Influence of health insurance on withdrawal of life sustaining treatment for patients with isolated traumatic brain injury: a retrospective multi-center observational cohort study.

BACKGROUND: Healthcare inequities for patients with traumatic brain injury (TBI) represent a major priority area for trauma quality improvement. We hypothesized a relationship between health insurance status and timing of withdrawal of life sustaining treatment (WLST) for adults with severe TBI. METHODS: This multicenter retrospective observational cohort study utilized data collected between 2017 and 2020. We identified adult (age ≥ 16) patients with isolated severe TBI admitted participating Trauma Quality Improvement Program centers. We determined the relationship between insurance status (public, private, and uninsured) and the timing of WLST using a competing risk survival analysis framework adjusting for baseline, clinical, injury and trauma center characteristics. Multivariable cause-specific Cox regressions were used to compute adjusted hazard ratios (HR) reflecting timing of WLST, accounting for mortality events. We also quantified the between-center residual variability in WLST using the median odds ratio (MOR) and measured insurance status association with access to rehabilitation at discharge. RESULTS: We identified 42,111 adults with isolated severe TBI treated across 509 trauma centers across North America. There were 10,771 (25.6%) WLST events in the cohort and a higher unadjusted incidence of WLST events was evident in public insurance patients compared to private or uninsured groups. After adjustment, WLST occurred earlier for publicly insured (HR 1.07, 95% CI 1.02-1.12) and uninsured patients (HR 1.29, 95% CI 1.18-1.41) compared to privately insured patients. Access to rehabilitation was lower for both publicly insured and uninsured patients compared to patients with private insurance. Accounting for case-mix, the MOR was 1.49 (95% CI 1.43-1.55), reflecting significant residual between-center variation in WLST decision-making. CONCLUSIONS: Our findings highlight the presence of disparate WLST practices independently associated with health insurance status. Additionally, these results emphasize between-center variability in WLST, persisting despite adjustments for measurable patient and trauma center characteristics.

Factors influencing withdrawal of life-supporting treatment in cervical spinal cord injury: a large multicenter observational cohort study.

BACKGROUND: Traumatic spinal cord injury (SCI) leads to profound neurologic sequelae, and the provision of life-supporting treatment serves great importance among this patient population. The decision for withdrawal of life-supporting treatment (WLST) in complete traumatic SCI is complex with the lack of guidelines and limited understanding of practice patterns. We aimed to evaluate the individual and contextual factors associated with the decision for WLST and assess between-center differences in practice patterns across North American trauma centers for patients with complete cervical SCI. METHODS: This retrospective multicenter observational cohort study utilized data derived from the American College of Surgeons Trauma Quality Improvement Program database between 2017 and 2020. The study included adult patients (> 16 years) with complete cervical SCI. We constructed a multilevel mixed effect logistic regression model to adjust for patient, injury and hospital factors influencing WLST. Factors associated with WLST were estimated through odds ratios with 95% confidence intervals. Hospital variability was characterized using the median odds ratio. Unexplained residual variability was assessed through the proportional change in variation between models. RESULTS: We identified 5070 patients with complete cervical SCI treated across 477 hospitals, of which 960 (18.9%) had WLST. Patient-level factors associated with significantly increased likelihood of WLST were advanced age, male sex, white race, prior dementia, low presenting Glasgow Coma Scale score, having a pre-hospital cardiac arrest, SCI level of C3 or above, and concurrent severe injury to the head or thorax. Patient-level factors associated with significantly decreased likelihood of WLST included being racially Black or Asian. There was significant variability across hospitals in the likelihood for WLST while accounting for case-mix, hospital size, and teaching status (MOR 1.51 95% CI 1.22-1.75). CONCLUSIONS: A notable proportion of patients with complete cervical SCI undergo WLST during their in-hospital admission. We have highlighted several factors associated with this decision and identified considerable variability between hospitals. Further work to standardize WLST guidelines may improve equity of care provided to this patient population.

Key role of the ryanodine receptor I4790K mutation in mediating diamide resistance in Plutella xylostella.

