Endophytic fungus from Handroanthus impetiginosus immobilized on electrospun nanofibrous membrane for bioremoval of bisphenol A.

The current industrial and human activities scenario has accelerated the widespread use of endocrine-disrupting compounds (EDCs), which can be found in everyday products, including plastic containers, bottles, toys, cosmetics, etc., but can pose a severe risk to human health and the environment. In this regard, fungal bioremediation appears as a green and cost-effective approach to removing pollutants from water resources. Besides, immobilizing fungal cells onto nanofibrous membranes appears as an innovative strategy to improve remediation performance by allowing the adsorption and degradation to occur simultaneously. Herein, we developed a novel nanostructured bioremediation platform based on polyacrylonitrile nanofibrous membrane (PAN NFM) as supporting material for immobilizing an endophytic fungus to remove bisphenol A (BPA), a typical EDC. The endophytic strain was isolated from Handroanthus impetiginosus leaves and identified as Phanerochaete sp. H2 by molecular methods. The successful assembly of fungus onto the PAN NFM surface was confirmed by scanning electron microscopy (SEM). Compared with free fungus cells, the PAN@H2 NFM displayed a high BPA removal efficiency (above 85%) at an initial concentration of 5 ppm, suggesting synergistic removal by simultaneous adsorption and biotransformation. Moreover, the biotransformation pathway was investigated, and the chemical structures of fungal metabolites of BPA were identified by ultra-high performance liquid chromatography - high-resolution mass (UHPLC-HRMS) analysis. In general, our results suggest that by combining the advantages of enzymatic activity and nanofibrous structure, the novel platform has the potential to be applied in the bioremediation of varied EDCs or even other pollutants found in water resources.

Alternative human eIF5A protein isoform plays a critical role in mitochondria.

The eukaryotic translation initiation factor 5A (eIF5A) is the only known protein containing the amino acid residue hypusine, essential for its activity. Hypusine residue is produced by a posttranslational modification involving deoxyhypusine synthetase and deoxyhypusine hydroxylase. Herein, we aimed to describe the role of the alternative human isoform A on mitochondrial processes. Isoform A depletion modulates oxidative metabolism in association with the downregulation of mitochondrial biogenesis-related genes. Through positive feedback, it increases cell respiration leading to highly reactive oxygen species production, which impacts mitochondrial bioenergetics. These metabolic changes compromise mitochondrial morphology, increasing its electron density and fission, observed by transmission electron microscopy. This set of changes leads the cells to apoptosis, evidenced by increased DNA fragmentation and proapoptotic BAK protein content increase. Thus, we show that the alternative eIF5A isoform A is crucial for energy metabolism controlled by mitochondria and cellular survival.

Self-expanding intra-annular versus commercially available transcatheter heart valves in high and extreme risk patients with severe aortic stenosis (PORTICO IDE): a randomised, controlled, non-inferiority trial.

