Microglia Density and Its Association With Disease Duration, Severity, and Orexin Levels in Patients With Narcolepsy Type 1.

BACKGROUND AND OBJECTIVES: Narcolepsy type 1 (NT1) is due to the loss of hypothalamic neurons that produce orexin (ORX), by a suspected immune-mediated process. Rare postmortem studies are available and failed to detect any inflammation in the hypothalamic region, but these brains were collected years after the first symptoms. In vivo studies close to disease onset are lacking. We aimed to explore microglia density in the hypothalamus and thalamus in NT1 compared with controls using [18F]DPA-714 PET and to study in NT1 the relationships between microglia density in the hypothalamus and in other regions of interest (ROIs) with disease duration, severity, and ORX levels. METHODS: Patients with NT1 and controls underwent a standardized clinical evaluation and [18F]DPA-714 PET imaging using a radiolabeled ligand specific to the 18 kDa translocator protein (TSPO). TSPO genotyping determined receptor affinity. Images were processed on peripheral module interface using standard uptake value (SUV) on ROIs: hypothalamus, thalamus, frontal area, cerebellum, and the whole brain. SUV ratios (SUVr) were calculated by normalizing SUV with cerebellum uptake. RESULTS: A total of 41 patients with NT1 (21 adults, 20 children, 10 with recent disease onset <1 year) and 35 controls were included, with no significant difference between groups for [18F]DPA-714 binding (SUV/SUVr) in the hypothalamus and thalamus. Unexpectedly, significantly lower SUVr in the whole brain was found in NT1 compared with controls (0.97 ± 0.06 vs 1.08 ± 0.22, p = 0.04). The same finding between NT1 and controls in the whole brain was observed in those with high or mixed TSPO affinity (p = 0.03 and p = 0.04). Similar trend was observed in the frontal area in NT1 (0.96 ± 0.09 vs 1.09 ± 0.25, p = 0.05). In NT1, no association was found between SUVr in different ROIs and age, disease duration, severity, or ORX levels. DISCUSSION: We found no evidence of in vivo increased microglia density in NT1 compared with controls, even close to disease onset, and even unexpectedly a decrease in the whole brain of these patients. These findings do not support the presence of neuroinflammation in the destruction process of ORX neurons. TRIAL REGISTRATION INFORMATION: ClinicalTrials.org NCT03754348.

Long-Term Overall Survival After Selective Internal Radiation Therapy for Locally Advanced Hepatocellular Carcinomas: Updated Analysis of DOSISPHERE-01 Trial.

Interim analysis of the DOSISPHERE-01 study demonstrated a strong improvement in response and overall survival (OS) on using 90Y-loaded glass microspheres with personalized dosimetry compared with standard dosimetry in patients with nonoperable locally advanced hepatocellular carcinoma. This report sought to provide a long-term analysis of OS. Methods: In this phase II study (ClinicalTrials.gov identifier NCT02582034), treatment was randomly assigned (1:1) with the goal to deliver either at least 205 Gy (if possible >250-300 Gy) to the index lesion in the personalized dosimetry approach (PDA) or 120 ± 20 Gy to the treated volume in the standard dosimetry approach (SDA). The 3-mo response of the index lesion was the primary endpoint, with OS being one of the secondary endpoints. This report is a post hoc long-term analysis of OS. Results: Overall, 60 hepatocellular carcinoma patients with at least 1 lesion larger than 7 cm and more than 30% of hepatic reserve were randomized (intent-to-treat population: PDA, n = 31; SDA, n = 29), with 56 actually treated (modified intent-to-treat population: n = 28 in each arm). The median follow-up for long-term analysis was 65.8 mo (range, 2.1-73.1 mo). Median OS was 24.8 mo and 10.7 mo (hazard ratio [HR], 0.51; 95% CI, 0.29-0.9; P = 0.02) for PDA and SDA, respectively, in the modified intent-to-treat population. Median OS was 22.9 mo for patients with a tumor dose of at least 205 Gy, versus 10.3 mo for those with a tumor dose of less than 205 Gy (HR, 0.42; 95% CI, 0.22-0.81; P = 0.0095), and was 22.9 mo for patients with a perfused liver dose of 150 Gy or higher, versus 10.3 mo for those with a perfused liver dose of less than 150 Gy (HR, 0.42; 95% CI, 0.23-0.75; P = 0.0033). Lastly, median OS was not reached in patients who were secondarily resected (n = 11, 10 in the PDA group and 1 in the SDA group), versus 10.8 mo in those without secondary resection (n = 45) (HR, 0.17; 95% CI, 0.065-0.43; P = 0.0002). Only resected patients displayed favorable long-term OS rates, meaning an OS of more than 50% at 5 y. Conclusion: After longer follow-up, personalized dosimetry sustained a meaningful improvement in OS, which was dramatically improved for patients who were accurately downstaged toward resection, including most portal vein thrombosis patients.

