Post-Procedure Monocyte Count Levels Predict Major Adverse Cardiovascular Events (MACE) Following Transcatheter Aortic Valve Implantation (TAVI) for Aortic Stenosis.

BACKGROUND: Aortic stenosis has recently been characterised as having an inflammatory aetiology, beyond the traditional degenerative model. Recruitment of monocytes has been associated with inflammation contributing to progression of calcific aortic-valve disease. Prior research has demonstrated that pre-procedure inflammatory biomarkers do not consistently discriminate poorer outcomes in those with aortic stenosis. It remains, however, unclear if postprocedure inflammatory biomarkers, which are influenced by intraprocedural pro-inflammatory insults, can predict major adverse cardiovascular events (MACE) post transcatheter aortic valve implantation (TAVI). METHOD: All patients with postprocedure monocyte levels undergoing transcatheter aortic valve implantation at The Alfred Hospital, Melbourne, Australia (2008-2019) were included. The highest monocyte count from postprocedure days 1 to 3 was used. Patients were divided into "high" or "low" postprocedure monocyte count groups using the Youden Index. The incidence of 30-day MACE a composite of stroke, acute myocardial infarction, and death) was then compared. RESULTS: In total, 472 patients were included (54% men, median age 84 years). Fourteen (14) patients (3%) suffered a 30-day MACE. Those with high postprocedure monocyte count were more likely to: be hypertensive (p=0.049); have a higher Society of Thoracic Surgeons risk score (p=0.032); and, undergo non-transfemoral access (p=0.018). A high (≥0.975) postprocedure monocyte count was significantly associated with 30-day MACE (odds ratio [OR] 1.16 for each 0.1 increase in monocyte, p=0.025). This association remained present on multivariable analysis adjusted for age, sex, Society of Thoracic Surgeons risk score, and self-expanding valve prosthesis type (OR 1.17, p=0.028). CONCLUSIONS: The association between postprocedure monocytosis and 30-day MACE suggests that minimising peri-procedural inflammatory insults may improve outcomes. This inexpensive and readily available biomarker may also aid in tailored risk stratification for patients.

Nano-Assembled Polyphosphazene Delivery System Enables Effective Intranasal Immunization with Nipah Virus Subunit Vaccine.

The ultimate vaccine against infections caused by Nipah virus should be capable of providing protection at the respiratory tract─the most probable port of entry for this pathogen. Intranasally delivered vaccines, which target nasal-associated lymphoid tissue and induce both systemic and mucosal immunity, are attractive candidates for enabling effective vaccination against this lethal disease. Herein, the water-soluble polyphosphazene delivery vehicle assembles into nanoscale supramolecular constructs with the soluble extracellular portion of the Hendra virus attachment glycoprotein─a promising subunit vaccine antigen against both Nipah and Hendra viruses. These supramolecular constructs signal through Toll-like receptor 7/8 and promote binding interactions with mucin─an important feature of effective mucosal adjuvants. High mass contrast of phosphorus-nitrogen backbone of the polymer enables a successful visualization of nanoconstructs in their vitrified state by cryogenic electron microscopy. Here, we characterize the self-assembly of polyphosphazene macromolecule with biologically relevant ligands by asymmetric flow field flow fractionation, dynamic light scattering, fluorescence spectrophotometry, and turbidimetric titration methods. Furthermore, a polyphosphazene-enabled intranasal Nipah vaccine candidate demonstrates the ability to induce immune responses in hamsters and shows superiority in inducing total IgG and neutralizing antibodies when benchmarked against the respective clinical stage alum adjuvanted vaccine. The results highlight the potential of polyphosphazene-enabled nanoassemblies in the development of intranasal vaccines.

Incidence, Predictors, and Outcomes of Nonhome Discharge Following Transcatheter Aortic Valve Implantation: A Multicenter Australian Experience-The NHD TAVI Study.

