Assessment of a one-week ketogenic diet on brain glycolytic metabolism and on the status epilepticus stage of a lithium-pilocarpine rat model.

The ketogenic diet (KD) has been shown to be effective in refractory epilepsy after long-term administration. However, its interference with short-term brain metabolism and its involvement in the early process leading to epilepsy remain poorly understood. This study aimed to assess the effect of a short-term ketogenic diet on cerebral glucose metabolic changes, before and after status epilepticus (SE) in rats, by using [18F]-FDG PET. Thirty-nine rats were subjected to a one-week KD (KD-rats, n = 24) or to a standard diet (SD-rats, n = 15) before the induction of a status epilepticus (SE) by lithium-pilocarpine administrations. Brain [18F]-FDG PET scans were performed before and 4 h after this induction. Morphological MRIs were acquired and used to spatially normalize the PET images which were then analyzed voxel-wisely using a statistical parametric-based method. Twenty-six rats were analyzed (KD-rats, n = 15; SD-rats, n = 11). The 7 days of the KD were associated with significant increases in the plasma ß-hydroxybutyrate level, but with an unchanged glycemia. The PET images, recorded after the KD and before SE induction, showed an increased metabolism within sites involved in the appetitive behaviors: hypothalamic areas and periaqueductal gray, whereas no area of decreased metabolism was observed. At the 4th hour following the SE induction, large metabolism increases were observed in the KD- and SD-rats in areas known to be involved in the epileptogenesis process late-i.e., the hippocampus, parahippocampic, thalamic and hypothalamic areas, the periaqueductal gray, and the limbic structures (and in the motor cortex for the KD-rats only). However, no statistically significant difference was observed when comparing SD and KD groups at the 4th hour following the SE induction. A one-week ketogenic diet does not prevent the status epilepticus (SE) and associated metabolic brain abnormalities in the lithium-pilocarpine rat model. Further explorations are needed to determine whether a significant prevention could be achieved by more prolonged ketogenic diets and by testing this diet in less severe experimental models, and moreover, to analyze the diet effects on the later and chronic stages leading to epileptogenesis.

18F- FDG PET/CT in reclassifying the probable diagnosis of IE - A review.

In the diagnosis of infective endocarditis (IE), Modified Duke's criteria, coupled with clinical suspicion, serve as the guiding framework. For cases involving prosthetic valve endocarditis and infections affecting implantable devices, the use of metabolic imaging with 18 F-FDG PET/CT scans has gained prominence, as per the recommendations of the European Society of Cardiology guidelines. This imaging modality enhances sensitivity and specificity by identifying infective foci within the heart and extracardiac locations. Early utilization of these scans is crucial for confirming or ruling out IE, although caution is required to mitigate false positive responses, especially in the presence of ongoing inflammatory activity. A standardized ratio of ≥2.0 between FDG uptake around infected tissues and the blood pool has demonstrated a sensitivity of 100 % and specificity of 91 %. It is noteworthy that the sensitivity of FDG PET/CT varies, being lower for native valve and lead infections but considerably higher for prosthetic valve and pulse generator infections. This review provides a comprehensive overview of the advantages offered by FDG PET/CT in achieving a definitive diagnosis of IE.

Prevention of activated brown adipose tissue on 18F-FDG-PET scans of young lymphoma patients: results of an ancillary study within the EuroNet-PHL-C2 trial.

Activated brown fat (aBAT) is known to affect the evaluation of 18F-FDG PET scans, especially in young patients. The aim of this study was to determine factors influencing the occurrence of aBAT, and to investigate the effectiveness of the two preventive measures, warming and beta-blocker (propranolol) administration. Five-hundred-twenty-eight 18F-FDG-PET scans of 241 EuroNet-PHL-C2 trial patients from 41 nuclear medicine departments in Germany and Czech Republic were screened for aBAT. The occurrence of aBAT was analyzed with patient characteristics (age, sex, body mass index, predisposition to aBAT), weather data at the day of 18F-FDG PET scanning as well as the preventive measures taken. Potentially important factors from univariate analyses were included into a logistic regression model. Warming as a preventive measure was used in 243 18F-FDG-PET scans, propranolol was administered in 36, warming and propranolol were combined in 84, and no preventive measures were taken in 165 scans. Whereas age, sex and body mass index had no clear impact, there was an individual predisposition to aBAT. Logistic regression model revealed that the frequency of aBAT mainly depends on the outside temperature (p = 0.005) and can be effectively reduced by warming (p = 0.004), the administration of unselective beta-blocker or the combination of both. Warming is a simple, cheap and non-invasive method to reduce the frequency of aBAT. However, the effect of warming decreases with increasing outside temperatures. Administration of propranolol seems to be equally effective and provides advantages whenever the positive effect of warming is compromised. The combination of both preventive measures could have an additive effect.

