Hydrocortisone Combined with Vitamin C and Thiamine in the Treatment of Sepsis/Septic Shock: A Systematic Review with Meta-Analysis and Trial Sequential Analysis.

BACKGROUND: This study explored the efficacy of hydrocortisone combined with vitamin C and thiamine (HVT) in the treatment of sepsis/septic shock. METHODS: PubMed, EMBASE and Web of Science were searched (establishment of the database to October 31, 2022). The meta-analysis included randomized controlled trials (RCTs); comparing the efficacy of HVT regimen and placebo in the treatment of sepsis/septic shock. The Cochrane Handbook for Systematic Reviews of Interventions was used to assess the risk of bias. The Review Manager 5.4 software was used for meta-analysis, and the relative risk (RR), mean difference (MD) and 95% confidence intervals (CI) were then determined. Trial sequential analysis (TSA) was then conducted. RESULTS: Eight RCTs with 1,572 patients were identified. Meta-analysis showed that HVT regimen did not reduce all-cause (RR=0.96, 95% CI: 0.83 - 1.11, P=0.60), hospital (RR=1.03, 95% CI: 0.83 - 1.27, P=0.80) or intensive care unit (ICU) mortalities (RR=1.05, 95% CI: 0.86 - 1.28, P=0.65). Furthermore, there was no significant difference in the change of sequential organ failure assessment score, length of ICU stay, length of hospital stay, duration of the use of vasopressors, incidence of acute kidney injury and ventilator-free days between HVT and control groups. TSA showed that more trials are needed to confirm the results. CONCLUSIONS: HVT regimen did not reduce the mortality of patients with sepsis/septic shock and was not associated with a significant improvement in outcomes. The TSA result showed that more RCTs with high quality and large sample sizes are needed to further confirm the results.

Efficacy and Safety of Glucocorticoid in the Treatment of Acute Respiratory Distress Syndrome caused by Covid-19: A Systematic Review and Meta-Analysis.

BACKGROUND: Glucocorticoids are often used to treat acute respiratory distress syndrome (ARDS) and novel coronavirus disease 2019 (COVID-19). However, the efficacy and safety of glucocorticoids in the treatment of ARDS caused by COVID-19 are still controversial; therefore, we conducted this meta-analysis of the literature on this topic. METHODS: Four databases (PubMed, EMBASE, Cochrane Library, and Web of Science) were searched from the establishment of the databases to August 16, 2023. Randomized controlled trials (RCTs) and cohort studies that compared glucocorticoid versus standard treatment for ARDS caused by COVID-19 were included. The Newcastle-Ottawa Scale (NOS) checklist and the Cochrane Handbook for Systematic Reviews of Interventions were used to evaluate the risk of bias. Review Manager 5.4 software and STATA 17.0 were used for meta-analy-sis, and the relative risk (RR), mean difference, and 95% confidence intervals (CIs) were then determined. Results: A total of 17 studies involving 8592 patients were evaluated, including 14 retrospective studies and 3 RCTs. Sixteen studies reported data on all-cause mortality. The results of the meta-analysis showed that glucocorticoids did not reduce all-cause (RR, 0.96; 95% CI 0.82-1.13, P = .62) or 28-day (RR, 1.01; 95% CI 0.78-1.32, P = .93) mortality. Subgroup analysis showed that only methylprednisolone reduced all-cause mortality. No matter whether glucocorticoid use was early or delayed, high-dose or low-dose, long-term or short-term, no regimen reduced all-cause mortality. Furthermore, there were no significant differences in length of intensive care unit (ICU) stay, length of hospital stay, hyperglycemia, and ventilator-associated pneumonia (VAP); how-ever, glucocorticoids increased the number of ventilator-free days. CONCLUSIONS: Although methylprednisolone may reduce all-cause mortality from ARDS caused by COVID-19, this effect was not found with other types of glucocorticoids. At the same time, glucocorticoid use was associ-ated with more ventilator-free days, without increasing the incidence of hyperglycemic events or VAP. Con-sidering that almost all of the included studies were retrospective cohort studies, more RCTs are needed to confirm these findings.

