Intense 68 Ga-OncoFAP Uptake as a New Promising Diagnostic Biomarker in Cardiac Sarcoidosis.

ABSTRACT: A 72-year-old man revealed typical findings of cardiac sarcoidosis on cardiovascular MRI. However, 18 F-FDG PET showed no hypermetabolism. Therefore, immunosuppression was not initiated. After 2 years, ventricular arrhythmias and heart failure worsened. 68 Ga-fibroblast activation protein inhibitor PET was initiated to evaluate potential adverse remodeling due to progressive myocardial fibrosis. A second 18 F-FDG PET still revealed no hypermetabolism, and the patient received an implanted cardioverter defibrillator after electrophysiological risk stratification. We present a case of intense fibroblast activation despite a missing 18 F-FDG uptake (mismatch).

Cardiac Sarcoidosis-Diagnostic and Therapeutic Challenges.

Sarcoidosis is a multisystem disorder of unknown etiology. The leading hypothesis involves an antigen-triggered dysregulated T-cell-driven immunologic response leading to non-necrotic granulomas. In cardiac sarcoidosis (CS), the inflammatory response can lead to fibrosis, culminating in clinical manifestations such as atrioventricular block and ventricular arrhythmias. Cardiac manifestations frequently present as first and isolated signs or may appear in conjunction with extracardiac manifestations. The incidence of sudden cardiac death (SCD) is high. Diagnosis remains a challenge. For a definite diagnosis, endomyocardial biopsy (EMB) is suggested. In clinical practice, compatible findings in advanced imaging using cardiovascular magnetic resonance (CMR) and/or positron emission tomography (PET) in combination with extracardiac histological proof is considered sufficient. Management revolves around the control of myocardial inflammation by employing immunosuppression. However, data regarding efficacy are merely based on observational evidence. Prevention of SCD is of particular importance and several guidelines provide recommendations regarding device therapy. In patients with manifest CS, outcome data indicate a 5-year survival of around 90% and a 10-year survival in the range of 80%. Data for patients with silent CS are conflicting; some studies suggest an overall benign course of disease while others reported contrasting observations. Future research challenges involve better understanding of the immunologic pathogenesis of the disease for a targeted therapy, improving imaging to aid early diagnosis, assessing the need for screening of asymptomatic patients and randomized trials.

Radiomics-Based Prediction Model for Outcome of Radioembolization in Metastatic Colorectal Cancer.

PURPOSE: To evaluate the benefit of a contrast-enhanced computed tomography (CT) radiomics-based model for predicting response and survival in patients with colorectal liver metastases treated with transarterial Yttrium-90 radioembolization (TARE). MATERIALS AND METHODS: Fifty-one patients who underwent TARE were included in this single-center retrospective study. Response to treatment was assessed using the Response Evaluation Criteria in Solid Tumors (RECIST 1.1) at 3-month follow-up. Patients were stratified as responders (complete/partial response and stable disease, n = 24) or non-responders (progressive disease, n = 27). Radiomic features (RF) were extracted from pre-TARE CT after segmentation of the liver tumor volume. A model was built based on a radiomic signature consisting of reliable RFs that allowed classification of response using multivariate logistic regression. Patients were assigned to high- or low-risk groups for disease progression after TARE according to a cutoff defined in the model. Kaplan-Meier analysis was performed to analyze survival between high- and low-risk groups. RESULTS: Two independent RF [Energy, Maximal Correlation Coefficient (MCC)], reflecting tumor heterogeneity, discriminated well between responders and non-responders. In particular, patients with higher magnitude of voxel values in an image (Energy), and texture complexity (MCC), were more likely to fail TARE. For predicting treatment response, the area under the receiver operating characteristic curve of the radiomics-based model was 0.75 (95% CI 0.48-1). The high-risk group had a shorter overall survival than the low-risk group (3.4 vs. 6.4 months, p < 0.001). CONCLUSION: Our CT radiomics model may predict the response and survival outcome by quantifying tumor heterogeneity in patients treated with TARE for colorectal liver metastases.

Diagnostic Performance of [18F]TFB PET/CT Compared with Therapeutic Activity [131I]Iodine SPECT/CT and [18F]FDG PET/CT in Recurrent Differentiated Thyroid Carcinoma.