Cross-Calibration Study of The Stratos And Hologic QDR 4500A Dual-Energy X-Ray Absorptiometers to Assess Bone Mineral Density And Body Composition.

The objective of the study was to assess the agreement between the Stratos (DMS) and QDR 4500A (Hologic) DXAs in determining whole body and regional aBMD, as well as whole body composition. Fifty-five individuals (46 women: 84%) with a mean age of 41 ± 13.0 years (range: 20 to 64) and a mean BMI of 31.9 ± 10 kg/m² (range: 12.2 to 49.5) were consecutively scanned on the same day using the two devices. Predictive equations for areal bone mineral density (aBMD) and whole body composition (WBC) were derived from linear regression of the data. The two DXAs were highly correlated (p<0.001 for all parameters) with a correlation coefficient (r) ranging from 0.89 to 0.99 for aBMD (r=0.89 for whole body, r=0.92 for radius, r=0.95 for femoral neck, r=0.96 for total hip, and r=0.99 for L1-L4). For WBC, the r value was 0.98 for lean tissue mass (LTM) and 1.0 for fat mass (FM). Paired t-tests indicated a statistically significant bias between the two DXAs for the majority of measurements, requiring the determination of specific cross-calibration equations. Compared to QDR 4500A, Stratos underestimated whole body aBMD and LTM and overestimated neck and hip aBMD and whole body FM. Conversely, no significant bias was demonstrated for mean aBMD at L1-L4 and radius. For whole body aBMD and FM, the concordance between the two DXAs was influenced by BMI. Despite a high concordance between the two DXAs, the systematic bias for aBMD and WBC measurements illustrates the need to define cross-calibration equations to compare data across systems.

Relationship between Lean Tissue Mass and Muscle Function in Women with Obesity.

It is well documented that lean tissue mass (LTM) decreases with aging in patients with obesity, but there is no information available regarding muscle strength changes, a parameter that may be better associated with sarcopenic obesity (SO). The objectives of this study were to analyze the changes in LTM and fat mass (FM), muscle strength and muscle function with aging in women with obesity and to determine the prevalence of SO. LTM and FM were determined by DXA, muscle strength with the hand-grip test and muscle function with the 6 min walk test (6MWT) in 383 women with obesity. A redistribution of the LTM and FM occurred with age, characterized by a gain at the trunk to the detriment of the lower limbs, thus reducting in appendicular LTM indices. The physical performances evaluated by the muscle strength and muscle function decreased concomitantly, and the prevalence of low values for both these parameters was 22.8% and 13.4%, respectively, in the older patients. In summary, although a reduction in appendicular LTM and muscle performances occurred with age and resulted in an increase in the prevalence of SO, the number of women with obesity affected by SO remained low (n ≤ 15), even in those older than 60 years.

Whole-body vibration may not affect bone mineral density and bone turnover in persons with chronic spinal cord injury: A preliminary study.

