Citations

AbstractBackgroundFew normative data for computerized measures administered in unsupervised remote environments are available. We aimed to determine what variables to include in normative models for remote self‐administered assessments, develop normative data for measures administered through Mayo Test Drive (MTD, a multi‐device remote cognitive assessment platform) and evaluate application of norms.Method1240 adults ages 33‐100 (96% White) from the Mayo Clinic Study of Aging and Mayo Alzheimer’s Disease Research Center met normative sample inclusion criteria that included a concordant Cognitively Unimpaired (CU) diagnosis (3 independent raters all diagnosed CU) and CDR = 0 (see Table 1 for sample characteristics). Raw test scores were converted to normalized scaled scores. We derived regression‐based normative data that adjusted for age, age2, sex and education (base model); alternative models are also provided (age+age2+sex; age+ age2). We evaluated whether additional model terms beyond the base model were needed using an a priori cut‐off of 1% variance improvement in adjusted R2 over and above the base model. We examined rates of low test performance defined as performance below ‐1 SD in independent validation samples (n = 167 concordant CU, n = 64 mild cognitive impairment (MCI), n = 14 dementia). Rates are considered significantly different than expected when 95% confidence intervals (CIs) do not include the expected 14.7% base rate frequency.ResultNo additional potential model terms met our a priori cut‐off for inclusion beyond the base model (see Table 2), including other quadratic and cubic terms or interactions, device type, response input type, potential session interference, and national area deprivation index (ADI available in subset; N = 776). Application of norms showed expected rates of low test performance among CU participants (95% CI includes expected base rate) and significantly greater than expected rates of low test performance for all variables in MCI (e.g., 62.5% for composite) and dementia (e.g., 71.4% for composite; see Table 3).ConclusionTypical normative models appear appropriate for remote self‐administered measures and are sensitive to cognitive impairment. Device type and response input did not explain enough variance to warrant inclusion in normative models but are important for individual level interpretation. Future work will improve representation of individuals from under‐represented groups.

