An innovative iterative thresholding algorithm for tumour segmentation and volumetric quantification on SPECT images: Monte Carlo-based methodology and validation.

PURPOSE: Positron emission tomography (PET) and single-photon emission computed tomography (SPECT) imaging play an important role in the segmentation of functioning parts of organs or tumours, but an accurate and reproducible delineation is still a challenging task. In this work, an innovative iterative thresholding method for tumour segmentation has been proposed and implemented for a SPECT system. This method, which is based on experimental threshold-volume calibrations, implements also the recovery coefficients (RC) of the imaging system, so it has been called recovering iterative thresholding method (RIThM). The possibility to employ Monte Carlo (MC) simulations for system calibration was also investigated. METHODS: The RIThM is an iterative algorithm coded using MATLAB: after an initial rough estimate of the volume of interest, the following calculations are repeated: (i) the corresponding source-to-background ratio (SBR) is measured and corrected by means of the RC curve; (ii) the threshold corresponding to the amended SBR value and the volume estimate is then found using threshold-volume data; (iii) new volume estimate is obtained by image thresholding. The process goes on until convergence. The RIThM was implemented for an Infinia Hawkeye 4 (GE Healthcare) SPECT/CT system, using a Jaszczak phantom and several test objects. Two MC codes were tested to simulate the calibration images: SIMIND and SimSet. For validation, test images consisting of hot spheres and some anatomical structures of the Zubal head phantom were simulated with SIMIND code. Additional test objects (flasks and vials) were also imaged experimentally. Finally, the RIThM was applied to evaluate three cases of brain metastases and two cases of high grade gliomas. RESULTS: Comparing experimental thresholds and those obtained by MC simulations, a maximum difference of about 4% was found, within the errors (+/- 2% and +/- 5%, for volumes > or = 5 ml or < 5 ml, respectively). Also for the RC data, the comparison showed differences (up to 8%) within the assigned error (+/- 6%). ANOVA test demonstrated that the calibration results (in terms of thresholds or RCs at various volumes) obtained by MC simulations were indistinguishable from those obtained experimentally. The accuracy in volume determination for the simulated hot spheres was between -9% and 15% in the range 4-270 ml, whereas for volumes less than 4 ml (in the range 1-3 ml) the difference increased abruptly reaching values greater than 100%. For the Zubal head phantom, errors ranged between 9% and 18%. For the experimental test images, the accuracy level was within +/- 10%, for volumes in the range 20-110 ml. The preliminary test of application on patients evidenced the suitability of the method in a clinical setting. CONCLUSIONS: The MC-guided delineation of tumor volume may reduce the acquisition time required for the experimental calibration. Analysis of images of several simulated and experimental test objects, Zubal head phantom and clinical cases demonstrated the robustness, suitability, accuracy, and speed of the proposed method. Nevertheless, studies concerning tumors of irregular shape and/or nonuniform distribution of the background activity are still in progress.

[Against CRRT: hybrid treatments are gaining ground]. / Contro la CRRT: le terapie ibride diventeranno la tecnica dominante nei prossimi anni.

Renal replacement therapies (RRT) are a key component of the therapeutic approach to acute kidney injury in the ICU. They are usually performed as intermittent hemodialysis (IHD) or continuous RRT (CRRT). Each of these therapies has its advantages and disadvantages. The so-called ''hybrid'' therapies have been gaining popularity in recent years. This kind of treatment, known as ''sustained low-efficiency dialysis'' or SLED, has most of the advantages of IHD and CRRT, without sharing their disadvantages and limitations.

[Management of central venous catheter: prevention of thrombosis and bacteremia]. / Gestione del catetere venoso centrale: prevenzione della trombosi e della batteriemia.

