Evaluating the Effectiveness and Safety of Evinacumab in Treating Hypercholesterolemia and Hypertriglyceridemia: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

BACKGROUND: Cardiovascular disease remains a significant global health concern, with high low-density lipoprotein cholesterol (LDL-C) levels contributing to an increased risk. Familial hypercholesterolemia (FH) further complicates its management, necessitating additional lipid-lowering therapies. Evinacumab, an angiopoietin-like protein 3 monoclonal antibody, has emerged as a potential treatment, particularly for patients with FH, by effectively reducing LDL-C and triglyceride levels. This meta-analysis aimed to evaluate the efficacy and safety of evinacumab across diverse patient populations. METHODS: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) criteria, relevant randomized controlled trials (RCTs) were systematically retrieved from multiple databases until November 24, 2023. The inclusion criteria were studies comparing evinacumab (at doses of 5 and 15 mg) to placebo, with outcomes focusing on lipid levels and adverse events. Standardized protocols were employed for data extraction and quality assessment, and statistical analysis was conducted using RevMan software. RESULTS: Four RCTs, involving 270 patients, were included in the analysis. The analysis revealed significant reductions in lipid markers, particularly with the 15-mg dose of evinacumab, including triacylglycerols (standard mean difference [SMD] = -6.09, 95% confidence interval [CI] - 14.53 to 2.36, P = 0.16), total cholesterol (SMD = - 6.20, 95% CI - 11.53 to - 0.88, P = 0.02), high-density lipoprotein cholesterol (SMD = - 0.79, 95% CI - 1.27 to - 0.31, P = 0.001), LDL-C (SMD = - 4.58, 95% CI - 9.13 to - 0.03, P = 0.05), apolipoprotein (Apo) B (SMD = - 4.01, 95% CI - 7.53 to - 0.46, P = 0.03), and Apo C3 (SMD = - 7.67, 95% CI - 12.94 to - 2.41, P = 0.004). Adverse event analysis revealed no significant association, indicating good tolerability. CONCLUSION: High-dose evinacumab (15 mg) consistently demonstrated efficacy in reducing cholesterol and other lipid markers, with favorable tolerability. Further research is warranted to comprehensively assess its safety and clinical effectiveness, emphasizing the need for additional data to support its use in managing cardiovascular disease.

Tailoring graphene-oxide and reduced-graphene-oxide with NaNO3 and CaCl2 catalysts with enhanced photo-catalytic degradation of methylene blue dye.

This study employed various experimental techniques to produce graphene oxide (GO) under different conditions, such as the inclusion or exclusion of NaNO3, and reduced graphene oxide (RGO) with or without the catalyst CaCl2. The procedure of decreasing RGO was carried out using the reducing agent NaBH4. Moreover, the prepared mixtures were utilized in the degradation process of methylene blue (MB) dye using photo-catalysis, with exposure to both ultraviolet (UV) light and sunlight. When exposed to UV and sunlight irradiation, WN-GO showed rapid and ecologically friendly breakdown of MB dye in comparison to N-GO. WN-GO exhibited exceptional adsorption capabilities, surpassing other tested materials like N-GO, WN-C-RGO and C-RGO. Although WN-C-RGO has demonstrated satisfactory performance in terms of photo-catalytic degradation, as the concentration-time graph of the MB dye revealed significant degradation, with a reduction of up to 90% and 62.5% under UV light and sunlight exposure, respectively. These results offer insightful information on the potential of graphene-based materials to address other environmental issues, particularly in the areas of water treatment.

Surgical strategies in acute subdural hematoma: a meta-analysis of decompressive craniectomy vs. craniotomy.

