The voice and swallowing profile of adults with laryngotracheal stenosis before and after reconstructive surgery: A prospective, descriptive observational study.

OBJECTIVES: Airway reconstruction for laryngo tracheal stenosis (LTS) improves dyspnoea. There is little evidence relating to impact upon voice and swallowing. We explored voice and swallowing outcomes in adults with LTS before and after reconstructive surgery. DESIGN: Outcome measures were collected pre-reconstructive surgery, two-weeks post-surgery and up to 4-6 months post-surgery. SETTING: Tertiary referral centre. PARTICIPANTS: With ethical approval, twenty consecutive adult (≥18 years) LTS patients undergoing airway reconstruction were prospectively recruited. MAIN OUTCOME MEASURES: These included physiological values (maximum phonation time (MPT) and fundamental frequency; penetration aspiration score, residue score), clinician-reported (GRBAS, functional oral intake score, 100ml Water Swallow Test) and patient-reported outcomes (Voice Handicap Index-10, Reflux Symptoms Index, Eating Assessment Tool, Dysphagia Handicap Index). RESULTS: The observational study identified patient-reported and clinician-reported voice and swallow difficulties pre- and post-surgery; median and interquartile range are reported at each time point: Voice Handicap Index-10 23 (8-31); 20.5 (9-33.5), 24.5 (12.5-29); Dysphagia Handicap Index 9 (0-37); 13 (7-44); 15 (4-34); GRBAS grade 1(1-2); 2 (1-2.5); 2(1-2); 100ml Water Swallow Test volume score 16.7 (11.1-20); 14.3 (12.5-16.7); 16.7 (14.3-20.0); 100ml Water Swallow Test capacity score 16.3 ± 9.0; 11.0 ± 4.1; 12.5 ± 2.6. CONCLUSIONS: We present the first prospective data on voice and swallowing outcomes in adults with LTS before and after reconstructive surgery. The variability of the outcomes was higher than expected but importantly, for many the voice and swallow outcomes were not within normal limits before surgery. The clinical value of the study demonstrates the need for individual assessment and management of LTS patients' voice and swallowing.

Cardiogenic shock complicating non-ST-segment elevation myocardial infarction: An 18-year study.

OBJECTIVE: To evaluate the epidemiology and outcomes of non-ST-segment-elevation myocardial infarction-cardiogenic shock (NSTEMI-CS) in the United States. METHODS: Adult (>18 years) NSTEMI-CS admissions were identified using the National Inpatient Sample (2000-2017) and classified by tertiles of admission year (2000-2005, 2006-2011 and 2012-2017). Outcomes of interest included temporal trends of prevalence and in-hospital mortality, use of cardiac procedures, in-hospital mortality, hospitalization costs, and length of stay. RESULTS: In over 7.3 million NSTEMI admissions, CS was noted in 189,155 (2.6%). NSTEMI-CS increased from 1.5% in 2000 to 3.6% in 2017 (adjusted odds ratio 2.03 [95% confidence interval 1.97-2.09]; P < .001). Rates of non-cardiac organ failure and cardiac arrest increased during the study period. Between 2000 and 2017, coronary angiography (43.9%-63.9%), early coronary angiography (13.6%-25.6%), percutaneous coronary intervention (14.8%-31.6%), and coronary artery bypass grafting use (19.0%-25.8%) increased (P < .001). Over the study period, the use of intra-aortic balloon pump remained stable (28.6%-28.8%), and both percutaneous left ventricular assist devices (0%-9.1%) and extra-corporeal membrane oxygenation (0.1%-1.6%) increased (all P < .001). In hospital mortality decreased from 50.2% in 2000 to 32.3% in 2017 (adjusted odds ratio 0.27 [95% confidence interval 0.25-0.29]; P < .001). During the 18-year period, hospital lengths of stay decreased, and hospitalization costs increased. CONCLUSIONS: In the United States, prevalence of CS in NSTEMI has increased 2-fold between 2000 and 2017, while in-hospital mortality has decreased during the study period. Use of coronary angiography and percutaneous coronary intervention increased during the study period.

