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PURPOSE: In routine care, clinicians may employ 2-[18F]fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET) computed tomography (CT) to validate their initial clinical diagnosis of polymyalgia rheumatica (PMR). Nevertheless, the diagnostic utility of combining FDG-PET/CT findings with clinical presentation has not been explored. Therefore, this study aimed to investigate whether the diagnostic accuracy for PMR could be enhanced by combining FDG-PET/CT findings with the clinical baseline diagnosis or the 2012 ACR/EULAR clinical classification criteria for PMR. METHODS: An investigation and a validation cohort were included from two countries, encompassing 66/27 and 36/21 PMR/non-PMR patients, respectively. The cohorts comprised treatment-naïve patients suspected of PMR, who initially received a clinical baseline diagnosis and underwent FDG-PET/CT scans. The FDG-PET/CT Leuven-score was applied to classify patients as either PMR or non-PMR and combined with the clinical baseline diagnosis. Final diagnoses were established through clinical follow-up after twelve or six months in the investigation and validation cohorts, respectively. RESULTS: In the investigation cohort, a clinical baseline diagnosis yielded a sensitivity/specificity of 94%/82%, compared with 78%/70% using the ACR/EULAR criteria. Combining the clinical baseline diagnosis with a positive Leuven-score showed a sensitivity/specificity of 80%/93%, compared with 80%/82% for an ACR/EULAR-Leuven-score. In the validation cohort, the baseline diagnosis revealed a sensitivity/specificity of 100%/91%, compared with 92%/76% using the ACR/EULAR criteria. Combining FDG-PET/CT with the baseline diagnosis demonstrated a sensitivity/specificity of 83%/95% compared with 89%/81% for the ACR/EULAR-Leuven-score. CONCLUSION: Combining FDG-PET/CT findings with the clinical baseline diagnosis or ACR/EULAR clinical classification criteria can improve the diagnostic specificity for PMR.
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PURPOSE: 2-[18F]Fluoro-2-deoxy-D-glucose (FDG)-positron emission tomography (PET)/computed tomography (CT) has been suggested as an imaging modality to diagnose polymyalgia rheumatica (PMR). However, the applicability of FDG-PET/CT remains unclear, especially following glucocorticoid administration. This study aimed to investigate the diagnostic accuracy of FDG-PET/CT before and during prednisolone treatment, as well as following short-term prednisolone discontinuation. METHODS: Treatment naïve suspected PMR patients were clinically diagnosed at baseline and subsequently had an FDG-PET/CT performed. Patients diagnosed with PMR were administered prednisolone following the first FDG-PET/CT and had a second FDG-PET/CT performed after 8 weeks of treatment. Subsequently, prednisolone was tapered with short-term discontinuation at week 9 followed by a third FDG-PET/CT at week 10. An FDG-PET/CT classification of PMR/non-PMR was applied, utilizing both the validated Leuven score and a dichotomous PMR score. The final diagnosis was based on clinical follow-up after 1 year. RESULTS: A total of 68 and 27 patients received a final clinical diagnosis of PMR or non-PMR. A baseline FDG-PET/CT classified the patients as having PMR with a sensitivity/specificity of 86%/63% (Leuven score) and 82%/70% (dichotomous score). Comparing the subgroup of non-PMR with inflammatory diseases to the PMR group demonstrated a specificity of 39%/54% (Leuven/dichotomous score). After 8 weeks of prednisolone treatment, the sensitivity of FDG-PET/CT decreased to 36%/41% (Leuven/dichotomous score), while a short-term prednisolone discontinuation increased the sensitivity to 66%/60%. CONCLUSION: FDG-PET/CT has limited diagnostic accuracy for differentiating PMR from other inflammatory diseases. If FDG-PET/CT is intended for diagnostic purposes, prednisolone should be discontinued to enhance diagnostic accuracy. TRIAL REGISTRATION: ClinicalTrials.gov (NCT04519580). Registered 17th of August 2020.
