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Background Bruising in an infant is an important sentinel injury that should raise concern for child physical abuse, and should prompt a medical evaluation for occult injury. Hyperflexion during forceful squeezing of an infant's hand results in a distinct pattern of bruising along the palmar and interdigital creases, as well as the palmar eminences. Self-inflicted injury by the infant or injury resulting from benign handling should not be accepted as plausible explanations for this injury. The presence of concurrent occult injuries is common, and further supports concerns for abuse. However, when this distinct pattern of palm bruising is identified in an infant, the absence of occult injuries should not prevent the recognition of child physical abuse. Case Report We report 11 cases depicting this distinct pattern of palm bruising in infants. Additionally, we include a perpetrator's documented confession. To the best of our knowledge, this pattern of bruising has not been previously described in the medical literature. Why Should an Emergency Physician Be Aware of This? Emergency physicians play a crucial role in recognizing and addressing child physical abuse. Prompt recognition of this finding can aid in the identification of child physical abuse, even in the absence of underlying occult injury. This, in turn, can potentially prevent further injury, and even death, of an infant.

Background American Indian/Alaska Native (AI/AN) populations have been disproportionately affected by chronic respiratory diseases for reasons incompletely understood. Past research into disease disparity using population-based surveys mostly focused on state-specific factors. The present study investigates the independent contributions of AI/AN racial status and other socioeconomic/demographic variables to chronic respiratory disease disparity in an 11-state region with historically high AI/AN representation. Using data from the Behavioral Risk Factor Surveillance System (BRFSS) spanning years 2011–2018, this work provides an updated assessment of disease disparity and potential determinants of respiratory health in AI/AN populations. Methods This cross-sectional study used data from the BRFSS survey, 2011–2018. The study population included AI/AN and non-Hispanic white individuals resident in 11 states with increased proportion of AI/AN individuals. The yearly number of respondents averaged 75,029 (62878–87,350) which included approximately 5% AI/AN respondents (4.5–6.3%). We compared the yearly adjusted prevalence for chronic respiratory disease, where disease status was defined by self-reported history of having asthma and/or chronic obstructive pulmonary disease (COPD). Multivariable logistic regression was performed to determine if being AI/AN was independently associated with chronic respiratory disease. Covariates included demographic (age, sex), socioeconomic (marital status, education level, annual household income), and behavioral (smoking, weight morbidity) variables. Results The AI/AN population consistently displayed higher adjusted prevalence of chronic respiratory disease compared to the non-Hispanic white population. However, the AI/AN race/ethnicity characteristic was not independently associated with chronic respiratory disease (OR, 0.93; 95% CI, 0.79–1.10 in 2017). In contrast, indicators of low socioeconomic status such as annual household income of Conclusions This study highlighted that AI/AN socioeconomic burdens are key determinants of chronic respiratory disease, in addition to well-established risk factors such as smoking and weight morbidity. Disease disparity experienced by the AI/AN population is therefore likely a symptom of disproportionate socioeconomic challenges they face. Further promotion of public health and social service efforts may be able to improve AI/AN health and decrease this disease disparity.

Background Literature demonstrates increased mortality for the severely injured at a Level II vs. Level I center. Our objective is to reevaluate the impact of trauma center verification level on mortality for patients with an Injury Severity Score (ISS) > 15 utilizing more contemporary data. We hypothesize that there would be no mortality discrepancy. Study Design Utilizing the ACS Trauma Quality Program Participant Use File admission year 2017, we identified severely injured (ISS >15) adult (age >15 years) patients treated at an ACS-verified Level I or Level II center. We excluded patients who underwent interfacility transfer. Logistic regression was performed to determine adjusted associations with mortality. Results There were 63 518 patients included, where 43 680 (68.8%) were treated at a Level I center and 19 838 (31.2%) at a Level II. Male gender (70.1%) and blunt injuries (92.0%) predominated. Level I admissions had a higher mean ISS [23.8 (±8.5) vs. 22.9 (±7.8), Conclusions Despite previous findings, mortality outcomes are similar for severely injured patients treated at a Level I vs. Level II center. We theorize that this relates to mandated Level II resourcing as defined by an updated American College of Surgeons verification process.

Dockstore (https://dockstore.org/) is an open source platform for publishing, sharing, and finding bioinformatics tools and workflows. The platform has facilitated large-scale biomedical research collaborations by using cloud technologies to increase the Findability, Accessibility, Interoperability and Reusability (FAIR) of computational resources, thereby promoting the reproducibility of complex bioinformatics analyses. Dockstore supports a variety of source repositories, analysis frameworks, and language technologies to provide a seamless publishing platform for authors to create a centralized catalogue of scientific software. The ready-to-use packaging of hundreds of tools and workflows, combined with the implementation of interoperability standards, enables users to launch analyses across multiple environments. Dockstore is widely used, more than twenty-five high-profile organizations share analysis collections through the platform in a variety of workflow languages, including the Broad Institute's GATK best practice and COVID-19 workflows (WDL), nf-core workflows (Nextflow), the Intergalactic Workflow Commission tools (Galaxy), and workflows from Seven Bridges (CWL) to highlight just a few. Here we describe the improvements made over the last four years, including the expansion of system integrations supporting authors, the addition of collaboration features and analysis platform integrations supporting users, and other enhancements that improve the overall scientific reproducibility of Dockstore content., Graphical Abstract Graphical AbstractDockstore: enhancing an open platform for sharing Docker-based tools described with workflow languages for the sciences.

OBJECTIVES: To determine the association of life-space score with subsequent healthcare costs and utilization. DESIGN: Prospective cohort study (Osteoporotic Fracture in Men [MrOS]). SETTING: Six U.S. sites. PARTICIPANTS: A total of 1555 community-dwelling men (mean age 79.3 years; 91.5% white, non-Hispanic) participating in the MrOS Year 7 (Y7) examination linked with their Medicare claims data. MEASUREMENTS: Life-space during the past month was assessed as 0 (daily restriction to one's bedroom) to 120 (daily trips outside one's town without assistance) and categorized (0-40, 41-60, 61-80, 81-100, 101-120). Total annualized direct healthcare costs and utilization were ascertained during 36 months after the Y7 examination. RESULTS: Mean total annualized costs (2020 U.S. dollars) steadily increased across category of life-space score, from $7954 (standard deviation [SD] 16,576) among men with life-space scores of 101-120 to $26,430 (SD 28,433) among men with life-space scores of 0-40 (p < 0.001). After adjustment for demographics, men with a life-space score of 0-40 versus men with a life-space score of 101-120 had greater mean total costs (cost ratio [CR] = 2.52; 95% confidence interval [CI] = 1.84-3.45) and greater risk of subsequent hospitalization (odds ratio [OR] 4.72, 95% CI 2.61-8.53) and skilled nursing facility (SNF) stay (OR 7.32, 95% CI 3.65-14.66). Life-space score was no longer significantly associated with total healthcare costs (CR for 0-40 vs 101-120 1.29; 95% CI 0.91-1.84) and hospitalization (OR 1.76, 95% CI 0.89-3.51) after simultaneous consideration of demographics, medical factors, self-reported health and function, and the frailty phenotype; the association of life-space with SNF stay remained significant (OR 2.86, 95% CI 1.26-6.49). CONCLUSION: Our results highlight the importance of function and mobility in predicting future healthcare costs and suggest the simple and convenient life-space score may in part capture risks from major geriatric domains and improve identification of older, community-dwelling men likely to require costly care.

