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Abstract Background Sex differences with regard to clinical manifestations and response to tumor necrosis factor inhibitors (TNFi) have been delineated for the radiographic form of axial spondyloarthritis (axSpA). More limited evidence for a differential effectiveness of treatment in genders exists for the nonradiographic disease state (nr-axSpA). The aim of the study was to compare demographics, clinical parameters, and response to TNFi in women versus men with nr-axSpA. Methods We compared disease characteristics of 264 women and 231 men with nr-axSpA at inclusion in the prospective Swiss Clinical Quality Management Cohort. Response to a first TNFi was assessed in 85 women and 78 men without diagnosed co-morbid fibromyalgia. The primary outcome was the proportion of patients achieving the 40% improvement in the Assessment of SpondyloArthritis international Society criteria (ASAS40) at 1 year. Additional response outcomes were evaluated as secondary outcomes. Patients having discontinued TNFi were considered non-responders. Logistic regression analyses were adjusted for baseline differences, which might potentially mediate the effect of sex on treatment response. Results Compared to men, women had a longer diagnostic delay, a higher level of perceived disease activity, and more enthesitis and were in a lower percentage HLA-B27 positive. An ASAS40 response was achieved by 17% of women and 38% of men (OR 0.34; 95% CI 0.12, 0.93; p = 0.02). A significantly lower response rate in women was confirmed in the adjusted analysis (OR 0.19; 95% CI 0.05, 0.62; p = 0.009) as well as for the other outcomes assessed. Conclusion Despite only few sex differences in patient characteristics in nr-axSpA, response rates to TNFi are significantly lower in women than in men.

Background: Conditioning is a key mechanism of placebo and nocebo effects in adults. Little is known about the underlying mechanisms of placebo and nocebo effects in youth and how they might be influenced by conscious awareness and cognitive abilities. In this study, the role of conditioning on thermal perception in youth was investigated.Methods: Differences in thermal ratings were assessed in response to consciously and non-consciously perceived cues that were conditioned to either low or high heat. Furthermore, we tested whether executive function mediates the effect of conditioning on thermal perception. Thirty-five high-school students (14–17 years) completed an executive function task and underwent a sensory perception paradigm. In a conditioning phase, two distinct neutral faces (conditioned cues) were coupled to either a low or a high temperature stimulus delivered to participants' forearms. In a testing phase, the conditioned cues, and novel faces (non-conditioned control cues), were paired with identical moderate thermal stimuli. In this testing phase, for half of the participants cues were presented consciously (supraliminally) and for the other half non-consciously (subliminally).Results: We found a significant main effect of cue type on thermal ratings (p = 0.003) in spite of identical heat being administered following all cues. Post-hoc analyses indicated that the nocebo-like effect (conditioned high cue compared to control) was significant (p = 0.027); the placebo-like effect (conditioned low cue compared to control) was non-significant. No difference between cues presented supra- vs. subliminally and no significant interaction effects were found. The association between sensory discrimination and the magnitude of the nocebo-like effect was mediated by executive function.Conclusions: To our best knowledge, this is the first study establishing a relationship between thermal perception, nocebo effects, and executive function in youth. Our results may have important implications for understanding cognitive/ learning processes involved in nocebo effects.

Aims: To examine the prognostic value of F-18 fluorodeoxyglucose (FDG) uptake in the bone marrow (BM) for disease recurrence and survival in patients with oropharyngeal squamous cell carcinoma (OP-SCC). The secondary aims were to evaluate the prognostic value of PET/CT parameters for the primary oropharyngeal tumor and total tumor burden, and to assess the correlation between FDG uptake variables and serum inflammatory markers., Methods: This was an observational study of 91 patients with OP-SCC who underwent pretreatment FDG-PET/CT. The patients' blood samples were collected before treatment, and treatment was administered with the intention to cure. The median follow-up time was 40 months. The PET parameters measured were SUV mean BM for the assessment of BM FDG uptake, SUV mean , SUV max , total lesion glycolysis (TLG), and metabolic tumor volume (MTV) for the evaluation of primary oropharyngeal tumor and total tumor burden. Blood samples were analyzed to determine each patient's white cell, red cell, and platelet cell counts, hemoglobin, and C-reactive protein level. In a subgroup of 33 patients, blood serum was analyzed to evaluate the expression of serum immune proteins using a proximity extension assay (Olink Proteomics)., Results: The univariate analysis revealed that SUV mean BM and tumor-specific parameters (SUV max tumor, SUV mean total, SUV max total, MTVtotal, TLGtotal) were significantly associated with recurrence-free survival (RFS). After adjusting for age, sex, and stage only SUV mean BM remained significantly associated with RFS. Spearman's correlation identified several correlations between PET parameters and inflammatory markers., Conclusions: Our results show that several FDG-PET/CT parameters may have a prognostic value of treatment outcome in patients with OP-SCC. However, SUV mean BM was the only independent PET parameter that showed a prognostic value for RFS in the study cohort. Moreover, the study findings might suggest an association between systemic inflammation and the metabolic activity in the BM., (© 2024 The Authors. Head & Neck published by Wiley Periodicals LLC.)

