Increased incidence and mortality from Listeria monocytogenes infection in Spain.

BACKGROUND: Listeria monocytogenes (LM) is a health treat worldwide given its high mortality and the growing of high-risk susceptible populations. METHODS: All hospitalizations with a diagnosis of LM in the National Registry of Hospital Discharges were examined in Spain from 2000 to 2021. RESULTS: A total of 8,152 hospital admissions with LM were identified. The mean age was 59.5 years and 48% were immunosuppressed (IS). The rate of LM hospitalizations increased from 5 per 1 million population in 2000 to 8.9 in 2021 (p<0.001). A foodborne outbreak in Andalusia determined a sharp increase of admissions with LM during 2019. The COVID-19 pandemic and lockdowns were associated with a fall in LM admissions. The overall in-hospital mortality was 16.7%. The number of deaths in patients hospitalized with LM rose from 7.8 per 100,000 deceased in 2000 to 18 in 2021 (p<0.001). After adjustment, age >65 years-old (Odds ratio [OR]=2.16), sepsis (OR=2.60), meningoencephalitis (OR=1.72), endocarditis (OR=2.0), neonatal listeriosis (OR=2.10) and IS (OR=2.09) were associated with mortality. CONCLUSIONS: The number of patients hospitalized with LM in Spain has risen significantly from 2000 to 2021. The increase in the rate of admissions and deaths was largely driven by the growing proportion of elderly and of immunosuppressed patients.

Pancreatic cancer biomarkers: A pathway to advance in personalized treatment selection.

Pancreatic cancer is one of the tumors with the worst prognosis, and unlike other cancers, few advances have been made in recent years. The only curative option is surgery, but only 15-20% of patients are candidates, with a high risk of relapse. In advanced pancreatic cancer there are few first-line treatment options and no validated biomarkers for better treatment selection. The development of targeted therapies in pancreatic cancer is increasingly feasible due to tumor-agnostic treatments, such as PARP inhibitors in patients with BRCA1, BRCA2 or PALB2 alterations or immunotherapies in patients with high microsatellite instability/tumor mutational burden. In addition, other therapeutic molecules have been developed for patients with KRAS G12C mutation or fusions in NTRK or NRG1. Consequently, there has been a growing interest in biomarkers that may help guide targeted therapy in pancreatic cancer. Therefore, this review aims to offer an updated perspective on biomarkers with therapeutic potential in pancreatic cancer.

Improvement of thrombosis management in patients with cancer: a practical consensus document of recommendations for cancer-associated thrombosis patients' healthcare in Spain.

Cancer patients are at risk of venous thromboembolism (VTE), its recurrence, but also at risk of bleeding while anticoagulated. In addition, cancer therapies have been associated to increased VTE risk. Guidelines for VTE treatment in cancer patients recommend low molecular weight heparins (LMWH) or direct oral anticoagulants (DOAC) for the initial treatment, DOAC for VTE short-term treatment, and LMWH or DOAC for VTE long-term treatment. This consensus article arises from a collaboration between different Spanish experts on cancer-associated thrombosis. It aims to reach an agreement on a practical document of recommendations for action allowing the healthcare homogenization of cancer-associated thrombosis (CAT) patients in Spain considering not only what is known about VTE management in cancer patients but also what is done in Spanish hospitals in the clinical practice. The text summarizes the current knowledge and available evidence on the subject in Spain and provides a series of practical recommendations for CAT management and treatment algorithms to help clinicians to manage CAT over time.

Update on the management of older patients with pancreatic adenocarcinoma: a perspective from medical oncology.