OBJECTIVE: Acute subdural hematoma (ASDH) stands as a significant contributor to morbidity after severe traumatic brain injuries (TBI). The primary treatment approach for patients experiencing progressive neurological deficits or notable mass effects is the surgical removal of the hematoma, which can be achieved through craniotomy (CO) or decompressive craniectomy (DC). Nevertheless, the choice between these two procedures remains a subject of ongoing debate and controversy. MATERIALS AND METHODS: We conducted a comprehensive literature review, utilizing prominent online databases and manually searching references related to craniotomy and craniectomy for subdural hematoma evacuation up to November 2023. Our analysis focused on outcome variables such as the presence of residual subdural hematoma, the need for revision procedures, and overall clinical outcomes. RESULTS: We included a total of 11 comparative studies in our analysis, encompassing 4269 patients, with 2979 undergoing craniotomy and 1290 undergoing craniectomy, meeting the inclusion criteria. Patients who underwent craniectomy displayed significantly lower scores on the Glasgow Coma Scale (GCS) during their initial presentation. Following surgery, the DC group exhibited a significantly reduced rate of residual subdural (P = 0.009). Additionally, the likelihood of a poor outcome during follow-up was lower in the CO group. Likewise, the mortality rate was lower in the CO group compared to the craniectomy group (OR 0.63, 95% CI 0.41-0.98, I2 = 84%, P = 0.04). CONCLUSION: Our study found that CO was associated with more favorable outcomes in terms of mortality, reoperation rate, and functional outcome while DC was associated with less likelihood of residual subdural hematoma. Upon further investigation of patient characteristics who underwent into either of these interventions, it was very clear that patients in DC cohort have more serious and low pre-op characteristics than the CO group. Nonetheless, brain herniation and advanced age act as independent factor for predicting the outcome irrespective of the intervention.

Assessing the impact of pre-hospital airway management on severe traumatic Brain injury: A systematic review and Meta-analysis.

OBJECTIVE: This study aimed to assess the impact of establishing a pre-hospital definitive airway on mortality and morbidity compared with no prehospital airway in cases of severe traumatic brain injury (TBI). BACKGROUND: Traumatic brain injury (TBI) is a global health concern that is associated with substantial morbidity and mortality. Prehospital intubation (PHI) has been proposed as a potential life-saving intervention for patients with severe TBI to mitigate secondary insults, such as hypoxemia and hypercapnia. However, their impact on patient outcomes remains controversial. METHODS: A systematic review and meta-analysis were conducted to assess the effects of prehospital intubation versus no prehospital intubation on morbidity and mortality in patients with severe TBI, adhering to the PRISMA guidelines. RESULTS: 24 studies, comprising 56,543 patients, indicated no significant difference in mortality between pre-hospital and In-hospital Intubation (OR 0.89, 95% CI 0.65-1.23, p = 0.48), although substantial heterogeneity was noted. Morbidity analysis also showed no significant difference (OR 0.83, 95% CI 0.43-1.63, p = 0.59). These findings underscore the need for cautious interpretation due to heterogeneity and the influence of specific studies on the results. CONCLUSION: In summary, an initial assessment did not reveal any apparent disparity in mortality rates between individuals who received prehospital intubation and those who did not. However, subsequent analyses and randomized controlled trials (RCTs) demonstrated that patients who underwent prehospital intubation had a reduced risk of death and morbidity. The dependence on biased observational studies and the need for further replicated RCTs to validate these findings are evident. Despite the intricacy of the matter, it is crucial to intervene during severe airway impairment.

Morphological analysis and grain size distribution of SnO2 nanoparticles via digital image processing across diverse calcination temperatures.

This study presents a comprehensive image analysis of the SnO2 nanoparticles synthesised through calcination at diverse temperatures, which enables an estimation of grain size distribution (GSD) from field-emission scanning electron microscopy (FE-SEM) images. Even though FE-SEM images could provide us with a lot of information about sample differences, we can learn more and perform a more accurate analysis of them by using quantitative data obtained by our image processing application. The digital image processing techniques used in this research provide a detailed analysis of the nanoparticles' size and shape, enabling a deeper understanding of their unique characteristics. The results reveal the significant impact of calcination temperature on the morphology of the nanoparticles, with changes in grain size and grain size distribution observed at varying temperatures.

Unraveling the terpene synthase family and characterization of BsTPS2 contributing to (S)-( +)-linalool biosynthesis in Boswellia.

