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The role of inflammation in predicting early cardiac complications among stroke patients is unclear. Electronic medical records from TriNetX, a global federated health research network, were used for this retrospective analysis. Patients with ischemic stroke and C-Reactive Protein (CRP) levels measured within 24 h post-stroke were categorized into three groups: (i) 3 mg/L. The primary outcome was a composite outcome of cardiac complications (heart failure (HF), ischemic heart disease, atrial fibrillation (AF), ventricular arrhythmias and Takotsubo cardiomyopathy) or death at 30 days from the index event. Cox-regression analyses were used to produce hazard ratios (HRs) and 95% confidence intervals (CI) following 1:1 propensity score matching (PSM). Of the 104,741 patients enrolled, 51% were female and the mean age was 66 ± 16 years. After PSM, a new cardiac complication or death within 30 days occurred in 5624 (33.1%) patients with CRP > 3 mg/L, in 4243 (25.6%) patients with CRP 1–3 mg/L and in 3891 (23.5%) patients with CRP 3 mg/L had higher risk of the composite outcome (HR 1.10, 95%CI 1.05–1.52; HR 1.51, 95%CI 1.45–1.58), death (HR 1.43, 95%CI 1.24–1.64; HR 3.50, 95%CI 3.01–3.96), HF (HR 1.08, 95%CI 1.01–1.16; HR 1.51, 95%CI 1.41–1.61), AF (HR 1.10, 95% CI:1.02–1.18; HR 1.42, 95%CI 1.33–1.52) and ventricular arrhythmias (HR 1.25, 95%CI 1.02–1.52; HR 1.67, 95% CI 1.38–2.01) compared to those with CRP 3 mg/L compared to those with CRP The role of inflammation in predicting early cardiac complications among stroke patients is unclear. Electronic medical records from TriNetX, a global federated health research network, were used for this retrospective analysis. Patients with ischemic stroke and C-Reactive Protein (CRP) levels measured within 24 h post-stroke were categorized into three groups: (i) < 1 mg/L, (ii)1–3 mg/L and (iii) > 3 mg/L. The primary outcome was a composite outcome of cardiac complications (heart failure (HF), ischemic heart disease, atrial fibrillation (AF), ventricular arrhythmias and Takotsubo cardiomyopathy) or death at 30 days from the index event. Cox-regression analyses were used to produce hazard ratios (HRs) and 95% confidence intervals (CI) following 1:1 propensity score matching (PSM). Of the 104,741 patients enrolled, 51% were female and the mean age was 66 ± 16 years. After PSM, a new cardiac complication or death within 30 days occurred in 5624 (33.1%) patients with CRP > 3 mg/L, in 4243 (25.6%) patients with CRP 1–3 mg/L and in 3891 (23.5%) patients with CRP < 1 mg/L. Patients with CRP levels of 1–3 mg/L and > 3 mg/L had higher risk of the composite outcome (HR 1.10, 95%CI 1.05–1.52; HR 1.51, 95%CI 1.45–1.58), death (HR 1.43, 95%CI 1.24–1.64; HR 3.50, 95%CI 3.01–3.96), HF (HR 1.08, 95%CI 1.01–1.16; HR 1.51, 95%CI 1.41–1.61), AF (HR 1.10, 95% CI:1.02–1.18; HR 1.42, 95%CI 1.33–1.52) and ventricular arrhythmias (HR 1.25, 95%CI 1.02–1.52; HR 1.67, 95% CI 1.38–2.01) compared to those with CRP < 1 mg/L. Ischemic heart disease were more common among patients with CRP levels > 3 mg/L compared to those with CRP < 1 mg/L (HR:1.33, 95% CI:1.26–1.40), while no association with Takotsubo cardiomyopathy was found in all the analyses. CRP levels within the first 24 h of an ischemic stroke predict 30-day cardiac complications or death.

The immune response to the SARS-CoV-2 infection is crucial to the patient outcome. IL-18 is involved in the lymphocyte response to the disease and it is well established its important role in the complex developing of the host response to viral infection. This study aims at the analysis of the concentrations of IL-18, IL-18BP, INF-γ at the onset of the SARS-CoV-2 infection. The serum levels of measured interleukins were obtained through enzyme-linked immunosorbent assay. Furthermore, the free fraction of IL-18 was numerically evaluated. The enrolled patients were divided in two severity groups according to a threshold value of 300 for the ratio of arterial partial pressure of oxygen and fraction of inspired oxygen fraction and according to the parenchymal involvement as evaluated by computerized tomography at the admittance. In the group of patients with a more severe disease, a significant increase of the IL-18, INF-γ and IL-18BP levels have been observed, whereas the free IL-18 component values were almost constant. The results confirm that, at the onset of the disease, the host response keep the inflammatory cytokines in an equilibrium and support the hypothesis to adopt the IL-18BP modulation as a possible and effective therapeutic approach.

Thrombosis associated with thrombocytopenia is an apparent paradox that is present across a wide spectrum of disorders. While thrombocytopenia has been a controversial clinical classification criterion for antiphospholipid syndrome because initial reports failed to demonstrate a relation between low platelet count with other clinical or laboratory manifestations of the syndrome, recent data highlight the association between mild to moderate thrombocytopaenia and the risk of thrombosis. Although antiphospholipid antibodies may induce platelet activation in vitro, additional stimuli may contribute to their activation in vivo, amongst which reactive oxygen and nitrogen species and lipid peroxidation products, elevated in patients with the antiphospholipid syndrome: an excess of the same stimuli may induce megakaryocyte and platelet apoptosis that leads to decreased platelet production and increased destruction, exposure resulting ultimately in thrombocytopaenia. Herein we provide a novel plausible framework involving free radicals that could add to the understanding of the thrombocytopenia/thrombosis paradox in the antiphospholipid syndrome.

To perform a systematic review and meta-analysis of studies reporting data on atherosclerosis and inflammatory markers in familial Mediterranean fever (FMF).EMBASE and PubMed databases were screened according to PRISMA guidelines from inception to January 2022 for articles reporting measurements of the intima media thickness (IMT) of carotid arteries and eventually carotid plaques; random effect meta-analyses for continuous outcomes and Peto's odds ratio for rare events were employed.The screening and selection search strategy yielded 18 case controls studies (16 full papers and 2 abstracts); the IMT was greater in FMF (n = 1112) than in controls (n = 901) (p 0.0001) with wide heterogeneity (IFMF is characterised by premature atherosclerosis expressed as a thicker intima media and a greater prevalence of carotid plaques, partially related to the C-reactive protein, as expected by the autoinflammatory nature of FMF. Key Points • Familial Mediterranean fever is characterised by premature atherosclerosis. • C-reactive protein relates to intima media thickness in keeping with the autoinflammatory nature Familial Mediterranean fever. • Targeting the inter-critical low-grade inflammation may be relevant to minimise the additional cardiovascular risk posed by premature atherosclerosis.

