Studies of transcatheter pulmonary valve (TPV) replacement with the Melody valve have demonstrated good short-term outcomes, but there are no published long-term follow-up data.
The US ...Investigational Device Exemption trial prospectively enrolled 171 pediatric and adult patients (median age, 19 years) with right ventricular outflow tract conduit obstruction or regurgitation. The 148 patients who received and were discharged with a TPV were followed up annually according to a standardized protocol. During a median follow-up of 4.5 years (range, 0.4-7 years), 32 patients underwent right ventricular outflow tract reintervention for obstruction (n=27, with stent fracture in 22), endocarditis (n=3, 2 with stenosis and 1 with pulmonary regurgitation), or right ventricular dysfunction (n=2). Eleven patients had the TPV explanted as an initial or second reintervention. Five-year freedom from reintervention and explantation was 76±4% and 92±3%, respectively. A conduit prestent and lower discharge right ventricular outflow tract gradient were associated with longer freedom from reintervention. In the 113 patients who were alive and reintervention free, the follow-up gradient (median, 4.5 years after implantation) was unchanged from early post-TPV replacement, and all but 1 patient had mild or less pulmonary regurgitation. Almost all patients were in New York Heart Association class I or II. More severely impaired baseline spirometry was associated with a lower likelihood of improvement in exercise function after TPV replacement.
TPV replacement with the Melody valve provided good hemodynamic and clinical outcomes up to 7 years after implantation. Primary valve failure was rare. The main cause of TPV dysfunction was stenosis related to stent fracture, which was uncommon once prestenting became more widely adopted.
URL: http://www.clinicaltrials.gov. Unique identifier: NCT00740870.
Fish immunization has been carried out for over 50 years and is generally accepted as an effective method for preventing a wide range of bacterial and viral diseases. Vaccination efforts contribute ...to environmental, social, and economic sustainability in global aquaculture. Most licensed fish vaccines have traditionally been inactivated microorganisms that were formulated with adjuvants and delivered through immersion or injection routes. Live vaccines are more efficacious, as they mimic natural pathogen infection and generate a strong antibody response, thus having a greater potential to be administered via oral or immersion routes. Modern vaccine technology has targeted specific pathogen components, and vaccines developed using such approaches may include subunit, or recombinant, DNA/RNA particle vaccines. These advanced technologies have been developed globally and appear to induce greater levels of immunity than traditional fish vaccines. Advanced technologies have shown great promise for the future of aquaculture vaccines and will provide health benefits and enhanced economic potential for producers. This review describes the use of conventional aquaculture vaccines and provides an overview of current molecular approaches and strategies that are promising for new aquaculture vaccine development.
Transcatheter pulmonary valve placement is an emerging therapy for pulmonary regurgitation and right ventricular outflow tract obstruction in selected patients. The Melody valve was recently approved ...in the United States for placement in dysfunctional right ventricular outflow tract conduits.
From January 2007 to August 2009, 136 patients (median age, 19 years) underwent catheterization for intended Melody valve implantation at 5 centers. Implantation was attempted in 124 patients; in the other 12, transcatheter pulmonary valve placement was not attempted because of the risk of coronary artery compression (n=6) or other clinical or protocol contraindications. There was 1 death from intracranial hemorrhage after coronary artery dissection, and 1 valve was explanted after conduit rupture. The median peak right ventricular outflow tract gradient was 37 mm Hg before implantation and 12 mm Hg immediately after implantation. Before implantation, pulmonary regurgitation was moderate or severe in 92 patients (81% with data); no patient had more than mild pulmonary regurgitation early after implantation or during follow-up (>or=1 year in 65 patients). Freedom from diagnosis of stent fracture was 77.8+/-4.3% at 14 months. Freedom from Melody valve dysfunction or reintervention was 93.5+/-2.4% at 1 year. A higher right ventricular outflow tract gradient at discharge (P=0.003) and younger age (P=0.01) were associated with shorter freedom from dysfunction.
In this updated report from the multicenter US Melody valve trial, we demonstrated an ongoing high rate of procedural success and encouraging short-term valve function. All reinterventions in this series were for right ventricular outflow tract obstruction, highlighting the importance of patient selection, adequate relief of obstruction, and measures to prevent and manage stent fracture. Clinical Trial Registration- URL: http://www.clinicaltrials.gov. Unique identifier: NCT00740870.