CONTEXT: Spinal-cord injury (SCI) induces bone loss and dramatically increases the risk of fracture. OBJECTIVES: Determine the effects of whole-body vibration (WBV) on areal bone mineral density (aBMD), whole body composition and bone biological parameters in individuals with chronic-state SCI. DESIGN: Randomized study. SETTING: Centre Neurologique PROPARA. PARTICIPANTS: Fourteen subjects were randomly assigned to a WBV or a control group. INTERVENTIONS: WBV (20-45 min, 30-45 Hz, 0.5 g) was performed in verticalized persons twice weekly for 6 months. OUTCOME MEASURES: aBMD was measured by DXA at baseline and 6 months and bone biological parameters at baseline, 1, 3 and 6 months. RESULTS: No significant aBMD change was found in either the WBV or control group after 6 months of follow-up. Similarly, periostin, sclerostin and bone turnover markers remained relatively stable throughout follow-up and no difference in variation was observed within-group and between groups. Except for whole-body fat mass, which showed a significant decrease in the WBV group compared to controls, no difference in changes was observed, whatever the localization for fat and lean body mass. CONCLUSIONS: During the chronic phase, aBMD and bone remodeling reach a new steady state. However, the DXA technique and the bone markers, including sclerostin and periostin, both of which reflect bone cell activity influenced by mechanical strain, showed that the bone tissue of individuals with SCI was insensitive to 6 months of WBV training at the study dose. Nevertheless, results of this preliminary study that was underpowered need to be confirmed and other modalities of WBV may be more effective in improving aBMD of this population. TRIALS REGISTRATION: N°IDRCB:2011-A00224-37.

Effect of Nutritional Deprivation after Sleeve Gastrectomy on Bone Mass, Periostin, Sclerostin and Semaphorin 4D: A Two-Year Longitudinal Study.

Bariatric surgery induces bone loss, but the exact mechanisms by which this process occurs are not fully known. The aims of this 2-year longitudinal study were to (i) investigate the changes in areal bone mineral density (aBMD) and bone turnover markers following sleeve gastrectomy (SG) and (ii) determine the parameters associated with the aBMD variations. Bone turnover markers, sclerostin, periostin and semaphorin 4D were assessed before and 1, 12 and 24 months after SG, and aBMD was determined by DXA at baseline and after 12 and 24 months in 83 patients with obesity. Bone turnover increased from 1 month, peaked at 12 months and remained elevated at 24 months. Periostin and sclerostin presented only modest increases at 1 month, whereas semaphorin 4D showed increases only at 12 and 24 months. A significant aBMD decrease was observed only at total hip regions at 12 and 24 months. This demineralisation was mainly related to body weight loss. In summary, reduced aBMD was observed after SG in the hip region (mechanical-loading bone sites) due to an increase in bone turnover in favour of bone resorption. Periostin, sclerostin and semaphorin 4D levels varied after SG, showing different time lags, but contrary to weight loss, these biological parameters did not seem to be directly implicated in the skeletal deterioration.

Evaluation of 18-FDG PET diagnostic capabilities for cancer screening in heart transplant patients, a retrospective study.

Evaluate 18-FDG positron emission tomography (PET) diagnostic capabilities for cancer screening in heart transplant patients. We conducted an anonymized retrospective observational study of heart transplant patients followed in the University Hospital of Montpellier, France. We analyzed 303 18-FDG PET from 158 patients. We compared demographic and clinical characteristics through uni- and multivariate analysis: in the cancer-free group, comparisons were made between the PET false positive (FP) group versus true negative (TN), and in the cancer group, comparisons were made between the PET false negative (FN) group versus true positive (TP). Out of the 303 exams, we found 245 TN, 26 TP, 26 FP and 6 FN. The sensitivity rate was calculated at 81%, the specificity rate at 90%, the positive predictive value at 50%, and the negative predictive value at 97%. The multivariate analysis showed an association between FP diagnosis and graft-PET delay (P value = .046, OR = 5.14, 95% CI [1.18-32.4]) and creatine reactive protein (CRP) ≥ 10 mg/L (P value = .042, OR = 4.21, 95% CI [1.02-17.2]). The estimated probability of FP by logit regression was 0.48 with 95% CI [0.21-0.77] when graft-PET delay ≥ 6 years and CRP ≥ 10 mg/L. No significative statistical link was found for the demographic or clinical characteristics in the FN group of patients with cancer, except for sex (all FN were men). 18-FDG PET performed very well in the follow-up of heart transplant patients for neoplasia screening, with better specificity than sensitivity. However, the study showed that almost 50% of FP can be predicted by considering only the graft-PET delay and CRP.