Aim To evaluate the clinical relevance of antiphospholipid antibodies (aPL) in patients with lower extremity peripheral artery disease (PAD). Data sources EMBASE and MEDLINE databases were searched from inception to March 2020 for clinical studies reporting on the association between of aPL [IgG/IgM anticardiolipin (aCL) and lupus anticoagulant (LA)] and PAD. Methods We determined the pooled prevalence (PP) of patients positive for aPL in PAD or the PP of PAD in patients positive for aPL; we employed Peto's odds ratio with random effect for the meta-analysis. Results Twenty-one studies comprising 6,057 patients were evaluated: in patients with PAD, the PP of IgG aCL was 12% vs 4.1% in those without, IgM aCL was 13.2% vs 2.1%, and LA 13.3% vs 3.3%, respectively. The PP of patients with LA was greater in critical limb ischemia than in the control group (19.3% vs 4.2%). Also, the PP of patients with LA was greater in the failed than in the successful revascularisation group (35.8% vs 15.8%). The PP of post-procedural revascularisation failures was similar in the groups given or not given oral anticoagulation (59.2% vs 61.9%). Conclusion All the aPL related to PAD regardless of diagnostic definition used, whereas LA related also to critical limb ischaemia and failed revascularisation. Data expressed as percentage of participants positive for aPL limit the interpretation of these relationships.

Background: Electrocardiogram (ECG) offers a valuable resource easily available in the emergency setting. Objective: Aim of the study was to describe ECG alterations on emergency department (ED) presentation or that developed during hospitalization in SARS-CoV-2-infected patients and their association with 28-day mortality. Methods: A retrospective, single-center study including hospitalized patients with SARS-CoV-2 was conducted. ECG was recorded on ED admission to determine: heart rhythm, rate, and cycle; atrio-ventricular and intra-ventricular conduction; right ventricular strain; and ventricular repolarization. A specialized cardiologist blinded for the outcomes performed all 12-lead ECG analyses and their interpretation. Results: 190 patients were included, with a total of 24 deaths (12.6%). Age (p < 0.0001) and comorbidity burden were significantly higher in non-survivors (p < 0.0001). Atrial fibrillation (AF) was more frequent in non-survivors (p < 0.0001), alongside a longer QTc interval (p = 0.0002), a lower Tp-e/QTc ratio (p = 0.0003), and right ventricular strain (p = 0.013). Remdesivir administration was associated with bradycardia development (p = 0.0005) but no increase in mortality rates. In a Cox regression model, AF (aHR 3.02 (95% CI 1.03–8.81); p = 0.042), QTc interval above 451 ms (aHR 3.24 (95% CI 1.09–9.62); p = 0.033), and right ventricular strain (aHR 2.94 (95% CI 1.01–8.55); p = 0.047) were associated with higher 28-day mortality risk. Conclusions: QTc interval > 451 ms, right ventricular strain, and AF are associated with higher mortality risk in SARS-CoV-2 hospitalized patients. ECG recording and its appropriate analysis offers a simple, quick, non-expensive, and validated approach in the emergency setting to guide COVID-19 patients’ stratification.

The proprotein convertase subtilisin/kexin type 9 (PCSK9) is emerging as a novel cardiovascular risk factor. Levels of PCSK9 in thrombotic primary antiphospholipid syndrome (PAPS) have never been investigated.Cross sectional comparison of baseline characteristics of 91 PAPS patients enrolled in the multicenter prospective ATHERO-APS cohort study. PCSK9 levels were categorized into tertiles and the association with arterial and recurrent thrombosis were assessed by univariable and multivariable logistic regression analysis.Median age was 51 years and 71.4% (n = 65) were women. Overall, 33% (n = 30) experienced an arterial event while 31% (n = 28) had recurrent thrombotic events. Median PCSK9 levels were 1243 (1100-1650) pg/ml. Patients in the third PCSK9 tertile (1458 pg/ml) showed a higher prevalence of dyslipidemia, lupus anticoagulant positivity and a history of previous arterial and recurrent thrombosis than patients in the first and second tertile. PCSK9 levels were higher in arterial than venous thrombosis (1502 vs. 1180 pg/ml, p = 0.002), and in patients with recurrent vs isolated thrombosis (1680 vs. 1150 pg/m, p 0.001). High plasma PCSK9 levels were associated with a 4-fold increase risk for arterial events and with a 10-fold increase risk for recurrent thrombosis after adjustment for confounding factors.These preliminary data suggest that PCSK9 levels are increased in PAPS patients with arterial and recurrent thrombosis. Its role as a possible therapeutic target in PAPS needs further studies.

Liver damage worsens the prognosis of coronavirus 19 disease (COVID-19). However, the best strategy to stratify mortality risk according to liver damage has not been established. The aim of this study is to test the predictive value of the validated Fibrosis-4 (FIB-4) Index and compared it to liver transaminases and to the AST-to-Platelet ratio index (APRI). Multicenter cohort study including 992 consecutive COVID-19 patients admitted to the Emergency Department. FIB-4 3.25 and APRI 0.7 were used to define liver damage. Multivariable Cox regression and ROC curve analysis for mortality were performed. Secondary endpoints were (1) need for high-flow oxygen and (2) mechanical ventilation. 240 (24.2%) patients had a FIB-4 3.25. FIB-4 3.25 associated with an increased mortality (n = 119, log-rank test p 0.001 and adjusted hazard ratio (HR) 1.72 (95% confidence interval [95%CI] 1.14-2.59, p = 0.010). ROC analysis for mortality showed that FIB-4 (AUC 0.734, 95% CI 0.705-0.761) had a higher predictive value than AST (p = 0.0018) and ALT (p 0.0001). FIB-4 3.25 was also superior to APRI 0.7 (AUC 0.58, 95% CI 0.553-0.615, p = 0.0008). Using an optimized cut-off 2.76 (AUC 0.689, 95% CI 0.659-0.718, p 0.0001), FIB-4 was superior to FIB-4 3.25 (p = 0.0302), APRI 0.7 (p 0.0001), AST 51 (p = 0.0119) and ALT 42 (p 0.0001). FIB-4 was also associated with high-flow oxygen use (n = 255, HR 1.69, 95% CI 1.25-2.28, p = 0.001) and mechanical ventilation (n = 39, HR 2.07, 95% CI 1.03-4.19, p = 0.043). FIB-4 score predicts mortality better than liver transaminases and APRI score. FIB-4 score may be an easy tool to identify COVID-19 patients at worse prognosis in the emergency department.

