Vascular pentraxin 3 controls arterial thrombosis by targeting collagen and fibrinogen induced platelets aggregation.

AIM: The long pentraxin PTX3 plays a non-redundant role during acute myocardial infarction, atherosclerosis and in the orchestration of tissue repair and remodeling during vascular injury, clotting and fibrin deposition. The aim of this work is to investigate the molecular mechanisms underlying the protective role of PTX3 during arterial thrombosis. METHODS AND RESULTS: PTX3 KO mice transplanted with bone marrow from WT or PTX3 KO mice presented a significant reduction in carotid artery blood flow following FeCl3 induced arterial thrombosis (-80.36±11.5% and -95.53±4.46%), while in WT mice transplanted with bone marrow from either WT or PTX3 KO mice, the reduction was less dramatic (-45.55±1.37% and -53.39±9.8%), thus pointing to a protective effect independent of a hematopoietic cell's derived PTX3. By using P-selectin/PTX3 double KO mice, we further excluded a role for P-selectin, a target of PTX3 released by neutrophils, in vascular protection played by PTX3. In agreement with a minor role for hematopoietic cell-derived PTX3, platelet activation (assessed by flow cytometric expression of markers of platelet activation) was similar in PTX3 KO and WT mice as were haemostatic properties. Histological analysis indicated that PTX3 localizes within the thrombus and the vessel wall, and specific experiments with the N-terminal and the C-terminal PTX3 domain showed the ability of PTX3 to selectively dampen either fibrinogen or collagen induced platelet adhesion and aggregation. CONCLUSION: PTX3 interacts with fibrinogen and collagen and, by dampening their pro-thrombotic effects, plays a protective role during arterial thrombosis.

BIM upregulation and ROS-dependent necroptosis mediate the antitumor effects of the HDACi Givinostat and Sorafenib in Hodgkin lymphoma cell line xenografts.

Relapsed/refractory Hodgkin's lymphoma (HL) is an unmet medical need requiring new therapeutic options. Interactions between the histone deacetylase inhibitor Givinostat and the RAF/MEK/ERK inhibitor Sorafenib were examined in HDLM-2 and L-540 HL cell lines. Exposure to Givinostat/Sorafenib induced a synergistic inhibition of cell growth (range, 70-80%) and a marked increase in cell death (up to 96%) due to increased H3 and H4 acetylation and strong mitochondrial injury. Gene expression profiling indicated that the synergistic effects of Givinostat/Sorafenib treatment are associated with the modulation of cell cycle and cell death pathways. Exposure to Givinostat/Sorafenib resulted in sustained production of reactive oxygen species (ROS) and activation of necroptotic cell death. The necroptosis inhibitor Necrostatin-1 prevented Givinostat/Sorafenib-induced ROS production, mitochondrial injury, activation of BH3-only protein BIM and cell death. Knockdown experiments identified BIM as a key signaling molecule that mediates Givinostat/Sorafenib-induced oxidative death of HL cells. Furthermore, in vivo xenograft studies demonstrated a 50% reduction in tumor burden (P<0.0001), a 5- to 15-fold increase in BIM expression (P < 0.0001) and a fourfold increase in tumor necrosis in Givinostat/Sorafenib-treated animals compared with mice that received single agents. These results provide a rationale for exploring Givinostat/Sorafenib combination in relapsed/refractory HL.

Low-dose unenhanced CT protocols according to individual body size for evaluating suspected renal colic: cumulative radiation exposures.

PURPOSE: The aim of this study was to assess the radiation dose of dose-reduced unenhanced abdominal multidetector computed tomography (MDCT) scan protocols for suspected renal colic in patients within normal weight range and overweight-obese patients and to record the cumulative dose of repeated examinations. MATERIALS AND METHODS: Over a 2-year period, we performed 1,026 unenhanced CT examinations for urolithiasis; among these, 675 were performed on 636 patients referred from the emergency department. Patients were divided into two groups on the basis of body mass index (BMI): normal weight (BMI <25 kg/m(2) group 1); overweight and obese (BMI >25 kg/m(2) group 2). For patients in group 1 and group 2, the protocols of our 64-row scanner prescribe tube current settings at 70 mAs and 150 mAs, respectively. The dose-length product (DLP) estimated by using the manufacturer's software was converted into effective dose (ED). RESULTS: Mean DLP and ED were 177 and 345 mGy/cm and 2.4 and 4.8 mSv for group 1 and group 2, respectively. A subset of 25 patients (3.7%) underwent two or more examinations, with estimated ED ranging from 4.8 to 19.2 mSv. CONCLUSIONS: Although radiation dose is nearly double in overweight-obese patients undergoing MDCT, it remains lower than that delivered by a standard-dose protocol. Patients with flank pain, who are often young, are at increased risk for serial CT examinations. Use of a low-dose protocol is mandatory in both normal-weight and obese patients to minimise radiation exposure.

