The adaptability of the Pulsta valve to the diverse main pulmonary artery shape of native right ventricular outflow tract disease.

BACKGROUND: Pulsta valve is increasingly used for percutaneous pulmonary valve implantation (PPVI) in patients with a large native right ventricular outflow tract (RVOT). This study aims to elucidate the outcomes of Pulsta valve implantation within the native RVOT and assess its adaptability to various native main pulmonary artery (PA) anatomies. METHODS: A multicenter retrospective study included 182 patients with moderate to severe pulmonary regurgitation in the native RVOT who underwent PPVI with Pulsta valves® between February 2016 and August 2023 at five Korean and Taiwanese tertiary referral centers. RESULTS: Pulsta valve implantation was successful in 179 out of 182 patients (98.4%) with an average age of 26.7 ± 11.0 years. The median follow-up duration was 29 months. Baseline assessments revealed enlarged right ventricle (RV) volume (mean indexed RV end-diastolic volume: 163.1 (interquartile range, IQR: 152.0-180.3 mL/m²), which significantly decreased to 123.6(IQR: 106.6-137.5 mL/m2  after 1 year. The main PA types were classified as pyramidal (3.8%), straight (38.5%), reverse pyramidal (13.2%), convex (26.4%), and concave (18.1%) shapes. Pulsta valve placement was adapted, with distal main PA for pyramidal shapes and proximal or mid-PA for reverse pyramidal shapes. Two patients experienced Pulsta valve embolization to RV, requiring surgical removal, and one patient encountered valve migration to the distal main PA, necessitating surgical fixation. CONCLUSIONS: Customized valve insertion sites are pivotal in self-expandable PPVI considering diverse native RVOT shape. The rather soft and compact structure of the Pulsta valve has characteristics to are adaptable to diverse native RVOT geometries.

Intravenous immunoglobulin resistance in Kawasaki disease patients: prediction using clinical data.

BACKGROUND: About 10-20% of Kawasaki disease (KD) patients are resistant to the initial infusion of intravenous immunoglobin (IVIG). The aim of this study was to assess whether IVIG resistance in KD patients could be predicted using standard clinical and laboratory features. METHODS: Data were from two cohorts: a Korean cohort of 7101 KD patients from 2015 to 2017 and a cohort of 649 KD patients from San Diego enrolled from 1998 to 2021. Features included laboratory values, the worst Z-score from the initial echocardiogram or during hospitalization, and the five clinical KD signs at presentation. RESULTS: Five machine learning models achieved a maximum median AUC of 0.711 [IQR: 0.706-0.72] in the Korean cohort and 0.696 [IQR: 0.609-0.722] in the San Diego cohort during stratified 10-fold cross-validation using significant laboratory features identified from univariate analysis. Adding the Z-score, KD clinical signs, or both did not considerably improve the median AUC in either cohort. CONCLUSIONS: Using commonly measured clinical laboratory data alone or in conjunction with echocardiographic findings and clinical features is not sufficient to predict IVIG resistance. Further attempts to predict IVIG resistance will need to incorporate additional data such as transcriptomics, proteomics, and genetics to achieve meaningful predictive utility. IMPACT: We demonstrated that laboratory, echocardiographic, and clinical findings cannot predict intravenous immunoglobin (IVIG) resistance to a clinically meaningful extent using machine learning in a homogenous Asian or ethnically diverse population of patients with Kawasaki disease (KD). Visualizing these features using uniform manifold approximation and projection (UMAP) is an important step to evaluate predictive utility in a qualitative manner. Further attempts to predict IVIG resistance in KD patients will need to incorporate novel biomarkers or other specialized features such as genetic differences or transcriptomics to be clinically useful.

Risk Factors for Coronary Artery Complications After Prosthetic Pulmonary Valve Implantation in Patients With Congenital Heart Disease.

