A Rapid PCR-Based Diagnostic Method for Skin Infection with Mycobacterium marinum.

Objective: The increasing incidence of chronic skin infections caused by Mycobacterium marinum, coupled with the time-consuming and low detection rates nature of traditional culture and histological-based diagnostic methods, underscores the need for an expedited approach. The study aims to develop a rapid and efficient method for detecting M. marinum with PCR technology. Methods: We designed four pairs of primers based on DNA sequences from GeneBank and prior studies, we utilized both PCR and Real-time PCR to identify M. marinum. Specificity and sensitivity assessments were conducted in vitro by DNAs extracted from M. marinum and other bacterial or fungal cultures. Further validation was performed through the implementation of a mouse skin infection model to optimize and confirm the efficacy of the detection method in both fresh and paraffin-embedded skin tissues. The same PCR testing system was further confirmed with paraffin-embedded skin tissues samples from patients as well. Results: The results of the study indicate promising outcomes for the four-pair primers system. It demonstrated 100% sensitivity in detecting M. marinum from purified cultures, including typical strains and nine clinical isolates, while achieving a specificity of 100%. This specificity was evidenced by the absence of PCR products from 12 bacterial species, 12 fungi species, and six other non-tuberculous mycobacterium (NTM) species. In the animal model, the PCR assay exhibited high detection efficacy for both infected fresh tissues and paraffin-embedded tissues, with a slight superiority observed in fresh tissues. However, the PCR assay exhibited high detection efficacy for clinical paraffin-embedded tissues. These findings collectively underscore the robust detection capabilities of our four-pair primers in both in vitro and in vivo settings. Conclusion: A sensitive and highly specific rapid detection system has been successfully developed that can be used to detect M. marinum in both infected fresh tissues and paraffin-embedded tissues.

Epidemiologic features and therapeutic strategies of kerion: A nationwide multicentre study.

BACKGROUND: Kerion is a severe type of tinea capitis that is difficult to treat and remains a public health problem. OBJECTIVES: To evaluate the epidemiologic features and efficacy of different treatment schemes from real-world experience. METHODS: From 2019 to 2021, 316 patients diagnosed with kerion at 32 tertiary Chinese hospitals were enrolled. We analysed the data of each patient, including clinical characteristics, causative pathogens, treatments and outcomes. RESULTS: Preschool children were predominantly affected and were more likely to have zoophilic infection. The most common pathogen in China was Microsporum canis. Atopic dermatitis (AD), animal contact, endothrix infection and geophilic pathogens were linked with kerion occurrence. In terms of treatment, itraconazole was the most applied antifungal agent and reduced the time to mycological cure. A total of 22.5% of patients received systemic glucocorticoids simultaneously, which reduced the time to complete symptom relief. Furthermore, glucocorticoids combined with itraconazole had better treatment efficacy, with a higher rate and shorter time to achieving mycological cure. CONCLUSIONS: Kerion often affects preschoolers and leads to serious sequelae, with AD, animal contact, and endothrix infection as potential risk factors. Glucocorticoids, especially those combined with itraconazole, had better treatment efficacy.

Excessive weight gain onset-age and risk of developing diabetes mellitus: a large, prospective Chinese cohort study.

Background: Excessive weight gain and obesity are widely accepted as risk factors for diabetes mellitus, and the age at which obesity onsets may be related to the development of cardiovascular diseases and certain cancers. Here, we aimed to investigate associations between the onset-age of overweight/obesity and risk of developing diabetes mellitus in China. Methods: 42,144 people with the normal weight range and without diabetes at baseline, were enrolled from the Kailuan cohort which began on the 1st June 2006. All participants were followed-up, biennially, until 31st December 2017. During follow-up, 11,220 participants had become overweight/obese. For each case, one normal-weight control was matched according to age ( ± 1 year) and sex. Our final analysis included 10,858 case-control pairs. An age-scaled Cox model was implemented to estimate hazard ratios (HR) with corresponding 95% confidence intervals (CI) for diabetes mellitus incidence across age-groups. Results: At a median follow-up of 5.46 years, 1,403 cases of diabetes mellitus were identified. After multivariate adjustments, age-scaled Cox modelling suggested that risk gradually attenuated with every 10 year increase in age of onset of overweight/obesity. Diabetes mellitus adjusted HRs (aHRs) for new-onset overweight/obesity at <45years, 45-54 years, and 55-64 years were 1.47 (95%CI, 1.12-1.93), 1.38 (95%CI, 1.13-1.68), 1.32 (95%CI, 1.09-1.59), respectively. However, new-onset of overweight/obesity at ≥65 years did not relate to diabetes mellitus (aHR, 1.20; 95%CI, 0.92-1.57). This trend was not observed in women or the new-onset obesity subgroup but was evident in men and the new overweight onset subgroup. Conclusion: Participants with early onset of excessive weight gain issues are at considerably higher risk of developing diabetes mellitus compared to those who maintain a normal weight.

