Saudi Cultural Missions Theses & Dissertations
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Item Restricted Investigating TIMP-1 as a Potential Biomarker and Target in Acute Lung Injury(University of Georgia, 2024-05) Almuntashiri, Sultan; Zhang, DuoAcute respiratory distress syndrome (ARDS) confers high morbidity and mortality, with a death rate reaching 40%. Several etiology factors lead to ARDS, including trauma, multiple blood transfusion, sepsis, bacterial pneumonia as well as viral pneumonia like influenza A virus (IAV) and corona virus disease (COVID-2019). Tissue inhibitor of metalloproteinase-1 (TIMP-1) is a physiologic inhibitor of the matrix metalloproteinases (MMPs) that regulate adaptive immune responses and located on the X chromosome. This thesis collectively aimed to evaluate the prognostic role of circulating TIMP-1 in aspect of sex difference, investigate if TIMP-1 is a downstream target of the estrogen signaling pathway and the regulation and function of TIMP-1 during lung injury. TIMP-1 was measured from plasma samples of healthy human subjects, patients with acute lung injury caused by IAV infection, COVID-2019 or other etiologies using enzyme-linked immunosorbent assay (ELISA) method. Normal lung fibroblasts IMR-90 and MLg were investigated in response to estrogen treatment to evaluate the TIMP-1 expression. Wild type and Timp-1 deficient mice were employed to study the possibility of TIMP-1 as a novel therapeutic target for lung injury. Our results showed that circulating TIMP-1 appeared to be a promising predictor of severity and mortality outcomes like ventilator-free days (VFDs), ICU-free days and death at 30 and 90-day among females with ARDS. Fibroblasts treated with estrogens confirmed that TIMP-1 is significantly linked to estrogen, and luciferase reporter assay indicated that ERα not ERβ regulates TIMP-1 promoter activity. Lastly, Timp-1 deficiency protects mice from IAV- induced weight loss, mortality, and lung injury.4 0Item Restricted The Impact of Positive End-Expiratory Pressure on Mortality Rate among Patients with Acute Respiratory Distress Syndrome(Saudi Digital Library, 2023-08-23) Alrayes, Mashael; Hunter, JoannaBackground: High levels of Positive End-Expiratory Pressure (PEEP) have been found to potentially increase lung volume and improve oxygenation in patients with Acute Respiratory Distress Syndrome (ARDS). They also increase the risk of lung injury caused by overdistention. ARDS has a high mortality rate; however, the impact of increased PEEP on clinical outcomes in patients with ARDS is variable. Aim: The aim of this dissertation is to examine the available studies that compared the impact of high PEEP levels with that of low PEEP levels on the reduction of ARDS mortality rates. Methods: A comprehensive search of literature on Randomised Controlled Trials (RCTs) and cohort studies was conducted using four databases—MEDLINE, Embase, Cochrane Library and CINAHL (EBSCOhost) from the last 15 years to June 2023. The inclusion criteria were studies that examined the ARDS mortality rate in patients subjected to high PEEP levels (as the intervention group) and to low PEEP levels (as the control group). An automation tool was utilised, along with duplicates removal options through Endnote and Rayyan reference management tools. Results: A total of 1637 studies were identified. They were screened through the evaluation of their titles and abstracts and then, of their full text, in accordance with predetermined inclusion and exclusion criteria. Finally, seven studies were selected and included in this dissertation. Conclusion: The mortality reduction in patients with ARDS who received higher levels of PEEP did not differ significantly from that in patients with ARDS who received lower levels of PEEP.33 0Item Restricted ECMO in Management of Patients With ARDS in The Intensive Care Unit, Systematic Review(2022) Ahmed, Asiri; Zolfaghari, ParjamPurpose: The purpose of this study was to evaluate the efficacy of venovenous extracorporeal membrane oxygenation (ECMO) in comparison to conventional therapy in patients diagnosed with severe acute respiratory distress syndrome (ARDS). Methods: I carried out a systematic review of randomised controlled trials (RCTs) that were carried out after January 1st 2000, with the purpose of comparing extracorporeal membrane oxygenation (ECMO) to conventional therapy in patients with severe ARDS. Results: I were able to locate two randomised controlled trials (CESAR and EOLIA), and I merged the data from 429 patients. On day 90, 77 of the 214 patients in the ECMO-group (36%) and 103 of the 215 patients in the control group (48%) had passed away. 36 (17%) of the control patients required emergency cardiopulmonary bypass (ECMO) (35 in EOLIA and 1 in CESAR). The treatment failure at 90 days was defined as death in the ECMO-group and either death or crossover to ECMO in the control group. Patients who were randomly assigned to get ECMO had a greater number of days in which they survived outside of the intensive care unit and were free of respiratory, cardiovascular, renal, and neurological failure. The only meaningful treatment-covariate interaction found in subgroups was a decreased death rate with ECMO in patients who had failure of two organs or less at the time of randomization. Conclusions: In patients with severely severe ARDS, neither the EOLIA study nor the CESAR study were able to successfully demonstrate that ECMO resulted in a significant improvement in the mortality rate after 60 days.34 0Item Restricted The Impact of Prone Position on Mechanically Ventilated Patients with Covid19-ARDS, systematic review(Abdulhakeem Alotaibi, 2023-03-22) Alotaibi, Abdulhakeem; Zolfaghari, Parjam; Abu Kursi, AdelBackground Over the last few years coronavirus has spread rampantly, effecting each nation in various ways. This virus causes acute respiratory syndrome (SARS-CoV-2) which must be aided by mechanical respiration. Prone position ventilation is a known technique that enhances oxygenation in COVID-19 patients suffering from serious acute respiratory distress syndrome (ARDS). Methodology This study conducted a systematic analysis of randomised controlled trials (RCTs) that commenced from January 2019 and onwards. The study’s purpose was to measure the effectiveness of prone position applications on individuals with mechanical ventilation who suffered from COVID-19 induced ARDS compared to those administered the supine position treatment. Results Research elected two sufficient randomised controlled trials for this study. Both studies included 452 patients who showed that application of the prone position technique correlates with a substantial enhancement in PaO2/FiO2, considerable rise in static lung compliance and insignificant variations in the extubation rate. This suggests that the prone position approach causes minimal complexities, thus is innocuous for COVID-19 patients. Prone emplacement did not considerably reduce the death rate during the 60 day time period or the length of hospital admission. Moreover, there was no meaningful influence on the 30 day period without invasive or non-invasive mechanical ventilation. No effect was stated during the 60 days without critical care observation or hospitalisation. The majority of trials explained that there was discomfort or musculoskeletal pain from the prone emplacement and desaturation. Conclusion Prone position application for COVI-19 induced ARDS is a safe and effective practice in patients with severe hypoxemic respirational malfunction. Despite prone posture being ineffective in limiting endotracheal intubation requirements compared to typical care that did not implement the prone emplacement, the clinical advantages of prone posture are significant.28 0