Expert Review of Molecular Diagnostics最新文献

Introduction: Currently the diagnosis of Kawasaki disease is still heavily reliant on clinical criteria which may be subject to interpretation or mimic other common febrile diseases of childhood. Biomarkers that can aid in the accurate and timely diagnosis of KD are of great clinical utility.

Areas covered: A literature search of PubMed was performed using the key words: Kawasaki disease, diagnosis, biomarkers, proteomics and transcriptomics. In this article we review biomarkers that are widely clinically available including NT-ProBNP and ferritin. We also include promising novel biomarkers that have been identified through newer transcriptomic and proteomic techniques.

Expert opinion: While the identification of biomarkers that can accurately assist in diagnosing patients with KD is a promising field of research, more still remains to be done to in order to validate new biomarkers in larger cohorts, and to set standardized cutoff values for potential biomarkers that are currently clinically available. Further research is needed before KD biomarkers that are consistent, readily available and cost-effective can be a clinical reality.

Introduction: While Pneumocystis pneumonia (PcP) remains a major AIDS-defining disease, the majority of cases of PcP now present in the HIV-negative cohort, causing significant mortality. PcP PCR diagnosis is not novel, and the optimal route of diagnosis remains unclear, with an imperfect reference method and complexity in result interpretation for alternative tests.

Areas covered: This extensive review utilizing a literature search underpinning a recent systematic review/meta-analysis discusses the technical and clinical performance of PcP PCR, the added benefits of PCR testing, future aspects/considerations, and how PCR may be best used in clinical algorithms to provide a probability of PcP.

Expert opinion: Given the current imperfect reference test for PcP, an alternative would be beneficial. Concerns over PcP PCR generating false positive results are valid but can be resolved by using positivity thresholds that drive specificity. Unfortunately, the extensive range of PCR assays complicates the provision of a PCR reference method. Combination testing incorporating PCR and B-D-Glucan, along with clinical and host risk factors, is key to understanding the individual probability of PcP. It is critical that access to PcP PCR testing is improved through technical and logistical development. Conversely, syndromic approaches including PcP need to be fully evaluated.

Introduction: Parkinson's disease (PD) is a complex disorder with vast clinical heterogeneity. Recent genetic, imaging and clinical evidence suggest that there are multiple subtypes of PD, and perhaps even distinct clinical entities, which are being diagnosed under the umbrella of PD. These might have similar clinical presentation, but potentially different underlying mechanisms, which, in future, will require different treatments. Despite extensive genetic research progress, genetic testing is still not a common practice in clinical patient care.

Areas covered: This review examines the numerous genes that have been discovered to affect the risk of, or cause, PD. We also outline genetic variants that affect PD age at onset, its progression, and the presence or severity of motor and non-motor symptoms. We differentiate between PD, other synucleinopathies, and atypical parkinsonism syndromes, and describe genes responsible for familial forms of typical PD and atypical parkinsonism. Lastly, we present current clinical trails that are underway for targeted therapies, particularly for GBA1-PD and LRRK2-PD which are the most significant subtypes.

Expert opinion: While genetic studies alone cannot be diagnostic for PD, proper utilization of genetic screening for PD could improve diagnostic accuracy and predictions for prognosis, guide treatment, and identify individuals that qualify for clinical trials.

Introduction: There have been many recent advancements in the treatment of bladder cancer including the approval of novel intravesical agents for non-muscle-invasive disease and systemic-targeted therapeutics for muscle-invasive and advanced disease. However, treatment strategies for bladder cancer are still largely based on clinicopathologic characteristics.

Areas covered: Based on primary literature sourced from PubMed, Embase, and Cochrane Library, we review the current status of molecular markers and biomarker panels with respective to their value in predicting response to standard chemotherapeutics and novel agents in non-muscle-invasive, muscle-invasive, and advanced bladder cancer.

