Roberto Sorge

Assessment of metabolic brain damage and recovery following mild traumatic brain injury: a multicentre, proton magnetic resonance spectroscopic study in concussed patients

Concussive head injury opens a temporary window of brain vulnerability due to the impairment of cellular energetic metabolism. As experimentally demonstrated, a second mild injury occurring during this period can lead to severe brain damage, a condition clinically described as the second impact syndrome. To corroborate the validity of proton magnetic resonance spectroscopy in monitoring cerebral metabolic changes following mild traumatic brain injury, apart from the magnetic field strength (1.5 or 3.0 T) and mode of acquisition, we undertook a multicentre prospective study in which a cohort of 40 athletes suffering from concussion and a group of 30 control healthy subjects were admitted. Athletes (aged 16-35 years) were recruited and examined at three different institutions between September 2007 and June 2009. They underwent assessment of brain metabolism at 3, 15, 22 and 30 days post-injury through proton magnetic resonance spectroscopy for the determination of N-acetylaspartate, creatine and choline-containing compounds. Values of these representative brain metabolites were compared with those observed in the group of non-injured controls. Comparison of spectroscopic data, obtained in controls using different field strength and/or mode of acquisition, did not show any difference in the brain metabolite ratios. Athletes with concussion exhibited the most significant alteration of metabolite ratios at Day 3 post-injury (N-acetylaspartate/creatine: -17.6%, N-acetylaspartate/choline: -21.4%; P < 0.001 with respect to controls). On average, metabolic disturbance gradually recovered, initially in a slow fashion and, following Day 15, more rapidly. At 30 days post-injury, all athletes showed complete recovery, having metabolite ratios returned to values detected in controls. Athletes self-declared symptom clearance between 3 and 15 days after concussion. Results indicate that N-acetylaspartate determination by proton magnetic resonance spectroscopy represents a non-invasive tool to accurately measure changes in cerebral energy metabolism occurring in mild traumatic brain injury. In particular, this metabolic evaluation may significantly improve, along with other clinical assessments, the management of athletes suffering from concussion. Further studies to verify the effects of a second concussive event occurring at different time points of the recovery curve of brain metabolism are needed.

Short-term treatment with atorvastatin reduces platelet CD40 ligand and thrombin generation in hypercholesterolemic patients

BACKGROUND Soluble CD40L (sCD40L), a substance that maximally reflects in vivo platelet activation, is increased in patients with hypercholesterolemia. We investigated the relation between sCD40L and platelet CD4OL in hypercholesterolemic patients before and after a short-term treatment with atorvastatin. METHODS AND RESULTS Collagen-induced platelet CD40L and plasma levels of sCD40L and prothrombin fragment F1+2, a marker of thrombin generation, were investigated in 30 hypercholesterolemic patients and 20 healthy subjects. Hypercholesterolemic patients were then randomized to either diet (n=15; group A) or atorvastatin 10 mg/d (group B); the aforementioned variables were measured at baseline and after 3 days of treatment. Compared with referents, hypercholesterolemic patients showed higher values of platelet CD40L (P<0.005), sCD40L (P<0.005), and F1+2 (P<0.003). Platelet CD40L was significantly correlated with sCD40L (P<0.001), and the latter was significantly correlated with F1+2 (P<0.001). The intervention trial showed no changes in group A but a significant decrease in platelet CD40L (P<0.01), sCD40L (P<0.002), and F1+2 (P<0.03) in group B. In vitro studies demonstrated that cholesterol enhanced platelet CD40L and CD40L-mediated clotting activation by human monocytes; also, atorvastatin dose-dependently inhibited platelet CD40L expression and clotting activation by CD40L-stimulated monocytes. CONCLUSIONS This study shows that, in hypercholesterolemia, platelet overexpression of CD40L may account for enhanced plasma levels of sCD40L and F1+2. Atorvastatin exerts a direct antithrombotic effect via inhibition of platelet CD40L and CD40L-mediated thrombin generation, independently of its cholesterol-lowering effect.

