Adenosine increases PD-L1 expression in mesenchymal stromal cells derived from cervical cancer through its interaction with A2AR/A2BR and the production of TGF-ß1.

Mesenchymal stromal cells (MSCs) together with malignant cells present in the tumor microenvironment (TME), participate in the suppression of the antitumor immune response through the production of immunosuppressive factors, such as transforming growth factor beta 1 (TGF-ß1). In previous studies, we reported that adenosine (Ado), generated by the adenosinergic activity of cervical cancer (CeCa) cells, induces the production of TGF-ß1 by interacting with A2AR/A2BR. In the present study, we provide evidence that Ado induces the production of TGF-ß1 in MSCs derived from CeCa tumors (CeCa-MSCs) by interacting with both receptors and that TGF-ß1 acts in an autocrine manner to induce the expression of programmed death ligand 1 (PD-L1) in CeCa-MSCs, resulting in an increase in their immunosuppressive capacity on activated CD8+ T lymphocytes. The addition of the antagonists ZM241385 and MRS1754, specific for A2AR and A2BR, respectively, or SB-505124, a selective TGF-ß1 receptor inhibitor, in CeCa-MSC cultures significantly inhibited the expression of PD-L1. Compared with CeCa-MSCs, MSCs derived from normal cervical tissue (NCx-MSCs), used as a control and induced with Ado to express PD-L1, showed a lower response to TGF-ß1 to increase PD-L1 expression. Those results strongly suggest the presence of a feedback mechanism among the adenosinergic pathway, the production of TGF-ß1, and the induction of PD-L1 in CeCa-MSCs to suppress the antitumor response of CD8+ T lymphocytes. The findings of this study suggest that this pathway may have clinical importance as a therapeutic target.

Adenosine Increases the Immunosuppressive Capacity of Cervical Cancer Cells by Increasing PD-L1 Expression and TGF-ß Production through Its Interaction with A2AR/A2BR.

The present study provides evidence showing that adenosine (Ado) increases the expression of programmed death ligand 1 (PD-L1) in cervical cancer (CeCa) cells by interacting with A2AR/A2BR and that TGF-ß1 acts in an autocrine manner to induce PD-L1 expression, enhancing the immunosuppressive effects of CeCa cells on activated T lymphocytes (ATLs) and CD8+ cytotoxic T lymphocytes (CTLs) specific for antigenic peptides derived from E6 and E7 proteins of HPV-16. Interestingly, the addition of the antagonists ZM241385 and MRS1754, which are specific for A2AR and A2BR, respectively, or SB-505124, which is a selective TGF-ß1 receptor inhibitor, to CeCa cell cultures significantly inhibited PD-L1 expression. In addition, supernatants from CeCa cells that were treated with Ado (CeCa-Ado Sup) increased the expression of PD-1, TGF-ß1, and IL-10 and decreased the expression of IFN-γ in ATLs. Interestingly, the addition of an anti-TGF-ß neutralizing antibody strongly reversed the effect of CeCa-Ado Sup on PD-1 expression in ATLs. These results strongly suggest the presence of a feedback mechanism that involves the adenosinergic pathway, the production of TGF-ß1, and the upregulation of PD-L1 expression in CeCa cells that suppresses the antitumor response of CTLs. The findings of this study suggest that this pathway may be clinically important and may be a therapeutic target.

In vitro activity of cefiderocol and other newly approved antimicrobials against multi-drug resistant Gram-negative pathogens recovered in intensive care units in Spain and Portugal / Actividad in vitro de cefiderocol y otros antimicrobianos recientemente aprobados frente a gramnegativos multirresistentes aislados en unidades de cuidados intensivos en España y Portugal

