bluuebunny/crossref_metadata_2025 huggingface dataset:
Optimizing the transfusion strategy in surgical patients in a Lebanese university hospital
Authors: El Hawat Stephanie , Saliby Rita , Sleilaty Ghassan , El Asmar Alain , Ghosn Anthony
Published: March 2024

Background and purpose

Our aim was to analyze factors that influence transfusion requirements in surgical patients in order to achieve a transfusion-saving strategy.

Methods

Data was collected from patient’s files at the Notre Dame de Secours-Jbeil University Hospital Center between January 2017 and June 2019. Selection was made for 400 patients who had undergone surgery and required transfusion. The studied variables were age, sex, and type of surgery whether planned or urgent with its expected level of bleeding. The presence of chronic anemia, coronary artery disease, values of hemoglobin and hematocrit before and after transfusion, iron status preoperatively, and post-operation complications were also noted.

Results

The analysis of 400 transfused surgical patients showed that the mean age was 62 ± 18 years with 52.5% women and 47.5% men. In 82.3% of patients, surgical bleeding was expected, 77.8% of surgeries were scheduled, and 22.3% were urgent. Fifty-two percent of patients were known to have coronary artery disease. Orthopedic (35%) and cardiothoracic (29.5%) surgeries had the highest transfusion rate.

Among all patients, only 106 patients (26.5%) underwent a preoperative iron workup. The pre-transfusion levels of hemoglobin were 9.9 ± 0.6 and hematocrit of 29.7 ± 1.9. 26.3% of patients had a post-transfusion complication.

On the other hand, 19.5% of women and 20% of men were already anemic when admitted to the hospital.

Anemic women required 7.6 times more transfusions than non-anemic, while anemic men required 12.38 times more transfusions than non-anemic men. Age, presence of coronary artery disease, and chronic anemia have been found to be factors increasing the risk of post-transfusion complications. Finally, urgent and unplanned surgeries are 2.9 times more likely to cause post-transfusion complications.

Conclusion

This study therefore confirms that anemic patients are more likely to receive perioperative blood transfusions. Consequently, in order to reduce blood transfusion and its complications, it would be beneficial primarily to diagnose and treat anemia preoperatively. Other transfusion-saving strategies could also be useful in the setting of surgical bleeding, such as the use of tranexamic acid and different autologous transfusion methods like the cell saver.
Analysis of factors driving water main breaks across 13 Canadian utilities
Authors: Gharaati Sadaf , Dziedzic Rebecca
Published: March 2024

Deterioration of water infrastructure is a global challenge that jeopardizes water system ability to deliver water safely. While various factors affect watermain failure, previous studies have focused on common pipe attributes or general protection strategies. The main objective of this study is to examine the relationship between pipe break characteristics and system properties. Comprehensive data from thirteen Canadian water systems (over 60,000 failures) are examined with correlation and chi-squared analyses. Joint and fitting failures are most likely for pipes aged 20 years or less, and universal joints are most associated with joint failure. Pipes in clay and sand soils are more likely to break due to improper bedding and differential settlement, respectively. Furthermore, in the summer, accidental breaks of asbestos cement pipes are more likely, as are failures of pipes with collar joints and coal tar lined pipes. By exploring these relationships, the paper provides insights into opportunities for reducing water main failure, through improved design, maintenance and rehabilitation.
Effectiveness of ultra-long-term lithium treatment: relevant factors and case series
Authors: Ferensztajn-Rochowiak Ewa , Lewitzka Ute , Chłopocka-Woźniak Maria , Rybakowski Janusz K.
Published: March 2024

Background

The phenomenon of preventing the recurrences of mood disorders by the long-term lithium administration was discovered sixty years ago. Such a property of lithium has been unequivocally confirmed in subsequent years, and the procedure makes nowadays the gold standard for the pharmacological prophylaxis of bipolar disorder (BD). The efficacy of lithium prophylaxis surpasses other mood stabilizers, and the drug has the longest record as far as the duration of its administration is concerned. The continuation of lithium administration in case of good response could be a lifetime and last for several decades. The stability of lithium prophylactic efficacy in most patients is pretty steady. However, resuming lithium after its discontinuation may, in some patients, be less efficient.

Main body

In the article, the clinical and biological factors connected with the prophylactic efficacy of long-term lithium administration are listed. Next, the adverse and beneficial side effects of such longitudinal treatment are presented. The main problems of long-term lithium therapy, which could make an obstacle to lithium continuation, are connected with lithium’s adverse effects on the kidney and, to lesser extent, on thyroid and parathyroid functions. In the paper, the management of these adversities is proposed. Finally, the case reports of three patients who have completed 50 years of lithium therapy are described.

Conclusions

The authors of the paper reckon that in the case of good response, lithium can be given indefinitely. Given the appropriate candidates for such therapy and successful management of the adverse effects, ultra-long term lithium therapy is possible and beneficial for such patients.
Linking undergraduates’ future work self and employability: a moderated mediation model
Authors: Ma Yaju , Hou Lingyan , Cai Wenjing , Gao Xiaopei , Jiang Lin
Published: March 2024

Background

The career intentions of students play a crucial role in shaping the growth of the hospitality and tourism industry. Previous research underlines the significance of future work self in predicting outcomes related to one’s career. However, there is limited knowledge regarding the precise ways, timing, and conditions under which the future work self of undergraduate students can enhance their employability.

