Effectiveness of a new 3D printed simulator for mitral transcatheter edge-to-edge repair in enhancing the confidence and procedural skills of the operator.

BACKGROUND: . Mitral transcatheter edge-to-edge repair (m-TEER) is a minimally invasive procedure for treating mitral regurgitation (MR). m-TEER is a highly technical procedure, and a steep learning curve needs to be overcome for operators to ensure optimal patient outcomes and minimise procedural complications. Training via online simulation and observation of procedures is not sufficient to establish operator confidence; thus, advanced hands-on training modalities need to be explored and developed. METHODS: . In this study, a novel anatomical simulator for m-TEER training was evaluated in comparison to a standard model. The proposed simulator resembled the anatomical features of the right and left atrium, left ventricle and mitral valve apparatus. Participants in the questionnaire (n = 18) were recruited across 4 centres in London with (n = 8) and without (n = 10) prior experience in m-TEER. Participants were asked to simulate procedures on both an idealised, routinely used simulator and the newly proposed anatomical model. The questionnaire was designed to assess (i) participants' confidence before and after training and (ii) the realism of the model in the context of the m-TEER procedure. The results of the questionnaires were collected, and statistical analysis (t-test) was performed. RESULTS: . Both models were equally beneficial in increasing operator confidence before and after the simulation of the intervention (P = 0.43). However, increased confidence after training with the anatomical model was recorded (P = 0.02). Participants with prior experience with m-TEER therapy were significantly more confident about the procedure after training with the anatomical model than participants who had no prior experience (P = 0.002). On average, all participants thought that the anatomical model was effective as a training simulator (P = 0.013) and should be integrated into routine training (P = 0.015)). Participants with experience thought that the anatomical model was more effective at reproducing the m-TEER procedure than the idealised model (P = 0.03). CONCLUSIONS: . This study showed how a more realistic simulator can be used to improve the effectiveness of m-TEER procedural training. Such pilot results suggest planning future and large investigations to evaluate improvements in clinical practice.

A bioactive supramolecular and covalent polymer scaffold for cartilage repair in a sheep model.

Regeneration of hyaline cartilage in human-sized joints remains a clinical challenge, and it is a critical unmet need that would contribute to longer healthspans. Injectable scaffolds for cartilage repair that integrate both bioactivity and sufficiently robust physical properties to withstand joint stresses offer a promising strategy. We report here on a hybrid biomaterial that combines a bioactive peptide amphiphile supramolecular polymer that specifically binds the chondrogenic cytokine transforming growth factor ß-1 (TGFß-1) and crosslinked hyaluronic acid microgels that drive formation of filament bundles, a hierarchical motif common in natural musculoskeletal tissues. The scaffold is an injectable slurry that generates a porous rubbery material when exposed to calcium ions once placed in cartilage defects. The hybrid material was found to support in vitro chondrogenic differentiation of encapsulated stem cells in response to sustained delivery of TGFß-1. Using a sheep model, we implanted the scaffold in shallow osteochondral defects and found it can remain localized in mechanically active joints. Evaluation of resected joints showed significantly improved repair of hyaline cartilage in osteochondral defects injected with the scaffold relative to defects injected with the growth factor alone, including implantation in the load-bearing femoral condyle. These results demonstrate the potential of the hybrid biomimetic scaffold as a niche to favor cartilage repair in mechanically active joints using a clinically relevant large-animal model.

Comparison of stroke process measures and clinical outcomes between English and Non-English preferring patients.

