Efficacy and safety of azilsartan medoxomil in the treatment of hypertension: a systematic review and meta-analysis.

Background: Angiotensin II receptor blockers (ARBs) are utilized for the management of hypertension and diabetes. Previous meta-analyses suggested that azilsartan medoxomil (AZL-M) improved blood pressure (BP) reduction, but there were no safety findings or suggestions for patients with hypertension or diabetes. Methods: We performed an efficacy and safety meta-analysis of randomized controlled trials (RCTs) evaluating AZL-M therapy for reducing BP in patients with hypertension. Patients with hypertension complicated by diabetes were analyzed. The relevant literature was searched in English and Chinese databases for RCTs involving AZL-M in hypertension. Efficacy variables included the change from baseline in the 24-h mean systolic/diastolic BP measured by ambulatory BP monitoring, the change from baseline in clinic systolic/diastolic BP, and responder rates. Safety variables included total adverse events (AEs), serious AEs, AEs leading to discontinuation, and AEs related to the study drug. The raw data from the included studies were utilized to calculate the odds ratio (OR) for dichotomous data and the mean difference (MD) for continuous data, accompanied by 95% confidence intervals (CIs). Statistical analysis was performed using R software. Results: A total of 11 RCTs met the inclusion criteria, representing 7,608 patients, 5 of whom had diabetes. Pooled analysis suggested a reduction in BP among patients randomized to 40 mg of AZL-M vs. control therapy [24-h ambulatory blood pressure monitoring (ABPM) mean systolic blood pressure (SBP) (MD: -2.85 mmHg), clinic SBP (MD: -3.48 mmHg), and clinic diastolic blood pressure (DBP) (MD: -1.96 mmHg)] and for 80 mg of AZL-M vs. control therapy [24-h ABPM mean SBP (MD: -3.59 mmHg), 24-h ABPM mean DBP (MD: -2.62 mmHg), clinic SBP (MD: -4.42 mmHg), clinic DBP (MD: -3.09 mmHg), and responder rate (OR: 1.46)]. There was no difference in the reduction of risks, except for dizziness (OR: 1.56) in the 80-mg AZL-M group or urinary tract infection (OR: 1.82) in the 40-mg AZL-M group. Analysis of patients with diabetes revealed that AZL-M can provide superior management, while safety and tolerability were similar to those of control therapy. Conclusions: AZL-M appears to reduce BP to a greater extent than dose-control therapy and does not increase the risk of adverse events in patients with hypertension and diabetes compared with placebo. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=464284, identifier PROSPERO CRD42023464284.

Optimization of Early Antimicrobial Strategies for Lung Transplant Recipients Based on Metagenomic Next-Generation Sequencing.

The management of perioperative antibiotic options after lung transplantation varies widely around the world, but there is a common trend to limit antibiotic use duration. Metagenomic next-generation sequencing (mNGS) has become a hot spot in clinical pathogen detection due to its precise, rapid, and wide detection spectrum of pathogens. Thus, we defined a new antibiotic regimen adjustment strategy in the very early stage (within 7 days) after lung transplantation mainly depending on mNGS reports combined with clinical conditions to reduce the use of antibiotics. To verify the clinical effect of the strategy, we carried out this research. Thirty patients who underwent lung transplantation were finally included, whose information including etiology, antibiotic adjustment, and the effect of our strategy was recorded. Lung transplant recipients in this study were prescribed with initial antibiotic regimen immediately after surgery; their antibiotic regimens were adjusted according to the strategy. According to our study, the entire effectiveness of the strategy was 90.0% (27/30). Besides, a total of 86 samples containing donor lung tissue, recipient lung tissue, and bronchoalveolar lavage fluid (BALF) were obtained in this study; they were all sent to mNGS test, while BALF was also sent to pathogen culture. Their results showed that the positive rate of BALF samples was higher (86.67%) than that of donor's lung tissue (20.0%) or recipient's lung tissue (13.33%) by mNGS test, indicating BALF samples are more valuable than other clinical samples from early postoperative period to guide the early adjustment of antibiotics after lung transplantation. It is effective for mNGS combined with traditional methods and clinical situations to optimize antibiotic regimens in lung transplantation recipients within 7 days after surgery.