Boswellia tree bark exudes oleo-gum resin in response to wounding, which is rich in terpene volatiles. But, the molecular and biochemical basis of wound-induced formation of resin volatiles remains poorly understood. Here, we combined RNA-sequencing (RNA-seq) and metabolite analysis to unravel the terpene synthase (TPS) family contributing to wound-induced biosynthesis of resin volatiles in B. serrata, an economically-important Boswellia species. The analysis of large-scale RNA-seq data of bark and leaf samples representing more than 600 million sequencing reads led to the identification of 32 TPSs, which were classified based on phylogenetic relationship into various TPSs families found in angiosperm species such as TPS-a, b, c, e/f, and g. Moreover, RNA-seq analysis of bark samples collected at 0-24 h post-wounding shortlisted 14 BsTPSs that showed wound-induced transcriptional upregulation in bark, suggesting their important role in wound-induced biosynthesis of resin volatiles. Biochemical characterization of a bark preferentially-expressed and wound-inducible TPS (BsTPS2) in vitro and in planta assays revealed its involvement in resin terpene biosynthesis. Bacterially-expressed recombinant BsTPS2 catalyzed the conversion of GPP and FPP into (S)-( +)-linalool and (E)-(-)-nerolidol, respectively, in vitro assays. However, BsTPS2 expression in Nicotiana benthamiana found that BsTPS2 is a plastidial linalool synthase. In contrast, cytosolic expression of BsTPS2 did not form any product. Overall, the present work unraveled a suite of TPSs that potentially contributed to the biosynthesis of resin volatiles in Boswellia and biochemically characterized BsTPS2, which is involved in wound-induced biosynthesis of (S)-( +)-linalool, a monoterpene resin volatile with a known role in plant defense.

Association between elevated lactate and clinical outcomes in adults with diabetic ketoacidosis.

PURPOSE: To assess the occurrence of hyperlactatemia among patients admitted to the intensive care unit (ICU) with diabetic ketoacidosis (DKA), and effect on in-hospital mortality. MATERIALS AND METHODS: A retrospective, multicentre, cohort study of adult patients admitted to ICU with a primary diagnosis of DKA in Australia and New Zealand, utilising a pre-existing dataset. The primary exposure variable was lactate, dichotomised into normolactatemia (lactate <2.0 mmol/L) and hyperlactatemia (lactate ≥ 2.0 mmol/L) groups. The primary outcome was in-hospital mortality. Secondary outcomes included ICU and hospital length of stay (LOS), requirement for ventilation, renal replacement therapy (RRT) and inotropes. RESULTS: The final dataset included 9061 patients. Hyperlactatemia was associated with in-hospital mortality (Odds Ratio [OR] 1.785 (95% CI 1.122-2.841, p = 0.014), hospital LOS (Geometric mean ratio [GMR] 1.063, 95% CI 1.025-1.103, p = 0.001), ICU LOS (GMR 1.057, 95% CI 1.026-1.09. p < 0.001), RRT (OR 2.198, 95% CI 1.449-3.334, p < 0.001) and inotropes (OR 1.578, 95% CI 1.311-1.899, p < 0.001). These associations persisted in Type 2 but not Type 1 diabetics. CONCLUSIONS: Hyperlactatemia in patients admitted to ICU with DKA is associated with higher mortality, longer hospital and ICU LOS, and higher rates of mechanical ventilation, RRT and inotropes.

Efficacy and safety of steroids for chronic subdural hematoma: A systematic review and meta-analysis.

