Citations

ABSTRACTObjectivesThis study aimed to compared Patient‐Reported Outcomes Measurement Information System (PROMIS) anxiety, depression, and anger item bank among Korean, US and Dutch general population.MethodsBetween December 2021 and January 2022, we surveyed representative Korean participants (N = 2699). Then we compared the mean T‐scores of PROMIS anxiety, depression, and anger full items bank among Korean, US (N = 1696) and the Dutch (N = 1002) populations. Differential item‐functioning (DIF) analyses were also performed. We also compared each score by age group, sex, presence of comorbidities, and general health status.ResultsIn Korean, the mean T‐scores for anxiety, depression, and anger were 45.3 (standard deviation [SD] = 11.6), 48.4 (SD = 11.2), and 44.9 (SD = 12.6), respectively. Among the general population in Korea, patients aged 35–44 years and those with comorbidities had higher anxiety, depression, and anger scores. In the DIF analyses between the US and Korean populations, 28%, 32%, and 45% were flagged for uniform or non‐uniform DIF in anxiety, depression and anger, respectively.ConclusionsConsidering the cultural differences, we recommend using a harmonized approach that includes country‐specific reference values while retaining a standardized core set of items to enable cross‐country comparability.

Abstract Background While serial sampling of glioma tissue is rarely performed prior to recurrence, cerebrospinal fluid (CSF) is an underutilized longitudinal source of candidate glioma biomarkers for understanding therapeutic impacts. However, the impact of key variables to consider in longitudinal CSF samples for monitoring biomarker discovery, including anatomical location and post-surgical changes, remains unknown. Methods Aptamer-based proteomics was performed on 147 CSF samples from 74 patients; 71 of whom had grade 2–4 astrocytomas or grade 2–3 oligodendrogliomas. This included pre- versus post-resection intracranial CSF samples obtained at early (1–16 days; n = 20 patients) or delayed (86–153 days; n = 11 patients) time points for patients with glioma. Paired lumbar versus intracranial glioma CSF samples were also obtained (n = 14 patients). Results Significant differences were identified in the CSF proteome between lumbar, subarachnoid, and ventricular CSF in patients with gliomas. Importantly, we found that resection had a significant, evolving longitudinal impact on the CSF proteome, with distinct sets of proteins present at different time points since resection. Our analysis of serial intracranial CSF samples suggests the early potential for disease monitoring and evaluation of pharmacodynamic impact of targeted therapies, such as bevacizumab and immunotherapies. Conclusions The intracranial glioma CSF proteome serves as a rich and dynamic reservoir of potential biomarkers that can be used to evaluate the effects of resection and other therapies over time. All data within this study, including detailed individual clinical annotations, are shared as a resource for the neuro-oncology community to collectively address these unanswered questions and further understand glioma biology through CSF proteomics.

Abstract Cerebrospinal fluid (CSF) has emerged as a valuable liquid biopsy source for glioma biomarker discovery and validation. CSF produced within the ventricles circulates through the subarachnoid space, where the composition of glioma-derived analytes is influenced by the proximity and anatomical location of sampling relative to tumor, in addition to underlying tumor biology. The substantial gradients observed between lumbar and intracranial CSF compartments for tumor-derived analytes underscore the importance of sampling site selection. Moreover, radiographic features, such as tumor-CSF contact and blood-brain barrier disruption, are critical covariates that may affect biomarker detection and the abundance of plasma-derived analytes in CSF, respectively. Longitudinal intracranial CSF sampling, enabled by access devices like Ommaya reservoirs, may offer a window into treatment response and disease progression, though variability in analyte yield, sample volumes, and the dynamic effects of surgical resection pose challenges. This review critically evaluates the anatomic, radiographic, and longitudinal factors, or “time-space continuum,” that impact glioma CSF biomarker abundance. Practical considerations for longitudinal CSF biobanking, including access device placement and collection, are also reviewed. Key takeaways and recommendations for CSF glioma biomarker discovery and validation are provided as a “hitchhiker’s guide” based on our collective experience, along with resources for investigators aiming to develop CSF biobanking at their institutions.

