Citations

Abstract Background Prior studies of Alzheimer's disease (AD) biomarker disclosure have answered important questions about individuals’ experiences learning amyloid results. In comparison, the experiences of individuals performing AD biomarker disclosure have been under characterized. The present study examines the clinician experience disclosing amyloid positron emission tomography (PET) results within the Alzheimer's Disease Neuroimaging Initiative's ADNI‐4 study. Methods The ADNI‐4 longitudinal cohort study includes a pragmatic process for amyloid PET disclosure for participants across the cognitive spectrum. Disclosing clinicians complete a short questionnaire after each disclosure session, reporting on the visit length, the clinician's rating of participant and study partner understanding and emotional reactions, topics discussed, challenges, assessment of the visit overall, and any feedback about the process. Results Across the first 100 disclosures (48 cognitively normal, 35 Mild Cognitive Impairment (MCI), 17 dementia) in ADNI‐4, visits lasted an average of 29.4 minutes (SD 13.9, range 10‐90). Most cognitively impaired participants had a loved one present at the disclosure visit (dementia 94%, MCI 80%) but the majority of cognitively normal participants (73%) did not. Clinicians rated understanding of the result as adequate for all study partners and the vast majority (94%) of participants. Clinicians reported feeling “very confident” in their ability to assess readiness to receive result (70%), disclose (73%), and answer questions (77%). Clinicians rated all visits as “good” or better, with two‐thirds (65%) rated as “excellent.” Frequently discussed topics included meaning of result (99%), other risk factors (72%), and emotional impact of result (49%). Stigma and discrimination were rarely discussed, coming up in 12% and 3% of disclosure sessions, respectively. Challenges were infrequent (7%) and primarily included desire for additional information and challenges related to the participant's impairment. Clinicians provided the study team feedback about the disclosure process for 25% of disclosure visits. Comments included the desire for additional information or resources, positive feedback, and the importance of the study partner. Conclusions Clinicians disclosing amyloid PET results in ADNI‐4 report high confidence, adequate participant and study partner understanding, and few challenges. These data from clinicians, in combination with participant data, will inform future disclosure practices in both research and care.

Abstract Background Frontotemporal dementia (FTD) with right anterior temporal lobe (RATL) predominant atrophy is an emerging area of interest. Recent findings by the International Working Group (IWG) have identified this subtype as having a distinct clinical profile within the FTD spectrum (Ulugut et al., 2024, A&D). However, its genetic and pathological underpinnings remain unexplored in large, multicultural cohorts. Methods Retrospective analyses encompassing clinical, genetic, pathological, and neuroimaging data from 23 IWG sites across 13 countries in Asia, Middle East, Europe, North and South America were conducted. The study included 444 patients with FTD exhibiting predominant RATL atrophy. Results Genetic screening was performed on 51% ( n = 225) of the cohort for at least the major frontotemporal lobar degeneration (FTLD) mutations including microtubule‐associated protein tau ( MAPT ), progranulin ( GRN ), and chromosome 9 open reading frame 72 ( C9orf72 ), or dementia panels encompassing extended sets of genes. Of these, 81% were sporadic, showing negative results for the screened genes and a modified Goldman Score of ≥ 3, indicating a negative family history for dementia. The MAPT mutation was the most common genetic variant, identified in 7% of the screened cases (Figure 1). Pathological confirmation was available for 63 patients. Among the sporadic cases, transactive response DNA‐binding protein 43 type C (TDP‐C) pathology was most prevalent (60%, n = 32), while tau‐MAPT pathology was most common in the genetic cases (38%, n = 16). Fifteen cases did not fit neatly into genetic or sporadic categories, displaying heterogeneous pathologies (Figure 2). At the initial visit, compared to genetic cases, patients with TDP‐C pathology were older, and more frequently exhibited semantic deficits, with less frequent attention difficulties and executive dysfunction. No differences were observed in sex distribution, symptom duration or disease severity between genetic and sporadic TDP‐C cases. However, left handedness was more common in TDP‐C cases (14%) compared to genetic cases (5%). Conclusion While FTD with RATL atrophy primarily appears sporadic, a significant proportion of cases exhibit genetic variants. These sporadic and genetic subtypes display distinct neuropathological features and clinical manifestations. Given the implications for therapeutic strategies, precise clinical and molecular subtyping is critical for enhancing patient management and ensuring appropriate enrollment in clinical trials.