The diamondback moth Plutella xylostella, a global insect pest of cruciferous vegetables, has evolved resistance to many classes of insecticides including diamides. Three point mutations (I4790M, I4790K, and G4946E) in the ryanodine receptor of P. xylostella (PxRyR) have been identified to associate with varying levels of resistance. In this study, we generated a knockin strain (I4790K-KI) of P. xylostella, using CRISPR/Cas9 to introduce the I4790K mutation into PxRyR of the susceptible IPP-S strain. Compared to IPP-S, the edited I4790K-KI strain exhibited high levels of resistance to both anthranilic diamides (chlorantraniliprole 1857-fold, cyantraniliprole 1433-fold) and the phthalic acid diamide flubendiamide (>2272-fold). Resistance to chlorantraniliprole in the I4790K-KI strain was inherited in an autosomal and recessive mode, and genetically linked with the I4790K knockin mutation. Computational modeling suggests the I4790K mutation reduces the binding of diamides to PxRyR by disrupting key hydrogen bonding interactions within the binding cavity. The approximate frequencies of the 4790M, 4790K, and 4946E alleles were assessed in ten geographical field populations of P. xylostella collected in China in 2021. The levels of chlorantraniliprole resistance (2.3- to 1444-fold) in these populations were significantly correlated with the frequencies (0.017-0.917) of the 4790K allele, but not with either 4790M (0-0.183) or 4946E (0.017-0.450) alleles. This demonstrates that the PxRyR I4790K mutation is currently the major contributing factor to chlorantraniliprole resistance in P. xylostella field populations within China. Our findings provide in vivo functional evidence for the causality of the I4790K mutation in PxRyR with high levels of diamide resistance in P. xylostella, and suggest that tracking the frequency of the I4790K allele is crucial for optimizing the monitoring and management of diamide resistance in this crop pest.

Admitting Hospital Influences on Withdrawal of Life-Sustaining Treatment Decision for Patients With Severe Traumatic Brain Injury.

BACKGROUND AND OBJECTIVES: Withdrawal of life-sustaining treatment (WLST) in severe traumatic brain injury (TBI) is complex, with a paucity of standardized guidelines. We aimed to assess the variability in WLST practices between trauma centers in North America. METHODS: This retrospective study used data from trauma centers through the American College of Surgeons Trauma Quality Improvement Program between 2017 and 2020. We included adult patients (>16 years) with severe TBI and a documented decision for WLST. We constructed a series of hierarchical logistic regression models to adjust for patient, injury, and hospital attributes influencing WLST; residual between-center variability was characterized using the median odds ratio. The impact of disparate WLST practices was further assessed by ranking centers by their conditional random intercept and assessing mortality, length of stay, and WLST between quartiles. RESULTS: We identified a total of 85 511 subjects with severe TBI treated across 510 trauma centers, of whom 20 300 (24%) had WLST. Patient-level factors associated with increased likelihood of WLST were advanced age, White race, self-pay, or Medicare insurance status (compared with private insurance). Black race was associated with reduced tendency for WLST. Treatment in nonprofit centers and higher-severity intracranial and extracranial injuries, midline shift, and pupil asymmetry also increased the likelihood for WLST. After adjustment for patient and hospital attributes, the median odds ratio was 1.45 (1.41-1.49 95% CI), suggesting residual variation in WLST between centers. When centers were grouped into quartiles by their propensity for WLST, there was increased adjusted mortality and shorter length of stay in fourth compared with first quartile centers. CONCLUSION: We highlighted the presence of contextual phenomena associated with disparate WLST practice patterns between trauma centers after adjustment for case-mix and hospital attributes. These findings highlight a need for standardized WLST guidelines to improve equity of care provision for patients with severe TBI.

Contemporary trends in the incidence and timing of spinal metastases: A population-based study.

