Evidence of brain metabolism redistribution from neocortex to primitive brain structures in early acute COVID-19 respiratory syndrome.

BACKGROUND: Neuropsychiatric sequelae of COVID-19 have been widely documented in patients with severe neurological symptoms during the chronic or subacute phase of the disease. However, it remains unclear whether subclinical changes in brain metabolism can occur early in the acute phase of the disease. The aim of this study was to identify and quantify changes in brain metabolism in patients hospitalized for acute respiratory syndrome due to COVID-19 with no or mild neurological symptoms. RESULTS: Twenty-three non-intubated patients (13 women; mean age 55.5 ± 12.1 years) hospitalized with positive nasopharyngeal swab test (RT-PCR) for COVID-19, requiring supplemental oxygen and no or mild neurological symptoms were studied. Serum C-reactive protein measured at admission ranged from 6.43 to 189.0 mg/L (mean: 96.9 ± 54.2 mg/L). The mean supplemental oxygen demand was 2.9 ± 1.4 L/min. [18F]FDG PET/CT images were acquired with a median of 12 (4-20) days of symptoms. After visual interpretation of the images, semiquantitative analysis of [18F]FDG uptake in multiple brain regions was evaluated using dedicated software and the standard deviation (SD) of brain uptake in each region was automatically calculated in comparison with reference values of a normal database. Evolutionarily ancient structures showed positive SD mean values of [18F]FDG uptake. Lenticular nuclei were bilaterally hypermetabolic (> 2 SD) in 21/23 (91.3%) patients, and thalamus in 16/23 (69.6%), bilaterally in 11/23 (47.8%). About half of patients showed hypermetabolism in brainstems, 40% in hippocampi, and 30% in cerebellums. In contrast, neocortical regions (frontal, parietal, temporal and occipital lobes) presented negative SD mean values of [18F]FDG uptake and hypometabolism (< 2 SD) was observed in up to a third of patients. Associations were found between hypoxia, inflammation, coagulation markers, and [18F]FDG uptake in various brain structures. CONCLUSIONS: Brain metabolism is clearly affected during the acute phase of COVID-19 respiratory syndrome in neurologically asymptomatic or oligosymptomatic patients. The most frequent finding is marked hypermetabolism in evolutionary ancient structures such as lenticular nucleus and thalami. Neocortical metabolism was reduced in up to one third of patients, suggesting a redistribution of brain metabolism from the neocortex to evolutionary ancient brain structures in these patients.

Interictal and postictal 18F-FDG PET/CT in epileptogenic zone localization.

Objective: To evaluate the performance of 18F-fluorodeoxyglucose positron-emission tomography/computed tomography ( 18F-FDG PET/CT) in localizing epileptogenic zones, comparing 18F-FDG injection performed in the traditional interictal period with that performed near the time of a seizure. Materials and Methods: We evaluated patients with refractory epilepsy who underwent 18F-FDG PET/CT. The reference standards for localization of the epileptogenic zone were histopathology and follow-up examinations (in patients who underwent surgery) or serial electroencephalography (EEG) recordings, long-term video EEG, and magnetic resonance imaging (in patients who did not). The 18F-FDG injection was performed whether the patient had an epileptic seizure during the EEG monitoring period or not. The 18F-FDG PET/CT results were categorized as concordant or discordant with the reference standards. Results: Of the 110 patients evaluated, 10 were in a postictal group (FDG injection after a seizure) and 100 were in the interictal group. The 18F-FDG PET/CT was concordant with the reference standards in nine (90%) of the postictal group patients and in 60 (60%) of the interictal group patients. Among the nine postictal group patients in whom the results were concordant, the 18F-FDG PET/CT showed hypermetabolism and hypometabolism in the epileptogenic zone in four (44.4%) and five (55.6%), respectively. Conclusion: Our data indicate that 18F-FDG PET/CT is a helpful tool for localization of the epileptogenic zone and that EEG monitoring is an important means of correlating the findings. In addition, postictal 18F-FDG PET/CT is able to identify the epileptogenic zone by showing either hypometabolism or hypermetabolism.

