Citations

Abstract Background Takayasu arteritis (TA) is a rare large-vessel vasculitis that can involve pulmonary arteries, potentially leading to pulmonary hypertension (PH). Noninvasive evaluation by echocardiography is often used, but its reliability in confirming and characterizing PH in TA is unclear. We investigated the role of invasive hemodynamic testing in TA patients with suspected PH. Methods We retrospectively identified 10 patients with TA meeting 2022 ACR criteria and suspected PH based on symptoms and/or echocardiography; all underwent echocardiography followed by right heart catheterization (RHC).PH was defined as mean pulmonary artery pressure (mPAP) >20 mmHg. PH was classified as pre-capillary (pulmonary artery wedge pressure [PAWP] ≤15 mmHg), post-capillary (PAWP >15 mmHg), or combined (PAWP >15 mmHg with elevated pulmonary vascular resistance). Echocardiographic parameters were collected where available, along with invasive hemodynamics, cardiac biomarkers (BNP/NT-proBNP), inflammatory markers (ESR, CRP), NYHA functional class, and outcomes. Results Median age was 44 years (range 18-58), and 90% were female. Based on invasive hemodynamics, pre-capillary PH was present in 5 patients, combined pre-/post-capillary PH in 3, and isolated post-capillary PH in 2. Median mPAP was 38 mmHg (IQR 30-55), median pulmonary vascular resistance 3.5 Wood units (IQR 2.3-8.7), and median PAWP 15 mmHg (IQR 8-24). Echocardiography frequently underestimated disease severity. Several patients with absent or low tricuspid regurgitation velocity (≤1.0 m/s), where measurable, demonstrated severe pre-capillary PH on RHC, including pulmonary vascular resistance >6 Wood units. Among patients with available data, NT-proBNP levels ranged from 59 to 51,968 pg/mL, and inflammatory markers varied widely (CRP <0.3 to 107.9 mg/L). Among patients with available NYHA data, most were class II-III. Conclusions In this TA cohort, RHC was essential to confirm and phenotype PH, which was present in the majority of those with suspected PH. Echocardiography alone often underestimated or misclassified PH in TA - in one case missing severe pre-capillary PH due to an absent TR signal, and in another failing to discern elevated left-heart filling pressure. Invasive assessment prevented missed diagnoses and misclassification, ensuring appropriate management of TA-associated PH This abstract is funded by: None

ABSTRACT Prior surveys of chronic automated red blood cell exchange (RCE) for patients with sickle cell disease (SCD) have identified considerable procedural variability, especially with the use of isovolemic hemodilution red blood cell exchange (IHD‐RCE). We conducted a survey of chronic RCE practices among American Society for Apheresis (ASFA) members to identify opportunities for practice harmonization and future studies. The ASFA SCD Research Subcommittee developed a 72‐item survey of chronic RCE practices, with a focus on IHD‐RCE. The survey was validated internally and distributed by email to all ASFA members from September 2024 to February 2025. One survey response from each institution was retained for data analysis. Descriptive statistics were performed. Sixty‐two survey responses, including three from international institutions, were retained for analysis. Sixty‐one percent of respondents (38/62) reported using at least one fixed RCE target, with end hematocrit being the most common fixed parameter (40%, 25/62), followed by fraction of cells remaining (31%, 19/62) and hemoglobin S% (27%, 17/62). Most respondents (60%, 37/61) performed IHD‐RCE at their institution, though other details such as the minimum hematocrit, exclusion criteria, and response to adverse effects were variable. Consistent pre‐ and post‐RCE laboratory monitoring practices were reported. Consistent with earlier surveys, procedural variability in chronic RCE practices for patients with SCD is observed. This highlights opportunities to compare outcomes where practice variability exists. Consensus guidelines based on institutional practices with optimal outcomes should be developed.

