Polymer-free dual drug-eluting stents evaluated in a porcine model.

BACKGROUND: Although drug-eluting stents have dramatically reduced the rates of restenosis and target lesion revascularization, they are associated with stent thrombosis (ST), a catastrophic event likely due to delayed endothelialization and chronic inflammation caused by the polymer and the metal scaffolds. To increase the safety and efficacy of stents, polymer-free dual drug-eluting stents (DDES) have been developed. METHODS: A total 160 stents (Bare-metal stents (BMS), polymer-free probucol stents (PrES), sirolimus-eluting stents (SES) and DDES) were randomly implanted in the coronary arteries of 80 pigs. 14, 28, 90 and 191 days after implantation, QCA and OCT evaluations were performed in 20 pigs respectively, and the arteries were harvested for scanning electron microscope (SEM), histomorphology, histopathology analyses and for the relative expression of CD31, CD34 and CD133 on mRNA and protein levels. RESULTS: At the 14-day time point, there were significant differences in the strut rate coverage (p = 0.011), with greater coverage in the PrES than in the SES group (53.2%vs. 20.3%, p = 0.002). As well, there were no significant differences in the expression of CD31, CD34 and CD133 between groups in mRNA and protein level. CONCLUSIONS: DDES were as safe as BMS and SES, but they did not further improve the endothelialization of the stented coronary arteries in the porcine model.

[An analysis of etiologies of fever of unknown origin in 372 patients].

OBJECTIVE: To analyze the etiology of fever of unknown origin (FUO). METHODS: A total of 372 patients with FUO who hospitalized in Capital Medical University Affiliated Beijing Friendship Hospital were retrospectively analyzed from January 2003 to August 2013. All the patients were divided into two groups: group A (January 2003 - December 2007) and group B (January 2008-August 2013). Diagnosis rate, duration of hospitalization (days) and time to diagnosis between the two groups were artificially compared. RESULTS: Of the 372 FUO cases, 336 were positively diagnosed with a diagnosis rate of 90.3%. Infectious diseases were still the primary causes of FUO (60.2%), including 72 cases (32.1%) of tuberculosis. Connective tissue diseases accounted for 12.9% of the FUO cases, malignancies were 8.3%, and miscellaneous diseases were 8.9%. Yet thirty six patients (9.7%) could not be confirmed until they were discharged from hospital. The duration of fever in patients with malignancies was longer than that with infectious diseases [60.0 (30.0, 90.0) days vs 30.0 (20.0, 60.0) days, P = 0.003]. Time to diagnosis of connective tissue disease and malignancies was longer than infectious diseases [(12.0(7.3, 18.8) days and 11.0 (7.0, 18.0) vs 5.0 (3.0, 8.0) days, both P values = 0.000]. The duration of hospitalization in group A was longer than that of group B [17.0(12.0, 30.0) days vs 14.0(10.0, 20.0) days, P = 0.000]. The diagnosis rate and time to diagnosis of group A were similar with those of group B. The proportion of connective tissue diseases in group A was higher than group B (18.1% vs 9.2%,χ(2) = 6.201, P = 0.013) . The proportion of infectious disease, malignancies and miscellaneous diseases was not significantly different between the two groups. CONCLUSIONS: Infectious diseases are the major causes of FUO, and the most common cause is tuberculosis. Connective tissue diseases and malignancies are the second and third causes of FUO. The duration of fever and time to diagnosis are significantly different between the different origins.

The prevalence and determinant of overweight and obesity among residents aged 40-69 years in high-risk regions for upper gastrointestinal cancer in southeast China.

