Thoracic aortic microcalcification activity in combined positron emission tomography and magnetic resonance imaging.

INTRODUCTION: Non-invasive detection of pathological changes in thoracic aortic disease remains an unmet clinical need particularly for patients with congenital heart disease. Positron emission tomography combined with magnetic resonance imaging (PET-MRI) could provide a valuable low-radiation method of aortic surveillance in high-risk groups. Quantification of aortic microcalcification activity using sodium [18F]fluoride holds promise in the assessment of thoracic aortopathies. We sought to evaluate aortic sodium [18F]fluoride uptake in PET-MRI using three methods of attenuation correction compared to positron emission tomography computed tomography (PET-CT) in patients with bicuspid aortic valve, METHODS: Thirty asymptomatic patients under surveillance for bicuspid aortic valve disease underwent sodium [18F]fluoride PET-CT and PET-MRI of the ascending thoracic aorta during a single visit. PET-MRI data were reconstructed using three iterations of attenuation correction (Dixon, radial gradient recalled echo with two [RadialVIBE-2] or four [RadialVIBE-4] tissue segmentation). Images were qualitatively and quantitatively analysed for aortic sodium [18F]fluoride uptake on PET-CT and PET-MRI. RESULTS: Aortic sodium [18F]fluoride uptake on PET-MRI was visually comparable with PET-CT using each reconstruction and total aortic standardised uptake values on PET-CT strongly correlated with each PET-MRI attenuation correction method (Dixon R = 0.70; RadialVIBE-2 R = 0.63; RadialVIBE-4 R = 0.64; p < 0.001 for all). Breathing related artefact between soft tissue and lung were detected using Dixon and RadialVIBE-4 but not RadialVIBE-2 reconstructions, with the presence of this artefact adjacent to the atria leading to variations in blood pool activity estimates. Consequently, quantitative agreements between radiotracer activity on PET-CT and PET-MRI were most consistent with RadialVIBE-2. CONCLUSION: Ascending aortic microcalcification analysis in PET-MRI is feasible with comparable findings to PET-CT. RadialVIBE-2 tissue attenuation correction correlates best with the reference standard of PET-CT and is less susceptible to artefact. There remain challenges in segmenting tissue types in PET-MRI reconstructions, and improved attenuation correction methods are required.

CT Attenuation of Periaortic Adipose Tissue in Abdominal Aortic Aneurysms.

Purpose To assess periaortic adipose tissue attenuation at CT angiography in different abdominal aortic aneurysm disease states. Materials and Methods In a retrospective observational study from January 2018 to December 2022, periaortic adipose tissue attenuation was assessed at CT angiography in patients with asymptomatic or symptomatic (including rupture) abdominal aortic aneurysms and controls without aneurysms. Adipose tissue attenuation was measured using semiautomated software in periaortic aneurysmal and nonaneurysmal segments of the abdominal aorta and in subcutaneous and visceral adipose tissue. Periaortic adipose tissue attenuation values between the three groups were assessed using Student t tests and Wilcoxon rank sum tests followed by a multiregression model. Results Eighty-eight individuals (median age, 70 years [IQR, 65-78]; 78 male and 10 female patients) were included: 70 patients with abdominal aortic aneurysms (40 asymptomatic and 30 symptomatic, including 24 with rupture) and 18 controls. There was no evidence of differences in the periaortic adipose tissue attenuation in the aneurysmal segment in asymptomatic patients versus controls (-81.44 HU ± 7 [SD] vs -83.27 HU ± 9; P = .43) and attenuation in nonaneurysmal segments between asymptomatic patients versus controls (-75.43 HU ± 8 vs -78.81 HU ± 6; P = .08). However, symptomatic patients demonstrated higher periaortic adipose tissue attenuation in both aneurysmal (-57.85 HU ± 7; P < .0001) and nonaneurysmal segments (-58.16 HU ± 8; P < .0001) when compared with the other two groups. Conclusion Periaortic adipose tissue CT attenuation was not increased in stable abdominal aortic aneurysm disease. There was a generalized increase in attenuation in patients with symptomatic disease, likely reflecting the systemic consequences of acute rupture. Keywords: Abdominal Aortic Aneurysm, Periaortic Adipose Tissue Attenuation, CT Angiography ClinicalTrials.gov registration no. NCT02229006 © RSNA, 2024.

PAR4 Antagonism in Patients With Coronary Artery Disease Receiving Antiplatelet Therapies.

