Saudi Cultural Missions Theses & Dissertations
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Item Restricted Restrictive Versus Liberal or Standard Intravenous Fluid Administration in Patients with Sepsis or Septic Shock: A Systematic Review(Queen Mary University of London, 2024-07-31) Khogeer, Tariq; Prowle, JohnSepsis and septic shock are leading causes of morbidity and mortality worldwide, with effective management being critical to improving patient outcomes. Intravenous (IV) fluid resuscitation is a cornerstone of treatment in septic patients; however, the optimal fluid management strategy remains controversial. This systematic review examines the impact of restrictive versus liberal or standard fluid resuscitation strategies on mortality in patients with sepsis or septic shock. The review included eight randomized controlled trials (RCTs) involving 2,375 patients. The primary outcome was mortality within 90 days. Secondary outcomes included the use of mechanical ventilation, vasopressor requirements, renal replacement therapy, and the occurrence of adverse events such as limb ischemia and acute kidney injury. The findings suggest no significant difference in mortality between restrictive and liberal fluid administration. However, restrictive strategies may reduce the need for mechanical ventilation and vasopressor support. These results highlight the need for individualized fluid resuscitation strategies in septic patients, tailored to clinical circumstances. Further large-scale studies are recommended to confirm these findings and optimize fluid management protocols.13 0Item Restricted MAJOR ADVERSE EVENTS IN CRITICALLY ILL PATIENTS WITH ACUTE RESPIRATORY DISTRESS SYNDROME(Saudi Digital Library, 2021) Alenezi, Faraj; Thickett, David; Parekh, Dhruv; Mahida, Rahul; Patel, JaiminAcute kidney injury (AKI) is common among patients with COVID-19 or sepsis. The incidence of AKI may increase when these patients develop acute respiratory distress syndrome (ARDS), which is often associated with poorer patient outcomes and higher mortality rates. Major adverse kidney events (MAKEs) - a composite of the need for renal replacement therapy (RRT), a decline in eGFR of <75% from baseline, or all- cause mortality - are considered a reliable long-term measure of AKI's impact on patient outcomes. This thesis aimed to evaluate the existing evidence regarding the incidence and risk factors of AKI in COVID-19 patients with ARDS. Additionally, it sought to determine the incidence and clinical risk factors of MAKE-365 in patients with AKI, both with and without COVID-19 ARDS. The thesis also examined the associations between novel kidney biomarkers (including plasma Cystatin C, urinary NGAL, urinary [TIMP- 2]*[IGFBP-7], and urinary CCL-14) and MAKE-365 in ICU patients with sepsis and AKI. Lastly, it evaluated the predictive capabilities of these kidney biomarkers in combination with clinical predictive models for MAKE-365. Firstly, a systematic review and meta-analysis were conducted to examine the incidence and risk factors of AKI in COVID-19 patients with ARDS. This review, which included 31 studies, found a higher incidence of AKI in COVID-19 patients with ARDS compared to those without. The study identified several risk factors associated with worse outcomes, including advanced age, male gender, and pre-existing conditions such as hypertension, diabetes, obesity, and CKD. Secondly, a retrospective cohort study was carried out on ARDS patients to assess the occurrence of MAKEs up to 365 days post-ICU admission in both non-COVID-19 and COVID-19 cohorts. The incidence of MAKE-365 was more common in the non- COVID-19 cohort. CKD and high bilirubin levels were identified as predictors for MAKE-365 in both cohorts, with additional risk factors such as older age and diabetes in the COVID-19 cohort and lower albumin levels in the non-COVID-19 cohort. Finally, another retrospective cohort study was conducted to assess MAKE-365 development and evaluate the predictive ability of kidney biomarkers for MAKE-365 in septic patients, regardless of ARDS status. The prevalence of MAKE-365 was higher in septic patients with AKI, irrespective of ARDS status. Among the evaluated biomarkers, urinary [TIMP-2]*[IGFBP-7] showed the most promise for predicting MAKE-365, particularly when combined with the clinical prediction model. Overall, this thesis underscores the importance of identifying patients at risk of MAKE- 365 development in critically ill patients using clinical predictors in conjunction with kidney biomarkers. However, the utility of these biomarker combinations must be confirmed in larger, external prospective cohorts to ensure the findings' generalizability and specificity to the patient population used in this study.15 0Item Restricted Identification and Functional Characterization of Novel Variants Associated with Sepsis Identified by Whole Exome Sequencing(Saudi Digital Library, 0098-11-04) Alsaif, Hessa Saad; Knight, Julian; Jia, AliciaBackground Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection. It is a leading cause of global mortality. Although sepsis is not considered a classic monogenic trait, there is strong evidence of the role of genetics in its susceptibility. Methods and Results This project uses the previously collected sepsis-affected cohort of 484 whole-exome sequenced (WES) samples to bring insights into genetics of sepsis. The two variants in GNLY gene encoding for antimicrobial peptide granulysin, NM_006433.5:c.255+2T>C and NM_006433.5:c.304C>T, have been prioritised using in silico variant pathogenicity prediction tools for further in vitro evaluation. These variants were present in three patients from sepsis cohort. The criteria for prioritisation were the rarity of the variants in non-affected population, the high impact consequences of the variants on GNLY transcripts and proteins, and the essential role of the GNLY gene as a key component of the immune response. NM_006433.5:c.304C>T variant introduces a premature stop codon and is predicted to lead to truncation of GNLY protein by third: from 148 aa to 102 aa. NM_006433.5:c.255+2T>C variant was predicted to affect splicing of exons 3-4 of GNLY transcript. The presence of the variants in three patients from the cohort in a heterozygous state has been confirmed through Sanger sequencing. In vitro ExonTrap minigene assays have confirmed that NM_006433.5:c.255+2T>C variant leads to aberrant splicing. It has been also investigated whether the two variants are presented in compound heterozygote state using cloning assay. The overall conclusion was that the variants are not likely to be present in the compound heterozygote state in two patients. Conclusion Potential of GNLY being a novel sepsis-susceptibility gene, caveats of variant pathogenicity predictions and the potential genetic mechanisms by which the two variants can contribute to the genetics of susceptibility of sepsis are further discussed.12 0Item Restricted IV Vitamin C as an Adjunctive Therapy in Sepsis and Sepsis Shock.(Saudi Digital Library, 2023-10) Alawad, Norah; Hart, RobertIn my systematic literature search, I aim to thoroughly explore the use of vitamin C, as an adjunctive therapy, in the management of sepsis and septic shock. Since the latter possess significant challenges in the practice of critical care, I believe this necessitates the exploration of other supportive therapies that enhances the patients’ outcomes. By conducting a thorough search in multiple databases, my project investigated the plausibility of using vitamin C in sepsis and septic shock and how this may influence different outcomes, most importantly, the mortality rate. Furthermore, my project will dive into a comprehensive examination of high quality randomised controlled trials (RCTs), outlining in details the process of the critical appraisal and how my conclusion is based on this analysis. Finally, the findings of this project will shed the light on the implications, future recommendations, and current unanswered questions related to the use of vitamin C. This will potentially lead to an enhancement of the patients’ care and providing innovative approaches for upcoming research as well as improving the treatment protocols in the critical care settings.13 0