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A Working Group coordinated by the Italian National Institute of Health (Istituto Superiore di Sanita) and the National Workers Compensation Authority (Istituto Nazionale per l’Assicurazione contro gli Infortuni sul Lavoro, INAIL) and consisting of 11 Italian scientific/professional societies involved in the fluoroscopically guided interventional practices has been established to define recommendations for the optimization of patients and staff radiation protection in interventional radiology. A summary of these recommendations is here reported. A multidisciplinary approach was used to establish the Working Group by involving radiologists, interventional radiologists, neuroradiologists, interventional cardiologists, occupational health specialists, medical physicists, radiation protection experts, radiographers and nurses. The Group operated as a “Consensus Conference”. Three main topics have been addressed: patient radiation protection (summarized in ten “golden rules”); staff radiation protection (summarized in ten “golden rules”); and education/training of interventional radiology professionals. In the “golden rules”, practical and operational recommendations were provided to help the professionals in optimizing dose delivered to patients and reducing their own exposure. Operative indications dealt also with continuing education and training, and recommendations on professional accreditation and certification. The “Consensus Conference” was the methodology adopted for the development of these recommendations. Involvement of all professionals is a winning approach to improve practical implementation of the recommendations, thus getting a real impact on the optimization of the interventional radiology practices.

The use of immune-enhancing enteral diets in the postoperative period has given contrasting results. The purpose of this prospective, randomized, double-blinded clinical study was to evaluate the effect of immunonutrition given perioperatively on cytokine release and nutritional parameters.Patients with cancer of the stomach or colo-rectum were eligible. Subjects consumed 1 L/d of either a control enteral formula (n = 25; control group) or a formula supplemented with arginine, omega-3 fatty acids, and RNA (n = 25; verum group) for 1 week before surgery. Both formulas were given by mouth. Six hours after the operation, jejunal infusion with the same diets was started and maintained for 7 days. Blood was drawn at different time points to assess albumin, prealbumin (PA), transferrin, cholinesterase activity, retinol binding protein (RBP), interleukin-2 receptors alpha (IL-2Ralpha), IL-6, and IL-1 soluble receptors (IL-1RII). The composite score of delayed hypersensitivity response (DHR) to skin test also was determined (the higher the score, the lower the immune response).During the 7 days of presurgical feeding, none of the above parameters changed in either group. Eight days after operation, in the control group, the concentration of PA and RBP was lower than in the verum group (0.18 vs 0.26 g/L for PA and 30.5 vs 38.7 mg/L for RBP; p.05). IL-2Ralpha concentration was 507 pg/mL in the verum group vs 238 pg/mL in the control group (p.001), whereas IL-6 and IL-1RII were higher in the control group than in the verum group (104 vs 49 and 328 vs 183 pg/mL, respectively; p.01). The DHR score was 0.68 in the control group vs 0.42 in the verum group (p.05).Perioperative feeding with a supplemented enteral diet modulates cytokine production and enhances cell-mediated immunity and the synthesis of short half-life proteins.

Hepatic injury secondary to warm ischemia-reperfusion (I/R) injury and alterations in haemostatic parameters are often unavoidable events after major hepatic resection. The release of inflammatory mediator is believed to play a significant role in the genesis of these events. It has been suggested that preoperative steroid administration may reduce I/R injury and improve several aspects of the surgical stress response. The aim of this prospective randomized study was to investigate the clinical benefits on I/R injury and systemic responses of preoperatively administered corticosteroids. Seventy-six patients undergoing liver resection were randomized either to a steroid group or to a control group. Patients in the steroid group received preoperatively 500 mg of methylprednisolone. Serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin, coagulation parameters, and inflammatory mediators, interleukin 6 and tumor necrosis factor alpha were compared between the 2 groups. Length of stay, and type and number of complications were recorded as well. Postoperative serum levels of ALT, AST, total bilirubin, and inflammatory cytokines were significantly lower in the steroid than in the control group at postoperative days 1 and 2. Changes in hemostatic parameters were also significantly attenuated in the steroid group. In conclusion, the incidence of postoperative complications in the steroid group tended to be significantly lower than the control group. It is of clinical interest that preoperative steroids administration before major surgery may reduce I/R injury, maintain coagulant/anticoagulant homeostasis, and reduce postoperative complications by modulating the inflammatory response.

