Geographic diversity in chronic total occlusion percutaneous coronary intervention: insights from the PROGRESS-CTO registry.

BACKGROUND: There is variability in clinical and lesion characteristics as well as techniques in chronic total occlusion (CTO) percutaneous coronary intervention (PCI). METHODS: We analyzed patient and lesion characteristics, techniques, and outcomes in 11 503 CTO-PCI procedures performed in North America (NA) and in the combined regions of Europe, Asia, and Africa from 2017 to 2023 as documented in the PROGRESS-CTO registry. RESULTS: Eight thousand four hundred seventy-nine (74%) procedures were performed in NA. Compared with non-NA patients, NA patients were older, with higher body mass index and higher prevalence of diabetes, hypertension, dyslipidemia, family history of coronary artery disease, prior history of PCI, coronary artery bypass graft surgery and heart failure, cerebrovascular disease, and peripheral arterial disease. Their CTOs were more complex, with higher J-CTO (2.56 ± 1.22 vs 1.81 ± 1.24; P less than .001) and PROGRESS-CTO (1.29 ± 1.01 vs 1.07 ± 0.95; P less than .001) scores, longer length, and higher prevalence of proximal cap ambiguity, blunt/no stump, moderate to severe calcification, and proximal tortuosity. Retrograde (31.0% vs 22.1%; P less than .001) and antegrade dissection and re-entry (ADR) (21.2% vs 9.2%; P less than .001) were more commonly used in NA centers, along with intravascular ultrasound (69.0% vs 10.1%; P less than .001). Procedure and fluoroscopy times were longer in NA, while contrast volume and radiation dose were lower. Technical (86.7% vs 86.8%; P > .90) and procedural (85.4% vs 85.8%; P = .70) success and in-hospital major adverse cardiovascular events (MACE) (1.9% vs 1.7%; P = .40) were similar in NA and non-NA centers. CONCLUSIONS: Compared with non-NA patients, NA patients undergoing CTO PCI have more comorbidities, higher CTO lesion complexity, are more likely to undergo treatment with retrograde and ADR, and have similar technical success and MACE.

Emergency coronary artery bypass surgery after chronic total occlusion percutaneous coronary intervention: Insights from the PROGRESS-CTO registry.

BACKGROUND: Emergency coronary artery bypass surgery (eCABG) is a serious complication of chronic total occlusion (CTO) percutaneous coronary artery intervention (PCI). METHODS: We examined the incidence and outcomes eCABG among 14,512 CTO PCIs performed between 2012 and 2023 in a large multicenter registry. RESULTS: The incidence of eCABG was 0.12% (n = 17). Mean age was 68 ± 6 years and 69% of the patients were men. The most common reason for eCABG was coronary perforation (70.6%). eCABG patients had larger target vessel diameter (3.36 ± 0.50 vs. 2.90 ± 0.52; p = 0.003), were more likely to have moderate/severe calcification (85.7% vs. 45.8%; p = 0.006), side branch at the proximal cap (91.7% vs. 55.4%; p = 0.025), and balloon undilatable lesions (50% vs. 7.4%; p = 0.001) and to have undergone retrograde crossing (64.7% vs. 30.8%, p = 0.006). eCABG cases had lower technical (35.3% vs. 86.7%; p < 0.001) and procedural (35.3% vs. 86.7%; p < 0.001) success and higher in-hospital mortality (35.3% vs. 0.4%; p < 0.001), coronary perforation (70.6% vs. 4.6%; p < 0.001), pericardiocentesis (47.1% vs. 0.8%; p < 0.001), and major bleeding (11.8% vs. 0.5%; p < 0.001). CONCLUSIONS: The incidence of eCABG after CTO PCI was 0.12% and associated with high in-hospital mortality (35%). Coronary perforation was the most common reason for eCABG.

Racial disparities in chronic total occlusion percutaneous coronary interventions: insights from the PROGRESS-CTO registry.

