Cardiac Output Evaluation on Septic Shock Patients: Comparison between Calibrated and Uncalibrated Devices during Vasopressor Therapy

There are no reliable, non-invasive methods to accurately measure cardiac output (CO) in septic patients. MostCare (Vytech Health (TM), Vygon, Padova, Italy), is a beat-to-beat, self calibrated method for CO measurement based on continuous analysis of reflected arterial pressure waveforms. We enrolled 40 patients that were suffering from septic shock and requiring norepinephrine infusion to target blood pressure in order to to evaluate the level of agreement between a calibrated transpulmonary thermodilution device (PiCCO System, Pulsion Medical Systems, Feldkirchen, Germany) and the MostCare system in detecting and tracking changes in CO measurements related to norepinephrine reduction in septic shock patients,. PiCCO was connected to a 5 Fr femoral artery catheter and to a central venous catheter. System calibration was performed with 15 mL of cold saline injection over about 3 s. The MostCare device was connected to the artery catheter to analyze the arterial waveform. Before reducing norepinephrine infusion, the PiCCO system was calibrated, the MostCare waveform was optimized, and the values of the complete hemodynamic profile were recorded (T1). Norepinephrine infusion was then reduced by 0.03 mcg/Kg/min. After 30 min, a new calibration of PiCCO system and a new record on both monitors were performed (T2). Static measurements agreements were assessed using the Bland-Altman test, while trending ability was investigated using polar plot analysis. If volume expansion occurred, then related data were separately analyzed. At T1 mean the CO was 5.38 (SD 0.60) L/min, the mean difference was 0.176 L/min, the limits of agreement (LoA) was +1.39 and -1.04 L/min, and the percentage error (PE) was 22.6%; at T2 the mean CO was 5.44 (SD 0.73) L/min, the mean difference was 0.053 L/min, the LoA was +1.51 and -1.40, and the PE was 27%. After considering the volume expansion between T1 and T2, the mean CO at T1 was 5.39 L/min (SD 0.47), the LoA was +1.09 and -0.78 L/min, and the percentage error (PE) was 17%; at T2 the mean CO was 5.35 L/min (SD 0.81), the LoA was +1.73 and -1.52 L/min, and the PE was 30%. The polar plot diagram seems to confirm the trending ability of MostCare system versus the reference method. In septic patients, when the arterial waveform is accurate, MostCare and PiCCO transpulmonary thermodilution exhibit good agreement even after the reduction of norepinephrine and changes in vascular tone or volume expansion. MostCare could be a rapid to set, reliable, and useful tool to monitor hemodynamic variations in septic patients in emergency contexts where thermodilution methods or other advanced systems are not easily available

Chlorination and tautomerism: a computational and UPS/XPS study of 2-hydroxypyridine ⇌ 2-pyridone equilibrium

The prototropic tautomeric equilibrium in 2-hydroxypyridine serves as a prototype model for the study of nucleobases' behaviour. The position of such an equilibrium in parent and chlorine monosubstituted 2-hydroxypyridine compounds in the gas phase was determined using synchrotron based techniques. The lactim tautomer is dominant for the 5- and 6-substituted compounds, whereas the parent, 3- and 4-substituted isomers have comparable populations for both tautomers. Information was obtained by measuring valence band and core level photoemission spectra at the chlorine L-edge and carbon, nitrogen, and oxygen K-edges. The effect of chlorine on the core ionization potentials of the atoms in the heterocycle was evaluated and reasonable agreement with a simple model was obtained. Basic considerations of resonance structures correctly predicts the tautomeric equilibrium for the 5- and 6-substituted compounds. The vibrationally resolved structure of the low energy portion of the valence band photoionization spectra is assigned based on quantum-chemical calculations of the neutral and charged species followed by simulation of the vibronic structure. It is shown that the first ionization occurs from a π orbital of similar shape for both tautomers. In addition, the highly distinctive vibronic structure observed just above the first ionization of the lactim, for three of the five species investigated, is assigned to the second ionization of the lactam.We gratefully acknowledge the financial support of University of Bologna (RFO), MIUR (FABR) and Fondazione Cassa di Risparmio di Bologna.HS acknowledges the TRIL fellowship awarded by the Abdus Salam International Centre for Theoretical Physics (ICTP), Trieste, Italy.Peer reviewe

