Explore the vast range of titles available.

Background Risk stratification and management of acute myocardial infarction patients continue to be challenging despite considerable efforts made in the last decades by many clinicians and researchers. The aim of this study was to investigate the metabolomic fingerprint of acute myocardial infarction using nuclear magnetic resonance spectroscopy on patient serum samples and to evaluate the possible role of metabolomics in the prognostic stratification of acute myocardial infarction patients. Methods In total, 978 acute myocardial infarction patients were enrolled in this study; of these, 146 died and 832 survived during 2 years of follow-up after the acute myocardial infarction. Serum samples were analyzed via high-resolution 1 H-nuclear magnetic resonance spectroscopy and the spectra were used to characterize the metabolic fingerprint of patients. Multivariate statistics were used to create a prognostic model for the prediction of death within 2 years after the cardiovascular event. Results In the training set, metabolomics showed significant differential clustering of the two outcomes cohorts. A prognostic risk model predicted death with 76.9% sensitivity, 79.5% specificity, and 78.2% accuracy, and an area under the receiver operating characteristics curve of 0.859. These results were reproduced in the validation set, obtaining 72.6% sensitivity, 72.6% specificity, and 72.6% accuracy. Cox models were used to compare the known prognostic factors (for example, Global Registry of Acute Coronary Events score, age, sex, Killip class) with the metabolomic random forest risk score. In the univariate analysis, many prognostic factors were statistically associated with the outcomes; among them, the random forest score calculated from the nuclear magnetic resonance data showed a statistically relevant hazard ratio of 6.45 ( p = 2.16×10 −16 ). Moreover, in the multivariate regression only age, dyslipidemia, previous cerebrovascular disease, Killip class, and random forest score remained statistically significant, demonstrating their independence from the other variables. Conclusions For the first time, metabolomic profiling technologies were used to discriminate between patients with different outcomes after an acute myocardial infarction. These technologies seem to be a valid and accurate addition to standard stratification based on clinical and biohumoral parameters.

Background Ischemic stroke is a leading cause of disability and mortality, particularly among the elderly. Recanalization therapies, including thrombolysis and thrombectomy, are essential for restoring blood flow and saving ischemic tissue. However, these interventions may trigger reperfusion injury, worsening inflammation and tissue damage, leading to blood-brain-barrier (BBB) disruption, cerebral edema (CE) and adverse functional outcomes. Here we propose a model integrating circulating inflammatory biomarkers with metabolomic and lipoproteomic data able to help clinicians in predicting BBB disruption, CE at 24 h post stroke onset and poor post-stroke functional outcome (Modified Rankin Scale (mRS > 2). Methods Peripheral blood from 87 patients was collected at admission and 24 h after stroke onset. The logistic LASSO regression algorithm was employed to identify the optimal combination of metabolites, lipoprotein-related parameters and circulating biomarkers to discriminate the groups of interest at the two time-points. Results Multivariable logistic regression models included as covariates: age, sex, onset-to-treatment time, treatment with lipid-lowering medications before stroke, history of heart failure, history of atrial fibrillation and history of diabetes. The regression models showed that methionine, acetate, GlyA and MMP-2 were significant predictors of BBB disruption, methionine, acetate, TIMP-1 and CXCL-10 predicted 24-hours CE, whereas a poor functional outcome at three months was predicted by CXCL-10, IL-12 and LDL-5. Conclusions As stroke has a heterogeneous pathophysiology, a personalized approach based on biomarkers, as presented in this study, shown to be effective in tackling patient individual risk and could help in developing novel diagnostic, prognostic, and therapeutic neuroprotective strategies for the management of stroke patients.

