Association between the American Heart Association's new "Life's Essential 8" metrics and kidney stone.

PURPOSE: The incidence of kidney stone disease has increased worldwide, resulting in high medical costs and social burden. Kidney stone disease shares some common features with the risk factors of cardiovascular diseases (CVDs). We investigated the association between cardiovascular health (CVH) based on the Life's Essential 8 (LE8) score developed by the American Heart Association and the incidence of kidney stone disease. METHODS: We analyzed the data of 29,469 US adults aged 20 years or above from the National Health and Nutrition Examination Survey, 2007-2018. According to the LE8 score, CVH was divided into three categories: poor, intermediate, and ideal. Logistic regression was used to determine the association between CVH and the incidence of kidney stone disease by estimating odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: The average age of the participants was 48.6 years, and 50% of the participants were women. The numbers of participants with poor, intermediate, and ideal CVH were 4149, 19,782, and 5538, respectively. After adjusting for related confounding factors, ideal CVH was associated with a reduction in the odds of kidney stone occurrence as compared to poor CVH (adjusted OR [aOR]: 0.45, 95% CI: 0.35-0.57, p < 0.001). Moreover, if the ideal CVH metrics was ≥ 6, the odds of kidney stone occurrence decreased by up to 61% (aOR: 0.39, 95% CI: 0.30-0.51). CONCLUSIONS: In the present study, ideal CVH, a factor indicative of a healthy lifestyle, was associated with lower odds of kidney stone occurrence.

Prognostic value of triglyceride glucose index in population at high cardiovascular disease risk.

BACKGROUND: Early identification of populations at high cardiovascular disease (CVD) risk and improvement of risk factors can significantly decrease the probability of CVD development and improve outcomes. Insulin resistance (IR) is a CVD risk factor. The triglyceride glucose (TyG) index is a simple and reliable index for evaluating IR. However, no clinical studies on the prognostic value of the TyG index in a high risk CVD population have been conducted. This study evaluated the relationship between the TyG index and prognosis in a high risk CVD population. METHODS: This study enrolled 35,455 participants aged 35-75 years who were at high CVD risk and visited selected health centers and community service centers between 2017 and 2021. Their general clinical characteristics and baseline blood biochemical indicators were recorded. The TyG index was calculated as ln[fasting triglyceride (mg/dl)× fasting blood glucose (mg/dl)/2]. The endpoints were all-cause death and cardiovascular death during follow-up. Cox proportional hazard models and restricted cubic spline (RCS) analysis were used to evaluate the correlation between the TyG index and endpoints. RESULTS: In the overall study population, the mean age of all participants was 57.9 ± 9.6 years, 40.7% were male, and the mean TyG index was 8.9 ± 0.6. All participants were divided into two groups based on the results of the RCS analysis, with a cut-off value of 9.83. There were 551 all-cause deaths and 180 cardiovascular deaths during a median follow-up time of 3.4 years. In the multivariate Cox proportional hazard model, participants with a TyG index ≥ 9.83 had a higher risk of all-cause death (Hazard ratio [HR] 1.86, 95% Confdence intervals [CI] 1.37-2.51, P<0.001) and cardiovascular death (HR 2.41, 95%CI 1.47-3.96, P = 0.001) than those with a TyG index < 9.83. Subgroup analysis revealed that there was no interaction between the TyG index and variables in all subgroup analyses. CONCLUSIONS: The high TyG index was associated with an increased risk of all-cause death and cardiovascular death in people at high risk of CVD. This finding demonstrates the value of the TyG index in the primary prevention of CVD. TRIAL REGISTRATION: retrospectively registered, the registration number is K2022-01-005 and the date is 2022.01.30.

Elevated urine albumin creatinine ratio increases cardiovascular mortality in coronary artery disease patients with or without type 2 diabetes mellitus: a multicenter retrospective study.