Objetivo: Avaliar a capacidade da PET/CT FDG detectar a zona epileptogênica, com injeção da FDG realizada tanto no período interictal como perto de uma crise epiléptica. Materiais e Métodos: Foram avaliados pacientes com epilepsia de difícil controle que realizaram PET/CT FDG. A zona epileptogênica foi definida pelo follow up/anatomopatológico ou eletroencefalogramas (EEGs) seriados, telemetria e ressonância magnética. PET/CT FDG foi realizada independentemente se o paciente tinha crise epiléptica durante a monitoração com EEG ou no período interictal. Os resultados foram definidos como concordantes ou discordantes, comparando com a zona epileptogênica. Resultados: Foram incluídos no estudo 110 pacientes: 10 no grupo pós-ictal (injeção de FDG depois da crise) e 100 no grupo interictal. A PET/CT FDG foi concordante com a zona epileptogênica em nove pacientes do grupo pós-ictal (90%) e 60 pacientes do grupo interictal (60%). Entre os nove pacientes concordantes do grupo pós-ictal, quatro mostraram hipermetabolismo (44,4%) e cinco mostraram hipometabolismo na zona epileptogênica (55,6%). Conclusão: Nossos resultados confirmaram que a PET/CT FDG é uma ferramenta útil na localização da zona epileptogênica e a monitoração com EEG é muito importante para correlacionar os achados. Além disso, PET/CT FDG realizada no período pós-ictal é capaz de identificar a zona epileptogênica, mostrando tanto hipometabolismo como hipermetabolismo.

Interictal and postictal 18F-FDG PET/CT in epileptogenic zone localization / PET/CT FDG- 18F interictal e pós-ictal na localização da zona epileptogênica

Abstract Objective: To evaluate the performance of 18F-fluorodeoxyglucose positron-emission tomography/computed tomography ( 18F-FDG PET/CT) in localizing epileptogenic zones, comparing 18F-FDG injection performed in the traditional interictal period with that performed near the time of a seizure. Materials and Methods: We evaluated patients with refractory epilepsy who underwent 18F-FDG PET/CT. The reference standards for localization of the epileptogenic zone were histopathology and follow-up examinations (in patients who underwent surgery) or serial electroencephalography (EEG) recordings, long-term video EEG, and magnetic resonance imaging (in patients who did not). The 18F-FDG injection was performed whether the patient had an epileptic seizure during the EEG monitoring period or not. The 18F-FDG PET/CT results were categorized as concordant or discordant with the reference standards. Results: Of the 110 patients evaluated, 10 were in a postictal group (FDG injection after a seizure) and 100 were in the interictal group. The 18F-FDG PET/CT was concordant with the reference standards in nine (90%) of the postictal group patients and in 60 (60%) of the interictal group patients. Among the nine postictal group patients in whom the results were concordant, the 18F-FDG PET/CT showed hypermetabolism and hypometabolism in the epileptogenic zone in four (44.4%) and five (55.6%), respectively. Conclusion: Our data indicate that 18F-FDG PET/CT is a helpful tool for localization of the epileptogenic zone and that EEG monitoring is an important means of correlating the findings. In addition, postictal 18F-FDG PET/CT is able to identify the epileptogenic zone by showing either hypometabolism or hypermetabolism.

