Incidence of All-Cause, Cardiovascular, and Atrial Fibrillation-Related Hospitalizations: Focus on Antiarrhythmic Drugs.

Background: Atrial fibrillation (AF) is associated with an increased risk of hospital admission, but few data on reasons for hospitalization and on the role of anti-arrhythmic drugs are available. Objectives: The purpose of this study was to investigate the incidence rate and factors associated with all-cause, cardiovascular, and AF-related hospitalizations. Methods: Prospective ongoing ATHERO-AF (Atherosclerosis in Atrial Fibrillation) cohort study enrolling AF patients on oral anticoagulants. Primary end points were all-cause, cardiovascular, and AF-related hospitalization, the latter defined as AF recurrences for paroxysmal AF and high-rate symptomatic AF episodes for persistent/permanent AF patients. Results: 2,782 patients were included (43.5% female; mean age was 74.6 ± 9.1 years). During a mean follow-up of 31 ± 26.8 months, 1,205 (12.1%/year) all-cause, 533 cardiac (5.7%/year), and 180 (2.0%/year) AF-related hospitalizations occurred. Predictors of AF-related hospitalizations were the use of flecainide/propafenone in both paroxysmal and persistent/permanent AF patients (HR: 1.861; 95% CI: 1.116 to 3.101 and 1.947; 95% CI: 1.069 to 3.548, respectively). Amiodarone (HR: 3.012; 95% CI: 1.835-4.943), verapamil/diltiazem (HR: 2.067; 95% CI: 1.117-3.825), and cancer (HR: 1.802; 95% CI: 1.057-3.070) but not beta-blockers and digoxin were associated with an increased risk of AF-related hospitalizations in persistent/permanent AF patients. Conclusions: Elderly AF patients frequently undergo hospitalizations for both cardiovascular and noncardiovascular causes. The use of anti-arrhythmic drugs was associated with an increased risk of AF-related hospitalization suggesting a scarce effect of these drugs in preventing AF episodes. Therefore, their use should be carefully considered and reserved for symptomatic patients with frequent AF recurrences.

Long-Term Risk of Hospitalization and Death in Patients With Mechanical Prosthetic Heart Valves.

Mechanical prosthetic heart valves (MPHVs) are commonly used for valvular heart disease in patients with a long life expectancy. Few longitudinal data on the specific causes of hospitalization in patients with MPHV are available. We investigated the risk of all-cause hospitalization and mortality in patients with MPHV. We performed a prospective, observational, ongoing study including consecutive patients with MPHVs who were referred to the atherothrombosis outpatient clinic of the Policlinico Umberto I of Rome for the vitamin K antagonist management. Study end points were all-cause, cardiovascular hospitalization, and overall mortality. We included 305 patients with MPHV (38.4% women, median age 60.2 years). The site of MPHV was aortic in 53.5%, mitral in 29.5%, and mitroaortic in 17%. During a median follow-up of 57.3 months, 142 hospitalizations occurred (8.16 per 100 person-years). The most common causes of hospitalization were cardiovascular disease (3.62 per 100 person-years), infections, surgery, and bleeding. The predictors of cardiovascular hospitalization were atrial fibrillation (hazard ratio [HR] 1.75, 95% confidence interval [CI] 1.04 to 2.95, p = 0.035), previous stroke/transient ischemic attack (HR 2.96, 95% CI 1.59 to 5.48, p = 0.001), and peripheral artery disease (HR 2.42, 95% CI 1.09 to 5.36, p = 0.030). During a median follow-up of 97.2 months, 61 deaths occurred (2.43 per 100 person-years). Age was directly associated with the risk of death (HR 1.088, 95% CI 1.054 to 1.122, p <0.001), whereas the time in therapeutic range higher than the median was inversely associated (HR 0.436, 95% CI 0.242 to 0.786, p = 0.006). In conclusion, patients with MPHV had a high incidence of hospitalizations, especially cardiovascular-related. The incidence of death is high; however, it may be decreased by maintaining a good quality of anticoagulation.

ACEF vs PARIS score in Predicting Cardiovascular Events in Patients With Acute Coronary Syndrome: Insights From the START ANTIPLATELET Registry.

