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Background Readmissions following transcatheter aortic valve replacement (TAVR) are common but detailed analysis of cardiac and non-cardiac inpatient readmissions beyond thirty days to different levels of care are limited. Methods Our study population was 1,037 consecutive patients who underwent TAVR between 2011-2017 within a multi-hospital quaternary health system. A retrospective chart review was performed and readmissions were adjudicated and classified based on primary readmission diagnosis (cardiac versus noncardiac) and level of care [intensive care unit (ICU) admission vs. non-ICU admission]. Incidence, causes, and outcomes of readmissions to up to three years post procedure were evaluated. Results Of the 1,017 patients who survived their index hospitalization, there were readmissions due to noncardiac causes in 350 (34.4%) and cardiac causes in 208 (20.5%) during a mean 1.96 years of follow-up. The most common non-cardiac causes of readmission were sepsis/infection (14.3%), gastrointestinal (8.3%), and respiratory (4.8%), whereas heart failure (14.0%) and arrhythmias (4.6%) were the most common cardiac causes of readmission. A total of 191 (18.8%) patients were readmitted to the ICU and 372 patients (36.6%) were non-ICU readmissions. The risk of a noncardiac readmission was highest in the period immediately following TAVR (~4.5% per month) with an early high hazard phase that gradually declined over months. However, the risk of cardiac readmission remained stable at ~1% per month throughout. TAVR patients that were readmitted for any cause had markedly increased mortality; this was especially true for patients readmitted to an ICU. Conclusions In TAVR patients who survived their index hospitalization, non-cardiac readmissions were more prevalent than cardiac. The risk of readmission and subsequent mortality was highest immediately post-procedure and declined thereafter. Readmission to ICU portends the highest risk of subsequent death in this cohort. Patient baseline co-morbidities are an important consideration for TAVR patients and play a significant role in readmissions and outcomes.

Background Intervertebral disc degeneration contributes to low back pain. The avascular intervertebral disc consists of a central hypoxic nucleus pulpous (NP) surrounded by the more oxygenated annulus fibrosus (AF). Lactic acid, an abundant end-product of NP glycolysis, has long been viewed as a harmful waste that acidifies disc tissue and decreases cell viability and function. As lactic acid is readily converted into lactate in disc tissue, the objective of this study was to determine whether lactate could be used by AF cells as a carbon source rather than being removed from disc tissue as a waste byproduct. Methods Import and conversion of lactate to tricarboxylic acid (TCA) cycle intermediates and amino acids in rabbit AF cells were measured by heavy-isotope (13C-lactate) tracing experiments using mass spectrometry. Levels of protein expression of lactate converting enzymes, lactate importer and exporter in NP and AF tissues were quantified by Western blots. Effects of lactate on proteoglycan (35S-sulfate) and collagen (3H-proline) matrix protein synthesis and oxidative phosphorylation (Seahorse XFe96 Extracellular Flux Analyzer) in AF cells were assessed. Results Heavy-isotope tracing experiments revealed that AF cells imported and converted lactate into TCA cycle intermediates and amino acids using in vitro cell culture and in vivo models. Addition of exogenous lactate (4 mM) in culture media induced expression of the lactate importer MCT1 and increased oxygen consumption rate by 50%, mitochondrial ATP-linked respiration by 30%, and collagen synthesis by 50% in AF cell cultures grown under physiologic oxygen (2-5% O2) and glucose concentration (1-5 mM). AF tissue highly expresses MCT1, LDH-H, an enzyme that preferentially converts lactate to pyruvate, and PDH, an enzyme that converts pyruvate to acetyl-coA. In contrast, NP tissue highly expresses MCT4, a lactate exporter, and LDH-M, an enzyme that preferentially converts pyruvate to lactate. Conclusions These findings support disc lactate-dependent metabolic symbiosis in which lactate produced by the hypoxic, glycolytic NP cells is utilized by the more oxygenated AF cells via oxidative phosphorylation for energy and matrix production, thus shifting the current research paradigm of viewing disc lactate as a waste product to considering it as an important biofuel. These scientifically impactful results suggest novel therapeutic targets in disc metabolism and degeneration.

In this study, carbon/epoxy composites were manufactured by coating with a polyamide at different weight percentages (5 wt.%, 10 wt.%, 15 wt.%, and 20 wt.%) to improve their impact resistance and fracture toughness. The chemical reaction between the polyamide and epoxy resin were examined by fourier transform infrared spectroscopy, differential scanning calorimetry and X-ray photoelectron spectroscopy. The mechanical properties and fracture toughness of the carbon/epoxy composites were analyzed. The mechanical properties of the carbon/epoxy composites, such as transverse flexural tests, longitudinal flexural tests, and impact tests, were investigated. After the impact tests, an ultrasonic C-scan was performed to reveal the internal damage area. The interlaminar fracture toughness of the carbon/epoxy composites was measured using a mode I test. The critical energy release rates were increased by 77% compared to the virgin carbon/epoxy composites. The surface morphology of the fractured surface was observed. The toughening mechanism of the carbon/epoxy composites was suggested based on the confirmed experimental data.

Whether disc aging is influenced by factors beyond its local environment is an important unresolved question. Here we performed heterochronic parabiosis in mice to study the effects of circulating factors in young and old blood on age-associated intervertebral disc degeneration. Compared to young isochronic pairs (Y-Y), young mice paired with old mice (Y-O) showed significant increases in levels of disc MMP-13 and ADAMTS4, aggrecan fragmentation, and histologic tissue degeneration, but negligible changes in cellular senescence markers (p16INK4a, p21Cip1). Compared to old isochronic pairs (O-O), old mice paired with young mice (O-Y) exhibited a significant decrease in expression of cellular senescence markers (p16, p21, p53), but only marginal decreases in the levels of disc MMP-13 and ADAMTS4, aggrecan fragmentation, and histologic degeneration. Thus, exposing old mice to young blood circulation greatly suppressed disc cellular senescence, but only slightly decreased disc matrix imbalance and degeneration. Conversely, exposing young mice to old blood accelerated their disc matrix imbalance and tissue degeneration, with little effects on disc cellular senescence. Thus, non-cell autonomous effects of circulating factors on disc cellular senescence and matrix homeostasis are complex and suggest that disc matrix homeostasis is modulated by systemic factors and not solely through local disc cellular senescence.

Background: Current American College of Cardiology/American Heart Association guidelines recommend using the 10-year atherosclerotic cardiovascular disease (ASCVD) risk to guide statin therapy for primary prevention. Real-world data on adherence and consequences of nonadherence to the guidelines in primary are limited. We investigated the guideline-directed statin intensity (GDSI) and associated outcomes in a large health care system, stratified by ASCVD risk. Methods: Statin prescription in patients without coronary artery disease, peripheral vascular disease, or ischemic stroke were evaluated within a large health care network (2013–2017) using electronic medical health records. Patient categories constructed by the 10-year ASCVD risk were borderline (5%–7.4%), intermediate (7.5%–19.9%), or high (≥20%). The GDSI (before time of first event) was defined as none or any intensity for borderline, and at least moderate for intermediate and high-risk groups. Mean (±SD) time to start/change to GDSI from first interaction in health care and incident rates (per 1000 person-years) for each outcome were calculated. Cox regression models were used to calculate hazard ratios for incident ASCVD and mortality across risk categories stratified by statin utilization. Results: Among 282 298 patients (mean age ≈50 years), 29 134 (10.3%), 63 299 (22.4%), and 26 687 (9.5%) were categorized as borderline, intermediate, and high risk, respectively. Among intermediate and high-risk categories, 27 358 (43%) and 8300 (31%) patients did not receive any statin, respectively. Only 17 519 (65.6%) high-risk patients who were prescribed a statin received GDSI. The mean time to GDSI was ≈2 years among the intermediate and high-risk groups. At a median follow-up of 6 years, there was a graded increase in risk of ASCVD events in intermediate risk (hazard ratio=1.15 [1.07–1.24]) and high risk (hazard ratio=1.27 [1.17–1.37]) when comparing no statin use with GDSI therapy. Similarly, mortality risk among intermediate and high-risk groups was higher in no statin use versus GDSI. Conclusions: In a real-world primary prevention cohort, over one-third of statin-eligible patients were not prescribed statin therapy. Among those receiving a statin, mean time to GDSI was ≈2 years. The consequences of nonadherence to guidelines are illustrated by greater incident ASCVD and mortality events. Further research can develop and optimize health care system strategies for primary prevention.