[The chemical neuromodulation of pain: a review]. / La neuromodulazione chimica del dolore: una rassegna.

The chronic pain is a true emergency. In fact, the study "Pain in Europe 2005" showed that 26% of the Italian population is suffering by it. Chronic pain can be benign, when caused by a tissular damage, or malignant when cancer-related. The study of the pain has made a lot of progress in the last years. An example is the chemical neuromodulation, that interferes with the transmission of the pain afferences toward the brain, through the administration of chemical substances in the spinal or cranial compartment in well selected patients. This allows the use of doses lower than those required for other ways of administration, with less collateral effects and a more rapid response.

[Our experience in the chemical spinal neuromodulation in chronic pain from spinal collapse due to osteoporosis.]. / La nostra esperienza sulla neuromodulazione chimica spinale nel dolore cronico da collasso vertebrale di origine osteoporotica.

AIMS: Osteoporosis is a metabolic disease of the bone characterized by reduced bone mass and microstructural deterioration of bone tissue with a consequent increase in bone fragility and risk of vertebral collapse. Treatment of osteoporosis with the new molecule is effective in improving the density and quality of bone but does not provide an analgesic effect for patients with vertebral collapse. The treatment of chronic pain from vertebral collapse is difficult and may require the use of opioids, but for some patients the intake of these drugs is burdened with systemic side effects. The aim of our study is to use the way in reducing intrathecal opioid dosage and at the same time have good pain control without significant side-effects. We report our experience in the use of continuous infusion pump for intrathecal morphine in patients with chronic pain from osteoporotic vertebral collapse that can not tolerate therapy with systemic opioids because of severe side effects. MATERIALS AND METHODS: 24 patients (19 women and 5 men with average age of 73.3 years) with a diagnosis of chronic pain from vertebral collapse refractory to treatment for systemic analgesic were treated with the use of pumps for intrathecal infusion of morphine. All patients were fit the criteria for inclusion. For the measurement of pain the visual analogue scale (VAS) in three stages: T0, T1, T2 was administered to all patients. For the evaluation of the quality of life the Questionnaire of quality of life of the European Foundation for Osteoporosis (QUALEFFO) was administered in three times. RESULTS: In the one year follow-up there was a significant reduction in pain measured by VAS, from 8.5 to 1.9 in T0 to T2 in all patients. Similarly there was a reduction in the average score of QUALEFFO of all variables, from T0 equal to 114.7 to T2 equal to 79.1. With the intrathecal infusion of morphine no patient required an additional systemic treatment. CONCLUSIONS: This study demonstrates that intrathecal-morphine therapy offers patients relief from pain and a good quality of life. Continuous intrathecal infusion of morphine is a valuable therapy and is particularly suitable for those patients who show side effects with the administration of systemic opioids.

Subintimal angioplasty as the first-choice revascularization technique for infrainguinal arterial occlusions in patients with critical limb ischemia.