BACKGROUND: Randomised trial data assessing the safety and efficacy of the self-expanding intra-annular Portico transcatheter aortic valve system (Abbott Structural Heart, St Paul, MN, USA) compared with any commercially available valves are needed to compare performance among designs. METHODS: In this prospective, multicentre, non-inferiority, randomised controlled trial (the Portico Re-sheathable Transcatheter Aortic Valve System US Investigational Device Exemption trial [PORTICO IDE]), high and extreme risk patients with severe symptomatic aortic stenosis were recruited from 52 medical centres experienced in performing transcatheter aortic valve replacement in the USA and Australia. Patients were eligible if they were aged 21 years or older, in New York Heart Association functional class II or higher, and had severe native aortic stenosis. Eligible patients were randomly assigned (1:1) using permuted block randomisation (block sizes of 2 and 4) and stratified by clinical investigational site, surgical risk cohort, and vascular access method, to transcatheter aortic valve replacement with the first generation Portico valve and delivery system or a commercially available valve (either an intra-annular balloon-expandable Edwards-SAPIEN, SAPIEN XT, or SAPIEN 3 valve [Edwards LifeSciences, Irvine, CA, USA]; or a supra-annular self-expanding CoreValve, Evolut-R, or Evolut-PRO valve [Medtronic, Minneapolis, MN, USA]). Investigational site staff, implanting physician, and study participant were unmasked to treatment assignment. Core laboratories and clinical event assessors were masked to treatment allocation. The primary safety endpoint was a composite of all-cause mortality, disabling stroke, life-threatening bleeding requiring transfusion, acute kidney injury requiring dialysis, or major vascular complication at 30 days. The primary efficacy endpoint was all-cause mortality or disabling stroke at 1 year. Clinical outcomes and valve performance were assessed up to 2 years after the procedure. Primary analyses were by intention to treat and the Kaplan-Meier method to estimate event rates. The non-inferiority margin was 8·5% for primary safety and 8·0% for primary efficacy endpoints. This study is registered with ClinicalTrials.gov, NCT02000115, and is ongoing. FINDINGS: Between May 30 and Sept 12, 2014, and between Aug 21, 2015, and Oct 10, 2017, with recruitment paused for 11 months by the funder, we recruited 1034 patients, of whom 750 were eligible and randomly assigned to the Portico valve group (n=381) or commercially available valve group (n=369). Mean age was 83 years (SD 7) and 395 (52·7%) patients were female. For the primary safety endpoint at 30 days, the event rate was higher in the Portico valve group than in the commercial valve group (52 [13·8%] vs 35 [9·6%]; absolute difference 4·2, 95% CI -0·4 to 8·8 [upper confidence bound {UCB} 8·1%]; pnon-inferiority=0·034, psuperiority=0·071). At 1 year, the rates of the primary efficacy endpoint were similar between the groups (55 [14·8%] in the Portico group vs 48 [13·4%] in the commercial valve group; difference 1·5%, 95% CI -3·6 to 6·5 [UCB 5·7%]; pnon-inferiority=0·0058, psuperiority=0·50). At 2 years, rates of death (80 [22·3%] vs 70 [20·2%]; p=0·40) or disabling stroke (10 [3·1%] vs 16 [5·0%]; p=0·23) were similar between groups. INTERPRETATION: The Portico valve was associated with similar rates of death or disabling stroke at 2 years compared with commercial valves, but was associated with higher rates of the primary composite safety endpoint including death at 30 days. The first-generation Portico valve and delivery system did not offer advantages over other commercially available valves. FUNDING: Abbott.

Behçet disease, new insights in disease associations and manifestations: a next-generation sequencing study.

Behçet disease is a multi-system disease associated with human leukocyte antigen (HLA) class I polymorphism. High-resolution next-generation sequencing (NGS) with haplotype analysis has not been performed previously for this disease. Sixty Egyptian patients diagnosed according to the International Study Group (ISG) criteria for Behçet disease and 160 healthy geographic and ethnic-matched controls were genotyped for HLA class I loci (HLA-A, B, C). For HLA class II loci (DRB1, DRB3/4/5, DQA1, DQB1, DPA1, DPB1), 40 control samples were genotyped. High-resolution HLA genotyping was performed using NGS and the results were analyzed. Clinical manifestations were oral ulcers (100%), genital ulcers (100%), eye (55%) and neurological (28%) and vascular involvement (35%). HLA-B*51:08 [odds ratio (OR) = 19·75, 95% confidence interval (CI) = 6·5-79; P < 0·0001], HLA-B*15:03 (OR = 12·15, 95% CI = 3·7-50·7; P < 0·0001), HLA-C*16:02 (OR = 6·53, 95% CI = 3-14; P < 0·0001), HLA-A*68:02 (OR = 3·14, 95% CI = 1·1-8·9; P < 0·01) were found to be associated with Behçet disease, as were HLA-DRB1*13:01 and HLA-DQB1*06:03 (OR = 3·39, 95% CI = 0·9-18·9; P = 0·04 for both). By contrast, HLA-A*03:01 (OR = 0·13, 95% CI = 0-0·8; P = 0·01) and HLA-DPB1*17:01 were found to be protective (OR = 0·27, 95% CI = 0·06-1·03; P = 0·02). We identified strong linkage disequilibrium between HLA-B*51:08 and C*16:02 and A*02:01 in a haplotype associated with Behçet disease. HLA-B*51:08 was significantly associated with legal blindness (OR = 2·98, 95% CI = 1·06-8·3; P = 0·01). In Egyptian Behçet patients, HLA-B*51:08 is the most common susceptibility allele and holds poor prognosis for eye involvement.