Patients with atrial fibrillation (AF) commonly have impaired renal function. The safety and efficacy of direct oral anticoagulants (DOACs) in patients with chronic kidney disease (CKD) and end-stage renal disease has not been fully elucidated. This study evaluated and compared the safety outcomes of DOACs versus warfarin in patients with nonvalvular AF and concomitant CKD. Patients in our health system with AF prescribed oral anticoagulants during 2010 to 2017 were identified. All-cause mortality, bleeding and hemorrhagic, and ischemic stroke were evaluated based on degree of renal impairment and method of anticoagulation. There were 21,733 patients with a CHA2DS2-VASc score of ≥2 included in this analysis. Compared with warfarin, DOAC use in patients with impaired renal function was associated with lower risk of mortality with a hazard ratio (HR): 0.76 (95% confidence interval [CI] 0.70 to 0.84, p value 60, HR 0.74 (95% CI 0.68 to 0.81, p value 30 to 60, and HR 0.76 (95% CI 0.63 to 0.92, p value 60, HR 0.83 (95% CI 0.74 to 0.94, p value 0.003) in patients with eGFR >30 to 60, and HR 0.69 (95% CI 0.50 to 0.93, p value 0.017) in patients with eGFR ≤30 or on dialysis. In conclusion, in comparison to warfarin, DOACs appear to be safe and effective with a lower risk of all-cause mortality and lower bleeding across all levels of CKD.

Limited data exist for rates and causes of readmission beyond short-term follow-up for patients undergoing surgical and transcatheter aortic valve replacement (SAVR and TAVR) METHODS: Patients undergoing isolated SAVR and TAVR between 2011 and 2017 at our institution were included in this study. The primary outcome was 5-year hospital readmission. The readmission cohort was identified from index readmission. Multivariable logistic regression analysis was used to evaluate the risk-adjusted impact of TAVR vs SAVR on outcomes.A total of 2379 patients were included: 1034 TAVR (43.5%) and 1345 SAVR (56.5%). Patients undergoing TAVR were on average older (81.8 ± 7.8 years vs 69.1 ± 11.85 years, P.0001) and had more comorbidities than SAVR patients as represented by a greater Society of Thoracic Surgeons Predicted Risk of Mortality (7.96% ± 4.71% vs 2.73% ± 2.93%, P.0001). Operative mortality was higher in the TAVR cohort (3.19% vs 1.12%, P.004) and remained high at 5 years despite risk adjustment. Significantly more cardiac readmissions were found at 5-year follow-up in the TAVR group (73.3% vs 60.0%, P.0001). Heart failure was the most common cause of cardiac readmission in the TAVR cohort (58.7% vs 42.1%, P = .0001). No difference was found in overall readmission risk at 30 days (hazard ratio [HR] 1.23, 95% confidence interval [CI]: 0.94 to 1.61, P = .12), 1 year (HR 0.93, 95% CI: 0.77 to 1.16, P = .52), and 5 years (HR 0.99, 95% CI: 0.83 to 1.18, P = .89).There is a disproportionately high rate of long-term hospital readmissions for cardiac causes, including heart failure, in patients who underwent TAVR. These data may support aggressive medical management of patients with careful follow-up in patients undergoing TAVR.

Proto‐Araceae, the earliest diverged lineage within the family Araceae, includes two subfamilies, Gymnostachydoideae (one species) and Orontioideae (eight species). Based on an extensive sampling (a total of 198 accessions) of six chloroplast non‐coding regions (5799 aligned sites), we assessed phylogenetic relationships among the genera and species within subfamily Orontioideae and estimated the timing of intercontinental disjunct events in the Northern Hemisphere. Overall phylogenetic relationships among the genera were consistent with results from previous studies, but several new important findings were discovered, primarily within Symplocarpus Salisb. ex W. P. C. Barton. First, two major lineages within Symplocarpus were identified: one lineage included S. foetidus (L.) Salisb. ex W. Barton, S. nabekuraensis Otsuka & K. Inoue, and S. renifolius Schott ex Tzvelev (Japan), whereas the other included S. nipponicus Makino, S. egorovii N. S. Pavlova & V. A. Nechaev, and S. renifolius (Korea). Symplocarpus renifolius in Japan was tetraploid and closely related to the tetraploid S. foetidus in eastern North America. Populations of S. renifolius in Korea were confirmed to be diploid (2n = 30) and shared the most recent common ancestor with the other diploid species, S. nipponicus. Second, two recently described species, S. nabekuraensis and S. egorovii, were deeply embedded within S. renifolius in Japan and Korea, respectively, and their distinct taxonomic status requires further assessment. Finally, two intercontinental disjunction events in the subfamily, one in Lysichiton Schott between eastern Asia and western North America and the other in Symplocarpus between eastern Asia and eastern North America, were estimated to be between 4.5 and 1.4 million years ago (Pliocene and Pleistocene) and between 1.9 and 0.5 million years ago (Pleistocene), respectively.

Introduction Ubiquitously found in all life forms, inorganic polyphosphates (polyP) are linear polymers of repeated orthophosphate units. Present in intervertebral disc tissue, polyP was previously shown to increase extracellular matrix production in nucleus pulposus (NP) cells. However, the effects of polyP on human annulus fibrosus (hAF) cell metabolism is not known. Methods and Results Here, hAF cells cultured in the presence of 0.5 to 1 mM polyP, chain length 22 (polyP‐22), showed an increase in glycosaminoglycan content, proteoglycan and collagen synthesis, and aggrecan and collagen type 1 gene expression. Gene expression level of matrix metalloproteinases 1 was reduced while matrix metalloproteinases 3 level was increased in hAF cells treated with 1 mM polyP. Adenosine triphosphate (ATP) synthesis was also significantly increased in hAF cell culture 72 hours after the exposure to 1 mM polyP‐22. Conclusions PolyP thus has both anabolic and bioenergetic effects in AF cells, similar to that observed in NP cells. Together, these results suggest polyP as a potential energy source and a metabolic regulator of disc cells., The current study investigates the effect of inorganic polyphosphates (polyPs) on human annulus fibrosus (AF) cell biology. This is a first study of its kind to investigate the effect of polyPs on human AF cells. polyPs, rich in polyanhydride bonds and known donors of phosphate molecule for ATP synthesis, showed increase in matrix production and ATP generation in human AF cells and overall promoted anabolism.

Approximately 10% of agricultural land is subject to periodic flooding, which reduces the growth, survivorship, and yield of most crops, reinforcing the need to understand and enhance flooding resistance in our crops. Here, we generated RNA-Seq data from leaf and root tissue of domesticated sunflower to explore differences in gene expression and alternative splicing (AS) between a resistant and susceptible cultivar under both flooding and control conditions and at three time points. Using a combination of mixed model and gene co-expression analyses, we were able to separate general responses of sunflower to flooding stress from those that contribute to the greater tolerance of the resistant line. Both cultivars responded to flooding stress by upregulating expression levels of known submergence responsive genes, such as alcohol dehydrogenases, and slowing metabolism-related activities. Differential AS reinforced expression differences, with reduced AS frequencies typically observed for genes with upregulated expression. Significant differences were found between the genotypes, including earlier and stronger upregulation of the alcohol fermentation pathway and a more rapid return to pre-flooding gene expression levels in the resistant genotype. Our results show how changes in the timing of gene expression following both the induction of flooding and release from flooding stress contribute to increased flooding tolerance.

