Clinical chemistry最新文献

Background: Hypertensive disorders of pregnancy (HDPs) complicate 8% to 9% of all pregnancies. They are a leading cause of maternal and neonatal morbidity and mortality and contribute to over $2.2 billion of health care expenditures annually. In 2023, the FDA first approved a soluble fms-like tyrosine kinase 1 to placental growth factor ratio system for HDP risk stratification; however, little is known about the implementation of such biomarker testing outside of research contexts.

Content: HDP severity drives clinical management and adverse perinatal outcomes. Placental biomarker testing aims to determine which patients are at risk for developing or progressing to the most severe HDPs. Widespread implementation of biomarker testing may increase access though it may not be cost-efficient or practice-changing for individual institutions. Accordingly, further attention must be paid to restrictive testing situations (e.g., low-resource settings) or even off-label uses (e.g., multiple gestations) that may solidify the role of biomarker testing in routine practice.

Summary: This review aims to outline clinical and institutional considerations for placental biomarker utilization in the context of their FDA-approved uses and to highlight the potential advantages and disadvantages of various testing strategies.

Background: Pregnancy induces a series of physiological adaptations, making accurate interpretation of clinical laboratory tests essential for maternal and fetal health. However, significant knowledge gaps persist in understanding how gestation affects circulating blood biochemistry, leading to potential clinical misinterpretations and underscoring the need for updated reference intervals in contemporary obstetric populations.

Methods: A cohort of approximately 135 healthy pregnant individuals was recruited with informed consent. Participants were excluded based on the use of prescribed medications, multiple gestations, age above 40 years, a history of chronic illness, or presence of acute illness during pregnancy. Blood samples were collected at 4 time points: 0 to 13 weeks, 14 to 27 weeks, 28 to 42 weeks, and 1 to 3 months postpartum. A total of 24 biochemical markers were analyzed. Statistically significant differences across gestational and early postpartum periods were assessed, and trimester-specific reference intervals were established.

Results: Of the 24 biochemical markers assessed, 17 exhibited statistically significant variations across gestation and the early postpartum period. Notably, albumin, total protein, creatinine, urea, uric acid, free thyroxine (FT4), and anemia markers showed significant decreases in late gestation compared to postpartum. Conversely, alkaline phosphatase, cholesterol, and triglycerides demonstrated substantial increases during gestation, followed by a marked decrease in the postpartum period.

Conclusion: This study provides comprehensive biochemical profiling of healthy pregnant individuals in Canada across gestation and the postpartum period. The findings highlight substantial alterations in circulating blood biochemistry during pregnancy, emphasizing the need for trimester-specific reference intervals to ensure accurate clinical test interpretation. Without such gestational age-specific benchmarks, maternal-fetal care standards remain suboptimal.

Background: Childhood cancers comprise a variety of liquid and solid tumors that display different patterns of incidence than adult cancers. Most have distinct molecular subtypes characterized by specific genomic driver events. The mutational processes that influence the somatic landscape of cancers also generate distinctive mutational signatures (mutSig). While these signatures are often inert, they do represent a fingerprint of the insult(s) present during mutagenesis. Associating mutSig with putatively causal exposures for pediatric cancer could inform future etiologic studies and elucidate the exposure pathways underlying risk.

Content: Here we review the epidemiology of pediatric cancers. We then summarize the knowledge around mutSig seen in pediatric cancer to date, discuss observed geographic and subtype-related variability, and discuss future efforts to characterize mutSig with unknown etiologies.

Summary: The diversity of childhood cancers and their molecular subtypes suggest etiologic heterogeneity. Detection of mutSig in childhood cancers has promoted hypothesis generation; e.g., the enrichment of UV-related signatures in aneuploid B-acute lymphoblastic leukemia has inspired new studies. Although the Mutographs projects were developed to investigate geographical variation in incidence, mutational epidemiology studies should also be employed to understand why certain mutSig are enriched in particular childhood cancers or subtypes. As pediatric cancers have lower mutational burdens than adult cancers, studying childhood cancer may also help determine the causes of mutSig with unknown etiologies. Given persistent differences in pediatric cancer risk by ancestry and socioeconomics, as well as the shifting global burden of childhood cancer, there is a need for studies with patients from diverse populations.

Background: Uterus transplantation (UTx) is uniquely positioned at the transition from experimental to clinical reality for women with absolute uterine factor insufficiency. As the technique gains wider clinical adoption, there is a growing need for standardization in both protocols and diagnostics.

Content: This review describes the current evaluation, monitoring, and emerging diagnostics in UTx across the main phases of care: (a) preoperative evaluation, which includes fertility evaluation and in vitro fertilization, surgical, psychosocial, and donor assessments, as well as donor-recipient matching considerations; (b) perioperative management, which focuses on acute surgical care, initiation of immunosuppression, and early graft evaluation; (c) posttransplant and pregnancy monitoring, which encompasses ongoing immunosuppression evaluation, biopsy interpretation, management of acute rejection, and detection and management of pregnancy and maternal complications; and (d) long-term follow-up, which addresses the potential for repeat pregnancies and planned graft hysterectomy to facilitate immunosuppression withdrawal.The review further explores future directions for clinical diagnostics in UTx, drawing on broader solid organ transplantation experiences. This includes molecular and allele-level human leukocyte antigen matching for recipient-donor compatibility, strategies for immunosuppression minimization, and the development of noninvasive rejection monitoring tools such as donor-derived cell-free DNA and novel blood and urine transcriptomics approaches.