Background A variety of clinically important benchmarks of success (CIBS) have been defined for total shoulder arthroplasty (TSA) to quantify success. However, it is unclear how the preoperative status of the patient influences their likelihood of achieving each CIBS. Questions/purposes (1) What proportion of patients achieve commonly used CIBS after TSA? (2) Is there a relationship between a patients’ preoperative function and their probability of achieving different CIBS? (3) Does there exist preoperative ranges for each outcome measure that are associated with greater achievement of CIBS? Methods We retrospectively queried a multicenter shoulder arthroplasty database for primary anatomic TSA (aTSA) and reverse TSA (rTSA). A total of 2041 aTSAs and 3205 rTSAs were included. The mean ± SD age at time of surgery was 66 ± 9 years for aTSAs and 72 ± 8 years for rTSAs. In all, 51% (1049 of 2041) of aTSAs and 61% (1955 of 3205) of rTSAs were in patients who were women. For aTSAs, osteoarthritis with an intact rotator cuff was the most common preoperative diagnosis (92% [1869 of 2041]). For rTSAs, the most common preoperative diagnoses included rotator cuff tear arthropathy (40% [1280 of 3205]), osteoarthritis with an intact rotator cuff (24% [780 of 3205]), osteoarthritis with a torn rotator cuff (20% [632 of 3205]), and massive rotator cuff tear (10% [309 of 3205]). Outcomes were evaluated at latest follow-up (aTSA 61 ± 36 months, rTSA 47 ± 26 months) and consisted of ROM (abduction, forward elevation, external and internal rotation) as well as the most commonly used outcome scores: the Simple Shoulder Test (SST), Constant score, American Shoulder and Elbow Surgeons (ASES) score, University of California, Los Angeles (UCLA) score, Shoulder Pain and Disability Index (SPADI), and the Shoulder Arthroplasty Smart (SAS) score. The CIBS that we evaluated included the minimum clinically important difference (MCID), substantial clinical benefit (SCB), patient acceptable symptom state (PASS), minimum clinically important percentage of maximal possible improvement (MCI-%MPI), and substantial clinically important percentage of maximal possible improvement (SCI-%MPI). Prosthesis-specific anchor-based CIBS were adopted from prior publications on patients from this database. Multivariable regression was performed to identify the relationship between preoperative outcome measures and achievement of CIBS. Additionally, receiver operating characteristic (ROC) curve analyses were performed to determine whether thresholds in preoperative outcome measures were associated with achieving CIBS. Results For all ROM measures and outcome scores, poorer preoperative ROM was associated with greater odds of achieving the MCID and SCB but lower odds of achieving the PASS. For the SST and the two scores without ceiling effects (the Constant and SAS scores), poorer preoperative outcome scores were associated with greater odds of achieving the MCI-%MPI and SCI-%MPI, but no association was demonstrated for the ASES, SPADI, and UCLA scores. Graphical analysis demonstrated that patients with greater preoperative ROM and outcome scores had a lower probability of achieving the MCID and SCB but a higher probability of achieving the PASS. For outcome scores with known ceiling effects, patients with more favorable preoperative outcome scores were more likely to achieve the MCI-%MPI and SCI-%MPI than the MCID and SCB, respectively. For outcome scores without ceiling effects, patients undergoing aTSA were more likely to achieve the MCID, MCI-%MPI, and the SCI-%MPI than the SCB, but no clear trend was identified for patients undergoing rTSA. On ROC curve analysis, identified thresholds were reasonably accurate (area under the curve > 0.7) for achievement of measures of absolute improvement (the MCID and SCB), but not for absolute postoperative status (the PASS) or relative improvement (the MCI-%MPI and SCI-%MPI). Conclusion While most patients reported being “much better” (aTSA 75%, rTSA 76%) or “better” (aTSA 15%, rTSA 18%) compared with before surgery, 10% of aTSAs and 6% of rTSAs were either “unchanged” or “worse.” Patients’ likelihood of achieving CIBS depends in part on their baseline function and whether success is defined as absolute improvement, absolute postoperative status, or relative improvement. Patients with more favorable preoperative status are more likely to achieve CIBS that evaluate relative improvement (the MCI-%MPI and SCI-%MPI) than absolute improvement (the MCID and SCB). Future studies are needed to determine which individual CIBS or combinations thereof most accurately represent clinically relevant benefit. Level of Evidence Level III, therapeutic study.

ABSTRACTBackgroundPeriodontal disease (PD) is a prevalent, preventable and treatable oral infection associated with substantial morbidity globally. There is little information from population‐representative cohort studies about the sociodemographic, educational and other early life factors that stratify PD risk.MethodsWe used data from the U.S. ‘High School and Beyond’ (HS&B:80) study, which has followed a nationally representative sample of 26,820 people from high school in 1980 through midlife in 2021. Data from the 1980s include information about education, early life circumstances, spatial location and demographic attributes. Data from 13,080 sample members who responded in 2021 include indicators of self‐reported PD diagnosis.ResultsPeople with higher degrees and course grades have a lower risk of midlife PD. Rural adolescents and those who attended private schools are also at lower risk. We find little evidence of heterogeneity in correlates of midlife PD by gender or race/ethnicity.ConclusionsThe quantity and characteristics of people's schooling and their location of residence are associated with midlife PD.

