University of Missouri–Kansas City

The etiology of early-onset scoliosis (EOS) has been shown to significantly influence baseline parent-reported health-related quality of life (HrQOL). In combining these etiology groups, we obligatorily lump together many disparate diagnoses, particularly true in the neuromuscular (NM) cohort. We sought to evaluate the influence of underlying neuromuscular diagnosis on the HrQOL at 5 years following surgery for EOS. A retrospective review of a multi-center EOS database was performed. Children treated with primary distraction-based, growth-friendly instrumentation (GFI) for EOS with complete baseline, 2-year, and 5-year post-surgical EOSQs were included. Neuromuscular scoliosis patients, as classified by the C-EOS system, were isolated and subdivided by underlying diagnosis into 5 groups. EOSQ domains and composite HrQOL score at presentation, 2-year, and 5-year follow-up were compared across underlying diagnosis. A total of 65 neuromuscular EOS patients were identified (mean 7.6 ± 1.99 years of age, 50% female). Cerebral palsy was the most common underlying diagnosis (30%, N = 18), followed by spinal muscular atrophy (SMA, N = 16). There were differences in EOSQ domains with CP, SMA, and MD having significantly lower scores than Chiari/Syrinx patients at 2-year follow-up. Chiari/Syrinx patients demonstrated EOSQ scores statistically similar to idiopathic EOS patients at all time points (P > 0.05). CP patients were most likely to experience improvement in HrQOL at 5-year follow-up. Underlying NM diagnosis has direct implications on treatment response following GFI for EOS. Cerebral palsy patients demonstrate the best improvement in HrQOL at 5 years following surgery while others actually deteriorate over time. Children with EOS related to Chiari and Syringomyelia had similar HrQOL scores to idiopathic EOS and may not be best suited for inclusion in NM cohorts when assessing HrQOL scores following treatment. Increasing population-based HrQOL data may allow further refinement and prognostication of neuromuscular diagnoses over time.

Importance Multisystem inflammatory syndrome in children (MIS-C) is a life-threatening complication of COVID-19 infection. Data on midterm outcomes are limited. Objective To characterize the frequency and time course of cardiac dysfunction (left ventricular ejection fraction [LVEF] <55%), coronary artery aneurysms ( z score ≥2.5), and noncardiac involvement through 6 months after MIS-C. Design, Setting, and Participants This cohort study enrolled participants between March 2020 and January 2022 with a follow-up period of 2 years. Participants were recruited from 32 North American pediatric hospitals, and all participants met the 2020 Centers for Disease Control and Prevention case definition of MIS-C. Exposure MIS-C after COVID-19 infection. Main Outcomes and Measures Outcomes included echocardiography core laboratory (ECL) assessments of LVEF and maximum coronary artery z scores (zMax); data collection on cardiac and noncardiac sequelae during hospitalization and at 2 weeks, 6 weeks, and 6 months after discharge; and age-appropriate Patient-Reported Outcomes Measurement Information Systems (PROMIS) Global Health Instruments at follow-up. Descriptive statistics, linear regression models, and Kaplan-Meier analysis were used. Results Of 1204 participants (median [IQR] age, 9.1 [5.6-12.7] years; 724 male [60.1%]), 325 self-identified with non-Hispanic Black race (27.0%) and 324 with Hispanic ethnicity (26.9%). A total of 548 of 1195 participants (45.9%) required vasoactive support, 17 of 1195 (1.4%) required extracorporeal membrane oxygenation, and 3 (0.3%) died during hospitalization. Of participants with echocardiograms reviewed by the ECL (n = 349 due to budget constraints), 131 of 322 (42.3%) had LVEF less than 55% during hospitalization; of those with follow-up, all but 1 normalized by 6 months. Black race (vs other/unknown race), higher C-reactive protein level, and abnormal troponin level were associated with lowest LVEF (estimate [SE], −3.09 [0.98]; R ² = 0.14; P =.002). Fifteen participants had coronary artery z scores of 2.5 or greater at any time point; 1 participant had a large/giant aneurysm. Of the 13 participants with z scores of 2.5 or greater during hospitalization, 12 (92.3%) had normalized by 6 months. Return to greater than 90% of pre–MIS-C health status (energy, sleep, appetite, cognition, and mood) was reported by 711 of 824 participants (86.3%) at 2 weeks, increasing to 548 of 576 (95.1%) at 6 months. Fatigue was the most common symptom reported at 2 weeks (141 of 889 [15.9%]), falling to 3.4% (22 of 638) by 6 months. PROMIS Global Health parent/guardian proxy median T scores for fatigue, global health, and pain interference improved significantly from 2 weeks to 6 months (fatigue, 56.1 vs 48.9; global health, 48.8 vs 51.3; pain interference, 53.0 vs 43.3; P < .001) and by the 6-week visit were at least equivalent to prepandemic population norms. Conclusions and Relevance Results of this cohort study suggest that although children and young adults with MIS-C can have severe disease during the acute phase, most recovered quickly and had a reassuring midterm prognosis.