Combined effect of adiposity and elevated inflammation on incident type 2 diabetes: a prospective cohort study.

BACKGROUND: Adiposity and elevated inflammation are two hallmarks of hyperglycemia. However, it is unknown whether clustering of elevated inflammation and adiposity interact act on diabetogenesis and lead to a greater risk for incident type 2 diabetes (T2D). METHODS: Adiposity was indicated by body mass index, waist circumference and ultrasonography-measured fatty liver degrees. Elevated inflammation was indicated as high-sensitivity C-reactive protein levels ≥ 2 mg/L. Time-to-event survival analyses were conducted to investigate the joint effect of adiposity and inflammation on incident T2D on both multiplicative and additive scales. RESULTS: Among 82,172 non-diabetic participants from a prospective cohort in China, 14,278 T2D occurred over a median follow-up of 11 years. In the multivariable-adjusted model, elevated inflammation [1.12 (1.08‒1.16)] and adiposity [1.76 (1.69‒1.83) for overweight/obesity, 1.49 (1.44‒1.55) for central obesity, and 2.02 (1.95‒2.09) for fatty liver] were significantly associated with incident diabetes. Higher adiposity-associated risks and incidence rates of diabetes were observed with elevated inflammation. When studying the joint effect, the adjusted HRs were 1.77 (1.69‒1.85) for overweight/obesity, 1.14 (1.06‒1.23) for elevated inflammation, and 2.08 (1.97‒2.19) for their joint effect, with a relative excess risk due to interaction of 0.17 (0.05‒0.28). The attributable proportions were 71.30% for overweight/obesity, 12.96% for elevated inflammation, and 15.74% for their interaction. Similar results were observed when adiposity was assessed as waist circumference or fatty liver. CONCLUSIONS: Adiposity and elevated inflammation synergically lead to greater risks of incident diabetes than addition of each individual exposure. Strategies simultaneously targeting both risks should produce more benefits for diabetes prevention than through initiatives directed at each separate risk.

Temporal relationship between triglyceride-glucose index and blood pressure and their joint cumulative effect on cardiovascular disease risk: a longitudinal cohort study.

BACKGROUND: Concurrent insulin resistance and elevated blood pressure are commonly observed in cardiovascular disease (CVD) and have long been proposed to contribute to CVD. However, the temporal relationship between them and the effect of their cumulative co-exposure on future incident CVD remains unclear. METHODS: Longitudinal analysis of data on 57,192 participants from a real-world, prospective cohort study (Kailuan Study) was performed to address the temporal relationship between Triglyceride-Glucose Index (TyG, calculated as ln [TG (mg/dL) × FBG (mg/dL)/2]) and blood pressure (BP) assessed by cross-lagged analyses in an approximately 4-year exposure period (2006/2007 to 2010/2011). After excluding 879 participants with known diabetes, 56,313 nonCVD participants were included for further analysis of the CVD outcome. Cox regression models were used to examine the hazard ratios (HRs) upon the cumulative TyG (CumTyG) and BP(CumBP) in the exposure period. RESULTS: The standard regression coefficient from baseline TyG to follow-up systolic BP was 0.0142 (95% CI 0.0059-0.0226), which was greater than the standard regression coefficient from baseline systolic BP to follow-up TyG (- 0.0390; 95% CI - 0.0469 to - 0.0311). The same results were observed in the cross-lag between TyG and diastolic blood pressure [0.0271 (0.0185 to 0.0356) vs. - 0.0372 (- 0.0451 to - 0.0293)]. During a median follow-up of 9.98 years, 3981 CVD cases occurred. Significant interactions were observed between the median CumTyG (8.61) and CumSBP thresholds (130, 140 mmHg) (P = 0.0149), the median CumTyG (8.61) and CumDBP thresholds (80, 90 mmHg) (P = 0.0441). Compared to CumTyG < 8.61 and CumSBP < 130 mmHg, after adjusting for potential confounding factors, the HR gradually increased in the high co-exposure groups. The hazard ratios (HRs) and 95% confidence intervals (CIs) for Q2-Q6 were 1.39 (1.24, 1.57), 1.94 (1.69, 2.22), 2.40 (2.12, 2.71), 2.74 (2.43, 3.10), and 3.07 (2.74, 3.45). Additionally, the CVD risks in the co-exposure were more prominent in younger participants. CONCLUSIONS: These findings suggest that elevated TyG has a greater impact on future blood pressure changes than vice versa. Dual assessment and management of insulin resistance and blood pressure contribute to the prevention of CVD, especially in younger individuals.

