Characterization of linezolid- and methicillin-resistant coagulase-negative staphylococci in a tertiary hospital in China.

BACKGROUND: Recently, linezolid-resistant staphylococci have become an emerging problem worldwide. Understanding the mechanisms of resistance, molecular epidemiology and transmission of linezolid-resistant CoNS in hospitals is very important. METHODS: The antimicrobial susceptibilities of all isolates were determined by the microdilution method. The resistance mechanisms and molecular characteristics of the strains were determined using whole-genome sequencing and PCR. RESULTS: All the strains were resistant to oxacillin and carried the mecA gene; 13 patients (36.1%) had prior linezolid exposure. Most S. epidermidis and S. hominis isolates were ST22 and ST1, respectively. MLST typing and evolutionary analysis indicated most linezolid-resistant CoNS strains were genetically related. In this study, we revealed that distinct CoNS strains have different mechanisms of linezolid resistance. Among ST22-type S. epidermidis, acquisition of the T2504A and C2534T mutations in the V domain of the 23 S rRNA gene, as well as mutations in the ribosomal proteins L3 (L101V, G152D, and D159Y) and L4 (N158S), were linked to the development of linezolid resistance. In S. cohnii isolates, cfr, S158Y and D159Y mutations in the ribosomal protein L3 were detected. Additionally, emergence of the G2576T mutation and the cfr gene were major causes of linezolid resistance in S. hominis isolates. The cfr gene, G2576T and C2104T mutations, M156T change in L3 protein, and I188S change in L4 protein were found in S. capitis isolates. CONCLUSION: The emergence of linezolid-resistant CoNS in the environment is concerning because it involves clonal dissemination and frequently coexists with various drug resistance mechanisms.

Applications of Carbon-Based Materials in Activated Peroxymonosulfate for the Degradation of Organic Pollutants: A Review.

In recent years, water pollution has posed a serious threat to aquatic organisms and humans. Advanced oxidation processes (AOPs) based on activated peroxymonosulfate (PMS) show high oxidation, good selectivity, wide pH range and no secondary pollution in the removal of organic pollutants in water. Carbon-based materials are emerging green catalysts that can effectively activate persulfates to generate radical and non-radical active species to degrade organic pollutants. Compared with transition metal catalysts, carbon-based materials are widely used in SR-AOPs because of their low cost, non-toxicity, acid and alkali resistance, large specific surface area, and scalable surface charge, which can be used for selective control of specific water pollutants. This paper mainly presents several carbon-based materials used to activate PMS, including raw carbon materials and modified carbon materials (heteroatom-doped and metal-doped), analyzes and summarizes the mechanism of activating PMS by carbon-based catalysts, and discusses the influencing factors (temperature, pH, PMS concentration, catalyst concentration, inorganic anions, inorganic cations and dissolved oxygen) in the activation process. Finally, the future challenges and prospects of carbon-based materials in water pollution control are also presented.

Rapid characterization of isotopic purity of deuterium-labeled organic compounds and monitoring of hydrogen-deuterium exchange reaction using electrospray ionization-high-resolution mass spectrometry.

RATIONALE: Deuterium-labeled organic compounds, reagents, and drugs are widely used in many scientific research fields. Isotopic purity as the feature parameter of deuterated compounds is of great importance. In this article, we used electrospray ionization with high-resolution mass spectrometry (ESI-HRMS) to study isotopic purity of deuterium-labeled organic compounds based on assigning and distinguishing the corresponding H/D (hydrogen-deuterium) isotopolog ions of deuterated compounds. METHODS: We systematically considered the specific requirements of accuracy and resolution of ESI-HRMS when measuring isotopic purity and demonstrated some actual cases using ESI-HRMS and ultraperformance liquid chromatography (UPLC)-HRMS. Meanwhile, ESI-HRMS/MS of deuterated compounds was performed to obtain more information on deuterium-labeled position characterization. RESULTS: Two isotopic purity calculation methods based on the relative abundance in ESI-HRMS and UPLC-HRMS of H/D isotopolog ions (D0 -Dn ) were compared, which gave consistent isotopic purity values and were in good agreement with the certified isotopic purity values. We further studied and monitored the H/D exchange reaction of ethyl 3-(4-bromophenyl)-3-oxopropanoate (EBPO) by evaluating the dynamic isotopic purity changes in EBPO-D2 in the H/D exchange reaction in situ. CONCLUSION: The isotopic purity characterization methods using ESI-HRMS discussed in this article have some outstanding advantages: rapid, highly sensitive, very low sample consumption (even below nanogram level), and deuterated solvent-free. Thus, this low-impact analytical method requires less time and is cost effective and might have good application potential for in-situ isotopic purity analysis and for monitoring the H/D exchange reactions.

