Expert Review of Molecular Diagnostics最新文献

Introduction: Early diagnosis and treatment initiation are essential to prevent ongoing tuberculosis (TB) transmission and reduce the disease burden. Smear microscopy, which is widely used test for diagnosis, has limited sensitivity and does not detect rifampicin resistance. Truenat is a portable, battery-operated, chip-based test that can be placed in peripheral laboratories, serving as a point-of-care test. It also detects rifampicin resistance, which is crucial in the management of TB.

Areas covered: Our review comprehensively covers the functionality and workflow of the Truenat MTB assay, in addition to its cost-effectiveness and diagnostic accuracy, based on recent evidence. We also discuss the merits and drawbacks of alternative diagnostic tests available for detecting TB and rifampicin resistance.

Expert opinion: Truenat assays are rapid molecular tests that revolutionized TB diagnosis, moving toward peripheral testing. Evidence indicates that the Truenat MTB Plus performs better than the original Truenat MTB, with an approximate LOD of 30 CFU/ml. The 2025 WHO guidelines rely exclusively on data from Truenat MTB Plus. We need larger studies on the newer Truenat MTB Ultima to evaluate its performance on tongue swabs. Additionally, data on the accuracy of Truenat MTB in children remains scarce, emphasizing the importance of further research in this group. Evidence regarding its accuracy in detecting rifampicin resistance is also limited, requiring larger studies and technological advancements. Truenat MTB will remain crucial in the fight to eliminate TB in the future.

Introduction: Infections caused by different Leishmania species are considered as neglected diseases and are prevalent in many tropical and temperate regions worldwide. Extracellular vehicles (EVs) transport different nanoparticles for extracellular medium as enzymes, proteins, lipids, nucleic acids and others for cellular metabolic activities. However, the precise role of EVs in infections caused by Leishmania species is not totally established. This article revised the significance of EVs in pathogenesis, diagnosis and treatment strategies for the different forms of leishmaniasis.

Areas covered: EVs of Leishmania spp. may be considered as potential drug targets in treatment, as they can encapsulate small molecules or drugs for more effective delivery to specific cells or tissues. The perspectives on EVs research in Leishmania facilitate the understanding of the role of these nanoparticles in parasite-host interactions and the development of diagnostic and therapeutic strategies, as vaccine development, and enhancing drug delivery systems.

Expert opinion: The knowledge of the participation of EVs in Leishmania species offers opportunities to further our understanding in pathogenesis and in the development of innovative diagnostic tools and treatments and to explore new approaches to disease.

Introduction: Bladder cancer (BC) is a prevalent urinary tract malignancy, characterized by high recurrence rates and heterogeneous disease progression. Non-muscle invasive bladder cancer (NMIBC) and muscle-invasive bladder cancer (MIBC) present distinct clinical challenges, and conventional clinicopathological parameters are often insufficient to predict recurrence or progression accurately. Long non-coding RNAs (lncRNAs) have emerged as key regulators of tumor biology, influencing proliferation, migration, epithelial-mesenchymal transition, and therapy resistance, with potential in risk stratification, prognostic prediction and guidance of therapy de-escalation or intensification.

Areas covered: This narrative review examines the role of lncRNAs in BC, focusing on their biological functions, prognostic significance, and potential to guide personalized treatment strategies. We discuss lncRNA involvement in NMIBC and MIBC, highlight molecular profiling studies enabling risk stratification and molecular subtyping for guiding treatment de-escalation or intensification. Finally, we address the challenges and future directions for integrating lncRNA profiling into routine clinical practice.

Expert opinion: LncRNAs offer a promising approach for precision oncology in bladder cancer, providing insights beyond traditional clinical parameters. Integrating lncRNA profiling into routine practice could optimize risk stratification, guide therapy intensity, and reduce overtreatment. Although current evidence is encouraging, large-scale prospective trials are needed to validate lncRNA signatures and fully realize their potential in personalized bladder cancer management.

Introduction: Ovarian cancer is a leading cause of cancer-related death in women, primarily due to nonspecific symptoms and diagnosis at an advanced stage. Improving outcomes through earlier diagnosis and effective population screening remains a global priority.

Context: Existing modalities ,including CA125 and transvaginal ultrasound (TVUS), lack sufficient specificity and sensitivity, and no screening strategy has demonstrated a reduction in mortality. Multivariate Index Assays (MIAs), that combine multiple biomarker results into a single risk score, have emerged as a promising approach for differential diagnosis of adnexal masses, early detection, and screening.

Areas covered: This review summarizes current literature and clinical trial data on MIAs in ovarian cancer, describing their advantages over single biomarkers, their potential to improve patient outcomes, and their role in personalized medicin. Successful clinical adoption of MIAs will depend on well-designed prospective studies that robustly validate their clinical utility.

Expert opinion/commentary: It is also critical to clearly distinguish between diagnostic and screening applications, as each requires different performance characteristics, regulatory pathways, and target populations, and no ovarian cancer screening test is currently approved for routine use.

Introduction: MUC4 is overexpressed in gastric cancer and its precursor lesions and plays an essential role in disease progression.