Effect of high-dose glucocorticoid treatment on human brown adipose tissue activity: a randomised, double-blinded, placebo-controlled cross-over trial in healthy men.

BACKGROUND: Glucocorticoids (GCs) are widely applied anti-inflammatory drugs that are associated with adverse metabolic effects including insulin resistance and weight gain. Previous research indicates that GCs may negatively impact brown adipose tissue (BAT) activity in rodents and humans. METHODS: We performed a randomised, double-blinded cross-over trial in 16 healthy men (clinicaltrials.govNCT03269747). Participants received 40 mg of prednisone per day for one week or placebo. After a washout period of four weeks, participants crossed-over to the other treatment arm. Primary endpoint was the increase in resting energy expenditure (EE) in response to a mild-cold stimulus (cold-induced thermogenesis, CIT). Secondary outcomes comprised mean 18F-FDG uptake into supraclavicular BAT (SUVmean) as determined by FDG-PET/CT, volume of the BAT depot as well as fat content determined by MRI. The plasma metabolome and the transcriptome of supraclavicular BAT and of skeletal muscle biopsies after each treatment period were analysed. FINDINGS: Sixteen participants were recruited to the trial and completed it successfully per protocol. After prednisone treatment resting EE was higher both during warm and cold conditions. However, CIT was similar, 153 kcal/24 h (95% CI 40-266 kcal/24 h) after placebo and 186 kcal/24 h (95% CI 94-277 kcal/24 h, p = 0.38) after prednisone. SUVmean of BAT after cold exposure was not significantly affected by prednisone (3.36 g/ml, 95% CI 2.69-4.02 g/ml, vs 3.07 g/ml, 95% CI 2.52-3.62 g/ml, p = 0.28). Results of plasma metabolomics and BAT transcriptomics corroborated these findings. RNA sequencing of muscle biopsies revealed higher expression of genes involved in calcium cycling. No serious adverse events were reported and adverse events were evenly distributed between the two treatments. INTERPRETATION: Prednisone increased EE in healthy men possibly by altering skeletal muscle calcium cycling. Cold-induced BAT activity was not affected by GC treatment, which indicates that the unfavourable metabolic effects of GCs are independent from thermogenic adipocytes. FUNDING: Grants from Swiss National Science Foundation (PZ00P3_167823), Bangerter-Rhyner Foundation and from Nora van der Meeuwen-Häfliger Foundation to MJB. A fellowship-grant from the Swiss National Science Foundation (SNF211053) to WS. Grants from German Research Foundation (project number: 314061271-TRR 205) and Else Kröner-Fresenius (grant support 2012_A103 and 2015_A228) to MR.

Accuracy of pre-operative 18-fluoride fluorodeoxyglucose positron emission tomography (FDG-PET) in predicting lymph node involvement in colon cancer.

BACKGROUND: Accurate staging of colon cancer is imperative in directing treatment and prognostication. Existing literature on pre-operative accuracy of FDG-PET/CT in detecting lymph node disease often combines colon and rectal cancer, examines rectal cancers alone, and rarely assesses colon cancer in isolation. Our aim was to assess pre-operative utility of FDG-PET/CT in detecting lymph node disease in colon cancer. METHODS: A retrospective cohort analysis was performed at a single Australian institution between 2017 and 2022 to identify treatment naive primary colonic tumours. Primary outcome was sensitivity and specificity using formal surgical histopathology as gold standard. Secondary outcomes were patient and tumour factors predictive of FDG-PET/CT positive disease including pre-operative CEA, mismatch repair status, duration to surgery, and tumour T-stage. RESULTS: Three hundred and thirty-nine patients were identified. Thirty-four had pre-operative FDG-PET/CT without neoadjuvant therapy. The mean surgical lymph node harvest was 18 nodes. Twenty-five patients had moderately differentiated tumours. The median duration between FDG-PET/CT and operation was 17 days. Pre-operative FDG-PET/CT suggested positive lymph node involvement in 12 patients. Compared to final lymph node histopathology, FDG-PET/CT had a sensitivity of 53%, specificity of 82%, positive predictive value of 75%, negative predictive value of 64% and accuracy of 68%. There was no significant difference between groups for secondary outcomes. CONCLUSION: FDG-PET/CT has moderate specificity but poor sensitivity in the detection of lymph node involvement in colon cancer. Its utility should likely remain isolated to investigating equivocal lesions or follow up of known PET avid disease.