Drug Repositioning in Oncology.

BACKGROUND: The worldwide increase in the occurrence of cancer associated with the limitations of immunotherapy and the emergence of resistance have impaired the prognosis of cancer patients, which leads to the search for alternative treatment methods. Drug repositioning, a well-established process approved by regulatory agencies, is considered an alternative strategy for the fast identification of drugs, because it is relatively less costly and represents lower risks for patients. AREAS OF UNCERTAINTY: We report the most relevant studies about drug repositioning in oncology, emphasizing that its implementation faces financial and regulatory obstacles, making the creation of incentives necessary to stimulate the involvement of the pharmaceutical industry. DATA SOURCES: We present 63 studies in which 52 non-anticancer drugs with anticancer activity against a number of malignancies are described. THERAPEUTIC INNOVATIONS: Some have already been the target of phase III studies, such as the Add-Aspirin trial for nonmetastatic solid tumors, as well as 9 other drugs (aprepitant, artesunate, auranofin, captopril, celecoxib, disulfiram, itraconazole, ritonavir, and sertraline) in the CUSP9* clinical trial for the treatment of recurrent glioblastoma. Others have already been successful in repositioning such as thalidomide, zoledronic acid, celecoxib, methotrexate, and gemcitabine. CONCLUSIONS: Therefore, drug repositioning represents a promising alternative for the treatment of oncological disorders; however, the support from funding agencies and from the government is still needed, the latter regarding regulatory issues.

A novel technique to produce tubular scaffolds based on collagen and elastin.

Tubular polymer scaffolds based on tissue engineering techniques have been studied as potential alternatives for vascular regeneration implants. The blood vessels of the cardiovascular system are mainly fibrous, composed of collagen (Col) and elastin (El), and its inner layer consists of endothelial cells. In this work, Col and El were combined with polyurethane (PU), a biocompatible synthetic polymer, and rotary jet spinning, a new and highly productive technique, to produce fibrous scaffolds. The scaffolds produced at 18 000 rpm presented homogeneous, bead-free, and solvent-free fibers. The blend formation between PU-Col-El was identified by chemical composition analysis and enhanced the thermal stability up to 324°C. The hydrophilic nature of the scaffold was revealed by its low contact angle. Cell viability of human umbilical vein endothelial cells with the scaffold was proven for 72 hours. The combined strategy of rotary jet spinning with a polymer blend containing Col and El was verified as an effective and promising alternative to obtain tubular scaffolds for tissue engineering on a large-scale production.

Combined forced oscillation and fractional-order modeling in patients with work-related asthma: a case-control study analyzing respiratory biomechanics and diagnostic accuracy.

