Inhibition of the angiotensin II type 2 receptor AT2R is a novel therapeutic strategy for glioblastoma.

Glioblastoma (GBM) is an aggressive malignant primary brain tumor with limited therapeutic options. We show that the angiotensin II (AngII) type 2 receptor (AT2R) is a therapeutic target for GBM and that AngII, endogenously produced in GBM cells, promotes proliferation through AT2R. We repurposed EMA401, an AT2R antagonist originally developed as a peripherally restricted analgesic, for GBM and showed that it inhibits the proliferation of AT2R-expressing GBM spheroids and blocks their invasiveness and angiogenic capacity. The crystal structure of AT2R bound to EMA401 was determined and revealed the receptor to be in an active-like conformation with helix-VIII blocking G-protein or ß-arrestin recruitment. The architecture and interactions of EMA401 in AT2R differ drastically from complexes of AT2R with other relevant compounds. To enhance central nervous system (CNS) penetration of EMA401, we exploited the crystal structure to design an angiopep-2-tethered EMA401 derivative, A3E. A3E exhibited enhanced CNS penetration, leading to reduced tumor volume, inhibition of proliferation, and increased levels of apoptosis in an orthotopic xenograft model of GBM.

PI3K signaling promotes formation of lipid-laden foamy macrophages at the spinal cord injury site.

After spinal cord injury (SCI), infiltrating macrophages undergo excessive phagocytosis of myelin and cellular debris, forming lipid-laden foamy macrophages. To understand their role in the cellular pathology of SCI, investigation of the foamy macrophage phenotype in vitro revealed a pro-inflammatory profile, increased reactive oxygen species (ROS) production, and mitochondrial dysfunction. Bioinformatic analysis identified PI3K as a regulator of inflammation in foamy macrophages, and inhibition of this pathway decreased their lipid content, inflammatory cytokines, and ROS production. Macrophage-specific inhibition of PI3K using liposomes significantly decreased foamy macrophages at the injury site after a mid-thoracic contusive SCI in mice. RNA sequencing and in vitro analysis of foamy macrophages revealed increased autophagy and decreased phagocytosis after PI3K inhibition as potential mechanisms for reduced lipid accumulation. Together, our data suggest that the formation of pro-inflammatory foamy macrophages after SCI is due to the activation of PI3K signaling, which increases phagocytosis and decreases autophagy.

Retrograde chronic total occlusion percutaneous coronary intervention via ipsilateral collaterals.

BACKGROUND: There is limited data on retrograde chronic total occlusion (CTO) percutaneous coronary intervention (PCI) via ipsilateral epicardial collaterals (IEC). AIMS: To compare the clinical and angiographic characteristics, and outcomes of retrograde CTO PCI via IEC versus other collaterals in a large multicenter registry. METHODS: Observational cohort study from the Prospective Global registry for the study of Chronic Total Occlusion Intervention (PROGRESS-CTO). RESULTS: Of 4466 retrograde cases performed between 2012 and 2023, crossing through IEC was attempted in 191 (4.3%) cases with 50% wiring success. The most common target vessel in the IEC group was the left circumflex (50%), in comparison to other retrograde cases, where the right coronary artery was most common (70%). The Japanese CTO score was similar between the two groups (3.13 ± 1.23 vs. 3.06 ± 1.06, p = 0.456); however, the IEC group had a higher Prospective Global Registry for the Study of Chronic Total Occlusion Intervention (PROGRESS-CTO) score (1.95 ± 1.02 vs. 1.27 ± 0.92, p < 0.0001). The most used IEC guidewire was the SUOH 03 (39%), and the most frequently used microcatheter was the Caravel (43%). Dual injection was less common in IEC cases (66% vs. 89%, p < 0.0001). Technical (76% vs. 79%, p = 0.317) and procedural success rates (74% vs. 79%, p = 0.281) were not different between the two groups. However, IEC cases had a higher procedural complications rate (25.8% vs. 16.4%, p = 0.0008), including perforations (17.3% vs. 9.0%, p = 0.0001), pericardiocentesis (3.1% vs. 1.2%, p = 0.018), and dissection/thrombus of the donor vessel (3.7% vs. 1.2%, p = 0.002). CONCLUSION: The use of IEC for retrograde CTO PCI was associated with similar technical and procedural success rates when compared with other retrograde cases, but higher incidence of periprocedural complications.

