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The immunohistochemical determination of the Ki67 expression is regarded as a reliable method to monitor non small cell lung cancer (NSCLC) proliferation. However, cancer tissues are not uniform and the use of a small tumor sample in biopsy may not be accurate. Although positron emission tomography (PET) represents an alternative to biopsy, by providing the 3D functional and morphological distribution of cancer cells across the entire tumor volume, standardized uptake values (SUVs) exhibit poor accuracy. The purpose of this study is to identify quantitative features in 2-18FFDG PET images uniquely correlated with proliferating lung cancer cells that may perform better than SUVs in the evaluation of lung cancer proliferation. By using a xenograft NSCLC model implanted in 19 mice, we found that 89 textural parameters extracted from 3D 2-18FFDG uptake can be described by 6 independent principal components accounting for 95% of the total variance. One of these components features a significant and univocal correlation with 3D-stacked Ki67 staining immunohistochemical images (|r|>0.6;P

Prostate cancer (PCa) represents the most common tumor in male and one of the most relevant causes of death in Western countries. Androgen deprivation therapy (ADT) constitutes a widely used approach in advanced PCa. When PCa progresses in spite of ADT and castrate levels of testosterone, the severe clinical condition termed as metastatic castration-resistant prostate cancer (mCRPC) takes place. The only approach to mCRPC has been represented by chemotherapy with taxanes for many years. Nevertheless, recently introduced treatments such as 2nd generation antiandrogens (i.e. enzalutamide and abiraterone), cell immunotherapy with sipuleucel-T or targeted alpha therapy with 223Ra-dichloride, have dramatically changed mCRPC prognosis. These novel therapies call for an unmet need for imaging biomarkers suitable for patients’ pre-treatment stratification and response assessment. In this scenario, nuclear medicine can provide several metabolic and molecular probes for investigating pathological processes at a cellular and sub-cellular level. The aim of this paper is to review the most relevant findings of the literature published to date on this topic, giving particular emphasis to the pros and cons of each tracer and also covering future prospects for defining personalized therapeutic approaches.

Pulmonary vein (PV) isolation using cryoballoon (CB) catheter is generally characterized by a high radiation and contrast media exposure. A new dielectric imaging system (KODEX–EPD imaging system) allows pulmonary vein (PV) occlusion assessment without dye use. The purpose of this study was to verify the feasibility of reducing the radiation and dye use during CB ablation in patients with atrial fibrillation (AF) using the new dielectric imaging system. In a retrospective, single center study, we enrolled 34 consecutive patients with paroxysmal AF divided in two groups: 17 patients in Conventional Group underwent the procedure under fluoroscopy guidance before the new system introduction, while 17 patient in KODEX–EPD Group underwent the procedure under fluoroscopy and KODEX–EPD imaging system guidance. There were no differences in any clinical and anatomical characteristics between the two study groups. Overall procedure time was comparable between the two groups (69 [IQR 63–98] min in Conventional Group vs. 65 [IQR 58–74] min in KODEX–EPD Group, p = 0.16), while fluoroscopy time (8 [IQR 5–9] min vs. 11 [IQR 9–12] min, p = 0.014) and dye use (35 [IQR 28–45] ml vs. 70 [IQR 57–83] ml, p

Background: Heart rate (HR), mean arterial pressure (MAP) and carotid intima–media thickness (cIMT) are moderately heritable cardiovascular traits, but the environmental effects on the longitudinal change of their heritability have never been investigated. Methods: 368 Italian and Hungarian twins (107 monozygotic, 77 dizygotic) underwent oscillometric measurement and B-mode sonography of bilateral carotid arteries in 2009/2010 and 2014. Within- -individual/cross-study wave, cross-twin/within-study wave and cross-twin/cross-study wave correlations were estimated, and bivariate Cholesky models were fitted to decompose the total variance at each wave and covariance between study waves into additive genetic, shared and unique environmental components. Results: For each trait, a moderate longitudinal stability was observed, with within-individual/crosswave correlations of 0.42 (95% CI: 0.33–0.51) for HR, 0.34 (95% CI: 0.24–0.43) for MAP, and 0.23 (95% CI: 0.12–0.33) for cIMT. Cross-twin/cross-wave correlations in monozygotic pairs were all significant and substantially higher than the corresponding dizygotic correlations. Genetic continuity was the main source of longitudinal stability, with across-time genetic correlations of 0.52 (95% CI: 0.29–0.71) for HR, 0.56 (95% CI: 0.31–0.81) for MAP, and 0.36 (95% CI: 0.07–0.64) for cIMT. Overlapping genetic factors explained respectively 57%, 77%, and 68% of the longitudinal covariance of the HR, MAP and cIMT traits. Conclusions: Genetic factors have a substantial role in the longitudinal change of HR, MAP and cIMT; however, the influence of unique environmental factors remains relevant. Further studies should better elucidate whether epigenetic mechanisms have a role in influencing the stability of the investigated traits over time.

Purpose To assess the presence and pattern of incidental interstitial lung alterations suspicious of COVID-19 on fluorine-18-fluorodeoxyglucose positron emission tomography (PET)/computed tomography (CT) ([18F]FDG PET/CT) in asymptomatic oncological patients during the period of active COVID-19 in a country with high prevalence of the virus. Methods This is a multi-center retrospective observational study involving 59 Italian centers. We retrospectively reviewed the prevalence of interstitial pneumonia detected during the COVID period (between March 16 and 27, 2020) and compared to a pre-COVID period (January–February 2020) and a control time (in 2019). The diagnosis of interstitial pneumonia was done considering lung alterations of CT of PET. Results Overall, [18F]FDG PET/CT was performed on 4008 patients in the COVID period, 19,267 in the pre-COVID period, and 5513 in the control period. The rate of interstitial pneumonia suspicious for COVID-19 was significantly higher during the COVID period (7.1%) compared with that found in the pre-COVID (5.35%) and control periods (5.15%) (p Conclusions A significant increase of interstitial pneumonia incidentally detected with [18F]FDG PET/CT has been demonstrated during the COVID-19 pandemic. A majority of interstitial pneumonia were FDG-avid. Our results underlined the importance of paying attention to incidental CT findings of pneumonia detected at PET/CT, and these reports might help to recognize early COVID-19 cases guiding the subsequent management.

Purpose: The present study was conducted to compare the pattern of brain [18F] FDG uptake in suspected non-Alzheimer’s pathophysiology (SNAP), AD, and healthy controls using 2-deoxy-2-[18F]fluoroglucose ([18F] FDG) positron emission tomography imaging. Cerebrospinal fluid (CSF) biomarkers amyloid-β1-42 peptide (Aβ1-42) and tau were used in order to differentiate AD from SNAP. Methods: The study included 43 newly diagnosed AD patients (female = 23; male = 20) according to the NINCDS-ADRDA criteria, 15 SNAP patients (female = 12; male =3), and a group of 34 healthy subjects that served as the control group (CG), who were found to be normal at neurological evaluation (male = 20; female = 14). A battery of neuropsychological tests was administrated in AD and SNAP subjects; cerebrospinal fluid assay was conducted in both AD and SNAP as well. Brain PET/CT acquisition was started 30 ± 5min after [18F] FDG injection in all subjects. SPM12 [statistical parametric mapping] implemented in MATLAB 2018a was used for the analysis of PET scans in this study. Results: As compared to SNAP, AD subjects showed significant hypometabolism in a wide cortical area involving the right frontal, parietal, and temporal lobes. As compared to CG, AD subjects showed a significant reduction in [18F] FDG uptake in the parietal, limbic, and frontal cortex, while a more limited reduction in [18F] FDG uptake in the same areas was found when comparing SNAP to CG. Conclusions: SNAP subjects show milder impairment of brain [18F] FDG uptake as compared to AD. The partial overlap of the metabolic pattern between SNAP and AD limits the use of [18F] FDG PET/CT in effectively discriminating these clinical entities.