BACKGROUND: Albuminuria has been suggested as an atherosclerotic risk factor among the general population. However, whether this association will be amplified in patients with coronary artery disease (CAD) is unknown. It is also unknown whether diabetes mellitus confounds the association. We aim to analyse the prognosis of elevated urine albumin creatinine ratio (uACR) in the CAD population with or without type 2 diabetes mellitus (T2DM). METHODS: This multi-center registry cohort study included 5,960 patients with CAD. Patients were divided into T2DM and non-T2DM group, and baseline uACR levels were assessed on three grades (low: uACR < 10 mg/g, middle: 10 mg/g ≤ uACR < 30 mg/g, and high: uACR ≥ 30 mg/g). The study endpoints were cardiovascular mortality and all-cause mortality. RESULTS: During the median follow-up of 2.2 [1.2-3.1] years, 310 (5.2%) patients died, of which 236 (4.0%) patients died of cardiovascular disease. CAD patients with elevated uACR had a higher risk of cardiovascular mortality (middle: HR, 2.32; high: HR, 3.22) than those with low uACR, as well as all-cause mortality. Elevated uACR increased nearly 1.5-fold risk of cardiovascular mortality (middle: HR, 2.33; high: HR, 2.34) among patients without T2DM, and increased 1.5- fold to 3- fold risk of cardiovascular mortality in T2DM patients (middle: HR, 2.49; high: HR, 3.98). CONCLUSIONS: Even mildly increased uACR could increase the risk of cardiovascular mortality in patients with CAD, especially when combined with T2DM.

Independent effects of the triglyceride-glucose index on all-cause mortality in critically ill patients with coronary heart disease: analysis of the MIMIC-III database.

BACKGROUND: The triglyceride-glucose (TyG) index is a reliable alternative biomarker of insulin resistance (IR). However, whether the TyG index has prognostic value in critically ill patients with coronary heart disease (CHD) remains unclear. METHODS: Participants from the Medical Information Mart for Intensive Care III (MIMIC-III) were grouped into quartiles according to the TyG index. The primary outcome was in-hospital all-cause mortality. Cox proportional hazards models were constructed to examine the association between TyG index and all-cause mortality in critically ill patients with CHD. A restricted cubic splines model was used to examine the associations between the TyG index and outcomes. RESULTS: A total of 1,618 patients (65.14% men) were included. The hospital mortality and intensive care unit (ICU) mortality rate were 9.64% and 7.60%, respectively. Multivariable Cox proportional hazards analyses indicated that the TyG index was independently associated with an elevated risk of hospital mortality (HR, 1.71 [95% CI 1.25-2.33] P = 0.001) and ICU mortality (HR, 1.50 [95% CI 1.07-2.10] P = 0.019). The restricted cubic splines regression model revealed that the risk of hospital mortality and ICU mortality increased linearly with increasing TyG index (P for non-linearity = 0.467 and P for non-linearity = 0.764). CONCLUSIONS: The TyG index was a strong independent predictor of greater mortality in critically ill patients with CHD. Larger prospective studies are required to confirm these findings.

The predictive value of the neutrophil/platelet ratio on in-hospital adverse events and long-term prognosis in patients with coronary artery disease after percutaneous coronary intervention and its possible internal mechanism.

The neutrophil-to-platelet ratio (NPR) is considered to be an indicator of inflammatory status. The value of the NPR in predicting in-hospital adverse events (AEs) and long-term prognosis after percutaneous coronary intervention (PCI) in coronary artery disease (CAD) patients has not yet been reported. Meanwhile, the mechanisms behind its predictive value for long-term prognosis remain unreported as well. The study retrospectively enrolled 7284 consecutive patients with CAD undergoing PCI from January 2012 to December 2018. Multivariable logistic regression analysis, multivariable Cox regression analysis, Kaplan‒Meier (KM) curve analysis, restricted cubic spline (RCS) curve analysis, and sensitivity analysis were used in the study. All-cause death was the endpoint of the study. According to the median value of the NPR, the patients were divided into two groups: the high group (NPR ≥ 0.02, n = 3736) and the low group (NPR < 0.02, n = 3548). Multivariate logistic regression analysis demonstrated that a high NPR was a risk factor for in-hospital AEs [odds ratio (OR) = 1.602, 95% CI 1.347-1.909, p = 0.001]. During a mean follow-up period of 3.01 ± 1.49 years, the multivariate Cox regression analysis showed that a high NPR affected the long-term prognosis of patients (HR 1.22, 95% CI 1.03-1.45, p = 0.025) and cardiac death (HR 1.49, 95% CI 1.14-1.95, p = 0.003). The subgroup analysis showed that the NPR was affected by age and sex. The mediation analysis identified that the effect of the NPR on long-term outcomes is partially mediated by serum creatinine (Scr) and triglycerides. The NPR may be a convenient indicator of in-hospital AEs and poor long-term and cardiac outcomes in CAD patients. It might have impacted prognosis through effects on kidney function and lipid metabolism.

