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Acute limb ischemia (ALI) is a serious medical emergency leading to high rate of complications, being not only limb- but even life-threatening, often despite early successful revascularization.1 Improvements in surgical techniques and perioperative patient care may have reduced the incidence of major complications in ALI patients over the years, but the results of trials published recently seem to document a persistent high risk, with reported 30-day amputation rate of 5% to 12%, mortality risk at 10% to 38%, combined incidence of amputation and death of 25% to 37.5%, at 1- to 6-month follow-up.2–7 Concomitant underlying diseases, the metabolic derangement that seems as a result of the acute insult, and a possible reperfusion injury following revascularization may account for this severe prognosis.8 Only anticoagulation, fasciotomy (when indicated), and perioperative supportive treatment are established strategies in ALI patients.1,8,9 Possible benefit from cardiovascular active therapies has recently been suggested in patients undergoing peripheral revascularization or noncardiac major surgical intervention.10,11 Moreover, several categories of compounds, potentially acting on pathobiological mechanisms of ischemia-reperfusion syndrome, have been tested in experimental models, but none of them has as yet been proven effective in clinical studies in patients with ALI.12–18 Because of their pharmacologic profile, prostanoids represent a potentially interesting category as adjuvant treatment of ALI patients.19 Several ischemia-reperfusion studies described the use of prostaglandins for reduction of postischemic tissue injuries, and even recently both PGE1 and PGI2 appeared as potent inhibitors of reflow-paradox in a preclinical model of reperfusion injury.20 Iloprost is a widely studied synthetic analogue of prostacyclin, with a 10-fold higher half-life than the native compound, and indicated in the treatment of severe chronic limb ischemia.1,21–23 Results from pilot studies and case reports also described the positive effects of iloprost in the management of acute ischemia secondary to various causes, particularly after accidental intra-arterial administration of drugs or toxic agents.24–26 Several preclinical studies have assessed the effects of iloprost in experimental ischemia-reperfusion injury and documented the actions of the compound on different pathophysiologic mechanisms potentially relevant for damage following ALI.27–32 A diagram indicating where iloprost can interfere in the mechanisms, leading from ischemia and reperfusion, to the development of no-reflow and reflow-paradox, is reported in Figure 1. 33 FIGURE 1. Pathobiological mechanisms leading from ischemia-reperfusion, to “no-reflow”/“reflow-paradox.” Points where iloprost can act are indicated (from de Donato et al33). Some years ago, we performed a placebo-controlled, double-blind pilot study in 30 patients with ALI undergoing Fogarty's thromboembolectomy. Encouraging results were obtained with the use of intraoperative and postoperative iloprost (lower incidence of major clinical events, more evident metabolic improvement by means of transcutaneous tensiometry).34 In this paper, we report the results of ILoprost in Acute Ischemia of Lower Limbs (ILAILL) study, a larger, multicenter trial including patients undergoing all types of surgical revascularization, who received iloprost or placebo administration during intervention and therefore for 4 to 7 days, and were observed for a 3-month postoperative period.

Objectives To evaluate the effects of iloprost, in addition to surgery, on the outcome of acute lower limb ischemia (ALLI). Design Post-hoc analysis of a randomized, double-blind, placebo-controlled study. Methods In the context of the ILAILL (ILoprost in Acute Ischemia of Lower Limbs) study, 192 elderly patients (>70 years old) undergoing surgery for ALLI were assigned to receive perioperative iloprost (intra-arterial, intra-operative bolus of 3000ng, plus intravenous infusion of 0.5–2.0ng/kg/min for six hours/day for 4–7 days following surgery), or placebo (iloprost: n =100; placebo: n =92). Patients were followed-up for three-months following surgical revascularization. Results The combined incidence of death and amputation (primary study end-point) was significantly reduced in patients treated with iloprost (16.0% vs 27.2% in the placebo group; hazard ratio 1.99, 95% confidence interval 1.05–3.75, p =0.03). A statistically significant lower mortality (6.0%) was reported in patients receiving iloprost, compared to controls (15.2%) (hazard ratio 2.93, 1.11–7.71, p =0.03). The overall incidence of death and major cardiovascular events was lower in patients receiving iloprost compared to those assigned placebo (24.0% and 35.9%, respectively), at the limits of statistical significance (relative risk 1.64, 0.97–2.79, p =0.06). Conclusions These results confirm the poor outcome in elderly patients with ALLI. Based on a subgroup analysis iloprost, as an adjuvant to surgery, appears to reduce the combined end-point of death and amputation.

Lavori di una commissione nominata dal Rettore dell'Università di Napoli Federico II per definire in termini scientifici la pericolosità dell'area vesuviana in relazione alla ripresa dell'attività del Vesuvio e per delineara una strategia globale di intervento.

Studies into the use of fissile elements and uranium for the production of atomic weapons in particular and of energy in general were initially kept a strict secret when research was begun during the second world war. Even after the war, until 1952, the U.S.A., which possessed almost all the scientific and technological information on the refining and uses of uranium, kept its knowledge even from its most loyal allies. The MacMahon Act forbade the U.S.A. from giving any help, which included the transfer of information and technology, to any other country.