Introduction. The antimicrobial resistance is a significant public health threat, particularly for healthcare-associated infections caused by carbapenem-resistant Gram-negative pathogens which are increasingly reported worldwide. The aim of this study was to provide data on the in vitro antimicrobial activity of cefiderocol and that of commercially available comparator antibiotics against a defined collection of recent clinical multi-drug resistant (MDR) microorganisms, including carbapenem resistant Gram-negative bacteria collected from different regions in Spain and Portugal. Material and methods. A total of 477 clinical isolates of Enterobacterales, Pseudomonas aeruginosa, Acinetobacter baumannii and Stenotrophomonas maltophilia were prospectively (n=265) and retrospectively (n=212) included (2016-2019). Susceptibility testing was performed using standard broad microdilution and results were interpreted using CLSI-2021 and EUCAST-2021 criteria. Results. Overall, cefiderocol showed a good activity against Enterobacterales isolates, being 99.5% susceptible by CLSI and 94.5% by EUCAST criteria. It also demonstrated excellent activity against P. aeruginosa and S. maltophilia isolates, all being susceptible to this compound considering CLSI breakpoints. Regarding A. baumannii (n=64), only one isolate was resistant to cefiderocol. Conclusions. Our results are in agreement with other studies performed outside Spain and Portugal highlighting its excellent activity against MDR gram-negative bacteria. Cefiderocol is a therapeutic alternative to those available for the treatment of infections caused by these MDR bacteria. (AU)

Introducción. La resistencia a los antimicrobianos constituye una importante amenaza para la salud pública, especialmente en el caso de las infecciones relacionadas con la asistencia sanitaria causadas por patógenos gramnegativos resistentes a los carbapenémicos, las cuales están aumentando en todo el mundo. El objetivo de este estudio fue proporcionar datos sobre la actividad antimicrobiana in vitro de cefiderocol y la de antibióticos comparadores disponibles en el arsenal terapéutico frente a una colección definida de microorganismos multirresistentes (MDR) obtenidos de muestras clínicas, incluidas bacterias gramnegativas resistentes a carbapenemas procedentes de diferentes regiones de España y Portugal. Material y métodos. Se recogieron un total de 477 aislados clínicos de Enterobacterales, Pseudomonas aeruginosa, Acinetobacter baumannii y Stenotrophomonas maltophilia de forma prospectiva (n=265) y retrospectiva (n=212) (2016-2019). El estudio de sensibilidad se realizó por microdilución standard y los resultados se analizaron empleando criterios del CLSI de 2021 y de EUCAST de 2021. Resultados. En general, cefiderocol demostró una buena actividad frente a aislados de Enterobacterales, siendo 99,5% sensible según criterios del CLSI y 94,5% según los de EUCAST. Cefiderocol demostró una excelente actividad frente a aislados de P. aeruginosa y S. maltophilia, siendo todos ellos sensibles a este compuesto considerando los puntos de corte del CLSI. En relación a A. baumannii (n=64), sólo un aislado fue resistente a cefiderocol. Conclusiones. Nuestros resultados concuerdan con los de otros estudios realizados fuera de España y Portugal en los que se destaca la excelente actividad de cefiderocol frente a bacterias gramnegativas MDR. Cefiderocol constituye una alternativa terapéutica a las disponibles en el tratamiento de las infecciones causadas por estos microorganismos. (AU)

In vitro activity of ceftobiprole and dalbavancin against a collection of coagulase-negative staphylococci isolates from clinical samples with reduced susceptibility to daptomycin and/or resistant to linezolid or glycopeptides / Evaluación de la actividad in vitro de ceftobiprol y dalbavancina frente a estafilococos coagulasa negativos con sensibilidad disminuida a daptomicina y/o resistentes a linezolid o glucopéptidos aislados de muestras clínicas

Introduction:The aim was to investigate the in vitro activity of ceftobiprole and dalbavancin against a collection of coagulase-negative staphylococci (CoNS) isolates with reduced susceptibility to daptomycin or resistant to linezolid and/or glycopeptides. Methods: A total of 228 CoNS were tested using the Vitek-2 AST-626 cards (bioMérieux) and MIC of daptomycin, linezolid, vancomycin and teicoplanin were confirmed by Etest Strips (bioMérieux). Susceptibility testing for ceftobiprole and dalbavancin were performed by CLSI broth microdilution methodology. Results were interpreted according to 2021 EUCAST clinical breakpoints. Results: Ceftobiprole and dalbavancin were active against 96.0% and 93.0% of CoNS, respectively, MIC90 were 2 and 0.125mg/L. MICs of ceptobiprole were higher against S. hominis and S. haemolyticus (MIC90 4mg/L). Dalbavancin exhibited higher MICs against S. haemolyticus and CoNS with reduced susceptibility to daptomycin and resistant to teicoplanin. Conclusion: Ceftobiprole and dalbavancin demonstrated a high in vitro activity against our collection of CoNS isolates.(AU)

