Search Results (98)

Poorly differentiated thyroid malignancy, a rare histological type of aggressive thyroid malignancy with associated difficulties and gaps in its histological and molecular characterization, might lead to challenging clinical presentations that require a prompt multimodal approach. This case study involved a 56-year-old, non-smoking male with a rapidly developing goiter (within 2–3 months) in association with mild, non-specific neck compressive symptoms. His medical history was irrelevant. A voluminous goiter with substernal and posterior extension up to the vertebral bodies was detected using an ultrasound and computed tomography (CT) scan and required emergency thyroidectomy. He had normal thyroid function, as well as negative thyroid autoimmunity and serum calcitonin. The surgery was successful upon “Y” incision, which was used to give better access to the retrosternal component in order to avoid a sternotomy. Post-operatively, the subject developed hypoparathyroidism-related hypocalcemia and showed a very high serum thyroglobulin level (>550 ng/mL). The pathological report confirmed poorly differentiated, multifocal thyroid carcinoma (with an insular, solid, and trabecular pattern) against a background of papillary carcinoma (pT3b, pN0, and pM1; L1; V2; Pn0; R1; and stage IVB). The subject received 200 mCi of radioiodine therapy for 6 weeks following the thoracic surgery. Whole-body scintigraphy was performed before radioiodine therapy and showed increased radiotracer uptake at the thyroid remnants and pre-tracheal levels. Additionally, single-photon emission computed tomography combined with CT (SPECT/CT) was performed, and confirmed the areas of intense uptake, in addition to a moderate uptake in the right and left pulmonary parenchyma, suggesting lung metastasis. To conclude, an overall low level of statistical evidence exists regarding poorly differentiated malignancy in substernal goiters, and the data also remains scarce regarding the impact of genetic and molecular configurations, such as the BRAF-positive profile, in this specific instance. Furthermore, multimodal management includes additional diagnosis methods such as SPECT/CT, while long-term multilayered therapy includes tyrosine kinase inhibitors if the outcome shows an iodine-resistant profile with a poor prognosis. Awareness remains a key factor in cases of a poorly differentiated carcinoma presenting as a rapidly growing goiter with substernal extension in an apparently healthy adult. A surgical approach, while varying with the surgeon’s skills, represents a mandatory step to ensure a better prognosis. In addition to a meticulous histological characterization, genetic/molecular features provide valuable information regarding the outcome and can further help with the decision to use new anti-cancer drugs if tumor response upon radioiodine therapy is no longer achieved; such a development is expected in this disease stage in association with a BRAF-positive configuration. Full article

Background/Objectives: Gastrin-releasing peptide receptor (GRPR) is overexpressed in breast cancer and might be used as a theranostics target. The expression of GRPR strongly correlates with estrogen receptor (ER) expression. Visualization of GRPR-expressing breast tumors might help to select the optimal treatment. Developing GRPR-specific probes for SPECT would permit imaging-guided therapy in regions with restricted access to PET facilities. In this first-in-human study, we evaluated the safety, biodistribution, and dosimetry of the [^99mTc]Tc-DB8 GRPR-antagonistic peptide. We also addressed the important issue of finding the optimal injected peptide mass. Methods: Fifteen female patients with ER-positive primary breast cancer were enrolled and divided into three cohorts receiving [^99mTc]Tc-DB8 (corresponding to three distinct doses of 40, 80, or 120 µg DB8) comprising five patients each. Additionally, four patients with ER-negative primary tumors were injected with 80 µg [^99mTc]Tc-DB8. The injected activity was 360 ± 70 MBq. Planar scintigraphy was performed after 2, 4, 6, and 24 h, and SPECT/CT scans followed planar imaging 2, 4, and 6 h after injection. Results: No adverse events were associated with [^99mTc]Tc-DB8 injections. The effective dose was 0.009–0.014 mSv/MBq. Primary tumors and all known lymph node metastases were visualized irrespective of injected peptide mass. The highest uptake in the ER-positive tumors was 2 h after injection of [^99mTc]Tc-DB8 at a 80 µg DB8 dose (SUV_max 5.3 ± 1.2). Injection of [^99mTc]Tc-DB8 with 80 µg DB8 provided significantly (p < 0.01) higher uptake in primary ER-positive breast cancer lesions than injection with 40 µg DB8 (SUV_max 2.0 ± 0.3) or 120 µg (SUV_max 3.2 ± 1.4). Tumor-to-contralateral breast ratio after injection of 80 μg was also significantly (p < 0.01, ANOVA test) higher than ratios after injection of other peptide masses. The uptake in ER-negative lesions was significantly lower (SUV_max 2.0 ± 0.3) than in ER-positive tumors. Conclusions: Imaging using [^99mTc]Tc-DB8 is safe, tolerable, and associated with low absorbed doses. The tumor uptake is dependent on the injected peptide mass. The injection of an optimal mass (80 µg) provides the highest uptake in ER-positive tumors. At optimal dosing, the uptake was significantly higher in ER-positive than in ER-negative lesions. Full article

