Comparison of plasma clearance of [51Cr]CrEDTA based on three, two and single samples to measure the glomerular filtration rate in patients with solid tumors: a prospective cross-sectional analysis.

OBJECTIVES: [51Cr]CrEDTA is used to measure the Glomerular Filtration Rate (GFR) in different clinical conditions. However, there is no consensus on the ideal number of blood samples to be taken and at what time points to measure its clearance. This study aimed to compare Slope Intercept (SI) and Single-Sample (SS) methods for measuring GFR in patients with solid tumors, stratified by age, GFR, and Body Mass Index (BMI). METHODS: 1,174 patients with cancer were enrolled in this prospective study. GFR was calculated by the SI method using blood samples drawn 2-, 4-, and 6-hours after [51Cr]CrEDTA injection (246-GFR). GFR was also measured using the SI method with samples at 2 and 4 hours (24-GFR) and at 4 and 6 hours (46-GFR), and SS methods according to Groth (4Gr-GFR) and Fleming (4Fl-GFR). Statistical analysis was performed to assess the accuracy, precision, and bias of the methods. RESULTS: Mean 246-GFR was 79.2 ± 21.9 mL/min/1.73 m2. ANOVA indicated a significant difference between 4Gr-GFR and the reference 246-GFR. Bias was lower than 5 mL/min/1.73 m2 for all methods, except for SS methods in subgroups BMI > 40 kg/m2; GFR > 105 or < 45. Precision was adequate and accuracy of 30 % was above 98% for all methods, except for SS methods in subgroup GFR < 45. CONCLUSION: 46-GFR and 246-GFR have high agreement and may be used to evaluate kidney function in patients with solid tumors. Single-sample methods can be adopted in specific situations, for non-obese patients with expected normal GFR.

Impact of baseline and interim quantitative PET parameters on outcomes of classical Hodgkin Lymphoma.

Currently, analysis of interim PET (iPET) according to the Deauville score (DS) is the most important predictive factor in Hodgkin lymphoma (HL); however, there is room for improvement in its prognostic power. This study aimed to evaluate the prognostic value of quantitative PET analysis (maximum standard uptake value [SUVmax], total metabolic tumor volume [TMTV] and total lesion glicolysis [TLG]) at baseline (PET0) and iPET in a retrospective cohort of newly diagnosed classical HL. For positive iPET (+ iPET), the reduction of quantitative parameters in relation to PET0 (ΔSUVmax, ΔTMTV and ΔTLG) was calculated. Between 2011 and 2017, 234 patients treated with ABVD were analyzed. Median age was 30 years-old, 59% had advanced stage disease, 57% a bulky mass and 25% a + iPET (DS 4-5). At baseline, high TLG was associated with an increased cumulative incidence of failure (CIF) (p = 0.032) while neither SUVmax, TMTV or TLG were associated with overall survival (OS) or progression-free survival (PFS). In multivariate analysis, only iPET was associated with CIF (p < 0.001). Among ΔSUVmax, ΔTMTV and ΔTLG, only a ΔSUVmax ≥ 68.8 was significant for PFS (HR: 0.31, CI95%: 0.11-0.86, p = 0.024). A subset of patients with improved PFS amongst + iPET was identified by the quantitative (ΔSUVmax ≥ 68.8%) analysis. In this real-world Brazilian cohort, with prevalent high-risk patients, quantitative analysis of PET0 did not demonstrate to be prognostic, while a dynamic approach incorporating the ΔSUVmax to + iPET succeeded in refining a subset with better prognosis. These findings warrant validation in larger series and indicate that not all patients with + iPET might need treatment intensification.

Comparison of plasma clearance of [51Cr]CrEDTA based on three, two and single samples to measure the glomerular filtration rate in patients with solid tumors: a prospective cross-sectional analysis

