Unclassified green dots on nucleated red blood cells (nRBC) plot in DxH900 from a patient with hyperviscosity syndrome.

OBJECTIVES: Analytical interferences, caused by antibodies, often go unnoticed and require a deep understanding of analyzer principles in the correct clinical context. METHODS: A case report details a 56-year-old man with symptoms of hyperviscosity syndrome (HVS) due to multiple myeloma. RESULTS: The DxH 900 analyzer revealed abnormalities in the nucleated red blood cell (nRBC) graph, attributed to a high concentration of IgA kappa. Immediate plasmapheresis successfully treated HVS, reducing the monoclonal component and eliminating the aberrant green signal. CONCLUSIONS: In the appropriate clinical context, the recognition of analytical interferences is necessary for accurate clinical interpretation, and it is only possible with knowledge of the analytical principles of the instruments. In this case, the high concentration of IgA kappa generated an aberrant green signal in the VCSm.

Exploring the Nutritional and Bioactive Potential of Olive Leaf Residues: A Focus on Minerals and Polyphenols in the Context of Spain's Olive Oil Production.

Lyophilized plant-origin extracts are rich in highly potent antioxidant polyphenols. In order to incorporate them into food products, it is necessary to protect these phytochemicals from atmospheric factors such as heat, light, moisture, or pH, and to enhance their bioavailability due to their low solubility. To address these challenges, recent studies have focused on the development of encapsulation techniques for antioxidant compounds within polymeric structures. In this study, lyophilized olive leaf extracts were microencapsulated with the aim of overcoming the aforementioned challenges. The method used for the preparation of the studied microparticles involves external ionic gelation carried out within a water-oil (W/O) emulsion at room temperature. HPLC analysis demonstrates a high content of polyphenols, with 90% of the bioactive compounds encapsulated. Meanwhile, quantification by inductively coupled plasma optical emission spectroscopy (ICP-OES) reveals that the dried leaves, lyophilized extract, and microencapsulated form contain satisfactory levels of macro- and micro-minerals (calcium, potassium, sodium). The microencapsulation technique could be a novel strategy to harness the polyphenols and minerals of olive leaves, thus enriching food products and leveraging the antioxidant properties of the polyphenolic compounds found in the lyophilized extract.

Hidatidosis mesentérica y hepática en la costa caribe colombiana. Reporte de caso / Mesenteric and hepatic hydatid disease on the Colombian Caribbean coast. Case report

Introducción. La hidatidosis o equinococosis es una zoonosis parasitaria que se adquiere al ingerir huevos de cestodos del género Echinococcus. El diagnóstico clínico raramente se hace en sitios no endémicos. La mayoría de los pacientes se encuentran asintomáticos y los hallazgos incidentales en los estudios de imágenes o en procedimientos quirúrgicos permiten la sospecha diagnóstica. Caso clínico. Paciente masculino de 70 años, residente en área rural del municipio de Puerto Libertador, departamento de Córdoba, Colombia, quien consultó por masa abdominal en epigastrio y mesogastrio, parcialmente móvil e indolora. Resultados. En cirugía se identificaron lesiones quísticas mesentérica y hepática. Después de la cirugía y mediante estudios de inmunohistoquímica, se confirmó el diagnóstico de quiste hidatídico. El paciente tuvo una evolución satisfactoria. Conclusión. La hidatidosis quística mesentérica y hepática sintomática es una enfermedad rara en sitios no endémicos, donde la cirugía constituye un pilar fundamental en el diagnóstico y tratamiento, sumado al manejo médico farmacológico.