Administrative databases are powerful tools for pediatric research but lack patient‐level microbiology results. This study aimed to determine the accuracy of pathogen discharge diagnosis codes for children hospitalized with acute hematogenous musculoskeletal infections (MSKIs). Medical records for 244 children hospitalized with acute hematogenous MSKIs were manually reviewed to determine which bacterial pathogen, if any, was identified for each MSKI based on microbiology results obtained during the hospitalization. Microbiology results for each patient were then compared to their discharge diagnoses in the Pediatric Health Information System (PHIS) database to determine the accuracy of pathogen discharge codes. Discharge diagnostic codes correctly matched the microbiology results in 89.3% of encounters. Sensitivity and specificity for Staphylococcus aureus discharge diagnostic codes were 88.6% and 96.4% respectively for methicillin‐susceptible S. aureus and 92.9% and 99.5% for methicillin‐resistant S. aureus . Pathogen discharge codes are reliable surrogates that accurately reflect the microbiology results for children with MSKIs.

Objective To review the efficacy of iloperidone for mania associated with bipolar I disorder and discuss its safety profile (eg, QTc prolongation, orthostatic hypotension, and metabolic adverse effects). Data sources Literature was identified using PubMed (1966-September 2024), OVID (1984-November 2024), and clinicaltrials.gov. Search terms included iloperidone, bipolar disorder, and mania. Study selection and data extraction The study included trials evaluating iloperidone for treating bipolar mania. Data synthesis In one phase 3 study, iloperidone demonstrated significant improvement in mania symptoms at day 28 on all primary (ie, Young Mania Rating Scale) and secondary outcomes (Clinical Global Impression-Severity/Change scales) compared to placebo. Iloperidone was well tolerated, with tachycardia, dizziness, dry mouth, alanine aminotransferase elevation, nasal congestion, increased weight, and somnolence reported as common adverse effects. Relevance to patient care and clinical practice in comparison to existing drugs Since there are no head-to-head studies comparing iloperidone with other second-generation antipsychotics for bipolar mania, other treatment considerations drive medication selection. Iloperidone is unavailable in a generic formulation; thus, its use will be associated with higher costs. It is dosed twice daily, which may negatively impact adherence. Iloperidone is associated with a moderate risk of QTc prolongation, metabolic adverse effects, and orthostatic hypotension, which will limit its use in certain patient populations. QTc prolongation is dose related, so drug interactions involving CYP2D6 and CYP3A4 inhibition can have serious consequences. Conclusion In the pivotal trial, iloperidone was effective in treating adults with an acute manic or mixed episode associated with bipolar I disorder and was safe and well tolerated.

OBJECTIVES The 22-modifier in the Current Procedural Terminology (CPT) system indicates increased surgical procedure complexity, aiming to secure greater reimbursement for surgeons. This study investigated the 22-modifier on reimbursement amounts after acetabular fracture fixation. METHODS Design : Retrospective cohort study. Setting Academic Level I Trauma Center. Patient Selection Criteria Included were patients with third party reimbursement for acute acetabular fracture (AO/OTA 62A-C) fixation through an open approach from 2005 to 2021 as identified using CPT codes 27226, 27227 and 27228. Outcome Measures and Comparisons Chart review identified procedures where the 22-modifier for obesity or fracture complexity was applied. A cohort without the 22-modifier matched by diagnosis, primary CPT code and insurance carrier was made for comparison. The primary outcome measure was the difference in financial reimbursement when the 22-modifier was used. Secondary outcomes were the difference in billed charges and operative time. RESULTS A total of 785 cases were initially identified with 747 meeting the inclusion criteria, and 73 having the 22-modifier applied. After removing surgeries that did not receive compensation from their insurance, 52 of these patients were compared to 52 matched cases without a 22-modifier. The 22-modifier group and the non-modifier group had no significant difference in reimbursed amounts ($4,112.71 USD vs.$3,851.00, p = 0.644). However, patients in the 22-modifier group had significantly greater billed charges ($8,007.35 vs.$7,120.94 USD; p = 0.0096), longer operative times (301.7 vs. 240.2 minutes, p < 0.001) and greater body mass index (BMI) (43.1 vs 29.3 kg/m2; p < 0.001). CONCLUSIONS Despite increased complexity and greater billed charges, the use of a 22-modifier in acetabular fracture cases did not result in improved collected reimbursements, and reimbursement is equal to when the 22-modifier is not used. Policymakers and insurers should revise reimbursement structures to better align reimbursements for acetabular fixation with surgical complexity. LEVEL OF EVIDENCE Level III