Introducción: El objetivo fue evaluar la actividad in vitro de dalbavancina y ceftobiprol frente a estafilococos coagulasa negativos (ECN) con sensibilidad disminuida a daptomicina y/o resistentes a linezolid o glucopéptidos. Métodos: Se testó la sensibilidad de 228 ECN con tarjetas VITEK®2 AST-626 (bioMérieux) y las CMI de daptomicina, linezolid, vancomicina y teicoplanina fueron confirmadas con tiras Etest® (bioMérieux). El ensayo de sensibilidad frente a ceftobiprol y dalbavancina se realizó mediante microdilución en caldo (metodología CLSI). Los resultados se interpretaron siguiendo los puntos de corte de EUCAST 2021. Resultados: Ceftobiprol y dalbavancina fueron activos en el 96,0 y 93% de ECN, las CMI90 fueron 2 y 0,125mg/L, respectivamente. Las CMI de ceftobiprol fueron superiores en Staphylococcus hominis y Staphylococcus haemolyticus (CMI90 4mg/L). Dalbavancina exhibió mayores CMI en S. haemolyticus y en ECN con sensibilidad disminuida a daptomicina o resistentes a teicoplanina. Conclusión: Ceftobiprol y dalbavancina han demostrado una potente actividad in vitro frente a esta colección de ECN.(AU)

Mutation in Chek2 triggers von Hippel-Lindau hemangioblastoma growth.

PURPOSE: Von Hippel-Lindau (VHL) is a rare inherited disease mainly characterized by the growth of tumours, predominantly hemangioblastomas (Hbs) in the CNS and retina, and renal carcinomas. The natural history of VHL disease is variable, differing in the age of onset and its penetrance, even among relatives. Unfortunately, sometimes VHL shows more severe than average: the onset starts in adolescence, and surgeries are required almost every year. In these cases, the factor that triggers the appearance and growth of Hbs usually remains unknown, although additional mutations are suspected. METHODS: We present the case of a VHL patient whose first surgery was at 13 years of age. Then, along his next 8 years, he has undergone 5 surgeries for resection of 10 CNS Hbs. To clarify this severe VHL condition, DNA from a CNS Hb and white blood cells (WBC) was sequenced using next-generation sequencing technology. RESULTS: Massive DNA sequencing of the WBC (germ line) revealed a pathogenic mutation in CHEK2 and the complete loss of a VHL allele (both tumour suppressors). Moreover, in the tumour sample, several mutations, in BRAF1 and PTPN11 were found. Familiar segregation studies showed that CHEK2 mutation was in the maternal lineage, while VHL was inherited by paternal lineage. CONCLUSIONS: Finally, clinical history correlated to the different genotypes in the family, concluding that the severity of these VHL manifestations are due to both, VHL-and-CHEK2 mutations. This case report aims to notice the importance of deeper genetic analyses, in inherited rare diseases, to uncover non-expected mutations.

An increase in erythromycin resistance in methicillin-susceptible Staphylococcus aureus from blood correlates with the use of macrolide/lincosamide/streptogramin antibiotics. EARS-Net Spain (2004-2020).

