Patient-Level Pooled Analysis of Endovascular Ultrasound Renal Denervation or a Sham Procedure 6 Months After Medication Escalation: The RADIANCE Clinical Trial Program.

BACKGROUND: The randomized, sham-controlled RADIANCE-HTN (A Study of the Recor Medical Paradise System in Clinical Hypertension) SOLO, RADIANCE-HTN TRIO, and RADIANCE II (A Study of the Recor Medical Paradise System in Stage II Hypertension) trials independently met their primary end point of a greater reduction in daytime ambulatory systolic blood pressure (SBP) 2 months after ultrasound renal denervation (uRDN) in patients with hypertension. To characterize the longer-term effectiveness and safety of uRDN versus sham at 6 months, after the blinded addition of antihypertensive treatments (AHTs), we pooled individual patient data across these 3 similarly designed trials. METHODS: Patients with mild to moderate hypertension who were not on AHT or with hypertension resistant to a standardized combination triple AHT were randomized to uRDN (n=293) versus sham (n=213); they were to remain off of added AHT throughout 2 months of follow-up unless specified blood pressure (BP) criteria were exceeded. In each trial, if monthly home BP was ≥135/85 mm Hg from 2 to 5 months, standardized AHT was sequentially added to target home BP <135/85 mm Hg under blinding to initial treatment assignment. Six-month outcomes included baseline- and AHT-adjusted change in daytime ambulatory, home, and office SBP; change in AHT; and safety. Linear mixed regression models using all BP measurements and change in AHT from baseline through 6 months were used. RESULTS: Patients (70% men) were 54.1±9.3 years of age with a baseline daytime ambulatory/home/office SBP of 150.5±9.8/151.0±12.4/155.5±14.4 mm Hg, respectively. From 2 to 6 months, BP decreased in both groups with AHT titration, but fewer uRDN patients were prescribed AHT (P=0.004), and fewer additional AHT were prescribed to uRDN patients versus sham patients (P=0.001). Whereas the unadjusted between-group difference in daytime ambulatory SBP was similar at 6 months, the baseline and medication-adjusted between-group difference at 6 months was -3.0 mm Hg (95% CI, -5.7, -0.2; P=0.033), in favor of uRDN+AHT. For home and office SBP, the adjusted between-group differences in favor of uRDN+AHT over 6 months were -5.4 mm Hg (-6.8, -4.0; P<0.001) and -5.2 mm Hg (-7.1, -3.3; P<0.001), respectively. There was no heterogeneity between trials. Safety outcomes were few and did not differ between groups. CONCLUSIONS: This individual patient-data analysis of 506 patients included in the RADIANCE trials demonstrates the maintenance of BP-lowering efficacy of uRDN versus sham at 6 months, with fewer added AHTs. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifiers: NCT02649426 and NCT03614260.

Incidence, treatment and outcomes of coronary artery dissection during percutaneous coronary intervention.

BACKGROUND: Coronary artery dissection is a feared and potentially life-threatening complication of percutaneous coronary intervention (PCI). METHODS: We examined the clinical, angiographic, and procedural characteristics, and outcomes of coronary dissection at a tertiary care institution. RESULTS: Between 2014 and 2019, unplanned coronary dissection occurred in 141 of 10,278 PCIs (1.4%). Median patient age was 68 (60, 78) years, 68% were men, and 83% had hypertension. The prevalence of diabetes (29%), and prior PCI (37%) was high. Most target vessels were significantly diseased: 48% had moderate/severe tortuosity and 62% had moderate/severe calcification. The most common cause of dissection was guidewire advancement (30%), followed by stenting (22%), balloon angioplasty (20%), and guide-catheter engagement (18%). TIMI flow was 0 in 33% and 1-2 in 41% of cases. Intravascular imaging was used in 17% of the cases. Stenting was used to treat the dissection in 73% of patients. There was no consequence of dissection in 43% of patients. Technical and procedural success was 65% and 55%, respectively. In-hospital major adverse cardiovascular events occurred in 23% of patients: 13 (9%) had an acute myocardial infarction (MI), 3 (2%) had emergency coronary artery bypass graft surgery, and 10 (7%) died. During a mean follow up of 1612 days, 28 (20%) patients died, and the rate of target lesion revascularization was 11.3% (n=16). CONCLUSION: Coronary artery dissection is an infrequent complication of PCI, but is associated with adverse clinical outcomes, such as death and acute MI.

