Expert Review of Molecular Diagnostics最新文献

Introduction: Sepsis is a heterogeneous syndrome often misdiagnosed. Point-of-care (POC) diagnostic tests are commonly used to guide decision and include host biomarkers and molecular diagnostics.

Areas covered: The diagnostic and prognostic accuracy of established and emerging biomarkers for sepsis, including procalcitonin (PCT) soluble urokinase plasminogen activator receptor (suPAR), presepsin, TRAIL/IP-10/CRP, MxA, and MxA-CRP, are analyzed in this review. The clinical utility of the two prevalent molecular techniques for pathogens identification using polymerase chain reaction (PCR) assays is also presented: FILMARRAY and QIAstat-Dx RP.

Expert opinion: The rising benefits of the combined use of POC biomarkers with molecular diagnostics in daily clinical routine appear to outperform conventional practices in terms of reduced turnaround time, timely diagnosis, and prompt administration of the appropriate treatment. Yet, this must be further demonstrated in future investigations. However, the cost-effectiveness of POC tests and the high rate of false positive and negative results, indicate the need for a comprehensive clinical evaluation.

Introduction: Sensorineural hearing impairment (SNHI), a common childhood disorder with heterogeneous genetic causes, can lead to delayed language development and psychosocial problems. Next-generation sequencing (NGS) offers high-throughput screening and high-sensitivity detection of genetic etiologies of SNHI, enabling clinicians to make informed medical decisions, provide tailored treatments, and improve prognostic outcomes.

Areas covered: This review covers the diverse etiologies of HHI and the utility of different NGS modalities (targeted sequencing and whole exome/genome sequencing), and includes HHI-related studies on newborn screening, genetic counseling, prognostic prediction, and personalized treatment. Challenges such as the trade-off between cost and diagnostic yield, detection of structural variants, and exploration of the non-coding genome are also highlighted.

Expert opinion: In the current landscape of NGS-based diagnostics for HHI, there are both challenges (e.g. detection of structural variants and non-coding genome variants) and opportunities (e.g. the emergence of medical artificial intelligence tools). The authors advocate the use of technological advances such as long-read sequencing for structural variant detection, multi-omics analysis for non-coding variant exploration, and medical artificial intelligence for pathogenicity assessment and outcome prediction. By integrating these innovations into clinical practice, precision medicine in the diagnosis and management of HHI can be further improved.

Introduction: Inborn errors of immunity (IEIs) refer to a heterogeneous category of diseases with defects in the number and/or function of components of the immune system. Immunoglobulin A (IgA) deficiency is the most prevalent IEI characterized by low serum level of IgA and normal serum levels of IgG and/or IgM. Most of the individuals with IgA deficiency are asymptomatic and are only identified through routine laboratory tests. Others may experience a wide range of clinical features including mucosal infections, allergies, and malignancies as the most important features. IgA deficiency is a multi-complex disease, and the exact pathogenesis of it is still unknown.

Areas covered: This review compiles recent research on genetic and epigenetic factors that may contribute to the development of IgA deficiency. These factors include defects in B-cell development, IgA class switch recombination, synthesis, secretion, and the long-term survival of IgA switched memory B cells and plasma cells.

Expert opinion: A better and more comprehensive understanding of the cellular pathways involved in IgA deficiency could lead to personalized surveillance and potentially curative strategies for affected patients, especially those with severe symptoms.

Introduction: Diabetic microvascular complications such as retinopathy, nephropathy, and neuropathy are primary causes of blindness, terminal renal failure, and neuropathic disorders in type 2 diabetes mellitus patients. Identifying reliable biomarkers promptly is pivotal for early detection and intervention in these severe complications.

Areas covered: This review offers a thorough examination of the latest research concerning serum biomarkers for the prediction and assessment of diabetic microvascular complications. It encompasses biomarkers associated with glycation, oxidative stress, inflammation, endothelial dysfunction, basement membrane thickening, angiogenesis, and thrombosis. The review also highlights the potential of emerging biomarkers, such as microRNAs and long non-coding RNAs.