Patients who undergo transcatheter aortic valve implantation (TAVI) commonly experience nonhome discharge (NHD), a phenomenon associated with increased health care expenditure and possibly poorer outcomes. Despite its clinical relevance in TAVI, the incidence and predictors of NHD and its impact on the quality of life remain poorly characterized. Also unknown is the proportion of patients who undergo TAVI that require long-term residential care after initial NHD. Therefore, we aimed to address these questions using a large, multicenter Australian cohort. A total of 2,229 patients who underwent TAVI from 2010 to 2023 included in the Alfred-Cabrini-Epworth TAVI Registry were analyzed. The median age was 82 (interquartile range 78 to 86) years and 41% were women. A total of 257 patients (12%) were not discharged home after TAVI, with the incidence falling over time (R2 = 0.636, p <0.001). A multivariable logistic regression model for NHD prediction was developed with excellent calibration and discrimination (C-statistic = 0.835). The independent predictors of NHD were postprocedural stroke (adjusted odds ratio [aOR] 11.05), procedure at a private hospital (aOR 3.01), living alone (aOR 2.35), vascular access site complications (aOR 2.09), frailty (aOR 1.89), age >80 years (aOR 1.82), hypoalbuminemia (aOR 1.76), New York Heart Association III to IV (aOR 1.74), and hospital length of stay (aOR 1.13) (all p <0.05). NHD was not associated with mortality at 30 days and <1% of all patients required longer-term residential care. In conclusion, although common after TAVI, NHD does not predict short-term mortality, most patients successfully return home within 30 days, and when used appropriately, NHD may serve as a brief and effective method of optimizing functional status without compromising long-term independence.

Derivation and Validation of Thresholds Using Synthetic Data Methods for Single-Test Screening of Emergency Department Patients with Possible Acute Myocardial Infarction Using a Point-of-Care Troponin Assay.

BACKGROUND: Single-sample (screening) rule-out of acute myocardial infarction (AMI) with troponin requires derivation of a single-test screening threshold. In data sets with small event numbers, the lowest one or two concentrations of myocardial infarction (MI) patients dictate the threshold. This is not optimal. We aimed to demonstrate a process incorporating both real and synthetic data for deriving such thresholds using a novel pre-production high-precision point-of-care assay. METHODS: cTnI concentrations were measured from thawed plasma using the Troponin I Next (TnI-Nx) assay (i-STAT; Abbott) in adults on arrival to the emergency department with symptoms suggestive of AMI. The primary outcome was an AMI or cardiac death within 30 days. We used internal-external validation with synthetic data production based on clinical and demographic data, plus the measured TnI-Nx concentration, to derive and validate decision thresholds for TnI-Nx. The target low-risk threshold was a sensitivity of 99% and a high-risk threshold specificity of >95%. RESULTS: In total, 1356 patients were included, of whom 191 (14.1%) had the primary outcome. A total of 500 synthetic data sets were constructed. The mean low-risk threshold was determined to be 5 ng/L. This categorized 38% (95% CI, 6%-68%) to low-risk with a sensitivity of 99.0% (95% CI, 98.6%-99.5%) and a negative predictive value of 99.4% (95% CI, 97.6%-99.8%). A similarly derived high-risk threshold of 25 ng/L had a specificity of 95.0% (95% CI, 94.8%-95.1%) and a positive predictive value of 74.8% (95% CI, 71.5%-78.0%). CONCLUSIONS: With the TnI-Nx assay, we successfully demonstrated an approach using synthetic data generation to derive low-risk thresholds for safe and effective screening.

Comparative analysis of novel heat-treated retreatment file system on the removal of obturating material using nano-computed tomography.

Introduction: The aim of nonsurgical retreatment is to remove the previous filling material followed by chemo-mechanical preparation of the canal to achieve proper disinfection of the root canal system. This is then followed by re-obturation. This study evaluates the time taken to retrieve the gutta-percha and the quantity of remaining filling material after retreatment with two different file systems. The quantity of remaining filling material was assessed using nano-computed tomography (CT) due to its increased accuracy. Materials and Methods: Forty extracted single-rooted teeth were split into two groups at random and decoronated and obturated at a standard root length of 16 mm. Solite RS3 (SRS-3) Retreatment and ProTaper Universal Retreatment (PTUR) systems were used to retrieve the gutta-percha after a preoperative nano-CT scan. Postoperative nano-CT scan was taken and both the scans were superimposed to quantify the remaining filling material. The time taken to remove gutta-percha was measured using a stopwatch. The statistical analysis comparing the two groups was conducted using the independent t-test. Results: The quantitative analysis of remaining filling material using nano-CT showed no statistical difference between both the file systems used (P > 0.05). However, SRS-3 took significantly less time in the removal of gutta-percha (P < 0.05). Conclusion: Hence, we can conclude that there is no significant difference in the amount of remaining filling material between both the file systems. However, time taken to remove the gutta-percha was lesser in SRS-3 compared to PTUR file system.

