Vertebral Body Reshaping after Fractures: An Important Index of Recovery in Glucocorticoid-Treated Children.

PURPOSE: In this 6-year study we identified factors associated with spontaneous vertebral body reshaping in glucocorticoid (GC)-treated children with leukemia, rheumatic disorders, and nephrotic syndrome. METHODS: Subjects were 79 children (mean age 7.4 years) who had vertebral fracture (VF) evaluation on lateral spine radiographs at least 1 year after VF detection. VF were graded using the modified Genant semiquantitative method and fracture burden for individuals was quantified using the spinal deformity index (SDI; sum of grades from T4 to L4). RESULTS: Sixty-five children (82.3%) underwent complete vertebral body reshaping (median time from VF detection to complete reshaping 1.3 years by Cox proportional hazard modeling). Of 237 VF, the majority (83.1%) ultimately reshaped, with 87.2% reshaping in the thoracic region vs 70.7% in the lumbar region (P = .004). Cox models showed that (1) every g/m2 increase in GC exposure in the first year after VF detection was associated with a 19% decline in the probability of reshaping; (2) each unit increase in the SDI at the time of VF detection was associated with a 19% decline in the probability of reshaping [hazard ratio (HR) = 0.81; 95% confidence interval (CI) = 0.71, 0.92; P = .001]; (3) each additional VF present at the time of VF detection reduced reshaping by 25% (HR = 0.75; 95% CI = 0.62, 0.90; P = .002); and (4) each higher grade of VF severity decreased reshaping by 65% (HR = 0.35; 95% CI = 0.21, 0.57; P < .001). CONCLUSION: After experiencing a VF, children with higher GC exposure, higher SDI, more severe fractures, or lumbar VF were at increased risk for persistent vertebral deformity.

A modular circuit architecture coordinates the diversification of courtship strategies in Drosophila.

Identifying a mate is a central imperative for males of most species but poses the challenge of distinguishing a suitable partner from an array of potential male competitors or females of related species. Mate recognition systems are thus subject to strong selective pressures, driving the rapid coevolution of female sensory cues and male sensory preferences. Here we leverage the rapid evolution of female pheromones across the Drosophila genus to gain insight into how males coordinately adapt their detection and interpretation of these chemical cues to hone their mating strategies. While in some Drosophila species females produce unique pheromones that act to attract and arouse their conspecific males, the pheromones of most species are sexually monomorphic such that females possess no distinguishing chemosensory signatures that males can use for mate recognition. By comparing several close and distantly-related Drosophila species, we reveal that D. yakuba males have evolved the distinct ability to use a sexually-monomorphic pheromone, 7-tricosene (7-T), as an excitatory cue to promote courtship, a sensory innovation that enables D. yakuba males to court in the dark thereby expanding their reproductive opportunities. To gain insight into the neural adaptations that enable 7-T to act as an excitatory cue, we compared the functional properties of two key nodes within the pheromone circuits of D. yakuba and a subset of its closest relatives. We show that the instructive role of 7-T in D. yakuba arises from concurrent peripheral and central circuit changes: a distinct subpopulation of sensory neurons has acquired sensitivity to 7-T which in turn selectively signals to a distinct subset of P1 neurons in the central brain that trigger courtship behaviors. Such a modular circuit organization, in which different sensory inputs can independently couple to multiple parallel courtship control nodes, may facilitate the evolution of mate recognition systems by allowing males to take advantage of novel sensory modalities to become aroused. Together, our findings suggest how peripheral and central circuit adaptations can be flexibly linked to underlie the rapid evolution of mate recognition and courtship strategies across species.

Upper lumbar spine far lateral disc herniations masquerading as peripheral nerve sheath tumors: illustrative cases.

BACKGROUND: Migratory disc herniations can mimic neoplasms clinically and on imaging. Far lateral lumbar disc herniations usually compress the exiting nerve root and can be challenging to distinguish from a nerve sheath tumor due to the proximity of the nerve and characteristics on magnetic resonance imaging (MRI). These lesions can occasionally present in the upper lumbar spine region at the L1-2 and L2-3 levels. OBSERVATIONS: The authors describe 2 extraforaminal lesions in the far lateral space at the L1-2 and L2-3 levels, respectively. On MRI, both lesions tracked along the corresponding exiting nerve roots with avid postcontrast rim enhancement and edema in the adjacent muscle tissue. Thus, they were initially concerning for peripheral nerve sheath tumors. One patient underwent fluorodeoxyglucose positron emission tomography-computed tomography (FDG PET-CT) screening and demonstrated moderate FDG uptake on PET-CT scan. In both cases, intraoperative and postoperative pathology revealed fibrocartilage disc fragments. LESSONS: Differential diagnosis for lumbar far lateral lesions that are peripherally enhancing on MRI should include migratory disc herniation, regardless of the level of the disc herniations. Accurate preoperative diagnosis can aid in decision making for management, surgical approach, and resection.