Terrestrial neutron and alpha particle irradiation data for a 7-nm bulk FinFET technology reveal the persisting reliability threat single-event latchup (SEL) poses to advanced technology nodes. SEL is characterized over a wide range of supply voltages and temperatures for this technology node. SEL data is analyzed to determine the holding voltage ( $V_{\mathrm {HOLD}}$ ) required to sustain SEL, which can be as low as 0.85 V at elevated temperatures. Such low SEL holding voltage within 100 mV of nominal supply voltage poses a major reliability threat.

Clinical staging of accidental hypothermia is used to guide out-of-hospital treatment and transport decisions. Most clinical systems utilize core temperature, by measurement or estimation, to stage hypothermia, despite the challenge of obtaining accurate field measurements. Recent studies have demonstrated that field estimation of core temperature is imprecise. We propose a revision of the original Swiss Staging system. The revised system uses the risk of cardiac arrest, instead of core temperature, to determine the staging level. Our revised system simplifies assessment by using the level of responsiveness, based on the AVPU scale, and by removing shivering as a stage-defining sign.

The coronavirus disease pandemic has highlighted the key role epidemiologic models play in supporting public health decision-making. In particular, these models provide estimates of outbreak potential when data are scarce and decision-making is critical and urgent. We document the integrated modeling response used in the US state of Utah early in the coronavirus disease pandemic, which brought together a diverse set of technical experts and public health and healthcare officials and led to an evidence-based response to the pandemic. We describe how we adapted a standard epidemiologic model; harmonized the outputs across modeling groups; and maintained a constant dialogue with policymakers at multiple levels of government to produce timely, evidence-based, and coordinated public health recommendations and interventions during the first wave of the pandemic. This framework continues to support the state's response to ongoing outbreaks and can be applied in other settings to address unique public health challenges.

Purpose/aims The purpose of this study was to examine the feasibility and acceptability of a nurse-driven catheter removal protocol among nurses in a hospital setting. Design A mixed-methods design was used. A modified version of the Abbreviated Acceptability Rating Profile was used in this study, along with 3 open-ended questions. Methods Staff nurses assigned to care for nonpregnant, cognitively intact adults with a short-term Foley catheter were asked to apply a nurse-driven catheter removal protocol on the enrolled patient every 12 hours. They were asked to complete a modified version of the Abbreviated Acceptability Rating Profile and open-ended questionnaire each time they used the protocol. Results A total of 13 questionnaires were completed (52% completion rate). Nurses reported that the nurse-driven catheter removal protocol was highly acceptable in intensive care units and intermediate care units, but not in medical-surgical units. Nurses felt that the protocol should be effective in preventing catheter-associated urinary tract infection, that they would be willing to use the protocol with their loved ones, and that overall, the protocol was helpful for their patient. However, they did not feel that their patient's risk for catheter-associated urinary tract infection was high enough to warrant using the protocol. Barriers to using the protocol as planned included encrustation, inconvenient times of day, unawareness, and a desire to follow orders and current institutional policies. Conclusion Findings from this study generally support the acceptability of the nurse-driven catheter removal protocol, particularly in higher-acuity units. Recommendations are provided to help clinical nurse specialists support adherence to these protocols.

Multidisciplinary tumor boards (TBs) is an integral part of cancer care. Emerging evidence shows that effective TB implementation is crucial. It remains largely unknown how digital solutions can assist effective TB conduction. This study aimed to evaluate the impact of a digital solution on case discussion during TB meetings in four cancer types: Breast, Gastrointestinal (GI), Ear, Nose & Throat (ENT), and Hematopathology. A prospective study was performed to evaluate case discussion time during TB meetings pre- and post-solution implementation, at an US academic healthcare cancer center. Data were recorded by a Nurse Navigator for each case during TB meetings. Case discussion times were recorded for 2312 patients, at a total of 286 TB meetings. Significant decreases were observed in the average case discussion time for the breast and GI TBs. We observed a trend for reduction in discussion time variance for all TBs, suggesting the potential of the digital solution to standardize case discussion via provision of uniform case presentation and data access. Postponement rate decreased from 23 to 10% for ENT TB. This study demonstrated that the digital solution enhanced effective TB implementation, with heterogeneity across cancer types.

Power electronics are crucial elements in more-electric aircraft (MEA) applications. Existing hardware is almost exclusively silicon (Si)-based. However, recent advances in semiconductor technology yielded silicon carbide (SiC) components with current ratings suitable for aerospace applications. These devices have much strength that can increase power density and improve performance over Si-based hardware. High switching speeds are characteristic of SiC devices, and there is much concern about their impact on electromagnetic interference (EMI). This may necessitate larger EMI filters to comply with EMI standards, which would decrease power density and negate some of SiC’s benefits. The following research explores the tradeoff between efficiency and EMI. It compares the performance of two high-power three-phase converters: one built from SiC MOSFETs and the other from Si IGBTs. The test setup consists of a 250-kW drive stand capable of sourcing and regeneratively sinking power as well as a 40-kVA aerospace rated machine. Experimental results are obtained at a bus voltage of 270-Vdc with power levels exceeding 1.5 p.u. The findings demonstrate comparable EMI performance for Si and SiC under MIL-STD-461 with the SiC converter achieving higher efficiency.

BACKGROUND Previous literature demonstrates increased mortality for traumatic brain injury (TBI) with transfer to a Level II versus Level I trauma center. Our objective was to determine the effect of the most recent American College of Surgeons-Committee on Trauma (ACS-COT) "Resources for the Optimal Care of the Injured Patient" resources manual ("The Orange Book") on outcomes after severe TBI after interfacility transfer to Level I versus Level II center. METHODS Utilizing the Trauma Quality Program Participant Use File of the American College of Surgeons admission year 2017, we identified patients with isolated TBI undergoing interfacility transfer to either Level I or Level II trauma center. Logistic regression was performed to determine independent associations with mortality. RESULTS There were 10,268 (71.6%) transferred to a Level I center and 4,025 (28.4%) were transferred to a Level II center. They were mostly male (61.4%) with a mean ± SD age of 61 ± 20.8 years. Mean Injury Severity Score was 16.3 ± 6.3 and most were injured in a single-level fall (51.5%). Patients transferred to a Level I center were less likely to be White (82.3% vs. 84.7%, 0.002) and more likely to have sustained penetrating trauma (2.7% vs. 1.6%