Sea Urchin-like NiCo2O4 Catalyst Activated Peroxymonosulfate for Degradation of Phenol: Performance and Mechanism.

How to efficiently activate peroxymonosulfate (PMS) in a complex water matrix to degrade organic pollutants still needs greater efforts, and cobalt-based bimetallic nanomaterials are desirable catalysts. In this paper, sea urchin-like NiCo2O4 nanomaterials were successfully prepared and comprehensively characterized for their structural, morphological and chemical properties via techniques, such as X-ray diffraction (XRD), transmission electron microscopy (TEM), scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS), among others. The sea urchin-like NiCo2O4 nanomaterials exhibited remarkable catalytic performance in activating PMS to degrade phenol. Within the NiCo2O4/PMS system, the removal rate of phenol (50 mg L-1, 250 mL) reached 100% after 45 min, with a reaction rate constant k of 0.091 min-1, which was 1.4-times higher than that of the monometallic compound Co3O4/PMS system. The outstanding catalytic activity of sea urchin-like NiCo2O4 primarily arises from the synergistic effect between Ni and Co ions. Additionally, a comprehensive analysis of key parameters influencing the catalytic activity of the sea urchin-like NiCo2O4/PMS system, including reaction temperature, initial pH of solution, initial concentration, catalyst and PMS dosages and coexisting anions (HCO3-, Cl-, NO3- and humic acid), was conducted. Cycling experiments show that the material has good chemical stability. Electron paramagnetic resonance (EPR) and quenching experiments verified that both radical activation (SO4•-, •OH, O2•-) and nonradical activation (1O2) are present in the NiCo2O4/PMS system. Finally, the possible degradation pathways in the NiCo2O4/PMS system were proposed based on gas chromatography-mass spectrometry (GC-MS). Favorably, sea urchin-like NiCo2O4-activated PMS is a promising technology for environmental treatment and the remediation of phenol-induced water pollution problems.

Theoretical Calculations Facilitating Catalysis for Advanced Lithium-Sulfur Batteries.

Lithium-sulfur (Li-S) batteries have emerged as one of the most hopeful alternatives for energy storage systems. However, the commercialization of Li-S batteries is still confronted with enormous hurdles. The poor conductivity of sulfur cathodes induces sluggish redox kinetics. The shuttling of polysulfides incurs the heavy failure of electroactive substances. Tremendous efforts in experiments to seek efficient catalysts have achieved significant success. Unfortunately, the understanding of the underlying catalytic mechanisms is not very detailed due to the complicated multistep conversion reactions in Li-S batteries. In this review, we aim to give valuable insights into the connection between the catalyst activities and the structures based on theoretical calculations, which will lead the catalyst design towards high-performance Li-S batteries. This review first introduces the current advances and issues of Li-S batteries. Then we discuss the electronic structure calculations of catalysts. Besides, the relevant calculations of binding energies and Gibbs free energies are presented. Moreover, we discuss lithium-ion diffusion energy barriers and Li2S decomposition energy barriers. Finally, a Conclusions and Outlook section is provided in this review. It is found that calculations facilitate the understanding of the catalytic conversion mechanisms of sulfur species, accelerating the development of advanced catalysts for Li-S batteries.

TAVR in an XXXL annulus (1057 mm2 ) with type I bicuspid aortic valve.

We report the largest annulus (>1000 m2 ) treated with transcatheter aortic valve replacement to date. It highlights the unique challenges in planning, sizing, and deployment considerations in the setting of a very large and altered geometry of a bicuspid aortic valve.

Utilizing ambulatory electrocardiogram monitoring to reduce conduction related death after transcatheter aortic valve replacement.

