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Treatment of recurrent MR after initially successful MitraClip procedure can pose therapeutic challenges. We report a successful case of redo MitraClip to treat recurrent inter-clip MR due to progression of underlying degenerative valvular pathology with prolapsing posterior mitral leaflet between the two prior clips. In this vignette, we describe the novel use of quantitative coronary arteriography (QCA) to select redo MitraClip as the treatment strategy.

Background: Continued smoking after stroke is associated with a high risk of stroke recurrence and other cardiovascular disease. We sought to comprehensively understand the epidemiology of smoking cessation in stroke survivors in the United States. Furthermore, we compared smoking cessation in stroke and cancer survivors because cancer is another smoking-related condition in which smoking cessation is prioritized. Methods: We performed a cross-sectional analysis of data from the Centers for Disease Control and Prevention Behavioral Risk Factor Surveillance System, an annual, nationally representative health survey. Using pooled data from 2013 to 2019, we identified stroke and cancer survivors with a history of smoking. We used survey procedures to estimate frequencies and summarize quit ratios with attention to demographic and geographic (state-wise and rural-urban) factors for stroke survivors. The quit ratio is conventionally defined as the proportion of ever smokers who have quit. Then, we used multivariable logistic regression to compare quit ratios in stroke and cancer survivors while adjusting for demographics and smoking-related comorbidities. Results: Among 4 434 604 Americans with a history of stroke and smoking, the median age was 68 years (interquartile range, 59–76), and 45.4% were women. The overall quit ratio was 60.8% (95% CI, 60.1%–61.6%). Quit ratios varied by age group, sex, race and ethnicity, and several geographic factors. There was marked geographic variation in quit ratios, ranging from 48.3% in Kentucky to 71.5% in California. Furthermore, compared with cancer survivors, stroke survivors were less likely to have quit smoking (odds ratio, 0.72 [95% CI, 0.67–0.79]) after accounting for differences in demographics and smoking-related comorbidities. Conclusions: There were considerable demographic and geographic disparities in smoking quit ratios in stroke survivors, who were less likely to have quit smoking than cancer survivors. A targeted initiative is needed to improve smoking cessation for stroke survivors.

The aim of this study was to compare the incremental prognostic value of coronary computed tomography (CT) angiography (CCTA)-derived machine learning fractional flow reserve CT (ML-FFRct) versus that of ischemia detected on single-photon emission-computed tomography (SPECT) myocardial perfusion imaging (MPI) on incident cardiovascular outcomes.SPECT MPI and ML-FFRct are noninvasive tools that can assess the hemodynamic significance of coronary atherosclerotic disease.We studied a retrospective cohort of consecutive patients who underwent clinically indicated CCTA and SPECT MPI. ML-FFRct was computed using a ML prototype. The primary outcome was all-cause mortality and nonfatal myocardial infarction (D/MI), and the secondary outcome was D/MI and unplanned revascularization, percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG) occurring more than 90 days postimaging. Multiple nested multivariate cox regression was used to model a scenario wherein an initial anatomical assessment was followed by a functional assessment.A total of 471 patients (mean age: 64 ± 13 year; 53% males) were included. Comorbidities were prevalent (78% hypertension, 66% diabetes, 81% dyslipidemia). ML-FFRct was 0.8 in at least 1 proximal/midsegment was present in 41.6% of patients, and ischemia on MPI was present in 13.8%. After a median follow-up of 18 months, 7% of patients (n = 33) experienced D/MI. On multivariate Cox proportional analysis, the presence of ischemia on MPI but not ML-FFRct significantly predicted D/MI (HR: 2.3; 95% CI: 1.0-5.0; P = 0.047; or HR: 0.7; 95% CI: 0.3-1.4; P = 0.306 respectively) when added to CCTA obstructive stenosis. Furthermore, the model with SPECT ischemia had higher global chi-square result and significantly improved reclassification. Results were similar using the secondary outcome and on several sensitivity analyses.In a high-risk patient cohort, SPECT MPI but not ML-FFRct adds independent and incremental prognostic information to CCTA-based anatomical assessment and clinical risk factors in predicting incident outcomes.

Presence of an endoleak can compromise aneurysm exclusion after endovascular abdominal aortic aneurysm repair (EVAR). Type II endoleaks (T2Es) are most common and may cause sac expansion. We report outcomes of translumbar embolization (TLE) of T2Es following EVAR.We conducted a retrospective chart review of patients with T2E after EVAR treated with TLE from 2011 to 2018 at a single academic institution. Treatment indications were the presence of persistent T2E and aneurysm growth ≥5 mm. Sac stabilization was defined as growth ≤5 mm throughout the follow-up period.Thirty consecutive patients were identified. The majority were men (n = 24), with a mean age of 74.3 years (95% confidence interval [CI], 70.9-77.6 years). The most common comorbidities were hypertension (83.3%) and coronary artery disease (54.0%). The mean maximal sac diameter at T2E discovery was 5.8 cm (95% CI, 5.4-6.2 cm). The mean time to intervention from endoleak discovery was 33.7 ± 28 months with a mean growth of 0.84 cm (95% CI, 0.48-1.2 cm) during that time period. The mean follow-up time after TLE was 19.1 months (95% CI, 11.1-27.2 months). Twenty-eight patients were treated with cyanoacrylate glue (CyG) alone, and two were treated with CyG plus coil embolization (CE). There was immediate complete endoleak resolution as assessed intraoperatively, and sac stabilization in 15 cases (50.0%). Eleven patients (36.7%) had evidence of persistent T2E on initial imaging after the embolization procedure; additional follow-up revealed eventual sac stabilization at a mean of 21.3 ± 7.2 months, and therefore, these patients did not require further intervention. In the remaining four cases (13.3%), there was persistent T2E after the initial TLE, requiring a second intervention. Repeat TLE stabilized growth in three of these four patients after a mean of 17.6 ± 12.9 months. One patient required open sacotomy and ligation of lumbar vessels due to continued persistence of the T2E and continued aneurysm growth. There were no ischemic complications related to the embolization procedures. Factors associated with persistent endoleak after initial embolization were larger aneurysm diameter at the time of initial endoleak identification (P .001) and the use of antiplatelet agents (P .02). The use of anticoagulation was not a significant risk factor for endoleak recurrence or aneurysm growth after TLE.TLE of T2E is a safe and effective treatment option for T2E with aneurysm growth following EVAR. Patients taking antiplatelet medication and those with larger aneurysms at the time of endoleak identification appear to be at increased risk for persistent endoleak and need for subsequent procedures following initial TLE. These patients may require more intensive monitoring and follow-up.

We present the case of a patient with a recent history of ischemic stroke who presented with clicking larynx syndrome, a condition in which clicking noises in the larynx can be provoked by movement of the head and neck. Diagnostic imaging revealed unusual development and posterior angulation of the superior horn of the thyroid cartilage that potentially was causing trauma to the left common carotid artery. We deduced that symptomatic impingement of the carotid artery by the thyroid cartilage was not only the cause of the patient's clicking larynx syndrome, but also suspected to be the cause of her prior strokes due to repetitive trauma resulting in thrombus. The patient was managed surgically with thyroplasty and transcervical resection of the left greater cornu of the thyroid cartilage with resolution of her symptoms. Anatomical displacement of the thyroid cartilage can manifest as clicking larynx syndrome as well as cause mechanical injury to the carotid artery, resulting in turbulent flow, possible thrombosis, and stroke. Laryngoscope, 2021.