Impact of inflammation and anti-inflammatory modalities on diabetic cardiomyopathy healing: From fundamental research to therapy.

Diabetic cardiomyopathy (DCM) is a prevalent cardiovascular complication of diabetes mellitus, characterized by high morbidity and mortality rates worldwide. However, treatment options for DCM remain limited. For decades, a substantial body of evidence has suggested that the inflammatory response plays a pivotal role in the development and progression of DCM. Notably, DCM is closely associated with alterations in inflammatory cells, exerting direct effects on major resident cells such as cardiomyocytes, vascular endothelial cells, and fibroblasts. These cellular changes subsequently contribute to the development of DCM. This article comprehensively analyzes cellular, animal, and human studies to summarize the latest insights into the impact of inflammation on DCM. Furthermore, the potential therapeutic effects of current anti-inflammatory drugs in the management of DCM are also taken into consideration. The ultimate goal of this work is to consolidate the existing literature on the inflammatory processes underlying DCM, providing clinicians with the necessary knowledge and tools to adopt a more efficient and evidence-based approach to managing this condition.

Effect of soluble phosphate and bentonite amendments on lead and cadmium bioavailability and bioaccessibility in a contaminated soil.

Effect of commonly used heavy metal immobilizing agents on risks of soil heavy metals has not been well investigated. In this work, a contaminated acidic soil (total Cd = 8.05, total Pb = 261 mg kg-1) was amended with soluble phosphate (P: 160 mg kg-1) and bentonite (3 g kg-1) and incubated for 360 d. The soil was then added to mouse feed at 1:9 soil: feed ratio (weight) and fed to mouse for 10 days, after which the liver, kidney and bone Pb and Cd concentrations were measured. The amended soils were extracted with SBRC and PBET to assay bioaccessibility, and extracted with DTPA to assess the environmental availability. The amendments did not affect the DTPA-Pb/Cd significantly (p > 0.05), while the Cd bioaccessibility in the gastric phase of the SBRC assay was reduced from 90.0 to 20.4 % for the bentonite amended treatment (p < 0.05). Kidney Pb and Cd concentrations of the mice fed with feed containing phosphate spiked soil was 80.2 and 66.0 % lower than the control mice fed with unamended soil (CK), respectively. Significant linear correlations were found between DTPA-extractable concentration and kidney concentrations for Pb/Cd. The effect of amendment on Pb/Cd bioavailability differed between the results calculated with different endpoints. The phosphate amendment resulted in 82.7 and 34.3 % lower Pb RBA compared with the unamended soil calculated with kidney and kidney+liver+bone Pb concentrations, respectively, and 68.8 and 49.7 % lower Cd RBA than the control with kidney and kidney+liver concentrations, respectively. However, no significant effect was observed with both amendments when the RBA was calculated with liver or bone Pb/Cd concentrations, or on Pb RBA with kidney, liver or bone metal concentrations. Results indicate the complex effect of amendments on organ, tissue and overall health risk of soil Pb/Cd to animal/human.

Scalable graphene sensor array for real-time toxins monitoring in flowing water.

Risk management for drinking water often requires continuous monitoring of various toxins in flowing water. While they can be readily integrated with existing water infrastructure, two-dimensional (2D) electronic sensors often suffer from device-to-device variations due to the lack of an effective strategy for identifying faulty devices from preselected uniform devices based on electronic properties alone, resulting in sensor inaccuracy and thus slowing down their real-world applications. Here, we report the combination of wet transfer, impedance and noise measurements, and machine learning to facilitate the scalable nanofabrication of graphene-based field-effect transistor (GFET) sensor arrays and the efficient identification of faulty devices. Our sensors were able to perform real-time detection of heavy-metal ions (lead and mercury) and E. coli bacteria simultaneously in flowing tap water. This study offers a reliable quality control protocol to increase the potential of electronic sensors for monitoring pollutants in flowing water.

Cadmium and lead bioavailability to poultry fed with contaminated soil-spiked feed.

