Trim46 knockout impaired neuronal architecture and caused hypoactive behavior in rats.

BACKGROUND: Tripartite motif (TRIM46) is a relatively novel protein that belongs to tripartite motif family. TRIM46 organizes parallel microtubule arrays on the axons, which are important for neuronal polarity and axonal function. TRIM46 is highly expressed in the brain, but its biological function in adults has not yet been determined. RESULTS: Trim46 knockout (KO) rat line was established using CRISPR/cas9. Trim46 KO rats had smaller hippocampus sizes, fewer neuronal dendritic arbors and dendritic spines, and shorter and more distant axon initial segment. Furthermore, the protein interaction between endogenous TRIM46 and FK506 binding protein 5 (FKBP5) in brain tissues was determined; Trim46 KO increased hippocampal FKBP5 protein levels and decreased hippocampal protein kinase B (Akt) phosphorylation, gamma-aminobutyric acid type A receptor subunit alpha1 (GABRA1) and glutamate ionotropic receptor NMDA type subunit 1 (NMDAR1) protein levels. Trim46 KO rats exhibited hypoactive behavioral changes such as reduced spontaneous activity, social interaction, sucrose preference, impaired prepulse inhibition (PPI), and short-term reference memory. CONCLUSIONS: These results demonstrate the significant impact of Trim46 KO on brain structure and behavioral function. This study revealed a novel potential association of TRIM46 with dendritic development and neuropsychiatric behavior, providing new insights into the role of TRIM46 in the brain.

Motor learning changes the axon initial segment of the spinal motoneuron.

We are studying the mechanisms of H-reflex operant conditioning, a simple form of learning. Modelling studies in the literature and our previous data suggested that changes in the axon initial segment (AIS) might contribute. To explore this, we used blinded quantitative histological and immunohistochemical methods to study in adult rats the impact of H-reflex conditioning on the AIS of the spinal motoneuron that produces the reflex. Successful, but not unsuccessful, H-reflex up-conditioning was associated with greater AIS length and distance from soma; greater length correlated with greater H-reflex increase. Modelling studies in the literature suggest that these increases may increase motoneuron excitability, supporting the hypothesis that they may contribute to H-reflex increase. Up-conditioning did not affect AIS ankyrin G (AnkG) immunoreactivity (IR), p-p38 protein kinase IR, or GABAergic terminals. Successful, but not unsuccessful, H-reflex down-conditioning was associated with more GABAergic terminals on the AIS, weaker AnkG-IR, and stronger p-p38-IR. More GABAergic terminals and weaker AnkG-IR correlated with greater H-reflex decrease. These changes might potentially contribute to the positive shift in motoneuron firing threshold underlying H-reflex decrease; they are consistent with modelling suggesting that sodium channel change may be responsible. H-reflex down-conditioning did not affect AIS dimensions. This evidence that AIS plasticity is associated with and might contribute to H-reflex conditioning adds to evidence that motor learning involves both spinal and brain plasticity, and both neuronal and synaptic plasticity. AIS properties of spinal motoneurons are likely to reflect the combined influence of all the motor skills that share these motoneurons. KEY POINTS: Neuronal action potentials normally begin in the axon initial segment (AIS). AIS plasticity affects neuronal excitability in development and disease. Whether it does so in learning is unknown. Operant conditioning of a spinal reflex, a simple learning model, changes the rat spinal motoneuron AIS. Successful, but not unsuccessful, H-reflex up-conditioning is associated with greater AIS length and distance from soma. Successful, but not unsuccessful, down-conditioning is associated with more AIS GABAergic terminals, less ankyrin G, and more p-p38 protein kinase. The associations between AIS plasticity and successful H-reflex conditioning are consistent with those between AIS plasticity and functional changes in development and disease, and with those predicted by modelling studies in the literature. Motor learning changes neurons and synapses in spinal cord and brain. Because spinal motoneurons are the final common pathway for behaviour, their AIS properties probably reflect the combined impact of all the behaviours that use these motoneurons.

Follow-up of women with cervical adenocarcinoma in situ treated by conization: A single centre clinical experience.

