Lucio Torelli

Influence of prehospital treatment on the outcome of patients with severe blunt traumatic brain injury: a single-centre study

Aim, patients, and methods To compare retrospectively the outcomes of patients with severe traumatic brain injury (Injury Severity Score, ISS total ≥15; the Abbreviated ISS-head, aISShead ≥9) admitted to our Intensive Care Unit by helicopter (helicopter emergency medical service, HEMS group = 89) with those transported by ambulance (GROUND group = 105) from January 2002 to December 2007. Results The groups were comparable for age, Glasgow Coma Scale, ISS total, and aISShead. The preadmission time of the HEMS group was significantly longer as compared with the GROUND group, but the interval from admission to definitive care was significantly shorter. In the prehospital phase, HEMS patients were more aggressively treated, as indicated by a significantly greater number of procedures performed (i.e. tracheal intubation and positioning of intravenous lines) and larger volumes of fluids infused. The overall mortality was lower in the HEMS than in the GROUND patients (21 vs. 25% respectively, P<0.05). The survival with or without only minor neurological disabilities was higher in the HEMS than in the GROUND group (54 vs. 44% respectively, P<0.05); among the survivors, the rate of severe neurological disabilities was lower in the HEMS than in the GROUND group (25 vs. 31%, P<0.05). Conclusion In our experience, aggressive early treatment of patients with severe traumatic brain injury was associated with a better outcome likely because of the prevention of secondary brain injury and a shorter interval elapsing from the trauma to definitive care despite more time spent on the scene by the intervening team.

Changes in Implant Stability Using Different Site Preparation Techniques: Twist Drills versus Piezosurgery. A Single-Blinded, Randomized, Controlled Clinical Trial

PURPOSE The objective of the present investigation was to longitudinally monitor stability changes of implants inserted using traditional rotary instruments or piezoelectric inserts, and to follow their variations during the first 90 days of healing. MATERIALS AND METHODS A randomized, controlled trial was conducted on 20 patients. Each patient received two identical, adjacent implants in the upper premolar area: the test site was prepared with piezosurgery, and the control site was prepared using twist drills. Resonance frequency analysis measurements were taken by a blinded operator on the day of surgery and after 7, 14, 21, 28, 42, 56, and 90 days. RESULTS At 90 days, 39 out of 40 implants were osseointegrated (one failure in the control group). Both groups showed an initial decrease in mean implant stability quotient (ISQ) values: a shift in implant stability to increasing ISQ values occurred after 14 days in the test group and after 21 days in the control group. The lowest mean ISQ value was recorded at 14 days for test implants (97.3% of the primary stability) and at 21 days for the control implants (90.8% of the primary stability). ISQ variations with respect to primary stability differed significantly between the two groups during the entire period of observation: from day 14 to day 42, in particular, the differences were extremely significant (p < .0001). All 39 implants were in function successfully at the visit scheduled 1 year after insertion. CONCLUSIONS The findings from this study suggest that ultrasonic implant site preparation results in a limited decrease of ISQ values and in an earlier shifting from a decreasing to an increasing stability pattern, when compared with the traditional drilling technique. From a clinical point of view, implants inserted with the piezoelectric technique demonstrated a short-term clinical success similar to those inserted using twist drills.

MMP-9 Microsatellite Polymorphism and Susceptibility to Carotid Arteries Atherosclerosis

Objective—The aims of this study were to compare a microsatellite polymorphism (PM) of matrix metalloproteinase (MMP)-9 in patients with carotid atherosclerosis and control population, and to assess the relationship between this PM and plaque structure. Methods and Results—One hundred fifty patients referring to vascular diagnostic centers for suspected carotid atherosclerosis (at ultrasound examination: 110 positive, 40 negative) and controls (n=110) have been genotyped for MMP-9 PM. After controlling for risk factors, allelic and genotype frequencies were significantly different among the groups, with significant prevalence of long microsatellites in patients with carotid atherosclerosis. Long microsatellites (settled as 22 to 27 repeats) were associated with carotid atherosclerosis (odds ratio [OR], 5.2; 95% confidence interval [CI], 2.9 to 9.2), compared with controls; an independent case control study on patients with coronary atherosclerosis confirmed such result. Binary logistic regression showed that hypertension, long microsatellites in MMP-9 PM and smoking habits were variables accounting for the difference between ultrasound-positive patients and controls. Long microsatellites were also associated to plaques with thin fibrous cap and echolucent core (OR, 13.1; 95% CI, 1.6 to 100). These alleles were slightly more represented in female patients (&khgr;2 test=0.019; OR, 2.7; 95% CI, 1.2 to 6) but not associated with other risk factors. Plasma MMP-9 levels were related neither to MMP-9 PM nor to plaque type, and were related to gender and extension of atherosclerosis in carotid arteries. Conclusions—The number of repeats (≥22 CA) in the microsatellite of MMP-9 promoter, but not MMP-9 plasma levels, is associated to carotid atherosclerosis and particularly to plaques with a thin fibrous cap.

