COVID-19 Vaccine Information and Infertility Posts on X: Insights on a Misinformation Pandemic.

OBJECTIVE: This study aimed to evaluate misinformation surrounding infertility and the COVID-19 vaccine on X (formerly known as Twitter) by analyzing the prevalence and content of this misinformation across a sample of posts on X. METHODS: This study is a retrospective review of posts on X (formerly known as tweets) from the COVID-19-TweetIDs dataset from July 2021 and November 2021. Included posts were from crucial time points in the COVID-19 vaccine discourse and contained at least one word related to COVID-19 vaccination and fertility. Posts were analyzed and categorized based on factuality, common words, and hashtags. Descriptive statistics on total followers, account verification status, and engagement were obtained. Differences between posts on X classified as factual and misinformation were examined using analysis of variance or χ2 tests. Sentiment analysis determined if post content was generally positive, neutral, or negative. RESULTS: A total of 17,418 relevant posts on X were reviewed: 11,436 from timeframe 1 (July 2021) and 5982 from timeframe 2 (December 2021). Misinformation posts rose from 29.9% in July 2021 to 45.1% in November 2021. In both timeframes, accounts sharing factual information had more followers (p < 0.001), and verified users were more likely to share accurate posts (p ≤ 0.001). Factual and misinformation posts had similar engagement. Sentiment analysis identified that real posts were more positive and misinformation posts were more negative (p < 0.001). CONCLUSIONS AND RELEVANCE: Misinformation about the COVID-19 vaccine and fertility is highly prevalent on X and threatens vaccine uptake in patients desiring future fertility. Accounts sharing factual information were likely to have more followers and be verified; therefore, verifying more physicians sharing accurate information is critical.

An External Validation Study for Automated Segmentation of Vestibular Schwannoma.

OBJECTIVE: To validate how an automated model for vestibular schwannoma (VS) segmentation developed on an external homogeneous dataset performs when applied to internal heterogeneous data. PATIENTS: The external dataset comprised 242 patients with previously untreated, sporadic unilateral VS undergoing Gamma Knife radiosurgery, with homogeneous magnetic resonance imaging (MRI) scans. The internal dataset comprised 10 patients from our institution, with heterogeneous MRI scans. INTERVENTIONS: An automated VS segmentation model was developed on the external dataset. The model was tested on the internal dataset. MAIN OUTCOME MEASURE: Dice score, which measures agreement between ground truth and predicted segmentations. RESULTS: When applied to the internal patient scans, the automated model achieved a mean Dice score of 61% across all 10 images. There were three tumors that were not detected. These tumors were 0.01 ml on average (SD = 0.00 ml). The mean Dice score for the seven tumors that were detected was 87% (SD = 14%). There was one outlier with Dice of 55%-on further review of this scan, it was discovered that hyperintense petrous bone had been included in the tumor segmentation. CONCLUSIONS: We show that an automated segmentation model developed using a restrictive set of siloed institutional data can be successfully adapted for data from different imaging systems and patient populations. This is an important step toward the validation of automated VS segmentation. However, there are significant shortcomings that likely reflect limitations of the data used to train the model. Further validation is needed to make automated segmentation for VS generalizable.

Surgical Considerations in Inner Ear Gene Therapy from Human Temporal Bone Anatomy.

OBJECTIVE(S): Recently directed methods of inner ear drug delivery underscore the necessity for understanding critical anatomical dimensions. This study examines anatomical measurements of the human middle and inner ear relevant for inner ear drug delivery studied with three different imaging modalities. METHODS: Post-mortem human temporal bones were analyzed using human temporal bone histopathology (N = 24), micro computerized tomography (µCT; N = 4), and synchrotron radiation phase-contrast imaging (SR-PCI; N = 7). Nine measurements involving the oval and round windows were performed when relevant anatomical structures were visualized for subsequent age-controlled analysis, and comparisons were made between imaging methods. RESULTS: Combined human temporal bone histopathology showed the mean distance to the saccule from the center of the stapes footplate (FP) was 2.07 ± 0.357 mm and the minimum distance was 1.23 mm. The mean distance from the round window membrane (RWM) to the osseous spiral lamina (OSL) was 1.75 ± 0.199 mm and the minimum distance was 1.43 mm. Instruments inserted up to 1 mm past the center of the FP are unlikely to cause saccular damage, provided there are no endolymphatic hydrops. Similarly, instruments inserted up to 1 mm through the RWM in the trajectory toward the OSL are unlikely to cause OSL damage. CONCLUSION: The combined analyses of inner-ear dimensions of age-controlled groups and imaging modalities demonstrate critical dimensions of importance to consider when inserting delivery vehicles into the human cochlea. LEVEL OF EVIDENCE: N/A Laryngoscope, 134:2879-2888, 2024.