Introduction. Hydatidosis or echinococcosis is a parasitic zoonosis that is acquired by ingesting eggs of cestodes of the genus Echinococcus. Clinical diagnosis is rarely made in non-endemic sites. Most patients are asymptomatic and incidental findings on imaging studies or surgical procedures allow for diagnostic suspicion. Clinical case. A 70-year-old male patient, resident in a rural area of the municipality of Puerto Libertador, department of Córdoba, Colombia, who consulted for an abdominal mass in the epigastrium and mesogastrium, partially mobile and painless. Results. In surgery, mesenteric and hepatic cystic lesions were identified. After surgery and through immunohistochemistry studies, the diagnosis of hydatid cyst was confirmed. The patient had a satisfactory evolution. Conclusion. Symptomatic mesenteric and hepatic cystic hydatidosis is a rare disease in non-endemic sites, where surgery constitutes a fundamental pillar in the diagnosis and treatment in addition to pharmacological medical management.

Larvicidal Activity against Spodoptera frugiperda of some Constituents from two Diospyros Species. In silico Pesticide-likeness Properties, Acetylcholinesterase Activity and Molecular Docking.

This report informs for the first time the chemical constituents of Diospyros xolocotzii and Diospyros digyna, the pesticidal and the acetylcholinesterase (AChE) inhibition potential of some compounds calculated by in silico approaches, the larvicidal activity against Spodoptera frugiperda of available compounds, the AChE inhibition of selected compounds, and the results of the molecular docking of the most active ones with this receptor. From the aerial parts of D. xolocotzii were isolated pentacyclic triterpenes (1-4, 6, 10, 11-13), phytosterols (15-17), and isodiospyrin (18), whereas the analysis of aerial parts of D. digyna conducted to the isolation of pentacyclic triterpenes (4, 5, 7-9, 11-14), (4S)-shinanolone (19), and scopoletin (20). For comparison purposes, origanal (21) was chemically prepared from 11. The in silico analysis showed that the tested compounds have pesticide potential. The larvicidal activities of 11>13>12 indicated that the increase of the oxidation degree at C-28 increases their bioactivity. Compounds 11 and 21 presented the higher inhibition in the acetylcholinesterase assay, and the higher binding energies, and for the interactionswith AChE by molecular docking. Both Diospyros species are sources of triterpenes with pesticidal potential and the molecular changes in lupane triterpenes correlate with the observed bioactivity and molecular docking.

Olive Oil Waste as a Source of Functional Food Ingredients: Assessing Polyphenolic Content and Antioxidant Activity in Olive Leaves.

Around two million tons of olive oil are produced in Europe annually, with Portugal being among the top five European olive oil-producing countries. Olive oil production results in a substantial amount of waste in the form of olive leaves. These discarded olive leaves contain valuable phenolic compounds with antioxidant, anti-inflammatory, hypoglycaemic, neuroprotective, and antiproliferative properties. Due to their richness in polyphenols with health-promoting properties, olive leaves can be considered a potential functional food ingredient. Thus, sustainable practices for reusing olive leaf waste are in demand. In this study, the polyphenolic content in olive leaves from different Portuguese locations was determined using HPLC-UV-Vis after defining the best fit-for-purpose liquid extraction strategy. The differences in the in vitro antioxidant activity in these samples were determined by several methodologies based on radical scavenging (against 2,2'-azino-bis-3-ethylbenzthiazoline-6-sulphonic acid (ABTS), 2,2-diphenyl-2-picrylhydrazyl (DPPH), and peroxyl radical (ORAC)) and on reducing properties (cupric-reducing antioxidant capacity (CUPRAC), and Folin-Ciocalteu assay (FC)), to unveil the relationship between the profile and quantity of polyphenols with antioxidant mechanisms and their capacity. At last, the stability of extracted compounds upon lyophilization and exposition to surrogate biological fluids was assessed, envisioning the future incorporation of olive leaves extracted compounds in food products.

Differential expression and evolutionary diversification of RNA helicases in Boechera sexual and apomictic reproduction.