Influence of renal function on the ability of TyG Index to predict all-cause mortality.

BACKGROUND: The association between triglyceride-glucose (TyG) index and poor prognosis remains controversial. Whether renal function status affects the ability of the TyG index to predict poor prognosis has not yet been elucidated and merits further studies. METHODS: This retrospective cohort study included 22,031 participants from communities in the U.S. By juxtaposing the TyG categories with the estimated glomerular filtration rate (eGFR, either < 60 mL/min/1.73m2 or ≥ 60 mL/min/1.73m2), participants were categorized into four distinct groups: (1) TyG_L/eGFR_H; (2) TyG_H/eGFR_H; (3) TyG_L/eGFR_L; and (4) TyG_H/eGFR_L. The endpoint was the all-cause mortality rate. Standard Kaplan-Meier plots were constructed and multifactor Cox regression analyses were carried out and restricted cubic spline regression analysis was utilized to assess the association between death and the TyG index for different renal function statuses. RESULTS: No statistical differences were found in the TyG groups in participants with normal renal function after adjustment for all covariates (P = 0.070). However, in the high TyG index group with renal insufficiency, the risk of all-cause mortality rates was reduced by 18%. (HR, 0.82; CI, 0.69-0.98). The TyG index (high vs. low) and renal function (eGFR < 60 vs. eGFR ≥ 60) had statistically significant interactions with death (P < 0.001). When all covariates were adjusted, the risk of mortality for the TyG_L combined with eGFR_L group was 56% higher than that for the TyG_L combined with eGFR_H group (HR, 1.56; CI, 1.33-1.82). In the renal insufficiency population, a nonlinear relationship was observed between mortality and the TyG index, albeit with a differing pattern (P for nonlinearity < 0.001). CONCLUSIONS: While it has been known that TyG index was a prognosis marker of CVD, this research highlights that higher TyG index was associated with higher all-cause mortality rates for all participants. Furthermore, renal function status significantly moderates the effect of the TyG index on all-cause mortality in community-dwelling adults.

Adeno-associated virus-mediated gene therapy for rare pediatric neurogenetic diseases: Current status and outlook. / è ºç›¸å ³ç— æ¯’ä»‹å¯¼çš„åŸºå› æ²»ç–—åœ¨å„¿ç«¥ç¥žç»é—ä¼ ç½•è§ç— ä¸­åº”ç”¨çš„çŽ°çŠ¶ä¸Žå±•æœ›.

Rare pediatric neurogenetic diseases always have early onset, no specific therapy, high mortality, and pose a severe risk to the health and survival of children. Adeno-associated virus (AAV)-mediated gene therapy, a type of disease-modifying therapy, provides a new option for the treatment of rare pediatric neurogenetic diseases and represents a significant advancement in the field. Currently, the US Food and Drug Administration (FDA) and the European Medicines Association (EMA) have approved AAV-mediated gene therapy medications for treating spinal muscular atrophy, aromatic L-amino acid decarboxylase deficiency, and Duchenne muscular dystrophy. Numerous preclinical and clinical trial research findings from recent years indicate that AAV-mediated gene therapy has a promising future in treating genetic disorders. The quick approval process for rare diseases medications may bring hope for the treatment of children with rare neurogenetic diseases. AAV-mediated gene therapy is an emerging technology with certain risks and challenges. It is necessary to establish a standardized regulatory system and a sound long-term follow-up system to evaluate the efficacy and safety of gene therapy.