Abstract Background Self‐administered and remote digital cognitive assessments provide a scalable method for screening and longitudinal cognitive monitoring. Mayo Test Drive (MTD) is one such assessment with previously demonstrated usability, reliability, validity and multi‐device compatibility. MTD includes a computer‐adaptive word list memory test (Stricker Learning Span) and a measure of processing speed/executive functioning (Symbols Test) that combine to provide an MTD Composite. This study aimed to develop a conditional normative model predicting longitudinal cognitive change for MTD, and to validate the model in two independent samples of cognitively unimpaired (CU) and mild cognitive impairment (MCI)/dementia (DEM) participants. Method 1355 CU participants at initial MTD assessment with 2‐4 consecutive MTD assessments every 7.5 months comprised the development dataset. Linear mixed effects models were used to construct a conditional normative model for MTD assessments 2‐4. The baseline model was chosen a priori , consisting of age, sex, education, baseline score, number of assessments, and time. Device type, race, and baseline score by time interactions were also considered. Variables were only added if a >1% increment in r‐squared was observed. The models were externally validated in 113 CU and 51 MCI/DEM patients. Following model development, the data were updated and additional follow‐up MTD assessments were added for many participants, including the addition of additional CU validation data at test 3 ( N = 126) and 4 ( N = 279). T‐tests compared observed and predicted differences and residual z‐scores between development and validation at each follow‐up assessment. Result Table 1 presents demographic variables. No additional variables increased the r‐squared by >1%. The final models are presented in Table 2. Age, baseline score, sex, and education were significant. Residual z‐scores were not significantly different between CU development and CU validation cohorts, indicating observed scores were in line with model predicted scores. Residual z‐scores were significantly worse among MCI/DEM compared to CU development in 11/12 comparisons (Figure 1), indicating observed scores were below model predicted expectations and implying sensitivity to longitudinal cognitive decline. Conclusion These longitudinal normative models can be used to identify individuals with follow‐up scores outside of expected predicted ranges, signifying abnormal longitudinal cognitive decline.

Abstract Background Amyloid related imaging abnormality edema (ARIA‐E) occurs in about 19% of individuals with autosomal dominant Alzheimer disease (ADAD) treated with an anti‐amyloid‐b monoclonal antibody (Salloway et al., 2021). In a previously reported case, ARIA‐E appeared to colocalize with decreases in PiB‐PET uptake (Joseph‐Mathurin, Llibre‐Guerra, et al, 2022), suggesting an association between amyloid‐b (Aβ) removal and ARIA‐E. Here, we compare longitudinal neuroimaging and corresponding neuropathology in an ADAD individual treated with gantenerumab, who experienced multiple ARIA‐E episodes as sulcal effusions that resolved by the end of the four‐year trial. Methods PiB‐PET and MRI were collected pre‐ and post‐randomization (2 and 4 years). The participant consented to brain donation, which was received a year after trial completion. Four tissue samples were taken from the location of the ARIA‐E in the parieto‐occipital left hemibrain as identified by MRI (one block contained the sulcus affected by ARIA‐E; the rest of the coronal section was captured in the remaining three blocks). Area fractions (AFs) of Aβ (10D5 immunohistochemistry (IHC)), tauopathy (PHF1), microglia (Iba1), and astrocytes (GFAP) in one sulcal region of interest (ROI) from each block and PiB‐PET SUVRs of corresponding ROIs were extracted ( n = 4, Figure 1). Additionally, we included PiB‐PET SUVRs corresponding to ARIA‐E findings observed in the right hemisphere at baseline, two‐year, and four‐year visits ( n = 6). Results Overall PiB‐PET uptake increased during the first two years (before ARIA‐E) and decreased during the last two years (including ARIA‐E episodes) (0.03±0.05 vs. ‐0.04±0.04 SUVR/year, p ‐value=0.01, Figure 2). The decrease seemed more pronounced in ARIA‐E ROIs versus normal‐appearing sulcus ROIs (‐0.05±0.04 vs. ‐0.02±0.03 SUVR/year). Lower PiB uptake at last visit appeared associated with lower Aβ AF (estimates=0.03±0.01, p ‐value=0.07). The ARIA‐E ROI had an Aβ AF of 0.009 while normal‐appearing sulcus ROIs had a mean of 0.02+0.003 (Figure 3). AFs for tauopathy, microglia, and astrocytes were within the range of those of normal‐appearing sulcus ROIs, suggesting an Aβ‐specific effect, although unexamined markers may play a role. Conclusions Our preliminary findings indicated that ARIA‐E is associated with longitudinal PiB‐PET decrease and Aβ AF, supporting the link between ARIA‐E, changes in PiB‐PET, and local Aβ removal observed at autopsy. Funding : K01AG080123; U01AG042791; R01AG046179; R01AG053267