OBJECTIVE: The purpose of this study is to assess the utility of ambulatory cardiac monitoring (ACM) in detecting delayed advanced conduction abnormalities (DACA) and associated 30-day mortality. BACKGROUND: DACA are well-known complications of TAVR and may be associated with post-discharge mortality within 30-days. METHODS: Between October 2019 and October 2020, TAVR patients who were discharged home without a permanent pacemaker (PPM) were monitored with an ACM device for 14-days. The incidence of DACA at follow up, mortality and readmission within 30-days were investigated. The risk of DACA was assessed in three patient categories based on a composite of their 12-lead electrocardiogram (ECG) data. Group I: Normal pre-TAVR, periprocedural, and discharge ECGs. Group II: Normal pre-TAVR and abnormal subsequent ECGs. Group III. Abnormal baseline and abnormal subsequent ECGs. RESULTS: Among 340 TAVR patients, 248 were discharged home with an ACM device. The overall incidence of DACA was 7% (n = 17), of whom 4% (n = 10) required a PPM. Mortality and readmission between discharge and 30 days was 0% and 8.3%, respectively. Stratification of patients identified 96 (38.7%) patients in Group I: 50 (20%) in Group II, and 102 (41%) in Group III. The incidence of DACA requiring a PPM was 0% in Group I, 4% (n = 2) in Group II, and 8.5% (n = 8) in Group III (p < 0.004). CONCLUSIONS: In TAVR patients who were discharged home with ACM, none died between discharge and 30-days. For those with normal baseline, perioperative and discharge ECG, there were no events of DACA at 14-days.

Sex Disparities in the Treatment of Aortic Stenosis and Related Outcomes: An Analysis of the National Inpatient Sample.

INTRODUCTION: The impact of transcatheter aortic valve replacement (TAVR) on sex disparities has not been well established. This study sought to examine the impact of sex on outcomes following aortic valve replacement (AVR) for aortic stenosis (AS) in the era of routine TAVR. METHODS: We performed a cross-sectional analysis of the National Inpatient Sample (2009-18) to study AS visits for all AVR and in-hospital outcomes as a function of sex. Survey estimation commands were used to provide national estimates. RESULTS: There were an estimated 431,344 surgical AVR (SAVR) and 189,137 TAVR inpatient visits. Mortality was higher in women after SAVR (3.8% ± 0.1 vs. 2.7% ± 0.07, p < 0.001) and TAVR (2.4% ± 0.1 vs. 1.7% ± 0.1, p < 0.001) compared to men. Female patients undergoing SAVR had higher rates of permanent pacemaker (PPM) implantation, stroke, and bleeding (5.9% ± 0.1 vs. 5% ± 0.1, 2.8% ± 0.1 vs. 2.3% ± 0.07, and 37.8% ± 0.8 vs. 29.8% ± 0.6; p < 0.001, respectively) but lower rates of acute kidney injury (AKI) (16.4% ± 0.3 vs. 20.3% ± 0.3, p < 0.001). Women undergoing TAVR had higher rates of stroke and bleeding (2.4% ± 0.1 vs. 1.6% ± 0.09 and 28.7% ± 0.6 vs. 22% ± 0.5; p < 0.001, respectively) but lower rates of PPM and AKI (9.5% ± 0.3 vs. 10.7% ± 0.2 and 11.3% ± 0.3 vs. 13.4% ± 0.3; p < 0.001, respectively). Compared with isolated SAVR, isolated TAVR was associated with lower mortality in women during 2016-18, both after multivariable adjustment (OR = 0.40; 95% CI, 0.27-0.60) and propensity matching (mean difference 0.66% ± 0.2); however, there was no difference in men. CONCLUSION: Although women continue to have higher in-hospital mortality following both TAVR and SAVR as compared to men, TAVR is associated with a lower in-hospital mortality in women compared to SAVR. Thus, TAVR may represent a potential intervention to narrow the sex-based disparities in the management of AS.

Contemporary trends and in-hospital outcomes of mechanical and bioprosthetic surgical aortic valve replacement in the United States.

