Background Cancer patients receiving chemotherapy have an increased risk of cardiovascular complications. This limits the widespread use of lifesaving therapies, often necessitating alternate lower efficacy regimens, or precluding chemotherapy entirely. Prior studies have suggested that using common cardioprotective agents may attenuate chemotherapy-induced cardiotoxicity. However, small sample sizes and conflicting outcomes have limited the clinical significance of these results. Hypothesis A comprehensive network meta-analysis using updated and high-quality data can provide more conclusive information to assess which drug or drug class has the most significant effect in the management of chemotherapy-induced cardiotoxicity. Methods We performed a literature search for randomized controlled trials (RCTs) investigating the effects of cardioprotective agents in patients with chemotherapy-induced cardiotoxicity. We used established analytical tools (netmeta package in RStudio) and data extraction formats to analyze the outcome data. To obviate systematic bias in the selection and interpretation of RCTs, we employed the validated Cochrane risk-of-bias tools. Agents included were statins, aldosterone receptor antagonists (MRAs), ACEIs, ARBs, and beta-blockers. Outcomes examined were improvement in clinical and laboratory parameters of cardiac function including a decreased reduction in left ventricular ejection fraction (LVEF), clinical HF, troponin-I, and B-natriuretic peptide levels. Results Our study included 33 RCTs including a total of 3,285 patients. Compared to control groups, spironolactone therapy was associated with the greatest LVEF improvement (Mean difference (MD) = 12.80, [7.90; 17.70]), followed by enalapril (MD = 7.62, [5.31; 9.94]), nebivolol (MD = 7.30, [2.39; 12.21]), and statins (MD = 6.72, [3.58; 9.85]). Spironolactone was also associated with a significant reduction in troponin elevation (MD = − 0.01, [− 0.02; − 0.01]). Enalapril demonstrated the greatest BNP reduction (MD = − 49.00, [− 68.89; − 29.11]), which was followed by spironolactone (MD = − 16.00, [− 23.9; − 8.10]). Additionally, patients on enalapril had the lowest risk of developing clinical HF compared to the control population (RR = 0.05, [0.00; 0.75]). Conclusion Our analysis reaffirmed that statins, MRAs, ACEIs, and beta-blockers can significantly attenuate chemotherapy-induced cardiotoxicity, while ARBs showed no significant effects. Spironolactone showed the most robust improvement of LVEF, which best supports its use among this population. Our analysis warrants future clinical studies examining the cardioprotective effects of cardiac remodeling therapy in cancer patients treated with chemotherapeutic agents.
The normal function of mitochondria in the hepatic parenchyma can be disrupted by ischemia/reperfusion (I/R) damage during liver transplantation. The pathology of these insults involves various cellular and molecular steps of events that have been extensively researched over decades but are yet to provide complete answers. This review discusses the brief mechanism of the pathophysiology following ischemia/reperfusion injury (IRI) and various targeting strategies that could result in improved graft function.The traditional treatment for end-stage liver disease i.e., liver transplantation, has been complicated by I/R damage. The poor graft function or primary non-function found after liver transplantation may be due to mitochondrial dysfunction following IRI. As a result, determining the sequence of incidents that cause human hepatic mitochondrial dysfunction is crucial; it might contribute to further improvements in the outcome of liver transplantation. Early discovery of novel prognostic factors involved in IRI could serve as a primary endpoint for predicting the outcome of liver grafts as well as promoting the early implementation of novel IRI-prevention strategies. In this review, recent developments in the study of mitochondrial dysfunction and I/R damage are discussed, specifically those concerning liver transplantation. Furthermore, we also explore different pharmacological therapeutic methods that may be used and their connections to mitochondrion-related processes and goals.Although significant progress has been made in our understanding of IRI and mitochondrial dysfunction, further research is needed to elucidate the cellular and molecular pathways underlying these processes to help identify biomarkers that can aid donor organ evaluation.
Anemia is a common complication of cancer. Treatment of anemia in cancer is crucial as anemia adversely affects the quality of life, therapeutic outcomes, and overall survival. Erythropoiesis stimulating agents (ESAs) are valuable drugs for treating cancer-related anemia. Cardiovascular adverse effects are a significant concern with ESA therapy, and there is wide variability in therapeutic goals and characteristics of patients who undergo treatment with ESAs. As a result, a careful analysis of the currently available data on the efficacy and safety of these drugs is necessary. This data analysis will aid in the rational use of ESAs for the treatment of anemia in cancer. The objective of this systematic review is to elucidate the pathogenesis of anemia in cancer, assess the effectiveness of ESAs in treating anemia in cancer, and the overall risk of cardiovascular adverse effects associated with the use of ESAs and their impact on prognosis. We searched literature from online databases - PubMed, PubMed Central, MEDLINE, Cochrane Library, and clinical trials register ( clinicaltrials.gov ) to identify prospective phase II and phase III randomized controlled trials (RCTs). We chose RCTs that directly compared patients with cancer who were treated with ESAs to those who were not treated with ESAs. January 2008 was taken as the lower date limit and May 2021 as the upper date limit. Only English language literature and human studies were included. The quality appraisal was completed using the Cochrane risk bias assessment tool, and data from a total of 10,738 patients with cancer in 17 RCTs were identified and included for systematic review. Our review concludes that ESAs effectively reduce the necessity for blood transfusions and increase mean hemoglobin levels in anemic cancer patients. ESA therapy is associated with cardiovascular adverse effects, including venous thromboembolism, thrombophlebitis, hypertension, ischemic heart disease, cardiac failure, arrhythmia, arterial thromboembolism, and cardiac arrest. Aggressive ESA dosing to achieve higher hemoglobin levels and preexisting uncontrolled hypertension increases these cardiovascular side effects. Venous thromboembolism is the most significant adverse effect attributed to ESA therapy. However, there is no major change in overall survival with ESA therapy, and administration of ESAs can be carried out in anemic cancer patients with careful assessment of thromboembolism risk factors, risk-benefit ratio, and monitoring of hemoglobin levels.
Traumatic brain injury of any severity can result in post-concussion syndrome (PCS). Although the postconcussive symptoms are complex, there is an emerging scientific consensus regarding the initiation of the treatment for these symptoms to improve quality of life and prevent long-term effects. The objective of this systematic review is to assess the comprehensive interventions used for the PCS and it aims to appraise if these interventions could prevent the development of depression as a complication. This research has used randomized controlled trials (RCTs) that evaluate the treatment of PCS and its effect on long-term complications like depression. We searched PubMed/MEDLINE, PubMed Central, Cochrane Central Register of Controlled Trials (CENTRAL), and EMBASE from January 1, 2016 to May 31, 2021 for our literature search. A quality check was conducted on the identified studies using the Cochrane risk of bias quality assessment tool (modified Cochrane RoB 2). In total, we included 11 RCTs and used Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines for the reporting of this systematic review. Most of the studies reinforced early initiation of the treatment by providing education to the patients and conducting their risk assessment. Strong evidence for the multidisciplinary treatment consisting of cognitive-behavioral therapy, psychoeducation, and physiotherapy is emphasized by some studies. More studies with a longer follow-up period are required to assess the effectiveness of intervention more accurately on depression. Regardless, this study will discuss guidelines and provide direction to physicians. It will help in developing future guidelines by addressing the clinical gaps in the implementation of these guidelines.
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