Unveiling inflammatory biomarkers in multibacillary leprosy: the role of lymphocyte-platelet ratio in predicting leprosy reactions.

Leprosy is a neglected contagious disease that causes physical disability and episodes of inflammation, called leprosy reactions. There are currently no consolidated laboratory markers that can predict or confirm the diagnosis of leprosy reactions, negatively impacting the progression of the disease. The aim of this study was to analyze the behavior of inflammatory biomarkers in a population of patients with multibacillary leprosy. This prospective study in a northeastern capital involved 67 new cases of multibacillary leprosy, assessing inflammatory biomarkers at diagnosis. Histopathology, qPCR, slit skin smear microscopy, and laboratory tests, including CRP-albumin, neutrophil-lymphocyte, lymphocyte-monocyte, platelet-lymphocyte ratios, and systemic immune-inflammation index, were conducted. Statistical analysis utilized Stata version 16.0®, employing Chi-square, Kruskal-Wallis, and Poisson regression (5% significance). The population, mainly young brown men with low socioeconomic status, borderline leprosy, and and degree of physical disability one, saw 19.4% experiencing leprosy reactions. Standard multibacillary multidrug therapy was administered to all. Ratios and index values exceeding medians were prevalent (46.3-47.8%). Assessing biological markers against leprosy reactions revealed a positive relation between reactions and lymphocyte-platelet ratio (p = 0.05) and a positive trend with the systemic immune-inflammation index (p = 0.06). Patients with reactions were 1.3 times more likely to exhibit an elevated lymphocyte-platelet ratio. The lymphocyte-platelet ratio emerged as a potential indicator for recognizing leprosy reactions. Further research is essential to validate these findings, aiming for earlier detection of leprosy reactions.

Blood bank quality control: pH assessment methods in platelet concentrates.

Platelet concentrates undergo progressive changes during storage, such as a decrease in pH. Additionally, pH and lactate production showed the strongest correlation with platelet survival in posttransfusion viability studies. pH measurement is a straightforward method for evaluating the quality control of blood components in blood bank practice. Our aim was to compare three pH assessment methods for canine platelet concentrates. The pH values of the canine platelet concentrates were assessed on the first day of storage using a calibrated pH meter, a portable gas analyzer and pH-indicator strips. The results from the pH meter and portable gas analyzer measurements were similar. The pH indicator strips presented higher average values compared to the other more reliable methods evaluated, which could result in the use of inadequate blood components. In conclusion, it is recommended to implement pH measurements using a pH meter for quality control in veterinary blood banks.

How Protein Depletion Balances Thrombosis and Bleeding Risk in the Context of Platelet's Activatory and Negative Signaling.

Platelets are small cell fragments that play a crucial role in hemostasis, requiring fast response times and fine signaling pathway regulation. For this regulation, platelets require a balance between two pathway types: the activatory and negative signaling pathways. Activatory signaling mediators are positive responses that enhance stimuli initiated by a receptor in the platelet membrane. Negative signaling regulates and controls the responses downstream of the same receptors to roll back or even avoid spontaneous thrombotic events. Several blood-related pathologies can be observed when these processes are unregulated, such as massive bleeding in activatory signaling inhibition or thrombotic events for negative signaling inhibition. The study of each protein and metabolite in isolation does not help to understand the role of the protein or how it can be contrasted; however, understanding the balance between active and negative signaling could help develop effective therapies to prevent thrombotic events and bleeding disorders.

Circulating platelets modulate oligodendrocyte progenitor cell differentiation during remyelination.

Revealing unknown cues that regulate oligodendrocyte progenitor cell (OPC) function in remyelination is important to optimise the development of regenerative therapies for multiple sclerosis (MS). Platelets are present in chronic non-remyelinated lesions of MS and an increase in circulating platelets has been described in experimental autoimmune encephalomyelitis (EAE) mice, an animal model for MS. However, the contribution of platelets to remyelination remains unexplored. Here we show platelet aggregation in proximity to OPCs in areas of experimental demyelination. Partial depletion of circulating platelets impaired OPC differentiation and remyelination, without altering blood-brain barrier stability and neuroinflammation. Transient exposure to platelets enhanced OPC differentiation in vitro, whereas sustained exposure suppressed this effect. In a mouse model of thrombocytosis (Calr+/-), there was a sustained increase in platelet aggregation together with a reduction of newly-generated oligodendrocytes following toxin-induced demyelination. These findings reveal a complex bimodal contribution of platelet to remyelination and provide insights into remyelination failure in MS.

