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Circulating tumor cells (CTCs) enumeration and molecular profiling hold promise in revolutionizing the management of solid tumors. Their understanding has evolved significantly over the past two decades, encompassing pivotal biological discoveries and clinical studies across various malignancies. While for some tumor types, such as breast, prostate, and colorectal cancer, CTCs are ready to enter clinical practice, for others, additional research is required. CTCs serve as versatile biomarkers, offering insights into tumor biology, metastatic progression, and treatment response. This review summarizes the latest advancements in CTC research and highlights future directions of investigation. Special attention is given to concurrent evaluations of CTCs and other circulating biomarkers, particularly circulating tumor DNA. Multi-analyte assessment holds the potential to unlock the full clinical capabilities of liquid biopsy. In conclusion, CTCs represent a transformative biomarker in precision oncology, offering extraordinary opportunities to translate scientific discoveries into tangible improvements in patient care.
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Objetivo: Los pacientes con enfermedad renal crónica (ERC) en hemodiálisis (HD) suelen presentar déficits cognitivos. Sin embargo, existen pocos estudios que hayan examinado el funcionamiento neuropsicológico de aquellos que reciben diálisis peritoneal (DP). Método: Se evaluaron las funciones ejecutivas, la velocidad de procesamiento y la memoria verbal en 27 pacientes en DP, 42 en HD y 42 participantes sanos (PS). La presión sanguínea sistólica y el tiempo total en terapia renal sustitutiva (TRS) se controlaron estadísticamente. Las asociaciones entre el rendimiento y los factores clínicos se analizaron mediante correlaciones y regresión múltiple. Resultados: El grupo DP presentó mejor ejecución respecto al HD en fluidez verbal, memoria de trabajo, flexibilidad cognitiva, planificación y toma de decisiones. El grupo DP mostró peor ejecución que el grupo PS en inhibición y memoria verbal. Las puntuaciones en las funciones ejecutivas se asociaron positivamente con los meses totales en DP, en TRS, en HD, la albúmina, el colesterol total y el fósforo, y de forma negativa con la ferritina. Conclusión: El funcionamiento ejecutivo global fue mejor en los pacientes en DP que en aquellos en HD. Los resultados muestran el efecto positivo de la DP sobre las funciones ejecutivas, lo que debe tenerse en cuenta a la hora de la elección de la TRS. Las asociaciones observadas entre los factores bioquímicos y el rendimiento muestran la importancia de mantener un adecuado estado nutricional en estos pacientes.(AU)
Background: Patients with chronic kidney disease on hemodialysis (HD) often have cognitive deficits. However, there are few studies that have examined the neuropsychological impairments of patients receiving peritoneal dialysis (PD). Methods: Executive functions, processing speed and verbal memory were assessed in 27 PD patients, 42 HD patients, and 42 healthy participants (HP). Systolic blood pressure and total time on renal replacement therapy (RRT) were controlled statistically. Associations between performance and clinical factors were analyzed using correlations and multiple regression. Results: The DP group showed better performance compared to the HD group in verbal fluency, working memory, cognitive flexibility, planning and decision making. The DP group showed worse execution than the HP group in verbal inhibition and memory. Executive function scores were positively associated with total months on PD, total months on RRT, total months on HD, albumin, total cholesterol, and phosphorus, and negatively with ferritin. Conclusion: Global executive functioning was more optimal in PD patients than in HD patients. The results show the positive effect of PD on executive functions, which must be taken into account when choosing the TRS. The associations observed between biochemical factors and performance show the importance of maintaining an adequate nutritional status in these patients.(AU)
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Humanos , Masculino , Femenino , Persona de Mediana Edad , Diálisis Peritoneal , Insuficiencia Renal Crónica/complicaciones , Función Ejecutiva , Diálisis Renal , Pruebas Neuropsicológicas , Disfunción Cognitiva , Medicina Clínica , Estudios de Casos y Controles , Neuropsicología , MemoriaRESUMEN