Relationship between the cumulative exposure to atherogenic index of plasma and ischemic stroke: a retrospective cohort study.

BACKGROUND: Atherogenic index of plasma (AIP) has been demonstrated as a surrogate marker for ischemic stroke, but there is limited evidence for the effect of long-term elevation of AIP on ischemic stroke. Therefore, we aimed to characterize the relationship between cumulative exposure to AIP and the risk of ischemic stroke. METHODS: A total of 54,123 participants in the Kailuan Study who attended consecutive health examinations in 2006, 2008, and 2010 and had no history of ischemic stroke or cancer were included. The time-weighted cumulative AIP (cumAIP) was calculated as a weighted sum of the mean AIP values for each time interval and then normalized to the total duration of exposure (2006-2010). Participants were divided into four groups according to quartile of cumAIP: the Q1 group, ≤-0.50; Q2 group, - 0.50 to - 0.12; Q3 group, - 0.12 to 0.28; and Q4 group, ≥ 0.28. Cox proportional hazard models were used to evaluate the relationship between cumAIP and ischemic stroke by calculating hazard ratios (HRs) and 95% confidence intervals (95% CIs). RESULTS: After a median follow-up of 11.03 years, a total of 2,742 new ischemic stroke events occurred. The risk of ischemic stroke increased with increasing quartile of cumAIP. After adjustment for potential confounders, Cox regression models showed that participants in the Q2, Q3, and Q4 groups had significantly higher risks of ischemic stroke than those in the Q1 group. The HRs (95% CIs) for ischemic stroke in the Q2, Q3, and Q4 groups were 1.17 (1.03, 1.32), 1.33 (1.18, 1.50), and 1.45 (1.28, 1.64), respectively. The longer duration of high AIP exposure was significantly associated with increased ischemic stroke risk. CONCLUSIONS: High cumulative AIP is associated with a higher risk of ischemic stroke, which implies that the long-term monitoring and maintenance of an appropriate AIP may help prevent such events.

Accumulated exposure to high non-high-density lipoprotein cholesterol increases the risk of cardiovascular diseases in hypertensive individuals: An 11-year prospective cohort study.

BACKGROUND: The relationship of cumulative non high-density lipoprotein-cholesterol (Cum-non-HDL-C) concentration with the risk of cardiovascular disease (CVD) in individuals with hypertension remains unclear. METHODS: In total 27 234 participants for whom three consecutive total cholesterol and HDL-C concentrations were available, and who did not have CVD, comprising 13 617 with hypertension and 13 617 without from 2006 to 2010. Participants were placed into four groups according to Cum-non-HDL-C. Cox proportional hazards models were used to evaluate the relationship between Cum-non-HDL-C and the risk of CVD. RESULTS: Over a median 11 years, 1,298 participants with hypertension developed CVD. After adjustment for multiple potential confounding factors, compared with participants with hypertension and Cum-non-HDL-C < 130 mg/dl, the fully adjusted hazard ratios and 95% confidence intervals of CVD associated with Cum-non-HDL-C values of 130-159 mg/dl, 160-189 mg/dl, and ≥ 190 mg/dl were 1.23 (1.01, 1.34), 1.27 (1.04, 1.56), and 1.51 (1.13, 2.01), respectively. Compared with participants without hypertension and a Cum-non-HDL-C < 130 mg/dl, the fully adjusted hazard ratios (95% confidence intervals) for the participants with hypertension and Cum-non-HDL-Cs < 130 mg/dl, 130-159 mg/dl, 160-189 mg/dl, and ≥ 190 mg/dl were 1.84 (1.55, 2.18), 2.16 (1.81, 2.59), 2.17 (1.73, 2.70), and 2.45 (1.12, 3.29), respectively. CONCLUSIONS: A consistently high non-HDL-C concentration increases the risk of CVD in individuals with hypertension, as does prolonged exposure to a high non-HDL-C concentration. Thus, the achievement of target blood pressure and non-HDL-C concentrations should help reduce the risk of CVD in individuals with hypertension.

