4/SREBF1/TNF/KRAS expression was associated with immune cell infiltration. The hub gene-based risk model (DUSP1/TNF/NOX4/LONP1) shows promise as an overall survival predictor in gastric cancer. Ferroptosis-related hub genes represent potential therapeutic targets for overcoming therapy resistance in gastric cancer treatment.
Topics: Stomach Neoplasms; Humans; Ferroptosis; Drug Resistance, Neoplasm; Tumor Microenvironment; Gene Expression Regulation, Neoplastic; Oxidative Stress; Male; Reactive Oxygen Species; Biomarkers, Tumor
PubMed: 38758860
DOI: 10.1097/MD.0000000000038193