Expert opinion: Several biomarkers based on molecular characterization of tumors and quantification of circulating tumor DNA have been associated with response or resistance to standard chemotherapeutics. More recent investigations have reported on predictive biomarkers for novel therapeutics in bladder cancer, although large-scale validation is still needed. Given the increasing therapeutic options for this disease, employment of such predictive biomarkers may help guide treatment selection and sequencing.

Background: This study investigated the relationship between lipid-associated loci identified through genome-wide association studies (GWAS) and the risk of peripheral artery disease (PAD), its severity, as well as clinical and laboratory features.

Research design and methods: A study included 1263 unrelated Russian subjects, consisting of 620 patients diagnosed with PAD and 643 healthy controls. Thirteen single nucleotide polymorphisms (SNP) were genotyped using the MassArray-4 system.

Results: Polymorphisms rs1689800, rs55730499 and rs881844 were found to be associated with an increased risk of PAD, whereas SNPs rs1883025, rs3136441, rs3764261 and rs6065906 showed protective effects against disease (P_perm ≤ 0.05). SNPs rs1689800, rs217406, rs1883025, and rs3136441 exhibited combined effects with cigarette smoking on the PAD risk (P_perm ≤ 0.05). Polymorphisms rs55730499 (beta = 0.124, P_perm = 0.04), rs9987289 (beta = 0.558, P_perm = 0.03), and rs881844 beta = -0.171, P_perm = 0.03) correlated with the ankle-brachial index. Multiple associations have been found between the SNPs and clinically significant characteristics, including disease severity, risk of gangrene, early disease onset, plasma procoagulant and atherogenic lipid changes (P_perm ≤ 0.05).

Conclusions: We identified novel genetic markers associated with PAD susceptibility and disease-related clinical and laboratory features. The identified biomarkers enhance the potential for predictive genetic testing related to the risk and progression of PAD, facilitating the integration of molecular diagnostics into clinical decision-making processes.

Introduction: Nonalcoholic fatty liver disease (NAFLD) is a common metabolism-related disease worldwide. Although studies have shown that some medications may be effective for treating NAFLD, they do not satisfy the medical requirements, and lifestyle changes are the most basic strategy. Thus, early detection of NAFLD and timely lifestyle interventions are highly important.

Areas covered: The traditional diagnostic methods for NAFLD are limited by accuracy, cost, and security issues. Cytokeratin 18 (CK18), which is a marker of apoptosis and overall cell death, is an excellent biomarker for NAFLD. Liver fat accumulation in NAFLD triggers the activation of caspases, which increases the CK18 cleavage and its release into the blood. CK18 can help diagnose different stages of NAFLD, especially the nonalcoholic steatohepatitis (NASH) stage. In evaluating the efficacy of the NAFLD treatment and predicting the risk of NAFLD-related diseases, CK18 plays a significant role.

Expert opinion: CK18 can non-invasively monitor the pathological conditions of NAFLD patients and provide new hope for the early diagnosis of NAFLD. Adding CK18 to the NAFLD diagnostic criteria that are widely used in clinical settings may be efficient for the detection of NAFLD and early effective intervention.

Introduction: Non-coding RNAs (ncRNAs) comprise a heterogeneous cluster of RNA molecules. Emerging evidence suggests their involvement in various aspects of tumorigenesis, particularly in gynecological malignancies. Notably, ncRNAs have been implicated as mediators within tumor signaling pathways, exerting their influence through interactions with RNA or proteins. These findings further highlight the hypothesis that ncRNAs constitute therapeutic targets and point out their clinical potential as stratification biomarkers.

Areas covered: The review outlines the use of small ncRNAs, including miRNAs, tRNA-derived small RNAs, PIWI-interacting RNAs and circular RNAs, for diagnostic, prognostic, and predictive purposes in gynecological cancers. It aims to increase our knowledge of their functions in tumor biology and their translation into clinical practice.

