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Over 90% of children with Autism Spectrum Disorders (ASD) demonstrate atypical sensory behaviors. In fact, hyper- or hyporeactivity to sensory input or unusual interest in sensory aspects of the environment is now included in the DSM-5 diagnostic criteria.

This study was designed to examine factors associated with literal interpretations of homonyms. Participants were 212 second graders, ages 7;0-8;11, who listened to a story containing 16 key words. The key words were homonymous words ('pseudo-homonyms'), nonsense words, or familiar words used accurately. While listening to the story, children selected an illustration of each key word. Later, they were asked to recall the key words and to justify their picture selections. There was no association between interpretation and recall accuracy for nonsense words or familiar words used accurately; however, children who accurately recalled a homonymous key word were more likely to interpret the homonym 'literally,' relative to children who failed to recall the key word. Yet most of the children who correctly interpreted the pseudohomonyms also correctly interpreted these key words. Most children correctly recalled the story context regardless of key word type, but whereas correct recall of context predicted accurate interpretation of nonsense words and familiar words used accurately, it did not do so for homonyms. Children made equivalent numbers of literal and accurate interpretations of homonyms, even when correctly recalling context. Children's justifications for their word interpretations implicated the role of metacognitive skills, particularly in terms of selective attention, as a factor influencing homonym interpretation. [ABSTRACT FROM AUTHOR]

Macitentan is a dual endothelin receptor antagonist (ERA) approved for treating pulmonary arterial hypertension (PAH). SOPRANO evaluated the efficacy and safety of macitentan versus placebo in pulmonary hypertension (PH) patients after left ventricular assist device (LVAD) implantation. SOPRANO was a phase 2, multicenter, double-blind, randomized, placebo-controlled, parallel-group study. Patients with an LVAD implanted within the prior 90 days who had persistent PH (i.e., mean pulmonary arterial pressure ≥25 mmHg, pulmonary artery wedge pressure [PAWP] ≤18 mmHg, and pulmonary vascular resistance [PVR] >3 Wood units [WU]) were randomized (1:1) to macitentan 10 mg or placebo once daily for 12 weeks. The primary endpoint was change in PVR. Secondary endpoints included change in right-heart catheterization hemodynamic variables, N-terminal prohormone of brain natriuretic peptide levels, World Health Organization functional class, and safety/tolerability. Fifty-seven patients were randomized to macitentan ( n  = 28) or placebo ( n  = 29). A statistically significant reduction in PVR from baseline to Week 12 was observed with macitentan versus placebo (placebo-corrected geometric mean ratio, 0.74; 95% confidence interval, 0.58-0.94; p  = .0158). No statistically significant differences were observed in secondary endpoints. In a post-hoc analysis, 66.7% of patients receiving macitentan achieved PVR <3 WU versus 40.0% receiving placebo ( p  = .0383). Macitentan was generally well tolerated; adverse events were consistent with those in previous PAH studies with macitentan. In conclusion, macitentan showed promising tolerability and significantly reduced PVR in PH patients with persistently elevated PVR after LVAD implantation. ClinicalTrials. gov identifier: NCT02554903., Competing Interests: Robert P. Frantz is receiving grants and research support from United Therapeutics, Medtronic, and Gossamer Bio, and is scientific medical advisor to Altavant, ShouTi, Liquidia Corporation, Merck, Tenax Therapeutics, and Janssen Pharmaceutical Companies of Johnson & Johnson. His institution has received funding from Bayer and Gossamer Bio. Shashank S. Desai has served on the speakers’ bureau for Abbott. Gregory Ewald is on the speakers’ bureau and is a consultant with Abbott. Veronica Franco's institution receives research support from Acceleron/Merck, Gossamer, Janssen, United Therapeutics, Aerovate Therapeutics, Respira, and Cereno Scientific. Antoine Hage is receiving grants and research support from United Therapeutics, Lung LLC, Arena, Reata, and Bayer, and is a stockholder in Johnson & Johnson and Pfizer. Evelyn M. Horn's institution has received funding from Gossamer, Acceleron/Merck, Abbott, and Cereno Scientific. Stacy Mandras is a speaker and consultant for United Therapeutics and Bayer Pharmaceuticals. Myung H. Park is a scientific medical advisor with AstraZeneca. Ashwin K. Ravichandran is consulting/speaking for Abbott, Medtronic and speaking for United Therapeutics, Janssen, and Bayer; he personally receives no grants from these companies, but his institution does. Ronald Zolty is a consultant for Janssen Pharmaceutical Companies of Johnson & Johnson, Bayer, United Therapeutics, and Alnylam. Mark A. Rocco, Mona Selej, and Carol Zhao were employees of Actelion Pharmaceuticals US, Inc., South San Francisco, CA (at the time of manuscript development) and are current stockholders of Johnson & Johnson. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2024 Actelion Pharmaceuticals US, Inc. Pulmonary Circulation published by John Wiley & Sons Ltd on behalf of Pulmonary Vascular Research Institute.)