Methods

This paper aims to address the existing research gap by employing career construction theory and self-determination theory to propose a moderated mediation model—i.e., career exploration serves as a mediator and job market knowledge functions as a moderator in the relationship between future work self and employability. We conducted two independent studies (i.e., an experimental study and a time-lagged field study) to test the proposed model. Specifically, in Study 1 we employed an experimental research design to recruit 61 students majoring in tourism management to participate. They were randomly assigned to two scenarios (future work self: high vs. low), and we manipulated different levels of future work self by means of scenario descriptions. In Study 2, we used the time-lagged research design to collect data via submitting questionnaires among 253 Chinese undergraduates who majored in hospitality and tourism at a university in the middle area of China.

Results

The results indicate a positive correlation between undergraduates’ future work self and their employability. Furthermore, this relationship is mediated by a mediator of career exploration. It is important to note that this mediating relationship is also contingent upon the moderator variable of undergraduates’ job market knowledge when considering the impact of career exploration on employability.

Conclusion

The findings contribute to enriching the current understanding of the positive effects of future work self on undergraduates’ desirable outcomes in employability.
Actions speak louder than words: modifications of the applied academic books and their reflections on students’ academic success, academic enjoyment, and academic resilience
Authors: Matar Hasan Alharbi Wael
Published: March 2024

Innovation is the process of renewing and updating a domain, a product, or a service by introducing new methods, introducing new techniques, or generating effective concepts to produce new value. Considering universal as well as local books, a teacher may find some sections that need modifications and supportive sections. These changes may have an impact on language learners’ emotional and/or cognitive development. The purpose of this research was to shed light on the use of creative activities and their consequences on academic enjoyment, academic resilience, and academic performance. To that purpose, two groups of EFL (English as a foreign language) learners from Saudi Arabia (public schools) participated in this research and were requested to take pre-and post-tests to assess their level of academic engagement, academic resilience, and academic performance in language skills. According to the data analysis via the Multivariate Analysis of Variance (MANOVA), the experimental group outperformed their counterparts in the control group in terms of academic enjoyment, resilience, and academic performance due to considered modifications in the applied academic books. The study’s pedagogical ramifications are highlighted in the conclusion.
Assessment of perineural spread in advanced cutaneous squamous cell carcinomas treated with immunotherapy
Authors: Cavanagh Karda , McLean Luke S. , Lim Annette M. , Cardin Anthony , Levy Sidney M. , Rischin Danny
Published: March 2024

Background

Cutaneous squamous cell carcinoma (CSCC) has a propensity for perineural spread (PNS) which is associated with poorer treatment outcomes. Immunotherapy is the new standard of care treatment for advanced CSCC resulting in durable responses. PNS is not captured by traditional response assessment criteria used in clinical trials, e.g. RECIST 1.1, and there is limited literature documenting radiological PNS responses to immunotherapy. In this study we assess PNS responses to immunotherapy using a modified grading system.

Methods

This is an Australian single-center retrospective review of patients with advanced CSCC who were treated with immunotherapy between April 2018 and February 2022 who had evidence of PNS on pre-treatment magnetic-resonance imaging (MRI). The primary outcome was blinded overall radiological response in PNS using graded radiological criteria, post-commencement of immunotherapy. Three defined timepoints (< 5 months, 5–10 months, > 10 months) were reviewed. Secondary outcomes included a correlation between RECIST 1.1 and PNS assessments and the assessment of PNS on fluorodeoxyglucose (FDG)-positron emission tomography (PET)/computed tomography (CT).

Results

Twenty CSCC patients treated with immunotherapy were identified. Median age was 75.7 years and 75% (n = 15) were male. All patients had locoregionally advanced disease and no distant metastases. Median follow-up was 18.5 months (range: 2–59). 70% (n = 14) demonstrated a PNS response by 5 months. Three patients experienced pseudoprogression. One patient had PNS progression by the end of study follow up. RECIST 1.1 and PNS responses were largely concordant at > 10 months (Cohen’s Kappa 0.62). 5/14 cases had features suspicious for PNS on FDG-PET/CT.

Conclusions

PNS response to immunotherapy can be documented on MRI using graded radiological criteria. High response rates were seen in PNS with the use of immunotherapy in this cohort and these responses were largely concordant with RECIST 1.1 assessments. FDG-PET/CT demonstrated limited sensitivity in the detection of PNS.
Optimizing organically nano-fabricated Ni metal complexes for enhanced antioxidant and anticancer activity using response surface methodology
Authors: Aleti Swathi , Belwal Savita , Medala Mukunda Vani
Published: March 2024

Background

Researchers, prompted by the toxicity and side effects associated with cisplatin, are exploring alternative approaches for developing transition metal-based anticancer agents. Employing a green biochemical approach, we transformed Nickel pyridine dicarboxylic acid compounds into the nanoscale using the aqueous extract of Macrotyloma uniflorum (horse gram).

Results

Characterization of the biosynthesized nanoparticles involved electronic and IR spectroscopy. A scanning electron microscope revealed a predominant spherical shape for most Nickel nanoparticles (Ni-NPs), with XRD patterns indicating particle sizes ranging from approximately 30–150 nm. The nanoparticles were evaluated for their free radical scavenging efficiency and in vitro anti-malignant properties against HeLa and A549 cancer cell lines. Numerical optimization of the DPPH and MTT assays was conducted using response surface methodology (RSM), focusing on the effects of 3,4-pyridine dicarboxylic acid (ML1), 2,4-pyridine dicarboxylic acid (ML2), nickel nanoparticles concentration, and temperature. In this investigation, the incorporation of Horse Gram seed extract (Macrotyloma uniflorum) has unveiled its abundance in phenolic and flavonoid compounds, widely acknowledged for their robust antioxidant activity in the existing literature.