Resumo Objetivo: Avaliar a capacidade da PET/CT FDG detectar a zona epileptogênica, com injeção da FDG realizada tanto no período interictal como perto de uma crise epiléptica. Materiais e Métodos: Foram avaliados pacientes com epilepsia de difícil controle que realizaram PET/CT FDG. A zona epileptogênica foi definida pelo follow up/anatomopatológico ou eletroencefalogramas (EEGs) seriados, telemetria e ressonância magnética. PET/CT FDG foi realizada independentemente se o paciente tinha crise epiléptica durante a monitoração com EEG ou no período interictal. Os resultados foram definidos como concordantes ou discordantes, comparando com a zona epileptogênica. Resultados: Foram incluídos no estudo 110 pacientes: 10 no grupo pós-ictal (injeção de FDG depois da crise) e 100 no grupo interictal. A PET/CT FDG foi concordante com a zona epileptogênica em nove pacientes do grupo pós-ictal (90%) e 60 pacientes do grupo interictal (60%). Entre os nove pacientes concordantes do grupo pós-ictal, quatro mostraram hipermetabolismo (44,4%) e cinco mostraram hipometabolismo na zona epileptogênica (55,6%). Conclusão: Nossos resultados confirmaram que a PET/CT FDG é uma ferramenta útil na localização da zona epileptogênica e a monitoração com EEG é muito importante para correlacionar os achados. Além disso, PET/CT FDG realizada no período pós-ictal é capaz de identificar a zona epileptogênica, mostrando tanto hipometabolismo como hipermetabolismo.

Lithium Intoxication as a cause of reversible dementia mimicking FDG PET features of Alzheimer's disease.

Rapidly progressive dementia (RPD) is a rare neurological disorder. Drug toxicity is among the differential diagnoses, including the use of lithium, in which an overdosage might cause cognitive dysfunction. Clinical suspicion, laboratory confirmation, and drug interruption are key points in the management of lithium intoxication. We described a 66-year-old female patient under treatment with lithium who developed an RPD associated with parkinsonian symptoms. 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) showed an "Alzheimer-like" pattern, while cerebrospinal fluid biomarkers for the disease were negative. There was a significant clinical and radiological improvement after lithium interruption. Lithium intoxication is a potentially reversible cause of RPD, as demonstrated in this case report. Drug discontinuation should be considered even in patients with normal levels of this metal, if cognitive impairment is detected. 18F-FDG PET/CT images may show an "Alzheimer-like" image pattern in acute intoxication and are useful for monitoring these patients.

Demência rapidamente progressiva é uma condição rara, cujos diagnósticos diferenciais incluem intoxicação por drogas como lítio, podendo causar importante disfunção cognitiva. A suspeita clínica, a confirmação laboratorial e a interrupção do uso medicamentoso são elementos fundamentais em seu diagnóstico e manejo. Trata-se de paciente feminina, de 66 anos de idade, que apresentou quadro demencial após intoxicação por lítio. Tal quadro foi acompanhado de sintomas parkinsonianos, além de Tomografia por Emissão de Pósitrons com 18F-Fluodeoxiglicose (18F-FDG PET/CT) compatível com padrão "Alzheimer-like". Houve melhora objetiva de parâmetros clínicos e imaginológicos após a interrupção do uso medicamentoso. A intoxicação por lítio é uma causa potencialmente reversível de demência rapidamente progressiva. A descontinuação da droga deve ser considerada também em pacientes com níveis normais do metal no sangue se alterações cognitivas forem encontradas. Imagens 18F-FDG PET/CT podem demonstrar achados sugestivos de doença de Alzheimer na intoxicação aguda e parecem ser um método útil no seguimento.

Lithium Intoxication as a cause of reversible dementia mimicking FDG PET features of Alzheimer's disease / Intoxicação por lítio como causa de demência rapidamente progressiva: um relato de caso e revisão da literatura

ABSTRACT. Rapidly progressive dementia (RPD) is a rare neurological disorder. Drug toxicity is among the differential diagnoses, including the use of lithium, in which an overdosage might cause cognitive dysfunction. Clinical suspicion, laboratory confirmation, and drug interruption are key points in the management of lithium intoxication. We described a 66-year-old female patient under treatment with lithium who developed an RPD associated with parkinsonian symptoms. 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) showed an "Alzheimer-like" pattern, while cerebrospinal fluid biomarkers for the disease were negative. There was a significant clinical and radiological improvement after lithium interruption. Lithium intoxication is a potentially reversible cause of RPD, as demonstrated in this case report. Drug discontinuation should be considered even in patients with normal levels of this metal, if cognitive impairment is detected. 18F-FDG PET/CT images may show an "Alzheimer-like" image pattern in acute intoxication and are useful for monitoring these patients.

