Bench-to-bedside review: preventive measures for contrast-induced nephropathy in critically ill patients

An increasing number of diagnostic imaging procedures requires the use of intravenous radiographic contrast agents, which has led to a parallel increase in the incidence of contrast-induced nephropathy. Risk factors for development of contrast-induced nephropathy include pre-existing renal dysfunction (especially diabetic nephropathy and multiple myeloma-associated nephropathy), dehydration, congestive heart failure and use of concurrent nephrotoxic medication (including aminoglycosides and amphotericin B). Because contrast-induced nephropathy accounts for a significant increase in hospital-acquired renal failure, several strategies to prevent contrast-induced nephropathy are currently advocated, including use of alternative imaging techniques (for which contrast media are not needed), use of (the lowest possible amount of) iso-osmolar or low-osmolar contrast agents (instead of high-osmolar contrast agents), hyperhydration and forced diuresis. Administration of N-acetylcysteine, theophylline, or fenoldopam, sodium bicarbonate infusion, and periprocedural haemofiltration/haemodialysis have been investigated as preventive measures in recent years. This review addresses the literature on these newer strategies. Since only one (nonrandomized) study has been performed in intensive care unit patients, at present it is difficult to draw firm conclusions about preventive measures for contrast-induced nephropathy in the critically ill. Further studies are needed to determine the true role of these preventive measures in this group of patients who are at risk for contrast-induced nephropathy. Based on the available evidence, we advise administration of N-acetylcysteine, preferentially orally, or theophylline intravenously, next to hydration with bicarbonate solutions

Interventional cardiology : Cost-effectiveness of PCI guided by fractional flow reserve

Coronary revascularization strategies have been evaluated in numerous clinical trials. As coronary revascularization has become more common, concerns over financial costs have increased

Utilizing Risk Scores in Determining the Optimal Revascularization Strategy for Complex Coronary Artery Disease

Percutaneous coronary intervention (PCI) of multivessel and/or left main stem disease have been shown to be potentially legitimate revascularization alternatives in appropriately selected patients. Risk stratification is an important component in guiding patients to identify the most appropriate revascularization modality (PCI or coronary artery bypass grafting [CABG]) in conjunction with the Heart Team. The aim of this paper is to give the clinician a concise overview of the important established and evolving contemporary risk models in aiding this decision-making process. Risk models, based on clinical and anatomical variables alone, the novel concept of functional anatomical risk scores, and risk models combining aspects from both clinical and anatomical scores, are all discussed. The emerging concepts of the patient-empowered risk/benefit tradeoff between PCI and CABG to help personalize the choice of revascularization modality are also explored

A modified cementing technique using BoneSource to augment fixation of the acetabulum in a sheep model

Background and purpose Our aim was to prove in an animal model that the use of HA paste at the cement-bone interface in the acetabulum would improve fixation. We examined, in sheep, the effect of interposing a layer of hydroxyapatite cement around the periphery of a polyethylene socket prior to fixing it using polymethylemethacrylate (PMMA). Methods We made a randomized study involving 22 sheep to test whether the application of BoneSource hydroxyapatite material to the surface of the ovine acetabulum prior to cementing a polyethylene cup at hip arthroplasty improved the fixation and the nature of the interface. We studied the gross radiographical appearance of the implant-bone interface and the histological appearance at the interface. Results There were more radiolucencies evident in the control group. Histologically, only sheep randomized into the BoneSource group exhibited a fully osseointegrated interface. Use of the hydroxyapatite material did not confer any detrimental effects. In some cases the material appeared to have been fully resorbed. When the material was evident on histological section, it was incorporated into an osseointegrated interface. There was no giant cell reaction present in any case. There was no evidence of migration of BoneSource to the articulation. Interpretation The application of HA material prior to cementation of a socket produced an improved interface. The technique may be useful in man with to extend the longevity of the cemented implant by protecting the socket interface from the effect of hydrodynamic fluid flow and particulate debris

Monitoring the final orbital decay and the re-entry of Tiangong-1 with the Italian SST ground sensor network

