Predictive value of free triiodothyronine to free thyroxine ratio on contrast-associated acute kidney injury and poor prognosis in euthyroid patients after percutaneous coronary intervention.

PURPOSE: The purpose of the study was to explore the predictive value of free triiodothyronine to free thyroxine ratio (FT3/FT4) on contrast-associated acute kidney injury (CA-AKI) and poor prognosis in euthyroid patients after percutaneous coronary intervention (PCI). METHODS: The present study included 3,116 euthyroid patients who underwent elective PCI. The main outcome was CA-AKI, and the secondary outcome was long-term mortality. All patients were divided into three groups according to the tertiles of FT3/FT4 levels. RESULTS: During hospitalization, a total of 160 cases (5.1%) of CA-AKI occurred. Restricted cubic spline (RCS) analysis indicated a linear and negative relationship between FT3/FT4 and CA-AKI risk (P for nonlinearity = 0.2621). Besides, the fully-adjusted logistic regression model revealed that patients in tertile 3 (low FT3/FT4 group) had 1.82 times [odds ratio (OR): 1.82, 95% confidence interval (CI): 1.13-3.02, P = 0.016] as high as the risk of CA-AKI than those in tertile 1 (high FT3/FT4 group). Similarly, patients in tertile 3 were observed to have a higher incidence of long-term mortality [fully-adjusted hazard ratio (HR): 1.58, 95% CI: 1.07-2.32, P = 0.021]. Similarly, the Kaplan-Meier curves displayed significant differences in long-term mortality among the three groups (log-rank test, P < 0.001). CONCLUSION: In euthyroid patients undergoing elective PCI, low levels of FT3/FT4 were independently associated with an increased risk of CA-AKI and long-term mortality. Routine evaluation of FT3/FT4 may aid in risk stratification and guide treatment decisions within this particular patient group.

The Association of Intraindividual Difference Between Cystatin- and Creatinine-Based Estimated GFR and Contrast-Associated Acute Kidney Injury.

Purpose: The estimated glomerular filtration rate (eGFR) based on creatinine is crucial for the risk assessment of contrast-associated acute kidney injury (CA-AKI). In recent, the difference between cystatin C-based eGFR (eGFRcys) and creatinine-based eGFR (eGFRcr) has been widely documented. We aimed to explore whether intraindividual differences between eGFRcys and eGFRcr had potential value for CA-AKI risk assessment in patients undergoing elective percutaneous coronary intervention (PCI). Patients and Methods: From January 2012 to December 2018, we retrospectively observed 5049 patients receiving elective PCI. To determine eGFR, serum creatinine and cystatin C levels were measured. CA-AKI was defined as serum creatinine being increased ≥ 50% or 0.3 mg/dL within 48 h after contrast agents exposure. Chronic kidney disease (CKD) was defined as the eGFR < 60 mL/min/1.73 m2. Results: Approximately half of the participants (2479, 49.1%) had a baseline eGFRdiff (eGFRcys-eGFRcr) between -15 and 15 mL/min/1.73 m2. Restricted cubic splines analysis revealed a nonlinear relationship between eGFRdiff and CA-AKI. Multivariable logistic regression analysis indicated that compared with the reference group (-15 to 15 mL/min/1.73 m2), the negative-eGFRdiff group (less than -15 mL/min/1.73 m2) had a higher risk of CA-AKI (OR, 3.44; 95% CI, 2.57-4.64). Furthermore, patients were divided into four groups based on CKD identified by eGFRcys or eGFRcr. Multivariable logistic analysis revealed that patients with either CKDcys (OR, 2.94; 95% CI, 2.19-3.95, P < 0.001) or CKDcr (OR, 2.44; 95% CI, 1.19-4.63, P < 0.001) had an elevated risk of CA-AKI compared to those without CKDcys and CKDcr. Conclusion: There are frequent intraindividual differences between eGFRcys and eGFRcr, and these differences can be used to forecast the risk of CA-AKI.

Lactate dehydrogenase-to-albumin ratio: A superior inflammatory marker for predicting contrast-associated acute kidney injury after percutaneous coronary intervention.

