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  • Hua, Ay-Yen, et al. (författare)
  • Mapping functions in health-related quality of life: mapping from the Achilles Tendon Rupture Score to the EQ-5D.
  • 2018
  • Ingår i: Knee surgery, sports traumatology, arthroscopy : official journal of the ESSKA. - 1433-7347. ; 26:10, s. 3083-3088
  • Tidskriftsartikel (refereegranskat)abstract
    • Health state utility values are derived from preference-based measurements and are useful in calculating quality-adjusted life years (QALYs), which is a metric commonly used in cost-effectiveness studies. The purpose of this study was to convert the Achilles Tendon Rupture Score (ATRS) to the preference-based European Quality of Life-5 Dimension Questionnaire (EQ-5D) by estimating the relationship between the two scores using mapping.Data were collected from a randomised controlled trial, where 100 patients were treated either surgically or non-surgically for Achilles tendon rupture. Forty-three and forty-four patients in surgical group and non-surgical group completed the ATRS and the EQ-5D alongside each other during follow-up at three time points. Different models of the relationship between the ATRS and the EQ-5D were developed and analysed based on direct mapping and cross-validation. The model with the lowest mean absolute error was observed as the one with the best fit.Among the competing models, mapping based on using a combination of the ATRS items four, five, and six associated with limitation due to pain, during activities of daily living and when walking on uneven ground, produced the best predictor of the EQ-5D score.The present study provides a mapping algorithm to enable the derivation of utility values directly from the ATRS. This approach makes it feasible for researchers, as well as medical practitioners, to obtain preference-based values in clinical studies or settings where only the ATRS is being administered. The algorithm allows for the calculation of QALYs for use in cost-effectiveness analyses, making it valuable in the study of acute Achilles tendon ruptures.II.
  • Huang, Chaorui, et al. (författare)
  • Voxel- and VOI-based analysis of SPECT CBF in relation to clinical and psychological heterogeneity of mild cognitive impairment.
  • 2003
  • Ingår i: NeuroImage. - 1053-8119. ; 19:3, s. 1137-1144
  • Tidskriftsartikel (refereegranskat)abstract
    • This study aimed to explore the heterogeneity of mild cognitive impairment (MCI) and detect differences in regional cerebral blood flow (rCBF) and cognitive function between progressive mild cognitive impairment (PMCI) and stable mild cognitive impairment (SMCI) in order to identify specific changes useful for early diagnosis of dementia. SPECT was performed in 82 MCI subjects and 20 controls using Tc-99m hexamethylpropyleneamine oxime. Cognitive functions were tested in five domains which included episodic memory, semantic memory, visuospatial function, attention, and general cognitive function. After the initial examination, MCI subjects were clinically followed for an average of 2 years. Twenty-eight subjects progressed to dementia and were defined as PMCI at baseline and 54 subjects remained stable and were defined as SMCI at baseline. The baseline rCBF and cognitive function of PMCI, SMCI, and controls were compared. PMCI had decreased relative rCBF in the parietal lobes and increased relative rCBF in prefrontal cortex compared to SMCI and controls at baseline. The cognitive function of PMCI was more severely impaired compared to SMCI with respect to episodic memory and visuospatial and general cognitive function. Both SPECT and neuropsychological tests had moderate discriminant function between PMCI and SMCI at baseline with the area under the receiver operating characteristic (ROC) curve at 75–77%. The combination of these two methods improved the diagnostic accuracy with the area under the ROC curve at 82–84%. Semantic memory and attention were negatively correlated with left prefrontal relative rCBF among the study population. The results show that the clinical heterogeneity of MCI is reflected in different patterns of psychological and CBF changes. Combined SPECT investigation and neuropsychological testing might predict the future development of dementia in patients with MCI.
  • Högberg, Carl, et al. (författare)
  • Succinate independently stimulates full platelet activation via cAMP and PI3β kinase signaling.
