Plasma C24:0- and C26:0-lysophosphatidylcholines are reliable biomarkers for the diagnosis of peroxisomal ß-oxidation disorders.

The gold-standard diagnostic test for peroxisomal disorders (PDs) is plasma concentration analysis of very long-chain fatty acids (VLCFAs). However, this method's time-consuming nature and limitations in cases which present normal VLCFA levels necessitates alternative approaches. The analysis of C26:0-lysophosphatydylcholine (C26:0-LPC) in dried blood spot samples by tandem-mass spectrometry (MS/MS) has successfully been implemented in certain newborn screening programs to diagnose X-linked adrenoleukodystrophy (ALD). However, the diagnostic potential of very long-chain LPCs concentrations in plasma remains poorly understood. This study sought to evaluate the diagnostic performance of C26:0-LPC and other very long-chain LPCs, comparing them to VLCFA analysis in plasma. The study, which included 330 individuals affected by a peroxisomal ß-oxidation deficiency and 407 control individuals, revealed that C26:0- and C24:0-LPC concentrations demonstrated the highest diagnostic accuracy (98.8% and 98.4%, respectively), outperforming VLCFA when C26:0/C22:0 and C24:0/C22:0 ratios were combined (98.1%). Combining C24:0- and C26:0-LPC gave the highest sensitivity (99.7%), with ALD females exhibiting notably higher sensitivity compared with the VLCFA ratio combination (98.7% vs. 93.5%, respectively). In contrast, C22:0-LPC exhibited suboptimal performance, primarily due to its low sensitivity (75%), but we identified a potential use to help distinguish between ALD and Zellweger spectrum disorders. In summary, MS/MS analysis of plasma C24:0- and C26:0-LPC concentrations represents a rapid and straightforward approach to diagnose PDs, demonstrating superior diagnostic accuracy, particularly in ALD females, compared with conventional VLCFA biomarkers. We strongly recommend integrating very-long chain LPC plasma analysis in the diagnostic evaluation of individuals suspected of having a PD.

Testing the stability of internal quality controls stored in the automated Atellica Solution refrigerated storage module.

Objectives: Atellica Solution (AS) is a platform that incorporates immunoassay and chemistry modules. AS is fitted with a refrigerated storage module (RSM) for internal quality controls (QC). The objective of this study was to assess the maximum permissible storage time in AS for QCs. Methods: A total of 48 analytes were tested using QC materials: Liquid Assayed Multiqual (MQ), Liquichek Immunology (LI), Liquichek Lipids (LL), and Liquichek Urine Chemistry (UC). The percentage of variation between results (Xt%) was calculated as the difference between the mean value of the triplicate performed at every time point of the study (Xt) and the average of the triplicate performed in the baseline time (Xo). Stability was assessed based on the total change limit (TCL), which combines analytical and biological variation: TCL=±âˆš((1.65 * CVa)2 + (0.5 * CVb)2). Results: A total of 40 of the 48 analytes tested remained stable at the end of the study. In relation to MQ and UC QCs, 32 of the 39 analytes remained stable for the whole study period (15 days) except for alkaline phosphatase, aspartate aminotransferase, calcium, lactate dehydrogenase, and total bilirubin in MQ, and chlorine and glucose in UC. In LI and LL QCs, eight of the nine analytes were stable throughout the 20 days of the study, except transferrin in LI. Conclusions: The Atellica Solution refrigerated storage module is a reliable system for the storage of quality control materials.

Evaluation of an immunoassay procedure to measure 6-monoacetylmorphine.