OBJECTIVES The aims of the study were to identify whether obese women are less appropriately screened for cervical cancer before diagnosis and to explore related cancer outcomes. METHODS We retrospectively reviewed all cervical cancer patients at a single institution between 1986 and 2016 and collected demographic information including age, cancer stage, body mass index (BMI), screening information, and cancer outcomes. Morbid obesity was defined as BMI of 40 kg/m or greater, obesity as BMI of 30 to less than 40 kg/m, and nonobese as BMI of less than 30 kg/m. χ, Fisher exact, and Wilcoxon rank sum tests were used to compare variables between BMI categories. Cox regression models were used to evaluate recurrence-free survival and overall survival (OS). RESULTS A total of 1,080 patients were reviewed, of whom 311 (29.4%) were obese and 107 (10.1%) morbidly obese. A significant association between BMI and cytology screening was evidenced with morbidly obese women having the highest incorrect rate (64.4%), followed by obese (51.5%) and nonobese women (46.0%, p < .01). There was no significant difference in presence of symptoms at presentation (p = .12) or stage (p = .06) between BMI categories. In multivariable analysis of cancer outcomes, higher BMI was associated with worse OS (p < .01) with a hazard ratio of 1.25 (95% CI = 0.92-1.69) for obese women and hazard ratio 2.27 (95% CI = 1.56-3.31) for morbidly obese women relative to normal weight but recurrence-free survival did not differ between BMI groups (p = .07). CONCLUSIONS Our study strengthens evidence that obese and morbidly obese women have disproportionate inappropriate screening before cervical cancer diagnosis, and morbidly obese women have worse OS than their counterparts.

Glioblastoma multiforme (GBM) is impossible to fully remove surgically and almost always recurs at the borders of the resection cavity, while systemic delivery of therapeutic drug levels to the brain tumour is limited by the blood-brain barrier. This research describes the development of a novel formulation of Irinotecan-loaded Drug Eluting Seeds (iDES) for insertion into the margin of the GBM resection cavity to provide a sustained high local dose with reduced systemic toxicities. We used primary GBM cells from both the tumour core and Brain Around the Tumour tissue from recurrent GBM patients to demonstrate that irinotecan is more effective than temozolomide. Irinotecan had a 75% response rate, while only 50% responded to temozolomide. With temozolomide the cell viability was never below 80% whereas irinotecan achieved cell viabilities of less than 44%. The iDES were manufactured using a hot melt extrusion process with accurate irinotecan drug loadings and the same cytotoxicity as unformulated irinotecan. The iDES released irinotecan in a sustained fashion for up to 7 days. However, only the 30, 40 and 50% w/w loaded iDES formulations released the 300 to 1000 μg of irinotecan needed to be effective in vivo. The 30 and 40% w/w iDES formulations containing 10% plasticizer and either 60 or 50% PLGA prolonged survival from 27 to 70 days in a GBM xenograft mouse resection model with no sign of tumour recurrence. The 30% w/w iDES formulations showed equivalent toxicity to a placebo in non-tumour bearing mice. This innovative drug delivery approach could transform the treatment of recurrent GBM patients by improving survival and reducing toxicity.

Health Information Exchange (HIE) exhibits remarkable benefits for patient care such as improving healthcare quality and expediting coordinated care. The Office of the National Coordinator (ONC) for Health Information Technology is seeking patient-centric HIE designs that shift data ownership from providers to patients. There are multiple barriers to patient-centric HIE in the current system, such as security and privacy concerns, data inconsistency, timely access to the right records across multiple healthcare facilities. After investigating the current workflow of HIE, this paper provides a feasible solution to these challenges by utilizing the unique features of blockchain, a distributed ledger technology which is considered "unhackable". Utilizing the smart contract feature, which is a programmable self-executing protocol running on a blockchain, we developed a blockchain model to protect data security and patients' privacy, ensure data provenance, and provide patients full control of their health records. By personalizing data segmentation and an "allowed list" for clinicians to access their data, this design achieves patient-centric HIE. We conducted a large-scale simulation of this patient-centric HIE process and quantitatively evaluated the model's feasibility, stability, security, and robustness.

Purpose The purpose of this study is to assess environmental concern at a Midwest university, analyze trends in concern over time and determine the effect of the development of a campus sustainability office. Design/methodology/approach A multi-question survey was administered through peer-to-peer recruitment from an undergraduate environmental science class each fall from 2010–2017. This exercise was originally developed as a pedagogical exercise on the scientific method. Findings Over eight years, incoming freshmen have expressed more concern that humans are harming the environment and students also express greater concern as they progress through college. Research limitations/implications The first year of the survey (2010) and the year that the lead PI was on sabbatical (2014) saw reduced response rates (∼1%–3% of the student population) compared to 6%–9% of the student population in other years. Practical implications Responses to all of the questions in the survey provide guidance for university administrations and sustainability offices about the concerns of the campus community, awareness about campus efforts and support for sustainability activities on campus. Originality/value Few studies have been published on students’ perspectives on environmental concern and sustainability activities on university campuses. These data provide an overview of environmental concern, perceived government action and empowerment to action over an eight-year period. This approach is recommended as a technique to teach the scientific method in introductory classes and as a means to collect data about student perspectives on sustainability.

The cause of death among high-grade serous ovarian cancer (HGSOC) patients involves passive dissemination of cancer cells within the peritoneal cavity and subsequent implantation of cancer spheroids into adjacent organs. Sushi Domain Containing 2 (SUSD2) encodes a type I transmembrane protein containing several functional domains inherent to adhesion molecules. Previous studies using in vitro methods have indicated that SUSD2 functions as a tumor suppressor in several cancers, including HGSOC. In this study, we generated a HGSOC xenograft mouse model to investigate SUSD2 expression in the context of HGSOC late-stage metastasis and overall survival. OVCAR3 cells with knock-down expression of SUSD2 (OVCAR3 SUSD2-KD) or endogenous expression of SUSD2 (OVCAR3-Non-Targeting (NT)) were injected into the peritoneal cavity of athymic nude mice. Immunohistochemistry analysis was utilized to identify infiltrating cancer cells and metastatic tumors in mouse ovaries, pancreas, spleen, omentum and liver. OVCAR3-NT mice developed significantly less cancer cell infiltrate and tumors in their pancreas and omentum compared to OVCAR3 SUSD2-KD mice. Furthermore, OVCAR3-NT mice displayed a longer median survival when compared to OVCAR3 SUSD2-KD mice (175 days and 185.5 days, respectively; p-value 0.0159). Altogether, the findings generated through the preclinical mouse model suggest that increased SUSD2 expression in HGSOC impedes in vivo metastasis to pancreas and omentum. These results correlate to longer median survival and prove to be consistent with previous findings showing prolonged survival of HGSOC patients with high SUSD2-expressing primary tumors.

This systematic review of 55 trials with low or medium risk of bias examines the benefits and harms of several prescription drugs and supplements for treatment of clinical Alzheimer-type dementia.