BACKGROUND: Coronary artery complications (CACs) in patients who undergoing prosthetic pulmonary valve implantation for congenital heart disease can lead to fetal outcomes. However, the incidence of and risk factors for CACs in these patients remain unknown.Methods and Results: A retrospective cohort study was conducted on patients who underwent cardiac computed tomography or invasive coronary angiography after prosthetic pulmonary valve implantation at Seoul National University Hospital from June 1986 to May 2021. Among 341 patients, 25 (7.3%) were identified with CACs, and 2 of them died. Among the patients with CACs, congenital coronary anomalies and an interarterial course of the coronary artery were identified in 11 (44%) and 18 (72%) patients, respectively. Interarterial and intramural courses of the coronary artery were associated with a 4.4- and 10.6-fold increased risk of CACs, respectively. Among patients with tetralogy of Fallot and pulmonary atresia, the aortic root was rotated further clockwise in patients with coronary artery compression compared to those without it (mean [±SD] 128.0±19.9° vs. 113.5±23.7°; P=0.024). The cut-off rotation angle of the aorta for predicting the occurrence of coronary artery compression was 133°. CONCLUSIONS: Perioperative coronary artery evaluation and prevention of CACs are required in patients undergoing prosthetic pulmonary valve implantation, particularly in those with coronary artery anomalies or severe clockwise rotation of the aortic root.

Isosorbide, a versatile green chemical: Elucidating its ADME properties for safe use.

Isosorbide, an environmentally friendly and renewable substance, finds extensive application in diverse fields, such as a bisphenol A substitute, polymers, functional materials, organic solvents, fuels, and pharmaceuticals. Despite its increasing interest and widespread usage, there remains a notable absence of available reports regarding its absorption, distribution, metabolism, and excretion (ADME) properties. This study endeavors to investigate the ADME characteristics of isosorbide in rats. Isosorbide levels in biological samples were quantified based on the analytical method using gas chromatography-mass spectrometry (GC-MS). Following administration, isosorbide exhibited rapid absorption and elimination, with a bioavailability of 96.1%. The metabolic stability assay indicated that isosorbide remained stable during metabolism. The majority of absorbed isosorbide was promptly excreted, with urinary excretion as the primary route. This study furnishes valuable insights into the ADME of isosorbide, contributing to its safety assessment and fostering its continued application across various domains.

Newly Developed Sex-Specific Z Score Model for Coronary Artery Diameter in a Pediatric Population.

BACKGROUND: This study aimed to generate a Z score calculation model for coronary artery diameter of normal children and adolescents to be adopted as the standard calculation method with consensus in clinical practice. METHODS: This study was a retrospective, multicenter study that collected data from multiple institutions across South Korea. Data were analyzed to determine the model that best fit the relationship between the diameter of coronary arteries and independent demographic parameters. Linear, power, logarithmic, exponential, and square root polynomial models were tested for best fit. RESULTS: Data of 2,030 subjects were collected from 16 institutions. Separate calculation models for each sex were developed because the impact of demographic variables on the diameter of coronary arteries differs according to sex. The final model was the polynomial formula with an exponential relationship between the diameter of coronary arteries and body surface area using the DuBois formula. CONCLUSION: A new coronary artery diameter Z score model was developed and is anticipated to be applicable in clinical practice. The new model will help establish a consensus-based Z score model.

Computed Tomography Measurement of the Aorta in Midaortic Syndrome in Children and Adolescents and Their Clinical Manifestations and Outcomes.