IntroductionSARS-CoV-2 is a respiratory virus supposed to enter the organism through aerosol or fomite transmission to the nose, eyes and oropharynx. It is responsible for various clinical symptoms, including hyposmia and other neurological ones. Current literature suggests the olfactory mucosa as a port of entry to the CNS, but how the virus reaches the olfactory groove is still unknown. Because the first neurological symptoms of invasion (hyposmia) do not correspond to first signs of infection, the hypothesis of direct contact through airborne droplets during primary infection and therefore during inspiration is not plausible. The aim of this study is to evaluate if a secondary spread to the olfactory groove in a retrograde manner during expiration could be more probable.MethodsFour three-dimensional virtual models were obtained from actual CT scans and used to simulate expiratory droplets. The volume mesh consists of 25 million of cells, the simulated condition is a steady expiration, driving a flow rate of 270 ml/s, for a duration of 0.6 seconds. The droplet diameter is of 5 μm.ResultsThe analysis of the simulations shows the virus to have a high probability to be deployed in the rhinopharynx, on the tail of medium and upper turbinates. The possibility for droplets to access the olfactory mucosa during the expiratory phase is lower than other nasal areas, but consistent.DiscussionThe data obtained from these simulations demonstrates the virus can be deployed in the olfactory groove during expiration. Even if the total amount in a single act is scarce, it must be considered it is repeated tens of thousands of times a day, and the source of contamination continuously acts on a timescale of several days. The present results also imply CNS penetration of SARS-CoV-2 through olfactory mucosa might be considered a complication and, consequently, prevention strategies should be considered in diseased patients.

Resumen Introduccion Nuestro objetivo fue evaluar los cambios metabolicos corticales y el resultado clinico en los pacientes afectados por la hidrocefalia idiopatica de presion normal (iNPH) despues de la colocacion de una derivacion ventriculoperitoneal (VP). Materiales y metodos Diez pacientes afectados por la sospecha de iNPH se sometieron a una evaluacion de la hidrodinamica del LCR basada en una prueba de infusion lumbar. El principal criterio de seleccion para la cirugia se baso en la elasticidad intracraneal (EI) > 0,30. Todos los sujetos con una EI > 0,30 se sometieron a una exploracion PET con 18 fluorodesoxiglucosa (18F-FDG) en la linea de base (PET1) y un mes despues de la cirugia (PET2). Ademas, los mismos pacientes fueron sometidos a una evaluacion clinica antes y un mes despues de la cirugia mediante pruebas neuropsicologicas y analisis de la marcha. Resultados Se realizo un numero total de 20 exploraciones de PET 18F-FDG en todos los pacientes reclutados. En comparacion con la PET1, la PET2 mostro un aumento en el consumo de glucosa en el lobulo frontal izquierdo y el lobulo parietal izquierdo en la PET2 en comparacion con la PET1 (p Conclusiones La mejora en 18F-FDG PET del metabolismo de la glucosa podria considerarse un marcador de imagen util para la evaluacion de la respuesta de la iNPH a la derivacion ventriculoperitoneal.

OBJECTIVE Celocentesis is an invasive technique that can provide prenatal diagnosis of single-gene disorders, from as early as 7 weeks' gestation. The objective of this study was to examine the safety of celocentesis. METHODS In this prospective study, celocentesis was performed for prenatal diagnosis of hemoglobinopathy in 402 singleton pregnancies in which both parents were carriers of β-thalassemia or sickle cell disease trait. We assessed procedure-related maternal discomfort or pain, success of sampling and obtaining results, pregnancy outcome and postnatal follow-up. RESULTS First, celocentesis was carried out at a median gestational age of 8.6 (range, 6.9-9.9) weeks and celomic fluid was successfully aspirated in 99.8% of cases. Second, 67% of women had no or only mild discomfort, 18% had moderate discomfort, 12% had mild-to-moderate pain and 3% had severe pain. Third, prenatal diagnosis from analysis of the celomic fluid was successful in 93.8% cases, and in the last 121 cases, it was always successful. Fourth, in all cases of successful sampling and analysis of celomic fluid, the diagnosis was concordant with results obtained from additional prenatal or postnatal testing. Fifth, in addition to diagnosis of hemoglobinopathy, quantitative fluorescence polymerase chain reaction analysis, which was performed to evaluate maternal contamination using several markers for chromosomes X, Y, 21, 18 and 13, led to the accurate diagnosis of chromosomal aneuploidy. Sixth, in all cases of an affected fetus diagnosed by celocentesis in which the parents chose termination of pregnancy, this was carried out

Liver is the predominant site of metastatization for neuroendocrine tumors (NETs). Up to 75% of patients affected by intestinal NETs present liver metastases at diagnosis. For hepatic NET, surgery represents the most effective approach but is often unfeasible due to the massive involvement of multifocal disease. In such cases, chemotherapy, peptide receptor radionuclide therapy and loco-regional treatments may represent alternative therapeutic options. In particular, radioembolization with 90Y-microspheres has been introduced as a novel technique for treating hepatic malignant lesions, combining the principles of embolization and radiation therapy. In order to evaluate the response to 90Y-radioembolization, standard radiologic criteria have been demonstrated to present several limitations. 18Fluoro-deoxyglucose (FDG) Positron Emission Tomography (PET) is routinely used for monitoring the response to therapy in oncology. Nevertheless, NETs often present low glycolytic activity thus the conventional 18FDG PET may not be adequate for these tumors. For many years, somatostatin receptor scintigraphy (SRS) with 111In-pentetreotide has been used for diagnosis and staging of NETs. More recently, three 68Ga-DOTA-compounds have been developed and introduced for the imaging of NETs with PET technology. The aim of the present paper was to review the existing literature concerning the application of different metabolic and molecular probes for the imaging evaluation of hepatic NETs following 90Y-RE.