Background: Interleukin-2 (IL-2) has been investigated as an adjunct to antiretroviral therapy (ART) because of its well-demonstrated capacity of stably increasing the number of peripheral CD4+ T cell lymphocytes. However, IL-2-related adverse events (AEs), including fever, tachycardia, hypotension, and respiratory failure, are typically close- and schedule-dependent and can potentially limit the application of IL-2 therapy in an outpatient setting. Nitric oxide (NO) is a potent vasodilator potentially responsible for some of the AEs caused by IL-2. Purpose: In this study, we determined NO production in a cohort of HIV-1 infected individuals receiving ART either alone or together with IL-2. Method: NO production, detected as plasma nitrate/nitrite levels by the Griess reaction, was evaluated in 3 groups of 10 individuals each. In the first group, subcutaneous (sc) administration of 12-15 million international units per day (MIU/d) of IL-2 was administered for 5 days every 8 weeks for 6 cycles together with ART; in the second group, IL-2 (6 MIU/d) was given sc for 5 days every 4 weeks for 12 cycles together with ART; whereas the third group received ART alone. Results: At baseline, the plasma nitrate/nitrite levels in the 2 groups of patients who received high and low doses of the cytokine along with ART were 28.5 +/- 18.1 mumol/L and 34.2 +/- 29.0 mumol/L, respectively. These levels were comparable to those of patients treated with only ART (18.6 +/- 22.4 mumol/L) and to those of 20 healthy controls (19.9 +/- 5.9 mumol/L). No significant increase of plasma nitrate/nitrite levels was observed by administration of either ART or ARTAL-2. In addition, NO production was not associated significantly with different levels of tumor necrosis factor-alpha, IL-6, or soluble IL-2 receptor alpha chain in 9 individuals with WHO grade 2 and 3 AEs. Conclusion: Our results indicate that NO is unlikely to be responsible for most side effects of IL-2 therapy in HIV-1 infected individuals. Because both IL-2 and virus multiplication have been reported to independently stimulate NO production, concomitant ART may curtail NO production through inhibition of HIV-1 replication.

To evaluate the safety and efficacy of 3 regimens of intermittent subcutaneous (sc) interleukin (IL)--2 in a phase 2 study, 61 antiviral drug-experienced human immunodeficiency virus (HIV)--positive patients were randomly assigned to one of the following study arms: antiretroviral therapy (ART) plus IL-2 (12 million IU [MIU] by continuous intravenous infusion, followed by 7.5 MIU twice a day, sc, every 8 weeks); ART plus IL-2 (7.5 MIU twice a day, sc, every 8 weeks); ART plus IL-2 (3 MIU twice a day, sc, every 4 weeks); or ART alone. A significant increase of circulating CD4 cells was observed in IL-2--treated subjects, compared with those given ART alone. Low doses of IL-2 were better tolerated. Despite the incomplete suppression of viral replication, IL-2 with ART did not increase either plasma viremia or cell-associated HIV DNA levels. Low doses of intermittent sc IL-2 induced a stable increase of peripheral CD4 cells that was indistinguishable from those associated with higher, less well-tolerated doses of IL-2.

Alterations in hemostatic parameters are a common finding after major hepatic resection. There is growing evidence that inflammation has a significant role in inducing coagulation disarrangement that follows major surgery. To determine whether preoperative methylprednisolone administration has a protective effect against the development of coagulation disorders, we evaluated the effect of preoperative steroids administration on changes in hemostatic parameters and plasma levels of inflammatory cytokines in patients undergoing liver surgery. Seventy-three patients undergoing liver resection were randomized to a steroid group or to a control group. Patients in the steroid group received 500 mg of methylprednisolone preoperatively. Serum levels of coagulation parameters (prothrombin time, platelets, fibrinogen, plasma fibrin degradation products [D-dimer], antithrombin III) and inflammatory mediators (IL-6 and TNF-alpha) were measured before and immediately after the operation and on postoperative days 1, 2, and 5. Multivariate analysis was performed to identify factors related to the characteristics of the patients and surgery affecting coagulation parameters between the two groups. Decreases in antithrombin III, platelet count and fibrinogen levels, prolongation of prothrombin time, and increases in the plasma fibrin degradation products were significantly suppressed by the administration of methylprednisolone. Cytokines production was also significantly suppressed by the administration of methylprednisolone, and there was significant correlation between plasma levels of cytokines and coagulation alterations. These findings suggest that preoperative methylprednisolone administration inhibits the development of coagulation disarrangements in patients undergoing liver resection, possibly through suppressing the production of inflammatory cytokines.

Objective To verify whether antiphospholipid antibodies (aPL) recognize and opsonize apoptotic human cells. Methods Apoptosis was induced via CD95 crosslinking or ultraviolet irradiation. IgG and anti-β2-glycoprotein I (anti-β2-GPI) antibodies were purified from patient sera by affinity chromatography. The aPL that bound to apoptotic cells were assessed by flow cytometry, and the subdomains recognized were identified by confocal microscopy. Human macrophages were derived from monocytes, and their ability to phagocytose 3H-labeled apoptotic bodies, whether opsonized or not opsonized by aPL, was assessed. Tumor necrosis factor α (TNFα) secretion was evaluated by enzyme-linked immunosorbent assay. Results The aPL, but not control Ig or Ig from aPL-negative patients, bound to apoptotic cells, but not to viable cells. Nuclear antigens were not recognized. Opsonization of apoptotic cells by aPL substantially enhanced recognition and binding by scavenger macrophages, with massive TNFα secretion. Conclusion Antiphospholipid antibodies facilitate apoptotic cell clearance by macrophages and trigger TNFα release, possibly enhancing the immunogenicity of the autoantigens they contain.