Pre-discharge 18F-Flourodeoxyglucose uptake pattern following transcatheter aortic-valve replacement and adverse prognostic features in aortic stenosis.

18F-Flourodeoxyglucose positron emission tomography/computed tomography (18F-FDG-PET/CT) has been shown to be of utility in transcatheter aortic valve replacement (TAVR) patients with suspected prosthetic valve endocarditis. In the present study, we sought to analyze the relationship between 18F-FDG-PET/CT performed before discharge in TAVR patients and adverse prognostic features of aortic stenosis. We analyzed the association between 18F-FDG-PET/CT uptake pattern and degree of left ventricular mass index, aortic root dilatation, and aortic leaflet calcification extent. This is the first study to demonstrate that pre-discharge 18F-FDG-PET/CT in patients undergoing TAVR shows a significant negative correlation between 18F-FDG uptake pattern and adverse prognostic features.

Diagnostic Performance of Positron Emission Tomography with Fibroblast-Activating Protein Inhibitors in Gastric Cancer: A Systematic Review and Meta-Analysis.

Various papers have introduced the use of positron emission tomography (PET) with [68Ga]Ga-radiolabeled fibroblast-activation protein inhibitor (FAPi) radiopharmaceuticals in different subtypes of gastric cancer (GC). Our aim was to assess the diagnostic performance of this novel molecular imaging technique in GC with a systematic review and meta-analysis. A straightforward literature search of papers concerning the diagnostic performance of FAP-targeted PET imaging was performed. Original articles evaluating this novel molecular imaging examination in both newly diagnosed GC patients and GC patients with disease relapse were included. The systematic review included nine original studies, and eight of them were also eligible for meta-analysis. The quantitative synthesis provided pooled detection rates of 95% and 97% for the assessment of primary tumor and distant metastases, respectively, and a pooled sensitivity and specificity of 74% and 89%, respectively, for regional lymph node metastases. Significant statistical heterogeneity among the included studies was found only in the analysis of the primary tumor detection rate (I2 = 64%). Conclusions: Beyond the limitations of this systematic review and meta-analysis (i.e., all the included studies were conducted in Asia, and using [18F]FDG PET/CT as a comparator of the index test), the quantitative data provided demonstrate the promising diagnostic performance of FAP-targeted PET imaging in GC. Nevertheless, more prospective multicentric studies are needed to confirm the excellent performances of FAP-targeted PET in this cluster of patients.

[18F]FDG PET/MRI in children suffering from lymphoma: does MRI contrast media make a difference?