INTRODUCTION: The choice between a mechanical versus a bioprosthetic valve in aortic valve replacement (AVR) is based on life expectancy, bleeding risk and comorbidities, since bioprosthetic AVR (bAVR) are associated with a more rapid structural deterioration compared to mechanical AVR (mAVR). The impact of widespread transcatheter valve replacements, on the decision to use bAVR versus mAVR, in the contemporary era and subsequent outcomes remain to be determined. METHODS: The National Inpatient database (2009-2018) was used to study trends in admissions for bAVR and mAVR and in-hospital mortality and outcomes over time. Survey estimation commands were used to determine weighted national estimates. RESULTS: There were 700,896 ± 18,285 inpatient visits for AVR with 70.1% (95% CI 69.2%-71.1%) and 29.9% (95% CI 28.9%-30.8%) visits for bAVR and mAVR, respectively. Those undergoing bAVR were significantly older (bAVR [69.8 years] vs. mAVR [62.7 years] p < .001]. The rates of mAVR decreased across all age groups during the study period (ptrend < .001), including patients ≤50 years (ptrend < .001). In-hospital mortality for mAVR recipients was higher, both after multivariable adjustment (OR 1.35 95% CI 1.26-1.45 p < .001) and propensity matching (mean difference 0.846% ± 0.19%). CONCLUSION: In the contemporary era, the utilization of mAVR has decreased across all age groups, including those younger than 50 years old. Although mAVR recipients were healthier with less comorbidities, inpatient mortality was higher after mAVR compared to bAVR. In addition to understanding causes for higher in-hospital mortality after mAVR, future research should focus on developing transcatheter valve replacement friendly bAVR.

Platelet glycoprotein VI-dependent thrombus stabilization is essential for the intraportal engraftment of pancreatic islets.

Platelet activation and thrombus formation have been implicated to be detrimental for intraportal pancreatic islet transplants. The platelet-specific collagen receptor glycoprotein VI (GPVI) plays a key role in thrombosis through cellular activation and the subsequent release of secondary mediators. In aggregometry and in a microfluidic dynamic assay system modeling flow in the portal vein, pancreatic islets promoted platelet aggregation and triggered thrombus formation, respectively. While platelet GPVI deficiency did not affect the initiation of these events, it was found to destabilize platelet aggregates and thrombi in this process. Interestingly, while no major difference was detected in early thrombus formation after intraportal islet transplantation, genetic GPVI deficiency or acute anti-GPVI treatment led to an inferior graft survival and function in both syngeneic mouse islet transplantation and xenogeneic human islet transplantation models. These results demonstrate that platelet GPVI signaling is indispensable in stable thrombus formation induced by pancreatic islets. GPVI deficiency resulted in thrombus destabilization and inferior islet engraftment indicating that thrombus formation is necessary for a successful intraportal islet transplantation in which platelets are active modulators.

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.

Integrating serum microRNAs and electronic health records improved the diagnosis of tuberculosis.

BACKGROUND: To verify the differential expression of miR-30c and miR-142-3p between tuberculosis patients and healthy controls and to investigate the performance of microRNA (miRNA) and subsequently models for the diagnosis of tuberculosis (TB). METHODS: We followed up 460 subjects suspected of TB, and finally enrolled 132 patients, including 60 TB patients, 24 non-TB disease controls (TB-DCs), and 48 healthy controls (HCs). The differential expression of miR-30c and miR-142-3p in serum samples of the TB patients, TB-DCs, and HCs were identified by reverse transcription-quantitative real-time PCR. Diagnostic models were developed by analyzing the characteristics of miRNA and electronic health records (EHRs). These models evaluated by the area under the curves (AUC) and calibration curves were presented as nomograms. RESULTS: There were differential expression of miR-30c and miR-142-3p between TB patients and HCs (p < 0.05). Individual miRNA has a limited diagnostic value for TB. However, diagnostic performance has been both significantly improved when we integrated miR-142-3p and ordinary EHRs to develop two models for the diagnosis of tuberculosis. The AUC of the model for distinguishing tuberculosis patients from healthy controls has increased from 0.75 (95% CI: 0.66-0.84) to 0.96 (95% CI: 0.92-0.99) and the model for distinguishing tuberculosis patients from non-TB disease controls has increased from 0.67 (95% CI: 0.55-0.79) to 0.94 (95% CI: 0.89-0.99). CONCLUSIONS: Integrating serum miR-142-3p and EHRs is a good strategy for improving TB diagnosis.