In the context of pancreatic cancer, surgical intervention is typically recommended for localized tumours, whereas chemotherapy is the preferred approach in the advanced and/or metastatic setting. However, pancreatic cancer is closely linked to ageing, with an average diagnosis at 72 years. Paradoxically, despite its increased occurrence among older individuals, this population is often underrepresented in clinical studies, complicating the decision-making process. Age alone should not determine the therapeutic strategy but, given the high comorbidity and mortality of this disease, a comprehensive geriatric assessment (CGA) is necessary to define the best treatment, prevent toxicity, and optimize older patient care. In this review, a group of experts from the Oncogeriatrics Section of the Spanish Society of Medical Oncology (Sociedad Española de Oncología Médica, SEOM), the Spanish Cooperative Group for the Treatment of Digestive Tumours (Grupo Español de Tratamiento de los Tumores Digestivos, TTD), and the Multidisciplinary Spanish Group of Digestive Cancer (Grupo Español Multidisciplinar en Cáncer Digestivo, GEMCAD) have assessed the available scientific evidence and propose a series of recommendations on the management and treatment of the older population with pancreatic cancer.

Validation of the CoVID-TE model as a tool to predict thrombosis, bleeding, and mortality in the oncology patient with Sars-Cov-2 infection: a study by the SEOM cancer and thrombosis group

Purpose The CoVID-TE model was developed with the aim of predicting venous thrombotic events (VTE) in cancer patients with Sars-Cov-2 infection. Moreover, it was capable of predicting hemorrhage and mortality 30 days following infection diagnosis. The model is pending validation. Methods/patients Multicenter retrospective study (10 centers). Adult patients with active oncologic disease/ antineoplastic therapy with Sars-Cov-2 infection hospitalized between March 1, 2020 and March 1. 2022 were recruited. The primary endpoint was to study the association between the risk categories of the CoVID-TE model and the occurrence of thrombosis using the Chi-Square test. Secondary endpoints were to demonstrate the association between these categories and the occurrence of post-diagnostic Sars-Cov-2 bleeding/ death events. The Kaplan–Meier method was also used to compare mortality by stratification. Results 263 patients were enrolled. 59.3% were men with a median age of 67 years. 73.8% had stage IV disease and lung cancer was the most prevalent tumor (24%). A total of 86.7% had an ECOG 0–2 and 77.9% were receiving active antineoplastic therapy. After a median follow-up of 6.83 months, the incidence of VTE, bleeding, and death 90 days after Sars-Cov-2 diagnosis in the low-risk group was 3.9% (95% CI 1.9–7.9), 4.5% (95% CI 2.3–8.6), and 52.5% (95% CI 45.2–59.7), respectively. For the high-risk group it was 6% (95% CI 2.6–13.2), 9.6% (95% CI 5.0–17.9), and 58.0% (95% CI 45.3–66.1). The Chi-square test for trends detected no statistically significant association between these variables (p > 0.05). Median survival in the low-risk group was 10.15 months (95% CI 3.84–16.46), while in the high-risk group it was 3.68 months (95% CI 0.0–7.79). The differences detected were not statistically significant (p = 0.375) (AU)

Validation of the CoVID-TE model as a tool to predict thrombosis, bleeding, and mortality in the oncology patient with Sars-Cov-2 infection: a study by the SEOM cancer and thrombosis group.

PURPOSE: The CoVID-TE model was developed with the aim of predicting venous thrombotic events (VTE) in cancer patients with Sars-Cov-2 infection. Moreover, it was capable of predicting hemorrhage and mortality 30 days following infection diagnosis. The model is pending validation. METHODS/PATIENTS: Multicenter retrospective study (10 centers). Adult patients with active oncologic disease/ antineoplastic therapy with Sars-Cov-2 infection hospitalized between March 1, 2020 and March 1. 2022 were recruited. The primary endpoint was to study the association between the risk categories of the CoVID-TE model and the occurrence of thrombosis using the Chi-Square test. Secondary endpoints were to demonstrate the association between these categories and the occurrence of post-diagnostic Sars-Cov-2 bleeding/ death events. The Kaplan-Meier method was also used to compare mortality by stratification. RESULTS: 263 patients were enrolled. 59.3% were men with a median age of 67 years. 73.8% had stage IV disease and lung cancer was the most prevalent tumor (24%). A total of 86.7% had an ECOG 0-2 and 77.9% were receiving active antineoplastic therapy. After a median follow-up of 6.83 months, the incidence of VTE, bleeding, and death 90 days after Sars-Cov-2 diagnosis in the low-risk group was 3.9% (95% CI 1.9-7.9), 4.5% (95% CI 2.3-8.6), and 52.5% (95% CI 45.2-59.7), respectively. For the high-risk group it was 6% (95% CI 2.6-13.2), 9.6% (95% CI 5.0-17.9), and 58.0% (95% CI 45.3-66.1). The Chi-square test for trends detected no statistically significant association between these variables (p > 0.05). Median survival in the low-risk group was 10.15 months (95% CI 3.84-16.46), while in the high-risk group it was 3.68 months (95% CI 0.0-7.79). The differences detected were not statistically significant (p = 0.375). CONCLUSIONS: The data from our series does not validate of the CoVID-TE as a model to predict thrombosis, hemorrhage, or mortality in cancer patients with Sars-Cov-2 infection.

