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PD-1/PD-L1 axis: implications in immune regulation, cancer progression, and translational applications.
No full text20.500.12530/87908The PD-1/PD-L1 axis is a complex signaling pathway that has an important role in the immune system cells. Programmed cell death protein 1 (PD-1) acts as an immune checkpoint on the T lymphocytes, B lymphocytes, natural killer (NK), macrophages, dendritic cells (DCs), monocytes, and myeloid cells. Its ligand, the programmed cell death 1 ligand (PD-L1), is expressed in the surface of the antigen-presenting cells (APCs). The binding of both promotes the downregulation of the T cell response to ensure the activation to prevent the onset of chronic immune inflammation. This axis in the tumor microenvironment (TME) performs a crucial role in the tumor progression and the escape of the tumor by neutralizing the immune system, the engagement of PD-L1 with PD-1 in the T cell causes dysfunctions, neutralization, and exhaustion, providing the tumor mass production. This review will provide a comprehensive overview of the functions of the PD-1/PD-L1 system in immune function, cancer, and the potential therapeutic implications of the PD-1/PD-L1 pathway for cancer management
The RICA-2 registry: design and baseline characteristics of the first 1,000 patients.
No full text20.500.12530/87908Heart failure (HF) is a syndrome of epidemic proportions and one of the main reasons for hospital admission. Patient registries provide real-world clinical practice information which is complementary to clinical trials. RICA-2 is a registry of the Spanish Society of Internal Medicine. Its main goal is to know the clinical and epidemiological characteristics and prognostic factors of patients with HF treated in Internal Medicine Departments. The objective of this study is to present the design of the RICA-2, the baseline characteristics of the first 1000 patients included and their comparison with those of the historical cohort of the RICA registry. Observational, multicentre and prospective study of patients with HF with the following inclusion criteria: age equal to or greater than 18 years old, diagnosis of HF according to the European Guidelines, indistinct inclusion in decompensation or stable phase, of patients with de novo HF or chronic HF, regardless of left ventricular ejection fraction, aetiology and comorbidities. RICA-2 patients have advanced age (83 years old) and 51% are women. The comorbidity burden is higher than in the RICA registry (5 points in the Charlson comorbidity index), with predominating chronic decompensated HF (74%), hypertensive aetiology (39%) and preserved ejection fraction (52%). Most patients are pre-frail or vulnerable and are at risk of malnutrition. The RICA-2 represents a contemporary cohort of patients that will provide us with clinical, epidemiological and prognostic information on patients with acute and chronic HF treated in Internal Medicine
Short-sighted evolution of virulence for invasive gut microbes: From hypothesis to tests.
No full text20.500.12530/87854Why microbes harm their hosts is a fundamental question in evolutionary biology with broad relevance to our understanding of infectious diseases. Several hypotheses have been proposed to explain this "evolution of virulence." In this perspective, we reexamine one of these hypotheses in the specific context of the human gut microbiome, namely short-sighted evolution. According to the short-sighted evolution hypothesis, virulence is a product of niche expansion within a colonized host, whereby variants of commensal microbes establish populations in tissues and sites where the infection causes morbidity or mortality. This evolution is short-sighted in that the evolved variants that infect those tissues and sites are not transmitted to other hosts. The specific hypothesis that we propose is that some bacteria responsible for invasive infections and disease are the products of the short-sighted evolution of commensal bacteria residing in the gut microbiota. We present observations in support of this hypothesis and discuss the challenges inherent in assessing its general application to infections and diseases associated with specific members of the gut microbiota. We then describe how this hypothesis can be tested using genomic data and animal model experiments and outline how such studies will serve to provide fundamental information about both the evolution and genetic basis of virulence, and the bacteria of intensively studied yet poorly understood habitats including the gut microbiomes of humans and other mammals
Biological relapse in multiple myeloma: Outcome and treatment strategies in a Spanish real-world setting.