Validation of the BCIS CHIP Score in chronic total occlusion percutaneous coronary intervention.

BACKGROUND: The complex high-risk indicated percutaneous coronary intervention (CHIP) score is a tool developed using the British Cardiovascular Intervention Society (BCIS) database to define CHIP cases and predict in-hospital major adverse cardiac or cerebrovascular events (MACCE). AIM: To assess the validity of the CHIP score in chronic total occlusion (CTO) percutaneous coronary intervention (PCI). METHODS: We evaluated the performance of the CHIP score on 8341 CTO PCIs from the Prospective Global Registry for the Study of Chronic Total Occlusion Intervention (PROGRESS-CTO) performed at 44 centers between 2012 and 2023. RESULTS: In our cohort, 7.8% (n = 647) of patients had a CHIP score of 0, 50.2% (n = 4192) had a CHIP score of 1-2, 26.2% (n = 2187) had a CHIP score of 3-4, 11.7% (n = 972) had a CHIP score of 5-6, 3.3% (n = 276) had a CHIP score of 7-8, and 0.8% (n = 67) had a CHIP score of 9+. The incidence of MACCE for a CHIP score of 0 was 0.6%, reaching as high as 8.7% for a CHIP score of 9+, confirming that a higher CHIP score is associated with a higher risk of MACCE. The estimated increase in the risk of MACCE per one score unit increase was 100% (95% confidence interval [CI]: 65%-141%). The AUC of the CHIP score model for predicting MACCE in our cohort was 0.63 (95% CI: 0.58-0.67). There was a positive correlation between the CHIP score and the PROGRESS-CTO MACE score (Spearman's correlation: 0.37; 95% CI: 0.35-0.39; p < 0.001). CONCLUSIONS: The CHIP score has modest predictive capacity for MACCE in CTO PCI.

A megastudy of text-based nudges encouraging patients to get vaccinated at an upcoming doctor's appointment.

Many Americans fail to get life-saving vaccines each year, and the availability of a vaccine for COVID-19 makes the challenge of encouraging vaccination more urgent than ever. We present a large field experiment (N = 47,306) testing 19 nudges delivered to patients via text message and designed to boost adoption of the influenza vaccine. Our findings suggest that text messages sent prior to a primary care visit can boost vaccination rates by an average of 5%. Overall, interventions performed better when they were 1) framed as reminders to get flu shots that were already reserved for the patient and 2) congruent with the sort of communications patients expected to receive from their healthcare provider (i.e., not surprising, casual, or interactive). The best-performing intervention in our study reminded patients twice to get their flu shot at their upcoming doctor's appointment and indicated it was reserved for them. This successful script could be used as a template for campaigns to encourage the adoption of life-saving vaccines, including against COVID-19.

Long-term efficacy and safety of renal denervation in the presence of antihypertensive drugs (SPYRAL HTN-ON MED): a randomised, sham-controlled trial.