Polyploidy has been a prevalent process during plant evolution and it has made a major impact on the structure and evolution of plant genomes. Many important crop plants are polyploid. There is considerable interest in expression patterns of duplicated genes in polyploids. Alternative splicing (AS) is a fundamental aspect of gene expression that produces multiple final transcript types from a single type of mRNAs. The effects of abiotic stress conditions on AS in polyploids has received little attention. We conducted a global transcriptome analysis of Brassica napus, an allotetraploid derived from B. rapa (AT) and B. oleracea (CT), by RNA‐Seq of plants subjected to cold, heat, and drought stress treatments. Analyses of 27,360 pairs of duplicated genes revealed overall AT subgenome biases in gene expression and CT subgenome biases in the extent of alternative splicing under all three stress treatments. More genes increased in expression than decreased in response to the stresses. Negative correlations were found between expression levels and AS frequency for each type of AS. Cold stress produced the greatest changes in gene expression and AS. Cold‐induced AS changes were more likely to be shared with those generated by drought than by heat stress. We used homeologs of FLC and CCA1 as case studies to show the dynamics of how duplicates in a polyploid respond to cold stress. Our results suggest that divergence in gene expression and AS patterns between duplicated genes may increase the flexibility of polyploids when responding to abiotic stressors.

Surgical risk stratified outcomes after contemporary revascularization strategies have not been well described. We report these outcomes in patients undergoing percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) for multivessel coronary disease.A total of 5836 patients with multivessel disease who underwent CABG (n = 4420) or PCI (n = 1416) were included in this retrospective observational analysis. Data were stratified based on The Society of Thoracic Surgeons risk score. A score less than 4% was considered low risk and a score greater than or equal to 4% was considered intermediate-high risk. Outcomes included mortality, inpatient readmissions, and repeat revascularizations.In the CABG population, 3863 (87.3%) were low risk and 557 (12.6%) were intermediate-high risk. The 5-year mortality for the low-risk cohort was 10.9% (95% confidence interval [CI], 9.83%-12.05%), and for the intermediate-high-risk cohort it was 40.1% (95% CI, 35.76%-44.54%). Among those undergoing PCI, 1163 (82.1%) were low risk, while 249 (17.6%) were intermediate-high risk. The 5-year mortality for the low-risk cohort was 21.6% (95% CI, 19.10%-24.26%), and for the intermediate-high-risk cohort it was 61.8% (95% CI, 54.72%-68.70%).This study reports outcomes stratified by surgical risk after PCI or CABG in patients with multivessel coronary disease. These data can help guide the revascularization strategy choice for individual patients.

Objectives The use of monitored anesthesia care (MAC) for transcatheter aortic valve replacement (TAVR) is gaining favor in the United States, although general anesthesia (GA) continues to be common for these procedures. Open surgical cutdown for transfemoral TAVR has been a relative contraindication for TAVR with MAC at most centers. The objective of this study was to review the authors’ results of transfemoral TAVR performed in patients with open surgical cutdown with the use of MAC. Design Retrospective study design from a prospectively recorded database. Setting Tertiary academic (teaching) hospital. Participants Two hundred eighty-two patients undergoing transfemoral TAVR with open surgical cutdown under MAC from 2015 to 2017. Interventions Transfemoral TAVR under MAC with surgical cutdown for femoral vascular access. Measurements and Main Results The study cohort consisted of 282 patients with severe aortic stenosis (mean area 0.65 [± 0.16] cm2, mean gradient of 48.9 [±13.3] mmHg, and mean age of 82.7 [± 7.31] years). Eleven (3.9%) patients required conversion to GA. First postoperative pain score (0-10) was 2.9 and highest postoperative pain score was 4.6. Major and minor vascular complications occurred in 2 (0.7%) and 6 (2.1%) patients, respectively. Twenty-nine (10.3%) patients were readmitted within 30 days, and 6 (2.1%) patients had in-hospital mortality. Conclusions Open surgical cutdown for transfemoral TAVR can be performed safely using MAC and ilioinguinal block with low rates of conversion to general anesthesia and acceptable postoperative outcomes and pain scores.

We aimed to evaluate the association between pulmonary hypertension (PH) hemodynamic classification and all-cause mortality in patients with symptomatic severe aortic stenosis (AS) undergoing transcatheter aortic valve implantation (TAVI). PH is common and associated with post-TAVI outcomes in patients with severe AS. Although PH in these patients is primarily driven by elevated left-sided pressures (postcapillary PH), some patients develop increased pulmonary vascular resistance (PVR) configuring the combined pre- and postcapillary PH (CpcPH). We analyzed severe AS patients with mean pulmonary artery pressure (mPAP) measured by right heart catheterization (RHC) before TAVI between 2011 and 2017. PH hemodynamic classification was defined as: No PH (mPAP25 mm Hg); precapillary PH (mPAP ≥ 25 mm Hg, pulmonary capillary wedge pressure (PCWP) ≤15 mm Hg); isolated postcapillary PH (IpcPH; mPAP ≥ 25 mm Hg, PCWP15 mm Hg, PVR ≤ 3 Wood units (WU); CpcPH (mPAP ≥ 25 mm Hg, PCWP15 mm Hg, PVR3 WU). Kaplan-Meier and Cox regression analyses were used to test the association of PH hemodynamic classification with post-TAVI all-cause mortality. We examined 561 patients (mean age 82 ± 8 years, 51% men, mean LVEF 54 ± 14%). The prevalence of no PH was 201 (36%); precapillary PH, 59 (10%); IpcPH, 189 (34%); and CpcPH, 112 (20%). During a median follow-up of 30 months, 240 all-cause deaths occurred. Patients with CpcPH had higher mortality than those with no-PH even after adjustment for baseline characteristics (Hazard ratio 1.56, 95% confidence interval 1.06 to 2.29, p = 0.025). There was no survival difference among patients with non-PH, precapillary PH and IpcPH. In conclusion, for patients with symptomatic severe AS treated with TAVI, CcpPH is independently associated with long-term all-cause mortality despite successful TAVI.

Suppression of the insulin‐like growth factor‐1 (IGF‐1) signaling pathway reduces age‐related disorders and increases lifespan across species, making the IGF‐1 pathway a key regulator of aging. Previous in vitro intervertebral disc cell studies have reported the pro‐anabolic effect of exogenously adding IGF‐1 on matrix production. However, the overall effects of suppressing IGF‐1 signaling on age‐related intervertebral disc degeneration (IDD) is not known. Here, the effects of suppressing IGF‐1 signaling on age‐related IDD in vivo were examined using PAPPA −/− mice. These are animals with targeted deletion of pregnancy‐associated plasma protein A (PAPPA), the major protease that cleaves inhibitory IGF binding proteins that control bioavailability of IGF‐1 for cell signaling. Compared to age‐matched wild‐type (Wt) littermates, reduced levels of matrix proteoglycan (PG) and aggrecan were seen in discs of 23‐month old PAPPA −/− mice. Decreased aggrecanolysis and expression of two key catabolic markers, matrix metalloproteinase‐3 and a disintegrin and metalloproteinase with thrombospondin motifs‐4, were also observed in discs of old PAPPA −/− mice compared to Wt littermates. Suppressing IGF‐1 signaling has been implicated to shift cellular metabolism toward maintenance rather than growth and decreasing cellular senescence. Along this line, discs of old PAPPA −/− mice also exhibited lower cellular senescence, assessed by p53 and lamin B1 markers. Collectively, the data reveal complex regulation of disc matrix homeostasis by PAPPA/IGF‐1 signaling during chronologic aging, that is, reduced IGF‐1 bioavailability confers the benefit of decreasing disc cellular senescence and matrix catabolism but also the disadvantage of decreasing disc PG matrix anabolism. This pathway requires further mechanistic elucidation before IGF‐1 could be considered as a therapeutic growth factor for treating IDD.