Abstract Objectives: [51Cr]CrEDTA is used to measure the Glomerular Filtration Rate (GFR) in different clinical conditions. However, there is no consensus on the ideal number of blood samples to be taken and at what time points to measure its clearance. This study aimed to compare Slope Intercept (SI) and Single-Sample (SS) methods for measuring GFR in patients with solid tumors, stratified by age, GFR, and Body Mass Index (BMI). Methods: 1,174 patients with cancer were enrolled in this prospective study. GFR was calculated by the SI method using blood samples drawn 2-, 4-, and 6-hours after [51Cr]CrEDTA injection (246-GFR). GFR was also measured using the SI method with samples at 2 and 4 hours (24-GFR) and at 4 and 6 hours (46-GFR), and SS methods according to Groth (4Gr-GFR) and Fleming (4Fl-GFR). Statistical analysis was performed to assess the accuracy, precision, and bias of the methods. Results: Mean 246-GFR was 79.2 ± 21.9 mL/min/1.73 m2. ANOVA indicated a significant difference between 4Gr-GFR and the reference 246-GFR. Bias was lower than 5 mL/min/1.73 m2 for all methods, except for SS methods in subgroups BMI > 40 kg/m2; GFR > 105 or < 45. Precision was adequate and accuracy of 30 % was above 98% for all methods, except for SS methods in subgroup GFR < 45. Conclusion: 46-GFR and 246-GFR have high agreement and may be used to evaluate kidney function in patients with solid tumors. Single-sample methods can be adopted in specific situations, for non-obese patients with expected normal GFR.

Innate immune cells and myelin profile in multiple sclerosis: a multi-tracer PET/MR study.

PURPOSE: Neuropathological studies have demonstrated distinct profiles of microglia activation and myelin injury among different multiple sclerosis (MS) phenotypes and disability stages. PET imaging using specific tracers may uncover the in vivo molecular pathology and broaden the understanding of the disease heterogeneity. METHODS: We used the 18-kDa translocator protein (TSPO) tracer (R)-[11C]PK11195 and [11C]PIB PET images acquired in a hybrid PET/MR 3 T system to characterize, respectively, the profile of innate immune cells and myelin content in 47 patients with MS compared to 18 healthy controls (HC). For the volume of interest (VOI)-based analysis of the dynamic data, (R)-[11C]PK11195 distribution volume (VT) was determined for each subject using a metabolite-corrected arterial plasma input function while [11C]PIB distribution volume ratio (DVR) was estimated using a reference region extracted by a supervised clustering algorithm. A voxel-based analysis was also performed using Statistical Parametric Mapping. Functional disability was evaluated by the Expanded Disability Status Scale (EDSS), Multiple Sclerosis Functional Composite (MSFC), and Symbol Digit Modality Test (SDMT). RESULTS: In the VOI-based analysis, [11C]PIB DVR differed between patients and HC in the corpus callosum (P = 0.019) while no differences in (R)-[11C]PK11195 VT were observed in patients relative to HC. Furthermore, no correlations or associations were observed between both tracers within the VOI analyzed. In the voxel-based analysis, high (R)-[11C]PK11195 uptake was observed diffusively in the white matter (WM) when comparing the progressive phenotype and HC, and lower [11C]PIB uptake was observed in certain WM regions when comparing the relapsing-remitting phenotype and HC. None of the tracers were able to differentiate phenotypes at voxel or VOI level in our cohort. Linear regression models adjusted for age, sex, and phenotype demonstrated that higher EDSS was associated with an increased (R)-[11C]PK11195 VT and lower [11C]PIB DVR in corpus callosum (P = 0.001; P = 0.023), caudate (P = 0.015; P = 0.008), and total T2 lesion (P = 0.007; P = 0.012), while better cognitive scores in SDMT were associated with higher [11C]PIB DVR in the corpus callosum (P = 0.001), and lower (R)-[11C]PK11195 VT (P = 0.013). CONCLUSIONS: Widespread innate immune cells profile and marked loss of myelin in T2 lesions and regions close to the ventricles may occur independently and are associated with disability, in both WM and GM structures.

Effects of exercise training on brain metabolism and cognitive functioning in sleep apnea.

Impaired glucose metabolism reflects neuronal/synaptic dysfunction and cognitive function decline in patients with obstructive sleep apnea (OSA). The study investigated the extent to which exercise training (ET) improves cerebral metabolic glucose rate (CMRgl) and cognitive function in patients with OSA. Patients with moderate to severe OSA were randomly assigned to ET (3 times/week, n = 23) or no intervention (control, n = 24). Echocardiography and apolipoprotein ε4 (APOEε4) genotyping were obtained at baseline. Both groups underwent cardiopulmonary exercise testing, polysomnography, cognitive tests, brain magnetic resonance imaging, and 18F-fluoro-2-deoxy-D-Glucose positron emission tomography (18FDG-PET) at baseline and study end. Compared with control, exercise-trained group had improved exercise capacity, decreased apnea-hypopnea index (AHI), oxygen desaturation and arousal index; increased attention/executive functioning, increased CMRgl in the right frontal lobe (P < 0.05). After ET an inverse relationships occurred between CMRgl and obstructive AHI (r = - 0.43, P < 0.05) and apnea arousal index (r = - 0.53, P < 0.05), and between the changes in CMRgl and changes in mean O2 saturation during sleep and non-rapid eye movement sleep (r = - 0.43, P < 0.05), desaturation during arousal (r = - 0.44, P < 0.05), and time to attention function testing (r = - 0.46, P < 0.05). ET improves OSA severity and CMRg in the frontal lobe, which helps explain the improvement in attention/executive functioning. Our study provides promising data that reinforce the growing idea that ET may be a valuable tool to prevent hypoxia associated with decreased brain metabolism and cognitive functioning in patients with moderate to severe OSA.Trial registration: NCT02289625 (13/11/2014).