BACKGROUND: In the United States, limited English proficiency may reduce the quality of care and worsen outcomes after stroke. The aim was to compare stroke process measures and clinical outcomes between English preferring and non-English preferring stroke patients. METHODS/MATERIALS: This single-center retrospective cohort study evaluated patients from one United States hospital with acute ischemic stroke between July 2013 and June 2022. The primary outcomes were defect-free care, a composite of 7 stroke process measures, and independent ambulation at hospital discharge. Multivariate logistic regression models quantified the association between language preference and outcomes. Secondary outcomes included individual components of defect-free care, discharge modified Rankin scale, and discharge disposition. RESULTS: There were 4,030 patients with acute ischemic stroke identified, of which 2,965 were matched with language data from the electronic medical record. There were 373 non-English preferring patients, among which 76.9% preferred Spanish and 23.1% were non-English, non-Spanish preferring. In the multivariable model, there was no significant association between non-English preference and defect-free care (OR=0.64, 95% CI=0.26-1.59) or independent ambulation at discharge (OR=0.89, 95% CI=0.67-1.17). When compared to Spanish preferring patients, non-English, non-Spanish preferring patients had more severe strokes (P<0.001) but there was no difference in defect-free care or independent ambulation after adjustment. CONCLUSION: Our results suggest that process and clinical outcomes are similar regardless of language preference; although, our data are limited by small numbers of non-English, non-Spanish preferring patients. Additional research is needed among this population.

Case report: Blood-transfusion induced posterior reversible encephalopathy syndrome.

Posterior reversible encephalopathy syndrome (PRES) is an increasingly recognized clinical entity associated with a variety of medical conditions. It is commonly considered in the presentation of uncontrolled, severe hypertension. However, more recently, it has been described in the setting of blood transfusion, particularly in those with chronic anemia, even in the absence of severe hypertension. We describe a patient who presented to the emergency department 12 days after large blood transfusion for severe, chronic anemia with headache, vision loss, expressive aphasia and a change in mental status, with only mild blood pressure elevation, who was ultimately diagnosed with PRES and refractory non-convulsive status epilepticus. Emergency physicians are often the first to initiate blood transfusion for those with a low hemoglobin. Therefore, it is prudent to proceed with caution in transfusing those with chronic anemia. It is also important for the emergency physician to keep PRES on the differential for those presenting with a neurologic complaint after correction of their chronic anemia, even in the absence of severe hypertension.

Infarct density defined by ADC threshold is associated with long-term functional outcome after endovascular thrombectomy.

OBJECTIVES: Endovascular thrombectomy (EVT) dramatically improves clinical outcomes, but the reduction in final infarct volume only accounts for 10-15 % of the treatment benefit. We aimed to develop a novel MRI-ADC-based metric that quantify the degree of tissue injury to test the hypothesis that it outperforms infarct volume in predicting long-term outcome. MATERIALS AND METHODS: A single-center cohort consisted of consecutive acute stroke patients with anterior circulation large vessel occlusion, successful recanalization via EVT (mTICI ≥2b), and MRI of the brain between 12 h and 7 days post-EVT. Imaging was processed via RAPID software. Final infarct volume was based on the traditional ADC <620 threshold. Logistic regression quantified the association of lesion volumes and good outcome (90-day modified Rankin Scale ≤2) at a range of lower ADC thresholds (<570, <520, and <470). Infarct density was calculated as the percentage of the final infarct volume below the ADC threshold with the greatest effect size. Univariate and multivariate logistic regression quantified the association between imaging/clinical metrics and functional outcome. RESULTS: 120 patients underwent MRI after successful EVT. Lesion volume based on the ADC threshold <470 had the strongest association with good outcome (OR: 0.81 per 10 mL; 95 % CI: 0.66-0.99). In a multivariate model, infarct density (<470/<620 * 100) was independently associated with good outcome (aOR 0.68 per 10 %; 95 % CI: 0.49-0.95), but final infarct volume was not (aOR 0.98 per 10 mL; 95 % CI: 0.85-1.14). CONCLUSIONS: Infarct density after EVT is more strongly associated with long-term clinical outcome than infarct volume.

Transcatheter Aortic Valve Replacement With the Navitor System: Real-World United Kingdom Experience.