OBJECTIVES: Evaluate the influence of an MRI contrast agent application on primary and follow-up staging in pediatric patients with newly diagnosed lymphoma using [18F]FDG PET/MRI to avoid adverse effects and save time and costs during examination. METHODS: A total of 105 [18F]FDG PET/MRI datasets were included for data evaluation. Two different reading protocols were analyzed by two experienced readers in consensus, including for PET/MRI-1 reading protocol unenhanced T2w and/or T1w imaging, diffusion-weighted imaging (DWI), and [18F]FDG PET imaging and for PET/MRI-2 reading protocol an additional T1w post contrast imaging. Patient-based and region-based evaluation according to the revised International Pediatric Non-Hodgkin's Lymphoma (NHL) Staging System (IPNHLSS) was performed, and a modified standard of reference was applied comprising histopathology and previous and follow-up cross-sectional imaging. Differences in staging accuracy were assessed using the Wilcoxon and McNemar tests. RESULTS: In patient-based analysis, PET/MRI-1 and PET/MRI-2 both determined a correct IPNHLSS tumor stage in 90/105 (86%) exams. Region-based analysis correctly identified 119/127 (94%) lymphoma-affected regions. Sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy for PET/MRI-1 and PET/MRI-2 were 94%, 97%, 90%, 99%, 97%, respectively. There were no significant differences between PET/MRI-1 and PET/MRI-2. CONCLUSIONS: The use of MRI contrast agents in [18F]FDG PET/MRI examinations has no beneficial effect in primary and follow-up staging of pediatric lymphoma patients. Therefore, switching to a contrast agent-free [18F]FDG PET/MRI protocol should be considered in all pediatric lymphoma patients. CLINICAL RELEVANCE STATEMENT: This study gives a scientific baseline switching to a contrast agent-free [18F]FDG PET/MRI staging in pediatric lymphoma patients. This could avoid side effects of contrast agents and saves time and costs by a faster staging protocol for pediatric patients. KEY POINTS: • No additional diagnostic benefit of MRI contrast agents at [18F]FDG PET/MRI examinations of pediatric lymphoma primary and follow-up staging • Highly accurate primary and follow-up staging of pediatric lymphoma patients at MRI contrast-free [18F]FDG PET/MRI.

A Single High Dose of Flufenamic Acid in Rats does not Reduce the Damage Associated with the Rat Lithium-Pilocarpine Model of Status Epilepticus but Leads to Deleterious Outcomes.

BACKGROUND: Epilepsy is one of the most common neurologic diseases, and around 30% of all epilepsies, particularly the temporal lobe epilepsy (TLE), are highly refractory to current pharmacological treatments. Abnormal synchronic neuronal activity, brain glucose metabolism alterations, neurodegeneration and neuroinflammation are features of epilepsy. Further, neuroinflammation has been shown to contribute to dysregulation of neuronal excitability and the progression of epileptogenesis. Flufenamic acid (FLU), a non-steroidal anti-inflammatory drug, is also characterized by its wide properties as a dose-dependent ion channel modulator. In this context, in vitro studies have shown that it abolishes seizure-like events in neocortical slices stimulated with a gamma-aminobutyric acid A (GABAA) receptor blocker. However, little is known about its effects in animal models. Thus, our goal was to assess the efficacy and safety of a relatively high dose of FLU in the lithium-pilocarpine rat model of status epilepticus (SE). This animal model reproduces many behavioral and neurobiological features of TLE such as short-term brain hypometabolism, severe hippocampal neurodegeneration and inflammation reflected by a marked reactive astrogliosis. METHODS: FLU (100 mg/kg, i.p.) was administered to adult male rats, 150 min before SE induced by pilocarpine. Three days after the SE, brain glucose metabolism was assessed by 2-deoxy-2-[18F]-fluoro-D-glucose ([18F]FDG) positron emission tomography (PET). Markers of hippocampal integrity, neurodegeneration and reactive astrogliosis were also evaluated. RESULTS: FLU neither prevented the occurrence of the SE nor affected brain glucose hypometabolism as assessed by [18F]FDG PET. Regarding the neurohistochemical studies, FLU neither prevented neuronal damage nor hippocampal reactive astrogliosis. On the contrary, FLU increased the mortality rate and negatively affected body weight in the rats that survived the SE. CONCLUSIONS: Our results do not support an acute anticonvulsant effect of a single dose of FLU. Besides, FLU did not show short-term neuroprotective or anti-inflammatory effects in the rat lithium-pilocarpine model of SE. Moreover, at the dose administered, FLU resulted in deleterious effects.

Multimodality radiomics analysis based on [18F]FDG PET/CT imaging and multisequence MRI: application to nasopharyngeal carcinoma prognosis.