Triglyceride-glucose index linked to all-cause mortality in critically ill patients: a cohort of 3026 patients.

BACKGROUND: Triglyceride-glucose (TyG) index as a reliable surrogate of insulin resistance (IR) has been shown to be related to adverse clinical outcomes in patients with acute coronary syndrome, heart failure, ischemic stroke and so on. However, the relationship between TyG index and all-cause mortality in intensive care unit (ICU) patients remains unknown. The purpose of this study was to investigate the correlation between TyG index and all-cause mortality to evaluate the impact of IR on the prognosis of this population. METHODS: This was a retrospective observational study that included 3026 patients who had an initial triglyceride and glucose data on the first day of ICU admission, and all data were extracted from the Medical Information Mart for Intensive Care III (MIMIC-III) database. These patients were grouped into quartiles (Q1-Q4) according to TyG index. The Kaplan-Meier analysis was used to compare all-cause mortality among the above four groups. Cox proportional hazards analyses were performed to examine the association between TyG index and all-cause mortality. RESULTS: During 10.46 years of follow-up, 1148 (37.9%) patients died, of which 350 (11.6%) occurred during the hospital stay and 258 (8.5%) occurred during the ICU stay. Kaplan-Meier analysis showed that the risk of all-cause mortality was significantly higher in patients with higher TyG index (log-rank P = 0.021). Multivariable Cox proportional hazards analyses showed that the TyG index was an independent risk predictor of ICU death (HR: 1.72, 95% CI 1.18-2.52, P = 0.005) and hospital death (HR: 2.19, 95% CI 1.59-3.03, P < 0.001), and each 1-unit increased in the TyG index, a 1.19-fold increase in the risk of death during the hospital stay. CONCLUSIONS: TyG index is strongly related to the all-cause mortality increasing in critically ill patients. This finding indicates that the TyG index might be useful in identifying people at high risk of ICU death and hospital death.

Association Between Different Versions of the Model for End-Stage Liver Disease Score and Contrast-Associated Acute Kidney Injury in Patients Undergoing Elective Percutaneous Coronary Intervention.

BACKGROUND: Pre-procedure liver dysfunction was associated with acute kidney injury after percutaneous coronary intervention (PCI). The aim of this study is to assess and compare the predictive value of different liver function scoring systems for contrast-associated acute kidney injury (CA-AKI) in patients undergoing elective PCI.Methods and Results:A total of 5,569 patients were retrospectively enrolled. The model for end-stage liver disease (MELD) including albumin (MELD-Albumin) score (AUC=0.661) had the strongest predictive value in comparison to the MELD score (AUC=0.627), the MELD excluding the international normalized ratio (MELD-XI) score (AUC=0.560), and the MELD including sodium (MELD-Na) score (AUC=0.652). In the fully adjusted logistic regression model, the MELD-Albumin score and the MELD-Na score were independently associated with CA-AKI regardless of whether they were treated as continuous or categorical variables; however, this was not the case for the MELD score and the MELD-XI score. Furthermore, the addition of the MELD-Albumin score significantly improved the reclassification beyond the fully adjusted logistic regression model. The study further explored the association between different versions of the MELD score and CA-AKI using restricted cubic splines and found a linear relationship between the MELD-Albumin score and the risk of CA-AKI. CONCLUSIONS: The MELD-Albumin score had the highest predictive value for CA-AKI in patients undergoing elective PCI. The addition of the MELD-Albumin score to the existing risk prediction model significantly improved the reclassification for CA-AKI.

Red blood cell distribution width predicts gastrointestinal bleeding after coronary artery bypass grafting.