Functional PET Neuroimaging in Consciousness Evaluation: Study Protocol.

Ensuring a robust and reliable evaluation of coma deepness and prognostication of neurological outcome is challenging. We propose to develop PET neuroimaging as a new diagnostic and prognosis tool for comatose patients using a recently published methodology to perform functional PET (fPET). This exam permits the quantification of task-specific changes in neuronal metabolism in a single session. The aim of this protocol is to determine whether task-specific changes in glucose metabolism during the acute phase of coma are able to predict recovery at 18 months. Participation will be proposed for all patients coming for a standard PET-CT in our center in order to evaluate global cerebral metabolism during the comatose state. Legally appointed representative consent will be obtained to slightly modify the exam protocol: (1) 18F-fluorodeoxyglucose (18F-FDG) bolus plus continuous infusion instead of a simple bolus and (2) more time under camera to perform dynamic acquisition. Participants will undergo a 55-min fPET session with a 20% bolus + 80% infusion protocol. Two occurrences of three block (5-min rest, 10-min auditory stimulation and 10-min emotional auditory stimulation) will be performed after reaching equilibrium of FDG arterial concentration. We will compare the regional brain metabolism at rest and during the sessions of auditory and emotional auditory stimulation to search for a determinant of coma recovery (18 months of follow-up after the exam). Emotional auditory stimulation should induce an activation of: the auditory cortex, the consciousness areas and the neural circuitry for emotion (function to coma deepness). An activation analysis will be carried out to highlight regional brain activation using dedicated custom-made software based on Python statistical and image processing toolboxes. The association between activation levels and the Coma Recovery Scale-Revisited (CRS-R) will be assessed using multivariate analysis. If successful, the results from this study will help improve coma prognosis evaluation based on the pattern of neuronal metabolism at the onset of the pathology. The study protocol, rationale and methods are described in this paper.

Large, multifocal or portal vein-invading hepatocellular carcinoma (HCC) downstaged by Y90 using personalized dosimetry: safety, pathological results and outcomes after surgery.

Background: Transarterial radioembolization (TARE) has recently been recognized as a bridging/downstaging therapy to surgery for early hepatocellular carcinomas (HCCs) with high rates of complete pathological necrosis (CPN) on liver explants. In patients with portal vein tumoral thrombus (PVTT), multifocal or large tumors, TARE has mainly a palliative role and surgery remains controversial in this poor-prognosis population. Personalized dosimetry recently proved to outperform standard dosimetry used in prior negative Y90 randomized-controlled trials. Methods: In this retrospective study, we evaluated safety, radiological and pathological response and outcomes in HCC patients with PVTT, multifocal or large tumors, who underwent surgery after downstaging using TARE with Y90-loaded glass microspheres with personalized dosimetry. Results: Between December 2015 and October 2021, 18 unresectable patients (14/18 with PVTT) had surgery (16 resections, 2 liver transplantations) 6.2 months (range, 2-14.6 months) after a single Y90 treatment. No 90-day mortality was reported. Objective modified response criteria in solid tumors (mRECIST) response were noted in all but one patient. Complete and extensive (50-99%) necrosis was observed in 36% and 45% of tumors, respectively. The post-treatment tumor-absorbed dose significantly differed depending on the extent of pathological necrosis (P=0.045). Median overall survival and progression-free survival (PFS) were respectively of 61.8 months [95% CI: 31.4 months-not reached (NR)] and 49.3 months (95% CI: 14 months-NR). PFS was longer in patients with complete imaging response [median NR (none recurred or died) vs. 21.5 months (95% CI: 10.1 months-NR), P<0.001] and in those with complete pathological response [median NR vs. 22.5 months (95% CI: 10.1 months-NR), P<0.001]. Conclusions: Y90 TARE using personalized dosimetry can provide high rates of imaging and pathological response in patients with PVTT, large or multifocal HCC. Subsequent surgery is safe and leads to outcomes far exceeding expectations in an otherwise poor prognosis population with no chance for cure. Trial Registration: Clinical trial number: NCT05045573.