The availability of electronic health record (EHR)-linked biobank data for research presents opportunities to better understand complex ocular diseases. Developing accurate computable phenotypes for ocular diseases for which gold standard diagnosis includes imaging remains inaccessible in most biobank-linked EHRs. The objective of this study was to develop and validate a computable phenotype to identify primary open-angle glaucoma (POAG) through accessing the Department of Veterans Affairs (VA) Computerized Patient Record System (CPRS) and Million Veteran Program (MVP) biobank. Accessing CPRS clinical ophthalmology data from VA Medical Center Eye Clinic (VAMCEC) patients, we developed and iteratively refined POAG case and control algorithms based on clinical, prescription, and structured diagnosis data (ICD-CM codes). Refinement was performed via detailed chart review, initially at a single VAMCEC (n = 200) and validated at two additional VAMCECs (n = 100 each). Positive and negative predictive values (PPV, NPV) were computed as the proportion of CPRS patients correctly classified with POAG or without POAG, respectively, by the algorithms, validated by ophthalmologists and optometrists with access to gold-standard clinical diagnosis data. The final algorithms performed better than previously reported approaches in assuring the accuracy and reproducibility of POAG classification (PPV >83% and NPV >97%) with consistent performance in Black or African American and in White Veterans. Applied to the MVP to identify cases and controls, genetic analysis of a known POAG-associated locus further validated the algorithms. We conclude that ours is a viable approach to use combined EHR-genetic data to study patients with complex diseases that require imaging confirmation.

Background: No study has specifically evaluated how ulnar neuritis and ulnar nerve transposition affect outcomes in baseball players undergoing ulnar collateral ligament (UCL) reconstruction (UCLR). Purpose: To evaluate the effects of ulnar neuritis and ulnar nerve transposition in baseball pitchers undergoing UCLR in regard to return to sport, time to return to sport, and need for revision or additional surgery. Study Design: Cohort study; Level of evidence, 3. Methods: At a single institution, all consecutive baseball pitchers undergoing UCLR between 2002 and 2015 were identified. Ulnar neuritis was diagnosed preoperatively by the following criteria: ulnar nerve symptoms, Tinel sign at the elbow, symptomatic subluxation, and numbness/paresthesia in an ulnar nerve distribution of the hand. The primary outcome of the study was return to sport. The secondary outcomes of the study were time to return to sport, length of playing career, and revision or additional surgery. Results: A total of 578 UCLRs were performed in baseball players; of these, 500 UCLRs were performed in pitchers. Ulnar neuritis was diagnosed in 97 (19.4%) baseball pitchers presenting with UCL injury. There were no significant differences in patient characteristics or surgical techniques performed for reconstruction between baseball pitchers with and without ulnar neuritis. In review of injury characteristics, ulnar neuritis was significantly more likely to be diagnosed in pitchers with an acute onset of UCL injury ( P = .03). Transposition of the ulnar nerve was more commonly performed in players with ulnar neuritis (47%) versus those without ulnar neuritis (10%; P = .0001). The players who had ulnar neuritis and underwent UCLR had a significantly lower odds of returning to sport (odds ratio, 0.45; P = .04); however, no significant difference was found for time to return to sport and length of playing career for those with and without ulnar neuritis ( P = .38 and .51, respectively). Conclusion: The study suggests that ulnar neuritis, when present preoperatively in baseball pitchers undergoing UCLR, may adversely affect their ability to return to sport, whereas ulnar nerve transposition at the time of UCLR does not alter the ability to return to sport.

Purpose of review Nonalcoholic fatty liver disease (NAFLD) is a common comorbidity and has wide ranging extrahepatic manifestations, including through cardiometabolic pathways. As such, there is growing interest in the impact of NAFLD on cerebrovascular disease and brain health more broadly. In this review, we assess recent research into understanding the association between NAFLD and brain health while highlighting potential clinical implications. Recent findings Mechanistically, NAFLD is characterized by both a proinflammatory and proatherogenic state, which results in vascular inflammation and neurodegeneration, potentially leading to clinical and subclinical cerebrovascular disease. Mounting epidemiological evidence suggests an association between NAFLD and an increased risk and severity of stroke, independent of other vascular risk factors. Studies also implicate NAFLD in subclinical cerebrovascular disease, such as carotid atherosclerosis and microvascular disease. In contrast, there does not appear to be an independent association between NAFLD and cognitive impairment. Summary The current literature supports the formulation of NAFLD as a multisystem disease that may also have implications for cerebrovascular disease and brain health. Further prospective studies are needed to better assess a temporal relationship between the two diseases, confirm these early findings, and decipher mechanistic links.

Background Sex differences in stroke outcomes have been noted, but whether this extends to stroke recurrence is unclear. We examined sex differences in recurrent stroke using data from the Platelet-Oriented Inhibition in New TIA and Minor Ischemic Stroke (POINT) trial. Patients and methods We assessed the risk of recurrent stroke in women compared to men using data from the POINT trial. Adults >18 years old were randomized within 12 hours of onset of minor ischemic stroke or transient ischemic attack (TIA), and followed for up to 90 days for ischemic stroke, our primary outcome. We used Cox proportional hazards model adjusted for demographics and stroke risk factors to evaluate the association between sex and stroke recurrence. We used interaction term testing and prespecified subgroup analyses to determine if the association between sex and recurrent stroke differed by age (60 years old), locale (US versus non-US), and index event type (stroke versus TIA). Last, we evaluated whether sex modified the effect of common stroke risk factors on stroke recurrence. Results Of 4,881 POINT trial participants with minor stroke or high-risk TIA, 2,195 (45%) were women. During the 90-day follow-up period, 267 ischemic strokes occurred; 121 were in women and 146 in men. The cumulative risk of recurrent ischemic stroke was not significantly different among women (5.76%; 95% CI, 4.84%–6.85%) compared to men (5.67%; 95% CI, 4.83%–6.63%). Women were not at a different risk of recurrent ischemic stroke compared to men (hazard ratio [HR], 1.02; 95% CI, 0.80–1.30) in unadjusted models or after adjusting for covariates. However, there was a significant interaction of age with sex (P=0.04). Among patients Discussion and Conclusion Among patients with minor stroke or TIA, the risk of recurrent ischemic stroke and the impact of common stroke risk factors did not differ between men and women.