BACKGROUND: BMS-986141 is a novel potent highly selective antagonist of PAR (protease-activated receptor) type 4. PAR4 antagonism has been demonstrated to reduce thrombus formation in isolation and in combination with factor Xa inhibition in high shear conditions in healthy people. We sought to determine whether PAR4 antagonism had additive antithrombotic effects in patients with coronary artery disease who were receiving antiplatelet therapy. METHODS: Forty-five patients with stable coronary heart disease and 10 healthy volunteers completed a phase 2a open-label 4-arm single-center study. Patients were allocated to 1 of 3 treatment arms for 7 days: (1) ticagrelor (90 mg BID), (2) aspirin (75 mg QD), or (3) the combination of ticagrelor and aspirin. Agonist-induced platelet aggregation, platelet activation, and ex vivo thrombus formation were measured before and 2 and 24 hours after a single oral 4-mg dose of BMS-986141 on the first study visit day in all participants. RESULTS: BMS-986141 demonstrated highly selective inhibition of PAR4-AP (agonist peptide)-induced platelet aggregation, P-selectin expression, and platelet-monocyte aggregate expression (P≤0.001 for all), which were unaffected by concomitant antiplatelet therapies. PAR4 antagonism reduced ex vivo thrombus area in high shear conditions in healthy volunteers (-21%; P=0.001) and in patients receiving ticagrelor alone (-28%; P=0.001), aspirin alone (-23%; P=0.018), or both in combination (-24%; P≤0.001). Plasma concentration of BMS-986141 correlated with PAR4-AP-induced platelet responses (P≤0.001 for all) and total thrombus area under high shear stress conditions (P≤0.01 for all). CONCLUSIONS: PAR4 antagonism has additive antithrombotic effects when used in addition to ticagrelor, aspirin, or their combination, in patients with stable coronary heart disease. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT05093790.

Quality of Reporting Using Good Reporting of A Mixed Methods Study Criteria in Chiropractic Mixed Methods Research: A Methodological Review.

OBJECTIVE: The purpose of this review was to examine the reporting in chiropractic mixed methods research using Good Reporting of A Mixed Methods Study (GRAMMS) criteria. METHODS: In this methodological review, we searched MEDLINE, Embase, CINAHL, and the Index to Chiropractic Literature from the inception of each database to December 31, 2020, for chiropractic studies reporting the use of both qualitative and quantitative methods or mixed qualitative methods. Pairs of reviewers independently screened titles, abstracts, and full-text studies, extracted data, and appraised reporting using the GRAMMS criteria and risk of bias with the Mixed Methods Appraisal Tool (MMAT). Generalized estimating equations were used to explore factors associated with reporting using GRAMMS criteria. RESULTS: Of 1040 citations, 55 studies were eligible for review. Thirty-seven of these 55 articles employed either a multistage or convergent mixed methods design, and, on average, 3 of 6 GRAMMS items were reported among included studies. We found a strong positive correlation in scores between the GRAMMS and MMAT instruments (r = 0.78; 95% CI, 0.66-0.87). In our adjusted analysis, publications in journals indexed in Web of Science (adjusted odds ratio = 2.71; 95% CI, 1.48-4.95) were associated with higher reporting using GRAMMS criteria. Three of the 55 studies fully adhered to all 6 GRAMMS criteria, 4 studies adhered to 5 criteria, 10 studies adhered to 4 criteria, and the remaining 38 adhered to 3 criteria or fewer. CONCLUSION: Our findings suggest that reporting in chiropractic mixed methods research using GRAMMS criteria was poor, particularly among studies with a higher risk of bias.

Noninvasive In Vivo Thrombus Imaging in Patients With Ischemic Stroke or Transient Ischemic Attack-Brief Report.

