Citations

Arterial stiffness predicts cardiovascular disease, the leading cause of death worldwide. Ultrasound elastography methods that measure wave velocity have promise for evaluating the stiffness of blood vessels in vivo. However, vessel geometry modulates wave velocity by inducing geometric dispersion. Here, we compare Young's modulus E estimates obtained using in vivo wave velocity measurements and techniques that either do or do not consider geometry to ex vivo reference E values from mechanical testing . An acoustic radiation force was applied to generate propagating waves in the right common carotid artery (N = 9) and external jugular vein (N = 10) of anesthetized pigs. Vessels were imaged with ultrafast ultrasound to measure wave motion. Group velocity cg was estimated from wave motion using a Radon transform. E was estimated from cg using a bulk media assumption which neglects geometry, as well as the Moens–Korteweg equation and a semi-analytical finite element model, which consider geometry. Pigs were euthanized and vessels were excised. Ring-shaped samples were extracted and tested in a uniaxial tension setup to obtain reference E values for comparison with E values obtained from wave-based techniques. Techniques considering geometry exhibited higher correlation with reference E values, underscoring the need to incorporate geometry for accurate vascular elastography assessments.

Context Musculoskeletal (MSK) diagnostic ultrasound (US) is increasingly being utilized by physicians to evaluate athletes in outpatient clinics, on the sidelines, and in athletic training facilities. Having a thorough understanding of MSK US will help athletic trainers (ATs) better assist physicians who perform MSK US. Objective To determine if a longitudinal 6-month MSK anatomy and US course would increase ATs’ ability to acquire, label, and optimize US images of normal structures and improve their overall confidence in assisting with performing US and to determine if demographic factors, work-related factors, or higher self-reported confidence was associated with better performance. Design Prospective cohort study. Setting Academic institution. Other Participants Seventeen ATs working with sports medicine physicians at 3 institutions. Interventions Longitudinal 6-month MSK anatomy and US course. Main Outcome Measures Ultrasound image scores (normal structures scored on a 5-point scale) were assessed precourse, during the course, and postcourse. Scores were compared across time points for the assessed body regions (knee, ankle/foot, shoulder, elbow/wrist/hand, and hip). Associations with demographic factors, US experience, and AT self-reported confidence were explored. Results Seventeen ATs completed the course. There was a significant difference among the average overall precourse (average: 1.34/5, range: 0/5 to 4.23/5), during-course (average = 3.53/5; range, 2.6/5 to 4.37/5), and postcourse (average = 3.83/5; range, 2.33/5 to 4.67/5) image scores [χ2(2) = 24.47, P < .001]. There was a significant positive correlation between the numbers of days (rs[17] = 0.62, P = .01) and hours (rs[17] = 0.55, P = .02) per week that the AT spent observing or performing US scanning and the postcourse overall image scores. The ATs’ confidence in identifying structures when they scan and postcourse overall image scores were marginally correlated but not significant (rs[17] = 0.47, P = .06). Conclusions A comprehensive longitudinal MSK diagnostic US course may have resulted in significant improvements in an AT’s ability to acquire, label, and optimize US images of normal MSK structures that are commonly injured by active persons.