Relationship between cumulative exposure to triglyceride-glucose index and heart failure: a prospective cohort study.

BACKGROUND: High triglyceride-glucose index (TyG) is a major risk factor for heart failure, but the long-term effect of high TyG index on the risk of developing heart failure remains unclear. Therefore, we aimed to determine the relationship between the cumulative exposure to TyG index and the risk of heart failure. METHODS: A total of 56,149 participants from the Kailuan Study, who participated in three consecutive health examinations in 2006, 2008, and 2010 and had no history of heart failure or cancer were recruited for this study. The cumulative TyG index was calculated as the weighted sum (value × time) of the mean TyG index for each time interval. The participants were placed into quartiles based on their cumulative TyG index. The study ended on December 31, 2020, and the primary outcome was new-onset heart failure during the follow-up period. In addition, a Cox proportional hazards regression model and a restricted cubic spline analysis were used to further evaluate the relationship between cumulative TyG index and the risk of heart failure. RESULTS: During a median follow-up period of 10.04 years, a total of 1,312 new heart failure events occurred. After adjustment for potential confounding factors, the Cox regression analysis showed that the hazard ratios (95% confidence intervals) for the risk of heart failure in the Q2, Q3, and Q4 groups were 1.02 (0.83,1.25), 1.29 (1.07,1.56) and 1.40 (1.15,1.71), respectively, vs. the Q1 group. The subgroup analysis showed a significant interaction between cumulative TyG index and BMI or waist circumference, but there was no interaction between age, sex and cumulative TyG index. The restricted cubic spline analysis showed a dose-response relationship between cumulative TyG index and the risk of heart failure. In addition, the sensitivity analysis generated results that were consistent with the primary results. CONCLUSIONS: High cumulative TyG index is associated with a higher risk of heart failure. Thus, the TyG index may be useful for the identification of individuals at high risk of heart failure. The present findings emphasize the importance of the long-term monitoring of the TyG index in clinical practice.

Cumulative exposure to high remnant-cholesterol concentrations increases the risk of cardiovascular disease in patients with hypertension: a prospective cohort study.

BACKGROUND: The relationship of cumulative remnant-cholesterol (Cum-RC) concentration with the risk of cardiovascular disease (CVD) in patients with hypertension remains unclear. METHODS: We studied data for 28,698 individuals for whom three consecutive total cholesterol, high-density lipoprotein-cholesterol (HDL-C), and triglyceride concentrations were available, and who did not have CVD (14,349 with hypertension and 14,349 without), that was collected between 2006 and 2010. Participants with hypertension were placed into four groups based on Cum-RC quartile: a Q1 group (< 26.40 mg/dl), a Q2 group (26.40-39.56 mg/dl), a Q3 group (39.57-54.65 mg/dl), and a Q4 group (≥ 54.66 mg/dl). Cox proportional hazards models were used to evaluate the relationship between Cum-RC and the risk of CVD. RESULTS: Over a median 10.9 (interquartile range, 10.5-11.3) years, 1,444 participants with hypertension developed CVD. After adjustment for multiple potential confounding factors, and compared with the Q1 Cum-RC group of the participants with hypertension, the adjusted hazard ratios for CVD for the Q2-Q4 groups were 1.07(0.92,1.26), 1.08(0.91,1.28), and 1.26(1.03,1.54) (P = 0.0405); those for myocardial infarction were 1.51(1.00,2.31), 2.02(1.22,3.27), and 2.08(1.41,3.28) (P < 0.0001); and those for ischemic stroke were 1.02(0.84,1.24), 1.04(0.86,1.25), and 1.29(1.02,1.62), respectively (P = 0.0336). However, no significant relationship was found between Cum-RC and the risk of hemorrhage stroke. At the same Cum-RC, the risk of CVD was significantly higher in participants with hypertension than in those without. CONCLUSIONS: A consistently high remnant-cholesterol concentration increases the risk of CVD in individuals with hypertension. Therefore, the achievement of blood pressure and RC concentration targets should help reduce the risk of CVD in individuals with hypertension.

Identification of ESM1 as a Potential Biomarker Involving Drug Sensitivity and the Tumor Immune Microenvironment that Promotes Proliferation of Melanoma.