Expert opinion: Serum biomarkers are emerging as valuable tools for the early assessment and therapeutic guidance of diabetic microvascular complications. The biomarkers identified not only reflect the underlying pathophysiology but also align with the extent of the disease. However, further validation across diverse populations and improvement of the practicality of these biomarkers in routine clinical practice are necessary. Pursuing these objectives is essential to advance early diagnosis, risk assessment, and individualized treatment regimens for those affected by diabetes.

Introduction: Young onset dementia (YOD) by its nature is difficult to diagnose. Despite involvement of multidisciplinary neurogenetics services, patients with YOD and their families face significant diagnostic delays. Genetic testing for people with YOD currently involves a staggered, iterative approach. There is currently no optimal single genetic investigation that simultaneously identifies the different genetic variants resulting in YOD.

Areas covered: This review discusses the advances in clinical genomic testing for people with YOD. Whole genome sequencing (WGS) can be employed as a 'one stop shop' genomic test for YOD. In addition to single nucleotide variants, WGS can reliably detect structural variants, short tandem repeat expansions, mitochondrial genetic variants as well as capture single nucleotide polymorphisms for the calculation of polygenic risk scores.

Expert opinion: WGS, when used as the initial genetic test, can enhance the likelihood of a precision diagnosis and curtail the time taken to reach this. Finding a clinical diagnosis using WGS can reduce invasive and expensive investigations and could be cost effective. These advances need to be balanced against the limitations of the technology and the genetic counseling needs for these vulnerable patients and their families.

Introduction: In older adults, where sleep disturbances and cognitive impairment are common, mounting evidence suggests a potential connection between sleep and cognitive function, highlighting the significance of utilizing sleep as a biomarker for early detection of cognitive impairment to improve clinical outcomes in a noninvasive, cost-effective manner.

Areas covered: This review describes the relationship between sleep and cognitive function in older adults, encompassing both subjective and objective measures of sleep quality, duration, architecture, and sleep-disordered breathing. The authors consider the directionality of the associations observed in prospective and cross-sectional studies, exploring whether sleep disturbances precede cognitive decline or vice versa. Furthermore, they discuss the potential bidirectional relationships between sleep and Alzheimer's disease (AD) risks in older adults while also examining the neurodegenerative pathways of this relationship.

Expert opinion: Routine sleep monitoring in primary care settings has the potential to bolster early detection and treatment of sleep disturbance, and by extension, reduce the risk of dementia. Improving sleep assessment tools, such as wearables, provide scalable alternatives to traditional methods like polysomnography, potentially enabling widespread monitoring of sleep characteristics. Standardized measurement and inclusive participant recruitment are needed to enhance generalizability, while longitudinal studies are essential to understand the interaction between sleep and AD pathology.

Background: The expression of CYP19A1 has implications for the prognosis of female bladder cancer. However, this study aimed to explore the association between single nucleotide polymorphisms (SNPs) in CYP19A1 and bladder cancer risk, as no prior research has addressed this association.

Research design and methods: We selected and genotyped five CYP19A1 SNPs (rs4646, rs6493487, rs1062033, rs17601876, and rs3751599) in 217 patients and 550 controls using the Agena MassARRAY system. Logistic regression analysis was employed to calculate the odds ratio (OR) and 95% confidence intervals (CIs). Bioinformatics predicted SNP functions and CYP19A1 involving pathways.

Results: Our study revealed a significant association between bladder cancer risk and four SNPs (rs4646 (AC vs. CC: OR = 1.71, FDR-p = 0.005), rs6493487 (G vs. A: OR = 0.68, FDR-p = 0.011), rs1062033 (G vs. C: OR = 0.36, FDR-p < 0.001), and rs17601876 (GA vs. GG: OR = 1.66, FDR-p = 0.008)) in CYP19A1. The three SNPs (rs4646, rs1062033, and rs17601876) were significantly correlated with CYP19A1 expression levels in normal whole blood (p < 0.05). Moreover, CYP19A1 was found to primarily participate in the steroid hormone biosynthesis and metabolic pathways.