BACKGROUND: 18F-GP1 is a novel positron-emitting radiotracer that is highly specific for activated platelets and thrombus. In a proof-of-concept study, we aimed to determine its potential clinical application in establishing the role and origin of thrombus in ischemic stroke. METHODS: Eleven patients with recent ischemic stroke (n=9) or transient ischemic attack (n=2) underwent 18F-GP1 positron emission tomography and computed tomography angiography at a median of 11 (range, 2-21) days from symptom onset. 18F-GP1 uptake (maximum target-to-background ratio) was assessed in the carotid arteries and brain. RESULTS: 18F-GP1 uptake was identified in 10 of 11 patients: 4 in the carotid arteries only, 3 in the brain only, and 3 in both the brain and carotid arteries. In those with carotid uptake, 4 participants had >50% stenosis and 3 had nonstenotic disease. One case had bilateral stenotic disease (>70%), but only the culprit carotid artery demonstrated 18F-GP1 uptake. The average uptake was higher in the culprit (median maximum target-to-background ratio, 1.55 [interquartile range, 1.26-1.82]) compared with the contralateral nonculprit carotid artery (maximum target-to-background ratio, 1.22 [1.19-1.6]). In those with brain 18F-GP1 uptake (maximum target-to-background ratio, 6.45 [4.89-7.65]), areas of acute infarction on computed tomography correlated with brain 18F-GP1 uptake in 6 cases. Ex vivo autoradiography of postmortem infarcted brain tissue showed focal uptake corresponding to intraluminal thrombus within the culprit vessel and downstream microvasculature. There was also evidence of diffuse uptake within some of the infarcted brain tissue reflecting parenchymal petechial hemorrhage. CONCLUSIONS: 18F-GP1 positron emission tomography and computed tomography angiography is a novel noninvasive method of identifying in vivo cerebrovascular thrombosis, which holds major promise in understanding the role and origin of thrombosis in stroke. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT03943966.

Biosensor development for single-cell detection of glucuronate.

Recent work in biosensors has shown promise to enable high throughput searches through large genetic libraries. However, just as physiological limitations and lack of in-depth mechanistic knowledge can prevent us from achieving high titers in microbial systems; similar roadblocks can appear in the application of biosensors. Here, we characterized a previously developed transcription-factor (ExuR) based galacturonate biosensor for its other cognate ligand, glucuronate. Though we saw an ideal response to glucuronate from the biosensor in controlled and ideal experimental circumstances, these results began to deviate from a well-behaved system when we explored the application of the sensor to different MIOX homologs. Through modifications to circuit architecture and culture conditions, we were able to decrease this variation and use these more optimal conditions to apply the biosensor for the separation of two closely related MIOX homologs. ONE-SENTENCE SUMMARY: In this work, a transcription-factor biosensor was investigated for its potential to screen a library of myo -inositol oxygenase variants while seeking to mitigate the impact the production pathway appeared to have on the biosensor.

Aortic sodium [18F]fluoride uptake following endovascular aneurysm repair.

OBJECTIVE: In patients with abdominal aortic aneurysms, sodium [18F]fluoride positron emission tomography identifies aortic microcalcification and disease activity. Increased uptake is associated with aneurysm expansion and adverse clinical events. The effect of endovascular aneurysm repair (EVAR) on aortic disease activity and sodium [18F]fluoride uptake is unknown. This study aimed to compare aortic sodium [18F]fluoride uptake before and after treatment with EVAR. METHODS: In a preliminary proof-of-concept cohort study, preoperative and post-operative sodium [18F]fluoride positron emission tomography-computed tomography angiography was performed in patients with an infrarenal abdominal aortic aneurysm undergoing EVAR according to current guideline-directed size treatment thresholds. Regional aortic sodium [18F]fluoride uptake was assessed using aortic microcalcification activity (AMA): a summary measure of mean aortic sodium [18F]fluoride uptake. RESULTS: Ten participants were recruited (76±6 years) with a mean aortic diameter of 57±2 mm at time of EVAR. Mean time from EVAR to repeat scan was 62±21 months. Prior to EVAR, there was higher abdominal aortic AMA when compared with the thoracic aorta (AMA 1.88 vs 1.2; p<0.001). Following EVAR, sodium [18F]fluoride uptake was markedly reduced in the suprarenal (ΔAMA 0.62, p=0.03), neck (ΔAMA 0.72, p=0.02) and body of the aneurysm (ΔAMA 0.69, p=0.02) while it remained unchanged in the thoracic aorta (ΔAMA 0.11, p=0.41). CONCLUSIONS: EVAR is associated with a reduction in AMA within the stented aortic segment. This suggests that EVAR can modify aortic disease activity and aortic sodium [18F]fluoride uptake is a promising non-invasive surrogate measure of aneurysm disease activity.

Early postoperative complications following tracheotomy: Does suturing technique influence outcomes?