Is there a role for diagnostic scans in the management of intermediate-risk thyroid cancer?

Radioiodine (RAI) is selectively recommended for intermediate-risk differentiated thyroid carcinomas (DTC). The information gleaned from pretherapy stimulated thyroglobulin levels (sTg) and diagnostic 131I whole-body scans (DxWBS) to guide therapy remains controversial. The present study aimed at evaluating the impact of preablation sTg and DxWBS in the management of intermediate-risk DTC. A retrospective analysis of 301 intermediate-risk DTC patients submitted to total thyroidectomy and RAI therapy was performed. Pretherapy sTg and DxWBS and post-therapy WBS (RxWBS) findings were analyzed and compared to outcomes. Fifty-two patients (17.3%) had metastases diagnosed by DxWBS and/or RxWBS. The DxWBS identified 10.6% of patients with functioning metastases, including unexpected distant metastases. If combined with SPECT-CT, DxWBS detected RAI-avid metastases more frequently, particularly lymph node metastases (13.1% vs 4.2% planar WBS, P = 0.015). The DxWBS findings modified patient management in 8.3%. A pretherapy sTg <1 ng/mL was associated with a low false-negative rate for the presence of metastases (5.2%), and its performance in excluding metastasis was improved by a negative DxWBS (2.7% of patients with both negative exams had metastases in RxWBS). A sTg <1 ng/mL predicted statistically significant lower rates of recurrent/persistent disease and biochemical/structural incomplete responses. In conclusion, preablation sTg and DxWBS contribute to the detection of unknown or persistent metastatic disease in intermediate-risk DTC patients. A sTg <1 ng/mL in combination with a negative DxWBS is highly suggestive of the absence of remaining malignant disease, and one may consider deferring RAI ablation if both exams are negative. A stunning effect is rarely observed and it does not impair proper treatment of metastases.

Value of Primary Rectal Tumor PET/MRI in the Prediction of Synchronic Metastatic Disease.

PURPOSE: To analyze the associations between positron emission tomography (PET)/magnetic resonance imaging (MRI) features for primary rectal tumors and metastases. PROCEDURES: Between November 2016 and April 2018, 101 patients with rectal adenocarcinoma were included in this prospective study (NCT02537340) for whole-body PET/MRI for baseline staging. Two readers analyzed the PET/MRI; they assessed the semiquantitative PET features of the primary tumor and the N- and M-stages. Another reader analyzed the MRI features for locoregional staging. The reference standard for confirming metastatic disease was biopsy or imaging follow-up. Non-parametric tests were used to compare the PET/MRI features of the participants with or without metastatic disease. Binary logistic regression was used to evaluate the associations between the primary tumor PET/MRI features and metastatic disease. RESULTS: A total of 101 consecutive participants (median age 62 years; range: 33-87 years) were included. Metastases were detected in 35.6% (36 of 101) of the participants. Among the PET/MRI features, higher tumor lesion glycolysis (352.95 vs 242.70; P = .46) and metabolic tumor volume (36.15 vs 26.20; P = .03) were more frequent in patients with than in those without metastases. Additionally, patients with metastases had a higher incidence of PET-positive (64% vs 32%; P = .009) and MRI-positive (56% vs 32%; P = .03) mesorectal lymph nodes, extramural vascular invasion (86% vs 49%; P > .001), and involvement of mesorectal fascia (64% vs 42%; P = .04); there were also differences between the mrT stages of these two groups (P = .008). No differences in the maximum standardized uptake values for the primary tumors in patients with and without metastases were observed (18.9 vs 19.1; P = .56). Multivariable logistic regression showed that extramural vascular invasion on MRI was the only significant predictor (adjusted odds ratio, 3.8 [95% CI: 1.1, 13.9]; P = .001). CONCLUSION: PET/MRI facilitated the identification of participants with a high risk of metastatic disease, though these findings were based mainly on MRI features.