BACKGROUND: Red blood cell distribution width (RDW) is highly associated with adverse clinical outcomes in many diseases. The present study aimed to evaluate the relationship between RDW and gastrointestinal bleeding (GIB) after isolated coronary artery bypass grafting (CABG). METHODS: This was a retrospective observational study that included 4473 patients who received CABG, and all the data were extracted from the Medical Information Mart for Intensive Care III database. Data collected included patient demographics, associated comorbid illnesses, laboratory parameters, and medications. The receiver operating characteristic (ROC) curve was used to determine the best cutoff value of RDW for the diagnosis of GIB. Multivariable logistic regression analysis was used to analyze the relationship between RDW and GIB. RESULTS: The incidence of GIB in patients receiving CABG was 1.1%. Quartile analyses showed a significant increase in GIB incidence at the fourth RDW quartile (> 14.3%; P < 0.001). The ROC curve analysis revealed that an RDW level > 14.1% measured on admission had 59.6% sensitivity and 69.4% specificity in predicting GIB after CABG. After adjustment for confounders, high RDW was still associated with an increased risk of GIB in patients with CABG (odds ratio = 2.83, 95% confidence interval 1.46-5.51, P = 0.002). CONCLUSIONS: Our study indicates that the elevated RDW level is associated with an increased risk of GIB after CABG, and it can be an independent predictor of GIB. The introduction of RDW to study GIB enriches the diagnosis method of GIB and ensures the rapid and accurate diagnosis of GIB.

[Application of adeno-associated virus-mediated gene therapy in lysosomal storage diseases]. / è ºç›¸å ³ç— æ¯’ä»‹å¯¼çš„åŸºå› ç–—æ³•åœ¨æº¶é ¶ä½“è´®ç§¯ç—‡ä¸­çš„åº”ç”¨.

Lysosomal storage disorders (LSDs) are a group of single-gene inherited metabolic diseases caused by defects in lysosomal enzymes or function-related proteins. Enzyme replacement therapy is the main treatment method in clinical practice, but it has a poor effect in patients with neurological symptoms. With the rapid development of multi-omics, sequencing technology, and bioengineering, gene therapy has been applied in patients with LSDs. As one of the vectors of gene therapy, adeno-associated virus (AAV) has good prospects in the treatment of genetic and metabolic diseases. More and more studies have shown that AAV-mediated gene therapy is effective in LSDs. This article reviews the application of AAV-mediated gene therapy in LSDs.

Global DNA hypermethylation in down syndrome placenta.

Down syndrome (DS), commonly caused by an extra copy of chromosome 21 (chr21), occurs in approximately one out of 700 live births. Precisely how an extra chr21 causes over 80 clinically defined phenotypes is not yet clear. Reduced representation bisulfite sequencing (RRBS) analysis at single base resolution revealed DNA hypermethylation in all autosomes in DS samples. We hypothesize that such global hypermethylation may be mediated by down-regulation of TET family genes involved in DNA demethylation, and down-regulation of REST/NRSF involved in transcriptional and epigenetic regulation. Genes located on chr21 were up-regulated by an average of 53% in DS compared to normal villi, while genes with promoter hypermethylation were modestly down-regulated. DNA methylation perturbation was conserved in DS placenta villi and in adult DS peripheral blood leukocytes, and enriched for genes known to be causally associated with DS phenotypes. Our data suggest that global epigenetic changes may occur early in development and contribute to DS phenotypes.

Improved reduced representation bisulfite sequencing for epigenomic profiling of clinical samples.

BACKGROUND: DNA methylation plays crucial roles in epigenetic gene regulation in normal development and disease pathogenesis. Efficient and accurate quantification of DNA methylation at single base resolution can greatly advance the knowledge of disease mechanisms and be used to identify potential biomarkers. We developed an improved pipeline based on reduced representation bisulfite sequencing (RRBS) for cost-effective genome-wide quantification of DNA methylation at single base resolution. A selection of two restriction enzymes (TaqαI and MspI) enables a more unbiased coverage of genomic regions of different CpG densities. We further developed a highly automated software package to analyze bisulfite sequencing results from the Solexa GAIIx system. RESULTS: With two sequencing lanes, we were able to quantify ~1.8 million individual CpG sites at a minimum sequencing depth of 10. Overall, about 76.7% of CpG islands, 54.9% of CpG island shores and 52.2% of core promoters in the human genome were covered with at least 3 CpG sites per region. CONCLUSIONS: With this new pipeline, it is now possible to perform whole-genome DNA methylation analysis at single base resolution for a large number of samples for understanding how DNA methylation and its changes are involved in development, differentiation, and disease pathogenesis.

