Assessment of bone graft incorporation by 18 F-fluoride positron-emission tomography/computed tomography in patients with persisting symptoms after posterior lumbar interbody fusion

BACKGROUND: Posterior lumbar interbody fusion (PLIF) is a method that allows decompression of the spinal canal and nerve roots by laminectomy combined with fusion by means of intervertebral cages filled with bone graft and pedicle screw fixation. Conventional imaging techniques, such as plain radiography and computed tomography (CT), have limitations to assess bony fusion dynamics. METHODS: In 16 PLIFs of 15 patients with persisting symptoms, positron-emission tomography (PET)/CT scans were made 60 min after intravenous administration of 156 to 263 MBq of (18) F-fluoride, including 1-mm sliced, high-dose, non-contrast-enhanced CT scanning. Maximal standard uptake values (SUVmax) of various regions were calculated and correlated with abnormalities on CT. RESULTS: Subsidence of the cages into the vertebral endplates was the most frequently observed abnormality on CT (in 16 of 27 or 59% of evaluable endplates). Endplate SUVmax values were significantly higher for those patients with pronounced (p < 0.0001) or moderate (p < 0.013) subsidence as compared to those with no subsidence. Additionally, a significant correlation between vertebral and ipsilateral pedicle screw entrance SUVmax values (p < 0.009) was found, possibly indicating posterior transmission of increased bone stress. In our patient group, intercorporal fusion was seen on CT in 63% but showed no correlation to intercorporal SUVmax values. CONCLUSIONS: With the use of (18) F-fluoride PET/CT, intervertebral cage subsidence appeared to be a prominent finding in this patient group with persisting symptoms, and highly correlating with the degree of PET hyperactivity at the vertebral endplates and pedicle screw entry points. Further study using (18) F-fluoride PET/CT should specifically assess the role of metabolically active subsidence in a prospective patient group, to address its role in nonunion and as a cause of persisting pain

Signatures of knee osteoarthritis in women in the temporal and fractal dynamics of human gait

Background: Osteoarthritis of the knee is characterized by progressive cartilage deterioration causing pain and function loss. Symptoms develop late with limited disease-modifying opportunities. Osteoarthritis is a major cause of immobility, with a higher prevalence above 60 years. This age-related increase in prevalence is further amplified by the female gender. Imaging and biochemical analyses for detection of osteoarthritis of the knee are expensive and labor-intensive. Continuous movement tracking could aid in detecting onset and/or worsening of symptoms.Methods: We used portable technology to investigate kinematic differences in female patients with knee osteoarthritis, weight-matched healthy female volunteers and obese female patients with osteoarthritis of the knee. Knee osteoarthritis was established radiographically and corroborated using magnetic resonance imaging.Findings: The total amount, type and level of activity did not differ significantly between groups. The temporal activity pattern during the day was however significantly different with a bimodal signature in healthy volunteers only. Sequence analyses revealed more time to recuperate after dynamic activity in both patient groups. Analysis of walking bouts revealed significant differences in stride interval dynamics, indicative of gait naturalness, only in healthy volunteers. Temporal activity, sequence and walking patterns were independent of body weight.Interpretation: We thus provide for the first-time evidence of temporal specific kinematic signatures in amount and quality of movement also in stride interval dynamics between people with and without osteoarthritis of the knee independent of body weight. These findings could allow early and non-intrusive diagnosis of osteoarthritis enabling concordant treatment.</p

Local bone metabolism during the consolidation process of spinal interbody fusion

INTRODUCTION: Although computed tomography (CT) can identify the presence of eventual bony bridges following lumbar interbody fusion (LIF) surgery, it does not provide information on the ongoing formation process of new bony structures. 18F sodium fluoride (18F-NaF) positron emission tomography (PET) could be used as complementary modality to add information on the bone metabolism at the fusion site. However, it remains unknown how bone metabolism in the operated segment changes early after surgery in uncompromised situations. This study aimed to quantify the changes in local bone metabolism during consolidation of LIF. MATERIALS AND METHODS: Six skeletally mature sheep underwent LIF surgery. 18F-NaF PET/CT scanning was performed 6 and 12 weeks postoperatively to quantify the bone volume and metabolism in the operated segment. Bone metabolism was expressed as a function of bone volume. RESULTS: Early in the fusion process, bone metabolism was increased at the endplates of the operated vertebrae. In a next phase, bone metabolism increased in the center of the interbody region, peaked, and declined to an equilibrium state. During the entire postoperative time period of 12 weeks, bone metabolism in the interbody region was higher than that of a reference site in the spinal column. CONCLUSION: Following LIF surgery, there is a rapid increase in bone metabolism at the vertebral endplates that develops towards the center of the interbody region. Knowing the local bone metabolism during uncompromised consolidation of spinal interbody fusion might enable identification of impaired bone formation early after LIF surgery using 18F-NaF PET/CT scanning

Serotonin and Dopamine Receptor Expression in Solid Tumours Including Rare Cancers

