Targeted Metabolomics Analysis of Individuals Carrying the ANGPTL8 R59W Variant.

ANGPTL8 is recognized as a regulator of lipid metabolism through its role in inhibiting lipoprotein lipase activity. ANGPTL8 gene variants, particularly rs2278426 leading to the R59W variant in the protein, have been associated with lipid traits in various ethnicities. We aimed to use metabolomics to understand the impact of the ANGPTL8 R59W variant on metabolites in humans. We used the Biocrates-p400 kit to quantify 408 plasma metabolites in 60 adult male Arab individuals from Kuwait and identify differences in metabolite levels between individuals carrying reference genotypes and those with carrier genotypes at ANGPTL8 rs2278426. Individuals with carrier genotypes (CT+TT) compared to those carrying the reference genotype (CC) showed statistically significant differences in the following metabolites: acylcarnitine (perturbs metabolic pathways), phosphatidylcholine (supports liver function and cholesterol levels), cholesteryl ester (brings chronic inflammatory response to lipoprotein depositions in arteries), α-aminoadipic acid (modulates glucose homeostasis), histamine (regulates glucose/lipid metabolism), sarcosine (links amino acid and lipid metabolism), diacylglycerol 42:1 (regulates homeostasis of cellular lipid stores), and lysophosphatidylcholine (regulates oxidative stress and inflammatory response). Functional aspects attributed to these metabolites indicate that the ANGPTL8 R59W variant influences the concentrations of lipid- and inflammation-related metabolites. This observation further highlights the role of ANGPTL8 in lipid metabolism.

Should Redo Surgery be Offered to Patients with Relapsed Glioblastoma? - Outcome Analyses of a Single Institution Comparative Cohort Study.

BACKGROUND: Glioblastoma multiforme (GBM) is the predominant malignant brain tumor originating intracranially. The established first-line treatment postsurgery is concurrent chemoradiation as a definitive measure. However, recurrent GBM's pose a challenge for clinicians who rely on institutional experience to determine the most suitable course of action. Second-line chemotherapy may be administered with or without surgery depending on the institution's practice. This study aims to present our tertiary center institution's experience with recurrent GBM patients who underwent redo surgery. METHODS: In this retrospective study we analyzed the surgical and oncological data of patients with recurrent GBM who underwent redo surgery at the Royal Stoke University Hospitals between 2006 and 2015. The group 1 (G1) comprised the reviewed patients, while a control group (G2) was randomly selected, matching the reviewed group by age, primary treatment, and progression-free survival (PFS). The study collected data on various parameters, including overall survival, PFS, extent of surgical resection, and postoperative complications. RESULTS: This retrospective study included 30 patients in G1 and 32 patients in G2, matched based on age, primary treatment, and PFS. The study found that the overall survival for the G1 group from the time of first diagnosis was 109 weeks (45-180) compared to 57 weeks (28-127) in the G2 group. The incidence of postoperative complications after the second surgery was 57%, which included hemorrhage, infarction, worsening neurology due to edema, cerebrospinal fluid leak, and wound infection. Furthermore, 50% of the patients in the G1 group who underwent redo surgery received second-line chemotherapy. CONCLUSIONS: Our study found that redo surgery for recurrent GBM is a viable treatment option for a select group of patients with good performance status, longer PFS from primary treatment, and compressive symptoms. However, the use of redo surgery varies depending on the institution. A well-designed randomized controlled trial in this population would help establish the standard of surgical care.

Targeted Metabolomics Analysis on Obstructive Sleep Apnea Patients after Multilevel Sleep Surgery.

BACKGROUND: Obstructive sleep apnea (OSA) is caused by partial or complete obstruction of the upper airways. Corrective surgeries aim at removing obstructions in the nasopharynx, oropharynx, and hypopharynx. OSA is associated with an increased risk of various metabolic diseases. Our objective was to evaluate the effect of surgery on the plasma metabolome. METHODS: This study included 39 OSA patients who underwent Multilevel Sleep Surgery (MLS). Clinical and anthropometric measures were taken at baseline and five months after surgery. RESULTS: The mean Apnea-Hypopnea Index (AHI) significantly dropped from 22.0 ± 18.5 events/hour to 8.97 ± 9.57 events/hour (p-Value < 0.001). Epworth's sleepiness Score (ESS) dropped from 12.8 ± 6.23 to 2.95 ± 2.40 (p-Value < 0.001), indicating the success of the surgery in treating OSA. Plasma levels of metabolites, phosphocholines (PC) PC.41.5, PC.42.3, ceremide (Cer) Cer.44.0, and triglyceride (TG) TG.53.6, TG.55.6 and TG.56.8 were decreased (p-Value < 0.05), whereas lysophosphatidylcholines (LPC) 20.0 and PC.39.3 were increased (p-Value < 0.05) after surgery. CONCLUSION: This study highlights the success of MLS in treating OSA. Treatment of OSA resulted in an improvement of the metabolic status that was characterized by decreased TG, PCs, and Cer metabolites after surgery, indicating that the success of the surgery positively impacted the metabolic status of these patients.