PURPOSE: Inflammation is commonly considered a mechanism underlying contrast-associated acute kidney injury (CA-AKI). This study aimed to explore the predictive capability of the novel inflammatory marker lactate dehydrogenase-to-albumin ratio (LAR) for CA-AKI following percutaneous coronary intervention (PCI), and further compare it with other common inflammatory biomarkers. METHODS: This study enrolled 5,435 patients undergoing elective PCI. The primary outcome was CA-AKI, and the secondary outcome was all-cause mortality. All patients were grouped into three groups based on the LAR tertiles. RESULTS: Three hundred fifteen patients (5.8%) experienced CA-AKI during hospitalization. The fully adjusted logistic regression suggested a significant increase in the risk of CA-AKI in LAR Tertile 3 (odds ratio [OR]: 2.51, 95% confidence interval [CI]: 1.68-3.83, p < .001) and Tertile 2 (OR: 2.11, 95% CI: 1.42-3.20, p < .001) compared to Tertile 1. Additionally, receiver operating characteristic (ROC) analysis demonstrated that LAR exhibited significantly superior predictive capability for CA-AKI compared to other inflammatory biomarkers. Regarding the secondary outcome, multivariate COX regression analysis showed a positive correlation between elevated LAR levels and all-cause mortality. CONCLUSION: In patients undergoing elective PCI, LAR was significantly independently associated with CA-AKI, and it stood out as the optimal inflammatory biomarker for predicting CA-AKI.

The Prognostic Value of the Age-D-Dimer-Albumin Score in Patients with Acute Myocardial Infarction Undergoing Percutaneous Coronary Intervention.

BACKGROUND: The Age-D-dimer-Albumin (ADA), the CREDO-Kyoto, and the PARIS scores have been established to predict thrombotic events. However, the prognostic performance of these scores compared to the GRACE score in patients with acute myocardial infarction (AMI) undergoing percutaneous coronary intervention (PCI) has not been reported. METHODS: Consecutive AMI patients treated with PCI were retrospectively enrolled at a teaching hospital in China from January 2016 to December 2019. The primary endpoint was all-cause mortality and the secondary endpoint was cardiac death. Harrell's C-index and net reclassification improvement (NRI) were used to compare the prognostic value of these scores with the GRACE score for mortality. RESULTS: Of the 1,578 patients enrolled, the mean age was 62.5 years, and 23.5% were female. During a median follow-up of 3.8 years, 146 all-cause deaths and 80 cardiac deaths occurred. The ADA score showed a better prognostic performance than the GRACE (Harrell's C-index: 0.800 vs. 0.749; p = 0.003), the CREDO-Kyoto (Harrell's C-index: 0.800 vs. 0.765; NRI = 0.348, p < 0.001), and the PARIS scores (Harrell's C-index: 0.800 vs. 0.694; NRI = 0.556, p < 0.001). In the multivariable Cox regression analysis, the ADA score was independently associated with all-cause mortality (hazard ratio [HR] = 1.641 per 10-point increment, 95% confidence interval [CI]: 1.397-1.929) and cardiac death (HR = 1.636 per 10-point increment, 95% CI: 1.325-2.020). The risk of all-cause mortality and cardiac death increased with the rising of the ADA score. CONCLUSION: The ADA score showed a better prognostic performance than the GRACE, the CREDO-Kyoto, and the PARIS scores in patients with AMI undergoing PCI, which was a potential predictive tool for mortality.

Lactiplantibacillus plantarum GL001 alleviates jejunal oxidative damage induced by intestinal ischemia-reperfusion injury by influencing jejunal tissue metabolism through the improvement of jejunal microbial composition.

