Synthesis and SAR evaluation of coumarin derivatives as potent cannabinoid receptor agonists

We report the development and extensive structure-activity relationship evaluation of a series of modified coumarins as cannabinoid receptor ligands. In radioligand, and [S-35]GTP gamma S binding assays the CB receptor binding affinities and efficacies of the new ligands were determined. Furthermore, we used a ligand-based docking approach to validate the empirical observed results. In conclusion, several crucial structural requirements were identified. The most potent coumarins like 3-butyl-7-(1-butylcyclopentyl)-5-hydroxy-2H-chromen-2-one (36b, K-i CB2 13.7 nM, EC50 18 nM), 7-(1-butylcyclohexyl)-5-hydroxy-3-propyl-2H-chromen-2-one (39b, K-i CB2 6.5 nM, EC50 4.51 nM) showed a CB2 selective agonistic profile with low nanomolar affinities. (C) 2021 Published by Elsevier Masson SAS.Peer reviewe

Prognosis of shoulder pain in those with and without a psychological disorder:A prospective cohort study with a six-month follow-up

BACKGROUND: Because shoulder pain can have an unfavorable prognosis, it is important to have a better understanding of factors that may influence recovery. OBJECTIVE: To determine the association between recovery from shoulder pain and the presence of depression, anxiety, and pain catastrophizing. METHODS: In a prospective cohort study with a six months follow-up, we included patients visiting an orthopaedic department with shoulder pain. Primary outcome was recovery from shoulder pain measured with the Shoulder Pain and Disability Index at three and six months. Information about depression and anxiety (Hospital Anxiety and Depression Scale), pain catastrophizing (Pain Catastrophizing Scale), and demographic and clinical factors were collected at baseline. A linear mixed model was used to estimate the effects of depression, anxiety, pain catastrophizing, and underlying shoulder disorders on recovery. RESULTS: We included 190 patients. There were no statistically significant associations between the presence of depression, anxiety, and pain catastrophizing, and three- and six-month recovery. Also between the underlying shoulder disorders and recovery at three and six months, there were no statistically significant associations. CONCLUSIONS: We could not prove that depression, anxiety, and pain catastrophizing, as well as underlying shoulder disorders, were associated with recovery of shoulder pain at six months

Multicenter Observational Study of Adhesion Formation After Open-and Laparoscopic Surgery for Colorectal Cancer

Objective: The aim of this study was to compare adhesion formation after laparoscopic and open colorectal cancer resection. Summary of Background Data: After colorectal surgery, most patients develop adhesions, with a high burden of complications. Laparoscopy seems to reduce adhesion formation, but evidence is poor. Trials comparing open- and laparoscopic colorectal surgery have never assessed adhesion formation. Methods: Data on adhesions were gathered during resection of colorectal liver metastases. Incidence of adhesions adjacent to the original incision was compared between patients with previous laparoscopic- and open colorectal resection. Secondary outcomes were incidence of any adhesions, extent and severity of adhesions, and morbidity related to adhesions or adhesiolysis. Results: Between March 2013 and December 2015, 151 patients were included. Ninety patients (59.6%) underwent open colorectal resection and 61 patients (40.4%) received laparoscopic colorectal resection. Adhesions to the incision were present in 78.9% after open and 37.7% after laparoscopic resection (P < 0.001). The incidence of abdominal wall adhesions and of any adhesion was significantly higher after open resection; the incidence of visceral adhesions did not significantly differ. The extent of abdominal wall and visceral adhesions and the median highest Zühlke score at the incision were significantly higher after open resection. There were no differences in incidence of small bowel obstruction during the interval between the colorectal and liver operations, the incidence of serious adverse events, and length of stay after liver surgery. Conclusion: Laparoscopic colorectal cancer resection is associated with a lower incidence, extent, and severity of adhesions to parietal surfaces. Laparoscopy does not reduce the incidence of visceral adhesions

Variation in the management of benign liver tumors: A European survey and case vignette study

Background: Management of focal nodular hyperplasia (FNH) and hepatocellular adenoma (HCA), is multidisciplinary and subject to practice variation. We aimed to evaluate variation in clinical management of FNH and HCA in Europe. Methods: We distributed an online survey (November 2021–March 2022) among 294 European experts. The survey included questions on local practice and included eight clinical vignettes. The clinical vignettes focused on FNH or HCA management in the setting of sex, lifestyle modification, and pregnancy. Results: The response rate was 32% and respondents included surgeons (38%), gastroenterologists/hepatologists (25%), radiologists (32%), and pathologists (1.6%) from ten European countries. We observed practice variation with regard to lifestyle modification and imaging follow-up in patients with FNH, and with regard to the management of HCA >5 cm before and during pregnancy. Finally, the management of HCA >5 cm after lifestyle modification deviated from EASL guideline recommendations. Conclusion: Our survey illustrates variability in FNH and HCA management in Europe. Several areas were identified for future research and guideline recommendations, including FNH follow-up and the management of HCA >5 cm. We propose the organization of Delphi consensus meetings to prioritize areas of research and update current guidelines to optimize management for all patients with benign liver tumors