Remineralization potential of strontium-doped nano-hydroxyapatite dentifrice and casein phosphopeptide-amorphous calcium phosphate cream on white spot lesions in enamel following orthodontic debonding - a randomized controlled trial.

Aim and Objective: This study was intended to compare and determine the potency of strontium-doped nano-hydroxyapatite paste against a topical cream containing casein phosphopeptide-amorphous calcium phosphate and a regular dentifrice for remineralization of white spot lesions of enamel following orthodontic debonding. Methods: Ninety individuals with white spot lesions on their enamel who visited the orthodontic department for de-bonding were selected for the research. Patients were randomly assigned to three distinct groups with each group consisting of 30 patients. Group 1 served as the control and received regular dentifrice, Group 2 received strontium-doped nano-hydroxyapatite paste, and Group 3 received casein phosphopeptide-amorphous calcium phosphate topical cream. Patients were instructed to locally apply a specified amount of the prescribed preparation twice daily for six weeks. The data were analysed using the statistical programme SPSS 22.0 (SPSS Inc., Chicago, IL, USA), and the level of significance had been set at p < 0.05. Results: Group 1 did not show any change in the enamel following the application of toothpaste. Both Group 2 and 3 demonstrated higher post-treatment scores, indicating effective remineralization potential (p < 0.001). However, Group 2 (strontium-doped nano-hydroxyapatite paste) displayed significantly greater remineralization capacity when compared to group 3 (casein phosphopeptide-amorphous calcium phosphate topical cream). Conclusion: Compared to conventional dentifrice and casein phosphopeptide-amorphous calcium phosphate paste, strontium-doped nano-hydroxyapatite preparation demonstrated greater enamel remineralization of the white spot lesions and favourable surface alterations in the enamel surface. strontium-doped nano-hydroxyapatite can be utilised safely and efficiently to treat early caries and remineralise white spot lesions on the enamel.

Acute Kidney Injury Following Transcatheter Aortic Valve Implantation-A Contemporary Perspective of Incidence, Predictors, and Outcomes.

BACKGROUND: Acute kidney injury (AKI) is a known complication following transcatheter aortic valve implantation (TAVI), associated with increased morbidity and mortality. Most of this data relates to higher-risk patients with early-generation TAVI valves. With TAVI now established as a safe and cost-effective procedure for low-risk patients, there is a distinct need for updated analysis. We aimed to assess the incidence, predictors, and outcomes of AKI in a contemporary cohort of TAVI patients, concurrently examining the role of temporal evolution on AKI. METHOD: A total of 2,564 patients undergoing TAVI from 2008-2023 included in the Alfred-Cabrini-Epworth (ACE) TAVI Registry were analysed. Patients were divided into AKI and no AKI groups. Outcomes were reported according to the Valve Academic Research Consortium-3 (VARC-3) criteria. RESULTS: Of 2,564 patients, median age 83 (78-87) years, 57.4% men and a median Society of Thoracic Surgeons score of 3.6 (2.4-5.5), 163 (6.4%) patients developed AKI with incidence falling from 9.7% between 2008-2014 to 6% between 2015-2023 (p=0.022). On multivariable analysis, independent predictors of AKI were male sex (adjusted odds ratio [aOR] 1.89, p=0.005), congestive cardiac failure (aOR 1.52, p=0.048), estimated glomerular filtration rate 30-59 (aOR: 2.79, p<0.001), estimated glomerular filtration rate <30 (aOR 8.65, p<0.001), non-femoral access (aOR 5.35, p<0.001), contrast volume (aOR 1.01, p<0.001), self-expanding valve (aOR 1.60, p=0.045), and bleeding (aOR 2.88, p=0.005). Acute kidney injury was an independent predictor of 30-day (aOR: 6.07, p<0.001) and 12-month (aOR: 3.01, p=0.002) mortality, an association that remained consistent when excluding TAVIs performed prior to 2015. CONCLUSIONS: Acute kidney injury remains a relatively common complication of TAVI, associated with significant morbidity and mortality even in less comorbid, contemporary practice patients.