OBJECTIVES: There is limited data on race and outcomes of chronic total occlusion (CTO) percutaneous coronary intervention (PCI). The authors sought to evaluate CTO PCI techniques and outcomes in different racial groups. METHODS: We examined the baseline characteristics and procedural outcomes of 11 806 CTO PCIs performed at 44 US and non-US centers between 2012 and March 2023. In-hospital major adverse cardiac events (MACE) included death, myocardial infarction, repeat target-vessel revascularization, pericardiocentesis, cardiac surgery, and stroke prior to discharge. RESULTS: The most common racial group was White (84.5%), followed by Black (5.7%), "Other" (3.9%), Hispanic (2.9%), Asian (2.4%), and Native American (0.7%). There were significant differences in the baseline characteristics between different racial groups. When compared with non-White patients, the retrograde approach and antegrade dissection re-entry were more likely to be the successful crossing strategies in White patients without any significant differences in technical success (86.4% vs 86.4%; P = .93), procedural success (84.8% vs 85.0%; P = .79), and in-hospital MACE (2.0% vs 1.5%; P = .15) between the 2 groups. The technical success rate was significantly higher in the "Other" racial group (91.0% vs 86.4% in White, 86.9% in Asian, 84.5% in Black, 84.5% in Hispanic, and 83.3% in Native American; P = .03) without any significant differences in procedural success or in-hospital MACE rates between the groups. CONCLUSIONS: Despite differences in baseline characteristics and procedural techniques, the procedural success and in-hospital MACE of CTO PCI were not significantly different between most racial groups.

Equipment entrapment/loss during chronic total occlusion percutaneous coronary intervention.

BACKGROUND: There is limited data on equipment loss or entrapment during chronic total occlusion (CTO) percutaneous coronary intervention (PCI). METHODS: We analyzed the baseline clinical and angiographic characteristics and outcomes of equipment loss/entrapment at 43 US and non-US centers between 2017 and 2023. RESULTS: Equipment loss/entrapment was reported in 40 (0.4%) of 10 719 cases during the study period. These included guidewire entrapment/fracture (n = 21), microcatheter entrapment/fracture (n = 11), stent loss (n = 8) and balloon entrapment/fracture/rupture (n = 5). The equipment loss/entrapment cases were more likely to have moderate to severe calcification, longer lesion length, higher J-CTO and PROGRESS-CTO complications scores, and use of the retrograde approach compared with the remaining cases. Retrieval was attempted in 71.4% of the guidewire, 90.9% of the microcatheter, 100% of the stent loss, and 100% of the balloon cases, and was successful in 26.7%, 30.0%, 50%, and 40% of the cases, respectively. Procedures complicated by equipment loss/entrapment had higher procedure and fluoroscopy time, contrast volume and patient air kerma radiation dose, lower procedural (60.0% vs 85.6%, P less than .001) and technical (75.0% vs 86.8%, P = .05) success, and higher incidence of major adverse cardiac events (MACE) (17.5% vs 1.8%, P less than .001), acute MI (7.5% vs 0.4%, P less than .001), emergency coronary artery bypass graft (CABG) (2.5% vs 0.1%, P = .03), perforation (20.0% vs 4.9%, P less than .001), and death (7.5% vs 0.4%, P less than .001). CONCLUSIONS: Equipment loss is a rare complication of CTO PCI; it is more common in complex CTOs and is associated with lower technical success and higher MACE.

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.

The Retrograde Approach to Chronic Total Occlusion Percutaneous Coronary Interventions: Technical Analysis and Procedural Outcomes.