Integrating multiple spheres to identify the provenance and risk of urban dust and potentially toxic elements: Case study from central Mexico.

This study aims to improve the current method of studying potentially toxic elements (PTEs) in urban dust using direct chemical evidence (from dust, rock, and emission source samples) and robust geochemical methods. The provenance of urban dust was determined using rare earth elements (REEs) and geochemical diagrams (V-Ni-Th*10, TiO2 vs. Zr, and Zr/Ti vs. Nb/Y). The geogenic or anthropogenic source of PTEs was determined using the enrichment factor (EF) and compositional data analysis (CoDA), while a PTE's point emission source was identified using a 3.1*La-1.54*Ce-Zn diagram, mineralogy, and morphology analyses. The spatiotemporal distribution of PTEs was determined using a geographic information system, and their health risk (by inhalation) was estimated using a lung bioaccessibility test and particle size distribution. We collected urban dust (n = 38), rock (n = 4), and zinc concentrate (n = 2) samples and determined PTEs and REEs in a city of 1.25 million inhabitants in central Mexico. Results showed that urban dust derived from the San Miguelito Range. REEs, Sc, and Zr were geogenic, while Mn, Cu, Zn, As, and Pb were anthropogenic. Due to the presente of sphalerite particles, a zinc refinery was identified as the point emission source of Zn, As, and Pb. High concentrations of Zn (5000-20,008 mg/kg), As (120-284 mg/kg), and Pb (350-776 mg/kg) were found in urban dust near the zinc refinery. Additionally, particles of PM2.5 (66-84%), PM5.0 (13-27%), PM10 (3-8%), and PM20 (0-2%) and lung bioaccessibility of Sr (48.5-72.4%), Zn (9.6-28.4%), Cu (10.5-27.0%), Fe (4.5-8.6%), Mn (2.9-9.2%), Cr (38.3%) and Pb (30.6%) demonstrated a latent risk to human health. These approaches improve our understanding of the provenance of urban dust and its PTE emission sources in urban areas.

Clinicopathological Profiles Associated with Discordant RAS Mutational Status between Liquid and Tissue Biopsies in a Real-World Cohort of Metastatic Colorectal Cancer.

We aimed to identify common mCRC profiles associated with a discordant mutational status of RAS between the standard of care (SoC) tumour tissue tests and ctDNA tests to understand ctDNA detection and improve treatment responses. This was a multicentre, retrospective and prospective study. A total of 366 Spanish mCRC patients were independently recruited. BEAMing ddPCR technology was employed to detect ctDNA RAS mutations, and logistic regression analyses were performed to investigate clinicopathological factors associated with discordance. The highest concordance ratios were observed in profiles with multiple metastatic sites when the liver was present (89.7%; 95% CI 84.8-93.2), profiles with synchronous disease without primary tumour resection (90.2%; 95% CI 83.6-94.3) and profiles with mCRC originating in the left colon (91.3%; 95% CI 85.0-95.0). Metachronous disease originating in the right colon (OR = 6.1; 95% CI 1.7-26.5; p-value = 0.006) or rectum (OR = 5.0; 95% CI 1.5-17.8; p-value = 0.009) showed the highest probability of discrepancies. Primary tumour resection and a higher frequency of single metastases in the peritoneum or lungs in these patients were associated with reduced plasmatic mutation allele fractions (MAFs) and an increased probability of showing false-negative genotypes. Additional testing of patients with mCRC originating in the right colon or rectum with a single non-mutated ctDNA test is advised before the choice of therapy.