OBJECTIVE: Hysterectomy has been the historical gold standard final step in the treatment algorithm of adenocarcinoma in situ (AIS) recommended by most North American colposcopy guidelines. AIS disproportionately affects young childbearing age women, therefore a fertility sparing treatment option is desirable. Our study examines the impact of conservative treatment of AIS with conization followed by serial surveillance. METHODS: A retrospective chart review was completed of patients treated for AIS from 2006 to 2020. Charts were identified by pathologic diagnosis of AIS on cervical and uterine specimens. Charts were excluded if AIS was not treated with conization, if AIS was not confirmed on initial conization specimen, or if invasive disease was found at initial conization. RESULTS: 121 patient charts were analyzed. Median age of patients at first conization and hysterectomy was 34.8 and 40.9, respectively. First conization was by Cold Knife Cone in 58% of patients, and by Loop Electrosurgical Excisional Procedure in 42% of patients. Median follow-up period in our study was 609 days. 5% of patients had recurrence, with only one patient who recurred as cancer. One case of recurrence had a positive initial conization margin. Median time to recurrence was 700 days. 47% of patients underwent eventual hysterectomy. Residual AIS was found in 23% of hysterectomy specimens. Adenocarcinoma was diagnosed on hysterectomy specimen in four patients. CONCLUSION: Our study demonstrates the oncologic safety of treating AIS with conization and serial surveillance. Routine hysterectomy completed as a part of the AIS treatment algorithm, as in current clinical guidelines, is unnecessary.

Calendar-period trends in cervical precancer and cancer diagnoses since the introduction of human papillomavirus and cytology co-testing into routine cervical cancer screening at Kaiser Permanente Northern California.

OBJECTIVES: The longer-term impact of introducing human papillomavirus (HPV) testing into routine cervical cancer screening on precancer and cancer rates by histologic type has not been well described. Calendar trends in diagnoses were examined using data from Kaiser Permanente Northern California, which introduced triennial HPV and cytology co-testing in 2003 for women aged ≥30 years. METHODS: We examined trends in cervical precancer (cervical intraepithelial neoplasia grade 3 [CIN3] and adenocarcinoma in situ [AIS]) and cancer (squamous cell carcinoma [SCC] and adenocarcinoma [ADC]) diagnoses per 1000 screened during 2003-2018. We examined ratios of squamous vs. glandular diagnoses (SCC:ADC and CIN3:AIS). RESULTS: CIN3 and AIS diagnoses increased approximately 2% and 3% annually, respectively (ptrend < 0.001 for both). While SCC diagnoses decreased by 5% per annually (ptrend < 0.001), ADC diagnoses did not change. These patterns were generally observed within each age group (30-39, 40-49, and 50-64 years). ADC diagnoses per 1000 screened did not change even among those who underwent co-testing starting in 2003-2006. SCC:ADC decreased from approximately 2.5:1 in 2003-2006 to 1.3:1 in 2015-2018 while the CIN3:AIS remained relatively constant, ∼10:1. CONCLUSIONS: Since its introduction at KPNC, co-testing increased the detection of CIN3 over time, which likely caused a subsequent reduction of SCC. However, there has been no observed decrease in ADC. One possible explanation for lack of effectiveness against ADC is the underdiagnosis of AIS. Novel strategies to identify and treat women at high risk of ADC need to be developed and clinically validated.

Database Integration Correlates Street Crossing Design Strategies With Pedestrian Injury.

INTRODUCTION: Transportation databases have limited data regarding injury severity of pedestrian versus automobile patients. To identify opportunities to reduce injury severity, transportation and trauma databases were integrated to examine the differences in pedestrian injury severity at street crossings that were signalized crossings (SCs) versus nonsignalized crossings (NSCs). It was hypothesized that trauma database integration would enhance safety analysis and pedestrians struck at NSC would have greater injury severity. METHODS: Single-center retrospective review of all pedestrian versus automobile patients treated at a level 1 trauma center from 2014 to 2018 was performed. Patients were matched to the transportation database by name, gender, and crash date. Google Earth Pro satellite imagery was used to identify SC versus NSC. Injury severity of pedestrians struck at SC was compared to NSC. RESULTS: A total of 512 patients were matched (median age = 41 y [Q1 = 26, Q3 = 55], 74% male). Pedestrians struck at SC (n = 206) had a lower injury severity score (ISS) (median = 9 [4, 14] versus 17 [9, 26], P < 0.001), hospital length of stay (median = 3 [0, 7] versus 6 [1, 15] days, P < 0.001), and mortality (21 [10%] versus 52 [17%], P = 0.04), as compared to those struck at NSC (n = 306). The transportation database had a sensitivity of 63.4% (55.8%-70.4%) and specificity of 63.4% (57.7%-68.9%) for classifying severe injuries (ISS >15). CONCLUSIONS: Pedestrians struck at SC were correlated with a lower ISS and mortality compared to those at NSC. Linkage with the trauma database could increase the transportation database's accuracy of injury severity assessment for nonfatal injuries. Database integration can be used for evidence-based action plans to reduce pedestrian morbidity, such as increasing the number of SC.

The association between lipoprotein(a) levels and ischemic stroke in children: A case-control study.