Our aim was to appraise the feasibility and outcomes of subintimal angioplasty (SA) for the percutaneous revascularization of infrainguinal arterial occlusions in patients with critical limb ischemia (CLI). We retrospectively assessed 117 SA procedures in 109 limbs with complete infrainguinal occlusions from 105 patients with CLI. Among these, the superficial femoral artery (SFA) was the only occluded vessel in 27 limbs, while infrapopliteal (IP) occlusions occurred in 82. Average clinical follow-up was 13.5 months (range 1-37). Outcomes were assessed according to the site of SA (SFA vs. IP) and the length of the occlusion (< vs. > or =10 cm). Univariate analyses for the rate of limb salvage and patient survival according to the Kaplan-Meier method were performed. SA-based revascularization had a success rate of 84.4% per limb (89% in SFA and 83% in IP occlusions). During follow-up 12 patients (11.3%) underwent major limb amputation, 11 (10.3%) underwent bypass surgery, and 14 (13.7%) died. Most amputations occurred in patients in whom SA had been unsuccessful and were associated with long (> or =10 cm) occlusions (p = 0.055). Clinical restenosis occurred in seven (6.6%) patients. Survival analysis showed at 6, 12, and 24 months limb salvage rates of 90%, 87%, and 85% and overall survival rates of 90%, 88%, and 83%, respectively. Complications of SA were uncommon (4.7%) and all were successfully managed percutaneously. Infrainguinal SA is an effective revascularization technique that provides a high likelihood of limb salvage and should be the first-choice strategy in the management of patients with CLI.

Short term analgesia based sedation in the Intensive Care Unit: morphine vs remifentanil + morphine.

AIM: The aim of the study was the evaluation of postoperative short term analgesia-based sedation provided by a continuous i.v. morphine vs morphine+remifentanil infusion in the ICU. METHODS: A prospective, randomized, controlled study was carried out. INCLUSION CRITERIA: patients aged > 18 years undergoing major surgery (abdominal, vascular, thoracic). A total of 100 patients undergoing balanced anaesthesia, were enrolled; at the end of surgery an i.v. loading morphine dose (0.1 mg/kg) was administered and a continuous ground i.v. infusion (0.24 microg/kg/min) was started. When the patient was admitted to the ICU, a second i.v. continuous infusion was started and patients were allocated into 2 groups with regard to the second opioid: MM = morphine + morphine, MR = morphine + remifentanil. The second continuous infusion (boluses allowed) was titrated to obtain a numerical rate score (NRS) < 3 and Ramsay Scale =or>2. If Ramsay =or< 2 rescue sedation was administered (diazepam). RESULTS: The groups were homogeneous with regard to gender, age, weight, duration of surgery, intraoperative opioids, SAPS II. The second infusion rate in the first 24 postoperative hours was 0.73+/-0.55 microg/kg/min morphine in MM and 0.06+/-0.05 microg/kg/min remifentanil in RM. Hemodynamic parameters and SpO(2) were similar. Hypnotic consumption and NRS were significantly lower in RM, while Ramsay Scale was higher. Postextubation respiratory rate and minute volume were lower in group MM, while PaCO(2), postoperative nausea and vomiting (PONV) incidence and frequency of diazepam administration were higher. In both groups more than 70% of the patients were very satisfied. CONCLUSION: The combination of morphine + remifentanil provided better analgesia and sedation than morphine alone, with a lower incidence of side effects and a similar hemodynamic profile and patient satisfaction. The adherence to a clear analgesia based sedation protocol probably represents the most important issue carrying out analgosedation; however, the continuous infusion of a short acting drug, although more expensive, allows better titration and adjustment of the desired level of analgesia and sedation, avoiding the risk of undersedation as well as oversedation with a potential reduction of otherwise unnecessary ICU stays and, consequently, a decrease in comprehensive costs.

Effect of different sterile barrier precautions and central venous catheter dressing on the skin colonization around the insertion site.

AIM: The purpose of this prospective, randomized, controlled study was the comparison of maximal sterile barrier (consisting of mask, cap, sterile gloves, gown, large drape) vs control precautions (mask, cap, sterile gloves, small drape) and of transparent polyurethan film vs gauze dressing for use on central venous (CVC) nontunneled catheters, inserted via the jugular vein. Skin colonization at the insertion site (defined by quantitative skin cultures performed at the time of insertion and in days 2 and 5) was used as a primary endpoint. Catheter tip colonization was also assessed through qualitative culture and CVC related sepsis was defined by the isolation of the same organism from the catheter tip and the blood, with clinical sepsis of no other apparent source. METHODS: Eighty-two consecutive patients were enrolled, admitted to a mixed medical-surgical ICU, aged 72+/-12 years, 58% male, SAPS II 42+/-13. One-hundred and seven CVCs were studied (presenting 750 catheter in situ days); CVCs were in place for a mean period of 6.9+/-4.7 days and 5 episodes of central catheter-related bloodstream infection were detected (6.6 per 1000 catheter days). RESULTS: A multiple logistic regression detected an increased risk of skin colonization in male gender (OR=2.5) and control precautions (OR=3.4) and no difference with regard to age, dressing and diagnostic group. CONCLUSIONS: Maximal sterile barrier proved to be an effective and recommended practice. However surveillance skin cultures revealed the common and changing nature of colonization of skin at the insertion site.