Conclusion

The present study highlights the potential for refining the bio-toxicity and biochemical attributes of Ni-NPs to pave the way for a new generation of versatile anticancer agents with clinically established efficacy. Notably, the anticipated data closely corresponds with experimental outcomes, reinforcing the trustworthiness and validity of the RSM model for examining anticancer and antioxidant properties in this context. ML2 exhibited heightened antioxidant and anticancer activities in comparison to ML1 nanoparticles.

Graphical abstract
Adapting a coach-assisted web-based intervention for parents of adolescents who refuse school: qualitative study with users of the Partners in Parenting Plus programme
Authors: Smout Anna , Melvin Glenn , Jorm Anthony , Yap Marie B. H.
Published: March 2024

Background

School refusal is a heterogenous problem which typically emerges in adolescence and co-occurs with internalising disorders. A substantial proportion of adolescents do not respond to existing treatment modalities; thus, novel, effective intervention options are needed. Partners in Parenting Plus (PiP+) is a coach-assisted, web-based intervention designed to empower parents to respond to adolescent internalising disorders.

Aims

To conduct a process evaluation of PiP+ and identify programme adaptations required to meet the needs of parents of adolescents who refuse school.

Method

Semi-structured interviews were conducted with 14 Australian mothers who had: (a) received the PiP+ programme (not tailored for school refusal) during a prior research trial; and (b) reported that their adolescent was refusing school during their participation in PiP+. Inductive thematic analysis was used to analyse interview transcripts.

Results

Participants were 41–53 years old (M = 47.8) and parenting adolescent children aged 14–17 years (M = 14.9). Three themes illustrated how PiP+ features met or could better meet the needs of parents of adolescents who were refusing school: (a) feeling heard, supported and respected; (b) relevance to me and my context; and (c) seeing positive changes. Participants had favourable views of PiP+, especially coached components. Participants requested programme enhancements to better meet the needs of parents of neurodiverse adolescents and discussed the impact of cumulative help-seeking ‘failures’ on self-efficacy and locus of control.

Conclusions

PiP+ was highly acceptable to the majority of parents navigating the issue of school refusal. This has implications for the enhancement of coach-assisted parenting interventions and the context-specific adaptation of PiP+ for school refusal.
Internal Mammary Node Irradiation Debate: Case Closed? Not Yet, and Maybe Never
Authors: Recht Abram
Published: March 2024

The IMN debate is still open and may never be closed for reasons outlined in this Comments and Controversies piece.
Adiponectin Inhibits the Progression of Obesity-Associated Papillary Thyroid Carcinoma Through Autophagy
Authors: Li Changlin , Zhang Jiao , Dionigi Gianlorenzo , Liang Nan , Guan Haixia , Sun Hui
Published: March 2024

Context

Obesity is a risk factor for the development of papillary thyroid cancer (PTC). However, the molecular mechanisms by which obesity promotes PTC are unclear.

Objective

This study aims to identify adipokines that are linked to PTC progression.

Methods

An adipokine antibody array was used to determine the serum levels of 40 adipokines in normal-weight and obese PTC patients. Enzyme-linked immunosorbent assay was used to determine the serum levels of adiponectin. Recombinant human adiponectin was produced by human adipose-derived stem cells and used to treat PTC cells. Cell proliferation and migration were evaluated using the CCK8 and Transwell assays. Bioinformatics analysis was used to predict mechanisms by which adiponectin affects PTC.

Results

Adipokines differentially expressed between normal-weight and obese patients showed a gender-dependent pattern. Obese PTC patients had a significantly lower serum adiponectin level than normal-weight patients, especially in female individuals. Adiponectin levels were negatively correlated with aggressive features of PTC, including tumor diameter > 1 cm, extrathyroidal extension, and lymph node metastasis. Recombinant human adiponectin inhibited the proliferation and migration of human PTC cells in vitro. Bioinformatics analysis identified adiponectin receptor 2 (ADIPOR2) and the autophagy pathway as possible mediators of adiponectin function in TC. In vitro experiments confirmed that adiponectin activated autophagy in PTC cells. These findings shed new lights into the role and mechanisms of adiponectin in TC pathogenesis.

Conclusion

Adiponectin is involved in development of obesity-related PTC. Adiponectin can directly inhibit thyroid cancer growth and metastasis through the autophagy pathway.
100 What Are We Transfusing? A Prospective Trial Evaluating the Quality of Intraoperatively Salvaged Red Blood Cells in Spinal Deformity Surgery
Authors: Kurland David B. , Alber Daniel Alexander , Lau Darryl
Published: March 2024

INTRODUCTION:

Intraoperative RBC salvage (aka Cell Saver) is widely employed in spinal deformity surgery. Unlike other surgical subspecialities wherein blood is immediately salvaged (with low potential RBC injury), modern approaches to spine surgery inherently result in collection of blood exposed to high-heat electrocautery, prolonged stasis, and abrasive pharmaceuticals, potentially resulting in RBC injury. However, this has not been studied in a scientific manner.

METHODS:

Patients undergoing spinal deformity surgery with Cell Saver were prospectively enrolled (N = 86). Comparison blood samples include baseline (arterial-line), allogenic (blood bank), and salvage (Cell Saver transfusate). Qualitative laboratory measures of RBC health and hemolysis were collected. Morphological assessment utilized Stimulated Raman Histology (SRH) and artificial intelligence based machine-learning algorithm. Functional RBC evaluation was measured via ektacytometry.