Introduction: Tracheotomy is one of the most commonly performed procedure by otolaryngologists, but no consensus exists on the effect of suturing techniques on postoperative complications. Stay sutures and Bjork flaps are utilized frequently for securing the tracheal incision to the neck skin in order to create a tract for recannulation. Methods: Retrospective cohort study of tracheotomies performed by Otolaryngology-Head and Neck Surgery providers (May 2014 to August 2020) was conducted to determine the effect of suturing technique on postoperative complications and patient outcomes. Patient demographics, medical comorbidities, indication for tracheostomy, and postoperative complications were analyzed with a statistical alpha set of .05. Results: Out of 1395 total tracheostomies performed at our institution during the study period, 518 met inclusion criteria for this study. Three hundred and seventeen tracheostomies were secured by utilizing a Bjork flap, while 201 were secured with up and down stay sutures. Neither technique was noted to be more commonly associated with tracheal bleeding, infection, mucus plugging, pneumothorax, or false passage of the tracheostomy tube. One mortality was noted following decannulation during the study period. Conclusion: Though various techniques exist; adverse outcomes are not associated with the manner in which a new tracheostomy stoma is secured. Medical comorbidities and the indications for tracheostomy likely play a more significant role in postoperative outcomes and complications. Level of evidence: Level 3.

Evaluating Natural Gas Emissions from Pneumatic Controllers from Upstream Oil and Gas Facilities in West Virginia.

In April of 2018, an optical gas imaging (OGI) and full flow sampler (FFS) emissions measurement study of pneumatic controllers (PCs) was conducted at 15 oil and natural gas production sites in West Virginia. The objective of the study was to identify and characterize PC systems with excessive emissions caused by maintenance issues or nonoptimized process conditions. A total of 391 PC systems were found on the sites and all were classified by the operator as snap-acting (on/off) intermittent venting PCs (IPCs) that should exhibit little gas release while the PC is closed between actuation events. The population was comprised of two groups, 259 infrequently actuating, lower emitting (LE) IPCs and 132 gas processing unit (GPU) liquid level IPCs and associated dump valve actuators that vent more frequently and have larger emission volumes. Using a PC-specific OGI inspection protocol with an assumed whole gas OGI detection threshold of 2.0 scfh, only 2 out of 259 LE-IPCs exhibited OGI detectable emissions indicating good inspection and maintenance practices for this category. Due to combined (ganged) GPU exhaust vents, the OGI inspection of the GPU liquid level IPCs was comparatively less informative and determination of single component IPC emissions by the FFS was more difficult. The time resolved FFS measurements of GPU IPCs defined three categories of operation: one that indicated proper function and two associated with higher emissions that may result from an IPC maintenance or process issues. The overall GPU IPC emission distribution was heavy tailed, with a median value of 12.8 scfh, similar to the 13.5 scfh whole gas IPC emission factor (EF). Total emissions were dominated by non-optimal temporal profile high-emitter IPC cases with the top 20% of IPC systems accounting for between 51.3% and 70.7% of GPU liquid level IPC emissions by volume. The uncertainty in the estimate was due to the ganged nature of the GPU exhaust vents. The highest GPU IPC emission came from a single malfunctioning unit with a measured whole gas value of 157 scfh. Up to six IPCs exceeded 100 scfh. An analysis of FFS emission measurements compared to liquids production per IPC unit employed indicated that production sites operating at a high level of liquids production test the limits of the site engineering, likely resulting in higher IPC emissions. Overall, this study found that the LE-IPCs with OGI-verified low closed bleed rates may emit well below the IPC EF while GPU liquid level IPC systems are likely well represented by the current IPC EF. IPCs that are experiencing a maintenance or process issue or that are operating at sites with a very high product throughput per IPC employed can emit at rates exceeding ten times IPC EF.

Noninvasive In Vivo Coronary Artery Thrombus Imaging.

BACKGROUND: The diagnosis and management of myocardial infarction are increasingly complex, and establishing the presence of intracoronary thrombosis has major implications for both the classification and treatment of myocardial infarction. OBJECTIVES: The aim of this study was to investigate whether positron emission tomographic (PET) and computed tomographic (CT) imaging could noninvasively detect in vivo thrombus formation in human coronary arteries using a novel glycoprotein IIb/IIIa receptor antagonist-based radiotracer, 18F-GP1. METHODS: In a single-center observational case-control study, patients with or without acute myocardial infarction underwent coronary 18F-GP1 PET/CT angiography. Coronary artery 18F-GP1 uptake was assessed visually and quantified using maximum target-to-background ratios. RESULTS: 18F-GP1 PET/CT angiography was performed in 49 patients with and 50 patients without acute myocardial infarction (mean age: 61 ± 9 years, 75% men). Coronary 18F-GP1 uptake was apparent in 39 of the 49 culprit lesions (80%) in patients with acute myocardial infarction. False negative results appeared to relate to time delays to scan performance and low thrombus burden in small-caliber distal arteries. On multivariable regression analysis, culprit vessel status was the only independent variable associated with higher 18F-GP1 uptake. Extracoronary cardiac 18F-GP1 findings included a high frequency of infarct-related intramyocardial uptake (35%) as well as left ventricular (8%) or left atrial (2%) thrombus. CONCLUSIONS: Coronary 18F-GP1 PET/CT angiography is the first noninvasive selective technique to identify in vivo coronary thrombosis in patients with acute myocardial infarction. This novel approach can further define the role and location of thrombosis within the heart and has the potential to inform the diagnosis, management, and treatment of patients with acute myocardial infarction. (In-Vivo Thrombus Imaging With 18F-GP1, a Novel Platelet PET Radiotracer [iThrombus]; NCT03943966).