Not Just Dyspnoea: Swallowing as a Concern for Adults with Laryngotracheal Stenosis Undergoing Airway Reconstruction.

Acquired laryngotracheal stenosis (LTS) is a rare condition causing dyspnea and stridor. Patients often require multiple surgical procedures with no guarantee of a definitive outcome. Difficulty swallowing is a recognised problem associated with LTS and the reconstructive surgeries required to manage the condition. The breathlessness patient's experience impacts on swallowing, and the vulnerable structures of the larynx are implicated during complex surgeries. This leads to dysphagia post-surgery, with some patients experiencing more chronic symptoms depending on the biomechanical impact of the surgery, or a pre-existing dysphagia. Despite this there is limited observational research about the dysphagia associated with LTS, with no exploration of the patient experience. Our aim was to investigate patient experience of living with LTS focussing on dysphagia in order to guide clinical practice. A qualitative study was completed using focus groups and semi-structured interviews with 24 patients who have had reconstructive surgery for LTS. Thematic analysis was used to identify three over-arching themes: The Physical Journey, The Emotional Journey and The Medical Journey. Key sub-themes included the importance of self-management and control, presence of symptoms, benefits of therapy, living with a life-long condition, fear and anxiety, autonomy, medicalisation of normal processes and the dichotomy between staff expertise and complacency. Swallowing was connected to all themes. The results are reviewed with consideration of the wider literature of lived experience particularly in relation to other chronic conditions and those that carry a high symptom burden such as head and neck cancer. Future clinical and research recommendations have been made. Akin to other clinical groups, adults with LTS are keen that management of their swallowing is person-centred and holistic.

Suspension laryngoscopy experiences in a tertiary airway service: A prospective study of 150 procedures.

OBJECTIVES: In most cases, suspension laryngoscopy (SL) is efficient, bloodless and with minimal post-procedure discomfort. We aimed to identify predictive patient factors for acceptable surgical views at SL as well as quantify our tertiary airway unit's complication rates. DESIGN: Prospective cohort study of 150 consecutive microlaryngoscopy procedures involving SL over an 8-month period between November 2019 and July 2020. Patients were assessed preoperatively for pre-existing oral, temporomandibular, dental, pharyngeal or laryngeal pathology, interincisor distance and qualitative gross limitations to neck extension and forward head posture. Intraoperatively, the laryngoscopic view was graded by anaesthetic and surgical teams, and complications were recorded on patient interview in recovery. SETTING: Tertiary adult airway service for predominantly benign pathology. RESULTS: Adequate surgical views were obtained in 149/150 procedures. BMI had a weak positive correlation with a more difficult view (r = .22, p = .008) but did not correlate with a statistically significant increase in any complication. There was a weak negative correlation between age and interincisor gap (r = -.20, p = .014), and wider mouth opening correlated very weakly with a lower incidence of sore throat (r = -.19, p = .023). Gross macroglossia showed a significant moderate positive correlation with tongue symptoms (r = .45, p = 1.611 × 10-8 ). CONCLUSION: In the context of an experienced airway unit with a high caseload of predominantly benign pathology, SL is very effective and safe with low associated morbidity and no mortality. The most common complication of SL is temporary sore throat and there remain recognised risks of temporary tongue and dental symptoms.

Remote robotic percutaneous coronary intervention: An animal feasibility study.