RESULTS:

Salvage blood differed significantly from baseline and allogenic blood, including an unpredictable range of RBC density (2.11-9.52 x 1000/uL), and significantly lower MCV (smaller RBCs) vs. baseline and allogenic samples (p = 0.015 and 4.05E-8, respectively). SRH revealed a high proportion (30.7%) of often irreversibly injured acanthocytes (shrunken and irregularly spiculated RBCs). Ektacytometry revealed that salvaged RBCs were poorly deformable and had impaired relaxation kinetics. Salvage blood samples had significantly higher intracellular components indicating active lysis: potassium (p = 0.019 and 8.2E-16), LDH (p = 3.3E-11 and 1.66E-6), and free-hemoglobin (p = 4.87E-7 and 0.001). The salvage blood mean hemolysis index (HI) was significantly higher than baseline (155x, p = 1.1E-10) and allogenic blood (7.23x, p = 2.29E-5).

CONCLUSIONS:

Intraoperative salvaged blood is composed of high proportions of irreversibly injured RBCs with HI even exceeding levels suitable for transfusion by US FDA and Council of Europe standards, properties that may decrease the suitability of salvaged RBCs as a blood replacement. Collection of postoperative laboratory data and perioperative outcomes are currently underway.
1074 A Prospective, Post Market, Multi-center, Open Label, Non-randomized Clinical Study of the Efficacy of Using a Cellular Bone Allograft (CBA) in Lumbar Fusion Surgery
Authors: Gunter Chris , Wind Joshua James
Published: March 2024

INTRODUCTION:

Autologous bone grafting contains the osteoconductive, osteoinductive and osteogenic elements essential for bone healing in patients at a high-risk for nonunion. There is a lack of prospective lumbar fusion studies with comprehensive and objective outcome assessments that utilize alternatives to iliac crest bone grafting.

METHODS:

This analysis includes subjects with complete clinical and radiographic outcomes at 12-months (n = 221), and 24-months (n = 199) follow-up. Fusion was determined by independent review, characterizing motion (=3° and =3mm) from flexion/extension X-rays, AND the presence of bridging bone via CT.

RESULTS:

The mean age of the study cohort was 58.8 years with 63% being female, and a mean BMI of 30.7. Regarding the subjects reporting of risk-factors to bone healing (e.g., multilevel disease, BMI, nicotine use, diabetes), 86.5% of subjects reported at least a single risk factor, with 49% (n = 99) of subjects reporting multiple risk-factors to bone healing. Fusion success rates were 91.4% (202/221) at 12-months, and 91.9% (183/199) at 24-months. Patient reported outcomes included VAS Back and Leg Pain, ODI, and EQ-5D. Mean ODI significantly improved by 22.1 (p < 0.001) and 22.7 (p < 0.001) points from baseline at 12 and 24-months respectively. Back pain scores decreased significantly from baseline: 57.47 (28.62) to 18.46 (24.86) at 12 months, and 12.02 (21.01) at 24 months. VAS leg pain also significantly decreased from baseline to 12 and 24 months, with an overall decrease in mean score of 27.54 and 32.09 respectively.

CONCLUSIONS:

These study findings provide additional support for the viability and efficacy of CBAs in spinal fusion. The fusion rates observed in this study are comparable to ICBG fusion rates reported in the literature.
1077 Operative Management and Outcomes in Spinal Hemangioblastoma: A Multi-institutional Case Series of 59 Patients
Authors: Blitz Sarah , Friedman Gabriel , Coumans Jean-Valery , Chi John H. , Shin John H. , Curry William T. , Barker Fred , Chapman Paul H. , Chiocca E. Antonio , Borges Lawrence F.
Published: March 2024

INTRODUCTION:

Hemangioblastoma is a rare benign neoplasm that accounts for 2-5% of all spinal cord tumors and is associated with von-Hippel Landau (VHL) disease in about 25-30% of patients. Symptomatic spinal hemangioblastomas are typically managed with en bloc microsurgical resection, but the infrequent nature of these lesions has limited the detailed characterization of reported management and surgical outcomes in the literature.

METHODS:

We retrospectively reviewed all patients with pathology-proven spinal hemangioblastoma. We collected information about demographics, preoperative symptoms and imaging, intraoperative characteristics, and postoperative course. We analyzed what variables influence postoperative changes in motor scores and McCormick scores.

RESULTS:

We included 59 patients (35 sporadic, 24 VHL). The average age of diagnosis was 48.7 (± 16.1) for sporadic tumors and 35.1 (± 12.6) for those associated with VHL (p = 0.001). Most tumors were cervical (46.6%) or thoracic (34.5%) and both intradural (93.2%) and intramedullary (71.2%). Most patients (69.5%) had multiple spinal tumors. The average lesion volume was 0.98 (± 1.1) cm3. The average symptom duration before surgery was 24.7 (± 73.2) months. Adjuvant therapies included radiation (6.8%) and chemotherapy (1.7%). At 1 month postoperatively, 4.4% had motor loss in any muscle group and 31.1% had motor gain, while 18.6% had a decreased McCormick score and 28.8% had an improved score at 1 month. While 72.9% of patients had numbness/paresthesia preoperatively, only 59.3% did at 1 month. Duration of pre-operative symptoms and time from diagnosis to surgery were not found to influence outcomes.