OBJECTIVES: To determine whether radiomics models developed from 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) PET/CT combined with multisequence MRI could contribute to predicting the progression-free survival (PFS) of nasopharyngeal carcinoma (NPC) patients. METHODS: One hundred thirty-two NPC patients who underwent both PET/CT and MRI scanning were retrospectively enrolled (88 vs. 44 for training vs. testing). For each modality/sequence (i.e., PET, CT, T1, T1C, and T2), 1906 radiomics features were extracted from the primary tumor volume. Univariate Cox model and correlation analysis were used for feature selection. A multivariate Cox model was used to establish radiomics signature. Prognostic performances of 5 individual modality models and 12 multimodality models (3 integrations × 4 fusion strategies) were assessed by the concordance index (C-index) and log-rank test. A clinical-radiomics nomogram was built to explore the clinical utilities of radiomics signature, which was evaluated by discrimination, calibration curve, and decision curve analysis (DCA). RESULTS: The radiomics signatures of individual modalities showed limited prognostic efficacy with a C-index of 0.539-0.664 in the testing cohort. Different fusion strategies exhibited a slight difference in predictive performance. The PET/CT and MRI integrated model achieved the best performance with a C-index of 0.745 (95% CI, 0.619-0.865) in the testing cohort (log-rank test, p < 0.05). Clinical-radiomics nomogram further improved the prognosis, which also showed satisfactory discrimination, calibration, and net benefit. CONCLUSIONS: Multimodality radiomics analysis by combining PET/CT with multisequence MRI could potentially improve the efficacy of PFS prediction for NPC patients. KEY POINTS: • Individual modality radiomics models showed limited performance in prognosis evaluation for NPC patients. • Combined PET, CT and multisequence MRI radiomics signature could improve the prognostic efficacy. • Multilevel fusion strategies exhibit comparable performance but feature-level fusion deserves more attention.

Meta-analysis assessing the sensitivity and specificity of 18F-FDG PET/CT for the diagnosis of prosthetic valve endocarditis (PVE) using individual patient data (IPD).

IMPORTANCE: The use of 18F-FDG PET/CT in diagnostic algorithms for PVE has increased since publication of studies and guidelines advocating its use. The assessment of test accuracy has been limited by small study sizes. We undertook a systematic review using individual patient data (IPD) meta-analysis techniques. OBJECTIVE: To estimate the summary sensitivity and specificity of 18F-FDG PET/CT in diagnosing PVE. We also assessed the effect of patient factors on test accuracy as defined by changes in the odds ratios associated with each factor. The effect of the PET/CT study on the final diagnosis was also assessed when compared to the preliminary Duke classification to determine in which patient group 18F-FDG PET/CT had the greatest utility. STUDY SELECTION: Studies were included if PET/CT was performed for suspicion of PVE and IPD of both the PET/CT result and final diagnosis defined by a gold-standard assessment was available. There were 3 possible final diagnoses ("definite PVE," "possible PVE," and "rejected PVE"). RESULTS: Seventeen studies were included with IPD available for 537 patients (from 538 scans). The summary sensitivity and specificity were 85% (95% CI 74.2%-91.8%) and 86.5% (95% CI 75.8%-92.9%) respectively when patients with final diagnosis of "possible PVE" were classified as positive for PVE. When this group was classified as negative for PVE, sensitivity was 87.4% (95% CI 80.4%-92.1%) and specificity was 84.9% (95% CI 71.5%-92.6%). Patients with a known pathogen (especially coagulase negative staphylococcal species), elevated CRP, a biological or aortic valve infection appeared more likely to have an accurate PET/CT diagnosis. Those with a mechanical valve, prior antibiotic treatment or a transcatheter aortic valve replacement valve were less likely to have an accurate test. Time since valve implantation and the presence of surgical adhesive did not appear to affect test accuracy. Of the patients with a preliminary Duke classification of "possible PVE," 84% received a more conclusive final diagnosis of "definite" or "rejected" PVE after the PET/CT study. CONCLUSIONS AND RELEVANCE: 18F-FDG PET/CT has high sensitivity and specificity in diagnosing PVE and the diagnostic utility is greatest in patients with a preliminary Duke classification of "possible PVE." Some patient factors appear to affect test accuracy, though these results should be interpreted with caution given low patient numbers for subgroup analyses.

Development and validation of a [18F]FDG PET/CT-based radiomics nomogram to predict the prognostic risk of pretreatment diffuse large B cell lymphoma patients.