Background: Chronic subdural hematoma (CSDH) is a condition characterized by the accumulation of fluid, blood, and blood breakdown products between the brain's arachnoid and dura mater coverings. While steroids have been explored as a potential treatment option, their efficacy and safety remain uncertain. This meta-analysis and systematic review aimed to assess the impact of steroids on CSDH management, including mortality, recurrence, complications, and functional outcomes. Methods: We conducted a comprehensive literature search in major electronic databases up to June 2023, following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and Cochrane Handbook for Systematic Reviews and Interventions. Inclusion criteria encompassed adult patients with CSDH, the use of steroids as monotherapy or adjuvant therapy, and clearly defined outcomes. Randomized controlled trials and cohort studies meeting these criteria were included in the study. Results: The initial search yielded 4315 articles, with 12 studies meeting the inclusion criteria. Our findings indicate a non-significant trend toward reduced mortality with steroids in combination with standard care (Odds ratios [OR] = 0.66, 95% confidence interval [CI] 0.20-2.18). However, substantial heterogeneity was observed (I2 = 70%). Sensitivity analysis, excluding influential studies, suggested a potential increased mortality risk associated with steroids (OR = 1.47, 95% CI 0.87-2.48). Steroids showed a possible benefit in reducing the recurrence of CSDH (OR = 0.58, 95% CI 0.20-1.67), but with significant heterogeneity (I2 = 89%). No clear advantage of steroids was observed in terms of functional outcomes at three months (modified Rankin scale scores). Furthermore, steroids were associated with a significantly higher incidence of adverse effects and complications (OR = 2.17, 95% CI 1.48-3.17). Conclusion: Steroids may have a potential role in reducing CSDH recurrence but do not appear to confer significant advantages in terms of mortality or functional outcomes. However, their use is associated with a higher risk of adverse effects and complications. Given the limitations of existing studies, further research is needed to refine the role of steroids in CSDH management, considering patient-specific factors and treatment protocols.

Outcomes of Prolonged ICU Stay for Patients Undergoing Cardiac Surgery in Australia and New Zealand.

OBJECTIVE: To determine the effect of intensive care unit (ICU) length of stay (LOS) on hospital mortality and non-home discharge for patients undergoing cardiac surgery over a 16-year period in Australia and New Zealand. DESIGN: A retrospective, multicenter cohort study covering the period January 1, 2004 to December 31, 2019. SETTING: One hundred one hospitals in Australia and New Zealand that submitted data to the Australia New Zealand Intensive Care Society Adult Patient Database. PARTICIPANTS: Adult patients (aged >18) who underwent coronary artery bypass grafting, valve surgery, or combined valve + coronary artery surgery. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The authors analyzed 252,948 cardiac surgical patients from 101 hospitals, with a median age of 68.3 years (IQR 60-75.5), of whom 74.2% (187,632 of 252,948) were male patients. A U-shaped relationship was observed between ICU LOS and hospital mortality, with significantly elevated mortality at short (<20 hours) and long (>5 days) ICU LOS, which persisted after adjustment for illness severity and across clinically important subgroups (odds ratio for mortality with ICU LOS >5 days = 3.21, 95% CI 2.88-3.58, p < 0.001). CONCLUSIONS: Prolonged duration of ICU LOS after cardiac surgery is associated with increased hospital mortality in a U-shaped relationship. An ICU LOS >5 days should be considered a meaningful definition for prolonged ICU stay after cardiac surgery.

Recruitment characteristics of randomised trials in critical care: A systematic review.

BACKGROUND/AIMS: To summarise the temporal trends of recruitment and methodological characteristics of critical care randomised controlled trials with the primary outcome of mortality. METHODS: PubMed was searched for articles meeting inclusion and exclusion criteria. Randomised controlled trials, with primary outcome of mortality, of adult and paediatric critical care patients treated in an intensive care unit, were included. Neonatal intensive care unit trials, non-English publications and conference proceedings or abstracts without full-length publications were excluded. Duplicate literature search, article selection and quality assessment were performed by two reviewers with disputes resolved through discussion. Data were extracted into a custom-designed Research Electronic Data Capture database. RESULTS: The search identified 67,199 records of which 230 were included. The annual number of critical care randomised controlled trials published increased gradually over a 30-year period from 0 in 1990 to 19 in 2014 with stabilisation at 8-11 between 2015 and 2020. Twenty-seven percent of randomised controlled trials were low risk in all categories using the Cochrane Risk of Bias tool. Methodological characteristics such as registration on clinical trials registries and data safety monitoring committee presence significantly (p < 0.001) increased over time. The median recruitment was 376 patients (interquartile range 125-895) with significant increase (p = 0.002) from 62 (interquartile range: 33-486) in 1991 to 725 (interquartile range: 537-2600) in 2020. This was accompanied by an increase in recruitment times. Thus overall, recruitment rates did not increase. Early cessation occurred in 23% (54/230) of randomised controlled trials with no temporal trend. CONCLUSION: The number, size and some methodological qualities of critical randomised controlled trials with primary outcome of mortality have increased over time, but rates of recruitment and early cessation have been unchanged.