Glucose and Psychosocial Outcomes 12 Months Following Transition from Multiple Daily Injections to Advanced Hybrid Closed Loop in Youth with Type 1 Diabetes and Suboptimal Glycemia.

Objective: To investigate 12-month glycemic and psychosocial changes following transition from multiple daily injections (MDI) to advanced hybrid closed-loop (AHCL) therapy in youth (aged 13-25 years) with type 1 diabetes and suboptimal glycemia (glycated hemoglobin [HbA1c] ≥8.5% [69 mmol/mol]). Research Design and Methods: Prospective, single arm, dual-center study in 20 participants. Extension phase outcomes reported after 12 months, including HbA1c, time in glycemic ranges, AHCL system performance, and psychosocial questionnaires assessing quality of life, diabetes treatment, and sleep. Results: After 12 months, 19 out of 20 participants continued to use AHCL. Average time-in-range 70-180 mg/dL (3.9-10.0 mmol/L) improved from 27.6% ± 13.2% to 62.5% ± 11.4%. This translated to an average 2.5 percentage-point (27.1 mmol/mol) improvement in HbA1c from 10.5% ± 2.1% (91.2 mmol/mol) at baseline to 8.0% ± 0.9% (64.1 mmol/mol) at 12 months. Psychosocial questionnaires and very high HbA1c at study entry indicated significant diabetes-associated burden for both individuals and parents. After 12 months, improvements were observed in general and diabetes-specific health-related quality of life, as well as in diabetes treatment satisfaction. Safety data were reassuring with a diabetic ketoacidosis rate of 0.15 per participant-year after 12 months of AHCL (compared to 0.25 per participant-year in the 12 months before the study). Conclusions: After 12 months of AHCL usage, this study highlights the potential for substantial and sustained glycemic and psychosocial improvements among individuals experiencing considerable diabetes burden and suboptimal glycemia, following their switch from MDI to AHCL.

Assessment of Occlusal Load Strength of Glass Ionomer Cement and Composite in Class V Cavities: An In-Vitro Study.

BACKGROUND:  Glass ionomer cement (GIC) is widely used in dentistry due to its chemical adhesion to dental tissues, biocompatibility, and anti-cariogenic potential but they have relatively weak mechanical properties. Resin composites have been widely regarded as the first choice for direct restorations but their polymerization shrinkage has remained a major problem. It has the potential to cause tooth debonding. The composite interface leads to postoperative sensitivity, secondary caries, enamel cracks, and microleakage. A restorative material's capacity to withstand occlusal stresses and support the remaining tooth structure depends on this property. Although class V restorations are predominantly done with GIC, this study was done to compare the strength of composite with the same. The GIC restore glass which is commonly used was tested against restofill composite. The main objective of conducting the study was to compare the compressive strength of the composite vs GIC in cervical cavities. So the aim of the study is to assess the occlusal load strength of GIC and composite in class V cavities using the universal testing machine. MATERIALS AND METHODS:  This study was employed as an in vitro study involving 20 natural central incisor teeth without any carious lesions. Class V cavity preparation was done and the selected teeth were divided into two groups of ten each. The cavities were filled with D Tech Restore GIC and composite restorations (restofill), respectively, polished, and then subjected to testing. An eccentric load was applied to the tooth structure using an Instron (Instron E3000 Electropuls, Instron, Norwood, United States) - Universal testing machine with a cross-head speed of 1mm per minute, and the stresses were further analyzed in the presence of an occlusal loading test using a stainless steel jig of 1mm diameter which led to the sectioning of the tooth buccolingually under the applied load. RESULTS:  An independent t-test was used to assess the results, and it was concluded that the results were statistically significant (p<0.05) at p=0.034. CONCLUSION:  Conclusively, the results suggested that the occlusal load strength of the composite is greater when compared to GIC.

Stroke reduction by cerebral embolic protection devices in transcatheter aortic valve implantation: a systematic review and Bayesian meta-analysis.

