bluuebunny/crossref_metadata_2025 huggingface dataset:
Risk prediction models for diabetic foot ulcer development or amputation: a review of reviews
Authors: Kaka Anjum S. , Landsteiner Adrienne , Ensrud Kristine E. , Logan Brittany , Sowerby Catherine , Ullman Kristen , Yoon Patrick , Wilt Timothy J. , Sultan Shahnaz
Published: March 2023

Background

In adults with diabetes, diabetic foot ulcer (DFU) and amputation are common and associated with significant morbidity and mortality.

Purpose

Identify tools predicting risk of DFU or amputation that are prognostically accurate and clinically feasible.

Methods

We searched for systematic reviews (SRs) of tools predicting DFU or amputation published in multiple databases from initiation to January, 2023. We assessed risk of bias (ROB) and provided a narrative review of reviews describing performance characteristics (calibration and discrimination) of prognostically accurate tools. For such tools, we additionally reviewed original studies to ascertain clinical applicability and usability (variables included, score calculation, and risk categorization).

Results

We identified 3 eligible SRs predicting DFU or amputation risk. Two recent SRs (2020 and 2021) were rated as moderate and low ROB respectively. Four risk prediction models – Boyko, Martins‐Mendes (simplified), Martins‐Mendes (original), and PODUS 2020 had good prognostic accuracy for predicting DFU or amputation over time horizons ranging from 1‐ to 5‐years. PODUS 2020 predicts absolute average risk (e.g., 6% risk of DFU at 2 years) and consists of 3‐binary variables with a simple, summative scoring (0–4) making it feasible for clinic use. The other 3 models categorize risk subjectively (e.g., high‐risk for DFU at 3 years), include 2–7 variables, and require a calculation device. No data exist to inform rescreening intervals. Furthermore, the effectiveness of targeted interventions in decreasing incidence of DFU or amputation in response to prediction scores is unknown.

Conclusions

In this review of reviews, we identified 4 prognostically accurate models that predict DFU or amputation in persons with diabetes. The PODUS 2020 model, predicting absolute average DFU risk at 2 years, has the most favorable prognostic accuracy and is clinically feasible. Rescreening intervals and effectiveness of intervention based on prediction score are uncertain.
Detection of tick-borne encephalitis virus in ear tissue and dried blood spots from naturally infected wild rodents
Authors: Pascoe Emily L. , de Vries Ankje , Esser Helen J. , Koenraadt Constantianus J. M. , Sprong Hein
Published: March 2023

Background

Tick-borne encephalitis virus (TBEV) can cause severe neurological disease in humans. Its geographical distribution is expanding in Western Europe with unresolved causes and spatial patterns, necessitating enhanced surveillance. Monitoring the virus in the environment is complicated, as it usually relies on destructive sampling of small rodents to test organs for TBEV, which in addition to ethical considerations also raises issues for long-term monitoring or longitudinal studies. Moreover, even when the virus is not detected in the blood or organs of the rodent, TBEV can still be transmitted from an infected tick to uninfected ticks feeding nearby. This is due to the ability of TBEV to replicate and migrate locally within the epidermis of small mammals, including those that do not appear to have systemic infection. This suggests that the virus may be detectable in skin biopsies, which has been confirmed in experimentally infected laboratory rodents, but it remains unknown if this sample type may be a viable alternative to destructively obtained samples in the monitoring of natural TBEV infection. Here we test ear tissue and dried blood spot (DBS) samples from rodents to determine whether TBEV-RNA can be detected in biological samples obtained non-destructively.

Methods

Rodents were live-trapped and sampled at three woodland areas in The Netherlands where presence of TBEV has previously been recorded. Ear tissue (n = 79) and DBSs (n = 112) were collected from a total of 117 individuals and were tested for TBEV-RNA by real-time RT-PCR.

Results

TBEV-RNA was detected in five rodents (4.3% of tested individuals), all of which had a TBEV-positive ear sample, while only two out of four of these individuals (for which a DBS was available) had a positive DBS. This equated to 6.3% of ear samples and 1.8% of DBSs testing positive for TBEV-RNA.

Conclusions

We provide the first evidence to our knowledge that TBEV-RNA can be detected in samples obtained non-destructively from naturally infected wild rodents, providing a viable sampling alternative suitable for longitudinal surveillance of the virus.

Graphical Abstract
Oral cavity-derived stem cells and preclinical models of jaw-bone defects for bone tissue engineering
Authors: Zhao Jie , Zhou Ying-Hui , Zhao Ya-Qing , Gao Zheng-Rong , Ouyang Ze-Yue , Ye Qin , Liu Qiong , Chen Yun , Tan Li , Zhang Shao-Hui , Feng Yao , Hu Jing , Dusenge Marie Aimee , Feng Yun-Zhi , Guo Yue
Published: March 2023

Background

Jaw-bone defects caused by various diseases lead to aesthetic and functional complications, which can seriously affect the life quality of patients. Current treatments cannot fully meet the needs of reconstruction of jaw-bone defects. Thus, the research and application of bone tissue engineering are a “hot topic.” As seed cells for engineering of jaw-bone tissue, oral cavity-derived stem cells have been explored and used widely. Models of jaw-bone defect are excellent tools for the study of bone defect repair in vivo. Different types of bone defect repair require different stem cells and bone defect models. This review aimed to better understand the research status of oral and maxillofacial bone regeneration.