Several scores can predict clinical outcomes of patients with Acute Coronary Syndromes (ACS). The validated PARIS (Patterns of Non-Adherence to Anti-Platelet Regimen in Stented Patients) score is poorly used in clinical practice because it needs items that are not always easily available. The ACEF (Age, Creatinine, and Ejection Fraction) score is more attractive because it only includes three items. We compared these scores to risk-stratify ACS patients enrolled into the START (Survey on anticoagulated pAtients RegisTer)-ANTIPLATELET registry. ACS patients who completed 1-year follow-up (n = 1171) were grouped in tertiles (low, medium, and high-risk) according to their ACEF/PARIS scores. Primary endpoints were: one-year MACCE (major adverse cardiac and cerebrovascular events: death, non-fatal myocardial infarction, stroke or target vessel revascularization) and NACE (net adverse cardiac and cerebrovascular events): MACCE plus major bleeding). MACCE incidence was higher in the high-risk tertile (15%) VS low/medium (3/7 %) risk tertiles (P < .001). NACE incidence in the high-risk tertile was 24% VS low/medium (9/15 %) risk tertiles (P < .001), independently of the risk score used. The ACEF score has similar accuracy as the validated PARIS score for the estimation of ischemic/bleeding risk. Thereby, we strongly suggest its use in clinical practice to risk-stratify ACS patients and select optimal therapeutic strategies.

Usefulness of the C2HEST score to predict new onset atrial fibrillation. A systematic review and meta-analysis on >11 million subjects.

BACKGROUND: The incidence of new-onset atrial fibrillation (NOAF) is increasing in the last decades. NOAF is associated with worse long-term prognosis. The C2HEST score has been recently proposed to stratify the risk of NOAF. Pooled data on the performance of the C2HEST score are lacking. METHODS: Systematic review and meta-analysis of observational studies reporting data on NOAF according to the C2HEST score. We searched PubMed, Web of Science and Google scholar databases without time restrictions until June 2023 according to PRISMA guidelines. Meta-analysis of the area under the curve (AUC) with 95% confidence interval (95% CI) and a sensitivity analysis according to setting of care and countries were performed. RESULTS: Of 360 studies, 17 were included in the analysis accounting for 11,067,496 subjects/patients with 307,869 NOAF cases. Mean age ranged from 41.3 to 71.2 years. The prevalence of women ranged from 10.6 to 54.75%. The pooled analysis gave an AUC of .70 (95% CI .66-.74). A subgroup analysis on studies from general population/primary care yielded an AUC of 0.69 (95% CI 0.64-0.75). In the subgroup of patients with cardiovascular disease, the AUC was .71 (.69-.79). The C2HEST score performed similarly in Asian (AUC .72, 95% CI .68-.77), and in Western patients (AUC .68, 95% CI .62-.75). The best performance was observed in studies with a mean age <50 years (n = 3,144,704 with 25,538 NOAF, AUC .78, 95% CI .76-.79). CONCLUSION: The C2HEST score may be used to predict NOAF in primary and secondary prevention patients, and in patients across different countries. Early detection of NOAF may aid prompt initiation of management and follow-up, potentially leading to a reduction of AF-related complications.

Risk of venous thromboembolism and arterial events in patients with hypoalbuminemia: a comprehensive meta-analysis of more than 2 million patients.

BACKGROUND: Albumin has antiplatelet and anticoagulant functions. Hypoalbuminemia, as defined by serum values of <3.5 g/dL, is associated with arterial thrombosis; its impact on venous thromboembolism (VTE) is unclear. OBJECTIVES: The objective of this meta-analysis is to assess the VTE risk in patients with hypoalbuminemia. METHODS: MEDLINE and EMBASE were searched up to January 2024 for observational studies and randomized trials reporting data of interest. Primary outcome was the risk of VTE, while secondary outcomes were myocardial infarction and stroke risk in patients with hypoalbuminemia versus those without hypoalbuminemia. The risk of bias was evaluated using Newcastle-Ottawa scale and Cochrane tool. Risk ratios (RRs) with 95% confidence intervals (CIs) were calculated in a random-effects model. RESULTS: Forty-three studies for a total of 2 531 091 patients (39 738 medical and 2 491 353 surgical) were included in primary analysis; 79.1% of the studies used 3.5 g/dL cut-off value for hypoalbuminemia definition. Follow-up duration was 30 days in 60.5% of studies. Patients with hypoalbuminemia had a higher risk of VTE (RR, 1.88; 95% CI, 1.66-2.13). RRs were similar in both medical (RR, 1.87; 95% CI, 1.53-2.27) and surgical patients (RR, 1.87; 95% CI, 1.61-2.16) and in patients with (RR, 1.86; 95% CI, 1.66-2.10) and without cancer (RR, 1.89; 95% CI, 1.47-2.44). Risk of myocardial infarction (RR, 1.88; 95% CI, 1.54-2.31) and stroke (RR, 1.77; 95% CI, 1.26-2.48) was higher in patients with hypoalbuminemia. CONCLUSION: Hypoalbuminemia is a risk factor for VTE in both medical and surgical patients irrespective of cancer coexistence. Serum albumin analysis may represent a simple and cheap tool to identify patients at VTE risk.