The Navitor transcatheter heart valve (THV) is the latest iteration of the Portico self-expanding valve system. Early prospective studies have shown promising outcomes, however, there is a lack of complementary 'real-world' data. This study aimed to assess early safety and efficacy outcomes of the Navitor THV using registry data from 6 high-volume United Kingdom transcatheter aortic valve replacement (TAVR) centers. Demographic, procedural, and in-hospital outcome data were retrieved from 6 United Kingdom centers. The primary safety end point was 30-day mortality. Primary efficacy end points were procedural success, mean aortic gradient, and ≥moderate paravalvular leak. Secondary end points included rates of new permanent pacemaker implantation, stroke, and vascular injury. A total of 574 patients (mean age 83.4 years; 54.5% female) underwent Navitor TAVR between January 2020 and May 2023. The 30-day mortality in this patient cohort was 1.6%. Procedural success was 98.1%, mean echo-derived gradient post-TAVR was 7.7 ± 4.8 mm Hg (95% confidence interval [CI] 7.2 to 8.3, p <0.001) and 5.1% of patients had ≥moderate paravalvular leak (sample proportion estimate [p̂] = 0.051, 95% CI [0.035, 0.073], p <0.001). New permanent pacemaker implantation to discharge was required in 11% (p̂ = 0.119, 95% CI 0.088 to 0.158, p <0.001), stroke occurred in 1.2% of patients (p̂ = 0.017, 95% CI 0.006 to 0.036, p <0.001) and significant vascular injury in 1.6% (p̂ = 0.014, 95% CI 0.005 to 0.032, p <0.001). In conclusion, early procedural outcomes with Navitor TAVR compare favorably to new-generation THVs. Procedural success was high with a low incidence of complications.

Contrast Volume-to-Estimated Glomerular Filtration Rate Ratio as a Predictor of Short-Term Outcomes Following Transcatheter Aortic Valve Implantation.

Background/Objectives: Contrast-induced acute kidney injury (AKI) is associated with early mortality and adverse events. However, in the setting of transcatheter aortic valve implantation (TAVI), previous literature has failed to establish a correlation between the absolute volume of contrast media administered and mortality. We aimed to investigate the impact of contrast volume administered normalised to estimated glomerular filtration rate (CV/eGFR) on the development of AKI and on 30-day all-cause mortality in TAVI patients. Methods: We retrospectively analysed a cohort of 1150 patients who underwent TAVI at our unit between 2015 and 2018. Results: Follow-up was complete for 1064 patients. There were 23 deaths within the follow-up period and 76 cases of AKI, 9 of which required new renal replacement therapy (RRT). Receiver-operating characteristic (ROC) curve analysis showed fair discrimination for 30-day all-cause mortality at a CV/eGFR ratio of 3.6 (area under the ROC curve (AUC) 0.671). Of patients in whom CV data were available, 86.0% (n = 757) had a CV/eGFR < 3.6 and 14.0% (n = 123) had a CV/eGFR ≥ 3.6. In multivariate logistic regression analysis, CV/eGFR ≥ 3.6 was the strongest predictor of 30-day all-cause mortality (odds ratio 5.06, 95% confidence interval [1.61-15.7], p = 0.004). Other independent predictors were procedural urgency (3.28 [1.04-10.3], p = 0.038) and being under general anaesthesia (4.81 [1.10-17.3], p = 0.023). CV/eGFR ≥ 3.6 was also independently associated with significantly increased odds of AKI (2.28 [1.20-4.17], p = 0.009) alongside significant non-left main stem coronary artery disease (2.56 [1.45-4.66], p = 0.001), and diabetes (1.82 [1.03-3.19], p = 0.037). In supplementary ROC curve analysis, a similar CV/eGFR cut point of 3.6 was found to be an excellent predictor for new RRT (AUC 0.833). Conclusions: In conclusion, a CV/eGFR ≥ 3.6 post-TAVI was found to be a strong predictor of 30-day mortality and AKI. The maximum contrast volume that can be safely administered in each patient without significantly increasing the risk of mortality and AKI can be calculated using this ratio.

Regional Distribution of Extracellular Volume Quantified by Cardiac CT in Aortic Stenosis: Insights Into Disease Mechanisms and Impact on Outcomes.