BACKGROUND The effectiveness of colonoscopy strictly depends on adequate bowel cleansing. Recently, a 1 L polyethylene glycol plus ascorbate (PEG-ASC) solution (Plenvu; Norgine, Harefield, United Kingdom) has been introduced on the evidence of three phase-3 randomized controlled trials, but it had never been tested in the real-life. AIM To assess the effectiveness and tolerability of the 1 L preparation compared to 4 L and 2 L- PEG solutions in a real-life setting. METHODS All patients undergoing a screening or diagnostic colonoscopy after a 4, 2 or 1 L PEG preparation, were consecutively enrolled in 5 Italian centers from September 2018 to February 2019. The primary endpoints of the study were the assessment of bowel cleansing success and high-quality cleansing of the right colon. The secondary endpoints were the evaluation of tolerability, adherence and safety of the different bowel preparations. Bowel cleansing was assessed through the Boston Bowel Preparation Scale. Adherence was defined as consumption of at least 75% of each dose, while tolerability was evaluated through a semi-quantitative scale. Safety was systematically monitored through adverse events reporting. RESULTS Overall, 1289 met the inclusion criteria and were enrolled in the study. Of these, 490 patients performed a 4 L-PEG preparation (Selgesse®), 566 a 2 L-PEG cleansing (Moviprep® or Clensia®) and 233 a 1 L-PEG preparation (Plenvu®). Bowel cleansing by Boston Bowel Preparation Scale was 6.5 ± 1.5 overall and 6.3 ± 1.5, 6.2 ± 1.5, 7.3 ± 1.5 (P < 0.001) in the subgroups of 4 L, 2 L and 1 L-PEG preparation, respectively. Cleansing success was achieved in 72.4%, 74.1% and 90.1% (P < 0.001), while a high-quality cleansing of the right colon in 15.9%, 12.0% and 41.4% (P < 0.001) for 4 L, 2 L and 1 L-PEG preparation groups, respectively. The 1 L preparation was the most tolerated compared to the 2 and 4 L-PEG solutions in the absence of serious adverse events within any of the three groups. Multiple regression models confirmed 1 L PEG-ASC preparation as an independent predictor of overall cleansing success, high-quality cleansing of the right colon and of tolerability. CONCLUSION This study supports the effectiveness and tolerability of 1 L PEG-ASC, also showing it is an independent predictor of overall cleansing success, high-quality cleansing of the right colon and of tolerability.

Here we proposed the most recent innovations in the use of Breast Specific Gamma Imaging with 99mTc-sestamibi for the management of breast cancer patients. To this end, we reported the recent discoveries concerning: a) the implementation of both instrumental devices and software, b) the biological mechanisms involved in the 99mTc-sestamibi uptake in breast cancer cells, c) the evaluation of Breast Specific Gamma Imaging with 99mTc-sestamibi as predictive markers of metastatic diseases. In this last case, we also reported preliminary data about the capability of Breast Specific Gamma Imaging with 99mTc-sestamibi to identify breast cancer lesions with high propensity to form bone metastatic lesions due to the presence of Breast Osteoblast-Like Cells.

The association of situs inversus totalis and left ventricular noncompaction is very rare and poses several and unique challenges if endo-epicardial ablation has to be performed, both for anatomical access to the target area and for arrhythmia complexity. We report a case of incessant ventricular tachycardia with endo-epicardial involvement that required ablation in both surfaces to obtain final noninducibility.

Human papilloma virus infection (HPV) is the most common sexually transmitted disease. Little is known about male infection. Nonavalent vaccine against types 6/11/16/18/31/33/45/52/58 was approved and neutral gender immunization programs have been proposed. This study evaluates the potential impact of nonavalent vaccine compared to quadrivalent in male living in Sicily (Italy). 58.7% of samples were HPV positive and forty-four types of HPV were identified. A significant higher estimated coverage of nonavalent vaccine than quadrivalent was observed (64.3% vs. 45.8%), with absolute and relative additional impact of 20.1% and 47.2%, respectively. Low impact of the vaccine were calculated as the empirical probability of HPV genotypes 6/11/16/18/31/33/45/52/58 alone or in combination; the high impact as empirical probability of HPV6/11/16/18/31/33/45/52/58 genotypes alone or in association with other genotypes. The potential impact of the nonavalent vaccine vs quadrivalent was significant for low and high impact (29.7% > 18:8%; 34:6% > 26.6%, respectively). Particularly, in men with lesions and risky sexual contact was significant only for low impact (35.5% > 29.7%; 31.4% > 19.7%, respectively). In partners with positive females was significant for low impact (26.3% > 15.1%) and high impact (33.7% > 23.2%). Nonavalent vaccine offers broader protection in men with HPV positive partners, who would have a potential role in the transmission of the infection.

Background: It is unclear how multiple sclerosis (MS) affects the severity of Covid-19. Methods: Hospitalization, Intensive Care Unit (ICU) admission and death after Covid-19 diagnosis of 1362 MS patients were compared to the age and sex-matched Italian population in a retrospective observational case-cohort study with population-based control. The observed vs the expected events were compared in the whole MS cohort and in different subgroups (higher-risk: EDSS>3 or at least one comorbidity, lower-risk: EDSS

Purpose The primary aim of this multicenter retrospective analysis is to examine the role of(18)F-choline PET/CT as a diagnostic tool for staging and restaging prostate cancer (PCa) in a large population in the light of 10 years of clinical experience. A secondary aim of the study is to produce data on the predictors of a positive(18)F-choline PET/CT result in the setting of PCa primaries and biochemical recurrences. Materials and Methods This multicenter retrospective cohort study is based on data collected by 9 Italian nuclear medicine departments. Between October 2008 and September 2019, 3343 men underwent(18)F-choline PET/CT scans before receiving definitive treatments for a primary PCa or biochemical recurrence. Inclusion criteria were (1) histologically proven PCa (on surgical specimens or prostate biopsies from patients not treated surgically) and (2) availability of clinical and pathological data, including serum prostate specific antigen (PSA) level at the time of PET/CT scanning. Results F-18-choline PET/CT was performed in 545 cases (16.4%) for cancer staging and in 2798 (83.6%) for restaging purposes, and the result was positive in 540 (99.1%) for the former and 1993 (71.2%) for the latter. A positive PET/CT result was always associated with a high Gleason score (>7) and high PSA levels (P< 0.01). The percentage of patients with a PSA threshold less than 1.0 ng/mL for performing PET/CT was higher in the years 2014 to 2019 (n = 341, 25% of cases) than during the previous period (n = 148, 16%; in 2008-2013). When used for staging purposes, receiver operating characteristic analysis showed that PSA levels of 9.2, 16.4, and 16.6 ng/mL were the optimal cutoffs for distinguishing between positive and negative PET/CT findings for local disease, lymph node involvement, and metastasis, respectively. In the restaging setting, a PSA level of 1.27 ng/mL was the optimal cutoff for distinguishing between a positive and negative PET/CT scan. Conclusions F-18-choline PET/CT can help identify early recurrences, even in the case of low PSA levels (

Background“Conversion therapy” practices (CTP) refer to a heterogeneous set of treatments and activities that share the common goal of suppressing, “repairing,” or otherwise preventing expressions of transgender, lesbian, gay, bisexual, or queer identities. This study aimed to elicit details from those with direct experience and assess concordance between CTP experiences and the definition of CTP included in federal legislation aiming to deter CTP.MethodsWe conducted an anonymous online survey of adults (>18 years) in Canada between August 18 and December 2, 2020. Participants were recruited through social media, CTP survivor networks, and word-of-mouth.ResultsOf 51 respondents with direct experience of CTP, 16 were transgender, 34 were cisgender. Most respondents lived in Alberta, British Columbia, Ontario, or Quebec. 49% experienced CTP in a licensed healthcare provider office, 45% at a faith-based organization, and 36% at an unlicensed counselor office (categories not mutually exclusive). Age at first CTP experience ranged from 2 to 44 years of age (mean: 17.8 years; median: 17 years). Respondents experienced CTP for InterpretationResults from this Canadian survey of adults with experience of CTP indicate that legislative attempts to ban CTP must be expanded (e.g., to include adults and practices that do not concord with previously drafted definitions) and paired with other prevention efforts.