Expert opinion: By leveraging interdisciplinary collaborations, scientists can decipher the riddle of small ncRNA biomarkers as diagnostic, prognostic and predictive biomarkers of gynecological tumors. Integrating small ncRNA-based assays into clinical practice will allow clinicians to provide cure plans for each patient, reducing the likelihood of adverse responses. Nevertheless, addressing challenges such as standardizing experimental methodologies and refining diagnostic assays is imperative for advancing small ncRNA research in gynecological cancer.

Introduction: Approximately 15 million deaths occur globally each year due to infectious diseases. Timely diagnosis is crucial in promoting cure and preventing disease transmission. Currently, molecular diagnostics have replaced many conventional diagnostic tools due to their inherent limitations. However, the full potential of Immuno Polymerase Chain Reaction (IPCR) remains largely untapped.

Areas covered: This review focuses on the use of IPCR in the diagnosis of different bacterial diseases, highlighting its advantages over traditional methods.

Expert opinion: Early and accurate diagnosis of infectious diseases is crucial because it enhances treatment effectiveness, reduces morbidity and mortality, helps identify potential causes of sepsis earlier, and reduces the risk of unknowingly spreading the disease to others. IPCR in turn has shown promise for the early diagnosis of bacterial diseases as an alternative to conventional culture-based or serological diagnostic assays leading to delayed diagnosis and treatment. IPCR has the potential to revolutionize the diagnostic field due to its increased sensitivity and specificity. Although efforts are needed to reduce the time of the assay and to reduce background noise, IPCR can be combined with other platforms like lateral flow assay/biosensors/automation to improve its use as a point-of-care assay, especially in resource-limited settings.

Introduction: SARS-CoV-2, seasonal influenza, and respiratory syncytial virus (RSV) are major causes of acute respiratory infections in all age groups and responsible for an enormous socio-economic burden. The recently coined term 'tripledemic' describes co-circulation of these three viruses, a novel epidemiological paradigm that poses profound public health implications.

Areas covered: Real-time reverse transcription polymerase chain reaction (RT-PCR) is now considered the reference method for the diagnosis of SARS-CoV-2, influenza, and RSV infections. Syndromic-based multiplex RT-PCR panels that simultaneously detect several respiratory viruses have become increasingly common. This review explores available molecular diagnostics (MDx) platforms for the diagnosis of SARS-CoV-2, influenza, and RSV in the same biological sample. Within some limitations of the published validation and diagnostic accuracy studies, both laboratory-based and point-of-care multiplex panels proved highly performant in identifying SARS-CoV-2, influenza A, influenza B, and RSV. Improved operational efficiency and faster turnaround times make these assays potentially cost-effective or even cost-saving.

Expert opinion: The adoption of multiplex MDx assays for the contemporary detection of SARS-CoV-2, influenza, RSV, and other respiratory pathogens will likely increase in the next few years. To maximize the clinical usefulness and cost-effectiveness of these assays, locally issued guidelines and protocols on their implementation should be adopted.

Introduction: Liquid biopsy is an innovative advancement in oncology, offering a noninvasive method for early cancer detection and monitoring by analyzing circulating tumor cells, DNA, RNA, and other biomarkers in bodily fluids. This technique has the potential to revolutionize precision oncology by providing real-time analysis of tumor dynamics, enabling early detection, monitoring treatment responses, and tailoring personalized therapies based on the molecular profiles of individual patients.

Areas covered: In this review, the authors discuss current methodologies, technological challenges, and clinical applications of liquid biopsy. This includes advancements in detecting minimal residual disease, tracking tumor evolution, and combining liquid biopsy with other diagnostic modalities for precision oncology. Key areas explored are the sensitivity, specificity, and integration of multi-omics, AI, ML, and LLM technologies.

Expert opinion: Liquid biopsy holds great potential to revolutionize cancer care through early detection and personalized treatment strategies. However, its success depends on overcoming technological and clinical hurdles, such as ensuring high sensitivity and specificity, interpreting results amidst tumor heterogeneity, and making tests accessible and affordable. Continued innovation and collaboration are crucial to fully realize the potential of liquid biopsy in improving early cancer detection, treatment, and monitoring.