With the exponential increase in the use of endovascular techniques in the treatment of peripheral artery disease, our understanding of factors that affect intervention failures continues to grow. We sought to assess the outcomes of percutaneous transluminal angioplasty for isolated de novo superficial femoral artery (SFA) disease based on balloon diameter.The Vascular Quality Initiative database was queried for patients undergoing percutaneous balloon angioplasty for isolated de novo atherosclerotic SFA disease. Based on the diameter of the angioplasty balloon as a surrogate measure of arterial diameter, patients were stratified into 2 groups: group 1, balloon diameter5 mm (354 patients) and group 2, balloon diameter ≥5 mm (1,550 patients). The primary patency and major adverse limb event (MALE) were estimated by the Kaplan-Meier method and compared with the log-rank test, based on vessel diameter. Multivariable Cox regression analysis was used to determine factors associated with the primary patency.From January 2010 through December 2018, a total of 1,904 patients met criteria for analysis, with a mean follow-up of 13.3 ± 4.5 months. The mean balloon diameters were 3.92 ± 0.26 mm and 5.47 ± 0.55 mm in group 1 and 2, respectively (P0.001). The mean length of treatment and distribution of TASC lesions were not statistically different between the groups. Primary patency at 18 months was significantly lower in group 1, compared with group 2 (55% vs. 67%; log-rank P0.001). The MALE rate was higher in group 1 than group 2 (33% vs. 26%; log-rank P0.001). Among patients with claudication, there was no significant difference in the primary patency (61% vs 68%; log-rank P = 0.073) and MALE (27% vs. 22%; log-rank P = 0.176) at 18 months between groups 1 and 2, respectively. However, in patients with CLTI, group 1 had significantly lower 18-month primary patency (47% vs. 64%; log-rank P0.014) and higher MALE rates (41% vs. 35%; log-rank P = 0.012) than group 2. Cox proportional hazard analysis confirmed that balloon diameter5 mm was independently associated with increased risks of primary patency loss (HR 1.35; 95% CI, 1.04-1.72; P = 0.021) and MALE (HR 1.29; 95% CI, 1-1.67; P = 0.048) at 18-months.In patients undergoing isolated SFA balloon angioplasty for CLTI, smaller SFA (5 mm) was associated with worse primary patency and MALE. Using balloon size as a surrogate, our findings suggest that patients with a smaller SFA diameter appear to be at increased risk for treatment failure and warrant closer surveillance. Furthermore, these patients may also be considered for alternative approaches, including open revascularization.

Adjunctive false lumen embolization (FLE) with thoracic endovascular aortic repair (TEVAR) in patients with chronic aortic dissection is thought to induce FL thrombosis and favorable aortic remodeling. However, these data are derived from small single-institution experiences and the potential benefit of FLE remains unproven. In this study, we examined perioperative and midterm outcomes of patients with aortic dissection undergoing concomitant TEVAR and FLE.* METHODS: : Patients 18 or older who underwent TEVAR for chronic aortic dissection with known FLE status in the Society for Vascular Surgery Vascular Quality Initiative database between January 2010 and February 2020 were included. Ruptured patients and emergent procedures were excluded. Patient characteristics, operative details and outcomes were analyzed by group: TEVAR with or without FLE. Primary outcomes were in-hospital post-operative complications and all-cause mortality. Secondary outcomes included follow-up mean maximum aortic diameter change, rates of false lumen thrombosis, re-intervention rates, and mortality.884 patients were included: 46 had TEVAR/FLE and 838 had TEVAR alone. There was no significant difference between groups in terms of age, gender, comorbidities, prior aortic interventions, mean maximum pre-operative aortic diameter (5.1cm vs. 5.0cm, P=0.43), presentation symptomatology, or intervention indication. FLE was associated with significantly longer procedural times (178min vs. 146min, P=0.0002), increased contrast use (134mL vs. 113mL, P=0.02), and prolonged fluoroscopy time (34min vs. 21min, P0.0001). However, FLE was not associated with a significant difference in post-operative complications (17.4% vs. 13.8%, P=0.51), length of stay (6.5 vs. 5.7 days, P=0.18), or in-hospital all-cause mortality (0% vs. 1.3%, P=1). In mid-term follow-up (median 15.5months, IQR 2.2-36.2 months), all-cause mortality trended lower, but was not significant (2.2% vs. 7.8%); and Kaplan-Meier analysis demonstrated no difference in overall survival between groups (P=0.23). By Cox regression analysis, post-operative complications had the strongest independent association with all-cause mortality (HR 2.65, 95% CI 1.56-4.5, P0.001). In patients with available follow-up imaging and re-intervention status, mean aortic diameter change (n=337, -0.71cm vs. -0.69cm, P=0.64) and re-intervention rates (n=487, 10% vs. 11.4%, P=1) were similar.Adjunctive FLE, despite increased procedural times, can be performed safely for patients with chronic dissection without significantly higher overall perioperative morbidity or mortality. TEVAR/FLE demonstrates trends for improved survival and increased rates of FL thrombosis in the treated thoracic segment; however, given the lack of evidence to suggest a significant reduction in re-intervention rates or induction of more favorable aortic remodeling compared to TEVAR alone, the overall utility of this technique in practice remains unclear. Further investigation is needed to determine the most appropriate role for FLE in managing chronic aortic dissections.

Although cell-free DNA (cfDNA) tests have emerged as a potential non-invasive alternative to bone marrow biopsies for monitoring clonal hematopoiesis in hematologic diseases, whether commercial cfDNA assays can be implemented for the detection and quantification of de novo clonal hematopoiesis in place of blood cells is uncertain. In this study, peripheral plasma cfDNA samples available from patients with aplastic anemia (n=25) or myelodysplastic syndromes (n=27) and a healthy cohort (n=107) were screened for somatic variants in genes related to hematologic malignancies using a Clinical Laboratory Improvement Amendments-certified panel. Results were further compared to DNA sequencing of matched blood cells. In reported results, 85% of healthy subjects, 36% of patients with aplastic anemia and 74% of patients with myelodysplastic syndromes were found to have somatic cfDNA variants, most frequently in DNMT3A, TET2, ASXL1 and SF3B1. However, concordance between cfDNA and blood cell findings was poor for the detection of clonal hematopoiesis when the allele frequency of the variants was

Summary An important goal of clinical genomics is to be able to estimate the risk of adverse disease outcomes. Between 5% and 10% of individuals with ulcerative colitis (UC) require colectomy within 5 years of diagnosis, but polygenic risk scores (PRSs) utilizing findings from genome-wide association studies (GWASs) are unable to provide meaningful prediction of this adverse status. By contrast, in Crohn disease, gene expression profiling of GWAS-significant genes does provide some stratification of risk of progression to complicated disease in the form of a transcriptional risk score (TRS). Here, we demonstrate that a measured TRS based on bulk rectal gene expression in the PROTECT inception cohort study has a positive predictive value approaching 50% for colectomy. Single-cell profiling demonstrates that the genes are active in multiple diverse cell types from both the epithelial and immune compartments. Expression quantitative trait locus (QTL) analysis identifies genes with differential effects at baseline and week 52 follow-up, but for the most part, differential expression associated with colectomy risk is independent of local genetic regulation. Nevertheless, a predicted polygenic transcriptional risk score (PPTRS) derived by summation of transcriptome-wide association study (TWAS) effects identifies UC-affected individuals at 5-fold elevated risk of colectomy with data from the UK Biobank population cohort studies, independently replicated in an NIDDK-IBDGC dataset. Prediction of gene expression from relatively small transcriptome datasets can thus be used in conjunction with TWASs for stratification of risk of disease complications.