In higher plants, sexual reproduction is characterized by meiosis of the first cells of the germlines, and double fertilization of the egg and central cell after gametogenesis. In contrast, in apomicts of the genus Boechera, meiosis is omitted or altered and only the central cell requires fertilization, while the embryo forms parthenogenetically from the egg cell. To deepen the understanding of the transcriptional basis underlying these differences, we applied RNA-seq to compare expression in reproductive tissues of different Boechera accessions. This confirmed previous evidence of an enrichment of RNA helicases in plant germlines. Furthermore, few RNA helicases were differentially expressed in female reproductive ovule tissues harboring mature gametophytes from apomictic and sexual accessions. For some of these genes, we further found evidence for a complex recent evolutionary history. This included a homolog of Arabidopsis thaliana FASCIATED STEM4 (FAS4). In contrast to AtFAS4, which is a single-copy gene, FAS4 is represented by three homologs in Boechera, suggesting a potential for subfunctionalization to modulate reproductive development. To gain first insights into functional roles of FAS4, we studied Arabidopsis lines carrying mutant alleles. This identified the crucial importance of AtFAS4 for reproduction, as we observed developmental defects and arrest during male and female gametogenesis.

Predictors of unsustained measurable residual disease negativity in transplant-eligible patients with multiple myeloma.

ABSTRACT: The role of measurable residual disease (MRD) negativity as a biomarker to stop treatment is being investigated in transplant-eligible patients with multiple myeloma (MM). Thus, it is important to identify risk factors of MRD resurgence and/or progressive disease (PD) among patients achieving undetectable MRD to avoid undertreating them. Here, we studied 267 newly diagnosed transplant-eligible patients with MM enrolled in the GEM2012MENOS65 and GEM2014MAIN clinical trials who achieved MRD negativity by next-generation flow cytometry. After a median follow-up of 73 months since the first MRD negative assessment, 111 of the 267 (42%) patients showed MRD resurgence and/or PD. The only prognostic factors at diagnosis that predicted MRD resurgence and/or PD were an International Staging System (ISS) 3 and the presence of ≥0.01% circulating tumor cells (CTCs). Failure to achieve MRD negativity after induction also predicted higher risk of MRD resurgence and/or PD. Patients having 0 vs 1 vs ≥2 risk factors (ISS 3, ≥0.01% CTCs, and late MRD negativity) showed 5-year rates of MRD resurgence and/or PD of 16%, 33%, and 57%, respectively (P < .001). Thus, these easily measurable risk factors could help refine the selection of patients for whom treatment cessation after MRD negativity is being investigated in clinical trials. This trial was registered at www.clinicaltrials.gov as NCT01916252 and NCT02406144.

Poisoning by Baccharis coridifolia in Early-Weaned Beef Calves: Pathological Study and New Macrocyclic Trichothecene Identification.

This study investigated two outbreaks of spontaneous poisoning by Baccharis coridifolia (Asteraceae) in early-weaned beef calves in Tacuarembó, Uruguay. A total of 34 affected calves showed signs of salivation, anorexia, apathy, marked dehydration, and diarrhea. Deaths occurred 36-72 h after consumption and mortality varied from 37.5% to 43.3% for outbreak 1 and outbreak 2, respectively. The main pathological findings include diffuse severe necrosis of the prestomachs and lymphoid tissues. Ultrastructurally, epithelial cells of the rumen showed swelling, lysis of the organelles, degradation of intercellular attachments, and degradation of the nuclear chromatin. Using LC-MS with diagnostic fragmentation filtering, 56 macrocyclic trichothecenes including glycosyl and malonyl conjugates were identified. The total concentration of macrocyclic trichothecenes, including conjugates, was estimated to be 1.2 ± 0.1 mg/g plant material. This is the first report of these malonyl-glucose conjugates from Baccharis coridifolia.

Protein Plasma Levels of the IGF Signalling System Are Altered in Major Depressive Disorder.

