Synthesis and automated fluorine-18 radiolabeling of new PSMA-617 derivatives with a CuAAC radiosynthetic approach

In the last decade, the development of new radiopharmaceuticals for the imaging and therapy of prostate cancer has been a highly active and important area of research, especially focusing on the prostate-specific membrane antigen (PSMA), an antigen which is upregulated in prostate, as well as in other tumor cells. A large variety of PSMA ligands have been radiolabeled, to date. Among the various derivatives, PSMA-617 resulted to be one of the most interesting in terms of interaction with the antigen and clinical properties, and its lutetium-177 labeled version has recently been approved by regulatory agencies for therapeutic purposes. For this reasons, the radiolabeling with fluorine-18 of a PSMA-617 derivative might be of interest. Beside other methodologies to radiolabel macromolecules with fluorine-18, the “click-chemistry” approach resulted to be very useful, and the copper-catalyzed azide-alkyne cycloaddition (CuAAC) is considered one of most efficient and reliable. This paper proposes the synthesis of a suitable precursor for the radiolabeling with fluorine-18 of a new PSMA-617 derivative. The whole radiosynthetic procedure has been fully automated, and the final product, which proved to be stable in plasma, has been obtained with radiochemical yield and purity suitable for subsequent preclinical studies.     

Real world outcomes with Bortezomib Thalidomide dexamethasone and Cyclophosphamide Bortezomib dexamethasone induction treatment for transplant eligible multiple myeloma patients in a Latin American country. A Retrospective Cohort Study from Grupo Argentino de Mieloma Múltiple

Data about treatment outcomes and toxicity in Latin America are scarce. There are differences with central countries based on access to healthcare system and socioeconomic status. Argentinean Society of Hematology recommends bortezomib-based triplets for induction treatment of transplant eligible newly diagnosed multiple myeloma patients. Most common options are CyBorD (cyclophosphamide, bortezomib and dexamethasone) and VTD (bortezomib, thalidomide and dexamethasone). Main goal of our retrospective, multicentric study was to compare very good partial response rate (VGPR) or better after induction treatment in a real-world setting in Argentina. Secondary objectives included comparison of complete response (CR) post-induction and after bone marrow transplantation, grade 3-4 adverse events (AEs), progression-free survival (PFS) and overall survival (OS). Three hundred twenty-two patients were included (median age at diagnosis: 57 years; 52% male; 28% had ISS3; 14% with high-risk cytogenetics; median follow up: 34 months). CyBorD was indicated in 74% and 26% received VTD. In VTD arm, 72.62% of patients achieved at least VGPR vs 53.36% receiving CyBorD (odds ratio, OR: 1.96 [95% confidence interval, CI: 1.08-3.57; P = .026] after adjusting by age, ISS [International Staging System], lactate dehydrogenase levels (LDH) and cytogenetic risk. Difference in VGPR was 19.26% (95% CI: 15-24). CR rate were 35.92% (VTD) vs 22.55% (CyBorD) (adjusted OR: 2.13 [95% CI: 1.12-4.05]). Difference in CR was 13.37% (95% CI: 9.6-17.53). Adverse events (AEs) were more common with VTD (69.05% vs 55.46% for CyBorD; P = .030), especially grade 3-4 neuropathy (P = .005) and thrombosis (P = .001). Thromboprophylaxis was inadequate in 20.24% of patients. Hematological AEs were more common with CyBorD, especially thrombocytopenia (P = .017). PFS and OS at 24 months were not different between treatments. In this real-world setting, VTD was associated with better CR and VGPR than CyBorD. Nevertheless, CyBorD continues to be the preferred induction regimen in Argentina, based on safety profile. Frontline autologous stem cell transplantation improves quality of responses, especially in countries with limited access to new drugs.     

