Pamidronate Treatment of Osteonecrosis of the Hip in Young Male.

BACKGROUND: Aseptic osteonecrosis of the hip is a clinical entity in which the necrotic process of the bone leads to pain and progressive disability. OBJECTIVE: Pamidronate seems to reduce drastically the activation of the osteoclasts so that it can be useful only in the early stage of the disease, delaying the time of bone collapsing. METHOD: A 27-years-old male was treated with pamidronate for three consecutive days every four weeks. RESULTS: After three months the patient came back at control showing a marked improvement in clinical condition, referred full recover from pain and dysmotility with improvement of the quality of life, which was confirmed by the result of MRI he had for control. CONCLUSION: We reported a case of aseptic osteonecrosis of the hip which was successfully treated pamidronate at dosage of 45 mg.

High levels of serum sclerostin and DKK1 in a case of Klippel-Trénaunay syndrome.

Klippel-Trénaunay syndrome (KTS) is described as a complex syndrome characterized by various combinations of capillary, venous, and lymphatic malformations associated with bone and soft tissue hypertrophy. We report a case of a 67-year-old postmenopausal Caucasian women with KTS that shows elevated levels of sclerostin and Dickkopf-related protein 1 (DKK1). Dual-energy X-ray absorptiometry (DXA) BMD T-scores at lumbar spine and femur were normal. Serum calcium and phosphorus levels were consistently normal, 25-hydroxyvitamin D (25OHD) < 30 ng/mL, and normal parathyroid hormone (PTH). Turnover markers (serum osteocalcin [OCN], and carboxy-terminal cross-linking telopeptide of type 1 collagen [CTx]) were in the reference limits. It is interesting to note that the serum levels of sclerostin and DKK-1 were significantly higher in our patient with KTS than in a healthy volunteer (control), without impact on bone mineral density and bone formation markers. In fact, in our patient, the BMD at lumbar spine and femur was normal, and osteocalcin was not suppressed. Based on what is known, we would have expected to find low levels of the inhibitors of the Wnt system, perhaps we can explain the data as a response to the compensation for ß-catenin hyper-transformation.

Evaluation of the threshold value for the modified early warning score (MEWS) in medical septic patients: a secondary analysis of an Italian multicentric prospective cohort (SNOOPII study).

BACKGROUND: Due to aging and resources limitation, septic patients are often admitted to medical wards (MWs). Early warning deterioration is a relevant issue in this setting. Unfortunately, a suitable prognostic score has not been identified, yet. AIM: To explore the ability of Modified Early Warning Score (MEWS) to predict the in-hospital mortality in septic patients admitted to MWs. DESIGN: Secondary analysis of a multicentric prospective study. METHODS: Consecutive septic patients with positive blood culture admitted to 31 Italian MWs were included. Baseline characteristics, clinics, isolates, rate of transfer to ICU, MEWS was collected on admission according to the study protocol. The accuracy of MEWS in predicting the in-hospital mortality was assessed with the area under the receiver-operating characteristic curves. Sensitivity, specificity, positive and negative predictive value (PPV and NPV), likelihood ratio (LR) were calculated for different MEWS cut-offs and age/comorbidities subgroups. RESULTS: In total 526 patients were included in this analysis. Median MEWS was (range 0-11). In-hospital mortality was 14.8% and transfer to ICU 1.3%. Mortality progressively increased according to MEWS (3% in MEWS 0 vs. 27% in MEWS >5; Chi square for trend P < 0.05). The AUC of MEWS in predicting in-hospital mortality was 0.596 (95% CI, 0.524, 0.669). MEWS did not appear to have an adequate sensitivity, sensibility, PPV, NPV and LR both in the whole population and in the pre-specified subgroups. CONCLUSIONS: Our findings do not seem to support the use of MEWS to predict the in-hospital mortality risk of sepsis in MWs.

Subcutaneous administration of tocilizumab is effective in myointimal hyperplasia remodelling in refractory Takayasu arteritis.