Persistent symptoms and decreased health-related quality of life after symptomatic pediatric COVID-19: A prospective study in a Latin American tertiary hospital.

OBJECTIVES: To prospectively evaluate demographic, anthropometric and health-related quality of life (HRQoL) in pediatric patients with laboratory-confirmed coronavirus disease 2019 (COVID-19). METHODS: This was a longitudinal observational study of surviving pediatric post-COVID-19 patients (n=53) and pediatric subjects without laboratory-confirmed COVID-19 included as controls (n=52) was performed. RESULTS: The median duration between COVID-19 diagnosis (n=53) and follow-up was 4.4 months (0.8-10.7). Twenty-three of 53 (43%) patients reported at least one persistent symptom at the longitudinal follow-up visit and 12/53 (23%) had long COVID-19, with at least one symptom lasting for >12 weeks. The most frequently reported symptoms at the longitudinal follow-up visit were headache (19%), severe recurrent headache (9%), tiredness (9%), dyspnea (8%), and concentration difficulty (4%). At the longitudinal follow-up visit, the frequencies of anemia (11% versus 0%, p=0.030), lymphopenia (42% versus 18%, p=0.020), C-reactive protein level of >30 mg/L (35% versus 0%, p=0.0001), and D-dimer level of >1000 ng/mL (43% versus 6%, p=0.0004) significantly reduced compared with baseline values. Chest X-ray abnormalities (11% versus 2%, p=0.178) and cardiac alterations on echocardiogram (33% versus 22%, p=0.462) were similar at both visits. Comparison of characteristic data between patients with COVID-19 at the longitudinal follow-up visit and controls showed similar age (p=0.962), proportion of male sex (p=0.907), ethnicity (p=0.566), family minimum monthly wage (p=0.664), body mass index (p=0.601), and pediatric pre-existing chronic conditions (p=1.000). The Pediatric Quality of Live Inventory 4.0 scores, median physical score (69 [0-100] versus 81 [34-100], p=0.012), and school score (60 [15-100] versus 70 [15-95], p=0.028) were significantly lower in pediatric patients with COVID-19 at the longitudinal follow-up visit than in controls. CONCLUSIONS: Pediatric patients with COVID-19 showed a longitudinal impact on HRQoL parameters, particularly in physical/school domains, reinforcing the need for a prospective multidisciplinary approach for these patients. These data highlight the importance of closer monitoring of children and adolescents by the clinical team after COVID-19.

Whole Skeletal Mean SUV Measured on 18F-NaF PET/CT Studies as a Prognostic Indicator in Patients with Bone Metastatic Breast Cancer.

In this work we assessed the association between the whole skeletal mean standardized uptake value (SUV) measured on 18F-NaF PET/CT studies and the overall survival (OS) of bone metastatic breast cancer patients. Methods: We retrospectively analyzed 176 patients with breast cancer and bone metastatic disease who performed 18F-NaF PET/CT studies. The outcomes of the patients (dead or alive) were established based on the last information available on their files. The mean and maximum SUVs were measured in a whole skeletal volume of interest (wsVOI). The wsVOI was defined based on the CT component of the PET/CT study using Hounsfield Units thresholds. The wsVOI was then applied on the 18F-NaF PET image. Univariate analyses were performed to assess the association of the SUVs with OS. We also analyzed the association of the age of the patients, the presence of visceral metastatic disease, histological subtypes, presence of hormone receptors, human epidermal growth factor receptor 2 expression and the creatinine, CA15-3 and alkaline phosphatase (ALP) levels with OS. The variables statistically significant in the univariate analyses were included in a multivariate cox regression survival analysis. Results: In the univariate analyses there were associations of the mean and maximum whole skeletal SUVs, estrogen receptor status and the CA15-3 and ALP levels with OS. In the multivariate analysis, all the variables that were statistically significant in the univariate analysis but the CA15-3 were associated with OS. Conclusion: In patients with bone metastatic breast cancer, the whole skeletal mean SUV is an independent predictor of overall survival.

99mTechnetium- or Cy7-Labeled Fab(Tocilizumab) as Potential Multiple Myeloma Imaging Agents.

