Two-year clinical outcomes after successful transcatheter aortic valve implantation with balloon-expandable versus self-expanding valves: A subanalysis of the GALILEO trial.

BACKGROUND: Midterm data comparing clinical outcomes after successful implantation of self-expanding and balloon-expandable transcatheter heart valves (THV) are limited. We aimed to compare 2-year outcomes after successful transcatheter aortic valve implantation (TAVI) with the Edwards balloon-expandable or the Medtronic self-expanding THV. METHODS: Two-year outcomes were analyzed according to the implanted THV in the GALILEO trial. Major adverse cardiac and cerebrovascular events (MACCE) was a composite of all-cause death or thromboembolic events including stroke, myocardial infarction, symptomatic valve thrombosis, systemic embolism, deep-vein thrombosis, or pulmonary embolism. RESULTS: Among 1644 patients recruited in 136 centers across 16 countries between 2015 and 2018, 499 received a self-expanding and 757 patients received a balloon-expandable THV. Patients treated with a self-expanding THV were more likely to be female, and had higher surgical risk, lower hemoglobin levels, and more frequent valve-in-valve procedures than those with a balloon-expandable THV. After multivariable adjustment, there were no significant differences in major clinical outcomes between self-expanding versus balloon-expandable THV: MACCE (17.0% vs. 13.4%, adjusted-hazard ratios [HR] 1.18, 95% confidence intervals [CI]: 0.82-1.69); all-cause death (11.4% vs. 9.3%, adjusted-HR 1.26; 95% CI: 0.78-2.05); cardiovascular death (8.5% vs. 4.0%, adjusted-HR 1.53; 95% CI: 0.82-2.86), any stroke (5.1% vs. 3.7%, adjusted-HR 0.86; 95% CI: 0.43-1.73); major or life-threatening bleeding (5.9% vs. 6.8%, adjusted-HR 0.93; 95% CI: 0.53-1.63). CLINICAL TRIAL REGISTRATION: https://www. CLINICALTRIALS: gov. NCT02556203. CONCLUSIONS: Two-year follow-up data from the GALILEO trial indicate that successful TAVI either with self-expanding or balloon-expandable THVs according to physician discretion did not show difference in rates of MACCE.

Fifteen-minute consultation: Childhood rumination syndrome.

Rumination syndrome is a functional bowel disorder where stomach contents effortlessly regurgitate into the mouth. It is an entirely separate entity to gastro-oesophageal reflux disease and requires behavioural rather than pharmaceutical management. Symptoms usually respond well to treatment, though in extreme cases, patients may experience significant weight loss and require inpatient admission.

The role of diabetes mellitus in the composition of coronary thrombi in patients presenting with acute ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention.

BACKGROUND: Although diabetes mellitus (DM) is a predictor of poor outcomes in patients with ST-segment elevation myocardial infarction (STEMI), few studies have analyzed the impact of DM on the constituency of coronary thrombi. OBJECTIVES: Comparing morphologic and histopathologic aspects of coronary thrombi in STEMI patients with and without DM who underwent primary percutaneous coronary intervention. METHODS: All consecutive patients with STEMI admitted to our institution between April 2010 and December 2012 (n = 1,548) were considered for inclusion. Thrombus material was obtained by aspiration thrombectomy; morphologic and histopathologic aspects were assessed by 3 independent pathologists blinded to clinical characteristics and outcomes. Patients with DM were compared with those without DM. A sensitivity analysis was performed using a propensity score. RESULTS: During the study period, coronary thrombi material from 259 patients was obtained, of whom 19% (n = 49) had diabetes. Diabetic patients were older (P = .10), had a higher frequency of hypertension (P < .01) and dyslipidemia (P = .03), and had a trend to a longer time from the onset of chest pain to hospital arrival (P = .08). The number of retrieved fragments, the size of the thrombi and its composition (leukocytes, fibrin, and erythrocytes percent), and thrombus age and color were similar between patients with or without DM. There were also no statistically significant differences in thrombus constituency of the propensity score-matched patients (n = 92). CONCLUSIONS: In this study, morphologic and histopathologic constituency of coronary thrombi in the setting of a ST-elevation myocardial infarction was not significantly different between patients with or without DM. This finding was intriguing and deserves further investigation.

Epithelial attachment and downgrowth on dental implant abutments--a comprehensive review.