RESUMO. Demência rapidamente progressiva é uma condição rara, cujos diagnósticos diferenciais incluem intoxicação por drogas como lítio, podendo causar importante disfunção cognitiva. A suspeita clínica, a confirmação laboratorial e a interrupção do uso medicamentoso são elementos fundamentais em seu diagnóstico e manejo. Trata-se de paciente feminina, de 66 anos de idade, que apresentou quadro demencial após intoxicação por lítio. Tal quadro foi acompanhado de sintomas parkinsonianos, além de Tomografia por Emissão de Pósitrons com 18F-Fluodeoxiglicose (18F-FDG PET/CT) compatível com padrão "Alzheimer-like". Houve melhora objetiva de parâmetros clínicos e imaginológicos após a interrupção do uso medicamentoso. A intoxicação por lítio é uma causa potencialmente reversível de demência rapidamente progressiva. A descontinuação da droga deve ser considerada também em pacientes com níveis normais do metal no sangue se alterações cognitivas forem encontradas. Imagens 18F-FDG PET/CT podem demonstrar achados sugestivos de doença de Alzheimer na intoxicação aguda e parecem ser um método útil no seguimento.

Body mass variability in age-matched outbred male Swiss mice is associated to differential control of food intake by ghrelin.

Swiss mice belong to an outbred strain of mice largely used as a model for experimental obesity induced by high fat diet (HFD). We have previously demonstrated that a given cohort of age-matched Swiss mice is hallmarked by heterogeneous changes in body weight when exposed to HFD. The reasons underlying such variability, however, are not completely understood. Therefore we aimed to clarify the mechanisms underlying the variability in spontaneous weight gain in age-matched male swiss mice. To achieve that, individuals in a cohort of age-matched male Swiss mice were categorized as prone to body mass gain (PBMG) and resistant to body mass gain (RBMG). PBMG animals had higher caloric intake and body mass gain. RBMG and PBMG mice had a similar reduction in food intake when challenged with leptin but only RBMG exhibited a drop in ghrelin concentrations after refeeding. PBMG also showed increased midbrain levels of ghrelin receptor (Ghsr) and Dopamine receptor d2 (Drd2) mRNAs upon refeeding. Pharmacological blockade of GHSR with JMV3002 failed to reduce food intake in PMBG mice as it did in RBMG. On the other hand, the response to JMV3002 seen in PBMG was hallmarked by singular transcriptional response in the midbrain characterized by a simultaneous increase in both tyrosine hydroxylase (Th) and Proopiomelanocortin (Pomc) expressions. In conclusion, our data show that differences in the expression of genes related to the reward system in the midbrain as well as in ghrelin concentrations in serum correlate with spontaneous variability in body mass and food intake seen in age-matched male Swiss mice.

Combined training increases thermogenic fat activity in patients with overweight and type 2 diabetes.

BACKGROUND: Exercise is an important strategy in the management of diabetes. Experimental studies have shown that exercise acts, at least in part, by inducing the production of myokines that improve metabolic control and activate brown/beige adipose tissue depots. Combined training (CT) is recommended by the major diabetes guidelines due to its metabolic and cardiovascular benefits, however, its impact on brown/beige adipose tissue activities has never been tested in humans with overweight and type 2 diabetes (T2D). Here, we evaluated the effects of 16-week combined training (CT) program on brown adipose tissue activity; browning and autophagy markers, and serum pro-thermogenic/inflammatory inducers in patients with overweight and T2D. METHODS: Thirty-four patients with overweight and T2D were assigned to either a control group (CG) or a combined training group (CTG) in a randomized and controlled study. Functional/fitness parameters, anthropometry/body composition parameters, blood hormone/biochemical parameters, thermogenic/autophagic gene expression in subcutaneous adipose tissue were evaluated before and at the end of the intervention. In addition, cold-induced 18-Fluoroxyglucose Positron Emission Computed Tomography (18F-FDG PET/CT) was performed in the training group before and after the end of the intervention. RESULTS: CT increased cervical/supraclavicular brown adipose tissue (BAT) thermogenic activity (p = 0.03) as well as in perirenal adipose tissue (p = 0.02). In addition, CT increased the expression of genes related to thermogenic profile (TMEM26: + 95%, p = 0.04; and EPSTI1: + 26%, p = 0.03) and decreased autophagic genes (ULK1: -15%, p = 0.04; LC3: -5%, p = 0.02; and ATG4: -22%, p < 0.001) in subcutaneous adipose tissue. There were positive correlations between Δ% BAT activity with Δ% of post training energy expenditure cold exposure, HDL-c, IL4, adiponectin, irisin, meteorin-like, and TMEM26 and ZIC1 genes, besides negative correlations with LDL-c, total cholesterol and C-reactive protein. CONCLUSION: This is the first evidence of the beneficial actions of CT on adipose tissue thermogenic activity in humans, and it adds important support for the recommendation of CT as a strategy in the management of diabetes.

