Abstract The DIDO is the time between the patient‘s arrival in a center without haemodynamics and the departure by ambulance towards the center with haemodynamics. It affects the D2B and the patient‘s prognosis and is an indicator of the effectiveness of the performance on STEMI care when it is less than 30 minutes. From 2009, a protocol was developed on the management of PCI in our hospital, whose primary objective was the containment of DIDO within 30 minutes. After the application of this protocol we went to evaluate our performance on patients who arrived consecutively from 1 January 2022 to 31 December 2022 at the San Benedetto del Tronto ED, Spoke centre not equipped with haemodynamics. Inclusion criteria: age over 18 years, chest pain <12 hours, discharge diagnosis of STEMI ACS. Excluded 2 patients with cardiac arrest admitted to the ICU, 2 patients with diagnostic uncertainty centralized subsequently, 2 patients with no indication for PCI in emergency admitted to the Cardiac Intensive Care Unit, there are 35 patients, 10 females (29%) and 25 males (71%), with an average age of 64.57 years. Comorbidities were present in 71% of patients (cardiovascular pathologies, diabetes and obesity), while in 29% of patients no comorbidity was present. No comorbidity was observed in 60% of patients between 18 and 55 years and in 30% of patients between 65 and 75 years. We evaluate our performance by comparing the trend, over the years, of this indicator. A reduction in the average DIDO was achieved from 56 minutes in 2014 to 33 minutes in 2022 reaching the value of 17 minutes in 75% of cases. The percentage of cases outside the cut off is 25.71%. We tried to hypothesize the causes responsible for a DIDO>30 minutes: an inappropriate attribution of the priority color code to Triage, the presence of comorbidities. In reality, as well as data from international literature, cases of DIDO >30 minutes were associated with delay accumulated for necessary specialist consultations for difficult to interpret ECGs and the delay of the transport the patient to the Hub hospital. To conclude is necessary direct centralization of STEMI ACS patients from 118 to haemodynamics and reduce centralization decision–making times by identifying criteria facilitating the transfer decision in cases of difficult–to–interpret ECGs.
It has been well documented that β-amyloid peptide accumulation and aggregation in the brain plays a crucial role in the pathophysiology of Alzheimer's disease (AD). However, a new orientation of the amyloid cascade hypothesis has evidenced that soluble forms of the peptide (sAβ) are involved in Aβ-induced cognitive impairment and cause rapid disruption of the synaptic mechanisms underlying memory. The primary aim of this study was to elucidate the effects of sAβ, acutely injected intracerebrally (i.c.v., 4 µM), on the short term and long term memory of young adult male rats, by using the novel object recognition task. Glutamatergic receptors have been proposed as mediating the effect of Aβ on synaptic plasticity and memory. Thus, we also investigated the effects of sAβ on prefrontal cortex (PFC) glutamate release and the specific contribution of N-methyl-D-aspartate (NMDA) receptor modulation to the effects of sAβ administration on the cognitive parameters evaluated. We found that a single i.c.v. injection of sAβ 2h before testing did not alter the ability of rats to differentiate between a familiar and a novel object, in a short term memory test, while it was able to negatively affect consolidation/retrieval of long term memory. Moreover, a significant increase of glutamate levels was found in PFC of rats treated with the peptide 2 h earlier. Interestingly, memory deficit induced by sAβ was reversed by a NMDA-receptor antagonist, memantine (5 mg/kg i.p), administered immediately after the familiarization trial (T1). On the contrary, memantine administered 30 min before T1 trial, was not able to rescue long term memory impairment. Taken together, our results suggest that an acute i.c.v. injection of sAβ peptide interferes with the consolidation/retrieval of long term memory. Moreover, such sAβ-induced effect indicates the involvement of glutamatergic system, proposing that NMDA receptor inhibition might prevent or lead to the recovery of early cognitive impairment.