Intestinal ischemia-reperfusion (IIR) injury is associated with inflammation and oxidative stress, yet its precise mechanisms remain not fully understood. IIR injury is closely linked to the gut microbiota and its metabolites. The anti-inflammatory and antioxidant effects of Lactiplantibacillus plantarum are specific to IIR. In our study, we conducted a 30-day pre-treatment of SD rats with both a standard strain of Lactiplantibacillus plantarum and Lactiplantibacillus plantarum GL001. After a 7-day cessation of treatment, we induced an IIR injury model to investigate the mechanisms by which Lactiplantibacillus plantarum alleviates IIR damage. The results demonstrate that Lactiplantibacillus plantarum effectively mitigates the inflammatory and oxidative stress damage induced by IIR. Lactiplantibacillus plantarum GL001 can improve the gut microbiota by reducing the abundance of harmful bacteria and increasing the abundance of beneficial bacteria. In IIR intestinal tissue, the levels of secondary bile acids are elevated. The content of the bacterial metabolite Calcimycin increases. Annotations of metabolic pathways suggest that Lactiplantibacillus plantarum GL001 can alleviate IIR damage by modulating calcium-phosphorus homeostasis through the regulation of parathyroid hormone synthesis, secretion, and action. Microbiota-metabolite correlation analysis reveals a significant negative correlation between calcimycin and Lactonacillus and a significant positive correlation between calcimycin and Shigella. There is also a significant positive correlation between calcimycin and secondary bile acids. Lactiplantibacillus plantarum GL001 can alleviate oxidative damage induced by IIR through improvements in gut microbiota and intestinal tissue metabolism.

Risk factors of pulmonary arterial hypertension in patients with systemic lupus erythematosus: A meta-analysis.

OBJECTIVE: To determine the risk factors of pulmonary arterial hypertension (PAH) related to systemic lupus erythematosus (SLE) through systematic reviews and meta-analyses. METHODS: We undertook electronic search strategies using Medline via PubMed, Embase, Web of Science, and Cochrane Library up to April 11, 2023. Study selection and data extraction were performed by 2 authors independently. We made risk of bias judgments based on the Newcastle-Ottawa Scale (NOS). Pooled risk ratios (RRs) and 95% confidence intervals (CIs) were calculated to estimate the overall effect sizes of potential risk factors for PAH in SLE patients. Univariate and multivariate meta-regression models were used to assess the independent effects of each risk factor on PAH. Sensitivity analyses were also conducted to explore potential sources of heterogeneity. RESULTS: A total of 19 articles were included in this meta-analysis, and the results showed that gender (female) [RR = 1.04, 95% CI (1.02, 1.06), p = .0001], interstitial lung disease [RR = 4.36, 95% CI (2.42, 7.85), p = .0001], alopecia [RR = 1.39, 95% CI (1.06, 1.83), p = .017], Raynaud's phenomenon [RR = 1.83, 95% CI (1.41, 2.37), p = .0001], systemic hypertension [RR = 1.30, 95% CI (1.07, 1.58), p = .007], serositis [RR = 2.29, 95% CI (1.89, 2.77), p = .0001], pericardial effusion [RR = 3.33, 95% CI (2.20, 5.05), p = .0001], anti-RNP [RR = 1.86, 95% CI (1.19, 2.91), p = .006], anti-SSA [RR = 1.28, 95% CI (1.01, 1.62), p = .041], anti-SSB [RR = 1.38, 95% CI (1.19, 1.60), p = .0001], anti-U1RNP [RR = 1.58, 95% CI (1.07, 2.34), p = .023], thrombocytopenia [RR = 1.38, 95% CI (1.14, 1.68), p = .001], and current smokers [RR = 2.20, 95% CI (1.19, 4.06), p = .012] were all risk factors for PAH related to SLE. CONCLUSION: PAH is a serious complication of SLE. Since prognosis of SLE patients after the occurrence of PAH is poor, routine examination should be conducted for SLE patients with PAH risk factors.

Predictive Value of Systemic Inflammation Score for Contrast-Associated Acute Kidney Injury and Adverse Outcomes Among Patients Undergoing Elective Percutaneous Coronary Intervention.

