Reingard Aigner

Effect of extracorporeal liver support by MARS and Prometheus on serum cytokines in acute-on-chronic liver failure

IntroductionCytokines are believed to play an important role in acute-on-chronic liver failure (ACLF). Extracorporeal liver support systems may exert beneficial effects in ACLF via removal of cytokines. At present, two systems are commercially available, the Molecular Adsorbent Recirculating System (MARS™) and Fractionated Plasma Separation, Adsorption and Dialysis (Prometheus™). The aim of this study was to compare the effects of MARS and Prometheus treatments on serum cytokine levels and their clearances.MethodsEight patients with ACLF underwent alternating treatments with either MARS or Prometheus in a randomized cross-over design. Thirty-four treatments (17 MARS, 17 Prometheus) were available for analysis. Serum cytokines were measured before and after each treatment, and cytokine clearance was calculated from paired arterial and venous samples and effective plasma flow one hour after the start of treatment.ResultsBaseline serum levels of interleukin (IL)-6, IL-8, IL-10, tumor necrosis factor-alpha (TNF-α), and soluble TNF-α receptor 1 were significantly elevated in patients with ACLF. Measurable plasma clearances were detected for all cytokines tested, but no significant changes in serum levels of any cytokine were found after treatments with MARS or Prometheus. In MARS treatments, IL-10 was cleared from plasma more efficiently than IL-6. Clearance of IL-10 was higher in Prometheus than in MARS treatments.ConclusionCytokines are cleared from plasma by both MARS and Prometheus, but neither system is able to change serum cytokine levels. This discrepancy is probably due to a high rate of cytokine production in patients with ACLF.

The Effect of a Single Infusion of Zoledronic Acid on Early Implant Migration in Total Hip Arthroplasty A Randomized, Double-Blind, Controlled Trial

BACKGROUNDnAseptic loosening is the most frequent cause of implant failure in total hip arthroplasty. While a direct link between aseptic loosening and periprosthetic bone loss remains elusive, there is plentiful evidence for a close association with early implant migration. The present trial was primarily designed to evaluate whether a single infusion of 4 mg of zoledronic acid prevented early implant migration in patients with osteonecrosis of the femoral head.nnnMETHODSnFifty patients were consecutively enrolled to receive either zoledronic acid or saline solution after cementless total hip arthroplasty. Radiographs, biochemical parameters of bone turnover, and the Harris hip-rating score were determined preoperatively and at each follow-up examination at seven weeks, six months, one year, and yearly thereafter. The median follow-up period was 2.8 years.nnnRESULTSnWe found a significant subsidence of the stem of up to a mean (and standard deviation) of -1.2 +/- 0.6 mm at two years within the control group, and the cups had a mean medialization of 0.6 +/- 1.0 mm and a mean cranialization of 0.6 +/- 0.8 mm (p < 0.001). Treatment with zoledronic acid effectively minimized the migration of the cups in both the transverse and the vertical direction (mean, 0.15 +/- 0.6 mm and 0.06 +/- 0.6 mm, respectively; p < 0.05), while only a trend to decreased subsidence of the stem was detected. Finally, the Harris hip score rapidly increased over time in both treatment groups, although this increase was significantly more pronounced in the zoledronate-treated group than in the control group (analysis of variance, p = 0.008).nnnCONCLUSIONSnA single infusion of zoledronic acid shows promise in improving initial fixation of a cementless implant, which may improve the clinical outcome of total hip arthroplasty in patients with osteonecrosis of the femoral head.

Vitamin E kinetics in smokers and nonsmokers

Does cigarette smoking increase vitamin E utilization in vivo? A trial was carried out in 6 smokers and 5 nonsmokers of comparable ages and serum lipids. Subjects consumed 75 mg each d(3)-RRR and d(6)-all rac-alpha-tocopheryl acetates (natural and synthetic vitamin E, respectively) daily for 7 d with a standardized breakfast. Fasting blood samples were drawn on days -7, -6, -5, -4, -3, -2, -1, 0, 1, 2, 3, 4, 5, 6, 7, 9, 14, 21 (negative days indicate supplementation). In both groups, plasma d(3)-alpha-tocopherol concentrations were approximately double of d(6)-alpha-tocopherol. At day 0, the %d(3) alpha-tocopherols (d(3)-alpha-tocopherol/total-alpha-tocopherol x 100) were similar in both smokers and nonsmokers. Subsequently, there was a trend toward a faster exponential disappearance of the plasma %d(3) alpha-tocopherol in smokers compared with nonsmokers (0.30 +/- 0.04 compared with 0.24 +/- 0.05, p =.0565). The calculated %d(3) half-lives were 55.6 +/- 7.4 h in smokers and 72.1 +/- 17.3 h in nonsmokers (p =.0630). By day 21, the %d(3) in smokers had decreased to 1.4% +/- 0.3% while it was 2.2% +/- 0.7% (p =.0418) in the nonsmokers. These data suggest that smoking increases plasma vitamin E disappearance, but further studies are needed to confirm this finding and to assess its cause.