OBJECTIVES: The use of cerebral embolic protection (CEP) during transcatheter aortic valve implantation (TAVI) has been studied in several randomised trials. We aimed to perform a systematic review and Bayesian meta-analysis of randomised CEP trials, focusing on a clinically relevant reduction in disabling stroke. METHODS: A systematic search was applied to three electronic databases, including trials that randomised TAVI patients to CEP versus standard treatment. The primary outcome was the risk of disabling stroke. Outcomes were presented as relative risk (RR), absolute risk differences (ARDs), numbers needed to treat (NNTs) and the 95% credible intervals (CrIs). The minimal clinically important difference was determined at 1.1% ARD, per expert consensus (NNT 91). The principal Bayesian meta-analysis was performed under a vague prior, and secondary analyses were performed under two informed literature-based priors. RESULTS: Seven randomised studies were included for meta-analysis (n=3996: CEP n=2126, control n=1870). Under a vague prior, the estimated median RR of CEP use for disabling stroke was 0.56 (95% CrI 0.28 to 1.19, derived ARD 0.56% and NNT 179, I2=0%). Although the estimated posterior probability of any benefit was 94.4%, the probability of a clinically relevant effect was 0-0.1% under the vague and informed literature-based priors. Results were robust across multiple sensitivity analyses. CONCLUSION: There is a high probability of a beneficial CEP treatment effect, but this is unlikely to be clinically relevant. These findings suggest that future trials should focus on identifying TAVI patients with an increased baseline risk of stroke, and on the development of new generation devices. PROSPERO REGISTRATION NUMBER: CRD42023407006.

Pasteurella sp. associated with fatal septicaemia in six African elephants.

The sudden mortality of African elephants (Loxodonta africana) in Botswana and Zimbabwe in 2020 provoked considerable public interest and speculation. Poaching and malicious poisoning were excluded early on in the investigation. Other potential causes included environmental intoxication, infectious diseases, and increased habitat stress due to ongoing drought. Here we show evidence of the mortalities in Zimbabwe as fatal septicaemia associated with Bisgaard taxon 45, an unnamed close relative of Pasteurella multocida. We analyse elephant carcasses and environmental samples, and fail to find evidence of cyanobacterial or other intoxication. Post-mortem and histological findings suggest a bacterial septicaemia similar to haemorrhagic septicaemia caused by P. multocida. Biochemical tests and 16S rDNA analysis of six samples and genomic analysis of one sample confirm the presence of Bisgaard taxon 45. The genome sequence contains many of the canonical P. multocida virulence factors associated with a range of human and animal diseases, including the pmHAS gene for hyaluronidase associated with bovine haemorrhagic septicaemia. Our results demonstrate that Bisgaard taxon 45 is associated with a generalised, lethal infection and that African elephants are susceptible to opportunistically pathogenic Pasteurella species. This represents an important conservation concern for elephants in the largest remaining metapopulation of this endangered species.

Mechanical characterisation of commercial artificial skin models.

Understanding of the mechanical properties of skin is crucial in evaluating the performance of skin-interfacing medical devices. Artificial skin models (ASMs) have rapidly gained attention as they are able to overcome the challenges in ethically sourcing consistent and representative ex vivo animal or human tissue models. Although some ASMs have become commercialised, a thorough understanding of the mechanical properties of the skin models is crucial to ensure that they are suitable for the purpose of the study. In the present study, skin and fat layers of ASMs (Simulab®, LifeLike®, SynDaver® and Parafilm®) were mechanically characterised through hardness, needle insertion, tensile and compression testing. Different boundary constraint conditions (minimally and highly constrained) were investigated for needle insertion testing, while anisotropic properties of the skin models were investigated through different specimen orientations during tensile testing. Analysis of variance (ANOVA) tests were performed to compare the mechanical properties between the skin models. Properties of the skin models were compared against literature to determine the suitability of the skin models based on the material property of interest. All skin models offer relatively consistent mechanical performance, providing a solid basis for benchtop evaluation of skin-interfacing medical device performance. Through prioritising models with mechanical properties that are consistent with human skin data, and with limited variance, researchers can use the data presented here as a toolbox to select the most appropriate ASM for their particular application.

Coronary Artery Disease Risk Prediction in Patients With Severe Aortic Stenosis: Development and Validation of the Aortic Stenosis-Coronary Artery Disease (AS-CAD) Score.