UNLABELLED: The soft tissues around dental implants are enlarged compared with the gingiva because of the longer junctional epithelium and the hemidesmosonal attachments are fewer, suggestive of a poorer quality attachment. Inflammatory infiltrates caused by bacterial colonization of the implant-abutment interface are thought to be one of the factors causing epithelial downgrowth and subsequent peri-implant bone loss. Gold alloys and dental ceramics as well as the contamination of the implant surface with amino alcohols, appear to promote epithelial downgrowth. Physical manipulaton of the abutment surfaces, including concave abutment designs, platform switching, and microgrooved surfaces are believed to inhibit epithelial downgrowth and minimizes bone loss at the implant shoulder. This paper reviews the factors that are believed to influence the migration of epithelial attachment the dental implant and abutment surfaces. Exploration of innovative computer-aided design/computer-aided manufacturing-based concepts such as "one abutment-one time" and their effect on epithelial downgrowth are discussed. CLINICAL SIGNIFICANCE: Based on the review of current literature, the authors recommend inserting definitive abutments at the time of surgical uncovering. To implement this concept, registration of the implant position should to be taken at the time of surgical implant placement.

Data-driven automated classification algorithms for acute health conditions: applying PheNorm to COVID-19 disease.

OBJECTIVES: Automated phenotyping algorithms can reduce development time and operator dependence compared to manually developed algorithms. One such approach, PheNorm, has performed well for identifying chronic health conditions, but its performance for acute conditions is largely unknown. Herein, we implement and evaluate PheNorm applied to symptomatic COVID-19 disease to investigate its potential feasibility for rapid phenotyping of acute health conditions. MATERIALS AND METHODS: PheNorm is a general-purpose automated approach to creating computable phenotype algorithms based on natural language processing, machine learning, and (low cost) silver-standard training labels. We applied PheNorm to cohorts of potential COVID-19 patients from 2 institutions and used gold-standard manual chart review data to investigate the impact on performance of alternative feature engineering options and implementing externally trained models without local retraining. RESULTS: Models at each institution achieved AUC, sensitivity, and positive predictive value of 0.853, 0.879, 0.851 and 0.804, 0.976, and 0.885, respectively, at quantiles of model-predicted risk that maximize F1. We report performance metrics for all combinations of silver labels, feature engineering options, and models trained internally versus externally. DISCUSSION: Phenotyping algorithms developed using PheNorm performed well at both institutions. Performance varied with different silver-standard labels and feature engineering options. Models developed locally at one site also worked well when implemented externally at the other site. CONCLUSION: PheNorm models successfully identified an acute health condition, symptomatic COVID-19. The simplicity of the PheNorm approach allows it to be applied at multiple study sites with substantially reduced overhead compared to traditional approaches.

Changing strategies of the retrograde approach for chronic total occlusion during the past 7 years.

OBJECTIVE: We reviewed the technical changes and results achieved with the retrograde approach since we introduced it 7 years ago. SUBJECTS AND METHODS: The subjects were 1,268 patients who were treated for CTO between January 2004 and December 2010. They were investigated with respect to the success rate, the frequency of employing the retrograde approach and its outcome, and other factors. RESULTS: The retrograde approach was employed in ∼30% of chronic total occlusion (CTO) patients (n = 281) and the retrograde guidewire success rate was 81.1%. The kissing wire technique was substituted for the retrograde approach in 126 of the 281 patients, with antegrade crossing of a guidewire being successful in 88 of them (70%). The retrograde approach was combined with the CART and reverse controlled antegrade retrograde tracking (CART) techniques in 22 and 21 patients, respectively. Among 83 patients treated with Corsair catheters, crossing of the CTO was achieved in 63. The overall procedural success rate was 79.7% (224 patients). Complications of the retrograde approach included collateral channel dissection (2.1%), channel perforation (1.7%), CTO perforation (1.7%), and donor artery occlusion (1.1%). CONCLUSION: The success rate and safety of the retrograde approach are both satisfactory if the appropriate devices and techniques are selected.

The Association of Organizational Readiness With Lung Cancer Screening Utilization.

INTRODUCTION: Lung cancer screening is widely underutilized. Organizational factors, such as readiness for change and belief in the value of change (change valence), may contribute to underutilization. The aim of this study was to evaluate the association between healthcare organizations' preparedness and lung cancer screening utilization. METHODS: Investigators cross-sectionally surveyed clinicians, staff, and leaders at10 Veterans Affairs from November 2018 to February 2021 to assess organizational readiness to implement change. In 2022, investigators used simple and multivariable linear regression to evaluate the associations between facility-level organizational readiness to implement change and change valence with lung cancer screening utilization. Organizational readiness to implement change and change valence were calculated from individual surveys. The primary outcome was the proportion of eligible Veterans screened using low-dose computed tomography. Secondary analyses assessed scores by healthcare role. RESULTS: The overall response rate was 27.4% (n=1,049), with 956 complete surveys analyzed: median age of 49 years, 70.3% female, 67.6% White, 34.6% clinicians, 61.1% staff, and 4.3% leaders. For each 1-point increase in median organizational readiness to implement change and change valence, there was an associated 8.4-percentage point (95% CI=0.2, 16.6) and a 6.3-percentage point increase in utilization (95% CI= -3.9, 16.5), respectively. Higher clinician and staff median scores were associated with increased utilization, whereas leader scores were associated with decreased utilization after adjusting for other roles. CONCLUSIONS: Healthcare organizations with higher readiness and change valence utilized more lung cancer screening. These results are hypothesis generating. Future interventions to increase organizations' preparedness, especially among clinicians and staff, may increase lung cancer screening utilization.