Discharge disposition of older patients undergoing trans-catheter aortic valve replacement and its impact on survival.

BACKGROUND: Patients undergoing transcatheter aortic valve replacement (TAVR) are likely to be discharged to a location other than home. We aimed to assess the association between discharge disposition after TAVR and patient survival at 1 year. METHODS: Patients admitted from home and survived till discharge after TAVR were divided into two groups based on discharge disposition (home discharge vs. non-home discharge). Pre-operative factors predicting the odds of not being discharged home were identified by using multivariable logistic regression analysis. Study patients were matched one-to-one via a propensity scoring method. Differences in procedural outcomes were compared. Survival of both unmatched and matched pairs was evaluated by using the Kaplan-Meier method with the Kleine-Moesch-Berger stratified log-rank test. RESULTS: Out of 1,160 TAVR patients, 851 were admitted from home and survived till discharge. The incidence non-home discharge was 19% (n = 159). Factors that were significantly associated with non-home discharge were older age, non-transfemoral approach, female sex, frailty status, history of chronic lung disease, pacemaker placement and insulin-dependent diabetes mellitus. One-to-one propensity score matching resulted in 141 patient pairs with similar age, operative risk, frailty and functional status. At 1-year follow-up, all-cause mortality rates were significantly higher in the non-home group than their home counterparts (18% vs. 3%, P = 0.006; stratified log rank test: P = 0.006). CONCLUSIONS: A considerable number of TAVR patients are discharged to a location other than home after the procedure. Not being discharged home after TAVR is associated with a high mortality risk at 1 year.

The impact of frailty status on clinical and functional outcomes after transcatheter aortic valve replacement in nonagenarians with severe aortic stenosis.

BACKGROUND: The impact of frailty status on TAVR outcomes in nonagenarians is unknown. The present study aims to investigate the impact of frailty status on procedural outcomes and overall survival in nonagenarians after TAVR. METHODS: A frailty score (FS) was derived by using preoperative grip strength, gait speed, serum albumin, and daily activities. Patients were divided into two groups: Frail (FS ≥ 3/4) and Non-Frail (FS <3/4). Health status was assessed using the 12-item Kansas City Cardiomyopathy Questionnaire (KCCQ). Baseline demographic and clinical characteristics were compared in both groups. The effect of frailty status on outcomes was investigated. Cox regression analyses were performed to determine predictors of overall all-cause mortality. Kaplan-Meier survival curves were used to estimate survival. RESULTS: Seventy-five patients >90 years underwent full assessment for frailty status. There was a significant improvement in overall health status of non-frail patients (mean difference: 11.03, P = 0.032). Unadjusted 30-day and 2-year mortality rates were higher in the frail group than the non-frail group. (14% vs. 2% P = 0.059; 31% vs. 9% P = 0.018). Kaplan-Meier estimated all-cause mortality to be significantly higher in the frail group (log-rank test; P = 0.042). Frailty status was independently associated with increased mortality (hazard ratio: 1.84, 95% C.I: 1.06-3.17; P = 0.028) after TAVR. CONCLUSION: Among nonagenarians selected to undergo TAVR for severe aortic stenosis, a considerable number are frail. Nonfrail patients report a significant improvement in overall health status in the short term. Worse frailty is strongly associated with diminished long-term survival. © 2017 Wiley Periodicals, Inc.

Impact of Tricuspid Valve Regurgitation on Early Outcomes after Transcatheter Aortic Valve Replacement.

BACKGROUND AND AIM OF THE STUDY: Tricuspid valve regurgitation (TR) is often not taken into consideration in the prognostication of patients undergoing transcatheter aortic valve replacement (TAVR). Accordingly, its impact on such patients remains relatively poorly defined. The study aim was to explore the effect of TR and parameters of right ventricular (RV) function on outcomes in patients undergoing TAVR. METHODS: Baseline demographic and echocardiographic data were collected for 460 consecutive patients undergoing TAVR at the authors' institution between 2012 and 2015. A retrospective analysis was performed to determine the association of TR with all-cause mortality in these patients. The primary endpoint was 30-day rate of all-cause mortality and/or hospital re-admission. RESULTS: Among 460 patients included in the study analysis there were 25 deaths and 40 re-admissions. Univariate analysis showed that a higher Society of Thoracic Surgeons (STS) score, severe preoperative mitral and tricuspid regurgitation were associated with statistically significant higher 30-day mortality and/or re-admission rates. On multivariate analysis, STS score (OR 1.07, 95% CI 1.012-1.126), moderate TR (OR 3.24, 95% CI 1.52-6.87) and severe TR (OR 2.5, 95% CI 1.04-6.04) were identified as significant independent predictors of all-cause mortality. CONCLUSIONS: The severity of TR is a strong independent parameter predictive of death at 30 days. Therefore, parameters of RV function such as TR should be incorporated into predictive models for patients undergoing TAVR.