Background: Hemocompatibility-related adverse events affect patients after left ventricular assist device (LVAD) implantation but are hard to predict., Objectives: Dynamic risk modeling with a multistate model can predict risk of gastrointestinal bleeding (GIB), stroke, or death in ambulatory patients., Methods: This was a secondary analysis of the MOMENTUM 3 (Multicenter Study of MagLev Technology in Patients Undergoing Mechanical Circulatory Support Therapy with HeartMate 3) trial. HeartMate 3 LVAD recipients who survived to hospital discharge and were followed for up to 2 years. A total of 145 variables were included in the multistate model with multivariate logistic regression. Model performance was assessed with the area under the curve in a holdout validation cohort. A risk stratification tool was created by dividing patients into categories of predicted risk using the final model variables and associated OR., Results: Among 2,056 LVAD patients, the median age was 59.4 years (20.4% women, 28.6% Black). At 2 years, the incidence of GIB, stroke, and death was 25.6%, 6.0%, and 12.3%, respectively. The multistate model included 39 total variables to predict risk of GIB (16 variables), stroke (10 variables), and death (19 variables). When ambulatory patients were classified according to their risk category, the 30-day observed event rate in the highest risk group for GIB, stroke, or death was 26.9%, 1.8%, and 4.8%, respectively. The multistate model predicted GIB, stroke, and death at any 30-day period with an area under the curve of 0.70, 0.69, and 0.86, respectively., Conclusions: The multistate model informs 30-day risk in ambulatory LVAD recipients and allows recalculation of risk as new patient-specific data become available. The model allows for accurate risk stratification that predicts impending adverse events and may guide clinical decision making. (MOMENTUM 3 IDE Clinical Study Protocol; NCT02224755)., Competing Interests: Funding Support and Author Disclosures Abbott is the sponsor of the MOMENTUM 3 studies. Abbott supported an investigator-initiated grant paid to the Inova Heart and Vascular Institute to support this effort; and Abbott has filed a U.S. provisional patent (U.S. Patent Application No. 63/421,450) for the work presented in the paper. Dr Shah is supported by National Institutes of Health K23 Career Development Award 1K23HL143179; has received consulting fees from Procyrion, Merck, and Natera; and grant support has been paid to his institution from Abbott, Roche, Merck, and Bayer. Dr Sayer has received consulting fees from Abbott. Dr Kanwar is on the medical advisory board for Abiomed, CorWave, and CareDx. Dr Cowger has served as a consultant for Abbott, Medtronic, Bioventrix, Endotronix, Bivacor, and Procyrion; and has received grant support and speaker fees from Abbott. Dr Pagani has served as an AD hoc scientific advisor without compensation for FineHeart, Medtronic, CH Biomedical, and Abbott; has served as medical monitor for Abiomed; is a member of the data safety monitoring board for Carmat and the National Heart, Lung, and Blood Institute PumpKIN clinical trial; and is Chair of the Society of Thoracic Surgeons Intermacs Task Force. Dr Mehra has received travel support and consulting fees, paid to Brigham and Women’s Hospital, from Abbott; has received fees for serving on a steering committee from Medtronic and Janssen (Johnson and Johnson); has received fees for serving on a data and safety monitoring board from Mesoblast; has received consulting fees from Natera, Paragonix, Moderna, Baim Institute of Clinical Research, and Broadview Ventures; and has received fees for serving as a scientific board member from NuPulseCV, Leviticus, and FineHeart. Dr Cleveland has received fees from Abbott and Medtronic. Dr Desai is on the Speakers Bureau for Abbott. Drs Lu, Hu, Connolly, and Kormos are employees of Abbott. Dr Uriel is a medical advisory board member for Livemetric, Levitcus, and Revamp; and receives grant support from Abbott, Abiomed, and Fire 1. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: The purpose of this study is to compare 30-day perioperative outcomes following treatment of intertrochanteric (IT) fractures with intramedullary nail (IMN), total hip arthroplasty (THA), or hemiarthroplasty (HA)., Methods: Using the National Surgical Quality Improvement Program database, we conducted a retrospective cohort study of patients who had sustained an IT fracture treated with primary IMN, THA, or HA between 2017 and 2020. International Classification of Diseases, 10th Revision codes S72.141-S72.146, subtypes A through C, were used to identify eligible patients and were cross-referenced to primary Current Procedural Terminology codes, used to identify the following procedure types: 27245: IMN; 27130: THA; and 27236: HA. Revision cases and patients who underwent arthroplasty for osteoarthritis were excluded. Outcomes of interest included reoperation, readmission, operative time, length of stay, and major and minor complications. Multivariate regression was used to evaluate differences in postoperative outcomes between groups., Results: There were 29,809 IT fractures treated with IMN (94.6%), 1493 treated with HA (4.7%), and 217 treated with THA (0.70%). There was a statistically significant increase in 30-day reoperation rates (adjusted odds ratio [aOR] = 1.99 [95% confidence interval = 1.51, 2.63], P < .001) when combining all arthroplasty patients compared to IMN. There was no statistically significant difference in the overall complication rate between IMN (13.58%) and HA (14.60%, aOR = 1.09, P  = .315) or THA (11.98%, aOR = 1.00, P  = .998). When compared to IMN (0.12%), there was a statistically significantly decreased need for transfusion in the HA group (aOR = 0.71 [95% confidence interval = 0.61, 0.80], P < .001)., Conclusions: Primary HA is associated with an increased 30-day reoperation rate and decreased need for blood transfusion, but there were no other significant differences in postoperative morbidity identified among IMN, THA, and HA in the treatment of IT fractures. Given the challenges and inferior outcomes associated with conversion arthroplasty, the lack of significant difference in morbidity between the 3 groups suggests that primary arthroplasty may be a safe and viable treatment option in selected patients with IT fractures. Comparative studies with longer clinical follow-up will be necessary to establish the appropriate indications and further evaluate the clinical outcomes of primary arthroplasty in the treatment of IT fractures., (© 2024 The Authors.)