The association between hypoalbuminemia and risk of death due to cancer and vascular disease in individuals aged 65 years and older: findings from the prospective Moli-sani cohort study.

Background: Serum albumin is inversely associated with overall mortality, but its association with specific causes of death remains uncertain. This study aims to investigate whether hypoalbuminemia, defined as serum albumin levels ≤35 g/L, is associated with mortality specifically attributed to cancer and/or vascular diseases. Methods: Serum albumin levels were measured in the population-based, prospective cohort of the Moli-sani study, established between 2005 and 2010. Hypoalbuminemia was defined as serum albumin levels ≤35 g/L. Cause-specific mortality was assessed using the validated Italian mortality registry and coded according to the International Classification of Diseases, Revision 9. Over a median follow-up period of 13.1 years, the relationship between serum albumin and mortality, adjusted for covariates, was investigated using competing-risk survival analysis. Findings: The analysed cohort comprised 17,930 individuals aged ≥35 years, of whom 8445 were men (47.1%). The mean age was 54 years (standard deviation (SD) = 11 years), with 3299 individuals (18.4%) aged older than 65 years. All participants had C-reactive protein levels <10 mg/L and no history of liver, renal, cardiovascular, or cancer disease. Hypoalbuminemia was found in 406 individuals (2.3%). The study documented a total of 1428 deaths, with 574 attributed to cancer and 464 to vascular causes. Hypoalbuminemia was independently associated with mortality when compared to serum albumin >40 g/L (Hazard Ratio (HR) = 1.61, 95% Confidence Interval: 1.21-2.13). A decrease of 1-SD in serum albumin levels corresponded to HR of 1.16 (1.09-1.22), 1.16 (1.05-1.28), and 1.13 (1.03-1.23) for total, vascular and cancer mortality, respectively. Upon stratifying by age, hypoalbuminemia was associated with total mortality solely in those aged ≥65 years (HR = 1.83; 1.33-2.50) but not in the <65 years group (HR = 1.03; 0.53-2.00; P < 0.0001 for difference). Similar age-related patterns emerged for vascular death (per 1-SD decrease HR = 1.19; 1.07-1.33 in individuals ≥65 years and HR = 1.05; 0.86-1.29 in individuals <65 years) and cancer mortality (HR = 1.15; 1.02-1.30; ≥65 years and HR = 1.08; 0.96-1.23; <65 years). Interpretation: Individuals ≥65 years old with serum albumin levels ≤35 g/L are at higher risk of total, cancer, and vascular mortality. Funding: This paper was developed within the project funded by Next Generation EU-"Age-It - Ageing well in an ageing society" project (PE0000015), National Recovery and Resilience Plan (NRRP)-PE8-Mission 4, C2, Intervention 1.3.

Low platelet count at admission has an adverse impact on outcome in patients with acute coronary syndromes: from the START Antiplatelet registry.

