bluuebunny/crossref_metadata_2025 huggingface dataset:
748 Utility of a Neurosurgery Sub-Internship Boot Camp in Preparing Medical Students for Neurosurgical Residency
Authors: Ng Patrick , Yearley Alexander , Gupta Saksham , Rees "Rees" Cosgrove G. , Mooney Michael Anthony
Published: March 2023

INTRODUCTION:

The neurosurgical sub-internship is a crucial step for prospective neurosurgeons. However, the expectations for sub-interns, particularly the technical skills required by residents and attendings, are often unclear. Neurosurgical skills-based workshops have been recently applied to medical students.

METHODS:

A one-day craniotomy lab using cadaveric cranial specimens was conducted for medical students. Surveys querying important competencies for sub-internships were answered by residents and attendings at affiliated hospitals. Pre- and post-lab surveys querying interest in and perceptions of neurosurgery, self-assessment of skills, and important competencies for sub-internship preparation were answered by attendees.

RESULTS:

Medical students, residents, and attendings agreed that burr hole placement, bone replating, and galea and skin closure were of high importance for sub-interns. There was significant disagreement on the importance of dural opening, dural closure, establishing a craniotomy, and neuronavigation for sub-interns. Additional competencies expected of sub-interns include minor procedures, neuroimaging, neuroanatomy, and proactive patient care. The workshop altered perceptions of neurosurgery with significant changes in recognizing the value of peer mentorship. Students also expressed increased confidence in technical skills with significant improvements in an understanding of high-speed drill use in neurosurgery (p < 0.001).

CONCLUSIONS:

Though the expectations for sub-interns may be heterogeneous, there is general agreement that proficiency in the initial and final steps of craniotomies, as well as minor procedures, is recommended. Cadaveric labs can improve student engagement in neurosurgery and enhance technical skills.
766 Use of Ventriculostomy for Severe Traumatic Brain Injury Significantly Reduces Mortality Compared to Intraparenchymal Monitor Use
Authors: Mouchtouris Nikolaos , Luck Trevor , Yudkoff Clifford , Locke Katherine , Andrews Carrie Elizabeth , Harrop James S. , Shah Syed O. , Jallo Jack
Published: March 2023

INTRODUCTION:

There is a lack of data on whether intracranial pressure (ICP)-guided therapy with an intraparenchymal fiberoptic monitor (IPM) or an external ventricular drain (EVD) leads to superior outcomes. Given the lack of consensus on whether an EVD or an IPM monitor should be preferentially used if both are feasible options, there is a pressing need to determine which modality leads to more effective ICP-guided therapy while also minimizing the procedure-related complications.

METHODS:

Retrospective analysis of severe TBI that required IPM or EVD placement for ICP-guided therapy from 1/1/2010-12/31/2020. The data was obtained from the Pennsylvania Trauma Systems Foundation (PTSF) registry.

RESULTS:

A total of 2,305 patients met the inclusion criteria with 1,048 (45.5%) IPM and 1,257 (54.5%) EVD placed. A craniectomy was performed in 47.0% of the patients in the IPM cohort and 66.0% of the EVD cohort (p < 0.001). Multivariable logistic regression analysis showed that older age (OR 1.03, p < 0.001), decreasing GCS score (OR 1.16, p < 0.001), requiring craniectomy (OR 1.22, p = 0.049), and an IPM (OR 1.40, p = 0.001) were significant predictors of mortality. Among those treated medically only, inpatient mortality occurred in 171 (30.8%) of those with an IPM and in 100 (23.4%) of those with an EVD (p = 0.010); the EVD conferred significant mortality benefit (30% decrease, p = 0.005) when controlling for age and admission GCS.

CONCLUSIONS:

The lack of consensus on whether IPM monitor or EVD is more effective leads to ambiguity in the treatment of patients with severe TBI. Our study demonstrates a significant improvement in mortality was associated with the use of EVD in comparison to IPM. This mortality benefit was seen in patients who underwent decompressive hemicraniectomy as well as those who did not.
768 The Device for Intraventricular Entry (DIVE) Guide: A Novel Solution to a Perpetual Problem
Authors: Blue Rachel , Jabarkheel Rashad , Ajmera Sonia , Tomlinson Samuel , Miranda Stephen , Schuster James M. , Spadola Michael
Published: March 2023

INTRODUCTION:

Safe and reliable access to the ventricular system is a necessary skill in the neurosurgical armamentarium. The freehand technique for catheter placement remains an accepted method, yet the inaccuracy rate can be as high as 40%, with as many as 3 passes per procedure, and complication rates between 10-40%. A number of devices have been developed to assist with catheter placement, however, these devices inhibit ergonomics or require larger incisions and expensive navigation technology.

METHODS:

A novel device for ventricular entry, the DIVE guide, was designed by the first and senior author. 50 patients undergoing extra ventricular drain (EVD) or shunt placement were prospectively enrolled for DIVE assisted catheter placement under an IRB approved study with a non-significant risk (NSR) device designation. The primary outcome is catheter location on CT. Secondary outcomes include number of catheter passes, clinically significant hemorrhages and procedure-related infections.

RESULTS:

50 patients were enrolled at a single academic center for ventricular access with DIVE assistance. Indications included subarachnoid or intraventricular hemorrhage, TBI, hydrocephalus, pseudotumor and post-surgical wound drainage. 76% (38/50) underwent right sided placement and 24% (12/20) underwent left. 100% (50/50) had successful cannulation in an average of 1.06 passes. Post procedure head CT confirmed ipsilateral frontal horn or 3rd ventricle placement (Kakarla Grade 1) in 92% (46/50) and 8% (4/50) in the contralateral lateral ventricle (Grade 2). There were no significant tract hemorrhages or procedural infections.