Statement of problem Conventional dental diagnostic aids are only partially effective in diagnosing structural defects such as cracks in teeth. A more predictable diagnostic for structural instability in the mouth is needed. Purpose The purpose of this clinical study with an increased population size was to evaluate the effectiveness of diagnosing structural instability by using the quantitative percussion diagnostics (QPD) system and to evaluate the influence of independent variables on the relationship between normal fit error (NFE) and observed structural instability found during the clinical disassembly of teeth. Material and methods Twenty-two participants with 264 sites needing restoration were enrolled in an institutional review board–approved 10-year retrospective clinical study. Each site had been tested with the QPD system before being disassembled microscopically with video documentation, and the clinical disassembly results were recorded on a defect-assessment sheet. The NFE data were separately recorded from the preexisting records. The classification of structural pathology based on the disassembly observations for each of the 264 sites was conducted by the clinical researcher (C.G.S.) who was blinded to the NFE values. Results The 264 sites from 22 patients were classified as 8 in the none group, 87 in the moderate group, and 169 in the severe group based on the disassembly findings. The NFE data for the sites were analyzed by using the predefined NFE cutoffs that were independently generated from the previous cumulative logistic regression and decision tree model. For the cumulative logistic regression, 235 out of 264 sites were correctly classified with an agreement of 0.89 (adjusted 95% CI: 0.83-0.95). The number of correctly classified sites for the decision tree model was 234, and the agreement was also 0.89 (adjusted 95% CI: 0.83-0.94). For both cumulative logistic regression and decision tree models, the overall misclassification rate was less than 20% for any restoration material or restoration type. Therefore, the overall performance of NFE classification was consistently good, regardless of restoration material or type. In addition, the sensitivity of the severe category was above 90% for any restoration material or type for the decision tree model. Conclusions The QPD system was found to be a reliable diagnostic aid for classifying structural damage in the categories of none, moderate, or severe based on clinical disassembly findings under the clinical microscope and NFE values. Furthermore, it was determined that restoration type and restoration design were not significant factors in correlating structural pathology with NFE.

Pre-clinical and clinical studies have shown that engineered tumoricidal neural stem cells (tNSCs) are a promising treatment strategy for the aggressive brain cancer glioblastoma (GBM). Yet, stabilizing human tNSCs within the surgical cavity following GBM resection is a significant challenge. As a critical step toward advancing engineered human NSC therapy for GBM, we used a preclinical variant of the clinically utilized NSC line HB1.F3.CD and mouse models of human GBM resection/recurrence to identify a polymeric scaffold capable of maximizing the transplant, persistence, and tumor kill of NSC therapy for post-surgical GBM. Using kinetic bioluminescence imaging, we found that tNSCs delivered into the mouse surgical cavity wall by direct injection persisted only 3 days. We found that delivery of tNSCs into the cavity on nanofibrous electrospun poly-l-lactic acid scaffolds extended tNSC persistence to 8 days. Modifications to fiber surface coating, diameter, and morphology of the scaffold failed to significantly extend tNSC persistence in the cavity. In contrast, tNSCs delivered into the post-operative cavity on gelatin matrices (GEMs) persisted 8-fold longer as compared to direct injection. GEMs remained permissive to tumor-tropic homing, as tNSCs migrated off the scaffolds and into invasive tumor foci both in vitro and in vivo. To mirror envisioned human brain tumor trials, we engineered tNSCs to express the prodrug/enzyme thymidine kinase (tNSCs(tk)) and transplanted the therapeutic cells in the post-operative cavity of mice bearing resected orthotopic patient-derived GBM xenografts. Following administration of the prodrug ganciclovir, residual tumor volumes in mice receiving GEM/tNSCs were reduced by 10-fold at day 35, and median survival was extended from 31 to 46 days. Taken together, these data begin to define design parameters for effective scaffold/tNSC composites and suggest a new approach to maximizing the efficacy of tNSC therapy in human patient trials.

Speckle tracking echocardiography (STE), and more recently, cardiovascular magnetic resonance myocardial feature tracking (CMR-FT) provides insight into all phases of atrial function. The aim of our study was to compare all phases of RA strain using CMR-FT and STE and also assess the relationship between RA and LA strain. A total of 61 healthy volunteers with mean age of 45 ± 13 years had adequate tracking for analysis on CMR-FT and 2D-STE. Females had larger RA reservoir strain (39 ± 15% vs. 32 ± 13%, p = 0.046) and conduit strain (26 ± 12% vs. 20 ± 9%, p = 0.03) when compared to males, but was not the case with booster strain (14 ± 7% vs. 12 ± 6%, p = 0.45). In comparison with STE derived strain, the RA reservoir and conduit strain were not significantly different between CMR-FT and the three echocardiography gating methods (p > 0.05 for all). Noticeably, there were no significant differences in strain and strain rate between RA and LA function using CMR-FT (p > 0.05 for all). RA strain and strain rate using CMR-FT had fair and good intra- and inter-observer reproducibility and had superior reproducibility compared to STE derived strain.

PURPOSE Plasma circulating tumor human papillomavirus DNA (ctHPVDNA) is a sensitive and specific biomarker of human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC). We investigated whether longitudinal monitoring of ctHPVDNA during post-treatment surveillance could accurately detect clinical disease recurrence. METHODS AND MATERIALS A prospective biomarker clinical trial was conducted among patients with nonmetastatic HPV-associated (p16-positive) OPSCC. All patients were treated with curative-intent chemoradiotherapy (CRT). Patients underwent a 3-month post-CRT positron emission tomography/computed tomography scan and were thereafter clinically evaluated every 2-4 months (years 1-2), then every 6 months (years 3-5). Chest imaging was performed every 6 months. Blood specimens were collected every 6-9 months for analysis of plasma ctHPVDNA using a multianalyte digital polymerase chain reaction assay. The primary endpoint was to estimate the negative predictive value (NPV) and positive predictive value (PPV) of ctHPVDNA surveillance. RESULTS One hundred fifteen patients were enrolled, and 1,006 blood samples were analyzed. After a median follow-up time of 23 months (range, 6.1-54.7 months), 15 patients (13%) developed disease recurrence. Eighty-seven patients had undetectable ctHPVDNA at all post-treatment time points, and none developed recurrence (NPV, 100%; 95% CI, 96% to 100%). Twenty-eight patients developed a positive ctHPVDNA during post-treatment surveillance, 15 of whom were diagnosed with biopsy-proven recurrence. Sixteen patients had 2 consecutively positive ctHPVDNA blood tests, 15 of whom developed biopsy-proven recurrence. Two consecutively positive ctHPVDNA blood tests had a PPV of 94% (95% CI, 70% to 99%). Median lead time between ctHPVDNA positivity and biopsy-proven recurrence was 3.9 months (range, 0.37-12.9 months). CONCLUSION Detection of ctHPVDNA in two consecutive plasma samples during post-treatment surveillance has high PPV and NPV for identifying disease recurrence in patients with HPV-associated oropharyngeal cancer and may facilitate earlier initiation of salvage therapy.

