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.
Introduction: Hemolytic Uremic Syndrome (HUS) is a condition characterized by progressive renal failure that is associated with microangiopathic hemolytic anemia and thrombocytopenia. It is a clinical syndrome which occurs as an immune reaction, most commonly after a gastrointestinal infection. Several studies have reported the prevalence of HUS among children but it is not well studied among adults. Studies have shown mortality rates ranging up to 20% and may go up to to 50% if HUS is complicated by end stage renal failure. There is limited data regarding HUS, especially among the adult population in regards to hospitalization trends and outcomes. In this study we aimed to describe the hospitalization trend, patient characteristics and in-hospital outcomes of HUS using a nationally representative database. Methods: Study cohort was from the Nationwide Inpatient Sample (NIS) for the years 2008-2017 for hospitalizations due to HUS by using International Classification of Diseases (9th/10th Editions) Clinical Modification diagnosis codes ICD-9-CM/ICD-10-CM). Other diagnosis and comorbidities were also identified by ICD-9/10-CM codes and Elixhauser comorbidity software. Our primary outcome was a discharge disposition following HUS hospitalization. We utilized multivariable survey logistic regression models to analyze and identify predictors of poor outcomes. Results: Between 2007-2018, a total of 8,043 hospitalizations occurred due to HUS. Hospitalization trend due to HUS increased from 528 (6.57%) in 2007 to 800 (9.95%) in 2013 and then reduced to 620 (7.7%) in 2018. Study cohort consisted of children <10 years of age (56.2%) followed by 18-65 years of age (24.7%). Out of total HUS patients, 74.4% were Caucasians and 59.3% were females. Overall in-hospital mortality of hospitalization due to HUS was 3.0%, and discharge to the facility was 15.7%. In trend analysis, the proportion of discharge to facility decreased from 23.1% in 2007 to 14.5% in 2018 but in-house mortality increased from 1% in 2007 to 3.2% in 2018. Median Length of hospital stay was 8-days (interquartile range 3-day to 15-days). Furthermore, in multivariable logistic regression analysis, age above 65 years (OR 2.5; 95%CI 1.4-5.8; p=0.0023), rural hospital (OR 17.9; 95%CI 8.9-36.1; p<0.001) and urban-non teaching hospital (OR 5.2; 95%CI 3.4-8.1; p<0.0001) and small-medium size hospitals were also associated with higher odds of discharge to facility among HUS patients. Conclusion: Our study estimates the epidemiology of hospitalizations due to HUS in the United States from a nationally representative database. In this study we observe that the burden of hospitalizations due to HUS has been increased over the study period. We also identified factors associated with poor discharge outcomes and some of which are modifiable. Further studies are warranted for developing strategies for better risk stratification of HUS patients to improve the overall outcomes. Disclosures No relevant conflicts of interest to declare.
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.
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.
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