Multimodality Molecular Imaging in Arthropathy Associated with Multiple Myeloma.

We report a patient with multiple myeloma (MM) and polyarthritis of large joints. During the staging of the disease, bone marrow diffusely involved by MM was clearly demonstrated by 99mTc-2-methoxy-isobutyl-isonitrile (MIBI) single-photon emission computed tomography/computed tomography (SPECT/CT) but not by 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/CT images. On the other hand, a very intense uptake of 18F-FDG was detected in periarticular tissues of multiple joints, with nonabnormal 99mTc-MIBI accumulation. Rheumatology tests were negative. A subsequent bone scintigraphy demonstrated radiolabeled bisphosphonate accumulation in periarticular tissues, suggesting amyloid arthropathy.

18F-FDG PET/CT in Late Acquisition Identifies Sites of Active Disease in Treated Takayasu Arteritis.

OBJECTIVE: Few studies have taken advantage of 18F-fluorodeoxyglucose positron emission tomography associated with computed tomography (18F-FDG PET/CT) to personalize patient evaluation and identify sites of more active disease in Takayasu arteritis (TA)-treated patients. This study aimed to evaluate the utility of 18F-FDG PET/CT in late acquisition in identifying sites of active disease in patients under full treatment for TA. METHODS: In this cross-sectional study, patients under full treatment underwent whole-body 18F-FDG PET/CT. Sites of increased 18F-FDG uptake were classified by a score of 3 on the visual scale using the liver uptake as reference. A quantitative analysis was also performed by measuring the maximum standardized uptake value (SUV) of the vascular wall of affected arteries. Disease activity using the National Institutes of Health criteria was also evaluated. RESULTS: Of the 20 patients, there were 18 female and 2 male patients, with a mean age of 43.6 (±11.58) years and a disease duration of 8.3 (±6.25) years. Thirteen participants (65%) were in inflammatory activity according to the criteria proposed by the National Institutes of Health. All patients received immunosuppressive agents, and one of them received immunobiological treatment. The highest SUV value was 6.2 in the aortic arch, and the lowest was 1.0 in the subclavian artery. The mean maximum SUV did not differ between clinically active and inactive patients. In the visual analysis, all participants had at least 1 vascular site with inflammatory activity, with an uptake ≥2 in relation to the liver. The aortic arch was the most frequently involved site. CONCLUSIONS: This study showed that 18F-FDG PET/CT in late acquisition is an effective imaging method to assess TA activity even in fully treated patients.

Metabolic Volume Measurements in Multiple Myeloma.