BACKGROUND: Renal denervation has been shown to lower blood pressure in the presence of antihypertensive medications; however, long-term safety and efficacy data from randomised trials of renal denervation are lacking. In this pre-specified analysis of the SPYRAL HTN-ON MED study, we compared changes in blood pressure, antihypertensive drug use, and safety up to 36 months in renal denervation versus a sham control group. METHODS: This randomised, single-blind, sham-controlled trial enrolled patients from 25 clinical centres in the USA, Germany, Japan, the UK, Australia, Austria, and Greece, with uncontrolled hypertension and office systolic blood pressure between 150 mm Hg and 180 mm Hg and diastolic blood pressure of 90 mm Hg or higher. Eligible patients had to have 24-h ambulatory systolic blood pressure between 140 mm Hg and less than 170 mm Hg, while taking one to three antihypertensive drugs with stable doses for at least 6 weeks. Patients underwent renal angiography and were randomly assigned (1:1) to radiofrequency renal denervation or a sham control procedure. Patients and physicians were unmasked after 12-month follow-up and sham control patients could cross over after 12-month follow-up completion. The primary endpoint was the treatment difference in mean 24-h systolic blood pressure at 6 months between the renal denervation group and the sham control group. Statistical analyses were done on the intention-to-treat population. Long-term efficacy was assessed using ambulatory and office blood pressure measurements up to 36 months. Drug surveillance was used to assess medication use. Safety events were assessed up to 36 months. This trial is registered with ClinicalTrials.gov, NCT02439775; prospectively, an additional 260 patients are currently being randomly assigned as part of the SPYRAL HTN-ON MED Expansion trial. FINDINGS: Between July 22, 2015, and June 14, 2017, among 467 enrolled patients, 80 patients fulfilled the qualifying criteria and were randomly assigned to undergo renal denervation (n=38) or a sham control procedure (n=42). Mean ambulatory systolic and diastolic blood pressure were significantly reduced from baseline in the renal denervation group, and were significantly lower than the sham control group at 24 and 36 months, despite a similar treatment intensity of antihypertensive drugs. The medication burden at 36 months was 2·13 medications (SD 1·15) in the renal denervation group and 2·55 medications (2·19) in the sham control group (p=0·26). 24 (77%) of 31 patients in the renal denervation group and 25 (93%) of 27 patients in the sham control group adhered to medication at 36 months. At 36 months, the ambulatory systolic blood pressure reduction was -18·7 mm Hg (SD 12·4) for the renal denervation group (n=30) and -8·6 mm Hg (14·6) for the sham control group (n=32; adjusted treatment difference -10·0 mm Hg, 95% CI -16·6 to -3·3; p=0·0039). Treatment differences between the renal denervation group and sham control group at 36 months were -5·9 mm Hg (95% CI -10·1 to -1·8; p=0·0055) for mean ambulatory diastolic blood pressure, -11·0 mm Hg (-19·8 to -2·1; p=0·016) for morning systolic blood pressure, and -11·8 mm Hg (-19·0 to -4·7; p=0·0017) for night-time systolic blood pressure. There were no short-term or long-term safety issues associated with renal denervation. INTERPRETATION: Radiofrequency renal denervation compared with sham control produced a clinically meaningful and lasting blood pressure reduction up to 36 months of follow-up, independent of concomitant antihypertensive medications and without major safety events. Renal denervation could provide an adjunctive treatment modality in the management of patients with hypertension. FUNDING: Medtronic.

Capillary-Scale Hydrogel Microchannel Networks by Wire Templating.

Microvascular networks are essential for the efficient transport of nutrients, waste products, and drugs throughout the body. Wire-templating is an accessible method for generating laboratory models of these blood vessel networks, but it has difficulty fabricating microchannels with diameters of ten microns and narrower, a requirement for modeling human capillaries. This study describes a suite of surface modification techniques to  selectively control the interactions amongst wires, hydrogels, and world-to-chip interfaces. This wire templating method enables the fabrication of perfusable hydrogel-based rounded cross-section capillary-scale networks whose diameters controllably narrow at bifurcations down to 6.1 ± 0.3 microns in diameter. Due to its low cost, accessibility, and compatibility with a wide range of common hydrogels of tunable stiffnesses such as collagen, this technique may increase the fidelity of experimental models of capillary networks for the study of human health and disease.

Impact of lesion length on the outcomes of chronic total occlusion percutaneous coronary intervention: Insights from the PROGRESS-CTO registry.

BACKGROUND: The impact of occlusion length on the procedural techniques and outcomes of chronic total occlusion (CTO) percutaneous coronary intervention (PCI) has received limited study. METHODS: We examined the clinical and angiographic characteristics and procedural outcomes of 10,335 CTO PCIs at 42 US and non-US centers between 2012 and 2022. The cohort was divided into two groups based on lesion length (≥20 mm vs. <20 mm). RESULTS: Long lesions were present in 7208 (70%) patients. Comorbidities were more common in patients with long CTOs. Compared with short lesions, long lesions had higher J-CTO score (2.8 ± 1.1 vs. 1.3 ± 1; p < 0.001) and retrograde wiring was more often the initial (15.5% vs. 4.0%; p < 0.001) and successful (22.8% vs. 8.2%; p < 0.001) crossing strategy. Long lesions were more likely to require longer procedure (123 vs. 91 min; p < 0.001) and fluoroscopy (47.1 vs. 32.2 min; p < 0.001) time, larger contrast volume (218 vs. 200 mL; p < 0.001) and higher air kerma radiation dose (2.4 vs. 1.7 Gy; p < 0.001). After adjusting for potential confounders, long lesions were associated with lower technical success (odds ratio [OR]: 0.91 per 10 mm increase; 95% confidence interval [CI]: 0.88, 0.94) and higher major adverse cardiovascular events (MACE) (OR: 1.08 per 10 mm increase; 95% CI: 1.02, 1.15). CONCLUSIONS: CTO PCI of long occlusions is independently associated with lower rates of technical success and higher rates of in-hospital MACE.