CONCLUSIONS:

This a prospective study to investigate the safety and efficacy of DIVE-assisted ventricular access. 100% of procedures had successful ventricular cannulation, with 92% achieving Kakarla Grade 1, in an average of 1.06 passes.
794 Interventional Approaches to Symptomatic Tarlov Cysts: a Five-year Institutional Experience
Authors: Tracz Jovanna , Judy Brendan F. , Khan Majid , Witham Timothy F.
Published: March 2023

INTRODUCTION:

Tarlov cysts are perineural collections of cerebrospinal fluid most often affecting sacral nerve roots. Up to 4.6% of the general population has one or more Tarlov cysts, with 20% of cysts becoming symptomatic, causing back pain, extremity paresthesias and weakness, bladder/bowel dysfunction, and sexual dysfunction. The most effective treatment of symptomatic Tarlov cysts, with options including nonsurgical management, cyst aspiration and injection of fibrin glue, cyst fenestration, and nerve root imbrication, is debated.

METHODS:

Retrospective chart review was conducted for 50 patients with Tarlov cysts seen at our institution in the last 5 years. Clinical outcome was determined based on improvement in one or more symptoms.

RESULTS:

36 patients with symptomatic Tarlov cysts were identified.The average age of patients with symptomatic Tarlov cysts was 55.67 years (range, 2–77). Common symptoms were back pain/sacrococcygeal (94.4%), radiculopathy (66.7%), and bladder/bowel dysfunction (33.3%). 12% of patients had underlying connective tissue disorders (CTD), 44% of patients had bilateral cysts, and 16% of patients had cysts in multiple regions. 47.2% of patients with symptomatic Tarlov cysts were managed nonsurgically; 50% were managed with CT-guided aspiration of the cyst with or without injection of fibrin glue. Of patients treated interventionally, 47.4% saw lasting clinical improvement, with the most improvement in patients after aspiration with fibrin glue injection, 10.5% saw improvement for ≥ 6 months, and 36.8% saw no improvement or temporary improvement for < 6 months.

CONCLUSIONS:

Patients with symptomatic Tarlov cysts who underwent cyst aspiration with injection of fibrin glue saw the most clinical improvement. As a significant portion of patients with Tarlov cysts have CTD, evaluation by rheumatology may be warranted.
803 Outcome Analysis of Surgical Management of Paediatric Cervical Kyphotic Deformity (CKD): An Institutional Experience
Authors: Kumarasamy Sivaraman , Sawarkar Dattaraja , Kumar Rajinder , Chandra Sarat P. , Kale Shashank S. , Singh Pankaj Kumar
Published: March 2023

INTRODUCTION:

Paediatric cervical kyphotic deformity (CKD) is extremely rare and occurs due to congenital, traumatic, metabolic or neoplastic processes which mandates surgical correction. Most outcomes analysis following surgery are small retrospective case series and are limited to specific etiology or surgical technique.

METHODS:

Patients (aged ≤ 18 years) operated at a tertiary centre between January 2009 to April 2022 were included. Besides demographic details, the outcome measures assessed were clinical (Nurick grading, mJOA score), radiological (Cobb’s angle) and operative complications.

RESULTS:

A total of twenty-two patients were included, with mean age of 12.90 4.02 years (3 – 18) of which ten were syndromic, three were metabolic, seven were post-traumatic and one post-infective. Thirteen patient had features of myelopathy on presentation. All underwent surgical correction, of which nine patients underwent Antero-posterior approach, eight patients underwent Posterior only approach and four patients underwent Anterior only approach. Clinically, patients improved postoperatively with – Nurick grade (pre vs. post: 3.24 vs. 2.24, p – 0.172), mJOA score (pre vs. post: 10.19 vs. 12.71, p – 0.679). There was significant deformity correction from 37.086° to 13.725° (p – 0.045). Mean blood loss encountered was 680 ± 671.93 cc. Early complications included intraoperative hemodynamic instability (4) and lung collapse (1). Late complications included junctional kyphosis (1). Mean follow-up was 49.38 ± 44.15 months.

CONCLUSIONS:

Pediatric CKD are rare, debilitating condition which can be managed surgically. Antero-posterior approach provides circumferential decompression and better correction compared to Anterior only and posterior only approach. Patients should be screened for syndromic association and regularly followed.
807 Outcomes of Endovascular Embolization for Vein of Galen Malformations: An Individual Participant Data Meta-Analysis
Authors: Hale Andrew T. , Savage Cody , Parr Matthew Saifi , Hedaya Alexander , Saccomano Benjamin , Tsema Georges Bouobda , Hafeez Muhammad , Tanweer Omar , Kan Peter , Solomon Laurent , Deloison Benjamin , Meila Dan , Blount Jeffrey P. , Johnston James M. , Rocque Brandon George , Rozzelle Curtis J. , Bhatia Kartik , Muthusami Prakash , Krings Timo , Jones Jesse
Published: March 2023

INTRODUCTION:

Understanding outcomes of Vein of Galen malformation (VOGM) embolization have been limited by small sample size and heterogeneity of reported series.