BACKGROUND: Pediatric arterial ischemic stroke (AIS) is a rare disorder, associated with severe morbidity. In adults, elevated lipoprotein(a) (Lp(a)), a cholesterol-like particle, is associated with ischemic stroke. However, data on Lp(a) and pediatric AIS are scarce. Therefore, we evaluated the association between Lp(a) levels and pediatric AIS. METHODS: We included children who suffered an AIS (≤18 years) and were treated in a tertiary center in Amsterdam, the Netherlands. Two groups of children with AIS were identified: (i) neonates and (ii) children older than 29 days. A case-control study was performed, with the latter group as cases and children without AIS as control group. Cases and controls were matched for age of Lp(a) testing and sex. Multivariable logistic regression models were used. RESULTS: Thirteen neonates and 23 children were included. Mean (SD) age of AIS was 0.6 (2.0) days and 9.2 (6.3) years, respectively. Children with AIS were matched to 62 controls. Lp(a) levels of greater than 50 mg/dL were more prevalent in children with AIS compared to controls (21.7% vs. 3.2%, p = .02). A significant association was found between Lp(a) and AIS (odds ratio [OR] adjusted for age at Lp(a) testing, body mass index [BMI], measurement assay: 1.36 per 10 mg/dL increase of Lp(a), 95% confidence interval [CI]: 1.02-1.82, p = .041). CONCLUSIONS: In this study, Lp(a) levels were positively associated with the risk of AIS in children, suggesting that high Lp(a) might be an independent risk factor for AIS. This underlines the importance of Lp(a) measurement in children with AIS.

Use of bird-borne radar to examine shearwater interactions with legal and illegal fisheries.

Seabirds interact with fishing vessels to consume fishing discards and baits, sometimes resulting in incidental capture (bycatch) and the death of the bird, which has clear conservation implications. To understand seabird-fishery interactions at large spatiotemporal scales, researchers are increasing their use of simultaneous seabird and fishing vessel tracking. However, vessel tracking data can contain gaps due to technical problems, illicit manipulation, or lack of adoption of tracking monitoring systems. These gaps might lead to underestimating the fishing effort and bycatch rates and jeopardize the effectiveness of marine conservation. We deployed bird-borne radar detector tags capable of recording radar signals from vessels. We placed tags on 88 shearwaters (Calonectris diomedea, Calonectris borealis, and Calonectris edwardsii) that forage in the northwestern Mediterranean Sea and the Canary Current Large Marine Ecosystem. We modeled vessel radar detections registered by the tags in relation to gridded automatic identification system (AIS) vessel tracking data to examine the spatiotemporal dynamics of seabird-vessel interactions and identify unreported fishing activity areas. Our models showed a moderate fit (area under the curve >0.7) to vessel tracking data, indicating a strong association of shearwaters to fishing vessels in major fishing grounds. Although in high-marine-traffic regions, radar detections were also driven by nonfishing vessels. The tags registered the presence of potential unregulated and unreported fishing vessels in West African waters, where merchant shipping is unusual but fishing activity is intense. Overall, bird-borne radar detectors showed areas and periods when the association of seabirds with legal and illegal fishing vessels was high. Bird-borne radar detectors could improve the focus of conservation efforts.

Uso de radares en aves para analizar las interacciones de las pardelas con las pesquerías legales e ilegales Resumen Las aves marinas interactúan con los barcos pesqueros para consumir los cebos y lo que descartan, lo que a veces resulta en la captura accesoria y la muerte del ave, por lo que esto tiene implicaciones claras para la conservación. Los investigadores cada vez usan más el rastreo simultáneo de las aves marinas y los barcos pesqueros para comprender las interacciones aves marinas ­ pesquerías a gran escala espaciotemporal. Sin embargo, los datos del rastreo de barcos pueden incluir vacíos por problemas técnicos, manipulación ilícita o porque no adoptan sistemas para monitorear el rastreo. Estos vacíos pueden llevar a subestimar el esfuerzo de pesca y las tasas de captura accesoria y a comprometer la efectividad de la conservación marina. Desplegamos marcas detectoras de radar encima de aves capaces de registrar las señales de radar de los barcos. Colocamos estas marcas en 88 pardelas (Calonectris diomedea, C. borealis, y C. edwardsii) que forrajean en el noroeste del Mar Mediterráneo y el Gran Ecosistema Marino de Canarias. Modelamos las detecciones del radar de los barcos registradas por las marcas en relación con los datos reticulados de rastreo de barcos del sistema de identificación automático (AIS) para analizar las dinámicas espaciotemporales de las interacciones aves marinas­barcos e identificar áreas con actividad pesquera no reportada. Nuestros modelos mostraron un ajuste moderado (área bajo la curva > 0.7) a los datos de rastreo de barcos, lo que indica una fuerte asociación entre las pardelas y los barcos en los principales sitios de pesca, aunque en las regiones con alto tránsito de barcos las detecciones por radar también fueron causadas por barcos no pesqueros. Las marcas registraron la presencia del potencial de barcos pesqueros sin regular y sin reportar en aguas del oeste de África, en donde los buques mercantes son poco comunes pero la actividad pesquera es intensa. En general, los detectores por radar en las aves mostraron áreas y periodos en donde la asociación entre las aves marinas y los barcos pesqueros legales e ilegales es alta. Estos detectores por radar podrían mejorar el enfoque de los esfuerzos de conservación.