Bioaccumulation of titanium dioxide nanoparticles in green (Ulva sp.) and red (Palmaria palmata) seaweed.

A bioaccumulation study in red (Palmaria palmata) and green (Ulva sp.) seaweed has been carried out after exposure to different concentrations of citrate-coated titanium dioxide nanoparticles (5 and 25 nm) for 28 days. The concentration of total titanium and the number and size of accumulated nanoparticles in the seaweeds has been determined throughout the study by inductively coupled plasma mass spectrometry (ICP-MS) and single particle-ICP-MS (SP-ICP-MS), respectively. Ammonia was used as a reaction gas to minimize the effect of the interferences in the 48Ti determination by ICP-MS. Titanium concentrations measured in Ulva sp. were higher than those found in Palmaria palmata for the same exposure conditions. The maximum concentration of titanium (61.96 ± 15.49 µg g-1) was found in Ulva sp. after 28 days of exposure to 1.0 mg L-1 of 5 nm TiO2NPs. The concentration and sizes of TiO2NPs determined by SP-ICP-MS in alkaline seaweed extracts were similar for both seaweeds exposed to 5 and 25 nm TiO2NPs, which indicates that probably the element is accumulated in Ulva sp. mainly as ionic titanium or nanoparticles smaller than the limit of detection in size (27 nm). The implementation of TiO2NPs in Ulva sp. was confirmed by electron microscopy (TEM/STEM) in combination with energy dispersive X-Ray analysis (EDX).

Assessment of cardiotoxicity and plasma ropivacaine concentrations after serratus intercostal fascial plane block in an experimental model.

Serratus intercostal fascial plane block (SIFPB) has emerged as an alternative to paravertebral block in breast surgery. It involves the administration of high volumes and doses of local anesthetics (LA) that can potentially reach toxic levels. Ropivacaine is widely used in thoraco-fascial blocks; however, there is no information on the plasma concentrations attained after SIPFB and whether they are associated with cardiotoxicity. Plasma concentrations of ropivacaine and its electrophysiological effects were evaluated in eight pigs after bilateral SIFPB with ropivacaine in doses of 3 mg/kg. Plasma concentrations, electrophysiological and hemodynamic parameters were measured sequentially for the following 180 min until the end of the study. The area under the curve, the maximum plasma concentration (Cmax) and the time to reach Cmax (tmax) were calculated. The median arterial ropivacaine concentration Cmax was, 2.34 [1.40 to 3.74] µg/ml. The time to reach the highest concentration was 15 [10 to 20] min. Twenty-five percent of the animals had arterial concentrations above the lower limit concentration of ropivacaine for LA systemic toxicity (3.4 µg/ml). No alterations were observed in the electrophysiological or electrocardiographic parameters except for a prolongation of the QTc interval, from 489 ± 30 to 544 ± 44 ms (Δ11.38 ± 6%), P = 0.01. Hemodynamic parameters remained in the physiological range throughout the study. SIFPB with ropivacaine in doses of 3 mg/kg has reached potentially toxic levels, however, it has not been associated with adverse electrophysiological or hemodynamic effects.

Sodium bicarbonate reverts electrophysiologic cardiotoxicity of ropivacaine faster than lipid emulsions in a porcine model.