Objectives The aim of this study was to evaluate clinical characteristics, mechanisms of failure, and outcomes of transcatheter aortic valve replacement (TAVR) explantation. Background Surgical explantation following TAVR may be required for structural valve degeneration, paravalvular leak, infection, or other reasons. However, in-depth data on indications and outcomes are lacking. Methods Data from a multicenter, international registry (EXPLANT-TAVR) of patients who underwent TAVR explantation were reviewed retrospectively. Explantations performed during the same admission as initial TAVR were excluded. Clinical and echocardiographic outcomes were evaluated. Median follow-up duration was 6.7 months (interquartile range [IQR]: 1.0-18.8 months) after TAVR explantation and was 97.7% complete at 30 days and 86.1% complete at 1 year. Results From November 2009 to September 2020, 269 patients across 42 centers with a mean age of 72.7 ± 10.4 years underwent TAVR explantation. About one quarter (25.9%) were deemed low surgical risk at index TAVR, and median Society of Thoracic Surgeons risk at TAVR explantation was 5.6% (IQR: 3.2%-9.6%). The median time to explantation was 11.5 months (IQR: 4.0-32.4 months). Balloon-expandable and self-expanding or mechanically expandable valves accounted for 50.9% and 49.1%, respectively. Indications for explantation included endocarditis (43.1%), structural valve degeneration (20.1%), paravalvular leak (18.2%), and prosthesis-patient mismatch (10.8%). Redo TAVR was not feasible because of unfavorable anatomy in 26.8% of patients. Urgent or emergency cases were performed in 53.1% of patients, aortic root replacement in 13.4%, and 54.6% had concomitant cardiac procedures. Overall survival at last follow-up was 76.1%. In-hospital, 30-day, and 1-year mortality rates were 11.9%, 13.1%, and 28.5%, respectively, and stroke rates were 5.9%, 8.6%, and 18.7%, respectively. Conclusions The EXPLANT-TAVR registry reveals that surgical risks associated with TAVR explantation are not negligible and should be taken into consideration in the lifetime management of aortic stenosis.

Objectives The aim of this study was to determine clinical and echocardiographic characteristics, mechanisms of failure, and outcomes of mitral valve (MV) surgery after transcatheter edge-to-edge repair (TEER). Background Although >100,000 mitral TEER procedures have been performed worldwide, longitudinal data on MV surgery after TEER are lacking. Methods Data from the multicenter, international CUTTING-EDGE registry were retrospectively analyzed. Clinical and echocardiographic outcomes were evaluated. Median follow-up duration was 9.0 months (interquartile range [IQR]: 1.2-25.7 months) after MV surgery, and follow-up was 96.1% complete at 30 days and 81.1% complete at 1 year. Results From July 2009 to July 2020, 332 patients across 34 centers underwent MV surgery after TEER. The mean age was 73.8 ± 10.1 years, median Society of Thoracic Surgeons risk for MV repair at initial TEER was 4.0 (IQR: 2.3-7.3), and primary/mixed and secondary mitral regurgitation were present in 59.0% and 38.5%, respectively. The median interval from TEER to surgery was 3.5 months (IQR: 0.5-11.9 months), with overall median Society of Thoracic Surgeons risk of 4.8% for MV replacement (IQR: 2.8%-8.4%). The primary indication for surgery was recurrent mitral regurgitation (33.5%), and MV replacement and concomitant tricuspid surgery were performed in 92.5% and 42.2% of patients, respectively. The 30-day and 1-year mortality rates were 16.6% and 31.3%, respectively. On Kaplan-Meier analysis, the actuarial estimates of mortality were 24.1% at 1 year and 31.7% at 3 years after MV surgery. Conclusions In this first report of the CUTTING-EDGE registry, the mortality and morbidity risks of MV surgery after TEER were not negligible, and only

Objective Somatic mutations in UBA1 cause a newly defined syndrome known as VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic syndrome). More than 50% of patients currently identified as having VEXAS met diagnostic criteria for relapsing polychondritis (RP), but clinical features that characterize VEXAS within a cohort of patients with RP have not been defined. We undertook this study to define the prevalence of somatic mutations in UBA1 in patients with RP and to create an algorithm to identify patients with genetically confirmed VEXAS among those with RP. Methods Exome and targeted sequencing of UBA1 was performed in a prospective observational cohort of patients with RP. Clinical and immunologic characteristics of patients with RP were compared based on the presence or absence of UBA1 mutations. The random forest method was used to derive a clinical algorithm to identify patients with UBA1 mutations. Results Seven of 92 patients with RP (7.6%) had UBA1 mutations (referred to here as VEXAS-RP). Patients with VEXAS-RP were all male, were on average ≥45 years of age at disease onset, and commonly had fever, ear chondritis, skin involvement, deep vein thrombosis, and pulmonary infiltrates. No patient with VEXAS-RP had chondritis of the airways or costochondritis. Mortality was greater in VEXAS-RP than in RP (23% versus 4%; P = 0.029). Elevated acute-phase reactants and hematologic abnormalities (e.g., macrocytic anemia, thrombocytopenia, lymphopenia, multiple myeloma, myelodysplastic syndrome) were prevalent in VEXAS-RP. A decision tree algorithm based on male sex, a mean corpuscular volume >100 fl, and a platelet count

Somatic mutations in UBA1 involving hematopoietic stem and myeloid cells have been reported in patients with the newly defined VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome. Here, we report clinical hematologic manifestations and unique bone marrow (BM) features in 16 patients with VEXAS. All patients were male and had a history of severe autoinflammatory and rheumatologic manifestations and a somatic UBA1 mutation (p.Met41). Ten patients had hematologic disorders: myelodysplastic syndrome (MDS; 6 of 16), multiple myeloma (2 of 16), monoclonal gammopathy of undetermined significance (2 of 16), and monoclonal B-cell lymphocytosis (2 of 16), and a few of those patients had 2 co-existing clonal processes. Although macrocytic anemia (100%) and lymphopenia (80%) were prevalent in all patients with VEXAS, thrombocytopenia and neutropenia were more common in patients with progression to MDS. All BMs in VEXAS patients had prominent cytoplasmic vacuoles in myeloid and erythroid precursors. In addition, most BMs were hypercellular with myeloid hyperplasia, erythroid hypoplasia, and varying degrees of dysplasia. All patients diagnosed with MDS were lower risk (low blast count, very good to intermediate cytogenetics) according to standard prognostic scoring with no known progression to leukemia. In addition, 10 of 16 patients had thrombotic events, including venous thromboembolism and arterial stroke. Although VEXAS presents symptomatically as a rheumatologic disease, morbidity and mortality are associated with progression to hematologic disease. Given the increased risk of developing MDS and multiple myeloma, surveillance for disease progression is important.

While fecal calprotectin (FC) is used to assess disease activity in ulcerative colitis (UC) there are little data concerning the role of serial FC levels at diagnosis in predicting clinical course. We sought to determine whether FC at diagnosis or early change following therapy predicts clinical outcomes in pediatric UC.Methods: Children with newly diagnosed UC were treated with standardized regimens of mesalamine or corticosteroids (CS). CS tapering and escalation to additional therapy or colectomy were by protocol. Patients with baseline or week 4 or week 12 FC levels were included in the analysis. Our primary outcome was CS-free remission on mesalamine at week 52. We compared the prognostic value of a baseline FC as well as a change in FC by week 4 or week 12 in predicting clinical outcomes.The study included 352 children (113 initial mesalamine, 239 initial CS, mean age 12.6 years) with UC. At Week 52, 135 (38.3%), 84 (23.8%), and 19 (5.4%) children achieved CS-free remission, needed anti-tumor necrosis factor therapy or had colectomy respectively. Baseline FC was not associated with CS-free remission at week 52. However, both week 4 (odds ratio [OR] 0.95, 95% confidence interval [CI] 0.901.00) and week 12 FC levels (OR 0.91, 95% CI 0.87-0.96) were associated with outcomes, with the latter having a stronger association with CS-free remission. Patients with a75% decrease by 12 weeks, had a 3-fold increased likelihood of CS-free remission at 1 year.Longitudinal changes in FC may predict 1 year outcomes better than values at diagnosis in children with a new diagnosis of UC.