Platelets isolation and ectonucleotidase assay: Revealing functional aspects of the communication between the vasculature and the immune system.

Platelets are enucleated fragments of cells with a diversity of internal granules. They are responsible for functions related to hemostasis, coagulation, and inflammation. The activation of these processes depends on a cascade coordinated by cytokines, chemokines, and components of purinergic signaling, such as ATP, ADP, and adenosine. Platelets express distinct components of the purinergic system: P2X1, P2Y1, PY12, and P2Y14 receptors; and the ectonucleotidases NTPDase, NPP, and 5NTE (ecto-5'-nucleotidase). Except for P2Y14, which has not yet exhibited a known function, all other components relate to the biological processes mentioned before. Platelets are known to display specific responses to microorganisms, being capable of recognizing pathogen-associated molecular patterns (PAMPs), engulfing certain classes of viruses, and participating in NETosis. Platelet function dysregulation implicates various pathophysiological processes, including cardiovascular diseases (CVDs) and infections. In COVID-19 patients, platelets exhibit altered purinergic signaling and increased activation, contributing to inflammation. Excessive platelet activation can lead to complications from thrombosis, which can affect the circulation of vital organs. Therefore, controlling the activation is necessary to end the inflammatory process and restore homeostasis. Ectonucleotidases, capable of hydrolyzing ATP, ADP, and AMP, are of fundamental importance in activating platelets, promising pharmacological targets for clinical use as cardiovascular protective drugs. In this review, we revisit platelet biology, the purinergic receptors and ectonucleotidases on their surface, and their importance in platelet activity. Additionally, we describe methods for isolating platelets in humans and murine, as well as the main techniques for detecting the activity of ectonucleotidases in platelets. Considering the multitude of functions revealed by platelets and their potential use as potent bioreactors able to secrete and present molecules involved in the communication of the vasculature with the immune system, it is crucial to deeply understand platelet biology and purinergic signaling participation to contribute to the developing of therapeutic strategies in diseases of the cardiovascular, inflammatory, and immune systems.

Analysis of the expression of cytokines and chemokines, platelet-leukocyte aggregates, sCD40L and sCD62P in cutaneous melanoma.

BACKGROUND: Cutaneous melanoma (CM) is a malignancy with a variable incidence worldwide and a poor advanced-stage prognosis. Melanoma growth is closely associated with the immune system. METHODS: A cross-sectional study was performed on CM patients admitted at the Hospital de Cancer de Pernambuco (HCP) between 2015 and 2018. Fifty-one CM patients were included, and 30 healthy individuals. The study aimed to evaluate the association of platelet activation mechanisms and inflammatory response in patients with cutaneous melanoma. RESULTS: Elevated serum IL10 and low serum TNF levels in CM patients compared to controls (p < 0.05). High IL6 levels in patients with negative lymph nodes LN (-) compared to positive lymph nodes group (LN +, p = 0.0005). Low RANTES levels in patients compared to controls (p < 0.05). Elevated levels of platelet-lymphocyte (PLA), platelet-monocytes (PMA), and platelet-neutrophils (PNA) aggregates were observed in patients compared to controls (p < 0.05). CM patients with stage II had lower PMA levels than stages I and III (p < 0.05). High PMA levels were observed in patients with LN (+) compared to the LN (-) group (p < 0.0001). Patients with SSM had high levels of sCD40L and sCD62P compared to controls (p < 0.05)). High sCD40L levels in stage II compared to the stage III group, and sCD62P in stages I and II compared to the stage III group (p < 0.05). High sCD62P levels in patients with LN (-) compared to the group LN (+) (p < 0.05). CONCLUSION: It was observed the immunosuppressive profile in CM may favor tumor progression. High levels of platelet-leukocyte aggregates, sCD40L, and sCD62P may be associated with the worst prognosis.