Alteration of Volumetric Bone Mineral Density Parameters in Men with Spinal Cord Injury.

Spinal cord injury (SCI) induces severe losses of trabecular and cortical volumetric bone mineral density (vBMD), which cannot be discriminated with conventional dual-energy X-ray absorptiometry (DXA) analysis. The objectives were to: (i) determine the effects of SCI on areal BMD (aBMD) and vBMD determined by advanced 3D-DXA-based methods at various femoral regions and (ii) model the profiles of 3D-DXA-derived parameters with the time since injury. Eighty adult males with SCI and 25 age-matched able-bodied (AB) controls were enrolled in this study. Trabecular and cortical vBMD, cortical thickness and derived strength parameters were assessed by 3D-SHAPER® software at various femoral subregions. Individuals with SCI had significantly lower integral vBMD, trabecular vBMD, cortical vBMD, cortical thickness and derived bone strength parameters (p < 0.001 for all) in total proximal femur compared with AB controls. These alterations were approximately to the same degree for all three femoral subregions, and the difference between the two groups tended to be greater for cortical vBMD than trabecular vBMD. There were minor differences according to the lesion level (paraplegics vs tetraplegics) for all 3D-DXA-derived parameters. For total proximal femur, the decreasing bone parameters tended to reach a new steady state after 5.1 years for integral vBMD, 7.4 years for trabecular vBMD and 9.2 years for cortical vBMD following SCI. At proximal femur, lower vBMD (integral, cortical and trabecular) and cortical thickness resulted in low estimated bone strength in individuals with SCI. It remains to be demonstrated whether these new parameters are more closely associated with fragility fracture than aBMD.

Intraputaminal Gene Delivery in Two Patients with Aromatic L-Amino Acid Decarboxylase Deficiency.

Background: Aromatic l-amino acid decarboxylase deficiency (AADCD) is a rare, early-onset, dyskinetic encephalopathy mostly reflecting a defective synthesis of brain dopamine and serotonin. Intracerebral gene delivery (GD) provided a significant improvement among AADCD patients (mean age, ≤6 years). Objective: We describe the clinical, biological, and imaging evolution of two AADCD patients ages >10 years after GD. Methods: Eladocagene exuparvovec, a recombinant adeno-associated virus containing the human complimentary DNA encoding the AADC enzyme, was administered into bilateral putamen by stereotactic surgery. Results: Eighteen months after GD, patients showed improvement in motor, cognitive and behavioral function, and in quality of life. Cerebral l-6-[18F] fluoro-3, 4-dihydroxyphenylalanine uptake was increased at 1 month, persisting at 1 year compared to baseline. Conclusion: Two patients with a severe form of AADCD had an objective motor and non-motor benefit from eladocagene exuparvovec injection even when treated after the age of 10 years, as in the seminal study.

Changes in Lean Tissue Mass, Fat Mass, Biological Parameters and Resting Energy Expenditure over 24 Months Following Sleeve Gastrectomy.

Sleeve gastrectomy (SG) induces weight loss but its effects on body composition (BC) are less well known. The aims of this longitudinal study were to analyse the BC changes from the acute phase up to weight stabilization following SG. Variations in the biological parameters related to glucose, lipids, inflammation, and resting energy expenditure (REE) were concomitantly analysed. Fat mass (FM), lean tissue mass (LTM), and visceral adipose tissue (VAT) were determined by dual-energy X-ray absorptiometry in 83 obese patients (75.9% women) before SG and 1, 12 and 24 months later. After 1 month, LTM and FM losses were comparable, whereas at 12 months the loss of FM exceeded that of LTM. Over this period, VAT also decreased significantly, biological parameters became normalized, and REE was reduced. For most of the BC, biological and metabolic parameters, no substantial variation was demonstrated beyond 12 months. In summary, SG induced a modification in BC changes during the first 12 months following SG. Although the significant LTM loss was not associated with an increase in sarcopenia prevalence, the preservation of LTM might have limited the reduction in REE, which is a longer-term weight-regain criterion.

Measuring myocardial blood flow using dynamic myocardial perfusion SPECT: artifacts and pitfalls.