Abstract Oligodendroglioma is characterized by oligodendrocyte-like histology, mutation in the IDH genes, along with codeletion of chromosome arms 1p and 19q. Treatment for oligodendrogliomas combines surgery, followed by observation, and chemotherapy and/or radiotherapy when tumors progress. Most oligodendrogliomas eventually recur with a more aggressive phenotype, leading to patient mortality but molecular mechanisms remain poorly understood. To investigate the molecular trajectory of oligodendroglioma, we collected more than 270 longitudinal samples from over 130 oligodendroglioma patients, to perform whole genome or whole exome sequencing, bulk RNA, and single-nucleus RNA sequencing (n = 30 samples). Common mutations in IDH1/2, TERT promoter, CIC, and FUBP1 were observed. About half of the CIC and FUBP1 mutations occurred in the initial sample and persisted stably throughout recurrence. The majority of PIK3CA and PIK3R1 mutations were either shared or present in recurrences only implicating the PI3K pathway in oligodendroglioma recurrence. Mutational signature analysis revealed 34.5% of tumors treated with alkylating agents acquired SBS11/SBS31 associated hypermutation. By integrating signatures with clonality estimates, we approximated the timing of mutational processes and found that clonal timings of treatment related mutations correlate with the treatment administration date. We found that aging signature-related mutations were mostly clonal, and treatment signature-related mutations were more likely to be sub-clonal, supporting the late emergence of these mutations following treatment. We observed increased somatic copy number alterations in oligodendroglioma recurrences, reflected in notable chromosome 4 losses. Associating treatment with snRNAseq derived cellular states, we observed a significant increase in the fraction of proliferating stem-like cells in the hypermutator versus non-hypermutator recurrent samples. These findings shed light on the molecular changes occurring in oligodendrogliomas following treatment and provide insights that may aid in targeting treatment resistance.

AbstractAnti‐CD19 chimeric antigen receptor T‐cell therapy (CART) has revolutionized the outcomes of relapsed and/or refractory B‐cell non‐Hodgkin lymphoma. However, CART is still limited by its availability, toxicity, and response durability. Not all patients make it to the CART infusion phase due to disease progression. Among those who receive CART, a significant number of patients experience life‐threatening cytokine release syndrome toxicity, and less than half maintain a durable response with the majority relapsing in pre‐existing sites of disease present pre‐CART. Radiation therapy stands as a promising peri‐CART and salvage treatment that can improve the outcomes of these patients. Evidence suggests that bridging radiotherapy prior to CART controls the disease during the manufacturing period, augments response rates and local control, cytoreduces/debulks the disease and decreases the severity of cytokine release syndrome, and may prolong disease‐free intervals and survival especially in patients with bulky disease. Consolidative radiotherapy for residual post‐CART disease alters the pattern of relapse and improves local recurrence‐free and progression‐free survivals. Salvage radiotherapy for relapsed post‐CART disease has favorable survival outcomes when delivered comprehensively for patients with limited relapsed disease and palliates symptoms for patients with diffuse relapsed disease. The biology of the disease during the peri‐CART period is poorly understood, and further studies investigating the optimal timing and dosing of radiation therapy (RT) are needed. In this review, we tackle the most significant challenges of CART, review and propose how RT can help mitigate these challenges, and provide The Mayo Clinic experts' approach on incorporating RT with CART.

BACKGROUND: There are limited data about changes in cardiac function (cardiac reverse remodeling) and heart failure indices after transcatheter tricuspid valve-in-valve replacement (TT-VIVR). The purpose of this study was to evaluate cardiac reverse remodeling and temporal changes in heart failure indices after TT-VIVR in adults with congenital heart disease. METHODS: Retrospective cohort study of adults with congenital heart disease that underwent TT-VIVR and had >6 months of follow-up (January 1, 2011, to April 30, 2023). Echocardiographic indices of cardiac remodeling and heart failure indices (New York Heart Association class, NT-proBNP (N-terminal pro-brain natriuretic peptide), glomerular filtration rate, and model for end-stage liver disease excluding international normalized ratio score) were assessed preintervention and at 1-, 3-, and 5-year postintervention. RESULTS: Of 39 patients (age 39 [32–46] years), 14 (36%) and 25 (64%) received Melody valve and Sapien valve prosthesis, respectively. At 1-year post-TT-VIVR, there was a temporal improvement in right atrial reservoir strain (17±8% versus 22±8%, P <0.001), right atrial volume (81 [59–108] versus 63 [48–82] mL/m 2 , P <0.001), right atrial pressure (12±4% versus 6±4%, P <0.001), and right ventricular global longitudinal strain (−15±7% versus −20±7%, P <0.001). Similarly, there was a temporal improvement in NT-proBNP, glomerular filtration rate, model for end-stage liver disease excluding international normalized ratio score, and New York Heart Association class. The temporal improvements in heart failure indices and valve function were maintained at 3- and 5-year post-TT-VIVR. CONCLUSIONS: Considering the significant mortality risk associated with reoperations for tricuspid valve replacement, these data suggest favorable outcomes after TT-VIVR, and support TT-VIVR as a viable alternative to surgical tricuspid valve replacement, especially in high-risk patients.