BACKGROUND: Patients with chronic kidney disease on hemodialysis (HD) often have cognitive deficits. However, there are few studies that have examined the neuropsychological impairments of patients receiving peritoneal dialysis (PD). METHODS: Executive functions, processing speed and verbal memory were assessed in 27 PD patients, 42 HD patients, and 42 healthy participants (HP). Systolic blood pressure and total time on renal replacement therapy (RRT) were controlled statistically. Associations between performance and clinical factors were analyzed using correlations and multiple regression. RESULTS: The DP group showed better performance compared to the HD group in verbal fluency, working memory, cognitive flexibility, planning and decision making. The DP group showed worse execution than the HP group in verbal inhibition and memory. Executive function scores were positively associated with total months on PD, total months on RRT, total months on HD, albumin, total cholesterol, and phosphorus, and negatively with ferritin. CONCLUSION: Global executive functioning was more optimal in PD patients than in HD patients. The results show the positive effect of PD on executive functions, which must be taken into account when choosing the TRS. The associations observed between biochemical factors and performance show the importance of maintaining an adequate nutritional status in these patients.
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Fallo Renal Crónico , Diálisis Peritoneal , Insuficiencia Renal Crónica , Humanos , Fallo Renal Crónico/terapia , Diálisis Peritoneal/efectos adversos , Diálisis Renal/efectos adversos , Diálisis Renal/métodos , Diálisis Renal/psicología , Insuficiencia Renal Crónica/complicaciones , Insuficiencia Renal Crónica/terapia , Terapia de Reemplazo RenalRESUMEN
Concurrent chemoradiotherapy (cCRT) is the mainstay of treatment for patients diagnosed with locally advanced non-small cell lung cancer (NSCLC). One significant challenge in the effectiveness of this therapy is the potential development of resistance mechanisms, where autophagy up-regulation has been proposed as a key contributing factor. However, there is a lack of reliable biomarkers to predict outcomes on these patients. Interestingly, for addressing this gap, extracellular vesicles (EVs) and circulating tumor cells (CTCs) have emerged as potential sources of such biomarkers. In this study, we investigated EV-associated miRNAs and presence of autophagic CTCs in prospectively collected serial samples from 38 patients with stage III NSCLC undergoing cCRT. Our findings revealed that non-responders exhibited low levels of baseline EV miR-375, miR-200c, and miR-30c. In particular, EV miR-30c showed high predictive value with an area under the curve of 87.2%. Low EV miR-30c and the presence of autophagic-activated CTCs emerged as independent predictive biomarkers for shorter relapse-free survival and overall survival. Furthermore, in experimental models simulating the effects of chemo- and radiotherapy, the administration of miR-30c, either through direct transfection or encapsulation into human EVs, led to the inhibition of autophagy in these cells. This is the first report demonstrating that EV miR-30c inhibits tumor autophagy and its quantification, together with autophagic-activated CTCs, could be used as biomarkers for the stratification and monitoring of patients with NSCLC undergoing cCRT, and they may hold promising potential for guiding subsequent consolidation treatment with immunotherapy or other novel therapies based on autophagy inhibitors.
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Cancer interception (CI) is a new approach to cancer prevention and treatment in a cancer-risk population that aims to detect and treat pre-tumoral stages. It has several potential advantages over traditional cancer diagnosis and monitoring methods because it is non-invasive, making it less painful and risky than conventional biopsy procedures. The circulating tumor cells (CTCs), liquid biopsy family members, are essential for the CI approach; then, the liquid biopsy (LB) is used as a CI tool. LB can be performed frequently because of its easy sampling and early pathological stages, which allow repeated non-invasive monitoring of cancer progression and response to treatment. CTCs have been found in the bloodstream of several types of cancer patients, including in early-stage cancer and premalignant lesions, suggesting a tumor development role in cancer's early stages. This chapter will present foundational scientific studies addressing CI and the clinical impact of CTC screening in a population at risk for cancer.
