Citations

Background: Contemporary rotating-hinge total knee arthroplasties (RH-TKAs) have shown reasonable short-term survivorship in smaller series, but concerns remain regarding risks of aseptic and septic failure. The purpose of this study was to assess outcomes of contemporary RH-TKAs in one of the largest series to date. Methods: We retrospectively identified 575 RH-TKAs (60% used for aseptic etiologies and 40% used during reimplantation in 2-stage treatment of periprosthetic joint infection [PJI]) from 2002 to 2021 at a single institution. The mean age was 67 years, 58% were female, and the mean body mass index was 33 kg/m 2 . Sixty-five percent had Anderson Orthopaedic Research Institute (AORI) type-2B or 3 bone loss. Kaplan-Meier survivorship analyses were performed. The mean follow-up was 6 years (range, 2 to 19 years). Results: Survivorship free from any revision was 76% at 5 years and 64% at 10 years. The most common revision indications were PJI (54%) and aseptic loosening (20%). RH-TKA used in the primary setting showed better survivorship compared with RH-TKA used during reimplantation after PJI (79% versus 60% at 10 years). Survivorship free from revision for aseptic loosening was 96% at 5 years and 90% at 10 years. Survivorship free from revision for PJI was 84% at 5 years and 81% at 10 years. Survivorship free from revision for PJI was even lower for RH-TKAs used during reimplantation, 74% at 5 years and 73% at 10 years. RH-TKA used during reimplantation in the treatment of PJI was associated with an increased risk of any revision (HR = 2, p < 0.001). Radiographic analysis of 425 knees that were not revised and had radiographs available for review showed that 6% of femoral components and 8% of tibial components had evidence of loosening at the time of final follow-up. The mean Knee Society Score improved from 33 to 69 at 2 years (p < 0.001). Conclusions: The 10-year survivorship free from aseptic loosening was 90% in this large series of RH-TKAs. This represents one of the best survivorships free from aseptic loosening published to date. Knees with prior PJI had markedly poorer survivorship than knees treated for aseptic etiologies, with double the risk of revision. Level of Evidence: Therapeutic Level III . See Instructions for Authors for a complete description of levels of evidence.

INTRODUCTION: Chronic gastrointestinal (GI) conditions, including irritable bowel syndrome and other disorders of gut-brain interaction, are prevalent and costly, and fragmented care contributes to suboptimal outcomes. Virtual and multidisciplinary care models may improve outcomes. Objectives: We aimed to (i) characterize patients receiving virtual GI care, (ii) report patient engagement with and patient-reported outcomes after virtual multidisciplinary care, and (iii) report healthcare utilization and costs from a payer perspective among patients vs propensity score-matched controls identified from claims data. METHODS: We collected descriptive data on patient demographics, clinic provider visits, symptoms, and patient-reported outcomes from 3/2021 to 9/2022. To evaluate healthcare utilization and costs, we conducted difference-in-difference analyses using claims data compared with a propensity score-matched control group. RESULTS: Among 234 patients (71% women, mean age 45.4 ± 13.2 years), 51% received a new GI diagnosis, predominately disorders of gut-brain interaction (63%). Engagement criteria were met by 80% (n = 187), who completed a mean of 10 visits and median time-to-first appointment of 6 days. Dietitians (93%), psychologists (76%), and health coaches (64%) were frequently used. Engaged patients exhibited significant improvements from preclinic to postclinic in irritable bowel syndrome severity (226.7–145.6), symptom control (20.2%–86.6%), quality-of-life dysphoria (27.5–32.8), missed workdays (1.0–0.7), and satisfaction (37.4%–96.3%) (all P < 0.05). Compared with matched controls, a significantly smaller percent of patients had imaging (15% vs 44%; P < 0.0001) and GI-related emergency department visits (4% vs 10%; P = 0.0028), which contributed to reductions in GI-related costs ($443 per member per month; P = 0.047) and all-cause costs ($676 per member per month; P = 0.043), equating to annualized savings of $5,316 and $8,112, respectively. DISCUSSION: Virtual multidisciplinary GI care was associated with high engagement, improved clinical outcomes, and reduced healthcare utilization and costs.