ESM1 may play a role in human cancers, but its role in melanoma remains unclear. This study investigated ESM1 expression in Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases and confirmed it through immunohistochemistry (IHC) and Western blotting (WB). Using the ESM1 gene expression levels, we divided TCGA samples into high and low-expression groups and identified differentially expressed genes (DEGs) between them. We then performed GO and KEGG enrichment analyses on these DEGs and explored the immune landscape while identifying anti-tumor drugs. ESM1 was found to be highly expressed in metastatic melanoma compared to primary melanoma and normal tissues. This was associated with increased numbers of immune-related cells and genes, as well as the activation of tumor progression pathways such as Notch and Wnt. In the high ESM1 expression group, the number of multiple immune-related cells and the expression of immune-related genes correlated with the presentation of ESM1, as well as the agonism of pathways related to tumor progressions. Immunohistochemistry and WB demonstrated a significant increase in ESM1 expression in metastatic lesions. Multiple GEO datasets showed higher ESM1 mRNA expression in malignant melanoma than in other benign tumors. ESM1 knockdown in a mouse model reduced tumor volume and weight related to the Wnt/-catenin and NOTCH signaling pathways. So, ESM1 is a promising biomarker for drug sensitivity, the tumor immune microenvironment, and the proliferation of cutaneous melanoma.

Comparative analysis of allergenicity and predicted linear epitopes in α and ß parvalbumin from turbot (Scophthalmus maximus).

BACKGROUND: Parvalbumin (PV) can be subdivided into two phylogenetic lineages, αPV and ßPV. The bony fish ßPV is considered a major fish allergen. However, there is no available report on the immunological property and epitope mapping of bony fish αPV. RESULTS: To characterize the allergenic property of bony fish αPV and investigate the difference in allergenic property of bony fish αPV and ßPV, turbot (Scophthalmus maximus) αPV and ßPV were identified by mass spectrometry and were expressed in Escherichia coli system in this study. Spectra analysis and three-dimensional (3D) modeling showed the similar structure between αPV and ßPV. However, αPV exhibited lower immunoglobulin E/immunoglobulin G (IgE/IgG) binding capacity than ßPV. Three identified ßPV epitopes possessed higher IgE reactivity and more hydrophobic residues than three identified αPV epitopes. In addition, less similarity in sequence homology of αPV epitopes was observed with allergen sequences in database. CONCLUSION: These finding expanded information on fish PV epitopes and substantiated the difference in allergenicity and epitope mapping between fish αPV and ßPV, which will improve the epitope-based detection tools of PV and diagnostic of PV induced fish allergy. © 2023 Society of Chemical Industry.

Temporal relationship between atherogenic dyslipidemia and inflammation and their joint cumulative effect on type 2 diabetes onset: a longitudinal cohort study.

BACKGROUND: Concurrent atherogenic dyslipidemia and elevated inflammation are commonly observed in overt hyperglycemia and have long been proposed to contribute to diabetogenesis. However, the temporal relationship between them and the effect of their cumulative co-exposure on future incident type 2 diabetes (T2D) remains unclear. METHODS: Longitudinal analysis of data on 52,224 participants from a real-world, prospective cohort study (Kailuan Study) was performed to address the temporal relationship between high-sensitivity C-reactive protein (hsCRP) and the atherogenic index of plasma (AIP, calculated as triglyceride/high-density lipoprotein) in an approximately 4-year exposure period (2006/2007 to 2010/2011). After excluding 8824 participants with known diabetes, 43,360 nondiabetic participants were included for further analysis of the T2D outcome. Cox regression models were used to examine the adjusted hazard ratios (aHRs) upon the cumulative hsCRP (CumCRP) and AIP (CumAIP) in the exposure period. RESULTS: In temporal analysis, the adjusted standardized correlation coefficient (ß1) of hsCRP_2006/2007 and AIP_2010/2011 was 0.0740 (95% CI, 0.0659 to 0.0820; P < 0.001), whereas the standardized correlation coefficient (ß2) of AIP_2006/2007 and hsCRP_2010/2011 was - 0.0293 (95% CI, - 0.0385 to - 0.0201; P < 0.001), which was significantly less than ß1 (P < 0.001). During a median follow-up of 7.9 years, 5,118 T2D cases occurred. Isolated exposure to CumAIP or CumCRP was dose-dependently associated with T2D risks, independent of traditional risk factors. Significant interactions were observed between the median CumAIP (- 0.0701) and CumCRP thresholds (1, 3 mg/L) (P = 0.0308). Compared to CumAIP < - 0.0701 and CumCRP < 1 mg/L, those in the same CumAIP stratum but with increasing CumCRP levels had an approximately 1.5-fold higher T2D risk; those in higher CumAIP stratum had significantly higher aHRs (95% CIs): 1.64 (1.45-1.86), 1.87 (1.68-2.09), and 2.04 (1.81-2.30), respectively, in the CumCRP < 1, 1 ≤ CumCRP < 3, CumCRP ≥ 3 mg/L strata. Additionally, the T2D risks in the co-exposure were more prominent in nonhypertensive, nondyslipidemic, nonprediabetic, or female participants. CONCLUSIONS: These findings suggest a stronger association between elevated hsCRP and future AIP changes than vice versa and highlight the urgent need for combined assessment and management of chronic inflammation and atherogenic dyslipidemia in primary prevention, particularly for those with subclinical risks of T2D.