Regulation of the spatial code for BDNF mRNA isoforms in the rat hippocampus following pilocarpine-treatment: A systematic analysis using laser microdissection and quantitative real-time PCR

Brain‐derived neurotrophic factor (BDNF) is essential for neuronal survival, differentiation, and plasticity and is one of those genes that generate multiple mRNAs with different alternatively spliced 5′UTRs. The functional significance of many BDNF transcripts, each producing the same protein, is emerging. On the basis of the analysis of the four most abundant brain BDNF transcripts, we recently proposed the “spatial code hypothesis of BDNF splice variants” according to which the BDNF transcripts, through their differential subcellular localization in soma or dendrites, represent a mechanism to synthesize the protein at distinct locations and produce local effects. In this study, using laser microdissection of hippocampal laminae and reverse transcription‐quantitative real‐time PCR (RT‐qPCR), we analyzed all known BDNF mRNA variants at resting conditions or following 3 h pilocarpine‐induced status epilepticus. In untreated rats, we found dendritic enrichment of BDNF transcripts encoding exons 6 and 7 in CA1; exons 1, 6, and 9a in CA3; and exons 5, 6, 7, and 8 in DG. Considering the low abundance of the other transcripts, exon 6 was the main transcript in dendrites under resting conditions. Pilocarpine treatment induced an increase of BDNF transcripts encoding exons 4 and 6 in all dendritic laminae and, additionally, of exon 2 in CA1 stratum radiatum and exons 2, 3, 9a in DG molecular layer while the other transcripts were decreased in dendrites, suggesting restriction to the soma. These results support the hypothesis of a spatial code to differentially regulate BDNF in the somatic or dendritic compartment under conditions of pilocarpine‐induced status epilepticus and, furthermore, highlight the existence of subfield‐specific differences.

A Stable Numerical Approach for Implicit Non-Linear Neutral Delay Differential Equations

In this paper we consider implicit non-linear neutral delay differential equations to derive efficient numerical schemes with good stability properties. The basic idea is to reformulate the original problem eliminating the dependence on the derivative of the solution in the past values. Our hypothesis on the original equation allow us to study the boundedness and asymptotic stability of the true and numerical solutions by the theory of stability with respect to the forcing term.

Pulmonary embolism in critically ill patients receiving antithrombotic prophylaxis: A clinical-pathologic study

PURPOSE The true incidence of pulmonary embolism (PE) in critically ill adult patients receiving antithrombotic prophylaxis is unknown, as well as the impact on the outcome. The aim of this study was to assess the incidence of PE in a surgical and medical intensive care unit and to evaluate the presence of risk factors that could be helpful in identifying patients at higher risk of missed diagnosis. MATERIALS AND METHODS We retrospectively reviewed the autopsies and clinical data of all patients who died in our intensive care unit from 1996 to 2007. All patients received prophylaxis with subcutaneous low-molecular weight heparin. RESULTS Among the 600 autopsies, the clinical diagnosis of PE was confirmed in 13 patients (true positives) and not confirmed in 20 patients; in 73 patients, the PE was discovered only at the autopsy (false negatives [FNs]). The overall incidence of PE in our patients was 14.3%. Pulmonary embolism was considered the cause of death in 45% of FNs and 77% of true positives. Among all comorbidities, only a recent abdominal surgery and the presence of acute renal failure were associated with a higher risk of missed diagnosis. In the FN group, there was a significantly higher frequency of cases of septic shock. CONCLUSIONS Despite thromboprophylaxis, critically ill patients remain at risk for PE; and because of the difficulty in diagnosing it clinically, the death certificate diagnosis of PE underestimates the problem.