CONCLUSIONS:

Overall, surgical planning should be guided by symptom management. In this population, duration of preoperative symptoms and timing of surgery did not influence post-operative functional outcomes.
1226 Early Versus Delayed Fractionated Stereotactic Radiotherapy for Nonfunctioning Pituitary Adenoma
Authors: Sathe Anish , Siu Alan , Kang KiChang , Kayne Allison , Vinjamuri Shreya , Kelly Patrick David , Shi Wenyin , Evans James J. , Farrell Christopher James
Published: March 2024

INTRODUCTION:

Stereotactic radiosurgery (SRS) can be used to treat residual or recurrent pituitary adenomas with good control rates. Fractionated stereotactic radiotherapy (FSRT) is a viable alternative with similar outcomes. It is currently unknown whether FSRT should be performed early for residual tumor or delayed until progression occurs.

METHODS:

A retrospective review of patients who underwent FSRT for a NFPA between January 2004 to December 2022 at a single institution was performed. We compared the endocrinologic, ophthalmologic, and radiographic outcomes in FSRT delivered as ADJ and PRG treatment.

RESULTS:

75 patients were analyzed, with a median follow-up of 53 months. FSRT was administered to 35 and 40 patients as ADJ and PRG, with a median time to treatment of 5.5 and 40 months, respectively. The tumor control rate was 94.3% for ADJ and 95.0% for PRG. Treatment resulted in four (11.4%) versus seven (17.5%) new endocrinopathies and two (5.7%) versus one (2.5%) new visual deficits for ADJ versus PRG. A survival analysis of time-to-new endocrinopathy showed no difference between the two cohorts. Median time from surgery to new endocrinopathy was 15.5 months for ADJ and 102.0 months for PRG (p = 0.02). The rate of new endocrinopathy at five years was 22.2% in for ADJ and 18.8% for PRG (p = 0.80).

CONCLUSIONS:

FSRT is effective in treating NFPA for residual and progressive tumors, with excellent tumor control rates comparable to SRS and a low risk of developing new endocrinopathies and visual deficits. The delayed treatment in the PRG cohort resulted in a greater duration until the development of a new endocrinopathy, suggesting that observation followed by FSRT on tumor progression may delay the onset of hypopituitarism while maintaining similar effectiveness in tumor control.
1247 Bridging the Gap: ALIF Outshines TLIF in Radiographic Reduction of L5-S1 Spondylolisthesis
Authors: Baig Ammad , Gassie Kelly , Monsour Molly , Carballo Cesar , Alayli Adam , Lockard Gavin , Gordon Jonah , Liaw Deborah , Pressman Elliot , Hidalgo Adolfo , Alikhani Puya
Published: March 2024

INTRODUCTION:

Both the ALIF and TLIF are established surgical approaches for treating Grade 1 or 2 L5-S1 spondylolisthesis. Additionally, each procedure poses different complication profiles. There is a rising debate regarding ALIF versus TLIF regarding multiple outcomes including reduction of spondylolisthesis, thus, we aimed to compare our rates of radiographic reduction.

METHODS:

We conducted a retrospective review of isolated L5-S1 TLIF or ALIF surgeries at our tertiary care center from 2012-2022. These cases were reviewed for demographics, follow-up, preoperative parameters, surgical characteristics, postoperative parameters, radiographic outcomes, reduction rates and complications encountered. The inclusion criteria were minimum age of 18 years and a grade 1 or 2 spondylolisthesis at L5-S1 treated with ALIF or TLIF. We excluded patients with previous instrumentation, trauma, infection, and no spondylolisthesis.

RESULTS:

Of the 156 patients screened, 98 patients were specifically treated for this condition. The ALIF group (n = 40) had a higher rate of complete reduction of spondylolisthesis (90%) compared to the TLIF group (n = 58) (62.1%, p = 0.008). The TLIF group had a higher rate of partial reduction (84%, n = 21) compared to the ALIF group (16%, n = 4). Gender distribution differed significantly between the groups, with the ALIF group comprising 30% males and 70% females, while the TLIF group included 62.1% males and 37.9% females (p = 0.004). Baseline radiographic measures revealed a significant difference in Sagittal Vertical Axis (SVA), with the ALIF group exhibiting a lower average SVA (1.1 ± 3.3) compared to the TLIF group (4.3 ± 2.5, p = 0.005).

CONCLUSIONS:

Although further research is required, when discussing options with patients regarding surgical approaches for Grade 1-2 spondylolisthesis, ALIF demonstrates higher radiographic reduction rates than TLIF at L5-S1.
138 Inflammatory Neuropathy in the Military: Effects on Readiness and Retention
Authors: Scanlon Michaela Marie , Woodle Samuel , Puffer Ross
Published: March 2024

INTRODUCTION:

Neuralgic amyotrophy (NA), or Parsonage-Turner Syndrome, is a complex, multifocal presumed inflammatory disorder of the peripheral nervous system. Presentation varies widely though it classically presents following a precipitating event and begins with a period of sudden onset pain followed by functional loss and atrophy. Prognosis is generally favorable with recovery rates near 80% by 2-3 years. Currently, no data exists on the natural history or surgical management of NA in the active duty (AD) military population, who are subject to uniquely physical work demands. As such, the impact of NA on military readiness and retention remains poorly understood.

METHODS:

AD service-members with a clinic ICD-10 diagnosis of NA were identified from the MHS medical record between the years 2011-2022 and data were obtained retrospectively through individual chart review.