METHODS:

We performed a systematic review and individual patient data meta-analysis of VOGM endovascular outcomes according to PRISMA guidelines. Individual patient data (IPD) including demographic, intra/post-operative complications, treatment efficacy (partial or complete occlusion), and neurological outcome were collected. Mixed-effects logistic regression with random effects modeling and Bonferroni correction was used (p<0.003 threshold for statistical significance). The primary and secondary outcomes were all-cause mortality and poor clinical outcome (moderate/severe developmental delay or permanent disabling injury), respectively.

RESULTS:

Thirty-five studies totaling 307 patients evaluating outcomes of endovascular embolization for VOGM were included. Mean follow up was 42 (±57) months. Our analysis contained 42% neonates (<1 month) at first embolization, 45% infants (1 month < 2 years), and 13% children (>2 years). Complete occlusion was obtained in 48% of patients. Overall all-cause mortality was 16%. Overall, good clinical outcome was achieved in 68% of patients. First embolization as a neonate (OR = 6.93 [1.99-24.08] p<0.001) and incomplete occlusion (OR = 10.87 [1.86-63.55], p < 0.001) were associated with mortality. First embolization as a neonate (OR = 3.24 [1.47-7.15], p < 0.001), incomplete occlusion (OR = 5.26 [2.06-13.43], p < 0.001), and heart failure at presentation (OR = 3.10 [1.03-9.33], p = 0.002) were associated with poor clinical outcomes. Sex, angioarchitecture of lesion, embolization technique, and single or multistage embolization were not associated with mortality or clinical outcome.

CONCLUSIONS:

For the first time, we identify incomplete embolization treatment associated with poor clinical outcome and mortality. While this study provides the highest level of evidence for VOGM embolization to date, prospective multicenter studies are needed to understand the optimal treatment strategies, outcomes, and natural history after VOGM embolization.
827 The Use of High Resolution Ultrasound in the Evaluation of Traumatic Peripheral Nerve Injury: A Systematic Literature Review
Authors: Braverman Aaron , Shi Shi , Herring Eric , Labak Collin , Azghadi Adel , Preston David , Miller Jonathan
Published: March 2023

INTRODUCTION:

Traumatic peripheral nerve injury (TPNI) represents a heterogeneous pathology with potential for severe disability. High-resolution ultrasound (HRU) has potential as a non-invasive diagnostic tool to assess injury and inform management decisions, potentially at an earlier time point than traditional electrodiagnostic testing. Standardized assessment of TPNI using HRU is not available in the current literature. We aimed to evaluate the effectiveness of pre-operative HRU in the setting of TPNI through a literature review.

METHODS:

A systematic literature review was performed adhering to PRISMA guidelines, yielding 84 articles for review. Inclusion criteria included papers that examined ballistic, sharp, and avulsion etiologies of TPNI, and that used ultrasound for initial evaluation of the TPNI. Exclusion criteria included papers with primarily pediatric patients, reviews, meta-analyses, papers not in English, and papers that focused on iatrogenic PNIs.

RESULTS:

48 studies met inclusion and exclusion criteria, including 19 case studies, 8 retrospective studies, and 19 prospective studies describing 569 total patients who experienced TPNI. Mean age was 33 years. The studies characterized 121 median, 97 ulnar, 141 radial, and 222 other TPNI from 24 ballistic, 231 sharp, 78 avulsion, and 13 unspecified injuries. The most common HRU findings preoperatively were neuroma formation (79), fascicular swelling (141), and complete discontinuity of epineurium (155). The timing of HRU after TPNI was variable with 37% and 41% of patients undergoing HRU within 6 weeks after TPNI versus more than 6 weeks after TPNI respectively.

CONCLUSIONS:

HRU is a promising clinical tool for the evaluation of TPNI. Further work is needed to define the appropriate timing for when HRU can be used to evaluate TPNI, as well as radiographic findings that may be clinically relevant in operative evaluations.
837 Responsive Neurostimulation of the Thalamus for the Treatment of Refractory Epilepsy
Authors: Roa Jorge A. , Abramova Marina , Madeline  , La Vega-Talbott Maite , Wolf Steven , Yoo Jiyeoun , Marcuse Lara , Ghatan Saadi , Panov Fedor
Published: March 2023

INTRODUCTION:

One-third of patients with epilepsy experience seizures despite antiepileptic medications. Some of these refractory patients may not be candidates for surgical resection. The Responsive Neurostimulation System (RNS) is a closed-loop device that uses programmable detection and stimulation.

METHODS:

We performed a prospective single-center study of consecutive refractory epilepsy patients who underwent RNS system implantation in the anterior (ANT) and centromedian (CM) thalamic nuclei from September 2015 to December 2020. Patients were followed postoperatively to evaluate seizure freedom and complications.

RESULTS:

Twenty-three patients underwent placement of 36 RNS thalamic leads (CM = 27 leads, ANT = 9 leads). Mean age at implant was 18.8 ± 11.2 years. Two patients (8.7%) developed infections: 1 improved with antibiotic treatments alone, and 1 required removal with eventual replacement of the system. Mean follow-up was 22.3 months. Based on overall reduction of seizure frequency, 2 patients (8.7%) had no- to <25% improvement, 6 patients (26.1%) had 25-49% improvement, 14 patients (60.9%) had 50-99% improvement, and 1 patient (4.3%) became seizure-free. All patients reported significant improvement in seizure duration and severity, and 17 patients (74%) reported improved post-ictal state. There was a trend for subjects with foci located in the temporal lobe to achieve better outcomes after thalamic RNS compared to those with extratemporal foci. Seizure etiology was syndromic in 12 cases (52.2%).