Background/Objectives: Red bone marrow irradiation is a major concern for patients with advanced prostate cancer undergoing [¹⁷⁷Lu]Lu-PSMA therapy. However, low uptake in the red bone marrow and the presence of bone lesions complicate image-based red bone marrow dosimetry. This study aimed to investigate the general feasibility of image-based red bone marrow activity estimation for [¹⁷⁷Lu]Lu-PSMA treatment and to develop a fully automated workflow for clinical implementation. Methods: In the first part of the study, 175 virtual patient phantoms with realistic ¹⁷⁷Lu activity distributions were generated based on 639 pre-therapeutic [¹⁸F]F-PSMA-1007 PET/CT scans. The SIMIND Monte Carlo tool was used to simulate the ¹⁷⁷Lu SPECT acquisitions (24 h post-injection (p.i.)), which were used to assess the uncertainty of red bone marrow activity estimation. In the second part, red bone marrow self- and cross-absorbed doses were estimated for four therapy cycles of 20 patients. Results: The simulation study shows a significant overestimation of activity in skeletal sites with bone lesions, with median recovery coefficients (RCs) across all phantoms yielding a median of 225% (range: 106–1015%). In contrast, the median RCs were markedly lower in skeletal sites neighboring or distant to lesion-carrying sites (105% [72–163%] and 107% [77–130%], respectively). The median total absorbed dose to the red bone marrow was 20.8 mGy/GBq (range: 5.6–297.9 mGy/GBq). Median blood levels decreased with an increasing median cumulative total absorbed dose. Conclusions: Reliable estimation of activity concentration in skeletal sites without bone lesion infiltration has been shown to be feasible. Based on this finding, an automated workflow for routine image-based red bone marrow dosimetry was developed. Full article

A 49-year-old female presented for nuclear medicine diagnostics of a sonographically suspected parathyroid adenoma dorsal to the cranial pole of the right thyroid lobe. The patient received Tc-99m-pertechnetate and Tc-99m-sestamibi (including SPECT/CT) scans, revealing no sestamibi uptake by the suspected parathyroid adenoma but a ventrally adjacent autonomous thyroid adenoma. Additional F-18-ethylcholine-PET/CT as well as subsequent Tc-99m-sestamibi-SPECT/US and F-18-ethylcholine-PET/US fusion imaging confirmed the suspected diagnosis of simultaneous autonomous thyroid adenoma and parathyroid adenoma. A blood analysis showed additional Graves’ disease. Full article