Takayasu arteritis (TA) is a chronic inflammatory disease of unknown origin that involves large and mediumsized arteries, primarily the aorta and its major branches. TA is a therapeutic challenge because corticosteroids and conventional immunosuppressive agents are not always effective or safe. Interleukin 6 (IL-6) has emerged as a key cytokine in the pathogenesis of TA and its serum levels have been shown to well correlate with disease activity. We report a 19 years old female patient with TA refractory to conventional immunosuppressive agents, successfully treated with subcutaneous tocilizumab, a humanized monoclonal antibody against IL-6 receptor, in which ultrasonography (US) was used as imaging tool to follow up the patient. Currently, clinical indices of disease activity, inflammatory markers, carotid intima media thickness (cIMT) as well as carotid pulse wave velocity (cPWV) normalised, while the prednisone dosage has been tapered. Tocilizumab appears to be a good option in refractory TA, with a remarkable steroid-sparing effect. In addition, it seems to have a favourable effect on endothelial function, as it improved cIMT and PWV.

Biglycan expression in current cigarette smokers: a possible link between active smoking and atherogenesis.

OBJECTIVE: Cigarette smokers present early signs of vascular damage and systemic inflammation. Biglycan (BGN), an ubiquitous component of extracellular matrix orchestrating several physiological functions, has recently been indicated as a major source of low-density lipoprotein retention in the normal arterial intima-media layer. We evaluated whether BGN-mRNA expression was enhanced in peripheral monocytes of smokers with no additional cardiovascular risk factors (CVRFs), and if it was associated with altered carotid arterial stiffness (AS) or intima media thickness (cIMT). We also evaluated plasma markers of systemic and vascular inflammation, and correlation with BGN-mRNA. METHODS: Two-hundred-fifty-one young smokers were enrolled, with no additional CVRFs, and 60 controls. Plasma lipids, fibrinogen, C-reactive protein (CRP), interleukin-6 (IL-6), AS and cIMT were assessed. A smoke exposure index (SEIx) was calculated. RESULTS: Fibrinogen, CRP, AS indices, cIMT, and BGN-mRNA were higher in smokers compared to controls; HDL-C levels were lower, no difference was detected in IL-6 levels. After stratification of smokers in quartiles based on SEIx values, smokers in the highest quartiles presented highest fibrinogen, CRP, AS, cIMT, BGN, and also IL-6 values, and lowest HDL-C. CONCLUSION: BGN-mRNA was enhanced in young smokers, compared to controls, and appears associated to a proatherogenic profile, characterized by increased fibrinogen, CRP, and IL-6, lower HDL-C, altered AS and cIMT values, particularly in those with higher SEIx: the more cigarettes smoked over years, the more marked the alterations. Although we cannot state whether BGN have a direct causal role in inducing, maintaining and developing vascular damage, including intima-media wall thickening and arterial stiffening, our data could suggest that it may represent a link between proatherogenic status induced by cigarette smoking, and the development and progression of vascular damage.

Circulating progenitor cells in hypertensive patients with different degrees of cardiovascular involvement.

We investigated whether different degrees of hypertension-related cardiovascular involvement are associated with changes in circulating proangiogenic hematopoietic cell (PHC) numbers and/or phenotypes and/or in the PHC redox system in hypertensive individuals with isolated arterial stiffening (AS) hypertensives or with both carotid intima-media thickening and left ventricular hypertrophy (LVH) hypertensives. We also evaluated microRNA (miRs) 221 and 222 (miRs221/222) expression in CD34+ cells, the relationship between these miRs and cell number and reactive oxygen species (ROS) levels, and the expression of manganese superoxide dismutase (MnSOD), catalase (CAT) glutathione peroxidase type-1 (GPx-1) and gp91phox-containing nicotinamide-adenine-dinucleotide-phosphate-oxidase (NOX2). Proangiogenic hematopoietic cells (PHCs) from hypertensive patients and controls were isolated by flow cytometry. PHCs were higher in hypertensives than in controls but were lower in LVH than in AS hypertensives. In CD34+ cells from AS hypertensives, NOX2, MnSOD, CAT and GPx-1 were overexpressed; ROS, miRs and NOX2 were also increased and were associated with cell number. In LVH, we found an imbalance in the cell redox system; MnSOD showed the highest values, whereas CAT and GPx-1 were lower than in AS hypertensives. Intracellular ROS, miRs and NOX2 were higher and inversely associated with cell number. In AS hypertensives, the redox balance may sustain the increase in PHCs; by contrast, in hypertensives with more advanced lesions, redox imbalance may result in increased oxidative stress and cell reduction.

Circulating progenitor cells in rheumatoid arthritis: association with inflammation and oxidative stress.