Main text

Data were gathered from PubMed searches and references from relevant studies using the search phrases “bone” AND (“PDLSC” OR “DPSC” OR “SCAP” OR “GMSC” OR “SHED” OR “DFSC” OR “ABMSC” OR “TGPC”); (“jaw” OR “alveolar”) AND “bone defect.” We screened studies that focus on “bone formation of oral cavity-derived stem cells” and “jaw bone defect models,” and reviewed the advantages and disadvantages of oral cavity-derived stem cells and preclinical model of jaw-bone defect models.

Conclusion

The type of cell and animal model should be selected according to the specific research purpose and disease type. This review can provide a foundation for the selection of oral cavity-derived stem cells and defect models in tissue engineering of the jaw bone.
Highly-purified rapidly expanding clones, RECs, are superior for functional-mitochondrial transfer
Authors: Yang Jiahao , Liu Lu , Oda Yasuaki , Wada Keisuke , Ago Mako , Matsuda Shinichiro , Hattori Miho , Goto Tsukimi , Kawashima Yuki , Matsuzaki Yumi , Taketani Takeshi
Published: March 2023

Background

Mitochondrial dysfunction caused by mutations in mitochondrial DNA (mtDNA) or nuclear DNA, which codes for mitochondrial components, are known to be associated with various genetic and congenital disorders. These mitochondrial disorders not only impair energy production but also affect mitochondrial functions and have no effective treatment. Mesenchymal stem cells (MSCs) are known to migrate to damaged sites and carry out mitochondrial transfer. MSCs grown using conventional culture methods exhibit heterogeneous cellular characteristics. In contrast, highly purified MSCs, namely the rapidly expanding clones (RECs) isolated by single-cell sorting, display uniform MSCs functionality. Therefore, we examined the differences between RECs and MSCs to assess the efficacy of mitochondrial transfer.

Methods

We established mitochondria-deficient cell lines (ρ0 A549 and ρ0 HeLa cell lines) using ethidium bromide. Mitochondrial transfer from RECs/MSCs to ρ0 cells was confirmed by PCR and flow cytometry analysis. We examined several mitochondrial functions including ATP, reactive oxygen species, mitochondrial membrane potential, and oxygen consumption rate (OCR). The route of mitochondrial transfer was identified using inhibition assays for microtubules/tunneling nanotubes, gap junctions, or microvesicles using transwell assay and molecular inhibitors.

Results

Co-culture of ρ0 cells with MSCs or RECs led to restoration of the mtDNA content. RECs transferred more mitochondria to ρ0 cells compared to that by MSCs. The recovery of mitochondrial function, including ATP, OCR, mitochondrial membrane potential, and mitochondrial swelling in ρ0 cells co-cultured with RECs was superior than that in cells co-cultured with MSCs. Inhibition assays for each pathway revealed that RECs were sensitive to endocytosis inhibitor, dynasore.

Conclusions

RECs might serve as a potential therapeutic strategy for diseases linked to mitochondrial dysfunction by donating healthy mitochondria.
Cranial and mandibular anatomy of Plastomenus thomasii and a new time-tree of trionychid evolution
Authors: Evers Serjoscha W. , Chapelle Kimberley E. J. , Joyce Walter G.
Published: March 2023

Trionychid (softshell) turtles have a peculiar bauplan, which includes shell reductions and cranial elongation. Despite a rich fossil record dating back to the Early Cretaceous, the evolutionary origin of the trionychid bauplan is poorly understood, as even old fossils show great anatomical similarities to extant species. Documenting structural detail of fossil trionychids may help resolve the evolutionary history of the group. Here, we study the cranial and mandibular anatomy of Plastomenus thomasii using µCT scanning. Plastomenus thomasii belongs to the Plastomenidae, a long-lived (Santonian–Eocene) clade with uncertain affinities among trionychid subclades. The skulls of known plastomenids are characterized by unusual features otherwise not known among trionychids, such as extremely elongated, spatulate mandibular symphyses. We use anatomical observations for updated phylogenetic analyses using both parsimony and Bayesian methods. There is strong support across methods for stem-cyclanorbine affinities for plastomenids. The inclusion of stratigraphic data in our Bayesian analysis indicates that a range of Cretaceous Asian fossils including Perochelys lamadongensis may be stem-trionychids, suggesting that many features of trionychid anatomy evolved prior to the appearance of the crown group. Divergence time estimates from Bayesian tip-dating for the origin of crown Trionychia (134.0 Ma) and Pan-Trionychidae (123.8 Ma) constrain the evolutionary time span during which the trionychid bauplan has evolved to a range of < 11 million years. Bayesian rate estimation implies high morphological rates during early softshell turtle evolution. If correct, plastomenids partially fill the stratigraphic gap which results from shallow divergence times of crown cyclanorbines during the late Eocene.
Exogenous Glutathione enhances tolerance of the potato (Solanum tuberosum L.) to cadmium stress by regulating the biosynthesis of phenylpropanoid and the signal transduction of plant hormones
Authors: Kang Yichen , Yao Yanhong , Liu Yuhui , Shi Mingfu , Zhang Weina , Zhang Ruyan , Li Hong , Qin Shuhao , Yang Xinyu
Published: March 2023

Background

Cadmium (Cd) pollution has brought harm to the growth and development of potato. Glutathione (GSH) is an important antioxidant that may play an active role in the response of a potato to Cd stress. However, how GSH influences the effect of Cd on potatoes is unknown. In this study, we investigated the effects of exogenous GSH on the phenylpropanoid biosynthesis pathway and plant hormone signal transduction pathway in potatoes under Cd stress to explore new ideas for how potatoes respond to Cd stress. We cultured 21-day-old 'Atlantic’ plantlets in Murashige and Skoog (MS) medium supplemented with 500 μmol/L CdCl2or 500 μmol/L CdCl2 + 400 μmol/L GSH. We then investigated the activities of key enzymes in the phenylpropanoid biosynthesis pathway, hormone levels, and the expression levels of related genes at different time points.