The polygenic implication of clopidogrel responsiveness: Insights from platelet reactivity analysis and next-generation sequencing.

Clopidogrel is widely used worldwide as an antiplatelet therapy in patients with acute coronary disease. Genetic factors influence interindividual variability in response. Some studies have explored the polygenic contributions in the drug response, generating pharmacogenomic risk scores (PgxPRS). Importantly, these factors are less explored in underrepresented populations, such as Latin-American countries. Identifying patients at risk of high-on-treatment platelet reactivity (HTPR) is highly valuable in translational medicine. In this study we used a custom next-generation sequencing (NGS) panel composed of 91 single nucleotide polymorphisms (SNPs) and 28 genes related to clopidogrel metabolism, to analyze 70 patients with platelet reactivity values, assessed through closure time (CT). Our results demonstrated the association of SNPs with HTPR and non-HTPR, revealing the strongest associations with rs2286823 (OR: 5,0; 95% CI: 1,02-24,48; p: 0,03), rs2032582 (OR: 4,41; 95% CI: 1,20-16,12; p: 0,019), and rs1045642 (OR: 3,38; 95% CI: 0,96-11,9; p: 0,05). Bivariate regression analysis demonstrated the significant association of several SNPs with the CT value, a "surrogate" biomarker of clopidogrel response. Exploratory results from the LASSO regression model showed a high discriminatory capacity between HTPR and non-HTPR patients (AUC: 0,955), and the generated PgxPRS demonstrated a significant negative association between the risk score, CT value, and the condition of HTPR and non-HTPR. To our knowledge, our study addresses for the first time the analysis of the polygenic contribution in platelet reactivity using NGS and establishes PgxPRS derived from the LASSO model. Our results demonstrate the polygenic implication of clopidogrel response and offer insights applicable to the translational medicine of antiplatelet therapy in an understudied population.

Antithrombotic Effect of Oil from the Pulp of Bocaiúva-Acrocomia aculeata (Jacq.) Lodd. ex Mart. (Arecaceae).

The study aimed to evaluate the antithrombotic action of Acrocomia aculeata pulp oil (AAPO) in natura, in an in vitro experimental model. AAPO was obtained by solvent extraction, and its chemical characterization was performed by gas chromatography coupled to a mass spectrometer (GC-MS). In vitro toxicity was evaluated with the Trypan Blue exclusion test and in vivo by the Galleria mellonella model. ADP/epinephrine-induced platelet aggregation after treatment with AAPO (50, 100, 200, 400, and 800 µg/mL) was evaluated by turbidimetry, and coagulation was determined by prothrombin activity time (PT) and activated partial thromboplastin time (aPTT). Platelet activation was measured by expression of P-selectin on the platelet surface by flow cytometry and intraplatelet content of reactive oxygen species (ROS) by fluorimetry. The results showed that AAPO has as major components such as oleic acid, palmitic acid, lauric acid, caprylic acid, and squalene. AAPO showed no toxicity in vitro or in vivo. Platelet aggregation decreased against agonists using treatment with different concentrations of AAPO. Oil did not interfere in PT and aPTT. Moreover, it expressively decreased ROS-induced platelet activation and P-selectin expression. Therefore, AAPO showed antiplatelet action since it decreased platelet activation verified by the decrease in P-selectin expression as well as in ROS production.

Evaluation of the quality of platelet concentrates obtained in a Peruvian hospital.