OBJECTIVES: To evaluate the association between inflammation, oxidative stress, and circulating progenitor cell (CPC) number and redox equilibrium, vascular lesions and accelerated atherosclerosis in rheumatoid arthritis (RA). METHOD: Circulating CD34+ cells were isolated from 33 RA patients and 33 controls. Reactive oxygen species (ROS) levels and mRNA expression of manganese superoxide dismutase (MnSOD), catalase (CAT), glutathione peroxidase type 1 (GPx-1) antioxidant enzymes, and the gp91phox-containing nicotinamide adenine dinucleotide phosphate (NADPH) oxidase NOX2 were measured in CD34+ cells. C-reactive protein (CRP), fibrinogen, erythrocyte sedimentation rate (ESR), carotid intima-media thickness (cIMT), and arterial stiffness (AS) were also evaluated. We investigated the relationships between inflammatory markers, vascular parameters, cell number, and antioxidant enzymes. RESULTS: CD34+ cell number was lower in RA patients than in controls. In CD34+ cells from RA patients, ROS levels, MnSOD mRNA, and NOX2 mRNA were higher, while mRNA expression of GPx-1 and CAT was significantly lower. The AS, pulse wave velocity (PWV), and augmentation index (AIx) were higher, as was cIMT. CD34+ cell number was inversely correlated with CRP, ROS, PWV, and AIx, and with the CAT/MnSOD and GPx-1/MnSOD ratios. CRP was correlated with MnSOD mRNA, PWV, and AIx but not with CAT and GPx-1 mRNA. CONCLUSIONS: Our data show a link between inflammation, oxidative stress, and the impairment of the antioxidant system of CPCs and their number, and with arterial stiffness in RA subjects. This could suggest a perspective on the accelerated development of vascular damage and atherosclerosis in RA.

Topical oropharyngeal vancomycin to control methicillin-resistant Staphylococcus aureus lower airway infection in ventilated patients.

AIM: Topical vancomycin applied to the oropharynx has been shown to control carriage and lower airway infection due to methicillin-resistant Staphylococcus aureus (MRSA). We undertook a three-year prospective observational study to evaluate the effectiveness of two policies for topical vancomycin administration on oropharyngeal carriage and lower airway infection due to MRSA in patients requiring mechanical ventilation. METHODS: All consecutive patients aged over 18 years and expected to require mechanical ventilation for more than 72 hours were enrolled. During period one, patients who were established MRSA carriers received 1 g of 4% vancomycin gel into the oropharynx four times a day until carriage was abolished. During period two, all enrolled patients received the same protocol immediately on admission, irrespective of their MRSA carrier state. RESULTS: One hundred ninety-one patients met the entry criteria (98 in period one and 93 in period two). During period one, 40 patients developed oropharyngeal MRSA carriage; of these, 29 acquired MRSA in the unit. In contrast, MRSA carriage was not demonstrated during period two (relative risk [RR] 0.018, 95% confidence interval [CI] 0-0.29; P=0.004). Twenty-one patients from period one suffered from an Intensive Care Unit-acquired lower airway infection due to MRSA, compared with five patients from period two (RR 0.25, 95% CI 0.10-0.64, P=0.004). Vancomycin-intermediate Staphylococcus aureus and vancomycin-resistant enterococci were not isolated. CONCLUSION: In the setting of MRSA endemicity, the prevention of MRSA carriage by topical oropharyngeal vancomycin was more effective in reducing carriage and infection of the lower airways than treatment of established carriers.

Prevalence of virulence-associated genotypes of Helicobacter pylori and correlation with severity of gastric pathology in patients from western Sicily, Italy.

In a bacterium like Helicobacter pylori, which is characterized by a recombinant population structure, the associated presence of genes encoding virulence factors might be considered an expression of a selective advantage conferred to strains with certain genotypes and, therefore, a potentially useful tool for predicting the clinical outcome of infections. However, differences in the geographical and ethnic prevalence of the H. pylori virulence-associated genotypes can affect their clinical predictive value and need to be considered in advance. In this study we carried out such an evaluation in a group of patients living in Sicily, the largest and most populous island in the Mediterranean Sea. cagA, vacA, babA2, hopQ, oipA, sabA, and hopZ were the H. pylori virulence-associated genes assayed; their presence, expression status or allelic homologs were detected in H. pylori DNA samples and/or isolated strains, obtained by gastric biopsy from 90 Sicilian patients with chronic gastritis, inactive (n = 37), active (n = 26), or active with peptic ulcer (n = 27). Genotypes cagA (+), vacAs1, vacAm1, babA2 (+), and hopQ I, I/II were identified in 51.8, 80.4, 35.2, 47.3, and 67.7% of the different samples respectively. Only these genotypes were associated with each other and with the active form of chronic gastritis, irrespective of the presence of a peptic ulcer. In our isolates their prevalence was more similar to values observed in the north of Italy and France than to those observed in Spain or other Mediterranean countries that are closer and climatically more similar to western Sicily.

