Major trauma critical pathway: preliminary results from the monitoring system in the regional network and in a hub center in Rome metropolitan area.

OBJECTIVE: The aim of this study is to collect the two years' data regarding the Integrated Trauma Management System (SIAT) by capturing the activity of its three Hubs in the Italian Lazio Region and test the performance of one of the Hubs' (Fondazione Policlinico Universitario A. Gemelli - IRCCS, FPG -IRCCS) Major Trauma Clinical Pathway's (MTCP) monitoring system, introducing the preliminary results through volume, process and outcome indicators. MATERIALS AND METHODS: A retrospective analysis on SIAT was conducted on years 2016 to 2018, by collecting outcome and timeliness indicators through the Lazio Informative System whereas the MTCP was monitored through set of indicators from the FPG - IRCCS Informative System belonging to randomly selected clinical records of the established period. RESULTS: Hubs managed 11.3% of the 998,240 patients admitted in SIAT. All patients eligible for MTCP were "Flagged", and 83% underwent a CT within 2 hours; intra-hospital mortality was 13% whereas readmission rates 16.9%. CONCLUSIONS: SIAT converges the most severe patients to its Hubs. The MTCP monitoring system was able to measure a total of 9 out of 13 indicators from the original panel. This research may serve as a departing point to conduct a pre-post analysis on the performance of the MTCP.

IL-1-dependent electrophysiological changes and cardiac neural remodeling in a mouse model of Kawasaki disease vasculitis.

Kawasaki disease (KD) is the leading cause of acquired heart disease in children. In addition to coronary artery abnormalities, aneurysms and myocarditis, acute KD is also associated with echocardiogram (ECG) abnormalities in 40-80% of patients. Here, we show that these ECG changes are recapitulated in the Lactobacillus casei cell wall extract (LCWE)-induced KD vasculitis mouse model. LCWE-injected mice developed elevated heart rate and decreased R wave amplitude, with significant differences in prolonged ventricular repolarization. LCWE-injected mice developed cardiac ganglion inflammation, that may affect the impulse-conducting system in the myocardium. Furthermore, serum nerve growth factor (NGF) was significantly elevated in LCWE-injected mice, similar to children with KD vasculitis, associated with increased neural remodeling of the myocardium. ECG abnormalities were prevented by blocking interleukin (IL)-1 signaling with anakinra, and the increase in serum NGF and cardiac neural remodeling were similarly blocked in Il1r1-/- mice and in wild-type mice treated with anakinra. Thus, similar to clinical KD, the LCWE-induced KD vasculitis mouse model also exhibits electrophysiological abnormalities and cardiac neuronal remodeling, and these changes can be prevented by blocking IL-1 signaling. These data support the acceleration of anti-IL-1 therapy trials to benefit KD patients.

Enhanced expression of Organic Cation Transporters in bronchial epithelial cell layers following insults associated with asthma - Impact on salbutamol transport.

Increasing evidence suggests Organic Cation Transporters (OCT) might facilitate the absorption of inhaled bronchodilators, including salbutamol, across the lung epithelium. This is essentially scarred and inflamed in asthma. Accordingly, the impact of epithelial insults relevant to asthma on OCT expression and salbutamol transport was evaluated in air-liquid interfaced layers of the human broncho-epithelial cell line Calu-3. These were physically injured and allowed to recover for 48h or exposed to the pro-inflammatory stimulant lipopolysaccharide (LPS) for 48h and the aeroallergen house dust mite (HDM) for 8h twice over 48h. Increases in transporter expression were measured following each treatment, with the protein levels of the OCTN2 subtype consistently raised by at least 50%. Interestingly, OCT upregulation upon LPS and HDM challenges were dependent on an inflammatory event occurring in the cell layers. Salbutamol permeability was higher in LPS exposed layers than in their untreated counterparts and in both cases, was sensitive to the OCT inhibitor tetraethylammonium. This study is the first to show epithelial injury, inflammation and allergen abuse upregulate OCT in bronchial epithelial cells, which might have an impact on the absorption of their substrates in diseased lungs.

Non-cell-autonomous effects of vector-expressed regulatory RNAs in mammalian heart cells.