[Prognostic value of transthoracic lung ultrasound comet-tail and extravascular lung water index in septic patients].

OBJECTIVE: To evaluate the prognostic value of transthoracic lung ultrasound comet-tail and extravascular lung water index (EVLWI) in septic patients. METHODS: A prospective cohort study was conducted. Sixty septic patients admitted to department of intensive care unit (ICU) of Sichuan Provincial People's Hospital from November 2016 to October 2019 were enrolled. The EVLWI and pulmonary vascular permeability index (PVPI) were determined by pulse-indicated continuous cardiac output (PiCCO) system at 0, 24, 48 and 72 hours. At the same time, the numbers of comet tail signs in both lungs (parasternal, midclavicular, axillary to midaxillary) were collected by chest ultrasound. Moreover, arterial blood gas analysis, such as pH value, central venous-to-arterial carbon dioxide difference (Pcv-aCO2), central venous oxygen saturation (ScvO2), blood lactic acid (Lac), PaO2/FiO2 were measured. Pearson correlation analysis was performed between the number of comet-tail sign and EVLWI. Multivariate Logistic regression model was used to analyze the relationship between the number of comet-tail sign, EVLWI and prognosis. Receiver operator characteristic curve (ROC curve) was drawn to predict the prognosis. RESULTS: There were 43 males and 17 females in 60 septic patients. The average age was (64.3±15.5) years old (range: 31-83 years old). There were 35 cases with pulmonary infection, 10 cases with abdominal infection, 6 cases with urinary tract infection, 3 cases with skin and soft tissue infection, 3 cases with intestinal infection, 1 case with meningitis, 1 case with cellulitis and 1 case with multiple injury. Acute respiratory distress syndrome (ARDS) occurred with 8 patients; 40 patients (66.7%) survived and 20 patients (33.3%) died on day 28. Pearson correlation analysis showed that the number of comet-tail sign was positively correlated with EVLWI (r = 0.944, P < 0.001). There was significant difference in the number of comet-tail signs among sepsis patients with different primary infection sites (H = 17.714, P < 0.001). The number of comet-tail signs in sepsis patients with pulmonary infection [19 (13, 27)] was significantly higher than that with other infections. The number of comet-tail sign in patients with ARDS was significantly higher than that in patients without ARDS [27 (19, 30) vs. 15 (9, 24), H = 25.387, P < 0.001]. Multivariate Logistic regression analysis showed that EVLWI, the number of comet-tail signs and PVPI were independent risk factors for death in septic patients [odds ratio (OR) and 95% confidence interval (95%CI) were 10.772 (1.161-99.851), 2.360 (1.070-5.202), 2.042 (1.152-3.622), all P < 0.05]. The accuracy, sensitivity, specificity, positive predictive value, negative predictive value of Logistic regression model based on comet-tail sign and EVLWI were 90.0%, 90.0%, 90.0%, 81.8%, 94.7%, respectively, and area under curve (AUC) were 0.926±0.018, 95%CI was 0.912-0.975, P < 0.001. CONCLUSIONS: The transthoracic lung ultrasound comet-tail in septic patients is significantly correlated with EVLWI monitored by PiCCO. The transthoracic lung ultrasound comet-tail combined with EVLWI can better improve the sensitivity, specificity and accuracy of 28-day prognosis in septic patients.

The Association Between the Tumor Necrosis Factor-Alpha Gene -308A/G Polymorphism and Chronic Pancreatitis: A Meta-Analysis.