Dynamic acquisition allows absolute quantification of myocardial perfusion and flow reserve, offering an alternative to overcome the potential limits of relative quantification, especially in patients with balanced multivessel coronary artery disease. SPECT myocardial perfusion is widely available, at lower cost than PET. Dynamic cardiac SPECT is now feasible and has the potential to be the next step of comprehensive perfusion imaging. In order to help nuclear cardiologists potentially interested in using dynamic perfusion SPECT, we sought to review the different steps of acquisition, processing, and reporting of dynamic SPECT studies in order to enlighten the potentially critical pitfalls and artifacts. Both patient-related and technical artifacts are discussed. Key parameters of the acquisition include pharmacological stress, radiopharmaceuticals, and injection device. When it comes to image processing, attention must be paid to image-derived input function, patient motion, and extra-cardiac activity. This review also mentions compartment models, cameras, and attenuation correction. Finally, published data enlighten some facets of dynamic cardiac SPECT while several issues remain. Harmonizing acquisition and quality control procedures will likely improve its performance and clinical strength.

Definition of an adapted cut-off for determining low lean tissue mass in older women with obesity: a comparison to current cut-offs.

The prevalence of sarcopenia in patients with obesity varies according to the definition used. The purpose of our study was to: (i) determine the prevalence of sarcopenia in terms of lean tissue mass in older women with obesity using the current cut-offs, (ii) redefine a specific cut-off for low lean tissue mass (LLTM), and (iii) re-determine the prevalence of LLTM using this new cut-off. Appendicular lean mass (ALM) and the ALM index [ALM/height2: ALMI(h2)] and ALMI/body mass index [ALMI(BMI)] were determined in 791 women with or without obesity. LLMM prevalence was calculated using the current cut-offs: EWGSOP2: ALM < 15 kg and ALMI(h2) < 5.5 kg/m2; FNIH: ALM < 15.02 kg and ALMI(BMI) < 0.51; and IWGS: ALMI(h2) < 5.67 kg/m2 and cut-offs newly determined from data provided from young women with obesity. ALM, ALMI(h2) and ALMI(BMI) were lower in older compared to young obese women. Using the current cut-offs, a wide distribution of LLTM prevalence (0 to 29.2%) was observed. When the newly determined cut-offs were applied - i.e., ALM < 18.51 kg; ALMI(h2) < 7.15 kg/m2, ALMI(BMI) < 0.483, and T-score: [(ALMI(h2) measured)-(2.08 + 0.183*BMI)]/0.72] - the LLTM mass prevalence was 17.37%; 8.47, 14.8 and 12.71%. respectively. This study showed that the current cut-offs for LLTM as criteria for sarcopenia diagnosis are not adapted to the obese population. Although the new "static" cut-offs appeared to be more adapted, a "dynamic" cut-off for ALMI(h2) that took into account the BMI and thus the obesity severity appeared even more relevant.

Comparison of the Lunar Prodigy and Stratos DR Dual-Energy X-Ray Absorptiometers to Assess Regional Bone Mineral Density.

PURPOSE: The first objective of the study was to assess the agreement between the Stratos DR (DMS) and the GE Prodigy (GE) DXAs in determining femoral neck, total hip and lumbar spine aBMD. The second objective was to assess the potential impact of leg positioning (hip flexed at 90° or not) on lumbar spine aBMD. METHODS: Forty-six individuals (n=42 women, 91.3%), with a mean age of 59.7 ± 13 years and mean BMI of 23.8 ± 4.7 kg/m², were scanned consecutively on the same day using the two devices. In a subgroup (n=30), two consecutive Stratos DR scans (with hip flexed at 90° or not) at the lumbar spine were conducted. Predictive equations for hip and lumbar spine aBMD were derived from linear regression of the data. RESULTS: Correlation coefficients for aBMD measured with the two DXAs were characterised by an R² of 0.76 for the femoral neck, 0.89 for the total hip, and 0.86 for the lumbar spine. However, the derived equations for aBMD determination showed an intercept significantly different from 0 for hip aBMD, and a slope significantly different from 1 for lumbar spine aBMD. These results highlight a bias between the two measurements, thus requiring the determination of specific cross-calibration equations for hip and lumbar spine, femoral neck excepted. When compared with values on the Prodigy, mean aBMD on the Stratos DR was higher at the femoral neck (+4.8%, p<0.001) and total hip (+9.6%, p<0.001) and lower at L2-L4 (-8.8%, p<0.001). The coefficient of variation (CV%) for the two consecutive measures at lumbar spine (with different positioning) with the Stratos DR was 2.9%. CONCLUSIONS: The difference in aBMD measured with the two DXAs illustrates the need to define cross-calibration equations when comparing data across systems in order to avoid erroneous conclusions.