Balloon-assisted subintimal entry (BASE) in chronic total occlusion percutaneous coronary interventions.

BACKGROUND: There is limited data on the use of the balloon-assisted subintimal entry (BASE) technique in chronic total occlusion (CTO) percutaneous coronary intervention (PCI). METHODS: We analyzed the baseline clinical and angiographic characteristics and outcomes of 155 CTO PCIs that utilized the BASE technique at 31 US and non-US centers between 2016 and 2023. RESULTS: The BASE technique was used in 155 (7.9%) of 1968 antegrade dissection and re-entry (ADR) cases performed during the study period. The mean age was 66 ± 10 years, 88.9% of the patients were men, and the prevalence of diabetes (44.6%), hypertension (90.5%), and dyslipidemia (88.7%) was high. Compared with 1813 ADR cases that did not use BASE, the target vessel of the BASE cases was more commonly the RCA and less commonly the LAD. Lesions requiring BASE had longer occlusion length (42 ± 23 vs. 37 ± 23 mm, p = 0.011), higher Japanese CTO (J-CTO) (3.4 ± 1.0 vs. 3.0 ± 1.1, p < 0.001) and PROGRESS-CTO (Prospective Global Registry for the Study of Chronic Total Occlusion Intervention chronic total occlusion) (1.8 ± 1.0 vs. 1.5 ± 1.0, p = 0.008) scores, and were more likely to have proximal cap ambiguity, side branch at the proximal cap, blunt/no stump, moderate to severe calcification, and proximal tortuosity. Technical (71.6% vs. 75.5%, p = 0.334) and procedural success (71.6% vs. 72.8%, p = 0.821), as well as major adverse cardiac events (MACE) (1.3% vs. 4.1%, p = 0.124), were similar in ADR cases that used BASE and those that did not. CONCLUSIONS: The BASE technique is used in CTOs with longer occlusion length, higher J-CTO score, and more complex angiographic characteristics, and is associated with moderate success but also low MACE.

Impact of preprocedural anemia on in-hospital and follow-up outcomes of chronic total occlusion percutaneous coronary intervention.

BACKGROUND: The impact of preprocedural anemia on the outcomes of chronic total occlusion (CTO) percutaneous coronary intervention (PCI) has received limited study. METHODS: We examined the clinical and angiographic characteristics and procedural outcomes of 8633 CTO PCIs performed at 39 US and non-US centers between 2012 and 2023. Anemia was defined as a hemoglobin level of <13 g/dL in men and <12 g/dL in women. RESULTS: Anemia was present in 1652 (19%) patients undergoing CTO PCI. Anemic patients had a higher incidence of comorbidities, such as diabetes mellitus, hypertension, dyslipidemia, heart failure, cerebrovascular disease, and peripheral arterial disease. CTOs in anemic patients were more likely to have complex angiographic characteristics, including smaller diameter, longer length, moderate to severe calcification, and moderate to severe proximal tortuosity. Anemic patients required longer procedure (119 vs. 107 min; p < 0.001) and fluoroscopy (45 vs. 40 min; p < 0.001) times but received similar contrast volumes. Technical success was similar between the two groups. In-hospital major adverse cardiac events (MACE) rates were higher in patients with anemia; however, this association was no longer significant after adjusting for confounding factors. Baseline anemia was independently associated with follow-up MACE (adjusted hazard ratio [HR]: 1.63; 95% confidence interval [CI]: 1.07-2.49; p = 0.023) and all-cause mortality (adjusted HR: 3.03; 95% CI: 1.41-6.49; p = 0.004). CONCLUSIONS: Preprocedural anemia is associated with more comorbidities, higher lesion complexity, longer procedure times, and higher follow-up MACE and mortality after CTO PCI.