OBJECTIVES: The purpose of this study was to explore the feasibility and safety of robotic PCI performed using an off-siteremote-control system in an animal model. BACKGROUND: Access to primary percutaneous coronary intervention (PCI) remains a challenge in acute myocardial infarction management. The combination of telemedicine and robotic PCI allow the potential delivery of primary PCI to remote locations without the delay of transfer. METHODS: This single-center prospective pilot preclinical feasibility study compared robotic PCI with remote PCI on swine across three stages (adjacent room, different floor of the same building, two different buildings). Latency up to 1,000 ms was introduced into the operating environment to simulate decreased network quality (blinded to operator). The primary outcome measures were technical success and acute safety. The secondary outcome measures included lesion wiring time, procedural time and qualitative scoring of the PCI experience by the operator. RESULTS: Across 52 experiments in 15 animals, technical success was 100%. No procedural complications occurred during the study. No significant difference in lesion treatment time was detected between stages (p = .11) and between time per target vessel when latency up to 1,000 ms was introduced (p = .58). Injected delay >250 ms had the greatest impact on procedure perceived lag. Longer procedure time was associated with lower procedure impact score, regardless of injected latency. CONCLUSIONS: Remote robotic PCI was feasible and safe in an animal model. Procedural duration was acceptable and unaffected by network latency. Future studies are needed to determine the safety and feasibility of remote PCI in humans.

An Algorithm for Pairing Interventionalists and Surgeons for the TAVR Procedure.

The Transcatheter Aortic Valve Replacement (TAVR) procedure requires an initial consultation and a subsequent procedure by an interventionalist (IC) and surgeon. The IC-surgeon pair coordination is extremely challenging, especially at Mayo Clinic due to provider time commitments distributed across practice, research, and education activities. Current practice aims to establish the coordination manually, resulting in a scheduling process that is cumbersome and time consuming for the schedulers. We develop an algorithm for pairing ICs and surgeons that minimizes the lead time (days elapsed between the clinic consult and procedure). As compared to current practice, this algorithm is able to reduce average lead time by 59% and increase possible IC-surgeon pairs by 7%. The proposed algorithm is shown to be flexible enough to incorporate practice variations such as lead time upper bound and two procedure days for a single consult day. Algorithm alternatives are also presented for practices who may find the proposed algorithm infeasible for their practice.

Characteristics and long term outcomes of patients with acute coronary syndromes due to culprit left main coronary artery disease treated with percutaneous coronary intervention.

BACKGROUND: Patients with acute coronary syndrome (ACS) due to unprotected culprit left main coronary artery disease (LMCAD) treated with percutaneous coronary intervention (PCI) are rare, high-risk, and not represented in trials. Data regarding long term outcome after PCI are limited. METHODS: Between January 2000 and December 2014, there were 8,794 patients hospitalized with unstable angina/non-ST elevation myocardial infarction (UA/NSTEMI) or ST-elevation myocardial infarction (STEMI) treated with PCI at our institution; of these, 83 (0.94%) patients were identified as having culprit LMCAD ACS. RESULTS: Of the 83 patients with unprotected LMCAD ACS, 40 patients presented with STEMI and 43 patients presented with UA/NSTEMI. As compared to LM UA/NSTEMI, LM STEMI patients were younger and had less hypertension, with a trend towards greater frequency of cardiogenic shock. Distal LM involvement was common in both groups and did not differ by ACS type. In-hospital mortality was 33% in LM STEMI and 9% in LM UA/NSTEMI (P = .009). Over median follow up of 6.3 years, long term survival rates in both groups were similar (46% for STEMI vs 51% for UA/NSTEMI; P = .50 by log-rank). CONCLUSIONS: Unprotected culprit LMCAD ACS necessitating PCI is uncommon, occurring in <1% of cases, but is associated with reduced survival, with long term follow-up noting continued and similar risk of death regardless of index ACS type.

Predictors of 1-year mortality after transcatheter aortic valve replacement.