Being overweight or obese is one of the public health concerns worldwide, and its prevalence is gradually increasing. Obesity has been proven to be associated with some cancers, including upper gastrointestinal cancer (UGC). However, studies on the prevalence of obesity among residents of areas at high risk of UGC in China are minimal. The aim of this study is to assess the prevalence of obesity and its influencing factors among people aged 40-69 years (high-risk population) in high-risk areas for UGC in Jiangsu Province, southeast China. This cross-sectional study involved 45,036 subjects aged 40-69 years identified in the Rural Early Diagnosis and Treatment of UGC Project database in Jiangsu Province from 2017 to 2021. Differences in prevalence across gender and age were assessed using the Chi-square test. Using a multinomial logistic regression model, we examined independent risk factors for overweight/obesity and their gender and age differences. The prevalence of overweight, obesity, and overweight/obesity varied based on the standards used: Chinese standard (42.1%, 11.9%, and 54.0%) and WHO standard (34.7%, 4.7%, and 39.4%), respectively. Being overweight was more common in men than women, while obesity was more common in women than men. Age of 50-59 years, married, household size of 7-9, drinking, soy products, pickled food, and hot food intake were positively associated with overweight/obesity. Females, 60-69 years, higher education level, household size of 4-6, annual family income of more than 60,000 CNY, smoking, and fresh fruit intake were negatively associated with overweight/obesity. Stratified analysis showed that the effects of age, education and meat, egg and dairy products on overweight/obesity were different across gender. The impact of fresh fruit and vegetables on overweight/obesity was also heterogeneous between the younger (40-59 years) and older (60-69 years) groups. In conclusion, the prevalence of overweight and obesity is high among adults aged 40-69 years from high-risk areas for UGC of Jiangsu Province, southeast China. Independent influencing factors of being overweight/obese included gender, age, marital status, education, household size, annual family income, smoking, drinking, fresh fruit, soy products, pickled food and hot food intake, and may vary by gender and age. Screening-based interventions should be considered to control obesity levels among screened participants. Besides, heterogeneity of influencing factors across subgroups could be focused on to improve intervention effectiveness.

Safety and efficacy of a novel 3D-printed bioresorbable sirolimus-eluting scaffold in a porcine model.

Background: The effect of 3D-printed bioresorbable vascular scaffolds (BRS) in coronary heart disease has not been clarified. Aims: We aimed to compare the safety and efficacy of 3D-printed BRS with that of metallic sirolimus-eluting stents (SES). Methods: Thirty-two BRS and 32 SES were implanted into 64 porcine coronary arteries. Quantitative coronary angiography (QCA) and optical coherence tomography (OCT) were performed at 14, 28, 97, and 189 days post-implantation. Scanning electron microscopy (SEM) and histopathological analyses were performed at each assessment. Results: All stents/scaffolds were successfully implanted. All animals survived for the duration of the study. QCA showed the two devices had a similar stent/scaffold-to-artery ratio and acute percent recoil. OCT showed the lumen area (LA) and scaffold/stent area (SA) of the BRS were significantly smaller than those of the SES at 14 and 28 days post-implantation (14-day LA: BRS vs SES 4.52±0.41 mm2 vs 5.69±1.11 mm2; p=0.03; 14-day SA: BRS vs SES 4.99±0.45 mm2 vs 6.11±1.06 mm2; p=0.03; 28-day LA: BRS vs SES 2.93±1.03 mm2 vs 4.82±0.74 mm2; p=0.003; 28-day SA: BRS vs SES 3.86±0.98 mm2 vs 5.75±0.71 mm2; p=0.03). Both the LA and SA of the BRS increased over time and were similar to those of the SES at the 97-day and 189-day assessments. SEM and histomorphological analyses showed no significant between-group differences in endothelialisation at each assessment. Conclusions: The novel 3D-printed BRS showed safety and efficacy similar to that of SES in a porcine model. The BRS also showed a long-term positive remodelling effect.

Case report: Torsade de pointes induced by the bigeminy result from retrograde ventriculoatrial activation in VVI pacing and resolved by intentional atrial pacing.