BACKGROUND: Fractional-order (FrOr) models have a high potential to improve pulmonary science. These models could be useful for biomechanical studies and diagnostic purposes, offering accurate models with an improved ability to describe nature. This paper evaluates the performance of the Forced Oscillation (FO) associated with integer (InOr) and FrOr models in the analysis of respiratory alterations in work-related asthma (WRA). METHODS: Sixty-two individuals were evaluated: 31 healthy and 31 with WRA with mild obstruction. Patients were analyzed pre- and post-bronchodilation. The diagnostic accuracy was evaluated using the area under the receiver operating characteristic curve (AUC). To evaluate how well do the studied models correspond to observed data, we analyzed the mean square root of the sum (MSEt) and the relative distance (Rd) of the estimated model values to the measured resistance and reactance measured values. RESULTS AND DISCUSSION: Initially, the use of InOr and FrOr models increased our understanding of the WRA physiopathology, showing increased peripheral resistance, damping, and hysteresivity. The FrOr model (AUC = 0.970) outperformed standard FO (AUC = 0.929), as well as InOr modeling (AUC = 0.838) in the diagnosis of respiratory changes, achieving high accuracy. FrOr improved the curve fitting (MSEt = 0.156 ± 0.340; Rd = 3.026 ± 1.072) in comparison with the InOr model (MSEt = 0.367 ± 0.991; Rd = 3.363 ± 1.098). Finally, we demonstrated that bronchodilator use increased dynamic compliance, as well as reduced damping and peripheral resistance. CONCLUSIONS: Taken together, these results show clear evidence of the utility of FO associated with fractional-order modeling in patients with WRA, improving our knowledge of the biomechanical abnormalities and the diagnostic accuracy in this disease.

Loss of Parkin Results in Altered Muscle Stem Cell Differentiation during Regeneration.

The high capacity of the skeletal muscle to regenerate is due to the presence of muscle stem cells (MuSCs, or satellite cells). The E3 ubiquitin ligase Parkin is a key regulator of mitophagy and is recruited to mitochondria during differentiation of mouse myoblast cell line. However, the function of mitophagy during regeneration has not been investigated in vivo. Here, we have utilized Parkin deficient (Parkin-/-) mice to investigate the role of Parkin in skeletal muscle regeneration. We found a persistent deficiency in skeletal muscle regeneration in Parkin-/- mice after cardiotoxin (CTX) injury with increased area of fibrosis and decreased cross-sectional area (CSA) of myofibres post-injury. There was also a significant modulation of MuSCs differentiation and mitophagic markers, with altered mitochondrial proteins during skeletal muscle regeneration in Parkin-/- mice. Our data suggest that Parkin-mediated mitophagy plays a key role in skeletal muscle regeneration and is necessary for MuSCs differentiation.

The polyproline-motif of S6K2: eIF5A translational dependence and importance for protein-protein interactions.

Ribosomal S6 kinase 1 (S6K1) and S6K2 proteins are effectors of the mammalian target of rapamycin complex 1 pathway, which control the process of protein synthesis in eukaryotes. S6K2 is associated with tumor progression and has a conserved C-terminus polyproline rich motif predicted to be important for S6K2 interactions. It is noteworthy that the translation of proteins containing sequential prolines has been proposed to be dependent of eukaryotic translation initiation factor 5A (eIF5A) translation factor. Therefore, we investigated the importance of polyproline-rich region of the S6K2 for its intrinsic phosphorylation activity, protein-protein interaction and eIF5A role in S6K2 translation. In HeLa cell line, replacing S6K2 polyproline by the homologous S6K1-sequence did not affect its kinase activity and the S6K2 endogenous content was maintained after eIF5A gene silencing, even after near complete depletion of eIF5A protein. Moreover, no changes in S6K2 transcript content was observed, ruling out the possibility of compensatory regulation by increasing the mRNA content. However, in the budding yeast model, we observed that S6K2 production was impaired when compared with S6K2∆Pro, after reduction of eIF5A protein content. These results suggest that although the polyproline region of S6K2 is capable of generating ribosomal stalling, the depletion of eIF5A in HeLa cells seems to be insufficient to cause an expressive decrease in the content of endogenous S6K2. Finally, coimmunoprecipitation assays revealed that the replacement of the polyproline motif of S6K2 alters its interactome and impairs its interaction with RPS6, a key modulator of ribosome activity. These results evidence the importance of S6K2 polyproline motif in the context of S6Ks function.

Transcatheter or Surgical Aortic-Valve Replacement in Intermediate-Risk Patients.

