Angiogenic Gene Therapy for Refractory Angina: Results of the EXACT Phase 2 Trial.

BACKGROUND: XC001 is a novel adenoviral-5 vector designed to express multiple isoforms of VEGF (vascular endothelial growth factor) and more safely and potently induce angiogenesis. The EXACT trial (Epicardial Delivery of XC001 Gene Therapy for Refractory Angina Coronary Treatment) assessed the safety and preliminary efficacy of XC001 in patients with no option refractory angina. METHODS: In this single-arm, multicenter, open-label trial, 32 patients with no option refractory angina received a single treatment of XC001 (1×1011 viral particles) via transepicardial delivery. RESULTS: There were no severe adverse events attributed to the study drug. Twenty expected severe adverse events in 13 patients were related to the surgical procedure. Total exercise duration increased from a mean±SD of 359.9±105.55 seconds at baseline to 448.2±168.45 (3 months), 449.2±175.9 (6 months), and 477.6±174.7 (12 months; +88.3 [95% CI, 37.1-139.5], +84.5 [95% CI, 34.1-134.9], and +115.5 [95% CI, 59.1-171.9]). Total myocardial perfusion deficit on positron emission tomography imaging decreased by 10.2% (95% CI, -3.1% to 23.5%), 14.3% (95% CI, 2.8%-25.7%), and 10.2% (95% CI, -0.8% to -21.2%). Angina frequency decreased from a mean±SD 12.2±12.5 episodes to 5.2±7.2 (3 months), 5.1±7.8 (6 months), and 2.7±4.8 (12 months), with an average decrease of 7.7 (95% CI, 4.1-11.3), 6.6 (95% CI, 3.5-9.7), and 8.8 (4.6-13.0) episodes at 3, 6, and 12 months. Angina class improved in 81% of participants at 6 months. CONCLUSIONS: XC001 administered via transepicardial delivery is safe and generally well tolerated. Exploratory improvements in total exercise duration, ischemic burden, and subjective measures support a biologic effect sustained to 12 months, warranting further investigation. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04125732.

Neural reward representations enable utilitarian welfare maximization.

From deciding which meal to prepare for our guests to trading-off the pro-environmental effects of climate protection measures against their economic costs, we often must consider the consequences of our actions for the well-being of others (welfare). Vexingly, the tastes and views of others can vary widely. To maximize welfare according to the utilitarian philosophical tradition, decision makers facing conflicting preferences of others should choose the option that maximizes the sum of subjective value (utility) of the entire group. This notion requires comparing intensities of preferences across individuals. However, it remains unclear whether such comparisons are possible at all, and (if they are possible) how they might be implemented in the brain. Here, we show that female and male participants can both learn the preferences of others by observing their choices, and represent these preferences on a common scale to make utilitarian welfare decisions. On the neural level, multivariate support vector regressions revealed that a distributed activity pattern in the ventromedial prefrontal cortex (VMPFC), a brain region previously associated with reward processing, represented preference strength of others. Strikingly, also the utilitarian welfare of others was represented in the VMPFC and relied on the same neural code as the estimated preferences of others. Together, our findings reveal that humans can behave as if they maximized utilitarian welfare using a specific utility representation and that the brain enables such choices by repurposing neural machinery processing the reward others receive.Significance statement In many situations politicians and civilians strive to maximize the welfare of social groups. If the preferences of group members are in conflict, identifying the utilitarian welfare-maximizing option requires that decision makers can compare the strengths of conflicting preferences on a common scale. Yet, there is a fundamental lack of understanding which brain mechanisms enable such comparisons of conflicting utilities. Here, we show that brain regions involved in reward processing compute welfare comparisons by representing the preferences of others with a common neural code. This provides a neurobiological mechanism to compute utilitarian welfare maximization as desired by moral philosophy in the Humean tradition.

Enhanced Photostability and Photoactivity of Ruthenium Polypyridyl-Based Photocatalysts by Covalently Anchoring Onto Reduced Graphene Oxide.

