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.

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.

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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.

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.

Non-Invasive Liver Fibrosis Scores Are Associated With Contrast-Associated Acute Kidney Injury in Patients Undergoing Elective Percutaneous Coronary Intervention.

Previous studies have demonstrated that non-invasive liver fibrosis scores (LFSs) are associated with kidney function deterioration. This study aimed to assess the predictive performance of LFSs in contrast-associated acute kidney injury (CA-AKI) in coronary artery disease (CAD) patients undergoing elective percutaneous coronary intervention (PCI). This retrospective study involved 5627 patients. The frequency of CA-AKI was 6.3% (n = 353). In a multivariate logistic analysis after adjustment, non-invasive LFSs, including fibrosis-5 score (FIB-5), fibrosis-4 score (FIB-4), aspartate aminotransferase to alanine aminotransferase ratio (AAR), and aspartate aminotransferase to platelet ratio index were independent risk factors for CA-AKI (all P < .05), whereas the Forns score was not (P > .05). The highest predictive performance was observed for FIB-5 (area under the curve [AUC] = .644) compared to other LFSs. A restricted cubic spline analysis confirmed approximately linear relationships between LFSs and risks of CA-AKI. Furthermore, adding FIB-5 (AUC = .747; net reclassification improvement [NRI] = .441, P < .001; integrated discrimination improvement [IDI] = .008, P < .001) or AAR (AUC = .747; NRI = .419, P < .001; IDI = .006, P = .010) to an established clinical risk model could significantly improve the prediction of CA-AKI. The LFSs were significantly associated with CA-AKI, possibly serving as predictive tools for early identification of CAD patients undergoing elective PCI that are at high risk of CA-AKI.

Prognostic Value of Different Versions of the Model for End-Stage Liver Disease Score in Patients Undergoing Percutaneous Coronary Intervention.

The model for end-stage liver disease (MELD) score, which can reflect liver and renal function, is associated with poor prognosis. However, the prognostic performance of the modified MELD score in patients undergoing elective percutaneous coronary intervention (PCI) has not been fully evaluated and compared. This study retrospectively enrolled 5324 patients. During a median follow-up of 2.85 years, 412 patients died. Time-dependent receiver operating characteristic curves at 3 years indicated that the MELD including albumin (MELD-Albumin) score had the highest prognostic performance (AUC = .721) than the MELD score (AUC = .630), the MELD excluding the international normalized ratio (MELD-XI) score (AUC = .606), and the MELD including sodium (MELD-Na) score (AUC = .656) (all P < .001). The MELD-Albumin score, the MELD score, and the MELD-Na score were independent predictors of long-term mortality; however, the MELD-XI score was not when treated as a categorical variable (P = .254). Adding the MELD-Albumin score to the model of clinical risk factors could improve the prognostic performance. For the subgroup analysis, the association between the MELD-Albumin score and long-term mortality was more pronounced in patients ≤75 years (interaction P value = .005). The MELD-Albumin score showed the strongest prognostic performance than the other versions of the MELD score in patients undergoing elective PCI.

Calcitonin gene-related peptide is potential therapeutic target of osteoporosis.

Osteoporosis is a skeletal disorder characterised by the decrease of bone mineral density and is becoming prevalent with the entry of an ageing era. There are two catalogues of osteoporosis, including primary osteoporosis and secondary osteoporosis, according to the pathological causes. Since the demonstrations of osteoporosis are usually covered by other diseases, its therapeutic strategies are not satisfactory for both patients and clinicians. Calcitonin gene-related peptide (CGRP) is a peptide expressed in both bone tissues and peripheral nerves innervating bone tissue, and its expression in osteoporosis patients is increased. Recent studies have indicated that CGRP could promote the osteogenesis by osteblasts and bone absorption by osteoclasts, thus maintaining the bone homeostasis. The effects of CGRP on bone homeostasis are related with its promotion of angiogenesis through vascular endothelial growth factor and its modulation of multiple signal pathways including receptor activator of nuclear factor kappa-Β ligand. In addition, CGRP could interact with neuronal system through neural growth factor to modulate osteoporosis. Application of implants or nanoparticles also verified the beneficial effect of CGRP on osteoporosis. There studies imply a great therapeutic potential of CGRP in treating osteoporosis. Although massive studies about CGRP in osteoporosis have been performed with positive results, there is little development in clinical application. The review summarises recent advancement in the roles of CGRP in modulating osteoporosis, which will be helpful in providing some directions for further study of CGRP in treating osteoporosis.

