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Background: Systemic inflammation plays a central role in atrial fibrillation (AF). The neutrophil-to-lymphocyte ratio (NLR) is a simple hematological index that has been shown to be associated with prognosis in different pathologies., Hypothesis: The NLR is associated with an increased risk of adverse events in patients with AF., Methods: We included a prospective cohort of AF patients who started vitamin K antagonists (VKAs) therapy between July 2016 and June 2018. NLR was assessed at baseline and classified into three categories: low (< 3), moderate (3-5), and high (> 5). During a 2-year follow-up period, all cardiovascular deaths, all-cause deaths, and net clinical outcomes (NCO; either ischemic stroke/transient ischemic attack, major bleeding or all-cause death), were recorded., Results: A total of 1050 patients were included (51.4% women; median age 77 years). NLR was available in 936 patients: 507 (54.2%) had low NLR (< 3), 239 (25.5%) had moderate NLR (3-5), and 190 (20.3%) had high NLR (> 5). The primary endpoint was significantly increased in the high NLR category (p = 0.002 for cardiovascular death; p < 0.001 for all-cause mortality, and p < 0.001 for NCO), with higher IRRs (all p < 0.001). Multivariate Cox regression analyses showed that high NLR was independently associated with an increased risk of cardiovascular death (aHR: 2.02; 95% CI: 1.04-3.92), all-cause mortality (aHR: 2.51; 95% CI: 1.58-3.97), and NCO (aHR: 1.99; 95% CI: 1.37-2.87), compared to low NLR., Conclusions: In this prospective AF cohort receiving VKAs, elevated NLR was significantly associated with an increased risk of adverse clinical outcomes. NLR has independent prognostic value beyond other classical risk factors., (© 2025 The Author(s). Clinical Cardiology published by Wiley Periodicals LLC.)

Background: Atrial fibrillation (AF) patients often present with a higher prevalence of comorbidities, frailty, and malnutrition. We investigated if multimorbidity, frailty and malnutrition were associated with clinical outcomes in patients with AF starting vitamin K antagonist (VKA) therapy., Methods: Prospective observational cohort study including AF outpatients starting VKAs from July 2016 to June 2018. Multimorbidity was assessed by the number of comorbidities, frailty was evaluated using the Clinical Frailty Scale (CFS), and nutritional status was appraised using the Controlling Nutritional Status (CONUT). During 2-years of follow-up, ischemic strokes/transient ischemic attacks (TIA), major bleeds, and all-cause deaths, were recorded., Results: 1050 AF patients (51.4% female; median age 77 years, IQR 70-83) were included. Of these, 912 (86.9%) had multimorbidity (≥2 comorbidities additional to AF), 186 (17.7%) exhibited any frailty degree (CFS ≥ 5), and 76 (7.2%) had moderate-to-severe malnutrition (CONUT ≥ 5). The crude number of comorbidities and the CFS were significantly associated with major bleeds, whereas the CFS and the CONUT score were related to all-cause mortality. After adjustment, any frailty degree was associated with higher risks of major bleeding (aHR 3.04, 95% CI 1.67-5.52) and death (aHR 2.04, 95% CI 1.39-3.01). Moderate-to-severe malnutrition increased risk for ischemic stroke/TIA (aHR 2.25, 95% CI 1.11-4.56) and all-cause mortality (aHR 3.21, 95% CI 2.14-4.83)., Conclusions: In this real-world prospective cohort of AF taking VKAs, most patients had multiple comorbidities, frailty and malnutrition. Frailty and malnutrition were important risk factors for bleeding, stroke, and mortality in these patients., (Copyright © 2024 The Author(s). Published by Elsevier Masson SAS.. All rights reserved.)

Introduction and Objectives: Stroke and bleeding risks in atrial fibrillation (AF) are often assessed at baseline to predict outcomes years later. We investigated whether dynamic changes in CHA 2 DS 2 -VASc and HAS-BLED scores over time modify risk prediction., Methods: We included patients with AF who were stable while taking vitamin K antagonists. During a 6-year follow-up, all ischemic strokes/transient ischemic attacks (TIAs) and major bleeding events were recorded. CHA 2 DS 2 -VASc and HAS-BLED were recalculated every 2-years and tested for clinical outcomes at 2-year periods., Results: We included 1361 patients (mean CHA 2 DS 2 -VASc and HAS-BLED 4.0±1.7 and 2.9±1.2). During the follow-up, 156 (11.5%) patients had an ischemic stroke/TIA and 269 (19.8%) had a major bleeding event. Compared with the baseline CHA 2 DS 2 -VASc, the CHA 2 DS 2 -VASc recalculated at 2 years had higher predictive ability for ischemic stroke/TIA during the period from 2 to 4 years. Integrated discrimination improvement (IDI) and net reclassification improvement (NRI) showed improvements in sensitivity and better reclassification. The CHA 2 DS 2 -VASc recalculated at 4 years had better predictive performance than the baseline CHA 2 DS 2 -VASc during the period from 4 to 6 years, with an improvement in IDI and an enhancement of the reclassification. The recalculated HAS-BLED at 2-years had higher predictive ability than the baseline score for major bleeding during the period from 2 to 4 years, with significant improvements in sensitivity and reclassification. A slight enhancement in sensitivity was observed with the HAS-BLED score recalculated at 4 years compared with the baseline score., Conclusions: In AF patients, stroke and bleeding risks are dynamic and change over time. The CHA 2 DS 2 -VASc and HAS-BLED scores should be regularly reassessed, particularly for accurate stroke risk prediction., (Copyright © 2024 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.)