Patients at a low risk of coronary artery disease (CAD) could be triaged to noninvasive coronary computed tomography angiogram instead of invasive coronary angiography, reducing health care costs and patient morbidity. Therefore, we aimed to develop a CAD risk prediction score to identify those who underwent transcatheter aortic valve implantation (TAVI) at a low risk of CAD. We enrolled 1,782 patients who underwent TAVI and randomized the patients to the derivation or validation cohort 2:1. The aortic stenosis-CAD (AS-CAD) score was developed using logistic regression, followed by separation into low- (score 0 to 5), intermediate- (6 to 10), or high-risk (>11) categories. The AS-CAD was validated initially through the k-fold cross-validation, followed by a separately held validation cohort. The average age of the cohort was 82 ± 7 years, and 41% (730 of 1,782) were female; 35% (630) had CAD. The male sex, previous percutaneous coronary intervention, stroke, peripheral arterial disease, diabetes, smoking status, left ventricular ejection fraction <50%, and right ventricular systolic pressure >35 mm Hg were all associated with an increased risk of CAD and were included in the final AS-CAD model (all p <0.03). Within the validation cohort, the AS-CAD score stratified those into low, intermediate, and high risk of CAD (p <0.001). Discrimination was good within the internal validation cohort, with a c-statistic of 0.79 (95% confidence interval 0.74 to 0.84), with similar power obtained using k-fold cross-validation (c-statistic 0.74 [95% confidence interval 0.70 to 0.77]). In conclusion, The AS-CAD score robustly identified those at a low risk of CAD in patients with severe AS. The use of AS-CAD in practice could avoid potential complications of invasive coronary angiogram by triaging low-risk patients to noninvasive coronary assessment using existing computed tomography data.

A Recombinant Chimeric Cedar Virus-Based Surrogate Neutralization Assay Platform for Pathogenic Henipaviruses.

The henipaviruses, Nipah virus (NiV), and Hendra virus (HeV) can cause fatal diseases in humans and animals, whereas Cedar virus is a nonpathogenic henipavirus. Here, using a recombinant Cedar virus (rCedV) reverse genetics platform, the fusion (F) and attachment (G) glycoprotein genes of rCedV were replaced with those of NiV-Bangladesh (NiV-B) or HeV, generating replication-competent chimeric viruses (rCedV-NiV-B and rCedV-HeV), both with and without green fluorescent protein (GFP) or luciferase protein genes. The rCedV chimeras induced a Type I interferon response and utilized only ephrin-B2 and ephrin-B3 as entry receptors compared to rCedV. The neutralizing potencies of well-characterized cross-reactive NiV/HeV F and G specific monoclonal antibodies against rCedV-NiV-B-GFP and rCedV-HeV-GFP highly correlated with measurements obtained using authentic NiV-B and HeV when tested in parallel by plaque reduction neutralization tests (PRNT). A rapid, high-throughput, and quantitative fluorescence reduction neutralization test (FRNT) using the GFP-encoding chimeras was established, and monoclonal antibody neutralization data derived by FRNT highly correlated with data derived by PRNT. The FRNT assay could also measure serum neutralization titers from henipavirus G glycoprotein immunized animals. These rCedV chimeras are an authentic henipavirus-based surrogate neutralization assay that is rapid, cost-effective, and can be utilized outside high containment.

30-Day Clinical Outcomes of a Self-Expanding Transcatheter Aortic Valve: The International PORTICO NG Study.