OBJECTIVE: In this study, based on PET/CT radiomics features, we developed and validated a nomogram to predict progression-free survival (PFS) for cases with diffuse large B cell lymphoma (DLBCL) treated with immunochemotherapy. METHODS: This study retrospectively recruited 129 cases with DLBCL. Among them, PET/CT scans were conducted and baseline images were collected for radiomics features along with their clinicopathological features. Radiomics features related to recurrence were screened for survival analysis using univariate Cox regression analysis with p < 0.05. Next, a weighted Radiomics-score (Rad-score) was generated and independent risk factors were obtained from univariate and multivariate Cox regressions to build the nomogram. Furthermore, the nomogram was tested for their ability to predict PFS using time-dependent receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA). RESULTS: Blood platelet, Rad-score, and gender were included in the nomogram as independent DLBCL risk factors for PFS. We found that the training cohort areas under the curve (AUCs) were 0.79, 0.84, and 0.88, and validation cohort AUCs were 0.67, 0.83, and 0.72, respectively. Further, the DCA and calibration curves confirmed the predictive nomogram's clinical relevance. CONCLUSION: Using Rad-score, blood platelet, and gender of the DLBCL patients, a PET/CT radiomics-based nomogram was developed to guide cases' recurrence risk assessment prior to treatment. The developed nomogram can help provide more appropriate treatment plans to the cases. KEY POINTS: • DLBCL cases can be classified into low- and high-risk groups using PET/CT radiomics based Rad-score. • When combined with other clinical characteristics (gender and blood platelet count), Rad-score can be used to predict the outcome of the pretreatment of DLBCL cases with a certain degree of accuracy. • A prognostic nomogram was established in this study in order to aid in assessing prognostic risk and providing more accurate treatment plans for DLBCL cases.

18 F-FDG PET/CT imaging for haemophilic arthropathy compared with clinical, radiological and power Doppler sonographic characteristics of 20 haemophilia patients.

INTRODUCTION AND OBJECTIVES: Repeated joint bleeding in haemophilia patients may lead to haemophilic arthropathy with marked inflammation and synovitis. This study investigated the potential of 18 F-fluorodeoxyglucose positron emission tomography-computed tomography (18 F-FDG PET/CT) as a novel diagnostic method for haemophilic arthropathy. MATERIALS AND METHODS: We recruited 20 adult haemophilia patients who reported history of hemarthroses in the shoulder, elbow, hip, knee, or ankle joints. All joints were assessed by power Doppler ultrasonography and radiography, and graded by hyperaemia score and Pettersson score, respectively. Joint pain was evaluated by visual analogue score (VAS). Range of motion (ROM), Haemophilia Joint Health Score (HJHS) and annual joint bleeding rate (AJBR) were recorded. Finally, all participants had whole-body 18 F-FDG PET/CT, and maximum standardized uptake value (SUVmax) of the joints being studied was measured. RESULTS: Thirteen patients had severe haemophilia, and seven had moderate haemophilia. The mean age was 36 years. PET SUVmax showed significant correlations with VAS, ROM, Pettersson score, hyperaemia score, HJHS score and AJBR in all large joints except hip. Joints with pain, hyperaemia and radiographic changes were found to have higher SUVmax than those without these features. Using Youden's index, the optimal cut-off value for early radiographical arthropathy was found to be between 1.9 and 2.0. CONCLUSION: Our study indicates that 18 F-FDG PET/CT imaging correlated well with various conventional diagnostic techniques. It also demonstrated high sensitivity and specificity for early radiographic arthropathy. 18 F-FDG PET/CT imaging may quantitatively evaluate disease activity of most large joints in a single examination and help detect early haemophilic arthropathy.

Brown adipose tissue and regulation of human body weight.

