Citations

Background/objectives: Falls are a leading cause of traumatic injury and hospitalization for adults over the age of 65. While common, bed-related falls are relatively understudied when compared to ambulatory falls. The aim of this study is to characterize the risk factors for the hospitalization of older adults presenting to U.S. emergency departments (EDs) after a fall from bed. Methods: This was a cross-sectional study using publicly available data from the U.S. Consumer Product Safety Commission’s National Electronic Injury Surveillance System (NEISS) from 2014 to 2023, including all adults over the age of 65 presenting to the NEISS’s participating EDs with bed-related fall injuries. We identified fall injuries using a keyword search of the NEISS narratives and determined how the fall occurred by manually reviewing a randomized 3% sample of the narratives. We summarized demographics and injury patterns with descriptive statistics. We constructed a multivariable logistic regression model to identify risk factors for hospitalization and used Poisson regression to assess temporal trends in fall incidence and hospital admissions. Results: An estimated average of 320,751 bed-related fall injuries presented to EDs annually from 2014 to 2023. ED visits increased by 2.85% per year, while hospital admissions rose by 5.67% per year (p < 0.001). The most common injury patterns were superficial injuries (contusions, abrasions, lacerations, avulsions, and punctures) (28.6%), fractures (21.7%), and internal injuries (including concussions) (21.6%). Most of the falls occurred while transitioning into or out of bed (34.4%) or falling out of bed (56.8%). Hospitalization was required in 34.1% of cases and was associated with male sex, medication use at time of injury, and fracture injuries. Conclusions: Bed-related falls and associated hospitalizations are increasing among older adults. ED providers should understand risk factors for hospitalization in these common injuries such as male sex, medication use at time of injury, and high-risk injury patterns. Additionally, prevention efforts should focus on helping older adults remain safely in bed and then assisting with transitions into or out of bed.

Abstract Aggregation and nuclear depletion of the RNA binding protein TDP-43 are the crucial pathological features of amyotrophic lateral sclerosis (ALS) and inclusion body myositis (IBM), two degenerative diseases of the CNS and muscle. The loss of TDP-43 nuclear function results in the aberrant inclusion of cryptic exons in mRNA transcripts, leading to the expression of de novo proteins. Clonally expanded and highly differentiated CD8 + T cells have been observed in individuals with TDP-43 proteinopathies and therapeutics modulating the T cell response have recently been found to extend survival. However, the target antigens mediating T cell activation have remained elusive. Here, we investigate whether the de novo proteins induced by aberrant cryptic splicing due to TDP-43 nuclear loss can act as neo-antigens. We detect the HDGFL2 cryptic peptide and multiple other TDP-43 cryptic exons in IBM skeletal muscle, where their presence correlates with enrichment of T cells and class I antigen presentation pathways. Furthermore, we identify epitopes deriving from HDGFL2 and IGLON5 cryptic peptides which are recognized by clonally expanded and functionally differentiated populations of CD8 + T cells in ALS and IBM Patients. Finally, we demonstrate that T cells engineered to express the identified TCRs can bind and activate in response to the cryptic peptide derived epitopes (cryptic epitopes) and are able to kill TDP-43 deficient astrocytes. This work identifies for the first time specific T cell antigens in ALS and IBM, directly linking adaptive immune response to TDP-43 pathology.