Abstract High-dose methotrexate (MTX) results in high rates of acute kidney injury (AKI), neutropenia, and hepatotoxicity. Glucarpidase is a recombinant enzyme that cleaves MTX, but clinical data supporting its use are scarce. We examined the association between glucarpidase administration and outcomes in adults with MTX-AKI from 28 cancer centers across the United States using a sequential target trial emulation framework. The primary end point was kidney recovery at hospital discharge, defined as survival to discharge with serum creatinine <1.5-fold baseline and without dialysis dependence. Key secondary end points were time to kidney recovery, neutropenia, and transaminitis on day 7, and time to death. Using multivariable logistic and Cox regression models, we compared outcomes in patients who received glucarpidase within 4 days following MTX initiation with those in patients who did not. Among 708 patients with MTX-AKI, 209 (29.5%) received glucarpidase. Overall, 183 (25.8%) had a primary end point event. Glucarpidase receipt was associated with a 2.70-fold higher adjusted odds of kidney recovery (95% confidence interval [CI], 1.69–4.31) compared with no glucarpidase receipt. Patients treated with glucarpidase also had faster time to kidney recovery (adjusted hazard ratio [aHR], 1.88; 95% CI, 1.18–3.33) and lower risks of grade ≥2 neutropenia (adjusted odds ratio [aOR], 0.50; 95% CI, 0.28–0.91) and grade ≥2 transaminitis (aOR, 0.50; 95% CI, 0.28–0.91) on day 7. There was no difference in time to death (aHR, 0.76; 95% CI, 0.49–1.18). These data suggest glucarpidase may improve both renal and extrarenal outcomes in patients with MTX-AKI.

BACKGROUND Posttraumatic retroclival hematomas are rare pathologies among pediatric patients and can result in cranial nerve palsies. The authors sought to survey the literature and characterize the risk factors, treatment considerations, and overall outcomes for pediatric patients experiencing posttraumatic retroclival hematomas. OBSERVATIONS A search of the Ovid Embase, Scopus, PubMed, and Web of Science databases from January 1986 to May 2024 was performed following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Additionally, the authors report a novel case of pediatric retroclival hematoma. The systematic review identified 41 eligible articles describing 64 individual cases of posttraumatic clival/retroclival hematoma in pediatric patients. The incidence of abducens nerve palsy in the setting of posttraumatic retroclival hematoma was 40%, and the rate of complete recovery of abducens nerve function was 73%. Analyses revealed that a higher initial Glasgow Coma Scale (GCS) score correlated with general neurological recovery (p < 0.05). However, no significant difference was found in GCS scores between patients with complete and those with incomplete abducens nerve recovery. LESSONS There is a high rate of spontaneous recovery of abducens nerve function in patients with abducens palsy in the setting of posttraumatic retroclival hematoma. While initial GCS scores can predict general neurological recovery, factors influencing abducens nerve palsy resolution remain unclear. https://thejns.org/doi/10.3171/CASE24474

Background: Mismatch between osteochondral allograft (OCA) donor and recipient sex has been shown to negatively affect outcomes. This study accounts for additional donor variables and clinically relevant outcomes. Purpose: To evaluate whether donor sex, age, donor-recipient sex mismatch, and duration of graft storage affect clinical outcomes and failure rates after knee OCA transplantation. Study Design: Cohort study; Level of evidence, 3. Methods: Patients undergoing knee OCA transplantation between 2003 and 2018 were prospectively followed. Inclusion criteria consisted of primary OCA transplantation and minimum 2-year follow-up. Patient descriptive data and allograft donor sex, age, and graft storage time before implantation were collected. Patients were evaluated for reoperation, failure, and achievement of clinically significant outcomes for International Knee Documentation Committee scores. Reoperation was defined as subsequent surgical intervention of the transplanted allograft, including second-look arthroscopy for graft evaluation, debridement, and loose body removal. Failure was defined as revision of the primary OCA transplantation or conversion to arthroplasty. A Kaplan-Meier curve determined cumulative survivability of OCA transplantations, and log-rank testing was used to compare survivorship between groups. Stepwise regression analysis was utilized to evaluate associations between donor variables and achievement of clinically significant outcomes, reoperation, and failure. Results: A total of 372 patients undergoing OCA transplantation were included and followed for a mean 5.4 years (SD, 2.7; range, 2.0-16.3). Isolated OCA transplantation was performed in 45% of cases (169/372). A mismatch in donor and recipient sex was present for more female patients (90%) than male patients (10%; P < .001). Those who had a sex-mismatched graft more frequently underwent concomitant tibial tubercle osteotomy ( P = .034). When controlling for patient sex, no other differences were seen between groups matched and mismatched by sex. Univariable and multivariable analysis found no significant difference in survival free from reoperation or failure on the basis of donor-recipient sex mismatch, donor age, or graft storage time before implantation. Conclusion: In contrast to previous historical data, no donor variables were associated with inferior clinical outcomes in patients who underwent OCA transplantation. These data can help inform graft selection, expedient recipient selection, and outcome optimization after OCA transplantation.