Aortocoronary dissection during percutaneous coronary interventions for chronic total occlusion: Insights from the PROGRESS-CTO registry.

BACKGROUND: Aortocoronary dissection is a potentially serious complication of chronic total occlusion (CTO) percutaneous coronary intervention (PCI). METHODS: We examined the incidence, mechanisms, treatment, and outcomes of aortocoronary dissection among 12,117 CTO PCIs performed between 2012 and 2022 in a large multicenter CTO PCI registry. RESULTS: The incidence of aortocoronary dissection was 0.2% (n = 27). Most aortocoronary dissections occurred in the right coronary artery (96.3%, n = 26). The baseline clinical characteristics of patients with and without aortocoronary dissection were similar, except for dyslipidemia, which was less common in patients with aortocoronary dissection (70.4% vs. 86.0%; p = 0.019). The retrograde approach was used more commonly among cases complicated by aortocoronary dissection (59.3% vs. 31.0%; p = 0.002). Technical (74.1% vs. 86.6%; p = 0.049) and procedural (70.4% vs. 85.2%; p = 0.031) success rates were lower among aortocoronary dissection cases, with a similar incidence of in-hospital major adverse cardiovascular events (3.7% vs. 2.0%; p = 0.541). Of the 27 patients with aortocoronary dissection, 19 (70.4%) were treated with ostial stenting and 8 (29.6%) were treated conservatively without subsequent adverse clinical outcomes. No patients required emergency surgery. Follow-up was available for 22 patients (81.5%): during a mean follow up of 767 (±562) days, the incidence of in-stent restenosis was 11.1% (n = 3). CONCLUSIONS: Aortocoronary dissection occurred in 0.2% of CTO PCIs performed by experienced operators, was associated with lower technical and procedural success, and was treated most commonly with ostial stenting. None of the patients required emergency cardiac surgery.

Same day discharge versus overnight observation following chronic total occlusion percutaneous coronary intervention: Insights from the PROGRESS-CTO registry.

BACKGROUND: Same day discharge (SDD) following chronic total occlusion (CTO) percutaneous coronary intervention (PCI) has received limited study. METHODS: We evaluated the clinical, angiographic, and procedural characteristics of patients discharged the same day versus those kept for overnight observation in the Prospective Global Registry for the Study of Chronic Total Occlusion Intervention (PROGRESS-CTO, NCT02061436). RESULTS: Of the 7181 patients who underwent CTO PCI, 943 (13%) had SDD. The SDD rate increased from 3% in 2015 to 21% in 2022. Patients with SDD were less likely to have a history of heart failure (21% vs. 26%, p = 0.005), chronic lung disease (10% vs. 15%, p = 0.001), or anemia (12% vs. 19%, p < 0.001). Technical success (87% vs. 88%, p = 0.289) was similar, but in-hospital major adverse cardiovascular events (0.0% vs. 0.4%, p = 0.041) were lower in SDD. In multivariable logistic regression analysis, prior myocardial infarction odds ratio (OR): 0.71 (95% confidence interval [CI]: 0.59-0.87, p = 0.001), chronic lung disease OR: 0.64 (95% CI: 0.47-0.88, p = 0.006), and increasing procedure time OR: 0.93 (95% CI: 0.91-0.95, p < 0.001, per 10-min increase) were associated with overnight observation, while radial-only access OR: 2.45 (95% CI: 2.03-2.96, p < 0.001) had the strongest association with SDD. In the SDD, 2 (0.4%) of 514 patients were readmitted, due to retroperitoneal bleeding (n = 1) and ischemic stroke (n = 1). CONCLUSION: The overall frequency of SDD after CTO PCI was 13% and has been increasing over time. SDD is feasible in select patients following CTO PCI, and radial-only access had the strongest association with SDD.

Single vs. multiple operators for chronic total occlusion percutaneous coronary interventions: From the PROGRESS-CTO Registry.