  • 2011
  • Ingår i: Journal of Thrombosis and Haemostasis. - Wiley-Blackwell. - 1538-7933. ; 9:2, s. 361-372
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The citric cycle intermediate succinate has recently been identified as ligand for the G-protein coupled receptor (GPCR) SUCNR1. We have previously found that this receptor is one of the most expressed GPCRs in human platelets. Objective: The aim of this study was to investigate the role of SUCNR1 in platelet aggregation and to explore the signalling pathways of this receptor in platelets. Methods and Results: Using RT-PCR, we could demonstrate that SUCNR1 is expressed in human platelets at a level corresponding to that of the P2Y(1) receptor. Light transmission aggregation experiments showed a dose-dependent aggregation induced by succinate reaching a maximum response at 0.5mM. The effect of succinate on platelet aggregation was confirmed with flow cytometry showing increased surface expression of activated GPIIb/IIIa, and P-selectin. Intracellular SUCNR1 signalling was found to result in decreased cAMP levels, Akt phosphorylation mediated by PI3Kβ activation and receptor desensitisation. Further, succinate-induced platelet aggregation was demonstrated to depend on Src, generation of thromboxane A(2) and ATP release. The platelet SUCNR1 is subject to desensitization through both homologous and heterologous mechanisms. In addition, the P2Y(12) receptor inhibitor ticagrelor completely prevented platelet aggregation induced by succinate. Conclusions: Our experiments show that succinate induces full aggregation of human platelets via SUCNR1. Succinate-induced platelet aggregation depends on thromboxane A(2) generation, ATP release and P2Y(12) activation.
  • Högberg, Jonas, 1976-, et al. (författare)
  • Bremsstrahlung imaging of 90Y microspheres shows poor resemblance with distributions of 99mTc-MAA in liver
  • 2010
  • Ingår i: Journal of the European Society of Therapeutic Radiology and Oncology. - 0167-8140. ; 94:1, s. 25-26
  • Konferensbidrag (övrigt vetenskapligt)abstract
    • PURPOSE To study the resemblance between the distributions of pre- therapeutic 99mTc-MAA and therapeutic 90Y-microspheres, used for ra- dioembolization of liver tumours, making use of gamma- and bremsstrahlung imaging. Furthermore, to establish the accuracy of this method by compar- isons of spatial resolution and radioactivity, performed on line source in water phantom and on resected tumour and normal liver from patients previously treated with 90Y-microspheres. MATERIALS 3 patients diagnosed with liver tumours and planned for surgery; 1 with hepatocellular carcinoma and 2 with cholangiocarcinoma, were treated with SIRTEX R © 90Y-microspheres after standard diagnostic SPECT/CT imag- ing with 99mTc-MAA. The images acquired with gamma camera were com- pared regarding distributions of radioactivity; gamma radiation from the 99mTc-MAA distributions and bremsstrahlung from the distributions of 90Y- microspheres (the latter with a wide bremsstrahlung energy window). Resec- tions of tumour- and some normal liver tissues were performed on all three patients; the resected tissues were sliced, smaller samples were punched out and the radioactivity was measured with a NaI-detector. Furthermore, autoradiography was performed on some slices. A line source with the in- ner diameter 1 mm was positioned in a cylindrical water phantom with the diameter 20 cm; first the line source was filled with 99mTc, then emptied and filled with 90Y. SPECT/CT imaging was performed on both line source se- tups. The spatial resolutions for both radionuclides were then compared. The results from the imaging comparisons performed on the patients were then evaluated with the complementary radiological methods described above. RESULTS The comparison of images from 99mTc-MAA and 90Y showed a considerable deviance in activity distribution for two of the patients. One ex- ample is shown in the figure, the upper image showing 99mTc-MAA and the lower showing 90Y-microspheres. The moderate difference in spatial resolu- tions for 99mTc and 90Y, (15 vs 18 mm FWHM) confirmed the accuracy of these findings. The other radiological methods did also confirm the macro- scopic activity distribution as shown with bremsstrahlung imaging. CONCLUSIONS Bremsstrahlung imaging is a satisfying and reliable method in showing the actual macroscopic distribution of therapeutic 90Y-microspheres used for radioembolization of liver tumours. The results further demonstrate the need for a better diagnostic method than the one currently used, with 99mTc-MAA, thereby providing a better pre-dosimetry; hopefully with a better selection of patients, regarding tumour regression and a lower risk of liver failure.