CONCLUSIONS:

Thalamic RNS achieved ≥50% seizure control in ∼65% of patients. Infections were the most common complication. This therapeutic modality may be particularly useful for patients affected by aggressive epilepsy syndromes since a young age, those whose seizure foci are located in the mesial temporal lobe, and those who have failed prior surgical interventions.
838 Gamma Knife Stereotactic Radiosurgery Retreatment of Trigeminal Neuralgia: Prognostic Factors and Clinical Outcomes
Authors: Ramanathan Siddharth , Loving Bailey , Fontanesi James , Grills Inga S. , Michael Daniel B. , Chen Peter , Fahim Daniel K.
Published: March 2023

INTRODUCTION:

Trigeminal neuralgia(TN) is a debilitating nerve disorder affecting approximately 4.5 per 100,000 people annually. While medical management is the first line of treatment, Gamma Knife Stereotactic Radiosurgery(GKSRS) may be used. Long-term outcomes after GKSRS retreatment are not well elucidated.

METHODS:

Of the 168 patients treated since 2012 at our institution, 149 had adequate follow-up data, and 53(40.4%) received 2 treatments. The Barrow Neurological Institute (BNI) pain intensity score was used to grade pain. Pain relief was defined as post-GKSRS BNI score of I-III. Treatment failure was defined as post-GKSRS score of IV-V without pain-relief. Pain-recurrence was defined as a post-GKSRS score of IV-V after achieving pain-relief. Univariable analyses were performed to examine the effects of multiple factors on outcomes.

RESULTS:

Median follow-up was 15(1-63) months; 136(90%) and 49(83.0%) patients achieved pain-relief after T1 and T2 respectively. Median time to pain-relief was 3 months and 1 month after T1 and T2 respectively. Median freedom from pain-recurrence was 24.0 months and 13.7 months following T1 and T2 respectively; 44 (30.0%) and 6 (12.2%) patients developed pain-recurrence following T1 and T2 respectively. High KPS score, V1+V2 pain distribution, and absence of mastication deficits reduced the risk of T1 treatment failure by 21%, 58%, and 54% respectively(p<0.05). Patients with lower BNI scores after T1 had a 39% reduced risk of T2 failure(p<0.001); 2(1.3%) and 4(6.8%) patients developed facial and/or mastication deficits following T1 and T2 respectively. Neither isocenter location nor dose affected outcomes.

CONCLUSIONS:

GKSRS remains an effective treatment for patients with refractory TN. Our data show that patients who fail or recur after T1 may still receive symptomatic relief following T2 with minimal toxicity. Abstract not yet presented, but accepted for presentation at ASTRO 2022
869 Loss to Follow-Up for Radiation Treatment After Resection of Metastatic Brain Tumors: Analysis of a Non-Irradiated Cohort from a Private Insurance Database
Authors: Haider Ghani , Amoah Dadey David Yaw , Rodrigues Adrian , Pollom Erqi , Adler John R. , Veeravagu Anand
Published: March 2023

INTRODUCTION:

Radiation treatment to the surgical bed of resected brain metastases is considered the standard of care due to its advantages in improving local and distant disease control. Overtime, SRS has replaced WBRT as the preferred modality due to preservation of long-term neuro-cognition. Despite this data and growing adoption, socio-economic disparities in clinical access, treatment and outcomes have been reported in minority groups, especially in oncologic patients – leading to sub-standard care for some patient populations.

METHODS:

Our sample was obtained from Optum Commercial Claims and Encounters Database and included all patients from 2004 to 2021 who did not receive SRS or WBRT within sixty days after resection of tumors metastatic to the brain. Regression analysis was done to identify factors responsible for loss to adjuvant radiation treatment.

RESULTS:

A total of 8,362 patinets were identified who had undergone craniotomy for resection of metastatic brain tumors, of which 3,430 (41%) patients did not receive any radiation treatment. Lung cancer, breast cancer, melanoma and colon cancer were the most common sites of primary tumor. Compared to patients who did receive some form of radiation treatment (SRS or WRBT), patients who did not get any form of radiation were more likely to be older (P = 0.0189), and non-white (P = 0.008). Patients with Elixhauser Comorbidity Index ≥3 were less likely to receive radiation treatment (P < 0.01). Fewer patients with household income ≥ $75,000 did not receive radiation treatment (P < 0.01).

CONCLUSIONS:

Age, race, household income and comorbidity status were associated with differential likelihood to receive radiation treatment. This highlights the need for additional investigation of socio-economic determinants of radiation treatment delivery.
873 Next Generation Sequencing of Gliomas to Identify Predictors of Postoperative Seizures
Authors: Nguyen Minh P. , Shukla Poojan , Young Jacob , Lee Anthony T. , Chang Edward
Published: March 2023

INTRODUCTION:

Seizures are common in patients who have undergone resection of diffuse gliomas. As genetic characterization of gliomas has improved, how a tumors mutational profile influences the risk of postoperative epileptogenesis is currently unknown.

METHODS:

A retrospective review of patients who underwent resection of gliomas with next generation sequencing of tumors at a single institution was performed. Logistic regression, Fisher’s Exact Test, and linear regression were performed to identify factors associated with development of postoperative seizures, seizure frequency, seizure type, and number of antiepileptic drugs (AEDs).