The process of Ag receptor diversity is initiated by RAGs consisting of RAG1 and RAG2 in developing lymphocytes. Besides its role as a sequence-specific nuclease during V(D)J recombination, RAGs can also act as a structure-specific nuclease leading to genome instability. Thus, regulation of RAG expression is essential to maintaining genome stability. Previously, the role of miR29c in the regulation of RAG1 was identified. In this article, we report the regulation of RAG1 by miR-29a in the lymphocytes of both mice (Mus musculus) and humans (Homo sapiens). The level of RAG1 could be modulated by overexpression of miR-29a and inhibition using anti-miRs. Argonaute2-immunoprecipitation and high-throughput sequencing of RNA isolated by crosslinking immunoprecipitation studies established the association of miR-29a and RAG1 with Argonaute proteins. We observed a negative correlation between miR-29a and RAG1 levels in mouse B and T cells and leukemia patients. Overexpression of pre-miR-29a in the bone marrow cells of mice led to the generation of mature miR-29a transcripts and reduced RAG1 expression, which led to a significant reduction in V(D)J recombination in pro-B cells. Importantly, our studies are consistent with the phenotype reported in miR-29a knockout mice, which showed impaired immunity and survival defects. Finally, we show that although both miR-29c and miR-29a can regulate RAG1 at mRNA and protein levels, miR-29a substantially impacts immunity and survival. Our results reveal that the repression of RAG1 activity by miR-29a in B cells of mice and humans is essential to maintain Ig diversity and prevent hematological malignancies resulting from aberrant RAG1 expression in lymphocytes., (Copyright © 2024 by The American Association of Immunologists, Inc.)

Aims: Despite significant morbidity and mortality, recent advances in cardiogenic shock (CS) management have been associated with increased survival. However, little is known regarding the management of patients who survive CS with heart failure (HF) with reduced left ventricular ejection fraction (LVEF, HFrEF), and the utilization of guideline-directed medical therapy (GDMT) in these patients has not been well described. To fill this gap, we investigated the use of GDMT during an admission for CS and short-term outcomes using the Inova single-centre shock registry., Methods: We investigated the implementation of GDMT for patients who survived an admission for CS with HFrEF using data from our single-centre shock registry from January 2017 to December 2019. Baseline characteristics, discharge clinical status, data on GDMT utilization and 30 day, 6 month and 12 month patient outcomes were collected by retrospective chart review., Results: Among 520 patients hospitalized for CS during the study period, 185 (35.6%) had HFrEF upon survival to discharge. The median age was 64 years [interquartile range (IQR) 56, 70], 72% (n = 133) were male, 22% (n = 40) were Black and 7% (n = 12) were Hispanic. Forty-one per cent of patients (n = 76) presented with shock related to acute myocardial infarction (AMI), while 59% (n = 109) had HF-related CS (HF-CS). The median length of hospital stay was 12 days (IQR 7, 18). At discharge, the proportions of patients on beta-blockers, angiotensin-converting enzyme inhibitors (ACEis)/angiotensin receptor blockers (ARBs)/angiotensin receptor/neprilysin inhibitors (ARNIs) and mineralocorticoid receptor antagonists (MRAs) were 78% (n = 144), 58% (n = 107) and 55% (n = 101), respectively. Utilization of three-drug GDMT was 33.0% (n = 61). Ten per cent of CS survivors with HFrEF (n = 19) were not prescribed any component of GDMT at discharge. Multivariable logistic regression adjusted for baseline GDMT use revealed that patients with lower LVEF and those who transferred to our centre from an outside hospital were more likely to experience GDMT addition (P < 0.05). Patients prescribed at least one additional class of GDMT during admission had higher odds of 6 month and 1 year survival (P < 0.01): On average, 6 month survival odds were 7.1 times greater [confidence interval (CI) 1.9, 28.5] and 1 year survival odds were 6.0 times greater than those who did not have at least one GDMT added (CI 1.9, 20.5)., Conclusions: Most patients who survived CS admission with HFrEF in this single-centre CS registry were not prescribed all classes or goal doses of GDMT at hospital discharge. These findings highlight an urgent need to augment multidisciplinary efforts to enhance the post-discharge medical management and outcomes of patients who survive CS with HFrEF., (© 2024 The Author(s). ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Purpose: To systematically review the literature regarding the biomechanical properties of different repair techniques and fixation methods for vertically oriented meniscal tears., Methods: Human cadaveric studies evaluating the biomechanical properties of different repair techniques for vertically oriented meniscal tears were identified using the PubMed, EMBASE, and Cumulative Index to Nursing & Allied Health databases. Primary outcomes included load to failure, displacement, stiffness, peak contact pressure, and contact area of repaired menisci. Repair techniques from included studies were reclassified into a total of 19 distinct all-inside (AI), inside-out (IO), or outside-in (OI) techniques., Results: Sixteen studies were included (420 total menisci). Contact pressure and area were restored to intact-state values across all 5 compressive load studies at low knee flexion angles but not at greater knee flexion angles (i.e., >60°). There were no significant differences in contact pressure or area between AI, IO, and OI techniques across all studies. Some studies demonstrated statistically significant advantages in tensile properties with IO techniques when compared with AI techniques, whereas others found AI techniques to be superior. No studies directly compared tensile properties of OI techniques with those of AI or IO techniques. Vertical mattress suture configurations resulted in significantly greater load to failure and decreased displacement compared with horizontal mattress configurations in 67% of studies comparing the 2 techniques. There was no difference in the rate of tissue failure in AI (66.97%), IO (60.38%), or OI (66.67%, χ 2  = 0.83, P = .66) techniques., Conclusions: Contact mechanics are reliably restored after repair of vertical meniscal tears at low flexion angles but inconsistently restored at greater flexion angles, regardless of technique. Vertical mattress configurations outperformed horizontal mattress configurations under tensile load. There are conflicting data regarding the comparison of tensile properties between AI and IO techniques. Ultimately, neither AI, IO, nor OI repair demonstrated superior biomechanical properties in the present literature., Clinical Relevance: Several repair techniques demonstrate favorable biomechanical properties for vertical meniscal tears under tensile and compressive loads. Neither AI, IO, nor OI repair techniques demonstrate superior biomechanical properties at this time., Competing Interests: Disclosures The authors report the following potential conflicts of interest or sources of funding: J.C. reports other from the American Orthopaedic Society for Sports Medicine, AANA, and International Society of Arthroscopy, Knee Surgery and Orthopaedic Sports Medicine; personal fees from Arthrex, Conmed Linvatec, Ossur, and Smith & Nephew, outside the submitted work. All other authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Full ICMJE author disclosure forms are available for this article online, as supplementary material., (Copyright © 2024 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.)