  • Högberg, Jonas, 1976-, et al. (författare)
  • Heterogeneity of microsphere distribution in resected liver and tumour tissue following selective intrahepatic radiotherapy
  • 2014
  • Ingår i: EJNMMI Research. - 2191-219X. ; 4:48
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND Selective arterial radioembolisation of liver tumours has increased, because of encouraging efficacy reports; however, therapeutic parameters used in external beam therapy are not applicable for understanding and predicting potential toxicity and efficacy, necessitating further studies of the physical and biological characteristics of radioembolisation. The aim was to characterise heterogeneity in the distribution of microspheres on a therapeutically relevant geometric scale considering the range of yttrium-90 (90Y) β-particles. METHODS Two patients with intrahepatic cholangiocarcinoma, marginally resectable, were treated by selective arterial embolisation with 90Y resin microspheres (SIRTEX®), followed 9 days post-infusion by resection, including macroscopic tumour tissue and surrounding normal liver parenchyma. Formalin-fixed, sectioned resected tissues were exposed to autoradiographic films, or tissue biopsies of various dimensions were punched out for activity measurements and microscopy. RESULTS Autoradiography and activity measurements revealed a higher activity in tumour tissue compared to normal liver parenchyma. Heterogeneity in activity distribution was evident in both normal liver and tumour tissue. Activity measurements were analysed in relation to the sample mass (5 to 422 mg), and heterogeneities were detected by statistical means; the larger the tissue biopsies, the smaller was the coefficient of variation. The skewness of the activity distributions increased with decreasing biopsy mass. CONCLUSIONS The tissue activity distributions in normal tissue were heterogeneous on a relevant geometric scale considering the range of the ionising electrons. Given the similar and repetitive structure of the liver parenchyma, this finding could partly explain the tolerance of a relatively high mean absorbed dose to the liver parenchyma from β-particles. Keywords: Radioembolisation; Y-90; SIR; Surgery; Activity heterogeneity
  • Högberg, Jonas, 1976-, et al. (författare)
  • Increased absorbed liver dose in Selective Internal Radiation Therapy (SIRT) correlates with increased sphere-cluster frequency and absorbed dose inhomogeneity
  • 2015
  • Ingår i: EJNMMI Physics. - 2197-7364. ; 2:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background The higher tolerated mean absorbed dose for selective internal radiation therapy (SIRT) with intra-arterially infused 90Y microspheres compared to external beam therapy is speculated to be caused by absorbed dose inhomogeneity, which allows for liver regeneration. However, the complex liver microanatomy and rheology makes modelling less valuable if the tolerance doses are not based on the actual microsphere distribution. The present study demonstrates the sphere distribution and small-scale absorbed dose inhomogeneity and its correlation with the mean absorbed dose in liver tissue resected after SIRT. Methods A patient with marginally resectable cholangiocarcinoma underwent SIRT 9 days prior to resection including adjacent normal liver tissue. The resected specimen was formalin-fixed and sliced into 1 to 2-mm sections. Forty-one normal liver biopsies 6-8 mm in diameter were punched from these sections and the radioactivity measured. Sixteen biopsies were further processed for detailed analyses by consecutive serial sectioning of 15 30-μm sections per biopsy, mounted and stained with haematoxylin-eosin. All sections were scrutinised for isolated or conglomerate spheres. Small-scale dose distributions were obtained by applying a 90Y-dose point kernel to the microsphere distributions. Results A total of 3888 spheres were found in the 240 sections. Clusters were frequently found as strings in the arterioles and as conglomerates in small arteries, with the largest cluster comprising 453 spheres. An increased mean absorbed dose in the punch biopsies correlated with large clusters and a greater coefficient of variation. In simulations the absorbed dose was 5–1240 Gy; 90% were 10-97 Gy and 45% were <30 Gy, the assumed tolerance in external beam therapy. Conclusions Sphere clusters were located in both arterioles and small arteries and increased in size with increasing sphere concentration, resulting in increased absorbed dose inhomogeneity, which contradicts earlier modelling studies.
  • Högberg, Jonas, 1976-, et al. (författare)
  • On the dose heterogeneity in normal liver tissue due to treatment of liver tumors with yttrium-90 microspheres
  • 2012
  • Ingår i: 25th Annual Congress on European Association of Nuclear Medicine, Milano, Italy, October 27-31, 2012. European Journal of Nuclear Medicine and Molecular Imaging. - 1619-7070 .- 1619-7089. ; 39:suppl 2, s. S281-S281
  • Konferensbidrag (övrigt vetenskapligt)abstract
    • Aim: When treating patients with primary or metastatic liver cancer, applying external radiotherapy, an absorbed dose of 30 - 35 Gy to the whole normal liver tissue volume is associated with a 5 % risk of radiation-induced hepatitis. If less than half of the normal liver volume is being exposed, the threshold for a 5 % risk of hepatitis is increased to above 60 Gy for both primary and metastatic liver cancer. Experience with patients treated with SIR-Spheres® (Sirtex Medical Ltd.), resin microspheres aggregated with yttrium-90, has shown that most patients tolerate an average absorbed dose to normal liver tissue higher than 60 Gy. The high tolerance for this treatment procedure can probably be explained by the resulting heterogenic distribution of radioactivity. It is of interest to study the degree of heterogeneity in the distribution of radioactivity in normal liver tissue, in order to explain or even predict the tolerance to radiation. The aim of this study was to describe the degree of heterogeneity by comparing the relative standard deviations of the radioactivity concentration for different sample mass categories. Materials and Methods: Two patients with cholangiocarcinoma were planned for a combined treatment with yttrium-90-aggregated SIR-Spheres followed by surgery 9 days after radiotherapy. According to standard protocol for treatments with SIR-Spheres, the therapies were preceded by Tc-99m-labled Macro aggregated albumin (Tc-99m-MAA) distribution studies for pre-therapeutic dosimetry and lung shunting evaluations. After surgery the resected tissue, containing both tumour and normal tissue, was studied regarding the distribution of radioactivity. Several small circular samples of normal liver tissue were punched out from 2 mm thick slices of resected tissue, deliberately varying the sizes, and thus the masses of the tissue samples (from 6 to 102 mg). The samples were weighed and categorized in two (first patient) and three (second patient) groups, depending on sample mass. After this the radioactivity was measured with a NaI(Tl) detector. The relative standard deviations (SD/Median) for the radioactivity concentration for each sample mass group were determined and compared. Results: The relative standard deviation for the radioactivity concentration was decreasing rapidly with increasing sample mass. Conclusion: The results indicate a considerable degree of heterogeneity in the distribution of microspheres. One probable explanation for this heterogeneity is clustering of microspheres in the blood vessels.