Some previous observations suggest that a low platelet count is associated with an increased risk of adverse outcomes in patients with acute coronary syndromes (ACS). However, most of the data come from post-hoc analyses of randomized controlled trials and from studies including thrombocytopenia developed during hospital stay. Our aim was to assess the impact of low platelet count at admission on cardiovascular outcomes and treatment approach in patients hospitalized for ACS in a current real-life setting in Italy. Patients admitted to Italian coronary care units for ACS were enrolled in the START-ANTIPLATELET registry. Baseline clinical characteristics and treatment at discharge were recorded. Patients were followed-up at 6 months, 1 year and yearly thereafter. Low platelet count was defined as a count at admission < 150 > 100 k/µl or < 100 k/µL. Among 1894 enrolled patients, 157 (8.3%) had a platelet count < 150 > 100 k/µl and 30 (1.6%) < 100 k/µl. The median follow-up was 12.3 months (0.4-50.1). patients with low platelets were older (72 ± 10.4 vs 66 ± 12.4 years, p = 0.006), more frequently males (82.9 vs 72.1%, p = 0.001), hypertensive (90.0% vs 70.4%, p = 0.03), with non-valvular atrial fibrillation (NVAF) (17.1 vs 8.6%, p = 0.02), and peripheral arterial disease (11.5 vs 6.2% p = 0.01) and/or had a previous myocardial infarction (40 vs 18.7%, p = 0.008) and/or a PCI (14.6 vs 7.8%, p = 0.001) than patients with normal platelets. A slightly, but significantly, lower percentage of thrombocytopenic patients were treated with primary PCI (78.1 vs 84.4%, p = 0.04) and they were more frequently discharged on aspirin plus clopidogrel rather than aspirin plus newer P2Y12 antagonists (51.9 vs 65.4%, p = 0.01). MACE-free survival was significantly shorter in thrombocytopenic patients compared to patients with normal platelets (< 150 > 100 k/µl: 37.6 vs 41.8 months, p = 0.002; HR = 2.7, 95% CIs 1.4-5.2; < 100 k/µl: 31.7 vs 41.8 months, p = 0.01; HR = 6.5, 95% CIs 1.5-29.1). At multivariate analysis, low platelet count, age at enrollment, low glomerular filtration rate, low ejection fraction, a previous ischemic stroke and NVAF were independent predictors of MACE. A low platelet count at admission identifies a subgroup of ACS patients with a significantly increased risk of MACE and these patients should be managed with special care to prevent excess adverse outcomes.

Oleuropein, a Component of Extra Virgin Olive Oil, Improves Liver Steatosis and Lobular Inflammation by Lipopolysaccharides-TLR4 Axis Downregulation.

Gut-dysbiosis-induced lipopolysaccharides (LPS) translocation into systemic circulation has been suggested to be implicated in nonalcoholic fatty liver disease (NAFLD) pathogenesis. This study aimed to assess if oleuropein (OLE), a component of extra virgin olive oil, lowers high-fat-diet (HFD)-induced endotoxemia and, eventually, liver steatosis. An immunohistochemistry analysis of the intestine and liver was performed in (i) control mice (CTR; n = 15), (ii) high-fat-diet fed (HFD) mice (HFD; n = 16), and (iii) HFD mice treated with 6 µg/day of OLE for 30 days (HFD + OLE, n = 13). The HFD mice developed significant liver steatosis compared to the controls, an effect that was significantly reduced in the HFD + OLE-treated mice. The amount of hepatocyte LPS localization and the number of TLR4+ macrophages were higher in the HFD mice in the than controls and were lowered in the HFD + OLE-treated mice. The number of CD42b+ platelets was increased in the liver sinusoids of the HFD mice compared to the controls and decreased in the HFD + OLE-treated mice. Compared to the controls, the HFD-treated mice showed a high percentage of intestine PAS+ goblet cells, an increased length of intestinal crypts, LPS localization and TLR4+ expression, and occludin downregulation, an effect counteracted in the HFD + OLE-treated mice. The HFD-fed animals displayed increased systemic levels of LPS and zonulin, but they were reduced in the HFD + OLE-treated animals. It can be seen that OLE administration improves liver steatosis and inflammation in association with decreased LPS translocation into the systemic circulation, hepatocyte localization of LPS and TLR4 downregulation in HFD-induced mouse model of NAFLD.

Risk of adverse events in anticoagulated patients with atrial fibrillation and non-alcoholic fatty liver disease.