Study Design. Modified Delphi consensus process Objective. To establish a standardized, consensus-driven definition for postoperative spine infection (PSI) for research, diagnosis, and management. Summary of Background Data. Postoperative infection is a devastating and common complication following spine surgery. Rates of PSI in the literature range from 0% to over 20% depending on surgical indication and invasiveness. Despite the implications of PSI, there is no universally accepted diagnostic standard or consensus definition for infection following spine surgery, hindering research and treatment of this challenging clinical condition. Methods. A multispecialty workgroup convened by the Musculoskeletal Infection Society (MSIS) conducted a systematic literature review. Using data from the systematic review, an expert panel completed a modified Delphi process to achieve consensus. The panel included nine fellowship-trained, board-certified physicians with expertise in infectious diseases, orthopaedic and neurologic spine surgery, and musculoskeletal radiology. Iterative rounds focused on criterion selection, importance ranking, categorical grouping, and final constellation development for PSI diagnosis. Consensus was defined as a 2/3 majority, with a target of 100%. Results. The workgroup achieved 100% consensus on a new PSI definition, which incorporates six clinical domains: wound features, microbiology, imaging, inflammatory biomarkers, intraoperative findings, and histology. A single microbiological stand-alone criterion—identification of a phenotypically indistinguishable organism from two or more deep operative site specimens—was established as pathognomonic for postoperative spine infection. Additional primary and secondary supporting criteria were defined, with specific combinations required to classify cases as definite or probable PSI. Final definitions were ratified by the boards of MSIS and the European Bone & Joint Infection Society (EBJIS) Conclusion. This consensus-based definition provides a standardized framework for diagnosing postoperative spine infection, facilitating research and clinical management. The criteria balance sensitivity and specificity across diverse clinical scenarios and represent the first multispecialty, society-endorsed definition for PSI.

Introduction: Adult hepatitis B vaccination coverage in the United States remains low despite updated national recommendations supporting universal adult immunization. Many adults remain unaware of their susceptibility to hepatitis B virus (HBV) infection. This quality improvement (QI) study evaluated a stepwise “Offer–Offer–Test–Vaccinate” workflow designed to improve hepatitis B vaccine uptake among vaccine-hesitant adults in a primary care setting. Methods: This retrospective QI study was conducted at a single primary care clinic in Rochester, Minnesota. Adult patients (≥19 years) seen between October 1, 2022, and October 1, 2024, were routinely offered hepatitis B vaccination during rooming. Two participating physicians implemented an enhanced workflow in which patients who declined vaccination were counseled and then offered serologic screening using the 2023 CDC-recommended triple panel (HBsAg, anti-HBs, and total anti-HBc). Patients with negative serology were notified via the patient portal and reoffered vaccination along with a link to the CDC Vaccine Information Statement. The primary endpoint was initiation of the hepatitis B vaccine series following receipt of negative serology results. Preliminary series-completion data through October 1, 2025, were also assessed. Results: Among 501 eligible adults, 104 (20.8%) accepted vaccination at the initial offer. Of the 397 who declined, 106 (26.7%) agreed to serologic testing; 91 (85.8%) were seronegative. Among seronegative patients, 41 (45.1%) subsequently accepted vaccination. Integrating serologic testing increased overall vaccination uptake from 20.8% to 28.9%, an absolute increase of 8.2 percentage points and a relative increase of 39.4%. Approximately 2.6 serologic tests were required to generate 1 additional first-dose vaccination. Preliminary series-completion rates were 74.0% among those vaccinated at the initial offer and 87.8% among those vaccinated following serologic testing. Discussion: In this primary care setting, incorporating serologic testing into the workflow was associated with modestly improved hepatitis B vaccination uptake among vaccine-hesitant adults. Serologic results may help re-engage patients by providing personalized immunity information. Implementation considerations include staffing needs, laboratory access, patient portal engagement, and insurance coverage. Conclusion: The “Offer–Offer–Test–Vaccinate” strategy was associated with a modest increase in hepatitis B vaccine uptake among hesitant adults. This EMR-integrated, stepwise approach may offer a feasible and scalable strategy to reduce missed vaccination opportunities and support HBV prevention in adult primary care.