Knee osteoarthritis significantly impacts mobility and quality of life. This condition is a leading cause of disability in aging populations, with total knee replacement commonly sought in advanced cases. Traditional nonoperative management strategies, including anti-inflammatories, corticosteroid injections, and hyaluronic acid, often provide limited relief, especially in severe cases. Recently, regenerative therapies such as amniotic suspension allografts (ASA) have emerged as promising alternatives due to their anti-inflammatory and regenerative properties, which may counteract the catabolic effects of osteoarthritis. This systematic review evaluated the efficacy and safety of ASA in reducing pain and improving function among knee osteoarthritis patients. Following the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines, a comprehensive search of PubMed and Embase databases initially identified 1,733 studies pertaining to ASA, of which 1,575 were screened, and 9 studies ultimately met the inclusion criteria for detailed analysis of ASA in the treatment of knee osteoarthritis. Data extraction and narrative synthesis focused on outcomes such as pain reduction and functional improvement using the Knee Injury and Osteoarthritis Outcome Score (KOOS) and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), as well as safety profiles. The results demonstrated notable improvements in pain scores following ASA treatment, as shown by studies reporting increases in KOOS pain scores over 6 months, which generally outperformed hyaluronic acid and saline treatments in pain reduction. Similarly, ASA treatment was associated with substantial improvements in physical function outcome scores, enhancing patients' ability to perform daily activities. Patient-reported outcomes also indicated higher quality of life and functional status, with most patients experiencing high levels of satisfaction. Additionally, ASA's safety profile was favorable, with adverse events primarily mild to moderate in nature, including a few transient events such as knee stiffness and myalgias. This systematic review highlights ASA as an effective therapeutic option for knee osteoarthritis, although further studies focusing on long-term radiographic outcomes and mechanisms of action are recommended to fully establish its benefits and optimize treatment protocols.

Background Retrotransposon‐derived extrachromosomal circular DNA (eccDNA) was extracted and sequenced from brains with Alzheimer’s disease, progressive supranuclear palsy, or healthy controls. Retrotransposon‐derived DNA was visualized outside of the nucleus in these phenotypes with phospho‐STING. Drosophila were used as a model to study extranuclear retrotransposon DNA. Method DNA was extracted from post‐mortem human patients with AD (n = 6), PSP (FTD) (n = 6), or no pathology (n = 6). The DNA was treated with exonucleases to degrade linear DNA and the circular DNA was isolated. Post‐mortem cryosections of AD, PSP, or healthy control brains were used for fluorescent in‐situ hybridization (FISH) of retrotransposon sequences. Co‐immunofluorescence of phospho‐STING was performed on FISH tissue. Drosophila brains were also used for FISH of retrotransposons. Digital qPCR was used to measure copy number of retrotransposons in human and fly tissue. Result Preliminary data suggests an increase in phospho‐STING in AD and PSP brains compared to controls. Preliminary data also suggests an enrichment of retrotransposon DNA in circular DNA sequencing in tau pathology compared to controls. Conclusion Retrotransposon‐derived eccDNA may be an activator of the cGAS‐STING pathway in AD and PSP.

Segmental duplications (SDs) contribute significantly to human disease, evolution and diversity but have been difficult to resolve at the sequence level. We present a population genetics survey of SDs by analyzing 170 human genome assemblies (from 85 samples representing 38 Africans and 47 non-Africans) in which the majority of autosomal SDs are fully resolved using long-read sequence assembly. Excluding the acrocentric short arms and sex chromosomes, we identify 173.2 Mb of duplicated sequence (47.4 Mb not present in the telomere-to-telomere reference) distinguishing fixed from structurally polymorphic events. We find that intrachromosomal SDs are among the most variable, with rare events mapping near their progenitor sequences. African genomes harbor significantly more intrachromosomal SDs and are more likely to have recently duplicated gene families with higher copy numbers than non-African samples. Comparison to a resource of 563 million full-length isoform sequencing reads identifies 201 novel, potentially protein-coding genes corresponding to these copy number polymorphic SDs.