In mammalian cells, small regulatory RNA molecules are able to modulate gene expression in a cell-autonomous manner. In contrast, this mechanism of gene regulation can occur systemically in plants and nematodes. The existence of similar cell-to-cell transmission in mammalian cells has been explored, but generalizibilty and mechanistic insights have remained elusive. Here, we show that small regulatory RNA molecules are capable of a non-cell-autonomous effect between primary cardiac myocytes through a gap-junction-dependent mechanism. Co-culture experiments showed that both Dicer-processed small-interfering RNAs (siRNAs) and Drosha-processed microRNAs (miRNAs) were capable of target gene knockdown and physiological effects in a non-cell-autonomous manner. Target gene siRNA molecules were detected in recipient cells, indicating transfer of the primary effector molecule. All of these effects were abrogated by dominant-negative molecular suppression of gap junction function. Our results show that both siRNAs and miRNAs are capable of a non-cell-autonomous effect between mammalian cells through gap junctions. The recognition of this biological process raises the novel therapeutic prospect of a bystander effect after gene transfer to tissues bearing gap junctions and for cell engineering with a view to creating regulatory RNA donor cells that exert their influence throughout a syncytium.

Post-traumatic stress disorder-related symptoms after intensive care.

AIM: To determine the incidence of Post Traumatic Stress Disorder (PTSD) related symptoms in a population of intensive care unit (ICU) admitted patients and the relationship between PTSD-related symptoms and memories of ICU. METHODS: Adults consecutively admitted to an ICU of a University hospital during 1 year, who stayed in the ICU at least 3 days, were prospectively studied. A questionnaire (ICU memory tool) was administered to 84 patients 1 week after ICU discharge and to 63 of them after 3 months. Past medical history and clinical variables present during ICU stay were collected. RESULTS: At the 1st interview, 5 patients (5.9%) did not remember to have been in ICU. Of the remaining 79 patients (males 59.5%, median age 69 years, SAPS II 34, APACHE II 14 and ICU stay 5 days), 4 reported intrusive memories and none panic attacks. The Impact of Events Scale (IES), available in 3 of them, scored in medium/high levels. Only the median number of factual memories reported by the patients with and without intrusive memories was significantly different (4 interquartile range 2-5 vs 8 interquartile range 6-10; p=0.002). The patients with intrusive memories at the 1st interview did not report them at the 2nd interview. Two patients not having panic or intrusive memories at the 1st interview reported PTSD-related symptoms after 3 months. CONCLUSIONS: In a general ICU population, few patients (5%) have PTSD-related symptoms and those who present those symptoms report less factual memories of ICU stay.

Analgesia, sedation, and memory of intensive care.

PURPOSE: The purpose of this article was to investigate the relationship between analgesia, sedation, and memory of intensive care. PATIENTS AND METHODS: One hundred fifty-two adult, cooperative intensive care unit (ICU) patients were interviewed 6 months after hospital discharge about their memory of intensive care. The patient was considered to be cooperative when he/she was aware of self and environment at the interview. The patients were grouped as follows: A (45 patients) substantially no sedation, B (85) morphine, and C (22) morphine and other sedatives. RESULTS: The patients having no memory of intensive care were 38%, 34%, and 23% respectively, in the three groups. They were less ill, according to SAPS II (P <.05), and had a shorter ICU stay (P <.01). Group C patients were more seriously ill according to SAPS II, duration of mechanical ventilation, and length of stay in ICU and in hospital (P <.001). The incidence of factual, sensation, and emotional memories was not different among the three groups. Females reported at least one emotional memory more frequently than males (odds ratio 4.17; 95% CI 10.97-1.59). CONCLUSIONS: The patients receiving sedatives in the ICU are not comparable with those receiving only opiates or nothing, due to the different clinical condition. The lack of memory of intensive care is present in one third of patients and is influenced more by length of stay in ICU than by the sedation received. Sedation does not influence the incidence of factual, sensation, and emotional memories of ICU admitted patients. Females have higher incidences of emotional memories than males.

[Memory for postoperative pain six months after discharge from the hospital]. / Il ricordo del dolore postoperatorio a sei mesi dalla dimissione dall'ospedale.