Accelerated Evolution of Cytochrome c in Higher Primates, and Regulation of the Reaction between Cytochrome c and Cytochrome Oxidase by Phosphorylation.

Cytochrome c (Cc) underwent accelerated evolution from the stem of the anthropoid primates to humans. Of the 11 amino acid changes that occurred from horse Cc to human Cc, five were at Cc residues near the binding site of the Cc:CcO complex. Single-point mutants of horse and human Cc were made at each of these positions. The Cc:CcO dissociation constant KD of the horse mutants decreased in the order: T89E > native horse Cc > V11I Cc > Q12M > D50A > A83V > native human. The largest effect was observed for the mutants at residue 50, where the horse Cc D50A mutant decreased KD from 28.4 to 11.8 µM, and the human Cc A50D increased KD from 4.7 to 15.7 µM. To investigate the role of Cc phosphorylation in regulating the reaction with CcO, phosphomimetic human Cc mutants were prepared. The Cc T28E, S47E, and Y48E mutants increased the dissociation rate constant kd, decreased the formation rate constant kf, and increased the equilibrium dissociation constant KD of the Cc:CcO complex. These studies indicate that phosphorylation of these residues plays an important role in regulating mitochondrial electron transport and membrane potential ΔΨ.

Risk of bias in chiropractic mixed methods research: a secondary analysis of a meta-epidemiological review.

Objective: To examine the risk of bias in chiropractic mixed methods research. Methods: We performed a secondary analysis of a meta-epidemiological review of chiropractic mixed methods studies. We assessed risk of bias with the Mixed Methods Appraisal Tool (MMAT) and used generalized estimating equations to explore factors associated with risk of bias. Results: Among 55 eligible studies, a mean of 62% (6.8 [2.3]/11) of MMAT items were fulfilled. In our adjusted analysis, studies published since 2010 versus pre-2010 (adjusted odds ratio [aOR] = 2.26; 95% confidence interval [CI], 1.39 to 3.68) and those published in journals with an impact factor versus no impact factor (aOR = 2.21; 95% CI, 1.33 to 3.68) were associated with lower risk of bias. Conclusion: Our findings suggest opportunities for improvement in the quality of conduct among published chiropractic mixed methods studies. Author compliance with the MMAT criteria may reduce methodological bias in future mixed methods research.

Objectif: examiner le risque de biais dans la recherche sur les méthodes mixtes chiropratiques. Méthodologie: nous avons effectué une analyse secondaire d'un examen méta-épidémiologique d'études de méthodes mixtes chiropratiques. Nous avons examiné le risque de biais avec The Mixed Methods Appraisal Tool, MMAT (l'outil d'évaluation des méthodes mixtes), et utilisé des équations d'estimation généralisées pour explorer les facteurs associés au risque de biais. Résultats: parmi 55 études admissibles, une moyenne de 62 % (6,8 [2,3]/11) des items du MMAT ont été remplis. Dans notre analyse ajustée, les études publiées depuis 2010 versus celles d'avant 2010 (rapport de cotes [aOR] ajusté = 2,26; intervalle de confiance [IC] à 95 %, 1,39 à 3,68), et celles publiées dans des revues avec un indice de citations versus aucun indice de citations (aOR = 2,21; IC à 95 %, 1,33 à 3,68) étaient associées à un risque de biais plus faible. Conclusion: nos résultats suggèrent des opportunités d'amélioration de la qualité de la conduite parmi les études publiées sur les méthodes mixtes chiropratiques. La conformité des auteurs aux critères MMAT peut réduire les biais méthodologiques dans les futures recherches sur les méthodes mixtes.

Quantifying sodium [18F]fluoride uptake in abdominal aortic aneurysms.