The use of central venous catheters (CVC) as vascular access has increased considerably in recent years, especially because of the progressive aging and increasingly severe comorbidities of the dialysis population. The main factors limiting the long-term use of a hemodialysis catheter are thrombosis and infection. Thrombosis can be treated with thrombolytic agents and prevented effectively by means of anticoagulants. CVC infections represent the main cause of morbidity and mortality in these patients. This is the reason why systemic antibiotic therapy must be started very rapidly, based even on a simple clinical suspicion and in the absence of any confirmation of bacteremia. If antibiotic therapy fails, the CVC must be removed. The recent introduction of antibiotic lock therapy appears to be an effective means to prevent bacteremia. However, it must not be forgotten that the best way of preventing CVC-related bacteremia is by reinforcing all control procedures, with the active involvement of patients and staff.

[Is intermittent peritoneal dialysis with icodextrin a valid option in the long-term treatment of refractory congestive heart failure?]. / La dialisi peritoneale intermittente con i icodestrina e' una valida opzione nel trattamento a lungo termine dello scompenso cardiaco congestizio refrattario?

Refractory congestive heart failure (CHF) is affected by a very high morbidity and mortality. We report our experience in the long-term treatment of refractory CHF (NYHA class IV) by means of intermittent peritoneal dialysis (PD) with icodextrin (ICO) solutions in 4 male patients with a mean age of 71.5 + or - 5.6 (standard deviation) years and with a variable degree of chronic renal failure: 1 nocturnal exchange with ICO in 3 patients and 2 exchanges (ICO + isotonic dextrose solution) in 1 patient. The mean PD follow-up period was 24.3 + 15.6 months. After stabilization on PD, all patients had a statistically significant increase in daily diuresis (from 587.5 + or - 165.2 to 1700.0 + or - 141.4 mL, p < 0.003), a statistically significant decrease in body weight (11.3 + or - 3.4 kg, p < 0.007), and a statistically significant improvement in NYHA class (from 4.0 + or - 0.0 to 2.5 + or - 2.6, p < 0.01). Three patients had no hospitalizations due to cardiac illness in the PD follow-up period. No episodes of peritonitis occurred. Three patients died after 11, 13 and 43 months of PD treatment: 2 because of sudden death and 1 because of neoplastic cachexia. No death could be attributed to any complication related to PD treatment. Intermittent PD with ICO solutions can be proposed as a long-term treatment modality for refractory CHF. It allows an improvement in quality - if not quantity - of life. Randomized controlled trials are needed to confirm the evidence derived from case reports.

[We should strive for optimal hemodialysis: treatment time is the key factor]. / Dovremmo lottare strenuamente per una emodialisi ottimale: il tempo di trattamento e' il suo fattore chiave.

Nephrologists should strive for optimal hemodialysis. Convection, at least as it is conceived today, is far from optimal and the same is true of standard bicarbonate dialysis. A very recent paper by Eloot et al (Kidney Int 2008: 73: 765-70) clearly illustrates the way towards optimal hemodialysis by showing in a simple and intelligent manner the independent effect of the factor time on the adequacy of hemodialysis. Furthermore, it simplifies the conceptual scenario of dialysis adequacy and points to diffusion mechanisms as the key modality to remove uremic retention solutes. Thus, it is clear that we should strive for longer and/or more frequent dialysis sessions. Long nocturnal home hemodialysis every other night appears to be more appealing to patients than 5 to 7 dialysis sessions a week. The Italian Society of Nephrology should promote trials and the National Health Service should provide funds for these promising hemodialysis schedules.

[Occlusion of hemodialysis vascular accesses by means of endovascular procedures]. / Chiusura degli accessi vascolari per emodialisi con procedure endovascolari.

