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Objective Methods Results Interpretation Biallelic titin truncating variants (TTNtv) have been associated with a wide phenotypic spectrum, ranging from complex prenatal muscle diseases with dysmorphic features to adult‐onset limb‐girdle muscular dystrophy, with or without cardiac involvement. Given the size and complexity of TTN, reaching an unequivocal molecular diagnosis and precise disease prognosis remains challenging.In this case series, 12 unpublished cases and one already published case with biallelic TTNtv were collected from multiple international medical centers between November 2022 and September 2023. TTN mutations were detected through exome or genome sequencing. Information about familial and personal clinical history was collected in a standardized form. RNA‐sequencing and analysis of TTN exon usage were performed on an internal sample cohort including postnatal skeletal muscles, fetal skeletal muscles, postnatal heart muscles, and fetal heart muscles. In addition, publicly available RNA‐sequencing data was retrieved from ENCODE.We generated new RNA‐seq data on TTN exons and identified genotype–phenotype correlations with prognostic implications for each titinopathy patient (whether worsening or improving in prenatal and postnatal life) using percentage spliced in (PSI) data for the involved exons. Interestingly, thanks to exon usage, we were also able to rule out a titinopathy diagnosis in one prenatal case.This study demonstrates that exon usage provides valuable insights for a more exhaustive clinical interpretation of TTNtv; additionally, it may serve as a model for implementing personalized medicine in many other genetic diseases, since most genes undergo alternative splicing. [ABSTRACT FROM AUTHOR]

Background: 123I-meta-iodobenzylguanidine (mIBG) has been applied to patients with chronic heart failure (CHF). However, the relationship between 123I-mIBG activity and lethal arrhythmic events (ArE) is not well defined. This study aimed to determine this relationship in Japanese and European cohorts. Results: We calculated heart-to-mediastinum (H/M) count ratios and washout rates (WRs) of 827 patients using planar 123I-mIBG imaging. We defined ArEs as sudden cardiac death, arrhythmic death, and potentially lethal events such as sustained ventricular tachycardia, cardiac arrest with resuscitation, and appropriate implantable cardioverter defibrillator (ICD) discharge, either from a single ICD or as part of a cardiac resynchronization therapy device (CRTD). We analyzed the incidence of ArE with respect to H/M ratios, WRs and New York Heart Association (NYHA) functional classes among Japanese (J; n = 581) and European (E; n = 246) cohorts. We also simulated ArE rates versus H/M ratios under specific conditions using a machine-learning model incorporating 13 clinical variables. Consecutive patients with CHF were selected in group J, whereas group E comprised candidates for cardiac electronic devices. Groups J and E mostly comprised patients with NYHA functional classes I/II (95%) and II/III (91%), respectively, and 21% and 72% were respectively implanted with ICD/CRTD devices. The ArE rate increased with lower H/M ratios in group J, but the relationship was bell-shaped, with a high ArE rate within the intermediate H/M range, in group E. This bell-shaped curve was also evident in patients with NYHA classes II/III in the combined J and E groups, particularly in those with a high (> 15%) mIBG WR and with ischemic, but not in those with non-ischemic etiologies. Machine learning-based prediction of ArE risk aligned with these findings, indicating a bell-shaped curve in NYHA class II/III but not in class I. Conclusions: The relationship between cardiac 123I-mIBG activity and lethal arrhythmic events is influenced by the background of patients. The bell-shaped relationship in NYHA classes II/III, high WR, and ischemic etiology likely aids in identifying patients at high risk for ArEs. [ABSTRACT FROM AUTHOR]

Introduction: The term theragnostic refers to the combination of a predictive imaging biomarker with a therapeutic agent. The promising application of prostate-specific membrane antigen (PSMA)-based radiopharmaceuticals in the imaging and treatment of prostate cancer (PCa) patients opens the way to investigate a possible role of PSMA-based radiopharmaceuticals in cancers beyond the prostate. Therefore, the aim of this review was to evaluate the role of 177Lu-PSMA radioligand therapy (RLT) in malignancies other than prostate cancer by evaluating preclinical, clinical studies, and ongoing clinical trials. Methods: An extensive literature search was performed in three different databases using different combinations of the following terms: "Lu-PSMA", "177Lu-PSMA", "preclinical", "mouse", "salivary gland cancer", "breast cancer", "glioblastoma", "solid tumour", "renal cell carcinoma", "HCC", "thyroid", "salivary", "radioligand therapy", and "lutetium-177". The search had no beginning date limit and was updated to April 2024. Only articles written in English were included in this review. Results: A total of four preclinical studies were selected (breast cancer model n = 3/4). PSMA-RLT significantly reduced cell viability and had anti-angiogenic effects, especially under hypoxic conditions, which increase PSMA binding and uptake. Considering the clinical studies (n = 8), the complexity of evaluating PSMA-RLT in cancers other than prostate cancer was clearly revealed, since in most of the presented cases a sufficient tumour radiation dose was not achieved. However, encouraging results can be found in some types of diseases, such as thyroid cancer. Some clinical trials are still ongoing, and results from prospective larger cohorts of patients are awaited. Conclusions: The need for larger patient cohorts and more RLT cycles administered underscores the need for further comprehensive studies. Given the very preliminary results of both preclinical and clinical studies, ongoing clinical trials in the near future may provide stronger evidence of both the safety and therapeutic efficacy of PSMA-RLT in malignancies other than prostate cancer. [ABSTRACT FROM AUTHOR]