Introduction Hospitalisation represents an opportunity to identify and treat e-cigarette use among adolescents and young adults (AYAs). Knowledge on how to provide this care is lacking. We aim to fill this gap by developing an e-cigarette use intervention and evaluating preliminary efficacy and implementation outcomes among hospitalised AYAs. Methods and analysis We will enrol 144 hospitalised AYAs (14–21 years) who report past 30-day e-cigarette use and randomise 2:1 to intervention or control arms. We will develop an evidence-based intervention that includes education, motivational interviewing, quit planning and nicotine replacement therapy prescription offered confidentially in person during the hospital stay and 4 weekly phone booster sessions. Control participants will receive brief advice and quit programme resources. We will assess self-reported demographics, e-cigarette use behaviours, nicotine dependence, motivation and confidence to quit at baseline and postintervention. Our primary outcome is self-reported 30-day point prevalence e-cigarette abstinence at the 3-month follow-up with biochemical salivary cotinine confirmation. Our secondary implementation outcomes are feasibility, acceptability and fidelity. We will assess our primary outcome using a generalised linear model assuming an underlying binomial distribution and logit link function. X ² (categorical variables) and Wilcoxon rank-sum (continuous variables) tests will be used to assess differences between groups. Ethics and dissemination Careful consideration will be given to ethical recruitment and implementation of all elements of the study. Our study protocol and documents will be reviewed and approved by the institutional review board at the affiliated academic institution. Only approved study team members will access participant data, and all data will be managed in accordance with institutional review board and Health Insurance Portability and Accountability Act (HIPAA) requirements. Study results will be disseminated to our public committee, youth research advisory board, to relevant stakeholders and through publication. Trial registration number NCT05936099 ; registered on 30 June 2023. Study recruitment and enrolment began in August 2023 and is ongoing.

Background Frailty has been associated with inferior outcomes in patients with primary pulmonary hypertension (PPH). There is a lack of national data to assess if hospital frailty risk score (HFRS) is associated with worse inpatient outcomes in PPH. Methods Our retrospective study used the Nationwide Readmission Database (NRD). First, we extracted all cases older than 18 years who were discharged with a principal diagnosis of PPH between January and November 2016 to 2019 to allow for a 30-day follow-up. Appropriate survey and domain analyses were applied to obtain national estimates using SAS 9.4. Results We identified 4,555 cases. HFRS <5 was present in 56% (n = 2,555) of the cohort. Patients with an intermediate-to-high frailty risk score (HFRS ≥5) were older than those with a low frailty risk score (HFRS <5), with a mean age of 61 versus 54 years (p < 0.01), and had slightly fewer women (75 vs. 78%, p = 0.09). Patients with HFRS >5 had a higher prevalence of dementia, depression, diabetes mellitus, malignancy, acute encephalopathy, coagulopathy, heart failure, and chronic (liver and renal) diseases (p < 0.01). Also, they had higher inpatient mortality during index admission (14 vs. 2%, p < 0.001), and all-cause 30-day readmission rates (38 vs. 33%, p = 0.01). Univariate analysis suggests a positive correlation between the degree of frailty and the odds of inpatient mortality (referenced to HFRS <5). The HFRS 5 to 10 group has an odds ratio (OR) of 5 (95% confidence interval [CI]: 3.3–8), the HFRS 10 to 15 group has an OR of 14 (95% CI: 8–23), and the HFRS >15 group has an OR of 20 (95% CI: 9–45). Even after adjusting for age, gender, and significant comorbidities, the single most important factor associated with higher odds of inpatient mortality was HFRS >5 (OR: 5.5 [95% CI: 3.7–8.3], p < 0.001) followed by acute myocardial infarction, acute encephalopathy, heart failure, chronic liver disease, and malnutrition. Length of stay had linear trend with HFRS (mean of 6 days for HFRS <5 vs. 11 days for HFRS 5–10 vs. 19 days for HFRS >10, p < 0.001). Conclusion Adverse inpatient outcomes correlate with the severity of HFRS in PPH.

Developing efficient path integral (PI) methods for atomistic simulations of vibrational spectra in heterogeneous condensed phases and interfaces has long been a challenging task. Here, we present the h-CMD method, short for hybrid centroid molecular dynamics, which combines the recently introduced fast quasi-CMD (f-QCMD) method with fast CMD (f-CMD). In this scheme, molecules that are believed to suffer more seriously from the curvature problem of CMD, e.g., water, are treated with f-QCMD, while the rest, e.g., solid surfaces, are treated with f-CMD. To test the accuracy of the newly introduced scheme, the infrared spectra of the interfacial D2O confined in the archetypal ZIF-90 framework are simulated using h-CMD compared to a variety of other PI methods, including thermostatted ring-polymer molecular dynamics (T-RPMD) and partially adiabatic CMD as well as f-CMD and experiment as reference. Comparisons are also made with classical MD, where nuclear quantum effects are neglected entirely. Our detailed comparisons at different temperatures of 250–600 K show that h-CMD produces O–D stretches that are in close agreement with the experiment, correcting the known curvature problem and redshifting of the stretch peaks of CMD. h-CMD also corrects the known issues associated with too artificially dampened and broadened spectra of T-RPMD, which leads to missing the characteristic doublet feature of the interfacial confined water, rendering it unsuitable for these systems. The new h-CMD method broadens the applicability of f-QCMD to heterogeneous condensed phases and interfaces, where defining curvilinear coordinates for the entire system is not feasible.