Aims Reliable assessment of joint stiffness is essential for studying arthrofibrosis in preclinical animal models. This study presents a new dedicated biomechanics device for measuring knee stiffness in mouse, rat, and rabbit models of arthrofibrosis, with the aim of validating its performance and comparing it to a previously validated device. Methods The new system integrates a torque load cell, stepper motor, and absolute encoder in a through-hole, unified configuration for precise continuous torque-angle measurement, with custom limb brackets ensuring species-specific alignment at the joint’s centre of rotation. To validate this device and compare it to a previously validated device, arthrofibrosis was induced using established models of extra-articular immobilization in mice and intra-articular violation with immobilization in rats and rabbits, followed by defined remobilization periods. Torque-angle curves were recorded ex vivo across species-specific torque ranges, and measurement variability between the new and a previous validated device was statistically compared using Brown-Forsythe’s test. Results The onset of hyperextension in contralateral limbs occurred at mean angles of 152.4° (mice), 154.4° (rats), and 152.8° (rabbits), and at maximum torque, mean flexion angles were 79.2°, 87.3°, and 140.5°, respectively. No significant differences in measurement variability were observed between devices across all species. Conclusion These findings demonstrate that our new device provides reproducible torque-angle data while maintaining the statistical robustness of the previous device and offering improved mechanical design and operational standardization. By enabling standardized, cross-species joint stiffness quantification, this platform improves cross-study comparability and strengthens the translational reliability of preclinical arthrofibrosis research. Cite this article: Bone Joint Res 2026;15(6):716–725.

ABSTRACT The coexistence of obesity and insulin resistance is associated with elevated plasma amino acid concentrations. However, it remains unclear whether adiposity or insulin resistance is the stronger determinant of plasma amino acid dysregulation in this setting. Twenty-two adults (10 women, 12 men) spanning a broad range of body mass index (BMI) and insulin resistance underwent a 75-g oral glucose tolerance test (OGTT) after an overnight fast. Plasma glucose, insulin, and amino acid concentrations were measured serially, and insulin resistance/sensitivity was estimated from OGTT-derived glucose and insulin responses, using the homeostasis model assessment of insulin resistance (HOMA-IR) and the Matsuda insulin sensitivity index (Matsuda-ISI). Principal component analysis (PCA) of fasting plasma amino acid concentrations showed no clear separation by obesity or insulin resistance classifications. In contrast, PCA of OGTT-stimulated plasma amino acid concentrations revealed clearer clustering by BMI, fat mass, and waist circumference, whereas separation by HOMA-IR and Matsuda-ISI was less distinct. Importantly, regression analyses showed that BMI, fat mass, and waist circumference were significant predictors of OGTT-stimulated, but not fasting, amino acid responses, with waist circumference accounting for the greatest proportion of the variance in branched-chain amino acid responses during the OGTT (R 2 = 0.54). In conclusion, measures of adiposity, particularly total fat mass and waist circumference, accounted for a greater proportion of the variance in plasma amino acid responses under physiologically stimulated conditions than indices of insulin resistance. These findings support the view that plasma amino acid concentrations reflect adiposity-related metabolic alterations more strongly than insulin resistance.

ABSTRACT Background In healthy individuals, exercise and amino acid availability act synergistically to stimulate muscle anabolism. However, this interaction may be impaired in individuals with obesity. Objective We examined whether acute aerobic exercise alters amino acid-stimulated muscle protein synthesis during immediate postexercise recovery in adults with obesity. Methods Sixteen sedentary adults with a body mass index >30 kg/m 2 underwent a stable-isotope tracer infusion to measure mixed-muscle protein fractional synthesis rate (FSR) in the basal/fasted state and during an amino acid infusion, either with or without prior aerobic exercise. Participants were randomly assigned to receive either amino acid infusion alone (AA) or 45 min of cycling exercise at ∼65% heart rate reserve immediately before amino acid infusion (EX + AA). Results Amino acid infusion increased muscle protein FSR in the AA group ( P < 0.0001) but not in the EX + AA group ( P > 0.05), and the amino acid-stimulated increase in FSR was 78% lower in EX + AA than in AA ( P < 0.01). The amino acid infusion increased ( P < 0.05) plasma amino acid concentrations in both groups. However, during the amino acid infusion, plasma concentrations of essential and branched-chain amino acids, including leucine, were lower in EX + AA than in AA ( P < 0.05). Moreover, across participants, absolute changes in muscle protein FSR were positively associated with plasma leucine concentrations during the amino acid infusion ( P < 0.05). Conclusions These findings show that, in individuals with obesity, acute aerobic exercise markedly attenuates amino acid-stimulated muscle protein synthesis during early postexercise recovery. These findings have important implications for designing nutritional strategies to optimize muscle anabolism in this population.

Abstract Spatial transcriptomics has been widely applied to study the spatial distribution of cell types, cell states, and specific gene expression in tissue samples. However, we show that there is a prevalent transcript leakage problem in spatial transcriptomics data, where transcripts expressed by a cell diffuse to its neighborhood and are recurrently detected in the nearby cells. By analyzing published data sets, we show that this problem is general across data produced from different tissues and different species using different imaging-based and sequencing-based spatial transcriptomics platforms. It affects both upstream tasks such as expression quantification as well as downstream tasks such as cell-type annotation and detection of spatially-dependent gene expression. To tackle the transcript leakage problem, we propose a reference-free Bayesian model-based method, DeLeakage, which cleans up the data much more effectively than existing denoising methods. DeLeakage also improves cell-type annotation and avoids false detection of spatially dependent expression.