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Células Neoplásicas Circulantes , Humanos , Factores de RiesgoRESUMEN
Introduction: Infections caused by carbapenem-resistant Enterobacterales (CRE) and carbapenem-resistant Pseudomonas aeruginosa, including isolates producing acquired carbapenemases, constitute a prevalent health problem worldwide. The primary objective of this study was to determine the distribution of the different carbapenemases among carbapenemase-producing Enterobacterales (CPE, specifically Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae complex, and Klebsiella aerogenes) and carbapenemase-producing P. aeruginosa (CPPA) in Spain from January 2014 to December 2018. Methods: A national, retrospective, cross-sectional multicenter study was performed. The study included the first isolate per patient and year obtained from clinical samples and obtained for diagnosis of infection in hospitalized patients. A structured questionnaire was completed by the participating centers using the REDCap platform, and results were analyzed using IBM SPSS Statistics 29.0.0. Results: A total of 2,704 carbapenemase-producing microorganisms were included, for which the type of carbapenemase was determined in 2692 cases: 2280 CPE (84.7%) and 412 CPPA (15.3%), most often using molecular methods and immunochromatographic assays. Globally, the most frequent types of carbapenemase in Enterobacterales and P. aeruginosa were OXA-48-like, alone or in combination with other enzymes (1,523 cases, 66.8%) and VIM (365 cases, 88.6%), respectively. Among Enterobacterales, carbapenemase-producing K. pneumoniae was reported in 1821 cases (79.9%), followed by E. cloacae complex in 334 cases (14.6%). In Enterobacterales, KPC is mainly present in the South and South-East regions of Spain and OXA-48-like in the rest of the country. Regarding P. aeruginosa, VIM is widely distributed all over the country. Globally, an increasing percentage of OXA-48-like enzymes was observed from 2014 to 2017. KPC enzymes were more frequent in 2017-2018 compared to 2014-2016. Discussion: Data from this study help to understand the situation and evolution of the main species of CPE and CPPA in Spain, with practical implications for control and optimal treatment of infections caused by these multi-drug resistant organisms.
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INTRODUCCIÓN: Los Servicios de Salud Públicos de la Región Metropolitana (RM) cuentan con 9 camas psiquiátricas de corta estadía por 100.000 habitantes adultos, por debajo de las recomendaciones internacionales. OBJETIVO: El presente estudio evaluará la capacidad de resolución del principal Servicio de Urgencias Psiquiátricas de la RM lo que puede ser de utilidad para evaluar el impacto de la disponibilidad de camas de corta estadía en la RM. MATERIALES Y MÉTODO: Se realizó un estudio observacional retrospectivo de todas las atenciones realizadas en el Servicio de Urgencias del Instituto Psiquiátrico "Dr. José Horwitz B." entre los años 2017 y 2020 y las indicaciones de hospitalización y su resolución. Se obtuvieron Razones de Tasas de Incidencia crudas y ajustadas para la indicación de hospitalización, las efectuadas y aquellas rechazadas por falta de vacantes. RESULTADOS: Se realizaron 90.464 atenciones a 41.541 usuarios y se indicó la hospitalización al 12,5% de ellas. La hospitalización se efectúa en el 59,5% de las atenciones y 35,9% no se pueden realizar por falta de vacantes. Al comparar las Tasas de Incidencia ajustadas se observó solamente una mayor tasa de hospitalización efectuada para los usuarios de regiones (IRR = 1,27; IC95%: 1,11-1,44; valor-p < 0,001) y durante el primer semestre de 2020 (IRR = 1,49; IC95%: 1,35-1,65; valor-p < 0,001). CONCLUSIONES: La evidente demanda por las hospitalizaciones psiquiátricas y la baja disponibilidad de camas de corta estadía en la Región Metropolitana probablemente tiene consecuencias insospechadas. Su abordaje es un desafío que requiere de una planificación multinivel entre todos los actores involucrados.