The Competency-Based Training in Intensive Care Medicine in Europe (CoBaTrICE) Italian collaborative: national results from the Picker survey.

BACKGROUND: The aim of the Competency-Based Training in Intensive Care Medicine in Europe (CoBaTrICE) project is to create an internationally acceptable competency-based training program for specialists in intensive care medicine. The CoBaTrICE Project has performed a survey, in collaboration with the Picker institute, United Kingdom, to identify desirable characteristics of Intensive Care Unit (ICU) specialists, as expressed by patients and their relatives. METHODS: A questionnaire was developed to assess 21 elements of professional competence. Each element was assigned to one of four categories of a Likert scale: 1=essential; 2=very important; 3=not too important; 4=does not matter. The results were dichotomized into essential (score: 1) and not essential (scores: 2-4) categories. Further, the documents were related to three key concepts: "medical skills and competencies", "communication with patients", and "communication with relatives". Questionnaire statements grouped by theme were also ranked for each item using a number: 1=highest rank; 21=lowest rank. Free text responses were also invited. RESULTS: Ten Italian ICUS were enrolled in the study. There were 249 questionnaires completed (18% total return rate). CONCLUSION: Priority in Italy was given to medical skills and competence. Involvement of patients and relatives in decision-making processes were among the items considered least important. Italian families preferred a paternalist approach to the end of life decision-making process.

Impact of selective decontamination of the digestive tract on carriage and infection due to Gram-negative and Gram-positive bacteria: a systematic review of randomised controlled trials.

Meta-analyses of randomised controlled trials of selective digestive decontamination have clinical outcome measures, mainly pneumonia and mortality. This meta-analysis has a microbiological endpoint and explores the impact of selective digestive decontamination on Gram-negative and Gram-positive carriage and severe infections. We searched electronic databases, Cochrane Register of Controlled Trials, previous meta-analyses and conference proceedings with no language restrictions. We included randomised controlled trials which compared the selective digestive decontamination protocol with no treatment or placebo. Three reviewers independently applied selection criteria, performed the quality assessment and extracted the data. The outcome measures were carriage and severe infection due to Gram-negative and Gram-positive bacteria. Odds ratios were pooled with the random effect model. Fifty-four randomised controlled trials comprising 9473 patients were included; 4672 patients received selective digestive decontamination and 4801 were controls. Selective digestive decontamination significantly reduced oropharyngeal carriage (odds ratio [OR] 0.13, 95% confidence interval [CI] 0.07 to 0.23), rectal carriage (OR 0.15, 95% CI 0.07 to 0.31), overall infection (OR 0.17, 95% CI 0.10 to 0.28), lower respiratory tract infection (OR 0.11, 95% CI 0.06 to 0.20) and bloodstream infection (OR 0.35, 95% CI 0.21 to 0.67) due to Gram-negative bacteria. Reduction in Gram-positive carriage was not significant. Gram-positive lower airway infections were significantly reduced (OR 0.52, 95% CI 0.34 to 0.78). Gram-positive bloodstream infections were not significantly increased (OR 1.03, 95% CI 0.75 to 1.41). The association of parenteral and enteral antimicrobials was superior to enteral antimicrobials in reducing carriage and severe infections due to Gram-negative bacteria. This meta-analysis confirms that selective digestive decontamination mainly targets Gram-negative bacteria; it does not show a significant increase in Gram-positive infection.

Prediction of successful defibrillation in human victims of out-of-hospital cardiac arrest: a retrospective electrocardiographic analysis.