BACKGROUND: There is limited data on the impact of a second attending operator on chronic total occlusion (CTO) percutaneous coronary intervention (PCI) outcomes. METHODS: We analyzed the association between multiple operators (MOs) (>1 attending operator) and procedural outcomes of 9296 CTO PCIs performed between 2012 and 2021 at 37 centers. RESULTS: CTO PCI was performed by a single operator (SO) in 85% of the cases and by MOs in 15%. Mean patient age was 64.4 ± 10 years and 81% were men. SO cases were more complex with higher Japan-CTO (2.38 ± 1.29 vs. 2.28 ± 1.20, p = 0.005) and Prospective Global Registry for the Study of Chronic Total Occlusion Intervention scores (1.13 ± 1.01 vs. 0.97 ± 0.93, p < 0.001) compared with MO cases. Procedural time (131 [87, 181] vs. 112 [72, 167] min, p < 0.001), fluoroscopy time (49 [31, 76] vs. 42 [25, 68] min, p < 0.001), air kerma radiation dose (2.32 vs. 2.10, p < 0.001), and contrast volume (230 vs. 210, p < 0.001) were higher in MO cases. Cases performed by MOs and SO had similar technical (86% vs. 86%, p = 0.9) and procedural success rates (84% vs. 85%, p = 0.7), as well as major adverse complication event rates (MACE 2.17% vs. 2.42%, p = 0.6). On multivariable analyses, MOs were not associated with higher technical success or lower MACE rates. CONCLUSION: In a contemporary, multicenter registry, 15% of CTO PCI cases were performed by multiple operators. Despite being more complex, SO cases had lower procedural and fluoroscopy times, and similar technical and procedural success and risk of complications compared with MO cases.

Incidence, mechanisms, treatment, and outcomes of donor vessel injury during percutaneous coronary interventions for chronic total occlusion.

BACKGROUND: Donor vessel injury is a potentially life-threatening complication of chronic total occlusion (CTO) percutaneous coronary intervention (PCI). AIMS: Our goal was to examine the incidence, mechanisms, treatment, and outcomes of patients with donor vessel injury in a large multicenter CTO PCI registry. METHODS: We analyzed the baseline clinical and angiographic characteristics, and procedural outcomes of 12,349 CTO PCIs performed between 2012 and 2022 at 44 centers. RESULTS: The incidence of donor vessel injury was 0.35% (n = 43). The baseline clinical characteristics of patients with and without donor vessel injury were similar. Cases complicated by donor vessel injury were more complex with higher Japanese CTO score (2.9 ± 1.1 vs. 2.4 ± 1.3; p = 0.004) and lower procedural success rate (69.8% vs. 85.2%; p = 0.004). The retrograde approach was used more commonly in donor vessel injury cases (68.9% vs. 30.9%; p < 0.001). Most (53.5%) donor vessel injuries were guide catheter-induced, whereas 20.9% were due to donor vessel thrombosis. Of the 43 patients with donor vessel injury, 36 (83.7%) were treated with stenting and seven (16.3%) received a left ventricular assist device. The incidence of major adverse cardiovascular events (MACEs) was significantly higher in cases with donor vessel injury (23.3% vs. 2.0%; p < 0.001). Of the 43 patients with donor vessel injury, five patients (11.6%) experienced acute myocardial infarction and four patients (9.3%) died. CONCLUSIONS: Donor vessel injury, occurred in 0.35% of CTO PCIs performed by experienced operators, was mainly due to guide catheter-induced dissection or thrombosis and was associated with lower procedural success and higher MACE.

External validation of the PROGRESS-CTO perforation risk score: Individual patient data pooled analysis of three registries.

BACKGROUND: Coronary artery perforation is one of the most feared and common complications of chronic total occlusion (CTO) percutaneous coronary intervention (PCI). METHODS: To assess the usefulness of the recently developed PROGRESS-CTO (NCT02061436) perforation risk score in independent cohorts. Individual patient-level data pooled analysis of three registries was performed. RESULTS: Of the 4566 patients who underwent CTO PCI at 25 centers, 196 (4.2%) had coronary artery perforation. Patients with perforations were older (69 ± 10 vs. 65 ± 10, p < 0.001), more likely to be women (19% vs. 13%, p = 0.009), more likely to have a history of prior coronary artery bypass graft (34% vs. 20%, p < 0.001), and unfavorable angiographic characteristics such as blunt stump (62% vs. 48%, p < 0.001), proximal cap ambiguity (52% vs. 34%, p < 0.001), and moderate-severe calcification (60% vs. 49%, p = 0.002). Technical success was lower in patients with perforations (73% vs. 88%, p < 0.001). The area under the receiver operating characteristic curve of the PROGRESS-CTO perforation risk model was 0.76 (95% confidence interval [CI], 0.72-0.79), with good calibration (Hosmer-Lemeshow p = 0.97). We found that the CTO PCI perforation risk increased with higher PROGRESS-CTO perforation scores: 0.3% (score 0), 2.3% (score 1), 3.1% (score 2), 5.5% (score 3), 7.5% (score 4), 14.6% (score 5). CONCLUSION: Given the good discriminative performance, calibration, and the ease of calculation, the PROGRESS-CTO perforation score may facilitate assessment of the risk of perforation in patients undergoing CTO PCI.