A web-based survey was conducted of ergonomics practitioners holding certifications in the U.S., Canada, Great Britain, Australia, and New Zealand. The survey follows 12 years after an earlier ...initial survey reported by Dempsey et al. (2005). Approximately 1221 eligible participants were invited by e-mail to participate, and 405 surveys were included in the final analysis. The survey queried use of basic instruments relevant to ergonomic practice as well as more specific analytical tools such as observational techniques for assessing postural demands of work and instrumentation for direct measurement of such demands. Some ergonomic assessment methods appear to have increased in their overall use by U.S. ergonomists compared to 2005 data. This was observed for: RULA, REBA, Psychophysical Upper Extremity Data, Strain Index, and ACGIH TLV for Hand Activity Level. There is minimal evidence of increased overall use of direct measurement approaches in the U.S. There appear to be geographic differences between countries/continents in terms of use of various methods. The use of mobile device/smart phone “apps” by ergonomists was queried and these technologies presently appear to be in early adoption phase with 24–28% of practitioners reporting use of an app in their ergonomics practice.
Endocarditis has emerged as one of the most concerning adverse outcomes in patients with congenital anomalies involving the right ventricular outflow tract (RVOT) and prosthetic valves.
The aim of ...this study was to evaluate rates and potential risk factors for endocarditis after transcatheter pulmonary valve replacement in the prospective Melody valve trials.
All patients in whom a transcatheter pulmonary valve (TPV) was implanted in the RVOT as part of 3 prospective multicenter studies comprised the analytic cohort. The diagnosis of endocarditis and involvement of the TPV were determined by the implanting investigator.
A total of 309 patients underwent transcatheter pulmonary valve replacement (TPVR) and were discharged with a valve in place. The median follow-up duration was 5.1 years, and total observation until study exit was 1,660.3 patient-years. Endocarditis was diagnosed in 46 patients (median 3.1 years after TPVR), and a total of 35 patients were reported to have TPV-related endocarditis (34 at the initial diagnosis, 1 with a second episode). The annualized incidence rate of endocarditis was 3.1% per patient-year and of TPV-related endocarditis was 2.4% per patient-year. At 5 years post-TPVR, freedom from a diagnosis of endocarditis was 89% and freedom from TPV-related endocarditis was 92%. By multivariable analysis, age ≤12 years at implant (hazard ratio: 2.3; 95% confidence interval: 1.2 to 4.4; p = 0.011) and immediate post-implant peak gradient ≥15 mm Hg (2.7; 95% confidence interval: 1.4 to 4.9; p = 0.002) were associated with development of endocarditis and with development of TPV-related endocarditis (age ≤12 years: 2.8; 95% confidence interval: 1.3 to 5.7; p = 0.006; gradient ≥15 mm Hg: 2.6; 95% confidence interval: 1.3 to 5.2; p = 0.008).
Endocarditis is an important adverse outcome following TVPR in children and adults with post-operative congenital heart disease involving the RVOT. Ongoing efforts to understand, prevent, and optimize management of this complication are paramount in making the best use of TPV therapy. (Melody Transcatheter Pulmonary Valve TPV Study: Post Approval Study of the Original Investigational Device Exemption IDE Cohort; NCT00740870; Melody Transcatheter Pulmonary Valve Post-Approval Study; NCT01186692; and Melody Transcatheter Pulmonary Valve TPV Post-Market Surveillance Study; NCT00688571)
Display omitted
Objectives
Characterize the safety and effectiveness of the Amplatzer Piccolo Occluder for patent ductus arteriosus (PDA) closure.
Background
The presence of a hemodynamically significant PDA has ...been associated with an increased risk of morbidity and mortality in children born premature.
Methods
This was a single arm, prospective, multicenter, non‐randomized study to evaluate the Amplatzer Piccolo Occluder to treat PDA in patients ≥700 g. From June 2017 to February 2019, 200 patients were enrolled at nine centers, with 100 patients weighing ≤2 kg. Primary effectiveness endpoint was the rate of PDA closure at 6‐month follow‐up. Primary safety endpoint was the rate of major complications through 6 months. Secondary endpoint was rate of significant pulmonary or aortic obstruction through 6 months' follow‐up.
Results
The implant success rate was 95.5% (191/200) overall and 99% in patients ≤2 kg (99/100). The primary effectiveness endpoint was achieved in 99.4% of implanted patients. Four patients experienced a primary safety endpoint event (2 transfusions, 1 hemolysis, and 1 aortic obstruction). There were no branch pulmonary artery obstructions. Five patients, all ≤2 kg, were noted to have worsening of tricuspid regurgitation (TR) after the procedure. None of the TR incidences manifested clinically. The Amplatzer Piccolo Occluder received FDA approval in January 2019 and became the first device approved for PDA closure in patients ≥700 g.
Conclusions
This study supports the safety and effectiveness of the Amplatzer Piccolo Occluder, particularly in patients between 700 g and 2 kg where there is currently a significant unmet need in the United States. ClinicalTrials.gov identifier: NCT03055858.