Characterization of quantitative flow ratio and fractional flow reserve discordance using doppler flow and clinical follow-up.

The physiological mechanisms of quantitative flow ratio and fractional flow reserve disagreement are not fully understood. We aimed to characterize the coronary flow and resistance profile of intermediate stenosed epicardial coronary arteries with concordant and discordant FFR and QFR. Post-hoc analysis of the DEFINE-FLOW study. Anatomical and Doppler-derived physiological parameters were compared for lesions with FFR+QFR- (n = 18) vs. FFR+QFR+ (n = 43) and for FFR-QFR+ (n = 34) vs. FFR-QFR- (n = 139). The association of QFR results with the two-year rate of target vessel failure was assessed in the proportion of vessels (n = 195) that did not undergo revascularization. Coronary flow reserve was higher [2.3 (IQR: 2.1-2.7) vs. 1.9 (IQR: 1.5-2.4)], hyperemic microvascular resistance lower [1.72 (IQR: 1.48-2.31) vs. 2.26 (IQR: 1.79-2.87)] and anatomical lesion severity less severe [% diameter stenosis 45.5 (IQR: 41.5-52.5) vs. 58.5 (IQR: 53.1-64.0)] for FFR+QFR- lesions compared with FFR+QFR+ lesions. In comparison of FFR-QFR+ vs. FFR-QFR- lesions, lesion severity was more severe [% diameter stenosis 55.2 (IQR: 51.7-61.3) vs. 43.4 (IQR: 35.0-50.6)] while coronary flow reserve [2.2 (IQR: 1.9-2.9) vs. 2.2 (IQR: 1.9-2.6)] and hyperemic microvascular resistance [2.34 (IQR: 1.85-2.81) vs. 2.57 (IQR: 2.01-3.22)] did not differ. The agreement and diagnostic performance of FFR using hyperemic stenosis resistance (> 0.80) as reference standard was higher compared with QFR and coronary flow reserve. Disagreement between FFR and QFR is partly explained by physiological and anatomical factors. Clinical Trials Registration https://www.clinicaltrials.gov ; Unique identifier: NCT01813435. Changes in central physiological and anatomical parameters according to FFR and QFR match/mismatch quadrants.

Shear bond strengths of pressed and layered veneering ceramics to high-noble alloy and zirconia cores.

STATEMENT OF PROBLEM: Heat-pressed ceramics to metal alloys and zirconia have been available for some time. However, information regarding their shear bond strengths is limited. PURPOSE: The purpose of this study was to evaluate the shear bond strengths of heat-pressed and layered ceramics with regard to their corresponding high-noble alloy and zirconia cores. MATERIAL AND METHODS: Forty cylinders (approx. 5 mm in diameter) of high-noble alloy (Olympia) were cast and divided into 4 groups (n=10). Metal cylinders were veneered with ceramics to produce shear test specimens: Group PMI with IPS InLine POM; Group LMI with IPS InLine; Group PMC with Pulse press-to-metal; and Group LMC with Authentic Pulse Metal ceramic. Forty cylinders (approx. 5 mm in diameter) of zirconia (Lava) were obtained and divided into 4 groups (n=10). These cylinders were veneered with ceramics to produce shear test specimens: Group PZI with IPS e.max ZirPress; Group LZI with IPS e.max. Ceram; Group PZV with VITA PM9; and Group LZV with VITA VM9. The veneering ceramics, 3 mm in thickness, were either pressed or layered to their corresponding cylinders. Thermal cycling was performed at 5°C and 55°C for 20,000 cycles with a 20 second dwell time. Shear bond strength testing was conducted in a universal testing machine, and the failure strengths were recorded. Fracture surfaces were characterized visually, under a stereomicroscope, and with a scanning electron microscope (SEM). Data were analyzed using rank-based Kruskal-Wallis and Mann-Whitney tests with Bonferroni correction to adjust for multiple comparisons (α=.05). RESULTS: For metal ceramic specimens, the mean (SD) shear bond strengths ranged from 37.8 (20.6) MPa to 66.4 (22.1) MPa. There were significant differences between Groups PMI and PMC and between Groups LMI and PMC, in which Groups PMI and LMI had significantly higher strength values than Group PMC (P=.041). For zirconia ceramic specimens, the mean (SD) shear bond strengths ranged from 30.03 (9.49) MPa to 47.2 (13.0) MPa, with Group LZV having a significantly higher shear bond strength value than Group LZI (P=.012). Half of the Group PZV specimens failed during thermal cycling, and Group PZV was, therefore, excluded from statistical analysis. For all shear bond strength testing specimens, cohesive failures in the veneering ceramics were observed. CONCLUSIONS: For shear bond strength of veneering ceramics to high-noble alloy, there was no significant difference between pressing and layering with the same manufacturer. For shear bond strength of veneering ceramics to zirconia, there was no significant difference between the pressed and layered groups.