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Fluordesoxiglucose F18 , Polimialgia Reumática , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Prednisolona , Humanos , Polimialgia Reumática/diagnóstico por imagem , Polimialgia Reumática/tratamento farmacológico , Prednisolona/uso terapêutico , Prednisolona/administração & dosagem , Masculino , Feminino , Idoso , Estudos Prospectivos , Pessoa de Meia-Idade , Idoso de 80 Anos ou mais , Suspensão de Tratamento , Compostos Radiofarmacêuticos , Sensibilidade e EspecificidadeRESUMO
BACKGROUND: Evaluation of sufficient adenosine response constitutes a significant challenge in myocardial perfusion imaging (MPI). Splenic switch-off in MPI studies denotes a visually (qualitatively) reduced splenic radiotracer signal during adenosine stress and is considered indicative of sufficient cardiac vasodilation. In this study, we examined semi-quantitative and quantitative approaches to splenic switch-off assessment using [15O]H2O-PET with either summed activity images or calculated parametric splenic blood flow images. METHODS: Cohort 1: 90 clinical patients undergoing [15O]H2O MPI in whom adenosine response was considered clinically adequate were identified to characterize the corresponding splenic switch-off. Spleen stress/rest-ratio (SSR-ratio) was calculated as spleen stress signal intensity/spleen rest signal intensity on both summed activity and parametric blood flow images. Cohort 2: Twenty-five patients with repeat MPI due to suspected insufficient adenosine response were identified to observe if splenic switch-off on the initial MPI could predict the outcome of the repeat MPI. Cohort 3: Fifty-four patients who were considered adenosine responders on MPI and who had a coronary angiogram (CAG) follow-up within 3 months after MPI served as a separate validation group. RESULTS: Splenic switch-off was present in most patients with a clinically sufficient adenosine response (Cohort 1), illustrated by both visual (74.4%-86.7%), semi-quantitative (summed activity images) (85.6%), and quantitative (parametric blood flow images) (92.2%) evaluation, which corresponds to the distribution in patients with sufficient adenosine response and follow-up CAG (Cohort 3). In patients suspected of insufficient adenosine response on the initial MPI (Cohort 2), the repeat MPI only yielded different myocardial blood flow (MBF) results if the initial SSR-ratio was >0.90 on splenic parametric blood flow images. CONCLUSION: quantitative splenic switch-off assessment on parametric blood flow images was superior to the semi-quantitative splenic switch-off approach. Patients with a suspected insufficient initial adenosine response and SSR-ratio >0.90 can benefit from a repeat MPI. Thus, the integration of quantitative splenic switch-off using parametric blood flow images in the evaluation of adenosine response may support future clinical decision-making.
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BACKGROUND: Coincidental extracardiac findings with increased perfusion were reported during myocardial perfusion imaging (MPI) with various retention radiotracers. Clinical parametric O-15-H2O PET MPI yielding quantitative measures of myocardial blood flow (MBF) was recently implemented at our facility. We aim to explore whether similar extracardiac findings are observed using O-15-H2O. METHODS AND RESULTS: All patients (2963) were scanned with O-15-H2O PET MPI according to international guidelines and extracardiac findings were collected. In contrast to parametric O-15-H2O MBF images, extracardiac perfusion was assessed using summed images. Biopsy histopathology and other imaging modalities served as reference standards. Various malignant lesions with increased perfusion were detected, including lymphomas, large-celled neuroendocrine tumour, breast, and lung cancer plus metastases from colonic and renal cell carcinomas. Furthermore, inflammatory and hyperplastic benign conditions with increased perfusion were observed: rib fractures, gynecomastia, atelectasis, sarcoidosis, pneumonia, chronic lung inflammation and fibrosis, benign lung nodule, chronic diffuse lung infiltrates, pleural plaques and COVID-19 infiltrates. CONCLUSIONS: Malignant and benign extracardiac coincidental findings with increased perfusion are readily visible and frequently seen on O-15-H2O PET MPI. We recommend evaluating the summed O-15-H2O PET images in addition to the low-dose CT attenuation images.
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COVID-19 , Imagem de Perfusão do Miocárdio , Masculino , Humanos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Imagem de Perfusão do Miocárdio/métodos , Perfusão , Tomografia por Emissão de Pósitrons/métodosRESUMO
OBJECTIVES: The diagnostic accuracy of axillary artery US in the diagnosis of large-vessel (LV)-GCA using 18F-fluorodeoxyglucose (FDG) PET/CT as reference standard was prospectively evaluated in GCA-suspected patients. As an exploratory analysis, the diagnostic accuracy of cranial artery FDG PET/CT was evaluated. METHODS: Briefly, the inclusion criteria were age ≥50 years, raised inflammatory markers and potential GCA symptoms. Patients in immunosuppressive therapy or with a previous diagnosis of GCA or PMR were excluded. Examinations were performed pre-treatment. LV-GCA reference diagnosis was a clinical diagnosis of GCA and PET-proven LV inflammation. GCA patients fulfilling ACR criteria were considered as cranial-GCA (c-GCA). Patients without GCA were considered controls. Receiver operating characteristic curve analysis of the US-measured axillary intima-media thickness was performed. FDG uptake in temporal, maxillary and vertebral arteries was also assessed. RESULTS: Forty-six patients were diagnosed with LV-GCA, 10 with isolated c-GCA, and in 34 patients GCA was dismissed. Axillary US yielded a sensitivity of 76% and a specificity of 100% for LV-GCA. An axillary intima-media thickness cut-off of 1.0 mm yielded a sensitivity of 74% and a specificity of 92%. Adding LV US to temporal assessment increased sensitivity from 71% to 97% (all GCA patients). Cranial artery PET showed a diagnostic sensitivity of 78% and specificity of 100% for c-GCA. CONCLUSION: Axillary artery US shows high accuracy for the LV-GCA diagnosis. Building upon the recent EULAR recommendations, we propose a diagnostic algorithm with US as the first-line confirmatory test, not only in c-GCA-suspected patients, but in all patients suspected of GCA.