RESULTS:

Over an eleven-year period, forty-one active duty patients were identified (27 males, 12 females, average age 39.6) with an ICD-10 diagnosis of NA. Average time to diagnosis from symptom presentation was 152 days (SD 177). Workup included EMG/NCS in nearly all patients, but advanced imaging in only 9/41 (22%). Ten patients underwent surgical intervention (7 nerve transfers, 1 neurolysis only, 1 tendon transfer, 1 cervical spine decompression). Full recovery was observed for 13/41 (32%) patients while 26/41 (63%) gained only partial improvement (two with unknown recovery/lost in follow-up). Only 1/10 (10%) surgical patients had full recovery. Eight patients underwent a medical board evaluation and were discharged from military service (20%).

CONCLUSIONS:

Neuralgic amyotrophy is a complex disease with a prolonged recovery course that can impact military readiness and active duty retainment.
151 Exceptional Responders to Base Excision Repair (BER) Inhibition for Recurrent Glioblastoma Display Enrichment for DNA Damage Response Pathways: RNA Sequencing Analysis From a Multicenter Trial
Authors: Ozair Ahmad , Drappatz Jan , Ye Xiaobu , Berens Michael , Peng Sen , Rath Sanhita , Dhruv Harshil , Walbert Tobias , Holdhoff Matthias , Lesse Glenn , Cloughesy Timothy F. , Sloan Andrew E. , Couce Marta , Peereboom David M. , Nabors Burt , Wen Patrick , Rogers Lisa R. , Grossman Stuart , Ahluwalia Manmeet
Published: March 2024

INTRODUCTION:

Therapies for glioblastoma recurrence after surgery and chemoradiation are warranted. TRC102 (methoxyamine), a small molecule DNA base-excision repair (BER) inhibitor, reverses temozolomide (TMZ) resistance in preclinical glioma models. We had investigated efficacy of TRC102+TMZ for recurrent glioblastoma (rGBM) through multicenter trial.

METHODS:

A two-arm, two-stage, non-randomized, Phase II trial of TRC102+TMZ for adults with rGBM was conducted. Arm 1 included bevacizumab-naive patients at first recurrence, with primary aim of estimating response rates using RANO criteria. If sufficient activity was identified, arm 2 was planned in bevacizumab-refractory patients. Secondary aims were to determine overall survival (OS), progression-free survival (PFS), PFS at six months, and toxicity using CTCAE v4.0. Exploratory aims were correlating clinical outcomes with MPG expression and MGMT methylation. Differential gene expression profiling was analyzed using DESeq2 GSVA (RRID:SCR_015687) and transformed into enrichment scores for 'hallmark of DNA repair' pathways from Molecular Signatures Database (MSigDB, RRID:SCR_016863) to assign mechanistic signatures of therapeutic vulnerability.

RESULTS:

Arm 1 enrolled 19 patients with median of two treatment cycles, but objective responses were not observed. Hence, arm 2 did not open. Median OS was 11.1 months (95%CI 8.2-17.9). Median PFS was 1.9 months (95%CI 1.8-3.7). MGMT promoter was unmethylated in 14/19 patients, and MPG expression was present in 8/14 cases with available tumor tissue. MGMT methylation and MPG non-expression were associated with better OS and PFS. However, two ‘exceptional responders’ had PFS = 11 months, with MGMT methylated and MPG expressed. RNA sequencing of their tumor tissue demonstrated significant enrichment for DNA damage response (DDR) pathways (MSigDB), chromosomal instability gene signatures (CIN70,CIN25), and proliferative gene signatures (PCNA25).

CONCLUSIONS:

rGBM patients with elevated levels of MPG and DDR molecular signature may have impaired BER and respond better to TRC102+TMZ.
159 PD-1 Agonism as a Strategy to Prevent Neuroinflammation After Acute Large Vessel Occlusion
Authors: Kim Jennifer E. , Lee Ryan P. , Yazigi Eli , Feghali James , Atta Lyla , Pant Ayush , Levitan Idan , Xu Risheng , Patel Kisha K. , Kannapadi Nivedha , Shah Pavan P. , Kim Eileen , Caplan Justin M. , Fernando Gonzalez , Huang Judy , Lim Michael , Tamargo Rafael Jesus , Koehler Raymond , Janzie Lauren , Robinson Shenandoah , Jackson Christopher Mitchell
Published: March 2024

INTRODUCTION:

Stroke is a leading cause of death and long-term disability worldwide. Acute ischemia results in a profound inflammatory response that is counterproductive to short- and long-term recovery. Programmed Death Protein 1 (PD-1) is an immune checkpoint that has been shown to be upregulated after acute cerebral injury, and—upon binding its ligand PD-L1—negatively regulates immune cells to limit the inflammatory response.

METHODS:

C57BL/6J mice underwent middle cerebral artery occlusion (MCAO) and were randomized into three arms: (1)sham surgery, (2)MCAO control, and (3)MCAO+PD-L1. Survival, brain water content, and volumetric MRI analysis of cerebral edema were measured. Brains were analyzed by flow cytometry to quantify PD-1 expression on infiltrating immune cells. Peripheral blood was harvested for single-cell RNA-sequencing. Blood from stroke patients was collected, and the frequency of PD-1+ monocytes was correlated to clinical outcomes.

RESULTS:

PD-L1 significantly decreased brain edema as measured by brain water content (p = 0.0277) and high-resolution MRI (p < 0.0001), and improved overall survival (p = 0.0022). PD-1+ monocytes are upregulated in the ischemic hemisphere, and appear to be critical mediators of edema. PD-L1 treatment decreased PD-1+ monocyte infiltration , while global PD-1 (PD-1-/-) and myeloid-specific knockout of PD-1 (PD-1f/fLysMcre) abrogated the treatment effect on edema. Single-cell RNA sequencing and differential expression analysis of peripheral monocytes revealed downregulation of multiple pro-inflammatory pathways in the treated mice versus the controls. Human correlative studies confirmed that PD-1+ monocytes were present in the peripheral blood of MCA stroke patients, and the frequency of this cell population correlated with post-stroke cerebral edema.