Patterns of paediatric massive blood transfusion protocol use in trauma and non-trauma patients.

BACKGROUND: Massive blood transfusion is infrequently required by children but can be a lifesaving intervention for haemorrhage or coagulopathy. Product volumes and ratios administered during the initiation of paediatric massive blood transfusion protocol (MBTP) are highly variable and the optimal component ratio is unknown. METHODS/MATERIALS: We performed a single-centre retrospective chart review of patients (<20 years) who received MBTP activation from August 2012 through January 2018. Logistic regression was used to determine the association between MBTP use characteristics (including blood product type and volume transfused, extracorporeal membrane oxygenation [ECMO] support, and cardiac arrest occurrence) and 24-h mortality. "Low" product ratio was defined as a ratio of plasma or platelets to red blood cells (RBCs) of <1:2 and "high" as ≥1:2. RESULTS: Ninety-eight MBTPs were activated for 89 patients (range 1-4 per patient). The most common underlying diagnoses were congenital heart disease (CHD, n = 28, 31.5%), followed by cardiopulmonary disease, and trauma. CHD patients required the greatest volume of RBCs (226.3 ml/kg, 95%CI [160.0, 292.7], p = 0.002) and platelets (46.7 ml/kg, 95%CI [33.2, 60.2], p < 0.001). A "low" product ratio was more common for the MBTP, with its incidence similar among the underlying diagnoses. CONCLUSION: An MBTP developed for trauma patients can be applied to non-trauma patients but standard MBTP components may not be optimal for all children. These findings show that underlying patient diagnoses may be a factor when designing an MBTP for a heterogeneous paediatric population.

Relationship between hormonal contraceptives and sleep among women of reproductive age: a systematic review protocol.

INTRODUCTION: The aetiology of sleep disruptions is unknown, but hormonal fluctuations during the menstrual cycle, pregnancy and menopause have been shown to potentially affect how well a woman sleeps. The aim of this systematic review was to investigate whether hormonal contraceptives are associated with a decreased quality of sleep and increased sleep duration in women of reproductive age. METHODS: This review will analyse data from randomised controlled trials or non-randomised comparative studies investigating the association between hormonal contraceptives and sleep outcomes among women of reproductive age. Reviews addressing the same research question with similar eligibility criteria will be included. A literature search will be performed using the MEDLINE, Embase and Cochrane Central Register of Controlled Trials databases from inception to 7 March 2021. The Cochrane Collaboration's Risk of Bias for Randomised Trials V.2.0 and The Risk of Bias for Non-randomised Studies of Interventions tool will be used to assess risk of bias for each outcome in eligible studies. Two reviewers will independently assess eligibility of studies and risk of bias and extract the data. All extracted data will be presented in tables and narrative form. For sleep measures investigated by two or more studies with low heterogeneity, we will conduct random-effects meta-analysis to estimate the magnitude of the overall effect of hormonal contraceptives. If studies included in this systematic review form a connected network, a network meta-analysis will be conducted to estimate the comparative effect of different contraceptives. The Grading of Recommendations, Assessment, Development, and Evaluation approach will be used to summarise the quality of evidence. Our protocol follows the Preferred Reporting Items for Systematic Reviews and Meta-Analyses for Protocols 2015 guidelines. ETHICS AND DISSEMINATION: Ethics approval is not required as data were sourced from previously reported studies. The findings of this review will be published in a peer-reviewed journal and presented at relevant conferences. PROSPERO REGISTRATION NUMBER: CRD42020199958.

Assessment of Nonroutine Events During Intubation After Pediatric Trauma.