Long-term outcomes of stapled hemorrhoidopexy vs conventional hemorrhoidectomy: a meta-analysis of randomized controlled trials

OBJECTIVES To assess the long-term results of stapled hemorrhoidopexy (SH) compared with conventional hemorrhoidectomy (CH) and to define the role of SH in the treatment of hemorrhoids. DATA SOURCES Published randomized controlled trials of CH vs SH with a minimum clinical follow-up of 12 months were searched and selected in the MEDLINE, EMBASE, and Cochrane Library databases using the keywords hemorrhoid, stapl, and anopexy, without language restrictions. STUDY SELECTION Potentially relevant studies were identified by the title and the abstract, and full articles were obtained and assessed in detail. DATA EXTRACTION Studies were scored according to the presence of 3 key methodologic features of randomization, blinding, and accountability of all patients, including withdrawals, and the scores ranged from 0 to 5. Studies that received a score from 3 to 5 were considered high-quality studies, whereas those with a score of 2 or less were considered of low quality. A specifically designed data form was used to collect all relevant data, including details of the experimental design, patient demographics, technical aspects, outcome measures, and complications. DATA SYNTHESIS Fifteen articles met the inclusion criteria for a total of 1201 patients. Outcomes at a minimum of 1 year showed a significantly higher rate of prolapse recurrences in the SH group (14 studies, 1063 patients; odds ratio, 5.5; P < .001) and patients were more likely to undergo further treatment to correct recurrent prolapses compared with the CH group (10 studies, 824 patients; odds ratio, 1.9; P = .02). CONCLUSION Stapled hemorrhoidopexy is a safe technique for the treatment of hemorrhoids but carries a significantly higher incidence of recurrences and additional operations compared with CH. It is the patients choice whether to accept a higher recurrence rate to take advantage of the short-term benefits of SH.

Nanocrystalline silver: a systematic review of randomized trials conducted on burned patients and an evidence-based assessment of potential advantages over older silver formulations.

The aim of this meta-analysis was to collect data from randomized trials in burn patients and to analyze them with a meta-analytic approach to give a clear message of potential advantages of nanocrystalline silver (NC) versus older silver formulations (SS).A review of all-English prospective randomized trials that compared NC versus silver sulfadiazine or silver nitrate was conducted. Primary outcome was the evaluation of differences in the infection rate of burns. Secondary outcomes were the eventual differences in the pain experienced during medications, the length of hospitalization (LOS) and costs.Five articles that met the inclusion criteria were selected (n = 285 patients). The NC group had a significant lower incidence of infections compared with the SS group (9.5% vs. 27.8%, odds ratio: 0.14 [95% CI: 0.06–0.35]; &khgr;2 test, P < 0.001), with a 2.9-fold decrease of the risk. Not all studies investigated the pain during change of dressings, LOS and costs. However, when data were available, these showed lower costs (US

Body composition during normal pregnancy: reference ranges

1533 per patient for the SS group and US

Wound infections in aesthetic abdominoplasties: the role of smoking.

946 per patient for the NC group) and decreased pain values in the NC group (Hedges’ G: −1.44 [95% CI: −1.86/−1.01]; P < 0.0001), while contrasting results were obtained for LOS.Nanocrystalline silver is a relatively new product with a significant stronger antimicrobial activity compared with older formulations. Its long lasting properties reduce dressing change frequency and are probably responsible for the decreased pain and the minor costs experienced.

Oxidative stress‐mediated platelet CD40 ligand upregulation in patients with hypercholesterolemia: effect of atorvastatin

Abstract.Maternal body composition undergoes a deep adaptative change during the course of pregnancy. Fat mass, fat-free mass, and total body water (TBW) increase in different ways and their effects on pregnancy outcome represent a field of major interest in perinatal medicine. The aim of this study was to evaluate the changes in maternal body composition [maternal weight, TBW, intracellular water (ICW) and extracellular water (ECW)] during healthy pregnancy by using bioimpedance analysis (BIA). A total of 170 healthy pregnant women, aged 22–44 years, volunteered to participate in our study. The BIA measurements were carried out with a Tefal BIA scale determining resistance and reactance. Lukaski’s multiple-regression equation was used to estimate TBW and ICW and ECW were computed using the prediction formula of Segal. The evaluations were performed at 10–38 weeks’ gestation, every 3–4 weeks, and hematocrit was determined at every time interval. Analysis of variance and multiple comparisons of Bonferroni were performed to compare variables among the different study intervals. Second-order polynomial interpolation was used to obtain percentile values for each bioimpedance parameter. Percentile bioimpedance values of the healthy population are provided at each study time, by showing the mean value and the 5th, 25th, 75th, 95th percentiles. Moreover, normal reference ranges for TBW are provided for each gestational age, in relation to maternal weight gain. Reactance, TBW, and ICW enhance slightly during the course of gestation. Tetrapolar BIA could be an easy and practical tool for evaluating changes of maternal body components during pregnancy. It could also provide indirect proof of the normal hemodilution occurring in normal pregnancies. Moreover, fat mass deposition, and not only fluid retention, seems to be responsible for the mother’s gestational weight gain, since reactance is an indirect parameter in estimating fat mass amount.