Background: Spinal metastases are a significant complication of advanced cancer. In this study, we assess temporal trends in the incidence and timing of spinal metastases and examine underlying patient demographics and primary cancer associations. Methods: In this population-based retrospective cohort study, health data from 2007 to 2019 in Ontario, Canada were analyzed (n = 37, 375 patients identified with spine metastases). Primary outcomes were annual incidence of spinal metastasis, and time to metastasis after primary diagnosis. Results: The age-standardized incidence of spinal metastases increased from 229 to 302 cases per million over the 13-year study period. The average annual percent change (AAPC) in incidence was 2.2% (95% CI: 1.4% to 3.0%) with patients aged ≥85 years demonstrating the largest increase (AAPC 5.2%; 95% CI: 2.3% to 8.3%). Lung cancer had the greatest annual incidence, while prostate cancer had the greatest increase in annual incidence (AAPC 6.5; 95% CI: 4.1% to 9.0%). Lung cancer patients were found to have the highest risk of spine metastasis with 10.3% (95% CI: 10.1% to 10.5%) of patients being diagnosed at 10 years. Gastrointestinal cancer patients were found to have the lowest risk of spine metastasis with 1.0% (95% CI: 0.9% to 1.0%) of patients being diagnosed at 10 years. Conclusions: The incidence of spinal metastases has increased in recent years, particularly among older patients. The incidence and timing vary substantially among different primary cancer types. These findings contribute to the understanding of disease trends and emphasize a growing population of patients who require subspecialty care.

Quantifying the Association Between Surgical Spine Approach and Tracheostomy Timing After Traumatic Cervical Spinal Cord Injury.

BACKGROUND AND OBJECTIVES: Recent evidence suggests earlier tracheostomy is associated with fewer complications in patients with complete cervical spinal cord injury (SCI). This study aims to evaluate the influence of spine surgical approach on the association between tracheostomy timing and in-hospital adverse events treating patients with complete cervical SCI. METHODS: This retrospective cohort study was performed using Trauma Quality Improvement Program data from 2017 to 2020. All patients with acute complete (American Spinal Injury Association-A) cervical SCI who underwent tracheostomy and spine surgery were included. Tracheostomy timing was dichotomized to early (within 1 week after surgery) and delayed (more than 1 week after surgery). Primary outcome was the occurrence of major in-hospital complications. Secondary outcomes included occurrences of immobility-related complications, surgical-site infection, hospital and intensive care unit length of stay, and time on mechanical ventilation. RESULTS: The study included 1592 patients across 358 trauma centers. Mean time to tracheostomy from surgery was 8.6 days. A total of 495 patients underwent anterior approach, 670 underwent posterior approach, and 427 underwent combined anterior and posterior approach. Patients who underwent anterior approach were significantly more likely to have delayed tracheostomy compared with posterior approach (53% vs 40%, P < .001). Early tracheotomy significantly reduced major in-hospital complications (odds ratio 0.67, 95% CI 0.53-0.84) and immobility complications (odds ratio = 0.78, 95% CI 0.6-1.0). Those undergoing early tracheostomy spent 6.0 (95% CI -8.47 to -3.43) fewer days in hospital, 5.7 (95% CI -7.8 to -3.7) fewer days in the intensive care unit, and 5.9 (95% CI -8.2 to -3.7) fewer days ventilated. Surgical approach had no significant negative effect on the association between tracheostomy timing and the outcomes of interest. CONCLUSION: Earlier tracheostomy for patients with cervical SCI is associated with reduced complications, length of stay, and ventilation time. This relationship appears independent of the surgical approach. These findings emphasize that tracheostomy need not be delayed because of the SCI treatment approach.

Vision Transformer-based Decision Support for Neurosurgical Intervention in Acute Traumatic Brain Injury: Automated Surgical Intervention Support Tool.