No full textRecommendations regarding the best time to start treatment in patients with relapsed/refractory multiple myeloma (RRMM) after biological relapse/progression (BR) are unclear. This observational, prospective, multicenter registry aimed to evaluate the impact on time to progression (TTP) of treatment initiation at BR versus at symptomatic clinical relapse (ClinR) based on the Spanish routine practice in adult patients with RRMM. Patients had two or less previous treatment lines and at least one previous partial response. Baseline characteristics and treatment outcomes were recorded, and survival was analyzed. Of 225 patients, 110 were treated at BR (TxBR group) and 115 at ClinR (TxClinR group) according to the investigators' criteria. The proportion of patients with higher ECOG, previous noncomplete remission (CR), and second relapse were significantly higher in the TxBR group compared to the TxClinR group. TheTxClinR group showed improved outcomes, including TTP, compared to the TxBR group. Progression-free survival increased in the TxClinR group (56.2 months) compared to the TxBR group (32.5 months) (p = 0.0137), and median overall survival also increased (p = 0.0897). Median TTP was significantly longer in patients relapsing from a CR (50.4 months) and in their first relapse (38.7 months) compared to those relapsing from a non-CR response (32.9 months) and in their second relapse (25.2 months). Physicians seemed to start treatment earlier in RRMM patients with poor prognosis features. Previous responses to anti-MM treatment and the number of prior treatment lines were identified as prognosis factors, whereby relapse from CR and first relapse were associated with a longer time to progression
Impact of a pulmonary embolism response team (PERT) in the prognosis of patients with acute symptomatic pulmonary embolism.
No full text20.500.12530/87854The effect of a pulmonary embolism response team (PERT) in the short-term prognosis of patients with acute symptomatic pulmonary embolism (PE) lacks clarity. We therefore aimed at evaluating the effect of a PERT team on short-term mortality among patients with acute PE. We retrospectively reviewed consecutive patients with acute symptomatic PE enrolled in a single-center registry between 2007 and 2022. We used propensity score matching to compare treatment effects for patients with similar predicted probabilities of receiving management by the PERT team. The primary outcome was all-cause mortality within 30 days following the diagnosis of PE. The secondary outcome was 30-day PE-related mortality. Of the 2,902 eligible patients who had acute symptomatic PE, 223 (7.7%; 95% confidence interval [CI], 6.7%-8.7%) were managed by the PERT team. Two hundred and seven patients who were treated by the PERT were matched with 207 patients who were not. Matched pairs did not show a statistically significant lower all-cause (odds ratio [OR], 1.09; 95% CI, 0.63-1.89) or PE-related death (OR, 1.30; 95% CI, 0.47-3.62) for PERT management compared with no PERT management through 30 days after diagnosis of PE. Our results suggest that multidisciplinary care of patients with acute symptomatic PE by a PERT team is not associated with a significant reduction in short-term all-cause or PE-related mortality
Diagnostic Accuracy of Neurocognitive and Executive Functions to Discriminate Women With and Without Fibromyalgia Syndrome: A Secondary Analysis.
No full textObjective: The aim of the current study was to determine the capability of neurocognitive variables and executive functions to differentiate women with and without fibromyalgia syndrome (FMS). Methods: A secondary diagnostic accuracy analysis was conducted. A battery of neurocognitive and executive function tests (the D2 Attention test, the Rey-Osterrieth Complex Figure for visual perception, "Digits D/R/I" tests of the WAIS-IV battery for working memory, the 5-Digit test for mental inhibition, the Symbol Search for processing speed, and the Zoo Test for planning/decision-making) were collected in 129 women with FMS and 111 without FMS. The area under the receiver operating characteristic (ROC) curve, optimal cut-off point, sensitivity, specificity, and positive and negative likelihood ratios (LR) for each variable were calculated. Results: Between-group differences were identified in ROCF_Copy (p = 0.043), ROCF_Recall (p = 0.004), d2_TR (p = 0.019), d2_TA (p = 0.007), d2_TOT (p = 0.005), d2_CON (p = 0.004), d2_C (p = 0.042), Symbol Search (p = 0.008), Decoding _FDT (p = 0.001), Retrieving_FDT (p = 0.001), and Inhibiting_FDT (p = 0.024). The result showed that FDT-based outcomes (Retrieving_FDT: ROC 0.739, sensitivity 85.3%, specificity 48.6%; Decoding_FDT: ROC 0.724, sensitivity 50.4%, specificity 16.2%; Inhibiting_FDT: ROC 0.708, sensitivity 56.6%, specificity 22.5%) were the variables able to differentiate between women with and without FMS. Conclusions: Although women with FMS exhibited deficits in attention, long-term visual memory, processing speed, and mental inhibition when compared with women without FMS, only mental inhibition scores showed moderate diagnostic accuracy to discriminate between women with and without FMS. Future studies investigating these results in clinical settings are needed to identify the clinical relevance of these findings
Multiplex spatial analysis reveals increased CD137 expression and m-MDSC neighboring tumor cells in refractory classical Hodgkin Lymphoma.