The lncRNA lnc_AABR07044470.1 promotes the mitochondrial-damaged inflammatory response to neuronal injury via miR-214-3p/PERM1 axis in acute ischemic stroke.

PURPOSE: We investigated the role of lnc_AABR07044470.1 on the occurrence and development of acute ischemic stroke (AIS) and neuronal injury by targeting the miR-214-3p/PERM1 axis to find a novel clinical drug target and prediction and treatment of AIS. METHODS: The mouse AIS animal model was used in vivo experiments and hypoxia/reoxygenation cell model in vitro was established. Firstly, infarction volume and pathological changes of mouse hippocampal neurons were detected using HE staining. Secondly, rat primary neuron apoptosis was detected by flow cytometry assay. The numbers of neuron, microglia and astrocytes were detected using immunofluorescence (IF). Furthermore, binding detection was performed by bioinformatics database and double luciferase reporter assay. Lnc_AABR07044470.1 localization was performed using fluorescence in situ hybridization (FISH).Lnc_AABR07044470.1, miR-214-3pand PERM1mRNA expression was performed using RT-qPCR. NLRP3, ASC, Caspase-1 and PERM1 protein expression was performed using Western blotting. IL-1ß was detected by ELISA assay. RESULTS: Mouse four-vessel occlusion could easily establish the animal model, and AIS animal model had an obvious time-dependence. HE staining showed that, compared with the sham group, infarction volume and pathological changes of mouse hippocampal neurons were deteriorated in the model group. Furthermore, compared with the sham group, neurons were significantly reduced, while microglia and astrocytes were significantly activated. Moreover, the bioinformatics prediction and detection of double luciferase reporter confirmed the binding site of lnc_AABR07044470.1 to miR-214-3p and miR-214-3p to Perm1. lnc_AABR07044470.1 and PERM1 expression was significantly down-regulated and miR-214-3pexpression was significantly up-regulated in AIS animal model in vivo. At the same time, the expression of inflammasome NLRP3, ASC, Caspase-1 and pro-inflammatory factor IL-1ß was significantly up-regulated in vivo and in vitro. The over-expression of lnc_AABR07044470.1 and miR-214-3p inhibitor could inhibit the neuron apoptosis and the expression of inflammasome NLRP3, ASC, Caspase-1 and pro-inflammatory factor IL-1ß and up-regulate the expression of PERM1 in vitro. Finally, over-expression of lnc_AABR07044470.1 and miR-214-3p inhibitor transfected cell model was significant in relieving the AIS and neuronal injury. CONCLUSION: Lnc_AABR07044470.1 promotes inflammatory response to neuronal injury via miR-214-3p/PERM1 axis in AIS.

Improvement of sleep and pain with lemborexant administration in patients with chronic pain: a retrospective observational study.

OBJECTIVE: Patients with chronic pain often have sleep disturbances, and many patients receive sleep medications in addition to analgesics. Although there have been scattered reports of negative pain-sleep interactions, only a few reports have investigated the efficacy of sleep medication interventions in patients with chronic pain for improving sleep disturbances and reducing pain. We retrospectively examined whether lemborexant, an orexin receptor antagonist, is effective in improving sleep disturbances and reducing pain in patients with chronic pain. This study was approved by the Ethics Committee of our hospital. METHODS: The subjects were 26 patients with chronic pain undergoing treatment at our pain clinic between July 2021 and March 2022, who had been diagnosed with insomnia, with an Athens Insomnia Scale (AIS) score of ≥6 and had been started on lemborexant. The AIS score and pain score (Numeric Rating Scale [NRS]) before and after 2 and 4 weeks of starting lemborexant were investigated. RESULTS: Patients who were already taking other sleep medications, such as benzodiazepines were switched to 5 mg of lemborexant after all the other sleep medications were discontinued. Those who had not yet used sleeping pills were started on 5 mg of lemborexant. During the study course, the dose of lemborexant was adjusted at the discretion of the attending physician, based on improvement of insomnia symptoms and secondary symptoms, such as daytime sleepiness and lightheadedness. The study finally included 21 patients, excluding 5 who could not continue taking lemborexant due to side effects, such as lightheadedness. The AIS scores significantly improved, decreasing from baseline (mean ± standard deviation: 12.5 ± 4.9) to 2 weeks (7.8 ± 3.1) and 4 weeks (5.3 ± 2.9) after the start of lemborexant. No significant difference was observed in the degree of improvement in sleep disturbance between patients with or without previous sleep medications, and there was also no statistically significant improvement in the NRS score before (6.1 ± 2.7) and after 2 weeks (5.5 ± 2.3) and 4 weeks (5.9 ± 2.2) from treatment initiation.