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Arterite de Células Gigantes/diagnóstico por imagem , Artérias Temporais/diagnóstico por imagem , Idoso , Idoso de 80 Anos ou mais , Feminino , Fluordesoxiglucose F18 , Humanos , Masculino , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Estudos Prospectivos , Sensibilidade e Especificidade , UltrassonografiaRESUMO
BACKGROUND: Coronary computed tomography angiography (CTA) is the preferred primary diagnostic modality when examining patients with low to intermediate pre-test probability of coronary artery disease (CAD). Only 20-30% of these have potentially obstructive CAD. Because of the relatively poor positive predictive value of coronary CTA, unnecessary invasive coronary angiographies (ICAs) are conducted with the costs and risks associated with the procedure. Hence, an optimized diagnostic CAD algorithm may reduce the numbers of ICAs not followed by revascularization. The Dan-NICAD 2 study has 3 equivalent main aims: (1) To examine the diagnostic precision of a sound-based diagnostic algorithm, The CADScor®System (Acarix A/S, Denmark), in patients with a low to intermediate pre-test risk of CAD referred to a primary examination by coronary CTA. We hypothesize that the CADScor®System provides better stratification prior to coronary CTA than clinical risk stratification scores alone. (2) To compare the diagnostic accuracy of 3T cardiac magnetic resonance imaging (3T CMRI), 82rubidium positron emission tomography (82Rb-PET), and CT-derived fractional flow reserve (FFRCT) in patients where obstructive CAD cannot be ruled out by coronary CTA using ICA fractional flow reserve (FFR) as reference standard. (3) To compare the diagnostic performance of quantitative flow ratio (QFR) and ICA-FFR in patients with low to intermediate pre-test probability of CAD using 82Rb-PET as reference standard. METHODS: Dan-NICAD 2 is a prospective, multicenter, cross-sectional study including approximately 2,000 patients with low to intermediate pre-test probability of CAD and without previous history of CAD. Patients are referred to coronary CTA because of symptoms suggestive of CAD, as evaluated by a cardiologist. Patient interviews, sound recordings, and blood samples are obtained in connection with the coronary CTA. If coronary CTA does not rule out obstructive CAD, patients will be examined by 3T CMRI 82Rb-PET, FFRCT, ICA, and FFR. Reference standard is ICA-FFR. Obstructive CAD is defined as an FFR ≤0.80 or as high-grade stenosis (>90% diameter stenosis) by visual assessment. Diagnostic performance will be evaluated as sensitivity, specificity, predictive values, likelihood ratios, calibration, and discrimination. Enrolment started January 2018 and is expected to be completed by June 2020. Patients are followed for 10 years after inclusion. DISCUSSION: The results of the Dan-NICAD 2 study are expected to contribute to the improvement of diagnostic strategies for patients suspected of CAD in 3 different steps: risk stratification prior to coronary CTA, diagnostic strategy after coronary CTA, and invasive wireless QFR analysis as an alternative to ICA-FFR.