OBJECTIVE: To investigate memory for postoperative pain in Intensive Care Unit (ICU) admitted patients after hospital discharge. DESIGN: Prospective study by direct interviews. METHODS: Six months after hospital discharge, we interviewed adult, postoperative, co-operative patients consecutively admitted to ICU for more than 24 hrs, resident near the hospital, who gave informed consent. We investigated intensity of postoperative pain and recollections of critical care reported by patients. The following data were collected from medical records: type and duration of surgical intervention, type of anaesthesia and fentanyl dose, severity of illness at ICU admission, ICU and hospital (after ICU) length of stay and postoperative administration of morphine. RESULTS: Of 130 patients interviewed, 82 (63%) reported no pain, 27 (21%) low and 21 (16%) more than low pain. Among these 3 groups of patients, there was no statistically significant difference in all the variables collected from medical records. Patients who remembered more than low pain recorded emotional distress more frequently (p < 0.001) and physical discomfort less frequently (p < 0.01) than patients whose pain was absent or low. CONCLUSIONS: Most patients report that postoperative pain, during their ICU stay, was absent or low. Emotional distress seems to be related to memory for postoperative pain.

A gas-chromatographic determination of the ppb levels of volatile halogenated hydrocarbons in water for injections.

Some volatile halogenated hydrocarbons have been found in commercial large volume parenterals (LVPs) prepared from untreated or treated (disinfected) water. To monitor the presence of volatile halogenated hydrocarbons in the source water and also in the water for injections, a low cost and sufficiently simple procedure has been developed, specifically for the following components: 1,1,1 trichloroethane, 1,1,2 trichloroethylene, 1,1,2,2 tetrachloroethylene, carbon tetrachloride, chloroform, dichlorobromomethane and dibromochloromethane. A Head-space technique coupled with ECD-gaschromatography was used. The procedure is thoroughly discussed in the article, including the results of a ring test for a preliminary validation of this method.

Physical parameters and biological activity of sulfonamides.

The activity coefficients "gamma" aqueous solution and the diffusion rate constants (Kd) from artificial gastric and intestinal juices were measured for eleven sulfonamides; the corresponding absorption rate constants (Ki) were then calculated. The activity coefficient was correlated with various parameters, such as the n-octanol/water and isoamyl acetate/water partition coefficients, and the absorption constant. The activity coefficient "gamma" plays an important role on the global biological activity, even if partly depending upon chemical interactions. Constant ratios (about 10%) referred to solubility of the sulfonamidic compounds in the "amorphous state" were regarded as available in blood for biological activity, regardless of the respective binding with plasma proteins.

Chronotropic response of isolated atria to acid base alterations.

The effect of acid-base alterations on spontaneous rate was analysed using isolated atria exposed to cumulative degrees of acidosis produced either by adding HCl or by increasing PCO2 in the incubation medium. Frequncy vs. pH curves were made to assess chronotropic response to acid-base changes. Heart rate was increased in alkalosis and decreased when the pH of the medium was lowered. Both "respiratory" and "metabolic" alterations affected the contraction rate to the same extent. Decreasing pH from normal values seemed to decrease heart rate more than the enhancement produced by the same change in pH towards the alkalotic side. When frequency was plotted as a function of hydrogen ion activity (aH+) a more linear relationship was obtained, either with pure "metabolic" or with "respiratory" acid-base alterations. Increasing (aH+) from normal values seemed to decrease heart rate to the same extent (respiratory alterations) or even less (metabolic alterations) than the enhancement produced by the same change in (aH+) towards the alkalotic side. Neither the increase in rate produced by alkalosis nor the decrease induced by acidosis were prevented by blocking the neurotransmitters by atropine or propranolol.

[Evaluation of biological activity of organic substances by measuring the physico-chemical parameters (author's transl)]. / Valutazione delle attività biologica di sostanze organiche mediante la misura di parametri fisico-chimici.

For a particular form (amorphous phase) of physical acting substances the water solubility, in conditions very close to the in vivo ones, has been compared with corresponding biological activities. The reciprocal of the above parameter shows a good correlation with various physico-chemical, biochemical and pharmacological parameters of xanthinic compounds, analgesic alkaloids, barbiturates, sulphonamides. The solubility of the crystalline phase cannot be correlated with the biological activity: the ratio between these two solubilities shows this inability.