BACKGROUND: Previous trials have shown that among high-risk patients with aortic stenosis, survival rates are similar with transcatheter aortic-valve replacement (TAVR) and surgical aortic-valve replacement. We evaluated the two procedures in a randomized trial involving intermediate-risk patients. METHODS: We randomly assigned 2032 intermediate-risk patients with severe aortic stenosis, at 57 centers, to undergo either TAVR or surgical replacement. The primary end point was death from any cause or disabling stroke at 2 years. The primary hypothesis was that TAVR would not be inferior to surgical replacement. Before randomization, patients were entered into one of two cohorts on the basis of clinical and imaging findings; 76.3% of the patients were included in the transfemoral-access cohort and 23.7% in the transthoracic-access cohort. RESULTS: The rate of death from any cause or disabling stroke was similar in the TAVR group and the surgery group (P=0.001 for noninferiority). At 2 years, the Kaplan-Meier event rates were 19.3% in the TAVR group and 21.1% in the surgery group (hazard ratio in the TAVR group, 0.89; 95% confidence interval [CI], 0.73 to 1.09; P=0.25). In the transfemoral-access cohort, TAVR resulted in a lower rate of death or disabling stroke than surgery (hazard ratio, 0.79; 95% CI, 0.62 to 1.00; P=0.05), whereas in the transthoracic-access cohort, outcomes were similar in the two groups. TAVR resulted in larger aortic-valve areas than did surgery and also resulted in lower rates of acute kidney injury, severe bleeding, and new-onset atrial fibrillation; surgery resulted in fewer major vascular complications and less paravalvular aortic regurgitation. CONCLUSIONS: In intermediate-risk patients, TAVR was similar to surgical aortic-valve replacement with respect to the primary end point of death or disabling stroke. (Funded by Edwards Lifesciences; PARTNER 2 ClinicalTrials.gov number, NCT01314313.).

Long noncoding RNA polymorphisms influence susceptibility to endemic pemphigus foliaceus.

BACKGROUND: Pemphigus foliaceus (PF) is an epidermal autoimmune disease, characterized by the presence of autoantibodies against the desmosomal protein desmoglein 1. Genetic and environmental factors contribute to PF, a complex disease that is endemic in Brazil and Colombia and neighbouring countries, and in Tunisia. Long noncoding RNAs (lncRNAs) may participate in gene regulation by interacting with DNA, proteins and other RNAs. Dysregulation of lncRNAs has recently been recognized as an important coplayer in the onset or progression of complex diseases. In addition, single-nucleotide polymorphisms (SNPs) located in lncRNA genes have been associated with differential risk to cancer, autoimmunity and infection. OBJECTIVES: Here, we aimed to investigate whether SNPs in lncRNA genes are associated with differential susceptibility to endemic PF. MATERIALS AND METHODS: We integrated data from the lncRNA SNP database with genome-wide genotype data obtained for 229 patients and 6681 controls. We tested the association between endemic PF and 2080 SNPs located in lncRNAs applying logistic regression. RESULTS: The most significantly associated SNP was rs7144332 (OR = 1·63, P = 2·8 × 10-6 ), located in the lncRNA gene AL110292·1. Results for five other SNPs were suggestive of association (P < 0·001). In silico analysis indicated that five of the six SNPs impact transcription, three may influence lncRNA's secondary structure, and three may alter microRNA-lncRNA interactions. CONCLUSIONS: We showed, for the first time, that variation in lncRNA genes may influence pemphigus pathogenesis. Our findings highlight the importance of lncRNA variation in autoimmune and possibly other complex diseases and suggest polymorphisms for functional validation.

Comparison of coronary revascularization appropriateness for non-acute coronary syndrome cases under the 2017 update vs the 2012 appropriate use criteria.