Introduction: Limited data are available on the course of Coronavirus disease 2019 (COVID-19) in people with Multiple Sclerosis (MS). More real-world data are needed to help the MS community to manage MS treatment properly. In particular, it is important to understand the impact of immunosuppressive therapies used to treat MS on the outcome of COVID-19.Methods: We retrospectively collected data on all confirmed cases of COVID-19 in MS patients treated with ocrelizumab, followed in two MS Centers based in University Hospitals in Northern Italy from February 2020 to June 2021.Results: We identified 15 MS patients treated with ocrelizumab with confirmed COVID-19 (mean age, 50.47 ± 9.1 years; median EDSS, 3.0; range 1.0–7.0). Of these, 14 were confirmed by nasal swab and 1 was confirmed by a serological test. COVID-19 severity was mild to moderate in the majority of patients (n = 11, 73.3%; mean age, 49.73; median EDSS 3.0). Four patients (26.7%; mean age, 52.5 years; median EDSS, 6) had severe disease and were hospitalized; one of them died (age 50, EDSS 6.0, no other comorbidities). None of them had underlying respiratory comorbidities.Conclusion: This case series highlights the large variability of the course of COVID-19 in ocrelizumab-treated MS patients. The challenges encountered by the healthcare system in the early phase of the COVID-19 pandemic might have contributed to the case fatality ratio observed in this series. Higher MS-related disability was associated with a more severe COVID-19 course.

Background Isthmus-dependent right atrial flutter is the most frequently encountered atrial flutter in clinical practice (80–90% of atrial flutters). Purpose The aim of our study was to assess as first experience the feasibility and safety of radiofrequency catheter ablation (RFCA) of cavo-tricuspid isthmus (CTI) guided by KODEX-EPD imaging system in patients presenting with typical atrial flutter (AFL). Methods 16 consecutive patients (mean age 68,46±7,8 years, 80% males) with diagnosis of AFL underwent RFCA guided by KODEX-EPD imaging system. In 15 patients the analysis performed during tachycardia showed a counter-clockwise activation. In 1 patient no tachycardia could be induced and the ablation was performed in sinus rhythm with fixed pacing from the coronary sinus. The KODEX-EPD imaging system was also used to guide ablation and to confirm persistent bidirectional block after ablation. Results Mean procedural time was 37,6±8,2 min, mean radiofrequency ablation time was 7,8±3,4 min, and mean fluoroscopy time was 2,1±1,2 min. All procedures were acutely successful with interruption of AFL during RFCA along the inferior CTI in 15 patients and achievement of the bidirectional conduction block in 16 patients proven by atrial pacing medial and lateral to the ablation line. There were no major procedural and 30-day complications. Over a mean follow-up of 18 months, we observed no recurrence of arrhythmia and no complications. Conclusions Our study shows that RFCA for AFL using the KODEX-EPD imaging system is feasible, safe, and effective. Funding Acknowledgement Type of funding sources: None.

Background: The aim of this study was to evaluate how the high sensitivity C-reactive protein (hs-CRP) values influence the risk of carotid plaque instability in association with other cardiovascular risk factors. Methods: One hundred and fifty-six carotid plaques from both symptomatic and asymptomatic patients requiring surgical carotid endarterectomy were retrospectively collected. According to the modified American Heart Association, atherosclerosis plaques have been histologically distinguished into unstable and stable. The following anamnestic and hematochemical data were also considered: age, gender, hypertension, diabetes mellitus, smoking habit, therapy, low-density lipoprotein (LDL)-C, kidney failure and hs-CRP. Results: The results of our study clearly show that high levels of hs-CRP significantly increase the carotid plaque instability in dyslipidemic patients. Specifically, a 67% increase of the risk of carotid plaque instability was observed in patients with high LDL-C. Therefore, the highest risk was observed in male dyslipidemic patients 2333 (95% CI 0.73–7.48) and in aged female patients 2713 (95% CI 0.14–53.27). Discussion: These data strongly suggest a biological relationship between the hs-CRP values and the alteration of lipidic metabolism mostly in male patients affected by carotid atherosclerosis. The measurement of hs-CRP might be useful as a potential screening tool in the prevention of atheroscletotic disease.

Background A new catheter-based 3D dielectric imaging modality to guide electrophysiology ablation procedures that does not require contact or X-ray to image and offers new benefits for cryoablation procedures. Case presentation A 51-year-old male with paroxysmal atrial fibrillation was admitted to our hospital for atrial fibrillation ablation that was performed using cryoballoon fourth generation combined with a novel wide-band dielectric imaging system [KODEX-EPD (EPD Solutions, a Philips company)]. Conclusions This system allowed to visualize left common pulmonary vein before balloon positioning and then confirmed by pulmonary vein angiography.

The aim of this study was to investigate the prognostic value of neutrophil-to-lymphocyte ratio (NLR) and its relationship with several metabolic parameters obtained through PET in intrahepatic cholangiocarcinoma (ICC) submitted to radioembolization with Y-microspheres (Y-radioembolization).Records of 20 subjects affected by ICC and submitted to Y-radioembolization were retrospectively evaluated. In all cases, pretreatment NLR was carried out and fluorine-18-fluorodeoxyglucose (F-FDG) PET/CT was acquired with the calculation of the following metabolic parameters: maximum and mean standardized uptake value (SUVmax and SUVmean), metabolic total volume and total lesion glycolysis. After Y-radioembolization, all patients underwent regular imaging and laboratory follow-up.All patients presented F-FDG-avid hepatic tumors at pretreatment PET/CT examination. NLR significantly correlated with SUVmax (r = 0.64; P = 0.002) and SUVmean (r = 0.67; P = 0.001). After treatment with Y-microspheres, the mean OS resulted 12.5 ± 1.5 months. When the average pretreatment NLR value (i.e. 2.7) was used as a cutoff for patients' stratification, subjects with low NLR (2.7) had a significantly longer OS than those with high NLR (2.7). At Cox regression analysis including bilirubin, age, the presence of extrahepatic disease, hepatitis C virus/hepatitis B virus status and PET-derived parameters, only NLR resulted to be a significant predictor of OS (P = 0.01; hazard ratio = 13.1, 95% confidence interval = 1.6-102.7).NLR is correlated with SUVmax-mean values in ICC and resulted to be an easy available predictor of survival in patients submitted to treatment with Y-microspheres.

Background:68Ga-PSMA is a widely useful PET/CT tracer for prostate cancer imaging. Being a transmembrane protein acting as a glutamate carboxypeptidase enzyme, PSMA is highly expressed in prostate cancer cells. PSMA can also be labeled with 64Cu, offering a longer half-life and different resolution imaging. Several studies documented bio-distribution and pitfalls of 68Ga-PSMA as well as of 64Cu- PSMA. No data are reported on differences between these two variants of PSMA. Our aim was to evaluate physiological distribution of these two tracers and to analyze false positive cases.Methods:We examined tracer bio-distribution in prostate cancer patients with negative 68Ga-PSMA PET/CT (n=20) and negative 64Ga-PSMA PET/CT (n=10). A diagnostic pitfall for each tracer was documented.Results:Bio-distribution of both tracers was similar, with some differences due to renal excretion of 68Ga- PSMA and biliary excretion of 64Cu-PSMA. 68Ga-PSMA uptake was observed in sarcoidosis while 64Cu- PSMA uptake was recorded in pneumonitis.Discussion:Both tracers may present similar bio-distribution in the human body, with similar uptake in exocrine glands and high intestinal uptake. Similarly to other tracers, false positive cases cannot be excluded in clinical practice.Conclusion:The knowledge of difference in bio-distribution between two tracers may help in interpretation of PET data. Diagnostic pitfalls can be documented, due to the possibility of PSMA uptake in inflammation. Our results are preliminary to future studies comparing diagnostic accuracies of 68Ga-PSMA and 64Cu-PSMA.