BACKGROUND: The self-expanding, intra-annular Navitor (Abbott Structural Heart) valve includes an outer cuff to reduce paravalvular leak (PVL) and large stent cells for future coronary access. OBJECTIVES: The purpose of the PORTICO NG (Evaluation of the Portico NG [Next Generation] Transcatheter Aortic Valve in High and Extreme Risk Patients With Symptomatic Severe Aortic Stenosis) study is to evaluate the safety and effectiveness of the Navitor valve in patients with symptomatic, severe aortic stenosis who are at high or extreme surgical risk. METHODS: PORTICO NG is a prospective, multicenter, global study with follow-up at 30 days, 1 year, and annually through 5 years. The primary endpoints are all-cause mortality and moderate or greater PVL at 30 days. Valve Academic Research Consortium-2 events and valve performance are assessed by an independent clinical events committee and echocardiographic core laboratory. RESULTS: A total of 260 subjects were treated at 26 clinical sites across Europe, Australia, and the United States between September 2019 and August 2022. The mean age was 83.4 ± 5.4 years, 57.3% were female, and the average Society of Thoracic Surgeons score was 3.9% ± 2.1%. At 30 days, the rate of all-cause mortality was 1.9%, and no subjects had moderate or greater PVL. The rate of disabling stroke was 1.9%, life-threatening bleeding was 3.8%, stage 3 acute kidney injury was 0.8%, major vascular complications were 4.2%, and new permanent pacemaker implantation was 19.0%. Hemodynamic performance included a mean gradient of 7.4 ± 3.5 mm Hg and an effective orifice area of 2.00 ± 0.47 cm2. CONCLUSIONS: The Navitor valve is safe and effective for the treatment of subjects with severe aortic stenosis who are at high or greater risk for surgery, which is supported by low rates of adverse events and PVL. (Evaluation of the Portico NG [Next Generation] Transcatheter Aortic Valve in High and Extreme Risk Patients With Symptomatic Severe Aortic Stenosis [PORTICO NG]; NCT04011722).

Thirty-day and one-year outcomes of the Navitor transcatheter heart valve in patients with aortic stenosis: the prospective, multicentre, global PORTICO NG Study.

BACKGROUND: The Navitor transcatheter heart valve (THV) is a self-expanding valve, with an intra-annular leaflet position and an outer cuff intended to reduce paravalvular leak (PVL). AIMS: The aim of the PORTICO NG Study is to assess the safety and performance of the Navitor THV in patients with symptomatic, severe aortic stenosis who are at high or extreme surgical risk. METHODS: PORTICO NG is a prospective, multicentre, global, single-arm, investigational study with follow-up at 30 days, 1 year, and annually up to 5 years. The primary endpoints are all-cause mortality and moderate or greater PVL at 30 days. Valve Academic Research Consortium-2 events and valve performance are assessed by an independent clinical events committee and echocardiographic core laboratory. RESULTS: A total of 120 high- or extreme-risk subjects (age 83.5±5.4 years; 58.3% female; Society of Thoracic Surgeons score 4.0±2.0%) were enrolled in the European conformity (CE) mark cohort. Procedural success was high at 97.5%. At 30 days, the rate of all-cause mortality was 0%, and no subjects had moderate or greater PVL. The rate of disabling stroke was 0.8%, life-threatening bleeding was 2.5%, stage 3 acute kidney injury 0%, major vascular complications 0.8%, and new pacemaker implantation 15.0%. At 1 year, the rates of all-cause mortality and disabling stroke were 4.2% and 0.8%, respectively. The rate of moderate PVL was 1.0% at 1 year. Haemodynamic performance with a mean gradient of 7.5±3.2 mmHg and effective orifice area of 1.9±0.4 cm2 was sustained up to 1 year. CONCLUSIONS: The PORTICO NG Study demonstrates low rates of adverse events and PVL up to 1 year in patients at high or extreme surgical risk, confirming the safety and efficacy of the Navitor THV system.

An in silico assessment on the potential of using saline infusion to overcome non-confluent coagulation zone during two-probe, no-touch bipolar radiofrequency ablation of liver cancer.

No-touch bipolar radiofrequency ablation (bRFA) is known to produce incomplete tumour ablation with a 'butterfly-shaped' coagulation zone when the interelectrode distance exceeds a certain threshold. Although non-confluent coagulation zone can be avoided by not implementing the no-touch mode, doing so exposes the patient to the risk of tumour track seeding. The present study investigates if prior infusion of saline into the tissue can overcome the issues of non-confluent or butterfly-shaped coagulation. A computational modelling approach based on the finite element method was carried out. A two-compartment model comprising the tumour that is surrounded by healthy liver tissue was developed. Three cases were considered; i) saline infusion into the tumour centre; ii) one-sided saline infusion outside the tumour; and iii) two-sided saline infusion outside the tumour. For each case, three different saline volumes were considered, i.e. 6, 14 and 22 ml. Saline concentration was set to 15% w/v. Numerical results showed that saline infusion into the tumour centre can overcome the butterfly-shaped coagulation only if the infusion volume is sufficient. On the other hand, one-sided infusion outside the tumour did not overcome this. Two-sided infusion outside the tumour produced confluent coagulation zone with the largest volume. Results obtained from the present study suggest that saline infusion, when carried out correctly, can be used to effectively eradicate liver cancer. This presents a practical solution to address non-confluent coagulation zone typical of that during two-probe bRFA treatment.