Recentstudies toward finding more efficient ruthenium metalloligands for photocatalysis applications have shown that the derivatives of the linear [Ru(dqp)2]2+ (dqp: 2,6-di(quinolin-8-yl)-pyridine) complexes hold significant promise due to their extended emission lifetime in the µs time scale while retaining comparable redox potential, extinction coefficients, and absorption profile in the visible region to [Ru(bpy)3]2+ (bpy: 2,2'-bipyridine) and [Ru(tpy)2]2+ (tpy: 2,2':6',2″-terpyridine) complexes. Nevertheless, its photostability in aqueous solution needs to be improved for its widespread use in photocatalysis. Carbon-based supports have arisen as potential solutions for improving photostability and photocatalytic activity, yet their effect greatly depends on the interaction of the metal complex with the support. Herein, we present a strategy for obtaining Ru-polypyridyl complexes covalently linked to aminated reduced graphene oxide (rGO) to generate novel materials with long-term photostability and increased photoactivity. Specifically, the hybrid Ru(dqp)@rGO system has shown excellent photostable behavior during 24 h of continual irradiation, with an enhancement of 10 and 15% of photocatalytic dye degradation in comparison with [Ru(dqp)2]2+ and Ru(tpy)@rGO, respectively, as well as remarkable recyclability. The presented strategy corroborates the potential of [Ru(dqp)2]2+ as an interesting photoactive molecule to produce more advantageous light-active materials by covalent attachment onto carbon-based supports.

Yeast sexes: mating types do not determine the sexes in Metschnikowia species.

Although filamentous Ascomycetes may produce structures that are interpreted as male and female gametangia, ascomycetous yeasts are generally not considered to possess male and female sexes. In haplontic yeasts of the genus Metschnikowia, the sexual cycle begins with the fusion of two morphologically identical cells of complementary mating types. Soon after conjugation, a protuberance emerges from one of the conjugants, eventually maturing into an ascus. The originating cell can be regarded as an ascus mother cell, hence as female. We tested the hypothesis that the sexes, female or male, are determined by the mating types. There were good reasons to hypothesize further that mating type α cells are male. In a conceptually simple experiment, we observed the early stages of the mating reaction of mating types differentially labeled with fluorescent concanavalin A conjugates. Three large-spored Metschnikowia species, M. amazonensis, M. continentalis, and M. matae, were examined. In all three, the sexes were found to be independent of mating type, cautioning that the two terms should not be used interchangeably.

Assessment of fatty infiltration of the hamstring muscles in chronic proximal hamstring ruptures and effect on clinical outcomes after surgical repair: a novel application of the Goutallier classification.

INTRODUCTION: Increased time to surgery has been previously associated with poorer clinical outcomes after surgical treatment of proximal hamstring ruptures, though the etiology remains unclear. The purpose of this study was to evaluate whether degree of muscle atrophy, as assessed using the Goutallier classification system, is associated with worse outcomes following surgical treatment of chronic proximal hamstring ruptures. MATERIALS AND METHODS: This was a retrospective case series of patients who underwent repair of proximal hamstring ruptures from 2012 to 2020 with minimum 2-year follow-up. Patients were included if they underwent primary repair of a proximal hamstring rupture ≥ 6 weeks after the date of injury and had accessible preoperative magnetic resonance imaging (MRI). Exclusion criteria were allograft reconstruction, endoscopic repair, or prior ipsilateral hip surgery. Patients were administered validated surveys: the modified Harris Hip Score (mHHS) and Perth Hamstring Assessment Tool (PHAT). Fatty atrophy on preoperative MRI was independently graded by two musculoskeletal radiologists using the Goutallier classification. Multivariate regression analysis was performed to evaluate associations of preoperative characteristics with muscle atrophy, as well as mHHS and PHAT scores. RESULTS: Complete data sets were obtained for 27 patients. A majority of this cohort was male (63.0%), with a mean age of 51.5 ± 11.8 years and BMI of 26.3 ± 3.8. The mean follow-up time was 62.6 ± 23.1 months, and the mean time from injury-to-surgery was 20.4 ± 15.3 weeks. The Goutallier grading inter-reader weighted kappa coefficient was 0.655. Regression analysis demonstrated that atrophy was not significantly associated with PHAT (p = 0.542) or mHHS (p = 0.574) at latest follow-up. Increased age was significantly predictive of muscle atrophy (ß = 0.62, p = 0.005) and was also found to be a significant predictor of poorer mHHS (ß = - 0.75; p = 0.037). CONCLUSIONS: The degree of atrophy was not found to be an independent predictor of clinical outcomes following repair of chronic proximal hamstring ruptures. Increasing age was significantly predictive of increased atrophy and poorer patient-reported outcomes.