Despite great advances with the introduction of ticagrelor and prasugrel in the treatment of acute coronary syndromes (ACS), the risk of thrombosis and bleeding remains significant and affects the choice of clinicians in the treatment of the single patient. Large registries are effective tools to explore patterns of drug administration and adherence to guideline recommendations in real-world clinical practice. START- antiplatelet is a prospective, observational registry carried out by seven Italian cardiology institutions on patients admitted for ACS aimed to document the real world treatment of ACS patients, adding also data on 12-month follow-up. We present data on the first 1050 patients who have completed 1-year follow-up on a total of 1537 patients. Primary end-points were: 1) MACCE (Major Adverse Cardiovascular and Cerebrovascular Events) including all-cause and cardiovascular mortality, non fatal MI, urgent revascularization, TIA and ischemic stroke; 2) Major and minor bleeding according to TIMI, GUSTO and ISTH classifications. The dual antiplatelet treatment most prescribed was aspirin plus ticagrelor (47.9%) and aspirin plus clopidogrel (32.1%). At a mean follow-up was 335±131 days, both ticagrelor and prasugrel are associated with a statistically significant reduced total and cardiovascular mortality. Both prasugrel and ticagrelor do not show a significant increased incidence of major and minor bleedings with respect to clopidogrel. Patients with monotherapy had significantly higher incidence of both ischemic stroke and major bleedings. The analysis of the register has documented that both ticagrelor and prasugrel are associated with a statistically significant reduced total and cardiovascular mortality but both do not show a significant increased incidence of major and minor bleedings with respect to clopidogrel.

Inclisiran is a subcutaneously administered synthetic small interfering RNA directed against proprotein convertase subtilisin-kexin type 9, leading to sustained low-density lipoprotein cholesterol (LDL-C) reduction with a twice-yearly dosing regimen. While its lipid-lowering efficacy is well established, its broader metabolic effects remain incompletely characterized. This study aimed to comprehensively evaluate serum metabolomic and lipoproteomic changes in patients with dyslipidemia before and after inclisiran treatment using an integrated nuclear magnetic resonance (NMR)-based approach. This observational single-center study included 69 patients with dyslipidemia treated with inclisiran in routine clinical practice. Fasting serum samples were collected at baseline and 3 months after treatment initiation. A total of 30 metabolites and 112 lipoprotein-related parameters were quantified using NMR spectroscopy. Paired comparisons between time points were performed using the Wilcoxon signed-rank test with false discovery rate correction. Clustering based on lipoprotein changes was conducted using the KODAMA algorithm to identify distinct response patterns. Inclisiran treatment was associated with extensive and coherent reductions in lipoprotein-related parameters. Seventy-four lipoprotein variables showed significant changes. Reductions were observed across LDL, IDL, and VLDL subclasses, while some HDL-related parameters were increased. In contrast, the global metabolomic profile remained largely unchanged; trimethylamine-N-oxide (TMAO) was the only metabolite significantly increased at follow-up. KODAMA clustering identified three patient groups with heterogeneous responses. Two groups demonstrated marked lipoprotein reductions, particularly those with higher baseline LDL-related parameters, whereas one group exhibited minimal changes. Baseline TMAO levels were lower in the group with the most pronounced lipid response and increased at follow-up, potentially reflecting changes in concomitant lipid-lowering therapy rather than a direct effect of inclisiran. Inclisiran induces a broad and consistent improvement in lipoprotein profiles, extending beyond LDL-C reduction, with minimal impact on the overall metabolome. These findings support the highly specific lipid-lowering action of inclisiran and highlight inter-individual variability in treatment response, especially in concomitant lipid-lowering therapies.

Background Apolipoproteins have been recently proposed as novel markers of cardiovascular disease (CVD) risk. However, evidence regarding effects of diet on apolipoproteins is limited. Aim To compare the effects of Mediterranean diet (MD) and lacto-ovo vegetarian diet (VD) on apolipoproteins and traditional CVD risk factors in participants with low-to-moderate CVD risk. Methods Fifty-two participants (39 women; 49.1 ± 12.4 years), followed MD and VD for 3 months each. Medical and dietary information was collected at the baseline. Anthropometric parameters and blood samples were obtained at the beginning and the end of interventions. Results MD and VD resulted in significant improvement in anthropometric and lipid profiles. Both diets led to a reduction in most of the inflammatory parameters. As for apolipoproteins, a significant change was observed for ApoC-I after VD (+ 24.4%; p  = 0.020). MD led to a negative correlation between ApoC-III and carbohydrates (R = − 0.29; p  = 0.039) whereas VD between ApoD and saturated fats (R = − 0.38; p  = 0.006). A positive correlation emerged after VD between HDL and ApoD (R = 0.33; p  = 0.017) and after MD between plasma triglycerides and ApoC-I (R = 0.32; p  = 0.020) and ApoD (R = 0.30; p  = 0.031). IL-17 resulted to be positively correlated with ApoB after MD (R = 0.31; p  = 0.028) and with ApoC-III after VD (R = 0.32; p  = 0.019). Subgroup analysis revealed positive effects on apolipoproteins from both diets, especially in women, individuals older than 50 years-old or with < 3 CVD risk factors. Conclusions Both diets seem to improve CVD risk, however, MD showed a greater positive effect on apolipoproteins in some subgroups, thus suggesting how diet may influence new potential markers of CVD risk. Trial registration : registered at clinicaltrials.gov (identifier: NCT02641834) on December 2015.