OBJECTIVE: To identify variables predictive of increased mortality within 1 year of transcatheter aortic valve replacement (TAVR). METHODS: We retrospectively reviewed the records of 723 consecutive patients who received TAVR from November 2008 through April 2016. Patient and procedure-related characteristics were analyzed with logistic regression for an association with death within 1 year of TAVR. RESULTS: Patient mean age was 81 ± 9 years, male sex was present in 428 patients (59%), and STS predicted risk of mortality was 9.2 ± 6.2%. There were 107 deaths (15%) within 1 year of operation. Multivariable analysis identified increased risk of death with severe chronic lung disease (odds ratio [OR] 2.01; 95% confidence interval [CI] 1.23-3.29; P = 0.006), severe tricuspid valve regurgitation (OR 2.35; 95%CI 1.17-4.30; P = 0.017), vascular injury (OR 2.23; 95%CI 1.15-4.30; P = 0.017), and new-onset dialysis (OR 8.49; 95%CI 3.00-24.03; P < 0.001) (Area under the curve 0.687). When stratified by arterial access, there was increased risk of death following severe tricuspid valve regurgitation, vascular injury, or new-onset dialysis for transfemoral access and severe chronic lung disease or new-onset dialysis for alternative access. CONCLUSION: Patient characteristics and procedure-related complications are both significantly associated with increased risk of death within 1 year of TAVR. Patients with the baseline findings of severe chronic lung disease or severe tricuspid valve regurgitation may not experience mortality benefit from TAVR, and they should be assessed and counselled accordingly. Avoiding procedure-related complications is paramount to a good outcome. The findings have important implications for health care delivery services.

Percutaneous revascularization in patients treated with thoracic radiation for cancer.

OBJECTIVES: To assess coronary revascularization outcomes in patients with previous thoracic radiation therapy (XRT). BACKGROUND: Previous chest radiation has been reported to adversely affect long term survival in patients with coronary disease treated with percutaneous coronary interventions (PCI). METHODS: Retrospective, single center cohort study of patients previously treated with thoracic radiation and PCI. Patients were propensity matched against control patients without radiation undergoing revascularization during the same time period. RESULTS: We identified 116 patients with radiation followed by PCI (XRT-PCI group) and 408 controls. Acute procedural complications were similar between groups. There were no differences in all-cause and cardiac mortality between groups (all-cause mortality HR 1.31, P=.078; cardiac mortality 0.78, P=.49). CONCLUSION: Patients with prior thoracic radiation and coronary disease treated with PCI have similar procedural complications and long term mortality when compared to control subjects.

Magnetizable stent-grafts enable endothelial cell capture.

Emerging nanotechnologies have enabled the use of magnetic forces to guide the movement of magnetically-labeled cells, drugs, and other therapeutic agents. Endothelial cells labeled with superparamagnetic iron oxide nanoparticles (SPION) have previously been captured on the surface of magnetizable 2205 duplex stainless steel stents in a porcine coronary implantation model. Recently, we have coated these stents with electrospun polyurethane nanofibers to fabricate prototype stent-grafts. Facilitated endothelialization may help improve the healing of arteries treated with stent-grafts, reduce the risk of thrombosis and restenosis, and enable small-caliber applications. When placed in a SPION-labeled endothelial cell suspension in the presence of an external magnetic field, magnetized stent-grafts successfully captured cells to the surface regions adjacent to the stent struts. Implantation within the coronary circulation of pigs (n=13) followed immediately by SPION-labeled autologous endothelial cell delivery resulted in widely patent devices with a thin, uniform neointima and no signs of thrombosis or inflammation at 7 days. Furthermore, the magnetized stent-grafts successfully captured and retained SPION-labeled endothelial cells to select regions adjacent to stent struts and between stent struts, whereas the non-magnetized control stent-grafts did not. Early results with these prototype devices are encouraging and further refinements will be necessary in order to achieve more uniform cell capture and complete endothelialization. Once optimized, this approach may lead to more rapid and complete healing of vascular stent-grafts with a concomitant improvement in long-term device performance.

Experience and complications associated with use of guide extension catheters in percutaneous coronary intervention.