Study Design: Single-center retrospective cohort study. Objective: To determine if the 4-rod construct (4RC) is protective against the occurrence of rod fractures when compared with the 3-rod construct (3RC) in adult spinal deformity (ASD) patients with long fusions to the sacrum. Summary of Background Data: Past studies have explored the different outcomes in subjects with dual-rod versus multirod constructs. There is a lack of literature distinguishing the ramifications of 3RC versus 4RC, particularly in the prevalence of rod fractures and rod fractures requiring subsequent revision surgery as a result of pseudarthrosis. Methods: ASD patients undergoing long instrumented fusions to the sacrum were dichotomized between the 3RC and 4RC cohorts. Outcomes of interest include the occurrence of rod fractures (RFs) and RFs requiring revision (RFR). Two-tailed independent-sample t test with Welch's correction and χ 2 /Fisher exact test were used for continuous and categorical variables, respectively. Multivariable logistic regression analysis was performed to assess whether the 4RC is protective against rod fractures when compared with the 3RC. Results: One hundred forty-five patients with a minimum 2-year follow-up were included (3RC=57, 4RC=88). Four RC had a greater body mass index (BMI) ( P =0.002), longer operating room (OR) time ( P =0.002), greater estimated blood loss (EBL) ( P =0.002), total instrumented levels (TIL) ( P =0.028), and more 3-column osteotomies (3COs) performed ( P =0.028). Four RC had greater baseline coronal vertical axis (CVA) (28.2±24.9 vs. 18.5±16.9 mm, P =0.006) and sagittal vertical axis (SVA) (55.1±64.8 vs. 30.4±41.8 mm, P =0.006). Three RC had a greater rate of RF (28.1% vs. 14.8%, P =0.0506) and RFR (14.9% vs. 10.2%, P =0.486) when compared with 4RC, but these findings were not statistically significant. After controlling for BMI, the use of 3-column osteotomies, total instrumented levels, change in coronal alignment (∆CVA), change in sagittal alignment (∆SVA), use of bone morphogenetic protein, and number of interbody fusions, 3RC was associated with 4.93× greater odds of experiencing RFs ( P =0.0078). However, significance fell short when adjusting for the occurrence of RFR [OR=2.58 (0.60–11.19), P =0.2067]. Conclusion: ASD patients having long fusions to the sacrum with 4RC across the lumbosacral junction are shown to be at lesser risk of developing rod fractures but not revision surgery as compared with 3RC at 2-year follow-up.

Abstract Objectives In 2023, AMIA’s Inclusive Language and Context Style Guidelines (the “Guidelines”) were approved by the Board of Directors and made a publicly available resource. This work began in 2021 through AMIA’s DEI Task Force and subsequent DEI Committee; many members provided input, feedback, and time to create the Guidelines. In this paper, the authors provide a transparent account of the origin, development, contents, and dissemination of the Guidelines and share plans for their future development and use. Materials and Methods Our approach to drafting, refining, and distributing the Guidelines included consulting existing language guides, AMIA member reviews, external expert reviews, webinars, and workshops. Through an iterative approach to drafting and refining the Guidelines, the authors consulted relevant language guidelines and many experts throughout and beyond the AMIA community. Results The Inclusive Language Context Guidelines were formally approved by the AMIA Board of Directors on February 15, 2023. The Guidelines included four principles to be considered in scientific communications: Plurality, Precision, Transparency, and Destigmatization. Discussion A moment of vulnerability where an AMIA member raised concerns about the use of harmful language during a presentation resulted in the creation of a principled approach to support inclusive language within biomedical and health informatics communications. We envision that the Guidelines will support health equity by challenging dominant public narratives around health, fostering stronger interdisciplinary collaboration and critical thinking about the impact of language, and creating a more welcoming environment for the broader AMIA community. This work could not have been completed without the support of many AMIA members and other researchers in biomedical and health informatics. The Guidelines are a living document that will continue to be updated with input and feedback from the AMIA community into the future.