Aim of the present study was to evaluate whether monitoring direct oral anticoagulant (DOAC) levels may improve management of anticoagulated patients who need surgery for hip fracture. A total of 147 out of 2231 (7.7%) patients with hip fracture admitted to a tertiary teaching hospital were on DOACs (group A), whereas 206 patients matched for age, sex, and type of fracture not on anticoagulant or P2Y12 platelet inhibitors were considered as control group (group B). Patients on DOACs were divided into two subgroups: A1 in which intervention was scheduled in relation to the last drug intake according to current guidelines, and A2 included patients in whom time of surgery (TTS) was defined according to DOAC levels. Neuraxial anesthesia was considered with DOAC levels <30 ng/mL, general anesthesia for levels in the range 30-50 ng/mL. TTS was significantly lower in controls than in DOAC patients: surgery within 48 hours was performed in 80.6% of group B versus 51% in group A ( <0.0001). In A2, 41 patients underwent surgery within 48 hours (56%) in comparison to 32 A1 patients (45.1%; =0.03). TTS and length of hospitalization were on average 1 day lower in patients with assay of DOAC levels. Finally, 35/39 (89%) patients with DOAC levels <50 ng/mL had surgery within 48 hours (26 under neuraxial anesthesia, without any neurological complication, and 13 in general anesthesia). DOAC assay in patients with hip fracture may be useful for correct definition of time to surgery, particularly in patients who are candidates for neuraxial anesthesia. Two-thirds of patients with DOAC levels <50 ng/mL at 48 hours from last drug intake underwent uneventful neuraxial anesthesia, saving at least 24 hours in comparison to guidelines.

The aim of the present study was to examine the effect of a replacement diet with organic, semi-whole-grain products derived from Triticum turgidum subsp. turanicum (ancient) wheat on irritable bowel syndrome (IBS) symptoms and inflammatory/biochemical parameters. A double-blinded randomised cross-over trial was performed using twenty participants (thirteen females and seven males, aged 18–59 years) classified as having moderate IBS. Participants received products (bread, pasta, biscuits and crackers) made either from ancient or modern wheat for 6 weeks in a random order. Symptoms due to IBS were evaluated using two questionnaires, which were compiled both at baseline and on a weekly basis during the intervention period. Blood analyses were carried out at the beginning and end of each respective intervention period. During the intervention period with ancient wheat products, patients experienced a significant decrease in the severity of IBS symptoms, such as abdominal pain (P< 0·0001), bloating (P= 0·004), satisfaction with stool consistency (P< 0·001) and tiredness (P< 0·0001). No significant difference was observed after the intervention period with modern wheat products. Similarly, patients reported significant amelioration in the severity of gastrointestinal symptoms only after the ancient wheat intervention period, as measured by the intensity of pain (P= 0·001), the frequency of pain (P< 0·0001), bloating (P< 0·0001), abdominal distension (P< 0·001) and the quality of life (P< 0·0001). Interestingly, the inflammatory profile showed a significant reduction in the circulating levels of pro-inflammatory cytokines, including IL-6, IL-17, interferon-γ, monocyte chemotactic protein-1 and vascular endothelial growth factor after the intervention period with ancient wheat products, but not after the control period. In conclusion, significant improvements in both IBS symptoms and the inflammatory profile were reported after the ingestion of ancient wheat products.