The Insulin-like growth factor 2 (IGF-2) has been recently proven to alleviate depressive-like behaviors in both rats and mice models. However, its potential role as a peripheral biomarker has not been evaluated in depression. To do this, we measured plasma IGF-2 and other members of the IGF family such as Binding Proteins (IGFBP-1, IGFBP-3, IGFBP-5 and IGFBP-7) in a depressed group of patients (n = 51) and in a healthy control group (n = 48). In some of these patients (n = 15), we measured these proteins after a period (19 ± 6 days) of treatment with antidepressants. The Hamilton Depressive Rating Scale (HDRS) and the Self-Assessment Anhedonia Scale (SAAS) were used to measure depression severity and anhedonia, respectively. The general cognition state was assessed by the Mini-Mental State Examination (MMSE) test and memory with the Free and Cued Selective Reminding Test (FCSRT). The levels of both IGF-2 and IGFBP-7 were found to be significantly increased in the depressed group; however, only IGF-2 remained significantly elevated after correction by age and sex. On the other hand, the levels of IGF-2, IGFBP-3 and IGFBP-5 were significantly decreased after treatment, whereas only IGFBP-7 was significantly increased. Therefore, peripheral changes in the IGF family and their response to antidepressants might represent alterations at the brain level in depression.

Effect of a personalized nutritional intervention program on nutritional status, quality of life and mortality in hemodialysis patients.

Introduction: Objective: dietary advice provided through a nutritional intervention program (NIP) is recommended by renal clinic guidelines to prevent or treat malnutrition, that could improve quality of life (QoL) and survival in hemodialysis (HD) patients. This study set out to evaluate the effect of a personalized NIP on the nutritional status and its impact on QoL and mortality in dialyzed patients. Material and methods: this was a 12-month intervention study with regular follow-up in which nutritional parameters were measured at baseline and after 6 and 12 months. QoL was assessed by the Kidney Disease Quality of Life version 1.2 (KDQOL-SF) at baseline and at the end of the study. All dialyzed patients received individualized consultations with a trained dietitian. The content of the nutritional education program included a personalized meal plan and educational materials addressing nutrition to manage fluids, electrolytes, and vitamin D. Results: a total of 75 patients were included. After the NIP, visceral proteins, phosphorous, potassium and vitamin D levels had improved significantly (p < 0.001). The percentage of well-nourished patients increased by 30 % (p < 0.001). At the end of the study, the well-nourished patients had significantly improved scores on the general summary areas of the KDQOL-SF, reduced worry concerning fluid and dietary restrictions (p < 0.001), and the survival rate was 12 months longer (p < 0.01). Conclusion: the results of this study suggest that personalized NIP contributed to improved nutritional status, QoL and survival in HD patients.

Introducción: Objetivo: el asesoramiento dietético proporcionado a través de un programa de intervención nutricional (PIN) es recomendado por las guías clínicas renales para prevenir o tratar la desnutrición, puediendo mejorar la calidad de vida (CV) y la supervivencia en pacientes en hemodiálisis (HD). El objetivo de este estudio fue evaluar el efecto de un PNI personalizado sobre el estado nutricional y su impacto en la calidad de vida y la mortalidad en pacientes dializados. Material y métodos: estudio de intervención de 12 meses de duración, con seguimiento periódico de los pacientes en el que se midieron los parámetros nutricionales al inicio, a los 6 y 12 meses. La CV fue evaluada por el cuestionario Kidney Disease Quality of Life versión 1.2 (KDQOL-SF) al inicio y al final del estudio. Todos los pacientes dializados recibieron consultas individualizadas con un dietista. El contenido del programa de educación nutricional incluyó un plan de alimentación personalizado y materiales educativos sobre nutrición para el manejo de fluidos, electrolitos y vitamina D. Resultados: se incluyeron un total de 75 pacientes. Después del PIN, los niveles de proteínas viscerales, fósforo, potasio y vitamina D habían mejorado significativamente (p < 0,001). El porcentaje de pacientes bien nutridos aumentó un 30 % (p < 0,001). Al final del estudio, los pacientes bien nutridos mejoraron significativamente las puntuaciones en las áreas de resumen general del KDQOL-SF, redujeron la preocupación por las restricciones dietéticas y de líquidos (p < 0,001) y la tasa de supervivencia fue de 12 meses superior (p < 0,01). Conclusión: los resultados de este estudio sugieren que el PIN personalizado contribuyó a mejorar el estado nutricional, la calidad de vida y la supervivencia en pacientes en HD.