Purpose The purpose of this study was to explore college students’ understanding of sustainability and, specifically, the extent to which students see social justice as being integral to sustainability. Design/methodology/approach Between fall 2015 and 2017, an online survey study was deployed to students at a Midwestern University in the USA to assess attitudes and concerns about environmental issues and awareness of the university’s activities related to these issues. This analysis included ten assessment items from a larger study, of which 1,929 participants were included in the final sample. A chi-square goodness-of-fit and variable cluster analysis were performed on the included items. Findings Items such as “recycling,” “economic viability” and “fair treatment of all” were identified as integral to the concept of sustainability, while items such as “growing organic vegetables” and “reducing meat consumption” had high levels of “not applicable” and “don’t know” responses, with differences arising across gender and class standing. Social justice-related items were seen as more distally connected to sustainability. Research limitations/implications This study is limited by a non-random sample of students. Practical implications College students tend not to recognize the integral nature of social justice or the relevance of food to sustainability, providing an opportunity for universities to better prepare their students for a sustainable future. Social implications Universities might adopt policies and curricula that address these areas of ignorance. Originality/value This study is among the first to identify specific areas of college students’ lack of understanding about sustainability.

A unique challenge in some brain tumor patients is the fact that tumors arising in certain areas of the brain involve the neural structures of consciousness or alertness, limiting the patient’s ability to participate in rehabilitation following surgery. A critical question is whether neurostimulant therapy can help patients participate in rehabilitation efforts. We performed a retrospective review of all patients undergoing brain tumor surgery by the senior author from 2012 to 2018. We limited this study to patients with tumors occupying critical structures related to consciousness, alertness, and motor initiation. A combination of methylphenidate and levodopa/carbidopa was used to monitor the progress of patients through neurorehabilitation efforts. We identified 101 patients who experienced an inability to participate in rehabilitation (ITPR) in the post-operative period. Of these, 86 patients (85%) were treated with methylphenidate and levodopa/carbidopa. Cases of ITPR were related to dysfunction of the brainstem (12/86 cases, 14%), thalamus (17/86 cases, 20%), hypothalamus (14/86 cases, 16%), basal ganglia (13/86 cases, 15%), and medial frontal lobe (30/86 cases, 35%). Of the 86 individuals treated, 47/86 patients (55%) showed early improvement in their ability to participate with rehabilitation. At three month follow-up, 58/86 patients (67%) had returned to living independently or were at least interactive and cooperative during follow-up examination. This feasibility report suggests that combined therapy with methylphenidate and levodopa/carbidopa may help patients participate in neurorehabilitation efforts in the immediate post-operative period following brain tumor surgery. Randomized, controlled clinical trials are needed to explore this concept more thoroughly.

Chronic use of opioids can produce opioid-induced hyperalgesia (OIH), and when used to treat migraine, these drugs can result in increased pain and headache chronicity. We hypothesized that overlapping mechanisms between OIH and chronic migraine occur through neuropeptide dysregulation. Using label-free, non-biased liquid chromatography-mass spectrometry to identify and measure changes in more than 1500 neuropeptides under these two conditions, we observed only 16 neuropeptides that were altered between the two conditions. The known pro-migraine molecule, calcitonin-gene related peptide, was among seven peptides associated with chronic migraine, with several pain-processing neuropeptides among the nine other peptides affected in OIH. Further, composite peptide complements Pituitary adenylate cyclase-activating polypeptide (PACAP), Vasoactive intestinal peptide (VIP) and Secretogranin (SCG) showed significant changes in both chronic migraine and OIH. In a follow-up pharmacological study, we confirmed the role of PACAP in models of these two disorders, validating the effectiveness of our peptidomic approach, and identifying PACAP as a mechanistic link between chronic migraine and OIH. Data are available via ProteomeXchange with identifier PXD013362.

Hepatocellular carcinoma (HCC) is a leading cause of cancer mortality worldwide with no clinically confirmed oncogenic driver. Although preclinical studies implicate the FGF19 receptor FGFR4 in hepatocarcinogenesis, the dependence of human cancer on FGFR4 has not been demonstrated. Fisogatinib (BLU-554) is a potent and selective inhibitor of FGFR4 and demonstrates clinical benefit and tumor regression in patients with HCC with aberrant FGF19 expression. Mutations were identified in the gatekeeper and hinge-1 residues in the kinase domain of FGFR4 upon disease progression in 2 patients treated with fisogatinib, which were confirmed to mediate resistance in vitro and in vivo. A gatekeeper-agnostic, pan-FGFR inhibitor decreased HCC xenograft growth in the presence of these mutations, demonstrating continued FGF19–FGFR4 pathway dependence. These results validate FGFR4 as an oncogenic driver and warrant further therapeutic targeting of this kinase in the clinic. Significance: Our study is the first to demonstrate on-target FGFR4 kinase domain mutations as a mechanism of acquired clinical resistance to targeted therapy. This further establishes FGF19–FGFR4 pathway activation as an oncogenic driver. These findings support further investigation of fisogatinib in HCC and inform the profile of potential next-generation inhibitors. See related commentary by Subbiah and Pal, p. 1646. This article is highlighted in the In This Issue feature, p. 1631

BACKGROUND Induced neural stem cells (iNSCs) have emerged as a promising therapeutic platform for glioblastoma (GBM). iNSCs have the innate ability to home to tumor foci, making them ideal carriers for anti-tumor payloads. However, iNSC persist for only two weeks in the murine GBM tumor resection cavity. We hypothesized that by encapsulating iNSCs in a scaffold matrix, we could increase both the persistence of the cells the therapeutic durability. METHODS iNSCs expressing TRAIL were encapsulated in a gelatin-thrombin matrix; fibrinogen was used to polymerize the matrix. SEM was used to explore interactions between iNSCs and the scaffold matrix. To evaluate persistence, iNSCs encapsulated in the matrix were implanted into mock resection cavities of athymic nude mice and followed via BLI. To study the impacts of encapsulation on iNSC efficacy, athymic nude mice were implanted with U87 or GBM8 tumors. Tumors were then resected, and iNSCs encapsulated in the matrix were implanted; tumor volume was monitored via BLI. RESULTS SEM images showed homogeneous distribution of iNSCs throughout the matrix; iNSCs were completed encased in the fibrin clot component of the matrix and did not adhere to gelatin. In vivo, encapsulated iNSCs persisted for nearly 100 days whereas iNSCs directly injected into the brain parenchyma persisted < 20 days. Using mice bearing GBM8 tumors, animals treated with a high dose of therapeutic encapsulated iNSCs survived ~60 days longer than animals treated with non-therapeutic cells. A similar trend was observed in animals inoculated with U87 tumors. While not statistically significant, 25% of mice treated with iNSCs encapsulated in the gelatin-thrombin matrix survived longer than those treated with iNSCs encapsulated in a fibrin-only matrix, suggesting additional benefit due to the gelatin component. FUTURE DIRECTIONS: Prospective experiments will explore the impact of the scaffold on iNSC phenotype, including proliferation, differentiation, and migration markers.