BACKGROUND: Aortic microcalcification activity is a recently described method of measuring aortic sodium [18F]fluoride uptake in the thoracic aorta on positron emission tomography. In this study, we aimed to compare and to modify this method for use within the infrarenal aorta of patients with abdominal aortic aneurysms. METHODS: Twenty-five patients with abdominal aortic aneurysms underwent an sodium [18F]fluoride positron emission tomography and computed tomography scan. Maximum and mean tissue-to-background ratios (TBR) and abdominal aortic microcalcification activity were determined following application of a thresholding and variable radius method to correct for vertebral sodium [18F]fluoride signal spill-over and the nonlinear changes in aortic diameter, respectively. Agreement between the methods, and repeatability of these approaches were assessed. RESULTS: The aortic microcalcification activity method was much quicker to perform than the TBR method (14 versus 40 min, p < 0.001). There was moderate-to-good agreement between TBR and aortic microcalcification activity measurements for maximum (interclass correlation co-efficient, 0.67) and mean (interclass correlation co-efficient, 0.88) values. These correlations sequentially improved with the application of thresholding (intraclass correlation coefficient 0.93, 95% confidence interval 0.89-0.95) and variable diameter (intraclass correlation coefficient 0.97, 95% confidence interval 0.94-0.99) techniques. The optimised method had good intra-observer (mean 1.57 ± 0.42, bias 0.08, co-efficient of repeatability 0.36 and limits of agreement - 0.43 to 0.43) and inter-observer (mean 1.57 ± 0.42, bias 0.08, co-efficient of repeatability 0.47 and limits of agreement - 0.53 to 0.53) repeatability. CONCLUSIONS: Aortic microcalcification activity is a quick and simple method which demonstrates good intra-observer and inter-observer repeatabilities and provides measures of sodium [18F]fluoride uptake that are comparable to established methods.

Microcalcification and Thoracic Aortopathy: A Window Into Disease Severity.

BACKGROUND: Patients with thoracic aortopathy are at increased risk of catastrophic aortic dissection, carrying with it substantial mortality and morbidity. Although granular medial calcinosis (medial microcalcification) has been associated with thoracic aortopathy, its relationship to disease severity has yet to be established. METHODS: One hundred one thoracic aortic specimens were collected from 57 patients with thoracic aortopathy and 18 control subjects. Standardized histopathologic scores, immunohistochemistry, and nanoindentation (tissue elastic modulus) were compared with the extent of microcalcification on von Kossa histology and 18F-sodium fluoride autoradiography. RESULTS: Microcalcification content was higher in thoracic aortopathy samples with mild (n=28; 6.17 [2.71-10.39]; P≤0.00010) or moderate histopathologic degeneration (n=30; 3.74 [0.87-11.80]; P<0.042) compared with control samples (n=18; 0.79 [0.36-1.90]). Alkaline phosphatase (n=26; P=0.0019) and OPN (osteopontin; n=26; P=0.0045) staining were increased in tissue with early aortopathy. Increasingly severe histopathologic degeneration was related to reduced microcalcification (n=82; Spearman ρ, -0.51; P<0.0001)-a process closely linked with elastin loss (n=82; Spearman ρ, -0.43; P<0.0001) and lower tissue elastic modulus (n=28; Spearman ρ, 0.43; P=0.026).18F-sodium fluoride autoradiography demonstrated good correlation with histologically quantified microcalcification (n=66; r=0.76; P<0.001) and identified areas of focal weakness in vivo. CONCLUSIONS: Medial microcalcification is a marker of aortopathy, although progression to severe aortopathy is associated with loss of both elastin fibers and microcalcification.18F-sodium fluoride positron emission tomography quantifies medial microcalcification and is a feasible noninvasive imaging modality for identifying aortic wall disruption with major translational promise.

Thoracic Aortic 18F-Sodium Fluoride Activity and Ischemic Stroke in Patients With Established Cardiovascular Disease.