BACKGROUND: Approximately 30% of the global population is affected by obesity. Traditional non-surgical measures for weight loss have limited efficacy and tolerability. Therefore, there is a need for novel, effective therapies. Brown adipose tissue (BAT) has been implicated in physiological energy expenditure, indicating that it could be targeted to achieve weight loss in humans. The use of 18 F-fluorodeoxyglucose (18 F-FDG) positron emission tomography-computed tomography-(PET-CT) imaging has enabled the discovery of functionally active BAT in the supraclavicular, subclavian, and thoracic spine regions of human adults. This review aims to discuss the reasons behind the renewed interest in BAT, assess whether it is metabolically important in humans, and evaluate its feasibility as a therapeutic target for treating obesity. SOURCES OF MATERIAL: PubMed Central, Europe PMC, Medline. FINDINGS: In vivo studies have shown that BAT activity is regulated by thyroid hormones and the sympathetic nervous system. Furthermore, BAT uniquely contains uncoupling protein 1 (UCP1) that is largely responsible for non-shivering thermogenesis. Cold exposure can increase BAT recruitment through the browning of white adipose tissue (WAT); however, this technique has practical limitations that may preclude its use. Currently available medicines for humans, such as the ß3-adrenergic receptor agonist mirabegron or the farnesoid X receptor agonist obeticholic acid, have generated excitement, although adverse effects are a concern. Capsinoids represent a tolerable alternative, which require further investigation. CONCLUSIONS: The use of currently available BAT-activating agents alone is unlikely to achieve significant weight loss in humans. A combination of BAT activation with physical exercise and modern, successful dietary strategies represents a more realistic option.

Glycolytic potential enhanced by blockade of pyruvate influx into mitochondria sensitizes prostate cancer to detection and radiotherapy.

OBJECTIVE: This study aimed to evaluate the effects of mitochondrial pyruvate carrier (MPC) blockade on the sensitivity of detection and radiotherapy of prostate cancer (PCa). METHODS: We investigated glycolysis reprogramming and MPC changes in patients with PCa by using metabolic profiling, RNA-Seq, and tissue microarrays. Transient blockade of pyruvate influx into mitochondria was observed in cellular studies to detect its different effects on prostate carcinoma cells and benign prostate cells. Xenograft mouse models were injected with an MPC inhibitor to evaluate the sensitivity of 18F-fluorodeoxyglucose positron emission tomography with computed tomography and radiotherapy of PCa. Furthermore, the molecular mechanism of this different effect of transient blockage towards benign prostate cells and prostate cancer cells was studied in vitro. RESULTS: MPC was elevated in PCa tissue compared with benign prostate tissue, but decreased during cancer progression. The transient blockade increased PCa cell proliferation while decreasing benign prostate cell proliferation, thus increasing the sensitivity of PCa cells to 18F-PET/CT (SUVavg, P = 0.016; SUVmax, P = 0.03) and radiotherapy (P < 0.01). This differential effect of MPC on PCa and benign prostate cells was dependent on regulation by a VDAC1-MPC-mitochondrial homeostasis-glycolysis pathway. CONCLUSIONS: Blockade of pyruvate influx into mitochondria increased glycolysis levels in PCa but not in non-carcinoma prostate tissue. This transient blockage sensitized PCa to both detection and radiotherapy, thus indicating that glycolytic potential is a novel mechanism underlying PCa progression. The change in the mitochondrial pyruvate influx caused by transient MPC blockade provides a critical target for PCa diagnosis and treatment.

Use of deep learning-based radiomics to differentiate Parkinson's disease patients from normal controls: a study based on [18F]FDG PET imaging.

OBJECTIVES: We proposed a novel deep learning-based radiomics (DLR) model to diagnose Parkinson's disease (PD) based on [18F]fluorodeoxyglucose (FDG) PET images. METHODS: In this two-center study, 255 normal controls (NCs) and 103 PD patients were enrolled from Huashan Hospital, China; 26 NCs and 22 PD patients were enrolled as a separate test group from Wuxi 904 Hospital, China. The proposed DLR model consisted of a convolutional neural network-based feature encoder and a support vector machine (SVM) model-based classifier. The DLR model was trained and validated in the Huashan cohort and tested in the Wuxi cohort, and accuracy, sensitivity, specificity and receiver operator characteristic (ROC) curve graphs were used to describe the model's performance. Comparative experiments were performed based on four other models including the scale model, radiomics model, standard uptake value ratio (SUVR) model and DLR model. RESULTS: The DLR model demonstrated superiority in differentiating PD patients and NCs in comparison to other models, with an accuracy of 95.17% [90.35%, 98.13%] (95% confidence intervals, CI) in the Huashan cohort. Moreover, the DLR model also demonstrated greater performance in diagnosing PD early than routine methods, with an accuracy of 85.58% [78.60%, 91.57%] in the Huashan cohort. CONCLUSIONS: We developed a DLR model based on [18F]FDG PET images that showed good performance in the noninvasive, individualized prediction of PD and was superior to traditional handcrafted methods. This model has the potential to guide and facilitate clinical diagnosis and contribute to the development of precision treatment. KEY POINTS: The DLR method on [18F]FDG PET images helps clinicians to diagnose PD and PD subgroups from normal controls. A prospective two-center study showed that the DLR method provides greater diagnostic accuracy.

