Impact of atrial fibrillation and anticoagulation on the risk of death, thromboembolic disease and bleeding in patients with COVID-19: the ACO-VID Registry.

OBJECTIVE: To describe the clinical profile, risk of complications and impact of anticoagulation in COVID-19 hospitalized patients, according to the presence of atrial fibrillation (AF). METHODS: Multicenter, retrospective, and observational study that consecutively included patients >55 years admitted with COVID-19 from March to October 2020. In AF patients, anticoagulation was chosen based on clinicians' judgment. Patients were followed-up for 90 days. RESULTS: A total of 646 patients were included, of whom 75.2% had AF. Overall, mean age was 75 ± 9.1 years and 62.4% were male. Patients with AF were older and had more comorbidities. The most common anticoagulants used during hospitalization in patients with AF were edoxaban (47.9%), low molecular weight heparin (27.0%), and dabigatran (11.7%) and among patients without AF, these numbers were 0%, 93.8% and 0%. Overall, during the study period (68 ± 3 days), 15.2% of patients died, 8.2% of patients presented a major bleeding and 0.9% had a stroke/systemic embolism. During hospitalization, patients with AF had a higher risk of major bleeding (11.3% vs 0.7%; p < .01), COVID-19-related deaths (18.0% vs 4.5%; p = .02), and all-cause deaths (20.6% vs 5.6%; p = .02). Age (HR 1.5; 95% CI 1.0-2.3) and elevated transaminases (HR 3.5; 95% CI 2.0-6.1) were independently associated with all-cause mortality. AF was independently associated with major bleeding (HR 2.2; 95% CI 1.1-5.3). CONCLUSIONS: Among patients hospitalized with COVID-19, patients with AF were older, had more comorbidities and had a higher risk of major bleeding. Age and elevated transaminases during hospitalization, but not AF nor anticoagulant treatment increased the risk of all-cause death.

Impact of New Onset Atrial Fibrillation in Hospitalized Patients with COVID-19. Results of the "ACO-VID" Registry.

OBJECTIVE: To assess the impact of new-onset atrial fibrillation (AF) on patients hospitalized with coronavirus disease 2019 (COVID-19). METHODS: Multicenter and retrospective study that included subjects >55 years hospitalized with COVID-19 from March to October 2020 in Spanish hospitals. Patients were divided into 3 groups (no AF, new-onset AF, and preexisting AF) and followed-up to 90 days. RESULTS: A total of 668 patients were included, of whom 162 (24.3%) had no AF, 107 (16.0%) new-onset AF and 399 (59.7%) preexisting AF. Compared to patients without AF, those patients with new-onset AF were older and had more comorbidities, but without differences with preexisting AF. During hospitalization, in the univariate analysis, compared to patients without AF, major bleeding and cardiovascular mortality were more frequent in patients with new-onset AF (10.3% vs 0.6%; P < .001; 2.8% vs 0.6%; P = .025, respectively), with a trend toward more stroke (1.9% vs 0%; P = .085). Outcomes were similar between AF groups, but the length of stay was greater in preexisting AF patients. Among patients with new-onset AF taking reduced doses of anticoagulant treatment was associated with higher risks of stroke and major bleeding. CONCLUSIONS: In COVID-19 hospitalized patients, new-onset AF may be associated with worse outcomes, but influenced by the dose of anticoagulants.

Role of GSTT1 and M1 null genotypes as risk factors for B-cell lymphoma: influence of geographical factors and occupational exposure.

The interrelationship between genetic susceptibility and carcinogenic exposure is important in the development of haematopoietic malignancies. Both factors need to be considered to enable assessment of disease risk associated with a given individual under certain environmental conditions. GSTT1 and GSTM1 are two genes whose proteins are involved in the detoxification of potential carcinogens. We have studied the prevalence of GSTT1 and GSTM1 null polymorphisms using a novel PCR multiplex protocol in a group of 158 patients with B-cell lymphoma (BCL, 138 with non-Hodgkin lymphoma and 20 with Hodgkin lymphoma) and 214 healthy controls. A questionnaire regarding occupational exposure and lifestyle factors was also completed by both groups. GSTM1 null genotype showed no significant differences between patients and controls (46.9% and 55.6%, respectively). In contrast, GSTT1 null genotype was observed in 25.3% of patients and 15.4% of controls (P=0.013; OR=1.85; CI (95%):1.11-3.09), suggesting a role for the GSTT1 null genotype in the development of BCL. This effect was even more evident in females (27.5% vs. 14%: P=0.014). No significant association was observed between GST genotypes and disease risk in relation to smoking or occupational exposure.

Dabigatran in patients with atrial fibrillation after COVID-19 hospitalization: an update of the ANIBAL protocol.