Midaortic syndrome (MAS) presents challenges in diagnosis due to the absence of well-defined diagnostic criteria in pediatric patients. This retrospective study aimed to aid in the diagnosis of MAS by employing computed tomography (CT) to measure the z-score of the aorta as well as to identify and understand its clinical features. CT images, echocardiography findings, and medical records of 17 patients diagnosed with MAS between 1997 and 2023 were reviewed, and z-scores were calculated. Aortic size on follow-up CT, blood pressure, and left ventricular function and hypertrophy at the last follow-up were analyzed, and possible prognostic factors were examined. Except for one patient, all individuals exhibited a z-score below - 2 at the level corresponding to stenosis. Left ventricular dysfunction occurred more frequently in patients aged < 5 years (p = 0.024). Patients with idiopathic MAS showed a better prognosis in terms of blood pressure and follow-up aortic size (p = 0.051 and 0.048, respectively). CT-measured aortic z-scores may be useful for the diagnosis and follow-up of MAS.

Genetically Stable and Scalable Nanoengineering of Human Primary T Cells via Cell Mechanoporation.

Effective tumor regression has been observed with chimeric antigen receptor (CAR) T cells; however, the development of an affordable, safe, and effective CAR-T cell treatment remains a challenge. One of the major obstacles is that the suboptimal genetic modification of T cells reduces their yield and antitumor activity, necessitating the development of a next-generation T cell engineering approach. In this study, we developed a nonviral T cell nanoengineering system that allows highly efficient delivery of diverse functional nanomaterials into primary human T cells in a genetically stable and scalable manner. Our platform leverages the unique cell deformation and restoration process induced by the intrinsic inertial flow in a microchannel to create nanopores in the cellular membrane for macromolecule internalization, leading to effective transfection with high scalability and viability. The proposed approach demonstrates considerable potential as a practical alternative technique for improving the current CAR-T cell manufacturing process.

Sex Differences in Sarcopenia in Patients Undergoing Total Knee Arthroplasty for Advanced Knee Osteoarthritis.

Background and Objectives: The purpose of this study was to compare sex differences in the incidence of sarcopenia, demographic characteristics, and preoperative sarcopenic parameters in patients undergoing TKA for advanced knee osteoarthritis (OA). Moreover, we sought to compare patient-reported outcome measures (PROMs) and the predisposing factors after TKA in patients with sarcopenia by sex through subgroup analysis. Materials and Methods: From May 2020 to September 2022, a total of 892 patients who were evaluable for sarcopenia before primary TKA were enrolled. Sarcopenia was defined according to the Asian Working Group for Sarcopenia 2019 criteria. Patients were assessed according to the presence or absence of sarcopenia. After a two-to-one matched-pair analysis for subgroup analysis, 21 knees in men were matched with a corresponding number of knees in women (42), resulting in a total of 63 knees. PROMs were investigated using the Knee Injury and Osteoarthritis Outcome Score, Western Ontario and McMaster Universities Osteoarthritis Index, and the Short Form-12 physical and mental component summary scores. Moreover, the postoperative complications and predisposing factors for male sarcopenia were investigated. Results: The prevalence of sarcopenia was 10.9% (97/892), and the prevalence was higher in men (19.6%, 21/107) than in women (9.7%, 76/785). In subgroup analyses, male patients had significantly inferior PROMs up to 12 months after index surgery. Moreover, there was no significant difference in the systemic complications between the two groups. Multivariate binary logistic regression analysis indicated that alcohol consumption, smoking, and higher modified Charlson Comorbidity Index (mCCI) were predisposing factors for male patients with sarcopenia. The prevalence of sarcopenia was higher in male patients undergoing primary TKA. Conclusions: When compared with the propensity-matched female group, male patients had inferior PROMs up to 12 months postoperatively. Alcohol consumption, current smoker status, and higher mCCI were predisposing factors for sarcopenia in male patients with advanced knee OA.

Harnessing Oncolytic Extracellular Vesicles for Tumor Cell-Preferential Cytoplasmic Delivery of Misfolded Proteins for Cancer Immunotherapy.