Delayed [ 18 F]-FDG PET Imaging Increases Diagnostic Performance and Reproducibility to Differentiate Recurrence of Brain Metastases From Radionecrosis.

PURPOSE: Differentiating brain metastasis recurrence from radiation necrosis can be challenging during MRI follow-up after stereotactic radiotherapy. [ 18 F]-FDG is the most available PET tracer, but standard images performed 30 to 60 minutes postinjection provide insufficient accuracy. We compared the diagnostic performance and interobserver agreement of [ 18 F]-FDG PET with delayed images (4-5 hours postinjection) with the ones provided by standard and dual-time-point imaging. METHODS: Consecutive patients referred for brain [ 18 F]-FDG PET after inconclusive MRI were retrospectively included between 2015 and 2020 in 3 centers. Two independent nuclear medicine physicians interpreted standard (visually), delayed (visually), and dual-time-point (semiquantitatively) images, respectively. Adjudication was applied in case of discrepancy. The final diagnosis was confirmed histologically or after 6 months of MRI follow-up. Areas under the receiver operating characteristic curves were pairwise compared. RESULTS: Forty-eight lesions from 46 patients were analyzed. Primary tumors were mostly located in the lungs (57%) and breast (23%). The median delay between radiotherapy and PET was 15.7 months. The final diagnosis was tumor recurrence in 24 of 48 lesions (50%), with histological confirmation in 19 of 48 lesions (40%). Delayed images provided a larger area under the receiver operating characteristic curve (0.88; 95% confidence interval [CI], 0.75-0.95) than both standard (0.69; 95% CI, 0.54-0.81; P = 0.0014) and dual-time-point imaging (0.77; 95% CI, 0.63-0.88; P = 0.045), respectively. Interobserver agreement was almost perfect with delayed images ( κ = 0.83), whereas it was moderate with both standard ( κ = 0.48) and dual-time-point images ( κ = 0.61). CONCLUSIONS: [ 18 F]-FDG PET with delayed images is an accurate and reliable alternative to differentiate metastasis recurrence from radiation necrosis in case of inconclusive MRI after brain stereotactic radiotherapy.

In patients with anorexia nervosa, myokine levels are altered but are not associated with bone mineral density loss and bone turnover alteration.

Objectives: The two-fold aim of this study was: (i) to determine the effects of undernutrition on the myokines in patients with restrictive anorexia nervosa (AN) and (ii) to examine the potential link between myokines and bone parameters. Methods: In this study, 42 young women with restrictive AN and 42 age-matched controls (CON) (mean age, 18.5 ± 4.2 years and 18.6 ± 4.2 years, respectively) were enrolled. aBMD and body composition were determined with DXA. Resting energy expenditure (REEm), a marker of energy status, was indirectly assessed by calorimetry. Bone turnover markers and myokines (follistatin, myostatin and irisin) were concomitantly evaluated. Results: AN patients presented low aBMD at all bone sites. REEm, bone formation markers, myostatin and IGF-1 were significantly lower, whereas the bone resorption marker and follistatin were higher in AN compared with controls. No difference was observed between groups for irisin levels. When the whole population was studied, among myokines, only myostatin was positively correlated with aBMD at all bone sites. However, multiple regression analyses showed that in the AN group, the independent variables for aBMD were principally amenorrhoea duration, lean tissue mass (LTM) and procollagen type I N-terminal propeptide (PINP). For CON, the independent variables for aBMD were principally LTM, age and PINP. Whatever the group analysed, none of the myokines appeared as explicative independent variables of aBMD. Conclusion: This study demonstrated that despite the altered myokine levels in patients with AN, their direct effect on aBMD loss and bone turnover alteration seems limited in comparison with other well-known disease-related factors such as oestrogen deprivation.