OBJECTIVES: To compare coronary revascularization appropriateness for non-acute coronary syndrome cases under the 2017 update vs the 2012 appropriate use criteria (AUC). BACKGROUND: In 2017, the 2012 AUC for coronary revascularization were updated. We examined how applying these new 2017 updates to our previous inappropriate cases would change their appropriateness. METHODS: We identified 50 cases of patients who underwent coronary revascularization for stable ischemic heart disease who were deemed inappropriate under the 2012 AUC. Two separate physicians reviewed the cases and applied a new AUC based on the 2017 AUC. Next, if there was a change, the reason was identified. RESULTS: Average age was 64, majority being male (29; 58%). Forty-two (84%) were asymptomatic upon presentation. Most cases (27, 54%) dealt with percutaneous coronary intervention (PCI) of the right coronary artery. After applying the 2017 AUC, 34 of the 50 inappropriate failures (68%) would be changed from "inappropriate" to "may be appropriate care." Of the 34 cases, 25 (73.5%) were changed due to the new AUC no longer expecting the patient to be on ≥2 anti-angina medications prior to PCI. Of the 34 cases, eight (23.5%) were changed due to the new AUC expanding the use of non-invasive modalities. CONCLUSIONS: Applying the 2017 AUC led to a statistically higher number of cases being deemed "may be appropriate." The most common cause for the change included the change in requirement for anti-angina regimen and the expanded role of non-invasive modalities.

Role of contractile reserve as a predictor of mortality in low-flow, low-gradient severe aortic stenosis following transcatheter aortic valve replacement.

OBJECTIVES: The aim of this study was to determine the prognostic value of contractile reserve (CR) at baseline in patients with low-flow, low-gradient severe aortic stenosis (AS) undergoing transcatheter aortic valve replacement (TAVR). BACKGROUND: Patients with severe AS, left ventricular dysfunction, and low transaortic gradient are at high risk for mortality during surgical aortic valve replacement (SAVR). Furthermore, patients without CR have been shown to have perioperative mortality comparable to that of patients treated medically for severe AS. METHODS: We retrospectively analyzed patients who underwent TAVR with a diagnosis of low-gradient severe AS (mean transvalvular aortic gradient < 40 mmHg, LVEF < 50%, and AVA ≤ 1.0 cm2 or AVAi ≤ 0.6 cm2 ) and who had a pre-TAVR dobutamine stress echocardiogram (DSE). Patients were stratified by the presence or absence of CR, defined as an increase in stroke volume ≥ 20% during DSE. RESULTS: From 2008 to 2016, 61 patients with low-gradient severe AS underwent TAVR and had pre-TAVR DSE. CR was present in 31 patients (51%) and absent in 30 (49%). There was no significant difference between the two groups in baseline demographics, medical history, access site, or types of valves. All-cause mortality was similar in both groups at 30 days (13% with CR vs 10% without CR, P = 1.00) and 1 year (29% with CR vs 33% without CR, HR 1.20, 95% CI 0.49-2.96, P = 0.69). CONCLUSION: In patients with low-flow, low-gradient severe AS undergoing TAVR, the presence or absence of CR does not predict all-cause mortality at 30 days or 1 year.

Possible Subclinical Leaflet Thrombosis in Bioprosthetic Aortic Valves.