Results

Analysis showed that 96 h of treatment with glutathione led to an increase in the expression levels of genes encoding phenylalanine ammonia-lyase (PAL), cinnamyl alcohol dehydrogenase (CAD) and peroxidase (POD); an increase in the enzymic activities of PAL, CAD and POD; and an increase in the content of lignin. The content of lignin was positively correlated with the expression levels of several genes (PAL: PG0031457, CAD: PG0005359, POD: PG0011640 and PG0015106). In addition, the levels of Salicylic acid (SA) and Jasmonic acid (JA) increased significantly, the expression levels of the genes encoding transcription factor TGA (PG2023696), pathogenesis-related protein 1 (PR1) (PG0005111), and the transcription inhibitor Aux/IAA (PG0006093) all increased while the expression levels of jasmonate ZIM domain-containing protein (JAZ) (PG0004367), auxin influx carrier (AUX) (PG0006550) and auxin response factor (ARF) (PG0005794) all decreased. We also observed a reduction in the content of IAA.

Conclusion

Exogenous GSH improved the tolerance of potato, Atlantic cv. to Cd stress by regulating the phenylpropanoid biosynthesis pathway and the plant hormone signal transduction pathway.

Graphical Abstract
Novel Genetic Subtypes of Urothelial Carcinoma With Differential Outcomes on Immune Checkpoint Blockade
Authors: Sarfaty Michal , Golkaram Mahdi , Funt Samuel A. , Al-Ahmadie Hikmat , Kaplan Shannon , Song Fan , Regazzi Ashley , Makarov Vladimir , Kuo Fengshen , Ostrovnaya Irina , Seshan Venkatraman , Zhao Chen , Greenbaum Benjamin , Liu Li , Rosenberg Jonathan E. , Chan Timothy A.
Published: March 2023

PURPOSE

Immune checkpoint blockade (ICB) therapy has significantly improved clinical outcomes in bladder cancer. Identification of correlates of benefit is critical to select appropriate therapy for individual patients.

METHODS

To reveal genetic variables associated with benefit from ICB, we performed whole-exome sequencing on tumor specimens from 88 patients with advanced bladder cancer treated with ICB.

RESULTS

We identified several genetic factors that correlated with progression-free and overall survival after ICB therapy including ARID1A mutation, tumor mutational burden, intratumoral heterogeneity, the ratio of nonsynonymous to synonymous mutations in the immunopeptidome (immune dN/dS), and tumor cell purity. In addition, we noted that neutrophil-to-lymphocyte ratio and smoking history were negatively associated with overall survival. These genetic characteristics define four molecular subtypes demonstrating differential sensitivity to ICB. We validated the association of these four subtypes with clinical benefit from ICB in an independent cohort (IMvigor210). Finally, we showed that these molecular subtypes also correlate with outcome, although with distinct relationships, among patients not treated with ICB using The Cancer Genome Atlas (TCGA) bladder cancer cohort. Using parallel RNA sequencing data, the subtypes were also shown to correlate with immune infiltration and inflammation, respectively, in the IMvigor210 and TCGA cohorts.

CONCLUSION

Together, our study defines molecular subgroups of bladder cancer that influence benefit from ICB.
Trans* (Dis)appearance at the Mexican Frontier
Authors: Sánchez Cruz Jorge
Published: March 2023

This article positions Teresa Margolles's Ya basta hijos de puta (2018) as a refusal of trans* disappearance created by capitalistic initiatives of renovation, by the failures of the Mexican state, and by transphobic violence. Through the triangulation of three objects, a stone, a legal document, and a sound recording, intertwined with seventeen photographs of trans* people in Ciudad Juárez, Mexico, the article also proposes that Margolles's recent aesthetic shift engages transness to open up a coalitional travesti-trans* studies between the North and South. A hemispheric conversation in which praxis and theory meet and where Ya basta hijos de puta as praxis demands on feeling destruction through the “touching” of the stone, on seeing the legal foreclosures through a death certificate, and on hearing of disappearance through the recording, the sound of the afterlife of transness.
Falling into Pam's World
Authors: McGuffie Allison
Published: March 2023

Narrative cinema holds the unique potential to absorb audiences in the sensory world of its characters. When mobilized in the service of depicting trans* experience, the specificity of the medium can generate deep empathy for trans* lives, an important ethical objective, especially in a society in which trans* lives are under attack. Through close formal analysis, this article shows how the 1997 film Ma vie en rose accomplishes this project by cinematically aligning film spectators with a transgender child's audiovisual perception. Ma vie en rose immerses the film spectator in Ludovic's fantasy world where they are completely accepted as they are, inspiring the spectator to become personally invested in Ludovic's well-being, and potentially contributing to a real-world social environment that fosters livable lives for gender-nonconforming children.
A Right to Transition?
Authors: Perkins Kathryn J. , Harting Grant , Ortiz Soto Evelyn
Published: March 2023

How does the law determine gender and transgender for the purposes of admission to gender-segregated spaces? This article examines this question to understand how transgender identity is legally constructed in gender-segregated spaces. Using trans feminist legal theory, this article explores how the state conceptualizes and re/incorporates transness in a binary gender order. Through case studies of access to gender transition in gender-segregated educational and carceral spaces, the authors find that judges engage in gender naturalization work to legally construct transgender identity in ways that reinforce sexist conceptualizations of immutable and binary gender. We conclude with a discussion of the implications of this narrow construction of transgender identity for a trans feminist jurisprudence and politics.
118 A Cost Effectiveness Analysis of Two Treatment Strategies for Trigeminal Neuralgia in Ontario
Authors: Duda Taylor , Lannon Melissa , Martyniuk Amanda , Farrokyar Forough , Sharma Sunjay Vishnu
Published: March 2023

INTRODUCTION:

Trigeminal neuralgia is a debilitating disease affecting 4-27/100000 people annually. In Ontario, over 2000 patients will be cared for through a universal government payer model. Interventions for profound pain include medical and surgical therapies, among other options. The global expected cost of these approaches is unknown.

