Thomas Daniel

Background: Subclinical hyperthyroidism grade 1 (SCH G1, TSH > 0.1 mU/L) is common in patients with thyroid unifocal autonomy (UFA) and associated with cardiovascular risks and increased mortality. While ¹³¹I radioiodine therapy (¹³¹I-RIT) effectively treats UFA, it frequently induces hypothyroidism, partly due to extra-nodular absorbed dose (AD) enhanced by residual TSH stimulation. Objective: We hypothesized that short-term LT3-induced TSH suppression at the time of RIT would promote long-term euthyroidism. Patients and Methods: A retrospective study was conducted on 95 UFA patients with SCH G1 (2001–2024). Patients underwent baseline and post-LT3 thyroid scintigraphy, and then received ¹³¹I-RIT with individualized dosimetry. Long-term bioclinical follow-up was achieved. Results: Short-term low-dose LT3 suppression caused no adverse events and significantly reduced TSH (0.45 to 0.047 mU/L). Whole-gland ¹²³I uptake decreased moderately (11.0 to 8.4%), while extra-nodular lobe uptake dropped markedly (1.77 to 0.73%) (all p < 0.0001). This focused activity on the UFA (2.5-fold increase), maintaining mean UFA AD (about 260 Gy) but reducing extra-nodular AD (61 to 37 Gy, p < 0.0001). Despite low ¹³¹I doses (mean 181 MBq), a dose–response relationship was observed: higher AD correlated with greater nodular lobe volume reduction (p < 0.033). At the 88-month follow-up, 93% of patients achieved normal thyroid function; one had persistent SCH G1, two were borderline hypothyroid, and two required LT4. Conclusions: ¹³¹I-RIT under brief LT3-induced TSH suppression induces sustained euthyroidism in SCH G1 with UFA. This simple, low-risk strategy reduces radioprotection concerns and is under evaluation to determine cardiovascular benefits.

Background: [⁶⁸Ga]Ga-PentixaFor is a promising radiotracer for positron emission tomography imaging of several human tumors overexpressing the chemokine receptor-4 (CXCR4). CXCR4 overexpression has been demonstrated in patients with hematologic malignancies, solid cancers, as well as cardiovascular pathologies of inflammatory origins. However, its radio synthesis is not yet fully developed in France, and existing methods do not use our type of synthesis module. Therefore, we aimed at developing a [⁶⁸Ga]Ga-PentixaFor synthesis with Gaia/Luna Elysia-Raytest module to use it in clinical purpose. Results: 12 syntheses were carried out by varying the temperature conditions and radiolabeling times, and led to choose specific labelling conditions with the Gaia/Luna Elysia-Raytest module: 97 °C, 4 min. The mean synthesis time of the 3 validation runs under good manufacturing practice (GMP) was 24 min 27 s (± 8 s), and the mean radiochemical yield was 87.0% [standard deviation (SD) 6.67%]. Different quality control parameters were also evaluated in accordance with European Pharmacopeia: radiochemical and radionuclidic purity, pH, sterility, stability and endotoxins levels. The average radiochemical purity was 99.1% (SD 0.25%) assessed by instant thin layer chromatography and 99.8% (SD 0.092%) assessed by high pressure liquid chromatography. average [⁶⁸Ge] breakthrough was 1.48 × 10^–5%, under the recommended level of 0.001%. We assessed the stability of the radiotracer up to 4 h at room temperature (no augmentation of the [⁶⁸Ga] chloride in the final product, i.e. radiochemical purity (RCP) > 98.5%). The endotoxins levels were < 5 EU/mL, and the pH was 6.5 (same for the three syntheses). Conclusion: The [⁶⁸Ga]Ga-PentixaFor synthesis process developed on the Gaia/Luna Elysia-Raytest module has fulfilled all acceptance criteria for injectable radiopharmaceutical products regarding the European Pharmacopeia. The radiochemical purity, stability, efficacy, as well as the microbiological quality of the three GMP batches were found to be good. The robustness of the synthesis process may be suitable for multi-dose application in clinical settings.