Idoneit al lavoro in operatore dei corpi di polizia in trattamento per OSAS

Fitness for working in a policeman being treated for OSAS. A policeman who has been ill with OSAS for 10 years is in optimal CPAP therapy. During this time, the overall assessment of his work activities was excellent and he had no traffic accidents or accidents at work. Concerning his work as a policeman, the Medical Commission of 1st instance considered him unfit to work. Conversely, the Medical Commission of 2nd instance declared him fit to work. In the adult general population, the prevalence of moderate and severe OSAS is more than 20%. It is therefore likely that there are many policemen affected by OSAS and the number of requests for assessments of fitness to work in those with OSAS will increase. It is a priority: (i) to integrate the training course of the medical staff of the Police Forces and the Armed Forces with updates on OSAS; (ii) to delete OSAS from the list of chronic diseases for which night shift work is not indicated.Key words: Obstructive sleep apnea syndrome, fitness for work, public health     

Mechanochemical Endovenous Ablation of Varicose Veins in Pediatric Patients with Klippel-Trénaunay Syndrome: Feasibility,Safety, and Initial Results

PurposeTo evaluate feasibility, safety, and results of endovenous mechanochemical ablation (MOCA) for treatment of persistent embryonic and dysplastic veins in pediatric patients with Klippel-Trénaunay syndrome (KTS).Materials and MethodsThirteen MOCA procedures were performed in 11 patients (age range, 4–16 years) with KTS and symptomatic persistent embryonic or dysplastic veins during a 24-month period. All patients were evaluated with color Doppler (CD) ultrasound (US), contrast-enhanced MR imaging, and venography to assess the anatomy of the target vessels and patency of the deep venous system. All procedures were performed under general anesthesia with a ClariVein catheter and liquid sodium tetradecyl sulfate as the sclerosing agent. US and fluoroscopic guidance were used in all cases. Technical success rate, primary occlusion rate, adverse effects, and recanalization rates were evaluated. Clinical and radiological (CD US) controls were performed 1 day, 7 days, 1 month, and 6 months after the procedure and once a year thereafter, with a mean follow-up of 16 months (range, 6–25 months).ResultsTechnical success and primary occlusion were achieved in all patients with no adverse events. During the follow-up period, CD US demonstrated partial recanalization and symptom recurrence in 2 patients (18%), 14 and 18 months after the initial procedure. These 2 patients had a second ablation procedure with no recanalization or symptom recurrence during the subsequent follow-up period.ConclusionsMOCA is feasible and appears to be a safe and effective technique for treatment of varicose veins in pediatric patients with KTS.     

Bail-out intracranial stenting with Solitaire AB device after unsuccessful thrombectomy in acute ischemic stroke of anterior circulation

Background

Recent trials established the efficacy of mechanical stent-retriever thrombectomy for treatment of stroke patients with large vessel occlusion (LVO) in the anterior circulation. However, stent-retriever thrombectomy may not accomplish successful recanalization in all patients. The aim of this study is to report the role of bail-out permanent stenting after failure of mechanical thrombectomy.

Deformación miocárdica de la aurícula izquierda en pacientes con lupus eritematoso sistémico

BackgroundIn patients with systemic lupus erythematosus (SLE), left ventricle diastolic dysfunction (LVDD) may be the only manifestation of cardiac involvement in anticipation of systolic dysfunction. It has been seen that myocardial deformation of the left atrium (LA), through the LA global longitudinal strain (LAGLS), may be useful in assessing diastolic function.ObjectiveTo evaluate LA function through myocardial deformation in patients with LES, and compare the LA strain in patients with active, inactive and controls.MethodsFifty patients with SLE were included and compared with 50 healthy controls paired by age and gender. Myocardial deformation was measured by transthoracic echocardiogram, to investigate the LAGLS, the strain of the three phases of the LA cycle and the strain rate. The differences between groups were compared in univariate analysis.ResultsLAGLS in SLE patients was less than in the controls (41.6% vs. 50.5%; p = .02), and in the 3 phases of the LA cycle. There were no differences in the LA strain rate in both groups (SLE 2.5 s^?1 vs. controls 2.75 s^?1; p = .1). It was also found that the LAGLS was lesser in active patients than controls and inactive.ConclusionsSLE patients have lower myocardial deformation of the LA, which is expressed as a lower diastolic function correlating with early subclinical myocardial damage.