Geophagy is common for free-range chickens, however, the relative bioavailability (RBA) of heavy metals in contaminated soils consumed by chickens has not fully investigated. In this work, chickens were fed diets increasingly spiked with a contaminated soil (Cd = 105, Pb = 4840 mg kg-1; 3, 5, 10, 20 and 30 % of overall feed by weight), or Cd/Pb reagent spikes (from CdCl2 or Pb(Ac)2), for 23 d. After the study period, chicken liver, kidney, femur and gizzard samples were analyzed for Cd and Pb concentrations, and organ/tissue metal concentrations were used to calculate Cd and Pb RBA. Linear dose response curves (DRCs) were established for both Cd/Pb reagents-spiked and soil-spiked treatments. Femur Cd concentrations of soil-spiked treatments were two times of Cd-spiked treatments with similar feed Cd levels, while feed spiked with Cd or Pb also resulted in elevated Pb or Cd concentrations in some organ/tissues. Metal RBA was calculated using three different methods. Most Cd and Pb RBA values were in the range 50-70 %, with the chicken gizzard as a potential endpoint for bioaccessible Cd and Pb. Cadmium and Pb bioavailability values can help with more precise estimation of Cd and Pb accumulation in chicken following heavy metal-contaminated soil ingestion, with overall results helping to protect human health.

Immobilization of Cd by mercapto-palygorskite in typical calcareous and acidic soil aggregates: Performance and differences.

The microscale spatial heterogeneity and complexity of soil aggregates affect the properties and distribution of heavy metals (HMs). It has been confirmed that amendments can alter the distribution of Cd in soil aggregates. However, whether the Cd immobilization effect of amendments varies across soil aggregate levels remains unknown. In this study, soil classification and culture experiments were combined to explore the effects of mercapto-palygorskite (MEP) on Cd immobilization in soil aggregates of different particle sizes. The results showed that a 0.05-0.2% MEP application decreased soil available Cd by 53.8-71.62% and 23.49-36.71% in calcareous and acidic soils, respectively. The Cd immobilization efficiency of MEP in calcareous soil aggregates was in the following order: micro-aggregates (66.42-80.19%) > bulk soil (53.78-71.62%) > macro-aggregates (44.00-67.51%), while the efficiency in acidic soil aggregates was inconsistent. In MEP-treated calcareous soil, the percentage change in Cd speciation in micro-aggregates were higher than that in macro-aggregates, whereas there was no significant difference in Cd speciation between the four acidic soil aggregates. Mercapto-palygorskite addition in micro-aggregates of calcareous soil increased the available Fe and Mn concentrations by 20.98-47.10% and 17.98-32.66%, respectively. Mercapto-palygorskite had no effect on soil pH, EC, CEC, and DOC values, while the difference in soil properties between the four particle sizes was the main influencing factor of MEP treatments on Cd in calcareous soil. The effects of MEP on HMs varied across soil aggregates and soil types, but had strong specificity and selectivity for Cd immobilization. This study illustrates the influence of soil aggregates on Cd immobilization using MEP, which can be used to guide the remediation of Cd-contaminated calcareous and acidic soils.

Endovascular Ultrasound Renal Denervation to Treat Hypertension: The RADIANCE II Randomized Clinical Trial.