BACKGROUND: The Public Health Services at the Metropolitan Region (MR) of Chile have nine acute psychiatric beds per 100,000 inhabitants, under international recommendations. AIM: The present study will evaluate the resolution capacity of the main MR Psychiatric Emergency Room (PER), which may help assess the impact of the availability of acute beds in the MR. MATERIAL AND METHODS: A retrospective observational study of electronic patient records for all adult patients attending PER of the Psychiatric Institute "Dr. José Horwitz B." between 2017 and 2020 was analyzed. Crude and adjusted Incidence Rate Ratios were obtained for the indication of hospitalization, admissions, and those rejected due to lack of acute psychiatric beds. RESULTS: 90,464 attendances were evaluated on 41,541 patients, and hospitalization was indicated for 12.5% of them. Admissions were carried out in 59.5%, and 35.9% did not occur due to a lack of acute psychiatric beds. When comparing the adjusted Incidence Rates, only a higher hospitalization rate was observed for users from regions (IRR = 1,267; 95% CI: 1,11-1,44; p-value < 0.001) and during the first half of 2020 (IRR = 1.49; CI95%: 1.35-1.65; p-value < 0.001). CONCLUSIONS: The demand for psychiatric hospitalizations and the low availability of acute psychiatric beds in the MR probably have unsuspected consequences. The solution requires multilevel planning among all the actors involved.
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Humanos , Masculino , Femenino , Adolescente , Adulto , Persona de Mediana Edad , Anciano , Adulto Joven , Capacidad de Camas en Hospitales/estadística & datos numéricos , Hospitalización/estadística & datos numéricos , Chile/epidemiología , Estudios Retrospectivos , Necesidades y Demandas de Servicios de Salud/estadística & datos numéricos , Trastornos Mentales/terapia , Trastornos Mentales/epidemiologíaRESUMEN
miRNAs have been widely identified as important players in cancer development and progression. Metastasis in breast cancer can occur as relapse of a treated primary tumour or at the time of diagnosis of the tumour. The aim of this review is to show if both metastasis are different molecular entities characterised by different miRNA signatures that could be studied as specific biomarkers for each entity. For this, we systematically searched the PubMed, Scopus and Web of Science databases. After searching and reviewing the literature, a total of 30 records were included in this review. Results showed a genetic signature including a total of 5 upregulated miRNAs in metastasis compared with early stages. Of them, miR-23b and miR-200c were exclusively present in relapse metastasis. Finally, we proposed a molecular signature for future studies that can be used as a complementary tool at clinical trials for the diagnosis and characterization of metastasis.
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Neoplasias de la Mama , MicroARNs , Humanos , Femenino , MicroARNs/genética , Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Perfilación de la Expresión Génica/métodos , Enfermedad Crónica , Recurrencia , Biomarcadores de Tumor/genética , Regulación Neoplásica de la Expresión Génica , Metástasis de la NeoplasiaRESUMEN
BACKGROUND Cognitive problems are frequent in patients with end-stage renal disease (ESRD) treated with hemodialysis. However, previous studies used only a single cognitive screening test or a small number of cognitive indices, which is inadequate for an exhaustive evaluation of cognitive deficits. This case-control study aimed to evaluate cognitive function in patients with ESRD before and after hemodialysis at centers in southern Spain, and included analysis of associations between cognitive function and duration of hemodialysis, biochemistry, body composition, and treatment variables. MATERIAL AND METHODS Cognitive performance was evaluated in 42 healthy participants (HPs) and in 43 ESRD patients, before and after hemodialysis. The tests measured verbal and visual memory, sustained/selective attention, and processing speed. The diagnostic criterion for ESRD was a glomerular filtration rate.