Correct management of complications is crucial to the long-term survival of vascular access for hemodialysis. The present work report our experience with endovascular procedures in the occlusion of complicated arteriovenous fistulas (AVFs) and grafts in patients with a high surgical risk. Among the endovascular procedures carried out between January 2003 and December 2006, all those regarding the occlusion of vascular accesses by means of embolization or exclusion were selected retrospectively. Embolization means the release into the circulation of material to occlude the vascular lumen; exclusion is obtained by means of covered stents, which, when placed in a blood vessel, exclude its ramifications. Seven procedures of endovascular occlusion of vascular accesses were performed in the study period. All patients were considered as having a high surgical risk or presented technical difficulties related to surgical intervention. Venous hypertension was the indication in 5 cases and grade III or IV steal syndrome was the indication in 2 cases. Six AVFs were treated: 2 distal radiocephalic, 1 brachiocephalic, 2 brachiobasilic, and 1 Gracz AVF; an antebrachial graft was also treated. Occlusion was obtained in 4 cases by means of embolization and in 3 cases by means of exclusion. The technical success was 100% with virtually no complications. Endovascular occlusion of vascular access represents an effective and safe procedure in selected cases, also when compared with the surgical approach. Furthermore, the different technical solutions available allow to adequately solve the problems linked to anatomical variability and to the sites of the vascular accesses.

[A particular case of hemodialysis with a single-pass batch system]. / Un caso particolare di emodialisi con un single pass batch system.

The GENIUS 90 Therapy System (GENIUS) (Fresenius Medical Care, Bad Homburg, Germany) is a mobile dialysis machine with a 90-liter, thermally insulated glass tank. Fresh dialysis fluid is prepared by mixing sterile ingredients (electrolytes and glucose) with preheated ultrapure water. Here we report the case of a 60-year-old hemodialysis patient who was hospitalized in our unit in November 2005 because of an ischemic stroke affecting the left temporal-parietal-occipital region of the brain. The persisting clinical features included right hemiplegia, motor aphasia, epilepsy and stage I coma. The patient started thrice-weekly GENIUS hemodialysis treatment (about 270 sessions to date) in his hospital room with no continuous nursing assistance. In conclusion, GENIUS is able to offer user-friendly, high-quality and adequate dialysis treatment.

[Management of arteriovenous fistula: anastomosis and more....]. / Gestione della fistola arterovenosa: l'anastomosi e oltre...

The huge amount of human and economic resources necessary for a vascular access creation in haemodialysis strongly requires a very careful patient assessment and the choice of the most appropriate procedures, both aiming at improving quality of care and optimizing available resources. This review focuses on arteriovenous fistula (AVF) monitoring and surveillance, not only by following current guidelines, but also by exploring the most interesting data of the literature; attention is particularly focused on the haemodynamic aspects of AVF, which play a relevant role not only in himself. the natural history of vascular access, but also of the patient.

[Intradialytic hypotension: The role of volemia]. / L'ipotensione intradialitica: ruolo della volemia.

Intradialytic hypotension (IDH) is one of the most serious complications in renal replacement therapy (RRT). The main cause of IDH is hypovolemia due to an imbalance between the amount of fluid removed and the refilling capacity of the intravascular compartment. IDH occurs when compensatory mechanisms for hypovolemia are overwhelmed by excessive fluid removal. As long as RRT is limited to only a few hours per week, IDH will continue to be a relevant problem. Research has focused mainly on enlarging the compensatory capacity for ultrafiltration-induced hypovolemia. This review critically discusses the technical approaches that have been recently introduced to the therapy with the promise of reducing hypovolemia-induced IDH.

[Cardiac arrhythmias in patients with renal insufficiency treated with periodic hemodialysis]. / Le aritmie cardiache nel paziente con insufficienza renale ed in trattamento emodialitico periodico.

Despite substantial progress in dialysis technology, cardiovascular disease remain the sole major cause of death in chronic dialysis patients. Nearly half of deaths on chronic maintenance hemodialysis are secondary to myocardial infarction, cardiac arrest, malignant arrhythmias and other cardiac causes. In fact, diabetes, anemia, hyperparathyroidism, and hypertension wide prevalence among chronic dialysis patients foster structural heart diseases. Moreover fluid overload and metabolic abnormalities such as metabolic acidosis, dyskalemia, dysmagnesemia lead to an increased risk of clinically significant ventricular arrhythmias and sudden cardiac death. During dialysis patients show a non-homogeneous repolarization through an increase in Q-T duration and Q-T dispersion. The dialysis-related sudden variation in extra-cellular potassium, calcium and pH levels may be contributing factors to the genesis of an electrical disequilibrium in myocardial cells. One of the potential therapeutic options is, in fact, adjusting the dialysis bath. The K profiling with non-constant K concentration in the dialysate, but with high concentration in the first hour of dialysis and progressive reduction until the end of the session, seems very promising in reducing the arrhythmic risk in cardiomyopathy patients.