BACKGROUND: Intubation in the early postinjury phase can be a high-risk procedure associated with an increased risk of mortality when delayed. Nonroutine events (NREs) are workflow disruptions that can be latent safety threats in high-risk settings and may contribute to adverse outcomes. MATERIALS AND METHODS: We reviewed videos of intubations of injured children (age<17 y old) in the emergency department occurring between 2014 and 2018 to identify NREs occurring between the decision to intubate and successful intubation ("critical window"). RESULTS: Among 34 children requiring intubation, the indications included GCS≤8 (n = 20, 58.8%), cardiac arrest (n = 6, 17.6%), airway protection (n = 5, 14.7%), and respiratory failure (n = 3, 8.8%). The median duration of the "critical window" was 7.5 min (range 1.4-27.5 min), with a median of six NREs per case in this period (range 2-30). Most NREs (n = 159, 61.9%) delayed workflow, with 31 (12.1%) of these delays each lasting more than one minute. Eighty-seven NREs (33.9%) had a potential for harm but did not lead to direct patient harm. The most common NREs directly related to the intubation process were poor positioning for intubation (n = 23, 8.9%) and difficulty passing the endotracheal tube (n = 5, 1.9%), with most being attributed to the anesthesiologist performing the intubation (n = 51, range 0-7). CONCLUSIONS: Workflow disruptions related to nonroutine events were frequent during pediatric trauma intubation and were often associated with delays and potential for patient harm. Interventions for improving the efficiency and timeliness of the critical window should focus on adherence to intubation protocol and improving communication and teamwork related to tasks in this phase.

Pediatric Treadmill Friction Burns to the Hand: Outcomes of an Initial Nonoperative Approach.

Treadmill burns that occur from friction mechanism are a common cause of hand burns in children. These burns are deeper and more likely to require surgical intervention compared to hand burns from other mechanisms. The purpose of this study was to identify the factors associated with healing time using an initial nonoperative approach. A retrospective chart review was performed examining children (<15 years) who were treated for treadmill burns to the hand between 2012 and 2019. Patient age, burn depth, total body surface area of the hand injury, and time to healing were recorded. Topical wound management strategies (silver sheet, silver cream, non-silver sheet, and non-silver cream) and associated treatment durations were determined. For patients with burns to bilateral hands, the features, treatment, and outcomes of each hand were assessed separately. Cox regression analysis was used to evaluate the association between time to healing and patient characteristics and treatment type. Seventy-seven patients with 86 hand burns (median age 3 years, range 1-11) had a median total body surface area per hand burn of 0.8% (range 0.1-1.5%). Full-thickness burns (n = 47, 54.7%) were associated with longer time to healing compared to partial-thickness burns (HR 0.28, CI 0.15-0.54, P < .001). Silver sheet treatment was also associated with more rapid time to healing compared to treatment with a silver cream (HR 2.64, CI 1.01-6.89, P = .047). Most pediatric treadmill burns can be managed successfully with a nonoperative approach. More research is needed to confirm the superiority of treatment with silver sheets compared to treatment with silver creams.

Checklist Design Reconsidered: Understanding Checklist Compliance and Timing of Interactions.

We examine the association between user interactions with a checklist and task performance in a time-critical medical setting. By comparing 98 logs from a digital checklist for trauma resuscitation with activity logs generated by video review, we identified three non-compliant checklist use behaviors: failure to check items for completed tasks, falsely checking items when tasks were not performed, and inaccurately checking items for incomplete tasks. Using video review, we found that user perceptions of task completion were often misaligned with clinical practices that guided activity coding, thereby contributing to non-compliant check-offs. Our analysis of associations between different contexts and the timing of check-offs showed longer delays when (1) checklist users were absent during patient arrival, (2) patients had penetrating injuries, and (3) resuscitations were assigned to the highest acuity. We discuss opportunities for reconsidering checklist designs to reduce non-compliant checklist use.

Comparing the Effects of Paper and Digital Checklists on Team Performance in Time-Critical Work.

This mixed-methods study examines the effects of a tablet-based checklist system on team performance during a dynamic and safety-critical process of trauma resuscitation. We compared team performance from 47 resuscitations that used a paper checklist to that from 47 cases with a digital checklist to determine if digitizing a checklist led to improvements in task completion rates and in how fast the tasks were initiated for 18 most critical assessment and treatment tasks. We also compared if the checklist compliance increased with the digital design. We found that using the digital checklist led to more frequent completions of the initial airway assessment task but fewer completions of ear and lower extremities exams. We did not observe any significant differences in time to task performance, but found increased compliance with the checklist. Although improvements in team performance with the digital checklist were minor, our findings are important because they showed no adverse effects as a result of the digital checklist introduction. We conclude by discussing the takeaways and implications of these results for effective digitization of medical work.