Importance Tau positron emission tomography (PET) allows in vivo detection of neurofibrillary tangles, a core neuropathologic feature of Alzheimer disease (AD). Objective To provide estimates of the frequency of tau PET positivity and its associated risk of clinical outcomes. Design, Setting, and Participants Longitudinal study using data pooled from 21 cohorts, comprising a convenience sample of 6514 participants from 13 countries, collected between January 2013 and June 2024. Cognitively unimpaired individuals and patients with a clinical diagnosis of mild cognitive impairment (MCI), AD dementia, or other neurodegenerative disorders were included. Exposures Tau PET with flortaucipir F 18, amyloid-β (Aβ) PET, and clinical examinations. Tau PET scans were visually rated as positive according to a US Food and Drug Administration– and European Medicines Agency–approved method, designed to indicate the presence of advanced neurofibrillary tangle pathology (Braak stages V-VI). Main Outcomes and Measures Frequency of tau PET positivity and absolute risk of clinical progression (eg, progression to MCI or dementia). Results Among the 6514 participants (mean age, 69.5 years; 50.5% female), median follow-up time ranged from 1.5 to 4.0 years. Of 3487 cognitively unimpaired participants, 349 (9.8%) were tau PET positive; the estimated frequency of tau PET positivity was less than 1% in those aged younger than 50 years, and increased from 3% (95% CI, 2%-4%) at 60 years to 19% (95% CI, 16%-24%) at 90 years. Tau PET positivity frequency estimates increased across MCI and AD dementia clinical diagnoses (43% [95% CI, 41%-46%] and 79% [95% CI, 77%-82%] at 75 years, respectively). Most tau PET–positive individuals (92%) were also Aβ PET positive. Cognitively unimpaired participants who were positive for both Aβ PET and tau PET had a higher absolute risk of progression to MCI or dementia over the following 5 years (57% [95% CI, 45%-71%]) compared with both Aβ PET–positive/tau PET–negative (17% [95% CI, 13%-22%]) and Aβ PET–negative/tau PET–negative (6% [95% CI, 5%-8%]) individuals. Among participants with MCI at the time of the tau PET scan, an Aβ PET–positive/tau PET–positive profile was associated with a 5-year absolute risk of progression to dementia of 70% (95% CI, 59%-81%). Conclusions and Relevance In a large convenience sample, a positive tau PET scan occurred at a nonnegligible rate among cognitively unimpaired individuals, and the combination of Aβ PET positivity and tau PET positivity was associated with a high risk of clinical progression in both preclinical and symptomatic stages of AD. These findings underscore the potential of tau PET as a biomarker for staging AD pathology.

Abstract Purpose Lattice radiation therapy (LRT) is a form of spatially fractionated radiation therapy that allows increased total dose delivery aiming for improved treatment response without an increase in toxicities, commonly utilized for palliation of bulky tumors. The LRT treatment planning process is complex, while eligible patients often have an urgent need for expedited treatment start. In this study, we aimed to develop a simulation‐free workflow for volumetric modulated arc therapy (VMAT)‐based LRT planning via deep learning‐predicted synthetic CT (sCT) to expedite treatment initiation. Methods Two deep learning models were initially trained using 3D U‐Net architecture to generate sCT from diagnostic CTs (dCT) of the thoracic and abdomen regions using a training dataset of 50 patients. The models were then tested on an independent dataset of 15 patients using image similarity analysis assessing mean absolute error (MAE) and structural similarity index measure (SSIM) as metrics. VMAT‐based LRT plans were generated based on sCT and recalculated on the planning CT (pCT) for dosimetric accuracy comparison. Differences in dose volume histogram (DVH) metrics between pCT and sCT plans were assessed using the Wilcoxon signed‐rank test. Results The final sCT prediction model demonstrated high image similarity to pCT, with a MAE and SSIM of 38.93 ± 14.79 Hounsfield Units (HU) and 0.92 ± 0.05 for the thoracic region, and 73.60 ± 22.90 HU and 0.90 ± 0.03 for the abdominal region, respectively. There were no statistically significant differences between sCT and pCT plans in terms of organ‐at‐risk and target volume DVH parameters, including maximum dose (Dmax), mean dose (Dmean), dose delivered to 90% (D90%) and 50% (D50%) of target volume, except for minimum dose (Dmin) and (D10%). Conclusion With demonstrated high image similarity and adequate dose agreement between sCT and pCT, our study is a proof‐of‐concept for using deep learning predicted sCT for a simulation‐free treatment planning workflow for VMAT‐based LRT.