Background: Tumor necrosis factor-alpha (TNF-α) is a major proinflammatory cytokine that has been posited to be involved in the development of chronic pancreatitis (CP). Several studies have been carried out that explored the association between the TNF-α -308A/G polymorphism and CP; however, conflicting results have emerged. The aim of this study was to perform a meta-analysis to provide a more precise assessment of the relationship between the TNF-α -308A/G polymorphism and CP risk. Methods: Case-control studies were identified using PubMed, Embase, Web of Science, Cochrane Library, and Chinese National Knowledge Infrastructure through January 2019 from which seven were identified that met all inclusion criteria. Results: This meta-analysis included 695 CP cases and 742 controls. A positive association was found between the A allele and the risk of CP using the additive model (OR [odds ratio] = 1.83, 95% CI [confidence interval] = 1.08-3.10). We also found, after excluding the Hardy-Weinberg equilibrium-violating studies, that the AA genotype was significantly associated with CP in both the additive and recessive models (OR = 2.28, 95% CI = 1.27-4.07; OR = 2.19, 95% CI = 1.26-3.81). Conclusion: This meta-analysis indicates that the A allele of the TNF-α -308A/G polymorphism increases the risk of CP.

[Gelsolin level for prognostic evaluation in patients with critically illness].

OBJECTIVE: To investigate the changes of plasma gelsolin level in patients with critical illness and its application in prognostic evaluation. METHODS: Ninety six critically ill patients admitted in ICU of Sichuan Provincial People's Hospital from February 2012 to December 2013 were enrolled in the prospective cohort study. Plasma gelsolin levels were detected with enzyme linked immunosorbent assay (ELISA) at admission (d1), d2, d4 and d8 after admission, and also detected in blood samples of 186 healthy subjects as controls. Logistic regression model was used to analyze the relationship between the level of plasma gelsolin and prognosis of patients. RESULTS: The average levels of plasma gelsolin were significantly lower in critically ill patients than those in control subjects (F=1986.37, P<0.01). There was significant difference in overall level of gelsolin between survival patients and fatal patients (F=16.691, P<0.01). APACHE Ⅱ score was associated with survival outcomes (r=0.489, P=0.009); the APACHE Ⅱ score was significantly higher in fatal patients than that in survival patients (29.5±7.7 vs 22.1±5.7, t=5.375, P<0.01). There was a negative correlation between plasma gelsolin levels and fatal outcomes (r=-0.512, P<0.01). Logistic regression analysis showed that the overall plasma gelsolin levels and the last measured level was a prognostic factor for critically ill patients (P<0.05). CONCLUSION: Plasma gelsolin levels are correlated with the severity of critically ill patients, and plasma gelsolin can be used as indicator of prognosis.

G771C Polymorphism in the MLXIPL Gene Is Associated with a Risk of Coronary Artery Disease in the Chinese: A Case-Control Study.

OBJECTIVES: Previously, a genome-wide scan has identified a nonsynonymous single nucleotide polymorphism (rs3812316, G771C, Gln241His) in the MLXIPL gene that is associated with the level of plasma triglycerides. However, no data are available on the association of this polymorphism with coronary artery disease (CAD) in the Chinese population. The aim of this study was to evaluate the association between a gene polymorphism related to triglyceride metabolism and CAD. METHODS: The genotype of the polymorphism in the MLXIPL gene was determined in 352 CAD patients and 152 CAD-free subjects. All of the participants were selected to study the MLXIPL gene rs3812316 polymorphism using the polymerase chain reaction restriction fragment length polymorphism method. RESULTS: In Chinese participants, we observed that there was a significant difference in genotype between the cases and controls (p = 0.002). After allowance for potential confounders, unconditional logistic analysis revealed that the SNP was significantly related to a risk in CAD patients (adjusted OR 2.96, 95% CI 1.30-5.08; p =0.004). We also found that there was a significant association between the single nucleotide polymorphism and plasma triglyceride levels (OR 1.28, 95% CI 1.061-1.542; p < 0.05). CONCLUSION: The gene sequence variation in the MLXIPL gene may serve as a novel genetic marker for the risk of significant CAD.