Introduction: Platelet concentrates are blood products obtained from donor's blood, and their conservation must be subject to a strict quality control process to guarantee a safe and high-performance product in treating diseases that require their use. Methods: We designed a cross-sectional study to determine the total compliance rate in platelet concentrates obtained in the blood bank of the Cayetano Heredia Hospital in Lima during November and December of 2019. The Buffy method Coat obtained the platelet concentrates, and parameters such as platelet count and residual leukocytes, pH, and swirling effect were evaluated according to the National Hemotherapy and Blood Bank Program criteria. Results: The platelet count had a mean of 6.66 ± 3.94 x 10¹°/µL, the platelet concentrates had a mean of 56.30 ± 6.22 mL, and all, without exception, had the presence of the Swirling phenomenon. The pH had a mean of 7.64 ± 0.15, while the leukocyte count had a mean of 4.22 ± 3.51 x 107/µL. Regarding compliance by the parameters evaluated, it was evident that the platelet and leukocyte count had moderate compliance rates of 43.6% and 24.1%, while the pH and swirling effect had rates of 100% in both cases. The total compliance rate was 54.9% (95% confidence interval: 46.0 to 63.5). Conclusions: The compliance rate of platelet concentrates is moderate, and it is necessary to implement a process of continuous quality improvement in the blood bank.

Introducción: Los concentrados plaquetarios son hemoderivados obtenidos de la sangre, y su conservación debe estar supeditada a un estricto proceso de control de calidad para garantizar un producto inocuo y de alto rendimiento en el tratamiento de enfermedades que requieran su uso. Métodos: Diseñamos un estudio transversal que tuvo por objetivo determinar la tasa de conformidad total en concentrados plaquetarios obtenidos en el banco de sangre del Hospital Cayetano Heredia de Lima durante los meses de noviembre y diciembre del año 2019. Los concentrados plaquetarios fueron obtenidos por el método de Buffy Coat y se evaluaron parámetros como el recuento de plaquetas y leucocitos residuales, pH y efecto swirling, según criterios del Programa Nacional de Hemoterapia y Bancos de Sangre. Resultados: El recuento de plaquetas tuvo una media de 6.66 ± 3.94 x1010/µL y los concentrados plaquetarios tuvieron una media de 56.30 ± 6.22 mL, y todos sin excepción tuvieron presencia de fenómeno Swirling. El pH tuvo una media de 7.64 ± 0.15, mientras que el recuento de leucocitos tuvo una media de 4.22 ± 3.51 x107/µL. En cuanto al cumplimiento por parámetro evaluado, se evidenció que el recuento de plaquetas y leucocitos tuvieron tasas de conformidad de 43.6% y 24.1%, mientras que el pH y efecto swirling tuvieron tasas del 100% en ambos casos. La tasa de conformidad total fue 54.9% (CI95%: 46.0 a 63.5). Conclusiones: La tasa de conformidad de los concentrados plaquetarios es moderada, y se requiere implementar un proceso de mejora continua de la calidad en el banco de sangre.

Altered dynamics of calcium fluxes and mitochondrial metabolism in platelet activation-related disease and aging.

Understanding the mechanisms controlling platelet function is crucial for exploring potential therapeutic targets related to atherothrombotic pathologies and primary hemostasis disorders. Our research, which focuses on the role of platelet mitochondria and Ca2+ fluxes in platelet activation, the formation of the procoagulant phenotype, and thrombosis, has significant implications for the development of new therapeutic strategies. Traditionally, Ca2+-dependent cellular signaling has been recognized as a determinant process throughout the platelet activation, controlled primarily by store-operated Ca2+ entry and the PLC-PKC signaling pathway. However, despite the accumulated knowledge of these regulatory mechanisms, the effectiveness of therapy based on various commonly used antiplatelet drugs (such as acetylsalicylic acid and clopidogrel, among others) has faced challenges due to bleeding risks and reduced efficacy associated with the phenomenon of high platelet reactivity. Recent evidence suggests that platelet mitochondria could play a fundamental role in these aspects through Ca2+-dependent mechanisms linked to apoptosis and forming a procoagulant phenotype. In this context, the present review describes the latest advances regarding the role of platelet mitochondria and Ca2+ fluxes in platelet activation, the formation of the procoagulant phenotype, and thrombosis.

The Biological Role of Platelet Derivatives in Regenerative Aesthetics.