Early outcomes of endovascular repairs of the aortic arch using thoracic branch endoprosthesis.

OBJECTIVE: The only commercially available thoracic branched endoprosthesis (TBE) for treatment of the aortic arch was released in 2022. Limited data outside of clinical trial results have been reported. This study describes the demographics, anatomic details, and outcomes for patients treated for zone 0 to 2 using TBEs outside of a clinical trial. METHODS: All patients treated using TBEs for zone 0 to 2 were included. Patients treated as part of the clinical trial for zone 0 to 1 (n = 6) were excluded. Patient demographics, comorbidities, anatomic and operative details, and outcomes were reported. Outcomes and survival were then compared between groups. RESULTS: Of 40 patients, six patients underwent repair of zone 0, three of zone 1, and 31 of zone 2. There were no differences in demographics, comorbidities, or operative details by zone of treatment; however, the frequency of genetic aortopathy differed (zone 0: 0%; zone 1: 67%; and zone 2: 6.4%; P < .01). Seventy-three percent of patients were treated for dissection vs 27% with isolated aneurysms. Of the patients, 2.5% were treated for rupture, 22% were treated for symptomatic aneurysms, and 75% were treated electively. Forty-eight percent of repairs included a proximal cuff, and 83% received distal extension. Technical success was achieved in 100% of patients. Mean fluoroscopy time was 18 minutes, and median fluoroscopy dose was 416 mGy. Sixty percent of patients had prior aortic ascending/arch repair. TBE was planned as part of a complete thoracoabdominal repair in 45% of patients. Thirty-day mortality was 2.5% overall, with a single death in a zone 0 patient that occurred at day 1 due to a myocardial infarction. There were no reinterventions within 30 days. All other outcomes were similar. The 30-day stroke rate was 5.0%. The strokes occurred at day 6 (zone 1) and day 15 (zone 2); however, both were due to occlusion of a prior proximal surgical bypass and unrelated to the TBE side branch or embolization. Specifically, both patients had occlusion of a branch of their prior zone 1 or zone 2 arch replacement. An endoleak occurred in 7.5% of patients at 30-day follow-up (type II: 5.0%; unknown: 2.5%). At a mean follow-up of 6.6 months, 100% of side branches were patent. CONCLUSIONS: Repair of the aortic arch including TBE can be performed electively and urgently with acceptable stroke and death rates. TBE provides a valuable tool for patients requiring complete repair of a thoracoabdominal aneurysm. Continued investigation is underway to assess long-term safety and efficacy outside of the clinical trial.

Imaging assessment of spine infection.

This article comprehensively reviews current imaging concepts in spinal infection with primary focus on infectious spondylodiscitis (IS) as well as the less common entity of facet joint septic arthritis (FSA). This review encompasses the multimodality imaging appearances (radiographs, CT, MRI, and nuclear imaging) of spinal infection-both at initial presentation and during treatment-to aid the radiologist in guiding diagnosis and successful management. We discuss the pathophysiology of spinal infection in various patient populations (including the non-instrumented and postoperative spine) as well as the role of imaging-guided biopsy. We also highlight several non-infectious entities that can mimic IS (both clinically and radiologically) that should be considered during image interpretation to avoid misdiagnosis. These potential mimics include the following: Modic type 1 degenerative changes, acute Schmorl's node, neuropathic spondyloarthropathy, radiation osteitis, and inflammatory spondyloarthropathy (SAPHO syndrome).