An Adaptive Thresholding Method for BTV Estimation Incorporating PET Reconstruction Parameters: A Multicenter Study of the Robustness and the Reliability.

OBJECTIVE: The aim of this work was to assess robustness and reliability of an adaptive thresholding algorithm for the biological target volume estimation incorporating reconstruction parameters. METHOD: In a multicenter study, a phantom with spheres of different diameters (6.5-57.4 mm) was filled with (18)F-FDG at different target-to-background ratios (TBR: 2.5-70) and scanned for different acquisition periods (2-5 min). Image reconstruction algorithms were used varying number of iterations and postreconstruction transaxial smoothing. Optimal thresholds (TS) for volume estimation were determined as percentage of the maximum intensity in the cross section area of the spheres. Multiple regression techniques were used to identify relevant predictors of TS. RESULTS: The goodness of the model fit was high (R(2): 0.74-0.92). TBR was the most significant predictor of TS. For all scanners, except the Gemini scanners, FWHM was an independent predictor of TS. Significant differences were observed between scanners of different models, but not between different scanners of the same model. The shrinkage on cross validation was small and indicative of excellent reliability of model estimation. CONCLUSIONS: Incorporation of postreconstruction filtering FWHM in an adaptive thresholding algorithm for the BTV estimation allows obtaining a robust and reliable method to be applied to a variety of different scanners, without scanner-specific individual calibration.

Randomized, single blind, controlled trial of inhaled glutathione vs placebo in patients with cystic fibrosis.

BACKGROUND: In cystic fibrosis (CF) the defective CF transmembrane conductance regulator protein may be responsible for the impaired transport of glutathione (GSH), the first line defense of the lung against oxidative stress. The aim of this single-blind, randomized, placebo-controlled trial was to evaluate the effect of inhaled GSH in patients with CF. METHODS: 54 adult and 51 pediatric patients were randomized to receive inhaled GSH or placebo twice daily for 12 months. RESULTS: Twelve month treatment with inhaled GSH did not achieve our predetermined primary outcome measure of 15% improvement in FEV1%. Only in patients with moderate lung disease, 3, 6 and 9 months therapy with GSH resulted in a statistically significant increase of FEV1 values from the baseline. Moreover GSH therapy improved 6-minute walking test in pediatric population. GSH was well tolerated by all patients. CONCLUSIONS: Inhaled GSH has slight positive effects in CF patients with moderate lung disease warranting further study. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT01450267; URL: www.clinicaltrialsgov.

Optimization of the convection volume in online post-dilution haemodiafiltration: practical and technical issues.

In post-dilution online haemodiafiltration (ol-HDF), a relationship has been demonstrated between the magnitude of the convection volume and survival. However, to achieve high convection volumes (>22 L per session) detailed notion of its determining factors is highly desirable. This manuscript summarizes practical problems and pitfalls that were encountered during the quest for high convection volumes. Specifically, it addresses issues such as type of vascular access, needles, blood flow rate, recirculation, filtration fraction, anticoagulation and dialysers. Finally, five of the main HDF systems in Europe are briefly described as far as HDF prescription and optimization of the convection volume is concerned.

Successful parathyroid gland autotransplantation in the rat using a simplified cryopreservation technique.