Purpose: Prior research has demonstrated a key role of systemic inflammatory state in the pathogenesis and progression of contrast-associated acute kidney injury (CA-AKI). Recently, the systemic inflammation score (SIS) has been introduced to evaluate the inflammatory status, utilizing the lymphocyte-to-monocyte ratio (LMR) and albumin. The primary objective of this study was to determine whether the SIS can predict CA-AKI and long-term prognosis in patients undergoing elective percutaneous coronary intervention (PCI). Patients and Methods: A total of 5726 patients who underwent elective PCI were included from January 2012 to December 2018. The primary outcome was CA-AKI, defined as an increase in serum creatinine (SCr) ≥0.3 mg/dl or ≥50% than baseline SCr within 48 h after the PCI procedure. The secondary outcome was long-term mortality. All patients were classified into low- and high-SIS groups. Results: During hospitalization, 349 (6.1%) patients developed CA-AKI. Multivariate logistic regression analysis showed that patients in the high SIS group had a 1.47-fold higher risk of developing CA-AKI than those in the low SIS group [odds ratio (OR): 1.50, 95% confidence interval (CI): 1.12-2.01, P =0.006]. Furthermore, the SIS showed the greatest prediction performance for CA-AKI compared with other inflammatory hematological ratios. In the multivariate Cox regression analysis, the high SIS group was found to be closely associated with long-term mortality [hazard ratio (HR): 1.58, 95% CI: 1.26-1.97, P <0.001, vs low SIS group]. The Kaplan-Meier curve analysis also demonstrated a difference in long-term mortality between the two groups (Log rank test, P <0.001). Conclusion: The SIS was closely associated with CA-AKI and long-term mortality in patients after elective PCI. Thus, more attention should be paid to exploring the potential benefits of anti-inflammatory strategies in preventing CA-AKI and improving the prognosis of patients undergoing PCI.

Accuracy and capability of tri-ponderal mass index in assessing cardio-metabolic risk factors in Chinese children and adolescents aged 3 to 17 years, compared with body mass index.

BACKGROUND: Tri-ponderal mass index (TMI) has been reported to be a more accurate estimate of body fat than body mass index (BMI). This study aims to compare the effectiveness of TMI and BMI in identifying hypertension, dyslipidemia, impaired fasting glucose (IFG), abdominal obesity, and clustered cardio-metabolic risk factors (CMRFs) in 3- to 17-year-old children. METHODS: A total of 1587 children aged 3 to 17 years were included. Logistic regression was used to evaluate correlations between BMI and TMI. Area under the curves (AUCs) were used to compare discriminative capability among indicators. BMI was converted to BMI- z scores, and accuracy was compared by false-positive rate, false-negative rate, and total misclassification rate. RESULTS: Among children aged 3 to 17 years, the mean TMI was 13.57 ±â€Š2.50 kg/m 3 for boys and 13.3 ±â€Š2.33 kg/m 3 for girls. Odds ratios (ORs) of TMI for hypertension, dyslipidemia, abdominal obesity, and clustered CMRFs ranged from 1.13 to 3.15, higher than BMI, whose ORs ranged from 1.08 to 2.98. AUCs showed similar ability of TMI (AUC: 0.83) and BMI (AUC: 0.85) in identifying clustered CMRFs. For abdominal obesity and hypertension, the AUC of TMI was 0.92 and 0.64, respectively, which was significantly better than that of BMI, 0.85 and 0.61. AUCs of TMI for dyslipidemia and IFG were 0.58 and 0.49. When 85th and 95th of TMI were set as thresholds, total misclassification rates of TMI for clustered CMRFs ranged from 6.5% to 16.4%, which was not significantly different from that of BMI- z scores standardized according to World Health Organization criteria. CONCLUSIONS: TMI was found to have equal or even better effectiveness in comparison with BMI in identifying hypertension, abdominal obesity, and clustered CMRFs TMI was more stable than BMI in 3- to 17-year-old children, while it failed to identify dyslipidemia and IFG. It is worth considering the use of TMI for screening CMRFs in children and adolescents.

Shrunken Pore Syndrome: A New and More Powerful Phenotype of Renal Dysfunction Than Chronic Kidney Disease for Predicting Contrast-Associated Acute Kidney Injury.