Utility of a 2D kinematic HASTE sequence in magnetic resonance imaging assessment of adjacent segment degeneration following anterior cervical discectomy and fusion.

OBJECTIVES: To evaluate a dynamic half-Fourier acquired single turbo spin echo (HASTE) sequence following anterior cervical discectomy and fusion (ACDF) at the junctional level for adjacent segment degeneration comparing dynamic listhesis to radiographs and assessing dynamic cord contact and deformity during flexion-extension METHODS: Patients with ACDF referred for cervical spine MRI underwent a kinematic flexion-extension sagittal 2D HASTE sequence in addition to routine sequences. Images were independently reviewed by three radiologists for static/dynamic listhesis, and compared to flexion-extension radiographs. Blinded assessment of the HASTE sequence was performed for cord contact/deformity between neutral, flexion, and extension, to evaluate concordance between readers and inter-modality agreement. Inter-reader agreement for dynamic listhesis and impingement grade and inter-modality agreement for dynamic listhesis on MRI and radiographs was assessed using the kappa coefficient and percentage concordance. RESULTS: A total of 28 patients, mean age 60.2 years, were included. Mean HASTE acquisition time was 42 s. 14.3% demonstrated high grade dynamic stenosis (> grade 4) at the adjacent segment. There was substantial agreement for dynamic cord impingement with 70.2% concordance (kappa = 0.62). Concordance across readers for dynamic listhesis using HASTE was 81.0% (68/84) (kappa = 0.16) compared with 71.4% (60/84) (kappa = 0.40) for radiographs. Inter-modality agreement between flexion-extension radiographs and MRI assessment for dynamic listhesis across the readers was moderate (kappa = 0.41; 95% confidence interval: 0.16 to 0.67). CONCLUSIONS: A sagittal flexion-extension HASTE cine sequence provides substantial agreement between readers for dynamic cord deformity and moderate agreement between radiographs and MRI for dynamic listhesis. CLINICAL RELEVANCE STATEMENT: Degeneration of the adjacent segment with instability and myelopathy is one of the most common causes of pain and neurological deterioration requiring re-operation following cervical fusion surgery. KEY POINTS: • A real-time kinematic 2D sagittal HASTE flexion-extension sequence can be used to assess for dynamic listhesis, cervical cord, contact and deformity. • The additional kinematic cine sequence was well tolerated and the mean acquisition time for the 2D HASTE sequence was 42 s (range 31-44 s). • A sagittal flexion-extension HASTE cine sequence provides substantial agreement between readers for dynamic cord deformity and moderate agreement between radiographs and MRI for dynamic listhesis.

Decreased Hip Labral Width Measured on Preoperative Magnetic Resonance Imaging Is Associated With Greater Revision Rate After Primary Arthroscopic Labral Repair for Femoroacetabular Impingement Syndrome at 5-Year Follow-Up.