Ropivacaine has been described as a safer local anaesthetic (LA); however, serious cardiotoxic accidents have been reported. Intravenous-lipid-emulsion (ILE) therapy during LA intoxication seems to act as an antidote. Sodium bicarbonate is the standard treatment for sodium channel blocker drug toxicity. We compared both antidotes on the reversion of electrophysiologic toxicity induced by ropivacaine. Ropivacaine 5 mg kg-1 was administered in 24 pigs, and 3 min later, the animals received ILE: 1.5 ml kg-1  + 0.25 ml kg-1  min-1 (ILE group); sodium bicarbonate: 2 mEq kg-1  + 1 mEq kg-1  h-1 (NaHCO3 group); saline solution (CTL group). Electrophysiological parameters were evaluated for 30 min. The area under the curve (AUC) for the first 5 or 30 min was compared between groups. Ropivacaine induced a lengthening of the PR interval by 17% (P = 0.0001), His-ventricle-interval by 58% (P = 0.001), sinus QRS complex by 56% (P = 0.0001), paced QRS at 150 bpm by 257% (P = 0.0001), and at 120 bpm by 143% (P = 0.0001) in all groups. At 5 min after treatment, sinus QRS in the NaHCO3 group was shorter than that in the CTL group (AUCQRS5 , P = 0.003) or ILE group (AUCQRS5 , P = 0.045). During the first minute, seven of the animals in the NaHCO3 group vs. two in the ILE or 0 in the CTL group recovered more than 30% of the sinus QRS previously lengthened by ropivacaine (P = 0.003). Sodium bicarbonate reversed the electrophysiological toxicity of ropivacaine faster than ILE and control groups.

A genome-wide cell-free DNA methylation analysis identifies an episignature associated with metastatic luminal B breast cancer.

Breast cancers of the luminal B subtype are frequent tumors with high proliferation and poor prognosis. Epigenetic alterations have been found in breast tumors and in biological fluids. We aimed to profile the cell-free DNA (cfDNA) methylome of metastatic luminal B breast cancer (LBBC) patients using an epigenomic approach to discover potential noninvasive biomarkers. Plasma cfDNA was analyzed using the Infinium MethylationEpic array in a cohort of 14 women, including metastatic LBBC patients and nontumor controls. The methylation levels of cfDNA and tissue samples were validated with droplet digital PCR. The methylation and gene expression data of 582 primary luminal breast tumors and 79 nontumor tissues were obtained from The Cancer Genome Atlas (TCGA). We found an episignature of 1,467 differentially methylated CpGs that clearly identified patients with LBBC. Among the genes identified, the promoter hypermethylation of WNT1 was validated in cfDNA, showing an area under the ROC curve (AUC) of 0.86 for the noninvasive detection of metastatic LBBC. Both paired cfDNA and primary/metastatic breast tumor samples showed hypermethylation of WNT1. TCGA analysis revealed significant WNT1 hypermethylation in the primary tumors of luminal breast cancer patients, with a negative association between WNT1 methylation and gene expression. In this proof-of-principle study, we discovered an episignature associated with metastatic LBBC using a genome-wide cfDNA methylation approach. We also identified the promoter hypermethylation of WNT1 in cfDNA as a potential noninvasive biomarker for luminal breast cancer. Our results support the use of EPIC arrays to identify new epigenetic noninvasive biomarkers in breast cancer.

Proteomics reveals multiple effects of titanium dioxide and silver nanoparticles in the metabolism of turbot, Scophthalmus maximus.

Titanium dioxide (TiO2) and silver (Ag) NPs are among the most used engineered inorganic nanoparticles (NPs); however, their potential effects to marine demersal fish species, are not fully understood. Therefore, this study aimed to assess the proteomic alterations induced by sub-lethal concentrations citrate-coated 25 nm ("P25") TiO2 or polyvinylpyrrolidone (PVP) coated 15 nm Ag NPs to turbot, Scophthalmus maximus. Juvenile fish were exposed to the NPs through daily feeding for 14 days. The tested concentrations were 0, 0.75 or 1.5 mg of each NPs per kg of fish per day. The determination of NPs, Titanium and Ag levels (sp-ICP-MS/ICP-MS) and histological alterations (Transmission Electron Microscopy) supported proteomic analysis performed in the liver and kidney. Proteomic sample preparation procedure (SP3) was followed by LC-MS/MS. Label-free MS quantification methods were employed to assess differences in protein expression. Functional analysis was performed using STRING web-tool. KEGG Gene Ontology suggested terms were discussed and potential biomarkers of exposure were proposed. Overall, data shows that liver accumulated more elements than kidney, presented more histological alterations (lipid droplets counts and size) and proteomic alterations. The Differentially Expressed Proteins (DEPs) were higher in Ag NPs trial. The functional analysis revealed that both NPs caused enrichment of proteins related to generic processes (metabolic pathways). Ag NPs also affected protein synthesis and nucleic acid transcription, among other processes. Proteins related to thyroid hormone transport (Serpina7) and calcium ion binding (FAT2) were suggested as biomarkers of TiO2 NPs in liver. For Ag NPs, in kidney (and at a lower degree in liver) proteins related with metabolic activity, metabolism of exogenous substances and oxidative stress (e.g.: NADH dehydrogenase and Cytochrome P450) were suggested as potential biomarkers. Data suggests adverse effects in turbot after medium/long-term exposures and the need for additional studies to validate specific biological applications of these NPs.