Myelin and non-myelin debris contribute to foamy macrophage formation after spinal cord injury.

Tissue damage after spinal cord injury (SCI) elicits a robust inflammatory cascade that fails to resolve in a timely manner, resulting in impaired wound healing and cellular regeneration. This inflammatory response is partly mediated by infiltrating immune cells, including macrophages. As professional phagocytes, macrophages initially play an important role in debris clearance at the injury site, which would be necessary for proper tissue regeneration. After SCI, most macrophages become filled with lipid droplets due to excessive uptake of lipid debris, assuming a "foamy" phenotype that is associated with a proinflammatory state. Myelin has been assumed to be the main source of lipid that induces foamy macrophage formation after injury given its abundance in the spinal cord. This assumption has led to the widespread use of purified myelin treatment to model foamy macrophage formation in vitro. However, the assumption that myelin is necessary for foamy macrophage formation remains untested. To this end, we developed a novel foamy macrophage assay utilizing total spinal cord homogenate to include all sources of lipid present at the injury site. Using the myelin basic protein knockout (MBP KO, i.e., Shiverer) mice that lack myelin, we investigated lipid accumulation in foamy macrophages. Primary macrophages treated with myelin-deficient spinal cord homogenate still formed large lipid droplets typically observed in foamy macrophages, although to a lesser degree than cells treated with normal homogenate. Similarly, MBP KO mice subjected to contusive spinal cord injury also formed foamy macrophages that exhibited reduced lipid content and associated with improved histological outcomes and reduced immune cell infiltration. Therefore, the absence of myelin does not preclude foamy macrophage formation, indicating that myelin is not the only major source of lipid that contributes this pathology, even though myelin may alter certain aspects of its inflammatory profile.

Clinical outcomes according to lesion complexity in high bleeding risk patients treated with 1-month dual antiplatelet therapy following PCI: Analysis from the Onyx ONE clear study.

OBJECTIVES: To compare clinical outcomes in high bleeding risk (HBR) patients with and without complex percutaneous coronary intervention (PCI) treated with Resolute Onyx zotarolimus-eluting stents (ZES) after 1-month dual antiplatelet therapy (DAPT). BACKGROUND: PCI with 1-month DAPT has been demonstrated to be safe in HBR patients treated with Resolute Onyx ZES. Whether these outcomes are consistent in patients with complex lesions is uncertain. METHODS: Among HBR patients who were event-free 1 month after PCI with ZES and treated thereafter with single antiplatelet therapy (SAPT), the clinical outcomes between 1 month and 1 year were compared after complex PCI (3 vessels treated, ≥ 3 lesions treated, total stent length > 60 mm, bifurcation with ≥ 2 stents implanted, atherectomy, or left main, surgical bypass graft or chronic total occlusion PCI) versus noncomplex PCI. Propensity score adjustment was performed to adjust for baseline differences among complex and noncomplex patients. RESULTS: Complex patients (N = 401, 26.6% of total) had a higher prevalence of hyperlipidemia, diabetes mellitus and previous myocardial infarction (MI). Between 1 month and 1 year, rates of MI (7.1% vs. 4.0%, p = 0.02) and cardiac death/MI (9.3% vs. 6.1%, p = 0.04) were higher among complex versus noncomplex patients, although stent thrombosis rates were similar. After adjustment for baseline characteristics, differences in outcomes were no longer significant between groups. CONCLUSIONS: Higher rates of ischemic outcomes in complex PCI patients were largely explained by baseline clinical differences, rather than lesion complexity, among HBR patients treated with 1-month DAPT following PCI with Resolute Onyx ZES.