Importance: Two initial sham-controlled trials demonstrated that ultrasound renal denervation decreases blood pressure (BP) in patients with mild to moderate hypertension and hypertension that is resistant to treatment. Objective: To study the efficacy and safety of ultrasound renal denervation without the confounding influence of antihypertensive medications in patients with hypertension. Design, Setting, and Participants: Sham-controlled, randomized clinical trial with patients and outcome assessors blinded to treatment assignment that was conducted between January 14, 2019, and March 25, 2022, at 37 centers in the US and 24 centers in Europe, with randomization stratified by center. Patients aged 18 years to 75 years with hypertension (seated office systolic BP [SBP] ≥140 mm Hg and diastolic BP [DBP] ≥90 mm Hg despite taking up to 2 antihypertensive medications) were eligible if they had an ambulatory SBP/DBP of 135/85 mm Hg or greater and an SBP/DBP less than 170/105 mm Hg after a 4-week washout of their medications. Patients with an estimated glomerular filtration rate of 40 mL/min/1.73 m2 or greater and with suitable renal artery anatomy were randomized 2:1 to undergo ultrasound renal denervation or a sham procedure. Patients were to abstain from antihypertensive medications until the 2-month follow-up unless prespecified BP criteria were exceeded and were associated with clinical symptoms. Interventions: Ultrasound renal denervation vs a sham procedure. Main Outcomes and Measures: The primary efficacy outcome was the mean change in daytime ambulatory SBP at 2 months. The primary safety composite outcome of major adverse events included death, kidney failure, and major embolic, vascular, cardiovascular, cerebrovascular, and hypertensive events at 30 days and renal artery stenosis greater than 70% detected at 6 months. The secondary outcomes included mean change in 24-hour ambulatory SBP, home SBP, office SBP, and all DBP parameters at 2 months. Results: Among 1038 eligible patients, 150 were randomized to ultrasound renal denervation and 74 to a sham procedure (mean age, 55 years [SD, 9.3 years]; 28.6% female; and 16.1% self-identified as Black or African American). The reduction in daytime ambulatory SBP was greater with ultrasound renal denervation (mean, -7.9 mm Hg [SD, 11.6 mm Hg]) vs the sham procedure (mean, -1.8 mm Hg [SD, 9.5 mm Hg]) (baseline-adjusted between-group difference, -6.3 mm Hg [95% CI, -9.3 to -3.2 mm Hg], P < .001), with a consistent effect of ultrasound renal denervation throughout the 24-hour circadian cycle. Among 7 secondary BP outcomes, 6 were significantly improved with ultrasound renal denervation vs the sham procedure. No major adverse events were reported in either group. Conclusions and Relevance: In patients with hypertension, ultrasound renal denervation reduced daytime ambulatory SBP at 2 months in the absence of antihypertensive medications vs a sham procedure without postprocedural major adverse events. Trial Registration: ClinicalTrials.gov Identifier: NCT03614260.

Patient-Level Pooled Analysis of Ultrasound Renal Denervation in the Sham-Controlled RADIANCE II, RADIANCE-HTN SOLO, and RADIANCE-HTN TRIO Trials.

Importance: Ultrasound renal denervation (uRDN) was shown to lower blood pressure (BP) in patients with uncontrolled hypertension (HTN). Establishing the magnitude and consistency of the uRDN effect across the HTN spectrum is clinically important. Objective: To characterize the effectiveness and safety of uRDN vs a sham procedure from individual patient-level pooled data across uRDN trials including either patients with mild to moderate HTN on a background of no medications or with HTN resistant to standardized triple-combination therapy. Data Sources: A Study of the ReCor Medical Paradise System in Clinical Hypertension (RADIANCE-HTN SOLO and TRIO) and A Study of the ReCor Medical Paradise System in Stage II Hypertension (RADIANCE II) trials. Study Selection: Trials with similar designs, standardized operational implementation (medication standardization and blinding of both patients and physicians to treatment assignment), and follow-up. Data Extraction and Synthesis: Pooled analysis using individual patient-level data using linear regression models to compare uRDN with sham across the trials. Main Outcomes and Measures: The primary outcome was baseline-adjusted change in 2-month daytime ambulatory systolic BP (dASBP) between groups. Results: A total of 506 patients were randomized in the 3 studies (uRDN, 293; sham, 213; mean [SD] age, 54.1 [9.3]; 354 male [70.0%]). After a 1-month medication stabilization period, dASBP was similar between the groups (mean [SD], uRDN, 150.3 [9.2] mm Hg; sham, 150.8 [10.5] mm Hg). At 2 months, dASBP decreased by 8.5 mm Hg to mean (SD) 141.8 (13.8) mm Hg among patients treated with uRDN and by 2.9 mm Hg to 147.9 (14.6) mm Hg among patients treated with a sham procedure (mean difference, -5.9; 95% CI, -8.1 to -3.8 mm Hg; P < .001 in favor of uRDN). BP decreases from baseline with uRDN vs sham were consistent across trials and across BP parameters (office SBP: -10.4 mm Hg vs -3.4 mm Hg; mean difference, -6.4 mm Hg; 95% CI, -9.1 to -3.6 mm Hg; home SBP: -8.4 mm Hg vs -1.4 mm Hg; mean difference, -6.8 mm Hg; 95% CI, -8.7 to -4.9 mm Hg, respectively). The BP reductions with uRDN vs sham were consistent across prespecified subgroups. Independent predictors of a larger BP response to uRDN were higher baseline BP and heart rate and the presence of orthostatic hypertension. No differences in early safety end points were observed between groups. Conclusions and Relevance: Results of this patient-level pooled analysis suggest that BP reductions with uRDN were consistent across HTN severity in sham-controlled trials designed with a 2-month primary end point to standardize medications across randomized groups. Trial Registration: ClinicalTrials.gov Identifier: NCT02649426 and NCT03614260.

