Functional angiography-derived index of microcirculatory resistance validated with microvascular obstruction in cardiac magnetic resonance after STEMI.

INTRODUCTION AND OBJECTIVES: The index of microcirculatory resistance (IMR) measured after primary percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI) is associated with microvascular obstruction (MVO) and adverse clinical events. To evaluate MVO after successful primary PCI for STEMI without pressure wires or hyperemic agents, we investigated the feasibility and usefulness of functional angiography-derived IMR (angio-IMR). METHODS: The current study included a total of 285 STEMI patients who underwent primary PCI and cardiac magnetic resonance (CMR). Angio-IMR of the culprit vessel after successful primary PCI was calculated using commercial software. MVO, infarct size, and myocardial salvage index were assessed using CMR, which was obtained a median of 3.0 days [interquartile range, 3.0-5.0] after primary PCI. RESULTS: Among the total population, 154 patients (54.0%) showed elevated angio-IMR (> 40 U) in the culprit vessel. MVO was significantly more prevalent in patients with angio-IMR> 40 U than in those with angio-IMR ≤ 40 U (88.3% vs 32.1%, P <.001). Infarct size, extent of MVO, and area at risk were significantly larger in patients with angio-IMR> 40 U than in those with angio-IMR ≤ 40 U (P <.001 for all). Angio-IMR showed a significantly higher discriminatory ability for the presence of MVO than thrombolysis in myocardial infarction flow grade or myocardial blush grade (area under the curve: 0.821, 0.504, and 0.496, respectively, P <.001). CONCLUSIONS: Angio-IMR was significantly associated with CMR-derived infarct size, extent of MVO, and area at risk. An elevated angio-IMR (> 40 U) after primary PCI for STEMI was highly predictive of the presence of MVO in CMR. This trial was registered at ClnicalTrialsgov (Identifier: NCT04828681).

Functional Coronary Angiography-Derived Index of Microcirculatory Resistance in Patients With ST-Segment Elevation Myocardial Infarction.

OBJECTIVES: The aim of this study was to evaluate the diagnostic accuracy and prognostic implications of angiography-derived index of microcirculatory resistance (angio-IMR) in patients with ST-segment elevation myocardial infarction (STEMI). BACKGROUND: The index of microcirculatory resistance (IMR) is a reliable invasive measure of coronary microvascular dysfunction in patients with STEMI. A functional coronary angiography-derived method to estimate IMR is a wire- and hyperemic agent-free alternative to IMR. METHODS: The study population consisted of 2 independent cohorts. The diagnostic cohort comprised patients with IMR from the culprit vessel immediately after successful primary percutaneous coronary intervention (n = 31). The prognostic cohort was patients with STEMI who were successfully treated with primary percutaneous coronary intervention and followed for 10 years from the index procedure (n = 309). Angio-IMR was calculated using computational flow and pressure simulation. The primary outcome was a composite of cardiac death and readmission for heart failure over 10 years of follow-up. RESULTS: In the diagnostic cohort, angio-IMR correlated well with IMR (R = 0.778; P < 0.001). Sensitivity, specificity, accuracy, and area under the curve of angio-IMR to predict IMR >40 U were 75.0%, 84.2%, 80.6%, and 0.899 (95% confidence interval: 0.786-0.949), respectively. In the prognostic cohort, patients with angio-IMR >40 U showed significantly higher risk for cardiac death or readmission for heart failure than did those with angio-IMR ≤40 U (46.7% vs 16.6%; adjusted hazard ratio: 2.909; 95% CI: 1.670-5.067; P < 0.001). Angio-IMR >40 U was an independent predictor of cardiac death or readmission for heart failure (hazard ratio: 2.173; 95% CI: 1.157-4.079; P = 0.016) and showed incremental prognostic value compared with a model with clinical risk factors only (C index = 0.726 vs 0.666 [P < 0.001], net reclassification index = 0.704 [P < 0.001]). CONCLUSIONS: Angio-IMR showed high correlation and diagnostic accuracy to predict IMR. Patients with STEMI with angio-IMR >40 U showed a significantly higher risk for cardiac death or readmission for heart failure than those with preserved angio-IMR values. (Prognostic Implication of Angiography-Derived IMR in STEMI Patients; NCT04628377).