BACKGROUND: Extracellular volume fraction (ECV) is a marker for myocardial fibrosis and infiltration, can be quantified using cardiac computed tomography (ECVCT), and has prognostic utility in several diseases. This study aims to map out regional differences in ECVCT to obtain greater insights into the pathophysiological mechanisms of ECV expansion and its clinical implications. METHODS: Three prospective cohorts were included: patients with aortic stenosis (AS) and coexisting AS and transthyretin cardiac amyloidosis were referred for a transcatheter aortic valve replacement and had ECG-gated CT angiography and Technetium-99m-labelled 3,3-diphosphono-1,2-propanodicarboxylic acid scintigraphy to differentiate between the 2 cohorts. Controls had CT angiography and cardiac magnetic resonance demonstrating no significant coronary artery disease or infarction. Global and regional ECVCT was analyzed, and its association with mortality was assessed for patients with AS. RESULTS: In 199 patients, controls (n=65; 66% male), AS (n=115), and coexisting AS and transthyretin cardiac amyloidosis (n=19) had a global ECVCT of 26.1 (25.0-27.8%) versus 29.1 (27.5-31.1%) versus 37.4 (32.5-46.6%), respectively; P<0.001. Across cohorts, ECVCT was higher at the base (versus apex), the inferoseptum (versus anterolateral wall), and the subendocardium (versus subepicardium); P<0.05 for all. Among patients with AS, epicardial ECVCT, rather than any other regional value or global ECVCT, was the strongest predictor of mortality at a median of 3.9 (max 6.3) years (adjusted hazard ratio, 1.21 [95% CI, 1.08-1.36]; P=0.002). CONCLUSIONS: Regional differences in ECVCT suggest a predilection for fibrosis and amyloid infiltration at the base, subendocardium, inferior wall, and septum more than the anterior and lateral myocardium. ECVCT can predict long-term mortality with the subepicardium demonstrating the strongest discriminatory power. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifiers: NCT03029026 and NCT03094143.

Clinical validation of C12FDG as a marker associated with senescence and osteoarthritic phenotypes.

Chronic conditions associated with aging have proven difficult to prevent or treat. Senescence is a cell fate defined by loss of proliferative capacity and the development of a pro-inflammatory senescence-associated secretory phenotype comprised of cytokines/chemokines, proteases, and other factors that promotes age-related diseases. Specifically, an increase in senescent peripheral blood mononuclear cells (PBMCs), including T cells, is associated with conditions like frailty, rheumatoid arthritis, and bone loss. However, it is unknown if the percentage of senescent PBMCs associated with age-associated orthopedic decline could be used for potential diagnostic or prognostic use in orthopedics. Here, we report senescent cell detection using the fluorescent compound C12FDG to quantify PBMCs senescence across a large cohort of healthy and osteoarthritic patients. There is an increase in the percent of circulating C12FDG+ PBMCs that is commensurate with increases in age and senescence-related serum biomarkers. Interestingly, C12FDG+ PBMCs and T cells also were found to be elevated in patients with mild to moderate osteoarthritis, a progressive joint disease that is strongly associated with inflammation. The percent of C12FDG+ PBMCs and age-related serum biomarkers were decreased in a small subgroup of study participants taking the senolytic drug fisetin. These results demonstrate quantifiable measurements in a large group of participants that could create a composite score of healthy aging sensitive enough to detect changes following senolytic therapy and may predict age-related orthopedic decline. Detection of peripheral senescence in PBMCs and subsets using C12FDG may be clinically useful for quantifying cellular senescence and determining how and if it plays a pathological role in osteoarthritic progression.

Validation of the Openwater wearable optical system: cerebral hemodynamic monitoring during a breath-hold maneuver.

Significance: Bedside cerebral blood flow (CBF) monitoring has the potential to inform and improve care for acute neurologic diseases, but technical challenges limit the use of existing techniques in clinical practice. Aim: Here, we validate the Openwater optical system, a novel wearable headset that uses laser speckle contrast to monitor microvascular hemodynamics. Approach: We monitored 25 healthy adults with the Openwater system and concurrent transcranial Doppler (TCD) while performing a breath-hold maneuver to increase CBF. Relative blood flow (rBF) was derived from changes in speckle contrast, and relative blood volume (rBV) was derived from changes in speckle average intensity. Results: A strong correlation was observed between beat-to-beat optical rBF and TCD-measured cerebral blood flow velocity (CBFv), R=0.79; the slope of the linear fit indicates good agreement, 0.87 (95% CI: 0.83 -0.92). Beat-to-beat rBV and CBFv were also strongly correlated, R=0.72, but as expected the two variables were not proportional; changes in rBV were smaller than CBFv changes, with linear fit slope of 0.18 (95% CI: 0.17 to 0.19). Further, strong agreement was found between rBF and CBFv waveform morphology and related metrics. Conclusions: This first in vivo validation of the Openwater optical system highlights its potential as a cerebral hemodynamic monitor, but additional validation is needed in disease states.