Process conformance is associated with successful first intubation attempt and lower odds of adverse events in a paediatric emergency setting.

BACKGROUND: Intubation is an essential, life-saving skill but associated with a high risk for adverse outcomes. Intubation protocols have been implemented to increase success and reduce complications, but the impact of protocol conformance is not known. Our study aimed to determine association between conformance with an intubation process model and outcomes. METHODS: An interdisciplinary expert panel developed a process model of tasks and sequencing deemed necessary for successful intubation. The model was then retrospectively used to review videos of intubations from 1 February, 2014, to 31 January, 2016, in a paediatric emergency department at a time when no process model or protocol was in existence. RESULTS: We evaluated 113 patients, 77 (68%) were successfully intubated on first attempt. Model conformance was associated with a higher likelihood of first attempt success when using direct laryngoscopy (OR 1.09, 95% CI 1.01 to 1.18). The use of video laryngoscopy was associated with an overall higher likelihood of success on first attempt (OR 2.54, 95% CI 1.10 to 5.88). Thirty-seven patients (33%) experienced adverse events. Model conformance was the only factor associated with a lower odds of adverse events (OR 0.94, 95% CI 0.88 to 0.99). CONCLUSIONS: Conformance with a task-based expert-derived process model for emergency intubation was associated with a higher rate of success on first intubation attempt when using direct laryngoscopy and a lower odds of associated adverse events. Further evaluation of the impact of human factors, such as teamwork and decision-making, on intubation process conformance and success and outcomes is needed.

Multimodal Attention Network for Trauma Activity Recognition from Spoken Language and Environmental Sound.

Trauma activity recognition aims to detect, recognize, and predict the activities (or tasks) during a trauma resuscitation. Previous work has mainly focused on using various sensor data including image, RFID, and vital signals to generate the trauma event log. However, spoken language and environmental sound, which contain rich communication and contextual information necessary for trauma team cooperation, are still largely ignored. In this paper, we propose a multimodal attention network (MAN) that uses both verbal transcripts and environmental audio stream as input; the model extracts textual and acoustic features using a multi-level multi-head attention module, and forms a final shared representation for trauma activity classification. We evaluated the proposed architecture on 75 actual trauma resuscitation cases collected from a hospital. We achieved 72.4% accuracy with 0.705 F1 score, demonstrating that our proposed architecture is useful and efficient. These results also show that using spoken language and environmental audio indeed helps identify hard-to-recognize activities, compared to previous approaches. We also provide a detailed analysis of the performance and generalization of the proposed multimodal attention network.

The Establishment of a Lung Colonization Assay for Circulating Tumor Cell Visualization in Lung Tissues.

Metastasis is the major cause of cancer death. The role of circulating tumor cells (CTCs) in promoting cancer metastasis, in which lung colonization by CTCs critically contributes to early lung metastatic processes, has been vigorously investigated. As such, animal models are the only approach that captures the full systemic process of metastasis. Given that problems occur in previous experimental designs for examining the contributions of CTCs to blood vessel extravasation, we established an in vivo lung colonization assay in which a long-term-fluorescence cell-tracer, carboxyfluorescein succinimidyl ester (CFSE), was used to label suspended tumor cells and lung perfusion was performed to clear non-specifically trapped CTCs prior to lung removal, confocal imaging, and quantification. Polymeric fibronectin (polyFN) assembled on CTC surfaces has been found to mediate lung colonization in the final establishment of metastatic tumor tissues. Here, to specifically test the requirement of polyFN assembly on CTCs for lung colonization and extravasation, we performed short term lung colonization assays in which suspended Lewis lung carcinoma cells (LLCs) stably expressing FN-shRNA (shFN) or scramble-shRNA (shScr) and pre-labeled with 20 µM of CFSE were intravenously inoculated into C57BL/6 mice. We successfully demonstrated that the abilities of shFN LLC cells to colonize the mouse lungs were significantly diminished in comparison to shScr LLC cells. Therefore, this short-term methodology may be widely applied to specifically demonstrate the ability of CTCs within the circulation to colonize the lungs.