Quantitative increase in frailty is associated with diminished survival after transcatheter aortic valve replacement.

BACKGROUND: The purpose of this study is to assess the impact of frailty index comprised of commonly used frailty metrics on outcomes following transcatheter aortic valve replacement (TAVR) outcomes, including mortality, length of stay, and discharge destination. METHODS AND RESULTS: Retrospective data collection was performed for 342 consecutive patients who underwent TAVR at a single center from May 15, 2012, to September 17, 2015. Frailty index score was calculated using 15-ft walk test, Katz activities of daily living, preoperative serum albumin, and dominant handgrip strength. Patients were given a frailty score from 0/4 to 4/4, with higher scores indicating greater levels of frailty. There were 27 patients (8%) in 0/4, 82 patients (24%) in 1/4, 129 patients (38%) in 2/4, 73 patients (21%) in 3/4, and 31 patients (9%) in 4/4 frailty group. Multivariate cox, logistic, and linear regression analyses showed that patients with frailty score of 3/4 or 4/4 had increased all-cause mortality (P = .015 and P < .001) and were more likely to be discharged to an acute care facility (P = .083 and P = .001). 4/4 frail patients had increased post-operative length of stay (P = .014) when compared to less frail patients. Individual components of the frailty score were also independent predictors of all-cause mortality. Median survival in 4/4 frail patients was 7 months. CONCLUSIONS: Frailty index comprised of commonly used frailty metrics and its components are independent predictors of poor post-TAVR outcomes. There is a stepwise increase in mortality and post-TAVR length of stay with increasing frailty with dismal prognosis in extremely frail patients.

Phase, microstructure and hydrogen storage properties of Mg-Ni materials synthesized from metal nanoparticles.

After Mg and Ni nanoparticles were fabricated by hydrogen plasma metal reaction, Mg-rich MgxNi100₋x(75 < x < 90) materials were synthesized from these metal nanoparticles to study the synergistic effects for hydrogen storage in these samples to show both good kinetics and high capacity. These MgxNi100₋x materials may absorb hydrogen with a capacity of around 3.3-5.1 wt% in 1 min at 573 K. The Mg90Ni10 sample shows a hydrogen capacity of 6.1 wt%. The significant kinetic enhancement is thought to be due to the unique nanostructure from the special synthesis route, the catalytic effect of the Mg2Ni nano phase, and the synergistic effects between the Mg2Ni and Mg phases in the materials. An interesting phenomenon which has never been reported before was observed during pressure composition isotherm (PCT) measurements. One steep step in the absorption process and two obviously separated steps in the desorption process during PCT measurements of Mg80Ni20 and Mg90Ni10 samples were observed and a possible reason from the kinetic performance of the Mg2Ni and Mg phases in absorption and desorption processes was explained. These MgxNi100₋x materials synthesized from Mg and Ni nanoparticles show high capacity and good kinetics, which makes these materials very promising candidates for thermal storage or energy storage and utilization for renewable power.

A prognostic signature established based on genes related to tumor microenvironment for patients with hepatocellular carcinoma.