Introduction: While pacing has been used for long QT syndrome (LQTs), the optimal pacing modality is controversial. Case: We report a woman with bradycardia and a recently implanted single-chamber pacemaker experienced multiple syncope. No device dysfunction was found. Multiple Torsade de Pointes (TdP) induced by the bigeminy result from retrograde ventriculoatrial (VA) activation in VVI pacing were demonstrated in the scenario of previously unidentified LQTs. Replacement for a dual-chamber ICD and intentional atrial pacing eliminated the VA conduction and symptoms. Conclusion: Pacing without atrioventricular sequence might be catastrophic in LQTs. Atrial pacing and atrioventricular synchrony should be highlighted.

Case Report: Systemic Amyloidosis Involving the Heart and Skeletal Muscle.

Background: Amyloidosis refers to an etiologically heterogeneous group of protein misfolding diseases characterized by extracellular deposition in organs and tissues of amyloid fibers, leading to severe organ dysfunction and death. Systemic amyloidosis often involves multiple organs. Heart and kidney are the most commonly affected organs, whereas skeletal muscle involvement is rare and often accompanied by other organs' involvement. Case Summary: We reported a 70-year-old man manifested with myopathy followed by heart failure who was suspected of transthyretin amyloidosis clinically, after the pathological results and the 99mTc-pyrophosphate (99mTc-PYP) scintigraphy, light-chain (AL) amyloidosis involving the heart and skeletal muscle was confirmed. Conclusion: The patient's unique presentation gives insight into a rare but debilitating disorder and the potential link between various types of amyloidosis. In addition, myopathy in amyloidosis should be recognized.

Effect of indobufen vs. aspirin on platelet accumulation in patients with stable coronary heart disease after percutaneous coronary intervention: An open-label crossover study.

Purpose: This study compared the effect of indobufen with that of aspirin on platelet function in patients with stable coronary heart disease after percutaneous coronary intervention (PCI). Methods: Patients with stable coronary heart disease who had undergone PCI and received dual antiplatelet therapy (aspirin 100 mg + clopidogrel 75 mg once daily) for at least 12 months were allocated to receive indobufen 100 mg twice daily + clopidogrel 75 mg once daily, clopidogrel 75 mg once daily alone, indobufen 100 mg twice daily alone, and aspirin 100 mg once daily alone for 1 month each in an open-label crossover manner. Platelet function was assessed by using the rates of arachidonic acid (AA)-induced platelet aggregation (AA-PAR) and adenosine diphosphate (ADP)-induced platelet aggregation (ADP-PAR) measured by light transmission aggregometry, the platelet reactivity index measured by vasodilator-stimulated phosphoprotein (PRI-VASP), and the plasma and urinary thromboxane B2 (TXB2) concentrations recorded at baseline and during each treatment phase. Results: Of 56 patients enrolled, 52 completed the study. The AA-PAR was lower in the indobufen alone group than in the aspirin alone group [5.21% (3.39, 7.98) vs. 5.27% (4.06, 6.60), p = 0.038], while biologically, a difference of 0.06% may represent no significant difference; there was no significant between-group difference in the plasma [531.16 pg/ml (203.89, 1035.06) vs. 373.93 pg/ml (194.04, 681.71), p = 0.251] or urinary [3951.97 pg/ml (2006.95, 6077.01) vs. 3610.48 pg/ml (1664.60, 6247.61), p = 0.717] TXB2 concentration. When the aspirin + clopidogrel group and indobufen + clopidogrel group were compared, similar results were found for AA-PAR [3.97% (3.05, 5.12) vs. 3.83% (3.10, 5.59), p = 0.947] and both plasma [849.47 pg/ml (335.96, 1634.54) vs. 455.41 pg/ml (212.47, 1489.60), p = 0.629], and urinary [4122.97 pg/ml (2044.96, 7459.86) vs. 3812.81 pg/ml (1358.95, 6021.07), p = 0.165] TXB2 concentrations. ADP-PAR was lower in the clopidogrel alone group than in the indobufen alone group (47.04% ± 16.89 vs. 61.7% ± 10.50, p < 0.001), as was PRI-VASP (66.53% ± 18.06 vs. 77.72% ± 19.87, p = 0.002). Conclusion: These findings suggest that indobufen has antiplatelet effects similar to those of aspirin in patients with stable coronary heart disease after PCI, and may be an alternative for patients with aspirin intolerance after coronary stenting.