Background The CoreValve U.S. Pivotal High Risk Trial was the first randomized trial to show superior 1-year mortality of transcatheter aortic valve replacement (TAVR) compared with surgical aortic valve replacement (SAVR) among high operative mortality–risk patients. Objectives The authors sought to compare TAVR to SAVR for mid-term 5-year outcomes of safety, performance, and durability. Methods Surgical high-risk patients were randomized (1:1) to TAVR with the self-expanding bioprosthesis or SAVR. VARC-1 (Valve Academic Research Consortium I) definitions were applied. Severe hemodynamic structural valve deterioration was defined as a mean gradient ≥40 mm Hg or a change in gradient ≥20 mm Hg or new severe aortic regurgitation. Five-year follow-up was planned. Results A total of 797 patients were randomized at 45 U.S. centers, of whom 750 underwent an attempted implant (TAVR = 391, SAVR = 359). The overall mean age was 83 years, and the STS score was 7.4%. All-cause mortality rates at 5 years were 55.3% for TAVR and 55.4% for SAVR. Subgroup analysis showed no differences in mortality. Major stroke rates were 12.3% for TAVR and 13.2% for SAVR. Mean aortic valve gradients were 7.1 ± 3.6 mm Hg for TAVR and 10.9 ± 5.7 mm Hg for SAVR. No clinically significant valve thrombosis was observed. Freedom from severe SVD was 99.2% for TAVR and 98.3% for SAVR (p = 0.32), and freedom from valve reintervention was 97.0% for TAVR and 98.9% for SAVR (p = 0.04). A permanent pacemaker was implanted in 33.0% of TAVR and 19.8% of SAVR patients at 5 years. Conclusions This study shows similar mid-term survival and stroke rates in high-risk patients following TAVR or SAVR. Severe structural valve deterioration and valve reinterventions were uncommon. (Safety and Efficacy Study of the Medtronic CoreValve® System in the Treatment of Symptomatic Severe Aortic Stenosis in High Risk and Very High Risk Subjects Who Need Aortic Valve Replacement; NCT01240902 )

Mobile radiation sensing techniques for surge deployment and wide area search are important for nuclear security applications. Radiation sensors were developed for the use with robotic platforms of unmanned aerial systems (UAS). Ambient temperature neutron and gamma CLYC sensor and high resolution CZT gamma sensor were integrated into the UAS as plug-and-play interchangeable components allowing easy attachment to a robot in field conditions. The time and position data were added via Robot Operating System to measured intensities of photon peaks and neutron rates enabling the input for the UAS flight control. The contour mapping of a radiation area by multiple UAS was simulated.

OBJECTIVES Despite the established efficacy of transcatheter aortic valve replacement for aortic valve replacement, vascular complications remain a major cause of procedural morbidity and mortality. In this study, we evaluate the use of femoral artery cut down with conscious sedation and report outcomes and complications associated with this approach. METHODS Our study included 282 patients undergoing transcatheter aortic valve replacement with conscious sedation and surgical cut down for femoral access between 2015 and 2017. Data were prospectively recorded in the local institutional database and were retrospectively accessed. Descriptive statistics are presented, and a Kaplan-Meier time-to-event plot was used to estimate 1-year survival. RESULTS The mean age of the patients was 82.7 ± 7.31 years and consisted of 146 (52%) women. Echocardiographic data demonstrated a severe aortic stenosis with a mean area of 0.65 ± 0.16 cm2 and a mean gradient of 48.9 ± 13.3 mmHg. STS-PROM for the cohort was 7.2%, representing an intermediate risk group. Six (2.2%) patients died within 30 days after transcatheter aortic valve replacement. Major vascular complications occurred in 2 (0.7%) patients and minor vascular complications occurred in 6 (2.2%) patients in our cohort. Wound complications were observed in 2 (0.7%) patients. CONCLUSIONS We demonstrate that the use of conscious sedation and surgical cut down for femoral arterial access resulted in a major vascular complication rate of less than 1% and low in-hospital mortality rates without any significant increase in wound complications.

Diagnosing dysfunctional atlantoaxial motion is challenging given limitations of current diagnostic imaging techniques. Three-dimensional imaging during upright functional motion may be useful in identifying dynamic instability not apparent on static imaging. Abnormal atlantoaxial motion has been linked to numerous pathologies including whiplash, cervicogenic headaches, C2 fractures, and rheumatoid arthritis. However, normal C1/C2 rotational kinematics under dynamic physiologic loading have not been previously reported owing to imaging difficulties. The objective of this study was to determine dynamic three-dimensional in vivo C1/C2 kinematics during upright axial rotation. Twenty young healthy adults performed full head rotation while seated within a biplane X-ray system while radiographs were collected at 30 images per second. Six degree-of-freedom kinematics were determined for C1 and C2 via a validated volumetric model-based tracking process. The maximum global head rotation (to one side) was 73.6±8.3°, whereas maximum C1 rotation relative to C2 was 36.8±6.7°. The relationship between C1/C2 rotation and head rotation was linear through midrange motion (±20° head rotation from neutral) in a nearly 1:1 ratio. Coupled rotation between C1 and C2 included 4.5±3.1° of flexion and 6.4±8.2° of extension, and 9.8±3.8° of contralateral bending. Translational motion of C1 relative to C2 was 7.8±1.5mm ipsilaterally, 2.2±1.2mm inferiorly, and 3.3±1.0mm posteriorly. We believe this is the first study describing 3D dynamic atlantoaxial kinematics under true physiologic conditions in healthy subjects. C1/C2 rotation accounts for approximately half of total head axial rotation. Additionally, C1 undergoes coupled flexion/extension and contralateral bending, in addition to inferior, lateral and posterior translation.

Objective Low back pain is frequently treated with nonsteroidal anti-inflammatory drugs (NSAIDs), but little is known about intervertebral disc metabolism of the prostaglandins that are diminished by these drugs. Hence, this study aimed at delineating prostaglandin actions in cytokine activated disc cells by comparing the response of nucleus pulposus (NP) cells to the pro-inflammatory cytokine interleukin (IL)-1β with and without cyclooxygenase 2 (COX-2) inhibition. Methods NP cells cultured in alginate beads were activated with IL-1β ± the COX-2 inhibitor Sc-58125. Media harvested from cultured cells were analyzed for prostaglandin E2 (PGE2), prostaglandin F2 alpha (PGF2α), IL-6, and matrix metalloproteinase (MMP)-3 by enzymelinked immunosorbent assay and nitric oxide by Griess Reaction. Gene expression along with proteoglycan, collagen, and total protein synthesis were also measured. Results IL-1β increased culture media PGE2 and PGF2α, but decreased proteoglycan and collagen syntheses as well as mRNA expression of the matrix genes aggrecan, versican, collagen I, and collagen II. COX-2 inhibition partially rescued proteoglycan and collagen syntheses and collagen I mRNA, but decreased collagen II mRNA IL-1β activated NP cells. COX-2 inhibition initially enhanced and subsequently reduced IL-1β induced inducible nitric oxide synthase, without altering medium nitrite. IL-1β induction of MMP-3 mRNA was increased by COX-2 inhibition at 24 and 48 hours. Conclusion COX-2 inhibition alters the response of NP cells to IL-1β, suggesting IL-1β action on disc cells is mediated at least in part through COX-2 and its prostaglandins. COX-2 inhibition produces minimal effects on several key catabolic mediators, with the exception of MMP-3. Blocking COX-2 might be beneficial for maintaining disc matrix since it provides an overall rescue of IL-1 induced loss of matrix protein synthesis.

OBJECTIVES This study compared contemporary outcomes following surgical versus percutaneous coronary revascularization for multivessel coronary artery disease (MVCAD) in patients with chronic kidney disease. METHODS Patients with MVCAD and a reduced glomerular filtration rate ( RESULTS A total of 1853 patients were included in the study (1269 CABG, 584 PCI). CABG was associated with greater 5-year freedom from MACCE (70.1% vs 47.3%, P CONCLUSIONS CABG is associated with a lower MACCE rate than that of PCI in patients with MVCAD and chronic kidney disease. Multidisciplinary discussions regarding the optimal revascularization strategy are important in MVCAD, particularly in more complex scenarios such as chronic kidney disease.