Background Autologous vein is considered the preferred conduit for lower extremity bypass. There is, however, limited literature regarding conduit choice for open popliteal artery aneurysm (PAA) repair. We sought to compare outcomes of PAA repair using vein versus prosthetic conduits. Methods The Vascular Quality Initiative database (2003–2019) was queried for patients with PAAs undergoing elective conventional revascularization originating from the superficial femoral and popliteal arteries. Conduits were categorized as vein or prosthetic. Primary outcomes were primary graft patency, freedom from major adverse limb event (MALE) and MALE-free survival at 2-years. Kaplan-Meier method with log-rank tests was used for estimation and comparison of patency. Results A total of 1,146 limbs in 1,065 patients underwent elective open revascularization for PAA. Vein was used in 921 limbs (80%), and prosthetic in 225 (20%). Patients in the prosthetic cohort had a shorter procedure time, were older, and had a higher prevalence of COPD. Postoperatively, prosthetic patients were more likely to be started and maintained on anticoagulation without increased incidence of hematoma. There was no significant difference in the rate of surgical site infection (2% vs. 2%; P = 0.946). There was an increased tendency toward more symptomatic patients in the vein cohort although not statistically significant (49% vein vs. 41% prosthetic; P = 0.096). On a mean follow-up of 13 ± 5 months, the incidence of MALE and MALE-free survival were comparable between the two groups. The 2-year primary and secondary patency rates were similar, 87% and 96% in the vein, and 91% and 95% in the prosthetic groups, respectively. At multivariable analysis, outflow bypass targets to the infrapopliteal arteries (HR 2.05; 95% confidence interval (CI), 1.16–3.65; P = 0.014) and symptomatic aneurysm (HR 1.81; 95% CI, 1.04–3.15; P = 0.037) were independently associated with loss of primary patency. Conduit type did not make a difference in MALE-free survival, or primary graft patency at 2-years. Conclusion Our study demonstrates that conventional open PAA repair with prosthetic conduit yields results comparable to those with vein conduit with regard to primary and secondary patency and MALEs at 2-years for targets to the popliteal artery. However, when the distal target was infrapopliteal, worse outcomes were observed with prosthetic conduit. Our results suggest that vein conduit should be preferentially used for infrapopliteal targets, while prosthetic conduit confers comparable outcomes in a subset of patients who do not have suitable autologous vein conduits.

Objective To identify opportunities for discontinuing elective and nonemergency surgical cases in a regional surgical practice in response to coronavirus disease 2019 (COVID-19). Patients and Methods COVID-19 began to affect surgical practices across the United States in March 2020. On March 17, 2020, all elective and nonemergency surgical care was deferred to prepare the Mayo Clinic Health System sites in northwestern Wisconsin for an anticipated surge in patients with COVID-19. When the decision was made to reactivate the surgical practice, several major structural and operational changes were made to the regional surgical practice to optimize efficiencies. Results The structural and operational changes implemented during reactivation resulted in improved utilization of surgical resources including improvement in operating room (OR) block utilization, increased available OR time, and increased case volumes. Conclusion Surgical and procedural leaders should consider a limited-time deferral of elective surgical cases to implement widespread OR efficiency strategies. The time selected for deferral of surgical cases should target a period of historically low surgical volume to minimize disruption to patient care and impact on overall OR functions.

Thin epoxy overlays are used for improving the condition and extending the service life of bridge decks. The tensile bond pull-off strength, evaluated as per ASTM C1583, is used as the performance indicator. A failure in the substrate with a tensile strength of 250 pounds per square inch (psi) or greater is considered acceptable. However, the performance of in-service bridge decks when evaluated shows inconsistent results. Such studies failed to record and correlate the parameters that influence overlay performance during testing to clarify the observed variations. Laboratory studies by several researchers have documented a distinct performance difference when the overlays are exposed to room temperatures in comparison with elevated temperatures. However, the most influential parameters, such as the variation of substrate moisture against temperature and epoxy softening under elevated temperatures, were not measured and correlated to the observed performance. This study was initiated to provide clarification of the observed performance differences by evaluating the impact of concrete age at the time of epoxy application, concrete mix ingredients, exposure conditions, concrete microstructure development, and substrate moisture and temperature on the performance of two epoxy overlays. Experimental results confirm that (i) the performance of epoxy overlays improves when the concrete mix contains slag and (ii) substrate moisture vapor pressure and epoxy softening under elevated temperature negatively affect the overlay performance.

The International Study of Comparative Health Effectiveness with Medical and Invasive Approaches (ISCHEMIA) trial showed no difference in outcomes between medical therapy vs coronary revascularization in the management of patients with stable coronary artery disease. We aimed to determine the percentage of patients with at least moderate ischemia that would have been eligible for enrollment and evaluate the outcomes of those who would not. Consecutive patients who underwent cardiac single-photon emission computed tomography (SPECT) between April 2016 and September 2019 were identified and all-cause mortality was determined. There were a total of 1508 patients (mean age 67 ± 11.6 years, 69.5% males) with any perfusion defect on SPECT. Patients had a high prevalence of cardiac risk factors (73.4% with hypertension and 54.4% with diabetes mellitus.) Nearly half (709, 47%) had moderate-to-severe ischemia but over two-thirds (479/709, 66.3%) had at least one ISCHEMIA trial exclusion criteria. Patients meeting ISCHEMIA enrollment criteria had a significantly lower all-cause mortality than those who would have been excluded (3.91% vs. 11.3%, respectively, P

Background The Vein of Marshall Ethanol for Untreated Persistent AF (VENUS) trial demonstrated that adding vein of Marshall (VOM) ethanol infusion to catheter ablation (CA) improves ablation outcomes in persistent atrial fibrillation (AF). There was significant heterogeneity in the impact of VOM ethanol infusion on rhythm control. Objective The purpose of this study was to assess the association between outcomes and (1) achievement of bidirectional perimitral conduction block and (2) procedural volume. Methods The VENUS trial randomized patients with persistent AF (N = 343) to CA combined with VOM ethanol or CA alone. The primary outcome (freedom from AF or atrial tachycardia [AT] lasting longer than 30 seconds after a single procedure) was analyzed by 2 categories: (1) successful vs no perimitral block and (2) high- (>20 patients enrolled) vs low-volume centers. Results In patients with perimitral block, the primary outcome was reached 54.3% after VOM-CA and 37% after CA alone (P = .01). Among patients without perimitral block, freedom from AF/AT was 34.0% after VOM-CA and 37.0% after CA (P = .583). In high-volume centers, the primary outcome was reached in 56.4% after VOM-CA and 40.2% after CA (P = .01). In low-volume centers, freedom from AF/AT was 30.77% after VOM-CA and 32.61% after CA (P = .84). In patients with successful perimitral block from high-volume centers, the primary outcome was reached in 59% after VOM-CA and 39.1% after CA (P = .01). Tests for interaction were significant (P = .002 for perimitral block and P = .04 for center volume). Conclusion Adding VOM ethanol infusion to CA has a greater impact on outcomes when associated with perimitral block and performed in high-volume centers. Perimitral block should be part of the VOM procedure.