The anterolateral ligament (ALL) is considered a secondary stabilizer of internal rotation and, due to proximity to the lateral collateral ligament (LCL), it may contribute to anterolateral rotatory stability. This study characterized the anatomy of the ALL and associated tissues of the anterolateral complex (ALC) to determine if structural and histological compensatory adaptations exist in patients without an ALL. Forty-nine cadaveric knees were dissected from distal-to-proximal using established landmarks with the aid of internal rotation stress to localize the ALL (if present), LCL, iliotibial band (ITB), and anterolateral capsule. The width and thickness of ALL and LCL were measured with digital calipers at the origin, middle, and insertion, and cross-sectional areas were calculated. ALL and LCL length and ITB thickness were also obtained. Samples of each tissue were stained with hematoxylin and eosin and picrosirius red, and histological images were evaluated with ImageJ to quantify collagen density (mean gray value [mgv]) and quantity (percent coverage). Size measurements and collagen characteristics were compared between ALL-present and ALL-deficient knees. The ALL was identified in 63% of knees with mean cross-sectional areas of 8.9, 5.8, and 9.7 mm2 at the origin, middle, and insertion, respectively. Mean collagen density of the ALL was 106.9 mgv on a scale of 0 (black) to 255 (white), and overall collagen quantity was 40.3%. Proximal LCL width (p = 0.04), distal LCL thickness (p = 0.03), and cross-sectional area (p = 0.01), and ITB thickness (p = 0.02) were significantly greater in ALL-deficient knees. A significantly higher collagen density was found within the LCL (p = 0.04), and higher overall quantity of collagen within the LCL (p < 0.01) and ITB (p < 0.01), of ALL-deficient knees. Gross anatomical and histological alterations exist in knees without an ALL compared with those with an ALL. These may reflect adaptations in the ALC and LCL that are present to compensate for the absence of the anterolateral rotatory stability afforded by the ALL.

Acute aortic dissection (AAD) is a critical condition characterized by the tearing of the aortic wall, posing significant diagnostic challenges due to its diverse clinical presentations. We present the case of a 61-year-old male with hypertension and dyslipidemia who presented with acute abdominal and chest pain, initially raising suspicion of myocardial infarction. Despite an unremarkable electrocardiogram and initially normal troponin levels, the patient experienced ventricular fibrillation, prompting further evaluation. The patient’s clinical course was complicated by recurrent cardiac arrests. Subsequent imaging revealed AAD, which was not initially recognized, emphasizing the importance of maintaining a broad differential diagnosis and the critical need for prompt recognition and management of AAD. This case underscores the necessity of considering AAD in patients with atypical presentations and the pivotal role of advanced imaging techniques in facilitating timely diagnosis and appropriate intervention.

In this case, a 79-year-old white male is seen in the emergency department complaining of acute chest pressure, shortness of breath, diaphoresis, and dizziness that began for 4 h from the time of presentation. Physical examination showed signs concerning for cardiac tamponade in the presence of hypotension. Echocardiography showed a large amount of hemopericardium. We then injected intravenous contrast that became visible within the pericardial space. Chest computed tomography showed Type A aortic dissection. The patient was transferred to a higher-level facility for intervention. We share this rare presentation of spontaneous aortic dissection complicated by cardiac tamponade and hemopericardium.

Our case presents a 53-year-old male with type 2 diabetes and dyslipidemia presenting to the emergency department with symptoms of chest pressure, palpitations, dyspnea, and exercise intolerance. On initial imaging, an abnormal color flow signal was seen that was initially thought to be secondary to a Gerbode defect. However, using more detailed imaging, cardiac computed tomography angiography suggested the possibility of a noncoronary sinus of Valsalva aneurysm (SOVA) rupture into the right atrium, making the diagnosis challenging. Finally, transesophageal echocardiography confirmed rupture of a SOVA. This case report highlights the importance of maintaining a high index of suspicion when considering rare cardiac anomalies and emphasizes the significance of using different imaging modalities to reach an accurate diagnosis.