Area covered: In this review, we describe the diagnostic and prognostic value of MUC4 expression in gastric cancer. First, we provide a summary of gastric cancer pathogenesis and its intricate relationship with mucin expression. We will then provide an extensive description of MUC4 expression in gastric cancer and its diagnostic and therapeutic significance.

Expert opinion: Apart from its protective role in normal physiology, MUC4 contributes to disease progression and metastasis in several malignancies, including gastric cancer. MUC4 is expressed at negligible levels in normal gastric mucosa. However, some patients with intestinal metaplasia and gastric cancer have high levels of MUC4 expression, particularly in the pit cell compartment. The expression of MUC4 in metaplastic pit cells is associated with increased proliferation, inflammation, and epithelial-to-mesenchymal transition. Hence, evaluating MUC4 expression in precursor lesions may help stratify disease and identify cases in which curative surgery should be performed. MUC4 expression in gastric cancer is associated with disease aggressiveness, lymphatic invasion, and nodal metastasis. Due to its role in disease pathobiology, it is a promising target for the diagnosis and therapy of gastric cancer.

Introduction: Sepsis, a life-threatening condition characterized by dysregulated host immune and metabolic responses to infection, is associated with high mortality, making accurate diagnosis and targeted treatment crucial. Sepsis often induces a notable reduction in serum high-density lipoprotein (HDL) levels. As the fundamental structural and functional components of HDL, apolipoproteins play pivotal roles in mediating the function of HDL. Therefore, these apolipoproteins can serve as potential biomarkers in sepsis.

Areas covered: This review systematically synthesizes current evidence on the dynamic expression profiles of these apolipoproteins in sepsis, highlighting the relation of their single nucleotide polymorphisms (SNPs) with sepsis and clinical relevance in diagnosis and prognosis. Furthermore, it also summarizes the underlying mechanisms by which these apolipoproteins are involved in the progression of sepsis.

Expert opinion: The changes in the levels of HDL-associated apolipoproteins can characterize the progression of sepsis and the type of infecting bacteria, and provide therapeutic targets for the treatment of sepsis. Therefore, the comprehensive understanding of their integrated effects holds promise for developing precision interventions to improve clinical outcomes of sepsis.

Background: Intrinsic capacity (IC) decline is a key marker of aging-related functional loss, yet sex-specific biomarkers remain poorly characterized. This cross-sectional study of 1014 community-dwelling older adults investigated the associative strength and potential statistical intermediaries of insulin-like growth factor binding protein 2 (IGFBP2) and growth differentiation factor 15 (GDF-15) in IC impairment, with sex-stratified analyses.

Research design and methods: Dose-response relationships were assessed using restricted cubic splines. Multivariable logistic regression evaluated independent associations after adjusting for covariates. Mediation analysis explored roles of renal, muscular, metabolic, and oxidative stress indicators.

Results: IC impairment was associated with higher IGFBP2 and GDF-15 (all p < 0.001). In males, IGFBP2 showed a reverse L-shaped association (inflection at 310 ng/mL; AUC = 0.75), partially explained by renal function (β2-MG), muscle damage (CK, LDH), oxidative stress (SOD), and nutrition (ALB), with 11.02% mediation. In females, GDF-15 had a nonlinear relationship (inflection at 1.99 ng/mL; AUC = 0.76), attributable in part to glucose (FBG), lipids (FFA), and renal function (BUN), accounting for 19.8% of the effect. Fully adjusted ORs were 2.41 (IGFBP2 in males) and 4.27 (GDF-15 in females), both p < 0.001.

Conclusion: IGFBP2 and GDF-15 are sex-specific biomarkers for IC decline, operating through distinct pathways, and may aid early screening and targeted interventions.

Background: Critically ill patients have high mortality influenced by insulin resistance (IR)and inflammation.The C-reactive protein-triglyceride-glucose index (CTI), integrating IR and inflammation, has unclear prognostic value in this population compared to the traditional triglyceride-glucose index (TyG).

Methods: This cohort study analyzed 1963 critically ill patients from MIMIC-IV. Outcomes included in-hospital mortality, acute kidney injury (AKI), and length of stay. Analyses employed multivariable regression, mediation, and machine learning.

Results: Elevated CTI showed a graded association with mortality. Per unit increase conferred 22% higher risk (OR 1.22, 95% CI 1.08-1.38); the top quartile had double the risk (OR 2.07, 1.36-3.13) and a mortality rate of 26.48% vs. 9.98% in the lowest quartile. CTI also independently predicted higher AKI risk (OR 1.28, 1.13-1.45; incidence 91.24% vs. 73.32% in Q4 vs. Q1) and prolonged ICU/hospital stay (β 1.99 and 3.71 days, p < 0.05). AKI mediated 5.53% of the CTI-mortality relationship. CTI's discriminative power surpassed TyG (DeLong p = 0.001). In prognostic modeling, CTI was a key feature, with the Gradient Boosting Machine model achieving optimal performance (AUC 0.789).

Conclusion: CTI is strongly associated with adverse outcomes and may outperform TyG in critically ill patients, supporting its utility for risk stratification.