Summary: Standardization of protocols and diagnostics is essential as UTx transitions to routine clinical practice. Emerging molecular diagnostics and noninvasive monitoring tools hold promise for improving graft outcomes and patient care in this evolving field.

Background: Hypertension, infection, hemorrhage, cardiovascular events, gestational diabetes, anemia, and miscarriage remain the primary cause of maternal mortality and morbidity. Despite advances in maternal health, there remains a gap in the ability to accurately diagnose, or predict the risk of, certain pregnancy-related conditions.

Content: Here, we discuss preterm delivery, preeclampsia, ectopic pregnancy, gestational diabetes, and detection of fetal anomalies. These are 5 examples of pregnancy-related conditions for which a significant diagnostic gap still exists. We note that many of the available tests used in this field promote a high negative predictive value (NPV), when tests with high positive predictive value (PPV) are needed to drive treatment.

Summary: To improve the modes of maternal testing, researchers need to establish the performance criteria necessary for the given condition. For low-prevalence conditions with potentially catastrophic outcomes, a single test needs extremely high sensitivity and specificity to achieve the PPV required to identify the small number of affected women who would benefit from intensive intervention. Alternatively, 2-step approaches could be used with a highly sensitive screen followed by a highly specific test. However, the solution to improving maternal morbidity and mortality is 2-fold: both affordable, effective, and rapid modes of testing; and safer, more effective treatments are needed.

Background: The field of pediatric cancer genetics has recently seen important advancements driven by collective international precision oncology trials and surveillance guideline development for childhood cancer predisposition syndromes (CPS). It is now recognized that 8%-18% of children with cancer will be identified with a pathogenic/likely pathogenic variant in a cancer predisposition gene. While progress has been significant, ongoing work is necessary to optimize the lifelong care of this growing population of individuals.

Content: This review provides an overview of the impact of 2 significant movements in the field of pediatric oncology: precision oncology trials utilizing paired tumor-germline sequencing and the development of expert-informed screening guidelines for the clinical care of children with childhood CPS. We summarize the influence these initiatives have had on patients and the clinical teams and institutions caring for them. We highlight current research that aims to elucidate the downstream effects of genetic testing and cancer surveillance for CPS to improve the efficacy of and access to CPS care as well as the psychosocial outcomes for patient and families living with a CPS. Finally, we discuss important areas of future research to better identify and care for this population across their lifespan.

Summary: A broadened or universal approach to testing for childhood CPS in pediatric oncology increases opportunities for early cancer detection and treatment for children and their family members. However, longitudinal studies on access to and the impact of this information and its consequences for families are needed for implementation into clinical practice.

Background: Preterm birth (PTB), or birth occurring before 37 weeks' gestation, remains a significant public health burden, accounting for 10% of live births annually in the United States and incurring substantial healthcare expenditures. Our understanding of the molecular mechanisms underlying spontaneous preterm birth (sPTB) has advanced across the previous 4 decades, yet precise prediction tools and prevention strategies are lacking.

Content: Numerous studies have identified potential anatomical and molecular risk factors for sPTB, including sonographic characteristics of the cervix; maternal serum circulating RNA and proteins; maternal urine metabolic byproducts; cervicovaginal cytokine, microbiome, and metabolome composition; amniotic fluid cytokines; umbilical cord blood leukocyte DNA methylation status; and placental transcriptome profiles. This review focuses on recent developments in sPTB biomarker determination among singleton gestations.

Summary: Herein, we synthesize and evaluate the test characteristics of candidate biomarkers of sPTB, concluding that no single biomarker can accurately predict sPTB. However, several individual or combined panels of biomolecules, including some commercially available, carry clinically significant predictive information. These biomarkers include cervical ultrasonography, the ratio of insulin-like growth factor-binding protein 4 to sex-hormone binding globulin, panels of urinary metabolites and amniotic fluid proteins, and maternal circulating cell-free RNA. Future integration of select biomarkers drawn from prospective validation cohorts into existing risk stratification strategies may enhance sPTB prediction, thereby identifying patients at greatest risk.

Background: Congenital heart defects (CHDs) are the most prevalent birth defects, contributing significantly to infant morbidity and mortality. While genetic factors account for a subset of CHDs, environmental exposures during critical periods of cardiac development are increasingly recognized as potential contributors.

Content: This review synthesizes current evidence linking per- and polyfluoroalkyl substances, polycyclic aromatic hydrocarbons, and other environmental contaminants to CHDs. We discuss epidemiological findings, biological mechanisms, exposure assessment methodologies, and future research directions, emphasizing the need for integrated approaches in understanding and mitigating environmental risks to fetal cardiac development.

Summary: This review emphasizes the need for integrated approaches in understanding and mitigating environmental risks to fetal cardiac development.