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Angiografia por Tomografia Computadorizada/métodos , Angiografia Coronária/métodos , Doença da Artéria Coronariana/diagnóstico , Reserva Fracionada de Fluxo Miocárdico/fisiologia , Imagem Cinética por Ressonância Magnética/métodos , Tomografia Computadorizada Multidetectores/métodos , Tomografia por Emissão de Pósitrons/métodos , Adulto , Doença da Artéria Coronariana/fisiopatologia , Estudos Transversais , Dinamarca , Feminino , Seguimentos , Humanos , Masculino , Estudos Prospectivos , Reprodutibilidade dos TestesRESUMO
PURPOSE: To estimate the diagnostic accuracy of conventional 18F-FDG PET/CT of cranial arteries in the diagnosis of giant cell arteritis (GCA). METHODS: The study was a retrospective case-control study. The reference diagnosis was fulfillment of the 1990 ACR criteria for GCA. All patients had new-onset GCA. Conventional 18F-FDG PET/CT was performed before glucocorticoid treatment. Controls were age- and sex-matched patients with a previous history of malignant melanoma (MM) undergoing surveillance PET/CT >6 months after MM resection. PET images were evenly cropped to include only head and neck and were assessed in random order by four nuclear medicine physicians blinded to reference diagnosis. Temporal (TA), maxillary (MA) and vertebral (VA) arteries were visually rated for 18F-FDG uptake. Interreader agreement was evaluated by Fleiss kappa. RESULTS: A total of 44 patients and 44 controls were identified. In both groups, the mean age was 69 years (p = 0.45) and 25/44 were women. 35/41 GCA patients were temporal artery biopsy positive (TAB). Considering only FDG uptake in TA and/or MA, diagnostic sensitivity and specificity was 64 and 100%. Including VA, sensitivity increased to 82% and specificity remained 100%. Interreader agreement was 91% and Fleiss kappa 0.82 for the PET diagnosis based on the cranial arteries. CONCLUSION: Conventional 18F-FDG PET/CT is an accurate and reliable tool to diagnose cranial arteritis in glucocorticoid-naïve GCA patients. The high diagnostic specificity suggests that TAB can be omitted in patients with 18F-FDG uptake in cranial arteries. 18F-FDG PET/CT performed in patients with suspected vasculitis should always include the head and neck.
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Arterite de Células Gigantes/diagnóstico por imagem , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/normas , Idoso , Estudos de Casos e Controles , Feminino , Fluordesoxiglucose F18 , Arterite de Células Gigantes/patologia , Humanos , Inflamação , Masculino , Variações Dependentes do Observador , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Compostos Radiofarmacêuticos , Sensibilidade e EspecificidadeRESUMO
AIMS: Metformin is first-line treatment of type 2 diabetes mellitus and reduces cardiovascular events in patients with insulin resistance and type 2 diabetes. Target tissue for metformin action is thought to be the liver, where metformin distribution depends on facilitated transport by polyspecific transmembrane organic cation transporters (OCTs). Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease in the western world with strong associations to insulin resistance and the metabolic syndrome, but whether NAFLD affects metformin biodistribution to the liver is not known. In this study, the primary aim was to investigate in vivo hepatic uptake of metformin dynamically in humans with variable degrees of liver affection. As a secondary aim, we wished to correlate hepatic metformin distribution with OCT gene transcription determined in diagnostic liver biopsies. METHODS: Eighteen patients with biopsy-proven NAFLD were investigated using 11C-metformin PET/CT technique. Gene transcripts of OCTs were determined by real-time polymerase chain reaction (PCR). RESULTS: We observed similar hepatic volume of distribution of metformin between patients with simple steatosis and non-alcoholic steatohepatitis (NASH) (Vd 2.38 ± 0.56 vs. 2.10 ± 0.39, P = 0.3). There was no association between hepatic exposure to metformin and the degree of inflammation or fibrosis, and no clear correlation between metformin distribution and OCT gene transcription. CONCLUSION: Metformin is distributed to the liver in patients with NAFLD and the distribution is not impaired by inflammation or fibrosis. The findings imply that metformin action in liver in patients with NAFLD may be preserved.
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Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/farmacocinética , Fígado/metabolismo , Metformina/farmacocinética , Hepatopatia Gordurosa não Alcoólica/metabolismo , Adulto , Idoso , Biópsia , Radioisótopos de Carbono , Diabetes Mellitus Tipo 2/etiologia , Feminino , Perfilação da Expressão Gênica , Humanos , Hipoglicemiantes/administração & dosagem , Fígado/patologia , Masculino , Metformina/administração & dosagem , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Hepatopatia Gordurosa não Alcoólica/patologia , Proteínas de Transporte de Cátions Orgânicos/genética , Proteínas de Transporte de Cátions Orgânicos/metabolismo , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Distribuição TecidualRESUMO
OBJECTIVES: To investigate the in-situ expression of acetylcholinesterase (AChE) in the inflamed vessel wall of patients with biopsy-positive giant cell arteritis (GCA) as compared to biopsy-negative non-GCA patients, and to evaluate the in-vivo expression of AChE in patients with large-vessel GCA (LVGCA) by 11C-donepezil (AChE inhibitor) positron emission tomography/computed tomography (PET/CT). METHODS: Twenty-four biopsy-positive GCA and 44 biopsy-negative non-GCA patients were included for AChE histology. Immunohistochemical methods were used to determine the AChE expression. The histological inflammation and the AChE expression were assessed by an experienced pathologist on a 3-point scale. Two patients with newly diagnosed 18F-fluorodeoxyglucose (18F-FDG) PET/CT verified LVGCA were included for 11C-donepezil PET/CT. PET images were assessed by an experienced nuclear medicine physician. RESULTS: AChE was expressed in all 24 positive temporal artery biopsies, 10/24 showed high AChE expression (grade 2) and 14/24 showed moderate AChE expression (grade 1). No AChE expression was observed outside the media smooth muscle cells (grade 0) in any of the biopsy-negative non-GCA patients. The AChE expression was in 86% agreement with the histological inflammation. The AChE expression was not associated with any clinical or biochemical findings. In both LV-GCA patients, PET/CT revealed extensive vascular FDG uptake but no 11C-donepezil uptake. CONCLUSIONS: AChE is highly expressed in the inflamed vessel wall of patients with GCA. Although, 11C-donepezil PET/CT showed no vascular uptake in the FDG PET/CT verified LV-GCA patients, histological findings raise the possibility that AChE can be used in the development of new diagnostic and disease monitoring tools for GCA.