Purpose To develop an automated triage tool to predict neurosurgical intervention for patients with traumatic brain injury (TBI). Materials and Methods A provincial trauma registry was reviewed to retrospectively identify patients with TBI from 2005 to 2022 treated at a specialized Canadian trauma center. Model training, validation, and testing were performed using head CT scans with binary reference standard patient-level labels corresponding to whether the patient received neurosurgical intervention. Performance and accuracy of the model, the Automated Surgical Intervention Support Tool for TBI (ASIST-TBI), were also assessed using a held-out consecutive test set of all patients with TBI presenting to the center between March 2021 and September 2022. Results Head CT scans from 2806 patients with TBI (mean age, 57 years ± 22 [SD]; 1955 [70%] men) were acquired between 2005 and 2021 and used for training, validation, and testing. Consecutive scans from an additional 612 patients (mean age, 61 years ± 22; 443 [72%] men) were used to assess the performance of ASIST-TBI. There was accurate prediction of neurosurgical intervention with an area under the receiver operating characteristic curve (AUC) of 0.92 (95% CI: 0.88, 0.94), accuracy of 87% (491 of 562), sensitivity of 87% (196 of 225), and specificity of 88% (295 of 337) on the test dataset. Performance on the held-out test dataset remained robust with an AUC of 0.89 (95% CI: 0.85, 0.91), accuracy of 84% (517 of 612), sensitivity of 85% (199 of 235), and specificity of 84% (318 of 377). Conclusion A novel deep learning model was developed that could accurately predict the requirement for neurosurgical intervention using acute TBI CT scans. Keywords: CT, Brain/Brain Stem, Surgery, Trauma, Prognosis, Classification, Application Domain, Traumatic Brain Injury, Triage, Machine Learning, Decision Support Supplemental material is available for this article. © RSNA, 2024 See also commentary by Haller in this issue.

Insurance-Related Disparities in Withdrawal of Life Support and Mortality After Spinal Cord Injury.

Importance: Identifying disparities in health outcomes related to modifiable patient factors can improve patient care. Objective: To compare likelihood of withdrawal of life-supporting treatment (WLST) and mortality in patients with complete cervical spinal cord injury (SCI) with different types of insurance. Design, Setting, and Participants: This retrospective cohort study collected data between 2013 and 2020 from 498 trauma centers participating in the Trauma Quality Improvement Program. Participants included adult patients (older than 16 years) with complete cervical SCI. Data were analyzed from November 1, 2023, through May 18, 2024. Exposure: Uninsured or public insurance compared with private insurance. Main Outcomes and Measures: Coprimary outcomes were WLST and mortality. The adjusted odds ratio (aOR) of each outcome was estimated using hierarchical logistic regression. Propensity score matching was used as an alternative analysis to compare public and privately insured patients. Process of care outcomes, including the occurrence of a hospital complication and length of stay, were compared between matched patients. Results: The study included 8421 patients with complete cervical SCI treated across 498 trauma centers (mean [SD] age, 49.1 [20.2] years; 6742 male [80.1%]). Among the 3524 patients with private insurance, 503 had WLST (14.3%) and 756 died (21.5%). Among the 3957 patients with public insurance, 906 had WLST (22.2%) and 1209 died (30.6%). Among the 940 uninsured patients, 156 had WLST (16.6%) and 318 died (33.8%). A significant difference was found between uninsured and privately insured patients in the adjusted odds of WLST (aOR, 1.49; 95% CI, 1.11-2.01) and mortality (aOR, 1.98; 95% CI, 1.50-2.60). Similar results were found in subgroup analyses. Matched public compared with private insurance patients were found to have significantly greater odds of hospital complications (odds ratio, 1.27; 95% CI, 1.14-1.42) and longer hospital stay (mean difference 5.90 days; 95% CI, 4.64-7.20), which was redemonstrated on subgroup analyses. Conclusions and Relevance: Health insurance type was associated with significant differences in the odds of WLST, mortality, hospital complications, and days in hospital among patients with complete cervical SCI in this study. Future work is needed to incorporate patient perspectives and identify strategies to close the quality gap for the large number of patients without private insurance.

Development of the cervical myelopathy severity index: a new patient reported outcome measure to quantify impairments and functional limitations.