BACKGROUND: Aortic atherosclerosis represents an important contributor to ischemic stroke risk. Identifying patients with high-risk aortic atheroma could improve preventative treatment strategies for future ischemic stroke. OBJECTIVES: The purpose of this study was to investigate whether thoracic 18F-sodium fluoride positron emission tomography (PET) could improve the identification of patients at the highest risk of ischemic stroke. METHODS: In a post hoc observational cohort study, we quantified thoracic aortic and coronary 18F-sodium fluoride activity in 461 patients with stable cardiovascular disease undergoing PET combined with computed tomography (CT). Progression of atherosclerosis was assessed by change in aortic and coronary CT calcium volume. Clinical outcomes were determined by the occurrence of ischemic stroke and myocardial infarction. We compared the prognostic utility of 18F-sodium fluoride activity for predicting stroke to clinical risk scores and CT calcium quantification using survival analysis and multivariable Cox regression. RESULTS: After 12.7 ± 2.7 months, progression of thoracic aortic calcium volume correlated with baseline thoracic aortic 18F-sodium fluoride activity (n = 140; r = 0.31; P = 0.00016). In 461 patients, 23 (5%) patients experienced an ischemic stroke and 32 (7%) a myocardial infarction after 6.1 ± 2.3 years of follow-up. High thoracic aortic 18F-sodium fluoride activity was strongly associated with ischemic stroke (HR: 10.3 [95% CI: 3.1-34.8]; P = 0.00017), but not myocardial infarction (P = 0.40). Conversely, high coronary 18F-sodium fluoride activity was associated with myocardial infarction (HR: 4.8 [95% CI: 1.9-12.2]; P = 0.00095) but not ischemic stroke (P = 0.39). In a multivariable Cox regression model including imaging and clinical risk factors, thoracic aortic 18F-sodium fluoride activity was the only variable associated with ischemic stroke (HR: 8.19 [95% CI: 2.33-28.7], P = 0.0010). CONCLUSIONS: In patients with established cardiovascular disease, thoracic aortic 18F-sodium fluoride activity is associated with the progression of atherosclerosis and future ischemic stroke. Arterial 18F-sodium fluoride activity identifies localized areas of atherosclerotic disease activity that are directly linked to disease progression and downstream regional clinical atherothrombotic events. (DIAMOND-Dual Antiplatelet Therapy to Reduce Myocardial Injury [DIAMOND], NCT02110303; Study Investigating the Effect of Drugs Used to Treat Osteoporosis on the Progression of Calcific Aortic Stenosis [SALTIRE II], NCT02132026; Novel Imaging Approaches To Identify Unstable Coronary Plaques, NCT01749254; and Role of Active Valvular Calcification and Inflammation in Patients With Aortic Stenosis, NCT01358513).

Bypass Grafting and Native Coronary Artery Disease Activity.

OBJECTIVES: The aim of this study was to describe the potential of 18F-sodium fluoride (18F-NaF) positron emission tomography (PET) to identify graft vasculopathy and to investigate the influence of coronary artery bypass graft (CABG) surgery on native coronary artery disease activity and progression. BACKGROUND: As well as developing graft vasculopathy, CABGs have been proposed to accelerate native coronary atherosclerosis. METHODS: Patients with established coronary artery disease underwent baseline 18F-NaF PET, coronary artery calcium scoring, coronary computed tomographic angiography, and 1-year repeat coronary artery calcium scoring. Whole-vessel coronary microcalcification activity (CMA) on 18F-NaF PET and change in calcium scores were quantified in patients with and without CABG surgery. RESULTS: Among 293 participants (mean age 65 ± 9 years, 84% men), 48 (16%) underwent CABG surgery 2.7 years [IQR: 1.4-10.4 years] previously. Although all arterial and the majority (120 of 128 [94%]) of vein grafts showed no 18F-NaF uptake, 8 saphenous vein grafts in 7 subjects had detectable CMA. Bypassed native coronary arteries had 3 times higher CMA values (2.1 [IQR: 0.4-7.5] vs 0.6 [IQR: 0-2.7]; P < 0.001) and greater progression of 1-year calcium scores (118 Agatston unit [IQR: 48-194 Agatston unit] vs 69 [IQR: 21-142 Agatston unit]; P = 0.01) compared with patients who had not undergone CABG, an effect confined largely to native coronary plaques proximal to the graft anastomosis. In sensitivity analysis, bypassed native coronary arteries had higher CMA (2.0 [IQR: 0.4-7.5] vs 0.8 [IQR: 0.3-3.2]; P < 0.001) and faster disease progression (24% [IQR: 16%-43%] vs 8% [IQR: 0%-24%]; P = 0.002) than matched patients (n = 48) with comparable burdens of coronary artery disease and cardiovascular comorbidities in the absence of bypass grafting. CONCLUSIONS: Native coronary arteries that have been bypassed demonstrate increased disease activity and more rapid disease progression than nonbypassed arteries, an observation that appears independent of baseline atherosclerotic plaque burden. Microcalcification activity is not a dominant feature of graft vasculopathy.

Model of an Advanced Practice Provider-Led Head and Neck Cancer Survivorship Clinic: Evaluation of a 4-Year Experience.