Background [⁶⁸Ga]Ga-PentixaFor is a promising radiotracer for positron emission tomography imaging of several human tumors overexpressing the chemokine receptor-4 (CXCR4). CXCR4 overexpression has been demonstrated in patients with hematologic malignancies, solid cancers, as well as cardiovascular pathologies of inflammatory origins. However, its radio synthesis is not yet fully developed in France, and existing methods do not use our type of synthesis module. Therefore, we aimed at developing a [⁶⁸Ga]Ga-PentixaFor synthesis with Gaia/Luna Elysia-Raytest module to use it in clinical purpose. Results 12 syntheses were carried out by varying the temperature conditions and radiolabeling times, and led to choose specific labelling conditions with the Gaia/Luna Elysia-Raytest module: 97°Celsius, 4 minutes. The mean 3 Good Manufacturing Practice (GMP)-conditions synthesis time was 24 min 27 s (+/- 8 s), and the mean radiolabeling efficiency was 86.96% (Standard deviation (SD) 6.67%). Different quality control parameters were also evaluated in accordance with European Pharmacopeia: radiochemical and radionuclidic purity, pH, sterility, stability and endotoxins levels. The average radiochemical purity was 99.09% (SD 0.25%) assessed by Instant Thin Layer Chromatography and 99.82% (SD 0.092%) assessed by High Pressure Liquid Chromatography. Average 68-germanium breakthrough was 0.0000148%, under the recommended level of 0.001%. We assessed the stability of the radiotracer up to 4 hours at room temperature (no augmentation of the ^[68Ga] chloride in the final product, i.e. radiochemical purity (RCP) > 98.5%). The endotoxins levels were < 5.00 EU/mL, and the pH was 6.5 (same for the three syntheses). Conclusion The [⁶⁸Ga]Ga-PentixaFor synthesis process developed on the Gaia/Luna Elysia-Raytest module has fulfilled all acceptance criteria for injectable radiopharmaceutical products regarding the European Pharmacopeia. The radiochemical purity, stability, efficacy, as well as the microbiological quality of the three GMP batches were found to be good. The robustness of the synthesis process may be suitable for multi-dose application in clinical settings.

Background: Access to accurate information in health care is a key point for caregivers to avoid medication errors, especially with the reorganization of staff and drug circuits during health crises such as the COVID‑19 pandemic. It is, therefore, the role of the hospital pharmacy to answer caregivers’ questions. Some may require the expertise of a pharmacist, some should be answered by pharmacy technicians, but others are simple and redundant, and automated responses may be provided. Objective: We aimed at developing and implementing a chatbot to answer questions from hospital caregivers about drugs and pharmacy organization 24 hours a day and to evaluate this tool. Methods: The ADDIE (Analysis, Design, Development, Implementation, and Evaluation) model was used by a multiprofessional team composed of 3 hospital pharmacists, 2 members of the Innovation and Transformation Department, and the IT service provider. Based on an analysis of the caregivers’ needs about drugs and pharmacy organization, we designed and developed a chatbot. The tool was then evaluated before its implementation into the hospital intranet. Its relevance and conversations with testers were monitored via the IT provider’s back office. Results: Needs analysis with 5 hospital pharmacists and 33 caregivers from 5 health services allowed us to identify 7 themes about drugs and pharmacy organization (such as opening hours and specific prescriptions). After a year of chatbot design and development, the test version obtained good evaluation scores: its speed was rated 8.2 out of 10, usability 8.1 out of 10, and appearance 7.5 out of 10. Testers were generally satisfied (70%) and were hoping for the content to be enhanced. Conclusions: The chatbot seems to be a relevant tool for hospital caregivers, helping them obtain reliable and verified information they need on drugs and pharmacy organization. In the context of significant mobility of nursing staff during the health crisis due to the COVID-19 pandemic, the chatbot could be a suitable tool for transmitting relevant information related to drug circuits or specific procedures. To our knowledge, this is the first time that such a tool has been designed for caregivers. Its development further continued by means of tests conducted with other users such as pharmacy technicians and via the integration of additional data before the implementation on the 2 hospital sites.

