[Acute renal failure following cardiac surgery]. / Insufficienza renale acuta post-cardiochirurgica.

Acute renal failure (ARF) develops in 1-30% of patients who undergo cardiac surgery and is associated with a high mortality rate (15-30%). Several risk factors (pre- and intra-operative) for ARF have been identified. Pre-operative factors are strictly related to cardiovascular disease, advanced age and baseline renal dysfunction, while intra-operative factors are linked with the type of cardiac surgery, the duration of cardiopulmonary bypass and aortic cross-clamping. These factors provide an opportunity to quantify the risk of ARF based on pre-operative data, and for this purpose a clinical score to predict post-operative ARF has recently been developed. Moreover, this score could allow the identification of those patients who may take advantage of preventive strategies. Mortality in patients who develop severe ARF requiring dialysis is particularly high (50-80%). Therefore, an early diagnosis of ARF and a timely and aggressive renal replacement therapy could improve the outcome.

[Pharmacokinetic principles and drug-dosing adjustments during continuous renal replacement therapies (CRRT)]. / Principi di farmacocinetica e aggiustamento posologico dei farmaci nell terapie sostitutive renali continue (CRRT).

In the critically ill, acute renal failure (ARF) and "Multiple Organ Dysfunction Syndrome" (MODS) can be associated with significant modifications of many pharmacokinetic parameters, such as protein binding, volume of distribution and total body clearance. The start of renal replacement therapy (RRT) represents an additional variable to take in consideration for drug-dosing adjustments. Drugs significantly eliminated by the kidney are likely to be removed during RRT and a supplemental dose or further dosing adjustments are required if extracorporeal clearance is more than 25-30% of total body clearance. The impact of RRT on plasma drug concentrations can be substantially different in relation to the type of treatment (diffusive, convective or both), membrane characteristics (low-flux or high-flux), filter surface area and prescribed dialysis dose. The molecular weight cut-offs of high-flux membrane are much higher than the molecular weight of most drugs. Therefore, molecular size will not be a limitation for the removal of the unbound fraction of the drugs most commonly used in the critically ill undergoing continuous renal replacement therapy (CRRT). However, diffusive clearance could be significantly lower than convective clearance for drugs in the middle molecular weight range. In any case, the extracorporeal clearances report-ed with the use of high-volume CRRT (>50-60 L/2 h) are often surprisingly elevated and can lead to drug underdosing in clinical conditions where adequate antibiotic treatment is essential.

Preliminary design of a Gd-NCT neutron beam based on compact D-T neutron source.

Gadolinium has been recently proposed, as neutron capture agent in NCT (Neutron Capture Therapy), due to both the nuclide high neutron capture cross section, and the remarkable selective uptake inside tumour tissue that Gd-loaded compounds, can provide. When a neutron external source is supplied, different Gd nuclear reactions, and the generated Auger electrons in particular, cause a high local energy deposition, which results in a tumour cell inactivation. Preliminary micro- as well as macrodosimetric Monte Carlo computational investigations show that the tumour-to-healthy tissue biological damage ratio is in close relation to the neutron beam energy spectrum. The results points out that the optimum neutron spectrum, to be used for Gd-NCT, seems to lie in the 1 to 10 keV energy range. In order to 'tailor' such spectra, an original, accelerator-driven, neutron source and spectrum shaping assembly for hospital-based Gd-NCT are presented and preliminary results are reported.

Experimental and computational validation of BDTPS using a heterogeneous boron phantom.

The idea to couple the treatment planning system (TPS) to the information on the real boron distribution in the patient acquired by positron emission tomography (PET) is the main added value of the new methodology set-up at DIMNP (Dipartimento di Ingegneria Meccanica, Nucleare e della Produzione) of University of Pisa, in collaboration with the JRC (Joint Research Centre) at Petten (NL). This methodology has been implemented in a new TPS, called Boron Distribution Treatment Planning System (BDTPS), which takes into account the actual boron distribution in the patient's organ, as opposed to other TPSs used in BNCT that assume an ideal uniform boron distribution. BDTPS is based on the Monte Carlo technique and has been experimentally validated comparing the computed main parameters (thermal neutron flux, boron dose, etc.) to those measured during the irradiation of an ad hoc designed phantom (HEterogeneous BOron phantoM, HEBOM). The results are also in good agreement with those obtained by the standard TPS SERA and by reference calculations carried out using an analytical model with the MCNP code. In this paper, the methodology followed for both the experimental and the computational validation of BDTPS is described.