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Acetilcolinesterase/metabolismo , Arterite de Células Gigantes , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Radioisótopos de Carbono , Donepezila , Fluordesoxiglucose F18 , Arterite de Células Gigantes/diagnóstico por imagem , Arterite de Células Gigantes/enzimologia , Arterite de Células Gigantes/patologia , Humanos , Inflamação , Compostos RadiofarmacêuticosRESUMO
PURPOSE: To evaluate the in-treatment diagnostic accuracy of FDG PET/CT in large-vessel giant cell arteritis (LV-GCA) by serial scans before and after a short course of high-dose glucocorticoid treatment. METHODS: Twenty-four glucocorticoid-naïve patients with new-onset PET/CT verified LV-GCA (pre-treatment baseline PET) were prospectively included. Excluded were patients with a previous history of GCA or polymyalgia rheumatica, LV-GCA-mimicking conditions and patients on immunosuppressive therapy. All patients were treated with 60 mg of oral prednisolone daily and assigned for in-treatment FDG PET/CT after either 3 (PET3) or 10 days (PET10). Two experienced nuclear medicine physicians, blinded to patients' clinical data, reviewed the FDG PET/CT images. A visual semi-quantitative approach was used. Segmental and homogenous FDG uptake in the wall of the aorta and/or supra-aortic branches with higher uptake intensity than liver was considered consistent with vasculitis. Inter-reader reliability was evaluated. RESULTS: Although glucocorticoid treatment attenuated FDG uptake in large vessels, LV-GCA was accurately diagnosed in 10/10 patients after 3 days of treatment, but only in 5/14 patients after 10 days of treatment (p < 0.001). Interrater reliability was substantial (agreement 87%, Cohen's weighted kappa 0.70). No correlation between CRP and FDG uptake was found. CONCLUSIONS: Within 3 days of high-dose glucocorticoid treatment, FDG PET/CT can diagnose LV-GCA with high sensitivity. This window of opportunity ensures that prompt glucocorticoid treatment can be initiated to avoid debilitating GCA complications with a limited effect on diagnostic accuracy. After 10 days of treatment, FDG PET/CT sensitivity decreases significantly.
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Arterite de Células Gigantes/tratamento farmacológico , Glucocorticoides/uso terapêutico , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Idoso , Idoso de 80 Anos ou mais , Feminino , Fluordesoxiglucose F18 , Humanos , Masculino , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons , Compostos Radiofarmacêuticos , Reprodutibilidade dos TestesRESUMO
According to the updated guidelines for imaging in lymphoma, 18F-FDG positron emission tomography/computed tomography (PET/CT) is recommended for staging and evaluation of treatment response in FDG-avid lymphomas. The purpose of the study was to evaluate the utility of PET/CT in nodal peripheral T-cell lymphomas (PTCL). Patients with newly diagnosed nodal PTCL (peripheral T-cell lymphoma NOS, anaplastic large-cell lymphoma, or angioimmunoblastic T-cell lymphoma) seen at five Danish hematology centers during the period 2006 to 2012 were included, if they had been pretherapeutically staged with PET/CT. Medical records were reviewed for baseline clinical and follow-up information. Staging, interim (I-PET), and end-of-treatment PET/CT (E-PET) studies were centrally reviewed, and reported using the Deauville 5-point score (DS). A total of 124 patients fulfilled the inclusion criteria. The median age was 58 years, and 88% received CHOP/CHOP-like therapy. Five years PFS and OS of the study population was 36.8% (95% CI 27.3-46.4) and 49.7% (95% CI 38.9-59.6), respectively. The presence of PET/CT-ascertained lung and/or liver involvement was associated with a worse outcome. The sensitivity of PET/CT for detecting biopsy-defined bone marrow involvement was only 18% (95% CI 4-43). An interim DS >3 was not prognostic for worse OS and PFS among CHOP/CHOP-like treated patients in uni- or multivariate analyses. A DS >3 after treatment predicted a worse prognosis. In conclusion, I-PET was not predictive of outcome in CHOP/CHOP-like treated PTCL patients when using the DS. Prospective studies are needed to determine the optimal use of PET/CT in PTCL including the role of quantitative PET/CT analysis.