IMPORTANCE: Severe aortic stenosis causes pressure overload of the left ventricle, resulting in progressive cardiac dysfunction that can extend beyond the left ventricle. A staging system for aortic stenosis has been recently proposed that quantifies the extent of structural and functional cardiac changes in aortic stenosis. OBJECTIVES: To confirm the reproducibility of a proposed staging system and expand the study findings by performing a survival analysis and to evaluate the association of aortic stenosis staging with both cardiac and noncardiac post–transcatheter aortic valve replacement (TAVR) readmissions. DESIGN, SETTING, AND PARTICIPANTS: A cohort analysis was conducted involving patients with severe aortic stenosis who underwent TAVR at the University of Pittsburgh Medical Center between July 1, 2011, and January 31, 2017. Patients who had undergone TAVR for valve-in-valve procedures and had an incomplete or unavailable baseline echocardiogram study for review were excluded. Clinical, laboratorial, and procedural data were collected from the Society of Thoracic Surgeons database and augmented by electronic medical record review. EXPOSURES: The aortic stenosis staging system is based on echocardiographic markers of abnormal cardiac function. The stages are as follows: stage 1 (left ventricle changes − increased left ventricular mass index; early mitral inflow to early diastolic mitral annulus velocity (E/e′) >14; and left ventricular ejection fraction 34 mL/m(2); moderate to severe mitral regurgitation; and atrial fibrillation), stage 3 (pulmonary artery or tricuspid changes − pulmonary artery systolic pressure ≥60 mm Hg; moderate to severe tricuspid regurgitation), and stage 4 (right ventricle changes − moderate to severe right ventricle dysfunction). MAIN OUTCOMES AND MEASURES: Primary outcome was post-TAVR all-cause mortality. Secondary outcomes were composite outcomes of all-cause mortality and post-TAVR all-cause and cardiac-cause readmissions. RESULTS: A total of 689 consecutive patients (351 [50.9%] were male, with a mean [SD] age of 82.4 [7.6] years) were included. The prevalence of stage 1 was 13%; stage 2, 62%; stage 3, 21%; and stage 4, 4%. Patients with higher staging had a greater burden of comorbidities as captured by the Society of Thoracic Surgeons Predicted Risk of Mortality (STS-PROM). Despite adjustment for STS-PROM, a graded association was found between aortic stenosis staging and all-cause mortality (hazard ratio [HR] stage 2 vs stage 1: 1.37 [95% CI, 0.81-2.31; P = .25]; stage 3 vs stage 1: 2.24 [95% CI, 1.28-3.92; P = .005]; and stage 4 vs stage 1: 2.83 [95% CI, 1.39-5.76; P = .004]). Stage 3 patients had higher post-TAVR readmission rates for both cardiac (HR, 1.84; 95% CI, 1.13-3.00; P = .01) and noncardiac causes. CONCLUSIONS AND RELEVANCE: Aortic stenosis staging appears to show a strong graded association between the extent of cardiac changes and post-TAVR all-cause mortality; such staging may improve patient care, risk stratification, assessment of prognosis, and shared decision making for patients undergoing TAVR.

BACKGROUND Although transcatheter aortic-valve replacement (TAVR) is an accepted alternative to surgery in patients with severe aortic stenosis who are at high surgical risk, less is known about comparative outcomes among patients with aortic stenosis who are at intermediate surgical risk. METHODS We evaluated the clinical outcomes in intermediate-risk patients with severe, symptomatic aortic stenosis in a randomized trial comparing TAVR (performed with the use of a self-expanding prosthesis) with surgical aortic-valve replacement. The primary end point was a composite of death from any cause or disabling stroke at 24 months in patients undergoing attempted aortic-valve replacement. We used Bayesian analytical methods (with a margin of 0.07) to evaluate the noninferiority of TAVR as compared with surgical valve replacement. RESULTS A total of 1746 patients underwent randomization at 87 centers. Of these patients, 1660 underwent an attempted TAVR or surgical procedure. The mean (±SD) age of the patients was 79.8±6.2 years, and all were at intermediate risk for surgery (Society of Thoracic Surgeons Predicted Risk of Mortality, 4.5±1.6%). At 24 months, the estimated incidence of the primary end point was 12.6% in the TAVR group and 14.0% in the surgery group (95% credible interval [Bayesian analysis] for difference, -5.2 to 2.3%; posterior probability of noninferiority, >0.999). Surgery was associated with higher rates of acute kidney injury, atrial fibrillation, and transfusion requirements, whereas TAVR had higher rates of residual aortic regurgitation and need for pacemaker implantation. TAVR resulted in lower mean gradients and larger aortic-valve areas than surgery. Structural valve deterioration at 24 months did not occur in either group. CONCLUSIONS TAVR was a noninferior alternative to surgery in patients with severe aortic stenosis at intermediate surgical risk, with a different pattern of adverse events associated with each procedure. (Funded by Medtronic; SURTAVI ClinicalTrials.gov number, NCT01586910 .).

Background Dual antiplatelet therapy is recommended for patients with acute coronary syndrome (ACS) that undergo percutaneous coronary intervention (PCI). However, the effect of switching P2Y12 inhibitors between the loading dose and therapy after discharge is not well described. Methods This post-hoc analysis of a prospectively collected registry included 3219 consecutive ACS patients who underwent PCI. Patients were categorized into four groups: clopidogrel at load and discharge (C–C), loading dose of clopidogrel and discharged on prasugrel/ticagrelor (C–PT), loading dose of prasugrel/ticagrelor and discharged on clopidogrel (PT–C), and prasugrel/ticagrelor at load and discharge (PT–PT). Results While 77.6% of patients received the C–C treatment regimen and 13.6% received the PT–PT strategy, the strategy of P2Y12 switching was fairly common with 6.2% in the PT–C group and 2.6% in the C–PT group. While C–C was the most common treatment regimen, PT–C and PT–PT were more commonly used in STEMI patients than in NSTEMI or unstable angina patients. A significantly lower unadjusted incidence of the composite outcome (death, MI, and repeat revascularization) was appreciated in both the PT–C (1.0%) and PT–PT (2.3%) groups than the C–C group (4.0%). Propensity-score matched analysis still showed significantly reduced risk (HR=0.22, 95% CI 0.05–0.93, p=0.04) in the PT–C group vs. a matched group of C–C controls. Conclusions The strategy of utilizing a newer P2Y12 inhibitor and then switching to clopidogrel in ACS patients following PCI is used with some frequency in routine clinical practice and further studies should evaluate the safety and efficacy of such a strategy.

In patients with severe aortic stenosis at increased risk for surgery, self-expanding transcatheter aortic valve replacement (TAVR) is associated with improved 2-year survival compared with surgery.This study sought to determine whether this clinical benefit was sustained over time.Patients with severe aortic stenosis deemed at increased risk for surgery by a multidisciplinary heart team were randomized 1:1 to TAVR or open surgical valve replacement (SAVR). Three-year clinical and echocardiographic outcomes were obtained in those patients with an attempted procedure.A total of 797 patients underwent randomization at 45 U.S. centers; 750 patients underwent an attempted procedure. Three-year all-cause mortality or stroke was significantly lower in TAVR patients (37.3% vs. 46.7% in SAVR; p = 0.006). Adverse clinical outcome components were also reduced in TAVR patients compared with SAVR patients, including all-cause mortality (32.9% vs. 39.1%, respectively; p = 0.068), all stroke (12.6% vs. 19.0%, respectively; p = 0.034), and major adverse cardiovascular or cerebrovascular events (40.2% vs. 47.9%, respectively; p = 0.025). At 3 years aortic valve hemodynamics were better with TAVR patients (mean aortic valve gradient 7.62 ± 3.57 mm Hg vs. 11.40 ± 6.81 mm Hg in SAVR; p0.001), although moderate or severe residual aortic regurgitation was higher in TAVR patients (6.8% vs. 0.0% in SAVR; p0.001). There was no clinical evidence of valve thrombosis in either group.Patients with severe aortic stenosis at increased risk for surgery had improved 3-year clinical outcomes after TAVR compared with surgery. Aortic valve hemodynamics were more favorable in TAVR patients without differences in structural valve deterioration. (Safety and Efficacy Study of the Medtronic CoreValve(®) System in the Treatment of Symptomatic Severe Aortic Stenosis in High Risk and Very High Risk Subjects Who Need Aortic Valve Replacement; NCT01240902).