Conclusions: Consequently, CYP19A1 gene polymorphisms may play a crucial role in the genetic susceptibility to bladder cancer.

Introduction: Colon cancer, ranked as the fourth leading global cause of cancer death, exhibits a complex progression marked by genetic variations. Over the past decade, the utilization of diverse CRISPR systems has propelled accelerated research into colorectal cancer (CRC) treatment.

Areas covered: CRISPR/Cas9, a key player in this research, identifies new oncogenes, tumor suppressor genes (TSGs), and drug-resistance genes. Additionally, it facilitates the construction of experimental models, conducts genome-wide library screening, and develops new therapeutic targets, especially for targeted knockout in vivo or molecular targeted drug delivery, contributing to personalized treatments and significantly enhancing the care of colon cancer patients. In this review, we provide insights into the mechanism of the CRISPR/Cas9 system, offering a comprehensive exploration of its applications in CRC, spanning screening, modeling, gene functions, diagnosis, and gene therapy. While acknowledging its transformative potential, the article  highlights the challenges and limitations of CRISPR systems.

Expert opinion: The application of CRISPR/Cas9 in CRC research provides a promising avenue for personalized treatments. Its potential for identifying key genes and enabling experimental models and genome-wide screening enhances patient care. This review underscores the significance of CRISPR-Cas9 gene editing technology across basic research, diagnosis, and the treatment landscape of colon cancer.

Introduction: Community-acquired pneumonia (CAP) is an infectious disease associated with high mortality worldwide. Although Streptococcus pneumoniae remains the most frequent pathogen in CAP, data from recent studies using molecular tests have shown that respiratory viruses play a key role in adults with pneumonia. The impact of difficult-to-treat pathogens on the outcomes of pneumonia is also important even though they represent only a small proportion of overall cases. Despite improvements in the microbiological diagnosis of CAP in recent decades, the identification of the causative pathogen is often delayed because of difficulties in obtaining good-quality sputum samples, issues in transporting samples, and slow laboratory processes. Therefore, the initial treatment of CAP is usually empirical. Point-of-care testing (POCT) was introduced to avoid treatment delays and reduce reliance on empirical antibiotics.

Areas covered: This review summarizes the main scientific evidence on the role of POCT in the diagnosis and management of patients with CAP. The authors searched for articles on POCT in pneumonia on PubMed from inception to 20 January 2024. The references in the identified articles were also searched.

Expert opinion: POCT involves rapid diagnostic assays that can be performed at the bedside especially in cases of severe CAP and immunocompromised patients. These tests can produce results that could help guide initial therapy and management.

Introduction: Acute kidney injury (AKI) defined by a substantial decrease in kidney function within hours to days and is often irreversible with higher risk to chronic kidney disease (CKD) transition.

Areas covered: The authors discuss the diagnostic and predictive utilities of serum and urinary biomarkers on AKI and on the risk of AKI-to-CKD progression. The authors focus on the relevant literature covering evidence of circulating and urinary biomarkers' capability to predict the transition of AKI to CKD.

Expert opinion: Based on the different modalities of serum and urinary biomarkers, multiple biomarker panel seems to be potentially useful to distinguish between various types of AKI, to detect the severity and the risk of AKI progression, to predict the clinical outcome and evaluate response to the therapy. Serum/urinary neutrophil gelatinase-associated lipocalin (NGAL), serum/urinary uromodulin, serum extracellular high mobility group box-1 (HMGB-1), serum cystatin C and urinary liver-type fatty acid-binding protein (L-FABP) were the most effective in the prediction of AKI-to-CKD transition regardless of etiology and the presence of critical state in patients. The current clinical evidence on the risk assessments of AKI progression is mainly based on the utility of combination of functional, injury and stress biomarkers, mainly NGAL, L-FABP, HMGB-1 and cystatin C.