Evaluating the Feasibility of a Novel Firearm Injury Prevention Program for Pre-adolescent Children Through Health Care and Community-Based Partnerships: The Future Healers Program Pilot Study.

BACKGROUND: Firearm violence is an American public health crisis that negatively impacts children and disproportionately affects Black youth. Few firearm injury prevention programs have been described in pre-adolescent children. The Future Healers Program is a novel collaboration constructed via partnership between the medical school, trauma center, academic surgery department, and local non-profit community organization. Our study sought to evaluate if (1) partnering with community organizations facilitated recruitment of children with prior exposure to firearm violence and (2) the health care community was a potential trusted partner appropriate for program delivery. METHODS: Children aged 4-13 were recruited to join the program via news outlets and social media and in partnership with a local non-profit organization. Of the children and parents participating in the program, 48% (44/92) and 59% (38/64), respectively, completed an IRB-approved survey study. Pearson's chi-square, percentages, and 95% confidence intervals evaluated differences between children and caregivers on sociodemographic characteristics, firearm exposure (FE), firearm violence exposure (FVE), and perception of health care. Participant's residence was geocoded in relationship to incidents of firearm injury (2008-2021) in the same region. RESULTS: Caregivers (95%) and children (84%) reported substantial exposure to firearm violence and resided in areas with frequent firearm injury incidents. Notably, 82% of caregivers and 66% of children reported having a family member injured by gunfire. A high percentage of caregivers (79%) and children (91%) self-reported trust in the health care system. CONCLUSION: Partnerships between community organizations and health care systems can develop prevention programs that effectively recruit and engage pre-adolescent children impacted by firearm violence.

Sarcopenia of the longitudinal tongue muscles in rats.

The tongue is a muscular hydrostat, with lingual movements occurring during breathing, chewing, swallowing, vocalization, vomiting, coughing and grooming/sexual activities. In the elderly, reduced lingual dysfunction and weakness contribute to increased risks of obstructive sleep apnea and aspiration pneumonia. In Fischer 344 (F344) rats, a validated model of aging, hypoglossal motor neuron death is apparent, although there is no information regarding tongue strength. The intrinsic tongue muscles, the superior and inferior longitudinal, transversalis and verticalis exist in an interdigitated state. Recently, we established a method to measure the specific force of individual intrinsic tongue muscle, accounting for the tissue bulk that is not in the direction of uniaxial force. In the longitudinal muscles of 6- (n = 10), 18- (n = 9) and 24-month-old (n = 12) female and male F344 rats, we assessed specific force, fatigability, fiber type dependent cross-sectional area (CSA) and overall CSA. Muscle force and fatigue was assessed ex vivo using platinum plate simulation electrodes. Tongue muscles were frozen in melting isopentane, and transverse sections cut at 10 µm. Muscle fiber type was classified based on immunoreactivity to myosin heavy chain (MyHC) isoform antibodies. In H&E stained muscle, CSA and uniaxial muscle contributions to total tongue bulk was assessed. We observed a robust ∼30% loss of longitudinal specific force, with reductions in overall longitudinal muscle fiber CSA and specific atrophy of type IIx/IIb fibers. It will be important to investigate the mechanistic underpinnings of hypoglossal motor neuron death and tongue muscle weakness to eventually provide therapies for age-associated lingual dysfunctions.

Barriers to Family Building Among Physicians and Medical Students.