Is there a place for FET PET in the initial evaluation of brain lesions with unknown significance

PurposeThe aim of this study was to evaluate the clinical value of the use of O-(2-[18F]fluoroethyl)-l-tyrosine (FET) positron emission tomography (PET)/computed tomography (CT) in patients of a neurological clinic for evaluation of brain lesions newly diagnosed by magnetic resonance imaging (MRI).MethodsWe evaluated 88 patients (44 women and 44 men) with a mean age of 50u2009±u200919xa0years who were sent consecutively for evaluation of an intracerebral mass or lesion observed by MRI from 2006 to 2008. Hospitalization was necessary due to neurological clinical symptoms. Images were obtained by PET/CT 30xa0min after i.v. injection of 185xa0MBq FET. Coregistration with MRI was done by HERMES workstation.ResultsFET uptake above the cortical level was observed in 60 patients. Neurosurgery was performed in 60 patients (51 with FET-positive imaging); 36 high-grade and 19 low-grade tumours were verified histologically. The sensitivity of FET PET for high-grade tumours (WHO III–IV) was 94% in this setting. Among the low-grade brain tumours (WHO I–II) 13 of 19 were FET positive, which indicates a sensitivity of 68%. Five of ten (50%) astrocytomas I and II could not be visualized by FET. Histological data were not provided for 28 of 88 patients, so the diagnostic approach is based upon longitudinal observation. Radiological and/or clinical control was done at a median of 7xa0months later. Three patients (all FET positive) died a few months after the examination because of rapid progression of the malignant brain tumour. A malignant entity could be excluded in the other 25 patients. Considering the whole cohort of 88 patients, 43 patients with malignant tumour could be identified, including high-grade glioma, intracerebral lymphoma (nu2009=u20091) and metastasis (nu2009=u20093). The sensitivity of FET PET for detecting a malignant tumour entity was 93%. We observed two false-positive cases with postischaemic lesions. Remarkably, the two patients with cerebral gliomatosis were false-negative on FET PET imaging. The negative predictive value for a malignant entity was calculated to be 89%.ConclusionOur results indicate a high sensitivity of FET PET for detecting high-grade glioma in patients with neurological symptoms and recently observed brain lesions by MRI. In the setting of evaluating new brain lesions of unknown significance via FET PET a negative image can encourage a wait and see strategy—of course in accordance with the clinical picture and morphological imaging.

Intraoperative control of resection margins in advanced head and neck cancer using a 3D-navigation system based on PET/CT image fusion

Local recurrent of disease in advanced carcinomas of the head and neck is strongly correlated with the presence of positive or close resection margins after operative treatment. The purpose of this study is to present a new method of assessing resection margins intraoperatively using image-guided surgery based on positron emission tomography/computed tomography (PET/CT) image fusion. In 6 patients who underwent surgical treatment of head and neck stage for T4a-T4b carcinomas PET/CT image fusion was done on the workstation of a 3D-navigation system. Intraoperative image-guided navigation of the defect following surgical ablation of the tumour was performed in every patient. Intraoperative navigation of the ablative defect showed an unsafe resection margin in 4 patients. In three of these patients additional image-guided resection allowed local control of the tumour to be achieved. In one patient additional resection was not possible due to skull base invasion. The histopathological exam of the four tumour specimens confirmed positive or close resection margins. The current results suggest that intraoperative control of the surgical margins using a 3D-navigation system based on PET/CT image fusion can be a useful tool to assess and improve local control in advanced cancer of the head and neck.

The 936C>T polymorphism of the gene for vascular endothelial growth factor is associated with 18F-fluorodeoxyglucose uptake

Background: Positron emission tomography (PET) is a an important technology for detection and staging of breast cancer. The method is based upon assessment of glucose metabolism using the 18F-fluorodeoxyglucose (18F-FDG) as glucose analog. A strong variability of 18F-FDG uptake by breast cancer tissue has been reported, the reason for which is not fully understood but may involve vascular density and integrity. A 936C>T polymorphism in the gene for the vascular endothelial growth factor (VEGF) has been associated with VEGF plasma levels and breast cancer risk.Methods: To analyze the role of this polymorphism for 18F-FDG uptake in breast cancer patients, we determined the VEGF genotype in 37 patients in whom PET was performed for detection of metastases. An 18F-FDG uptake score of 1 (low uptake), 2 (medium uptake) or 3 (high uptake) was assigned to each patient.Results: VEGF CC, CT and TT genotypes were found in 28, 8 and 1 patient. Uptake score of 1 was found in three patients, score 2 in 12 patients and score 3 in 22 patients. VEGF genotype was significantly associated with FDG uptake score (χ2 test, p=0.007). The number of 936-T alleles correlated with a lower 18F-FDG uptake score (Spearman correlation test, p=0.032).Conclusion: In the present study the common VEGF 936C>T polymorphisms had a major impact on 18F-FDG uptake in breast cancer patients. If this result can be confirmed in following studies, it might have strong relevance for the use of PET as diagnostic tool.

