Healthcare contributes around 5-10% of global carbon emissions, alongside other pollutants, through utilization of over-stretched planetary resources. This creates a paradox in which efforts to protect health also genera...Healthcare contributes around 5-10% of global carbon emissions, alongside other pollutants, through utilization of over-stretched planetary resources. This creates a paradox in which efforts to protect health also generate risks to population health by contributing to the decline of planetary ecosystems- the foundation for health on which the healthcare system operates. This unsustainable cycle demands an urgent, unified front across all domains of clinical practice. Laboratory medicine, as a key entry point in the patient diagnostic pathway, is well-positioned to lead the required transformative change. While concepts such as sustainability and stewardship have been used interchangeably to rationalize resource use, the time has come to advance toward a model of 'degrowth' in the diagnostic laboratory. In healthcare, degrowth aims to minimize environmental harm by deliberately shrinking the consumption of unnecessary resources, particularly those from diagnostic and therapeutic interventions, without compromising patient outcomes. Diagnostic laboratories can support degrowth activities directly by adopting 'green laboratory' practices that include consuming less energy, minimizing waste (especially of reagents and non-recyclables) and optimizing test utilization by curbing low-value or unnecessary testing. They can also make an indirect impact by helping shift healthcare culture through shaping clinical guidelines using a degrowth lens, applying an environmental impact assessment whenever a new test is developed and advocating for sustainability declarations in publications that present new diagnostic approaches or technologies. When supported by effective stewardship programs, laboratories can serve as gatekeepers of diagnostic information and play a powerful role in aligning clinical decision-making with environmental responsibility. By embracing principles of degrowth in laboratory medicine, we have a chance, as well as a duty, to influence healthcare practices towards more ethical and environmentally responsible choices.
INTRODUCTION: A 4-year-old girl accidentally ingested an unknown quantity of bisoprolol (2.5 mg)-hydrochlorothiazide (6.25 mg) pills. Initialy asymptomatic, laboratory testing revealed elevated concentrations of cardiac...INTRODUCTION: A 4-year-old girl accidentally ingested an unknown quantity of bisoprolol (2.5 mg)-hydrochlorothiazide (6.25 mg) pills. Initialy asymptomatic, laboratory testing revealed elevated concentrations of cardiac and skeletal muscle injury markers. This case provided insight into potential myocardial toxicity and bone remodeling effects of these antihypertensive medications following acute overdose ingestion. MATERIALS AND METHODS: Upon admission, the patient underwent clinical and laboratory evaluations, which included electrocardiogram (ECG), echocardiography, blood gas analysis, and assessment of biochemical markers for cardiac injury (high sensitivity troponin [hs-TnI], N-terminal pro brain natriuretic peptide [NT-proBNP]) and bone turnover (parathyroid hormone [PTH], vitamin D, bone alkaline phosphatase [bALP], beta cross-laps [CTX]). Bisoprolol was measured in plasma and urine. Creatine kinase (CK) isoenzymes were performed on agarose gel electrophoresis. Activated charcoal was administered; fluids and electrolytes were closely monitored. Clinical and laboratory follow-up continued for two months. RESULTS: The child's vital signs were stable, but a reduced heart rate (75 bpm) developed within 24 h. Elevated hs-TnI and NT-proBNP levels indicated myocardial stress, despite normal ECG and echocardiography findings. The CK-BB isoenzyme increased to 8 % of total CK by day 3. An increase of CTX along with decreased PTH and bALP, suggested thiazide-induced osteoclastic activation. Bisoprolol concentrations quickly decreased over 12 h. The patient was discharged in good condition after 36 h. All biomarkers normalized progressively during follow-up. CONCLUSIONS: This case highlights subclinical myocardial toxicity and an unexpected bone remodeling after a pediatric overdose of bisoprolol-hydrochlorothiazide. CK-BB elevation, likely due to osteoclast activity, underscores the importance of monitoring skeletal biomarkers in thiazide exposures. Clinical recovery can occur before biochemical normalization, emphasizing the need for extended follow-up even in asymptomatic cases.