Background: The aim of this study was to evaluate the safety and efficacy of repeated administration of 90Y-microspheres in intrahepatic cholangiocarcinoma (ICC) relapsed after the first radioembolization (RE). Methods: Nine patients with ICC relapsed after the first 90Y-RE were enrolled. Six patients presented recurrence in the right hepatic lobe, 3 in the left lobe. All subjects underwent a second administration of 90Y-resin microspheres. Toxicity was assessed according to Common Terminology Criteria for Adverse Events (CTCAE, version 4.02). After the repeated treatment, all patients were submitted to follow-up with laboratory, imaging, and clinical examinations. Results: The mean cumulative activity administered considering both treatments was 2.7 ± 0.5 GBq. After the second treatment, 3 patients presented complete metabolic response (33.3%) and 6 had partial response (66.6%). The following adverse events were registered: transient increased levels of liver enzymes (grade 1 = 4; grade 2 = 2), hyperbilirubinemia (grade 1 = 2), ascites (grade 2 = 1), and duodenal ulcer (grade 2 = 1). Two patients developed a significant shrinking of the targeted hepatic lobe, as for radiation lobectomy. No case of RE-induced liver disease was registered. Median overall survival was 16.5 ± 1.4 months after the first RE. Conclusions: The authors' results suggest that repeated administration of 90Y-microspheres may be considered in patients affected by ICC relapsed after the first 90Y-RE.

BACKGROUND The purpose of this study was to compare the short-term outcomes of laparoscopic right hemicolectomy between intracorporeal (IA) and extracorporeal (EA) anastomosis techniques. METHODS A retrospective chart review of 77 consecutive patients who underwent laparoscopic right hemicolectomy from January 2016 to June 2018 was performed. The intracorporeal group included 36 patients and the extracorporeal group 41 patients. RESULTS Patient demographics and disease-related characteristics were similar. Mean operative time was 152±38.3 minutes in IA vs. 148±34.8 minutes in EA (p = 0.664). IA was not associated with less overall postoperative complications and decreased rate of surgical site infections. There was no statistically significant difference in the incidence of postoperative leak, length of stay, mortality in both groups. There was no perioperative difference in median number of lymph node harvested. There was statistically significant difference in the length of larger incision [50 (50-70) mm in IA vs 80 (70-100) mm in EA; p

Schistosomiasis is one of the most important parasitic diseases and it is endemic in tropical and subtropical areas. Clinical and laboratory data are fundamental for the diagnosis of schistosomiasis, but diagnostic imaging techniques such as x-rays, ultrasound (US), computed tomography (CT), magnetic resonance imaging (MRI), and positron emission tomography/computed tomography (PET/CT) may be helpful in the evaluation of disease severity and complications. In this context, the aim of this review is to explore the actual role of diagnostic imaging in the diagnosis of schistosomiasis, underlining advantages and drawbacks providing information about the utilization of diagnostic imaging techniques in this context. Furthermore, we aim to provide a useful guide regarding imaging features of schistosomiasis for radiology and nuclear medicine physicians of non-endemic countries: in fact, in the last years non-endemic countries have experienced important flows of migrants from endemic areas, therefore it is not uncommon to face cases of this disease in daily practice.

Diagnosis of pancreatic cancer is challenging in the initial phases because its progression is rapid. The pancreatic tail and body roughly accounts for 20-30% of all cancerous cases. The standard treatment for symptomatic benign, malignant, and premalignant diseases of the pancreatic tail and body is distal pancreatectomy. This technique has been modified over the years to fit certain indications, with the goal of enhancing post-operative results as well as reducing patient trauma. In cases of a premalignant and symptomatic benign condition, the spleen must be preserved either using Kimura's splenic vessel preservation technique or Warshaw's splenic vessel resection technique. A better long-term prognosis is ensured by regional lymph node dissection and radical R0 resection. Radical antegrade modular pancreatosplenectomy was proposed to tackle the shortcomings of traditional surgery for pancreatic tail and body cancer. In this review, study techniques and results of laparoscopic distal pancreatectomy for malignant and benign pancreatic ailments were described with the intention of providing knowledge on various suitable techniques reported for pancreatic cancer treatment. Furthermore, this study will serve as a ready reckoner for surgeons and could serve to boost their confidence levels during surgery by avoiding confusion on the selection of suitable for the pancreatic diseases diagnosed.

Funding Acknowledgements Type of funding sources: None. Background An early and comprehensive rhythm-control therapy emerges as a need to treat AF in an effective way and to improve the ablation outcomes, in terms of arrhythmia-free survival. Purpose We aimed to investigate the importance of timing of ablation in preventing AF recurrences. Methods 153 consecutive patients (pts) undergoing AF ablation from the CHARISMA registry at 8 Italian centres were included. Ablations were guided by a novel radiofrequency ablation catheter with local impedance (LI)-sensing capability through a dedicated algorithm (DirectSense, Boston Scientific). Pts were grouped as early treated (ET) if the procedure was performed within 1 year after the first AF episode and as delayed treated (DT) if admitted for ablation after more than 1 year. The ablation endpoint was PVI as assessed by entrance and exit block. Post-ablation follow-up was scheduled at 3, 6 and 12 months. AF and atrial tachycardia (AT) recurrences were considered as long-term endpoint. Results Of the 153 pts enrolled (69.9% male, 59 ± 10 years, 61.4% paroxysmal AF, 38.6% persistent AF), 123 (80.4%) met Class I indications, 23 (15%) Class IIa indications and 7 (4.6%) Class IIb indications according to current ESC AF guidelines. The mean time to ablation procedure from the first AF episode was 1034 ± 1483 days. Eighty pts (52.3%) were included in ET group, whereas 73 pts (47.7%) in DT group. No differences were found between AF type in terms of ablation strategy (53.3% of the cases -52 out 94- were classified as ET for paroxysmal AF vs 47.5% of the cases -28 out 59- were ET for persistent AF, p = 0.4346). At the end of the procedures, all PVs had been successfully isolated in all study pts. During a mean follow-up of 366 ± 130 days, 18 pts (11.8%) suffered an AF/AT recurrence after the 90-day blanking period. Recurrences occurred mostly in the DT group compared to the ET one (13 out 73 -17.8%- vs 5 out 80 -6.3%-, p = 0.042) and the time to AT/AF recurrence was longer in the ET group (HR = 0.2876, 95%CI: 0.1029 to 0.8038; p = 0.0181). On multivariate logistic analysis adjusted for baseline confounders, only hypertension (HR = 4.66, 95%CI: 1.5 to 14.48, p = 0.0081) was independently associated with recurrences. An early rhythm-control therapy was associated with a low risk of recurrences beyond the hypertension risk factor, ranging from 2% (no hypertension and an ET ablation therapy) to 30.3% (with hypertension and a DT procedure) (Figure 1). Conclusion A LI-guided ablation strategy for PVI proved to be safe and effective and resulted in a very high recurrence-free rate. An early rhythm-control therapy in the absence of common risk factors was associated with the lowest rate of recurrences. Abstract Figure. AT/AF Recurrence