[Laryngeal mask vs tracheal tube in pediatric anesthesia in the presence of upper respiratory tract infection]. / Maschera laringea vs tubo orotracheale in anestesia pediatrica nella flogosi delle prime vie aeree.

BACKGROUND: The aim of this report is to assess the incidence of postoperative respiratory complications in patients recently suffering from inflammation of the upper respiratory tract in whom a LMA or an uncuffed orotracheal tube have been used. METHODS: Four hundred patients were enrolled aged 6 months to 12 years undergoing general anaesthesia for elective body surface surgery with insertion of the LMA (group M) or the uncuffed tube (group T). Acute inflammation of the upper airways (URI) was assessed, defined by the presence of at least two of the following symptoms, rhinorrhea, coughing, pharyngodynia, disphony, fever, malaise. The appearance of post-surgical adverse respiratory events (ARE), such as laryngospasm, stridor, disphony, excessive coughing was detected. Patients were divided into four groups in relation to the management of the airway and the presence or otherwise of URI (M URI, M NO URI, T URI, T NO URI). RESULTS: In NO URI patients, the presence of ARE was 9.6% in the M and 36.9% in the T group (p < 0.001); in URI patients, these figures were respectively 31.5% and 73.9% (p < 0.001). CONCLUSIONS: The frequency of ARE increases significantly in URI patients with both LMA and the tracheal tube, but with the former is far lower than with the latter. Despite the appearance of only minor and transient complications, it is confirmed that the tracheal intubation is an additional risk factor as a result of the mechanical airway simulation. In recent URI, it would seem appropriate to avoid tracheal intubation, if possible, preferring the LMA.

[Laryngeal mask vs tracheal intubation during mechanical ventilation in pediatric anesthesia]. / Maschera laringea vs tubo tracheale in ventilazione meccanica in anestesia pediatrica.

AIM: The aim of this study was to evaluate and compare the parameters for mechanical respiration in pediatric patients undergoing controlled ventilation with a laryngeal mask (LM) and an uncuffed orotracheal tube. METHODS: The study examined 100 ASA 1 patients undergoing general anesthesia with myoresolution and mechanical ventilation using a Servo Ventilator 900 (constant flow, 25% insufflation, 10% teleinspiratory pause, tidal volume 10 ml/kg). All patients were divided into 2 groups matched for age and weight. An uncuffed orotracheal tube was used in one group (Group T) and a laryngeal mask (LM) in the other (Group M). The following parameters were measured: peak and pause pressure in the respiratory passage (Paw), total inspiratory resistance (R tot), compliance (C) and air loss expressed as a fraction of inspired volume (Vi-Ve/Vi). The statistical analysis of results was performed using Student's "t"-test and the level of significance was p < 0.05. RESULTS: Peak pressures were comparable in the two groups and were lower than the pressure needed to open the lower esophageal sphincter. These values could be further reduced by the extension of insufflation time achieved by abolishing the teleinspiratory pause included in the study to measure air resistances and compliance. Air losses were also similar in both groups, being respectively 13 and 11%. This means that environmental pollution using LM was not greater than with the uncuffed tube and confirms that, even with the latter, the protection of the airways cannot be regarded as absolute. Total inspiratory resistances were respectively 16.1 cm H2O/l/sec in group T and 15.1 cm H2O/l/sec in group M. This occurred in spite of the fact that the latter showed an in vitro capacity to oppose lower resistances compared to the corresponding tubes given that it was shorter with a larger diameter. Studies using the mechanical model did not include the laryngeal mask--larynx connection which may cause increased resistance owing to the variable position of the epiglottis, although this cannot be identified clinically. CONCLUSIONS: The laryngeal mask allows mechanical ventilation with low pressure in the respiratory passage and reduced air losses compared to the uncuffed tracheal tube. The risk of gastroesophageal insufflation is therefore minimal and artificial ventilation is reliable, if correctly performed. Lower levels of inspiratory resistance might be an advantage in spontaneous breathing owing to the consequent reduction of respiratory effort, but they do not appear to be significantly lower than with the tracheal tube.