Objectives: To describe and analyse erythromycin resistance trends in blood isolates of Staphylococcus aureus (EARS-Net Spain, 2004-2020) and the association of these trends with the consumption of macrolide, lincosamide, and streptogramin B (MLSB) antibiotics. To assess molecular changes that could be involved in erythromycin resistance trends by whole genome analysis of representative isolates. Materials and methods: We collected antibiotic susceptibility data for all first-blood S. aureus isolates in patients from 47 Spanish hospitals according to EARS-Net criteria. MLSB antibiotic consumption was obtained from the Spanish Agency for Medicines and Medical Devices (2008-2020). We sequenced 137 representative isolates for core genome multilocus sequence typing, resistome and virulome analysis. Results: For the 36,612 invasive S. aureus isolates, methicillin resistance decreased from 26.4% in 2004 to 22.4% in 2020. Erythromycin resistance in methicillin-susceptible S. aureus (MSSA) increased from 13.6% in 2004 to 28.9% in 2020 (p < 0.001); however, it decreased from 68.7 to 61.8% (p < 0.0001) in methicillin-resistant S. aureus (MRSA). Total consumption of MLSB antibiotics increased from 2.72 defined daily doses per 1,000 inhabitants per day (DID) in 2014 to 3.24 DID in 2016. By WGS, the macrolide resistance genes detected were erm (59.8%), msrA (46%), and mphC (45.2%). The erm genes were more prevalent in MSSA (44/57, 77.2%) than in MRSA (38/80, 47.5%). Most of the erm genes identified in MSSA after 2013 differed from the predominant ermC gene (17/22, 77.3%), largely because ermT was significantly associated with MSSA after 2013 (11/29, 37.9%). All 13 ermT isolates in this study, except one, belonged to ST398 and came from 10 hospitals and six Spanish provinces. Conclusion: The significant increase in erythromycin resistance in blood MSSA correlated with the consumption of the MLSB antibiotics in Spain. These preliminary data seem support the hypothesis that the human ST398 MSSA clade with ermT-mediated resistance to erythromycin may be involved in this trend.

The CARBA-MAP study: national mapping of carbapenemases in Spain (2014-2018).

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.

CRISPR-Cas13a-Based Assay for Accurate Detection of OXA-48 and GES Carbapenemases.

Carbapenem-resistant pathogens have been recognized as a health concern as they are both difficult to treat and detect in clinical microbiology laboratories. Researchers are making great efforts to develop highly specific, sensitive, accurate, and rapid diagnostic techniques, required to prevent the spread of these microorganisms and improve the prognosis of patients. In this context, CRISPR-Cas systems are proposed as promising tools for the development of diagnostic methods due to their high specificity; the Cas13a endonuclease can discriminate single nucleotide changes and displays collateral cleavage activity against single-stranded RNA molecules when activated. This technology is usually combined with isothermal pre-amplification reactions in order to increase its sensitivity. We have developed a new LAMP-CRISPR-Cas13a-based assay for the detection of OXA-48 and GES carbapenemases in clinical samples without the need for nucleic acid purification and concentration. To evaluate the assay, we used 68 OXA-48-like-producing Klebsiella pneumoniae clinical isolates as well as 64 Enterobacter cloacae complex GES-6, 14 Pseudomonas aeruginosa GES-5, 9 Serratia marcescens GES-6, 5 P. aeruginosa GES-6, and 3 P. aeruginosa (GES-15, GES-27, and GES-40) and 1 K. pneumoniae GES-2 isolates. The assay, which takes less than 2 h and costs approximately 10 € per reaction, exhibited 100% specificity and sensitivity (99% confidence interval [CI]) for both OXA-48 and all GES carbapenemases. IMPORTANCE Carbapenems are one of the last-resort antibiotics for defense against multidrug-resistant pathogens. Multiple nucleic acid amplification methods, including multiplex PCR, multiplex loop-mediated isothermal amplification (LAMP) and multiplex RPAs, can achieve rapid, accurate, and simultaneous detection of several resistance genes to carbapenems in a single reaction. However, these assays need thermal cycling steps and specialized instruments, giving them limited application in the field. In this work, we adapted with high specificity and sensitivity values, a new LAMP CRISPR-Cas13a-based assay for the detection of OXA-48 and GES carbapenemases in clinical samples without the need for RNA extraction.

Effectiveness of fosfomycin trometamol as oral step-down therapy for bacteraemic urinary tract infections due to MDR Escherichia coli: a post hoc analysis of the FOREST randomized trial.