The uncontrolled re-entry of spacecraft and upper stages is quite common, occurring nearly every week. Among them, intact objects having a mass greater than five metric tons re-enter, on average, 1–2 times per year. Therefore, the re-entry of the first Chinese Space Station, Tiangong-1, was far from unusual, but attracted anyway a great worldwide attention and some concerns. For these reasons, the Italian component of the European SST (Space Surveillance and Tracking) consortium took this opportunity for carrying out a national exercise. According to Chinese official sources, the ground control of Tiangong-1 was lost in March 2016, precluding the planned de-orbiting in the South Pacific Ocean Unpopulated Area (SPOUA). Tiangong-1 consisted of a cylindrical section, 10:5 m in length and 3:4 m in (maximum) diameter, with two rectangular solar panels of 3 m × 7 m. The mass was estimated to be around 7500 kg. The Italian network of sensors activated for the campaign included mono-static and bi-static radars, optical telescopes, a laser ranging station and a network of all-sky cameras, originally deployed for the observation of fireballs and bolides. In addition to providing complementary information, concerning the orbit, the attitude and the photometry of Tiangong-1, this quite heterogeneous collection of national assets provided also the occasion for testing, in an operational environment, the Italian sensor tasking preparedness and the data acquisition, exchange and processing capabilities within the European SST consortium. In this respect, it is important to remember that in 2014 the European Commission, well aware of the topic criticality, took the commitment to implement a European network of sensors for surveillance and tracking of objects in Earth's orbit by starting a dedicated SST support framework program. Italy, France, Germany, Spain and UK joined it and constituted, together with SatCent, the front desk for SST services, the EUSST Consortium. In this paper, a description of the Tiangong-1 monitoring activities and of the main observations results obtained by the Italian sensor network are reported. Attention is also devoted to the coordination aspects of several Italian entities (military, civil and research organizations) that worked together. Finally, a description of the re-entry prediction and alert procedure for the national civil protection authorities is presented

NOXA as critical mediator for drug combinations in polychemotherapy

During polychemotherapy, cytotoxic drugs are given in combinations to enhance their anti-tumor effectiveness. For most drug combinations, underlying signaling mechanisms responsible for positive drug–drug interactions remain elusive. Here, we prove a decisive role for the Bcl-2 family member NOXA to mediate cell death by certain drug combinations, even if drugs were combined which acted independently from NOXA, when given alone. In proof-of-principle studies, betulinic acid, doxorubicin and vincristine induced cell death in a p53- and NOXA-independent pathway involving mitochondrial pore formation, release of cytochrome c and caspase activation. In contrast, when betulinic acid was combined with either doxorubicine or vincristine, cell death signaling changed considerably; the drug combinations clearly depended on both p53 and NOXA. Similarly and of high clinical relevance, in patient-derived childhood acute leukemia samples the drug combinations, but not the single drugs depended on p53 and NOXA, as shown by RNA interference studies in patient-derived cells. Our data emphasize that NOXA represents an important target molecule for combinations of drugs that alone do not target NOXA. NOXA might have a special role in regulating apoptosis sensitivity in the complex interplay of polychemotherapy. Deciphering the differences in signaling of single drugs and drug combinations might enable designing highly effective novel polychemotherapy regimens

Prognostic value of fractional flow reserve: Linking physiologic severity to clinical outcomes

BACKGROUND: Fractional flow reserve (FFR) has become an established tool for guiding treatment, but its graded relationship to clinical outcomes as modulated by medical therapy versus revascularization remains unclear.OBJECTIVES: The study hypothesized that FFR displays a continuous relationship between its numeric value and prognosis, such that lower FFR values confer a higher risk and therefore receive larger absolute benefits from revascularization.METHODS: Meta-analysis of study- and patient-level data investigated prognosis after FFR measurement. An interaction term between FFR and revascularization status allowed for an outcomes-based threshold.RESULTS: A total of 9,173 (study-level) and 6,961 (patient-level) lesions were included with a median follow-up of 16 and 14 months, respectively. Clinical events increased as FFR decreased, and revascularization showed larger net benefit for lower baseline FFR values. Outcomes-derived FFR thresholds generally occurred around the range 0.75 to 0.80, although limited due to confounding by indication. FFR measured immediately after stenting also showed an inverse relationship with prognosis (hazard ratio: 0.86, 95% confidence interval: 0.80 to 0.93; p < 0.001). An FFR-assisted strategy led to revascularization roughly half as often as an anatomy-based strategy, but with 20% fewer adverse events and 10% better angina relief.CONCLUSIONS: FFR demonstrates a continuous and independent relationship with subsequent outcomes, modulated by medical therapy versus revascularization. Lesions with lower FFR values receive larger absolute benefits from revascularization. Measurement of FFR immediately after stenting also shows an inverse gradient of risk, likely from residual diffuse disease. An FFR-guided revascularization strategy significantly reduces events and increases freedom from angina with fewer procedures than an anatomy-based strategy