Aim To evaluate the relevance of plasma homocysteine (HC) in Behcet's disease (BD) and its clinical manifestations. Methods Systematic review of EMBASE and PubMed databases according to PRISMA guidelines from inception to July 2021; random-effects meta-analyses for continuous outcomes. Results The search strategy retrieved 48 case–control (2,669 BD and 2,245 control participants) and 5 cohort studies (708 BD participants). Plasma HC was higher in BD than in controls (p 1.5; some pooled ethnicities explained a small part of the heterogeneity (I2 = 16.3%). Active BD participants had higher HC than inactive ones (p Conclusion Although causality cannot be inferred, the consistency of the elevation of plasma HC in BD, particularly in patients with active disease, with vascular and ocular involvement suggests an intrinsic involvement of HC in these clinical manifestations.

Beyond well-assessed risk factors, cardiovascular events could be also associated with the presence of epigenetic and genetic alterations, such as the methylenetetrahydrofolate-reductase (MTHFR) C677T polymorphism. This gene variant is related to increased circulating levels of homocysteine (Hcy) and cardiovascular risk. However, heterozygous carriers have an augmented risk of cardiovascular accidents independently from normal Hcy levels, suggesting the presence of additional deregulated processes in MTHFR C677T carriers. Here, we hypothesize that targeting Sirtuin 1 (SIRT1) could be an alternative mechanism to control the cardiovascular risk associated to MTHFR deficiency condition. Flow Mediated Dilatation (FMD) and light transmission aggregometry assay were performed in subjects carrying MTHFR C677T allele after administration of resveratrol, the most powerful natural clinical usable compound that owns SIRT1 activating properties. MTHFR C677T carriers with normal Hcy levels revealed endothelial dysfunction and enhanced platelet aggregation associated with SIRT1 downregulation. SIRT1 activity stimulation by resveratrol intake was able to override these abnormalities without affecting Hcy levels. Impaired endothelial function, bleeding time, and wire-induced thrombus formation were rescued in a heterozygous Mthfr-deficient (Mthfr+/–) mouse model after resveratrol treatment. Using a cell-based high-throughput multiplexed screening (HTS) assay, a novel selective synthetic SIRT1 activator, namely ISIDE11, was identified. Ex vivo and in vivo treatment of Mthfr+/– mice with ISIDE11 rescues endothelial vasorelaxation and reduces wire-induced thrombus formation, effects that were abolished by SIRT1 inhibitor. Moreover, platelets from MTHFR C677T allele carriers treated with ISIDE11 showed normalization of their typical hyper-reactivity. These results candidate SIRT1 activation as a new therapeutic strategy to contain cardio and cerebrovascular events in MTHFR carriers.

Patients with primary antiphospholipid syndrome (PAPS) may suffer from venous and/or arterial thrombosis, but studies addressing eventual clinical and laboratory features that may discriminate between arterial thromboembolism (ATE) from venous thromboembolism (VTE) have been poorly addressed.Cross sectional comparison of baseline characteristics of 100 patients enrolled in the multi center ATHERO-APS cohort study; patients with previous ATE and VTE were compared with regards to clinical and biochemical variables as well as to echocardiographic features and ankle-brachial index (ABI) measured at enrolment.Mean age of patients was 51 years, 72 were women. 60 patients suffered VTE and 40 ATE. Compared to VTE, ATE patients displayed a higher prevalence of hypertension (43.3% vs. 65%, p = 0.034) and diabetes (3.3% vs. 17.5%, p = 0.015). Mean concentration of inflammation and complement activation markers were similar between the two groups as well as autoantibodies titres; mean D-dimer concentration was greater in VTE patients (184 ng/ml vs. 347 ng/ml; p = 0.024) whereas mean platelet count was greater in ATE patients (263 × 10Clinical, laboratory and cardiovascular variables distinguish arterial from venous APS patients, amongst which the ABI and left atrial enlargement. Implications for these two distinct clinical phenotypes of APS patients need further investigation.

Background The prevalence of heart failure with preserved ejection fraction (HFpEF) in patients with antiphospholipid syndrome (APS) is unknown. Methods Prospective multicenter cohort study including 125 patients: 91 primary APS (PAPS), 18 APS-SLE, and 16 carriers. HFpEF was diagnosed according to the 2019 European Society of Cardiology criteria: patients with ≥5 points among major and minor functional and morphological criteria including NT-ProBNP >220 pg/ml, left atrial (LA) enlargement, increased left ventricular filling pressure. Results Overall, 18 (14.4%) patients were diagnosed with HFpEF; this prevalence increased from 6.3% in carriers to 13.2% in PAPS and 27.8% in APS-SLE (Figure). Patients with HFpEF were older and with a higher prevalence of hypertension and previous arterial events. At logistic regression analysis, age, arterial hypertension, anticardiolipin antibodies IgG >40 GPL (odds ratio [OR] 3.43, 95% Confidence Interval [CI] 1.09–10.77, p=0.035), anti β-2-glycoprotein-I IgG >40 GPL (OR 5.28, 1.53–18.27, p=0.009), lupus anticoagulants DRVVT >1.25 (OR 5.20, 95% CI 1.10–24.68, p=0.038), (OR 3.56, 95% CI 1.11–11.47, p=0.033) and triple positivity (OR 3.56, 95% CI 1.11–11.47, p=0.033) were associated with HFpEF after adjustment for age and sex. Discussion HFpEF has a clinically relevant prevalence in patients with APS. The role of antiphospholipid antibodies in the pathogenesis and prognosis of HFpEF needs to be investigated. Funding Acknowledgement Type of funding sources: None.