INTRODUCTION: Anti-GAD65 is an established diagnostic biomarker for autoimmune diabetes and neurological syndromes associated with GAD antibody-spectrum disorders. Automated chemiluminescence-based immunoassays such as M...INTRODUCTION: Anti-GAD65 is an established diagnostic biomarker for autoimmune diabetes and neurological syndromes associated with GAD antibody-spectrum disorders. Automated chemiluminescence-based immunoassays such as Maglumi are increasingly used, but their behavior at high antibody concentrations remains poorly characterized. We report the analytical concordance between Maglumi and radioimmunoassay (RIA), the cut-off titer that differentiates neurological from diabetic patients, and the hook effect of the immunoassay. MATERIALS AND METHODS: Anti-GAD65 levels were analyzed in samples from 90 patients with suspected autoimmune diabetes or neurological syndromes, using Maglumi 2000® and RIA (Medipan®). Analytical concordance was assessed by Passing-Bablok regression, Bland-Altman plots, and Cohen's kappa. ROC curve analysis identified diagnostic thresholds, and dilution studies were performed in samples with unexpectedly low values to assess a potential hook effect. RESULTS: Maglumi results were approximately five times higher than RIA results (slope = 5.364; R = 0.908); agreement was higher in endocrine (R = 0.998) than in neurological patients (R = 0.891). A cutoff of 6778 IU/mL discriminated neurological patients from diabetic patients (AUC = 0.96). Sixteen samples showed a hook effect, with direct (undiluted) values ≤273 IU/mL, while the corrected titers after dilution exceeded 20,000 IU/mL. A linear regression confirmed an inverse relationship between direct and true titers (r = -0.79, p < 0.05). DISCUSSION: Maglumi anti-GAD65 immunoassay provides reliable discrimination between endocrine and neurological patients but requires method-specific cutoffs to avoid misclassification. Hook effect was frequent in high-titer neurological samples, potentially leading to misdiagnosis, underscoring the need for routine dilution protocols to improve diagnostic reliability. CONCLUSIONS: Standardized dilution protocols and appropriate cutoffs are essential to ensure reliable anti-GAD65 testing with Maglumi chemiluminescent immunoassay, particularly in neurological indications.
INTRODUCTION: Helicobacter pylori (H. pylori) colonization increases the risk of upper gastrointestinal disorders and can be detected by various tests, including the stool antigen test (HpSAT). DiaSorin recommends an HpS...INTRODUCTION: Helicobacter pylori (H. pylori) colonization increases the risk of upper gastrointestinal disorders and can be detected by various tests, including the stool antigen test (HpSAT). DiaSorin recommends an HpSAT equivocal/indeterminate zone of 0.90-<1.10, but high variability observed in our laboratory prompted clinical implementation of a broader zone (0.60-<1.80). This study aimed to define an optimal HpSAT indeterminate zone using molecular as reference and urea breath test (UBT) for confirmation. MATERIALS AND METHODS: HpSAT and stool molecular results were available from 379 patients, of which 52 had follow-up UBTs. HpSAT was analyzed by the LIAISON HpSAT assay (DiaSorin), UBT by isotope ratio mass spectrometry, and molecular testing by qPCR targeting H. pylori DNA. Logistic regression modeled HpSAT index values against PCR positivity to define an optimal indeterminate zone, supported by clinical performance and flagging rates analyses. RESULTS: Logistic regression determined an HpSAT index of 0.79 (95 % CI: 0.34-1.14) had 90 % probability of a negative PCR result, and 4.99 (4.09-6.63) had 90 % probability of a positive result, rounded to an indeterminate zone of 0.80-<5.00. Lower thresholds assessed all had ≤ 2 % false negatives, while upper thresholds exhibited decreased false positive rates (22 % to 6 %) as thresholds increased (1.10 to 5.00), with minimal improvement beyond 3.00 (9 %). A modified zone of 0.80-<3.00 offered high accuracy with 12.9 % indeterminate results (DiaSorin's threshold: 2.8 %; laboratory's current threshold: 13.1 %). CONCLUSIONS: Our findings show that DiaSorin's HpSAT indeterminate zone is too narrow to reliably distinguish true positive and negative results in clinical practice. A modified broader zone (0.80-<3.00), derived via logistic regression using PCR as reference, improves diagnostic accuracy while minimizing indeterminate results.