Abstract Neuromodulatory subcortical systems (NSSs) are uniquely susceptible to dementia‐related pathology, leading to frequent molecular and behavioral impairments associated with altered function of these nuclei. Some of these systems display clear sex‐specific cytoarchitecture and signaling leading to distinct physiology and behavioral outputs in males and females, while other regions display nominal sex differences. However, the relevance of sex differences in modulating dysfunction of NSSs in Alzheimer's disease (AD) and related dementias is not well understood. This review is a joint effort by the Neuromodulatory Subcortical Systems and Sex and Gender Differences in Alzheimer's Disease Professional Interest Areas of the Alzheimer's Association. We review sex differences in NSSs, both in non‐disease states and in AD models and patients. We highlight the possible role of NSSs in driving sex‐specific AD susceptibility and potential footholds for sex‐based interventions targeting these systems. We conclude by outlining immediate and long‐term actions to address the intersection of NSSs, sex, and AD.

Abstract Diffuse leptomeningeal glioneuronal tumors (DLGNT) are rare central nervous system tumors. Our understanding of the clinical course, prognostic factors, and optimal treatment strategies remains limited. Histologic, molecular, and clinical data were collected and analyzed for 25 patients with DLGNT reviewed at St. Jude Children’s Research Hospital. The median age at diagnosis was 6 years (11 months-20 years). Nineteen (72%) patients were male. The disease was localized at diagnosis in 12 (48.0%) patients, with most tumors localized in the spinal cord. BRAF fusion was present in 22 (95.6%) of 23 patients who had material for testing. Of 18 patients who had tissue for DNA methylation profiling, 3 (16.7%) matched to DLGNT MC-1, 3 (16.7%) to DLGNT MC-2, and 12 (66.7%) did not match to a DLGNT subclass. Median follow-up was 63 months. Twenty-four (96.0%) patients received adjuvant therapy after initial diagnosis or at progression. Thirty-five cytotoxic chemotherapy and 24 single-agent targeted therapy regimens were used in 22 and 13 patients, respectively. With targeted therapy, 3 (12%) patients had partial responses. Eleven (44.0%) received radiotherapy. Median progression-free survival (PFS) after a patient’s first chemotherapy, targeted therapy, or radiotherapy regimen was 44 months (1-77), 11 months (4-39), and 16.5 months (9-23), respectively. The 5-year PFS was 18.7%±9.2, while the 5-year overall survival (OS) was 82.4%±9.2. The 5-year OS was lower in patients older than 9 years at diagnosis (60.0%±21.9 vs 91.7%±8.0, p = 0.02). Ki67 &gt;4% was associated with worse PFS (0%±0 vs 24.6%±11.9 at 5 years, p = 0.03). Initial disease dissemination (localized vs. disseminated) and 1q gain status do not influence PFS or OS. PFS for DLGNT remains poor across all treatment modalities, including targeted therapies, despite the high frequency of BRAF fusions. Due to its rarity, establishing optimal therapeutic strategies for DLGNT requires additional treatment and outcome data and prospective multi-institutional trials.

Abstract High-grade gliomas (HGGs) are aggressive tumors with poor outcomes and limited treatment options. Here, we combined genomic and transcriptomic tumor profiling with drug testing in a patient-derived 3-dimensional culture model to identify individualized treatments and predictive biomarkers. Activity of single agents targeting frequently dysregulated glioma pathways was relatively poor ex vivo and generally reflected historical patient data. However, compounds targeting PI3K, epigenetic, and survival/senescence signaling were effective in some cases. Drug sensitivity correlated with transcriptional rather than genomic features and suggested heterogeneity as a resistance mechanism. Bromodomain and extraterminal domain inhibition was particularly effective in tumors enriched in the mesenchymal transcriptional subtype, promoted proneural transition, and was overcome by upregulated PI3K signaling. Notably, combinations were largely effective, with 6 strategies exhibiting stronger efficacy than corresponding single agents in most cases (58-77%). This study identifies HGG vulnerabilities and associated biomarkers, resistance mechanisms, and effective combination strategies that warrant further clinical validation. Graphical Abstract