Background: Although internal medicine (IM) physicians accept public advocacy as a professional responsibility, there is little evidence that IM training programs teach advocacy skills. The prevalence and characteristics of public advocacy curricula in US IM residency programs are unknown., Objectives: To describe the prevalence and characteristics of curricula in US IM residencies addressing public advocacy for communities and populations; to describe barriers to the provision of such curricula., Design: Nationally representative, web-based, cross-sectional survey of IM residency program directors with membership in an academic professional association., Participants: A total of 276 IM residency program directors (61%) responded between August and December 2022., Main Measurements: Percentage of US IM residency programs that teach advocacy curricula; characteristics of advocacy curricula; perceptions of barriers to teaching advocacy., Key Results: More than half of respondents reported that their programs offer no advocacy curricula (148/276, 53.6%). Ninety-five programs (95/276, 34.4%) reported required advocacy curricula; 33 programs (33/276, 12%) provided curricula as elective only. The content, structure, and teaching methods of advocacy curricula in IM programs were heterogeneous; experiential learning in required curricula was low (23/95, 24.2%) compared to that in elective curricula (51/65, 78.5%). The most highly reported barriers to implementing or improving upon advocacy curricula (multiple responses allowed) were lack of faculty expertise in advocacy (200/276, 72%), inadequate faculty time (190/276, 69%), and limited curricular flexibility (148/276, 54%)., Conclusion: Over half of US IM residency programs offer no formal training in public advocacy skills and many reported lack of faculty expertise in public advocacy as a barrier. These findings suggest many IM residents are not taught how to advocate for communities and populations. Further, less than one-quarter of required curricula in public advocacy involves experiential learning., (© 2024. The Author(s), under exclusive licence to Society of General Internal Medicine.)

Objective: The study aimed to characterize the experiences of primary caregivers of children with medical complexity (CMC) in engaging with other members of the child's caregiving network, thereby informing the design of health information technology (IT) for the caregiving network. Caregiving networks include friends, family, community members, and other trusted individuals who provide resources, information, health, or childcare., Materials and Methods: We performed a secondary analysis of two qualitative studies. Primary studies conducted semi-structured interviews (n = 50) with family caregivers of CMC. Interviews were held in the Midwest (n = 30) and the mid-Atlantic region (n = 20). Interviews were transcribed verbatim for thematic analysis. Emergent themes were mapped to implications for the design of future health IT., Results: Thematic analysis identified 8 themes characterizing a wide range of primary caregivers' experiences in constructing, managing, and ensuring high-quality care delivery across the caregiving network., Discussion: Findings evidence a critical need to create flexible and customizable tools designed to support hiring/training processes, coordinating daily care across the caregiving network, communicating changing needs and care updates across the caregiving network, and creating contingency plans for instances where caregivers are unavailable to provide care to the CMC. Informaticists should additionally design accessible platforms that allow primary caregivers to connect with and learn from other caregivers while minimizing exposure to sensitive or emotional content as indicated by the user., Conclusion: This article contributes to the design of health IT for CMC caregiving networks by uncovering previously underrecognized needs and experiences of CMC primary caregivers and drawing direct connections to design implications., (© The Author(s) 2024. Published by Oxford University Press on behalf of the American Medical Informatics Association. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Cardiogenic shock (CS) is a time-sensitive and hemodynamically complex syndrome with a broad spectrum of etiologies and clinical presentations. Despite contemporary therapies, CS continues to maintain high morbidity and mortality ranging from 35 to 50%. More recently, burgeoning observational research in this field aimed at enhancing the early recognition and characterization of the shock state through standardized team-based protocols, comprehensive hemodynamic profiling, and tailored and selective utilization of temporary mechanical circulatory support devices has been associated with improved outcomes. In this narrative review, we discuss the pathophysiology of CS, novel phenotypes, evolving definitions and staging systems, currently available pharmacologic and device-based therapies, standardized, team-based management protocols, and regionalized systems-of-care aimed at improving shock outcomes. We also explore opportunities for fertile investigation through randomized and non-randomized studies to address the prevailing knowledge gaps that will be critical to improving long-term outcomes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The handling editor LC declared a past co-authorship with the authors CR, SD, MP., (© 2024 Mehta, Vavilin, Nguyen, Batchelor, Blumer, Cilia, Dewanjee, Desai, Desai, Flanagan, Isseh, Kennedy, Klein, Moukhachen, Psotka, Raja, Rosner, Shah, Tang, Truesdell, Tehrani and Sinha.)

One of the primary reasons behind the pathogenesis of T cell acute lymphoblastic leukemia (T-ALL) is the deregulation of the transcription factor BCL11B . The exon 4 of BCL11B harbors several driver mutations, which abolishes its DNA-binding ability. The high frequency of C > T or G > A conversion in close vicinity of AID (Activation-induced cytidine deaminase)-hotspot motifs in the deregulated gene prompted us to investigate the role of AID in BCL11B mutagenesis. Our results reveal that AID is expressed in T-ALL patient-derived cells, binds to BCL11B fragile region (FR) in exon 4 of T cells in vivo, and generates a signature mutation pattern in this region. The mutation frequency in BCL11B FR could be modulated upon overexpression of the AID gene in the knockout background, further suggesting the involvement of AID in BCL11B mutagenesis. Importantly, various lines of experimentation reveal that BCL11B FR could fold into parallel G-quadruplex, triplex, and hairpin structures, which could act as a replication/transcription block, causing mutagenesis. Thus, our results suggest that AID binds to BCL11B exon 4 due to non-B DNA formation, causing U:G mismatches or replication blocks, which, when repaired erroneously, generates deleterious mutations, resulting in loss of functionality of BCL11B , and thus becomes the cause of T-ALL.