Background: Some clinical characteristics and comorbidities in atrial fibrillation (AF) patients are exclusion criteria in randomized clinical trials (RCTs) investigating oral anticoagulants (OAC). However, these conditions are present also in everyday clinical practice patients. We compared the risk of adverse clinical outcomes between patients with and without RCT exclusion criteria., Methods: The Murcia AF Project II was an observational cohort study including AF outpatients starting vitamin K antagonists (VKAs) from July 2016 to June 2018. For the selection of the exclusion criteria, the four pivotal RCTs of direct-acting OAC (DOACs) were used as reference. During 2 years, all ischemic strokes/transient ischemic attacks, major adverse cardiovascular events (MACEs), major bleeds, and all-cause deaths were recorded., Results: 1050 patients (51.5% female, median age 77 years) were included, of whom 368 (35%) met at least one exclusion criterion for RCTs. During follow-up, the incidence rate ratios for major bleeding, MACE and all-cause mortality were higher among patients with exclusion criteria (all p < 0.001). Patients fulfilling at least one exclusion criterion had increased risks of major bleeding (aHR 1.48; 95% CI 1.22-1.81; p < 0.001), MACE (aHR 1.51, 95% CI 1.10-2.09, p = 0.012), and mortality (aHR 3.22, 95% CI 2.32-4.48, p < 0.001), as well as a lower event-free survival (all log-rank p < 0.001)., Conclusions: In this AF cohort taking VKAs, more than one-third had at least one RCT exclusion criteria, which translates into higher risk of major bleeding, MACE, and death. These observations should be considered when translating RCTs results to AF patients for a proper and a more patient-centered management., (© 2024. The Author(s).)

Introduction: With the increasing prevalence of atrial fibrillation (AF), it entails expanding oral anticoagulants (OACs) use, carrying a higher risk of associated hemorrhagic events, including intracranial hemorrhage (ICH). Despite advances in OACs development with a better safety profile and reversal agent for these anticoagulants, there is still no consensus on the optimal management of patients with OACs-associated ICH., Areas Covered: In this review, the authors have carried out an exhaustive search on the advances in recent years. The authors provide an update on the management of ICH in anticoagulated patients, as well as an update on the latest evidence on anticoagulation resumption, recent therapeutic strategies, and investigational drugs that could play a role in the future., Expert Opinion: Following an ICH event in an anticoagulated patient, a comprehensive clinical evaluation is imperative. Anticoagulation should be promptly withdrawn and reversed. Once the patient is stabilized, a reintroduction of anticoagulation should be considered, typically within a timeframe of 4-8 weeks, if feasible. If re-anticoagulation is not possible, alternative options such as Left Atrial Appendage Occlusion are available.

Introduction: Scarce real-life data exists for COVID-19 management in hematologic disease (HD) patients in the Omicron era., Purpose: To assess the current clinical management and outcome of SARS-CoV-2 infection diagnosed, identify the risk factors for severe outcomes according to the HD characteristics and cell therapy procedures in a real-world setting., Methods: A retrospective observational registry led by the Spanish Transplant Group (GETH-TC) with 692 consecutive patients with HD from December 2021 to May 2023 was analyzed., Results: Nearly one-third of patients (31%) remained untreated and presented low COVID-19-related mortality (0.9%). Nirmatrelvir/ritonavir was used mainly in mild COVID-19 cases in the outpatient setting (32%) with a low mortality (1%), while treatment with remdesivir was preferentially administered in moderate-to-severe SARS-CoV-2 infection cases during hospitalization (35%) with a mortality rate of 8.6%. The hospital admission rate was 23%, while 18% developed pneumonia. COVID-19-related mortality in admitted patients was 14%. Older age, autologous hematopoietic stem cell transplantation (SCT), chimeric antigen receptor T-cell therapy, corticosteroids and incomplete vaccination were factors independently associated with COVID-19 severity and significantly related with higher rates of hospital admission and pneumonia. Incomplete vaccination status, treatment with prior anti-CD20 monoclonal antibodies, and comorbid cardiomyopathy were identified as independent risk factors for COVID-19 mortality., Conclusions: The results support that, albeit to a lower extent, COVID-19 in the Omicron era remains a significant problem in HD patients. Complete vaccination (3 doses) should be prioritized in these immunocompromised patients. The identified risk factors may help to improve COVID-19 management to decrease the rate of severe disease, ICU admissions and mortality., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Piñana, Vazquez, Heras, Aiello, López-Corral, Arroyo, Soler-Espejo, García-Cadenas, Garcia-Gutierrez, Aroca, Chorao, Olave, Lopez-Jimenez, Gómez, Arellano, Cuesta-Casas, Avendaño-Pita, González-Santillana, Hernández-Rivas, Roldán-Pérez, Mico-Cerdá, Guerreiro, Morell, Rodriguez-Galvez, Labrador, Campos, Cedillo, Vidal, Martino and Solano.)