Multiple myeloma (MM) accounts for 10-15% of all hematologic malignancies, as well as 20% of deaths related to hematologic malignant tumors, predominantly affecting bone and bone marrow. Positron emission tomography/computed tomography with 18F-fluorodeoxyglucose (FDG-PET/CT) is an important method to assess the tumor burden of these patients. It is often challenging to classify the extent of disease involvement in the PET scans for many of these patients because both focal and diffuse bone lesions may coexist, with varying degrees of FDG uptake. Different metrics involving volumetric parameters and texture features have been proposed to objectively assess these images. Here, we review some metabolic parameters that can be extracted from FDG-PET/CT images of MM patients, including technical aspects and predicting MM outcome impact. Metabolic tumor volume (MTV) and total lesion glycolysis (TLG) are volumetric parameters known to be independent predictors of MM outcome. However, they have not been adopted in clinical practice due to the lack of measuring standards. CT-based segmentation allows automated, and therefore reproducible, calculation of bone metabolic metrics in patients with MM, such as maximum, mean and standard deviation of the standardized uptake values (SUV) for the entire skeleton. Intensity of bone involvement (IBI) is a new parameter that also takes advantage of this approach with promising results. Other indirect parameters obtained from FDG-PET/CT images, such as visceral adipose tissue glucose uptake and subcutaneous adipose tissue radiodensity, may also be useful to evaluate the prognosis of MM patients. Furthermore, the use and quantification of new radiotracers can address different metabolic aspects of MM and may have important prognostic implications.

Head-to-head comparison between 68Ga-PSMA and 18F-FDG-PET/CT in lymphomas: a preliminary analysis.

PURPOSE: Isolated case reports mention the uptake of radiolabeled PSMA in lymphoma. However, it is not clear if the intensity of 68Ga-PSMA expression varies among different histological subtypes or if it correlates with 18F-FDG uptake. This study compared both tracers in patients with diverse lymphoma subtypes. METHODS: Ten patients with biopsy-proven-lymphoma underwent 18F-FDG and 68Ga-PSMA-PET/CT (maximum time interval: 6 days). Lymphoma subtypes included Hodgkin's lymphoma (HL, three patients) and aggressive and indolent non-Hodgkin's lymphoma (NHL, seven patients). The intensity of PSMA uptake was classified visually as low, intermediate, or high, using blood pool, liver and parotid gland uptake as references. Maximum standardized-uptake value (SUVmax) of each affected site was measured in both sets of images. RESULTS: FDG detected 59/59 involved sites in 10 patients and PSMA 47/59 sites in nine patients. PSMA uptake was generally low, regardless of the intensity of FDG uptake, but it was classified as intermediate in two patients. The median SUVmax varied from 2.0 (2.0-8.2) to 30.9 for FDG and from 1.7 (1.7-1.7) to 4.4 for PSMA, P < 0.0001. The primary lesion of one patient had a marked intralesional mismatch uptake pattern of the tracers, with areas of higher PSMA expression than FDG uptake, and vice-versa. A brain lesion was more easily identified with PSMA than with FDG images. CONCLUSION: HL and several NHL subtypes may present PSMA uptake. The intensity of PSMA expression is generally lower than that of FDG uptake and seems to present less variation among the different histological subtypes of lymphomas.

Visceral adipose tissue glucose uptake is linked to prognosis in multiple myeloma patients: An exploratory study.

BACKGROUND & AIMS: The use of computerized tomography to opportunistically assess body composition has highlighted abnormalities such as low muscle mass and high adiposity may be hidden conditions in cancer patients. However, the role of skeletal muscle (SM), subcutaneous (SAT) and visceral (VAT) adipose tissue glucose uptake measured by 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)-CT on patient prognostication is unclear. METHODS: Patients with multiple myeloma (MM) with satisfactory image frame for assessing body composition and for semi-quantification of SM, SAT and VAT glucose uptakes were included. Plasmatic pro-inflammatory cytokine and adipokine levels were measured. RESULTS: High VAT mean standardized uptake value (SUV) at baseline was associated with shorter event-free survival (EFS) (hazard ratio [HR]: 7.89; 95% confidence interval [CI], 1.58-39.30; P = 0.012) and overall survival (OS) (HR, 15.24; 95% CI, 2.69-86.30; P = 0.002) among patients with newly diagnosed MM, even after adjustment for covariates. The highest tertile of VAT SUV was significantly correlated with worse MM-EFS (HR for the highest vs the lowest tertile 3.71; 95% CI, 1.22-10.56; Ptrend = 0.035) and mortality (HR, 4.41; 95% CI, 1.28-12.77; Ptrend = 0.019). Notably, patients with higher VAT SUV presented with lower VAT area, VAT index, higher SAT SUV, and higher number of individuals with visceral obesity (all P < 0.01). Additionally, we found a negative correlation between VAT mean SUV with leptin (R2 = 0.20, P = 0.003); no correlations were detected between VAT mean SUV and resistin, tumor necrosis factor (TNF) or interleukin (IL)-6. CONCLUSIONS: Functional VAT activity estimated by 18F-FDG PET-CT is a relevant prognostic factor in MM patients, specifically, a higher VAT SUV might be an early biomarker of cancer cachexia in these patients.