Dating to the Early Formative period, Vaquerias pottery is the earliest polychrome ceramic in the Argentine Northwest. Questions about its provenance, use and circulation persist, however. To address these, the authors employ, for the first time, an integrated methodology comprising petrographie, morphological, iconographie and contextual analyses of ceramic samples from three regions of north-western Argentina. The results suggest five distinct modes of manufacture of Vaquerias ceramics, the noncentralisation of their production, their wide geographic distribution and their use in a variety of functional contexts. The methodology is applicable elsewhere and illustrates the potential of this approach over traditional stylistic-morphological studies. Keywords: South America, Formative period, Vaquerias, petrography, polychrome ceramics, Introduction Vaquerias pottery is the oldest polychrome ceramic style in the Argentine Northwest and was manufactured by agro-pastoral village societies during the Early Formative period (seventh century BC to fifth [...]

Despite significant advances in glioma diagnosis and treatment, overall outcomes remain suboptimal. Exploring novel therapeutic avenues show promise in advancing the field. Theranostics, an evolving discipline integrating diagnosis and therapy, emerges as a particularly auspicious approach. However, an unmet need exists for glioma-associated biomarkers as theranostic targets. Immuno-positron emission tomography (Immuno-PET), a pioneering method uniting PET diagnostic precision with antibody specificity, holds potential for identifying cancer-associated biomarkers. This review aims to provide an updated overview of immuno-PET applications in gliomas. Notably, [44Sc]-CHX-A″-DTPA-Cetuximab-Fab targeting Epidermal Growth Factor Receptor (EGFR) has displayed promise in glioma xenografts, enabling potential imaging at 4 h post-injection. Similarly, [89Zr]-bevacizumab targeting vascular endothelial growth factor (VEGF) yielded encouraging results in preclinical models and a pioneering clinical trial for pediatric patients with diffuse intrinsic pontine glioma (DIPG). Several cell differentiation markers, including CD146, indicative of tumor aggressiveness, and CD11b, reflecting tumor-associated myeloid cells (TAMCs), proved effective targets for immuno-PET. Additionally, immuno-PET directed at prostate-specific antigen (PSMA) demonstrated efficacy in imaging glioma-associated neovasculature. While holding promise for precise diagnosis and treatment guidance, challenges persist in achieving target specificity and selecting suitable radionuclides. Further studies are imperative to advance the field and bridge a translational gap from bench to bedside. [ABSTRACT FROM AUTHOR]

Technetium-99m (99mTc)-diphosphonates represent the most common radiopharmaceutical used for bone scintigraphy. Even if the uptake in bone tissue has been widely explored, atypical uptake could be seen in soft tissue malignancies during bone scintigraphy. Increased vascularization and endothelium permeability represent front-row players in the biodistribution of the tracer, albeit other causes have been identified such as trauma, necrosis, the presence of calcification in metastasis, the pH of the tissue and consequently the type of ion concentration. The aim of this paper is to summarize the state of art of atypical soft tissue uptake seen in cancer tissues. The research was conducted on PubMed. The analysis of the literature suggests that calcium metabolism and ionic saturation have a pivotal role in the biodistribution of bone tracers. This phenomenon ranks in a complex scenario that includes carcinogenesis and cancer environment aspects. We also report two cases in our Institution in which atypical uptake in cancer tissues was observed. [ABSTRACT FROM AUTHOR]