BACKGROUND: Complex cellular signaling network in the tumor microenvironment (TME) could serve as an indicator for the prognostic classification of hepatocellular carcinoma (HCC) patients. METHODS: Univariate Cox regression analysis was performed to screen prognosis-related TME-related genes (TRGs), based on which HCC samples were clustered by running non-negative matrix factorization (NMF) algorithm. Furthermore, the correlation between different molecular HCC subtypes and immune cell infiltration level was analyzed. Finally, a risk score (RS) model was established by LASSO and Cox regression analyses (CRA) using these TRGs. Functional enrichment analysis was performed using gene set enrichment analysis (GSEA). RESULTS: HCC patients were divided into three molecular subtypes (C1, C2, and C3) based on 704 prognosis-related TRGs. HCC subtype C1 had significantly better OS than C2 and C3. We selected 13 TRGs to construct the RS model. Univariate and multivariate CRA showed that the RS could independently predict patients' prognosis. A nomogram integrating the RS and clinicopathologic features of the patients was further created. We also validated the reliability of the model according to the area under the receiver operating characteristic (ROC) curve value, concordance index (C-index), and decision curve analysis. The current findings demonstrated that the RS was significantly correlated with CD8+ T cells, monocytic lineage, and myeloid dendritic cells. CONCLUSION: This study provided TRGs to help classify patients with HCC and predict their prognoses, contributing to personalized treatments for patients with HCC.

Single-cell data revealed exhaustion of characteristic NK cell subpopulations and T cell subpopulations in hepatocellular carcinoma.

BACKGROUND: The treatment and prognosis of patients with advanced hepatocellular carcinoma (HCC) have been a major medical challenge. Unraveling the landscape of tumor immune infiltrating cells (TIICs) in the immune microenvironment of HCC is of great significance to probe the molecular mechanisms. METHODS: Based on single-cell data of HCC, the cell landscape was revealed from the perspective of TIICs. Special cell subpopulations were determined by the expression levels of marker genes. Differential expression analysis was conducted. The activity of each subpopulation was determined based on the highly expressed genes. CTLA4+ T-cell subpopulations affecting the prognosis of HCC were determined based on survival analysis. A single-cell regulatory network inference and clustering analysis was also performed to determine the transcription factor regulatory networks in the CTLA4+ T cell subpopulations. RESULTS: 10 cell types were identified and NK cells and T cells showed high abundance in tumor tissues. Two NK cells subpopulations were present, FGFBP2+ NK cells, B3GNT7+ NK cells. Four T cells subpopulations were present, LAG3+ T cells, CTLA4+ T cells, RCAN3+ T cells, and HPGDS+ Th2 cells. FGFBP2+ NK cells, and CTLA4+ T cells were the exhaustive subpopulation. High CTLA4+ T cells contributed to poor prognostic outcomes and promoted tumor progression. Finally, a network of transcription factors regulated by NR3C1, STAT1, and STAT3, which were activated, was present in CTLA4+ T cells. CONCLUSION: CTLA4+ T cell subsets in HCC exhibited functional exhaustion characteristics that probably inhibited T cell function through a transcription factor network dominated by NR3C1, STAT1, and STAT3.

Bridging the Gap: Pancreas Tissue Slices From Organ and Tissue Donors for the Study of Diabetes Pathogenesis.

Over the last two decades, increased availability of human pancreatic tissues has allowed for major expansions in our understanding of islet biology in health and disease. Indeed, studies of fixed and frozen pancreatic tissues, as well as efforts using viable isolated islets obtained from organ donors, have provided significant insights toward our understanding of diabetes. However, the procedures associated with islet isolation result in distressed cells that have been removed from any surrounding influence. The pancreas tissue slice technology was developed as an in situ approach to overcome certain limitations associated with studies on isolated islets or fixed tissue. In this Perspective, we discuss the value of this novel platform and review how pancreas tissue slices, within a short time, have been integrated in numerous studies of rodent and human islet research. We show that pancreas tissue slices allow for investigations in a less perturbed organ tissue environment, ranging from cellular processes, over peri-islet modulations, to tissue interactions. Finally, we discuss the considerations and limitations of this technology in its future applications. We believe the pancreas tissue slices will help bridge the gap between studies on isolated islets and cells to the systemic conditions by providing new insight into physiological and pathophysiological processes at the organ level. ARTICLE HIGHLIGHTS: Human pancreas tissue slices represent a novel platform to study human islet biology in close to physiological conditions. Complementary to established technologies, such as isolated islets, single cells, and histological sections, pancreas tissue slices help bridge our understanding of islet physiology and pathophysiology from single cell to intact organ. Diverse sources of viable human pancreas tissue, each with distinct characteristics to be considered, are available to use in tissue slices for the study of diabetes pathogenesis.