Importance: Physicians and medical students who desire to build families face significant barriers due to the structure and culture of medicine. Objective: To understand the barriers and facilitators to family building for all people in medicine-not only individuals who can become pregnant-through an open-ended, qualitative analysis of survey responses. Design, Setting, and Participants: This qualitative study used a survey conducted in April and May 2021 with a broad sample of physicians and medical students. Participants were recruited through social media, targeting physician and medical student communities. Physicians (residents, fellows, and physicians in independent practice) and medical students of all gender identities and sexual orientations were included. Informed by a postpositivist approach, coding reliability thematic analysis was performed on 3 open-ended survey questions on family-building experiences (what they would do differently, what advice they have for others, and anything else they wished to share). Main Outcomes and Measures: Identified themes were mapped to the social-ecological model, a model used in public health to examine how a spectrum of factors is associated with health outcomes. Results: A total of 2025 people (1860 [92%] women; 299 [15%] Asian, 151 [8%] Black, and 1303 [64%] White; 1730 [85%] heterosexual; and 1200 [59%] physicians who had completed training) responded to at least 1 of 3 open-ended questions. Themes mapped to social-ecological model levels included: (1) cultural, eg, medical training being at odds with family building; (2) organizational, eg, lack of institutional support for the range of family-building routes; (3) interpersonal, eg, impact of social support on family building; and (4) individual, eg, socioeconomic status and other individual factors that facilitate or inhibit family building. Recommendations to improve family-building experiences include implementing family-building curricula at medical schools, providing adequate parental leave for all physicians and medical students who become parents, and providing insurance coverage for all family-building routes. Conclusions and Relevance: In this qualitative study of physicians and medical students, self-reported barriers to family building were identified at each level of the social-ecological model. Addressing these barriers is critical to creating a more equitable family-building environment for physicians and medical students.

Identification of immune-related candidate biomarkers in plasma of patients with sporadic vestibular schwannoma.

Vestibular schwannoma (VS) is an intracranial tumor arising from neoplastic Schwann cells and typically presenting with hearing loss. The traditional belief that hearing deficit is caused by physical expansion of the VS, compressing the auditory nerve, does not explain the common clinical finding that patients with small tumors can have profound hearing loss, suggesting that tumor-secreted factors could influence hearing ability in VS patients. We conducted profiling of patients' plasma for 66 immune-related factors in patients with sporadic VS (N > 170) and identified and validated candidate biomarkers associated with tumor size (S100B) and hearing (MCP-3). We further identified a nine-biomarker panel (TNR-R2, MIF, CD30, MCP-3, IL-2R, BLC, TWEAK, eotaxin, and S100B) with outstanding discriminatory ability for VS. These findings revealed possible therapeutic targets for VS, providing a unique diagnostic tool that may predict hearing change and tumor growth in VS patients, and may inform the timing of tumor resection to preserve hearing.

Carrageenan-Based Crowding and Confinement Combination Approach to Increase Collagen Deposition for In Vitro Tissue Development.

Connective tissue models grown from cell monolayers can be instrumental in a variety of biomedical fields such as drug screening, wound healing, and regenerative engineering. However, while connective tissues contain abundant fibrillar collagen, achieving a sufficient assembly and retention of fibrillar collagen in vitro is challenging. Unlike the dilute cell culture environment, the body's environment is characterized by a high density of soluble macromolecules (crowding) and macromolecular networks (confinement), which contribute to extracellular matrix (ECM) assembly in vivo. Consequently, macromolecular crowding (MMC) has been successfully used to enhance the processing of type I procollagen, leading to significant increases in fibrillar collagen assembly and accumulation during in vitro culture of a variety of cell types. In this study, we developed a combination approach using a carrageenan hydrogel, which released soluble macromolecules and served as a confinement barrier. We first evaluated the local carrageenan release and then confirmed the effectiveness of this combination approach on collagen accumulation by the human MG-63 bone cell line. Additionally, computational modeling of oxygen and glucose transport within the culture system showed no negative effects of the hydrogel and its releasates on cell viability.

Psychosocial Burdens Associated With Family Building Among Physicians and Medical Students.

This survey study uses responses from physicians and medical students to assess psychosocial burdens of family building in the physician workforce.

Money can't buy happiness: A randomized controlled trial of a digital mental health app with versus without financial incentives.

