A contemporary systematic review on liver transplantation for unresectable liver metastases of colorectal cancer

The 5-year overall survival rate of a patient with unresectable metastatic colorectal cancer is poor at approximately 14%. Similarly, historical data on liver transplantation (LT) in those with colorectal liver metastases (CRLM) showed poor outcomes, with 5-year survival rates between 12% and 21%. More recently, limited data have shown improved outcomes in select patients with 5-year overall survival rates of approximately 60%. Despite these reported survival improvements, there is no significant improvement in disease-free survival. Given the uncertain benefit with this therapeutic approach and a renewed investigational interest, we aimed to conduct a contemporary systematic review on LT for CRLM. A systematic review of the literature was performed according to the preferred reporting items for systematic reviews and meta-analysis statement. English articles reporting on data regarding LT for CRLM were identified through the MEDLINE (via PubMed), Cochrane Library, and ClinicalTrials.gov databases (last search date: December 16th, 2021) by 2 researchers independently. A total of 58 studies (45 published and 13 ongoing) were included. Although early retrospective studies suggest the possibility that some carefully selected patients may benefit from LT, there is minimal prospective data on the topic and LT remains exploratory in the setting of CRLM. Additionally, several other challenges, such as the limited availability of deceased donor organs and defining appropriate selection criteria, remain when considering the implementation of LT for these patients. Further evidence from ongoing prospective trials is needed to determine if and to what extent there is a role for LT in patients with surgically unresectable CRLM.     

Serum uric acid in patients with ST-segment elevation myocardial infarction: An innocent bystander or leading actor?

Elevated serum uric acid (SUA) levels have been associated with several cardiovascular risk factors and the progression of coronary artery disease. In the setting of acute myocardial infarction, increasing evidence suggests that high SUA levels could be related to adverse outcomes. Interestingly elevated SUA levels have been linked to endothelial dysfunction, inflammation and oxidative stress. The aim of this review is to discuss the potential negative effects of SUA in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention, analyzing the possible underlying pathophysiological mechanisms.     

Efficacy and Safety of Transjugular Intrahepatic Portosystemic Shunt Creation for Budd-Chiari Syndrome: A Systematic Review and Meta-Analysis

PurposeTo assess the critical role of transjugular intrahepatic portosystemic shunt (TIPS) in the management of Budd-Chiari syndrome (BCS), as the data with respect to the safety and outcome of TIPS in patients with BCS are scarce because of the rarity of the disease.Materials and MethodsA comprehensive search of literature of various databases from 2000 to October 2021 was conducted for studies evaluating the outcome of TIPS in patients with BCS. The primary outcomes of the analysis were technical and clinical success, adverse events and mortality associated with TIPS, dysfunction of TIPS, need for TIPS revision, need for liver transplantation (LT), and 1-year survival.ResultsA total of 33 studies (1,395 patients) were included in this meta-analysis. The pooled rates and 95% confidence intervals of various outcomes were 98.6% (97.6–99.7) for technical success, 90.3% (86.0–94.6) for clinical success, 10.0% (6.5–13.6) for major adverse events, 0.5% (0.2–1.0) for TIPS-related mortality, 11.6% (7.8–15.4) for post-TIPS hepatic encephalopathy (HE), 40.1% (32.5–47.7) for TIPS dysfunction, 8.6% (4.9–12.4) for the need for TIPS revision, 4.5% (2.8–6.2) for the need for LT, and 94.6% (93.1–96.1) for 1-year survival. Publication bias was seen with all outcomes except for post-TIPS HE, TIPS dysfunction, and the need for LT.ConclusionsThe existing literature supports the feasibility, safety, and efficacy of TIPS in the treatment of BCS. Deciding the optimal timing of TIPS in BCS needs further studies.     

Mechanism of action of Orthosiphon stamineus against non-alcoholic fatty liver disease: Insights from systems pharmacology and molecular docking approaches

Non-alcoholic fatty liver disease (NAFLD) is one of the most common complications of a metabolic syndrome caused by excessive accumulation of fat in the liver. Orthosiphon stamineus also known as Orthosiphon aristatus is a medicinal plant with possible potential beneficial effects on various metabolic disorders. This study aims to investigate the in vitro inhibitory effects of O. stamineus on hepatic fat accumulation and to further use the computational systems pharmacology approach to identify the pharmacokinetic properties of the bioactive compounds of O. stamineus and to predict their molecular mechanisms against NAFLD. Methods: The effects of an ethanolic extract of O. stamineus leaves on cytotoxicity, fat accumulation and antioxidant activity were assessed using HepG2 cells. The bioactive compounds of O. stamineus were identified using LC/MS and two bioinformatics databases, namely the Traditional Chinese Medicine Integrated Database (TCMID) and the Bioinformatics Analysis Tool for the Molecular Mechanism of Traditional Chinese Medicine (BATMAN-TCM). Pathway enrichment analysis was performed on the predicted targets of the bioactive compounds to provide a systematic overview of the molecular mechanism of action, while molecular docking was used to validate the predicted targets. Results: A total of 27 bioactive compounds corresponding to 50 potential NAFLD-related targets were identified. O. stamineus exerts its anti-NAFLD effects by modulating a variety of cellular processes, including oxidative stress, mitochondrial β-oxidation, inflammatory signalling pathways, insulin signalling, and fatty acid homeostasis pathways. O. stamineus is significantly targeting many oxidative stress regulators, including JNK, mammalian target of rapamycin (mTOR), NFKB1, PPAR, and AKT1. Molecular docking analysis confirmed the expected high affinity for the potential targets, while the in vitro assay indicates the ability of O. stamineus to inhibit hepatic fat accumulation. Conclusion: Using the computational systems pharmacology approach, the potentially beneficial effect of O. stamineus in NAFLD was indicated through the combination of multiple compounds, multiple targets, and multicellular components.     

The association between sport-related concussion and musculoskeletal injury in university rugby athletes

ObjectivesThe study aimed to analyse the association between Sports-Related Concussion (SRC) and Subsequent Musculoskeletal Injury (MSK) in United Kingdom university-aged rugby union players whilst considering the effects of sex, athlete playing position and injury location.DesignRetrospective cohort study. A period of 365 days with 0–90, 91–180 and 181–365 days sub-periods was analysed for the following variables; MSK injury incidence, occurrence, severity, injury location, playing position and sex.SettingInjury data was collected from the Sports Development Centre database at Loughborough University.ParticipantsA total of 408 injuries in 181 athletes (55 females and 126 males) were included.ResultsThe MSK injury incidence of SRC group was significantly higher than control and higher post-SRC than pre-SRC period over a 365-day period (p=0.012 and p=0.034, respectively). The odds ratios of MSK injury incidence between groups and between periods were 1.62 (95% CI, 1.10–2.25) and 1.57 (95% CI ,1.08–2.29). A SRC was not associated with a greater time loss from a subsequent MSK injury or a specific MSK injury location.ConclusionsAthletes with a second recorded injury were more likely to sustain a MSK injury if they had experienced SRC, however, there was no indication a SRC resulted in greater time loss from a MSK injury.