Heavy metal distribution in wheat plant components following foliar Cd application.

Atmospheric deposition of Cd, from anthropogenic activities, can be directly deposited onto and absorbed into wheat plants, yet, how foliar absorbed Cd is translocated in wheat plants is not well understood. A pot experiment investigated foliar Cd application on the accumulation and distribution of heavy metals in various wheat parts. Wheat was grown in a Cd/heavy metal contaminated soil, and from grain heading to the filling stage, 0, 10, 20, 30 and 40 mg kg-1 Cd solution was sprayed repeatedly on leaves (grain heads were covered). Foliar Cd application had no effect on grain yield and Cd concentration (3.01-3.51 mg kg-1 for all treatments), while increased flag leaf blade and sheath Cd concentrations by 1.06-2.77 and 0.00-0.66 times, respectively. Cadmium concentration in the center of the peduncle, from the 40 mg kg-1 Cd solution treatment, was 1.41 times that of the control (10.3 vs 7.30 mg kg-1). Foliar Cd application also increased Cd accumulation (concentration × mass) of the flag leaf blade and sheath. Rachis and grain Pb concentrations were reduced, while stem Pb concentration was increased by Cd application. Cadmium application negatively affected whole plant Ni accumulation and concentration of certain wheat parts; Ni absorption inhibition may have occurred in roots via the downward transport of Cd. Overall results implied that the predominant portion of foliar applied Cd was retained in leaves, while lesser portions migrated to peduncle or root and affected the absorption/distribution of other metals in wheat plants. These results are important for further discerning the mechanism of wheat grain Cd accumulation, especially when grain is raised in areas where atmospheric deposition of Cd (e.g., near smelting facilities) is an issue from an environmental and human health perspective.

Accumulation and speciation of arsenic in Eisenia fetida in sodium arsenite spiked soils - A dynamic interaction between soil and earthworms.

Arsenic (As) is a toxic metalloid that is a significant global pollutant of the environment and a persistent bioaccumulation carcinogen. Earthworms are frequently employed as sentinel organisms to investigate the bioavailability of As in contaminated soils. However, the process of As accumulation in earthworms and the mechanism of transformation of As species in their bodies are not well understood. The accumulation of As and variation of As species in the earthworms (Eisenia fetida) exposed to sodium arsenite (0, 20, and 80 mg kg-1 As) were investigated in this study. The total As concentration of earthworms in the three treatments at various sample times was dose-dependent on soil As content. After 56 days of exposure, the high concentration treatment had the highest total As content (772 ± 21 mg kg-1) in earthworms, followed by the low concentration treatment (579 ± 42 mg kg-1) and control (31 ± 1 mg kg-1). During 56 days, the proportion of trivalent As in earthworms increased from 70% to more than 90%, while pentavalent As decreased by 11-18%. On day 28, the sum of the four organic As species reached a maximum (<1%). Changes in soil As species and an increase in bioavailable As cause earthworms to accumulate more As. The total As in soil after 56 days of exposure was 9.51 ± 0.50, 25.6 ± 0.60, and 82.8 ± 0.28 mg kg-1, which was not significantly different from the total As in soil before the experiment. These findings are useful in assessing the risk of earthworm exposure to sodium arsenite in the soil.

Soil addition of MnSO4 reduces wheat Cd accumulation by simultaneously increasing labile Mn and decreasing labile Cd concentrations in calcareous soil: A two-year pot study.