Background and Objectives: Single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) is a well-established technique for evaluating myocardial perfusion and function in patients with suspected or known coronary artery disease. While conventional dual-detector SPECT scanners have limitations in spatial resolution and photon detection sensitivity, recent advancements, including full-ring solid-state cadmium zinc telluride (CZT) detectors, offer enhanced image quality and improved diagnostic accuracy. This study aimed to compare the performance of Veriton-CT, a full-ring CZT SPECT system, with GE Discovery 530c, a dedicated cardiac fixed-angle gamma camera, in myocardial perfusion imaging and their correlation with coronary angiography findings. Materials and Methods: This was a prospective study that analyzed 21 patients who underwent MPI at the Department of Nuclear Medicine, Lithuanian University of Health Sciences, Kauno Klinikos. A one-day stress–rest protocol using 99mTc-Sestamibi was employed, with stress testing performed via bicycle ergometry or pharmacological induction. MPI was first conducted using GE Discovery 530c (GE Health Care, Boston, MA, USA), followed by imaging on Veriton-CT, which included low-dose CT for attenuation correction. The summed stress score (SSS), summed rest score (SRS), and summed difference score (SDS) were analyzed and compared between both imaging modalities. Coronary angiography results were retrospectively collected, and lesion-based analysis was performed to assess the correlation between imaging results and the presence of significant coronary artery stenosis (≥35% and ≥70% narrowing). Image quality and the certainty of distinguishing the inferior myocardial wall from extracardiac structures were also evaluated by two independent researchers with differing levels of experience. Results: Among the 14 patients included in the final analysis, Veriton-CT was more likely to classify MPI scans as normal (64.3%) compared to GE Discovery 530c (28.6%). Additionally, Veriton-CT provided a better assessment of the right coronary artery (RCA) basin, showing greater agreement with coronary angiography findings than GE Discovery 530c, although the difference was not statistically significant. No significant differences in lesion overlap were observed for the left anterior descending artery (LAD) or left circumflex artery (LCx) basins. Furthermore, the image quality assessment revealed slightly better delineation of extracardiac structures using Veriton-CT (Spectrum Dynamics Medical, Caesarea, Israel), particularly when evaluated by an experienced researcher. However, no significant difference was observed when assessed by a less experienced observer. Conclusions: Our findings suggest that Veriton-CT, with its full-ring CZT detector system, may offer advantages over fixed-angle gamma cameras in improving image quality and reducing attenuation artifacts in MPI. Although the difference in correlations with coronary angiography findings was not statistically significant, Veriton-CT showed a trend toward better agreement, particularly in the RCA basin. These results indicate that full-ring SPECT imaging could improve the diagnostic accuracy of non-invasive MPI, potentially reducing the need for unnecessary invasive angiography. Further studies with larger patient cohorts are required to confirm these findings and evaluate the clinical impact of full-ring SPECT technology in myocardial perfusion imaging. Full article

Coronary artery disease remains the leading cause of morbidity and mortality worldwide. With the changing clinical manifestation and novel therapeutical options, precise disease phenotyping becomes increasingly important at the point of care. In the management of coronary artery disease, myocardial perfusion imaging (MPI) remains the cornerstone of clinical practice. Although traditionally MPI has been primarily performed with single photon emission computed tomography (SPECT), nowadays, given the changing spectrum of the disease, greater precision and additional assessment of myocardial blood flow are desired. Due to the fundamental advantages of PET over SPECT, i.e., higher spatial resolution, accurate attenuation correction for each scan, and higher count rates, the sensitivity and specificity of PET MPI are higher than those of SPECT MPI and are estimated to be approximately 90–92% vs. 83–88% and 81–87% vs. 70–76%, respectively, according to meta-analysis data. Consequently, over the past decade, we have witnessed an increased uptake of positron emission tomography (PET) MPI. With the improved spatial resolution, the ability to quantify myocardial blood flow, and the potential to depict the burden of coronary atherosclerosis with low-dose computed tomography, PET/CT is uniquely positioned to facilitate a comprehensive non-invasive assessment of disease, providing an opportunity for precision medicine. The wealth of data obtained during a single imaging session can be challenging to integrate at the time of image analysis. There has therefore been an increasing interest in developing predefined thresholds or variables (scores) which combine the multidimensional data acquired with PET MPI. Beyond MPI, PET can also serve for the assessment of disease activity at the atherosclerotic plaque level, further refining our understanding of the biology of coronary artery disease and providing hope for enhanced prediction of myocardial infarctions. In this narrative review, we present the current applications of PET MPI in coronary artery disease and focus specifically on two areas that have recently garnered considerable interest—the integration of multiparametric PET MPI data and coronary plaque activity PET imaging. Full article