OBJECTIVES: To investigate the utility and safety of the GuideLiner "mother-and-child" catheter system during transradial and transfemoral percutaneous coronary intervention (PCI). BACKGROUND: In patients with complex coronary anatomy, stent delivery can be challenging and result in procedural failure and complications. The GuideLiner is a coaxial guide extension system designed to enable deep vessel engagement and facilitate device delivery. The purpose of this study was to evaluate procedural success and safety in a series of GuideLiner-facilitated PCI. METHODS: Single center retrospective study of PCI utilizing the GuideLiner catheter between February 2010 and October 2014. Patients who underwent PCI without GuideLiner use during the same time period were used as controls for comparison. RESULTS: A total of 363 cases of GuideLiner-facilitated PCI were identified from 6,088 unique PCI procedures performed during this same time period. Patients in the GuideLiner group were older (mean age 71.5 vs. 67.8, P < 0.001) and had more multivessel disease (72% vs. 63%, P = 0.001) compared with controls. Type C lesions were present in 78% of GuideLiner cases. Procedural success resulting in successful device delivery with the GuideLiner catheter was 80.2%. Stent deformation associated with GuideLiner use occurred in 2.2% (8/363), with the incidence of this complication decreasing over device iterations. Coronary dissection attributed to GuideLiner occurred in 3.3% (12/363) and became less frequent over the study period. CONCLUSIONS: In this consecutive series of GuideLiner supported PCI, the guide extension system enabled procedural success in the majority. A decline in device-associated complications over time may be attributed to operator learning curve, patient selection, and improvement in catheter design. © 2015 Wiley Periodicals, Inc.

Cardiac AAV9 Gene Delivery Strategies in Adult Canines: Assessment by Long-term Serial SPECT Imaging of Sodium Iodide Symporter Expression.

Heart failure is a leading cause of morbidity and mortality, and cardiac gene delivery has the potential to provide novel therapeutic approaches. Adeno-associated virus serotype 9 (AAV9) transduces the rodent heart efficiently, but cardiotropism, immune tolerance, and optimal delivery strategies in large animals are unclear. In this study, an AAV9 vector encoding canine sodium iodide symporter (NIS) was administered to adult immunocompetent dogs via epicardial injection, coronary infusion without and with cardiac recirculation, or endocardial injection via a novel catheter with curved needle and both end- and side-holes. As NIS mediates cellular uptake of clinical radioisotopes, expression was tracked by single-photon emission computerized tomography (SPECT) imaging in addition to Western blot and immunohistochemistry. Direct epicardial or endocardial injection resulted in strong cardiac expression, whereas expression after intracoronary infusion or cardiac recirculation was undetectable. A threshold myocardial injection dose that provides robust nonimmunogenic expression was identified. The extent of transmural myocardial expression was greater with the novel catheter versus straight end-hole needle delivery. Furthermore, the authors demonstrate that cardiac NIS reporter gene expression and duration can be quantified using serial noninvasive SPECT imaging up to 1 year after vector administration. These data are relevant to efforts to develop cardiac gene delivery as heart failure therapy.

Ectopic Immature Renal Tissue Associated with Lipomeningomyelocele and Enteric Duplication Cyst: A Report of Two Cases.

Ectopic immature renal tissue (EIRT) is a lesion rarely described in the literature. It shows the components of a nephrogenic rest including the blastema, epithelia, and stroma. We report two cases of EIRT in a 3-year-old female and an 8 months male child, associated with lipomeningomyelocele and an enteric duplication cyst, respectively, along with detailed immunohistochemical profile. Though there are a few cases of EIRT associated with teratoma, only two cases of EIRT associated with lipomeningomyelocele have been described in the English literature. Moreover, extensive literature search did not reveal any previous case report where EIRT had been documented in an enteric duplication cyst.

Long-term Outcomes of Rituximab Therapy in Ocular Granulomatosis with Polyangiitis: Impact on Localized and Nonlocalized Disease.