Nitric oxide (NO) is one of the most important mediators and neurotransmitters and its levels change under pathological conditions. NO production may be regulated by endogenous nitric oxide synthase (NOS) inhibitors, in particular asymmetric dimethylarginine (ADMA). Most of the interest is focused on ADMA, since this compound is present in plasma and urine and accumulation of ADMA has been described in many disease states but little is known about cerebrospinal fluid (CSF) concentrations of this compound and of its structural isomer symmetric dimethylarginine (SDMA). To determine the levels of methylarginines, we here present a new hydrophilic interaction chromatography (HILIC)-MS/MS method for the precise determination of these substances in CSF from microdialysis samples of rat prefrontal cortex (PFC). The method requires only minimal sample preparation and features isotope-labelled internal standards.
In this study we evaluated the role of three currently available therapeutic regimens in the treatment of early stages of idiopathic pulmonary fibrosis (IPF).The study population consisted of 57 consecutive suspected individuals with IPF. Patients with interstitial pneumonias other than IPF and subjects with advanced disease or contraindication to therapy were excluded. We evaluated 30 subjects with mild-moderate IPF, homogeneous baseline characteristics and prognostic parameters that were assigned to 3 treatment regimens: group 1 (n = 11): prednisone 1 mg/kg/ day; group 2 (n = 9): prednisone 0.5 mg/kg/day plus cyclophosphamide 100 mg/day; group 3 (n = 10): prednisone 0.5 mg/kg/day plus colchicine 1 mg/day. We analysed response to therapy by analysis of a clinical-radiographic-physiologic (CRP) score before treatment and at 6 months intervals for 18 months. Side effects and three years survival rate were also investigated.Although our study was performed in a subset of patients with early disease's stages, these data showed that none of the regimens was able to interfere with IPF's course. However treatment with colchicine plus prednisone resulted in fewer side effects and re-evaluation parameters showed a significant decrease of dyspnoea (p < 0.01). No significant differences were observed in survival rate among the three groups.None of the regimens analyzed was effective even in the treatment of the early stages of IPF. The association colchicine/corticosteroids could be considered a safe and not expensive regimen that may be used in the treatment of IPF, especially in patients who have experienced adverse effects from immunosuppressive agents, while waiting for newer therapeutic strategies.
Aims: Psychosocial stress alters the hypothalamic-pituitary-adrenal axis (HPA-axis). Increasing evidence shows a link between these alterations and oxidant elevation. Oxidative stress is implicated in the stress response and in the pathogenesis of neurologic and psychiatric diseases. NADPH oxidases (NOXs) are a major source of reactive oxygen species (ROS) in the central nervous system. Here, we investigated the contributory role of NOX2-derived ROS to the development of neuroendocrine alterations in a rat model of chronic psychosocial stress, the social isolation. Results: Significant elevations in the hypothalamic levels of corticotropin-releasing factor and plasmatic adrenocorticotropic hormone were observed from 4 weeks of social isolation. Increased levels of peripheral markers of the HPA-axis (plasmatic and salivary corticosterone) were observed at a later time point of social isolation (7 weeks). Alteration in the exploratory activity of isolated rats followed the same time course. Increased expression of markers of oxidative stress (8-hydroxy-2-deoxyguanosine [8OhdG] and nitrotyrosine) and NOX2 mRNA was early detectable in the hypothalamus of isolated rats (after 2 weeks), but later (after 7 weeks) in the adrenal gland. A 3-week treatment with the antioxidant/NOX inhibitor apocynin stopped the progression of isolation-induced alterations of the HPA-axis. Rats with a loss-of-function mutation in the NOX2 subunit p47phox were totally protected from the alterations of the neuroendocrine profile, behavior, and increased NOX2 mRNA expression induced by social isolation. Innovation: We demonstrate that psychosocial stress induces early elevation of NOX2-derived oxidative stress in the hypothalamus and consequent alterations of the HPA-axis, leading ultimately to an altered behavior. Conclusion: Pharmacological targeting of NOX2 might be of crucial importance for the treatment of psychosocial stress-induced psychosis. Antioxid. Redox Signal. 18, 1385–1399.
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