Introduction: The highly contagious 2019 novel coronavirus that causes coronavirus disease 2019 increased the scientific community’s interest in diagnosing and monitoring COVID-19. Due to the findings about the association between COVID-19 infection and pulmonary disturbances, the need for the use of complementary tests that can be carried out, preserving the health of patients, has grown. In this context, single-photon emission computed tomography (SPECT) was performed during the COVID-19 pandemic to assess and try to diagnose lung lesions. The aim of this current review was to investigate the types of SPECT images most commonly used and the main pulmonary parenchymal lesions and different lung perfusion abnormalities observed in these images in individuals with COVID-19 in different countries in the world. Materials and Methods: Electronic searches in the MEDLINE/PubMed, Embase, Scopus, Web of Science, and CINAHL databases were conducted in December 2022. Studies that used SPECT/CT scans to evaluate pulmonary involvements due to COVID-19, with no language restriction, were included. Two reviewers, who independently examined titles and abstracts, identified records through the database search and reference screening, and irrelevant studies were excluded based on the eligibility criteria. Relevant complete texts were analyzed for eligibility, and all relevant studies were included in a systematic review. Results: Eight studies with regular methodological quality were included. The types of SPECT examinations used in the included articles were SPECT/CT, Q SPECT/CT, and V/Q SPECT. The possible pulmonary complication most observed was pulmonary embolism. Conclusions: This systematic review demonstrated that SPECT/CT scans, mainly with perfusion methods, allow the maximum extraction of benefits from pulmonary images, in safety, suggesting efficiency in the differential diagnosis, including of respiratory diseases of different etiology, and with diagnostics and additional analyses, can possibly aid the development of suitable therapeutic strategies for each patient. Randomized clinical trials and studies of good methodological quality are necessary to confirm the findings of this review and help better understand the types of SPECT images most commonly used and the main pulmonary parenchymal lesions observed in the images in individuals with COVID-19. Full article

Parkinson’s disease (PD) is a neurodegenerative disorder characterized by motor and neuropsychiatric symptoms resulting from the loss of dopamine-producing neurons in the substantia nigra pars compacta (SNc). Dopamine transporter scan (DATSCAN), based on single-photon emission computed tomography (SPECT), is commonly used to evaluate the loss of dopaminergic neurons in the striatum. This study aims to identify a biomarker from DATSCAN images and develop a machine learning (ML) algorithm for PD diagnosis. Using 13 DATSCAN-derived parameters and patient handedness from 1309 individuals in the Parkinson’s Progression Markers Initiative (PPMI) database, we trained an AdaBoost classifier, achieving an accuracy of 98.88% and an area under the receiver operating characteristic (ROC) curve of 99.81%. To ensure interpretability, we applied the local interpretable model-agnostic explainer (LIME), identifying contralateral putamen SBR as the most predictive feature for distinguishing PD from healthy controls. By focusing on a single biomarker, our approach simplifies PD diagnosis, integrates seamlessly into clinical workflows, and provides interpretable, actionable insights. Although DATSCAN has limitations in detecting early-stage PD, our study demonstrates the potential of ML to enhance diagnostic precision, contributing to improved clinical decision-making and patient outcomes. Full article