BACKGROUND CONTEXT: Existing degenerative cervical myelopathy (DCM) severity scales have significant shortcomings, creating a strong impetus for the development of a practical measurement tool with sound psychometric properties. PURPOSE: This work reports the item generation and reduction of the Cervical Myelopathy Severity Index (CMSI), a new DCM patient-reported outcome measure of symptoms and functional limitations. DESIGN: Prospective observational study. PATIENT SAMPLE: Adult DCM patients belonging to one of three distinct treatment groups: (1) observation cohort, (2) preoperative surgical cohort, (3) 6 to 12 months postoperative cohort. OUTCOME MEASURES: Patient-reported outcome measure of symptoms and functional limitations. METHODS: Item generation was performed using semi-structured patient focus groups emphasizing symptoms experienced and functional limitations. Readability was assessed through think-aloud patient interviews. Item reduction involved surveys of DCM patients with a spectrum of disease severity and board-certified spine surgeons experienced in the treatment of DCM. A priori criteria for item removal included: patient median importance/severity <2 (of 4), 30% or more no severity (response of zero), item severity correlations ≤ 0.80 (Spearman), item severity reliability (weighted kappa <0.60) based on a 2-week interval and clinician median importance <2 with retention of items with very high clinical importance. RESULTS: There were 42 items generated from a combination of specialist input and patient focus groups. Items captured sensorimotor symptoms and limitations related to upper and lower extremities as well as sphincter dysfunction. Ninety-eight patients (43, 30, 25 observation, pre- and postsurgery respectively) and 51 surgeons completed the assessment. Twenty-three items remained after application of median importance and severity thresholds and weighted kappa cutoffs. After elimination of highly correlated (>0.80) items and combining two similar items, the final CMSI questionnaire list included 14 items. CONCLUSIONS: The CMSI is a new DCM patient-reported clinical measurement tool developed using patient and clinician input to inform item generation and reduction. Future work will evaluate the reliability, validity, and responsiveness of the CMSI in relation to existing myelopathy measurement indices.

The Mediating Roles of Future Work Self and Hope on the Association Between Perceived Social Support and Depressive Symptoms Among Chinese Vocational School Students: A Cross-Sectional Study.

Purpose: Depressive symptoms are serious mental health problems, which are harmful for adolescents' physical and psychological development. Limited studies have focused on depressive symptoms of vocational high school students, who are more susceptible to mental health problems than high school students. Based on the main effect model of social support and self-regulation theory, the current study aims at exploring two potential mediating roles of hope and future work self on the relationship between perceived social support and depressive symptoms among vocational high school students by a cross-sectional study. Participants and Methods: A total of 521 vocational high school students aged 14-21 (M= 16.45; SD= 0.91) participated in the survey. There were 266 males (51.1%) and 255 females (48.9%). The multidimensional scale of perceived social support, the future work self scale, the children's hope scale, and the center for epidemiologic studies depression scale were applied in the study. Results: The results revealed that: (1) perceived social support, future work self, and hope were negatively related to depressive symptoms (r = -0.25 to -0.35, p < 0.001); (2) students who perceived more social support have fewer depressive symptoms (ß = -0.22, p < 0.001); (3) perceived social support predicted a more salient future work self and then was associated with higher levels of hope, which in turn, was related to lower levels of depressive symptoms (ß = -0.02, and 95% CI = [-0.035, -0.005]). Conclusion: Perceived social support was the protective factor against vocational school students' depressive symptoms. More specifically, stronger perceived social support predicted a more salient future work self, which promoted high level of hope, and ultimately decreased vocational school students' depressive symptoms. The findings provide enlighten implications for interventions on depressive symptoms among vocational high school students.

Metabolic functional redundancy of the CYP9A subfamily members leads to P450-mediated lambda-cyhalothrin resistance in Cydia pomonella.