[18F]tetrafluoroborate ([18F]TFB) is an emerging PET tracer with excellent properties for human sodium iodide symporter (NIS)-based imaging in patients with differentiated thyroid cancer (DTC). The aim of this study was to compare [18F]TFB PET with high-activity posttherapeutic [131I]iodine whole-body scintigraphy and SPECT/CT in recurrent DTC and with [18F]FDG PET/CT in suspected dedifferentiation. Methods: Twenty-six patients treated with high-activity radioactive [131I]iodine therapy (range, 5.00-10.23 GBq) between May 2020 and November 2022 were retrospectively included. Thyroid-stimulating hormone was stimulated by 2 injections of recombinant thyroid-stimulating hormone (0.9 mg) 48 and 24 h before therapy. Before treatment, all patients underwent [18F]TFB PET/CT 40 min after injection of a median of 321 MBq of [18F]TFB. To study tracer kinetics in DTC lesions, 23 patients received an additional scan at 90 min. [131I]iodine therapeutic whole-body scintigraphy and SPECT/CT were performed at a median of 3.8 d after treatment. Twenty-five patients underwent additional [18F]FDG PET. Two experienced nuclear medicine physicians evaluated all imaging modalities in consensus. Results: A total of 62 suspected lesions were identified; of these, 30 lesions were [131I]iodine positive, 32 lesions were [18F]TFB positive, and 52 were [18F]FDG positive. Three of the 30 [131I]iodine-positive lesions were retrospectively rated as false-positive iodide uptake. Tumor-to-background ratio measurements at the 40- and 90-min time points were closely correlated (e.g., for the tumor-to-background ratio for muscle, the Pearson correlation coefficient was 0.91; P < 0.001; n = 49). We found a significant negative correlation between [18F]TFB uptake and [18F]FDG uptake as a potential marker for dedifferentiation (Pearson correlation coefficient, -0.26; P = 0.041; n = 62). Conclusion: Pretherapeutic [18F]TFB PET/CT may help to predict the positivity of recurrent DTC lesions on [131I]iodine scans. Therefore, it may help in the selection of patients for [131I]iodine therapy. Future prospective trials for iodine therapy guidance are warranted. Lesion [18F]TFB uptake seems to be inversely correlated with [18F]FDG uptake and therefore might serve as a dedifferentiation marker in DTC.

177 Lu-DOTATATE (Lutathera) Therapy in 68 Ga-DOTATATE PET/CT-Negative Liver Metastases of a Neuroendocrine Tumor.

ABSTRACT: A 73-year-old man with metastatic pancreatic neuroendocrine tumor was evaluated with 68 Ga-DOTATATE PET/CT for peptide receptor radionuclide therapy. Both PET-positive and negative lesions were seen in the liver, along with extrahepatic metastases. Histopathology was obtained from one of the PET-negative liver lesions to exclude secondary malignancy. Histology confirmed a well-differentiated (G2) metastasis of pNET with high somatostatin receptor expression. We initiated peptide receptor radionuclide therapy with close monitoring of the PET-negative liver metastases. We present a rare case, where posttherapeutic scintigraphy revealed vigorous uptake of 177 Lu-DOTATATE even in the 68 Ga-DOTATATE PET-negative liver metastases. Follow-up PET/CT showed a partial response to therapy.

Radiomics of Tumor Heterogeneity in 18F-FDG-PET-CT for Predicting Response to Immune Checkpoint Inhibition in Therapy-Naïve Patients with Advanced Non-Small-Cell Lung Cancer.

We aimed to evaluate the predictive and prognostic value of baseline 18F-FDG-PET-CT (PET-CT) radiomic features (RFs) for immune checkpoint-inhibitor (CKI)-based first-line therapy in advanced non-small-cell lung cancer (NSCLC) patients. In this retrospective study 44 patients were included. Patients were treated with either CKI-monotherapy or combined CKI-based immunotherapy-chemotherapy as first-line treatment. Treatment response was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST). After a median follow-up of 6.4 months patients were stratified into "responder" (n = 33) and "non-responder" (n = 11). RFs were extracted from baseline PET and CT data after segmenting PET-positive tumor volume of all lesions. A Radiomics-based model was developed based on a Radiomics signature consisting of reliable RFs that allow classification of response and overall progression using multivariate logistic regression. These RF were additionally tested for their prognostic value in all patients by applying a model-derived threshold. Two independent PET-based RFs differentiated well between responders and non-responders. For predicting response, the area under the curve (AUC) was 0.69 for "PET-Skewness" and 0.75 predicting overall progression for "PET-Median". In terms of progression-free survival analysis, patients with a lower value of PET-Skewness (threshold < 0.2014; hazard ratio (HR) 0.17, 95% CI 0.06-0.46; p < 0.001) and higher value of PET-Median (threshold > 0.5233; HR 0.23, 95% CI 0.11-0.49; p < 0.001) had a significantly lower probability of disease progression or death. Our Radiomics-based model might be able to predict response in advanced NSCLC patients treated with CKI-based first-line therapy.

Smartphone addiction and life satisfaction: mediating effect of negative emotions / Adicción a teléfonos inteligentes y satisfacción con la vida: efecto mediador de las emociones negativas

Background: Smartphone users have increased worldwide, due to their multifunctionality and accessibility. Objective: To determine the mediating effect of negative emotions between life satisfaction and smartphone addiction in college students. Method: A structural equation explanatory model was proposed in which each negative emotion (depression, anxiety, and stress) has a mediating role between life satisfaction and cell phone addiction. To this end, 1109 university students from Metropolitan Lima were selected and administered the DASS 21, SABAS, SWLS. Result: A partial effect of each mediating model was found, in addition to Satisfaction with life achieved a direct effect on cell phone addiction; at the same time the mediating variables achieved a significant direct effect on addictive behavior. Conclusion: Negative emotions have a mediating role in explaining smartphone addiction.