Beneficial effects of verapamil in renal-risk surgical patients.

OBJECTIVE: To test whether the administration of calcium channel antagonists, such as verapamil (V), on the day before, during, and for 24-36 h after an important abdominal intervention, can lower the onset of acute renal failure (ARF), mostly in renal-risk patients, such as the aged. DESIGN: Randomized, nonblinded study. SETTING: Three surgical care university departments and two intensive care units of the same hospital (S. Anna, Ferrara, Italy). PATIENTS: Thirty-five elderly patients (61-83 years old) entered the study: 18 of them were given V; 17 were not treated and were considered as controls. The two study groups were overlapping as regards age, renal risk, and surgical challenge. The patients who underwent ARF (5 in the treated group, 7 among the controls) were rejected from the study. INTERVENTIONS: V was given on the eve of surgery at a dose of 80 mg/8 h per os and then through slow infusion (5 mg/4-6 h) during the next intra- and postoperative 24-36 h. Abdominal surgery was performed owing to gastric cancer (8 cases), colorectal neoplasia (10 cases), gallstone disease (4 cases), subrenal aortic aneurysm (6 cases), and iliofemoral obstructive arteriopathy (7 cases). MEASUREMENTS: Serum creatinine (SCr) was assessed to test renal function; 24-h urinary levels of brush-border enzymes (gamma glutamyl transferase, or gGT), lysosomal enzymes (N-acetyl-beta-D-glucosaminidase, or NAG), and beta 2-microglobulin (or beta 2M) were determined at T0 (on the eve of surgery), T1 (first and second day after), and T2 (7th and 8th day after) to demonstrate possible tubule cell damage. RESULTS: In the evaluated patients (13 treated with V and 10 untreated): (a) the 24-h urinary levels of gGt and NAG persisted unchanged throughout the study in the treated patients, whereas in the controls the same indices exhibited significant (p < 0.01) increases at T1 and T2; (b) the 24-h urinary levels of beta 2M showed significant (p < 0.01) increases in both groups from T0 to T1; however, at T2 these values tended to return to normal ranges in the treated patients, whereas they continued to be elevated in the untreated group. As regards the patients who underwent postoperative ARF, in the treated group urine output was significantly larger (p < 0.01 at T1 and p < 0.001 at T2), SCr was significantly (p < 0.05) lower, and the renal function recovered earlier (within 10 +/- 3 vs. 22 +/- 9 days) than in the controls. CONCLUSIONS: The administration of calcium channel antagonists to renal-risk patients during surgery and immediately before and after it has failed to prevent the onset of postoperative ARF. Nevertheless this procedure has been shown to somehow reduce surgery-mediated lesions of the tubule cells, as demonstrated by the finding of elevated urinary enzymes only in the untreated group.

[Low T3 syndrome (3,3',5-triiodothyronine) in relation to the extent of surgical trauma]. / La sindrome da basso T3 (3,3', 5-triiodotironina) in relazione all'entità del trauma chirurgico.

Thirty patients undergoing extra-thyroid surgery were divided into two groups (A and B) according to the extent of surgical stress (Group A: major surgery; Group B; minor surgery). Thyroid hormone levels were measured before the operation and up to the 3rd postoperative day in Group B and up to the 7th postoperative day in Group A. A low T3 syndrome was observed in all 30 patients examined of the first postoperative day (reduction of T3 and increase in rT3 without alterations of total thyroxin or signs of hypothyroidism) with normalisation of thyroid values by 3rd postoperative in Group B and later in Group A. The persistence of the syndrome in the latter group was due to the extent of surgical stress, the duration of anesthesia, the presence of stress factors such as staying in intensive therapy, painful symptoms and a negative energy balance during the first days following operation. This syndrome is indicative of a physiological adaptation process to reduce O2 consumption, basal metabolism and in particular protein catabolism.

[Vecuronium bromide in pediatric anesthesia]. / Bromuro di vecuronio in anestesia pediatrica.