METHODS:

Costs were gathered from the Canadian Institute for Health Information, Ontario Drug Benefit Formulary, and Ontario Ministry of Health Schedule of Benefits for Physician Services Under the Health Acct. Academic literature was used to estimate unavailable items. A cost-benefit Markov model was created for each strategy with literature-based event rates for annual cycles from year one to five, followed by a linear recurrent cycle from year six to ten. Incremental cost-effectiveness ratios (ICERs) were calculated based on incremental cost in $CAD in 2022 per patient with a pain free year.

RESULTS:

Base case cost per patient was $10866 at ten years in the “MVD first” group and $10710 in the “carbamazepine first” group. The break-even point is slightly longer than ten years. Surgical cost is significantly higher at year one, at $9733 versus $1903. Ten year ICER was $1014 for “MVD first,” with strict superiority beyond this time point. One way deterministic sensitivity analysis for multiple factors suggested the highest cost variability and ICER variability was due to surgery cost, medication failure rate, and medication cost.

CONCLUSIONS:

Economic beneift is established to a “MVD first” strategy in the Ontario context with strict superiority beyond the ten-year horizon. If an arbitrary ICER of $50000 is used, benefit is established at four years. MVD could be considered broadly as a cost-effective and cost-saving measure in patients expected to live beyond these horizons.
146 Functional Priorities in High Cervical Spinal Cord Injury: Implications for Upper Limb Nerve Transfer Surgery
Authors: Javeed Saad , Greenberg Jacob K. , Zhang Justin , Dibble Christopher , Khalifeh Jawad M. , Wilson Thomas J. , Zager Eric L. , Faraji Amir H. , Mahan Mark Alexander , Midha Rajiv , Burks Shelby , Levi Allan D. , Belzberg Allan J. , Jun-San Yang Lynda , Juknis Naringa , Ray Zack
Published: March 2023

INTRODUCTION:

High cervical spinal cord injury (SCI) results in complete impairment in upper limb function. Nerve transfer is an innovative reinnervation strategy for upper limb reanimation following SCI. However, the impact of upper limb motor recovery on the degree of long-term functional outcomes remains unknown.

METHODS:

A prospective cohort of high cervical SCI (C1-C4) patients enrolled in SCI model systems (SCIMS) was included. Baseline neurological examinations and functional independence measures (FIM) in eating, bladder-function, and transfers (bed/wheelchair/chair) were evaluated. At one-year follow-up, functional independence was compared in patients who gained recovery (motor grade >=3) in C5-elbow flexion, C6-wrist extension, C7-elbow extension, and C8-finger flexion. A multivariable logistic regression evaluated the impact of motor recovery on functional independence on composite outcome of feeding, bladder-function, and transfers.

RESULTS:

Between 1992-2016, 405 high cervical SCI patients were included. At baseline, 97% patients had impaired upper limb function with inability in all functions. At one-year follow-up, the largest proportion of patients gaining independence in eating, bladder-function, and transfers had recovery in C8-finger-flexion and C6-wrist-extension. C5-elbow-flexion recovery had lowest translation into functional independence. Patients who achieved C7-elbow-extension were able to transfer independently. On multivariable analysis, C8-finger-flexion recovery had 12-times higher odds (p=0.004) and C6-wrist-extension recovery had 7-times higher odds (p=0.04) of gaining functional independence in composite outcome. Age >=60 years and motor complete SCI (ASIA-A-B) were associated with reduced odds of gaining independence. 8% patients improved ASIA grades from baseline to 1-year.

CONCLUSIONS:

Following cervical SCI, C8-finger-flexion and C6-wrist-extension recovery can maximize functional independence. Recovery of C7-elbow-extension can increase transfer capability. This information may prioritize reinnervation strategies for individualized decision-making for nerve transfers in high cervical SCI.
158 Controlling Glioblastoma Invasion In Vivo With CD97
Authors: Eichberg Daniel Green , Slepak Tatiana , Guyot Manuela , Walters Winston , Komotar Ricardo Jorge , Ivan Michael E.
Published: March 2023

INTRODUCTION:

Increased levels of adhesion G Protein-Coupled Receptor (GPCR) CD97 have been detected in multiple metastatic cancers. Glioblastoma (GBM), a Grade-IV Glioma, also overexpress this receptor, and its levels positively correlate with more aggressive GBM invasion.

METHODS:

CD97 consists of two distinct domains: the large extracellular fragment interacting with ECM and other cell surface receptors and the GPCR core that activates heterotrimeric G Proteins G12/13. To investigate the mechanism of action of CD97, we generated a CD97 knockdown (shCD97) and overexpression (CD97-WT) constructs. Additionally, we generated two functional mutants: a constitutively active mutant lacking the N-Terminus (dNTF) and dominant-negative mutant (H436A) that cannot activate G-Proteins downstream. Glioma Stem Cells (GSC) were transduced by control and CD97 lentiviral constructs and implanted into mouse brains. Once tumors formed the brains were harvested, sliced, and immunostained to evaluate invasion and proliferation. Comparing mutants to control, dunnett’s multiple comparisons test was used for statistical analysis.