RUNGE-KUTTA METHODS FOR RETARDED FUNCTIONAL DIFFERENTIAL EQUATIONS

We introduce Runge–Kutta (RK) methods for Retarded Functional Differential Equations (RFDEs). With respect to RK methods (A, b, c) for Ordinary Differential Equations the weights vector b ∈ ℝs and the coefficients matrix A ∈ ℝs×s are replaced by ℝs-valued and ℝs×s-valued polynomial functions b(·) and A(·) respectively. Such methods for RFDEs are different from Continuous RK (CRK) methods where only the weights vector is replaced by a polynomial function. We develop order conditions and construct explicit methods up to the convergence order four.

High Prevalence of BK Polyomavirus Sequences in Human Papillomavirus-16-Positive Precancerous Cervical Lesions

High‐ and low‐grade cervical lesions were analyzed for the presence of polyomavirus (PYV) and human papillomavirus (HPV) sequences. In precancerous cervical lesions, the overall prevalence of PYV sequences was 44% (41/93). Specifically, among the PYV‐positive samples, 83% (34/41) tested positive for BK polyomavirus (BKV) sequences, whereas 17% (7/41) were positive for JC‐virus. None of the samples were positive for simian virus 40. The presence of BKV DNA in high‐grade squamous intraepithelial lesions was confirmed by in situ PCR. BKV sequences were detected more frequently in high‐grade squamous intraepithelial lesions, together with the genotype HPV‐16. The association of BKV with precancerous cervical lesions suggests that this polyomavirus participates with HPV‐16 in the cell transformation process. Alternatively, BKV might multiply better in HPV‐16‐positive cells from precancerous cervical lesions than in HPV‐16‐negative cells. J. Med. Virol. 83:1770–1776, 2011.

BUBR1 expression in oral squamous cell carcinoma and its relationship to tumor stage and survival.

Defects in the mitotic spindle checkpoint have been proposed to contribute to the chromosomal instability observed in human cancers, including oral squamous cell carcinoma (OSCC). BUBR1 is a key component of the spindle checkpoint, whose role in oral carcinogenesis still needs to be clarified.

ASSESSMENT OF A NEW MATHEMATICAL MODEL FOR THE COMPUTATION OF NUMERICAL PARAMETERS RELATED TO RENAL CORTICAL BLOOD FLOW AND FRACTIONAL BLOOD VOLUME BY CONTRAST-ENHANCED ULTRASOUND

We analyzed the value of a new mathematical model for the quantification of renal cortical blood flow and fractional blood volume by contrast-enhanced ultrasound after the injection of sulfur hexafluoride-filled microbubbles. A vessel-mimicking phantom experiment was preliminarily performed which showed that the effect of microbubble diffusion is negligible compared with the effect of liquid drag. Twelve healthy volunteers (7 male, 5 female; 27 to 48 years [n = 6; group 1], and 61 to 80 years [n = 6; group 2], respectively), with normal renal and cardiac function and not undergoing any pharmacologic treatment, were examined. In each volunteer, both kidneys were scanned after intravenous injection of sulfur hexafluoride-filled microbubbles at a slow rate (4.8 mL at a flow of 4.0 mL/min), and the refill kinetics of the renal cortex after microbubble destruction was evaluated by echo-signal intensity quantification. The progressive replenishment of the renal vessels was approximated both by standard negative exponential function and by the piecewise linear function resulting from our mathematical model. A better dataset approximation was provided by piecewise linear versus standard negative exponential function (overall mean square error: 0.44 vs. 0.51; p < 0.05, Wilcoxon test). The piecewise linear function provided a curve composed of four linear tracts (n = 3 volunteers; 2 from group 1 and 1 from group 2), three linear tracts (n = 6 volunteers; 3 from group 1 and 3 from group 2) or two linear tracts (n = 3 volunteers; 1 from group 1 and 2 from group 2). The piecewise linear function versus standard negative exponential function improved data approximation for the computation of numerical values related to renal cortical blood flow velocity and fractional blood volume.