OBJECTIVES: The use of point-of-care (POC) glucose meters and effectiveness of glycemic control should be monitored as part of quality assurance practices. This study is the first to establish indicators to evaluate the...OBJECTIVES: The use of point-of-care (POC) glucose meters and effectiveness of glycemic control should be monitored as part of quality assurance practices. This study is the first to establish indicators to evaluate the utilization of glucose meters in our academic hospital. METHODS: Patient results from glucose meters located in emergency department (ED), intensive care units (ICUs), general wards, and neonatal units were extracted from the data management system for the months of October to December from 2021 to 2023. Six indicators were developed and compared across clinical units, including: glucose test number per meter, daily frequency of patient glucose testing 1-4 times (%), ratio of POC to core lab glucose testing, and percentages of patient glucose results within target ranges, below critical level 2.5 mmol/L, or above 25.0 mmol/L. RESULTS: The six indicators varied greatly between clinical units due to the differences in patient populations, clinical scenarios, and clinical guidelines. About 90 % of patients in general wards, ED and neonatal units were tested glucose 1-4 times/day, while 27.1 % patients in ICUs were tested glucose 5-10 times/day or more. The average POC/core lab glucose testing ratio in neonatal units, general wards, ICUs, and ED was 17.6, 14.9, 2.2, and 0.3, respectively. Overall, 69.6 % of patient glucose results in all clinical units fell within the target ranges. Percentages of patient glucose results below 2.5 mmol/L or above 25.0 mmol/L were both under 0.6 % across clinical units. CONCLUSIONS: In this study, the indicators were able to assess the use of POC glucose meters and the effectiveness of glycemic control and to identify opportunities for quality improvement. The approach can be readily applied in other hospitals.
BACKGROUND: Iron deficiency (ID) and iron deficiency anemia (IDA) are prevalent and treatable conditions which disproportionately affect women. Serum ferritin is the most sensitive biomarker for ID and IDA, but its utili...BACKGROUND: Iron deficiency (ID) and iron deficiency anemia (IDA) are prevalent and treatable conditions which disproportionately affect women. Serum ferritin is the most sensitive biomarker for ID and IDA, but its utility in clinical decision making is limited by sex-specific reference intervals (RIs) that are frequently lower than evidence-based recommendations. The inclusion of asymptomatic, iron-depleted individuals in RI studies likely accounts for inappropriate ferritin thresholds, and a lower cutoff of 30 µg/L has been proposed by an expert consensus panel to improve sensitivity.In this study, we assessed ferritin RIs for diagnosing ID and IDA in our patient population. METHODS: Patient data, including age, sex assigned at birth, hemoglobin, and iron markers, were extracted from the laboratory information system (LIS). Patients were stratified into iron replete (IR), ID, or IDA groups based on measurements for iron, transferrin saturation, and hemoglobin. Ferritin values from the IR group were used to generate new reference ranges and receiver operator characteristic (ROC) curves were plotted to define optimal ferritin cutoffs for diagnosis of ID and IDA. RESULTS: Ferritin RIs generated from the IR group had lower limit cutoffs of 16.9 µg/L and 30 µg/L for females and males, respectively. Youden Index analysis of ROC curves identified optimal cutoffs of 45 µg/L and 70 µg/L for ID in females and males, respectively, improving diagnostic sensitivity by 44 % in the female group. CONCLUSIONS: These findings are consistent with recommendations for increasing ferritin cutoffs and demonstrate the need for clinical laboratories to re-examine ferritin RIs, particularly for ID diagnosis in the female patient population.