Evaluating the Morphology of Unique Superficial Fissured Cartilage Lesions at the Femoral Head-Neck Junction in Patients with Femoroacetabular Impingement Syndrome.

Background: While an association between femoroacetabular impingement (FAI) and osteoarthritis (OA) has been reported, the mechanistic differences and transition between the 2 conditions is not fully understood. In FAI, cartilage lesions at the femoral head-neck junction can sometimes be visualized during hip arthroscopy. Purpose/Hypothesis: The purpose of this study was to describe a unique dimpled pattern of superficial fissured cartilage lesions on the femoral head-neck junction at impingement site in patients with FAI syndrome (FAIS) and to evaluate the clinical, histological, and genetic phenotype of this cartilage. We hypothesized that the cartilage lesions may indicate risk for, or predict occurrence of, OA. Study Design: Controlled laboratory study. Methods: Six hips (6 patients; mean age, 34.2 ± 12.9 years; range, 19-54 years) with dimpled or fissured cartilage were included among patients who underwent hip arthroscopy for treatment of FAIS from October 2020 through December 2021. This affected cartilage (dimple-pattern group) and normal cartilage (control group) on the femoral head-neck junction were collected from the same patients and evaluated for histological quantification by Mankin scores and expression of proteins related to cartilage degeneration (eg, matrix metalloproteinase [MMP]-1, MMP-2, MMP-3, MMP-10, and MMP-12, tissue inhibitor of metalloproteinase [TIMP]-1 and TMP-2, aggrecan neopepitope CS846, and hyaluronic acid [HA]) with the use of Milliplex Multiplex Assays. Results: All 6 hips were of the mixed FAI subtype. Preoperatively, 4 of 6 hips had Tönnis grade 1 radiographic changes, which was associated with greater femoral head chondral damage visualized intraoperatively. Mankin scores for the normal cartilage group and the dimple-pattern group were 0.67 ± 0.82 and 3.3 ± 0.82, respectively. Dimple pattern fissured cartilage showed a significant increase in Mankin score (P = .031) and a significant increase in protein expression of CS846 (P = .031) compared with normal cartilage. There were no significant differences in MMPs, TIMPs, or HA levels between the 2 groups. Conclusion: The dimple pattern fissured cartilage, compared to normal cartilage, showed histologically significant cartilage degeneration and a significant increase in protein expression of CS846, a biomarker for early OA. Clinical Relevance: This lesion serves as helpful visual indicator of early degeneration of the cartilage of femoral head-neck junction caused by FAIS.

Predictors of outcome in patients with moderate mixed aortic valve disease.