Background: The purpose of this study is to provide a systematic review of the literature pertaining to Patient-Reported Outcome Measurement Information System (PROMIS) validation and utilization as an outcomes metric in total knee arthroplasty (TKA) patients. This is the first systematic review on PROMIS use in total knee arthroplasty patients., Methods: A systematic search of the Pubmed/MEDLINE and Embase databases was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Study characteristics, patient demographics, psychometric properties (Pearson and Spearman correlation) with legacy patient-reported outcome measurement (PROM) instruments, floor and ceiling effects, responsiveness, and minimum clinically important difference (MCID) and PROMIS outcomes were recorded and analyzed., Results: Fifteen studies investigating PROMIS in 11,140 patients were included. The weighted-average Pearson correlation coefficient comparing PROMIS domains with legacy patient-reported outcome measurements in total knee arthroplasty patients was 0.62 [standard error (SE) = 0.06] and the weighted-average Spearman correlation comparing PROMIS domains with legacy patient-reported outcome measurements in total knee arthroplasty patients was 0.59 (SE = 0.06), demonstrating moderate-to-strong correlation and validity. There were no differences in weighted average floor [0.03% (SE = 3.1) versus 0% (SE = 0.1) versus 0.01% (SE = 1.1); p = 0.25] or ceiling effects [0.01% (SE = 0.7) versus 0.02% (SE = 1.4) versus 0.04% (SE = 3.5); p = 0.36] between PROMIS and legacy instruments. The weighted average for percentage of patients achieving MCID was 59.1% for global physical health (GPH), 26.0% for global mental health (GMH), 52.7% for physical function (PF), 67.2% for pain interference (PI), and 37.2% for depression., Conclusion: Notably, PROMIS global physical health, physical function, and pain interference were found to be significantly responsive, with PROMIS pain interference most effectively capturing clinical improvement as evidenced by the achievement of MCID., (© 2023. The Author(s).)

t(8;14) translocation is the hallmark of Burkitt's lymphoma and results in c-MYC deregulation. During the translocation, c-MYC gene on chromosome 8 gets juxtaposed to the Ig switch regions on chromosome 14. Although the promoter of c-MYC has been investigated for its mechanism of fragility, little is known about other c-MYC breakpoint regions. We have analyzed the translocation break points at the exon 1/intron 1 of c-MYC locus from patients with Burkitt's lymphoma. Results showed that the breakpoint region, when present on a plasmid, could fold into an R-loop confirmation in a transcription-dependent manner. Sodium bisulfite modification assay revealed significant single-strandedness on chromosomal DNA of Burkitt's lymphoma cell line, Raji, and normal lymphocytes, revealing distinct R-loops covering up to 100 bp region. Besides, ChIP-DRIP analysis reveals that the R-loop antibody can bind to the breakpoint region. Further, we show the formation of stable parallel intramolecular G-quadruplex on non-template strand of the genome. Finally, incubation of purified AID in vitro or overexpression of AID within the cells led to enhanced mutation frequency at the c-MYC breakpoint region. Interestingly, anti-γH2AX can bind to DSBs generated at the c-MYC breakpoint region within the cells. The formation of R-loop and G-quadruplex was found to be mutually exclusive. Therefore, our results suggest that AID can bind to the single-stranded region of the R-loop and G4 DNA, leading to the deamination of cytosines to uracil and induction of DNA breaks in one of the DNA strands, leading to double-strand break, which could culminate in t(8;14) chromosomal translocation., Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the content of this article., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Ice hockey is a fast-paced contact sport with a high rate of injury. While many of the injuries are acute and related to high skating speeds, frequent collisions, and sharp skates, the clinician must also be aware of the chronic injuries that commonly arise from playing this sport. The "Bauer bump" is one such chronic injury, which is the onset of Haglund syndrome in ice hockey players occurring in the context of wearing ice hockey skates. With this condition, players notice a bony enlargement of their posterosuperior calcaneus with or without the accompanying symptoms of retrocalcaneal bursitis and insertional Achilles tendinopathy. It is important for clinicians to understand the nature of Haglund syndrome in hockey players so that it can be appropriately diagnosed, managed, and ultimately, prevented.

Solitary fibrous tumor (SFT) is a rare mesenchymal tumor of fibroblastic origin commonly occurring in pleura. It can occur at many extrapleural sites but is rare in orbit. Most cases are benign and recurrence is not unusual in the head and neck and orbit and is usually due to incomplete surgical excision. However, malignant transformation (MT) in orbital SFT is extremely unusual. We present a case of orbital SFT in adult male who developed recurrence with MT eight years after initial surgical excision. He underwent left orbital exenteration. The recurrent tumor revealed features of malignancy with areas exhibiting morphology typical of SFT. The immunochemistry confirmed the diagnosis of SFT with MT. The patient was given adjuvant radiation and was disease free for the last 18 months. Identification of malignancy in orbital SFT is important for the patient to receive appropriate postoperative treatment, as seen in the present case.