RESULTS:

Similar to CD97-WT, we found that both dNTF and H436A, increase tumor volume (p < 0.05). In contrast, the shCD97 mutant decreased tumor size (p < 0.05). Interestingly, only dNTF significantly increased tumor cell proliferation (p < 0.005), yet CD97-WT and H436A affected proliferation of non-tumor cells in the tumor bulk, indicating that this process requires the N-Terminus Fragment. In addition, over-expression of CD97-WT dramatically increases tumor invasion along myelinated fibers of corpus collosum, and tumor spread in the brain tissue (p < 0.05). Yet, the H436A mutant produced large, compact, and non-invasive tumors with sharp borders (p < 0.05) indicating that cell migration requires activation of G12/13. Surprisingly, immunostaining revealed that CD97 knockdown cells displayed invasive phenotype.

CONCLUSIONS:

Our results demonstrate the dual role CD97 plays in GBM invasion and proliferation, alluding to the molecular mechanisms that can potentially be targeted in GBM treatment.
162 Evaluating Risk of Recurrence in Patients With Meningioma: Analysis of 703 Cases
Authors: Traylor Jeffrey Isaac , Plitt Aaron , Hicks William Harrison , Mian Tabarak , Mickey Bruce E. , Lee Barnett Samuel
Published: March 2023

INTRODUCTION:

Meningioma prognostication and treatment continues to evolve with an increasing understanding of tumor biology.

METHODS:

This is a retrospective study of a consecutive series of patients with WHO grade 1–3 meningioma resected at UT Southwestern from 1994 to 2015. Time to meningioma recurrence (RFS) was the primary endpoint measured. Kaplan-Meier curves were constructed and compared using log-rank tests. Cox univariate and multivariate analyses were performed to identify predictors of RFS.

RESULTS:

A total of 703 consecutive patients with meningioma underwent resection at UT Southwestern between the years 1994 and 2015. The median age of the cohort was 56 years (range 16-88 years) and was 68.7% (n = 483) female. Median follow-up was 45 months (range 0-289 months). There was not a significantly increased risk of recurrence in patients with evidence of brain invasion, in patients with otherwise WHO grade 1 meningioma (p = .82). Adjuvant radiation to subtotally resected WHO grade 1 meningiomas did not prolong the time to recurrence. Location (midline skull base, lateral skull base, and paravenous) was significantly associated with RFS (p < .01) on univariate analysis. In patients with high grade (WHO grade 2 or 3) meningiomas, location was predictive of RFS (p = .03) with paravenous meningiomas exhibiting the highest rates of recurrence. Location was not significant on multivariate analysis.

CONCLUSIONS:

Our data suggests that brain invasion does not increase the risk of recurrence in otherwise WHO grade 1 meningioma. Adjuvant radiation to subtotally resected WHO grade 1 meningiomas did not prolong the time to recurrence. Location categorized by distinct molecular signatures did not predict RFS in a multivariate model.
192 Effect of Helmet on Cervical Spine Biomechanics in Rear Impact Scenario (Whiplash)
Authors: Choi Hoon , Purushothaman Yuvaraj , Baisden Jamie , Yoganandan Narayan
Published: March 2023

INTRODUCTION:

Rear impact (whiplash) is a common scenario has been studied previously by subjecting the head-neck complex under postero-anterior acceleration. There is a lack of studies investigating the effect of helmet on cervical spine biomechanics despite its common use in military and competitive automotive environments.

METHODS:

We developed a finite element model of the head-neck complex simulating the three spinal columns with layered intervetebral discs and ligaments. This was then validated against a cadaver (head to T1) model which was fixated to a sled on linear rails with a rear pendulum that simulated rear impact scenario. Standard-issue US Military Combat helmets in small, medium, large sizes were modeled and mounted on the finite element model. 1.8 m/s and 2.6 m/s velocity profiles were simulated and the range of motion at each functional spinal unit from C2-3 to C7-T1 was measured.

RESULTS:

Segmental motions were measured over 120 ms for all scenarios. 2.6 m/s vector resulted in peak acceleration of 3.5 g, and 1.8 m/s resulted in 2.5 g. Helmet use increased the range of motion at all segments from C2-3 to C7-T1. The greatest range of motion occurred at C5-6, followed by C6-7 and C7-T1. Greatest percentage increase in motion occurred at C2-3 followed by C5-6. Increasing helmet size resulted in increasing motion at all spinal segments.

CONCLUSIONS:

Helmet use, although protective for the cranium, significantly increases the motion at all spinal segments, especially C2-3 and C5-7, in a rear impact scenario (whiplash). Increasing helmet size results in greater motion change at all cervical spine segments. This is important to consider when designing the helmet and determining the need for additional head-mounted gear in both military and competitive automotive environments.
196 Increased Hemorrhage Risk With Brain AVM-Associated Aneurysms in Children
Authors: Lu Alex Y. , Winkler Ethan A. , Morshed Ramin , Gupta Nalin , Abla Adib Adnan
Published: March 2023

INTRODUCTION:

Brain arteriovenous malformations (AVMs) represent a major cause of intracranial hemorrhage with pediatric patients at greater lifetime risk of rupture compared to their adult counterparts. These AVMs can be associated with aneurysms that are either arterial or intranidal. The significance of AVM-associated aneurysms in the pediatric population remains poorly understood due to their rare nature and spare reporting.