Cadmium (Cd) pollution of wheat fields is a serious environmental and health problem that warrants attention. Manganese (Mn)-containing materials are considered effective for inhibiting Cd accumulation in Cd-contaminated acidic soils. However, information on the long-term remediation effects of Mn fertilizers on Cd accumulation in wheat and on the microbial community in calcareous soils remain limited. Here, a two-year pot experiment was conducted to assess the performance of 0.05-0.2% MnSO4 addition in Cd-contaminated calcareous soils (total Cd concentration: 3.65 mg/kg) on Cd accumulation in wheat as well as on the soil bacterial community. The formation of Mn oxides and transformation of exchangeable Cd to stable Cd fractions confirmed that the application of MnSO4 significantly decreased CaCl2-extractable Cd concentrations in soil (0-47.08%). In addition, MnSO4 addition improved the antagonistic effect of Cd and Mn ions in the wheat rhizosphere by increasing the available Mn concentration in the soil (1.04-3.52 times), thereby significantly reducing wheat Cd accumulation by 24.66-54.70%. Notably, the addition of MnSO4 did not affect the richness and diversity (P > 0.05) but altered the composition and function of bacterial communities, especially those involved in metabolism and genetic information processing. Importantly, the effects of MnSO4 on Cd immobilization in soil (10.66-47.08%) and the inhibition of Cd accumulation in wheat (12.13-54.30%) can last for two years after one addition. Furthermore, the maximum decrease in Cd concentration in grains was found in the low-Cd wheat cultivar, with values of 31.39-54.70% and 19.94-54.30% in the first and second years, respectively. Based on the present findings, the combination of MnSO4 with a low-Cd wheat cultivar is effective for the safe utilization of Cd-contaminated calcareous soils.

Three-Year Outcomes After Bifurcation Stenting With Zotarolimus-Eluting Stents: Final Results From the RESOLUTE ONYX Postapproval Study.

Background: Bifurcation represents a challenging lesion subset for percutaneous coronary intervention. Methods: In this prospective study of the Resolute Onyx zotarolimus-eluting stent (ZES), patients with a single bifurcation target lesion who underwent planned treatment using a provisional stenting technique were enrolled at 25 centers in the United States and Europe. The primary end point was target-vessel failure (TVF) at 1 year, and follow-up was performed through 3 years. Results: A total of 205 patients were enrolled. Mean age was 66.6 ± 10.7 years, 21.5% of patients were female, and diabetes mellitus was present in 30.2%. A provisional approach with a single stent was performed in 96.6% of patients. The rate of TVF at 1 year was 7.4%, fulfilling the prespecified performance criterion (upper 1-sided 95% CI of 11.1%, compared with the performance goal of 24.5%). At 3-year follow-up, the rate of TVF was 12.1%, the rate of clinically driven target-lesion revascularization was 6.0%, and there were no episodes of stent thrombosis related to the target lesion. Event rates were consistent among the cohort of patients with angiographic core laboratory-confirmed bifurcation lesions. Conclusions: In this prospective, multicenter study, bifurcation lesion treatment with Resolute Onyx ZES using a planned provisional stent approach was associated with favorable clinical outcomes through 3 years. These results support the longer-term safety and effectiveness of Resolute Onyx ZES to treat bifurcation lesions that are amenable to a planned provisional stenting technique.

Iatrogenic aortic dissection of the descending aorta after percutaneous coronary intervention.

Aortic dissection is a rare and potentially fatal complication of coronary angiography. We report a case of a woman in her late 80s who underwent a left femoral approach coronary angiogram for evaluation of a transcatheter aortic valve replacement (TAVR). Following the procedure, she had a cardiac arrest and was found to have a descending aortic dissection on transoesophageal echocardiogram. Autopsy showed an acute intimal tear of the descending aorta, most likely related to catheter manipulation. Patients undergoing evaluation for TAVR, who tend to be elderly with concomitant atherosclerosis, are at risk for complications following cardiac catheterisation including aortic dissection.

Outcomes and challenges of the provisional stenting technique: Insights from the PROGRESS-BIFURCATION registry.