Mental health disorders are prevalent among college students and increasing in frequency and severity. However, there is a significant gap between those who need treatment and those who engage in treatment. Given the documented efficacy of financial incentives for promoting health behavior change and engagement in treatment, financial incentives may help, along with nonfinancial behavioral incentives such as motivational messaging, gamification, and loss aversion techniques. We compared brief (28-day) use of two versions of a behavioral economics-inspired digital mental health app, NeuroFlow: (1) the full app including financial incentives and nonfinancial behavioral incentives (treatment group) and (2) a version of the app with nonfinancial behavioral incentives only (control group). In our intent-to-treat analyses, in order to examine the primary outcome of app engagement, a one-way analysis of variance (ANOVA) (treatment vs. control) was conducted, and to examine the secondary outcomes (depression, anxiety, emotion dysregulation, and wellbeing), a two-way repeated measures ANOVAs (treatment vs. control × baseline vs. post-trial) were conducted. We found that there were no differences between treatment groups on app engagement or the change in the mental health/wellness outcome measures. There was a main effect of timepoint on symptoms of anxiety and emotion dysregulation, such that there were significantly lower self-reported symptoms at post-trial relative to baseline. Our results suggest that financial incentives in digital mental health apps over and above nonfinancial behavioral incentives do not have an impact on app engagement or mental health/wellness outcomes.

A Digital Mental Health App Incorporating Wearable Biosensing for Teachers of Children on the Autism Spectrum to Support Emotion Regulation: Protocol for a Pilot Randomized Controlled Trial.

BACKGROUND: As much as 80% of children on the autism spectrum exhibit challenging behaviors (ie, behaviors dangerous to the self or others, behaviors that interfere with learning and development, and behaviors that interfere with socialization) that can have a devastating impact on personal and family well-being, contribute to teacher burnout, and even require hospitalization. Evidence-based practices to reduce these behaviors emphasize identifying triggers (events or antecedents that lead to challenging behaviors); however, parents and teachers often report that challenging behaviors surface with little warning. Exciting recent advances in biometric sensing and mobile computing technology allow the measurement of momentary emotion dysregulation using physiological indexes. OBJECTIVE: We present the framework and protocol for a pilot trial that will test a mobile digital mental health app, the KeepCalm app. School-based approaches to managing challenging behaviors in children on the autism spectrum are limited by 3 key factors: children on the autism spectrum often have difficulties in communicating their emotions; it is challenging to implement evidence-based, personalized strategies for individual children in group settings; and it is difficult for teachers to track which strategies are successful for each child. KeepCalm aims to address those barriers by communicating children's stress to their teachers using physiological signaling (emotion dysregulation detection), supporting the implementation of emotion regulation strategies via smartphone pop-up notifications of top strategies for each child according to their behavior (emotion regulation strategy implementation), and easing the task of tracking outcomes by providing the child's educational team with a tool to track the most effective emotion regulation strategies for that child based on physiological stress reduction data (emotion regulation strategy evaluation). METHODS: We will test KeepCalm with 20 educational teams of students on the autism spectrum with challenging behaviors (no exclusion based on IQ or speaking ability) in a pilot randomized waitlist-controlled field trial over a 3-month period. We will examine the usability, acceptability, feasibility, and appropriateness of KeepCalm as primary outcomes. Secondary preliminary efficacy outcomes include clinical decision support success, false positives or false negatives of stress alerts, and the reduction of challenging behaviors and emotion dysregulation. We will also examine technical outcomes, including the number of artifacts and the proportion of time children are engaged in high physical movement based on accelerometry data; test the feasibility of our recruitment strategies; and test the response rate and sensitivity to change of our measures, in preparation for a future fully powered large-scale randomized controlled trial. RESULTS: The pilot trial will begin by September 2023. CONCLUSIONS: Results will provide key data about important aspects of implementing KeepCalm in preschools and elementary schools and will provide preliminary data about its efficacy to reduce challenging behaviors and support emotion regulation in children on the autism spectrum. TRIAL REGISTRATION: ClinicalTrials.gov NCT05277194; https://www.clinicaltrials.gov/ct2/show/NCT05277194. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/45852.

Perceptions of General Surgery Program Leadership and Residents on Research Sabbatical.

INTRODUCTION: The incorporation of a 1-y- or 2-y research period during general surgery residency is increasingly common in many academic programs, yet often, it is heterogeneously structured and ill-defined. This survey-based observational study aimed to characterize the perceptions of general surgery program directors (PDs) and residents regarding an in-training, dedicated research sabbatical. METHODS: Two surveys were conducted using Qualtrics software. One survey was sent to general surgery residency PDs, and the other was sent to general surgery residents currently on a research sabbatical. The primary aim of the survey was to assess the PDs' and research residents' perceptions of the research sabbatical. RESULTS: Seven hundred and fifty-two surveys were analyzed, of which 120 were from PDs and 632 from research residents. Among the residents, 44.1% felt that the research time delayed their surgical training. Regarding research funding, 46.7% of the responding residents said that their residency program funded their research, 30.9% said they acquired funding independently, and 19.1% said that it came from a combination of residency program and independent funding. Finally, regarding how residents found their research opportunity, 42.7% said they found it independently and 53.3% said their program provided it. CONCLUSIONS: Research sabbaticals during residency may be considered essential to academic development. However, in this survey-based study, perceptions of research time and its structure varied greatly between PDs and residents. An intentional push toward developing guidelines for research sabbaticals may benefit residency program leadership and residents.