BACKGROUND: Multiple Myeloma (MM) is a malignant hematologic disorder and the second most common blood cancer. Interleukin-6 (IL-6) has been identified as a crucial factor for the proliferation and survival of MM cells and the overexpression of IL-6 receptor is being studied as a molecular target for therapeutic and diagnostic use in myelomas and other comorbidities. Tocilizumab is a humanized monoclonal antibody that binds IL-6R. OBJECTIVE: We aim to label and evaluate Fab(Tocilizumab) with 99mTechnetium or Cy7 as potential MM imaging agents. METHODS: IL-6R distribution was analyzed by Laser Confocal Microscopy (LCM) in MM cell lines. Fab(Tocilizumab) was produced by the digestion of Tocilizumab with papain for 24h at 37°C, derivatized with NHS-HYNIC-Tfa and radiolabeled with 99mTc. Radiochemical stability and in vitro cell assays were evaluated. Biodistribution and SPECT/CT were performed. Also, Fab(Tocilizumab) was labeled with Cy7 for in vivo fluorescence imaging up to 72h. RESULTS: LCM analysis demonstrates IL-6R distribution on MM cell lines. Incubation with papain resulted in complete digestion of Tocilizumab and exhibited a good purity and homogeneity. Radiolabeling with 99mTc via NHS-HYNIC-Tfa was found to be fast, easy, reproducible and stable, revealing high radiochemical purity and without interfering with IL-6R recognition. Biodistribution and SPECT/CT studies showed a quick blood clearance and significant kidney and MM engrafted tumor uptake. Cy7-Fab(Tocilizumab) fluorescent imaging allowed MM1S tumor identification up to 72h p.i. CONCLUSION: These new molecular imaging agents could potentially be used in the clinical setting for staging and follow-up of MM through radioactive whole-body IL-6R expression visualization in vivo. The fluorescent version could be used for tissue sample evaluation and to guide surgical excision, if necessary.

Combined effects of theta-burst stimulation with transcranial direct current stimulation of the prefrontal cortex: study protocol of a randomized, double-blinded, sham-controlled trial using 99mTc-ECD SPECT.

INTRODUCTION: Non-invasive brain stimulation (NIBS) as monotherapy has been increasingly used to enhance the activity of brain networks. However, it is unclear whether a combination of distinct NIBS approaches could enhance prefrontal cortical (PFC) activity. OBJECTIVE: We propose to investigate the combined and standalone effects of two NIBS modalities on the PFC through a working memory task, single photon emission computed tomography (SPECT), and salivary cortisol. We hypothesize that the combined protocol will provoke greater changes in the collected measures compared to the remining protocols. METHODS: A randomized, double-blind, sham-controlled, full-factorial design will be conducted. The effects of transcranial direct current stimulation (tDCS) and intermittent theta-burst stimulation (iTBS) will be investigated over four different sessions (sham tDCS + sham iTBS, anodal tDCS + sham iTBS, anodal tDCS + active iTBS and sham tDCS + active iTBS) in 30 healthy adult volunteers. A 99mTc-ethylene cysteine dimer (99mTC-ECD) will be administered during the NIBS session and neuroimaging will be acquired within one hour. Salivary cortisol will be collected before and after each session and an n-back working memory task will be applied after the end of each NIBS session. The outcomes will be cerebral perfusion alterations (99mTC-ECD SPECT), accuracy and reaction time in the n-back task, and changes in salivary cortisol level. CONCLUSION: The results from this trial can guide future therapeutic protocols for NIBS treatments stimulating the PFC by demonstrating that the combination of NIBS techniques is feasible, tolerable, and can lead to greater enhancement of PFC activity.

Diagnostic accuracy of FDG-PET/MRI versus pelvic MRI and thoracic and abdominal CT for detecting synchronous distant metastases in rectal cancer patients.

PURPOSE: We compared the diagnostic accuracy of detecting distant metastases for baseline rectal cancer staging between PET/MRI and conventional staging (CS). MATERIALS AND METHODS: This prospective study from November 2016 to April 2018 included 101 rectal adenocarcinoma patients for primary staging. These patients underwent whole-body PET/MRI in addition to CS (pelvic MRI and thoracic and abdominal contrast-enhanced CT). Different readers analyzed CS and PET/MRI findings for primary tumor, nodal, and metastatic staging. The presence, number, and location of metastases were recorded according to the organ involved (non-regional lymph nodes (LNs), liver, lungs, or others). Lesions were defined as positive, negative, or indeterminate. The number of lesions per organ was limited to 10. The McNemar test was used to compare the accuracies. RESULTS: PET/MRI exhibited a higher accuracy in detecting metastatic disease than CS in all patients (88.4% vs. 82.6%, p = 0.003) and in patients with extramural vascular invasion (EMVI) (88.9% vs. 85.5%, p = 0.013). The detection rate of PET/MRI was superior to that of CS for all lesions [84.1% vs. 68.9%, p = 0.001], as well as those in the liver (89.2% vs. 84.2%), non-regional LNs (90.0% vs. 36.7%), and lungs (76.4% vs. 66.9%). PET/MRI correctly classified 19/33 (57.5%) patients with indeterminate lesions on CS. CONCLUSION: PET/MRI yields higher accuracy than CS for detecting distant synchronous metastases in the baseline staging of patients with rectal cancer and EMVI. PET/MRI exhibited a higher detection rate than CS for identifying non-regional LNs, hepatic lesions, and pulmonary lesions as well as correctly classifying patients with indeterminate lesions. TRIAL REGISTRATION: NCT02537340.