BACKGROUND: Retrograde chronic total occlusion (CTO) percutaneous coronary intervention (PCI) is associated with lower success and higher complication rates when compared with the antegrade approach. OBJECTIVES: This study sought to assess contemporary techniques and outcomes of retrograde CTO PCI. METHODS: We examined the baseline characteristics, procedural techniques and outcomes of 4,058 retrograde CTO PCIs performed at 44 centers between 2012 and 2023. Major adverse cardiac events (MACE) included any of the following in-hospital events: death, myocardial infarction, repeat target vessel revascularization, pericardiocentesis, cardiac surgery, and stroke. RESULTS: The average J-CTO (Multicenter CTO Registry in Japan) score was 3.1 ± 1.1. Retrograde crossing was successful in 60.5% and lesion crossing in 81.6% of cases. The collaterals pathways successfully used were septals in 62.0%, saphenous vein grafts in 17.4%, and epicardials in 19.1%. The technical and procedural success rates were 78.7% and 76.6%, respectively. When retrograde crossing failed, technical success was achieved in 50.3% of cases using the antegrade approach. In-hospital MACE was 3.5%. The clinical coronary perforation rate was 5.8%. The incidence of in-hospital MACE with retrograde true lumen crossing, just marker antegrade crossing, conventional reverse controlled antegrade and retrograde tracking (CART), contemporary reverse CART, extended reverse CART, guide-extension reverse CART, and CART was 2.1%, 0.8%, 5.5%, 3.0%, 2.1%, 3.2%, and 4.1%, respectively; P = 0.01). CONCLUSIONS: Retrograde CTO PCI is utilized in highly complex cases and yields moderate success rates with 5.8% perforation and 3.5% periprocedural MACE rates. Among retrograde crossing strategies, retrograde true lumen puncture was the safest. There is need for improvement of the efficacy and safety of retrograde CTO PCI.

Use of the Carlino Technique in Chronic Total Occlusion Percutaneous Coronary Intervention.

We examined the outcomes of the Carlino technique in chronic total occlusion (CTO) percutaneous coronary interventions (PCIs). We analyzed the baseline clinical and angiographic characteristics and outcomes of 128 CTO PCIs that included the Carlino technique at 22 US and no-US centers between 2016 and 2023. The Carlino technique was used in 128 (2.8%) of 4,508 cases that used anterograde dissection and reentry (78.9%) or the retrograde approach (21.1%) during the study period, and it increased steadily over time (from 0.0% in 2016 to 8.3% in 2023). The mean patient age was 65.6 ± 9.7 years, and 88.7% of the patients were men with high prevalence of hypertension (89.1%) and dyslipidemia (80.2%). The Carlino technique was more commonly used in cases with moderate to severe calcification (77.2% vs 55.5%, p <0.001) with higher J-CTO (3.3 ± 0.9 vs 3.0 ± 1.1, p = 0.007), Prospective Global Registry for the Study of Chronic Total Occlusion Intervention (PROGRESS-CTO) (1.7 ± 1.0 vs 1.4 ± 1.0, p = 0.001), PROGRESS-CTO Mortality (2.6 ± 0.9 vs 2.0 ± 0.9, p = 0.013) and PROGRESS-CTO Perforation (3.7 ± 1.1 vs 3.5 ± 1.0, p = 0.029) scores. Carlino cases had longer procedure and fluoroscopy time, and higher contrast volume and radiation dose. Carlino cases had lower technical (65.6% vs 78.5%, p <0.001) and procedural (63.3% vs 76.3%, p <0.001) success, similar major adverse cardiac events (6.2% vs 3.2%, p = 0.101) and higher incidence of pericardiocentesis (3.9% vs 1.3%, p = 0.042), perforation (18.0% vs 8.9%, p = 0.001) and contrast-induced acute kidney injury (2.3% vs 0.4%, p = 0.012). The Carlino technique was associated with higher procedural success when used for retrograde crossing (81.5% vs 58.4%, p = 0.047). The Carlino technique is increasingly being used in CTO PCI especially for higher complexity lesions.

Outcomes of Chronic Total Occlusion Percutaneous Coronary Interventions in Patients With Previous Coronary Artery Bypass Graft Surgery.

