Reviews on Recent Clinical Trials - Volume 19, Issue 4, 2024

Bariatric surgery is one of the effective therapeutic options for people with obesity and obesity-related co-morbidities. In addition to weight-related co-morbid diseases, including diabetes, hypertension, and hypercholesterolemia, non-alcoholic fatty liver disease (NAFLD) is common in patients with morbid obesity. Bariatric surgery is one of the therapeutic options in the management of NAFLD. Hence, this review focused on the potential role of bariatric surgery on hepatic elasticity measured through shear wave elastography.

A systematic literature search was performed, and the studies regarding heterogeneity were evaluated using the random-effects model.

The meta-analysis on 6 trials (3-12 months follow-up) including 350 participants showed a significant reduction of liver elasticity after surgery (WMD: -1.149, 95% CI: -1.767, -0.532, p < 0.001; I2:81.55%).

Bariatric surgery is associated with decreased liver elasticity. This improvement could be related to weight loss or other mechanisms of bariatric surgery.

β-thalassemia imposes significant complications on affected patients. Silymarin, a natural flavonoid complex, has potential therapeutic properties.

This systematic review aims to comprehensively evaluate the literature on the mechanistic effects of Silymarin on β-thalassemia outcomes in children and adolescents.

A systematic search of electronic databases, including MEDLINE/PubMed, Embase, Scopus, Cochrane Library, and Web of Science (WOS), was done to identify relevant clinical trials before January 2024. Various data were extracted, including study characteristics, outcomes measured (hematological parameters, oxidative stress markers, iron metabolism, and other outcomes), proposed mechanisms, and safety.

By iron chelation effects, Silymarin can reduce reactive oxygen species (ROS) production, increase intracellular antioxidant enzyme glutathione (GSH), and insert antioxidant effects. It also attenuated inflammation through reduced tumor necrosis factor-alpha (TNF-α), transforming growth factor-β1 (TGF-β1), interferon-gamma (IFNγ), C-reactive protein (CRP), interleukin 6 (IL-6), IL-17, and IL-23 levels and increase in IL-4 and IL-10 levels. By reducing iron overload conditions, Silymarin indicates modulatory effects on immune abnormalities, inhibits red blood cell (RBC) hemolysis, increases RBC count, and minimizes the need for a transfusion. Moreover, it reduces myocardial and hepatic siderosis, improves liver function tests, and modifies abnormal enzymes, particularly for aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), total bilirubin, and total protein levels. Silymarin also reduces iron overload, increases antioxidant and anti-inflammatory capacity in cardiomyocytes, and reveals antioxidant effects.

Silymarin indicates promising effects on various aspects of children and adolescents with β-thalassemia and has no serious side effects on the investigated dosage.

Most of the mortality after Heart Transplantation (HT) is attributed to severe cardiac allograft vasculopathy (CAV) and rejection.

This meta-analysis aimed to investigate the effects of postoperative statin therapy on outcomes (mortality, rejection, and CAV in HT patients).

This systematic review and meta-analysis was performed on publications between 1980 and October 2023 in Web of Science, Scopus, PubMed, Cochrane, Science Direct, Google Scholar, and Embase databases. Heterogeneity was assessed using Chi-square, I², and forest plots. Publication bias was evaluated using Begg's and Egger's tests. Analyses were performed in Stata 15 with significance at p < 0.05.

This meta-analysis included 17 studies comprising 4,627 participants and conducted between 1995 to 2021. Compared to non-users, the odds of mortality were lower among statin users (OR= 0.49, 95% CI: 0.32–0.75, p < 0.001). The odds of CAV were also reduced with statin use (OR= 0.71, 95% CI: 0.53–0.96, p = 0.027). The odds of rejection were not significantly different (OR= 0.69, 95% CI: 0.41–1.15, p = 0.152). However, rejection odds were lower with statins in RCTs (OR= 0.42, 95% CI: 0.21–0.82, p = 0.012) but not in case-control studies (OR= 0.87, 95% CI: 0.49-1.52, p = 0.615). No publication bias was observed with Begg's test, but Egger's test showed possible bias.

This meta-analysis found postoperative statin use associated with lower mortality and CAV, but not overall rejection, though RCT subgroup analysis showed decreased rejection with statins. Statin therapy may improve prognosis in HT patients.