In this study, extracellular vesicles (EVs) are reimagined as more than just a cellular waste disposal system and are repurposed for cancer immunotherapy. Potent oncolytic EVs (bRSVF-EVs) loaded with misfolded proteins (MPs) are engineered, which are typically considered cellular debris. By impairing lysosomal function using bafilomycin A1 and expressing the respiratory syncytial virus F protein, a viral fusogen, MPs are successfully loaded into the EVs expressing RSVF. bRSVF-EVs preferentially transplant a xenogeneic antigen onto cancer cell membranes in a nucleolin-dependent manner, triggering an innate immune response. Furthermore, bRSVF-EV-mediated direct delivery of MPs into the cancer cell cytoplasm initiates endoplasmic reticulum stress and immunogenic cell death (ICD). This mechanism of action leads to substantial antitumor immune responses in murine tumor models. Importantly, when combined with PD-1 blockade, bRSVF-EV treatment elicits robust antitumor immunity, resulting in prolonged survival and complete remission in some cases. Overall, the findings demonstrate that utilizing tumor-targeting oncolytic EVs for direct cytoplasmic delivery of MPs to induce ICD in cancer cells represents a promising approach for enhancing durable antitumor immunity.

Cardiovascular Characteristics and Progressions of Hypertrophic Cardiomyopathy and Pulmonary Stenosis in RASopathy Syndrome in the Genomic Era.

INTRODUCTION: To investigate cardiovascular characteristics and progressions of hypertrophic cardiomyopathy (HCM) and pulmonary stenosis (PS) and determine whether any genotype-phenotype correlations exist in patients with gene-confirmed RASopathy syndrome. STUDY DESIGN: Eighty patients (male, 55%) confirmed as having RASopathy syndrome by genetic testing at a single tertiary center were enrolled. Subjects' medical and echocardiography records were reviewed and the changes in the z scores of left ventricular wall thickness (LVWT) and the degree of PS over time were examined during follow-up of 5.7 ± 3.1 and 7.5 ± 5.2 years, respectively. RESULTS: The most common RASopathy gene identified was PTPN11 (56%), followed by RAF1 (10%). Eighty-five percent of patients had cardiovascular diseases, wherein 42% had HCM, and 38% PS. Mean maximal LVWT z score on the initial echocardiography (mean age 5.0 ± 6.0 years) was 3.4 ± 1.3 (median 2.8, range 2.1-6.6) in the HCM group. Overall, the maximal LVWT increased with time, especially in the HCM group (z = 3.4 ± 1.3 to 3.7 ± 1.6, P = .008) and RAF1-variant group (z = 3.7 ± 1.7 to 4.6 ± 1.8, P = .031). Five patients newly developed HCM during the study period. Genotype-phenotype correlation was significant for HCM (P = .002); 31% of patients with PTPN11 and 88% with RAF1 variants had HCM. PS did not progress in this study cohort. CONCLUSIONS: In this study, progression of ventricular hypertrophy was seen in a significant number of patients with genotype correlation. Thus, long-term follow up of cardiovascular problems in patients with RASopathy is necessary.

Visible to near-infrared single pixel microspectrometer using electrothermal MEMS grating.

Compact spectrometers facilitate non-destructive and point-of-care spectral analysis. Here we report a single-pixel microspectrometer (SPM) for visible to near-infrared (VIS-NIR) spectroscopy using MEMS diffraction grating. The SPM consists of slits, electrothermally rotating diffraction grating, spherical mirror, and photodiode. The spherical mirror collimates an incident beam and focuses the beam on the exit slit. The photodiode detects spectral signals dispersed by electrothermally rotating diffraction grating. The SPM was fully packaged within 1.7 cm3 and provides a spectral response range of 405 nm to 810 nm with an average 2.2 nm spectral resolution. This optical module provides an opportunity for diverse mobile spectroscopic applications such as healthcare monitoring, product screening, or non-destructive inspection.

Long locking plate combined with locking attachment plate in patients with periprosthetic femoral fracture around ipsilateral stem after total knee arthroplasty.