ASTRAL scale for predicting prognosis following intravenous thrombolysis with anterior versus posterior circulation acute ischemic stroke.

In this study, we compared whether there was any difference between the ASTRAL(Acute Stroke Registry and Analysis of Lausanne, ASTRAL) scale in predicting prognosis after IVT(Intravenous Thrombolysis, IVT) in patients with AIS(Acute Ischemic Stroke, AIS) in the ACI(Anterior Circulation Infarction, ACI) and PCI(Posterior Circulation Infarction, PCI), with the aim of providing more guiding information. Statistical analysis was performed using SPSS 25.0. When comparing the baseline characteristics, the normal distribution test was carried out first, which did not conform to the normal distribution. The continuous variables were expressed in the median and interquartile, and the nonparametric double-independent sample test was carried out. MedCalc software was used to plot ROC(Receiver Operating Characteristic, ROC) curves, calculate AUC(Area Under the Receiver Operating Characteristic Curve, AUC), and compare the prediction performance of the ASTRAL score by Delong text, and the difference of P < 0.05 was statistically significant. The AUCs of ASTRAL in predicting poor prognosis of ACI and PCI patients after IVT were 0.768 and 0.773, respectively. There was no difference in the AUC of ASTRAL score between ACI and PCI(P > 0.05). The ASTRAL scale has consistent prognostic predictive value for AIS in the anterior and posterior circulatory systems and is a reliable tool for predicting poor prognosis of patients with ACI and PCI after IVT.

Prognostic outcome of intravenous thrombolysis in elderly patients aged ≥ 60 years with acute ischemic stroke by ASTRAL and THRIVE scales.

This study aimed to validate the predictive performance of ASTRAL and THRIVE scales when used for patients aged 60 years and older with acute ischemic stroke (AIS) after intravenous thrombolysis (IVT). All enrolled patients received IVT therapy. The enrolled patients were divided into two groups in accordance with the modified Rankin scale(mRS) score at the time of discharge: good-outcome (mRS ≤ 2) and poor-outcome (mRS ≥ 3) groups. The receiver operating characteristic (ROC) curve was plotted using MedCalc software, the area under the ROC curve (AUC) was calculated. The Delong test was used to compare the predictive performance of ASTRAL and THRIVE scales, with P < 0.05 being considered a statistically significant difference. The AUCs of ASTRAL and THRIVE in predicting poor outcomes after thrombolysis in elderly patients with AIS were 0.771 and 0.701, respectively. The difference in AUC between ASTRAL and THRIVE was 0.070, and a statistically significant difference (P < 0.05) was found. ASTRAL's predictive performance was better than that of THRIVE. ASTRAL is a reliable predictive tool for assessing the poor outcome of IVT therapy for elderly patients aged ≥ 60 years with AIS.

High expression of eukaryotic elongation factor 1-alpha-2 in lung adenocarcinoma is associated with poor prognosis.

Eukaryotic elongation factor 1 alpha 2 (eEF1A2) encodes an isoform of the alpha subunit of the elongation factor 1 complex and is responsible for the enzymatic delivery of aminoacyl tRNA to the ribosome. Our proteomic analysis has identified eEF1A2 as one of the proteins expressed during malignant progression from adenocarcinoma in situ (AIS) to early invasive lung adenocarcinoma. The expression level of eEF1A2 in 175 lung adenocarcinomas was examined by immunohistochemical staining in relation to patient prognosis and clinicopathological factors. Quantitative PCR analysis and fluorescence in situ hybridization (FISH) were performed to evaluate the amplification of the eEF1A2 gene. Relatively high expression of eEF1A2 was observed in invasive adenocarcinoma (39/144 cases) relative to minimally invasive adenocarcinoma (1/10 cases) or AIS (0/21 cases). Among invasive adenocarcinomas, solid-type adenocarcinoma (15/32 cases, 47%) showed higher expression than other histological subtypes (23/92, 25%). Patients with eEF1A2-positive tumors had a significantly poorer prognosis than those with eEF1A2-negative tumors. Of the five tumors that were eEF1A2-positive, two cases showed amplified genomic eEF1A2 DNA, which was confirmed by both qPCR and FISH. These findings indicate that eEF1A2 overexpression occurs in the course of malignant transformation of lung adenocarcinomas and is partly due to eEF1A2 gene amplification.