SIGNIFICANCE Retinal migraine and migrainous infarction are distinct clinical entities delineated by the International Headache Society. Presented is a novel case report demonstrating unique optical coherence tomography evidence of retinal ischemia experienced during a migraine with effects across retinal vascular territories. This may represent evidence of migrainous infarction within the retina. PURPOSE The purpose of this study is to present clinical and quasi-histologic optical coherence tomography features of retinal ischemia associated with migraine. CASE REPORT Presented is a case of profound monocular vision loss coincident with a migraine episode. Optical coherence tomography with novel features of acute inner retinal thinning, increased delineation of the inner plexiform and outer plexiform layers, and increased signal intensity of the photoreceptor layer is reported. These discriminating characteristics contrast those of retinal artery occlusions and other primary ocular vasculopathies such as Susac syndrome and acute macular neuroretinopathies. CONCLUSIONS A case of permanent vision loss with retinal thinning and ischemic hyperreflectivity of retinal layers on optical coherence tomography in different vascular territories is shown to be associated with migraine. These features may provide clinical evidence of migrainous pathophysiology within the retina.

The objective was to compare the repeatability between dental faculty, whose clinical practice was primarily restorative dentistry, and final year dental students in categorizing the inherent translucency of images selected at random using either a 3- or 7-point scale (translucent to opaque). Digital images of anterior dentition were randomly selected based on inherent translucency. Thirty images (five were repeated) were randomized and categorized by 20 dental students and 20 faculty on their inherent translucency. Statistical analysis was performed using an F test for analysis of variance at 95% confidence interval. A covariance parameter estimate (CPE) was accomplished to compare the inter-rater variability of the dental faculty and dental students. Statistically, more variability occurred between Slides (CPE of 0.185 (p = 0.001)) and between Subject and Slide (CPE of 0.122 (p = 0.0002)) than within subjects (CPE of 0.021 (p = 0.083)). Viewing repeat Slides, Students (CPE = 0.16) were more consistent (p &lt, 0.05) than faculty (CPE = 1.8) using the 3- point scale, while the CPE was the same (CPE = 0.669) using 7-point scale. Dental students and faculty were consistent using the 7-point scale to judge repeat slides, while dental students in this limited pilot study were more consistent when viewing a repeat slide using the 3-point scale.

INTRODUCTION AND OBJECTIVE:Prior studies have demonstrated the safety of same-day discharge (SDD) following robotic prostatectomy using the multiport robot. At our institution, the da Vinci Single-...

IMPORTANCE: There is limited information about trends in the treatment of opioid use disorder (OUD) among Medicaid enrollees. OBJECTIVE: To examine the use of medications for OUD and potential indicators of quality of care in multiple states. DESIGN, SETTING, AND PARTICIPANTS: Exploratory serial cross-sectional study of 1 024 301 Medicaid enrollees in 11 states aged 12 through 64 years (not eligible for Medicare) with International Classification of Diseases, Ninth Revision (ICD-9 or ICD-10) codes for OUD from 2014 through 2018. Each state used generalized estimating equations to estimate associations between enrollee characteristics and outcome measure prevalence, subsequently pooled to generate global estimates using random effects meta-analyses. EXPOSURES: Calendar year, demographic characteristics, eligibility groups, and comorbidities. MAIN OUTCOMES AND MEASURES: Use of medications for OUD (buprenorphine, methadone, or naltrexone); potential indicators of good quality (OUD medication continuity for 180 days, behavioral health counseling, urine drug tests); potential indicators of poor quality (prescribing of opioid analgesics and benzodiazepines). RESULTS: In 2018, 41.7% of Medicaid enrollees with OUD were aged 21 through 34 years, 51.2% were female, 76.1% were non-Hispanic White, 50.7% were eligible through Medicaid expansion, and 50.6% had other substance use disorders. Prevalence of OUD increased in these 11 states from 3.3% (290 628 of 8 737 082) in 2014 to 5.0% (527 983 of 10 585 790) in 2018. The pooled prevalence of enrollees with OUD receiving medication treatment increased from 47.8% in 2014 (range across states, 35.3% to 74.5%) to 57.1% in 2018 (range, 45.7% to 71.7%). The overall prevalence of enrollees receiving 180 days of continuous medications for OUD did not significantly change from the 2014-2015 to 2017-2018 periods (−0.01 prevalence difference, 95% CI, −0.03 to 0.02) with state variability in trend (90% prediction interval, −0.08 to 0.06). Non-Hispanic Black enrollees had lower OUD medication use than White enrollees (prevalence ratio [PR], 0.72; 95% CI, 0.64 to 0.81; P

A prevalent challenge in underdeveloped countries is the mapping and accounting of certain sub-populations for public health matters. This is especially true in sub-Saharan African countries that lack specific resources and technologies. Often, international non-profit groups provide targeted support for populations' health on specific matters, such as clean water initiatives and basic health clinics. This is especially critical in various ethnic populations that are not well integrated into a country's existing public health services. In countries such as Tanzania, one such ethnic population is the Maasai people. In this paper, we demonstrate how machine learning algorithms, combined with remote sensing data, can aid non-profit health delivery organizations to map Maasailand boma homesteads in northern Tanzania. Our study area encompasses over 3900 square kilometers of Massailand, where we have manually identified 635 bomas. We have evaluated four different deep neural network architectures for their ability to recognize boma, ResNet50, Xception, Inception-ResNet-V2, and ProxylessNAS, with cross-validation F1 scores of 95.32%, 95.45%, 96.78%, and 97.28%, respectively.

Objectives The Coronavirus Disease 2019 pandemic has affected the health care system significantly. We compare 2019 to 2020 to evaluate how trauma encounters has changed during the pandemic. Methods Retrospective analysis using a large US health care system to compare trauma demographics, volumes, mechanisms of injury, and outcomes. Statistical analysis was used to evaluate for significant differences comparing 2019 to 2020. Results Data was collected from 88 hospitals across 18 states. 169 892 patients were included in the study. There were 6.3% fewer trauma patient encounters in 2020 compared to 2019. Mechanism of injury was significantly different between 2019 and 2020 with less blunt injuries (89.64% vs. 88.39%, P < .001), more burn injuries (1.84% vs. 2.00%, P = .021), and more penetrating injuries (8.58% vs. 9.75%, P < .001). Compared to 2019, patients in 2020 had higher mortality (2.62% vs. 2.88%, P < .001), and longer hospital LOS (3.92 ± 6.90 vs. 4.06 ± 6.56, P < .001). Conclusion The COVID-19 pandemic has significantly affected trauma patient demographics, LOS, mechanism of injury, and mortality.