This review provides an update of 18 F-fluorodeoxyglucose ([18F] FDG) for Brown adipose tissue (BAT) activity quantification, whose role is not completely understood. We conducted an unstructured search of the literature for any studies employing the [18F] FDG PET in BAT assessment. We explored BAT quantification both in healthy individuals and in different pathologies, after cold exposure and as a metabolic biomarker. The assessment of possible BAT modulators by using [18F] FDG PET is shown. Further PET tracers and novel developments for BAT assessments are also described. Further PET tracers and imaging modalities are under investigation, but the [18F] FDG PET is currently the method of choice for the evaluation of BAT and further multicentric trials are needed for a better understanding of the BAT physiopathology, also after cold stimuli. The modulation of BAT activity, assessed by [18F] FDG PET imaging, seems a promising tool for the management of conditions such as obesity and type 2 diabetes. Moreover, an interesting possible correlation of BAT activation with prognostic [18F] FDG PET indices in cancer patients should be assessed with further multicentric trials. [ABSTRACT FROM AUTHOR]

This is an observational multicentric cross-sectional study aiming at assessing the association between ABO blood groups and SARS-CoV-2 seroprevalence among the blood donors in Puglia region. Data on ABO and Rh blood groups and demographic characteristics were obtained from Blood Bank Information System. All donors were screened for SARS-CoV-2 IgG antibodies. Comparison of seroprevalence among blood groups and the association between the recorded variables and seroprevalence were evaluated. A total of 35,709 donors from 22 centers were included, with a seroprevalence of 6.8%. The distribution of ABO phenotypes was blood type O (46.8%), A (34.0%), B (14.7%), and AB (4.5%). Among the 2416 donors reactive for SARS-CoV-2 IgG, the prevalent phenotype was blood type O (43.1%), followed by A (37.7%), B (14.2%), and AB (5%). The seroprevalence of phenotype A and AB was 7.5%, followed by B (6.5%) and O (6.2%). According to the adjusted analysis, there was an increase in seroprevalence in groups A and AB, compared to group O, and an increase in males compared to females. A possible effect modification was observed after stratifying for sex (p = 0.0515). A significantly lower prevalence of blood type O was found compared to A and AB, whereas no association was observed between Rh factor and seroprevalence. We hypothesized that the A antigen present in blood type A and AB can play a role in the binding of SARS-CoV-2 to ACE2 receptors, resulting in an increased risk of infection. Furthermore, natural anti-A/anti-B antibodies produced in group O could block viral adhesion to cells and explain a lower risk of infection. [ABSTRACT FROM AUTHOR]

123I-mIBG-scintigraphy could be a useful stratifying tool for patients with heart failure (HF). The purpose of this retrospective study is to evaluate whether there are differences between men and women with HF in terms of the prediction of cardiac arrhythmic events (AE). A total of 306 patients, before implantable-cardioverter-defibrillator (ICD) implantation, were evaluated. They underwent 123I-mIBG-scintigraphy and an evaluation of the results was performed after 85 months of follow-up. Early and late planar and SPECT cardiac images were acquired. Heart-to-mediastinum ratio (HM) for planar images and the sum of the segmental scores (SS) for SPECT were calculated. In the general population, age, early SS (ESS), late SS (LSS), and ejection fraction (EF) were statistically significant for the prediction of AE at Cox regression, while early and late HM (eHM,lHM) were not significative for the prediction of AE. Population was divided into females and males and univariate analysis was conducted separately for the two cohorts: no significant variables for prediction of AE were found in females. For males, ESS, LSS, EF, and late HM were statistically significant predictors of AE. The overall survival was similar in males and females, but the risk of AE is lower in males than in females. 123I-mIBG represents a more effective tool for the prediction of AE in male patients than in women. [ABSTRACT FROM AUTHOR]

Background Titin truncating variants (TTNtvs) have been associated with several forms of myopathies and/ or cardiomyopathies. In homozygosity or in compound heterozygosity, they cause a wide spectrum of recessive phenotypes with a congenital or childhood onset. Most recessive phenotypes showing a congenital or childhood onset have been described in subjects carrying biallelic TTNtv in specific exons. Often karyotype or chromosomal microarray analyses are the only tests performed when prenatal anomalies are identified. Thereby, many cases caused by TTN defects might be missed in the diagnostic evaluations. In this study, we aimed to dissect the most severe end of the titinopathies spectrum. Methods We performed a retrospective study analysing an international cohort of 93 published and 10 unpublished cases carrying biallelic TTNtv. Results We identified recurrent clinical features showing a significant correlation with the genotype, including fetal akinesia (up to 62%), arthrogryposis (up to 85%), facial dysmorphisms (up to 73%), joint (up to 17%), bone (up to 22%) and heart anomalies (up to 27%) resembling complex, syndromic phenotypes. Conclusion We suggest TTN to be carefully evaluated in any diagnostic process involving patients with these prenatal signs. This step will be essential to improve diagnostic performance, expand our knowledge and optimise prenatal genetic counselling. [ABSTRACT FROM AUTHOR]