Ninety patients were included in a study to assess the clinical characteristics of vecuronium bromide used in children. The myorelaxant was administered to all patients using different routes. The use of vecuronium at a dose approximately equal to 1ED95 was characterised by a duration of action sufficient to allow its use in short operations; on the other hand, it also produced a long induction-intubation interval and not optimal conditions in which to perform intubation. Conditions for intubation improved during induction via inhalation and there was a reduced induction-intubation interval compared to intravenous induction using the same dose of vecuronium. A further reduction in intubation time was obtained by increasing the dose from 50 to 150 micrograms/kg-1 together with an increased clinical duration of action. The "priming principle" technique also allowed intubation time to be shortened without variations in the duration of action provided a full dose of vecuronium, 100 micrograms/kg-1, was used. However, this was also associated with a notable incidence of adverse reactions. Of the various combinations examined, the most advantageous association of pre-dose and interval between doses was the association of a pre-dose of 10 micrograms/kg-1 and an interval of 4 min between doses. Lower doses countered the advantages of priming, whereas higher doses resulted in an increased number of adverse reactions without producing notable changes in the intubation time.

[Percutaneous subtotal splenic embolization in thalassemia major. A 4-year follow up]. / Embolizzazione splenica subtotale per via percutanea nella talassemia maior. Risultati a quattro anni di distanza.

Ten young patients affected with thalassemia major with hypersplenism were treated with subtotal percutaneous embolization. Percutaneous procedure was used to correct hypersplenism, while preserving a small portion of splenic parenchyma. Embolization was successful in 9 patients, and no significant complications were observed; in 1 patient arterial catheterization and splenic embolization were not possible due to splenic artery tortuosity. Post-procedural clinical course was characterized by intense pain, not always reduced by therapy. Hospitalization time was similar to that of surgical splenectomy. Effectiveness of percutaneous embolization was evaluated with splenic scintigraphy, clearance of erythrocytes marked with 99mTc and denatured with BMHP and with the analysis, both before and after percutaneous procedure, of the following 3 parameters: annual blood consumption, behavior of pre-transfusional hemoglobin, and transfusional pause. Six patients underwent a 4-year follow-up. In all cases scintigraphy showed the effectiveness of subtotal embolization, and clearance of erythrocytes appeared slower than before. As for clinics, an improvement was observed in transfusional parameters. The results from our series, though numerically limited, support the role of percutaneous splenic embolization as an alternative to surgical splenectomy in high risk patients or in patients who refuse surgery.

[Postoperative biliary calculosis: our experience with therapeutic strategy]. / La calcolosi biliare post-chirurgica: nostra esperienza in tema di strategia terapeutica.

The Authors report their experience in the treatment of 92 cases of post-surgical biliary tract stones: 17 early cases (18.5%) were treated by percutaneous nonsurgical extraction (10 cases) or by operative procedures (7 cases); 75 late cases (81.5%) were surgically treated. The Authors summarize the results of the treatment, discussing advantages and disadvantages of the various techniques.

[Advantages of a light-equipped angiographic guide in percutaneous obliteration of the spermatic veins]. / Vantaggi della guida angiografica dotata di lume nell'obliterazione percutanea delle vene spermatiche.

Percutaneous transvenous treatment has become the elective therapy for varicocele because it is a simple, safe, economic and reliable procedure. The presence of proximal anastomoses connecting a competent valved spermatic trunk with the renal vein can be responsible for a varicocele and make its treatment difficult. In such cases; the valve of the spermatic venous trunk can be bypassed using an open-ended guidewire with a removable mandril core, and then injecting the sclerosing agent through the guide. Moreover, the guidewire can facilitate the insertion of the catheter through the competent valve, thus allowing the placement of Gianturco coils. During the past 12 months we have successfully treated 4 patients affected by varicocele with competent valved venous trunk using the open-ended guidewire.

[Percutaneous nephrostomy. A 5-year experience]. / Nefrostomia percutanea. Cinque anni di esperienza.

The authors report their experience with percutaneous nephrostomy in the treatment of acute renal failure due to ureteral obstruction. One hundred and forty-three patients were treated with the positioning of 218 percutaneous nephrostomy catheters under fluoroscopic guidance. If performed as soon as possible, this percutaneous diversion provides a rapid improvement in renal function and allows an accurate staging of the lesion, as well as correct therapeutic indications. In many cases of urinary obstruction interventional radiology procedures represent a valid and successful alternative to more invasive palliative surgery.