Ascorbic acid promoted sulfadimidine degradation in the magnetite-activated persulfate system by facilitating the Fe(III)/Fe(II) cycle.

Persulfate (PS) activation technologies were of significant importance to the organic contaminant treatment. In this study, ascorbic acid (AA) was introduced to the traditional PS-activated process by using magnetite (Fe3O4) as the activator; herein, the degradation efficiency of sulfadimidine (SM2) was improved from 30 to 93% within 3 h, and the observed removal rate was about 8.0 times higher than that of the Fe3O4/PS system. These improvements were found to be induced by the added AA because it could reduce the surface Fe(III) to Fe(II) on Fe3O4 and thus facilitate the Fe(III)/Fe(II) cycle, which was conducive to producing reactive oxygen species (ROSs) in the oxidation process during PS activation. Meanwhile, AA could also promote the Fe(III)/Fe(II) cycle in the homogeneous solution, further advancing the PS decomposition for SM2 degradation. The ROS trapping experiments indicated that SM2 removal in the Fe3O4/PS/AA system was attributed to •OH and •SO4-, and •SO4- was the dominant ROS. Moreover, the reusability test experiment revealed that magnetite retained good activity after five cycles in the Fe3O4/AA/PS system. This study provides a promising PS activation technology for efficient organics contaminant treatment.

Association between the cardiometabolic index and chronic kidney disease: a cross-sectional study.

BACKGROUND: Central obesity is a risk factor for chronic kidney disease (CKD). However, the exact correlation between the cardiometabolic index (CMI), an indicator of central obesity, and CKD remains unclear. Here, we aimed to investigate the correlation between the CMI and CKD in the general American population. METHODS: This cross-sectional study involved 64,313 members of the general population (≥ 20 years of age) with data in the National Health and Nutrition Examination Survey (NHANES) 1999-2020. The individuals were grouped into three categories by CMI tertile: T1 group (n = 7,029), T2 group (n = 7,356), and T3 group (n = 7,380). Logistic regression analysis was performed, with NHANES recommended weights, to assess the association between the CMI and CKD. RESULTS: A total of 21,765 participants were included; the overall prevalence of CKD was 12.2%. From the low to the high CMI tertile, the prevalence of CKD increased from 8.9% to 16.0% (P < 0.001). After full adjustment for confounders, the higher tertile of CMI (OR: 1.08, 95% CI: 1.03 - 1.13, P = 0.002) had the higher risk of CKD. Compared with the T1 group, the groups with higher CMI levels had a higher CKD risk (T2: OR: 1.01, 95%CI: 0.87-1.18, P = 0.812; T3: OR: 1.22, 95%CI: 1.05-1.43, P = 0.013). CONCLUSIONS: Higher CMI was independently associated with higher CKD risk in the general population.

The efficacy and safety of neoadjuvant chemoradiotherapy combined with immunotherapy for locally advanced rectal cancer patients: a systematic review.