BACKGROUND: Provisional stenting is the most commonly used coronary bifurcation stenting strategy. METHODS: We examined the clinical and angiographic characteristics, challenges encountered, and procedural outcomes with the provisional bifurcation stenting strategy in the Prospective Global Registry of Percutaneous Coronary Intervention (PCI) in Bifurcation Lesions (PROGRESS-BIFURCATION, NCT05100992). RESULTS: Provisional stenting was used in 334 of 430 bifurcation interventions (78%). Technical success was lower (95% vs. 100%, p = 0.017) in provisional, but procedural success (90% vs. 95%, p = 0.095) and incidence of in-hospital major adverse cardiovascular events were similar (5% vs. 5%, p = 0.945) compared with two-stent strategies. Provisional was less often preferred in left main/left anterior descending involvement (47% vs. 73%, p < 0.001). Provisional stenting cases had smaller side branch (SB) diameter (2.4 ± 0.5 vs. 2.7 ± 0.6 mm, p < 0.001), shorter SB lesion length (5 [3-8] vs. 10 [5-10] mm, p < 0.001), less SB diameter stenosis (46 ± 35 vs. 81 ± 20%, p < 0.001), and were less likely to be Medina 1,1,1 (34% vs. 73%, p < 0.001). PCI challenges were less common (30% vs. 58%, p < 0.001) with provisional stenting: (1) rewiring difficulty (43%) that was overcome with use of a different wire (74%) or microcatheter (46%); (2) inability to deliver a stent (22%) or balloon (9%) that was overcome with use of a smaller balloon (88%), rewiring (25%), or increased support/microcatheter (25%). CONCLUSIONS: Provisional bifurcation stenting was more often performed in distal lesions with less SB involvement and had lower technical success, but similar procedural success and complications compared with two-stent strategies.

Durability of blood pressure reduction after ultrasound renal denervation: three-year follow-up of the treatment arm of the randomised RADIANCE-HTN SOLO trial.

BACKGROUND: While the blood pressure (BP)-lowering effect of renal denervation (RDN) has been established, long-term durability is a key prerequisite for a broader clinical implementation. AIMS: Our aims were to assess the long-term durability of the office BP (OBP)-lowering efficacy, antihypertensive medication (AHM) use, and safety of ultrasound RDN (uRDN). METHODS: Four weeks after withdrawal of AHM, patients with untreated daytime ambulatory BP ≥135/85 mmHg and <170/105 mmHg were randomised to uRDN (n=74) or sham (n=72) in the RADIANCE-HTN SOLO trial. Initiation of AHM was encouraged for home BP >135/85 mmHg following primary endpoint ascertainment at 2 months. Patients and physicians were unblinded at 6 months.  Results: Fifty-one of 74 patients (age: 53.9±11 years; 67% men) originally randomised to uRDN completed the 36-month follow-up. Initial screening OBP upon study entry was 145/92±14/10 mmHg on a mean of 1.2 AHM (range: 0-2.0). Baseline OBP after AHM washout was 154/99±13/8 mmHg. At 36 months, patients were on an average of 1.3 AHM (range: 0-3.0) with 8 patients on no AHM. OBP decreased by 18/11±15/9 mmHg from baseline to 36 months (p<0.001 for both). Overall, OBP control (<140/90 mmHg) improved from 29.4% at screening to 45.1% at 36 months (p=0.059). For patients uncontrolled at screening (n=36), systolic OBP decreased by 10.8 mmHg (p<0.001) at 36 months on similar AHM (p=0.158). CONCLUSIONS: The safety and effectiveness of uRDN was durable to 36 months, with reduced OBP and improved OBP control despite a similar starting medication burden. No new uRDN-related long-term safety concerns were identified.

Bioaccessibility, source and human health risk of Pb, Cd, Cu and Zn in windowsill dusts from an area affected by long-term Pb smelting.