Dementia is the most common type of neurodegenerative disease, with Alzheimer's Disease (AD) constituting about two-thirds of these cases. In Canada, an estimated 674,000 individuals may have AD by 2031, nearly doubling...Dementia is the most common type of neurodegenerative disease, with Alzheimer's Disease (AD) constituting about two-thirds of these cases. In Canada, an estimated 674,000 individuals may have AD by 2031, nearly doubling from 2011. The total annual economic burden of dementia in Canada was about $40 billion in 2020, with an approximate average of $67,200 per person with dementia and if current trends continue, its annual burden could grow by 275 % over 30 years. AD is a double proteinopathy with its fundamental neuropathologic features defined by amyloid-beta (Aβ) plaques and neurofibrillary tangles with aggregated tau proteins. This supports the potential for mechanism-based proteomic biomarkers to be detected in biofluids. Pathophysiologic and topographical biomarkers have significantly improved the diagnosis of typical and atypical phenotypes of AD, helping clinicians recognize and differentiate AD phenotypes from other types of dementia and neurodegenerative diseases. The cerebrospinal fluid Aβ42/Aβ40 ratio measurement is a robust biomarker in detecting cerebral Aβ pathology and AD diagnosis. A number of very sensitive assays for measuring AD blood biomarkers including p-tau217, front-runner candidate for AD diagnosis, have been developed during last years. In this review we discuss the biological configuration and normal function of involved proteomics in AD including Aβ and tau protein, particularly tau phosphorylation and biochemistry of tau isoforms and their detection feasibility in plasma using novel technologies. Then, we critically review blood-based biomarkers' analytical and clinical validations, focusing more on plasma p-tau217 and their availability and prospects in Canada.
OBJECTIVES: Calculated, small dense low-density lipoprotein cholesterol (CsdLDL-C), derived using the Sampson equation, has been proposed as a screening tool for atherosclerotic cardiovascular disease risk. The current s...OBJECTIVES: Calculated, small dense low-density lipoprotein cholesterol (CsdLDL-C), derived using the Sampson equation, has been proposed as a screening tool for atherosclerotic cardiovascular disease risk. The current study investigated the utility of CsdLDL-C and calculated large buoyant low-density lipoprotein cholesterol (ClbLDL-C) for coronary artery disease (CAD) risk assessment in a Thai population. METHODS: This study included 6448 participants without prior CAD from the Electricity Generating Authority of Thailand (EGAT) prospective cohort (2007-2009). CsdLDL-C and ClbLDL-C were estimated from standard lipid panel measurements. Associations with CAD risk were evaluated using Kaplan-Meier survival analysis and Cox proportional hazards models. RESULTS: Over a mean follow-up period of 10.24 ± 1.01 years, 262 (4.06 %) participants experienced CAD events. At the optimal cutoffs, high CsdLDL-C [>1.08 mmol/L (41.85 mg/dL)] was significantly associated with incident CAD events (HR = 1.57; 95 % CI = 1.22-2.02), whereas high ClbLDL-C [>2.52 mmol/L (97.59 mg/dL)] was inversely associated with incident CAD events (HR = 0.72; 95 % CI = 0.56-0.92). The CsdLDL-C/ClbLDL-C ratio exhibited the strongest association (HR = 2.02; 95 % CI = 1.58-2.60) among all lipid parameters. When individually added to the pooled cohort risk equation, CsdLDL-C and the CsdLDL-C/ClbLDL-C ratio remained significant predictors of new-onset CAD. They also demonstrated good discriminatory power (P < 0.004). CONCLUSION: CsdLDL-C and ClbLDL-C, derived using the Sampson equation, were significantly associated with CAD risk in the opposite direction. Their ratio had greater predictive effectiveness. Incorporating CsdLDL-C and the CsdLDL-C/ClbLDL-C ratio into cardiovascular risk assessment models may improve early identification of at-risk individuals.