Background: Several studies have explored the effectiveness of PD-1/PD-L1 inhibitors combined with neoadjuvant chemoradiotherapy (nCRT) in the treatment of locally advanced rectal cancer(LARC), particularly in microsatellite stable(MSS) or mismatch repair proficient(pMMR) LARC patients. We undertook a single-arm systematic review to comprehensively evaluate the advantages and potential risks associated with the use of PD-1/PD-L1 inhibitors in conjunction with nCRT for patients diagnosed with locally advanced rectal cancer. Methods: The PubMed, Embase, Cochrane Library, ClinicalTrials.gov, ASCO and ESMO were searched for related studies. The main outcomes were pathologic complete response (pCR), major pathological response (MPR), anal preservation, and adverse effects (AEs). Results: Fourteen articles including 533 locally advanced rectal cancer (LARC) patients were analyzed. The pooled pCR, MPR, and anal preservation rates were 36%, 66% and 86%. Grade ≥3 adverse events occurred in 20%. Subgroup analysis showed that; dMMR/MSI-H had a pooled pCR (100%) and MPR (100%), pMMR/MSS had a pooled pCR (38%) and MPR (60%); the short-course radiotherapy and long-course radiotherapy had pooled pCR rates of 51% and 30%, respectively. The rates of pCR for the concurrent and sequential immuno-chemoradiotherapy subgroups at 30% and 40%, mirroring pCR rates for the PD-L1 and PD-1 inhibitor subgroups were 32% and 40%, respectively. Conclusion: In cases of locally advanced rectal cancer, PD-1/PD-L1 inhibitors combined with neoadjuvant chemoradiotherapy have shown promising response rates and acceptable toxicity profiles. PD-1/PD-L1 inhibitors combined with neoadjuvant chemoradiotherapy hence has a positive outcome even in MSS LARC patients. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/#myprospero, identifier CRD42023465380.

Effect of Missed Post-Procedure Creatinine Measurement on Sub-Acute Kidney Injury Following Coronary Angiography.

Serum creatinine (SCr) levels are essential for the diagnosis of kidney disease after coronary angiography (CAG). However, the influence of missed post-procedure SCr measurement in this situation is unclear. The present study included 14,127 patients undergoing CAG as part of the Cardiorenal ImprovemeNt registry II. Patients were divided into two groups according to whether a post-procedure SCr was measured within 3 days. The primary endpoint was acute kidney disease (AKD). Logistic regression was used to evaluate the relationship between post-procedure SCr and AKD. Of the 14,127 patients (61.6 ± 9.8 years, 34.2% females), 55.4% (n = 7822) did not have a post-procedure SCr measurement. The incidence of AKD was higher in the missed post-procedure SCr group (15.7 vs 11.9%; median follow-up 6.54 years). Multivariate logistic regression showed that missed post-procedure SCr measurement was associated with significantly higher risk of AKD (adjusted odds ratio [aOR]: 1.26, 95% CI: 1.10-1.45, P < .001). The results were more significant in patients with normal renal function at baseline (aOR: 1.36, 95% CI: 1.16-1.60, P < .001). In our study, over half of the patients undergoing CAG missed their post-procedure SCr measurement. The missed post-procedure SCr group had a significantly higher risk of developing AKD compared with those with a post-procedure SCr measurement.

A V-shaped association between high-density lipoprotein cholesterol levels and poor outcomes in patients after percutaneous coronary intervention.

BACKGROUND: High density lipoprotein cholesterol (HDL-C) is considered as "good cholesterol". Recent evidence suggests that a high HDL-C level may increase the risk of poor outcomes in some populations. PURPOSE: To investigate the association between HDL-C levels and poor outcomes in patients after percutaneous coronary intervention (PCI). METHODS: Patients undergoing PCI during January 2012 and December 2018 were consecutively recruited and divided into three groups with different HDL-C levels: HDL-C ≤ 25 mg/dL, 25 < HDL-C ≤ 60 mg/dL, HDL-C > 60 mg/dL by the restricted cubic spline (RCS) analysis and assessed for all-cause mortality (ACM). The association between HDL-C levels and poor outcomes was assessed by multivariable cox regression analysis. RESULTS: The patients were followed with a median duration of 4 years. Of the 7284 participants, 727 all-cause deaths and 334 cardiovascular deaths occurred. A V-shaped association of HDL-C with the prognosis was observed, patients with either excessively low or high HDL-C levels reporting a higher risk than those with midrange values. After adjustment for confounding factors, the former exhibited a higher cumulative rate of ACM and cardiovascular mortality (CM) than the latter [low HDL-C: for ACM, hazard ratio (HR), 1.96; 95%CI, 1.41, 2.73, P < 0.001; for CM, HR, 1.66; 95%CI, 1.03, 2.67; P = 0.037; high HDL-C: for ACM, HR, 1.73; 95%CI, 1.29, 2.32, P < 0.001; for CM, HR, 1.73; 95%CI, 1.16, 2.58; P = 0.007]. CONCLUSION: HDL-C levels display a V-shaped association with poor outcomes in patients after PCI, with excessively high or low HDL-C suggesting a higher mortality risk. An optimal HDL-C level may fall in the range of 25-60 mg/dL.