Adipose tissue radiodensity: A new prognostic biomarker in people with multiple myeloma.

OBJECTIVES: Standard prognostic markers based on individual characteristics of individuals with multiple myeloma (MM) remain scarce. Body-composition features have often been associated with survival outcomes in different cancers. However, the association of adipose tissue radiodensity with MM prognosis has not yet, to our knowledge, been explored. METHODS: Computed tomography at the third lumbar vertebra was used for body-composition analysis, including adipose tissue radiodensity, in 91 people with MM. Additionally, fludeoxyglucose F 18 (18F-FDG) positron emission tomography was used to assess adipose tissue 18F-FDG uptake. Proinflammatory cytokine and adipokine levels were measured. RESULTS: Event-free survival and overall survival were both shorter in participants with high subcutaneous adipose tissue (SAT) radiodensity. Those in the highest SAT radiodensity tertile had an independently higher risk for both overall survival (hazard ratio, 4.55; 95% confidence interval, 1.26-16.44; Ptrend = 0.036) and event-free survival (hazard ratio, 3.08; 95% confidence interval, 1.02-9.27; Ptrend = 0.035). Importantly, higher SAT radiodensity was significantly correlated with increased 18F-FDG adipose tissue uptake and proinflammatory cytokine (tumor necrosis factor and interleukin-6) levels, and with decreased leptin levels. CONCLUSIONS: SAT radiodensity may serve as a biomarker to predict host-related metabolic and proinflammatory milieu, which ultimately correlates with MM prognosis.

Fixed 30 mCi (1110 MBq) 131I-iodine therapy in autonomously functioning nodules: Single toxic nodule as a predictive factor of success.

AIMS: The aim of this study is to evaluate the efficacy of a fixed 30 mCi (1110 MBq) 131I-iodine dose for the treatment of hyperthyroidism due to uninodular or multinodular toxic goiter and identify predictors of success. MATERIALS AND METHODS: Fifty-nine patients diagnosed with nonautoimmune toxic goiter were treated with a fixed 30 mCi dose of 131I-iodine and were followed at a tertiary service between 2000 and 2016. The therapy was considered successful if the patient reached euthyroidism or hypothyroidism without needing an extra 131I-iodine dose or antithyroid drugs for at least 1 year after the radioiodine therapy (RIT). RESULTS: Patients with a single toxic nodule were younger at diagnosis (52 vs. 63 years; P = 0.007), presented a shorter disease duration until RIT (2 vs. 3.5 years; P = 0.007), smaller total thyroid volume (20 vs. 82 cm3; P = 0.044), and lower pre-RIT thyroid uptake (P = 0.043) than patients with multinodular goiter. No significant difference was seen with antithyroid drug use, thyroid-stimulating hormone and free thyroxine level, and follow-up after RIT. After RIT, 47 patients (79.66%) met the success criteria, and 12 (20.33%) remained hyperthyroid. Among the success group, 32 (68.08%) reached euthyroidism, while 31.92% developed hypothyroidism after 1 year. Patients with single toxic nodules who achieved success after RIT presented smaller nodules (2.8 vs. 5.75 cm; P = 0.043), while the pre-RIT thyroid uptake was higher among patients with multinodular toxic goiter who achieved success after RIT (5.5% vs. 1.5%; P = 0.007). A higher success rate was observed among patients with a single toxic nodule than those with a toxic multinodular goiter (92.3% vs. 55%; P = 0.001), and a single toxic nodule presentation was found to be an independent predictor of success (P = 0.009). CONCLUSIONS: The fixed 30 mCi 131I-iodine dose was particularly effective in the group of patients with single autonomously functioning nodule rather than the group with multiple nodules. A single toxic nodule was an independent predictor of treatment success.