PURPOSE: To examine the associations between hip labral width and patient-reported outcomes, clinical threshold achievement rates, and rate of reoperation among patients with femoroacetabular impingement syndrome (FAIS) who underwent hip arthroscopy and labral repair at minimum 5-year follow-up. METHODS: Patients were identified from a prospective database who underwent primary hip arthroscopy for treatment of labral tears and FAIS. Modified Harris Hip Score (mHHS) and Nonarthritic Hip Score (NAHS) were recorded preoperatively and at 5-year follow-up. Achievement of the minimal clinically important difference (MCID), substantial clinical benefit (SCB), and patient-acceptable symptom state (PASS) was determined using previously established values. Labral width magnetic resonance imaging measurements were performed by 2 independent readers at standardized "clockface" locations. Patients were stratified into 3 groups at each position: lower-width (<½ SD below mean), middle-width (within ½ SD of mean), and upper-width (>½ SD above mean). Multivariable regression was used to evaluate associations of labral width with patient-reported outcomes and reoperation rate. RESULTS: Seventy-three patients (age: 41.0 ± 12.0 years; 68.5% female) were included. Inter-rater reliability for labral width measurements was high at all positions (intraclass correlation coefficient 0.94-0.96). There were no significant intergroup differences in mHHS/NAHS improvement (P > .05) or in achievement rates of MCID/SCB/PASS at each clockface position (P > .05). Eleven patients (15.1%) underwent arthroscopic revision and 4 patients (5.5%) converted to total hip arthroplasty. Multivariable analysis found lower-width groups at 11:30 (odds ratio 1.75, P = .02) and 3:00 (odds ratio 1.59, P = .04) positions to have increased odds of revision within 5 years; however, labral width was not associated with 5-year improvement in mHHS/NAHS, achievement of MCID/PASS/SCB, or conversion to total hip arthroplasty (P > .05). CONCLUSIONS: Hip labral width <½ SD below the mean measured on preoperative magnetic resonance imaging at 11:30- and 3:00-clockface positions was associated with increased odds of reoperation after arthroscopic labral repair and treatment of FAIS. Labral width was not associated with 5-year improvement of mHHS, NAHS, achievement of clinical thresholds, or conversion to arthroplasty. LEVEL OF EVIDENCE: Level IV, case series.

Dissemination and implementation analysis of the Ross procedure in adults: time to update the guidelines?

Background: The science of dissemination and implementation (D&I) aims to improve the quality and effectiveness of care by addressing the challenges of incorporating research and evidence-based practice into routine clinical practice. This lens of D&I has challenged the interpretation and incorporation of data, noting that failure of a given therapy may not reflect lack of efficacy, but instead reflect an imperfect implementation. The aim of this manuscript is to review the influence of the Ross procedure's historical context on its D&I. Methods: A contextual baseline of the Ross procedure was defined from the procedure's original description in the literature to major publications since the 2017 valvular heart disease guidelines. D&I evaluation was conducted using the Consolidated Framework for Implementation Research (CFIR), using constructs from each of the five respective domains to define the main determinants. Results: Each of the five CFIR domains appears to be correlated with a factor influencing the Ross procedure's varied history of enthusiasm and acceptance. The complex nature of Ross required adaptation for optimization, with a strong correlation of center volume on outcomes that were not considered in non-contemporary studies. Outcomes later published from those studies influenced social and cultural contexts within the aortic surgery community, and led to further organizational uncertainty, resulting in slow guideline incorporation. Conclusions: The D&I of the Ross procedure was a result of inadequate appreciation of technical complexity, effect of patient selection, and complex aortic surgery experience, resulting in dismissal of an efficacious procedure due to a misunderstanding of effectiveness.

Tips and tricks in ultrasound-guided musculoskeletal interventional procedures.

Ultrasound visualization affords proceduralists versatile and accurate guidance for a variety of percutaneous, minimally invasive procedures in the musculoskeletal system including joint (intra-articular) injections or aspirations, intra-bursal injections, peritendinous, and perineural injections. A variety of percutaneous procedures are traditionally performed blindly, but may be more easily or more accurately performed with the real-time assistance of ultrasound guidance. Other procedures are only possible utilizing image-guidance, due to the required precision of the injection because of delicate local anatomy or depth of the injection; ultrasound is a safe, portable, and widespread modality that can be used to assist the proceduralist in localizing the needle tip in such cases, to ensure safe and accurate delivery of the medication, most frequently a solution of steroid and anesthetic. This review aims to provide a foundational approach to ultrasound-guided procedures in the musculoskeletal system, offering tips and tricks that can be employed in many different procedures including intra-articular, juxta-articular, and perineural injections for a multitude of clinical scenarios. Technical considerations regarding ultrasound transducer selection, sonographic technique, as well as common indications, contraindications, and complications of these procedures, are presented. Additionally, a variety of pharmacologic considerations for proceduralists contemplating ultrasound-guided injections are discussed.