Objectives: COVID-19 may show no peculiar signs and symptoms that may differentiate it from other infective or non-infective etiologies, thus, early recognition and prompt management are crucial to improve survival. The aim of this study was to describe clinical, laboratory, and radiological characteristics and outcomes of hospitalized COVID-19 patients compared to those with other infective or non-infective etiologies. Methods: We performed a prospective study from March 2020 to February 2021. All patients hospitalized for suspected or confirmed COVID-19 were prospectively recruited. All patients were evaluated according to a predefined protocol for diagnosis of suspected SARS-CoV-2 infection. The primary endpoint was evaluation of clinical, laboratory, and radiological characteristics associated or not with COVID-19 etiology at time of hospitalization in an emergency department. Results: A total of 1036 patients were included in the study: 717 (69%) patients with confirmed COVID-19 and 319 (31%) without COVID-19, hospitalized for other causes. The main causes of hospitalization among non-COVID-19 patients were acute heart failure (44%) and bacterial pneumonia (45.8%). Overall, 30-day mortality was 9% among the COVID-19 group and 35% in the non-COVID-19 group. Multivariate analysis showed variables (fever &gt, 3 days, dry cough, acute dyspnea, lymphocytes &lt, 1000 × 103/µL, and ferritin &gt, 250 ng/mL) independently associated with COVID-19 etiology. A decision tree was elaborated to early detect COVID-19 patients in the emergency department. Finally, Kaplan–Meier curves on 30-day survival in COVID-19 patients during the first wave (March–May 2020, n = 289 patients) and the second wave (October–February 2021, n = 428 patients) showed differences between the two study periods (p = 0.021). Conclusions: Patients with confirmed diagnosis of COVID-19 may show peculiar characteristics at time of hospitalization that could help physicians to distinguish from other infective or non-infective etiologies. Finally, a different 30-day mortality rate was observed during different periods of the pandemic.

Mastocytosis is a rare disease characterized by clonal proliferation of mast cells (MCs) in different organs. Clinical manifestations of mastocytosis are mostly due to release of mediators from MCs and, in many cases, such as urticaria, flushing, angioedema, and anaphylaxis, are an expression of the biological effects of mediators on endothelial cells. Chronic secretion of mediators in patients with mastocytosis can lead to alteration of endothelial function.We sought to investigate endothelial function in patients with mastocytosis using a noninvasive technique of flow-mediated dilation (FMD).Twenty-five adult patients with indolent and advanced forms of mastocytosis and 20 healthy control subjects were enrolled in the study. Ultrasound assessment of FMD was performed by measuring changes in the diameter of the brachial artery after 5 minutes of arterial occlusion. Changes in FMD were correlated with clinical parameters and serum tryptase levels.Patients with mastocytosis had lower FMD compared with healthy control subjects (P .001). Advanced and smoldering forms showed a lower FMD compared with indolent forms (P .001). FMD inversely correlated with age and serum tryptase levels and directly with median arterial pressure and recurrent flushing episodes. No correlation was found between FMD and osteoporosis, recurrent anaphylaxis, presence of skin lesions, and long-term antihistamine treatment.Endothelial dysfunction, as demonstrated by FMD reduction, is detectable in patients with mastocytosis and is more severe in patients with high tryptase levels and advanced disease. Endothelial function appears to be negatively influenced by MC proliferation rather than by the severity of mediator-related symptoms.

Background Patients with non valvular atrial fibrillation (AF) and cancer represent a high-risk subgroup of patients in whom the management of oral anticoagulation may be challenging. The relationship between cancer type and the risk of cardiovascular events (CVEs) in patients with AF is unclear. Purpose To investigate the incidence of CVEs in patients with AF and cancer according to cancer type. Methods Prospective cohort study including 2,092 consecutive AF patients on vitamin K antagonists. Principal endpoint was the occurrence of CVEs including fatal/non-fatal myocardial infarction and ischemic stroke and cardiovascular death. We also performed a subgroup analysis of cardiac and thromboembolic events separately. Patients with cancer were divided in subgroups based on cancer site as follows: group 1 gastrointestinal tract; group 2 respiratory tract; group 3 genitourinary tract; group 4 other sites. Results Mean age was 73.7±9.1 years and 42.1% were woman; 367 (17.5%) had cancer, of these 21% gastro-intestinal, 10% respiratory, 28% genito-urinary and 41% had other localization. Patients with cancer were older than those without but with similar clinical characteristics. During a mean follow up of 35.9±28.0 months (6264.5 patient-years), 203 CVEs occurred (3.24%/year, 95% CI 2.81–3.72) of whom 86 were cardiac ischemia (1.37%/year, 95% CI 1.10–1.69), 70 thromboembolic events (1.12%/year, 95% CI 0.87–1.41) and 47 cardiovascular deaths (0.75%/year, 95% CI 0.55–0.99). The incidence of CVEs for AF patients with and without cancer was respectively (n=45, 3.78%, 95% CI 2.76–5.06) and (n=158, 3.11%/year, 95% CI 2.65–3.64). In particular, compared to patients without cancer, a higher incidence rate of CVEs was found in patients with gastrointestinal tract cancer (5.61%/year, 95% CI 2.90–9.79, p=0.046), and in patients with respiratory tract cancer (6.15%/year, 95% CI 2.66–12.1, p=0.055), while no difference was found in patients with genito-urinary tract cancer (2.24%/year, 95% CI 0.97–4.41, p=0.362) and other site cancer (3.11%/year, 95% CI 2.65–3.64, p=0.512). Cox regression multivariate analysis showed that factors associated with cardiac events were COPD, dyslipidemia, TTR Conclusions Our findings suggest an association between cancer type and specific ischemic complications in AF patients. In particular, we found a higher risk of cardiac complications in patients with gastrointestinal cancer and of thromboembolic events in patients with respiratory cancer. These associations need to be confirmed in larger studies. Funding Acknowledgement Type of funding source: None

Background: To investigate the association between family history of atrial fibrillation (AF) with cardiovascular events (CVEs), major adverse cardiac events (MACE), and cardiovascular mortality. Methods: Multicenter prospective observational cohort study including 1722 nonvalvular AF patients from February 2008 to August 2019 in Italy. Family history of AF was defined as the presence of AF in a first-degree relative: mother, father, sibling, or children. Primary outcome was a composite of CVEs including fatal/nonfatal ischemic stroke and myocardial infarction, and cardiovascular death. Second, we analyzed the association with major adverse cardiac event. Results: Mean age was 74.6±9.4 years; 44% of women. Family history of AF was detected in 368 (21.4%) patients, and 3.5% had ≥2 relatives affected by AF. Age of AF onset progressively decreased from patients without family history of AF, compared with those with single and multiple first-degree affected relatives ( P P =0.039), major adverse cardiac event (hazard ratio, 1.917 [95% CI, 1.207–3.045], P =0.006), and cardiovascular mortality (hazard ratio, 2.008 [95% CI, 1.047–3.851], P =0.036). Subgroup analysis showed that this association was modified by age, sex, and prior ischemic heart disease. Conclusions: In a cohort of elderly patients with a high atherosclerotic burden, family history of AF is evident in >20% of patients and was associated with an increased risk for CVEs and mortality. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01882114.