CONCLUSIONS:

Our results support PD-L1 as a novel therapeutic strategy for neuroinflammation and cerebral edema after acute ischemic stroke.
160 Gamme Knife Radio Surgery for Cerebral Arteriovenous Malformation (AVM) in Children: A Systematic Review and Meta-analysis of Clinical Outcomes
Authors: Florez-Perdomo William , Moscote-Salazar Luis Rafael , Agrawal Amit , Janjua Tariq , Chavda Vishal , García-Ballestas Ezequiel , Abdulla Ebtesam
Published: March 2024

INTRODUCTION:

As radiosurgical devices are becoming more commonly used and applied to treat cerebral arteriovenous malformations (cAVMs), there is a growing concern about whether the outcomes of radiosurgery might differ between children, adolescents, and adults due to the distinct characteristics of cAVMs in these age groups.

METHODS:

Search: A search for RCT, not RCT, prospective and retrospective cohort studies in PUBMED; SCOPUS; Central Cochrane Registry ofControlled Trials (The Cochrane Library); MEDLINE; EMBASE (Ovid); CINAHL. The search strategy include subject headings (MeSH) and text words connected with Booleans term. Population: Children (younger than 18 years old) with Cerebral Arterio-venous Malformation (AVMs). Intervention: Gamma Knife radiosurgery (GKS). Outcomes: Primary Outcome: Mortality to end of Follow-up and Surgery successfull determined by the percentage of obliterated AVMs. Secondary Outcome: New Neurological deterioration and Post-Radiosurgery intracranial hemorrhage.

RESULTS:

21 studies with 2142 children who had Gamma knife surgery for cerebral arteriovenous malformations were found for this systematic review. For children with cerebral AVMs treat with GKS, the death rate was 0.725% (95% CI 0.411%-1.126%; I2 = 0%) while the success rate of gamma knife radiosurgery was 71.74% (95% CI 65.716%-77.211%; I2 = 88.13). The rate of complications, such as the rate of new neurological deficits, was 2.57% (1.43% to 3.89%; I2 = 66.78%), and the postoperative intracranial bleeding rate was 2.463% (1.348% to 3.9%; I2 = 70.14%).

CONCLUSIONS:

Gamma Knife radiosurgery is a safe and effective treatment option for cerebral arteriovenous malformations, with high surgical success rates, low mortality, and low complication rates. However, further high-quality case-control studies are needed to evaluate its long-term efficacy and safety.
175 A Patient Prioritization Tool for Non-elective Spine Surgeries: Improving Patient Outcomes and Reducing Adverse Events in a Level-1 Trauma Center
Authors: Rodriguez Beato Freddie Y. , Soufi Khadija , Ebinu Julius O.
Published: March 2024

INTRODUCTION:

The ability to provide comprehensive care at a level 1 trauma center has become challenging, especially considering the impact of COVID on healthcare. These resource-intensive challenges have been exacerbated by provider burnout and a shortage of healthcare providers. In a high-volume tertiary care center, these factors have led to delayed access to care, and potentially an increased incidence of adverse outcomes for non-elective surgical patients. As health systems learn to adapt to these challenges, developing protocols or tools to prioritize patients is paramount for sustainable healthcare systems.

METHODS:

A database review of all non-elective surgeries at a single level 1 trauma center.

RESULTS:

A total of 2,088 surgeries were analyzed and 764 (36%) of surgeries were delayed. There was an increase in the prevalence of delays following the start of COVID-19 (33% to 37%), especially amongst the patients who did not require emergent surgery (<12 hours) (51% vs 38%, p < 0.0001). The average time delay to surgery increased from 54.5 hours to 168 hours peaking at 312 hours mid-pandemic. The prevalence of any complication for all patients was 13.3%, including 1.2% mortality rate, 8.1% readmission rate within 90 days, 0.6% infection rate and prolonged LOS (10.2 vs 9.2 days). Amongst the patients with surgical delays, there was a statistically higher mortality rate (3% vs 1%, p-value < 0.05), complication rate (34.7% vs 13.1%, p < 0.0001) and readmission rate (23% vs 8%, p < 0.0001).

CONCLUSIONS:

An increase in delay for non-elective spine surgery led to increased hospital resource utilization, higher complication and readmission rates, and higher mortality rates in a level-1 trauma center.
181 Initial Experience With Sonodynamic Therapy Using Low-Intensity Focused Ultrasound and ALA for Pediatric Patients With Diffuse Intrinsic Pontine Glioma
Authors: Patel Nirali , Chesney Kelsi M. , Bryant Jean-Paul , Stabingas Kristen , Packer Roger , Kilburn Lindsay , Sheridan Adriana Fonseca , Keating Robert F. , Syed Hasan R.
Published: March 2024

INTRODUCTION:

Diffuse intrinsic pontine glioma (DIPG) is a devastating pediatric brain tumor with poor prognosis. Aminolevulinic acid (ALA) sonodynamic therapy (SDT) is a non-invasive strategy where tissues sensitized with ALA are exposed to MR-guided focused ultrasound (MRgFUS). Preclinical studies have demonstrated significant slowing in growth of gliomas and increased survival in animal models.