Introduction: 6-Monoacetylmorphine (6-MAM) is a specific metabolite of heroin. Thus, the presence of 6-MAM in urine is a definitive indication of heroin intake. The possibility of having an immunoassay procedure to measure 6-MAM would be a diagnosis tool to discriminate, among opiates-positive, those patients who have consumed heroin and those who have not.Methods: EMIT® II Plus 6-Acetylmorphine Assay was used to measure 6-MAM in urine. The positive opiate screening results were confirmed at the Toxicology laboratory of our hospital by GC-MS.Results: This study includes 63 urine samples from subjects admitted to emergency department with suspicion of opiate consumption. Specificity was evaluated in the two groups of samples studied. In the first group all samples which resulted negative by opiate immunoassay (n = 33) were negative for 6-MAM immunoassay test. Thus, the specificity obtained for 6-MAM immunoassay in this group was 100%. Regarding the second specificity study, performed in positive samples by opiate immunoassay which were negative to 6 MAM by GC-MS, the specificity decreased down to 75%. In the study of sensitivity all samples confirmed as positive to 6-MAM by confirmatory method (GC-MS) resulted positive by the screening method, thus sensitivity obtained was 100%.Discussion: In this study no FN for 6-MAM was observed and therefore the new Emit® II Plus 6- Acetylmorphine Assay procedure has a high NPV, thus a negative result with 6-MAM immunoassay practically excludes heroine consume. The positive results to 6-MAM by immunoassay should be confirmed by a more analytically specific method, such as GCMS.

Emerging biomarkers in the diagnosis of prostate cancer.

Prostate cancer (PCa) is the second most common cancer in men worldwide. A large proportion of PCa are latent, never destined to progress or affect the patients' life. It is of utmost importance to identify which PCa are destined to progress and which would benefit from an early radical treatment. Prostate-specific antigen (PSA) remains the most used test to detect PCa. Its limited specificity and an elevated rate of overdiagnosis are the main problems associated with PSA testing. New PCa biomarkers have been proposed to improve the accuracy of PSA in the management of early PCa. Commercially available biomarkers such as PCA3 score, Prostate Health Index (PHI), and the four-kallikrein panel are used with the purpose of reducing the number of unnecessary biopsies and providing information related to the aggressiveness of the tumor. The relationship with PCa aggressiveness seems to be confirmed by PHI and the four-kallikrein panel, but not by the PCA3 score. In this review, we also summarize new promising biomarkers, such as PSA glycoforms, TMPRSS2:ERG fusion gene, microRNAs, circulating tumor cells, androgen receptor variants, and PTEN gene. All these emerging biomarkers could change the management of early PCa, offering more accurate results than PSA. Nonetheless, large prospective studies comparing these new biomarkers among them are required to know their real value in PCa detection and prognosis.

The GALA study: relationship between galectin-3 serum levels and short- and long-term outcomes of patients with acute heart failure.

OBJECTIVE: We tested the hypothesis that early measurement of galectin-3 at the emergency department (ED) during an episode of acute heart failure (AHF) allows predicting short- and long-term outcomes. METHODS: We performed an exploratory study including 115 patients consecutively diagnosed with AHF in a single ED. Clinical and analytical variables were recorded. The primary endpoint was 30-day all-cause mortality, and secondary endpoints were 30-day composite outcome (death, rehospitalization or ED reconsultation, whichever first) and 1-year mortality. RESULTS: Seven patients (6.1%) died within 30 days and 43 (37.4%) within 1 year. The 30-day composite endpoint was observed in 21.1% of patients. Galectin-3 was correlated with NT-proBNP and the glomerular filtration rate but not with age and s-cTnI. Measured at time of ED arrival, galectin-3 showed good discriminatory capacity for 30-day mortality (AUC ROC: 0.732; 95% CI 0.512-0.953; p = 0.041) but not for 1-year mortality (0.521; 0.408-0.633; p = 0.722). Patients with galectin-3 concentrations >42 µg/L had an OR = 7.67(95%CI = 1.57-37.53; p = 0.012) for 30-day mortality. Conversely, NT-proBNP only showed predictive capacity for 1-year mortality (0.642; 0.537-0.748; p = 0.014). Patients with NT-proBNP concentrations >5400 ng/L had an OR = 4.34 (95%CI = 1.93-9.77; p < 0.001) for 1-year mortality. These increased short- (galectin-3) and long-term (NT-proBNP) risks remained significant after adjustment for age or renal function. s-cTnI failed in both short- and long term death prediction. No biomarker predicted the short-term composite endpoint. CONCLUSION: These results suggest that galectin-3 could help to monitor the risk of short-term mortality in unselected patients with AHF attended in the ED.