INTRODUCTION The relationship between autoimmune hemolytic anemia and antiphospholipid antibodies (aPL) and/or antiphospholipid syndrome has never been systematically addressed. METHODS Systematic review of EMBASE and PubMed databases performed according to PRISMA guidelines from inception to March 2020; meta-analysis performed by Peto's odds ratio for rare events. FINDINGS Forty-five studies with different outcomes met the inclusion/exclusion criteria. The pooled prevalence (PP) of IgG anticardiolipin antibodies (aCL) positivity was greater in end-stage renal disease (ESRD) than controls (20.2% vs. 2.6%, P = 0.001, I2 >80%; I2 = heterogeneity), particularly in hemodialysis patients (18.3% vs. 8%, I2 = 0%). The PP of lupus anticoagulant was greater in ESRD than controls (8.7% vs. 0.2%, P

Severe anaphylaxis is a generalized reaction in which cardiovascular and respiratory involvement lead to a fatal or near-fatal outcome. Triggers of severe anaphylaxis differ from one age group to another and are mostly represented by drugs and hymenoptera stings in adults and food in children. Several risk factors and cofactors can increase the odds of severe anaphylaxis by different and still undefined mechanisms. Major risk factors for severe anaphylaxis include old age, male sex, and preexisting medical conditions such as mast cell disorders, cardiovascular diseases, and uncontrolled asthma. Antihypertensive drugs appear to increase the severity of anaphylaxis probably by impairing compensatory mechanism to support blood pressure during the reaction. Severe reactions are also associated with transient cofactors such as exercise following specific allergen exposure, treatment with nonsteroidal anti-inflammatory drugs, and alcohol consumption. Identification of risk factors and potential concurrent cofactors for each individual patient is mandatory to prevent severe anaphylaxis. Risk stratification is crucial to develop personalized prevention strategies and action plans to avoid potentially life-threatening reactions.

Background. The prevalence of heart failure with preserved ejection fraction (HFpEF) in patients with antiphospholipid syndrome (APS) is unknown. Methods. A prospective multicenter cohort study including 125 patients was conducted: 91 primary APS (PAPS), 18 APS-SLE, and 16 carriers. HFpEF was diagnosed according to the 2019 European Society of Cardiology criteria: patients with ≥5 points among major and minor functional and morphological criteria including NT-ProBNP &gt, 220 pg/mL, left atrial (LA) enlargement, increased left ventricular filling pressure. Results. Overall, 18 (14.4%) patients were diagnosed with HFpEF, this prevalence increased from 6.3% in carriers to 13.2% in PAPS and 27.8% in APS-SLE. Patients with HFpEF were older and with a higher prevalence of hypertension and previous arterial events. At logistic regression analysis, age, arterial hypertension, anticardiolipin antibodies IgG &gt, 40 GPL (odds ratio (OR) 3.43, 95% confidence interval (CI) 1.09–10.77, p = 0.035), anti β-2-glycoprotein-I IgG &gt, 40 GPL (OR 5.28, 1.53–18.27, p = 0.009), lupus anticoagulants DRVVT &gt, 1.25 (OR 5.20, 95% CI 1.10–24.68, p = 0.038), and triple positivity (OR 3.56, 95% CI 1.11–11.47, p = 0.033) were associated with HFpEF after adjustment for age and sex. By multivariate analysis, hypertension (OR 19.49, 95% CI 2.21–171.94, p = 0.008), age (OR 1.07, 95% CI 1.00–1.14, p = 0.044), and aβ2GPI IgG &gt, 40 GPL (OR 8.62, 95% CI 1.23–60.44, p = 0.030) were associated with HFpEF. Conclusion. HFpEF is detectable in a relevant proportion of APS patients. The role of aPL in the pathogenesis and prognosis of HFpEF needs further investigation.

Community-acquired pneumonia (CAP) is complicated by cardiovascular events as myocardial infarction and stroke but the underlying mechanism is still unclear. We hypothesized that endothelial dysfunction may be implicated and that endotoxemia may have a role.Fifty patients with CAP and 50 controls were enrolled. At admission and at discharge, flow-mediated dilation (FMD), serum levels of endotoxins and oxidative stress, as assessed by serum levels of nitrite/nitrate (NOx) and isoprostanes, were studied.At admission, a significant difference between patients with CAP and controls was observed for FMD (2.1±0.3 vs 4.0±0.3%, p0.001), serum endotoxins (157.8±7.6 vs 33.1±4.8pg/ml), serum isoprostanes (341±14 vs 286±10 pM, p=0.009) and NOx (24.3±1.1 vs 29.7±2.2μM). Simple linear correlation analysis showed that serum endotoxins significantly correlated with Pneumonia Severity Index score (Rs=0.386, p=0.006). Compared to baseline, at discharge CAP patients showed a significant increase of FMD and NOx (from 2.1±0.3 to 4.6±0.4%, p0.001 and from 24.3±1.1 to 31.1±1.5μM, p0.001, respectively) and a significant decrease of serum endotoxins and isoprostanes (from 157.8±7.6 to 55.5±2.3pg/ml, p0.001, and from 341±14 to 312±14 pM, p0.001, respectively). Conversely, no changes for FMD, NOx, serum endotoxins and isoprostanes were observed in controls between baseline and discharge. Changes of FMD significantly correlated with changes of serum endotoxins (Rs=-0.315; p=0.001).The study provides the first evidence that CAP is characterized by impaired FMD with a mechanism potentially involving endotoxin production and oxidative stress.

Antiphospholipid antibodies (aPL) are well-known risk factors for venous and arterial thrombosis, but their association with cognitive dysfunction has not been widely investigated in the general population and in patients with primary and secondary antiphospholipid syndrome (APS). We performed a systematic review searching MEDLINE via PubMed and Cochrane (CENTRAL) databases for observational studies reporting on the association between aPL and dementia in the general population, in subjects carrying aPL, in patients with cognitive disorder/dementia, and in primary and secondary APS. Prevalence of anticardiolipin (aCL) IgG ranged from 5.9% to 31.1% in the general population, with aCL titers being more elevated in subjects with functional decline of cognitive functions or with neurological alterations as detected by imaging. The prevalence of aPL ranged from 6.0 to 56.6% in patients with vascular dementia. Regarding patients with primary and secondary APS, a severe cognitive deficit has been described in up to 60% of patients, 33.3% of systemic lupus erythematosus (SLE)-APS and 22.2% of SLE patients without aPL. Five studies included patients with primary APS with divergent results, while 18 studies investigated the association between aPL and cognitive impairment in patients with SLE. Of these, 14 reported a positive association between aPL, mostly aCL and LAC, and cognitive impairment while little evidence on anti β2-Glycoprotein I exists. Mechanisms leading to cognitive dysfunction are not well characterized and may include vascular aPL-induced micro and macro-thrombosis and immune-mediated neuronal toxicity pathways in the cerebral district.