BACKGROUND: The clinical impact of Nonalcoholic fatty liver disease(NAFLD) in patients with atrial fibrillation(AF) is still controversial. AIM: To evaluate the 1-year risk of all-cause death, thromboembolic events, and bleeding in AF-NAFLD patients. METHODS: Retrospective study with a health research network(TriNetX). AF patients on oral anticoagulation(OAC) were categorized according to the presence of NAFLD into two groups. The primary outcomes were the 1-year risks of: i) a composite cardiovascular outcome (all-cause death, myocardial infarction, stroke, cardiac arrest, and pulmonary embolism); and ii) a composite hemorrhagic outcome(intracranial hemorrhage and gastrointestinal bleeding). Cox regression analysis before and after propensity-score-matching(PSM) was used to estimate Hazard Ratio(HR) and 95% confidence intervals(95%CI). Sensitivity analyses investigated the risk associated with cirrhosis, thrombocytopenia, and type of OAC(warfarin vs non-vitamin K antagonist oral anticoagulants(NOAC). RESULTS: We identified 22,636 AF-NAFLD patients (69±12 years, 46.7% females) and 391,014 AF patients without liver disease(72±12 years, 42.7% females). NAFLD was associated with a higher risk of composite cardiovascular (HR 1.54,95%CI 1.47-1.61) and hemorrhagic (HR 1.56,95%CI 1.42-1.72) outcomes. This was consistent also for all the single outcomes. Cirrhotic and thrombocytopenic AF-NAFLD patients showed the highest risks. Compared to AF-NAFLD patients on NOAC, those on warfarin were associated with a higher risk of cardiovascular and hemorrhagic outcomes. CONCLUSION: In AF patients, NAFLD is associated with a higher 1-year risk of adverse events, with the risk of adverse events progressively increasing from non-cirrhotic to cirrhotic and from non-thrombocytopenic to thrombocytopenic patients. NOACs were associated with a better effectiveness and safety profile compared to warfarin.

Statin use is associated with a lower risk of all-cause death in patients with breast cancer treated with anthracycline containing regimens: a global federated health database analysis.

Anthracyclines are associated with enhanced oxidative stress responsible for adverse events in patients with breast cancer. However, no study has investigated the potential anti-inflammatory role of statins in counteracting anthracycline toxicity. In this retrospective study utilizing a federated health network (TriNetX), patients with breast cancer (ICD code C50) treated with anthracyclines were categorized into two groups: statin users (for at least 6 months); and statin non-users. The primary outcome was the 5-year risk of all-cause death. Secondary outcomes were the risk of myocardial infarction, stroke, atrial fibrillation, ventricular arrhythmias, heart failure, and pulmonary embolism. Cox-regression analyses were used to produce hazard ratios (HRs) and 95% confidence intervals (CI) following 1:1 propensity score matching (PSM). We identified 3,701 statin users (68.8 ± 10.4 years) and 37,185 statin non-users (59.6 ± 12.8 years). After PSM, the 5-year risk of all-cause death was significantly lower in statin users (HR 0.82, 95% CI 0.74-0.91) compared to statins non-users. Analyzing the risk for secondary outcomes, only the risk of stroke was significantly increased in statin users (HR 1.27, 95% CI 1.01-1.61), while no associations were found for the other cardiovascular events. The risk of all-cause death in statin users was the lowest during the first year after the anthracycline's initiation. No significant difference was found between lipophilic and hydrophilic statins. In patients with breast cancer treated with anthracyclines, statin use is associated with a reduced risk of all-cause death. Prospective studies are needed to investigate the potential beneficial effect of statin initiation in cancer patients without other indications.

Pathogenesis of Hemophagocytic Lymphohistiocytosis/Macrophage Activation Syndrome: A Case Report and Review of the Literature.