Association between gene polymorphism of inflammatory factors, thrombogenic factors, and stress-related proteins and abdominal aortic aneurysm: A meta-analysis and systematic review.

BACKGROUND: Abdominal aortic aneurysm (AAA) is a deadly disease in the elderly population. Currently, the association between single nucleotide polymorphisms (SNPs) and the presence of AAAs has become a hot topic and is a concern for many researchers. METHOD: We performed a document retrieval in PubMed, EMBASE, and the Cochrane Library (to January 2020). A total of 17 case-control reports on SNPs of AAAs and eight SNPs of correlation factors were selected. All essential data, including race, age, country, criteria of AAA diagnosis, method of AAA measurement, method of genotype detection, name of SNPs, minor allele frequency (MAF), Hardy Weinberg equilibrium (HWE) of the control group, and number of cases and control groups were extracted by two reviewers independently. The fixed-effect model and random-effect model were used to calculate the overall odds ratios (ORs) and 95% confidence intervals (CIs). The association between selected SNPs and the presence of AAAs was evaluated under different genetic models (dominant, codominant, recessive, overdominant, and allele models). RESULTS: A total of 17 articles (sample size ranging from to 42-665 AAA cases and 49-2,297 controls) and 23 SNPs of related factors were identified. Eight SNPs were assessed in at least two studies and were selected for further meta-analysis. We found that the A allele of interleukin (IL)-10 (-1082 G/A) (OR: 1.35, 95% CI: 1.18-1.54, p < 0.0001) was a risk factor for AAAs under random and fixed-effect models. In addition, partial genetic models of these SNPs were confirmed to be related to the presence of AAA. Subgroup analysis revealed that haptoglobin (HP)-1 was a risk factor for AAAs (OR: 1.30, 95% CI: 1.04-1.63, p = 0.02) in the European population. No association was found between the occurrence of AAA and the other SNPs. CONCLUSION: In our current meta-analysis, we speculated that the genotype distribution of IL-10 (-1082 G/A) may be associated with the emergence of AAA.

Chinese ICU physicians' knowledge of antibiotic pharmacokinetics/pharmacodynamics (PK/PD): a cross-sectional survey.

BACKGROUND: Patients with sepsis have a high mortality rate, accumulated evidences suggest that an optimal antibiotic administration strategy based on pharmacokinetics/pharmacodynamics (PK/PD) can improve the prognosis of septic patients. Therefore, we assessed Chinese intensive care unit (ICU) physicians' knowledge about PK/PD. METHODS: In December 2019, we designed a questionnaire focused on Chinese ICU physicians' knowledge about PK/PD and collected the questionnaires after 3 months. The questionnaire was distributed via e-mail and WeChat, and was distributed to ICU doctors in 31 administrative regions of China except Hong Kong, Macao and Taiwan. The passing score was corrected by the Angoff method, and the ICU physicians' knowledge about PK/PD was analysed accordingly. RESULTS: We received a total of 1,309 questionnaires and retained 1,240 valid questionnaires. The passing score was 90.8, and the overall pass rate was 56.94%. The pass rate for tertiary and secondary hospitals was 59.07% and 37.19%, respectively. ICU physicians with less than 5 years of work experience and resident physician accounted for the highest pass rate, while those with between 5 to 10 years of work experience and attending accounted for the lowest pass rate. The majority of participants in the Chinese Critical Care Certified Course (5C) were from Jiangsu and Henan provinces, and they had the highest average scores (125.8 and 126.5, respectively). For Beijing and Shanghai, the average score was only 79.4 and 90.9, respectively. CONCLUSIONS: Chinese ICU physicians' knowledge about PK/PD is unsatisfactory. Therefore, it is essential to strengthen ICU physicians' knowledge about PK/PD.