Circulating soluble CD163 is associated with reduced Glasgow Coma Scale Score and 1-year all-cause mortality in traumatized patients.

Soluble CD163 (sCD163) is a biomarker of macrophage activation, not previously investigated in the circulation of traumatized patients. A biobank of 398 adult trauma patients was analyzed. Patients with an Injury Severity Score (ISS) >8 served as trauma patients (n = 195) and those with ISS ≤8 as trauma controls (n = 203). Serum samples obtained upon admission, 15h and 72h after were analyzed for sCD163 using an in-house ELISA. Multiple linear regression was used to analyze the association between admission levels of sCD163 with, 1: overall trauma severity (ISS), and 2: severity of injury to specified organs using Abbreviated Injury Score (AIS) and Glasgow Coma Scale (GCS). The association between the peak level of sCD163 with 1-year all-cause mortality was analyzed by logistic regression analysis. Median admission levels of sCD163 were higher in trauma patients than trauma controls [2.32 (IQR 1.73 to 2.86) vs. 1.92 (IQR 1.41 to 2.51) mg/L, p < 0.01]. Worsening GCS score was associated with a 10.3% (95% CI: 17.0 to 3.1, p < 0.01) increase in sCD163. Increasing Head-AIS score was associated with a 5.1% (95% CI: -0.5 to 11.0, p = 0.07) increase in sCD163. The remaining AIS scores and ISS were not consistently associated with sCD163 admission levels. Each mg/L increase in sCD163 peak level had an odds ratio 1.34 (95%CI: 0.98 to 1.83), p = 0.06) after adjustment for age, sex, and GCS. Circulating sCD163 is increased in traumatized patients and associated with worsening GCS. Our findings suggest an association between circulating sCD163 levels with 1-year all-cause mortality.

Effect of teleneurology on door-to-needle times for tenecteplase in acute ischemic stroke.

INTRODUCTION: Intravenous thrombolysis remains the primary treatment for acute ischemic stroke (AIS); however, administration is time sensitive. Teleneurology services have increased in popularity in recent years due to their ability to aid in triaging patients with neurological conditions. Teleneurology services were implemented at this comprehensive stroke center, in August 2023 to aid in streamlining the administration of tenecteplase in AIS patients. Currently, there are no studies assessing whether the implementation of teleneurology services at a comprehensive stroke center influences tenecteplase door-to-needle time. The purpose of this study is to evaluate the difference in door-to-needle times when tenecteplase is administered with versus without a teleneurology consult. METHODS: This was an institutional review board approved, retrospective cohort study conducted at a single comprehensive stroke center. Adult patients who presented to the emergency department between January 1st, 2022 and April 1st, 2023 were included if they received tenecteplase for the treatment of AIS. The primary outcome was door-to-needle time, defined as the moment the patient first enters the door of the emergency department to the moment the IV bolus of fibrinolytic is administered. Secondary outcomes included the proportion of patients with door-to-needle time within 45 min, neurological improvement at 24 h and discharge, and rate of hemorrhagic conversion. RESULTS: A total of 93 patients were included with 43 patients in the pre-teleneurology group and 50 patients in the post-teleneurology group. Baseline characteristics were comparable between both treatment groups. The median door-to-needle time was significantly reduced in the post-teleneurology group (49 minutes [IQR, 40.0-70.0] preintervention vs. 34.5 minutes [IQR, 23.8-43.0] postintervention, p < 0.01). For secondary outcomes, the post-teleneurology group had more patients with a door-to-needle time within 45 minutes (44.2% vs. 80.0%, p < 0.01). There was no significant difference in early neurological improvement (58.1% vs. 54.0%), neurological improvement at discharge (60.5% vs. 62.0%), or hemorrhagic conversion (7.0% vs. 12.0%). CONCLUSION: Among patients who received tenecteplase for the treatment of AIS, there was a significant reduction in door-to-needle time with the use of teleneurology services. There was no difference in neurological improvement or rate of hemorrhagic conversion.

Radiological Outcomes of Re-tethering for Adolescent Idiopathic Scoliosis: A 2-to-5-year Follow-Up Case Series After Index Vertebral Body Tethering Failure.