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening condition characterized by the uncontrolled activation of cytotoxic T lymphocytes, NK cells, and macrophages, resulting in an overproduction of pro-inflammatory cytokines. A primary and a secondary form are distinguished depending on whether or not it is associated with hematologic, infectious, or immune-mediated disease. Clinical manifestations include fever, splenomegaly, neurological changes, coagulopathy, hepatic dysfunction, cytopenia, hypertriglyceridemia, hyperferritinemia, and hemophagocytosis. In adults, therapy, although aggressive, is often unsuccessful. We report the case of a 41-year-old man with no apparent history of previous disease and an acute onset characterized by fever, fatigue, and weight loss. The man was from Burkina Faso and had made trips to his home country in the previous five months. On admission, leukopenia, thrombocytopenia, increased creatinine and transaminases, LDH, and CRP with a normal ESR were found. The patient also presented with hypertriglyceridemia and hyperferritinemia. An infectious or autoimmune etiology was ruled out. A total body CT scan showed bilateral pleural effusion and hilar mesenterial, abdominal, and paratracheal lymphadenopathy. Lymphoproliferative disease with HLH complication was therefore suspected. High doses of glucocorticoids were then administered. A cytologic analysis of the pleural effusion showed anaplastic lymphoma cells and bone marrow aspirate showed hemophagocytosis. An Epstein-Barr Virus (EBV) DNA load of more than 90000 copies/mL was found. Bone marrow biopsy showed a marrow localization of peripheral T lymphoma. The course was rapidly progressive until the patient died. HLH is a rare but usually fatal complication in adults of hematologic, autoimmune, and malignant diseases. Very early diagnosis and treatment are critical but not always sufficient to save patients.

MORE EARLY BLEEDS ASSOCIATED WITH HIGH BASELINE DIRECT ORAL ANTICOAGULANT LEVELS IN ATRIAL FIBRILLATION: THE MAS STUDY.

Treatment with direct oral anticoagulants (DOAC) in atrial fibrillation (AF) patients is effective and safe. However, bleeding complications still occur. Whether the measurement of DOAC levels may further improve treatment efficacy and safety is still an open issue. In the "Measure and See" (MAS) Study (#NCT03803579) venous blood was collected 15-30 days after DOAC initiation in AF patients who were then followed for one year to record the occurrence of major and clinically relevant non-major bleeding. DOAC plasma levels were measured in one laboratory, and results were kept blind to patients and treating doctors. Trough DOAC levels were assessed in 1657 patients [957 (57.7%) and 700 treated with standard and low-dose, respectively]. Fifty bleeding events were recorded during 1606 years of follow-up (3.11% pt/yrs). Fifteen bleeding events (4.97% pt/yrs) occurred in patients with C-trough standardized values in the highest activity class (> 0.50); whereas 35 events (2.69% pt/yrs) occurred in those with values in the two lower classes ( 0.50, p= 0.0401). Increasing DOAC levels and low-dose DOAC use were associated with increased bleeding risk in the first three months of treatment. 19% of patients receiving low doses had standardized activity values in the highest class. More bleeding occurred in patients treated with low (4.3% pt/yrs) than standard (2.2% pt/yrs; p= 0.0160) dose DOAC. Early measurement of DOAC levels in AF patients identified many subjects with high activity levels despite the low doses use and had more bleeding risk during the first 3 months of treatment.

Prediction of new-onset atrial fibrillation with the C2HEST score in patients admitted with community-acquired pneumonia.

PURPOSE: Patients hospitalized for community-acquired pneumonia (CAP) may have a higher risk of new-onset atrial fibrillation (NOAF). The C2HEST score was developed to evaluate the NOAF risk in the general population. Data on the value of the C2HEST score in acute patients admitted with CAP are lacking. We want to establish the predictive value of C2HEST score for NOAF in patients with CAP. METHODS: Patients with CAP enrolled in the SIXTUS cohort were enrolled. C2HEST score was calculated at baseline. In-hospital NOAF was recorded. Receiver-operating Characteristic (ROC) curve and multivariable Cox proportional hazard regression analysis were performed. RESULTS: We enrolled 473 patients (36% women, mean age 70.6 ± 16.5 years), and 54 NOAF occurred. Patients with NOAF were elderly, more frequently affected by hypertension, heart failure, previous stroke/transient ischemic attack, peripheral artery disease and hyperthyroidism. NOAF patients had also higher CURB-65, PSI class and CHA2DS2-VASc score. The C-index of C2HEST score for NOAF was 0.747 (95% confidence interval [95%CI] 0.705-0.786), higher compared to CURB-65 (0.611, 95%CI 0.566-0.655, p = 0.0016), PSI (0.665, 95%CI 0.621-0.708, p = 0.0199) and CHA2DS2-VASc score (0.696, 95%CI 0.652-0.737, p = 0.0762). The best combination of sensitivity (67%) and specificity (70%) was observed with a C2HEST score ≥ 4. This result was confirmed by the multivariable Cox analysis (Hazard Ratio [HR] for C2HEST score ≥ 4 was 10.7, 95%CI 2.0-57.9; p = 0.006), independently from the severity of pneumonia. CONCLUSION: The C2HEST score was a useful predictive tool to identify patients at higher risk for NOAF during hospitalization for CAP. CLINICAL TRIAL REGISTRATION: www. CLINICALTRIALS: gov (NCT01773863).