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Fallo Renal Crónico , Humanos , Estudios de Casos y Controles , España , Fallo Renal Crónico/complicaciones , Fallo Renal Crónico/terapia , Diálisis Renal , CogniciónRESUMEN
Circulating Tumor Cells (CTCs) are considered a prognostic marker in pancreatic cancer. In this study we present a new approach for counting CTCs and CTC clusters in patients with pancreatic cancer using the IsofluxTM System with the Hough transform algorithm (Hough-IsofluxTM). The Hough-IsofluxTM approach is based on the counting of an array of pixels with a nucleus and cytokeratin expression excluding the CD45 signal. Total CTCs including free and CTC clusters were evaluated in healthy donor samples mixed with pancreatic cancer cells (PCCs) and in samples from patients with pancreatic ductal adenocarcinoma (PDAC). The IsofluxTM System with manual counting was used in a blinded manner by three technicians who used Manual-IsofluxTM as a reference. The accuracy of the Hough-IsofluxTM approach for detecting PCC based on counted events was 91.00% [84.50, 93.50] with a PCC recovery rate of 80.75 ± 16.41%. A high correlation between the Hough-IsofluxTM and Manual-IsofluxTM was observed for both free CTCs and for clusters in experimental PCC (R2 = 0.993 and R2 = 0.902 respectively). However, the correlation rate was better for free CTCs than for clusters in PDAC patient samples (R2 = 0.974 and R2 = 0.790 respectively). In conclusion, the Hough-IsofluxTM approach showed high accuracy for the detection of circulating pancreatic cancer cells. A better correlation rate was observed between Hough-IsofluxTM approach and with the Manual-IsofluxTM for isolated CTCs than for clusters in PDAC patient samples.
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Carcinoma Ductal Pancreático , Células Neoplásicas Circulantes , Neoplasias Pancreáticas , Humanos , Biomarcadores de Tumor/metabolismo , Carcinoma Ductal Pancreático/patología , Células Neoplásicas Circulantes/patología , Neoplasias Pancreáticas/patología , Algoritmos , Neoplasias PancreáticasRESUMEN
In this work, we present a microfluidic amperometric immunosensor for cancer biomarker claudin7 (CLD7) determination in circulating extracellular vesicles (EVs) as well as its validation in colorectal cancer (CC) patients. The device is based on synthetized nanosized MIL-125-NH2 particles, covalently anchored to the central channel of the microfluidic immunosensor. This nanomaterial was employed as efficient platform for anti-CLD7 monoclonal antibodies immobilization for specifically recognize and capture CLD7 in EVs samples. Afterwards, the amount of this trapped CLD7 was quantified by HRP-conjugated anti-CLD7-antibody. HRP reacted with its enzymatic substrate in a redox process which resulted in the appearance of a current whose magnitude was directly proportional to the level of CLD7 in the sample. This immunosensor, under optimum conditions, gave the limit of detection for CLD7 of 0.1 pg mL-1, with a wide linear range from 2 to 1000 pg mL-1. The results reported herein open up the use of porous open framework platforms for sensing applications for biomedicine and diagnosis.