BACKGROUND: The purpose of this study was to introduce the surgical technique using long locking plate and locking attachment plate (LAP) in patient with periprosthetic femoral fracture around ipsilateral stem after total knee arthroplasty (TKA). Moreover, we sought to investigate the outcomes of this fixation technique and to propose a new subtype in the existing classification of periprosthetic femoral fractures. METHODS: From January 2013 to January 2022, thirty-four consecutive periprosthetic femoral fractures around ipsilateral stem following TKA with minimum 1-year follow-up were enrolled in this study. Most cases were fixed with long-locking plate and LAP using the MIPO technique. For subgroup analysis, we classified patients with stemmed hip implant (group H) and stemmed knee implant (group K). Bone union, American Knee Society Score (AKSS) scale, Knee Injury and Osteoarthritis Outcome Score for Joint Replacement, the Western Ontario and McMaster Universities Osteoarthritis Index for pain and function, and range of motion were investigated. RESULTS: The number of group H and K were 24 patients (70.6%) and 10 patients (29.4%), respectively. The mean age at operation was 71.5 years (range, 65‒85 years), and the mean follow-up period was 27.5 months (range, 12‒72 months). Bone union was confirmed radiographically in all patients, and the mean union time was 4.9 months (range, 3.5‒6 months). There were no significant differences in radiographic and clinical outcomes between the groups. CONCLUSIONS: Long-locking plate combined with LAP showed favorable radiographic and clinical outcomes in patients with periprosthetic femoral fracture around ipsilateral stem after TKA. LEVEL OF EVIDENCE: Level IV, Retrospective Case Series.

Particulated Costal Hyaline Cartilage Allograft With Subchondral Drilling Improves Joint Space Width and Second-Look Macroscopic Articular Cartilage Scores Compared With Subchondral Drilling Alone in Medial Open-Wedge High Tibial Osteotomy.

PURPOSE: To compare the articular cartilage regeneration based on second-look arthroscopy in patients who underwent medial open-wedge high tibial osteotomy (MOWHTO) combined with particulated costal hyaline cartilage allograft (PCHCA) implantation with those who underwent MOWHTO and subchondral drilling (SD). Moreover, we compared the clinical and radiographic outcomes between the groups. METHODS: From January 2014 to November 2020, patients with full-thickness cartilage defect on the medial femoral condyle who underwent MOWHTO combined with PCHCA (group A) or SD (group B) were reviewed. Fifty-one knees were matched after propensity score matching. The status of regenerated cartilage was classified according to the International Cartilage Repair Society-Cartilage Repair Assessment (ICRS-CRA) grading system and Koshino staging system, based on second-look arthroscopic findings. Clinically, the Knee Injury and Osteoarthritis Outcome Score, the Western Ontario and McMaster Universities Osteoarthritis Index, and range of motion were compared. Radiographically, we compared the differences in the minimum joint space width (JSW) and change in JSW. RESULTS: The average age was 55.5 years (range, 42-64 years), and the average follow-up period was 27.1 months (range, 24-48 months). Group A showed a significantly better cartilage status than group B based on the ICRS-CRA grading system and Koshino staging system (P < .001 and <.001, respectively). There were no significant differences in clinical and radiographic outcomes between groups. In group A, the minimum JSW at the last follow-up was significantly increased than that before surgery (P = .013), and a significantly greater increase in JSW was observed in group A (P = .025). CONCLUSIONS: When performed with MOWHTO, the combination of SD and PCHCA was associated with superior articular cartilage regeneration on the ICRS-CRA grading and Koshino staging on second-look arthroscopy performed at a minimum of 2 years follow-up than SD alone. However, there was no difference in clinical outcomes. LEVEL OF EVIDENCE: Level III, retrospective comparative study.

The Fontan Udenafil Exercise Longitudinal Trial: Subgroup Analysis.