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Protocolos de Quimioterapia Combinada Antineoplásica , Linfoma Difuso de Grandes Células B/diagnóstico por imagem , Linfoma Anaplásico de Células Grandes/diagnóstico por imagem , Linfoma de Células T Periférico/diagnóstico por imagem , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Ciclofosfamida/uso terapêutico , Doxorrubicina/uso terapêutico , Feminino , Fluordesoxiglucose F18 , Humanos , Fígado/diagnóstico por imagem , Fígado/patologia , Pulmão/diagnóstico por imagem , Pulmão/patologia , Linfoma Difuso de Grandes Células B/diagnóstico , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/mortalidade , Linfoma Anaplásico de Células Grandes/diagnóstico , Linfoma Anaplásico de Células Grandes/tratamento farmacológico , Linfoma Anaplásico de Células Grandes/mortalidade , Linfoma de Células T Periférico/diagnóstico , Linfoma de Células T Periférico/tratamento farmacológico , Linfoma de Células T Periférico/mortalidade , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Tomografia por Emissão de Pósitrons , Prognóstico , Estudos Retrospectivos , Análise de Sobrevida , Tomografia Computadorizada por Raios X , Vincristina/uso terapêuticoRESUMO
BACKGROUND: Despite local control now exceeding 90% with image-guided adaptive brachytherapy (IGABT), regional and distant metastases continue to curb survival in locally advanced cervical cancer. As regional lymph nodes often represent first site of metastatic spread, improved nodal control could improve survival. The aim of this study was to examine optimal volume and dose of external beam radiotherapy (EBRT) to maximize regional control including dose contribution from IGABT. MATERIAL AND METHODS: In total 139 patients from the EMBRACE study were analyzed. Individual nodal dose was determined by dose-maps from EBRT and IGABT. All PET/CT scans were re-evaluated and nodal maximal standard uptake value (SUVmax) was determined. Nodal failures were registered to planning scans and related to boosted nodes and treated volume. Relation between SUVmax and nodal control as well as the pattern of regional nodal failure were analyzed. RESULTS: Eighty-four patients were node positive. Nine patients had all metastatic nodes surgically removed. Seventy-five patients had 209 nodes boosted with EBRT. Median nodal boost dose was 62 Gy EQD2 (53-69 Gy EQD2). Median SUVmax was 6 (2-22). No patients had persistent nodal disease, but six patients recurred in a boosted node. SUVmax was significantly higher in nodes that recurred (p = 0.02). However, there was no correlation to nodal dose or volume. Twenty-one patients had a nodal failure including para-aortic nodal (PAN) metastases above the irradiated volume. Nine patients had a PAN-only failure. Patients receiving ≤ 4 cycles of weekly cisplatin had higher risk of nodal failure (p < 0.01). CONCLUSION: Current RT practice provides a high level of control in both boosted nodes and the elective irradiated regional target. However, a high nodal SUVmax is a negative prognostic predictor for nodal control. Attention should be raised to administration of a complete schedule of concurrent chemotherapy as well as treatment of para-aortic nodes.