Levels of Bisphenol A and its analogs in nails, saliva, and urine of children: a case control study.

Introduction: A growing number of studies link the increase in overweight/obesity worldwide to exposure to certain environmental chemical pollutants that display obesogenic activity (obesogens). Since exposure to obesogens during the first stages of life has been shown to have a more intense and pronounced effect at lower doses, it is imperative to study their possible effects in childhood. The objective here was to study the association of Bisphenol A (BPA) and 11 BPA analogs in children, using three biological matrices (nails, saliva and urine), and overweight and obesity (n = 160). Methods: In this case-control study, 59 overweight/obese children and 101 controls were included. The measuring of Bisphenols in the matrices was carried out by ultra-high performance liquid chromatography coupled with triple quadrupole tandem mass spectrometry (UHPLC-MS/MS). Logistic regression was used to study the association between overweight/obesity and Bisphenol exposure. Results: The results suggested that BPF in nails is associated with overweight/ obesity in children (OR:4.87; p = 0.020). In saliva, however, the highest detected concentrations of BPAF presented an inverse association (OR: 0.06; p = 0.010) with overweight/obesity. No associations of statistical significance were detected between exposure to BPA or its other analogs and overweight/obesity in any of the biological matrices.

Evaluation of dietary arginine supplementation to increase placental nutrient transporters in aged mares.

Nine pregnant mares (18.2 ±â€…0.7 yr; 493.82 ±â€…12.74 kg body weight [BW]) were used to test the hypothesis that dietary supplementation of l-arginine would enhance placental vascularity and nutrient transport throughout gestation in aged mares. Mares were balanced by age, BW, and stallion pairing, and assigned randomly to dietary treatments of either supplemental l-arginine (50 mg/kg BW; n = 7) or l-alanine (100 mg/kg BW; n = 6; isonitrogenous control). Mares were individually fed concentrate top-dressed with the respective amino acid treatment plus ad libitum access to Coastal Bermudagrass hay. Treatments began on day 14 of gestation and were terminated at parturition. Mare BW, body condition score (BCS), and rump fat were determined, and body fat percentage was calculated every 28 d and concentrate adjusted accordingly. Doppler blood flow measurements including resistance index (RI) and pulsatility index for uterine artery ipsilateral to the pregnant uterine horn were obtained beginning on day 21 and continued every 7 d until day 154 of gestation, and prior to parturition. Parturition was attended with foaling variables and placental measures recorded. Placental tissue from the pregnant horn was analyzed histologically to assess cell-specific localization of vascular endothelial growth factor (VEGF) and cationic amino acid transporter 1 (SLC7A1) proteins. Semiquantitative analyses were performed using 10 nonoverlapping images per sample fixed in a 10× field (Fiji ImageJ v1.2). Mare performance data were analyzed using PROC MIXED in SAS and foaling and placental data were analyzed using PROC GLM. Gestation length at parturition was not influenced (P > 0.05) by supplemental arginine. Compared with arginine-supplemented mares, control mares had a thicker rump fat layer (P < 0.01) and greater percent body fat (P = 0.03), and BCS (P < 0.01) at parturition. Arginine-supplemented mares had a lower RI than control mares prior to parturition (P < 0.01). Body length, height, and BW of foals at birth, as well as placental weight and volume, and immunohistochemical staining for VEGF and SLC7A1 at parturition, were not affected (P > 0.05) by maternal arginine supplementation. These results indicate that dietary arginine supplementation (50 mg/kg BW) is safe for gestating mares. A larger number of mares is required to extend knowledge of effects of supplemental arginine on embryonic/fetal survival and growth in mares.