The outcomes of chronic total occlusion (CTO) percutaneous coronary interventions (PCIs) in patients with previous coronary artery bypass graft (CABG) surgery have received limited study. We examined the baseline characteristics and outcomes of CTO PCIs performed at 47 United States and non-United States centers between 2012 and 2023. Of the 12,164 patients who underwent CTO PCI during the study period, 3,475 (29%) had previous CABG. Previous CABG patients were older, more likely to be men, and had more comorbidities and lower left ventricular ejection fraction and estimated glomerular filtration rate. Their CTOs were more likely to have moderate/severe calcification and proximal tortuosity, proximal cap ambiguity, longer lesion length, and higher Japanese CTO scores. The first and final successful crossing strategy was more likely to be retrograde. Previous CABG patients had lower technical (82.1% vs 88.2%, p <0.001) and procedural (80.8% vs 86.8%, p <0.001) success, higher in-hospital mortality (0.8% vs 0.3%, p <0.001), acute myocardial infarction (0.9% vs 0.5%, p = 0.007) and perforation (7.0% vs 4.2%, p <0.001) but lower incidence of pericardial tamponade and pericardiocentesis (0.1% vs 1.3%, p <0.001). At 2-year follow-up, the incidence of major adverse cardiac events, repeat PCI and acute coronary syndrome was significantly higher in previous CABG patients, whereas all-cause mortality was similar. In conclusion, patients with previous CABG who underwent CTO PCI had more complex clinical and angiographic characteristics and lower success rate, higher perioperative mortality, and myocardial infarction but lower tamponade, and higher incidence of major adverse cardiac events with similar all-cause mortality during follow-up.

Procedural Time and Outcomes of Chronic Total Occlusion Percutaneous Coronary Intervention.

Chronic total occlusion (CTO) percutaneous coronary interventions (PCIs) can be lengthy procedures. We sought to investigate the effect of procedural time on CTO PCI outcomes. We examined the procedural time required for the various steps of CTO PCI in 6,442 CTO PCIs at 40 US and non-US centers between 2012 and 2022. The mean and median procedure times were 129 ± 76 and 112 minutes, respectively, with no significant change over time. The median times from access to wire insertion, guidewire manipulation time, and post crossing were 20, 32, and 53 minutes, respectively. Lesions crossed in <30 minutes were less complex, as reflected by lower Japanese CTO score (1.89 ± 1.19, p <0.001) than lesions that were not successfully crossed (2.88 ± 1.22) and lesions that were crossed in ≥30 minutes (2.85 ± 1.13). The likelihood of successful crossing if crossing was not achieved after 30, 90, and 180 minutes were a 76.7%, 60.7%, and 42.7%, respectively. The parameters independently associated with ≥30 minutes guidewire manipulation time in patients with a primary antegrade approach included left anterior descending target vessel, proximal cap ambiguity, blunt/no stump, occlusion length, previous failed attempt, medium/severe calcification, and medium/severe tortuosity. The mean duration of CTO PCI is approximately 2 hours (∼20% of time for access to wire insertion, ∼30% wire manipulation time, and ∼50% postwiring time). Guidewire crossing time was shorter in less complex lesions and in cases without complications.

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.

Outcomes of Chronic Total Occlusion Percutaneous Coronary Intervention After a Previous Failed Attempt.

The impact of a previous failure on procedural techniques and outcomes of chronic total occlusion (CTO) percutaneous coronary intervention (PCI) has received limited study. We examined the clinical and angiographic characteristics and procedural outcomes of 9,393 patients who underwent 9,560 CTO PCIs at 42 United States and non-United States centers between 2012 and 2022. A total of 1,904 CTO lesions (20%) had a previous failed PCI attempt. Patients who underwent reattempt CTO PCI were more likely to have a family history of coronary artery disease (37% vs 31%, p <0.001) and dyslipidemia (87.9% vs 84.3%, p <0.001) but were less likely to have heart failure (25.1% vs 29.5%; p <0.001) and cerebrovascular disease (8.7% vs 10.4%, p = 0.04). Patients with previous failure had a higher Japanese CTO (3.33 ± 1.16 vs 2.12 ± 1.19, p <0.001) score and required longer procedure (120 vs 111 minutes, p <0.001) and fluoroscopy (46.9 vs 40.4 minutes, p <0.001) times and higher air kerma radiation dose (2.3 vs 2.1 gray, p = 0.013). Technical success rates (84.3% vs 86.5%, p = 0.011) were lower in patients with a previous failure compared with patients who underwent first-attempt CTO PCI with no significant difference in in-hospital major adverse cardiac events. After adjusting for potential confounders, a previous failure was not associated with technical failure. Operators performing >30 CTO PCIs annually were more likely to achieve technical success in patients with previous failure. In conclusion, a previous failed CTO PCI attempt was associated with higher lesion complexity, longer procedure time, and lower technical success; however, the association with lower technical success did not remain significant in multivariable analysis.