Abstract Introduction Periacetabular osteotomy (PAO) is performed in the setting of hip dysplasia to increase acetabular coverage of the femoral head and improve joint biomechanics and longevity. PAO fixation is generally achieved with two or three 4.5 mm screws, as compared to the generally more substantial plate and screw constructs used in the setting of acetabular fractures or pelvic ring injuries. The purpose of this study was to evaluate postoperative changes in hip joint center medialization and lateral acetabular coverage following PAO, understanding that these radiographic measures are generally used to guide intra-operative assessment of correction. Methods A retrospective chart review of 100 consecutive PAOs during 2021-2023 at a single academic institution by four surgeons was performed. Perioperative radiographs and fluoroscopy images were evaluated to measure lateral center edge angle (LCEA), Tönnis angle, and medialization of the hip joint center. The hip joint center was measured at one-third of the diameter of the femoral head from inferior to superior, to the ilioischial line, as previously validated by Fowler and colleagues. Results One hundred PAOs in 87 patients (87% female, mean age: 23.0 years) were included. Average preoperative radiographic parameters were 19.9° for LCEA, 12.5° for Tönnis angle, and 12.6 mm for distance from the femoral head to ilioischial line. Ninety-four cases (94%) used three screws, and 6 cases (6%) used two screws for unstable fragment fixation. On immediate postoperative films, average correction was to 28.3° for LCEA, 4.9° for Tönnis angle, and 1.9 mm of pre- to postoperative femoral head medialization (p≤0.001). Patients were radiographically followed for an average of 13.3 months, with an average time to radiographic union of 7.1 months. During the course of follow-up, LCEA increased to 29.3°, Tönnis angle remained to 5.0° (p=0.47), and medialization increased to 2.7 mm (p≤0.02), suggesting further significant but clinically modest increases in lateral coverage and femoral head medialization. Conclusion While the majority of lateral acetabular coverage and femoral head medialization occurs intra-operatively at the time of PAO, patients undergo modest but statistically significant postoperative increases in lateral coverage and medialization prior to radiographic union.

Abstract Purpose Acetabular overcoverage (pincer morphology) has been suggested to be both a source of pain and dysfunction as well as potentially protective against osteoarthritic change. The purpose of this study was to compare minimum 5-year clinical outcomes of patients undergoing primary hip arthroscopic labral repair with a lateral center edge angle (LCEA) of ≥ 40° as compared to non-dysplastic controls with an LCEA of 25-40°. Methods We identified all patients that underwent primary hip arthroscopy with labral repair between 2009-2019 at a single academic institution. Patients with LCEA ≥ 40° (pincer) were propensity matched to non-dysplastic controls with LCEA 25-40° on a 1:2 basis by sex, age, body mass index (BMI), and year of surgery. Patient-reported outcome measures (PROMs) including Visual Analog Scale (VAS) for pain, Tegner activity score, modified Harris Hip Score (mHHS), International Hip Outcome Tool (iHOT-12), and Hip Outcome Score (HOS) were analyzed, as were reoperations and conversions to total hip arthroplasty (THA). Results Fifty-five patients with pincer morphology (mean preoperative LCEA: 41.9°, Tonnis angle: -7.3°, alpha angle: 58.8°) were matched to 110 non-dysplastic controls (LCEA: 31.2°, Tonnis angle: 2.2°, alpha angle: 58.9°), resulting in a total of 165 hips in 163 patients (67% females, mean age: 37.7 years, BMI: 26.8 kg/m2). Pincer patients were corrected to a mean postoperative LCEA of 38.7° (p<0.0001), with 22 pincer patients having residual overcoverage, namely a postoperative LCEA ≥ 40° (range: 40.0-45.8°). At mean 7.8 years follow-up (range: 5.1-13.2), there was no difference in any postoperative PROMs between pincers and controls (p>0.15) and no difference in PROMs between patients with residual overcoverage and pincer patients with a postoperatively normalized LCEA (p>0.25). At final follow-up, 4 patients in the pincer cohort (7%) and 21 controls (19%) had converted to THA (p=0.046). Conclusion Patients with lateral acetabular overcoverage demonstrated similar and satisfactory postoperative PROMs at a minimum of 5-year follow-up compared to propensity-matched non-dysplastic controls, regardless of if the LCEA was corrected to <40°. Of note, non-dysplastic controls demonstrated an increased rate of conversion to THA, supporting the potentially chondroprotective role of acetabular overcoverage.