The use of telemedicine continues to grow as more patients are receptive to this innovative way of providing health care. Multiple publications in telemedicine indicated high satisfaction for this service. This study focuses on the use of telemedicine in a pediatric urology clinic and examines 3 research questions: (1) How did patients’ parents/guardians feel about their video appointments? (2) What were the experiences of novice telemedicine providers conducting postsurgical appointments via video? and (3) How did novice telemedicine providers’ experiences compare to those of expert telemedicine providers?

Rationale: Data on the molecular mechanisms that regulate platelet–pulmonary endothelial adhesion under conditions of hypoxia are lacking, but may have important therapeutic implications. Objectives: To identify a hypoxia-sensitive, modifiable mediator of platelet–pulmonary artery endothelial cell adhesion and thrombotic remodeling. Methods: Network medicine was used to profile protein–protein interactions in hypoxia-treated human pulmonary artery endothelial cells. Data from liquid chromatography–mass spectrometry and microscale thermophoresis informed the development of a novel antibody (Ab) to inhibit platelet–endothelial adhesion, which was tested in cells from patients with chronic thromboembolic pulmonary hypertension (CTEPH) and three animal models in vivo. Measurements and Main Results: The protein NEDD9 was identified in the hypoxia thrombosome network in silico. Compared with normoxia, hypoxia (0.2% O(2)) for 24 hours increased HIF-1α (hypoxia-inducible factor-1α)–dependent NEDD9 upregulation in vitro. Increased NEDD9 was localized to the plasma-membrane surface of cells from control donors and patients with CTEPH. In endarterectomy specimens, NEDD9 colocalized with the platelet surface adhesion molecule P-selectin. Our custom-made anti-NEDD9 Ab targeted the NEDD9–P-selectin interaction and inhibited the adhesion of activated platelets to pulmonary artery endothelial cells from control donors in vitro and from patients with CTEPH ex vivo. Compared with control mice, platelet–pulmonary endothelial aggregates and pulmonary hypertension induced by ADP were decreased in NEDD9(−/−) mice or wild-type mice treated with the anti-NEDD9 Ab, which also decreased chronic pulmonary thromboembolic remodeling in vivo. Conclusions: The NEDD9–P-selectin protein–protein interaction is a modifiable target with which to inhibit platelet–pulmonary endothelial adhesion and thromboembolic vascular remodeling, with potential therapeutic implications for patients with disorders of increased hypoxia signaling pathways, including CTEPH.

Dry eye is not typically considered a toxicity of whole brain radiation therapy (WBRT). We analyzed dry eye syndrome as part of a prospective study of patient-reported outcomes after WBRT.Patients receiving WBRT to 25 to 40 Gy were enrolled on a study with dry mouth as the primary endpoint and dry eye syndrome as a secondary endpoint. Patients received 3-dimensional WBRT using opposed lateral fields. Per standard practice, lacrimal glands were not prospectively delineated. Patients completed the Subjective Evaluation of Symptom of Dryness (SESoD, scored 0-4, with higher scores representing worse dry eye symptoms) at baseline, immediately after WBRT (EndRT), and at 1 month (1M), 3 months, and 6 months. Patients with baseline SESoD ≥3 (moderate dry eye) were excluded. The endpoints analyzed were ≥1-point and ≥2-point increase in SESoD score at 1M. Lacrimal glands were retrospectively delineated with fused magnetic resonance imaging scans.One hundred patients were enrolled, 70 were eligible for analysis, and 54 were evaluable at 1M. Median bilateral lacrimal V20Gy was 79%. At 1M, 17 patients (32%) had a ≥1-point increase in SESoD score, and 13 (24%) a ≥2-point increase. Lacrimal doses appeared to be associated with an increase in SESoD score of both ≥1 point (V10Gy: P = .042, odds ratio [OR] 1.09/%; V20Gy: P = .071, OR 1.03/%) and ≥2 points (V10Gy: P = .038, OR 1.15/%; V20Gy: P = .063, OR 1.04/%). The proportion with increase in dry eye symptoms at 1M for lacrimal V20Gy ≥79% versus79% was 46% versus 15%, respectively, for ≥1 point SESoD increase (P = .02) and 36% versus 12%, respectively, for ≥2 point SESoD increase (P = .056).Dry eye appears to be a relatively common, dose/volume-dependent acute toxicity of WBRT. Minimization of lacrimal gland dose may reduce this toxicity, and patients should be counseled regarding the existence of this potential side effect and treatments for dry eye.

Headaches are highly disabling and are among the most common neurological disorders worldwide. Despite the high prevalence of headache, therapeutic options are limited. We recently identified the delta opioid receptor (DOR) as an emerging therapeutic target for migraine. In this study, we examined the effectiveness of a hallmark DOR agonist, SNC80, in disease models reflecting diverse headache disorders including: chronic migraine, post-traumatic headache (PTH), medication overuse headache by triptans (MOH), and opioid-induced hyperalgesia (OIH). To model chronic migraine C57BL/6J mice received chronic intermittent treatment with the known human migraine trigger, nitroglycerin. PTH was modeled by combining the closed head weight drop model with the nitroglycerin model of chronic migraine. For MOH and OIH, mice were chronically treated with sumatriptan or morphine, respectively. The development of periorbital and peripheral allodynia was observed in all four models; and SNC80 significantly inhibited allodynia in all cases. In addition, we also determined if chronic daily treatment with SNC80 would induce MOH/OIH, and we observed limited hyperalgesia relative to sumatriptan or morphine. Together, our results indicate that DOR agonists could be effective in multiple headache disorders, despite their distinct etiology, thus presenting a novel therapeutic target for headache.

In the setting of increasing restrictions to legal abortion in the United States, reports have emerged of self-induced termination of pregnancies with misoprostol, obtained without a prescription or provider. This study seeks to describe the prevalence of women seeking or employing misoprostol for self-induced abortion, and how they access information. In a cross-sectional study of women immediately following their abortion at three reproductive health clinics in the Midwestern United States, an anonymous survey queried gestational age, barriers, online investigation about self-induction and opinions concerning the availability of medical abortion. From June to September 2016, 276 women participated out of 437 presenting to the clinics during the study period. One hundred and ninety-one (74.6%) women had investigated abortion options online, and of those, 58 (30.9%) investigated misoprostol online, for home use. Women who investigated online options were less likely to have had a prior abortion than those who did not investigate online (29.3% vs. 63.1%, p