In the present work a simplified technique for cryopreservation of parathyroid glands was compared to the generally used technique needing a programmed freezer. Four groups of rats had total parathyroidectomy. In two of them the glands were cryopreserved and reimplanted 10 days after ablation. The other two groups had, respectively, immediate parathyroid autotransplantation and no autotransplantation. During a follow-up of 60 days, plasma calcium remained low and plasma phosphorus elevated in all aparathyroid rats of the last group. In the group of rats with immediate parathyroid reimplantation, both mean plasma calcium and phosphorus values rapidly returned to the normal values observed before operation. In the rats that had the simplified parathyroid cryopreservation technique, mean plasma phosphorus also returned to the normal range and mean plasma calcium to nearly normal. However, in the group of rats with the classical cryopreservation method, the mean plasma calcium and phosphorus levels remained far from normal in the majority of animals. It was concluded that parathyroid glands of the rat could be successfully autografted after previous freezing using a simplified cryopreservation technique. The results obtained were comparable with, even though not as perfect as, that observed after immediate autotransplantation. If suitable for human parathyroid gland fragments, this technique would allow a more general application of parathyroid tissue cryopreservation.

Complement potentiates the degradation of myelin proteins by plasmin: implications for a mechanism of inflammatory demyelination.

A previous finding, that the basic protein in lyophilized bovine myelin was degraded by macrophage-conditioned media in the presence of plasminogen, suggested that the macrophage-secreted plasminogen activator, along with plasminogen, might have a role in destruction of myelin during inflammatory demyelination. To approximate more closely the conditions expected in vivo, plasmin, or macrophage supernatants plus plasminogen, were incubated with freshly homogenized bovine white matter or freshly isolated myelin, as distinguished from lyophilized myelin. Under these conditions basic protein was not degraded. Phospholipase or lysolecithin potentiated the degradation of basic protein in fresh bovine myelin by plasmin; however, the cultured macrophages did not secrete significant amounts of phospholipase and plasminogen activator simultaneously into the culture media after activation with any of several different agents. Recently myelin was shown to activate complement. After preincubation of fresh myelin with guinea pig serum, as a source of complement, the basic and proteolipid proteins were vulnerable to plasmin or to macrophage-conditioned media plus plasminogen. C3-depleted and C4-deficient sera were not effective, suggesting that these complement components were required for the serum effect. Hypothetically, then, degradation of myelin proteins in the CNS could be initiated by plasminogen activator, secreted by infiltrating macrophages, plus complement and plasminogen, which could enter the CNS through lesions in the blood-brain barrier.

Renal abnormalities in Mayer-Rokitanski-Küster-Hauser syndrome.

Mayer-Rokitanski-Kuster-Hauser (MRKH) syndrome, is a rare disorder characterized by the congenital absence of the uterus and vagina. The prevalence has been reported as one in 4000-5000 female births. Patients with MRKH syndrome have a 46.XX karyotype and normal secondary sex characteristics. The external genitalia appear normal, but only a shallow vaginal pouch is present. Ovarian function is normal. A 54-year-old woman came to our observation for the treatment of arterial hypertension. Her history involved primary amenorrhea and sterility. She had undergone abdominal and pelvic sonography as a routine screening and they had shown the absence of the uterus, left renal agenesis and a contralateral pelvic kidney. These findings were confirmed by urography and CT scan of the abdomen. Gynecologic examination showed a small vaginal pouch (2 cm). Thus, the diagnosis of MRKH syndrome with associated congenital anomalies of the upper urinary tract was made for the first time in this lady at the age of 54 years. Associated congenital anomalies of the upper urinary tract are reported to occur in 30-40% of all cases of MRKH syndrome. No specific figures are available on what percentage of women with missing kidney might also have MRKH syndrome. However, in 40-50% of patients with renal agenesis, an associated genital anomaly has been found. In conclusion, this report is intended to remind our community of the existence of congenital renal abnormalities associated with gynecologic abnormalities, a field of nephrology usually amply neglected.

Anterior ischemic optic neuropathy and dialysis: role of hypotension and anemia.