  • Högberg, Jonas, 1976-, et al. (författare)
  • Radiation exposure during liver surgery after treatment with (90)Y microspheres, evaluated with computer simulations and dosimeter measurements.
  • 2012
  • Ingår i: Journal of radiological protection : official journal of the Society for Radiological Protection. - 1361-6498. ; 32:4, s. 439-46
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose. Two patients with liver tumours were planned for a combined treatment, including surgery with preceding injections of β(-) radiation emitting (90)Y microspheres (SIRTEX(®)). The aim of this paper is to present a method of pre-surgical computer simulations of the absorbed dose rate on the surface of tumour tissue, combined with measurements of the actual absorbed dose rate on resected tissue, in order to estimate the absorbed dose to a surgeon's fingers during such surgery procedures. Methods and Materials. The dose rates from β(-) radiation on the surface of tumour tissue were simulated with the software VARSKIN(®) Mod 2. The activity concentrations in tumours were estimated, based on SPECT/CT distribution studies of (99m)Tc-MAA and confirmed by SPECT/CT bremsstrahlung studies of (90)Y microspheres. The activity distributions were considered as homogeneous within the tumour regions. The absorbed dose rates at different tumour tissue spots were calculated based on measurements with thermo-luminescent dosimeters (TLD) fastened on resected tissue. Results. The simulations showed a good agreement with the averaged absorbed dose rates based on TLD measurements performed on resected tissue, differing by 13% and 4% respectively. The absorbed dose rates at the measured maximum hotspots were twice as high as the average dose rates for both patients. Conclusion. The data is not sufficient in order to draw any general conclusions about dose rates on tumour tissue during similar surgeries, neither about the influence of dose rate heterogeneities nor about average dose rates. However, the agreement between simulations and measurements on these limited data indicate that this approach is a promising method for estimations of the radiation exposure to the surgeons' fingers during this kind of surgery procedure. More data from similar surgeries are necessary in order to validate the method.
  • Ihse, Ingemar, et al. (författare)
  • Riktlinjer för handläggning av patienter med pankreascancer
  • 2002
  • Ingår i: Läkartidningen. - Swedish Medical Association. - 0023-7205. ; 99:15, s. 1676-1683
  • Tidskriftsartikel (refereegranskat)abstract
    • Transabdominellt ultraljud är förstahandsundersökning vid misstänkt pankreascancer, följt av spiral-DT eller MR för mer definitiv diagnos. Tumörmarkörer har ingen plats i rutindiagnostiken. Spiral-DT är basen i resektabilitetsbedömningen. Resektion av tumören är en förutsättning för bot. Ett samband har påvisats mellan antalet resektioner som görs vid ett sjukhus årligen och postoperativ mortalitet. Långtidsöverlevnaden efter resektion är oförändrat kort medan postoperativ mortalitet minskat dramatiskt vid enheter som rapporterat sina resultat. Adjuvant behandling efter resektion bör endast ges inom ramen för kliniska studier. Det palliativa omhändertagandet har förbättrats främst genom utveckling inom endoskopi, interventionell radiologi, smärt- och nutritionsbehandling. Palliativ cytostatikabehandling bör endast ges selektivt utanför kliniska studier. Radioterapi har ingen dokumenterad effekt på överlevnaden vid icke-resektabel pankreascancer. Internationellt rekommenderas speciella behandlingsteam för pankreascancer med tillräckliga upptagningsområden (2–4 miljoner invånare).
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