Evaluation of the Long-Lasting Flavour Perception after the Consumption of Wines Treated with Different Types of Oenological Additives Considering Individual 6-n-Propylthiouracil Taster Status.

Due to the limited scientific knowledge on the impact of commercial oenological additives on flavour perception, the aim of this work was to evaluate the effect of different types of oenological additives on the long-lasting flavour perception (flavour persistence) during wine tasting, also considering the effect of the individual PROP (6-n-propylthiouracil) taster status (PTS). To do so, white and red wines with two oenotannins (ellagitannin and gallotannin) and a commercial yeast mannoprotein were prepared. A control wine of each type was also made without additives. All the wines were spiked with a mixture of aromatic compounds responsible for the "fruity" and "woody" notes. Retronasal aroma and astringency were evaluated at the same time using time-intensity (TI) methodology and a trained panel (n = 40), including PROP non-tasters (NTs) and tasters (Ts). The results showed a significant effect of PTS on the long-lasting perception of astringency, being Ts who showed higher values than NTs for most TI parameters. However, PTS did not affect aroma persistence. In addition, the three oenological additives had an effect on astringency and retronasal aroma perception. They significantly increased the long-lasting perception of astringency compared to the control, while gallotannin also increased the persistence of the woody aroma.

Dasatinib-Induced Chylothorax: A Clinical Laboratory's Perspective.

Dasatinib is a tyrosine kinase inhibitor drug used for chronic myeloid leukaemia (CML) treatment. Chylothorax has been rarely reported as a secondary effect of dasatinib occurring especially in long-term treated patients, although its pathophysiology is not yet fully understood. Laboratory analysis of the pleural effusion is crucial for chylothorax diagnosis. We report a case of a 53-year-old male patient presenting a chylothorax after 14 years of dasatinib therapy where the clinical laboratory was key in the diagnosis.

Effect of THI on Milk Production, Percentage of Milking Cows, and Time Lying in Holstein Cows in Northern-Arid Mexico.

The possible effect of heat stress (HS), measured with the temperature-humidity index (THI) across seasons of the year (SY) upon milk production (MP), feed-to-milk efficiency (FME), and cow comfort (CC) was assessed in Holstein-Friesian cows in northern-arid Mexico. Data from 2467 cows (2146 milking and 321 dry) were recorded across SY [spring (SP), summer (SM), autumn (AT), and winter (WN)] between 2016 and 2019 in an intensive dairy farm located in the Comarca Lagunera (25° NL) with large fluctuations regarding ambient temperature and solar radiation. The THI was stratified into four classes: non-HS, <68; light HS, 68-71; moderate HS, 72-76; and intense HS, ≥77. The considered response variables were Milk production: both on a farm basis (totMP) and on a cow basis (cowMP); Nutritional efficiency: dry matter intake (DMI, kg); Feed conversion efficiency (FCE, kg) and energy-corrected milk (ECM, kg); Percentage of milking cows: (MC%); and Cow comfort: lying time (LT, h). Analyses of variance for unbalanced data were performed through "R". Both totMP and cowMP differed (p < 0.05) as HS increased; the largest values (i.e., 77,886 L and 35.9 L) occurred at lower THIs (i.e., <68 and 68-71) while the milk production fell (i.e., 66,584 L and 31.7 L) with the highest THIs (i.e., ≥77). Not only feed-to-milk efficiency (i.e., DMI, FCE, and ECM) but also the MC% exhibited a similar trend; a visible drop (p < 0.05) occurred from a THI of 68-71 onwards. Furthermore, the LT declined as the THI augmented, from 10.6 h at <68 to 8.5 h at ≥77. Moreover, differences (p < 0.05) also arose across seasons; TotMP, cowMP, DMI, FCE, and ECM revealed their largest (p < 0.05) values in WN and SP, halfway ones in AT, with the lowermost figures in SM. In the same way, cow comfort differed (p < 0.05) among seasons, with diverse lying times (h); WT, 10.5; AT, 10.20; SP, 9.3 h; and 8.8 in SM. Finally, the potential economic burden that HS caused at the producer (USD 233.2 million) and industry-market levels (USD 311.1 M), as well as its impact upon nutrient and alimentary security at the society level (i.e., 311 M milk liters and 195,415.82 Gcal), were also quantified.

