What is the additional value of electronic medical records for drug safety signal detection? The experience of eu-adr project

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A parathyroid carcinoma within a cold thyroid nodule

We report the case of a 71-year-old woman who was referred to our institute with a solid nodule in the right thyroid lobe and hypercalcemia. Ultrasound revealed a well-vascularized right thyroid nodule that was identified as a cold area by 99mTc-sodium pertechnetate scan. Fine-needle aspiration showed a follicular lesion and blood tests revealed hypercalcemia and hyperparathyroidism. A 99mTc-methoxyisobutylisonitrile (99mTc-Sestamibi) scan was subsequently performed revealing a focal area of increased uptake in the right thyroid lobe, within the cold area detected by the thyroid scan. A right emithyroidectomy and right superior and inferior parathyroidectomy was performed and histopathological examination showed a parathyroid carcinoma (immunohistochemistry positive for PTH and chromogranin A, Ki-67 10%) associated with follicular hyperplasia

[18F] FDG uptake: pay attention to candies

[18F]Fluorodeoxyglucose ([18F]FDG) is a positron emission radiotracer whose biodistribution is similar to glucose. The similar biodistribution of [18F]FDG and glucose in the human body requires a fasting condition for at least six hours prior to performing a [18F]FDG positron emission tomography ([18F]FDG PET) study

Freeze-out configuration properties in the 197Au + 197Au reaction at 23 AMeV

Data from the experiment on the 197Au + 197Au reaction at 23 AMeV are analyzed with an aim to find signatures of exotic nuclear configurations such as toroid-shaped objects. The experimental data are compared with predictions of the ETNA code dedicated to look for such configurations and with the QMD model. A novel criterion of selecting events possibly resulting from the formation of exotic freeze-out configurations, "the efficiency factor", is tested. Comparison between experimental data and model predictions may indicate for the formation of flat/toroidal nuclear systems

Post-Marketing Surveillance of CAR-T-Cell Therapies: Analysis of the FDA Adverse Event Reporting System (FAERS) Database

Introduction As chimeric antigen receptor T-cell therapies are becoming increasingly available in the armamentarium of the hematologist, there is an emerging need to monitor post-marketing safety. Objective We aimed to better characterize their safety profile by focusing on cytokine release syndrome and identifying emerging signals. Methods We queried the US Food and Drug Administration Adverse Event Reporting System (October 2017-September 2020) to analyze suspected adverse drug reactions to tisagenlecleucel (tisa-cel) and axicabtagene ciloleucel (axi-cel). Disproportionality analyses (reporting odds ratio) were performed by comparing chimeric antigen receptor T-cell therapies with (a) all other drugs (reference group 1) and (b) other onco-hematological drugs with a similar indication, irrespective of age (reference group 2), or (c) restricted to adults (reference group 3). Notoriety was assessed through package inserts and risk management plans. Adverse drug reaction time to onset and cytokine release syndrome features were investigated. Results Overall, 3225 reports (1793 axi-cel; 1433 tisa-cel) were identified. The reported toxicities were mainly: cytokine release syndrome (52.2%), febrile disorders (27.7%), and neurotoxicity (27.2%). Cytokine release syndrome and neurotoxicity were often co-reported and 75% of the events occurred in the first 10 days. Disproportionalities confirmed known adverse drug reactions and showed unexpected associations: for example, axi-cel with cardiomyopathies (reporting odds ratio = 2.3; 95% confidence interval 1.2-4.4) and gastrointestinal perforations (2.9; 1.2-7.3), tisa-cel with hepatotoxicity (2.5; 1.1-5.7) and pupil disorders (15.3; 6-39.1). Conclusions Our study confirms the well-known adverse drug reactions and detects potentially emerging safety issues specific for each chimeric antigen receptor T-cell therapy, also providing insights into a stronger role for tisa-cel in inducing some immunodeficiency-related events (e.g., hypogammaglobulinemia, infections) and coagulopathies, and for axi-cel in neurotoxicity

Growth hormone therapy and respiratory disorders: Long-term follow-up in PWS children

Context: Adenotonsillar tissue hypertrophy and obstructive sleep apnea have been reported during short-term GH treatment in children with Prader-Willi syndrome (PWS). Objective: We conducted an observational study to evaluate the effects of long-term GH therapy on sleep-disordered breathing and adenotonsillar hypertrophy in children with PWS. Design: This was a longitudinal observational study. PatientsandMethods:Weevaluated 75 children with genetically confirmedPWS,ofwhom50 fulfilled the criteria and were admitted to our study. The patients were evaluated before treatment (t0), after 6 weeks (t1), after 6 months (t2), after 12 months (t3), and yearly (t4-t6) thereafter, for up to 4 years of GH therapy. The central apnea index, obstructive apnea hypopnea index (OAHI), respiratory disturbance index, and minimal blood oxygen saturation were evaluated overnight using polysomnography. We evaluated the adenotonsillar size using a flexible fiberoptic endoscope. Results: The percentage of patients with an OAHI of 1 increased from 3 to 22, 36, and 38 at t1, t4, and t6, respectively (2 12.2; P .05). We observed a decrease in the respiratory disturbance indexfrom1.4 (t0) to 0.8 (t3) (P.05)andthe centralapneaindexfrom1.2 (t0) to 0.1 (t4) (P.0001). We had to temporarily suspend treatment for 3 patients at t1, t4, and t5 because of severe obstructive sleep apnea. The percentage of patients with severe adenotonsillar hypertrophy was significantly higher at t4 and t5 than at t0. The OAHI directly correlated with the adenoid size (adjusted for age) (P .01) but not with the tonsil size and IGF-1 levels. Conclusion: Long-termGHtreatment in patients withPWSis safe; however,werecommend annual polysomnography and adenotonsillar evaluation