Background Life expectancy has increased over the last century and a growing number of people is reaching age 90 years and over. However, data on nonagenarians’ health trends are scarce due to difficulties in investigating this specific population. This study aims to identify risk factors for one-year mortality in nonagenarians using data collected within the “Mugello Study”. Methods Complete information on sociodemographic data, cognitive and functional status, lifestyle, medical history, and drug use was collected from 433 nonagenarians, as well as information about survival after 1 year from the interview. Results The sample included 314 women (72.5%) and 119 men (27.5%) with a median age of 92 years (range 90-99 years). The mortality rate was 20.3% (88 deaths). After adjustment for age and sex, a significantly higher risk of dying within 12 months was observed in individuals with more severe cognitive impairment (HR = 5.011, p  < 0.001), more severe disability in basic activities of daily living (HR = 4.193, p  < 0.001), sedentary lifestyle (HR = 3.367, p  < 0.001), higher number of drugs assumed (HR = 1.118, p  = 0.031), and kidney dysfunction (HR = 2.609, p  = 0.004). When all the variables were included in the analysis, only older age (HR = 1.079, p  = 0.048), lower cognitive function (HR = 2.859, p  = 0.015), sedentary lifestyle (HR = 2.030, p  = 0.026), and kidney dysfunction (HR = 2.322, p  = 0.018) remained significantly associated with reduced survival. Conclusions Data from the Mugello study support the hypothesis that survival at 12 months in nonagenarians is not a stochastic process and that older age, reduced cognitive function, sedentary lifestyle, and the presence of kidney dysfunction are associated with mortality.

Ischemic stroke caused by the abrupt interruption of blood flow is one of the leading causes of death and disability worldwide. Despite expanding reperfusion treatment indications, a significant proportion of patients (54.5%) experiences poor outcomes, regardless of successful recanalization, emphasizing the need for clinically relevant preclinical stroke models to better understand the mechanisms associated with effective reperfusion. Here, we develop and characterize a novel mouse model of light-induced recanalization following the photothrombotic occlusion of the distal branch of the middle cerebral artery (MCA). The recanalization provides a meaningful reduction of the infarct volume compared to non-recanalized mice. Moreover, the generalized motor impairment is less severe, as measured by the Neuro Deficit score. Ex vivo investigation highlights that light-mediated recanalization mitigates astrocyte complexity in the periinfarct cortex of recanalized mice. Moreover, light-induced recanalization reduces cerebral edema occurrence. Finally, the investigation of circulating biomarkers shows that our model of occlusion and recanalization of the MCA recapitulates the neuroinflammatory cascade of the acute phase of ischemic stroke. The all-optical occlusion/recanalization mouse model of stroke developed represents a valuable translational tool to study acute ischemic stroke and its neuroinflammatory response.

Background Deep vein thrombosis (DVT) is a frequent complication in elderly patients undergoing surgery for proximal femoral fractures. Identifying early coagulation and viscoelastic changes may help to personalize thromboprophylaxis strategies. This study evaluated the temporal evolution of coagulation and ROTEM parameters and explored whether baseline values and early changes could predict the development of asymptomatic DVT. Methods We conducted a prospective observational study including patients ≥ 80 years undergoing surgical repair of proximal femoral fractures. Conventional coagulation tests and ROTEM were performed at admission (T0) and on postoperative day 3 (T3). Compression ultrasonography was used to screen for DVT on day 5 (T5). Longitudinal changes were assessed with linear mixed-effects models. Results Among 40 enrolled patients, 7 (17.5%) developed asymptomatic DVT. Platelet count was consistently higher in DVT patients (baseline: 275.0 ± 47.1 vs 186.5 ± 54.9 × 10 9 /L; p  < 0.001). ROTEM revealed increased EXTEM maximum clot firmness (67.6 ± 1.7 vs 62.2 ± 5.7 mm; p  = 0.024) and shorter clot formation time (92.0 ± 9.3 vs 116.1 ± 32.0 s; p  = 0.041). Fibrinogen levels diverged over time: while baseline values were comparable, DVT patients showed progressive increases (+ 43.7 mg/dL/day) versus reductions in non-DVT patients (-9.5 mg/dL/day), yielding significant differences at T3 (525.3 ± 177.0 vs 372.1 ± 177.8 mg/dL; p  = 0.015). FIBTEM-MCF did not differ between groups. A baseline platelet count ≥ 277 × 10 9 /L predicted DVT with 71% sensitivity and 97% specificity (AUC 0.896). Conclusion In elderly patients with femoral fractures, asymptomatic DVT was associated with elevated baseline platelet counts, enhanced clot firmness, and progressive fibrinogen elevation over time. These findings suggest multifaceted hypercoagulable abnormalities with temporal monitoring potentially superior to single-timepoint assessments for DVT prediction.