Background Shrunken pore syndrome (SPS) as a novel phenotype of renal dysfunction is characterized by a difference in renal filtration between cystatin C and creatinine. The manifestation of SPS was defined as a cystatin C-based estimated glomerular filtration rate (eGFR) <60% of the creatinine-based eGFR. SPS has been shown to be associated with the progression and adverse prognosis of various cardiovascular and renal diseases. However, the predictive value of SPS for contrast-associated acute kidney injury (CA-AKI) and long-term outcomes in patients undergoing percutaneous coronary intervention remains unclear. Methods and Results We retrospectively observed 5050 consenting patients from January 2012 to December 2018. Serum cystatin C and creatinine were measured and applied to corresponding 2012 and 2021 Chronic Kidney Disease Epidemiology Collaboration equations, respectively, to calculate the eGFR. Chronic kidney disease (CKD) was defined as a creatinine-based eGFR <60 mL/min per 1.73 m2 without dialysis. CA-AKI was defined as an increase in serum creatinine ≥50% or 0.3 mg/dL within 48 hours after contrast medium exposure. Overall, 649 (12.85%) patients had SPS, and 324 (6.42%) patients developed CA-AKI. Multivariate logistic regression analysis indicated that SPS was significantly associated with CA-AKI after adjusting for potential confounding factors (odds ratio [OR], 4.17 [95% CI, 3.17-5.46]; P<0.001). Receiver operating characteristic analysis indicated that the cystatin C-based eGFR:creatinine-based eGFR ratio had a better performance and stronger predictive power for CA-AKI than creatinine-based eGFR (area under the curve: 0.707 versus 0.562; P<0.001). Multivariate logistic analysis revealed that compared with those without CKD and SPS simultaneously, patients with CKD and non-SPS (OR, 1.70 [95% CI, 1.11-2.55]; P=0.012), non-CKD and SPS (OR, 4.02 [95% CI, 2.98-5.39]; P<0.001), and CKD and SPS (OR, 8.62 [95% CI, 4.67-15.7]; P<0.001) had an increased risk of CA-AKI. Patients with both SPS and CKD presented the highest risk of long-term mortality compared with those without both (hazard ratio, 2.30 [95% CI, 1.38-3.86]; P=0.002). Conclusions SPS is a new and more powerful phenotype of renal dysfunction for predicting CA-AKI than CKD and will bring new insights for an accurate clinical assessment of the risk of CA-AKI.

[Research progress on liposome and nanomicelle targeted drug delivery system across blood-brain barrier].

The blood-brain barrier(BBB), a protective barrier between brain tissues and brain capillaries, can prevent drugs from entering the brain tissues to exert the effect, which greatly increases the difficulty in treating brain diseases. The drug delivery system across the BBB can allow efficient drug delivery across the BBB by virtue of carriers and formulations, thereby enhancing the therapeutic effect of drugs on brain tissue diseases. Liposomes and micelles have been extensively studied with advances in the targeted therapy across the BBB for the brain due to their unique structures and drug delivery advantages. This study summarized the research status of liposome and micelle drug delivery systems across the BBB based on the literature in recent years and analyzed their application advantages and mechanism in terms of trans-BBB capability, targeting, and safety. Moreover, the problems and possible countermeasures in the research on trans-BBB liposomes and micelles were discussed according to the current clinical translation, which may provide refe-rences and ideas for the development of trans-BBB targeted nano-drugs.

Weight-to-height ratio and body roundness index are superior indicators to assess cardio-metabolic risks in Chinese children and adolescents: compared with body mass index and a body shape index.

Objective: To assess the relationship between five anthropometric indicators, which includes body mass index (BMI), weight-to-height ratio (WHtR), a body shape index (ABSI), ABSI-adolescents, and body roundness index (BRI) in Chinese children and adolescents, and select which could better predict cardio-metabolic risk factors (CMRFs). Methods: Cross-sectional study with 1,587 participants aged 3 to 17 years. Five anthropometric indicators were calculated according to weight, height and waist circumference (WC). Anthropometric measurements and laboratory indicators were used to diagnose CMRFs, which included hypertension, dyslipidemia, impaired fasting glucose and abdominal obesity. Partial correlation analysis was used to evaluate the relationship among anthropometric indicators, area under the receiver operating characteristic curve (AUCs) were used to compare the predict ability of each anthropometric indicators, the cut-off value, sensitivity, specificity and Youden Index of each indicator were calculated. Results: In 3-6 years old children, ABSI-adolescent positively correlated with WC (r=0.727, P<0.001), BMI (r=0.218, P<0.001) and WHtR (r=0.752, P<0.001), and in 7-17 years old participants, the correlation coefficients increased to 0.842, 0.563 and 0.850 (P<0.001), respectively. BRI were strong correlated with BMI, WHtR and ABSI-adolescents in both age group (P<0.001). In 3-6 years group, the ROC analysis showed that BMI and ABSI were significantly better in identifying hypertension in both genders, WHtR and BRI were significantly better in identifying abdominal obesity in girls, but all of them were failed in identifying dyslipidemia and hyperglycemia. In 7-17 years group, WHtR and BRI were significantly better in identifying hypertension, dyslipidemia, abdominal obesity in both genders, BMI and ABSI performed better in identifying hyperglycemia in girls. Conclusions: In Chinese children aged 3-6 years, there is no indicator performed best in all the CMRFs, in 7-17 years old teenagers, WHtR and BRI can be recommended to identify hypertension, dyslipidemia, abdominal obesity and clustered CMRFs in both genders. However, ABSI showed weak discriminative power.