The Pediatric Heart Network's Fontan Udenafil Exercise Longitudinal (FUEL) Trial (Mezzion Pharma Co. Ltd., NCT02741115) demonstrated improvements in some measures of exercise capacity and in the myocardial performance index following 6 months of treatment with udenafil (87.5 mg twice daily). In this post hoc analysis, we evaluate whether subgroups within the population experienced a differential effect on exercise performance in response to treatment. The effect of udenafil on exercise was evaluated within subgroups defined by baseline characteristics, including peak oxygen consumption (VO2), serum brain-type natriuretic peptide level, weight, race, gender, and ventricular morphology. Differences among subgroups were evaluated using ANCOVA modeling with fixed factors for treatment arm and subgroup and the interaction between treatment arm and subgroup. Within-subgroup analyses demonstrated trends toward quantitative improvements in peak VO2, work rate at the ventilatory anaerobic threshold (VAT), VO2 at VAT, and ventilatory efficiency (VE/VCO2) for those randomized to udenafil compared to placebo in nearly all subgroups. There was no identified differential response to udenafil based on baseline peak VO2, baseline BNP level, weight, race and ethnicity, gender, or ventricular morphology, although participants in the lowest tertile of baseline peak VO2 trended toward larger improvements. The absence of a differential response across subgroups in response to treatment with udenafil suggests that the treatment benefit may not be restricted to specific sub-populations. Further work is warranted to confirm the potential benefit of udenafil and to evaluate the long-term tolerability and safety of treatment and to determine the impact of udenafil on the development of other morbidities related to the Fontan circulation.Trial Registration NCT0274115.

Does Sarcopenia Accompanying End-Stage Knee Osteoarthritis Affect the Outcomes following Total Knee Arthroplasty?

Background and Objectives: This study aimed to investigate the prevalence of sarcopenia in patients undergoing total knee arthroplasty (TKA) for advanced knee osteoarthritis (OA), and to assess whether sarcopenia accompanying OA affects patient-reported outcome measures (PROMs) after TKA. We evaluated which predisposing factors could influence the development of sarcopenia in patients with advanced knee OA. Material and Methods: A total of 445 patients whose body composition, muscle strength, and physical performance could be measured before primary TKA were enrolled. Sarcopenia was defined according to the Asian Working Group for Sarcopenia 2019 criteria. Patients were categorized into sarcopenia (S, n = 42) and non-sarcopenia groups (NS, n = 403). PROMs were investigated using the Knee Injury and Osteoarthritis Outcome Score and Western Ontario and McMaster Universities Osteoarthritis Index. Additionally, postoperative complications and predisposing factors for sarcopenia were evaluated. Results: The incidence of sarcopenia in the entire sample was 9.4%; the prevalence was higher in men (15.4%) than in women (8.7%), and significantly increased with advancing age (p < 0.001). At the six-month follow-up, PROMs in group S were significantly inferior to those in group NS, except for the pain score; however, at the 12-month follow-up, no significant difference was observed between the groups. Multivariate logistic regression indicated that age, body mass index (BMI), and a higher modified Charlson Comorbidity Index (mCCI) were predisposing factors for sarcopenia. Conclusions: A higher prevalence of sarcopenia was observed in men with progressive knee OA. Up to six months after primary TKA, PROMs in group S were inferior to those in group NS, except for the pain score; however, no significant difference was observed between the groups at 12 months. Age, BMI, and higher mCCI were predisposing factors for sarcopenia in patients with OA.

The effects of ammonia acclimation on biogas recovery and the microbial population in continuous anaerobic digestion of swine manure.