Expanding the genetic and phenotypic relevance of CLCN4 variants in neurodevelopmental condition: 13 new patients.

OBJECTIVES: CLCN4 variations have recently been identified as a genetic cause of X-linked neurodevelopmental disorders. This study aims to broaden the phenotypic spectrum of CLCN4-related condition and correlate it with functional consequences of CLCN4 variants. METHODS: We described 13 individuals with CLCN4-related neurodevelopmental disorder. We analyzed the functional consequence of the unreported variants using heterologous expression, biochemistry, confocal fluorescent microscopy, patch-clamp electrophysiology, and minigene splicing assay. RESULTS: We identified five novel (p.R41W, p.L348V, p.G480R, p.R603W, c.1576 + 5G > A) and three known (p.T203I, p.V275M, p.A555V) pathogenic CLCN4 variants in 13 Chinese patients. The p.V275M variant is found at high frequency and seen in four unrelated individuals. All had global developmental delay (GDD)/intellectual disability (ID). Seizures were present in eight individuals, and 62.5% of them developed refractory epilepsy. Five individuals without seizures showed moderate to severe GDD/ID. Developmental delay precedes seizure onset in most patients. The variants p.R41W, p.L348V, and p.R603W compromise the anion/exchange function of ClC-4. p.R41W partially impairs ClC-3/ClC-4 association. p.G480R reduces ClC-4 expression levels and impairs the heterodimerization with ClC-3. The c.1576 + 5G > A variant causes 22 bp deletion of exon 10. CONCLUSIONS: We further define and broaden the clinical and mutational spectrum of CLCN4-related neurodevelopmental conditions. The p.V275M variant may be a potential hotspot CLCN4 variant in Chinese patients. The five novel variants cause loss of function of ClC-4. Transport dysfunction, protein instability, intracellular trafficking defect, or failure of ClC-4 to oligomerize may contribute to the pathophysiological events leading to CLCN4-related neurodevelopmental disorder.

DNMT1 and AIM1 Imprinting in human placenta revealed through a genome-wide screen for allele-specific DNA methylation.

BACKGROUND: Genomic imprinting is an epigenetically regulated process wherein genes are expressed in a parent-of-origin specific manner. Many imprinted genes were initially identified in mice; some of these were subsequently shown not to be imprinted in humans. Such discrepancy reflects developmental, morphological and physiological differences between mouse and human tissues. This is particularly relevant for the placenta. Study of genomic imprinting thus needs to be carried out in a species and developmental stage-specific manner. We describe here a new strategy to study allele-specific DNA methylation in the human placenta for the discovery of novel imprinted genes. RESULTS: Using this methodology, we confirmed 16 differentially methylated regions (DMRs) associated with known imprinted genes. We chose 28 genomic regions for further testing and identified two imprinted genes (DNMT1 and AIM1). Both genes showed maternal allele-specific methylation and paternal allele-specific transcription. Imprinted expression for AIM1 was conserved in the cynomolgus macaque placenta, but not in other macaque tissues or in the mouse. CONCLUSIONS: Our study indicates that while there are many genomic regions with allele-specific methylation in tissues like the placenta, only a small sub-set of them are associated with allele-specific transcription, suggesting alternative functions for such genomic regions. Nonetheless, novel tissue-specific imprinted genes remain to be discovered in humans. Their identification may help us better understand embryonic and fetal development.