Career selection in medicine is a complex and underexplored process. Most medical career studies performed in the U.S. focused on the effect of demographic variables and medical education debt on career choice. Considering ongoing U.S. physician workforce shortages and the trilateral adaptive model of career decision making, a robust assessment of professional attitudes and work-life preferences is necessary. The objective of this study was to explore and define the dominant viewpoints related to career choice selection in a cohort of U.S. IM residents. We administered an electronic Q-sort in which 218 IM residents sorted 50 statements reflecting the spectrum of opinions that influence postgraduate career choice decisions. Participants provided comments that explained the reasoning behind their individual responses. In the final year of residency training, we ascertained participating residents' chosen career. Factor analysis grouped similar sorts and revealed four distinct viewpoints. We characterized the viewpoints as "Fellowship-Bound-Academic," "Altruistic-Longitudinal-Generalist," "Inpatient-Burnout-Aware," and "Lifestyle-Focused-Consultant." There is concordance between residents who loaded significantly onto a viewpoint and their ultimate career choice. Four dominant career choice viewpoints were found among contemporary U.S. IM residents. These viewpoints reflect the intersection of competing priorities, personal interests, professional identity, socio-economic factors, and work/life satisfaction. Better appreciation of determinants of IM residents' career choices may help address workforce shortages and enhance professional satisfaction., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)

Purpose: To identify risk factors for rupture, and to determine outcomes of endovascular treatment of median arcuate ligament (MAL) compression-related visceral artery aneurysms (VAAs)., Methods and Materials: A retrospective review of patients who presented with MALC-related VAAs was performed from 1999 to 2021. A total of 21 patients (12 men) and 39 VAAs associated with MAL compression were encountered (mean age, 59 years). Imaging studies were reviewed for the number, morphology/size, and recurrence of aneurysms. Statistical analysis was performed to identify risk factors for rupture., Results: Ten patients presented with acute rupture, and 12 patients were symptomatic with nonspecific abdominal pain. Twenty-two aneurysms were fusiform in morphology and 17 aneurysms were saccular in morphology. Of the 14 aneurysms that presented with acute hemorrhage, 12 (86%) were fusiform in morphology (odds ratio, 9.0; P < .01). The mean aneurysm size was 1.3 cm, and the mean ruptured size was 0.6 cm. Thirty-one aneurysms were treated by endovascular techniques, and technical success was achieved in all cases. Fourteen patients were found to have an Arc of Buhler. No procedure-related adverse events occurred. No patient underwent surgical ligament release. The mean time of follow-up was 3.2 years, and no aneurysms recurred after endovascular treatment., Conclusions: MAL compression-associated VAAs are an important clinical entity that should be treated even at small sizes, particularly if they are fusiform in morphology. Endovascular therapy is safe and feasible and results in durable aneurysm exclusion., (Copyright © 2023 SIR. Published by Elsevier Inc. All rights reserved.)

Background: Textbook knowledge and clinical dogma are often insufficient for effective evidence-based decision making when treating musculoskeletal injuries in American football players, given the variability in presentation and outcomes across different sports and different levels of competition. Key evidence can be drawn directly from high-quality published articles to make the appropriate decisions and recommendations for each athlete's unique situation., Purpose: To identify and analyze the 50 most cited articles related to football-related musculoskeletal injury to provide an efficient tool in the arsenal of trainees, researchers, and evidence-based practitioners alike., Study Design: Cross-sectional study., Methods: The ISI Web of Science and SCOPUS databases were queried for articles pertaining to musculoskeletal injury in American football. For each of the top 50 most cited articles, bibliometric elements were evaluated: citation count and density, decade of publication, journal, country, multiple publications by the same first author or senior author, article content (topic, injury area), and level of evidence (LOE)., Results: The mean ± SD number of citations was 102.76 ± 37.11; the most cited article, with 227 citations, was "Syndesmotic Ankle Sprains" published in 1991 by Boytim et al. Several authors served as a first or senior author on >1 publication, including J.S. Torg (n = 6), J.P. Bradley (n = 4), and J.W. Powell (n = 4). The American Journal of Sports Medicine published the majority of the 50 most cited articles (n = 31). A total of 29 articles discussed lower extremity injuries, while only 4 discussed upper extremity injuries. The majority of the articles (n = 28) had an LOE of 4, with only 1 article having an LOE of 1. The articles with an LOE of 3 had the highest mean citation number (133.67 ± 55.23; F = 4.02; P = .05)., Conclusion: The results of this study highlight the need for more prospective research surrounding the management of football-related injury. The low overall number of articles on upper extremity injury (n = 4) also highlights an area for further research., Competing Interests: One or more of the authors has declared the following potential conflict of interest or source of funding: H.W.S. has received education payments from Medwest and Smith & Nephew. C.A.P. has received education payments from Arthrex. AOSSM checks author disclosures against the Open Payments Database (OPD). AOSSM has not conducted an independent investigation on the OPD and disclaims any liability or responsibility relating thereto. Ethical approval was not sought for the present study., (© The Author(s) 2023.)

Patient-Reported Outcome Measurement Information System (PROMIS) has favorable psychometric and administrative properties in orthopaedic clinical research. It facilitates clinically meaningful data collection while minimizing administration time and survey fatigue and improving compliance. PROMIS is a critical component of patient-centered care and shared decision making, as it provides enhanced communication and engagement between patients and providers. As a validated instrument, it may also aid in measuring value-based health care quality. The goal of the current work is to provide an overview of PROMIS metrics used in orthopaedic foot and ankle, including advantages and disadvantages compared to legacy scales and PROMIS's applicability in specific foot and ankle conditions based on psychometric properties. We provide a review of the literature regarding the utilization of PROMIS as an outcome measure for specific foot and ankle procedures and conditions.