BACKGROUND: Fosfomycin is a potentially attractive option as step-down therapy for bacteraemic urinary tract infections (BUTI), but available data are scarce. Our objective was to compare the effectiveness and safety of fosfomycin trometamol and other oral drugs as step-down therapy in patients with BUTI due to MDR Escherichia coli (MDR-Ec). METHODS: Participants in the FOREST trial (comparing IV fosfomycin with ceftriaxone or meropenem for BUTI caused by MDR-Ec in 22 Spanish hospitals from June 2014 to December 2018) who were stepped-down to oral fosfomycin (3 g q48h) or other drugs were included. The primary endpoint was clinical and microbiological cure (CMC) 5-7 days after finalization of treatment. A multivariate analysis was performed using logistic regression to estimate the association of oral step-down with fosfomycin with CMC adjusted for confounders. RESULTS: Overall, 61 patients switched to oral fosfomycin trometamol and 47 to other drugs (cefuroxime axetil, 28; amoxicillin/clavulanic acid and trimethoprim/sulfamethoxazole, 7 each; ciprofloxacin, 5) were included. CMC was reached by 48/61 patients (78.7%) treated with fosfomycin trometamol and 38/47 (80.9%) with other drugs (difference, -2.2; 95% CI: -17.5 to 13.1; P = 0.38). Subgroup analyses provided similar results. Relapses occurred in 9/61 (15.0%) and 2/47 (4.3%) of patients, respectively (P = 0.03). The adjusted OR for CMC was 1.11 (95% CI: 0.42-3.29, P = 0.75). No relevant differences in adverse events were seen. CONCLUSIONS: Fosfomycin trometamol might be a reasonable option as step-down therapy in patients with BUTI due to MDR-Ec but the higher rate of relapses would need further assessment.

Effect of ultra-processed food intake on metabolic syndrome components and body fat in children and adolescents: A systematic review based on cohort studies.

OBJECTIVES: The aim of this study was to thoroughly review the scientific literature related to cohort studies that evaluated the association between the intake of ultra-processed foods, according to the NOVA classification, and the increase in the components of metabolic syndrome and body fat in children and adolescents. METHODS: We consulted the PubMed, Scielo, Lilacs, and ScienceDirect databases and selected cohort studies that met the main objective of this review and included the age group of interest. We used an adaptation of the Newcastle-Ottawa scale to evaluate cohort studies. RESULTS: Of 383 articles identified, 367 were excluded after reading the title, abstract, and methodology. Only nine met the selection criteria defined for this review. Of the nine articles, two reported a positive association between high consumption of ultra-processed foods and total cholesterol levels; one reported a positive association with low-density lipoprotein cholesterol, one with triacylglycerols, one with diastolic blood pressure, three with body mass index, two with waist circumference, and two with body fat. CONCLUSIONS: Seven of nine studies found at least one association with components of metabolic syndrome. This highlights the importance of early intervention to prevent non-communicable diseases in the future.

Short-Term Ambient Air Ozone Exposure and Components of Metabolic Syndrome in a Cohort of Mexican Obese Adolescents.

Ambient air pollution is a major global public health concern; little evidence exists about the effects of short-term exposure to ozone on components of metabolic syndrome in young obese adolescents. The inhalation of air pollutants, such as ozone, can participate in the development of oxidative stress, systemic inflammation, insulin resistance, endothelium dysfunction, and epigenetic modification. Metabolic alterations in blood in components of metabolic syndrome (MS) and short-term ambient air ozone exposure were determined and evaluated longitudinally in a cohort of 372 adolescents aged between 9 to 19 years old. We used longitudinal mixed-effects models to evaluate the association between ozone exposure and the risk of components of metabolic syndrome and its parameters separately, adjusted using important variables. We observed statistically significant associations between exposure to ozone in tertiles in different lag days and the parameters associated with MS, especially for triglycerides (20.20 mg/dL, 95% CI: 9.5, 30.9), HDL cholesterol (-2.56 mg/dL (95% CI: -5.06, -0.05), and systolic blood pressure (1.10 mmHg, 95% CI: 0.08, 2.2). This study supports the hypothesis that short-term ambient air exposure to ozone may increase the risk of some components of MS such as triglycerides, cholesterol, and blood pressure in the obese adolescent population.