Introduction: Fontan pathway obstruction is a serious complication characterized by an anatomical or functional narrowing anywhere in the cavo-pulmonary pathways. Here we report the first case where an innovative Fontan conduit rehabilitation procedure with intravascular lithotripsy was used achieving a significant increase in the pathway size. Case: A 28-year-old male with tricuspid atresia status-post Fontan palliation (age 23 months) with bare metal stent implant to treat obstruction at age 15, presented with syncope, ascites and varicose veins. Imaging studies revealed a cirrhotic liver morphology and Fontan pathway obstruction with minimal diameter of 12 mm. Cardiac catheterization confirmed severe Fontan conduit obstruction in addition to LPA stenosis. Serial covered Cheatham-Platinum stents were implanted for conduit coverage followed by Palmaz stents. Non-compliant Atlas balloon dilation to 20 atm was performed without expansion of the Fontan pathway beyond 12 mm due to severe calcification. A 7.0 x 60 mm shock-wave lithotripsy balloon was added alongside the Atlas balloon to modulate the heavily calcified wall with subsequent expansion of the conduit to 21 mm after inflating the Atlas balloon to 14 atm. Discussion: Several studies demonstrated that transcatheter stenting of stenotic Fontan conduits can be safely performed. Intravascular lithotripsy has emerged as a novel therapy for the treatment of coronary vascular calcification. We report the first case of an innovative percutaneous Fontan conduit rehabilitation procedure using a lithotripsy shock wave balloon in an adult with severely calcified Fontan pathway obstruction and prior stents, achieving a 75% increase in the pathway size without significant complications. Further studies are needed to evaluate the long-term safety and efficacy of this novel approach, but this case presents an exciting option for future directions in the percutaneous treatment of Fontan pathway obstruction.

AbstractBackgroundThe Harmony TPV25 transcatheter pulmonary valve (Medtronic Inc.) is constructed with a self‐expanding stent frame comprising six zigged nitinol wires sewn together and covered with knitted polyester fabric, with flared inflow and outflow ends and a porcine pericardial valve sutured to the central portion of the device. It was approved for treatment of pulmonary regurgitation after prior right ventricular outflow tract repair in 2021. Early outcomes of this procedure have been excellent, but little is known about valve durability or ultimate mechanisms of dysfunction.MethodsWe collected data on patients who underwent reintervention for TPV25 dysfunction and described findings related to distortion of the stent frame and tissue accumulation.ResultsWe describe six patients who underwent valve‐in‐valve implant for TPV25 obstruction (peak catheterization gradient peak 28–73 mmHg) 10–28 months after implant. In all cases, there was tissue accumulation within the inflow and valve‐housing segments of the device and deformation of the self‐expanding valve frame characterized by variable circumferential narrowing at the junction between the valve housing and the inflow and outflow portions of the device, with additional geometric changes in all segments. All six patients underwent valve‐in‐valve implant that results in a final peak gradient ≤10 mmHg and no regurgitation.DiscussionThe occurrence of short‐term Harmony TPV25 dysfunction in multiple patients with a similar appearance of frame distortion and tissue accumulation within the inflow and valve housing portions of the device suggests that this may be an important failure mechanism for this valve. Potential causes of the observed findings are discussed. It is possible to treat this mechanism of TPV25 dysfunction with valve‐in‐valve implant using balloon expandable transcatheter valves.