Purpose: The purpose of this study was to compare patient-reported outcomes and return to play (RTP) rates following ulnar collateral ligament reconstruction (UCLR) in patients with and without posteromedial elbow impingement (PI) treated with concomitant arthroscopic posteromedial osteophyte resection., Methods: Baseball players who underwent UCLR performed by the senior surgeon with minimum follow-up of 2 years were surveyed in this retrospective cohort study. Primary outcomes included Kerlan-Jobe Orthopaedic Clinic Shoulder and Elbow (KJOC) score, Andrews-Timmerman score, and RTP rate. Secondary outcomes included patient satisfaction scores., Results: 35 baseball players were included. Eighteen had no preoperative impingement (mean age: 19.06 ± 3.28 years), while 17 had PI treated with concomitant arthroscopic osteophyte resection (mean age: 20.06 ± 2.68 years). Following surgery, there was no difference in mean Andrews-Timmerman score (no impingement = 91.67 ± 8.04 vs PI = 92.06 ± 7.92, P = .89) nor KJOC score (no impingement = 83.36 ± 11.72 vs PI = 79.88 ± 12.35, P = .40), but there was a decreased mean KJOC throwing control sub-score in the PI group (7.65 ± 2.40 vs 9.11 ± 1.32, P = .04). There was no difference in RTP rate between the groups (no impingement = 72.22%, PI = 94.12%, χ 2  = 1.28; P  = .26). There was significantly higher mean satisfaction score in the no impingement group (96.67 ± 4.58 vs 90.12 ± 11.91; P  = .04), and those patients were also more likely to pursue surgical treatment again (94.44% vs 52.94%, χ 2  = 7.88; P  = .005)., Conclusions: There was no difference in RTP rate following ulnar collateral ligament reconstruction in baseball players with and without posteromedial impingement treated with arthroscopic resection. Outcomes on the KJOC and Andrews-Timmerman scores were good to excellent in both groups. Players in the posteromedial impingement group were less satisfied with their outcome, however, and less likely to elect for surgery if they were to sustain the injury again. Additionally, players in the posteromedial impingement group were found to have decreased throwing control on the KJOC questionnaire, which may suggest that the presence of posteromedial osteophytes represent adaptive changes to stabilize the elbow while throwing., Level of Evidence: Level III, retrospective cohort study., (© 2023 The Authors.)

Introduction: Acute leukemia is a heterogeneous disease with distinct genotypes and complex karyotypes leading to abnormal proliferation of hematopoietic cells. According to GLOBOCAN reports, Asia accounts for 48.6% of leukemia cases, and India reports ~10.2% of all leukemia cases worldwide. Previous studies have shown that the genetic landscape of AML in India is significantly different from that in the western population by WES. Methods: We have sequenced and analyzed 9 acute myeloid leukemia (AML) transcriptome samples in the present study. We performed fusion detection in all the samples and categorized the patients based on cytogenetic abnormalities, followed by a differential expression analysis and WGCNA analysis. Finally, Immune profiles were obtained using CIBERSORTx. Results: We found a novel fusion HOXD11-AGAP3 in 3 patients, BCR-ABL1 in 4, and KMT2A-MLLT3 in one patient. Categorizing the patients based on their cytogenetic abnormalities and performing a differential expression analysis, followed by WGCNA analysis, we observed that in the HOXD11-AGAP3 group, correlated co-expression modules were enriched with genes from pathways like Neutrophil degranulation, Innate Immune system, ECM degradation, and GTP hydrolysis. Additionally, we obtained HOXD11-AGAP3-specific overexpression of chemokines CCL28 and DOCK2. Immune profiling using CIBRSORTx revealed differences in the immune profiles across all the samples. We also observed HOXD11-AGAP3-specific elevated expression of lincRNA HOTAIRM1 and its interacting partner HOXA2. Discussion: The findings highlight population-specific HOXD11-AGAP3, a novel cytogenetic abnormality in AML. The fusion led to alterations in immune system represented by CCL28 and DOCK2 over-expression. Interestingly, in AML, CCL28 is known prognostic marker. Additionally, non-coding signatures (HOTAIRM1) were observed specific to the HOXD11-AGAP3 fusion transcript which are known to be implicated in AML., Competing Interests: Authors AP, NO, and SJ are employed by HealthCare Global Enterprises Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Desai, Ravindran, Panchal, Ojha, Jadhav and Choudhary.)

Competing Interests: Disclosures The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Background: Ulnar collateral ligament (UCL) reconstruction has received a unique level of attention in the press and social media. There has also been an increasing use of the internet by patients to seek medical information. Concern exists regarding the quality and comprehensibility of online information when used for patient education., Purpose: To evaluate the quality and comprehensibility of the most-viewed YouTube videos related to the diagnosis and management of UCL injuries. Based on our new evidence-based scoring rubrics, we hypothesized that the quality and comprehensibility of these videos would be poor., Study Design: Cross-sectional study., Methods: The YouTube platform was searched on September 7, 2021, with the terms "UCL injury," "ulnar collateral ligament injury," "UCL surgery," "ulnar collateral ligament surgery," and "Tommy John surgery," and the 50 most-viewed videos from each search were compiled, yielding 250 videos. After removal of duplicates and application of exclusion criteria, the 100 most-viewed videos remained. Basic attributes, including duration of video and number of views, were recorded. Each video was then analyzed by 2 independent reviewers and evaluated for 4 key parameters (quality of diagnostic content [QAR-D], quality of treatment content [QAR-T], presence of inaccurate information, and comprehensibility) and graded on a novel scale from 1 to 4 (4 being the most appropriate for patient education)., Results: The mean QAR-D was 4.83 ± 3.41 (fair quality), and the mean QAR-T was 2.76 ± 3.26 (poor quality). Physician-led educational videos had both the highest mean QAR-D (6.37) and the highest mean QAR-T (4.34). No correlation was observed between video quality and views/likes. A total of 12 videos included ≥1 inaccuracy. The mean comprehensibility score was 2.66 ± 1.12, with 39 videos falling below the acceptable comprehensibility threshold (score <3)., Conclusion: The overall quality of UCL injury-related YouTube content was low. In addition, the absence of correlation between video quality and views/likes suggests that patients are not preferentially utilizing the limited high-quality content that does exist on the YouTube platform. In addition, inaccurate videos were prevalent (12%), and almost half of all videos were deemed inappropriate for patient education in terms of comprehensibility, as defined by our comprehensibility parameter., Competing Interests: One or more of the authors has declared the following potential conflict of interest or source of funding: C.A.P. has received education payments from Arthrex. C.S.A. has received consulting fees, nonconsulting fees, and royalties from Arthrex. AOSSM checks author disclosures against the Open Payments Database (OPD). AOSSM has not conducted an independent investigation on the OPD and disclaims any liability or responsibility relating thereto., (© The Author(s) 2023.)

