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Background: In spite of the increased use of Trans-catheter Aortic Valve Implantation (TAVI) due to the better patient selection, well-trained operators and improved technology, the choice of the best anesthesia regimen remains an open question. In particular, it remains to be clarified whether deep sedation (DS) in spontaneous breathing or femoral local anesthesia (LA) is best., Objective: This study compared the hemodynamic variations determined by deep sedation (DS) with spontaneous breathing and local femoral anesthesia (LA) in 2 groups of patients submitted to TAVI with two different kinds of anesthesia, using a beat-by-beat pulse contour method (MostCare ®-UP )., Methods: 82 patients with severe aortic stenosis and similar baseline characteristics and indications underwent trans-femoral TAVI: 50 with LA and 32 with DS. All patients were submitted to minimally invasive hemodynamic monitoring. The following parameters were measured: pressure indexes : systolic, diastolic, mean (SysP, DiaP, MAP) and dicrotic (DicP) pressures; flow indexes : cardiac output (CO), stroke volume (SV); ventriculo-arterial coupling indexes (VAC): peripheral arterial elastance (Ea P ), systemic vascular resistance (SVR); cardiovascular system performance : cardiac cycle efficiency (CCE), dP/dt max&#95;rad ., Results: The TAVI procedure was successful in 89% of patients (VARC-2 criteria) with no difference between the 2 groups. Anesthesia induction determined a higher decrease of pressures in DS than in LA (P<0.01) with no differences in CO. The VAC parameters (Ea P , SVR) decreased (P<0.01) in DS with an improvement in CCE (P<0.001); these parameters did not change in LA. The post-TAVI flow and VAC parameters, especially Ea, increased (P<0.05) more significantly in the LA group than in the DS group (P<0.001). Using logistic regression, the occurrence of the post-TAVI aortic regurgitation was correctly associated with the pressure gradient MAP-DicP in 63% of the study population (P=0.033). This association was more effectively detected in the LA group (78%, P=0.011) with a ROC AUC=0.779, than the DS group., Conclusion: The use of the pulse contour method to track the fast-hemodynamic changes during the TAVI procedure proved suitable for the aim. As expected, LA and DS induced different pre-TAVI hemodynamic conditions, which influenced the post-TAVI hemodynamic changes. The hemodynamic conditions induced by LA, enabled the occurrence of post-TAVI aortic regurgitation to be detected more effectively., Competing Interests: S.M. Romano is owner of the PRAM method patent. D. Payen received grant from Vygon Ltd (Ecouen, France) for clinical study and development on PRAM system. Other authors have no conflict of interests to declare., (AJCD Copyright © 2020.)

Background: Carotid endarterectomy is typically performed using either regional or general anesthesia techniques, which exhibit several differences, especially regarding the intraoperative neurological monitoring of patients. In this study, we introduce a technique of general anesthesia (cooperative patient general anesthesia), which allows neurological monitoring of the awake patient during surgery., Methods: We prospectively enrolled 181 consecutive adult patients scheduled for carotid endarterectomy. Patients were anesthetized with a total i.v. anesthesia technique. During carotid clamping, anesthesia was reduced and maintained only with high-dose remifentanil, such that the patient was able to respond to verbal statements and neurological monitoring could be performed. The technique is described in detail. Patient neurological and cardiac outcomes were investigated. Patient and surgeon satisfaction with the technique were also evaluated., Results: General anesthesia with a cooperative patient was achieved in 179 patients. No postoperative neurological events were observed. Two (1.1%) nonfatal myocardial infarctions occurred in the early postoperative period in two patients. Eighty-one percent of patients described the operation duration as brief, whereas 19.3% accurately perceived the time they were conscious. Both patients and surgeons were highly satisfied with the technique., Conclusions: In our series, cooperative patient general anesthesia proved to be a safe and satisfactory anesthetic technique for both the patient and surgeon. The technique was characterized by hemodynamic stability, excellent control of ventilatory pattern, continuous neurological monitoring, and immediate and safe conversion to general anesthesia whenever required. Further studies are needed to highlight the advantages of this technique compared with standard general and local anesthesia.

Objective: Oxidative stress has been suggested as a contributor of Alzheimer disease (AD) neurodegeneration, particularly in those patients with late-onset AD (LOAD). Therefore, the authors studied the effect of glutathione S-transferase (GST) P1-M1-T1 gene polymorphisms and their interactions with the apolipoprotein E (ApoE) epsilon4 allelic variant on the three-year longitudinal course of AD., Methods: Global cognitive level as measured by the Mini-Mental State Exam, basic activities of daily living (BADLs) as measured by the Physical Self-Maintenance Scale, and behavior as measured by the Neuropsychiatric Inventory, were assessed at baseline and after 1, 2, and 3 years in a sample of 99 LOAD patients. These subjects were drug naive and had undergone the first clinical examination for the diagnosis of AD., Results: A multiple regression analysis indicated that the presence of ApoE epsilon4 allelic variant or GSTT1 null phenotype predicted the faster age at onset of the illness (F = 5.76, df = 2, 96, p = 0.0043). Carriers of GSTP1 *C allelic variant had a faster decline in cognitive functions (repeated measures analysis of variance [ANOVA]: F = 4.00, df = 3, 285, p = 0.008) and in BADLs (repeated measures ANOVA: F = 5.27, df = 3, 285, p = 0.001). This faster decline was independent from ApoE epsilon4 allele possession. No effect of GST P1-M1-T1 polymorphisms was found on behavioral symptom severity., Conclusion: These data are in line with the hypotheses that oxidative damage is a prominent feature in the clinical progression and the age at onset of LOAD.

Background: Oxidative stress and neuronal cell death have been implicated in the pathogenesis of Alzheimer disease (AD). Considering that the glutathione transferase (GST) supergene family encodes isoenzymes that appear to be critical in protection against oxidative stress, we aimed at determining the various GSTP1, GSTM1, and GSTT1 polymorphisms and ApoE genotypes to investigate their role as susceptibility genes for late-onset AD (LOAD)., Methods: We included 210 LOAD patients and 228 healthy controls matched for age, sex, and educational level in our case-control genetic association study. GSTM1 and GSTT1 genotypes were studied by conventional PCR, whereas GSTP1 and ApoE genotypes were determined by real-time PCR on the LightCycler., Results: We found a significant association between LOAD and the GSTP1*C allelic variant [odds ratio (OR) = 1.9; P < 0.05], but no association between the GSTM1 and GSTT1 deleted genotypes and LOAD. In addition, a preliminary result suggested that carriers of both the GSTP1*C and ApoE epsilon4 allelic variants were at increased risk of LOAD (OR = 19.98; P < 0.0001)., Conclusion: The GSTP1*C allelic variant should be considered a candidate for LOAD, particularly in persons having the ApoE epsilon4 allelic variant, because the GSTP1 and ApoE gene products are implicated in oxidative stress and apoptosis processes leading to beta-amyloid-mediated neurodegeneration.

The present paper provides a synthetic account of the process of renewal and transformation of psychiatric care in Umbria, and, more specifically, in Perugia, in the last two decades. In the first part we attempt to show that the significance assigned to the normative aspect in the framework of psychiatric care in Italy has been excessive, particularly in the last few years. In the second, we try to give an account of the psychiatric work done in Umbria. We deal first with the period preceding the passing of Law no. 180 by the Italian Parliament; then we discuss the relationship between the new law and the processes in action; finally, we consider more recent problems concerning the attempts to promote a psychiatric counter-reformation and the theory and practice of our work.