The acute effects of temperature variability on heart rate variability: A repeated-measure study.

BACKGROUND: The impacts of temperature variability on cardiac autonomic function remain unclear. OBJECTIVE: To explore the short-term associations between daily temperature variability and parameters of heart rate variability (HRV). METHODS: This is a repeated-measure study among 78 eligible participants in Shanghai, China. We defined temperature variability as diurnal temperature range (DTR), the standard-deviation of temperature (SDT) and temperature variability (TV). We evaluated 3 frequency-domain HRV parameters (VLF, LF and HF) and 4 time-domain parameters (SDNN, SDANN, rMSSD and pNN50). We used linear mixed-effect models to analyze the data after controlling for environmental and individual confounders. RESULTS: Temperature variability was significantly associated with decreased HRV, especially on the concurrent day. The exposure-response relationships were almost inversely linear for most parameters. Every one interquartile range (IQR) increase of DTR was associated with a decrease of 3.92% for VLF, 6.99% for LF, 5.88% for HF, 3.94% for rMSSD and 1.30% for pNN50. Each IQR increase of SDT was associated with a decline of 6.48% for LF, 5.91% for HF, 4.26% for rMSSD and 1.87% for pNN50. Every IQR increase of SDT was associated with a decrease of 4.39% for VLF, 7.67% for LF, 6.52% for HF, 3.22% for SDNN, 2.98% for SDANN, 4.05% for rMSSD, and 1.41% for pNN50. The decrements in HRV associated with temperature variability were more prominent in females. CONCLUSION: Temperature variability on the concurrent day could significantly decrease cardiac autonomic function, especially in females.

Fine particulate matter constituents and heart rate variability: A panel study in Shanghai, China.

BACKGROUND: Short-term exposure to fine particulate matter (PM2.5) has been associated with reduced heart rate variability (HRV), an established indicator of cardiac autonomic function, but it remains uncertain which specific constituents of PM2.5 had key impacts. OBJECTIVE: To examine the short-term associations between various PM2.5 constituents and HRV measures. METHODS: We conducted a retrospective panel study among 78 participants who received repeated 24-h electrocardiogram testing in Shanghai, China from 2015 to 2019. We obtained daily concentrations of 14 main chemical constituents of PM2.5 from a fixed-site monitor. During 3 or 4 rounds of follow-ups, we measured 6 HRV parameters, including 3 frequency-domain parameters (power in very low frequency, low frequency and high frequency) and 3 time-domain parameters (standard deviation of normal-to-normal intervals, root mean square successive difference and percent of adjacent normal R-R intervals with a difference ≥50 msec). We used linear mixed-effects models to analyze the data after controlling for time trends, environmental and individual risk factors. RESULTS: The average daily PM2.5 exposure was 45.8 µg/m3 during the study period. The present-day exposure to PM2.5 had the strongest negative influences on various HRV indicators. These associations attenuated greatly on lag 1 d or lag 2 d. Elemental carbon, organic carbon, nitrate, sulfate, arsenic, cadmium, chromium and nickel were consistently associated with reduced HRV parameters in both single-constituent models and constituent-PM2.5 models. CONCLUSION: Our study highlighted the key roles of traffic-related components of PM2.5 in inhibiting cardiac autonomic function.

Size-fractionated particulate air pollution and myocardial infarction emergency hospitalization in Shanghai, China.