Effects of infant feeding with goat milk formula or cow milk formula on atopic dermatitis: protocol of the randomised controlled Goat Infant Formula Feeding and Eczema (GIraFFE) trial.

INTRODUCTION: Atopic dermatitis (AD) is a chronic, inflammatory skin condition significantly affecting quality of life. A small randomised trial showed an approximately one-third lower incidence of AD in goat milk formula-fed compared with cow milk formula-fed infants. However, due to limited statistical power, AD incidence difference was not found to be significant. This study aims to explore a potential risk reduction of AD by feeding a formula based on whole goat milk (as a source of protein and fat) compared with a formula based on cow milk proteins and vegetable oils. METHODS AND ANALYSIS: This two-arm (1:1 allocation), parallel, randomised, double-blind, controlled nutritional trial shall enrol up to 2296 healthy term-born infants until 3 months of age, if parents choose to start formula feeding. Ten study centres in Spain and Poland are participating. Randomised infants receive investigational infant and follow-on formulas either based on whole goat milk or on cow milk until the age of 12 months. The goat milk formula has a whey:casein ratio of 20:80 and about 50% of the lipids are milk fat from whole goat milk, whereas the cow milk formula, used as control, has a whey:casein ratio of 60:40 and 100% of the lipids are from vegetable oils. The energy and nutrient levels in both goat and cow milk formulas are the same. The primary endpoint is the cumulative incidence of AD until the age of 12 months diagnosed by study personnel based on the UK Working Party Diagnostic Criteria. The secondary endpoints include reported AD diagnosis, measures of AD, blood and stool markers, child growth, sleep, nutrition and quality of life. Participating children are followed until the age of 5 years. ETHICS AND DISSEMINATION: Ethical approval was obtained from the ethical committees of all participating institutions. TRIAL REGISTRATION NUMBER: NCT04599946.

Cost-Effectiveness of Next-Generation Sequencing Versus Single-Gene Testing for the Molecular Diagnosis of Patients With Metastatic Non-Small-Cell Lung Cancer From the Perspective of Spanish Reference Centers.

PURPOSE: The aim of this study was to assess the cost-effectiveness of using next-generation sequencing (NGS) versus single-gene testing (SgT) for the detection of genetic molecular subtypes and oncogenic markers in patients with advanced non-small-cell lung cancer (NSCLC) in the setting of Spanish reference centers. METHODS: A joint model combining decision tree with partitioned survival models was developed. A two-round consensus panel was performed to describe clinical practice of Spanish reference centers, providing data on testing rate, prevalence of alterations, turnaround times, and treatment pathways. Treatment efficacy data and utility values were obtained from the literature. Only direct costs (euros, 2022), obtained from Spanish databases, were included. A lifetime horizon was considered, so a 3% discount rate for future costs and outcomes was considered. Both deterministic and probabilistic sensitivity analyses were performed to assess uncertainty. RESULTS: A target population of 9,734 patients with advanced NSCLC was estimated. If NGS was used instead of SgT, 1,873 more alterations would be detected and 82 more patients could potentially be enrolled in clinical trials. In the long term, using NGS would provide 1,188 additional quality-adjusted life-years (QALYs) in the target population compared with SgT. On the other hand, the incremental cost of NGS versus SgT in the target population was €21,048,580 euros for a lifetime horizon (€1,333,288 for diagnosis phase only). The obtained incremental cost-utility ratios were €25,895 per QALY gained, below the standard cost-effectiveness thresholds. CONCLUSION: Using NGS in Spanish reference centers for the molecular diagnosis of patients with metastatic NSCLC would be a cost-effective strategy over SgT.