In the present study we sought to examine the efficacy of an electrocardiographic parameter, 'amplitude spectrum area' (AMSA), to predict the likelihood that any one electrical shock would restore a perfusing rhythm during cardiopulmonary resuscitation in human victims of out-of-hospital cardiac arrest. AMSA analysis is not invalidated by artefacts produced by chest compression and thus it can be performed during CPR, avoiding detrimental interruptions of chest compression and ventilation. We hypothesised that a threshold value of AMSA could be identified as an indicator of successful defibrillation in human victims of cardiac arrest. Analysis was performed on a database of electrocardiographic records, representing lead 2 equivalent recordings from automated external defibrillators including 210 defibrillation attempts from 90 victims of out-of-hospital cardiac arrest. A 4.1 second interval of ventricular fibrillation or ventricular tachycardia, recorded immediately preceding the delivery of the shock, was analysed using the AMSA algorithm. AMSA represents a numerical value based on the sum of the magnitude of the weighted frequency spectrum between two and 48 Hz. AMSA values were significantly greater in successful defibrillation (restoration of a perfusing rhythm), compared to unsuccessful defibrillation (P < 0.0001). An AMSA value of 12 mV-Hz was able to predict the success of each defibrillation attempt with a sensitivity of 0.91 and a specificity of 0.97. In conclusion, AMSA analysis represents a clinically applicable method, which provides a real-time prediction of the success of defibrillation attempts. AMSA may minimise the delivery of futile and detrimental electrical shocks, reducing thereby post-resuscitation myocardial injury.

Pharmacological induction of heme oxygenase-1 inhibits iNOS and oxidative stress in renal ischemia-reperfusion injury.

Nitric oxide (NO), produced by nitric oxide synthase, is implicated in the pathophysiology of renal ischemia/reperfusion (I/R) injury. This study sought to elucidate the impact of pharmacological induction of heme oxygenase-1 (HO-1) on renal I/R injury. Rats were subjected to 45 minutes of renal ischemia followed by various times of reperfusion (30 minutes, 1 hour, or 3 hours). Plasma from sacrificed rats was obtained, and the kidneys processed for the expression of iNOS, cleaved caspase-3, p38MAPK and for immunohistochemical analysis. Furthermore, we determined renal and plasma levels of lipid hydroperoxides, total thiol groups, and plasmatic NO2-/NO3- formation. Our results showed a time-dependent increase in iNOS expression, which was also confirmed by increased plasma formation of NO2-/NO3-. Interestingly, this effect was reversed by pretreatment (12 hours) with SnCl2, a potent and specific inducer of renal HO-1 expression and activity, or by intraperitoneal injection of biliverdin (10 mg/kg). Furthermore, we observed a concomitant reduction in plasma and renal LOOH formation, a normalization of renal total thiol content, a reduction of caspase-3-mediated apoptosis, and a significant increase in p38MAPK phosphoration. Taken together, these results suggested that HO-1 and its byproduct biliverdin play major roles in the pathophysiological cascade leading to renal I/R injury.

Selective decontamination of the digestive tract reduces bacterial bloodstream infection and mortality in critically ill patients. Systematic review of randomized, controlled trials.

A systematic review and meta-analysis of randomized controlled trials (RCTs) of selective decontamination of the digestive tract (SDD) was undertaken to evaluate the impact of this procedure on bacterial bloodstream infection and mortality. Data sources were Medline, Embase, Cochrane Register of Controlled Trials, previous meta-analyses, and conference proceedings, without restriction of language or publication status. RCTs were retrieved that compared oropharyngeal and/or intestinal administration of antibiotics as part of the SDD protocol, with or without a parenteral component, with no treatment or placebo in the controls. The three outcome measures were patients with bloodstream infection, causative micro-organisms, and total mortality. Fifty-one RCTs conducted between 1987 and 2005, comprising 8065 critically ill patients were included in the review; 4079 patients received SDD and 3986 were controls. SDD significantly reduced overall bloodstream infections [odds ratio (OR), 0.73; 95% confidence interval (CI), 0.59-0.90; P=0.0036], gram-negative bloodstream infections (OR, 0.39; 95% CI, 0.24-0.63; P<0.001) and overall mortality (OR, 0.80; 95% CI, 0.69-0.94; P=0.0064), without affecting gram-positive bloodstream infections (OR, 1.06; 95% CI, 0.77-1.47). The subgroup analysis showed an even larger impact of SDD using parenteral and enteral antimicrobials on overall bloodstream infections, bloodstream infections due to gram-negative bacteria and overall mortality with ORs of 0.63 (95% CI, 0.46-0.87; P=0.005), 0.30 (95% CI, 0.16-0.56; P<0.001), and 0.74 (95% CI, 0.61-0.91; P=0.0034), respectively. Twenty patients need to be treated with SDD to prevent one gram-negative bloodstream infection and 22 patients to prevent one death.