BACKGROUND: Fine particulate matter (PM2.5) air pollution has been associated with increased risks of acute myocardial infarction (AMI), but it remains unknown about the potentially differentiated effects of size-fractionated particulate matter on AMI risk. OBJECTIVE: To identify the specific size ranges that dominate the effects of particulate matter on AMI onset. METHODS: We conducted a time-series study in Shanghai, China from January 2014 to December 2018. We evaluated particle size distribution of 0.01 µm to 2.5 µm from an environmental supersite and AMI emergency hospitalizations from the largest cardiovascular hospital in Shanghai. We used over-dispersed generalized additive models to estimate the associations of size-fractionated particle number concentrations (PNC) with AMI and its types. RESULTS: We identified a total of 4720 AMI emergency hospitalizations. PM2.5 was significantly associated with increased AMI risk on the concurrent day. The associations were significant only for PNC < 0.3 µm. For an IQR increase of PNCs for size ranges 0.01-0.03 µm, 0.03-0.05 µm, 0.05-0.10 µm and 0.10-0.30 µm, AMI hospitalizations increased by 6.68% (95% CI: 2.77%, 10.74%), 6.53% (95% CI: 2.08%, 11.17%), 5.78% (95% CI: 0.92%, 10.88%) and 5.92% (95% CI: 1.31%, 10.74%), respectively. The associations of PNC < 0.05 µm remained significant when adjusting for other air pollutants. There were consistently much stronger associations of particles with ST-segment elevation AMI than those with non-ST-segment elevation AMI. CONCLUSIONS: This epidemiological investigation suggested that ultrafine particles, especially those <0.05 µm, may be mainly responsible for the acute AMI risk induced by PM2.5.

Targeting metabolic flexibility via angiopoietin-like 4 protein sensitizes metastatic cancer cells to chemotherapy drugs.

Overcoming multidrug resistance has always been a major challenge in cancer treatment. Recent evidence suggested epithelial-mesenchymal transition plays a role in MDR, but the mechanism behind this link remains unclear. We found that the expression of multiple ABC transporters was elevated in concordance with an increased drug efflux in cancer cells during EMT. The metastasis-related angiopoietin-like 4 (ANGPTL4) elevates cellular ATP to transcriptionally upregulate ABC transporters expression via the Myc and NF-κB signaling pathways. ANGPTL4 deficiency reduced IC50 of anti-tumor drugs and enhanced apoptosis of cancer cells. In vivo suppression of ANGPTL4 led to higher accumulation of cisplatin-DNA adducts in primary and metastasized tumors, and a reduced metastatic tumor load. ANGPTL4 empowered cancer cells metabolic flexibility during EMT, securing ample cellular energy that fuels multiple ABC transporters to confer EMT-mediated chemoresistance. It suggests that metabolic strategies aimed at suppressing ABC transporters along with energy deprivation of EMT cancer cells may overcome drug resistance.

Angiopoietin-like 4 Mediates Colonic Inflammation by Regulating Chemokine Transcript Stability via Tristetraprolin.

Many gastrointestinal diseases exhibit a protracted and aggravated inflammatory response that can lead to hypercytokinaemia, culminating in extensive tissue damage. Recently, angiopoietin-like 4 (ANGPTL4) has been implicated in many inflammation-associated diseases. However, how ANGPTL4 regulates colonic inflammation remains unclear. Herein, we show that ANGPTL4 deficiency in mice (ANGPTL4-/-) exacerbated colonic inflammation induced by dextran sulfate sodium (DSS) or stearic acid. Microbiota was similar between the two genotypes prior DSS challenge. A microarray gene expression profile of the colon from DSS-treated ANGPTL4-/- mice was enriched for genes involved in leukocyte migration and infiltration, and showed a close association to inflamed ulcerative colitis (UC), whereas the profile from ANGPTL4+/+ littermates resembled that of non-inflamed UC biopsies. Bone marrow transplantation demonstrates the intrinsic role of colonic ANGPTL4 in regulating leukocyte infiltration during DSS-induced inflammation. Using immortalized human colon epithelial cells, we revealed that the ANGPTL4-mediated upregulation of tristetraprolin expression operates through CREB and NF-κB transcription factors, which in turn, regulates the stability of chemokines. Together, our findings suggest that ANGPTL4 protects against acute colonic inflammation and that its absence exacerbates the severity of inflammation. Our findings emphasize the importance of ANGPTL4 as a novel target for therapy in regulating and attenuating inflammation.

Enhanced Photocatalytic Activity of CdS-Decorated TiO2/Carbon Core-Shell Microspheres Derived from Microcrystalline Cellulose.