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has risen to the level of a global pandemic. Growing evidence has proven the cardiac involvement in SARS-CoV-2 infection. This study aims to evaluate the ability of cardiovascular complications determined by elevated troponin and electrocardiogram findings (e.g., corrected QT interval (QTc)) in predicting the severity of SARS-CoV-2 infection among hospitalized patients. Methods: This is a retrospective review of medical records of 800 patients, admitted to Richmond University Medical Center in Staten Island, NY, and tested positive for SARS-CoV-2 between March 1, 2020 and July 31, 2020. A total of 339 patients met the study inclusion and exclusion criteria and were included in statistical analysis. Results: Elevated serum troponin levels on admission statistically correlated with mortality in SARS-CoV-2 patients. Prolonged QTc was shown to have an independent statistically significant association with mortality among patients hospitalized with SARS-CoV-2. Conclusions: Growing concern for cardiovascular sequelae of coronavirus disease 2019 (COVID-19) has prompted many researchers to investigate the role of cardiovascular complications in mortality due to SARS-CoV-2. Obtaining a simple electrocardiogram for hospitalized patients with COVID-19 could provide an independent prognostic tool and prompt more coordinated treatment strategies to prevent mortality among patients hospitalized with COVID-19. Cardiol Res. 2021;12(4):258-264 doi: https://doi.org/10.14740/cr1276

IntroductionDirect-to-family clinical trials efficiently provide data while reducing the participation burden for children and their families. Although these trials can offer significant advantages over traditional clinical trials, the process of designing and implementing direct-to-family studies is poorly defined, especially in children with rheumatic disease. This paper provides lessons learnt from the design and implementation of a self-controlled, direct-to-family pilot trial aimed to evaluate the effects of a medication management device on adherence to hydroxychloroquine in paediatric SLE.MethodsSeveral design features accommodate a direct-to-family approach. Participants meeting eligibility criteria from across the USA were identified a priori through a disease registry, and all outcome data are collected remotely. The primary outcome (medication adherence) is evaluated using electronic medication event-monitoring, plasma drug levels, patient questionnaires and pill counts. Secondary and exploratory endpoints include (1) lupus disease activity measured by a remote SLE Disease Activity Index examination and the Systemic Lupus Activity Questionnaire; and (2) hydroxychloroquine pharmacokinetics and pharmacodynamics. Recruitment of the initial target of 20 participants was achieved within 10 days. Due to initial recruitment success, enrolment was increased to 26 participants. Additional participants who were interested were placed on a waiting list in case of dropouts during the study.Discussion and disseminationDirect-to-family trials offer several advantages but present unique challenges. Lessons learnt from the protocol development, design, and implementation of this trial will inform future direct-to-family trials for children and adults with rheumatic diseases. Additionally, the data collected remotely in this trial will provide critical information regarding the accuracy of teleresearch in lupus, the impact of adherence to hydroxychloroquine on disease activity and a pharmacokinetic analysis to inform paediatric-specific dosing of hydroxychloroquine.Trial registration numberClinicalTrials.gov Registry (NCT04358302).

Background Studies show increased early and overall mortality at level II compared to level I trauma centers in hemodynamically unstable patients. We hypothesize there is no mortality difference between level I and level II centers applying more contemporary data. Study design Utilizing the 2017 Trauma Quality Program Participant Use File (TQP-PUF), we identified adult patients (age >14 years) who presented to an American College of Surgeons (ACS) verified level I or II center with hypotension (systolic blood pressure [SBP] < 90 mmHg). Logistic regression was performed to identify adjusted associations with mortality. Results A total of 7,264 patients met the inclusion criteria, of whom most were males (4,924 [67.8%]) with blunt trauma (5,924 [81.6%]) being predominated. Mean admission SBP was 73.2 (±13.0) mmHg. There were 1,097 (15.1%) deaths. Level I admissions (4,931 (67.9%]) were more likely male (3,389 [68.7%] vs. 1,535 [65.8]; p=0.012), non-white (3,119 [63.3%] vs. 1,664 [71.3%]; p

Iliac vein injury in the absence of pelvic fractures is rare. We present the case of a 27-year-old male involved in a motorcycle crash. Imaging demonstrated a lumbar hernia and pelvic hematoma in the absence of pelvic fractures. The patient became unstable and required emergency surgery demonstrating an iliac vein injury requiring ligation. Diagnosis and management of this rare injury is reviewed.

Migraine is the sixth most prevalent disease worldwide but the mechanisms that underlie migraine chronicity are poorly understood. Cytoskeletal flexibility is fundamental to neuronal-plasticity and is dependent on dynamic microtubules. Histone-deacetylase-6 (HDAC6) decreases microtubule dynamics by deacetylating its primary substrate, α-tubulin. We use validated mouse models of migraine to show that HDAC6-inhibition is a promising migraine treatment and reveal an undiscovered cytoarchitectural basis for migraine chronicity. The human migraine trigger, nitroglycerin, produced chronic migraine-associated pain and decreased neurite growth in headache-processing regions, which were reversed by HDAC6 inhibition. Cortical spreading depression (CSD), a physiological correlate of migraine aura, also decreased cortical neurite growth, while HDAC6-inhibitor restored neuronal complexity and decreased CSD. Importantly, a calcitonin gene-related peptide receptor antagonist also restored blunted neuronal complexity induced by nitroglycerin. Our results demonstrate that disruptions in neuronal cytoarchitecture are a feature of chronic migraine, and effective migraine therapies might include agents that restore microtubule/neuronal plasticity., eLife digest Migraines are a common brain disorder that affects 14% of the world’s population. For many people the main symptom of a migraine is a painful headache, often on one side of the head. Other symptoms include increased sensitivity to light or sound, disturbed vision, and feeling sick. These sensory disturbances are called aura and they often occur before the headache begins. One particularly debilitating subset of migraines are chronic migraines, in which patients experience more than 15 headache days per month. Migraine therapies are often only partially effective or poorly tolerated, making it important to develop new drugs for this condition, but unfortunately, little is known about the molecular causes of migraines. To bridge this gap, Bertels et al. used two different approaches to cause migraine-like symptoms in mice. One approach consisted on giving mice nitroglycerin, which dilates blood vessels, produces hypersensitivity to touch, and causes photophobia in both humans and mice. In the second approach, mice underwent surgery and potassium chloride was applied onto the dura, a thick membrane that surrounds the brain. This produces cortical spreading depression, an event that is linked to migraine auras and involves a wave of electric changes in brain cells that slowly propagates across the brain, silencing brain electrical activity for several minutes. Using these approaches, Bertels et al. studied whether causing chronic migraine-like symptoms in mice is associated with changes in the structures of neurons, focusing on the effects of migraines on microtubules. Microtubules are cylindrical protein structures formed by the assembly of smaller protein units. In most cells, microtubules assemble and disassemble depending on what the cell needs. Neurons need stable microtubules to establish connections with other neurons. The experiments showed that provoking chronic migraines in mice led to a reduction in the numbers of connections between different neurons. Additionally, Bertels et al. found that inhibiting HDAC6 (a protein that destabilizes microtubules) reverses the structural changes in neurons caused by migraines and decreases migraine symptoms. The same effects are seen when a known migraine treatment strategy, known as CGRP receptor blockade, is applied. These results suggest that chronic migraines may involve decreased neural complexity, and that the restoration of this complexity by HDAC6 inhibitors could be a potential therapeutic strategy for migraine.