BACKGROUND: The evolution of insect resistance to pesticides poses a continuing threat to sustainable pest management. While much is known about the molecular mechanisms that confer resistance in model insects and few agricultural pests, far less is known about fruit pests. Field-evolved resistance to synthetic insecticides such as lambda-cyhalothrin has been widely documented in Cydia pomonella, a major invasive pest of pome fruit worldwide, and the increased production of cytochrome P450 monooxygenases (P450s) has been linked to resistance in field-evolved resistant populations. However, the underlying molecular mechanisms of P450-mediated insecticide resistance remain largely unknown. RESULTS: Here we found that functional redundancy and preference of metabolism by P450s genes in the CYP9A subfamily confer resistance to lambda-cyhalothrin in Cydia pomonella. A total of four CYP9A genes, including CYP9A61, CYP9A120, CYP9A121, and CYP9A122, were identified from Cydia pomonella. Among these, CYP9A120, CYP9A121, and CYP9A122 were predominantly expressed in the midgut of larvae. The expression levels of these P450 genes were significantly induced by a lethal dose that would kill 10% (LD10 ) of lambda-cyhalothrin and were overexpressed in a field-evolved lambda-cyhalothrin resistant population. Knockdown of CYP9A120 and CYP9A121 by RNA-mediated interference (RNAi) increased the susceptibility of larvae to lambda-cyhalothrin. In vitro assays demonstrated that recombinant P450s expressed in Sf9 cells can metabolize lambda-cyhalothrin, but with functional redundancy and divergence through regioselectivity of metabolism. CYP9A121 preferred to convert lambda-cyhalothrin to 2'-hydroxy-lambda-cyhalothrin, whereas CYP9A122 only generated 4'-hydroxy metabolite of lambda-cyhalothrin. Although possesses a relatively low metabolic capability, CYP9A120 balanced catalytic competence to generate both 2'- and 4'-metabolites. CONCLUSION: Collectively, these results reveal that metabolic functional redundancy of three members of the CYP9A subfamily leads to P450-mediated lambda-cyhalothrin resistance in Cydia pomonella, thus representing a potential adaptive evolutionary strategy during its worldwide expansion. © 2022 Society of Chemical Industry.

Analysis of recovery trajectories in degenerative cervical myelopathy to facilitate improved patient counseling and individualized treatment recommendations.

OBJECTIVE: There is a need to better understand and predict postsurgical outcomes for degenerative cervical myelopathy (DCM) patients, particularly to support treatment decisions for patients with mild DCM. The goal of this study was to identify and predict outcome trajectories for DCM patients up to 2 years postsurgery. METHODS: The authors analyzed two North American multicenter prospective DCM studies (n = 757). Functional recovery and physical health component quality of life were assessed in DCM patients at baseline, 6 months, and 1 and 2 years postoperatively using the modified Japanese Orthopaedic Association (mJOA) score and Physical Component Summary (PCS) of the SF-36, respectively. Group-based trajectory modeling was used to identify recovery trajectories for mild, moderate, and severe DCM. Prediction models for recovery trajectories were developed and validated in bootstrap resamples. RESULTS: Two recovery trajectories were identified for the functional and physical components of quality of life: good recovery and marginal recovery. Depending on outcome and myelopathy severity, one-half to three-fourths of the study patients followed the good recovery trajectory characterized by improvement in mJOA and PCS scores over time. The remaining one-half to one-fourth of patients followed the marginal recovery trajectory, experiencing little improvement and, in certain cases, worsening postoperatively. The prediction model for mild DCM had an area under the curve of 0.72 (95% CI 0.65-0.80), with preoperative neck pain, smoking, and posterior surgical approach noted as dominant predictors of marginal recovery. CONCLUSIONS: Surgically treated DCM patients follow distinct recovery trajectories in the first 2 years postoperatively. While most patients experience substantial improvement, a significant minority experience little improvement or worsening. The ability to predict DCM patient recovery trajectories in the preoperative setting facilitates the formulation of individualized treatment recommendations for patients with mild symptoms.

Multicenter retrospective cohort study of the association between surgery for odontoid fractures in the elderly and in-hospital outcomes.