Funding Acknowledgements Type of funding sources: None. Background It has been demonstrated that an ablation strategy based on local impedance (LI) algorithm is helpful in guiding successful ablation of atrial fibrillation (AF) cases. How the magnitude and the course of LI drop could impact the effectiveness of ablation has to be proved. Purpose We aimed to evaluate LI drop characteristics in predicting effective radiofrequency (RF) ablation of consecutive AF cases. Methods Consecutive patients undergoing AF ablation at 8 Italian centers were included in the CHARISMA registry. A RF ablation catheter equipped with mini-electrodes technology and a dedicated algorithm was used to measure LI and to guide ablation. For our purpose, we defined the time to drop (τ) as the time for the first deflection of LI drop to the plateau. RF applications were targeted to a LI drop of 10 Ω and were stopped when a maximum cut-off LI drop of Results 153 consecutive patients (61% paroxysmal AF, 39% persistent AF) were enrolled in the study. 3556 point-by-point first-pass RF applications of >10 s duration were performed around PVs. The mean LI drop was 13 ± 8Ω, the mean τ was 18.7 ± 13s and the median LI drop/τ was 0.67 [QI-QIII, 0.37 – 1.17] Ω/s. Both absolute drops in LI and LI drop/τ were greater at successful ablation sites (n = 3122, 88%) than at ineffective ablation sites (n = 434, 12%) (14 ± 8Ω vs 6 ± 4Ω, p Conclusions The magnitude and time-course of the LI drop during RF delivery were associated with effective lesion formation. This ablation strategy for PVI guided by LI technology proved safe and effective, and resulted in a very low rate of AF recurrence over 1-year follow-up.

Background: Current guidelines recommend avoiding apical left ventricular (LV) pacing for cardiac resynchronization therapy (CRT). Aims: We investigated the feasibility of nonapical pacing with the current quadripolar LV lead technology. Methods: We analyzed consecutive patients who received CRT with an LV quadripolar lead. The post­­implantation position of each electrode of the LV lead was designated as basal, mid, or apical. The pacing capture threshold (PCT) and phrenic nerve stimulation (PNS) threshold were assessed for each electrode. Results: We enrolled 168 patients. A total of 8 CRT defibrillators were from Biotronik (with Sentus OTW QP leads), 98 were from Boston Scientific (with 21 Acuity X4 Spiral and 77 Acuity X4 Straight leads), and 62 from St. Jude Medical (with Quartet leads). The median (interquartile range) number of electrodes at nonapical segments per patient was 3 (1–4) with Biotronik Sentus leads, 4 (3–4) with spiral ­design Boston Scientific leads, 4 (3–4) with straight Boston Scientific leads, and 3 (3–4) with St. Jude Medical Quartet leads (P = 0.045). Three patients (38%) with Biotronik Sentus leads, 21 (100%) with spiral ­design Boston Scientific leads, 69 (90%) with straight ­design Boston Scientific leads, and 49 (79%) with St. Jude Medical Quartet leads (P < 0.001) had at least 1 electrode located at nonapical segments linked with a PNS ­PCT safety margin of more than 2 V. During the 6­month follow ­up, PNS was detected in 4 patients and was eliminated with reprogramming. No significant changes in PCT were detected during follow ­up. Conclusions: Quadripolar leads allowed nonapical pacing with acceptable electrical parameters in the majority of CRT recipients, although differences were found among the currently available devices.

Introduction The effectiveness of bowel cleansing is a key element for high-quality colonoscopy. Recently, a 1 L polyethylene glycol plus ascorbate (PEG-ASC) solution has been introduced, but effectiveness and safety of this preparation have not been assessed in IBD patients. This study aims to evaluate effectiveness and safety of 1 L PEG-ASC solution in patients with IBD compared to controls. Methods We retrospectively analysed prospectively collected data on a cohort of 411 patients performing a colonoscopy after preparation with 1 L PEG-ASC, consecutively enrolled in 5 Italian centres. Results Overall, 185/411 (45%) were patients with IBD and 226/411 (55%) served as controls. A significantly higher cleansing success was achieved in IBD patients (92.9% vs 85.4%, p = 0.02). The multiple regression model showed that presence of IBD (OR=2.514, 95%CI=1.165–5.426; P = 0.019), lower age (OR=0.981, 95%CI=0.967–0.996; P = 0.014), split preparation (OR=2.430, 95%CI=1.076–5.492; P = 0.033), absence of diabetes (OR=2.848, 95%CI=1.228–6.605; P = 0.015), and of chronic constipation (OR=3.350, 95%CI=1.429–7.852; P = 0.005), were independently associated with cleansing success. The number of treatment-emergent adverse events (TEAEs) (51 vs 62%, p = 0.821), and of patients with TEAEs (22.2% vs 21.2%, p = 0.821), were similar in IBD patients and in controls, respectively. Conclusions Results from this study support the effectiveness and safety of 1 L PEG-ASC solution in IBD patients, which may improve the definition of endoscopic outcomes both in Crohn’s disease and ulcerative colitis.

Background: The presence of residual disease after initial treatment in small cell lung cancer (SCLC) influences prognosis and impacts patient management. To date, few data exist on the value of fluorine-18-fluorodeoxyglucose ([F]FDG)-PET/computed tomography (CT) in SCLC at restaging. Therefore, in restaging patients with SCLC, we aimed to (a) evaluate the prognostic value yielded by [F]FDG-PET/CT and (b) assess the diagnostic agreement between [F]FDG-PET/CT and contrast-enhanced computed tomography (ceCT). Patients and methods: From a multicenter database, we evaluated 164 patients with SCLC who underwent [F]FDG-PET/CT for restaging purposes. PET scans were evaluated visually to identify the presence of recurrence. For each patient, the maximum and the mean standardized uptake value (SUVmax and SUVmean, respectively), metabolic tumor volume, and total lesion glycolysis were calculated, taking into account the lesion with the highest [F]FDG uptake (namely, the index lesion) in the local recurrences, lymph node involvement, and distant metastasis categories. Kaplan-Meier curves were computed to assess the effects of [F]FDG-PET/CT findings on overall survival (OS) and progression-free survival. Furthermore, the agreement between PET/CT and ceCT in detecting metastases was evaluated in 119 patients on a patient-based analysis (Cohen's κ; P < 0.05). Results: The presence of metastatic lesions at [F]FDG-PET/CT was associated with a significantly shorter OS (P = 0.039) and progression-free survival (P < 0.001). Higher SUVmax showed a trend toward a shorter OS (P = 0.065). The K-agreement between ceCT and PET/CT in recurrent SCLC was 0.37 (P < 0.001). PET/CT and ceCT showed the same number of lesions in 52 (43.7%) patients, whereas PET/CT detected additional lesions in 35 (29.4%) patients. Conclusion: Detection of metastatic lesions at restaging by [F]FDG-PET/CT can predict a higher rate of progression and negatively influence OS in patients with SCLC. [F]FDG-PET/CT and ceCT seem to be complementary imaging modalities in patients with metastatic SCLC.