Competing Interests: None declared.

Competing Interests: None declared.

Chronic myelomonocytic leukemia (CMML) is frequently associated with mutations in the rat sarcoma gene (RAS), leading to worse prognosis. RAS mutations result in active RAS-GTP proteins, favoring myeloid cell proliferation and survival and inducing the NLRP3 inflammasome together with the apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), which promote caspase-1 activation and interleukin (IL)-1β release. Here, we report, in a cohort of CMML patients with mutations in KRAS, a constitutive activation of the NLRP3 inflammasome in monocytes, evidenced by ASC oligomerization and IL-1β release, as well as a specific inflammatory cytokine signature. Treatment of a CMML patient with a KRAS G12D mutation using the IL-1 receptor blocker anakinra inhibits NLRP3 inflammasome activation, reduces monocyte count, and improves the patient's clinical status, enabling a stem cell transplant. This reveals a basal inflammasome activation in RAS-mutated CMML patients and suggests potential therapeutic applications of NLRP3 and IL-1 blockers., Competing Interests: Declaration of interests P.P. is consultant of Viva In Vitro Diagnostics SL. P.P., H.M.-B., and C.G.-P. are inventors on patent PCT/EP2020/056729. L.H.-N., L.M.-A., H.M.-B., C.G.-P., and P.P. are co-founders of Viva In Vitro Diagnostics SL but declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Scarce data exist that analyze the outcomes of hematological patients with SARS-CoV-2 infection during the Omicron variant period who received treatment with remdesivir or nirmatrelvir/ritonavir., Methods: This study aims to address this issue by using a retrospective observational registry, created by the Spanish Hematopoietic Stem Cell Transplantation and Cell Therapy Group, spanning from 27 December 2021 to 30 April 2023., Results: This study included 466 patients, 243 (52%) who were treated with remdesivir and 223 (48%) with nirmatrelvir/ritonavir. Nirmatrelvir/ritonavir was primarily used for mild cases, resulting in a lower COVID-19-related mortality rate (1.3%), while remdesivir was preferred for moderate to severe cases (40%), exhibiting a higher mortality rate (9%). A multivariate analysis in the remdesivir cohort showed that male gender (odds ratio (OR) 0.35, p = 0.042) correlated with a lower mortality risk, while corticosteroid use (OR 9.4, p < 0.001) and co-infection (OR 2.8, p = 0.047) were linked to a higher mortality risk. Prolonged virus shedding was common, with 52% of patients shedding the virus for more than 25 days. In patients treated with remdesivir, factors associated with prolonged shedding included B-cell malignancy as well as underlying disease, severe disease, a later onset of and shorter duration of remdesivir treatment and a higher baseline viral load. Nirmatrelvir/ritonavir demonstrated a comparable safety profile to remdesivir, despite a higher risk of drug interactions., Conclusions: Nirmatrelvir/ritonavir proved to be a safe and effective option for treating mild cases in the outpatient setting, while remdesivir was preferred for severe cases, where corticosteroids and co-infection significantly predicted worse outcomes. Despite antiviral therapy, prolonged shedding remains a matter of concern.

Introduction: Oral anticoagulation (OAC) significantly mitigates thromboembolism risks in atrial fibrillation (AF) and venous thromboembolism (VTE) patients yet concern about major bleeding events persist. In fact, clinically relevant hemorrhages can be life-threatening. Bleeding risk is dynamic and influenced by factors such as age, new comorbidities, and drug therapies, and should not be assessed solely based on static baseline factors., Areas Covered: We comprehensively review the bleeding risk associated with OAC therapy. Emphasizing the importance of assessing both thromboembolic and bleeding risks, we present clinical tools for estimating stroke and systemic embolism (SSE) and bleeding risk in AF and VTE patients. We also address overlapping risk factors and the dynamic nature of bleeding risk., Expert Opinion: The OAC management is undergoing constant transformation, motivated by the primary objective of mitigating thromboembolism and bleeding hazards, thereby amplifying patient safety throughout the course of treatment. The future of OAC embraces personalized approaches and innovative therapies, driven by advanced pathophysiological insights and technological progress. This holds promise for improving patient outcomes and revolutionizing anticoagulation practices.