Background/Objectives: ¹²³Iodo-metaiodobenzylguanidine single photon emission computed tomography/computed tomography (¹²³I-MIBG SPECT/CT) is used to evaluate the cardiac sympathetic nervous system in cardiac diseases such as arrhythmogenic right ventricular cardiomyopathy (ARVC) and α-synucleinopathies such as Parkinson’s diseases. A common feature of these diseases is denervation. We aimed to compare quantitative and semi-quantitative cardiac sympathetic innervation using ¹²³I-MIBG imaging of ARVC and α-synucleinopathies. Methods: Cardiac innervation was assessed using ¹²³I-MIBG SPECT/CT in 20 patients diagnosed with definite ARVC and 8 patients with clinically diagnosed α-synucleinopathies. Heart-to-mediastinum-ratio (H/M-ratio), as semi-quantitative, was evaluated. Additionally, standardized uptake value (SUV), as quantitative, was measured as SUV_median, SUV_max, and SUV_peak in the left ventricle (LV), the right ventricle (RV), and in the global heart, based on a CT scan following quantitative image reconstruction. Results: The quantification of ¹²³I-MIBG uptake in the LV, the RV, and the global heart was feasible in patients suffering from α-synucleinopathies. SUV_median, and SUV_peak demonstrated a significant difference between ARVC and α-synucleinopathies across all regions, with the α-synucleinopathy group showing a lower uptake. In addition, the H/M ratio showed significantly lower uptake in patients with α-synucleinopathies than in patients with ARVC. Conclusions: Patients with α-synucleinopathies demonstrate significantly lower cardiac innervation in semi-quantitative and quantitative examinations than ARVC patients. The comparison of semi-quantitative and quantitative examinations suggests that quantitative examination offers an advantage. Quantitative analysis can be performed separately for the LV, RV, and global heart. However, analyzing the LV or RV does not provide additional benefit over analyzing the global heart in distinguishing between α-synucleinopathies and ARVC. Considering the different clinical manifestations of these two diseases, the absolute SUV values should not be generalized across different pathologies, and disease-specific ranges should be used instead. Full article

Patients diagnosed with multiple endocrine neoplasia type-1 (MEN1) often initially present with primary hyperparathyroidism (pHPT), and typically undergo surgical intervention. While laboratory tests are fundamental for diagnosis, imaging is crucial for localizing pathological parathyroids to aid in precise surgical planning. In this pictorial review, we will begin by comprehensively examining key imaging techniques and their established protocols, evaluating their effectiveness in detecting abnormal parathyroid glands. This analysis will emphasize both the advantages and potential limitations within the clinical context of MEN1 patients. Additionally, we will explore integrated imaging approaches that combine multiple modalities to enhance localization accuracy and optimize surgical planning—an essential component of holistic management in MEN1 cases. Various imaging techniques are employed for presurgical localization, including ultrasound (US), multiphase parathyroid computed tomography (CT) scanning (4D CT), magnetic resonance imaging (MRI), and nuclear medicine techniques like single photon emission computed tomography/CT (SPECT/CT) and positron emission tomography/CT (PET/CT). US is non-invasive, readily available, and provides high spatial resolution. However, it is operator-dependent and may have limitations in certain cases, such as intrathyroidal locations, the presence of bulky goiters, thyroid nodules, and previous thyroidectomy. Four-dimensional CT offers dynamic imaging, aiding in the identification of enlarged parathyroid glands, particularly in cases of ectopic or supernumerary glands. Despite concerns about radiation exposure, efforts are underway to optimize protocols and reduce doses, including the use of dual-energy CT. MR imaging offers excellent soft tissue contrast without radiation exposure, potentially providing superior differentiation between parathyroid glands and the surrounding structures. Radionuclide imaging, especially PET/CT using radiopharmaceuticals like [¹⁸F]FCH, shows promising results in localizing parathyroid tumors, particularly in patients with MEN1. [¹⁸F]FCH PET/CT demonstrates high sensitivity and may provide additional information compared to other imaging modalities, especially in cases of recurrent HPT. Full article

This study evaluated the occupational exposure of radiopharmacists, nurses, radiological technologists, and radiological technologist assistants involved in ^99mTc-MDP bone scintigraphy procedures. Actual occupational effective doses for individual staff needed ascertaining. An environmental radiation exposure audit revealed all nuclear medicine areas were compliant with ICRP and IAEA guidelines. To ascertain individual doses, they were recorded by OSL badges. The highest exposure was to the radiopharmacists, Hp(0.07) 2.19 µSv during radiolabeling. The nurse administering ^99mTc-MDP recorded a dose of 0.27 µSv at Hp(0.07), 26.01% of the total occupational effective dose. The radiological technologist and assistant receive 73.05% of the total effective dose. However, the highest effective dose was received by the technologist assistant positioning patients for SPECT/CT scans, with an effective dose of 32.03 µSv. Single and double dosimetry effective dose estimate algorithms were evaluated, resulting in the double dosimetry being more accurate. The Padovani et al. algorithm was found to most closely align with ^99mTc-MDP actual effective dose values (p > 0.05), thereby validating the measurement methods used in this study. The research offers benchmark environmental exposure and effective doses applicable in audits and the continuous effort to enhance radiation safety for personnel during ^99mTc-MDP bone scintigraphy. Full article