Background and purpose: Biomarkers support the aetiological diagnosis of neurocognitive disorders in vivo. Incomplete evidence is available to drive clinical decisions; available diagnostic algorithms are generic and not very helpful in clinical practice. The aim was to develop a biomarker-based diagnostic algorithm for mild cognitive impairment patients, leveraging on knowledge from recognized national experts. Methods: With a Delphi procedure, experienced clinicians making variable use of biomarkers in clinical practice and representing five Italian scientific societies (neurology – Società Italiana di Neurologia per le Demenze; neuroradiology – Associazione Italiana di Neuroradiologia; biochemistry – Società Italiana di Biochimica Clinica; psychogeriatrics – Associazione Italiana di Psicogeriatria; nuclear medicine – Associazione Italiana di Medicina Nucleare) defined the theoretical framework, relevant literature, the diagnostic issues to be addressed and the diagnostic algorithm. An N–1 majority defined consensus achievement. Results: The panellists chose the 2011 National Institute on Aging and Alzheimer's Association diagnostic criteria as the reference theoretical framework and defined the algorithm in seven Delphi rounds. The algorithm includes baseline clinical and cognitive assessment, blood examination, and magnetic resonance imaging with exclusionary and inclusionary roles; dopamine transporter single-photon emission computed tomography (if no/unclear parkinsonism) or metaiodobenzylguanidine cardiac scintigraphy for suspected dementia with Lewy bodies with clear parkinsonism (round VII, votes(yes-no-abstained): 3-1-1); 18F-fluorodeoxyglucose positron emission tomography for suspected frontotemporal lobar degeneration and low diagnostic confidence of Alzheimer’s disease (round VII, 4-0-1); cerebrospinal fluid for suspected Alzheimer’s disease (round IV, 4-1-0); and amyloid positron emission tomography if cerebrospinal fluid was not possible/accepted (round V, 4-1-0) or inconclusive (round VI, 5-0-0). Conclusions: These consensus recommendations can guide clinicians in the biomarker-based aetiological diagnosis of mild cognitive impairment, whilst guidelines cannot be defined with evidence-to-decision procedures due to incomplete evidence.

The VASOTENS Registry is an international telehealth-based repository of 24-hour ambulatory blood pressure monitorings (ABPM) obtained through an oscillometric upper-arm BP monitor allowing combined estimation of some vascular biomarkers. The present paper reports the results obtained in 1200 participants according to different categories of CV risk. Individual readings were averaged for each recording and 24-hour mean of brachial and aortic systolic (SBP) and diastolic blood pressure (DBP), pulse wave velocity (PWV), and augmentation index (AIx) obtained. Peripheral and central BP, PWVand AIx values were increased in older participants (SBP only) and in case of hypertension (SBP and DBP). BP was lower and PWVand AIx higher in females. PWV was increased and BP unchanged in case of metabolic syndrome. Our results suggest that ambulatory pulse wave analysis in a daily life setting may help evaluate vascular health of individuals at risk for CV disease.

Background MS is a neurodegenerative autoimmune disease resulting from a complex interaction of genetic and environmental factors. Among these, vitamin D and genetic variants associated with vitamin D-metabolism gain great attention. The aim of our study was to assess five SNPs in NADSYN1 and CYP2R1 genes in relation to serum 25-OH-vitamin D3 levels in MS patients and controls. Methods 25-OH-vitamin D3 levels and genotyping of CYP2R1- and NADSYN1-SNPs were investigated both in MS patients and in healthy controls. Results The analysis revealed lower 25-OH-vitamin D3 concentrations in MS patients than in controls and an association of rs10766197 CYP2R1 SNP with MS risk. After stratifying MS patients according to gender, we found that the minor allele A of rs10766197 had a higher frequency in men in comparison to women affected by MS. Additionally, the presence of allele A in men was associated with disease progression, assessed by EDSS and MSSS scores. Conclusion The findings of our study open new perspectives for a role of CYP2R1 in both risk and progression of MS, with sex-related differences.

Aim To investigate the relationships between amyloid burden in brain and the age of onset of Alzheimer's disease. Materials and methods We examined 60 patients with clinical diagnosis of Alzheimer's disease. Of them, 22 were early-onset of Alzheimer's disease and 38 were late-onset of Alzheimer's disease. All of them underwent a brain PET scan 90 minutes after the injection of 4-[(E)-2-[4-[2-[2-(2-fluoranylethoxy)ethoxy]ethoxy]phenyl]ethenyl]-N-methylaniline ([F] FBB); 300 ± 10 MBq). Relationships between amyloid burden in brain and age of onset of Alzheimer's disease were assessed by means of statistical parametric mapping version 12. Results There were no significant differences [F] FBB uptake between early-onset of Alzheimer's disease and late-onset of Alzheimer's disease patients. Conclusion In our study group, the age of onset is not related to brain amyloid burden in Alzheimer's disease patients.

Background and Aims: The Diverticular Inflammation and Complication Assessment (DICA) endoscopic classification of diverticulosis and diverticular disease (DD) is currently available. It scores severity of the disease as DICA 1, DICA 2 and DICA 3. Our aim was to assess the agreement on this classification in an international endoscopists community setting. Methods: A total of 96 doctors (82.9% endoscopists) independently scored a set of DD endoscopic videos. The percentages of overall agreement on DICA score and a free-marginal multirater kappa (κ) coefficient were reported as statistical measures of interrater agreement. Results: Overall agreement in using DICA was 91.8% with a free-marginal kappa of 88% (95% CI 80-95). The overall agreement levels were: DICA 1, 85.2%; DICA 2, 96.5%; DICA 3, 99.5%. The free marginal κ was: DICA 1 = 0.753, DICA 2 = 0.958, DICA 3 = 0.919. The agreement about the main endoscopic items was 83.4% (k 67%) for diverticular extension, 62.6% (k 65%) for number of diverticula for each district, 86.8% (k 82%) for presence of inflammation, and 98.5 (k 98%) for presence of complications. Conclusions: The overall interrater agreement in this study ranges from good to very good. DICA score is a simple and reproducible endoscopic scoring system for diverticulosis and DD.

Metastatic castration-resistant prostate cancer (mCRPC) represents a condition of progressive disease in spite of androgen deprivation therapy (ADT), with a broad spectrum of manifestations ranging from no symptoms to severe debilitation due to bone or visceral metastatization. The management of mCRPC has been profoundly modified by introducing novel therapeutic tools such as antiandrogen drugs (i.e., abiraterone acetate and enzalutamide), immunotherapy through sipuleucel-T, and targeted alpha therapy (TAT). This variety of approaches calls for unmet need of biomarkers suitable for patients’ pre-treatment selection and prognostic stratification. In this scenario, imaging with positron emission computed tomography (PET/CT) presents great and still unexplored potential to detect specific molecular and metabolic signatures, some of whom, such as the prostate specific membrane antigen (PSMA), can also be exploited as therapeutic targets, thus combining diagnosis and therapy in the so-called “theranostic” approach. In this review, we performed a web-based and desktop literature research to investigate the prognostic and theranostic potential of several PET imaging probes, such as 18F-FDG, 18F-choline and 68Ga-PSMA-11, also covering the emerging tracers still in a pre-clinical phase (e.g., PARP-inhibitors’ analogs and the radioligands binding to gastrin releasing peptide receptors/GRPR), highlighting their potential for defining personalized care pathways in mCRPC

Aminoacyl-tRNA synthetases (ARSs) are crucial enzymes for protein translation. Mutations in genes encoding ARSs are associated with human disease. Tyrosyl-tRNA synthetase is encoded by YARS which is ubiquitously expressed and implicated in an autosomal dominant form of Charcot-Marie-Tooth and autosomal recessive YARS-related multisystem disease. We report on a former 34-week gestational age male who presented at 2 months of age with failure to thrive (FTT) and cholestatic hepatitis. He was subsequently diagnosed with hyperinsulinemic hypoglycemia with a negative congenital hyperinsulinism gene panel and F-DOPA positron-emission tomography (PET) scan that did not demonstrate a focal lesion. Autopsy findings were notable for overall normal pancreatic islet size and morphology. Trio whole exome sequencing identified a novel homozygous variant of uncertain significance in YARS (c.611A > C, p.Tyr204Cys) with each parent a carrier for the YARS variant. Euglycemia was maintained with diazoxide (max dose, 18 mg/kg/day), and enteral dextrose via gastrostomy tube (G-Tube). During his prolonged hospitalization, the patient developed progressive liver disease, exocrine pancreatic insufficiency, acute renal failure, recurrent infections, ichthyosis, hematologic concerns, hypotonia, and global developmental delay. Such multisystem features have been previously reported in association with pathogenic YARS mutations. Although hypoglycemia has been associated with pathogenic YARS mutations, this report provides more conclusive data that a YARS variant can cause hyperinsulinemic hypoglycemia. This case expands the allelic and clinical heterogeneity of YARS-related disease. In addition, YARS-related disease should be considered in the differential of hyperinsulinemic hypoglycemia associated with multisystem disease.