Noninvasive early detection of colorectal cancer by hypermethylation of the LINC00473 promoter in plasma cell-free DNA.

BACKGROUND: Current noninvasive assays have limitations in the early detection of colorectal cancer. We evaluated the clinical utility of promoter methylation of the long noncoding RNA LINC00473 as a noninvasive biomarker to detect colorectal cancer and associated precancerous lesions. METHODS: We evaluated the epigenetic regulation of LINC00473 through promoter hypermethylation in colorectal cancer cell lines using bisulfite genomic sequencing and expression analyses. DNA methylation of LINC00473 was analyzed in primary colorectal tumors using 450K arrays and RNA-seq from The Cancer Genome Atlas (TCGA). Tissue-based findings were validated in several independent cohorts of colorectal cancer and advanced colorectal polyp patients by pyrosequencing. We explored the clinical utility of LINC00473 methylation for the early detection of colorectal cancer in plasma cell-free DNA by quantitative methylation-specific PCR and droplet digital PCR. RESULTS: LINC00473 showed transcriptionally silencing due to promoter hypermethylation in colorectal cancer cell lines and primary tumors. Methylation of the LINC00473 promoter accurately detected primary colorectal tumors in two independent clinical cohorts, with areas under the receiver operating characteristic curves (AUCs) of 0.94 and 0.89. This biomarker also identified advanced colorectal polyps from two other tissue-based clinical cohorts with high diagnostic accuracy (AUCs of 0.99 and 0.78). Finally, methylation analysis of the LINC00473 promoter in plasma cell-free DNA accurately identified patients with colorectal cancer and advanced colorectal polyps (AUCs of 0.88 and 0.84, respectively), which was confirmed in an independent cohort of patients. CONCLUSIONS: Hypermethylation of the LINC00473 promoter is a new promising biomarker for noninvasive early detection of colorectal cancer and related precancerous lesions.

Ultrasonication followed by enzymatic hydrolysis as a sample pre-treatment for the determination of Ag nanoparticles in edible seaweed by SP-ICP-MS.

Seaweed can bioaccumulate nanomaterials that would be transferred to the trophic chain. This work describes the optimization of a method for the separation of silver nanoparticles (AgNPs) from seaweed using an ultrasound-assisted enzymatic hydrolysis method and ulterior determination by single particle inductively coupled plasma mass spectrometry (SP-ICP-MS). The following parameters affecting the isolation of AgNPs were optimized using a Palmaria palmata (red seaweed) sample previously exposed to AgNPs: type of sonication (bath vs. ultrasonic probe), ultrasound amplitude, sonication time, sonication mode (pulsed vs. continuous sonication), concentration of the enzymes mixture (Macerozyme R-10®), and enzymatic hydrolysis time. The stability of AgNPs during extraction was tested by transmission electron microscopy (TEM) and using a standard of 15 nm of polyvinylpyrrolidone (PVP)-coated AgNPs analyzed by SP-ICP-MS. The analytical performance was evaluated with good results. For total Ag determination, the limits of detection and quantification were 2.2 and 7.7 ng g-1, respectively; and for AgNPs determination, the limits of detection in size and number were 14 nm and 4.34 × 107 part g-1, respectively. Besides, the matrix effect, the repeatability and the analytical recovery were also studied. Finally, the method was applied to the analysis of several red (Palmaria palmata) and green (Ulva sp.) seaweed samples.