Impact of Advanced Hybrid Closed Loop on Youth With High-Risk Type 1 Diabetes Using Multiple Daily Injections.

OBJECTIVE: To evaluate glycemic outcomes in youth (aged 13-25 years) with type 1 diabetes and high-risk glycemic control (HbA1c ≥8.5% [69 mmol/mol]) on multiple daily injection (MDI) therapy after transitioning to advanced hybrid closed loop (AHCL) therapy. RESEARCH DESIGN AND METHODS: This prospective, 3-month, single-arm, dual-center study enrolled 20 participants, and all completed the study. RESULTS: HbA1c decreased from 10.5 ± 2.1% (91.2 ± 22.8 mmol/mol) at baseline to 7.6 ± 1.1% (59.7 ± 11.9 mmol/mol), and time spent in target range 70-180 mg/dL (3.9-10.0 mmol/L) increased from 27.6 ± 13.2% at baseline to 66.5 ± 9.8% after 3 months of AHCL. Two episodes of diabetic ketoacidosis attributed to infusion set failure occurred. CONCLUSIONS: AHCL has the potential to improve suboptimal glycemia in youth with type 1 diabetes previously on MDI therapy.

Long-Term Valve Durability in Patients Undergoing Transcatheter Aortic Valve Implantation.

AIMS: To evaluate the long-term incidence of structural valve deterioration (SVD) in patients who underwent transcatheter aortic valve implantation (TAVI). METHOD AND RESULTS: Between 2008 and 2018, 693 underwent TAVI at two centres. Four hundred and twenty-one (421) patients (mean age 83.6±6.0 yrs) survived for ≥2 years post TAVI and had at least two consecutive transthoracic echocardiographies (TTEs) with the latest TTE no less than 2 years after TAVI, and were therefore included in the analysis for SVD. Median follow-up was 4.7 (3.6-6.0) years and median echocardiography follow-up 3 (3.0-4.0) years. All-cause mortality was 30.9% (130) with a median time to death of 4.1 (3.0-5.6) years. The cumulative incidence of SVD increased from 1.7% (95% CI, 0.4-2.9) at 3 years to 3.5% (95% CI, 1.5-5.8) at 5 years and 4.7% (95% CI, 1.6-7.9) at 10 years. The overall median time to SVD was 3 (2-4) years. Twelve (12) patients demonstrated SVD stage 2, and 1 patient stage 3. No SVD required re-intervention. All other patients showed no significant changes in valve parameters over time. CONCLUSIONS: Structural valve deterioration is an uncommon event, occurring in 5% over a total follow-up of 10 years. Most patients show stable valve parameters. However, the analysis is limited by the loss of follow-up (owing to patient mortality), which renders extrapolation of the data to a younger patient population difficult.

A new species of Bregmaceros (Gadiformes: Bregmacerotidae) from the eastern Pacific Ocean, with comments on B. atlanticus and B. japonicus.

A new species of Bregmaceros is described based on a series of specimens from the eastern Pacific Ocean from near the Hawaiian Islands eastward to the California Current region. The new species bears considerable similarity in body shape and pigmentation to other overall darkly pigmented species with moderately high anal-fin counts (5159 in B. moseri) and modified prehaemal anal-fin pterygiophores (B. atlanticus and B. japonicus). The form and occurrence of these modified pterygiophores among Bregmaceros species is discussed. The new species is distinguished from B. atlanticus and B. japonicus and other undescribed forms in the historical literature commonly referred to Bregmaceros mcclellandi based on its high precaudal (prehaemal) vertebral counts (15 or 16 vs. 1315, typically 14) and associated elongation of the anterior portion of the body, and dark pigmentation concentrated dorsally on body and on head dorsal to nares anteriorly and operculum posteriorly but little or no pigment on lateral and ventral surfaces of head. The new species uniquely shares with these other species the modified prehaemal anal-fin pterygiophores and a lack of posterior bifurcation of the coelomic space otherwise present in the remaining species in the genus.