Introducción: Los usuarios de teléfonos inteligentes se han incrementado a nivel mundial, debido a su multifuncionalidad y accesibilidad. Objetivo: Determinar el efecto mediador de las emociones negativas entre la satisfacción con la vida y la adicción a los teléfonos inteligentes en universitarios. Método: Se planteó un modelo explicativo de ecuaciones estructurales en el cual cada emoción negativa (depresión, ansiedad y estrés) tienen un rol mediador entre la satisfacción con la vida y la adicción a los celulares. Con tal fin, se seleccionaron 1109 universitarios de Lima Metropolitana a los cuales se les aplicaron el DASS 21, SABAS, SWLS. Resultados: Se encontró un efecto parcial de cada modelo mediador, además la Satisfacción con la vida logró un efecto directo sobre la adicción a los teléfonos celulares; al mismo tiempo las variables mediadoras consiguieron un efecto directo significativo sobre la conducta adictiva. Conclusión: las emociones negativas tienen un rol mediador en la explicación de la adicción a los teléfonos inteligentes.

Alpha-1 Antitrypsin Deficiency: Principles of Care.

Alpha-1 antitrypsin deficiency is an autosomal co-dominant inherited disorder that results in decreased circulating levels of alpha-1 antitrypsin (also known as alpha-1 proteinase inhibitor) and predisposes affected individuals to early onset lung and liver disease. There is currently no cure for alpha-1 antitrypsin deficiency. However, appropriate treatment and a high standard of clinical care can prevent patients from being seriously affected and having to undergo major medical interventions, such as organ transplantation. Beyond managing the symptoms associated with alpha-1 antitrypsin deficiency, alpha-1 proteinase inhibitor therapy is the only treatment for the condition's underlying cause. Early diagnosis is important to ensure efficient therapeutic strategies and to minimize further deterioration of lung function. alpha-1 antitrypsin deficiency is under diagnosed globally, partly because the disease has no unique presenting symptoms. This document was prepared by a Portuguese multidisciplinary group and it aims to set out comprehensive principles of care for Alpha-1 antitrypsin deficiency. These include the importance of registries, the need for clinical research, the need for consistent recommendations (regarding diagnosis, treatment and monitoring), the role of reference centres, the requirement for sustained access to treatment, diagnostic and support services, and the role of patient organizations.

A deficiência de alfa-1 antitripsina é uma doença hereditária autossómica co-dominante que resulta numa diminuição dos níveis plasmáticos de alfa-1 antitripsina (também conhecida por inibidor da alfa-1 proteinase) e predispõe os indivíduos afetados ao desenvolvimento de doença pulmonar e hepática precoce. Atualmente não existe cura para a deficiência de alfa-1 antitripsina. No entanto, o tratamento adequado e um elevado padrão de cuidados clínicos podem prevenir que os doentes sejam gravemente afetados e terem que se submeter a intervenções médicas major, como o transplante de órgão. Para além de atuar nos sintomas associados à deficiência de alfa-1 antitripsina, a terapêutica com o inibidor da alfa-1 proteinase é o único tratamento disponível que atua na causa subjacente desta patologia. O diagnostico precoce é importante para assegurar a implementação de estratégias terapêuticas eficientes e para minimizar a destruição adicional da função pulmonar. A deficiência de alfa-1 antitripsina está globalmente sub diagnosticada, em parte devido ao fato desta doença não apresentar sintomas únicos. Este documento foi preparado por um grupo multidisciplinar e visa estabelecer princípios de cuidados abrangentes para a deficiência de alfa-1 antitripsina. Estes incluem a importância dos registros, a necessidade de investigação clinica, a necessidade de recomendações consistentes (no que diz respeito ao diagnostico, tratamento e monitorização), o papel dos centros de referência, a necessidade de acesso sustentado ao tratamento, diagnostico e serviços de suporte, e o papel das associações de doentes.

The role of emotionality in the acquisition of new concrete and abstract words.

A processing advantage for emotional words relative to neutral words has been widely demonstrated in the monolingual domain (e.g., Kuperman et al., 2014). It is also well-known that, in bilingual speakers who have a certain degree of proficiency in their second language, the effects of the affective content of words on cognition are not restricted to the native language (e.g., Ferré et al., 2010). The aim of the present study was to test whether this facilitatory effect can also be obtained during the very early stages of word acquisition. In the context of a novel word learning paradigm, participants were trained on a set of Basque words by associating them to their Spanish translations. Words' concreteness and affective valence were orthogonally manipulated. Immediately after the learning phase and 1 week later, participants were tested in a Basque go-no go lexical decision task as well as in a translation task in which they had to provide the Spanish translation of the Basque words. A similar pattern of results was found across tasks and sessions, revealing main effects of concreteness and emotional content as well as an interaction between both factors. Thus, the emotional content facilitated the acquisition of abstract, but not concrete words, in the new language, with a more reliable effect for negative words than for positive ones. The results are discussed in light of the embodied theoretical view of semantic representation proposed by Kousta et al. (2011).