Association between neutrophil percentage-to-albumin ratio and contrast-associated acute kidney injury in patients without chronic kidney disease undergoing percutaneous coronary intervention.

BACKGROUND: Neutrophil and albumin are well-known biomarkers of inflammation, which are highly related to contrast-associated acute kidney injury (CA-AKI). We aim to explore the predictive value of neutrophil percentage-to-albumin ratio (NPAR) for CA-AKI and long-term mortality in patients without chronic kidney disease (CKD) undergoing elective percutaneous coronary intervention (PCI). METHODS: We retrospectively observed 5083 consenting patients from January 2012 to December 2018. CA-AKI was defined as an increase in serum creatinine ≥50% or 0.3 mg/dL within 48 h after contrast medium exposure. RESULTS: The incidence of CA-AKI was 5.6% (n=286). The optimal cut-off value of NPAR for predicting CA-AKI was 15.7 with 66.8% sensitivity and 61.9% specificity [C statistic=0.679; 95% confidence interval (CI), 0.666-0.691]. NPAR displayed higher area under the curve values in comparison to neutrophil percentage (p < 0.001) and neutrophil-to-albumin ratio (NAR) (p < 0.001), but not albumin (p = 0.063). However, NPAR significantly improved the prediction of CA-AKI assessed by the continuous net reclassification improvement (NRI) and integrated discrimination improvement (IDI) compared to neutrophil percentage (NRI=0.353, 95% CI: 0.234-0.472, p < 0.001; IDI=0.017, 95% CI: 0.010-0.024, p < 0.001) and albumin (NRI=0.141, 95% CI: 0.022-0.260, p = 0.020; IDI=0.009, 95% CI: 0.003-0.015, p = 0.003) alone. After adjusting for potential confounding factors, multivariate analysis showed that NPAR >15.7 was a strong independent predictor of CA-AKI (odds ratio =1.90, 95% CI: 1.38-2.63, p < 0.001). Additionally, NPAR >15.7 was significantly associated with long-term mortality during a median of 2.9 years of follow-up (hazard ratio =1.68, 95% CI: 1.32-2.13; p < 0.001). CONCLUSIONS: NPAR was an independent predictor of CA-AKI and long-term mortality in patients without CKD undergoing elective PCI.

Predictive value of aspartate aminotransferase-to-alanine aminotransferase ratio for contrast-associated acute kidney injury in patients undergoing elective percutaneous coronary intervention.

BACKGROUND: Pre-procedure liver insufficiency has been demonstrated as a poor prognostic factor after percutaneous coronary intervention (PCI). Recent research discovered that the aspartate aminotransferase-to-alanine aminotransferase ratio (De-Ritis ratio) reflects the severity of liver insufficiency and was associated with adverse outcomes. We aim to evaluate the predictive value of the De-Ritis ratio for contrast-associated acute kidney injury (CA-AKI) and long-term mortality in patients undergoing elective PCI. METHODS: We retrospectively enrolled 5780 consenting patients undergoing elective PCI between January 2012 and December 2018. CA-AKI was defined as an increase in serum creatinine ≥0.3 mg/dl or ≥50% within 48 h after the administration of contrast media. RESULTS: The incidence of CA-AKI was 6.3% (n = 363). The De-Ritis ratio >1.30 was identified as the best cut-off value for CA-AKI prediction. The De-Ritis ratio showed an area under the curve (AUC) of 0.636 [95% confidence interval (CI): 0.605-0.667] in predicting CA-AKI, which was significantly greater than alanine aminotransferase (p<0.001) and aspartate aminotransferase (p = 0.012) alone. Furthermore, compared to currently recognized liver function assessment tools, the predictive value of the De-Ritis ratio on CA-AKI was similar to the MELD score (AUC: 0.636 vs 0.626, p = 0.631) and higher than the MELD-XI score (AUC: 0.636 vs 0.561, p<0.001). Multivariate logistic analysis showed that the De-Ritis ratio >1.30 was independently associated with CA-AKI (odds ratio=1.551, 95% CI: 1.185-2.030, p = 0.001). The addition of the De-Ritis ratio to the fully adjusted logistic regression model has significant incremental effects on the risk prediction for CA-AKI with a continuous net reclassification improvement of 0.395 (p<0.001) and an integrated discrimination improvement of 0.005 (p = 0.018). Additionally, the De-Ritis ratio >1.30 was significantly associated with long-term mortality (hazard ratio=1.285, 95% CI: 1.007-1.641, p = 0.044). CONCLUSIONS: The De-Ritis ratio was an independent risk factor for CA-AKI and long-term mortality in patients undergoing elective PCI.