Natural history of the distal aorta following elective root replacement in patients with Marfan syndrome.

OBJECTIVE: It is unclear if the addition of a prophylactic arch operation is beneficial at the time of root replacement in patients with Marfan syndrome (MFS). This project aims to understand the fate of the distal aorta following elective root replacement in patients with MFS. METHODS: Between 2000 and 2019, 124 adult patients with MFS were identified as having undergone elective aortic root replacement with a clamped distal aortic anastomosis during their lifetime. Serial axial imaging was analyzed. The primary outcome was a composite of subsequent type B aortic dissection (TBAD), aneurysmal degeneration (>4 cm), and aortic reintervention. Secondary outcomes included subsequent TBAD and mortality. RESULTS: Mean age at root replacement was 33.3 years. Median follow-up was 11.3 years. Thirty-one patients (25%) experienced the primary outcome, with no survival difference (P = .9). The crossclamp and aortic cannulation sites were stable (growth rate, 0.33 mm/year), and 2 patients (1.6%) required reintervention there. Twenty-three patients (19.8%) experienced subsequent TBAD. Patients with TBAD had a higher rate of distal degeneration (P < .001), but no significant change in survival (P = .2). Preoperative hypertension (odds ratio, 3.96; P < .05) and younger age at root replacement (odds ratio, 1.05; P < .05) increased the risk of TBAD, based on regression analysis. CONCLUSIONS: The distal aorta (including the clamp and cannulation site) overall appears stable in patients with MFS following elective root replacement without prophylactic arch operation. Development of TBAD seems to be the primary driver of distal degeneration. Factors associated with TBAD development included hypertension, underscoring the importance of strict blood pressure control in these patients.

A multidisciplinary multistage complete mega aorta replacement and utilization of extracorporeal membrane oxygenation in thoracoabdominal aneurysm repair.

A 49-year-old woman underwent a 11-month multistage complete replacement of a mega aorta. Replacement stages included ascending aorta and arch replacement in conjunction with a frozen elephant trunk thoracic endovascular aortic repair, extension of thoracic endovascular aortic repair to zone 5, and open repair of the thoracoabdominal aneurysm with the use of venoarterial extracorporeal membrane oxygenation for circulatory support. This case illustrates the complexity of repairing a mega aorta, the multidisciplinary care and staging needed for repair, and the use of peripheral venoarterial extracorporeal membrane oxygenation for circulatory perfusion during thoracoabdominal aneurysm repair.

Phototoxicity of Tridentate Ru(II) Polypyridyl Complex with Expanded Bite Angles toward Mammalian Cells and Multicellular Tumor Spheroids.