Modified low-density lipoproteins (LDL) play a pivotal role in the pathogenesis of atherosclerosis, contributing to plaque formation and vascular inflammation. This review explores how a diverse array of forms of modifie...Modified low-density lipoproteins (LDL) play a pivotal role in the pathogenesis of atherosclerosis, contributing to plaque formation and vascular inflammation. This review explores how a diverse array of forms of modified LDL, including carbamylated LDL, nitrated LDL, and desialylated LDL, along with various enzymatic modifications, contribute to disease progression. We discuss how these alterations promote the formation of a heterogeneous, highly atherogenic pool of particles known as electronegative LDL (LDL(-)). Mechanistic insights highlight pathways involving upregulated scavenger receptors, foam cell formation, and chronic inflammatory responses. The diagnostic and prognostic implications of LDL(-), including its association with autoimmune conditions like rheumatoid arthritis and chronic conditions such as type 2 diabetes, underscore its potential as a biomarker for cardiovascular risk. Emerging therapies targeting LDL(-), such as nanoformulations of single-chain fragment variable antibodies, demonstrate promising efficacy in reducing lesion size and inflammation without adverse systemic effects. Despite these advances, a critical barrier to clinical translation is the lack of standardised, high-throughput assays suitable for routine laboratory use. Future research must therefore prioritise the development and validation of robust clinical assays to quantify these atherogenic particles, a crucial step for establishing their role in advanced risk stratification and for guiding novel therapeutic strategies..
OBJECTIVES: Metabolic disorders in newborns can cause significant morbidity and mortality if not diagnosed and managed early. In this study, we developed and validated a reliable LC-MS/MS method to simultaneously quantif...OBJECTIVES: Metabolic disorders in newborns can cause significant morbidity and mortality if not diagnosed and managed early. In this study, we developed and validated a reliable LC-MS/MS method to simultaneously quantify methylmalonic acid, methylcitric acid, malonic acid, ethylmalonic acid, and total homocysteine associated with metabolic disorders. DESIGN AND METHODS: According to Clinical Laboratory Standards Institute (CLSI) guidelines, various analytical performances (i.e., precision, linearity, accuracy and reference intervals) were rigorously evaluated. Meanwhile, sample preparation, chromatographic separation and mass spectrometric detection and incorporating stable isotope-labeled internal standards were optimized. Furthermore, calibrators and quality controls were developed to ensure standardization and traceability. RESULTS: The coefficient of variations for precision were less than 10.0 %. Meanwhile, the results showed high accuracy (recoveries: 94.57 %-109.60 %) and robust linearity (R > 0.9935) over clinically relevant ranges. The limits of detection and limits of quantification for all analytes were established, enabling sensitive detection of pathological elevations. Reference intervals for pediatric populations (ages 0-1 month and 2 months to 18 years) were determined, providing essential baselines for clinical interpretation. CONCLUSIONS: The newly developed method demonstrated good analytical performance and offers a standardized, high-throughput solution for clinical laboratories to improve early diagnosis and personalized management of metabolic diseases.
INTRODUCTION: Cholesterol metabolism dysregulation is recognized as one of the hallmarks of the cancer with highest mortality rate and the second most common malignancy - lung cancer (LC). LDL and HDL particles, the latt...INTRODUCTION: Cholesterol metabolism dysregulation is recognized as one of the hallmarks of the cancer with highest mortality rate and the second most common malignancy - lung cancer (LC). LDL and HDL particles, the latter being carriers of the antioxidant paraoxonase-1 (PON1), were already proven to be altered in cancer patients. We have tried to investigate in more depth the cholesterol metabolism perturbances in LC, by analzying content of each of the LDL and HDL subclass and (anti)oxidative activity of each of the HDL subclass separately. MATERIALS AND METHODS: LDL and HDL subclasses from blood samples of 89 LC patients and 84 healthy subjects were separated and HDL subclasses PON1 activity assessed using Rainwater method and Gugliucci's zymogram method, respectively. RESULTS: LC patients had higher relative proportion of HDL 2 particles, lower proportion of HDL 3 particles, and significantly lower activity of PON1 compared to control group (CG). Relative proportion of PON1 activity was higher on HDL 2b fraction and lower on all HDL 3 fractions of LC patients compared to CG. Relative proportions of LDL I and LDL II particles were increased, while proportions of LDL IV and small dense LDL particles were decreased in LC patients. Relative proportions of HDL and LDL subfractions and PON1 activities on HDL subfractions were found to be dependent on LC type and size, number of comorbidities and sites of progression, and overall response to therapy. CONCLUSION: PON1 activity and lipoprotein subfractions distribution seem to be indicators of possible metabolic pathways (disorders) in LC.