Evaluating the Effectiveness of Yttrium-90 Glass Microspheres in the Treatment of Hepatocellular Carcinoma, Intrahepatic Cholangiocarcinoma, and Metastatic Colorectal Cancer in Practice: Protocol for the Prospective PROACTIF Phase IV Registry Study in France.

PRIMARY OBJECTIVE: Recently, selective internal radiation therapy using yttrium-90 (Y90) glass microspheres (TheraSphere™) was approved for reimbursement by health authorities in France. The PROACTIF study aims to gather data on effectiveness, patient quality of life, and safety with use of Y90 glass microspheres in real-world clinical settings in France. INCLUSION CRITERIA: Patient with a diagnosis of hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (iCC), and/or metastatic colorectal cancer (mCRC) who was treated with a dose of Y90 glass microspheres that has been reimbursed in France and who do not oppose use of their personal medical data. EXCLUSION CRITERIA: If data collection is opposed, treatment is reimbursed but not administered, or treatment is administered but not reimbursed. OUTCOME MEASURES: Primary outcome measures include overall survival from time of Y90 glass microsphere treatment and quality of life, as assessed using the Functional Assessment of Cancer Therapy- Hepatobiliary questionnaire. ESTIMATED NUMBER OF PATIENTS TO BE INCLUDED: This is an open study and there is no set number of patients; 115 have already been enrolled. PLANNED SUBGROUP ANALYSES: Analyses will be stratified by disease state (HCC, iCC, or mCRC). Subgroups to be analyzed include age group, unilobar/bilobar disease at baseline, Eastern Cooperative Oncology Group (ECOG) status at baseline, liver tumor burden at baseline, target lesion size, and standard versus multi-compartment personalized dosimetry treatment. PLANNED RECRUITMENT AND OBSERVATION PERIOD: Recruitment includes patients who are prescribed and treated with a commercial vial of Y90 glass microspheres between 01 January 2019 and 31 December 2024. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04069468.

Colchicine to Prevent Sympathetic Denervation after an Acute Myocardial Infarction: The COLD-MI Trial Protocol.

Inflammatory processes are deeply involved in ischemia-reperfusion injuries (IRI) and ventricular remodelling (VR) after a ST-segment elevation myocardial infarction (STEMI). They are associated with clinical adverse events (heart failure and cardiovascular death) adding damage to the myocardium after reperfusion. Moreover, acute myocardial infarction (AMI) induces a local sympathetic denervation leading to electrical instability and arrythmia. Colchicine, a well-known alkaloid with direct anti-inflammatory effects, was shown to reduce the myocardial necrosis size and limit the VR. In a recent proof of concept study, colchicine appears to prevent sympathetic denervation in a mice model of ischemia/reperfusion, but not in the necrosis or in the border zone areas. The Colchicine to Prevent Sympathetic Denervation after an AMI study (COLD-MI) is an ongoing, confirmative, prospective, monocentre, randomized, open-label trial. The COLD-MI trial aims to evaluate the intensity of sympathetic denervation after AMI and its potential modulation due to low dose colchicine. Sympathetic denervation will be noninvasively evaluated using single-photon emission computed tomography (SPECT). After a first episode of STEMI (Initial TIMI flow ≤ 1) and primary percutaneous coronary intervention (PPCI), patients will be randomized (n = 56) in a 1:1 ratio to either receive colchicine or not for 30 days. The primary end point will be the percentage of myocardial denervation measured by 123I-metaiodobenzylguanidine (123I-MIBG) SPECT at a 6-month follow-up. The main secondary end points will be basic ECG parameters (QRS duration, corrected QT) and HRV parameters from a 24 hour-recording Holter at 1- and 6-months follow-up. Results from this study will contribute to a better understanding of the cardioprotective effect of colchicine after AMI. The present study describes the rationale, design, and methods of the trial.