Purpose To characterize variation in the value of hip arthroscopy for femoroacetabular impingement and explore associations between value and patient‐specific demographic characteristics, comorbidities, preoperative patient‐reported outcome measures (PROMs), and intraoperative variables. Methods We included all patients aged 18 years or older who underwent primary arthroscopic acetabular labral repair or debridement between 2015 and 2020 with minimum 2‐year follow‐up. The exclusion criteria were hip dysplasia, advanced hip osteoarthritis (TÖnnis grade >1), or unreconcilable documenting errors. Value was calculated by dividing 2‐year postoperative International Hip Outcome Tool 33 scores by time‐driven activity‐based costs. To protect the confidentiality of internal hospital cost data, the study average for value was normalized to 100. Multivariable linear mixed‐effects models were used to identify factors underlying variation in value. Results This study included 161 patients. There were 76 women (47.2%) and 85 men, with a mean age of 36.0 years (standard deviation [SD], 10.9 years) and mean body mass index (BMI) of 25.8 (SD, 4.3). Most patients were white (92.5%), were not Hispanic (93.8%), and were commercially insured (92.5%). Preoperatively, 57.1% of hips were classified as Tönnis grade 1 (57.1%) whereas the remainder were grade 0. The normalized value of hip arthroscopy ranged from 25.4 to 216.4 (mean ± SD, 100 ± 38.4), with a 3.0‐fold variation between patients in the 10th and 90th percentiles. Higher value was significantly associated with Tönnis grade 0 (12.2‐point increase, P = .025), no prior contralateral hip arthroscopy (17.3‐point increase, P = .039), higher preoperative PROMs (0.52‐point increase per 1‐unit increase, P < .001), and no bone marrow aspirate concentrate or microfracture (33.8‐point increase, P < .001). Value was also significantly associated with osteoplasty type and labral treatment technique ( P < .05 for both). In contrast, operative year, age, sex, BMI, race, ethnicity, Outerbridge grade, and American Society of Anesthesiologists score were not independently associated with value. A model incorporating these factors as fixed effects and the surgery center as a random effect explained 42.3% of the observed variation in value. Sensitivity analyses revealed that value drivers may vary slightly across PROMs. Conclusions This study revealed wide variation in the value of hip arthroscopy that was most strongly explained by osteoplasty type, labral management technique, and preoperative PROMs. In contrast, patient demographic characteristics such as age, sex, and BMI contributed minimal independent variability. Level of Evidence Level IV, economic and decision analysis.

Purpose of review Once considered to have only local influences on the gut mucosa, short-chain fatty acids (SCFAs) now appear to have a much wider anti-inflammatory, immune-modulating, systemic effect. This article reviews recent evidence to suggest a much wider clinical application of this valued dietary substrate. Recent findings SCFAs act systemically through stimulation of G protein receptors (GPRs) and inhibition of histone deacetylases (HDACs). SCFAs cause appetite suppression, reduce systemic inflammation, improve insulin sensitivity, increase energy expenditure, promote mitochondrial function, stimulate satiety, reduce blood pressure, and improve cognitive function from various neurologic maladies. Summary Dietary strategies should be implemented to provide this beneficial substrate across a wide spectrum of disease conditions. Use of prebiotic fiber or liquid supplements containing high SCFA-producing organisms should be considered as therapeutic targets for multiple metabolic, immunologic, and neurodegenerative diseases.