Evidence for a Novel Reaction Mechanism of a Prompt Shock-Induced Fission Following the Fusion of 78Kr and 40Ca Nuclei at E/A =10 MeV

An analysis of experimental data from the inverse-kinematics ISODEC experiment on 78Kr+40Ca reaction at a bombarding energy of 10 AMeV has revealed signatures of a hitherto unknown reaction mechanism, intermediate between the classical damped binary collisions and fusion-fission, but also substantially different from what is being termed in the literature as fast fission or quasi fission. These signatures point to a scenario where the system fuses transiently while virtually equilibrating mass asymmetry and energy and, yet, keeping part of the energy stored in a collective shock-imparted and, possibly, angular momentum bearing form of excitation. Subsequently the system fissions dynamically along the collision or shock axis with the emerging fragments featuring a broad mass spectrum centered around symmetric fission, relative velocities somewhat higher along the fission axis than in transverse direction, and virtually no intrinsic spin. The class of massasymmetric fission events shows a distinct preference for the more massive fragments to proceed along the beam direction, a characteristic reminiscent of that reported earlier for dynamic fragmentation of projectile-like fragments alone and pointing to the memory of the initial mass and velocity distribution.Comment: 5 PAGES, 6 FIGURE

Poor health related quality of life and unhealthy lifestyle habits in weight-loss treatment-seeking youth

Obesity is associated with unhealthy lifestyle behaviors and poor Health Related Quality of Life (HRQOL). The cumulative effect of lifestyle behaviors on HRQOL has been demonstrated in chronically ill adolescents, but not in adolescents with obesity. The present study aimed to assess the association between HRQOL and adherence to the Mediterranean Diet (MD) and/or low levels of physical activity (PA) in a large sample of outpatient adolescents with overweight or obesity seeking weight loss treatment. Four-hundred-twenty participants were enrolled from 10 Italian outpatient clinics. The demographics and anthropometric features, KIDMED scores, and exercise levels of the participants were collected, together with parental features. The HRQOL was assessed by the Pediatric Quality of Life Inventory (PedsQL™), Adolescents Version 4.0. PedsQL total score and functioning subscales were lower in adolescents who reported one or two unhealthy habits. Compared with the high/intermediate groups, the risk of low HRQOL was twice as high for each unit increase in BMI SDS, while the percentage was reduced by 12.2% for every unit increase in the KIDMED score and by 32.3% for each hour increase of exercise. The clustering of these two unhealthy behaviors conferred a 120% higher risk of low HRQOL. Similarly, adolescents displaying better diet quality and/or a physically more active lifestyle have better physical and psychological functioning. Further studies are needed to disclose whether these characteristics may be predictive of better adherence to weight loss treatment

Poor health related quality of life and unhealthy lifestyle habits in weight-loss treatment-seeking youth

Obesity is associated with unhealthy lifestyle behaviors and poor Health Related Quality of Life (HRQOL). The cumulative effect of lifestyle behaviors on HRQOL has been demonstrated in chronically ill adolescents, but not in adolescents with obesity. The present study aimed to assess the association between HRQOL and adherence to the Mediterranean Diet (MD) and/or low levels of physical activity (PA) in a large sample of outpatient adolescents with overweight or obesity seeking weight loss treatment. Four-hundred-twenty participants were enrolled from 10 Italian outpatient clinics. The demographics and anthropometric features, KIDMED scores, and exercise levels of the participants were collected, together with parental features. The HRQOL was assessed by the Pediatric Quality of Life Inventory (PedsQL™), Adolescents Version 4.0. PedsQL total score and functioning subscales were lower in adolescents who reported one or two unhealthy habits. Compared with the high/intermediate groups, the risk of low HRQOL was twice as high for each unit increase in BMI SDS, while the percentage was reduced by 12.2% for every unit increase in the KIDMED score and by 32.3% for each hour increase of exercise. The clustering of these two unhealthy behaviors conferred a 120% higher risk of low HRQOL. Similarly, adolescents displaying better diet quality and/or a physically more active lifestyle have better physical and psychological functioning. Further studies are needed to disclose whether these characteristics may be predictive of better adherence to weight loss treatment