Bioproducts derived from platelets have been extensively used across various medical fields, with a recent notable surge in their application in dermatology and aesthetic procedures. These products, such as platelet-rich plasma (PRP) and platelet-rich fibrin (PRF), play crucial roles in inducing blood vessel proliferation through growth factors derived from peripheral blood. PRP and PRF, in particular, facilitate fibrin polymerization, creating a robust structure that serves as a reservoir for numerous growth factors. These factors contribute to tissue regeneration by promoting cell proliferation, differentiation, and migration and collagen/elastin production. Aesthetic medicine harnesses these effects for diverse purposes, including hair restoration, scar treatment, striae management, and wound healing. Furthermore, these biological products can act as adjuvants with other treatment modalities, such as laser therapy, radiofrequency, and microneedling. This review synthesizes the existing evidence, offering insights into the applications and benefits of biological products in aesthetic medicine.

Association of neutrophil/lymphocyte and platelet/lymphocyte ratios with inflammation and survival in Mexican patients on chronic hemodialysis.

INTRODUCTION: Neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) are markers of systemic inflammatory status. The relationship between NLR, PLR, and mortality is controversial among hemodialysis (HD) patients. OBJECTIVE: Evaluate NLR and PLR in the prediction of mortality in chronic HD patients. MATERIALS AND METHODS: We analyzed 130 patients with a follow-up for 66 months. Four groups were established according to NLR-PLR values. Kaplan-Meier curves and Cox proportional hazards analysis were used. RESULTS: NLR-PLR correlated positively with C-reactive protein. Cox regression analysis for overall mortality among the four groups included age (HR 1.027, 95% CI 1.003-1.053) and albumin (HR 0.25, 95% CI 0.073-0.85). For cardiovascular (CV) mortality only pulse pressure differential (PPD) was included (HR 1.033; 95% CI 1.014-1.052). Low NLRs and high PLRs were associated with CV mortality (Log Rank test, p = 0.033). CONCLUSIONS: Low NLRs and high PLRs predict the risk of CV mortality among HD patients.

Prognostic value of systemic inflammation response indexes obtained from the complete blood count in patients treated for advanced ovarian carcinoma in front line.

OBJECTIVE: Various systemic inflammation response indexes (SIRI) have repeatedly been described as prognostic factors in ovarian cancer. They have not been validated in prospective trials and published results are sometimes contradictory. We aimed to explore their role in a cohort of patients diagnosed with stage III and IV ovarian cancer treated at our institution. METHODS: We retrospectively examined the prognostic influence of the neutrophil-to-lymphocyte ratio (NLR), the platelet-to-lymphocyte ratio (PLR), the monocyte-to-lymphocyte ratio (MLR), the red cell distribution width (RDW), and the mean platelet volume (MPV). RESULTS: A total of 77 patients were analyzed. NLR > 2.243 at diagnosis, NLR before primary surgery, MLR at diagnosis, PLR > 289.1 at diagnosis, and PLR at diagnosis were significant in univariate Cox regression for progression-free survival, but none of them retained their significance in the multivariate Cox regression analysis. For overall survival, NLR > = 2.53 at diagnosis, MLR > = 0.245 at diagnosis, and PLR > = 198.3 at diagnosis resulted significant in univariate COX regression; only PLR > = 198.3 at diagnosis retained its significance in the multivariate analysis. CONCLUSION: In our cohort, PLR > = 198.3 was an independent prognostic factor for worse OS. The definitive role of SIRI in ovarian cancer has not yet been established. If their value as prognostic factors could finally be established, they would become a simple and economical method to predict prognosis in patients with advanced ovarian cancer. Therefore, it is time to conduct prospective, multicenter studies with larger samples to definitively establish its role in ovarian cancer, if any.

Evaluation of the quality of platelet concentrates obtained in a Peruvian hospital / Evaluación de la calidad de concentrados de plaquetas obtenidos en un hospital peruano