In same-day radioembolization, 99mTc-MAA SPECT/CT, 90Y radioembolization, and post-treatment 90Y SPECT/CT procedures are conducted on the same-day, resulting in a dual-isotope environment of 90Y and 99mTc during post-treatment imaging. This study aimed to quantify the impact of 99mTc on 90Y bremsstrahlung-SPECT/CT image quality and to establish an optimised imaging protocol for both clinical practice, and with advanced reconstruction techniques. Utilising a NEMA IQ phantom, contrast recovery coefficients (CRCs) were measured to evaluate the 90Y image quality degradation caused by 99mTc. SPECT/CT scans of 90Y-only and 90Y with varying amounts of 99mTc were conducted using a standard protocol (90–120 keV energy window, high-energy collimator) and various dual-isotope protocols. The standard protocol resulted in a marked CRC reduction, with the largest sphere’s CRC decreasing from 0.21 (90Y-only) to 0.05 when 99mTc activity was 5% of 90Y. For an optimised protocol (160–200 keV energy window, high-energy collimator) CRC values were 0.16 for 90Y-only and 0.15 for 90Y+99mTc. The highest CRC values were achieved with an advanced Monte Carlo-based reconstruction, showing 0.58 for 90Y-only and 0.46 for 90Y+99mTc. Image quality degradation was noted in dual-isotope settings even when using an optimised protocol. Advanced reconstruction techniques markedly improved post-treatment image quality. Full article

Background/Objectives: Prostate cancer (PC) represents the second most diagnosed form of cancer in men on a global scale. Despite the theranostic efficacy of prostate-specific membrane antigen (PSMA) radioligands, there is a spectrum of PC disease in which PSMA expression is low or absent. The gastrin-releasing peptide receptor (GRPR), also known as the bombesin type 2 receptor, has been identified as a target in both the early and advanced stages of PC. The objective of this study was to prepare and preclinically evaluate [^99mTc]Tc-iPSMA-Bombesin ([^99mTc]Tc-iPSMA-BN), estimate dosimetry in healthy subjects, and assess the diagnostic efficacy of the radiotracer in patients with metastatic PC, with the hypothesis of non-inferiority to one of the gold standards, [¹⁸F]-PSMA-1007. Moreover, the potential of [^99mTc]Tc-iPSMA-BN as a theranostic pair with [¹⁷⁷Lu]Lu-iPSMA-BN was investigated. Methods: [^99mTc]Tc-iPSMA-BN was prepared under GMP conditions with radiochemical purities > 95%, showing specific recognition by PSMA and GRP receptors in prostate cancer cells and mice bearing PC tumors. Six healthy volunteers were enrolled, and [^99mTc]Tc-iPSMA-BN SPECT/CT imaging (740 MBq) was performed to estimate the dosimetry. The pilot clinical study included seven mCRPC and four mCSPC patients with prior androgen deprivation therapy. All patients had a recent [¹⁸F]-PSMA-PET/CT scan and were enrolled in this prospective study on their own signed behalf. Volumetric lesion target-to-background ratios (TBRs) were obtained from PET/CT and SPECT/CT images. Results: [^99mTc]Tc-iPSMA-BN effective radiation dose was 1.94 ± 0.39 mSv/740 MBq. A total of 178 lesions were detected via CT, 162 via [¹⁸F]-PSMA-1007 PET, and 155 via [^99mTc]Tc-iPSMA-BN SPECT. Three patients with mCRPC had higher TBR values on SPECT than on PET. [^99mTc]Tc-iPSMA-BN appears to have better lesion detection in patients with aggressive histologic transformation. Two-way ANOVA analysis revealed a significant difference in TBR values between patients with mCRPC and mCSPC (p < 0.05) but no difference between [¹⁸F]-PSMA-1007 and [^99mTc]Tc-iPSMA-BN (p > 0.05). In one patient, [¹⁷⁷Lu]Lu-iPSMA-BN showed a high correlation with [^99mTc]Tc-iPSMA-BN for lesions that concentrated radioactivity. Conclusions: [^99mTc]Tc-iPSMA-BN SPECT/CT is a promising alternative not only for diagnostic purposes but also for broadening the spectrum of PC patients who may benefit from radionuclide theranostics. The results justify the development of a clinical trial involving a significant number of patients with PC. Full article