The fabrication of reusable and biodegradation materials from renewable resources such as cellulose is essential for a sustainable world. The core-shell structured CdS-decorated TiO2/Carbon microspheres (CdS/TiO2/Carbon MS) photocatalyst was synthesized with controlled hydrolysis and a novel sonochemical method. It was prepared by using crosslinked microcrystalline cellulose as the core, tetrabutyl titanate as the titania source and CdS as the photosensitizer. The morphology, chemical structure and properties of the obtained material were characterized by many means. Additionally, the photocatalytic activity of the CdS/TiO2/Carbon MS was evaluated by the photodegradation efficiency of Rhodamine B solution, which reached 95.24% under visible light irradiation. This study demonstrated the excellent photocatalytic performance of CdS/TiO2/Carbon MS, which might have promising applications in environmental treatments.

A comparison of the efficacy of surgical renal denervation and pharmacologic therapies in post-myocardial infarction heart failure.

OBJECTIVE: Although renal denervation (RD) has been shown to be effective in treating post- myocardial Infarction (MI) heart failure (HF) in animal models and clinical trials, its utility as a standalone treatment without traditional drug treatment for post-MI HF still needs to be investigated. METHODS: Rats were randomly assigned into seven experimental groups: N group (control group with no MI and no RD, n = 10), MI group (MI, n = 20), RD group (renal denervation, n = 10), RD-3d+MI group (RD performed three days before MI, n = 15), ß-blocker-3d+MI group (Metoprolol treated three days before MI, n = 15), ACEI-3d+MI group (Perindopril treated three days before MI, n = 15), and ARB-3d+MI group (Losartan treated three days before MI, n = 15). Cardiac function, autonomic nervous system parameters, and neuroendocrine activities were evaluated 8 weeks post MI. RESULTS: Compared to ß-blockers, ACEIs, and ARBs, RD alone provided significantly better cardiac remodeling and function, enhanced water and sodium excretion, and improved autonomic modulation. CONCLUSIONS: In this post-MI HF animal model, surgical RD provides effective autonomic modulation, inhibition of the RAAS, improved cardiac remodeling, and preserved renal function, without affecting normal circulation and cardiopulmonary function in normal rats. Compared to ß-blocker, ACEI, and ARB single-drug therapies, RD alone is more efficacious. These results suggest that RD may be an effective treatment option for HF, especially in patients who have contraindications to drug therapy.

Effect of C/N ratios on the performance of earthworm eco-filter for treatment of synthetics domestic sewage.

PURPOSE: The performances of filter systems that use earthworms and plants, combined with earthworm eco-filter (EE) systems in treating synthetic domestic sewage (SDS) with different C/N ratios, were investigated for a 9-month period. METHODS: The effects of the combination of filters, earthworms, plants, as well as the combination of earthworms and plants on SDS nutrient removal efficiency were separately investigated to select the optimum system for treating SDS. The results of the current study could be used to determine how treatment performance responds to different C/N ratios and to explain and predict the performance of an operating EE system. RESULTS: EE systems with earthworms and plants (EP groups) consistently performed better than the other types of systems (CK, E, and P; that is, without earthworms and without plants, with earthworms and without plants, and without earthworms and with plants, respectively) under all C/N ratios. The highest removal efficiencies of chemical oxygen demand, total nitrogen, total phosphorus, and total organic carbon were achieved under C/N ratios of 6:1, 6:1, 6:1, and 9:1, respectively. The optimum nutrient removal efficiency was achieved at C/N = 6, and the contribution order for nutrient removal was EP > P > E > CK. CONCLUSIONS: Influent C/N ratios, the time of year, and the synergetic effects of earthworm behavior and microorganisms significantly affected nutrient removal efficiencies. Considering the removal of all nutrients, EE systems with plants and earthworms achieved optimum removal effects in July when the influent C/N ratio was controlled at 6. Appropriate control of carbon and nitrogen source concentrations permitted the achievement of optimal nutrient removal effects.

Evaluation of Takayasu arteritis activity by delayed contrast-enhanced magnetic resonance imaging.