BACKGROUND: A finding of reduced aortic-valve leaflet motion was noted on computed tomography (CT) in a patient who had a stroke after transcatheter aortic-valve replacement (TAVR) during an ongoing clinical trial. This finding raised a concern about possible subclinical leaflet thrombosis and prompted further investigation. METHODS: We analyzed data obtained from 55 patients in a clinical trial of TAVR and from two single-center registries that included 132 patients who were undergoing either TAVR or surgical aortic-valve bioprosthesis implantation. We obtained four-dimensional, volume-rendered CT scans along with data on anticoagulation and clinical outcomes (including strokes and transient ischemic attacks [TIAs]). RESULTS: Reduced leaflet motion was noted on CT in 22 of 55 patients (40%) in the clinical trial and in 17 of 132 patients (13%) in the two registries. Reduced leaflet motion was detected among patients with multiple bioprosthesis types, including transcatheter and surgical bioprostheses. Therapeutic anticoagulation with warfarin, as compared with dual antiplatelet therapy, was associated with a decreased incidence of reduced leaflet motion (0% and 55%, respectively, P=0.01 in the clinical trial; and 0% and 29%, respectively, P=0.04 in the pooled registries). In patients who were reevaluated with follow-up CT, restoration of leaflet motion was noted in all 11 patients who were receiving anticoagulation and in 1 of 10 patients who were not receiving anticoagulation (P<0.001). There was no significant difference in the incidence of stroke or TIA between patients with reduced leaflet motion and those with normal leaflet motion in the clinical trial (2 of 22 patients and 0 of 33 patients, respectively; P=0.16), although in the pooled registries, a significant difference was detected (3 of 17 patients and 1 of 115 patients, respectively; P=0.007). CONCLUSIONS: Reduced aortic-valve leaflet motion was shown in patients with bioprosthetic aortic valves. The condition resolved with therapeutic anticoagulation. The effect of this finding on clinical outcomes including stroke needs further investigation. (Funded by St. Jude Medical and Cedars-Sinai Heart Institute; Portico-IDE ClinicalTrials.gov number, NCT02000115; SAVORY registry, NCT02426307; and RESOLVE registry, NCT02318342.).

Utility of an additive frailty tests index score for mortality risk assessment following transcatheter aortic valve replacement.

BACKGROUND: The impact of frailty assessment on outcomes in patients undergoing transcatheter aortic valve replacement (TAVR) remains unclear. Our aim was to evaluate the individual effect of each frailty test and the utility of an additive frailty index score on short- and long-term survival following TAVR. METHODS: Retrospective analysis of consecutive TAVR patients for whom a complete set of frailty tests was obtained: algorithm defined grip strength and 5-m walking tests, body mass index <20 kg/m2, Katz activities of daily living ≤4/6, serum albumin <3.5 g/dL. Frailty status was defined as having 3 or more positive frailty tests. Included were 498 patients with a mean age of 82±8 years. RESULTS: Frailty status, observed in 266 (53%) patients, was associated with both 30-day and 1-year mortality (6% vs. 2%, P=.016; 20% vs. 9%, P<.001; within the respective frailty groups). As compared to 0-2 frailty criteria, a higher frailty index score was associated with increased risk of death at 1 year (OR 2.23; 95% CI 1.14-4.34; P=.019 and OR 3.30; 95% CI 1.36-8.00; P=.008 for 3 and 4-5 frailty criteria met, respectively). In Cox regression analysis, frailty status was correlated with 1-year mortality (HR=2.2; 95%CI 1.25-3.96; P=.007), and a higher frailty index was associated with increased mortality risk (HR=2.0; 95% CI 1.08-3.7; P=.027; and HR=3.07; 95% CI 1.4-6.7; P=.005; for any 3, and 4-5 frailty criteria, respectively). CONCLUSIONS: Frailty status and a higher frailty index score were associated with increased 1-year mortality risk following TAVR.

The use of needle holders in CTF guided biopsies as a dose reduction tool.

PURPOSE: The purpose of this study was to evaluate the efficacy of needle holders in reducing staff hand exposure during biopsies guided by computed tomography fluoroscopy (CTF), through the analysis of data acquired during a detailed monitoring study, undertaken in parallel with an ongoing optimization process to reduce hand irradiation. METHODS: Hand monitoring was performed with 11 extremity detectors, two per finger (base and tip) and one on the back of the wrist, for the left (dominant) hand, during two series of biopsies with comparable characteristics. The first series (47 biopsies) were performed with only quick-check method (QC) and occasional side-handle (SH) manipulation of the needle. The second series (63 biopsies) were performed after introducing needle holders (NH) in the course of an optimization process. RESULTS: Choice of technique (QC, QC + NH, QC + SH) by the interventional radiologist (IR) was related to biopsy difficulty. Measured hand exposure was low (< 1 mSv) for all QC-only procedures, and for most of the QC + NH procedures. Occasional side-handle manipulation still occurred during challenging biopsies, so that 8% of biopsies in the second series accounted for ~70% of total fingertip dose (~90 mSv). The methodology used allowed a detailed insight into the dose reduction achievable with needle holders during real procedures, without the limitations of phantom measurements. CONCLUSIONS: Needle holders proved effective in reducing mean hand exposure during clinical procedures where real-time manipulation was necessary. Occasional side-handle manipulation was found to contribute disproportionately to hand exposure. This highlights the importance of individual hand monitoring during CTF guided procedures.