Cardiotonic Pills® protects from myocardial fibrosis caused by in stent restenosis in miniature pigs.

BACKGROUND: Stent implantation has been increasingly applied for the treatment of obstructive coronary artery disease, which, albeit effective, often harasses patients by in-stent restenosis (ISR). PURPOSE: The present study was to explore the role of compound Chinese medicine Cardiotonic Pills® (CP) in attenuating ISR-evoked myocardial injury and fibrosis. STUDY DESIGN: Chinese miniature pigs were used to establish ISR model by implanting obsolete degradable stents into coronary arteries. Quantitative coronary angiography (QCA) was performed to confirm the success of the model. METHODS: CP was given at 0.2 g/kg daily for 30 days after ISR. On day 30 and 60 after stent implantation, the myocardial infarct and myocardial blood flow (MBF) were assessed. Myocardial histology was evaluated by hematoxylin-eosin and Masson's trichrome staining. The content of ATP, MPO, and the activity of mitochondrial respiratory chain complex Ⅳ were determined by ELISA. Western blot was performed to assess the expression of ATP5D and related signaling proteins, and the mediators of myocardial fibrosis. RESULTS: Treatment with CP diminished myocardial infarct size, retained myocardium structure, attenuated myocardial fibrosis, and restored MBF. CP ameliorated energy metabolism disorder, attenuated TGFß1 up-regulation and reversed its downstream gene expression, such as Smad6 and Smad7, and inhibited the increased expression of MCP-1, PR S19, MMP-2 and MMP-9. CONCLUSION: CP effectively protects myocardial structure and function from ISR challenge, possibly by regulating energy metabolism via inactivation of RhoA/ROCK signaling pathway and inhibition of monocyte chemotaxis and TGF ß1/Smads signaling pathway.

Association of Plasma Vitamin B6 With Coronary Heart Disease in Patients Undergoing Diagnostic Coronary Angiography: New Insight on Sex Differences.

Aim: To date, findings on the overall and sex-specific effects of plasma pyridoxal 5'-phosphate (PLP, active coenzyme form of vitamin B6) on the risk of coronary heart disease (CHD) have been inconsistent. This study sought to advance our understanding on the association of plasma PLP with risk of CHD, with particular attention paid to sex differences and effect modifiers. Methods: We conducted a hospital-based, case-control study on suspected CHD patients undergoing diagnostic coronary angiography. A total of 429 CHD cases and 429 controls matched by age, sex, and operation time were included in the final analysis. Plasma PLP was assessed using LC-MS. Logistic regression analyses were performed to evaluate the association between plasma PLP and a first CHD event. Results: The mean (SD) plasma PLP levels were 8.4 (6.3) in male cases and 9.0 (11.0) in female cases, and 9.5 (8.5) in male controls and 12.5 (12.9) in female controls. Each 1 ng/mL increment in log2PLP was associated with a 28% lower risk of CHD in overall population. When stratified by sex, plasma PLP was significantly and independently associated with CHD in women (OR = 0.63, 95% CI: 0.50-0.80), but not in men (OR = 0.86, 95% CI: 0.67-1.09). The association of plasma PLP with CHD risk was modified by sex (adjusted P interaction = 0.022). Conclusions: We found a significant, inverse linear association between plasma PLP and CHD in Chinese women, but not in men. Our findings warrant additional investigation.

Exome-Wide Association Study Reveals Several Susceptibility Genes and Pathways Associated With Acute Coronary Syndromes in Han Chinese.