METHODS:

We reviewed a prospectively maintained database of pediatric brain AVMs from 1998 to 2021 at the University of California, San Francisco. Inclusion criteria included patients with age ≤ 18 at time of presentation with angiographically-proven AVM.

RESULTS:

Of 231 patients with AVMs, 24 patients harbored 35 arterial aneurysms, and 35 patients harbored 38 intranidal aneurysms. Compared to AVMs without aneurysms with a mean nidus size of 3.02 ± 1.74 cm, AVMs with intranidal aneurysms had a significantly smaller mean nidus size at 2.13 ± 1.12 cm (p = 0.004). AVMs with intranidal aneurysms had a higher proportion of being ruptured on presentation compared to AVMs without aneurysms (94% vs. 59%, p < 0.001). AVMs with intranidal and arterial aneurysms also underwent higher proportions of surgical resection (92% and 80% vs. 59%, p = 0.001) and embolization (37% and 50% vs. 25%, p = 0.022) with higher rates of nidus obliteration (91% and 79% vs. 65%, p = 0.005). In those that were not obliterated, AVMs with intranidal and arterial aneurysms have higher annual hemorrhage risks (10.2% and 7.4% vs. 1.6%) after patient presentation. Patients who underwent a hemorrhage event after presentation had a higher proportion of worsened clinical status compared to presentation (38% vs. 5.6%, p < 0.001).

CONCLUSIONS:

A higher proportion of AVMs with associated aneurysms present with hemorrhage and are more likely to undergo additional hemorrhage events when incompletely treated compared to AVMs without aneurysms.
206 High Resolution Ultrasound for Evaluation of Peripheral Nerve Injuries: Retrospective Examination of an Emerging Technology
Authors: Xiao Tianqi , Herring Eric , Azghadi Adel , Labak Collin , Preston David , Miller Jonathan
Published: March 2023

INTRODUCTION:

Recovery from peripheral nervous system injury (PNI) after trauma has been shown to improve with earlier detection and treatment. Unfortunately, surgical treatments are usually postponed several months after injury due to the need to evaluate for potential recovery without intervention. If diagnostic modalities are able to identify which nerve injuries will require surgical intervention sooner, we may be able to significantly improve outcomes after peripheral nerve injury. High-resolution ultrasound (HRUS) is an imaging modality that potentially could provide this in an economic manner.

METHODS:

A retrospective chart review was conducted for all patients who received an HRUS of their PNI at our institution from 01/01/2020-01/31/2022.

RESULTS:

A total of 32 patients were included. The mean age was 45 years with a male predominance (69%). Neuronal and surrounding tissue pathology greater than or equal to the fascicular level could be identified with HRUS. EDx studies were available for 28 (88%) and clinical exams were available for 32 (100%) of patients. Comparing HRUS to the gold standard of a combination of clinical exam and EMG findings, HRUS had a sensitivity of 94% at identifying PNI. Ultimately, 19 (59%) of patients evaluated using HRUS underwent operative intervention.

CONCLUSIONS:

HRUS is an important emerging imaging modality that can identify and characterize PNI. Our study demonstrates the high sensitivity of HRUS in detecting PNI. Additionally, HRUS in our study identified a number of features that may serve as surrogate markers of injury useful in prognosticating recovery. Further work is needed to define the earliest time point HRUS can be used to identify a PNI.
311 A Feasibility Study for a Multicenter Phase-III Randomized Clinical Trial of Encephaloduroarteriosynagiosis Revascularization for Symptomatic Intracranial Atherosclerosis
Authors: Nisson Peyton Lubbock , Quintero-Consuegra Miguel D. , Chang Daniel , Saver Jeffrey L. , Chimowitz Marc , Gonzalez Nestor R.
Published: March 2023

INTRODUCTION:

Stroke due to intracranial-atherosclerotic-disease (ICAD) remains a major public health concern, accounting for more than one-tenth of all ischemic-strokes in the US.

METHODS:

New data from advanced cerebral imaging and angiographic studies showed that revascularization after indirect-bypass occurs earlier than appreciated before. A pilot study of EDAS in ICAD patients demonstrated angiographic neovascularization as early as 1 month. An NINDS-funded phase-II objective-performance-criterion trial demonstrated reduction in the rate of stroke and death from 21.1% in the medical group to 9.6% in the surgical group at 2 years, passing the threshold for advancement to phase III. In collaboration with the NIH-StrokeNet, a national feasibility survey was sent to sites across the country to evaluate the feasibility of a phase-III clinical trial of EDAS in ICAD.

RESULTS:

Among 72 surveys completed by prospective sites, 90% (n = 65) indicated interest in participating and 96% of these (n = 63) had neurosurgeons and anesthesiologists with sufficient experience in EDAS and cerebrovascular disorders. The mean number of direct/indirect cerebral bypass surgeries per year completed at the prospective 40 sites was 19 (Range = 10-37). StrokeNet sites cared for a median of 42.5 patients/site/year (IQR = 25-100 patients/site/year) who met enrollment criteria. With 40 participating sites, the rate of enrollment needed for successful recruitment of 516 patients in a phase-III trial is 0.28 patients/site/month (3-4 patients/year), which is an order of magnitude less than the number of relevant cases receiving care at the sites (3.54 patients/month).