BACKGROUND Access to accurate information in health is a key point for caregivers to avoid medication errors, especially with the reorganization of staff and drugs circuits during health crises such as COVID 19. It is therefore the role of the hospital pharmacy to answer caregivers’ questions. Some may require the expertise of a pharmacist, some should be answered by pharmacy technicians, but others are simple and redundant, and automated responses may be given. OBJECTIVE We aimed at developing and implementing a chatbot to answer questions from hospital caregivers, 24 hours a day, about drugs and pharmacy organization, and evaluated this tool. METHODS The ADDIE model: Analysis, Design, Development, Implementation, Evaluation, was used by a multi-professional team composed of 3 hospital pharmacists, 2 members of the Innovation and Transformation Department, and the Information Technology (IT) service provider. Based on an analysis of the caregivers’ needs about drugs and pharmacy organization, we designed and developed a chatbot. The tool was then evaluated before the implementation into the hospital intranet. Its relevance and conversations with testers were monitored via the IT provider’s back office. RESULTS Needs analysis with 5 hospital pharmacists and 33 caregivers from 5 health services allowed us to identify 7 themes about drugs and pharmacy organization (such as opening hours and specific prescriptions). After a year of chatbot design and development, the test version obtained good evaluation scores: its speed was rated 8.2/10, usability 8.1/10, and appearance 7.5/10. Testers were generally satisfied (70%) and were hoping for the content to be enhanced. CONCLUSIONS The chatbot seems to be a relevant tool for hospital caregivers, helping them to get reliable and verified information they need on drugs and pharmacy organization. In the context of significant mobility of nursing staff during the health crisis due to COVID-19, the chatbot could be a suitable tool for transmitting relevant information related to drugs circuits or specific procedures. To our knowledge, this is the first time that such a tool has been designed for caregivers. Its development further continued by means of tests conducted with other users such as pharmacy technicians, and via the integration of additional data, before the implementation on the two hospital sites.

Carbene‐Type Amidoosmium Complexes with an OsN Double Bond: Synthesis, Structure and Reactivity of [(Mes)Os(=NHR)(PiPr₃)]PF₆*The reaction of [(Mes)Os(PiPr₃)Cl₂] (1) (Mes1,3,5‐C₆H₃Me₃) with primary amines RNH₂ (RPh, Me, Et) in acetone/water (1:1) gives, after addition of KPF₆, the amidoosmium(II) complexes [(Mes)Os(=NHR)(PiPr₃)]PF₆ (2–4) in 60–80% yield. From 1 and Et₂NH, the chloro(hydrido)compound [(Mes)1‐OsH(PiPr₃)Cl] (5) is formed. The X‐ray structural analysis of 2 reveals that the geometry around the osmium atom is trigonalplanar (with the midpoint of the mesitylene ring as one coordination site) and that the OsN distance of 1.923(4) Å is in agreement with an OsN double bond. Thermolysis of 4 (REt) at 165°C leads to the formation of the aldimino(hydrido)osmium complex [(Mes)OsH(NHCHMe)(PiPr₃)]PF₆ (6) by β1‐hydride migration from the NCH₂ carbon atom to the metal atom. Protonation of 3 (RMe) with HCl gives the amine complex [(Mes)Os(NH₂Me)(PiPr₃)Cl]PF₆ (7), whereas on treatment of 3 and 4 with CD₃NO₂ the deuterated derivatives [(Mes)Os(=NDR)(PiPr₃)]PF₆ ([D₁]‐3, [D₁]‐4) are almost quantitatively formed. Compound 2 (RPh) reacts with KOtBu by proton abstraction and phosphane elimination to give the dinuclear imidoosmium complex [(Mes)₂Os₂(μ1‐NPh)₂] (8).