BACKGROUND The management of patients with unprotected left main (LM) coronary artery disease remains challenging, with recent data casting a shadow of doubt on the safety of percutaneous coronary intervention. We aimed at describing the features of patients undergoing myocardial perfusion imaging (MPI) subsequently found to have LM disease. METHODS We queried our institutional database for subjects without prior revascularization or myocardial infarction (MI), who had undergone MPI followed by invasive coronary angiography within 6 months, comparing those with evidence of angiographically significant LM disease (i.e. diameter stenosis ≥50%) to those without significant coronary artery disease (CAD), or those with CAD not involving LM. Baseline, stress and imaging features were systematically collected and analyzed, and clinical outcomes (death, myocardial infarction, revascularization) sought. RESULTS We included a total of 74 patients with LM disease, which were compared with 70 without CAD, and 920 with significant CAD not involving LM. MPI was remarkably safe in all subjects, and significant differences were found for several features, but particularly so for ST change, rate pressure product, and left ventricular ejection fraction (all P

Neuroblastoma (NB) represents the most common extracranial tumor of childhood. Prognosis is quite variable, ranging from spontaneous regression to aggressive behavior with wide metastatization, high mortality, and limited therapeutic options. Radiotheranostics combines a radiopharmaceutical pair in a unique approach, suitable both for diagnosis and therapy. For many years, metaiodobenzylguanidine (MIBG), labeled with 123I for imaging or 131I for therapy, has represented the main theranostic agent in NB, since up to 90% of NB incorporates the aforementioned radiopharmaceutical. In recent years, novel theranostic agents hold promise in moving the field of NB radiotheranostics forward. In particular, SarTATE, consisting of octreotate targeting somatostatin receptors, has been applied with encouraging results, with 64Cu-SARTATE being used for disease detection and with 67Cu-SARTATE being used for therapy. Furthermore, recent evidence has highlighted the potential of targeted alpha therapy (TAT) for treating cancer by virtue of alpha particles’ high ionizing density and high probability of killing cells along their track. On this path, 211At-astatobenzylguanidine (MABG) has been developed as a potential agent for TAT and is actually under evaluation in preclinical NB models. In this review, we performed a web-based and desktop literature research concerning radiotheranostic approaches in NB, covering both the radiopharmaceuticals already implemented in clinical practice (i.e.,123/1311-MIBG) and those still in a preliminary or preclinical phase.

Vitamin D deficiency is associated with increased risks of mortality in people with chronic kidney disease. The benefits and harm of vitamin D supplementation on cardiovascular outcomes and mortality are unknown. We aimed to assess the effectiveness of calcifediol in reducing mortality in patients with vitamin D insufficiency on hemodialysis compared to no additional therapy. A phase III, multicenter, randomized, open-label trial was conducted including 284 adults with vitamin D insufficiency undergoing hemodialysis who were randomly assigned to receive oral calcifediol or standard care for 24 months. Two hundred eighty-four participants were enrolled (143 assigned to the calcifediol group and 141 to the no additional therapy group). The primary outcome (mortality) occurred in 34 and 31 participants in the calcifediol and control group, respectively [hazard ratio (HR) 1.03; 95% confidence interval (CI) 0.63–1.67]. Calcifediol had no detectable effects on cardiovascular death (HR 1.06; 95% CI 0.41–2.74), non-cardiovascular death (HR 1.13; 95% CI 0.62–2.04), nonfatal myocardial infarction (HR 0.20; 95% CI 0.02–1.67) or nonfatal stroke (HR could not be estimated). The incidence of hypercalcemia and hyperphosphatemia was similar between groups. None of the participants underwent parathyroidectomy. In adults treated with hemodialysis and who had vitamin D insufficiency, calcifediol supplementation for 24 months had inconclusive effects on mortality and cardiovascular outcomes. NCT01457001

Background: our aim was to assess the diagnostic performance and clinical impact of 18F-FDG PET/CT in patients with differentiated thyroid carcinoma (DTC), previously treated with surgery and radioiodine therapy (RAI). Methods: patients subjected to 18F-FDG PET/CT for suspected DTC recurrence in three Italian nuclear medicine units were evaluated. Two different clinical settings were identified: clinical setting 1 included patients (n = 40) that were enrolled according to the American Thyroid Association guidelines (i.e., negative 1311-WBS and Tg level > 10 ng/mL); and clinical setting 2, that encompassed subjects (n = 26) with serum Tg ≤ 10 ng/mL but morphological findings suspected of relapse. PET/CT’s impact was scored as significant if it provided an indication for surgery, or led to a novel therapeutic decision. Results: In total, 51/66 patients (77.3%) were 18F-FDG positive, while 15 (22.7%) were negative. PET/CT showed an overall sensitivity and specificity of 84.4% and 75%, respectively. Sensitivity was higher in clinical setting 1 (89.1%) as compared to clinical setting 2 (76.1%), although this difference was not statistically significant (p = 0.83). PET/CT influenced clinical management in 28 cases (42.4%), without a significant difference between the 2 groups of patients (p = 0.6). Conclusions: our preliminary data, although limited by the retrospective nature of the study and possible selection bias, suggest that 18F-FDG PET/CT may be utilized for the detection of DTC recurrence in different clinical settings, with a meaningful impact on clinical management.

Background Fluoroscopy is commonly used in cryoballoon catheter ablation for pulmonary vein (PV) isolation procedures in patients with atrial fibrillation (AF). Purpose The purpose of this study was to verify the feasibility of a new dielectric imaging system in reducing the radiation exposure during cryoballoon ablation in patients with AF. Methods We enrolled 40 consecutive patients with paroxysmal AF: 20 patients underwent the procedure under fluoroscopy guidance before the new system introduction, while 20 patient underwent the procedure under fluoroscopy and a new dielectric imaging system guidance with its occlusion tool software. After transseptal access a detailed image reconstruction of left atrium and PVs was achieved with an octapolar circular mapping catheter and the cryoablation was performed with a cryoballoon catheter. Results Total time of the procedure was comparable between the two groups (90.15±28.67 vs 80.77±17.17 using the dielectric imaging system, p=0.34), while fluoroscopy time was significantly lower in the group using the new dielectric imaging system (16.92±8.96 vs 5.54±2.06, p Conclusion This is the first study that demonstrates the feasibility of a reduce fluoroscopy workflow using the novel dielectric imaging system in a cryoballoon procedure. Funding Acknowledgement Type of funding source: None