Abstract Purpose Patients presenting for iliopsoas tendinitis consultation after total hip arthroplasty (THA) often describe a prolonged time to diagnosis and subsequent surgical management. The purpose of this study was to quantify time from symptom onset to diagnosis and subsequent arthroscopic iliopsoas fractional lengthening, including number of providers seen. Methods Patients undergoing arthroscopic iliopsoas fractional lengthening after THA were prospectively identified between 2023-2025 at a single institution. Time from symptom onset to iliopsoas tendinitis diagnosis as well as arthroscopic lengthening were determined. Number of providers seen, diagnostic relief from preoperative iliopsoas bursal injections, and postoperative satisfaction after fractional lengthening were also evaluated to better quantify indications and outcomes of arthroscopic intervention in this population. Results A total of 44 hips in 41 patients (23 females and 18 males) were included (mean age: 64.7 ± 10.2, mean BMI: 29.9 ± 5.9 kg/m2). Of note, 7 patients (16%) had undergone revision THA prior to iliopsoas symptom onset. Patients had on average 2.2 ± 2.1 years of symptoms and saw 2.5 ± 1.7 [range: 1-8] providers prior to being diagnosed with iliopsoas tendinitis and referred for consideration of arthroscopic fractional lengthening. Preoperatively, 93% of patients underwent at least 1 iliopsoas bursal corticosteroid injection, with an average of 81.1% symptom relief during the diagnostic (anesthetic) phase. The mean time between THA and iliopsoas fractional lengthening was 4.8 ± 3.4 years, whereas the mean time between initial iliopsoas tendinitis symptoms to fractional lengthening was 3.1 ± 2.5 years. At a mean of 11.3 ± 6.8 months postoperatively, mean surgery satisfaction was 8.1 ± 2.6 on a scale of 1 to 10, with the vast majority of patients (89.5%) stating that they would undergo fractional lengthening again. Conclusion Patients often experience a protracted period of symptoms and see multiple clinicians prior to being diagnosed with iliopsoas tendinitis and undergoing arthroscopic management. In patients refractory to conservative management, arthroscopic fractional lengthening can provide high surgery satisfaction, with most patients stating they would undergo the procedure again. These findings highlight the importance of increased recognition and appropriate referral of patients with iliopsoas tendinitis following THA.

Abstract Purpose To investigate clinical outcomes, including patient reported outcome measures (PROMs), subjective anterior groin pain and hip flexion strength, and reoperation rates following arthroscopic iliopsoas fractional lengthening after total hip arthroplasty (THA). Methods Patients who were indicated for arthroscopic iliopsoas fractional lengthening after ipsilateral THA were prospectively identified between 2023-2025 at a single institution. Pre- and post-operative PROMs, including Visual Analog Scale (VAS), Tegner activity scale, Single Assessment Numeric Evaluation (SANE), and subjective anterior groin pain and hip flexion strength were analyzed. Reoperations at final follow-up were also evaluated. Results A total of 44 hips in 41 patients (23 females and 18 males) were included (mean age: 64.7 ± 10.2, mean BMI: 29.9 ± 5.9 kg/m2). Fifty-five percent of patients underwent surgery on their right hip. The mean postoperative follow-up timeframe was 10.0 ± 7.1 months. There was a significant improvement in postoperative PROMs compared to pre-operative levels for VAS at rest (1.3 ± 1.9 vs. 2.9 ± 2.2), VAS with use (3.1 ± 3.8 vs. 8.0 ± 1.6), Tegner activity scale (2.9 ± 1.3 vs. 2.1 ± 1.1), and SANE (74.0 ± 20.3 vs. 47.9 ± 23.4) (p<0.001 for all). Over 90% of patients reported feeling much better or slightly better regarding their anterior groin pain at 2-weeks post-operatively (93%), 6 weeks post-operatively (90%), 3 months post-operatively (93%), and at final follow-up (91%). Regarding hip flexion strength, 73% reported feeling much better or slightly better at 2-weeks post-operatively, 95% at 6-weeks post-operatively, 85% at 3 months post-operatively, and 61% at final follow-up. Only 2 patients (5%) reported feeling much weaker at final follow-up. Two of 44 hips (5%) underwent reoperation at final follow-up. One patient underwent a 2-stage revision THA at 5 months postoperatively due to infection, while 1 patient underwent an open iliopsoas release with acetabular screw removal and liner exchange. Overall, the mean surgery satisfaction was 8.1 ± 2.6 on a scale of 1-10. Conclusion Patients who underwent arthroscopic iliopsoas fractional lengthening following THA demonstrated satisfactory postoperative outcomes, with over 90% reporting durably improved anterior groin pain and nearly two-thirds reporting increased hip flexor strength throughout follow-up.