The incidence of late presentation of myocardial infarction varies between 8.5% and 40%. Late revascularization of an infarct-related artery may limit infarct size and remodeling, reduce electrical instability, and may provide supplemental blood supply to that area via collaterals. Randomized clinical trials have shown a benefit of revascularization in symptomatic and hemodynamically unstable latecomers. Image stress testing can be beneficial to guide management of asymptomatic late presenters. Higher rates of myocardial infarction complications occur with late presentations, so a high level of suspicion is required for early diagnosis. Surgical repair remains the gold standard for management of mechanical complications.

ObjectiveTo estimate the incidence of hospitalization for reversible cerebral vasoconstriction syndrome (RCVS), we identified RCVS-related hospital admissions across 11 US states in 2016.MethodsWe tested the validity of ICD-10 code I67.841 in 79 patients with hospital admissions for RCVS or other cerebrovascular diseases at 1 academic and 1 community hospital. After determining that this code had a sensitivity of 100% (95% confidence interval [CI], 82%–100%) and a specificity of 90% (95% CI, 79%–96%), we applied it to administrative data from the Healthcare Cost and Utilization Project on all hospital admissions across 11 states. Age- and sex-standardized RCVS incidence was calculated using census data. Descriptive statistics were used to analyze associated diagnoses.ResultsAcross 5,067,250 hospital admissions in our administrative data, we identified 222 patients with a discharge diagnosis of RCVS in 2016. The estimated annual age- and sex-standardized incidence of RCVS hospitalization was 2.7 (95% CI, 2.4–3.1) cases per million adults. Many patients had concomitant neurologic diagnoses, including subarachnoid hemorrhage (37%), ischemic stroke (16%), and intracerebral hemorrhage (10%). In the 90 days before the index admission, 97 patients had an emergency department (ED) visit and 34 patients a hospital admission, most commonly for neurologic, psychiatric, and pregnancy-related diagnoses. Following discharge from the RCVS hospital admission, 58 patients had an ED visit and 31 had a hospital admission, most commonly for neurologic diagnoses.ConclusionsUsing population-wide data, we estimated the age- and sex-standardized incidence of hospitalization for RCVS in US adults as approximately 3 per million per year.

Pretreatment blood counts, particularly an absolute reticulocyte count ≥25×109/L, correlate with response to immunosuppressive therapy in severe aplastic anemia. In recent trials, eltrombopag combined with standard immunosuppressive therapy yielded superior responses than those to immunosuppressive therapy alone. Our single institution retrospective study aimed to elucidate whether historical predictors of response to immunosuppressive therapy alone were also associated with response to immunosuppressive therapy plus eltrombopag. We sought correlations of blood counts, thrombopoietin levels and the presence of paroxysmal nocturnal hemoglobinuria clones with both overall and complete responses in 416 patients with severe aplastic anemia, aged 2-82 years (median, 30 years), initially treated with immunosuppressive therapy plus eltrombopag between 2012 and 2019 (n=176) or with immunosuppressive therapy alone between 1999 and 2010 (n=240). Compared to non-responders, patients in the group of overall responders to immunosuppressive therapy plus eltrombopag had significantly higher pretreatment absolute reticulocyte counts, higher neutrophil counts and reduced thrombopoietin levels, as also observed for the group treated with immunosuppressive therapy alone. Addition of eltrombopag markedly improved the overall response in subjects with an absolute reticulocyte count between 10-30×109/L from 60% (54 of 90) to 91% (62 of 68). Absolute lymphocyte count correlated with complete response in the groups treated with immunosuppressive therapy with or without eltrombopag, especially in adolescents aged ≥10 years and adults, but the correlation was reversed in younger children. Platelet count and the presence of a paroxysmal nocturnal hemoglobinuria clone did not correlate with responses to immunosuppressive therapy. Blood counts remain the best predictors of response to nontransplant therapies in severe aplastic anemia. Addition of eltrombopag to immunosuppressive therapy shifted patients with a lower absolute reticulocyte count into a better prognostic category.

Background Develop a clinical and biological predictive model for colectomy risk in children newly diagnosed with ulcerative colitis (UC). Methods This was a multicenter inception cohort study of children (ages 4-17 years) newly diagnosed with UC treated with standardized initial regimens of mesalamine or corticosteroids (CS) depending upon initial disease severity. Therapy escalation to immunomodulators or infliximab was based on predetermined criteria. Patients were phenotyped by clinical activity per the Pediatric Ulcerative Colitis Activity Index (PUCAI), disease extent, endoscopic/histologic severity, and laboratory markers. In addition, RNA sequencing defined pretreatment rectal gene expression and high density DNA genotyping by the Affymetrix UK Biobank Axiom Array. Coprimary outcomes were colectomy over 3 years and time to colectomy. Generalized linear models, Cox proportional hazards multivariate regression modeling, and Kaplan-Meier plots were used. Results Four hundred twenty-eight patients (mean age 13 years) started initial theapy with mesalamine (n = 136), oral CS (n = 144), or intravenous CS (n = 148). Twenty-five (6%) underwent colectomy at ≤1 year, 33 (9%) at ≤2 years, and 35 (13%) at ≤3 years. Further, 32/35 patients who had colectomy failed infliximab. An initial PUCAI ≥ 65 was highly associated with colectomy (P = 0.0001). A logistic regression model predicting colectomy using the PUCAI, hemoglobin, and erythrocyte sedimentation rate had a receiver operating characteristic area under the curve of 0.78 (95% confidence interval [0.73, 0.84]). Addition of a pretreatment rectal gene expression panel reflecting activation of the innate immune system and response to external stimuli and bacteria to the clinical model improved the receiver operating characteristic area under the curve to 0.87 (95% confidence interval [0.82, 0.91]). Conclusions A small group of children newly diagnosed with severe UC still require colectomy despite current therapies. Our gene signature observations suggest additional targets for management of those patients not responding to current medical therapies.

Chronic limb-threatening ischemia (CLTI) in patients with end-stage renal disease (ESRD) confers a significant survival disadvantage and is associated with a high major amputation rate. Moreover, diabetes mellitus (DM) is an independent risk factor for developing CLTI. However, the interplay between end-stage renal disease (ESRD) and DM on outcomes after peripheral revascularization for CLTI is not well established. Our goal was to assess the effect of DM on outcomes after an infrainguinal bypass for CLTI in patients with ESRD.Using the Vascular Quality Initiative dataset from January 2003 to March 2020, records for all primary infrainguinal bypasses for CLTI in patients with ESRD were included for analysis. One-year and perioperative outcomes of all-cause mortality, reintervention, amputation-free survival (AFS), and major adverse limb event (MALE) were compared for patients with DM versus those without DM.Of a total of 1,058 patients (66% male) with ESRD, 726 (69%) patients had DM, and 332 patients did not have DM. The DM group was younger (median age, 65 years vs. 68 years; P = 0.002), with higher proportions of obesity (body-mass index30 kg/m2; 34% vs. 19%; P 0.001) and current smokers (26% vs. 19%; P = 0.013). The DM group presented more frequently with tissue loss (76% vs. 66%; P 0.001). A distal bypass anastomosis to tibial vessels was more frequently performed in the DM group compared to the non-DM group (57% vs. 45%; P 0.001). DM was independently associated with higher perioperative MALE (OR 1.34; 95% CI, 1.06-1.68; P = 0.013), without increased risks of loss of primary patency and composite outcomes of amputation or death. On the mean follow-up of 11.4 ± 5.5 months, DM patients had a significantly higher rate of one-year MALEs (43% vs. 32%; P = 0.001). However, the one-year primary patency and AFS did not differ significantly. After adjusting for confounders, the risk-adjusted hazards for MALE (HR 1.34; 95% CI, 1.06-1.68; P = 0.013) were significantly increased in patients with DM. However, DM was not associated with increased risk of AFS (HR 1.16; 95% CI, 0.91-1.47; P = 0.238), or loss of primary patency (HR 1.04; 95% CI, 0.79-1.37; P = 0.767).DM and ESRD each independently predict early and late major adverse limb events after an infrainguinal bypass in patients presenting with CLTI. However, in the presence of ESRD, DM may increase perioperative adverse events but does not influence primary patency and AFS at one year. The risk profile associated with ESRD appears to supersede that of DM, with no additive effect.