This study investigated the ammonia toxicity and the acclimation of anaerobic microbiome in continuous anaerobic digestion of swine manure using unacclimated inoculum. When the total ammonia nitrogen concentration (TAN) reached 2.5 g N/L, the methane yield decreased from 254.1 ± 9.6 to 154.6 ± 9.9 mL/g COD. The free ammonia nitrogen concentration of the inhibited condition was 190 mg N/L. The methane yield was eventually recovered as 269.6 ± 3.6 mL/g COD with a further operation. Anaerobic toxicity assay (ATA) showed that mixed liquor from the recovered phase possessed enhanced tolerance to ammonia, not only within the exposed level in continuous operation (<2.5 g NH3/L) but also over the range (>2.5 g NH3/L). Microbial analysis revealed that continuous operation under ammonia stress resulted in the change of both bacterial and archaeal populations. The ammonia adaptation was concurrent with the archaeal population shift from Methanosaeta to Methanosarcina and Methanobacterium. The dominancy of Clostridia in bacterial population was found in the recovered phase. It is highly recommended to use an inoculum acclimated to a target ammonia level which can be pre-checked by ATA and to secure a start-up period for ammonia adaptation in the field application of anaerobic digestion for swine manure.

Development of convolutional neural network model for diagnosing meniscus tear using magnetic resonance image.

BACKGROUND: Deep learning (DL) is an advanced machine learning approach used in diverse areas, such as image analysis, bioinformatics, and natural language processing. A convolutional neural network (CNN) is a representative DL model that is advantageous for image recognition and classification. In this study, we aimed to develop a CNN to detect meniscal tears and classify tear types using coronal and sagittal magnetic resonance (MR) images of each patient. METHODS: We retrospectively collected 599 cases (medial meniscus tear = 384, lateral meniscus tear = 167, and medial and lateral meniscus tear = 48) of knee MR images from patients with meniscal tears and 449 cases of knee MR images from patients without meniscal tears. To develop the DL model for evaluating the presence of meniscal tears, all the collected knee MR images of 1048 cases were used. To develop the DL model for evaluating the type of meniscal tear, 538 cases with meniscal tears (horizontal tear = 268, complex tear = 147, radial tear = 48, and longitudinal tear = 75) and 449 cases without meniscal tears were used. Additionally, a CNN algorithm was used. To measure the model's performance, 70% of the included data were randomly assigned to the training set, and the remaining 30% were assigned to the test set. RESULTS: The area under the curves (AUCs) of our model were 0.889, 0.817, and 0.924 for medial meniscal tears, lateral meniscal tears, and medial and lateral meniscal tears, respectively. The AUCs of the horizontal, complex, radial, and longitudinal tears were 0.761, 0.850, 0.601, and 0.858, respectively. CONCLUSION: Our study showed that the CNN model has the potential to be used in diagnosing the presence of meniscal tears and differentiating the types of meniscal tears.

New Classification for Periprosthetic Distal Femoral Fractures Based on Locked-Plate Fixation Following Total Knee Arthroplasty: A Multicenter Study.

BACKGROUND: This study aimed to establish a new classification using locked-plate fixation for periprosthetic distal femoral fracture (PDFF) following total knee arthroplasty (TKA) and to determine when dual locked-plate fixation is necessary through defining this classification. METHODS: One-hundred fifteen consecutive PDFFs that underwent operative treatment were reviewed from 2011 to 2019 with minimum 1-year follow-up. Most PDFFs were fixed with single or dual locked-plate fixations using the minimally invasive plate osteosynthesis technique. Based on preoperative radiographs, PDFFs were classified according to the level of main fracture line relative to the anterior flange of femoral component: type I and II, main fracture line located proximal and distal to the anterior flange; and type III, component instability regardless of fracture line requiring revisional TKA. Furthermore, type II fractures were subclassified based on the direction of fracture beak as follows: type IIL, lateral-beak; type IIM, medial-beak. The incidence, treatment methods, and complications were analyzed according to the classification. RESULTS: Incidences of type I, IIL, IIM, and III were 64.4%, 8.7%, 24.3%, and 2.6%, respectively. Meanwhile, most PDFFs in type I and II were treated with lateral single locked-plate fixations, except for type IIM, which was treated with either single or dual locked-plate fixations. Overall complications were significantly higher in type II (28.9%) than in type I (10.8%, P = .019). In type IIM, bone union-related complications were significantly higher in single locked-plate fixation (50.0%) than in dual locked-plate fixation (5.6%; P = .013). CONCLUSION: The new classification provides practical and obvious strategies for the treatment of PDFF following TKA using locked-plate fixation. For type IIM fracture, dual plate fixation is necessary to prevent fixation failure or nonunion.