Genome-wide association studies have identified more than 150 susceptibility loci for coronary artery disease (CAD); however, there is still a large proportion of missing heritability remaining to be investigated. This study sought to identify population-based genetic variation associated with acute coronary syndromes (ACS) in individuals of Chinese Han descent. We proposed a novel strategy integrating a well-developed risk prediction model into control selection in order to lower the potential misclassification bias and increase the statistical power. An exome-wide association analysis was performed for 1,669 ACS patients and 1,935 healthy controls. Promising variants were further replicated using the existing in silico dataset. Additionally, we performed gene- and pathway-based analyses to investigate the aggregate effect of multiple variants within the same genes or pathways. Although none of the association signals were consistent across studies after Bonferroni correction, one promising variant, rs10409124 at STRN4, showed potential impact on ACS in both European and East Asian populations. Gene-based analysis explored four genes (ANXA7, ZNF655, ZNF347, and ZNF750) that showed evidence for association with ACS after multiple test correction, and identification of ZNF655 was successfully replicated by another dataset. Pathway-based analysis revealed that 32 potential pathways might be involved in the pathogenesis of ACS. Our study identified several candidate genes and pathways associated with ACS. Future studies are needed to further validate these findings and explore these genes and pathways as potential therapeutic targets in ACS.

Renal impact of high-loading-dose statin pre-cardiac catheterization in patients with chronic kidney disease and long-term statin use.

Previous studies have reported that short-term statin loading effectively protects statin-naive patients with mild renal insufficiency from contrast-induced acute kidney injury (CI-AKI). The aim of the present study was to determine whether patients with more advanced chronic kidney disease (CKD) and long-term statin therapy also benefit from high-loading statin pretreatment. A total of 256 consecutive patients with moderate-to-severe CKD receiving long-term statin therapy and undergoing percutaneous coronary intervention (PCI) or coronary artery angiography (CAG) were divided into the statin-loading group (n=34) and the no statin-loading group (n=222), depending on whether the respective patient received high-dose statin within 24 h prior to the intervention. The primary endpoint was the percent change in serum creatinine (SCr) levels. Additional endpoints included absolute change in SCr levels, estimated glomerular filtration rate (eGFR) at 48-72 h after contrast exposure, incidence rate of CI-AKI and composite in-hospital adverse events. The mean SCr decreased from baseline in either of the two groups, and the differences in the percent (P=0.930) and absolute change (P=0.990) in SCr levels were not significant between the two groups. Furthermore, no significant difference in the post-procedural eGFR was observed between the two groups. The incidence rates of CI-AKI (2.9 vs. 4.1%, P>0.999) and in-hospital adverse events (0.0 vs. 3.6%, P=0.602) were also similar between the two groups. Stratified analyses were then performed, which yielded results consistent with the above. Multiple linear regression indicated that the baseline eGFR value and current smoking status were independent factors affecting the post-procedural eGFR value, while high-dose statin loading was not. Therefore, statin reloading prior to intervention may not provide any further renal protection or decrease the occurrence of in-hospital adverse events in patients with moderate-to-severe CKD receiving long-term statin therapy, which warrants validation in prospective trials.

Diagnostic Value of PCT and CRP for Detecting Serious Bacterial Infections in Patients With Fever of Unknown Origin: A Systematic Review and Meta-analysis.

BACKGROUND: It is vital to recognize the cause of an infection to enable earlier treatment. Studies have shown that procalcitonin (PCT) and C-reactive protein (CRP) have very high sensitivity and specificity for diagnosing serious bacterial infections (SBIs), with PCT performing better than CRP. METHODS: Multiple databases were searched for relevant studies, and full-text articles involving diagnosis with PCT and CRP were reviewed. All meta-analyses were conducted with Review Manager 5.0. Sensitivity and bias analyses were performed to evaluate the quality of articles. In addition, a funnel plot and Egger test were used to assess possible publication bias. RESULT: A total of 17 articles met the criteria for inclusion. The concentrations of both PCT and CRP were higher in the SBI group than in the nonbacterial infection group. Sensitivity for differentiating bacterial infections from nonbacterial infections was higher for PCT compared with CRP, whereas there was no significant difference in specificity. The area under the summary receiver operating characteristic curve for PCT was larger than that for CRP. CONCLUSION: Both PCT and CRP are useful markers and should be used to evaluate SBIs with fever of unknown origin.