Non-ferrous metal smelting results in heterogenous spatial distribution of potentially toxic metals (PTM) near smelters. In this work, windowsill dusts were collected from smelting (SA) and urban (UJ) sub-areas of Jiyuan (a city affected by >70 years of Pb smelting) to investigate PTM source and bioaccessibility. The <10 µm fraction of dusts were analyzed for total and bioaccessible Pb, Cd, Cu and Zn concentrations; bioaccessibility was analyzed by a three-stage assay (i.e., lung phase, gastric phase and gastrointestinal phase) using artificial lysosomal fluid (ALF, L phase) followed by simulated gastric and gastrointestinal fluids (G and GI phases). This assay mimicked the movement of particles phagocytosed by alveolar macrophages in the respiratory system, then transported up the oropharynx and subsequently swallowed and transported into the digestive system. Zinc had greater bioaccessible concentrations in L and GI phases than other metals, and the mean L phase bioaccessible PTM concentrations in SA were greater than in UJ. The mean L + GI phase bioaccessible concentrations of Pb, Cd, Cu and Zn in SA were 280, 79, 124 and 1458 mg kg-1, while those in UJ were 215, 54, 116 and 598 mg kg-1, respectively. The L phase extracted 87.7 to 98.8 % of PTM within the L + GI assay. Lead had a lower L + GI bioaccessibility than Cd, Cu and Zn (70-76 % vs. 82-92 %). Higher tolerable Cd carcinogenic risks based on bioaccessibility were found in SA sub-area than in UJ while no carcinogenic or non-carcinogenic risk was found for other metals. Lead isotopic ratios indicated that both Pb ore and smelting bottom ash contributed to dust Pb accumulation in SA, while coal burning, lead ore, Pb smelting bottom ash and diesel engine exhaust contributed to dust Pb accumulation in UJ. Overall, results indicated heterogenous distribution of PTM source and bioaccessibility in the vicinity of Pb smelters.

Incidence, Treatment, and Outcomes of Coronary Artery Perforation During Percutaneous Coronary Intervention.

OBJECTIVES: To examine the incidence, treatment and outcomes of perforation during percutaneous coronary intervention (PCI). BACKGROUND: Coronary perforation is a potentially life-threatening PCI complication. METHODS: We examined the clinical, angiographic, and procedural characteristics, management, and outcomes of coronary perforation at a tertiary care institution. RESULTS: Between 2014 and 2019, perforation occurred in 70 of 10,278 PCIs (0.7%). Patient age was 71 ± 12 years, 66% were men, and 30% had prior coronary artery bypass graft surgery. Among perforation cases, the prevalence of chronic total occlusions was 33%, moderate/severe calcification was 66% and moderate/severe tortuosity was 41%. The frequency of Ellis class 1, 2, and 3 perforations was 14%, 50%, and 36%, respectively. Most (n = 51; 73%) were large vessel perforations, 16 (23%) were distal vessel perforations and 3 (4%) were collateral vessel perforations (1 septal and 2 epicardial). Hypotension occurred in 26%, pericardial effusion in 36% and tamponade in 13%; 47% of perforations did not have clinical consequences. Perforations were most often treated with prolonged balloon inflation (63%), reversal of anticoagulation (39%), and covered stent implantation (33%). Technical and procedural success were 73% and 60%, respectively, and major periprocedural adverse cardiac events occurred in 21% of the patients. Three patients (4%) required emergent CABG surgery and four (6%) died. CONCLUSIONS: Coronary perforation is an infrequent complication of PCI. Most perforations are large vessel perforations and often require further intervention. The incidence of death or emergent cardiac surgery is low.

Remote Floating-Gate Field-Effect Transistor with 2-Dimensional Reduced Graphene Oxide Sensing Layer for Reliable Detection of SARS-CoV-2 Spike Proteins.

Despite intensive research of nanomaterials-based field-effect transistors (FETs) as a rapid diagnostic tool, it remains to be seen for FET sensors to be used for clinical applications due to a lack of stability, reliability, reproducibility, and scalability for mass production. Herein, we propose a remote floating-gate (RFG) FET configuration to eliminate device-to-device variations of two-dimensional reduced graphene oxide (rGO) sensing surfaces and most of the instability at the solution interface. Also, critical mechanistic factors behind the electrochemical instability of rGO such as severe drift and hysteresis were identified through extensive studies on rGO-solution interfaces varied by rGO thickness, coverage, and reduction temperature. rGO surfaces in our RFGFET structure displayed a Nernstian response of 54 mV/pH (from pH 2 to 11) with a 90% yield (9 samples out of total 10), coefficient of variation (CV) < 3%, and a low drift rate of 2%, all of which were calculated from the absolute measurement values. As proof-of-concept, we demonstrated highly reliable, reproducible, and label-free detection of spike proteins of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in a saliva-relevant media with concentrations ranging from 500 fg/mL to 5 µg/mL, with an R2 value of 0.984 and CV < 3%, and a guaranteed limit of detection at a few pg/mL. Taken together, this new platform may have an immense effect on positioning FET bioelectronics in a clinical setting for detecting SARS-CoV-2.