OBJECTIVES: Grading the severity of moderate mixed aortic stenosis and regurgitation (MAVD) is challenging and the disease poorly understood. Identifying markers of haemodynamic severity will improve risk stratification and potentially guide timely treatment. This study aims to identify prognostic haemodynamic markers in patients with moderate MAVD. METHODS: Moderate MAVD was defined as coexisting moderate aortic stenosis (aortic valve area (AVA) 1.0-1.5 cm2) and moderate aortic regurgitation (vena contracta (VC) 0.3-0.6 cm). Consecutive patients diagnosed between 2015 and 2019 were included from a multicentre registry. The primary composite outcome of death or heart failure hospitalisation was evaluated among these patients. Demographics, comorbidities, echocardiography and treatment data were assessed for their prognostic significance. RESULTS: 207 patients with moderate MAVD were included, aged 78 (66-84) years, 56% male sex, AVA 1.2 (1.1-1.4) cm2 and VC 0.4 (0.4-0.5) cm. Over a follow-up of 3.5 (2.5-4.7) years, the composite outcome was met in 89 patients (43%). Univariable associations with the primary outcome included older age, previous myocardial infarction, previous cerebrovascular event, atrial fibrillation, New York Heart Association >2, worse renal function, tricuspid regurgitation ≥2 and mitral regurgitation ≥2. Markers of biventricular systolic function, cardiac remodelling and transaortic valve haemodynamics demonstrated an inverse association with the primary composite outcome. In multivariable analysis, peak aortic jet velocity (Vmax) was independently and inversely associated with the composite outcome (HR: 0.63, 95% CI 0.43 to 0.93; p=0.021) in an adjusted model along with age (HR: 1.05, 95% CI 1.03 to 1.08; p<0.001), creatinine (HR: 1.002, 95% CI 1.001 to 1.003; p=0.005), previous cerebrovascular event (85% vs 42%; HR: 3.04, 95% CI 1.54 to 5.99; p=0.001) and left ventricular ejection fraction (LVEF) (HR: 0.97, 95% CI 0.95 to 0.99; p=0.007). Patients with Vmax ≤2.8 m/s and LVEF ≤50% (n=27) had the worst outcome compared with the rest of the population (72% vs 41%; HR: 3.87, 95% CI 2.20 to 6.80; p<0.001). CONCLUSIONS: Patients with truly moderate MAVD have a high incidence of death and heart failure hospitalisation (43% at 3.5 (2.5-4.7) years). Within this group, a high-risk group characterised by disproportionately low aortic Vmax (≤2.8 m/s) and adverse remodelling (LVEF ≤50%) have the worst outcomes.

Integrative and comparative genomic analyses of mammalian macrophage responses to intracellular mycobacterial pathogens.

Mycobacterium tuberculosis, the causative agent of human tuberculosis (hTB), is a close evolutionary relative of Mycobacterium bovis, which causes bovine tuberculosis (bTB), one of the most damaging infectious diseases to livestock agriculture. Previous studies have shown that the pathogenesis of bTB disease is comparable to hTB disease, and that the bovine and human alveolar macrophage (bAM and hAM, respectively) transcriptomes are extensively reprogrammed in response to infection with these intracellular mycobacterial pathogens. In this study, a multi-omics integrative approach was applied with functional genomics and GWAS data sets across the two primary hosts (Bos taurus and Homo sapiens) and both pathogens (M. bovis and M. tuberculosis). Four different experimental infection groups were used: 1) bAM infected with M. bovis, 2) bAM infected with M. tuberculosis, 3) hAM infected with M. tuberculosis, and 4) human monocyte-derived macrophages (hMDM) infected with M. tuberculosis. RNA-seq data from these experiments 24 h post-infection (24 hpi) was analysed using three computational pipelines: 1) differentially expressed genes, 2) differential gene expression interaction networks, and 3) combined pathway analysis. The results were integrated with high-resolution bovine and human GWAS data sets to detect novel quantitative trait loci (QTLs) for resistance to mycobacterial infection and resilience to disease. This revealed common and unique response macrophage pathways for both pathogens and identified 32 genes (12 bovine and 20 human) significantly enriched for SNPs associated with disease resistance, the majority of which encode key components of the NF-κB signalling pathway and that also drive formation of the granuloma.

Hospital-Level Variability in Reporting of Ischemic Stroke Subtypes and Supporting Diagnostic Evaluation in GWTG-Stroke Registry.

BACKGROUND: Secondary prevention of ischemic stroke (IS) requires adequate diagnostic evaluation to identify the likely etiologic subtype. We describe hospital-level variability in diagnostic testing and IS subtyping in a large nationwide registry. METHODS AND RESULTS: We used the GWTG-Stroke (Get With The Guidelines-Stroke) registry to identify patients hospitalized with a diagnosis of acute IS at 1906 hospitals between January 1, 2016, and September 30, 2017. We compared the documentation rates and presence of risk factors, diagnostic testing, achievement/quality measures, and outcomes between patients with and without reported IS subtype. Recording of diagnostic evaluation was optional in all IS subtypes except cryptogenic, where it was required. Of 607 563 patients with IS, etiologic IS subtype was documented in 57.4% and missing in 42.6%. Both the rate of missing stroke pathogenesis and the proportion of cryptogenic strokes were highly variable across hospitals. Patients missing stroke pathogenesis less frequently had documentation of risk factors, evidence-based interventions, or discharge to home. The reported rates of major diagnostic testing, including echocardiography, carotid and intracranial vascular imaging, and short-term cardiac monitoring were <50% in patients with documented IS pathogenesis, although these variables were missing in >40% of patients. Long-term cardiac rhythm monitoring was rarely reported, even in cryptogenic stroke. CONCLUSIONS: Reporting of IS etiologic subtype and supporting diagnostic testing was low overall, with high rates of missing optional data. Improvement in the capture of these data elements is needed to identify opportunities for quality improvement in the diagnostic evaluation and secondary prevention of stroke.