Anticardiolipin antibodies of the immunoglobulin G isotype (IgG aCL) have been suggested as risk factor for arterial and venous thrombosis. No conclusive data in patients with coronary artery disease (CAD) do exist. We investigate the risk of recurrent CAD according to the presence of IgG aCL.We performed a systematic review and meta-analysis to evaluate the risk of recurrent major adverse cardiac events (MACE) associated with the presence of IgG aCL in patients with CAD. MEDLINE and Cochrane databases were searched. We conducted a meta-analysis of the relative risk (RR) both at 12 and 24 months.We included 11 eligible studies with a total of 2425 patients, 283 IgG aCL+ and 2142 IgG aCL-. The prevalence of IgG aCL+ ranged from 6.1% to 43.3%. A total of 341 cardiac events were reported: 71 (25.1%) in IgG aCL+ and 270 (12.6%) in IgG aCL- patients. We found an increased risk of recurrent MACE in patients with high IgG aCL both at 12 (RR 2.17, 2.5-97.5%CI, 1.54-3.00) and 24 months (RR 2.11, 2.5-97.5%CI, 1.62-2.66). This association was even stronger in patients with juvenile CAD (i.e.50 years) at both 12 (RR 3.21, 2.5-97.5%CI, 1.74-5.41) and 24 months (RR 3.24, 2.5-97.5%CI, 1.84-5.21).Patients with CAD and elevated IgG aCL have a doubled risk of recurrent MACE at 12 and 24 months. The presence of aCL should be suspected in patients with recurrent CAD events or in patients with juvenile CAD.

Prothrombin fragment F1 + 2 (F1 + 2) and thrombin–antithrombin (TAT) have been assessed in antiphospholipid syndrome (APS) but without evaluating a direct relationship with antiphospholipid (aPL) antibody titers. This article aims to investigate a direct relationship between aPL and F1 + 2 and perform a systematic review and meta-analysis of F1 + 2 and TAT in APS. Systematic search was performed using EMBASE and PubMed databases from January 1982 to December 2018 and random effects meta-analyses for continuous outcomes. This is a cross-sectional case–control study; immunoglobulin G/immunoglobulin M (IgG/IgM) anticardiolipin (aCL) anti-β2-glycoprotein-I, antiprothrombin (aPT) antibodies, F1 + 2, and lupus anticoagulants (LA) were measured in 25 thrombotic primary APS (PAPS), 9 nonthrombotic carriers of aPL, and 18 controls. The significant effect size (ES) for F1 + 2 between aPL +ve and aPL −ve systemic lupus erythematosus (SLE) and between aPL +ve SLE and control displayed high heterogeneity. The significant ES for F1 + 2 between aPL −ve SLE and controls displayed no heterogeneity. The ES for TAT between aPL +ve and aPL −ve SLE patients and between aPL −ve SLE and controls was low, without heterogeneity. Mean F1 + 2 was greater in PAPS (p

To evaluate the effect of antiphospholipid antibodies (aPL) on renal allograft outcome after kidney transplantation.A systematic search of EMBASE and PubMed databases from inception to July 2018 was run according to PRISMA guidelines; Peto's odds ratio (OR) for rare events was used for the meta-analysis.Our inclusion/exclusion criteria were met by 22 cohort studies having different outcomes: allograft thrombosis (n = 9) and thromboprophylaxis (n = 3), allograft loss from any cause (n = 9), allograft malfunction (n = 3), duration (n = 2), glomerular filtration rate at 1 year (n = 3) and allograft rejection (n = 5). The pooled prevalence of allograft thrombosis and of thrombotic microangiopathy was greater in aPL+ve than negative recipients (10.4% vs 1.7%, p 0.0001 and 10.2% vs 0%, p = 0.005, respectively). The pooled prevalence of allograft thrombosis was 75% in patients not taking anticoagulation whereas none of the anticoagulated recipients developed thrombosis (p 0.0001). The pooled prevalence of allograft loss was greater in aPL+ve recipients (28% vs 18% respectively, p 0.0001); the pooled prevalence of aPL was greater in allograft loss recipients compared to those who did not lose it (51% vs 33%, p 0.0001). The pooled prevalence of allograft malfunction and rejection was similar in aPL-ve and aPL+ve recipients (32.2% vs 40.3% and 14.9% vs 14.4%, respectively) but graft duration was shorter in aPL+ve than aPL-ve recipients (p = 0.001) and glomerular filtration rate at 1 year was lower in aPL + ve than aPL-ve recipients (p 0.0001).APL relate strongly to allograft thrombosis, loss and duration but not to allograft malfunction and rejection. Oral antivitamin K anticoagulants effectively prevent allograft thrombosis in aPL recipients. The debate on the role of aPL in renal transplant is limited by the expression of data as percentage of recipients positive for aPL rather than aPL titres in many studies.

To further the knowledge of oxidative stress in systemic sclerosis (SSc), we performed a systematic review and meta-analysis on studies measuring isoprostane, a vasoactive agent deriving from arachidonic acid and implicated in the vasculopathy of SSc.Systematic search following the PRISMA guidelines in PubMed and EMBASE between January-1990/December-2017 using the terms: oxidative stress, isoprostane, systemic sclerosis and scleroderma.After the screening process, 8 studies including 240 SSc patients and 192 controls were included in the systematic review and meta-analysis, 6 investigating urinary and 2 serum isoprostane: random effect meta-analysis revealed isoprostane overgeneration in SSc (p .001) with wide heterogeneity (IThere is some evidence for isoprostane overgeneration in SSc that confirms the occurrence of oxidative stress in this setting: further prospective studies with specified outcomes are needed to evaluate the prognostic value of this functional biomarker.