Immune cells are increased in normal breast tissues of BRCA1/2 mutation carriers.

PURPOSE: Breast cancer risk is elevated in pathogenic germline BRCA 1/2 mutation carriers due to compromised DNA quality control. We hypothesized that if immunosurveillance promotes tumor suppression, then normal/benign breast lobules from BRCA carriers may demonstrate higher immune cell densities. METHODS: We assessed immune cell composition in normal/benign breast lobules from age-matched women with progressively increased breast cancer risk, including (1) low risk: 19 women who donated normal breast tissue to the Komen Tissue Bank (KTB) at Indiana University Simon Cancer Center, (2) intermediate risk: 15 women with biopsy-identified benign breast disease (BBD), and (3) high risk: 19 prophylactic mastectomies from women with germline mutations in BRCA1/2 genes. We performed immunohistochemical stains and analysis to quantitate immune cell densities from digital images in up to 10 representative lobules per sample. Median cell counts per mm2 were compared between groups using Wilcoxon rank-sum tests. RESULTS: Normal/benign breast lobules from BRCA carriers had significantly higher densities of immune cells/mm2 compared to KTB normal donors (all p < 0.001): CD8 + 354.4 vs 150.9; CD4 + 116.3 vs 17.7; CD68 + 237.5 vs 57.8; and CD11c + (3.5% vs 0.4% pixels positive). BBD tissues differed from BRCA carriers only in CD8 + cells but had higher densities of CD4 + , CD11c + , and CD68 + immune cells compared to KTB donors. CONCLUSIONS: These preliminary analyses show that normal/benign breast lobules of BRCA mutation carriers contain increased immune cells compared with normal donor breast tissues, and BBD tissues appear overall more similar to BRCA carriers.

New hyaluronan-based biomatrix for 3-D follicle culture yields functionally competent oocytes.

BACKGROUND: Encapsulation of follicles within a biomatrix is one approach to maintaining 3-D follicle architecture during culture. Hyaluronan is one component of the natural extracellular matrix (ECM) that provides support to cells in vivo. This report describes the application of a novel tyramine-linked hyaluronan for 3-D in vitro follicle culture and the production of developmentally competent metaphase II oocytes. MATERIALS AND METHODS: Enzymatically isolated mouse preantral follicles or follicle clusters (FL-C) from fresh or vitrified ovaries were encapsulated in 3 mg/ml of hyaluronan gel (HA). Follicle growth, antrum formation and meiotic maturation to metaphase II oocytes was monitored. Chromatin staining was used to assess GV oocyte progression towards meiotic competence. Functional competence of in vitro matured (IVM) oocytes was evaluated by in vitro fertilization and ability to develop to blastocyst. Modifying the HA gel by inclusion of laminin (HA-LM), mouse sarcoma extracellular matrix (Matrigel;HA-MG) or placental extracellular matrix (HA-PM) was also tested to see if this might further enhance IVM outcomes. RESULTS: A total of 402 preantral follicles were cultured in HA gel. After hCG trigger, 314 oocyte-cumulus complexes ovulated from the embedded follicles. Meiotic maturation rate to the metaphase II stage was 73% (228/314). After insemination 83% (188/228) of IVM oocytes fertilized with a subsequent blastulation rate of 46% (87/188). A pilot transfer study with 3 recipient mice resulted in the birth of a single pup. HA gel supported individually isolated follicles as well ovarian tissue fragments containing clusters of 6-8 preantral follicles. Meiotic maturation was lower with FL-clusters from vitrified versus fresh ovaries (34% and 55%, respectively; p < 0.007). Modification of the HA gel with ECMs or laminin affected antrum formation and follicle retention. Maturation rates to the metaphase II stage were however not significantly different: 74% for HA gel alone as compared to HA-LM (67%), HA-MG (56%) and HA-PM (58%). CONCLUSION: Hyaluronan gel is an effective and versatile extracellular matrix based biomaterial for 3-D culture of ovarian follicles. This culture model allowed ovulation of functionally competent metaphase II oocytes, capable of fertilization, genomic activation and blastulation. Future testing with human follicles that require longer in vitro culture times should be considered.