Low-dose azithromycin prophylaxis in patients with atrial fibrillation and chronic obstructive pulmonary disease.

Low-dose azithromycin prophylaxis is associated with improved outcomes in people suffering frequent exacerbations of chronic obstructive pulmonary disease (COPD), but the use of macrolides in patients with cardiovascular disease has been debated. To investigate the risk of adverse events after COPD exacerbations in patients with atrial fibrillation (AF) treated with azithromycin prophylaxis. Retrospective cohort study within the TriNetX Platform, including AF patients with COPD exacerbations. Risks of primary and secondary outcomes were recorded up to 30 days post-COPD exacerbations and compared between azithromycin users and azithromycin non-users. The primary outcomes were the risks for a composite of (1) cardiovascular (all-cause death, heart failure, ventricular arrhythmias, ischemic stroke, myocardial infarction, and cardiac arrest), and (2) hemorrhagic events (intracranial hemorrhage (ICH), and gastro-intestinal bleeding). Cox-regression analyses compared outcomes between groups after propensity score matching (PSM). After PSM, azithromycin users (n = 2434, 71 ± 10 years, 49% females) were associated with a lower 30-day risk of post-exacerbation cardiovascular (HR 0.67, 95% CI 0.61-0.73) and hemorrhagic composite outcome (HR 0.45, 95% CI 0.32-0.64) compared to azithromycin non-users (n = 2434, 72 ± 11 years, 51% females). The beneficial effect was consistent for each secondary outcomes, except ICH. On sensitivity analyses, the reduced risk of adverse events in azithromycin users was irrespective of smoking status, exacerbation severity, and type of oral anticoagulation. Azithromycin prophylaxis is associated with a lower risk of all-cause death, thrombotic and hemorrhagic events in AF patients with COPD. The possible role of azithromycin prophylaxis as part of the integrated care management of AF patients with COPD needs further study.

Acute upper and lower gastrointestinal bleeding management in older people taking or not taking anticoagulants: a literature review.

Acute upper and lower gastrointestinal (GI) bleeding may be a potentially life-threatening event that requires prompt recognition and an early effective management, being responsible for a considerable number of hospital admissions. Methods. We perform a clinical review to summarize the recent international guidelines, helping the physician in clinical practice. Older people are a vulnerable subgroup of patients more prone to developing GI bleeding because of several comorbidities and polypharmacy, especially related to an increased use of antiplatelet and anticoagulant drugs. In addition, older patients may have higher peri-procedural risk that should be evaluated. The recent introduction of reversal strategies may help the management of GI bleeding in this subgroup of patients. In this review, we aimed to (1) summarize the epidemiology and risk factors for upper and lower GI bleeding, (2) describe treatment options with a focus on pharmacodynamics and pharmacokinetics of different proton pump inhibitors, and (3) provide an overview of the clinical management with flowcharts for risk stratification and treatment. In conclusion, GI is common in older patients and an early effective management may be helpful in the reduction of several complications.

NOX2 as a Biomarker of Academic Performance: Evidence from University Students during Examination.

BACKGROUND: Cortisol levels, oxidative stress, and lower cerebral performance seem to be closely related. This study aimed to evaluate the question of whether exam stress affected oxidative stress and endothelial function parameters in the salivary samples of students. METHODS: A total of 114 healthy students were recruited. All students were subjected to a 21-item DASS questionnaire to assess perceived stress. Cortisol levels, biomarkers of oxidative stress, and endothelial function were evaluated at T0, during the semester, and T1, in the morning before the exam, in saliva samples. In vitro, HUVECs were stimulated with cortisol, and oxidative stress and endothelial function parameters were evaluated. RESULTS: At T1, cortisol levels were significantly increased compared with the levels during the semester. Moreover, exam results correlated inversely with the DASS score at T1. In addition, NOX2, H2O2 and endothelin-1 significantly increased, while NO bioavailability decreased. In vitro, HUVECs treatment with human cortisol determined the increase of oxidative stress and the decrease of endothelial function, in association with impaired eNOS phosphorylation. CONCLUSION: NOX2-mediated oxidative stress is a mechanism that could mediate cortisol-induced transient endothelial dysfunction during academic examination. Therefore, strategies to monitor or modulate oxidative stress could help students to reduce the impact of examination-related stress.