BACKGROUND AND AIMS: Mucopolysaccharidosis (MPS) types I and II are two types of rare lysosomal storage diseases, which lead to the accumulation of glycosaminoglycans due to the lack of the enzyme alpha-L-iduronidase and...BACKGROUND AND AIMS: Mucopolysaccharidosis (MPS) types I and II are two types of rare lysosomal storage diseases, which lead to the accumulation of glycosaminoglycans due to the lack of the enzyme alpha-L-iduronidase and iduronate 2-sulfatase respectively. There are some similar pathogenic mechanisms and clinical phenotypes but also some specific minute manifestations between these two subtypes. MATERIALS AND METHODS: We used tandem mass tag mass spectrometry to analyze the differential protein profiles in the urine of MPS I and MPS II patients, and then used parallel reaction monitoring (PRM) to verify our results. We detected the differentially expressed proteins (DEPs) of MPS I and MPS II compared with the control group separately. RESULTS: We focused on 227 DEPs which showed consistent changes in the urine of both MPS I and MPS II. PRM analysis verified that up-regulated hexosaminidase B and down-regulated hemoglobin alpha-1 showed significant difference in the urine of both subtypes. In addition, we found 391 DEPs by comparative analysis of MPS I and MPS II proteomes and found that DHRS2 contributed to the difference between the two subtypes by PRM verification. CONCLUSION: We found that the urine of the two subtypes showed up-regulated HEXB and down regulated HBA1, while DHRS2 was significantly different in the urine of the two subtypes.
INTRODUCTION: Dihydropyrimidine dehydrogenase (DPD) is the enzyme implicated in the catabolism of the fluoropyrimidines (FP), a class of chemotherapeutics used to treat many cancers. The DPYD gene is known to have a huge...INTRODUCTION: Dihydropyrimidine dehydrogenase (DPD) is the enzyme implicated in the catabolism of the fluoropyrimidines (FP), a class of chemotherapeutics used to treat many cancers. The DPYD gene is known to have a huge number of variants potentially associated with DPD deficiency. Therefore, phenotypic and genotypic characterization of DPD is fundamental for cancer patients before undergoing treatment with FP. The AIOM (Italian Association of Medical Oncology) requires genetic analysis, with the purpose to identify a panel of 5 single nucleotide polymorphisms associated with 5-fluorouracil (5-FU)-induced toxicity, while the biochemical test, which measures uracil levels to predict the residual activity of DPD, is only recommended and not mandatory. METHODS: Single nucleotide polymorphisms were analyzed by real-time polymerase chain reaction (PCR) from peripheral blood. Uracil and dihydrouracil were quantified using an ultra-performance liquid chromatography/tandem mass spectrometry system in plasma obtained from patients before 5-FU treatment. Sanger sequencing was performed for the DPYD gene. RESULTS: Here, we describe the case of a 70-year-old Caucasian male patient with pancreatic cancer for whom real-time PCR highlighted a heterozygous pathogenic variant c.1905 + 1G > A associated with a 50 % reduction of DPD enzymatic activity. This finding was not confirmed by the biochemical test which revealed a complete absence of DPD activity. By performing Sanger sequencing, we highlighted the concomitant presence of a likely pathogenic variant c.2622 + 1G > A, not compatible with the administration of 5-FU. CONCLUSION: Thus far, guidelines provide a limited panel for the identification of pathogenic or likely pathogenic variants of the DPYD gene, therefore we encourage the mandatory use of biochemical tests as a precise diagnostic strategy to detect rare variants and improve drug administration.