Angiographic Features and Clinical Outcomes of Balloon Uncrossable Lesions during Chronic Total Occlusion Percutaneous Coronary Intervention.

Background: Balloon uncrossable lesions are defined as lesions that cannot be crossed with a balloon after successful guidewire crossing. Methods: We analyzed the association between balloon uncrossable lesions and procedural outcomes of 8671 chronic total occlusions (CTOs) percutaneous coronary interventions (PCIs) performed between 2012 and 2022 at 41 centers. Results: The prevalence of balloon uncrossable lesions was 9.2%. The mean patient age was 64.2 ± 10 years and 80% were men. Patients with balloon uncrossable lesions were older (67.3 ± 9 vs. 63.9 ± 10, p < 0.001) and more likely to have prior coronary artery bypass graft surgery (40% vs. 25%, p < 0.001) and diabetes mellitus (50% vs. 42%, p < 0.001) compared with patients who had balloon crossable lesions. In-stent restenosis (23% vs. 16%. p < 0.001), moderate/severe calcification (68% vs. 40%, p < 0.001), and moderate/severe proximal vessel tortuosity (36% vs. 25%, p < 0.001) were more common in balloon uncrossable lesions. Procedure time (132 (90, 197) vs. 109 (71, 160) min, p < 0.001) was longer and the air kerma radiation dose (2.55 (1.41, 4.23) vs. 1.97 (1.10, 3.40) min, p < 0.001) was higher in balloon uncrossable lesions, while these lesions displayed lower technical (91% vs. 99%, p < 0.001) and procedural (88% vs. 96%, p < 0.001) success rates and higher major adverse cardiac event (MACE) rates (3.14% vs. 1.49%, p < 0.001). Several techniques were required for balloon uncrossable lesions. Conclusion: In a contemporary, multicenter registry, 9.2% of the successfully crossed CTOs were initially balloon uncrossable. Balloon uncrossable lesions exhibited lower technical and procedural success rates and a higher risk of complications compared with balloon crossable lesions.

External validation of the PROGRESS-CTO complication risk scores: Individual patient data pooled analysis of 3 registries.

BACKGROUND: Chronic total occlusion (CTO) percutaneous coronary intervention (PCI) is associated with a considerable risk of complications, and risk stratification is of utmost importance. AIMS: To assess the clinical usefulness of the recently developed PROGRESS-CTO (NCT02061436) complication risk scores in an independent cohort. METHODS: Individual patient data pooled analysis of 3 registries was performed. RESULTS: Of the 4569 patients who underwent CTO PCI, 102 (2.2%) had major adverse cardiovascular events (MACE). Patients with MACE were older (69 ± 11 vs. 65 ± 10, p < 0.001), more likely to have a history of prior coronary artery bypass graft surgery, and unfavorable angiographic characteristics J-CTO score (2.4 ± 1.2 vs. 2.1 ± 1.3, p = 0.007), including blunt stump (59% vs. 49%, p = 0.047). Technical success was lower in patients with MACE (59% vs. 86%, p < 0.001). The area under the receiver operating characteristic curve of the PROGRESS-CTO complication risk models were as follows: MACE 0.72 (95% confidence interval [CI], 0.67-0.76), mortality 0.73 (95% CI, 0.61-0.85), and pericardiocentesis 0.69 (95% CI, 0.62-0.77) in the validation dataset. The observed complication rates increased with higher PROGRESS-CTO complication scores. The PROGRESS-CTO MACE score showed good calibration in this external cohort, with MACE rates similar to the original study: 0.7% (score 0-1), 1.5% (score 2), 2.2% (score 3), 3.8% (score 4), 4.9% (score 5), 5.8% (score 6-7). CONCLUSION: Given the good discriminative performance, calibration, and ease of calculation, the PROGRESS-CTO complication scores could help assess the risk of complications in patients undergoing CTO PCI.