Syncope as the Initial Manifestation of Advanced Nasopharyngeal Carcinoma: A Case Report.

Carotid sinus syndrome is a principal cause of syncope in the elderly. Syncope, associated with carotid sinus syndrome which is secondary to metastasis of advanced nasopharyngeal carcinoma, rarely occurs. The current study reported a 66-year-old woman, who presented with a history of frequent and recurrent syncope as the initial symptom, and was eventually diagnosed with advanced nasopharyngeal carcinoma. The positron emission tomography scan demonstrated a diagnosis of advanced nasopharyngeal carcinoma with involvement in carotid sheath space, and nasopharyngeal biopsy revealed non-keratinized nasopharyngeal carcinoma. After diagnosis and treatment, the patient had no recurrence of syncope. In summary, our case study suggests that great importance should be attached to potential intrinsic causes of syncope especially in the case of nasopharyngeal carcinoma, as it is an insidious malignancy which needs to be precisely identified.

Case Report: A Rare Syncope Case Caused by Abernethy II and a Review of the Literature.

Background: Abernethy malformation is an extremely rare anomaly of the splanchnic venous system, and only 2 cases that manifested as syncope had been reported previously. Case Presentation: A 24-year-old male had a 15-year history of jaundice and was in long-term use of hepatoprotective drugs. He was admitted for complaint of syncope. He underwent a series of examinations and cardiac ultrasound showed that his pulmonary artery pressure was elevated. Further imaging revealed the absence of intrahepatic portal veins. His blood ammonia was significantly increased. All signs and symptoms pointed to an Abernethy diagnosis. He was finally diagnosed as having Abernethy type II. He was discharged after 17 days of in-hospital treatment with sildenafil (50 mg/day) and ornithine aspartate (20 g/day). Conclusion: We now report this rare case of syncope that is caused by Abernethy malformation. As a typically pediatric disease, it was not identified in this patient until adulthood due to long-term treatment for jaundice and liver cirrhosis. Furthermore, we present a review of portosystemic shunts previously reported in the literature.

Fentanyl Inhibits Air Puff-Evoked Sensory Information Processing in Mouse Cerebellar Neurons Recorded in vivo.

Aim: To examine the effects of fentanyl, a potent mu-opioid receptor (MOR) agonist, on-air puff-evoked responses in Purkinje cells (PCs), and molecular layer interneurons (MLIs) using in vivo patch-clamp recordings in anesthetized mice. Methods: Male mice 6-8 weeks-old were anesthetized and fixed on a custom-made stereotaxic frame. The cerebellar surface was exposed and perfused with oxygenated artificial cerebrospinal fluid (ACSF). Patch-clamp recordings in the cell-attached mode were obtained from PCs and MLIs. Facial stimulation by air-puff of the ipsilateral whisker pad was performed through a pressurized injection system. Fentanyl citrate, CTOP, and H-89 dissolved in ACSF were perfused onto the cerebellar surface. Results: Fentanyl significantly inhibited the amplitude and area under the curve (AUC) of sensory stimulation-evoked inhibitory responses in PCs. Although fentanyl did not influence the frequency of simple spikes (SSs), it decreased the pause of SS. The IC50 of the fentanyl-induced suppression of the P1 response amplitude was 5.53 µM. The selective MOR antagonist CTOP abolished fentanyl-induced inhibitory responses in PCs. However, the application of CTOP alone increased the amplitude, AUC of P1, and the pause of SS. Notably, fentanyl significantly inhibited the tactile-evoked response of MLIs but did not affect their spontaneous firing. The fentanyl-induced decrease of inhibitory responses in PCs was partially prevented by a PKA inhibitor, H-89. Conclusions: These results suggest that fentanyl binds to MORs in MLIs to reduce GABAergic neurotransmission in MLI-PC projections and one potential mechanism is via modulation of the cAMP-PKA pathway.