AbstractBackgroundThe clinical significance of natural and treatment‐emergent antibodies specific for amustaline/glutathione pathogen‐reduced red blood cells (PRRBCs) is not known.Study Design and MethodsA Phase 3, randomized clinical trial of PRRBCs (ReCePI) compared PRRBCs with conventional RBCs in cardiac or thoracic‐aorta surgery. Subjects transfused during and for 7 days after surgery were screened for PRRBC‐specific antibodies at baseline, 28 and 75 days post‐surgery. Subjects with treatment‐emergent antibodies were assessed for evidence of hemolysis. Cryopreserved subject RBC samples were assayed by flow cytometry for circulating PRRBCs using an acridine‐specific (2S197‐2M1) monoclonal antibody, and for human IgG‐coated RBCs. RBC‐surface acridine density was quantitated using a commercial calibrated phycoerythrin (PE)‐bead panel.ResultsFive of 159 (3.1%) PRRBC and zero of 162 conventional RBC recipients developed treatment‐emergent PRRBC‐specific IgG, low titer antibodies detected 26–80 days post‐surgery after exposure to 1–3 PRRBC units, without clinical evidence of hemolysis. DAT and eluate were weak (w+) positive and PRRBC‐specific in one subject. A monocyte monolayer assay (MMA) was non‐reactive in the three subjects with an interpretable result. Flow cytometry demonstrated circulating PRRBCs in all five subjects expressing surface acridine concentrations at the limit of detection (approximately 150–301 PE molecules/RBC) compared with freshly transfused PRRBCs (approximately 7500 PE molecules/RBC). In some samples, loss of surface acridine expression could not be distinguished from clearance of the PRRBCs.DiscussionTreatment‐emergent PRRBC‐specific antibodies with the characteristics of nonclinically significant antibodies were detected in five subjects transfused with PRRBCs. Flow cytometry demonstrated persistent circulating PRRBCs with minimal surface acridine expression. (www.ClinicalTrials.gov Identifier NCT03459287).

The gut–brain axis plays an integral role in maintaining overall health, with growing evidence suggesting its impact on the development of various neuropsychiatric disorders, including depression. This review explores the complex relationship between gut microbiota and glutamate (Glu) regulation, highlighting its effect on brain health, particularly in the context of depression following certain neurological insults. We discuss how microbial populations can either facilitate or limit Glu uptake, influencing its bioavailability and predisposing to neuroinflammation and neurotoxicity. Additionally, we examine the role of gut metabolites and their influence on the blood–brain barrier and neurotransmitter systems involved in mood regulation. The therapeutic potential of microbiome-targeted interventions, such as fecal microbiota transplantation, is also highlighted. While much research has explored the role of Glu in major depressive disorders and other neurological diseases, the contribution of gut microbiota in post-neurological depression remains underexplored. Future research should focus on explaining the mechanisms linking the gut microbiota to neuropsychiatric outcomes, particularly in conditions such as post-stroke depression, post-traumatic brain-injury depression, and epilepsy-associated depression. Systematic reviews and human clinical studies are needed to establish causal relationships and assess the efficacy of microbiome-targeted therapies in improving the neuropsychiatric sequalae after neurological insults.

