Advanced age, time to treatment and long-term mortality: single centre data from the FAST-STEMI network

Background. Optimization of the techniques and larger accessibility to mechanical reperfusion have significantly improved the outcomes of patients with ST-segment elevation myocardial infarction (STEMI). However, suboptimal results have been observed in certain higher-risk subsets of patients, as in advanced age, where the benefits of primary PCI are more debated. We evaluated the impact of systematic primary percutaneous coronary intervention (PCI) and an optimized STEMI network on the long-term prognosis from a single centre experience.Methods. We included STEMI patients included in the FAST-STEMI network between 2016 and 2019. Ischemia duration was defined as the time from symptoms onset to coronary reopening (pain-to-balloon, PTB). The primary study endpoint (PE) was a composite of mortality and recurrent MI at long-term follow-up. Indywidual outcome endpoints were also assessed.Results. We included 253 patients undergoing primary PCI and discharged alive. Mean age was 67.2 ± 12.5 years, 75.1% males and 19.8% diabetics. At a median follow-up of 581 [307–922] days, the primary endpoint occurred in 24 patients (7.9%), of whom 5.5% died. The occurrence of a cardiovascular event was significantly associated with advanced age (p < 0.001), renal failure (p = 0.03), lower ejection fraction at discharge (p = 0.04) and longer in-hospital stay (p = 0.01). The median PTB was 198 minutes [IQR: 125–340 min], that was significantly longer among patients experiencing the PE (p = 0.01). A linear relationship was observed between age and PTB (r = 0.13, p = 0.009). However, both age ≥ 75 years and PTB above the median emerged as independent predictors of the primary endpoint (age: HR [95%CI] = 5.56 [2.26–13.7], p < 0.001, PTB: HR [95%CI] = 3.59 [1.39–9.3], p = 0.01). Similar results were observed for overall mortality.Conclusion. The present study shows that among STEMI patients undergoing primary PCI in a single centre, the duration of ischemia and advance age are independently associated to long-term mortality and recurrent myocardial infarction. However, longer time to reperfusion was observed among elderly patients

HGF and MET: From Brain Development to Neurological Disorders

Hepatocyte growth factor (HGF) and its tyrosine kinase receptor, encoded by the MET cellular proto-oncogene, are expressed in the nervous system from pre-natal development to adult life, where they are involved in neuronal growth and survival. In this review, we highlight, beyond the neurotrophic action, novel roles of HGF-MET in synaptogenesis during post-natal brain development and the connection between deregulation of MET expression and developmental disorders such as autism spectrum disorder (ASD). On the pharmacology side, HGF-induced MET activation exerts beneficial neuroprotective effects also in adulthood, specifically in neurodegenerative disease, and in preclinical models of cerebral ischemia, spinal cord injuries, and neurological pathologies, such as Alzheimer’s disease (AD), amyotrophic lateral sclerosis (ALS), and multiple sclerosis (MS). HGF is a key factor preventing neuronal death and promoting survival through pro-angiogenic, anti-inflammatory, and immune-modulatory mechanisms. Recent evidence suggests that HGF acts on neural stem cells to enhance neuroregeneration. The possible therapeutic application of HGF and HGF mimetics for the treatment of neurological disorders is discussed

Association of kidney disease measures with risk of renal function worsening in patients with type 1 diabetes

Background: Albuminuria has been classically considered a marker of kidney damage progression in diabetic patients and it is routinely assessed to monitor kidney function. However, the role of a mild GFR reduction on the development of stage 653 CKD has been less explored in type 1 diabetes mellitus (T1DM) patients. Aim of the present study was to evaluate the prognostic role of kidney disease measures, namely albuminuria and reduced GFR, on the development of stage 653 CKD in a large cohort of patients affected by T1DM. Methods: A total of 4284 patients affected by T1DM followed-up at 76 diabetes centers participating to the Italian Association of Clinical Diabetologists (Associazione Medici Diabetologi, AMD) initiative constitutes the study population. Urinary albumin excretion (ACR) and estimated GFR (eGFR) were retrieved and analyzed. The incidence of stage 653 CKD (eGFR < 60 mL/min/1.73 m2) or eGFR reduction > 30% from baseline was evaluated. Results: The mean estimated GFR was 98 \ub1 17 mL/min/1.73m2 and the proportion of patients with albuminuria was 15.3% (n = 654) at baseline. About 8% (n = 337) of patients developed one of the two renal endpoints during the 4-year follow-up period. Age, albuminuria (micro or macro) and baseline eGFR < 90 ml/min/m2 were independent risk factors for stage 653 CKD and renal function worsening. When compared to patients with eGFR > 90 ml/min/1.73m2 and normoalbuminuria, those with albuminuria at baseline had a 1.69 greater risk of reaching stage 3 CKD, while patients with mild eGFR reduction (i.e. eGFR between 90 and 60 mL/min/1.73 m2) show a 3.81 greater risk that rose to 8.24 for those patients with albuminuria and mild eGFR reduction at baseline. Conclusions: Albuminuria and eGFR reduction represent independent risk factors for incident stage 653 CKD in T1DM patients. The simultaneous occurrence of reduced eGFR and albuminuria have a synergistic effect on renal function worsening