PURPOSE: Vertebral Body Tethering (VBT) has been shown to have a less predictable outcome compared to spinal fusion in patients with adolescent idiopathic scoliosis (AIS). Tether breakage is a common mechanical event that sometimes leads to loss of correction. No data has been published that evaluates the outcome of re-tethering in patients who underwent revision surgery for failed VBT, which was the purpose of this study. METHODS: This is an analysis of a prospectively collected single center database of 290 patients who have had VBT. Patients for this study were included if they have had re-tethering after failed VBT and a minimum follow up of 24 months after index surgery as well as a minimum follow up of 12 months after revision surgery. Revision surgeries included tether exchange, tether reinforcement and/or mono- and bisegmental lateral fusion. Main outcome of interest was curve magnitude at latest follow up. RESULTS: 11 patients were identified who received VBT for 16 curves of which 13 curves have had failed index surgery. Mean follow up from index surgery was 40 months, time between index and revision surgery was 22 months and latest follow up after revision surgery 19 months. Re-tethering resulted in an additional correction of 42% for thoracic and 63% for thoracolumbar curves. These results remained clinically stable with only minor loss of correction at final follow up. No patient underwent or was indicated for spinal fusion. CONCLUSION: Re-tethering is feasible and able to achieve additional correction and a sustainable result.

The efficacy of anterior vertebral body tethering in lenke type 6 curves for adolescent idiopathic scoliosis.

PURPOSE: Spinal fusion is the standard treatment for severe forms of adolescent idiopathic scoliosis (AIS). However, with the lowest instrumented vertebra that is usually located at L3 or L4, patients are prone to develop adjacent segment degeneration in the long term. Vertebral body tethering (VBT) as motion preserving technique has become an alternative for select patients with AIS. Several studies have presented the outcome after thoracic VBT but no study has analyzed the outcome after VBT for Lenke type 6 curves. METHODS: This is a retrospective single center data analysis of patients who have had bilateral VBT for Lenke type 6 curves and a minimum follow up of 24 months. Radiographic analysis was performed on several time points. Suspected tether breakages were additionally analyzed with respect to location and time at occurrence. RESULTS: 25 patients were included. Immediate thoracic curve correction was 55.4% and 71.7% for TL/L curves. Loss of correction was higher for TL/L curves and resulted in a correction rate of 48.3% for thoracic curves and 48.9% for TL/L curves at 24 months post-operatively. 22 patients were suspected to have at least one segment with a tether breakage. Three patients required a re-VBT but no patient received posterior spinal fusion. CONCLUSION: Bilateral VBT for Lenke type 6 curves is feasible and shows a significant curve correction for thoracic and TL/L curves at a minimum of 24 months post-operatively. Tether breakage rate and loss of correction remain an unfavorable observation that needs to be improved in the future.

Early-term outcome of apical fusion with vertebral body tethering for thoracolumbar curves in adolescent idiopathic scoliosis: a preliminary study.

INTRODUCTION: Vertebral body tethering (VBT) has become an alternative option for select patients with idiopathic scoliosis. However, studies have shown a high number of tether breakages, specifically after thoracolumbar (TL) VBT, that can have a negative impact on the outcome, when the breakage occurs within the first year after surgery. In order to overcome this problem, we have started to apply an apical fusion (AF) in combination with TL VBT for select patients. This study aims to analyze the outcome after AF plus VBT. METHODS: This is a retrospective single surgeon's data analysis. All patients were included who have had TL VBT after January 2022 and a follow-up of 12 months. Patients were grouped based on whether they only had VBT or VBT + AF. RESULTS: Twenty-five patients were analyzed (15 VBT, 10 VBT + AF). Both groups showed a significant curve correction for thoracic and TL curves. Minor loss of correction was observed in both groups. A significant difference was seen regarding early tether breakages, which were found in 60% of VBT patients and 10% of VBT + AF patients. CONCLUSION: The preliminary data shows a significant reduction of early tether breakages when TL VBT is applied in combination with AF.

Assessing progressive changes in axial plane vertebral deformity in adolescent idiopathic scoliosis using sequential magnetic resonance imaging.