Purpose: Robotic-assisted total knee arthroplasty typically necessitates use of tracking pins, which can vary in diameter. Complications such as infections and fractures at the pin-site have been observed, but clarification of the effect of pin diameter on complication is needed. The aim of this study is to compare the pin-related complication rates following robotic-assisted total knee arthroplasty between 4.5 mm and 3.2 mm diameter pins., Methods: In this retrospective cohort study, 90-day pin-site complication rates after robotic-assisted total knee arthroplasty were compared between 4.5 mm diameter and 3.2 mm diameter groups. In total, 367 patients were included: 177 with large pin diameter and 190 with small pin diameter. All four pin sites were evaluated using postoperative radiographs. Cases without orthogonal views or visualization of all four pin tracts were noted. Multivariate logistic regression was used to control for age, which differed between the two cohorts., Results: The rate of pin-site complications was 5.6% in the large pin diameter cohort and 2.6% in the small pin diameter cohort, with no statistically significant difference between the groups. The adjusted odds ratio for complications in small compared to large diameter group was 0.48, with a p-value of 0.18. The most common pin-site complication was infection/persistent drainage, found in 1.9% of patients, followed by intraoperative fracture of the second cortex in 1.4%. Intraoperative fracture could not be ruled out in 96 cases due to inadequate radiographic visualization of all pin sites. There was one postoperative pin-site fracture in the large diameter cohort, which required operative fixation., Conclusion: This study demonstrates no statistically significant difference in pin-site complication rates after robotic-assisted total knee arthroplasty between 4.5 mm and 3.2 mm pin diameter cohorts, although there was a trend towards increased intraoperative and postoperative pin-site fractures in the 4.5 mm group., (© 2023. The Author(s).)

Patient reported outcome measures (PROMs) are essential for clinical research and patient-centric care because they allow us to capture patient perspectives on their health condition. In knee arthroplasty, PROMs are frequently used to assess the risks and benefits of new interventions, surgical approaches, and other management strategies. A few examples of PROMs used in total knee arthroplasty (TKA) include the Oxford Knee Score (OKS), Knee Injury and Osteoarthritis Outcome Score (KOOS), and the Forgotten Joint Score (FJS) (collectively referred to as "legacy" PROMs). More recently, attention has been brought to another PROM called the Patient-Reported Outcomes Measurement Information System (PROMIS). PROMIS was developed by the National Institute of Health (NIH) and has over 300 domains assessing various aspects of patient health, including pain, physical function, and mental health. With the use of PROMIS increasing in TKA literature, there is a need to review the advancements being made in understanding and applying PROMIS for this population. Thus, the purpose of this study is to provide insight on the utilization, advantages, and disadvantages of PROMIS within the field of knee arthroplasty and to provide a comparison to legacy PROMs., (© 2023. The Author(s).)

A spinal cord injury (SCI) is a very debilitating condition causing loss of sensory and motor function as well as multiple organ failures. Current therapeutic options like surgery and pharmacotherapy show positive results but are incapable of providing a complete cure for chronic SCI symptoms. Tissue engineering, including neuroprotective or growth factors, stem cells, and biomaterial scaffolds, grabs attention because of their potential for regeneration and ability to bridge the gap in the injured spinal cord (SC). Preclinical studies with tissue engineering showed functional recovery and neurorestorative effects. Few clinical trials show the safety and efficacy of the tissue engineering approach. However, more studies should be carried out for potential treatment modalities. In this review, we summarize the pathophysiology of SCI and its current treatment modalities, including surgical, pharmacological, and tissue engineering approaches following SCI in preclinical and clinical phases., (© 2022. The Author(s), under exclusive license to Springer Nature Switzerland AG.)

Chromosomal translocations are considered as one of the major causes of lymphoid cancers. RAG complex, which is responsible for V(D)J recombination, can also cleave non-B DNA structures and cryptic RSSs in the genome leading to chromosomal translocations. The mechanism and factors regulating the illegitimate function of RAGs resulting in oncogenesis are largely unknown. Upon in silico analysis of 3760 chromosomal translocations from lymphoid cancer patients, we find that 93% of the translocation breakpoints possess adjacent cryptic nonamers (RAG binding sequences), of which 77% had CpGs in proximity. As a proof of principle, we show that RAGs can efficiently bind to cryptic nonamers present at multiple fragile regions and cleave at adjacent mismatches generated to mimic the deamination of CpGs. ChIP studies reveal that RAGs can indeed recognize these fragile sites on a chromatin context inside the cell. Finally, we show that AID, the cytidine deaminase, plays a significant role during the generation of mismatches at CpGs and reconstitute the process of RAG-dependent generation of DNA breaks both in vitro and inside the cells. Thus, we propose a novel mechanism for generation of chromosomal translocation, where RAGs bind to the cryptic nonamer sequences and direct cleavage at adjacent mismatch generated due to deamination of meCpGs or cytosines., Competing Interests: The authors have declared that no competing interests exist.