Impact of right ventricular function on outcome of severe aortic stenosis patients undergoing transcatheter aortic valve replacement.

BACKGROUND: Right ventricular (RV) dysfunction was shown to be associated with adverse outcomes in a variety of cardiac patients and is considered a risk factor for adverse outcome according to the updated Valve Academic Research Consortium criteria. OBJECTIVE: Our goal was to assess the impact of RV function at baseline on 1-year mortality among patients with severe aortic stenosis (AS) undergoing transcatheter aortic valve replacement (TAVR). METHODS: All patients with severe AS treated with TAVR from May 2007 to March 2015 at our center were included in the present study, and baseline and procedural characteristics were recorded for each patient. The patients were categorized according to RV function at baseline as assessed by current guidelines, and a comparison of mortality rates up to 1 year was performed. RESULTS: Among 650 patients, 606 had adequate echocardiogram quality and 146 (24%) had RV dysfunction. There were significant differences between the 2 groups, as patients with RV dysfunction were younger (81±9 vs 84±7 years, P=.01) and were more likely to be male (65% vs 42%, P<.001). In addition, patients with RV dysfunction had higher rates of prior myocardial infarction (26% vs 16%, P=.02) and atrial fibrillation (51% vs 39%, P=.02). Echocardiographic parameters demonstrated higher rates of left ventricular ejection fraction <40% (40% vs 18%, P<.001), tricuspid regurgitation above moderate (16% vs 9%, P=.04), and higher pulmonary artery systolic pressure (50±17 vs 44±16 mm Hg, P<.001) among patients with severe AS and RV dysfunction compared with patients with normal RV function. Despite the unfavorable cardiac function, patients with severe AS undergoing TAVR have similar functional class (P=.22) and mortality rates at 1year (27% vs 23%, log-rank P=.45). CONCLUSIONS: Patients with severe AS and RV dysfunction have similar 1-year mortality and functional class after TAVR to patients with normal RV function. The presence of RV dysfunction does not correlate with outcome in patients with severe AS.

Outcome of implantation of a second self-expanding valve for the treatment of residual significant aortic regurgitation.

BACKGROUND: Residual aortic regurgitation (AR) following transcatheter aortic valve replacement (TAVR) is associated with adverse outcome. We sought to evaluate the efficacy and safety of second CoreValve (CV) implantation to treat residual AR following the initial CV deployment. METHODS AND RESULTS: TAVR patients treated with a second CV due to moderate and above residual AR were compared to single device implantation. Valvular function parameters were compared at baseline, post procedure, and 30 days. Among 172 CV TAVR patients, 11 required a second device (6%) due to significant residual AR. The main differences between the groups were higher rates of low ejection fraction in patients with 2 CV implanted and higher annular diameter (27 [29-25] vs. 25 [26-24] mm, P = 0.03), requiring a larger device. Although two patients in the two CV group had high initial implantation, low implantation was similar between the groups. A second CV achieved adequate reduction in residual AR in six patients (55%), while an additional four patients had moderate residual AR. Only one remained with moderate to severe AR after 30 days follow-up. There were no cases of peri-procedural stroke or mortality. CONCLUSIONS: Second implantation of self-expanding valve can successfully reduce residual significant AR following initial CV implantation and should be considered as therapeutic option for this population. © 2017 Wiley Periodicals, Inc.