INTRODUCTION: Platelet concentrates are blood products obtained from donor's blood, and their conservation must be subject to a strict quality control process to guarantee a safe and high-performance product in treating diseases that require their use. METHODS: We designed a cross-sectional study to determine the total compliance rate in platelet concentrates obtained in the blood bank of the Cayetano Heredia Hospital in Lima during November and December of 2019. The Buffy method Coat obtained the platelet concentrates, and parameters such as platelet count and residual leukocytes, pH, and swirling effect were evaluated according to the National Hemotherapy and Blood Bank Program criteria. RESULTS: The platelet count had a mean of 6.66 ± 3.94 x 10¹°/µL, the platelet concentrates had a mean of 56.30 ± 6.22 mL, and all, without exception, had the presence of the Swirling phenomenon. The pH had a mean of 7.64 ± 0.15, while the leukocyte count had a mean of 4.22 ± 3.51 x 107/µL. Regarding compliance by the parameters evaluated, it was evident that the platelet and leukocyte count had moderate compliance rates of 43.6% and 24.1%, while the pH and swirling effect had rates of 100% in both cases. The total compliance rate was 54.9% (95% confidence interval: 46.0 to 63.5). CONCLUSIONS: The compliance rate of platelet concentrates is moderate, and it is necessary to implement a process of continuous quality improvement in the blood bank.

INTRODUCCIÓN: Los concentrados plaquetarios son hemoderivados obtenidos de la sangre, y su conservación debe estar supeditada a un estricto proceso de control de calidad para garantizar un producto inocuo y de alto rendimiento en el tratamiento de enfermedades que requieran su uso. MÉTODOS: Diseñamos un estudio transversal que tuvo por objetivo determinar la tasa de conformidad total en concentrados plaquetarios obtenidos en el banco de sangre del Hospital Cayetano Heredia de Lima durante los meses de noviembre y diciembre del año 2019. Los concentrados plaquetarios fueron obtenidos por el método de Buffy Coat y se evaluaron parámetros como el recuento de plaquetas y leucocitos residuales, pH y efecto swirling, según criterios del Programa Nacional de Hemoterapia y Bancos de Sangre. RESULTADOS: El recuento de plaquetas tuvo una media de 6.66 ± 3.94 x1010/µL y los concentrados plaquetarios tuvieron una media de 56.30 ± 6.22 mL, y todos sin excepción tuvieron presencia de fenómeno Swirling. El pH tuvo una media de 7.64 ± 0.15, mientras que el recuento de leucocitos tuvo una media de 4.22 ± 3.51 x107/µL. En cuanto al cumplimiento por parámetro evaluado, se evidenció que el recuento de plaquetas y leucocitos tuvieron tasas de conformidad de 43.6% y 24.1%, mientras que el pH y efecto swirling tuvieron tasas del 100% en ambos casos. La tasa de conformidad total fue 54.9% (CI95%: 46.0 a 63.5). CONCLUSIONES: La tasa de conformidad de los concentrados plaquetarios es moderada, y se requiere implementar un proceso de mejora continua de la calidad en el banco de sangre.

Inflammatory biomarkers are correlated with thrombus burden in cerebral venous sinus thrombosis.

BACKGROUND: Increasing evidence suggests that inflammatory biomarkers play a significant role in cerebral venous sinus thrombosis (CVST). The neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and monocyte-to-lymphocyte ratio (MLR) are related to thrombotic conditions and indicators of systemic inflammation. OBJECTIVE: To analyze the correlation between inflammatory biomarkers and the extent of thrombus, determined by the CVST-Score. METHODS: A total of 40 patients with CVST (24 female subjects; 60%) and 40 age- and sex-matched healthy controls were retrospectively evaluated. Inflammatory biomarkers, including C-reactive protein (CRP), PLR, NLR, MLR, and the CVST-Score, were recorded to assess the relationship between biomarkers and thrombus burden. The patients were grouped according to symptom duration (group 1: 0-3 days; group 2: 4-7 days; and group 3: 8-30 days) to compare biomarker levels. RESULTS: The CRP, NLR, and PLR were significantly higher in the CVST group (p < 0.001; p = 0.003; p = 0.014 respectively). The NLR and PLR presented a significant positive correlation with the CVST-Score (p = 0.003, r = 0.464; p = 0.040, r = 0.326 respectively). The NLR was significantly higher in group 1 compared with groups 2 and 3 (p = 0.016 and p = 0.014 respectively). In group 1, there was a stronger positive correlation between the CVST-Score and the NLR (p = 0.026, r = 0.591) and the PLR (p = 0.012, r = 0.648). The multiple linear regression analysis revealed that the NLR is a key factor in predicting the CVST-Score (p = 0.019). CONCLUSION: The NLR and PLR are associated with thrombus burden in CVST, especially in patients admitted to the hospital in the early stages. The NLR is an independent factor to predict the thrombus burden in CVST.