RESULTS:

140 patients with tumor tissue genotyped via next generation sequencing from 2017-2020 are included in this interim analysis (this cohort includes both newly diagnosed and recurrent tumors). Glioblastomas comprised the majority (59.3%) of tumors, followed by astrocytomas (18.6%), oligodendrogliomas (13,6%), and IDH-mutant diffuse gliomas (8.6%). Fifty-two (37.1%) patients had a seizure after tumor resection, median age at seizure onset was 56.5 years, and patients were on a median of 2 AEDs for their seizures. 75.0% of these patients experienced multiple seizures with 57.1% being simple partial seizures. Multivariate analysis of the most common mutations revealed that CDKN2B/CDKN2A mutation was significantly associated with postoperative seizures (OR 2.47, 95% CI 1.02 – 6.27, p = 0.0487), while NF1 mutation and 1p/19q codeletion were not. The common GBM copy number variant Polysomy 7/monosomy 10 was associated with use of fewer AEDs (β = -0.81, p <0.0001). Analysis of mutations most common in low grade tumor samples found no significant associations with seizure development.

CONCLUSIONS:

CDKN2B/CDKN2A mutations are associated with more postoperative seizures. Further analysis of this cohort may yield more relationships between genetic markers and seizures, including time to onset of seizures, which can inform operative planning and postoperative management.
876 Significant Survival Improvements for Patients with Melanoma Brain Metastases: Can We Reach Cure in the Current Era?
Authors: Berger Assaf , Bernstein Kenneth , AlzateRamirez Juan , Mullen Reed , Silverman Joshua S. , Sulman Erik P. , Donahue Bernadine , Anna Pavlick , Gurewitz Jason , Mureb Monica , Mehnert Janice , Madden Kathleen , Palermo Amy , Weber Jeffrey , Golfinos John G. , Kondziolka Douglas
Published: March 2023

INTRODUCTION:

New therapies for melanoma have been associated with increasing survival expectations, as opposed to the dismal outcomes of only a decade ago.

METHODS:

We reviewed 171 melanoma patients with BM receiving stereotactic radiosurgery (SRS) who were followed with point-of-care data collection between 2012-2020. Clinical, molecular and imaging data were collected, including systemic treatment and radiosurgical parameters.

RESULTS:

Mean age was 63 ± 15 years, 39% were female and 29% had BRAF-mutated tumors. Median overall survival after radiosurgery was 15.7 months (95% Confidence Interval: 11.4-27.7) and 25 months in patients managed since 2015. Thirty-two patients survived 5 years from their initial SRS. BRAF mutation-targeted therapies showed a survival advantage in comparison to chemotherapy (p = 0.009), but not to immunotherapy (p = 0.09). In a multivariable analysis, both immunotherapy and the number of metastases at 1st SRS were predictors of long-term survival (5 years) from initial SRS (p = 0.023 and p = 0.018, respectively). Five patients (16%) of the long-term survivors required no active treatment for 5 years.

CONCLUSIONS:

Long-term survival in patients with melanoma BM is achievable in the current era of SRS combined with immunotherapies. For those alive 5 years after first SRS, 16% had been also off systemic or local brain therapy for over 5 years. Given late recurrences of melanoma, caution is warranted, however prolonged survival off active treatment in a subset of our patients raises the potential for cure.
885 Reprogramming the Glioblastoma Immune Microenvironment With Convection Enhanced Gene Therapy Reveals Intratumor IL6 Drives Glioblastoma Immunosuppression and Growth
Authors: Young Jacob , Cho Nam Woo , Lucas Calixto-Hope , Seo Kyounghee , Santos Raquel , Liu S. John , Phillips Joanna , Ozawa Tomoko , Bhaduri Aparna , Aghi Manish Kumar , Berger Mitchel , Raleigh David R.
Published: March 2023

INTRODUCTION:

The glioblastoma microenvironment is an immunosuppressive barrier to therapeutic innovation.

METHODS:

SB28 or GL261 glioblastoma allografts were implanted into immunocompetent mice and treated with CED of attenuated adeno-associated virus 9 vectors (AAV9) encoding experimental cytokines (Il1b, Ccl4, or Apoa1) underlying infiltration or activation of anti-tumor immune cells in other intracranial tumors. Serial intracranial bioluminescence was used to assess glioblastoma growth and animals were monitored for survival. The impact of gene therapy perturbations on the glioblastoma immune microenvironment was assessed using histology, immunohistochemistry, single-cell mass cytometry (CyTOF), and multiplexed cytokine assays.

RESULTS:

Serial body weight and systemic multiplexed cytokine measurements showed no evidence of treatment toxicity. AAV9-APOA1 or AAV9-IL1B gene therapy CED treatments attenuated SB28 growth and prolonged survival, decreasing immunosuppressive macrophage infiltration and increasing CD8 T cell and microglia infiltration of the glioblastoma microenvironment compared to control AAV9 vectors. Gene therapy CED treatments did not attenuate GL261 growth or prolong survival, but CyTOF of human glioblastomas (n = 6) in comparison to preclinical models revealed untreated GL261 glioblastomas were endogenously enriched in CD8 T cells and other lymphoid lineages compared to untreated SB28 or human glioblastomas. Multiplexed cytokine assays demonstrated suppression of intratumor IL6 is a conserved mechanism of action underlying glioblastoma gene therapy responses. Analysis of single-cell RNA sequencing of 32,877 cells from human glioblastomas (n = 11) showed IL6 is predominantly produced by radial glial like cancer stem cells or endothelial cells in the tumor microenvironment. In support of these findings, survival from intracranial SB28 glioblastomas was prolonged in Il6 knockout C57BL/6J mice compared to wildtype C57BL/6J mice.