Efficacy and tolerability of lamotrigine in the treatment of focal epilepsy among children and adolescents: a meta-analysis.

BACKGROUND: Epilepsy is the most common chronic neurological disease in children, and focal epileptic seizures are the most common subtype. Unlike the data supporting treatment options for adults with epilepsy, evidence regarding the most effective first-line drug therapy for focal epilepsy in children and adolescents is limited. While lamotrigine is a therapeutic option for adults, there are disagreements surrounding its efficacy and tolerability in the younger population. Therefore, we performed a meta-analysis to determine if there was sufficient evidence to support a more definitive recommendation. METHODS: We undertook electronic search strategies using Medline via Ovid SP, Embase via Ovid SP up to February 05, 2021. We also searched relevant articles through Chinese BioMedical Literature (CBM), Chinese National Knowledge Infrastructure (CNKI), WANFANG, and VIP databases up to February 05, 2021. Study selection and data extraction were performed by 2 authors independently. The randomized controlled trials on focal epilepsy in children were included, and we made risk of bias judgments based on the methods endorsed by The Cochrane Collaboration. We used fifty percent or greater reduction in seizure frequency as an indicator of efficacy, the incidence of adverse events and treatment withdrawal as indicators of tolerability. The strength of the correlation was assessed via risk ratios (RRs) and their 95% confidence intervals (95% CIs). RESULTS: A total of 7 randomized trials involving 757 participants fulfilled the eligibility criteria. Of the 7 trials, 3 were placebo-controlled, and 4 compared lamotrigine with carbamazepine or oxcarbazepine. Lamotrigine was significantly more effective than placebo in achieving ≥50% reduction in seizure frequency, but its efficacy was not significantly different from that of carbamazepine or oxcarbazepine (lamotrigine vs. placebo: RR 2.95, 95% CI, 1.88 to 4.61; lamotrigine vs. carbamazepine/oxcarbazepine: RR 0.95, 95% CI, 0.85 to 1.05. There was significant difference in the incidence of overall adverse events between the lamotrigine- and carbamazepine/oxcarbazepine-treated groups (RR 0.64, 95% CI, 0.45 to 0.90). CONCLUSIONS: Lamotrigine was effective in reducing the seizure frequency when used as an add-on treatment in children with focal epilepsy, but current evidence does not suggest that lamotrigine is superior to carbamazepine/oxcarbazepine as monotherapy. For overall adverse events, lamotrigine has significantly fewer than carbamazepine/oxcarbazepine, suggesting that lamotrigine has better tolerability.

[A novel bifunctional in vivo mutation detection system].

A shuttle plasmid pMCLacI/neo with two copies of LacI was integrated into mouse genome and a novel system which could detect in vivo mutation of both expression and silence genes was constructed, enabling the comparative analysis of their mutation spectra and mutant frequencies. 486 fertilized eggs from C57BL/6 mice with microinjected pMCLacI/neo plasmid were transferred into oviducts of 18 pseudo-pregnant mice, and 32 alive offsprings were screened and identified by using PCR and Southern blotting. Genomes of 5 mice had pMCLacI/neo plasmid integrated, as verified by Southern blot after the PCR screening. Only one of the two LacI in pMCLacI/neo was in expression state; and this established a model, that the status in vivo of both gene expression and silencing could be simulated. This kind of mice might be used as a novel bifunctional mutation detection system in vivo.