Author(s): Patil, Prashanti; Dong, Qing; Wang, Dong; Chang, Jianhui; Wiley, Christopher; Demaria, Marco; Lee, Joon; Kang, James; Niedernhofer, Laura J; Robbins, Paul D; Sowa, Gwendolyn; Campisi, Judith; Zhou, Daohong; Vo, Nam | Abstract: RationaleAge-related changes in the intervertebral discs are the predominant contributors to back pain, a common physical and functional impairment experienced by older persons. Cellular senescence, a process wherein cells undergo growth arrest and chronically secrete numerous inflammatory molecules and proteases, has been reported to cause decline in the health and function of multiple tissues with age. Although senescent cells have been reported to increase in intervertebral degeneration (IDD), it is not known whether they are causative in age-related IDD.ObjectiveThe study aimed to elucidate whether a causal relationship exists between cellular senescence and age-related IDD.Methods and resultsTo examine the impact of senescent cells on age-associated IDD, we used p16-3MR transgenic mice, which enables the selective removal of p16Ink4a -positive senescent cells by the drug ganciclovir. Disc cellularity, aggrecan content and fragmentation alongside expression of inflammatory cytokine (IL-6) and matrix proteases (ADAMTS4 and MMP13) in discs of p16-3MR mice treated with GCV and untreated controls were assessed. In aged mice, reducing the per cent of senescent cells decreased disc aggrecan proteolytic degradation and increased overall proteoglycan matrix content along with improved histological disc features. Additionally, reduction of senescent cells lowered the levels of MMP13, which is purported to promote disc degenerative changes during aging.ConclusionsThe findings of this study suggest that systemic reduction in the number of senescent cells ameliorates multiple age-associated changes within the disc tissue. Cellular senescence could therefore serve as a therapeutic target to restore the health of disc tissue that deteriorates with age.

International audience; Domesticated plants and animals often display dramatic responses to selection, but the origins of the genetic diversity underlying these responses remain poorly understood. Despite domestication and improvement bottlenecks, the cultivated sunflower remains highly variable genetically, possibly due to hybridization with wild relatives. To characterize genetic diversity in the sunflower and to quantify contributions from wild relatives, we sequenced 287 cultivated lines, 17 Native American landraces and 189 wild accessions representing 11 compatible wild species. Cultivar sequences failing to map to the sunflower reference were assembled de novo for each genotype to determine the gene repertoire, or 'pan-genome', of the cultivated sunflower. Assembled genes were then compared to the wild species to estimate origins. Results indicate that the cultivated sunflower pan-genome comprises 61,205 genes, of which 27% vary across genotypes. Approximately 10% of the cultivated sunflower pan-genome is derived through introgression from wild sunflower species, and 1.5% of genes originated solely through introgression. Gene ontology functional analyses further indicate that genes associated with biotic resistance are over-represented among introgressed regions, an observation consistent with breeding records. Analyses of allelic variation associated with downy mildew resistance provide an example in which such introgressions have contributed to resistance to a globally challenging disease.

Remote sensing of radiological and nuclear materials is important for safety and security. Gamma-ray and neutron detectors can be deployed in the field using robotic platforms. Unmanned aerial systems (UAS) and ground vehicles (UGV) allow remote radiation sensing operations in hard to reach hazardous areas where the level of contamination is unknown while keeping users away from the risk of exposure. In order to achieve this, radiation sensors must be integrated with robotic platforms. A CZT semiconductor detector and a CLYC scintillation detector were integrated with a multicopter aerial platform and a ground vehicle. The Robot Operating System (ROS) was used for the detector’s data fusion. Functions were developed within ROS to perform automated gamma spectrum analysis and neutron/gamma discrimination. Each measurement was supplied with real-time kinematic GPS data and a timestamp enabling analysis of the radiation flux in temporal and spatial coordinates. Moreover, a plug-and-play interface was designed for both detectors to enable their user-friendly application in field conditions.

Given the rising risk of extreme weather caused by climate change, enhancement of abiotic stress resistance in crops is increasingly urgent. But will the development of stress-resistant cultivars come at the cost of yield under ideal conditions? We hypothesize that this need not be inevitable, because resistance alleles with minimal pleiotropic costs may evade artificial selection and be retained in crop germplasm. Genome-wide association (GWA) analyses for variation in plant performance and flooding response were conducted in cultivated sunflower, a globally important oilseed. We observed broad variation in flooding responses among genotypes. Flooding resistance was not strongly correlated with performance in control conditions, suggesting no inherent trade-offs. Consistent with this finding, we identified a subset of loci conferring flooding resistance, but lacking antagonistic effects on growth. Genetic diversity loss at candidate genes underlying these loci was significantly less than for other resistance genes during cultivated sunflower evolution. Despite bottlenecks associated with domestication and improvement, low-cost resistance alleles remain within the cultivated sunflower gene pool. Thus, development of cultivars that are both flooding-tolerant and highly productive should be straightforward. Results further indicate that estimates of pleiotropic costs from GWA analyses explain, in part, patterns of diversity loss in crop genomes.

Age is a major risk factor for multiple disease pathologies, including chronic back pain, which stems from age-related degenerative changes to intervertebral disc tissue. Growing evidence suggests that the change in phenotype of disc cells to a senescent phenotype may be one of the major driving forces of age-associated disc degeneration. This review discusses the known stressors that promote development of senescence in disc tissue and the underlying molecular mechanisms disc cells adopt to enable their transition to a senescent phenotype. Increased number of senescent cells has been observed with advancing age and degeneration in disc tissue. Additionally, in vitro studies have confirmed the catabolic nature of stress-induced senescent disc cells. Several factors have been shown to establish senescence via multiple different underlying mechanisms, including the NF-κB, Wnt/B-Catenin, and SIRT1 pathways. Cellular senescence can serve as a therapeutic target to combat age-associated disc degeneration. However, whether the different stressors utilizing different signaling networks establish different kinds of senescent types in disc cells is currently unknown and warrants further investigation.

Cellular senescence is a phenotype characterized by irreversible growth arrest, chronic elevated secretion of proinflammatory cytokines and matrix proteases, a phenomenon known as senescence-associated secretory phenotype (SASP). Biomarkers of cellular senescence have been shown to increase with age and degeneration of human disc tissue. Senescent disc cells in culture recapitulate features associated with age-related disc degeneration, including increased secretion of proinflammatory cytokines, matrix proteases, and fragmentation of matrix proteins. However, little is known of the metabolic changes that underlie the senescent phenotype of disc cells. To assess the metabolic changes, we performed a bioenergetic analysis of in vitro oxidative stress-induced senescent (SIS) human disc cells. SIS disc cells acquire SASP and exhibit significantly elevated mitochondrial content and mitochondrial ATP-linked respiration. The metabolic changes appear to be driven by the upregulated protein secretion in SIS cells as abrogation of protein synthesis using cycloheximide decreased mitochondrial ATP-linked respiration. Taken together, the results of the study suggest that the increased energy generation state supports the secretion of senescent associated proteins in SIS disc cells.