Reversible contrast enhancement for visualization of human temporal bones using micro computed tomography.

Sensorineural hearing loss (SNHL), which typically arises from the inner ear, is the most common sensory deficit worldwide. The traditional method for studying pathophysiology underlying human SNHL involves histological processing of the inner ear from temporal bones collected during autopsy. Histopathological analysis is destructive and limits future use of a given specimen. Non-destructive strategies for the study of the inner ear are urgently needed to fully leverage the utility of each specimen because access to human temporal bones is increasingly difficult and these precious specimens are required to uncover disease mechanisms and to enable development of new devices. We highlight the potential of reversible iodine staining for micro-computed tomography imaging of the human inner ear. This approach provides reversible, high-resolution visualization of intracochlear structures and is becoming more rapid and accessible.

Structure and Function of the Mammalian Neuromuscular Junction.

The mammalian neuromuscular junction (NMJ) comprises a presynaptic terminal, a postsynaptic receptor region on the muscle fiber (endplate), and the perisynaptic (terminal) Schwann cell. As with any synapse, the purpose of the NMJ is to transmit signals from the nervous system to muscle fibers. This neural control of muscle fibers is organized as motor units, which display distinct structural and functional phenotypes including differences in pre- and postsynaptic elements of NMJs. Motor units vary considerably in the frequency of their activation (both motor neuron discharge rate and duration/duty cycle), force generation, and susceptibility to fatigue. For earlier and more frequently recruited motor units, the structure and function of the activated NMJs must have high fidelity to ensure consistent activation and continued contractile response to sustain vital motor behaviors (e.g., breathing and postural balance). Similarly, for higher force less frequent behaviors (e.g., coughing and jumping), the structure and function of recruited NMJs must ensure short-term reliable activation but not activation sustained for a prolonged period in which fatigue may occur. The NMJ is highly plastic, changing structurally and functionally throughout the life span from embryonic development to old age. The NMJ also changes under pathological conditions including acute and chronic disease. Such neuroplasticity often varies across motor unit types. © 2022 American Physiological Society. Compr Physiol 12:1-36, 2022.

Association Between Implementation of a Geriatric Trauma Clinical Pathway and Changes in Rates of Delirium in Older Adults With Traumatic Injury.

Importance: Older adults (age ≥65 years) are at risk for high rates of delirium and poor outcomes; however, how to improve outcomes is still being explored. Objective: To assess whether implementation of a geriatric trauma clinical pathway was associated with reduced rates of delirium in older adults with traumatic injury. Design, Setting, and Participants: A retrospective case-control study of electronic health records of patients aged 65 years or older with traumatic injury from 2018 to 2020 was conducted at a single level I trauma center. Eligible patients were age 65 years or older admitted to the trauma service and who did not undergo an operation. Intervention: The implementation of a clinical pathway based on geriatric best practices, which included order sets, guidelines, automated consultations, and escalation pathways executed by a multidisciplinary team. Main Outcomes and Measures: The primary outcome was delirium. The secondary outcome was hospital length of stay. Process measures for pathway compliance were also assessed. Results: Of the 859 eligible patients, 712 patients were included in the analysis (442 [62.1%] in the baseline group; 270 [37.9%] in the postimplementation group; mean [SD] age: 81.4 [9.1] years; 394 [55.3%] were female). The mechanism of injury was not different between groups, with 247 in the baseline group (55.9%) and 162 in the postimplementation group (60.0%) (P = .43) experiencing a fall. Injuries were minor or moderate in both groups (261 in baseline group [59.0%] and 168 in postimplementation group [62.2%]; P = .87). The adjusted odds ratio for delirium in the postimplementation cohort was 0.54 (95% CI, 0.37-0.80; P < .001). Goals of care documentation improved significantly in the postimplementation cohort vs the baseline cohort with regard to documented goals of care notes (53.7% in the postimplementation cohort [145 of 270] vs 16.7% in the baseline cohort [74 of 442]; P < .001) and a shortened time to discussion from presenting to the emergency department (36 hours in the postimplementation cohort vs 50 hours in the baseline cohort; P = .03). Conclusions and Relevance: In this study, implementation of a multidisciplinary clinical pathway for injured older adults at a single level I trauma center was associated with improved care and clinical outcomes. Interventions such as these may have utility in this vulnerable population, and findings should be confirmed across multiple centers.