ANTECEDENTES: Há evidências crescentes de que biomarcadores inflamatórios desempenham um papel importante na trombose venosa cerebral (TVC). A razão neutrófilo-linfócito (NLR), a razão plaqueta-linfócito (PLR) e a razão monócito-linfócito (MLR) estão relacionadas a condições trombóticas e são indicadores de inflamação sistêmica. OBJETIVO: Analisar a correlação entre NLR, PLR, MLR e a extensão do trombo, determinada pelo escore de TVC. MéTODOS: Avaliamos retrospectivamente 40 pacientes com TVC (24 mulheres; 60%) e 40 controles pareados por idade e sexo. Biomarcadores inflamatórios, incluindo proteína C reativa (PCR), PLR, NLR, MLR e escore de TVC, foram registrados para avaliar a relação entre biomarcadores e carga trombótica. Os pacientes foram agrupados de acordo com a duração dos sintomas (grupo 1: 0­3 dias; grupo 2: 4­7 dias; e grupo 3: 8­30 dias) para a comparação dos níveis de biomarcadores. RESULTADOS: A PCR, a NLR e a PLR foram significativamente maiores no grupo com TVC (p < 0,001; p = 0,003; e p = 0,014, respectivamente). A NLR e a PLR apresentaram correlação positiva significativa com o escore de TVC (p = 0,003, r = 0,464; e p = 0,040, r = 0,326, respectivamente). A NLR foi significativamente maior no grupo 1 em comparação aos grupos 2 e 3 (p = 0,016 e p = 0,014, respectivamente). No grupo 1, houve correlação mais forte entre o escore de TVC e a NLR (p = 0,026, r = 0,591) e a PLR (p = 0,012, r = 0,648). A análise de regressão linear múltipla identificou a NLR como fator-chave na predição do escore de TVC (p = 0,019). CONCLUSãO: A NLR e a PLR estão associadas à carga trombótica na TVC, especialmente em pacientes admitidos precocemente, e a RNL é um fator independente na previsão da carga trombótica.

Prognostic nomogram based on pre-treatment HALP score for patients with advanced non-small cell lung cancer.

BACKGROUND: To explore the correlation of pre-treatment Hemoglobin-Albumin-Lymphocyte-Platelet (HALP) score with the prognosis of patients with advanced Non-Small Cell Lung Cancer (NSCLC) undergoing first-line conventional platinum-based chemotherapy. METHODS: In this retrospective cohort study, 203 patients with advanced NSCLC were recruited from January 2017 to December 2021. The cut-off value for the HALP score was determined by Receiver Operating Characteristic (ROC) curve analysis. The baseline characteristics and blood parameters were recorded, and the Log-rank test and Kaplan-Meier curves were applied for the survival analysis. In the univariate and multivariate analyses, the Cox regression analysis was carried out. The predictive accuracy and discriminative ability of the nomogram were determined by the Concordance index (C-index) and calibration curve and compared with a single HALP score by ROC curve analysis. RESULTS: The optimal cut-off value for the HALP score was 28.02. The lower HALP score was closely associated with poorer Progression-Free Survival (PFS) and Overall Survival (OS). The male gender and other pathological types were associated with shorter OS. Disease progression and low HALP were correlated with shorter OS and PFS. In addition, nomograms were established based on HALP scores, gender, pathology type and efficacy rating, and used to predict OS. The C-index for OS prediction was 0.7036 (95% CI 0.643 to 0.7643), which was significantly higher than the C-index of HALP at 6-, 12-, and 24-months. CONCLUSION: The HALP score is associated with the prognosis of advanced NSCLC patients receiving conventional platinum-based chemotherapy, and the nomogram established based on the HALP score has a better predictive capability for OS.

Relationship between platelet-related parameters and new-onset atrial fibrillation after coronary bypass surgery.