OBJECTIVE: This present study aimed to measure platelet factor 4 (PF4) protein level in follicular fluid of patients with polycystic ovary syndrome (PCOS) and analyzed the correlation between follicular PF4 level with cl...OBJECTIVE: This present study aimed to measure platelet factor 4 (PF4) protein level in follicular fluid of patients with polycystic ovary syndrome (PCOS) and analyzed the correlation between follicular PF4 level with clinical characteristics. METHODS: Sixty-seven women (36 PCOS patients vs. 31 non-PCOS women) were enrolled in the study. Follicular fluid PF4 level was analyzed by enzyme-linked immunosorbent assay. RESULTS: The level of PF4 was significantly higher in follicular fluid of patients with PCOS than that of non-PCOS controls (50.5 (95 % CI: 42.8 to 115.86) ng/ml vs. 37.42 (95 % CI: 23.01 to 49.69) ng/ml, p < 0.001). Correlation analysis showed that the level of PF4 was positively related with serum anti-Mullerian hormone (r = 0.3809, p = 0.0015), serum testosterone (r = 0.3629, p = 0.0025), antral follicle count (r = 0.5544, p < 0.0001), and number of oocytes retrieved (r = 0.3799, p = 0.0018) in all patients. The area under the curve of PF4 level in follicular fluid to predict PCOS was 0.723 (95 % CI: 0.600 to 0.847). CONCLUSIONS: Our study demonstrated that the PF4 level was higher in the follicular fluid of patients with PCOS and was associated with key features of PCOS, suggesting that PF4 may play a role in the pathogenesis of PCOS.
BACKGROUND: 5-Fluorouracil (5-FU) and its pro-drug, capecitabine, are widely used to treat solid tumors. Patients with dihydropyrimidine dehydrogenase (DPYD) deficiency are at increased risk for severe treatment-related...BACKGROUND: 5-Fluorouracil (5-FU) and its pro-drug, capecitabine, are widely used to treat solid tumors. Patients with dihydropyrimidine dehydrogenase (DPYD) deficiency are at increased risk for severe treatment-related toxicity. This study reported the implementation of DPYD genotyping in clinical practice and assessed the impact of genotype-guided dosing on clinical outcomes. METHODS: An in-house pharmacogenomic testing using the Elucigene DPYD genotyping kit (Yourgene Health, UK) was established to detect the four most common clinically actionable DPYD alleles, including *2A, *13, HapB3 and c.2846A>T (rs67376798). Six months post-implementation, a retrospective chart review assessed genotype results, chemotherapy regimens, dose modifications, adverse events related to 5-FU or capecitabine, and demographics. Data were de-identified for analysis. RESULTS: Analytical validation of the DPYD assay showed 100 % sensitivity, specificity, accuracy, reproducibility, and repeatability. The genotyping workflow was successfully integrated into clinical practice, with a rapid turnaround time to meet oncology treatment planning. From July to December 2024, 299 patients underwent DPYD testing; variants were identified in 22 patients, including 20 patients (6.7 %) with clinically significant variants conferring a reduced DPD function and 2 patients with a variant (c.483 + 18G>A; rs56276561) that retains normal DPD function. Among those variants, HapB3 (n = 18) was the most frequent one, characterized by c.1129-5923C>G and c.1236G>A (rs75017182, rs56038477) co-occurring with c.483 + 18G>A (rs56276561). Of 233 patients receiving 5-FU-based chemotherapy, 13 were variant carriers. Genotype-guided dosing allowed early dose optimization, and all carriers completed at least three treatment cycles, with one severe adverse event attributed to oxaliplatin rather than 5-FU. CONCLUSIONS: This study reported the integration of DPYD pharmacogenomic testing into oncology care and evaluated the post-implementation clinical outcomes, highlighting the critical role of pharmacogenomic testing in optimizing cancer treatment and improving patient safety.