Cognitive and Cortical Plasticity Deficits Correlate with Altered Amyloid-β CSF Levels in Multiple Sclerosis

Cognitive dysfunction is of frequent observation in multiple sclerosis (MS). It is associated with gray matter pathology, brain atrophy, and altered connectivity, and recent evidence showed that acute inflammation can exacerbate mental deficits independently of the primary functional system involved. In this study, we measured cerebrospinal fluid (CSF) levels of amyloid-β1−42 and τ protein in MS and in clinically isolated syndrome patients, as both proteins have been associated with cognitive decline in Alzheimer's disease (AD). In AD, amyloid-β1–42 accumulates in the brain as insoluble extracellular plaques, possibly explaining why soluble amyloid-β1–42 is reduced in the CSF of these patients. In our sample of MS patients, amyloid-β1–42 levels were significantly lower in patients cognitively impaired (CI) and were inversely correlated with the number of Gadolinium-enhancing (Gd+) lesions at the magnetic resonance imaging (MRI). Positive correlations between amyloid-β1–42 levels and measures of attention and concentration were also found. Furthermore, abnormal neuroplasticity of the cerebral cortex, explored with θ burst stimulation (TBS), was observed in CI patients, and a positive correlation was found between amyloid-β1–42 CSF contents and the magnitude of long-term potentiation-like effects induced by TBS. No correlation was conversely found between τ protein concentrations and MRI findings, cognitive parameters, and TBS effects in these patients. Together, our results indicate that in MS, central inflammation is able to alter amyloid-β metabolism by reducing its concentration in the CSF and leading to impairment of synaptic plasticity and cognitive function

Clinical Perception and Treatment Options for Behavioral and Psychological Symptoms of Dementia (BPSD) in Italy

Background: Behavioral and psychological symptoms of dementia (BPSD) have a high prevalence, and their presence is associated with a severe impact in terms of social costs. However, dedicated clinical tools or biomarkers to detect these symptoms are lacking. Thus, BPSD management in clinical settings is challenging. The aim of this study was to investigate the perception and the treatment strategies for BPSD in Italian centers working in the dementia field. Methods: A multicenter, national survey was developed by BPSD Study Group of the Italian Neurological Society for Dementia (SINDEM). The survey consisted of a semi-structured questionnaire that was e-mailed to SINDEM members, dementia centers part of the national network of memory clinics (Centers for Cognitive Deterioration and Dementia [CDCD]), and clinicians working in dementia care settings. The questions were focused on (1) perceived global frequency and relevance of BPSD; (2) tools used to assess BPSD; (3) pharmacological treatment for psychosis, apathy, agitation, aggression, depression, anxiety, sleep, and nutrition disturbances; (4) non-pharmacological treatments; (5) drugs side effects. Results: One-hundred and thirty-six clinicians participated in this study. Seventy-nine participants worked in a CDCD and 57 in other settings. The perceived frequency of BPSD was 74%. BPSD are detected by means of a clinical assessment for 96.3% or a caregiver interview for 97%. For psychosis treatment the first choice was atypical antipsychotics (83.3%), followed by typical antipsychotic (8.9%) and antidepressants (4.8%). For agitation, atypical antipsychotics were the first-choice treatment in 64% of cases and antidepressants in 16.1%. For aggression, the most used drugs were atypical antipsychotics (82.9%). For anxiety, 55.2% use antidepressants, 17.9% use atypical antipsychotics, and 16.9% use benzodiazepines. Interestingly, most of the centers apply non-pharmacological treatments for BPSD. Some differences emerged comparing the responses from CDCD and other care settings. Conclusion: The survey results revealed many differences in BPSD perception, treatment options, and observed side effect according to the clinical setting. This variability can be explained by the absence of clear guidelines, by differences in patients' characteristics, and by clinical practice based on subjective experience. These results suggest that producing guidelines for the pharmacological treatment of BPSD is a major need