In preclinical studies serotonin stimulates and dopamine inhibits tumour growth and angiogenesis. Information regarding serotonin and dopamine receptor (5-HTR and DRD) expression in human cancers is limited. Therefore, we screened a large tumour set for receptor mRNA overexpression using functional genomic mRNA (FGmRNA) profiling, and we analysed protein expression and location of 5-HTR1B, 5-HTR2B, DRD1, and DRD2 with immunohistochemistry in different tumour types. With FGmRNA profiling 11,756 samples representing 43 tumour types were compared to 3,520 normal tissue samples to analyse receptor overexpression. 5-HTR2B overexpression was present in many tumour types, most frequently in uveal melanomas (56%). Receptor overexpression in rare cancers included 5-HTR1B in nasopharyngeal carcinoma (17%), DRD1 in ependymoma (30%) and synovial sarcoma (21%), and DRD2 in astrocytoma (13%). Immunohistochemistry demonstrated high 5-HTR2B protein expression on melanoma and gastro-intestinal stromal tumour cells and endothelial cells of colon, ovarian, breast, renal and pancreatic tumours. 5-HTR1B expression was predominantly low. High DRD2 protein expression on tumour cells was observed in 48% of pheochromocytomas, and DRD1 expression ranged from 14% in melanoma to 57% in renal cell carcinoma. In conclusion, 5-HTR1B, 5-HTR2B, DRD1, and DRD2 show mRNA overexpression in a broad spectrum of common and rare cancers. 5-HTR2B protein is frequently highly expressed in human cancers, especially on endothelial cells. These findings support further investigation of especially 5HTR2B as a potential treatment target

Use of selective serotonin reuptake inhibitors is associated with very low plasma free serotonin concentrations in humans

Background: Selective serotonin reuptake inhibitors (SSRIs) block the serotonin transporter on neurons, but also on platelets, thus decreasing platelet serotonin concentrations in users of SSRIs. Data on plasma free serotonin concentrations in SSRI users is lacking, while plasma free serotonin is available for receptor binding and plays a role in several pathophysiological processes We therefore measured the plasma free and platelet serotonin concentrations in users of SSRIs and age-matched healthy controls, and we analyzed plasma concentrations of the serotonin precursor tryptophan and serotonin metabolite 5-hydroxyindoleamineacetic acid (5-HIAA). Methods: For this cross-sectional single center case control study, participants were recruited at the departments of Psychiatry and General Medicine. High performance liquid chromatography combined with tandem mass spectrometry (LC-MS/MS) was used to measure plasma free and platelet serotonin, plasma tryptophan and 5-HIAA concentrations. Pre-analytical conditions were optimized by careful blood collection, rapid sample handling, high speed centrifugation, drug and diet restrictions, and age-matched controls. Results: In 64 SSRI users, median concentrations of plasma free and platelet serotonin were 10-fold and 14-fold lower, respectively, than in 64 matched controls. Patients using higher dose SSRIs or those with higher affinity for the serotonin transporter had lower plasma free and platelet serotonin concentrations. Compared to controls, SSRI users had similar median plasma tryptophan concentrations, but slightly higher plasma 5-HIAA concentrations. Conclusion: SSRI users have low platelet serotonin and low plasma free serotonin. This could not be explained by lower concentrations of its precursor tryptophan, and only partially by increased breakdown to 5-HIAA

Effects of intervention with sulindac and inulin/VSL#3 on mucosal and luminal factors in the pouch of patients with familial adenomatous polyposis

Contains fulltext : 97862.pdf (publisher's version ) (Open Access)BACKGROUND/AIM: In order to define future chemoprevention strategies for adenomas or carcinomas in the pouch of patients with familial adenomatous polyposis (FAP), a 4-weeks intervention with (1) sulindac, (2) inulin/VSL#3, and (3) sulindac/inulin/VSL#3 was performed on 17 patients with FAP in a single center intervention study. Primary endpoints were the risk parameters cell proliferation and glutathione S-transferase (GST) detoxification capacity in the pouch mucosa; secondary endpoints were the short chain fatty acid (SCFA) contents, pH, and cytotoxicity of fecal water. METHODS: Before the start and at the end of each 4-week intervention period, six biopsies of the pouch were taken and feces was collected during 24 h. Cell proliferation and GST enzyme activity was assessed in the biopsies and pH, SCFA contents, and cytotoxicity were assessed in the fecal water fraction. The three interventions (sulindac, inulin/VSL#3, sulindac/inulin/VSL#3) were compared with the Mann-Whitney U test. RESULTS: Cell proliferation was lower after sulindac or VSL#3/inulin, the combination treatment with sulindac/inulin/VSL#3 showed the opposite. GST enzyme activity was increased after sulindac or VSL#3/inulin, the combination treatment showed the opposite effect. However, no significance was reached in all these measures. Cytotoxicity, pH, and SCFA content of fecal water showed no differences at all among the three treatment groups. CONCLUSION: Our study revealed non-significant decreased cell proliferation and increased detoxification capacity after treatment with sulindac or VSL#3/inulin; however, combining both regimens did not show an additional effect

Development of West-European PM2.5 and NO2 land use regression models incorporating satellite-derived and chemical transport modelling data

Satellite-derived (SAT) and chemical transport model (CTM) estimates of PM2.5 and NO2 are increasingly used in combination with Land Use Regression (LUR) models. We aimed to compare the contribution of SAT and CTM data to the performance of LUR PM2.5 and NO2 models for Europe. Four sets of models, all including local traffic and land use variables, were compared (LUR without SAT or CTM, with SAT only, with CTM only, and with both SAT and CTM). LUR models were developed using two monitoring data sets: PM2.5 and NO2 ground level measurements from the European Study of Cohorts for Air Pollution Effects (ESCAPE) and from the European AIRBASE network. LUR PM2.5 models including SAT and SAT+CTM explained ~60% of spatial variation in measured PM2.5 concentrations, substantially more than the LUR model without SAT and CTM (adjR(2): 0.33-0.38). For NO2 CTM improved prediction modestly (adjR(2): 0.58) compared to models without SAT and CTM (adjR(2): 0.47-0.51). Both monitoring networks are capable of producing models explaining the spatial variance over a large study area. SAT and CTM estimates of PM2.5 and NO2 significantly improved the performance of high spatial resolution LUR models at the European scale for use in large epidemiological studies