Background: 18 F-NaF positron emission tomography/computed tomography (fluoride PET/CT) is considered the most sensitive technique to detect bone metastasis in prostate cancer (PCa). 68 Ga-PSMA-11 (PSMA) PET/CT is increasingly used for staging of PCa. This study primarily aimed to compare the diagnostic performance of fluoride PET/CT and gallium-based PSMA PET/CT in identifying bone metastasis followed by a comparison of PSMA PET/CT with contrast-enhanced CT (CE-CT) in identifying soft tissue lesions as a secondary objective., Methods: Twenty-eight PCa patients with high suspicion of disseminated disease following curative treatment were prospectively evaluated. PET/CT examinations using fluoride and PSMA were performed. All suspicious bone lesions were counted, and the tracer uptake was measured as standardized uptake values (SUV) for both tracers. In patients with multiple findings, ten bone lesions with highest SUV max were selected from which identical lesions from both scans were considered for direct comparison of SUV max . Soft tissue findings of local and lymph node lesions from CE-CT were compared with PSMA PET/CT., Results: Both scans were negative for bone lesions in 7 patients (25%). Of 699 lesions consistent with skeletal metastasis in 21 patients on fluoride PET/CT, PSMA PET/CT identified 579 lesions (83%). In 69 identical bone lesions fluoride PET/CT showed significantly higher uptake (mean SUV max : 73.1 ± 36.8) compared to PSMA PET/CT (34.5 ± 31.4; p < 0.001). Compared to CE-CT, PSMA PET/CT showed better diagnostic performance in locating local (96% vs 61%, p = 0.004) and lymph node (94% vs 46%, p < 0.001) metastasis., Conclusion: In this prospective comparative study, PSMA PET/CT detected the majority of bone lesions that were positive on fluoride PET/CT. Further, this study indicates better diagnostic performance of PSMA PET/CT to locate soft tissue lesions compared to CE-CT., (© 2022. The Author(s).)

Positron emission tomography (PET) imaging is used to localize recurrent disease in prostate cancer (PCa). The tracer 68 Ga-PSMA-11 visualizes lesions overexpressing prostate-specific membrane antigen (PSMA), while 11 C-acetate visualizes lesions with increased anabolic metabolism. The aim of this study was to compare the performance of PSMA-PET and acetate-PET in re-staging patients with biochemical relapse. Thirty PCa patients with prostate-specific antigen (PSA) relapse after primary curative therapy were prospectively evaluated. PET/CT examinations using 11 C-acetate and 68 Ga-PSMA-11 were performed. Identified lesions were categorized according to anatomical location and PET measurements were correlated with PSA at time of scan. Tumour lesions showed higher semi-quantitative uptake values on PSMA-PET than acetate-PET. PSMA-PET identified more lesions in 11 patients, fewer lesions in eight patients, and identical number of lesions in 11 patients. This study indicates better diagnostic performance of PSMA-PET, particularly in detecting lymph node (81% vs 60%, p = 0.02) and bone metastasis (95% vs 61%, p = 0.0001) compared to acetate-PET. However, 38% of PSMA-expressing metastases appear to be metabolically inactive and 15% of metabolically active metastases lack PSMA expression. Addition of PET with a metabolic tracer, such as 11 C-acetate, might be beneficial before making treatment decisions.