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Técnicas Biosensibles , Neoplasias Colorrectales , Nanoestructuras , Anticuerpos Monoclonales , Biomarcadores de Tumor , Técnicas Biosensibles/métodos , Neoplasias Colorrectales/diagnóstico , Técnicas Electroquímicas , Humanos , Inmunoensayo/métodos , Límite de Detección , Microfluídica/métodos , PorosidadRESUMEN
BACKGROUND: Immune-checkpoint inhibitors (ICIs) are an effective therapeutic strategy, improving the survival of patients with lung cancer compared with conventional treatments. However, novel predictive biomarkers are needed to stratify which patients derive clinical benefit because the currently used and highly heterogenic histological PD-L1 has shown low accuracy. Liquid biopsy is the analysis of biomarkers in body fluids and represents a minimally invasive tool that can be used to monitor tumor evolution and treatment effects, potentially reducing biases associated with tumor heterogeneity associated with tissue biopsies. In this context, cytokines, such as transforming growth factor-ß (TGF-ß), can be found free in circulation in the blood and packaged into extracellular vesicles (EVs), which have a specific delivery tropism and can affect in tumor/immune system interaction. TGF-ß is an immunosuppressive cytokine that plays a crucial role in tumor immune escape, treatment resistance, and metastasis. Thus, we aimed to evaluate the predictive value of circulating and EV TGF-ß in patients with non-small-cell lung cancer receiving ICIs. METHODS: Plasma samples were collected in 33 patients with advanced non-small-cell lung cancer before and during treatment with ICIs. EV were isolated from plasma by serial ultracentrifugation methods and circulating and EV TGF-ß expression levels were evaluated by enzyme-linked immunosorbent assay. RESULTS: Baseline high expression of TGF-ß in EVs was associated with nonresponse to ICIs as well as shorter progression-free survival and overall survival, outperforming circulating TGF-ß levels and tissue PD-L1 as a predictive biomarker. CONCLUSION: If validated, EV TGF-ß could be used to improve patient stratification, increasing the effectiveness of treatment with ICIs and potentially informing combinatory treatments with TGF-ß blockade. PLAIN LANGUAGE SUMMARY: Treatment with immune-checkpoint inhibitors (ICIs) has improved the survival of some patients with lung cancer. However, the majority of patients do not benefit from this treatment, making it essential to develop more reliable biomarkers to identify patients most likely to benefit. In this pilot study, the expression of transforming growth factor-ß (TGF-ß) in blood circulation and in extracellular vesicles was analyzed. The levels of extracellular vesicle TGF-ß before treatment were able to determine which patients would benefit from treatment with ICIs and have a longer survival with higher accuracy than circulating TGF-ß and tissue PD-L1, which is the currently used biomarker in clinical practice.
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Carcinoma de Pulmón de Células no Pequeñas , Vesículas Extracelulares , Neoplasias Pulmonares , Humanos , Carcinoma de Pulmón de Células no Pequeñas/patología , Neoplasias Pulmonares/patología , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Antígeno B7-H1 , Factor de Crecimiento Transformador beta , Proyectos Piloto , Inmunoterapia/métodos , Biomarcadores de Tumor , Vesículas Extracelulares/patología , Factores de Crecimiento Transformadores/uso terapéuticoRESUMEN
BACKGROUND: The Public Health Services at the Metropolitan Region (MR) of Chile have nine acute psychiatric beds per 100,000 inhabitants, under international recommendations. AIM: The present study will evaluate the resolution capacity of the main MR Psychiatric Emergency Room (PER), which may help assess the impact of the availability of acute beds in the MR. MATERIAL AND METHODS: A retrospective observational study of electronic patient records for all adult patients attending PER of the Psychiatric Institute "Dr. José Horwitz B." between 2017 and 2020 was analyzed. Crude and adjusted Incidence Rate Ratios were obtained for the indication of hospitalization, admissions, and those rejected due to lack of acute psychiatric beds. RESULTS: 90,464 attendances were evaluated on 41,541 patients, and hospitalization was indicated for 12.5% of them. Admissions were carried out in 59.5%, and 35.9% did not occur due to a lack of acute psychiatric beds. When comparing the adjusted Incidence Rates, only a higher hospitalization rate was observed for users from regions (IRR = 1,267; 95% CI: 1,11-1,44; p-value < 0.001) and during the first half of 2020 (IRR = 1.49; CI95%: 1.35-1.65; p-value < 0.001). CONCLUSIONS: The demand for psychiatric hospitalizations and the low availability of acute psychiatric beds in the MR probably have unsuspected consequences. The solution requires multilevel planning among all the actors involved.