A Multivalent Vaccine Based on Ferritin Nanocage Elicits Potent Protective Immune Responses against SARS-CoV-2 Mutations.

The SARS-CoV-2 pandemic has created a global public crisis and heavily affected personal lives, healthcare systems, and global economies. Virus variants are continuously emerging, and, thus, the pandemic has been ongoing for over two years. Vaccines were rapidly developed based on the original SARS-CoV-2 (Wuhan-Hu-1) to build immunity against the coronavirus disease. However, they had a very low effect on the virus' variants due to their low cross-reactivity. In this study, a multivalent SARS-CoV-2 vaccine was developed using ferritin nanocages, which display the spike protein from the Wuhan-Hu-1, B.1.351, or B.1.429 SARS-CoV-2 on their surfaces. We show that the mixture of three SARS-CoV-2 spike-protein-displaying nanocages elicits CD4+ and CD8+ T cells and B-cell immunity successfully in vivo. Furthermore, they generate a more consistent antibody response against the B.1.351 and B.1.429 variants than a monovalent vaccine. This leads us to believe that the proposed ferritin-nanocage-based multivalent vaccine platform will provide strong protection against emerging SARS-CoV-2 variants of concern (VOCs).

Results of the FUEL Trial.

BACKGROUND: The Fontan operation creates a total cavopulmonary connection, a circulation in which the importance of pulmonary vascular resistance is magnified. Over time, this circulation leads to deterioration of cardiovascular efficiency associated with a decline in exercise performance. Rigorous clinical trials aimed at improving physiology and guiding pharmacotherapy are lacking. METHODS: The FUEL trial (Fontan Udenafil Exercise Longitudinal) was a phase III clinical trial conducted at 30 centers. Participants were randomly assigned udenafil, 87.5 mg twice daily, or placebo in a 1:1 ratio. The primary outcome was the between-group difference in change in oxygen consumption at peak exercise. Secondary outcomes included between-group differences in changes in submaximal exercise at the ventilatory anaerobic threshold, the myocardial performance index, the natural log of the reactive hyperemia index, and serum brain-type natriuretic peptide. RESULTS: Between 2017 and 2019, 30 clinical sites in North America and the Republic of Korea randomly assigned 400 participants with Fontan physiology. The mean age at randomization was 15.5±2 years; 60% of participants were male, and 81% were white. All 400 participants were included in the primary analysis with imputation of the 26-week end point for 21 participants with missing data (11 randomly assigned to udenafil and 10 to placebo). Among randomly assigned participants, peak oxygen consumption increased by 44±245 mL/min (2.8%) in the udenafil group and declined by 3.7±228 mL/min (-0.2%) in the placebo group (P=0.071). Analysis at ventilatory anaerobic threshold demonstrated improvements in the udenafil group versus the placebo group in oxygen consumption (+33±185 [3.2%] versus -9±193 [-0.9%] mL/min, P=0.012), ventilatory equivalents of carbon dioxide (-0.8 versus -0.06, P=0.014), and work rate (+3.8 versus +0.34 W, P=0.021). There was no difference in change of myocardial performance index, the natural log of the reactive hyperemia index, or serum brain-type natriuretic peptide level. CONCLUSIONS: In the FUEL trial, treatment with udenafil (87.5 mg twice daily) was not associated with an improvement in oxygen consumption at peak exercise but was associated with improvements in multiple measures of exercise performance at the ventilatory anaerobic threshold. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02741115.