Odontoid fractures are increasingly prevalent in older adults and associated with high morbidity and mortality. Optimal management remains controversial. Our study aims to investigate the association between surgical management of odontoid fractures and in-hospital mortality in a multi-center geriatric cohort. We identified patients 65 years or older with C2 odontoid fractures from the Trauma Quality Improvement Program database. The primary study outcome was in-hospital mortality. Secondary outcomes were in-hospital complications and hospital length of stay. Generalized estimating equation models were used to compare outcomes between operative and non-operative cohorts. Among the 13,218 eligible patients, 1100 (8.3%) were treated surgically. The risk of in-hospital mortality did not differ between surgical and non-surgical groups, after patient and hospital-level adjustment (OR: 0.94, 95%CI: 0.55-1.60). The risks of major complications and immobility-related complications were higher in the operative cohort (adjusted OR: 2.12, 95%CI: 1.53-2.94; and OR: 2.24, 95%CI: 1.38-3.63, respectively). Patients undergoing surgery had extended in-hospital length of stay compared to the non-operative group (9 days, IQR: 6-12 days vs. 4 days, IQR: 3-7 days). These findings were supported by secondary analyses that considered between-center differences in rates of surgery. Among geriatric patients with odontoid fractures surgical management was associated with similar in-hospital mortality, but higher in-hospital complication rates compared to non-operative management. Surgical management of geriatric patients with odontoid fractures requires careful patient selection and consideration of pre-existing comorbidities.

Earlier Tracheostomy Reduces Complications in Complete Cervical Spinal Cord Injury in Real-World Practice: Analysis of a Multicenter Cohort of 2001 Patients.

BACKGROUND AND OBJECTIVES: It is believed that early tracheostomy in patients with traumatic cervical spinal cord injury (SCI) may lessen the risk of developing complications and reduce the duration of mechanical ventilation and critical care stay. This study aims to assess whether early tracheostomy is beneficial in patients with traumatic cervical SCI. METHODS: We conducted a retrospective cohort study using data from the American College of Surgeons Trauma Quality Improvement Program database from 2010 to 2018. Adult patients with a diagnosis of acute complete (ASIA A) traumatic cervical SCI who underwent surgery and tracheostomy were included. Patients were stratified into those receiving early (at or before 7 days) and delayed tracheostomy. Propensity score matching was used to assess the association between delayed tracheostomy and the risk of in-hospital adverse events. Risk-adjusted variability in tracheostomy timing across trauma centers was investigated using mixed-effects regression. RESULTS: The study included 2001 patients from 374 North American trauma centers. The median time to tracheostomy was 9.2 days (IQR: 6.1-13.1 days), with 654 patients (32.7%) undergoing early tracheostomy. After matching, the odds of a major complication were significantly lower for early tracheostomy patients (OR: .90; 95% CI: .88-.98). Patients were also significantly less likely to experience an immobility-related complication (OR: .90; 95% CI: .88-.98). Patients in the early group spent 8.2 fewer days in the critical care unit (95% CI: -10.2 to -6.61) and 6.7 fewer days ventilated (95% CI: -9.44 to -5.23). There was significant variability in tracheostomy timeliness between trauma centers with a median odds ratio of 12.2 (95% CI: 9.7-13.7), which was not explained by case-mix and hospital-level characteristics. CONCLUSION: A 7-day threshold to implement tracheostomy seems to be associated with reduced in-hospital complications, time in the critical care unit, and time on mechanical ventilation.

Involvement of CYP2 and mitochondrial clan P450s of Helicoverpa armigera in xenobiotic metabolism.