CONCLUSIONS:

We report a novel strategy using gene therapy and CED to reprogram the glioblastoma immune microenvironment, revealing IL6 drives glioblastoma immunosuppression and growth.
Ontogenetic exposure to light influences seabird vulnerability to light pollution
Authors: Atchoi Elizabeth , Mitkus Mindaugas , Vitta Pranciškus , Machado Biana , Rocha Margarida , Juliano Manuela , Bried Joël , Rodríguez Airam
Published: March 2023

Light pollution critically affects fledglings of burrow-nesting seabirds, leading to massive mortality events. The successful management of this pollutant depends upon a comprehensive understanding of the factors influencing visual sensitivity and corresponding behaviours towards light. Factors shaping the development of the visual system could account for variation in seabirds' vulnerability to light pollution. We investigated how Cory's shearwater chicks respond to selected contrasting artificial light stimuli. Chicks were subjected to blue and red light treatments, and repeatedly tested throughout the nestling period. We analysed behavioural responses (number, timing and orientation of reactions) to determine how age, exposure to experimental light stimuli and spectra influenced the onset of visually guided behaviours, thus inferring drivers of vulnerability to light pollution. Repetitive exposure to light significantly increased the number of reactions, and chicks predominantly displayed light avoidance behaviour. We did not find differences in the number of reactions, timing and orientation between blue and red light treatments. The responses did not differ across different age groups. These results provide empirical evidence for the contribution of the light available in the rearing environment to seabird visual development. They support the hypothesis that differential exposure to light during the growth period influences responses to artificial light, and that the state of visual development at fledging could be a main driver of the age bias observed during seabird fallout events. It is thus important to evaluate lighting schemes in both urban and natural areas, and determine the as yet unknown consequences that may be affecting the populations.
Development and Pilot Testing of a Telehealth Weight Loss Program
Authors: Hales Sarah B. , Smith Caitlin E. , Turner Tonya F. , Sword David O. , DuBose-Morris Ragan , Blackburn David , Malcolm Robert , O’Neil Patrick M.
Published: March 2023

Introduction/Purpose

Behaviorally based in-person multidisciplinary programs for weight loss have been studied for decades; however, delivery, scalability, and accessibility remain a challenge. We report pilot findings from a new asynchronous protocol-based telehealth weight loss program.

Methods

This 12-wk single-arm pilot study included adults (18–65 yr old) with body mass index (BMI) of 25–40 kg·m−2. The Home Weight Loss (HWL) program consisted of weekly app- and e-mail-delivered lesson modules covering traditional diet, exercise, and behavioral topics for weight loss. Daily weight and activity level were monitored automatically via a wireless scale and an activity tracker, and participants logged their caloric intake into the system. Monitoring data were reviewed weekly by clinicians who provided brief video-recorded feedback for participants to view at their convenience. Weight and height were measured in person at baseline and postintervention. Postintervention participants completed a satisfaction survey.

Results

Thirty participants (70% female; 80% White; mean age = 41 yr, standard deviation (SD) = 13.7 yr; mean BMI = 32.4 kg·m−2, SD = 4.3 kg·m−2) were enrolled, and 27 provided posttreatment data. Percent weight loss was 4.12% (SD = 4.22%). Overall, 93% of participants reported being satisfied with their overall experience in the program, and 59% cited individualized feedback as a benefit of the program.

Conclusions

The HWL program produced modest weight loss and demonstrated feasibility and participant acceptability. This model appears to be generally scalable for broader use and can be used to extend weight loss services for those not residing near medical centers and those in need of asynchronous and virtual feedback.
The complete mitochondrial genome Hainan Gymnure Neohylomys hainanensis
Authors: Tu Feiyun , Hou Xiaodan , Lu Qiujie , Zhai Xiaofei
Published: March 2023

The Hainan Gymnure Neohylomys hainanensis is a small-size mammal which occurs in Hainan, China and north Vietnam. Here, we report the complete mitochondrial genome of N. hainanensis. The whole mitochondrial genome is 17,337 bp, and contains 13 protein-coding genes, 22 tRNAs, 2 rRNAs and one control region. The base composition of the N. hainanensis total mitogenome is: 33.4% A, 12.2% G, 33.1% T, and C 21.3%, with an A + T content of 66.5%. The K2P genetic distance analysis supports current taxonomy that places the hainanensis, sinensis and suillus in different genera. Phylogenetic analysis suggests that N. hainanensis is closely related to Neotetracus sinensis based on the complete mitochondrial genome sequences. The mitogenomic data will contribute to molecular phylogenetics and conservation genetics of the species.
Current and future opportunities of autodissemination of pyriproxyfen approach for malaria vector control in urban and rural Africa
Authors: Mmbaga Augustino Thabiti , Lwetoijera Dickson Wilson
Published: March 2023

Despite the progress made in reducing malaria burden, new ways to address the increasing challenges of insecticide resistance and the invasion and spread of exotic malaria vectors such as Anopheles stephensi in Africa are urgently needed. While African countries are adopting larviciding as a complementary intervention for malaria vector control, the autodissemination technology has the potential to overcome barriers associated with the identification and treatment of prolific habitats that impede conventional larviciding approaches in rural settings. The autodissemination technology as a “lure and release” strategy works by exploiting the resting behavior of gravid mosquitoes to transfer lethal concentration of biological or chemical insecticide such as pyriproxyfen (PPF), an insect growth regulator (IGRs) to their oviposition sites and result in adult emergence.