SummaryMantle cell lymphoma (MCL) is clinically and biologically heterogeneous. While various prognostic features have been proposed, none currently impact therapy selection, particularly in older patients, for whom treatment is primarily dictated by age and comorbidities. Herein, we undertook a comprehensive comparison of clinicopathological features in a cohort of patients 60 years and older, uniformly treated with bendamustine and rituximab, with a median survival of >8 years. The strongest prognostic indicators in this cohort were a high‐risk call by a simplified MCL international prognostic index (s‐MIPI) (HR: 3.32, 95% CI: 1.65–6.68 compared to low risk), a high‐risk call by MCL35 (HR: 10.34, 95% CI: 2.37–45.20 compared to low risk) and blastoid cytology (HR: 4.21, 95% CR: 1.92–9.22 compared to classic). Patients called high risk by both the s‐MIPI and MCL35 had the most dismal prognosis (HR: 11.58, 95% CI: 4.10–32.72), while those with high risk by either had a moderate but clinically relevant prognosis (HR: 2.95, 95% CI: 1.49–5.82). A robust assay to assess proliferation, such as MCL35, along with stringent guidelines for cytological evaluation of MCL, in combination with MIPI, may be a strong path to risk‐stratify older MCL patients in future clinical trials.

ImportanceIncreased white matter hyperintensity (WMH) volume is a common magnetic resonance imaging (MRI) finding in both autosomal dominant Alzheimer disease (ADAD) and late-onset Alzheimer disease (LOAD), but it remains unclear whether increased WMH along the AD continuum is reflective of AD-intrinsic processes or secondary to elevated systemic vascular risk factors.ObjectiveTo estimate the associations of neurodegeneration and parenchymal and vessel amyloidosis with WMH accumulation and investigate whether systemic vascular risk is associated with WMH beyond these AD-intrinsic processes.Design, Setting, and ParticipantsThis cohort study used data from 3 longitudinal cohort studies conducted in tertiary and community-based medical centers—the Dominantly Inherited Alzheimer Network (DIAN; February 2010 to March 2020), the Alzheimer’s Disease Neuroimaging Initiative (ADNI; July 2007 to September 2021), and the Harvard Aging Brain Study (HABS; September 2010 to December 2019).Main Outcome and MeasuresThe main outcomes were the independent associations of neurodegeneration (decreases in gray matter volume), parenchymal amyloidosis (assessed by amyloid positron emission tomography), and vessel amyloidosis (evidenced by cerebral microbleeds [CMBs]) with cross-sectional and longitudinal WMH.ResultsData from 3960 MRI sessions among 1141 participants were included: 252 pathogenic variant carriers from DIAN (mean [SD] age, 38.4 [11.2] years; 137 [54%] female), 571 older adults from ADNI (mean [SD] age, 72.8 [7.3] years; 274 [48%] female), and 318 older adults from HABS (mean [SD] age, 72.4 [7.6] years; 194 [61%] female). Longitudinal increases in WMH volume were greater in individuals with CMBs compared with those without (DIAN: t = 3.2 [P = .001]; ADNI: t = 2.7 [P = .008]), associated with longitudinal decreases in gray matter volume (DIAN: t = −3.1 [P = .002]; ADNI: t = −5.6 [P &amp;lt; .001]; HABS: t = −2.2 [P = .03]), greater in older individuals (DIAN: t = 6.8 [P &amp;lt; .001]; ADNI: t = 9.1 [P &amp;lt; .001]; HABS: t = 5.4 [P &amp;lt; .001]), and not associated with systemic vascular risk (DIAN: t = 0.7 [P = .40]; ADNI: t = 0.6 [P = .50]; HABS: t = 1.8 [P = .06]) in individuals with ADAD and LOAD after accounting for age, gray matter volume, CMB presence, and amyloid burden. In older adults without CMBs at baseline, greater WMH volume was associated with CMB development during longitudinal follow-up (Cox proportional hazards regression model hazard ratio, 2.63; 95% CI, 1.72-4.03; P &amp;lt; .001).Conclusions and RelevanceThe findings suggest that increased WMH volume in AD is associated with neurodegeneration and parenchymal and vessel amyloidosis but not with elevated systemic vascular risk. Additionally, increased WMH volume may represent an early sign of vessel amyloidosis preceding the emergence of CMBs.