Treatment of Later Humoral Rejection with Anti-CD20 Monoclonal Antibody Rituximab: A Single Centre Experience

Humoral or vascular rejection is a B cell-mediated production of immunoglobulin (Ig) G antibody against a transplanted organ that results in immune complex deposition on the vascular endothelium, activation of the complement cascade, production of endothelial dysfunction and regional ischaemic injury

[¹⁸F]fluorination of biorelevant arylboronic acid pinacol ester scaffolds synthesized by convergence techniques

Aim: The development of small molecules through convergent multicomponent reactions (MCR) has been boosted during the last decade due to the ability to synthesize, virtually without any side-products, numerous small drug-like molecules with several degrees of structural diversity.(1) The association of positron emission tomography (PET) labeling techniques in line with the “one-pot” development of biologically active compounds has the potential to become relevant not only for the evaluation and characterization of those MCR products through molecular imaging, but also to increase the library of radiotracers available. Therefore, since the [18F]fluorination of arylboronic acid pinacol ester derivatives tolerates electron-poor and electro-rich arenes and various functional groups,(2) the main goal of this research work was to achieve the 18F-radiolabeling of several different molecules synthesized through MCR. Materials and Methods: [18F]Fluorination of boronic acid pinacol esters was first extensively optimized using a benzaldehyde derivative in relation to the ideal amount of Cu(II) catalyst and precursor to be used, as well as the reaction solvent. Radiochemical conversion (RCC) yields were assessed by TLC-SG. The optimized radiolabeling conditions were subsequently applied to several structurally different MCR scaffolds comprising biologically relevant pharmacophores (e.g. β-lactam, morpholine, tetrazole, oxazole) that were synthesized to specifically contain a boronic acid pinacol ester group. Results: Radiolabeling with fluorine-18 was achieved with volumes (800 μl) and activities (≤ 2 GBq) compatible with most radiochemistry techniques and modules. In summary, an increase in the quantities of precursor or Cu(II) catalyst lead to higher conversion yields. An optimal amount of precursor (0.06 mmol) and Cu(OTf)2(py)4 (0.04 mmol) was defined for further reactions, with DMA being a preferential solvent over DMF. RCC yields from 15% to 76%, depending on the scaffold, were reproducibly achieved. Interestingly, it was noticed that the structure of the scaffolds, beyond the arylboronic acid, exerts some influence in the final RCC, with electron-withdrawing groups in the para position apparently enhancing the radiolabeling yield. Conclusion: The developed method with high RCC and reproducibility has the potential to be applied in line with MCR and also has a possibility to be incorporated in a later stage of this convergent “one-pot” synthesis strategy. Further studies are currently ongoing to apply this radiolabeling concept to fluorine-containing approved drugs whose boronic acid pinacol ester precursors can be synthesized through MCR (e.g. atorvastatin)

A Systematic Review and Meta-Analysis of the Incidence of Injury in Professional Female Soccer

The epidemiology of injury in male professional football is well documented and has been used as a basis to monitor injury trends and implement injury prevention strategies. There are no systematic reviews that have investigated injury incidence in women’s professional football. Therefore, the extent of injury burden in women’s professional football remains unknown. PURPOSE: The primary aim of this study was to calculate an overall incidence rate of injury in senior female professional soccer. The secondary aims were to provide an incidence rate for training and match play. METHODS: PubMed, Discover, EBSCO, Embase and ScienceDirect electronic databases were searched from inception to September 2018. Two reviewers independently assessed study quality using the Strengthening the Reporting of Observational Studies in Epidemiology statement using a 22-item STROBE checklist. Seven prospective studies (n=1137 professional players) were combined in a pooled analysis of injury incidence using a mixed effects model. Heterogeneity was evaluated using the Cochrane Q statistic and I2. RESULTS: The epidemiological incidence proportion over one season was 0.62 (95% CI 0.59 - 0.64). Mean total incidence of injury was 3.15 (95% CI 1.54 - 4.75) injuries per 1000 hours. The mean incidence of injury during match play was 10.72 (95% CI 9.11 - 12.33) and during training was 2.21 (95% CI 0.96 - 3.45). Data analysis found a significant level of heterogeneity (total Incidence, X2 = 16.57 P < 0.05; I2 = 63.8%) and during subsequent sub group analyses in those studies reviewed (match incidence, X2 = 76.4 (d.f. = 7), P <0.05; I2 = 90.8%, training incidence, X2 = 16.97 (d.f. = 7), P < 0.05; I2 = 58.8%). Appraisal of the study methodologies revealed inconsistency in the use of injury terminology, data collection procedures and calculation of exposure by researchers. Such inconsistencies likely contribute to the large variance in the incidence and prevalence of injury reported. CONCLUSIONS: The estimated risk of sustaining at least one injury over one football season is 62%. Continued reporting of heterogeneous results in population samples limits meaningful comparison of studies. Standardising the criteria used to attribute injury and activity coupled with more accurate methods of calculating exposure will overcome such limitations