METHODS:

A Phase1/2 study (NCT05123534, clinicaltrials.gov) in patients with newly diagnosed DIPG is ongoing. MRIs at 24hrs and 1- and 3-months post procedure are obtained to evaluate safety and efficacy. A total of 18-45 patients will be enrolled in 9 different dose-escalation cohorts. The three patients from the first cohort are described below.

RESULTS:

Three patients with DIPGs were treated with 5 mg/kg of ALA and 200 J of MRgFUS in the first cohort. They were aged 5-7 years and 2 were females. They had received radiotherapy 8-10 weeks prior and interval imaging showed no disease progression. The first patient received two treatments with one half of the pons treated during each visit. The other two received one treatment targeting the entire pons. They all tolerated the procedure well. One of the patients noted a transient worsening of his diplopia after the treatment. No significant edema or hemorrhage were noted on postoperative scans obtained within 24 hrs of treatment. MRIs obtained 1- and 3-months after treatment have shown significant decrease in tumor burden in 2 of the patients.

CONCLUSIONS:

The first-in-human experience with a new therapeutic modality for DIPG patients demonstrates safety and efficacy. Future procedures will involve ascending drug and MRgFUS energy dose combinations. The use of focused ultrasound signals an innovative approach for challenging to treat pediatric brain tumors.
192 Feasibility of Magnetic Resonance-Guided Focused Ultrasound Thalamotomy for Essential Tremor Patients With Low Skull Density Ratio
Authors: Ng Patrick , Blitz Sarah , Jie Chua Melissa Ming , Segar David J. , Cosgrove G. Rees
Published: March 2024

INTRODUCTION:

Magnetic resonance-guided focused ultrasound (MRgFUS) is a safe, effective treatment for essential tremor (ET). Skull density ratio (SDR), the ratio between the densities of cancellous bone and cortical bone, affects energy penetration of the skull. Major clinical trials and guidelines have excluded patients with low skull density ratio due to concerns of disrupted treatment, though these patients represent nearly 40% of ET patients.

METHODS:

In this single-surgeon cohort study of prospectively collected and retrospectively analyzed data, we report the characteristics and clinical outcomes of all ET patients with low SDR (<0.40) vs. high SDR (=0.40) treated at Brigham and Women’s Hospital between June 2019 and February 2023. Clinical outcomes were determined by Fahn-Tolosa-Marin (FTM) scores in the affected limb and percentage of patients with clinical improvements.

RESULTS:

Thirty-one patients had low SDR. 239 patients had high SDR. Mean (±SD) SDRs in the low SDR and high SDR groups were 0.36 (±0.02) and 0.51 (±0.08), respectively. There were no significant differences between the two groups in the following characteristics: sex, handedness, duration of tremor, total preoperative Fahn-Tolosa-Marin (FTM) score, intention + posture preoperative FTM score, age at treatment, treatment laterality, and rate of intraoperative complications. While there were significant differences in the clinical outcomes of low SDR vs. high SDR patients on postoperative day 1 (POD1), the clinical outcomes between the two groups were not significantly different at every follow-up time point, including up to three years post-treatment.

CONCLUSIONS:

While clinical outcomes were significantly different on POD1, low SDR and high SDR patients had similar long-term clinical outcomes, suggesting that MRgFUS of ET patients with SDR < 0.40 is feasible and effective.
195 Targeting Thalamocortical Circuits For Closed-Loop Stimulation in Lennox-Gastaut Syndrome
Authors: Warren Aaron , Butson Chris , Hook Matthew , Dalic Linda , Archer John , Macdonald-Laurs Emma , Schaper Frederic , Singh Hargunbir , Johnson Lise , Bullinger Katie , Gross Robert E. , Morrell Martha J. , Rolston John
Published: March 2024

INTRODUCTION:

Lennox-Gastaut syndrome (LGS) is a severe, childhood-onset epilepsy associated with frequent seizures, cognitive impairment, and high burden of care. Electrical stimulation of the thalamus can be an effective treatment for LGS, but complete seizure control is rarely achieved. Outcomes may be improved by stimulating areas beyond the thalamus, including cortex, but the optimal targets are unknown.

METHODS:

Brain network maps from 3 group-level studies of LGS were averaged to define the area of peak overlap: combined electroencephalography-functional MRI (EEG-fMRI) of paroxysmal fast activity, [18F]fluorodeoxyglucose positron emission tomography (FDG-PET) of hypometabolism, and structural connectivity associated with efficacy in a previous trial of deep brain stimulation. The resulting “hotspot” was used as a seed in a normative fMRI connectivity analysis to identify connected networks. Two patients underwent bilateral thalamocortical implantations guided by this hotspot. Simultaneous recordings from cortex and thalamus were analyzed for presence and synchrony of epileptiform activity.

RESULTS:

Peak overlap was in bilateral premotor cortex. Functional connectivity of this hotspot revealed a network of frontoparietal cortex resembling the diffuse abnormalities seen on EEG-fMRI and FDG-PET. Intracranial electrophysiology showed characteristic epileptiform activity of LGS in the cortical hotspot that preceded or co-occurred with similar thalamic activity.

CONCLUSIONS:

Premotor cortex shows peak involvement in LGS, and functional connectivity of this region resembles the wider epileptic brain network. Thus, it may be an optimal target for neuromodulation therapies, including thalamocortical stimulation. Compared to thalamus-only stimulation, addition of this cortical target may allow more rapid detections and responsive stimulations of seizures, and broader modulation of the brain network underlying LGS to achieve greater seizure control.