Mitochondrial adaptations to inactivity in diaphragm muscle fibers.

Type I and IIa diaphragm muscle (DIAm) fibers comprise slow and fast fatigue-resistant motor units that are recruited to accomplish breathing and thus have a high duty cycle. In contrast, type IIx/IIb fibers comprise more fatigable fast motor units that are infrequently recruited for airway protective and straining behaviors. We hypothesize that mitochondrial structure and function in type I and IIa DIAm fibers adapt in response to inactivity imposed by spinal cord hemisection at C2 (C2SH). At 14 days after C2SH, the effect of inactivity on mitochondrial structure and function was assessed in DIAm fibers. Mitochondria in DIAm fibers were labeled using MitoTracker Green (Thermo Fisher Scientific), imaged in three-dimensions (3-D) by fluorescence confocal microscopy, and images were analyzed for mitochondrial volume density (MVD) and complexity. DIAm homogenate from either side was assessed for PGC1α, Parkin, MFN2, and DRP1 using Western blot. In alternate serial sections of the same DIAm fibers, the maximum velocity of the succinate dehydrogenase reaction (SDHmax) was determined using a quantitative histochemical technique. In all groups and both sides of the DIAm, type I and IIa DIAm fibers exhibited higher MVD, with more filamentous mitochondria and had higher SDHmax normalized to both fiber volume and mitochondrial volume compared with type IIx/IIb Diam fibers. In the inactive right side of the DIAm, mitochondria became fragmented and MVD decreased in all fiber types compared with the intact side and sham controls, consistent with the observed reduction in PGC1α and increased Parkin and DRP1 expression. In the inactive side of the DIAm, the reduction in SDHmax was found only for type I and IIa fibers. These results show that there are intrinsic fiber-type-dependent differences in the structure and function of mitochondria in DIAm fibers. Following C2SH-induced inactivity, mitochondrial structure (MVD and fragmentation) and function (SDHmax) were altered, indicating that inactivity influences all DIAm fiber types, but inactivity disproportionately affected SDHmax in the more intrinsically active type I and IIa fibers.NEW & NOTEWORTHY Two weeks of diaphragm (DIAm) inactivity imposed by C2SH caused reduced mitochondrial volume density, mitochondrial fragmentation, and a concomitant reduction of SDHmax in type I and IIa DIAm fibers on the lesioned side. Type I and IIa DIAm fibers were far more sensitive to inactivation than type IIx/IIb fibers, which exhibited little pathology. Our results indicate that mitochondria in DIAm fibers are plastic in response to varying levels of activity.

Sporadic Vestibular Schwannoma Size and Location Do not Correlate With the Severity of Hearing Loss at Initial Presentation.

Vestibular schwannoma (VS) is a non-malignant intracranial neoplasm arising from the vestibular branch of the 8th cranial nerve; sensorineural hearing loss (SNHL) is the most common associated symptom. Understanding whether VS imaging characteristics at the time of VS diagnosis can be associated with severity of VS-induced SNHL can impact patient counseling and define promising areas for future research. Patients diagnosed with VS at Massachusetts Eye and Ear (MEE) from 1994 through 2018 were analyzed if magnetic resonance imaging at VS presentation and sequential audiometry were available. Results were compared with original studies available in PubMed, written in English, on VS imaging characteristics and their impact on hearing in patients. A total of 477 patients with unilateral VS from the MEE database demonstrated no significant correlation between any features of tumor imaging at the time of VS diagnosis, such as VS size, impaction or location, and any hearing loss metric. Twenty-three published studies on the impact of VS imaging characteristics on patient hearing met inclusion criteria, with six solely involving NF2 patients and three including both sporadic and NF2-related VS patients. Fifteen studies reported a significant relationship between SNHL and at least one VS imaging characteristic; however, these trends were universally limited to NF2 patients or involved small patient populations, and were not reproduced in larger studies. Taken together, SNHL in sporadic VS patients is not readily associated solely with any tumor imaging characteristics. This finding motivates future studies to define how VS microenvironment and secreted molecules influence VS-induced SNHL.