Outbreak of Arcobacter butzleri? An emerging enteropathogen.

BACKGROUND: Arcobacter butzleri is a gram-negative rod, with microaerobic growth at an optimal temperature of 37°C. It was reported to be the fourth most common Campylobacter-like organism isolated from patients with diarrhoea. OBJECTIVE: Characterise a potential outbreak of A. butzleri detected in a short period of time in the University Hospital Marqués de Valdecilla. METHODS: Eight strains of A. butzleri were detected in our hospital in only two months. Isolates were identified by MALDI-TOF MS system and 16S rDNA sequencing. Enterobacterial repetitive intergenic consensus-PCR (ERIC-PCR) and Pulsed Field Gel Electrophoresis (PFGE) were carried out to assess clonal relationship. Gradient strips (Etest) were used to determine susceptibility by agar diffusion. RESULTS: ERIC-PCR and PFGE confirmed the lack of clonal relationship between strains. Erythromycin or ciprofloxacin might be appropriate for antibiotic treatment of infections. CONCLUSIONS: A. butzleri is an emerging pathogen with increasing incidence, and may be underestimated.

Outbreak of Arcobacter butzleri? An emerging enteropathogen / Brote de Arcobacter butzleri? Un enteropatógeno emergente

Background: Arcobacter butzleri is a gram-negative rod, with microaerobic growth at an optimal temperature of 37°C. It was reported to be the fourth most common Campylobacter-like organism isolated from patients with diarrhoea. Objective: Characterise a potential outbreak of A. butzleri detected in a short period of time in the University Hospital Marqués de Valdecilla. Methods: Eight strains of A. butzleri were detected in our hospital in only two months. Isolates were identified by MALDI-TOF MS system and 16S rDNA sequencing. Enterobacterial repetitive intergenic consensus-PCR (ERIC-PCR) and Pulsed Field Gel Electrophoresis (PFGE) were carried out to assess clonal relationship. Gradient strips (Etest) were used to determine susceptibility by agar diffusion. Results: ERIC-PCR and PFGE confirmed the lack of clonal relationship between strains. Erythromycin or ciprofloxacin might be appropriate for antibiotic treatment of infections. Conclusions: A. butzleri is an emerging pathogen with increasing incidence, and may be underestimated.(AU)

Antecedentes: Arcobacter butzleri es un bacilo gramnegativo, con crecimiento microaerófilo a una temperatura óptima de 37°C. Ha sido descrito como el cuarto organismo asociado a Campylobacter más frecuentemente aislado de pacientes con diarrea. Objetivo: Caracterizar un potencial brote de A. butzleri detectado en el Hospital Universitario Marqués de Valdecilla. Métodos: Se detectaron 8 cepas de A. butzleri en nuestro hospital en solo 2 meses. Los aislamientos fueron identificados con MALDI-TOF MS y secuenciación del ARNr 16S. Se llevó a cabo la PCR basada en secuencia de consenso intergénica repetitiva de enterobacterias(ERIC-PCR) y electroforesis en campo pulsado (PFGE) para asegurar la relación clonal. Para determinar la sensibilidad se usaron tiras de gradiente (Etest®) por difusión en agar. Resultados: ERIC-PCR y PFGE confirmaron la falta de relación clonal entre las cepas. Eritromicina o ciprofloxacino podrían ser apropiados para el tratamiento antibiótico de estas infecciones. Conclusiones: A. butzleri es un patógeno emergente con un aumento en la incidencia, y podría estar subestimado.(AU)

Ileal signet-ring cell carcinoma with brain metastases: A case report.