Purpose To quantify the amount of strain across an anterior cruciate ligament reconstruction (ACLR) before and after a lateral meniscus (LM) posterior root complex tear and determine whether a meniscal root repair effectively protects the ACLR against excessive strain. Methods Fresh-frozen cadaveric knees were tested with an 88-N anterior drawer force and an internal and external torque of 5-Nm applied at 0°, 15°, 30°, 60°, and 90° of flexion. A simulated pivot shift was also applied at 0, 15, and 30° of flexion. Rotation and translation of the tibia, and strain across the ACL graft were recorded. Testing was repeated for the following four conditions: ACL-intact, ACLR with intact LM, ACLR with LM posterior root complex tear, and ACLR with root repair. Results The kinematic data from 12 fresh frozen cadaveric knees underwent analysis. Only 11 specimens had usable strain data. Sectioning the meniscofemoral ligaments and the LM posterior root increased rotational and translational laxity at 30° of knee flexion. ACLR graft strain significantly increased when an anterior load and internal torque were applied. Repair of the LM posterior root reduced strain when the knee was internally rotated but was unable to normalize strain when an anterior force was applied. Conclusions This cadaveric biomechanical study suggests injury to the LM posterior root complex increases rotational and anterior laxity of the knee and places increased strain across reconstructed ACL grafts. Subsequent root repair did not result in a statistically significant reduction in strain. Clinical Relevance This study provides quantitative data on the implications of a LM posterior root injury in the setting of an ACL reconstruction to help guide clinical decision-making.

Antegrade superficial femoral artery (SFA) access for peripheral artery disease reduces the time, radiation, and contrast required with contralateral common femoral access (CFA). Yet, this technique remains underutilized in the treatment of SFA, popliteal and tibial disease, and there remains limited data on the safety and effectiveness of antegrade SFA access in the outpatient setting.A retrospective review of lower extremity peripheral arterial interventions in our office-based endovascular suite was conducted from 2013 to 2018. Interventions necessitating CFA access such as iliac, common femoral, or deep femoral artery revascularization were excluded (n = 206). In addition, interventions potentially requiring large sheaths not amenable to SFA access (e.g., popliteal aneurysm) were excluded. Relevant demographic and treatment variables including postoperative complications were abstracted.We identified 718 patients, who underwent revascularization of the SFA, popliteal and tibial arteries. Antegrade SFA access was chosen in 448 patients (62.4%) with the remaining 270 patients having retrograde CFA access. Antegrade SFA access was achieved primarily with a 4-French sheath, while a majority of retrograde CFA interventions utilized a 6-French sheath for access (87.7% vs 69.5%, P 0.001). Significantly less fluoroscopy (9.5 vs 16.4 min, P 0.001) and contrast (25.4 vs 38.5 mL, P 0.001) were used during SFA access compared with retrograde access. Technical success was achieved in 93.2% with antegrade SFA vs 94.8% retrograde CFA access (P = 0.42). The overall rate of complications was low for both cohorts (2.7% vs 3.7%, P = 0.78) and there were no statistical differences in access site complications (1.1% vs 1.5%, P = 0.94), hematoma (0.7% vs 1.1%, P = 0.84), and pseudoaneurysm (0.4% vs 0%, P = 0.98) between techniques.Percutaneous antegrade SFA access can be performed safely in the outpatient setting and remains an effective alternative to retrograde CFA access with significantly less utilization of fluoroscopy and contrast.

The grim circumstances of the COVID-19 pandemic have highlighted the need to refine and adapt stroke systems of care. Patients’ care-seeking behaviors have changed due to perceived risks of in-hospital treatment during the pandemic. In response to these challenges, we optimized a recently implemented, novel outpatient approach for the evaluation and management of minor stroke and transient ischemic attack, entitled RESCUE-TIA. This modified approach incorporated telemedicine visits and remote testing, and proved valuable during the pandemic. In this review article, we provide the evidence-based rationale for our approach, describe its operationalization, and provide data from our initial experience.

Introduction: Over the last decade, transcatheter aortic valve replacement (TAVR) has emerged as a treatment option for most patients with severe symptomatic aortic stenosis (AS). With growing indi...

Objectives The purpose of this study was to evaluate tip-to-base intentional laceration of the anterior mitral leaflet to prevent left ventricular outflow tract obstruction (LAMPOON) in patients undergoing transcatheter mitral valve replacement (TMVR) in annuloplasty rings or surgical mitral valves. Background LAMPOON is an effective adjunct to TMVR that prevents left ventricular outflow tract obstruction (LVOTO). Laceration is typically performed from the base to the tip of the anterior mitral leaflet. A modified laceration technique from leaflet tip to base may be effective in patients with a prosthesis that protects the aortomitral curtain. Methods This is a multicenter, 21-patient, consecutive retrospective observational cohort. Patients underwent tip-to-base LAMPOON to prevent LVOTO and leaflet overhang, or therapeutically to lacerate a long anterior mitral leaflet risking or causing LVOTO. Outcomes were compared with findings from patients in the LAMPOON investigational device exemption trial with a prior mitral annuloplasty. Results Twenty-one patients with a annuloplasty or valve prosthesis–protected mitral annulus underwent tip-to-base LAMPOON (19 preventive, 2 rescue). Leaflet laceration was successful in all and successfully prevented or treated LVOTO in all patients. No patients had significant LVOTO upon discharge. There were 2 cases of unintentional aortic valve injury (1 patient underwent emergency transcatheter aortic valve replacement and 1 patient underwent urgent surgical aortic valve replacement). In both cases, the patients had a supra-annular ring annuloplasty, and the retrograde aortic guiding catheter failed to insulate the guidewire lacerating surface from the aortic root. All patients survived to 30 days. Compared with classic retrograde LAMPOON, there was a trend toward shorter procedure time. Conclusions Tip-to-base laceration is a simple, effective, and safe LAMPOON variant applicable to patients with an appropriately positioned mitral annular ring or bioprosthetic valve. Operators should take care to insulate the lacerating surface from adjacent structures.

Cerebrovascular complications among critically ill patients with COVID-19 have yet to be fully characterized. In this retrospective case series from a single academic tertiary care referral center in New York City, we present 12 patients with ischemic or hemorrhagic strokes that were found on imaging after a period of prolonged sedation in the setting of COVID-19 pneumonia. This series demonstrates a pattern of cerebrovascular events clinically masked by deep sedation required for management of COVID-19 related acute respiratory distress syndrome (ARDS). Of the 12 patients included, 10 had ischemic stroke, 4 of which had hemorrhagic conversion, and 2 had primary intracerebral hemorrhage. Ten patients were on therapeutic anticoagulation prior to discovery of their stroke, and the remainder received intermediate dose anticoagulation (in a range between prophylactic and therapeutic levels). Additional studies are needed to further characterize the counterbalancing risks of ischemic and hemorrhagic stroke, as well as the optimal management of this patient population.