CONCLUSIONS:

EDAS is a promising technique in the management of ICAD and its performance is feasible within 40 high volume institutions. Engagement of the neurosurgical community on revitalizing a surgical form of revascularization can expand the role of neurosurgery in stroke management.
314 Radiographic Risk Factors for Intracranial Hemorrhage in Patients with Left Ventricular Assist Devices
Authors: Kanter Matthew , Hernandez Nicholas , Yu-Der Wang Andy , Sharma Vaishnavi , Riesenburger Ron I. , Kryzanski James
Published: March 2023

INTRODUCTION:

Intracranial hemorrhage (ICH) in patients with left ventricular assist devices (LVAD) is a complication with significant morbidity and mortality. Many studies have identified demographic risk factors for ICH in LVAD patients; however, anatomic pre-disposition to ICH in these patients has not yet been investigated.

METHODS:

We reviewed 440 patients who received an LVAD at our institution. We then selected patients who received CT scans of the head for any reason near the time of LVAD placement. 288 patients (21 ICH, 278 Control) with CT scans were included in the analysis. A detailed chart review was then performed to collect data on patient demographics, radiographic findings, and complications.

RESULTS:

The incidence of ICH in our complete cohort was 8.6% (38/440). The presence of pump thrombosis (p = 0.001), driveline infection (p = 0.034), other hemorrhage (p = 0.001), or previous placement of a cardio-defibrillator (p = .003) during the period of LVAD implantation was associated with increased risk for ICH. An analysis of patient imaging revealed that the presence of a mass (p = 0.006), vascular malformation (p = 0.001), and microangiopathy (p = 0.04) was significantly associated with ICH in LVAD patients. We further validated the significance of these radiographic features using a multivariate logistic regression which showed that the presence of a mass (aOR 332.1, 95% CI: 14.7-7485.1, p < 0.001), vascular malformation (aOR 69.7, 95% CI: 1.8-2658.8, p = 0.022), and microangiopathy (aOR 6.5, 95% CI: 1.1-37.6, p = 0.035) were independently associated with ICH.

CONCLUSIONS:

Radiographic evidence of microangiopathy, intracranial mass, and vascular malformation are independent risk factors for ICH which may be identified at or before the time of LVAD implantation. We advocate that CT imaging may be used to further stratify patients at highest risk of ICH during treatment with an LVAD.
350 A Comparison of Incidental and Symptomatic Unruptured Brain Arteriovenous Malformations in Children
Authors: Lu Alex Y. , Winkler Ethan A. , Garcia Joseph , Raygor Kunal P. , Fullerton Heather , Fox Christine , Kim Helen , Auguste Kurtis Ian , Sun Peter P. , Hetts Steven , Lawton Michael T. , Abla Adib Adnan , Gupta Nalin
Published: March 2023

INTRODUCTION:

Unruptured brain arteriovenous malformations (AVMs) may present with headaches, seizures, and/or neurologic deficits. A smaller number of cases may be discovered incidentally. These lesions remain incompletely understood due to their sparse reporting.

METHODS:

We performed a retrospective analysis of patients presenting with brain AVMs from 1998 to 2021 at the University of California, San Francisco. Inclusion criteria included age ≤18 at time of presentation with angiographically-proven unruptured AVM diagnosed postnatally.

RESULTS:

Of 76 children with unruptured AVMs, 66 (86.8%) presented with headaches, seizures, and/or neurologic deficit. Ten (13.1%) were incidentally discovered through unrelated disease workup (50%), cranial trauma (40%), or research study participation (10%). Compared to symptomatic unruptured AVMs, incidental unruptured AVMs possessed smaller mean nidus maximum diameter (2.82 ± 1.1 vs. 3.98 ± 1.52 cm, p = 0.025) and deep venous drainage proportion (20% vs. 61%, p = 0.036). They also presented at earlier ages (10 ± 5.2 vs. 13.5 ± 4 years, p = 0.043) with longer durations to first treatment (541 ± 922 vs. 196 ± 448 days, p = 0.005). During the period of observation, one patient developed recurring headaches and demonstrated AVM nidus growth. Four AVMs greater than 3 centimeters or in deep location were treated with radiosurgery. Six other AVMs were treated with surgical resection with 2 receiving preoperative embolization. Seven AVMs (70%) were obliterated on last follow-up. Postprocedural complications included 2 transient neurologic deficits following resection and 1 delayed seizure development following radiosurgery. The mean follow-up period was 5.1 ± 5.8 years without any hemorrhage episodes.

CONCLUSIONS:

A substantial proportion of pediatric patients with unruptured AVMs are discovered incidentally. With earlier presentation and more elementary angioarchitecture than symptomatic unruptured AVMs, these incidental lesions provide a snapshot into AVM natural history before symptom development or rupture.
364 Fibrous Non-Union of Odontoid Fracture: Is it Safe to Accept Non-Operative Management? A Systematic Review
Authors: Gerstl Jakob V. E. , Kilgallon John , Riesenburger Ron I. , Florman Jeffrey
Published: March 2023

INTRODUCTION:

Non-operative management of odontoid fractures can result in solid fusion, unstable non-union and fibrous non-union. Those with fibrous non-union do not demonstrate dynamic instability on imaging but the safety of accepting this as an outcome is debatable. There are multiple reports of fibrous non-union accepted without adverse consequence however reports remain scarce and there is a lack of consensus.

METHODS:

The Pubmed and Embase databases were searched in January 2022 for terms “odontoid”, “dens”, “fracture” and “nonunion”. Outcomes were extracted and categorized according to mortality, neurologic sequelae, pain, neck disability index and satisfaction.