PURPOSE: To evaluate the long-term outcomes of rituximab (RTX) treatment in patients with ocular granulomatosis with polyangiitis (GPA) with localized or generalized disease. DESIGN: Retrospective cohort. PARTICIPANTS: Thirty-seven patients with ocular GPA receiving RTX in a multidisciplinary vasculitis clinic between 2004 and 2013. METHODS: A total of 100 patients who received a course of RTX were identified, and notes were reviewed. Baseline demographic details, clinical characteristics (including organ involvement), drugs used, and outcome measures were recorded. MAIN OUTCOME MEASURES: The percentage in remission (inactive disease with prednisolone ≤7.5 mg with or without maintenance treatment) at 6 months, time to remission, percentage relapsing, side effects, B-cell count, antineutrophil cytoplasm antibody titers, induction, and maintenance regimens. RESULTS: The median follow-up time after the first RTX course was 36.5 months. Twenty patients had scleritis, and 17 patients had orbital disease; 86% achieved remission at 6 months. The percentage in remission versus partial remission was not statistically significant between patients with scleritis and patients with orbital disease (85% vs. 15% with scleritis and 82% vs. 18% with orbital disease; P = 1.00). The percentage relapsing was not statistically significant (P = 0.33) between scleritis (60%) and orbital disease (41%). Localized disease (ocular ± ear-nose-throat/lung) was observed in 57%, and generalized disease (ocular plus other organs) was observed in 43%, the former having a median duration of disease of 40 months. There was no statistically significant difference (P = 0.37) in the percentage in remission between localized and generalized ocular disease. Relapses occurred in 51%, with localized disease being a significant risk factor for relapse. Fifty percent of patients with generalized disease versus none with localized disease received cyclophosphamide (CYP) as part of the induction regimen. Patients who received CYP during induction had significantly (P = 0.027) lower ratios of baseline 12-month proteinase 3 titers than patients who did not have CYP. Infections were observed in 16% of patients, with 8% requiring hospital admission. CONCLUSIONS: Our long-term data suggest that RTX is effective for inducing disease remission in localized and generalized ocular GPA. Localized disease is a significant risk factor for relapse, which may be related to less use of CYP in the induction regimen.

Three dimensional quantitative coronary angiography can detect reliably ischemic coronary lesions based on fractional flow reserve.

Conventional coronary angiography (CAG) has limitations in evaluating lesions producing ischemia. Three dimensional quantitative coronary angiography (3D-QCA) shows reconstructed images of CAG using computer based algorithm, the Cardio-op B system (Paieon Medical, Rosh Ha'ayin, Israel). The aim of this study was to evaluate whether 3D-QCA can reliably predict ischemia assessed by myocardial fractional flow reserve (FFR) < 0.80. 3D-QCA images were reconstructed from CAG which also were evaluated with FFR to assess ischemia. Minimal luminal diameter (MLD), percent diameter stenosis (%DS), minimal luminal area (MLA), and percent area stenosis (%AS) were obtained. The results of 3D-QCA and FFR were compared. A total of 266 patients was enrolled for the present study. FFR for all lesions ranged from 0.57 to 1.00 (0.85 ± 0.09). Measurement of MLD, %DS, MLA, and %AS all were significantly correlated with FFR (r = 0.569, 0609, 0.569, 0.670, respectively, all P < 0.001). In lesions with MLA < 4.0 mm(2), %AS of more than 65.5% had a 80% sensitivity and a 83% specificity to predict FFR < 0.80 (area under curve, AUC was 0.878). 3D-QCA can reliably predict coronary lesions producing ischemia and may be used to guide therapeutic approach for coronary artery disease.

Magnetic navigation facilitates percutaneous coronary intervention for complex lesions.

BACKGROUND: We sought to determine the utility of a magnetic navigation system (MNS) in treating a variety of coronary artery lesions including those that could not be revascularized with standard percutaneous coronary intervention (PCI). MNS may add value in the treatment of tortuous arteries and bifurcation lesions; however its widespread adoption has lagged because of cost and a lack of clear advantage over conventional PCI. We performed a retrospective analysis to determine whether MNS improved procedural success for highly complex lesions. METHODS AND RESULTS: One hundred and forty-eight patients underwent treatment with MNS at Mayo Clinic, Rochester. Clinical data, angiographic and procedural characteristics, lesion crossing success and outcomes were reviewed. Overall 133 patients underwent successful revascularization with 87% (143) of 164 lesions crossed using MNS alone. Another six lesions required a combination of MNS and conventional devices resulting in overall success of 91% (149/164). Eighteen complex lesions had previously failed PCI and 12 (67%) were successfully treated with MNS. Success after failed PCI was higher (88%) when a frequent user operated MNS, but occasional users also noted incremental success (30%). Twenty-five chronic total occlusions were included amongst these 164 lesions, with observed antegrade MNS lesion crossing rates of 78% for regular and 14% for occasional users. CONCLUSIONS: MNS is a useful adjunct to performance of PCI. This specialized technology has a clear learning curve and can facilitate treatment of highly complex lesions.