Lung Transplantation for COVID-19 Acute Respiratory Distress Syndrome: The British Columbian Experience With New Disease Pathology.

Lung transplantation is a life-saving treatment for patients with end-stage lung disease. COVID-19 has been associated with a severe and rapid decline in pulmonary function, in which case lung transplantation has been described to be effective. We herein describe 9 patients who underwent lung transplantation for COVID-19 acute respiratory distress syndrome, of whom 6 were bridged with extracorporeal membrane oxygenation (ECMO). The median time of pre-operative observation periods was 54 days to ensure no lung function recovery and the time to wean off extracorporeal membrane oxygenation was 3 days. Patients had comparable short-term survival outcomes to non-COVID-19 lung transplant recipients at our institution during the same time period. Lung transplantation for COVID-19-associated lung disease is feasible with comparable short-term outcomes and may liberate patients from extracorporeal supports.

Uncommon Cause of Internal Mammary Artery Pseudoaneurysm.

Background: Internal mammary artery pseudoaneurysms most commonly develop from thoracic penetrating trauma or procedures. However, other important etiologies should not be overlooked. Case Report: A 27-year-old female presented with antiphospholipid antibody syndrome, thrombotic microangiopathy, end-stage renal disease on hemodialysis, and epilepsy. On admission, the patient had pulseless electrical activity and hypertensive emergency. After the patient was successfully resuscitated, she developed status epilepticus. Laboratory workup on admission revealed a subtherapeutic international normalized ratio, elevated C-reactive protein and sedimentation rate, and acute anemia. Imaging showed a right-sided subdural hematoma with a midline shift and likely internal mammary artery pseudoaneurysm. Angiography demonstrated aneurysmal dilation, segmental narrowing, and a string of beads appearance. Because of our patient's demographics, string of beads appearance on diagnostic angiography, history of renal disease, and negative hepatitis serology, fibromuscular dysplasia was considered the etiology of the internal mammary artery pseudoaneurysm. The family opted for 2 burr holes and a subdural drain but declined further diagnostic and therapeutic interventions because of anoxic brain injury and poor prognosis. Conclusion: In this patient, the etiology of the internal mammary artery pseudoaneurysm was attributed to fibromuscular dysplasia. Although this patient's family chose comfort measures, treatment methods are available for internal mammary artery pseudoaneurysms.

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.

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.

Predicting Periprocedural Complications in Chronic Total Occlusion Percutaneous Coronary Intervention: The PROGRESS-CTO Complication Scores.

BACKGROUND: Chronic total occlusion (CTO) percutaneous coronary intervention (PCI) is associated with increased risk of periprocedural complications. Estimating the risk of complications facilitates risk-benefit assessment and procedural planning. OBJECTIVES: This study sought to develop risk scores for in-hospital major adverse cardiovascular events (MACE), mortality, pericardiocentesis, and acute myocardial infarction (MI) in patients undergoing CTO PCI. METHODS: The study analyzed the PROGRESS-CTO (Prospective Global Registry for the Study of Chronic Total Occlusion Intervention; NCT02061436) and created risk scores for MACE, mortality, pericardiocentesis, and acute MI. Logistic regression prediction modeling was used to identify independently associated variables, and models were internally validated with bootstrapping. RESULTS: The incidence of periprocedural complications among 10,480 CTO PCIs was as follows: MACE 215 (2.05%), mortality 47 (0.45%), pericardiocentesis 83 (1.08%), and acute MI 66 (0.63%). The final model for MACE included ≥65 years of age (1 point), moderate-severe calcification (1 point), blunt stump (1 point), antegrade dissection and re-entry (ADR) (1 point), female (2 points), and retrograde (2 points); the final model for mortality included ≥65 years of age (1 point), left ventricular ejection fraction ≤45% (1 point), moderate-severe calcification (1 point), ADR (1 point), and retrograde (1 point); the final model for pericardiocentesis included ≥65 years of age (1 point), female (1 point), moderate-severe calcification (1 point), ADR (1 point), and retrograde (2 points); the final model for acute MI included prior coronary artery bypass graft surgery (1 point), atrial fibrillation (1 point), and blunt stump (1 point). The C-statistics of the models were 0.74, 0.80, 0.78, 0.72 for MACE, mortality, pericardiocentesis, and acute MI, respectively. CONCLUSIONS: The PROGRESS-CTO complication risk scores can facilitate estimation of the periprocedural complication risk in patients undergoing CTO PCI.