Background: Total joint arthroplasty (TJA) is increasingly being performed as an outpatient (i.e., same-day discharge) procedure. Postoperatively, orthostatic hypotension or pain-related tachycardia can lead to concerns regarding the hemoglobin (Hgb) level of the patient prior to discharge. The purpose of this study was to prospectively assess the reliability and accuracy of, and patient and nurse satisfaction with, postoperative noninvasive hemoglobin (nHgb) monitoring compared with an invasive serum hemoglobin (iHgb) laboratory draw in the outpatient TJA setting. Methods: We prospectively enrolled 200 patients undergoing outpatient unilateral TJA, of whom 157 were ultimately included in our analysis (94 hips, 63 knees). Postoperatively, both nHgb and iHgb values were obtained at a mean of 36 minutes apart. Surveys were completed by patients and nurses. The strength of the agreement between the 2 Hgb monitoring methods was evaluated with use of the Bland-Altman 95% limits of agreement, concordance correlation coefficient (CCC), and intraclass correlation coefficient (ICC). Receiver operating characteristic curve analyses were performed to investigate the ability of nHgb monitoring to predict an iHgb of <11.2 g/dL (the 5th-percentile iHgb value). Results: The mean preoperative iHgb was 14.2 ± 1.1 g/dL. The mean postoperative iHgb and nHgb values were 13.3 ± 1.5 and 13.3 ± 1.2 g/dL, respectively. The Bland-Altman 95% limits of agreement were −3.2 and +3.1 g/dL, indicating that 95% of patients’ iHgb values are expected to fall between these limits relative to the nHgb value of the patient. The CCC and ICC were both 0.33. An nHgb cutoff value of <12.7 g/dL had 100% sensitivity and 67% specificity for detecting an iHgb of <11.2 g/dL. Patients reported less pain with the nHgb test than with the iHgb test (mean pain score, 0.0 versus 1.8; p < 0.001), and 97% of patients preferred the nHgb test. Following the nHgb test, 73% of responding patients and 83% of responding nurses were “somewhat more reassured” to “significantly more reassured” about same-day discharge. Conclusions: Routine nHgb testing can rapidly screen patients undergoing outpatient TJA for acute anemia prior to discharge. With an nHgb of <12.7 g/dL, there was perfect sensitivity and 67% specificity for detecting an iHgb of <11.2 g/dL. Most patients and nurses felt more reassured about same-day discharge after nHgb monitoring. Level of Evidence: Diagnostic Level II . See Instructions for Authors for a complete description of levels of evidence.

Abstract As the healthcare burden caused by an increasingly aging population rapidly rises, a pressing need exists for innovative geroscience research that can elucidate aging mechanisms and precipitate the development of therapeutic interventions to support healthy aging. The Fifth Annual Midwest Aging Consortium Aging Research symposium, held from April 28 to 30, 2024, was hosted by The Ohio State University in Columbus, Ohio, and featured presentations from investigators across the Midwestern United States. This report summarizes the research presented at the symposium, whose topics included cellular senescence and the aging brain, metabolism and metabolic interventions, nutrition, redox mechanisms and biomarkers, and stress mechanisms. Abstract presentations and short talks highlighted early-stage and young investigators, whereas 2 keynote presentations anchored the symposium. Overall, this symposium showed the robustness of aging research in the Midwest and underscored the advantages of a collaborative approach to geroscience research.

Inconsistency in the calculation of time spent in moderate to vigorous physical activity (MVPA) limits interstudy comparability and interpretation of surveillance data. This study assesses whether combining multiple individual methods results in a more accurate estimate of MVPA, while considering the influence of device brand and wear location. Participants (n = 30, age = 49.2 ± 19.5 years) wore two accelerometers (GENEActiv, ActiGraph) on each wrist during two laboratory visits. Individual classification methods (11 for left wrist, eight for right wrist) estimated minutes of MVPA using three approaches (cut-point, two-regression, and machine learning), two types of input (count and raw), and five epoch lengths (1, 5, 15, 30, and 60 s). The consensus estimate was calculated as the mean or median (due to skew) across all individual estimates. No individual or consensus estimates were statistically equivalent to direct observation (mean 38.2 min), with 81%–95% of individual methods overestimating MVPA. The best-performing individual methods were raw acceleration cut-points, with a bias of −3.2 to 2.4 min across devices and wrists. Correlation coefficients between individual methods and the criterion were .35–.71 for the left and .12–.67 for the right wrist, compared to .65–.70 and .58–.66 for consensus methods, respectively. Correlations between device brands were .23–.99 for individual methods and .70–.86 for consensus methods, while correlations between locations were .55–.86 and .73–.87, respectively. Better methods are required for estimating MVPA from wrist-worn accelerometers given the consistent overestimation of MVPA observed. While a consensus method for wrist-worn data was not able to fully resolve these issues, it improves interwrist or interbrand comparability.