BACKGROUND: To measure and assess the disease activity of Takayasu arteritis (TA) quantitatively by magnetic resonance angiography (MRA). METHODS: Twenty-six Chinese TA patients were divided into an active group and an inactive group. All patients underwent delayed contrast-enhanced MRI. The vessels involved were categorized into type A (main branches of aorta and its arch) and type B (secondary or tertiary branches). Three quantitative scores were defined to gauge lumen stenosis, vessel wall thickness, and vessel wall enhancement, and compared between groups and types. RESULTS: The patients in the active group had more stenosis in left subclavian artery than those in the inactive group (14/16, 87.5% vs. 2/10, 20%; p<0.01), and greater vessel wall thickness in left common carotid artery (11/16, 68.75% vs. 1/10, 10%; p<0.01) and left subclavian artery (9/16, 56.25% vs. 0/10, 0%; p<0.01). The differences between active and inactive TA were significant in type A (lumen stenosis: 11.13 ± 6.17 vs. 4.00 ± 4.32; p<0.001; wall thickness: 8.00 ± 5.05 vs. 3.10 ± 3.31; p=0.01; wall enhancement: 6.94 ± 5.34 vs. 2.90 ± 4.36; p=0.05), and pronounced in type A+B (lumen stenosis: 13.31 ± 7.19 vs. 6.30 ± 5.60; p=0.02; wall thickness: 8.50 ± 5.29 vs. 3.40 ± 3.34; p=0.01; wall enhancement: 7.94 ± 6.55 vs. 3.20 ± 4.32, p=0.05, respectively). These three scores were moderately correlated to CRP, platelet count and fibrinogen levels (p<0.05). CONCLUSIONS: The MRI scoring system of lumen stenosis, wall thickness and wall enhancement could be a non-invasive approach to facilitate assessment in TA activity.

Radiographic verification of pedicle screw pilot hole placement in thoracic spine using Kirschner wires versus spiral wires.

OBJECTIVE: To evaluate the feasibility of the pedicle screw pilot holes placement in thoracic spine using the spiral wires as the guide pin. METHODS: The pedicle screw pilot holes were drilled within the center of the pedicle and the lateral and medial pedicle walls were violated in 9 human dried thoracic vertebrae. Kirschner wires or spiral wires were separately placed in the holes, and then the posteroanterior and lateral radiographs were taken. The radiographs were evaluated by 3 experienced spine surgeons and 3 young orthopedists. After radiographs were shown to these observers, they combined the posteroanterior and lateral radiographs in each place and determined whether the pedicle screw pilot hole violated the pedicle cortex or not. The results were analyzed by a statistical software. RESULTS: Sensitivity, specificity and accuracy of the method using spiral wires to detect pedicle pilot hole placement were significantly higher than those of using Kirschner wires. With a true posteroanterior radiograph, the sensitivity, specificity and accuracy of the method using spiral wires approximated or attained 100%. CONCLUSIONS: The method of intrapedicular pilot hole placement verification using spiral wires is effective for guiding the accurate placement of pedicle screws.

Prosthetic replacement in treatment of subcapital femoral neck fractures in the elderly.

OBJECTIVE: To compare the results of femoral head replacement (FHR) and total hip replacement (THR) in treatment of subcapital femoral neck fractures (SFNF). METHODS: Between May 1987 and July 1998, 56 elderly patients (6 5-90 years; average 73.5 years) with SFNF were treated with prosthetic replacement. Six cases were treated with unipolar FHR, 18 cases with Bateman bipolar FHR, and 32 cases with Bateman bipolar THR. All domestic prostheses were installed with cement. RESULTS: There was no significant difference between the 2 groups in operating time and blood transfusion. Forty-nine patients were followed-up for an average of 5 years and 10 months. No wound infection or death was related to surgery. Complications in Group FHR were significantly higher than that i n Group THR. CONCLUSIONS: Since FHR is difficult to fit the bony acetabulum, it is only indicated for senile cases with poor conditions. However, the bi polar THR installed with cement is indicated for most elderly patients. Since th e femoral head and acetabulum can fit each other completely, it is more stable for taking weight-bearing earlier with less complications.