COVID-19 increases the risk of atrial fibrillation (AF) and thrombotic complications, particularly in severe cases, leading to higher mortality rates. Anticoagulation is the cornerstone to reduce thromboembolic risk in patients with AF. Considering the risk of hepatotoxicity in patients with severe COVID-19 as well as the risk of drug-drug interactions, drug-induced hepatotoxicity and bleeding, the ANIBAL protocol was developed to facilitate the anticoagulation approach at discharge after COVID-19 hospitalization. However, since the publication of the original algorithm, relevant changes have occurred. First, treatment of COVID-19 pneumonia has been modified with the use of dexamethasone or remdesivir during the first week in patients that require oxygen therapy, and of dexamethasone and/or tocilizumab or baricitinib during the second week in patients that necessitate supplementary oxygen or with a high inflammation state, respectively. On the other hand, metabolic syndrome is common in patients with AF as well as metabolic-associated fatty liver disease, and this could negatively impact the prognosis of patients with COVID-19, including high transaminase levels in patients treated with immunomodulators. The EHRA guidelines update also introduce some interesting changes in drug-drug interaction patterns with the reduction of the level of the interaction with dexamethasone, which is of paramount importance in this clinical context. Considering the new information, the protocol, named ANIBAL II, has been updated. In this new protocol, the anticoagulant of choice in patients with AF after COVID-19 hospitalization is provided according to three scenarios: with/without dexamethasone treatment at discharge and normal hepatic function, transaminases ≤2 times the upper limit of normal, or transaminases >2 times the upper limit of normal.

Efficacy and tolerability of oral iron protein succinylate: a systematic review of three decades of research.

Objective: Oral supplementation with iron is a standard intervention for treating or preventing iron deficiency with or without anemia. Over the last few decades, various forms of oral iron have been developed to improve treatment tolerability and iron bioavailability. In this review, we gathered research data regarding the use of iron protein succinylate since it was first marketed in the 1980s.Methods: Electronic databases - PubMed and the Cochrane Library - were searched for studies published up to March 2019. Clinical or observational studies reporting data on the tolerability of oral iron protein succinylate were included. Results were statistically described to evaluate and compare the efficacy and safety of iron protein succinylate with the comparators under study.Results: Iron protein succinylate was investigated in 54 studies: 38 randomized clinical trials and 16 observational studies, with a total of 8454 subjects. Of them, 8142 were included in the efficacy analysis: patients were divided into three population subtypes: general (n = 1899), gynecological/obstetric (n = 5283), and pediatric (n = 960). In total, 6450 patients received iron protein succinylate, experiencing a significant change in hemoglobin and ferritin in all populations. The change in all parameters was similar or higher with iron protein succinylate compared to other iron treatments evaluated. Overall, study groups receiving iron protein succinylate reported the lowest rate of adverse events.Conclusions: Although all iron treatments analyzed are effective and safe, our results suggest that iron protein succinylate may be an excellent choice to treat iron deficiency and anemia due to its superior effectiveness and tolerability.

Dabigatran, the oral anticoagulant of choice at discharge in patients with non-valvular atrial fibrillation and COVID-19 infection: the ANIBAL protocol.

Atrial fibrillation is a frequent complication among patients with severe coronavirus disease-2019 (COVID-19) infection. Both direct and indirect mechanisms through COVID-19 have been described to explain this relationship. COVID-19 infection increases the risk of developing both arterial and venous thrombotic complications through systemic coagulation activation, leading to increased mortality. Chronic oral anticoagulation is essential to reduce the thromboembolic risk among AF patients. Switching to low-molecular-weight heparin has been recommended during hospitalization for COVID-19 infection. Of note, at discharge, the prescription of direct oral anticoagulants may offer some advantages over vitamin K antagonists. However, oral anticoagulants should only be prescribed after the consideration of drug-drug interactions with antiviral therapies as well as of the risk of hepatotoxicity, which is common among individuals with severe COVID-19 pneumonia. Not all anticoagulants have the same risk of hepatotoxicity; dabigatran has shown a good efficacy and safety profile and could have a lower risk of hepatotoxicity. Furthermore, its metabolism by cytochrome P450 is absent and it has a specific reversal agent. Therefore, dabigatran may be considered as a first-line choice for oral anticoagulation at discharge after COVID-19 infection. In this review, the available information on the antithrombotic management of AF patients at discharge after COVID-19 infection is updated. In addition, a practical algorithm, considering renal and liver function, which facilitates the anticoagulation choice at discharge is presented.

Erdheim-Chester disease mimicking multiple sclerosis or a new association?

Erdheim-Chester disease (ECD) is a rare form of non-Langerhans cell histiocytosis that presents potential impairment of the central nervous system (CNS). Frequent CNS impairment makes ECD a disease worth considering in the differential diagnosis of multiple sclerosis (MS). We report the case of a patient initially diagnosed with relapsing-remitting MS with an atypical course who developed ECD during the disease progression. Given the patient's clinical-radiological characteristics, two diagnostic possibilities were proposed: the coexistence of both diseases or a new presentation of ECD mimicking MS. We conducted a literature review, analyzing the various diagnostic and therapeutic possibilities.

Adverse effects of azacitidine: onset, duration, and treatment.

High-risk myelodysplastic syndromes present a poor prognosis, with survivals of close to only 1 year. The use of azacitidine, a DNA methyltransferase inhibitor, in this group of patients has transformed this grey image, with a demonstrated improvement in survival. Responses to survival are attained in a progressive manner, providing that the drug is used continually. This requires a good control of the adverse effects of the drug, which are primarily in the first cycles of treatment. The hematological adverse effects can be handled with transfusions and growth factors. The nonhematological adverse effects can be prevented with the use of antiemetics and a good technique of drug administration.