The field of interventional cardiology has expanded rapidly. As a result, four evolving areas have evolved – peripheral vascular interventions, structural heart interventions, adult congenital heart intervention, and chronic total occlusion. The complexity of these procedures and the number of devices available has grown rapidly. In addition, the professional and public expectations of procedural success and of minimizing case–avoidance have also grown. Specific issues include volume-outcome relationships, maintaining currency and proficiency, accessibility to specialized procedures, and the need to maintain a fundamental level of expertise in acute coronary interventions.

Objectives Postoperative delirium, associated with negative consequences including longer hospital stays and worse cognitive and physical outcomes, is frequently accompanied by sleep-wake disturbance. Our objective was to evaluate the efficacy and short-term safety of ramelteon, a melatonin receptor agonist, for the prevention of postoperative delirium in older patients undergoing orthopedic surgery. Design A quadruple-masked randomized placebo-controlled trial (Clinical Trials.gov NCT02324153) conducted from March 2017 to June 2019. Setting Tertiary academic medical center. Participants Patients aged 65 years or older, undergoing elective primary or revision hip or knee replacement. Intervention Ramelteon (8 mg) or placebo Measurements Eighty participants were randomized to an oral gel cap of ramelteon or placebo for 3 consecutive nights starting the night before surgery. Trained research staff conducted delirium assessments for 3 consecutive days starting on postoperative day (POD) 0, after recovery from anesthesia, and on to POD2. A delirium diagnosis was based upon DSM-5 criteria determined by expert panel consensus. Results Of 80 participants, five withdrew consent (one placebo, four ramelteon) and four were excluded (four ramelteon) after randomization. Delirium incidence during the 2 days following surgery was 7% (5 of 71) with no difference between the ramelteon versus placebo: 9% (3 of 33) and 5% (2 of 38), respectively. The adjusted odds ratio for postoperative delirium as a function of assignment to the ramelteon treatment arm was 1.28 (95% confidence interval: 0.21–7.93; z-value 0.27; p-value = 0.79). Adverse events were similar between the two groups. Conclusion In older patients undergoing elective primary or revision hip or knee replacement, ramelteon was not efficacious in preventing postoperative delirium.

Background Adult-onset inflammatory syndromes often manifest with overlapping clinical features. Variants in ubiquitin-related genes, previously implicated in autoinflammatory disease, may...

Background Robotic-assistance in endovascular intervention represents a nascent yet promising innovation. Objective To present the first human experience utilizing robotic-assisted angiography in the extracranial carotid circulation. Methods Between March 2019 and September 2019, patients with extracranial carotid circulation pathology presenting to Houston Methodist Hospital were enrolled. Results A total of 6 patients met inclusion criteria: 5 underwent diagnostic angiography only with robotic-assisted catheter manipulation, while 1 underwent both diagnostic followed by delayed therapeutic intervention. Mean age was 51 +/- 17.5 yr. Mean anesthesia time was 158.7 +/- 37.9 min, mean fluoroscopic time was 22.0 +/- 7.3 min, and mean radiation dose was 815.0 +/- 517.0 mGy. There were no technical complications and no clinical deficits postprocedure. None of the cases required conversion to manual neurovascular intervention (NVI). Conclusion Incorporating robotic technology in NVI can enhance procedural technique and diminish occupational hazards. Its application in the coronary and peripheral vascular settings has established safety and efficacy, but in the neurovascular setting, this has yet to be demonstrated. This study presents the first in human feasibility experience of robotic-assisted NVI in the extracranial carotid circulation.

Background Does minor head impact without signs of structural brain damage cause short-term changes in vasogenic edema as measured by an increase apparent diffusion coefficient (ADC) using diffusion weighted imaging? If so, could the increase in vasogenic edema be treated with a vasopressin V1a receptor antagonist? We hypothesized that SRX251, a highly selective V1a antagonist, would reduce vasogenic edema in response to a single minor head impact. Methods Lightly anesthetized male rats were subjected to a sham procedure or a single hit to the forehead using a closed skull, momentum exchange model. Animals recovered in five min and were injected with saline vehicle (n = 8) or SRX251 (n = 8) at 15 min post head impact and again 7−8 hrs later. At 2 h, 6 h, and 24 h post injury, rats were anesthetized and scanned for increases in ADC, a neurological measure of vasogenic edema. Sham rats (n = 6) were exposed to anesthesia and scanned at all time points but were not hit or treated. Images were registered to and analyzed using a 3D MRI rat atlas providing site-specific data on 150 different brain areas. These brain areas were parsed into 11 major brain regions. Results Untreated rats with brain injury showed a significant increase in global brain vasogenic edema as compared to sham and SRX251 treated rats. Edema peaked at 6 h in injured, untreated rats in three brain regions where changes in ADC were observed, but returned to sham levels by 24 h. There were regional variations in the time course of vasogenic edema and drug efficacy. Edema was significantly reduced in cerebellum and thalamus with SRX251 treatment while the basal ganglia did not show a response to treatment. Conclusion A single minor impact to the forehead causes regional increases in vasogenic edema that peak at 6 h but return to baseline within a day in a subset of brain regions. Treatment with a selective V1a receptor antagonist can reduce much of the edema.

Background This study was conducted to determine the current nationwide trends and outcomes of reoperative surgical aortic valve replacement (SAVR) performed for a degenerated bioprosthesis. Methods Data from The Society of Thoracic Surgeons (STS) Adult Cardiac Surgery Database were used. All patients who underwent isolated reoperative SAVR for a degenerated aortic bioprosthesis between January 2012 and December 2016 were included. Patients who had other concomitant cardiac surgery procedures or active endocarditis were excluded. Changes during this period were tracked with trend analyses. Results The number of patients undergoing SAVR for bioprosthetic failure increased substantially between 2012 and 2014 (782 in 2012 to 844 in 2013 and to 900 in 2014; relative change, +7.25%); this trend reversed significantly between 2015 and 2016 (decreased to 873 in 2015 and to 840 in 2016; relative change, −3.4%; P = .005). Patients were older in 2012-2014 (65.80 ± 13.52 years) compared with 2015-2016 (64.45 ± 12.91 years; P = .001). Mean STS-predicted mortality risk score decreased from 4.55% in 2012-2014 to 4.25% in 2015-2016 (P = .001). There was no difference in postoperative stroke (1.80% vs 1.80%, P = .87), renal failure requiring dialysis (2.7% vs 2.8%, P = .69), or operative mortality (3.5% vs 4.0%, P = .36) after reoperative SAVR in 2012-2014 and 2015-2016, respectively. Conclusions The number of patients undergoing SAVR for a degenerated bioprosthesis is decreasing in the United States, particularly among older and high-risk patients. These trends may reflect the adoption of valve-in-valve transcatheter aortic valve replacement for a degenerated bioprosthesis after its United States Food and Drug Administration approval in 2015.

A 70-year-old man with mechanical aortic and mitral valves was admitted with progressive shortness of breath. He was found to have thrombosis of the aortic valve prosthesis. Treatment with intravenous thrombolysis was complicated by an acute coronary syndrome related to coronary embolism. The patient was successfully managed conservatively with long-term anticoagulation. An algorithm for the management of coronary embolism is suggested. (Level of Difficulty: Advanced.), Graphical abstract