Background: Cardiac CT acquired during the acute stroke imaging protocol is an emerging diagnostic modality to detect cardiac thrombi. We aimed to determine its diagnostic yield in a large, international, multicenter study. Methods: We performed an individual patient data meta-analysis by pooling prospective and retrospective observational data of patients with acute ischemic stroke (AIS) who underwent cardiac CT (ECG-gated or non-ECG-gated) as part of the acute imaging protocol between May 2018 and June 2024. We excluded patients with a TIA or stroke mimic. The primary outcome was the proportion of patients with a cardiac thrombus detected on cardiac CT. Secondary outcomes were additional scan time and radiation dose, comparison of yield with echocardiography, and 90-day mortality and recurrent ischemic stroke rates. Results: We included 3940 patients from 4 hospitals (median age 74 [IQR 63-82], 58.0% male, median NIHSS 6 [IQR 3-12], median time onset to hospital arrival 100 minutes [IQR 62-185]). Atrial fibrillation at baseline was present in 23.1% patients, and 29.6% had a large vessel occlusion. Cardiac CT was non-diagnostic in 17 (0.4%) patients. In total, cardiac CT detected 254 cardiac thrombi in 243/3923 (6.2%) patients. Thrombi were located in the left atrial appendage (n=193), left atrium (n=19), and left ventricle (n=42). Of 95/243 (39.1%) patients with a cardiac thrombus that underwent echocardiography (median interval cardiac CT-echocardiography: 2 days), transthoracic echocardiography detected a thrombus in 18/92 (19.6%) patients and transesophageal echocardiography in 2/5 (40.0%) patients. The diagnostic yield in patients that underwent both modalities was higher for cardiac CT (OR 7.5 [CI 4.0-15.3], p<0.001). Median additional scan time was 6 minutes (IQR 5-7) for ECG-gated and 17 seconds (IQR 15-63) for non-ECG-gated cardiac CT. Median additional radiation dose was 5.4mSv (IQR 3.0-7.6). Patients with a cardiac thrombus on cardiac CT had higher 90-day mortality than those without a thrombus (33.3% vs 14.6%, p<0.001). We found no difference in 90-day recurrent stroke rate (5.4% vs 4.4%, p=0.50). Conclusion: Routine cardiac CT performed during the acute stroke imaging protocol detects a cardiac thrombus in 1 out of 16 patients with AIS, with a 7-times higher yield than routine echocardiography. Mortality rate was doubled in patients with a cardiac thrombus, but 90-day stroke recurrence risk did not differ.

Background: The rate of intracardiac thrombus detection in the hyperacute phase of stroke varies from 5% to 12% between studies. Our aim was to compare the thrombus detection rate between ECG-gated and non-ECG-gated cardiac CT protocols in acute stroke patients, using data from a large, international, multicentre registry. Methods: We conducted an individual patient data meta-analysis by pooling prospective and retrospective observational data from stroke patients assessed at four comprehensive stroke centres who underwent either ECG-gated or non-ECG-gated cardiac CT (extended CT angiography or two-phase non-ECG-gated cardiac CT) as part of the acute stroke imaging protocol between May 2018 and June 2024. The primary outcome was the proportion of patients with a cardiac thrombus in gated vs non gated techniques. Results: Of 3,940 patients, 1,474 (37.4%) underwent ECG-gated and 2,466 (62.6%) non-ECG-gated cardiac CT. Patients in the ECG-gated group were younger (median age 72 [IQR 62–81] vs. 74 [IQR 64–82] years, p = 0.000) and had a lower NIHSS at baseline (median 5 [IQR 2–12] vs. 6 [IQR 3–13], p < 0.00). There was a higher rate of thrombus detection with ECG-gated CT compared to non-gated CT (7.5% vs. 5.5%, p = 0.011. The association remained significant after adjusting for age, sex, baseline NIHSS score, and baseline atrial fibrillation (adjusted OR 1.87, 95% CI 1.42–2.47, p = 0.000). ECG-gated CT was associated with lower radiation dose (3.6 vs. 6.3 mSv, p = 0.000) but longer acquisition time (5.8 vs. 0.28 min, p = 0.000). Conclusion: ECG-gated cardiac CT has a higher detection rate for intracardiac thrombus detection compared to non-ECG-gated CT in patients with acute ischemic stroke.

Background/Objective: The COVID-19 pandemic led to a widespread transition to online learning. Yet, it is unclear how this shift in learning format impacted school attendance in adolescents with chronic pain, a group that struggles with school absenteeism. This study compared school attendance and format (e.g., in-person, online) in patients with chronic pain attending an Intensive Interdisciplinary Pain Treatment Program (IIPT) before the pandemic to an age- and gender-matched sample of youth attending the program after the pandemic. Methods: Participants were 226 school aged adolescents (13–18 years; M age = 15.89, SD = 1.46) enrolled in an IIPT before and after the COVID-19 pandemic. Patients admitted before March 2020 (pre-pandemic group; n = 113) were compared to an age- and gender-matched group of patients who were admitted to the IIPT from November 2021 to November 2023 (post-pandemic group = 113). Upon admission to the program, participants completed validated measures of internalizing symptoms and functional disability. They also completed structured questions related to pain and school history. Results: Significantly more patients in the post-pandemic group were attending school through online and home-schooling options (p < 0.01). Youth who attended the IIPT after the pandemic missed fewer school days (p < 0.05) than those who attended before the pandemic. The groups did not differ in functional disability or internalizing symptoms. However, participants in the post-pandemic group who attended online school missed more school days (p < 0.01) and experienced greater functional disability (p < 0.05) than those who attended in person. Conclusions: The findings highlight how the COVID-19 pandemic may lead to sustained changes in the way adolescents with chronic pain attend school, with implications for increased functional disability and school dropout among this vulnerable population.