Despite the evidence of the autodissemination approach to control other mosquito-borne diseases, there is growing and promising evidence for its use in controlling malaria vectors in Africa, which highlights the momentous research that needs to be sustained. This article reviews the evidence for efficacy of the autodissemination approach using PPF and discusses its potential as efficient and affordable complementary malaria vector control intervention in Africa. In the previous studies that were done in controlled semi-field environments, autodissemination with PPF demonstrated its potential in reducing densities of captive population of malaria vectors such as Anopheles gambiae and Anopheles arabiensis. Of importance, empirical evidence and biology-informed mathematical models to demonstrate the utility of the autodissemination approach to control wild populations of malaria vectors under field environment either alone or in combination with other tools are underway. Among others, the key determining factors for future introduction of this approach at scale is having scalable autodissemination devices, optimized PPF formulations, assess its integration/complementarity to existing conventional larviciding, and community perception and acceptance of the autodissemination approach.
ASSESSING LEADERSHIP EDUCATION IN THREE INSTRUCTIONAL MODALITIES: LESSONS LEARNED
Authors: Bourgeois Jeff , Klaus Kaley , McRay Jeni
Published: March 2023

Student learning outcomes assessment, when done right, is an ongoing and systematic process. Faculty and staff for leadership education programs often struggle to develop a comprehensive approach to assess the effectiveness of their programs, especially when those programs are offered through multiple modes of instruction. One department at a Midwestern public university has developed a thorough, five-stage process which any leadership education program can follow, regardless of size or method of delivery. This department considers three modes of instruction, including face-to-face on a traditional American campus, asynchronous online, and face-to-face at foreign universities via international partnerships. This manuscript describes the comprehensive process and offers readers considerations for implementation at their own institution.
WHAT WOULD DOLLY DO?: Dolly Parton as Authentic Leader
Authors: Raffo Deana M. , Heath Heather A.
Published: March 2023

While Dolly Parton may be best known for her distinguished music career, her philanthropic and community work is equally impressive. This paper explains how Parton’s work in these areas can illustrate the principles of authentic leadership from a popular media perspective. Parton’s popularity and wide range of fans across generations and demographics make a case study of her work a poignant and effective pedagogical tool as an introduction to authentic leadership. We share an array of resources in popular media that includes videos, podcasts, and popular press articles and offer questions to facilitate class discussion and about the qualities of an authentic leader.
INTERDISCIPLINARY LEADERSHIP: A Leadership Development Model for Scholar-Practitioners
Authors: Bloomquist Candace D. , Georges Leah
Published: March 2023

Leadership scholar-practitioners seldom need to be sold on the benefits of working together. Rather leadership educators want to know how to teach adult leadership scholar-practitioners how to work together across differences. The aim of this paper is to guide leadership development practitioners on how to nurture leadership that can address the complex problems the changing global arena demand of us today and into the future. We argue when preparing adult leadership scholar-practitioners, using adult learning theories and paying attention to the interdisciplinary roots of the field of leadership might lead to better learning and engagement with real world challenges. In this paper we present a leadership development model we call interdisciplinary leadership. First, we discuss the interdisciplinary roots of leadership. Second, we describe interdisciplinary leadership as a tapestry – an intricate combination of identities, practices, and outcomes used to prepare people to address complex problems. Finally, we describe the mission, structure, curriculum, and instructional strategies that can be used by leadership educators when applying interdisciplinary leadership. This model acknowledges the identity, practices, and outcomes needed to develop scholar-practitioners of leadership and provides practical techniques to help leadership educators prepare leaders to work together across differences to address complex problems.
Financial Covenants and Fire Sales in Closed-End Funds
Authors: Kundu Shohini
Published: March 2023

Closed-end funds are thought to have negligible fire sale risk as they have stable funding. However, I show that embedded covenants can generate price pressure in collateralized loan obligation (CLO) funds, even though such funds are closed end. Loans held by constrained CLOs report significantly lower cumulative returns than loans held by unconstrained CLOs. This can be explained by contractual arbitrage, a practice by which CLOs exploit loopholes in the design of covenants to mechanically loosen their covenants and avoid covenant breaches. Covenant breaches are associated with significant pecuniary and nonpecuniary costs, affecting CLO compensation, reputation, and career prospects. I show that when covenants breaches are imminent, managers fire sell distressed loans. Hence, I demonstrate a channel by which closed-end funds can also create fire sale risk, akin to their open-end counterparts.

This paper was accepted by Lukas Schmid, finance.

Funding: This research was funded by the John and Serena Liew Fellowship Fund at the Fama-Miller Center for Research in Finance at the University of Chicago Booth School of Business, the University of Chicago PhD Program Office, the Stigler Center for the Study of the Economy and State, and the University of Chicago Library.

Supplemental Material: The data files and online appendices are available at https://doi.org/10.1287/mnsc.2023.4708 .
Gingival enlargement among the paediatric population: an overview and case report
Authors: Bhandal Sabrina , McKaig Sarah , McGoldrick David
Published: March 2023

Patients often present with complaints of ‘bleeding and inflamed gums’, which is most frequently indicative of plaque-induced gingivitis. However, bleeding and gingival enlargement can be associated with local and systemic factors and, in some cases, be indicative of malignancy. An 18-month-old boy attended an emergency department with a 4-day history of unexplained bleeding from the gingivae. Intra-oral examination, revealed generalized enlargement of the maxillary gingivae. The gingivae were pink with loss of stippling and a spongy appearance. Following blood tests, the child was diagnosed with acute myeloid leukaemia (AML).