AbstractBackgroundAlzheimer’s disease (AD) is a devastating neurodegenerative disorder with few therapies to treat, mitigate or prevent its onset. Understanding of this disease is predominantly based on research in non‐Hispanic Whites (NHW) although AD disproportionately affects African Americans (AA) and Latin Americans (LA), underrepresented in AD research. To address this knowledge gap, the Accelerating Medicine Partnership for Alzheimer’s Disease (AMP‐AD) Diversity Working Group was launched to generate multi‐omics data from post‐mortem brain tissue from donors of predominantly AA and LA descent. Here, we focus on genomic and transcriptomics measures, made available through the AD Knowledge Portal (ADKP).MethodBrain tissue from dorsolateral prefrontal cortex (DLPFC), caudate nucleus (CN), superior temporal gyrus (STG) and temporal pole (TP) regions of AA (N = 299), LA (N = 344) and NHW (N = 532) donors was obtained through Mayo Clinic, Mt. Sinai School of Medicine, Emory, Columbia, Rush Alzheimer’s Disease Center, Banner Sun Health, and 1Florida. DNA extracted from DLPFC tissue samples (n = 641) was utilized for whole genome sequencing (WGS) at New York Genome Center (NYGC). RNAseq of 2,224 samples was conducted either at Mayo, Rush or NYGC. Sequencing reads were processed through GenomeGPS and MAPRseq pipelines for WGS and RNAseq data, respectively. Following quality control (QC), RNAseq data was normalized and assessed for sources of variation (SOV). Integration of WGS and RNAseq data to perform comparative eQTL analysis across multi‐ethnic populations and brain regions is ongoing.ResultWGS data for 621 donors, and RNAseq data generated at Mayo (n = 1,136 samples), Rush (n = 627), and NYGC (n = 779) sequencing centers, were deposited to the ADKP. Consensus processing of RNAseq data revealed site, sex, race/ethnicity, RIN, AD diagnosis, age at death and/or library batch as SOV across various sites and brain regions. Principal component analysis of gene expression measures revealed no major stratification by disease or brain region. Accompanying clinical metadata of donors have been distributed through ADKP.ConclusionThese multi‐omics data made available to the research community is expected to be an initial step towards bridging our data and knowledge gap to elucidate conserved and distinct AD related pathways across these underrepresented at‐risk populations.

AbstractBackgroundFew normative data for computerized measures administered in unsupervised remote environments are available. We aimed to determine what variables to include in normative models for remote self‐administered assessments, develop normative data for measures administered through Mayo Test Drive (MTD, a multi‐device remote cognitive assessment platform) and evaluate application of norms.Method1240 adults ages 33‐100 (96% White) from the Mayo Clinic Study of Aging and Mayo Alzheimer’s Disease Research Center met normative sample inclusion criteria that included a concordant Cognitively Unimpaired (CU) diagnosis (3 independent raters all diagnosed CU) and CDR = 0 (see Table 1 for sample characteristics). Raw test scores were converted to normalized scaled scores. We derived regression‐based normative data that adjusted for age, age2, sex and education (base model); alternative models are also provided (age+age2+sex; age+ age2). We evaluated whether additional model terms beyond the base model were needed using an a priori cut‐off of 1% variance improvement in adjusted R2 over and above the base model. We examined rates of low test performance defined as performance below ‐1 SD in independent validation samples (n = 167 concordant CU, n = 64 mild cognitive impairment (MCI), n = 14 dementia). Rates are considered significantly different than expected when 95% confidence intervals (CIs) do not include the expected 14.7% base rate frequency.ResultNo additional potential model terms met our a priori cut‐off for inclusion beyond the base model (see Table 2), including other quadratic and cubic terms or interactions, device type, response input type, potential session interference, and national area deprivation index (ADI available in subset; N = 776). Application of norms showed expected rates of low test performance among CU participants (95% CI includes expected base rate) and significantly greater than expected rates of low test performance for all variables in MCI (e.g., 62.5% for composite) and dementia (e.g., 71.4% for composite; see Table 3).ConclusionTypical normative models appear appropriate for remote self‐administered measures and are sensitive to cognitive impairment. Device type and response input did not explain enough variance to warrant inclusion in normative models but are important for individual level interpretation. Future work will improve representation of individuals from under‐represented groups.