SARS-CoV-2 infection has been associated with the impairment of several organs, including the liver. In addition, cases of autoimmune hepatitis have been described in association with COVID-19 disease. According to some case reports, vaccination has also been suggested to elicit the immune liver disorder.

We report on the case series of two middle-aged women developing COVID-19 infection despite a completed vaccination schedule. More interestingly, the infection was followed by the onset of acute hepatitis with a significant increase in the values of liver function tests (x 10 normal values). After ruling out the main causes of liver damage (viral, toxic, etc.), a diagnosis of autoimmune hepatitis was made and supported by liver histology in both cases. The clinical picture was quickly reverted with immunosuppressive (steroid) therapy, also confirming the diagnosis.

We observed a possible relationship between COVID-19 infection and the onset of autoimmune hepatitis and also described this occurrence in vaccinated subjects. It remains to be clarified whether repeated exposure to viral antigens (vaccination plus true infection) or specific emerging viral genotype (omicron strain) may facilitate the onset of this immune liver disease.

Inflammatory Fibroid Polyp (IFP), also known as Vanek’s tumour, is a rare mesenchymal gastrointestinal tumour, potentially causing a wide range of clinical manifestations (even though it can be completely asymptomatic) primarily related to the location of the formation. The available evidence suggests a fundamentally non-neoplastic behaviour of IFP.

A 67-year-old female was presented with persistent dyspepsia despite symptomatic therapy. The patient's medical history included primary biliary cholangitis, managed with ursodeoxycholic acid, non-haemorrhagic uterine fibroids, and right knee arthrosis. Clinical examination revealed mild epigastric tenderness, and esophagogastroduodenoscopy identified a sessile mucosal formation. Histological analysis of biopsy samples revealed a gastric hyperplastic polyp, leading to a subsequent esophagogastroduodenoscopy for polypectomy. The excised specimen confirmed the diagnosis of gastric IFP. Post-polypectomy, the patient experienced progressive symptom amelioration, leading to complete resolution within three weeks.

This case thus describes a rare cause of dyspeptic syndrome associated with the presence of a gastric IFP, promptly managed and resolved after endoscopic removal of the polyp, with no histological signs of neoplasia within the en bloc resected sample.

IFP is a possible and rare cause of dyspeptic syndrome. There remain significant challenges in diagnosing this rare condition, which lacks pathognomonic or specific signs and symptoms of its presence (especially when it causes symptoms). Endoscopy, when feasible, remains a cornerstone in the resective management of such lesions.

This study aimed to assess the efficacy and safety of anti-VEGF combined with dexamethasone implant for the retinal vein occlusion patients with macular edema.

In this prospective, case-controlled, cohort clinical trial (Register ID: ChiCTR2400080048), patients with non-ischemic retinal vein occlusion were enrolled from the Sanmenxia Central Hospital from August 2020 to April 2023. The patients were randomized into two groups. All the patients received ranibizumab intravitreal injection in the first 3 consecutive months. For the ranibizumab group, anti-VEGF injections were as needed thereafter in case of recurrence of macular edema; For the combination group, the patients received an intravitreal dexamethasone implant injection at 15 days after the first ranibizumab injection. The primary outcome measurements were improvement in best corrected visual acuity (BCVA) and reduction in central macular thickness (CMT). The secondary outcomes were recurrence of macular edema, number of intravitreal injections, and injection interval. Safety profiles were also recorded.

A total of 124 patients were included, of which 73 patients completed all follow-ups. Both the ranibizumab monotherapy and the combination therapy significantly improved BCVA at all time points, compared to the baseline. The combined group achieved more BCVA improvement in 3 months, 6 months, and 12 months, compared to the ranibizumab alone group. Compared to the baseline, both groups achieved significant reductions in CMT at all follow-ups. However, the combination group showed more CMT reduction at 1 week post injection, compared to the ranibizumab group. The combination group had a significantly longer injection interval, lower injection time, and recurrence of macular edema. Ocular hypertension was the most common adverse events. Lastly, intraocular pressure was all well controlled by 1-3 glaucoma medications without surgical intervention.

The combination therapy could significantly improve the BCVA and reduce the CMT with a good safety profile.

ChiCTR2400080048.