OBJECTIVE: Inflammation plays a key role in the pathogenesis of postoperative atrial fibrillation after coronary artery bypass graft surgery. In this study, we aimed to investigate the changes in mean platelet volume and platelet values during the spring and autumn seasons in patients who underwent isolated coronary artery bypass graft surgery and the possible effect of these occurrences on postoperative atrial fibrillation. METHODS: Consecutive patients who underwent elective isolated coronary bypass surgery at our clinic in the spring and autumn months, between August 2020 and July 2022, were retrospectively included in this study. Variables were evaluated according to the spring and autumn seasons. Patients who did not develop in-hospital postoperative atrial fibrillation were identified as Group 1, and those who did constituted Group 2. RESULTS: A total of 622 patients were included in the study. The patients were divided into two groups: those who were operated on in the spring (n=277, median age=62 years, male gender ratio=77.3%) and those who were operated on in the autumn (n=345, median age=61 years, male gender ratio=81.4%). There was no statistically significant difference between the patients operated on in both seasons in terms of age, gender, hypertension rates, and the frequency of chronic obstructive pulmonary disease. In multivariate analysis, being over 70 years old (OR: 1.934, 95% confidence interval (CI) 1.489-2.995, p<0.001), having a left ventricular ejection fraction below 30% (OR: 1.550, 95%CI 1.190-2.236, p=0.012), and having chronic obstructive pulmonary disease (OR: 1.663, 95%CI 1.339-2.191, p<0.001) were found to be independent predictors in predicting the development of postoperative atrial fibrillation. CONCLUSION: In this study, we first demonstrated that mean platelet volume and platelet mass index values were higher in patients in the autumn months. Additionally, for the first time in the literature, we showed that there is a significant relationship between platelet mass index value and the development of postoperative atrial fibrillation in patients who underwent isolated coronary artery bypass graft.

Non-clinical investigations about cytotoxic and anti-platelet activities of gamma-terpinene.

Gamma-terpinene (γ-TPN) is a cyclohexane monoterpene isolated from plant essential oils, such as tea tree (Melaleuca alternifolia), oregano (Origanum vulgare), rosemary (Rosmarinus officinalis L.), thyme (Thymus vulgaris Marchand), and eucalyptus (Eucalyptus sp.). Terpenes are widely studied molecules pharmacologically active on the cardiovascular system, hemostasis, and antioxidant actions. Herein, it was investigated the cytotoxic and antiplatelet activity of γ-TPN using different non-clinical laboratory models. For in silico evaluation, the PreADMET, SwissADME, and SwissTargetPrediction softwares were used. Molecular docking was performed using the AutoDockVina and BIOVIA Discovery Studio databases. The cytotoxicity of γ-TPN was analyzed by the MTT assay upon normal murine endothelial SVEC4-10 and fibroblast L-929 cells. Platelet aggregation was evaluated with platelet-rich (PRP) and platelet-poor (PPP) plasma from spontaneously hypertensive rats (SHR), in addition to SVEC4-10 cells pre-incubated with γ-TPN (50, 100, and 200 µM) for 24 h. SHR animals were pre-treated by gavage with γ-TPN for 7 days and divided into four groups (negative control, 25, 50, and 100 mg/kg). Blood samples were collected to measure nitrite using the Griess reagent. Gamma-TPN proved to be quite lipid-soluble (Log P = +4.50), with a qualified profile of similarity to the drug, good bioavailability, and adequate pharmacokinetics. It exhibited affinity mainly for the P2Y12 receptor (6.450 ± 0.232 Kcal/mol), moderate cytotoxicity for L-929 (CC50 = 333.3 µM) and SVEC 4-10 (CC50 = 366.7 µM) cells. The presence of γ-TPN in SVEC 4-10 cells was also able to reduce platelet aggregation by 51.57 and 44.20% at lower concentrations (50 and 100 µM, respectively). Then, γ-TPN has good affinity with purinergic receptors and an effect on the reversal of platelet aggregation and oxidative stress, being promising and safe for therapeutic targets and subsequent studies on the control of thromboembolic diseases.