A Paradigm Shift from International to Transnational Medical Education.

In recent years, the number of medical students seeking international opportunities has grown. To satisfy these demands, collaborative international programs have been developed. However, the benefits of these programs are limited as they employ an international medical education (IME) approach where only the students are exchanged. In this commentary, we discuss the current models of IME and propose a paradigm shift to a transnational approach wherein the student, faculty, and curriculum are exchanged allowing for increased integration and awareness of cultural and educational approaches to treatment that can be retained and incorporated into future practice to advance healthcare across the globe.

Differential thrombectomy utilization across hospital classifications in the United States.

OBJECTIVES: To determine hospital-level factors associated with thrombectomy uptake. MATERIALS AND METHODS: The Nationwide Emergency Department Sample was retrospectively queried to determine the total number of thrombectomies performed based on different hospital characteristics. Joint point analysis was used to determine which years were associated with significant increases in the number of high-volume thrombectomy centers (ostensibly defined as >50 thrombectomies/year), thrombectomy-capable centers (>15 thrombectomies/year), and total number of thrombectomies performed. Multivariable logistic regression was used to determine hospital factors associated with having an increased odds of performing thrombectomies, and of being classified as a high-volume thrombectomy or a thrombectomy-capable center. RESULTS: Between 2007-2020 there was a stepwise increase in the number of thrombectomy-capable and high-volume thrombectomy centers in the United States. In 2020, there were a total of 15,705 thrombectomies performed, with 89 high-volume thrombectomy centers, and 359 thrombectomy-capable centers. The number of thrombectomy-capable centers significantly increased after 2011. After 2013 and 2016 there was a significant change in the growth rate of high-volume thrombectomy centers. There was also a significant increase in the total number of thrombectomies performed after 2016. Hospital characteristics that were associated with an increased likelihood of being classified as thrombectomy-capable or high-volume included trauma level 1 and 2 hospitals. CONCLUSIONS: Between 2007 and 2020, there was a marked growth in thrombectomy utilization for acute ischemic stroke. This growth outpaced new diagnoses of ischemic stroke, and was driven largely by certain hospital types, with the greatest rises following seminal publications of positive randomized thrombectomy trials.

A Shorter Door-In-Door-Out Time Is Associated with Improved Outcome in Large Vessel Occlusion Stroke.

Introduction: Endovascular thrombectomy (EVT) significantly improves outcomes in large vessel occlusion stroke (LVOS). When a patient with a LVOS arrives at a hospital that does not perform EVT, emergent transfer to an endovascular stroke center (ESC) is required. Our objective was to determine the association between door-in-door-out time (DIDO) and 90-day outcomes in patients undergoing EVT. Methods: We conducted an analysis of the Optimizing Prehospital Stroke Systems of Care-Reacting to Changing Paradigms (OPUS-REACH) registry of 2,400 LVOS patients treated at nine ESCs in the United States. We examined the association between DIDO times and 90-day outcomes as measured by the modified Rankin scale. Results: A total of 435 patients were included in the final analysis. The mean DIDO time for patients with good outcomes was 17 minute shorter than patients with poor outcomes (122 minutes [min] vs 139 min, P = 0.04). Absolute DIDO cutoff times of ≤60 min, ≤90 min, or ≤120 min were not associated with improved functional outcomes (46.4 vs 32.3%, P = 0.12; 38.6 vs 30.6%, P = 0.10; and 36.4 vs 28.9%, P = 0.10, respectively). This held true for patients with hyperacute strokes of less than four-hour onset. Lower baseline National Institutes of Health Stroke Scale (NIHSS) score (11.9 vs 18.2, P = <.001) and younger age (62.5 vs 74.9 years (P < .001) were associated with improved outcomes. On multiple regression analysis, age (odds ratio [OR] 1.71, 95% confidence interval [CI] 1.45-2.02) and baseline NIHSS score (OR 1.67, 95% CI 1.42-1.98) were associated with improved outcomes while DIDO time was not associated with better outcome (OR 1.13, 95% CI 0.99-1.30). Conclusion: Although the DIDO time was shorter for patients with a good outcome, this was non-significant in multiple regression analysis. Receipt of intravenous thrombolysis and time to EVT were not associated with better outcomes, while male gender, lower age, arrival by private vehicle, and lower NIHSS score portended better outcomes. No absolute DIDO-time cutoff or modifiable factor was associated with improved outcomes for LVOS. This study underscores the need to streamline DIDO times but not to set an artificial DIDO time benchmark to meet.