Systemic sclerosis (SSc) is a multisystem autoimmune disease: characterised from the clinical side by progressive vasculopathy and fibrosis of the skin and different organs and from the biochemical side by fibroblast deregulation with excessive production of collagen and increased expression of nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4). The latter contributes to an overproduction of reactive oxygen species that through an autocrine loop maintains NOX4 in a state of activation. Reactive oxygen and nitrogen species are implicated in the origin and perpetuation of several clinical manifestations of SSc having vascular damage in common; attempts to dampen oxidative and nitrative stress through different agents with antioxidant properties have not translated into a sustained clinical benefit. Objective of this narrative review is to describe the origin and clinical implications of oxidative and nitrative stress in SSc, with particular focus on the central role of NOX4 and its interactions, to re-evaluate the antioxidant approaches so far used to limit disease progression, to appraise the complexity of antioxidant treatment and to touch on novel pathways elements of which may represent specific treatment targets in the not so distant future. info:eu-repo/semantics/publishedVersion

Background NAFLD is associated to Insulin Resistance (IR). IR is responsible for Endothelial Dysfunction (ED) through the impairment of eNOS function. Although eNOS derangement has been demonstrated in experimental models, no studies have directly shown that eNOS dysfunction is associated with NAFLD in humans. The aim of this study is to investigate eNOS function in NAFLD patients. Methods Fifty-four NAFLD patients were consecutively enrolled. All patients underwent clinical and laboratory evaluation and liver biopsy. Patients were divided into two groups by the presence of NAFL or NASH. We measured vascular reactivity induced by patients’ platelets on isolated mice aorta rings. Immunoblot assays for platelet-derived phosphorylated-eNOS (p-eNOS) and immunohistochemistry for hepatic p-eNOS have been performed to evaluate eNOS function in platelets and liver specimens. Flow-mediated-dilation (FMD) was also performed. Data were compared with healthy controls. Results Twenty-one (38, 8%) patients had NAFL and 33 (61, 7%) NASH. No differences were found between groups and controls except for HOMA and insulin (p

Platelet activation plays a major role in cardiovascular events (CVEs). Mediterranean diet (Med-Diet) reduces the incidence of stroke and myocardial infarction but it is still unclear if it affects platelet activation. Aim of the study was to evaluate the effect of Med-Diet on the urinary excretion of 11-dehydro-thromboxane (Tx) B2, a marker of in vivo platelet activation, in patients with atrial fibrillation (AF).Prospective observational cohort study including 801 non-valvular AF patients on chronic treatment with warfarin/acenocumarol referring to I Medical Clinic - Atherothrombosis Center of Sapienza University of Rome, Italy, from February 2008 to December 2013. Adherence to Med-Diet was evaluated by a short nine-items dietary questionnaire. Urinary excretion of 11-dehydro-TxB2 was measured in all patients.Mean follow-up was 33.9 (±19.8) months, yielding 2223 patient/year of observation. Mean age of patients was 73.3 (±8.9) years, 43.7% were female. Median value of urinary TxB2 was 105.5 [60.0-190.0] ng/mg creatinine. We found a significant inverse correlation between total Med-Diet score and 11-dehydro-TxB2 values (Rs: -0.356, p0.001). In a multivariable stepwise linear regression analysis, history of stroke/TIA (β = 0.146, p = 0.003), olive oil (β = -0.130, p = 0.007), wine (β = -0.102, p = 0.036) and antiplatelet drugs (β = -0.098, p = 0.045) were independently associated to 11-dehydro-TxB2. We found no differences in the rate of ischemic or bleeding events across tertiles of Med-Diet score during follow-up.Med-Diet adherence is inversely associated to urinary excretion of 11-dehydro-TxB2, suggesting that Med-Diet may favorably affect platelet function in AF patients. Clinical Trial Registration: ClinicalTrials.gov NCT01882114.

BACKGROUND Recent findings suggest that patients with atrial fibrillation (AF), in addition being at thromboembolic risk, are at risk of myocardial infarction (MI). Our aim was to investigate predictors of MI and cardiovascular death in a cohort of patients with AF who were taking anticoagulants. METHODS We prospectively followed up 1,019 patients with AF for a median of 33.7 months (3,223 person-years). All patients were treated with oral vitamin K antagonists. Primary outcome was a composite end point of cardiovascular events (CVEs) including fatal/nonfatal MI, cardiac revascularization, and cardiovascular death. RESULTS The mean age of the patients was 73.2 years, and 43.8' were women. At follow-up, 111 CVEs (3.43'/y) had occurred: 47 fatal-nonfatal MI/revascularization and 64 cardiovascular deaths. In addition, 31 stroke/transient ischemic attacks (0.96'/y) were recorded. Patients experiencing CVEs were older ( P P = .005), heart failure ( P = .001), and prior cardiac ( P P P P = .011), history of cerebrovascular (HR, 1.704; 95' CI, 1.119-2.597; P = .013) and cardiac (HR, 1.658; 95' CI, 1.105-2.489; P = .015) events, MetS (HR, 1.663; 95' CI, 1.107-2.499; P = .014), heart failure (HR, 1.584; 95' CI, 1.021-2.456; P = .040), and male sex (HR, 1.499; 95' CI, 1.010-2.223; P = .044) predicted CVEs. CONCLUSIONS Patients with AF still experience a high rate of CVEs despite receiving anticoagulant treatment. MetS is a common clinical feature in patients with AF, which increases the risk of CVEs. A holistic approach is needed to reduce the cardiovascular risk in patients with AF. TRIAL REGISTRY ClinicalTrials.gov ; No.: NCT01882114; URL: www.clinicaltrials.gov

Some evidences suggest that the use of digoxin may be harmful inatrial fibrillation (AF) patients. The aim of the study was to investigate in a "real world" of AF patients receiving vitamin K antagonists (VKAs), the relationship between digoxin use and mortality.Prospective single-center observational study including 815 consecutive non-valvular AF patients treated with VKAs. Total mortality was the primary outcome of the study. We also performed a sub-analysis considering only cardiovascular (CV) deaths. Time in therapeutic range (TTR) was used for anticoagulation quality.Median follow-up was 33.2months (2460 person-years); 171 (21.0%) patients were taking digoxin. Compared to those without, patients on digoxin were older (p=0.007), with a clinical history of HF (p0.001) and at higher risk of thromboembolic events (p0.001). No difference in TTR between the two groups was registered (p=0.598). During the follow-up, 85 deaths occurred: 47 CV and 38 non-CV deaths; 35 deaths occurred in digoxin users (20.6%). A significant increased rate of total mortality was observed in digoxin-treated patients (p0.001). Multivariable analysis showed that digoxin was associated with total mortality (hazard ratio [HR]: 2.224, p0.001) and CV death (HR: 4.686, p0.001). A propensity score-matched analysis confirmed that digoxin was associated with total mortality (HR: 2.073, p=0.0263) and CV death (HR: 4.043, p=0.004).In AF patients on good anticoagulation control with VKAs, digoxin use was associated with a higher rate of total and CV mortality.