Insect CYP2 and mitochondrial clan P450s are relatively conserved genes encoding enzymes generally thought to be involved in biosynthesis or metabolism of endobiotics. However, emerging evidence argues they have potential roles in chemical defense as well, but their actual detoxification functions remain largely unknown. Here, we focused on the full complement of 8 CYP2 and 10 mitochondrial P450s in the generalist herbivore, Helicoverpa armigera. Their varied spatiotemporal expression profiles were analyzed and reflected their specific functions. For functional study of the mitochondrial clan P450s, the redox partners, adrenodoxin reductase (AdR) and adrenodoxin (Adx), were identified from genomes of eight insects and an efficient in vitro electron transfer system of mitochondrial P450 was established by co-expression with Adx and AdR of H. armigera. All CYP2 clan P450s and 8 mitochondrial P450s were successfully expressed in Sf9 cells and compared functionally. In vitro metabolism assays showed that two CYP2 clan P450s (CYP305B1 and CYP18A1) and CYP333B3 (mito clan) could epoxidize aldrin to dieldrin, while CYP305B1 and CYP339A1 (mito clan) have limited but significant hydroxylation capacities to esfenvalerate. CYP303A1 of the CYP2 clan exhibits high metabolic efficiency to 2-tridecanone. Screening the xenobiotic metabolism competence of CYP2 and mitochondrial clan P450s not only provides new insights on insect chemical defense but also can give indications on their physiological functions in H. armigera and other insects.

The Difference in Learning Activities of Postgraduate Students of Different Qualification Types Under the COVID-19 Pandemic: A Multi-Group Latent Class Analysis.

Introduction: There are two types of master's qualifications in China. One is the academic qualification that pays more attention to academic research, aiming to cultivate research-oriented talents; while the other is the application-oriented qualification that focuses more on practical ability, aiming to cultivate applied-oriented talents. The purpose of this study is to explore the impact of the COVID-19 on the learning activities of postgraduate students, as well as the differences in the extent to which the learning activities of postgraduate students of different qualification types are affected and their mental health status. Methods: A self-constructed scale for the pandemic's impact on master's students, the self-rating anxiety scale and the self-rating depression scale were applied in the study. The single- and multi-group latent class analyses were used to investigate the impact of the pandemic on postgraduate students of different qualification types. Results: A total of 2818 responses were collected. The single-group latent class analysis identified four classes. The multi-group latent class analysis showed that no absolute homogeneity existed between different groups. In general, the number of academic master's students affected was greater than application-oriented master's students. Application-oriented master's students were more affected by course activities, while academic master's students were more affected by academic and social activities. Results show that individuals more affected had higher levels of anxiety and depression. Compared to course activities, impacts on social activities were more likely to cause anxiety and depression. Discussion: Universities can provide a more flexible way of assistance to different qualification types of postgraduate students. Furthermore, social activities play an important role in the mental health of postgraduate students. Therefore, under the background of normalization of pandemic prevention and control, schools should pay more attention to students' interpersonal communication activities to help relieve students' anxiety, depression, and other negative emotions.

Single amino acid variations drive functional divergence of cytochrome P450s in Helicoverpa species.

Divergence of gene function is a hallmark of evolution, but assessing such divergence in one species or between species requires information on functional alterations of the alleles and homologs. Here, we explore the functional divergence of two paralogs, CYP6AE19 and CYP6AE20, from Helicoverpa armigera, and two close orthologs, CYP6B8 and CYP6B7, from two related species (Helicoverpa zea and H. armigera); although there is high sequence identity within each pair of enzymes, the latter P450 of each pair has lost metabolic competence towards the plant allelochemical xanthotoxin. Multiple chimeric and single/double site mutants were created by exchanging the diverse substrate recognition sites (SRSs) and amino acids within each pair of P450s. Heterologous expression in Sf9 cells and in vitro metabolism studies showed that the exchange of SRS4 swapped the activity of CYP6AE19 and CYP6AE20, and subsequent site-directed mutagenesis demonstrated that the CYP6AE20 V318M substitution causes a gain-of-function towards xanthotoxin. Meanwhile, a single amino acid substitution (L489P) in SRS6 was found to swap activity between the CYP6B orthologs. Sequence alignments of CYP6AE paralogs and all reported insect xanthotoxin-metabolizing P450s suggest M318 and P489 are essential for the catalytic activities of CYP6AE paralogs and CYP6B orthologs, respectively, but P450s in different subfamilies may have different mechanisms towards the same substrate. Our findings demonstrate that a single amino acid substitution can suffice to alter substrate metabolism and this functional divergence resulting from natural mutations will help to further our understanding of the process of natural selection of P450 genes and their role in insect-host plant interactions.