RESULTS:

Of a total 700 abstracts screened, 79 full texts were assessed of which 13 studies were included. A total 142 patients had a fibrous non-union, all described in observational studies. Follow-up ranged between studies ranged from 0.6 to 5.8 years. None of the 142 patients had a neurologic event. One patient had a trauma-related mortality, however causality was not exposed. The majority of studies reported good to excellent pain scores. The majority of neck disabilities reported were in the range of mild to moderate apart from one study with five patients reporting severe disability. All patients reported good or excellent satisfaction.

CONCLUSIONS:

The evidence supports it is safe to forgo surgery in carefully selected patients with non-united odontoid fractures when there is near-anatomic alignment, lack of dynamic instability on imaging, normal neurologic exam and low risk for neck injury. Further study is needed to define the full natural history of fibrous non-union of odontoid fracture.
418 Early Outcomes of the American Academy of Neurological Surgery Emerging Investigator Program in Promoting Neurosurgeon-Scientists
Authors: Srienc Anja I. , Church Sophie , Korn Stephen J. , Lonser Russell R. , Zipfel Gregory J.
Published: March 2023

INTRODUCTION:

Neurosurgeon-scientists have unique expertise to make important contributions to medicine. However, the transition from residency/fellowship training to becoming junior faculty, with the accompanying expectation of securing NIH funding, is a vulnerable period of an academic neurosurgeon’s career. The Emerging Investigator Program (EIP) is an Academy-sponsored mentorship program to support early career neurosurgeon-scientists through their transition from training to independence.

METHODS:

An analysis of the EIP was performed using demographic data provided by the EIP coordinator (author S.C.). Qualitative feedback on the program was obtained through an informal survey sent to EIP scholars (past and present) and mentors.

RESULTS:

Thirty-four scholars have participated in the EIP– fifteen have completed the program while 19 are currently participating. Eight female scholars have been accepted into the EIP (23.5%). Fifteen scholars have a PhD (44%), and 22 have had prior grant funding as residents (65%). Of the 15 EIP scholars who completed the two-year program, 10 have thus far obtained NIH funding (67%). Scholars reported the most valuable benefits of participating in the EIP were (i) feedback on grant applications and (ii) additional mentorship from outside their home institutions. Mentors reported that predictors of success included having a strong mentorship team, institutional support, and an attitude of perseverance. Scholars and mentors indicated a willingness to maintain ongoing mentor-mentee relationships outside of the sponsored EIP mentoring sessions.

CONCLUSIONS:

Scholars and mentors have had positive perceptions of the EIP. Two thirds of the program’s alumni have obtained NIH funding, suggesting early success of the EIP. Future analyses should include a more quantitative assessment of participant outcome will be pursued once more scholars have completed the program, and more detailed diversity metrics.
427 Cognitive Function and Catastrophizing in the Adult Deformity Population: Single Center Series of 111 Patients
Authors: Scheer Justin Kemp , Lui Austin , Burke John Frederick , Jedwood Chloe , Wang Albert , Wang Elaina , Catalan Tony , Chang Diana , Belfield Bethany , Thapar Isabelle Thapar , Safaee Michael , Lau Darryl , Fury Marissa , Theologis Alekos , Clark Aaron John , Ames Christopher P.
Published: March 2023

INTRODUCTION:

Baseline cognitive impairment (CI) in adult spinal deformity (ASD) pts is unknown and may affect how they report PROMs/experience pain. Goal of this study was to determine baseline CI prevalence and how it’s related to PROMs/pain catastrophizing.

METHODS:

Single center prospective study. PROMs included the Montreal Cognitive Assessment(MOCA), Pain Catastrophizing Scale (PainCS), back pain numerical score, Oswestry Disability Index(ODI), and Scoliosis Research Society-22 (SRS22) questionnaires. Pts were stratified by normal cognition (MOCA scores 26-30), mild CI (MOCA 18-25), moderate CI (MOCA 10-17) and Severe CI (MOCA <10). PainCS (higher = more catastrophizing) has total scor e(T,max = 52) and 3 subdomains (Rumination [R,max = 16], Magnification [M,max = 12], Helplessness [H,max = 24]). Comparisons were made between pts with normal (NORM) and any type of CI (CI) as well as correlations between MOCA and PROMS. MOCA scores were compared postop.

RESULTS:

Total 111 pts enrolled (mean age 64.1 ± 9.8 yrs, 57.5% F). Mean baseline MOCA score was 25.0±3.0 (mild CI, range 14-30), 59/111(53.1%) had mild/moderate CI. No severe CI. CI pts had significantly higher mean baseline PainCS-T, PainCS-R, and PainCS-M scores than NORM. CI pts had significantly worse baseline ODI (55.2 ± 15 vs 47.9 ± 14.4, p = 0.02) but better self-reported SRS Mental score (3.3 ± 1 vs 2.7 ± 0.8, p = 0.004) than NORM. Lower baseline MOCA scores significantly correlated with higher baseline ODI(r=-0.24,p=0.015), SRS Mental (r = -0.21, p = 0.037), current back pain (r = -0.26, p=0.006), and PainCS-R (r=-0.38, p<0.001), PainCS-M(r = -0.37, p < 0.001), PainCS-H (r = -0.27, p = 0.004), PainCS-T(r = -0.36, p < 0.001). Mean pre/postop MOCA scores were not significantly different (p > 0.05).

CONCLUSIONS:

Baseline CI is frequent in ASD pts and associated with higher baseline pain/disability and pain catastrophizing compared to ASD pts with normal cognition. The CI persists postoperatively.