CPD/Clinical Relevance: An awareness of acute leukaemia is important as oral lesions can be the earliest clinical feature and dentists may be the first to see a patient.
Maintain Access Strip Technique (MAST) crown: a novel technique to stabilize anterior teeth while maintaining pulp canal access
Authors: Donovan W , Crummey A , Wright G
Published: March 2023

The management of an anterior tooth that has undergone breakdown, either due to trauma or failure of previous restorations, poses a challenge for clinicians to restore in situations where endodontic treatment is also necessary. The novel technique described in this Technique Tip: Maintain Access Strip Technique (MAST) crown, allows clinicians to effectively restore function and aesthetic form to an anterior tooth, while maintaining ease of access to the pulpal anatomy for future endodontic treatment. The approach uses clear strip crowns to reproduce coronal structure and anatomy with gutta percha cones for canal projection to maintain a path to the endodontic space.

CPD/Clinical Relevance: The MAST crown technique facilitates stabilization of traumatized or broken teeth and maintain ease of access to the root canal.
Sustainable development
Authors: Chriscoli Lucia
Published: March 2023

There is still a lack of education for sustainable development in England. Here Lucia discusses the importance of supporting children's sustainable development and creating a culture of shared sustainable values within their lives.
COVID-19 – the impact on babies and their families
Authors: Johnson Louisa
Published: March 2023

Part three of the series by Louisa Johnson investigating the impact that the COVID-19 pandemic had on families with babies reports on the research of labour experiences and how COVID may have impacted babies post birth.
Mother's experiences of weaning
Authors: Hewison Ruthie
Published: March 2023

This month Ruth Hewison shares an introduction into her research which is an exploration into mothers' experiences of the first four weeks of weaning.
Facilitating Reflection Using Experiential Learning Cycle During Community-Based Education Program
Authors: Pradnya Matilda Stella , Claramita Mora , Emilia Ova
Published: March 2023

Reflective learning in community-based education (CBE) activities requires the role of a supervisor. The ‘intensive supervision’ based on Kolb's experiential learning can provide guidance for facilitating reflection on CBE experiences through discussion. Accordingly, supervisors must receive training on providing constructive feedback sessions to assist students in reflecting. This study aimed to determine the effect of training on facilitating reflection using experiential learning methods based on the concept of 'intensive supervision' for CBE supervisors. The study design used a training program evaluation with the Kirkpatrick model of levels 1 and 2. The training on facilitating reflection was divided into workshops and mentoring sessions based on the experiential learning cycle. The questionnaire was developed to assess tutoring performance before and after the training based on the perceptions of supervisors (n=10) and students (n=43) and observers' observations during the supervisor tutoring. Descriptive and comparative data analyses were employed. The trainees showed positive reactions to the training. The students’ and supervisors’ perception questionnaires showed a significant difference in the performance of the supervisors who were assessed before and after training. Our results indicated that most of the supervisors’ ability to facilitate reflection changed following the ‘intensive supervision' method. This training helps supervisors learn how to become facilitators and students to feel more assisted in the learning process.
Use of cast immobilization versus removable brace in adults with an ankle fracture: two-year follow-up of a multicentre randomized controlled trial
Authors: Haque Aminul , Parsons Helen , Parsons Nick , Costa Matthew L. , Redmond Anthony C. , Mason James , Nwankwo Henry , Kearney Rebecca S.
Published: March 2023

Aims

The aim of this study was to compare the longer-term outcomes of operatively and nonoperatively managed patients treated with a removable brace (fixed-angle removable orthosis) or a plaster cast immobilization for an acute ankle fracture.

Methods

This is a secondary analysis of a multicentre randomized controlled trial comparing adults with an acute ankle fracture, initially managed either by operative or nonoperative care. Patients were randomly allocated to receive either a cast immobilization or a fixed-angle removable orthosis (removable brace). Data were collected on baseline characteristics, ankle function, quality of life, and complications. The Olerud-Molander Ankle Score (OMAS) was the primary outcome which was used to measure the participant’s ankle function. The primary endpoint was at 16 weeks, with longer-term follow-up at 24 weeks and two years.

Results

Overall, 436 patients (65%) completed the final two-year follow-up. The mean difference in OMAS at two years was -0.3 points favouring the plaster cast (95% confidence interval -3.9 to 3.4), indicating no statistically significant difference between the interventions. There was no evidence of differences in patient quality of life (measured using the EuroQol five-dimension five-level questionnaire) or Disability Rating Index.

Conclusion

This study demonstrated that patients treated with a removable brace had similar outcomes to those treated with a plaster cast in the first two years after injury. A removable brace is an effective alternative to traditional immobilization in a plaster cast for patients with an ankle fracture.

Cite this article: Bone Joint J 2023;105-B(4):382–388.
Effect of Simulated Refrigerated Distribution Environment on the Quality of Green Lettuce and Ground Meat
Authors: Kang Hun-Seok , Chun Ji-Yeon
Published: March 2023

This study investigated the effect of the simulated refrigerated distribution environment on the quality characteristics of green lettuce and ground meat. The simulated refrigerated distribution conditions were as follows: (A) the door was not opened while storing the product in the refrigerator, (B) the door was opened for 20 s every 10 min, and (C) the door was opened for 1 min every 10 min (C). In A, B, and C conditions, the bottom temperature was higher, and the average temperature and temperature deviation of the inside of the packaging box, green lettuce, and ground meat increased according to door opening time. According to simulated refrigerated distribution conditions, food qualities such as browning index, total chlorophyll content, and vitamin C content in green lettuce, moisture content, water holding capacity, and volatile basic nitrogen in ground meat were changed.