The pathogenesis of anterior ischemic optic neuropathy (AION) primarily involves interference with the posterior ciliary artery blood supply to the prelaminar optic nerve. Uremic patients often have coexisting pathology such as hypotension (decreased blood delivery), or hypertension, atherosclerosis (increased resistance to blood supply), and anemia (low blood oxygen carrying capacity), predisposing them to AION. We describe a 49-year-old patient on dialysis for many years. He had long-standing hypotension, worsened during each dialysis treatment. He awoke one morning at age 48 complaining of blurred vision in the left inferior field. Based on the clinical course, funduscopic and fluorangiographic examination and visual field defects, AION was diagnosed. Nine months after the loss of vision in the left eye, vision in the right eye became blurred and worsened over the next 24 hours. The diagnosis of AION in the right eye was made. At the last examination ten months later, the patient, still amaurotic, was given a very poor prognosis for further recovery of the visual defects. Surprisingly, very few cases of AION have been reported in chronic uremic patients on dialysis: to the best of our knowledge, only 12 including ours. Most of these cases share some features, including hypotension above all and anemia as common risk factors. Neither the type of dialysis treatment (hemo-, peritoneal dialysis) nor sex seem to have any influence on the occurrence of AION. Uremic children can be affected. What is striking in the three published pediatric cases is that they all had polycystic kidney disease. Treatment of AION in all 12 cases consisted of a combination of steroids, i.v. saline, blood transfusions and rhEpo. AION was more frequently bilateral and irreversible, ending in permanent amaurosis. In conclusion, this study aims to stress that most cases of AION occurring in chronic uremic patients on dialysis have some common features, including hypotension above all and anemia as common risk factors.

Pharmacokinetics of netilmicin in hypertonic hemodiafiltration and standard hemodialysis.

Recently, we developed a peculiar model of hemodiafiltration (HDF), in which a conventional acetate hemodialysis (HD) is combined with a high flux dialyzer, a high ultrafiltration flow rate and a postdilution hypertonic reinfusion (H HDF). The pharmacokinetics of netilmicin (N), a relatively new aminoglycoside, were evaluated during 5 sessions of H HDF of 180 min and 2 sessions of HD of 270 min in the same 8 patients with a comparable blood (approximately 400 ml/min) and dialysate flow rate (approximately 520 ml/min). Additional studies were performed in 7 out of the 8 patients after 2 sessions of H HDF and one session of HD. N clearance, calculated both as plasma water and total body clearance, was so exceedingly higher during H HDF than during HD, that the amount of drug removed by H HDF in 180 min was still significantly higher than that removed by HD in 270 min. Consequently, the N half-life during HD was about 5 h, whereas during H HDF it was less than 2.5 h, approaching that reported in normal subjects. N half-life out of dialysis treatments was about 55 h. In conclusion, N pharmacokinetics are strikingly different between H HDF and HD, with N clearance during H HDF about the double of that during HD. The implications of this study are: a different dosage adjustment of aminoglycosides is needed for patients routinely treated by HDF; HDF may be a very effective treatment for the overdose of many drugs.

Plasma volume changes induced by sequential ultrafiltration-hemodialysis and sequential hemodialysis-ultrafiltration.

Isolated ultrafiltration (UF) has been shown to preserve plasma volume (PV) by means of a high plasma refilling rate, mediated by a rapid rise in oncotic pressure. This mechanism contributes to the good tolerance of sequential ultrafiltration-hemodialysis (SUH). This study compared PV changes induced by SUH and sequential hemodialysis-ultrafiltration (SHU). Seven dialysis patients underwent two sets of SUH and SHU, in which 2 h of UF (approximately equal to 3L) respectively preceded or followed 2 h of no-weight-change hemodialysis (ISO HD). VEM (volume of extravascular mobilization), VEM/VUF (percent of plasma refilling rate) and delta PV were calculated by mathematical formulas. Results showed: 1) a high VEM/VUF during the UF period, either before or after ISO HD: 80 and 77% respectively; 2) a significant increase in PV during ISO HD after UF, compared to ISO HD before UF: + 229 ml and + 43 ml, P less than 0.05; 3) VEM/VUF significantly higher during SUH than during SHU: 87 and 80%, P less than 0.01. In conclusion, the decrease in PV was lower in SUH than in SHU (11 vs. 19%, P less than 0.001) because the plasma refilling persisted through the ISO HD period.