Factors associated with post-treatment control of viral load in HIV-infected patients: a systematic review and meta-analysis.

OBJECTIVES: This study aimed to investigate the factors associated with maintenance of viral suppression after antiretroviral therapy (ART) discontinuation. METHODS: Databases were searched for studies published between January 01, 2011, and July 01, 2022, that correlated the time of virus rebound with treatment interruption (TI). The corresponding data were extracted from these studies. A fixed-effects model was used to calculate pooled estimates. RESULTS: Thirty-one studies were included in this analysis. Results showed that patients who started ART during acute or early infection had longer viral control than those who started ART during chronic infection. It has been reported that some broadly neutralizing HIV-1-specific antibodies can significantly prolong viral inhibition. The study also found that approximately 7.2% of patients achieved post-treatment control (PTC) approximately a year after TI. CONCLUSION: ART initiation in the acute or early phases can delay viral rebound after TI. Cell-associated HIV RNA and HIV DNA have been difficult to prove as able to predict viral rebound time. Many vaccines and antibodies have also been shown to be effective in prolonging viral control in people without PTC, and more research is needed to develop alternative ART therapies that can effectively inhibit or even eliminate HIV.

Effect of Aerobic Exercise on Arterial Stiffness in Individuals with Different Smoking Statuses.

This study aimed to investigate the immediate effects of acute bout of aerobic exercise on arterial stiffness in individuals with different smoking statuses. A total of 940 male individuals (mean age of 36.82±7.76 years) in the Kailuan study cohort were selected to participate in the fifth National Physical Fitness Monitoring. All participants completed measurements of brachial - ankle pulse wave velocity (baPWV) before and after twice-quantitative cycle ergometer exercise. Four groups were defined: (1) non-smokers (n=231), (2) former smokers (n=165), (3) light smokers (1-10 cigarettes/day, n=254), (4) heavy smokers (>10 cigarettes/day, n=290). Generalized linear models were established to analyze between-group differences in the change in baPWV before and after acute aerobic exercise in individuals with different smoking statuses. Overall, after acute aerobic exercise, baPWV was immediately decreased significantly (-33.55 cm/s [95% CI, - 39.69 to -27.42]). Compared with non-smokers, former smokers, light smokers, and heavy smokers showed a greater decrease in baPWV (-12.17 cm/s [95%CI, - 30.08 to 5.75], - 18.43 cm/s [95%CI, -34.69 to - 2.16], and -22.46 cm/s [95%CI, - 38.39 to - 6.54]) respectively. There is a transient decrease in baPWV in individuals with different smoking statuses. Compared with non-smokers, baPWV decreased more significantly in light and heavy smokers.

Estimated pulse wave velocity can predict the incidence of new-onset atrial fibrillation: A 11-year prospective study in a Chinese population.