The Clinically Actionable Molecular Profile of Early versus Late-Stage Non-Small Cell Lung Cancer, an Individual Age and Sex Propensity-Matched Pair Analysis.

Background: Despite meticulous surgery for non-small cell lung cancer (NSCLC), relapse is as high as 70% at 5 years. Many institutions do not conduct reflexive molecular testing on early stage specimens, although targeted gene therapy may extend life by years in the event of recurrence. This ultimately delays definitive treatment with additional biopsy risking suboptimal tissue acquisition and quality for molecular testing. Objective: To compare molecular profiles of genetic alterations in early and late NSCLC to provide evidence that reflexive molecular testing provides clinically valuable information. Methods: A single-center propensity matched retrospective analysis was conducted using prospectively collected data. Adults with early and late-stage NSCLC had tissue subject to targeted panel-based NGS. Frequencies of putative drivers were compared, with 1:3 matching on the propensity score; p < 0.05 deemed statistically significant. Results: In total, 635 NSCLC patients underwent NGS (59 early, 576 late); 276 (43.5%) females; age 70.9 (±10.2) years; never smokers 140 (22.0%); 527 (83.0%) adenocarcinomas. Unadjusted frequencies of EGFR mutations were higher in the early cohort (30% vs. 18%). Following adjustment for sex and smoking status, similar frequencies for both early and late NSCLC were observed for variants in EGFR, KRAS, ALK, MET, and ROS1. Conclusion: The frequency of clinically actionable variants in early and late-stage NSCLC was found to be similar, providing evidence that molecular profiling should be performed on surgical specimens. This pre-determined profile is essential to avoid treatment delay for patients who will derive clinical benefit from targeted systemic therapy, in the high likelihood of subsequent relapse.

Serial rotational thromboelastography (ROTEM) in mechanically ventilated patients with COVID-19 demonstrates hypercoagulopathy despite therapeutic heparinization.

Background: Clinical hypercoagulopathy in patients with COVID-19 has been anecdotally described, but there is lack of evidence due to the novelty of this disease. Our study reports the results of rotational thromboelastography (ROTEM) in relation to traditional laboratory coagulation tests and acute phase markers among a cohort of severely ill, mechanically ventilated patients with COVID-19. Methods: Patients with COVID-19 (N=21) with respiratory failure requiring mechanical ventilation were included in this prospective case series. ROTEM was serially obtained for all patients on three different days during their intensive care unit (ICU) stay and analyzed using repeated measures analysis. Demographic variables, symptoms at the time of presentation, ROTEM values, laboratory values for traditionally measured coagulation profiles, and acute phase reactants were analyzed, in addition to the use of anticoagulation and clinical hypercoagulopathic complications. Results: The average age of our cohort was 57.9 years old (SD=14.4) and 76.2% were male. The mortality rate was 14.3% (3 of 21). Two patients (12.5%) were identified to have new-onset deep vein thrombosis, two patients (12.5%) were found to have ≥3 episodes of central venous catheter thrombosis, and three patients (18.7%) had confirmed stroke. ROTEM demonstrated elevated EXTEM and INTEM clotting times, including elevated FIBTEM maximum clot firmness (MCFFIB). All patients treated with therapeutic anticoagulation still demonstrated hypercoagulopathy within the MCFFIB tests. Discussion: Repeated measure ROTEMs were able to detect hypercoagulopathy in ICU patients with COVID-19 despite therapeutic anticoagulation with heparin. Level of evidence: III.