Venous Thromboembolism In Cancer Patients: "From Evidence to Care".

This article seeks to review the current status of treatment and prevention of venous thromboembolic disease (VTE) in cancer patients after the addition of direct oral anticoagulants (DOAC) to the therapeutic arsenal available. The suitability of DOAC use in complex clinical situations, poorly represented in clinical trials, is controversial and difficult for care activity, making the recommendations in clinical practice guidelines the focus of special attention in this area. Recently, several randomized trials have compared low molecular weight heparin (LMWH) to DOAC for the management of CAT. Potential drug interactions with DOACs or the increased risk of bleeding in intraluminal tumors require special precautions, as do metastatic or primary brain disease and comorbid conditions, such as renal or liver failure, which are not suitably represented in pivotal studies. Furthermore, few data are available for situations involving elevated bleeding risk, with thrombocytopenia levels below the inclusion criterion of clinical trials, or recurrence during active anticoagulant therapy. Similarly, it is less clear that patients and physicians accept the presumption that oral DOAC administration is more convenient than subcutaneous LMWH, particularly when drug absorption may be compromised. The non-inclusion or under-representation of patients at higher risk for complications with anticoagulation in randomized clinical trials, makes their use complex in certain situations in health care. This paper provides a practical review of current clinical guideline recommendations regarding LMWH and/ or DOAC to treat and prevent CAT, as well as the most controversial clinical conditions for their use.

Clinical significance of baseline Pan-Immune-Inflammation Value and its dynamics in metastatic colorectal cancer patients under first-line chemotherapy.

Pan-Immune-Inflammation Value (PIV) has been recently proposed as a new blood-based prognostic biomarker in metastatic colorectal cancer (mCRC). Herein we aimed to validate its prognostic significance and to evaluate its utility for disease monitoring in patients with mCRC receiving first-line chemotherapy. We conducted a single-centre retrospective study involving 130 previously untreated mCRC patients under first-line standard chemotherapy in a real-world scenario. PIV was calculated as (neutrophil count × platelet count × monocyte count)/lymphocyte count at three different time-points: baseline, week 4 after therapy initiation, and at disease progression. We analyzed the influence of baseline PIV on overall survival (OS), progression-free survival (PFS), disease control rate (DCR), and overall response rate (ORR). We also explored the utility of PIV dynamics for disease monitoring. Baseline PIV high was significantly associated with worse OS in univariate [hazard ratio (HR) = 2.10, 95% CI, 1.41-3.15; p = 0.000299] and multivariate (HR = 1.82, 95% CI, 1.15-2.90; p = 0.011) analyses. Baseline PIV was also associated with worse PFS in univariate (HR = 2.04, 95% CI, 1.40-2.97; p = 0.000187) and multivariate (HR = 1.56, 95% CI, 1.05-2.31; p = 0.026) analyses. Baseline PIV was not correlated either with DCR or ORR. Regarding PIV dynamics, there was a statistically significant increase from week 4 to disease progression (p = 0.0003), which was at the expense of cases with disease control as best response (p < 0.0001). In conclusion, this study validates the prognostic significance of baseline PIV in patients with mCRC receiving first-line standard chemotherapy in a real-world scenario. Moreover, it suggests the potential utility of PIV monitoring to anticipate the disease progression among those patients who achieve initial disease control.

Titanium dioxide nanoparticles assessment in seaweeds by single particle inductively coupled plasma - Mass spectrometry.