Delay in hospital presentation is the main reason large vessel occlusion stroke patients do not receive intravenous thrombolysi.

Objectives: Intravenous thrombolysis (IVT) and endovascular therapy (EVT) are the mainstays of treatment for large vessel occlusion stroke (LVOS). Prior studies have examined why patients have not received IVT, the most cited reasons being last-known-well (LKW) to hospital arrival of >4.5 hours and minor/resolving stroke symptoms. Given that LVOS patients typically present moderate-to-severe neurologic deficits, these patients should be easier to identify and treat than patients with minor strokes. This investigation explores why IVT was not administered to a cohort of LVOS patients who underwent EVT. Methods: This is an analysis of the Optimizing the Use of Prehospital Stroke Systems of Care (OPUS-REACH) registry, which contains patients from 9 endovascular centers who underwent EVT between 2015 and 2020. The exposure of interest was the receipt of intravenous thrombolysis. Descriptive summary statistics are presented as means and SDs for continuous variables and as frequencies with percentages for categorical variables. Two-sample t tests were used to compare continuous variables and the chi-square test was used to compare categorical variables between those who received IVT and those who did not receive EVT. Results: Two thousand forty-three patients were included and 60% did not receive IVT. The most common reason for withholding IVT was LKW to arrival of >4.5 (57.2%). The second most common contraindication was oral anticoagulation (15.5%). On multivariable analysis, 2 factors were associated with not receiving IVT: increasing age (odds ratio [OR] 0.86; 95% confidence interval [CI] 0.78-0.93) and increasing time from LKW-to hospital arrival (OR 0.45 95% CI 0.46-0.49). Conclusion: Like prior studies, the most frequent reason for exclusion from IVT was a LKW to hospital presentation of >4.5 hours; the second reason was anticoagulation. Efforts must be made to increase awareness of the time-sensitive nature of IVT and evaluate the safety of IVT in patients on oral anticoagulants.

Validation of the Openwater wearable optical system: cerebral hemodynamic monitoring during a breath hold maneuver.

Bedside cerebral blood flow (CBF) monitoring has the potential to inform and improve care for acute neurologic diseases, but technical challenges limit the use of existing techniques in clinical practice. Here we validate the Openwater optical system, a novel wearable headset that uses laser speckle contrast to monitor microvascular hemodynamics. We monitored 25 healthy adults with the Openwater system and concurrent transcranial Doppler (TCD) while performing a breath-hold maneuver to increase CBF. Relative blood flow (rBF) was derived from the changes in speckle contrast, and relative blood volume (rBV) was derived from the changes in speckle average intensity. A strong correlation was observed between beat-to-beat optical rBF and TCD-measured cerebral blood flow velocity (CBFv), R=0.79; the slope of the linear fit indicates good agreement, 0.87 (95% CI:0.83-0.92). Beat-to-beat rBV and CBFv were strongly correlated, R=0.72, but as expected the two variables were not proportional; changes in rBV were smaller than CBFv changes, with linear fit slope of 0.18 (95% CI:0.17-0.19). Further, strong agreement was found between rBF and CBFv waveform morphology and related metrics. This first in vivo validation of the Openwater optical system highlights its potential as a cerebral hemodynamic monitor, but additional validation is needed in disease states.