Abstract BACKGROUND Children exposed to poverty during frontline therapy for B-lymphoblastic leukemia (B-ALL) experience inferior overall survival (OS), higher relapse rates, and earlier relapse than their peers. Real-world data describing treatment patterns and survival after relapse of B-ALL are lacking and, as a result, the impact of poverty following relapse remains poorly understood. This study evaluated the association of poverty exposure, proxied by insurance status, with post-relapse survival and explored potential explanatory mechanisms, including disease biology and therapy utilization. METHODS Data from Retrospective Study of Contemporary Approaches to First Relapse in B-ALL (ReCALL-1), a multicenter retrospective cohort study of patients &lt; 30 years old with first relapse of B-ALL from 2018-2022, were used. The primary exposure was poverty, proxied by insurance status at relapse, categorized as any private insurance (poverty unexposed), public-only insurance (poverty exposed), no insurance, or unknown; the latter two were not included in comparative analyses due to low numbers. The primary outcome was OS. Secondary outcomes included measurable residual disease (MRD)-negative second complete remission (CR2), relapse after CR2, non-relapse mortality (NRM), with relapse treated as a competing risk, and receipt of cellular and immunotherapies. RESULTS Among 462 patients from 31 U.S. institutions, 41% had private insurance, 47% public-only insurance, 2% no insurance, and 10% unknown. Compared to privately insured patients, those with public insurance were more likely to be Hispanic (56% vs 19%, p&lt;0.001) and have non-English preferred language (30% vs 6%, p&lt;0.001). Non-Hispanic Black patients comprised 9% of those with public insurance and 5% of those with private insurance. Disease characteristics that differed by insurance status at relapse included: Ph-like cytogenetics, more common in publicly insured (23% vs 11%, p=0.002), and infant ALL, more common in privately insured patients (10% vs 5%, p=0.06). Publicly insured patients were more likely to have experienced major organ toxicity during frontline therapy (32% vs 18%, p=0.002) and very early relapse (&lt;18m from diagnosis: 43% vs 32%, p=0.07). Other demographic and disease characteristics, including relapse site and cytomolecular features, were similar by insurance status. With a median follow-up of 51 months from relapse, 4-year OS differed by insurance (log-rank p=0.02): 72% for private vs 56% for public insurance. After adjusting for race/ethnicity and language, public insurance increased the hazard of death by 65% (aHR 1.65 95% CI 1.13-2.42, p=0.004). The association remained, but was attenuated, when unbalanced disease characteristics (time to relapse, infant ALL, Ph-like cytogenetics, prior organ dysfunction) were included (aHR 1.47, 95% CI 1.00-2.16, p=0.05). Rates of MRD-negative CR2 were similar (85% public vs 87% private). However, point estimates suggested publicly insured patients had more relapse after CR2 (44% vs 37%, p=0.42) and higher 4-year NRM (16% vs 10%, Gray's test p=0.12), though neither were significant. Treatment choices for first relapse did not differ by insurance status. Utilization of intensive reinduction (91% vs 95% for public vs private, p=0.18) and clinical trial enrollment (22% for both) were similar. Receipt of cellular therapies did not significantly differ by public vs private insurance: Chimeric Antigen Receptor-T cells (CAR-T: 38% vs 34%, p=0.41), hematopoietic cell transplant (HCT: 42% vs 47%, p=0.32). Use of blinatumomab trended higher in those with private insurance (36% vs 45%, p=0.07), and inotuzumab was similar (11% for both, p=0.87). Median time from relapse to CAR-T or HCT was comparable (to CAR-T 102 vs 100 days, to HCT 117 vs 114 days). CONCLUSION This is the first study to demonstrate differential survival by insurance type, a proxy for poverty exposure, after first relapse of B-ALL. In this large multicenter, real-world cohort, patients with public insurance had worse OS after relapse than those with private insurance. The survival disparity existed independent of other SDOH factors. Adjustment for known high-risk disease features only partially accounted for the observed differences in OS. In contrast, rates of MRD-negative CR2 and receipt of CAR-T and HCT were comparable across insurance types. These findings highlight the urgent need to identify effective interventions that will ensure equitable outcomes after relapse.