Effects of weight loss on leptin, sex hormones, and measures of adiposity in obese children.

Adipose tissue influences steroid conversion by paracrine and autocrine mechanisms. Leptin is secreted by adipocytes and influenced by sex hormones and adiposity. Short-term weight loss in the treatment of childhood obesity reduces leptin and adipose tissue. We therefore asked, Do alterations in sex hormones occur owing to weight loss? and can these alterations be explained by changes in fat mass or sc fat and are alterations in sex hormones directly related to the fall in leptin? Twenty obese boys and 40 obese girls were studied before and after 3 wk of low-calorie diet and physical activity. The weight loss program significantly lowered fat mass, abdominal fat distribution, sc fat (all p<0.0001), leptin, insulin, and estradiol (all p<0.0001) but not testosterone. Changes in leptin were related to changes in body mass and to changes in fat mass in boys. In girls, changes in leptin were related to changes in sc fatness and also to changes in insulin. In boys, the reduction in sc fat was positively correlated to changes in testosterone (r=0.54; p<0.01) and inversely related to the fall in estradiol (r=−0.41; p<0.05). In girls, changes in testosterone (r=0.33; p<0.05) and in estradiol (r=0.40; p<0.001) were related to changes in insulin. Stepwise regression showed that initial leptin was the best determinant for the fall in leptin (adjusted R2=0.87; p<0.0001). The results show that alterations in sex hormones are related to changes in certain fat depots in boys where as in girls changes in insulin might participate in changes in sex hormones. A greater fall in leptin owing to short-term weight loss is not associated with greater alterations in sex hormones and initial leptin is the best determinant to explain the variability in changes in leptin. The possibility of sex differences in changes in sex hormones secondary to the reduction in fatness warrants further study.

Diagnosis of bone infection using 99mTc-HMPAO labelled leukocytes

In order to evaluate the importance of 99mTc-hexamethylpropylene amine oxime (99mTc-HMPAO) leukocyte scintigraphy in the diagnosis of bone infection, we retrospectively reviewed 324 patients. Abnormal findings were seen in 221 patients. In the other 103 cases acute pathological inflammation could be ruled out. The patients with pathological findings were divided into four groups according to the location of the infection. This method showed the localizations of skeletal disorders and its differences to other diagnostic imaging modalities. The underlying abnormalities causing the inflammation were determined. In conclusion, 99mTc-HMPAO leukocyte scintigraphy is still a very sensitive method for either whole body screening or local detection of acute or exacerbated chronic osteomyelitis. The advantages of this method over other diagnostic imaging methods are shown.

Parathyroid scintigraphy: comparison of technetium-99m methoxyisobutylisonitrile and technetium-99m tetrofosmin studies

We report the preliminary results of a prospective study demonstrating tetrofosmin uptake in surgically and histologically proven parathyroid adenomas. In ten patients with primary chronic hyperparathyroidism, parathyroid imaging was performed using (1) technetium-99m methoxyisobutylisonitrile (MIBI) and (2)99mTc-1,2-bis(bis(2-ethoxyethyl)phosphino)ethane (tetrofosmin) within a time interval of 3–5 days. Both tracers correctly identified the parathyroid adenomas by focal prolonged tracer retention. On visual inspection image contrast was generally higher with MIBI than with tetrofosmin in all the patients studied. Tetrofosmin showed a slower elimination from the parathyroid adenomas than MIBI in six of the ten cases. Our preliminary results show that tetrofosmin, like MIBI, as a feasible, sensitive tracer for parathyroid scintigraphy. For routine use, the rapid kit preparation without heating and the lower radiation dose to the patient make tetrofosmin an alternative tracer for parathyroid scintigraphy. Further evaluation is needed to determine which of the two tracers is the more sensitive for the detection of parathyroid adenomas, and which tracer properties better reflect the degree of endocrine activity.[/p]

Digital image fusion of CT and PET data sets--clinical value in abdominal/pelvic malignancies.

PURPOSEnWe investigated the clinical relevance of digital image fusion of CT and 2-[18F]fluoro-2-deoxy-D-glucose ([18F]FDG) positron emission tomography (PET) studies in patients with suspected abdominal and/or pelvic metastasis.nnnMETHODnNineteen patients with suspected residual/recurrent malignancies underwent CT and [18F]FDG PET studies of the abdomen and/or pelvis. The data sets of both modalities were fused on a digital workstation by automatic adaptation of the pixel size and the slice thickness. Different body positions were corrected by semiautomatic adaptation of the body axes. The fused images were reconstructed in sagittal, coronal, and axial planes.nnnRESULTSnGood spatial correlation between both modalities was achieved in all patients. Image fusion improved the spatial allocation of pathologically increased [18F]FDG uptake in 7 of 35 lesions (20%).nnnCONCLUSIONnThis work suggests that digital image fusion of CT and [18F]FDG PET data sets improves the anatomical localization of foci with increased [18F]FDG enhancement of the retroperitoneum and the abdominal/pelvic wall, respectively.