Long-term Stroke and Mortality Risk in Nonagenarians After Transcatheter Aortic Valve Insertion.

BACKGROUND: Limited data exist on the long-term outcomes of transcatheter aortic valve insertion (TAVI) in nonagenarian patients. This study investigated the relationship between patient baseline comorbidity and frailty on the long-term outcome of the nonagenarian population. METHODS: A retrospective analysis was conducted of 187 consecutive nonagenarian patients who underwent TAVI from 2009 to 2020. Multivariable models were used to analyze the association between baseline patient and frailty variables and mortality, stroke, and repeat hospitalization. Long-term survival was compared with an age- and sex-matched United States population. RESULTS: The median Society of Thoracic Surgeons predicted risk of mortality was 10% (interquartile range, 7%-17%). Frailty was met in 72% of patients based on the 5-meter walk test, 13% based on the Kansas City Cardiomyopathy Questionnaire 12-item instrument score, 12% based on Katz Index of Independence in Activities of Daily Living, and 8% based on serum albumin levels. Procedure-related death occurred in 3 patients (2%) and stroke in 8 (4%). The median duration of follow-up was 3.4 years. Outcomes included death in 150 patients (80%), stroke in 15, and repeat hospitalization in 114. Multivariable analysis identified no association between any of the baseline patient variables with mortality, stroke, repeat hospitalization, or the combined outcomes (all P > .05). The 1- and 5-year survival rates in TAVI-treated nonagenarians were similar to age- and sex-matched controls (P = .27). CONCLUSIONS: Long-term death or stroke is independent of The Society of Thoracic Surgeons predicted risk of mortality and frailty risk variables in this nonagenarian patient population who received TAVI. Furthermore, survival is similar to age- and sex-matched controls.

Identification of a monocyte-predisposed hierarchy of hematopoietic progenitor cells in the adventitia of postnatal murine aorta.

BACKGROUND: Hematopoiesis originates from the dorsal aorta during embryogenesis. Although adult blood vessels harbor progenitor populations for endothelial and smooth muscle cells, it is not known if they contain hematopoietic progenitor or stem cells. Here, we hypothesized that the arterial wall is a source of hematopoietic progenitor and stem cells in postnatal life. METHODS AND RESULTS: Single-cell aortic disaggregates were prepared from adult chow-fed C57BL/6 and apolipoprotein E-null (ApoE(-/-)) mice. In short- and long-term methylcellulose-based culture, aortic cells generated a broad spectrum of multipotent and lineage-specific hematopoietic colony-forming units, with a preponderance of macrophage colony-forming units. This clonogenicity was higher in lesion-free ApoE(-/-) mice and localized primarily to stem cell antigen-1-positive cells in the adventitia. Expression of stem cell antigen-1 in the aorta colocalized with canonical hematopoietic stem cell markers, as well as CD45 and mature leukocyte antigens. Adoptive transfer of labeled aortic cells from green fluorescent protein transgenic donors to irradiated C57BL/6 recipients confirmed the content of rare hematopoietic stem cells (1 per 4 000 000 cells) capable of self-renewal and durable, low-level reconstitution of leukocytes. Moreover, the predominance of long-term macrophage precursors was evident by late recovery of green fluorescent protein-positive colonies from recipient bone marrow and spleen that were exclusively macrophage colony-forming units. Although trafficking from bone marrow was shown to replenish some of the hematopoietic potential of the aorta after irradiation, the majority of macrophage precursors appeared to arise locally, suggesting long-term residence in the vessel wall. CONCLUSIONS: The postnatal murine aorta contains rare multipotent hematopoietic progenitor/stem cells and is selectively enriched with stem cell antigen-1-positive monocyte/macrophage precursors. These populations may represent novel, local vascular sources of inflammatory cells.