ABSTRACT
Patients with non-alcoholic fatty liver disease (NAFLD) have an increased risk of developing progressive fibrosis, cirrhosis, and hepatocellular carcinoma. As of now, there are no FDA-approved treatments for NAFLD/non-alcoholic steatohepatitis (NASH) or its associated fibrosis. Although many drugs are under clinical trial, both obeticholic acid (OCA) and semaglutide are among the few that have reached phase III clinical trials, but they were never compared. We decided to conduct a systematic review of randomized controlled trials and meta-analyses. A total of 6,589 articles were found after searching PubMed, OVID Embase, OVID Medline, PubMed Central, and clinicaltrials.gov. Only full-text peer-reviewed articles published in the past six years were put through the Cochrane bias assessment tool or the Assessment of Multiple Systematic Reviews (AMSTAR) tool to screen for bias. After strict quality assessment, data from five randomized controlled trials (n=2,694) and three systematic reviews/meta-analysis (n=8,898) was extracted and included. The data extraction from these studies showed that semaglutide and OCA cause histological improvement, but NASH resolution is exclusive to semaglutide. Although high doses of OCA can cause dyslipidemia and severe pruritus, it is the only therapeutic that causes improvement in NASH-associated hepatic fibrosis. Semaglutide is the safest option among the two and leads to significant weight loss compared to OCA; thus, a better outcome on hepatic steatosis follows. The indications of each of these drugs should be based on the NAFLD activity score and NASH fibrosis stage. OCA should be used with caution among patients with hyperlipidemia and ischemic heart disease as it may make these conditions worst.
ABSTRACT
Sickle cell disease (SCD) is a group of inherited red blood cell disorders affecting millions worldwide. The median life expectancy of someone with SCD remains significantly low despite improvements in standards of care and the implementation of hydroxyurea therapy. Notably, a 20-year interval existed (after the implementation of hydroxyurea therapy) prior to the approval of other sickle cell medications, namely, l-glutamine, voxelotor, and crizanlizumab. In this systematic review, these new medications' impact on the occurrences of vaso-occlusive crisis (VOC) events were analyzed and the adverse events of each were noted. Further, a secondary analysis was conducted to determine the effect of combination therapies, whether synergistic, antagonistic, or additive. The systematic review was conducted following the PRISMA 2020 guidelines. The effect-based and dose-effect-based approaches were utilized to determine the combined drugs combination index based on the recommended dosage to achieve an efficacy of 50%. L-glutamine and crizanlizumab were effective in reducing the frequency of VOC (p= 0.0216 and p = 0.02). Voxelotor effect on the reduction of VOC occurrences was not significant, however, its effect on increasing hemoglobin levels was significant (p= <0.001). In all three therapies, pain was the most common adverse event reported by participants. The analysis of combination therapies revealed that voxelotor plus l-glutamine was synergistic, voxelotor plus crizanlizumab was antagonistic, and l-glutamine plus crizanlizumab was additive. Thus, voxelotor plus l-glutamine combination therapy may be more beneficial to sickle cell disease patients. As such, robust combination drug studies for approved therapies used in SCD should be initiated with a specific focus on voxelotor plus l-glutamine. Additionally, the development of medications that lessen the pain burden in sickle cell disease patients should also be prioritized.
ABSTRACT
Moyamoya disease is defined as stenosis of the internal carotid artery or the middle, anterior or posterior cerebral arteries with considerable collateral development. This collateral vessel has a particular appearance in angiographic examinations. Moyamoya syndrome is a term used to describe when moyamoya disease occurs in conjunction with other systemic disorders. One of the associations is Down syndrome. Moyamoya syndrome is very common in patients with Down syndrome, and the cause for this is unknown. The majority of patients present in their first decade, with the clinical presentation varying with age. The cause of moyamoya syndrome in people with trisomy 21 is unknown. This research aimed to learn more about the genesis and pathology of moyamoya syndrome in people with Down syndrome. The Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines were used to conduct this systematic review. Several publications connected to this topic were searched through a comprehensive database search. They were narrowed down to a final number of ten articles after applying inclusion and exclusion criteria and analyzing the quality of each work. Several possibilities were presented in these final papers to explain the link between moyamoya syndrome and trisomy 21. Trisomy 21 patients have a genetic predisposition to vascular problems. The RNF213 gene may interact with the genes on chromosome 21 that influence vascular physiology and elasticity in patients with Down syndrome, resulting in the whole picture of moyamoya syndrome.