Midregional-proAdrenomedullin as a prognostic tool in sepsis and septic shock: A systematic review and meta-analysis.

BACKGROUND: Midregional-proAdrenomedullin (MR-proADM) has been recently proposed as a tool in patients with sepsis and septic shock. Our aim was to evaluate the prognostic role of MR-proADM in hospitalized patients with sepsis and septic shock. METHODS: PRISMA guideline was followed. MEDLINE and EMBASE were searched up to June 2023. Primary outcome was mean difference in MR-proADM among survivors and nonsurvivors, secondary outcome mean difference in MR-proADM according to infection severity and type. Risk of bias was evaluated using Newcastle-Ottawa scale for observational studies and Cochrane tool for randomized trials. Pooled mean differences (MD) with corresponding 95% confidence intervals (CIs) were calculated in a random-effects model. RESULTS: Twenty-four studies included 6730 adult patients (1208 nonsurvivors and 5522 survivors) and three studies included 195 paediatric patients (30 nonsurvivors and 165 survivors). A total of 10, 4 and 13 studies included, respectively, patients with sepsis (3602 patients), septic shock (386 patients) and a mixed population (2937 patients). Twenty-one studies included patients with different source of infection, three with pneumonia and one with a catheter-related infection. Most studies (n = 12) had a follow-up of 28 days. In adult cohort, pooled mean difference between nonsurvivors and survivors of MR-proADM was 2.55 mmol/L (95% CI: 1.95-3.15) with higher values in patients with septic shock (4.25 mmol/L; 95% CI, 2.23-6.26 mmol/L) than in patients with sepsis (1.77 mmol/L; 95% CI: 1.11-2.44 mmol/L). In paediatric cohort, pooled mean difference was 3.11 mmol/L (95% CI: -0.02-6.24 mmol/L). CONCLUSIONS: Higher values of MR-proADM are detectable in nonsurvivors adult and paediatric-hospitalized patients with sepsis or septic shock.

Inappropriate Underdosing of Direct Oral Anticoagulants in Atrial Fibrillation Patients: Results from the START2-AF Registry.

Background: Direct oral anticoagulants (DOACs) are recommended for stroke prevention in non-valvular atrial fibrillation (NVAF) patients. We aimed to describe the prevalence of inappropriate DOACs dose prescription in the START2-AF Registry, the outcomes according to the appropriateness of the dosage, and the factors associated with inappropriate dose prescription. Methods: Patients' demographics and clinical data were prospectively collected as electronic files in an anonymous form on the website of the START2-Registry; DOACs dosage was determined to be appropriate when prescribed according to the European Heart Rhythm Association Guidelines. Results: We included 5943 NVAF patients on DOACs; 2572 (46.3%) were female patients. The standard dose (SD) was prescribed to 56.9% of patients and the low dose (LD) was prescribed to 43.1% of patients; 38.9% of all NVAF patients received an inappropriate LD DOAC and 0.3% received inappropriate SD. Patients treated with LD DOAC had a significantly higher rate of all bleedings (RR 1.5; 95% CI 1.2-2.0), major bleedings (RR 1.8; 95% CI 1.3-1.7), and mortality (RR 2.8; 95% CI 1.9-4.1) with respect to patients treated with SD DOAC. No difference was found among patients treated with appropriate and inappropriate LD regarding bleeding, thrombotic, and mortality rates. Age, body weight <60 kg, and renal failure were significantly associated with inappropriate LD DOAC prescription. Conclusions: Inappropriate LD DOACs in NVAF patients is not associated with a reduction in bleeding risk, nor with an increased thrombotic risk. Instead, it is associated with higher mortality rate, suggesting that, in clinical practice, underdosing is preferred for patients at particularly high risk for adverse events.