Background: Arterial stiffness, a risk factor for atrial fibrillation (AF), is rarely applied in clinical practice because of the difficulty and high cost of its measurement. Estimated pulse wave velocity (ePWV) is a simple, reproducible, and non-invasive index of arterial stiffness. This study was to assess the predictive value of ePWV for the risk of new-onset AF. Methods: Subjects were selected from the Kailuan cohort study population who underwent initial physical examination between 2006 and 2008. A total of 96,561 subjects were ultimately included in the final analysis. ePWV was divided into four groups according to quartiles. The Kaplan-Meier method was used to calculate the cumulative incidence of AF. A Cox regression model was used to assess the predictive value of estimated arterial stiffness for new-onset AF. Results: Mean age of subjects was 51.47 ± 9.68 years, while 76,968 (79.65%) were male and 19,663 (20.35%) were female. During mean follow-up period of 11.77 years, 1,215 AF events occurred. Results of the Kaplan-Meier analysis showed that the incidence of new-onset AF increased with increase in ePWV. Cox regression analysis showed that in the total population, the incidence of new-onset AF was 1.64, 1.90, and 2.64 times higher in the medium, medium-high, and high ePWV groups, respectively, compared with the low ePWV group. When stratified according to sex, ePWV had higher predictive value in the female population. Conclusions: Increased ePWV increases the incidence of new-onset AF, and may promote application of more aggressive primary prevention. Trial registry name: Risk factors and intervention for cardiology, cerebrovascular and related disease (Kailuan Study); URL: http://www.chictr.org.cn/showproj.aspx?proj=8050; Registration number: ChiCTR-TNRC-11001489.

Association of Cardiovascular Health Score Trajectory With Incident Myocardial Infarction in Hypertensive Patients.

BACKGROUND: The association between changes in cardiovascular health score (CHS) over time and myocardial infarction (MI) risk in hypertensive patients remains unclear. METHOD: This was a prospective study comprising 17 374 hypertensive patients from the Kailuan study cohort who underwent 3 surveys and were identified to be free of MI, stroke, or cancer from 2006 to 2010. CHS consisted of 7 cardiovascular health metrics (plasma glucose, total cholesterol, blood pressure, smoking, body mass index, physical activity, salt intake), ranging from 0 (worst) to 13 (best) in the study. CHS trajectories were developed during 2006 to 2010 to predict the MI risk from 2010 to 2020. Additionally, the Cox proportional hazard model was established to calculate the hazard ratio and 95% CI of incident MI in different trajectory groups. RESULT: This study identified the 5 CHS trajectories from 2006 to 2010: low-stable (n=1161; range, 4.7-4.5), moderate-decreasing (n=3928; decreased from 6.9 to 6.0), moderate-increasing (n=1014; increased from 5.6 to 7.8), high-stable I (n=7940; range, 8.1-8.2), and high-stable II (n=3331; range, 9.2-9.7). During the median follow-up of 10.04 years, 288 incident MI cases were identified. After adjusting for potential confounders, compared with low-stable group, the hazard ratio and 95% CI of MI were 0.24 (0.15-0.40) for high-stable II, 0.36 (0.24-0.54) for high-stable I, 0.46 (0.25-0.83) for moderate-increasing, and 0.61 (0.41-0.90) for moderate-decreasing, respectively. CONCLUSIONS: In hypertensive patients, high-stable CHS or improvement in CHS is associated with a lower risk of incident MI, when compared with low-stable CHS trajectory over time.

Changes in Impaired Fasting Glucose and Borderline High Low-Density Lipoprotein-Cholesterol Status Alter the Risk of Cardiovascular Disease: A 9-Year Prospective Cohort Study.

Background: We aimed to characterize the relationships of the changes in impaired fasting glucose (IFG) and borderline high low-density lipoprotein-cholesterol (LDL-C) status with cardiovascular disease (CVD). Methods: A total of 36,537 participants who did not have previous CVD, diabetes mellitus, or high LDL-C (≥ 4.1 mmol/L), nor were taking lipid-lowering drugs were recruited from the Kailuan study. The participants were allocated to six groups according to their baseline and follow-up fasting blood glucose (FBG) and LDL-C concentrations: (1) both were normal; (2) both normal at baseline, one abnormality subsequently; (3) both normal at baseline, both abnormal subsequently; (4) at least one abnormality that became normal; (5) at least one abnormality at baseline, a single abnormality subsequently; and (6) at least one abnormality, two abnormalities subsequently. The outcomes were CVD and subtypes of CVD (myocardial infarction and stroke). Multiple Cox regression models were used to calculate adjusted hazard ratio (HR) and confidence interval (95% CI). Results: During a median follow-up period of 9.00 years, 1,753 participants experienced a CVD event. After adjustment for covariates, participants with IFG in combination with a borderline high LDL-C status at baseline and follow-up had higher risks of CVD (HR: 1.52; 95% CI: 1.04-2.23 and HR: 1.38, 95% CI: 1.13-1.70, respectively) compared with those with normal fasting blood glucose and LDL-C. Compared with participants that remained normal, those who changed from normality to having two abnormalities were at a higher risk of CVD (HR: 1.26; 95% CI: 0.98-1.61), as were those who changed from at least one abnormality to two abnormalities (HR: 1.48, 95% CI: 1.02-2.15). Conclusion: Changes in IFG and borderline high LDL-C status alter the risk of CVD and its subtype, implying that it is important to focus on such individuals for the prevention and control of CVD.

