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.     

The magnitude and progress of lean body mass,fat-free mass,and skeletal muscle mass loss following bariatric surgery: A systematic review and meta-analysis

Postbariatric loss of muscle tissue could negatively affect long-term health due to its role in various bodily processes, such as metabolism and functional capacity. This meta-analysis aimed to unravel time-dependent changes in the magnitude and progress of lean body mass (LBM), fat-free mass (FFM), and skeletal muscle mass (SMM) loss following bariatric surgery. A systematic literature search was conducted in Pubmed, Embase, and Web of Science. Fifty-nine studies assessed LBM (n = 37), FFM (n = 20), or SMM (n = 3) preoperatively and ≥1 time points postsurgery. Random-effects meta-analyses were performed to determine pooled loss per outcome parameter and follow-up time point. At 12-month postsurgery, pooled LBM loss was ?8.13 kg [95%CI ?9.01; ?7.26]. FFM loss and SMM loss were ?8.23 kg [95%CI ?10.74; ?5.73] and ?3.18 kg [95%CI ?5.64; ?0.71], respectively. About 55% of 12-month LBM loss occurred within 3-month postsurgery, followed by a more gradual decrease up to 12 months. Similar patterns were seen for FFM and SMM. In conclusion, >8 kg of LBM and FFM loss was observed within 1-year postsurgery. LBM, FFM, and SMM were predominantly lost within 3-month postsurgery, highlighting that interventions to mitigate such losses should be implemented perioperatively.     

Exploring the role of artificial intelligence in the study of fetal heart

The International Journal of Cardiovascular Imaging -     

The role of endoscopic ultrasound for portal hypertension in liver cirrhosis

Journal of Medical Ultrasonics - Chronic liver disease is still a major problem because disease progression will ultimately lead to liver cirrhosis. Portal hypertension is the hallmark in advanced...     

Glycaemic control for patients with severe acute brain injury: Protocol for a systematic review

Background

Hyperglycaemia is common in patients with acute brain injury admitted to an intensive care unit (ICU). Many studies have found associations between development of hyperglycaemia and increased mortality in hospitalised patients. However, the optimal target for blood glucose control is unknown. We want to conduct a systematic review with meta-analysis and trial sequential analysis to explore the beneficial and harmful effects of restrictive versus liberal glucose control on patient outcomes in adults with severe acute brain injury.

Methods

We will systematically search medical databases including CENTRAL, Embase, MEDLINE and trial registries. We will search the following websites for ongoing or unpublished trials: http://www.controlled-trials.com/ , http://www.clinicaltrials.gov/ , www.eudraCT.com , http://centerwatch.com/ , The Cochrane Library's CENTRAL, PubMed, EMBASE, Science Citation Index Expanded and CINAHL. Two authors will independently review and select trials and extract data. We will include randomised trials comparing levels of glucose control in our analyses and observational studies will be included to address potential harms. The primary outcomes are defined as all-cause mortality, functional outcome and health-related quality of life. Secondary outcomes include serious adverse events including hypoglycaemia, length of ICU stay and duration of mechanical ventilation, and explorative outcomes including intracranial pressure and infection. Trial Sequential Analysis will be used to investigate the risk of type I error due to repetitive testing and to further explore imprecision. Quality of trials will be evaluated using the Cochrane Risk of Bias tool, and quality of evidence will be assessed using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach.

Discussion

The results of the systematic review will be disseminated through peer-reviewed publication. With the review, we hope to inform future randomised clinical trials and improve clinical practice.     

COVID-19 pandemic,as experienced in the surgical service of a district hospital in Spain

The coronavirus disease 2019, which is caused by severe acute respiratory syndrome coronavirus 2, was first identified in December 2019 in Wuhan, China, and has since spread rapidly, evolving into a full-blown pandemic. We would like to report our experience after 1 year of this pandemic in the surgical service of a district hospital in Spain. There have been many changes (including new protocols) that our service and the hospital have undergone, to adapt to the new situation. We believe that this experience can be useful for other professionals who have lived and are living a similar situation.     

Comparison of the treatment results of knee osteoarthritis using adipose tissue mesenchymal stromal cells derived through enzymatic digestion and mechanically fragmented adipose tissue

Introduction:Knee osteoarthritis is a common condition that affects daily functioning and decreases the quality of life. There are many ways of treatment depending on the stage of the disease. Advanced cases are qualified for arthroplasty, which is an extensive and demanding surgical procedure. Less advanced stages are treated in various ways: from rehabilitation, through oral and intra-articular pharmacotherapy, to surgical treatment (arthroscopy, osteotomy). Because surgical treatment is risky, scientists focus on less invasive therapeutic methods. The most valuable management is based on regeneration. Mesenchymal stromal cells (MSC) derived from the adipose tissue have a great regenerative and anti-inflammatory potential, therefore an attempt is being made to take advantage of them in knee osteoarthritis treatment.The study aims to compare the clinical effects of treatment of knee osteoarthritis using adipose tissue MSC obtained by an enzymatic method with the outcomes of the therapy with the mechanically fragmented adipose tissue.Methods:One hundred adults with primary knee osteoarthritis will undergo lipoaspiration under sterile conditions. The collected lipoaspirates will be further processed, depending on the randomly assigned group-enzymatically with the use of collagenase or mechanically using the Lipogems system. The preparations will be administered to the patients’ knee joints in the operating room under ultrasound control.The results of treatment will be assessed using Knee Injury and Osteoarthritis Outcome Score, measuring the flexibility of the knee joint, evaluating joint gap in X-ray and the quality of cartilage in magnetic resonance T2-mapping during 1 year after treatment.Discussion/conclusion:Identification and functional analysis of the regenerative capacity of adipose-derived MSC depending on three variables (body weight, sex, and age) will help to develop a targeted therapy for different groups of patients and will determine the effectiveness of both methods of treatment. An attempt will be made to identify groups of patients with the greatest regenerative potential of the adipose tissue, and thus indicate those with the most probable improvement of the joint condition.Trial registration:This study protocol has been approved by the Ethics Committee of Medical University of Warsaw and registered on www.clinicaltrials.gov: {"type":"clinical-trial","attrs":{"text":"NCT04675359","term_id":"NCT04675359"}}NCT04675359 (06 Jan 2021)