A new approach of statin therapy in carotid atherosclerosis: Targeting indices of plaque vulnerability on the top of lipid-lowering. A narrative review.

Novel imaging techniques and biomarkers have emerged as surrogate markers of carotid plaque vulnerability. In parallel, statin administration in patients with established carotid atherosclerosis not requiring revascularization has reduced the number of consequent cerebrovascular events. This reduction is not only attributed to the lipid-lowering properties of statins but also to their pleiotropic actions. The present literature review aimed to summarize the stabilizing effects of statins on carotid plaques based on imaging modalities and biomarkers and propose an alternative approach to their implementation. Moreover, we assessed the perioperative use of statins in patients undergoing carotid revascularization and the impact of aggressive vs. conventional statin therapy. Recent studies using: (1) ultrasound indices of plaque echogenicity; (2) fluorodeoxyglucose (FDG)-positron emission tomography (PET)/computed tomography (CT) scans for plaque inflammation assessment; or (3)magnetic resonance imaging (MRI) scans quantifying intraplaque hemorrhage, and lipid-rich necrotic core (LRNC) have shown quite promising results in evaluation of carotid plaque vulnerability. Based on those imaging modalities, a growing number of studies have demonstrated a very modest carotid plaque regression due to/induced by statins, while their stabilizing impact is disproportionally higher. Other studies assaying several biomarkers (e.g. inflammation, etc.) have confirmed a statin-induced carotid plaque stabilization. All the aforementioned benefits followed a dose-dependent pattern of statins, on top of the low-density lipoprotein cholesterol (LDL-C) target in current guidelines. In the case of symptomatic patients with carotid atherosclerosis suitable for revascularization, robust evidence implicates a significant statin-related reduction of perioperative cardiovascular risk only in patients undergoing endarterectomy.

Value of 18F-FDG pet/CT for prognostic assessment in patients with infective endocarditis.

BACKGROUND: 18F-FDG PET/CT is a valuable diagnostic tool in infective endocarditis (IE). However, the prognostic value is unclear. This study aims to evaluate the prognostic performance of 18F-FDG PET/CT in native valve endocarditis (NVE) and prosthetic valve endocarditis (PVE). METHODS: We retrospectively included 76 patients treated for definite IE (NVE and PVE) that underwent 18F-FDG PET/CT between January 2016 and December 2018. Clinical, echocardiographic and 18F-FDG PET/CT (pathologic valvular 18F-FDG uptake, extracardiac complications (ECC)) data were collected. The primary endpoint was defined as mortality or recurrence of IE at a one-year follow-up. RESULTS: Pathologic valvular 18F-FDG uptake was detected in 32 of 57 (56.1%) patients, 30% (9/30) in NVE and 85.2% (23/27) in PVE group. Atrial fibrillation (OR 3.90, 95% CI = 1.14-16.3), prior anticoagulation treatment (OR 6.37, 95% CI = 1.89-26.7), large vegetation (≥ 10 mm) (OR 4.05, 95% CI = 1.14-16.1), perivalvular complications (OR 7.22, 95% CI = 1.68-55.1) and abscess (OR 10.9, 95% CI = 1.84-283) were associated with positive PET/CT. Extracardiac complications were found in 27 of 76 (35.5%) patients, 42.9% (18/42) in the NVE and 26.5% (9/34) in the PVE group. Pathological valvular tracer uptake (HR 1.20, 95% CI = 0.43-3.37) or extracardiac complications (HR 0.58, 95% CI = 0.21-1.62) were not associated with the occurrence of the primary endpoint. CONCLUSION: Our study could not demonstrate a prognostic value of 18F-FDG PET/CT in IE, but confirms high diagnostic performance, which may compromise prognostic significance by accelerated optimal treatment because of earlier diagnostic certainty.