FAS and FASL variations in outcomes of tobacco- and alcohol-related head and neck squamous cell carcinoma patients.

Radiotherapy and cisplatin lead to cell killing in head and neck squamous cell carcinoma patients, but adverse events and response to treatment are not the same in patients with similar clinicopathological aspects. The aim of this prospective study was to evaluate the roles of TP53 c.215G > C, FAS c.-671A > G, FAS c.-1378G > A, FASL c.-844 C > T, CASP3 c.-1191A > G, and CASP3 c.-182-247G > T single nucleotide variants in toxicity, response rate, and survival of cisplatin chemoradiation-treated head and neck squamous cell carcinoma patients. Genomic DNA was analyzed by polymerase chain reaction for genotyping. Differences between groups of patients were analyzed by chi-square test or Fisher's exact test, multiple logistic regression analysis, and Cox hazards model. One hundred nine patients with head and neck squamous cell carcinoma were enrolled in study. All patients were smokers and/or alcoholics. Patients with FAS c.-671GG genotype, FAS c.-671AG or GG genotype, and FASL c.-844CC genotype had 5.52 (95% confidence interval (CI): 1.42-21.43), 4.03 (95% CI: 1.51-10.79), and 5.77 (95% CI: 1.23-27.04) more chances of presenting chemoradiation-related anemia of grades 2-4, lymphopenia of grade 3 or 4, and ototoxicity of all grades, respectively, than those with the remaining genotypes. FAS c.-671GG genotype was also seen as an independent predictor of shorter event-free survival (hazard ratio (HR): 2.05; P = 0.007) and overall survival (HR: 1.83; P = 0.02) in our head and neck squamous cell carcinoma patients. These findings present, for the first time, preliminary evidence that inherited abnormalities in apoptosis pathway, related to FAS c.-671A > G and FASL c.-844 C > T single nucleotide variants, can alter toxicity and survival of tobacco- and alcohol-related head and neck squamous cell carcinoma patients homogeneously treated with cisplatin chemoradiation.

Clinical Usefulness of SISCOM-SPM Compared to Visual Analysis to Locate the Epileptogenic Zone.

Introduction: Subtraction of ictal-interictal SPECT co-registered to MRI (SISCOM) is a quantification tool that can improve the sensitivity and specificity of the epileptogenic zone (EZ) localization. Commercially available image analysis software packages for SISCOM are costly, and Statistical Parametric Mapping (SPM) could be an alternative free software for the definition of the EZ. There are only a few studies that compare SISCOM using SPM (SISCOM-SPM) with visual analysis. Aim: To compare SISCOM-SPM vs. visual analysis for localization of the EZ in patients with pharmacoresistant focal epilepsies. Materials and methods: We evaluated all our patients with focal epilepsies that underwent ictal and interictal SPECT. We defined the reference standard to locate the EZ by pathology and follow-up (in patients submitted to surgery), or seizure semiology, serial EEG, long-term video-EEG, 18F-FDG PET/CT, and MRI (in patients who were not operated). We compared the location of the EZ by visual analysis of SPECT images and by SISCOM-SPM to the reference standard and classified as concordant, discordant, or partially concordant. Results: We included 23 patients. Visual analysis was concordant with the EZ reference standard in only 13 patients (56.5%), while SISCOM-SPM was concordant in 18 cases (78.3%), providing a 21.8% increase in the location of EZ. However, this difference was not significant due to the small sample size (p = 0.0856). Conclusion: Our preliminary results demonstrate that, in clinical practice, SISCOM-SPM has the potential to add information that might help localize the EZ compared to visual analysis. SISCOM-SPM has a lower cost than other commercially available SISCOM software packages, which is an advantage for developing countries. Studies with more patients are necessary to confirm our findings.