Fractures of the odontoid present frequently in spinal trauma, and Type II odontoid fractures, occurring at the junction of the odontoid process and C2 vertebrae, represent the bulk of all traumatic odontoid fractures. It is currently unclear what soft-tissue stabilizers contribute to upper cervical motion in the setting of a Type II odontoid fracture, and evaluation of how concomitant injury contributes to cervical stability may inform surgical decision-making as well as allow for the creation of future, accurate, biomechanical models of the upper cervical spine. The objective of the current study was to determine the contribution of soft-tissue stabilizers in the upper cervical spine following a Type II odontoid fracture. Eight cadaveric C0-C2 specimens were evaluated using a robotic testing system with motion tracking. The unilateral facet capsule (UFC) and anterior longitudinal ligament (ALL) were serially resected to determine their biomechanical role following odontoid fracture. Range of motion (ROM) and moment at the end of intact specimen replay were the primary outcomes. We determined that fracture of the odontoid significantly increases motion and decreases resistance to intact motion for flexion-extension (FE), axial rotation (AR), and lateral bending (LB). Injury to the UFC increased AR by 3.2° and FE by 3.2°. ALL resection did not significantly increase ROM or decrease end-point moment. The UFC was determined to contribute to 19% of intact flexion resistance and 24% of intact AR resistance. Overall, we determined that Type II fracture of the odontoid is a significant biomechanical destabilizer and that concurrent injury to the UFC further increases upper cervical ROM and decreases resistance to motion in a cadaveric model of traumatic Type II odontoid fractures.

Objectives To evaluate how a comprehensive evidence-based clinical review by a multidisciplinary revascularization heart team on treatment decisions for revascularization in patients with complex coronary artery disease using SYNTAX scores combined with Society of Thoracic Surgeons-derived clinical variables can be additive to the utilization of Appropriate Use Criteria for coronary revascularization. Background Decision-making regarding the use of revascularization for coronary artery disease has come under major scrutiny due to inappropriate overuse of revascularization. There is little data in routine clinical practice evaluating how a structured, multidisciplinary heart team approach may be used in combination with the Appropriate Use Criteria for revascularization. Methods From May 1, 2012 to January 1, 2015, multidisciplinary revascularization heart team meetings were convened to discuss evidence-based management of 301 patients with complex coronary artery disease. Heart team recommendations were adjudicated with the Appropriate Use Criteria for coronary revascularization for each clinical scenario using the Society for Cardiovascular Angiography and Interventions' Quality Improvement Toolkit (SCAI-QIT) Appropriate Use Criteria App. Results Concordance of the Heart Team to Appropriate Use Criteria had a 99.3% appropriate primary indication for coronary revascularization. Among patients who underwent percutaneous revascularization, 34.9% had an inappropriate or uncertain indication as recommended by the Heart Team. Patients with uncertain or inappropriate percutaneous coronary interventions had significantly higher SYNTAX score (27.3 ± 6.6; 28.5 ± 5.5; 19.2 ± 6; P

Although substantial research demonstrates that intervertebral disc cells respond to mechanical signals, little research has been done to characterize the in vivo mechanical environment in the disc tissue. The objective of this study was to estimate cervical disc strain during three-dimensional head movements. Twenty-nine young healthy adults performed full range of motion flexion/extension, lateral bending, and axial rotation of the head within a biplane radiography system. Three-dimensional vertebral kinematics were determined using a validated model-based tracking technique. A computational model used these kinematics to estimate subject-specific intervertebral disc deformation (C3-4 to C6-7). Peak compression, distraction and shear strains were calculated for each movement, disc level, and disc region. Peak compression strain and peak shear strain were highest during flexion/extension (mean ± 95% confidence interval) (32 ± 3 and 86 ± 8%, respectively), while peak distraction strain was highest during lateral bending (57 ± 5%). Peak compression strain occurred at C4-5 (33 ± 4%), while peak distraction and shear strain occurred at C3-4 (54 ± 8 and 83 ± 11%, respectively). Peak compression, distraction, and shear strains all occurred in the posterior-lateral annulus (48 ± 4, 80 ± 8, and 109 ± 12%, respectively). These peak strain values may serve as boundary conditions for in vitro loading paradigms that aim to assess the biologic response to physiologic disc deformations.

Long-term data on outcomes after percutaneous coronary intervention (PCI) with drug-eluting stent (DES) and bare-metal stent (BMS) across racial groups are limited, and minorities are under-represented in existing clinical trials. Whether DES has better long-term clinical outcomes compared to BMS across racial groups remains to be established. Accordingly, we assessed whether longer-term clinical outcomes are better with DES compared to BMS across racial groups.Using the multicenter National Heart, Lung, and Blood Institute (NHLBI)-sponsored Dynamic Registry, 2-year safety (death, MI) and efficacy (repeat revascularization) outcomes of 3326 patients who underwent PCI with DES versus BMS were evaluated.With propensity-score adjusted analysis, the use of DES, compared to BMS, was associated with a lower risk for death or MI at 2 years for both blacks (adjusted Hazard Ratio (aHR)=0.41, 95% CI 0.25-0.69, p0.001) and whites (aHR=0.67, 95% CI 0.51-0.90, p=0.007). DES use was associated with a significant 24% lower risk of repeat revascularization in whites (aHR=0.76, 95% CI 0.60-0.97, p=0.03) and with nominal 34% lower risk in blacks (aHR=0.66, 95% CI 0.39-1.13, p=0.13).The use of DES in PCI was associated with better long-term safety outcomes across racial groups. Compared to BMS, DES was more effective in reducing repeat revascularization in whites and blacks, but this benefit was attenuated after statistical adjustment in blacks. These findings indicate that DES is superior to BMS in all patients regardless of race. Further studies are needed to determine long-term outcomes across racial groups with newer generation stents.

Objectives To provide an up-to-date analysis on the relationship between excise taxes and the prevalence of cigarette smoking in the United States. Methods Linear mixed-effects models were used to model the relationship between excise taxes and prevalence of cigarette smoking in each state from 2001 through 2015. Results From 2001 through 2015, increases in state-level excise taxes were associated with declines in prevalence of cigarette smoking. The effect was strongest in young adults (age 18–24) and weakest in low-income individuals (

ObjectivesTo determine the prevalence and factors associated with persistent pulmonary hypertension (PH) following transcatheter aortic valve replacement (TAVR) and its relationship with long-term mortality.MethodsConsecutive patients who underwent TAVR from July 2011 through January 2016 were studied. The prevalence of baseline PH (mean pulmonary artery pressure ≥25 mm Hg on right heart catheterisation) and the prevalence and the predictors of persistent≥moderate PH (pulmonary artery systolic pressure (PASP)>45 mm Hg on 1 month post-TAVR transthoracic Doppler echocardiography) were collected. Cox models quantified the effect of persistent PH on subsequent mortality while adjusting for confounders.ResultsOf the 407 TAVR patients, 273 (67%) had PH at baseline. Of these, 102 (25%) had persistent≥moderate PH. Mortality at 2 years in patients with no baseline PH versus those with PH improvement (follow-up PASP≤45 mm Hg) versus those with persistent≥moderate PH was 15.4%, 16.6% and 31.3%, respectively (p=0.049). After adjusting for Society of Thoracic Surgeons Predicted Risk of Mortality and baseline right ventricular function (using tricuspid annular plane systolic excursion), persistent≥moderate PH remained associated with all-cause mortality (HR=1.82, 95% CI 1.06 to 3.12, p=0.03). Baseline characteristics associated with increased likelihood of persistent≥moderate PH were ≥moderate tricuspid regurgitation, ≥moderate mitral regurgitation, atrial fibrillation/flutter, early (E) to late (A) ventricular filling velocities (E/A ratio) and left atrial volume index.ConclusionsPersistency of even moderate or greater PH at 1 month post-TAVR is common and associated with higher all-cause mortality.