Background: The early detection of transthyretin cardiac amyloidosis (ATTR-CM) is essential, with Tc-99m pyrophosphate scintigraphy (PYP scan) being a key diagnostic tool. Although a previously validated score has shown promise in predicting PYP scan positivity among patients with HFpEF, further evaluation in diverse cohorts is necessary. Objectives: To assess the effectiveness of the ATTR-CM score in predicting PYP scan positivity within our patient population. Methods: We analyzed patients referred for PYP with SPECT at the Cleveland Clinic from January 2012 to January 2020, all of whom had undergone echocardiography within the previous year. The ATTR-CM score was determined using the following criteria: Age (60–69, +2; 70–79, +3; ≥80, +4), sex (male, +2), hypertension (present, −1), left ventricular ejection fraction (LVEF <60%, +1), posterior wall thickness (≥12 mm, +1), and relative wall thickness (>0.57, +2). A score of ≥6 indicated high risk. Results: Among the 540 patients (32% female, 33% black), 27% had an LVEF <40%. The score demonstrated good discrimination by AUC, with consistent performance across different racial groups, sexes, and LVEF categories. For scores ≥6, sensitivity was lower in women and black patients; however, lowering the cutoff to 5 markedly improved sensitivity. Conclusions: The ATTR-CM score displayed consistently good performance by AUC across our cohort, including patients with HFrEF. Nevertheless, its sensitivity was reduced in black patients and women. Efforts to scale ATTR-CM diagnosis tools should be mindful of demographic differences in risk prediction models. Full article

Background/Objectives: Recurrence prediction for patients with PC and tumor sizes ranging between 1 and 4 cm, classified as T1b and T2, remains a controversial problem. We evaluated which risk factors, identified during the primary tumor surgery, might play a prognostic role in predicting disease progression. Methods: We retrospectively enrolled 363 patients with classic PC who were in follow-up (207 T1b, 156 T2), with tissue risk factors at surgery in 209/363 cases. In all cases, an ¹³¹I-whole-body scan, SPECT/CT, and US were employed to detect any metastases during follow-up, and histology was used to confirm lesions. In the absence of surgery, metastases were validated by radioisotopic and radiologic procedures, eventually culminating in a needle biopsy and sequential thyroglobulin changes. Results: Metastases occurred in 61/363 (16.8%) patients (24 T1b, 37 T2). In 50/61 cases, the following risk factors were identified: minimal extrathyroid tumor extension (mETE) alone in 12/50 patients, neck lymph node (LN) metastases in 8/50 cases, and multifocality/multicentricity (M/M) in 6/50 cases. In the remaining 24/50 cases, the risk factors were associated with each other. From a Cox regression multivariate analysis, metastasis development was significantly (p < 0.001) influenced by only mETE and LN metastases, with a shorter disease-free survival (log-rank test). Conclusions: The current study proves that mETE and neck LN metastases are associated with aggressive PC. While LN metastasis’ role is known, mETE’s role is still being debated, and was removed by the AJCC’s eighth edition because it was considered to not be associated with an unfavorable prognosis. However, this interpretation is not supported by the present study and, according to comparable studies, we suggest a revision of the mETE classification be considered in the next AJCC edition. Full article