PURPOSE: To understand how the axial plane deformity contributes to progression of the three-dimensional spinal deformity of Adolescent Idiopathic Scoliosis (AIS), with a main thoracic curve type, using a series of sequential magnetic resonance images (MRI). METHODS: Twenty-seven AIS patients (at scan 1: mean 12.4 years (± 1.5), mean Cobb angle 29.1°(± 8.8°)) had 3 MRI scans (T4-L1) performed at intervals of mean 0.7 years (± 0.4). The outer profile of the superior and inferior endplates were traced on a reformatted axial image using ImageJ (NIH). Endplate AVR, and intravertebral rotation (IVR), defined as the difference between superior and inferior endplate AVR, was calculated for each vertebral level. RESULTS: For all patients and scans, the mean AVR was greatest at the curve apex, with AVR diminishing in a caudal and cephalic direction from the apex. At scan 3 the mean apical AVR was 15.1°(± 4.6°) with a mean change in apical AVR between MRI 1 and 3 of 2.7°(± 2.9°). The increase in standing height between MRI 1 and 3 was mean 7.4 cm (± 4.6). Linear regression showed a positive correlation between apical AVR and Cobb angle (R2 = 0.57, P < 0.001), and a positive correlation between apical AVR and rib hump (R2 = 0.54, p < 0.001). The mean change in IVR was greater 3 vertebral levels cephalic and caudal to the apex (1.4°(± 4.1°) and 1.2°(± 2.0°), respectively), compared to the apex (0.4°(± 3.1°)). CONCLUSIONS: AVR increased, during curve progression, most markedly at the curve apex. The greatest IVR was observed at the periapical levels, with the apex by contrast having only a modest degree of rotation, suggesting the periapical vertebral levels of the scoliosis deformity may be a significant driver in the progression of AIS.

Tissue response following implantation with the posterior dynamic distraction device (PDDD) in adolescent idiopathic scoliosis (AIS).

PURPOSE: The PDDD is a ratchet-based, unidirectional expandable rod to treat adolescent idiopathic scoliosis (AIS), primarily by correcting scoliotic deformity without full spinal fusion. We hypothesized that the device will be fully tolerated by the host and, if aseptic screw loosening occurs, it will be unrelated to wear particle formation. METHODS: This study comprised tissue samples from seven patients from a prospective study (NCT04296903) to assess the PDDD's safety and benefits, reoperated due to complications. Host response was assessed from histological slides (four levels/implant) in accordance with GLP and ISO10993-6:2016. The elementary chemical composition of wear particles present in tissue sections was quantified by energy dispersive X-ray spectroscopy (EDX). RESULTS: Host reaction was minor, characterized by low levels of diverse inflammatory cells, mild fibrosis, occasional small necrotic foci, neovascularization, hemorrhage, and, rarely, small bone fragments. Twenty-four of 28 tissue sections displayed varying degrees of wear particles (black discoloration), and most sections (17) were scored as 1 (< 25% of the sample). The discoloration observed corresponded to black-appearing, fine granular pigment. EDX analysis confirmed particles were composed of titanium, aluminum, and vanadium. Twenty-six of 28 samples were scored zero for necrosis and 2/28 were scored 1. Eleven samples were scored zero for fibrosis, 12 as 1, and five as 2. No aseptic screw loosening occurred. CONCLUSION: The PDDD induced minimal host reaction with little or no degeneration, inflammation or fibrosis. No changes present could be expected to promote device failure. The PDDD implant for treating AIS is well-tolerated and locally safe.

Does the coronal deformity angular ratio affect bracing outcome in adolescent idiopathic scoliosis?

PURPOSE: To examine if coronal deformity angular ratio (C-DAR) serves as a predictor for progression to surgical magnitude in patients with Adolescent Idiopathic Scoliosis (AIS) treated with thoracolumbar sacral orthosis (TLSO). METHODS: Patients with AIS, prescribed a full-time TLSO, Cobb angle 20-40°, Risser 0-2, who wore the brace ≥ 12.9 h and reached skeletal maturity/surgery were included retrospectively. C-DAR was defined as the Cobb angle divided by the number of vertebrae in the curve, yielding a larger value in short curves. The association between C-DAR and the risk of progression to surgical magnitude (> 45°) was assessed. Secondly, we evaluated the association between pre-treatment Cobb angle and in-brace correction on the risk of progression to > 45°. RESULTS: We included 165 patients with a mean Cobb angle of 30 ± 6°. Of these, 46/165 (28%) progressed ≥ 6° and 26/165 (16%) reached surgical magnitude at the end of treatment. C-DAR was a significant predictor for risk of progression to surgical magnitude with an OR of 1.9 (CI 1.2-2.9) per unit increase in C-DAR. A threshold value of 5.15 was established and demonstrated an OR 5.9 (CI 2.1-17.9) for curve progression to a surgical magnitude. Likewise, pre-treatment Cobb angle showed a significant OR 1.3(CI 1.2-1.4) per degree increase in Cobb, whereas in-brace % correction showed OR 0.96 (CI 0.93-0.98). CONCLUSION: C-DAR is an independent predictor for progression to a surgical magnitude in AIS patients treated with bracing. Patients with a higher C-DAR should be counseled to help set realistic expectations regarding the likelihood of curve progression despite compliance with brace wear.