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Braquiterapia , Carcinoma de Células Escamosas/secundário , Carcinoma de Células Escamosas/terapia , Linfonodos/efeitos da radiação , Recidiva Local de Neoplasia , Radioterapia de Intensidade Modulada , Neoplasias do Colo do Útero/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/uso terapêutico , Aorta , Cisplatino/uso terapêutico , Feminino , Fluordesoxiglucose F18 , Seguimentos , Humanos , Linfonodos/diagnóstico por imagem , Linfonodos/cirurgia , Metástase Linfática , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/diagnóstico , Pelve , Tomografia por Emissão de Pósitrons , Compostos Radiofarmacêuticos , Dosagem Radioterapêutica , Tomografia Computadorizada por Raios X , Falha de Tratamento , Neoplasias do Colo do Útero/patologia , Adulto JovemRESUMO
CONTEXT: Fibroblast growth factor (FGF) 21 acts as a metabolic regulator and its therapeutic use is under investigation. FGF21 signaling requires binding to surface receptors, FGFR1c and ß-klotho. FGF21 resistance is observed in metabolic diseases and FGF21 signaling is regulated by fibroblast activation protein (FAP). Metformin is reported to influence expression and secretion of FGF21 in preclinical models, but the effect of metformin on FGF21 in a clinical trial remains unknown. OBJECTIVE: To investigate how 12 weeks of treatment with metformin affects the FGF21 signaling pathway in patients with type 2 diabetes (T2D). METHODS: Randomized, placebo-controlled study in patients with T2D (n = 24) receiving either metformin (1000 mg twice daily) or placebo. A control group of body mass index- and age-matched healthy individuals (n = 12) received a similar dose of metformin. Blood samples and muscle and fat biopsies were collected at study entry and after 12 weeks. METHODS: Plasma levels of FGF21 (total and intact) and FAP (total and activity) were measured. Muscle and fat biopsies were analyzed for mRNA and protein expression of targets relevant for activation of the FGF21 signaling pathway. RESULTS: Circulating FAP activity decreased after metformin treatment compared with placebo (P = .006), whereas FGF21 levels were unchanged. Metformin treatment increased gene and protein expression of ß-klotho, FGFR1c, and pFGFR1c in adipose tissue. FGF21 mRNA expression increased in muscle tissue after metformin and the FGF21 protein, but not mRNA levels, were observed in adipose tissue. CONCLUSION: Our findings suggest that metformin suppresses the circulating FAP activity and upregulates the expression of FGFR1c and ß-klotho for increased FGF21 signaling in adipose tissue, thus improving peripheral FGF21 sensitivity.
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Diabetes Mellitus Tipo 2 , Metformina , Humanos , Metformina/farmacologia , Metformina/uso terapêutico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Fatores de Crescimento de Fibroblastos , Transdução de Sinais , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , RNA MensageiroRESUMO
BACKGROUND: The number of unexpected focal [18F]FDG-avid findings (incidentalomas) within the parotid gland (PGI) continues to increase with the expanding use of PET/CT scanning. The prevalence of malignancy in PGIs is uncertain and appropriate management is unsettled. AIMS: We aimed to explore the underlying pathologies associated with PGI. MATERIALS AND METHODS: A retrospective review of all patients with parotid gland incidentaloma(s) treated at the Ear-Nose-Throat Department, Aarhus University Hospital, Denmark in the period 2012-2021, was performed. RESULTS: In total, 94 patients with one (n = 86) or two (n = 8) PGI(s) were included. In patients with one PGI, 72 (84%) focuses were benign, two (2%) focuses were malignant (both malignant melanoma metastases), and 12 (14%) focuses were undiagnosed. In patients with two PGIs, all 12 lesions with pathological examinations were benign (4 PGIs were undiagnosed). The median SUVmax found in benign lesions was higher (12.0) compared to malignant lesions (5.5) (p = .043). CONCLUSIONS AND SIGNIFICANCE: The prevalence of malignancy was low (2/94, 2.4%) in PGIs. Based on our findings, PGI in patients without a history of parotid malignancy, who undergo PET/CT scanning for reasons other than head and neck cancer (including malignant melanoma), may be managed similarly to patients with asymptomatic parotid gland tumors.
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Fluordesoxiglucose F18 , Achados Incidentais , Neoplasias Parotídeas , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Humanos , Estudos Retrospectivos , Feminino , Masculino , Pessoa de Meia-Idade , Idoso , Neoplasias Parotídeas/diagnóstico por imagem , Neoplasias Parotídeas/patologia , Adulto , Idoso de 80 Anos ou mais , Compostos Radiofarmacêuticos , Glândula Parótida/diagnóstico por imagem , Glândula Parótida/patologia , Dinamarca/epidemiologiaRESUMO
A ketogenic diet (KD) can induce weight loss and improve glycemic regulation, potentially reducing the risk of developing type 2 diabetes. To elucidate the underlying mechanisms behind these beneficial effects of a KD, we investigated the impact of a KD on organ-specific insulin sensitivity (IS) in skeletal muscle, liver, and adipose tissue. We hypothesized that a KD would increase IS in skeletal muscle. The study included 11 individuals with obesity who underwent a randomized, crossover trial with two three-week interventions: 1) KD and 2) standard diet. Skeletal muscle IS was quantified as the increase in glucose disposal during a hyperinsulinemic-euglycemic clamp (HEC). Hepatic IS and adipose tissue IS were quantified as the relative suppression of endogenous glucose production (EGP) and the relative suppression of palmitate flux during the HEC. The KD led to a 2.2 kg weight loss, increased insulin-stimulated glucose disposal, whereas the relative suppression of EGP during the HEC was similar. In addition, the KD decreased insulin-mediated suppression of lipolysis. In conclusion, a KD increased skeletal muscle IS in individuals with obesity.