Characteristics and Patterns of Facial Fractures in the Elderly Population in the United States Based on Trauma Quality Improvement Project Data.

ABSTRACT: With the increase in the elderly population in the United States, the number of people seeking care for trauma injuries is expected to increase. However, nationwide studies on epidemiological profile of elderly facial fractures remain sparse. The authors present the epidemiological measures of elderly facial fractures on national scale. Characteristics of facial fractures among younger adults (18-64 years old) and the elderly population (65-74 years old, 75-84 years old and 85 years and above) have been examined using the 2016 American College of Surgeons-Trauma Quality Improvement Program databank. Variables studied included facial fracture patterns, mechanisms of injury, treatment variables, and demographic descriptive data. Of 104,183 elderly trauma patients, 3415 presented with facial fractures, making up 3.3% (versus 6.5% in younger adults). Majority of facial fractures in 85 and over group (60.7%) were experienced by females, compared to only 19.5% in the younger adult group. Most common mechanism of injury in the elderly was falls, versus motor vehicle trauma in younger adults. The most common type of facial fractures among both groups were nasal fractures. Elderly patients presented with fewer zygoma, mandibular and nasal fractures when compared to younger adults, whereas showing more maxillary/malar and orbital bone fractures. Elderly patients experienced less operative management (4.3%-8.2%) compared to younger adults (15.6%). Concurrently, mortality rates were higher in the elderly patients (9.9%-11.8%) when compared to the younger adults (8.0%). Elderly patients presented with different causes of injury, distribution of fractures, and rates of operative management compared to younger adults.

Optimized digital shade calibration technology for the restoration of a single central incisor.

Predictable shade matching and communicating shade information to the dental laboratory technician have proved to be a capricious undertaking. Numerous confounding variables exist for the observer-which may be extrinsic (such as light source and background color), intrinsic (such as genetics and eye fatigue), or a combination of both. To address these shortcomings, low-cost, easy-to-operate, color analysis instrumentation and software programs have been engineered for objective shade selection and precise color analysis. The shade matching protocols that now exist have made even the most challenging esthetic treatments predictable for both the clinician and the dental laboratory technician.

Efficacy of catheter-based renal denervation in the absence of antihypertensive medications (SPYRAL HTN-OFF MED Pivotal): a multicentre, randomised, sham-controlled trial.

BACKGROUND: Catheter-based renal denervation has significantly reduced blood pressure in previous studies. Following a positive pilot trial, the SPYRAL HTN-OFF MED (SPYRAL Pivotal) trial was designed to assess the efficacy of renal denervation in the absence of antihypertensive medications. METHODS: In this international, prospective, single-blinded, sham-controlled trial, done at 44 study sites in Australia, Austria, Canada, Germany, Greece, Ireland, Japan, the UK, and the USA, hypertensive patients with office systolic blood pressure of 150 mm Hg to less than 180 mm Hg were randomly assigned 1:1 to either a renal denervation or sham procedure. The primary efficacy endpoint was baseline-adjusted change in 24-h systolic blood pressure and the secondary efficacy endpoint was baseline-adjusted change in office systolic blood pressure from baseline to 3 months after the procedure. We used a Bayesian design with an informative prior, so the primary analysis combines evidence from the pilot and Pivotal trials. The primary efficacy and safety analyses were done in the intention-to-treat population. This trial is registered at ClinicalTrials.gov, NCT02439749. FINDINGS: From June 25, 2015, to Oct 15, 2019, 331 patients were randomly assigned to either renal denervation (n=166) or a sham procedure (n=165). The primary and secondary efficacy endpoints were met, with posterior probability of superiority more than 0·999 for both. The treatment difference between the two groups for 24-h systolic blood pressure was -3·9 mm Hg (Bayesian 95% credible interval -6·2 to -1·6) and for office systolic blood pressure the difference was -6·5 mm Hg (-9·6 to -3·5). No major device-related or procedural-related safety events occurred up to 3 months. INTERPRETATION: SPYRAL Pivotal showed the superiority of catheter-based renal denervation compared with a sham procedure to safely lower blood pressure in the absence of antihypertensive medications. FUNDING: Medtronic.