PET/MRI Characterization of Mucinous Versus Nonmucinous Components of Rectal Adenocarcinoma: A Comparison of Tumor Metabolism and Cellularity.

OBJECTIVE. The purpose of this study was to evaluate whether FDG PET/MRI can be used to differentiate the mucinous from the nonmucinous components of primary rectal tumors and to compare the glycolytic metabolism on PET with tumor cellularity on DWI in both components. SUBJECTS AND METHODS. Ninety-nine patients who underwent FDG PET/MRI for staging of primary rectal cancer were included in this prospective analysis. MRI depicted the mucin component through the tumor volume. Separate volumes of interest were drawn on both mucinous and nonmucinous components and propagated to PET and apparent diffusion coefficient (ADC) mapping. Maximum and mean standardized uptake values (SUVmax, SUVmean) and maximum, mean, and minimum ADC values (ADCmax, ADCmean, ADCmin) were recorded and compared between areas with mucinous and nonmucinous components. Whole-body PET/MRI was also used to evaluate for the presence of distant metastases. Nonparametric testing was used to compare the two groups of patients: those with tumors with a mucinous component and those with tumors without a mucinous component. Logistic regression analysis was performed to calculate the association risk between mucinous component and metastatic disease. RESULTS. Seventeen patients (17.2%) had a mucinous component within the tumor on T2-weighted MRI. Most of these patients had advanced disease, the mucinous component tumors being in significantly higher T categories than the tumors without a mucinous component (88.2% vs 61.0%; p = 0.032). SUVmax (7.4 vs 16.7; p = 0.002) and SUVmean (5.4 vs 13.4; p = 0.001) were significantly lower in tumors with a mucinous component than in those without a mucinous component. Tumor ADC measurements were not different between tumors with and those without a mucinous component (ADCmean, 1.4 vs 1.6; p = 0.361). There was no association between presence of a mucinous component within the primary rectal tumor and presence of synchronous metastases (odds ratio, 1.1 [0.4-3.0]; p = 0.904). Moreover, the occurrence of metastases in patients with mucinous component tumors (7/17 [41.2%]) was not different from that in patients with tumors without a mucinous component (28/82 [34.1%]) (p = 0.887). CONCLUSION. PET/MRI can be used to differentiate the mucinous and nonmucinous components within primary rectal adenocarcinoma on the basis of metabolic status. The FDG uptake is significantly lower in the mucinous component, but tumor cellularity based on MRI and DWI findings is not. Despite being associated with a higher T category in the sample of patients in this study, the presence of a mucinous component seems not to be associated with increased risk of synchronous metastases.

Persistent symptoms and decreased health-related quality of life after symptomatic pediatric COVID-19: A prospective study in a Latin American tertiary hospital

OBJECTIVES: To prospectively evaluate demographic, anthropometric and health-related quality of life (HRQoL) in pediatric patients with laboratory-confirmed coronavirus disease 2019 (COVID-19) METHODS: This was a longitudinal observational study of surviving pediatric post-COVID-19 patients (n=53) and pediatric subjects without laboratory-confirmed COVID-19 included as controls (n=52) was performed. RESULTS: The median duration between COVID-19 diagnosis (n=53) and follow-up was 4.4 months (0.8-10.7). Twenty-three of 53 (43%) patients reported at least one persistent symptom at the longitudinal follow-up visit and 12/53 (23%) had long COVID-19, with at least one symptom lasting for >12 weeks. The most frequently reported symptoms at the longitudinal follow-up visit were headache (19%), severe recurrent headache (9%), tiredness (9%), dyspnea (8%), and concentration difficulty (4%). At the longitudinal follow-up visit, the frequencies of anemia (11% versus 0%, p=0.030), lymphopenia (42% versus 18%, p=0.020), C-reactive protein level of >30 mg/L (35% versus 0%, p=0.0001), and D-dimer level of >1000 ng/mL (43% versus 6%, p=0.0004) significantly reduced compared with baseline values. Chest X-ray abnormalities (11% versus 2%, p=0.178) and cardiac alterations on echocardiogram (33% versus 22%, p=0.462) were similar at both visits. Comparison of characteristic data between patients with COVID-19 at the longitudinal follow-up visit and controls showed similar age (p=0.962), proportion of male sex (p=0.907), ethnicity (p=0.566), family minimum monthly wage (p=0.664), body mass index (p=0.601), and pediatric pre-existing chronic conditions (p=1.000). The Pediatric Quality of Live Inventory 4.0 scores, median physical score (69 [0-100] versus 81 [34-100], p=0.012), and school score (60 [15-100] versus 70 [15-95], p=0.028) were significantly lower in pediatric patients with COVID-19 at the longitudinal follow-up visit than in controls. CONCLUSIONS: Pediatric patients with COVID-19 showed a longitudinal impact on HRQoL parameters, particularly in physical/school domains, reinforcing the need for a prospective multidisciplinary approach for these patients. These data highlight the importance of closer monitoring of children and adolescents by the clinical team after COVID-19.