No full text20.500.12530/87854The Hodgkin and Reed - Sternberg (HRS) cells in classical Hodgkin Lymphoma (cHL) actively modify the immune tumor microenvironment (TME) attracting immunosuppressive cells and expressing inhibitory molecules. A high frequency of myeloid cells in the TME is correlated with an unfavorable prognosis, but more specific and rare cell populations lack precise markers. Myeloid-derived suppressor cells (MDSCs) have been identified in the peripheral blood of cHL patients, where they appear to be correlated with disease aggressiveness. TNFRSF9 (CD137) is a T cell co-stimulator expressed by monocytic and dendritic cells. Its expression has also been described in HRS cells, where it is thought to play a role in reducing antitumor responses. Here, we perform qualitative and quantitative analyses of lymphocytic and MDSC subtypes and determine the CD137 cell distribution in cHL primary tumors using multiplex immunofluorescence and automated multispectral imaging. The results were correlated with patients' clinical features. Cells were stained with specific panels of immune checkpoint markers (PD-1, PD-L1, CD137), tumor-infiltrating T lymphocytes (CD3, PD-1), and monocytic cells/MDSCs (CD68, CD14, CD33, Arg-1, CD11b). This approach allowed us to identify distinct phenotypes and to analyze spatial interactions between immune subpopulations and tumor cells. The results confirm CD137 expression by T, monocytic and HRS cells. In addition, the expression of CD137, T exhausted cells, and monocytic MDSCs (m-MDSCs) in the vicinity of malignant HRS cells were associated with a worse prognosis. Our findings reveal new elements of the TME that mediate immune escape, and confirm CD137 as a candidate target for immunotherapy in cHL
Proceedings of the 5th Meeting of Translational Hepatology, organized by the Spanish Association for the Study of the Liver (AEEH).
No full text20.500.12530/87854This is the summary report of the 5th Translational Hepatology Meeting, endorsed by the Spanish Association for the Study of the Liver (AEEH) and held in Seville, Spain, in October 2023. The meeting aimed to provide an update on the latest advances in the field of basic and translational hepatology, covering different molecular, cellular, and pathophysiological aspects of the most relevant clinical challenges in liver pathologies. This includes the identification of novel biomarkers and diagnostic tools, the understanding of the relevance of immune response and inflammation in liver diseases, the characterization of current medical approaches to reverse liver diseases, the incorporation of novel molecular insights through omics techniques, or the characterization of the impact of toxic and metabolic insults, as well as other organ crosstalk, in liver pathophysiology
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No full textImpact of Frailty on Heart Failure Prognosis: Is Sex Relevant?
No full textHeart failure (HF) is one of the most frequent causes of hospital admission in elderly patients, especially in women, who present a high prevalence of geriatric syndromes like frailty. Studies have suggested that frailty and its impact may also differ between males and females. Understanding how frailty may differently affect HF patients depending on sex is therefore imperative for providing personalized care. The aim of this review is to summarize the role of sex in the prognostic impact of frailty in HF patients. Numerous studies have identified frailty as a significant predictor of all-cause mortality and hospital readmissions. A recent study of elderly HF out-patients demonstrated that while women had a higher prevalence of frailty, it was an independent predictor of mortality and readmission only in men. Moreover, another study revealed that physical frailty was associated with time to first clinical event among men but not among women. These results raise the question about why frailty affects differently HF prognosis in men and women. Women with HF present a higher prevalence of frailty, especially when it is considered as physical decline. Nevertheless, frailty affects differently HF prognosis in men and women. Women with HF present lower mortality than men and frailty is related with prognosis only in men. The different severity of HF between men and women and other hormonal, psychosocial, and clinical factors might be involved in this fact