Vaccines continue to play an enormous role in the progression of aquaculture industries worldwide. Though preventable diseases cause massive economic losses, injection-based vaccine delivery is ...cost-prohibitive or otherwise impractical for many producers. Most oral vaccines, which are much cheaper to administer, do not provide adequate protection relative to traditional injection or even immersion formulas. Research has focused on determining why there appears to be a lack of protection afforded by oral vaccines. Here, we review the basic immunological principles associated with oral vaccination before discussing the recent progress and current status of oral vaccine research. This knowledge is critical for the development and advancement of efficacious oral vaccines for the aquaculture industry.
The interplay of transcription factors and cis-regulatory elements (CREs) orchestrates the dynamic and diverse genetic programs that assemble the human central nervous system (CNS) during development ...and maintain its function throughout life. Genetic variation within CREs plays a central role in phenotypic variation in complex traits including the risk of developing disease. We took advantage of the retina, a well-characterized region of the CNS known to be affected by pathogenic variants in CREs, to establish a roadmap for characterizing regulatory variation in the human CNS. This comprehensive analysis of tissue-specific regulatory elements, transcription factor binding, and gene expression programs in three regions of the human visual system (retina, macula, and retinal pigment epithelium/choroid) reveals features of regulatory element evolution that shape tissue-specific gene expression programs and defines regulatory elements with the potential to contribute to Mendelian and complex disorders of human vision.
The Melody valve was developed to extend the useful life of previously implanted right ventricular outflow tract (RVOT) conduits or bioprosthetic pulmonary valves, while preserving RV function and ...reducing the lifetime burden of surgery for patients with complex congenital heart disease.
Enrollment for the US Investigational Device Exemption study of the Melody valve began in 2007. Extended follow-up was completed in 2020. The primary outcome was freedom from transcatheter pulmonary valve (TPV) dysfunction (freedom from reoperation, reintervention, moderate or severe pulmonary regurgitation, and/or mean RVOT gradient >40 mm Hg). Secondary end points included stent fracture, catheter reintervention, surgical conduit replacement, and death.
One hundred seventy-one subjects with RVOT conduit or bioprosthetic pulmonary valve dysfunction were enrolled. One hundred fifty underwent Melody TPV replacement. Median age was 19 years (Q1-Q3: 15-26). Median discharge mean RVOT Doppler gradient was 17 mm Hg (Q1-Q3: 12-22). The 149 patients implanted >24 hours were followed for a median of 8.4 years (Q1-Q3: 5.4-10.1). At 10 years, estimated freedom from mortality was 90%, from reoperation 79%, and from any reintervention 60%. Ten-year freedom from TPV dysfunction was 53% and was significantly shorter in children than in adults. Estimated freedom from TPV-related endocarditis was 81% at 10 years (95% CI, 69%-89%), with an annualized rate of 2.0% per patient-year.
Ten-year outcomes from the Melody Investigational Device Exemption trial affirm the benefits of Melody TPV replacement in the lifetime management of patients with RVOT conduits and bioprosthetic pulmonary valves by providing sustained symptomatic and hemodynamic improvement in the majority of patients. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT00740870.
Burbot (Lota lota) are an ideal candidate for cool or cold-water aquaculture and are gaining interest because of their high economic value, low temperature requirements, and fast growth rate. Limited ...information exists on the innate and adaptive immune systems of this species. This is partly due to the lack of species-specific tools to determine antibody responses following disease or vaccination or to characterize the immune response in general. An anti-IgM monoclonal antibody (mAb 27C) was developed and characterized via enzyme-linked immunosorbent assay (ELISA) and Western blot for species specificity, affinity to the heavy chain of burbot IgM, and cross-reactivity to other reagents used in the analysis. The 27C monoclonal antibody was further utilized to develop an ELISA protocol to measure the specific antibody response of burbot following exposure to two pathogenic strains of Aeromonas sp. (A141 and IR004). This ELISA confirmed that vaccinated burbot that survived the challenge with either strain developed statistically higher titers of anti-Aeromonas antibodies specific for the relative strain when compared to fish that were not vaccinated or challenged. Western blot analysis further demonstrated that burbot surviving challenge had serum IgM that recognized distinct antigens specific to the strain they were challenged with, A141 bound to antigens in the 50-250Kda range and IR004 bound to a distinct 150Kda antigen. Western blots further indicated that each strain shared antigenic regions regardless of experimental Aeromonas strain exposure. Finally, immunofluorescent staining confirmed that mAb 27C binds to membrane-bound IgM (presumably B cells) on burbot head kidney cells. Taken together, results from this study demonstrate that mAb 27C specifically recognized burbot IgM and will be an important tool to further characterize the adaptive and cellular immune responses of this fish species.
Display omitted
•Production of a monoclonal antibody (mAb27C), specific to the heavy chain of burbot IgM.•mAb 27C detects differences in Aeromonas sp. (strains A141 and IR004) antibody titers after exposure or vaccination.•mAb 27C detects immunogenic regions of Aeromonas sp. (strains A141 and IR004) via western blot.•mAb 27C detects IgM + cells via immunocytochemistry.
PDF