OBJECTIVE: To report the efficacy and safety of an advanced practice provider-led head and neck cancer survivorship clinic. STUDY DESIGN: Retrospective chart review. SETTING: Tertiary academic medical center. METHODS: Patients were enrolled into the survivorship clinic after undergoing 1-year follow-up with the primary head and neck surgeon. Those enrolled between December 2016 and October 2020 were retrospectively reviewed for diagnosis, staging, pattern of recurrence, visit frequency, and compliance. Surgical respectability of recurrent disease was used as a surrogate for timely diagnosis. RESULTS: An overall 570 patients were followed within the survivorship clinic. The mean length of follow-up was 13.6 months. Mucosal primaries represented 72.6% of patients. A majority of the primary malignancies were squamous cell carcinoma (77.7%). The most common primary subsites were the oropharynx (26.7%), oral cavity (25.1%), cutaneous (17.0%), and larynx (15.3%). Recurrence was detected in 50 patients (8.8%): 26 local, 12 regional, and 14 distant. Two patients had multiple synchronous recurrences. Twelve (2.1%) second primary cancers were detected. Of the 36 cases of locoregional recurrence, 32 (88.9%) were deemed amenable to salvage surgical intervention, with or without adjuvant therapy. Negative margins were obtained in 21 of the 23 (91.3%) local recurrences that underwent salvage resection. CONCLUSION: Advanced practice provider-based surveillance of head and neck cancer, without risk stratification, appears to be a sound model but needs further prospective evaluation. Consistent with literature, 88.9% of patients with locoregional recurrence were candidates for curative-intent salvage surgery, emphasizing that recurrences are identified in a timely fashion.

Standardizing HIV post-exposure prophylaxis in the emergency department following sexual assault.

OBJECTIVES: A standardized non-occupational post-exposure prophylaxis (nPEP) programme was implemented to improve guideline compliance for treatment of post-sexual assault patients within an emergency department (ED). METHODS: A single-centre, retrospective, observational study of adult patients evaluated in the ED for sexual assault was performed following nPEP programme implementation. A comprehensive nPEP programme consisting of a standardized order set, real-time multidisciplinary consultation, on-site pharmacy and close post-discharge follow-up was implemented between July 2017 and June 2018. Laboratory, treatment, vaccination, prescription and follow-up data during the pre- (July 2016 to June 2017) and post-intervention (July 2018 to August 2019) periods were compared. RESULTS: Of the 147 post-sexual assault patients included in this study (59 pre-intervention, 88 post-intervention), 133 (90.5%) were eligible for nPEP. Patient demographics and rate of those eligible for nPEP were similar in both cohorts. Antiretroviral therapy (ART) was offered (72.2% vs. 100%; p < 0.005) and ultimately prescribed (51.9% vs. 86.1%; p < 0.005) more frequently following nPEP programme implementation. Patients were more likely to have appropriate screening for renal function, liver function, pregnancy, syphilis, hepatitis B, hepatitis C and HIV in the post-intervention period (all p < 0.005). Hepatitis B vaccination was more commonly administered post-intervention (8.5% vs. 22.7%; p < 0.024). In-person 28-day follow-up was rare in both pre- (3.5%) and post-intervention (11.3%) cohorts (p = 0.278). CONCLUSIONS: Implementation of a comprehensive nPEP programme resulted in improved guideline compliance with more frequent and appropriate ART administration. Recommended screening laboratories and hepatitis B vaccinations were more commonly performed, but in-person follow-up remained low. The nPEP programmes should be implemented to standardize efforts that decrease the risk of HIV transmission.

Hypertension in China: burdens, guidelines and policy responses: a state-of-the-art review.

Hypertension is a leading risk factor of cardiovascular disease and it is becoming increasingly prevalent globally. Correspondingly, the Chinese government and public health institutions have issued a series of policy documents and guidelines for hypertension. However, no comprehensive review of such documents has been conducted. Hence, this review aims to provide an up-to-date and comprehensive assessment of not only the disease burden, but also hypertension management policies and guidelines in China. A total of 15 epidemiological studies based on national population surveys, 15 Chinese Hypertension Guidelines, and seven policy documents were identified. We found a larger burden of hypertension in men, while the awareness, treatment, and control rates have remained low in both sexes. The ranges of hypertension prevalence, awareness, treatment, and control rate among hypertensive patients were 18.0-44.7%, 23.6-56.2%, 14.2-48.5%, and 4.2-30.1% respectively. Chinese hypertension guidelines provide evidence-based instructions to healthcare practitioners over hypertension management in which primary healthcare is increasingly emphasized. Finally, the policy documents set national goals for hypertension management and standardized the services provided in primary healthcare. The findings highlight the importance of integrating new guidelines into hypertension management provided by primary healthcare practitioners and the need to evaluate the implementation of guidelines and policies.