Tridentate ligand-coordinated ruthenium (II) polypyridyl complexes with large N-Ru-N bite angles have been shown to promote ligand field splitting and reduce singlet-triplet state mixing leading to dramatically extended emission quantum yields and lifetimes under ambient conditions. These effects are anticipated to enhance their photoinduced singlet oxygen production, promoting prospects for such complexes as type II phototherapeutics. In this contribution, we examined this putative effect for [Ru(bqp)(bqpCOOEt)]2+, Ru-bqp-ester, a heteroleptic complex containing bqp = [2,6-bi(quinolin-8-yl)pyridine], a well-established large bite angle tridentate ligand, as well as its peptide conjugates [Ru(bqp)(bqpCONH-ahx-FrFKFrFK(Ac)-CONH2)]5+ (Ru-bqp-MPP) and [Ru(bqp) (bqp)(CONH-ahx-RRRRRRRR-CONH2)]10+ (Ru-bqp-R8) that were prepared in an effort to promote live cell/tissue permeability and targeting of the parent. Membrane permeability of both parent and peptide conjugates were compared across 2D cell monolayers; A549, Chinese hamster ovary, human pancreatic cancer (HPAC), and 3D HPAC multicellular tumor spheroids (MCTS) using confocal microscopy. Both the parent complex and peptide conjugates showed exceptional permeability with rapid uptake in both 2D and 3D cell models but with little distinction in permeability or distribution in cells between the parent or peptide conjugates. Unexpectedly, the uptake was temperature independent and so attributed to passive permeation. Both dark and photo-toxicity of the Ru(II) complexes were assessed across cell types, and the parent showed notably low dark toxicity. In contrast, the parent and conjugates were found to be highly phototoxic, with impressive phototoxic indices (PIs) toward HPAC cell monolayers in particular, with PI values ranging from ∼580 to 760. Overall, our data indicate that the Ru(II) parent complex and its peptide conjugates show promise at both cell monolayers and 3D MCTS as photosensitizers for photodynamic therapy.

Operative repair of right intrathoracic subclavian artery aneurysms in patients with genetic arteriopathy.

True intrathoracic subclavian artery aneurysms (SCAAs) are rare and have various etiologies. Right intrathoracic SCAAs pose specific anatomic challenges to repair. We present three different operative approaches, open, endovascular, and hybrid repair, for the repair of a right intrathoracic SCAA in three patients with genetic arteriopathy: Marfan syndrome, vascular Ehlers-Danlos syndrome, and unspecified Ehlers-Danlos syndrome, respectively. These cases demonstrate an individualized operative approach based on the genetic diagnosis for each patient presenting with a right intrathoracic SCAA.

Extended and weightbearing wrist 3-T MRI using a novel harness and flexible 24-channel glove coil to evaluate carpal kinematics: a pilot study in 10 volunteers.

BACKGROUND: Wrist pain in the extended or extended weightbearing positions may be incompletely evaluated using standard magnetic resonance imaging (MRI) with standard rigid clamshell coils in the neutral position. PURPOSE: To evaluate a flexible 24-channel glove coil and harness when imaging the wrist in neutral, dorsally extended, and weightbearing positions. MATERIAL AND METHODS: Ten wrists in 10 asymptomatic volunteers (mean age = 29 years) were scanned. Participants underwent 3-T MRI using the harness and flexible glove coil, acquiring sagittal turbo spin echo (TSE) and half-Fourier acquisition single-shot turbo spin echo (HASTE) pulse sequences. Static TSE images were obtained in neutral, extended, and weightbearing positions using proton density parameters and independently evaluated by two radiologists for: dorsal radiocarpal ligament thickness; radiocapitate, radiolunate, and capitatolunate angles; palmar translation of the lunate on the radius; angulation of the extensor tendons; and distance from the distal extensor retinaculum to Lister's tubercle. Cine HASTE images were dynamically acquired between neutral-maximum extension to measure the radiocapitate angle. RESULTS: Good reader agreement was observed (r > 0.73) for all measurements except palmar translation in the neutral position (r = 0.27). Significant increases in dorsal radiocarpal ligament thickness; radiocapitate, radiolunate and capitolunate angulation; and extensor tendon angulation were observed between the neutral and extended positions (P < 0.001). A further significant increase in these metrics between extended and weightbearing positions was also seen (P < 0.01). CONCLUSION: Significant increases in dorsal radiocarpal ligament thickness, articular and tendon angulations occur during wrist extension, that further increase with dorsal weightbearing.

Musculoskeletal Soft-tissue Masses: MR imaging-Ultrasonography Correlation, with an Emphasis on the 2020 World Health Organization Classification.

Evaluation of soft-tissue masses has become a common clinical practice indication for imaging with both ultrasound and MR imaging. We illustrate the ultrasonography and MR imaging appearances of soft-tissue masses based on the various categories, updates, and reclassifications of the 2020 World Health Organization classification.

