Introduction: This study established laboratory and trimester specific indirect reference intervals (RIs) for thyroid stimulating hormone (TSH). Materials and methods: A retrospective observational study was performed at a tertiary-care laboratory’s hospital during 12 months. Between February 2023 and February 2024, TSH results from 2166 women in their first trimester of pregnancy were retrieved. Only outpatients coming from primary care were included in the study. After applying exclusion and outlier criteria, TSH results from 1300 patients were analyzed to establish new RIs using the 2.5th and 97.5th percentiles by the non-parametric percentile method. These RIs were verified by an indirect method analyzing 486 TSH results from a cohort of pregnant women that were extracted from April to June 2024, and a direct prospective study of 28 pregnant women from a primary care center. All TSH tests were measured using a Cobas 8000 e801 system (Roche, Basel, Switzerland). Results: The TSH RIs were 0.60-4.33 mIU/L. Both verification methods met the requirements of the CLSI guidelines. Conclusions: The indirect method could be used to establish and verify local RIs for TSH in first trimester pregnant women. This may reduce misclassification of pregnant women undergoing thyroid function tests.

The need for prostate cancer (PCa)-specific biomarkers that enable more accurate detection of the disease and better prediction of tumor aggressiveness remains ongoing due to the low cancer specificity of PSA screening. Several potential mRNA markers for diagnosing PCa, in tissue and urine, have been reported in the literature. In this study, we aim to explore the potential of selected prostate-specific molecules and transcripts contained in small extracellular vesicles (sEVs) in semen to predict PCa risk reclassification for patients with moderately elevated PSA levels—a clinical scenario where identifying truly non-invasive biomarkers is especially critical. RT-qPCR analysis in semen sEVs successfully showed differential expression of KLK3 and PCA3 genes between PCa and healthy controls, whereas CREB3L4, CCNQ and DUSP23 levels were related to the severity or degree of PCa affectation. Our findings also present strong evidence that classifiers based on combined long transcript levels in semen sEVs serve as effective biomarkers. They can be used alone or in combination with blood PSA and/or semen citric acid levels to improve the diagnosis of PCa and assess its severity and disease progression with high accuracy. This strategy would allow a more comprehensive assessment, increase prognostic accuracy, and facilitate accurate clinical decision-making in the management of PCa.

Introduction: Defining trustworthy reference intervals (RIs) for serum folate (FOL) or serum cobalamin (VITB12) is a difficult task. The purpose of this study is to use an indirect approach from the laboratory information’s system to indirectly generate RIs for FOL and VITB12. Materials and methods: A retrospective observational study was performed at a tertiary-care laboratory’s hospital during 12 months. All FOL and VITB12 tests were measured using a Cobas8000 e801 system (Roche Diagnostics, Mannheim, Germany). The RIs were calculated using a non-parametric approach. The RIs established in the present study were verified by calculating the fraction of RIs that fell outside the new RIs, in two validation cohorts sampled using the direct and indirect method. Results: A total of 19,214 (FOL) and 27,420 (VITB12) results were obtained. The RIs were 4.5 nmol/L (90% confidence intervals (CI) 4.4-4.6) to 38.4 nmol/L (CI 38.3-38.5) for FOL and 140 pmol/L (CI 139-141) to 659 pmol/L (CI 657-660) for VITB12. The verification included 8,798 FOL results and 7,365 VITB12 results. For both magnitudes was acceptable since only 0.1% of FOL and 0.02% of VITB12 results fell outside the RIs. Finally, the RIs were verified using a direct method with twenty individuals. For FOL 20/20 cases and 19/20 of VITB12 cases fell within the estimated RIs. Conclusions: In summary, the use of an indirect data approach has enabled us to calculate RIs for FOL and VITB12. The RIs obtained in our study are lower than those proposed by the manufacturer for both FOL and VITB12.

Cancer cachexia is a frequent complication of patients diagnosed with non-small cell lung cancer (NSCLC) that affects their quality of life and their prognosis. A detailed, multidimensional characterization of patients with cancer cachexia is lacking. We conducted a prospective study of 52 patients diagnosed with locally advanced unresectable NSCLC who underwent concurrent chemoradiotherapy followed by immunotherapy. At baseline, 53% of patients met the Fearon’s criteria for cachexia. Cachexia was significantly associated with tumor stage (p < 0.001), performance status (p = 0.027), lower skeletal muscle index (p = 9e-4) and total adipose tissue index (p = 0.004), elevated C-Reactive Protein blood levels (p = 0.004), moderate to severe malnutrition (p < 0.001), reduced caloric intake (p = 0.007) and diminished physical strength (p = 0.001). Proteomic profiling using the O-link platform revealed known and novel biomarkers of cachexia, including inflammatory cytokines. Cachexia was significantly associated with elevated serum levels of CCL23, IL-6, CSF1, complement factor C1QA, motilin, agouti-related protein (AGRP) and soluble CD4 and CD276, and with lower RANKL, CKAP4, LRRN1, FLT3LG or Persephin, among others. These proteins showed varying degrees of correlation with caloric intake. GDF-15 was associated with weight loss (p = 0.00014), but not with cachexia (p=0.08), calorie intake or body composition. This prospective study demonstrates that cancer cachexia is highly prevalent in patients with unresectable locally advanced NSCLC and is associated with specific, understudied cytokines. These findings provide further insight into the biological characterization cachexia and may help identify novel targets for therapeutic interventions.