Interdisciplinary treatment of cervical lesions.

Soft tissue grafting is an integral part of treatment of cervical lesions due to the common lack of adequate attached gingiva and root exposure associated with these lesions. Complete root coverage is a predictable outcome for Miller Class I and II recession defects, and partial root coverage can be achieved in Miller Class III defects. In the esthetic zone, it is desirable to cover as much of the root as possible, and all sites require an adequate zone of attached gingiva, especially adjacent to a restoration. Restorations are required for cervical lesions with excessive depth and significant involvement of the enamel, but they should be avoided where the lesion is shallow and the enamel involvement is minimal. Of course, some sites will require both soft-tissue grafting and placement of a restoration. An interdisciplinary approach to treating cervical lesions will create the most biologically appropriate, stable, and esthetic outcome. Establishing the appropriate tooth form first in treatment planning and sequencing will determine the gingival level and extent of periodontal procedures necessary to achieve the desired outcome.

Development and growth of anterior spine surgery in Minnesota.

Until the 1960s, it was not possible to directly access the thoracic vertebrae in order to correct conditions such as congenital kyphosis. Attempts to treat problems using traditional posterior spine surgeries often failed, leaving patients paraplegic. Using a procedure initially done in Hong Kong, surgeons from the University of Minnesota in 1966 became some of the first in the United States to access the thoracic spine from the anterior position, allowing for correction of deformities. This article highlights Minnesota surgeons' contributions to the development of anterior spine surgery.

Microwave Imaging of Breast Tumor Using Time-Domain UWB Circular-SAR Technique.

This paper explores the competency of the time domain ultra-wideband (UWB)-circular synthetic aperture radar (CSAR) to image the breast and detect tumors. The image reconstruction is performed using a time domain global back projection technique adapted to the circular trajectory data acquisition. This paper also proposes a sectional image reconstruction method to compensate for the group velocity changes in different layers of a multilayer medium. Experiments on an advanced breast phantom examines the suitability of this technique for breast tumor imaging. The advanced breast phantom is designed based on a MRI of a real patient, fabricated using 3D printing technology, and filled with liquids that emulate normal and cancerous tissues. The measurement results, compared with MRI imaging of the phantom, demonstrate the suitability of the UWB-CSAR method for breast tumor imaging. This method can be a tool for early diagnosis as well as for treatment monitoring during chemotherapy or radiotherapy.

Proposed Therapeutic Range of Treosulfan in Reduced Toxicity Pediatric Allogeneic Hematopoietic Stem Cell Transplant Conditioning: Results From a Prospective Trial.

Treosulfan is given off-label in pediatric allogeneic hematopoietic stem cell transplant. This study investigated treosulfan's pharmacokinetics (PKs), efficacy, and safety in a prospective trial. Pediatric patients (n = 87) receiving treosulfan-fludarabine conditioning were followed for at least 1 year posttransplant. PKs were described with a two-compartment model. During follow-up, 11 of 87 patients died and 12 of 87 patients had low engraftment (≤ 20% myeloid chimerism). For each increase in treosulfan area under the curve from zero to infinity (AUC(0-∞) ) of 1,000 mg hour/L the hazard ratio (95% confidence interval) for mortality increase was 1.46 (1.23-1.74), and the hazard ratio for low engraftment was 0.61 (0.36-1.04). A cumulative AUC(0-∞) of 4,800 mg hour/L maximized the probability of success (> 20% engraftment and no mortality) at 82%. Probability of success with AUC(0-∞) between 80% and 125% of this target were 78% and 79%. Measuring PK at the first dose and individualizing the third dose may be required in nonmalignant disease.