The influence of BMI, smoking, and age on vaginal erosions after synthetic mesh repair of pelvic organ prolapses. A multicenter study

Background: In this prospective study, the authors followed patients who underwent aesthetic abdominoplasty to determine the influence of smoking on the occurrence of postoperative wound infections. Methods: Patients who underwent aesthetic abdominoplasty were considered eligible for the study. The authors excluded postbariatric patients, those with ongoing clinical infections, those receiving a recent antibiotic course, and those with systemic diseases such as arteriosclerosis and diabetes mellitus. Smokers were advised to quit smoking at least 4 weeks before surgery. Results: Starting in February of 2004, the authors enrolled 84 patients. Postoperative infections were present in 13 patients (15.5 percent) and were superficial in 10 (77 percent). All but one occurred in smokers. These had a certain number of cigarettes smoked per day, years of smoking, and higher estimated overall number of smoked cigarettes when postoperative infections were present. The relative risk of smoking on infections was 12. A cutoff value of approximately 33,000 overall cigarettes smoked determined 3.3 percent false-positive and 0 percent false-negative rates. Conclusions: Smoking is an important issue in aesthetic surgery that needs to be accurately addressed during the preoperative interview. In the future, the analysis of smoke-related, easy-to-gather variables such as the estimated overall number of cigarettes smoked until surgery could help stratify patients according to their risk of manifesting infections.

Pulmonary embolism after combined abdominoplasty and flank liposuction: a correlation with the amount of fat removed.

Summary.  Objectives: We speculated that in patients with hypercholesterolemia CD40L overexpression could depend on low‐density lipoprotein (LDL)‐induced enhanced intraplatelet formation of O2·− and statin could reduce platelet CD40L via interference with platelet O2·− production. Background: CD40L is a protein with inflammatory and thrombotic properties. CD40L is upregulated in platelets from hypercholesterolemic (HC) patients but the underlying mechanism is unclear. Methods: Collagen‐induced platelet CD40L and platelet O2·− expression were investigated in 40 HC patients and 40 healthy subjects. HC patients were then randomized to either a diet (n = 20) (group A) or atorvastatin 10 mg day (n = 20) (group B); the above variables were measured at baseline and after 3 and 30 days of treatment. O2·− and CD40L were also measured in vitro in LDL‐treated platelets with or without nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibitor or atorvastatin added. Results: Compared with controls, HC patients showed higher values of platelet CD40L (P < 0.001) and O2·− (P < 0.001). Platelet CD40L was significantly correlated with O2·− (P < 0.001). The interventional trial showed no changes in group A and a significant and parallel decrease in platelet CD40L (P < 0.001) and O2·− (P < 0.001) in group B. In vitro studies demonstrated that LDL‐induced platelet CD40L and GP IIb/IIIa (PAC1 binding) activation via the NADPH oxidase pathway. CD40L upregulation was counteracted by atorvastatin in a dose‐dependent fashion. Conclusions: This study suggests that in patients with hypercholesterolemia platelet CD40L is upregulated via NADPH oxidase‐dependent O2·− generation. Atorvastatin downregulated CD40L with an oxidative stress‐mediated mechanism likely involving platelet NADPH oxidase, an effect that seemed to be independent of its cholesterol‐lowering action.

PDE10A and PDE10A-dependent cAMP catabolism are dysregulated oppositely in striatum and nucleus accumbens after lesion of midbrain dopamine neurons in rat: a key step in parkinsonism physiopathology.

Objective. To study the influence of body mass index (BMI), smoking, and age on the risk of vaginal erosions after mesh repair of pelvic prolapses. Design. Retrospective study. Setting. Three university and community hospitals. Population and sample. Patients that underwent mesh correction of prolapses between 2002 and 2007. Excluded were those with stress urinary incontinence, ongoing clinical infections, with a complete antibiotic course in the last six months and with systemic diseases affecting tissue oxygenation. Methods. Revision of medical notes. Main outcome measures. Risk contributions for age, smoking, and BMI on the occurrence of vaginal erosions. Results. Data were collected from 460 patients. Postoperative erosions were present in 7%. BMI greater than 30 conferred a 10.1‐fold increase in the risk of developing erosions, smoking a 3.7‐fold increase, and age greater than 60 years a 2.2‐fold increase. A cut‐off value of seven pack years was determined for smoking where the risk associated with light smokers was similar to that of non‐smokers. Conclusions. BMI, smoking, and age are important risk factors for pelvic organ prolapse surgery. Our data could be used to stratify patients according to their risk so that preventative measures can be taken in high‐risk patients.