Triglyceride-glucose index trajectory and stroke incidence in patients with hypertension: a prospective cohort study.

BACKGROUND: It has been suggested that the baseline triglyceride-glucose (TyG) index, a simple surrogate measure for insulin resistance, is significantly associated with the occurrence of stroke. Nevertheless, the impact of longitudinal patterns of TyG on the stroke risk in hypertensive patients is still unknown. Hence, this study aimed to investigate the association between TyG index trajectory and stroke risk among hypertensive patients. METHODS: This prospective study included 19,924 hypertensive patients from the Kailuan Study who underwent three waves survey and were free of myocardial infarction, cancer and stroke before or during 2010. The TyG index was calculated as ln [fasting triglyceride (mg/dL) × fasting plasma glucose (mg/dL)/2], and latent mixed modelling was used to identify the trajectory of TyG during the exposure period (2006-2010). Furthermore, the Cox proportional hazard models were applied to estimate the hazard ratio (HR) and 95% confidence interval (CI) for incident stroke of different trajectory groups. RESULTS: Five distinct TyG trajectory were identified during 2006-2010: low-stable (n = 2483; range, 8.03-8.06), moderate low-stable (n = 9666; range, 8.58-8.57), moderate high-stable (n = 5759; range, 9.16-9.09), elevated-stable (n = 1741; range, 9.79-9.75), and elevated-increasing (n = 275; range, 10.38-10.81). During the median follow-up of 9.97 years, 1,519 cases of incident stroke were identified, including 1,351 with ischemic stroke and 215 with hemorrhage stroke. After adjusting for confounding variables, the HR and 95% CI of stroke were 2.21 (1.49,3.28) for the elevated-increasing group, 1.43 (1.13,1.83) for the elevated-stable group, 1.35 (1.10,1.64) for the moderate high-stable group, 1.26 (1.06,1.52) for the moderate low-stable group, respectively, when compare with the low-stable group. Similar results were observed in ischemic stroke, but a significant association was not found between TyG trajectory and risk of hemorrhage stroke. CONCLUSION: A long-term elevated TyG index in hypertensive patients is associated with an increased risk of stroke, especially ischemic stroke. This finding implies that regular monitoring of TyG index may assist in identifying individuals at a higher risk of stroke among patients with hypertension.

Comparison of the Efficacy and Safety of a Doravirine-Based, Three-Drug Regimen in Treatment-Naïve HIV-1 Positive Adults: A Bayesian Network Meta-Analysis.

Introduction: Extensive use of antiretroviral therapy has remarkably improved the survival rates of people living with HIV. Doravirine (DOR) is a newly-approved antiretroviral belonging to the class of non-nucleoside reverse transcriptase inhibitors. Here, we compared the efficacy and safety of DOR + tenofovir dipivoxil fumarate (TDF)+Lamivudine (3TC)/Emtritabine (FTC) with traditional triple therapies in treatment-naïve HIV-1-positive adults. Methods: Randomized controlled trials involving treatment-naïve HIV-1-positive adults that met inclusion criteria were systematically retrieved and data on the following outcomes extracted: virological suppression, adverse events, severe adverse events, and drug-related adverse events. A Bayesian network meta-analysis was then performed on the data. Results: This study included a total of 39 randomized controlled trials involving 26 antiretroviral therapies and 21,110 HIV1-positive patients. At week 48, relative to the other 25 regimens included in the network of virological suppression, DOR + TDF+3TC/FTC exhibited superiority to some efavirenz, nevirapine, atazanavir, or lopinavir-based regimens, including efavirenz + abacavir+3TC [Odd Ratio (OR) = 0.52, 95% confidence interval (CrI) = 0.35-0.77]. At week 48, the performance of DOR + TDF+3TC/FTC was relatively similar to all other analyzed regimens in terms of adverse events. The DOR + TDF+3TC/FTC regimen performed better in terms of severe adverse events and drug-related adverse events. Conclusion: The network meta-analysis showed that DOR + TDF+3TC/FTC has good efficacy and safety at 48 weeks. Systematic Review Registration: Open Science Framework, https://osf.io/6ybp7.