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Capacidad de Camas en Hospitales , Hospitalización , Humanos , Chile/epidemiología , Estudios Retrospectivos , Masculino , Femenino , Adulto , Persona de Mediana Edad , Hospitalización/estadística & datos numéricos , Capacidad de Camas en Hospitales/estadística & datos numéricos , Adulto Joven , Adolescente , Necesidades y Demandas de Servicios de Salud/estadística & datos numéricos , Trastornos Mentales/epidemiología , Trastornos Mentales/terapia , AncianoRESUMEN
Purpose: Lack of diagnostic and prognostic biomarkers in hepatocellular carcinoma impedes stratifying patients based on their risk of developing cancer. The aim of this study was to evaluate phenotypic and genetic heterogeneity of circulating epithelial cells (CECs) based on asialoglycoprotein receptor 1 (ASGR1) and miR-122-5p expression as potential diagnostic and prognostic tools in patients with hepatocellular carcinoma (HCC) and liver cirrhosis (LC). Methods: Peripheral blood samples were extracted from LC and HCC patients at different disease stages. CECs were isolated using positive immunomagnetic selection. Genetic and phenotypic characterization was validated by double immunocytochemistry for cytokeratin (CK) and ASGR1 or by in situ hybridization with miR-122-5p and CECs were visualized by confocal microscopy. Results: The presence of CECs increased HCC risk by 2.58-fold, however, this was only significant for patients with previous LC (p = 0.028) and not for those without prior LC (p = 0.23). Furthermore, the number of CECs lacking ASGR1 expression correlated significantly with HCC incidence and absence of miR-122-5p expression (p = 0.014; r = 0.23). Finally, overall survival was significantly greater for patients at earlier cancer stages (p = 0.018), but this difference was only maintained in the group with the presence of CECs (p = 0.021) whereas progression-free survival was influenced by the absence of ASGR1 expression. Conclusion: Identification and characterization of CECs by ASGR1 and/or miR-122-5p expression may be used as a risk-stratification tool in LC patients, as it was shown to be an independent prognostic and risk-stratification marker in LC and early disease stage HCC patients.
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We describe a versatile, portable, and simple platform that includes a microfluidic electrochemical immunosensor for prostate-specific antigen (PSA) detection. It is based on the covalent immobilization of the anti-PSA monoclonal antibody on magnetic microbeads retained in the central channel of a microfluidic device. Image flow cytometry and scanning electron microscopy were used to characterize the magnetic microbeads. A direct sandwich immunoassay (with horseradish peroxidase-conjugated PSA antibody) served to quantify the cancer biomarker in serum samples. The enzymatic product was detected at -100 mV by amperometry on sputtered thin-film electrodes. Electrochemical reaction produced a current proportional to the PSA level, with a linear range from 10 pg mL-1 to 1500 pg mL-1. The sensitivity was demonstrated by a detection limit of 2 pg mL-1 and the reproducibility by a coefficient of variation of 6.16%. The clinical performance of this platform was tested in serum samples from patients with prostate cancer (PCa), observing high specificity and full correlation with gold standard determinations. In conclusion, this analytical platform is a promising tool for measuring PSA levels in patients with PCa, offering a high sensitivity and reduced variability. The small platform size and low cost of this quantitative methodology support its suitability for the fast and sensitive analysis of PSA and other circulating biomarkers in patients. Further research is warranted to verify these findings and explore its potential application at all healthcare levels.