Background: Signet-ring cell carcinoma (SRCC) is a rare subtype of adenocarcinoma that frequently originates in the stomach. Uncommonly, this tumor can lead to brain metastases; an event rarely reported in the literature. Case Description: A 76-year-old man with a history of cognitive impairment was diagnosed with two brain space-occupying lesions. A whole-body 18F-FDG PET/computed tomography scan revealed a hypermetabolic lesion in a segment of the ileum corresponding to mural thickening and an ulcerated lesion detected on colonoscopy. A brain biopsy, using an immunohistochemistry protocol, showed signet-ring cells with a pattern that suggested an intestinal origin. The diagnosis of SRCC brain metastases with an ileal origin was made, and a treatment protocol was designed. However, the patient rapidly deteriorated, and passed away shortly afterward. Conclusion: To the best of our knowledge, this is the first case report of an ileal SRCC with brain metastases.

Inhibition of CD73 expression or A2AR blockade reduces MRP1 expression and increases the sensitivity of cervical cancer cells to cisplatin.

Recently, a link between the biological activity of CD73 in solid tumors and multidrug resistance protein (MRP) has been proposed. Cisplatin (CP) is the most widely used anticancer agent to treat advanced and recurrent cervical cancer (CC). However, multidrug resistance protein-1 (MRP1) is overexpressed in approximately 85% of these tumors and has been strongly associated with cisplatin resistance (CPR). In this study, we examine the involvement of CD73 and the interaction of adenosine (ADO) with its receptors (ARs) in MRP1 expression in CC cells. We found that ADO positively modulates MRP1 expression in CC cells in a dose-dependent manner. The inhibition of CD73 expression with a CD73-targeted siRNA and A2AR blockade with the selective antagonist ZM241385 significantly decreased MRP1 expression and the extrusive capacity of CC cells, making them significantly more sensitive to CP treatment than cancer cells treated with MK-751, a specific MRP1 inhibitor. These results suggest CD73 inhibition or blocking ADO signaling through A2AR could be strategies to reverse CPR in patients with advanced or recurrent CC, which is characterized by very low response rates to CP (10%-20%).

Oportunistic diagnosis based on age and hepatitis C virus clearance: an essential step to improve the overall health of the liver.

Back in January 2022, an EASL-Lancet Commission on the impact of liver disorders in the European region commissioned by the WHO demonstrated that this condition is, actually, the second leading cause of loss of labor years in Europe after ischemic heart disease (1). This is a very relevant piece of information since this is something that is going to impact the new generations of Europeans unless a significant change is made in public health policies. Despite the advances made over the last few years in hepatitis C virus clearance-understood as a significant reduction of morbidity and mortality associated with Hepatitis B and C viruses-there are still challenges ahead to improve liver health due to the high use of alcohol, and the inseparable triad obesity / diabetes mellitus / metabolic associated fatty liver disease. Also, access to healthcare for several population groups at risk of presenting higher rates of liver disease has become a problem.

Diagnóstico oportunista basado en la edad y eliminación de la hepatitis C: un paso imprescindible para mejorar la salud hepática global / Opportunistic diagnosis based on age and elimination of hepatitis C: an essential step to improve global liver health

En enero de este 2022 una Comisión de EASL-Lancet sobre el impacto de las enfermedades hepáticas en la región europea de la OMS mostró que esta patología es actualmente la segunda causa de pérdida de años de vida laboral en Europa, después de la cardiopatía isquémica. Esto es un dato muy relevante ya que va a impactar en las nuevas generaciones europeas si no existe un cambio importante en las políticas de salud pública. A pesar de los avances de los últimos años en la eliminación de las hepatitis virales entendidas como una disminución importante en la morbimortalidad de la hepatitis B y C, aún quedan retos para mejorar la salud hepática debido al elevado consumo de alcohol, la inseparable tripleta de obesidad / diabetes mellitus / esteatosis hepática metabólica y las dificultades en el acceso a la salud de amplios colectivos de nuestra población, que característicamente están en riesgo de presentar tasas más elevadas de enfermedad hepática (AU)

[Family typologies for dengue prevention in Colombia]. / Tipologías familiares para la prevención del dengue en Colombia.