A concomitant posterior approach improves fusion rates but not overall reoperation rates in multilevel cervical fusion for spondylosis.

STUDY DESIGN: Retrospective comparative study of 2 approaches to multilevel fusion for cervical spondylosis in consecutive patients at a single institution. OBJECTIVE: To provide justification for a concomitant posterior approach in multilevel cervical fusion for spondylosis by demonstrating decreased pseudarthrosis and reoperation rates. SUMMARY OF BACKGROUND DATA: Among the factors that affect cervical rates is the number of levels, such that increasing the number of levels leads to lower fusion rates. Because of this, modifications have been sought to improve union in multilevel procedures. One option is an antero-posterior (AP) approach or circumferential arthrodesis. METHODS: Seventy-eight consecutive patients who underwent multilevel cervical fusion at a single institution and with minimum 2-year follow-up data were divided into an anterior-only group (anterior: n=55), and an AP group (AP: n=23). Union was assessed by surgical exploration, computerized tomography scan, and flexion-extension radiographs. The groups were compared in terms of pseudarthrosis rates and reoperation rates. RESULTS: Using chi(2) analysis, there was a significant difference in pseudarthrosis rates (anterior 38% vs. AP 0%; P<0.001), and reoperation rate for pseudarthrosis (anterior 22% vs. AP 0%; P=0.01). There were no differences in overall (anterior 36% vs. AP 30%; P=0.62) and early (anterior 15% vs. AP 26%; P=0.13) reoperation rates, but late reoperations were increased in the anterior group (24% vs. AP 4%; P=0.043). CONCLUSIONS: A concomitant posterior fusion significantly reduced the incidence of pseudarthrosis (0% vs. 38%) and pseudarthrosis-related reoperations (0% vs. 22%) compared with traditional anterior-only fusion. However, this did not translate to a difference in overall reoperation rates. The majority of reoperations in the AP group (86%) were performed within 6 months, whereas those in the anterior-only group (65%) were performed later, which was generally when a pseudarthrosis became evident.

Ultra-long-term follow-up of pediatric spinal deformity problems: 23 patients with a mean follow-up of 51 years.

BACKGROUND: The aim of this study was to analyze the true outcomes of a unique cohort of patients with spinal deformities who were treated as children and followed for 40 or more years. METHODS: Altogether, 23 patients were reviewed who had been originally treated in our community, whose original charts and radiographs were still available, and who had undergone recent evaluation. RESULTS: The diagnoses were congenital deformity in eight, adolescent idiopathic scoliosis in four, poliomyelitis in three, infantile idiopathic scoliosis in two, spondylolisthesis in two, and one each of tuberculosis and dwarfism. Sixteen had undergone fusion surgery. CONCLUSIONS: Early spine fusion for deformity produced far better results than delayed fusion. A solid fusion at the end of growth remained unchanged. Degenerative changes outside the fusion area were rare and seldom required further surgery. In summary, 23 patients with a mean follow-up of 51 years after treatment are presented. Early fusion was far superior to delayed or nonsurgical treatment.

Intrabone hematopoietic stem cell gene therapy for adult and pediatric patients affected by transfusion-dependent ß-thalassemia.

ß-thalassemia is caused by ß-globin gene mutations resulting in reduced (ß+) or absent (ß0) hemoglobin production. Patient life expectancy has recently increased, but the need for chronic transfusions in transfusion-dependent thalassemia (TDT) and iron chelation impairs quality of life1. Allogeneic hematopoietic stem cell (HSC) transplantation represents the curative treatment, with thalassemia-free survival exceeding 80%. However, it is available to a minority of patients and is associated with morbidity, rejection and graft-versus-host disease2. Gene therapy with autologous HSCs modified to express ß-globin represents a potential therapeutic option. We treated three adults and six children with ß0 or severe ß+ mutations in a phase 1/2 trial ( NCT02453477 ) with an intrabone administration of HSCs transduced with the lentiviral vector GLOBE. Rapid hematopoietic recovery with polyclonal multilineage engraftment of vector-marked cells was achieved, with a median of 37.5% (range 12.6-76.4%) in hematopoietic progenitors and a vector copy number per cell (VCN) of 0.58 (range 0.10-1.97) in erythroid precursors at 1 year, in absence of clonal dominance. Transfusion requirement was reduced in the adults. Three out of four evaluable pediatric participants discontinued transfusions after gene therapy and were transfusion independent at the last follow-up. Younger age and persistence of higher VCN in the repopulating hematopoietic cells are associated with better outcome.