Importance Currently, there are no standardized outcome domains or measures in clinical trials for facial aging. Heterogeneity in outcome domains and measurement instruments across clinical trials creates difficulty in directly comparing interventions, determining superior therapies, and developing high-quality meta-analyses. Objective To develop a core outcome set (COS) of essential domains to be reported in clinical trials evaluating the efficacy of interventions for facial aging. Evidence Review PubMed/Medline, Embase, Cochrane Central Register of Controlled Trials, and CINAHL were searched from September 2005 to September 2015. An updated search of the same databases was performed from September 2015 to February 2026. Studies were included if (1) they were randomized clinical trial or controlled clinical trial in design, (2) they assessed the efficacy or safety of an intervention for facial aging, (3) they were published in English, and (4) they involved human participants. Complementary sources, including patient interviews, were used to capture further relevant outcomes. Two rounds of Delphi surveys, followed by consensus meetings, were used to identify outcome domains considered most important by both patient and physician stakeholders. Findings The final COS consists of 6 outcome domains: (1) overall convenience of treatment; (2) time to return to normal work and social activity; (3) overall assessment of focused area of treatment (at the point in time when treatment is expected to provide peak benefit); (4) duration of treatment effect; (5) severity of persistent local or systemic adverse events, including pigmentary change, skin texture change, delayed healing, scarring, and serious adverse events; and (6) patient satisfaction with treatment. Conclusions and Relevance The 6 outcome domains identified through a Delphi consensus are recommended for reporting in future facial aging trials to ensure that outcomes that matter most to patients and clinicians are measured and that results are comparable across interventions.

Objective: Characterize pathogenic variants, rates of mosaicism, genetic testing yield, and disease severity among patients with NF2-related schwannomatosis dichotomized by diagnosis before or after the age of 30. Study design: Retrospective analysis. Setting: Tertiary referral center multidisciplinary NF2 clinic from 2021 to 2024. Patients: Patients with NF2-related schwannomatosis. Intervention: Next-generation sequencing. Main outcome measure: Rates of mosaicism, genetic testing rates and yield, and overall disease severity by tumor burden. Results: From 2021 to 2024, there were 32 patients ≥30 years of age and 39 patients diagnosed at younger ages. Patients diagnosed ≥30 years exhibited decreased likelihood of receiving genetic testing (53% vs. 85%; P =0.009) and decreased genetic yield (defined as identification of a pathogenic genetic variant in those undergoing testing; 65% vs. 85%; P =0.20). Both age groups demonstrated similar rates of pathogenic variant type with loss-of-function being the predominant variant detected in 73% vs. 67%, for ≥30 vs. <30 years of age; P =0.90. Those ≥30 years harbored fewer number of average anatomic regions involved by tumor (2.3 vs. 3.4; P <0.001) and decreased total number of tumors (7 vs. 12; P <0.001). Conclusions: Patients diagnosed with NF2-related schwannomatosis at age ≥30 years exhibited reduced disease severity compared with those diagnosed at a younger age despite harboring similar distributions of genetic pathogenic variants inclusive of loss-of-function pathogenic variants. These observations emphasize the importance of considering patient age in addition to genetic testing for diagnostic framing tailored to patients’ biology and clinical context to optimize care in the setting of NF2-related schwannomatosis.

Shear wave elastography generates shear waves with an acoustic radiation force to obtain estimates of the shear wave speed. Shear wave elastography often utilizes time-of-flight calculations that apply cross-correlations or time-to-peak methods to obtain estimates of the shear wave speed in the time-domain. However, these time-domain methods fail to consider the effect of dispersion caused by the shear viscosity, which can introduce substantial errors into estimates of the shear wave speed. To solve this problem, a new viscoelastic method for estimating shear wave parameters in the time-domain is introduced. The performance of the new method, which is applied to shear wave particle velocity waveforms, is established by evaluating a simulated three-dimensional viscoelastic Green's function model for shear waves in the time-domain. Results show that the new viscoelastic time-domain method is applicable to locations outside of the push beam region at the focal depth and throughout a two-dimensional plane. The results also indicate that estimates of the shear wave speed are either comparable to or significantly improved relative to values obtained from cross-correlations while simultaneously providing estimates of the shear viscosity in the time-domain.