Efficacy and safety of intravenous combined with aerosolised polymyxin versus intravenous polymyxin alone in the treatment of multidrug-resistant gram-negative bacterial pneumonia: A systematic review and meta-analysis.

Background: Previous studies have questioned the efficacy and safety of intravenous combined with aerosolised (IV + AS) polymyxin versus intravenous (IV) polymyxin alone in the treatment of patients with multidrug-resistant gram-negative bacterial (MDR-GNB) pneumonia. Therefore, we conducted a meta-analysis to evaluate the efficacy and safety of IV + AS polymyxin in the treatment of MDR-GNB pneumonia. Methods: We identified all relevant studies by searching the PubMed, EMBASE and Cochrane library databases from their inception to May 31, 2022. All included studies were evaluated using the Newcastle Ottawa scale (NOS) checklist. The summary relative risk (RR) and 95% confidence interval (CI) were used to determine the outcome differences between the IV + AS and the IV groups. Subgroup analysis was performed based on population, polymyxin dose and kinds of polymyxin. Results: A total of 16 studies were included in the meta-analysis. The IV + AS group had lower mortality (RR = 0.86, 95% CI: 0.77-0.97, P = 0.01) than the IV group. Subgroup analysis revealed that IV + AS polymyxin could reduce mortality only when used in low doses. Simultaneously, the IV + AS group outperformed the IV group in terms of clinical response rate, clinical cure rate, microbiological eradication and duration of mechanical ventilation. The duration of hospitalisation and the incidence of nephrotoxicity did not differ significantly between the two groups. Conclusions: IV + AS polymyxin is beneficial in the treatment of MDR-GNB pneumonia. It could lower patient mortality and improve clinical and microbial outcomes without increasing the risk of nephrotoxicity. However, retrospective analysis in the majority of studies and heterogeneity between studies implies that our findings must be interpreted carefully.

The Association Between Extracellular Matrix Metalloproteinase Inducer Polymorphisms and Coronary Heart Disease: A Potential Way to Predict Disease.

Extracellular matrix metalloproteinase inducer (EMMPRIN) had been reported to be involved in the occurrence and development of coronary heart disease (CHD) in previous studies. This study aimed to investigate whether single nucleotide polymorphisms of EMMPRIN and matrix metalloproteinase-9 (MMP-9) contributed to the onset and severity of CHD. One thousand seventy patients suspected to have CHD were enrolled into the study. Each patient had undergone coronary angiogram, and the severity of coronary artery stenosis was assessed by Gensini score. Eight hundred twelve patients were confirmed to have CHD, while 258 patients were selected as non-CHD control. All patients were genotyped for five EMMPRIN polymorphisms (rs8259, rs28915400, rs4919859, rs6758, and rs8637) and one MMP-9 polymorphism (rs3918242) by polymerase chain reaction-restriction fragment length polymorphism and confirmed by direct sequencing. EMMPRIN polymorphism rs8259 and MMP-9 polymorphism rs3918242 were found to be associated with CHD (rs8259: AT vs. AA, adjusted odds ratio [OR] = 2.038, adjusted 95% confidence interval [CI] = 1.080-3.847, p = 0.028; rs3918242: CT vs. CC, adjusted OR = 0.607, adjusted 95% CI = 0.403-0.916, p = 0.017, TT vs. CC, adjusted OR = 2.559, adjusted 95% CI = 1.326-4.975, p = 0.006). No crossover effects were observed although a single environmental or genetic factor had an impact on the occurrence of CHD. The value of the Gensini score revealed that severity of CHD decreased in the rs3918242 CT carriers in both the male and female population. Our study suggested that EMMPRIN rs8259 and MMP-9 rs3918242 polymorphisms may contribute to pathological process of CHD. It could play a critical role in the prediction of CHD.