ADAMTS5-deficient and wild type (WT) mice were chronically exposed to tobacco smoke to investigate effects on intervertebral disc degeneration (IDD).The aim of this study was to demonstrate a role for ADAMTS5 in mediating tobacco smoking-induced IDD.We previously demonstrated that chronic tobacco smoking causes IDD in mice because, in part, of proteolytic destruction of disc aggrecan. However, it was unknown which matrix proteinase(s) drive these detrimental effects.Three-month-old WT (C57BL/6) and ADAMTS5 mice were chronically exposed to tobacco smoke (four cigarettes/day, 5 day/week for 6 months). ADAMTS-mediated cleavage of disc aggrecan was analyzed by Western blot. Disc total glycosaminoglycan (GAG) content was assessed by dimethyl methylene blue assay and safranin O/fast green histology. Vertebral osteoporosity was measured by microcomputed tomography. Human nucleus pulposus (hNP) cell cultures were also exposed directly to tobacco smoke extract (TSE), a condensate containing the water-soluble compounds inhaled by smokers, to measure ADAMTS5 expression and ADAMTS-mediated cleavage of aggrecan. Activation of nuclear factor (NF)-κB, a family of transcription factors essential for modulating the cellular response to stress, was measured by immunofluorescence assay.Genetic depletion of ADAMTS5 prevented vertebral bone loss, substantially reduced loss of disc GAG content, and completely obviated ADAMTS-mediated proteolysis of disc aggrecan within its interglobular domain (IGD) in mice following exposure to tobacco smoke. hNP cell cultures exposed to TSE also resulted in upregulation of ADAMTS5 protein expression and a concomitant increase in ADAMTS-mediated cleavage within aggrecan IGD. Activation of NF-κB, known to be required for ADAMTS5 gene expression, was observed in both TSE-treated hNP cell cultures and disc tissue of tobacco smoke-exposed mice.The findings demonstrate that ADAMTS5 is the primary aggrecanase mediating smoking-induced disc aggrecanolysis and IDD. Mouse models of chronic tobacco smoking are important and useful for probing the mechanisms of disc aggrecan catabolism and IDD.N/A.

Background Non-invasive cardiac imaging allows detection of cardiac amyloidosis (CA) in patients with aortic stenosis (AS). Our objective was to estimate the prevalence of clinically suspected CA in patients with moderate and severe AS referred for cardiovascular magnetic resonance (CMR) in age and gender categories, and assess associations between AS-CA and all-cause mortality. Methods We retrospectively identified consecutive AS patients defined by echocardiography referred for further CMR assessment of valvular, myocardial, and aortic disease. CMR identified CA based on typical late-gadolinium enhancement (LGE) patterns, and ancillary clinical evaluation identified suspected CA. Survival analysis with the Log rank test and Cox regression compared associations between CA and mortality. Results There were 113 patients (median age 74 years, Q1-Q3: 62–82 years), 96 (85%) with severe AS. Suspected CA was present in 9 patients (8%) all > 80 years. Among those over the median age of 74 years, the prevalence of CA was 9/57 (16%), and excluding women, the prevalence was 8/25 (32%). Low-flow, low-gradient physiology was very common in CA (7/9 patients or 78%). Over a median follow-up of 18 months, 40 deaths (35%) occurred. Mortality in AS + CA patients was higher than AS alone (56% vs. 20% at 1-year, log rank 15.0, P

In total, 496 patients of a single surgeon cohort examining the surgical-site infection (SSI) rates with the addition of vancomycin powder in both diabetic and revision spine surgery cases. A historical control group of 652 patients were compared from the same surgeon over an earlier time period before the inception of using vancomycin powder prophylaxis.The objective of this study was to describe and compare the rates of infection in high-risk patient populations while using vancomycin powder.Vancomycin powder may not decrease an already low rate of infection. Therefore, use of vancomycin powder in high-risk patients with a higher rate of infection would potentially show benefit of vancomycin powder.In total, 496 patient charts were collected from a database of cases. Patients were included in the cohort if they had revision spinal operation or if they were diabetic. Patients in the time period July 2010 to August 2013 were included in the vancomycin protocol where 1 g of vancomycin powder was added to the wound before wound closure. Cases were considered positive if there was a positive culture or if there was sufficient clinical suspicion to treat. As a control to this cohort, 692 charts were reviewed from a earlier time period of the same surgeon and institution.In total, 28 patients of 496 (5.6%) patients in the cohort returned to the operating room for seroma, hematoma, draining wound, or infection. Sixteen of these patients (16/496, 3.2%) had a culture positive infection or were treated as an infection. This rate was significantly lower than the historical rate before the protocol.Although vancomycin does seem to be useful in decreasing SSIs, it is not a panacea. SSIs in high-risk patients were not completely eliminated by the vancomycin protocol.

Background As a result of the focus on vital functions in patients with brain damage, dermatological symptoms are often overlooked during their period of admission to hospital. However, patients with brain damage are more likely to have dermatological diseases than the general population and other inpatients for various reasons, including immobilization, treatment with multiple drugs, long-term hospitalization, and their immunocompromised status. Objectives The purposes of this study were: (1) to analyze the frequency and characteristics of dermatological consultations among patients who were admitted to hospital as a result of brain damage; and (2) to compare these findings with other reports about inpatient dermatological consultations. Methods We analyzed data for 240 patients with brain damage who attended our department of dermatology between January 1, 2007 and December 31, 2011. The total numbers of male and female patients were 132 (55%) and 108 (45%), respectively (male to female ratio 1.22:1). We retrospectively reviewed medical records, demographic information, reason for dermatological consultation, and the diagnosis of the dermatoses. Results The age group most frequently seen was patients in the 7 th decade of life and the most common underlying brain injury was traumatic intracranial hemorrhage. The mean±standard deviation score on the Glasgow Coma Scale (GCS) was 6.8±3.0. When the levels of brain damage of the patients were classified using the GCS, 68.3% of the patients were in the severe (GCS≤8) category. The most common skin disorders were seborrheic dermatitis (17.9%), followed by mycoses (15.5%), and drug-induced skin eruption (13.2%). Conclusion The characteristics of dermatological consultations in patients with brain damage may be different from those of other inpatients attending dermatological clinics. The analysis of dermatological disorders in patients with brain damage can assist in understanding the "brain–skin connection".

The objective of this study was to demonstrate how a load cell and force-moment curves can be used outside of a gait lab to directly measure and evaluate the transverse plane loading moment on transtibial residual limbs.A load cell was attached distally to the socket of three transtibial amputees who walked a straight path and a circle of 3.048-m diameter with the prosthetic foot both inside and outside the curved path.Compared to straight path walking, transverse plane moment decreased when the foot was on the outside of the curved path. When the foot was on the inside, the moment did not exceed that for straight path walking for two participants; maximum transverse moment was approximately 0.15 N m/kg of body mass. Force-moment curves indicated that each participant's gait was unique, but underlying similarities were observed with respect to each of the three conditions.A load cell in conjunction with curved and straight path walking and force-moment curves can be used outside of a gait lab to measure and examine the transverse plane loading on the residual limb.

A simple and conventional PECVD method was adopted to synthesize scratch-resistant hydrophobic and oleophobic films, by varying the process condition. The film was designed to be 3 layered. The first SiOx layer was coated on the substrate using OMCTS and O2, followed by O2 plasma treatment; hydrocarbon-based hydrophobic film was synthesized using HMDS as a second layer; and finally, CFx-based film was coated using C2F6. The first and second layers were synthesized using RF power of 13.56 MHz, while MF power of 40 kHz was used for the CFx layer for ion-assisted deposition. The water contact angle was measured to be 110°–115°, and the oil contact angle was 84° for the best obtained sample. The pencil hardness was measured to be 7H for anti-scratch property. XPS was adopted to analyze the chemical structure and showed that highly cross-linked dense structured film was synthesized.

Few studies have evaluated outcomes following percutaneous coronary intervention (PCI) in patients with both anemia and chronic kidney disease (CKD). Patients who underwent PCI in our health system from 2010-2018 were included (n=10,756), excluding those with ST-elevation myocardial infarction or