Does valve size impact hemodynamic, left ventricular mass regression, and prosthetic valve deterioration with a sutureless aortic valve?

OBJECTIVE: To assess the mid-term clinical outcomes, hemodynamics, left ventricular (LV) mass regression, and structural valve deterioration (SVD) in patients implanted with the Perceval aortic sutureless valve across valve sizes. METHODS: Data were obtained from a multicenter European trial and a US Investigational Device Exemption trial. Echocardiography data were analyzed by an echocardiography core lab. A mixed-effects regression model was used to assess relationships between hemodynamic outcomes, time from the procedure, and valve sizes. The Valve Academic Research Consortium (VARC)-3 definition for bioprosthetic valve failure was applied. RESULTS: A Perceval sutureless valve was implanted in 970 patients. The median patient age was 77.8 years, 57.2% were female, the median Society of Thoracic Surgeons predicated risk of mortality was 3.3% (range, 2.1%-6.2%), and 33.4% had a concomitant procedure. The median clinical follow-up was 45.7 months (range, 28.2-76.1 months). Small and medium valves were implanted more commonly in women than in men (16.9% vs 1.9% for small and 55.1% vs 19.5% for medium; P < .001). The mean aortic valve gradients decreased significantly postimplantation and remained stable across all valve sizes throughout the follow-up period. All patients were free from severe patient-prosthesis mismatch (with an effective orifice area/m2 of >0.8). Significant LV mass regression was documented regardless valve sizes, plateaued at -9.1% at 5 years. Freedom from SVD and reintervention were 95.2% and 96.3%, respectively, at 5 years and were independent of implanted valve size (P = .22). The VARC-3 stage 3 bioprosthetic valve failure rate was low, 2.8% at 5 years. CONCLUSIONS: The Perceval valve demonstrated low and stable mean gradients, significant LV mass regression, and low SVD and reintervention rates across all valve sizes.

Screening and activity of potential gastrointestinal probiotic lactic acid bacteria against Yersinia ruckeri O1b.

Yersiniosis of cultured Atlantic salmon is a recurrent fish health management challenge in many continents. The causative organism, Yersinia ruckeri, can reside latently in the gut and lead to acute infection and disease during hatchery and sea-transfer stages. One potential prevention approach is the administration of probiotic bacteria to suppress gut colonization of Y. ruckeri. Our study aimed to isolate and identify anti-Yersinia activity among lactic acid bacteria (LAB) isolated from the gastrointestinal tract (GIT) of aquatic animals. Of the 186 aquatic GIT isolates examined, three strains showed diffusible antimicrobial activity towards Y. ruckeri O1b. Analysis of 16 s rRNA gene sequences indicated the three bacterial strains were Enterococci, related to Enterococcus sp. (99%), Enterococcus thailandicus (99%), and Enterococcus durans (99%). Anti-Yersinia activity was maintained at neutral pH (~6.5-7.0), and in-vitro environmental tolerance assays showed the three strains could withstand simulated salmonids gastrointestinal tract conditions of: low pH (3.4) and 3% bile salt content. All three Enterococci strains showed higher adhesion to the intestinal mucus of Atlantic salmon than Y. ruckeri O1b (E. durans 24%, E. enterococcus sp. 25% and E. thailandicus 98%, compared to Y. ruckeri O1b 5%). However, only Enterococcus sp. and E. thailandicus were able to grow in the salmon intestinal mucus broth while E. durans showed no growth. Anti-Yersinia activity was completely inactivated by proteinase-K treatment, suggesting that the active compound/s are proteinaceous and may be bacteriocin-like inhibitory substances (BLIS). Our data indicate that Enterococcus sp. MA176 and E. thailandicus MA122 are potential probionts for the prevention of yersiniosis in salmonids. Further in-vivo studies are required to determine whether these bacteria reduce the incidence of yersiniosis in Atlantic salmon.