In this study, a first attempt for isolating and determining (characterising) background levels of titanium dioxide nanoparticles (TiO2 NPs) in seaweed has been developed by using single particle inductively coupled plasma - mass spectrometry (SP-ICP-MS). Seaweeds were processed using an optimised ultrasound assisted extraction (UAE) procedure based on tetramethylammonium hydroxide (TMAH) before dilution and SP-ICP-MS analysis. The effect of the TMAH percentage in the extracting solution, as well as the volume of extracting solution and sonication (extraction) time, has been fully assessed. Additional experiments also showed that TiO2 NPs were quantitatively released from the seaweed matrix in one UAE step since the analysis of residues gave TiO2 NPs concentrations lower than the limit of quantification (LOQ) of the method. Validation of the method with 50 and 100 nm TiO2 NPs (10 µg L-1 as Ti) showed good analytical recovery (115% and 112% for 50 and 100 nm TiO2 NPs, respectively), and good reproducibility (2% for size and 16% for number of TiO2 NPs). Experiments regarding TiO2 NPs stability showed that the extracted NPs are stable since there were not changes on the number of TiO2 NPs and TiO2 NPs size distributions when exposing TiO2 NPs standards to the optimised extractive conditions.

Dynamic perspective of the neutrophil-to-lymphocyte ratio in metastatic gastric cancer.

PURPOSE: The neutrophil-to-lymphocyte ratio (NLR) is an accessible marker from a routine blood test. This study explored the prognostic and predictive value of a change in NLR (c-NLR) after chemotherapy, baseline NLR (bNLR) and chemotherapy response, in metastatic gastric cancer (mGC) patients. METHODS: A total of 116 mGC patients treated between 2009 to 2019 at seven hospitals from Galician Research Group on Digestive Tumors (GITuD) were reviewed in a multicentre, ambispective and observational study. NLR was calculated and the optimal cut-off was defined as NLR=3.96 based on ROC method. NLR was determined at baseline and after two chemotherapy cycles in first line treatment. Change NLR was calculated as NLR after two chemotherapy cycles minus bNLR. The relation of bNLR and c-NLR to overall survival (OS) was evaluated by Kaplan-Meier method and compared by log-rank test. Dynamic Score (DScore) based on c-NLR and baseline NLR were correlated with OS and radiological response. Univariate, multivariate and chi-square analyses were performed. RESULTS: Median patient age was 68.7 years, and 66% were male. Univariate analysis showed OS correlation for bNLR ≥3.96 (5.97 vs 10.87 months, p=0.001), c-NLR increase (6.63 vs 10.34 months, p=0.021) and DScore (12.74 vs 7.68 vs 2.43 months, p<0.001). High DScore was associated with radiological progression after two cycles (x2=10.26, p=0.006). Multivariate analysis: bNLR ≥3.96 (HR=2.16, p=0.003) and c-NLR increase (HR= 2.36, p=0.003) were prognostic factors of poor OS. CONCLUSION: High bNLR and increased NLR after chemotherapy were associated with worse outcome. Dynamic measurement of NLR provides information for stratifying patients to guide optimal treatment.

Evaluation of a Targeted Next-Generation Sequencing Panel for the Non-Invasive Detection of Variants in Circulating DNA of Colorectal Cancer.

Molecular profiling of circulating cell-free DNA (cfDNA) has shown utility for the management of colorectal cancer (CRC). TruSight Tumor 170 (TST170) is a next-generation sequencing (NGS) panel that covers 170 cancer-related genes, including KRAS, which is a key driver gene in CRC. We evaluated the capacity of TST170 to detect gene variants in cfDNA from a retrospective cohort of 20 metastatic CRC patients with known KRAS variants in tumor tissue and in cfDNA previously analyzed by pyrosequencing and BEAMing, respectively. The cfDNA of most of the patients (95%) was successfully sequenced. We frequently detected variants with clinical significance in KRAS (79%, 15/19) and PIK3CA (26%, 5/19) genes. Variants with potential clinical significance were also identified in another 27 cancer genes, such as APC. The type of KRAS variant detected in cfDNA by TST170 showed high concordance with those detected in tumor tissue (77%), and very high concordance with cfDNA analyzed by BEAMing (94%). The variant allele fractions for KRAS obtained in cfDNA by TST170 and BEAMing correlated strongly. This proof-of-principle study indicates that targeted NGS analysis of cfDNA with TST170 could be useful for non-invasive detection of gene variants in metastatic CRC patients, providing an assay that could be easily implemented for detecting somatic alterations in the clinic.