Background and aims Blood lysosomal acid lipase (LAL) is reduced in non-alcoholic steatohepatitis, which is the major cause of cryptogenic cirrhosis (CC); few data on LAL activity in CC do exist. We investigated LAL activity in a cohort of patients with liver cirrhosis. Methods This is a multicentre cohort study including 274 patients with liver cirrhosis of different aetiology from 19 centres of Internal Medicine, Gastroenterology and Hepatology distributed throughout Italy. Blood LAL activity (nmol/spot/h) was measured with dried blood spot extracts using Lalistat 2. Results Overall, 133 patients had CC, and 141 patients had cirrhosis by other causes (61 viral, 53 alcoholic, 20 alcoholic + viral, 7 autoimmune). Mean age was 64.2 ± 13.4 years, and 28.5% were women. Patients with CC were older compared to other aetiology-cirrhosis, with a lower Child-Turcotte-Pugh (CTP, p=0.003) and MELD (p=0.009) score, and a higher prevalence of cardio-metabolic risk factors and previous ischemic events. In the whole cohort, median LAL activity value was 0.58 nmol/spot/h, 0.49 and 0.65 in the groups of CC and known-aetiology cirrhosis, respectively (p=0.002). The difference remained significant after adjustment for white blood cells count (p=0.001). Multivariable linear regression analysis showed that CC (vs. known aetiology, Beta = −0.144, p=0.018), platelet count (Beta = 0.398, p < 0.001) and CTP score (Beta = −0.133, p=0.022) were associated with log-LAL activity. Similar results were found using MELD as covariate. Conclusions We found a marked reduction of LAL activity in patients with cryptogenic cirrhosis compared to the other known aetiologies. A prospective study will clarify the role of LAL in chronic liver diseases.

Background: NAFLD is associated to Insulin Resistance (IR). IR is responsible for Endothelial Dysfunction (ED) through the impairment of eNOS function. Although eNOS derangement has been demonstrated in experimental models, no studies have directly shown that eNOS dysfunction is associated with NAFLD in humans. The aim of this study is to investigate eNOS function in NAFLD patients.Methods: Fifty-four NAFLD patients were consecutively enrolled. All patients underwent clinical and laboratory evaluation and liver biopsy. Patients were divided into two groups by the presence of NAFL or NASH. We measured vascular reactivity induced by patients' platelets on isolated mice aorta rings. Immunoblot assays for platelet-derived phosphorylated-eNOS (p-eNOS) and immunohistochemistry for hepatic p-eNOS have been performed to evaluate eNOS function in platelets and liver specimens. Flow-mediated-dilation (FMD) was also performed. Data were compared with healthy controls.Results: Twenty-one (38, 8%) patients had NAFL and 33 (61, 7%) NASH. No differences were found between groups and controls except for HOMA and insulin (p < 0.0001). Vascular reactivity demonstrated a reduced function induced from NAFLD platelets as compared with controls (p < 0.001), associated with an impaired p-eNOS in both platelets and liver (p < 0.001). NAFL showed a higher impairment of eNOS phosphorylation in comparison to NASH (p < 0.01). In contrast with what observed in vitro, the vascular response by FMD was worse in NASH as compared with NAFL.Conclusions: Our data showed, for the first time in humans, that NAFLD patients show a marked eNOS dysfunction, which may contribute to a higher CV risk. eNOS dysfunction observed in platelets and liver tissue didn't match with FMD.

Abrikossoffov tumor rijetka je dobroćudna neoplazma mekih tkiva i može se pojaviti na bilo kojem dijelu tijela, uključujući i orofacijalno područje. Obično je benigan, ali postoje podatci da je lokalno bio agresivan i maligan s udaljenim metastazama. Etiologija je nepoznata jer je u nekoliko istraživanja dokazano da zahvaća različite stanice. U prikazanom slučaju riječ je o Dominikanki u dobi od 36 godina koja je upućena na Odjel oralne i maksilofacijalne kirurgije poliklinike Federico Drugi u Napulju zbog ograničene i na opip čvoraste lezije od 17 milimetara na dorzumu jezika. Terapija se sastojala od ekscizijske biopsije na temelju dijagnostičke hipoteze o Abrikossoffovu tumoru, što je potvrđeno histopatološkom analizom te histokemijskom i imunokemijskom procjenom. Abrikossoffov tumor rijetka je neoplazma koja se mora oprezno dijagnosticirati nakon što se uzmu u obzir svi histološki i klinički parametri radi pravilnoga odabira terapije., Abrikossoff’s tumour is a rare benign soft tissue neoplasm that can occur in any part of the body, including the orofacial region. The tumour is usually benign, but there are reports of cases in which the tumour shows a locally aggressive behaviour, malignancy, and distant metastases. The aetiology is unknown, since several studies have shown that different cells are involved. In the present case, a 36-year-old Dominican woman was referred to the Department of Oral and Maxillofacial Surgery in Policlinico Federico II, Naples with a circumscribed lesion and sessile nodule on the dorsum of the tongue measuring about 17 mm in diameter. The treatment consisted of an excisional biopsy performed on the basis of the diagnostic hypothesis of Abrikossoff’s tumour, which was confirmed by histopathological analysis and histochemistry and immunohistochemistry evaluation. Abrikossoff’s tumour is an uncommon neoplasm which must be carefully diagnosed considering all the histological and clinical aspects in order to be treated correctly.

Community-acquired pneumonia (CAP) is complicated by cardiac events in the early phase of the disease. Aim of this study was to assess if these intrahospital cardiac complications may account for overall mortality and cardiovascular events occurring during a long-term follow-up. Three hundred one consecutive patients admitted to the University-Hospital, Policlinico Umberto I, with community-acquired pneumonia were prospectively recruited and followed up for a median of 17.4 months. Primary end point was the occurrence of death for any cause, and secondary end point was the occurrence of cardiovascular events (cardiovascular death, nonfatal myocardial infarction [MI], and stroke). During the intrahospital stay, 55 patients (18%) experienced a cardiac complication. Of these, 32 had an MI (29 non-ST-elevation MI and 3 ST-elevation MI) and 30 had a new episode of atrial fibrillation (7 nonmutually exclusive events). During the follow-up, 89 patients died (51% of patients with an intrahospital cardiac complication and 26% of patients without, p0.001) and 73 experienced a cardiovascular event (47% of patients with and 19% of patients without an intrahospital cardiac complication, p0.001). A Cox regression analysis showed that intrahospital cardiac complications, age, and Pneumonia Severity Index were significantly associated with overall mortality, whereas intrahospital cardiac complications, age, hypertension, and diabetes were significantly associated with cardiovascular events during the follow-up. In conclusion, this prospective study shows that intrahospital cardiac complications in the early phase of pneumonia are associated with an enhanced risk of death and cardiovascular events during long-term follow-up.