Therapeutic Efficiency of Multiple Applications of Magnetic Hyperthermia Technique in Glioblastoma Using Aminosilane Coated Iron Oxide Nanoparticles: In Vitro and In Vivo Study.

Magnetic hyperthermia (MHT) has been shown as a promising alternative therapy for glioblastoma (GBM) treatment. This study consists of three parts: The first part evaluates the heating potential of aminosilane-coated superparamagnetic iron oxide nanoparticles (SPIONa). The second and third parts comprise the evaluation of MHT multiple applications in GBM model, either in vitro or in vivo. The obtained heating curves of SPIONa (100 nm, +20 mV) and their specific absorption rates (SAR) stablished the best therapeutic conditions for frequencies (309 kHz and 557 kHz) and magnetic field (300 Gauss), which were stablished based on three in vitro MHT application in C6 GBM cell line. The bioluminescence (BLI) signal decayed in all applications and parameters tested and 309 kHz with 300 Gauss have shown to provide the best therapeutic effect. These parameters were also established for three MHT applications in vivo, in which the decay of BLI signal correlates with reduced tumor and also with decreased tumor glucose uptake assessed by positron emission tomography (PET) images. The behavior assessment showed a slight improvement after each MHT therapy, but after three applications the motor function displayed a relevant and progressive improvement until the latest evaluation. Thus, MHT multiple applications allowed an almost total regression of the GBM tumor in vivo. However, futher evaluations after the therapy acute phase are necessary to follow the evolution or tumor total regression. BLI, positron emission tomography (PET), and spontaneous locomotion evaluation techniques were effective in longitudinally monitoring the therapeutic effects of the MHT technique.

Preserved repetition in thalamic afasia. A pathophysiological hypothesis.

The ability to repeat words is almost always preserved in thalamic aphasia. The pathophysiology of both thalamic aphasia and preservation of repetition are not fully understood. In a case of severe aphasia with preserved repetition after a left thalamic hemorrhage, MRI disclosed left thalamic lesion and loss of fractional anisotropy in the left centrum semiovale. FDG-PET showed severe hypometabolism in the left cerebral hemisphere, except for superior and transverse temporal gyri, calcarine fissure and frontopolar regions. Primary sensory function may be less functionally dependent on thalamic connections than heteromodal and paralimbic areas, which have connections with several thalamic nuclei. The extensive cortical hypometabolism due to diaschisis may have been responsible for the severity of the aphasia, whereas the less severe reduction of metabolism in the superior and transverse temporal gyri, and also, albeit less evident, in Broca's area, might explain the preservation of repetition.

A capacidade de repetir palavras é quase sempre preservada na afasia talâmica. A fisiopatologia da afasia talâmica assim como a da preservação da repetição não são totalmente compreendidas. Em um caso de afasia grave com repetição preservada após hemorragia talâmica esquerda, a RM revelou lesão talâmica esquerda e perda de anisotropia fracionada no centro semioval. O FDG-PET revelou hipometabolismo grave no hemisfério cerebral esquerdo, exceto nos giros temporais superiores e transversos, fissura calcarina e regiões frontopares. A função sensorial primária pode ser menos funcionalmente dependente das conexões talâmicas do que as áreas heteromodais e paralímbicas, que têm conexões com vários núcleos talâmicos. O hipometabolismo cortical extenso devido à diasquise pode ter sido responsável pela gravidade da afasia, enquanto a redução menos severa do metabolismo nos giros temporal superior e transverso, e também, embora menos evidente, na área de Broca, poderia explicar a preservação da repetição.