Purpose : Dynamic [ 11 C]-acetate positron emission tomography (PET) can be used to study tissue perfusion and carbon flux simultaneously. In this study, the feasibility of the quantification of prostate cancer aggressiveness using parametric methods assessing [ 11 C]-acetate kinetics was investigated in prostate cancer subjects. The underlying uptake mechanism correlated with [ 11 C]-acetate influx and efflux measured in real-time in vitro in cell culture. Methods : Twenty-one patients with newly diagnosed low-to-moderate risk prostate cancer underwent magnetic resonance imaging (MRI) and dynamic [ 11 C]-acetate PET/CT examinations of the pelvis. Parametric images of K 1 (extraction × perfusion), k 2 (oxidative metabolism) and V T (=K 1 /k 2 , anabolic metabolism defined as carbon retention) were constructed using a one-tissue compartment model with an arterial input function derived from pelvic arteries. Regions of interest (ROIs) of the largest cancer lesion in each patient and normal prostate tissue were drawn using information from MRI (T2 and DWI images), biopsy results, and post-surgical histopathology of whole prostate sections (n=7). In vitro kinetics of [ 11 C]-acetate were studied on DU145 and PC3 cell lines using LigandTracer ® White equipment for the measurement of the radioactivity uptake in real-time at 37°C. Results : Mean prostate specific antigen (PSA) was 8.33±3.92 ng/mL and median Gleason Sum 6 (range 5-7). K 1 , V T and standardized uptake values (SUVs) were significantly higher in cancerous prostate tissues compared to normal ones for all patients (p<0.001), while k 2 was not (p=0.26). PSA values correlated to early SUVs (r=0.50, p=0.02) and K 1 (r=0.48, p=0.03). Early and late SUVs correlated to V T (r>0.76, p<0.001) and K 1 (r>0.64, p<0.005). In vitro studies demonstrated higher extraction and retention (p<0.01) of [ 11 C]-acetate in the more aggressive PC3 cells. Conclusion : Parametric images could be used to visualize the [ 11 C]-acetate kinetics of the prostate cancer exhibiting elevated extraction associated with the cancer aggressiveness. The influx rate of [ 11 C]-acetate studied in cell culture also showed dependence on the cancer aggressiveness associated with elevated lipogenesis. Dynamic [ 11 C]-acetate/PET demonstrated potential for prostate cancer aggressiveness estimation using parametric-based K 1 and V T values., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Accurate localization of recurrent prostate cancer (PCa) is critical, especially if curative therapy is intended. With the aim to optimize target-to-background uptake ratio in 68 Ga-PSMA-11 PET, we investigated the image quality and quantitative measures of regularized reconstruction by block-sequential regularized expectation maximization (BSREM). Methods: The study encompassed retrospective reconstruction and analysis of 20 digital time-of-flight (TOF) PET/CT examinations acquired 60 min post injection of 2 MBq/kg of 68 Ga-PSMA-11 in PCa patients with biochemical relapse after primary treatment. Reconstruction by ordered-subsets expectation maximization (OSEM; 3 iterations, 16 subsets, 5 mm gaussian postprocessing filter) and BSREM (β-values of 100-1600) were used, both including TOF and point spread function (PSF) recovery. Background variability (BV) was measured by placing a spherical volume of interest in the right liver lobe and defined as the standard deviation divided by the mean standardized uptake value (SUV). The image quality was evaluated in terms of signal-to-noise ratio (SNR) and signal-to-background ratio (SBR), using SUV max of the lesions. A visual assessment was performed by four observers. Results: OSEM reconstruction produced images with a BV of 15%, whereas BSREM with a β-value above 300 resulted in lower BVs than OSEM (36% with β 100, 8% with β 1300). Decreasing the acquisition duration from 2 to 1 and 0.5 min per bed position increased BV for both reconstruction methods, although BSREM with β-values equal to or higher than 800 and 1200, respectively, kept the BV below 15%. In comparison of BSREM with OSEM, the mean SNR improved by 25 to 66% with an increasing β-value in the range of 200-1300, whereas the mean SBR decreased with an increasing β-value, ranging from 0 to 125% with a β-value of 100 and 900, respectively. Decreased acquisition duration resulted in β-values of 800 to 1000 and 1200 to 1400 for 1 and 0.5 min per bed position, respectively, producing improved image quality measures compared with OSEM at a full acquisition duration of 2 min per bed position. The observer study showed a slight overall preference for BSREM β 900 although the interobserver variability was high. Conclusion: BSREM image reconstruction with β-values in the range of 400-900 resulted in lower BV and similar or improved SNR and SBR in comparison with OSEM., Competing Interests: Competing Interests: A collaborative research agreement between Uppsala University Hospital and GE Healthcare partly financed this study (P.I. ML), covering the salary for EL. The other authors report no disclosures or potential conflicts of interest.

Purpose: Malignant de novo lipogenesis is strongly linked to the aggressiveness of prostate cancer (PCa) under experimental conditions. 11 C-Acetate PET/CT is a potential noninvasive biomarker of malignant lipogenesis in PCa, but its prognostic value is not known. The objective of this study was to analyse 11 C-acetate PET/CT image metrics in relation to survival., Methods: All patients undergoing 11 C-acetate PET/CT in one university hospital from 2005 to 2011 due to PSA relapse after previous prostatectomy were retrospectively evaluated. Two groups of patients were compared: those who died from PCa and those who were censored. All previously reported findings of local recurrence, regional or distal lymph node metastases and bone metastases were counted and evaluated regarding 11 C-acetate uptake intensity (SUV max ) and tumour volume. Total tumour volume and total lipogenic activity (TLA, summed SUV max  × TV) were calculated. Survival analysis in the entire study population was followed by Cox proportional hazards ratio (HR) analysis., Results: A total of 121 patients were included, and 22 PCa-specific deaths were recorded. The mean PSA level at the time of PET was 2.69 ± 4.35 ng/mL. The median follow-up of the study population was 79 ± 28 months. PET identified at least one PCa lesion in 53 % of patients. Five-year PCa-specific survival after PET was 80 % and 100 % in patients with a positive and a negative PET scan, respectively (p < 0.001). Time-to-death was linearly correlated with highest SUV max (r = -0.55, p = 0.01) and nonlinearly with TLA (r = -0.75, p < 0.001). Multivariate analysis showed statistical significance for number of bone metastases (HR 1.74, p = 0.01), tertile of TLA (HR 5.63, p = 0.029) and postoperative Gleason score (HR 1.84, p = 0.045)., Conclusion: Malignant 11 C-acetate accumulation measured with PET/CT is a strong predictor of survival in the setting of PSA relapse after prostatectomy. The study provides further evidence for a quantitative relationship between malignant de novo lipogenesis and early death. 11 C-Acetate PET/CT might be useful for identifying a high-risk population of relapsing patients in which therapies targeting malignant lipogenesis might be of particular benefit.