RESUMO
AIMS: Myocardial perfusion imaging (MPI) using [15O]H2O positron emission tomography (PET) is used to guide the selection of patients with angina for invasive angiography and possible revascularization. Our study evaluated (i) whether atrial fibrillation (AF) reduces global hyperaemic myocardial blood flow (MBF) and (ii) whether [15O]H2O PET MPI effectively guides revascularization procedures for patients with ongoing AF. METHODS AND RESULTS: We prospectively recruited 346 patients with angina and persistent or paroxysmal AF referred for baseline/hyperaemic [15O]H2O PET MPI. The primary outcome was revascularization within 3 months of MPI. In the analyses, patients were divided into four groups based on whether they had ongoing AF or sinus rhythm (SR) and whether they had previously documented coronary artery disease (CAD) or not. Thus, four groups were compared: SR-noCAD, AF-noCAD, SR-CAD, and AF-CAD. Hyperaemic MBF was affected by both ongoing AF and prior CAD [MBF (mL/min/g): 2.82 (SR-noCAD) vs. 2.12 (AF-noCAD) vs. 2.22 (SR-CAD) vs. 1.80 (AF-CAD), two-way analysis of variance P < 0.0001]. In multiple linear regression, ongoing AF was independently associated with reduced hyperaemic MBF. Every 0.1â mL/min/g decrease in hyperaemic MBF was associated with a 23% increase in odds of early revascularization. Receiver operating characteristic (ROC) analysis of vessel-specific hyperaemic MBF to predict early revascularization yielded the following areas under the ROC curve: SR-noCAD: 0.95 (P < 0.0001); AF-noCAD: 0.79 (P < 0.0001); SR-CAD: 0.78 (P < 0.0001); and AF-CAD: 0.88 (P < 0.0001). CONCLUSION: Ongoing AF is associated with 19-25% reduced global hyperaemic MBF as measured by [15O]H2O MPI PET. Regardless, vessel-specific hyperaemic MBF still predicts early revascularization in patients with AF.
Assuntos
Fibrilação Atrial , Imagem de Perfusão do Miocárdio , Revascularização Miocárdica , Radioisótopos de Oxigênio , Tomografia por Emissão de Pósitrons , Humanos , Fibrilação Atrial/diagnóstico por imagem , Fibrilação Atrial/cirurgia , Feminino , Masculino , Imagem de Perfusão do Miocárdio/métodos , Estudos Prospectivos , Tomografia por Emissão de Pósitrons/métodos , Pessoa de Meia-Idade , Idoso , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/cirurgia , Doença da Artéria Coronariana/complicações , Angina Pectoris/diagnóstico por imagem , Estudos de Coortes , Angiografia Coronária/métodos , Curva ROC , Índice de Gravidade de Doença , Medição de RiscoRESUMO
Introduction: Elite breath-hold divers (BHD) enduring apneas of more than 5 min are characterized by tolerance to arterial blood oxygen levels of 4.3 kPa and low oxygen-consumption in their hearts and skeletal muscles, similar to adult seals. Adult seals possess an adaptive higher hemoglobin-concentration and Bohr effect than pups, and when sedated, adult seals demonstrate a blood shift from the spleen towards the brain, lungs, and heart during apnea. We hypothesized these observations to be similar in human BHD. Therefore, we measured hemoglobin- and 2,3-biphosphoglycerate-concentrations in BHD (n = 11) and matched controls (n = 11) at rest, while myocardial mass, spleen and lower extremity volumes were assessed at rest and during apnea in BHD. Methods and results: After 4 min of apnea, left ventricular myocardial mass (LVMM) determined by 15O-H2O-PET/CT (n = 6) and cardiac MRI (n = 6), was unaltered compared to rest. During maximum apnea (â¼6 min), lower extremity volume assessed by DXA-scan revealed a â¼268 mL decrease, and spleen volume, assessed by ultrasonography, decreased â¼102 mL. Compared to age, BMI and VO2max matched controls (n = 11), BHD had similar spleen sizes and 2,3- biphosphoglycerate-concentrations, but higher total hemoglobin-concentrations. Conclusion: Our results indicate: 1) Apnea training in BHD may increase hemoglobin concentration as an oxygen conserving adaptation similar to adult diving mammals. 2) The blood shift during dry apnea in BHD is 162% more from the lower extremities than from the spleen. 3) In contrast to the previous theory of the blood shift demonstrated in sedated adult seals, blood shift is not towards the heart during dry apnea in humans.