[11C]PIB PET imaging can detect white and grey matter demyelination in a non-human primate model of progressive multiple sclerosis.

BACKGROUND: Multiple sclerosis (MS) is a demyelinating and inflammatory disease of the central nervous system. Its diagnosis is clinical, often confirmed by magnetic resonance imaging. This image modality, however, is not ideal for discrimination of demyelination in grey and white matter regions from inflammatory lesions. Positron Emission Tomography (PET), using specific radiopharmaceuticals, can be a tool to differentiate between these processes. The radiopharmaceutical [11C]PIB is widely used for detection of ß-amyloid plaques, but has also been suggested for the analysis of myelin content due to its consistent uptake in white matter. The aim of this study was to evaluate [11C]PIB PET imaging as a tool for detecting demyelinated regions in white and grey matter of non-human primate model of progressive MS. METHODS: Experimental autoimmune encephalomyelitis (EAE) was induced in marmosets by injection of recombinant human myelin oligodendrocyte glycoprotein (rhMOG) emulsified in either Incomplete Freund's Adjuvant (IFA) or Complete Freund's Adjuvant (CFA). [11C]PIB PET images were acquired prior to immunization (baseline) and after symptoms were present (end of experiment). Brain tissue was isolated for histochemical analysis. RESULTS: All rhMOG/IFA-treated and rhMOG/CFA-treated animals showed clinical signs of EAE. The rhMOG/CFA group presented a significant [11C]PIB uptake reduction only in the left motor cortex (9%, P = 0.011). For the rhMOG/IFA group, significant decrease in [11C]PIB uptake was observed in the whole brain (15%, P = 0.015), in the right hemisphere of body of corpus callosum (34%, P = 0.02), splenium of corpus callosum (38%, P = 0.004), hippocampus (19%, P = 0.036), optic tract (13%, P = 0.025), thalamus (14%, P = 0.041), Globus pallidus (23%, P = 0.017), head of caudate nucleus (25%, P = 0.045), tail of caudate nucleus (29%, P = 0.003), putamen (28%, P = 0.047) and left hemisphere of body of corpus callosum (14%, P = 0.037) and head of caudate nucleus (23%, P = 0.023). [11C]PIB uptake significantly correlated with luxol fast blue histology (myelin marker), both in the rhMOG/IFA (r2= 0.32, P < 0.0001) and the rhMOG/CFA group (r2= 0.46, P < 0.0001). CONCLUSION: [11C]PIB PET imaging is an efficient tool for detecting demyelination in grey and white matter, in a non-human primate model of progressive MS.

68Ga-DOTATATE PET: temporal variation of maximum standardized uptake value in normal tissues and neuroendocrine tumours.

OBJECTIVES: Higher affinity of Ga compounds to somatostatin receptors (SSTRs) and PET better image resolution increased interest in Ga-labelled somatostatin analogs in the management of neuroendocrine tumours (NETs). This study aimed to evaluate the maximum standardized uptake value (SUVmax) variation in sequential somatostatin analogs-PET in NET patients and identify optimal tumour detection and characterization imaging time. METHODS: Patients with histological or biochemical NET diagnosis performed two to three PET/computed tomography (CT) scans after intravenous injection of Ga-DOTATATE: Early PET [EarlyPET: <15 minutes postinjection (p.i.)], diagnostic PET (DiagPET: 45-90 minutes p.i.) and delayed PET (DelayPE: 90-240 minutes p.i.). Up to five tumour sites and normal tissues had SUVmax determined. Time-SUVmax curves were created for the target lesions and normal organs. Ratios between tumour and liver SUVmax (SUVTU/Liver) and tumour/blood pool (SUVTU/BP) were also calculated. RESULTS: Twenty-nine patients were included, 16 female, mean age of 46.5 ± 14.3 years. Average administered activity was 129.5 ± 29.6 MBq. Kidneys SUVmax was higher in EarlyPET compared with DiagPET (P = 0.04) and DelayPET showed higher SUVmax compared with DiagPET for normal liver, pancreas and kidneys (P = 0.02). No differences were noted between EarlyPET, DiagPET and DelayPET in tumour SUVmax (P > 0.05). SUVTU/Liver and SUVTU/BP did not change between EarlyPET and DiagPET, with a slight decrease in DelayPET. CONCLUSION: Stability in tumour SUVmax values measured at different intervals independently of tumour location, as also in normal tissues as kidneys and liver suggest that a more flexible imaging protocol may be adopted.