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In addition to chronic widespread pain and depression and anxiety symptoms, patients with fibromyalgia frequently experience cognitive problems. This study investigated executive functions in fibromyalgia via a Go/No-Go task. To obtain comprehensive information about performance, traditional and ex-Gaussian parameters of reaction time (RT) variability were used, in addition to speed and accuracy indices. Ex-Gaussian parameters show an excellent fit to empirical RT distributions. Fifty-two female fibromyalgia patients and twenty-eight healthy controls participated. The task included 60 visual stimuli, which participants had to respond to (Go stimuli) or withhold the response to (No-Go stimuli). After 30 trials, the task rule changed, such that previous No-Go stimuli had to be responded to. Performance was indexed by the hit rate, false alarm rate, and mean (M) and intraindividual standard deviation (SD) of RT and the ex-Gaussian parameters mu, sigma, and tau. Mu and sigma indicate the M and SD of the Gaussian distribution; tau reflects the M and SD of the exponential function. Patients exhibited a lower hit rate, higher M RT, and higher tau than controls. Moreover, patients showed greater decrease of the hit rate after the change of task rule. In the entire sample, SD, sigma, and tau were inversely associated with the hit rate and positively associated with the false alarm rate. While the greater decline in hit rate after the change in task rule indicates deficient cognitive flexibility, the lack of any difference in false alarm rate suggests intact response inhibition. Higher M RT reflects reduced cognitive or motor speed. Increased tau in fibromyalgia indicates greater fluctuations in executive control and more frequent temporary lapses of attention. For the first time, this study demonstrated that indices of RT variability, in particular those derived from the ex-Gaussian function, may complement speed and accuracy parameters in the assessment of executive function impairments in fibromyalgia. Optimized assessment may facilitate the personalization of therapies aimed at improving the cognitive function of those with the disorder.
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Función Ejecutiva , Fibromialgia , Atención/fisiología , Cognición/fisiología , Función Ejecutiva/fisiología , Femenino , Humanos , Tiempo de Reacción/fisiologíaRESUMEN
The high prevalence of obesity and overweight in fibromyalgia (FM) may be an important factor in the well-known cognitive deficits seen in the disorder. This study analyzed the influence of body mass index (BMI) and primary clinical symptoms of FM (pain, fatigue, insomnia, anxiety, and depression) on attention, memory, and processing speed in FM. Fifty-two FM patients and thirty-two healthy participants completed cognitive tasks assessing selective, sustained, and divided attention; visuospatial and verbal memory; and information processing speed. Furthermore, they were evaluated in terms of the main clinical symptoms of the disorder. FM patients showed a marked reduction of cognitive performance in terms of selective, sustained, and divided attention; visuospatial memory; and processing speed, but no group differences were observed in verbal memory. BMI negatively affects sustained and selective attention, verbal memory, and processing speed and is the main predictor of performance in these basic cognitive domains. Our findings confirm the presence of cognitive deficits with respect to attention and visual memory, as well as slower processing speed, in FM. Moreover, the results support a role of BMI in the observed cognitive deficits. Interventions increasing physical activity and promoting cognitive stimulation could be useful for strengthening cognitive function in FM patients.
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BACKGROUND: Immune-checkpoint inhibitors (ICIs) changed the therapeutic landscape of patients with lung cancer. However, only a subset of them derived clinical benefit and evidenced the need to identify reliable predictive biomarkers. Liquid biopsy is the non-invasive and repeatable analysis of biological material in body fluids and a promising tool for cancer biomarkers discovery. In particular, there is growing evidence that extracellular vesicles (EVs) play an important role in tumor progression and in tumor-immune interactions. Thus, we evaluated whether extracellular vesicle PD-L1 expression could be used as a biomarker for prediction of durable treatment response and survival in patients with non-small cell lung cancer (NSCLC) undergoing treatment with ICIs. METHODS: Dynamic changes in EV PD-L1 were analyzed in plasma samples collected before and at 9 ± 1 weeks during treatment in a retrospective and a prospective independent cohorts of 33 and 39 patients, respectively. RESULTS: As a result, an increase in EV PD-L1 was observed in non-responders in comparison to responders and was an independent biomarker for shorter progression-free survival and overall survival. To the contrary, tissue PD-L1 expression, the commonly used biomarker, was not predictive neither for durable response nor survival. CONCLUSION: These findings indicate that EV PD-L1 dynamics could be used to stratify patients with advanced NSCLC who would experience durable benefit from ICIs.