Weight reduction via life-style modifications results in reverse remodelling and cardiac functional improvement in a patient with obesity.

The prevalence of obesity has increased strikingly in recent years. Obesity is associated with increased left ventricular end-diastolic dimension (LVEDD), ventricular wall thickness, left ventricular (LV) mass, left atrial diameter, subtle myocardial systolic as well as diastolic dysfunction and has been identified as an independent predictor of these changes. It's convinced that weight reduction results in cardiac reverse remodelling, while the functional changes after weight reduction are variable. Here, we present a recent case of man with moderate obesity who acquires favourable regression in chamber size, wall thickness and significant improvement in cardiac function. Briefly, after life-style modifications and comprehensive secondary prevention, great amounts of weight loss was achieved simultaneously with decreased LVEDD and increased LV ejection fraction. As dietary intervention and regular physical activity are pivotal for these benefits, this non-invasive approach for weight loss should be advocated in selected patients.

Evaluation of promoting effect of a novel Cu-bearing metal stent on endothelialization process from in vitro and in vivo studies.

Drug eluting stents (DES) have been extensively applied nowadays and reduce the incidence of in-stent restenosis (ISR) greatly as compared with bare metal stents (BMS). However, the development of DES is hindered by the risk of late stent thrombosis (LST) due to delayed re-endothelialization, while endothelialization is an important process related to ISR and LST after implantation. 316L is a traditional stent material without bioactivity and have a high risk of ISR. Cu is recognized for angiogenesis stimulation in these years. Hence a copper bearing 316L stainless steel (316L-Cu) was prepared and evaluated about its effect on endothelialization in this paper. Compared with traditional 316L, it was proved that 316L-Cu increased the proliferation of co-cultured human umbilical vein endothelial cells (HUVECs) at first day. Moreover, HUVECs stretched better on the surface of 316L-Cu. It also improved the expression of angiogenesis related genes and tube formation ability in vitro. 316L-Cu-BMS, DES and 316L-BMS were implanted in swine to evaluate the re-endothelialization ability in vivo. And 316L-Cu-BMS showed the best effect on endothelialization with good biosafety. Consequently, 316L-Cu is a kind of promising BMS material for coronary field.

Enhanced in Vitro and in Vivo Performance of Mg-Zn-Y-Nd Alloy Achieved with APTES Pretreatment for Drug-Eluting Vascular Stent Application.

Bioabsorbable magnesium alloys are becoming prominent as temporary functional implants, as they avoid the risks generated by permanent metallic implants such as persistent inflammation and late restenosis. Nevertheless, the overfast corrosion of Mg alloys under physiological conditions hinders their wider application as medical implant materials. Here we investigate a simple one-step process to introduce a cross-linked 3-amino-propyltrimethoxysilane (APTES) silane physical barrier layer on the surface of Mg-Zn-Y-Nd alloys prior to electrostatic spraying with rapamycin-eluting poly(lactic-co-glycolic acid) (PLGA) layer. Surface microstructure was characterized by scanning electron microscope and Fourier transform infrared spectroscopy. Nanoscratch test verified the superior adhesion strength of PLGA coating in the group pretreated with APTES. Electrochemical tests combined with long-term immersion results suggested that the preferable in vitro anticorrosion behavior could be achieved by dense APTES barrier. Cell morphology and proliferation data demonstrated that APTES pretreated group resulted in remarkably preferable compatibility for both human umbilical vein endothelial cells and vascular smooth muscle cells. On the basis of excellent in vitro mechenical property, the animal study on the APTES pretreated Mg-Zn-Y-Nd stent implanted into porcine coronary arteries confirmed benign tissue compatibility as well as re-endothelialization without thrombogenesis or in-stent restenosis at six-month followup.