The aim of this study was to analyze the relationship between sociodemographic characteristics and risk factors of the context to establish family typologies based on the control and prevention of dengue in the Department of Córdoba, Colombia, through a cross-sectional analytical study carried out during the year 2021 with 328 families. For this purpose, the proportional random stratified sampling technique was used, with a 90% confidence level and 7% error. Associations between pairs of variables were measured using the chi-square test at a significance level of 5%. For the joint measurement of the associations between variables, a multiple correspondence analysis was used. The grouping of families was done using a conglomerate analysis (cluster) and Ward's hierarchical agglomerative method. Four types of families were determined, highlighting two among them. The first, with 163 households, mainly from Montería, groups families with better educational levels, higher income, greater participation in preventive programs, better access to public services and less presence of stagnant water; the second group is composed by families with incomplete elementary school, precarious access to drinking water and/or sewage services, lower economic income and higher prevalence of the triggers for the spread of the vector. The analysis of the link family/dengue prevention justifies further studies on the subject for the implementation of comprehensive contextualized strategies that address the particularities of the territory and the variability of sociodemographic characteristics.

Se buscó analizar la relación entre las características sociodemográficas y los factores de riesgo del contexto para establecer tipologías familiares en función del control y prevención del dengue en el Departamento de Córdoba, Colombia, a través de un estudio analítico transversal realizado durante el año 2021 con 328 familias. Para el efecto se utilizó la técnica del muestreo estratificado aleatorio proporcional, con un nivel de 90% de confianza y 7% de error. La medición de las asociaciones entre pares de variables se hizo mediante la prueba chi-cuadrado a un nivel de significancia del 5%. Para la medición en conjunto de las asociaciones entre variables se utilizó un análisis de correspondencias múltiple. La agrupación de las familias se hizo mediante un análisis de conglomerados (clúster) y el método aglomerativo jerárquico de Ward. Se determinaron cuatro tipologías de familias, resaltándose dos entre ellas. El primero, de 163 hogares, principalmente de Montería, agrupa familias con mejores niveles educativos, mayores ingresos, mayor participación en programas preventivos, mejor acceso a servicios públicos y menor presencia de aguas estancadas; el segundo grupo, lo integran familias con primaria incompleta, precariedad en el acceso al servicio de agua potable y/o alcantarillado, menores ingresos económicos y mayor prevalencia de los detonantes para la propagación del vector. El análisis del vínculo familia/prevención del dengue amerita la profundización de estudios sobre el tema para la implementación de estrategias integrales contextualizadas que atiendan las particularidades del territorio y la variabilidad de las características sociodemográficas.

O objetivo do artigo foi analisar a relação entre características sociodemográficas e fatores de risco do contexto para estabelecer tipologias familiares baseadas no controle e prevenção da dengue no Departamento de Córdoba, Colômbia, por meio de um estudo analítico transversal realizado durante o ano de 2021 com 328 famílias. Para tanto, foi utilizada a técnica de amostragem estratificada aleatória proporcional, com nível de 90% de confiança e erro de 7%. As associações entre os pares de variáveis ​​foram medidas pelo teste qui-quadrado a um nível de significância de 5%. Para a mensuração conjunta das associações entre as variáveis, foi utilizada a análise de correspondência múltipla. O agrupamento das famílias foi feito por meio de análise de conglomerado (cluster) e método aglomerativo hierárquico de Ward. Foram determinados quatro tipos de famílias, destacando-se dois. O primeiro, de 163 domicílios, principalmente de Montería, agrupa famílias com melhor nível educacional, maior renda, maior participação em programas preventivos, melhor acesso a serviços públicos e menor presença de água estagnada; o segundo grupo é formado por famílias com Ensino Fundamental incompleto, acesso precário a serviços de água potável e/ou esgotamento sanitário, menor renda econômica e maior prevalência dos desencadeantes da disseminação do vetor. A análise do vínculo família/prevenção da dengue justifica estudos sobre o tema para a implementação de estratégias abrangentes e contextualizadas que contemplem as particularidades do território e a variabilidade das características sociodemográficas.