Battlefield Acupuncture Use for Perioperative Anesthesia in Veterans Affairs Surgical Patients: A Single-Center Randomized Controlled Trial.

Introduction: The risks from opioid use are well known in and mandate nonpharmacological modalities for the management of postoperative pain. The aim of this study was to investigate the effectiveness of battlefield acupuncture (BFA) as an adjunct therapy for postoperative pain in U.S. veteran patients undergoing major surgery under general anesthesia. Methods: Patients undergoing major surgery performed under general anesthesia from June 2017 to June 2018 were enrolled in the study. Patients were randomly assigned to receive either BFA or sham acupuncture. Outcomes such as pain intensity measured by visual analog scale score, opioid consumption, and the incidence of analgesia-related adverse effects were compared between the study groups. Results: A total of 72 subjects were included in this study (36 subjects in each study group). The median 24-h opioid postoperative consumption measured in morphine milligram equivalent (MME) was lower in the BFA group compared to the sham acupuncture group (18.3 [±12.2] MME vs. 38.6 [±15.9] MME, p < 0.001). Pain intensity reported by patients at 6, 12, 18, and 24 h postoperatively was lower in the BFA group compared to the sham acupuncture group. The incidence of postsurgical nausea and vomiting was lower in patients receiving BFA compared to patients receiving sham acupuncture. There were no intergroup differences in terms of postoperative anxiety or hospital length of stay. Conclusion: The results from this study reveal the potential clinical benefits of using BFA for reducing pain intensity and opioid requirements in surgical patients.

Early Albumin Exposure After Cardiac Surgery.

OBJECTIVES: To determine whether the early use of albumin after cardiac surgery in the first 24 hours in the intensive care unit (ICU) is associated with reduced mortality. DESIGN: A single-center nonrandomized retrospective cohort study using the Medical Information Mart in Intensive Care IV database. SETTING: A single cardiothoracic ICU in the United States during a period between 2008 to 2019. PARTICIPANTS: Patients undergoing valvular and/or cardiac bypass graft surgeries. INTERVENTIONS: Albumin administered during the first 24 hours of the ICU admission. MEASUREMENTS AND MAIN RESULTS: A total of 8,136 patients were included in this study, of whom 4,444 (54.6%) received albumin at any stage during the first 24 hours of ICU admission, and 69 (1.6%) of those patients died. The patient population exposed to albumin had higher comorbidities and illness severity compared to the no-albumin group. Patients exposed to albumin during the first 24 hours of ICU admission had a statistically significant reduction in mortality (odds ratio [OR], 0.68; 95% confidence interval [CI], 0.48-0.97, p < 0.05) after adjustment for age, the Oxford Acute Severity of Illness Score, and the Charlson comorbidity index. A sensitivity analysis of patients who received albumin at any stage during ICU admission showed increased mortality (OR, 1.93; 95% CI, 1.26-3.07, p < 0.01). Patients exposed to albumin had a significant increase in adjusted ICU length of stay (LOS) (geometric mean ratio 1.09; 95% CI, 1.05-1.10, p = < 0.001) and hospital LOS (geometric mean ratio 1.08; 95% CI, 1.05-1.10, p < 0.001). CONCLUSIONS: Exposure to albumin in the first 24 hours after cardiac surgery is associated with a reduction in adjusted hospital mortality and an increase in both hospital and ICU lengths of stay.